[Federal Register Volume 59, Number 169 (Thursday, September 1, 1994)]
[Unknown Section]
[Page 0]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-21359]


[[Page Unknown]]

[Federal Register: September 1, 1994]


      
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Part III





Environmental Protection Agency





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40 CFR Part 700, et al.




Microbial Products of Biotechnology; Proposed Regulation Under the 
Toxic Substances Control Act; Proposed Rule
ENVIRONMENTAL PROTECTION AGENCY

40 CFR Parts 700, 720, 721, 723, and 725

[OPPTS-00049c; FRL-4778-4]
RIN 2070-AB61

 
Microbial Products of Biotechnology; Proposed Regulation Under 
the Toxic Substances Control Act

AGENCY: Environmental Protection Agency (EPA).

ACTION: Proposed rule.

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SUMMARY: EPA is proposing this regulation under section 5 of the Toxic 
Substances Control Act (TSCA), 15 U.S.C 2604, to screen microorganisms 
before they are introduced into commerce. Under an interpretation EPA 
issued in 1986 (51 FR 23302, June 26, 1986), ``new'' microorganisms are 
those formed by deliberate combinations of genetic material from 
organisms in different genera. This proposed rule is designed to 
prevent unreasonable risk to human health and the environment without 
imposing unnecessary regulatory burdens on the biotechnology industry. 
This proposed regulation describes notification procedures and 
microorganisms that would be exempt from notification.

DATES: Written comments on this proposed rule should be received by 
October 31, 1994.
    EPA may hold an informal hearing in Washington, DC, if EPA receives 
written requests to hold a public hearing. For further information on 
the hearing, see Unit IV.I. of this preamble. Written requests to make 
an oral presentation should be submitted to the Environmental 
Assistance Division by October 3, 1994 at the address below. Persons 
are advised to call the Environmental Assistance Division after October 
11, 1994 to ascertain if a hearing is to be held, and the date, time, 
and location.

ADDRESSES: Comments on issues concerning this proposed rule should bear 
the docket control number OPPTS-00049C, and should be submitted to the 
following address: Document Processing Center (7407), Office of 
Pollution Prevention and Toxics, Environmental Protection Agency, Rm. 
L-100, 401 M St., SW., Washington, DC 20460.

FOR FURTHER INFORMATION CONTACT: For general information including 
copies of this document and related materials: Susan Hazen, Director, 
Environmental Assistance Division (7408), Office of Pollution 
Prevention and Toxics, Environmental Protection Agency, Rm. EB-44, 401 
M St., SW., Washington, DC 20460, In the USA: (202-554-1404), TDD: 
(202-554-0551). For technical information regarding this document: Paul 
Campanella, Office of Pollution Prevention Toxics (7405), Environmental 
Protection Agency, Rm. E-611, 401 M St., SW., Washington, DC 20460, In 
the USA: (202-260-3725).

SUPPLEMENTARY INFORMATION: The preamble accompanying this proposed rule 
is divided into the following Units:
I. Introduction
    A. Purpose of This Proposed Rule
    B. Role of This Propose Rule in the Federal Coordinated 
Framework for Regulation of Biotechnology
    C. Statutory Framework
II. Structure of This Proposed Rule
    A. Determining Whether Reporting is Required
    B. General Administrative Procedures
    C. Reporting General Commercial Use of TSCA Microorganisms
    D. Reporting R&D Activities for TSCA Microorganisms
III. Rationale for Proposed Reporting Mechanisms
    A. Research for Commercial Purposes
    B. Exemption for Research in Contained Structures
    C. Section 5(h)(4) Exemptions
IV. Other Issues
    A. Microorganisms Covered By This Rulemaking
    B. Listing Microorganisms on the Inventory
    C. SNUR Process
    D. Confidential Business Information
    E. User Fees
    F. Section 8(e) Reporting Requirements
    G. Export Notification and State Preemption
    H. Regulatory Text Overview
    I. Rulemaking Process and Public Hearings
V. Economic Impact and Regulatory Flexibility Analysis
    A. Regulatory Impact Analysis
    B. Request for Comment on Economic Issues
VI. Rulemaking Record and Electronic Availability of Documents
VII. Public Record
VIII. References
IX. Regulatory Assessment Requirements
    A. Executive Order 12866
    B. Regulatory Flexibility Act
    C. Paperwork Reduction Act

I. Introduction

A. Purpose of This Proposed Rule

    This document proposes procedures for EPA to screen new 
microorganisms. EPA's goals in proposing these rules are to take into 
account scientific uncertainties surrounding the behavior of these 
microorganisms and avoid unreasonable risks to health and the 
environment which may be associated with their use, to avoid imposing 
unwarranted costs and restrictions on a promising industry, and to 
establish a flexible review program that can adjust as the technology 
evolves and matures.
    EPA will screen new microorganisms before they are manufactured for 
general commercial use, or in some circumstances used for commercial 
research and development (R&D) purposes, until sufficient familiarity 
is gained with their behavior. As EPA acquires familiarity with new 
microorganisms through reviews or other avenues, EPA expects certain of 
these organisms to become eligible for reduced reporting or to be 
eliminated from screening altogether.
    EPA recognizes the enormous potential of biotechnology to fight 
disease, pollution, and hunger, and to replace some chemicals that are 
harmful to the environment. The realization of these benefits depends 
upon public confidence in the safety of biotechnology. Public 
perception will strongly affect the conduct of field tests and the 
acceptance of commercial applications of biotechnology (Ref. 1). At the 
same time, EPA recognizes the importance of retaining the competitive 
advantage the United States presently maintains in the development and 
application of biotechnology. Recognizing that regulations can affect 
competitiveness and public acceptance either negatively or positively 
(Ref. 2), EPA is proposing rules that it believes balance the needs of 
the public without adversely affecting the capacity for innovation.

B. Role of This Proposed Rule in the Federal Coordinated Framework For 
Regulation of Biotechnology

    This proposed rule implements EPA's program for oversight of 
microorganisms in accordance with the Federal ``Coordinated Framework 
for Regulation of Biotechnology; Announcement of Policy and Notice for 
Public Comment'' which was published by the Office of Science and 
Technology Policy (OSTP) on June 26, 1986 (51 FR 23302, 23313). EPA's 
policies regarding use of its statutes to regulate biotechnology 
products are published in the ``Statement of Policy: Microbial Products 
Subject to the Federal Insecticide, Fungicide, and Rodenticide Act and 
Toxic Substances Control Act'' (``1986 Policy Statement'') which was 
published as part of the Coordinated Framework. EPA is currently 
operating its biotechnology program under the 1986 Policy Statement.
    Prior to the 1986 Policy Statement, EPA issued a ``Proposed Policy 
Regarding Certain Microbial Products'' on December 31, 1984 (49 FR 
50880) (``1984 Proposed Policy Statement''). Subsequent to the 1986 
Policy Statement, EPA issued a notice, entitled ``Biotechnology; 
Request for Comment on Regulatory Approach'' on February 15, 1989 (54 
FR 7027), in order to solicit comments on the direction of EPA's 
program under TSCA. Comments on the 1984 and 1986 documents and the 
February 15, 1989 Federal Register notice are addressed, as 
appropriate, in this preamble.
    On September 7, 1990, EPA convened a subcommittee of its 
Biotechnology Science Advisory Committee (Subcommittee on 
Implementation of Scope) to comment on topics associated with this 
proposed rule. EPA again convened a subcommittee, the Subcommittee on 
the Proposed Biotechnology Rule under TSCA, which met on July 22, 1991. 
Advice from both of these subcommittees has been incorporated as 
appropriate in this preamble, and summaries of subcommittee 
deliberations have been placed in the docket for this rulemaking. This 
proposed rule announced today is intended to describe implementation of 
EPA's program for regulation of microorganisms under TSCA.

C. Statutory Framework

    This Unit describes the TSCA provisions used for this rulemaking.
    1. Jurisdiction. TSCA authorizes EPA to regulate any chemical 
substance, except for certain substances covered by other Federal 
agencies. The Act defines chemical substance broadly enough to cover 
microorganisms. Specifically, section 3(2) of TSCA defines chemical 
substance, in part, as any organic substance of a particular molecular 
identity including any combination of such substances resulting in 
whole or in part from a chemical reaction or occurring in nature.
    a. Organisms are chemical substances. The TSCA definition of 
chemical substance describes any deoxyribonucleic acid (DNA) or 
ribonucleic acid (RNA) molecule, however created, that is a component 
of an organism's genetic material. Similarly, a microorganism is a 
chemical substance, because it is a combination of substances of 
particular identities that occur in nature or occur, in whole or in 
part, as a result of a chemical reaction (Ref. 3). EPA has consistently 
applied this definition to life forms and in the 1984 Proposed Policy 
Statement (49 FR 50886-87) clarified that this interpretation applies 
to microorganisms. While the statutory term ``chemical substance'' has 
been interpreted to include microorganisms, EPA acknowledges that 
microorganisms are not generally referred to as chemicals. Therefore, 
throughout this preamble, the term ``traditional chemicals'' will be 
used to refer to chemical substances other than microorganisms.
    The fact that microorganisms can be considered chemical substances 
under TSCA only establishes EPA authority over them. Implementation of 
that authority requires further action, either to interpret specific 
terms or to issue rules. Discussion of the types of microorganisms 
covered in this proposal can be found in Unit IV.A. of this preamble.
    b. Plants and animals are not subject to this proposed rule. Plants 
and animals could also be chemical substances under TSCA. Nevertheless, 
as a matter of policy, EPA has limited this rulemaking to 
microorganisms, e.g., microalgae of the plant kingdom. Transgenic 
plants and animals are not subject to requirements under this proposed 
rule, either as whole organisms or when their cells or parts of cells 
are cultured in vitro. However, microorganisms into which plant or 
animal gene segments are intentionally incorporated would be considered 
microorganisms potentially subject to TSCA. Traditional chemicals 
extracted from a plant or animal also may be subject to TSCA, as are 
other chemical substances. EPA is reserving authority under TSCA to 
screen transgenic plants and animals in the future as needed.
    c. Microorganisms excluded by statute. The definition of ``chemical 
substance'' in TSCA excludes pesticides, tobacco and tobacco products, 
food, food additives, drugs (including human drugs, animal drugs, and 
animal biologics), cosmetics, and substances that are used as medical 
devices. These substances are regulated under other statutes by the EPA 
Office of Pesticide Programs, the United States Department of 
Agriculture (USDA), or the Food and Drug Administration (FDA).
    Certain microorganisms that are subject to TSCA but are also known 
plant pests are regulated jointly by EPA under TSCA and the USDA under 
the Federal Plant Pest Act. In cases where microorganisms are not known 
to be plant pests, the microorganisms used for TSCA purposes would be 
regulated solely by EPA. However, USDA would become involved if an EPA 
review determined that the microorganism had plant pest qualities.
    d. Microorganisms used as intermediates. Microorganisms may be used 
as intermediates to produce substances that are in turn used as 
products subject to TSCA or other statutes. Under the Federal Food, 
Drug, and Cosmetics Act (FFDCA), intermediates used to make products 
subject to FFDCA are considered to be components of foods, food 
additives, drugs, cosmetics and medical devices, as the case may be. 
Therefore, those microorganism intermediates are excluded from 
regulation under TSCA. All other intermediates, including pesticide 
intermediates, are subject to TSCA jurisdiction. Traditional chemicals 
not excluded from TSCA and produced by microorganism intermediates are 
subject to TSCA section 5. These chemicals produced by microorganisms 
are subject to the same requirements and procedures as chemicals 
produced by other means. EPA discussed its approach to microorganism 
intermediates and their products in its 1984 Proposed Policy Statement 
(49 FR 50887, 50890; December 31, 1984).
    2. Application of TSCA section 5. TSCA gives EPA comprehensive 
authority to regulate chemical substances and mixtures of chemical 
substances under four major provisions. Section 4 authorizes the 
issuance of rules requiring testing of chemicals. Section 6 authorizes 
the Agency to issue substantive regulations to protect against 
chemicals that present an unreasonable risk. Section 7 authorizes 
protection against imminent hazards. EPA has based its biotechnology 
rulemaking efforts on section 5, the other major TSCA provision. 
Section 5 establishes a 90-day process for EPA to screen certain 
chemical substances before they are produced. Within the 90 days 
following receipt of notification, EPA has to decide whether to drop 
the substance from further consideration or to impose controls.
    Section 5(a) allows EPA to require submission of a notification for 
two types of microorganisms, those that are considered ``new'' chemical 
substances and those that will be made for a ``significant new use.'' 
In both cases, notification is not triggered by a determination that a 
risk is present. Risk is fully considered during or after the screening 
process. Those substances defined as ``new chemical substances'' are 
automatically subject to notice requirements. Chemical substances which 
are made for a significant new use are subject to notification when EPA 
issues a rule for the particular substance.
    While the statute TSCA does not distinguish between the form or 
content of the notifications for new substances or new uses, EPA's 
current regulatory program, which is largely applicable to traditional 
chemicals, does. The notification for a new chemical substance is 
called a premanufacture notice (PMN). The notification for a 
significant new use is called a significant new use notice (SNUN). For 
the biotechnology program, however, EPA is proposing to refer to either 
type of notification as a Microbial Commercial Activity Notice or MCAN.
    Notices under section 5(a) are submitted by manufacturers of new 
chemical substances, and by persons who manufacture or process chemical 
substances for a significant new use. TSCA section 3(7) defines 
``manufacture'' to mean import into the United States, production or 
manufacture. Thus, the word manufacture as used in this preamble refers 
to importation and any type of production, as well as to those 
activities that may commonly be considered manufacture. TSCA section 
3(10) defines ``process'' as preparation of a substance, after its 
manufacture, for distribution in commerce.
    a. Distinction between ``commercial purposes'' and ``general 
commercial use.'' TSCA section 5(i) limits section 5 screening to 
activities ``for commercial purposes.'' The term ``commercial 
purposes'' applies to all activities that derive actual or potential 
commercial benefit for persons associated with those activities. This 
includes R&D designed to result in a commercial product, whether or not 
a product is actually developed. A discussion of various options for 
EPA to decide what constitutes commercial purposes under this rule 
appears at Unit III.A.
    These rules propose different review procedures for microorganisms 
used for commercial R&D and for microorganisms that are no longer in 
R&D and are intended for commercial distribution. In order to 
distinguish between commercial R&D and other types of commercial 
activity, EPA is describing use for commercial purposes beyond R&D as 
``general commercial use.''
    b. Definition of ``new.'' The term, ``new chemical substance,'' is 
defined at TSCA section 3(9) as a substance not on the TSCA Inventory 
of Chemical Substances (``Inventory'') manufactured in the United 
States. Compilation and publication of the Inventory is a requirement 
imposed on EPA by TSCA section 8(b). When EPA completes review of a new 
substance, the substance is placed on the Inventory upon EPA's receipt 
of a Notice of Commencement which indicates that production has begun. 
At this point, the substance is no longer new, and subsequent producers 
do not have to submit PMNs.
    EPA has a longstanding policy of not explicitly listing on the 
Inventory unprocessed naturally occurring substances. Instead, these 
substances are considered to be implicitly included on the Inventory 
(see 40 CFR 710.4(b)). Thus, they are not ``new'' and do not require 
PMNs.
    In defining what constitutes an unprocessed naturally occurring 
substance, EPA has distinguished between substances isolated from 
nature using more or less mechanical means and those isolated from 
nature using more sophisticated forms of human intervention, such as 
chemical reactions. The latter substances remove from a natural product 
something that, by itself, does not exist in nature. One example is 
that natural latex extracted from trees is a naturally occurring 
substance, but the rubber formed after chemical coagulants are added is 
not (42 FR 64589, December 23, 1977).
    EPA is retaining for this rulemaking its interpretation of ``new'' 
microorganisms as discussed in the 1986 Policy Statement. Under that 
interpretation, microorganisms resulting from deliberate, intergeneric 
combinations of genetic material constitute ``new'' microorganisms 
subject to PMN requirements. For the purposes of the Policy Statement, 
the Agency defined intergeneric microorganisms as those formed by 
deliberate combinations of genetic material from source organisms in 
different genera. EPA may decide to reconsider its interpretation of 
``new'' microorganism at a later time and in aseparate rulemaking. EPA 
requests comment on whether it should explore alternative 
interpretations of ``new'' microorganism.
    In the 1986 Policy Statement, EPA excluded from the definition of a 
``new'' microorganism, those microorganisms that have resulted from the 
addition of intergeneric material that is well-characterized and 
contains only non-coding regulatory regions such as operators, 
promoters, origins of replication, terminators, and ribosome-binding 
regions. EPA is also proposing to retain this exclusion as part of its 
interpretation of ``new'' microorganism.
    In the course of implementing the 1986 Policy Statement, the Agency 
recognized that it had to develop additional guidance concerning the 
definition of a new microorganism. It became apparent that a policy was 
needed to address certain genetic elements which can be transferred 
between microorganisms of different genera. These are termed mobile 
genetic elements (MGEs) and include plasmids and transposons. EPA 
developed additional guidance concerning whether microorganisms 
modified using vectors that contained MGEs or parts of MGEs were 
considered new. The Agency indicated that the major consideration is 
the source of the original isolation of the MGE. EPA stated that 
microorganisms would be considered ``new'' and thus subject to PMN 
requirements, if the MGE was originally isolated from a microorganism 
in a genus different from the recipient genus. Microorganisms would be 
considered intrageneric, and hence not subject to PMN requirements, if 
the MGE was originally isolated from a microorganism in the same genus 
as the recipient.
    The Agency has adopted this interpretation for reasons of 
regulatory clarity and uncertainty about the possibility of the 
resulting microorganism exhibiting new traits. For example, some MGEs 
may contain genetic material that normally is not expressed in one 
microorganism but, when inserted into another microorganism, may be 
expressed and result in a new trait. Since the Agency plans to continue 
to use the 1986 Policy Statement interpretation of ``new'' to be 
intergeneric microorganisms, the Agency will continue to use this MGE 
guidance to clarify what microorganisms would be subject to TSCA 
section 5 reporting. EPA specifically requests comments on whether the 
MGE interpretation provides appropriate assistance for determining 
whether a microorganism is intergeneric or whether additional 
modifications which would be useful in clarifying which intergeneric 
microorganisms should be reported under TSCA section 5.
    c. Significant new use. EPA determines a use is a significant new 
use by issuing a rule. The rule is called a significant new use rule or 
SNUR. Section 5(a)(2) sets forth some of the relevant considerations 
for issuing a SNUR. The considerations generally include changes in the 
type or form of exposure to a substance. Although EPA is not proposing 
any specific SNURs in this rulemaking, EPA is proposing to set up 
processes for issuing SNURs for microorganisms if needed in the future. 
See Unit IV.C. of this preamble for a discussion of the proposed SNUR 
processes.
    d. Section 5 regulatory mechanisms. If the 90-day period provided 
for review of a PMN or SNUN expires and EPA has taken no action, 
production of the substance may begin. However, within the review 
period, EPA may prevent or limit production of the substance under 
section 5(e) or 5(f). Under section 5(e) EPA may issue an order 
prohibiting or limiting production of a substance, if the Agency 
determines that information is insufficient and the substance may 
present unreasonable risk or its use may result in substantial 
exposure. If the notification submitter objects, the section 5(e) order 
does not take effect and EPA may go to court to obtain an injunction to 
accomplish the same goals as the section 5(e) order.
    Alternatively, if EPA finds that a substance presents or will 
present an unreasonable risk, the Agency may, under section 5(f), go to 
court for an order restricting or prohibiting production or issue an 
administrative order or immediately effective rule to accomplish that 
result.
    If EPA decides subsequent to Inventory listing that further 
oversight is needed, the Agency may use other provisions of TSCA. These 
could include SNURs or other rules that would require testing (TSCA 
section 4), information submission (TSCA section 8) or substantive 
restrictions (TSCA section 6).
    e. Exemptions from the section 5 notification process. Section 5(h) 
provides for certain exemptions from screening. Three are relevant to 
biotechnology. Section 5(h)(1) allows manufacturers or processors of 
substances only for test marketing to apply to EPA for an exemption 
from full notification. Unit II.C.3. of this preamble discusses the 
test marketing exemption (TME) for microorganisms.
    Section 5(h)(3) provides that the screening mechanisms do not apply 
to substances manufactured or processed only in ``small quantities'' 
for R&D, provided that persons engaged in R&D activities for a 
manufacturer are notified of any risks to health associated with the 
substance. Section 5(h)(3) authorizes EPA to define by rule what 
constitutes small quantities and to prescribe the form and manner of 
risk notification. EPA is proposing a small quantities definition that 
is limited to contained structure R&D uses of microorganisms. There 
would be no small quantities exemption for microorganisms introduced 
into the environment during commercial R&D, thus use of such 
microorganisms must be reviewed. This modification is described at Unit 
II.D. of this preamble. The rationale for this modification is 
discussed at Unit III.B. of this preamble.
    Section 5(h)(4) allows EPA to exempt new substances from all or 
part of section 5 screening requirements, if the Agency determines, by 
rule, that such substances will not present an unreasonable risk. EPA 
is proposing to use section 5(h)(4) to exempt certain categories of 
microorganisms from screening as new microorganisms. Additionally, EPA 
is proposing under section 5(h)(4) to allow R&D introductions of 
microorganisms into the environment on the condition that EPA has 
approved them through expedited review of information submitted in a 
TSCA Experimental Release Application, or TERA. The TERA process is 
described in Unit II.D. of this preamble. EPA is also proposing other 
section 5(h)(4) exemptions for specific microorganisms and classes of 
microorganisms as described in Unit II.C. of this preamble. The 
rationale for all exemptions proposed under section 5(h)(4) appears in 
Unit III.C. of this preamble.
    3. Substantial risk notification. Section 8(e) requires reporting 
by manufacturers, processors and distributors who come across 
information that their chemical substance could cause a ``substantial 
risk.'' Section 8(e) is a self-implementing provision of TSCA. Thus, if 
a manufacturer, processor or distributor of a microorganism finds 
applicable information, that information must be submitted to EPA. Unit 
IV.F. of this preamble discusses section 8(e) in further detail.
    4. Applicability of TSCA section 26. Section 26(c) authorizes EPA 
to take any action under TSCA for a category of chemical substances. 
EPA proposes to use this authority extensively in this rule. The 
reasons for grouping microorganisms into categories, which include new 
microorganisms used for R&D and certain new microorganisms manufactured 
for general commercial use, are explained in applicable sections.

II. Structure of the Proposed Rule

    This portion of the preamble discusses the major provisions of 
these rules. The rationale supporting these provisions follows in Unit 
III. Unit II.A. describes how to determine whether reporting is 
required. Unit II.B. describes general administrative procedures that 
would be applicable to all notices submitted. To facilitate 
understanding of this proposed rule, requirements for microorganisms 
manufactured for general commercial use are discussed separately from 
those for microorganisms used for commercial R&D. Unit II.C. describes 
procedures applicable to microorganisms which are manufactured for 
general commercial use. Unit II.D. contains a similar description of 
procedures applicable to microorganisms used for R&D.
    While these regulations are modelled after and incorporate many of 
the procedures in the existing TSCA section 5 screening program for 
traditional chemical substances which EPA has operated for the past 
decade, modifications have been made, as appropriate, to address the 
specific characteristics of microorganisms. In this respect, this 
proposed rule incorporates well-established procedures which EPA has 
adopted in previous rulemakings. The procedures are currently contained 
in the Code of Federal Regulations (``CFR'') at parts 720 
(premanufacture notification) and 721 (significant new use notification 
requirements). EPA has decided, however, to establish a new part in the 
CFR which applies specifically to microorganisms. EPA believes that 
placing regulations affecting microorganisms screened under TSCA 
section 5 in one place, part 725, will be more convenient and 
efficient.
    EPA has only made changes to the procedures in parts 720 and 721 to 
the extent required by unique characteristics of microorganisms. EPA is 
therefore not soliciting comment on the procedures in proposed part 725 
that are incorporated from parts 720 and 721.
    EPA will only consider comments to the extent they address the new 
procedures and requirements in proposed part 725.
    In addition to a preferred approach for certain issues, this 
preamble often contains a discussion of alternatives. EPA solicits 
public comment on the preferred approaches and the alternatives 
discussed in this document. Depending on public comment received on the 
various proposals, any of these alternatives may be adopted in the 
final rules.

A. Determining Whether Reporting Is Required

    Manufacturers or processors would follow the process laid out below 
to determine whether their microorganism is subject to reporting and, 
if it is, how it would be treated under this proposed rulemaking. They 
must first determine whether their microbial products are subject to 
TSCA. Subpart A of part 725 contains the regulations applicable to this 
determination. Many microorganisms are not subject to the requirements 
of this proposed rule, because they are statutorily outside the 
jurisdiction of TSCA. Statutory jurisdiction is discussed in Unit I.C. 
of this preamble.
    1. Determining whether a microorganism is new or subject to a SNUR. 
After manufacturers of microorganisms determine that their products are 
subject to TSCA, they must determine whether the microorganisms are 
new. Section 725.3 defines a new microorganism as one that is not 
included on the Inventory. Microorganisms may be either implicitly or 
explicitly included on the Inventory.
    a. Implicit inclusion. In its 1986 Policy Statement, EPA stated 
that intergeneric microorganisms were the only microorganisms that 
would not be implicitly included on the Inventory. As discussed in Unit 
I.C. of this preamble, EPA will continue to use the 1986 Policy 
Statement interpretation for this rulemaking.
    b. Explicit listing. A microorganism is not new, if it is 
explicitly listed or implicitly included on the Inventory. 
Microorganisms are placed on the Inventory if they have been previously 
manufactured in the United States for general commercial use. EPA 
explicitly lists microorganisms that it has previously reviewed, after 
it is informed that production has begun through receipt of a Notice of 
Commencement of Manufacture (NOC) (see Sec. 725.190). If a 
microorganism is not considered to be implicitly included on the 
Inventory, the public Inventory needs to be consulted to determine 
whether the microorganism is explicitly listed. Microorganisms may also 
be explicitly listed but treated as confidential and not placed on the 
public Inventory.
    c. SNUR listing. After persons determine that their microorganisms 
are included on the Inventory, they must then check to see if the 
microorganisms are subject to a SNUR. Where appropriate, microorganisms 
subject to SNURs will be identified, both on the Inventory and in 
Subpart M of part 725. The SNUR process is discussed in Unit IV.C. of 
this preamble.
    2. Consulting EPA when microorganism identity or use is 
confidential or uncertain. Specific situations arise under these rules 
when persons would need to consult listings of microorganisms to 
determine whether a particular microorganism, or use of a 
microorganism, is subject to reporting. These listings include the 
Inventory; Subpart M of part 725, which lists significant new use 
rules; and Sec. 725.239, which lists certain microorganisms exempt from 
R&D reporting under part 725. The listings are explained in the text of 
the regulation.
    There would be two specific circumstances under which it may not be 
possible to determine whether a particular microorganism is listed. 
First, the actual identity or use may be claimed confidential by a 
person who originally manufactured or processed the microorganism. In 
this case, a so-called generic name or use would appear on the public 
Inventory, and the actual identity or use would be on a confidential 
listing not available to the public. Unit IV.D. on Confidential 
Business Information (CBI) explains the generic name and use. The 
second circumstance would be that a non-confidential identity of a 
microorganism may not be precise enough for a person to determine 
whether it describes a particular microorganism that could be subject 
to reporting. This circumstance may arise because of the imprecision of 
scientific nomenclature in biology, particularly in microbiology, or 
because similarities in modified genetic material may raise questions 
of equivalency (see Unit IV.B.).
    To assist persons in determining their reporting obligations, EPA 
has established a procedure whereby a person may file a submission 
establishing a bona fide intent to manufacture or process a 
microorganism and request that the Agency determine whether that 
microorganism is on the applicable listing. EPA's goal is to respond in 
30 days to the request, informing the requestor whether there is an 
obligation to report under these regulations (see Sec. 725.15). This 
procedure allows EPA to ensure appropriate reporting while maintaining 
the confidentiality of legitimate trade secrets. This is a well-
established procedure in the Agency's current regulations on TSCA 
section 5 reporting (see Secs. 720.25 and 721.11). This preamble will 
note when this process, known as a ``bona fide,'' applies.

B. General Administrative Procedures

    After submitters determine that they have a microorganism subject 
to TSCA section 5, they must determine what type of submission will 
satisfy their reporting obligations. The first decision is whether the 
microorganism will be used for R&D or general commercial use. The 
specifics of the submission and review processes for general commercial 
use and for R&D are covered in Units II.C. and II.D. of this preamble, 
respectively. However, some administrative procedures apply generally 
to all microorganism submissions. Therefore, general administrative 
procedures are discussed in this Unit.
    Subpart B of part 725 contains administrative procedures generally 
applicable to all submissions. Most of these are rather mechanical, 
such as general recordkeeping requirements, procedures for determining 
whether submissions are complete and properly filed, how to determine 
when the Agency will begin the review period designated for a 
particular submission, and under what circumstances the Agency or the 
submitter may suspend, extend, or terminate a review. The more 
important administrative procedures are discussed in this Unit.
    1. Prenotice consultation. EPA recommends that potential submitters 
begin discussions with EPA staff early in the submission planning 
process to identify any special data requests and preliminary concerns 
that may be associated with the microorganism. This may save 
significant time later in the review process. Any meetings and relevant 
written communications may be claimed confidential. Persons who are 
unsure as to whether their microorganisms are subject to any of the 
requirements of part 725 should consult with EPA before preparing any 
submission.
    With reference to R&D, EPA recognizes that research proceeds 
through various stages. Potential submitters may find it advantageous 
to begin discussions with EPA as early as the grant proposal stage, 
even though they would not be required to file a submission under part 
725 until the latter stages of their research program. Early 
consultation with the Agency could assist submitters in the planning 
stages of their research program in addition to providing a smoother 
submission and review process.
    2. Submission process. The general requirements pertaining to the 
submission process are found at Secs. 725.25 through 725.36.
    a. Preparing submissions. The data to be included in submissions 
for microorganisms would be different from those for traditional 
chemicals, because microorganisms may pose different risks than those 
posed by traditional chemicals. To assist persons preparing submissions 
under this proposed rule, EPA has developed a special guidance document 
entitled ``Points to Consider in the Preparation and Submission of TSCA 
Notifications for Microorganisms.'' At this time, a special form has 
not been developed for microorganism submissions. Therefore, persons 
preparing microorganism submissions should follow the format outlined 
in the guidance document. This document is available from the 
Environmental Assistance Division (see the address listed under the FOR 
FURTHER INFORMATION CONTACT Unit).
    The regulatory text describes the type of information that is 
relevant for each specific type of submission. Submitters should submit 
all reasonably ascertainable information which they believe will assist 
EPA in evaluating the microorganisms, including information not 
specifically listed that submitters believe will be useful for EPA's 
risk assessment. When information listed in the regulatory text is not 
submitted, a brief explanation of why such information is not available 
or not applicable should be included. Prenotice consultation may assist 
in identifying specific information appropriate for a submission.
    b. Incomplete submissions. After an initial evaluation, EPA may 
determine that a submission is incomplete and that the review period 
cannot begin (see Sec. 725.33 of the regulatory text). If EPA finds the 
submission incomplete, EPA will notify the submitter within 30 days of 
receipt of the submission and will provide the submitter with an 
opportunity to provide additional information. If the submitter 
promptly provides additional information sufficient to evaluate the 
effects of the microorganism, the evaluation will not be delayed beyond 
time for a reasonable consideration of the new information. Otherwise, 
EPA may declare the submission incomplete and the review period will 
not begin until EPA receives the necessary information.
    3. Review process. The requirements pertaining generally to the 
review process are found at proposed Secs. 725.40 through 725.60.
    a. Public involvement. EPA is aware that there is considerable 
public interest in the review of submissions involving new 
microorganisms and is committed to keeping the process as open as 
possible. Following receipt of a submission, EPA is required by TSCA to 
issue a notice in the Federal Register describing the submission (see 
Sec. 725.40 of the regulatory text). The Federal Register notice would 
include nonconfidential information on such items as the identity of 
the microorganism, the type of use, occupational exposure, production 
volume, a summary of test data included in the submission, and the 
submitter's identity. If microorganism identity and use are claimed 
confidential, EPA includes generic descriptions of this information in 
the Federal Register notice. Unit IV.D. of this preamble discusses 
confidentiality and generic descriptions. EPA would maintain a 
nonconfidential copy of the submission in the TSCA Nonconfidential 
Information Center for public inspection. The public will have an 
opportunity to comment on submissions received by EPA. The length of 
the comment period may be affected by the need to hold a meeting of 
experts to address a particular submission, or to consider novel 
scientific issues raised by the submission.
    b. State coordination. EPA has developed comprehensive procedures 
to coordinate reviews of submissions and to share scientific 
information to the fullest extent with appropriate State and local 
authorities. For example, under EPA's current procedures for review of 
field tests under the 1986 Policy Statement, within the first week of 
receipt of a submission, an EPA review coordinator contacts by 
telephone the appropriate regulatory agencies in the State(s) where the 
test will be conducted to inform them of the submission. If requested, 
a nonconfidential copy of the submission is mailed to the State. If a 
site visit is to be conducted, EPA staff contacts State and EPA 
regional personnel early in the review period to begin coordination of 
the site visit. Nonconfidential reports, assessments, and public 
comments added to the Public Docket are routinely made available to 
State personnel upon request. In addition, State personnel receive a 
copy of EPA's draft risk assessment, and comments and concerns raised 
by the State(s) are given careful attention in the risk assessment. At 
the conclusion of the review period, State personnel receive a copy of 
any document which addresses the conditions under which the field test 
can be performed.
    EPA is also requiring that persons who are preparing submissions 
for R&D activities provide evidence of having notified appropriate 
State authorities (see Sec. 725.255 of the regulatory text). Submission 
of copies of any correspondence with State authorities concerning the 
proposed field trial, for example, would satisfy this requirement. EPA 
also strongly encourages such submitters to inform communities located 
near potential test sites of their plans to introduce microorganisms 
into the environment.
    c. Use of experts. In performing assessments, EPA intends to 
supplement its staff expertise as necessary by using experts from other 
government agencies, academia, and other independent sources. EPA 
assessments may be reviewed by a subcommittee, composed of scientists 
with relevant expertise, of EPA's Biotechnology Science Advisory 
Committee (BSAC) at a public meeting. Certain portions of the meetings 
may be closed to discuss confidential business information (CBI). EPA 
will consider all BSAC Subcommittee recommendations in its final 
decisions. Procedures have been developed to ensure that experts 
contributing to EPA's biotechnology reviews will not have conflicts of 
interest.
    d. Changes to the review process. The review period starts on the 
date EPA determines the submission is complete and runs for a period of 
time specified for each submission type. A submitter may voluntarily 
withdraw a submission at any time, or suspend the review period for a 
specified period of time. Suspension of the review period may be 
beneficial when questions that arise during the notice review period 
require additional time to address. For good cause, EPA may extend the 
review period up to a total of the length of time specified for each 
type of submission.
    4. Recordkeeping and compliance. The requirements for 
recordkeeping, compliance, and inspections are found at Secs. 725.65, 
725.70, and 725.75, respectively. In addition to recordkeeping 
requirements generally applicable to all submissions, EPA is proposing 
recordkeeping requirements specific to each submission type. For 
certain exemptions from full reporting under section 5, the 
recordkeeping requirements are a key part of compliance with the 
exemption. Compliance and inspection requirements are the same as those 
for traditional chemicals.
    5. Petitions to exempt new microorganisms. Provisions for 
applications to request exemptions for new microorganisms from the 
requirements of all or part of part 725 are found at Sec. 725.67.

C. Reporting General Commercial Use of TSCA Microorganisms

    This Unit discusses who is subject to microbial commercial activity 
notice (MCAN) reporting, the MCAN submission and review process, and 
exemptions from MCAN reporting for general commercial use.
    1. Determining whether MCAN reporting is required. Subpart D of 
part 725 would require, with some exceptions, submission of a MCAN by 
persons who intend to manufacture or import new microorganisms, and by 
persons who intend to manufacture, import, or process microorganisms 
for a significant new use. A MCAN must be submitted 90 days before 
manufacture, import, or processing of the microorganism for commercial 
purposes. Because EPA has a separate, less burdensome, screening 
process for R&D involving microorganisms (see Unit II.D. of this 
preamble), the Agency expects that, in general, the MCAN will be 
submitted only for microorganisms for general commercial use.
    2. MCAN submission and review process--a. MCAN submission process. 
The purpose of EPA's review of MCANs would be similar to EPA's purpose 
in reviewing PMNs and SNUNs submitted for traditional chemical 
substances. The purpose of a MCAN would be to provide EPA with 
information necessary to identify and list a microorganism on the TSCA 
Inventory (if the microorganism is new) and to determine whether the 
microorganism would pose an unreasonable risk to human health or the 
environment. EPA must conduct a review that considers all the 
reasonably ascertainable information on potential human health and 
environmental effects of a microorganism. The information to be 
included in the MCAN is listed in Secs. 725.155 and 725.160 of subpart 
D. Submitters must develop a MCAN that describes the characteristics 
and construction of the new microorganism as well as describing 
conditions of manufacture and use. In addition, submitters must 
reference any published literature on the microorganism and its 
parental strains and submit available data from laboratory, greenhouse 
studies, and/or R&D field tests using the microorganism.
    b. MCAN review process. All reviews of microorganisms will follow 
established administrative steps that are the same for all chemical 
substances subject to 90-day review. For good cause, EPA may extend the 
initial review period by an additional 90 days, for a total of 180 
days. During this time the microorganism cannot be manufactured or 
processed for commercial purposes.
    c. Regulatory decision. EPA may reach one of three decisions during 
the review period based on a balancing of the risks and benefits 
presented by the microorganism: There is sufficient information to 
determine that the risks will not be unreasonable; there is sufficient 
information to determine that the risks are unreasonable; or there is 
insufficient information to make a reasoned evaluation of risk, and the 
substance may present an unreasonable risk or there may be significant 
or substantial human or environmental exposure to it.
    Unless EPA notifies the submitter to the contrary, the submitter 
may begin to manufacture and use the microorganism at the end of the 
90-day period. However, if the information available is insufficient to 
reasonably evaluate the risk and the substance may present an 
unreasonable risk, EPA may issue an order under TSCA section 5(e) to 
limit or prohibit the manufacture, processing, distribution in 
commerce, use, or disposal of the microorganism. In the past, EPA has 
found it useful to negotiate with submitters to develop consent orders, 
sparing both the submitter and EPA the legal proceedings that may be 
involved in a unilaterally issued order. Under a consent order, the 
submitter generally agrees to develop additional information or to 
accept certain restrictions in return for permission to proceed with 
its plans to manufacture or import the substance.
    In the situation where EPA decides that risks will be unreasonable, 
it may use TSCA section 5(f) to require measures to reduce risks to an 
acceptable level as a condition of manufacture and use. Alternatively, 
EPA may prohibit manufacture or use, if there are no measures available 
or practicable to sufficiently reduce the risk.
    3. Exemptions from MCAN reporting. Persons intending to manufacture 
new microorganisms for general commercial use may not have to submit a 
MCAN prior to commencing manufacture, if the microorganisms they intend 
to use qualify for exemptions from MCAN reporting. This unit discusses 
one exemption developed for traditional chemicals that will not be 
applied to microorganisms and two exemptions that are applicable to 
microorganisms.
    a. Low volume exemption. EPA has previously promulgated rules 
providing for an exemption from the notification requirements of 
section 5 of TSCA for new chemical substances produced for general 
commercial use in volumes less than 1,000 kilograms per year (see 40 
CFR 723.50). This exemption requires applicants to submit a notice to 
EPA 21 days before manufacture begins to provide the Agency an 
opportunity to review the chemical. EPA believes that this exemption is 
inappropriate for microorganisms, which have the ability to reproduce, 
disseminate, and transfer genetic material. EPA is therefore proposing 
to amend Sec. 723.50 to state that the exemption provisions of that 
section do not apply to microorganisms.
    b. Test marketing exemption. Test marketing activities usually 
involve limited sale or distribution of a substance within a 
predetermined period of time to determine its competitive value when 
its market is uncertain. EPA is required by TSCA section 5(h)(6) to 
grant or deny the test marketing exemption (TME) no later than 45 days 
after receipt of an application. Subpart F of part 725 proposes the 
requirements for obtaining a TME. These requirements are adopted 
verbatim from Sec. 720.38, the Agency regulations that currently apply 
to all chemicals substances.
    In general, EPA suggests that manufacturers who intend to test 
market new microorganisms file a MCAN rather than a request for a TME. 
However, there may be situations in which this exemption may be 
appropriate, such as for microorganisms which were previously reviewed 
by EPA at the R&D stage. EPA encourages anyone who is considering 
requesting a TME for a new microorganism to begin prenotice 
consultation as early as possible, so that EPA can determine if it 
would have sufficient information to determine that the test marketing 
activities would not present an unreasonable risk.
    c. Tiered exemption for general commercial use. Under TSCA section 
5(h)(4), EPA is proposing to exempt from MCAN requirements certain new 
microorganisms manufactured for general commercial use which it has 
determined will not present an unreasonable risk. Subpart G of part 725 
contains the conditions for this exemption, which consists of two 
tiers, each based on certain criteria discussed below. The rationale 
for this exemption appears in Unit III.C.7. of this preamble. 
Microorganisms produced under this exemption would not be listed on the 
Inventory.
    (i) Tier I. Manufacturers meeting Tier I requirements will be 
completely exempt from review by EPA. They would submit a one-time 
certification statement to EPA 30 days prior to the first use of a 
microorganism eligible for a Tier I exemption. The conditions for this 
exemption are listed at Sec. 725.424. The statement must include 
information identifying the manufacturer or importer, the location of 
the facility involved, and a statement certifying that the manufacturer 
complies with all the criteria required for the Tier I exemption. 
Information in the statement may be claimed confidential. A 
certification would be required for the first use of an eligible 
recipient microorganism at a specific facility. Subsequent uses of the 
same recipient microorganism at the same facility would not require 
additional certification, so long as the manufacturer complied with the 
other Tier I exemption conditions.
    (ii) Tier II. Manufacturers meeting the requirements at proposed 
Sec. 725.428 may submit an exemption request to EPA 45 days prior to 
use of the microorganisms, if they believe that containment conditions 
other than those listed at proposed Sec. 725.422 would still allow the 
requirements of the exemption to be met (see Sec. 725.455 of the 
regulatory text). Information included in such a submission may be 
claimed confidential. Submitters must certify in the request that they 
have complied with the requirements. EPA would approve or deny an 
exemption request within 45 days and could impose restrictions to 
ensure that the microorganisms would not present an unreasonable risk 
(see Sec. 725.470 of the regulatory text).
    (iii) Criteria for the exemption. Three conditions are placed on 
the Tier I and Tier II exemptions. The recipient microorganisms must be 
listed at proposed Sec. 725.420, the introduced genetic material must 
meet certain requirements, and performance-based criteria for 
containment and inactivation of the new microorganisms are to be used.
    (A) Recipient microorganisms. EPA is proposing that new 
microorganisms certified to be developed using a recipient species or 
strain listed at proposed Sec. 725.420 would qualify for the tiered 
exemption.
    (B) Introduced genetic material. The introduced genetic material 
used to modify the recipient microorganisms must be well characterized, 
limited in size to the genetic material required to perform the 
intended function, and poorly mobilizable (see Sec. 725.421 of the 
regulatory text). Further explanation of these terms appears in Unit 
III.C.7. of this preamble. In addition, genetic material which encodes 
for all or part of the toxins listed in proposed Sec. 725.421(d) may 
not be used to modify any recipient microorganism.
    (C) Containment and inactivation. EPA is also proposing 
performance-based criteria for limiting exposures. These criteria would 
have to be used for the Tier I exemption, because EPA would not review 
these activities prior to production. For the Tier II exemption, 
because the containment and inactivation controls would be reviewed in 
the exemption request, the criteria would serve as guidance for 
submitters. Proposed Sec. 725.422 lists the criteria for containment 
and inactivation at a facility.
    (iv) Exemption applications. Using the provisions in proposed 
Sec. 725.67, individuals may submit an application under section 
5(h)(4) requesting that a recipient microorganism be added to the 
exempt list. Submitters may request an exemption with different 
conditions. EPA would evaluate the request using appropriate procedures 
under section 5(h)(4).

D. Reporting R&D Activities for TSCA Microorganisms

    This Unit discusses EPA's proposal for which microorganisms are 
subject to R&D reporting and recordkeeping, exemptions from R&D 
reporting, and the TSCA experimental release application (TERA) 
submission and review process.
    1. Overview of considerations for determining whether a researcher 
has TSCA section 5 obligations for R&D activities. Persons planning to 
conduct R&D activities involving new microorganisms subject to TSCA may 
be subject to these rules. While any researcher may submit a complete 
MCAN as required for general commercial use, EPA is proposing a number 
of exemptions from MCAN reporting that reduce researchers' reporting 
obligations under TSCA section 5. All R&D activities are eligible for 
reporting using the TERA process which is discussed below. However, EPA 
expects that the TERA will be used primarily for environmental 
experiments. Laboratory and other research in contained structures 
would more likely comply with certain recordkeeping requirements 
provided under TSCA section 5(h)(3) in the rule. Finally, certain 
research may be exempt from TSCA section 5, because EPA has determined 
review is unnecessary altogether or it is appropriate to defer in 
whole, or in part, to another Federal agency.
    The series of considerations to be used to determine TSCA section 5 
obligations for R&D activities is displayed in chart form in Figure 1 
below. The following paragraphs summarize the steps on Figure 1.
    The first three steps list the issues that must be addressed for 
determining if any substance is subject to TSCA section 5 reporting, 
whether for general commercial use or for R&D activities. The 
subsequent steps are employed to determine R&D obligations. Determining 
whether an R&D activity is subject to TSCA jurisdiction and whether the 
microorganism is intended for commercial purposes are discussed below 
in Units II.D.2.a. and 2.b., respectively. Determining whether a 
microorganism is ``new'' for the purposes of TSCA section 5 is 
discussed in Unit I.C. of this preamble.
    If researchers have determined that their R&D activities are 
subject to TSCA jurisdiction, are intended for commercial purposes, and 
involve new microorganisms, their R&D activities will be subject to 
some obligations under TSCA section 5. Researchers would then proceed 
through the remainder of the questions to determine their reporting 
status. They would first determine whether their R&D activities are 
eligible for the contained structures exemption. This determination is 
discussed below in Unit II.D.2.c.
    The next question deals with other agencies. An R&D activity that 
is eligible for the contained structures exemption may also be subject 
to the authority of another Federal agency. Overlapping jurisdiction 
for R&D conducted in contained structures is discussed below in Unit 
II.D.2.d.
    If the R&D activity does not qualify for the contained structures 
exemption, TERA reporting would next need to be considered. However, 
EPA is also proposing in this rulemaking a category of specific 
microorganisms that are exempt from TERA reporting. Thus, researchers 
who are not eligible for the contained structures exemption and/or for 
deferral to another agency may qualify for a specific TERA exemption. 
The determination of whether the research qualifies for a TERA 
exemption is discussed below in Unit II.D.2.e.
    Figure 1 shows the four distinct types of TSCA section 5 
obligations existing for R&D activities. The reporting requirements for 
each of these obligations are discussed below in Units II.D.3. and 4. 
The corresponding paragraphs are noted on the following Figure 1.

TP01SE94.000

    2. Specifics for determining eligibility for R&D exemptions. The 
five points which researchers must consider in order to determine their 
TSCA section 5 obligations for R&D are discussed in this paragraph.
    a. Determination that the R&D activity is subject to TSCA 
jurisdiction. Statutory jurisdiction is discussed in Unit I.C. of this 
preamble. As noted in that Unit, uses of some microorganisms are 
specifically excluded from TSCA section 5, because they are subject to 
other statutes. Uses that are not specifically excluded are subject to 
TSCA. When developing the initial TSCA Inventory, EPA indicated that 
undifferentiated uses of chemical substances would be subject to TSCA 
(42 FR 64585, December 23, 1977). In the 1986 Policy Statement, EPA 
stated that unless the uses were explicitly excluded by TSCA, ``all 
microorganisms produced for environmental, industrial, or consumer uses 
are potentially regulable under TSCA'' (51 FR 23324, June 26, 1986). 
Thus, EPA would consider that R&D activities involving new 
microorganisms where researchers are unsure of the final use would be 
subject to TSCA section 5. This would include microorganisms in early 
stages of research, where the researchers have not determined a 
specific commercial application of the microorganism. As noted in Unit 
II.B. of this preamble, researchers who are uncertain of the status of 
their microorganism, for any reason, should consult EPA regarding their 
TSCA section 5 obligations.
    b. Determination that the R&D activity is intended for commercial 
purposes. TSCA section 5 covers only uses of new microorganisms for 
commercial purposes. EPA discusses its interpretation of commercial R&D 
in Unit III.A. of this preamble. The Agency is proposing three 
alternative interpretations of commercial purposes. Depending on public 
reaction to the alternative interpretations discussed in this proposal, 
the interpretation of commercial R&D could differ from one R&D activity 
to another in a final rule, if public comment supports different 
interpretations for different types of R&D activities.
    c. Determination that the R&D activity is eligible for the 
contained structures exemption. This exemption would most likely apply 
to research performed in contained structures such as pilot 
fermentation plants, greenhouses, laboratories, and certain bioreactors 
used for waste treatment. The term ``structure'' is defined in proposed 
Sec. 725.3. Research involving intentional testing of microorganisms in 
the environment would not be eligible for this exemption. Requirements 
for the exemption are in section 3 of this Unit. The rationale for this 
exemption is discussed in Unit III.B. of this preamble.
    d. Determination that oversight of the R&D activity is also subject 
to the authority of another Federal agency. Some R&D activities may be 
subject to the authority of another Federal agency in addition to EPA. 
Where there is overlapping jurisdiction for R&D activities that are 
eligible for the contained structures exemption, EPA proposes to defer 
to the other Federal agency which has authority for oversight over such 
activities. This would apply to researchers who are receiving funding 
from the other Federal agency, which requires that researchers comply 
with the ``NIH Guidelines for Research Involving Recombinant DNA 
Molecules'' (``NIH Guidelines'') in order to receive funding. 
Researchers who are voluntarily complying with the NIH Guidelines but 
are not actually receiving funding from a Federal agency would not be 
eligible for the deferral.
    e. Determination that specific microorganisms are exempt from TERA 
reporting. EPA is proposing exemptions from TERA reporting for certain 
new microorganisms derived from the microorganisms Bradyrhizobium 
japonicum and Rhizobium meliloti. R&D involving these microorganisms 
performed in accordance with specified conditions would be exempt from 
review. Additional microorganisms may be exempted by rule under section 
5(h)(4), as EPA gains familiarity with them. Unit III.C.5. of this 
preamble discusses the rationale for this exemption.
    3. Requirements necessary for eligibility for exemptions from TERA 
reporting. Once researchers have determined which exemptions their R&D 
activities are eligible for, they must determine their specific TSCA 
section 5 obligations. Proposed Secs. 725.232 through 725.239 specify 
the requirements for each of the exemptions from TERA reporting.
    a. The contained structures exemption--(i) R&D subject to another 
Federal agency. R&D activities which are eligible for the contained 
structures exemption (see Sec. 725.234(a) and (c) of the regulatory 
text) but are also subject to the oversight of another Federal agency 
will be exempt from the requirements of TSCA section 5. If researchers 
comply with the other agency's requirements, there will be no EPA-
specific requirements (see Sec. 725.232 of the regulatory text).
    (ii) R&D not subject to another Federal agency. This document 
proposes that R&D eligible for the contained structures exemption but 
not subject to another Federal agency must be conducted in accordance 
with proposed Secs. 725.234 (containment and recordkeeping) and 725.235 
(employee notification). Although researchers that comply with these 
provisions are not required to report to EPA under TSCA section 5, the 
recordkeeping and employee notification requirements would apply and 
would be enforceable by EPA.
    There are two types of standards in Secs. 725.234 and 725.235. The 
employee notification standards of Sec. 725.235 are taken directly from 
current regulations in Secs. 720.36 and 721.47, and are the same as 
those for traditional chemical substances. Section 725.234 contains 
general research standards but adds some provisions that apply 
specifically to microorganisms. However, these additional provisions 
are minor changes to EPA's current requirements for the research 
exemption, and these provisions should be standard practices for 
research activities involving microorganisms.
    Specifically, the small quantities exemption for traditional 
chemical substances requires research to be conducted by, or directly 
under the supervision of, a technically qualified individual (TQI). 
This is a requirement under EPA's current regulations at Secs. 720.36 
and 721.47. Section 725.234 applies the same requirement to 
microorganisms eligible for the contained structures exemption.
    Section 725.234 states that the TQI must select appropriate 
measures to control release of the research microorganism, write a 
brief description of the reasons for choosing the measures and ensure 
maintenance of records to document routine use of the selected 
controls. In addition, the choice of control measures must be certified 
by an authorized official of the institution at which the research is 
conducted. Finally, EPA may request that the records be sent to EPA for 
review. Subsequent to such review, EPA may in some circumstances offer 
recommendations to modify control or documentation measures. In what 
EPA anticipates would be rare occurrences, EPA might order the 
researcher to modify controls or documentation measures. Failure to 
comply with such an order would result in loss of eligibility for the 
exemption for the specific R&D activity.
    For those researchers who are voluntarily complying with, but are 
not subject to, the NIH Guidelines, the requirements of the contained 
structures exemption could be met by having the principal investigators 
serve as the TQIs (see Sec. 725.234(b) of the regulatory text) and keep 
records indicating that they abide by the NIH Guidelines.
    b. Exemption from TERA reporting for specific microorganisms. In 
order to be exempt from both TERA reporting and MCAN reporting, persons 
using the exemptions for microorganisms listed in Sec. 725.239 must 
comply with the general requirements for the exemption listed in 
Sec. 725.238 as well as any specific requirements listed in 
Sec. 725.239. Similar to its proposal for the tiered exemption for 
general commercial use discussed in Unit II.C., EPA is proposing to 
place restrictions on the recipient microorganisms, the introduced 
genetic material, and the conditions of use (see Sec. 725.239 of the 
regulatory text).
    4. TERA submission and review process. EPA is proposing to 
establish the TERA, which is an abbreviated notification process for 
environmental testing of new microorganisms.
    a. TERA submission process. Sections 725.255 and 725.260 detail 
specific information that should be submitted with a TERA. The basic 
microorganism identity information is the same as that for the MCAN. 
Other information requested specifically addresses the proposed R&D 
activity and therefore is not as extensive as the MCAN information.
    b. TERA review process. EPA's goal is to review TERAs in 60 days 
(see Sec. 725.270 of the regulatory text). For good cause, EPA could 
extend the initial TERA review period by an additional 60 days, for a 
total of 120 days (see Sec. 725.56 of the regulatory text). Due to the 
small number of experiments that have been conducted and the 
uncertainty concerning field tests that involve new microorganisms, EPA 
expects that initial TERA reviews may take closer to 120 days. During 
the prenotice consultation, EPA would estimate for the submitter 
whether the review is likely to require closer to 120 days or 60 days.
    Generally, EPA believes that approval of TERAs in 60 days or less 
would be possible for field tests that are similar to previously 
reviewed field tests (for example, use of the same or similar 
microorganisms, modifications to a previous test, or change in 
geographic conditions). When novel circumstances are presented in a 
TERA, however, EPA may need to extend the review period in order to 
complete its review. Specific examples of extension for good cause 
would include the need for a subcommittee meeting of the Biotechnology 
Science Advisory Committee to supplement Agency expertise or the need 
to coordinate review with other Federal agencies. When EPA coordinates 
the review of a microorganism with another Federal agency, the review 
period would automatically be extended to the length of the other 
agency's review, to allow the two agencies to coordinate reviews and 
decisionmaking. TERA submitters may not proceed with their field trials 
until EPA has provided written approval of the TERA submission. As soon 
as EPA completes its review, however, researchers will be able to start 
their test immediately upon notification from EPA.
    c. Regulatory decision. EPA will approve a TERA if it determines 
that the experiment(s) will not present an unreasonable risk to human 
health or the environment. If the submission is approved, EPA may 
negotiate with the submitter a TERA Agreement, which would be legally 
binding on all parties and would set out any conditions governing the 
conduct of the specific field trial (see Sec. 725.270 of the regulatory 
text). The TERA Agreement could include provisions for maintaining 
restrictions on the use of the test site after the completion of the 
test. This may require the submitter to make appropriate arrangements 
with the owner of the test site, in cases where the submitter does not 
own the test site. If EPA concludes that the proposed R&D activity may 
present an unreasonable risk of injury to human health or the 
environment, EPA will deny the TERA and will provide reasons for the 
denial in writing. Section 725.288 provides for revocation or 
modification of TERA approvals following the receipt of additional 
information.
    5. Options for oversight of R&D activities--a. Range of options 
possible. EPA's intent in offering a variety of alternatives for 
oversight of R&D activities was to provide a flexible process which 
tailored oversight to the level of risk. In developing TSCA section 5 
obligations for R&D activities using new microorganisms, EPA looked at 
a range of options. These fall on a continuum ranging from an option 
which would exempt all R&D activities under a small quantities 
exemption similar to the exemption for traditional chemicals to an 
option which would require TERA reporting for all R&D activities, 
including those conducted in laboratories and other contained 
structures.
    As discussed in Unit III.B. of this preamble, because 
microorganisms can multiply and spread beyond the site of introduction, 
EPA must redefine the small quantities definition applied to 
traditional chemicals. EPA developed the TERA process, because it 
believes that review of environmental uses of microorganisms should 
begin during the R&D stage. At the same time, EPA does not believe that 
all microorganisms used in all R&D activities should be subject to TERA 
reporting. Neither of the extreme options seemed appropriate to EPA for 
coverage of R&D, because they would not be tailored to potential risk. 
Thus, EPA chose an intermediate approach.
    In keeping with the goals of the Coordinated Framework, EPA has 
included in its proposed option opportunities to address overlapping 
jurisdiction with other Federal agencies. EPA has attempted to balance 
the Coordinated Framework's goal to reduce duplicative oversight with 
TSCA section 5's goal to screen for potential unreasonable risks. As 
discussed in Unit III.B. of this preamble, in developing its 
requirements for the contained structures exemption, EPA selected an 
approach which recognized the diversity of microorganisms which would 
be used in research and therefore left to the researcher the choice of 
appropriate containment and inactivation controls. Additionally, in 
order to keep the TERA process flexible, EPA has developed a provision 
allowing microorganisms tested in the environment to be exempted from 
TERA reporting as the Agency gains more familiarity with them.
    EPA requests comments on its proposed option for R&D activities for 
TSCA microorganisms. In particular, EPA would like to know whether 
commenters feel that the flexibility provided by the various exemptions 
available under the proposed option counterbalances the complexity of 
the approach. The public may suggest other options along the continuum, 
providing those options also meet the intent of TSCA and adequately 
protect public health and the environment from unreasonable risks. In 
addition to the proposed option, when EPA prepares its final rule, it 
will consider the variety of options along the continuum discussed 
above, as well as options suggested by the public.
    b. Specific alternative for low risk field tests. EPA realizes that 
there are a variety of possible options along the continuum discussed 
above. Although EPA has decided that case-by-case review is important 
for many microorganisms intentionally tested in the environment, EPA 
recognizes that there will be low risk field tests that would not 
require TERA review. For this reason, some have suggested an 
alternative exemption for certain R&D releases. This alternative, which 
is similar to the R&D contained structures exemption in that it would 
be dependent on determinations made by a TQI, would apply to certain 
low risk field tests and would be included with the exemptions which 
are part of the proposal for coverage of R&D activities under TSCA 
section 5. Like the proposed exemption for R&D in contained structures, 
this alternative would contain requirements for documentation and 
recordkeeping by a TQI and certification by an authorized company 
official. It would also provide for EPA to inspect records and order 
changes, if necessary.
    Under this alternative, a company planning a small-scale field test 
which meets the eligibility requirements for the exemption would have 
the option of submitting a TERA for review by EPA or submitting a 
notice with the determination that the field test qualified for the 
exemption. The alternative includes a number of requirements which are 
intended to minimize the likelihood of inconsistent determinations.
    The TQI would be expected to make the determination that the new 
microorganism was eligible for the exemption, based on the following: 
(1) The test site must be 10 acres or less of land, (2) the parent 
microorganism(s) must have a history of safe use, and (3) the 
introduced genetic material must be limited in size, well-
characterized, free of certain nucleotide sequences, and poorly 
mobilizable. Further explanation of the terms in (3) appears in Unit 
III.C.7. of this preamble.
    In determining that the parent microorganism has a history of safe 
use, EPA would expect researchers to be able to classify taxonomically 
the microorganism and to evaluate its relationship with closely related 
microorganisms which may have a potential for adverse effects on human 
health or the environment. Information on the potential for the 
microorganism to cause adverse effects on human health and the 
environment should be evaluated.
    EPA recognizes that a determination that a microorganism has a 
history of safe use involves a balancing of various factors. This 
determination should be premised on the researcher's prediction of the 
behavior of the microorganism based on experience with its use. The 
more information the researcher has on the behavior of the 
microorganism (for example, the ability to establish, compete, and 
survive in the environment), the better the researcher can estimate the 
safety of the field test. In conducting their risk assessment, 
researchers should consider the scale, since the tests must be 
conducted on 10 acres or less of land.
    An additional requirement for this alternative exemption would be 
that an official having authority to represent the organization (e.g., 
the Chief Executive Officer, the General Counsel) certifies that the 
determination has been made by a TQI and is considered to be the 
official position of the organization. The official would also be 
required to state that the organization accepts full liability for all 
potentially harmful consequences of the field test. To show that 
relevant considerations had been evaluated, a TQI would be required to 
prepare a written analysis to be kept in the company's records. These 
records would be kept for 5 years from the date of the field test, with 
EPA retaining the right to review the records upon request. In lieu of 
a TQI, the analysis could be performed by a third party review group 
with relevant scientific expertise (i.e., ecological expertise) as 
exemplified by the Institutional Biosafety Committees (IBCs) described 
in the NIH Guidelines.
    Following the TQI's determination, the researcher would be required 
to submit a short notice to EPA, providing the organization name and 
address, a summary of the new microorganism and the proposed field 
test, the name of the TQI, and the official certification, including 
the liability statement. EPA would have 45 days to determine whether to 
require submission of a TERA before the researcher could conduct the 
planned field test.
    EPA requests comments on this alternative approach for low risk 
field tests. In particular, EPA would like to know whether there are 
other criteria which would be appropriate for defining a category of 
low risk small-scale field tests and what additional guidance would be 
needed for researchers to utilize such an approach. The rationale for 
this alternative exemption is discussed in Unit III.C. of this 
preamble.

III. Rationale for Proposed Reporting Mechanisms

A. Research for Commercial Purposes

    1. Introduction. TSCA section 5(i), while it limits all section 5 
screening to activities for commercial purposes, has had little 
practical effect on research using traditional chemicals, because of 
the research exemption. However, because this proposed rule would place 
more requirements on research with microorganisms than on research with 
traditional chemicals, EPA believes it should provide its current view 
on the applicability of the commercial purposes limitation to this 
proposed rule.
    As a preliminary matter, there is no difficulty in determining when 
any chemical substance, including a microorganism, is being 
manufactured or processed for a commercial purpose after the R&D stage. 
It is clear when a PMN is required or when a MCAN would be required at 
general commercial use.
    Research on traditional chemicals is not generally affected by the 
commercial purposes limitation, because EPA's current regulatory 
definition of small quantities for R&D using traditional chemicals (any 
amounts reasonably necessary for research) at Sec. 720.3 effectively 
exempts research with these chemicals from section 5 screening. 
However, as noted in Unit III.B. of this preamble, these rules propose 
a small quantities definition for microorganisms; and this definition, 
because it would recognize the ability of microorganisms to reproduce, 
would differ from the definition for traditional chemicals. A 
researcher utilizing microorganisms, therefore, may need to consider 
what constitutes a commercial purpose.
    Research involving microorganisms used in contained structures 
would be considered ``small quantities solely for research and 
development'' as defined at Sec. 725.3 of the regulatory text. Although 
EPA expects the requirements for this contained structures exemption 
simply to reflect common practices, a researcher may have to evaluate 
whether research conducted in contained structures is commercial. The 
contained structures exemption would not apply to field testing of 
microorganisms because of the ability of living microorganisms to 
reproduce and spread in the environment (see Unit III.B. of this 
preamble). As a result researchers will, in all cases, need to decide 
which environmental testing is commercial.
    EPA wishes to emphasize that any coverage of research under this 
proposed rule should not duplicate appropriate oversight by other 
Federal authorities. As explained in Unit III.C.3. of this preamble, 
contained research appropriately overseen by other Federal agencies 
would be exempt from EPA oversight, because EPA believes such research 
does not present an unreasonable risk. As a practical matter, 
therefore, while testing conducted at institutions that do not normally 
consider themselves commercial (academic and non-profit institutions) 
could theoretically be commercial under interpretations discussed in 
this Unit, EPA anticipates that other parts of these rules will exempt 
much of the research from EPA oversight.
    2. Public comments. During development of regulations on 
biotechnology, EPA has received numerous public comments that differ 
substantially on oversight of research. Of particular concern has been 
the appropriateness of EPA review based on the status of an activity as 
commercial rather than on its potential risk.
    Comments argue that there is no reason to suspect any difference in 
risk between commercial or noncommercial research. Thus, if a 
university and a business release the same microorganism in similar 
settings, both should be subject to oversight.
    On the other hand, comments suggest there may be risk differences. 
Some argue that a commercial enterprise is more likely to be careful 
than a noncommercial institution due to concern for liability. Others 
argue that academic researchers are more likely to be concerned with, 
and aware of, the need to consider health and environmental safety 
issues and that commercial entities may be willing to take shortcuts in 
the interest of reducing costs.
    Other comments complain that increased government regulations may 
have a deleterious effect on academic research, because it may be more 
difficult for pure research institutions to comply. Burdens that are 
relatively minor for a business could be major for a university or an 
individual researcher.
    Comments have also indicated that a number of practical 
difficulties increase the burden on research institutions. For example, 
increasingly complex and intermingled financial arrangements in the 
biotechnology field have emerged as universities seek funding from 
businesses. These arrangements may result in universities conducting 
product development for money or equipment donations from business. 
Undue burdens to academic researchers can result from requirements that 
research which is funded by a commercial entity be distinguished from 
that funded by a noncommercial entity, particularly when a university 
may pool its funds from various sources.
    Finally, even though an academic research institution may engage in 
product development for a business, the institution may not be engaging 
in a commercial activity for its own benefit. For example, a university 
may use income from a commercial entity to improve its teaching and its 
ability to increase knowledge. Industry could be an important source of 
income for upgrading equipment used for teaching.
    The remainder of this Unit discusses EPA's view of the law and 
policy and responds to these public comments.
    3. EPA's view of the law as it applies to commercial activities at 
noncommercial institutions. EPA wishes to make it clear that the 
interpretations discussed in this Unit are consistent with 
interpretations in current regulations. That is, a commercial activity 
is one undertaken with the purpose of obtaining an immediate or 
eventual commercial advantage. This is the common thread in 
Sec. 720.3(r) which defines ``manufacture or import for commercial 
purposes'' and Sec. 721.3 which defines ``process for commercial 
purposes.'' Similarly, Sec. 720.30(i) provides that ``non-commercial 
research and development'' consists of activities conducted by 
academic, government, or independent not-for-profit organizations 
``unless the activity is for eventual commercial purposes.''
    All research conducted directly by a commercial entity is clearly 
for commercial purposes, as was decided in The Dow Chemical Company v. 
EPA, 605 F.2d 673 (3d Cir. 1979). Consequently, if a business directly 
funds a research activity for product development, the activity is for 
commercial purposes, regardless of the location. A business may not 
avoid review by simply funding research at an academic institution.
    In section 5, Congress distinguished between commercial and 
noncommercial activities and, thus, expected them to be treated 
differently. Although the statute has no definitive explanation as to 
what this distinction means, it does not appear to have been risk-
based. EPA believes that Congress did not provide a definitive 
explanation and therefore left to the Agency's discretion the balancing 
of competing interests. TSCA section 2(b) states that it is the policy 
of the United States that TSCA authority should be exercised so as not 
to ``impede unduly or create unnecessary economic barriers to 
technological innovation,'' while fulfilling the primary purpose of 
assuring that innovation does not present unreasonable risks.
    If EPA considers that section 5 provides a screening mechanism, as 
opposed to a direct regulatory mechanism, EPA has an indication why the 
commercial purposes limitation applies. Under other TSCA provisions, 
EPA may regulate without regard to a commercial purposes limitation. 
For example, the commercial purposes limitation does not apply to EPA's 
authority under TSCA section 6 to prohibit or limit manufacture, 
processing, or distribution in commerce of chemical substances if the 
Agency finds that the particular activities present an unreasonable 
risk.
    By providing a commercial purposes limitation for EPA to cover 
early phases of product development, Congress recognized the need for 
EPA to balance the competing interests of fostering innovation and 
protecting human health and the environment from unreasonable risk. In 
balancing these interests, EPA could construe the commercial purposes 
limitation to exclude relatively few activities during screening to 
cover a broad range of risk possibilities. Therefore, the broadest 
meaning of commercial purposes would miss hardly any research.
    4. Alternative interpretations affecting which activities at 
noncommercial institutions will be considered commercial. Any of the 
three alternative interpretations of commercial purposes set forth 
below, as well as any other interpretation that is suggested by public 
comment and meets the intent of TSCA and adequately protects public 
health and the environment from unreasonable risks, may be adopted by 
the Agency in its final rule. Regardless of the alternative chosen, EPA 
would encourage researchers to voluntarily consult with EPA to find out 
if EPA considers their research to be commercial.
    a. Indicia of commercial purposes. The usual way to interpret a 
statutory term of art like ``commercial purposes'' would be to look for 
indicia of commercial intent. This is what EPA does in its TSCA section 
5 program for traditional chemicals. The Agency has not provided any 
detailed public discussion of what these indicia may be for traditional 
chemicals, but because the Agency will be reviewing R&D activities in 
its biotechnology program, a discussion of these indicia for the 
biotechnology program is appropriate.
    While EPA may develop a general discussion, no exhaustive list of 
commercial indicia can be developed a priori. If EPA adopts this 
approach, the commercial indicia would apply to R&D in laboratories and 
other contained structures, as well as to intentional testing in the 
environment. Some environmental testing of new microorganisms would not 
be screened, because it would not be for commercial purposes.
    EPA acknowledges that noncommercial institutions may find it 
difficult to trace funding for particular activities or to decide 
whether an activity is commercial or not. However, EPA supports this 
alternative, under the theory that the burdens of reporting to EPA are 
costs of doing business for any organization that wants the benefits of 
commercial financing. In addition, EPA believes that reporting at the 
research stage under this proposed rule does not impose an unnecessary 
burden on innovation and that the indicia described below would be 
consistent with the intent of TSCA. There are two general categories of 
commercial indicia for activities at nonprofit institutions; one 
involves industry involvement, either directly or indirectly; the other 
does not.
    (i) Direct industry involvement. As noted above, any direct 
industry involvement in an activity at a noncommercial institution is 
for commercial purposes. Examples of direct commercial funding include 
situations in which a commercial entity contracts directly with a 
university, or gives a conditional grant where the commercial entity 
holds patent rights, or establishes a joint venture where the 
commercial entity holds patent or licensing rights.
    (ii) Indirect industry involvement. Indirect benefits to the 
commercial entity are not as clear. For example, a commercial entity 
may give a gift to a research institution with no limits on the use of 
the funds or research results. However, since the funds originated from 
a commercial source, a commercial purpose may nonetheless exist. Other 
indirect relationships between commercial and noncommercial entities 
need to be considered. For example, a commercial entity may guarantee a 
university bank loan for research, a faculty member associated with 
biotechnology research may have a financial interest in a biotechnology 
company, research may be conducted at a science park jointly owned by a 
university and commercial enterprises.
    (iii) No industry involvement. If there is no industry involvement, 
EPA needs to look at the intent of the individual researcher or 
institution. Entrepreneurial faculty members may obtain financial 
rewards from their own inventions. Some may take out personal patents 
or derive personal income. The university may benefit from the patents 
or may sell products or services commercially, for example, to farmers. 
Because products may be sold to consumers, EPA is inclined to consider 
these activities commercial. However, if profits are used to support 
research or improve teaching facilities, EPA may recognize a case for 
considering the activity not to be commercial.
    EPA could also consider activities supported by Federal or State 
government to be commercial. Many of these government activities are 
designed to foster economic benefits for particular groups, such as 
farmers. Also, the government may support university centers for 
technology transfer to industry. The issue may be philosophical, 
regarding whether government economic activities benefit individuals or 
the general welfare. EPA believes there are legitimate arguments for 
either view.
    Finally, EPA may consider all activities at a nonprofit institution 
to be commercial if any activity is. Thus, if a company finances one 
activity at the university, all of the university's research may be 
considered commercial. If a university has an equity interest in a 
biotechnology company or a faculty member is associated with a firm, 
all the university's research activities may be considered commercial. 
This interpretation is supported by the fact that commercial activities 
free resources for noncommercial activities.
    If EPA interprets all these situations strictly, for practical 
purposes, almost all research could be commercial. EPA notes for 
comment, however, not-for-profit institutions that obtain self-
generated funds through charitable or religious donations and 
government grants for pure research to identify health or environmental 
hazards. These situations may not be commercial under any 
circumstances.
    Regardless of the alternative chosen for environmental research, 
EPA would base its interpretation of commercial purposes for research 
qualifying for the contained structures exemption on the broad set of 
indicia discussed under this first alternative, in light of its belief 
that EPA requirements for contained commercial R&D are similar to 
requirements placed on academic researchers by the NIH Guidelines. See 
Unit III.B. of this preamble. Therefore, the second and third 
alternatives would apply only to research which does not qualify for 
the contained structures exemption.
    b. All environmental research is commercial. Because of the ability 
of microorganisms to reproduce, disseminate and spread and the features 
of intentional testing in the environment, EPA believes it should 
propose another interpretation to address such testing. Under this 
interpretation, all intentional testing outside of contained structures 
would be commercial. This interpretation would avoid the most 
significant problem identified by comments, which is that there is no 
real difference in risk between research conducted by industry and by 
noncommercial entities.
    As discussed more fully in Unit III.B. of this preamble, 
microorganisms function differently than other chemical substances. 
Because R&D involving the introduction of new microorganisms into the 
environment involves greater uncertainty than R&D involving use of 
microorganisms under contained conditions, EPA believes that a 
different position is warranted for intentional testing of 
microorganisms in the environment.
    Because the TERA burden is structured to be minimal, EPA believes 
reporting will not seriously restrict academic R&D. In fact, this 
interpretation of commercial purposes in some respects could lessen the 
burden on universities, because they will not have to separate their 
industry funding from other funding that they may not consider 
commercial.
    While considering all environmental releases to be commercial may 
seem contrary to the usual view, the actual status of funding for the 
biotechnology industry supports this interpretation. Research 
relationships in biotechnology are pervasive and take many forms. 
According to an Office of Technology Assessment (OTA) report,

    in recent years, the rapid proliferation of collaborations in 
biological research, involving partnerships between universities, 
industry and government, has greatly extended the frequency, scope 
and visibility of such activities. Attempts to commercialize 
biological techniques have occurred at an accelerated rate when 
compared to other fields, involving a greater range of commercial 
application than discoveries in most other disciplines. (Ref. 4, 
page 13).

    Even the United States government is involved, under the Technology 
Transfer Act, in the commercialization of biotechnology, having 
developed a technology transfer policy between universities and 
industry with the goal of developing commercially useful products. 
Nonprofit foundations also participate in activities for commercial 
purposes, often to finance other nonprofit activities.
    c. Rebuttable presumption of commercial activity. The same 
arguments for the option that all environmental releases are commercial 
support the rebuttable presumption option. The rebuttable presumption 
is also supported by the need to distinguish commercial and 
noncommercial activities under TSCA. The above discussion of commercial 
indicia indicates the types of evidence that a researcher may present 
to rebut the presumption. However, EPA believes that this option would 
be burdensome to researchers, because it would require them to maintain 
evidence concerning sources of funding for each environmental 
experiment. EPA also believes that this approach would be less 
protective of public health and the environment, because it does not 
adequately address uncertainty about the behavior of new microorganisms 
in the environment.
    d. Voluntary consultation. EPA recognizes that regardless of the 
interpretation of commercial purposes adopted for the final rule, it 
will be difficult to apply any one interpretation in all cases. For 
this reason, EPA would encourage persons who believe that they are 
engaging in non-commercial R&D to voluntarily consult the Agency before 
initiating testing of microorganisms that would be considered new if 
used for commercial purposes.

B. Exemption for Research in Contained Structures

    This Unit explains EPA's reasons for exempting from section 5 
screening R&D activities performed under conditions that would minimize 
the number of microorganisms emitted, or where appropriate prevent 
emission of microorganisms from structures such as pilot fermentation 
facilities, greenhouses, and laboratories. The R&D reporting process is 
discussed in Unit II.D. of this preamble.
    1. Background. The statutory authority for this exemption is TSCA 
section 5(h)(3). Section 5(h)(3) exempts from section 5 screening 
chemical substances manufactured or processed in small quantities 
solely for R&D, and directs EPA to define small quantities by rule. 
Accordingly, proposed Sec. 725.3 provides that R&D activities involving 
microorganisms would qualify for the section 5(h)(3) exemption when 
these activities are conducted under conditions designed to meet 
appropriate standards of containment and when employees are notified of 
risks. Some R&D activities which are eligible for the contained 
structures exemption may also be subject to the jurisdiction of another 
Federal agency. In these cases, EPA proposes to defer to the authority 
of the other Agency. The rationale for this proposed deferral is 
discussed in Unit III.C.3. of this preamble.
    2. Difficulties in ensuring that microorganisms used for R&D will 
not increase beyond small quantities. EPA's current regulations for 
traditional chemicals at Sec. 720.3(cc) define ``small quantities 
solely for R&D'' as those quantities that are ``not greater than 
reasonably necessary for ... [R&D] purposes.'' This definition of small 
quantities for R&D has been appropriate for traditional chemical 
substances, because these chemicals do not have the ability to increase 
their own volume or amount. To the extent a finite amount of a 
traditional chemical released during an experiment may leave a test 
site, it will only be diluted in the environment.
    Living microorganisms are not, however, subject to these same 
limitations. Microorganisms may reproduce and increase beyond the 
number initially introduced, may establish in the environment (i.e., 
develop a self-sustaining population), and may spread beyond the test 
site. Thus, what begins as a small, localized population of 
microorganisms may become a large, widespread population. Even if 
certain microorganisms do not exhibit the ability to reproduce, 
increase in number, establish, and spread beyond the test site, they 
may be capable of passing some of their traits to other microorganisms 
in the environment. These other microorganisms may, in turn, multiply, 
establish, spread and subsequently pass the acquired trait to other 
microorganisms. This could result in widespread propagation of the 
trait, and exposure of a number of different environments to novel 
traits.
    These abilities of living microorganisms render the general 
definition of small quantities that applies well to traditional 
chemicals invalid for microorganisms. If the definition developed for 
traditional chemicals was applied to living microorganisms, EPA would 
not review microorganisms until they were produced for general 
commercial use. New microorganisms could be released, with no EPA 
review, during R&D testing in the environment, perhaps numerous times, 
and could become established and spread. This would defeat the purpose 
of TSCA, which is designed to permit EPA to review chemical substances 
before they become widely disseminated.
    Consequently, a determination of what constitutes small quantities 
for microorganisms requires that more factors be taken into 
consideration than are considered for traditional chemicals. These 
factors revolve around the probability that a microorganism will 
establish itself in the environment. Establishment is a key 
consideration, because unless a microorganism establishes, any effects 
it might have would probably be spatially and temporally limited. 
Several factors influence whether a microorganism will be able to 
establish itself. These include the numbers of microorganisms involved, 
the frequency with which they are applied to the area, the method of 
application, the characteristics of the microorganism, the 
physiological condition of the microorganism at the time of 
application, and the characteristics and condition of the receiving 
environment.
    Case histories of both disease epidemics and invasions of higher 
organisms suggest that the number of organisms present in the inoculum 
directly influences whether the introduction yields a self-sustaining 
population (Ref. 5). Experience with microorganisms used in biocontrol 
(i.e., purposeful use of microorganisms as antagonists to reduce the 
disease-producing ability of plant pathogens) has shown that success in 
some instances can be enhanced if a large number of the biocontrol 
microorganism is introduced (Ref. 6).
    It can be inferred from this information that the number of 
organisms, both with regard to the density of the inoculum and the 
geographic range over which it is introduced (Refs. 7 and 8), is 
related to probability of establishment. Several hypotheses on why this 
may be so can be offered. In some cases, mortality in the introduced 
population can be overcome if the inoculum contains a large number of 
individuals. In other situations, a large inoculum population may 
provide sufficient genetic variation that individuals that can tolerate 
or prosper in the environment of introduction will be within the 
inoculum (Refs. 9 and 10). A biocontrol strategy that relies on the 
inoculum containing large numbers of microorganisms is thought to be 
successful because the introduced microorganisms may by sheer numbers 
have an advantage in reaching and filling available suitable 
microhabitats, availability of suitable habitat being a limiting factor 
for any population of organisms.
    The frequency with which organisms are released to an environment 
also affects whether an organism can establish. Frequent releases 
increase the likelihood that the microorganism will find sites 
favorable for establishment by increasing the total number of 
microorganisms placed in the environment and by increasing the 
probability that a microorganism will be introduced during a time 
favorable for establishment. This latter probability is related to 
factors such as the variations in temperature, moisture, light, and 
biota observed with seasonality. In other words, conditions favorable 
for establishment may exist at some period of time and not at others, 
and frequent application increases the probability that some 
individuals will be at the right place at the right time.
    3. Regulatory conditions to prevent microorganisms used for R&D 
from increasing beyond small quantities. EPA's proposed standards at 
Secs. 725.234 (containment and recordkeeping) and 725.235 (employee 
notification) are designed to reduce the probability of establishment 
by reducing the number and frequency of viable microorganisms emitted 
from a facility. The reduced probability of establishment increases the 
probability that a microorganism will remain a small quantity.
    EPA is proposing performance-based standards for this exemption. 
EPA's approach relies on the experience and judgement of the TQI, and 
EPA will not generally substitute its own judgement for that of the 
TQI. The approach recognizes that many different kinds of 
microorganisms displaying a wide range of characteristics could 
potentially be used in research, and that for certain microorganisms, 
emission of only a few viable individuals could cause an effect, while 
emission of large quantities of viable microorganisms of another type 
would not. It also recognizes that the type of controls (e.g., 
procedural, mechanical, and/or engineering) appropriate for one 
microorganism might have limited relevance to other microorganisms. EPA 
expects that the TQI will be cognizant of these factors when selecting 
containment and inactivation controls appropriate to the 
microorganism(s) being utilized.
    EPA does not believe the documentation requirements proposed for 
this exemption will be overly burdensome. EPA believes that for most 
cases, laboratory notebooks normally kept in the course of research 
will contain most of the information required by this proposal. Control 
measures selected could be indicated by reference to existing standards 
(e.g., one of the containment levels described in the NIH Guidelines). 
The TQI would simply record the reasons for choosing particular 
measures. With regard to the requirement that records document use of 
the selected controls, EPA is relying on the TQI to prepare and retain 
the appropriate degree of documentation. The amount of documentation 
would be correlated with the characteristics of the research 
microorganism and standard practices employed to address risk. Thus, 
documentation could range from general documentation of routine 
standard operating procedures, to specific notations in laboratory 
notebooks, to daily log entries for microorganisms that present the 
greatest risk concerns. If the NIH Guidelines are used as guidance, the 
TQI's notebook should indicate the level of containment recommended by 
the Guidelines and that this guidance was selected and used. EPA 
believes that persons following the NIH Guidelines would keep adequate 
records as part of normal procedures for informing their Institutional 
Biosafety Committee of the contained research.
    With respect to the certification requirement, many if not most 
research institutions have Institutional Biosafety Committees (IBCs) as 
required by the NIH Guidelines, or committees fulfilling a similar 
role. These committees are charged with assessing the containment 
selected by the investigator. EPA recognizes the value of this NIH 
system and would like to make its requirements consistent to the extent 
possible with such existing systems. The Agency also encourages the 
active use of such committees.
    The provision which indicates that EPA may request these records be 
sent to EPA for review (see Sec. 725.234(d)(3) of the regulatory text) 
is a restatement of the authority EPA has under TSCA section 11 to 
request and review information. It is also similar to provisions used 
by EPA in other exemptions. In the three exemptions from PMN reporting 
under part 723 that currently exist for traditional chemicals, one of 
the conditions for eligibility for the exemptions gives EPA access to 
the records demonstrating eligibility for the exemptions. EPA can 
require a company to produce the records upon EPA's written request.
    EPA does not plan to routinely review such records, although it may 
choose periodically to select some records for review. Should the 
institution or researcher receive a request for records review, the 
status of the research as exempt would not a priori be affected. 
Technical staff with experience reviewing TERA and MCAN submissions 
would examine the records. This provision allows EPA and the researcher 
to discuss what constitutes appropriate control measures and 
appropriate implementation and use. Under this provision, EPA may, upon 
review of the records, offer recommendations concerning what it 
considers appropriate control measures for the specific microorganisms 
used in the research. These recommendations would be non-binding. If 
EPA determines, however, that the control measures selected and used 
are so inadequate as to present an unreasonable risk, EPA can issue an 
order directed at modifying the control measures it finds problematic. 
Refusal to comply with an order would result in loss of eligibility for 
the exemption for the research in question. The researcher would then 
be subject to the notification requirements of TSCA section 5.
    EPA's criteria at proposed Secs. 725.234 and 725.235 are designed 
to reduce the probability of establishment by reducing the number of 
viable microorganisms emitted from a facility. However, EPA's proposed 
approach also takes into consideration factors such as the 
physiological condition of the microorganisms and how this might affect 
the ability of microorganisms to establish in the environment. 
Microorganisms used in laboratory research are more likely to be 
debilitated with regard to their ability to compete in the environment 
against wild type relatives. Thus, they may be less likely to prevail 
in the struggle in nature for limited resources. In general, incidental 
releases of microorganisms from research facilities are less likely to 
occur under conditions which favor the establishment of the 
microorganism. Incidentally released microorganisms may be 
physiologically debilitated by aerosolization or other process 
procedures, and may be less likely to find an environment that favors 
their survival and persistence than those microorganisms that are 
specifically tested in an environment where they are intended to 
survive, at least long enough to perform a specific function.
    EPA recognizes that parts of the rationale offered for exempting 
research conducted under the conditions set forth in proposed 
Sec. 725.234 can be applied to some small-scale field tests involving 
microorganisms. The rationale cannot, however, be applied to small 
scale field tests as a class. Microorganisms intentionally tested in 
the environment are more likely to be acclimated to the environment 
into which they are introduced, be physiologically fit enough to be 
competitive in that environment for a significant period of time, and 
be placed in an area suitable for growth and persistence. Because of 
the lessons learned with biocontrol microorganisms, researchers will 
purposefully apply large enough numbers to ensure that the 
microorganism persists long enough and competes well enough to perform 
the function the researcher intends to study. In general, the 
probability that these types of microorganisms, used under these 
conditions, will establish is thus higher than the probability 
associated with incidental emissions from facilities employing EPA's 
proposed criteria.
    4. Alternative reasons for the research exemption. An alternative 
rationale would hold that the small quantities exemption in section 
5(h)(3) does not apply to microorganisms as a class, because some 
microorganisms, whether they are released through intentional testing 
or incidental emission, can establish even though the initial inoculum 
is very small. For some microorganisms, a single microorganism may be a 
sufficient inoculum for establishment to occur. Thus, for 
microorganisms as a class, there can be no concept of ``small 
quantities'' similar to that envisioned for other chemicals.
    EPA would find, however, that research conducted under the criteria 
specified in Secs. 725.234 and 725.235 could be exempted under TSCA 
section 5(h)(4). EPA's authority under TSCA Sec. 5(h)(4) is discussed 
in Unit III.C. of this preamble. In situations where the EPA criteria 
at Secs. 725.234 and 725.235 are followed, EPA believes that the 
resulting reduction in the number of microorganisms emitted from R&D 
facilities will reduce the probability that a microorganism will 
establish in the environment. This reduced probability of establishment 
leads directly to a reduction in risk. If a microorganism does not 
establish, its ability to present risk is far less likely to be 
expressed. If the microorganism is not able to establish, any adverse 
effects that might be associated with that microorganism will probably 
be spatially and temporally limited.
    EPA recognizes that some research activities may present special 
considerations; e.g., when the research utilizes microorganisms that 
can successfully establish from a very small inoculum. In such cases, 
incidental emission from the facility may have to be much more 
stringently controlled to reduce risk. EPA believes that its 
requirement that a technically qualified individual (TQI) select and 
validate procedures appropriate to the microorganism addresses this 
concern. That person should select, validate, and follow procedures 
that would ensure that insufficient numbers of viable microorganisms 
are emitted from the facility for establishment to occur.
    EPA believes that any potential risk presented by incidental 
releases from research facilities that might occur, even when its 
criteria for reducing the number of microorganisms emitted from the 
facility are followed, is outweighed by the benefits to society of 
biotechnology research. EPA can use its limited resources, which 
otherwise would be used to review these low risk research activities 
for microorganisms, for reviewing higher risk activities and 
microorganisms. Industry, by having this exemption, can develop and 
test microorganisms in the early stages of the product development 
process (e.g., laboratory) without having to be reviewed by EPA. This 
would reduce the time and cost for industry in developing new products. 
More time and resources could be allotted for actual R&D and less time 
and resources allotted to EPA notifications. This should assist the 
development of this industry and the emergence of new, useful products, 
and thus not present an unreasonable risk of injury to human health and 
the environment.
    5. Alternative methods of reducing the number of microorganisms 
emitted. EPA believes its proposed approach to reducing the number of 
microorganisms emitted from research facilities is preferable to more 
prescriptive approaches which have been suggested. The suggested 
approaches include setting a specific numerical standard for the number 
of microorganisms that might be incidentally released to the 
environment from a research facility, prescribing a single standard 
based on one of the containment levels described in the NIH Guidelines, 
or an approach wherein several increasingly stringent levels of 
containment are described and specific microorganisms are matched to 
specific levels. These three approaches would be complex and unwieldy 
to implement. Because of their prescriptive nature, such approaches 
would result in EPA regulating the containment standards rather than 
exempting the research. This would unnecessarily restrict research 
contrary to the intent of TSCA. Each change to a prescriptive standard 
would have to be incorporated into the standards through rule 
amendments or variance procedures. Establishing prescriptive standards 
could restrict advances in technology for controlling microorganisms 
and stifle individual initiative at the research level.

C. Section 5(h)(4) Exemptions

    1. Introduction--a. Statutory background. Section 5(h)(4) of TSCA 
provides that EPA may exempt by rule the manufacture of any new 
chemical substance from all or part of the requirements of section 5, 
if it is determined that activities involving the substance will not 
present an unreasonable risk of injury to health or the environment. A 
section 5(h)(4) rule must be promulgated under the procedures set forth 
in TSCA sections 6(c)(2) and (3), which generally require preparation 
of a rulemaking record and an administrative hearing. EPA is proposing 
to use section 5(h)(4) to support various exemptions from the 
notification requirements of the rule.
    The term ``unreasonable risk'' is not defined in TSCA. Section 6(c) 
of TSCA lists considerations for determining whether a chemical 
substance presents an unreasonable risk for purposes of promulgating 
regulations under TSCA section 6. These considerations include the 
effects of the substance on human health and on the environment and the 
magnitude of exposure to the substance, the benefits of the substance 
for various uses, the availability of substitutes for such uses, and 
the reasonably ascertainable economic consequences of the potential 
regulatory action, considering effects on the national economy, small 
business, technological innovation, the environment, and public health. 
EPA believes it is reasonable to consider these factors in determining 
whether a risk is unreasonable under section 5(h)(4).
    TSCA offers no further direct guidance on what constitutes 
unreasonable risk. In particular, TSCA does not discuss how each of the 
section 6(c) considerations are to be weighed in relation to each 
other. The legislative history, therefore, needs to be considered. The 
House Report (H.R. Rep. 94-1341, 94th Cong., 2d Sess. at 13-15, 32) 
provides the most useful pertinent explanation. First, the standard 
under TSCA is ``unreasonable'' risk, not a decision to eliminate all 
risk (House Report at 15). For an activity that is of some value to 
society, some level of risk may be acceptable. With respect to section 
5(h)(4), granting an exemption does not require a showing that there 
will be no risk, only that there will be no unreasonable risk.
    The House Report states that the unreasonable risk standard cannot 
be defined in precise terms but, instead, requires exercise of judgment 
by the decisionmaker. The House Report describes the finding of 
unreasonable risk as involving a balancing of the probability that harm 
will occur, and the magnitude and severity (potential consequences) of 
that harm, against the effects (social and economic) of proposed action 
on society.
    According to the House Report, these evaluations of harm often must 
be based on considerations of ``scientific theories, projections of 
trends from currently available data, modeling using reasonable 
assumptions, and extrapolations from limited data'' (House Report at 
32). The unreasonable risk standard recognizes that, as a practical 
matter, all the scientific evidence is uncertain to some degree and 
that EPA can consider such factors as the strength of the evidence on 
toxicity, the nature of the effects that may occur (e.g., death vs. 
reversible effects), and the likely numbers of individuals exposed and 
the levels of exposure.
    The House Report points out that the unreasonable risk standard is 
flexible enough to allow EPA to calibrate the stringency of a 
regulatory measure to the levels of risks and benefits. Thus, a testing 
rule, because it does not deprive the public of the benefits of a 
chemical, requires a lesser showing of harm compared to a rule which 
may remove a substance from the market or impose other restrictions on 
its availability. Similarly, a stronger showing would be required to 
ban an activity than to impose lesser restrictions on use or a 
requirement, such as labelling, that does not restrict directly.
    The greater the probability and the more severe the potential harm 
presented by an activity EPA may allow, the less likely a no 
unreasonable risk finding can be made. Similarly, the greater the 
benefit of the activity, the greater the risk to be tolerated. 
Determinations of whether an exemption should be partial or full will 
depend on the probability and severity of the harm and the benefits to 
be derived from the activity. Less restrictions should apply if there 
are substantial benefits from the activity and the probability of harm 
appears to be lower or the consequences are of low concern.
    b. Summary of section 5(h)(4) exemptions. EPA is proposing to use 
its authority under TSCA section 5(h)(4) to establish six separate 
types of exemptions. These are partial exemptions that involve limited 
reporting and/or recordkeeping for new microorganisms that meet the 
eligibility requirements of the specific exemptions. Five of these 
exemptions specifically relate to R&D activities. The sixth case is a 
tiered exemption for general commercial use.
    Because each exemption involves a different set of issues, each 
exemption requires a different weighing of risks and product benefits. 
The remainder of this unit sets out the no unreasonable risk findings 
for each of the exemptions. For each exemption, a review of the 
relevant scientific risk considerations is followed by a discussion of 
the social and economic benefits resulting from microbiological 
products. The extent to which both risks and benefits are considered is 
dependent on the breadth of the exemption.
    2. Alternative finding of no unreasonable risk for microorganisms 
used for R&D in contained structures. The reasoning for this 
alternative finding relies on the factors discussed in Unit III.B. of 
this preamble for research that meets the criteria at proposed 
Secs. 725.234 and 725.235 for R&D conducted in contained structures. 
See Unit III.B. of this preamble for a full discussion of the rationale 
for exempting research in contained structures.
    3. Deferral to other Federal authorities for oversight of R&D. Unit 
II.D. of this preamble describes a proposed exemption from this 
regulation for research controlled by other federal authorities. This 
section provides EPA's reasons for establishing this exemption. The 
exemption is based on the general policy that TSCA should not apply to 
research adequately overseen by other federal authorities.
    TSCA jurisdiction is discussed in Unit I.C. of this preamble. 
Generally microorganisms controlled by other Federal agency 
authorities, other than those microorganisms regulated under FIFRA or 
FDA authorities, are also subject to TSCA. Agencies, such as the Animal 
and Plant Health Inspection Service (APHIS) of the U.S. Department of 
Agriculture (USDA), have regulatory authority that overlaps TSCA 
authority for microorganisms. Research subject to TSCA may also be 
funded by Federal agencies, such as the Department of Defense (DOD), 
the Department of Energy (DOE), the National Institutes of Health 
(NIH), the National Science Foundation (NSF), USDA's APHIS or its 
Office of Science and Education (S&E), or EPA's own Office of Research 
and Development (EPA/ORD).
    On November 23, 1976, all Federal agencies represented on the 
Federal Interagency Committee endorsed the NIH Guidelines. Departments 
which support or conduct laboratory rDNA research agreed to abide by 
the Guidelines in June 1983 (48 FR 24577). Because of the 1983 
agreement, as a condition for Federal funding of rDNA laboratory 
research, institutions must ensure that all rDNA research conducted at 
or sponsored by the institution, regardless of the source of the 
funding, complies with the Guidelines.
    a. Finding of no unreasonable risk for R&D in contained structures 
subject to the authority of other Federal agencies. This proposed rule 
would provide an exemption for research in contained structures 
(principally laboratories) covered by the NIH Guidelines. EPA considers 
the NIH Guidelines to provide the primary standard for laboratory 
research. EPA's rules are designed to provide complementary oversight 
of those activities not covered by NIH. As a result, EPA is proposing a 
complete exemption under TSCA section 5(h)(4) for research on new 
microorganisms in contained structures, if the researcher is required 
to comply with the NIH Guidelines. This may be achieved through direct 
regulatory authority or through requiring recipients of Federal funds 
to comply with the NIH Guidelines. Without this exemption, the 
recordkeeping and employee notification requirements of proposed 
Secs. 725.234 and 725.235 would apply to this research. EPA's summary 
analysis of the NIH Guidelines may be found in the docket which 
supports this rulemaking.
    EPA proposes under TSCA section 5(h)(4) to exempt from the 
requirements described in proposed Secs. 725.234 and 725.235 the 
manufacturers, producers and importers of new microorganisms for R&D in 
contained structures, if the research is regulated or funded by a 
Federal agency which has agreed to abide by the NIH Guidelines.
    The pertinent parts of EPA's regulations applying to R&D in 
contained structures are Sec. 725.234(b) and (d). They require a 
technically qualified individual (TQI) to maintain documentation that 
describes the selection of containment and inactivation procedures and 
ensures the procedures are followed. The TQI's selections must be 
approved and certified by an authorized official of the institution 
conducting the experiment (Sec. 725.234(d)(2)). EPA may request the 
records, review containment/inactivation controls and may order changes 
in containment/inactivation procedures (Sec. 725.234(d)(3) and (d)(4)).
    These provisions are designed to complement the NIH Guidelines and 
extend their benefits, without imposing an overly rigid regulatory 
regime. EPA's regulation is in the same spirit as the NIH Guidelines in 
that it is also based on the fact that all conceivable experiments 
cannot be foreseen and that it is the responsibility of the 
experimenting institution to devise appropriate containment. Like NIH, 
EPA emphasizes the importance of the motivation and good judgment of 
the investigators.
    Because the NIH Guidelines are very well entrenched in the research 
community, EPA expects that the procedures chosen by the TQI will very 
closely follow the Guidelines. In addition, any EPA review of records 
will rely heavily on the Guidelines. Thus, by establishing the 
provisions of proposed Sec. 725.234(d), EPA would effectively apply 
Guideline principles to those institutions, primarily commercial 
facilities, that are not required to abide by them. This would 
complement the NIH request for voluntary compliance.
    Further, the NIH Guidelines apply directly only to those 
microorganisms, and categories of microorganisms, that have been listed 
in the Guidelines and, in particular, Guideline Appendices A through F. 
Other microorganisms would require specific review by NIH. EPA 
regulations extend the benefits of the NIH Guidelines by effectively 
applying their principles to microorganisms other than those 
specifically mentioned in the Guidelines.
    At the same time, by not incorporating the Guidelines directly into 
regulations, EPA would avoid overly rigid adherence to Guidelines that 
are, themselves, meant to be flexible. EPA, however, retains sufficient 
control to protect against risk by the review procedures in proposed 
Sec. 725.234(d)(3) and (d)(4).
    Requiring researchers to adhere to the proposed requirements of 
Secs. 725.234 and 725.235 as well as to the requirements of these other 
federal authorities would be a duplication of oversight and enforcement 
that would unnecessarily restrict potentially beneficial research 
without any incremental reduction in potential risk. Thus, there would 
be no increase in risk from removing the TSCA section 5 restrictions 
placed on contained structure R&D. Further, costs will be reduced, 
because there would be no costs incurred in complying with TSCA. R&D 
would be encouraged without an attendant increase in risk. Therefore, 
the risks of exempting this research from the TSCA section 5 contained 
structure R&D restrictions are far outweighed by the costs saved. 
Accordingly, EPA finds there will be no unreasonable risk from this 
exemption.
    b. Federal agency R&D subject to TERA reporting. EPA has also 
considered how it might use its TSCA section 5(h)(4) exemption 
authority to minimize duplicative reviews of environmental release 
tests that are also subject to other Federal agencies. EPA has 
determined that a different exemption process should apply to 
experiments in the environment than to contained experiments. While the 
NIH Guidelines are recognized as a standard for contained R&D, the same 
situation does not pertain to R&D activities involving releases to the 
environment. Accordingly, EPA is planning to propose the procedures 
outlined below for exemptions from the TERA process for deliberate 
release experiments reviewed by other Federal agencies.
    With agencies that have clear regulatory authority, EPA would 
propose to exempt from TSCA section 5 requirements intentional 
environmental testing of new microorganisms and to defer to the other 
Federal agency's review, when EPA determines that the other Federal 
agency's review addresses criteria equivalent to those which would be 
evaluated under TSCA section 5. When EPA develops such an exemption 
involving deferral to another Federal agency, it will propose the 
exemption using notice and comment rulemaking. EPA is currently working 
with USDA-APHIS to develop an exemption for R&D field tests reviewed by 
APHIS under the Federal Plant Pest Act and the Plant Quarantine Act and 
implementing regulations at 7 CFR part 340 and hopes to include such an 
exemption when the rule is promulgated.
    4. Finding of no unreasonable risk for TERA approval of new 
microorganisms--a. Background. EPA recognizes that many small-scale 
tests will not present unreasonable risks and that requirements 
restricting R&D could stifle innovation contrary to the intent of TSCA. 
Therefore, under section 5(h)(4) EPA is proposing to conditionally 
exempt from MCAN notification R&D involving certain new microorganisms. 
The exemption is conditional, since researchers must submit a TERA.
    EPA's current experience with reviewing PMNs for microorganisms 
used for R&D in the environment under the 1986 Policy Statement has 
indicated that EPA could more efficiently review these activities. 
While the current process provides an adequate mechanism, R&D 
activities present a very different risk assessment situation than 
general commercial use. Differences in exposure, the ability to apply 
procedures for controlling routes of exposure or dissemination and the 
procedures for controlling potential risks, and the need for 
flexibility in R&D comprise different risk assessment scenarios than 
found in general commercial use. As a result, in light of these 
different scenarios, a more straightforward and flexible approach to 
reviewing experiments for new microorganisms is indicated. The TERA 
provisions of this proposed rule will provide such an approach.
    A TERA provides for submission of information commensurate with the 
nature of the R&D process, because the review is focused on a specific 
R&D activity. Therefore, not as much information is required compared 
to a MCAN. For example, persons who submit a TERA would not have to 
include information on all commercial manufacture, processing, 
transport, use, and disposal activities that may involve the new 
microorganism as is the case for a MCAN.
    The more flexible deadlines and procedures for the TERA would avoid 
unnecessary delays or restrictions on experiments. TSCA imposes a 90-
day waiting period for section 5(a)(1) screening; and persons who 
submit MCANs must wait at least 90 days before an activity can begin, 
even if EPA should determine no unreasonable risk is posed by the 
activity before the 90-day review period expires. A similar waiting 
period may not be appropriate for experiments when more rapid decisions 
can be made. If TERA review shows that an experiment poses little or no 
risk, EPA could notify the submitter to proceed at any time during the 
review period prior to expiration of the review clock.
    b. No unreasonable risk determination. EPA has decided that case-
by-case review is required to determine the potential risk presented by 
a microorganism which may establish in the environment during the 
course of a field trial. The review would allow EPA to determine if it 
would be necessary to set limitations to minimize the probability of 
establishment and dissemination in the environment. Microorganisms 
intentionally tested in the environment are more likely to be 
acclimated to the environment into which they are introduced, be 
physiologically fit enough to be competitive in that environment for a 
significant period of time, and be placed in an area suitable for 
growth and persistence. Researchers generally apply large numbers of 
microorganisms to ensure that they persist long enough and compete well 
enough to perform the function the researcher intends to study. This 
fact increases the probability that microorganisms used under these 
conditions could establish and possibly pose a risk or result in 
significant exposure. Therefore EPA has concluded that R&D which 
involves intentional testing of microorganisms in the environment 
should be subject to some review.
    EPA has balanced a number of considerations to determine that 
experiments reviewed under a TERA will not present an unreasonable risk 
to health or the environment and should be exempt from MCAN 
requirements. First, TERA review should result in no greater risks than 
those that might occur as a result of the MCAN process, because the no 
unreasonable risk criteria for approval are the same for either 
process. Second, TERA review may even reduce risks in some instances by 
allowing EPA to focus resources on activities that may pose the 
greatest potential for risk. Third, TERA review will reduce reporting 
costs by eliminating Agency need for information and procedures that 
are unnecessary for R&D. Fourth, when compared to the MCAN process, 
TERAs should encourage technological innovation and have a beneficial 
effect on small businesses engaged in R&D utilizing new microorganisms.
    5. Finding of no unreasonable risk for microorganisms proposed for 
exemption from TERA reporting. EPA recognizes that some field 
experiments with new microorganisms do not need to be reviewed at all. 
EPA therefore intends to exempt from review some R&D experiments with 
certain new microorganisms. EPA will, however, still review any general 
commercial uses of these new microorganisms through the MCAN process. 
The no unreasonable risk finding for exemption from TERA reporting is 
based on the interaction of three principal criteria addressing the 
recipient species, the introduced genetic material, and procedures for 
limiting exposure during experimental use. The three criteria must be 
considered in concert, because any potential concerns raised in one set 
of criteria may be balanced or compensated by other criteria. These 
criteria are discussed in more detail in Unit III.C.7. of this 
preamble.
    EPA requests comment on whether this approach should be used to 
exempt from TERA screening certain new microorganisms. EPA is proposing 
certain intergeneric strains of Bradyrhizobium japonicum and Rhizobium 
meliloti as candidates for exemption from TERA review, based on reviews 
of voluntary PMNs submitted under the 1986 Policy Statement and field 
test data generated in these field trials. Persons possessing 
information which they believe would support an exemption from TERA 
reporting for other new microorganisms may use the procedures in 
proposed Sec. 725.67 to apply for such an exemption.
    EPA proposes to list Bradyrhizobium japonicum and Rhizobium 
meliloti as acceptable recipient species. Both are well-characterized 
taxonomically and have been used in the environment for over 80 years 
to improve nitrogen fixation in specific agricultural crops. There is 
extensive information on these two species documenting the lack of 
adverse effects in the environment, and no reports exist that they are 
pathogenic to humans or animals. In addition, EPA has reviewed field 
test data from several experiments which have demonstrated that the 
intergeneric strains are similar to the unmodified parental strains in 
colonization, survival, nodulation and effects on plant growth. The 
public dockets pertaining to the reviews of B. japonicum (six strains: 
P88-1275 through 1278, and P89-340 and 341) and R. meliloti (18 
strains: P87-568 through 570, P88-1115 through 1122, P89-280, P90-339, 
and P92-399 through 403), along with the field test data, are 
incorporated into the docket for this rulemaking. These strains were 
modified in antibiotic resistance traits, and some were modified for 
nitrogen fixation traits as well. In the course of these reviews, EPA 
evaluated general and specific information in the open scientific 
literature concerning these species, and BSAC subcommittees were 
convened to discuss general issues associated with the proposed R&D 
experiments with these strains.
    Modification of traits, the second criterion, limits the source of 
the introduced genetic material to the genera of Rhizobium and 
Bradyrhizobium but allows the introduction of antibiotic resistance 
traits from any source organism. In addition, the introduced genetic 
material must be poorly mobilizable. The introduction of genetic 
material for traits other than antibiotic resistance is limited to 
Bradyrhizobium and Rhizobium species, because EPA is most familiar with 
these two genera.
    Based on the results of the field tests with these strains, EPA 
proposes to exempt the use of well-characterized, limited in size, and 
poorly mobilizable antibiotic resistance markers in Bradyrhizobium 
japonicum and Rhizobium meliloti. EPA believes that there would be no 
significant risk resulting from small-scale field tests with the 
resulting microorganisms containing antibiotic resistance, because 
broad antibiotic resistance already exists in naturally occurring 
microorganisms of these two species (as demonstrated in the data 
submitted for PMNs P88-1115 (rhizobia) and P88-1275 (bradyrhizobia). In 
addition, higher levels of antibiotic resistance can be easily induced 
in these microorganisms by mutation or selection. EPA requests comment 
on the appropriateness of exempting antibiotic resistance traits.
    EPA is proposing that these exemptions would only apply to test 
sites of 10 acres or less. This test area limit for Bradyrhizobium 
japonicum and Rhizobium meliloti is based on the field data reviewed by 
EPA which show that such releases have remained small-scale, with the 
modified strains exhibiting survival and persistence similar to their 
unmodified parental strains. The TQI must select appropriate methods to 
limit dissemination of these modified rhizobial species in order to 
maintain the small-scale nature of the field tests. Also, this proposal 
is based on the lack of adverse effects observed in humans and animals 
resulting from use of these naturally occurring rhizobial species.
    EPA is proposing to exempt intergeneric strains of these two 
rhizobia species, in order to facilitate research using these 
microorganisms and to encourage development of products that could 
increase crop productivity while decreasing dependance on chemical 
fertilizers. These experiments could generate important information 
that will increase understanding of the environmental fate of 
intergeneric microorganisms. Information from these field tests would 
advance the understanding of microbial ecology, which could facilitate 
review of commercial products. The possible risks due to exempting 
these two rhizobia species from review at small-scale will be balanced 
by the innovation and development of safer, environmentally sound 
products to promote crop production.
    6. Finding of no unreasonable risk for specific alternative 
exemption for low risk field tests. Unit II.D. of this preamble 
describes an alternative exemption from TERA reporting for certain R&D 
field tests. While EPA acknowledges that parts of the rationale offered 
in Unit III.B. of this preamble for exempting research conducted under 
the proposed contained structures exemption could be applied to some 
small-scale field tests involving microorganisms, EPA does not believe 
that the rationale can be applied to small-scale field tests as a 
class. Therefore, it was suggested that EPA define a class of small-
scale field tests which would be expected to pose low risks and be 
exempt from TERA reporting. The no unreasonable risk finding for this 
alternative exemption from TERA reporting is based on the interaction 
of three primary criteria which consider the safety of the parent 
microorganism, the role of the traits that have been modified, and the 
scale of the field tests. If the parent microorganism is shown to have 
a history of safe use, introduced genetic material meeting the 
specified criteria would be unlikely to significantly increase the 
potential for adverse effects. EPA would expect that TQIs would use the 
criteria discussed in III.C.7. of this preamble for the recipient 
microorganism and the introduced genetic material as guidance in 
determining that their new microorganisms would be eligible for this 
exemption. As in the contained structures exemption for R&D, EPA is 
relying on the experience and judgement of the TQI to select 
appropriate methods to limit dissemination of the new microorganisms in 
order to maintain the small-scale nature of the field tests. Reliance 
on the judgement of the TQI is discussed further in Unit III.B. of this 
preamble. EPA believes that the criteria it has specified circumscribe 
a category of field tests which can be considered low risk. In 
addition, should EPA receive a notice for a planned field test which 
did not appear to be low risk, EPA could require the submission of a 
TERA in order to review more completely the proposal.
    EPA believes that the field tests potentially eligible for this 
alternative exemption could generate important information which will 
generally advance the understanding of microbial ecology and 
specifically facilitate EPA's review of intergeneric microorganisms. 
The low risks posed by the field tests will be balanced by benefits in 
the form of reduction in reporting burden for researchers and the 
encouragement of innovation in the development of environmentally sound 
products. EPA would like to receive public comment on whether the 
benefits of this exemption outweigh the potential risks posed by small-
scale field tests eligible for the exemption.
    Although field tests which meet the proposed criteria would be 
considered to pose low risks, additional concerns could be raised for 
unlimited uses of the same microorganisms at the general commercial use 
stage. Once development of these microorganisms moves beyond R&D to 
general commercial use, they would be subject to the MCAN reporting 
requirements discussed in Unit II.C. of this preamble.
    7. Finding of no unreasonable risk for new microorganisms eligible 
for tiered commercial use exemption. EPA recognizes that some 
microorganisms present a low risk when used under specific conditions 
at general commercial use. Therefore, EPA is proposing expedited 
processes for certain microorganisms at the general commercial use 
stage. The requirements and processes for the Tier I and Tier II 
exemptions are discussed in Unit II.C. of this preamble. The criteria 
for Tier I and Tier II exemptions address: (1) The recipient 
microorganism; (2) the introduced genetic material; and (3) performance 
based standards for minimizing the numbers of microorganisms emitted 
from the manufacturing facility.
    To evaluate the potential for unreasonable risk to human health or 
the environment in developing these exemptions, EPA focused primarily 
on the characteristics of the recipient microorganisms. If the 
recipient is shown to have little or no potential for adverse effects, 
introduced genetic material meeting the specified criteria would not 
likely significantly increase potential for adverse effects. As further 
assurance that risks would be low, EPA is also specifying procedures 
for minimizing numbers of organisms emitted from the facility. When 
balanced against resource savings for society and expected product 
benefits, these exemptions will not present unreasonable risks.
    a. The recipient microorganism. Six criteria were used to determine 
eligibility of recipient microorganisms for the tiered exemption. 
First, it should be possible to clearly identify and classify the 
microorganism. Available genotypic and phenotypic information should 
allow the microorganism to be assigned without confusion to an existing 
taxon which is easily recognized. Second, information should be 
available to evaluate the relationship of the microorganism to any 
other closely related microorganisms which have a potential for adverse 
effects on human health or the environment. Third, there should be a 
history of safe commercial use for the microorganism. Fourth, the 
commercial uses should indicate that the microorganism products might 
be subject to TSCA jurisdiction. Fifth, studies are available which 
indicate the potential for the microorganism to cause adverse effects 
on human health and the environment. Sixth, studies are available which 
indicate the survival characteristics of the microorganism in the 
environment. EPA requests comment on whether these are the appropriate 
criteria to consider to determine the eligibility of recipient 
microorganisms for the tiered exemption. After each microorganism was 
reviewed using the six evaluation criteria, a decision was made to 
place the microorganism on the list in proposed Sec. 725.420. Summaries 
of the individual risk assessments, are discussed below. The full risk 
assessments for the recipient microorganisms are in the docket for this 
proposed rulemaking.
    (i) Acetobacter aceti is an obligate aerobic bacterium naturally 
found in the restrictive niche of fermenting fruit, where it can 
tolerate and utilize ethanol as a nutrient. This species has no 
recorded pathogenicity on plants, humans, or animals and has a history 
of safe industrial use. A. aceti is well-defined taxonomically and 
clearly distinguished from other Acetobacter species known to cause the 
browning of processed fruit. While it can be expected to survive in the 
environment, A. aceti is unlikely to cause any significant 
environmental effects.
    (ii) Aspergillus niger is an asexual fungus commonly found 
degrading organic matter in nature. This organism has a history of safe 
use for the production of citric acid and several enzymes. It has been 
shown to be an opportunistic human pathogen and to damage several 
species of plants. While production of certain mycotoxins has been 
associated with strains of A. niger, companies have been using 
naturally occurring strains of A. niger to produce a variety of 
products for many years without reports of toxic effects of workers. 
The limited in size constraints as well as the restriction on 
vertebrate toxins imposed on introduced genetic material by the 
criteria for the tiered exemption should reduce the likelihood of 
increased production or exposure to malformins A and C, the two most 
potent mycotoxins potentially produced by A. niger strains. In general, 
the restrictions placed on the introduced DNA and containment mean that 
the recombinant A. niger strains eligible for the tiered exemption 
should pose no greater risks than naturally occurring strains of A. 
niger.
    (iii) Aspergillus oryzae is an asexual fungus found in nature and 
used for hundreds of years in the production of soy sauce, miso and 
sake without recorded incidents. This fungus has no reported adverse 
effects on either plants or animals. It has been suggested that genetic 
engineering of A. oryzae might inadvertently produce an aflatoxigenic 
strain. Naturally occurring strains of A. oryzae are not known to 
produce aflatoxins; however, some scientists believe that A. oryzae is 
a domesticated version of A. flavus and may possess dormant genes for 
aflatoxin production. It is likely that companies have already been 
using genetically modified strains of A. oryzae, but these strains have 
not yet met the PMN reporting requirements, that is, they are not 
intergeneric. The limitations placed by the tiered exemption on the 
introduced genetic material, in particular the well-characterized and 
limited in size restrictions, should reduce the likelihood that any 
sequences relating to aflatoxin production could be introduced. The 
containment requirements would limit exposure to any mycotoxins 
produced. In addition, A. oryzae does not colonize humans. In general, 
the restrictions placed on the introduced genetic material and 
containment mean that the recombinant A. oryzae strains eligible for 
the tiered exemption should pose no greater risks than naturally 
occurring strains of A. oryzae.
    (iv) Bacillus licheniformis is an aerobic sporeforming bacterium 
that is well defined taxonomically. It can be readily isolated from the 
environment, where it persists primarily as endospores. Many strains 
have been tested and shown to have no adverse effects on humans, 
animals or plants. B. licheniformis has been reported as an 
opportunistic pathogen in livestock; however, it has never been 
diagnosed as a causal agent. B. licheniformis has a history of safe use 
in large-scale fermentation production of specialty chemicals and 
substances such as citric acid and detergent enzymes. Although the 
majority of experience with industrial fermentations employing B. 
licheniformis is with asporogenic strains, all strains of this 
microorganism are being recommended for the tiered exemption.
    (v) Bacillus subtilis is an aerobic sporeforming bacterium which is 
not completely defined at either the genus or species level. This 
species is commonly found in nature, particularly in terrestrial 
environments. Many strains have been tested and shown to have no 
adverse effects on humans, animals or plants. Reports of B. subtilis 
acting as an opportunistic pathogen are few in number and have not been 
well substantiated. B. subtilis has a history of safe use in large-
scale fermentation production of specialty chemicals and enzymes and 
even as a source of single cell protein for human consumption in Asia. 
Although the majority of experience with industrial fermentations 
employing B. subtilis is with asporogenic strains, all strains of this 
microorganism are being recommended for the tiered exemption.
    (vi) Clostridium acetobutylicum is an obligate anaerobic endospore-
forming bacterium which has been isolated from soils, sediments, well 
water, and from animal and human feces. Various strains of C. 
acetobutylicum have a history of safe use industrially or in research 
for the production of butanol and acetone from various feedstocks. 
While C. acetobutylicum may survive in the environment, it is not 
likely to cause any significant environmental effects. Although the 
current taxonomic classification of Clostridium species is not well-
defined, C. acetobutylicum can be distinguished from closely related 
species which are known to be human pathogens. In general, the 
restrictions placed on the introduced genetic material and containment 
mean that the recombinant C. acetobutylicum strains eligible for the 
tiered exemption should pose not greater risks that the naturally 
occurring strains of C. acetobutylicum which have been used in industry 
without reports of adverse effects to workers or the environment.
    (vii) Escherichia coli K-12 is a strain which is well defined 
taxonomically, although the genus Escherichia as a whole is not. E. 
coli K-12 strains can be readily distinguished from those close 
relatives that are pathogens. E. coli K-12 is a debilitated bacterium 
which does not normally colonize the human intestine. It has also been 
shown to survive poorly in the environment, has a history of safe 
commercial use, and is not known to have adverse effects on humans, 
microorganisms, or plants. Although some K-12 substrains produce low 
levels of toxins, toxin expression by these substrains is mitigated by 
E. coli K-12's poor survival in the environment and its inability to 
colonize normal human or animal hosts.
    (viii) Penicillium roqueforti is an asexual fungus which decomposes 
organic materials in nature. Most strains of P. roqueforti, including 
those used in cheese production, have been shown capable of producing a 
variety of mycotoxins. P. roqueforti's long history of use in the 
production of blue cheese has shown no adverse effects. P. roqueforti 
is generally considered to be a benign organism, but it does raise 
concerns because of its ability to produce mycotoxins under certain 
conditions. Despite these concerns, the organism has a history of use 
without noted reports of adverse effects to workers or the environment. 
In general, the restrictions placed on the introduced genetic material 
and containment mean that the recombinant P. roqueforti strains 
eligible for the tiered exemption should pose no greater risk than 
naturally occurring strains of P. roqueforti.
    (ix) Saccharomyces cerevisiae is a yeast that occurs commonly in 
the environment. Although it is not well defined taxonomically and 
survives well in the environment, it has a history of safe use in the 
commercial production of many products (e.g., beer). Further, it is not 
known to cause pathological effects on humans, plants, or animals. S. 
cerevisiae has no known effects on microorganisms, other than possible 
effects on strains of its own species.
    (x) Saccharomyces uvarum is a yeast capable of fermenting a variety 
of sugars into ethanol. S. uvarum has a long history of safe use in 
production of alcoholic beverages and industrial ethanol. Although it 
is expected to survive in the environment, it is not expected to cause 
any adverse environmental effects. While S. uvarum has been used 
industrially for years, specific strains have not been distinguished.
    b. The introduced genetic material. In order to qualify for either 
Tier I or Tier II exemption, any introduced genetic material must be 
limited in size, well-characterized, free of certain nucleotide 
sequences, and poorly mobilizable.
    (i) Limited in size. Introduced genetic material must be limited in 
size to those segments required to perform the intended function, as 
described at proposed Sec. 725.421(a). This criterion reduces 
uncertainty by excluding the introduction into a recipient of 
extraneous and potentially uncharacterized genetic material. The 
requirement that the regulatory sequences permit the expression solely 
of the structural gene(s) of interest reduces risk by preventing 
expression of genes downstream of the inserted genetic material. The 
limitation on the vector sequences that are components of the 
introduced genetic material prevents the introduction of novel traits 
beyond those associated with the gene(s) of interest. The overall 
result of the limited in size criterion is improved ability to predict 
the behavior of the resulting microorganism. EPA requests comment on 
the usefulness of this criterion in reducing uncertainty about the 
behavior of the new microorganism and any difficulties researchers may 
have in isolating the genetic material required to perform the intended 
functions.
    (ii) Well-characterized. The requirement at proposed 
Sec. 725.421(b) that the introduced genetic material be well-
characterized also contributes to improved ability to predict the 
behavior of the resulting microorganism. Well characterized includes 
knowledge of the function of the introduced sequences and the 
phenotypic expression associated with the introduced genetic material. 
Genetic material which has been examined at the restriction map or 
sequence level, but for which a function or phenotypic trait has not 
yet been ascribed, is not considered well-characterized.
    Well-characterized would include knowing whether multiple reading 
frames exist within the operon. This relates to whether more than one 
biological product might be encoded by a single sequence, and addresses 
the possibility that a modified microorganism could display unpredicted 
behavior should such multiple reading frames exist and their action not 
be anticipated.
    (iii) Free of certain sequences. In addition to improving the 
ability to predict the behavior of the modified microorganism, the 
well-characterized requirement ensures that segments encoding for 
either part or the whole of the toxins listed at proposed 
Sec. 725.421(d) would not inadvertently be introduced into the 
recipient microorganism (Refs. 11 and 12).
    The toxins listed at proposed Sec. 725.421(d) are polypeptides of 
relatively high potency. Other types of toxins (e.g., modified amino 
acids, heterocyclic compounds, complex polysaccharides, glycoproteins, 
and peptides) are not listed for two reasons. First, their toxicity 
falls within the range of moderate to low. Second, these types of 
toxins generally arise from the activity of a number of genes in 
several metabolic pathways (multigenic).
    In order for a microorganism to produce toxins of multigenic 
origin, a large number of different sequences would have to be 
introduced and appropriately expressed. It is unlikely that all of the 
genetic material necessary for metabolizing multigenic toxins would be 
inadvertently introduced into a recipient microorganism when 
requirements that the genetic material be limited in size and well-
characterized are followed. Should any of the necessary sequences not 
be introduced, or not be expressed appropriately by the recipient, a 
toxin of multigenic origin would not be produced. EPA, thus, sees no 
reason why a manufacturer who wishes to modify a microorganism listed 
in proposed Sec. 725.420 with a single or a few sequences involved in 
metabolism of a multigenic toxin should not be allowed to do so. 
Introduction of a single or a few such sequences into a candidate 
microorganism should not result in production of a multigenic toxin and 
thus would not present significant risk.
    Similarly, other properties that might present risk concerns result 
from the interactive expression of a large number of genes. For 
example, pathogenic behavior is the result of a large number of genes 
being appropriately expressed. Because of the complex nature of 
behaviors such as pathogenicity, the probability is low that an insert 
consisting of well-characterized, limited in size genetic material 
could transform the microorganisms listed at proposed Sec. 725.420 into 
microorganisms which display pathogenic behavior. For this reason, with 
the exception of certain toxins which are listed because of their 
potency, EPA is not listing at proposed Sec. 725.421(d) sequences that 
are one of a series of sequences needed in combination in order for a 
microorganism to display a complex behavior such as pathogenicity. If 
commenters believe they can identify sequences which present risk 
concerns which should be addressed and listed at proposed 
Sec. 725.421(d), EPA requests they inform the Agency of these 
sequences.
    (iv) Poorly mobilizable. The requirement, at proposed 
Sec. 725.421(c), that the introduced genetic material be poorly 
mobilizable reduces potential for transfer of introduced genetic 
sequences to other microorganisms in the environment. Such transfers 
would occur through the interaction of the introduced microorganism 
with indigenous microorganisms through conjugation, transduction, or 
transformation. Through such transfers, the introduced genetic material 
could be transferred to and propagated within different populations of 
microorganisms, including microorganisms which may never previously 
have been exposed to this genetic material. It is not possible to 
predict how the behavior of these potential recipient microorganisms 
will be affected after uptake and expression of the genetic material.
    Since EPA is not limiting the type of organism that can serve as 
the source for the introduced genetic material, some limitation is 
placed on the ability of the introduced genetic material to be 
transferred. This limitation mitigates risk by significantly reducing 
the probability that the introduced genetic material would be 
transferred to and expressed by other microorganisms.
    The transfer frequency of 10-8 was selected as defining 
``poorly mobilizable'' for four reasons. First, it represents the lower 
end of the range of transfer frequencies observed in nature. Transfer 
of plasmids, for example, commonly occurs through conjugation between 
bacteria at rates ranging from no detectable transfer (typically less 
than 10-8 transfer events per donor) to 10-2 transfer events 
per donor in soil, water and sewage (Ref. 13). A similar range of 
transfer frequencies has been associated with transduction of 
chromosomal and plasmid DNA in soil and aquatic microcosms (Refs. 14, 
15, and 16). Also, a limited number of studies on natural 
transformation have documented a range of transformation events from 
0.3 x 10-8 to 1 x 10-8 transformants per recipient (Ref. 17). 
Second, studies of certain genetic traits (e.g., amino acid auxotrophy, 
resistance to antibiotics) suggest the spontaneous rate of mutation to 
be within the range of 10-5 to 10-8 per cell generation 
(Refs. 18 and 19). A frequency of 10-8 appears to represent, 
therefore, a baseline frequency at which change occurs in genetic 
material. Third, this frequency sets the technical limit for 
measurability. Below the rate of spontaneous mutation, it becomes 
difficult to distinguish gene transfer from mutation. Fourth, the 
10-8 criterion should not be difficult to meet, and, in fact, is a 
standard employed in the NIH Guidelines.
    The 10-8 frequency is attainable given current techniques. 
Plasmids with transfer rates of 10-8 exist or are easily 
constructed. In bacteria this low rate is readily engineered through 
the inactivation of the transfer functions of mobile genetic elements, 
or the inactivation/removal of pilus formation functions of plasmids 
(Ref. 20). Some of the plasmids most commonly employed as vectors in 
genetic engineering (e.g., pBR325 and pBR322) have mobilization/
transfer frequencies of 10-8 or less. The plasmid pBR322 has been 
used as a vector to construct several microorganisms reviewed by EPA 
under the 1986 Policy Statement.
    The criteria set for ``poorly mobilizable'' for transduction and 
transformation should not prevent most microorganisms from meeting the 
exemption criteria, since the majority of transfer frequencies reported 
for transduction and natural transformation are less than 10-8. 
Higher frequencies are likely only if the introduced genetic material 
has been altered or selected to enhance frequency.
    Fungal gene transfer has also been considered in development of the 
poorly mobilizable criterion. Although mobile genetic elements such as 
transposons, plasmids, and double stranded RNA exist in fungi and can 
be readily transferred, this transfer usually is only possible between 
members of the same species during anastomosis, a process specific to 
fungi. Since anastomosis only occurs between members of the same 
species, the introduced genetic material would not be transferred to 
distantly related fungi as may occur with bacteria.
    Based on suggestions made at the July 22, 1991 BSAC Subcommittee 
meeting, EPA proposes the following definition for ``poorly 
mobilizable'': ``The ability of the introduced genetic material to be 
transferred and mobilized is inactivated, with a resulting frequency of 
transfer of less than 10-8 transfer events per recipient.'' For 
microorganisms with introduced genetic material associated with 
conjugative plasmids or conjugative transposons, this criterion can be 
met by inactivation of transfer or mobilization functions which reduce 
transfer frequency. In instances where introduced genetic material is 
located on the chromosome, steps can be taken to insure a low transfer 
frequency by transduction and transformation by reducing opportunities 
for illegitimate recombination. EPA requests comment on the 
appropriateness of its definition of poorly mobilizable and whether 
there are alternative or additional methods for demonstrating that 
introduced genetic material is poorly mobilizable that should be 
included in the definition.
    (v) Effect of introduced genetic material criteria. The 
requirements placed on the introduced genetic material, in concert with 
the level of safety associated with the recipient microorganisms, 
ensure that the resulting microorganisms present low or negligible 
risk. The probability is low that the insertion of genetic material 
meeting EPA's criteria into such microorganisms will change their 
behavior so that they would acquire the potential for causing adverse 
effects. Risks would be mitigated by the four criteria placed on the 
introduced genetic material, the relative safety of the microorganisms 
listed at proposed Sec. 725.420, and the inactivation criteria 
specified for the Tier I exemption. In the case of Tier II exemption, 
risks would be mitigated in light of the four criteria placed on 
introduced genetic material, the relative safety of the microorganisms 
listed at proposed Sec. 725.420, and EPA's review of the conditions 
selected.
    c. Standards for minimizing the number of microorganisms emitted 
from the facility. The standards prescribed for Tier I exemption 
require that the structure(s) be designed and operated to contain the 
microorganism, that access to the structure be limited to essential 
personnel, that inactivation procedures shown to be effective in 
reducing the number of viable microorganisms in liquid and solid wastes 
be followed prior to disposal of the wastes, that features to reduce 
microbial concentrations in aerosols and exhaust gases released from 
the structure be in place, and that general worker hygiene and 
protection practices be followed.
    (i) Definition of structure. EPA considers the term ``structure'' 
to refer to the building or vessel which effectively surrounds and 
encloses the microorganism. Vessels may have a variety of forms, e.g., 
cubic, ovoid, cylindrical, or spherical, and may be the fermentation 
vessel proper or part of the downstream product separation and 
purification line. All would perform the function of enclosing the 
microorganism. In general, the material used in the construction of 
such structure(s) would be impermeable, resistant to corrosion and easy 
to clean/sterilize. Seams, joints, fittings, associated process piping, 
fasteners, and other similar elements would be sealed.
    (ii) Standards to minimize microbial release. EPA is proposing, for 
several reasons, a somewhat cautious approach in prescribing standards 
for minimizing the number of microorganisms emitted through the 
disposal of waste and the venting of gases. First, a wide range of 
behaviors can be displayed by microorganisms modified consistent with 
EPA's standards for the introduced genetic material. Second, EPA will 
not conduct any review whatsoever for Tier I exemptions. EPA believes 
the requirement to minimize emissions will provide a measure of risk 
reduction necessary for making a finding of no unreasonable risk. Taken 
together, EPA's standards ensure that the number of microorganisms 
emitted from the structure is minimized.
    EPA's proposed standards for minimizing emission specify that 
liquid and solid waste containing the microorganisms be treated to give 
a validated decrease in viable microbial populations so that at least 
99.9999 percent of the organisms resulting from the fermentation will 
be killed. During normal fermentation processes, bacteria generally 
reach a level of 1010 to 1011 colony forming units per 
milliliter (Ref. 21). A simple calculation assuming no dilution of the 
fermentor broth and a minimum inactivation efficiency of 99.9999 
percent (or a 6 log reduction) results in an estimate of the 
concentration of viable organisms released from the facility of at most 
approximately 105 bacteria per milliliter. This number is likely 
to be lower, since the required reduction is the minimum validated 
inactivation and the actual kill is likely to be greater.
    Fungi have greater biomass per colony forming unit and therefore 
are incapable of reaching the high numbers that bacteria in 
fermentation vats achieve. During the fermentation process, fungal 
populations frequently reach population densities of 106 to 
107 microorganisms per milliliter (Ref. 21). The proposed level of 
inactivation would result in almost all fungi from the fermentation 
process being rendered nonviable. Here too, the actual reduction in 
number is likely to be greater that the minimum required by EPA.
    Since the bacteria used in fermentation processes are usually 
debilitated, either intentionally or through acclimation to industrial 
fermentation, the small fraction of microorganisms remaining viable 
after inactivation treatments will likely have a reduced ability to 
survive during disposal or in the environment. This is because 
microorganisms repeatedly cultured in specific growth conditions become 
adapted to those conditions and often lose the ability to survive in 
different conditions. This is particularly true when microorganisms are 
used in industrial fermentations wherein most, if not all, of the 
microorganism's nutritional and other needs are met to ensure rapid 
growth and good product yield. Moreover, industrial companies, in an 
attempt to keep their proprietary microorganisms from competitors and 
to reduce the microbial numbers to those permitted by local sanitation 
authorities, modify the microorganisms to increase the ability of their 
microorganisms to survive and perform their assigned tasks in the 
fermentor but decrease their ability to survive in the environment 
external to the fermentor.
    When treated wastes are placed in the sanitary sewage line during 
disposal, factors such as changes in pH, temperature, ionic balance, 
and dilution adversely affect any microorganisms remaining viable 
subsequent to inactivation treatment. Similarly, when such wastes are 
left in the form of cakes for several hours at room temperature, the 
lack of nutrients and sufficient suitable electron acceptors (oxygen 
for aerobes, other substances such as an organic compound or sulfur for 
anaerobes) further reduces viability. Based on these considerations, 
EPA believes that under its proposed standards, few viable 
microorganisms will be emitted from the facility through the route of 
liquid and solid wastes.
    EPA requirements also address microorganisms in the exhaust from 
the fermentor and along the production line. To address exhaust from 
fermentors, EPA is proposing that the number of microorganisms in 
fermentor gases be reduced by at least two logs prior to the gases 
being exhausted from the fermentor. EPA selected this number based on 
an estimate of the numbers of microorganisms likely to be in the 
exhaust from an uncontrolled fermentor and common industry practice. 
Several studies cited by Battelle (Ref. 22) suggest that a typical 
viable microorganism load in uncontrolled fermentor exhaust is about 5 
x 104 organisms per cubic foot. A reduction of two logs would 
reduce the number to approximately 5 x 102 microorganisms per 
cubic foot. The actual number is likely to be lower, since the required 
reduction is a minimum and the number removed may be greater.
    The number of microorganisms that remain viable subsequent to being 
exhausted from the fermentor is likely to be lower still. First, it is 
generally not common industry practice to run fermentors in an 
uncontrolled fashion. Second, microorganisms in fermentor exhausts 
would be within aerosols. Aerosolization is, in general, very stressful 
for microorganisms, because of the physical pressures associated with 
aerosol formation and the high probability of dehydration (Refs. 22 and 
23). Moreover, microorganisms that are physiologically acclimated to 
the growth conditions within the fermentor are likely to be compromised 
in their ability to survive aerosolization. EPA anticipates, therefore, 
that few microorganisms will survive the stresses of aerosolization 
associated with being exhausted in a gas from the fermentor. The 
provision requiring reduction of microorganisms in fermentor exhaust 
gases contributes to minimizing the number of viable microorganisms 
emitted from the facility.
    EPA requests comment on whether its standards for minimizing 
releases of microorganisms from facilities are appropriate for this 
exemption. EPA is particularly interested in whether commenters can 
suggest reasonable alternative methods for reducing releases from 
facilities and provide the rationale for these alternatives.
    EPA is also proposing that the requirements specify that other 
systems be in place to control dissemination of microorganisms by other 
routes. This would include programs to control pests such as insects or 
rats, since these might serve as vectors for carrying microorganisms 
out of the fermentation facilities.
    (iii) Worker protection. The requirement to minimize microbial 
emissions, in conjunction with the requirement for general worker 
safety and hygiene procedures, also affords a measure of protection for 
workers. Potential effects on workers that exist with microorganisms in 
general (e.g., allergenicity) will be present with the microorganisms 
qualifying for this exemption. As with other substances that humans may 
react to (e.g., pollen, chemicals, dust), the type and degree of 
allergenic responses is determined by the biology of the exposed 
individual. It is unlikely that a microorganism modified in keeping 
with EPA's specifications for the introduced genetic material would 
induce a heightened response. The general worker hygiene procedures 
specified by EPA should protect most individuals from the allergenic 
responses associated with microorganisms exhausted from fermentors and/
or other substances emitted along the production line. The EPA 
requirement that entry be limited to essential personnel also addresses 
this consideration by reducing to a minimum the number of individuals 
exposed.
    (iv) Guidance for Tier II. EPA is not specifying standards for 
minimizing the number of microorganisms emitted from the facility for 
microorganisms qualifying for Tier II exemption. Rather, the Agency 
requests that submitters utilize as guidance the standards set forth 
for Tier I procedures. The procedures proposed by the submitter in a 
Tier II exemption request will be quickly reviewed by the Agency (45 
days). EPA will have the opportunity to evaluate whether the procedures 
the submitter intends to implement for reducing the number of organisms 
emitted from the facility are appropriate for that microorganism.
    d. Benefits of the tiered exemption. Substantial benefits are 
associated with this proposed exemption. The recipient microorganisms 
are already widely employed in general commercial uses subject to TSCA 
reporting. These include microorganisms used to produce enzymes for 
detergent use or biomass conversion, and production of specific 
compounds such as plant or microbial growth promoting factors.
    The Agency believes this exemption will result in resource savings 
both to EPA and industry without compromising the level of risk 
management afforded by the 90-day MCAN review. The microorganisms named 
as recipients for the tiered exemption have been assessed for risk, 
criteria limiting the potential for transfer of and expression of toxin 
sequences have been provided, and the conditions of use are specified 
in the exemption (Tier I) or will be reviewed by EPA (Tier II). EPA 
requirements for minimizing numbers of viable microorganisms emitted 
are within standard operating procedures for the industry, and both the 
procedures and the structures specified in the exemption are the type 
industry uses to protect their products from contamination.
    The exemption will result in reduced reporting costs and a decrease 
in delay associated with reporting requirements. The savings in Agency 
resources can be directed to reviewing activities and microorganisms 
which present greater uncertainty.
    This exemption should facilitate development and manufacturing of 
new products and the accumulation of useful information. When balanced 
by the potential resource savings and many industrial benefits of these 
microorganisms, the Agency finds the potential benefits of exempting 
uses of these microorganisms under the specific criteria will not 
present unreasonable risk.
    EPA is considering designating other microorganisms as eligible for 
this exemption, dependent upon risk assessments for these 
microorganisms indicating that they present no unreasonable risk under 
the conditions of use. A list of microorganisms EPA believes are used 
by industry for TSCA uses appears in a support document in the docket 
for this rulemaking. EPA plans to evaluate many of these to determine 
whether they qualify as recipient microorganisms eligible for this 
exemption. The goal of the evaluation is to ensure that the 
microorganisms would present no unreasonable risk when used under the 
conditions of this exemption. Persons possessing information 
demonstrating no unreasonable risk and thus supporting eligibility for 
the tiered exemption for these microorganisms or other microorganisms 
are encouraged to submit such information to EPA to facilitate this 
process. As noted previously, this information could be submitted using 
the procedures at proposed Sec. 725.67.

IV. Other Issues

A. Microorganisms Covered in This Rulemaking

    1. Microorganisms included. In this proposed rule, EPA, on the 
advice of its BSAC, is including in its definition of ``microorganism'' 
those organisms classified in the kingdoms Monera (or Procaryotae), 
Protista, and Fungi, the Chlorophyta and the Rhodophyta of the Plantae, 
and viruses and virus-like particles. This definition, which uses the 
five kingdom classification system of Whittacker (Ref. 24), includes, 
but is not limited to bacteria, protozoa, fungi, mycoplasmas, 
mycoplasma-like organisms, spiroplasmas, microphytoplanktons, and green 
and red algae. Viruses and virus-like particles (e.g viroids, 
satellites, virusoids) are also considered to be microorganisms by EPA, 
even though they are classified in a unique classification system 
described by Francki, et al. (Ref. 25). Should new categories of 
organisms within the Monera, Protista, Fungi, and the Chlorophyta and 
the Rhodophyta of the Plantae be identified, these also would be 
considered microorganisms under this proposed rule. EPA requests 
comment on its approach to the definition of microorganisms. EPA is 
particularly interested in comment regarding the appropriateness of 
including organisms from the Chlorophyta and the Rhodophyta of the 
Plantae in its microorganism definition.
    The organisms belonging to the Monera, Protista and Fungi are 
primarily unicellular. Members of the Chlorophyta and the Rhodophyta 
are also primarily unicellular. As members of the Thallophyta, they 
show little if any tissue differentiation (the entire plant is known as 
a thallus), the reproductive structures are often unicellular and lack 
a protective wall or jacket of sterile cells, and the zygotes do not 
form embryos within a female reproductive organ. The organisms of the 
Monera, Protista, Fungi, Chlorophyta, and Rhodophyta may be prokaryotes 
or eukaryotes, and may or may not possess cell walls.
    Each type of microorganism can be significantly different, one from 
another. Some measure of the differences between them can be seen in 
the fact that the descriptor, ``microorganism'', spans four of the five 
kingdoms into which all organisms are classified. These differences 
present several challenges in constructing a rule.
    2. Inclusion of viruses and virus-like particles. One important 
consideration under TSCA revolves around the approach to viruses and 
virus-like particles. Viruses are included by EPA in the designation 
``microorganisms.'' These entities, which are among the smallest of 
microorganisms, differ from other microorganisms in several ways. 
First, they are non-cellular entities, lacking a delineating cell 
membrane and the metabolic machinery for the basic cellular function of 
energy generation. Second, they contain only one type of genetic 
informational molecule, either RNA (ribonucleic acid) or DNA 
(deoxyribonucleic acid). Third, viruses are obligate intracellular 
inhabitants. They cannot reproduce independently outside of a host 
cell. For this reason, viruses have historically been identified 
according to the host they infect, i.e., plant viruses reproduce in 
plant cells, animal viruses in animal cells, and bacterial viruses in 
bacterial cells. There are also viruses of fungi, algae, and protozoa. 
More recently a unique classification system has been developed based 
on the genome structure and expression, as well as on structural 
features of the virus particles (Ref. 25). Because their reproduction 
within cells can result in disruption of the host cell, viruses are 
generally considered to be pathogens. Viroids are virus-like particles 
which are also pathogens. These entities are implicated in plant 
diseases such as potato spindle tuber disease.
    When the BSAC Subcommittee met on July 22, 1991, they considered 
EPA's approach to microorganisms under TSCA. They raised several issues 
with regard to viruses and virus-like particles. They noted that 
viruses are by definition pathogens. As viruses in general have smaller 
genomes than other microorganisms and a greater percentage of the 
genome is related to pathogenicity, a change in the viral genome is 
more likely to affect pathogenicity than a change in the genome of 
microorganisms such as bacteria and fungi. Even when a change occurs 
solely within a single genome, viruses and virus-like particles may 
warrant a more cautious approach than other microorganisms. Finally, 
plant and animal viruses are known to shift host range under in vitro 
tissue culture conditions, other unique conditions, or in non-
traditional hosts, and this, in and of itself, is an important risk 
consideration.
    Thus, viruses and virus-like particles, because of their unique 
characteristics, present different issues than other microorganisms. 
This is particularly true of the viruses that attack macroorganisms 
(humans, animals, and plants); and the use of these viruses probably 
warrants scrutiny regardless of whether the virus is new or existing.
    Viruses that infect other microorganisms (e.g., the viruses of 
protozoa, fungi, and bacteria), may present a somewhat different risk 
picture from those that infect macroorganisms. Although it appears 
theoretically possible for a virus of a microorganism (also termed a 
phage) to permanently eliminate its host microorganism from a habitat, 
studies done to date do not provide strong evidence that this occurs 
(Ref. 24), possibly because microorganisms are capable of rapidly 
developing resistance to phage infection. Phage infections appear 
rather to result in a temporary fluctuation rather than a permanent 
change in the numbers of a microorganism in a specific habitat. 
Moreover, redundancy in function found in natural microbial communities 
(i.e., many species are capable of performing the same ecological 
function (Ref. 5)) may cushion the effects of these population fluxes.
    To address viruses for this rulemaking, EPA has distinguished 
between those that infect microorganisms and those that infect 
macroorganisms. Phages will be considered MGEs and the MGE guidance 
discussed in Unit I.C. of this preamble will apply to them. Therefore, 
a phage which has been modified to contain genetic material from a 
second phage whose host microorganism is in a different genus than the 
modified phage would be considered a ``new'' microorganism subject to 
TSCA section 5 reporting. Similarly, a phage modified to contain 
genetic material from an organism classified in a different genus than 
the genus from which the modified (recipient) phage was isolated would 
be considered intergeneric. Under this interpretation, a phage which 
has been modified to contain genetic material from a virus of a 
macroorganism would also be considered a ``new'' microorganism.
    With regard to viruses of macroorganisms, EPA believes that certain 
viruses of macroorganisms would be subject to TSCA jurisdiction if they 
were employed in TSCA uses. As discussed in Unit I.C. of this preamble, 
certain product uses are excluded from coverage under TSCA, the most 
notable for viruses being the exclusions for pesticides (but not 
pesticide intermediates) which are covered under FIFRA and for food, 
drugs, cosmetics, and their intermediates, which are covered by FFDCA. 
While other uses could potentially be subject to TSCA, EPA has not at 
this time been able to identify viruses of macroorganisms in uses that 
might be subject to TSCA. EPA requests comments on whether there are 
known uses of viruses of macroorganisms that would be subject to TSCA 
and whether an intergeneric approach such as that used for phages would 
be appropriate for the viruses of macroorganisms. Comment is also 
requested on whether EPA's approach for oversight of phages under TSCA 
section 5 is appropriate.

B. Listing Microorganisms on the Inventory

    This Unit describes how EPA proposes to explicitly list 
microorganisms on the TSCA Inventory after MCAN review and the 
rationale for the proposed listing.
    1. The components of explicit listing. EPA proposes to identify 
microorganisms on the Inventory using a taxonomic designation and a 
consistent set of supplemental information on phenotypic and genotypic 
traits necessary to identify the microorganism as precisely as 
possible. EPA expects that this information would be a portion of the 
information included in MCAN submissions.
    a. Taxonomic designation. The taxonomic designations to the strain 
level, as appropriate, would be provided for the recipient 
microorganism and the donor(s) of the introduced genetic material. 
Taxonomic designations may be those assigned by individual submitters 
or by a culture collection. The designations would be substantiated by 
a letter from a culture collection verifying the designation, by 
literature references, or by the results of tests conducted for the 
purpose of taxonomic classification. Upon request, the data supporting 
the taxonomic designation should be provided to EPA. Where possible, 
the genetic history of the recipient microorganism should be documented 
back to the isolate from which it was derived.
    b. Supplemental information. Many taxonomic designations at the 
species level define phenotypically and genotypically diverse groups of 
microorganisms. Therefore, supplemental information will be used to 
identify as precisely as possible a specific microorganism on the 
Inventory. Information on phenotypic and genotypic traits is necessary 
only to the extent that it assists in the specific identification of 
the reported microorganism.
    (i) Phenotypic traits. This information concerns the 
characteristics that reflect the interaction of a microorganism's 
genotype and the environment in which it is intended to be used. For 
example, information on intentionally added biochemical and 
physiological traits is pertinent, since these traits may affect the 
behavior and fate of a microorganism in the environment. Where 
possible, submitters should prioritize phenotypic traits in order of 
those likely to significantly change the microorganism's behavior and 
thus its potential risk. Such important phenotypic changes may include 
a change from asporogeny to spore-forming, an increase in the amount of 
a specific product for which the microorganism is being used as an 
intermediate, or the activation of a previously inactive enzyme that is 
known to have negative human health or ecological effects.
    (ii) Genotypic traits. This information concerns the distinguishing 
genotypic characteristics of a microorganism, including the identity of 
the genetic material that is introduced into the recipient 
microorganism and the methods used to construct the reported 
microorganism. For example, information on the vector construct, 
cellular location, and number of copies of the introduced genetic 
material is pertinent, since the vector may add genetic material and 
traits, and the microorganism's phenotypic traits may be affected by 
the number of copies and location of the introduced genetic material.
    c. Deposit in a culture collection. Because microorganisms are 
complex substances and because of the nature of the differences that 
will be used to distinguish between similar organisms (isolates), EPA 
is considering requiring that microorganisms listed on the Inventory be 
deposited in a recognized culture collection. Deposited microorganisms 
could serve as references for determining whether a related, unreported 
microorganism, or a subsequently modified, inventoried microorganism is 
the same as one already listed on the Inventory. Comments on this 
proposal and alternative suggestions of how to distinguish among 
closely related microorganisms are requested.
    2. Inventory status of similar and subsequently modified 
microorganisms. Since publication of the 1986 Policy Statement, EPA has 
reviewed several intergeneric microorganism PMNs for general commercial 
use. As discussed previously, the Agency has received an NOC for most 
of these microorganisms, and these are listed on the TSCA Inventory. 
The Agency recognizes that subsequent to listing a microorganism on the 
Inventory, original submitters may make modifications to the genetic 
material of the inventoried microorganism or companies other than the 
original submitter may construct microorganisms which may be equivalent 
to inventoried microorganisms. Questions would arise as to whether the 
modified microorganism is equivalent to the microorganism listed on the 
Inventory. At this time, EPA has concluded that no a priori guidance 
can be given for determining whether a similar strain will be 
equivalent to one listed on the Inventory. Manufacturers, producers, or 
importers should consult with EPA concerning the status of their 
microorganisms, as discussed in Unit II.B.1. of this preamble.
    In making its decision on an individual microorganism, EPA will 
consider the phenotype of the inventoried microorganism and assess how 
the subsequent modifications will affect that phenotype. For example, 
EPA believes that a MCAN may not be required when an inventoried 
microorganism has undergone certain subsequent modifications of genetic 
material where these modifications would not be likely to significantly 
change the microorganism's behavior. The BSAC Subcommittee which met on 
July 22, 1991, suggested that EPA continue to make these decisions on a 
case-by-case basis, at least until EPA gains more experience. Although 
EPA will make its decisions on a case-by-case basis, microorganisms 
that may be judged by EPA to be equivalent to inventoried 
microorganisms include those that have experienced deletions, 
rearrangements, amplifications, point mutations, and/or plasmid loss 
within a single genome, either spontaneously or through use of chemical 
or physical mutagens. The Agency recognizes that deletions, 
rearrangements, amplifications, point mutations, and plasmid loss could 
occur spontaneously in any microorganism maintained in pure culture, in 
response to stresses such as freezing or thawing, or as a result of 
mistakes made during the microorganism's replication of its genetic 
material.
    EPA recommends that potential submitters consult the Agency for 
clarification of their reporting obligations whenever additional 
changes are made to inventoried microorganisms. The Agency has reviewed 
several bona fide submissions and has determined on a case-by-case 
basis that the microorganisms described were equivalent to previous PMN 
submissions. In one case, the microorganism which was the subject of 
the bona fide submission was derived from the same strain as the 
inventoried microorganism using similar methods, and intrageneric 
material encoding the same enzyme function was introduced. Although a 
small number of base pairs in the intrageneric material had been 
genetically altered, no new trait was introduced into the bona fide 
microorganism compared to the inventoried microorganism. In a separate 
case, the bona fide microorganism contained genetically modified 
intrageneric material encoding the same function introduced into the 
inventoried microorganism as well as a small fragment of non-coding, 
non-regulatory intergeneric genetic material that had been derived from 
the same source as that introduced into the inventoried microorganism. 
Although a small number of base pairs had been altered in this 
intergeneric material, no new trait was present in the bona fide 
microorganism compared to the inventoried microorganism.
    3. Identification of microorganisms currently listed on the 
Inventory. EPA wishes to provide manufacturers and processors who are 
using microorganisms which were listed on the Inventory prior to the 
1986 Policy Statement the opportunity to provide information for a 
specific, explicit listing, if necessary. In 1978, when EPA compiled 
its initial TSCA Inventory, 192 microorganisms were reported. These 
microorganisms are currently described on the Inventory by taxonomic 
designations only, without any supplemental information describing how 
they were made. They are listed in the 1985 Edition, Volume V, of the 
TSCA Inventory. The list of microorganisms is included in the docket 
for this rulemaking. The list may be obtained upon request at the 
address included in the FOR FURTHER INFORMATION CONTACT section of this 
preamble. EPA believes that most, if not all, of the 192 microorganisms 
would not be considered new under this proposed rule, since the 
listings appear to describe microorganisms which are not intergeneric. 
Thus, these microorganisms would be implicitly included on the 
Inventory and may continue to be manufactured for general commercial 
use.
    However, EPA wishes to ensure that all listed microorganisms are 
described in a consistent manner. Accordingly, EPA advises 
manufacturers and importers of any of the 192 listed microorganisms to 
inform EPA of their status under this proposed rule during the public 
comment period. Any manufacturers of microorganisms that would be 
considered new under any final rules will be given the opportunity to 
provide information to EPA to ensure consistent listing of the 
microorganisms on the Inventory. If EPA is not notified about a 
microorganism, the Agency will assume it would be implicitly included 
because it is not intergeneric, and it will be removed from the 
Inventory list as an explicit listing under EPA's TSCA section 8(b) 
authority.
    As discussed previously, EPA has reviewed a number of intergeneric 
microorganism PMNs under the 1986 Policy Statement and has listed the 
microorganisms on the Inventory. These microorganisms will be retained 
on the Inventory if the proposal becomes final. If changes are made 
which require alteration of Inventory listings, EPA will announce them 
in the Federal Register.

C. SNUR Process

    EPA is not proposing any significant new use rules (SNURs) in this 
document. Instead, EPA is proposing, in subpart L of part 725, 
procedures to enable it to issue SNURs in the future. Microorganisms 
subject to SNUR reporting would be listed in proposed subpart M of part 
725. This Unit discusses the SNUR process that EPA is proposing. This 
process is adapted from the process in place for traditional chemicals 
in part 721 with only slight modifications.
    1. SNURs applied to microorganisms. Although EPA is not proposing 
SNURs for any microorganisms in this document, it is conceivable that, 
in the future, certain specific uses of microorganisms may raise 
concerns for human health or the environment. Because the behavior of a 
specific microorganism is influenced by the environment into which it 
is introduced (Refs. 5, 7, 8, and 9), it may be necessary to evaluate 
the risk of some microorganisms when the environment of use is changed. 
For example, EPA was asked whether any uses of ``Ice +'' strains of 
Pseudomonas syringae might be subject to SNUR reporting. At the time, 
the ``Ice +'' microorganism was being used for snowmaking at ski 
resorts. In that situation, EPA decided that terrestrial uses of the 
microorganism for such activities as snowmaking at ski resorts, 
icemaking at ice skating rinks, commercial air conditioning, and spray-
ice construction applications did not pose significantly different 
exposures and therefore would not require SNUR reporting to EPA. 
However, EPA did indicate that because use of the microorganism for 
cloudseeding would present a significantly different exposure scenario 
than the terrestrial uses, EPA might require SNUR reporting prior to 
use of the live microorganism for cloudseeding. In such cases, EPA 
believes it may be appropriate to use SNUR authority to monitor the 
commercial development of these substances so that EPA can be apprised 
of significant increases in exposure potential or significant changes 
in exposure patterns. These significant increases may warrant control 
measures or testing. As noted earlier, the MCAN submission and review 
process will be used for microorganisms subject to SNUR reporting.
    2. Expedited process for issuing SNURs. If EPA finds it necessary 
to issue SNURs for new microorganisms reviewed under the MCAN process, 
EPA will use, when appropriate, expedited procedures based on those 
established in part 721, subpart D. The procedures for issuing 
expedited SNURs for microorganisms are set forth in proposed 
Sec. 725.980. EPA is not soliciting separate public comment on these 
procedures, since they have already been adopted by EPA. This section 
relies on the rationale originally stated in the Federal Register 
notices establishing the expedited SNUR process for other new 
substances under part 721. The SNUR procedures are discussed here and 
included in the regulatory text for completeness, so that the public 
will understand all the regulatory provisions potentially applicable to 
microorganisms.
    A limited amount of toxicity data is typically submitted with 
premanufacture notifications (PMNs) for chemical substances. Thus, EPA 
often bases its reviews on structure-activity relationships (SARs). 
MCANs are expected to present similar problems in data gaps, since 
current knowledge of microbial ecology is limited, and microorganisms 
subject to TSCA are expected to be used in an ever-expanding variety of 
applications and thus a multitude of different exposures. Should the 
Agency determine it does not possess sufficient information to make a 
risk judgement, EPA could find under TSCA section 5(e) that it had 
insufficient information to determine whether the new microorganism 
presents an unreasonable risk of injury to health or the environment. 
In most such cases, EPA believes that it is appropriate to negotiate a 
consent order under section 5(e) with the notice submitter to control 
human exposure and/or environmental releases until test data or other 
information sufficient to assess adequately the potential hazard become 
available. Current experience indicates that section 5(e) consent 
orders for traditional chemicals have specified a variety of control 
measures. For microorganisms, EPA may place restrictions on site 
location or size, production volume or method of application, field or 
laboratory containment procedures, routine or emergency mitigation 
procedures, or testing procedures.
    Section 5(e) orders are binding on the original notice submitter 
but do not apply to other manufacturers of the same microorganism. 
Without additional regulation, other persons can manufacture, import, 
or process the microorganism without EPA review and without the 
restrictions imposed on the original MCAN submitter by the section 5(e) 
order. To limit all manufacturers equally, EPA imposes SNURs.
    Currently, EPA uses its SNUR authority to extend limitations in 
section 5(e) orders to other manufacturers, importers, and processors 
of chemical substances. This ensures that the original submitter and 
subsequent manufacturers, importers, and processors are treated in an 
equivalent manner. SNURs are framed so that noncompliance with the 
control measures or other restrictions is defined as a ``significant 
new use.'' Thus, other manufacturers, importers, and processors of the 
substances must either observe the SNUR restrictions or submit a notice 
to EPA at least 90 days before initiating activities that deviate from 
these restrictions. After receiving and reviewing such a notice, EPA 
would have the option of either permitting the new use or acting under 
section 5(e) or (f) to regulate the new submitter's activities. EPA 
intends to use this same process for microorganisms. In addition to 
assuring that all manufacturers, importers, and processors are subject 
to similar reporting requirements and restrictions, expedited SNURs 
assure that EPA would have an opportunity to review and evaluate data 
and, when necessary, regulate prospective manufacturers, importers, or 
processors of a listed microorganism before a significant new use of 
that microorganism occurs.

D. Confidential Business Information

    EPA's confidential business information (CBI) policy is designed to 
provide effective public participation by making meaningful information 
available. In developing confidentiality provisions for submissions, 
EPA has balanced the need to provide nonconfidential information to the 
public in a reasonable period of time, to obtain the information it 
needs to respond to FOIA requests, and to allow persons to assert CBI 
claims with the minimum burden. In developing its position for this 
rulemaking, EPA has considered its experience reviewing PMNs for 
traditional chemicals and microorganisms and comments received on its 
February 1989 FR notice. This Unit discusses the requirements proposed 
in subpart C of part 725 and the rationale for EPA's proposal.
    1. Assertion of CBI claims. A person may assert a claim of 
confidentiality for any information submitted to EPA, with certain 
exceptions. However, submitters are encouraged to minimize the amount 
of CBI in biotechnology submissions, so that the public may participate 
as fully as possible in the review process. All CBI claims must be 
asserted at the time of submission of the information.
    2. Generic information. Submitters who claim microorganism identity 
and/or use as CBI also must provide generic information for release to 
the public. By requiring generic identity and use information, EPA 
would meet its obligation to provide the public with important 
information related to the potential risks of new microorganisms 
without revealing CBI. EPA needs this information to prepare Federal 
Register notices to announce EPA's receipt of submissions or EPA's 
decisions regarding exemption requests.
    The generic designations must reveal the identity and use of the 
microorganism to the maximum extent possible without revealing 
proprietary information. Submitters are encouraged to review EPA's 
``Guidelines for the Preparation of Generic Descriptions of 
Confidential Microorganism Identity and Use'' and consult with EPA 
regarding appropriate generic information prior to submitting a notice. 
The guidelines are available from EPA's Environmental Assistance 
Division (see FOR FURTHER INFORMATION CONTACT Unit). Microorganism 
identity must be specific enough to allow clear interpretation of any 
accompanying health and safety data. When the location of the release 
site is claimed as CBI, a generic description for use must include 
information regarding the type of environment into which the 
microorganism will be released.
    3. Identity in health and safety studies. TSCA section 14(b) states 
that EPA is not prohibited from disclosing health and safety studies of 
substances for which TSCA section 5 notification is required, unless 
disclosure reveals confidential information on process or mixture. 
Historically, the Agency has considered specific chemical identity to 
be part of a health and safety study, even when it does not appear in 
the study. However, during the development of the PMN rule, industry 
expressed substantial concern about the harm of disclosing confidential 
chemical identities. At that time EPA explored ways of limiting the 
commercial harm of such disclosure while still meeting the requirements 
of TSCA section 14(b) and providing the public with adequate 
information about health and safety studies. The CBI requirements in 
the final PMN rule reflected EPA's desire to balance these needs (48 FR 
21722, May 13, 1983).
    EPA has determined that the regulations developed to address 
chemical identity in health and safety studies can also be applied to 
microorganism identity. In this regard, if any health and safety 
information has been submitted for the microorganism in question, the 
specific microorganism identity will be held confidential only if 
disclosure would reveal confidential process or mixture information or 
if the specific microorganism identity is not necessary to interpret 
any of the information.
    Under this approach, companies that claim specific microorganism 
identity confidential in their submissions and wish to argue that 
knowledge of the specific identity is not necessary to interpret their 
health and safety information are encouraged to choose generic names 
which are sufficiently specific to allow interpretation of such 
information. Sufficiently specific generic names will tend to support 
arguments that disclosure of the specific microorganism identity is not 
necessary to understand the health and safety information.
    4. Current policy for substantiation of CBI claims. EPA currently 
requires submitters of all PMNs for new microorganisms to be released 
to the environment to substantiate confidentiality claims at the time 
of submission. This includes PMNs for environmental releases of new 
microorganisms for R&D as well as for general commercial use, but it 
does not require upfront substantiation of CBI claims in PMNs for 
closed system uses of new microorganisms. This policy will continue in 
effect, until a final rule is promulgated for microorganisms. Like the 
chemicals program, EPA requires that CBI claims in NOCs for 
microorganisms be reasserted and resubstantiated when the NOC is 
submitted.
    5. Proposed changes for substantiation of CBI claims--a. 
Submissions for general commercial uses of microorganisms. To balance 
the competing needs of opening the review of submissions for 
microorganisms to public scrutiny and participation while protecting 
legitimate CBI claims, EPA proposes to require upfront substantiation 
of CBI claims in all submissions for general commercial uses of 
microorganisms. EPA will not distinguish between closed system uses and 
other uses of microorganisms. Anyone submitting a MCAN, a TME, or a 
Tier II exemption request will be required to substantiate CBI claims 
at the time of submission. Failure to include substantiation of any CBI 
claims, by submitting written answers to the questions, will render the 
submission incomplete; and it will be returned to the submitter.
    EPA believes that the upfront substantiation requirement for CBI 
claims will impose little burden on submitters of MCANs, TMEs, and Tier 
II exemption requests. Because MCAN, TME, and Tier II exemption request 
submitters are ready to put their products on the market, they should 
be able to justify why it will continue to be necessary to keep certain 
information confidential. In addition, given the shorter review period 
for TMEs and Tier II exemption requests, sufficient information may not 
be made available to the public if upfront substantiation of CBI claims 
is not required.
    b. TERA submission. With respect to upfront substantiation for 
TERAs, EPA is proposing two options and asking for public comments on 
both. In comments in response to the 1989 FR notice, industry groups 
raised the issue of adequate protection for R&D. Pointing out that R&D 
activities involving microorganisms will be facing regulatory burdens 
that are not imposed on chemical R&D, industry groups said that 
additional burdens combined with insufficient CBI protection at the R&D 
stage could reduce incentives to innovate. While submitters are 
particularly concerned about protecting information at the R&D stage, 
the public is most interested in participating in the reviews of the 
first environmental releases of new microorganisms. Public interest 
groups commented that upfront substantiation is essential to allow 
public access to information in time to participate in reviews. Because 
EPA recognizes the importance of the interests of both parties, EPA is 
asking for additional comments on how best to resolve this issue for 
CBI claims in TERAs.
    (i) Option 1: Require upfront substantiation of all CBI claims in 
TERAs. EPA is aware that industry believes that this requirement 
imposes a greater burden on R&D submitters than is necessary. 
Experience gained by continuing to require upfront substantiation of 
CBI claims in submissions for R&D activities will help EPA determine 
whether this requirement improves public access to information. In the 
meantime, EPA specifically requests comment on how the burden to 
submitters could be minimized if upfront substantiation of CBI claims 
in TERAs is promulgated as part of the final rule.
    (ii) Option 2: Do not require upfront substantiation of CBI claims 
in TERAs. The second option is to adopt the current requirements for 
chemical PMNs, that is, require CBI substantiation only after the 
receipt of a FOIA request. EPA is concerned that given the shorter 
review period for TERAs, insufficient information may be made available 
to the public if upfront substantiation of CBI claims is not required. 
For this reason, EPA specifically requests comment on how public access 
to information could be improved if submitters were not required to 
provide upfront substantiation of CBI claims in TERAs.
    c. Substantiation questions. EPA's general procedures for 
processing and reviewing confidentiality claims are published at 40 CFR 
part 2. The basic points that should be covered in CBI substantiation 
are set out at 40 CFR Sec. 2.204(e)(4)(i) through (ix). To ensure that 
substantiation responses are appropriate for submissions involving 
microorganisms, EPA has developed a more specific set of questions 
based on the points in 40 CFR part 2. These questions, which are 
delineated in proposed Sec. 725.94, are designed to reduce the burden 
of substantiation by focussing the inquiry on points relevant to a 
biotechnology product.

E. User Fees

    Section 26(b) of TSCA provides that EPA may by rule establish fees 
for persons required to submit data under section 4 or 5 to defray the 
costs of administering TSCA. EPA must take into account the submitter's 
ability to pay the fee and the cost of reviewing the submitted data. 
EPA is using this authority to collect fees for notices submitted on 
microorganisms.
    EPA regulations already require persons to remit fees to EPA when a 
PMN or SNUN is submitted to the Agency for review (40 CFR Sec. 700.45). 
For MCAN submissions, EPA is proposing to amend part 700 to establish a 
fee of $100 for notifications submitted by small businesses, and $2,500 
for all other businesses. For purposes of this proposed rule, small 
businesses are defined as companies with total annual sales of less 
than $40 million. These proposed fees for MCANs are the same as those 
set for submissions of PMNs for other chemical substances. EPA believes 
that its costs of reviewing MCAN notifications will equal or exceed the 
cost of reviewing PMNs for other chemical substances.
    EPA is not proposing user fees for other submissions under this 
proposed rule, including TERAs and Tier II exemption requests. EPA is 
not reopening the general issues applicable to the adoption of user 
fees for comment in this document, since comments on the subject were 
addressed in a final rule published in the Federal Register of August 
17, 1988 (53 FR 31248).

F. Section 8(e) Reporting Requirements

    Any person who manufactures, imports, processes, or distributes in 
commerce a TSCA-covered microorganism, whether new or existing, and/or 
product(s) therefrom (including a person engaged solely in R&D) is 
reminded about the statutory responsibility to immediately report to 
EPA any information the person obtains which reasonably supports the 
conclusion that such microorganism, or a product therefrom, presents a 
substantial risk of injury to health or the environment, unless the 
person has actual knowledge that EPA has been adequately informed 
already about the information. Guidance regarding the section 8(e) 
reporting requirement is provided in EPA's section 8(e) policy 
statement (``Statement of Interpretation and Enforcement Policy; 
Notification of Substantial Risk'' 43 FR 11110; March 16, 1978) and its 
technical amendment (52 FR 20083; May 29, 1987). Additional information 
regarding TSCA section 8(e) reporting is provided in 56 FR 4128 
(February 1, 1991); 56 FR 19514 (April 26, 1991); 56 FR 28458 (June 20, 
1991); and 56 FR 49478 (September 30, 1991).
    Should EPA receive a section 8(e) substantial risk notice with 
respect to the manufacture, importation, processing or distribution in 
commerce of a microorganism, EPA may proceed to regulate the activity 
causing the risk. If EPA determines, under authority of TSCA section 7, 
that the activity or microorganism, including its parts or products, on 
which a section 8(e) notice was received, is ``imminently hazardous'' 
to health or the environment, EPA may require immediate suspension of 
manufacturing, processing or distribution in commerce of the imminently 
hazardous microorganism. EPA also may require any remediation necessary 
to obtain permanent relief as may be necessary to protect health or the 
environment from the unreasonable risks associated with the 
microorganism. This authority applies to any ``imminently hazardous'' 
microorganism or its parts or products, regardless of whether the 
microorganism is used for R&D or manufactured for general commercial 
use.
    The term ``imminently hazardous chemical substance or mixture'' in 
TSCA section 7 means a chemical substance or mixture which presents an 
imminent and unreasonable risk of serious or widespread injury to 
health or the environment. Such a risk is considered imminent if the 
manufacture, processing, distribution in commerce, use or disposal of 
the substance is likely to result in such injury before a final rule 
can be issued under TSCA section 6.

G. Export Notification and State Preemption

    This Unit discusses two other provisions of TSCA concerning export 
notification and Federal preemption that may be of some concern to the 
public in implementing this proposed rule.
    1. General. Section 12 of TSCA generally provides that the Act does 
not apply to chemical substances produced for export. However, section 
12(b)(2) requires, in pertinent part, that EPA must be notified about 
the export of any substance in U.S. production that is subject to a 
rule, an order, or some other relief granted under section 5. EPA must 
then notify the government of the receiving country. EPA's export 
notification regulations are codified at 40 CFR part 707.
    Section 18(a) provides that TSCA generally does not preempt the 
authority of any State or local government to regulate a chemical 
substance. There are some exceptions, however. In particular, section 
18(b) states that, if EPA issues a rule or order under section 5 
``which is applicable to a chemical substance'' and ``which is designed 
to protect against a risk of injury...associated with such substance'', 
no State or local government may issue or continue in effect any 
requirement designed to protect against the same risk, with certain 
exceptions. The exceptions are that the State or local requirement may 
be identical to the Federal requirement, may be issued under authority 
of another Federal law, or may prohibit use of the substance (other 
than in the manufacture or processing of another chemical substance or 
mixture).
    2. Applicability. EPA interprets the exemption of section 12(a) to 
apply only to those microorganisms manufactured, processed, or 
distributed solely for export. If the microorganism is manufactured, 
processed, or distributed for any use in the United States, it is 
subject to TSCA (see TSCA section 12(a)(1)(A)). Thus, any R&D in the 
U.S. is subject to applicable regulations, as are any other activities 
involving a microorganism that are described in this proposed rule. 
Similarly, any release of microorganisms to the environment prior to 
export will not be considered solely for export and is therefore 
subject to applicable regulations.
    Since the rules proposed in this document are either of general 
applicability and largely procedural, or are exemptions from regulation 
and only establish procedures to screen against potential risk, neither 
section 12(b) export notification nor section 18(b) preemption applies 
at this time.
    Sections 12(b) and 18(b) would apply should EPA decide to take 
regulatory action against a microorganism or class of microorganisms, 
for example, by issuing an order under TSCA section 5(e). In such 
cases, section 12(b) export notification would apply automatically. 
While preemption under section 18(b) would apply by operation of 
statute, in individual cases EPA could issue rules that specifically 
require compliance with applicable State or local requirements.

H. Regulatory Text Overview

    The regulatory text comprises the language which EPA is proposing 
to incorporate into the Code of Federal Regulations (CFR). While the 
preamble to this proposed rule provides the rationale for EPA's 
preferred approach towards the oversight of certain activities 
involving new microorganisms, the regulatory text includes all the 
proposed requirements to which the regulated community would be 
subject.
    The regulatory text amends existing regulations regarding the 
collection of fees from submitters of notices under section 5 of TSCA 
(40 CFR part 700), to reflect the fee structure for the notices and 
applications that have been developed by this proposed rule. Additional 
amendments to parts 720, 721, and 723 consolidate TSCA section 5 review 
of microorganisms into part 725.
    EPA is proposing to establish a new part 725 of Title 40 of the 
CFR. EPA believes that consolidating all requirements and procedures 
applicable to new microorganisms into one part of the CFR is justified 
because of the differences between microorganisms and other chemical 
substances.
    The consolidation will benefit the public by providing greater 
clarity. Part 725 is devoted exclusively to the review of 
microorganisms under section 5 of TSCA and is currently divided into 
eight subparts. Subparts A, B, and C consolidate provisions primarily 
adapted from parts 720 and 721. Subpart A, which includes definitions 
that are applicable throughout part 725, describes general provisions 
and applicability. Subpart B describes administrative procedures that 
are applicable to all submissions under part 725. Subpart C describes 
confidentiality provisions that are applicable to all submissions under 
part 725.
    Subpart D, which combines the general PMN and SNUN requirements 
adapted from parts 720 and 721, describes the reporting requirements 
and review process pertaining to MCANs. Subparts E, F, and G describe 
the reporting requirements and review processes for applications for 
exemptions from full MCAN reporting. Subpart E, which is almost 
entirely new, describes who is eligible to submit a TERA or receive a 
TERA list exemption, and what criteria must be met to receive an 
exemption from EPA review for certain types of R&D activities. Subpart 
F, which is an adaptation of Sec. 720.38, describes the requirements 
for a test marketing exemption for microorganisms. Subpart G, which is 
entirely new, describes what criteria must be met in order to qualify 
for Tier I or Tier II exemptions for certain microorganisms in general 
commercial use. Subpart L, which is adapted from part 721, describes 
additional procedures for reporting significant new uses of 
microorganisms. Although significant new use rules are not being 
proposed at this time, it is intended that subpart M will list 
microorganisms and specific significant new uses when they are 
promulgated.

I. Rulemaking Process and Public Hearings

    EPA is conducting this rulemaking under notice and comment 
rulemaking procedures. Interested persons have the opportunity to 
submit written comments to the address identified under the ADDRESSES 
Unit of this preamble. EPA will carefully consider all such comments.
    EPA is also providing an opportunity for an informal public hearing 
on the proposed rule. This hearing will be held only if EPA receives a 
timely written request for such a hearing.
    As a general matter, EPA is not required to hold a public hearing 
in informal notice and comment rulemaking of this type. However, use of 
section 5(h)(4) modifies the general rulemaking requirements by 
referencing TSCA section 6(c)(2) and (3) rulemaking procedures. Under 
those procedures, EPA must hold an informal public hearing, if 
requested, and, if properly requested and granted by EPA, allow an 
opportunity to present rebuttal submissions and conduct cross-
examinations related to disputed issues of material fact.
    EPA does not anticipate that, even if a hearing is held, there will 
be a need for rebuttal submissions and crossexamination, because the 
section 5(h)(4) portion of this proposed rulemaking is based primarily 
on matters of science policy that do not yield disputed factual issues.

V. Economic Impact and Regulatory Flexibility Analysis

A. Regulatory Impact Analysis

    1. Introduction. EPA has prepared a Regulatory Impact Analysis 
(RIA) assessing the costs, benefits, and associated impacts of 
regulating new microorganisms under TSCA as set forth in the proposed 
rule. Though direct regulatory costs attributable to the proposed rule 
were not estimated to be in excess of $100 million annually, EPA has 
designated the rule as ``significant'' under Executive Order 12866 
because it raises novel policy issues arising out of legal mandates. 
This unit presents a summary of the RIA's key findings and estimates.
    2. Characteristics of the regulated community. Although unable to 
quantify the exact magnitude of activity in biotechnology sectors 
affected by this rulemaking, the Agency believes that activities 
involving microorganisms falling within the scope of the proposed rule 
comprise a modest share of overall activity. EPA estimates that 
approximately 130 firms may be involved in commercial R&D or in general 
commercial use of potentially regulated microorganisms. In terms of 
revenue, the potentially affected universe appears to be divided 
sharply between large and small firms. EPA estimates roughly one-half 
of the companies potentially affected to have annual sales of $40 
million or more, while most of those remaining are estimated to have 
sales under $10 million. For many of these firms, however, revenue 
generated from activities subject to this proposal is believed to 
represent only a small portion of reported sales. EPA also estimates 
that approximately 300 universities could be affected by the 
rulemaking.
    3. Costs to potential submitters. Due to data limitations and the 
uncertainties associated with projecting future product development 
activities in biotechnology application areas subject to the proposed 
rule, EPA's estimates of the costs of compliance associated with this 
rulemaking action have been only partially quantified. In cases where 
the Agency was able to generate quantified estimates of compliance 
costs, information which would have permitted the development of more 
accurate estimates was frequently unavailable. In such cases, the best 
available information was used. Estimates are believed to represent a 
reasonable approximation of actual costs attributable to the rule.
    In assessing the potential cost impact of the proposed rule, EPA 
focussed on two impact years, the first and fifth years following the 
time of proposal (assumed to be 1992 and 1996, for the purposes of 
analysis). This approach was used because of the relative immaturity of 
the biotechnology sectors potentially subject to the proposed rule and 
the difficulty in attempting to forecast long-term technological and 
marketing developments. However, EPA wishes to emphasize that estimated 
costs could be significantly higher in the long-term, owing to industry 
growth.
    Four major cost areas were identified, based on an analysis of the 
requirements of the proposed rule. These areas were costs incurred in 
preparing various types of notification submissions or documentation; 
costs incurred in complying with any post review requirements for 
monitoring or controls that may be imposed by EPA as a result of risk 
concerns and uncertainties; costs incurred in substantiating 
confidential business information (CBI) claims; and one-time costs 
attributable to rule familiarization.
    Incremental costs to industry (industry-wide costs excluding 
requirements under current policy) were estimated to fall between 
$890,000 and $2.2 million in year 1 and between $56,000 and $460,000 in 
year 5. Year 5 costs account for rule familiarization only in the case 
of new firms entering the affected market areas, and therefore are much 
less than year 1 costs, where rule familiarization costs were summed 
over all affected entities.
    Cost impacts on individual products will vary, depending on 
application area. Submitters qualifying for exemptions in connection 
with microorganisms intended for general commercial use will realize 
net savings relative to current reporting requirements. On the other 
hand, submitters reporting R&D activities involving environmental 
release may realize an increase in regulatory burden under the proposed 
rule.
    4. Costs to the Federal government. EPA estimated the potential 
costs to government associated with the proposed rule. These costs 
arise in connection with the Agency's processing of individual 
notification submissions. In estimating government cost impacts, EPA 
included costs estimated to be incurred in reviewing each submission. 
EPA professionals and members of the Biotechnology Science Advisory 
Committee were assumed to be involved in such review. In the event that 
post-review restrictions would be placed on a specific activity, such 
as monitoring during a field test, additional costs attributable to the 
drawing up of regulatory documentation would be incurred.
    Incremental costs to the government were estimated to fall between 
$115,000 and $122,000 in year 1, while a net savings to EPA, estimated 
to fall between $39,000 and $184,000, is expected in year 5. These 
savings arise in connection with the substantial number of full reviews 
that will be avoided if the exemption provisions of the proposed rule 
are promulgated.
    5. Benefits of the proposed rule. EPA's regulation of new 
microorganisms under TSCA provides benefits to society through 
reduction of the potential for adverse impacts on health and the 
environment resulting from the use of such microorganisms. This benefit 
is achieved by screening new microorganisms and, when appropriate, 
imposing controls on microorganism use to protect society from costly 
and possibly irreversible damages.
    For microorganisms in general commercial use, risk reduction 
attributable strictly to the notification requirements of proposed rule 
would be marginal, as these requirements are based on current policy. 
However, the proposed rule enhances and contributes to the overall risk 
reduction potential of the Agency's program under TSCA by providing for 
a more efficient regulatory strategy relative to current policy, 
focussing society's resources on those new microorganisms of greatest 
concern.
    For microorganisms in commercial R&D, a greater proportion of 
overall risk reduction can be attributed to the proposed rule, since 
reporting in connection with field experiments has been voluntary since 
1986. Although the Agency has been receiving voluntary submissions, EPA 
is not certain whether this practice is universal or whether those 
filing voluntarily would continue to do so in the absence of this 
proposed rule.
    Over the long-term, regulation is also likely to encourage 
development of additional information concerning fate and effects of 
new microorganisms, to encourage the development of microorganisms 
which pose low concern for effects on human health and the environment, 
and to encourage public input into decisions concerning the use of new 
microorganisms.
    Benefits may also be realized through the proposed rule's potential 
impact on the pace of product development. A more certain regulatory 
climate could stimulate business activity, as could a more reassured 
public. The proposed rule may also reduce the possibility of continued 
regulatory activity at the State and local level. A national system of 
potentially uncoordinated rulemaking initiatives could lead to market 
distortion and could hamper competition.
    6. Effects of the proposed rule on innovative activity. As a result 
of the proposed rule, members of the regulated community may find 
product development strategies in connection with certain products to 
require reassessment. Since impacts of this nature could influence the 
degree of emphasis a firm places on innovative activity, the potential 
for innovation impacts was investigated.
    Though great uncertainty regarding regulatory costs and the 
potential for a particular product's commercial success make it 
impossible to estimate innovation impacts quantitatively, the effects 
of added regulatory costs and delays on a product's lifetime cash-flow 
was examined. More specifically, a number of plausible product 
development scenarios were modeled incorporating assumptions regarding 
expenditures and returns over the course of a product's useful life 
from research to obsolescence. Regulatory burdens were then factored 
into the models, and profit impacts observed. Impacts realized when 
total regulatory costs were assumed to reach the upper-bound of EPA's 
estimated range could result in severe profit reductions in some cases. 
However, in general, EPA's analysis indicated that impacts should not 
be prohibitive, particularly when incremental costs are considered. 
Factors such as length of delay related to regulatory review, return 
rate, and obsolescence rate all play important roles in determining the 
impact of EPA's program on innovative activity. These factors are 
expected to be highly variable and product-specific.
    7. Impacts on small business. EPA survey data suggest that 42 
percent of companies potentially affected by the proposed rule may be 
small businesses. Though data were not available allowing the Agency to 
employ standard criteria for assessing the magnitude of small business 
impacts, the finding of a substantial portion of the regulated 
community to be small businesses prompted EPA to develop options to 
provide relief to such businesses. The options considered include 
reducing CBI substantiation requirements and the elimination of the 
$100 filing fee.

B. Request for Comment on Economic Issues

    Based on the analysis presented in the RIA, EPA's preliminary 
findings are that this proposed rule should not adversely affect either 
innovation or international competitiveness in biotechnology; to the 
contrary, EPA believes that this proposed rule will provide needed 
regulatory and procedural clarity under TSCA to enable the U.S. 
biotechnology industry to commercialize products while ensuring 
appropriate oversight to protect public health and the environment.
    EPA nevertheless believes that this proposed rule should continue 
to be evaluated in light of its potential impact on innovation and 
international competitiveness. To this end, the Agency is requesting 
public comment regarding the economic impacts associated with this 
proposed rule. Data or other information are specifically requested in 
connection with the following: rate of capital acquisition and critical 
factors affecting R&D capitalization; rate and magnitude of R&D 
expenditures; data regarding actual submissions under the current 
policy, e.g., project development costs, regulatory burdens, 
development schedules and revenues.

VI. Rulemaking Record and Electronic Availability of Documents

    A record has been established for this proposed rule under docket 
number ``OPPTS-00049C.'' A public version of this record which does not 
include any information claimed as CBI (see Unit VII. of this 
preamble), is available for inspection from noon to 4 p.m., Monday 
through Friday, excluding legal holidays. The public record is located 
in the TSCA Nonconfidential Information Center (NCIC) (also known as 
the TSCA Public Docket Office), Rm. NE-B607, 401 M St., SW., 
Washington, DC 20460.
    As part of an interagency ``streamlining'' initiative, EPA is 
making this proposed rule and certain support documents available 
electronically. They may be accessed through the Internet at: 
gopher.epa.gov.
    EPA is very interested in learning whether persons have obtained 
these documents electronically and what their experiences were in doing 
so. Persons who comment on this proposed rule are encouraged to provide 
feedback on this electronic availability with their comments.
    To obtain further information or to provide feedback on the 
electronic availability of these documents, please contact Juanita Geer 
(Telephone: 202-260-1532; FAX: 202-260-1657; Internet: 
[email protected]). Please be advised that Ms. Geer will 
accept only feedback on the electronic availability of these documents; 
all comments on the substance of the proposed rule must be submitted to 
the docket above.

VII. Public Record

    EPA has established a public record for this rulemaking (docket 
control number OPPTS-00049C). The record includes all information 
considered by EPA in developing this proposed rule. The record now 
includes the following items:
    1. All prior Federal Register Notices, and supporting public 
dockets, relating to the regulation of microbial products of 
biotechnology under TSCA. These include:
    a. The 1984 Proposed Policy Statement (49 FR 50856, December 31, 
1984).
    b. The 1986 Policy Statement (51 FR 23302, June 26, 1986).
    c. ``Biotechnology; Request for Comment on Regulatory Approach'', 
54 FR 7027, February 15, 1989).
    2. Public comments submitted in response to each of the above 
Notices, including the comments received at the September 1989 Meeting 
which was held to discuss TSCA regulatory options for oversight of R&D.
    3. ``Principles for Federal Oversight of Biotechnology: Planned 
Introduction Into the Environment of Organisms With Modified Hereditary 
Traits'', Office of Science and Technology Policy, 55 FR 31118, July 
31, 1990.
    4. Reports of all BSAC meetings pertaining to this proposed rule.
    5. The Regulatory Impact Analysis for this proposed rule.
    6. Support documents and reports.
    7. Records of all communications between EPA personnel and persons 
outside EPA pertaining to the development of this proposed rule. (This 
does not include any inter- or intra-agency memoranda, unless 
specifically noted in the Index of this docket.)
    8. The docket also includes published literature that is cited in 
this document.
    EPA will accept additional materials for inclusion in the record at 
any time between the date of publication of this proposed rule and the 
designation of the complete record. EPA will identify the complete 
rulemaking record by the date of promulgation of the final rule.
    Comments received on this proposed rule, along with a complete 
Index of the docket for this rulemaking, is available to the public for 
inspection from noon to 4 p.m., Monday through Friday, except legal 
holidays, in the TSCA Nonconfidential Information Center, Rm. NE-102, 
401 M St., SW., Washington, DC 20460. Only nonconfidential versions of 
documents are included in the public record.

VIII. References

    The following books, articles, and reports were used in preparing 
this notice and were cited in this notice by the number indicated 
below:
    (1) U.S. Congress, Office of Technology Assessment. 1988. ``New 
Developments in Biotechnology - Field-Testing Engineered Organisms: 
Genetic and Ecological Issues'', OTA-BA-350. U.S. Government Printing 
Office, Washington, DC.
    (2) U.S. Congress, Subcommittee on Investigations and Oversight, 
House Science, Space and Technology Committee. 1986. ``Issues in the 
Federal Regulation of Biotechnology: from Research to Releases.'' 
Washington, DC.
    (3) U.S. Environmental Protection Agency, Office of General 
Counsel, Pesticides and Toxic Substances Division. 1983. ``Status of 
recombinant DNA and new life forms under Toxic Substances Control Act 
(TSCA). Washington, DC.
    (4) U.S. Congress, Office of Technology Assessment, ``New 
Developments in Biotechnology - U.S. Investment in Biotechnology 
Summary,'' Vol. 4, p. 13. OTA-BA-401, U.S. Government Printing Office, 
Washington, DC.
    (5) Tiedje, J., Colwell, R.K., Grossman, Y.L., Hodson, R.E., 
Lenski, R.E., Mack, R.N., Regal, P.J. 1989. ``The planned introduction 
of genetically engineered organisms: Ecological considerations and 
recommendations.'' Ecology 70(2):298-315.
    (6) Schroth, M.N. 1983 ``Bacteria as biocontrol agents of plant 
disease.'' Pages 362-369 in Klug, M.J. Reddy, C.A., eds. Current 
Perspectives in Microbial Ecology. American Society for Microbiology, 
Washington, DC.
    (7) Dunigan, E.P., Bollich, P.K., Hutchinson, R.L., Hicks, P.M., 
Zaunbrecher, F.C., Scott, S.G., Mowers, R.P. 1984. ``Introduction and 
survival of an inoculant strain of Rhizobium japonicum in soil.'' 
Agronomy Journal 76:463-466.
    (8) Simberloff, D. 1986. ``Introduced insects: a biogeographic and 
systematic perspective.'' Pages 4-26 in H.A. Mooney and J.A. Drake, 
eds. Ecology of biological invasions of North America and Hawaii. 
Ecological Studies 58. SpringerVerlag, New York.
    (9) Salisbury, E. J. 1961. Weeds and Aliens. Collins, London.
    (10) Baker, H. G. 1986. ``Patterns of plant invasion in North 
America.'' Pages 44-57 in Mooney, H. A. and Drake, J. A., eds., Ecology 
of Biological Invasions of North America and Hawaii, Ecological Studies 
58. Springer-Verlag, New York.
    (11) Gill, D.M. 1982. ``Bacterial toxins: a table of lethal 
amounts.'' Microbiological Reviews 46(1): 86-94.
    (12) Gill, D.M. 1987. ``Bacterial Toxins: description.'' Laskin, 
A.I. Lechevalier, H.A., eds. Pages 3-18 in CRC Handbook of 
Microbiology, 2nd edition, Volume VIII, Toxins Enzymes. CRC Press, Boca 
Raton, FL.
    (13) Sayre, P.G. and Miller, R.V. 1991. ``Bacterial mobile genetic 
elements: Importance in assessing the environmental fate of genetically 
engineered sequences.'' Plasmid 26:151-171.
    (14) Kokjohn, T.A. 1989. ``Transduction: mechanism and potential 
for gene transfer in the environment.'' Pages 73-97 in Levy, S.B. and 
Miller, R.V., eds. Gene Transfer in the Environment. McGraw-Hill 
Publishing Co., New York.
    (15) Stotzky, G. 1989. ``Gene transfer among bacteria in soil.'' 
Pages 165-222 in Levy, S.B. and Miller, R.V., eds. Gene Transfer in the 
Environment. McGraw-Hill Publishing Co., New York.
    (16) Saye, D.J. Miller, R.V. 1989. ``The aquatic environment: 
consideration of horizontal gene transmission in a diversified 
habitat.'' Pages 223-259 in Levy, S.B. and Miller, R.V., eds. Gene 
Transfer in the Environment. McGraw-Hill Publishing Co., New York.
    (17) Jeffrey, W., Paul, J., and Stewart, G. 1990. ``Natural 
transformation of a Marine Vibrio Species by Plasmid DNA.'' Microbial 
Ecology 19:259-268.
    (18) Lewin, B., ed. 1987. Pages 55-56 in ``Genes, Third Edition.'' 
John Wiley Sons, New York.
    (19) Maki, H., Horiucki, T., and Sekiguchi, M. 1983. ``Structure 
and expression of the DNAQ mutator and RNase H genes of Escherichia 
coli: Overlap of the promoter regions.'' Proceedings of the National 
Academy of Sciences 80:7137-7141.
    (20) Ippen-Ihler, K. 1989. ``Bacterial Conjugation.'' Pages 33-72 
in Levy, S.B. and Miller, R.V., eds. 1989. Gene Transfer in the 
Environment. McGraw-Hill Publishing Co., New York.
    (21) U.S. Environmental Protection Agency, Office of Toxic 
Substances, Economics Technology Division, Chemical Engineering Branch. 
1991. ``Analysis of environmental releases and occupational exposure in 
support of proposed TSCA 5(h)(4) exemption.'' Washington, DC.
    (22) Battelle. 1988. Final Report on Biosafety in Large-Scale rDNA 
Processing Facilities. 6 volume set. U.S. EPA, Risk Reduction 
Engineering Laboratory, Cincinnati, OH.
    (23) National Institutes of Health, U.S. Department of Health Human 
Services. 1984. ``Meeting of the Large-Scale Review Working Group of 
the Recombinant DNA Advisory Committee.'' Recombinant DNA Bulletin 
7(2): 68-74.
    (24) Atlas, R. and Bartha, R. 1987. Microbial Ecology. Benjamin/
Cummings Publishing Company, Inc., Menlo Park, CA.
    (25) Francki, R.I.B., Fauquet, C.M., Knudson, D.L., Brown, F. 
(eds.) 1991. Archives of Virology/Supplementum 2. Springer-Verlag, NY., 
NY.

IX. Regulatory Assessment Requirements

A. Executive Order 12866

    Under Executive Order 12866 (58 FR 51735, October 4, 1993), the 
Agency must determine whether the regulatory action is ``significant'' 
and therefore subject to review by the Office of Management and Budget 
(OMB) and the requirements of the Executive Order. Under section 3(f), 
the order defines a ``significant regulatory action'' as an action that 
is likely to result in a rule: (1) Having an annual effect on the 
economy of $100 million or more, or adversely and materially affecting 
a sector of the economy, productivity, competition, jobs, the 
environment, public health or safety, or State, local or tribal 
governments or communities (also referred to as ``economically 
significant''); (2) creating serious inconsistency or otherwise 
interfering with an action taken or planned by another agency; (3) 
materially altering the budgetary impacts of entitlement, grants, user 
fees, or loan programs or the rights and obligations of recipients 
thereof; or (4) raising novel legal or policy issues arising out of 
legal mandates, the President's priorities, or the principles set forth 
in this Executive Order.
    Pursuant to the terms of this Executive Order, EPA has determined 
that this proposed rule is ``significant'' because it raises novel 
policy issues arising out of legal mandates. As such, this action was 
submitted to OMB for review, and any comments or changes made in 
response to OMB suggestions or recommendations have been documented in 
the public record.

B. Regulatory Flexibility Act

    Under the Regulatory Flexibility Act (5 U.S.C. 605(b)), EPA has 
analyzed the economic impact of this proposed rule on small businesses. 
A summary of this analysis appears in Unit V. of this preamble. This 
proposed rule does not exempt small businesses. Preliminary analysis of 
the impacts of this proposed rule on small businesses indicates that 
the compliance costs may have a significant impact. Despite the 
uncertainties and data gaps faced by EPA in developing this analysis, 
EPA believes that it is prudent public policy to assume that the 
requirements of the Regulatory Flexibility Act (Pub. L. 96-354) have 
been triggered. EPA believes that review of certain new microorganisms 
under TSCA is important to ensure that there are no unreasonable risks 
to health and the environment, and that the mechanisms outlined in this 
proposed rule will lessen impacts on small business as much as 
possible.
    The Regulatory Impact Analysis section on small business impacts 
(Section VIII of the RIA, which is part of the public record for this 
rulemaking) serves as the Initial Regulatory Flexibility Analysis 
required by the Regulatory Flexibility Act. EPA intends to revise this 
analysis prior to promulgation of the final rule. EPA requests comments 
on the methodology employed in this analysis and the results of this 
analysis.

C. Paperwork Reduction Act

    The Office of Management and Budget (OMB) has approved the current 
Premanufacture Notification and SNUR program under the provisions of 
the Paperwork Reduction Act, 44 U.S.C. 3501 et seq. and has assigned 
OMB control number 2070-0012. This proposed rule, when promulgated, 
would modify those information collection requirements; an information 
collection request addressing these modifications has been submitted to 
OMB under the provisions of the Paperwork Reduction Act, 44 U.S.C. 3501 
et seq.
    Public reporting burden for this collection of information is 
estimated to average 473 hours per response, including time for 
reviewing instructions, searching existing data sources, gathering and 
maintaining the data needed, and completing and reviewing the 
collection of information.
    Send comments regarding the burden estimate or any other aspect of 
this collection of information, including suggestions for reducing 
burden, to Chief, Information Policy Branch, 2136, U.S. Environmental 
Protection Agency, 401 M St., SW., Washington, DC 20460, and to the 
Office of Information and Regulatory Affairs, Office of Management and 
Budget, Washington, DC 20503, marked ``Attention: Desk Officer for 
EPA.'' The final rule will respond to any OMB or public comments on the 
information collection requirements contained in this proposal.

List of Subjects in 40 CFR Parts 700, 720, 721, 723, and 725

    Environmental protection, Administrative practice and procedure, 
Biotechnology, Chemicals, Hazardous substances, Imports, Labeling, 
Microorganisms, Occupational safety and health, Reporting and 
recordkeeping requirements

    Dated: August 19, 1994.
Carol M. Browner,
Administrator.

    Therefore, it is proposed that 40 CFR Chapter I be amended as 
follows:

PART 700--[AMENDED]

    1. In part 700:
    a. The authority citation for part 700 would continue to read as 
follows:

    Authority: 15 U.S.C. 2625.

    b. In Sec. 700.43, by revising the introductory text and the 
definition of ``Section 5 notice'' and adding two definitions to read 
as follows:


Sec. 700.43   Definitions.

    Definitions in section 3 of the Act (15 U.S.C. 2602), as well as 
definitions contained in Sec. Sec. 704.3, 720.3, and 725.3 of this 
chapter, apply to this subpart unless otherwise specified in this 
section. In addition, the following definitions apply:
    Consolidated microbial commercial activity notice or consolidated 
MCAN means any MCAN submitted to EPA that covers more than one 
microorganism (each being assigned a separate MCAN number by EPA) as a 
result of a prenotice agreement with EPA.
     *  *  *  *  *
    Microbial commercial activity notice or MCAN means any notice for 
microorganisms submitted to EPA pursuant to section 5(a)(1) of the Act 
in accordance with subpart D of part 725 of this chapter.
     *  *  *  *  *
    Section 5 notice means any PMN, consolidated PMN, intermediate PMN, 
significant new use notice, exemption notice, exemption application, 
any MCAN or consolidated MCAN submitted under section 5 of TSCA.
     *  *  *  *  *
    c. In Sec. 700.45 by adding paragraphs (b)(2)(vi), (e)(4)(iv), 
(e)(5)(iv), (f)(4), and revising paragraphs (c) and (f)(3) to read as 
follows:


Sec. 700.45  Fee payments.

    *  *  *  *  *
    (b) *  *  *
    (2) *  *  *
    (vi) MCAN and consolidated MCAN. Persons shall remit a fee of 
$2,500 for each MCAN or consolidated MCAN submitted.
    (c) No fee required. Persons are exempt from remitting any fee for 
submissions under Sec. Sec. 720.38, 723.50, and subparts E, F, and G of 
part 725 of this chapter.
     *  *  *  *  *  
    (e) *  *  *
    (4) *  *  *
    (iv) Each person who remits the fee identified in paragraph (b)(1) 
of this section for a MCAN for a microorganism shall include the words, 
``The company identified in this notice is a small business concern 
under 40 CFR 700.43 and has remitted a fee of $100 in accordance with 
40 CFR 700.45(d),'' in the certification required in Sec. 725.25(b) of 
this chapter.
    (5) *  *  *
    (iv) Each person who remits a fee identified in paragraph (b)(2) of 
this section for a MCAN for a microorganism shall include the words, 
``The company identified in this notice has remitted the fee specified 
in 40 CFR 700.45(b),'' in the certification required in Sec. 725.25(b) 
of this chapter.
    (f) *  *  *
    (3) The notice is incomplete under either Sec. 720.65(c) or 725.33, 
of this chapter.
    (4) That as of the date of submission of the notice: the 
microorganism that is the subject of a MCAN is not a new microorganism; 
nor is the use involving the microorganism a significant new use.
    d. By revising Sec. 700.49 to read as follows:


Sec. 700.49   Failure to remit fees.

    EPA will not consider a section 5 notice to be complete unless the 
appropriate certification under Sec. 700.45(e) is included and until 
the appropriate remittance under Sec. 700.45(b) has been sent to EPA as 
provided in Sec. 700.45(e) and received by EPA. EPA will notify the 
submitter that the section 5 notice is incomplete in accordance with 
Sec. Sec. 720.65(c) and 725.33 of this chapter.

PART 720 -- [AMENDED]

    2. In part 720:
    a. The authority citation for part 720 would continue to read as 
follows:

    Authority: 15 U.S.C. 2604, 2607, and 2613.

    b. In Sec. 720.1, by revising the first sentence and adding a 
sentence to read as follows:


Sec. 720.1   Scope.

    This part establishes procedures for the reporting of new chemical 
substances by manufacturers and importers under section 5 of the Toxic 
Substances Control Act, 15 U.S.C. 2604. This part applies to 
microorganisms only to the extent provided by part 725 of this chapter. 
*  *  *  

PART 721 -- [AMENDED]

    3. In part 721:
    a. The authority citation for part 721 would continue to read as 
follows:

    Authority: 15 U.S.C. 2604, 2607, and 2625(c).

    b. In Sec. 721.1(a), by revising the first sentence to read as 
follows:


Sec. 721.1   Scope and applicability.

    This part identifies uses of chemical substances, except for 
microorganisms regulated under part 725 of this chapter, which EPA has 
determined are significant new uses under the authority of section 
5(a)(2) of the Toxic Substances Control Act. *  *  *  

PART 723 -- [AMENDED]

    4. In part 723:
    a. The authority citation for part 723 would continue to read as 
follows:

    Authority: 15 U.S.C. 2604.

    b. In Sec. 723.50, by revising paragraph (a)(1) to read as follows:


Sec. 723.50   Chemical substances manufactured in quantities of 1,000 
kilograms or less per year.

    (a) Purpose and scope. (1) This section grants an exemption from 
the premanufacture notice requirements of section 5(a)(1)(A) of the 
Toxic Substances Control Act (15 U.S.C. 2604(a)(1)(A)) for the 
manufacture of certain chemical substances manufactured in quantities 
of 1,000 kilograms or less per year. This section does not apply to 
microorganisms regulated under part 725 of this chapter.
    *  *  *  *  *  
    c. In Sec. 723.175, by revising paragraph (a)(1) to read as 
follows:


Sec. 723.175   Chemical substances used in or for the manufacture or 
processing of instant photographic and peel-apart film articles.

    (a) Purpose and scope. (1) This section grants an exemption from 
the premanufacture notice requirements of section 5(a)(1)(A) of the 
Toxic Substances Control Act (15 U.S.C. 2604(a)(1)(A)) for the 
manufacture and processing of new chemical substances used in or for 
the manufacture or processing of instant photographic and peel-apart 
film articles. This section does not apply to microorganisms regulated 
under part 725 of this chapter.
    *  *  *  *  *  
    d. In Sec. 723.250, by revising paragraph (a)(1) to read as 
follows:


Sec. 723.250   Polymers.

    (a) Purpose and scope. (1) This section grants an exemption from 
the premanufacture notice requirements of section 5(a)(1)(A) of the 
Toxic Substances Control Act (15 U.S.C. 2604(a)(1)(A)) for the 
manufacture of certain polymers. This section does not apply to 
microorganisms regulated under part 725 of this chapter.
    *  *  *  *  *  
    5. Part 725 is added to read as follows:

PART 725--REPORTING REQUIREMENTS AND REVIEW PROCESSES FOR 
MICROORGANISMS

Subpart A--General Provisions and Applicability
Sec.
725.1    Scope and purpose.
725.3    Definitions.
 725.8    Coverage of this part.
725.12   Identification of microorganisms for Inventory and other 
listing purposes.
725.15   Determining applicability when microorganism identity or 
use is confidential or uncertain.
725.17   Consultation with EPA.
Subpart B--Administrative Procedures
725.20   Scope and purpose.
725.25   General administrative requirements.
725.27   Submissions.
725.28   Notice that submission is not required.
725.29   EPA acknowledgement of receipt of submission.
725.32   Errors in the submission.
725.33   Incomplete submissions.
725.36   New information.
725.40   Notice in the Federal Register.
725.50   EPA review.
725.54   Suspension of the review period.
725.56   Extension of the review period.
725.60   Withdrawal of submission by the submitter.
725.65   Recordkeeping.
725.67   Applications to exempt new microorganisms from this part.
725.70   Compliance.
725.75   Inspections.
Subpart C--Confidentiality and Public Access to Information
725.80   General provisions for confidentiality claims.
725.85   Microorganism identity.
725.88   Uses of a microorganism.
725.92   Data from health and safety studies of microorganisms.
725.94   Substantiation requirements.
725.95   Public file.
Subpart D--Microbial Commercial Activities Notification Requirements
725.100   Scope and purpose.
725.105   Persons who must report.
725.110   Persons not subject to this subpart.
725.150   Procedural requirements for this subpart.
725.155   Information to be included in the MCAN.
725.160   Submission of health and environmental effects data.
725.170   EPA review of the MCAN.
725.190   Notice of commencement of manufacture or import.
Subpart E--Exemptions for Research and Development Activities
725.200   Scope and purpose.
725.205   Persons who may report under this subpart.
725.232   Activities subject to the jurisdiction of other Federal 
programs or agencies.
725.234   Activities conducted inside a structure.
725.235   Conditions of exemption for activities conducted inside a 
structure.
725.238   Activities conducted outside a structure.
725.239   Use of specific microorganisms in activities conducted 
outside a structure.
725.250   Procedural requirements for this subpart.
725.255   Information to be included in the TERA.
725.260   Submission of health and environmental effects data.
725.270   EPA review of the TERA.
725.288   Revocation or modification of TERA approval.
Subpart F--Exemptions for Test Marketing
725.300   Scope and purpose.
725.305   Persons who may report under this subpart.
725.350   Procedural requirements for this subpart.
725.355   Information to be included in the TME application.
725.370   EPA review of the TME application.
Subpart G--Exemption for Microorganisms in General Commercial Use
725.400   Scope and purpose.
725.420   Recipient microorganisms.
725.421   Introduced genetic material.
725.422   Physical containment and control technologies.
725.424   Requirements for the Tier I exemption.
725.426   Liability of the manufacturer or importer who uses the 
Tier I exemption.
725.428   Requirements for the Tier II exemption.
725.450   Procedural requirements for the Tier II exemption.
725.455   Information to be included in the Tier II exemption 
request.
725.470   EPA review of the Tier II exemption request.
Subparts H--K [Reserved]
Subpart L--Additional Procedures Applicable to Reporting on Significant 
New Uses of Microorganisms
725.900   Scope and purpose.
725.910   Persons excluded from reporting of significant new uses.
725.912   Exemptions.
725.920   Exports and imports.
725.950   Additional recordkeeping requirements for reporting of 
significant new uses.
725.975   EPA approval of alternative control measures.
725.980   Expedited procedures for issuing significant new use rules 
for microorganisms subject to section 5(e) orders.
725.984   Modification or revocation of certain notification 
requirements.
Subpart M--Significant New Uses for Specific Microorganisms--[Reserved]

    Authority: 15 U.S.C. 2604, 2607, 2613, and 2625.

Subpart A--General Provisions and Applicability


Sec. 725.1  Scope and purpose.

    (a) This part establishes reporting requirements under section 5 of 
TSCA for manufacturers, importers, and processors of microorganisms for 
commercial purposes.
    (b) TSCA section 5 covers chemical substances as defined under TSCA 
section 3. Because EPA interprets the section 3 definition to include 
microorganisms, section 5 also covers microorganisms. Unless otherwise 
specifically stated in the Code of Federal Regulations, TSCA section 5 
authority over microorganisms (as distinguished from other chemical 
substances) will be implemented under this part.
    (c) Microorganisms subject to reporting as new microorganisms will 
be those which are intergeneric. In addition, any microorganism subject 
to TSCA jurisdiction may be subject to reporting, if EPA determines by 
rule that the microorganism is being manufactured, imported, or 
processed for a significant new use.
    (d) This subpart A describes the general organization for this part 
and contains definitions generally applicable to this part.
    (e) Subpart B of this part describes general administrative 
procedures applicable to microorganisms subject to this part.
    (f) Subpart C of this part establishes requirements for handling 
confidential business information (CBI) and public access to 
information submitted under this part.
    (g) Subpart D of this part describes the persons and microorganisms 
subject to Microorganism Commercial Activity Notices (MCANs), 
prescribes the content of MCANs, and establishes procedures for 
reviewing MCANs.
    (h) Subpart E of this part establishes reporting requirements and 
EPA review procedures for the TSCA Experimental Release Application 
(TERA) for microorganisms intentionally tested in the environment 
during commercial research and development activities. Subpart E of 
this part also identifies microorganisms and classes of microorganisms 
exempt from research and development reporting.
    (i) Subpart F of this part establishes procedures for obtaining 
test marketing exemptions (TMEs) for microorganisms.
    (j) Subpart G of this part identifies microorganisms in general 
commercial use under certain conditions of containment that are 
eligible for Tier I and Tier II exemptions from subpart D reporting. 
Subpart G of this part establishes reporting requirements and 
procedures for expedited review of the Tier II exemption request.
    (k) Subpart L of this part describes additional requirements 
applicable to reporting on microorganisms subject to significant new 
use rules under TSCA section 5(a)(2). All significant new uses of 
microorganisms are subject to the MCAN requirements in subpart D of 
this part.
    (l) Subpart M of this part identifies specific significant new uses 
of microorganisms subject to subpart D reporting.


Sec. 725.3   Definitions.

    Definitions in section 3 of the Act (15 U.S.C. 2602), as well as 
definitions contained in Sec. Sec. 704.3, 720.3, and 721.3 of this 
chapter, apply to this part unless otherwise specified in this section. 
In addition, the following definitions apply to this part:
    Consolidated microbial commercial activity notice or consolidated 
MCAN means any MCAN submitted to EPA that covers more than one 
microorganism (each being assigned a separate MCAN number by EPA) as a 
result of a prenotice agreement with EPA.
    Containment and/or inactivation controls means any combination of 
engineering, mechanical, procedural, or biological controls designed 
and operated to restrict environmental release of viable microorganisms 
from a structure.
    Director means the Director of the EPA Office of Pollution 
Prevention and Toxics.
    Exemption request means any application submitted to EPA under 
subparts E, F, or G of this part.
    General commercial use means use for commercial purposes other than 
research and development.
    Genome means the sum total of chromosomal and extrachromosomal 
genetic material of an isolate and any descendants derived under pure 
culture conditions from that isolate.
    Health and safety study of a microorganism or health and safety 
study means any study of any effect of a microorganism or microbial 
mixture on health or the environment or on both, including underlying 
data and epidemiological studies, studies of occupational exposure to a 
microorganism or microbial mixture, toxicological, clinical, and 
ecological, or other studies of a microorganism or microbial mixture, 
and any test performed under the Act. Microorganism identity is always 
part of a health and safety study of a microorganism.
    (1) It is intended that the term ``health and safety study of a 
microorganism'' be interpreted broadly. Not only is information which 
arises as a result of a formal, disciplined study included, but other 
information relating to the effects of a microorganism or microbial 
mixture on health or the environment is also included. Any data that 
bear on the effects of a microorganism on health or the environment 
would be included.
    (2) Examples include:
    (i) Tests for ecological or other environmental effects on 
invertebrates, fish, or other animals, and plants, including: Acute 
toxicity tests, chronic toxicity tests, critical life stage tests, 
behavioral tests, algal growth tests, seed germination tests, plant 
growth or damage tests, microbial function tests, bioconcentration or 
bioaccumulation tests, and model ecosystem (microcosm) studies.
    (ii) Long- and short-term tests of mutagenicity, carcinogenicity, 
or teratogenicity; dermatoxicity; cumulative, additive, and synergistic 
effects; and acute, subchronic, and chronic effects.
    (iii) Assessments of human and environmental exposure, including 
workplace exposure, and impacts of a particular microorganism or 
microbial mixture on the environment, including surveys, tests, and 
studies of: Survival and transport in air, water, and soil; ability to 
exchange genetic material with other microorganisms, ability to 
colonize human or animal guts, and ability to colonize plants.
    (iv) Monitoring data, when they have been aggregated and analyzed 
to measure the exposure of humans or the environment to a 
microorganism.
    (v) Any assessments of risk to health and the environment resulting 
from the manufacture, processing, distribution in commerce, use, or 
disposal of the microorganism.
    Inactivation means that living microorganisms are rendered 
nonviable. ``Introduced genetic material'' means genetic material that 
is added to, and remains as a component of, the genome of the 
recipient.
    Intergeneric microorganism means a microorganism that is formed by 
the deliberate combination of genetic material from organisms of 
different taxonomic genera, including mobile genetic elements. The term 
``intergeneric microorganism'' does not include a microorganism which 
contains genetic material consisting of only well-characterized, non-
coding regulatory regions from another genus.
    Introduced genetic material means genetic material that is added 
to, and remains as a component of, the genome of the recipient.
    Manufacture, import, or process for commercial purposes means: (1) 
To import, produce, manufacture, or process with the purpose of 
obtaining an immediate or eventual commercial advantage for the 
manufacturer, importer, or processor, and includes, among other things, 
``manufacture'' or ``processing'' of any amount of a microorganism or 
microbial mixture:
    (i) For commercial distribution, including for test marketing.
    (ii) For use by the manufacturer, including use for product 
research and development or as an intermediate.
    (2) The term also applies to substances that are produced 
coincidentally during the manufacture, processing, use, or disposal of 
another microorganism or microbial mixture, including byproducts that 
are separated from that other microorganism or microbial mixture and 
impurities that remain in that microorganism or microbial mixture. 
Byproducts and impurities without separate commercial value are 
nonetheless produced for the purpose of obtaining a commercial 
advantage, since they are part of the manufacture or processing of a 
microorganism for commercial purposes.
    Microbial commercial activity notice or MCAN means a notice for 
microorganisms submitted to EPA pursuant to subpart D of this part.
    Microbial mixture means any combination of microorganisms or 
microorganisms and other chemical substances, if the combination does 
not occur in nature and is not an article.
    Microorganism means an organism classified in the kingdoms Monera 
(or Procaryotae), Protista, Fungi, and the Chlorophyta and the 
Rhodophyta of the Plantae, and a virus or virus-like particle.
    Mobile genetic element or MGE means an element of genetic material 
that has the ability to move genetic material within and between 
organisms. ``Mobile genetic elements'' include all plasmids, viruses, 
transposons, insertion sequences, and other classes of elements with 
these general properties.
    New microorganism means a microorganism not included on the TSCA 
Inventory.
    Small quantities solely for research and development (or ``small 
quantities solely for purposes of scientific experimentation or 
analysis or research on, or analysis of, such substance or another 
substance, including such research or analysis for development of a 
product'') means quantities of a microorganism manufactured, imported, 
or processed or proposed to be manufactured, imported, or processed 
solely for research and development that meet the requirements of 
Sec. 725.234.
    Structure means a building or vessel which effectively surrounds 
and encloses the microorganism and includes features designed to 
restrict the microorganism from leaving.
    Submission means any MCAN or exemption request submitted to EPA 
under this part.
    Technically qualified individual means a person or persons (1) Who, 
because of education, training, or experience, or a combination of 
these factors, is capable of understanding the health and environmental 
risks associated with the microorganism which is used under his or her 
supervision, (2) who is responsible for enforcing appropriate methods 
of conducting scientific experimentation, analysis, or microbiological 
research to minimize such risks, and (3) who is responsible for the 
safety assessments and clearances related to the procurement, storage, 
use, and disposal of the microorganism as may be appropriate or 
required within the scope of conducting a research and development 
activity.
    TSCA Experimental Release Application or TERA means an exemption 
request for a research and development activity, which is not eligible 
for a full exemption from reporting under Sec. 725.232, 725.234, or 
725.238 of this part, submitted to EPA in accordance with subpart E of 
this part.
    Well-characterized, non-coding regulatory region means a segment of 
genetic material for which:
    (1) The exact nucleotide base sequences of the regulatory region 
and any inserted flanking nucleotides are known and documented.
    (2) The regulatory region and any inserted flanking nucleotides do 
not code for protein, peptide, or functional ribonucleic acid 
molecules.
    (3) The regulatory region solely controls the activity of other 
regions that code for protein or peptide molecules or act as 
recognition sites for the initiation of nucleic acid or protein 
synthesis.


Sec. 725.8   Coverage of this part.

    (a) Microorganisms subject to this part. Only microorganisms which 
are manufactured, imported, or processed for commercial purposes, as 
defined in Sec. 725.3 of this part, are subject to the requirements of 
this part.
    (b) Microoganisms automatically included on the Inventory. 
Microorganisms that are not intergeneric are automatically included on 
the TSCA Inventory.
    (c) Microorganisms not subject to this part. The following 
microorganisms are not subject to this part, either because they are 
not subject to TSCA jurisdiction or are not subject to reporting under 
TSCA section 5.
    (1) Any microorganism which would be excluded from the definition 
of ``chemical substance'' in section 3 of TSCA and Sec. 720.3(e) of 
this chapter.
    (2) Any microbial mixture as defined in Sec. 725.3 of this part. 
This exclusion applies only to a microbial mixture as a whole and not 
to any microorganisms and other chemical substances which are part of 
the microbial mixture.
    (3) Any microorganism that is manufactured and processed solely for 
export if the following conditions are met:
    (i) The microorganism is labeled in accordance with section 
12(a)(1)(B) of TSCA, when the microorganism is distributed in commerce.
    (ii) The manufacturer and processor can document at the 
commencement of manufacturing or processing that the person to whom the 
microorganism will be distributed intends to export it or process it 
solely for export as defined in Sec. 721.3 of this chapter.


Sec. 725.12   Identification of microorganisms for Inventory and other 
listing purposes.

    To identify and list microorganisms on the Inventory, both 
taxonomic designations and supplemental information will be used. The 
supplemental information required in paragraph (b) of this section will 
be used to specifically describe an individual microorganism on the 
Inventory. Submitters must provide the supplemental information 
required by paragraph (b) of this section to the extent necessary to 
enable a microorganism to be accurately and unambiguously identified on 
the Inventory.
    (a) Taxonomic designation. The taxonomic designation of a 
microorganism must be provided for the donor organism and the recipient 
microorganism to the level of strain, as appropriate. These 
designations must be substantiated by a letter from a culture 
collection, literature references, or the results of tests conducted 
for the purpose of taxonomic classification. Upon EPA's request to the 
submitter, data supporting the taxonomic designation must be provided 
to EPA. The genetic history of the recipient microorganism should be 
documented back to the isolate from which it was derived.
    (b) Supplemental information. The supplemental information 
described in paragraphs (b)(1) and (b)(2) of this section is required 
to the extent that it enables a microorganism to be accurately and 
unambiguously identified.
    (1) Phenotypic information. Phenotypic information means pertinent 
traits that result from the interaction of a microorganism's genotype 
and the environment in which it is intended to be used and may include 
intentionally added biochemical and physiological traits.
    (2) Genotypic information. Genotypic information means the 
pertinent and distinguishing genotypic characteristics of a 
microorganism, such as the identity of the introduced genetic material 
and the methods used to construct the reported microorganism. This also 
may include information on the vector construct, the cellular location, 
and the number of copies of the introduced genetic material.


Sec. 725.15   Determining applicability when microorganism identity or 
use is confidential or uncertain.

    (a) Consulting EPA. Persons intending to conduct activities 
involving microorganisms may determine their obligations under this 
part by consulting the TSCA Inventory or the microorganisms and uses 
specified in Sec. 725.239 or subpart M of this part. This section 
establishes procedures for EPA to assist persons in determining whether 
the microorganism or the use is listed on the Inventory or in 
Sec. 725.239 or subpart M of this part.
    (1) Confidential identity or use. In some cases it may not be 
possible to directly determine if a specific microorganism is listed, 
because portions of that entry may contain generic information to 
protect confidential business information (CBI). If any portion of the 
microorganism's identity or use has been claimed CBI, that portion does 
not appear on the public version of the Inventory, in Sec. 725.239 or 
in subpart M of this part. Instead, it is contained in a confidential 
version held in EPA's Confidential Business Information Center (CBIC). 
The public versions contain generic information which masks the 
confidential business information. A person who intends to conduct an 
activity involving a microorganism or use whose entry is described with 
generic information will need to inquire of EPA whether the unreported 
microorganism or use is on the confidential version.
    (2) Uncertain microorganism identity. The current state of 
scientific knowledge leads to some imprecision in describing a 
microorganism. As the state of knowledge increases, EPA will be 
developing policies to determine whether one microorganism is 
equivalent to another. Persons intending to conduct activities 
involving microorganisms may inquire of EPA whether the microorganisms 
they intend to manufacture, import, or process are equivalent to 
specific microorganisms described on the Inventory, in Sec. 725.239 or 
subpart M of this part.
    (b) Requirement of bona fide intent. (1) EPA will answer the 
inquiries described in paragraph (a) of this section only if the Agency 
determines that the person has a bona fide intent to conduct the 
activity for which reporting is required or for which any exemption may 
apply.
    (2) To establish a bona fide intent to manufacture, import, or 
process a microorganism, the person who intends to manufacture, import, 
or process the microorganism must submit the following information in 
writing to the Office of Pollution Prevention and Toxics, Document 
Control Officer, 7407, 401 M St., SW., Washington, DC 20460, ATTN: 
BIOTECH bona fide submission.
    (i) Taxonomic designations and supplemental information required by 
Sec. 725.12.
    (ii) A signed statement certifying that the submitter intends to 
manufacture, import, or process a microorganism for commercial 
purposes.
    (iii) A description of research and development activities 
conducted with the microorganism to date, demonstration of the 
submitter's ability to produce or obtain the microorganism from a 
foreign manufacturer, and the purpose for which the person will 
manufacture, import, or process the microorganism.
    (iv) An indication of whether a related microorganism was 
previously reviewed by the Agency to the extent known by the submitter.
    (c) If an importer or processor cannot provide all the information 
required by paragraph (b) of this section, because it is claimed as 
confidential business information by its foreign manufacturer or 
supplier, the foreign manufacturer or supplier may supply the 
information directly to EPA.
    (d) EPA will review the information submitted by the manufacturer, 
importer, or processor under this paragraph to determine whether that 
person has shown a bona fide intent to manufacture, import, or process 
the microorganism. If necessary, EPA will compare this information to 
the information requested for the confidential microorganism under 
Sec. 725.85(b)(3)(iii).
    (e) In order for EPA to make a conclusive determination of the 
microorganism's status, the proposed manufacturer, importer, or 
processor must show a bona fide intent to manufacture, import, or 
process the microorganism and must provide sufficient information to 
establish identity unambiguously. After sufficient information has been 
provided, EPA will inform the manufacturer, importer, or processor 
whether the microorganism is subject to this part and if so, which 
sections of this part apply.
    (f) If the microorganism is found on the confidential version of 
the Inventory, in Sec. 725.239 or subpart M of this part, EPA will 
notify the person(s) who originally reported the microorganism that 
another person (whose identity will remain confidential, if so 
requested) has demonstrated a bona fide intent to manufacture, import, 
or process the microorganism and therefore was told that the 
microorganism is subject to this part.
    (g) A disclosure to a person with a bona fide intent to 
manufacture, import, or process a particular microorganism that the 
microorganism is subject to this part will not be considered a public 
disclosure of confidential business information under section 14 of the 
Act.
    (h) EPA will answer an inquiry on whether a particular 
microorganism is subject to this part within 30 days after receipt of a 
complete submission under paragraph (b) of this section.


Sec. 725.17  Consultation with EPA.

    Persons may consult with EPA, either in writing or by telephone, 
about their obligations under this part. Written consultation is 
preferred. Written inquiries should be sent to the following address: 
Environmental Assistance Division (7408), Office of Pollution 
Prevention and Toxics, U.S. Environmental Protection Agency, 401 M St., 
SW., Washington, DC 20460, ATTN: Biotechnology Notice Consultation. 
Persons wishing to consult with EPA by telephone should call (202) 554-
1404; hearing impaired TDD (202) 554-0551.
Subpart B--Administrative Procedures


Sec. 725.20   Scope and purpose.

    This subpart describes general administrative procedures applicable 
to all persons who submit MCANs and exemption requests to EPA under 
section 5 of the Act for microorganisms.


Sec. 725.25   General administrative requirements.

    (a) General. (1) Each person who is subject to the notification 
provisions of this part must complete, sign, and submit a MCAN or 
exemption request containing the information as required for the 
appropriate submission under this part. Except as otherwise provided, 
each submission must include all referenced attachments. All 
information in the submission (unless certain attachments appear in the 
open scientific literature) must be in English. All information 
submitted must be true and correct.
    (2) In addition to specific information required, the submitter 
should submit all information known to or reasonably ascertainable by 
the submitter that would permit EPA to make a reasoned evaluation of 
the human health and environmental effects of the microorganism and any 
microbial mixture or article that may contain the microorganism.
    (b) Certification. Persons submitting MCANs and exemption requests 
to EPA under this part, and material related to their reporting 
obligations under this part, must attach the following statement to any 
information submitted to EPA:

    I certify that to the best of my knowledge and belief: The 
company named in this submission intends to manufacture, import, or 
process for a commercial purpose, other than in small quantities 
solely for research and development, the microorganism identified in 
this submission. All information provided in this submission is 
complete and truthful as of the date of submission. I am including 
with this submission all test data in my possession or control and a 
description of all other data known to or reasonably ascertainable 
by me as required by 40 CFR 725.160 or 725.260.

This statement must be signed and dated by an authorized official of 
the submitter.
    (c) Where to submit information under this part. Persons submitting 
MCANs and exemption requests to EPA under this part, and material 
related to their reporting obligations under this part, must send them 
to: TSCA Document Processing Center (7407), Rm. L-100, Office of 
Pollution Prevention and Toxics, U.S. Environmental Protection Agency, 
401 M St., SW., Washington, DC 20460.
    (d) General requirements for submission of data. (1) Submissions 
under this part must include the information described in Sec. 725.155, 
725.255, 725.355, or 725.455, as appropriate, to the extent such 
information is known to or reasonably ascertainable by the submitter.
    (2) In accordance with Sec. 725.160 or 725.260, as appropriate, the 
submission must also include any test data in the submitter's 
possession or control and descriptions of other data which are known to 
or reasonably ascertainable by the submitter and which concern the 
health and environmental effects of the microorganism.
    (e) Agency or joint submissions. (1) A manufacturer or importer may 
designate an agent to submit the MCAN or exemption request. Both the 
manufacturer or importer and the agent must sign the certification 
required in paragraph (b) of this section.
    (2) A manufacturer or importer may authorize another person (e.g., 
a foreign manufacturer or supplier, or a toll manufacturer) to report 
some of the information required in theMCAN or exemption request to EPA 
on its behalf. If separate portions of a joint submission are not 
submitted together, the submitter must indicate which information will 
be supplied by another person and identify that person. The 
manufacturer or importer and any other person supplying the information 
must sign the certification required by paragraph (b) of this section.
    (3) If EPA receives a submission which does not include the 
information required, which the submitter indicates that it has 
authorized another person to provide, the review period will not begin 
until EPA receives all of the required information.
    (f) Microorganisms subject to a section 4 test rule. (1) Except as 
provided in paragraph (f)(3) of this section, if (i) A person intends 
to manufacture or import a new microorganism which is subject to the 
notification requirements of this part, and (ii) the microorganism is 
subject to a test rule promulgated under section 4 of the Act before 
the notice is submitted, section 5(b)(1) of the Act requires the person 
to submit the test data required by the testing rule with the notice. 
The person must submit the data in the form and manner specified in the 
test rule and in accordance with Sec. 725.160. If the person does not 
submit the test data, the submission is incomplete and EPA will follow 
the procedures in Sec. 725.33.
    (2) If EPA has granted the submitter an exemption under section 
4(c) of the Act from the requirement to conduct tests and submit data, 
the person may not file a MCAN or TERA until EPA receives the test 
data.
    (3) If EPA has granted the submitter an exemption under section 
4(c) of the Act and if another person previously has submitted the test 
data to EPA, the exempted person may either submit the test data or 
provide the following information as part of the notice:
    (i) The name, title, and address of the person who submitted the 
test data to EPA.
    (ii) The date the test data were submitted to EPA.
    (iii) A citation for the test rule.
    (iv) A description of the exemption and a reference identifying it.
    (g) Microorganisms subject to a section 5(b)(4) rule. (1) If a 
person (i) Intends to manufacture or import a microorganism which is 
subject to the notification requirements of this part and which is 
subject to a rule issued under section 5(b)(4) of the Act; and (ii) is 
not required by a rule issued under section 4 of the Act to submit test 
data for the microorganism before the filing of a submission, the 
person must submit to EPA data described in paragraph (g)(2) of this 
section at the time the submission is filed.
    (2) Data submitted under paragraph (g)(1) of this section must be 
data which the person submitting the notice believes show that the 
manufacture, processing, distribution in commerce, use, and disposal of 
the microorganism, or any combination of such activities, will not 
present an unreasonable risk of injury to health or the environment.
    (h) Data that need not be submitted. Specific data requirements are 
listed in subparts D, E, F, G, and L of this part. The following is a 
list of data that need not be submitted under this part:
    (1) Data previously submitted to EPA. (i) A person need not submit 
any data previously submitted to EPA with no claims of confidentiality 
if the new submission includes: the office or person to whom the data 
were submitted; the date of submission; and, if appropriate, a standard 
literature citation as specified in Sec. 725.160(a)(3)(ii).
    (ii) For data previously submitted to EPA with a claim of 
confidentiality, the person must resubmit the data with the new 
submission and any claim of confidentiality, under Sec. 725.80.
    (2) Efficacy data. This part does not require submission of any 
data related solely to product efficacy. However, including efficacy 
data will improve EPA's ability to assess the benefits of the use of 
the microorganism. This does not exempt a person from submitting any of 
the data specified in Sec. 725.160 or 725.260.
    (3) Non-U.S. exposure data. This part does not require submission 
of any data which relates only to exposure of humans or the environment 
outside the United States. This does not exclude nonexposure data such 
as data on health effects (including epidemiological studies), 
ecological effects, physical and chemical properties, or environmental 
fate characteristics.


Sec. 725.27   Submissions.

    Each person who is required to submit information under this part 
must submit the information in the form and manner set forth in the 
appropriate subpart.
    (a) Requirements specific to MCANs are described in 
Sec. Sec. 725.150 through 725.160.
    (b) Requirements specific to TERAs are described in 
Sec. Sec. 725.250 through 725.260.
    (c) Requirements specific to test marketing exemptions (TMEs) are 
described in Sec. Sec. 725.350 and 725.355.
    (d) Requirements specific to Tier I and Tier II exemptions for 
certain general commercial uses are described in Sec. Sec. 725.424 
through 725.460.
    (e) Additional requirements specific to significant new uses for 
microorganisms are described at Sec. 725.950.


Sec. 725.28   Notice that submission is not required.

    When EPA receives a MCAN or exemption request, EPA will review it 
to determine whether the microorganism is subject to the requirements 
of this part. If EPA determines that the microorganism is not subject 
to these requirements, EPA will notify the submitter that section 5 of 
the Act does not prevent the manufacture, import, or processing of the 
microorganism and that the submission is not needed.


Sec. 725.29   EPA acknowledgement of receipt of submission.

    (a) EPA will acknowledge receipt of each submission by sending the 
submitter a letter that identifies the number assigned to the new 
microorganism and the date on which the review period begins. The 
review period will begin on the date the MCAN or exemption request is 
received by the Office of Pollution Prevention and Toxics Document 
Control Officer.
    (b) The acknowledgement does not constitute a finding by EPA that 
the submission is in compliance with this part.


Sec. 725.32   Errors in the submission.

    (a) Within 30 days of receipt of the submission, EPA may request 
that the submitter remedy errors in the submission. The following are 
examples of such errors:
    (1) Failure to date the submission.
    (2) Typographical errors that cause data to be misleading or 
answers to any questions to be unclear.
    (3) Contradictory information.
    (4) Ambiguous statements or information.
    (b) In the request to correct the submission, EPA will explain the 
action which the submitter must take to correct the submission.
    (c) If the submitter fails to correct the submission within 15 days 
of receipt of the request, EPA may extend the review period.


Sec. 725.33   Incomplete submissions.

    (a) A submission under this part is not complete, and the review 
period does not begin, if:
    (1) The wrong person files the submission.
    (2) The submitter does not attach and sign the certification 
statement as required by Sec. 725.25(b).
    (3) Some or all of the information in the submission or any 
attachments are not in English, except for published scientific 
literature.
    (4) The submitter does not provide information that is required by 
sections 5(d)(1)(B) and (C) of the Act and Sec. 725.160 or 725.260, as 
appropriate.
    (5) The submitter does not provide information required by 
Sec. 725.25, 725.155, 725.255, 725.355, or 725.455, as appropriate, or 
indicate that it is not known to or reasonably ascertainable by the 
submitter.
    (6) The submitter has asserted confidentiality claims and has 
failed to:
    (i) Submit a second copy of the submission with all confidential 
information deleted for the public file, as required by 
Sec. 725.80(b)(2).
    (ii) Comply with the substantiation requirements as described in 
Sec. 725.94.
    (7) The submitter does not include any information required by 
section 5(b)(1) of the Act and pursuant to a rule promulgated under 
section 4 of the Act, as required by Sec. 725.25(f).
    (8) The submitter does not submit data which the submitter believes 
show that the microorganism will not present an unreasonable risk of 
injury to health or the environment, if EPA has listed the 
microorganism under section 5(b)(4) of the Act, as required in 
Sec. 725.25(g).
    (9) For MCANs, the submitter does not remit the fees required by 
Sec. 700.45(b)(1) or (b)(2)(vi) of this chapter.
    (b)(1) If EPA receives an incomplete submission under this part, 
the Director, or a designee, will notify the submitter within 30 days 
of receipt that the submission is incomplete and that the review period 
will not begin until EPA receives a complete submission.
    (2) If EPA obtains additional information during the review period 
for any submission that indicates the original submission was 
incomplete, the Director, or a designee, may declare the submission 
incomplete within 30 days after EPA obtains the additional information 
and so notify the submitter.
    (c) The notification that a submission is incomplete under 
paragraph (b) of this section will include:
    (1) A statement of the basis of EPA's determination that the 
submission is incomplete.
    (2) The requirements for correcting the incomplete submission.
    (3) Information on procedures under paragraph (d) of this section 
for filing objections to the determination or requesting modification 
of the requirements for completing the submission.
    (d) Within 10 days after receipt of notification by EPA that a 
submission is incomplete, the submitter may file written objections 
requesting that EPA accept the submission as complete or modify the 
requirements necessary to complete the submission.
    (e)(1) EPA will consider the objections filed by the submitter. The 
Director, or a designee, will determine whether the submission was 
complete or incomplete, or whether to modify the requirements for 
completing the submission. EPA will notify the submitter in writing of 
EPA's response within 10 days of receiving the objections.
    (2) If the Director, or a designee, determines, in response to the 
objection, that the submission was complete, the review period will be 
deemed suspended on the date EPA declared the submission incomplete, 
and will resume on the date that the submission is declared complete. 
The submitter need not correct the submission as EPA originally 
requested. If EPA can complete its review within the review period 
beginning on the date of the submission, the Director, or a designee, 
may inform the submitter that the running of the review period will 
resume on the date EPA originally declared it incomplete.
    (3) If the Director, or a designee, modifies the requirements for 
completing the submission or concurs with EPA's original determination, 
the review period will begin when EPA receives a complete submission.
    (f) Materially false or misleading statements. If EPA discovers at 
any time that a person submitted materially false or misleading 
statements in information submitted under this part, EPA may find that 
the submission was incomplete from the date it was submitted, and take 
any other appropriate action.


Sec. 725.36   New information.

    (a) During the review period, if a submitter possesses, controls, 
or knows of new information that materially adds to, changes, or 
otherwise makes significantly more complete the information included in 
the MCAN or exemption request, the submitter must send that information 
to the address listed in Sec. 725.25(c) within 10 days of receiving the 
new information, but no later than 5 days before the end of the review 
period.
    (b) The new submission must clearly identify the submitter, the 
MCAN or exemption request to which the new information is related, and 
the number assigned to that submission by EPA, if known to the 
submitter.
    (c) If the new information becomes available during the last 5 days 
of the review period, the submitter must immediately inform the EPA 
contact for that submission by telephone of the new information.


Sec. 725.40   Notice in the Federal Register.

    (a) Filing of Federal Register notice. After EPA receives a MCAN or 
an exemption request under this part, EPA will issue a notice in the 
Federal Register including the information specified in paragraph (b) 
of this section.
    (b) Contents of notice. (1) In the public interest, the specific 
microorganism identity listed in the submission will be published in 
the Federal Register unless the submitter has claimed the microorganism 
identity confidential. If the submitter claims confidentiality, a 
generic name will be published in accordance with Sec. 725.85.
    (2) The categories of use of the microorganism will be published as 
reported in the submission unless this information is claimed 
confidential. If confidentiality is claimed, the generic information 
which is submitted under Sec. 725.88 will be published.
    (3) A list of information submitted in accordance with 
Sec. 725.160(a), 725.255, 725.260, 725.355, or 725.455, as appropriate, 
will be published.
    (4) The submitter's identity will be published, unless the 
submitter has claimed it confidential.
    (c) Publication of exemption decisions. Following the expiration of 
the appropriate review period for the exemption request, EPA will issue 
a notice in the Federal Register indicating whether the request has 
been approved or denied and the reasons for the decision.


Sec. 725.50   EPA review.

     (a) MCANs. The review period specified in section 5(a) of the Act 
for MCANs runs for 90 days from the date the Document Control Officer 
receives a complete submission, or the date EPA determines the 
submission is complete under Sec. 725.33, unless the Agency extends the 
review period under section 5(c) of TSCA and Sec. 725.56.
    (b) Exemption requests. The review period starts on the date the 
Document Control Officer receives a complete exemption request, or the 
date EPA determines the request is complete under Sec. 725.33, unless 
the Agency extends the review period under Sec. 725.56. The review 
periods for exemption requests run as follows:
    (1) TERAs. The review period for TERAs is 60 days.
    (2) TMEs. The review period for TMEs is 45 days.
    (3) Tier II exemption requests. The review period for Tier II 
exemption requests is 45 days.


Sec. 725.54   Suspension of the review period.

    (a) A submitter may voluntarily suspend the running of the review 
period if the Director, or a designee, agrees. If the Director does not 
agree, the review period will continue to run, and EPA will notify the 
submitter. A submitter may request a suspension at any time during the 
review period. The suspension must be for a specified period of time.
    (b) A request for suspension may be made in writing to the address 
listed in Sec. 725.25(c). The suspension also may be made orally, 
including by telephone, to the submitter's EPA contact for that 
submission. EPA will send the submitter a written confirmation that the 
suspension has been granted.
    (1) An oral request may be granted for no longer than 15 days. To 
obtain a longer suspension, the Document Control Officer for the Office 
of Pollution Prevention and Toxics must receive written confirmation of 
the oral request. The review period is suspended as of the date of the 
oral request.
    (2) If the submitter has not made a previous oral request, the 
running of the review period is suspended as of the date of receipt of 
the written request by the Document Control Officer for the Office of 
Pollution Prevention and Toxics.


Sec. 725.56   Extension of the review period.

    (a) At any time during the review period, EPA may unilaterally 
determine that good cause exists to extend the review period specified 
for MCANs, or the exemption requests.
    (b) If EPA makes such a determination, EPA:
    (1) Will notify the submitter that EPA is extending the review 
period for a specified length of time and state the reasons for the 
extension.
    (2) For MCANS, may issue a notice for publication in the Federal 
Register which states that EPA is extending the review period and gives 
the reasons for the extension.
    (c) The total period of the extension may be for a period of up to 
the same length of time as specified for each type of submission in 
Sec. 725.50. If the initial extension is for less than the total time 
allowed, EPA may make additional extensions. However, the sum of the 
extensions may not exceed the total allowed.
    (d) The following are examples of situations in which EPA may find 
that good cause exists for extending the review period:
    (1) EPA has reviewed the submission and is seeking additional 
information.
    (2) EPA has received significant additional information during the 
review period.
    (3) The submitter has failed to correct a submission after 
receiving EPA's request under Sec. 725.32.
    (4) EPA has reviewed the submission and determined that there is a 
significant possibility that the microorganism will be regulated under 
section 5(e) or section 5(f) of the Act, but EPA is unable to initiate 
regulatory action within the initial review period.


Sec. 725.60   Withdrawal of submission by the submitter.

    (a) A submitter may withdraw a submission during the review period. 
A statement of withdrawal must be made in writing to the address listed 
in Sec. 725.25(c). The withdrawal is effective upon receipt of the 
statement by the Document Control Officer.
    (b) If a manufacturer or importer who withdrew a submission later 
resubmits a submission for the same microorganism, a new review period 
begins.


Sec. 725.65   Recordkeeping.

    (a) General provisions. (1) Any person who files under this part 
must retain documentation of information in the submission, including 
(i) any data in the submitter's possession or control; and (ii) records 
of production volume for the first 3 years of manufacture, import, or 
processing.
    (2) Any person who files under this part must retain documentation 
of the date of commencement of testing, manufacture, import, or 
processing.
    (3) Any person who is exempt from some or all of the reporting 
requirements of this part must retain documentation that supports the 
exemption.
    (4) All information required by this section must be retained for 3 
years from the date of commencement of each activity for which records 
are required under this part.
    (b) Specific requirements. In addition to the requirements of 
paragraph (a) of this section, specific recordkeeping requirements 
included in certain subparts must also be followed.
    (1) Additional recordkeeping requirements for activities conducted 
inside a structure are set forth in Sec. 725.235(h).
    (2) Additional recordkeeping requirements for TERAs are set forth 
in Sec. 725.250(f).
    (3) Additional recordkeeping requirements for TMEs are set forth in 
Sec. 725.350(c).
    (4) Additional recordkeeping requirements for Tier I exemptions 
under subpart G of this part are set forth in Sec. 725.424(a)(5).
    (5) Additional recordkeeping requirements for Tier II exemptions 
under subpart G of this part are set forth in Sec. 725.450(d).
    (6) Additional recordkeeping requirements for significant new uses 
of microorganisms reported under subpart L of this part are set forth 
in Sec. 725.850. Recordkeeping requirements may also be included when a 
microorganism and significant new use are added to subpart M of this 
part.


Sec. 725.67   Applications to exempt new microorganisms from this part.

    (a) Submission. (1) Any manufacturer or importer of a new 
microorganism may request, under TSCA section 5(h)(4), an exemption, in 
whole or in part, from this part by sending a Letter of Application to 
the Director, Chemical Control Division, Office of Pollution Prevention 
and Toxics, U.S. Environmental Protection Agency, 401 M St., SW., 
Washington, DC 20460.
    (2) The Letter of Application should provide information to show 
that any activities affected by the requested exemption will not 
present an unreasonable risk of injury to health or the environment. 
This information should include data described in the following 
paragraphs.
    (i) The effects of the new microorganism on health and the 
environment.
    (ii) The magnitude of exposure of human beings and the environment 
to the new microorganism.
    (iii) The benefits of the new microorganism for various uses and 
the availability of substitutes for such uses.
     (iv) The reasonably ascertainable economic consequences of 
granting or denying the exemption, including effects on the national 
economy, small business, and technological innovation.
     (b) Processing of the Letter of Application by EPA--(1) Grant of 
the Application. If, after consideration of the Letter of Application 
and any other relevant information available to the Agency, the 
Assistant Administrator for Prevention, Pesticides and Toxic Substances 
makes a preliminary determination that the new microorganism will not 
present an unreasonable risk of injury to health or the environment, 
the Assistant Administrator will propose a rule to grant the exemption 
using the applicable procedures in part 750 of this chapter.
    (2) Denial of the application. If the Assistant Administrator 
decides that the preliminary determination described in paragraph 
(b)(1) of this section cannot be made, the application will be denied 
by sending the applicant a written statement with the Assistant 
Administrator's reasons for denial.
    (c) Processing of the exemption--(1) Unreasonable risk standard. 
Granting a TSCA section 5(h)(4) exemption requires a determination that 
there will be no unreasonable risk.
    (i) An unreasonable risk determination under TSCA is an 
administrative judgment that requires balancing of the harm to health 
or the environment that a chemical substance may cause and the 
magnitude and severity of that harm, against the social and economic 
effects on society of Agency action to reduce that harm.
    (ii) A determination of unreasonable risk under TSCA section 
5(h)(4) will examine the reasonably ascertainable economic and social 
consequences of granting or denying the exemption after consideration 
of the effect on the national economy, small business, technological 
innovation, the environment, and public health.
    (2) Grant of the exemption. The exemption will be granted if the 
Assistant Administrator determines, after consideration of all relevant 
evidence presented in the rulemaking proceeding described in paragraph 
(b)(1) of this section, that the new microorganism will not present an 
unreasonable risk of injury to health or the environment.
    (3) Denial of the exemption. The exemption will be denied if the 
Assistant Administrator determines, after consideration of all relevant 
evidence presented in the rulemaking proceeding described in paragraph 
(b)(1) of this section, that the determination described in paragraph 
(c)(2) of this section cannot be made. A final decision terminating the 
rulemaking proceeding will be published in the Federal Register.


Sec. 725.70   Compliance.

    (a) Failure to comply with any provision of this part is a 
violation of section 15 of the Act (15 U.S.C. 2614).
    (b) A person who manufactures or imports a microorganism before a 
MCAN is submitted and the MCAN review period expires is in violation of 
section 15 of the Act even if that person was not required to submit 
the MCAN under Sec. 725.105.
    (c) Using a microorganism which a person knew or had reason to know 
was manufactured, processed, or distributed in commerce in violation of 
section 5 of the Act or this part is a violation of section 15 of the 
Act (15 U.S.C. 2614).
    (d) Failure or refusal to establish and maintain records or to 
permit access to or copying of records, as required by the Act, is a 
violation of section 15 of the Act (15 U.S.C. 2614).
    (e) Failure or refusal to permit entry or inspection as required by 
section 11 of the Act is a violation of section 15 of the Act (15 
U.S.C. 2614).
    (f) Violators may be subject to the civil and criminal penalties in 
section 16 of the Act (15 U.S.C. 2615) for each violation. Persons who 
submit materially misleading or false information in connection with 
the requirements of any provision of this part may be subject to 
penalties calculated as if they never filed their submissions.
    (g) EPA may seek to enjoin the manufacture or processing of a 
microorganism in violation of this part or act to seize any 
microorganism manufactured or processed in violation of this part or 
take other actions under the authority of section 7 of the Act (15 
U.S.C. 2606) or section 17 of the Act (15 U.S.C. 2616).


Sec. 725.75   Inspections.

    EPA will conduct inspections under section 11 of the Act to assure 
compliance with section 5 of the Act and this part, to verify that 
information required by EPA under this part is true and correct, and to 
audit data submitted to EPA under this part.
Subpart C--Confidentiality and Public Access to Information


Sec. 725.80  General provisions for confidentiality claims.

    (a) A person may assert a claim of confidentiality for any 
information submitted to EPA under this part.
    (1) Any person who asserts a claim of confidentiality for portions 
of the specific microorganism identity must provide the information as 
described in Sec. 725.85.
    (2) Any person who asserts a claim of confidentiality for a use of 
a microorganism must provide the information as described in 
Sec. 725.88.
    (3) Any person who asserts a claim of confidentiality for 
information contained in a health and safety study of a microorganism 
must provide the information described in Sec. 725.92.
    (b) Any claim of confidentiality must accompany the information 
when it is submitted to EPA.
    (1) When a person submits any information under this part, 
including any attachments, the claim(s) must be asserted by circling 
the specific information which is claimed as confidential and marking 
the page on which that information appears with an appropriate 
designation such as ``trade secret,'' ``TSCA CBI,'' or ``confidential 
business information.''
    (2) If any information is claimed confidential, the person must 
submit two copies of the information.
    (i) One copy of the information must be complete. In that copy, the 
submitter must mark the information which is claimed as confidential in 
the manner prescribed in paragraph (b)(1) of this section.
    (ii) The second copy must be complete except that all information 
claimed as confidential in the first copy must be deleted. EPA will 
place the second copy in the public file.
    (iii) If the submitter does not provide the second copy, the 
submission is incomplete and the review period does not begin to run 
until EPA receives the second copy, in accordance with Sec. 725.33.
    (iv) Any information contained within the copy submitted under 
paragraph (b)(2)(ii) of this section which has been in the public file 
for more than 30 days will be presumed to be in the public domain, 
notwithstanding any assertion of confidentiality made under this 
section.
    (c) Any person asserting a claim of confidentiality under this part 
must substantiate each claim in accordance with the requirements in 
Sec. 725.94.
    (d) EPA will disclose information that is subject to a claim of 
confidentiality asserted under this section only to the extent 
permitted by the Act, this subpart, and part 2 of this title.
    (e) If a submitter does not assert a claim of confidentiality for 
information at the time it is submitted to EPA, EPA may make the 
information public and place it in the public file without further 
notice to the submitter.


Sec. 725.85  Microorganism identity.

    (a) Claims applicable to the period prior to commencement of 
manufacture or import for general commercial use--(1) When to make a 
claim. (i) A person who submits information to EPA under this part may 
assert a claim of confidentiality for portions of the specific 
microorganism identity at the time of submission of the information. 
This claim will apply only to the period prior to the commencement of 
manufacture or import for general commercial use.
    (ii) A person who submits information to EPA under this part must 
reassert a claim of confidentiality and substantiate the claim each 
time the information is submitted to EPA. If a person claims certain 
information confidential in a TERA submission and wishes the same 
information to remain confidential in a subsequent TERA or MCAN 
submission, the person must reassert and resubstantiate the claim in 
the subsequent submission.
    (2) Assertion of claim. (i) A submitter may assert a claim of 
confidentiality only if the submitter believes that public disclosure 
prior to commencement of manufacture or import for general commercial 
use of the fact that anyone is initiating research and development 
activities pertaining to the specific microorganism or intends to 
manufacture or import the specific microorganism for general commercial 
use would reveal confidential business information. Claims must be 
substantiated in accordance with the requirements of Sec. 725.94(a).
    (ii) If the submission includes a health and safety study 
concerning the microorganism and if the claim for confidentiality with 
respect to the specific identity is denied in accordance with 
Sec. 725.92(c), EPA will deny a claim asserted under paragraph (a) of 
this section.
    (3) Development of generic name. Any person who asserts a claim of 
confidentiality for portions of the specific microorganism identity 
under this paragraph must provide one of the following items at the 
time the submission is filed:
    (i) The generic name which was accepted by EPA in the prenotice 
consultation conducted under paragraph (a)(4) of this section.
    (ii) One generic name that is only as generic as necessary to 
protect the confidential identity of the particular microorganism. The 
name should reveal the specific identity to the maximum extent 
possible. The generic name will be subject to EPA review and approval.
    (4) Determination by EPA. (i) Any person who intends to assert a 
claim of confidentiality for the specific identity of a new 
microorganism may seek a determination by EPA of an appropriate generic 
name for the microorganism before filing a submission. For this 
purpose, the person should submit to EPA:
    (A) The specific identity of the microorganism.
    (B) A proposed generic name(s) which is only as generic as 
necessary to protect the confidential identity of the new 
microorganism. The name(s) should reveal the specific identity of the 
microorganism to the maximum extent possible.
    (ii) Within 30 days, EPA will inform the submitter either that one 
of the proposed generic names is adequate or that none is adequate and 
further consultation is necessary.
    (5) Use of generic name. If a submitter claims microorganism 
identity as confidential under paragraph (a) of this section, and if 
the submitter complies with paragraph (a)(2) of this section, EPA will 
issue for publication in the Federal Register notice described in 
Sec. 725.40 the generic name proposed by the submitter or one agreed 
upon by EPA and the submitter.
    (b) Claims applicable to the period after commencement of 
manufacture or import for general commercial use--(1) Maintaining 
claim. Any claim of confidentiality under paragraph (a) of this section 
is applicable only until the microorganism is manufactured or imported 
for general commercial use and becomes eligible for inclusion on the 
Inventory. To maintain the confidential status of the microorganism 
identity when the microorganism is added to the Inventory, a submitter 
must reassert the confidentiality claim and substantiate the claim in 
the notice of commencement of manufacture required under Sec. 725.190.
    (i) A submitter may not claim the microorganism identity 
confidential for the period after commencement of manufacture or import 
for general commercial use unless the submitter claimed the 
microorganism identity confidential under paragraph (a) of this section 
in the MCAN submitted for the microorganism.
    (ii) A submitter may claim the microorganism identity confidential 
for the period after commencement of manufacture or import for general 
commercial use if the submitter did not claim the microorganism 
identity confidential under paragraph (a) of this section in any TERA 
submitted for the microorganism, but subsequently did claim 
microorganism identity confidential in the MCAN submitted for the 
microorganism.
    (2) Assertion of claim. (i) A person who believes that public 
disclosure of the fact that anyone manufactures or imports the 
microorganism for general commercial use would reveal confidential 
business information may assert a claim of confidentiality under 
paragraph (b) of this section.
    (ii) If the notice includes a health and safety study concerning 
the new microorganism, and if the claim for confidentiality with 
respect to the microorganism identity is denied in accordance with 
Sec. 725.92(c), EPA will deny a claim asserted under paragraph (b) of 
this section.
    (3) Requirements for assertion. Any person who asserts a 
confidentiality claim for microorganism identity must:
    (i) Comply with the requirements of paragraph (a)(3) of this 
section regarding submission of a generic name.
    (ii) Agree that EPA may disclose to a person with a bona fide 
intent to manufacture or import the microorganism the fact that the 
particular microorganism is included on the confidential Inventory for 
purposes of notification under section 5(a)(1)(A) of the Act.
    (iii) Have available and agree to furnish to EPA upon request the 
taxonomic designations and supplemental information required by 
Sec. 725.12.
    (iv) Provide a detailed written substantiation of the claim, in 
accordance with the requirements of Sec. 725.94(b).
    (4) Denial of claim. If the submitter does not meet the 
requirements of paragraph (b) of this section, EPA will deny the claim 
of confidentiality.
    (5) Acceptance of claim. (i) EPA will publish a generic name on the 
public Inventory if:
    (A) The submitter asserts a claim of confidentiality in accordance 
with this paragraph.
    (B) No claim for confidentiality of the microorganism identity as 
part of a health and safety study has been denied in accordance with 
part 2 of this title or Sec. 725.92.
    (ii) Publication of a generic name on the public Inventory does not 
create a category for purposes of the Inventory. Any person who has a 
bona fide intent to manufacture or import a microorganism which is 
described by a generic name on the public Inventory may submit an 
inquiry to EPA under Sec. 725.15(b) to determine whether the particular 
microorganism is included on the confidential Inventory.
    (iii) Upon receipt of a request described in Sec. 725.15(b), EPA 
may require the submitter who originally asserted confidentiality for a 
microorganism to submit to EPA the information listed in paragraph 
(b)(3)(iii) of this section.
    (iv) Failure to submit any of the information required under 
paragraph (b)(3)(iii) of this section within 10 calendar days of 
receipt of a request by EPA under paragraph (b) of this section will 
constitute a waiver of the original submitter's confidentiality claim. 
In this event, EPA may place the specific microorganism identity on the 
public Inventory without further notice to the original submitter.
    (6) Use of generic name on the public Inventory. If a submitter 
asserts a claim of confidentiality under paragraph (b) of this section, 
EPA will examine the generic microorganism name proposed by the 
submitter.
    (i) If EPA determines that the generic name proposed by the 
submitter is only as generic as necessary to protect the confidential 
identity of the particular microorganism, EPA will place that generic 
name on the public Inventory.
    (ii) If EPA determines that the generic name proposed by the 
submitter is more generic than necessary to protect the confidential 
identity, EPA will propose in writing, for review by the submitter, an 
alternative generic name that will reveal the identity of the 
microorganism to the maximum extent possible.
    (iii) If the generic name proposed by EPA is acceptable to the 
submitter, EPA will place that generic name on the public Inventory.
    (iv) If the generic name proposed by EPA is not acceptable to the 
submitter, the submitter must explain in detail why disclosure of that 
generic name would reveal confidential business information and propose 
another generic name which is only as generic as necessary to protect 
the confidential identity of the microorganism. If EPA does not receive 
a response from the submitter within 30 days after the submitter 
receives the proposed name, EPA will place EPA's chosen generic name on 
the public Inventory. If the submitter does provide the information 
requested, EPA will review the response. If the submitter's proposed 
generic name is acceptable, EPA will publish that generic name on the 
public Inventory. If the submitter's proposed generic name is not 
acceptable, EPA will notify the submitter of EPA's choice of a generic 
name. Thirty days after this notification, EPA will place the chosen 
generic name on the public Inventory.


Sec. 725.88   Uses of a microorganism.

    (a) Assertion of claim. A person who submits information to EPA 
under this part on the categories or proposed categories of use of a 
microorganism may assert a claim of confidentiality for this 
information.
    (b) Requirements for claim. A submitter that asserts such a claim 
must:
    (1) Report the categories or proposed categories of use of the 
microorganism.
    (2) Provide, in nonconfidential form, a description of the uses 
that is only as generic as necessary to protect the confidential 
business information. The generic use description will be included in 
the Federal Register notice described in Sec. 725.40.
    (c) Generic use description. The person must submit the information 
required by paragraph (b) of this section by describing the uses as 
precisely as possible, without revealing the information which is 
claimed confidential, to disclose as much as possible how the use may 
result in human exposure to the microorganism or its release to the 
environment.


Sec. 725.92   Data from health and safety studies of microorganisms.

    (a) Information other than specific microorganism identity. Except 
as provided in paragraph (b) of this section, EPA will deny any claim 
of confidentiality with respect to information included in a health and 
safety study of a microorganism, unless the information would disclose 
confidential business information concerning:
    (1) Processes used in the manufacture or processing of a 
microorganism.
    (2) Information which is not in any way related to the effects of a 
microorganism on human health or the environment, such as, the name of 
the submitting company, cost or other financial data, product 
development or marketing plans, and advertising plans, for which the 
person submits a claim of confidentiality in accordance with 
Sec. 725.80.
    (b) Microorganism identity--(1) Claims applicable to the period 
prior to commencement of manufacture or import for general commercial 
use. A claim of confidentiality for the period prior to commencement of 
manufacture or import for general commercial use for the specific 
identity of a microorganism for which a health and safety study was 
submitted must be asserted in conjunction with a claim asserted under 
Sec. 725.85(a). The submitter must substantiate each claim in 
accordance with the requirements of Sec. 725.94(a).
    (2) Claims applicable to the period after commencement of 
manufacture or import for general commercial use. To maintain the 
confidential status of the specific identity of a microorganism for 
which a health and safety study was submitted after commencement of 
manufacture or import for general commercial use, the claim must be 
reasserted and substantiated in conjunction with a claim under 
Sec. 725.85(b). The submitter must substantiate each claim in 
accordance with the requirements of Sec. 725.94(b).
    (c) Denial of confidentiality claim. EPA will deny a claim of 
confidentiality for microorganism identity under paragraph (b) of this 
section, unless:
    (1) The information would disclose processes used in the 
manufacture or processing of a microorganism.
    (2) The microorganism identity is not necessary to interpret a 
health and safety study.
    (d) Use of generic names. When EPA discloses a health and safety 
study containing a microorganism identity, which the submitter has 
claimed confidential, and if the Agency has not denied the claim under 
paragraph (c) of this section, EPA will identify the microorganism by 
the generic name selected under Sec. 725.85.


Sec. 725.94   Substantiation requirements.

    (a) Claims applicable to the period prior to commencement of 
manufacture or import for general commercial use--(1) MCAN, TME, Tier I 
certification, and Tier II exemption request requirements. Any person 
who submits a MCAN, TME, Tier I certification, or Tier II exemption 
request should strictly limit confidentiality claims to that 
information which is confidential and proprietary to the business.
    (i) If any information in the submission is claimed as confidential 
business information, the submitter must substantiate each claim by 
submitting written answers to the questions in paragraphs (c), (d), and 
(e) of this section at the time the person submits the information.
    (ii) If the submitter does not provide written substantiation as 
required in paragraph (a)(1)(i) of this section, the submission will be 
considered incomplete and the review period will not begin in 
accordance with Sec. 725.33.
    (2) TERA requirements. Any person who submits a TERA, should 
strictly limit confidentiality claims to that information which is 
confidential and proprietary to the business.
    (i) If any information in such a submission is claimed as 
confidential business information, the submitter must substantiate each 
of those claims by submitting written answers to the questions in 
paragraphs (d) and (e) of this section at the time the person submits 
the information.
    (ii) If the submitter does not provide written substantiation as 
required in paragraph (a)(2)(i) of this section, the submission will be 
considered incomplete and the TERA review period will not begin.
    (b) Claims applicable to the period after commencement of 
manufacture or import for general commercial use. (1) If a submitter 
claimed portions of the microorganism identity confidential in the MCAN 
and wants the identity to be listed on the confidential Inventory, the 
claim must be reasserted and substantiated at the time the Notice of 
Commencement (NOC) is submitted. Otherwise, EPA will list the specific 
microorganism identity on the public Inventory.
    (2) The submitter must substantiate the claim for confidentiality 
of the microorganism identity by answering all of the questions in 
paragraphs (c), (d), and (e) in this section. In addition, the 
following questions must be answered:
    (i) What harmful effects to the company or institution's 
competitive position, if any, would result if EPA publishes on the 
Inventory the identity of the microorganism? How could a competitor use 
such information given the fact that the identity of the microorganism 
otherwise would appear on the TSCA Inventory with no link between the 
microorganism and the company or industry? How substantial would the 
harmful effects of disclosure be? What is the causal relationship 
between the disclosure and the harmful effects?
    (ii) Has the identity of the microorganism been kept confidential 
to the extent that competitors do not know it is being manufactured or 
imported for general commercial use by anyone?
    (c) General questions. The following questions must be answered in 
detail for each confidentiality claim:
    (1) For what period of time is a claim of confidentiality being 
asserted? If the claim is to extend until a certain event or point in 
time, indicate that event or time period. Explain why the information 
should remain confidential until such point.
    (2) Briefly describe any physical or procedural restrictions within 
the company or institution relating to the use and storage of the 
information claimed as confidential. What other steps, if any, apply to 
use or further disclosure of the information?
    (3) Has the information claimed as confidential been disclosed to 
individuals outside of the company or institution? Will it be disclosed 
to such persons in the future? If so, what restrictions, if any, apply 
to use or further disclosure of the information?
    (4) Does the information claimed as confidential appear, or is it 
referred to, in any of the following:
    (i) Advertising or promotional materials for the microorganism or 
the resulting end product.
    (ii) Material safety data sheets or other similar materials for the 
microorganism or the resulting end product.
    (iii) Professional or trade publications.
    (iv) Any other media available to the public or to your 
competitors.
    (v) Patents.
    (vi) Local, State, or Federal agency public files.
If the answer is yes to any of these questions, indicate where the 
information appears and explain why it should nonetheless be treated as 
confidential.
    (5) Has EPA, another Federal agency, a Federal court, or a State 
made any confidentiality determination regarding the information 
claimed as confidential? If so, provide copies of such determinations.
    (6) For each type of information claimed confidential, describe the 
harm to the company or institution's competitive position that would 
result if this information were disclosed. Why would this harm be 
substantial? How could a competitor use such information? What is the 
causal connection between the disclosure and harm?
    (7) If EPA disclosed to the public the information claimed as 
confidential, how difficult would it be for the competitor to enter the 
market for the resulting product? Consider such constraints as capital 
and marketing cost, specialized technical expertise, or unusual 
processes.
    (d) Microorganism identity and production method. If 
confidentiality claims are asserted for the identity of the 
microorganism or information on how the microorganism is produced, the 
following questions must be answered:
    (1) Has the microorganism or method of production been patented in 
the U.S. or elsewhere? If so, why is confidentiality necessary?
    (2) Does the microorganism leave the site of production or testing 
in a form which is accessible to the public or to competitors? What is 
the cost to a competitor, in time and money, to develop appropriate use 
conditions? What factors facilitate or impede product analysis?
    (3) For each additional type of information claimed as 
confidential, explain what harm would result from disclosure of each 
type of information if the identity of the microorganism were to remain 
confidential.
    (e) Health and safety studies of microorganisms. If confidentiality 
claims are asserted for information in a health or safety study of a 
microorganism, the following questions must be answered:
    (1) Would the disclosure of the information claimed confidential 
reveal: (i) Confidential process information, or (ii) information 
unrelated to the effects of the microorganism on human health and the 
environment. Describe the causal connection between the disclosure and 
harm.
    (2) Does the company or institution assert that disclosure of the 
microorganism identity is not necessary to interpret any health and 
safety studies which have been submitted? If so, explain how a less 
specific identity would be sufficient to interpret the studies.


Sec. 725.95   Public file.

    All information submitted, including any health and safety study of 
a microorganism and other supporting documentation, will become part of 
the public file for that submission, unless such materials are claimed 
confidential. In addition, EPA may add materials to the public file, 
unless such materials are claimed confidential. Any of the 
nonconfidential material described in this subpart will be available 
for public inspection in the TSCA Public Docket Office, Rm. NE-B607, 
401 M St., SW., Washington, DC, between the hours of 8 a.m. and noon 
and 1 p.m. to 4 p.m., Monday through Friday, excluding legal holidays.
Subpart D--Microbial Commercial Activities Notification Requirements


Sec. 725.100   Scope and purpose.

    (a) This subpart establishes procedures for submission of a notice 
to EPA under section 5(a) of TSCA for persons who manufacture, import, 
or process microorganisms for commercial purposes. This notice is 
called a Microbial Commercial Activity Notice (MCAN). It is expected 
that MCANs will in general only be submitted for microorganisms 
intended for general commercial use.
    (b) Persons subject to MCAN submission are described in 
Sec. 725.105.
    (c) Exclusions and exemptions specific to MCAN submissions are 
described in Sec. 725.110.
    (d) Submission requirements applicable specifically to MCANs are 
described at Sec. 725.150.
    (e) Data requirements for MCANs are set forth in Sec. Sec. 725.155 
and 725.160.
    (f) EPA review procedures specific to MCANs are set forth in 
Sec. 725.170.
    (g) Subparts A through C of this part apply to any MCAN submitted 
under this subpart.


Sec. 725.105   Persons who must report.

    (a) Manufacturers of new microorganisms. (1) MCAN submission is 
required for any person who intends to manufacture for general 
commercial use in the United States a new microorganism. Exclusions are 
described in Sec. 725.110.
    (2) If a person contracts with a manufacturer to produce or process 
a new microorganism and (i) The manufacturer produces or processes the 
microorganism exclusively for that person, and (ii) that person 
specifies the identity of the microorganism, and controls the total 
amount produced and the basic technology for the plant process, then 
that person must submit the MCAN. If it is unclear who must report, EPA 
should be contacted to determine who must submit the MCAN.
    (3) Only manufacturers that are incorporated, licensed, or doing 
business in the United States may submit a MCAN.
    (b) Importers of new microorganisms. (1) MCAN submission is 
required for a person who intends to import into the United States for 
general commercial use a new microorganism. Exclusions are described in 
Sec. 725.110.
    (2) When several persons are involved in an import transaction, the 
MCAN must be submitted by the principal importer. If no one person fits 
the principal importer definition in a particular transaction, the 
importer should contact EPA to determine who must submit the MCAN for 
that transaction.
    (3) Except as otherwise provided in paragraph (b)(4) of this 
section, the provisions of this subpart D apply to each person who 
submits a MCAN for a new microorganism which such person intends to 
import for a general commercial use. In addition, each importer must 
comply with paragraph (b)(4) of this section.
    (4) EPA will hold the principal importer, or the importer that EPA 
determines must submit the MCAN when there is no principal importer 
under paragraph (b)(2) of this section, liable for complying with this 
part, for completing the MCAN, and for the completeness and 
truthfulness of all information which it submits.
    (c) Manufacturers, importers, or processors of microorganisms who 
intend to use or distribute the microorganism for a significant new 
use. MCAN submission is required for any person who intends to 
manufacture, import, or process for commercial purposes a microorganism 
identified as having one or more significant new uses in subpart M of 
this part, and who intends either to engage in a significant new use of 
the microorganism or intends to distribute it in commerce. Persons 
excluded from reporting on significant new uses of microorganisms and 
additional procedures for reporting are described in subpart L of this 
part.


Sec. 725.110   Persons not subject to this subpart.

    Persons are not subject to the requirements of this subpart for the 
following activities:
    (a) Manufacturing, importing, or processing solely for research and 
development microorganisms that meet the requirements for an exemption 
under subpart E of this part.
    (b) Manufacturing, importing, or processing microorganisms for test 
marketing activities which have been granted an exemption under subpart 
F of this part.
    (c) Manufacturing or importing microorganisms under the conditions 
of a Tier I or Tier II exemption under subpart G of this part.


Sec. 725.150   Procedural requirements for this subpart.

    General requirements for all MCANs under this part are contained in 
Sec. 725.25. In addition, the following requirements apply to MCANs 
submitted under this subpart:
    (a) When to submit a MCAN. A MCAN must be submitted at least 90 
calendar days prior to manufacturing or importing a new microorganism 
and at least 90 calendar days prior to manufacturing, importing, or 
processing a microorganism for a significant new use.
    (b) Section 5(b) of TSCA. The submitter must comply with any 
applicable requirement of section 5(b) of TSCA.
    (c) Contents of a MCAN. Each person who submits a MCAN under this 
subpart must provide the information and test data described in 
Sec. Sec. 725.155 and 725.160.
    (d) Recordkeeping. Each person who submits a MCAN under this 
subpart must comply with the recordkeeping requirements of Sec. 725.65.


Sec. 725.155   Information to be included in the MCAN.

    (a) Each person who is required by this part to submit a MCAN must 
provide EPA in writing with all information known to or reasonably 
ascertainable by the person that would permit EPA to make a reasoned 
evaluation of the human health and environmental effects of the 
microorganism, or any microbial mixture or article, including 
information on its effects on humans, animals, plants, and other 
microorganisms, and in the environment. However, no person is required 
to include information which relates solely to exposure of humans or 
ecological populations outside of the United States. The information to 
be submitted under this subpart includes, but is not limited to, the 
information listed in paragraphs (c) through (h) of this section. All 
information submitted must be true and correct.
    (b) When specific information is not submitted, an explanation of 
why such information is not available or not applicable must be 
included.
    (c) Submitter identification. (1) The name and headquarters address 
of the submitter.
    (2) The name, address, and office telephone number (including area 
code) of the principal technical contact representing the submitter.
    (d) Microorganism identity information. Persons must submit 
sufficient information to allow the microorganism to be accurately and 
unambiguously identified for listing purposes as required by 
Sec. 725.12.
    (1) Description of the recipient microorganism(s) and the new 
microorganism. (i) Data substantiating the taxonomy of the recipient 
microorganism(s) and the new microorganism(s) to the level of strain, 
as appropriate. In lieu of data, EPA will accept a letter from a 
culture collection substantiating taxonomy, provided EPA, upon request 
to the submitter, may have access to the data supporting the taxonomic 
designation.
    (ii) Information on the morphological and physiological features of 
the new microorganism(s).
    (iii) Other specific data by which the new microorganism(s) may be 
uniquely identified for Inventory purposes.
    (2) Genetic construction of the new microorganism(s). (i) Data 
substantiating the taxonomy of the donor organism(s). In lieu of data, 
EPA will accept a letter from a culture collection substantiating 
taxonomy, provided EPA, upon request to the submitter, may have access 
to the data supporting the taxonomic designation.
    (ii) Description of the traits for which the new microorganism(s) 
has been selected or developed and other traits known to have been 
added or modified.
    (iii) A detailed description of the genetic construction of the new 
microorganism, including the technique used to modify the microorganism 
(e.g., fusion of cells, injection of DNA, electroporation or chemical 
poration, or methods used for induced mutation and selection). The 
description should include, for example, function of the introduced 
genetic material, including any changes predicted to alter function; 
how the introduced genetic material is expected to affect behavior; 
expression, alteration, and stability of the introduced genetic 
material; methods for vector construction and introduction; and a 
description of the regulatory and structural genes that are components 
of the introduced genetic material, including genetic maps of the 
introduced sequences.
    (3) Phenotypic and ecological characteristics. (i) Habitat, 
geographical distribution, and source of the recipient 
microorganism(s).
    (ii) Survival and dissemination under relevant environmental 
conditions including a description of methods for detecting the 
microorganism(s) in the environment and the sensitivity limit of 
detection for these techniques.
    (iii) A description of anticipated biological interactions with and 
effects on target organisms and other organisms such as competitors, 
prey, hosts, symbionts, parasites, and pathogens; a description of host 
range; a description of pathogenicity, infectivity, toxicity, 
virulence, or action as a vector of pathogens; and capacity for genetic 
transfer under laboratory and relevant environmental conditions.
    (iv) A description of anticipated involvement in biogeochemical or 
biological cycling processes, involvement in rate limiting steps in 
mineral or nutrient cycling, or involvement in inorganic compounds 
cycling (such as possible sequestration or transformation of heavy 
metals).
    (e) Byproducts. A description of the byproducts resulting from the 
manufacture, processing, use, and disposal of the new microorganism(s).
    (f) Total production volume. The estimated maximum amount of the 
new microorganism(s) intended to be manufactured or imported during the 
first year of production and the estimated maximum amount to be 
manufactured or imported during any consecutive 12-month period during 
the first 3 years of production. This estimate may be by weight or 
volume and should include an estimation of viability (i.e., viable 
cells per unit volume or colony forming units per unit dry weight).
    (g) Use information. A description of intended categories of use by 
function and application, the estimated percent of production volume 
devoted to each category of use, and the percent of the new 
microorganism(s) in the formulation for each commercial or consumer 
use.
    (h) Worker exposure and environmental release. (1) For sites 
controlled by the submitter:
    (i) The identity of sites where the new microorganism(s) will be 
manufactured, processed, or used. For purposes of this section, the 
site for a person who imports a new microorganism is the site of the 
operating unit within the person's organization which is directly 
responsible for importing the new microorganism and which controls the 
import transaction. The import site may in some cases be the 
organization's headquarters office in the United States.
    (ii) A process description of each manufacture, processing, and use 
operation, which includes a diagram of the major unit operations and 
conversions, the identity and entry point of all feedstocks, and the 
identity of any possible points of release of the new microorganism 
from the process, including a description of all controls, including 
engineering controls, used to prevent such releases.
    (iii) Worker exposure information, including worker activities, 
physical form of process streams which contain the new microorganism to 
which workers may be exposed, the number of workers, and the duration 
of activities.
    (iv) Information on release of the new microorganism to the 
environment, including the quantity and media of release and type of 
control technology used.
    (v) A narrative description of the intended transport of the new 
microorganism, including the means of transport, containment methods to 
be used during transport, and emergency containment procedures to be 
followed in case of accidental release.
    (vi) Procedures for disposal of any articles, waste, clothing, or 
other equipment involved in the activity, including procedures for 
inactivation of the new microorganism, containment, disinfection, and 
disposal of contaminated items.
    (2) For sites not controlled by the submitter, a description of 
each type of processing and use operation involving the new 
microorganism, including identification of the estimated number of 
processing or use sites, situations in which worker exposure to and/or 
environmental release of the new microorganism will occur, the number 
of workers exposed and the duration of exposure; procedures for 
transport of the new microorganism and for disposal, including 
procedures for inactivation of the new microorganism; and control 
measures which limit worker exposure and environmental release.


Sec. 725.160   Submission of health and environmental effects data.

    (a) Test data on the new microorganism in the possession or control 
of the submitter. (1) Except as provided in Sec. 725.25(h), and in 
addition to the information required by Sec. 725.155(d)(3), each MCAN 
must contain all test data in the submitter's possession or control 
which are related to the effects on health or the environment of any 
manufacture, processing, distribution in commerce, use, or disposal of 
the new microorganism or any microbial mixture or article containing 
the new microorganism, or any combination of such activities. This 
includes test data concerning the new microorganism in a pure culture 
or formulated form as used in one of the activities listed above.
    (2) A full report or standard literature citation must be submitted 
for the following types of test data:
    (i) Health effects data.
    (ii) Ecological effects data.
    (iii) Physical and chemical properties data.
    (iv) Environmental fate characteristics.
    (v) Monitoring data and other test data related to human exposure 
to or environmental release of the new microorganism.
    (3)(i) If the data do not appear in the open scientific literature, 
the submitter must provide a full report. A full report includes the 
experimental methods and materials, results, discussion and data 
analysis, conclusions, references, and the name and address of the 
laboratory that developed the data.
    (ii) If the data appear in the open scientific literature, the 
submitter need only provide a standard literature citation. A standard 
literature citation includes author, title, periodical name, date of 
publication, volume, and page numbers.
    (4)(i) If a study, report, or test is incomplete when a person 
submits a MCAN, the submitter must identify the nature and purpose of 
the study; name and address of the laboratory developing the data; 
progress to date; types of data collected, significant preliminary 
results; and anticipated completion date.
    (ii) If a test or experiment is completed before the MCAN review 
period ends, the person must submit the study, report, or test to the 
address listed in Sec. 725.25(c), as specified in paragraph (a)(3)(i) 
of this section, within 10 days of receiving it, but no later than 5 
days before the end of the review period. If the test or experiment is 
completed during the last 5 days of the review period, the submitter 
must immediately inform its EPA contact for that submission by 
telephone.
    (5) For test data in the submitter's possession or control which 
are not listed in paragraph (a)(2) of this section, a person is not 
required to submit a complete report. The person must submit a summary 
of the data. If EPA so requests, the person must submit a full report 
within 10 days of the request, but no later than 5 days before the end 
of the review period.
    (6) All test data described under paragraph (a) of this section are 
subject to these requirements, regardless of their age, quality, or 
results.
    (b) Other data concerning the health and environmental effects of 
the new microorganism that are known to or reasonably ascertainable by 
the submitter. (1) Except as provided in Sec. 725.25(h), and in 
addition to the information required by Sec. 725.155(c)(3), any person 
who submits a MCAN must describe the following data, including any data 
from a health and safety study of a microorganism, if the data are 
related to effects on health or the environment of any manufacture, 
processing, distribution in commerce, use, or disposal of the 
microorganism, of any microbial mixture or article containing the new 
microorganism, or of any combination of such activities:
    (i) Any data, other than test data, in the submitter's possession 
or control.
    (ii) Any data, including test data, which are not in the 
submitter's possession or control, but which are known to or reasonably 
ascertainable by the submitter. For the purposes of this section, data 
are known to or reasonably ascertainable by the submitter if the data 
are known to any of its employees or other agents who are associated 
with the research and development, test marketing, or commercial 
marketing of the microorganism.
    (2) Data that must be described include data concerning the new 
microorganism in a pure culture or formulated form as used in one of 
the activities listed in paragraph (b)(1) of this section.
    (3) The description of data reported under paragraph (b) of this 
section must include:
    (i) If the data appear in the open scientific literature, a 
standard literature citation, which includes the author, title, 
periodical name, date of publication, volume, and pages.
    (ii) If the data are not available in the open scientific 
literature, a description of the type of data and summary of the 
results, if available, and the names and addresses of persons the 
submitter believes may have possession or control of the data.
    (4) All data described by paragraph (b) of this section are subject 
to these requirements, regardless of their age, quality, or results; 
and regardless of whether they are complete at the time the MCAN is 
submitted.


Sec. 725.170   EPA review of the MCAN.

    General procedures for review of all submissions under this part 
are contained in Sec. Sec. 725.28 through 725.60. In addition, the 
following procedures apply to EPA review of MCANs submitted under this 
subpart:
    (a) Length of the review period. The MCAN review period specified 
in section 5(a) of the Act runs for 90 days from the date the Document 
Control Officer for the Office of Pollution Prevention and Toxics 
receives a complete MCAN, or the date EPA determines the MCAN is 
complete under Sec. 725.33, unless the Agency extends the period under 
section 5(c) of the Act and Sec. 725.56.
    (b) Notice of expiration of MCAN review period. (1) EPA will notify 
the submitter that the MCAN review period has expired or that EPA has 
completed its review of the MCAN. Expiration of the review period does 
not constitute EPA approval or certification of the new microorganism, 
and does not mean that EPA may not take regulatory action against the 
microorganism in the future.
    (2) After expiration of the MCAN review period, in the absence of 
regulatory action by EPA under section 5(e), 5(f), or 6(a) of the Act, 
the submitter may manufacture or import the microorganism even if the 
submitter has not received notice of expiration.
    (3) Early notification that EPA has completed its review does not 
permit commencement of manufacture or import prior to the expiration of 
the 90-day MCAN review period.
    (c) Any person submitting a MCAN in response to the requirements of 
this subpart shall not manufacture, import, or process a microorganism 
subject to this subpart until the review period, including all 
extensions and suspensions, has expired.


Sec. 725.190   Notice of commencement of manufacture or import.

    (a) Applicability. Any person who commences the manufacture or 
import of a new microorganism for nonexempt, general commercial use for 
which that person previously submitted a section 5(a) notice under this 
part must submit a notice of commencement (NOC) of manufacture or 
import.
    (b) When to report. (1) If manufacture or import for nonexempt, 
general commercial use begins on or after [insert date 44 days after 
date of publication in the Federal Register of the final rule], the 
submitter must submit the NOC to EPA no later than 30 calendar days 
after the first day of such manufacture or import.
    (2) If manufacture or import for nonexempt, general commercial use 
began or will begin before [insert date 44 days after date of 
publication in the Federal Register of the final rule], the submitter 
must submit the NOC by [insert date 44 days after date of publication 
in the Federal Register of the final rule].
    (3) Submission of an NOC prior to the commencement of manufacture 
or import is a violation of TSCA section 15.
    (c) Information to be reported. The NOC must contain the following 
information: Specific microorganism identity, MCAN number, and the date 
when manufacture or import commences. If the person claimed 
microorganism identity confidential in the MCAN, and wants the identity 
to be listed on the confidential Inventory, the claim must be 
reasserted and resubstantiated in accordance with Sec. 725.85(b). 
Otherwise, EPA will list the specific microorganism identity on the 
public Inventory.
    (d) Where to submit. NOCs should be submitted to the address listed 
in Sec. 725.25(c).
Subpart E--Exemptions for Research and Development Activities


Sec. 725.200   Scope and purpose.

    (a) This subpart describes exemptions from the reporting 
requirements under subpart D of this part for research and development 
activities involving microorganisms.
    (b) In lieu of complying with subpart D of this part, persons 
described in Sec. 725.205 may submit a TSCA Experimental Release 
Application (TERA) for research and development activities involving 
microorganisms.
    (c) Exemptions from part 725 are provided at Sec. Sec. 725.232, 
725.234, and 725.238.
    (d) Submission requirements specific for TERAs are described at 
Sec. 725.250.
    (e) Data requirements for TERAs are set forth in Sec. Sec. 725.255 
and 725.260.
    (f) EPA review procedures specific for TERAs are set forth in 
Sec. Sec. 725.270 and 725.288.
    (g) Subparts A through C of this part apply to any submission under 
this subpart.


Sec. 725.205   Persons who may report under this subpart.

    (a) Certain research and development activities involving 
microorganisms subject to TSCA jurisdiction are exempt from reporting 
under this part. A person conducting research and development 
activities which do not meet the conditions for the exemptions 
described in Sec. 725.232, 725.234, or 725.238 may report under this 
subpart.
    (b) A person may report under this subpart for the following 
research and development activities:
    (1) A person who intends to manufacture or import for commercial 
purposes a new microorganism.
    (2) A person who intends to manufacture, import, or process for 
commercial purposes a microorganism identified in subpart M of this 
part as a significant new use. Additional reporting requirements for 
significant new uses are described in subpart L of this part.


Sec. 725.232   Activities subject to the jurisdiction of other Federal 
programs or agencies.

    This part does not apply to any research and development activity 
that meets all of the following conditions.
    (a) Meets the requirements of Sec. 725.234(a) and (c).
    (b) Is receiving research funds from another Federal agency which 
controls the research in accordance with applicable portions of the NIH 
``Guidelines for Research Involving Recombinant DNA Molecules.'' This 
control may be exercised through direct regulatory authority or through 
requiring compliance with the NIH Guidelines as a condition of 
receiving funds.


Sec. 725.234   Activities conducted inside a structure.

     A person who manufactures, imports, or processes a microorganism 
is not subject to the reporting requirements under subpart D of this 
part if all of the following conditions are met:
    (a) The microorganism is manufactured, imported, or processed 
solely for research and development activities.
    (b) The microorganism is used by, or directly under the supervision 
of, a technically qualified individual, as defined in Sec. 725.3. The 
technically qualified individual must maintain documentation of the 
procedures selected to comply with paragraph (d) of this section and 
must ensure that the procedures are used.
    (c) There is no intentional testing of a microorganism outside of a 
structure, as structure is defined in Sec. 725.3.
    (d) Containment and/or inactivation controls. (1) Selection and use 
of containment and/or inactivation controls inside a structure for a 
particular microorganism shall take into account the following:
    (i) Factors relevant to the organism's ability to survive in the 
environment.
    (ii) Potential routes of release in air, solids and liquids; in or 
on waste materials and equipment; in or on people, including 
maintenance and custodial personnel; and in or on other organisms, such 
as insects and rodents.
    (iii) Procedures for transfer of materials between facilities.
    (2) The TQI's selection of containment and/or inactivation controls 
shall be approved and certified by an authorized official (other than 
the TQI) of the institution that is conducting the test prior to the 
commencement of the test.
    (3) Records shall be developed and maintained describing the 
selection and use of the containment and/or inactivation controls, 
including contingency plans for emergency clean-up or test termination, 
that will be used during the test. These records, which must be 
maintained at the location where the research and development activity 
is being conducted, shall be submitted to the Agency at the Agency's 
written request and within the time frame specified in the Agency's 
request.
    (4) Subsequent to Agency review of records in accordance with 
paragraph (d)(3) of this section, changes to the containment/
inactivation controls selected under paragraph (d)(1) of this section 
must be made upon Agency order. Failure to comply with the Agency's 
order shall result in automatic loss of eligibility for an exemption 
under this section.
    (e) The manufacturer, importer, or processor notifies all persons 
in its employ or to whom it directly distributes the microorganism, who 
are engaged in experimentation, research, or analysis on the 
microorganism, including the manufacture, processing, use, transport, 
storage, and disposal of the microorganism associated with research and 
development activities, of any risk to health, identified under 
Sec. 725.235(a), which may be associated with the microorganism. The 
notification must be made in accordance with Sec. 725.235(b).


Sec. 725.235   Conditions of exemption for activities conducted inside 
a structure.

    (a) Determination of risks. (1) To determine whether notification 
under Sec. 725.234(e) is required, the manufacturer, importer, or 
processor must review and evaluate the following information to 
determine whether there is reason to believe there is any risk to 
health which may be associated with the microorganism:
    (i) Information in its possession or control concerning any 
significant adverse reaction of persons exposed to the microorganism 
which may reasonably be associated with such exposure.
    (ii) Information provided to the manufacturer, importer, or 
processor by a supplier or any other person concerning a health risk 
believed to be associated with the microorganism.
    (iii) Health and environmental effects data in its possession or 
control concerning the microorganism.
    (iv) Information on health effects which accompanies any EPA rule 
or order issued under section 4, 5, or 6 of the Act that applies to the 
microorganism and of which the manufacturer, importer, or processor has 
knowledge.
    (2) When the research and development activity is conducted solely 
inside a laboratory and exposure to the microorganism is controlled 
through the implementation of prudent practices for handling 
microorganisms of unknown human health or environmental effects and any 
distribution, except for purposes of disposal, is to other such 
laboratories for further research and development activity, the 
information specified in paragraph (a)(1) of this section need not be 
reviewed and evaluated. (For purposes of this paragraph (a)(2), a 
laboratory is defined as a contained research facility, where 
relatively small quantities of microorganisms are used on a non-
production basis, and where activities involve the use of containers 
for reactions, transfers, and other handling of microorganisms designed 
to be easily manipulated by a single individual.)
    (b) Notification to employees. (1) The manufacturer, importer, or 
processor must notify the persons identified in Sec. 725.234(e) by 
means of a container labeling system, conspicuous placement of notices 
in areas where exposure may occur, written notification to each person 
potentially exposed, or any other method of notification which 
adequately informs persons of health risks which the manufacturer, 
importer, or processor has reason to believe may be associated with the 
microorganism, as determined under paragraph (a)(1) of this section.
    (2) If the manufacturer, importer, or processor distributes a 
microorganism manufactured, imported, or processed under this section 
to persons not in its employ, the manufacturer, importer, or processor 
must in written form:
    (i) Notify those persons that the microorganism is to be used only 
for research and development purposes.
    (ii) Provide the notice of health risks specified in paragraph 
(b)(1) of this section.
    (3) The adequacy of any notification under this section is the 
responsibility of the manufacturer, importer, or processor.
    (c) No applicability to general commercial use. A microorganism is 
not exempt from reporting under subpart D of this part if any amount of 
the microorganism, including as part of a mixture, is processed, 
distributed in commerce, or used, for any commercial purpose other than 
research and development, except where the microorganism is processed, 
distributed in commerce, or used only as an impurity or as part of an 
article.
     (d) Waste disposal. Quantities of the inactivated microorganism, 
or mixtures or articles containing the inactivated microorganism, 
remaining after completion of research and development activities may 
be disposed of as a waste in accordance with applicable Federal, State, 
and local regulations.
    (e) Impurities and articles. Quantities of research and development 
microorganisms existing solely as impurities in a product or 
incorporated into an article, in accordance with paragraph (c) of this 
section, are not subject to the requirements of Sec. 725.234 and 
paragraphs (a) and (b) of this section, once research and development 
activities have been completed.
    (f) Pesticide uses. A person who manufactures, imports, or 
processes a microorganism solely for research and development is not 
required to comply with the requirements of this section if the 
person's exclusive intention is to perform research and development 
activities solely for the purpose of determining whether the 
microorganism can be used as a pesticide.
    (g) Recordkeeping. A person who manufactures, imports, or processes 
a microorganism under this section must retain the following records:
    (1) Records describing selection and use of containment and/or 
inactivation controls required by Sec. 725.234(d)(3) and certification 
by an authorized official required by Sec. 725.234(d)(2) for each 
microorganism.
    (2) Copies or citations to information reviewed and evaluated under 
paragraph (a)(1) of this section to determine the need to make any 
notification of risk.
    (3) Documentation of prudent laboratory practices used instead of 
notification and evaluation under paragraph (a)(2) of this section.
    (4) Documentation of the nature and method of notification under 
paragraph (b)(1) of this section, including copies of any labels or 
written notices used.
    (5) The names and addresses of any persons other than the 
manufacturer, importer, or processor to whom the substance is 
distributed, the identity of the microorganism, the amount distributed, 
and copies of the notifications required under paragraph (b)(2) of this 
section.


Sec. 725.238   Activities conducted outside a structure.

    (a) Exemption. (1) Research and development activities involving 
intentional testing in the environment of certain microorganisms listed 
in Sec. 725.239 may be conducted without prior review by EPA if all of 
the conditions of this section and Sec. 725.239 are met.
    (2) The research and development activity involving a microorganism 
listed in Sec. 725.239 must be conducted by, or directly under the 
supervision of, a technically qualified individual, as defined in 
Sec. 725.3.
    (b) Certification. To be eligible for the exemption under this 
section, a manufacturer or importer must submit to EPA prior to 
initiation of the activity a document signed by an authorized official 
containing the following information:
    (1) Name, address, and phone number of the manufacturer or 
importer.
    (2) Location, estimated duration, and planned start date of the 
test.
    (3) Certification of the following:
    (i) Compliance with the conditions of the exemption specified for 
the microorganism in Sec. 725.239.
    (ii) Notification of the appropriate Federal and state authorities 
of the planned test.
    (c) Recordkeeping. Persons who conduct research and development 
activities under this section must comply with the recordkeeping 
requirements of Sec. 725.65 and retain documentation that supports 
their compliance with the requirements of this section and the specific 
requirements for the microorganism listed in Sec. 725.239.


Sec. 725.239   Use of specific microorganisms in activities conducted 
outside a structure.

    (a) Bradyrhizobium japonicum. To qualify for an exemption under 
this section, all of the following conditions must be met for a test 
involving Bradyrhizobium japonicum:
    (1) Characteristics of recipient microorganism. The recipient 
microorganism is limited to strains of Bradyrhizobium japonicum.
    (2) Modification of traits. (i) The introduced genetic material 
must meet the criteria for poorly mobilizable listed in 
Sec. 725.421(c).
    (ii) The introduced genetic material must consist only of the 
following components:
    (A) The structural gene(s) of interest, which have the following 
limitations:
    (1) For antibiotic resistance, the structural gene may originate 
from any source.
    (2) For traits other than antibiotic resistance, the structural 
gene must be limited to the genera Bradyrhizobium and Rhizobium.
    (B) The regulatory sequences permitting the expression of solely 
the gene(s) of interest.
    (C) Associated nucleotide sequences needed to move genetic 
material, including linkers, homopolymers, adaptors, transposons, 
insertion sequences, and restriction enzyme sites.
    (D) The vector nucleotide sequences needed for vector transfer.
    (E) The vector nucleotide sequences needed for vector maintenance.
    (3) Limitations on exposure. (i) The test site area must be no more 
than 5 terrestrial acres.
    (ii) The technically qualified individual must select appropriate 
methods to limit the dissemination of modified Bradyrhizobium 
japonicum.
    (b) Rhizobium meliloti. To qualify for an exemption under this 
section, all of the following conditions must be met for a test 
involving Rhizobium meliloti:
    (1) Characteristics of recipient microorganism. The recipient 
microorganism is limited to strains of Rhizobium meliloti.
    (2) Modification of traits. (i) The introduced genetic material 
must meet the criteria for poorly mobilizable listed in Sec. 725.421(c) 
of this part.
    (ii) The introduced genetic material must consist only of the 
following components:
    (A) The structural gene(s) of interest, which have the following 
limitations:
    (1) For antibiotic resistance, the structural gene may originate 
from any source.
    (2) For traits other than antibiotic resistance, the structural 
gene must be limited to the genera Bradyrhizobium and Rhizobium.
    (B) The regulatory sequences permitting the expression of solely 
the gene(s) of interest.
    (C) Associated nucleotide sequences needed to move genetic 
material, including linkers, homopolymers, adaptors, transposons, 
insertion sequences, and restriction enzyme sites.
    (D) The vector nucleotide sequences needed for vector transfer.
    (E) The vector nucleotide sequences needed for vector maintenance.
    (3) Limitations on exposure. (i) The test site area must be no more 
than 5 terrestrial acres.
    (ii) The technically qualified individual must select appropriate 
methods to limit the dissemination of modified Rhizobium meliloti.


Sec. 725.250   Procedural requirements for this subpart.

    General requirements for all submissions under this part are 
contained in Sec. 725.25. In addition, the following requirements apply 
to applications submitted under this subpart:
    (a) When to submit the TERA. Each person who is eligible to submit 
a TERA under this subpart must submit the TERA at least 60 calendar 
days prior to initiating the proposed research and development 
activity.
    (b) Contents of the TERA. Each person who submits a TERA under this 
subpart must provide the information and test data described in 
Sec. Sec. 725.255 and 725.260. In addition, the submitter must supply 
sufficient information to enable EPA to evaluate the effects of all 
activities for which approval is requested.
    (c) A person described under Sec. 725.205 may submit a TERA for one 
or more microorganisms and one or more research and development 
activities, including a research program.
    (d) EPA will either approve the TERA, with or without conditions, 
or disapprove it under procedures established in this subpart.
    (e) The manufacturer, importer, or processor who receives a TERA 
approval must comply with all terms of the approval and remains liable 
for compliance with all terms, regardless of who conducts the research 
and development activity. Any person conducting the research and 
development activity approved under the TERA must comply with all terms 
of the TERA approval.
    (f) Recordkeeping. Persons submitting a TERA must comply with the 
recordkeeping requirements of Sec. 725.65. In addition, the following 
requirements apply to TERAs:
    (1) Each person submitting a TERA under this part must retain 
documentation of information contained in the TERA for a period of 3 
years from the date that the results of the study are submitted to the 
Agency.
    (2) Summaries of all data, conclusions, and reports resulting from 
the conduct of the research and development activity under the TERA 
must be submitted to the EPA address identified in Sec. 725.25(c) 
within 1 year of the termination of the activity.


Sec. 725.255   Information to be included in the TERA.

    (a) To review a TERA, EPA must have sufficient information to 
permit a reasoned evaluation of the health and environmental effects of 
the planned test in the environment. The person seeking EPA approval 
must submit all information known to or reasonably ascertainable by the 
submitter on the microorganism and the research and development 
activity, including information not listed in paragraphs (c), (d), and 
(e) of this section that the person believes will be useful for EPA's 
risk assessment. The TERA must be in writing and must include at least 
the information described in the following paragraphs.
    (b) When specific information is not submitted, an explanation of 
why such information is not available or not applicable must be 
included.
    (c) Persons applying for a TERA, must include the submitter 
identification and microorganism identity information required for 
MCANs in Sec. 725.155(c), (d)(1), and (d)(2).
    (d) Persons applying for a TERA must submit phenotypic and 
ecological characteristics information required in Sec. 725.155(d)(3) 
as it relates directly to the conditions of the proposed research and 
development activity.
    (e) Persons applying for a TERA must also submit the following 
information about the proposed research and development activity:
    (1) A detailed description of the proposed research and development 
activity. (i) The objectives and significance of the activity and a 
rationale for testing the microorganisms in the environment.
    (ii) Number of cells released (including viability per volume if 
applicable) and the method(s) of application or release.
    (iii) Characteristics of the test site(s), including location, 
geographical, physical, chemical, and biological features, proximity to 
human habitation or activity, and description of site characteristics 
that would influence dispersal or confinement.
    (iv) Target organisms (if the microorganism(s) to be tested has an 
intended target), including identification of each target organism and 
anticipated mechanism and result of interaction.
    (v) Planned start date and duration of each activity.
    (vi) Evidence that State authorities have been notified.
    (2) Information on monitoring, confinement, mitigation, and 
emergency termination procedures. (i) Confinement procedures for the 
activity, access and security measures, and procedures for routine 
termination of the activity.
    (ii) Mitigation and emergency procedures.
    (iii) Measures to detect and control potential adverse effects.
    (iv) Name of principal investigator and chief of site personnel 
responsible for emergency procedures.
    (v) Personal protective equipment, engineering controls, and 
procedures to be followed to minimize dispersion of the 
microorganism(s) by people, machinery, or equipment.
    (vi) Procedures for disposal of any articles, waste, clothing, 
machinery, or other equipment involved in the experimental release, 
including methods for inactivation of the microorganism, containment, 
disinfection, and disposal of contaminated items.


Sec. 725.260   Submission of health and environmental effects data.

    Each TERA must contain all available data concerning actual or 
potential effects on human health or the environment of the new 
microorganism that are in the possession or control of the submitter 
and a description of other data known to or reasonably ascertainable by 
the submitter that will permit a reasoned evaluation of the planned 
test in the environment. The data must be reported in the manner 
described in Sec. 725.160(a)(3) and (b)(3).


Sec. 725.270   EPA review of the TERA.

    General procedures for review of all submissions under this part 
are contained in Sec. Sec. 725.28 through 725.60. In addition, the 
following procedures apply to EPA review of applications submitted 
under this subpart:
    (a) Length of the review period. (1) The review period for the TERA 
will be 60 days from the date the Document Control Officer for the 
Office of Pollution Prevention and Toxics receives a complete TERA, or 
the date EPA determines the TERA is complete under Sec. 725.33, unless 
EPA finds good cause for an extension under Sec. 725.56.
    (2) A submitter shall not proceed with the research and development 
activity described in the TERA unless and until EPA provides written 
approval of the TERA. A submitter may receive early approval if a 
review is completed in less than 60 days.
    (b) EPA decision regarding proposed TERA activity. (1) A decision 
concerning a TERA under this subpart will be made by the Administrator, 
or a designee.
    (2) If EPA determines that the proposed research and development 
activity for the microorganism does not present an unreasonable risk of 
injury to human health or the environment, EPA will notify the 
submitter that the TERA is approved and that the submitter can proceed 
with the proposed research and development activity described in the 
TERA.
    (3) EPA may include conditions in its approval of the TERA that 
would be stated in a TERA agreement under paragraph (c) of this 
section.
    (4) If EPA concludes that the proposed research and development 
activity may present an unreasonable risk of injury to human health or 
the environment, EPA will deny the TERA and will provide reasons for 
the denial in writing.
    (c) TERA agreement. (1) The TERA agreement is legally binding on 
the TERA submitter and the Agency. The TERA submitter agrees to be 
bound by the requirements set out in the agreement and also certifies 
that all data submitted to the Agency is true and correct.
    (2) If EPA approves a TERA, the submitter must conduct the research 
and development activity only as described in the TERA agreement and in 
accordance with any conditions set forth by EPA in its approval of the 
TERA agreement.
    (3) Any person who fails to comply with any requirement or 
condition of the TERA agreement shall be in violation of sections 5 and 
15 of TSCA and so subject to civil and criminal penalties under section 
16 of TSCA.


Sec. 725.288   Revocation or modification of TERA approval.

    (a) Significant questions about risk. (1) If, after approval of a 
TERA under this subpart, EPA receives information which raises 
significant questions about the Agency's determination that the 
activity does not present an unreasonable risk of injury to human 
health or the environment, EPA will notify the submitter in writing of 
those questions.
    (2) The submitter may, within 10 days of receipt of EPA's notice, 
provide in writing additional information or arguments concerning the 
significance of the questions and whether EPA should modify or revoke 
the approval of the TERA.
    (3) After considering any such information and arguments, EPA will 
decide whether to change its determination regarding approval of the 
TERA.
    (i) If EPA determines that it will continue to approve the TERA, it 
will notify the submitter in writing. In continuing to approve a TERA, 
EPA may prescribe additional conditions which must be followed by the 
submitter. In this case, EPA may reserve the right to review the test 
data and revoke the TERA approval after some time period.
    (ii) If EPA concludes that it can no longer approve the TERA, it 
will notify the submitter in writing and state its reasons. In that 
event, the submitter must terminate the research and development 
activity within 48 hours of receipt of the notice in accordance with 
directions provided by EPA in the notice.
    (b) Evidence of unreasonable risk. (1) If, after approval of a TERA 
under this subpart, EPA receives information which indicates that the 
proposed research and development activity will present an unreasonable 
risk of injury to human health or the environment, EPA will notify the 
submitter in writing and state its reasons.
    (2) The submitter must provide additional safeguards or terminate 
the research and development activity in accordance with directions 
provided by EPA in the notice.
    (3) The submitter may then submit additional information or 
arguments concerning the matters raised by EPA and whether EPA should 
modify or revoke the approval of the TERA in accordance with paragraph 
(a)(2) of this section.
    (4) EPA will consider the information and arguments under paragraph 
(a)(3) of this section.
    (5) The submitter may resume the activity only upon written notice 
from EPA that EPA has approved resumption of the activity. In approving 
resumption of an activity, EPA may prescribe additional conditions 
which must be followed by the submitter.
    (c) Modifications. If, after approval of a TERA under this subpart, 
the submitter concludes that it is necessary to alter the conduct of 
the research and development activity in a manner which would result in 
the activity being different from that described in the TERA agreement 
and any conditions EPA prescribed in its approval, the submitter must 
inform the EPA contact for the TERA and may not modify the activity 
without the approval of EPA.
Subpart F--Exemptions for Test Marketing


Sec. 725.300   Scope and purpose.

    (a) This subpart describes exemptions from the reporting 
requirements under subpart D of this part for test marketing activities 
involving microorganisms.
    (b) In lieu of complying with subpart D of this part, persons 
described in Sec. 725.305 may submit an application for a test 
marketing exemption (TME).
    (c) Submission requirements specific for TME applications are 
described at Sec. 725.350.
    (d) Data requirements for TME applications are set forth in 
Sec. 725.355.
    (e) EPA review procedures specific for TMEs are set forth in 
Sec. 725.370.
    (f) Subparts A through C of this part apply to any submission under 
this subpart.


Sec. 725.305   Persons who may report under this subpart.

    A person identified in this section may apply for a test marketing 
exemption. EPA may grant the exemption if the person demonstrates that 
the microorganism will not present an unreasonable risk of injury to 
health or the environment as a result of the test marketing. A person 
may report under this subpart for the following test marketing 
activities:
    (a) A person who intends to manufacture or import for commercial 
purposes a new microorganism.
    (b) A person who intends to manufacture, import, or process for 
commercial purposes a microorganism identified in subpart M of this 
part as a significant new use.


Sec. 725.350   Procedural requirements for this subpart.

    General requirements for all submissions under this part are 
contained in Sec. 725.25. In addition, the following requirements apply 
to applications submitted under this subpart:
    (a) Prenotice consultation. EPA strongly suggests that for a TME, 
the submitter contact the Agency for a prenotice consultation regarding 
eligibility for a TME.
    (b) When to submit a TME. Each manufacturer or importer who is 
eligible to submit a TME under this subpart must submit the TME at 
least 45 calendar days before commencing the test marketing activity.
    (c) Recordkeeping. Each person who is granted a TME must comply 
with the recordkeeping requirements of Sec. 725.65. In addition, any 
person who obtains a TME must retain documentation of compliance with 
any restrictions imposed by EPA when it grants the TME. This 
information must be retained for 3 years from the final date of 
manufacture or import under the exemption.


Sec. 725.355   Information to be included in the TME application.

    (a) To review a TME application, EPA must have sufficient 
information to permit a reasoned evaluation of the health and 
environmental effects of the planned test marketing activity. The 
person seeking EPA approval must submit all information known to or 
reasonably ascertainable by the submitter on the microorganism and the 
test marketing activity, including information not listed in paragraphs 
(c), (d), and (e) of this section that the person believes will 
demonstrate that the microorganism will not present an unreasonable 
risk of injury to health or the environment as a result of the test 
marketing. The TME application must be in writing and must include at 
least the information described in paragraphs (b), (c), (d), and (e) of 
this section.
    (b) When specific information is not submitted, an explanation of 
why such information is not available or not applicable must be 
included.
    (c) Persons applying for a TME must submit the submitter 
identification and microorganism identity information required for 
MCANs in Sec. 725.155(c), (d)(1), and (d)(2).
    (d) Persons applying for a TME must submit phenotypic and 
ecological characteristics information required in Sec. 725.155(d)(3) 
as it relates directly to the conditions of the proposed test marketing 
activity.
    (e) Persons applying for a TME must also submit the following 
information about the proposed test marketing activity:
    (1) Proposed test marketing activity. (i) The maximum quantity of 
the microorganism which the applicant will manufacture or import for 
test marketing.
    (ii) The maximum number of persons who may be provided the 
microorganism during test marketing.
    (iii) The maximum number of persons who may be exposed to the 
microorganism as a result of test marketing, including information 
regarding duration and route of such exposures.
    (iv) A description of the test marketing activity, including its 
duration and how it can be distinguished from full-scale commercial 
production and research and development activities.
    (2) Health and environmental effects data. All existing data 
regarding health and environmental effects of the microorganism must be 
reported in accordance with Sec. 725.160.


Sec. 725.370   EPA review of the TME application.

    General procedures for review of all submissions under this part 
are contained in Sec. Sec. 725.28 through 725.60. In addition, the 
following procedures apply to EPA review of TME applications submitted 
under this subpart:
    (a) No later than 45 days after EPA receives a TME, the Agency will 
either approve or deny the application.
    (b) A submitter may only proceed with test marketing activities 
after receipt of EPA approval.
    (c) In approving a TME application, EPA may impose any restrictions 
necessary to ensure that the microorganism will not present an 
unreasonable risk of injury to health and the environment as a result 
of test marketing.
Subpart G--Exemption for Microorganisms in General Commercial Use


Sec. 725.400   Scope and purpose.

    (a) This subpart describes exemptions from reporting under subpart 
D of this part, and from review under this part altogether, for 
manufacturing and importing of certain new microorganisms for general 
commercial use.
    (b) Recipient microorganisms eligible for the tiered exemption from 
review under this part are listed in Sec. 725.420.
    (c) Criteria for the introduced genetic material contained in the 
new microorganisms are described in Sec. 725.421.
    (d) Physical containment and control technologies are described in 
Sec. 725.422.
    (e) The conditions for the Tier I exemption are listed in 
Sec. 725.424.
    (f) In lieu of complying with subpart D of this part, persons using 
recipient microorganisms eligible for the tiered exemption may submit a 
Tier II exemption request. The limited reporting requirements for the 
Tier II exemption, including data requirements, are described in 
Sec. Sec. 725.450 and 725.455.
    (g) EPA review procedures for the Tier II exemption are set forth 
in Sec. 725.470.
    (h) Subparts A through C of this part apply to any submission under 
this subpart.


Sec. 725.420   Recipient microorganisms.

    The following recipient microorganisms are eligible for either 
exemption under this part:
    (a) Acetobacter aceti.
    (b) Aspergillus niger.
    (c) Aspergillus oryzae.
    (d) Bacillus licheniformis.
    (e) Bacillus subtilis.
    (f) Clostridium acetobutylicum.
    (g) Escherichia coli K-12.
    (h)  Penicillium roqueforti.
    (i) Saccharomyces cerevisiae.
    (j) Saccharomyces uvarum.


Sec. 725.421   Introduced genetic material.

    For a new microorganism to qualify for either exemption under this 
subpart, introduced genetic material must meet all of the criteria 
listed in this section.
    (a) Limited in size. The introduced genetic material must consist 
only of the following:
    (1) The structural gene(s) of interest.
    (2) The regulatory sequences permitting the expression of solely 
the gene(s) of interest.
    (3) Associated nucleotide sequences needed to move genetic 
material, including linkers, homopolymers, adaptors, transposons, 
insertion sequences, and restriction enzyme sites.
    (4) The nucleotide sequences needed for vector transfer.
    (5) The nucleotide sequences needed for vector maintenance.
    (b) Well characterized. For introduced genetic material, well 
characterized means that the following have been determined:
    (1) The function of all of the products expressed from the 
structural gene(s).
    (2) The function of sequences that participate in the regulation of 
expression of the structural gene(s).
    (3) The presence or absence of associated nucleotide sequences.
    (c) Poorly mobilizable. The ability of the introduced genetic 
material to be transferred and mobilized is inactivated, with a 
resulting frequency of transfer of less than 10-8 transfer events 
per recipient.
    (d) Free of certain sequences. The introduced genetic material must 
not contain any part of the nucleotide sequences that encode the toxins 
described in this paragraph (d). Although these toxins are listed 
according to the source organism, it is use of the nucleotide sequences 
that encode the toxins that are being restricted and not the use of the 
source organisms. The source organisms are listed to provide 
specificity in identification of sequences whose use is restricted. 
Similar or identical sequences may be isolated from organisms other 
than those listed below. Comparable toxin sequences, regardless of the 
organism from which they are derived, must not be included in the 
introduced genetic material. Toxin synonyms are included in 
parentheses.
    (1) Sequences for protein synthesis inhibitor. 

                                                                        
          Sequence Source                         Toxin Name            
                                                                        
Corynebacterium diphtheriae & C.     Diphtheria toxin                   
 ulcerans                                                               
Pseudomonas aeruginosa               Exotoxin A                         
Shigella dysenteriae                 Shigella toxin (Shiga toxin,       
                                      Shigella dysenteriae type I toxin,
                                      Vero cell toxin)                  
Abrus precatorius, seeds             Abrin                              
Ricinus communis, seeds              Ricin                              
                                                                        

    (2) Sequences for neurotoxins. 

                                                                        
          Sequence Source                         Toxin Name            
                                                                        
Clostridium botulinum                Neurotoxins A, B, C1, D, E, F, G   
                                      (Botulinum toxins, botulinal      
                                      toxins)                           
Clostridium tetani                   Tetanus toxin (tetanospasmin)      
Proteus mirabilis                    Neurotoxin                         
Staphylococcus aureus                Alpha toxin (alpha lysin)          
Yersinia pestis                      Murine toxin                       
                                                                        
  Snake toxins                       ...................................
Bungarus caeruleus                   Caeruleotoxin                      
Bungarus multicinctus                Beta-bungarotoxin (phospholipase)  
Crotalus spp.                        Crotoxin (phospholipase)           
Dendroaspis viridis                  Neurotoxin                         
Naja naja varieties                  Neurotoxin                         
Notechia scutatus                    Notexin (phospholipase)            
Oxyuranus scutellatus                Taipoxin                           
                                                                        
  Invertebrate toxins                                                   
Chironex fleckeri                    Neurotoxin                         
Androctnus australis                 Neurotoxin                         
Centruroides sculpturatus            Neurotoxin                         
                                                                        

    (3) Sequences for oxygen labile cytolysins. 

                                                                        
          Sequence Source                         Toxin Name            
                                                                        
Bacillus alve                        Alveolysin                         
Bacillus cereus                      Cereolysin                         
Bacillus laterosporus                Laterosporolysin                   
Bacillus thuringiensis               Thuringiolysin                     
Clostridium bifermentans             Lysin                              
Clostridium botulinum                Lysin                              
Clostridium caproicum                Lysin                              
Clostridium chauvoei                 Delta-toxin                        
Clostridium histolyticum             Epsilon-toxin                      
Clostridium novyi                    Gamma-toxin                        
Clostridium oedematiens              Delta-toxin                        
Clostridium perfringens              Theta-toxin (Perfringolysin)       
Clostridium septicum                 Delta-toxin                        
Clostridium sordellii                Lysin                              
Clostridium tetani                   Tetanolysin                        
Listeria monocytogenes               Listeriolysin (A B)                
Streptococcus pneumoniae             Pneumolysin                        
Streptococcus pyogene                Streptolysin O (SLO)               
                                                                        

    (4) Sequences for toxins affecting membrane function.

                                                                        
          Sequence Source                         Toxin Name            
                                                                        
 Bacillus anthracis                  Edema factor (Factors I II); Lethal
                                      factor (Factors II III)           
Bacillus cereus                      Enterotoxin (diarrheagenic toxin,  
                                      mouse lethal factor)              
Bordetella pertussis                 Adenylate cyclase (Heat-labile     
                                      factor); Pertussigen (pertussis   
                                      toxin, islet activating factor,   
                                      histamine sensitizing factor,     
                                      lymphocytosis promoting factor)   
Clostridium botulinum                C2 toxin                           
Clostridium difficile                Enterotoxin (toxin A)              
Clostridium perfringens              Beta-toxin; Delta-toxin            
Escherichia coli & other             Heat-labile enterotoxins (LT); Heat-
 Enterobacteriaceae spp.              stable enterotoxins (STa, ST1     
                                      subtypes ST1a ST1b; also STb,     
                                      STII)                             
Legionella pneumophila               Cytolysin                          
Vibrio cholerae & Vibrio mimicus     Cholera toxin (choleragen)         
                                                                        

    (5) Sequences that affect membrane integrity.

                                                                        
          Sequence Source                         Toxin Name            
                                                                        
Clostridium bifermentans & other     Lecithinase                        
 Clostridium spp                                                        
Clostridium perfringens              Alpha-toxin (phospholipase C,      
                                      lecithinase); Enterotoxin         
Corynebacterium pyogenes & other     Cytolysin (phospholipase C), Ovis  
 Corynebacterium spp.                 toxin (sphingomyelinase D)        
Staphylococcus aureus                Beta-lysin (beta toxin)            
                                                                        

    (6) Sequences that are general cytotoxins. 

                                                                        
          Sequence Source                         Toxin Name            
                                                                        
Adenia digitata                      Modeccin                           
Aeromonas hydrophila                 Aerolysin (beta-lysin, cytotoxic   
                                      lysin)                            
Clostridium difficile                Cytotoxin (toxin B)                
Clostridium perfringens              Beta-toxin; Epsilon-toxin; Kappa-  
                                      toxin                             
Escherichia coli & other             Cytotoxin (Shiga-like toxin, Vero  
 Enterobacteriaceae spp.              cell toxin)                       
Pseudomonas aeruginosa               Proteases                          
Staphylococcus aureus                Gamma lysin (Gamma toxin);         
                                      Enterotoxins (SEA, SEB, SEC, SED  
                                      SEE); Pyrogenic exotoxins A B;    
                                      Toxic shock syndrome toxins (TSST-
                                      1)                                
Staphylococcus aureus & Pseudomonas  Leucocidin (leukocidin, cytotoxin) 
 aeruginosa                                                             
Streptococcus pyogenes               Streptolysin S (SLS); Erythrogenic 
                                      toxins (scarlet fever toxins,     
                                      pyrogenic exotoxins)              
Yersinia enterocolitica              Heat-stable enterotoxins (ST)      
                                                                        

Sec. 725.422   Physical containment and control technologies.

    All of the following criteria for the physical containment and 
control technologies of the facility are required for a Tier I 
exemption and serve as guidance for a Tier II exemption:
    (a) The structure is designed and operated to contain the 
microorganisms.
    (b) Limit entry only to those persons whose presence is critical to 
the reliability or safety of the activity.
    (c) Provide written, published, and implemented procedures for the 
safety of personnel and control of hygiene.
    (d) Include inactivation procedures demonstrated and documented to 
be effective against the new microorganism contained in liquid and 
solid wastes prior to disposal of the wastes. The inactivation 
procedures must reduce microbial concentrations by at least 6 logs in 
liquid and solid wastes.
    (e) Provide and document effectiveness of features to reduce 
microbial concentration by at least 2 logs in aerosols and exhaust 
gases released from the structure.
    (f) Include and document systems for controlling dissemination of 
the microorganisms through other routes.
    (g) Have in place emergency clean-up procedures.


Sec. 725.424   Requirements for the Tier I exemption.

    (a) Conditions of exemption. The manufacture or import of a new 
microorganism for general commercial use is not subject to review under 
this part if all of the following conditions are met:
    (1) The recipient microorganism is listed and meets any 
requirements specified in Sec. 725.420.
    (2) The introduced genetic material meets the criteria under 
Sec. 725.421.
    (3) The physical containment and control technologies of any 
facility in which the microorganism will be used meet the criteria 
under Sec. 725.422.
    (4) The manufacturer or importer submits a certification described 
in paragraph (b) of this section to EPA 30 days before commencing 
initial manufacture or import.
    (5) The manufacturer or importer complies with the recordkeeping 
requirements of Sec. 725.65 and maintains records that verify 
compliance with the following:
    (i) The certifications made in paragraph (b) of this section.
    (ii) All the eligibility criteria for the Tier I exemption 
including the criteria for the recipient microorganism, the introduced 
genetic material, the physical containment and control technologies.
    (b) Certification. To be eligible for the exemption under this 
subpart, a manufacturer or importer must submit to EPA a document 
signed by a responsible company official containing the information 
listed in this paragraph.
    (1) Name and address of manufacturer or importer.
    (2) Date when manufacture or import is expected to begin.
    (3) Certification of the following:
    (i) The recipient microorganism is one of those listed in 
Sec. 725.420
    (ii) Compliance with the introduced genetic material criteria 
described in Sec. 725.421.
    (iii) Compliance with the containment requirements described in 
Sec. 725.422, including the provision in paragraph (a)(3) of this 
section.
    (4) The site of waste disposal and the type of permits for 
disposal, the permit numbers and the institutions issuing the permits.
    (5) The certification statement required in Sec. 725.25(b).


Sec. 725.426   Liability of the manufacturer or importer who uses the 
Tier I exemption.

    The Tier I exemption under Sec. 725.424 applies only to a 
manufacturer or importer of a new microorganism that certifies that the 
microorganism will be used in all cases in compliance with 
Sec. Sec. 725.420, 725.421, and 725.422.


Sec. 725.428   Requirements for the Tier II exemption.

    The manufacturer or importer of a new microorganism for general 
commercial use may submit to EPA a Tier II exemption request in lieu of 
a MCAN under subpart D of this part if all of the following conditions 
are met:
    (a) The recipient microorganism is listed and meets any 
requirements specified in Sec. 725.420.
    (b) The introduced genetic material meets the criteria under 
Sec. 725.421.
    (c) The criteria listed under Sec. 725.422 for physical containment 
and control technologies of facilities should be used as guidance to 
satisfy the Tier II exemption request data requirements listed at 
Sec. 725.455(d). EPA will review proposed process and containment 
procedures as part of the submission for a Tier II exemption under this 
section.


Sec. 725.450   Procedural requirements for the Tier II exemption.

    General requirements for all submissions under this part are 
contained in Sec. 725.25. In addition, the following requirements apply 
to requests submitted under this subpart:
    (a) Prenotice consultation. EPA strongly suggests that for a Tier 
II exemption, the submitter contact the Agency for a prenotice 
consultation regarding eligibility for expedited review.
    (b) When to submit the Tier II exemption request. Each manufacturer 
or importer who is eligible to submit a Tier II exemption request under 
this subpart must submit the request at least 45 calendar days before 
commencing manufacture or import.
    (c) Contents of the Tier II exemption request. Each person who 
submits a request under this subpart must provide the information 
described in Sec. Sec. 725.428 and 725.455, as well as information 
sufficient to enable EPA to evaluate the effects of all activities 
described in the request.
    (d) Recordkeeping. Each person who submits a request under this 
subpart must comply with the recordkeeping requirements of Sec. 725.65. 
In addition, the submitter should maintain records which contain 
information that verifies compliance with the following:
    (1) The certifications made in the request.
    (2) All the eligibility criteria for the Tier II exemption request 
including the criteria for the recipient microorganism, the introduced 
genetic material, the physical containment and control technologies.


Sec. 725.455   Information to be included in the Tier II exemption 
request.

    The applicant must indicate clearly that the submission is an Tier 
II exemption request for a microorganism instead of the MCAN under 
subpart D of this part and must submit the following information:
    (a) Submitter identification. (1) The name and headquarters address 
of the submitter.
    (2) The name, address, and office telephone number (including area 
code) of the principal technical contact representing the submitter.
    (b) Microorganism identity information. (1) Identification (genus, 
species, and strain) of the recipient microorganism. Genus, species 
designation should be substantiated by a letter from a culture 
collection or a brief summary of the results of tests conducted for 
taxonomic identification.
    (2) Type of genetic modification and the function of the introduced 
genetic material.
    (3) Site of insertion.
    (4) Certification of compliance with the introduced genetic 
material criteria described in Sec. 725.421.
    (c) Production volume. Production volume, including total liters 
per year, and the maximum cell concentration achieved during the 
production process.
    (d) Process and containment information. (1) A description of the 
process including the following:
    (i) Identity and location of the manufacturing site(s).
    (ii) Process flow diagram illustrating the production process, 
including downstream separations, and indicating the containment 
envelope around the appropriate equipment.
    (iii) Identities and quantities of feedstocks.
    (iv) Sources and quantities of potential releases to both the 
workplace and environment, and a description of engineering controls, 
inactivation procedures, and other measures which will reduce worker 
exposure and environmental releases.
    (v) A description of procedures which will be undertaken to prevent 
fugitive emissions, i.e. leak detection and repair program.
    (vi) A description of procedures/safeguards to prevent and mitigate 
accidental releases to the workplace and the environment.
    (2) Certification of those elements of the containment criteria 
described in Sec. 725.422 with which the manufacturer is in compliance, 
including stating by number the elements with which the manufacturer is 
in full compliance.


Sec. 725.470   EPA review of the Tier II exemption request.

    General procedures for review of all submissions under this part 
are contained in Sec. Sec. 725.28 through 725.60. In addition, the 
following procedures apply to EPA review of requests submitted under 
this subpart:
    (a) Length of the review period. The review period for the request 
will be 45 days from the date the Document Control Officer for the 
Office of Pollution Prevention and Toxics receives a complete request, 
or the date EPA determines the request is complete under Sec. 725.33, 
unless the Agency extends the review period for good cause under 
Sec. 725.56.
    (b) Criteria for review. EPA will review the request to determine 
that the new microorganism complies with Sec. 725.428 and that its use 
as described in the request will not present an unreasonable risk of 
injury to health or the environment.
    (c) EPA decision regarding the Tier II exemption request. A 
decision concerning a request under this subpart will be made by the 
Administrator, or a designee.
    (d) Determination that the microorganism is ineligible for a Tier 
II review. (1) EPA may determine that the manufacturer or importer is 
not eligible for Tier II review, because the microorganism does not 
meet the criteria under Sec. 725.428 or the Administrator, or a 
designee, decides that there is insufficient information to determine 
that the conditions of use of the microorganism as described in the 
request will not present an unreasonable risk to health or the 
environment.
    (2) If the Agency makes this determination, the Administrator, or a 
designee will notify the manufacturer by telephone, followed by a 
letter, that the request has been denied. The letter will explain 
reasons for the denial.
    (3) If the request is denied, the manufacturer may submit the 
information necessary to constitute a MCAN under subpart D of this 
part.
    (e) Approval or denial of the Tier II exemption request. (1) No 
later than 45 days after EPA receives a request, the Agency will either 
approve or deny the request.
    (2) In approving a request, EPA may impose any restrictions 
necessary to ensure that the microorganism will not present an 
unreasonable risk of injury to health and the environment as a result 
of general commercial use.
    (f) EPA may seek to enjoin the manufacture or import of a 
microorganism in violation of this subpart, or act to seize any 
microorganism manufactured or imported in violation of this section or 
take other actions under the authority of sections 7 or 17 of the Act.
Subparts H-K--[Reserved]
Subpart L--Additional Procedures for Reporting on Significant New Uses 
of Microorganisms


Sec. 725.900   Scope and purpose.

    (a) This subpart describes additional provisions governing 
submission of MCANs for microorganisms subject to significant new use 
rules identified in subpart M of this part.
    (b) Manufacturers, importers, and processors described in 
Sec. 725.105(c) must submit a MCAN under subpart D of this part for 
significant new uses of microorganisms described in subpart M of this 
part, unless they are excluded under Sec. Sec. 725.910 and 725.912.
    (c) Section 725.920 discusses exports and imports.
    (d) Additional recordkeeping requirements specific to significant 
new uses of microorganisms are described in Sec. 725.950.
    (e) Section 725.975 describes how EPA will approve alternative 
means of complying with significant new use requirements designated in 
subpart M of this part.
    (f) Expedited procedures for promulgating significant new use 
requirements under subpart M of this part for microorganisms subject to 
section 5(e) orders are discussed in Sec. Sec. 725.980 and 725.984.


Sec. 725.910   Persons excluded from reporting on significant new uses.

    (a) A person who intends to manufacture, import, or process a 
microorganism identified in subpart M of this part and who intends to 
distribute it in commerce is not required to submit a MCAN under 
subpart D of this part, if that person can document one or more of the 
following as to each recipient of the microorganism from that person:
    (1) That the person has notified the recipient, in writing, of the 
specific section in subpart M of this part which identifies the 
microorganism and its designated significant new uses.
    (2) That the recipient has knowledge of the specific section in 
subpart M of this part which identifies the microorganism and its 
designated significant new uses.
    (3) That the recipient cannot undertake any significant new use 
described in the specific section in subpart M of this part.
    (b) The manufacturer, importer, or processor described in paragraph 
(a) of this section must submit a MCAN under subpart D of this part, if 
such person has knowledge at the time of commercial distribution of the 
microorganism identified in the specific section in subpart M of this 
part that a recipient intends to engage in a designated significant new 
use of that microorganism without submitting a MCAN under this part.
    (c) A person who processes a microorganism identified in a specific 
section in subpart M of this part for a significant new use of that 
microorganism is not required to submit a MCAN if that person can 
document each of the following:
    (1) That the person does not know the specific microorganism 
identity of the microorganism being processed.
    (2) That the person is processing the microorganism without 
knowledge that the microorganism is identified in subpart M of this 
part.
    (d)(1) If at any time after commencing distribution in commerce of 
a microorganism identified in a specific section in subpart M of this 
part, a person who intends to manufacture, import, or process a 
microorganism described in subpart M of this part and intends to 
distribute it in commerce has knowledge that a recipient of the 
microorganism is engaging in a significant new use of that 
microorganism designated in that section without submitting a MCAN 
under this part, the person is required to cease supplying the 
microorganism to that recipient and to submit a MCAN for that 
microorganism and significant new use, unless the person is able to 
document each of the following:
    (i) That the person has notified the recipient and EPA enforcement 
authorities (at the address in paragraph (d)(1)(iii) of this section), 
in writing within 15 working days of the time the person develops 
knowledge that the recipient is engaging in a significant new use, that 
the recipient is engaging in a significant new use without submitting a 
MCAN.
    (ii) That, within 15 working days of notifying the recipient as 
described in paragraph (d)(1)(i) of this section, the person received 
from the recipient, in writing, a statement of assurance that the 
recipient is aware of the terms of the applicable section in subpart M 
of this part and will not engage in the significant new use.
    (iii) That the person has promptly provided EPA enforcement 
authorities with a copy of the recipient's statement of assurance 
described in paragraph (d)(1)(ii) of this section. The copy must be 
sent to the Director, Office of Compliance Monitoring (EN-342), 
Environmental Protection Agency, 401 M St., SW., Washington, DC 20460.
    (2) If EPA notifies the manufacturer, importer, or processor that 
the recipient is engaging in a significant new use after providing the 
statement of assurance described in paragraph (d)(1)(ii) of this 
section and without submitting a MCAN under this part, the 
manufacturer, importer, or processor shall immediately cease 
distribution to that recipient until the manufacturer, importer, or 
processor or the recipient has submitted a MCAN under this part and the 
MCAN review period has ended.
    (3) If, after receiving a statement of assurance from a recipient 
under paragraph (d)(1)(ii) of this section, a manufacturer, importer, 
or processor has knowledge that the recipient is engaging in a 
significant new use without submitting a MCAN under this part, the 
manufacturer, importer, or processor must immediately cease 
distributing the microorganism to that recipient and notify EPA 
enforcement authorities at the address identified in paragraph 
(c)(1)(iii) of this section. The manufacturer, importer, or processor 
may not resume distribution to that recipient until any one of the 
following has occurred:
    (i) The manufacturer, importer, or processor has submitted a MCAN 
under this part and the MCAN review period has ended.
    (ii) The recipient has submitted a MCAN under this part and the 
MCAN review period has ended.
    (iii) The manufacturer, importer, or processor has received notice 
from EPA enforcement authorities that it may resume distribution to 
that recipient.


Sec. 725.912   Exemptions.

    Persons identified in Sec. Sec. 725.100(c) and 725.910 are not 
required to submit a MCAN under subpart D of this part for a 
microorganism identified in subpart M of this part, unless otherwise 
specified in a specific section in subpart M, if:
    (a) The person submits a MCAN for the microorganism prior to the 
promulgation date of the section in subpart M of this part which 
identifies the microorganism, and the person receives written 
notification of compliance from EPA prior to the effective date of such 
section. The MCAN submitter must comply with any applicable requirement 
of section 5(b) of the Act. The MCAN must include the information and 
test data specified in section 5(d)(1) of the Act. For purposes of this 
exemption, the specific section in subpart M of this part which 
identifies the microorganism and Sec. Sec. 725.3, 725.15, 725.65, 
725.70, 725.75, 725.100, and 725.900 apply; after the effective date of 
the section in subpart M of this part which identifies the 
microorganism, Sec. Sec. 725.105 and 725.910 apply and Sec. 725.920 
continues to apply. EPA will provide the MCAN submitter with written 
notification of compliance only if one of the following occurs:
    (1) EPA is unable to make the finding that the activities described 
in the MCAN will or may present an unreasonable risk of injury to 
health or the environment under reasonably foreseeable circumstances.
    (2) EPA and the person negotiate a consent order under section 5(e) 
of the Act, such order to take effect on the effective date of the 
section in subpart M of this part which identifies the microorganism.
    (b) The person is operating under the terms of a consent order 
issued under section 5(e) of the Act applicable to that person. If a 
provision of such section 5(e) order is inconsistent with a specific 
significant new use identified in subpart M of this part, abiding by 
the provision of the section 5(e) order exempts the person from 
submitting a MCAN for that specific significant new use.


Sec. 725.920   Exports and imports.

    (a) Exports. Persons who intend to export a microorganism 
identified in subpart M of this part, or in any proposed rule which 
would amend subpart M of this part, are subject to the export 
notification provisions of section 12(b) of the Act. The regulations 
that interpret section 12(b) appear at 40 CFR part 707.
    (b) Imports. Persons who import a substance identified in a 
specific section in subpart M of this part are subject to the import 
certification requirements under section 13 of the Act, which are 
codified at 19 CFR Sec. Sec. 12.118 through 12.127 and 12.28. The EPA 
policy in support of the import certification requirements appears at 
40 CFR part 707.


Sec. 725.950   Additional recordkeeping requirements for reporting of 
significant new uses.

    Persons submitting a MCAN for a significant new use of a 
microorganism must comply with the recordkeeping requirements of 
Sec. 725.65. In addition, the following requirements apply:
    (a) At the time EPA adds a microorganism to subpart M of this part, 
the Agency may specify appropriate recordkeeping requirements. Each 
manufacturer, importer, and processor of the microorganism shall 
maintain the records for 3 years from the date of their creation.
    (b) The records required to be maintained under this section may 
include the following:
    (1) Records documenting the information contained in the MCAN 
submitted to the Agency.
    (2) Records documenting the manufacture and importation volume of 
the microorganism and the corresponding dates of manufacture and 
import.
    (3) Records documenting volumes of the microorganism purchased 
domestically by processors of the microorganism, names and addresses of 
suppliers and corresponding dates of purchase.
    (4) Records documenting the names and addresses (including shipment 
destination address, if different) of all persons outside the site of 
manufacture or import to whom the manufacturer, importer, or processor 
directly sells or transfers the microorganism, the date of each sale or 
transfer, and the quantity of the microorganism sold or transferred on 
such date.


Sec. 725.975   EPA approval of alternative control measures.

    (a) In certain sections of subpart M of this part, significant new 
uses for the identified microorganisms are described as the failure to 
establish and implement programs providing for the use of either: 
specific measures to control worker exposure to or release of 
microorganisms which are identified in such sections, or alternative 
measures to control worker exposure or environmental release which EPA 
has determined provide substantially the same degree of protection as 
the specified control measures. Persons who manufacture, import, or 
process a microorganism identified in such sections and who intend to 
employ alternative measures to control worker exposure or environmental 
release must submit a request to EPA for a determination of equivalency 
before commencing manufacture, import, or processing involving the 
alternative control measures.
    (b) A request for a determination of equivalency must be submitted 
in writing to the Office of Pollution Prevention and Toxics, Document 
Control Officer, 7407, 401 M St., SW., Washington, DC 20460: ATTN: SNUR 
Equivalency Determination, and must contain:
    (1) The name of the submitter.
    (2) The specific identity of the microorganism.
    (3) The citation for the specific section in subpart M of this part 
which pertains to the microorganism for which the request is being 
submitted.
    (4) A detailed description of the activities involved.
    (5) The specifications of the alternative worker exposure control 
measures or environmental release control measures.
    (6) An analysis justifying why such alternative control measures 
provide substantially the same degree of protection as the specific 
control measures identified in the specific section in subpart M of 
this part which pertains to the microorganism for which the request is 
being submitted.
    (7) The data and information described in Sec. Sec. 725.155 and 
725.160 of this part unless such data and information have already been 
submitted to EPA's Office of Pollution Prevention and Toxics.
    (c) Requests for determinations of equivalency will be reviewed by 
EPA within 45 days. Determinations under this paragraph will be made by 
the Director, or a designee. Notice of the results of such 
determinations will be mailed to the submitter.
    (d) If EPA notifies the submitter under paragraph (c) of this 
section that EPA has determined that the alternative control measures 
provide substantially the same degree of protection as the specified 
control measures identified in the specific section of subpart M of 
this part which pertains to the microorganism for which the request is 
being submitted, the submitter may commence manufacture, import, or 
processing in accordance with the specifications for alternative worker 
exposure control measures or environmental release control measures 
identified in the submitter's request, and may alter any corresponding 
notification to workers to reflect such alternative controls. 
Deviations from the activities described in the EPA notification 
constitute a significant new use and are subject to the requirements of 
this part.


Sec. 725.980   Expedited procedures for issuing significant new use 
rules for microorganisms subject to section 5(e) orders.

    (a) Selection of microorganisms. (1) In accordance with the 
expedited process specified in this section, EPA will issue significant 
new use notification requirements for each new microorganism that, 
after MCAN review under subpart D of this part, becomes subject to a 
final order issued under section 5(e) of the Act, except for an order 
that prohibits manufacture and import of the microorganism, unless EPA 
determines that significant new use notification requirements are not 
needed for the microorganism.
    (2) If EPA determines that significant new use notifications 
requirements are not needed for a microorganism that is subject to a 
final order issued under section 5(e) of the Act, EPA will issue a 
notice in the Federal Register explaining why the significant new use 
requirements are not needed.
    (b) Designation of requirements. (1) The significant new use 
notification and other specific requirements will be based on and be 
consistent with the provisions included in the final order issued for 
the microorganism under section 5(e) of the Act. EPA may also designate 
additional activities as significant new uses which will be subject to 
notification.
    (2) Significant new use requirements and other specific 
requirements designated under this section will be listed in subpart M 
of this part. For each microorganism, subpart M of this part will 
identify:
    (i) The microorganism name.
    (ii) The activities designated as significant new uses.
    (iii) Other specific requirements applicable to the microorganism, 
including recordkeeping requirements or any other requirements included 
in the final section 5(e) order.
    (c) Procedures for issuing significant new use rules. (1) Possible 
processes. EPA will issue significant new use rules under this section 
by one of the following three processes: direct final rulemaking, 
interim final rulemaking, or notice and comment rulemaking. EPA will 
use the direct final rulemaking process to issue significant new use 
rules unless it determines that, in a particular case, one of the other 
processes is more appropriate.
    (2) Notice in the Federal Register. Federal Register documents 
issued to propose or establish significant new uses under this section 
will contain the following:
    (i) The microorganism identity or, if its specific identity is 
claimed confidential, an appropriate generic microorganism name and an 
accession number assigned by EPA.
    (ii) The MCAN number.
    (iii) A summary of EPA's findings under section 5(e)(1)(A) of the 
Act for the final order issued under section 5(e).
    (iv) Designation of the significant new uses subject to, or 
proposed to be subject to, notification and any other applicable 
requirements.
    (v) Any modification of subpart M of this part applicable to the 
specific microorganism and significant new uses.
    (vi) If the Federal Register document establishes a final rule, or 
notifies the public that a final rule will not be issued after public 
comment has been received, the document will describe comments received 
and EPA's response.
    (3) Direct final rulemaking. (i) EPA will use the direct final 
rulemaking procedure to issue a significant new use rule, when specific 
requirements will be based on and be consistent with the provisions 
included in the final order issued for the microorganism under section 
5(e) of the Act. The Agency will issue a final rule in the Federal 
Register following its decision to develop a significant new use rule 
under this section for a specific new microorganism.
    (ii) The Federal Register document will state that, unless written 
notice is received by EPA within 30 days of publication that someone 
wishes to submit adverse or critical comments, the rule will be 
effective 60 days from the date of publication. The written notice of 
intent to submit adverse or critical comments should state which 
SNUR(s) will be the subject of the adverse or critical comments, if 
several SNURs are established through the direct final rule. If notice 
is received within 30 days that someone wishes to submit adverse or 
critical comments, the section(s) of the direct final rule containing 
the SNUR(s) for which a notice of intent to comment was received will 
be withdrawn by EPA issuing a document in the final rule section of the 
Federal Register, and a proposal will be published in the proposed rule 
section of the Federal Register. The proposal will establish a 30-day 
comment period.
    (iii) If EPA, having considered any timely comments submitted in 
response to the proposal, decides to establish notification 
requirements under this section, EPA will issue a final rule adding the 
microorganism to subpart M of this part and designating the significant 
new uses subject to notification.
    (4) Interim final rulemaking. (i) EPA will use the interim final 
rulemaking procedure to issue a significant new use rule, when specific 
requirements will be based on and be consistent with the provisions 
included in the final order issued for the microorganism under section 
5(e) of the Act. The Agency will issue an interim final rule in the 
Federal Register following its decision to develop a significant new 
use rule for a specific new microorganism. The document will state 
EPA's reasons for using the interim final rulemaking procedure.
    (A) The significant new use rule will take effect on the date of 
publication.
    (B) Persons will be given 30 days from the date of publication to 
submit comments.
    (ii) Interim final rules issued under this section shall cease to 
be in effect 180 days after publication unless, within the 180-day 
period, EPA issues a final rule in the Federal Register responding to 
any written comments received during the 30-day comment period 
specified in paragraph (c)(5)(i)(B) of this section and promulgating 
final significant new use notification requirements and other 
requirements for the microorganism.
    (5) Notice and comment rulemaking. (i) EPA will use a notice and 
comment procedure to issue a significant new use rule, when EPA is 
designating additional activities which are not provisions included in 
the final order issued for the microorganism under section 5(e) of the 
Act as significant new uses which will be subject to notification. EPA 
will issue a proposal in the Federal Register following its decision to 
develop a significant new use rule under this section for a specific 
new microorganism. Persons will be given 30 days to comment on whether 
EPA should establish notification requirements for the microorganism 
under this part.
    (ii) If EPA, having considered any timely comments, decides to 
establish notification requirements under this section, EPA will issue 
a final rule adding the microorganism to subpart M of this part and 
designating the significant new uses subject to notification.
    (d) Schedule for issuing significant new use rules. (1) Unless EPA 
determines that a significant new use rule should not be issued under 
this section, EPA will issue a proposed rule, a direct final rule, or 
an interim final rule within 180 days of receipt of a valid notice of 
commencement under Sec. 725.190 of this part.
    (2) If EPA receives adverse or critical significant comments 
following publication of a proposed or interim final rule, EPA will 
either withdraw the rule or issue a final rule addressing the comments 
received.


Sec. 725.984   Modification or revocation of certain notification 
requirements.

    (a) Criteria for modification or revocation. EPA may at any time 
modify or revoke significant new use notification requirements for a 
microorganism which has been added to subpart M of this part using the 
procedures of Sec. 725.980. Such action may be taken under this section 
if EPA makes one of the following determinations, unless other 
information shows that the requirements should be retained:
    (1) Test data or other information obtained by EPA provide a 
reasonable basis for concluding that activities designated as 
significant new uses of the microorganism will not present an 
unreasonable risk of injury to health or the environment.
    (2) EPA has promulgated a rule under section 4 or 6 of the Act, or 
EPA or another agency has taken action under another law, for the 
microorganism that eliminates the need for significant new use 
notification under section 5(a)(2) of the Act.
    (3) EPA has received MCANs for some or all of the activities 
designated as significant new uses of the microorganism and, after 
reviewing such MCANs, concluded that there is no need to require 
additional notice from persons who propose to engage in identical or 
similar activities.
    (4) For a microorganism added to subpart M of this part under 
Sec. 725.980, EPA has examined new information, or has reexamined the 
test data or other information supporting its finding under section 
5(e)(1)(A)(ii)(I) of the Act and has concluded that a rational basis no 
longer exists for the findings that activities involving the 
microorganism may present an unreasonable risk of injury to human 
health or the environment required under section 5(e)(1)(A) of the Act.
    (5) For a microorganism added to subpart M of this part under 
Sec. 725.980, certain activities involving the microorganism have been 
designated as significant new uses pending the completion of testing, 
and adequate test data developed in accordance with applicable 
procedures and criteria have been submitted to EPA.
    (b) Procedures for limitation or revocation. Modification or 
revocation of significant new use notification requirements for a 
microorganism that has been added to subpart M of this part using the 
procedures described in Sec. 725.980 may occur either at EPA's 
initiative or in response to a written request.
    (1) Any affected person may request modification or revocation of 
significant new use notification requirements for a microorganism that 
has been added to subpart M of this part using the procedures described 
in Sec. 725.980 by writing to the Director, or a designee, and stating 
the basis for such request. The request must be accompanied by 
information sufficient to support the request. All requests should be 
sent to the TSCA Document Processing Center (7407), Room L-100, U.S. 
Environmental Protection Agency, 401 M St., SW., Washington, DC 20460, 
ATTN: Request to amend SNUR.
    (2) The Director, or a designee, will consider the request, make a 
determination whether to initiate rulemaking to modify the 
requirements, and notify the requester of that determination by 
certified letter. If the request is denied, the letter will explain why 
EPA has concluded that the significant new use notification 
requirements for that microorganism should remain in effect.
    (3) If EPA concludes that significant new use notification 
requirements for a microorganism should be limited or revoked, EPA will 
propose the changes in a notice in the Federal Register, briefly 
describe the grounds for the action, and provide interested parties an 
opportunity to comment.
Subpart M--Significant New Uses for Specific Microorganisms--[Reserved]

[FR Doc. 94-21359 Filed 8-31-94; 8:45 am]
BILLING CODE 6560-50-F