[Federal Register Volume 64, Number 130 (Thursday, July 8, 1999)]
[Notices]
[Pages 37002-37009]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-17315]



[[Page 37001]]

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Part III





Environmental Protection Agency





_______________________________________________________________________



Pesticides; Policy Issues Related to the Food Quality Protection Act; 
Notice

  Federal Register / Vol. 64, No. 130 / Thursday, July 8, 1999 / 
Notices  

[[Page 37002]]


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ENVIRONMENTAL PROTECTION AGENCY

[OPP-00610; FRL-6088-7]


Pesticides; Policy Issues Related to the Food Quality Protection 
Act

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice of availability.

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SUMMARY: To assure that EPA's policies related to implementing the Food 
Quality Protection Act (FQPA) are transparent and open to public 
participation, EPA is soliciting comments on four policy papers 
entitled ``Toxicology Data Requirements for Assessing Risks of 
Pesticide Exposure to Children's Health,'' ``Exposure Data Requirement 
for Assessing Risks of Pesticide Exposure to Children,'' ``The Office 
of Pesticide Programs' Policy on Determination of the Appropriate FQPA 
Safety Factor(s) for Use in the Tolerance-Setting Process,'' and 
``Standard Operating Procedures (SOP) for Determining the Appropriate 
FQPA Safety Factor(s) for Use in Tolerance Assessment.'' This notice is 
the ninth in a series concerning science policy documents related to 
FQPA and developed through the Tolerance Reassessment Advisory 
Committee (TRAC).

DATES: Written comments for these policy papers, identified under one 
docket control number provided in Unit I. of this document, should be 
submitted by September 7, 1999.

ADDRESSES: Comments may be submitted by mail, electronically, or in 
person. Please follow the detailed instructions for each method as 
provided in Unit I.C. of this document. To ensure proper receipt by 
EPA, it is imperative that you identify docket control number OPP-00610 
in the subject line on the first page of your response.

FOR FURTHER INFORMATION CONTACT: Penelope A. Fenner-Crisp, 
Environmental Protection Agency (7501C), 401 M St., SW., Washington, DC 
20460; telephone number: (703) 605-0654; fax: 703-305-4776; e-mail: 
[email protected].

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Notice Apply to Me?

    You may be potentially affected by this notice if you manufacture 
or formulate pesticides. Potentially affected categories and entities 
may include, but are not limited to:

 
------------------------------------------------------------------------
                                                          Examples of
           Categories                    NAICS            Potentially
                                                       Affected Entities
------------------------------------------------------------------------
Pesticide Producers               32532               Pesticide
                                                       manufacturers
                                                      Pesticide
                                                       formulators
------------------------------------------------------------------------

    This listing is not intended to be exhaustive, but rather provides 
a guide for readers regarding entities likely to be affected by this 
action. Other types of entities not listed could also be affected. If 
available, the North American Industrial Classification System (NAICS) 
codes have been provided to assist you and others in determining 
whether or not this notice affects certain entities. If you have any 
questions regarding the applicability of this announcement to you, 
consult the person listed in the ``FOR FURTHER INFORMATION CONTACT'' 
section.

B. How Can I Get Additional Information or Copies of This Document or 
Other Documents?

    1. Electronically. You may obtain electronic copies of this 
document and the four science policy papers from the EPA Home Page 
under the Office of Pesticide Programs (OPP) at http://www.epa.gov/
pesticides/. On the Office of Pesticide Program Home Page select 
``TRAC'' and then look up the entry for this document. You can also go 
directly to the listings at the EPA Home Page at the Federal Register--
Environmental Documents entry for this document under ``Laws and 
Regulations'' (http://www.epa.gov/fedrgstr/) to obtain this notice and 
the four science policy papers.
    2. In person or by phone. If you have any questions or need 
additional information about this action, you may contact the person 
identified in the ``FOR FURTHER INFORMATION CONTACT'' section of this 
document. In addition, the official records for the science policy 
papers listed in the SUMMARY section of this document, including the 
public version, have been established under the docket control number 
OPP-00610 (including comments and data submitted electronically as 
described below). This record not only includes the documents that are 
physically located in the docket, but also includes all the documents 
that are referenced in those documents. Public versions of these 
records, including printed, paper versions of any electronic comments, 
which do not include any information claimed as Confidential Business 
Information (CBI), are available for inspection in Rm. 119, Crystal 
Mall #2, 1921 Jefferson Davis Highway, Arlington, VA, from 8:30 a.m. to 
4 p.m., Monday through Friday, excluding legal holidays. The Public 
Information and Records Integrity Branch telephone number is 703-305-
5805.

C. How and to Whom Do I Submit Comments?

    You may submit comments through the mail, in person, or 
electronically. To ensure proper receipt by EPA, it is imperative that 
you identify docket control number OPP-00610 in the subject line on the 
first page of your response.
    1. By mail. Submit written comments to: Public Information and 
Records Integrity Branch, Information Resources and Services Division 
(7502C), Office of Pesticide Programs, Environmental Protection Agency, 
401 M St., SW., Washington, DC 20460.
    2. In person or by courier. Deliver written comments to: Public 
Information and Records Integrity Branch, Information Resources and 
Services Division (7502C), Office of Pesticide Programs, Environmental 
Protection Agency, Rm. 119, Crystal Mall #2, 1921 Jefferson Davis 
Highway, Arlington, VA.
    3. Electronically. Submit your comments and/or data electronically 
by e-mail to: [email protected]. Do not submit any information 
electronically that you consider to be CBI. Submit electronic comments 
as an ASCII file, avoiding the use of special characters and any form 
of encryption. Comments and data will also be accepted on standard 
computer disks in WordPerfect 5.1/6.1 or ASCII file format. All 
comments and data in electronic form must be identified by the docket 
control number. Electronic comments on this notice may also be filed 
online at many Federal Depository Libraries.

D. How Should I Handle CBI Information That I Want to Submit to the 
Agency?

    You may claim information that you submit in response to this 
document as CBI by marking any part or all of that information as CBI. 
Information so marked will not be disclosed except in accordance with 
procedures set forth in 40 CFR part 2. In addition to one complete 
version of the comment that includes any information claimed as CBI, a 
copy of the comment that does not contain CBI must be submitted for 
inclusion in the public record. Information not marked confidential

[[Page 37003]]

will be included in the public docket by EPA without prior notice. If 
you have any questions about CBI or the procedures for claiming CBI, 
please call the Public Information and Records Integrity Branch; the 
telephone number is (703) 305-5805.

E. What Should I Consider As I Prepare My Comments for EPA?

    EPA invites you to provide your views on the draft science policy 
papers, new approaches the Agency has not considered, the potential 
impacts of the various options (including possible unintended 
consequences), and any data or information that you would like the 
Agency to consider. You may find the following suggestions helpful for 
preparing your comments:
    1. Explain your views as clearly as possible.
    2. Describe any assumptions that you used.
    3. Provide solid technical information and/or data to support your 
views.
    4. If you estimate potential burden or costs, explain how you 
arrived at the estimate.
    5. Indicate what you support, as well as what you disagree with.
    6. Provide specific examples to illustrate your concerns.
    7. Make sure to submit your comments by the deadline in this 
notice.
    8. At the beginning of your comments (e.g., as part of the 
``subject'' heading), be sure to properly identify the document you are 
commenting on. To ensure proper receipt by EPA, it is imperative that 
you identify docket control number OPP-00610 in the subject line on the 
first page of your response. You may also provide the name, date, and 
Federal Register citation.

II. Background for the Tolerance Reassessment Advisory Committee 
(TRAC)

    On August 3, 1996, the Food Quality Protection Act of 1996 (FQPA) 
was signed into law. Effective upon signature, the FQPA significantly 
amended the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) 
and the Federal Food, Drug, and Cosmetic Act (FFDCA). Among other 
changes, FQPA established a stringent health-based standard (``a 
reasonable certainty of no harm'') for pesticide residues in foods to 
assure protection from unacceptable pesticide exposure; provided 
heightened health protections for infants and children from pesticide 
risks; required expedited review of new, safer pesticides; created 
incentives for the development and maintenance of effective crop 
protection tools for farmers; required reassessment of existing 
tolerances over a 10-year period; and required periodic re-evaluation 
of pesticide registrations and tolerances to ensure that scientific 
data supporting pesticide registrations will remain up-to-date in the 
future.
    Subsequently, the Agency established the Food Safety Advisory 
Committee (FSAC) as a subcommittee of the National Advisory Council for 
Environmental Policy and Technology (NACEPT) to assist in soliciting 
input from stakeholders and to provide input to EPA on some of the 
broad policy choices facing the Agency and on strategic direction for 
the Office of Pesticide Programs. The Agency has used the interim 
approaches developed through discussions with the FSAC to make 
regulatory decisions that met FQPA's standard, but that could be 
revisited if additional information became available or as the science 
evolved. As EPA's approach to implementing the scientific provisions of 
FQPA has evolved, the Agency has sought independent review and public 
participation, often through presentation of many of the science policy 
issues to the FIFRA Scientific Advisory Panel (SAP), a group of 
independent, outside experts who provide peer review and scientific 
advice to OPP.
    In addition, as directed by Vice President Albert Gore, EPA has 
been working with the U.S. Department of Agriculture (USDA) and another 
subcommittee of NACEPT, the Tolerance Reassessment Advisory Committee 
(TRAC), chaired by the EPA Deputy Administrator and the USDA Deputy 
Secretary, to address FQPA issues and implementation. TRAC comprises 
more than 50 representatives of affected user, producer, consumer, 
public health, environmental, states and other interested groups. The 
TRAC has met six times as a full committee from May 27, 1998 through 
April 29, 1999.
    The Agency has been working with TRAC to ensure that its science 
policies, risk assessments of individual pesticides, and process for 
decision-making are transparent and open to public participation. An 
important product of these consultations with TRAC is the development 
of a framework for addressing key science policy issues.
    The Agency decided that the FQPA implementation process and related 
policies would benefit from initiating notice and comment on the major 
science policy issues. TRAC identified nine science policy issue areas 
they believe were key to implementation of FQPA and tolerance 
reassessment. The framework calls for EPA to provide one or more 
documents for comment on each of the nine issues by announcing their 
availability in the Federal Register. In accordance with the framework 
described in a separate notice published in the Federal Register of 
October 29, 1998 (63 FR 58038) (FRL-6041-5), EPA has been issuing a 
series of draft documents concerning the nine science policy issues 
identified by the TRAC related to the implementation of FQPA. This 
notice announces the availability of the four documents identified in 
the SUMMARY section of this document.

III. Background on FQPA Safety Factor Papers

A. 1993 National Research Council (NRC) Study

    In response to a request from the U.S. Congress, the National 
Research Council (NRC) conducted a study on the scientific and policy 
issues concerning pesticides in the diets of infants and children. In 
its 1993 report, ``Pesticides in the Diets of Infants and Children,'' 
the NRC concluded that although the uncertainty factors that are widely 
used to establish guidelines for human exposure on the basis of animal 
testing results generally provide adequate protection for infants and 
children, children may be uniquely susceptible to chemical exposures at 
particularly sensitive stages of development. The NRC further 
concluded, ``in the absence of data to the contrary, there should be a 
presumption of greater toxicity to infants and children.''

B. Applicable FQPA Requirements

    The Food Quality Protection Act (FQPA) of 1996 (Public Law 104-170) 
was signed into law on August 3, 1996. FQPA establishes a new safety 
standard and new procedures for EPA's pesticide tolerance-setting 
activities. Under new section 408(b)(2)(A)(i) of FFDCA, EPA can 
establish, revise or leave in effect a tolerance (the legal limit for a 
pesticide chemical residue in or on a food) only if it is determined to 
be ``safe.'' Section 408(b)(2)(A)(ii) defines ``safe'' to mean that 
``there is a reasonable certainty that no harm will result from 
aggregate exposure to the pesticide chemical residue, including all 
anticipated dietary exposures and all other exposures for which there 
is reliable information.'' Section 408(b)(2)(C) requires EPA to give 
special consideration to infants and children by ensuring ``that there 
is a reasonable certainty that no harm will result to infants and 
children from aggregate

[[Page 37004]]

exposure to the pesticide chemical residue.''
    FQPA instructs EPA, in making its ``reasonable certainty of no 
harm'' finding, that in ``the case of threshold effects, . . . an 
additional tenfold margin of safety for the pesticide chemical residue 
and other sources of exposure shall be applied for infants and children 
to take into account potential pre- and post-natal toxicity and 
completeness of data with respect to exposure and toxicity to infants 
and children.'' Section 408(b)(2)(c) further states that ``the 
Administrator may use a different margin of safety for the pesticide 
chemical residue only if, on the basis of reliable data, such margin 
will be safe for infants and children.''

C. EPA 10X Task Force

    In March 1998, the U.S. Environmental Protection Agency (EPA) 
established an agency-wide ``10X Task Force'' to address the use of the 
ten-fold (10X) margin of safety for infants and children (otherwise 
known as the ``FQPA Safety Factor'') provided for in the Food Quality 
Protection Act (FQPA) of 1996. Task Force members included high-level 
scientists primarily from the Office of Children's Health Protection, 
the Office of Prevention, Pesticides and Toxic Substances, and the 
Office of Research and Development. This group was charged with 
developing recommendations regarding the implementation of the FQPA 
Safety Factor.
    In response to this charge, the 10X Task Force formed two working 
groups--the Toxicology Working Group and the Exposure Working Group. 
These groups have each drafted a report ``Toxicology Data Requirements 
for Assessing Risks of Pesticide Exposure to Children's Health'' and 
``Exposure Data Requirements for Assessing Risks of Pesticide Exposure 
to Children,'' respectively, which are summarized in Units IV.A. and 
IV.B. of this document. These reports contain recommendations 
concerning the implementation of the FQPA Safety Factor.

D. Pesticide Program Guidance

    The Office of Pesticide Programs (OPP) is responsible for 
implementing the requirements of FQPA in making its pesticide 
regulatory decisions daily. Accordingly, OPP has developed updated, 
interim guidance as to how it will comply with FQPA concerning the FQPA 
Safety Factor for protecting infants and children. In drafting this 
guidance, OPP has taken into account the recommendations of the 10X 
Task Force as embodied in the above-mentioned documents. OPP's guidance 
consists of two documents: ``The Office of Pesticide Programs' Guidance 
Document on the Determination of the Appropriate FQPA Safety Factor(s) 
for Use in the Setting of Tolerances'' and ``Standard Operating 
Procedures (SOP) for Determining the Appropriate FQPA Safety Factor(s) 
for Use in Tolerance Reassessment'' which are summarized in Units IV.C. 
and IV.D. of this document. The former paper explains the general 
policies that OPP proposes to follow in making determinations 
concerning the use of the FQPA Safety Factor, while the latter paper 
specifies the detailed procedures that OPP will use in following these 
policies.

E. Scientific Peer Review

    Since the FQPA was promulgated, OPP has submitted all interim 
policy and guidance documents on the FQPA safety factor for independent 
scientific peer review, with concurrent requests for public comment. 
Responses and comments received from the independent scientific panels, 
other offices within the Agency, government agencies, and from the 
public sector, in response to each of these document releases and/or 
presentations, have been carefully considered throughout the process of 
developing interim policy. The first interim policy paper explaining 
the OPP position on the use of the ten-fold margin of safety, was 
presented to the FIFRA Scientific Advisory Panel (SAP) in October 1996. 
In March 1998, a second OPP interim policy paper on the application of 
the ten-fold safety factor to risk assessments entitled ``Presentation 
for FIFRA Scientific Advisory Panel by Office of Pesticide Programs 
Health Effects Division on FQPA Safety Factor for Infants and 
Children,'' was presented to the SAP. An update on the Agency's 
progress in addressing issues raised by the SAP was brought before a 
subsequent Panel in July 1998; however, the primary positions described 
in the March paper were not altered in that update.

F. Public Comments

    Before and during the TRAC meetings, the Agency received comments 
on how to approach and improve its interim policies. Specifically, EPA 
received several petitions, including those from the National Food 
Processors Association, the Natural Resources Defense Council (NRDC) 
and others, a report from the Implementation Working Group (IWG), 
letters from the Environmental Working Group, and various 
correspondence from Congress and others. These documents will be 
considered as the Agency refines its science policies, and will also be 
made available through the public docket.
    1. NRDC petition. On April 23, 1998, the NRDC and various 
individuals and other public interest organizations filed a petition 
requesting that EPA issue an interpretive rule/policy statement 
regarding EPA's implementation of the FQPA provision concerning the 
additional ten-fold safety factor to protect infants and children. The 
petition seeks three specific actions:
    i. Issuance of a policy statement/interpretive rule providing that 
EPA maintain the ten-fold safety factor unless the Administrator has 
determined that there are reliable data on [evolving] prenatal and 
postnatal toxicity and exposure for fetuses, infants, and children. The 
petition sets forth a minimum set of data that petitioners believe 
constitutes ``reliable data'' and requests that the statement/rule 
direct EPA to apply the additional ten-fold factor if any of these data 
are absent.
    ii. Convene a ``blue ribbon panel'' to assist EPA in determining 
when there are reliable data for prenatal and postnatal toxicity to 
fetuses, infants, and children. NRDC recommends that this panel be 
convened under the auspices of the Children's Health Protection 
Advisory Committee.
    iii. Issuance of a policy statement/interpretive rule providing 
that, pending completion of the panel's report, EPA will apply the ten-
fold safety factor.
    2. Grower group and trade association petition. On May 26, 1998, 
EPA received a petition on rulemaking under the FQPA submitted on 
behalf of several grower groups and trade associations. The petition 
requested EPA to use notice and comment rulemaking to establish 
policies and procedures for implementing FQPA. The petitioners claimed 
that rules are needed to establish policies and procedures for 
determining when the FQPA ten-fold safety factor may be reduced or 
removed.
    3. IWG report. The IWG, a coalition of farm, food, manufacturing, 
and pest management organizations, issued a ``road map'' report on June 
18, 1998, which presents the IWG's views on how EPA can ensure what 
they regarded as a more balanced and workable implementation of FQPA. 
Their comments included the FQPA Safety Factor.

[[Page 37005]]

IV. Summary of FQPA Safety Factor Papers

A. Toxicology Data Requirements for Assessing Risks of Pesticide 
Exposure to Children's Health

    The Toxicology Working Group of the 10X Task Force has developed a 
report addressing the role of toxicology data requirements in assessing 
risks to children's health from pesticide exposure. Specifically, the 
report provides guidance on the use of toxicity data in hazard 
characterization and dose-response analysis relevant to decisions about 
the FQPA 10X Safety Factor.
    First, the report expands on the definition of prenatal and 
postnatal toxicity (developmental toxicity) from the EPA Guidelines for 
Developmental Toxicity Risk Assessment (1991), and recommends a core 
toxicology data set for conventional, food-use pesticides. In 
particular, the report suggests that adult and developmental 
neurotoxicity testing and adult immunotoxicity testing be included as a 
routine part of the core test data set for food-use pesticides because 
the current weight-of-the-evidence triggers may not identify all 
pesticides that have the potential to produce developmental 
neurotoxicity and immunotoxicity.
    The report then describes criteria for assessing the overall 
``degree of concern'' for children's health effects that encompasses a 
review of all available toxicity information. The recommended approach, 
which includes an evaluation of the degree of concern for children's 
health, represents an evolution and further harmonization of the 
approaches previously taken by EPA. The criteria for this approach fall 
into four basic categories, each of which the report discusses in 
detail:
    1. Human data on prenatal and postnatal toxicity.
    2. Prenatal and postnatal toxicity in animal studies.
    3. The dose-response nature of the experimental animal data.
    4. The relevance of the experimental animal data for humans.
    When a dose-response analysis is done for health effects of 
pesticides in general, the report recommends how a dose-response 
analysis should be performed for children's health effects. That is, 
the data on developmental toxicity should be evaluated along with the 
data on adult toxicity, and the No Observed Adverse Effect Level 
(NOAEL) for the more sensitive or critical effect levels should be 
based on consideration of all health effects observed. In doing so, 
children's health will be protected along with that of other sensitive 
populations.
    The report indicates that the default intraspecies ten-fold 
uncertainty factor, which is applied to account for variations in 
toxicity among humans, will be adequate in the majority of cases for 
protecting children's health regarding toxicity concerns, if a complete 
developmental toxicity data base is available. The report suggests that 
when data specific to children's health are missing or inadequate for a 
particular pesticide, application of the data base uncertainty factor 
in addition to the ten-fold intraspecies variability factor would 
account for the possibility that children may be significantly more 
sensitive than adults.
    Although the report asserts that there is no formal process for 
considering the degree of concern in the RfD determination, the report 
recognizes that some aspects of degree of concern are taken into 
account at this point in the risk assessment process, for example, when 
developmental effects are selected as the most sensitive endpoints. 
Nevertheless, the report recommends that this issue be further 
considered in the calculation of the RfD.
    In addition to the recommendations described above, the report 
makes several recommendations concerning the development of new data 
requirements:
    1. 40 CFR part 158.340 should be updated to include the adult and 
developmental neurotoxicity guidelines and the adult immunotoxicity 
guidelines and to refer to the newly revised two-generation 
reproduction and prenatal developmental toxicity testing guidelines.
    2. Guidelines for pharmacokinetic studies should be developed that 
include considerations of exposure during pregnancy and lactation, and 
of infants and children. These data can be developed as part of a 
tiered approach to overall pharmacokinetic evaluations and should be 
required for assessment of effects of pesticides on infants and 
children in 40 CFR part 158.
    3. Specific testing guidelines for other types of functional or 
latent effects (e.g., developmental immunotoxicity, developmentally-
induced cancer) do not currently exist. As well, guidelines for direct 
dosing of neonates and appropriate interpretation and application of 
such data are not available. Efforts should be made to develop these 
guidelines as well as criteria for when such studies should be 
conducted.

B. Exposure Data Requirements for Assessing Risks to Children's Health 
from Pesticide Exposure

    The Exposure Working Group of the 10X Task Force has developed a 
report addressing the role of exposure data requirements in assessing 
risks to children's health from pesticide exposure. The report gives 
information and describes general principles for conducting exposure 
assessments. It also discusses issues that are specific to conducting 
exposure assessments for children.
    The report contains criteria by which OPP evaluates data sets used 
in an exposure assessment. If direct measurements of exposure are used 
for the assessment, then the available exposure data must be of 
suficient quality and quantity to provide high confidence that the 
assessment will be protective of infants and children. If models are 
used to estimate exposure, then the exposure assumptions in the models 
must be judged to be conservative. The greater the uncertainty in the 
data associated with the assumptions, the more conservative (i.e., 
unlikely to underestimate exposure) the assumptions should be.
    Finally, the report describes the assessment procedures for 
estimating single pathway pesticide exposures from food, drinking 
water, and non-occupational sources. It also characterizes the types of 
data that are used in the assessments. For each pathway, the procedures 
and data are evaluated to determine if there is a high level of 
confidence that the assessment is protective of infants and children. 
The report lists a number of recommendations on how to improve the 
assessment procedures, mentions the ongoing work within EPA to improve 
the procedures, and addresses the issues associated with aggregating 
exposures from different sources.

C. The Office of Pesticide Programs' Guidance Document on the 
Determination of the Appropriate FQPA Safety Factor(s) for Use in the 
Setting of Tolerances

    The OPP guidance document describes the OPP policies for 
determining the appropriate FQPA Safety Factor(s) to apply when 
establishing, modifying, leaving in effect, or revoking a tolerance or 
exemption for a food use pesticide. It presents the legal framework for 
the FQPA Safety Factor and key interpretations of that framework. It 
states that, while the legislative language incorporates the term 
``safety factor'' instead of the term ``uncertainty

[[Page 37006]]

factor,'' OPP believes that Congress clearly intended the FQPA Safety 
Factor to address uncertainty resulting from incompleteness of data 
and, therefore, deems the statutory term to incorporate the 
``uncertainty factor'' concept. The document offers the opinion that 
the FQPA Safety Factor is to be applied in addition to the two routine 
or baseline factors which account for: (1) Differences in sensitivity 
and variability between humans (the ``intraspecies'' uncertainty 
factor) and (2) differences in sensitivity between experimental animals 
and humans, if animal data have been used as the basis for deriving the 
hazard values (the ``interspecies'' uncertainty factor). Therefore, the 
FQPA Safety Factor would include other uncertainty or modifying factors 
used in the calculation of hazard values, for example, the data base 
uncertainty factor that is applied when one or more critical core 
studies are missing.
    The document describes the set of pesticides for which FQPA Safety 
Factor determinations would be made primarily as food-use chemicals of 
``conventional'' chemistry for which hazard values such as the acute or 
chronic reference doses (RfD) can be derived. OPP would expect to make 
FQPA Safety Factor decisions when assessing risk to infants and 
children up through the time of sexual maturation, women of child-
bearing age, and on occasion, sexually mature males. FQPA Safety Factor 
recommendations will be made as the risk characterization is being 
developed; the final decision will be made during the risk management 
process.
    The guidance describes the criteria by which OPP determines the 
completeness of the toxicology data base for conducting a high quality 
hazard characterization. OPP makes this determination employing a 
weight-of-the-evidence approach. The core toxicology data base for a 
specific chemical generally consists of studies which meet three 
criteria:
    1. All studies in the core data base must have ``official'' testing 
guidelines or standard, well-documented protocols available.
    2. The studies will have been required under FIFRA/ FFDCA as first 
tier requirements or will have been triggered by results of Tier 1 or 
other existing studies (see the regulations in 40 CFR 158.340, subpart 
F). Alternatively, studies are required under a well-established policy 
and practice for registration and reregistration/renewal (e.g., data 
call-ins) and this requirement has resulted in the generation and 
submission of the data with which the Agency has acquired experience in 
evaluating.
    3. There is consensus in the scientific community that there is a 
body of evidence supporting the conclusion that the results of such 
studies significantly improve the understanding of the potential hazard 
of the pesticide to humans, including infants and children.
    The document notes that OPP will, in the next few months, propose 
to revise the toxicology data requirements in part 158, to include 
several new studies as Tier 1 requirements (e.g., the acute and 
subchronic neurotoxicity studies in adult mammals, the developmental 
neurotoxicity study, two immunotoxicity studies, and the 21-day dermal 
study) plus others as Tier 2 (i.e., conditionally required). In 
addition, there is a description of the criteria and other bases by 
which OPP has concluded that it is appropriate to begin the process to 
issue data call-ins for the acute and subchronic neurotoxicity studies 
in adult mammals and the developmental neurotoxicity study for a subset 
of conventional chemistry pesticides which are known neurotoxins.
    Separate from the question of what data will comprise a complete 
data base is the issue of what data base uncertainty factor should be 
applied when critical core studies are missing or inadequate. This 
document addresses this issue, including when the number of studies 
considered critical for a ``high confidence'' chronic RfD is expanded 
in the near term from five to six, and, then, after the studies are 
routinely required, received and understood, to eight. The data base 
uncertainty factor fulfills the same purpose as, and, in effect, 
becomes part of the FQPA Safety Factor. This guidance document 
incorporates the criteria and factors for assessing the degree of 
concern regarding the potential for prenatal and postnatal effects, as 
presented in the framework described in the report of the Toxicology 
Working Group of the Agency 10X Task Force entitled ``Toxicology Data 
Requirements for Assessing Risks of Pesticide Exposure to Children's 
Health.'' (Toxicology Working Group, 1999).
    The guidance document also considers the completeness of the 
toxicology data base and degree of concern in the selection and 
application of uncertainty factors when calculating the acute or 
chronic RfD and in the recommendations regarding the FQPA Safety 
Factor. The RfD derivation process takes into account deficiencies in 
the core toxicology data base and the potential for hazard to fetuses, 
infants and children (and, therefore, the degree of concern). The 
document articulates criteria for determining OPP's overall level of 
confidence in the hazard-related information and hazard assessment 
approaches employed. If, for some reason, an assessment does not meet 
this standard, then the assessment is said to contain ``residual 
uncertainties or concerns.'' Any residual concerns remaining after the 
hazard assessment is examined are dealt with when making the final FQPA 
Safety Factor decision(s). During the period after a determination is 
made to require new toxicology studies, but before they become part of 
the core toxicology data base, their absence is evaluated as part of 
``residual uncertainties or concern'' in the FQPA Safety Factor 
assessment process. This document states OPP's intention to solicit 
broad public input regarding the appropriate consideration of the 
absence of these particular newly-required studies in the FQPA Safety 
Factor assessment process.
    Just as for hazard potential, determination of the completeness of 
the exposure data base--in the context of aggregate exposure and risk 
assessment--is a primary consideration relative to the FQPA Safety 
Factor. As described in the report of the Exposure Working Group of the 
Agency 10X Task Force entitled ``Exposure Data Requirements for 
Assessing Risks of Pesticide Exposure to Children's Health'' (Exposure 
Working Group, 1999), OPP estimates exposure using chemical-specific 
and other reliable empirical data as well as models and conservative 
assumptions, which also are based upon reliable data. The Office is 
confident that, in the great majority of cases, it is not 
underestimating exposure to infants and children or to the general 
population. The guidance document acknowledges the desirability of 
obtaining more extensive and specific exposure data and notes that OPP 
continues to pursue the acquisition of such data from the private 
sector and its own and other agencies' research efforts. If any 
residual concerns remain after the exposure assessment is examined, 
these are dealt with when making the final FQPA Safety Factor 
decision(s). The guidance states that the absence of detailed and 
specific exposure data would require the application of an additional 
safety factor unless OPP can determine that the available data and its 
assessment methodologies give a high degree of confidence that exposure 
to infants and children is not underestimated. However, because OPP's 
approach to estimating exposure in the absence of extensive, specific 
data is typically very conservative, OPP can

[[Page 37007]]

usually conclude, with a high degree of confidence, that its approach 
adequately protects infants and children, and the FQPA Safety Factor 
would not be needed to address uncertainties in the exposure data base.

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    The guidance document notes that the decision, either that the 
default FQPA Safety Factor is to be applied or that there are reliable 
data which support the application of a different factor, uses a 
``weight-of-the-evidence'' approach. This approach simply means that 
all of the data with regard to both hazard and exposure are considered 
simultaneously as the total body of evidence with regard to the 
pesticide(s) being evaluated. The integration approach to evaluating 
the available hazard- and exposure-related information involves 
characterization of the overall confidence that infants and children 
will be protected. As illustrated in the figure above, the weight-of-
the-evidence considerations include the level of confidence in the 
hazard and exposure assessments, and whether or not there are any 
residual uncertainties identified in the risk characterization. If 
there is a high level of confidence that the combination of the hazard 
and exposure assessments is adequately protective of infants and 
children, then the default FQPA factor would not be applied at this 
stage in the process. For example, the optimal case would be one in 
which there is a high level of confidence that the hazard and exposure 
assessments are sufficiently conservative and there are no residual 
uncertainties in the assessment; then it would not be necessary to 
apply an additional safety factor to protect infants and children. At 
the other extreme is the case where OPP may find that reliable data do 
not support a particular finding other than to retain the 10X default 
factor, given the low level of confidence that the hazard and exposure 
assessments are sufficiently conservative and there are residual 
uncertainties that have not been dealt with in the assessment. 
Alternatively, in other cases where there is also a low level of 
confidence in the hazard and exposure assessments and residual concerns 
remain, an additional safety factor other than the 10X default (perhaps 
even greater) would be applied. The size of the final factor would 
depend on the overall weight-of-the-evidence and the level of 
confidence in the assessment.
    The recommendation concerning the FQPA factor is made based upon 
consideration of the nature and level of confidence in the hazard and 
exposure assessments, the degree of concern for potential hazard to the 
fetus, infants and children, and any residual uncertainties that are 
not accounted for in the hazard and exposure assessments. The final 
decision on the FQPA Factor is informed by the science presented in the 
risk characterization and the recommendation.

D. ``Standard Operating Procedures (SOP) for HED FQPA Safety Factor 
Committee''

    The Standard Operating Procedures (SOP) is a working level document 
designed to obtain and organize information from disciplinary review

[[Page 37008]]

scientists regarding the following: (1) The contribution of the hazard 
and dose response evaluations in determining whether an additional FQPA 
safety factor is required; (2) the contribution of the exposure 
assessment(s) in evaluating the safety factor; and (3) the 
characterization of both the toxicology and exposure data bases. The 
Committee considers this information in making the safety factor 
recommendation for each pesticide on a case-by-case basis using a 
weight-of-the-evidence approach. On December 9, 1998, the OPP FQPA 
Safety Factor Committee presented to the FIFRA Scientific Advisory 
Panel (SAP) its SOP for recommending the safety factor for risk 
assessments prepared in support of tolerance decisions. The Committee 
has revised its draft Standard Operating Procedures (SOP) in accordance 
with the draft OPP Policy Document and the recommendations of the SAP; 
the committee is issuing this revised document for comment today.

V. Questions/Issues for Comment

    Because the four science policy documents covered by this notice 
have many common issues, the Agency encourages the public to submit 
comments by issue or topic rather than for each separate document. To 
facilitate this approach to commenting, EPA has placed all four 
documents under the same docket number (see Unit I.C. of this 
document). In this way, commenters may efficiently address a science 
policy or other issues that are addressed in the different documents.
    Although EPA is making four documents concerning the FQPA 10X 
Safety Factor available for review and public comment, the Agency 
encourages the public to focus particularly on the OPP Guidance 
Document, ``The Office of Pesticide Programs' Policy on Determination 
of the Appropriate FQPA Safety Factor(s) for Use in the Tolerance-
Setting Process.'' While OPP used the two papers produced by the 
Toxicology and Exposure Working Groups of the Agency's 10X Task Force 
in developing its guidance, at this time, the 10X Task Force is not 
planning to revise and reissue these documents following public 
comment. In addition, the OPP Standard Operating Procedure is largely 
derived from the OPP Guidance Document, and any changes in it following 
public comment should reflect changes in the Guidance Document. 
Therefore, of the four documents being made available, OPP considers 
its Guidance Document the most important for the public to review and 
comment on.
    Following are several issues and associated questions for which EPA 
has particular interest in receiving comments:
General FQPA Safety Factor Issues
    1. The OPP Guidance indicates that OPP will generally apply the 
FQPA Safety Factor only to food-use pesticides of ``conventional'' 
chemistry. Please comment on this approach. The Guidance also indicates 
that different decisions about the need for, and size of, an additional 
FQPA Safety Factor may be appropriate for different durations of 
exposure and different exposed populations. Please comment on this 
approach. Finally, the Guidance indicates that it would be appropriate 
to make only one FQPA Safety Factor decision for a single population/
exposure period, even though such exposure might occur by different 
routes and pathways. Please comment on this approach.
    2. Is a weight-of-the-evidence approach to making FQPA Safety 
Factor decisions appropriate, taking into consideration the toxicology 
and exposure data bases for a pesticide and the potential risks for the 
developing fetus, infant and child as well as other populations? If 
not, why not? Given the scope of the evidence which OPP intends to 
consider, are there any other types of information that OPP should 
consider in making its FQPA Safety Factor determinations?
    3. Do you agree with the view that the models and assumptions used 
by OPP in the risk assessment process, together with reliable data 
available on specific pesticides and other reliable, empirical data, 
typically do not understate risk? If not, under what circumstances do 
you believe OPP's current approaches to assessing risks from aggregate 
exposure to a single pesticide produce risk assessments that understate 
the risks to infants and children?
    4. Do you agree with OPP's view that the FQPA Safety Factor should 
be applied in addition to the interspecies and intraspecies uncertainty 
factors, but that the FQPA Safety Factor should not be applied in a 
manner that results in ``double-counting'' of uncertainties that are 
otherwise addressed in the toxicity and exposure assessments through, 
for example, the data base uncertainty factor or conservative exposure 
models? If you disagree, why?
Toxicology Issues
    1. Please comment on OPP's proposed criteria for defining the core 
toxicology data base.
    2. After having considered the recommendations from the FIFRA 
Scientific Advisory Panel and the Toxicology Working Group, OPP is 
beginning the process of calling in data for three studies (the acute 
and subchronic neurotoxicity studies in adult mammals and the 
developmental neurotoxicity study) for a subset of conventional 
chemistry food-use pesticides known neurotoxicants. In addition, OPP 
will be proposing to require the same set of studies for all 
conventional chemistry food-use pesticides in the revision of the part 
158 regulations. Please comment on this two-stage approach.
    3. The OPP Policy Guidance indicates that one of the critical 
issues is whether or not to apply an FQPA Safety Factor pending receipt 
of newly-required studies. There are a variety of possible approaches. 
One possible approach would be to apply the FQPA Safety Factor's data 
base uncertainty component to gaps related to new core data 
requirements only where there are specific concerns regarding the 
pesticide pertaining to the data requirement. Alternatively, OPP could 
apply the default 10X factor (or some other additional factor) whenever 
a new data requirement is added and/or whenever a testing guideline is 
changed. Please explain how you think the FQPA Safety Factor provision 
should be implemented when OPP makes such changes. In commenting, 
please address whether OPP should apply the default FQPA 10X factor, 
some different yet additional factor, or no factor at all in the 
following circumstances:
    i. A minor change to testing guidelines.
    ii. A major change to testing guidelines.
    iii. An addition of a new required test.
    iv. An addition of a new required test to core requirements.
    4. In the absence of the results from any of the studies to be 
required through data call-in notices (i.e., the acute and subchronic 
neurotoxicity studies in adult mammals and the developmental 
neurotoxicity study), what information from existing studies on a 
specific chemical would increase or decrease the concerns about the 
potential for prenatal and postnatal hazard, in general, and for 
neurotoxicity and developmental neurotoxicity, in particular? Which, if 
any, of the seven criteria discussed in section V.A.1.a., footnote 4 
and associated text of the OPP Guidance document is appropriate for 
judging whether there is increased concern about the potential for a 
pesticide to cause developmental neurotoxicity? Are there any other 
criteria which would be useful for informing this judgment?
    5. Please comment on whether you would expect that developmental 
neurotoxicity studies would, for a

[[Page 37009]]

substantial number of chemicals, identify effects that are not detected 
in other studies and more fully characterize the potential risks of 
exposures during development. In addition, please comment on the 
sensitivity of these tests vis-a-vis other studies required and used 
for age-related comparisons for acute, intermediate, or chronic RfD 
derivation (e.g., prenatal developmental toxicity or multi-generation 
reproduction study, subchronic and chronic studies, etc.). Please 
explain the basis of your opinion.
    6. OPP's Guidance states that currently five studies (a multi-
generation reproduction study, prenatal developmental toxicity studies 
in two species, and chronic toxicity studies in a rodent and non-rodent 
species) comprise the toxicity data base necessary to produce a ``high 
confidence RfD,'' and that some additional data base uncertainty factor 
will be imposed if the data base on a pesticide lacks one or more of 
these studies. OPP proposes to expand this core data base to include 
the subchronic neurotoxicity study. Eventually, OPP also includes the 
acute neurotoxicity study in adult mammals and the developmental 
neurotoxicity study, once these studies have met the criteria for 
inclusion in the core toxicity data base. Please comment on OPP's 
proposed approach to imposing a data base uncertainty factor of 3x if 
one key study is missing from the data base and a factor of 10x if more 
than one is missing.
    7. OPP is proposing to adopt the framework and its criteria/factors 
for assessing the degree of concern about the potential for prenatal 
and postnatal effects as recommended by the Toxicology Working Group. 
Please comment on the appropriateness of the proposed criteria/factors 
for use in this assessment process, and OPP's proposed approach for 
accommodating its concerns in the Reference Dose derivation and FQPA 
Safety Factor decision processes, in the near term, and in the longer 
term.
    8. When the hazard to infants and children is well-characterized, 
and the data show that infants and/or children are more susceptible 
than adults, under what circumstances, if any, should this information 
lead OPP to employ an additional Safety Factor?
Exposure Issues
    1. Subject to the qualifications expressed in the OPP Policy 
document and the report from the Exposure Working Group, OPP believes 
that each of the tiers for estimating exposure to a pesticide through 
food, in almost all instances, will not underestimate exposure to 
infants and children. Please comment on this conclusion, as it applies 
to each of the tiers.
    2. OPP is developing a tiered approach to assessing the likelihood 
and magnitude of contamination of drinking water and its sources by a 
pesticide. As an interim approach, when direct assessment is not 
possible, is it reasonable and protective to regard the estimates 
generated by OPP's current screening methodology as upper bound 
pesticide concentrations for surface and ground water and to assume 
that this concentration generally will not be exceeded in drinking 
water?
    3. OPP is developing approaches to assess the likelihood and 
magnitude of exposure to pesticides in residential and other non-
occupational use scenarios. When direct assessment is not possible, is 
it reasonable and protective to regard the estimates of exposure for 
the major residential and other non-occupational exposure use scenarios 
developed by OPP as upper bound estimates of the exposure received by 
infants and children from such use?
    4. In OPP's view, its aggregate exposure assessments generally do 
not underestimate the exposure to infants and children because the 
aggregate exposure is calculated by adding the high-end estimates of 
exposure to pesticides in food, to the high-end estimates of exposure 
to pesticides both in water and as a consequence of pesticide use in 
residential and similar settings. Please comment on this view.

VI. Policies Not Rules

    The draft policy document discussed in this notice is intended to 
provide guidance to EPA personnel and decision-makers, and to the 
public. As a guidance document and not a rule, the policy in this 
guidance is not binding on either EPA or any outside parties. Although 
this guidance provides a starting point for EPA risk assessments, EPA 
will depart from its policy where the facts or circumstances warrant. 
In such cases, EPA will explain why a different course was taken. 
Similarly, outside parties remain free to assert that a policy is not 
appropriate for a specific pesticide or that the circumstances 
surrounding a specific risk assessment demonstrate that a policy should 
be abandoned.
    EPA has stated in this notice that it will make available revised 
guidance after consideration of public comment. Public comment is not 
being solicited for the purpose of converting any policy document into 
a binding rule. EPA will not be codifying this policy in the Code of 
Federal Regulations. EPA is soliciting public comment so that it can 
make fully informed decisions regarding the content of each guidance 
document.
    The ``revised'' guidance will not be unalterable. Once a 
``revised'' guidance document is issued, EPA will continue to treat it 
as guidance, not a rule. Accordingly, on a case-by-case basis, EPA will 
decide whether it is appropriate to depart from the guidance or to 
modify the overall approach in the guidance. In the course of inviting 
comment on each guidance document, EPA would welcome comments that 
specifically address how a guidance document can be structured so that 
it provides meaningful guidance without imposing binding requirements.

VII. Contents of Docket

    Documents that are referenced in this notice will be inserted in 
the docket under the docket control number ``OPP-00610.'' In addition, 
the documents referenced in the framework notice, which published in 
the Federal Register of October 29, 1998 (63 FR 58038) have also been 
inserted in the docket under docket control number OPP-00557.

List of Subjects

    Environmental protection, Administrative practice and procedure, 
Agricultural commodities, Pesticides and pests.

    Dated: June 30, 1999.
Susan H. Wayland,
Acting Assistant Administrator for Prevention, Pesticides and Toxic 
Substances.

[FR Doc. 99-17315 Filed 7-7-99; 8:45 am]
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