[Federal Register Volume 65, Number 127 (Friday, June 30, 2000)]
[Notices]
[Pages 40644-40650]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-16634]


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ENVIRONMENTAL PROTECTION AGENCY

[OPP-00658; FRL-6556-4]


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 are transparent and open to public 
participation, EPA is soliciting comments on the pesticide draft 
science policy paper entitled ``Proposed Guidance on Cumulative Risk 
Assessment of Pesticide Chemicals That Have a Common Mechanism of 
Toxicity.'' This document is the eighteenth in a series concerning 
science policy papers related to the Food Quality Protection Act and 
the Tolerance Reassessment Advisory Committee.

DATES: Comments for the draft science policy paper, identified by 
docket control number OPP-00658, must be received on or before August 
28, 2000.

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 the ``SUPPLEMENTARY INFORMATION.'' To ensure 
proper receipt by EPA, it is imperative that you identify docket 
control number OPP-00658 in the subject line on the first page of your 
response.

FOR FURTHER INFORMATION CONTACT: Kathleen Martin, Environmental 
Protection Agency (7509C), 1200 Pennsylvania, Ave., NW., Washington, DC 
20460; telephone number: (703) 308-2857; fax: (703) 305-5147; e-mail: 
[email protected].

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

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

[[Page 40645]]



 
------------------------------------------------------------------------
                                                         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. The 
North American Industrial Classification System (NAICS) codes have been 
provided to assist you and others in determining whether or not this 
action affects certain entities. If you have any questions regarding 
the applicability of this action to a particular entity, consult the 
person listed under ``FOR FURTHER INFORMATION CONTACT.''

B. How Can I Get Additional Information, Including Copies of this 
Document or Other Related Documents?

    1. Electronically. You may obtain electronic copies of this 
document, the draft science policy paper, and certain other related 
documents that might be available from the Office of Pesticide 
Programs' Home Page at http://www.epa.gov/pesticides. On the Office of 
Pesticide Programs' Home Page select ``FQPA'' and then look up the 
entry for this document under ``Science Policies.'' You can also go 
directly to the listings at the EPA Home Page at http://www.epa.gov. On 
the Home Page select ``Laws and Regulations'' and then look up the 
entry for this document under ``Federal Register--Environmental 
Documents.'' You can go directly to the Federal Register listings 
http://www.epa.gov/fedrgstr.
    2. Fax-on-demand. You may request a faxed copy of the draft science 
policy paper, as well as supporting information, by using a faxphone to 
call (202) 401-0527. Select item 6049 for the paper entitled ``Proposed 
Guidance on Cumulative Risk Assessment of Pesticide Chemicals That Have 
a Common Mechanism of Toxicity.'' You may also follow the automated 
menu.
    3. In person. The Agency has established an official record for 
this action under docket control number OPP-00658. In addition, the 
documents referenced in the framework notice, which published in the 
Federal Register on October 29, 1998 (63 FR 58038) (FRL-6041-5) have 
also been inserted in the docket under docket control number OPP-00658. 
The official record consists of the documents specifically referenced 
in this action, and other information related to this action, including 
any information claimed as Confidential Business Information (CBI). 
This official record includes the documents that are physically located 
in the docket, as well as the documents that are referenced in those 
documents. The public version of the official record does not include 
any information claimed as CBI. The public version of the official 
record, which includes printed, paper versions of any electronic 
comments submitted during an applicable comment period is available for 
inspection in the Public Information and Records Integrity Branch 
(PIRIB), Rm. 119, Crystal Mall #2, 1921 Jefferson Davis Hwy., 
Arlington, VA, from 8:30 a.m. to 4 p.m., Monday through Friday, 
excluding legal holidays. The PIRIB 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-00658 in the subject line on the 
first page of your response.
    1. By mail. Submit your comments to: Public Information and Records 
Integrity Branch (PIRIB), Information Resources and Services Division 
(7502C), Office of Pesticide Programs (OPP), Environmental Protection 
Agency, 1200 Pennsylvania, Ave., NW., Washington, DC 20460.
    2. In person or by courier. Deliver your comments to: Public 
Information and Records Integrity Branch (PIRIB), Information Resources 
and Services Division (7502C), Office of Pesticide Programs (OPP), 
Environmental Protection Agency, Rm. 119, Crystal Mall #2, 1921 
Jefferson Davis Highway, Arlington, VA. The PIRIB is open from 8 a.m. 
to 4 p.m., Monday through Friday, excluding legal holidays. The PIRIB 
telephone number is (703) 305-5805.
    3. Electronically. You may submit your comments electronically by 
e-mail to: [email protected], or you can submit a computer disk as 
described above. Do not submit any information electronically that you 
consider to be CBI. Avoid the use of special characters and any form of 
encryption. Electronic submissions will be accepted in WordPerfect 6.1/
8.0 or ASCII file format. All comments in electronic form must be 
identified by docket control number OPP-00658. Electronic comments may 
also be filed online at many Federal Depository Libraries.

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

    Do not submit any information electronically that you consider to 
be CBI. You may claim information that you submit to EPA 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 the information claimed as 
CBI must be submitted for inclusion in the public version of the 
official record. Information not marked confidential will be included 
in the public version of the official record without prior notice. If 
you have any questions about CBI or the procedures for claiming CBI, 
please consult the person identified under ``FOR FURTHER INFORMATION 
CONTACT.''

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

    EPA invites you to provide your views on the various draft science 
policy papers, new approaches we have 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 
document.
    8. To ensure proper receipt by EPA, be sure to identify docket 
control number OPP-00658 in the subject line on the first page of your 
response. You may also provide the name, date, and Federal Register 
citation.

[[Page 40646]]

II. Background Information About the Tolerance Reassessment 
Advisory Committee

    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 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 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 worked with the 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.
    The TRAC identified nine science policy issue areas they believed 
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 
document published in the Federal Register of October 29, 1998 (63 FR 
58038), EPA has been issuing a series of draft papers concerning nine 
science policy issues identified by the TRAC related to the 
implementation of FQPA. This document announces the availability of the 
draft science policy paper(s) as identified in the ``SUMMARY.''

III. Summary of ``Proposed Guidance on Cumulative Risk Assessment 
of Pesticide Chemicals That Have a Common Mechanism of Toxicity''

    The Food Quality Protection Act of 1996 requires EPA to consider 
the cumulative effects to human health that can result from exposure to 
pesticides and other substances that have a common mechanism of 
toxicity. This document describes the process that OPP is developing 
for performing cumulative risk assessments. Such assessments will play 
a significant role in the evaluation of risks posed by pesticides, and 
will enable OPP to make regulatory decisions that fully protect public 
health and sensitive subpopulations, including infants and children.
    The cumulative assessment of risk posed by exposure to multiple 
chemicals by multiple pathways (including food, drinking water, as well 
as from residential/non-occupational exposure to air, soil, grass, and 
indoor surfaces) presents a formidable challenge for OPP. Given that 
cumulative risk assessment is at an early phase of development, and 
will continue to evolve with experience and improved toxicological and 
exposure databases, the goal of this draft science policy paper is to 
describe the first generation of methods and approaches to the 
cumulative risk assessment process. Thus, this guidance for cumulative 
assessment should be viewed as a work in progress.
    Before undertaking a cumulative risk assessment for a set of 
chemicals that have a common mechanism of toxicity, OPP will follow its 
procedures for identifying the chemicals that belong in that group (see 
``Guidance for Identifying Pesticide Chemicals and Other Substances 
that Have a Common Mechanism of Toxicity,'' 64 FR 5796, February 5, 
1999 (FRL-6060-7); also see OPP's Home Page at http://www.epa.gov/pesticides). This process involves the use of a weight-of-the-evidence 
approach to identify a list of candidate chemicals, a ``Common 
Mechanism Group'' (CMG), for which scientifically reliable data 
demonstrate a common toxic effect by a common mechanism of action.
    Also before conducting a cumulative assessment, OPP will perform an 
aggregate risk assessment for each chemical in a CMG. OPP will follow 
the guidance described in the draft science policy paper entitled, 
``Guidance for Performing Aggregate Exposure and Risk Assessments,'' 
which was issued for public comment on November 10, 1999 (64 FR 61343) 
(FRL-6388-8); also see OPP's Home Page at http://www.epa.gov/pesticides). Using this guidance, OPP will simultaneously consider the 
exposures from dietary (food), drinking water, and residential/non-
occupational uses of each pesticide. If the combined exposure from 
these sources exceeds the level of concern, then OPP would take 
appropriate regulatory action.
    When the aggregate risk assessments for individual chemicals in a 
CMG are completed, OPP will perform the cumulative risk assessment in 
the four steps summarized below: (1) Hazard assessment and 
characterization; (2) Dose response assessment and characterization; 
(3) Exposure assessment and characterization; and (4) Risk 
characterization. OPP will carry out steps 1 and 2 by using a weight-
of-the-evidence approach to determine the toxic endpoint that occurs 
through a common mechanism for the chemicals in the CMG, and by 
establishing a common measure of toxic potency (``common point-of-
departure'') on which the cumulative risk assessment is based. For 
steps 3 and 4, OPP will estimate exposure and risks for the dietary 
(food), residential/non-occupational and drinking water pathways. 
However, due to limitations

[[Page 40647]]

in currently available data and assessment methodologies, OPP will 
usually not be able to simply add exposures across these pathways. 
While OPP has extensive data for dietary (food) exposures, the data for 
residential/non-occupational and drinking water exposure are 
comparatively less. OPP is working to improve its ability to develop 
better estimates of exposure both through drinking water and from 
residential use. For example, OPP is exploring the use of surrogate/
bridging data for pesticides with similar use patterns that can be used 
to estimate residential exposures that are similarly descriptive as the 
dietary exposure assessment. This approach is comparable to the 
approach currently used for worker exposure assessments using the 
Pesticide Handlers' Exposure Database (PHED) where data from different 
pesticides with similar use patterns are used to estimate likely 
exposures to other pesticides. In fact, OPP is currently developing a 
pilot cumulative assessment on a set of organophosphates (OPs). OPP 
plans to present this assessment to the SAP for review/comment when 
completed. The assessment will provide tangible examples of how 
surrogate/bridging data may be used in such an assessment. Lessons 
learned from this use of surrogate data will be used to update this 
guidance in the future.
    When data on and methods for estimating exposure by different 
pathways--food, drinking water, residential use--are of appropriate 
quality, OPP will combine exposure estimates for a quantitative, 
cumulative risk assessment. In other circumstances, however, OPP can 
perform sophisticated, refined probabilistic exposure and risk 
assessments for food exposure, but may only be able to conduct single-
point (``deterministic'') exposure and risk assessments for non-
occupational exposures, and screening level modeling estimates for 
potential drinking water exposures. Hence, OPP does not believe that it 
is scientifically appropriate in most cases to add exposures across 
these pathways to obtain a cumulative total. Nevertheless, OPP will 
consider the exposures and risks from all pathways ``in parallel'' and 
at a minimum will develop comparative qualitative assessments in order 
to complete the cumulative assessment and to help inform what 
regulatory action may be necessary to assure the full protection of 
human health.
    It is OPP's goal to be able to combine exposures across all 
pathways as soon as scientifically reliable data and methodologies are 
available to do so. Toward this end, the Agency is making a concerted 
effort to develop or obtain new data and more sophisticated exposure 
and risk assessment methodologies. EPA's Office of Research and 
Development is planning and conducting new studies concerning exposure 
to infants and children related to non-occupational routes of exposure. 
OPP has also called in data from registrants for several non-dietary 
routes of exposure including dermal contact and hand/object-to-mouth 
contact with contaminated surfaces and toys. OPP is also working 
collaboratively with the U.S. Geological Survey to develop new 
regression-based, predictive modeling tools which OPP expects will 
allow for improved estimates of pesticide concentrations in finished 
drinking water. And many registrants are conducting studies on their 
own initiative that are generating additional exposure data for food, 
drinking water, and residential/non-occupational sources. Moreover, OPP 
is continuously developing and proposing through its science policies 
better methods for assessing exposure and risk. Finally, through 
publication of this draft science policy paper and others, OPP is 
seeking ideas, feedback, and recommendations from the SAP and the 
general public.
    The guidance in this draft science policy paper lays down the 
following approaches and steps:
    1. Hazard assessment and characterization. Hazard assessment and 
characterization emphasizes the analysis and integration of all 
relevant biological information in selecting the toxicological endpoint 
upon which to base the accumulation of the common hazard across 
multiple chemicals sharing a common mechanism of toxicity.
    (a) Weight-of-the-evidence. A weight-of-the-evidence narrative 
should be included in the hazard characterization that clearly lays out 
a summary of the key evidence, describes the robustness of the data for 
characterizing the common mechanism of toxicity for each chemical 
member, characterizes the conditions under which the cumulative hazard 
may be expressed by route, pattern, duration and magnitude of exposure, 
and recommend the appropriate common toxicological endpoint(s) for 
dose-response assessment. Significant strengths, weaknesses, and 
uncertainties of the evidence are highlighted.
    (b) Common mechanism group. A common mechanism group (CMG) is a 
group of pesticides determined to cause adverse effects by a common 
mechanism of toxicity. The CMG is defined using the previously released 
``Guidance for Identifying Pesticide Chemicals and Other Substances 
that Have a Common Mechanism of Toxicity'' (64 FR 5796, February 5, 
1999). Not all members of a CMG will necessarily be incorporated in the 
cumulative risk assessment.
    2. Dose-response assessment and characterization. Dose-response 
assessment and characterization should provide a common and uniform 
basis for reliably determining each chemical member's relative toxic 
strength and contribution to the cumulative risk. For the common toxic 
endpoint, all dose-response assessments should include consideration of 
their relevance to assessing children's health risks by addressing 
whether key studies reflected dosing of adult age animals only.
    (a) Common point of departure. A common point of departure (POD) on 
each chemical's dose-response curve is identified to determine its 
toxic potency relative to the other chemical members. This point of 
departure should be based on a common endpoint which is derived from 
studies using the same species/strain/sex and duration of exposure for 
each chemical member in the group. Thus, previous chemical-specific 
assessments and resulting reference doses may be inappropriate because 
they may be based on a different endpoint, strain, or duration of 
exposure.
    (b) Benchmark response or effective dose. A common benchmark 
response or effective dose (ED) is the preferred point of departure to 
represent cumulative risk of the chemical group. Despite its 
limitations, the no-observed-adverse-effect-levels (NOAEL) will 
generally be used in the near term in many situations until the 
toxicological databases improve and permit reliable benchmark analysis.
    (c) Benchmark response or NOAEL. After a benchmark response or 
NOAEL is designated for an individual chemical member, there may be 
chemical specific adjustments needed to normalize the response data 
across the chemical group to ensure a more nearly uniform point of 
departure.
    (d) Dose addition approaches. Dose addition approaches are most 
appropriate to use for summing the cumulative hazard given that 
cumulative risk assessment will be based on chemicals sharing a common 
toxic effect that arises by a common mechanism of toxicity. Dose 
addition assumes that the chemicals of interest act on similar 
biological systems, behave similarly in terms of the primary 
physiologic processes (absorption,

[[Page 40648]]

metabolism, distribution, elimination), and elicit a common response. 
Thus, the cumulative margin of exposure approach or the relative 
potency factor approach are appropriate risk metric methods for 
normalizing exposure by accounting for the different relative toxic 
potencies of the group.
    3. Exposure assessment and characterization. Exposure assessment 
and characterization for the cumulative risk assessment will, to the 
extent data permit, maintain the temporal and spatial linkages for the 
many factors defining a possible individual exposure. The assessment 
will be designed in cooperation with the risk manager to assure that 
all necessary questions regarding potential risk are answered, but that 
the assessment performed is consistent with the data available.
    (a) Aggregate assessment. An aggregate assessment will be performed 
on each chemical that may be included in the cumulative risk assessment 
before the final assessment is designed. This step will ensure that the 
available data have been carefully evaluated with regard to their 
ability to describe the potential exposure of the population of 
interest to each chemical.
    (b) Focus on the major contributors to risk. The cumulative 
assessment will focus on the major contributors to risk, permitting 
resources and risk mitigation activities to be developed that will most 
efficiently address likely risk reductions.
    (c) Data and exposure assessment methods' availability and quality. 
Data and exposure assessment methods' availability and quality will 
also influence how comprehensive and refined an assessment can be 
performed. Data that lend themselves to distributional analyses should 
be used accordingly. Data that are less descriptive of the full range 
of potential exposures may be used in less comprehensive analyses. 
Where the quality of available data about exposure by different 
pathways varies greatly, cumulative assessments for individual pathways 
should be performed, but the exposure estimates for different pathways 
should not be combined quantitatively unless bridging data (surrogate 
data) are available. At a minimum, a qualitative assessment should be 
developed which covers topics such as comparative pathway analysis, 
high end exposure, variability, and uncertainty.
    4. Risk characterization. The risk characterization contains the 
primary conclusions regarding the character and potential magnitude of 
the cumulative risk. Included in the characterization is a discussion 
of how well the data support the conclusions as well as identification 
of key uncertainties and uses of assumptions. The major chemical 
contributors to the cumulative risk, the scenarios of concern, and 
subpopulations of special concern including children, are also 
identified.
    (a) A cumulative assessment group (CAG) is a subset of the CMG. The 
CAG is that group of pesticides selected for inclusion in the 
cumulative risk assessment. The chemicals in the CAG are judged to have 
a hazard and exposure potential that could result in the expression of 
a cumulative risk. Consideration of concurrent exposure is much greater 
for acute or short-term toxic effects because of the greater potential 
for more rapid onset of and recovery from the toxic effect. For chronic 
and cancer effects mediated through reversible precursor events, 
overlapping exposure should also be considered. For other chronic and 
cancer endpoints for which long-term exposure is necessary to cause the 
effect, concurrent exposures are not required for the chemicals to act 
by a common mechanism. Because of EPA's commitment to addressing those 
risks eliciting the greatest concern first, pesticides with essentially 
no exposure (as indicated by the single pesticide aggregate assessment) 
will be deferred from the CAG.
    (b) The outcome of a cumulative risk assessment is viewed as 
important information that will help inform risk management decisions 
regarding possible mitigation options across all members of the CAG.
    (c) There will not be one outcome but varying risk values for 
differing proportions of populations exposed to chances of adverse 
health effects resulting from different time scales of exposures.
    (d) A composite group uncertainty factor is applied after 
estimating cumulative risk to account for inter-species and intra-
species differences as well as uncertainties that are common and 
inherent to the chemical group.
    In September 1999, EPA presented a preliminary draft of the hazard 
and dose response components of the draft science policy paper for 
review by the FIFRA SAP. The purpose of that review was to seek early 
comment from the SAP on the hazard and dose response analyses needed 
when accumulating risk from exposure to two or more chemicals that 
share a common mechanism of toxicity (i.e., guidance contained in 
chapters 3 and 5 of the draft science policy paper). The issues covered 
at the September SAP meeting included selection of chemicals, common 
end pont, and a point of departure; methods for estimating the 
cumulative effect of a common mechanism; and how to deal with 
uncertainty. Additionally, a preliminary case study was presented on 
organophosphorus pesticides illustrating the hazard and dose-response 
guidance. In November 1999, the SAP provided EPA comments on the 
September draft. A draft of chapters 4 and 6 of the draft science 
policy paper was also taken to the SAP in December 1999, for discussion 
of exposure and risk characterization components of this guidance 
document. The SAP's comments on the December draft were completed in 
February 2000. After the SAP comments and the public comments on the 
draft science policy paper are received and reviewed by the Agency, it 
will be reissued in a revised form for use within and outside of OPP.
    The draft science policy paper discussed in this document 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.

IV. Questions/Issues

    OPP invites public comment on the following issues and questions:

A. Issue 1. Selection of Chemicals for a Cumulative Risk Assessment

    Chapter 3 of the draft science policy paper emphasizes that all 
chemicals which have been initially grouped by a common mechanism of 
toxicity are not necessarily appropriate for inclusion in a final 
cumulative risk assessment. There are both hazard and exposure 
considerations.
    Question 1: Does chapter 3 clearly present additional hazard 
considerations that are needed to determine those chemical members 
which should be included in the final cumulative risk assessment?

B. Issue 2. Selection, Normalization, and Adjustment of the Point of 
Departure (PoD) for Cumulating the Common Toxicity

    As discussed in chapter 5.1-5.2, a point of departure (i.e., a dose 
or

[[Page 40649]]

exposure metric corresponding to some fixed marker of toxicity) should 
be selected to sum the combined exposure for the chemical group. To the 
extent possible, the PoDs should reflect a uniform measure of the 
common toxic effect, which is produced by a common mechanism of 
toxicity, across the chemical members. A benchmark dose approach is 
preferred to derive the PoDs for each chemical member.
    Question 2: In single chemical assessments, the Agency uses the 
upper bound estimates (i.e., the lower confidence limit on dose) for 
both cancer (called LED) and noncancer benchmark dose assessment. The 
concern has been raised, however, that summing upper bounds of multiple 
compounds may result in a exaggerated risk. Do you agree that it is 
more appropriate to sum the central estimates (i.e., ED) rather than 
combining upper bounds in the cumulative risk assessment of multiple 
chemicals? If not, why not?

C. Issue 3. Incorporation of Group Uncertainty Factors

    As discussed in chapter 5.3, traditionally one or more of the 
uncertainty factors (UF) are used to derive a Reference Dose (RfD) for 
a single chemical. There are five uncertainty factors that are 
considered to account for the following extrapolations: LOAEL to NOAEL 
(UFL), subchronic NOAEL to chronic NOAEL (UFS), experimental animal to 
humans (UFA), interhuman variation (UFH), and incomplete database to 
complete database (UFD). It is proposed that the extrapolations of 
LOAELs to NOAELs or subchronic NOAELs to chronic NOAELs be applied as 
adjustments of a chemical's PoD before estimating the cumulative risk. 
These adjustments are meant to be based on some scientific data that 
permits a reasonable extrapolation or interpolation rather than applied 
solely as a science policy default decision. EPA further proposes that 
other traditional uncertainty factors be treated as a composite ``group 
uncertainty factor'' that pertains to the chemical members as a whole. 
Thus, the intra-species and inter-species UFs and the database 
completeness UF are applied as a composite group factor after 
cumulative risk is estimated (i.e., not before on each chemical's PoD). 
The rationale of the group UF is based on the premise that these 
factors should be viewed for the group as a whole given that all the 
chemicals are anchored by a common toxic effect produced by a common 
mechanism. Additionally, one is not simply evaluating risk in the 
context of a single chemical data base but the database for all the 
chemicals in the assessment. The advantage of a group uncertainty 
factor is that it allows one to separate the resulting risk that is 
based on scientific adjustments from judgmental policy decisions to 
account for uncertainty. Finally, EPA proposes that an FQPA safety 
factor decision be applied for the group rather than on individual 
pesticides.
    Question 3: Do you agree with this approach, and does the draft 
science policy paper clearly describe the rationale and guidance for 
the implementation of chemical specific adjustment factors and of a 
group UF for the cumulative risk assessment? Has the draft guidance 
clearly presented the limitations and strengths of the group UF 
approach?

D. Issue 4. Methods for Estimating the Cumulative Toxicity

    As discussed in chapter 5.6, one of the steps in the cumulative 
risk assessment process will be to select a method to cumulate dose or 
exposures. This method will serve to normalize differences in the toxic 
potencies among the chemicals in the cumulative assessment. Precedence 
in the Agency's 1986 and revised 1999 ``Guidance for Conducting Health 
Risk Assessment of Chemical Mixtures'' (http://www.epa.gov/ncea/pdfs/mixtures.pdf) describes several techniques for estimating risk to 
multiple chemicals. The cumulative guidance focuses on the component-
based dose addition methods used in the EPA's chemical mixture 
assessment guidance document. Two methods, a margin-of-exposure 
approach and an approach using relative potency factors, are presented.
    Question 4a: Do you agree that both methods are valid to consider 
for estimating cumulative risk associated with exposures to chemical 
that cause a common toxic effect by a common mechanism? Has the draft 
document clearly described these two approaches and their strengths and 
limitations? Are there other methods that OPP should consider?
    Question 4b: EPA anticipates that most mechanisms of toxicity 
encountered currently will be nonlinear dose-response relationships. 
Nevertheless, for mechanisms of toxicity consistent with linear dose-
response relationships, do you agree that using the relative potency 
factor approach by summing the slopes of the dose-response curves is an 
appropriate method? If not, what methods would you recommend for low-
dose linear extrapolations of risk?

E. Issue 5. Case Study

    In Appendix A of the draft science policy paper is a case study on 
organophosphorus pesticides.
    Question 5: Does this case study provide a clear example of the 
application of the hazard and dose-response elements of the draft 
guidance?

F. Issue 6. Input Parameters

    There are several types of data available for pesticide exposure 
assessment (e.g., field trial data, monitoring data, percent crop 
treated, label usage). For the food pathway, monitoring data are 
available from the USDA Pesticide Data Program (PDP). OPP conducts the 
majority of its drinking water assessments by calculating a screening 
level value. Similarly, residential assessments are conducted using the 
draft residential Standard Operating Procedures (SOPs) which also 
provide a screening level assessment. Thus, given PDP, the assessment 
of the food pathway will, in many cases, be based on higher quality 
data than for the residential and drinking water pathways where usually 
only screening values are available. Because of the different quality 
of data that will be encountered when conducting a cumulative exposure 
assessment, the concern is raised that the value and benefit of high 
quality monitoring data will be lost if combined with extrapolated 
exposure values from screening models.
    Question 6.1: Please comment on how this concern could be 
addressed. For instance, should OPP at this time conduct separate 
pathway assessments for food, drinking water, and residential exposures 
so as to avoid combining higher quality monitoring data with more 
limited screening level data?
    Question 6.2: Please comment on whether there are other means of 
dealing with existing data to reduce the uncertainties about exposure 
values derived from screening approaches.
    Question 6.3: Please comment on whether and how OPP could 
incorporate quantitative uncertainty analyses in the overal cumulative 
risk assessment when OPP uses data of varying quality.
    Question 6.4: Is it appropriate to extrapolate food exposure from 
residue field trials and use/usage information if food monitoring data 
such as USDA's PDP data are not available?

G. Issue 7. Deferral Criteria

    OPP is proposing that deferral criteria be applied to 
``negligible'' sources of risk in a full cumulative risk assessment. 
OPP believes that this

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approach will permit a better focus on the more important sources of 
risk. It will also assist the risk manager in understanding and 
evaluating sources of risk that may provide the greatest benefit with 
risk mitigation activities.
    Question 7.1: Please comment on whether the deferral criteria 
discussed in chapters 4 and 6 appear to be reasonable. Are there other 
exclusionary criteria that should be considered?
    Question 7.2: Should OPP establish more specific criteria, for 
example, not only the magnitude of the exposure resulting from a 
particular chemical, use pattern or pathway, but also the size of the 
exposed population group?

H. Issue 8: National and Regional Exposures

    The potential for people to encounter overlapping exposures to 
different pesticides will be influenced by many factors. One important 
consideration is the geographic effects and seasonal uses of 
pesticides. Thus, a framework is proposed for assessing different 
pathways of exposure that are essentially driven by these 
considerations. OPP believes that the food pathway should be approached 
on both a national and regional scale to account for both national and 
regional distribution of treated commodities. However, the OPP believes 
that residential and drinking water pathways are more appropriately 
dealt with on a regional or multi-state basis, since there is no 
single, national source of drinking water; and residential exposures 
may be driven by regional use patterns.
    Question 8.1: Please comment on whether the concept of developing a 
series of cumulative assessments on a geographic scale for different 
pathways is reasonable.

I. Issue 9: Case Study

    Cumulative risk assessment is at an early stage of development. 
Furthermore, there is very limited experience in conducting such 
assessments. Thus, the development of case studies using actual data 
are critical to refining useful and practical guidance, and to 
identifying future research and testing needs. OPP is taking a step 
wise approach to the development of such case studies by starting with 
simple examples and moving toward more complex situations.
    Attached is a case study that uses actual food residue data on 
three pesticides and evaluates only a single pathway/route/duration of 
exposure. Certain assumptions were made in the case study. In single 
chemical exposure assessment, for example, nondetects are assumed to be 
one half the level of detection and composite samples are decomposited. 
In this case study, for illustrative purposes, nondetects were assumed 
to be zero, the samples were not decomposited, and surrogate data were 
not used.
    Question 9.1: Given that an important goal of the cumulative 
assessment is to reliably determine sources of concern from a multi-
chemical exposure, please comment on to what extent is it appropriate 
to apply standard practices and assumptions used in single chemical 
assessments.

V. Policies Not Rules

    The draft science policy paper discussed in this document 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 document 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.

List of Subjects

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

    Dated: June 22, 2000.
Susan H. Wayland,
Acting Assistant Administrator for Prevention, Pesticides and Toxic 
Substances.
[FR Doc. 00-16634 Filed 6-29-00; 8:45 am]
BILLING CODE 6560-50-F