[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]]
_______________________________________________________________________
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]]
-----------------------------------------------------------------------
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.
-----------------------------------------------------------------------
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:
fenner-crisp.penelope@epa.gov.
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: opp-docket@epa.gov. 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.
BILLING CODE 6560-50-F
[GRAPHIC] [TIFF OMITTED] TN08JY99.006
BILLING CODE 6560-50-C
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]
BILLING CODE 6560-50-F
