[Federal Register Volume 67, Number 11 (Wednesday, January 16, 2002)]
[Notices]
[Pages 2210-2214]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-959]
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ENVIRONMENTAL PROTECTION AGENCY
[OPP-00658B; FRL-6814-3]
Pesticides; Guidance on Cumulative Risk Assessment of Pesticide
Chemicals That Have a Common Mechanism of Toxicity
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice of availability.
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[[Page 2211]]
SUMMARY: EPA announces the availability of the revised version of the
pesticide science policy document entitled ``Guidance on Cumulative
Risk Assessment of Pesticide Chemicals That Have a Common Mechanism of
Toxicity.'' This notice is one in a series of science policy documents
related to the implementation of the Federal Food, Drug, and Cosmetic
Act (FFDCA), as amended by the Food Quality Protection Act of 1996
(FQPA).
FOR FURTHER INFORMATION CONTACT: Beth Doyle, Environmental Protection
Agency (7503C), 1200 Pennsylvania Ave., NW., Washington, DC 20460;
telephone number: (703) 305-2722; fax number: (703) 305-0871; e-mail
address: [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:
------------------------------------------------------------------------
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
notice 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 science policy documents, 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,'' ``Regulations and
Proposed Rules,'' and then look up the entry to this document under
``Federal Register--Environmental Documents.'' You can go directly to
the Federal Register listings at http://www.epa.gov/fedrgstr.
2. In person. The Agency has established an official record for
this action under docket control number OPP-00658B. 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) under
docket control number OPP-00557, are considered as part of the official
record for this action under docket control number OPP-00658B even
though not placed in the official record. 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.
II. Background Information
On August 3, 1996, FQPA was signed into law. The FQPA significantly
amended the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA)
and 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 and strengthened health protections for infants and children
from pesticide risks.
Thereafter, 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 the broad policy
choices facing the Agency and on strategic direction for the Office of
Pesticide Programs (OPP). The Agency has used the interim approaches
developed through discussions with FSAC to make regulatory decisions
that meet the new FFDCA standard, but that could be revisited if
additional information became available or as the science evolved. In
addition, the Agency seeks independent review and public participation,
generally 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.
During 1998 and 1999, EPA and the U.S. Department of Agriculture
(USDA) established a second subcommittee of NACEPT, the Tolerance
Reassessment Advisory Committee (TRAC) to address FFDCA issues and
implementation. TRAC comprised more than 50 representatives of affected
user, producer, consumer, public health, environmental, states, and
other interested groups. The TRAC met from May 27, 1998, through April
29, 1999.
In order to continue the constructive discussions about FFDCA, EPA
and USDA have established, under the auspices of NACEPT, the Committee
to Advise on Reassessment and Transition (CARAT). The CARAT provides a
forum for a broad spectrum of stakeholders to consult with and advise
the Agency and the Secretary of Agriculture on pest and pesticide
management transition issues related to the tolerance reassessment
process. The CARAT is intended to further the valuable work initiated
by the FSAC and TRAC toward the use of sound science and greater
transparency in regulatory decisionmaking, increased stakeholder
participation, and reasonable transition strategies that reduce risks
without jeopardizing American agriculture and farm communities.
As a result of the 1998 and 1999 TRAC process, EPA decided that the
implementation process and related policies would benefit from
providing notice and comment on major science policy issues. The TRAC
identified nine science policy areas it believed were key to
implementation of tolerance reassessment. EPA agreed to provide one or
more documents for comment on each of the nine issues by announcing
their availability in the Federal Register. In a notice published in
the Federal Register of October 29, 1998 (63 FR 58038) (FRL-6041-5),
EPA described its intended approach. Since then, EPA has been issuing a
series of draft documents concerning the nine science policy issues.
This notice announces the availability of the revised science policy
[[Page 2212]]
document concerning cumulative risk assessment.
III. Summary of ``Guidance on Cumulative Risk Assessment of
Pesticide Chemicals That Have a Common Mechanism of Toxicity''
In assessing the potential health risks associated with exposure to
pesticides, attention has historically focused on single pathways of
exposure (e.g., from pesticide residues in food, water, or residential/
nonoccupational uses) for individual chemicals, and not on the
potential for individuals to be exposed to multiple pesticides by all
pathways concurrently. In 1996, FQPA modified FFDCA to require OPP to
consider potential human health risks from all pathways of dietary and
nondietary exposures to more than one pesticide acting through a common
mechanism of toxicity. This document provides guidance to OPP
scientists for evaluating and estimating the potential human risks
associated with such multichemical and multipathway exposures to
pesticides. This process is referred to as cumulative risk assessment.
The current guidance has been revised in light of review and
comment offered by the public on an earlier draft version during the
public comment period of June through September 2000 (USEPA, 2000a) (65
FR 40644, June 30, 2000 (FRL-6556-4) and 65 FR 50526, August 18, 2000
(FRL-6739-3)), by the SAP in September and December 1999, and by
comments offered by other external parties at the SAP meetings.
Furthermore, OPP has gained experience in applying the principles of
the draft guidance itself with actual datasets on pesticides that share
a common mechanism of toxicity. A pilot analysis was presented to the
SAP on 24 organophosphorus pesticides illustrating the hazard and dose-
response guidance in September 2000, and on the exposure assessment and
risk characterization process in December 2000. The SAP comments on
this pilot analysis have also led to refinements in the process of
conducting cumulative risk assessments.
Cumulative risk assessments will play a significant role in the
evaluation of risks posed by pesticides, and will enable OPP to make
regulatory decisions that more fully protect public health and
sensitive subpopulations, including infants and children. The
cumulative assessment of risks posed by exposure to multiple chemicals
by multiple pathways (including food, drinking water, and residential/
nonoccupational exposure to air, soil, grass, and indoor surfaces)
presents a formidable challenge for OPP. This guidance takes into
account the knowledge and methods available now for assessing
cumulative risk, and provides flexibility for addressing a variety of
data situations. Because methods and knowledge are expected to continue
to evolve in this area, OPP will update specific procedures with peer-
reviewed supplementary technical documentation as needed. Further
revision of the guidance itself will take place when extensive changes
are necessary.
Before undertaking a cumulative risk assessment on pesticides
sharing a common mechanism of toxicity, OPP will typically perform an
aggregate risk assessment for each chemical in the common-mechanism
group. When conducting aggregate assessments, OPP will follow the
guidance described in the document entitled ``Guidance for Performing
Aggregate Exposure and Risk Assessments'' (USEPA, 1999b), dated
November 16, 2001 (66 FR 59428, November 28, 2001) (FRL-6792-8). Using
this guidance, OPP will simultaneously consider the exposures from
food, drinking water, and residential/non-occupational uses of each
pesticide. When the aggregate risk assessments are completed for
individual chemicals that share a common mechanism of toxicity, OPP
will perform the cumulative risk assessment in the steps summarized
below.
A cumulative risk assessment begins with the identification of a
group of chemicals, a common mechanism group (CMG), that induce a
common toxic effect by a common mechanism of toxicity. OPP will follow
the framework 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,'' USEPA, 1999a (64
FR 5796, February 5, 1999) (FRL-6060-7)). Once a CMG has been
established, the next step is to evaluate registered and proposed uses
for each CMG member in order to identify potential exposure pathways
(i.e., food, drinking water, residential) and routes (i.e., oral,
inhalation, dermal). During the hazard characterization phase, the
various endpoints associated with the common mechanism of toxicity are
identified, as well as the test species/sex that might serve as a
uniform basis for determining relative potencies among the chemicals of
interest. The common effect is also evaluated to determine if it is
expressed across all exposure routes and durations of interest for each
CMG member. The temporal aspects (e.g., time to peak effects, time to
recovery) of the common mechanism toxicity are characterized to
determine the critical window of its expression.
Not all cumulative assessments need to be of the same depth and
scope. Thus, early in the cumulative assessment process, it is
important to determine the need for, or the capability to perform, a
comprehensive risk assessment. This is done by considering the number
and types of possible exposure scenarios in conjunction with the
associated residue values available. Initial toxicological and exposure
information is collected. A screening-level assessment may be conducted
that applies more conservative approaches than would a comprehensive
and refined cumulative risk assessment. For example, margins of
exposure may be based on no-observed adverse-effect-levels (NOAELs) for
the common toxic effect rather than modeling dose-response curves of
each chemical member to derive more refined relative potencies and
points of departures. For dietary food risk, treatment of 100% of crops
is assumed for each CMG chemical registered for use on a crop.
Tolerance-level residues for the exposure component of the assessment
may be assumed, rather than producing a refined estimate of actual
residue levels from monitoring. If a screening-level analysis including
such overestimates of exposure indicates that there is no risk concern,
then no further detailed assessment may be necessary. But if this
conservative approach indicates a potential for unacceptable risk, then
a refined assessment should be conducted. This may engender the need
for additional data.
As the risk assessor proceeds with the cumulative assessment, it is
important to determine candidate chemicals and uses, routes, and
pathways from the CMG that may cause cumulative effects. Cumulative
assessments should not attempt to quantify risk resulting from those
common-mechanism chemicals that will have a minimal toxic contribution
to the cumulative hazard, or from minor exposure pathways, routes, or
uses.
Exposures from minor pathways should be considered qualitatively.
Thus, a subset of common-mechanism chemicals to be included in the
quantification of cumulative risk needs to be identified from the CMG.
This subgroup is called the cumulative assessment group (CAG). The
identification of the CAG is done throughout the process as a detailed
understanding of each group member's hazard and exposure potential
emerges from the analysis. Although a
[[Page 2213]]
chemical(s) may be removed from the quantification of risk, the
rationale for such decisions will be explained. Thus, all chemicals
that were grouped by a common mechanism of toxicity will be accounted
for (qualitatively or quantitatively) in the final assessment.
OPP will use dose addition for determining the combined risk of the
CAG. This approach is consistent with the Agency's approach to
multichemical assessments that involve chemicals that are
toxicologically similar and share a common toxic effect. OPP will
depart from the dose-addition approach if there are data available to
support an alternative method. A dose-response analysis is performed on
each CAG member to determine its toxic potency for the common toxic
effect. The determination of toxic potency should, to the extent
feasible with available data, be conducted on a uniform basis (i.e.,
same measure of potency, for the same effect, from the same test
species/sex using studies of comparable methodology).
Once the toxic potency of each common-mechanism chemical is
determined, the relative potencies of the CAG members are established.
To determine relative potency, a chemical from the CAG is selected to
serve as the index chemical. The index chemical is used as the point of
reference for standardizing the common toxicity of the other chemical
members of the CAG. Once the index chemical is selected, relative
potency factors (RPFs) are calculated (i.e., the ratio of the toxic
potency of a given chemical relative to that of the index chemical).
RPFs are used to convert exposures of all chemicals in the CAG into
exposure equivalents of the index chemical. Given that the RPF method
portrays risk as exposure equivalents to one chemical (the index
compound), it is preferred that index chemical (1) have high-quality
dose-response data, (2) have a toxicological/biological profile for the
common toxicity that is representative of the common toxic effect(s),
and (3) be well characterized for the common mechanism of toxicity. The
last step in the dose-response assessment is to calculate a point of
departure(s) for the index chemical so that the risk of the CAG can be
extrapolated to anticipated human exposures.
Detailed exposure scenarios for all of the uses remaining for each
pesticide in the CAG must be developed. This includes determination of
potential human exposures by all relevant pathways, durations, and
routes that may allow simultaneous exposures, or any sequential
exposures among the CAG members that could contribute to the same joint
risk of the common toxic effect (i.e., either by overlapping internal
doses or by overlapping toxic effects). The framework for estimating
combined exposures is based on exposure to individuals, representing
differing attributes of the population (e.g., human activity patterns,
place of residence, age) that link pathways/route of exposure through
scenario building. Cumulative risk values for a given common toxic
effect are calculated separately for each exposure route and duration
and then combined. To the extent data permit, the temporal and spatial
linkages should be maintained for the many factors defining a possible
individual exposure. A decision must be made on the relative importance
of scenarios and the need for their inclusion in a quantitative
assessment, as well as on the populations of interest and locations for
evaluation in the assessment. The potential for co-occurrence of
possible exposure scenarios is evaluated. Spatial, temporal, and
demographic considerations are major factors in determining whether a
concurrent exposure is likely to occur. In other words, all exposure
events need to occur over a specific interval of time; events need to
agree in time, place, and demographic characteristics; and an
individual's dose needs to be matched with relevant toxicological
values in terms of route and duration.
Exposure input parameters must be established. The magnitude,
frequency, and duration for all pertinent exposure pathway/route
combinations are determined, and appropriate sources of use/usage
information, residues in all appropriate media, and any modifying
factors necessary for inclusion in the assessment are identified. Where
necessary, any appropriate surrogate datasets from other chemical-
specific data, published literature, or generic datasets are
identified. A trial run of a quantitative cumulative risk is conducted
by assigning route-specific and duration-specific risk metrics. The
outputs of this trial run are evaluated and a sensitivity analysis is
conducted. Subpopulations of concern are assessed.
The last step of the assessment process is to characterize the
risk. The results and conclusions of the cumulative risk analysis are
clearly described, including the relative confidence in toxicity and
exposure data sources and model inputs. The risk characterization also
includes a description of the variability. Major areas of uncertainty
are described both qualitatively and quantitatively. The magnitude and
direction of likely bias and the impact on the final assessment are
discussed. Risk contributors are identified with regard to
pesticide(s), pathway, source, time of year, and impacted subpopulation
(with particular attention to children). The basis for group
uncertainty and FQPA safety factors is explained.
In the event that a cumulative risk assessment indicates that there
may be risks of concern, OPP would need to develop risk mitigation
measures and take appropriate regulatory actions. OPP notes that the
Cumulative Risk Assessment Guidance document does not address the
process used to decide on the need for or the choice of risk mitigation
measures. It may be possible to address risk concerns through
mitigation measures that do not significantly change the use of a
pesticide (e.g. reducing application rates or changing the timing or
manner of application). In other cases, however, OPP acknowledges that
regulatory measures, that reduce or eliminate pesticide uses, may be
necessary and may result in the use of other pesticides or alternative
pest control practices, which may have their own risks and benefits.
While beyond the scope of this science policy document, OPP also
recognizes that it is important to consider potential risks and
benefits of such substitutes and alternatives to ensure that decisions
do not increase net risk, transfer risk unreasonably, and fail to
preserve important benefits wherever possible. Such consideration would
be an important part in designing mitigation options for aggregate risk
assessments for individual chemicals and for cumulative risk
assessments for chemicals sharing a common mechanism of toxicity. The
consideration of the risks and benefits of alternatives would
contribute to an understanding of whether adoption of a possible risk
mitigation measure might actually result in increased risks. When
alternative means of reducing risk exist, OPP intends that the risk
management decisions appropriately take into account which of the
mitigation measures achieves the necessary reduction in risk in the
most efficient manner, i.e., the manner that has the highest societal
benefits. Accordingly, OPP will produce an analysis of alternatives
when developing risk reduction options so that the net societal risk
and net societal benefits for the options can be estimated. This
analysis will enable risk managers to assure that there are not
significant risk transfers and uses with important benefits are
maintained, to the extent possible.
OPP is interested in understanding the views of the public on these
issues--
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both in the context of making regulatory decisions on specific
pesticides and more broadly. OPP's ongoing process of public
participation in individual pesticide tolerance reassessment decisions
affords ample opportunity for interested stakeholders to comment on
these issues as they may affect individual chemicals, classes of
chemicals, and the transfer of risks and benefits. In addition, OPP
intends to seek public input on broader methodological aspects of these
issues through its existing federal advisory committee, the Committee
to Advise on Reassessment and Transition, and/or through other avenues
that give the public an opportunity to comment. OPP intends to make
publicly available the comments received, and to use an open and
participatory process to discuss the analysis, methods, and scientific
considerations the Agency may use when characterizing changes in net
risk, and effects of any transfer of risk and benefits associated with
mitigation options.
IV. Policies Not Rules
The 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 not be
applied.
List of Subjects
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests.
Dated: January 8, 2002.
Stephen Johnson,
Assistant Administrator for Prevention, Pesticides and Toxic
Substances.
[FR Doc. 02-959 Filed 1-15-02; 8:45 am]
BILLING CODE 6580-50-S