[Federal Register Volume 65, Number 175 (Friday, September 8, 2000)]
[Notices]
[Pages 54521-54523]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-22820]
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ENVIRONMENTAL PROTECTION AGENCY
[OPP-00560A; FRL-6593-6]
Pesticides; Science Policy on Use of Data on Cholinesterase
Inhibition in Risk Assessment
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice of availability.
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SUMMARY: EPA is announcing the availability of the revised version of
the pesticide science policy document entitled ``The Use of Data on
Cholinesterase Inhibition for Risk Assessments of Organophosphorus and
Carbamate Pesticides.'' This notice is one in a series concerning
science policy documents related to implementation of the Federal Food,
Drug, and Cosmetic Act, as amended by the Food Quality Protection Act.
FOR FURTHER INFORMATION CONTACT: Dr. Penelope A. Fenner-Crisp,
Environmental Protection Agency (7501C), 1200 Pennsylvania, Ave., NW.,
Washington, DC 20460; telephone number: (703) 605-0654; fax number:
(703) 308-4776; 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:
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Examples of
Categories NAICS potentially affected
entities
------------------------------------------------------------------------
Pesticide 32532 Pesticide
Producers.......................... 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 for this document under
``Federal Register--Environmental Documents.'' You can go directly to
the Federal Register listings at http://www.epa.gov/fedrgstr/.
2. Fax-on-Demand. You may request a faxed copy of the science
policy documents, as well as supporting information, by using a
faxphone to call (202) 401-0527. Select item 6065 for the document
entitled ``Office of Pesticide Programs' Science Policy on the Use of
Data on Cholinesterase Inhibition for Risk Assessments of
Organophosphorus and Carbamate Pesticides.'' Select item 6066 for the
document entitled ``Responses to Public Comments on the Office of
Pesticide Programs' 1997 Science Policy: The Use of Data on
Cholinesterase Inhibition for Risk Assessments of Organophosphorus and
Carbamate Pesticides.'' 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-00560A which includes a
document summarizing an objection received during internal EPA review
and EPA response to the objection. 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-00557. 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
[[Page 54522]]
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 Highway, 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 About the Tolerance Reassessment
Advisory Committee
On August 3, 1996, the Food Quality Protection Act of 1996 (FQPA)
was signed into law. 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 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 some of 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 met FQPA's standard, but that could be revisited if
additional information became available or as the science evolved. In
addition, the Agency has sought 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, as directed by Vice President Albert Gore,
EPA worked with the U.S. Department of Agriculture (USDA) and a second
subcommittee of NACEPT, the Tolerance Reassessment Advisory Committee
(TRAC) to address FQPA 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 towards 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. The
CARAT held its first meeting on June 23, 2000. As a result of the TRAC
process, the Agency decided that the FQPA implementation process and
related policies would benefit from notice and comment on the major
science policy issues.
The TRAC identified nine science policy issue areas they 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),
EPA described its intended approach. Since then, EPA has been issuing a
series of draft and revised documents concerning the nine science
policies. This notice announces the availability of the revised version
of the science policy document entitled ``The Use of Data on
Cholinesterase Inhibition for Risk Assessments of Organophosphorus and
Carbamate Pesticides.''
III. Summary of Revised Science Policy Guidance Document
In 1997, EPA's Office of Pesticide Programs presented a science
policy document entitled ``The Use of Data on Cholinesterase Inhibition
for Risk Assessments of Organophosphorus and Carbamate Pesticides'' to
the FIFRA Scientific Advisory Panel for review and comment. The 1997
science policy document described the approaches OPP would employ in
assessing the potential for human health hazard from the cholinergic
effects on nervous system function following exposure to
cholinesterase-inhibiting pesticides.
In 1998, as part of its TRAC review of science policy issues, OPP
published a draft version of the 1997 TRAC science policy document
entitled ``Office of Pesticide Programs' Science Policy on the Use of
Data on Cholinesterase Inhibition for Risk Assessments of
Organophosphorus and Carbamate Pesticides'' on November 5, 1998 (63 FR
59780) (FRL-6042-3) and comments were filed under docket control number
OPP-00560. Many persons also submitted comments on the 1997 policy
document under docket control number OPP-00480 relative to the 1997 SAP
meeting (62 FR 19572, April 22, 1997) (FRL-5714-2) and under docket
control number OPP-00557 relative to the TRAC process. All of the
comments and recommendations have been reviewed by OPP and incorporated
into the revised science policy document, as appropriate.
As did the 1997 policy, this revised science policy document
emphasizes the weighing of all relevant evidence when selecting
endpoints for the hazard assessment of anticholinesterase pesticides.
This ``weight-of-the-evidence'' review, conducted on a case-by-case,
chemical-by-chemical basis, is accomplished by performing an
integrative analysis after assessing all the individual lines of
evidence (including all available data on cholinesterase inhibition in
all compartments--central nervous system, peripheral nervous system,
red blood cells, and plasma--as well as data on clinical signs,
symptoms and other physiological or behavioral effects). Weighing of
the evidence must include considerations of many factors, including the
adequacy of study protocols; quality of data; number of studies on each
endpoint; dose-dependency of responses; time course and duration of
effects; and similarities or differences of responses observed in all
the species, strains, and sexes tested for each duration and route of
exposure evaluated.
In a weight-of-the-evidence assessment of cholinesterase-inhibiting
substances, acetylcholinesterase inhibition in the nervous system is
viewed as a key event in the mechanism of toxicity of these compounds
and an important critical effect to consider in the hazard assessment.
Evaluations of the cholinergic effects (i.e., physiological and
behavioral changes and measures of cholinesterase inhibition in the
central and peripheral nervous systems) caused by exposure to the
cholinesterase-inhibiting organophosphorous and carbamate pesticides
provide direct evidence for characterizing potential human health
hazard. Because of likely differences in both the chemicals' and the
cholinesterases' pharmacodynamic properties, measures of cholinesterase
inhibition in both the central and peripheral nervous systems are
important for a thorough evaluation of
[[Page 54523]]
potential hazard. However, direct measurement of cholinesterase
activity in peripheral nervous system tissues is rarely available at
the present time. When these data are not available, as a matter of
prudent science policy protective of human health, EPA will treat
cholinesterase inhibition in the blood as a surrogate measure for the
peripheral nervous system in animals and for both the peripheral and
central nervous systems in humans. Information from blood
cholinesterase inhibition data is considered to provide important
insights into potential hazard.
Red blood cell (RBC) measures of acetylcholinesterase (AChE) are
generally preferred over plasma measures of cholinesterase activity
because data on red blood cells may provide a better representation of
the inhibition of the neural target enzyme, acetylcholinesterase. OPP,
however, may use plasma cholinesterase inhibition data under certain
circumstances, such as if red blood cell data are insufficient, of poor
quality, or unavailable; if there is a lack of dose-dependency for the
red blood cell acetylcholinesterase inhibition; or, if the dose
responses for inhibition of plasma cholinesterase more closely
approximate those for AChE inhibition in the nervous system than do the
dose responses for RBC acetylcholinesterase inhibition.
It should be noted that the present policy provides guidance only
on how to deal with data as they relate to the cholinergic endpoints
associated with nervous system function following exposure to
organophosphorous and carbamate pesticides. This scope is consistent
with all earlier descriptions of Agency assessment approaches as well
as that of other organizations with regard to the evaluation of
cholinesterase-inhibiting substances (e.g., WHO JMPR (1998), DPR-CalEPA
(1997) and other national authorities). When applying the weight-of-
the-evidence approach for selecting critical effect(s) for derivation
of a reference dose (RfD) or concentration (RfC), however, the entire
toxicological data base on a pesticide must be evaluated (i.e., there
also must be consideration of endpoints not related to the cholinergic
consequences of anticholinesterase activity, for instance, liver or
developmental toxicity or carcinogenicity). It is possible that, for
one or more of the exposure scenarios being evaluated, the non-
cholinergic effects will be identified as critical or co-critical, and
they may become a more appropriate basis for deriving RfDs or RfCs.
Finally, OPP policy documents are meant to be ``living documents,''
that is, they are open to periodic updating and revision to reflect
advances in the science. Thus, this policy, too, will be updated to
incorporate important new scientific knowledge as it becomes available.
For example, the routine availability of data on acetylcholinesterase
activity in the peripheral nervous system may allow for refinements in
the hazard assessment approach for anticholinesterase chemicals. Also,
as knowledge increases about the potential roles of the different
cholinesterases in the developing organism, particularly as they impact
the development of the nervous system, it may allow for refinements in
evaluating the potential differential sensitivity and susceptibility of
the young versus adults. In fact, a substantial research effort has
been, and continues to be, made to determine what roles acetylcholine-,
butyrylcholine-, and other esterases may play in the development of the
nervous system and in cell growth, proliferation, and death in other
tissues. OPP encourages further discussion of the possible implications
of the research findings, both for future research planning and for the
Agency's regulation of cholinesterase-inhibiting pesticides.
IV. Summary of Comments and Responses
In the public comments referred to under Unit III., some commenters
addressed the general policy and its rationale as well as all of the
specific questions posed, while other reviewers provided detailed
comments only on certain aspects of the policy. A listing of the names
and affiliations of those who submitted comments is provided at the end
of the document entitled ``Responses to Public Comments on the Office
of Pesticide Programs' 1997 Science Policy: The Use of Data on
Cholinesterase Inhibition for Risk Assessments of Organophosphorus and
Carbamate Pesticides.'' This document contains a summary of the most
significant revisions to the 1997 science policy document, followed by
responses to comments.
In the draft science policy document, the Agency requested comment
on ten questions to help focus public commment. In order to organize
the responses to these questions in the response to comments document,
the ten specific questions have been combined into six somewhat broader
topic areas:
1. General weight-of-the-evidence issues related to the use of
blood and brain measures as critical effects, differences between
plasma and RBC measures and their use, and the weight-of-the-evidence
approach (Questions 1, 2, and 9);
2. Peripheral nervous system measures (Questions 3 and 4);
3. Comparative measures in the young and adults (Questions 5 and
6);
4. Additional neurochemical measures (Questions 7 and 8);
5. Other comments.
6. Editorial comments on the science policy document (Question 10).
V. 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: August 29, 2000.
Susan H. Wayland,
Acting Assistant Administrator for Prevention, Pesticides and Toxic
Substances.
[FR Doc. 00-22820 Filed 9-7-00; 8:45 am]
BILLING CODE 6560-50-F