[Federal Register Volume 63, Number 214 (Thursday, November 5, 1998)]
[Notices]
[Pages 59780-59783]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-29665]


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ENVIRONMENTAL PROTECTION AGENCY

[OPP-00558; FRL-6042-3]


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

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice of availability.

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SUMMARY: To assure that EPA's science policies related to implementing 
the Food Quality Protection Act (FQPA) are transparent and open to 
public participation, EPA is soliciting comments on two draft science 
policy papers--``Guidance for Submission of Probabilistic Exposure 
Assessments to the Office of Pesticide Programs'' and ``Office of 
Pesticide Program's Science Policy on the Use of Cholinesterase 
Inhibition for Risk Assessments of Organophosphate and Carbamate 
Pesticides.'' These policies have been peer reviewed by the Agency's 
FIFRA Scientific Advisory Panel and are now ready for broader public 
comment.

DATES: Written comments for each science policy paper, identified by 
separate docket numbers provided in the ADDRESSES section, should be 
submitted by January 4, 1999.

ADDRESSES: The docket number for ``Guidance for Submission of 
Probabilistic Exposure Assessments to the Office of Pesticide 
Programs'' is OPP-00559 and for ``Office of Pesticide Program's Science 
Policy on the Use of Cholinesterase Inhibition for Risk Assessments of 
Organophosphate and Carbamate Pesticides'' is OPP-00560. By mail, 
submit written comments identified by the docket control number listed 
for each 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. In person, deliver comments to: Rm. 119, CM #2, 
1921 Jefferson Davis Highway, Arlington, VA.
    Comments and data may also be submitted electronically to: opp-
[email protected]. Follow the instructions under Unit V. of this document. 
No Confidential Business Information (CBI) should be submitted through 
e-mail.
    Information submitted as a comment concerning this document may be 
claimed confidential 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. A copy of the comment that 
does not contain CBI must be submitted for inclusion in the public 
record. Information not marked confidential will be included in the 
public docket by EPA without prior notice. The public docket is 
available for public inspection in Rm. 119 at the Virginia address 
given above, from 8:30 a.m. to 4 p.m., Monday through Friday, excluding 
legal holidays.

FOR FURTHER INFORMATION CONTACT: For ``Guidance for Submission of 
Probabilistic Exposure Assessments to the Office of Pesticide 
Programs'' contact by mail: Kathleen Martin, Environmental Protection 
Agency (7509C), 401 M St., SW., Washington, DC 20460. Office location, 
telephone number, and e-mail: 1921 Jefferson Davis Highway, Arlington, 
VA, 703-308-2857, fax: 703-305-5147, e-mail: [email protected].
    For ``Office of Pesticide Program's Science Policy on the Use of 
Cholinesterase Inhibition for Risk Assessments of Organophosphate and 
Carbamate Pesticides'' contact William Wooge, Environmental Protection 
Agency (7509C), 401 M St., SW., Washington, DC 20460. Office location, 
telephone number, e-mail: 1921 Jefferson Davis Highway, Arlington, VA, 
703-308-8794, fax: 703-305-5147, e-mail: [email protected].

SUPPLEMENTARY INFORMATION:

I. Electronic Availability

A. Internet

    Electronic copies of this document and the two science policy 
papers are available from the EPA Home Page at the Federal Register - 
Environmental Documents entry for this document under ``Laws and 
Regulations'' (http://www.epa.gov/fedrgstr/).

B. Fax-on-Demand

    For Fax-on-Demand, use a faxphone to call 202-401-0527 and select 
item 6021 for the draft document entitled ``Guidance for Submission of 
Probabilistic Exposure Assessments to the Office of Pesticide 
Programs'' and item 6022 for the draft document entitled ``Office of 
Pesticide Program's Science Policy on the Use of Cholinesterase 
Inhibition for Risk Assessments of Organophosphate and Carbamate 
Pesticides.''

II. Background

    On August 3, 1996, the 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 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. 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.

[[Page 59781]]

    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 five times as a full committee from May 27, 1998 through 
September 16, 1998.
    The Agency has been working with the TRAC to ensure that its 
science policies, risk assessments of individual pesticides, and 
process for decision making are transparent and open to public 
participation. An important product of these consultations with TRAC is 
the development of a framework for addressing key science policy 
issues. The Agency decided that the FQPA implementation process would 
benefit from initiating notice and comment on the major science policy 
issues.
    The 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 addition to comments received in response to these Federal 
Register notices, EPA will consider comments received during the TRAC 
meetings. Each of these issues is evolving and in a different stage of 
refinement. Accordingly, as the issues are further refined by EPA in 
consultation with USDA and others, they may also be presented to the 
SAP.
    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 is issuing a series of draft documents concerning 
nine science policy issues identified by the TRAC that are related to 
the implementation of FQPA. This notice announces the availability of 
two draft documents. The first paper relates to science policy area #2 
(Dietary exposure and Monte Carlo techniques) as described in the 
framework notice published in the Federal Register of October 29, 1998 
(63 FR 58038); this paper is one of three papers that will be issued 
for comment. The second paper addresses science policy area #9 
(Cholinesterase (ChE) Inhibition) as described in the framework notice 
published in the Federal Register of October 29, 1998 (63 FR 58038); it 
is the only paper for this area.

III. Summary of Draft Papers

A. Guidance for Submission of Probabilistic Exposure Assessments to the 
Office of Pesticide Programs

    EPA assesses pesticide dietary exposure from raw and processed 
foods using two distinct pieces of information: The amount of pesticide 
residue that is present in and on food (i.e., the residue level) and 
the types and amounts of food that we eat (i.e., food consumption). The 
residue information comes from the numerous crop field trials and other 
sources where the amount of pesticide residues on a given commodity is 
measured. Consumption information comes primarily from USDA surveys of 
what people eat. In the past, EPA has used the Dietary Risk Evaluation 
System (DRES) to combine the residue and food consumption information 
with data on a pesticide's toxicity to calculate acute and chronic 
dietary risk from food. This deterministic model calculates an average 
value (sometimes referred to as a ``point'' estimate) for these 
exposure and risk assessments.
    The science of risk assessment is constantly evolving. As better 
methods and techniques are developed, the Agency strives to incorporate 
these into its risk assessment methodologies. Over the last few years, 
a new technique has been applied to estimating acute pesticide dietary 
exposure during a single day, which is a probabilistic evaluation 
called Monte Carlo analysis. A probabilistic analysis uses the entire 
range of data from the numerous crop field trial studies or other 
sources to better estimate the distribution of exposure to the residues 
for the population of concern. This technique allows for a more 
realistic estimate of exposure, and depicts the variability in exposure 
that results from differences in individual eating patterns as well as 
differences in the levels of pesticide residues on food.
    The Agency has been developing guidance on how to conduct 
probabilistic exposure assessments for pesticides as well as guidance 
to Agency reviewers on how to evaluate such assessments. In March 1998, 
draft guidance was presented to the SAP. The SAP was very supportive of 
the proposed guidance document and in general agreed with the proposed 
approach. EPA has since revised the draft guidance, incorporating the 
SAP's advice. Today, this revised draft guidance is being made 
available for public comment. EPA is inviting public comment on several 
issues listed in Unit IV.A.
    The draft guidance is related to two of the other nine TRAC science 
policy issues as follows:
    1. Dietary exposure estimates (science policy issue area #4). 
Dietary exposure estimates derived from probabilistic assessments are 
one input in the overall assessment of dietary exposures.
    2. Aggregate exposure (science policy issue area #7). Again, 
exposure estimates derived from probabilistic assessments are part of 
the aggregate exposures. Also, the use of probabilistic techniques is 
being discussed among the scientific community as a method for 
aggregating exposure from multiple sources and pathways.
    The draft guidance is not intended to address the following two 
other related issues:
    1. The procedures (statistical and otherwise) used to address 
situations where no residue is detected.
    2. The rationale for the Agency's interim decision to regulate at 
the 99.9th percentile of exposure when using probabilistic exposure 
evaluation techniques.
    Separate issue papers will be prepared according to the schedule in 
the framework Federal Register notice to deal with these two topics.
    A number of comments were provided by various industry and public 
interest groups in response to the TRAC meetings, which began in May 
1998. Commenters included the Natural Resources Defense Council (NRDC), 
the National Food Processors Association (NFPA), Latham and Watkins, 
and the Implementation Working Group (IWG). However, only IWG's 
comments related to the draft guidance announced (in revised form) in 
this Federal Register notice. The IWG, a coalition of farm, food, 
pesticide manufacturing, and pest management organizations, provided a 
``road map'' report entitled ``A Science-Based Workable Framework for 
Implementing the Food Quality Protection Act.'' The IWG report stated 
that the Agency should more fully utilize probabilistic techniques for 
dietary, non-dietary and aggregate exposure assessments and that EPA 
regulatory staff should become more familiar with the concepts of using 
probabilistic analysis in decision making.

[[Page 59782]]

B. Office of Pesticide Program's Science Policy on the Use of 
Cholinesterase Inhibition for Risk Assessments of Organophosphate and 
Carbamate Pesticides

    Most organophosphate (OP) and certain carbamate insecticides exert 
their toxic effects on insects and mammals by the mechanism of ChE 
inhibition. Communication between a large number of nerve cells in the 
peripheral and central nervous system is by means of acetylcholine, a 
neuro-transmitter. Acetylcholinesterase is the enzyme that breaks down 
acetylcholine after it has communicated the nerve signal between two 
nerve cells or nerve and muscle cells. Inhibition of this enzyme 
prolongs the action of acetylcholine and results in the acute toxic 
effects known for these chemicals such as nausea, dizziness, confusion 
and, at high concentrations, more serious effects such as respiratory 
paralysis and death. This can also result in chronic effects that have 
been observed with many of these insecticides. Measures of 
cholinesterase levels in the blood or nervous system after exposure to 
OPs and certain carbamates have become the most common endpoint used in 
risk assessments of these chemical classes. For at least the last 10 
years, EPA has used plasma, red blood cells, and/or brain ChE 
inhibition as the basis for determining critical effect levels and 
setting reference doses.
    Over the last several years, the Agency has engaged with outside 
scientists and the regulatory community about which measures of ChE 
inhibition may be used for setting reference doses in risk assessments. 
Much of the discussion focused on two issues:
    1. The role of blood measures, since blood cholinesterases are not 
part of the nervous system and therefore are only an indirect measure 
of neurotoxicity.
    2. Whether plasma cholinesterases should be treated differently 
from red blood cell cholinesterases.
    In June 1997, the Agency made a presentation to the SAP including a 
literature review, a series of case studies, a summary of activities 
related to methodology of ChE measurement, and a briefing. This 
briefing paper presented to the SAP, ``Office of Pesticide Programs 
Science Policy on the Use of Cholinesterase Inhibition for Risk 
Assessment of Organophosphate and Carbamate Pesticides'' (draft, April 
30, 1997), provided EPA's analysis of the issues and options and its 
proposed policy to use a weight of evidence approach that would 
consider all of the data that might result in the use of ChE measures 
in plasma, red blood cells, and/or the brain for defining critical 
effects. In addition, EPA also asked the SAP about the feasibility of 
using measures of peripheral nervous system tissue to replace blood 
measures, which largely serve as indirect estimators of ChE inhibition 
in the peripheral nervous system in animals. The report of the SAP 
addresses these issues and is also included in the docket. The Agency's 
briefing paper cited above has been updated and is being made available 
for comment with this notice.
    The IWG prepared a paper evaluating several science policy issues 
relating to EPA's implementation of FQPA. Issue paper II of the IWG 
report discussed the choice and use of endpoints in risk assessments of 
ChE inhibitors and provided a number of comments about their use. The 
IWG asserted several opinions: that ChE inhibition in blood itself is 
not an adverse effect; that use of ChE inhibition in blood has the 
effect of adding a safety factor; and that the additional safety factor 
should be considered when applying other safety factors related to 
infants and children.
    During the public comment period for the SAP review, the Acute 
Cholinesterase Risk Assessment Work Group, a group of pesticide 
manufacturing organizations, proposed a complex alternative policy for 
using measures of ChE inhibition in risk assessments. They proposed not 
using plasma measures, reducing the uncertainty factor for red blood 
cell measures, establishing a generic threshold of 20 percent 
difference for blood or brain measures, and provided other comments.
    The Natural Resources Defense Council, an environmental group, in a 
brief oral presentation to the SAP, provided general support for the 
Agency's proposed policy, but emphasized the need for broader pre-natal 
and post-natal testing of pesticides to provide more data specific to 
fetuses, infants, and children. This would, in their view, include both 
cholinesterase data and data on a variety of neurological functions, 
including in particular learning and memory.
    Other regulatory bodies (i.e., agencies from California and Canada) 
and public commenters from outside the United States (including 
scientists from Great Britain and individual physicians who have worked 
with the World Health Organization) described their own policies and 
how those policies generally placed less reliance on plasma measures of 
ChE inhibition as a risk assessment endpoint.

IV. Questions/Issues for Comment

A. Guidance for Submission of Probabilistic Exposure Assessments to the 
Office of Pesticide Programs

    1. Should outlier data points in residue or consumption data sets 
be excluded from consideration? If so, then what should be the criteria 
for excluding a data point from either food consumption or residue data 
sets on the grounds that it is an outlier?
    2. What criteria should be used to determine if a data set is 
sufficiently ``representative'' of the population of interest to be 
used in a probablistic assessment? Are there minimum size or Quality 
Assurance/Quality Control (QA/QC) requirements that should be met?
    3. Should the Agency allow exposure assessments to include data 
reflecting the range of typical application parameters? Are the 
conditions for accepting residue data based on typical parameters 
appropriate, or should they be modified?
    4. Do the currently available consumption data permit probabilistic 
assessment of chronic dietary risk? If not, is there an appropriate 
process for using the available consumption data to permit 
probabilistic assessment of chronic dietary risk?
    5. Is there a process or procedure which would allow the Agency to 
utilize post-farm monitoring data on composite samples (e.g., from the 
Food and Drug Administration (FDA), USDA, and State pesticide 
monitoring data) to assess acute dietary exposure for unblended 
commodities?
    6. Is it appropriate to assess acute dietary risk on a population 
basis, and to assess short- and intermediate-term occupational and 
residential exposure on an exposed-individual basis? If it is more 
appropriate to assess short- and intermediate-term occupational and 
residential risk on a population basis, is there a process to do so?
    7. What changes or additions to the document would improve its 
readability and make it easier for general audiences to understand? For 
example, would it be helpful to include a glossary of terms? Are there 
key scientific concepts that need to be better explained for a lay 
audience? Would the addition of a case study make any of the concepts 
easier to understand?

B. Office of Pesticide Program's Science Policy on the Use of 
Cholinesterase Inhibition for Risk Assessments of Organophosphate and 
Carbamate Pesticides

    1. How should EPA use measures of ChE inhibition in plasma, red 
blood cells, and brain in determination of

[[Page 59783]]

critical effect levels and setting reference doses?
    2. Should plasma and red blood cell measures of ChE inhibition be 
treated differently from brain measures of ChE inhibition and/or from 
one another?
    3. How should measures of peripheral tissues be used in these 
processes of risk assessment, both in a practical sense and a science 
policy sense?
    4. Can measures of ChE inhibition in peripheral tissues, such as 
the heart and salivary glands, be used as a supplement or even an 
alternative to blood measures?
    5. Should comparative data on ChE inhibition in the young exposed 
pre-natally, during infancy (nursing), and during childhood be 
considered essential for defining the relative sensitivity of the young 
and adults?
    6. Are other measures, such as functional measures of clinical 
signs, or learning and memory, similarly important?
    Based on special additional recommendations of the SAP, EPA wishes 
to highlight two other issues for public comment.
    The first is the SAP's recommendation that plasma cholinesterase be 
differentiated by use of selective inhibitors into acetylcholinesterase 
and butyrylcholinesterase. At present, most animal studies received by 
EPA do not differentiate between these enzymes. An important part of 
the argument made for consideration of plasma activity was the fact 
that for rat studies, nearly half of the plasma cholinesterase is 
acetylcholinesterase, identical to the neuronal form. Such differential 
analyses would provide additional data on this topic.
    7. Should EPA require the differentiation of acetylcholinesterase 
and butyrylcholinesterase in plasma, and how might this data be used?
    The second is the SAP's recommendation that EPA ask for receptor 
binding assays for long term studies. A common consequence of prolonged 
ChE inhibition in the nervous system is the down regulation of 
cholinergic receptors. This represents a longer term response to 
exposure than the inhibition of enzyme activity. This effect might be 
differentially affected by some chemicals, and its time course might 
differ from enzyme activity. Such data would help to broaden the data 
base on which to characterize the hazards of these chemicals.
    8. Should EPA require receptor binding assays for long term 
(subchronic and chronic) studies, and how should such data be 
interpreted?
    9. A number of parameters related to the neurotoxicological 
potential of cholinesterase-inhibiting pesticides are measured and 
considered when developing a hazard characterization for these 
chemicals. Some of these parameters (e.g., clinical signs) represent 
direct observations of this potential; others serve as surrogates 
(e.g., inhibition of red cell cholinesterase) for potential effects not 
currently measured or observed directly. OPP has proposed to use a 
weight-of-the-evidence approach when characterizing the hazard of these 
chemicals and developing health-based benchmarks such as reference 
doses. A weight-of-the-evidence approach obligates the risk assessor to 
consider all of the study results as a whole, rather than focusing on 
any single result in isolation of the others. Is this approach a 
reasonable means for evaluating the overall significance of the 
potential neurotoxic effects associated with this type of pesticide?
    10. What changes or additions to the document would improve its 
readability and make it easier for general audiences to understand? For 
example, would it be helpful to expand the glossary of terms? Are there 
key scientific concepts that need to be better explained for a lay 
audience? Would the addition of more examples make the concepts easier 
to understand?

V. Public Record and Electronic Submissions

    A record has been established for these policy guidances under 
docket control numbers OPP-00559 and OPP-00560 (including comments and 
data submitted electronically as described below). A public version of 
this record, including printed, paper versions of electronic comments, 
which does not include any information claimed as CBI, is available for 
inspection from 8:30 a.m. to 4 p.m., Monday through Friday, excluding 
legal holidays. The official record is located at the Virginia address 
in ``ADDRESSES'' at the beginning of this document.
    Electronic comments can be sent directly to EPA at:
    [email protected]


    Electronic comments must be submitted as an ASCII file avoiding the 
use of special characters and any form of encryption. Comment and data 
will also be accepted on 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 numbers OPP-00559 and OPP-00560. Electronic comments 
on this notice may be filed online at many Federal Depository 
Libraries.

VI. Contents of Docket

    Documents that are referenced in this notice document will be 
inserted in the docket under the document control numbers OPP-00559 and 
OPP-00560. In addition, documents referenced in in the framework 
notice, which published in the Federal Register on October 29, 1998 (63 
FR 58038) will also be 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: October 30, 1998.
Lynn R. Goldman,
Assistant Administrator for Prevention, Pesticides and Toxic 
Substances.
[FR Doc. 98-29665 Filed 11-4-98; 8:45 am]
BILLING CODE 6560-50-F