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Esfenvalerate - Pesticide Petition Filing 3/01

ENVIRONMENTAL PROTECTION AGENCY
[PF-1011; FRL-6774-5]
Notice of Filing a Pesticide Petition to Establish a Tolerance
for a Certain Pesticide Chemical in or on Food
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice.
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SUMMARY: This notice announces the initial filing of a pesticide
petition proposing the establishment of regulations for residues of a
certain pesticide chemical in or on various food commodities.

DATES: Comments, identified by docket control number PF-1011, must be
received on or before April 27, 2001.

ADDRESSES: Comments may be submitted by mail, electronically, or in
person. Please follow the detailed instructions for each method as
provided in Unit I.C. of the SUPPLEMENTARY INFORMATION. To ensure
proper receipt by EPA, it is imperative that you identify docket
control number PF-1011 in the subject line on the first page of your
response.

FOR FURTHER INFORMATION CONTACT: By mail: Leonard Cole, Registration
Division (7505C), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460;
telephone number: (703) 305-5412; e-mail address: cole.leonard@epa.gov.

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

    You may be affected by this action if you are an agricultural
producer, food manufacturer or pesticide manufacturer. Potentially
affected categories and entities may include, but are not limited to:

------------------------------------------------------------------------
                                                          Examples of
           Categories                 NAICS codes         potentially
                                                      affected  entities
------------------------------------------------------------------------
Industry                          111                 Crop production
                                  112                 Animal production
                                  311                 Food manufacturing
                                  32532               Pesticide
                                                       manufacturing
------------------------------------------------------------------------

    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 in the table could also be
affected. The North American Industrial Classification System (NAICS)
codes have been provided to assist you and others in determining
whether or not this action might apply to certain entities. If you have
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 and Other Related Documents?

    1. Electronically. You may obtain electronic copies of this
document, and certain other related documents that might be available
electronically, from the EPA Internet Home Page at http://www.epa.gov/.
To access this document, on the Home Page select "Laws and
Regulations" and then look up the entry for this document under the
"Federal Register--Environmental Documents." You can also 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 PF-1011. The official record
consists of the documents specifically referenced in this action, any
public comments received during an applicable comment period, 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 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.

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 PF-1011 in the subject line on the
first page of your response.
    1. By mail. Submit your comments to: Public Information and Records
Integrity Branch (PIRIB), Information Resources and Services Division
(7502C), Office of Pesticide Programs (OPP), Environmental Protection
Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460.
    2. In person or by courier. Deliver your comments to: Public
Information and Records Integrity Branch (PIRIB), Information Resources
and Services Division (7502C), Office of Pesticide Programs (OPP),
Environmental Protection Agency, Rm. 119, Crystal Mall #2, 1921
Jefferson Davis Highway, Arlington, VA. The PIRIB is open from 8:30
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The
PIRIB telephone number is (703) 305-5805.
    3. Electronically. You may submit your comments electronically by
e-mail to: opp-docket@epa.gov, or you can submit a computer disk as
described above. Do not submit any information electronically that you
consider to be CBI. Avoid the use of special characters and any form of
encryption. Electronic submissions will be accepted in Wordperfect 6.1/
8.0 or ASCII file format. All comments in electronic form must be
identified by docket control number PF-1011. Electronic comments may
also be filed online at many Federal Depository Libraries.

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

    Do not submit any information electronically that you consider to
be CBI. You may claim information that you submit to EPA in response to
this document as CBI by marking any part or all of that information as
CBI. Information so marked will not be disclosed except in accordance
with procedures set forth in 40 CFR part 2. In addition to one complete
version of the comment that includes any information claimed as CBI, a
copy of the comment that does not contain the information claimed as
CBI must be submitted for inclusion in the public version of the
official record. Information not marked confidential will be included
in the public version of the official record without prior notice. If
you have any questions about CBI or the procedures for claiming CBI,
please consult the person identified under FOR FURTHER INFORMATION
CONTACT.

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

    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 copies of any technical information and/or data you used
that support your views.
    4. If you estimate potential burden or costs, explain how you
arrived at the estimate that you provide.
    5. Provide specific examples to illustrate your concerns.
    6. Make sure to submit your comments by the deadline in this
notice.
    7. To ensure proper receipt by EPA, be sure to identify the docket
control number assigned to this action in the subject line on the first
page of your response. You may also provide the name, date, and Federal
Register citation.

II. What Action is the Agency Taking?

    EPA has received a pesticide petition as follows proposing the
establishment and/or amendment of regulations for residues of a certain
pesticide chemical in or on various food commodities under section 408
of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a.
EPA has determined that this petition contains data or information
regarding the elements set forth in section 408(d)(2); however, EPA has
not fully evaluated the sufficiency of the submitted data at this time
or whether the data support granting of the petition. Additional data
may be needed before EPA rules on the petition.

List of Subjects

    Environmental protection, Agricultural commodities, Feed additives,
Food additives, Pesticides and pests, Reporting and recordkeeping
requirements.

    Dated: March 19, 2001.
  James Jones,
Director, Registration Division, Office of Pesticide Programs.

Summary of Petition

    The petitioner summary of the pesticide petition is printed below
as required by section 408(d)(3) of the FFDCA. The summary of the
petition was prepared by the petitioner and represents the view of the
petitioner. EPA is publishing the petition summary verbatim without
editing it in any way. The petition summary announces the availability
of a description of the analytical methods available to EPA for the
detection and measurement of the pesticide chemical residues or an
explanation of why no such method is needed.

McLaughlin Gormley King Company

PP 0F6168

    EPA has received a pesticide petition (PP 0F6168) from McLaughlin
Gormley King Company, 8810 Tenth Avenue North, Minneapolis, MN 55427
proposing pursuant to section 408(d) of the FFDCA, 21 U.S.C. 346a(d),
to amend 40 CFR part 180 by establishing a tolerance for residues of
esfenvalerate in or on the raw agricultural commodities unshelled
peanut kernels, 0.20 parts per million (ppm); unshelled cocoa beans,
1.00 ppm; shelled almonds, 50 ppm; and shelled walnuts, 15 ppm. EPA has
determined that the petition contains data or information regarding the
elements set forth in section 408(d)(2) of the FFDCA; however, EPA has
not fully evaluated the sufficiency of the submitted data at this time
or whether the data support granting of the petition. Additional data
may be needed before EPA rules on the petition.

A. Residue Chemistry

    1. Plant and animal metabolism. The metabolism and chemical nature
of residues of fenvalerate in plants and animals is adequately
understood. The fate of fenvalerate has been extensively studied using
radioactive tracers in plant and animal metabolism/nature of the
residue studies previously submitted to the Agency. These studies have
demonstrated that the parent compound is the only residue of
toxicological significance. EPA has concluded that the qualitative
nature of the residue is the same for both fenvalerate and
esfenvalerate.
    2. Analytical method. There is a practical analytical method
utilizing electron-capture gas chromatography (GC) with nitrogen
phosphorous detection available for enforcement with a limit of
detection (LOD) that allows monitoring food with residues at or above
tolerance levels. The LOD for this updated method is the same as that
of the current pesticide analytical manual (PAM) II, which is 0.01 ppm.
    3. Magnitude of residues. Fenvalerate is a racemic mixture of four
isomers (S,S; R,S; S,R; and R,R). Technical Asana®
(esfenvalerate) is enriched in the insecticidally active S,S-isomer
(84%). Tolerance expressions are proposed for esfenvalerate based on
the sum of all isomers. The following tolerances are proposed:
unshelled peanut kernels, 0.20 ppm; unshelled cocoa beans, 1.00 ppm;
shelled almonds, 50 ppm; and shelled walnuts, 15 ppm; resulting from
post-harvest treatment. Magnitude of residue studies support the
proposed tolerance.

B. Toxicological Profile

    1. Acute toxicity. A battery of acute toxicity studies places
technical esfenvalerate in toxicity category II for acute oral toxicity
(rat LD50 87.2 milligrams/kilograms (mg/kg)), category III
for acute dermal (rabbit LD50 >2,000 mg/kg) and primary eye
irritation (mild irritation in rabbits), and category IV for primary
skin irritation (minimal skin irritation in rabbits that reversed
within 72 hours after treatment). Acute inhalation on technical grade
active ingredient was waived due to negligible vapor pressure. A dermal
sensitization test on esfenvalerate in guinea pigs showed no
sensitization.
    2. Genotoxicty. Esfenvalerate did not induce micronuclei in bone
marrow of
mice given up to 150 mg/kg intraperitoneally. Esfenvalerate did not
induce unscheduled DNA synthesis (UDS) in HeLa cells. Other genetic
toxicology studies submitted on racemic fenvalerate indicate that the
mixture containing equal parts of the four stereoisomers is not
mutagenic in bacteria. The racemic mixture was also negative in a mouse
host mediated assay and in a mouse dominant lethal assay.
    3. Reproductive and developmental toxicity. Esfenvalerate was
administered to pregnant female rats by gavage in a pilot developmental
study at doses of 0, 1, 2, 3, 4, 5, and 20 mg/kg/day and a main study
at 0, 2.5, 5, 10, and 20 mg/kg/day. Maternal clinical signs (abnormal
gait and mobility) were observed at 2.5 mg/kg/day and above. A maternal
no observed adverse effect level (NOAEL) of 2 mg/kg/day was established
on the pilot study. The developmental NOAEL was >20 mg/kg/day.
    Esfenvalerate was administered by gavage to pregnant female rabbits
in a pilot developmental study at doses of 0, 2, 3, 4, 4.5, 5, and 20
mg/kg/day and a main study at doses of 0, 3, 10, and 20 mg/kg/day.
Maternal clinical signs (excessive grooming) were observed at 3 mg/kg/
day and above. A maternal NOAEL of 2 mg/kg/day was established on the
pilot study. The developmental NOAEL was >20 mg/kg/day.
    A 2-generation feeding study with esfenvalerate was conducted in
the rat at dietary levels of 0, 75, 100, and 300 ppm. Skin lesions and
minimal (non biologically significant) parental body weight effects
occurred at 75 ppm. The NOAEL for reproductive toxicity was 75 ppm
(4.2-7.5 mg/kg/day) based on decreased pup weights at 100 ppm.
    4. Subchronic toxicity. Two 90-day feeding studies with
esfenvalerate were conducted in rats--one at 50, 150, 300, and 500 ppm
esfenvalerate, and a second at 0, 75, 100, 125, and 300 ppm to provide
additional dose levels. The NOAEL was 125 ppm (6.3 mg/kg/day) based on
clinical signs (jerky leg movements) observed at 150 ppm (7.5 mg/kg/
day) and above. A three-month subchronic study in dogs was satisfied by
1 year oral study in dogs, in which the NOAEL was 200 ppm (5 mg/kg/
day).
    5. Chronic toxicity. The NOAEL was 200 ppm (5 mg/kg/day). An effect
level for dietary administration of esfenvalerate to dogs of 300 ppm
had been established earlier in a 3-week pilot study used to select
dose levels for the chronic dog study.
    One chronic study with esfenvalerate and three chronic studies with
fenvalerate have been conducted in mice.
    In an 18-month study, mice were fed 0, 35, 150, or 350 ppm
esfenvalerate. Mice fed 350 ppm were sacrificed within the first 2
months of the study after excessive self-trauma related to skin
stimulation and data collected were not used in the evaluation of the
oncogenic potential of esfenvalerate. The NOAEL was 35 ppm (4.29 and
5.75 mg/kg/day for males and females, respectively) based on lower body
weight and body weight gain at 150 ppm. Esfenvalerate did not produce
carcinogenicity.
    In a 2-year feeding study, mice were administered 0, 10, 50, 250,
or 1,250 ppm fenvalerate in the diet. The NOAEL was 10 ppm (1.5 mg/kg/
day) based on granulomatous changes (related to fenvalerate only, not
esfenvalerate) at 50 ppm (7.5 mg/kg/day). Fenvalerate did not produce
carcinogenicity.
    In an 18-month feeding study, mice were fed 0, 100, 300, 1,000, or
3,000 ppm fenvalerate in the diet. The NOAEL is 100 ppm (15.0 mg/kg/
day) based on fenvalerate-related microgranulomatous changes at 300 ppm
(45 mg/kg/day). No compound-related oncogenicity occurred.
    Mice were fed 0, 10, 30, 100, or 300 ppm fenvalerate for 20 months.
The NOAEL was 30 ppm (3.5 mg/kg/day) based on red blood cell effects
and granulomatous changes at 100 ppm (15 mg/kg/day). Fenvalerate was
not carcinogenic at any concentration.
    In a 2-year study, rats were fed 1, 5, 25, or 250 ppm fenvalerate.
A 1,000 ppm group was added in a supplemental study to establish an
effect level. The NOAEL was 250 ppm (12.5 mg/kg/day). At 1,000 ppm (50
mg/kg/day), hind limb weakness, lower body weight, and higher organ-to-
body weight ratios were observed. Fenvalerate was not carcinogenic at
any concentration. (A conclusion that fenvalerate is associated with
the production of spindle cell sarcomas at 1,000 ppm was retracted by
EPA).
    EPA has classified esfenvalerate in Group E--evidence of
noncarcinogenicity for humans.
    The NOAEL was 200 ppm (5 mg/kg/day). An effect level for dietary
administration of esfenvalerate to dogs of 300 ppm had been established
earlier in a 3-week pilot study used to select dose levels for the
chronic dog study.
    One chronic study with esfenvalerate and three chronic studies with
fenvalerate have been conducted in mice.
    In an 18-month study, mice were fed 0, 35, 150, or 350 ppm
esfenvalerate. Mice fed 350 ppm were sacrificed within the first 2
months of the study after excessive self-trauma related to skin
stimulation and data collected were not used in the evaluation of the
oncogenic potential of esfenvalerate. The NOAEL was 35 ppm (4.29 and
5.75 mg/kg/day for males and females, respectively) based on lower body
weight (bwt) and body weight gain at 150 ppm. Esfenvalerate did not
produce carcinogenicity.
    In a 2-year feeding study, mice were administered 0, 10, 50, 250,
or 1,250 ppm fenvalerate in the diet. The NOAEL was 10 ppm (1.5 mg/kg/
day) based on granulomatous changes (related to fenvalerate only, not
esfenvalerate) at 50 ppm (7.5 mg/kg/day). Fenvalerate did not produce
carcinogenicity.
    In an 18-month feeding study, mice were fed 0, 100, 300, 1,000, or
3,000 ppm fenvalerate in the diet. The NOAEL is 100 ppm (15.0 mg/kg/
day) based on fenvalerate-related microgranulomatous changes at 300 ppm
(45 mg/kg/day). No compound-related oncogenicity occurred. Mice were
fed 0, 10, 30, 100, or 300 ppm fenvalerate for 20 months. The NOAEL was
30 ppm (3.5 mg/kg/day) based on red blood cell effects and
granulomatous changes at 100 ppm (15 mg/kg/day). Fenvalerate was not
carcinogenic at any concentration.
    In a 2-year study, rats were fed 1, 5, 25, or 250 ppm fenvalerate.
A 1,000 ppm group was added in a supplemental study to establish an
effect level. The NOAEL was 250 ppm (12.5 mg/kg/day). At 1,000 ppm (50
mg/kg/day), hind limb weakness, lower body weight, and higher organ-to-
body weight ratios were observed. Fenvalerate was not carcinogenic at
any concentration. (A conclusion that fenvalerate is associated with
the production of spindle cell sarcomas at 1,000 ppm was retracted by
EPA). EPA has classified esfenvalerate in Group E--evidence of
noncarcinogenicity for humans.
    6. Animal metabolism. After oral dosing with fenvalerate, the
majority of the administered radioactivity was eliminated in the
initial 24 hours. The metabolic pathway involved cleavage of the ester
linkage followed by hydroxylation, oxidation, and conjugation of the
acid and alcohol moieties.
    7. Metabolite toxicology. The parent molecule is the only moiety of
toxicological significance appropriate for regulation in plant and
animal commodities.
    8. Endocrine disruption. Estrogenic effects have not been observed
in any studies conducted on fenvalerate or esfenvalerate. In subchronic
or chronic studies there were no lesions in reproductive systems of
males or females. In the recent reproduction
study with esfenvalerate, full histopathological examination of the
pituitary and the reproductive systems of males and females was
conducted. There were no compound-related gross or histopathological
effects. There were also no compound-related changes in any measures of
reproductive performance including mating, fertility, or gestation
indices or gestation length in either generation. There have been no
effects on offspring in developmental toxicity studies. EPA is required
to develop an endocrine disrupter screening program. EPA will decide
whether further testing of esfenvalerate is required when this program
is in place.

C. Aggregate Exposure

    1. Dietary exposure. Tolerances have been established for the
residues of fenvalerate/esfenvalerate, in or on a variety of
agricultural commodities. In addition, pending tolerance petitions
exist for use of esfenvalerate on sugar beets, sorghum, head lettuce,
celery, pistachios, and a number of other minor use commodities. For
purposes of assessing dietary exposure, chronic and acute dietary
assessments have been conducted using all existing and pending
tolerances for esfenvalerate. EPA reviewed (August 2, 1997) the
existing toxicology data base for esfenvalerate and selected the
following toxicological endpoints. For acute toxicity, EPA established
a NOAEL of 2.0 mg/kg/day from rat and rabbit developmental studies
based on maternal clinical signs at higher concentrations. A margin of
exposure (MOE) of 100 was required. For chronic toxicity EPA
established the reference dose (RfD) for esfenvalerate at 0.02 mg/kg/
day. This RfD was also based on a NOAEL of 2.0 mg/kg/day in the rat
developmental study with an uncertainty factor (UF) of 100.
Esfenvalerate is classified as a Group E. There is no evidence of
carcinogenicity in either rats or mice.
    2. Food. A chronic dietary exposure assessment was conducted using
Novigen's dietary exposure estimate model (DEEM). Anticipated residues
and adjustment for percent crop treated were used in the chronic
dietary risk assessment. The percentages of the RfD utilized by the
most sensitive sub-population, children 1 to 6 years, was 4.6% based on
a daily dietary exposure of 0.000911 mg/kg/day. Chronic exposure for
the overall U.S. population was 1.9% of the RfD based on a dietary
exposure of 0.000376 mg/kg/day. This assessment has been approved by
EPA and included pending tolerances (including lettuce) and all food
tolerances for incidental residues from use in food handling
establishments. EPA has no concern for exposures below 100% of the RfD
because the RfD represents the level at or below which daily aggregate
dietary exposure over a lifetime will not pose appreciable risks to
human health. Esfenvalerate is classified as a Group E carcinogen- -no
evidence of carcinogenicity in rats or mice. Therefore, a
carcinogenicity risk analysis is not required.
    Potential acute exposures from food commodities were estimated
using a Tier 3 (Monte Carlo) analysis and appropriate processing
factors for processed food and distribution analysis. This analysis
used field trial data to estimate exposure and Federal and market
survey information to derive the percent of crop treated. EPA
considered these data reliable and used the upper end estimate of
percent crop treated in order to not underestimate any significant
subpopulation. Regional consumption information was taken into account.
The MOEs for the most sensitive sub-population (children 1 to 6 years)
were 202 and 103 at the 99th and 99.9th
percentile of exposure, respectively, based on daily exposures of
0.009908 and 0.019445 mg/kg/day. The MOEs for the general population
are 355 and 171 at the 99th and 99.9th percentile
of exposure, respectively, based on daily exposure estimates of
0.005635 and 0.011717 mg/kg/day. EPA has stated there is no cause for
concern if total acute exposure calculated for the 99.9th
percentile yields a MOE of 100 or larger. This acute dietary exposure
estimate is considered conservative and EPA considered the MOEs
adequate in a final rule (62 FR 63019, November 26, 1997).
    3. Drinking water. Esfenvalerate is immobile in soil and will not
leach into ground water. Due to the insolubility and lipophilic nature
of esfenvalerate, any residues in surface water will rapidly and
tightly bind to soil particles and remain with sediment, therefore not
contributing to potential dietary exposure from drinking water.
    A screening evaluation of leaching potential of a typical
pyrethroid was conducted using EPA's pesticide root zone model (PRZM).
Based on this screening assessment, the potential concentrations of a
pyrethroid in ground water at depths of 1 and 2 meters are essentially
zero (much less than 0.001 parts per billion (ppb)).
    Surface water concentrations for pyrethroids were estimated using
PRZM\3\ and exposure analysis modeling system (EXAMS) using standard
EPA cotton runoff and Mississippi pond scenarios. The maximum
concentration predicted in the simulated pond was 0.052 ppb.
Concentrations in actual drinking water would be much lower than the
levels predicted in the hypothetical, small, stagnant farm pond model
since drinking water derived from surface water would be treated before
consumption. Chronic drinking water exposure was estimated to be
0.000001 mg/kg/day for both the U.S. general population and for non-
nursing infants. Less than 0.1% of the RfD was occupied by both
population groups.
    Using these values, the contribution of water to the acute dietary
risk estimate was estimated for the U.S. population to be 0.000019 mg/
kg/day at the 99th percentile and 0.000039 mg/kg/day at the
99.9th percentile resulting in MOEs of 105,874 and 51,757,
respectively. For the most sensitive subpopulation, non-nursing infants
less than 1 year old, the exposure is 0.000050 mg/kg/day and 0.000074
mg/kg/day at the 99th and 99.9th percentile,
respectively, resulting in MOEs of 39,652, and 27,042, respectively.
Therefore there is reasonable certainty of no harm from exposure to
esfenvalerate from drinking water.
    4. Non-dietary exposure. Esfenvalerate is registered for non-crop
uses including spray treatments in and around commercial and
residential areas, treatments for control of ectoparasites on pets,
home care products including foggers, pressurized sprays, crack and
crevice treatments, lawn and garden sprays, and pet and pet bedding
sprays. For the non-agricultural products, the very low amounts of
active ingredient they contain, combined with the low vapor pressure
(1.5 x 10**-9 mm mercury at 25 \o\C) and low dermal
penetration, would result in minimal inhalation and dermal exposure.
    To assess risks from (nonfood) short-term and intermediate-term
exposure, EPA has recently selected a toxicological endpoint of 2.0 mg/
kg/day, the NOAEL from the rat and rabbit developmental studies. For
dermal penetration/absorption, EPA selected 25% dermal absorption based
on the weight-of-evidence available for structurally-related
pyrethroids. For inhalation exposure, EPA used the oral NOAEL of 2.0
mg/kg/day and assumed 100% absorption by inhalation. Individual non-
dietary risk exposure analyses were conducted using a flea infestation
scenario that included pet spray, carpet, and room treatment, and lawn
care, respectively. The total potential short-term and intermediate-
term aggregate non-dietary exposure including lawn, carpet, and pet
uses are: 0.000023 mg/kg/day for adults, 0.00129
mg/kg/day for children 1 to 6 years, and 0.00138 mg/kg/day for infants
less than one year old.
    EPA concluded that the potential non-dietary exposure for
esfenvalerate are associated with substantial margins of safety (62 FR
63019).
    5. Aggregate exposure--dietary and non dietary exposure. EPA has
concluded that aggregate chronic exposure to esfenvalerate from food
and drinking water will utilize 2.0% of the RfD for the U.S. population
based on a dietary exposure of 0.000378 mg/kg/day. The major
identifiable subgroup with the highest aggregate exposure are children
1 to 6 years old. EPA generally has no concern for exposures below 100%
of the RfD because the RfD represents the level at or below which daily
aggregate dietary exposure over a lifetime will not pose appreciable
risks to human health.
    The acute aggregate risk assessment takes into account exposure
from food and drinking water. The potential acute exposure from food
and drinking water to the overall U.S. population provides an acute
dietary exposure of 0.011756 mg/kg/day with an MOE of 170. This acute
dietary exposure estimate is considered conservative, using anticipated
residue values and percent crop treated data in conjunction with Monte
Carlo analysis.
    Short-term and intermediate-term aggregate exposure takes into
account chronic dietary food and water (considered to be a background
exposure level) plus indoor and outdoor residential exposure. The
potential short-term and intermediate-term aggregate risk for the U.S.
population is an exposure of approximately 0.0082 mg/kg/day with an MOE
of approximately 244.
    It is important to acknowledge that these MOEs are likely to
significantly underestimate the actual MOEs due to a variety of
conservative assumptions and biases inherent in the exposure assessment
methods used for their derivation. Therefore, it can be concluded that
the potential non-dietary and dietary aggregate exposures for
esfenvalerate are associated with a substantial degree of safety. EPA
has previously determined (62 FR 63019) that there was reasonable
certainty that no harm will result from aggregate exposure to
esfenvalerate residues. Head lettuce was included in that risk
assessment.

D. Cumulative Effects

    Section 408(b)(2)(D)(v) requires that, when considering whether to
establish, modify, or revoke a tolerance, the Agency consider
"available information" concerning the cumulative effects of a
particular pesticide's residues and "other substances that have a
common mechanism of toxicity." In a final rule on esfenvalerate (62 FR
63019) EPA concluded, "available information" in this context might
include not only toxicity, chemistry, and exposure data, but also
scientific policies and methodologies for understanding common
mechanisms of toxicity and conducting cumulative risk assessments. For
most pesticides, although the Agency has some information in its files
that may turn out to be helpful in eventually determining whether a
pesticide shares a common mechanism of toxicity with any other
substances, EPA does not at this time have the methodologies to resolve
the complex scientific issues concerning common mechanism of toxicity
in a meaningful way. EPA has begun a pilot process to study this issue
further through the examination of particular classes of pesticides.
The Agency hopes that the results of this pilot process will increase
the Agency's scientific understanding of this question such that EPA
will be able to develop and apply scientific principles for better
determining which chemicals have a common mechanism of toxicity and
evaluating the cumulative effects of such chemicals. The Agency
anticipates, however, that even as its understanding of the science of
common mechanisms increases, decisions on specific classes of chemicals
will be heavily dependent on chemical-specific data, much of which may
not be presently available.
    Although at present the Agency is not certain how to apply the
information in its files concerning common mechanism issues to most
risk assessments, there are pesticides for which common mechanism
issues can be resolved. These pesticides include those that are
toxicologically dissimilar to existing chemical substances (in which
case the Agency can conclude that it is unlikely that a pesticide
shares a common mechanism of activity with other substances) and
pesticides that produce a common toxic metabolite (in which case common
mechanism of activity will be assumed). Although esfenvalerate is
similar to other members of the synthetic pyrethroid class of
insecticides, EPA does not have, at this time, available data to
determine whether esfenvalerate has a common method of toxicity with
other substances or how to include this pesticide in a cumulative risk
assessment. Unlike other pesticides for which EPA has followed a
cumulative risk approach based on a common mechanism of toxicity,
esfenvalerate does not appear to produce a toxic metabolite produced by
other substances. For the purposes of this tolerance action, therefore,
EPA has not assumed that esfenvalerate has a common mechanism of
toxicity with other substances.

E. Safety Determination

    1. U.S. population. Both the chronic and acute toxicological
endpoints are derived from maternal NOAELs of 2.0 mg/kg/day in
developmental studies in rats and rabbits. There were no fetal effects.
In addition, no other studies conducted with fenvalerate or
esfenvalerate indicate that immature animals are more sensitive than
adults. Therefore, the safety factor used for protection of adults is
fully appropriate for the protection of infants and children; no
additional safety factor is necessary as described below. A chronic
dietary exposure assessment using anticipated residues, monitoring
information, and percent crop treated indicated the percentage of the
RfD utilized by the general population to be 2.0%. There is generally
no concern for exposures below 100% of the RfD because the RfD
represents the level at or below which daily aggregate dietary exposure
over a lifetime will not pose appreciable risks to human health.
    For acute exposure, a MOE greater than 100 is considered adequate.
A Tier 3 acute dietary exposure assessment found the general population
to have MOEs of 355 and 171 at the 99th and
99.9th percentile of exposure, respectively. These values
were generated using actual field trial residues and market share data
for percentage of crop treated. These results depict an accurate
exposure pattern at an exaggerated daily dietary exposure rate.
    Short-term and intermediate-term aggregate exposure risk from
chronic dietary food and water plus indoor and outdoor residential
exposure for the U.S. population is an exposure of approximately 0.0082
mg/kg/day with an MOE of approximately 244.
    Therefore, there is a reasonable certainty that no harm will result
from chronic dietary, acute dietary, non-dietary, or aggregate exposure
to esfenvalerate residues.
    2. Infants and children. FFDCA section 408 provides that EPA shall
apply an additional ten-fold margin of safety for infants and children
unless EPA determines that a different margin of safety will be safe
for infants and children. EPA has stated that reliable data support
using the standard MOE and UF (100 for combined interspecies
and intraspecies variability) and not the additional ten-fold MOE/UF
when EPA has a complete data base under existing guidelines and when
the severity of the effect in infants or children or the potency or
unusual toxic properties of a compound do not raise concerns regarding
the adequacy of the standard MOE/safety factor. In a final rule (62 FR
63019), EPA concluded that reliable data support use of the standard
100-fold UF for esfenvalerate, and that an additional UF is not needed
to protect the safety of infants and children. This decision was based
on no evidence of developmental toxicity at doses up to 20 mg/kg/day
(ten times the maternal NOAEL) in prenatal developmental toxicity
studies in both rats and rabbits; toxicity to offspring only at dietary
levels which were also found to be toxic to parental animals in the 2-
generation reproduction study; and no evidence of additional
sensitivity to young rats or rabbits following prenatal or postnatal
exposure to esfenvalerate.
    A chronic dietary exposure assessment found the percentages of the
RfD utilized by the most sensitive subpopulation to be 4.8% for
children 1 to 6 years based on a dietary exposure of 0.000957 mg/kg/
day. The percent RfD for children 7 to 12 years was 3.0%. The Agency
has no cause for concern if RfDs are below 100%.
    The most sensitive subpopulation, children 1 to 6 years, had acute
dietary MOEs of 202 and 103 at the 99th and
99.9th percentile of exposure, respectively. Nursing infants
had MOEs of 195 and 146 at the 99th and 99.9th
percentile of exposure, respectively. Non-nursing infants had MOEs of
304 and 158 at the 99th and 99.9th percentile of
exposure, respectively. The Agency has no cause for concern if total
acute exposure calculated for the 99.9th percentile yields
an MOE of 100 or larger. EPA has concluded that the potential short-
term or intermediate-term aggregate exposure of esfenvalerate from
chronic dietary food and water plus indoor and outdoor residential
exposure to children (1 to 6 years old) is 0.0113 mg/kg/day with an MOE
of 177. For infants (less than 1 year old) the exposure is 0.0098 mg/
kg/day with an MOE of 204. Thus, there is a reasonable certainty that
no harm will result to infants and children from aggregate exposure to
esfenvalerate residues (62 FR 63019).

F. International Tolerances

    Codex maximum residue levels (MRLs) have been established for
residues of fenvalerate on a number of crops that also have U.S.
tolerances. There are some minimal differences between the section 408
tolerances and certain Codex MRL values. These differences could be
caused by differences in methods to establish tolerances, calculate
animal feed, dietary exposure, and as a result of different
agricultural practices. Therefore, some harmonization of these maximum
residue levels will be required.

[FR Doc. 01-7641 Filed 3-27-01; 8:45 am]
BILLING CODE 6560-50-S