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Esfenvalerate - Pesticide Petition Filing 4/98

[Federal Register: April 15, 1998 (Volume 63, Number 72)]
[Notices]
[Page 18411-18420]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr15ap98-90]
[[Page 18411]]
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ENVIRONMENTAL PROTECTION AGENCY
[PF-801; FRL-5781-9]
Notice of Filing of Pesticide Petitions
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice.
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SUMMARY: This notice announces the initial filing of pesticide
petitions proposing the establishment of regulations for residues of
certain pesticide chemicals in or on various food commodities.
DATES: Comments, identified by the docket control number PF-801, must
be received on or before May 15, 1998.
ADDRESSES: By mail submit written comments to: Public Information and
Records Integrity Branch, Information Resources and Services Division
(7502C), Office of Pesticides Programs, Environmental Protection
Agency, 401 M St., SW., Washington, DC 20460. In person bring comments
to: Rm. 119FF, CM #2, 1921 Jefferson Davis Highway, Arlington, VA.
    Comments and data may also be submitted electronically by following
the instructions under "SUPPLEMENTARY INFORMATION." No confidential
business information 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
"Confidential Business Information" (CBI). CBI should not be
submitted through e-mail. Information marked as CBI 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
may be disclosed publicly by EPA without prior notice. All written
comments will be available for public inspection in Rm. 1132 at the
address given above, from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays.

FOR FURTHER INFORMATION CONTACT: The product manager listed in the
table below:

------------------------------------------------------------------------
                                   Office location/

        Product Manager            telephone number          Address
------------------------------------------------------------------------
Sidney Jackson (PM 5).........  Rm. 268, CM #2, 703-    1921 Jefferson
                                 305-7610, e-            Davis Hwy,
                                 mail:jackson.sidney@e   Arlington, VA
                                 pamail.epa.gov.
Bipin Gandhi (PM 5)...........  Rm. 4W53, CS #2, 703-   Do.
                                 308-8380, e-mail:
                                 gandhi.bipin@epamail.
                                 epa.gov.
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SUPPLEMENTARY INFORMATION: EPA has received pesticide petitions as
follows proposing the establishment and/or amendment of regulations for
residues of certain pesticide chemicals in or on various food
commodities under section 408 of the Federal Food, Drug, and Comestic
Act (FFDCA), 21 U.S.C. 346a. EPA has determined that these petitions
contain 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.
    The official record for this notice of filing, as well as the
public version, has been established for this notice of filing under
docket control number [PF-801] (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 address in
"ADDRESSES" at the beginning of this document.
    Electronic comments can be sent directly to EPA at:
    opp-docket@epamail.epa.gov

    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 file format or ASCII
file format. All comments and data in electronic form must be
identified by the docket number FRL-5781-9 and appropriate petition
number. Electronic comments on notice may be filed online at many
Federal Depository Libraries.

List of Subjects

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

Dated: April 1, 1998

    James Jones,

Director, Registration Division, Office of Pesticide Programs.

Summaries of Petitions

    Petitioner summaries of the pesticide petitions are printed below
as required by section 408(d)(3) of the FFDCA. The summaries of the
petitions were prepared by the petitioners and represent the views of
the petitioners. EPA is publishing the petition summaries verbatim
without editing them 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.

2. Interregional Research Project

PP Nos. 6E3404, 6E4685, 1E3966, 9E3697, and 5E4580

    EPA has received pesticide petitions (PP Nos. 6E3404,
6E4685,1E3966, 9E3697, and 5E4580) from the Interregional Research
Project Number 4 (IR-4), proposing pursuant to section 408(d) of the
Federal Food, Drug and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to
amend 40 CFR part 180 tolerances for residues of esfenvalerate, (S)-
cyano-(3-phenoxyphenyl)methyl (S)-4-chloro-alpha-(1-methylethyl)
benzeneacetate in or on the raw agricultural commodities mustard greens
at 5 ppm (PP 6E3404), kiwifruit at 0.5 ppm (PP 6E4685), globe artichoke
at 1.0 ppm (PP 1E3966), cranberry at 0.2 ppm (PP 9E3697), and kohlrabi
at 2.0 ppm (PP 5E4580). EPA has determined that these petitions contain
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 submitted data at this time or whether these data
support granting the proposed tolerances. Additional data may be needed
before EPA rules on the petitions. This notice contains a summary of
the petitions submitted by DuPont Agricultural Products, the
registrant.

A. Residue Chemistry

    1. Plant metabolism. The metabolism and chemical nature of residues
of fenvalerate in plants and animals are adequately understood. The
fate of fenvalerate has been extensively studied using radioactive
tracers in plant and animal metabolism/nature of the residue studies.
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 with nitrogen phosphorous
detection available for enforcement with a limit of detection that
allows monitoring food with residues at or above tolerance levels. The
limit of detection for updated method is the same as that of the
current PAM II, which is 0.01 ppm.
    3. Magnitude of residues. Fenvalerate is a racemic mixture of four
isomers (about 25% each). Technical Asana (the S,S-isomer enriched
formulation, esfenvalerate), has been the only fenvalerate formulation
sold in the U.S. for agricultural use. Since the S,S-isomer is the
insecticidally active isomer, the use rate for Asana® is 4
times lower than that for Pydrin®. A petition is pending (PP
4F4329), to convert tolerances (still to be expressed as the sum of all
isomers) based on the use rates for Asana®. Bridging residue
studies have shown Asana® residues to be 3-4 times lower than
Pydrin® residues.

B. Toxicological Profile

    1. Acute toxicity. A battery of acute toxicity studies places
technical esfenvalerate in Toxicity Category II for acute oral toxicity
(rat lethal dose LD50 87.2 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 (a.i.) was waived due to negligible vapor pressure. A dermal
sensitization test on esfenvalerate in guinea pigs showed no
sensitization.
    2. Genotoxicity. Esfenvalerate was not mutagenic in reverse
mutation assays in S. typhimurium and E. coli and did not induce
mutations Chinese hamster V79 cells or chromosome aberrations in
Chinese hamster ovary cells. Esfenvalerate did not induce micronuclei
in bone marrow of mice given up to 150 mg/kg intra peritoneally.
Esfenvalerate did not induce unscheduled deoxyribonucleic acid (DNA)
synthesis 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
NOEL of 2 mg/kg/day was established for the pilot study. The
developmental NOEL 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 NOEL of 2 mg/kg/day was established on the

[[Page 18415]]

pilot study. The developmental NOEL 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 NOEL 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 NOEL 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 90-day feeding study in mice was conducted at 0, 50, 150, and 500
ppm esfenvalerate with a NOEL of 150 ppm (30.5 mg/kg) based on clinical
signs of toxicity at 500 ppm (106 mg/kg).
    A 3-month subchronic study in dogs was satisfied by a 1-year oral
study in dogs, in which the NOEL was 200 ppm (5 mg/kg/day).
    A 21-day dermal study in rabbits with fenvalerate conducted at 100,
300, and 1,000 mg/kg/day with a no-observed-adverse effect level
(NOAEL) of 1,000 mg/kg/day.
    5. Chronic toxicity. In a 1-year study, dogs were fed 0, 25, 50, or
200 ppm esfenvalerate with no treatment related effects at any dietary
level. The NOEL was established at 200 ppm (5 mg/kg/day). An effect
level for dietary administration of esfenvalerate for dogs of 300 ppm
had been established earlier in a three 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 NOEL 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 NOEL 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 NOEL is 100 ppm (15.0 mg/kg/day)
based on fenvalerate-related microgranulomatous changes at 300 ppm (45
mg/kg/day). No compound related carcinogenicity occurred.
    Mice were fed 0, 10, 30, 100, or 300 ppm fenvalerate for 20-months.
The NOEL 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 NOEL 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 non-
carcinogenicity for humans.
    6. Animal metabolism. In animal studies, after oral dosing with
radioactive 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.

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 recently (August 2, 1997) reviewed
the existing toxicology data base for esfenvalerate and selected the
following toxicological endpoints. For acute toxicity, EPA established
a NOEL of 2.0 mg/kg/day from rat and rabbit developmental studies based
on maternal clinical signs at higher concentrations. An 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
NOEL of 2.0 mg/kg/day in the rat developmental study with an
uncertainty factor of 100. Esfenvalerate is classified as a Group E
carcinogen - no evidence of carcinogenicity in either rats or mice.
Therefore, a carcinogenicity risk analysis for humans is not required.
    2. Food. A chronic dietary exposure assessment was conducted using
Novigen's DEEM (Dietary Exposure Estimate Model). 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 1-6 years, was 4.6% based on a
daily dietary exposure of 0.000911 mg/kg/day. Chronic exposure for the
overall US 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 mustard greens, kiwifruit, globe
artichoke, cranberry, and kohlrabi) 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.
    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. These data
are considered 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 1-6 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. The EPA has stated there is no cause for concern if
total acute exposure

[[Page 18416]]

calculated for the 99.9th percentile yields an MOE of 100 or larger.
This acute dietary exposure estimate is considered conservative and EPA
considered the MOEs adequate in a recent final rule published in the
Federal Register at 62 FR 63019 (November 26, 1997) (FRL-5781-1).
    3. Drinking water. Esfenvalerate is immobile in soil and will not
leach into groundwater. 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
PRZM3 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, DuPont believes that there is reasonable certainty of no
harm 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 deg. C.) and low dermal
penetration, would result in minimal inhalation and dermal exposure.
    To assess risk from (nonfood) short and intermediate term exposure,
EPA has recently selected a toxicological endpoint of 2.0 mg/kg/day,
the NOEL 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 NOEL 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- and
intermediate-tern 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 1-6 years and 0.00138 mg/kg/day for infants less than
1-year old.
    EPA concluded in the final rule published in the Federal Register
at 62 FR 63019 (November 26, 1997) that the potential non-dietary
exposure for esfenvalerate are associated with substantial margins of
safety.
    5. Aggregate exposure dietary and non dietary. EPA has concluded
that aggregate chronic exposure to esfenvalerate from food and drinking
water will utilize 1.9% of the RfD for the U.S. population based on a
dietary exposure of 0.000377 mg/kg/day. The major identifiable subgroup
with the highest aggregate exposure are children 1-6 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- 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- and intermediate-term aggregate risk for the U.S. population is
an exposure of 0.0082 mg/kg/day with an MOE of 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 in the final rule published in the Federal
Register at 62 FR 63019 (November 26, 1997) 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 recent final rule on esfenvalerate
published in the Federal Register at 62 FR 63019 (November 26, 1997)
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

[[Page 18417]]

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 does not know how to apply the
information in its files concerning common mechanism issues to most
risk assessments, there are pesticides as to which the common mechanism
issues can be resolved. These pesticides include pesticides 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. 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 1.9%. 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 of greater than 100 is considered an
adequate MOE. A Tier 3 acute dietary exposure assessment found the
General Population to have MOE's 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- 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 0.0082 mg/kg/day with an MOE of
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 tenfold 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 uncertainty factor (100 for combined inter-
and intra-species variability) and not the additional tenfold MOE/
uncertainty factor 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
recent final rule published in the Federal Register at 62 FR 63019
(November 26 1997), EPA concluded that reliable data support use of the
standard 100-fold uncertainty factor for esfenvalerate, and that an
additional uncertainty factor is not needed to protect the safety of
infants and children. This decision was based on, no evidence of
developmental toxicity at a doses up to 20 mg/kg/day (ten times the
maternal NOEL) in prenatal developmental toxicity studies in both rats
and rabbits; offspring toxicity 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 pre- or postnatal exposure to esfenvalerate.
    A chronic dietary exposure assessment found the percentages of the
RfD utilized by the most sensitive sub-population to be 4.6% for
children 1-6 years based on a dietary exposure of 0.000912 mg/kg/day.
The % RfD for nursing and non-nursing infants was 1.1% and 2.7%,
respectively. The Agency has no cause for concern if RfD are below
100%.
    The most sensitive sub-population, children 1-6 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 a MOE of 100
or larger.
    EPA has recently concluded that the potential short- or
intermediate-term aggregate exposure of esfenvalerate from chronic
dietary food and water plus indoor and outdoor residential exposure to
children (1-6 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 published in the Federal Register at 62 FR 63019 (November 26,
1997) (FRL-5754-6).

F. International Tolerances

    Codex maximum residue levels (MRL's) 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 for specific commodities. 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 may be required.

[FR Doc. 98-9395 Filed 4-14-98; 8:45 am]
BILLING CODE 6560-50-F