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Notice of Filing of Pesticide Petitions
Note: EPA no longer updates this information, but it may be useful as a reference or resource.
[Federal Register: September 17, 1997 (Volume 62, Number 180)]
[Notices]
[Page 48856-48859]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr17se97-69]
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ENVIRONMENTAL PROTECTION AGENCY
[PF-763; FRL-5742-9]
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-763, must
be received on or before October 17, 1997.
ADDRESSES: By mail submit written comments to: Public Information and
Records Integrity Branch (7506C), Information Resources and Services
Division, Office of Pesticides Programs, Environmental Protection
Agency, 401 M St., SW., Washington, DC 20460. In person bring comments
to: Rm. 1132, 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: By mail: Beth Edwards, Registration
Division (7505C), Office of Pesticide Programs, Environmental
Protection Agency, 401 M St., SW., Washington, DC 20460. Office
location and telephone number: Rm. 206, CM #2, 1921 Jefferson Davis
Highway, Arlington, VA 22202, (703) 305-5400; e-mail:
edwards.beth@epamail.epa.gov.
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 supports 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-763] (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 [pf-763] and appropriate petition
number. Electronic comments on this notice may be filed
[[Page 48857]]
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:September 8,1997
James Jones, Acting
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.
E.I. duPont de Nemours & Co.
PP 7F4859
EPA has received a pesticide petition (PP 7F4859) from E.I. duPont
de Nemours & Co.(DuPont), P.O. Box 80038, Wilmington, DE 19880-0038,
proposing pursuant to section 408(d) of the Federal Food, Drug and
Cosmetic Act, 21 U.S.C. 346a(d), to amend 40 CFR part 180 by
establishing a tolerance for residues of esfenvalerate, (Asana XL
Insecticide), ((S)-cyano-(3-phenoxyphenyl)methyl (S)-4-chloro-alpha-(1-
methylethyl) benzeneacetate in or on the raw agricultural commodity,
pistachios. The enforcement analytical method for determining residues
is gas chromatography with nitrogen phosphorus detection. 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 supports granting of the petition. Additional data
may be needed before EPA rules on the petition.
A. Residue Chemistry
1. Plant metabolism. The metabolism and chemical nature of residues
of fenvalerate in plants 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.
2. Analytical method. There is a practical analytical method
utilizing electron-capture gas chromotography (MRID No. 43567101)
available for enforcement with a limit of detection that allows
monitoring food with residues at or above tolerance levels.
3. Magnitude of residues. Current tolerances are based on the sum
of all isomers of fenvalerate. Fenvalerate is a racemic mixture of four
isomers (about 25% each). This product was registered as Pydrin.
However, since 1992, an S,S-isomer enriched formulation, Asana
(esfenvalerate), has been the only fenvalerate formulation sold in the
U.S. 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-34F4329), to convert tolerances based on the use rates for
Asana (still to be expressed as the sum of all isomers). Bridging
studies have shown Asana residues to be 3-4 times lower than Pydrin
residues.
A magnitude of residue study on pistachio was conducted at 5 sites
in California where climate, soil type, and other conditions are
typical of those found where Asana may be used on pistachio nuts for
insect control. At each site, Asana was applied 2 times at 0.10 lb ai/A
by foliar broadcast spray, 7 days apart, for a maximum rate of 0.20 lb
ai/A/season. Treatments were also made at twice the maximum proposed
label rate at each site. Pistachio samples were collected 0 and 1 day
after the last application. The mean esfenvalerate residue found at the
proposed label rate of 0.20 lb ai/A/season with a PHI of 1 day was
0.031 ppm +/- 0.012 ppm. These results support the proposed tolerance
of 0.10 ppm.
Since there are no processed commodities of pistachios, processing
studies were not conducted. In addition, pistachios are not an animal
feed item and, therefore, secondary residues will not be an issue.
B. Toxicological Profile
The following studies have been submitted to EPA:
1. Acute toxicity. A rat acute oral study on esfenvalerate
technical with an LD50 of 87.2 mg/kg (MRID 00144973). A
rabbit acute dermal study on esfenvalerate with an LD50 of
>2000 mg/kg (MRID 00156508). Acute inhalation on technical grade a.i.
waived due to negligible vapor pressure. A primary eye irritation test
using esfenvalerate in the rabbit which showed mild irritation
(conjunctivitis) that cleared by day 7 (MRID 00156509). A primary
dermal irritation test using esfenvalerate in the rabbit which showed
minimal irritation that reversed within 72 hours after treatment (MRID
00156510). A dermal sensitization test on esfenvalerate in guinea pigs
which showed no sensitization (MRID 41215203).
2. Genotoxicity. Esfenvalerate was not mutagenic in reverse
mutation assays in Salmonella and E. Coli (MRID 413163010) or in HGPRT
in vitro assay in Chinese hamster lung cells (MRID 41316302).
Esfenvalerate did not induce chromosome aberrations in an in vitro
assay in Chinese hamster ovary cells (MRID 41215204). Esfenvalerate did
not induce micronuclei in bone marrow of mice given up to 150 mg/kg
intraperitoneally (MRID 41316303). Esfenvalerate did not induce
unscheduled DNA synthesis in HeLa cells (MRID 41316304).
3. Reproductive and developmental toxicity. A pilot developmental
study in the rat with doses of 0, 1, 2, 3, 4, 5, and 20 mg/kg/day
esfenvalerate (MRID 43211502). The maternal NOEL was 3 mg/kg/day based
on maternal clinical signs of abnormal gait or mobility at 4 mg/kg/day
and above. A developmental study in the rat with doses of 0, 2.5, 5,
10, and 20 mg/kg/day esfenvalerate by gavage (MRID 43211504). There was
no maternal NOEL but a maternal NOEL was established in the pilot
study. Maternal signs observed at 2.5 mg/kg/day were erratic jerking
and extension of forelimbs, rapid side-to-side head movement and
excessive grooming. There were no fetal or developmental effects in
either study at 20 mg/kg/day, the highest dose tested. Therefore, the
fetal/developmental NOEL was >20 mg/kg/day.
A pilot developmental study in the rabbit with doses of 0, 2, 3, 4,
4.5, 5, and 20 mg/kg/day esfenvalerate by gavage (MRID 43211501). The
maternal NOEL was 2 mg/kg/day based on excessive grooming at 3 mg/kg/
day and above. A developmental study in the rabbit with doses of 0, 3,
10, and 20 mg/kg/day esfenvalerate by gavage (MRID 43211503). There was
no maternal NOEL but a maternal NOEL was established in the pilot
study. There were no fetal or developmental effects in either study at
the highest dose tested. Therefore, the fetal/developmental NOEL was
>20 mg/kg/day.
A 2-generation feeding study with esfenvalerate in the rat at
dietary levels of 0, 75, 100, or 300 ppm. The high
[[Page 48858]]
dietary concentration was lowered to 150 ppm for the second generation.
Very mild body weight effects and sores at 75 ppm in both generations
were considered secondary effects caused by scratching related to skin
stimulation from dermal exposure. Therefore 75 ppm (4.2 mg/kg/day for
first generation parental males, 5.6 mg/kg/day for first generation
parental females, 6.0 mg/kg/day for second generation parental males,
and 7.3 mg/kg/day for second generation parental females) was
considered an NOAEL for both adult rats and their offspring. Effects
were observed in adults and pups of both generations at 100 ppm and
above. Pups were no more sensitive than adult animals (MRID 43489001).
4. Subchronic toxicity. A 90-day feeding study in rats conducted at
0, 75, 100, 125, and 300 ppm esfenvalerate with a NOEL of 125 ppm (6.3
mg/kg/day). This study provided intermediate dose levels to supplement
a 90-day feeding study in rats conducted at 0, 50, 150, 300 and 500 ppm
esfenvalerate with a NOEL of 50 ppm (2.5 mg/kg/day) based on jerky leg
movements at 150 ppm (7.5 mg/kg/day) and above (MRID 00151030).
A 90-day feeding study in mice conducted at 0, 50, 150, and 500 ppm
esfenvalerate and 2,000 ppm fenvalerate with a NOEL of 50 ppm
esfenvalerate (10.5 mg/kg/day) based on lower glucose and triglycerides
at 150 ppm. Neurologic symptoms were observed with 500 ppm
esfenvalerate and 2,000 ppm fenvalerate (MRID 41359701).
Three month subchronic study in dogs is satisfied by 1-year oral
study in dogs, in which the NOEL was 200 ppm (5 mg/kg/day) (MRID's
00265247, 403375601, and 40799501).
A 21-day dermal study in rabbits with fenvalerate conducted at 100,
300, and 1,000 mg/kg/day of fenvalerate with an NOEL of 1,000 mg/kg/day
fenvalerate (MRID 42325101).
5. Chronic toxicity. A 1-year study in which dogs were fed 0, 25,
50, or 200 ppm esfenvalerate with no treatment related effects at any
dietary level. The NOEL was 200 ppm (5 mg/kg/day). (MRID's 00265247,
40375601, 40799501). An effect level for dietary administration of
esfenvalerate for dogs of 300 ppm had been established earlier in the
2-week pilot study used to select dose levels for the chronic dog study
(MRID 40376501).
A 20-month study with fenvalerate in mice fed 0, 10, 30, 100, and
300 ppm fenvalerate. The NOEL was 30 ppm (6mg/kg/day) based on red
blood cell effects and granulomatous changes at 100 ppm. Fenvalerate
was not carcinogenic at any concentration (MRID 00093662).
An 18-month study with esfenvalerate in mice fed 0, 35, 150, and
350 ppm esfenvalerate. Mice fed the 350 ppm dose were sacrificed within
the first 2 months of the study, after excessive morbidity and
mortality due to self-trauma induced by pharmacological effects on
dermal sensory nerves. Therefore, data collected from the 350 ppm group
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 was not carcinogenic at either the 35
ppm or 150 ppm concentrations (MRID 44260601).
A 2-year study with fenvalerate in rats fed 1, 5, 25, and 250 ppm.
A 1,000 ppm group was added to establish an effect level. The NOEL was
250 ppm (12.5 mg/kg/day). At 1,000 ppm, hind limb weakness, lower body
weight, and higher organ-to-body weight ratios were observed.
Fenvalerate was not carcinogenic at any concentration (MRID's 00079877,
00082007).
6. Animal metabolism. After oral dosing, fenvalerate was eliminated
from rats within 5 days after dosing. 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 which needs regulation in plant and animal
commodities.
8. Other potential toxicology considerations - endocrine effects.
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.
C. Aggregate Exposure
1. Dietary exposure. For purposes of assessing dietary exposure,
chronic and acute dietary assessments have been conducted using all
existing and pending tolerances for esfenvalerate. The toxocological
endpoints used in both dietary assessments are derived from maternal
NOEL's of 2.0 mg/kg/day from rat and rabbit teratology studies. There
were no fetal effects.
2. Food. A chronic dietary exposure assessment using anticipated
residues and assuming that 100% of all crops are treated, found the
percentages of the Reference Dose (RfD) utilized by the two most
sensitive sub-populations to be 44% (Non-Nursing Infants <1 yr.) and
48% (Children 1-6 yrs.). This assessment also included all food
tolerances for incidental food handling establishments which were set
at 0.05 ppm (the limit of quantitation) since there were no detectable
residues. The results have been adjusted from the study previously
submitted (MRID 43639301) to reflect the new Reference Dose (RfD)
selected by EPA.
The Tier 3 acute dietary assessment has been rerun to incorporate
current EPA thinking on processing studies and secondary residues that
has arisen since the original study was submitted (MRID 44197701). The
most sensitive sub-populations were determined to be: Non-Nursing
Infants (< 1 yr.) with a Margin of Exposure (MOE) of 914 at the
95th percentile of exposure and an MOE of 254 at the
99th percentile of exposure; and Children (1-6 yrs.) with an
MOE of 698 at the 95th percentile of exposure and 321 at the
99th percentile. The MOE's for the general population were
1,803 at the 95th percentile of exposure and 676 at the
99th percentile. This analysis used field trial residue data
and market share data for the percent of crop treated. It also used
Monte Carlo sampling and applied appropriate processing factors for
apple juice and apple juice concentrate. Monte Carlo distribution was
also used for meat and milk residues. Food handling establishment
commodities were not included in the analysis because EPA methodology
does not include them in Tier 3 exposure modeling.
3. Drinking water. Esfenvalerate is immobile in soil and,
therefore, will not leach into groundwater. Additionally, 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. In addition, a screening evaluation of
leaching potential of esfenvalerate has been conducted using DuPont's
Tier 1 Ground Water Exposure Model (TIGEM, Version 12/30/96) which is
based on results from EPA's Pesticide Root Zone Model (PRZM, Version
2.0). Based on this screening
[[Page 48859]]
assessment, the potential concentrations of esfenvalerate in shallow
ground water are judged to be negligible.
4. Non-dietary exposure. Dietary exposure is the only significant
route of chronic non-occupational exposure to esfenvalerate. However,
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.
D. Cumulative Effects
The potential for cumulative effects of esfenvalerate and other
pyrethroid insecticides that have a common mechanism of toxicity must
also be considered. While risk assessment methodology has not been
developed to estimate cumulative exposure to multiple pyrethroids,
their similar insecticidal efficacy results in the substitution of one
pyrethroid for another, rather than addition of pyrethroids. Because of
the breadth of exposures included in the assumptions for esfenvalerate
risk assessment, it is unlikely that there will be significant additive
exposure to other pyrethroids.
These issues are extremely complex and require an extensive
evaluation of a wealth of proprietary and published data across a broad
range of pyrethroid insecticides in order to provide a scientifically
sound interpretation upon which to base any regulatory judgments. The
Pyrethroid Working Group is currently awaiting guidance from the Agency
on cumulative effects. They anticipate having some preliminary
evaluation data available for the Agency by August, 1997. For any
interim decisions, the Agency should take into consideration the
relatively benign toxicological profiles of pyrethroid insecticides and
their long history of safe use.
E. Safety Determination
Both the chronic and acute toxicological endpoints are derived from
maternal NOEL's of 2.0 mg/kg/day in developmental studies in rats and
rabbits. There were no fetal effects. 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.
1. U.S. population. A chronic dietary exposure assessment using
anticipated residues and assuming that 100% of all crops are treated,
found the percentage of the Reference Dose (RfD) utilized by the
General Population to be 16%. 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. Therefore, there is a
reasonable certainty that no harm will result from aggregate exposure
to esfenvalerate residues.
A Tier 3 acute dietary exposure assessment found the General
Population to have MOE's of 1,803 at the 95th percentile of
exposure and 676 at the 99th percentile of exposure. 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. Thus, there is a reasonable certainty that no harm will result
from aggregate exposure to esfenvalerate residues.
2. Infants and children. The chronic dietary assessment using the
same assumptions described above, found the two most sensitive sub-
populations to be non-nursing infants (<1 yr.) and children (1-6 yrs.)
utilizing 44% and 48% of the RfD, respectively. In the Tier 3 acute
dietary assessment that was rerun using the assumptions described
above, non-nursing infants were found to have an MOE of 914 at the
95th percentile of exposure and an MOE of 254 at the
99th percentile. Children (1-6 yrs.) were determined to have
an MOE of 698 at the 95th percentile and 321 at the
99th percentile. Therefore, there is a reasonable certainty
that no harm will result from aggregate exposure to esfenvalerate
residues.
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. Several of these MRL's are different than the proposed U.S.
tolerances for esfenvalerate. Therefore, some harmonization of these
maximum residue levels is still needed.
[FR Doc. 97-24691 Filed 9-16-97; 8:45 am]
BILLING CODE 6560-50-F