[Federal Register Volume 62, Number 180 (Wednesday, September 17, 1997)]
[Notices]
[Pages 48856-48859]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-24691]


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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: 
[email protected].

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:
    [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 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

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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