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Tefluthrin (Zeneca). September 25, 1997, Filing of Pesticide Petition. Federal Register.


Note from FAN:
We include only the petitions for organofluorine pesticides:

-- Cyfluthrin. BAYER: PP 4F3046, 9F3731, 3F4204, 4F4309, 4F4313, 2F4137, 4H5427, 9H5574, 3H5670, 4H5686, 4H5687
-- Bifenthrin. FMC: PP 6F3453, 7F3546, 5F4484, and 0E3921
-- lambda-Cyhalothrin: Zeneca: PPs 7F3560, 7H5543, 1F3952, 1H5607, 1F3991, 2F4109, 2F4100, 2F4114, 1F3985, and 6F4769
-- Tefluthrin: Zeneca: PP 7G3518, 7F3521, 4F4406

http://www.epa.gov/fedrgstr/EPA-PEST/1997/September/Day-25/p25499.htm

[Federal Register: September 25, 1997 (Volume 62, Number 186)]
[Notices]
[Page 50337-50367]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr25se97-68]

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ENVIRONMENTAL PROTECTION AGENCY

[PF-767; FRL-5748-2]

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-767, must
be received on or before October 27, 1997.
ADDRESSES: By mail submit written comments to: Public Information and
Records Integrity Branch, Information Resources and Services Division
(7506C), 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 to: opp-
docket@epamail.epa.gov. Follow 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: George LaRocca, Registration
Division [PM-13], Office of Pesticide Programs, 401 M St., SW.,
Washington, DC 20460. Office location, telephone number and e-mail
address: Rm. 204, Crystal Mall #2, 1921 Jefferson Davis Hwy.,
Arlington, VA, (703) 305-6100, e-mail: larocca.george@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-767] (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 controlnumber [PF-767] and appropriate
petition number. Electronic comments on this 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: September 19, 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.


2. Bayer Corporation

PP 4F3046, 9F3731, 3F4204, 4F4309, 4F4313, 2F4137, 4H5427, 9H5574,
3H5670, 4H5686, 4H5687

    EPA has received a request regarding pesticide petitions (PP
4F3046, 9F3731, 3F4204, 4F4309, 4F4313, 2F4137, 4H5427, 9H5574, 3H5670,
4H5686, 4H5687) from Bayer Corporation, 8400 Hawthorn Road, P.O. Box
4913, Kansas City, MO 64210 to remove the time limitations on the
established tolerances at 40 CFR Sec. 180.436, Sec. 185.1250 and
Sec. 186.1250 for the insecticide cyfluthrin, [cyano[4-fluoro-3-
phenoxyphenyl]-methyl-3-[2,2-dicloroethenyl]-2,2-dimethyl-
cyclopropanecarboxylate] in or on the raw agricultural commodities
alfalfa, forage, at 5.0 ppm; alfalfa, hay, at 10.0 ppm; aspirated grain
fractions at 300 ppm; carrots at 0.2 ppm; cattle, fat, at 1.0 ppm;
cattle, meat, at 0.4 ppm; cattle, meat by-products (mbyp) at 0.4 ppm;
corn, forage (sweet), at 15.0 ppm; corn, fodder (sweet), at 30 ppm;
corn (sweet, K+CWHR), at 0.05 ppm; cottonseed at 1.0 ppm; cottonseed,
oil, at 2.0 ppm; cottonseed, hulls, at 2.0 ppm; citrus, whole fruit, at
0.2 ppm; citrus oil, at 0.3 ppm; citrus dried pulp, at 0.3 ppm; eggs at
0.01 ppm; goats, fat, at 1.0 ppm; goats, meat, at 0.4 ppm; goats, meat
by-products (mbyp) at 0.4 ppm; hogs, fat, at 1.0 ppm; hogs, meat, at
0.4 ppm; hogs, meat by-products (mbyp) at 0.4 ppm; horses, fat, at 1.0
ppm; horses, meat, at 0.4 ppm; horses, meat by-products (mbyp) at 0.4
ppm; milkfat, at 15.0 ppm (representing 0.5 ppm in whole milk);
peppers, at 0.5 ppm; poultry, fat, at 0.01 ppm; poultry, meat, at 0.01
ppm; poultry, meat by-products (mbyp) at 0.01 ppm; radishes at 1.0 ppm;
sheep, fat, at 1.0 ppm; sheep, meat, at 0.4 ppm; sheep, meat by-
products (mbyp) at 0.4 ppm; sorghum, fodder, at 5.0 ppm; sorghum,
forage, at 2.0 ppm; sorghum, grain at 4.0 ppm, sunflower, forage, at
1.0 ppm; sunflower, seed, at 0.02 ppm; sugarcane, at 0.05 ppm;
sugarcane, molasses, at 0.2 ppm; tomatoes, at 0.2 ppm; tomato,
concentrated products, at 0.5 ppm; and tomato, pomace (wet and dry) at
5.0 ppm. All data requested by EPA have been submitted. Therefore, a
request for unconditional registration and removal of the time
limitations on established tolerances is being made.
    Consistent with section 408(d) of FFDCA, as recently amended by the
Food Quality Protection Act, Bayer submitted a summary and
authorization for the summary to be published in the Federal Register
in a notice of receipt of the request. The summary represents the views
of Bayer; EPA is in the process of evaluating the request. Consistent
with section 408(d)(3), EPA is including the summary as a part of this
notice of filing. EPA has not fully evaluated the sufficiency of the
submitted data at this time or whether the data support granting the
request.

A. Residue Chemistry

    1. Plant metabolism. The metabolism of cyfluthrin in plants is
adequately understood. Studies have been conducted to delineate the
metabolism of radio labeled cyfluthrin in various crops all showing
similar results. The residue of concern is cyfluthrin.
    2. Analytical method. Adequate analytical methodology (gas/liquid
chromatography with an electron capture detector) is available for
enforcement purposes.
    3. Magnitude of residues. Cyfluthrin is the active ingredient in
the registered end-use product Baythroid 2 Emulsifiable Pyrethroid
Insecticide, EPA Reg. No. 3125-351. Baythroid 2 is registered for use
on alfalfa, carrots,

[[Page 50342]]

citrus, cotton, peppers, radishes, sorghum, sugarcane, sweet corn,
sunflowers and tomatoes.
    Tolerances to support these uses were proposed in pesticide
petitions 4F3046, 9F3731, 3F4204, 4F4309, 4F4313, 2F4137, and 4F4313
and food/feed additive petitions 4H5427, 9H5574, 3H5670, 4H5686, and
4H5687. Residue data covering all the uses associated with these
petitions have been previously submitted to EPA for review and have
been found by EPA to support the establishment of the tolerances.
Consequently, regulations establishing these tolerances were
promulgated in response to these petitions. See [53 FR 30676]
(cottonseed), [60 FR 28353] (carrots, radishes, peppers and tomatoes),
[60 FR 28353] (sugarcane), [61 FR 10678] (alfalfa, sunflowers, and
sweet corn), [61 FR 39883] (sorghum), and [62 FR 25518] (citrus).

B. Toxicological Profile

    The database for cyfluthrin is current and complete. Toxicology
data cited in support of these tolerances include:
    1. Acute toxicity. There is a battery of acute toxicity studies for
cyfluthrin supporting an overall toxicity Category II.
    2. Genotoxicty. Mutagenicity tests were conducted, including
several gene mutation assays (reverse mutation and recombination assays
in bacteria and a Chinese hamster ovary (CHO)/HGPRT assay); a
structural chromosome aberration assay (CHO/sister chromatid exchange
assay); and an unscheduled DNA synthesis assay in rat hepatocytes. All
tests were negative for genotoxicity.
    3. Reproductive and developmental toxicity. An oral developmental
toxicity study in rats with a maternal and fetal NOEL of 10 milligrams/
kilogram of body weight/day (mg/kg bw/day) (highest dose tested).
    An oral developmental toxicity study in rabbits with a maternal
NOEL of 20 mg/kg bw/day and a maternal Lowest Effect Level (LEL) of 60
mg/kg bw/day, based on decreased body weight gain and decreased food
consumption during the dosing period. A fetal NOEL of 20 mg/kg bw/day
and a fetal LEL of 60 mg/kg bw/day were also observed in this study.
The LEL was based on increased resorptions and increased
postimplantation loss.
    A three-generation reproduction study in rats with systemic
toxicity NOELs of 7.5 and 2.5 mg/kg bw/day for parental animals and
their offspring, respectively. At higher dose levels, the body weights
of parental animals and their offspring were reduced.
    4. Subchronic toxicity. A subchronic toxicity feeding study using
rats demonstrated a NOEL of 22.5 mg/kg bw/day, the highest dose tested.
    A 6-month toxicity feeding study in dogs established a NOEL of 5
mg/kg bw/day. The LEL was 15 mg/kg bw/day based on clinical signs and
reduced thymus weights.
    5. Chronic toxicity. A 12-month chronic feeding study in dogs
established a NOEL of 4 mg/kg bw/day. The lowest effect level (LEL) for
this study is established at 16 mg/kg bw/day, based on slight ataxia,
increased vomiting, diarrhea and decreased body weight.
    A 24-month chronic feeding/ carcinogenicity study in rats
demonstrated a NOEL of 2.5 mg/kg bw/day and LEL of 6.2 mg/kg bw/day,
based on decreased body weights in males, decreased food consumption in
males, and inflammatory foci in the kidneys in females.
    A 24-month carcinogenicity study in mice was conducted. Under the
conditions of the study there were no carcinogenic effects observed. A
24-month chronic feeding/carcinogenicity study in rats was conducted.
There were no carcinogenic effects observed under the conditions of the
study.
    6. Animal metabolism. A metabolism study in rats showed that
cyfluthrin is rapidly absorbed and excreted, mostly as conjugated
metabolites in the urine, within 48 hours. An enterohepatic circulation
was observed.
    7. Metabolite toxicology. No toxicology data have been required for
cyfluthrin metabolites. The residue of concern is cyfluthrin.
    8. Endocrine effects. There is no evidence of endocrine effects in
any of the studies conducted with cyfluthrin, thus, there is no
indication at this time that cyfluthrin causes endocrine effects.

C. Aggregate Exposure

    1. Dietary exposure-- Food. Dietary exposure was estimated using
Novigen's Dietary Exposure Evaluation Model (DEEMa) software; results
from field trial and processing studies; consumption data from the USDA
Continuing Surveys of Food Intake by Individuals (CSFIIs), conducted
from 1989 through 1992; and information on the percentages of the crop
treated with Cyfluthrin.
    Cyfluthrin is registered for use in alfalfa, citrus, sweet corn,
cotton, sorghum, sunflower, sugarcane, carrots, peppers, radishes and
tomatoes. In addition, it has an import tolerance for hops. Various
formulations are registered for use in food handling establishments and
in combination with another active ingredient, for use in field corn,
pop corn and sweet corn.
    Chronic dietary exposure estimates for the overall U.S. population
were 0.5% of the Reference dose (RfD) (0.008 mg/kg bw/day). For the
most highly exposed population subgroup, children 1 to 6 years of age,
the exposure was estimated to be 0.000062 mg/kg bw/day, or 0.8% of the
RfD. Acute dietary exposures were estimated for the overall US
population, females 13 years and older, children, ages 1-6 and 7-12
years, infants, non-nursing and nursing. The exposure was compared to
the NOEL of 20 mg/kg bw/day to estimate the Margins of Exposures
(MOEs).
    For the overall U.S. population the 95th, 99th and 99.9th
percentile of exposure the MOEs were calculated as 29,981; 9,519; and
3,658 respectively.
    For women aged 13 years and older the 95th, 99th and 99.9th
percentile of exposure the MOEs were calculcated as 45,996; 20,103 and
10,011 respectively.
    Lastly, for the potentially highest exposed population subgroup,
non-nursing infants, the 95th, 99th and 99.9th percentile of exposure
to the MOEs were calculated at 16,107; 3,072; and 1,343, respectively.
    2. Drinking water. Cyfluthrin is immobile in soil, therefore, will
not leach into groundwater. Additionally, due the insolubility and
lipophilic nature of cyfluthrin, 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 (PRZM3).
Based on this screening assessment, the potential concentrations of a
pyrethroid in ground water at 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 52 parts per trillion. Concentration in actual drinking water would
be much lower. Based on these analyses, the contribution of water to
the dietary risk estimate is negligible.
    3. Non-dietary exposure. Non-occupational exposure to cyfluthrin
may occur as a result of inhalation or contact from indoor residential,
indoor commercial, and outdoor residential uses. Pursuant to the
requirements of FIFRA as amended by the Food Quality Protection Act of
1996, non-dietary and aggregate risk analyses for cyfluthrin

[[Page 50343]]

were conducted. The analyses include evaluation of potential non-
dietary acute application and post-application exposures. Non-
occupational, non-dietary exposure was assessed based on the assumption
that a flea infestation control scenario represents a ``worst case''
scenario. For the flea control infestation scenario indoor fogger, and
professional residential turf same day treatments were included for
cyfluthrin. Deterministic (point values) were used to present a worse
case upper-bound estimate of non-dietary exposure. The non-dietary
exposure estimates were expressed as systemic absorbed doses for a
summation of inhalation, dermal, and incidental ingestion exposures.
These worst-case non-dietary exposures were aggregated with chronic
dietary exposures to evaluate potential health risks that might be
associated with cyfluthrin products. The chronic dietary exposures were
expressed as an oral absorbed dose to combine with the non-dietary
systemic absorbed doses for comparison to a systemic absorbed dose
(NOEL). Results for each potential exposed subpopulation (of adults,
children 1-6 years, and infants <1 year) were compared to the systemic
absorbed dose NOEL for cyfluthrin to provide estimates of MOE.
    The large MOEs for cyfluthrin clearly demonstrate a substantial
degree of safety. The total non-dietary MOEs are 3,800, 2,700, and
2,500 for adults, children (1-6 years), and infants (<1 year),
respectively. The aggregate MOE for adults is approximately 3,800 and
the MOEs for infants and children exceed 2,500.
    The non-dietary methods used in the analyses can be characterized
as highly conservative. This is due to the conservatism inherent in the
calculation procedures and input assumptions. An example of this is the
conservatism inherent in the jazzercise over representation of
residential post-application exposures. It is important to acknowledge
that these MOEs are likely to significantly underestimate actual MOEs
due to a variety of conservative assumptions and biases inherent in the
derivatization of exposure by this method. Therefore, it can be
concluded that large MOEs associated with potential non-dietary and
aggregate exposures to cyfluthrin will result in little or no health
risks to exposed persons. The aggregate risk analysis demonstrates
compliance with the health-based requirements of the Food Quality
Protection Act of 1996 and supports the continued registration and use
of residential, commercial, and agricultural products containing
cyfluthrin.

D. Cumulative Effects

    Further, Bayer does not have, at this time, available data to
determine whether cyfluthrin has a common mechanism of toxicity with
other substances. For the purposes of this tolerance action, therefore,
no assumption has been made that cyfluthrin has a common mechanism of
toxicity with other substances.
    Bayer will submit information for EPA to consider concerning
potential cumulative effects of cyfluthrin consistent with the schedule
established by EPA in the Federal Register of August 4, 1997, (62 FR
42020) and other EPA publications pursuant to the Food Quality
Protection Act.

E. Safety Determination

    1. U.S. population. Based on the exposure assessments described
above and on the completeness and reliability of the toxicity data, it
can be concluded that total aggregate exposure to cyfluthrin from all
uses will utilize less than 1% percent of the RfD for chronic dietary
exposures and that MOEs in excess of 1,000 exist for aggregate exposure
to cyfluthrin for non-occupational exposure. EPA generally has no
concerns for exposures below 100 percent of the RfD, because the RfD
represents the level at or below which daily aggregate exposure over a
lifetime will not pose appreciable risks to human health. Margins of
exposure of 100 or more (300 for infants and children) also indicate an
adequate degree of safety. Thus, it can be concluded that there is a
reasonable certainty that no harm will result from aggregate exposure
to cyfluthrin residues.
    2. Infants and children. In assessing the potential for additional
sensitivity of infants and children to residues of cyfluthrin, the data
from developmental studies in both rat and rabbit and a two-generation
reproduction study in the rat can be considered. The developmental
toxicity studies evaluate any potential adverse effects on the
developing animal resulting from pesticide exposure of the mother
during prenatal development. The reproduction study evaluates any
effects from exposure to the pesticide on the reproductive capability
of mating animals through two generations, as well as any observed
systemic toxicity.
    The toxicology data which support these tolerances include:
    An oral developmental toxicity study in rats with a maternal and
fetal NOEL of 10 mg/kg bw/day (HDT).
    An oral developmental toxicity study in rabbits with a maternal
NOEL of 20 mg/kg bw/day and a maternal LEL of 60 mg/kg bw/day, based on
decreased body weight gain and decreased food consumption during the
dosing period. A fetal NOEL of 20 mg/kg bw/day and a fetal LEL of 60
mg/kg bw/day were also observed in this study. The LEL was based on
increased resorptions and increased postimplantation loss.
    An oral developmental toxicity study performed with beta-
cyfluthrin, the resolved isomer mixture of cyfluthrin, has been
submitted to the Agency and is currently under review.
    A developmental toxicity study in rats exposed via inhalation to
liquid aerosols of cyfluthrin revealed developmental toxicity, but only
in the presence of maternal toxicity. The developmental NOEL was 0.46
mg/m3 on the basis of reduced placental and fetal weights,
and delayed ossification. The NOEL for overt maternal toxicity was <
0.46 mg/m3, the lowest dose tested (LDT).
    A three-generation reproduction study in rats with systemic
toxicity NOELs of 7.5 and 2.5 mg/kg bw/day for parental animals and
their offspring, respectively. At higher dose levels, the body weights
of parental animals and their offspring were reduced. Another multiple-
generation reproduction study in rats has been submitted to the Agency
and is currently under review.
    The Agency used the rabbit developmental toxicity study with a
maternal NOEL of 20 mg/kg bw/day to assess acute dietary exposure and
determine a MOE for the overall U.S. population and certain subgroups.
Since this toxicological endpoint pertains to developmental toxicity
the population group of concern for this analysis was women aged 13 and
above, the subgroup which most closely approximates women of child-
bearing age. The MOE is calculated as the ratio of the NOEL to the
exposure. The Agency calculated the MOE to be over 600. Generally,
MOE's greater than 100 for data derived from animal studies are
regarded as showing no appreciable risk.
    FFDCA section 408 provides that EPA may apply an additional safety
factor for infants and children in the case of threshold effects to
account for pre- and post-natal effects and the completeness of the
toxicity database.
    The results of the three-generation study in rats provided evidence
suggesting that, with respect to effects of cyfluthrin on body weight,
pups were more sensitive than adult rats. Thus, the Agency determined
that an additional 3-fold uncertainty factor (UF) should be used in
risk assessments to ensure adequate protection of infants and children.

[[Page 50344]]

    Generally, EPA considers MOEs of at least 100 to indicate an
adequate degree of safety. With an additional 3 x  uncertainty factor,
this would be 300 for infants and children. Using the exposure
assessments described above and based on the described toxicity data
aggregate exposure to infants and children indicate a MOE in excess of
2,500. Thus, it can be concluded that there is a reasonable certainty
that no harm will result to infants and children from aggregate
exposure to cyfluthrin residues.
    3. Conclusions. The available data indicate that there is
reasonable certainty of no harm from the aggregate exposure from all
currently registered uses of cyfluthrin. Thus, consistent with the
provisions of the FFDCA as amended August 3, 1996, the time limitations
on established cyfluthrin tolerance should be removed.

F. International Tolerances

    Codex maximum residue levels (MRLs) are established for residues of
cyfluthrin on milk (0.01 mg/kg); cottonseed (0.05 mg/kg); peppers,
sweet (0.2 mg/kg); and tomatoes (0.5 mg/kg). (Stephanie Willett)

...

6. FMC Corporation, Agricultural Products Group

PP 6F3453, 7F3546, 5F4484, and 0E3921

    EPA has received a request to remove the time limitations on
established tolerances from FMC Corporation, Agricultural Products
Group, 1735 Market Street, Philadelphia, Pennsylvania 19103 and from
the Interregional Research Project No. 4 (IR-4), New Jersey
Agricultural Experiment Station, P.O. Box 231, Rutgers University, New
Brunswick, NJ 08903. The request proposes to remove the time
limitations on established tolerances for residues of the insecticide
bifenthrin ((2-methyl [1,1'-biphenyl]-3-yl) methyl-3-(2-chloro-3,3,3,-
trifluoro-1-propenyl)-2,2-dimethylcyclopropanecarboxylate), in or on
the raw agricultural commodities cottonseed at 0.5 parts per million
(ppm); corn, grain (field, seed, and pop) at 0.05 ppm; hops, dried at
10.0 ppm; and strawberries at 3.0 ppm (established at 40 CFR 180.442).
These tolerances were established under [PP] 6F3453, 7F3546, 5F4484,
and 0E3921. EPA has determined that the request 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 requests. Additional data may be needed before EPA rules on the
requests.

A. Residue Chemistry

    1. Plant metabolism. The metabolism of bifenthrin in plants is
adequately understood. Studies have been conducted to delineate the
metabolism of radiolabeled bifenthrin in various crops all showing
similar results. The residue of concern is the parent compound only.
    2. Analytical method. There is a practical analytical method for
detecting and measuring levels of bifenthrin in or on food with a limit
of detection that allows monitoring of food with residues at or above
the levels set in these tolerances (Gas Chromatography with Electron
Capture Detection (GC/ECD) analytical method P-2132M.
    3. Magnitude of residues. Crop field trial residue data from
studies conducted at the maximum label rates for cotton; corn (field,
seed, pop); strawberries, and hops show that the established bifenthrin
tolerances on cottonseed of 0.5 ppm; corn, grain (field, seed, and pop)
of 0.05 ppm; corn, fodder of 5.0 ppm; corn, forage of 2.0 ppm;
strawberries of 3.0 ppm, and hops, dried of 10.0 ppm will not be
exceeded when the bifenthrin products labeled for these uses are used
as directed.

B. Toxicological Profile

    1. Acute toxicity. For the purposes of assessing acute dietary
risk, FMC has used the maternal NOEL of 1.0 mg/kg/day from the oral
developmental toxicity study in rats. The maternal LEL of this study of
2.0 mg/kg/day was based on tremors from day 7-17 of dosing. This acute
dietary endpoint is used to determine acute dietary risks to all
population subgroups.
    2. Genotoxicty. The following genotoxicity tests were all negative:
gene mutation in Salmonella (Ames); chromosomal aberrations in Chinese
hamster ovary and rat bone marrow cells; HGPRT locus mutation in mouse
lymphoma cells; and unscheduled DNA synthesis in rat hepatocytes.
    3. Reproductive and developmental toxicity-- a. Parental toxicity.
In the rat reproduction study, parental toxicity occurred as decreased
body weight at 5.0 mg/kg/day with a NOEL of 3.0 mg/kg/day. There were
no developmental (pup) or reproductive effects up to 5.0 mg/kg/day
(highest dose tested).
    b. Post-natal sensitivity. Based on the absence of pup toxicity up
to dose levels which produced toxicity in the parental animals, there
is no evidence of special post-natal sensitivity to infants and
children in the rat reproduction study.
    4. Subchronic toxicity. Short- and intermediate-term toxicity. The
maternal NOEL of 1.0 mg/ kg/day from the oral developmental toxicity
study in rats is also used for short- and intermediate-term margins of
exposure (MOE) calculations (as well as acute, discussed in (1) above).
The maternal lowest effect level (LEL) of this study of 2.0 mg/kg/day
was based on tremors from day 7-17 of dosing.
    5. Chronic toxicity--a. The reference dose (RfD) has been
established at 0.015 mg/kg/day. This RfD is based on a 1 year oral
feeding study in dogs with a NOEL of 1.5 mg/kg/day, based on
intermittent tremors observed at the Lowest Observed Effect Level
(LOEL) of 3.0 mg/kg/day; an uncertainty factor of 100 is used.
    b. Bifenthrin is classified as a Group C chemical (possible human
carcinogen) based upon urinary bladder tumors in mice; assignment of a
Q* has not been recommended.
    6. Animal metabolism. The metabolism of bifenthrin in animals is
adequately understood. Metabolism studies in rats with single doses
demonstrated that about 90% of the

[[Page 50353]]

parent compound and its hydroxylated metabolites are excreted.
    7. Metabolite toxicology. The Agency has previously determined that
the metabolites of bifenthrin are not of toxicological concern and need
not be included in the tolerance expression.
    8. Endocrine disruption. No special studies investigating potential
estrogenic or other endocrine effects of bifenthrin have been
conducted. However, no evidence of such effects were reported in the
standard battery of required toxicology studies which have been
completed and found acceptable. Based on these studies, there is no
evidence to suggest that bifenthrin has an adverse effect on the
endocrine system.

C. Aggregate Exposure

    1. Dietary exposure-- Food. Tolerances have been established for
the residues of bifenthrin, in or on a variety of raw agricultural
commodities. Tolerances, in support of registrations, currently exist
for residues of bifenthrin on hops; strawberries; corn grain, forage,
and fodder; cottonseed; and livestock commodities of cattle, goats,
hogs, horses, sheep, and poultry. Additionally, time-limited tolerances
associated with emergency exemptions were recently established for
broccoli, cauliflower, raspberries, cucurbits, and canola. A pending
tolerance for artichokes also exists. For the purposes of assessing the
potential dietary exposure for these existing and pending tolerances as
well as the existing time-limited tolerances under FIFRA section 18
emergency exemptions, FMC has utilized available information on
anticipated residues, monitoring data and percent crop treated as
follows:
    i. Acute exposure and risk. Acute dietary exposure risk assessments
are performed for a food-use pesticide if a toxicological study has
indicated the possibility of an effect of concern occurring as a result
of a 1 day or single exposure. For the purposes of assessing acute
dietary risk for bifenthrin, the maternal NOEL of 1.0 mg/kg/day from
the oral developmental toxicity study in rats was used. The maternal
LEL of this study of 2.0 mg/kg/day was based on tremors from day 7-17
of dosing. This acute dietary endpoint was used to determine acute
dietary risks to all population subgroups. Available information on
anticipated residues, monitoring data and percent crop treated was
incorporated into a Tier 3 analysis, using Monte Carlo modeling for
commodities that may be consumed in a single serving. These assessments
show that the MOE are significantly greater than the EPA standard of
100 for all subpopulations. The 95th percentile of exposure for the
overall U.S. population was estimated to be 0.000362 mg/kg/day (MOE of
2,762); 99th percentile 0.000732 mg/kg/day (MOE of 1,367); and 99.9th
percentile 0.002282 mg/kg/day (MOE of 438). The 95th percentile of
exposure for all infants < 1 year old was estimated to be 0.000652 mg/
kg/day (MOE of 1,534); 99th percentile 0.001138 mg/kg/day (MOE of 879);
and 99.9th percentile 0.001852 mg/kg/day (MOE of 540). The 95th
percentile of exposure for nursing infants < 1 year old was estimated
to be 0.000193 mg/kg/day (MOE of 5,180); 99th percentile 0.000456 mg/
kg/day (MOE of 2,192); and 99.9th percentile 0.000475 mg/kg/day (MOE of
2,107). The 95th percentile of exposure for non-nursing infants < 1
year old was estimated to be 0.000766 mg/kg/day (MOE of 1,306 ); 99th
percentile 0.001203 mg/kg/day (MOE of 832); and 99.9th percentile
0.001977 mg/kg/day (MOE of 506). The 95th percentile of exposure for
children 1 to 6 years old (the most highly exposed population subgroup)
was estimated to be 0.000632 mg/kg/day (MOE of 1,583); 99th percentile
0.001196 mg/kg/day (MOE of 836); and 99.9th percentile 0.005277 mg/kg/
day (MOE of 190). Therefore, FMC concludes that the acute dietary risk
of bifenthrin, as estimated by the dietary risk assessment, does not
appear to be of concern.
    ii. Chronic exposure and risk. The acceptable RfD is based on a
NOEL of 1.5 mg/kg/day from the chronic dog study and an uncertainty
factor of 100 is 0.015 mg/kg/day. The endpoint effect of concern were
tremors in both sexes of dogs at the LEL of 3.0 mg/kg/day. A chronic
dietary exposure/risk assessment has been performed for bifenthrin
using the above RfD. Available information on anticipated residues,
monitoring data, and percent crop treated was incorporated into the
analysis to estimate the anticipated residue contribution (ARC). The
ARC is generally considered a more realistic estimate than an estimate
based on tolerance level residues. The ARC are estimated to be 0.00002
mg/kg body weight (bwt)/day and utilize 0.1% of the RfD for the overall
U.S. population. The ARC for non-nursing infants (< 1 year) and
children 1-6 years old (subgroups most highly exposed) are estimated to
be 0.000042 mg/kg bwt/day and 0.000032 mg/kg bwt/day and utilizes 0.3%
and 0.2% of the RfD, respectively. Generally speaking, the EPA has no
cause for concern if the total dietary exposure from residues for uses
for which there are published and proposed tolerances is less than 100%
of the RfD. Therefore, FMC concludes that the chronic dietary risk of
bifenthrin, as estimated by the dietary risk assessment, does not
appear to be of concern.
    2. Drinking water. Laboratory and field data have demonstrated that
bifenthrin is immobile in soil and will not leach into groundwater.
Other data show that bifenthrin is virtually insoluble in water and
extremely lipophilic. As a result, FMC concludes that residues reaching
surface waters from field runoff will quickly adsorb to sediment
particles and be partitioned from the water column. Further, a
screening evaluation of leaching potential of a typical pyrethroid was
conducted using EPA's Pesticide Root Zone Model (PRZM3). Based on this
screening assessment, the potential concentrations of a pyrethroid in
groundwater 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
normally be treated before consumption. Based on these analyses, the
contribution of water to the dietary risk estimate is negligible.
Therefore, FMC concludes that together these data indicate that
residues are not expected to occur in drinking water.
    3. Non-dietary exposure. Analyses were conducted which included an
evaluation of potential non-dietary (residential) applicator, post-
application and chronic dietary aggregate exposures associated with
bifenthrin products used for residential flea infestation control and
agricultural/commercial applications. The aggregate analysis
conservatively assumes that a person is concurrently exposed to the
same active ingredient via the use of consumer or professional flea
infestation control products and to chronic level residues in the diet.
In the case of potential non-dietary health risks, conservative point
estimates of non-dietary exposures, expressed as total systemic
absorbed dose (summed across inhalation and incidental ingestion
routes) for each relevant product use category (i.e., lawn care) and
receptor subpopulation (i.e., adults, children 1-6 years and infants <
1 year) are compared to the systemic

[[Page 50354]]

absorbed dose NOEL for bifenthrin to provide estimates of the MOEs.
Based on the toxicity endpoints selected by EPA for bifenthrin,
inhalation and incidental oral ingestion absorbed doses were combined
and compared to the relevant systemic NOEL for estimating MOEs. In the
case of potential aggregate health risks, the above-mentioned
conservative point estimates of inhalation and incidental ingestion
non-dietary exposure (expressed as systemic absorbed dose) are combined
with estimates (arithmetic mean values) of chronic average dietary
(oral) absorbed doses. These aggregate absorbed dose estimates are also
provided for adults, children 1-6 years and infants < 1 year. The
combined or aggregated absorbed dose estimates (summed across non-
dietary and chronic dietary) are then compared with the systemic
absorbed dose NOEL to provide estimates of aggregate MOEs. The non-
dietary and aggregate (non-dietary + chronic dietary) MOEs for
bifenthrin indicate a substantial degree of safety. The total non-
dietary (inhalation + incidental ingestion) MOEs for post-application
exposure for the lawn care product evaluated was estimated to be >
51,000 for adults, 1,900 for children 1-6 years old and 1,800 for
infants < 1 year. The aggregate MOE (inhalation + incidental oral +
chronic dietary, summed across all product use categories) was
estimated to be 25,000 for adults, 1,800 for children 1-6 years old and
1,600 for infants (< 1 year). It can be concluded that the potential
non-dietary and aggregate (non-dietary + chronic dietary) exposures for
bifenthrin are associated with substantial margins of safety.

D. Cumulative Effects

    In consideration of potential cumulative effects of bifenthrin and
other substances that may have a common mechanism of toxicity, to our
knowledge there are currently no available data or other reliable
information indicating that any toxic effects produced by bifenthrin
would be cumulative with those of other chemical compounds; thus only
the potential risks of bifenthrin have been considered in this
assessment of its aggregate exposure. FMC intends to submit information
for the EPA to consider concerning potential cumulative effects of
bifenthrin consistent with the schedule established by EPA in the
Federal Register of August 4, 1997 (62 FR 42020) (FRL-5734-6), and
other EPA publications pursuant to the FQPA.

E. Safety Determination

    1. U.S. population. Based on a complete and reliable toxicology
data base, the acceptable reference dose (RfD) is 0.015 mg/kg/day,
based on a NOEL of 1.5 mg/kg/day from the chronic dog study and an
uncertainty factor of 100. Available information on anticipated
residues, monitoring data and percent crop treated was incorporated
into an analysis to estimate the Anticipated Residue Contribution (ARC)
for 26 population subgroups. The ARC is generally considered a more
realistic estimate than an estimate based on tolerance level residues.
The ARC are estimated to be 0.00002 mg/kg body weight (bwt)/day and
utilize 0.1% of the RfD for the overall U.S. population. The ARC for
non-nursing infants (< 1 year) and children 1-6 years old (subgroups
most highly exposed) are estimated to be 0.000042 mg/kg bwt/day and
0.000032 mg/kg bwt/day and utilizes 0.3% and 0.2% of the RfD,
respectively. Generally speaking, the EPA has no cause for concern if
the total dietary exposure from residues for uses for which there are
published and proposed tolerances is less than 100% of the RfD.
Therefore, FMC concludes that the chronic dietary risk of bifenthrin,
as estimated by the aggregate risk assessment, does not appear to be of
concern. For the overall U.S. population, the calculated MOE at the
95th percentile was estimated to be 2,762; 1,367 at the 99th
percentile; and 438 at the 99.9th percentile. For all infants < 1 year
old, the calculated MOE at the 95th percentile was estimated to be
1,534; 879 at the 99th percentile; and 540 at the 99.9th percentile.
For nursing infants < 1 year old, the calculated MOE at the 95th
percentile was estimated to be 5,180; 2,192 at the 99th percentile; and
2,107 at the 99.9th percentile. For non-nursing infants < 1 year old,
the calculated MOE at the 95th percentile was estimated to be 1,306;
832 at the 99th percentile; and 506 at the 99.9th percentile. For the
most highly exposed population subgroup, children 1-6 years old, the
calculated MOE at the 95th percentile was estimated to be 1,583; 836 at
the 99th percentile; and 190 at the 99.9th percentile. Therefore, FMC
concludes that there is reasonable certainty that no harm will result
from acute exposure to bifenthrin.
    2. Infants and children-- a. General. In assessing the potential
for additional sensitivity of infants and children to residues of
bifenthrin, FMC considered data from developmental toxicity studies in
the rat and rabbit, and a two-generation reproductive study in the rat.
The developmental toxicity studies are designed to evaluate adverse
effects on the developing organism resulting from pesticide exposure
during prenatal development to one or both parents. Reproduction
studies provide information relating to effects from exposure to the
pesticide on the reproductive capability of mating animals and data on
systemic toxicity. FFDCA section 408 provides that EPA may apply an
additional margin of safety for infants and children in the case of
threshold effects to account for pre- and post-natal toxicity and the
completeness of the data base.
    b. Developmental toxicity studies. In the rabbit developmental
study, there were no developmental effects observed in the fetuses
exposed to bifenthrin. The maternal NOEL was 2.67 mg/kg/day based on
head and forelimb twitching at the LOEL of 4 mg/kg/day. In the rat
developmental study, the maternal NOEL was 1 mg/kg/day, based on
tremors at the LOEL of 2 mg/kg/day. The developmental (pup) NOEL was
also 1 mg/kg/day, based upon increased incidence of hydroureter at the
LOEL 2 mg/kg/day. There were 5/23 (22%) litters affected (5/141 fetuses
since each litter only had one affected fetus) in the 2 mg/kg/day
group, compared with zero in the control, 1, and 0.5 mg/kg/day groups.
According to recent historical data (1992-1994) for this strain of rat,
incidence of distended ureter averaged 11% with a maximum incidence of
90%.
    c. Reproductive toxicity study. In the rat reproduction study,
parental toxicity occurred as decreased body weight at 5.0 mg/kg/day
with a NOEL of 3.0 mg/kg/day. There were no developmental (pup) or
reproductive effects up to 5.0 mg/kg/day (highest dose tested).
    d. Pre- and post-natal sensitivity-- i. Pre-natal. Since there was
not a dose-related finding of hydroureter in the rat developmental
study and in the presence of similar incidences in the recent
historical control data, the marginal finding of hydroureter in rat
fetuses at 2 mg/kg/day (in the presence of maternal toxicity) is not
considered a significant developmental finding. Nor does it provide
sufficient evidence of a special dietary risk (either acute or chronic)
for infants and children which would require an additional safety
factor.
    ii. Post-natal. Based on the absence of pup toxicity up to dose
levels which produced toxicity in the parental animals, there is no
evidence of special post-natal sensitivity to infants and children in
the rat reproduction study.
    e. Conclusion. Based on the above, FMC concludes that reliable data
support use of the standard 100-fold uncertainty factor, and that an
additional uncertainty factor is not needed to protect the safety of
infants

[[Page 50355]]

and children. As stated above, aggregate exposure assessments utilized
significantly less than 1% of the RfD for either the entire U.S.
population or any of the 26 population subgroups including infants and
children. Therefore, it may be concluded that there is reasonable
certainty that no harm will result to infants and children from
aggregate exposure to bifenthrin residues.

F. International Tolerances

    There are no Codex, Canadian, or Mexican residue limits for
residues of bifenthrin in or on cotton; corn, field, seed, pop;
strawberries; or hops. (Adam Heyward)

...

9. Zeneca Ag Products

PP 7G3518, 7F3521, 4F4406

    EPA has received a request from Zeneca Ag Products, P. O. Box
15458, Wilmington, DE, 19850-5458 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 by removing the time limitation for tolerances
established for residues of the insecticide and pyrethriod Tefluthrin
in or on the raw agricultural commodities corn, grain, field and pop;
corn, forage and fodder, field, pop and sweet; and corn, fresh
(including sweet K and corn with huskremoved (CWHR)) at 0.06 ppm. The
International Union of Pure and Applied Chemist (IUPAC) name for
tefluthrin is (2,3,5,6-tetrafluro-4-methylphenyl)methyl-(1 alpha, 3
alpha)-(Z)-(+/-)-3(2-chloro-3,3,3-trifluoro-1-propenyl)-2,2-
dimethylcyclopropanecarboxylate) and its metabolite (Z)-3-(2-chloro-
3,3,3-trifluroro-1-propenyl)-2,2-dimethylcyclopropanecarboxylic acid.
The tolerances were originally requested in Pesticide Petition Numbers
7G3518, 7F3521, and 4F4406. 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 nature of tefluthrin residues in plants
and animals for corn use is adequately understood. The residue of
concern is tefluthrin and its metabolite. There is no reasonable
expectation of secondary residues in animal tissues and milk from the
use as delineated in 40 CFR 180.6(a)(3).
    2. Analytical method. An adequate analytical method, gas liquid
chromatography with an electron capture detector, is available for
enforcement purposes. The enforcement methodology has been submitted to
the Food and Drug Administration, and is published in the Pesticide
Analytical Manual Vol. II (PAM II).
    3. Magnitude of residues. Tefluthrin (also know as FORCE
Insecticide) is an effective granular soil insecticide registered for
use against a number of soil corn pest; the most economically
significant being soil dwelling pest, such as corn rootworm, wireworm,
cutworm, and white grubs. Residue data covering all the uses associated
with the permanent tolerances requested by this petition have been
previously submitted to EPA for review and have been found by EPA to
support the requested tolerances. See February 1, 1989 (54 FR 5080);
and May 3, 1996 (61 FR 19852) (FRL-5358-5).

B. Toxicological Profile

    1. Acute toxicity. Acute toxicity studies with the technical grade
of the active ingredient tefluthrin: Oral LD50 in the rat is
22 mg/kg) for (males) and 35 mg/kg for (females); dermal
LD50 in the rat is 316 mg/kg in (males) and 177 mg/kg in
(females); acute inhalation LC50 in the rat is 0.04
milligram/liter (mg/l) and 0.05 mg/l in female and male rats,
respectively; primary eye irritation in the rabbit study showed slight
irritation; primary dermal irritation in the rabbit study showed none
to slight irritation, and the dermal sensitization in the guinea pig
study showed no skin sensitization.
    2. Genotoxicty. The following genotoxicity test were all negative:
A gene mutation assay (Ames), dominant lethal (mouse in vivo), mouse
micronucleus (in vivo), acute cytogenetic study in the rat, unscheduled
DNA synthesis and a mouse lymphoma cells test.
    3. Reproductive and developmental toxicity. In a rat developmental
study,

[[Page 50363]]

delayed ossification was noted in the highest dose group (5 mg/kg/day),
along with significant maternal toxicity (decreased body weight (bwt)).
The developmental no observed effect level (NOEL) for this study was
established at 3 mg/kg/day. However, the effects observed were most
likely a secondary effect resulting from maternal stress.
    In a developmental toxicity study in rabbits given gavage doses of
0, 3, 6, and 12 mg/kg/day, the maternal NOEL is 3 mg/kg/day and the
developmental NOEL is > 12 mg/kg/day. No developmental effects were
observed under the conditions of the study.
    In a rat multi-generation reproduction study, conducted at 0, 15,
50, and 250 ppm with tefluthrin in the diet, a reproductive NOEL was
established at 50 ppm (3.4 mg/kg/day) based on reduced pup weight and
litter size observed at 250 ppm (12.5 mg/kg/day). Parental toxicity (in
the form of abnormal, sprayed, or high-stepping gait) was also observed
at 250 ppm. Thus, the effects observed in offspring at 250 ppm is
considered to be secondary to maternal toxicity.
    4. Subchronic toxicity. A 90-day feeding study in which rats were
fed doses of 0, 50, 150, and 350 ppm with a NOEL of 50 ppm and a lowest
observed effect level (LOEL) of 150 ppm based on mild dose changes in
hemoglobin, cholesterol, and liver weight.
    A 90-day feeding study in which dogs were fed doses of 0, 0.1, 0.5,
and 1.5 mg/kg with a NOEL of 0.5 mg/kg and a LOEL of 1.5 mg/kg based on
increased triglycerides and AST.
    A 21-day dermal study in which rats were exposed dermally to doses
of 1, 5, and 50 mg/kg/day, 6 hours/day with a toxicological NOEL of
1mg/kg.
    5. Chronic toxicity. A 12-month feeding study in dogs was conducted
with a NOEL of 0.5 mg/kg/day. The LOEL for this study is established at
2 mg/kg/day based upon ataxia.
    A 24-month rat and mouse chronic feeding/oncogenicity studies were
conducted with systemic NOEL's of 1.1mg/kg/day and 3.4 mg/kg/day with
no oncogenic effects observed at dose levels up to and including 18.2
mg/kg/day and 54.4 mg/kg/day, the highest dose levels tested for rats
and mice, respectively.
    6. Animal metabolism. A metabolism study in the rat demonstrated
that distribution patterns and excretion rates in multiple oral dosing
periods are similar to single-dose studies. The metabolism of
tefluthrin in livestock has been studied in the goat and chicken. The
nature of tefluthrin residue in animals for corn use is adequately
understood. The residue of concern is tefluthrin and its metabolite.
There is no reasonable expectation of secondary residues in animal
tissues and milk from the use as delineated in 40 CFR 180.6(a)(3).
    7. Metabolite toxicology. The nature of tefluthrin residue in
plants and animals for corn use is adequately understood. The residue
of concern is tefluthrin and its metabolite. There is no reasonable
expectation of secondary residues in animal tissues and milk from the
use as delineated in 40 CFR 180.6(a)(3). An adequate analytical method,
gas liquid chromatography with an electron capture detector, is
available for enforcement purposes. The enforcement methodology has
been submitted to the Food and Drug Administration, and is published in
the Pesticide Analytical Manual Vol. II (PAM II).
    8. Endocrine disruption. EPA is required to develop a screening
program to determine whether certain substances (including all
pesticides and inerts) ``may have an effect produced by a naturally
occurring estrogen, or such other endocrine effect... .'' The Agency is
currently working with interested stakeholders, including other
government agencies, public interest groups, industry and research
scientists, in developing a screening and testing program and a
priority setting scheme to implement this program. Congress has allowed
3 years from passage of the Food Quality Protection Act (FQPA) (August
3, 1999) to implement this program. At that time, EPA may require
further testing of this active ingredient and end use products for
endocrine disrupter effects.

C. Aggregate Exposure

    The primary source of human exposure to tefluthrin will be from
ingestion of raw and processed food commodities which have been treated
with tefluthrin. These commodities include corn, grain, field and pop;
corn, forage and fodder, field, pop and sweet; and corn, fresh
(including sweet K and CWHR) as listed in 40 CFR 180.440. There is no
reasonable expectation of secondary residues in animal tissues, milk,
or eggs from use as delineated in 40 CFR 180.6(a)(3).
    1. Dietary exposure. For purposes of assessing the potential
dietary exposure under these tolerances, aggregate exposure is
estimated based on the Theoretical Maximum Residue Contribution (TMRC)
from the existing tolerances for tefluthrin in food crops. The TMRC is
obtained by multiplying the tolerance level residues by the consumption
data which estimates the amount of those food products eaten by various
population subgroups. The following assumptions were used in conducting
this exposure assessment: 100 percent of the crops were treated, and
the raw agricultural commodities (RAC) residues would be at the level
of the tolerance. This results in an overestimate of human exposure and
a conservative assessment of risk.
    2. Food. The acute dietary risk assessment used tolerance level
residues and assumed that 100 percent of all crops were treated. Thus,
this acute dietary exposure estimate is considered ``worst-case'' and
severely overestimates potential exposure. The acute dietary Margin of
Exposure (MOE) for the most highly exposed population subgroup was
children ages one to six. The MOE's were 2,436 at the 95th percentile,
1,342 at the 99th percentile, and 738 at the 99.9th percentile. EPA
concludes that there is a reasonable certainty of no harm for MOE of
100 or greater. Therefore, the acute dietary risk assessment for
tefluthrin clearly indicates a reasonable certainty of no harm.
    For the chronic dietary assessment Zeneca used the standard EPA
conservative exposure assumptions (i.e. tolerance level residues and
100 percent market share), and based on the completeness and
reliability of the toxicity data Zeneca has concluded that the
aggregate exposure to this chemical will utilize less than one percent
(0.40 percent) of the reference dose (RfD) for the U. S. population.
The most highly exposed population subgroup was children ages one to
six with a total dietary exposure of 0.000049 mg/kg bwt/day (1.0
percent of the RfD). Since EPA generally has no concern for exposures
below 100 percent of the RfD, there is a reasonable certainty that no
harm will result from aggregate exposure to residues.
    3. Drinking water. Tefluthrin is immobile in soil and, therefore,
will not leach into ground water. Additionally, due to the insolubility
and lipophilic nature of tefluthrin, 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 synthetic
pyrethroid was conducted using EPA's Pesticide Root Zone Model (PRZM3).
Based on this screening assessment, potential concentrations of a
pyrethroid in ground water at depths of 1 to 2 meters are essentially
zero (<0.001 ppb). Surface water concentrations for pyrethroids were
estimated using PRZM3 and Exposure Analysis

[[Page 50364]]

Modeling Systems (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 normally be treated before consumption. Based on
these analyses, the contribution of water to the dietary risk estimate
is negligible.
    4. Non-dietary exposure. The potential for non-occupational
exposure to the general population is expected to be essentially zero.
Tefluthrin is not registered for aquatic and/or domestic outdoor or
indoor uses. The major use (corn) is applied only once per year at
planting as a granular formulation. The other use is limited to
commercial seed treatment of field corn, popcorn, seedcorn, and sweet
corn seed. There is a commercial use in liquid slurry seed treaters and
seed coating equipment, which is not for use on agricultural
establishments in hopper-box, planter-box, slurry-box, or other seed
treatment applications. The other minor use is for the treatment of
fire ants for containerized and balled nursery stock under the USDA/
APHIS Imported Fire Ant Quarantine Program (Department of Agriculture-
Animal and Plant Health Inspection Service-7 CFR part 301).

D. Cumulative Effects

    Zeneca will submit information for EPA to consider concerning
potential cumulative effects of tefluthrin consistent with the schedule
established by EPA on August 4, 1997 (62 FR 42020) (FRL-5734-6) and
other EPA publications pursuant to the FQPA. At this time, Zeneca
cannot make a determination, based on available and reliable
information, that tefluthrin and other substances that may have a
common mechanism of toxicity would have cumulative effects. Therefore,
for purposes of this request it is appropriate only to consider the
potential risks of tefluthrin in an aggregate exposure assessment.

E. Safety Determination

    1. U.S. population. EPA recently reviewed all of the toxicity end
points for the synthetic pyrethroids. Based on this review EPA
concluded that the chronic RfD is 0.005 mg/kg/day. This RfD is based on
a 1-year dog feeding study with a NOEL of 0.5 mg/kg/day for ataxia, and
a 100-fold uncertainty factor. In addition, EPA derived an acute NOEL
of 0.5 mg/kg/day for use in acute dietary risk assessment. This NOEL is
based on the 1-year dog feeding study in which increased incidence of
tremors in both sexes of dogs was observed on the first day of dosing.
    Using these RfD's and EPA's standard default assumptions (i.e.
tolerance level residues and 100 percent market share), Zeneca assessed
the potential acute and chronic dietary risk to the general U.S.
population and 22 subpopulations. These analyses are considered
``worst-case'', and the results concluded that for the U.S. population,
uses were 0.000021 mg/kg/day (0.4 of the RfD). The acute MOE's at the
95th, 99th, and 99.9th percentile were 5.195, 2,449, and 1,091
respectively. The most highly exposed population subgroup (children
ages one to six), utilizes 1.0 percent of the chronic RfD, and the
acute dietary MOE's at the 95th, 99th, and 99.9th percentiles were
2,436, 1,342, and 738, respectively. These assessments indicate a
reasonable certainty that no harm will result from aggregate exposure
to residues.
    2. Infants and children. Section 408 of the FFDCA provides that EPA
shall apply an additional 10-fold margin of safety for infants and
children in the case of threshold effects to account for pre- and post-
natal toxicity and the completeness of the database unless EPA
determines that a different margin of safety will be safe for infants
and children. EPA generally defines the level of appreciable risk as
exposure that is greater than \1/100\ of the NOEL in the animal study
appropriate to the particular risk assessment. This 100-fold
uncertainty (safety) factor/margin of exposure is designed to account
for combined inter- and intra-species variability. EPA believes that
reliable data support using the standard 100-fold margin/factor, not
the additional 10-fold margin/factor, when EPA has a complete database
under existing guidelines and when the severity of the effect in
infants and children or the potency or unusual toxic properties of a
compound do not raise concerns regarding the adequacy of the standard
margin/factor.
    In assessing the potential for additional sensitivity of infants
and children to residues of tefluthrin, EPA considered the data from
oral developmental toxicity studies in the rat and rabbit, as well as
data from a multi-generation reproduction study in the rat. The
developmental toxicity studies are designed to evaluate adverse effects
in the developing organism resulting from pesticide exposure during
prenatal development in the mothers. Reproduction studies provide
information relating to effects from exposure to the pesticide on the
reproductive capability of mating animals and data on systemic
toxicity.
    3. Pre-natal effects. In a rat developmental study delayed
ossification was noted in the highest dose group (5 mg/kg/day), along
with significant maternal toxicity (decreased bwt). The developmental
NOEL for this study was established at 3 mg/kg/day. However, the
effects observed were most likely a secondary effect resulting from
maternal stress.
    In a developmental toxicity study in rabbits given gavage doses of
0, 3, 6, and 12 mg/kg/day the maternal NOEL is 3 mg/kg/day, and the
developmental NOEL is > 12 mg/kg/day. No developmental effects were
observed under the conditions of the study.
    4. Post-natal effects. In a rat multi-generation reproduction study
conducted at 0, 15, 50, and 250 ppm with tefluthrin in the diet, a
reproductive NOEL was established at 50 ppm (3.4 mg/kg/day), based on
reduced pup weight and litter size observed at 250 ppm (12.5 mg/kg/
day). Parental toxicity (in the form of abnormal, sprayed, or high-
stepping gait) was also observed at 250 ppm. Thus, the effects observed
in offspring at 250 ppm is considered to be secondary to maternal
toxicity.
    In EPA's review of the toxicity endpoints for tefluthrin they
concluded that the data on developmental and reproductive toxicity
tests do not indicate any increased pre- or post-natal sensitivity.
Therefore, EPA concluded that reliable data support use of a 100-fold
safety factor, and additional 10-fold safety factor is not needed. This
aggregate assessment of tefluthrin clearly demonstrates that there is
no harm for all population groups.

F. International Tolerances

    There are no Codex Maximum Residue Levels (MRL's) established for
tefluthrin. (John Hebert)

10. Zeneca Ag Products

PPs 7F3560, 7H5543, 7F3488, 1F3952, 1H5607, 1F3992, 2F4109, 2F4100,
2F4114, 1F3985, and 6F4769

    EPA has received a request from Zeneca Ag Products, 1800 Concord
Pike, P.O. Box 15458, Wilmington, Delaware 19850-5458, 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 180.438 by removing the
time limitation for tolerances established for residues of lambda-
cyhalothrin and its epimer in or on the following crops and
commodities: broccoli at 0.4 ppm;

[[Page 50365]]

cabbage at 0.4 ppm; cattle, fat at 3.0 ppm; cattle, meat at 0.2 ppm;
cattle, meat and meat by-products (mbyp) at 0.2 ppm; corn, grain (field
and pop) at 0.05 ppm; corn, fodder at 1.0 ppm; corn, forage at 6.0 ppm;
corn, sweet (k+kwhr) at 0.05 ppm; cottonseed at 0.05 ppm; dry bulb
onion at 0.1 ppm; eggs at 0.01 ppm; garlic at 0.1 ppm; goats, fat at
3.0 ppm; goats, meat at 0.2 ppm; goats, mbyp at 0.2 ppm, hogs, fat at
3.0 ppm; hogs, meat at 0.2 ppm; hogs, mbyp at 0.2 ppm; horses, fat at
3.0 ppm; horses, meat at 0.2 ppm; horses, mbyp at 0.2 ppm; lettuce,
head at 2.0 ppm; milk, fat (reflecting 0.2 ppm in whole milk) at 5.0
ppm; peanuts at 0.05 ppm; peanuts, hulls at 0.05 ppm; poultry, fat at
0.01 ppm; poultry, meat at 0.01 ppm; poultry, mbyp at 0.01 ppm; rice,
grain at 1.0 ppm; rice, hulls at 5.0 ppm; rice, straw at 1.8 ppm;
sheep, fat at 3.0 ppm; sheep, meat at 0.2 ppm; sheep, mbyp at 0.2 ppm;
soybeans at 0.01 ppm; sorghum, grain at 0.02 ppm; sorghum, grain dust
at 1.5 ppm; sunflower, seeds at 0.2 ppm; sunflower, forage at 0.2 ppm;
tomatoes at 0.1 ppm; wheat, grain at 0.05 ppm; wheat, forage at 2.0
ppm; wheat, hay at 2.0 ppm; wheat, straw at 2.0 ppm; wheat, grain dust
at 2.0 ppm; corn, grain flour at 0.15 ppm; sunflower, oil at 0.30 ppm;
sunflower, hulls at 0.50 ppm; tomato pomace (dry or wet) at 6.0 ppm;
and wheat, bran at 0.2 ppm. The IUPAC name for lambda-cyhalothrin is a
1:1 mixture of (S)-alpha-cyano-3-phenoxybenzyl-(Z)-(1R,3R)-3-(2-chloro-
3,3,3-trifluoroprop-1-enyl)-2,2-dimethylcyclopropanecarboxylate and
(R)-alpha-cyano-3-phenoxybenzyl-(Z)-(1S,3S)-3-(2-chloro-3,3,3-
trifluoroprop-1-enyl)-2,2-dimethylcyclopropanecarboxylate and the
epimer of lambda-cyhalothrin is a 1:1 mixture of (S)-alpha-cyano-3-
phenoxybenzyl-(Z)-(1S,3S)-3-(2-chloro-3,3,3-trifluoroprop-1-enyl)-2,2-
dimethylcyclopropanecarboxylate and (R)-alpha-cyano-3-phenoxybenzyl-
(Z)-(1R,3R)-3-(2-chloro-3,3,3-trifluoroprop-1-enyl)-2,2-
dimethylcyclopropanecarboxylate. These tolerances were originally
requested in Pesticide Petition Numbers 7F3560, 7H5543, 7F3488, 1F3952,
1H5607, 1F3992, 2F4109, 2F4100, 2F4114, 1F3985, and 6F4769. EPA has
determined that the petitions 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 the request. Additional data
may be needed before EPA rules on the request.

A. Residue Chemistry

    1. Plant metabolism.The metabolism of lambda-cyhalothrin has been
studied in cotton, soybean, cabbage and wheat plants. The studies show
that the metabolism generally follows that of other pyrethroid
insecticides. The ester linkage is cleaved to form
cyclopropanecarboxylic acids and the corresponding phenoxybenzyl
alcohol. Overall the studies show that unchanged lambda-cyhalothrin is
the principal constituent of the residue on edible portions of these
crops.
    2. Analytical method. An adequate analytical method (gas liquid
chromatography with an electron capture detector) is available for
enforcement purposes.
    3. Magnitude of residues. Field residue trials, meeting EPA study
requirements, have been conducted for each crop in this petition. These
data have previously been reviewed and classified by the Agency as
supportive of these tolerances.

B. Toxicological Profile

    The following toxicity studies have been conducted to support this
request.
    1. Acute toxicity. Acute toxicity studies with the technical grade
of the active ingredient lambda-cyahothrin: oral LD50 in the
rat of 79 millgrams/kilogram (mg/kg) (males) and 56 mg/kg (females),
dermal LD50 in the rat of 632 mg/kg (males) and 696 mg/kg
females, primary eye irritation study showed mild irritation and
primary dermal irritation study showed no irritation.
    2. Genotoxicty. The following genotoxicity tests were all negative:
a gene mutation assay (Ames), a mouse micronucleus assay, an in-vitro
cytogenetics assay, and a gene mutation study in mouse lymphoma cells.
    3. Reproductive and developmental toxicity. A three-generation
reproduction study in rats fed diets containing 0, 10, 30, and 100 ppm
with no developmental toxicity observed at 100 ppm, the highest dose
tested. The maternal NOEL and LOEL for the study are established at 30
(1.5 mg/kg/day) and 100 ppm (5 mg/kg/day), respectively, based upon
decreased parental body weight gain. The reproductive NOEL and LOEL are
established at 30 (1.5 mg/kg/day) and 100 ppm (5 mg/kg/day),
respectively, based on decreased pup weight gain during weaning.
    A developmental toxicity study was conducted in rats given gavage
doses of 0, 5, 10, and 15 mg/kg/day with no developmental toxicity
observed under the conditions of the study. The developmental NOEL is
greater than 15 mg/kg/day, the highest dose tested. The maternal NOEL
and LOEL are established at 10 and 15 mg/kg/day, respectively, based on
reduced body weight gain.
    A developmental toxicity study was conducted in rabbits given
gavage doses of 0, 3, 10, and 30 mg/kg/day with no developmental
toxicity observed under the conditions of the study. The maternal NOEL
and LOEL are established at 10 and 30 mg/kg/day, respectively based on
decreased body weight gain. The developmental NOEL is greater than 30
mg/kg/day, the highest dose tested.
    4. Subchronic toxicity. A 90-day feeding study in rats fed doses of
0, 10, 50 and 250 ppm with a NOEL of 50 ppm and a LOEL of 250 ppm based
on body weight gain reduction.
    A study where lambda-cyhalothrin in olive oil was applied to the
skin of rats for 21 successive days at dose rates of 1, 10, or 100
(reduced to 50 after 2-3 applications) mg/kg/day. A NOEL of 10 mg/kg/
day is based on clinical signs of slight general toxicity at 50 mg/kg/
day.
    5. Chronic toxicity. A 12-month feeding study was conducted in dogs
fed dose (by capsule) levels of 0, 0.1, 0.5, 3.5 mg/kg/day with a NOEL
of 0.1 mg/kg/day. The LOEL for this study is established at 0.5 mg/kg/
day based upon clinical signs of neurotoxicity.
    A 24-month chronic feeding/carcinogenicity study was conducted with
rats fed diets containing 0, 10, 50, and 250 ppm. The NOEL was
established at 50 ppm and LOEL at 250 ppm based on reduced body weight
gain. There were no carcinogenic effects observed under the conditions
of the study.
    A carcinogenicity study was conducted in mice fed dose levels of 0,
20, 100, or 500 ppm (0, 3, 15, or 75 mg/kg/day) in the diet for 2
years. A systemic NOEL was established at 100 ppm and systemic LOEL at
500 ppm based on decreased body weight gain in males throughout the
study at 500 ppm. The Agency has classified lambda-cyhalothrin as a
Group D carcinogen (not classifiable due to an equivocal finding in
this study). It is Zeneca's position that no treatment-related
carcinogenic effects were observed under the conditions of the study.
    6. Animal metabolism. Metabolism studies in rats demonstrated that
distribution patterns and excretion rates in multiple oral dose studies
are similar to single-dose studies. Accumulation of unchanged compound
in fat upon chronic administration shows slow elimination. Otherwise,
lambda-cyhalothrin was rapidly metabolized and excreted. The metabolism
of

[[Page 50366]]

lambda-cyhalothrin in livestock has been studied in the goat, chicken,
and cow. Unchanged lambda-cyhalothrin is the major residue component of
toxicological concern in meat and milk.
    Human metabolism of lambda-cyhalothrin was assessed by
administering 5 mg lambda-cyhalothrin orally to six male volunteers
(average dose was 0.06 mg/kg) and dermally at 20 mg/800 cm2
to five volunteers. No adverse effects were noted in the individuals
given an oral dose, and only mild signs of parasthesia were noted in
individuals receiving a dermal dose. Absorption by these two routes of
exposure were determined by analysis of urinary metabolites. An average
amount of 59% of the oral dose was absorbed. Dermal absorption was
extremely low, and estimated to be 0.12% (range 0.04-0.19%).
    7. Metabolite toxicology. The Agency has previously determined that
the metabolites of lambda-cyhalothrin are not of toxicological concern
and need not be included in the tolerance expression. Given this
determination, it is concluded that there is no need to discuss
metabolite toxicity.
    8.  Endocrine disruption. EPA is required to develop a screening
program to determine whether certain substances (including all
pesticides and inerts) ``may have an effect in humans that is similar
to an effect produced by a naturally occurring estrogen, or such other
endocrine effect***.'' The Agency is currently working with interested
stakeholders, including other government agencies, public interest
groups, industry and research scientists in developing a screening and
testing program and a priority setting scheme to implement this
program. Congress has allowed 3 years from the passage of FQPA (August
3, 1999) to implement this program. At that time, EPA may require
further testing of this active ingredient and end use products for
endocrine disrupter effects.

C. Aggregate Exposure

    Zeneca has conducted an aggregate exposure assessment for lambda-
cyhalothrin. This assessment included exposures resulting from
agricultural crop use and non-dietary residential use.
    1. Dietary exposure. For the purposes of assessing the potential
chronic dietary exposure for all existing and pending tolerances for
lambda-cyhalothrin, Zeneca has utilized available information on
anticipated residues (FDA monitoring data, average field trial residues
and processing data) and percent crop treated. For the acute dietary
assessment, a Monte Carlo modeling was used to estimate exposure.
    2. Food. The Agency has stated that the acute dietary risk
assessment for lambda-cyhalothrin should be based on a toxicological
NOEL from a 1-year dog study. Zeneca disagrees with EPA's selection of
a multiple-dose toxicological endpoint (0.5 mg/kg) for the acute
dietary risk assessment, and have requested the Agency to base the
acute dietary NOEL on single-dose effects. Acute risk, by EPA
definition, results from 1-day consumption of food and water, and
reflects toxicity which could be expressed following a single oral
exposure to pesticide residues. Therefore, an appropriate NOEL must be
based on effects noted after a single dose, even if the endpoint is
selected from a repeat dose study, such as a 1-year dog. Nonetheless,
sufficient margins of exposure are achieved at percentiles of exposure
up to and including the 99.9th percentile based on the Agency's NOEL of
0.5 mg/kg.
    Based on the Agency's selected acute toxicity endpoint of 0.5 mg/kg
bw day, the acute dietary MOE for the most highly exposed population
subgroup was children 1-6 years old. The MOEs were 658 at the 95th
percentile, 248 at the 99th percentile, and 132 at the 99.9th
percentile. EPA concludes that there is a reasonable certainty of no
harm for a MOE of 100 or greater. Therefore, the acute dietary risk
assessment for lambda-cyhalothrin clearly indicates a reasonable
certainty of no harm. The assessment of chronic dietary exposure was
estimated to be 5.0% of the chronic reference dose (RfD) for the
overall U.S. population. The RfD for lambda-cyhalothrin, 0.001 mg/kg bw
/day, is based on the NOEL of 0.1 mg/kg from the 1-year dog study and
an Uncertainty Factor of 100. For the most exposed subgroup, children
1-6 years old, the exposure was estimated to be 0.000159 mg/kg bw/day,
or 15.9% of the RfD. Since EPA generally has no concern for exposures
below 100 percent of the RfD, there is a reasonable certainty that no
harm will result from chronic dietary exposure to lambda-cyhalothrin
residues.
    3. Drinking water. Laboratory and field data have demonstrated that
lambda-cyhalothrin and its degradates are immobile in soil and will not
leach into ground water. Other data show that lambda-cyhalothrin is
virtually insoluble in water and extremely lipophilic. As a result,
residues reaching surface waters from field runoff will quickly adsorb
to sediment particles and be partitioned from the water column.
Together these data indicate that residues are not expected in drinking
water.
    A screening evaluation of leaching potential of a typical
pyrethroid was conducted using EPA's Pesticide Root Zone Model (PRZM3).
Based on this screening assessment, the potential concentrations of a
pyrethorid in ground water at depths of 1 and 2 meters are essentially
zero (< 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 normally be treated before consumption. Based on
these analyses, the contribution of water to the dietary risk estimate
is negligible.
    4. Non-dietary exposure. Other potential sources of exposure are
from non-occupational sources such as structural pest control and
ornamental plant and lawn use of lambda-cyhalothrin. In its review of
toxicity endpoints for assessing risks for lambda-cyhalothrin, the
Agency concluded that the most appropriate endpoint for non-dietary
risk assessment is 10 mg/kg bw/day based on the NOEL from the 21-day
dermal toxicity study. Exposure was estimated using available market
use information and surrogate indoor exposure data. The resulting MOEs
were 15,000 for the U.S. population, 7,000 for non-nursing infants and
7,200 for children 1-6 years old. The aggregate risk assessment of
combined exposures from chronic dietary, drinking water and non-dietary
residential sources has been conducted. The resulting MOEs are 14,000
for the U.S. Population, 6,500 for non-nursing infants and 6,500 for
children 1-6 years old. EPA concludes that there is a reasonable
certainty of no harm for MOE of 100 or greater. Therefore, the non-
dietary and overall aggregate risk assessments for lambda-cyhalothrin
clearly indicates a reasonable certainty of no harm.

D. Cumulative Effects

    Zeneca Ag Products will submit information for EPA to consider
concerning potential cumulative effects of lambda-cyhalothrin
consistent with the schedule established by EPA at 62 FR 42020 (August
4, 1997)(FRL-5734-6) and other EPA publications pursuant to the FQPA.
At this time, Zeneca cannot make a determination based on

[[Page 50367]]

available and reliable information that lambda-cyhalothrin and other
substances that may have a common mechanism of toxicity would have
cumulative effects. Therefore for purposes of this request it is
appropriate only to consider the potential risks of lambda-cyhalothrin
in an aggregate exposure assessment.

E. Safety Determination

    The acceptable RfD based on a NOEL of 0.1 mg/kg bw/day from the
chronic dog study and a safety factor of 100 is 0.001 mg/kg bw/day. A
chronic dietary exposure/risk assessment has been performed for lambda-
cyhalothrin using the above RfD. Available information on anticipated
residues, monitoring data and percent crop treated was incorporated
into the analysis to estimate the Anticipated Residue Contribution
(ARC). The ARC is generally considered a more realistic estimate than
an estimate based on tolerance level residues.
    1. U.S. population. The ARC from established tolerances and the
current and pending actions are estimated to be 0.00005 mg/kg bw/day
and utilize 5.0 per cent of the RfD for the U.S. population. For the
acute dietary assessment the MOEs at the 95th, 99th, and 99.9th
percentiles are 2074, 742, and 237, respectively.
    2. Infants and children. FFDCA section 408 provides that EPA shall
apply an additional tenfold margin of safety for infants and children
in the case of threshold effects to account for pre- and post-natal
toxicity and the completeness of the database unless EPA determines
that a different margin of safety will be safe for infants and
children. EPA generally defines the level of appreciable risk as
exposure that is greater than 1/100 of the NOEL in the animal study
appropriate to the particular risk assessment. This hundredfold
uncertainty (safety) factor/margin of exposure is designed to account
for combined inter and intraspecies variability. EPA believes that
reliable data support using the standard hundredfold margin/factor and
not the additional tenfold margin/factor when EPA has a complete
database under existing guidelines and when the severity of the effect
in infants and children or the potency or unusual toxic properties of a
compound do not raise concerns regarding the adequacy of the standard
margin/factor.
    In assessing the potential for additional sensitivity of infants
and children to residues of lambda-cyhalothrin, EPA considered the data
from oral developmental toxicity studies in the rat and rabbit, as well
as data from a multi-generation reproduction study in the rat. The
developmental toxicity studies are designed to evaluate adverse effects
in the developing organism resulting from pesticide exposure during
prenatal development in the mothers. Reproduction studies provide
information relating to effects from exposure to the pesticide on the
reproductive capability of mating animals and data on systemic
toxicity.
    i. Pre-natal effects. A developmental toxicity study in rats given
gavage doses of 0, 5, 10, and 15 mg/kg/day with no developmental
toxicity observed under the conditions of the study. The developmental
NOEL is greater than 15 mg/kg/day, the highest dose tested. The
maternal NOEL and LOEL are established at 10 and 15 mg/kg/day,
respectively, based on reduced body weight gain.
    A developmental toxicity study in rabbits given gavage doses of 0,
3, 10, and 30 mg/kg/day with no developmental toxicity observed under
the conditions of the study. The maternal NOEL and LOEL are established
at 10 and 30 mg/kg/day, respectively based on decreased body weight
gain. The developmental NOEL is greater than 30 mg/kg/day, the highest
dose tested.
    ii. Post-natal effects. A three-generation reproduction study in
rats fed diets containing 0, 10, 30, and 100 ppm with no developmental
toxicity observed at 100 ppm, the highest dose tested. The maternal
NOEL and LOEL for the study are established at 30 (1.5 mg/kg/day) and
100 ppm (5 mg/kg/day), respectively, based upon decreased parental body
weight gain. The reproductive NOEL and LOEL are established at 30 (1.5
mg/kg/day) and 100 ppm (5 mg/kg/day), respectively, based on decreased
pup weight gain during weaning.
    In EPA's review of the toxicity endpoints for lambda-cyhalothrin
they concluded that the data on developmental and reproductive toxicity
tests do not indicate any increased pre- or post-natal sensitivity.
Therefore, EPA concluded that reliable data support use of a
hundredfold safety factor and that an additional tenfold safety factor
is not needed.
    Based on this information the ARC for children 1-6 years old, and
non-nursing infants (subgroups most highly exposed) utilizes 0.000159
mg/kg bw/day (15.9% of the RfD) and 0.000101 mg/kg bw/day (10.1% of the
RfD), respectively. Generally speaking, the Agency has no cause for
concern if anticipated residues contribution for all published and
proposed tolerances is less than the RfD.
    For the acute dietary assessment the MOEs at the 95th, 99th, and
99.9th percentiles are 658, 248, and 132, respectively for children 1-6
years old. For non-nursing infants the MOEs at the 95th, 99th and
99.9th percentiles are 710, 316, and 152, respectively.

F. International Tolerances

     There are Codex maximum residue levels established for residues of
cyhalothrin, as the sum of all isomers, in or on the following crops
and commodities: pome fruits at 0.2 ppm; cabbage, head at 0.2 ppm;
potatoes at 0.02 ppm; cotton seed at 0.02 ppm; cotton seed oil, crude
at 0.02 ppm; and cotton seed oil, edible at 0.02 ppm. (Adam Heyward)

[FR Doc. 97-25499 Filed 9-22-97; 3:06 pm]
BILLING CODE 6560-50-F