[Federal Register Volume 62, Number 186 (Thursday, September 25, 1997)]
[Notices]
[Pages 50337-50367]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-25499]


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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-
[email protected]. 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: [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-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:
    [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 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.

1. AgrEvo USA Company

PP 2F4055, 6F3436, 4F2993, 6F3309

    EPA has received a request from AgrEvo USA Company (acting as 
registered US agent for Hoechst Schering AgrEvo, S. A., Little Falls 
Centre, 2711 Centerville Road,

[[Page 50338]]

Wilmington, DE 19808, 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 removing the time limitation for tolerances established for 
residues of the insecticides and pyrethroid Deltamethrin and 
Tralomethrin in or on the following raw agricultural commodities: 
Deltamethrin - cottonseed at 0.04 parts per million (ppm) and 
cottonseed oil at 0.2 ppm; and Tralomethrin - broccoli at 0.50 ppm, 
cottonseed at 0.02 ppm, lettuce, head at 1.00 ppm, lettuce, leaf at 
3.00 ppm, soybeans at 0.05 ppm, sunflower seed at 0.05 ppm and 
cottonseed oil at 0.20 ppm. The IUPAC name for deltamethrin is [(1R, 
3R)-3(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylic acid (S)-
alpha-cyano-3-phenoxybenzyl ester] and for tralomethrin is [(1R, 
3S)3[(1' RS)(1',2',2',2',-tetrabromo-ethyl)]-2,2-dimethylcyclopropane-
carboxylic acid (S)-alpha-cyano-3-phenoxybenzyl ester]. The tolerances 
were originally requested in Pesticide Petition Numbers 2F4055, 6F3436, 
4F2993, 6F3309. Based on the fact that tralomethrin is rapidly 
metabolized in plants and animals to deltamethrin, and the 
toxicological profile of the two compounds is similar, it is 
appropriate to consider combined exposure assessments for tralomethrin 
and deltamethrin. 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 permanent tolerance. Additional data may be needed before EPA rules 
on the petition.

A. Residue Chemistry

    1. Plant metabolism. Deltamethrin metabolism studies in tomatoes, 
corn, apples, and cotton demonstrate the same metabolic pathway. 
Furthermore, plant metabolism studies have been conducted following 
application of tralomethrin in cotton, corn, cabbage, and tomatoes. 
These studies have demonstrated that the metabolism of tralomethrin 
involves debromination to deltamethrin and its isomers. Thus, a similar 
metabolic pathway has been shown to occur in a variety of crops 
following either direct application of deltamethrin (cotton, corn, 
apples, and tomatoes) or in-plant formation of deltamethrin via 
debromination of applied tralomethrin (tomatoes, cotton, corn, and 
cabbage). As a result of this substantial information base, it is 
concluded that the residues of toxicological concern in/on growing 
crops following application of tralomethrin or deltamethrin are 
tralomethrin, cis-deltamethrin, and its isomers, trans-deltamethrin and 
alpha-R-deltamethrin.
    2. Analytical method. Analytical methods for determining residues 
of tralomethrin and deltamethrin in the commodities for which 
registrations have been approved, have been previously submitted to, 
and reviewed by, the Agency. These methods, based on gas 
nyhromatography (GLC) equipped with an electron capture detector (ECD) 
and a DB-1 (or equivalent) capillary column, are used for the 
determination of tralomethrin, cis-deltamethrin, trans-deltamethrin, 
and alpha-R-deltamethrin in various raw agricultural, animal derived, 
and processed commodities. These methods were independently validated 
and are appropriate for the determination of residues of tralomethrin 
and deltamethrin in various food and feed commodities after application 
of these ingredients to target growing crops, and after use in food/
feed handling establishments.
    3. Magnitude of residues. Residues of tralomethrin, deltamethrin, 
and its metabolites are not expected to exceed the established 
tolerance levels as a result of the use of these active ingredients on 
target crops.

B. Toxicological Profile

    1. Acute toxicity. The acute oral LD50 values for 
deltamethrin in the rat are 66.7 mg/kg for males, 86 mg/kg for females 
and for tralomethrin 99 mg/kg for males, 157 mg/kg for females when 
administered in sesame oil. The oral LD50 for deltamethrin 
when administered in aqueous methyl cellulose was greater than 5,000 
mg/kg for both sexes. The dermal LD50 in rabbits was greater 
than 2,000 mg/kg for both materials. Inhalation 4-hour LC50 
values in the rat are 2.2 mg/L for deltamethrin and greater than 0.286 
mg/L for tralomethrin.
    2. Genotoxicity. No indication of genotoxicity was noted in a 
battery of in vivo and in vitro studies conducted with either 
deltamethrin or tralomethrin.
    3. Reproductive and developmental toxicity-- a. Deltamethrin A rat 
developmental toxicity study conducted with deltamethrin indicated a 
maternal no-observed-effect levels (NOEL) of 3.3 mg/kg/day based on 
clinical observations, decreased weight gain and mortality. The 
developmental NOEL was 11 mg/kg/day [highest dose tested] (HDT). In a 
rabbit developmental toxicity study with deltamethrin, the maternal 
NOEL was considered to be 10 mg/kg/day based on decreased defecation at 
25 and 100 mg/kg/day, and mortality at 100 mg/kg/day. The developmental 
NOEL was considered to be 25 mg/kg/day based on retarded ossification 
of the pubic and tail bones at 100 mg/kg (HDT). A three-generation rat 
reproduction study and a more recent, two-generation rat reproduction 
study with deltamethrin indicated the NOEL for both parents and 
offspring was 80 ppm (4-12 mg/kg/day for adults and 18-44 mg/kg/day for 
offspring) based on clinical signs of toxicity, reduced weight gain and 
mortality at 320 ppm (HDT).
    b. Tralomethrin. In a rat developmental toxicity study with 
tralomethrin the NOEL for maternal and developmental toxicity was 
judged to be greater than or equal to 18 mg/kg/day (HDT). No evidence 
of developmental toxicity was observed in either of two rabbit 
developmental toxicity studies conducted with tralomethrin. In one 
study, the maternal NOEL was 12.5 mg/kg/day based on mortality while 
the developmental NOEL was judged to be greater than or equal to 25 mg/
kg/day (HDT). In the second study, the maternal NOEL was 8 mg/kg/day 
based on body weight effects while the developmental NOEL was 32 mg/kg/
day (HDT). In a two-generation reproduction study with tralomethrin in 
rats, the parental NOEL was 0.75 mg/kg/day based on body weight 
deficits while the NOEL for offspring was 3.0 mg/kg/day, also based on 
body weight deficits.
    4. Subchronic toxicity-- a. Deltamethrin. A 90-day rat oral 
toxicity study was conducted with deltamethrin which was administered 
by gavage. The NOEL was judged to be 1.0 mg/kg/day based on reduced 
body weight gain and slight hypersensitivity. In a more recent 90-day 
rat dietary study with deltamethrin, the NOEL was judged to be 300 ppm 
(23.9 mg/kg/day for males, 30.5 mg/kg/day for females) 
based on uncoordinated movement, unsteady gait, tremors, increased 
sensitivity to sound, shakes and spasmodic convulsions. The difference 
in the NOEL between the two studies is attributed to the different 
routes of exposure (gavage in oil vs. administered in diet). A 12-week 
study was conducted with deltamethrin in mice. The NOEL was 300 ppm 
(61.5 mg/kg/day in males and 77.0 mg/kg/day in females) 
based on chronic contractions, convulsions, poor condition, decreased 
weight gain and mortality. Two 13-week dog studies were conducted with 
deltamethrin. In the first study, beagle dogs were administered 
deltamethrin by capsule using PEG 200 as a vehicle. The NOEL for this 
study was 1 mg/kg/day based on tremors, unsteadiness, jerking 
movements, salivation, vomiting, liquid

[[Page 50339]]

feces and/or dilatation of the pupils. In the second study, 
deltamethrin was administered by capsule without a vehicle to beagle 
dogs. The NOEL for this study was 10 mg/kg/day based on unsteady gait, 
tremors, head shaking, vomiting and salivation. The difference in 
toxicity between the two studies is attributed to the enhanced 
absorption resulting from the use of PEG 200 as a vehicle in the first 
study. A 21-day dermal toxicity study was conducted with deltamethrin 
in rats. The NOEL for systemic toxicity was determined to be 1,000 mg/
kg/day. In a subchronic inhalation study, rats were exposed to 
aerosolized deltamethrin for 6 hours per day, 5 days per week, for a 
total of 14 days over 3 weeks. Based on slightly decreased body weights 
and neurological effects at higher dose levels, it was concluded that 3 
g/l was the NOEL for systemic effects in this study.
    b. Tralomethrin. Tralomethrin was administrated by gavage in corn 
oil to rats for 13 weeks. Based on mortality, decreased activity and 
motor control, soft stools, labored breathing and significantly lower 
absolute and relative mean liver weights, the NOEL was considered to be 
1 mg/kg/day. Tralomethrin was administered by capsule to beagle dogs 
for 13 weeks. The NOEL for this study was 1.0 mg/kg/day based on 
refusal of milk supplement, tremors, exaggerated patellar response, 
unsteadiness and uncoordinated movement. A 21-day dermal toxicity study 
was conducted with tralomethrin on rats. No systemic effects were 
observed, therefore, the systemic NOEL for this study was 1,000 mg/kg/
day.
    5. Chronic toxicity-- a. Deltamethrin. Deltamethrin was 
administered in the diet to beagle dogs for 2 years. No treatment-
related effects were observed and the NOEL was judged to be 40 ppm 
(1.1 mg/kg/day). In a more recent study, deltamethrin was 
administered by capsule (without a vehicle) to beagle dogs for 1-year. 
The NOEL in this study was considered to be 1 mg/kg/day based on 
clinical signs, decreased food consumption and changes in several 
hematology and blood chemistry parameters. Two rat chronic toxicity/
oncogenicity studies were conducted with deltamethrin. In the first 
study, the test substance was administered via the diet to rats for 2 
years. The NOEL for this study was 20 ppm (1 mg/kg/day) 
based on slightly decreased weight gain. In a more recent study, 
deltamethrin was administered to rats in the diet for 2 years. The NOEL 
for this study was considered to be 25 ppm (1.1 and 1.5 mg/
kg/day for males and females, respectively), based on neurological 
signs, weight gain effects and increased incidence and severity of 
eosinophilic hepatocytes and/or balloon cells. No evidence of 
carcinogenicity was noted in either study. Two mouse oncogenicity 
studies were conducted with deltamethrin. In the first study, 
deltamethrin was administered in the diet for 2 years. No adverse 
effects were observed and the NOEL was judged to be 100 ppm 
(12 and 15 mg/kg/day, respectively, for males and females). 
In a more recent study, deltamethrin was administered in the diet to 
mice for 97 weeks. The NOEL was considered to be 1,000 ppm 
(15.7 and 19.6 mg/kg/day) based on a higher incidence of 
poor physical condition and a slight transient weight reduction. There 
was no evidence of oncogenicity in either study.
    b. Tralomethrin. Tralomethrin was administered to beagle dogs by 
capsule for 1-year at initial dosages of 0, 0.75, 3.0 and 10.0 mg/kg/
day. Due to trembling, ataxia, prostration and convulsions, the high 
dosage was lowered to 8 mg/kg/day at study week 4 and lowered again to 
6 mg/kg/day on study week 14. On the fourteenth week of study, the 0.75 
mg/kg/day dosage was raised to 1.0 mg/kg/day. Based on body weight 
changes, convulsions, tremors, ataxia and salivation, the NOEL for this 
study was considered to be 1 mg/kg/day. Tralomethrin was administered 
by gavage to rats for 24 months. The NOEL for this study was 0.75 mg/
kg/day based on salivation, uncoordinated movement, inability to 
support weight on limbs and decreased body weight parameters. No 
evidence of carcino-genicity was observed. A 2-year mouse oncogenicity 
study was conducted with tralomethrin administered by gavage. The NOEL 
was judged to be 0.75 mg/kg/day based on higher incidences of 
dermatitis and mortality, salivation, uncoordinated involuntary 
movements and aggressiveness. No evidence of oncogenicity was observed.
    6. Animal metabolism-- a. Deltamethrin. The absorption of 
deltamethrin appears to be highly dependent upon the route and vehicle 
of administration. Once absorbed, deltamethrin is rapidly and 
extensively metabolized and excreted, primarily within the first 48 
hours.
    b. Tralomethrin. Tralomethrin is rapidly metabolized to 
deltamethrin after debromination. The metabolic pattern of the 
debrominated tralomethrin is exactly the same as that of the metabolic 
pattern of deltamethrin.
    7. Neurotoxicity. Acute delayed neurotoxicity studies in hens were 
conducted for both deltamethrin and tralomethrin. In both cases, the 
study results were negative indicating that neither material causes 
delayed neurotoxicity.
    8. Endocrine effects. No special studies have been conducted to 
investigate the potential of deltamethrin or tralomethrin to induce 
estrogenic or other endocrine effects. However, the standard battery of 
required toxicity studies has been completed. These studies include an 
evaluation of the potential effects on reproduction and development, 
and an evaluation of the pathology of the endocrine organs following 
repeated or long-term exposure. These studies are generally considered 
to be sufficient to detect any endocrine effects, yet no such effects 
were detected. Thus, the potential for deltamethrin or tralomethrin to 
produce any significant endocrine effects is considered to be minimal.

C. Aggregate Exposure

    Based on the fact that tralomethrin is rapidly metabolized in 
plants and animals to deltamethrin, and the toxicological profile of 
the two compounds is similar, it is appropriate to consider combined 
exposure assessments for tralomethrin and deltamethrin. Deltamethrin 
and tralomethrin are broad spectrum insecticides used to control pests 
of crops, ornamental plants and turf, and domestic indoor and outdoor 
(including dog collars), commercial, and industrial food use areas. 
Thus, aggregate non-occupational exposure would include exposures 
resulting from non-food uses in addition to consumption of potential 
residues in food and water. Exposure via drinking water is expected to 
be negligible since deltamethrin binds tightly to soil and rapidly 
degrades in water.
    1. Dietary exposure-- a. Food. Food tolerances have been 
established (with expiration dates of November 15, 1997), for residues 
of tralomethrin and/or deltamethrin and its metabolites in or on a 
variety of raw agricultural commodities. These tolerances, in support 
of registrations, currently exist for residues of tralomethrin on 
broccoli, cottonseed, head lettuce, leaf lettuce, soybeans, sunflower 
seed, and cottonseed oil. Also, such tolerances, in support of 
registrations, currently exist for deltamethrin on cottonseed and 
cottonseed oil. Additionally, tolerances which are not time-limited 
have been established for tralomethrin to support its use in food/feed 
handling establishments, and for deltamethrin on tomatoes and 
concentrated tomato products to support the importation of tomato 
commodities treated with deltamethrin. Further, a food/feed

[[Page 50340]]

handling establishment use, and associated tolerances, is pending for 
deltamethrin. Potential acute exposures from food commodities were 
estimated using a Tier 3 acute dietary risk assessment (Monte Carlo 
Analysis) following EPA guidance. Potential chronic exposures from food 
commodities under the established food and feed additive tolerances for 
deltamethrin and tralomethrin, plus the pending tolerances for 
deltamethrin associated with use in food/feed handling areas, were 
estimated using NOVIGEN's DEEM (Dietary Exposure Evaluation Model). 
This chronic risk assessment was conducted using anticipated residues 
based on field trial or monitoring data, percent crop treated, and 
percent food handling establishments treated.
    b. Drinking water. Tralomethrin and deltamethrin are immobile in 
soil and, therefore, will not leach into groundwater. Additionally, due 
to the insolubility and lipophilic nature of deltamethrin and 
tralomethrin, 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 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.
    2. Non-dietary exposure. As noted above, deltamethrin and 
tralomethrin are broad spectrum insecticides registered for use on a 
variety of food and non-food agricultural commodities. Additionally, 
registrations are held for non-agricultural applications including turf 
and lawn care treatments, broadcast carpet treatments (professional use 
only), indoor fogger, spot, crack and crevice treatments, insect baits, 
lawn and garden sprays and indoor and outdoor residential, industrial 
and institutional sites including those for Food/Feed Handling 
Establishments.
    To evaluate non-dietary exposure, the ``flea infestation control'' 
senario was chosen to represent a plausible but worst case non-dietary 
(indoor and outdoor) non-occupational exposure. This scenario provides 
a situation where deltamethrin and/or tralomethrin is commonly used and 
they can be used concurrently for a multitude of uses, e.g., spot and/
or broadcast treatment of infested indoor surfaces such as carpets and 
rugs, treatment of pets and treatment of the lawn. This hypothetical 
situation provides a very conservative, upper bound estimate of 
potential non-dietary exposures. Consequently, if health risks are 
acceptable under these conditions, the potential risks associated with 
other more likely scenarios would also be acceptable.
    Because tralomethrin is rapidly metabolized to deltamethrin, and 
the toxicology profiles of deltamethrin and tralomethrin are virtually 
identical, a non-dietary and aggregate (non-dietary + chronic dietary) 
exposure/risk assessment has been conducted for the combination of both 
active ingredients. The total exposure to both materials was expressed 
as ``deltamethrin equivalents'' and these were compared to the 
toxicology endpoints identified for deltamethrin.

C. Cumulative Effects

    When considering a tolerance, the Agency must consider ``available 
information'' concerning the cumulative effects of a particular 
pesticides residues and ``other substances that have a common mechanism 
of toxicity''. AgrEvo USA Company, acting as registered US agent for 
Hoechst Schering AgrEvo SA, believes that ``available information'' in 
this context includes not only toxicity, chemistry, and exposure data, 
but also scientific policies and methodologies for understanding common 
mechanisms of toxicity and conducting cumulative risk assessments.
    Further, AgrEvo does not have, at this time, available data to 
determine whether tralomethrin and/or deltamethrin have a common 
mechanism of toxicity with other substances. For the purposes of this 
tolerance action, therefore, no assumption has been made that 
tralomethrin and/or deltamethrin have a common mechanism of toxicity 
with other substances.
    AgrEvo USA Company, acting as registered US agent for Hoechst 
Schering AgrEvo SA, will submit information for EPA to consider 
concerning potential cumulative effects of deltamethrin and/or 
tralomethrin consistent with the schedule established by EPA at 62 FR 
42020 (August 4, 1997,) and other EPA publications pursuant to the Food 
Quality Protection Act (FQPA).

D. Safety Determination

    1. U.S. population. The toxicity and residue data base for 
deltamethrin and tralomethrin are considered to be valid, reliable and 
essentially complete according to existing regulatory requirements. No 
evidence of oncogenicity has been observed for either compound. For 
acute exposures, the toxicology endpoint from the deltamethrin rat 
development toxicity study, 3.3 mg/kg/day, is used. For chronic 
exposures to deltamethrin and tralomethrin, the Reference Dose (RfD) of 
0.01 mg/kg bodyweight/day established for deltamethrin based on the 
NOEL from the 2-year rat feeding study and a 100-fold safety factor to 
account for interspecies extrapolation and intraspecies variation is 
used.
    For the overall U.S. population, acute dietary exposure at the 
99.9th percentile results in a Margin of Exposure (MOE) of 5,382; the 
MOE for the 99th percentile is 16,661; and at the 95th percentile the 
MOE is 57,470. For the overall US population, chronic dietary exposure 
results in a utilization of 0.2 percent of the reference dose. Using an 
upper bound estimate of potential non-dietary exposures for a worst 
case scenario (flea treatment) results in an MOE of 160,000 for adults. 
Utilizing the scenario of chronic dietary exposure plus an upper bound 
estimate of potential non-dietary exposure from a worst case scenario 
(flea treatment), it is shown that for aggregate exposure to 
deltamethrin and tralomethrin there is an MOE of 83,000 for adults. 
There is generally no concern for MOE greater than 100. For chronic 
exposure, there is generally no concern for exposure below 100 percent 
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.
    In conclusion, there is reasonable certainty that no harm will 
result to the U.S. population, in general, from dietary or aggregate 
exposure to either deltamethrin and/or tralomethrin.
    2. Infants and children. Data from developmental toxicity studies 
in rats and rabbits, and multigeneration reproduction studies in rats 
are generally used to assess the potential for increased sensitivity of 
infants and children. The developmental toxicity studies are designed 
to evaluate adverse effects on the developing organism

[[Page 50341]]

resulting from pesticide exposure during prenatal development. 
Reproduction studies provide information relating to reproductive and 
other effects on adults and offspring from pre-natal and post-natal 
exposure to the pesticide. None of these studies conducted with 
deltamethrin or tralomethrin indicated developmental or reproductive 
effects as a result of exposure to these materials.
    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 toxicity and the completeness of the 
database. Based on the current toxicological data requirements, the 
database relative to pre- and post-natal effects in children is 
complete. Although no indication of increased susceptibility to younger 
animals was noted in any of the above studies, or in the majority of 
studies with other pyrethroids, several recent publications have 
reported that deltamethrin is more toxic to neonate and weanling 
animals than to adults. However, a joint industry group currently 
investigating this issue was unable to reproduce these findings. 
Furthermore, the RfD (0.01 mg/kg/day) that has been established for 
deltamethrin is already more than 1,000-fold lower than the lowest NOEL 
from the developmental and reproduction studies. Therefore, the RfD of 
0.01 mg/kg/day is appropriate for assessing chronic aggregate risk to 
infants and children and an additional uncertainty factor is not 
warranted. Also, the NOEL of 3.3 mg/kg/day from the rat developmental 
toxicity study is appropriate to use in acute dietary, short term non-
dietary, and aggregate exposure assessments.
    For the population subgroup described as non-nursing infants, less 
than 1 year old, the MOE for acute dietary exposure at the 99.9th 
percentile is 13,853; at the 99th percentile the MOE is 74,022; and at 
the 95th percentile the MOE is 663,629. For the population subgroup 
described as children 1-6 years old, the MOE for acute dietary exposure 
is 2,300 for the 99.9th percentile; at the 99th percentile the MOE is 
10,409; and at the 95th percentile the MOE is 42,070. For non-nursing 
infants, chronic dietary exposure results in a utilization of 0.3 
percent of the reference dose, and for children 1-6 years old 0.4 
percent of the reference dose is utilized. Using an upper bound 
estimate of potential non-dietary exposures for a worst case scenario 
(flea treatment) results in an MOE of 6,100 for infants less than 1 
year old, and an MOE of 6,600 for children 1-6 years old. Utilizing the 
scenario of chronic dietary exposure plus an upper bound estimate of 
potential non-dietary exposure from a worst case scenario (flea 
treatment) it is shown that for aggregate exposure to deltamethrin and 
tralomethrin, there is an MOE of 5,800 for infants less than 1-year 
old, and an MOE of 6,100 for children 1-6 years old. There is generally 
no concern for MOE s greater than 100. For chronic exposure, there is 
generally no concern for exposure below 100 percent 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.
    In summary, there is reasonable certainty that no harm will result 
to infants and children from aggregate exposure to either deltamethrin 
or tralomethrin.

E. International Tolerances

    The proposed/established CODEX maximum residue levels (MRL) and for 
deltamethrin are as follows: cotton at 0.05 ppm and food/feed handling 
uses at 0.05 ppm. As far as can be determined at this time, no CODEX 
MRL's are established or proposed for tralomethrin.

F. Conclusions

    The existing tolerances for deltamethrin and tralomethrin do not 
pose a significant risk to human health, including that of children, 
and are in compliance with the requirements of the FQPA of 1996. 
Therefore, the time limitations associated with these tolerances can be 
removed. (John Hebert)

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)

3. DuPont Agricultural Products

PP-7F2013

    EPA has received a request from DuPont Agricultural Products, P. O. 
Box 80038, Wilmington, DE 19880-0038 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 a 
tolerance established for residues of the insecticide and pyrethroid 
fenvalerate, including the s,s-enriched isomer esfenvalerate 
(Asana XL Insecticide), ((S)-cyano-(3-phenoxyphenyl)methyl 
(S)-4-chloro-alpha-(1-methylethyl)benzeneacetate in or on the raw 
agricultural commodity cottonseed at 0.2 parts per million (ppm). The 
tolerance was originally requested in PP-7F2013. 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 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 chromatography with nitrogen phosphorous 
detection available for enforcement with a limit of detection that 
allows monitoring food with residues at or above tolerance levels.
    3. Magnitude of residues. 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. for agricultural use. Since 
the S,S-isomer is the insecticidally active isomer, the use rate for 
Asana is four times lower than that for Pydrin . A 
petition is pending (PP-4F4329), to convert tolerances (still to be 
expressed as the sum of all isomers) based on the use rates for 
Asana. Bridging residue studies have shown Asana 
residues to be 3-4 times lower than Pydrin residues.
    EPA has established a tolerance of 0.2 ppm for fenvalerate on 
cottonseed. Magnitude of residue and processing studies support this 
tolerance. This request is for the removal of the time limitation 
currently imposed on the tolerance of 0.2 ppm for fenvalerate on 
cottonseed.

B. Toxicological Profile

    The following studies have been submitted to EPA:
    1. Acute toxicity. A rat acute oral study on esfenvalerate 
technical has an LD50 of 87.2 milligram (mg)/kilogram (kg). 
A rabbit acute dermal study on esfenvalerate has an LD50 of 
>2,000 mg/kg. Acute inhalation on technical grade active ingredient 
(a.i.) waived due to negligible vapor pressure. A primary eye 
irritation test using esfenvalerate in the rabbit showed mild 
irritation (conjunctivitis) that cleared by day 7. A primary dermal 
irritation test using esfenvalerate in the rabbit which showed minimal 
irritation that reversed within 72 hours after treatment. A dermal 
sensitization test on esfenvalerate in guinea pigs which showed no 
sensitization.
    2. Genotoxicty. Esfenvalerate was not mutagenic in reverse mutation 
assays in Salmonella and E. Coli in vitro assay in Chinese hamster lung 
cells. Esfenvalerate did not induce chromosome aberrations in an in 
vitro assay in Chinese hamster ovary cells. Esfenvalerate did not 
induce micronuclei in bone marrow of mice given up to 150 mg/kg 
intraperitoneally. Esfenvalerate did not induce unscheduled DNA 
synthesis in HeLa cells.
    3. Reproductive and developmental toxicity. In a pilot 
developmental study in the rat with doses of 0, 1, 2, 3, 4, 5, and 20 
mg/kg/day esfenvalerate maternal clinical signs of abnormal gait or 
mobility occurred at 4 mg/kg/day and above. In a developmental study in 
the rat with doses of 0, 2.5, 5, 10, and 20 mg/kg/day esfenvalerate by 
gavage 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 was no maternal No-Observed-Effect-Level 
(NOEL) in the main study but a NOEL of 2 mg/kg/day was established on 
the pilot study. 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.
    In 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. The maternal NOEL 
was 2 mg/kg/day based on excessive grooming at 3 mg/kg/day and above. 
In a developmental study in the rabbit with doses of 0, 3, 10, and 20 
mg/kg/day esfenvalerate by gavage there was no maternal NOEL in the 
main study, but a maternal NOEL of 2 mg/kg/day 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 two-generation feeding study with esfenvalerate in the rat at 
dietary levels of 0, 75, 100, or 300 ppm. The high 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 No-Observed-Adverse-Effect-Level (NOAEL) for both adult 
rats and their offspring. Effects were observed in adults and pups of 
both generations at 100 ppm and above. Pups

[[Page 50345]]

were no more sensitive than adult animals.
    4. Subchronic toxicity. A 90-day feeding study in rats was 
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.
    A 90-day feeding study in mice was 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.
    A 3-month subchronic study in dogs is satisfied by a 1-year oral 
study in dogs, in which the NOEL was 200 ppm (5 mg/kg/day).
    A 21-day dermal study in rabbits with fenvalerate was conducted at 
100, 300, and 1,000 mg/kg/day with an NOAEL of 1,000 mg/kg/day.
    5. Chronic toxicity. In 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). 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.
    In a 20-month study with fenvalerate in mice fed 0, 10, 30, 100, 
and 300 ppm the NOEL was 30 ppm ( 6 mg/kg/day) based on red 
blood cell effects and granulomatous changes at 100 ppm. Fenvalerate 
was not carcinogenic at any concentration.
    In a 18-month study in mice fed 0, 35, 150, and 350 ppm 
esfenvalerate. Mice fed the 350 ppm dose were sacrificed within the 
first two months of the study, after excessive morbidity and mortality 
due to self-trauma induced by pharmacological effects related to skin 
stimulation. 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 did not produce carcinogenicity.
    In 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.
    EPA has classified esfenvalerate in Group E--evidence of 
noncarcinogenicity for humans.
    6. Animal metabolism. After oral dosing with fenvalerate, the 
majority of the administered radioactivity was eliminated in the 
initial 24 hours. The metabolic pathway involved cleavage of the ester 
linkage followed by hydroxylation, oxidation, and conjugation of the 
acid and alcohol moieties.
    7. Metabolite toxicology. The parent molecule is the only moiety of 
toxicological significance appropriate for regulation in plant and 
animal commodities.
    8. Endocrine 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. There have been no effects on offspring in 
developmental toxicity studies.

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 toxicological 
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 in these studies.
    2. Food. A chronic dietary exposure assessment using anticipated 
residues and monitoring data and adjusting for percent crop treated, 
found the percentages of the Reference Dose (RfD) utilized by the most 
sensitive sub-population (children 1-6 years) to be 5.2%. Chronic 
exposure for the overall U.S. population was 2.1% of the RfD. This 
assessment included pending tolerances and all food tolerances for 
incidental residues from use in food handling establishments.
    A Tier 3 acute dietary assessment indicated the most sensitive sub-
population was children 1-6 years with Margin of Exposures (MOEs) of 
352, 200, and 103 at the 95th, 99th, and 
99.9th percentile of exposure, respectively. The MOEs for 
nursing infants are 410, 199, and 151 at the 95th, 
99th, and 99.9th percentile of exposure, 
respectively. The MOEs for non-nursing infants are 661, 270, and 134 at 
the 95th, 99th, and 99.9th percentile 
of exposure, respectively. The MOEs for the general population are 742, 
352, and 170 at the 95th, 99th, and 
99.9th percentile of exposure, respectively. This analysis 
used field trial data to estimate exposure and market share information 
for the percent of crop treated. It used Monte Carlo modeling and 
appropriate processing factors for processed food and distribution 
analysis. Food handling establishment commodities are not relevant to 
this type of analysis and 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.
    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 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 pound model since drinking water derived from 
surface water would be treated before consumption. Based on these 
analyses, the contribution of water to the dietary risk estimate is 
negligible.
    4. Non-dietary exposure. Esfenvalerate is registered for non-crop 
uses including spray treatments in and around commercial and 
residential areas, treatments for control of ectoparasites on pets, 
home care products including foggers, pressurized sprays, crack and 
crevice treatments, lawn and garden sprays, and pet and pet bedding 
sprays. For the non-agricultural

[[Page 50346]]

products, the very low amounts of active ingredient they contain, 
combined with the low vapor pressure (1.5 x 10-9 millimeters 
(mm) Mercury at 25 deg.C) and low dermal penetration, would result in 
minimal inhalation and dermal exposure.
    Individual non-dietary risk exposure analyses were conducted using 
a flea infestation scenario that included pet spray, carpet and room 
treatment, and lawn care, respectively. The pet spray product 
assessment indicated MOEs of 740,000, 2,600, and 2,500 for adults, 
children 1-6 years, and children < 1 year, respectively. The carpet and 
room treatment assessment indicated MOEs of 110,000, 4,500, and 4,200 
for adults, children 1-6 years, and children < 1 year, respectively. 
The lawn care assessment indicated MOEs of 700,000, 26,000, and 24,000 
for adults, children 1-6 years, and children < 1 year, respectively.
    5. Aggregate exposure-- Dietary and non-dietary. Based on the 
toxicity endpoints selected for esfenvalerate, absorbed doses were 
combined and compared to the relevant systemic NOEL for estimating 
MOEs.
    The non-dietary risk analysis MOEs combined with the chronic 
dietary risk analysis MOEs indicated aggregate MOEs of 4,400, 860, and 
1,000 for adults, children 1-6 years, and children < 1 year, 
respectively.
    It is important to acknowledge that these MOEs are likely to 
significantly underestimate the actual MOEs due to a variety of 
conservative assumptions and biases inherent in the exposure assessment 
methods used for their derivation. Therefore, it can be concluded that 
the potential non-dietary and dietary aggregate exposures for 
esfenvalerate are associated with a substantial degree of safety. The 
aggregate risk analyses demonstrate compliance with the health-based 
requirements of the Food Quality Protection Act of 1996 (FQPA) (7 
U.S.C. 136 note) and supports the continued registration and use of 
residential, agricultural, and commercial products containing this a.i.

D. Cumulative Effects

    Section 408(b)(2)(D)(v) of the FFDCA requires that, when 
considering whether to establish, modify, or revoke a tolerance, the 
Agency consider ``available information'' concerning the cumulative 
effects of a particular pesticide's residues and ``other substances 
that have a common mechanism of toxicity''. At this time, available 
methodologies do not exist to resolve the complex scientific issues 
concerning common mechanism of toxicity of pyrethroids in a meaningful 
way. DuPont intends to submit information for EPA to consider 
concerning potential cumulative effects of esfenvalerate 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.
    In consideration of potential cumulative effects of esfenvalerate 
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 esfenvalerate 
would be cumulative with those of other chemical compounds. In 
addition, since esfenvalerate does not appear to produce a toxic 
metabolite produced by other substances; only the potential risks of 
esfenvalerate have been considered in this assessment of its aggregate 
exposure.

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. In addition, no other studies 
conducted with fenvalerate or esfenvalerate indicate that immature 
animals are more sensitive than adults. Therefore, the safety factor 
used for protection of adults is fully appropriate for the protection 
of infants and children; no additional safety factor is necessary.
    1. U.S. population. A chronic dietary exposure assessment using 
anticipated residues, monitoring information, and percent crop treated 
indicated the percentage of the RfD utilized by the general population 
to be 2.1%. There is generally no concern for exposures below 100% of 
the RfD because the RfD represents the level at or below which daily 
aggregate dietary exposure over a lifetime will not pose appreciable 
risks to human health.
    For acute exposure, a MOE of greater than 100 is considered an 
adequate MOE. A Tier 3 acute dietary exposure assessment found the 
general population to have MOE's of 742, 352, 170 at the 
95th, 99th, and 99.9th percentile of 
exposure, respectively. These values were generated using actual field 
trial residues and market share data for percentage of crop treated. 
These results depict an accurate exposure pattern at an exaggerated 
daily dietary exposure rate.
    The aggregate exposure to use of esfenvalerate as pet spray, carpet 
treatment, lawn care, and in the diet indicated an MOE of 4,400 for 
adults.
    Therefore, there is a reasonable certainty that no harm will result 
from chronic dietary, acute dietary, non-dietary, or aggregate exposure 
to esfenvalerate residues.
    2. Infants and children. A chronic dietary exposure assessment 
found the percentages of the RfD utilized by the most sensitive sub-
population to be 5.2% for children 1-6 years. The acute dietary 
exposure assessment found the most sensitive sub-population to be 
children 1-6 years with MOEs of 352, 200, and 103 at the 
95th, 99th, and 99.9th percentile of 
exposure, respectively. Nursing infants had MOEs of 410, 199, and 151 
at the 95th, 99th, and 99.9th 
percentile of exposure, respectively. Non-nursing infants had MOEs of 
661, 270, and 134 at the 95th, 99th, and 
99.9th percentile of exposure, respectively. The aggregate 
exposure to use of esfenvalerate as pet spray, carpet treatment, lawn 
care, and in the diet indicated an MOE of 860 for children 1-6 years 
and an MOE of 1,000 for children < 1 year.
    Thus, there is reasonable certainty that no harm to infants and 
children will result from chronic dietary, acute dietary, non-dietary, 
or 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 desirable. (John Hebert)

4. FMC Corporation

PP 2F2623, 4F2986, 3F2824, 7F3498, and 4F3011

    EPA has received a request regarding pesticide petitions (PP 
2F2623, 4F2986, 3F2824, 7F3498, and 4F3011) from FMC Corporation, 1735 
Market Street, Philadelphia, PA 19103. The request proposes to remove 
any time limitations on established tolerances for residues of the 
insecticide zeta-cypermethrin (s-Cyano(3-phenoxyphenyl)methyl 
() cis, trans 3-(2,2-dichloroethenyl)-2,2-
dimethylcyclopropanecarboxylate) in or on the raw agricultural 
commodities cottonseed at 0.5 ppm, pecans 0.05 ppm, lettuce, head at 
10.0 ppm, onions, bulb at 0.10 ppm and cabbage at 2.0 ppm (established 
at 40 CFR 180.418). These tolerances were established under (PP) 
2F2623, 4F2986, 3F2824, 7F3498, and 4F3011. EPA has determined that the 
request contains data or information regarding the elements set forth 
in

[[Page 50347]]

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 cypermethrin in plants is 
adequately understood. Studies have been conducted to delineate the 
metabolism of radiolabelled cypermethrin 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 cypermethrin 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).
    3. Magnitude of residues. Crop field trial residue data from 
studies conducted at the maximum label rates for cotton, pecans, head 
lettuce, bulb onions, and cabbage show that the established 
cypermethrin tolerances on cottonseed of 0.5 ppm, pecans 0.05 ppm, 
lettuce, head at 10.0 ppm, onions, bulb at 0.10 ppm and cabbage at 2.0 
ppm, will not be exceeded when the zeta-cypermethrin 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 NOEL of 0.5 mg/kg/day based on the NOEL of 1.0 
mg/kg/day from the cypermethrin chronic toxicity study in dogs and a 
correction factor of two to account for the differences in the 
percentage of the biologically active isomer. The LOEL of this study of 
5.0 mg/kg/day was based on gastrointestinal disturbances observed in 
the first week of the study. This acute dietary endpoint is used to 
determine acute dietary risks to all population subgroups.
    2. Genotoxicity. The following genotoxicity tests were all 
negative: in vivo chromosomal aberration in rat bone marrow cells; in 
vitro cytogenic chromosome aberration; unscheduled DNA synthesis; CHO/
HGPTT mutagen assay; weakly mutagenic: gene mutation (Ames).
    3. Reproductive and developmental toxicity. No evidence of 
additional sensitivity to young rats was observed following pre- or 
postnatal exposure to zeta-cypermethrin.
    a. A two-generation reproductive toxicity study with zeta-
cypermethrin in rats demonstrated a NOEL of 7.0 mg/kg/day and a LOEL of 
27.0 mg/kg/day for parental/systemic toxicity based on body weight, 
organ weight, and clinical signs. There were no adverse effects in 
reproductive performance. The NOEL for reproductive toxicity was 
considered to be > 45.0 mg/kg/day (the highest dose tested).
    b. A developmental study in rats demonstrated a maternal NOEL of 
12.5 mg/kg/day and a LOEL of 25 mg/kg/day based on decreased maternal 
body weight gain, food consumption and clinical signs. There were no 
signs of developmental toxicity at 35.0 mg/kg/day, the highest dose 
level tested.
    c. A developmental study with cypermethrin in rabbits demonstrated 
a maternal NOEL of 100 mg/kg/day and a LOEL of 450 mg/kg/day based on 
decreased body weight gain. There were no signs of developmental 
toxicity at 700 mg/kg/day, the highest dose level tested.
    4. Subchronic toxicity--Short- and intermediate-term toxicity. The 
systemic NOEL of 2.5 mg/kg/day based on the systemic NOEL of 5.0 mg/kg/
day from the cypermethrin chronic toxicity study in dogs and a 
correction factor of two to account for the biologically active isomer 
would also be used for short- and intermediate-term MOE calculations 
(as well as acute, discussed in (1) above). This NOEL was based on 
neurotoxic clinical signs observed in the first week of treatment of 
the study.
    5. Chronic toxicity--a. The RfD has been established at 0.0050 mg/
kg/day. This RfD is based on a cypermethrin chronic toxicity study in 
dogs with a NOEL of 1.0 mg/kg/day, based on gastrointestinal 
disturbances observed at the LOEL of 5.0 mg/kg/day during the first 
week of the study; an uncertainty factor of 200 is used to account for 
the differences in the percentage of the biologically active isomer.
    b. Cypermethrin is classified as a Group C chemical (possible human 
carcinogen with limited evidence of carcinogenicity in animals) based 
upon limited evidence for carcinogenicity in female mice; assignment of 
a Q* has not been recommended.
    6. Animal metabolism. The metabolism of cypermethrin in animals is 
adequately understood. Cypermethrin has been shown to be rapidly 
absorbed, distributed, and excreted in rats when administered orally. 
Cypermethrin is metabolized by hydrolysis and oxidation.
    7. Metabolite toxicology. The Agency has previously determined that 
the metabolites of cypermethrin 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 cypermethrin 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 cypermethrin has an adverse effect on the 
endocrine system.

C. Aggregate Exposure

    1. Dietary exposure--a. Food. Tolerances have been established for 
the residues of the insecticide zeta-cypermethrin, in or on a variety 
of raw agricultural commodities. Tolerances, in support of 
registrations, currently exist for residues of zeta-cypermethrin on 
cottonseed; pecans; lettuce, head; onions, bulb; and cabbage and 
livestock commodities of cattle, goats, hogs, horses, and sheep. For 
the purposes of assessing the potential dietary exposure for these 
existing tolerances, FMC has utilized available information on 
anticipated residues, monitoring data and percent crop treated as 
follows:
    b. 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 one day or single exposure. For the purposes of assessing acute 
dietary risk for zeta-cypermethrin, FMC has used the NOEL of 0.5 mg/kg/
day based on the NOEL of 1.0 mg/kg/day from the cypermethrin chronic 
toxicity study in dogs and a correction factor of two to account for 
the differences in the percentage of the biologically active isomer. 
The LOEL of this study of 5.0 mg/kg/day was based on gastrointestinal 
disturbances observed in the first week of the study.
    This acute dietary endpoint is 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 
margins of exposure (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 0.000528 mg/kg/day (MOE of 947); 99th 
percentile 0.001746 mg/kg/day (MOE of 286); and 99.9th 
percentile 0.004069 mg/kg/day (MOE of 123).

[[Page 50348]]

    The 95th percentile of exposure for all infants < 1 year old was 
estimated to be 0.000560 mg/kg/day (MOE of 892); 99th 
percentile 0.000885 mg/kg/day (MOE of 565); and 99.9th 
percentile 0.001260 mg/kg/day (MOE of 397).
    The 95th percentile of exposure for nursing infants < 1 year old 
was estimated to be 0.000207 mg/kg/day (MOE of 2,417); 99th 
percentile 0.000569 mg/kg/day (MOE of 879); and 99.9th 
percentile 0.001442 mg/kg/day (MOE of 347).
    The 95th percentile of exposure for non-nursing infants < 1 year 
old was estimated to be 0.000607 mg/kg/day (MOE of 824); 
99th percentile 0.000925 mg/kg/day (MOE of 540); and 
99.9th percentile 0.001190 mg/kg/day (MOE of 420).
    The 95th percentile of exposure for children 1 to 6 years old and 7 
to 12 years old (the most highly exposed population subgroup) was 
estimated to be, respectively, 0.000740 mg/kg/day (MOE of 676) and 
0.000596 mg/kg/day (MOE of 839); 99th percentile 0.001856 
mg/kg/day (MOE of 269) and 0.002047 mg/kg/day (MOE 244); and 
99.9th percentile 0.005021 mg/kg/day (MOE of 100) and 
0.004843 (MOE of 103). Therefore, FMC concludes that the acute dietary 
risk of zeta-cypermethrin, as estimated by the dietary risk assessment, 
does not appear to be of concern.
    c. Chronic exposure and risk. The acceptable reference dose (RfD) 
of 0.0050 mg/kg/day for zeta-cypermethrin is based on a NOEL of 1.0 mg/
kg/day from the cypermethrin chronic dog study and an uncertainty 
factor of 200 (used to account for the differences in the percentage of 
the biologically active isomer). The endpoint effect of concern were 
based on gastrointestinal disturbances observed in the first week of 
the study at the LOEL of 5.0 mg/kg/day. A chronic dietary exposure/risk 
assessment has been performed for zeta-cypermethrin 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 
0.000017 mg/kg body weight (bwt)/day and utilize 0.3 percent of the RfD 
for the overall U. S. population. The ARC for non-nursing infants (<1 
year) and nursing infants (<1 year) are estimated to be 0.000011 mg/kg/
day and 0.000002 mg/kg/day and utilizes 0.2 percent and 0 percent of 
the RfD, respectively. The ARC for children 1-6 years old and children 
7-12 years old (subgroups most highly exposed) are estimated to be 
0.000027 mg/kg bwt/day and 0.000022 mg/kg bwt/day and utilizes 0.5 
percent and 0.4 percent 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 percent of the RfD. Therefore, FMC concludes that the 
chronic dietary risk of cypermethrin, as estimated by the dietary risk 
assessment, does not appear to be of concern.
    2. Drinking water. Laboratory and field data have demonstrated that 
cypermethrin is immobile in soil and will not leach into groundwater. 
Other data show that cypermethrin 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 (<<0.001 
parts per billion).
    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 parts per billion. 
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. Zeta-cypermethrin is registered for 
agricultural crop applications only, therefore non-dietary exposure 
assessments are not warranted.

D. Cumulative Effects

    In consideration of potential cumulative effects of cypermethrin 
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 cypermethrin 
would be cumulative with those of other chemical compounds; thus only 
the potential risks of cypermethrin 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 
cypermethrin consistent with the schedule established by EPA at 62 FR 
42020 (August 4, 1997) and other EPA publications pursuant to the Food 
Quality Protection Act.

E. Safety Determination

    1. U.S. population. Based on a complete and reliable toxicology 
database, the acceptable reference dose (RfD) for zeta-cypermethrin is 
0.0005 mg/kg/day, based on a NOEL of 1.0 mg/kg/day and a LOEL of 5.0 
mg/kg/day from the cypermethrin chronic dog study and an uncertainty 
factor of 200. 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 
0.000017 mg/kg body weight (bwt)/day and utilize 0.3 percent of the RfD 
for the overall U. S. population. The ARC for non-nursing infants (<1 
year) and nursing infants (<1 year) are estimated to be 0.000011 mg/kg/
day and 0.000002 mg/kg/day and utilizes 0.2 percent and 0 percent of 
the RfD, respectively. The ARC for children 1-6 years old and children 
7-12 years old (subgroups most highly exposed) are estimated to be 
0.000027 mg/kg bwt/day and 0.000022 mg/kg bwt/day and utilizes 0.5 
percent and 0.4 percent 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 percent of the RfD. Therefore, FMC concludes that the 
chronic dietary risk of zeta-cypermethrin, as estimated by the 
aggregate risk assessment, does not appear to be of concern.
    For the overall U.S. population, the calculated margins of exposure 
(MOE) at the 95th percentile was estimated to be 947; 286 at the 
99th percentile; and 123 at the 99.9th 
percentile.
    For all infants < 1 year old, the calculated margins of exposure 
(MOE) at the 95th percentile was estimated to be 892; 565 at the 
99th percentile; and 397 at the 99.9th 
percentile.
    For nursing infants < 1 year old, the calculated margins of 
exposure (MOE) at

[[Page 50349]]

the 95th percentile was estimated to be 2,417; 879 at the 
99th percentile; and 347 at the 99.9th 
percentile.
    For non-nursing infants < 1 year old, the calculated margins of 
exposure (MOE) at the 95th percentile was estimated to be 824; 540 at 
the 99th percentile; and 420 at the 99.9th 
percentile. For the most highly exposed population subgroups, children 
1-6 years old and children 7-12 years old, the calculated MOEs at the 
95th percentile were estimated to be, respectively, 676 and 839; 269 
and 244 at the 99th percentile; and 100 and 103 at the 
99.9th percentile. Therefore, FMC concludes that there is 
reasonable certainty that no harm will result from acute exposure to 
zeta-cypermethrin.
    2. Infants and children-- a. General. In assessing the potential 
for additional sensitivity of infants and children to residues of zeta-
cypermethrin, FMC considered data from developmental toxicity studies 
in the rat and rabbit, and a two-generation reproductive study in the 
rat. The data demonstrated no indication of increased sensitivity of 
rats to zeta-cypermethrin or rabbits to cypermethrin in utero and/or 
postnatal exposure to zeta-cypermethrin or cypermethrin. 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 database.
    b. Developmental toxicity studies. In the prenatal developmental 
toxicity studies in rats and rabbits, there was no evidence of 
developmental toxicity at the highest doses tested (35.0 mg/kg/day in 
rats and 700 mg/kg/day in rabbits). Decreased body weight gain was 
observed at the maternal LOEL in each study; the maternal NOEL was 
established at 12.5 mg/kg/day in rats and 100 mg/kg/day in rabbits.
    c. Reproductive toxicity study. In the two-generation reproduction 
study in rats, offspring toxicity (body weight) and parental toxicity 
(body weight, organ weight, and clinical signs) was observed at 27.0 
mg/kg/day and greater. The parental systemic NOEL was 7.0 mg/kg/day and 
the parental systemic LOEL was 27.0 mg/kg/day. There were no 
developmental (pup) or reproductive effects up to 45.0 mg/kg/day, 
highest dose tested.
    d. Pre- and post-natal sensitivity-- i. Pre-natal. There was no 
evidence of developmental toxicity in the studies at the highest doses 
tested in the rat (35.0 mg/kg/day) or in the rabbit (700 mg/kg/day). 
Therefore, there is no 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.

F. 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 and 
children. As stated above, aggregate exposure assessments utilized 
significantly less than 1 percent 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 cypermethrin residues.
    Subchronic toxicity-- Short- and intermediate-term toxicity. The 
systemic NOEL of 2.5 mg/kg/day based on the systemic NOEL of 5.0 mg/kg/
day from the cypermethrin chronic toxicity study in dogs and a 
correction factor of two to account for the biologically active isomer 
would also be used for short- and intermediate-term MOE calculations 
(as well as acute, discussed in (1) above). This NOEL was based on 
neurotoxic clinical signs observed in the first week of treatment of 
the study.

G. International Tolerances

     There are no Codex, Canadian, or Mexican residue limits for 
residues of zeta-cypermethrin in or on cotton, pecans, lettuce, head, 
onions, bulb, or cabbage. (Stephanie Willett)

5. FMC Corporation

PP 2F2623, 4F2986, 3F2824, 7F3498, 4F3011, 4F4291

    EPA has received a request regarding (PP 2F2623, 4F2986, 3F2824, 
7F3498, 4F3011, 4F4291) from FMC Corporation, 1735 Market Street, 
Philadelphia, PA 19103. The request proposes to remove any time 
limitations on established tolerances for residues of the insecticide 
cypermethrin (-alpha -Cyano(3-phenoxyphenyl)methyl 
()  cis,  trans  3-(2,2-dichloroethenyl)-2,2-
dimethylcyclopropanecarboxylate) in or on the raw agricultural 
commodities cottonseed at 0.5 ppm, pecans 0.05 ppm, lettuce, head at 
10.0 ppm, onions, bulb at 0.10 ppm, cabbage at 2.0 ppm,  Brassica, head 
and stem at 2.0 ppm and Brassica, leafy at 14.0 ppm (established at 40 
CFR 180.418). These tolerances were established under [PP] 2F2623, 
4F2986, 3F2824, 7F3498, 4F3011, and 4F4291. 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 cypermethrin in plants is 
adequately understood. Studies have been conducted to delineate the 
metabolism of radiolabelled cypermethrin 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 cypermethrin 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).
    3. Magnitude of residues. Crop field trial residue data from 
studies conducted at the maximum label rates for cotton, pecans, head 
lettuce, bulb onions, cabbage,  Brassica, head and stem, and Brassica, 
leafy show that the established cypermethrin tolerances on cottonseed 
of 0.5 ppm, pecans 0.05 ppm, lettuce, head at 10.0 ppm, onions, bulb at 
0.10 ppm, cabbage at 2.0 ppm, Brassica, head and stem at 2.0 ppm and 
Brassica, leafy at 14.0 ppm will not be exceeded when the cypermethrin 
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 NOEL of 1.0 mg/kg/day from the chronic toxicity 
study in dogs. The LOEL of this study of 5.0 mg/kg/day was based on 
gastrointestinal disturbances observed in the first week of the study. 
This acute dietary endpoint is used to determine acute dietary risks to 
all population subgroups.
    2. Genotoxicty. The following genotoxicity tests were all negative:

[[Page 50350]]

 gene mutation (Ames); chromosome aberration in Chinese hamster bone 
marrow cells; host mediated assay in mice; dominant lethal assay in 
mice.
    3. Reproductive and developmental toxicity. No evidence of 
additional sensitivity to young rats or rabbits was observed following 
pre- or postnatal exposure to cypermethrin.
    a. A three-reproductive toxicity study in rats demonstrated a NOEL 
of 2.5 mg/kg/day and a LOEL of 7.5 mg/kg/day for parental/systemic 
toxicity based on decreased body weight gain in both sexes. There were 
no adverse effects in reproductive performance. The NOEL for 
reproductive toxicity was considered to be 37.5 mg/kg/day, the highest 
dose level tested.
    b. A developmental study in rats demonstrated a maternal NOEL of 
17.5 mg/kg/day and a LOEL of 35 mg/kg/day based on decreased body 
weight gain. There were no signs of developmental toxicity at 70 mg/kg/
day, the highest dose level tested.
    c. A developmental study in rabbits demonstrated a maternal NOEL of 
100 mg/kg/day and a LOEL of 450 mg/kg/day based on decreased body 
weight gain. There were no signs of developmental toxicity at 700 mg/
kg/day, the highest dose level tested.
    4. Subchronic toxicity. Short- and intermediate-term toxicity. The 
systemic NOEL of 5.0 mg/kg/day from the chronic toxicity study in dogs 
is also used for short- and intermediate-term MOE calculations (as well 
as acute, discussed in (1) above). This NOEL was based on neurotoxic 
clinical signs observed in the first week of treatment of the study.
    5. Chronic toxicity-- a. The RfD has been established at 0.010 mg/
kg/day. This RfD is based on a chronic toxicity study in dogs with a 
NOEL of 1.0 mg/kg/day, based on gastrointestinal disturbances observed 
at the LOEL of 5.0 mg/kg/day during the first week of the study; an 
uncertainty factor of 100 is used.
    b. Cypermethrin is classified as a Group C chemical (possible human 
carcinogen with limited evidence of carcinogenicity in animals) based 
upon limited evidence for carcinogenicity in female mice; assignment of 
a Q* has not been recommended.
    6. Animal metabolism. The metabolism of cypermethrin in animals is 
adequately understood. Cypermethrin has been shown to be rapidly 
absorbed, distributed, and excreted in rats when administered orally. 
Cypermethrin is metabolized by hydrolysis and oxidation.
    7. Metabolite toxicology. The Agency has previously determined that 
the metabolites of cypermethrin 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 cypermethrin 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 cypermethrin has an adverse effect on the 
endocrine system.

C. Aggregate Exposure

    1. Dietary exposure-- Food . Tolerances have been established for 
the residues of cypermethrin, in or on a variety of raw agricultural 
commodities. Tolerances, in support of registrations, currently exist 
for residues of cypermethrin on cottonseed; pecans; lettuce, head; 
onions, bulb; cabbage; Brassica, head and stem; Brassica, leafy and 
livestock commodities of cattle, goats, hogs, horses, and sheep. A 
pending tolerance for onions, green also exists. For the purposes of 
assessing the potential dietary exposure for these existing and pending 
tolerances, 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 one day or single exposure. For the purposes of 
assessing acute dietary risk for cypermethrin, the maternal NOEL of 1.0 
mg/kg/day from the chronic toxicity study in dogs was used. The LOEL of 
this study of 5.0 mg/kg/day was based on gastrointestinal disturbances 
observed in the first week of the study. 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 MOEs 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 0.00067 mg/kg/day (MOE of 1,493); 99th 
percentile 0.002109 mg/kg/day (MOE of 474); and 99.9th 
percentile 0.004543 mg/kg/day (MOE of 220). The 95th 
percentile of exposure for all infants < 1 year old was estimated to be 
0.000562 mg/kg/day (MOE of 1,780); 99th percentile 0.000896 
mg/kg/day (MOE of 1,116); and 99.9th percentile 0.001362 mg/
kg/day (MOE of 734). The 95th percentile of exposure for 
nursing infants < 1 year old was estimated to be 0.000213 mg/kg/day 
(MOE of 4,706 ); 99th percentile 0.000587 mg/kg/day (MOE of 
1,704); and 99.9th percentile 0.001660 mg/kg/day (MOE of 
602). The 95th percentile of exposure for non-nursing 
infants < 1 year old was estimated to be 0.000613 mg/kg/day (MOE of 
1,631); 99th percentile 0.000939 mg/kg/day (MOE of 1,065); and 
99.9th percentile 0.001224 mg/kg/day (MOE of 817). The 
95th percentile of exposure for children 1 to 6 years old 
(the most highly exposed population subgroup) was estimated to be 
0.000819 mg/kg/day (MOE of 1,221); 99th percentile 0.002400 
mg/kg/day (MOE of 417); and 99.9th percentile 0.005694 mg/
kg/day (MOE of 176). Therefore, FMC concludes that the acute dietary 
risk of cypermethrin, 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 1.0 mg/kg/day from the chronic dog study and an uncertainty 
factor of 100 is 0.010 mg/kg/day. The endpoint effect of concern were 
based on gastrointestinal disturbances observed in the first week of 
the study at the LOEL of 5.0 mg/kg/day. A chronic dietary exposure/risk 
assessment has been performed for cypermethrin 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 0.000024 mg/kg bwt/day and 
utilize 0.2% 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 0.000018 mg/kg bwt/day and 
0.000042 mg/kg bwt/day and utilizes 0.2% and 0.4% 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 cypermethrin, 
as estimated by the dietary risk assessment, does not appear to be of 
concern.
    2. Drinking water. Laboratory and field data have demonstrated that 
cypermethrin is immobile in soil and

[[Page 50351]]

will not leach into groundwater. Other data show that cypermethrin 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 
cypermethrin 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 for each product use category (indoor total release 
fogger and lawn care) and exposed population group (adults, children 1-
6 years, and infants < 1 year) are compared to the systemic absorbed 
dose No-Observed-Effects-Level (NOEL) for cypermethrin to provide 
estimates of the MOEs. Based on the toxicity endpoints selected by EPA 
for cypermethrin, 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 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 total non-dietary MOEs (combined across all product use 
categories) for the inhalation + incidental oral routes are 97,000 for 
adults, 2,100 for children 1-6 years old, and 1,900 for infants (< 1 
year). The aggregate MOE (inhalation + incidental oral + chronic 
dietary, summed across all product use categories) was estimated to be 
66,000 for adults, 2,000 for children 1-6 years old and 1,900 for 
infants (<1 year). It can be concluded that the potential non-dietary 
and aggregate (non-dietary + chronic dietary) exposures for 
cypermethrin are associated with substantial margins of safety.

D. Cumulative Effects

    In consideration of potential cumulative effects of cypermethrin 
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 cypermethrin 
would be cumulative with those of other chemical compounds; thus only 
the potential risks of cypermethrin 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 
cypermethrin consistent with the schedule established by EPA at 62 FR 
42020 (August 4, 1997) and other EPA publications pursuant to the Food 
Quality Protection Act.

E. Safety Determination

    1. U.S. population. Based on a complete and reliable toxicology 
database, the acceptable RfD is 0.010 mg/kg/day, based on a LOEL of 5.0 
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 0.000024 
mg/kg body weight (bwt)/day and utilize 0.2% 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 0.000018 mg/kg bwt/day and 0.000042 mg/kg bwt/day and utilizes 0.2% 
and 0.4% 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 
cypermethrin, 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 1,493; 474 at the 
99th percentile; and 220 at the 99.9th 
percentile. For all infants < 1 year old, the calculated MOE at the 
95th percentile was estimated to be 1,780; 1,116 at the 
99th percentile; and 734 at the 99.9th 
percentile. For nursing infants < 1 year old, the calculated MOE at the 
95th percentile was estimated to be 4,706; 1,704 at the 
99th percentile; and 602 at the 99.9th 
percentile. For non-nursing infants < 1 year old, the calculated MOE at 
the 95th percentile was estimated to be 1,631; 1,065 at the 
99th percentile; and 817 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 1,221 ; 417 at the 99th percentile; and 176 
at the 99.9th percentile. Therefore, FMC concludes that 
there is reasonable certainty that no harm will result from acute 
exposure to cypermethrin.
    2. Infants and children-- a. General. In assessing the potential 
for additional sensitivity of infants and children to residues of 
cypermethrin, FMC considered data from developmental toxicity studies 
in the rat and rabbit, and a three-reproductive study in the rat. The 
data demonstrated no indication of increased sensitivity of rats or 
rabbits to in utero and/or postnatal exposure to cypermethrin. 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.

[[Page 50352]]

 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 
database.
    b. Developmental toxicity studies. In the prenatal developmental 
toxicity studies in rats and rabbits, there was no evidence of 
developmental toxicity at the highest doses tested (70 mg/kg/day in 
rats and 700 mg/kg/day in rabbits). Decreased body weight gain was 
observed at the maternal LOEL in each study; the maternal NOEL was 
established at 17.5 mg/kg/day in rats and 100 mg/kg/day in rabbits.
    c. Reproductive toxicity study. In the three-reproduction study in 
rats, offspring toxicity (reduced mean litter weight gain) was observed 
only at the highest dietary level tested (37.5 mg/kg/day), while 
toxicity in the parental animals was observed at the lower treatment 
levels. The parental systemic NOEL was 2.5 mg/kg/day and the parental 
systemic LOEL was 7.5 mg/kg/day. There were no developmental (pup) or 
reproductive effects up to 37.5 mg/kg/day (highest dose tested).
    d. Pre- and post-natal sensitivity--i. Pre-natal. There was no 
evidence of developmental toxicity in the studies at the highest doses 
tested in the rat (70 mg/kg/day) or in the rabbit (700 mg/kg/day). 
Therefore, there is no 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 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 cypermethrin residues.

F. International Tolerances

    There are no Codex, Canadian, or Mexican residue limits for 
residues of cypermethrin in or on cotton; pecans; lettuce, head; 
onions, bulb; cabbage; Brassica, head and stem, or  Brassica, leafy. 
(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)

7. McLaughlin Gormley King Company

PP 7F4915

    EPA has received a pesticide petition (PP 7F4915) from McLaughlin 
Gormley King Company, 8810 Tenth Avenue North, Minneapolis, MN 55427, 
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 (RS)-2-Methyl-4-oxo-3-(2-
propynyl) cyclopent-2-enyl (1RS)-cis, trans-chrysanthemate (common 
name, prallethrin; trade name ETOC), a Type I synthetic 
pyrethroid in or on food commodities at 1 ppm. EPA has determined that 
the petition contains data or information regarding the elements set 
forth in section 408(d)(2) of the FFDCA; however, EPA has not fully 
evaluated the sufficiency of the submitted data at this time or whether 
the data supports granting of the petition. Additional data may be 
needed before EPA rules on the petition.

A. Residue Chemistry

    1. Analytical method. An adequate analytical method is available to 
detect residues of ETOC in or on food commodities. 
Prallethrin can be extracted from samples and analyzed by gas 
chromatography, with final electron capture detection. The method has 
been confirmed through an independent laboratory validation.
    2. Magnitude of residues. Studies were conducted to determine 
residues resulting from the application of ETOC by ULV spray 
and contact spray in a simulated feed or food processing situation, and 
in a simulated warehouse situation. No residues were detected following 
contact sprays in either situation, with the exception of a trace 
amount in a peanut sample after the tenth treatment at 4X the normal 
application rate. No residues were detected in covered commodities 
after ULV spraying of ETOC, but residues were detected in 
uncovered commodities and samples with permeable wrapping.

B. Toxicological Profile

    1. Acute toxicity. An oral dosage rat study reported Category II 
toxicity with the LD50 being 640 mg/kg for males and 460 mg/
kg for females. An acute dermal study with rats reported Category IV 
toxicity. An acute inhalation study with rats reported Category II 
toxicity with an LC50 of 0.288 mg/liter for males and 0.333 
mg/liter for females. Rabbits were tested for eye and skin irritation. 
Eye irritation was minimal (Category III) and there was no skin 
irritation (Category IV). ETOC is not a skin sensitizer, 
based on a Guinea Pig dermal sensitization study. Rats were dosed at 
30, 100, and 300 mg/kg by oral gavage to test acute neurotoxicity. 
While there was some temporary motor activity reduction, there were no 
permanent treatment-related anomalies.
    2. Genotoxicity. A bacterial reverse mutation test using Salmonella 
typhimurium and Escherichia coli indicated that ETOC was not 
mutagenic. A gene mutation assay with Chinese hamster lung cells in 
both the presence and absence of S9 metabolic activation reported no 
mutagenicity. An in vitro chromosomal aberration test reported 
clastogenic potential against Chinese hamster ovary cells (CHO-K1) in 
the presence of S9 mix. An in vivo mouse bone marrow micronucleus test 
did not induce micronuclei formation in bone marrow cells of mice. An 
in vivo/in vitro unscheduled DNA synthesis test reported no induction 
of DNA damage in rat hepatocytes in vivo.
    3. Reproductive and developmental toxicity. A range-finding study 
was conducted by administering 30, 60, 100, 300, 600, and 800/1,000 mg/
kd/day by oral gavage to rabbits on days 7 through 19 of presumed 
gestation. Significantly decreased body weights occurred in those 
rabbits receiving 300 mg/kg/day and above, food consumption decreased 
at 100 mg/kg/day and above, and deaths occurred at 300 mg/kg/day and 
above. Doses as high as 100 mg/kg/day did not produce adverse effects 
in the offspring. ETOC was then administered by oral gavage 
at doses of 10, 30, 100, and 200 mg/kg/day to rabbits on days 7 through 
19 of presumed gestation. The maternal NOAEL was 100 mg/kg/day. The 200 
mg/kg/day dosage caused reduced maternal body weight gains and reduced 
absolute and relative feed consumption values. The developmental NOAEL 
was reported as 200 mg/kg/day. ETOC is not considered a 
developmental toxin. A teratology study was conducted by administering 
10, 30, 100, and 300 mg/kg/day by oral gavage to rats on days 6-15 of 
presumed gestation. The developmental NOEL was >300 mg/kg/day and the 
developmental LOEL was not determined. Compound related maternal 
mortality was reported at 300 mg/kg/day. The maternal LOEL was 30 mg/
kg/day, as determined by increased mortality at 300 mg/kg/day levels, 
clinical signs at the 30, 100, and 300 mg/kg/day dosages, and decreased 
body weight gain and food consumption. Rats were dosed with 12.5, 25.0, 
and 50 mg/kg/day by subcutaneous injection on days 7 through 17 of 
presumed gestation. No NOEL or LOEL was established, but the occurrence 
of lumbar rib variants was significantly higher in the offspring of the 
50 mg/kg/day group than in the controls. Rabbits were dosed at 1, 3, 
and 10 mg/kg/day by subcutaneous injection on days 6 through 18 of 
presumed gestation. No effects were reported on either the dams or the 
offspring. ETOC was incorporated into the feed at 
concentrations of 120, 600, 3,000, and 6,000 ppm to evaluate the 
reproductive effects on two generations of rats. The systemic toxicity 
and reproductive toxicity NOEL's were both established at 600 ppm, and 
the LOEL's were both 3,000 ppm, respectively. There were dosage-
dependent effects on weight gains, body weights, feed consumption 
values, liver weights, and reduction of pup body weight at the 3,000 
and 6,000 ppm dose levels. There were no adverse effects on viability 
or fertility in either generation up to the 6,000 ppm level.
    4. Subchronic toxicity. A 21-day dermal toxicity rat study was 
conducted at 30, 150 and 750 mg/kg/day. The test article was considered 
a mild irritant. The dermal NOEL was 150 mg/kg/day and the systemic 
NOEL was 30 mg/kg/day. A 13-week oral mouse study was conducted at 
inclusion levels of 300, 3,000, 6,000, or 12,000 ppm. The NOEL was 
3,000 ppm, and the LOEL was 6,000 ppm. A 3-month feeding study 
incorporating 100, 300, 1,000, and 3,000 ppm into the diet of rats 
reported a NOEL of 300 ppm, and a LOEL of 1,000 ppm. EPA later 
recommended raising the NOEL to 1,000 ppm and the LOEL to 3,000 ppm. A 
3-month oral study on beagle dogs dosed at 3, 10, and 30 mg/kg/day, 
administered by capsule, reported a NOEL of 3 mg/kg/day and a LOEL of 
10 mg/kg/day. A 4-week inhalation study exposed rats to 1.01, 4.39, and 
19.6 mg/m3 of 92.0% ETOC, with median aerodynamic particle 
diameter of 3.77 to 4.89 m. The NOEL was 1.01 mg/m3 and the 
LOEL was 4.39 mg/m3.

[[Page 50356]]

    5. Chronic toxicity. A 52-week oral toxicity study was conducted on 
beagle dogs administered dosage levels of 2. 5, 5.0, 10.0 or 20.0 mg/
kg/day. The NOEL was reported at 2.5 mg/kg/day; EPA's RfD/Peer Review 
Committee later recommended 5 mg/kg/day in a DER dated June 6, 1995. 
The LOEL was 5.0 mg/kg/day based upon reduced weight gain, clinical 
signs, elevated cholesterol levels and deposition of lipofuscin in 
renal and bladder epithelium. A 106-week combined oral toxicity and 
oncogenicity study was performed on rats using dietary concentrations 
of 80, 400, and 2,000 ppm. It was determined that there was no 
carcinogenic potential in rats. The NOEL was 80 ppm, and the LOEL was 
400 ppm. There were no ophthalmologic, biochemical changes, or gross 
pathological treatment-related effects except for increased liver and 
thyroid weights in the 400 ppm and above level. An 80 week dietary 
oncogenicity study on rats with dose levels of 120, 600, 3,000 and 
6,000 ppm showed that the principal effect of ETOC was 
increased liver weights in those rats given the 3,000 to 6,000 ppm 
diet. There was no indication of any treatment related effect on the 
incidence of neoplastic findings.
    6. Animal metabolism. Solutions of (4S), (1R)-trans- and (4S), 
(1R)- cis-S-4068SF (ETOC) labeled with 14C were 
given to rats by single oral dose or subcutaneous administration at 2 
mg/kg. Both isomers were rapidly absorbed, widely distributed to 
various tissues, and then readily metabolized and excreted. Neither 
isomer was retained or accumulated in any tissues. There was no marked 
difference in metabolic fate between sexes and administration routes. 
The absorption and disposition of 14C-S-4068SF cis and trans 
isomers in rats was determined after oral administration of the 
compounds at 2 and 100 mg/kg and at 2mg/kg after 14 daily doses of the 
non-labeled compounds at the same dose level. The results indicated 
that the dose was rapidly eliminated at all dose levels. A greater 
proportion was excreted in the urine of rats receiving the trans-
compound compared to the cis-compound, indicating a greater ester 
cleavage of the trans-isomer. Concentrations of compound in tissues 
were not significantly affected by repeat doses of unlabelled compound 
and concentrations at the higher dose level were in proportion to the 
increase in dose. The greatest concentrations were detected in the 
organs responsible for excretion and metabolism (liver and kidneys). 
Concentrations in these tissues were greater in females.
    7. Endocrine effects. The standard battery of required toxicity 
studies is generally considered to be sufficient to detect any 
endocrine effects, and is complete for ETOC. No developmental 
or reproductive effects were noted. The potential for ETOC to 
produce any significant endocrine effects is considered minimal
    8. Metabolite toxicology. There is no evidence that prallethrin 
contains metabolites of toxicological concern.

C. Aggregate Exposure

    1. Dietary exposure. A chronic dietary exposure analysis was 
conducted for exposure to potential prallethrin residues in all food 
commodities that can be exposed to prallethrin by indoor ULV fogging 
treatment, crack and crevice, and hard surface applications in food-
handling establishments. Residue amounts from MGK field trials in a 
simulated warehouse situation were used in the analysis. Chronic 
dietary exposure to prallethrin has been conservatively estimated to be 
less than 1% of the RfD for all population groups.
    2. Drinking water. ETOC is presently registered only for 
indoor, non-food uses. No agricultural uses are planned for 
ETOC, so residues in drinking water are not likely to be 
present.
    3. Non-dietary exposure. Acute and short-term non-dietary exposure 
assessments were conducted to determine the non-dietary exposure risk 
of prallethrin from both registered and pending, occupational and 
residential uses. These assessments considered oral, dermal, and 
inhalation exposure to prallethrin during application and post-
application of total release aerosols, crack and crevice sprays, 
broadcast carpet/hard surface sprays, pet dipping, and indoor ULV 
fogging concentrate/contact spray. Incidental ingestion of 
ETOC residues by children's hand-to-mouth behavior was 
included in the assessment. All of the MOE's for the occupational 
setting were greater than 5,200, the residential MOE's were greater 
than 4,900, and the aggregate residential assessment was greater than 
1,400. These MOE values allow a reasonable certainty that no harm will 
occur from exposure to residues of prallethrin.

D. Cumulative Effects

    The EPA guidelines for product safety testing address noticeable 
toxic effects rather than the underlying mode of toxicity. There is 
very little information or data available to determine whether or not 
the toxic mode of action of prallethrin is sufficiently similar to 
other Type I pyrethroids to be cumulative.

E. Safety Determination

    1. U.S. population. Based on the conservative aggregate exposure 
estimates noted above and the complete and reliable toxicology database 
for prallethrin, it is safe to conclude that the aggregate exposure of 
the whole U.S. population to prallethrin will be 0.2% or less of the 
RfD of 0.05 mg/kg bw/day. Children from 1 to 6 years old may be exposed 
to a slightly higher amount of prallethrin; 0.3% of the RfD.
    Generally speaking, EPA has no concerns about exposures which are 
less than 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. It is therefore concluded that 
there is a reasonable certainty that no harm will result from aggregate 
exposure to prallethrin residues.
    2. Infants and children. Developmental toxicity studies of 
prallethrin orally administered to rats and rabbits did not demonstrate 
any pre-natal sensitivies for developing fetuses. The maternal NOEL for 
rats was 10 mg/kg/day, and the maternal NOEL for rabbits was 100 mg/kg/
day.
    A two-generation reproduction study of rats administered 
prallethrin in their feed did not reveal any treatment-related 
reproductive or developmental effects in either generation. The NOEL 
for adult rats was found to be 120 ppm while the LEL was 600 ppm. The 
NOEL for fetotoxicity was found to be 600 ppm and the LEL was 3,000 
ppm.
    Since no special sensitivities to offspring were noted in these 
studies, there is no need for an additional fold safety factor to be 
applied to risk assessments.

F. International Tolerances

    There are no international maximum residue limits established for 
prallethrin; therefore, incompatibility is not an issue. (Adam Heyward)

8. Valent U. S. A. Corporation

PP 2F4144, 3F4186, 4F4327

    EPA has received a request from Valent U. S. A. Corporation, 1333 
North California Blvd., Walnut Creek, CA 94596-8025 pursuant to section 
408(d) of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. 346a(d), 
to amend 40 CFR 180.466 to remove the time limitations on tolerances 
for residues of the pyrethroid insecticide chemical fenpropathrin, 
alpha-cyano-3-phenoxybenzyl 2,2,3,3-tetramethylcyclo-
propanecarboxylate, in or on the raw agricultural commodities 
cottonseed at 1.0 parts per million

[[Page 50357]]

(ppm), peanut nutmeat at 0.01 ppm, peanut vine hay at 20 ppm, 
strawberry at 2.0 ppm, tomato at 0.6 ppm, meat and meat by-products of 
cattle, goats, hogs, horses and sheep at 0.1 ppm, fat of cattle, goats, 
hogs, horses and sheep at 1.0 ppm, milk fat (reflecting 0.08 ppm in 
whole milk) at 2.0 ppm, and poultry meat, fat, meat by-products and 
eggs at 0.05 ppm, and in the processed products cottonseed oil at 3.0 
ppm and cottonseed soapstock at 2.0 ppm. The tolerances were first 
established in response to pesticide petitions PP 2F4144, 3F4186, and 
4F4327 and were only made time limited because of concerns associated 
with toxicity to aquatic arthropods. EPA has determined that the 
request contains data or information consistent with 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 request. Additional data may be 
needed before EPA rules on the request.

A. Residue Chemistry

    Summary. An extensive plant and animal metabolism data base 
demonstrates that the appropriate definition of aged fenpropathrin 
residue is parent. Ruminant and poultry feeding studies have shown that 
feed to residue ratios are very low in most commodities, with higher 
(but still relatively low) ratios in fat and milk fat. This section 
will describe residue data supporting the establishment of tolerances 
for residues of fenpropathrin in or on the raw agricultural commodities 
cottonseed at 1.0 parts per million (ppm), peanut nutmeat at 0.01 ppm, 
peanut vine hay at 20 ppm, strawberry at 2.0 ppm, tomato at 0.6 ppm, 
meat and meat by-products of cattle, goats, hogs, horses and sheep at 
0.1 ppm, fat of cattle, goats, hogs, horses and sheep at 1.0 ppm, milk 
fat (reflecting 0.08 ppm in whole milk) at 2.0 ppm, and poultry meat, 
fat, meat by-products and eggs at 0.05 ppm, and in the processed 
products cottonseed oil at 3.0 ppm and cottonseed soapstock at 2.0 ppm. 
The approved analytical method is capillary gas-liquid chromatography 
with flame ionization detection.
    1. Plant metabolism. The plant metabolism of fenpropathrin has been 
studied in five different crop plant species: cotton, apple, tomato, 
cabbage, and bean. Radiocarbon labeling has been in the cyclopropyl 
ring of the acid, in the aryl rings of the alcohol, and in the nitrile 
of fenpropathrin, a cyanohydrin ester. The permutations of radiocarbon 
label position and plant species yield a total of 17 separate, reviewed 
studies. Each of the studies involved foliar treatment of the plants 
under either greenhouse or field conditions and, while the actual 
treatment conditions and times to harvest varied from study to study, 
the results of the many studies are remarkably consistent. The total 
toxic residue is best defined as parent, fenpropathrin.
    Fenpropathrin remains associated with the site of application and 
only traces are found in seeds (e.g., bean or cotton) or in other parts 
of the plant not directly exposed to the application. Much of the 
parent residue can be removed from the plant material with a mild 
hexane/acetone or hexane rinse, demonstrating that the residue is 
located on or near the outside surface of the plant material. The 
primary metabolic pathway for fenpropathrin in plants is similar to 
that in mammals. There are no qualitatively unique plant metabolites; 
the primary aglycones are identical in both plants and animals.
    2. Analytical method. Adequate analytical methodology is available 
to detect and quantify fenpropathrin (and its metabolites) at residue 
levels in numerous matrices. The methods use solvent extraction and 
partition and/or column chromatography clean-up steps, followed by 
separation and quantitation using capillary column gas-liquid 
chromatography with flame ionization detection. The extraction 
efficiency has been validated using radiocarbon samples from the plant 
and animal metabolism studies. The enforcement methods have been 
validated at independent laboratories, and by EPA. The limit of 
quantitation for fenpropathrin in raw agricultural commodity samples is 
0.01 ppm.
    3. Magnitude of residues-- Cotton. The time limited section 408 
tolerance for fenpropathrin in/on cottonseed is 1.0 ppm. The use 
pattern allows a maximum single application rate of 0.3 lb ai/acre, a 
total maximum seasonal use of 0.8 lb ai/acre, and a 21-day phi. The 
field residue experiments were performed in six years at thirty-three 
sites in nine states. There were 38 separate treatments yielding 101 
separate, treated samples for analysis. The existing time limited 
tolerance of 1.0 ppm is based on all of the field residue data, 
including treatments at exaggerated rates. For the subset of the field 
residue samples that most closely match the present, labeled use 
pattern, 0.3 lb ai/acre, 5 applications, and a 21-day phi, the average 
residue was 0.069 ppm (n = 14, n-1 = 0.091). The 
highest average residue (HAR) found in these crop field trials for 
fenpropathrin in/on cottonseed was 0.28 ppm.
    There are existing time limited section 408 tolerances for 
fenpropathrin in the processed products cottonseed oil (3.0 ppm) and 
cottonseed soapstock (2.0 ppm). Three processing studies yielding 
hulls, extracted meal, crude cottonseed oil, refined cottonseed oil, 
and cottonseed soapstock were performed. These studies demonstrated 
that fenpropathrin residues were reduced in extracted meal but did 
concentrate in refined cottonseed oil (average concentration factor = 
2.77) and soapstock. Tolerances for the processed products cottonseed 
oil and cottonseed soapstock were needed because the concentration 
factors were greater than unity. Soapstocks are no longer considered 
significant feed commodities. The HAR times the average concentration 
factor for cottonseed oil (0.28 ppm x 2.77 = 0.78 ppm) is less than the 
tolerance of 1.0 ppm. Under present residue chemistry guidelines, 
tolerances for cottonseed oil and soapstock would no longer be 
required.
    The calculated mean residue value for cottonseed of 0.07 ppm was 
used in both the chronic and acute dietary exposure and risk 
assessments since cottonseed is a blended commodity. Processing factors 
used in the assessments were refined cottonseed oil (2.77), cottonseed 
meal (0.48), and cottonseed hulls (0.90).
    Peanut. The time limited section 408 tolerances for fenpropathrin 
in/on peanut nutmeat is 0.01 ppm and in/on peanut vine hay is 20.0 ppm. 
The use pattern allows a maximum single application rate of 0.3 lb ai/
acre, a total maximum seasonal use of 0.8 lb ai/acre, and a 14-day 
interval before digging the peanuts or feeding the vines or hay. The 
field residue experiments were performed in two years at seven sites in 
five states. There were 9 separate treatments yielding 22 separate, 
treated samples for analysis for nutmeats, green vines, and dried vine 
hay. Data from the subset of the field residue samples that most 
closely match the present, labeled use pattern, 0.3 lb ai/acre, 2 or 
more applications, and a 14-day phi were used to support the 
tolerances.
    Peanut nutmeats. No finite residues were detected (< 0.01 ppm) in 
17 of 18 samples. In a single sample a finite residue of .01 ppm was 
detected.
    Peanut vine hay. Field dried vines, peanuts removed, were sampled 
at 14-days plus 2- to 9-days field drying time following the last 
application. The average residue found in/on peanut vine hay was 8.31 
ppm (n = 16, n-1 = 4.64 ppm). The HAR for peanut 
vine hay was 16 ppm. A peanut processing study using a very highly 
exaggerated field

[[Page 50358]]

application rate showed positive concentration in peanut oil and other 
processed products. However, Agency guidance has indicated that no 
additional tolerances are needed.
    Except for a single sample of peanut nutmeat (0.01 ppm) all 
appropriate field trial data were non-detects. Therefore, 0.005, or 
half the limit of detection (LOD), was used for the chronic dietary 
risk assessment, and 0.01 ppm (full LOD) was used for the acute 
assessment. Calculated mean residue values were used for peanut 
commodities in both the chronic and acute assessments because peanuts 
is a blended commodity. The processing factor for deodorized bleached 
refined oil (1.33) was used in the risk assessments since this is the 
grade of peanut oil available for human consumption. For feed, the 
processing value for expeller presscake (1.33) was used for peanut 
meal.
    Strawberry. The time limited section 408 tolerance for 
fenpropathrin in/on strawberries is 2.0 ppm. The use pattern allows a 
maximum single application rate of 0.4 lb ai/acre, a minimum 30-day 
interval between treatments, a total maximum seasonal use of 0.8 lb ai/
acre, and a 2-day phi. The field residue experiments were performed in 
three years at twelve sites in six states. There were 47 separate 
treatments yielding 128 separate, treated samples for analysis. For the 
subset of the field residue samples that most closely match the 
present, labeled use pattern, 0.4 lb ai/acre, 1 or 2 applications with 
a (approximately) 30-day interval between treatments, and a 2-day phi, 
the average residue was 0.65 ppm (n = 34, n-1 = 
0.44). The HAR found in these crop field trials in/on strawberries was 
1.45 ppm.
    For chronic dietary exposure and risk assessment, the mean residue 
value (0.65 ppm) was used. For acute assessment, the complete 
distribution of the appropriate field trial data was used.
    Tomato. The time limited section 408 tolerance for fenpropathrin 
in/on tomato is 0.6 ppm. The use pattern allows a maximum single 
application rate of 0.2 lb ai/acre, a total maximum seasonal use of 0.8 
lb ai/acre, and a 3-day phi. The field residue experiments were 
performed in four years ateighteen sites in eight states. There were 27 
separate treatments yielding 118 separate, treated samples for 
analysis. For the subset of the field residue samples that most closely 
match the present, labeled use pattern, 0.2 lb ai/acre, 4 (or more) 
applications, and a 3-day phi, the average residue was 0.166 ppm (n = 
54, n-1 = 0.132). The highest average residue (HAR) 
found in these crop field trials for fenpropathrin in/on tomatoes was 
0.55 ppm.
    A tomato processing study using an exaggerated field application 
rate showed positive concentration in wet and dried tomato pomace. 
However, Agency guidance has indicated that no additional tolerances 
are needed.
    The mean residue value of 0.17 ppm was used for all tomatoes in the 
chronic dietary assessment, and for the blended commodities in the 
acute assessment (paste, puree, juice, and catsup). In the acute 
assessments, a complete distribution of the appropriate field trial 
data was used for whole and dried tomatoes. Appropriate concentration 
factors were used for processed commodities: tomato juice (0.05), 
canned tomatoes (0.08), tomato paste (0.3).
    Secondary residues. Residues in animal feed may transfer to animal 
products, meat, milk, and eggs, used in human food. The existing time 
limited tolerances are meat and meat by-products of cattle, goats, 
hogs, horses and sheep at 0.1 ppm, fat of cattle, goats, hogs, horses 
and sheep at 1.0 ppm, milk fat (reflecting 0.08 ppm in whole milk) at 
2.0 ppm, and poultry meat, fat, meat by-products and eggs at 0.05 ppm. 
The feed items that are associated with the existing registered uses 
for beef and dairy cattle are peanut hay, cottonseed, cotton gin by-
products (feeding restriction), cottonseed hulls, cottonseed meal and 
peanut meal in descending order of the magnitude of the anticipated 
residues. For poultry and swine only cottonseed and peanut meals are 
significant feed items. Tissue to feed residue ratios vary from a high 
of 0.0139 in fat to 0.001625 in milk, to a low of 0.00004 in liver in 
cattle. In poultry, tissue to feed ratios vary from a high of 0.0069 in 
fat to a low of 0.0002 in muscle. Both chronic and acute dietary 
assessments show very low residue contribution from secondary residues 
in animal products to all population sub-groups.

B. Toxicological profile

    Summary. The existing registrations and tolerances of fenpropathrin 
are supported at EPA by a complete toxicology data base. Toxicity 
endpoints of concern have been identified by the Agency's Health 
Effects Division, Hazard Identification Assessment Review Committee. 
The identified endpoints are an Acute Dietary of 6.0 mg/kg/day 
(systemic) and a Chronic Dietary of 2.5 mg/kg/day (RfD = 0.025 mg/kg/
day, UF = 100). No endpoints of concern were identified by the 
Committee for occupational or residential, dermal or inhalation 
exposures of any duration.
    1. Acute toxicity. The following acute toxicity studies using 
fenpropathrin technical as the test material have been reviewed and 
accepted by EPA to support registration.
    Acute oral, rat. The rat oral LD50 values were 
determined to be 54.0 and 48.5 milligrams per kilogram body weight (mg/
kg) for male and female rats, respectively. Toxicity Category I.
    Acute dermal, rat. The rat dermal LD50 values were 
determined to be 1600 and 870 mg/kg for male and female rats, 
respectively. Toxicity Category II.
    Acute inhalation, rat. A high dosage inhalation study is 
technically not possible because of the low vapor pressure and thick, 
viscous nature of fenpropathrin technical. The study has been waived by 
the Agency. Toxicity Category IV.
    Primary eye irritation, rabbit. No corneal involvement; mild iris 
and conjunctival irritation. Toxicity Category III.
    Primary dermal irritation, rabbit. No irritation. Toxicity Category 
IV.
    Dermal sensitization, guinea pig. Not a sensitizer.
    Acute oral and acute dermal toxicity studies have also been 
submitted on the mouse and rabbit. In the acute oral and dermal 
studies, clinical signs of toxicity included tremors, 
hyperexcitability, muscular fibrillation, ataxia of the hind limbs, 
urinary incontinence, diarrhea, and salivation. The intoxicated animals 
from the oral studies showed no major changes in tissues or organs at 
necropsy. Where there were sexual differences in toxicity, females were 
consistently slightly more sensitive than males. Surviving animals 
recovered in two days in the case of rats and mice and within 4 days in 
the case of rabbits. In surviving animals, all clinical signs were 
completely reversible.
    2. Genotoxicty. Fenpropathrin does not present a genetic hazard. 
The Agency has reviewed, accepted, and classed as negative the 
following genotoxicity tests: A gene mutation assay (Ames), a 
chromosomal aberration study in rodents, an in vitro cytogenics assay, 
a sister chromatide exchange on CHO-K1 cells, and DNA damage/repair in 
Bacillus subtilis.
    3. Reproductive and developmental toxicity. There is no evidence 
from reproduction or developmental toxicity studies that the developing 
fetus, young growing and developing animals, or adult reproducing 
animals are any more sensitive to fenpropathrin effects than mature 
adult animals. In addition, reproductive parameters were

[[Page 50359]]

unaffected at dosages higher than those that caused overt adult 
toxicity.
    Three-generation reproduction study, rats. Dietary concentrations 
of 0, 40, 120, and 360 ppm were fed continuously to rats for three 
generations to assess the effect of fenpropathrin on reproductive 
function. (Parent) Systemic no effect level (NOEL) of 40 ppm (M/F 3.0/
3.4 mg/kg/day). Systemic lowest effect level (LEL) of 120 (M/F 8.9/10.1 
mg/kg/day)--body tremors with spasmodic muscle twitches, increased 
sensitivity, and maternal lethality. Reproductive NOEL 120 ppm (M/F 
8.9/10.1 mg/kg/day). Reproductive LEL 360 ppm (M/F 26.9/32.0 mg/kg/
day)--Decreased mean F2 loss. (Pups) Developmental NOEL 40 
ppm (M/F 3.0/3.4 mg/kg/day). Developmental LEL 120 ppm (M/F 8.9/10.1 
mg/kg/day)--body tremors, increased mortality.
    Developmental toxicity, rabbits. Female rabbits were treated by 
gavage on days 7 through 19 of pregnancy with 0, 4, 12, and 36 mg/kg/
day in corn oil to assess the maternal and developmental toxicity of 
fenpropathrin. Maternal NOEL 4 mg/kg/day, maternal LEL 12 mg/kg/day 
(grooming, anorexia, flicking of the forepaws). Developmental NOEL > 36 
mg/kg/day, there were no compound-related effects on development. 
Clinical signs included grooming, anorexia, flicking of the forepaws 
and hindfeet, shaky movements, trembling, stamping of the hindfeet, and 
lethargy.
    Developmental toxicity, rats. Female rats were treated by gavage on 
days 6 through 15 of pregnancy with 0, 0.4, 1.5, 2.0, 3.0, 6.0 and 10 
mg/kg/day in corn oil to assess the maternal and developmental toxicity 
of fenpropathrin. Maternal NOEL 6 mg/kg/day, maternal LEL of 10 mg/kg/
day (death, moribundity, ataxia, sensitivity to external stimuli, 
spastic jumping, tremors, prostration, convulsion, hunched posture, 
squinted eyes, chromodacryorrhea, and lacrimation). Developmental NOEL 
> 10 mg/day. No developmental effects were observed at a dose that was 
lethally neurotoxic to 7 of 30 dams.
    4. Subchronic toxicity- Subchronic feeding, rat 3-month. 
Fenpropathrin was fed to rats at dietary concentrations of 0. 3, 30, 
100, 300 and 600 ppm. The NOEL was determined to be 300 ppm (15 mg/kg/
day). The LEL was 600 ppm (30 mg/kg/day)--body weight reduction (F), 
body tremors, reduced kaolin-cephalin clotting time (F), increased 
alkaline phosphatase and potassium (M), increased brain (F) and kidney 
(M) weights.
    Subchronic feeding, dog 3-month. Groups of six male and six female 
beagle dogs were fed diets containing 250, 500. and 750 ppm 
fenpropathrin for 13 weeks. The NOEL was not determined and is less 
than 250 ppm (7.25 mg/kg/day). At this dosage there were signs of GI 
tract disturbance (note dog chronic, below). At higher feeding levels 
the following effects were observed: 500 ppm (15 mg/kg/day) produced 
tremors and body weight loss in females, 750 ppm (22.25 mg/kg/day) 
produced tremors, ataxia and blood changes (reduced RBC, HCT, HGB).
    Dermal, rabbit 21-day. Ten rabbits of each sex at each dose, half 
with intact skin and half with abraded skin, were treated dermally with 
500, 1200 and 3000 mg/kg/day. The experimental animals were treated 5 
days per week for three weeks. There was localized dermal irritation 
but there were no systemic effects. The systemic NOEL was determined to 
be greater than 3000 mg/kg/day.
    5. Chronic toxicity. A complete chronic data base supported by 
appropriate subchronic studies for fenpropathrin is available to the 
Agency. A chronic RfD has been identified, and a safety factor of 100 
is appropriate. Fenpropathrin shows no evidence of oncogenicity at 
maximum tolerated dosages. Clinical signs of chronic toxicity were 
observed as body tremors, at high dosages with little other effects 
noted.
    Oral toxicity study, dogs 12-month. Groups of male and female 
beagle dogs were fed diets containing 0, 100, 250. and 750 ppm 
fenpropathrin for 52 weeks. Systemic NOEL of 100 ppm (2.5 milligram 
(mg)/kilogram (kg)/day) and a systemic LEL of 250 ppm (6.25 mg/kg/day).
    Chronic/carcinogenicity feeding, rat 24-month. Groups of male and 
female Charles River CD rats were fed diets containing 0, 50, 150, 450, 
and 600 ppm fenpropathrin for 104 weeks. Systemic NOEL's of 450 ppm in 
males, 150 ppm in females (17.06 mg/kg/day and 7.23 mg/kg/day, 
respectively). Systemic LEL of 600 ppm [(HDT): 22.80 mg/kg/day] in 
males (increased mortality, body tremors, increased pituitary, kidney, 
and adrenal weights), and systemic LEL of 450 ppm (19.45 mg/kg/day) in 
females (increased mortality and body tremors). There were no oncogenic 
effects observed at any dose level.
    Chronic/carcinogenicity feeding study, mouse 24-month. Groups of 
male and female Charles River (UK) CD-1 mice were fed diets containing 
0, 40, 150, and 600 ppm fenpropathrin for 104 weeks. Systemic NOEL 
greater than 600 ppm HDT (males and females; 56.0 and 65.2 mg/kg/day, 
respectively). There were no indications of toxicity or carcinogenicity 
other than marginally increased hyperactivity in females dosed at 600 
ppm.
    Carcinogenicity. Fenpropathrin has been classified in EPA Weight-
of-the Evidence Category ``Group E--Evidence of Non-Carcinogenicity for 
Humans'' for carcinogenicity by the EPA/RFD/PR committee reviewed 1/29/
93 and EPA verified 3/18/93. Studies in two species with adequate 
dosing show no evidence of oncogenicity.
    6. Animal metabolism. Acceptable rat metabolism studies have been 
performed using single high (25 mg/kg), and single and multiple low 
(2.5 mg/kg) doses using both sexes. Elimination was similar in both 
sexes. The urine: feces ratio of elimination was 1:2 following the high 
or low single dose, and 1:1 following the 15 daily doses. The half life 
was 11-16 hours in the urine, and 7-9 hours in the feces. After 7 days, 
greater than 99% of the administered dose was excreted. A small 
percentage of radiolabel was found in the tissues (primarily in the 
fat). The major biotransformations included cleavage of the ester, 
oxidation at the methyl group of the acid moiety, and hydroxylation at 
the 4'-position of the alcohol moiety. Ester cleavage products, 
2,2,3,3-tetramethylcyclopropanecarboxylic acid and (after oxidation) 3-
phenoxybenzoic acid, were excreted either directly or conjugated as 
sulfates or glucuronides. Parent was detected in the feces, but not in 
the urine. Eight urinary metabolites and 4 fecal metabolites were 
identified.
    There are no qualitatively unique plant metabolites . The primary 
aglycones are identical in both plants and animals; the only difference 
is in the nature of the conjugating moieties employed.
    7. Metabolite toxicology. The metabolism and potential toxicity of 
the small amounts of terminal plant metabolites have been tested on 
mammals. Glucoside conjugates of 3-phenoxy-benzyl alcohol and 3-
phenoxybenzoic acid, administered orally to rats, were absorbed as the 
corresponding aglycones following cleavage of the glycoside linkage in 
the gut. The free or reconjugated aglycones were rapidly and completely 
eliminated by normal metabolic pathways. The glucose conjugates of 3-
phenoxybenzyl alcohol and 3-phenoxy-benzoic acid are less toxic to mice 
than the corresponding aglycones.
    8. Endocrine disruption. No special studies to investigate the 
potential for estrogenic or other endocrine effects of fenpropathrin 
have been performed. However, as summarized above, a large

[[Page 50360]]

and detailed toxicology data base exists for the compound including 
studies acceptable to the Agency in all required categories. These 
studies include evaluations of reproduction and reproductive toxicity 
and detailed pathology and histology of endocrine organs following 
repeated or long term exposure. These studies are considered capable of 
revealing endocrine effects and no such effects were observed.

C. Aggregate Exposure

    1. Dietary exposure. Toxicity endpoints of concern have been 
identified by the Agency's Health Effects Division, Hazard 
Identification Assessment Review Committee (July 17 and 24, 1997). The 
identified endpoints are a Chronic Dietary of 2.5 mg/kg/day (RfD = 
0.025 mg/kg/day, UF = 100) and an Acute Dietary of 6.0 mg/kg/day 
(systemic). Thus, both chronic and acute exposure and risk analyses are 
necessary.
    2. Food. Chronic and acute dietary exposure analyses were performed 
for fenpropathrin using anticipated residues and accounting for 
proportion of the crop treated. The crops included in the analyses are 
cottonseed, currants, peanuts, strawberries, tomatoes, and the 
secondary residues in meat, milk, and eggs. These exposure/risk 
analyses have been submitted to the Agency along with a detailed 
description of the methodology and assumptions used.
    Chronic dietary exposure was calculated for the U.S. population and 
26 population subgroups. The results from several representative 
subgroups are listed below. In all cases, chronic dietary exposure was 
at or below 0.2 % of the reference dose and strawberries was the 
commodity contributing the most exposure.

----------------------------------------------------------------------------------------------------------------
                   Population subgroup                        Exposure (mg/kg bw/day)         Percent of RfD    
----------------------------------------------------------------------------------------------------------------
Total U.S. Population                                                0.000020                                008
                                                                                                                
Females (13+/Nursing)                                                0.000036                               0.14
                                                                                                                
Non-Hispanic other than B/W                                          0.000053                               0.21
                                                                                                                
Children (1-6 Years)                                                 0.000035                               0.14
                                                                                                                
All Infants (<1 Year Old)                                            0.000002                              0.008
                                                                                                                
Non-Nursing Infants (<1 Year Old)                                    0.000003                              0.012
----------------------------------------------------------------------------------------------------------------

    Acute dietary exposure was calculated for the U.S. population and 
five children subgroups. The calculated exposures and margins of 
exposure (MOE) for the higher exposed proportions of the subgroups are 
listed below. It should be noted that the population sizes are small at 
the lower probability exposures (e.g. 99th and 
99.9th percentiles) oftentimes leading to unrealistically 
high calculated exposures. In all cases, margins of exposure exceed 
one-hundred.

                      Calculated Acute Dietary Exposures to Fenpropathrin Residues in Food                      
----------------------------------------------------------------------------------------------------------------
                                                 99th Percentile                      99.9th Percentile         
                                     ---------------------------------------------------------------------------
         Population Subgroup           Exposure (mg/kg                       Exposure (mg/kg                    
                                           bw/day)              MOE              bw/day)              MOE       
----------------------------------------------------------------------------------------------------------------
U.S. Population                            .000682                   8,804       .002800                   2,143
                                                                                                                
Children 1-6                               .000916                   6,547       .007465                     804
                                                                                                                
Children 7-12                              .000619                   9,687       .003012                   1,992
                                                                                                                
All Infants                                .001084                   5,533       .001510                   3,974
                                                                                                                
Nursing Infants (<1)                       .000297                  20,230       .000416                  14,412
                                                                                                                
Non-Nursing Infants (<1)                   .001237                   4,851       .001572                   3,816
----------------------------------------------------------------------------------------------------------------

    3. Drinking water. Since fenpropathrin is applied outdoors to 
growing agricultural crops, the potential exists for fenpropathrin or 
its metabolites to reach ground or surface water that may be used for 
drinking water. Fenpropathrin is extremely insoluble in water (14 ppb), 
with a high octanol/water partitioning coefficient (Kow 1.19 
x 105) and a relatively short soil half-life for parent and 
environmental metabolites. The Agency has determined that it is 
unlikely that fenpropathrin or its metabolites can leach to potable 
groundwater. The residence time of fenpropathrin in surface water is 
short because of its very low water solubility and high affinity to 
bind to soil. In pond studies, fenpropathrin half-lives in the water 
column were less than 1.5 days.
    To quantify the potential small exposure from drinking water, 
screening evaluations of leaching potential of a typical pyrethroid, 
cypermethrin, were conducted using EPA's Pesticide Root Zone Model 
(PRIZM3). Based on this assessment, the potential concentrations of the 
pyrethroid in groundwater at depths of 1 to 2 meters are essentially 
zero (<< 0.001 parts per billion). Potential surface water 
concentrations for the pyrethroid were estimated using PRIZM3 coupled 
with EPA's Exposure Analysis Modeling System (EXAMS) using standard EPA 
cotton runoff and Mississippi farm pond scenarios. The maximum 
concentration predicted in the simulated pond water was 0.052 ppb. 
Using standard assumptions about body weight and water consumption, the 
chronic exposure from this drinking water would be 1.5 x 
10-6 and 5.2 x 10-6 mg/kg bw/day for adults and 
children, respectively; less than 0.02 percent of the RfD for children. 
Concentrations in actual drinking water would be much lower than the 
levels predicted in the hypothetical small stagnant farm pond modeled, 
since drinking water from surface sources receives treatment prior to 
consumption. Based on these analyses, the contribution of water to any 
the dietary risk analyses is negligible.
    4. Non-dietary exposure. Fenpropathrin, as the product TAME

[[Page 50361]]

2.4 EC Spray, is registered for professional non-food use both indoors 
and outdoors on ornamentals and non-bearing nursery fruit trees. 
Fenpropathrin has no animal health, homeowner, turf, termite, or 
industrial uses. Quantitative information concerning human exposure 
from this ornamental use is not available, but exposure to the general 
public from this use of fenpropathrin is expected to be minimal. It is 
important to note that no endpoints of concern were identified by the 
Health Effects Division, Hazard Identification Assessment Review 
Committee for occupational or residential, dermal or inhalation 
exposures of any duration. Thus, no risk assessment is needed.

D. Cumulative Effects

    Section 408(b)(2)(D)(v) requires that the Agency must consider 
``available information'' concerning the cumulative effects of a 
particular pesticide's residues and ``other substances that have a 
common mechanism of toxicity.'' ``Available information'' in this 
context include not only toxicity, chemistry, and exposure data, but 
also scientific policies and methodologies for understanding common 
mechanisms of toxicity and conducting cumulative risk assessments. For 
most pesticides, although the Agency has some information in its files 
that may turn out to be helpful in eventually determining whether a 
pesticide shares a common mechanism of toxicity with any other 
substances, EPA does not at this time have the methodologies to resolve 
the complex scientific issues concerning common mechanism of toxicity 
in a meaningful way.
    There are numerous other pesticidal compounds, pyrethroids and 
natural pyrethrins, that are structurally related to fenpropathrin and 
may have similar effects on animals. In consideration of potential 
cumulative effects of fenpropathrin and other substances that may have 
a common mechanism of toxicity, there are currently no available data 
or other reliable information indicating that any toxic effects 
produced by fenpropathrin would be cumulative with those of other 
chemical compounds. Thus, only the potential risks of fenpropathrin 
have been considered in this assessment of aggregate exposure and 
effects.
    Valent will submit information for EPA to consider concerning 
potential cumulative effects of fenpropathrin consistent with the 
schedule established by EPA at 62 FR 42020 (August 4, 1997) and other 
EPA publications pursuant to the Food Quality Protection Act.

E. Safety Determination

    The Food Quality Protection Act introduces a new standard of 
safety, a reasonable certainty of no harm. To make this determination, 
at this time the Agency should consider only the incremental risk of 
fenpropathrin in its exposure assessment. Since the potential chronic 
and acute exposures to fenpropathrin are small (<< 100% of RfD, MOE >> 
100) the provisions of the FQPA of 1996 will not be violated.
    1. U.S. population-- Chronic. Using the dietary exposure assessment 
procedures described above for fenpropathrin, chronic dietary exposure 
is minimal with all population subgroups at or below 0.2 percent of the 
RfD. Addition of the small potential chronic exposure from drinking 
water (calculated above) increases the occupancy of the RfD by only 
0.006 percent. Generally, the Agency has no cause for concern if total 
residue contribution is less than 100 percent of the RfD.
    Acute. The potential acute exposure from food to the U.S. 
population (shown above) provides an MOE greatly exceeding 100. In a 
conservative policy, the Agency has no cause for concern if total acute 
exposure calculated for the 99.9th percentile yields a MOE 
of 100 or larger.
    2. Infants and children-- Safety factor for infants and children. 
In assessing the potential for additional sensitivity of infants and 
children to residues of fenpropathrin, FFDCA section 408 provides that 
EPA shall apply an additional margin of safety, up to ten-fold, for 
added protection for infants and children in the case of threshold 
effects unless EPA determines that a different margin of safety will be 
safe for infants and children.
    The toxicological data base for evaluating pre- and post-natal 
toxicity for fenpropathrin is complete with respect to current data 
requirements. There are no special pre- or post-natal toxicity concerns 
for infants and children, based on the results of the rat and rabbit 
developmental toxicity studies or the three-generation reproductive 
toxicity study in rats. EPA HED Hazard ID Committee has concluded that 
reliable data support use of the standard 100-fold uncertainty factor 
and that an additional uncertainty factor is not needed to be further 
protective of infants and children.
    Chronic risk. Using the conservative exposure assumptions described 
above, the percentage of the RfD that will be utilized by dietary (food 
only) exposure to residues of fenpropathrin ranges from 0.14 % for 
children (1-6 years old) and 0.012% for non-nursing infants (< 1 year 
old). Addition of the small potential chronic exposure from drinking 
water (calculated above) increases the occupancy of the RfD by only 
0.02 percent. Generally, the Agency has no cause for concern if total 
residue contribution is less than 100 percent of the RfD.
    Acute. The potential acute exposure from food to populations of 
infants and children (shown above) provide MOE values greatly exceeding 
100 In a conservative policy, the Agency has no cause for concern if 
total acute exposure calculated for the 99.9th percentile 
yields a MOE of 100 or larger.
    Aggregate acute or chronic dietary exposure to various sub-
populations of children and adults demonstrate acceptable risk. Chronic 
exposures to fenpropathrin occupy considerably less than 100% of the 
RfD, and all acute MOE values exceed 100. Chronic and acute dietary 
risk to children from fenpropathrin should not be of concern. Further, 
fenpropathrin has no other uses, such as indoor pest control, homeowner 
or turf, that could lead to unique, enhanced exposures to vulnerable 
sub-groups of the population. It can be concluded that there is a 
reasonable certainty that no harm will result to any sub-group of the 
U.S. population, including infants and children, from aggregate chronic 
or acute exposure to fenpropathrin residues.

F. International Tolerances

                                          Codex Maximum Residue Limits                                          
----------------------------------------------------------------------------------------------------------------
                                                                                                                
----------------------------------------------------------------------------------------------------------------
186                                                                                                Fenpropathrin
                                                                                                                
Main uses                                                                                8 Insecticide/acaracide
                                                                                                                
JMPR                                                                                                          83
                                                                                                                
ADI                                                                                0.03 mg/kg body weight (1993)
                                                                                                                

[[Page 50362]]

                                                                                                                
Residue                                                                              Fenpropathrin (fat soluble)
----------------------------------------------------------------------------------------------------------------


----------------------------------------------------------------------------------------------------------------
                       Commodity                                                                                
-------------------------------------------------------    MRL (mg/kg)         Step         JMPR         CCPR   
             Code                        Name                                                                   
----------------------------------------------------------------------------------------------------------------
MM 0812                                    Cattle meat          0.5 (fat)            6       93                 
                                                                                                                
ML 0812                                    Cattle milk              0.1 F          6st       93                 
                                                                                                                
MO 0812                        Cattle, Edible offal of               0.05          CXL                  (1995)  
                                                                                                                
SO 0691                                    Cotton seed                  1          CXL                  (1995)  
                                                                                                                
OC 0691                         Cotton seed oil, Crude                  3          CXL                  (1995)  
                                                                                                                
VO 0440                                      Egg plant                0.2            6       93                 
                                                                                                                
PE 0112                                           Eggs           0.01 (*)          CXL                  (1995)  
                                                                                                                
VC 0425                                        Gherkin                0.2          CXL                  (1995)  
                                                                                                                
FB 0269                                         Grapes                  5            6       93                 
                                                                                                                
VO 0445                                 Peppers, Sweet                  1          CXL                  (1995)  
                                                                                                                
FP 0009                                    Pome fruits                  5          CXL                  (1995)  
                                                                                                                
PM 0110                                   Poultry meat         0.02 (fat)          CXL                  (1995)  
                                                                                                                
PO 0111                          Poultry, Edible offal                                                          
                                                    of           0.01 (*)          CXL                  (1995)  
                                                                                                                
VO 0448                                         Tomato                  1          CXL                  (1995)  
----------------------------------------------------------------------------------------------------------------

    There are small differences between the section 408 tolerances and 
the Codex MRL values for secondary residues in animal products. These 
minor differences are mainly caused by differences in the methods used 
to calculate animal feed dietary exposure. The only substantial 
difference between the US tolerance and the Codex MRL value is for 
tomatoes. The JMPR reviewer required that the MRL exceed the highest 
field residue, and rounded to unity. The EPA reviewer agreed with 
Valent that one set of field residue samples was possibly compromised 
by the presence of a high rate processing treatment nearby. High 
outliers were ignored, and the tolerance was set at 0.6 ppm. (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