EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS 

PUBLISHED IN THE FEDERAL REGISTER (1/1/2007)

EPA Registration Division contact: [BeWanda Alexander (703) 305–7460]

[BASF Corporation on behalf of Whitmire Micro-Gen Research Laboratories, Inc.]

[Insert petition number]

EPA has received a pesticide petition ([insert petition number]) from [BASF 

Corporation on behalf of Whitmire Micro-Gen Research Laboratories, Inc.], [3568 Tree 

Court Industrial Blvd., St. Louis, MO 63122-6682] 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 establishing a tolerance for residues of

[combined residues of alpha-cypermethrin and cypermethrin (including

zeta-cypermethrin)( (S)-α-cyano-3-phenoxybenzyl (1R,3R)-3-(2,2-dichlorovinyl)-2,2-

dimethylcyclopropanecarboxylate and (R)-α-cyano-3-phenoxybenzyl (1S,3S)-3-(2,2-

dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate)] in or on food/feed items (other 

than those already covered by a higher tolerance as a result of use on growing crops) in 

food/feed handling establishments where food products are held, processed or 

prepared is at 0.05 parts per million. EPA has determined that the petition contains 

data or information regarding the elements set forth in section 408 (d)(2) of FDDCA; 

however, EPA has not fully evaluated the sufficiency of the submitted data at this time 
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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.

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 or GC/ECD, HPLC-UV and LC/MS/MS 

methods are available).]
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3. Magnitude of residues. [A residue study was conducted in a simulated food handling 

establishment using a pressurized liquid aerosol formulation of alpha-cypermethrin 

0.05% to make multiple crack and crevice and spot treatments at exaggerated label 

rates. Testing matrix consisted of perishable, non-perishable and inert food service 

items. Quantitation of alpha-cypermethrin was performed using GC-ECD and HPLC-UV. 

Mean recoveries ranged from 75.9% to 108% of expected values. Potential residuetransfer routes were adequately addressed. Crack and crevice and spot treatments 

resulted in low residues [less than the limit of quantitation (LOQ)] on non-covered 

food items, except for one bread sample that returned a residue measurement of 0.01 

mg/kg (LOQ). Covered food items (items covered by plastic wrap and items placed in a 

closet cabinet) did not have measureable amounts of alpha-cypermethrin.]

B. Toxicological Profile

1. Acute toxicity. [Alpha-cypermethrin has low acute oral, dermal and 

inhalation toxicity. The oral LD50 in rats is 2000 mg/kg bw [F], the dermal LD50 is >2000 

mg/kg [M/F], and the inhalation 4-hour LC50 is >2.47 mg/L [M] and >1.07 mg/L [F]. 

Alpha-cypermethrin is not a skin sensitizer but is moderately irritating to the skin and 

had no positive effects at 48 hours for the eyes of rabbits.]

2. Genotoxicty. [Alpha-cypermethrin was negative for inducing mutations in 

both in vitro Ames and an in vitro CHO/HGPRT locus mammalian cell mutation assays. 

Alpha-cypermethrin caused no increase in the incidence of chromatid or chromosome 

aberrations or polyploidy in bone marrow cells following per os in-vivo exposure to 

Wistar rats. Similarly, alpha-cypermethrin did not increase the frequency of chromatid 

gaps, chromatid breaks or total chromatid aberrations in rat liver (RL4) cell cultures. 

Alpha-cypermethrin did not produce any detectable DNA single-strand damage using 

alkaline elution profiles of

liver DNA.

From the all available data on alpha-cypermethrin, it can be concluded that this 

compound is non-mutagenic in tests with Salmonella typhimurium, Saccharomyces 

cerevisiae, and in-vivo and in-vitro tests with rat liver cells for the induction of 
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chromosome aberration and production of DNA single-strand damage. Overall, the 

weight of the evidence demonstrates that alpha-cypermethrin is not genotoxic.]

3. Reproductive and developmental toxicity. [The reproductive and 

developmental toxicity of alpha-cypermethrin was investigated in a 2-generation rat 

reproduction study as well as in rat and rabbit developmental toxicity studies. The test 

substance in these studies was either alpha-cypermethrin or zeta-cypermethrin – the 

same racemic pyrethroid mixture with similar enantiomeric composition. 

In the rat multi-generation study conducted with zeta-cypermethrin, another related 

pyrethroid racemic mixture, the test substance was administered via diet at levels of 

0, 7.5, 25, 100, 375 or 750 ppm, equivalent to 0, 0.5, 1.8, 7, 27 or 45 mg/kg/day. 

Clinical signs of neurotoxicity and isolated incidences of mortality were observed in 

the parental animals at the top dose of 45 mg/kg/day. An increased incidence of pup 

mortality was also seen at 45 mg/kg/day. At 27 mg/kg/day, decreased body weight 

gain, especially during lactation, and increased relative brain weights were observed 

in male and female adult animals. Decreased body weight gain during lactation was 

also seen among offspring at 27 mg/kg/day. The NOAEL for parental and systemic 

toxicity was 100 ppm, equivalent to 7 mg/kg body weight per day. Similarly, the 

NOAEL for offspring toxicity was 100 ppm, equivalent to 7 mg/kg/day.

Developmental toxicity studies, via gavage exposures, were conducted in rats and 

rabbits with alpha-cypermethrin. In these studies, there was no evidence of 

teratogenicity in animals treated during the phase of organogenesis.

In rabbits (0, 3, 15 or 30 mg/kg/day via gavage in corn oil vehicle), reduced maternal 

food consumption and body weights were observed at 30 mg/kg/day; no treatment 

related effects on fetal weights were observed. The NOAEL for maternal toxicity and 

embryotoxicity was 15 mg/kg/day and 30 mg/kg/day, respectively. There were no 

indications for teratogenicity.
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Administration of alpha-cypermthrin via gavage at 0, 3, 9, or 18 mg/kg/day to 

pregnant rats during fetal organogenesis (gestational days 6-15) elicited maternal 

toxicity at the two top doses, characterized by changes in clinical conditions and 

reduction in food consumption and body weight gain. Due to marked clinical signs of 

toxicity the dose level of 18 mg/kg/ day was lowered to 15 mg/kg/day on day 10 of 

gestation. Females at 18 or 15 mg/kg/day showed unsteady gait, piloerection, and 

other signs of maternal toxicity. Slight body weight reductions were also seen in the 

females at 9 mg/kg/day. A slight reduction in fetal weights was observed at these 

dose levels (9, 15/18 mg/kg/day) in concert with maternal toxicity. There was no 

indication for teratogenicity. The NOAEL for maternal and fetal toxicity was 9 

mg/kg/day.

In the rat developmental toxicity study, the maternal and developmental NOAEL was 

9 mg/kg/day. For rabbits, the NOAEL for systemic toxicity was 15 mg/kg/day, and the 

NOAEL for developmental toxicity was mg/kg/day, the highest dose tested.]

4. Subchronic toxicity. [A similar toxicity profile was observed across rats, mice 

and dogs following subchronic exposure to alpha-cypermethrin. These profiles are 

mostly related to the mode of action of alpha-cypermethrin and include effects on the 

neuromuscular system. Typical indicator effects for this mode of action were observed 

and included tremors, gait abnormalities, decreased motor activity and increased 

salivation. Surviving animals recovered within 3 -7 days. The short term and reversible 

nature of these neurotoxic effects is in line with studies showing that type II 

pyrethroids such as alpha-cypermethrin can cause exaggerated pharmacological 

effects at high dose levels that do not result in histopathologic lesions on nervous 

system tissues.
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In rats, clinical signs characteristic for pyrethroid neurotoxicity were observed in 

short-term toxicity studies (4-6 weeks) at ≥800 ppm. Clinical signs were more 

pronounced in males and included high stepping, splayed gait, abasia and 

hypersensitivity. Further observed effects comprised decreased food intake and body 

weights, and some hematological findings at ≥400 ppm. The NOEL was 200 ppm, 

equivalent to 10 mg/kg/day. After dietary administration at 540 ppm for 90 days, 

abnormal gait with splayed hind limbs in male rats and decreased food intake and 

body weights were observed. No other treatment-related effects occurred during the 

course of this study. The NOEL was 60 ppm, equivalent to 3 mg/kg/day.

In mice, clinical signs of toxicity including abnormal gait were also observed after

dietary administration of alpha-cypermethrin at ≥800 ppm for 4 weeks. The death of 

two animals and neurological signs of toxicity were associated with administration of 

alpha-cypermethrin at 1200 or 1600 ppm. The NOEL was 400 ppm, equivalent to 57 

mg/kg/day. In a 90-day dietary exposure toxicity study in mice, un-groomed coat, hair 

loss and encrustations on the dorsal surface, reduced body weights, and increased 

aspartate aminotransferase activity were observed at 250 ppm. The NOEL was <50 

ppm, equivalent to <7.1 mg/kg/day, based on hair loss seen at the lowest dose tested.

In dogs, clinical signs including body tremors, head nodding, ataxia, agitation, lip 

licking, subdued behavior and high stepping gait were observed at the top dose level 

(270 ppm) of a 90-day dietary toxicity study. No other treatment-related effects were 

observed after administration of alpha-cypermethrin to dogs. The NOEL was 90 ppm, 

equivalent to 2.25 mg/kg/day.]

5. Chronic toxicity. [The results of long-term oral exposure studies indicate that 

alpha-cypermethrin is not carcinogenic in mice or rats. At high doses in long term oral 

exposure studies with rats, mice and dogs, observations demonstrate evidence of 

slight neurologic signs and decreased body weight gains. This is consistent with the 

mechanism of action of alpha-cypermethrin on the peripheral and central nervous 

system, through interactions with sodium channels. The NOAEL in the mouse 

oncogenicity study was 30 ppm, equivalent to 3 mg/kg body weight/day in males and 

3.5 mg/kg body weight/day in females. In the rat chronic/oncogenicity study, the 

NOAEL was 100 ppm, equivalent to 5 mg/kg body weight/day in males and females. In 
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a chronic (1-year) dog study, the NOAEL was 60 ppm, equivalent to 2 mg/kg/day in 

males and 2.2 mg/kg/day in females.]

6. Animal metabolism. [The metabolism of cypermethrin in animals is 

adequately understood. Cypermethrin is rapidly absorbed, distributed, and excreted 

in rats when administered orally. Biotransformation is principally governed by 

hydrolytic and oxidation reactions.]

7. Metabolite toxicology. [No metabolites of toxicological concern were 

identified with alpha-cypermethrin.]
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8. Endocrine disruption. [No specific tests have been conducted with alphacypermethrin to determine whether the chemical may have an effect in humans that 

is similar to an effect produced by a naturally occurring estrogen or other endocrine 

effects. However, there were no significant findings in other relevant toxicity studies 

(e.g., sub-chronic and chronic toxicity, developmental toxicity and multi-generation 

reproductive studies) which would suggest that alpha-cypermethrin produces any 

endocrine disruption.]

C. Aggregate Exposure

1. Dietary exposure. [The acute and chronic dietary exposure assessment for 

alpha-cypermethrin was determined with the Dietary Exposure Evaluation Model 

software with Food Commodity Intake Database (DEEM-FCIDTM), version 2.16, from 

Exponent, Inc. The analysis included established tolerances for alpha-cypermethrin 

and the proposed food/feed handling establishments tolerances. Both the acute and 

chronic exposure estimates are within the EPA’s level of concern; therefore, the 

aggregate acute and chronic dietary exposure of alpha-cypermethrin, including the 

contribution of drinking water, meets the standard of reasonable certainty of no 

harm. ]

i. Food. [The aPAD for cypermethrin is based on a

NOAEL of 10 mg/kg bw/day with a 100x uncertainty factor and a 1x FQPA SF to give a 

aPAD of 0.1 mg/kg bw/day. The aPAD for alpha-cypermethrin is based on a NOAEL of 

4 mg/kg bw/day with a 100x uncertainty factor and a 1x FQPA SF to

give a aPAD of 0.04 mg/kg bw/day. The results of dietary expousre analysis show that 

the estimated food exposures are well below the Agency's level of concern (< 100% 

aPAD).]

ii. Drinking water. [Alpha-cypermethrin registration cites all the environmental 

fate studies done for the registration of zeta-cypermethrin and cypermethrin. 

Therefore, the drinking water assessment conducted for the zeta-cypermethrin 

assessment is used for this alpha-cypermethrin exposure assessment. The results of 
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drinking water analysis show that the estimated exposures are well below the 

Agency's level of concern. 

2. Non-dietary exposure. [There are no levels of concern which are exceeded 

from the residential uses.]

D. Cumulative Effects

[Alpha-cypermethrin is a member of the pyrethroid class of pesticides. 

Although all pyrethroids alter nerve function by modifying the normal biochemistry 

and physiology of nerve membrane sodium channels, EPA is not currently following a 

cumulative risk approach based on a common mechanism of toxicity for the

pyrethroids.
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E. Safety Determination

1. U.S. population. [BASF concludes that there is a reasonable certainty that no 

harm will result to the general population from the aggregate exposure to alphacypermethrin from the proposed uses.]

2. Infants and children. [BASF concludes that there is a reasonable certainty 

that no harm will result to infants or children from the aggregate exposure to Alphacypermethrin from the proposed uses.]

F. International Tolerances

[There are CODEX maximum residue levels established for cypermethrin

residues in many different crop and crop groups. JMPR considered the residue

trials for alpha-cypermethrin, zeta-cypermethrin and cypermethrin collectively.

Codex maximum residue levels have been established in the following crops:

Leafy vegetables 0.7 Edible offal, mammalian 0.05

Pome fruits 0.7 Meat, from mammals 2.0

Stone fruits 2.0 Poultry meat 0.05

Roots and tubers 0.01 Eggs 0.01

Fruiting vegetables, cucurbits 0.07 Milks 0.05

Legume vegetables 0.7 Milk fats 0.5

Pulses 0.05

Dry bean 0.05

Brassica 1.0

Leafy vegetables 0.7

Citrus fruits 2.0

Cereal grains 0.3

Corn, sweet 0.05

Oilseed 0.1

Eggplant 0.03
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Okra 0.5

Onion bulb 0.01

Bell pepper 0.1

Non-bell pepper 2.0

Pimentos 0.1

Sugar beet 0.1

Sugar cane 0.2

Tomato 0.2]