**EPA Registration**  **Division contact: [**  **BeWanda Alexander ,**  **Insecticide Branch, 703**  **-**

**305 -**  **7 460**  **] [**  **BASF Corporation ]**  **[ EPA**  **- HQ**  **- OPP**  **- 2010**  **- 0234**  **]** EPA has received a pesticide petition **0F7690** from **[ BASF Corporation**  **] ,**  **[ 26**  **Davis Drive,**  **P.O. Box 13528, Research Triangle Park, North Carolina 27709**  **- 3528**  **]** 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 e stablishing a tolerance for residues of **co mbined 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**  **- dimethylcy**  **clopropanecarboxylate )]**  in or on the raw agricultural commodity **[ tree nuts (group 14), dried shelled pea and bean, except soybean**  **(subgroup 6C), corn grain, pop corn, sweet corn, soybeans and sugar beet roots ]**  at **[ 0.05**  **]** parts per million (ppm) and commodity **[ succulent shelled pea and bean**  **(subgroup 6B) and root and tuber**  **vegetable s (group 1)**  **]** at **[0.1]** parts per million (ppm) and commodity **[ cucurbit vegetables (group 9), fruiting vegetables (group 8),**  **sugar beet tops and wheat grain ]**  at **[0.2]** parts per milli on (ppm) and commodity **[ citrus fruit (group 10**  **]** at **[ 0.35**  **]** parts per million (ppm) and commodity **[cottonseed, edible podded legume vegetable (subgroup 6A) and sorghum grain]**  at **[0.5]** parts per million (ppm) and commodity **[rice grain]** at **[1.5]** parts per mill ion (ppm). and commodity **[citrus dried pulp]** at **[1.8]** parts per million (ppm) and commodity **[ head**  **and stem brassica (subgroup 5A) ]**  at **[ 2.0**  **]** parts per million (ppm) and commodity **[citrus oil]** at **[4.0]** parts per million (ppm) and commodity **[leafy vegetable, except**  **brassica (group 4)]** at **[10]** parts per million (ppm) and commodity **[alfalfa hay]** at **[15]** parts per million (ppm)... EPA has determined that the petition contains data or information regarding the elements set forth in section 408 (d)(2) of FDDCA; h owever, 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. **Cypermethrin is a pyrethroid insecticide consist ing of three asymmetric carbon**  **atoms, and therefore, 8 stereo -**  **isomeric mixtures. Cypermethrin is also characterized as consisting of cis**  **- and trans**  **- configured diastereo**  **- isomeric**  **components based on orientation around its cyclopropane ring. Zeta -**  **cypermeth rin**  **and alpha -**  **cypermethrin are optimized stereo -**  **isomeric mixtures of cypermethrin, each consisting of**  **4 major components. These zeta**  **- cypermethrin and alpha**  **** **cypermethrin components are the enriched trans -**  **(alpha -**  **S) and cis (cis2 -** **R) isomeric orientations of**  **cypermethrin, respectively.**2

A. Residue Chemistry 1. Plant metabolism

. **[ The metabolism of cypermethrin in plants is adequately**  **understood. Studies that**  **have been conducted to determine**  **the metabolism of radiolabelled cypermethrin in various crops a** **ll produced**  **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**  **moni toring of food with residues at or above the levels set in these tolerances (Gas**  **Chromatography with Electron Capture Detection or**  **GC/ECD and**  **LC/MS/MS methods are available** **) .]** 

3. Magnitude of residues. **[ Alpha**  **- cypermethrin registration will cite the**  **ap plicable magnitude of the residue studies conducted for the registration of zeta** **** **cypermethrin. Field trials**  **with zeta -**  **cypermethrin were carried out to determine**  **the magnitude of the residue i n/on**  **root and tuber vegetables (group 1), leafy vegetables (grou**  **p 4), head and stem brassica (subgroup 5A), edible podded legume vegetable (subgroup 6A), succulent shelled pea and bean (subgroup 6B), dried**  **shelled pea and bean (subgroup 6C), fruiting vegetables (group 8), cucurbit vegetables (group 9), citrus fruit (gr**  **oup 10), tree nuts (group 14), field corn, pop**  **corn, sweet corn, wheat grain, rice grain, sorghum,**  **sugar beets, soybeans, cotton and**  **alfalfa .**  **The number and locations of field trials are in accordance with OPPTS Guideline 860.1500. Field trials were carrie**  **d out using the maximum label rates, the maximum number of applications, and the minimum pre**  **- harvest interval (PHI) for**  **all the crops. Detected residues of cypermethrin**  **in all crops support the proposed tolerances.**  **]** B. Toxicological Profile 1. Acute toxicity. **[ Acute toxicity studies conducted with**  **alpha -**  **cypermethrin show a low toxicity via the oral (category III), dermal (category III) and inhalation**  **(category IV) exposure routes. A** **lpha -**  **cypermethrin is not irritating to the eyes and**  **is not a skin sensitizer. However, it is mildly irritating to the skin. The acute**  **toxicity of alpha**  **- cypermethrin**  **EC formulation is attenuated following acute exposures via inhalation and dermal routes. The EC formulation is a skin and eye**  **irritant, mild skin sensiti zer and has moderate toxicity via oral exposure route.**  **]** 2. Genotoxicty. **[ A** **lpha -**  **cypermethrin was negative for inducing mutations in both in**  **vitro Ames and an in vitro CHO/HGPRT locus mammalian cell mutation assays. A** **lpha**   ** cypermethrin** **caused no incre ase in the incidence of chromatid or chromosome aberrations**  **or polyploidy in bone marrow cells following per os in -** **vivo exposure to Wistar rats. Similarly,**  **A lpha**  **- cypermethrin**  **did not increase the frequency of chromatid gaps, chromatid breaks or total chro**  **ma tid aberrations in rat liver (RL4) cell cultures.**  **A lpha**  **- cypermethrin** 3

**did not produce any detectable DNA single -**  **strand damage using alkaline elution profiles of liver DNA.**  **From the all available data on a** **lpha -**  **cypermethrin , it can be concluded that th**  **is 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 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 multigeneration**  **study conducted w**  **ith zeta**  **- cypermethrin,**  **another related**  **pyrethroid racemate**  **mixture, t**  **he 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**  **i ncidences**  **of mortality**  **were observed**  **in the parental animals at the top dose of 45 mg/kg/day. An increased incidence of pup**  **mo rtality**  **was also**  **seen at**  **45 mg/kg/day.**  **A t**  **27 mg/kg/day,**  **decreased body**  **weight gain, especially during lactation, and increased r**  **elative 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. T**  **he NO**  **A EL**  **for parental**  **and systemic**  **toxicity was**  **100 ppm,**  **equivalent to**  **7 mg/kg**  **body weight**  **p er**  **day. S**  **imilarly, 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 tera** **togenicity 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. Administration of**  **alpha -**  **cypermethrin via gavage at**  **0, 3, 9, or 18 mg/kg/day to**  **preg nant r**  **ats during fetal organogenesis (gestational days 6 -**  **15) e licited 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 t he dose level of 18 mg/kg** **/ da** **y 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 a** **t 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**4

**indication for teratogenicity. The NO A** **EL for maternal and fetal toxicity was 9 mg/kg** **/ day**  **. In the rat develo**  **pm ental 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 30 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 a** **lpha -**  **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 e ffects 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. In rats, c** **linical signs c haracteristic for pyrethroid neurotoxicity were observed in**  **short -**  **ter m 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 co**  **mp rised decreased food intake and**  **body weights, and some hematologica l 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 dec**  **reased 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, c** **linical signs of toxicity including abnormal gait were also observed after**  **dietary administration of alpha -**  **cypermethrin at ≥8**  **00 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, e quivalent to <7.1 mg/kg/day, based on hair**  **loss seen at the lowest dose tested. In dogs, c**  **linical 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**  **- da** **y 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

**The neurotoxic potential of alpha**  **- cypermethrin**  **was studied fo llowing**  **acute oral exposure in the rat. The subchronic neurotoxicity potential of**  **alpha -**  **cypermethrin was also investigated in the rat, using zeta** **- cypermethrin as a surrogate test**  **ma terial.**  **In the acute neurotoxicity**  **study, no deaths or adverse clinical o r pathological**  **treatment -**  **related effects were observed after oral administration of alpha**   ** cypermethrin at 4 mg/kg body weight. At 20 and 40 mg/kg body weight, clinical** **signs of neurotoxicity (including abnormal gait, piloerection, hunched posture, and diar**  **rhea), and significant differences to the controls in functional observation battery tests were observed, with females exhibiting reduced susceptibility.**  **The NOEL was 4 mg/kg.**  **No evidence of increased**  **neurotoxicity was observed in the subchronic neurotox icity**  **study with zeta**  **- cypermethrin**  **. Clinical signs of toxicity were similar to acute**  **exposure and included decreased motor activity, decreased body weight gains and food consumption. The NOAEL was 5 and 31 mg/kg/day in males and females,**  **respectively. Ov**  **erall, the neurotoxic effects elicited by**  **alpha -**  **cypermethrin were**  **reversible .**  **]**

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 or**  **al 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 w**  **as 30 ppm**  **, equivalent to 3 mg/kg b**  **ody 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, equiv alent to 5**  **mg/kg b ody**  **weight /day in**  **males and females**  **. In 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**  **adequ ately understood. Cypermethrin**  **is rapidly absorbed, distributed, and**  **excreted in rats when administered orally. Biotransformation is principally**  **governed by hydrolytic and oxidation rea**  **ction s**  **. ]**  7. Metabolite toxicology **[ No metabolites of toxicologi**  **cal concern were identified**  **with alpha -**  **cypermethrin. ]**  8. Endocrine disruption

. **[ No specific test**  **s have been conducted with alpha**  **** **cypermethrin to determine whether the chemical may have an effect in humans that**  **is similar to an effect produced by a nat urally 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** 6

**reproductive studies) which would sug gest that**  **alpha -**  **cypermethrin produces any**  **endocrine disruption. ]** 

C. Aggregate Exposure 1. Dietary exposure. **[ Exposure assessments were conducted to evaluate the**  **potential risk due to acute and chronic dietary exposure of the U.S. population and**  **su b**  **- populations**  **to residues of Alpha**  **- Cypermethrin**  **. Alpha**  **- cypermethrin is an**  **isomer of cypermethrin. Zeta -**  **cypermethrin is also an isomer of cypermethrin. When the EPA conducted the risk assessment for zeta**  **- cypermethrin (November 27,**  **2007 , D335224, Dennis**  **M cNeilly** **), EPA included all uses for**  **cypermethrin and zeta****** **cypermethrin together in the exposure and**  **risk assessment because of the close similarity in toxicity and chemical characteristics.**  **The EPA exposure and risk assessment for alpha**  **- cypermethrin wil** **l be approached similarly and the exposure assessment and risk evaluation will include**  **the uses from all three active ingredients**  **(cypermethrin, zeta -**  **cypermethrin, alpha -**  **cypermethrin). Alpha**  **- cypermethrin will**  **not be registered on any crops where zeta -**  **cype rmethrin or cypermethrin are not**  **currently registered. However, alpha -**  **cypermethrin will not be registered on all the current crops registered with zeta**  **- cypermethrin or cypermethrin.**  **Also, t he**  **application rate and seasonal maximum rate for alpha -**  **cypermeth rin will be less**  **than cypermethrin and zeta -**  **cypermethrin. Th**  **is analysis include**  **s all the**  **current existing tolerances for cypermethrin/zeta** **- cypermethrin 40 CFR 180.418**  **. ]**  i. Food. **[**

**. Acute Dietary Exposure Assessment**  **The EPA conducted a highly refine d probabilistic acute dietary exposure assessment**  **in the “Reregistration Eligibility Decision for Cypermethrin (revised 01/14/2008)” using PDP data, percent crop treated information and processing factors. This**  **refined acute d ietary exposure estimates**  **are applicable to alpha**  **- cypermethrin. The**  **only difference between alpha -**  **cypermethrin and cypermethrin are in the acute population adjusted dose (aPAD). The aPAD for cypermethrin is based on a**  **NOAEL of 10 mg/kg bw/day with a 100x uncertainty factor and a 1x FQ**  **PA 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.**  **In the cypermethrin assessment, the most highly expos ed population subgroup was**  **children 1 -**  **2 years old at 6.1% of the aPAD at the 99.9 th**  **percentile of exposure. The aPAD for cypermethrin is 0.1 mg/kg bw/day**  **and a n**  **exposure of 6.1% aPAD is a**  **food exposure of 0.0061 mg/kg bw/day . Using the same**  **acute food e**  **xposure for alpha**  **- cypermethrin, the most highly exposed population subgroup was children 1**  **- 2**  **years old at 15.3 % of the aPAD at the 99.9 th**  **percentile of exposure. The result**  **s of the analysis show that**  **the estimated food**  **exposures are well below the Agen cy's**  **level of concern (< 100% aPAD).**7

**Chronic Dietary Exposure Assessment The**  **c hronic dietary exposure estimates**  **cited in this document are from the most recent dietary assessment conducted**  **for zeta -**  **cypermethrin/cypermethrin by EPA**  **(November 5, 2007, D33 5224, Dennis McNeilly).**  **In this dietary assessment, EPA used anticipated residues, crop treated factors, residue data from PDP. For**  **commodities without a registered use or tolerance for cypermethrin/zeta**   ** cypermethrin, EPA assumed these commodities would** **be treated in a food handling establishment (100% treated) and an anticipated residues of 1⁄2 the LOD (0.05 ppm)**  **was assumed for all these commodities. Alpha**  **- cypermethrin registration will cite 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 c**  **hronic surface water value used in**  **this assessment is 0.013 ppb**  **(February 8, 2007, D334937, J. Melendez) .**  **The chronic Population Adjusted Dose (cPAD) used for U.S. population and all sub**   ** populations is 0.0** **15 mg/kg bw/day. This endpoint is based on the NOAEL value of**  **1.5 using a FQPA safety factor of 1. The most high**  **ly expos ed**  **population sub -**  **group was children 1**  **- 2 years of age which utilized**  **10.0 % cPAD. The results of the**  **chronic dietary assessment are presented in Table 1**  **. Table**  **1 .**  **Results for**  **Alpha -**  **Cypermethrin Chronic**  **Dietary Exposure**  **Analysis including Food an**  **d Drinking Water Exposure.**

**Population Exposure Estimate**  **%cPAD Subgroups**  **(mg/kg b.w./day)** U.S. Population **0.000454 3.0**  All Infants (< 1 ye ar old) **0.000943 6.3**  Children (1

- 2 years old) **0.001496 10.0**  Children (3

- 5 years old) **0.001176 7.8**  Children (6

- 12 years old) **0.00063 4.2**  Youth (13

- 19 years old) **0.000286 1.9**  Adults (20

- 49 years old) **0.000333 2.2**  Adults (50+ years old) **0.000415 2.8**  Females (13

- 49 years old) **0.000344 2.3**  **The results of the analysis show that for all populations, the exposures are below a**  **level of concern (< 100% cPAD). ]**  ii. Drinking water

.8

**[ Alpha**  **- cypermethrin will not be registered on any crops where zeta** **- cypermethrin**  **or cypermethrin are not currently registered. However, alpha -**  **cypermethrin will not be registered on all th**  **e current crops registered with zeta -**  **cypermethrin or cypermethrin.**  **Alpha -**  **cypermethrin registration will cite all the environmental fate studies done for the registration of zeta** **- cypermethrin and cypermethrin. Therefore, the drinking**  **water assessment co nducted for the zeta**  **- cypermethrin assessment is used for this**  **alpha -**  **cypermethrin exposure assessment. The acute surface water value used in this assessment is 1.0 ppb (February 8, 2007, D334937, J. Melendez).**  **The chronic surface water value used in t**  **his assessment is 0.013 ppb (February 8, 2007, D334937, J. Melendez).**  **The acute and chronic groundwater E DWC**  **value is 0.0036 ppb (February 8, 2007, D334937, J. Melendez).**  **Acute Aggregate Exposure and Risk (food and water) The aggregate acute risk inclu**  **d ing**  **exposure of Alpha**  **- Cypermethrin**  **from food and water**  **are done for the most highly exposure subpopulation, children 1**  **- 2 years old.**  **The food exposure is 0.0061 mg/kgbw/day and the drinking water exposure using a EDWC of 1.00 ppb is**  **0.000199 mg/kg bw/day The combined exposure is**  **0.006299 mg/kgbw/day which accounts for**  **15.7 % of the aPAD. T**  **he results demonstrate that there are no safety concerns for any subpopulation based on the proposed uses and**  **the results meet the FQPA standard of reasonable certainty of no harm.** 

**Short -**  **and Intermediate -**  **Term Aggregate Exposure and Risk (food, water, and residential)**  **Short -**  **and intermediate -**  **term aggregate risk assessments include**  **chronic exposure**  **from food, water, and exposure from**  **residential uses. The exposure v**  **alues used in this aggregate assessment are from the recent human health assessment for Zeta**  **** **cypermethrin conducted by EPA (D. McNally, November 27, 2007, D344749). BASF will cite the data from zeta**  **- cypermethrin for the alpha**  **- cypermethrin**  **registration. T he short** **- and intermediate**  **- term endpoint is 7.4 mg/kg bw/day. The**  **aggregate assessment was conducted for the most highly exposure population group, children 1**  **- 2 years old. The highest residential oral exposure for children 1**  **- 2 was**  **for hand -**  **to -**  **mouth activ ity from indoor**  **surfaces following crack and crevice treatment. This is the highest residential oral exposure so it is protective for all**  **other scenarios. The highest dermal residential exposure for children 1 -**  **2 years old occurred from the indoor treatme**  **nt of hard wood and carpets. This dermal exposure is protective for all other scenarios. The short** **- and intermediate**  **- term**  **aggregate exposure for children 1 -**  **2 is shown in Table 2. Table 2. Aggregate Short** **- and Intermediate**  **- term Aggregate Exposure for**  **Children 1**  **- 2 years old.** 

**Food exposure**  **MOE Oral** 

**carpet MOE**  **Dermal**

**Carpet MOE**  **Aggregate**

**MOE**9 **(mg/kg bw/day)**  **(mg/kg**

**bw/day) (mg/kg** 

**bw/day)** 0.001496 4947 0.01111 666 0.0336 220 160

**The assessment shows that the short -**  **and intermediate -** **term aggregate expo sure is**  **below the EPA level of concern. Chronic Aggregate Exposure and Risk (food and water)**  **The aggregate chronic risk includ ing e**  **xposure of Alpha**  **- Cypermethrin**  **from food and water**  **are shown in Table 1**  **. The results demonstrate there are no safety con**  **cerns for any subpopulation based on the proposed uses and the results meet the FQ**  **PA standard of reasonable certainty of no harm. ]**  2. Non

- dietary exposure

. **[ The**  **residential exposure cited in this assessment is based on the most recent exposure assess**  **ment cited for cypermethrin / zeta****** **cypermethrin (D. McNally, November 27, 2007, D344749). The residential post****** **application incidental oral exposure MOE’s range from 190 to 960,000 which exceed the target MOE of 100 (D334263; Nov. 29, 2006, Zeta**  **- cypermeth**  **rin: Revised Human Health risk assessment** **) .**  **The combined exposure to toddlers following home lawn application, hand to mouth, object to mouth, and incidental soil**  **ingestion was 2,600 which greatly exceeds the target MOE. The dermal exposure for adults is**  **not assessed because there is no dermal NOAEL selected for adults. The dermal exposure for toddlers was determined and the calculated MOEs were all**  **greater than the target MOE (D. McNally, November 27, 2007, D344749). This assessment shows that there ar**  **e no levels of concern which are exceeded from the residential uses**  **. ]**  D. Cumulative Effects **[ "Section 408(b)(2)(D)(v) requires that, when considering whether to**  **establish, modify, or revoke a tolerance, the Agency consider “available information'' c**  **oncerning the cumulative effects of a particular pesticide's residues and “other substances that have a common mechanism of toxicity."**  **Alpha**   ** cypermethrin is a member of the pyrethroid class** **of pesticides. Although all pyrethroids alter nerve function by**  **mo difying 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. Although all pyrethroids interact with sodium channels**  **, there are multiple types of sodium channels and it is currently unknown whether**  **the p**  **yrethroids have similar effects on all channels. Nor do we have a clear**  **u nderstanding of effects on key downstream neuronal function**  **e.g., nerve excitability, nor do we**  **understand how these key events interact to produce their**  **compound -**  **specific patterns of neurotoxicity. There is ongoing research by the**  **EPA's Office of Research and Development and pyrethroid registrants to evaluate** 10

**the differential biochemical and physio**  **logical actions of pyrethroids in mammals. When**  **available, the Agency will consider this research and make a determination of**  **common mechanism as a basis for assessing cumulative risk.**  **]** E. Safety Determination 1. U.S. population. **[ Based on this ris**  **k assessment, BASF concludes that there is a reasonable certainty that no harm will result to the general population from the**  **aggregate exposure to Alpha**  **- cypermethrin**  **from the proposed uses. ]**  2. Infants and children

. **[ Based on this risk assessment, BAS**  **F concludes that**  **there is a reasonable certainty that no harm will result to infants or children from the aggregate exposure to**  **Alpha -**  **cypermethrin 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**  **Po me 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 Okra**  **0.5 Onion bulb**  **0.01 Bell pepp**  **er 0.1**  **Non -**  **bell pepper 2.0**  **Pi mentos**  **0.1 Sugar beet**  **0.1 Sugar cane**  **0.2 Tomato**  **0.2 ]** 11