EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER ( 1 /1/2010 ) EPA Registration Division contact: Kathryn Montague Product Manager 23 (703) 305 - 1243

INSTRUCTIONS: Please utilize this outline in preparing the pesticide petition. In cases where the outline element does not apply, please insert “NA-Remove” and maintain the outline. Please do not change the margins, font, or format in your pesticide petition. Simply replace the instructions that appear in green and brackets, i.e., “ [ insert company name ] ,” with the information specific to your action. TEMPLATE: [Nichino America , Inc. ] [Pesticide Petition No. xxxxxx ] EPA has received a pesticide petition (P P # xxxxxx) from Nichino America, Inc. 4550 New Linden Hill Road Suite 501 Wilmington, DE 19808 proposing, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CF R part 180. 585

1. by establishing a tolerance for residues of the herbicide , pyraflufen - ethyl [ ethyl 2 - chloro - 5 - (4 - chloro - 5 - difluoromethoxy- 1 - methyl- 1H pyraz ol-3 -yl) - 4 - fluorophenoxyacetate] and its acid metab olite, E - 1 [ 2 - chloro - 5 - (4 - chloro - 5 - difluo romethoxy- 1 - methyl- 1H -pyrazol-3 -yl) - 4 - fluorophenoxyacetic acid] , expressed in terms of the parent, in or on the following raw agricultural commodities: almond hulls at 0.02 parts per million (ppm) and nuts, tree group 14 at 0.01 parts per million (ppm) , pi stachio at 0. 0 1 parts per million (ppm) , fruit, pome fruit group 11 at 0.01 parts per million (ppm) , fruit, stone fuit group 12 at 0.01 parts per million (ppm) , pomegranates at 0.01 parts per million (ppm) , olives at 0.01 parts per million (ppm) , grapes at 0.01 parts per million (ppm) , and hops at 0.05 parts per million (ppm) . 2. to establish an exemption from the requirement of a tolerance for “NA Remove”2

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 full y 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 qualitative nature of the residues of pyraflufen - ethyl (ET - 751) in corn, soybeans, and wheat and pasture grass is adequately understood. The metabolism of pyraflufen - ethyl has been studied in cotton, wheat, and p otato. Metabolism in the plant involves ester hydrolysis, demethylation on the pyrazole ring and further degradation of the phenoyxyacetate moiety to bound polar metabolites. The nature of the residue is adequately understood and the residues of concern a re the parent, pyraflufen - ethyl, and the acid metabolite, E - 1, only. 2. Analytical method

. Aqueous organic solvent extraction, column clean up, and quantitation by gas chromatography is used to measure and evaluate the chemical residues. 3. Magnitud

e of residues. Several residue trials were conducted in almonds, pecans, apples, pears, grapes, and hops to satisfy the required EPA region location s. Based on these data, it is proposed that the Agency establish new tolerances in almond hulls at 0.02 p pm , nuts, tree group 14 at 0.01 ppm, pistachio at 0.01 ppm , fruit, pome fruit group 11 at 0.01 ppm , fruit, stone fuit group 12 at 0.01 ppm , pomegranates at 0.01 ppm , olives at 0.01 ppm , grapes at 0.01 ppm , and hops at 0.05 ppm. 4 . Magnitude of the residue in animals . --i. Ruminants. The results of the meat and milk 28 - day feeding study conclude that no finite residues of the parent, ET - 751 or the metabolite s E - 9, and E - 15 can be detected in milk at a dose level of 10 ppm, and that no residues of eithe r ET - 751 , E - 5 , or E - 9, are detected in muscle, liver or fat tissues, and low level residues of 0.0534 ppm in kidney tissues. These results concur with those of an earlier ruminant metabolism study (MRID 45283005) at a dose of 10 ppm. Although the results of this livestock feeding study indicates that no finite residues could be detected in meat and milk commodities from the anticipated dietary burdens , we are using an anticipated residue value in milk calculated to be of 0.007 ppm . ii. Poultry. The ma ximum poultry dietary burden results from a diet comprised of cotton meal, corn grain, corn milled byproducts, soybean seed, soybean meal, soybean hulls, wheat grain, and wheat milled byproducts for a total dietary burden that is significantly lower than the levels that would require the proposal of tolerances in poultry. This conclusion is based on the exaggerated rate metabolism studies carried out on pyraflufen - ethyl and its acid metabolite. Therefore, an exemption from tolerances in poultry meat, meat byproducts, fat, and3

eggs under 40 CFR 180.6(a)(3) and (b) is proposed as it is not possible to establish with certainty whether finite residues will be incurred, but there is no reasonable expectation of finite residues.

B. Toxicological Profile 1

. Acute toxicity. [Insert text.] “NA-Remove”

2. Genotoxicty. [Insert text.] “NA -Remove”

3. Reproductive and developmental toxicity. [Insert text.] “NA-Remove”

4. Subchronic toxicity. [Insert text.] “NA -Remove”

5. Chronic toxicity. [Ins ert text.] “NA -Remove” EPA has evaluated the available toxicity data and considered its validity, completeness, and reliability as well as the relationship of the results of the studies to human risk. EPA has also considered available information concern ing the variability of the sensitivities of major identifiable subgroups of consumers, including infants and children. The nature of the toxic effects caused by pyraflufen ethyl as well as the no observed adverse effect level (NOAEL) and the lowest observ ed adverse effect level (LOAEL) from the toxicity studies reviewed are discussed in the Federal Register of April 30, 2003 ( 68 FR 23046) (FRL - 7300 - 9).

6. Animal metabolism. The q ualitative nature of the residues of pyraflufen - ethyl and its acid metabolite, E - 1, in animals is adequately understood. Pyraflufen - ethyl is rapidly absorbed, metabolized, and excreted to feces and urine, with greater than 90% of the administered dose excr eted within 24 hours in rats. Based on metabolism studies with goats, hens, and rats, there is no reasonable expectation that measurable pyraflufen - ethyl- related residues will occur in meat, milk, poultry, or eggs from the proposed use.

7. Metabolite t oxicology . No toxicologically significant metabolites were detected in plant or animal metabolism studies for cotton, potatoes , or mandarine oranges .

8. Endocrine disruption . Chronic, lifespan, and multigenerational bioassays in mammals and acute and subchronic studies on aquatic organisms and wildlife did not reveal any endocrine effects for pyraflufen - ethyl. Any endocrine4

related effects would have been detected in this comprehensive series of required tests. The probability of any such effect due t o agricultural uses of pyraflufen ethyl is negligible.

C. Aggregate Exposure

1. Dietary exposure. Acute dietary risk assessments are performed for a food - use pesticide, if toxicological study has indicated the possibility of an effect of concern o ccurring as a result of a one - day or single exposure. No adverse effect attributable to a single exposure (dose) was observed in oral toxicity studies, including the developmental toxicity studies in rats and rabbits. Therefore, EPA did not identify an a cute dietary endpoint and an acute dietary assessment was n ot performed. Chronic dietary risk analyses was conducted to estimate potential pyraflufen - ethyl residues in/on the following crops: almond, beechnut, Brazil nut, butternut, cashew, chestnut, chi nquapin, filbert, hickory nut, macadamia nut, pecans, walnuts, pistachio, apple, crabapple, loquat, mayhaw, pear, oriental pear, quince, apricot, sweet cherry, tart cherry, nectarine, plum, Chickasaw, Damson plum, Japanese plum, plumcot, fresh prune, pomeg ranates, olives, grapes and hops and anticipated residues in milk of 0.007 ppm, using Dietary Exposure Evaluation Model Software with the Food Commodity Intake Database (DEEM- FCID) . These estimates assuming tolerance level residues in the established and proposed commodities except corn, cottonseed, potato, soybean seeds, and wheat grains had nondetectable residues. Exposure estimates to water were based on modeling with FIRST and SCI - GROW.

i. Food. The chronic population adjusted dose (cPAD) for the general population, based on residues at the tolerance levels and 1⁄2 of the combined LOQs for the parent and metabolites for corn, soybeans, potato, wheat, and cotton . A default processing factor of 6.5 X for dry potato, 1.5x for corn syrup, an experiment al processing factor of 0.6x for cotton seed oil and calculated milk value of 0.007 ppm . One hundred percent crop treated (%CT) was assumed for all crop commodities. The new crops will incrementally utilize <1% of the cPAD of 0.2 mg/kg/day for the U.S. p opulation and <1% of cPAD for children (1 - 6 years) .

ii. Drinking water . The residue of concern in drinking water was determined to be pyraflufen - ethyl. Based on the FIRST and SCI - GROW models, the EECs of pyraflufen - ethyl for acute exposures are estim ated to be 1247 parts per trillion (ppt) for surface water and 1.8 ppt for ground water. The EECs for chronic exposu res are estimated to be 281 ppt for surface water and 1.8 ppt for ground water. 2. Non - dietary exposure . EPA calculated the non - dietary exposure scenarios in the Federal Register May 12, 2004 ( 69 FR 26305) (FRL - 7358 - 2 ). Pyraflufen - ethyl is registered in several non - food sites, including airports, commercial plants, nurseries and ornamental plantings; established ornamental turf; railroad, roadside, and utility rights - of -ways, and other similar non - crop areas.5

D. Cumulative Effects Pyraflufen - ethyl belongs to the protox inhibitor class of compounds, and chemically is a 3 -phenylpyrazole. The herbicidal activity of protox inhibitors is due to the inhibition of protoporphyrinogen IX oxidase. All relevant toxicological data has been provided to EPA. Chemicals with a similar mode of action, i.e., the protox inhibitors, have different chemical structures compared to pyraflufen - ethyl. Alth ough other protox inhibitors have a similar herbicidal mode of action, there is no information available to suggest that these compounds exhibit a similar toxicity profile in the mammalian system. We are aware of no information to indicate or suggest that pyraflufen - ethyl has any toxic effects on mammals that would be cumulative with those of any other chemical. Since pyraflufen - ethyl is relatively non -toxic, cumulative effects of residues and other compounds are not anticipated. Therefore, for the purposes of this Food Quality Protection Act (FQPA) document, there should be no consideration of cumulative risk that would require assessment. E. Safety Determination

1. U.S. population. i. Acute risk. No adverse effect attributable to a single exposure (do se) of pyraflufen - ethyl was observed in the oral toxicity studies, including the developmental toxicity studies in rats and rabbits. Therefore, an acute reference dose was not established and no acute risk is expected. ii. Chronic Risk. Based on the chron ic toxicity data, the cPAD for pyraflufen - ethyl is considered to be 0.172 mg/kg/day. This value is based on the NOAEL of 17.2 mg/kg/day observed in the chronic rat feeding study and a safety (uncertainty) factor of 100, the worse case estimate of chronic d ietary exposure of pyraflufen ethyl from cotton, potatoes, corn, soybean, and wheat, almond, beechnut, Brazil nut, butternut, cashew, chestnut, chinquapin, filbert, hickory nut, macadamia nut, pecans, walnuts, pistachio, apple, crabapple, loquat, mayhaw, p ear, oriental pear, quince, apricot, sweet cherry, tart cherry, nectarine, plum, Chickasaw, Damson plum, Japanese plum, plumcot, fresh prune, pomegranates, olives, grapes and hops and calculated value of 0.007 ppm in milk will utilize less than 1% of the c PAD for the general U.S. population. EPA generally has 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. T he complete and reliable toxicity data and the conservative chronic exposure assumptions support the conclusion that there is a reasonable certainty of no harm from dietary (food) exposure to pyraflufen - ethyl and the acid metabolite residues. Moreover, as exposure to residues of pyraflufen - ethyl and the acid metabolite via water is negligible, there is a reasonable certainty of no harm from aggregate exposure to pyraflufen - ethyl and the acid metabolite residues. iii. Cancer Risk. Cancer risk was calculate d by the EPA in the Federal Register May 12, 2004 (69 FR 26305) (FRL - 7358 - 2) for both food and water. This assessment substantially overstates risk because it is based on the assumption that all6

commodities c overed by p yraflufen - ethyl tolerances contain tolerance level residues. The cancer risk estimate was in the range of 1 in 1 million and does not exceed the Agency’s level of concern for exposure from either food or water sources.

2. Infants and children . The chronic dietary exposure of pyrafluf en ethyl and the acid metabolite from corn, soybeans, and wheat and calculated value in milk will utilize < 1% of the cPAD for children (1 - 6 years). Exposure to potential residues in drinking water is expected to be negligible. In the Federal Register May 12, 2004 (69 FR 26305) (FRL - 7358 - 2) after calculating DWLOCs and comparing them to the EECs for surface and ground water, EPA does not expect the aggregate exposure to children to exceed the Agency’s level of concern. There is no evidence of increased s usceptibility of rat or rabbit fetuses following in utero exposure in the developmental studies with pyraflufen - ethyl. There is no evidence of increased susceptibility of young rats n the reproduction study with Pyraflufen - ethyl. EPA concluded there are no residual uncertainties for pre - and/or post- natal exposure.

F. International Tolerances There are no Codex maximum residue level established for residues of pyraflufen - ethyl and the acid metabolite, E - 1, expressed in terms of parent on any crops.