**EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR**

**PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER (**  **1 1/11/2011**  **) 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 for ma**  **t 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 4 0 CFR 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 -**  **dif**

**luoromethoxy -**  **1 -**  **methyl -**  **1H -** **pyrazol -** **3 -** **yl) -**  **4 -**  **fluorophenoxyacetic acid ,**  **expressed in terms of the parent, in or on the following raw agricultural commodities:**  **hop, dried cone at 0.01 parts per million (ppm), peanut at 0.01**  **parts per million (ppm)**  **, peanut, hay**  **a t 0.**  **0 7**  **parts per million (ppm) , peanut, meal**  **at 0.01 parts per million (ppm)**  **, and peanut, refined oil at 0.01**  **parts per million (ppm) .**  2. to establish an exemption from the requirement of a tolerance for **“NA**   ** Remove”** 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 the2

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**  **- 75**  **1) in hops, peanuts, peanut hay, peanut meal, and peanut refined oil**  **are adequately under**  **stood. The metabolism of pyraflufen**  **- ethyl has bee**  **n studied in cotton, wheat,**  **potato , and oranges**  **. Metabolism in the plant involves**  **ester hydrolysis, de -**  **methylation 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 are the parent, pyraflufen -**  **ethyl, and the acid metabolite, E**  **- 1, only.**  2. Analytical method

. **Aqueous organic solvent extraction, column clean up, and quantitatio**  **n by gas chromatography with mass spectrometry**  **is used to measure and evaluate the chemical residues.**  3. Magnitude of residues. **R esidue trials were conducted in**  **hops and peanuts to satisfy the**  **required EPA region location s.**  **Other than peanut hay, ther e were no**  **residues found in any hop, peanut, or peanut processed samples above the limit of quantitation for the analytical method established at 0.005 ppm.**  **Based on these data, it is proposed that the Agency**  **establish new tolerances in hop, dried cone at**  **0.01 ppm**  **, peanut**  **at 0.01 ppm, peanut hay at 0.07**  **ppm , peanut meal**  **at 0.01 ppm**  **, and peanut refined oil**  **at 0.01 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**  **no residues of either ET -**  **751 ,**  **E -**  **5 ,**  **or E -**  **9, are detected in muscle, liver or fat**  **tissues, and low level residues of 0.0534**  **ppm were detect ed 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 l ivestock feeding study**  **indicate that no finite residues are**  **detected in meat and milk commodi ties from the**  **anticipated dietary burdens , we are using**  **an anticipated residue value in milk**  **calculated to be of 0.007 ppm .**  **ii. Poultry. The maximum poultry dietary burden**  **from a diet comprised of cotton meal, corn grain, corn milled byproducts, soybe**  **an seed, soybean meal, soybean hulls, wheat grain,**  **and wheat milled byproducts results in a total dietary**  **burden that is significantly lower than the levels tha t would require**  **tolerances in poultry**  **and poultry byproducts.**

B. Toxicological Profile3 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. **[Inse rt text.]**  **“NA -** **Remove” EPA has evaluated the available toxicity data**  **on pyraflufen -**  **ethyl 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**  **concerning the variability of the sensitivities of major ident ifiable subgroups of**  **consumers, including infants and children.**  **Specific information on the nature of the adverse**  **effects caused by pyr aflufen**  **- ethyl as well as the no**  **- observed**  **- adve**  **rse**   ** effect****- level (NOAEL) and the lowest** **- observed**  **- a**  **dverse -**  **effect -**  **level (LOAEL) from the toxicit** **y studies reviewed can be found at**  **http://www.regulations.gov in the**  **document “Pyraflufen -**  **ethyl: Human Health Risk Asse ssment for a Section 3**  **Registration of New Food Uses on Tree Nuts (Crop Group 14), Pistachios, Pome Fruit (Crop Group 11**  **- 10), and Stone Fruit (Crop Group 12), Hops, Grapes, Olives,**  **and Pomegranates,” at page 17 in docket ID number EPA -**  **HQ -**  **OPP -**  **2010 -**  **0426.**

6. Animal metabolism. **The qualitative 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 excreted 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 prop**  **osed use.**

7. Metabolite toxicology . **No toxicologically significant metabo lites**  **were detected in animal**  **metabolism studies or plant metabolism studies on**  **cotton, potatoes**  **, and mandarin**  **oranges .** 

8. Endocrine disruption . **Chronic, lifespan, and multig enerational**  **bioassays in mammals and acute and subchronic studies on aquatic organisms and wildlife did not reveal any endocrine effects for pyraflufen**  **- ethyl.**  **Any endocrine related effects would have been detected in this comprehensive series of required**  **tests. The probability of any such effect due to agricultural uses of pyraflufen**  **** **ethyl is negligible.**4

C. Aggregate Exposure

1. Dietary exposure. **Quantitative a cute dietary**  **exposure and risk**  **assessments are per formed for a food**  **- use pesticide**  **if a**  **toxicological study has indicated the possibility of an effect of concer** **n occurring as a result of a 1 -**  **day or**  **single exposure. No such effect**  **s attributable**  **to a single exposure (dose) were observed in oral toxicity studies, including the developmental to**  **xicit y studies in rats**  **and rabbits conducted with pyraflufen**  **- ethyl**  **; therefore, a quantitative acute**  **dietary exposure assessment is not**  **necessary. Chronic dietary**  **risk analyses were conducted**  **using Dietary Exposure Evaluation Model Software with the Food C ommodity**  **Intake Database (DEEM -**  **FCID) .**  **These dietary exposure assessments used the following assumptions: 100 percent crop treated (PCT) and tolerance** **- level residues**  **for pyraflufen -**  **ethyl on all treated crops except corn, cottonseed, potato, soybean, wheat** **, pome fruit, stone fruit, pomegranate, olive, grape, tree nuts, pistachio, hops, and peanuts for which one half of the combined Levels of Quantification (LOQs) for**  **the parent and the metabolite were used since all field trial residue levels were less**  **than the LOQ.**  **Exposure estimates to water were based on modeling with FIRST**  **, PRZM/EXAMS,**  **and SCI -**  **GROW.**

i. Food. **Using the exposure assumptions listed above, chronic exposure to pyraf**  **lufen -**  **ethyl from food including the proposed new uses on hops and peanuts**  **will incrementally**  **utilize <1% of t he cPAD**  **of 0.172**  **mg/kg/day for all population**  **groups.** ii. Drinking water . **The residue of concern in drinking water was determined to be pyraflufen**  **- ethyl.**  **Based on the Fi**  **rst Index Reservoir Screening Tool (** **FIRST ), Pe**  **sticide Root Zone Model/Exposure Analysis Modeling System (PRZM/EXAMS),**  **and Screening Concentration in Ground Water**  **( SCI**  **- GROW** **) models, the**  **estimated drinking water concentrations (EDWCs) of pyraflufen**  **- ethyl**  **for acute exposures are estimated to be 1**  **, 247 par** **ts per trillion (ppt) for surface water and 1.8 ppt**  **for ground water. F**  **or chronic exposu res**  **for non -**  **cancer and cancer assessments, the EDWCs**  **are estimated to be 281 ppt for surface water and**  **1.8 ppt for ground water.** 

2. Non - dietary exposure . **EPA calcula ted**  **non -**  **dietary exposure scenarios**  **as listed in the**  **Federal Register May 12, 2004**  **( 69 FR**  **26305) (FRL -**  **7358 -**  **2 ).**  **P yraflufen**  **- ethyl**  **is registered**  **in several non -**  **food sites, including airports,**  **commercial plants, nurseries and ornamental plantings; established o rnamental**  **turf; railroad, roadside, and utility rights**  **- of**  **- ways, and**  **other similar non -**  **crop areas.** D. Cumulative Effects **Pyraflufen -**  **ethyl belongs to the protox inhibitor class of compounds, and chemically is a 3**  **- phenylpyrazole.**  **The herbicidal act ivity of protox inhibitors is due to the** 5

**inhibition of pr otoporphyrinogen IX oxidase.**  **Chemicals with a similar mode of action, i.e., the protox inhibitors, have different chemical**  **structures compared to pyraflufen**  **- ethyl.**  **Although 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 mammal** **ian system. Current available data and**  **information does not indicate or suggest that pyraflufen**  **- eth** **yl has a common**  **mechanism of toxicity with other substances. Therefore, for the purposes of this**  **Food Quality Protection Act ( FQ**  **PA) document, assessment of cumulative risk is not required.**  E. Safety Determination

1. U.S. population. **i. Acute risk. No**  **adverse effect attributable to a single exposure (dose) 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 r isk is expected.**  **ii. Chronic Risk. Based on the chronic toxicit** **y 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 ( uncertain**  **ty) factor of 100. A**  **worse case estimate , using proposed tolerance values,**  **of chronic dietary exposure o**  **f pyraflufen -**  **ethyl from hops**  **and peanuts w** **ill utilize less than 1%**  **of the cPAD for the general U.S.**  **population. EPA generally has no concern for**  **expos ures 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.**  **The complete toxicity data**  **set and the conservative chronic**  **exposure assump tions 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 negl** **igible, there is a reasonable certainty of no harm from aggregate exposure to pyraflufen**  **- ethyl and the acid metabolite residues.**  **iii. Cancer Risk. There is essentially no incremental cancer risk associated with**  **pyraflufen -**  **ethyl treated hops and peanuts. Ca**  **ncer risk was calculated by EPA**  **as listed**  **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 all commodities c overed by p**  **yraf lufen**  **- 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 chro**  **nic dietary exposure of pyraflufen**   ** ethyl and** **the acid metabolite from hops and peanuts**  **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 DWL OCs and comparing them to the EDW**  **Cs for**6

**su rface and ground water, i** **t is not expected the aggregate exposure to**  **children will exceed**  **the Agency’s level of concern. There is no evidence of increased susc**  **eptibility 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 in the reproduction study with**  **p y**  **raflufen -**  **ethyl. T here are no residual unce**  **rtainties for pre -**  **and/or post -**  **natal exposure.**  F. International Tolerances **There are no Codex maximum residue level s (MRLs)**  **established for residues of pyraflufen**  **- ethyl and the acid metabolite, E**  **- 1, expressed**  **in terms of parent on any crop**  **. Canada**  **has not established MRLs for pyraflufen**  **- ethyl.**