EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS

PUBLISHED IN THE FEDERAL REGISTER (11/11/2011)

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 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 (PP # 2F8075) 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 CFR part

180. 5852

1. by amending the tolerances for residues of 

### the herbicide, pyraflufen-ethyl, ethyl 2- chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-1Hpyrazol-3-yl)-4-fluorophenoxyacetate and it s acid metabolite, E-1, 2-chloro-5-(4- chloro-5-difluoromethoxy-1 -methyl-1H-pyrazol-3-yl)-4-f luorophenoxyacetic acid, expressed in terms of the parent, in or on the following commodities: Cattle, meat byproducts; Goat, meat byproducts; Hors e, meat byproducts; Milk; and Sheep, meat byproducts, by extending the expiration date for these temporary tolerances until December 31, 2016.

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 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. **“NA-Remove”**



### 2. Analytical method

. 

### Aqueous organic solvent ex traction, column clean up, and quantitation by gas chromatography with mass spectrometry is used to measure

and evaluate the chemical residues.

3. Magnitude of residues. “NA

‐ Remove”

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 metabolites

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 detected in kidney tissues. These results concur with those of an earlier ruminant3

metabolism study (MRID 45283005) at a dose of 10 ppm. Although the results of this livestock
feeding study indicate that no finite residues are 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 maximum poultry dietar y burden from a diet comprised of cotton meal, corn grain, corn milled byproducts, soybean seed, soybean meal, soybean hulls, wheat grain, and wheat milled byproducts results in a total dietary burden that is significantly lower than th e levels that would require tolerances in poultry and poultry byproducts.

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. [Insert text.] “NA

‐ Remove”4



### EPA has evaluated the available toxici ty data on pyraflufen-ethyl and considered its validity, completeness, and relia bility as well as the relationship of the

results of the studies to human risk. EP A has also considered available information concerning the variability of the sensitivities of major identifiable subgroups of consumers, including infants and children. Specific information on the nature of the adverse effects caused by pyraflufen-e thyl as well as the no-observed-adverseeffect-level (NOAEL) and the lowest-obs erved-adverse-effect-level (LOAEL) from the toxicity studies reviewed can be found at http://www.regulations.gov in the document “Pyraflufen-ethyl: Human Heal th Risk Assessment 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, meta bolized, 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 proposed use.

7. Metabolite toxicology

. 

### No toxicologically significant metabolites

were detected in animal metabolism studies or plant metabolism studies on cotton, potatoes, and mandarin oranges.

8. Endocrine disruption

. 

### Chronic, lifespan, and multigenerational

bioassays in mammals and acute and subchr onic studies on aquatic organisms and wildlife did not reveal any endocrine effect s 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 pyraflufenethyl is negligible.5

C. Aggregate Exposure

1. Dietary exposure. 

### Quantitative acute dietary exposure and 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. No such effects attributable to a single exposure (dose) were observed in oral toxicity studies, including the developmental toxicity studies in rats and rabbits conducted with pyraflufen-ethyl ; therefore, a quantitative acute dietary exposure assessment is not necessary. Chro nic dietary risk analyses were conducted using Dietary Exposure Evaluation Model Software with the Food Commodity Intake Database (DEEM-FCID). These dietary exposure assessments used the following assumptions: 100 percent crop trea ted (PCT) and tolerance-level residues for pyraflufen-ethyl on all treated crop s except corn, cottonseed, potato, soybean, wheat, pome fruit, stone fruit, pomegranat e, olive, grape, tree nuts, pistachio, hops, and peanuts for which one half of the comb ined Levels of Quantification (LOQs) for the parent and the metabolite were used sinc e all field trial residue levels were less than the LOQ. Exposure estimates to wa ter were based on modeling with FIRST, PRZM/EXAMS, and SCI-GROW.

i. Food. 

### Using the exposure assumptions listed above, chronic exposure to pyraflufen-ethyl from food including th e proposed new uses on hops and peanuts will incrementally utilize <1% of the cP AD 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. Ba sed on the First Index Reservoir Screening Tool (FIRST), Pesticide R oot Zone Model/Exposure Analysis Modeling System (PRZM/EXAMS), and Screening Concentr ation in Ground Water (SCI-GROW) models, the estimated drinking water con centrations (EDWCs) of pyraflufen-ethyl for acute exposures are estimated to be 1,247 parts per trillion (ppt) for surface water and 1.8 ppt for ground water. Fo r chronic exposures for non-cancer and cancer assessments, the EDWCs are estimate d to be 281 ppt for surface water and 1.8 ppt for ground water.

2. Non-dietary exposure

. 

### EPA calculated non-dietary exposure scenarios as listed in the Federal Register May 12, 2004 (69 FR 26305) (FRL-7358-6



### 2). Pyraflufen-ethyl is registered in severa l non-food sites, including airports, commercial plants, nurseries and ornament al plantings; established ornamental turf; railroad, roadside, and utility rights-of-ways, and ot her similar non-crop areas.

D. Cumulative Effects



### Pyraflufen-ethyl belongs to the protox inhi bitor class of compounds, and chemically is a 3-phenylpyrazole. The herbicidal acti vity of protox inhibitors is due to the inhibition of protoporphyrinogen IX oxida se. Chemicals with a similar mode of action, i.e., the protox inhibitors, have di fferent chemical structures compared to pyraflufen-ethyl. Although other protox i nhibitors have a simi lar herbicidal mode of action, there is no information available to suggest that these compounds exhibit a similar toxicity profile in the mammalian system. Current available data and information does not indicate or suggest that pyraflufen-ethyl has a common mechanism of toxicity with other substan ces. Therefore, for the purposes of this Food Quality Protection Act (FQPA) document , assessment of cumulative risk is not required.

E. Safety Determination

1. U.S. population.



### i. Acute risk. No adverse effect attri butable to a single exposure (dose) of pyraflufen-ethyl was observed in the oral toxicity studies, including the developmental toxicity studies in rats a nd rabbits. Therefore, an acute reference dose was not established and no acute risk is expected.

ii. Chronic Risk. Based on the chronic to xicity data, the cPAD for pyraflufen-ethyl is considered to be 0.172 mg/kg/day. Th is value is based on the NOAEL of 17.2 mg/kg/day observed in the chronic rat fe eding study and a safety (uncertainty) factor of 100. A worse case estimate, us ing proposed toleran ce values, of chronic dietary exposure of pyraflufen-ethyl from hops and peanuts will utilize less than 1% of the cPAD for the general U.S. populatio n. EPA generally has no concern for exposures below 100% of the RfD because th e RfD represents the level at or below which daily aggregate dietary exposure ov er a lifetime will not pose appreciable7



### risks to human health. The complete toxi city data set and the conservative chronic exposure assumptions support the conclusion that there is a reason able certainty of no harm from dietary (food) exposure to py raflufen-ethyl and the acid metabolite residues. Moreover, as exposure to res idues 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. There is essentially no incremental cancer risk associated with pyraflufen-ethyl treated hops and peanuts. Cancer 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 substantia lly overstates risk because it is based on the assumption that all commodities covered by pyraflufen-ethyl tolerances contain

tolerance level residues. The cancer risk es timate 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 pyraflufenethyl 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 DWLOCs and comparing them to the EDWCs for surface and ground water, it is not exp ected the aggregate exposure to children will exceed the Agency’s level of concern.

There is no evidence of increased susceptibili ty 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 pyraflufen-ethyl. There are no residual un certainties for pre- and/or post-natal

exposure.

F. International Tolerances8



### There are no Codex maximum residue levels (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.