EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE

PETITIONS PUBLISHED IN THE FEDERAL REGISTER EPA Registration Division contact: Kathryn Montague 703
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- 1243 Bayer CropScience LLC PP# 9F 7679 EPA has received a pesticide petition ( 9F7679) from Bay er CropScience LLC, 2 T. W. Alexander Drive, Research Triangle Park, NC 27709 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 res idues of the herbicide safener, mefenp yr - diethyl including its metabolites and degradates. Compliance with the tolerance levels specified is to be determined by measuring residues of mefenpy r - diethyl ((

RS )

- 1

- (2,4

- dichlorophenyl)

- 5

- methy l

- 2

- py razoline

3,5

- d icarbox yl ic acid) and its dichloropheny lpy razoline metabolites] in or on the raw agricultural commodity

[sorghum, grain] at [0.01] parts per million (ppm); [sorghum, forage] at [0.1] ppm; [sorghum, stover] at [0.05] ppm; [grass, hay] at [0.05] ppm; and [gr ass, forage] at [1.5] ppm. 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. The nature of mefenp yr - diethyl residues in plants and livestock is adequatel y understood. The residues of concern are combined residues of mefenpy r - diethyl, also known as 1

- (2,4

- dichloropheny l)

- 4,5

- dihy dro

- 5

- methy l

- 1H

- py razole

- 3,5

- dicarbox yl ic acid, diethy l ester and its 2,4

- dichlorophenyl

- py razoline metabolites. 2. Analytical method. An enforcement method fo r plants has been developed and radiovalidation and independent laboratory validation (ILV) conducted. The EPA has concluded that this method is suitable for food tolerance enforcement of mefenp yr - diethyl and its 2,4

- dichlorophen yl

- py

razoline metabolites. M

- 36Ü357

- Ü1

- 1 3. Magnitude of residues. The appropriate number of residue trials was conducted in sorghum and grasses in the appropriate locations in the United States to support the requested tolerances on the sorghum and grass commodities. Specificall y, twelve field trials were conducted to measure the magnitude of total mefenpy r - diethyl residues in/on sorghum forage, grain, and stover or grass hay and forage following two foliar spray applications of HUSKI E herbicide to sorghum or grass. Residues of mef enpy r - diethyl and 2,4

- dichloropheny l

- py razoline metabolites were quantified in the harvested matrices (sorghum grain, forage and fodder as well as grass hay

and grass forage) following a postemergence application of Huskie Herbicide. The highest average fi eld trial (HAFT) total mefenpy r - diethyl residue in sorghum forage harvested at a 0

- day

PHIwas 1.1 ppm (maximum residue 1.2 ppm); There were no total mefenp yr - diethy l residues greater than the LOQ (0.10 ppm) in sorghum forage harvested at either a target 7

- day

PHIor at ECH. There were no total mefenpy r - diethyl residues greater than the L OQ (0.01 ppm) in sorghum grain. The HAFT total mefenpy r - diethyl residue in sorghum stover was 0.06 ppm (maximum residue 0.06 ppm). The total mefenp yr - diethyl residue decrea sed with time in sorghum earl y forage but could not be assessed in ECH forage, grain, or stover due to residues being below the LOQ. The HAFT total mefenp yr - diethyl residue in grass forage harvested at a 0

- day PHIwas 1.4 ppm(maximum residue 1.4 ppm). The HAFT total mefenpy r - diethyl residue in grass forage harvested at a 7

- day PHI was 1.2 ppm (maximum residue 1.2 ppm). No residues greater than the LOQ of 0.05 ppm were observed in any of the hay

samples harvested at a target 30

- day PHI

. B. Toxicological Pro

file The Agency

published complete reviews of the safety of mefenpy

r - diethyl in the ‘Final Rule’ published in the Federal Register April 30, 2003 (Volume 68, Number 83, Pages 23038

- 23046), and in the Federal Register December 10, 2008 (Volume 73, No. 238, pages 74972

- 74979). 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 concerning the variability of the sensitivities of major identifiable subgroups of consumers, including infants and children. 1. Acute toxicity. Mefenpy r - diethyl has low acute toxicity by the oral, dermal, and inhalation routes of exposure. It is not a dermal irritan t but is a slight dermal sensitizer and ocular irritant. 2. Genotoxicty. Mefenpyr

- diethyl did not show any genotoxic potential. 3. Reproductive and developmental toxicity. Developmental toxicity was not observed in the rat at the limit dose (1,000 milligrams/kilogram/day (mg/kg/day)) but was observed in the rabbit (abortions) at the same dose level producing maternal toxicity . Mefenpy r - diethyl did not induce an y signs of reproductive toxicity or neurotoxic potential. The developmental toxicity studies in rats and rabbits, as well as the reproductive toxicity study in rats, did not demonstrate any prenatal or postnatal sensitivity . There was no evidence of reproductive toxicity following exposure via the diet at concentrations of 0, 200, 1000, and 5000 ppm fo r two generations. There is a lack of evidence of neurotoxicity in an y stud y on mefenp yr - diethyl and therefore there is no concern for neurotoxicity resulting from exposure to mefenp yr - diethyl. 4. Chronic toxicity. Repeat exposure via the dermal route did not induce any treatmentrelated effects at dose levels up to and including the limit dose. Repeated exposure studies via the oral route demonstrated that the target organs are the liver and hematopoietic sy stem in dogs, mice, and rats. Mefenp yr - diethy l was negative for carcinogenicity in rats and mice, and classified as ``not likely

to be carcinogenic to humans.'' 5. Animal metabolism. Metabolism studies indicate that mefenp yr - diethyl is rapidly metabolized, widely

distributed, and primaril y excreted via th e urine and feces during the first 24 hours. 7. Metabolite toxicology . The metabolic profile for mefenpy r - diethyl appears to be substantially

similar in plants, animals and the environment. The primary identified metabolites in rats, ruminants, poultry, pl ants and the environment are the three 2, 4

- dichlorophen yl py

razolone metabolites which are included in the risk assessment and for tolerance setting purposes. C. Aggregate Exposure 1. Dietary exposure. Assessments were conducted to evaluate potential risks due to chronic and acute dietary exposure of the U.S. population and selected population subgroups to residues of mefenp yr - diethy l and its two 2,4

- dichloropheny l

- py razoline metabolites. These assessments included current and proposed uses of mefenp yr - diethy l. Exponent Inc.'s Dietary

Exposure Evaluation Model (DEEM

- FCID , Version 2.14), which is licensed to Bay er, was used to estimate the chronic and acute dietary exposure. This software uses the food consumption data from the 1994

- 1998 USDA Continuing Survey s of Food Intakeby

I ndividuals (CSFII 1994

- 1998). No appropriate endpoint attributable to a single exposure (dose) was identified from oral toxicity studies in the database. Therefore, an acute dietary endpoint was not selected and an acute dietary

risk assessment was not conducted. The cRfD was established based on increased liver weights in the chronic dog stud y. The LOAEL for this stud y was 260 mg/kg/day (M/F) with a NOAEL = 51.0 mg/kg/day. This study is supported b y the chronic rat study, which shows a similar NOAEL (48 mg/kg/day). Application of the normal 100X uncertainty factor results in a cRfD/cPAD of 0.51 mg/kg/day

. Results from the chronic dietary exposure anal ys is described below demonstrate a reasonable certaint y of no harm to the overall U.S. population or an y population subgroup from the proposed use of mefenpy r - diethyl on sorghum and grass grown for seed. i. Food. The tier 1 chronic risk assessment was conducted using the results of field trials conducted at maximum label application rates and the shortest pre

- harvest intervals on the proposed label. No adjustments were made to account for dissipation of residues during storage, transportation from the field to the consumer, washing or peeling. Therefore, the actual dietary exposure will be less than that presented here. The chronic dietary

exposure esti mated the percent of the chronic reference dose (cRfD) for the overall US population and various subpopulations. In this anal ys is, total exposure was less then 1% of the chronic RfD for the US Population and all population subgroups. Therefore, the chronic exposure estimates are below EPA's level of concern for the overall U.S. population as well as all subpopulations. ii. Drinking water . EPA’s Tier 1 EDWCs for surface and ground water were generated using FI RST and SCIGROW, respectivel y. Based on the resul ts of these simulations, EPA recommended a chronic EDWC of 3 μg/Lfor use in the human

- health risk assessment. Potential water residues are included in the dietary exposure calculated above. D. Cumulative Effects EPA has not made a common mechanism of toxicity finding for mefenp yrdiethyl and an y other substances and mefenp yr - diethyl does not appear to produce a toxic metabolite produced b y other substances. Therefore, EPA has not assumed that mefenp yr - diethy l has a common mechanism of toxicity with other substances. E. Safety Determination 1. U.S. population . Using the conservative exposure assumptions described above and based on the completeness of the toxicity data, it can be concluded that aggregate exposure to residues of mefenp yr - diethyl presents a reasonable certainty of no harm. No appropriate endpoint attrib utable to a single exposure (dose) was identified from oral toxicity

studies in the database. Therefore, an acute dietary endpoint was not selected and an acute dietary risk assessment was not conducted. The chronic assessment indicated that exposure from residues in crops utilized <1% of the chronic RfD for the U. S. Population when food and water are included. EPA generall y has no concerns for exposures below 100% of the cRfD. An aggregate assessment for the proposed uses for mefenp yr - diethyl demonstrates that there is a reasonable certainty

that no harm will result to the US Population from these uses of mefenp yr - diethy l. 2 . Infants and children . FFDCA section 408 provides that EPA shall apply anadditional tenfold margin of safet y for infants and childre n in the case of threshold effects

to account for pre and post natal toxicity and the completeness of the data base unless EPA determines that a different margin of safet y will be safe for infants and children. The toxicological database for mefenp yr - diethyl is complete for FQPA purposes and there are no residual uncertainties for pre

- /post

- natal toxicity for mefenpy

r - diethyl. Based on the available toxicity

data the Special FQPA Safet y Factor can be reduced to 1x. B ased on the exposure assessments described above and on the completeness and reliability of the toxicity

data, it can be concluded that the dietary exposure from the proposed uses for mefenpy r - diethyl consumes <1% of the cRfD for all subpopulations. Thus, it can be concluded that there is a reasonable certainty that no harm will result from aggregate exposure to mefenp yr - diethyl residues. F. International Tolerances No Codex, Canadian, or Mexican maximum residue limits (MRL s) are established for residues of mefenp yr - diethyl and metabolites in crop or livestock commodities.