EPA Registration Division contact: Andrew Ertman ; 703 - 30 8 - 9367 PP #2E8051 EPA has received a pesticide petition ( 2E8051 ) from IR - 4 , IR - 4 Headquarters , Rutgers, The State University of New Jersey , 500 College Road East Suite 201 W , Princeton, NJ 08540 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 residues of fenoxaprop - ethyl , .( [ (±) - ethyl 2 - [ 4 - [ ( 6 - chloro - 2 - benzoxazolyl)oxy]phenoxy]propanoate) and its metabolites 2 - [4 - [ ( 6: - chloro - 2 - benzoxazolyl) oxy] phenoxy] propanoic acid and 6 - chloro - 2,3 - dihydrobenzoxazol - 2 - one, each expressed as the parentcompound in or on the raw agricultural commodities grass, hay at 0. 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; 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. Plant metabolism studies with fenoxaprop - ethyl were performed in wheat, cotton and peanuts . The metabolism in all plants was very similar. The main reactions involved were rapid cleavage of the ethyl ester to form fenoxaprop acid. Next, the benzoxazolyloxy linkage is cleaved, resulting in the formation of AE F054 014 (6 - chloro - 2,3 - dihydro - benzoxazol - 2 - one) . 2. Analytical method. Tolerances are being proposed in grass hay f or the combined residues of fenoxaprop - ethyl and its metabolites fenoxaprop - acid and AE F05414 . The analytical method involves reflux with acid to convert fenoxaprop - ethyl and fenoxaprop acid to AE F05414 , derivatization followed by SPE clean - up. Quantitation is by gas chromatography - mass spectrometry ( GC/MS). 3. Magnitude of residues. Four residue field trials were conducted in Washington and Oregon representing regions 11 and 12. Trials were conducted on bluegrass, fescue (two separate varieties) and ryegrass. No residues greater than the lowest limit of method validation (LLMV, 0.05 ppm) were observed for any of the three analytes in any sa mple. B. Toxicological Profile 1. Acute toxicity. Fenoxaprop - P - ethyl has very low acute toxicity to mammals irrespective of the route of exposure (oral, percutaneous or inhalation exposure). It is non - irritating to eyes and skin, and is not a skin sensitizer ( Buehler ) Overall, it is classified as Toxicity Classification III. The oral LD 50 in rats is greater than greater than 2000 mg/kg. The dermal LD 50 value in rats is greater than 2000 mg/kg. Th e inhalation LC 50 for a four - hour exposure (nose only) is greater than 1.224 m g/ L . Inthe acute oral toxicity study, clinical signs were observed within 1 to 24 hours with recovery within thirteen days after exposure. No clinical signs nor body weight changes or necropsy findings were observed in the dermal toxicity stud y conducted in rats. In the acute inhalation toxicity study, non - specific clinical signs were observed with recovery within five days after exposure. Fenoxaprop - p - ethyl is a member of th e arloxy phenoxy - propionate class of herbicides , b ased on structural similarity of the arloxy phenoxy - propionate herbicides, knowledge of the mode of action for these compounds, and lack of neurotoxicity for this class, the acute neurotoxicity study is not required for fenoxaprop - P - ethyl. 2. Genotoxicty

. Genotoxicity potential was evaluated in a series of tests including in vitro and in vivo tests. There was no indication of gene mutation either in the presence or absence of metabolic activation in both the bacterial reverse mutation and mammalian gene mutation tests. The in vitro chromosome aberration test and the in vivo mouse micronucleus test were also both negative. These studies demonstrate that fenoxaprop - P - ethyl has no genotoxic potential. 3. Imm unotoxicity

. Immunotoxicity potential was evaluated in a four week study in female rats. Following immunization with SRBC antigen, mean anti - SRBC IgM concentrations were similar to the untreated control group at all dose levels tested. The high dose of 630 ppm ( 47 mg /kg bw/day ) was determined to be the NOEL for immunotoxicity for females. Fenoxaprop - P - ethyl is therefore, n ot considered to be immunotoxic. 4. Reproductive and developmental toxicity. In a rat two - generation fenoxaprop - ethyl reproduction s tudy, the parental systemic NOAEL was 5 ppm ( 0.25 mg/kg/day ) based on decreased in total lipids in F 1 males and females and total cholesterol in F 1 males . The reproductive LOAEL of 1.5 mg/kg/day was based on reduced pup body weights (F 1a ). The US EPA determined that the fenoxaprop ethyl reproduction study and chronic toxicity studies may be used to bridge with fenoxaprop - p - ethyl. In a rat developmental toxicity study, the NOAEL was 32 mg/kg/day both in the dam (based on a reduction in body w eight gain, food consumption and heart weight) and in terms of fetal development (based on delayed ossification of the cranial bones and the absence of any other findings) . No evidence of a teratogenic effect was observed at any dose level tested. In a ra bbit developmental toxicity study, the NOAEL was 32 mg/kg/day both in the dam ( based on decreased food consumption, stagnation of body weight gains during the treatment period, and increased kidney weights ) and in terms of fetal development ( visceral and skeletal effects observed at the high dose ) . No evidence of a teratogenic effect was observed at any dose level tested. 5. Subchronic toxicity. Subchronic studies showed that the liver is the major target organ in rats and mice . In addition to the liver, the kidney ( females ) was also a target organ in mice . In the female mouse , moderate to marked renal tubularinjury was observed at the high dose . In dogs , a decrease in bodyweight gain and an increase in ASAT and total protein for the males as well as a decrease in ALAT for both sexes were observed at the highest dose tested (2000 ppm, ca. 81 mg/kg bw) . The rat was the most sensitive species followed by the mouse with the dog being the least sensitive. Overall, the lowest NOAEL was observed in the subchronic rat study. In this study, the NOAEL for the rat was established at 0.75 mg/kg bw/day. Fenoxaprop - p - ethyl is a member of the arloxy phenoxy - propionate cla ss of herbicides, based on structural similarity of the arloxy phenoxy - propionate herbicides, knowledge of the mode of action for these compounds, and lack of neurotoxicity for this class, the subchronic neurotoxicity study is not required for fenoxaprop - P - ethyl. 6. Chronic toxicity. The US EPA determined that the fenoxaprop - ethyl chronic toxicity studies may be used to bridge with fenoxaprop - p - ethyl. In a two year dog study No treatment related effects 'were seen on mortality, behavior, clinical findings, food consumption, hematology , kidney and liver function, or urinalysis. Neurologic, ophthalmologic, otologic, dental, and mucosal health were similar in the treated and control animals. In addition, dosing did not cause toxicologically important effects on organ weights, organ - to - bod y weight ratios, or gross and histopathological findingsThe NOEL was 15 ppm (0.375 mg/kg/day) and the LOEL, based on decreases in body weight gain, was 75 ppm (1.875 mg/kg/day). In the rat, at the end of the combined chronic toxicity and carcinogenicity study treatment did not affect mortality, behavior, clinical findings, body weight, food consumption, hematology, kidney and liver function, or urinalysis. In addition, dosing did not causetoxicologically important effects on organ weights, organ - to body weight ratios, or gross and histopathological findings. For chronic toxicity, the NOEL was 30 ppm {1.5 mg/kg/day) and the LOEL was 180 ppm (9 mg/kg/day) based on decreased serum li pids and cholesterol in the males. Under the conditions of this study, there was no evidence of carcinogenic potential. In a mouse carcinogenicity study the target organ was the liver. Treatment had no effect on mortality. Clinical observations indicated a n increased incidence of swollen abdomen in both sexes at the mid and high dose from week 55 onward. In males only, absolute liver weight and relative liver weight was increased. Histopathology revealed alterations in the liver characterized as hepatocellu lar hypertrophy, single cell necrosis, pigmentation in macrophages and lipofuscin deposit at mid dose (males) and high (males and females) . For chronic toxicity, the NOEL was 40 ppm (5.7 mg/kg/day), and the LOEL was 115 ppm (16.6 mg/kg/day) based on hist opathological findings in the liver. There was evidence of carcinogenicity at the highest dose tested. Statistically (p <0. 05) significant increases were seen in liver and adrenal gland tumors. 7. Animal metabolism. In the rat, fenoxaprop - P - ethyl is rap idly absorbed and excreted. Based on a comparison of the radioactivity excreted after oral and intravenous treatment, the oral absorption rates can be estimated at about 84% for the male rats and roughly 96% for the female rats indicating an almost complet e oral absorption. Fenoxaprop - P - ethyl was extensively metabolized with unchangedparent compound found only in low percentages of the recovered dose. The metabolism of fenoxaprop - P - ethyl in male and female rats was similar and included hydrolysis of the et hyl ester, followed by cleavage to afford the (D+) - 2 - (4 - (hydroxyphenoxy) - propionic and 6 - chloro - 2,3 - dihydro - (benzoxazol - 2 - one) , hydroxylation , conjugation and sulphatation . In ruminants and poultry, fenoxaprop - ethyl is rapidly excreted and the principal route of metabolism is similar to that described for the rat above . Fenoxaprop - ethyl residues do not accumulate in animal tissues, milk or egg s. 8. Metabolite toxicology

. Not applicable as parent is the compound of concern. 9. Endocrine disruption

. Ther e is no evidence to suggest that fenoxaprop - P ethyl has any primary endocrine disruptive potential. Reproductive and developmental findings provided no evidence of an enhanced sensitivity of the young. Bayer CropScience will conduct any studies that may be required under EPA’s Endocrine Disrupter Screening Program. C. Aggregate Exposure 1. Dietary exposure

. The toxicological and exposure database for fenoxaprop P - ethyl is considered complete. There was no indication of an increased sensitivity of the young in any studies including the reproductive and developmental studies in rats and rabbits. Therefore, the special FQPA can be reduced to 1X and an uncertainty factor of 100 is adequate to account for inter - and intra - species variability. Acute and c hronic Population Adjusted Doses (aPAD and cPAD) are, therefore, the same as the reference doses for the populations and subpopulations of interest. Acute dietary exposure was expressed as a percentage of the aPAD of 0. 32 mg/kg bw/day based on a NOAEL of 32 mg/kg bw/day in the rat developmental toxicity study with an uncertainty factor of 100. Chronic dietary exposure was expressed as a percentage of the chronic Population Adjusted Dose (cPAD) of 0. 0025 mg/kg bw/day based on a NOAEL of 0.25 mg/kg bw/day i n the rat reproductive study with an uncertainty factor of 100. i. Food. Since no fenoxaprop - P - ethyl residues were detected on grasses grown for seed, there would be minimal change to the previous FQPA human health risk for fenoxaprop - P - ethyl in February 1998 (DP Barcode D242374, S. Kizner, 2/3/98). Bayer CropScience is not conducting a revised risk assessment for this new use for the following reasons: 1.) this label expansion does not involve use on human foods; 2.) it is unlikely to alter the dietary burden for livestock. There would be negligible changes to the results of the 1998 assessment as summarized below. A Tier 1 acute and chronic dietary risk assessments were conducted to evaluate the dietary exposure of the U.S. population and selected subpopulations to fenoxaprop residues. The assessment assumed residues would be at tolerance levels for fenoxaprop and 100% of the crops were treated. The Tier I acute and chronic assessments were conducted using DEEM - FCIDTM, Version 2.14 so ftware. Consumption data used in this program were taken from USDA’s CSFII, 1994 -1996, 1998. With these conservative assumptions, acute exposure for food only utilizes 0.3% of the aPAD for the Females 13 - 49. Chronic exposure for food and water only util izes 0.4% of the cPAD for the US Population. ii. Drinking water. The use of PUMA herbicide on grasses grown for seed would have a negligible impact on the estimates of drinking water residues for fenoxaprop - P - ethyl . In the human health assessment (2/3/98) , EFED used the “GENEEC” drinking water model to generate Tier I estimated exposure concentrations (EEC) of surface water runoff. The GENEEC screening model calculated peak EECs for fenoxaprop - ethyl of 27 ppt and 56 - day EEC's of 0.56 ppt. For fenoxaprop - acid, the peak EEC was 410 ppt and the 56 - day EEC was 87 ppt. These drinking water values did not significantly increase dietary exposure. In conclusion, the results of the very conservative acute and chronic dietary exposure analyses (including food and drinking water) demonstrates that fenoxaprop exposure consumes a very small percentage of the risk cup for all scenarios and population subgroups examined. Therefore, there is a reasonable certainty that no harm will result from exposure to potential resi dues of fenoxaprop in food and water. 2. Non

- dietary exposure

. The maximum seasonal and single use rate has not changed and no new methods of application or field post application activities are introduced by the additional crops. Hence, a risk to bystanders, field workers, and applicators is not expected to change from the current acceptable levels. D. Cumulative Effects Section 408(b)(2)(D)(v) requires that, when considering whether to establish, modify, or revoke a tolerance, the Agency conside r “available information” concerning the cumulative effects of a particular pesticide’s residues and “other substances that have a common mechanism of toxicity.” EPA has not made a common mechanism of toxicity finding as to fenoxaprop - P - ethyl and any othe r substances and fenoxaprop - P - ethyl does not appear to produce a toxic metabolite produced by other substances. E. Safety Determination 1. U.S. population. Risk assessments for fenoxaprop - P - ethyl are based on a complete and reliable toxicity data package and highly conservative assumptions. Chronic aggregate dietary exposure (food and water) utilizes <1 % of the cPAD for the US Population. Acute aggregate dietary exposure (food and water) for the U.S. adult population utilizes <1 % of the aPAD. Non - occupa tional non - dietary exposure of the U.S. population to fenaxoprop - p - ethyl is not expected to change. Therefore, there is a reasonable certainty that no harm will occur to the US Population from aggregate exposure (food and drinking water) to residues of fe noxapro p - P - ethyl . 2. Infants and children

. The toxicological and exposure database for fenoxaprop - P - ethyl is considered complete. There was no indication of an increasedsensitivity of the young in any studies including the reproductive and developmental studies in rats and rabbits. Therefore, the special FQPA can be reduced to 1X and an uncertainty factor of 100 is adequate. Based on conservative assumptions, chronic aggregate dietary exposure (food and water) utilizes <1 % of the cPAD for Females 13 to 4 9 yrs. old , the most highly exposed subpopulation. Acute aggregate dietary exposure (food and water) utilizes <1 % of the aPAD for all subpopulations . Non - dietary exposure of children to fenoxaprop - P - ethyl is not anticipated. Therefore, there is a reason able certainty that no harm will occur to infants andchildren from aggregate exposure (food and drinking water) to residues of fenoxaprop - P - ethyl . F. International Tolerances No tolerances have been established for fenoxaprop - P - ethyl .