EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING

FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER (4/9/2010) EPA Registration Division contact: [Bethany Benbow (703) 347 - 8072] INSTRUCTIONS: Please utilize thi s 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 instructi ons that appear in green and brackets, i.e., “ [insert company name] ,” with the information specific to your action. TEMPLATE: [Syngenta Crop Protection, Inc.] [0F7719] EPA has received a pesticide petition ([0F7719]) from [Syngenta Crop Protection, Inc.], [ P.O. Box 18300, Greensboro, NC 27419] 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. (Options (pick one) 1. by establishing a tolerance for residues of [Trinexapac - ethyl: 4 - (cyclopropyl - α - hydroxy - methylene) - 3,5 - dioxo cyclohexanecarboxylic acid ethyl ester expressed as its primary metabolite CGA 179500: 4 - (cyclopropyl - α - hydroxy - methylene) - 3,5 - dioxo - cyclohexanec arboxylic acid] in or on the raw agricultural commodity [] at [] Grass, forage, grown for seed at 1.60 parts per million (ppm) Grass, hay, grown for seed at 3.5 parts per million (ppm) Grass, seed screenings, grown for seed at 45.0 parts per million (ppm) Grass, straw, grown for seed at 12 parts per million (ppm) Cattle, fat at 0.05 parts per million (ppm) Cattle, meat at 0.05 parts per million (ppm) Cattle, meat byproducts at 0.05 par ts per million (ppm) Goat, fat at 0.05 parts per million (ppm) Goat, meat at 0.05 parts per million (ppm) Goat, meat byproducts at 0.05 parts per million (ppm)2 Horse, fat at 0.05 parts per million (ppm) Horse, meat at 0.05 parts per million (ppm) Horse, meat byproducts at 0.05 parts per million (ppm) Sheep, fat at 0.05 parts per million (ppm) Sheep, meat at 0.05 parts per million (ppm) Sheep, meat byproducts at 0.05 parts per million (ppm) EPA has determ ined 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 petiti on. Additional data may be needed before EPA rules on the petition. A. Residue Chemistry 1. Plant metabolism. The metabolism of trinexapac - ethyl is adequately understood for the purpose of the proposed tolerances. The metabolism of trinexapac ethyl has been characterized in grasses grown for seed, spring wheat, and greenhouse grown padd y rice. The primary metabolic pathway was very similar in these three separate crops. 2. Analytical method. Sy

ngenta Crop Protection is submitting Analy tical Method GRM020.01A for the Determination of Residues of Trinexapac - eth ylas CGA - 179500 in Crops by L C - MS/MS for detecting and measuring levels of trinexapac - eth yl expressed as its major metabolite CGA - 179500, in or on food with a limit of quantitation (LOQ) that a llows monitoring of food with residues at or above the levels set in the proposed tolerances. Method validation data using this method on various crop commodities is presented in the validation study . The limit of quantitation (L OQ) for CGA - 179500 is 0.01 ppm for all matrices. Sy ngenta Crop Protection is also submitting Analy tical Method REM 137.14 for the Determination of Residues of Trinexapac Acid (CGA 179500) in Animal Matrices. The limit of quantification has been set at 0.01 mg/ kg with final analy s is by L C MS/MS for egg, kidney , liver, muscle and fat. The limit of quantification has been set at 0.005 mg/ kg for LC - MS/MS determination for milk. ii. Livestock. Because residues in the animal diets indicate that the transfer of residues will be at or n ear the limit of detection, Sy ngenta Crop Protection, Inc. proposes that the Nature of Residue study can be used to define the Magnitude of Residue in livestock. 3. Magnitude of residues. Complete residue data to support the requested tolerances for grass es grown for seed have been submitted. The requested tolerances are adequatel y supported. i. Grasses Grown for Seed. According to Table 5 of OPPTS 860.1500, grass trials are to be conducted in “All Areas Across the Country”. Representative crops for Crop Group 17: Grass - Forage, Fodder and Hay include (1) Bermudagrass, (2) bluegrass3

and (3) bromegrass or fescue. In accordance with the Draft Grass Grown for Seed Policy (9/30/00), a total of eight (8) field trials should be perf ormed for a national registration on representative varieties (specifically , 3 trials in EPA Region 12, 2 trials in Region 11, and 3 trials in Region 5). A total of twelve (12) crop - field trials were conducted for grasses. Rye grass was added based on the s tatistical data that show ryegrass as being a major grass seed crop in the Pacific Northwest. Two (2) trials were conducted in Missouri (USEPA Region 5), one (1) trial in Minnesota (EPA Region 5), one (1) trial in Io wa (EPA Region 5), two (2) trials i n California (EPA Region 10), two (2) trials in Washington (EPA Region 11), and four (4) trials in Oregon (EPA Region 12). Trinexapac - eth yl250EC was applied to grasses grown for seed as a post foliar broadcast spray 35 day s prior to the harvest (swath) of mature seed and straw (49 days prior to harvest of regrowth forage and hay cutting) at a rate of 0.525 lb ai/A and 2 - 20 GPA (gallons per acre). The maximum residues were 5.7 ppm for grass straw, 20.0 ppm for grass seed screenings, 1.2 ppm for grass forage , and 3.4 ppm for grass hay . The limit of quantitation (L OQ) for CGA - 179500 is 0.01 ppm for all matrices. ii. Livestock. A livestock feeding study was conducted at three dosage levels, 2.0 ppm, 6.0 ppm, and 20 ppm. Residues of 0.03 ppm were found in the kidney at the 1X dose level all other tissues were <0.02 ppm (LOQ). No residues were detected in milk, LOQ 0.005 ppm. CGA - 179500 is the main metabolite of trinexapac - eth yl . A hen feeding study was also conducted. The hens were fed ad libitum for 28 day s w ith technical CGA 179500 at three levels

– nominally 3.3 ppm (1X), 9.9 ppm (3X), and 33.0 ppm (10X) in the feed on a dry

weight basis. Residues of 0.06 ppm were found in the kidney at the 1X dose level all other tissues were <0.01 ppm. No residues were det ected in eggs, LOQ 0.1 ppm. B. Toxicological Profile An assessment of toxic effects caused b y trinexapac - eth ylis discussed in the EPA assessment dated September 5, 2008, Trinexapac - Ethyl: Revised Human Health Assessment Scoping Document in Support of Registration Review . The technical trinexapac - ethyl product is classified in toxicity categories III & IV [CAUTI ON] based on acute oral, dermal, inhalation toxicity and eye/skin irritation studies. 1. Acute toxic ity. The acute toxicity data of trinexapac - eth ylshow that this chemical is low via the oral, inhalation and dermal routes of exposure (Categories III - IV ) and it is not a dermal sensitizer. 2. Genotoxicty. Mutagenicity s tudies indicate that trinexapac - eth yli s not mutagenic at doses tested. 3. Reproductive and developmental toxicity. Reproductive Toxicity : In a rat developmental toxicity

study there was an increased incidence of as ymmetrically shaped stern ebra. The developmental NOEL was ≥ 200 mg/kg and the Maternal Toxicity NOEL ≥ 1000 mg/kg. In a developmental toxicity study in New Zealand white rabbits, developmental toxicity4

was observed at 360 mg/kg and manifes ted as a decreased number of live fetuses per litter. Developmental NOEL = 60 mg/kg and the Developmental L OEL = 360 mg/kg. Maternal toxicity was not observed. A 2 - generation reproduction study in rats had a NOEL of 1000 ppm and a LOEL of 10,000 ppm based on reduced premating and gestation body weight and/or body weight gain. 4. Subchronic toxicity. Subchronic Oral Toxicity : A 13 - week rat feeding study had a NOEL of 500 ppm. A 13 - week dog feeding study had a NOEL of 15,000 ppm. A 21 - day dermal study

in rabbits had a NOEL of 10 mg/kg/day based on various biochemical parameters and microscopic observations of the skin. 5. Chronic toxicity. Chronic Oral T oxicity: In a combined oral oncogenicity/chronic study in rats, the LOEL for systemic toxicity = 10,000 ppm and the systemic toxicity NOEL = 3,000 ppm. Trinexapac - ethyl is not likely to be an oncogen. 6. Animal metabolism. The metabolism of cy prodinil in rats is adequatel y understood. As discussed in the EPA assessment dated September 5, 2008, Trinexapac Ethyl: Revised Human Health Assessment Scoping Document in Support of Registration Review , Trinexapac - eth yl is rapidly , extensively absorbed (both sexes) with >95% of the administered dose being absorbed. There is little potential for accumulation with >85% eliminated within 12 hours via urine and 2% via feces within 24 hours. There is very little or no biliary

excretion and no sex difference. The free aci d derivative resulting from hydrol ys is of the ester bond of parent compound is the major component in urine and feces. The onl y other component was parent which was found in the feces. 7. Metabolite toxicology . The residue of concern for tolerance settin g purposes is CGA - 179500. CGA - 179500 is the only animal metabolite of trinexapac - ethyl. Its toxicological properties are therefore fully assessed by

the animal studies performed with trinexapac - eth yl . Other metabolites are considered to be of equal or less er toxicity than the parent. 8. Endocrine disruption . An extensive toxicity database exists for trinexapac ethyl, including acute, subchronic, chronic, developmental, reproductive, and carcinogenicity

toxicology

studies. While no special studies have been conducted to investigate the potential for endocrine effects, the existing studies do not show evidence of compound - related endocrine - mediated effects or pathology of the endocrine organs. Consequently , it is concluded that trinexapac - eth yl does not possess endocrine disrupting properties. C. Aggregate Exposure 1. Dietary exposure. Acute (Tier I) and chroni c (Tier II) dietary exposure evaluations were made for trinexapac - ethyl using the Dietary Exposure Evaluation Model software with the Food Commodity Intake Database (DEEM - FCIDTM, version 2.16) from Exponent. All consumption data for these assessments were taken from the USDA’s Continuing Survey of Food Intake by individuals (CSFII) with the 1994 - 96 consumption database and the Supplemental CSFII children’s survey (1998) consumption database.5

These exposure assessments included all currentl y registered uses of trinexapac - eth yl plus the proposed foliar uses on wheat, barley , triticale, oats, grasses grown for seed and sugarcane. Residue data was taken from field trials where trinexapac - eth ylwas applied at the maximum intended use rate and samples were harvested at the minimum pre harvest interval (PHI) to obtain maximum residue values. Wheat residue data was used as a surrogate for barley

residue data. Anticipated residues in meat and milk were calculated b y constructing theoretical nutritionally balanced diets. Drinking water estimates were included directly into the dietary

exposure assessment using the higher of the estimated drinking water concentrations (EDWCs) for surface and ground water. i. Food. Acute exposure . The acute assessment was only performed for the females (13 - 49 years old) subpopulation as this subpopulation was the onl y one for which an acute endpoint was determined. The acute dietary risk assessment was performed with an acute reference dose (aRfD) of 0.6 mg/kg - bw/day based on an acute rabbit study with a no observed adverse effect level (NOAEL) of 60 mg/kg/day and an uncertainly

factor of 100X. The 100X safet y factor includes intra - and interspecies variations. No additional FQPA safety

factor was applied. The acute assessment was run using DEEM - FCIDTM software using proposed tolerance residue values and 100% CT values. For the purpose of the aggregate risk assessment, the exposure value was expressed in terms of margin of exp osure (MOE), which was calculated b y dividing the NOAEL b y the exposure for the females (13 - 49 years old) subgroup. In addition, exposure was expressed as a percent of the acute reference dose (% aRfD). Acute food exposure to the females (13 - 49 years old) subpopulation resulted in a MOE of 31,059 (0.3 % of the aRfD of 0.6 mg/kg - bw/day). Since the Benchmark MOE for this assessment was 100 and since the EPA generall y has no concern for exposures below 100% of the aRfD, Sy ngenta believes that there is a reason able certainty

that no harm will result from acute dietary (food) exposure to residues arising from the current and proposed uses for trinexapac - ethyl. Chronic exposure. The trinexapac - eth ylchronic dietary risk assessment was performed for all population subgroups with a chronic reference dose of 0.32 mg/kg/day based on a chronic dog stud y with a no observable adverse effect level (NOAEL) of 31.6 mg/kg/day and an uncertaint y factor of 100X. The 100X uncertainty factor includes a 100X safet y factor for intra - and inter - species variations. No additional FQPA safet y factor was applied. For the purpose of aggregate risk assessment, the exposure values were expressed in terms of margin of exposure (MOE), which was calculated b y dividing the NOAEL b y the exposur e for each population subgroup. In addition, exposure was expressed as a percent of the reference dose (% cRfD). Chronic dietary (food only) exposure to the U.S. population resulted in a MOE of 659,434 (0.0% of the chronic RfD of 0.32 mg/kg/day). The most sensitive sub - population was children (1 - 2 years old) with a MOE of 210,671 (0.0% of the chronic RfD of 0.32 mg/kg/day). Since the benchmark MOE for this assessment is 1,000 and since the EPA generall y has no concern for exposures below 100% of the RfD, Sy ngenta believes that there is a reasonable certainty that no harm will result from dietary (food onl y) exposure to residues arising from the current and proposed uses of trinexapac - eth yl . Cancer. No cancer risk assessment was performed for trinexapac - eth yl .6

ii. Drinking water. The EPA uses FIRST (FQPA Index Reservoir Screening Tool) as a Tier I screening model to estimate pesticide concentrations in surface water, and SCI GROW (Screening Concentration In Ground Water) as a Tier I screening model to estimate pesticide concentrations in ground water. These models do not consider the impact that processing (mixing, dilution, or treatment) would have on the removal of pesticides from the water source prior to distribution as drinking water. The primary use of these models is to provide a conservative approximation of the Estimated Drinking Wate r Concentrations (EDWCs) of specific pesticides in drinking water. These models were used b y S yn genta to calculate the highest EDWCs for trinexapac - ethyl from existing uses on turf and ry egrass grown for seed as well as proposed uses on wheat, barley , and sugarcane. Maximum EDWCs were calculated based on the turf use (4 applications x 0.6875 lb ai/A, 56 day interval). For surface water the peak (acute) EDWC for the combined residue of trinexapac - ethyl and its free acid degradate (CGA 179500) is estimated to be 49.725 ppb, and the annual average (chronic) EDWC is estimated to be 1.909 ppb. For ground water the EDWC is estimated to be 0.0130 ppb. Since the surface water EDWCs exceed the ground water EDWC, the surface water values should be used for comparison purposes and are considered protective for any ground water concentration concerns Acute Exposure from Drinking W ater : The acute EDWC of 49.725 ppb was used to calculate the acute drinking water exposure values for the females (13 - 49 years old) subpopulat ion as this subpopulation was the only one for which an acute endpoint was determined. Acute drinking water exposure to for the females (13 - 49 years old) subpopulation resulted in a MOE of 33,426 (0.3% of the aRfD of 0.6 mg/kg/day ; Benchmark MOE = 100). Si nce the Benchmark MOE for this assessment is 100 and since EPA generally

has no concern for exposures below 100% of the aRfD, Sy ngenta believes that there is a reasonable certaint y that no harm will result from acute drinking water exposure to residues ari sing from the current and proposed uses for trinexapac - eth yl . Chronic Exposure from Drinking W ater : The chronic EDWC of 1.909 ppb was used to calculate the chronic drinking water exposure values for the U.S. Population and population subgroups. Chronic drinking water exposure to the U.S. Population resulted in a MOE of 785,346 (or <0.01% of the cRfD of 0.32 mg/kg/day); Benchmark MOE = 100). The most sensitive sub - population was infants (<1 ye ar old) with a MOE of 239,543 (<0.01% of the cRfD of 0.32 mg/kg/ day ; Benchmark MOE = 100). Since the Benchmark MOE for this assessment is 100 and since EPA generall y has no concern for exposures below 100% of the cRfD, S yn genta believes that there is a reasonable certainty that no harm will result from chronic dietary (drinking water) exposure to residues arising from the current and proposed uses for trinexapac - ethyl. 2. Non - dietary exposure . A residential exposure and risk assessment was performed for trinexapac - eth ylusing the endpoints and uncertainty factors estab lished by the EPA in a recent assessment (September 5, 2008). Residential exposure and risk assessments were performed for trinexapac - ethyl uses on turf at the maximum single application rate of 0.88 lb ai/A. Trinexapac - ethyl is registered for non - food use s by homeowners and7

professional applicators on turf grasses. As such, residential assessments included handler exposure for adults and post - application exposure risks for adults and children. The highest predicted exposure for adults mixing, loading and appl yi ng product by belly grinder application to turf resulted in a combined (dermal plus inhalation) short - term margin of exposure (MOE) of 1,092. The post - application dermal exposure to adults, following use of granules on lawns, from high contact activity is MOE = 325. Children’s post application dermal plus non - dietary oral aggregate exposure to trinexapac - eth yl from lawn products had a short - term MOE of 225. Incidental ingestion of granules on treated lawns b y children , calculated based on the short - term incidental oral NOAEL (no acute endpoint identified), had a MOE of 9,736. Direct ingestion of granules is not aggregated with other routes of exposure for children because it is considered to be a one - time episodic event. The MOEs for all residential scenarios do not exceed the EPA’s level of concern (Benchmark MOE of 100) and there is a reasonable certainty that no harm will result from the residential uses of trinexapac - eth yl . D. Cumulative Effects Cumulative Exposure to Substances with a Common Mechanism of Toxicity. Section 408(b)(2)(D)(v) requires that, when considering whether to establish, modify , or revoke a tolerance, the Agency

consider “available information” concerning the cumulative effects of a particular pesticide’s residues and “other substances that have a common mechanism of toxicity”. The EPA does not have, at this time, available data to determine whether trinexapac - eth ylhas a common mechanism of toxicity with other substances or how to include this pesticide in a cumulative risk assessment. For the purposes of this tolerance action, the EPA has not assumed that trinexapac - eth ylhas a common mechanism of toxicity

with other substances. E. Safety Determination 1. U.S. population. T he chronic dietary exposure analy sis (food plus drinking water) showed that exposure from all established and proposed uses of trinexapac - ethyl result in a MOE of 358,452 (<0.1% of the chronic RfD of 0.32 mg/kg/day) for the general U.S. population. A short - term aggregate exposure anal ysis (food, water and residential) was required for adults because there are residential post - application exposure scenarios. The corresponding MOEs were aggregated using the inverse MOE approach. For short - t erm exposures the dietary

(food plus drinking water) exposure was aggregated with the residential exposure resulting in a short - term aggregate MOE o 325 for the adults (20 - 49 ye ars old). An intermediate - term aggregate exposure anal ys is (food, water and res idential) was not required for adults because residential lawn applications scenarios are not expected to occur for longer than a short - term time frame. Since the worst - case aggregate MOE of 325 exceeds the benchmark MOE of 100, Sy ngenta believes that ther e is a reasonable certaint y that no harm will result from aggregate exposure to residues arising from all current and proposed trinexapac - ethyl uses, including anticipated dietary exposure from food, water, and all other ty pes of non - occupational exposures . 2. Infants and children . The chronic dietary exposure anal ys is (food plus drinking water)8

showed that exposure from all established and proposed uses of trinexapac - ethyl result in a MOE of 150,657 (0.1% of the chronic RfD of 0.32 mg/kg/day) for the most sensitive population subgroup, children (1 - 2 years old). A short - term aggregate exposure ana ly sis (food, water and residential) was required for toddlers because there are residential post application dermal and oral exposure scenarios. The corresponding MOEs were aggregated using the inverse MOE approach. For short - term exposures, the dietary (f ood plus drinking water) exposure was aggregated with the residential exposure resulting in a short - term aggregate MOE of 225 for children (1 - 6 years old). An intermediate - term aggregate exposure anal ysis (food, drinking water and residential) was not requ ired for children because residential lawn applications scenarios are not expected to occur for longer than a short - term time frame. Since the worst - case aggregate MOE of 225 exceeds the benchmark MOE of 100, Sy ngenta believes that there is a reasonable ce rtaint y that no harm will occur to infants and children from aggregate exposure to residues arising from all current and proposed trinexapac - eth yluses, including anticipated dietary

exposure from food, water and all other ty pes of non - occupational exposur es. F. International Tolerances There are no Codex maximum residue levels (MRLs) established for residues of trinexapac - eth ylin or on grasses grown for seed. Codex MRL s have been established for sugarcane, rape, and cereal crops and in animal commoditie s including milk and beef kidney .