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EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER

EPA Registration Division contact: Ms. Kathryn Montague, 703

- 305

- 1243

TEMPLATE:

Syngenta Crop Protection, LLC

[In sert petition number]

EPA has received a pesticide petition ( [insert petition number] ) from Syngenta Crop Protection, LLC

, P.O. Box 18300, Greensboro, NC 27419

- 8300 request ing, 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 mesotrione in or on the raw agricultural commodity soybean at 0.0 2 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 nee ded before EPA rules on the petition.

A. Residue Chemistry

1. Plant metabolism. The nature of mesotrione residues is well understood for corn. Mesotrione is rapidly and completely metabolized in corn. No single extract or component accounted for grea ter than 0.01 ppm in grain. Numberous components were characterized in forage and fodder, including the metabolite 2

- amino

- 4

- methylsulfonyl benzoic acid (AMBA) and its conjugates and 4

- methylsulfonyl

- 2

- nitrobenzoic acid (MNBA). EPA has determined that th ese two metabolites are not toxicologically significant and are not included in the tolerance expression or in the mesotrione risk assessments. Two additional metabolite studies, cranberries and peanuts, have also been submitted for cranberry and peanut. The results are similar to corn and the metabolism is considered understood for all crops, per EPA Test Guideline 860.1300. A tolerance was subsequently established at 0.01 ppm for certain soybean varieties with natural soybean tolerance. This petition is to amend the tolerance based on studies conducted with a new HPPD tolerant soybean. The metabolic pathway determined for these soybean plants is similar to that observed in previous crops tested.

2. Analytical method. [ Syngenta Method RAM 366/01, "R esidue Analytical Method for the Determination of Residues of Mesotrione and 4

- (Met hylsulfonyl)

- 2

-2

Nitrobenzoic Acid (MNBA) in Crop Samples" (MRID 45651803) with modifications was used for the analysis of soybeans. The method Limit of Quantitation (LOQ) was 0.01 ppm for mesotrione and its metabolite, MNBA.

3. Magnitude of residues. [Insert text.]

B. Toxicological Profile 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. The nature of the toxic effects caused by mesotrione as well as the no observed adverse effect level (NOAEL) and the lowest observed adverse effect level (LOAEL) from the toxicity studies reviewed are discussed in the Federal Register of June 21, 2001 (66 FR 33187) (FRL

- 67877). A summary of the toxicological endpoints for mesotrione used for human risk assessment is discussed in Unit III.B of the final rule published in the Federal Register of June 21, 2001. The data was reviewed and more recently discussed in Unit III of the final rule published in the Federal Register of February 20, 2008 in support of newly approved minor uses.

1. Acute toxicity. [ NA

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2. Genotoxicty. [ NA

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3. Reproductive and developmental toxicity. [ NA

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4. Subchronic toxicity. [ NA

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5. Chro nic toxicity. [ NA

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6. Animal metabolism. [ NA

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7. Metabolite toxicology

. [ NA

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8. Endocrine disruption

. [ NA

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C. Aggregate Exposure

1. Dietary exposure. A Tier II chronic dietary exposure evaluation was completed for mesot rione using the Dietary Exposure Evaluation Model (DEEM

- FCID TM ), version 2.14 from Exponent. In addition to all currently registered uses of mesotrione (asparagus, berry Crop Group (Crop Group 13), field corn, sweet corn, popcorn , cranberry, flax,
grasses grown for seed, millet, oat, okra, rhubarb, sorghum, and sugarcane), and the pending reinstatement of aerial applications for corn and sugarcane, this exposure assessment included a proposed use on herbicide (mesotrione) tolerant soybeans (HT soybeans)

. Percent of crop treated values were conservatively estimated to be 100% for the proposed use. Drinking water estimates were incorporated directly into the dietary3

exposure assessment using the higher of the estimated drinking water concentrations (EDWCs) for surface and ground water. All consumption data for these assessments was 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) consumptio n database.

i. Food. Acute Exposure. Mesotrione is not considered to be acutely toxic and an acute toxicological endpoint was not selected by the Agency.

Chronic Exposure. The mesotrione chronic dietary (food only) risk assessment was performed for al l population subgroups with a chronic reference dose of 0.007 mg/kg

bw/day based on a mouse reproduction study with a Lowest Observable Adverse Effect Level (LOAEL) of 2.1 mg/kg

- bw/day and an uncertainty factor of 300X. The 300

- fold safety factor includes intra

- and interspecies variations (100X) and an additional FQPA safety factor of 3X (absence of NOAEL). For the purpose of the aggregate risk assessment, exposure values were expressed in terms of margin of exposure (MOE), which was calculated by dividi ng the LOAEL by the exposure for each population subgroup. In addition, exposure was also expressed as a percent of the reference dose (%RfD). Chronic (food only) exposure to the U.S. population resulted in a MOE of 131,811 (0.2% of the chronic RfD of 0. 007 mg/kg

- bw/day). The most sensitive sub

population was children (3

- 5 years old) with a MOE of 55,097 (0.5% of the chronic RfD). Since the benchmark MOE for this assessment was 300 and since the EPA generally has no concern for exposures below 100% of t he RfD, Syngenta believes that there is a reasonable certainty that no harm will result from dietary (food only) exposure to residues arising from the current and proposed uses for mesotrione.

Cancer

. Mesotrione is considered “not likely to be a human ca rcinogen”. Therefore, no cancer risk assessment was performed for mesotrione

.

ii. Drinking water

. The Estimated Drinking Water Concentrations (EDWCs) of mesotrione were determined using Tier l SCI

- GROW which estimates pesticide concentration in ground w ater and Tier II PRZM/EXAMS which estimates pesticide concentration in surface water. Currently registered uses plus the proposed use on HT soybeans were assessed. Based on the SCI

- GROW modeling, the groundwater EDWC for mesotrione is 0.54 ppb (chronic) based on the currently registered use Experimental Use Permit (EUP) on soybeans. Based on Tier II PRZM/EXAMS modeling for surface water, the soybean EUP provided a chronic EDWC of 5.1 ppb. Since the surface water EDWC exceeds the ground water EDWC, the s urface water value was used for risk assessment purposes and will be considered protective for any ground water exposure

concerns.
Chronic Exposure from Drinking Water

. The chronic surface water EDWC of 5.1 ppb was input directly into the DEEM

- FCIDTM so ftware as “water, direct and indirect, all sources” to model the chronic drinking water exposures. Chronic drinking water exposure to the U.S. population resulted in a MOE of 19,536 (1.5% of the cRfD of 0.007 mg/kg

- bw/day). Chronic drinking water exposur e to the most exposed sub

- population4

(all infants, <1 year old) resulted in a MOE of 5,959 (5.0% of the cRfD of 0.007 mg/kg

bw/day). Since the Benchmark MOE for this assessment was 100 and since EPA generally has no concern for exposures below 100% of the cRfD, Syngenta believes that there is a reasonable certainty that no harm will result from chronic drinking water exposure to residues arising from the current and proposed uses for mesotrione

.

2. Non

- dietary exposure

. Currently the herbicide containing mesotrione is formulated as a liquid and marketed under the trade name TenacityTM, 0.08% Mesotrione on Fertilizer, 0.19% Mesotrione on Fertilizer, and 0.25% Mesotrione on Fertilizer. These products are used for selective contact and residual control of we eds in turfgrasses for golf courses and sod farms. TenacityTM is labeled for use only by professional applicators; therefore, residential handler application scenarios were not assessed. Residential (non

- occupational) risk assessments were conducted for p otential post

application exposure to adults and youth on treated golf courses.

The post

- application exposures on treated golf courses include dermal exposures due to contact activities with the treated areas. Risks due to short

- term exposures (1

- 30 day s) were assessed using the Margin of Exposure (MOE) approach. Based on the use pattern of mesotrione on turf, intermediate

- term exposures (1 to 6 months) are unlikely and long

term exposures (greater than six months) are not expected. Therefore, intermed iate

- term and long

- term risks were not assessed.

Residential exposures were assessed assuming a one

- time maximum application rate of 0.25 pounds of active ingredient per acre (0.25 lb a.i./A or 5.74E

- 06 lbs a.i./ft 2 ) per application of TenacityTM, 0.19% Me sotrione on Fertilizer, and 0.25% Mesotrione on Fertilizer. Residential exposures were assessed assuming a one

- time maximum application rate of 0.15 pounds of active ingredient per acre (0.15 lb a.i./A or 3.44E

- 06 lbs a.i./ft 2 ) per application of 0.08% Me sotrione on Fertilizer. The absorbed dose was assumed to be 1% for dermal exposure. Dermal risks were assessed against a lowest observed adverse effect level (LOAEL) of 2.1 mg/kg/day from a mouse reproduction study. Residential handler risks were calcu lated for granular application of Mesotrione. The short

- term MOEs were 8,129 (Granular Open Pour Belly Grinder Loader Applicator) and 164,815 (Push Spreader Loader Applicator). Since the calculated residential hander exposures were found to be well above the EPA’s level of concern (MOEs>300), there are acceptable residential handler risks from applications of mesotrione products to turf.

Post application dermal exposure risks for adults and youths due to physical activities on turf, mowing, and golfing w ere calculated for Mesotrione using the calculated TTR value of 0.0056 μg/cm 2 . The short

- term MOEs for high contact dermal exposure resulting from activities on turf were 9,983 (adults 26

- 81 years old), and 5,084 (children 1

- 2 years old). The short

- term MOEs for mowing were 544,553 (adults 26

- 81 years old) and 474,215 (youths 11

- 16 years old). The short

- term MOEs for golfing were 141,276 (adults 26

- 81 years old), 121,248 (youths 11

- 16 years old), and 103,277 (youths 6

- 11 years old). Since the calculated post

- application exposures were found to be well above the EPA’s level of5

concern (MOEs>300), there are acceptable post

- application risks to adults and youth from applications of mesotrione products to golf courses.

Post

- application dermal exposure risks for adults and youths due to physical activities on turf, mowing, and golfing were calculated for TenacityTM using the calculated TTR value of 0.083 μg/cm 2 . The short

- term MOEs for high contact dermal exposure resulting from activities on turf were 2,219 (adults 26

- 81 years old), and 1,121 (children 1

- 2 years old). The short

- term MOEs for mowing were 108,911 (adults 26

- 81 years old) and 94,843 (youths 11

- 16 years old). The short

- term MOEs for golfing were 28,255 (adults 26

- 81 years old), 24,250 (youths 1 1

- 16 years old), and 20,655 (youths 6

- 11 years old). Since the calculated post

- application exposures were found to be well above the EPA’s level of concern (MOEs>300), there are acceptable post

- application risks to adults and youth from applications of me sotrione products to golf courses.

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 cons ider “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 mesotrione has 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 mesotrione has a common mechanism of toxicity with other substance s.

E. Safety Determination

1. U.S. population. The chronic dietary exposure analysis (food plus water) showed that exposure from all registered and proposed mesotrione crop uses result in a MOE of 17,213 (1.74% of the chronic RfD) for the general U.S. p opulation. Based on the completeness and reliability of the toxicity data supporting these petitions, Syngenta believes that there is a reasonable certainty that no harm will result from aggregate exposure to residues arising from all current and proposed mesotrione uses, including anticipated dietary exposure from food, water, and all other types of non

- occupational
exposures.

2. Infants and children

. The chronic dietary exposure analysis (food plus water) showed that exposure from all registered, pendi ng and proposed mesotrione uses would result in a MOE of 5,551 (5.4% of the chronic RfD) for infants less than one year old (the most sensitive population subgroup). A short

- term aggregate MOE of 355 (LOC = 300) was determined for children (1

- 6 years old)

. Since all aggregate MOEs exceed the benchmark MOE of 300, Syngenta believes that there is a reasonable certainty that no harm will occur to infants and children from aggregate exposure to residues arising from all current, pending, and proposed mesotrio ne uses, including anticipated dietary exposure from food, water and all other types of non

- occupational exposures

.6

F. International Tolerances

There are currently no Maximum Residue Limits (MRLs) set for mesotrione for crops by the Codex Alimentarius C ommission. International MRLs for the herbicide mesotrione have been established for various agricultural commodities in a number of countries including Argentina, Austria, Belgium, Brazil, Czech Republic, Denmark, France, Germany, Greece, Hungary, Italy, Luxembourg, Morocco, Netherlands, Serbia and Montenegro, Slovak Republic, Slovenia, South Africa, and the United States.