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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

[Insert petition number]

EPA has received a pesticide petition ([insert petition number]) from Syngenta 

Crop Protection, LLC, P.O. Box 18300, Greensboro, NC 27419-8300 requesting, 

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 0.02 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. 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 greater 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 these 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, "Residue Analytical 

Method for the Determination of Residues of Mesotrione and 4-(Methylsulfonyl)-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-Remove]

2. Genotoxicty. [NA-Remove]

3. Reproductive and developmental toxicity. [NA-Remove]

4. Subchronic toxicity. [NA-Remove]

5. Chronic toxicity. [NA-Remove]

6. Animal metabolism. [NA-Remove]

7. Metabolite toxicology. [NA-Remove]

8. Endocrine disruption. [NA-Remove]

C. Aggregate Exposure

1. Dietary exposure. A Tier II chronic dietary exposure evaluation was completed 

for mesotrione using the Dietary Exposure Evaluation Model (DEEM-FCIDTM), 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 dietary 
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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) 

consumption 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 all population subgroups with a chronic reference dose of 0.007 mg/kgbw/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 dividing 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 subpopulation 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 the 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 carcinogen”. 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 water 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 surface 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 software 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 exposure to the most exposed sub-population 
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(all infants, <1 year old) resulted in a MOE of 5,959 (5.0% of the cRfD of 0.007 mg/kgbw/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 weeds 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 potential postapplication 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 days) 

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 longterm exposures (greater than six months) are not expected. Therefore, intermediate-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./ft2

) per 

application of TenacityTM, 0.19% Mesotrione 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./ft2

) per application of 0.08% Mesotrione 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 calculated 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 were calculated for Mesotrione using the calculated TTR value 

of 0.0056 μg/cm2

. 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 of 
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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/cm2. 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 11-16 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 mesotrione 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 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 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 substances.

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. population. 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, pending 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 mesotrione uses, including anticipated dietary 

exposure from food, water and all other types of non-occupational exposures.
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F. International Tolerances

There are currently no Maximum Residue Limits (MRLs) set for mesotrione for 

crops by the Codex Alimentarius Commission. 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.