Alexander B. GrannisCommissioner

New York State Department of Environmental ConservationDivision of Solid and Hazardous MaterialsBureau of Pesticides Management, 11th Floor

625 Broadway, Albany, New York 12233-7254

Phone: (518) 402-8788 • FAX: (518) 402-9024

Website: www.dec.ny.gov

September 4, 2008

CERTIFIED MAILRETURN RECEIPT REQUESTED

Ms. Susan PersonRegulatory AssistantSyngenta Crop Protection, Inc.P.O. Box 18300 Greensboro, North Carolina 27419-8300

Dear Ms. Person:

Re: Registration of a Major Change in Labeled (MCL) Use Pattern for theActive Ingredient Mesotrione Contained in the Pesticide Product Tenacity (EPA Reg. No.TM

100-1267)

The New York State Department of Environmental Conservation (Department)completed a technical review of the application (received February 19, 2008) and supplementalinformation (received June 9, 2008) submitted in support of registration of the referencedpesticide product. Tenacity (EPA Reg. No. 100-1267) contains the active ingredientTM

mesotrione (Chemical Code 122990).

Tenacity (40.0% mesotrione) is a systemic preemergence and post-emergence herbicideTM

for the selective contact and residual control of weeds in turfgrasses on golf courses and sodfarms. On December 12, 2007, the United States Environmental Protection Agency (USEPA)issued a reduced-risk decision for the turf (sod farm, golf courses) uses of the conventionalpesticide mesotrione: http://www.epa.gov/opprd001/workplan/completionsportrait.pdf.

Mesotrione is a component of a number of products currently registered in New YorkState for use on field corn, production seed field corn, field corn grown for silage, yellowpopcorn, and sweet corn. The proposed use on turf represents a major change in labeled (MCL)use pattern for mesotrione.

The subject application package was deemed complete for purposes of technical reviewon April 15, 2008. Pursuant to the review time frame specified in Environmental ConservationLaw (ECL) §33-0704.2, a registration decision date of September 12, 2008 was established.

Human health and environmental fate risk assessments were conducted for mesotrioneand the formulated product Tenacity . An ecological effects risk assessment was not available.TM

Ms. Susan Person 2.

HUMAN HEALTH RISK ASSESSMENT: The New York State Department of Health(NYSDOH) previously reviewed the new active ingredient mesotrione and the formulatedproduct Callisto Herbicide (EPA Reg. No. 100-1131) in 2002. Tenacity is a repackaging of® TM

the Callisto product for turf use. Neither mesotrione nor the formulated product Tenacity was® TM

very toxic in acute oral, dermal or inhalation exposure studies in laboratory animals. Mesotrionewas a moderate eye irritant, but not a skin irritant or sensitizer, whereas Tenacity was slightlyTM

irritating to both skin and eyes and a mild skin sensitizer. Mesotrione caused some toxicity insubchronic and chronic animal feeding studies, including ocular lesions, liver and kidney toxicityand increased plasma tyrosine levels. In addition, this chemical caused delayed ossification inoffspring of rats, mice and rabbits in developmental toxicity studies and was associated withsignificantly increased plasma tyrosine levels in a multigeneration reproduction studies in ratsand mice. Mesotrione did not cause oncogenic effects in rat or mouse chronic feeding studiesand was negative in a number of genotoxicity studies. Based on this, the USEPA classifiedmesotrione as “not likely to be carcinogenic to humans.” A current search of the toxicologicalliterature did not find any significant new information on the toxicity of mesotrione.

Mesotrione’s mode of action as an herbicide is through the inhibition of the enzyme p-hydroxyphenylpyruvate dioxygenase (HPPD) which is involved in carotenoid pigment synthesisthat protects chlorophyll from decomposition by sunlight. In mammals, HPPD is involved in thecatabolism of the amino acid tyrosine. The registrant conducted a series of studies todemonstrate that the spectrum of toxicological effects reported in the animal studies results fromelevated tyrosine levels in part caused by mesotrione’s inhibition of HPPD. These studies alsoindicated that another enzyme involved in tyrosine catabolism, tyrosine aminotransferase (TAT),accounts for species differences in tyrosine levels and, therefore, their sensitivity to mesotrione. Because TAT activity in humans and mice is relatively high compared to that of the rat,rendering them less sensitive to mesotrione-mediated effects, data from mouse studies arebelieved to be more suitable for assessing risks to humans than are rat data. The USEPA, Officeof Pesticide Programs, established a reference dose (RfD) of 0.007 milligrams per kilogram bodyweight per day (mg/kg/day) based on a lowest-observed-effect level (LOEL) of 2.1 mg/kg/day inthe mouse multigeneration reproduction study and an uncertainty factor of 300. An uncertaintyfactor of 100 was used to account for inter-species extrapolation and human variability and anadditional uncertainty factor of 3 to account for using a LOEL instead of a no-observed-effect-level (NOEL). This RfD has not yet been adopted by the USEPA’s Integrated Risk InformationSystem (IRIS).

The USEPA reported the results of a risk assessment for short-term (1-30 days) dermalpost-application exposures to mesotrione from use on golf course turf. An estimated four-hourdermal exposure from treated turf was assumed for an adult and child golfer. For determiningmargins of exposure (MOEs), the USEPA compared estimated short-term dermal exposures to aLOEL of 2.1 mg/kg/day from the multigeneration reproduction study in the mouse (tyrosinemiaand ocular discharge). The estimated short-term dermal MOEs for an adult and child golfer wereestimated to be 45,000 and 29,000, respectively. The USEPA considered a target MOE of 3,000to be adequately protective of human health for this exposure scenario. There are no residentialuses on the Tenacity label, so residential handler exposure and post-application exposure fromTM

treated residential turf were not assessed.

Ms. Susan Person 3.

The USEPA also reported the results of an occupational risk assessment for combinedshort- (1-30 days) and intermediate-term (1-6 months) dermal and inhalation exposures for themost highly exposed occupational handler scenarios. These handler scenarios includedmixer/loaders (aerial and groundboom applications), applicators (aerial and groundboomequipment) and flaggers (aerial applications) for liquid formulations such as the TenacityTM

product. For determining MOEs, the USEPA compared estimated combined short- andintermediate-term dermal and inhalation exposures to LOELs of 2.1 mg/kg/day from themultigeneration reproduction study in the mouse (tyrosinemia and ocular discharge) and100 mg/kg/day from the developmental toxicity study in rats (delays in skeletal ossification andchanges in hand/foot ossification assessments), respectively. For mixer/loaders, the MOEs fordermal exposures were estimated to be between 6,500 and 29,000; MOEs for inhalationexposures were between 60,000 and 260,000. For commercial applicators, the MOEs for dermalexposures were estimated to be between 30,000 and 47,000 and between 420,000 and 1,100,000for inhalation exposures, assuming an enclosed cockpit for aerial applications. The dermal andinhalation MOEs for flaggers supporting aerial applications were estimated to be 14,000 and200,000, respectively. These estimates assumed that all workers wore long-sleeved shirt andpants, chemical-resistant gloves, and shoes plus socks as per label requirements. MOEs for avariety of post-application activities (mowing, aerating, transplanting, etc.) on Day 0 of theapplication were estimated to be between 1,700 and 3,300. The USEPA considered MOEs of300-fold or greater to provide adequate worker protection from mesotrione.

There are no chemical specific federal or New York State drinking water/groundwaterstandards for mesotrione or its degradates. Based on their chemical structures, mesotrione and itsdegradates fall under the 50 microgram per liter (µg/L) New York State drinking water standardfor “unspecified organic contaminants” (10 NYCRR Part 5, Public Water Systems). TheNew York State drinking water standard for the sum of “unspecified organic contaminants” and“principal organic contaminants” is 100 µg/L. If one uses the chronic population adjusted dose(cPAD) derived for the general U.S. population (0.0007 mg/kg/day) and procedures for derivingambient water quality standards and guidelines based on non-oncogenic effects (6 NYCRR Part702.5), a value of 5 µg/L can be calculated. This value could be used to derive a screening valuefor comparison to estimated impacts to groundwater and surface water.

The NYSDOH concluded that the available information on mesotrione and TenacityTM

indicates that they are not very acutely toxic in laboratory animal studies. Data from animaldevelopmental and reproductive studies indicate that mesotrione affects offspring throughdelayed ossification and ocular effects. These effects, as well as those in the liver and kidney, arebelieved to be secondary to tyrosinemia that in part results from the inhibition of the enzymeHPPD. Although mesotrione has the potential to cause tyrosinemia, humans have a capacity toregulate tyrosine levels (due to a relatively high TAT activity level). In addition, the expectedexposure from the labeled use of Tenacity on sod farms and golf courses is rather low andTM

should not pose a significant risk to the general public or to workers. As with the previousreview of Callisto Herbicide, NYSDOH continues to have some concern about the leaching®

potential of mesotrione and its degradates (MNBA and AMBA) to contaminate groundwater anddrinking water. While these concerns may be somewhat offset by the relatively low applicationrate of Tenacity , NYSDOH recommended that the Department consider whether mitigativeTM

measures (e.g., prohibiting its use in vulnerable areas of the State) are necessary before making afinal decision on registration of this product in New York State.

Ms. Susan Person 4.

ENVIRONMENTAL FATE RISK ASSESSMENT: Syngenta Crop Protection, Inc., isapplying to register Tenacity for use as a pre- and post-emergent herbicide for selective contactTM

and residual control of weeds in turf grasses on golf courses and sod farms. The product contains40% by weight active ingredient or 4 lbs per gallon active ingredient (ai), and the maximumapplication rate is 0.5 lb ai/acre/year.

Mesotrione is currently registered for use in New York State on field corn, productionseed field corn, field corn grown for silage, yellow popcorn and sweet corn at a maximumapplication rate of 0.34 lb ai/a/year.

Mesotrione is a reduced risk pesticide and belongs to the class of chemicals calledtriketones. It inhibits amino acid conversion and carotenoid biosynthesis which results in theplant not protecting the chlorophyl from decomposition by sunlight. It provides effective controlof triazine, sulfonylurea and other ALS resistant weeds.

Solubility: Mesotrione has a solubility of 160 ppm.

Hydrolysis: (MRID 44373529) This study was found to be acceptable by the USEPA. Mesotrione was found to be stable at pHs 5, 7, and 9.

Aqueous Photolysis: (MRID 44537108) This study was found to be acceptable by the USEPA. The phenyl ring-labeled [ C] mesotrione degraded with a half-life of 86.8 days. The14

cyclohexane ring-labeled [2- C] mesotrione degraded with a half-life of 80.5 days. 14

Soil Photolysis: (MRIDs 44505128 and 45196005) This study and addendum were found to besupplemental by the USEPA, however, the Agency did not request any additional data becausesoil photolysis data was not critical to the fate assessment. The registrant-calculated half-lives ofthe parent were questionable. MNBA accounted for up to 12% of parent and AMBA up to 9%.

Aerobic Soil Metabolism: This study (MRIDs 44373530 and 44505130 addendum) was foundto be acceptable and partially satisfied the data requirements of the USEPA. However, incombination with other studies, the data requirements for aerobic soil metabolism are satisfied. The cyclohexane ring-labeled [2- C] mesotrione degraded with a half-life of 13.5 days; however,14

USEPA did have comments about the way the study was conducted which may have affected thehalf-life. No degradates were mentioned in this study.

Another study (MRID 4437351) was found to be acceptable and partially satisfied the datarequirements of the USEPA. However, in combination with other studies, data requirements foraerobic soil metabolism are satisfied. The apparent half-life is open to interpretation and leavesuncertain the nature and identity of some transformation products. MNBA accounted for 7.6% ofapplied and AMBA accounted for up to 9.7% of applied.

Another study (MRID 45196006) showed a half-life of approximately 18 days.

Another study (MRID 44505208) was found to be acceptable and partially satisfied the data

Ms. Susan Person 5.

requirements of the USEPA. However, in combination with other studies, data requirements foraerobic soil metabolism are satisfied. Three soils were studied; a sandy loam from the U.S., aloam from France and a clay loam from England. However, USEPA had concerns that theextraction method was inadequate. The phenyl ring-labeled [ C] mesotrione degraded with a14

half-life of 12 days in sandy loam, 5.9 days in loam and 4.6 days in clay loam. In the sandy loamsoil, MNBA accounted for 12.7% of applied and AMBA accounted for up to 4.2% of applied. Inthe loam soil, MNBA accounted for 46.8% of applied. In the clay loam soil, MNBA accountedfor 4.7% of applied and AMBA accounted for up to 4.2% of applied.

Anaerobic Aquatic Metabolism: This study (MRID 44505131) was found to be acceptable andpartially satisfied the data requirements of the USEPA. The phenyl ring-labeled [ C] mesotrione14

degraded with a reviewer calculated half-life of 3.9 days in a flooded silt loam. AMBA in theaqueous phase was 66%. In the soil phase, AMBA was 49%.

Another study (MRID 44505132) was found to be acceptable and partially satisfied the datarequirements of the USEPA. The cyclohexane ring-labeled [2- C] mesotrione degraded with a14

half-life of 4.2 days in a flooded silt loam. There was one major unidentified degradate in thisstudy.

Parent Adsorption/Desorption: This study (MRID 44505203), in combination with otheradsorption/desorption studies, was found to be acceptable by the USEPA. Mesotrione had an

ocadsorption K of 58 in sandy loam, 19 in loam, 48 in silt loam, and 29 in clay loam. Mesotrione

ochad a desorption K of 130 in sandy loam, 33 in loam, 61 in silt loam, and 50 in clay loam.

Another study (MRID 44373532), in combination with other adsorption/desorption studies, was

ocfound to be acceptable by the USEPA. Mesotrione had a adsorption K of 47 in silt loam, 25 insandy loam, 171 in silty clay loam, 70 in clay and 14 in loam soil. Mesotrione had a desorption

ocK of 67 in silt loam, 56 in sandy loam, 198 in silty clay loam, 86 in clay and 32 in loam soil.

Degradate Adsorption/Desorption: For MNBA, the study (MRID 44505201) was found to be

ocacceptable by the USEPA. MNBA had a adsorption K of 3.2 in silt loam, and 6.1 in silty clayloam; estimated values were less than 20 in the sandy loam, 6 in clay and 10 in loam soils.

ocMNBA had a desorption K of 13.3 in silt loam, and 15.6 in silty clay loam; estimated valueswere less than 20 in the sandy loam, clay and loam soils.

Study (MRID 44505202) was found to be acceptable by the USEPA. AMBA had a adsorption

ocK of 44.9 in silt loam, 22.7 in sandy loam, 122.1 in silty clay loam, and 51 in clay soil and

oc17.7 in loam soil. AMBA had a desorption K of 68.9 in silt loam, 37.9 in sandy loam, 155.9 insilty clay loam, and 109.3 in clay soil and 50.2 in loam soil.

Field Dissipation: Two studies (MRIDs 44505206 and 44505207) were found to besupplemental by the USEPA. “Although parent mesotrione “disappeared” fairly rapidly, 1) nodegradates, including MNBA and AMBA which were found in laboratory studies, were detectedat any sampling interval, and 2) mesotrione was not observed to leach. Furthermore, becausethere was no water balance during the study (or even pan evaporation data), it could not bedetermined if and when conditions were favorable for leaching and whether potential leached

Ms. Susan Person 6.

amounts of parent or degradates could have escaped detection by leaching below the maximumdepth sampled during the time between sampling intervals and/or by insufficiently low detectionlimits in the sampled soil profile. This study presents an unresolved account of the terrestrialfield dissipation of mesotrione.”

Degradate Field Dissipation: This study (MRID 44901714) was found to be acceptable andpartially satisfied the data requirements of the USEPA. The half-life of AMBA wasapproximately 16 days in clay soil (English soil), 27 days in silt loam soil (Wisconsin), and20 days in sandy loam soil (English soil).

Surface Water Advisory: The label contains a surface water advisory that addresses drift,runoff, poorly draining soils and erosion controls. A groundwater advisory was discussedbetween USEPA and the registrant, but was not required for the final label.

Prospective Groundwater Monitoring Study: The registrant conducted a Small Scale PGWstudy on corn in North Carolina. Mesotrione, MNBA and AMBA were only detected above theLOQ in soil pore water at the 3 foot depth. Detections were found at four of the eight 3-footlysimeters, with no detections after 3.5 months after treatment. Peak parent concentrations at onelysimeter reached 11 ppb and at the others were < 2 ppb with degradate concentrations< 0.58 ppb. No detections of parent or degradates were found at any deeper lysimeters or ingroundwater throughout the 30 month study. USEPA feels that the clear pattern of increase anddecline at the 3-foot lysimeters suggests that the compound reaches this depth and dissipatesthrough regular sorption and degradation processes rather than through preferential flow or arapid initial pulse following a precipitation event. The lack of detection at deeper locations, then,can be interpreted as evidence that leaching is not expected, rather than of insufficient samplingtime.

ocComputer Modeling: Mesotrione was modeled using Riverhead sandy soil, a K of 130, ahalf-life of 18 days and an application rate of 0.5 lb ai/a/yr. The model projected cyclic peaks of0.005 to 0.025 ppb. MNBA was not modeled because no half-life was given in theenvironmental fate data. In studies that were considered inadequate, USEPA indicated a range ofone day to several months. However, the studies also indicate that MNBA breaks down intoAMBA, so AMBA was modeled. Staff modeled AMBA separately, assuming 50% ofmesotrione breaks down into MNBA, then 25% of MNBA breaks down to AMBA. Staff used a

ocK of 38 for AMBA, a half-life of 20 days, and assumed 25% of the maximum application rate(0.06 lb ai/a). The model projected cyclic peaks of about 0.1 to 0.4 ppb.

ocEnvironmental Fate Summary: Even though mesotrione has a low K and is consideredmobile, it will probably not leach significantly to groundwater on sandy Long Island soils whenused as labeled because of the very short half-life and low application rate. Modeling resultssupport this determination.

REGISTRATION ACTION: When used as labeled, the subject product should not causeunreasonable adverse effects to humans or the environment. The Department hereby acceptsTenacity (EPA Reg. No. 100-1267) for registration in New York. Enclosed for your filesTM

are the Certificate of Pesticide Registration and New York State stamped “ACCEPTED” labeling

Ms. Susan Person 7.

(coded SCP 1267A-L1 1207).

Please note that a proposal by Syngenta Crop Protection or any other registrant to registera product containing mesotrione, whose labeled uses are likely to increase the potential forsignificant exposure to humans, nontarget organisms or the environment, would constitute amajor change in labeled (MCL) use pattern. Such an application must be accompanied by a newapplication fee and meet the requirements specified in 6 NYCRR Part 326.17.

Please contact our Pesticide Product Registration Section, at (518) 402-8768, if you haveany questions.

Sincerely,

Maureen P. Serafini

Maureen P. SerafiniDirectorBureau of Pesticides Management

Enclosures

ecc: A. Grey/E. Horn, NYS Dept. of HealthR. Mungari, NYS Dept. of Ag. & MarketsW. Smith, Cornell University, PSUR