May 22, Ms. Susan Person Syngenta Crop Protection, Inc. 410 South Swing Road Greensboro, NC Dear Ms. Person:

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1 New York State Department of Environmental Conservation Division of Materials Management Bureau of Pest Management Product Registration & Pest Management Alternatives Section 625 Broadway, Albany, New York Phone: (518) Fax: (518) Website: Joe Martens Commissioner May 22, 2013 Ms. Susan Person Syngenta Crop Protection, Inc. 410 South Swing Road Greensboro, NC Dear Ms. Person: Re: Registration of a Major Change in Labeling for the Active Ingredient Trinexapac-ethyl as Contained in Palisade 2EC (EPA Reg. No ) The New York State Department of Environmental Conservation (Department) has evaluated your application, received March 1, 2012, and supplemental materials received to date in support of the registration of a major change in labeling for the active ingredient trinexapacethyl. Trinexapac-ethyl was first registered in New York State on March 17, 1994 for use on commercial and residential turf. Turfgrass products containing trinexapac-ethyl were classified as restricted use due to concerns related to groundwater impacts. Palisade 2EC contains 25.5% of the active ingredient trinexapac-ethyl and is formulated as an emulsifiable concentrate. It is labeled for growth management of wheat, barley, sugarcane, and grasses grown for seed. The Department determined that the proposal to apply trinexapac-ethyl on food crops constitutes a major change in labeling in New York State. The Palisade 2EC product label allows application via ground, aerial, and chemigation methods. The maximum application rates are 0.11 pounds of trinexapac-ethyl per acre per year for cereals and 0.50 pounds of trinexapac-ethyl per acre per year for grasses grown for seed. The application package was deemed complete for purposes of technical review on February 7, Pursuant to the review time frame specified in Environmental Conservation Law , a registration decision date of July 5, 2013 was established. Technical reviews of the proposed use included in the Palisade 2EC label have been performed by the Department and the New York State Department of Health. These reviews encompassed the expected impacts of labeled use of the subject product with respect to human health, ecological effects, and environmental fate. The technical reviews are shown below.

2 Ms. Susan Person 2. HUMAN HEALTH ASSESSMENT: The following assessment was prepared by staff within the Bureau of Toxic Substance Assessment at the New York State Department of Health (DOH). Neither the formulated product nor the active ingredient was very toxic on an acute basis to laboratory animals by the oral, dermal or inhalation routes of exposure. The formulated end product was moderately irritating to the eyes and skin, whereas the active ingredient was only slightly irritating to the eyes and moderately irritating to the skin (tested on rabbits). Palisade 2EC was found to be a dermal sensitizer, however the active ingredient was not (tested on guinea pigs). Trinexapac-ethyl did not cause oncogenic effects in either rat or mouse chronic feeding studies and was negative in a number of genotoxicity studies. Based on these results, the U.S. Environmental Protection Agency (U.S. EPA) classified trinexapac-ethyl as not likely to be carcinogenic to humans. Trinexapac-ethyl caused some toxicity (diffuse thymic atrophy, changes in the epithelial cells of the renal tubules and brain lesions) in subchronic and chronic toxicity studies in dogs. This active ingredient also caused some developmental/reproductive toxicity, at doses that did not elicit maternal effects, in rats (increased incidence of asymmetrical sternebrae) and rabbits (decreased number of fetuses per litter and increased post-implantation loss). In addition, parental (decreased bodyweight and/or body weight gain) and offspring (decreased postnatal survival and pup body weight) toxicity was reported in a two-generation reproductive toxicity study in rats. A search of the toxicological literature found no additional data on the toxicity of trinexapac-ethyl. The U.S. EPA Office of Pesticide Programs developed an acute reference dose (arfd) for trinexapac-ethyl of 0.6 milligrams per kilogram body weight per day (mg/kg/day) for females age 13 to 49 years based on a no observed effect level (NOEL) of 60 mg/kg/day in a developmental toxicity study in rabbits (effects at higher doses were: decreased number of fetuses per litter and increased post-implantation loss) and an uncertainty factor of 100. An arfd was not developed for the general population (including infants and children) because there were no appropriate acute endpoints. Additionally, the U.S. EPA established a chronic reference dose (crfd) of 0.32 mg/kg/day based on a NOEL of 32 mg/kg/day from a chronic feeding study in dogs (effects at higher doses were: elevated serum cholesterol levels, mucoid feces, bloody feces, minimal focal vacuolation of the dorsal medial hippocampus and/or lateral midbrain) and an uncertainty factor of 100. The U.S. EPA established tolerances for trinexapac-ethyl in or on a number of agricultural crops and animal commodities (40 CFR ). The U.S. EPA also developed an acute population adjusted dose (apad) and a chronic population adjusted dose (cpad) for evaluating dietary exposures to trinexapac-ethyl from its use on food crops. The apad for females age 13 to 49 years is 0.6 mg/kg and has the same basis as the arfd. The cpad for the general population and all population subgroups is 0.32 mg/kg/day and has the same basis as the crfd. The U.S. EPA estimated that the acute dietary exposure to trinexapac-ethyl from all crops for which there are tolerances, and drinking water, would be 2 percent of the apad for females age 13 to 49 years. The estimated chronic dietary exposure to this active ingredient would be 2.5 percent of the cpad for the general population and 6 percent for children 1 to 2 years, the highest exposed subgroup. These exposure analyses are based on the assumption that 100

3 Ms. Susan Person 3. percent of crops are treated and contain tolerance level residues. Actual residues and resulting exposure levels are expected to be less than these assessments estimate. The U.S. EPA reported the results of an occupational risk assessment for inhalation and dermal exposure to trinexapac-ethyl from the labeled use of different product formulations of Palisade 2EC (liquid, wettable powder in water soluble bag and granule) for a variety of application methods (aerial, groundboom, chemigation, backpack sprayer, low pressure handwand, handgun sprayer, tractor drawn spreader, belly grinder and push type spreader) to several commodities (grasses grown for seed, sod, sugarcane, cereals, turf or golf course). For determining margins of exposure (MOEs), the U.S. EPA compared estimated short- (1-30 days)/intermediate-term (1-6 months) combined inhalation and dermal exposures to a NOEL of 60 mg/kg/day from a developmental toxicity study in rabbits (decreased number of fetuses per litter and increased post-implantation loss). The MOEs for short-/intermediate-term combined dermal and inhalation exposures for commercial mixers/loaders, applicators and mixers/loaders/applicators ranged from 600 to 18,000, 700 to 78,000, and 6,000 to 3,600,000, respectively, depending on the application method, commodity and product formulation. The MOEs for inhalation exposures to flaggers supporting aerial applications were estimated to range from 59,000 to 270,000 depending on the commodity and product formulation. These estimates assumed that workers wore a long-sleeved shirt and long pants, chemical-resistant gloves, shoes plus socks and protective eyewear as per label requirements. The estimated post-application short-/intermediate-term dermal exposures were compared to the NOEL from the developmental toxicity study in rabbits to determine MOEs. The MOEs for various post-application activities (maintenance, roll/slab/mechanical/hand harvesting, transplanting/planting, mechanical/hand weeding, fertilizing, irrigation and scouting) on the day of application ranged from 110 to 12,000. However, an MOE of 47 was calculated for hand harvesting sugarcane (which is not grown in New York State). The U.S. EPA estimated that an acceptable MOE of 100 would not be reached until 8 days after the application; however, label changes (increased Restricted Entry Interval or lower application rate) were not required because sugarcane is almost exclusively harvested mechanically in the U.S. and the label already requires a 28-day pre-harvest interval for sugarcane. A post-application risk assessment for inhalation exposures was not performed because of the low acute inhalation toxicity of trinexapac-ethyl and the formulated end product. The U.S. EPA considered MOEs of 100-fold or greater to provide adequate worker protection for these scenarios. There are no chemical-specific Federal or New York State drinking water/groundwater standards for trinexapac-ethyl. Based on its chemical structure, trinexapac-ethyl falls under the 50 microgram per liter (µg/l) general New York State drinking water standard for an unspecified organic contaminant (10 NYCRR Part 5, Public Water Systems). The available information on trinexapac-ethyl and Palisade 2EC indicates that they are not very acutely toxic via oral, dermal and inhalation routes of exposure. The formulated end product is moderately irritating to the skin and eyes and is a skin sensitizer. These risks should be mitigated through the use of the labeled personal protection equipment (long-sleeved shirt, long pants, chemical-resistant gloves, shoes and socks, protective eyewear) and other engineering controls (e.g., enclosed cockpit or tractor cab). Trinexapac-ethyl caused some toxicity in chronic oral, reproductive and developmental toxicity studies in laboratory animals,

4 Ms. Susan Person 4. but is considered not likely to be carcinogenic to humans. Although data from toxicity studies on trinexapac-ethyl indicate that this chemical has the potential to cause some adverse effects, the estimated exposure from the labeled use of this pesticide product should not pose significant health risks to workers or the general public. Given the above, the DOH does not object to the registration of Palisade 2EC in New York State on the basis of direct health risks from worker use or dietary exposures. ECOLOGICAL EFFECTS ASSESSMENT: The Department s Bureau of Habitat (BOH) evaluated the proposed use of trinexapacethyl as contained in Palisade 2EC. Shown below is the assessment. Toxicity: For most species tested, trinexapac-ethyl was classified by the U.S. EPA as ranging from practically non-toxic to slightly toxic. For mysid shrimp, representing marine/estuarine invertebrates, the U.S. EPA classified trinexapac-ethyl as moderately toxic. Chronic toxicity to freshwater fish was more significant, with both the no observed effects concentration (NOEC) and lowest effects concentration (LOEC) from a 35 day early life stage (ELS) test being below 1.0 mg/l. Freshwater invertebrates, represented by Daphnia magna, were less sensitive, with the NOEC and LOEC from a 21 day life cycle test being 5.1 mg/l 2.4 mg/l, respectively. The ecotoxicity data for trinexapac-ethyl are summarized in Table 1. Table 1. Summary of the ecotoxicological testing conducted with trinexapac-ethyl. Organism Test Result Comment Mammalian Rat Acute oral LD 50 > 4212 mg/kg Rat 90 day Subchronic LOEC: 5000 ppm Rat oral feeding study 2 generation chronic / reproduction feeding study NOEC: 500 ppm NOEL: 594 mg/kg bw Avian Mallard duck Acute oral > 2000 mg/kg bw Mallard duck Avian reproduction LOEC: >600 ppm NOEC: 600 ppm Bobwhite quail LOEC: 600 ppm NOEC: 200 ppm Aquatic freshwater fish Rainbow trout (Oncorhynchus mykiss) Bluegill (Lepomis macrochirus) Acute, 96 hour Acute 96 hour LC 50 : 68 mg/l NOEC: 30 mg/l LC 50 : >130 mg/l NOEC: 46.6 mg/l

5 Ms. Susan Person 5. Organism Test Result Comment Common carp Acute 96 hour LC 50 : 57 mg/l Supplemental (Cyprinus carpio) NOEC: 32 mg/l Channel catfish (Ictalurus punctatus) Acute 96 hour LC 50 : 35 mg/l NOEC: 20 mg/l Fathead minnow ELS 35 day Early Life Stage (ELS) First study LOEC: 0.89 mg/l NOEC: 0.14 mg/l Second study LOEC: 0.80 mg/l NOEC: 0.41 mg/l Aquatic freshwater invertebrates Daphnia magna 48 EC 50 immobilization EC 50 : >142.5 mg/l NOEC: 29 mg/l Daphnia magna 21 day life cycle First study (supplemental) LOEC: 21 mg/l NOEC: 11 mg/l Sheepshead minnow (Cyprinodon variegatus) Mysid shrimp (Americamysis bahia) Oyster larvae (Crassostrea virginica) Marine/Estuarine 96 hour acute LC 50 : 180 mg/l NOEC: < 60 mg/l 96 hour acute LC 50 : 6.5 mg/l NOEC: <3.4 mg/l 96 hour EC 50 for EC 50 : 89 mg/l shell deposition NOEC: <8.4 mg/l Second study (Core) LOEC: 5.1 mg/l NOEC: 2.4 mg/l Aquatic macrophyte Lemna gibba Green algae Selenastrum capricornutum Blue-green algae Anabaena flos-aquae FW diatom Navicula pelliculosa Marine diatom Skeletonema costatum 14 day static EC 50, frond count 120 hour EC 50, cell density 120 hour EC 50, cell density 120 hour EC 50, cell density & growth rate 120 hour EC 50, cell density EC 50 : 0.19 mg/l NOEC: mg/l EC 50 : 9.4 mg/l NOEC: 3.0 mg/l EC 50 : 0.35 NOEC: 0.11 mg/l EC 50 : 42 mg/l NOEC: 13 mg/l EC 50 : 16 mg/l NOEC: 3.7 mg/l Terrestrial invertebrates Honeybee Acute contact LD 50 : 47 μg/bee NOEC: 13 μg/bee Supplemental

6 Ms. Susan Person 6. Exposure: A. Summary of Environmental Fate In soil, the primary route of degradation is microbial metabolism. The degradation of trinexapac-ethyl and its major metabolite (CGA ) from aerobic microbial metabolism was very rapid, with half-lives (T 1/2 ) ranging from 0.03 to 5.3 days in different types of soil (see Table 2). Under anaerobic conditions, trinexapac-ethyl was degraded by microbial metabolism much more slowly, with T 1/2 ranging from days. In moist, non-sterile soil, trinexapacethyl was degraded by photolysis quickly, with T 1/2 of hours, but in dry sterile soil, the photolysis T 1/2 79 days, suggesting that the photolytic degradation rate in non-sterile soil was microbially mediated. Table 2. Degradation of trinexapac-ethyl and metabolite in aerobic soil from microbial metabolism. Soil type Trinexapac-ethyl parent CGA metabolite DT 50 * - days DT 90 ** - days DT 50 * - days DT 90 ** - days Loam Sandy loam Loamy sand * DT 50 Time in days for 50% of the applied material to dissipate ** DT 90 Time in days for 90% of the applied material to dissipate Four field dissipation studies were conducted, in California, New York, North Carolina, and Illinois. In all studies, trinexapac-ethyl dissipated very rapidly. The CGA metabolite persisted longer but still dissipated reasonably quickly, see Table 3. When the geometric mean is determined for all applications in all locations on all different types of surfaces, the mean field dissipation halflife for trinexapac-ethyl is 1.09 days and 12 days for the CGA metabolite. Table 3. Field dissipation of trinexapac-ethyl and its major metabolite State Treatment applied to: Half-life (T 1/2 ) in days Trinexapac-ethyl CGA Grass, 1 st application Grass, 2 nd application CA Thatch /sod, 1 st app Thatch/ sod, 2 nd app 1.1 NR* Bare ground Grass, 1 st application Grass, 2 nd application NR NY Thatch /sod, 1 st app Thatch/ sod, 2 nd app NR Bare ground NC Grass, 1 st application Grass, 2 nd application NR NR Thatch /sod, 1 st app Below limit of 2.89

7 Ms. Susan Person 7. IL Thatch/ sod, 2 nd app detection (LOD), days after treatment (DAT) Bare ground 1.4 NR Grass, 1 st application Grass, 2 nd application Thatch /sod, 1 st app Thatch/ sod, 2 nd app NR 27 Bare ground Geometric mean of all halflives in days * NR Not Reported In water, trinexapac-ethyl was degraded by hydrolysis only at very basic ph. At ph of 9, it degraded with a half- life of 8.1 days. At ph of 5 or 7, the half-life from hydrolysis was > 30 days. It degraded more rapidly in water by aqueous photolysis. In two aqueous photolysis studies, halflives of 5.3 and 21.3 days were reported, with a geometric mean of 10.6 days for both studies. The half-life for aerobic aquatic metabolism was days for the parent molecule, and days for the parent plus metabolites. Under anaerobic conditions, the half-life was 3.5 days for the parent, and days for the parent plus metabolites. B. Major degradates and degradation pathways The primary degradate of trinexapac ethyl is the free acid form (CGA179500). In studies of the photolytic degradation of trinexapac-ethyl, up to 56% was transformed to CGA Other degradates include CGA , an open chain cyclohexane ring and another unidentified product. No toxicity data were provided for any of the degradates. CGA is more persistent than the parent trinexapac-ethyl molecule, and its degradation is evaluated in field dissipation studies. C. Exposure assessment modeling The MAMTOX and AVTOX models showed that no acute or chronic toxicity thresholds for birds or mammals were exceeded when trinexapac-ethyl was applied at the maximum application rate. For aquatic runoff, the PONDTOX model was run using the maximum application rate of 0.5 lbs AI/acre. Using the 5% runoff rate, the NOEC for aquatic macrophytes was exceeded in the 1 foot and 3 foot ponds. When the 3% runoff rate was used, the NOEC for aquatic macrophytes was marginally exceeded only in the 1 foot pond. Trinexapac is applied to foliage. When an estimated 50% of the applied active was removed due to foliar intercept and the model run with the 3% runoff rate, no risk thresholds were exceeded.

8 Ms. Susan Person 8. Risk Assessment: Trinexapac-ethyl exhibits low toxicity to most fish and wildlife species tested. It has some potential for chronic toxicity to fish. However, when exposure is considered, the potential for risk is diminished significantly. Trinexapac-ethyl degrades very rapidly when applied, greatly reducing the likelihood that it would be transported to water by runoff. Summary and Conclusion: Because of the rapid degradation of trinexapac-ethyl on turf and soil and its generally low toxicity, this material is unlikely to pose any significant risk to fish and wildlife when used as labeled. Therefore, the Bureau of Habitat does not object to the registration of a major change in labeling for trinexapac-ethyl. ENVIRONMENTAL FATE ASSESSMENT: The following technical review was produced by the Department s Engineering Geology staff within the Bureau of Pest Management: DERs were not submitted therefore this review was prepared from the "EFED Environmental Risk Assessment of Proposed Label for Palisade EC and Palisade 2 EC (Trinexapac-ethyl), New Uses on Cereals, Sugarcane and Grasses Grown for Seed Revised dated December 13, TRANFORMATION PRODUCTS: CGA (trinexapac-acid) CGA Open chain cyclohexane ring Solubility: The solubility at ph 5.5 is 10,200 mg/l, and 21,100 at ph 8.2 at 25 o C. Hydrolysis: Trinexapac-ethyl is stable to hydrolysis in acidic and neutral conditions and hydrolyzes under basic conditions (t½ = 8.1 days). The neutral phs of the environmental compartments in the soil and aquatic metabolism studies suggest microbial-mediated hydrolysis. Aqueous and Soil Photolysis: Photodegradation does not appear to be a major degradation pathway. The aqueous study shows an environmental phototransformation half-life of about 18 days. In the soil study, the compound was considered stable since the extrapolated half-life was well beyond the duration of the study. Aerobic Soil and Aerobic/Anaerobic Aquatic Metabolism: Biodegradation appears to be the major dissipation pathway for trinexapac-ethyl. In an aerobic metabolism study, half-lives ranged from 2.8 hours in a loam soil to 4.3 days in a loamy sand soil. In an aerobic aquatic metabolism study, half-lives ranged from 2.8 days in a river water-sand sediment system to 4.0 days in a pond water/sandy clay loam sediment system. In an anaerobic aquatic metabolism study, half-lives averaged 3.5 days in a pond water/lake water-sediment system. Biodegradation was slower under anaerobic soil conditions. The estimated half-life is about 25 days in a sandy loam soil.

9 Ms. Susan Person 9. Aerobic Soil Metabolism for Parent and Degradates: The U.S. EPA used the Total Toxic Residues method (TTR) for environmental modeling. This method determines the half-life of the parent and three degradates (CGA (trinexapac-acid), CGA , and the open chain cyclohexane ring) together. The EPA calculates the half-life for each molecule and then adds them together. The cumulative half-life for all three together was 3.0 to 5.2 days. Adsorption/Desorption: According to the study summary for MRID for the parent: Soil ph %OM Adsorption K oc Desorption K oc Clay Sand Sandy loam Loam Adsorption/Desorption for Degradate CGA : According to the study summary for MRID for the degradate: Soil ph %OM Adsorption K oc Desorption K oc Clay Sand Sandy loam Loam Terrestrial Field Dissipation: Under typical use, the vast majority of the trinexapac-ethyl and its major metabolite, trinexapac acid, dissipated in the grass and thatch and sod layer by study termination. Following the final application, dissipation half-lives were less than 3 days for trinexapac-ethyl and ranged from 5.1 to 36.5 days for trinexapac acid. Computer Modeling: Staff modeled this active ingredient using the TTR half-life value. This U.S. EPA method determines the cumulative half-life of the parent and the three degradates, which in this case is 5.2 days. The parent half-life is hours, and the three degradates make up the rest of the half-life. Running LEACHP on Riverhead soil using a K oc of 60, the TTR half-life of 5.2 days, and an application rate of 0.5 lbs ai/a/yr (100 percent of applied), the model predicted two peaks, one reaching about 0.05 ppb, and one reaching 0.02 ppb. Summary: The EPA completed a review of this active ingredient for new uses in 2011 using the TTR approach for the parent and degradates. The TTR half-life for the parent and degradates added together was only 5.2 days, and running the modeling at the lowest K oc (the most conservative approach possible), the model projects leaching at or less than 0.05 ppb. Therefore, Engineering Geology staff does not object to the registration of this product as labeled.

10 Ms. Susan Person 10. REGISTRATION DECISION: The Department concludes that the proposed use of Palisade 2EC on wheat, barley, sugarcane, and grasses grown for seed should not have an adverse effect on human health, the fish and wildlife resources, or the water resources of New York State when used as labeled. Therefore, the Department approves your application for a major change in labeling for the active ingredient trinexapac-ethyl. Palisade 2EC has been registered as a general use product in New York State. Enclosed for your record are copies of the Certificate of Pesticide Registration and stamped Accepted for Registration label. Please note that a proposal by Syngenta Crop Protection, Inc. or any other registrant to register a product that contains trinexapac-ethyl, and whose labeled uses are likely to increase the potential for significant impact on humans, nontarget organisms, or the environment, would constitute a major change in labeling. Such an application must be accompanied by a new application fee and meet the requirements listed in Appendix 1.B. of New York State Pesticide Product Registration Procedures (April 2009). Such information, as well as forms, can be accessed at our website as listed in our letterhead. letter. Please contact Shaun Peterson, at , if you have any questions regarding this Sincerely, Scott Menrath Scott Menrath, P.E. Director Bureau of Pest Management Enclosures