Please see the full assessments from the New York State Department of Health and this Department in the Appendix to this letter.

Transcription

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 January 10, 2014 VIA UPS (100) Ms. Susan Person Syngenta Crop Protection, LLC 410 South Swing Road, Greensboro, North Carolina Dear Ms. Person: Re: Application for Registration of the New Active Ingredient Sedaxane as Contained in Vibrance (EPA Reg. No ), Vibrance Extreme (EPA Reg. No ) and CruiserMaxx Vibrance Cereals (EPA Reg. No ) (Chemical Code ) The New York State Department of Environmental Conservation (Department) has reviewed the new application, received April 19, 2013, and the additional information, received June 28, 2013, from Syngenta Crop Protection, to register the new active ingredient sedaxane as contained in the abovereferenced pesticide products. Sedaxane is a fungicide proposed as a commercial seed treatment for cereal grains such as barley, wheat, oat, rye and corn, as well as soybean, canola, and dried shelled peas and beans. In addition to the new active ingredient, Vibrance Extreme contains difenoconazole and mefenoxam, and CruiserMaxx Vibrance Cereals contains difenoconazole, mefenoxam and thiamethoxam. Difenoconazole, mefenoxam and thiamethoxam are currently registered as seed treatments in New York State. The application package was deemed complete for purposes of technical review on August 15, Pursuant to the review time frame specified in Environmental Conservation Law (ECL) , a registration decision date of January 10, 2014 has been established. Vibrance (EPA Reg. No ) contains 4.3 lbs. of sedaxane per gallon and was initially proposed for barley, canola, oat, rye, soybean, triticale, and wheat. A revised label was received August 13, 2013 adding dried shelled peas and beans, chickpeas, lentils, fava beans, sorghum, the rapeseed subgroup (including canola), and corn. Vibrance Extreme (EPA Reg. No ) contains lbs. of sedaxane per gallon, as well as lbs. of difenoconazole and lbs. of mefenoxam per gallon and is labeled for barley, oats, rye, triticale and wheat. CruiserMaxx Vibrance Cereals (EPA Reg. No ) contains lbs. of sedaxane, lbs. of difenoconazole, lbs. of mefenoxam, and lbs. of thiamethoxam per gallon and is labeled for use on barley, oats, rye, wheat and triticale. The application rate for all the labeled crops is 0.04 to 0.09 ounces sedaxane per 100 lbs. of seed, except for the control of head smut in corn on the Vibrance label which has an application rate of 0.32 to 0.64 ounces sedaxane per 100 lbs. of seed. All three product labels allow for two treated seed plantings per season.

2 Ms. Susan Person 2. The Department and the New York State Department of Health evaluated the application and all supporting documents submitted to date regarding human health, fish and wildlife resources, and ground and surface water resources of New York State. After careful consideration of all information, the Department has concluded that the use of the sedaxane products should not have an adverse effect on the health of applicators or the general public, the fish and wildlife resources, or the ground and surface water of New York State when used as labeled. Please see the full assessments from the New York State Department of Health and this Department in the Appendix to this letter. The Department hereby accepts the new active ingredient, sedaxane, as contained in Vibrance (EPA Reg. No ), Vibrance Extreme (EPA Reg. No ) and CruiserMaxx Vibrance Cereals (EPA Reg. No ) for registration as labeled in New York State. Enclosed for your files are the Certificate of Pesticide Registration and New York State stamped Accepted labeling for the three products. Please note, a proposal Syngenta Crop Protection, or any registrant to register a product containing sedaxane whose labeled uses are likely to increase the potential for significant exposure to humans, nontarget organisms, or the environment, would constitute a major change in labeled use pattern. Such an application must be accompanied by a new application fee and meet the requirements specified in 6NYCRR Part Please contact, Jeanine Broughel, Chief of the Product Registration and Pest Management Alternatives Section, at (518) , if you have any questions. Enclosures Sincerely, Scott Menrath Scott Menrath, P.E. Director Bureau of Pest Management.

3 Ms. Susan Person 3. HUMAN HEALTH RISK ASSESSMENT APPENDIX The New York State Department of Health (NYSDOH) reviewed the data submitted by Syngenta Crop Protection in support of the registration of new active ingredient sedaxane. The NYSDOH stated that neither sedaxane nor the formulated products Vibrance, Vibrance Extreme and CruiserMaxx Vibrance Cereals were very toxic in acute oral, dermal or inhalation exposure studies in laboratory animals. In addition, neither the active ingredient nor the formulated products were irritating to the eyes and skin (tested on rabbits) or dermal sensitizers (tested on guinea pigs). Both acute and subchronic oral neurotoxicity studies were conducted on sedaxane in rats. In the acute study, neurotoxic effects including reduced activity, decreased rearing, initial inactivity, piloerection, ruffled fur and recumbency in males and decreased activity, locomotor activity and rearing in females at a dose level of 250 mg/kg; the NOEL was 30 mg/kg. Systemic toxicity consisted of decreased body weight, body weight gains and food consumption in males plus weakened condition, swaying gait, and reduced muscle tone in females at 250 mg/kg; the NOEL was 30 mg/kg. In the subchronic study, dietary administration of sedaxane caused reduced motor activity as well as decreased body weight, body weight gains, food consumption and food efficiency at 260 mg/kg/day in males and 303 mg/kg/day in females; the respective NOELs were 66 mg/kg/day and 79.7 mg/kg/day. The U.S. EPA Office of Pesticide Programs calculated an acute oral reference dose (arfd) of 0.3 mg/kg/day for sedaxane based on the NOEL of 30 mg/kg/day from the acute neurotoxicity study in rats and an uncertainty factor of 100. Sedaxane caused some toxicity in chronic animal feeding studies. In a oneyear dog feeding study, sedaxane caused decreased body weights, body weight gains and food consumption, decreased spleen weights in both sexes, plus decreased glucose levels and decreased testes weight in males at a dose of 200 milligrams per kilogram body weight per day (mg/kg/day); the noobservedeffect level (NOEL) was 50 mg/kg/day. In a chronic feeding/oncogenicity study in mice, decreased body weight, body weight gains, and food efficiency were reported at doses of 900 mg/kg/day for males and 1,001 mg/kg/day for females; the NOELs were 157 mg/kg/day for males and 185 mg/kg/day for females. In a chronic feeding/oncogenicity study in rats, increased liver weight, increased incidences of hepatocyte hypertrophy and eosinophilic foci, plus increased phosphate levels in males; decreased body weight and body weight gain and increased liver weight in females; as well as thyroid follicular cell hypertrophy in both sexes were reported at doses of 67 mg/kg/day for males and 86 mg/kg/day for females; the respective NOELs were 11 mg/kg/day and 14 mg/kg/day. The U.S. Environmental Protection Agency (U.S. EPA) Office of Pesticide Programs calculated a chronic oral reference dose (crfd) of 0.11 mg/kg/day for sedaxane based on the NOEL of 11 mg/kg/day in male rats and an uncertainty factor of 100. This RfD has not yet been adopted by the U.S. EPA s Integrated Risk Information System (IRIS). A current search of the toxicological literature did not find any significant new information on the toxicity of sedaxane. Sedaxane caused some developmental toxicity in the offspring of pregnant rats and rabbits exposed to this chemical during organogenesis at doses that also caused maternal toxicity. In the rat study, decreased fetal weights were reported in offspring at a dose of 200 mg/kg/day; the NOEL was 100 mg/kg/day. Maternal toxicity consisted of decreased body weight, body

4 Ms. Susan Person 4. weight gain and food consumption at a dose of 200 mg/kg/day; the NOEL was 100 mg/kg/day. In the rabbit study, sedaxane caused an increase in abortions, unossified sternebrae and 13th rudimentary ribs as well as a decrease in fetal weights at 200 mg/kg/day; the NOEL was 100 mg/kg/day. Maternal toxicity consisted of increased abortions, decreased body weight gain, food consumption and defecation at a dose of 200 mg/kg/day; the NOEL was 100 mg/kg/day. In a multigeneration reproduction study in rats, sedaxane was associated with decreased body weight and increased liver weights in offspring at a dose of 150 mg/kg/day; the NOEL was 50 mg/kg/day. Parental toxicity consisted of decreased body weight, body weight gain and food consumption as well as increased liver weights and abnormally darkened livers in females at 150 mg/kg/day; the NOEL was 50 mg/kg/day. Sedaxane caused tumors at multiple sites in mice and rats in chronic feeding studies. In mice, there was a treatmentrelated increase in the incidence of liver adenomas, carcinomas and combined adenomas and/or carcinomas in males at the highest dose group when compared to controls. In a chronic feeding study in rats, sedaxane caused treatmentrelated increases in thyroid follicular cell adenomas and liver adenomas in males. Sedaxane additionally caused statistically significant increases in combined adenoma and/or adenocarcinoma uterine tumors at all dose levels in female rats. Sedaxane was negative in a number of genotoxicity studies. Based on these data, the U.S. EPA classified sedaxane as likely to be carcinogenic to humans. To evaluate cancer risks, the U.S. EPA derived a cancer potency factor (CPF) of 4.64 x 10 3 (mg/kg/day) 1, based on the increased incidence of benign and malignant uterine tumors combined in female rats. The U.S. EPA established tolerances of sedaxane for commodities of barley, canola, oat, rye, soybean and wheat (Federal Register 77: 36,919 24, June 20, 2012). The acute population adjusted dose (apad) for the general U.S. population and all population subgroups for sedaxane is 0.3 mg/kg/day and has the same basis as the arfd. The chronic population adjusted dose (cpad) for propiconazole is 0.11 mg/kg/day and has the same basis as the crfd. The U.S. EPA estimated that acute and chronic dietary exposures to sedaxane residues from all crops for which there are tolerances and from drinking water would be less than 1 percent of the apad (acute exposures) and cpad (chronic exposures) for the general U.S. population and all population subgroups. Additionally, the cancer risk for the general U.S. population from exposure to sedaxane from drinking water and all registered crop uses was estimated to be 7 x These exposure analyses are based on the assumption that 100 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 additionally reported the results of a cancer and noncancer occupational risk assessment for short and intermediateterm inhalation exposures to sedaxane for primary handlers (treating seed) in commercial and onfarm treatment scenarios and secondary handlers (planting treated seed). Dermal risks were not addressed because a dermal toxicity endpoint was not identified for sedaxane. For determining margins of exposure (MOEs), the U.S. EPA compared estimated short (1 30 days) and intermediateterm (1 6 months) inhalation exposures to a NOEL of 30 mg/kg/day from an acute neurotoxicity study in rats (reduced activity, decreased rearing, initial inactivity, piloerection, ruffled fur and recumbency in males and decreased activity, locomotor activity and rearing in females). The MOEs for the primary handling tasks of loader/applicator, sewer, bagger and other activities to support seed treatment were 1.7 x 10 5, 2.5 x 10 5, 3.7 x 10 5 and 3.7 x 10 4, respectively. For primary handlers of onfarm treatment, the short/intermediateterm inhalation MOEs ranged from 1.2 x 10 6 to 5.5 x 10 7,

5 Ms. Susan Person 5. depending on the commodity being treated. The MOEs for secondary handlers ranged from 4.1 x 10 5 to 1.9 x 10 6, depending on the commodity being planted. The estimated lifetime cancer risk for primary handlers, using the CPF of 4.64 x 10 3 (mg/kg/day) 1 and assuming workers are exposed to sedaxane for 30 days per year over a 70year lifetime, was estimated to range between 5.64 x 10 7 and 1.28 x 10 6 for commercial seed treatment and 5.81 x 10 8 to 2.73 x 10 6 for onfarm seed treatment. In addition, the estimated lifetime cancer risk for secondary handlers planting treated seeds ranged between 2.53 x 10 7 and 1.69 x These estimates assumed that workers wore longsleeved shirt and long pants, shoes plus socks and chemicalresistant gloves as per label requirements. Generally, the U.S. EPA considers MOEs of 100fold or greater and cancer risks below 1 x 10 4 to provide adequate worker protection. There are no chemical specific federal or New York State drinking water/groundwater standards for sedaxane. Based on its chemical structure, this chemical falls under the 50 microgram per liter (µg/l) New York State drinking water standard for unspecified organic contaminants (10 NYCRR Part 5, Public Water Systems). The testing results indicate that sedaxane meets the definition of an oncogen in 6 NYCRR Part If one uses the U.S. EPA derived CPF 4.64 x 10 3 (mg/kg/day) 1 and procedures for deriving ambient water quality standards and guidelines based on oncogenic effects (6 NYCRR Part 702.4), the value that is associated with a oneinamillion increased lifetime cancer risk is 7.5 µg/l. This value could be used to derive a screening value for comparison to estimated impacts to groundwater and surface water. In addition, the U.S. EPA has established chronic, noncancer and cancer Human Health Benchmark doses (i.e., level in drinking water at or below which adverse health effects are not anticipated from lifetime exposure) for sedaxane of 770 µg/l and 8 x 10 6 µg/l, respectively. These guideline values have been developed for pesticide active ingredients that may be found in surface or ground water sources of drinking water to enable stakeholders to better determine whether the detection of a pesticide in drinking water or source waters for drinking water may indicate a potential health risk. Neither sedaxane nor the formulated products were very acutely toxic or irritating in laboratory animal studies. Sedaxane caused some effects in neurotoxicity, chronic, developmental, and reproductive toxicity animal feeding studies. This chemical caused significant tumor increases in two rodent carcinogenicity studies and the U.S. EPA classified sedaxane as likely to be carcinogenic to humans. Generally, the NYSDOH has concerns about registering a pesticide product for use on food crops when it has oncogenic properties. However, sedaxane is not labeled for direct application to crops and exposure to the general public would be minimal given the labeled use of the formulated products as a seed treatment. Also, estimated dietary risks from exposure to sedaxane via crop residues and drinking water are very low and were considered acceptable by the U.S. EPA. In addition, estimated risks posed by sedaxane to workers from use of this product are within the range considered acceptable by the U.S. EPA. Therefore, there were no objections to the registration of Vibrance, Vibrance Extreme and CruiserMaxx Vibrance Cereals in New York State. ENVIRONMENTAL FATE AND GROUNDWATER IMPACTS: The Department s groundwater staff reviewed the information submitted in support of the registration of the new active ingredient sedaxane. The following is the groundwater staff s review:

6 Ms. Susan Person 6. Major Transformation Products The following is a list of the major (>10%) degradation products across all submitted environmental fate studies. The two degradates in bold undergo LEACHP modeled due to their being produced in the aerobic soil metabolism study. The bold Maximum Percent of Applied values listed in the table have been used to determine their maximum seasonal application rates relative to the parent sedaxane: CSCD Difluoromethyl1Hpyrazole4carboxylic acid 3Difluoromethyl1methyl1Hpyrazole4arboxylic acid CSCD Difluoromethyl1methyl1Hpyrazole4carboxylic acid [2(3 cyclopropyl1,3dihydroxypropyl)phenyl]amide CSCD {2[(3Difluoromethyl1methyl1Hpyrazole4carbonyl)amino] phenyl}3hydroxypropionic acid Degradate Study MRID Max. Percent of Applied CSCD Aerobic Soil Metabolism Aerobic Soil Metabolism Aqueous Photolysis CSCD Aqueous Photolysis CSCD Aqueous Photolysis Water Solubility MRID The following table lists the water solubilities of sedaxane and the two major degradates produced in the aerobic soil metabolism study. In the U.S. EPA memo it was noted on page 34 under Water Solubility that no solubility data were provided for any of the transformation products but they are expected to be more soluble than the parent sedaxane. Regarding the solubility of the degradate CSCD465008, on page 31 it is noted that, Based on EpiWeb 4, the degradate is several orders of magnitude more soluble than the parent. The 100 mg/l values listed in the table were taken from the University of Hertfordshire s (U.K.) Pesticide Properties Database and have been used for LEACHP modeling purposes. Compound Temperature Water Solubility ( C) (mg/l) Sedaxane CSCD Aqueous Hydrolysis MRID In an acceptable study at 20 C and 50 C, sedaxane was found to be stable to hydrolysis at ph 4, 7, and 9. Aqueous Photolysis MRID In a supplemental study at 25 C, the environmental phototransformation halflife of sedaxane was found to be 46 days. The major degradate was found at 25.96% of the initially applied parent. This value (25.96%) has been used for LEACHP modeling.

7 Ms. Susan Person 7. Soil Photolysis MRIDs and In two supplemental studies at 20 C, the maximum halflives of sedaxane ranged from 213 days to 292 days with a mean halflife at 253 days. No major degradates were produced. Since sedaxane is a seed treatment product, it is not expected to undergo significant photodegradation since the seeds are planted underground. Aerobic Soil Metabolism MRIDs , , and In three supplemental studies it was shown that sedaxane is not as persistent in the soil when it is applied to seed as when it is applied directly to soil. The major degradate formed in these studies were and CSCD with a respective maximums across all studies at 14% and 32% of the initially applied sedaxane rate of lbs a.i./acre/growing season. Because the percent organic carbon (%OC) value for the California sand is below 1%, such as it is in Riverhead soils, the halflife for the California sand (78 days for seed treatment and 373 days for soil treatment) has been used for LEACHP modeling (bold type in table) of sedaxane. This is supported by the notation on page 28 of the U.S. EPA memo that reads, The leaching potential of sedaxane through soil is correlated with the organic carbon fraction of the soil. The soil ph and %OC values for the soils used in MRIDs and were not provided in the submitted materials. Aerobic Soil Metabolism Sedaxane Extracted Parent from Seed or Soil Studies MRID Soil Type ph %OC HalfLife (Days) (seed) Major Degradate(s) % of Initial Applied Gatrenacker loam 71 CSCD Marsillargues silty clay (seed) (seed) (soil) Gartenacker loam 54 Paperlacker loamy sand Aces sandy clay 95 Gartenacker loam California sand North Dakota sandy clay loam Gartenacker loam California sand North Dakota clay loam CSCD CSCD CSCD CSCD CSCD CSCD

8 Ms. Susan Person 8. Aerobic Soil Metabolism of Degradate CSCD MRIDs , Two supplemental aerobic soil metabolism studies were conducted using the degradate CSCD and the halflives are listed in the following table. There is some inconsistency regarding the halflife values found in the MRID study and those listed in the EPA memo for that study. The MRID document listed the halflives for Marsillargues, Gartenacker, and 18 Aces at 190, 129, and 78 days, respectively, while the EPA memo had them at 324, 266, and 168 days. For LEACHP modeling, this reviewer takes a more conservative position and uses the values that appear in the U.S. EPA memo (bold value below). The soil ph and %OC values for the soils used in MRIDs and were not provided. Aerobic Soil Metabolism of Degradate CSCD Extracted from Seed or Soil Studies MRID Soil Type ph %OC HalfLife (Days) (seed) (soil) Major Degradate(s) Marsillargues silty clay 324 Bound Residues CO 2 Gartenacker loam 266 Bound Residues CO 2 18 Aces sandy clay 168 Bound Residues CO 2 Marsillargues silty clay 157 Bound Residues CO 2 Gartenacker loam 99 Bound Residues CO 2 18 Aces sandy clay 40 Bound Residues CO 2 % of Initial Applied Although an aerobic soil metabolism study was not provided for degradate CSCD798670, the molecular structure is nearly identical to degradate CSCD465008, therefore, they should model similarly using the LEACHP model. Anaerobic Soil Metabolism MRID In a supplemental study it was shown that the anaerobic soil metabolism halflife at 20 C was 375 days. No major degradates were reported. Adsorption/ Desorption Sedaxane MRID In an acceptable study, it was found that sorption was slightly nonlinear with equilibrium concentration so the Freundlich KFOC values were reported and have been used in LEACHP modeling. The KFOC values ranged from to which, according to the McCall Classification scale indicates that sedaxane has low potential mobility in all tested soils, with the exception of Gartenacker where it has medium potential mobility in soil. It is noted on page 35 of the U.S. EPA memo that soil adsorption of sedaxane was shown to correlate with the organic carbon content. Because the Visalia soil (soil type unknown) has ph and %OC values most similar than the others to Riverhead soil (bolded values below), the corresponding KFOC value have been used in LEACHP modeling.

9 Ms. Susan Person 9. MRID Adsorption/Desorption Sedaxane Soil Type ph % OC Adsorption K FOC Gartenacker loam Marsillargues silty clay Acres sandy clay Visalia Washington Champaign Adsorption/ Desorption of Degradate CSCD MRID In an acceptable study, it was found that sorption was slightly nonlinear with concentration so the Freundlich KFOC values were reported and have been used in modeling. The KFOC values ranged from 0.55 to 3.59 which indicates that degradate CSCD is mobile in soil. In regards to modeling, the Marsillargues %OC is more similar to Riverhead soil so a LEACHP profiles have been generated using KFOC MRID Adsorption/Desorption Degradate CSCD Soil Type ph % OC Adsorption K FOC Marsillargues silty clay Gartenacker loam Acre sandy clay Although an adsorption/desorption study was not provided for degradate CSCD798670, the molecular structure is nearly identical to degradate CSCD so they should model similarly using the LEACHP model. Terrestrial Field Dissipation MRIDs , Two supplemental studies were and the sedaxane halflives are listed in the following table. Sedaxane was primarily confined to the top 4 inches indicating a low downward mobility potential. MRID Soil Type ph % OC North Dakota/ sandy loam Washington/ loamy sand California/ sandy loam Half Life (Days) Max. Detection Depth in in in Route of Dissipation Degradate(s) None None None

10 Ms. Susan Person 10. MRID Soil Type ph % OC France/ silt loam Italy/ silty clay loam Half Life (Days) Max. Detection Depth cm cm Route of Dissipation Degradate(s) None None LEACHP Modeling The following tables list the LEACHP modeling parameters that were used for the parent sedaxane and the two major degradates that were produced in the aerobic soil metabolism studies. Two LEACHP profiles were made for the parent sedaxane, one to reflect application to seed and the other to reflect direct application to soil. The application rates of the degradates are based on their maximum recoveries across all environmental fate studies and the maximum seasonal seed treatment rate for the parent sedaxane at 0.32 fl oz (two applications at 0.16 fl oz) per 100 lbs of seed per acre per growing season. Compound Application Rate 1 (lbs ai/acre/season) Water Solubility (mg/l) K OC (ml/g) Sedaxane 1.08E (K FOC ) HalfLife (Days) 78 (seed treatment) 373 (soil treatment) CSCD E E These application rates reflect: (1) the maximum percentage formed from parent across environmental fate studies and (2) the molecular weight ratios of degradate to parent. Conclusions LEACHP modeling shows that sedaxane when used as a seed treatment as labeled has a maximum leaching concentration at ppb and the two degradates CSCD and had maximum leaching concentrations at 0.13 and 0.11, respectively. As a result, staff do not object to the registration of the new active ingredient sedaxane when used as labeled. ECOLOGICAL RISK ASSESSMENT The Department s Division of Fish, Wildlife and Marine Resources Bureau of Habitat (BOH) reviewed the information submitted in support of the registration of the new active ingredient sedaxane. The following is the BOH s review: Use Profile Sedaxane is a new systemic fungicidal active ingredient included in three preplant seed treatment formulations. All three product labels include adequate language with regard to minimizing nontarget exposure. The application rates for the other three active ingredients in these products are well below those reviewed previously by BOH.

11 Ms. Susan Person 11. Vibrance fungicide is labeled for control of several smuts Ustilago sp., and Seed Decay, Seedling Blight, and Dampingoff caused by Rhizoctonia sp. in: barley, canola, corn *, oat, rye, soybean, triticale, and wheat. It contains 45.45% (4.3lb. per gallon) sedaxane as its sole active ingredient. It is applied as a waterbased slurry using standard seed treatment equipment at rates of fluid ounces of formulation per 100 pounds of seed. Vibrance Extreme is 1.22% sedaxane (0.115 lb./gal), 5.86% difenoconazole (0.552 lb./gal), and 1.46% mefenoxam (0.138 lb./gal). In addition to the disease agents controlled by Vibrance above, it is labeled for control of those caused by Fusarium sp., Pythium sp., Cochliobolus sp., Septoria sp., and Tilletia sp. et al. in: barley, oats, rye, triticale, and wheat. It is applied to seed in the same manner as Vibrance at rates of fl.oz. formulation / 100 lbs. seed. Difenoconazole and mefenoxam are also fungicides. CruiserMaxx Vibrance Cereals is 0.72% sedaxane ( lb./gal), 3.34% difenoconazole (0.308 lb./gal), 0.86% mefenoxam (0.079 lb./gal), and 2.78% thiamethoxam (0.256 lb./gal). It is applied to barley, oats, rye, triticale, and wheat seed in the same manner as the other products at 510 fl.oz./100 lbs. seed. Thiamethoxam is a systemic neonicotinoid insecticide added to protect against chewing or sucking insect pests. The application rates for the products are low and vary considerably with the seeding rate of the treated crops. The maximum per acre seeding rates for the labeled crops range from 5 lbs./acre for Canola to 167 lbs./acre for soybeans. Table 1 summarizes calculation of maximum peracre application rates for the active ingredients contained in each of the three formulations. Table 1. Application Rate Calculations Summary Product AI Amt of AI / 100 lbs. Seed (lbs) Max Seeding Rate of product (lbs./acre) (crop) AI / Acre at max seeding rate (lbs) Vibrance sedaxane (Soybean) sedaxane (Wheat) Vibrance Extreme difenoconazole mefenoxam CruiserMaxx Vibrance Cereals sedaxane (Wheat) difenoconazole mefenoxam thiamethoxam Chemical Description & Mode of Action Sedaxane, N[2[1,1 bicyclopropyl]2ylphenyl]3 (difluoromethyl)1methyl1hpyrazole4carboxamide, is a pyrazolecarboxamide within the anilide chemical class. It inhibits succinate dehydrogenase, an enzyme linked to the mitochondrial electron transport chain * The MCL registration application for use on corn was received while the sedaxane evaluation was under way. BOH agreed to roll it into the current review.

12 Ms. Susan Person 12. Sedaxane has a water solubility of 14 mg/l. Its octanol/water partitioning coefficient, K OW, is The mean soil organic carbon partitioning coefficient, K OC, is 537 ml/g indicating moderate post application mobility potential. Sedaxane vapor pressure is low, 4.9 X mm Hg, volatilization will not contribute significantly to its dissipation. Toxicity & Environmental Fate Sedaxane has low toxicity to terrestrial vertebrate test species but can be highly toxic to aquatic organisms. It is expected to be persistent postapplication. Sedaxane is practically nontoxic to birds or mammals on an acute basis. High doses over extended periods, however, can result in chronic toxicity in mammals with many organs being affected. Increased incidence of liver and thyroid adenomas were observed in rat oncogenicity studies. Increased incidence of hepatocellular adenomas, carcinomas, and combined adenoma/carcinomas were observed in mouse studies. Sedaxane is classified as a likely human carcinogen. Eight different mammalian genotoxicity/cytotoxicity studies were submitted, all results were negative. Aquatic animals are more sensitive to sedaxane than terrestrial test species. It is moderately to highly toxic to both freshwater and marine/estuarine fish, invertebrates, and freshwater algae and macrophytes. It is less toxic to marine/estuarine plants. Sedaxane is classified as practically nontoxic to nontarget terrestrial invertebrates. There were no effects observed in an acute honey bees contact study using technical sedaxane at doses of 100 µg/bee. There were, however, sublethal effects, uncoordinated movement and apathy, noted in a preliminary evaluation of a nonguideline feeding study conducted with the Vibrance formulation. The effects were evident at the limit dose of µg/bee, a NOEC was not reported. Toxicity tests were also conducted with the parasitic wasp Aphidius rhopalosiphi, predatory mites Typhlodromus pyri and Hypoaspis aculeifer, the rove beetle Aleochara bilineata, and the earthworm Eisenia fetida. No adverse effects were reported in any of these tests at residue concentrations one to two times those expected in use areas. Sedaxane is a persistent compound in the environment. It is stable to hydrolysis. Its aquatic photolysis half life, T 1/2, is 46 days. Aerobic and anaerobic aquatic mean T 1/2 s are 884 and 3,040 days respectively. Sedaxane soil surface photolysis T 1/2 s range from days with a mean of 249 days. Aerobic and anaerobic soil metabolism trials yielded mean T 1/2 s of 353 and 375 days, respectively. Terrestrial field dissipation trials yielded T 1/2 s of days with a mean of 125 days. All reported fate studies are classified as supplemental except those for aerobic and anaerobic aquatic microbial metabolism. The U.S. EPA reviewer descriptions of the individual study weaknesses suggest that the above reported T 1/2 s are likely to be underestimations of actual persistence. For example, in discussing the aerobic soil metabolism studies the U.S. EPA review author states that In general, sedaxane concentrations decrease over the first 100 days (approximate); however, after 100 days, sedaxane concentrations remain steady through study termination ( 365 days). There were also high levels of unextracted residues. In the terrestrial field dissipation trials reasons for the supplemental classifications include residues were not

13 Ms. Susan Person 13. monitored below the 20 cm depth, and analytical detection limits may have been insufficient to detect major transformation products. The reported terrestrial field dissipation rates in particular are likely to under represent sedaxane persistence. Exposure Modeling & Risk Assessment Standard BOH screening level exposure modeling was conducted for both aquatic and terrestrial nontarget resources. Nontarget organism sedaxane exposures are likely to low from this use pattern. Highly conservative screening level exposure modeling shows no toxicity should occur from sedaxane as labeled. The only exposure modeling output included in the appendix is that for screening level aquatic exposure. The highest peracre application rate was added directly to the surface of the PONDTOX model pond. No toxicity thresholds were exceeded at this exaggerated rate. Sedaxane residues will persist, carrying over at low levels from one year to the next. It is likely to show up in surface waters, again, at low concentrations. Another factor, in addition to the low application rates, that will serve to minimize field residue levels, is, as a systemic compound some portion of the applied sedaxane will be removed from the field with the treated crops. The BOH has concluded that when used as labeled, sedaxane isn t likely to result in adverse impacts to nontarget organisms and, therefore, has no objection to registration and use of the products as labeled in New York State.