November 24, 2008 CERTIFIED MAIL RETURN RECEIPT REQUESTED

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1 New York State Department of Environmental Conservation Division of Solid and Hazardous Materials Bureau of Pesticides Management, 11th Floor 625 Broadway, Albany, New York Phone: (518) FAX: (518) Website: Alexander B. Grannis Commissioner November 24, 2008 CERTIFIED MAIL RETURN RECEIPT REQUESTED Mr. Jim Baxter State Regulatory Leader Dow AgroSciences, LLC 9330 Zionsville Road Indianapolis, IN Dear Mr. Baxter: Re: Registration of the Pesticide Product Sapphire (EPA Reg. No ) Containing the New Active Ingredient Penoxsulam (Active Ingredient Code ) The Department of Environmental Conservation (Department) has evaluated your application and data package received on September 4, 2007 and additional materials received January 31, 2008 for the registration of the above-referenced product. Sapphire is an herbicide labeled for postemergence control of annual and perennial broadleaf weeds in established turfgrass, including residential lawns, golf courses, sports fields, sod farms, and around commercial buildings and other commercial turfgrass areas. Sapphire contains 3.68% of the active ingredient penoxsulam. It is to be applied using broadcast or spot application techniques. The maximum single application rate is 1.5 pints of Sapphire (0.06 pounds of penoxsulam) per acre per application. The maximum annual use rate is 2.3 pints of Sapphire (0.09 pounds of penoxsulam) per acre per year. The subject application package was deemed complete for purposes of technical review on March 31, Pursuant to the review time frame specified in Environmental Conservation Law , a registration decision date of August 28, 2008 was established. Prior to the decision date, the Department s groundwater staff communicated concerns regarding the lack of data on the transformation product SFA. Due to these concerns, the Department did not support registration at that time. Dow AgroSciences, LLC requested the Department waive the registration date to allow additional time to formulate a response to the Department s concerns. Additional information was received on October 16, The additional information sufficiently mitigated the concerns communicated by the Department. The following technical reviews were performed to evaluate the risk of the proposed use of penoxsulam on the human health and groundwater resources of New York State.

2 Mr. Jim Baxter 2. HUMAN HEALTH RISK ASSESSMENT: Neither the new active ingredient penoxsulam nor the formulated product Sapphire was very toxic in acute oral, dermal and inhalation toxicity studies. Penoxsulam was a slight skin irritant, but not an eye irritant, whereas Sapphire was neither a skin nor eye irritant (tested on rabbits). In addition, neither the active ingredient nor the formulated product was a skin sensitizer (tested on guinea pigs). Both acute and chronic neurotoxicity studies were conducted on penoxsulam. No effects were reported in an acute oral neurotoxicity study in rats at dose levels up to 2,000 milligrams per kilogram body weight (mg/kg), the highest dose tested. No signs of neurotoxicity were noted in a chronic neurotoxicity feeding study in rats up to 250 milligrams per kilogram body weight per day (mg/kg/day), also the highest dose tested. Penoxsulam caused some toxicity in subchronic (90 day) animal feeding studies. In a subchronic oral toxicity study in rats, decreases in body weight and body weight gain, decreased food consumption and decreased red blood cell parameters in males, and increased mineralization and hyperplasia of the kidney pelvic epithelium in females was reported at 250 mg/kg/day and 500 mg/kg/day, respectively. The respective no-observed-effect levels (NOELs) were 50 and 250 mg/kg/day. In mice, no adverse effects were reported up to dose levels of 1,027 mg/kg/day in males and 1,029 mg/kg/day in females. In dogs, histopathologic changes in the kidney were observed in males at 49.4 mg/kg/day and females at 57.1 mg/kg/day. The respective NOELs were 17.8 mg/kg/day and 19.9 mg/kg/day. In a 28-day dermal exposure study in rats, neither local nor systemic effects were noted at dose levels up to 1,000 mg/kg/day (the highest dose tested). Penoxsulam also caused some toxicity in chronic animal feeding studies. In a one-year dog feeding study, penoxsulam caused slight multifocal hyperplasia in the kidney epithelium in males at 46.2 mg/kg/day; the NOEL was 14.7 mg/kg/day. Penoxsulam did not cause toxic effects in female dogs at doses up to 44.8 mg/kg/day, the highest dose tested. No effects were observed in a chronic feeding study in mice up to doses of 375 mg/kg/day in males and 750 mg/kg/day in females (the highest doses tested). In a chronic feeding study in rats, penoxsulam caused decreased body weight and body weight gain, increased urine volume, increased crystals in urinary bladder, hyperplasia of kidney pelvis epithelium and urinary bladder mucosa in males and females at 250 mg/kg/day; the NOEL was 50 mg/kg/day. The U.S. Environmental Protection Agency (U.S. EPA) Office of Pesticide Programs calculated an oral reference dose (RfD) of mg/kg/day for penoxsulam based on a NOEL of 14.7 mg/kg/day in the one-year dog feeding study (slight multifocal hyperplasia in the kidney epithelium in males) 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 penoxsulam. Penoxsulam caused some developmental toxicity in the offspring of pregnant rabbits, but not pregnant rats, exposed to this chemical during organogenesis at doses that also caused maternal toxicity. In the rabbit study, an increase in the incidence of abortion and post-implantation

3 Mr. Jim Baxter 3. loss/resorptions was reported at a maternal dose of 75 mg/kg/day; the NOEL was 25 mg/kg/day. Maternal toxicity consisted of decreased body weight gain and food consumption, clinical signs of toxicity, and increased deaths and abortions at a dose of 75 mg/kg/day; the NOEL was 25 mg/kg/day. In the rat study, no treatment-related effects were observed in offspring at maternal doses up to 1,000 mg/kg/day, the highest dose tested. Maternal toxicity consisted of decreased body weight gain and food consumption and increased absolute and relative liver weights at a dose of 1,000 mg/kg/day; the NOEL was 500 mg/kg/day. In a multi-generation reproduction study in rats, penoxsulam was associated with delayed preputial separation at a dose of 100 mg/kg/day; the NOEL was 30 mg/kg/day. Parental toxicity consisted of decreased body weight in F1 males and kidney lesions in females at doses of 300 mg/kg/day for males and 100 mg/kg/day for females; the respective NOELs were 100 mg/kg/day and 30 mg/kg/day. Penoxsulam displayed evidence of carcinogenicity in one sex (male) of one species (rats) in chronic feeding/oncogenicity studies in rats and mice. There was an increased incidence of mononuclear cell leukemia (MNCL) in male rats at all dose levels. However, the tumor rates were essentially the same in all three dose groups (30, 29 and 30 in the 5, 50 and 250 mg/kg/day dose groups, respectively) compared to the control group (12). In addition, no difference in severity or "stage" was observed between the dosed groups. Due to the apparent increase in MNCL, a second peer review of the study was conducted which compared the results to newly available historical control data from the registrant and the National Cancer Institute (NCI). The peer review concluded that the increase in MNCL should not be considered toxicologically relevant because the increase in the incidence of MNCL was not dose-related and was found to be within the range of historical control data. The U.S. EPA concluded that "Although MNCL is recognized as a common neoplasm in Fischer rats, the mechanism of producing MNCL is not completely understood. Therefore, the significance of MNCL and its biological relevance for human cancer risk remains uncertain and cannot be discounted." Based on the above information, the U.S. EPA classified penoxsulam as "suggestive evidence of carcinogenicity, but not sufficient to assess human carcinogenic potential." The U.S. EPA did not recommend the quantification of cancer risk. Penoxsulam was negative in a number of genotoxicity studies. The U.S. EPA conducted a non-cancer risk assessment for exposures to penoxsulam from turf use. Since a short-term dermal toxicity endpoint was not identified for penoxsulam, only inhalation exposures were considered for assessing handler risks. For this purpose, a NOEL of 17.8 mg/kg/day from a 13-week feeding study in dogs (based on histopathological changes in the kidneys) was used. For mixer/loaders assisting in treating large turf areas (40 or 80 acres per day), margins of exposure (MOEs) ranged from 200,000 to 430,000. MOEs for applicators treating these areas using ground boom equipment ranged from 360,000 to 700,000. Mixer/loader/applicators involved in spray spot treatment of 1,000 square feet of turf per day had estimated MOEs of 26,000 to 430,000. Mixer/loader/applicators involved in treating 0.5 acres of turf per day by granular spreader had estimated MOEs of 5,600,000 to 430,000,000. Post-application exposures were estimated for children from hand-to-mouth, object-to-mouth and soil ingestion pathways of exposure. MOEs for these combined ingestion pathways for children ranged from 18,000 to 120,000 depending on which data are used to base transferable residue estimates. Inhalation was determined to be negligible for post-application exposures and no dermal toxicity endpoints were identified to assess risks by this

4 Mr. Jim Baxter 4. route. Post-application exposures were not assessed for applicators due to the negligible exposures expected from inhalation and ingestion, and because no short-term dermal toxicity endpoint was identified for penoxsulam. The U.S. EPA considered MOEs of 100-fold or greater to provide adequate protection of workers and residents from the turf use of penoxsulam. While this assessment assumed in some cases that penoxsulam was applied as granular product through a push-spreader, the Sapphire product is a liquid that is diluted and applied through "proper application equipment." There are no chemical specific federal or New York State drinking water/groundwater standards for penoxsulam. 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 available information indicates that neither penoxsulam nor the formulated product Sapphire was very acutely toxic or irritating to the skin or eyes. Data from subchronic and chronic animal studies indicate that penoxsulam has the potential to cause some toxicity, and appears to target the urinary tract. According to the U.S. EPA, this is due to penoxsulam's limited solubility in urine, which can result in crystal formation that irritates tissues in the urinary tract, and following repeated dosing, lead to numerous secondary effects. In addition, there is some limited evidence that penoxsulam has oncogenic potential in male rats and U.S. EPA has classified this compound as "suggestive evidence of carcinogenicity, but not sufficient to assess human carcinogenic potential" and did not recommend the quantification of human cancer risk. The estimated non-cancer risks to workers and the public from use of Sapphire on established turfgrass are well within the range that is generally considered to be acceptable. While penoxsulam showed some evidence of carcinogenic potential in male rats, the evidence is relatively weak. The dose-response data for MNCL are difficult to interpret and within the historical control ranges in registrant and NCI-sponsored studies. Also, penoxsulam does not appear to have genotoxic potential. The exposure potential to penoxsulam residues on treated turf sites is limited due to its relatively low application rate and low environmental persistence. Based on the application methods and statements in the product label, Sapphire appears to be marketed to professional pesticide applicators, not homeowners, which should help ensure that the product is applied properly. In addition, this product could replace lawn and turf herbicides that pose greater risk to workers and the general public. Given the above, the New York State Department of Health does not object to registration of Sapphire in New York State. ENVIRONMENTAL FATE RISK ASSESSMENT: Penoxsulam is a systemic, post-emergent herbicide belonging to the triazolopyramidine sulfonamides chemistry family. The mode of action is by inhibition of acetolactate synthase (ALS), the first enzyme in the biosynthetic pathway for several amino acids. Dow AgroSciences, LLC is applying to register penoxsulam for postemergence control of annual and perennial broadleaf weeds in established turfgrass, including residential lawns, golf courses, sports fields, sod farms, and around commercial buildings and other commercial turfgrass areas.

5 Mr. Jim Baxter 5. Sapphire contains 3.68% active ingredient (ai) or 0.31 lb ai/gallon. It is applied as a broadcast or spot treatment. It may not be applied by chemigation. The single application rate is 1.5 pints (0.06 lb ai) per acre per application, with a maximum application rate of 2.3 pints (0.09 lb ai) per acre per year. The label prohibits the use of grass clippings as mulch. The registrant stated that Sapphire is considered a reduced-risk product due to reduced risk to human health and non-target organisms, reduced potential for contamination of ground and surface waters, and for broadening the adoption of IPM while reducing environmental loading. Staff requested U.S. EPA documentation confirming this designation. Dow AgroSciences, LLC submitted a document from the U.S. EPA Registration Support Branch indicating that penoxsulam was approved as a reduced risk candidate due to the fact that it is less toxic than several currently registered alternatives and is applied at a low use rate. The inerts do not appear to be solvent carriers. Transformation Products: BSTCA 3-[[[2-(2,2-difluoroethoxy)-6-(trifluoromethyl)phenyl]-sulfonyl]amino]-1H- 1,2,4-triazole-5-carboxylic acid TPSA 5,8-dimethoxyl[1,2-4]triazolo-[1,5-c]pyrimidin-2-yl-sulfamic acid 2-Amino TP 5,8-dimethoxyl[1,2-4]triazolo-[1,5-c]pyrimidin-2-amine BSA 2-(2,2-difluoroethoxy(-5-(trifluoromethyl) benzenesulphonic acid 2-Amino TCA 2-amino-1,2-4triazole carboxylic acid D1 5-OH, 2-amino TP; 8-methoxy[1,2,4]triazolo-[1,5-c]pyrimidin-5-ol-2-amine D2 2-amino TP; 5,8-dimethoxy[1,2,4]triazolo-[1,5-c]pyrimidine-2-amine BST 2-(2,2-difluoroethyoxy)-N-1H-1,2-4-triazol-3-yl-6-(trifluoromethyl) benzenesulphonamide BSTCA-methyl methyl 5-[[[2-)2,2-difluoroethyoxy)-6-(trifluoromethyl) phenyl]sulphony]amino], 1H-1,2-4-triazole-3-carboxylic acid 5,8-diOH 2-(2,2-difluoroethoxy)-6-trifluoromethyl-N-(5,8-dihydroxy- [1,2,4]triazolo[1,5-c]pyrimidin-2-yl)benzenesulfonamide 5-OH-XDE (2,2-difluoroethoxy)-N-(5,6-dihydro-8-methoxy-5-oxo[1,2,4]triazol [1,5c]pyrimidin-2-yl)-6-(trifluoromethyl)benzenesulfomamide SFA 2-(2,2-difluoroethoxy)-N-(iminomethyl-6-(trifluoromethyl)-benzenesulfonamide Solubility: Penoxsulam has a solubility of 410 mg/l. Hydrolysis: In an acceptable study (MRID ), penoxsulam was stable in ph 5, 7 and 9 solutions as well as in natural water from the White River in Indiana (ph 8). Aqueous Photolysis: In a supplemental study (MRID ), in lake water (ph 7.8 from a lake in the UK), the half-life was 1.5 days with major transformation products TPSA, 2-amino TP, 5-OH- Amino TP, BSA and 2-amino TCA. In a supplemental study (MRID ), in an Arkansas pond water (ph unknown), the half-life was 3.1 days with major transformation products D1 and D2. In the flooded silt loam portion of the test, the half-life was 14.2 days with major transformation products BST and BSTCA-methyl.

6 Mr. Jim Baxter 6. Soil Photolysis: In a supplemental study (MRID ), the half-life in an Arkansas silt loam soil was 27 days with major transformation products BSA, BSTCA and 2-amino TP. In a Greggio silt clay loam soil, the half-life was 84 days with no major transformation products. The EFED memo indicated that the half-life was 19 and 109 days on two soils at ph 6. Anaerobic Aquatic: (MRID ) In the acceptable portion of this study, the half-life in an Arkansas pond water-silty clay sediment was 4.8 days with major transformation products 5-OH- XDE-638, BSTCA, 5,8-diOH, and BSTCA-methyl. The pond water-silt loam soil from Arkansas had a half-life of 10.5 days with major transformation products 5-OH-XDE-638 and BSTCA. In the portion of the study found supplemental, the half-life in a distilled water-silty clay loam soil from Italy was 6.6 days with major transformation products 5-OH-XDE-638 and BSTCA. The U.S. EPA Environmental Fate and Effects Division (EFED) memo indicated that the total system half-lives using linear regression of log-transformed data were 5, 7 and 11 days. Aerobic Aquatic: In an acceptable study (MRID ), the half-life in a pond water-silty clay sediment from Arkansas was 16.7 days in the water, 16.1 days in the soil and 16.3 days in the whole system. In pond water-silt loam soil from Arkansas, the half-life was 29.2 days in the water, 8.4 days in the soil and 29.1 days in the whole system. In a channel water-loam sediment from Italy, the half-life was 11.2 days in the water, 15.3 days in the soil and 12.1 days in the whole system. In a lake watersand sediment from France, the half-life was 20.9 days in the water, >99 days in the soil and 37.7 days in the whole system. In an HPLC grade water-volcanic loam soil from Japan, the half-life was 26.1 days in the water, 35.5 days in the soil and 29.9 days in the whole system. In an HPLC grade waternonvolcanic loam soil from Japan, the half-life was 21.3 days in the water, 57.5 days in the soil and 30.9 days in the whole system. Major transformation products for all systems were 5-OH-XDE-638 and BSTCA. The EFED memo indicated that the total system half-lives using linear regression of logtransformed data were 16 to 38 days. Aerobic Soil Metabolism: In a study that U.S. EPA found acceptable (MRID ): Soil ph % OM t ½ (days) Transformation Products AR silt loam OH-XDE % BSTCA 37.2% SFA 15.2%. CA clay loam OH-XDE % BSTCA 32.4% ND loam OH-XDE % BSTCA 20.6% The EFED memo indicated that the half-lives using linear regression of log-transformed data were 34, 43 and 118 days.

7 Mr. Jim Baxter 7. Adsorption/Desorption: In a study that U.S. EPA found acceptable (MRID ): Soil ph % OM Koc ads Koc des NC sand (M538) AR silt loam (M557) Japan loam (M558) Japan sandy clay loam (M559) Japan loam (M560) Japan loam (M561) CA clay loam (M562) ND loam (M563) Italy silty clay loam (M570) OC France silty clay loam (M571) OC UK sandy clay loam (M572) OC Italy sandy loam (M573) OC AR silty clay unknown unknown Brazil sandy loam (M564) Brazil clay loam (M565) Brazil sandy clay loam (M566) Canada clay loam (M567) Canada clay loam (568) In a study (MRID ) on transformation products that U.S. EPA found supplemental: Soil ph % OM Koc ads BSTCA Koc ads BST NC sand (M538) AR silt loam (M557) Koc ads 5-OH-XDE-638

8 Mr. Jim Baxter 8. CA clay loam (M562) ND loam (M563) Not provided Italy silty clay loam (M570)* France silty clay loam (M571)* UK sandy clay loam (M572)* Italy sandy loam (M573)* OC OC OC OC Not provided *The half-lives in these four soils were days for 5-OH-XDE-638, for BSTCA and 6-43 days for BST. Aged Leaching: In a study that U.S. EPA found supplemental (MRID ), no results were presented. Terrestrial Field Dissipation: In a study that U.S. EPA found acceptable (MRID ), the half-life in a California sandy loam (ph 7.2, %OM 1.0) was 18.8 days. Major transformation products were 5-OH-XDE-638 and BSTCA. In a sandy loam from Wayne County, NY (ph 6.1, %OM 2.7), the half-life was 5.9 days with major transformation product BSTCA. The study summary submitted for field transformation indicated that the transformation product 5-OH XDE-638 had a half-life of 23 days in NY and 26 days in CA. BSTCA had a half-life of 67 days in NY and 770 days in CA. EPA Comments: In the EFED memo dated January 31, 2007, the U.S. EPA indicated that penoxsulam is expected to be mobile in soil and moderately persistent in aerobic terrestrial environments, but not persistent in anaerobic environments. However, staff noted that there was no groundwater statement on the proposed label, and the registrant indicated that the active ingredient had been granted reduced-risk status for reduced potential impact of contamination to ground and surface water. Computer Modeling: Running LEACHP using Riverhead soils on the parent using a Koc of 296, a half-life of 34 days, and the maximum application rate of 0.09 lb ai/a/yr, the model projected cyclical peaks of between 1 and 5 ppt. Running BSTCA using a Koc of 46, a half-life of 118 days, and 37.2% of the maximum application rate or lb ai/a/yr, the model projected no leaching. Running 5-OH- XDE-638 using a Koc of 34, a half-life of 37 days, and 62.6% of the maximum application rate or lb ai/a/yr, the model projected peaks of 0.5 to 1.3 ppb. In response to the Department s concerns regarding the transformation product SFA, the registrant

9 Mr. Jim Baxter 9. submitted aerobic metabolism and adsorption/desorption data that were calculated for the degradate SFA. Staff ran LEACHP on degradate SFA using a half-life of 174 days, a Koc of 40, and an application rate of 15.2% of 0.09 lb ai/a/yr, or lb ai/a/yr. Modeling predicted cyclic peaks between 0.5 and 1.5 ppb for the degradate SFA. Environmental Fate Summary: The modeling assumes all of the product applied is available to leach, however, interception will occur when penoxsulam is applied to turf. The modeling projections of 1.5 ppb for SFA and 1.3 ppb for 5-OH-XDE-638 are worst case and are greater than would be expected from actual use of the product. Based on the information evaluated in the April 2, 2008 memorandum, modeling for the degradate SFA, and the fact that the product is applied to turf areas, staff do not expect this product to leach significantly into the groundwater when used as labeled on turf. Therefore, groundwater staff do not object to the registration of this product as labeled. REGISTRATION SUMMARY: The Department hereby accepts the registration of Sapphire (EPA Reg. No ) in New York State. Enclosed for your files is a copy of the stamped Accepted For Registration label and the New York State Certificate of Pesticide Registration for Sapphire. Please be reminded that this application was reviewed only for the particular use pattern and use sites presented in the Sapphire label. Specifically, Sapphire was reviewed with the expectation that the product would be marketed to professional applicators. A proposal by Dow AgroSciences, LLC or any other registrant to register a product containing penoxsulam that is intended for the homeowner market or would otherwise increase the potential for impact to New York State resources will constitute a major change in labeled use pattern. Such an application must be accompanied by a new fee and meet the application requirements specified in 6 NYCRR Part Please contact Shaun Peterson, of my staff, at (518) if you have any questions regarding this letter. Sincerely, Maureen P. Serafini Enclosures Maureen P. Serafini Director Bureau of Pesticides Management ecc: A. Grey/E. Horn, NYS Dept. of Health R. Mungari, NYS Dept. of Ag. & Markets W. Smith, Cornell University, PSUR

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