December 26, Via (Co. No ) Mr. Andrew Kieniksman ISK Biosciences Corporation 7470 Auburn Road, Suite A Concord, Ohio 44077

Transcription

1 (518) December 26, 2017 Via (Co. No ) Mr. Andrew Kieniksman ISK Biosciences Corporation 7470 Auburn Road, Suite A Concord, Ohio Dear Mr. Kieniksman: Re: Registration of the New Active Ingredient Pyriofenone Contained in the Pesticide Product Pyriofenone 300SC Fungicide (EPA Reg. No ) The New York State Department of Environmental Conservation (Department) has reviewed the application, received July 7, 2017, and additional data, received July 25, 2017, from ISK Biosciences Corporation in support of registration of the abovementioned product in New York State. The application package was deemed complete for purposes of technical review on August 24, Pursuant to the review time frame specified in Environmental Conservation Law , a registration decision date of January 19, 2018 was established. Pyriofenone 300SC Fungicide (EPA Reg. No ) contains 27.3% of the active ingredient pyriofenone ((5-chloro-2-methoxy-4-methyl-3-pyridinyl) (2,3,4- trimethoxy-6-methylphenyl) methanone) and is formulated as a suspended concentrate. Pyriofenone is a Group U8 fungicide with preventive, locally systemic and curative properties for foliar diseases. It is proposed for use on crop group 9 Cucurbit vegetable, Caneberry, Bushberry, Small Fruit Vine Climbing, and Low Growing Berry crop groups. Pyriofenone 300SC Fungicide is applied with all types of spray equipment normally used for ground and aerial applications. The proposed application rates are 4 fl. oz. to 5 fl. oz. product (0.078 to lb. a.i.) per acre and the maximum seasonal application rate is 16 fl. oz. product (0.313 lb. a.i.) per acre per year. Pyriofenone 300SC Fungicide can be used in dilute or concentrate sprays to control powdery mildew foliar diseases. REGISTRATION SUMMARY Technical reviews of the proposed uses included on the subject product label have been performed by the Department and the New York State Department of Health (DOH). These reviews encompassed the expected impacts of labeled use of the subject product with respect to human health, ecological effects, and environmental fate.

2 Mr. Andrew Kieniksman 2. The human health assessment did not result in any direct human health concerns related to the proposed registration. In addition, DOH staff recognize that there could be some potential benefit from the use of this product in New York State as an alternative rotational fungicide to manage pathogen resistance, especially for powdery mildews. The Department s Division of Fish and Wildlife s Bureau of Habitat (BOH) indicated that their exaggerated conservative exposure modeling results, using the currently available information, show a significant safety margin for pyriofenone and when used as labeled, pyriofenone should not result in adverse effects to non-target resources. The Department s environmental fate staff s review indicated that no major degradates were identified and parent pyriofenone is not expected to impact groundwater. No concerns were raised regarding the potential for pyriofenone to negatively impact the water resources of New York State. The full technical reviews of human health, ecological effects and environmental fate are presented in the Appendix of this letter. The Department concludes that the use of Pyriofenone 300SC Fungicide should not have an adverse effect on the health of applicators or the general public, or nontarget organisms, or water resources when used as labeled. Therefore, Pyriofenone 300SC Fungicide (EPA Reg. No ) has been registered in New York State. Enclosed for your record are copies of the Certificate of Pesticide Registration and the New York State stamped Accepted for Registration label. Please note that a proposal by ISK Biosciences Corporation or any other registrant to register a product that contains pyriofenone, and whose labeled uses are likely to increase the potential for significant impact on humans, non-target 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 (November 2014). Such information, as well as forms, can be accessed at our website as listed in our letterhead. Please contact Ms. Sharlin Liu, of the Pesticide Product Registration Section at (518) , if you have any questions regarding this letter. Sincerely, /S/ Scott Menrath, P.E. Director Bureau of Pest Management Enclosures

3 Mr. Andrew Kieniksman 3. HUMAN HEALTH ASSESSMENT: APPENDIX The following technical review was produced by staff within the Bureau of Toxic Substance Assessment at the New York State Department of Health (DOH): Acute Toxicity Neither pyriofenone nor the formulated product, Pyriofenone 300SC Fungicide, was very toxic in acute oral, dermal or inhalation exposure studies in laboratory animals. In addition, neither the active ingredient nor the formulated product was irritating to skin and eyes (tested on rabbits) or a skin sensitizer (tested on guinea pigs). Neurotoxicity Both acute and subchronic oral neurotoxicity studies were conducted on pyriofenone in rats. In the acute study, this chemical did not cause any adverse effects up to a dose level of 2,000 milligrams per kilogram body weight (mg/kg). Neurotoxic effects were not observed in the subchronic study, up to a dose level of 927 mg/kg/day. However, systemic effects (decreased body weight gain) was observed at 310 mg/kg/day in this study; the no-observed-effect-level (NOEL) was 62 mg/kg/day. Chronic Toxicity Pyriofenone caused some toxicity in chronic feeding studies in laboratory animals. In a chronic feeding study in dogs, pyriofenone caused increased alkaline phosphatase activity levels and decreased body weight gain at 84 mg/kg/day; the NOEL was 14 mg/kg/day. Pyriofenone caused kidney effects (soiled fur in external genital region, granular surface, cortical tubular basophilia, cortical scarring, and cortical cysts) in males in a chronic feeding/carcinogenicity study in mice at 237 mg/kg/day; the NOEL was 77.6 mg/kg/day. In a chronic feeding study in rats, pyriofenone caused increased urinary ketones in females as well as higher absolute and relative kidney and cecum weights, soiled fur in external genital region and distended large intestine in both sexes at 226 mg/kg/day; the NOEL was 43 mg/kg/day. Additionally, pyriofenone caused chronic nephropathy in females in a carcinogenicity study in rats at 46.5 mg/kg/day; the NOEL was 9.1 mg/kg/day. The U.S. Environmental Protection Agency (U.S. EPA) Office of Pesticide Programs (OPP) established a chronic oral reference dose (crfd) for pyriofenone of mg/kg/day based on the NOEL from the carcinogenicity study in rats and an uncertainty factor of 100. This crfd value has not yet been adopted by the U.S. EPA Integrated Risk Information System (IRIS). Developmental/Reproductive Toxicity Pyriofenone caused some toxicity in rats and rabbits exposed to pyriofenone in developmental toxicity studies. Although no developmental toxicity was observed in the

4 Mr. Andrew Kieniksman 4. rat study, maternal toxicity characterized by increased cecum weights was observed at 1,000 mg/kg/day; the NOEL was 300 mg/kg/day. An increased incidence in abortions (maternal and developmental effect) was observed in rabbits at 300 mg/kg/day; the NOEL was 100 mg/kg/day. In a multi-generation reproduction study in rats, pyriofenone was associated with slight decreases in body weight in the F1 generation at 334 mg/kg/day; the NOEL was 64 mg/kg/day. Parental toxicity consisted of increased liver and cecum weights, gross pathological (dark liver, large intestine distention) and histopathological (liver pigment deposition, hypertrophy, and microgranuloma) parameters at 334 mg/kg/day; the NOEL was 64 mg/kg/day. Carcinogenicity Pyriofenone did not cause oncogenic effects in rat or mouse chronic feeding studies and was negative in a number of genotoxicity studies. The U.S. EPA classified pyriofenone as not likely to be carcinogenic to humans. Dietary Risk Assessment The U.S. EPA established tolerances for pyriofenone residues in or on a number of crops and commodities (Federal Register 82(73): 18,235 40; April 18, 2017). The chronic population adjusted dose (cpad) for pyriofenone is mg/kg/day and has the same basis as the crfd. The U.S. EPA estimated that chronic dietary exposures (food and drinking water) to this active ingredient would be 1.5 percent of the cpad for the general U.S. population, 2.8 percent for infants less than 1-year old and 7.2 percent for children 1-2 years old, the highest exposed subgroup. These exposure analyses are based on the assumption that 100 percent of labeled crops are treated and contain tolerance level residues. Actual residues and resulting exposure levels are expected to be less than these assessments estimate. Occupational Risk Assessment The U.S. EPA reported the results of an occupational risk assessment for inhalation exposures to pyriofenone from the labeled use of Pyriofenone 300SC Fungicide on various field and orchard crops via several application methods (aerial, airblast, groundboom, backpack sprayer, and mechanically pressurized handgun). Dermal risks were not assessed because a dermal toxicity endpoint for pyriofenone was not identified in the toxicity database. For determining margins of exposure (MOEs), the U.S. EPA compared estimated short-term (1-30 days)/intermediate-term (30 days-6 months) inhalation exposures to a NOEL of 61 mg/kg/day from a subchronic oral toxicity study in rats (increased cecum weight in males at 150 mg/kg/day). The estimated inhalation MOEs for mixers/loaders supporting aerial, airblast, and groundboom applications to field and orchard crops ranged from 6.5 x 10 5 to 5.9 x 10 6, depending on the use site. The MOEs for applicators in these scenarios ranged from 2.6 x 10 5 to 2.9 x Short-/intermediate-term inhalation MOEs for mixers/loaders/applicators of pyriofenone using a backpack sprayer and mechanically pressurized handgun were 2.4 x 10 6 and 6.3 x 10 5, respectively. These estimates assumed workers wore personal

5 Mr. Andrew Kieniksman 5. protective equipment (long sleeved shirt and long pants, shoes plus socks and chemical-resistant gloves) as per label requirements. The U.S. EPA considered MOEs of 100-fold or greater in these scenarios to provide adequate worker protection. Drinking Water/Groundwater Standards There are no chemical specific federal or New York State drinking water/groundwater standards for pyriofenone. Based on its chemical structure, this chemical falls under the 50 micrograms per liter (µg/l) New York State drinking water standard for unspecified organic contaminants (10 NYCRR Part 5, Public Water Systems). In addition, the U.S. EPA has established a chronic, non-cancer Human Health Benchmark guideline value (i.e., level in drinking water at or below which adverse health effects are not anticipated from lifetime exposure) for pyriofenone of 600 µg/l for the general public. The U.S. EPA Benchmark guideline values have been developed for pesticide active ingredients that may be found in surface or groundwater 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. Summary The available information on pyriofenone and the formulated product Pyriofenone 300SC Fungicide indicates that they are not very acutely toxic; irritating to eyes or skin, nor a sensitizer in laboratory animal studies. Dietary administration of pyriofenone to laboratory animals in chronic, sub-chronic and developmental toxicity studies indicates that the primary target organs are the liver (dog, rat, and mouse), kidney (rat and mouse), and cecum (rat). Pyriofenone was neither teratogenic nor oncogenic and was classified by the U.S. EPA as not likely to be carcinogenic to humans. The estimated dietary risks from exposure to pyriofenone from treated crops and drinking water were within the range considered acceptable by the U.S. EPA. In addition, the expected exposure from the labeled use of the formulated product should not pose significant risks to workers. The U.S. EPA additionally reported the potential benefits from the use of pyriofenone to growers and consumers. Due to the low toxicity profile of pyriofenone, it is expected to be an alternative for other fungicides with greater concerns for toxicity (e.g. myclobutanil) which are primarily used on these crops groups. In addition, pyriofenone could potentially enhance both resistance and disease management of powdery mildews on cucurbits and berries. According to the U.S. EPA, Pyriofenone will be a very valuable fungicide in managing powdery mildews on cucurbit crops and berries and small fruits. It is likely to play a significant role is resistance management, particularly in berries and small fruits (crop group except large shrub/tree berry subgroup 13-07C), because powdery mildews have high propensity to develop resistance against fungicides.

6 Mr. Andrew Kieniksman 6. NYS DOH Recommendation The labeled use of Pyriofenone 300SC Fungicide does not appear to pose unreasonable risks to workers or the general public. In addition, DOH staff recognize that there could be some potential benefit from the use of this product in New York State as alternative rotational fungicides to manage pathogen resistance, especially for powdery mildews. Given the above, DOH staff do not object to the registration of Pyriofenone 300SC Fungicide in New York State. ECOLOGICAL EFFECTS ASSESSMENT: The following technical review was produced by the Department s staff within the Bureau of Habitat (BOH): I. CHEMICAL BACKGROUND Pyriofenone, (5-chloro-2-methoxy-4-methyl-3-pyridinyl) (2,3,4-trimethoxy-6- methylphenyl) methanone, is a new fungicidal aryl-phenyl-ketone type compound with preventative and curative action. It is a Group U8 fungicide currently labeled for powdery mildew control on a limited number of crop groups. Use Profile Pyriofenone 300SC Fungicide is labeled for use on: Cucurbit, Caneberry, Bushberry, Small Fruit Vine Climbing, and Low Growing Berry crop groups. The most significant potential labeled uses in New York State are on Grape, Blueberry, and Strawberry. Applications of 4-5 fluid ounces formulated product per acre, equaling lb. active ingredient per acre (lb. a.i./a), are made using water as the carrier. Repeat applications are made at 7-10 day intervals on all crops except grapes where the interval is 14 days. No more than 2 sequential applications of Pyriofenone 300SC Fungicide are allowed before switching to a fungicide with a different mode of action. No more than 16 fluid ounces formulation per acre, lb. a.i./a, may be applied per year. Applications may be made with ground or aerial spray equipment. Mode of Action The mode of action of pyriofenone isn t well defined but it is thought to disrupt cellular action in some manner. Physical/Chemical Properties The reported physical and/or chemical characteristic values used herein for pyriofenone are given in the following table.

7 Mr. Andrew Kieniksman 7. Table 1. Physical/Chemical Characteristics Solubility in water 1.56 mg/l Log KOW 3.2 Density 1.36 g/ml Vapor pressure 1.4 x 10-8 mmhg Soil organic carbon partitioning coefficient KOC = , Geometric mean=1303 ml/g II. TOXICITY Pyriofenone was practically nontoxic in the submitted bird and mammal toxicity tests in both acute and chronic trials. It is not acutely toxic to fish or fresh water Daphnia up to its water solubility limit. There were no mortalities or sub-lethal effects observed in the submitted acute studies. It is moderately to highly toxic to marine invertebrates and all algae. Acute and chronic study results were reported for both adult and larval honey bees. In all studies, pyriofenone is classified as practically nontoxic. Results for one adult chronic test were ambiguous due to sporadic mortality that was not dose dependent. III. EXPOSURE Pyriofenone is a persistent compound that degrades primarily via microbial metabolism and to a lesser degree through aquatic photolysis. It is stable to hydrolysis. Its aquatic photolysis half-life, T1/2, is 20 days in natural waters and is 33 days in purified water. This indicate that organic photosensitizers facilitate degradation. The soil photolytic T1/2 is 186 days. In laboratory aerobic soil metabolism study, T1/2s ranged from 49 to 75 days with a geometric mean of 71 days. In anaerobic soil metabolism laboratory study, T1/2s ranged from 29 to 48 days with a geometric mean of 35 days. The applied parent compound remained as unextracted residues was 18%-45% in the aerobic studies and 59%-85% in the anaerobic studies. The levels of applied parent compound in unextracted material suggest that the reported T1/2s may be underestimating the actual degradation rate. Two sediment/water system dissipation studies were submitted: The United Kingdom (UK) study systems and the United States (U.S.) study systems. In the UK study systems, the aerobic study was conducted using two different lakes (lake one: Calwich Abbey Lake; lake two: Swiss Lake) as water/sediment sources. In the U.S. study systems, the anaerobic study was conducted using two different U.S. (Massachusetts) rivers as sediment/water sources. The (radiolabeled) pyriofenone was applied to the water column from which it rapidly partitioned to the sediments in both studies. The study using UK aerobic study systems showed that pyriofenone dissipation rates from the water column in the two lakes were different from each other. No water column DT50s or T1/2 values were stated. Instead, the study reported the percentages of pyriofenone remaining in water column at

8 Mr. Andrew Kieniksman 8. different sampling time: only 42% of the applied radioactivity, (AR), remained after 1 day in the lake one water column, and 64% of AR remained at 7 days and 36% of AR remained at day 14 in the lake two water column. The UK aerobic study reported Total System DT50 times (DT50s), time to observed 50% dissipation, of 5 days (lake one) and 14 days (lake two). In the U.S. anaerobic study systems, the water column DT50s were given as 11.3 days and 12.8 days. The Total System DT50s for the same systems were approximately 14 day and 17 days respectively. The primary route of pyriofenone dissipation in these studies is partitioning to sediments where it largely remains as unextracted residues. In the UK aerobic study, 48% (lake one) and 64% (lake two) of the AR remained as unextracted residues at study termination. In the U.S. anaerobic study, at study termination, 70% and 80% of the AR remained as unextracted residues in the two river sediments. Four Terrestrial Field Dissipation study DERs were submitted, one each for trials in Washington State, California, North Carolina, and North Dakota. Calculated T1/2s ranged from 154 to 623 days with a geometric mean of 308 days. Parent compound carryover at one year ranged from 13% to 46% of applied. Pyriofenone primarily remained in the top 6-inch soil layer with only 3 detections at slightly deeper depths. Transformation products, runoff, volatilization, and plant uptake were not measured in any of the trials. Pyriofenone application rates are low. Food item residue exposure of terrestrial non-target organisms is correspondingly low. Parent compound that reaches aquatic systems in solution rapidly partitions to sediments. Prolonged exposures for most aquatic organisms are not expected. Exposure Modeling Standard highly conservative BOH screening level exposure modeling was conducted for terrestrial and aquatic non-target organisms. For terrestrial food item residue screening, the seasonal maximum application rate was applied in one application. Even at this exaggerated rate, no avian or mammalian feeding toxicity thresholds were exceeded. The surface water Direct Application module was set to simulate an application at the highest label single application rate. At this rate in the 1-foot model pond depth, the Blue-green algae NOEC was exceeded. In the 6-inch depth, the NOECs for Blue-green algae and the fresh water green algae were exceeded. The runoff module parameters were set to simulate runoff to the model pond following an application of the seasonal maximum rate in one application. All water from a 1-inch rain event was allowed to reach the pond. Under these exaggerated conditions, no aquatic toxicity thresholds were exceeded.

9 Mr. Andrew Kieniksman 9. IV. RISK ASSESSMENT Pyriofenone, when used as labeled, should not result in adverse effects to nontarget resources. The exaggerated conservative exposure modeling results, using the information currently available, show a significant safety margin for pyriofenone as currently labeled. The BOH staff has no objection to the registration of Pyriofenone 300SC Fungicide in New York State. Data Gaps & Uncertainties Toxicity data for fresh water sediment associated invertebrates is limited to a single 28-day Chironomid riparius study. A Hyalella azteca Life-cycle study is reported but it was deemed invalid by reviewers because no NOAEC was established and there were confounding effects from a solvent used. The limited amount of data and the fact that pyriofenone adsorbs and persists to sediments make it unclear what the risk to fresh water sediment dwelling invertebrates is from labeled use. ENVIRONMENTAL FATE ASSESSMENT: The following technical review was produced by the Department s Environmental Fate staff within the Bureau of Pest Management: In each section that follows, the corresponding USEPA study Guideline number, the title of the study, and the EPA MRID No, will be included for reference. 1. Guideline No , Sediment and Soil Adsorption/Desorption Batch Equilibrium, MRID The adsorption/desorption study using pyriofenone was performed using the five soils from the United Kingdom (U.K.), which are listed in the following table. Regarding the Bromsgrove sandy loam soil s ph and percent organic carbon (bolded type in table below), this is the best match for Riverhead, NY soil ((ph 5.5, % organic carbon (OC) 1%)) so the corresponding Koc value will be used in subsequent LEACHP modeling. It was noted was that there was no correlation with adsorption and soil ph and the study is classified as being scientifically sound but upgradable. Soil Type ph % OC Adsorption Kfoc (ml/g) Bromsgrove sandy loam, UK Calke sandy loam, UK Elmton sandy clay loam, UK Evesham 3 clay loam, UK Warsop loamy sand, UK

10 Mr. Andrew Kieniksman Guideline No , Aqueous Hydrolysis, MRID Pyriofenone was found to be hydrolytically stable in aqueous buffer solutions at ph 4, 7, and 9, which are at environmentally relevant acidic, neutral and alkaline ph. This indicates that hydrolysis is not a significant pathway for the environmental transformation of pyriofenone in water. The study was found to be acceptable and satisfies the guideline requirement for hydrolysis study. 3. Guideline No , Aqueous Photolysis, MRID The photolytic half-life of pyriofenone was estimated to be 20 days in natural waters and 33 days in purified water at 40 N. latitude under midsummer sunlight. The tested concentration was 0.7 mg/l, which is approximately half the reported aqueous solubility. There were no major degradates (>10% originally applied) products found post-treatment. It is noted that photolysis is not likely to be a significant route of environmental degradation for pyriofenone. 4. Guideline No , Photodegradation in Soil, MRID The soil used in this study was the Calke sandy loam from the U.K. with ph 5.7 and 3.5 %OC. The predicted environmental photolytic half-life of pyriofenone in soil was calculated to be 186 equivalent days of summer at 40 N. latitude. There were up to six minor but no major photo-transformation products detected in this study. It would not be expected that photolysis on soil would be a major transformation pathway for pyriofenone. 5. Guideline No , Aerobic Soil Metabolism, MRID Three soils from the U.K. were used in this study and the properties of these soils are listed in the following table. The amount of pyriofenone that was applied to the soils was 0.89 lbs. a.i./acre, which is approximately three times the maximum labeled rate per season. There were no major transformation products detected. Because the Bromsgrove soil s ph and %OC is most similar to Riverhead, NY soil (bolded type in the table below), that half-life will be used in subsequent LEACHP modeling. Soils Type Soil ph Soil %OC t½ (Days) Bromsgrove sandy loam Evesham 3 clay loam Elmton clay loam This study is classified as scientifically sound and upgradable.

11 Mr. Andrew Kieniksman Guideline No , Anaerobic Aquatic Metabolism, MRID The anaerobic biotransformation of pyriofenone was studied in two natural (US) aquatic sediment systems under anaerobic laboratory conditions. The following table lists the properties of these two systems: Water Soil Type and Origin Sediment ph Sediment %OC t½ Total System (Days) Taunton River sediment, silt loam Weweantic River sediment, sand In the Taunton River system, the major transformation product 2MDPM was detected at 13.5% on day 28. 3HDPM was also found at 10.4% on day 14. In the Weweantic River system, 2MDPM was found at 11.3% and 3HDPM was found at 11.4%, both on day 28. At the end of the 100-day study, 2MDPM was at 6.6 and 4.8 in the two systems, respectively. These two products are the result of an -O-CH3 group on the parent molecule being reduced to a hydroxyl -OH. The major parent molecular structure was still intact and sediment bound residues increased to about 80% of the applied throughout the incubation period. 7. Guideline No , Aerobic Aquatic Metabolism, MRID The fate of pyriofenone was studied in two natural aquatic sediment systems under aerobic laboratory conditions and the properties of these systems are listed in the following table: Water Soil Type and Origin Sediment ph Sediment %OC System t½ (Days) Swiss Lake sand, Derbyshire, U.K Calwich Abby Lake silt loam, Derbyshire, U.K The parent pyriofenone dissipated rapidly from the overall aerobic water/sediment systems and it was noted that pyriofenone adsorption to the sediments played a major role in the dissipation. There were no major transformation products detected in the study and those minor transformation products that were identified were structurally similar to the parent. This study was classified as supplemental. 8. Guideline No , Terrestrial Field Dissipation, MRIDs The parent pyriofenone was applied four times at lbs. a.i./acre to determine the dissipation and mobility of residues under field conditions. Residues

12 Mr. Andrew Kieniksman 12. declined to ppm by day 540 after the last application. Pyriofenone did not move below 12 inches except in one replicate of three at inches on day 420. The primary reviewer calculated the half-life to be on 275 days, which indicates that pyriofenone is persistent in the soil. No major transformation products were tracked in this study but it is noted that this deficiency does not invalidate the dissipation of the parent under field conditions. Residues at the end of the first year and at the end of the study has a potential for accumulation and carryover into the following crop season. MRID Soil Type and Location t½ in Surface Soil (Days) Max Depth Detected and Days Major Transformation Products Dissipation Routes Bare ground, sandy/loamy sandy soil, Ephrata, WA inches at 420 days Not tracked in study na 9. Guideline No , Terrestrial Field Dissipation, MRIDs The parent pyriofenone was applied four times lbs. a.i./acre to determine the dissipation and mobility of residues under field conditions. Residues declined to ppm by day 546 after the last application. Pyriofenone did not move below 6 inches except in one replicate of three at 6-12 inches on day 91. The calculated the half-life of 154 days indicates that pyriofenone can be regarded as moderately persistent in this soil type. No major transformation products were tracked in this study but it is noted that this deficiency does not invalidate the dissipation of the parent under field conditions. Pyriofenone has the potential for residue carryover to the following crop season. MRID Soil Type and Location t½ in Surface Soil (Days) Max Depth Detected and Days Major Transformation Products Dissipation Routes Bare ground, sandy loam soil, Kerman, CA inches at day 91 Not tracked in study na 10. Guideline No , Terrestrial Field Dissipation, MRIDs The parent pyriofenone was applied four times lbs. a.i./acre to determine the dissipation and mobility of residues under field conditions. Residues declined to ppm on day 541 after the last application. There were no residues above the LOD in samples below 3-6 inch layers. The calculated the half-life of 323 days indicates that pyriofenone can be regarded as persistent in this soil type. No major transformation products were tracked in this study but it is noted that this deficiency does not invalidate the dissipation of the parent under field conditions. Pyriofenone has the potential for residue carryover to the following crop season.

13 Mr. Andrew Kieniksman 13. MRID Soil Type and Location t½ in Surface Soil (Days) Max Depth Detected and Days Major Transformation Products Dissipation Routes Bare ground, loamy sandy soil, Seven Springs, North Carolina inches at any sampling period Not tracked in study na 11. Guideline No , Terrestrial Field Dissipation, MRIDs The parent pyriofenone was applied four times lbs. a.i./acre to determine the dissipation and mobility of residues under field conditions. Residues declined to and ppm on days 630 and 665, respectively, after the last application. With one exception, there were no residues above the LOD in samples below 3-6 inch layers. The calculated the half-life of 289 days indicates that pyriofenone can be regarded as persistent in this soil type. No major transformation products were tracked in this study but it is noted that this deficiency does not invalidate the dissipation of the parent under field conditions. Pyriofenone has the potential for residue carryover to the following crop season. MRID Soil Type and Location t½ in Surface Soil (Days) Max Depth Detected and Days Major Transformation Products Dissipation Routes Bare ground, loamy soil, Northwood, North Dakota 289 One sample at 6-12 inches at day 370 Not tracked in study na 12. Guideline No , Terrestrial Field Dissipation, MRIDs The parent pyriofenone was applied to four bare soil sites with one untreated control site as four applications. Residues declined to ppm on day 546 after the last application. Pyriofenone did not move below 6 inches except in one replicate of three at 6-12 inches on day 91. The calculated the half-life of 154 days indicates that pyriofenone can be regarded as moderately persistent in this soil type. No major transformation products were tracked in this study but it is noted that this deficiency does not invalidate the dissipation of the parent under field conditions. Pyriofenone has the potential for residue carryover to the following crop season. MRID Soil Type and Location t½ in Surface Soil (Days) Max Depth Detected and Days Major Transformation Products Dissipation Routes Bare ground, sandy loam, Kerman, CA inches at day 91 Not tracked in study na

14 Mr. Andrew Kieniksman LEACHP Modeling of Pyriofenone As was noted in the previous relevant sections, the following inputs will be used for the LEACHP modeling. There were no major degradates in the aforementioned sections so only the parent pyriofenone will be modeled. New Active Water Solubility (mg/l) Maximum Seasonal Application Rate (lbs ai/acre/yr) Aerobic Soil Half-Life (Days) Adsorption Koc (ml/g) Pyriofenone Environmental Fate Conclusion Pyriofenone was LEACHP modeled using the Riverhead, NY soil series and it is shown in the following LEACHP modeling profile that there is a maximum leaching output at 2.34E-6 µg/l (ppb) ( ppb). As a result of the above environmental fate review findings and subsequent LEACHP modeling output, the environmental fate reviewer does not object to pyriofenone being registered as a new active ingredient in New York State.