Document ID: EPA-HQ-OPP-2017-0429-0003
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2017-11-27T05:00Z

NOTICE OF FILING OF A PESTICIDE PETITION
                                       
                                       
EPA Registration Division contact: Hope Johnson, 703-305-5410	

I. E. I. du Pont de Nemours and Company

EPA has received a pesticide petition (7F8557) from E. I. du Pont de Nemours and Company, Chestnut Run Plaza, 974 Centre Road, Wilmington, Delaware, 19805 proposing, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180.669 by establishing a tolerance for residues of picoxystrobin in or on the raw agricultural commodities of Vegetable, Root (Crop Subgroup 1A) at 0.6 ppm; Vegetable, Tuberous and Corm (Crop Subgroup 1C) at 0.06 ppm; Vegetable, Leaves of Root and Tuber (Crop Group 2) at 40.0 ppm; Onion, Bulb (Crop Subgroup 3-07A) at 0.8 ppm; Onion, Green (Crop Subgroup 3-07B) at 15.0 ppm; Vegetable, Leafy except Head Lettuce (Crop Group 4-16) at 60.0 ppm; Head Lettuce at 7.0 ppm: Vegetable, Brassica Head and Stem (Crop Group 5-16) at 5.0 ppm, Vegetable, Legume, Edible Podded (Crop Subgroup 6A) at 4.0 ppm; Pea and Bean, Succulent Shelled (Crop Subgroup 6B) at 3.0 ppm; Vegetable, Fruiting (Crop Group 8-10) at 1.5 ppm; Vegetable, Cucurbit (Crop Group 9) at 0.7 ppm; Tree Nut except Hulls (Crop Group 14-12) at 0.15 ppm; Almond Hulls at 15.0 ppm; Sunflower (Crop Subgroup 20B) at 3.0 ppm; Cottonseed (Crop Subgroup 20C) at 4.0 ppm; Cotton, Gin By-Products at 40.0 ppm; Vegetable, Leaf Petiole (Crop Subgroup 22B) at 40.0 ppm; Alfalfa, Seed at 9.0 ppm; Alfalfa, Forage at 4.0 ppm; Alfalfa, Hay at 5.0 ppm; Peanut at 0.1 ppm; Peanut, Hay at 40.0 ppm; Grass, Forage (Grown for Seed) at 40.0 ppm; and Grass, Hay (Grown for Seed) at 80.0 ppm. EPA has determined that the petition contains data or information regarding the elements set forth in section 408(d)(2) of the FFDCA; however, EPA has not fully evaluated the sufficiency of the submitted data at this time or whether the data supports granting of the petition.  Additional data may be needed before EPA rules on the petition.

A. Residue Chemistry
      
1. Plant metabolism: The metabolism of picoxystrobin in plants is adequately understood. Studies have been previously evaluated by EPA which delineate the metabolism of radiolabeled picoxystrobin in apples, canola, soybeans, and winter wheat, all showing similar results.  Additional studies which delineate the metabolism of radiolabeled picoxystrobin in tomato and potato show similar results.

Picoxystrobin metabolism in tomato was investigated using two 14C-labeled versions of the test material: [phenyl(U)-14C] and [pyridine-3-14C] picoxystrobin. Picoxystrobin metabolism in tomato plants was extensive. Overall metabolic reactions included ester hydrolysis, O demethylation, conjugation, ether cleavage, and to a lesser extent, isomerization. Metabolism of picoxystrobin's side chain proceeded through a series of hydrolytic, reductive, oxidative, and/or conjugation steps yielding IN-QDY62, IN-QGS46 glucoside (only trace levels of IN-QGS46 were detected by LC-MSMS), and IN-QDY63. The pyridol cleavage product, IN-QDK50, was not observed but was detected as its glucoside, IN-QGS45. The phenyl portion of the molecule underwent extensive side chain metabolism to ultimately give the benzoic acid metabolites, IN-H8612 and phthalic acid (IN-K2122). The metabolic pathway of picoxystrobin in tomato plants is adequately understood and is consistent overall with metabolism observed in other plants.

Picoxystrobin metabolism in potato plants was investigated using two 14C-labeled versions of the test material: [phenyl-14C(U)] and [pyridine-3-14C] picoxystrobin.  Picoxystrobin metabolism in potatoes was extensive. Overall metabolic reactions included a series of reductive and/or oxidative steps (hydroxylation, O-demethylation, ester, and ether hydrolysis) on picoxystrobin's side-chain yielding IN-QDY62, IN-QDY63, IN-QGS44, IN-QGS46, IN-QGU70 acid, IN-QGU66, IN-QGU70, and IN-U3E08. Other metabolic reactions included hydrolytic cleavage to yield IN-QDK50 (pyridine label only), IN-H8612 (phenyl label only), and IN-K2122 (phenyl label only). Conjugates (glucose, malonyl glucose, HMG glucose, or homocysteine) of IN-QGS46, hydroxylated IN-QDY62, and IN-QGU70 were also observed. Picoxystrobin metabolism in potatoes was consistent with metabolism observed in other picoxystrobin plant metabolism studies.

2. Analytical method: Adequate analytical methodology is available for enforcement purposes.

An analytical method was developed, independently validated and previously evaluated by EPA for the detection and quantification of picoxystrobin and metabolites in various crop matrices. The method was validated at 0.010 and 0.10 ppm in all matrices using an LC/MS/MS system operating with an electrospray interface (ESI) in positive ion mode.  The analytical method is suitable for enforcement/monitoring and data generation for regulatory studies.  
3. Magnitude of Residue: Magnitude of residue and processing trials were conducted on carrot, radish, potato, sugarbeet, turnip, bulb onion, green onion, head lettuce, leaf lettuce, spinach, mustard greens, broccoli, cauliflower, cabbage, celery, edible podded beans, edible podded peas, succulent beans, succulent peas, tomato, bell peppers, non-bell peppers, cucumbers, melons, squash, almonds, pecans, cotton, sunflower, alfalfa, peanut, and grass grown for seed.  The resulting data supports the proposed tolerances.

 Root, Tuberous and Corm Vegetables:  The proposed labeled use of picoxystrobin on root, tuberous and corm vegetables, which will currently be limited to potato and sugar beet, allows for multiple applications not to exceed a total application of 0.585 lb a.i./acre, a maximum single application of 0.195 lb a.i./acre to potato, a maximum single application of 0.309 lb a.i./acre to sugar beet, a minimum 5-day retreatment interval (RTI) with no more than two sequential applications before switching to a fungicide with a different mode of action, and a preharvest interval (PHI) of 3-days for all commodities. Sixty trials were conducted to determine the magnitude and decline of picoxystrobin residues when applied to carrot, radish, sugar beet, potato and turnip consistent with the proposed use pattern.  In-furrow application trials were also conducted but this labeled use is not being pursued.  Six additional trials were conducted to determine the magnitude of residues of picoxystrobin in processed fractions of potato and sugar beet following application at up to more than 7X maximum proposed label rates. Proposed tolerances on the Root Vegetable Crop Subgroup 1A, Tuberous and Corm Vegetable Crop Subgroup 1C, and Leaves of Root and Tuber Vegetables Crop Group 2, are consistent with the findings of these trials.
   
 Bulb Vegetables:  The proposed labeled use of picoxystrobin on bulb vegetables which will currently be limited to garlic, bulb onion and green onion, allows for multiple applications not to exceed a total application of 0.585 lb a.i./acre, a maximum single application of 0.195 lb a.i./acre, a minimum 5-day retreatment interval (RTI) with no more than two sequential applications before switching to a fungicide with a different mode of action, and a preharvest interval (PHI) of 0-days for all commodities.  Nineteen field trials were conducted to determine the magnitude and decline of picoxystrobin residues when applied to bulb onion and green onion consistent with the proposed use pattern.  Proposed tolerances on the Bulb Onion Crop Subgroup 3-07A, and Green Onion Crop Subgroup 3-07B are consistent with the findings of these trials.
   
 Leafy Vegetables:  The proposed labeled use of picoxystrobin on leafy vegetables which will currently be limited to head lettuce, allows for multiple applications not to exceed a total application of 0.39 lb a.i./acre, a maximum single application of 0.195 lb a.i./acre, a minimum 5-day retreatment interval (RTI) with no more than two sequential applications before switching to a fungicide with a different mode of action, and a preharvest interval (PHI) of 0-days.  Forty field trials were conducted to determine the magnitude and decline of picoxystrobin residues when applied to head lettuce, leaf lettuce, spinach, and mustard greens consistent with the proposed use pattern.  Proposed tolerances on Leafy Vegetables Crop Group 4-16 are consistent with the findings of these trials.

 Brassica, Head and Stem Vegetables:  The proposed labeled use of picoxystrobin on brassica, head and stem vegetables which will currently be limited to broccoli, cabbage and cauliflower, allows for multiple applications not to exceed a total application of 0.39 lb a.i./acre, a maximum single application of 0.195 lb a.i./acre, a minimum 5-day retreatment interval (RTI) with no more than two sequential applications before switching to a fungicide with a different mode of action, and a preharvest interval (PHI) of 0-days. Twenty-one field trials were conducted to determine the magnitude of picoxystrobin residues when applied to broccoli, cauliflower, and cabbage consistent with the proposed use pattern.  Proposed tolerances on Vegetable, Brassica, Head and Stem Crop Group 5-16 are consistent with the findings of these trials.

 Succulent Legume Vegetables:  The proposed labeled use of picoxystrobin on legume vegetables, pea and bean, edible podded and succulent, allows for multiple applications not to exceed a total application of 0.39 lb a.i./acre, a maximum single application of 0.195 lb a.i./acre, a minimum 5-day retreatment interval (RTI) with no more than two sequential applications before switching to a fungicide with a different mode of action, and a preharvest interval (PHI) of 0-days. Forty field trials were conducted to determine the magnitude of picoxystrobin residues when applied to edible podded peas and beans, and succulent peas and beans consistent with the proposed use pattern.  Proposed tolerances on Vegetable, Legume, Edible Podded Crop Subgroup 6A, and Pea and Bean, Succulent Shelled Crop Subgroup 6B are consistent with the findings of these trials.

 Fruiting Vegetables: The proposed labeled use of picoxystrobin on fruiting vegetables which will be currently limited to peppers and tomato, allows for multiple applications not to exceed a total application of 0.39 lb a.i./acre, a maximum single application of 0.195 lb a.i./acre, a minimum 5-day retreatment interval (RTI) with no more than two sequential applications before switching to a fungicide with a different mode of action, and a preharvest interval (PHI) of 0-days.  Forty-four trials were conducted to determine the magnitude and decline of picoxystrobin residues when applied to tomato, bell pepper and non-bell pepper consistent with the proposed use pattern.  Three additional trials were conducted to determine the magnitude of residues of picoxystrobin in processed fractions of tomato following application at more than 9X maximum proposed label rates.  Proposed tolerances on Fruiting Vegetables Crop Group 8-10 are consistent with the findings of these trials.

 Cucurbit Vegetables: The proposed labeled use of picoxystrobin on cucurbit vegetables which will be currently limited to cantaloupe, cucumber, squash and watermelon, allows for multiple applications not to exceed a total application of 0.39 lb a.i./acre, a maximum single application of 0.195 lb a.i./acre, a minimum 5-day retreatment interval (RTI) with no more than two sequential applications before switching to a fungicide with a different mode of action, and a preharvest interval (PHI) of 0-days. Thirty trials were conducted to determine the magnitude of picoxystrobin residues when applied to cucumber, melon, and summer squash consistent with the proposed use pattern.  Proposed tolerances on Cucurbit Vegetables Crop Group 9-10 are consistent with the findings of these trials.

 Tree Nuts: The proposed labeled use of picoxystrobin on tree nuts, which will currently be limited to almonds, pistachios filberts, pecans and walnuts, allows for multiple applications not to exceed a total application of 0.585 lb a.i./acre, a maximum single application of 0.195 lb a.i./acre, a minimum 5-day retreatment interval (RTI) with no more than two sequential applications before switching to a fungicide with a different mode of action, and a preharvest interval (PHI) of 7-days for all commodities.  Twelve trials were conducted to determine the magnitude of picoxystrobin residues when applied to almond and pecan consistent with the proposed use pattern.  Proposed tolerances on Tree Nuts Crop Group 14-12, and Almond Hulls are consistent with the findings of these trials.

 Sunflower: The proposed labeled use of picoxystrobin on sunflower allows for multiple applications not to exceed a total application of 0.585 lb a.i./acre, a maximum single application of 0.195 lb a.i./acre, a minimum 5-day retreatment interval (RTI) with no more than two sequential applications before switching to a fungicide with a different mode of action, and a preharvest interval (PHI) of 7-days.  Eleven trials were conducted to determine the magnitude and decline of picoxystrobin residues when applied to sunflower consistent with the proposed use pattern.  Proposed tolerances on Sunflower Crop Subgroup 20B are consistent with the findings of these trials.

 Cotton: The proposed labeled use of picoxystrobin on cotton allows for multiple applications not to exceed a total application of 0.39 lb a.i./acre, a maximum single application of 0.195 lb a.i./acre, a minimum 5-day retreatment interval (RTI) with no more than two sequential applications before switching to a fungicide with a different mode of action, and a preharvest interval (PHI) of 7-days.  Thirteen trials were conducted to determine the magnitude of picoxystrobin residues when applied to cotton consistent with the proposed use pattern.  Proposed tolerances on Cottonseed Crop Subgroup 20C, and Cotton Gin-By-Products are consistent with the findings of these trials.

 Leaf Petiole Vegetables: The proposed labeled use of picoxystrobin on leaf petiole vegetables which will be currently limited to celery, allows for multiple applications not to exceed a total application of 0.39 lb a.i./acre, a maximum single application of 0.146 lb a.i./acre, a minimum 5-day retreatment interval (RTI) with no more than two sequential applications before switching to a fungicide with a different mode of action, and a preharvest interval (PHI) of 0-days.  Twelve trials were conducted to determine the magnitude and decline of picoxystrobin residues when applied to celery consistent with the proposed use pattern.  Proposed tolerances on Leaf Petiole Vegetables Crop Subgroup 22B are consistent with the findings of these trials.

 Alfalfa: The proposed labeled use of picoxystrobin on alfalfa allows for multiple applications not to exceed a total application of 0.585 lb a.i./acre, a maximum single application of 0.195 lb a.i./acre, a minimum 5-day retreatment interval (RTI) with no more than two sequential applications before switching to a fungicide with a different mode of action, and a preharvest interval (PHI) of 14-days.  Seventeen trials were conducted to determine the magnitude of picoxystrobin residues when applied to alfalfa consistent with the proposed use pattern.  Proposed tolerances on Alfalfa Seed, Alfalfa Forage, and Alfalfa Hay are consistent with the findings of these trials.

 Peanut: The proposed labeled use of picoxystrobin on peanut allows for multiple applications not to exceed a total application of 0.585 lb a.i./acre, a maximum single application of 0.195 lb a.i./acre, a minimum 5-day retreatment interval (RTI) with no more than two sequential applications before switching to a fungicide with a different mode of action, and a preharvest interval (PHI) of 7-days.  Thirteen trials were conducted to determine the magnitude of picoxystrobin residues when applied to peanut consistent with the proposed use pattern.  Proposed tolerances on Peanut and Peanut Hay are consistent with the findings of these trials.

 Grass Grown for Seed: The proposed labeled use of picoxystrobin on grass grown for seed allows for multiple applications not to exceed a total application of 0.585 lb a.i./acre, a maximum single application of 0.195 lb a.i./acre, a minimum 5-day retreatment interval (RTI) with no more than two sequential applications before switching to a fungicide with a different mode of action, and  preharvest intervals (PHIs) of 0-days for forage following one application, and 0-days for hay following multiple applications.  Nine trials were conducted to determine the magnitude of picoxystrobin residues when applied to grass grown for seed consistent with the proposed use pattern.  Proposed tolerances on Grass Forage Grown for Seed, and Grass Hay Grown for Seed are consistent with the findings of these trials.

B. Toxicological Profile
      
1. Acute Toxicity:  EPA has previously concluded that picoxystrobin has low to moderate acute toxicity via the oral, dermal, and inhalation routes of exposure (Toxicity Categories II-IV). Picoxystrobin is not a dermal irritant or sensitizer.  Picoxystrobin was initially evaluated to be a severe eye irritant based on a default assumption, but subsequent reevaluation concluded that picoxystrobin was a moderate eye irritant (Toxicity Category III). Acute toxicity studies for picoxystrobin technical support an overall toxicity Category II.
      
2. Genotoxicty:  EPA has previously evaluated a complete battery of immunotoxicity, mutagenicity and genotoxicity studies with picoxystrobin and concluded that Picoxystrobin has no effects on the immune system in rats and mice, and is not mutagenic or genotoxic. 

3. Reproductive and Developmental Toxicity: EPA has previously concluded that in the rat and rabbit developmental toxicity studies, developmental toxicity was expressed as skeletal variations at doses causing maternal toxicity (i.e. diarrhea, decreased body weight, body weight gain, food consumption, and clinical signs of toxicity). In the reproduction study, parental/systemic toxicity manifested as decreased body weight and body weight gain in both the parents and offspring; no reproductive toxicity was seen.

4. Subchronic toxicity: EPA has previously evaluated a subchronic toxicity feeding study with rats over 90 days, a subchronic toxicity feeding study in mice over 90 days, a subchronic toxicity feeding study in dogs, and two 28-day dermal toxicity studies in rats.  The most consistently observed effects of picoxystrobin exposure across species, genders, and treatment durations were decreased body weight, body weight gain and food consumption, and diarrhea. The effects on body weight and food consumption were consistent with the commonly observed findings for compounds which disrupt mitochondria respiration system and the resulting disruption of energy production. Similar to some other strobilurins, picoxystrobin causes intestinal disturbance as indicated by increased incidence of diarrhea or duodenum mucosal thickening.

5. Chronic toxicity:  EPA has previously evaluated two 24-month chronic/oncogenicity feeding studies in rats, two 80-week carcinogenicity studies in the mouse, and a one year feeding study with dogs.  EPA concluded from the one-year feeding study with dogs an NOAEL of 4.6 mg/kg/day as a Chronic Dietary Point of Departure; uncertainty/FQPA safety factors of 10X UFA, 10X UFH, and 1X FQPA; a chronic RfD=0.046 mg/kg/day and chronic PAD=0.046 mg.kg/day.  An LOAEL of 15.7 mg/kg/day is based on decreased body weights, body weight gains, and food consumption in both sexes. 
6. Neurotoxicity: Picoxystrobin caused changes in behavioral effects in both the acute and subchronic neurotoxicity studies with no neuropathological findings. The effects observed with acute exposure were transient (i.e. lasted for a day) and consisted of low arousal and decreased motor activities in males and decreased rearing in females, and with subchronic exposure included decreased male forelimb grip and increased female hindlimb splay. In the absence of any neuropathological findings, the behavioral effects were attributed to general malaise (probably related to energy production perturbations) as evidenced by the associated decreased body weight and body weight gain.  EPA has previously concluded from the neurotoxicity studies an LOAEL of 200 mg/kg/day as a Acute Dietary Point of Departure; uncertainty/FQPA safety factors of 10X UFA, 10X UFH, and 10X FQPA; an acute RfD=0.2 mg/kg/day and acute PAD= 0.2 mg.kg/day.  An LOAEL of 200 mg/kg/day is based on low arousal and decreased motor activities in males, decreased rearing in females, in addition to decreased bodyweight gain and food consumption in both sexes on Day 1.

7. Immunotoxicity:  Based on the results of 28-day immunotoxicity studies in rats and mice, EPA has previously concluded that picoxystrobin has no effects on the immune system in rats and mice. 

8. Animal metabolism: Metabolism and pharmacokinetic studies in the rats, lactating goats and laying hens were previously evaluated by EPA and demonstrate that picoxystrobin residues are rapidly absorbed, metabolized and eliminated.  There was no evidence of accumulation of residues in any tissues or organs.  The metabolic pattern was always complex and numerous metabolites were identified.  The main metabolic reactions, however, are very comparable for all tested animal species and most metabolites were present at low levels.

Absorption, distribution, metabolism and elimination of picoxystrobin and metabolites were reinvestigated in domesticated laying hens (Gallus gallus).  14C-Picoxystrobin was administered via gelatin capsules to ten laying hens as a single oral dose for 14 consecutive days.  Picoxystrobin metabolism in laying hens was extensive. Metabolites observed in the picoxystrobin hen metabolism study are consistent with the metabolites observed in previously EPA evaluated picoxystrobin animal (rat, goat and hen) metabolism studies and with classes of conjugates commonly observed in hen metabolism studies.
      
9. Metabolite toxicology: The residues of concern are the parent compound only, picoxystrobin. 
      
10. Endocrine disruption:  There is no evidence to suggest that picoxystrobin has any primary endocrine disruptive potential.  Reproductive and developmental findings provided no evidence of an enhanced sensitivity of the young.

C. Aggregate Exposure

1. Dietary Exposure Food and Water: 

Conservative acute and chronic dietary risk assessments of the registered and proposed picoxystrobin uses was performed to estimate potential picoxystrobin exposure from consumed food.  The assessments were conducted with DEEM-FCID (Dietary Exposure Evaluation Model with Food Commodity Intake Database, version 4.02) software using field trial residue levels for crops, animal feeding study values for meat, milk, and poultry food items, and an assumption of 100% crop treated with picoxystrobin. 

An acute dietary risk assessment was conducted using an acute reference dose (aRfD) of 0.2 mg/kg bw/d which was derived from the acute neurotoxicity study based on behavioral effects and decreased bodyweight gain and food consumption at the LOAEL of 200 mg/kg/day, and an uncertainty factor of 1000; the uncertainty factor includes the conventional 10X inter-species extrapolation and the 10X intra-species variation factors and a 10X uncertainty factor for the use of the LOAEL.  A conservative acute dietary risk assessment of the registered and proposed picoxystrobin uses indicated the US Population exposure at the 95[th] percentile was 13% of the acute RfD.  The sub-populations with the highest exposure were Children 1-2 years and Adults 50-99 years with 16% of the acute RfD.  These can be considered very conservative estimates of exposure. 

A chronic dietary analysis was conducted using a chronic reference dose (cRfD) of 0.046 mg/kg/day for all populations which was derived from the chronic toxicity study in the dog, based on reduced bodyweight, and an uncertainty factor of 100.  A conservative chronic dietary risk assessment of the registered and proposed picoxystrobin uses indicated the US Population exposure was 6% of the chronic RfD.  The sub-population with the highest exposure was children 1-2 years with 9% of the chronic RfD. These can be considered very conservative estimates of exposure.

Drinking Water: The existing use of picoxystrobin on corn is associated with the highest potential impacts to surface water, resulting in an acute picoxystrobin concentration of 29.6 ppb and a chronic value of 5.87 ppb.  Groundwater concentrations have been estimated to be much lower.  When the 29.6 ppb surface water value was included in the acute dietary risk assessment there was little change from the food only assessment; the predicted exposure for the US population for food and drinking water was 14% of the aRfD and 16% for the sensitive populations of children 1-2 years and adults 50-99 years.  When the chronic dietary risk assessment was conducted with food and the chronic drinking water value of 5.87 ppb, the predicted exposure for the US population was 7% of the cRfD; the most sensitive subpopulation, children 1-2 years, had an estimated exposure of 9% of the cRfD.  

2. Non-Dietary Exposure: The proposed uses of picoxystrobin do not include any sites that would result in residential exposure.  Therefore, the aggregate risk is the sum of the risk from food and water.

D. Cumulative Effects

Section 408(b)(2)(D)(v) of the FFDCA requires that, when considering whether to establish, modify, or revoke a tolerance, the Agency consider ``available information'' concerning the cumulative effects of a particular pesticide's residues and ``other substances that have a common mechanism of toxicity.'' Picoxystrobin is a foliar fungicide which belongs to the class of strobilurin chemistry, and picoxystrobin is a novel strobilurin analog.  EPA has not made a common mechanism of toxicity finding as to picoxystrobin and any other substances, and picoxystrobin does not appear to produce a toxic metabolite produced by other substances.

E. Safety Determination

1. US Population: Based on the completeness and reliability of the toxicity data, and using conservative exposure assumptions it is concluded that dietary exposure (food and water) from the proposed and registered uses of picoxystrobin are far below the EPA levels of concern of 100% of the RfD. In addition, all handler exposure scenarios also have MOE greater than 100. Therefore, there is a reasonable certainty that no harm will occur to the US Population from aggregate exposure to picoxystrobin.

2. Infants and Children: In assessing the potential for additional sensitivity of infants and children to residues of picoxystrobin, data from developmental and multigeneration reproductive toxicity studies were considered.  Developmental studies are designed to evaluate adverse effects on the developing organism resulting from pesticide exposure during pre-natal development. Reproduction studies provide information relating to reproductive and other effects on adults and offspring from pre-natal and post-natal exposures to the pesticide. The studies with picoxystrobin demonstrated no evidence of developmental toxicity at exposures below those causing maternal toxicity. This indicates that developing animals are not more sensitive to the effects of picoxystrobin administration than adults.  Consideration of the toxicology database for picoxystrobin leads to no additional concerns for infants and children.  Therefore, the FQPA safety factor can be established at 1X.  Using conservative exposure assumptions, the margins of exposure that will result for short- and intermediate-term aggregate exposure (food plus water) to residues of picoxystrobin are much greater than 100 for children. This value is based on a worst-case aggregate exposure calculation of a child 1-2 who has a background dietary exposure to potential residues.  Therefore, there is a reasonable certainty that no harm will occur to infants and children from aggregate exposure to residues of picoxystrobin.

F. International Tolerances

Picoxystrobin is registered and tolerances are established in a number of countries.  There are no Codex Alimentarius Commission (CODEX) maximum residue levels (MRLs) established for residues of picoxystrobin.