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**EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER**  **EPA Registration Division contact: Shaunta**  **Hill ( 703)**  **3 47**  **- 8961**  Company Name: Taminco, Inc. OPP Petition No.: 2F8106 EPA has received a pesticide petition 2F8106 from Taminco, Inc., Two Windsor Plaza, Suite 411, Allentown, PA 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 b y establishing a tolerance for residues of thiram in or on the raw agricultural commodity strawberry at 20 parts per million (ppm) for strawberry whole fruit, EPA has determined that the petition contains data or information regardi ng the elements set forth in section 408 (d)(2) of FDDCA; however, EPA has not fully evaluated the sufficiency of the submitted data at this time whether the data supports granting of the petition. Additional data may be needed before EPA rules on the pet ition. A. Residue Chemistry 1. Plant metabolism. The metabolism and chemical nature of residues of thiram in plants has been extensivel y evaluated and is adequatel y understood. 2. Analy tical method. Strawberry samples were analyzed according to ALS L aboratory Group method MS 133.02 "The Determination of Mancozeb and/or other Ethylene

- bis

dithiocarbamates (EBDCs) as CS 2 in Plant Tissue by GC/MS". Detection and quantitation for thiram (as CS 2 ) were conducted usi ng a gas chromatograph (GC) equipped with a mass spectral detector for determination of CS 2 . The limit of quantitation (LOQ) was 0.05 ppm reported as carbon disulfide (CS 2 ) evolved. 3. Magnitude of residues. Ten field trials were conducted on strawberries in New York (EPA region I), North Carolina (EPA region II), Florida (EPA region III), Minnesota (EPA region V), California (EPA region X) and Oregon (EPA region XII). These locations are representative of the s trawberry production areas in the United States. A formulation containing 44% w/w thiram was applied at a rate of 2.6 lb a.i./acre. The strawberries were treated on 41±2 day s preharvest (PHI), 31±2 day s PHI, 21±2 day s PHI, 11±2 day s PHI and 1 day PHI . In addition, 4 trials were previousl y conducted with a thiram formulation containing 75% w/w thiram at a rate of 3.3 lb. a.i./acre. Taminco has applied to reduce the application rate for this product on strawberry to 2.6 lb a.i./acre. Analy tical results fr om the 1 day PHI from those were included in the analyses using proportional change to the values. Anal yt ical results support the establishment of tolerance of 20 ppm for whole strawberries

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B. Toxicology

Profile 1. Acute toxicity . The acute oral LD50 was 26 00 mg/kg (Toxicity Category III). The acute dermal LD50 was greater than 2000 mg/kg (Toxicity Category I II)

. The acute inhal ation LC50 for was ≥ 3.46 mg/L (Toxicity Category III). Thiram is a moderate ey e irritant, a very slight dermal irritant an d a moderate skin sensitizer. In an acute neurotoxicity

study , Sprague

- Dawley

rats were orall y gavaged at 0, 5, 150, and 600 mg/kg, and were subsequently evaluated in functional observational batteries (FOB) and motor function observations. Neuropathological evaluations were performed. Th e Lowest Observed Adverse Effect Level (LOAEL) wa s 150 mg/kg based on FOB effects (lethargy , lower temperature, reduced startle response, no tail pinch response), reduced motor activity , and reduced brain weights

. The N o O bservable Adverse Effect Level (NO AEL ) for neuro toxicity was 5 mg/kg. 2. Genotoxicity

. Genotoxicity

evaluations of thiram were negative in a mammalian cell gene mutation assay with Chinese Hamster V9 cells, a chromosomal aberrations assay in Chinese hamster ovary

cells, an DNA repair study in cultured rat hepatocy tes and an in vivo micronucleus study

in mice. 3. Reproductive and Developmental Toxicity In a developmental toxicity study in rats, a maternal NOAEL was not achieved. The maternal LOAE L was 7.5 mg/kg/day based on reduced body we ight gains and clinical signs of toxicity . The developmental NOAEL was 7.5 mg/kg/day

. Pregnant female rabbits were dosed with thiram via gavage on gestation days 7 to 19. The NOEL for maternal and developmental toxicity was 10 mg/kg/day , the highest tested dose. Two multigeneration studies with thiram were conducted in rats. In both stu dies, the rates were exposed over two generations. In the first study , the parental NOELwas 25 ppm, the reproductive NOELwas 50 ppm and the fetal NOEL was 50 ppm. The results from the second stud y showed a parental NOEL was 20 ppm, the reproductive NOEL was >180 ppm and the fetal NOEL was 20 ppm. A developmental neurotoxicity study was conducted in which female rats received diets containing 0, 20, 45 or 90 ppm thiram from gestation day 3 through postnatal day

20. The maternal sy stemic and neurotoxicity L OAEL was 90 ppm based on decreased body weight, bod y weight gain and food consumption, c linical signs of toxicity and F B findings. The maternal NOAEL was 45 ppm . The offspring s ys temic and neurotoxicity LOAEL was 45 ppm based on increased locomotor activity in females on PND 17. The offspring NOAEL was 20 ppm.3

4. Subchronic Toxicity Thiram was administered via the diet to rats for 13 weeks. The LOEL wa s 250 ppm based on effects on body weight, bod y weight gain, food consumption, hematologic and clinical chemistry

parameters, organ weights and liver histopathologic findings. The NOEL was 50 ppm. In a subchronic neurotoxicity study , rats were exposed to thiram technical (98.76% a.i.) in their diet at doses of 0, 30, 125, or 500 ppm. The neur otoxicity L OAEL is 125 ppm , based on increased numbers of rearing events and elevated incidences of h yperactivit y in females at weeks 8 and 13. The NOAEL was 30 ppm for femal es and 125 ppm for males. 5. Chronic Toxicity In a combined chronic/oncogenicit y study, Thiram technical was administered to albino rats in the diet for 104 weeks. The LOAEL was 119 ppm b ased on a reduction in body weight gain, changes in hematolo gy and clinical chemistry parameters , and an increased incidence of bile duct h yperplasia . The NOAEL was 16.3 ppm
. Thiram was administered to male and female beagle dogs via the diet for 52 weeks. T he LOAEL was 90 ppm (2.6 mg/kg/day) based on elevated cholesterol levels and increases in liver

- to
- body

weight ratio. T he NOAEL was 30 ppm (0.84 mg/kg/day). 6. Animal Metabolism Thiram is readil y absorbed (via the oral route), distributed, extensively metabolized and eliminated primarily

in the expired air and urine of rats within 24 hours following single or repeated oral administrations. No sex differences in metabolism were noted and very low levels were found in tissues (1.5

- 4.2%). 7. Metabolite Toxicity No metabol ites of toxicologic concern have been noted. 8. Endocrine Disruption No indication of potential endocrine effects have been seen in any of the toxicological studies including reproductive and developmental toxicity studies conducted with thiram. C. Aggre gate Exposure 1. Dietary

exposure i. Food

. No additional dietary

exposure is expected from this petition as no residues of thiram are found in the edible avocado pulp. ii. Drinking water No additional water exposure is expected

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1. Non
- dietary

exposure N/A

- Remove D. Cumulative Effects The USEPA is developing methodologies for assessing cumulative risks for chemicals having common mechanism s of toxicity

. No available data indicate that the toxic effects produced b y thiram would be cumulative with those of an y other chemical compounds. E. Safet y Determination 1. U.S. Population The acute dietary

exposure for the General U.S. Population ranged from 32.02% to 3 3.78% of the ARfD. The population group with the high est acute dietary exposure was Children 1

- 2 years . Total acute exposure for females 13

- 49 years ranged from 0.0 1 1442 mg/kg/day to 0.012454 mg/kg/day , equivalent to 8 1.73 % and 88.96% of the A RfD , respectivel y . Chronic dietary

exposure for the General U.S. Popul ation was 4. 1 % of the CRfD

. 2. In fants and Children Th e acute dietary

exposure for Infants and Children ranged from 4 0.8 % to 10 1.7 % of the ARfD. The highest acute dietary exposure for Infants and Children was Children 1

- 2 ye ars. Chronic dietary

exposure for Infants and Children ranged from 5. 1 % to 1 8
. 5 % of the CRfD with the highest chronic dietary exposure for Children 1

- 2 years. F. International Tolerances Codex MRL S have been established for the Dithiocarbamates as the sum of residues of zineb, ziram, thiram, nickel bis(dimethyl dithiocarbamate), ferbam, propineb, polycarbamate, mancozeb, maneb and metiram which are calculated as carbon disulfide. Applicable MRL s (Codex, February 2006) for thiram are apples (5 ppm), bananas(2 ppm), stone fruits ( 7 ppm) and strawberries (5 ppm).