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**EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER**  **EPA Registration Division contact: Shaja Joyner**  **(703)30 8**  **- 3194**  Company Name: Taminco US In c. OPP Petition No.: **4E8243** EPA has received a pesticide petition **4E8243** from Taminco US In c., 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 amending a time

- limited import tolerance for residues of thiram in or on the raw agricultural commodity banana at 0.8 parts per million (ppm)
. EPA has determined that the petition contains data or information regarding the elem ents 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. The time

- limited import tolerance for residues of thiram in or on banana will expire on March 31, 2014. The time

- limited tolerance is proposed for exten sion to March 31, 2015. Additional data may be needed before EPA rules on the petition. 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. Banana s amples were analyzed according to Anal yt ical Method# Meth

- 100, Revision #4, "Determination of Thiram in Raw Agricultural Commodities, Processed Commo dities and Other Plant Material. " D etection and quantitation for thiram (as CS 2 ) were conducted using gas chromatograph y (GC) employing sulfur

specific flame photometric detection (FPD). T he limit of quantitation (LOQ) was 0.05 ppm. 3. Magnitude of residues. Banana residue trials were conducted in 5 countries that represent the major banana growing countries that export bananas to the United States. Formulations containing either 42% thiram or 60% thiram were applied at a rate of 1.12 pounds thiram per acre. Application began when the fruit had completel y emerged from the flower, were trimmed and bagged. The applications continued on a five to seven day basis until immediately

prior to harvest maturit y for a total of 1 0 applications. The LOQ for the analy

tical method was 0.05 ppm
. Based on anal yt ical results, the Agency establish ed a time

- limited import tolerance for thiram in or on bananas of 0.8 ppm
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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 and 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 subsequent ly evaluated in functional observational batteries (FOB) and motor function observations. Neuropathological evaluations were performed. The Lowest Observed Adverse Effect Level (LOAEL) wa s 150 mg/kg based on FOB effects (lethargy , lower temperature, redu ced 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 weight gains and clinical signs of toxicity . The developmental NOAEL was 7.5 m g/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 studies, 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 study 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. 4. Subchronic Toxicity Thiram was administered via the diet to rats for 13 weeks. The LOEL was 2 50 ppm3

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 th iram 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 hematology 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 D ietary exposure is expected from this petition as residues of thiram are found in whole bananas. ii. Drinking water No additional water exposure is expected
. 1. Non
- dietary

exposure N/A

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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 c hemical compounds. E. Safet y Determination 1. U.S. Population The acute dietary

exposure for the General U.S. Population was 34.20 % 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 was estimated to be 0.0 13639 mg/kg/day , equivalent to 85.88 % of the A RfD
. Chronic dietary

exposure for the General U.S. Population was 4.3 % of the CRfD
. 2. In fants and Children Th e acute dietary

exposure for Infants and Children r anged from 48.2% to 103.29% 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 5.4 % to 14.3 % of the CRfD with the highest chronic dietary exposure for Children 1

- 6 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).