1

**EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER**  **EPA Registration Division contact: Shaja Joyner**  **(703)308**
**- 3194**  Company Name: Taminco US In c. , OPP Petition No.: 4E8250 EPA has received a pesticide petition 4E8250 from Taminco US Inc., Two Windsor P laza, Suite 411, 7540 Windsor Drive, Allentown, PA 18195 pursuant to section 408(d) of the Federal Food, Drug and Co smetic Act (FFDCA) 21 U.S.C. 346a(d), to amend 40 CFR part 180. By establishing an import tolerance for residues of thiram in or on the raw agricultural commodity

avocado at 8 parts per million (ppm) for avocado whole fruit, EPA has determined that the petition contains data or information regarding the elements set forth in section 408 (d)(2) of FDDCA; however, EPA has not full y evaluated the sufficiency of the submitted data at this time whether the data supports granting of the petition. Additional d ata 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. Avocado samples were analy zed according to ALS Laboratory 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 conduc ted using 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. Three residue trials on avocado, HAAS variet y, were conducted in the State of Michoacan, Mexico (NAFTA Region 18). This area is representative of the avocado production area in Mexico from which avocadoes may be imported to the United States. A formulation containing 80% w/w thiram was applie d at a rate of 2.4 kg a.i./hectare equivalent to 2.14 lb a.i/acre. The avocados were treated on 14 ± 1 day s preharvest (PHI), 7 ± 1 day s PHI and on the day of harvest (0 day

PHI ). Analy tical results support the establishment of import tolerance of 8 ppm f or whole avocado fruit. A tolerance for avocado pulp has not been proposed as no thiram residues were found in avocado pulp samples.2

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 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 weight 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 NOE L 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 neurotoxi city 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 was 250 ppm based on effects on bod y 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 incidenc es of hyperactivit 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 w as 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 metabolites 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 stu dies conducted with thiram. C. Aggregate 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 e xposure is expected as this is an import tolerance petition.4

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 was 23.3 % of the AR fD. The population group with the high est acute dietary exposure was Females 13

- 49 y rs. Total acute exposure for females 13

- 49 y ears was estimated to be 0.0 09522 mg/kg/day , equivalent to 68.0 % of the A RfD

. Chronic dietary

exposure for the General U.S. Population and the multiple population subgroups was 3 .2% of the CRfD

. 2. In fants and Children Th e acute dietary

exposure for Infants and Children ranged from 27.4% to 50% of the ARfD. The highest acute diet ary exposure for Infants and Children was Children 1

- 2 ye ars. Chronic dietary

exposure for Infants and Children ranged from 4.2% to 9.2% of the CRfD with the highest chronic dietary exposure for Children 1

- 6 y ears. 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 (C odex, February 2006) for thiram are apples (5 ppm), bananas (2 ppm), stone fruits ( 7 ppm) and strawberries (5 ppm).