Adverse Effects:

Adverse Effects:
Ataxia
Bladder
Blood
Body Weight Decrease
Bone (including Cleft Palate)
Cancer: Possible Human Carcinogen - BREAST, BLADDER, KIDNEY
Cholesterol
Clastogenic /Mutgenic
Developmental toxicant
Endocrine: Breast
Endocrine: Ovary
Kidney
Liver
Teratogen
Environmental

Environmental Effects:

Persists in soil

Highly to very highly toxic to rainbow trout and bluegill sunfish.

Highly toxic to marine/estuarine fish, mollusks, and shrimp on an acute basis

Endangered species levels of concern are exceeded for freshwater organisms and estuarine/marine invertebrates

Dow AgroSciences & IR-4. Pesticide Tolerance Petition. Petitions: PP 1E6326, PP 2E6360 and PP 2E6466 for the raw agricultural commodities:

• The summary of the petition was prepared by Interregional Research Project Number 4 (IR-4). IR-4 submitted the petitions on behalf of the registrant, Dow AgroSciences LLC, who prepared this notice of filing.
• Genotoxicty. Ethalfluralin was weakly mutagenic in activated strains TA1535 and TA100 of salmonella typhimurium, but not in strains TA1537, TA1538, and TA98 in an Ames assay... In Chinese hamster ovary cells, ethalfluralin was negative without S9 activation, but it was clastogenic with activation.
• Reproductive and developmental toxicity. The developmental NOAEL in rats was 1,000 mg/kg/day, the highest dose. In rabbits the NOAELs for maternal and developmental toxicity were 75 mg/kg/day. The maternal LOAEL at 150 mg/kg/day was based on abortions and decreased food consumption. These effects as well as decreased weight gain, enlarged liver, and orange urine were found at 300 mg/kg/day. In this study developmental toxicity was observed. The developmental LOAEL in rabbits was 150 mg/kg/day, based on slightly increased resorptions, abnormal cranial development, and increased sternal variants. In a three-generation rat reproduction study, the parental NOAEL was 12.5 mg/kg/day. The parental LOAEL was 37.5 mg/kg/day, based on depressed mean body weight gains in males in all generations. No treatment-related effects were noted on reproductive parameters and the NOAEL was 37.5 mg/kg/day or greater. A 7-month multigeneration bridging study was conducted with doses equivalent to 0, 8, 20, or 61 mg/kg/day in the
diet of Fischer 344 rats. The parental NOAEL was 20 mg/kg/day. The parental LOAEL was 61 mg/kg/day based on increased liver weights.
• Chronic toxicity. Ethalfluralin was administered to Fisher 344 rats in the diet for 2 years in combined chronic toxicity and carcinogenicity replicate studies. The doses were equivalent to 0, 4.2, 10.7, or 32.3 mg/kg/day. The NOAEL for systemic effects was 32.3 mg/kg/day. Mammary gland fibroadenomas were found in dosed female rats at statistically significant incidences in the mid and high doses. EPA's Office of Pesticide Program's Carcinogenicity Peer Review Committee concluded that, ethalfluralin should be classified as Group C, a possible human carcinogen, based on increased mammary gland fibroadenomas and adenomas/fibroadenomas combined in female rats. The tumor incidences were statistically significant at both the mid and high dose, and exceeded the upper range of historical controls. Based on a low dose extrapolation, the Q1* of 8.9 x 10-2 (mg/kg/day)-1 has been calculated. Based on both registered and proposed product uses, exposure to ethalfluralin from food is estimated to not exceed a lifetime cancer risk of 8.47 x 10-7. Cancer risks of less than 1 x 10-6 are generally considered to be negligible.
• Beagle dogs were given 0, 4, 20, or 80 mg/kg/day orally, by capsule, for 1 year. The NOAEL was 4 mg/kg/day. The LOAEL was 20 mg/kg/day, based on increased urinary bilirubin, variations in erythrocyte morphology, increased thrombocyte count, and increased erythroid series of the bone marrow. Elevated alkaline phosphatase levels were found at the two higher doses and siderosis of the liver at the high dose.