Document ByZQVb83dD2onV2b511QMjaRk

P-1 A ZZZ Q jm DuPont Haskell Global Centers for Health and Environmental Sciences ( f 1090 Elkton Road, P.O. Box 50 . i UD Newark, DE 19714-0050 8EHQ-92-2267 May 13,2008 ' C" U Via Federal Express Document Processing Center (Mail Code 7407M) Room 6428 Attention: 8(e) Coordinator Office of Pollution Prevention and Toxics U.S. Environmental Protection Agency 1201 Constitution Ave., NW Washington, DC 20004 Dear 8(e) Coordinator: f V0P00 8EHQ-92-2267 This letter is to inform you of the results of two 28-day feeding studies in rats with the R&D test substance referenced above. The studies were conducted to evaluate the technical competency of the laboratories, one in Asia and one in Eastern Europe. Groups of male and female rats were fed diets containing the test substance at concentrations of 0, 250, 1250 or 2500 ppm for approximately 28 days. Due to poor condition, the 2500 ppm group at one laboratory was fed control diets on some test days. The studies included evaluations for body weight and nutritional parameters, clinical and ophthalmological signs, clinical pathology, and anatomic pathology. The studies also included evaluations of neurobehavioral parameters and motor activity (one laboratory). Exposure to 1250 ppm and above was associated with reductions in body weight, body weight gain, food consumption, and food efficiency, clinical pathology evidence of regenerative anemia, and clinical and anatomic pathology effects secondary to anemia (pallor, hunched posture, enlarged spleen, splenic and extramedullary hematopoiesis), liver hyperplasia, epididymal sperm granulomas (one laboratory). Other clinical pathology effects observed at 1250 ppm and above included increased WBC, platelets, bilirubin, cholesterol, reduced serum protein, variable electrolyte changes, discolored urine, urobilinogen. Effects observed at 2500 ppm included increased liver enzymes (ALT, AST, GGT), increased BUN, focal and/or centrilobular liver necrosis, nephrosis, and pancreatic apoptosis. No test substance-related effects on ophthalmology or neurobehavioral parameters were observed. The NOAELs in the studies were 250 ppm (males and females). Effects were qualitatively similar among labs, with some differences in the NOAEL for individual parameters. CONTAINS NO CBI "3I I L b O P-2 This information is submitted in accordance with current guidance issued by EPA indicating EPA's interpretation of Section 8(e) of the Toxic Substances Control Act or, where it is not clear that reporting criteria have been met, it is submitted as a precautionary measure and because it is information in which EPA may have an interest. Sincerely, A. Michael Kaplan, Ph.D. Director - Regulatory Affairs AMK/SAM: cip (302) 366-5260