SUBCHRONIC ORAL TOXICITY STUDY OF DIISOPROPYL METHYLPHOSPHONATE IN MINK

Diisopropyl methylphosphonate (DIMP), produced during manufacture of t he chemical agent GB (Sarin), is a groundwater contaminant at Rocky Mo untain Arsenal, Colorado. DIMP was fed for 90 days to dark brown ''Ran ch Wild'' mink housed under controlled indoor conditions. One-year-old mink, 10 of each sex, were fed 0, 50, 450, 2700, 5400, or 8000 ppm in standard ranch diet. Actual DIMP consumption was 0, 8, 73, 400, 827, and 1136 mg/kg body wt/day, respectively. Two additional groups of 10 served as ''pair-fed'' controls. Body weight and food intake were reco rded weekly. Complete blood count and 15 chemical analytes were measur ed at Weeks 0, 3, 7, and 13. Necropsy and microscopic examination were performed on all mink. No clinical morbidity or deaths occurred. Both sexes fed 8000 ppm ate approximately 20% less and weighed approximate ly 20% less than the controls; 5400 ppm females had a 10% weight decre ment. Plasma cholinesterase (ChE) decreased in the top three dose grou ps starting at Week 3. At 13 weeks, decrements were approximately 50% but returned to normal after 1 week without DIMP. Erythrocyte ChE was not reduced. Heinz bodies occurred in 10-15% of RBCs in 50% of 8000 pp m mink at 13 weeks, and 0.1-2.0% of RBCs in 25% at 2700 ppm. There wer e mild decreases in RBC count, hematocrit, and hemoglobin, and increas es in reticulocyte count, at the 5400 and 8000 ppm doses. All recovere d within 3 weeks after DIMP was withdrawn. The 8000 ppm group had marg inal splenic hematopoiesis, histologically. No other treatment-related changes were noted. The 450 ppm dose was a clear no-effect level (app roximately 73 mg DIMP/kg body wt/day). Compared to reports of similar studies of DIMP in rats and dogs, these mink displayed no unique speci es susceptibility. (C) 1994 Society of Toxicology.