The comparative metabolism of diisopropyl methylphosphonate in mink and rats.

This study reports the metabolism of carbon-14labeled diisopropyl methylphosphonate (DIMP) in mink and rats, undertaken to better understand the dose-related mortality reported for mink in a previous study. In both male and female mink and rats, DIMP was rapidly absorbed after oral administration; it was metabolized by a saturable pathway to a single metabolite, isopropyl methylphosphonate (IMPA), which was rapidly excreted, primarily in the urine (90%). Fecal radioactivity, also identified as IMPA, was 1.7-3.1% of the administered dose. Female rats had a slower rate of conversion of DIMP to IMPA and less total excretion of IMPA than male rats. Metabolism of DIMP administered intravenously was not very different from that given orally in both species. These data indicate that mink absorb, metabolize, and excrete DIMP (as IMPA) in a manner very similar to mice, rats, and dogs.

Hematologic and serum chemistry reference values for adult brown mink.

Hematologic and serum chemistry reference values were determined for 160 12-month-old brown untamed captive mink (Mustela vision). Blood was obtained by jugular venipuncture after administration of ketamine and xylazine. There were no statistically significant differences between male and female mink. The packed cell volume, hemoglobin, and red blood cell count were 10 to 20% lower than previously reported for non-anesthesized mink. Serum glucose, alanine aminotransferase and aspartate aminotransferase values also were lower than previously reported values.

Hematologic response of adult brown mink to oxidative stress.

We evaluated the response of mink to oral administration of the oxidant compound propylene glycol (PG) to better understand the relative susceptibility of mink red blood cells (RBC) to oxidant injury. Feeding a diet containing 12% PG to 6 mink for 1 w resulted in a 17% decrease in hematocrit, a 21% decrease in RBC count and a 4.8-fold increase in reticulocyte count. A marked increase in Heinz body and eccentrocyte numbers was consistent with oxidative injury to RBC. Because of high food intake, mink ingested approximately twice the quantity of PG/kg body weight compared to domestic cats fed diets containing 12% PG. Therefore, the severity of the hematologic dyscrasia in mink may be the result of greater intake of PG rather than unique sensitivity of mink RBC of oxidative injury. However, the high food intake and the mink's position at the top of the food chain may increase its exposure to environmental contaminants.

Subchronic oral toxicity study of diisopropyl methylphosphonate in mink.

Diisopropyl methylphosphonate (DIMP), produced during manufacture of the chemical agent GB (Sarin), is a groundwater contaminant at Rocky Mountain Arsenal, Colorado. DIMP was fed for 90 days to dark brown "Ranch 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 recorded weekly. Complete blood count and 15 chemical analytes were measured 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 approximately 20% less than the controls; 5400 ppm females had a 10% weight decrement. Plasma cholinesterase (ChE) decreased in the top three dose groups 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 ppm mink at 13 weeks, and 0.1-2.0% of RBCs in 25% at 2700 ppm. There were mild decreases in RBC count, hematocrit, and hemoglobin, and increases in reticulocyte count, at the 5400 and 8000 ppm doses. All recovered within 3 weeks after DIMP was withdrawn. The 8000 ppm group had marginal splenic hematopoiesis, histologically. No other treatment-related changes were noted. The 450 ppm dose was a clear no-effect level (approximately 73 mg DIMP/kg body wt/day). Compared to reports of similar studies of DIMP in rats and dogs, these mink displayed no unique species susceptibility.

Nonsuppurative meningoencephalomyelitis of unknown etiology in mink.

A central nervous system disease of mink occurred in three unrelated fur farms in Oregon in September, 1981. Only kits four to five months old were affected. Clinical signs consisted of posterior ataxia progressing to complete posterior paralysis with loss of motor control and sensation. Complete or partial recovery occurred in approximately 1.5 months in most mink. Microscopic lesions consisted of severe nonsuppurative meningoencephalitis and meningomyelitis with vacuolation of the white matter of the brain and spinal cord. Canine distemper virus infection and other recognized causes were ruled out on the basis of clinical signs, history, lesions, or laboratory findings. Experimental inoculations of mink with brain and spinal cord specimens from affected mink failed to reproduce the disease.