Chronic toxicity, reproductive, and teratogenic studies with oxamyl.
Oxamyl (methylN',N'-dimethyl-N-[(methylcarbamoyl)oxy]-1-thiooxam imidate; CAS 23135-22-0) was tested for oral toxicity in the rat and dog (90-day and 2-year feeding studies) and in the mouse (2-year feeding study). Teratogenic potential was evaluated in the rat and rabbit and functional reproductive capacity was studied in the rat in a one- and a three-generation reproduction study. Rats fed a diet containing oxamyl at 500 ppm showed clinical signs of cholinesterase inhibition and body weight loss within 2 days. Feeding of either 100 or 150 ppm oxamyl for 90 days produced a reduced rate of weight gain without other signs of response, and no effects were detected at 50 ppm. An oxamyl feeding period of 2 years also showed depressed body weight gains in rats fed either 100 or 150 ppm. Cholinesterase activity was depressed only during the first week of feeding and only in the 150-ppm group. All other indices of response, including the type and distribution of tumors, were similar in the test and control rats and it was concluded that the no-observed-effect level was 50 ppm (equivalent to approximately 5 mg/kg). Mice fed oxamyl at 100 ppm for 6 weeks showed signs of cholinesterase inhibition and some mortalities, so the dietary concentration was reduced to 75 ppm in the 2-year study. Body weights of mice fed oxamyl at 50 or 75 ppm were lower than controls during the first 6 months of the study. No other signs of a toxic response to oxamyl were seen in mice and a no-observed-effect level of 25 ppm (approximately 2.5 mg/kg) was assigned to this compound. No evidence of a tumorigenic response was obtained. Dogs fed oxamyl at 150 ppm for 2 years showed marginal increases in serum alkaline phosphatase activity and cholesterol concentration but no tissue pathology was seen. No evidence of cholinesterase inhibition was seen. It was concluded that the no-observed-effect level for oxamyl in the dog was 100 ppm (approximately 2.5 mg/kg). In the one- and three-generation reproduction studies, litter sizes were somewhat lower in rats fed oxamyl at 100 or 150 ppm oxamyl with normal values seen at 50 ppm. Weanling body weights were normal in rats in the 50-ppm group for three generations but were reduced in the one-generation study. Pup body weights were lower in rats in both the 100- or 150-ppm groups.(ABSTRACT TRUNCATED AT 400 WORDS)
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002219:Carbamates / Q000633:toxicity*; D002800:Cholinesterase Inhibitors; D004285:Dogs; D005260:Female; D008297:Male; D051379:Mice; D011247:Pregnancy; D011817:Rabbits; D051381:Rats; D012098:Reproduction / Q000187:drug effects*; D013045:Species Specificity; D013723:Teratogens; D013997:Time Factors
D002219:Carbamates; D002800:Cholinesterase Inhibitors; D013723:Teratogens; C011960:oxamyl