Chronic Toxicity, Reproductive, and Teratogenic Studies with Oxamyl

Chronic Toxicity, Reproductive, and Teratogenic Studies withOxamyl. KENNEDY, G. L., JR., (1986). Fundam. Appl Toxicol. 7,106-118. Oxamyl (methy1N',N'-dimethy1-N'-[(methylcarba-moyl)oxy]-l-thiooxamimidate;CAS 23135-22-0) was tested for oral toxicity in the rat anddog (90-day and 2-year feeding studies) and in the mouse (2-yearfeeding study). Teratogenic potential was evaluated in the ratand rabbit and functional reproductive capacity was studiedin the rat in a one- and a three-generation reproduction study.Rats fed a diet containing oxamyl at 500 ppm showed clinicalsigns of cholinesterase inhibition and body weight loss within2 days. Feeding of either 100 or 150 ppm oxamyl for 90 daysproduced a reduced rate of weight gain without other signs ofresponse, and no effects were detected at 50 ppm. An oxamylfeeding period of 2 years also showed depressed body weightgains in rats fed either 100 or 150 ppm. Cholinesterase activitywas depressed only during the first week of feeding and onlyin the 150-ppm group. All other indices of response, includingthe type and distribution of tumors, were similar in the testand control rats and it was concluded that the no-observed-effectlevel was 50 ppm (equivalent to approximately 5 mg/kg). Micefed oxamyl at 100 ppm for 6 weeks showed signs of cholinesteraseinhibition and some mortalities, so the dietary concentrationwas reduced to 75 ppm in the 2-year study. Body weights of micefed oxamyl at 50 or 75 ppm were lower than controls during thefirst 6 months of the study. No other signs of a toxic responseto oxamyl were seen in mice and a no-observed-effect level of25 ppm (approximately 2.5 mg/kg) was assigned to this compound.No evidence of a tumorigenic response was obtained. Dogs fedoxamyl at 150 ppm for 2 years showed marginal increases in serumalkaline phosphatase activity and cholesterol concentrationbut no tissue pathology was seen. No evidence of cholinesteraseinhibition was seen. It was concluded that the no-observed-effectlevel for oxamyl in the dog was 100 ppm (approximately 2.5 mg/kg).In the one- and three-generation reproduction studies, littersizes were somewhat lower in rats fed oxamyl at 100 or 150 ppmoxamyl with normal values seen at 50 ppm. Weanling body weightswere normal in rats in the 50-ppm group for three generationsbut were reduced in the one-generation study. Pup body weightswere lower in rats in both the 100- or 150-ppm groups. Transferof F3b pups, derived from dams in the 150-ppm group, to controldiets following delivery improved the weight gains. No evidenceof a teratogenic response was seen in the rat although a reducedrate of weight gain was seen in pregnant rats fed oxamyl at100 ppm or greater. In the rabbit, no evidence of a teratogenicresponse was found even at dose levels in which maternal toxicitywas encountered.