CHRONIC TOXICITY ONCOGENICITY OF DIMETHYLACETAMIDE IN RATS AND MICE FOLLOWING INHALATION EXPOSURE

The potential chronic toxicity and oncogenicity of dimethylacetamide ( DMAC) was evaluated by exposing male and female rats and mice to 0, 25 , 100, or 350 ppm DMAC for 6 hr/day, 5 days/week for 18 months (mice) or 2 years (rats). Clinical pathology was evaluated at 3, 6, 12, 18, a nd 24 (rats only) months. An interim euthanization for rats occurred a t 12 months and hepatic cell proliferation in rats and mice was examin ed at 2 weeks and 3 and 12 months. No compound-related effects on surv ival were observed. Rats exposed to 350 ppm had lower body weight and/ or body weight gain. There were no compound-related effects on body we ight or weight gain in mice at any concentration. There were no compou nd-related adverse effects on the incidence of clinical signs of toxic ity in rats or mice. No hematologic changes were observed in either sp ecies. Serum sorbitol dehydrogenase activity was increased in rats exp osed to 350 ppm. Serum cholesterol and glucose concentrations were sig nificantly higher in 100 and 350 ppm female rats. Compound-related mor phological changes were observed in the liver. In rats, exposure to 10 0 or 350 ppm produced increased absolute and/or relative liver weights , hepatic focal cystic degeneration, hepatic peliosis, biliary hyperpl asia (350 ppm only), and lipofuscin/hemosiderin accumulation in Kupffe r cells. In mice, exposure to 100 or 350 ppm produced increased absolu te and relative liver weights (350 ppm females only), accumulation of lipofuscin/hemosiderin in Kupffer cells, and centrilobular single cell necrosis. Male rats exposed to 350 ppm also had significantly higher absolute and relative kidney weights which correlated with the gross a nd microscopic changes resulting from a compound-related increase in s everity of chronic progressive nephropathy. Female mice exposed to 350 ppm had an increased incidence of bilateral, diffuse retinal atrophy. No increase in hepatic cell proliferation was seen in mice or rats at any exposure concentration. DMAC was not oncogenic under these experi mental conditions in either the rat or mouse. The NOAEL for male and f emale rats and mice is 25 ppm. (C) 1995 Society of Toxicology