Toxicity studies of acetone administered in the drinking water of rodents

Two- and thirteen-week toxicity studies were conducted using male and female F344/N rats and B6C3F1 mice. Animals were exposed to the following concentrations of acetone in their drinking water: two-week studies 0; 5000; 10,000; 20,000; 50,000; or 100,000 ppm acetone. Thirteen-week rat and female mouse studies 0; 2500; 5000; 10,000; 20,000; or 50,000 ppm acetone. Thirteen week male mice were exposed to 0; 1250; 2500; 5000; 10,000; or 20,000 ppm acetone. Depressed body weight gain was restricted to the 50,000 and 100,000 ppm exposure groups. Male and female mice exposed respectively to 20,000 or 50,000 ppm acetone for 2 weeks developed hepatocellular hypertrophy. This change was not apparent after 13 weeks of exposure although relative and absolute liver weight was increased in high dose female mice. Bone marrow hypoplasia was observed in 5/5 high dose (100,000 ppm) male rats during the 2-week studies. Treatment of male rats for 13 weeks resulted in a variety of mild and subtle hematological changes that often occurred at relatively low levels of exposure (5000 ppm) and resembled those seen during the clinical condition of megaloblastic anemia. Changes characteristic of hypogonadism (depressed sperm motility and cauda epididymal and epididymal weight and elevated incidence of abnormal sperm) were observed in male rats receiving 50,000 ppm acetone for 13 weeks. The incidence and severity of a kidney lesion that is morphologically similar to the spontaneously occurring nephropathy among aging F-344 rats were increased at 20,000 and 50,000 ppm acetone, respectively, in 13-week male rats. In summary, the effects of acetone were either subtle in nature or occurred during very high levels of exposure confirming acetone's low level of toxicity. The daily levels of acetone exposure were often several-fold greater than possibly encountered by humans during the accidental consumption of contaminated groundwater (250 ppm; 5 mg/day) and frequently exceeded maximum levels reported following acute toxic exposures (2,500 mg/kg).