Toxicity Sudies of Acetone Administered in the Drinking Water of Rodents

Toxicity Studies of Acetone Administered in the Drinking Waterof Rodents. DIETZ, D. D., LEININGER, J. R., RAUCKMAN, E. J.,THOMPSON, M. B., CHAPIN, R. E., MORRISSEY, R. L., AND LEVINE,B. S. (1991). Fundam Appl. Toxicol 17, 347–360. Two- andthirteen-week toxicity studies were conducted using male andfemale F344/N rats and B6C3F1 mice. Animals were exposed tothe following concentrations of acetone in their drinking water:two-week studm 0; 5000; 10,000; 20,000; 50,000; or 100,000 ppmacetone. Thirteen-week rat and female mouse studies 0; 2500;5000; 10,000; 20,000; or 50,000 ppm acetone. Thirteen week malemice were exposed to 0; 1250; 2500; 5000; 10,000; or 20,000ppm acetone. Depressed body weight gain was restricted to the50,000 and 100,000 ppm exposure groups. Male and female miceexposed respectively to 20,000 or 50,000 ppm acetone for 2 weeksdeveloped hepatocellular hypertrophy. This change was not apparentafter 13 weeks of exposure although relative and alsolute liverweight was increased in high dose female mice. Bone marrow hypoplasiawas observed In 5/5 high dose (100,000 ppm) male rats duringthe 2-week studies. Treatment of male rats for 13 weeks resultedin a variety of mild and subtle hematological changes that oftenoccurred at relatively low levels of exposure (5000 ppm) andresembled those seen during the clinical condition of megaloblasticanemia Changes characteristic of hypogonadism (depressed spermmotility and cauda epididymal and epididymal weight and elevatedincidence of abnormal sperm) were observed in male rats raceiving50,000 ppm acetone for 13 weeks. The incidence and severityof a kidney laion that is morphologically similar to the spontaneouslyoccurring nephropathy among aging F-344 rats were increasedat 20,000 and 50,000 ppm acetone, respectively, in 13-week malerats. In summary, the effects of acetone were either subtlein nature or occurred during very high levels of exposure confirmingacetone's low level of toxicity. The daily levels of acetoneexposure were often several-fold greater than possibly encounteredby humans during the accidental consumption of contaminatedgroundwater (250 ppm; 5 mg/day) and frequently exceeded maximumlevels reported following acute toxic exposures (2,500 mg/kg).