SUBCHRONIC TOXICITY STUDY OF 1,1-DICHLORO-2-PROPANONE IN SPRAGUE-DAWLEY RATS

Groups of 10 male and 10 female Sprague-Dawley rats were administered 1,1-dichloro-2-propanone in corn oil by gavage at 0, 10, 20, 40, or 80 mg/kg/day for 90 consecutive days. Food and water consumption, body and organ weights, organ-to-body weight ratios, hematology, and clinical chemistry parameters were determined. Gross and microscopic pathology examinations also were conducted. No treatment-related mortality was observed during the study; however, liver, forestomach, and kidney toxicity was evident. Liver changes consisted of cytoplasmic alteration, cytomegaly, karyomegaly, and bile duct hyperplasia. These occurred with significance of p less-than-or-equal-to 0.05 at or above 10 mg/kg/day in both sexes. The forestomach lesions included hyperkeratosis and epithelial hyperplasia in both sexes at 40 and 80 mg/kg/day, and ulcerations at 80 mg/kg/day. Also, an increased incidence and severity of spontaneously occurring chronic progressive nephropathy was most apparent in high dose males. Increases in organ-to-body weight ratios were noted for the liver and kidneys in females at the highest dose level and in males at the two highest dose levels. Serum enzymes (ALT, AST, and LDH) were increased in females and decreased in males. Based on liver lesions and biochemical changes, it was concluded that there was no experimentally definable NOAEL.