Ninety-Day Oral Toxicity Study of Dibromochloromethane in Sprague-Dawley Rats

Abstract

Male and female Sprague-Dawley rats received dibromochloromethane daily by gavage to evaluate its subchronic toxicity. Dose levels were 0, 50, 100, and 200 mg.(kg-day)-1, with 10 animals/sex/group for 90 consecutive days. Corn oil was used as the vehicle. No changes were found in mortality, clinical signs, ophthalmoscopic examinations, or hematology that were considered to be related to treatment. Mean final body weight and body weight gain (weeks 0-13) were significantly decreased in male and female high dose animals relative to the vehicle control. Food consumption was decreased in males in a dose-related fashion, reaching statistical significance at the highest treatment level. Indications of hepatotoxicity in the clinical chemistry included elevated alanine amino-transferase (mid and high dose males) and alkaline phosphatase (high dose males and females). Increased serum creatinine (mid- and high dose males and high dose females) and decreased potassium (high dose males) were considered to be suggestive of nephrotoxicity. Absolute and relative weights of several organs in male and female animals were depressed and were related to the decreased body weights. The decreases in brain and thymic weights, and increases in liver and kidney weight (female only) were considered to be treatment related. Histopathological changes included findings of lipidosis of the liver and slight to moderate degenerative changes within the proximal tubular cells of the kidney. Based on the results of this study, the (LOAEL) lowest observed adverse effect level for DCBM when administered to Sprague-Dawley rats in corn oil gavage was 50 mg.(kg-day)-1.