The acute toxicity of 2,3,4,7,8-pentachlorodibenzofuran (4PeCDF) in the male Fischer rat

• Published in: Fundamental and applied toxicology 1988-08, Vol.11 (2), p.236-249
• Main Authors: Brewster, David W., Uraih, Linda C., Birnbaum, Linda S.
• Format: Article
• Language: English
• Subjects: Animals; Benzofurans - blood; Benzofurans - toxicity; Bile Acids and Salts - metabolism; Biological and medical sciences; Body Weight - drug effects; Cholesterol - blood; Cytochrome P-450 CYP1A1; Cytochrome P-450 Enzyme System - metabolism; Environmental pollutants toxicology; General aspects; Lethal Dose 50; Liver - enzymology; Liver - pathology; Macaca mulatta; Male; Medical sciences; Organ Size - drug effects; Oxidoreductases - metabolism; Rats; Rats, Inbred F344; Toxicology; Triglycerides - blood
• ISSN: 0272-0590; 1095-6832
• DOI: 10.1016/0272-0590(88)90148-0

Polychlorinated dibenzofurans are ubiquitous environmental pollutants which have great potential for human exposure. To characterize the toxicity of 2,3,4,7,8-pentachlorodibenzofuran (4PeCDF), male F344 rats were administered a single oral dose of 0, 100, 250, 500, 1000, or 2000 μg 4PeCDF/kg. A progressive and dose-dependent loss of body weight was evident by 3 days after treatment. Signs of toxicity included piloerection, hair loss, hypoactivity, morbidity, and death. Death occurred as soon as 14 days after treatment and continued throughout the 35-day observation period. The LD50/35 was estimated to be 916 μg/kg with a 95% confidence interval of 565–1484 μg/kg. Dose-dependent increases were observed in serum cholesterol, triglyceride, and bile acid concentrations and in sorbitol dehydrogenase and aspartate aminotransferase activities. The hematocrit, hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin concentrations were depressed in a dose-dependent fashion. Hepatic ethoxyresorufin- O-deethylase (EROD) activity was increased in all treatment groups approximately 25 times above that of control animals. Lymphoid depletion in the thymus and spleen was observed in the three highest doses and thymic atrophy was present at all dose levels. Absolute liver weight and the liver: body weight ratio were significantly increased above controls. Hepatotoxicity was dose-dependent and was characterized by lipid accumulation resulting in hepatocytomegaly. Epithelial hyperplasia and focal ulcerations of the forestomach was observed in animals administered 500 μg 4PeCDF/kg. Spontaneous cardiomyopathy was exacerbated by treatment with 2000 μg/kg. Since 4PeCDF and 2,3,7,8-tetrachlorodibenzo- p-dixin (TCDD) produce a similiar spectrum of toxic effects, the biochemical mechanism(s) of toxicity for these chemicals may be similar.