Limited hepatotoxic potential of acrylonitrile in rats
Silver, E.H.; Mccomb, D.J.; Kovacs, K.; Szabo, S.
Toxicology and Applied Pharmacology 64(1): 131-139
ISSN/ISBN: 0041-008X PMID: 7112577 DOI: 10.1016/0041-008x(82)90331-3
The possible hepatotoxicity of acrylonitrile (ACN) was investigated based on reports of decreased hepatic glutathione in rats and liver abnormalities in man after exposure to ACN. Male and female rats pretreated orally daily for 3 days with sodium phenobarbital (400 .mu.mol/kg) or with Aroclor 1254 (300 .mu.mol/kg) were given ACN (50, 75, 100 or 150 mg/kg) orally for 1, 2 or 3 days or 100 or 500 ppm ACN in drinking water for 21 days. Rats were killed 30 min or 24 h after 1 dose of ACN or on day-22 in the subacute study. Hepatic nonprotein SH (NP-SH) concentration and the activities in serum or sorbitol dehydrogenase (SDH) and alanine transaminase (GPT) were measured. The liver was examined grossly and microscopically. Hepatic NP-SH decreased significantly (39, 60, 74 and 81%) at 30 min after 50, 75, 100 or 150 mg ACN, respectively. In some experiments serum SDH was significantly elevated (.apprx. 4-fold) 24 h after 150 mg/kg ACN. Pretreatment with phenobarbital and Aroclor 1254 resulted in only a slight enhancement of the ACN-induced elevation in serum SDH or GPT activities. Serum SDH increased 60% in rats given 500 ppm ACN in drinking water. Focal superficial necrosis of the liver associated (P < 0.001) with hemorrhagic gastritis of a distended forestomach was found in rats necropsied 24 h after administration of 150 mg/kg ACN. Other than this superficial necrosis, light microscopy revealed only minor changes in liver tissue. EM disclosed no changes in the organelles of hepatocytes of rats treated for 21 days with ACN.