Species and tissue differences in the toxicity of 3-butene-1,2-diol in male Sprague-Dawley rats and B6C3F1 mice.
3-Butene-1,2-diol (BDD) is a major metabolite of 1,3-butadiene (BD), but the role of BDD in BD toxicity and carcinogenicity remains unclear. In this study, the acute toxicity of BDD was investigated in male Sprague-Dawley rats and B6C3F1 mice. Of the rats given 250 mg/kg BDD, 2 out of 4 died within 24 h; rats experienced hypoglycemia, significant alterations of liver integrity tests, and had lesions in the liver 4 h after treatment, but no lesions were detected in extrahepatic tissues. Rat hepatic GSH and GSSG levels were significantly depleted at both 1 and 4 h after the BDD treatment. Rats administered 200 mg/kg BDD also had liver lesions but no death or hypoglycemia was observed four or 24 h after treatment; these rats had depleted hepatic GSH and GSSG levels at 1 h but not at 4 or 24 h after treatment. Mice administered 250 mg/kg BDD exhibited modest alterations of liver integrity tests, but no death, hypoglycemia, or lesions in any tissue, and hepatic GSH and GSSG levels were depleted at 1 h but not at 4 h. The plasma half-life of BDD was four times longer in rats than in mice. Additional studies in rats showed the depletion of hepatic GSH and GSSG preceded the BDD-induced hypoglycemia and hepatotoxicity. Thus, the long half-life of BDD in rat plasma and the sustained depletion of hepatic GSH and GSSG may in part explain the higher sensitivity of the rat to BDD-induced hepatotoxicity. Furthermore, the results indicate that BDD may play a role in BD-induced toxicity.
Sprague
Christopher L
CL
Department of Comparative Biosciences and the Molecular and Environmental Toxicology Center, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Phillips
Lynette A
LA
Young
Karen M
KM
Elfarra
Adnan A
AA
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D005978:Glutathione / Q000097:blood; D006018:Glycols / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D006207:Half-Life; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D014018:Tissue Distribution
D004785:Environmental Pollutants; D006018:Glycols; D005978:Glutathione; C034598:3-butene-1,2-diol