Effect of n-hexane on the disposition and toxicity of the 1,3-butadiene metabolite 3-butene-1,2-diol.
3-Butene-1,2-diol (butenediol), a major metabolite of 1,3-butadiene (butadiene), can undergo either detoxification or biotransformation to potentially toxic metabolites, including 3,4-epoxy-1,2-butanediol and hydroxymethylvinyl ketone (HMVK). Butadiene exposure can occur concomitantly with hexanes, which share common biotransformation pathways with butadiene. To determine the potential influence of hexane co-exposure on butadiene toxicity, the present study examined the effect of n-hexane on butenediol disposition [as measured by urinary excretion of (N-acetyl-S-(3,4-dihydroxybutyl)-L-cysteine) (MI level)] and genotoxicity (as measured by the frequency of bone marrow micronucleated erythrocytes) and acute toxicity (as measured by body weight changes) in the rat. The results show that butenediol was not genotoxic to adult or immature rats but was acutely toxic to adult but not immature rats. The results also suggest that n-hexane co-exposure may attenuate the acute toxicity by butenediol in adult rats and that immature rats may be less sensitive than adults to the acute toxicity.
Iba
Michael M
MM
Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy and Environmental and Occupational Health Sciences Institute, Rutgers University, New Brunswick, NJ, USA. iba@eohsi.rutgers.edu
Bird
Michael G
MG
D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000737:chemistry / Q000652:urine; D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001854:Bone Marrow Cells / Q000187:drug effects; D002070:Butadienes / Q000737:chemistry / Q000378:metabolism*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D006018:Glycols / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity*; D006586:Hexanes / Q000494:pharmacology*; D008297:Male; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D023382:Toxicity Tests, Acute
D002070:Butadienes; D006018:Glycols; D006586:Hexanes; C088614:1-hydroxy-2-(N-acetylcysteinyl)-3-butene; C026385:n-hexane; C031763:1,3-butadiene; C034598:3-butene-1,2-diol; D000111:Acetylcysteine