HEMOGLOBIN ADDUCTS OF EPOXYBUTANEDIOL FROM EXPOSURE TO 1,3-BUTADIENE OR BUTADIENE EPOXIDES

Epoxybutanediol is one of the reactive metabolites of butadiene. It is formed via hydrolysis followed by oxidation of the primary metabolite of butadiene, epoxybutene, or via hydrolysis of diepoxybutane, a seco ndary metabolite of butadiene. Groups of male Sprague Dawley rats were treated by intraperitoneal injection of epoxybutene, epoxybutanediol or diepoxybutane. N-(2,3,4-Trihydroxybutyl)valine adducts in haemoglob in, formed from epoxybutanediol in its reaction with N-terminal valine , were measured using the N-alkyl Edman method followed by acetylation of the Edman derivatives and analysis by gas chromatography mass spec trometry. The same adducts were also measured in male Wistar rats expo sed to butadiene by inhalation and in a few workers with occupational exposure to butadiene. Haemoglobin binding indexes, HBI, (pmol adduct/ g per mu mol of alkylating agent, or, for butadiene, per ppm x h), wer e calculated. The HBI for epoxybutanediol (about 10) is comparable to that of ethylene oxide in the rat demonstrating a similar capacity of the two compounds to alkylate nucleophilic sites in vivo. The HBI of d iepoxybutane (about 8) for epoxybutanediol adduct formation is approxi mately the same as that of epoxybutanediol itself. Epoxybutanediol add uct formation was nonlinearly related to exposure in butadiene exposed rats. The epoxybutanediol-haemoglobin adduct levels were substantiall y higher than those of epoxybutene in both butadiene-exposed rats and humans suggesting an important role of epoxybutanediol in the toxicity of butadiene. Adducts of epoxybutanediol are probably useful for biom onitoring of human exposure to butadiene. (C) 1997 Elsevier Science Ir eland Ltd.