Haemoglobin 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 secondary 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 haemoglobin, 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 spectrometry. The same adducts were also measured in male Wistar rats exposed to butadiene by inhalation and in a few workers with occupational exposure to butadiene. Haemoglobin binding indexes, HBI, (pmol adduct/g per mumol of alkylating agent, or, for butadiene, per ppm x h), were 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 diepoxybutane (about 8) for epoxybutanediol adduct formation is approximately the same as that of epoxybutanediol itself. Epoxybutanediol adduct formation was nonlinearly related to exposure in butadiene exposed rats. The epoxybutanediol-haemoglobin adduct levels were substantially 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 biomonitoring of human exposure to butadiene.