A physiological toxicokinetic model for 1,3-butadiene in rodents and man: Blood concentrations of 1,3-butadiene, its metabolically formed epoxides, and of haemoglobin adducts - Relevance of glutathione depletion
1997
A physiological toxicokinetic (PT) model is presented describing disposition and metabolism of 1,3-butadiene (BU) and 1,2-epoxy-3-butene (BMO) in rat, mouse and man, and of 1,2:3,4-diepoxybutane (BDI) in mice. It contains formation of BMO and BDI, intrahepatocellular first-pass hydrolysis of BMO, conjugation of BMO with glutathione (GSH) and GSH-turnover in the liver. Tissue:air partition coefficients of BU and BMO were determined experimentally. Haemoglobin (HB) adducts of BMO in rodents following exposure to BU were simulated and compared with published data. The model is compared with those published earlier. An attempt was made to compare the carcinogenic potential of BU in mice and rats with respect to the carcinogenic potentials of both epoxides.
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