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

Gy A. Csanády; P. E. Kreuzer; C. Baur; J. G. Filser

doi:10.1016/0300-483X(96)03461-0

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

Gy A. Csanády, P. E. Kreuzer, C. Baur, J. G. Filser

Research output: Contribution to journal › Article › peer-review

38 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	300-305
Number of pages	6
Journal	Toxicology
Volume	113
Issue number	1-3
DOIs	https://doi.org/10.1016/0300-483X(96)03461-0
State	Published - 28 Oct 1996
Externally published	Yes

Keywords

1,2-epoxy-3-butene
1,2:3,4-diepoxybutane
1,3-butadiene
glutathione
hae moglobin adducts
humans
mice
physiological toxicokinetic model
rats
toxicokinetics

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title = "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",

abstract = "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.",

keywords = "1,2-epoxy-3-butene, 1,2:3,4-diepoxybutane, 1,3-butadiene, glutathione, hae moglobin adducts, humans, mice, physiological toxicokinetic model, rats, toxicokinetics",

author = "Csan{\'a}dy, {Gy A.} and Kreuzer, {P. E.} and C. Baur and Filser, {J. G.}",

year = "1996",

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doi = "10.1016/0300-483X(96)03461-0",

language = "English",

volume = "113",

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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. / Csanády, Gy A.; Kreuzer, P. E.; Baur, C. et al.
In: Toxicology, Vol. 113, No. 1-3, 28.10.1996, p. 300-305.

Research output: Contribution to journal › Article › peer-review

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AU - Filser, J. G.

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AB - 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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KW - 1,2:3,4-diepoxybutane

KW - 1,3-butadiene

KW - glutathione

KW - hae moglobin adducts

KW - humans

KW - mice

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KW - rats

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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

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Keywords

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