title: Novel and existing data for a future physiological toxicokinetic model of ethylene and its metabolite ethylene oxide in mouse, rat, and human.
abstract: The olefin ethylene is a ubiquitously found gas. It originates predominantly from plants, combustion processes and industrial sources. In mammals, inhaled ethylene is metabolized by cytochrome P450-dependent monooxygenases, particularly by cytochrome P450 2E1, to ethylene oxide, an epoxide that directly alkylates proteins and DNA. Ethylene oxide was mutagenic in vitro and in vivo in insects and mammals and carcinogenic in rats and mice. A physiological toxicokinetic model is a most useful tool for estimating the ethylene oxide burden in ethylene-exposed rodents and humans. The only published physiological toxicokinetic model for ethylene and metabolically produced ethylene oxide is discussed. Additionally, existing data required for the development of a future model and for testing its predictive accuracy are reviewed and extended by new gas uptake studies with ethylene and ethylene oxide in B6C3F1 mice and with ethylene in F344 rats.
authors: Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München, Neuherberg, Germany; Institut für Toxikologie und Umwelthygiene, Technische Universität München, München, Germany. Electronic address: johannes.filser@helmholtz-muenchen.de.
authors: Johannes Georg
authors: JG
authors: Filser
authors: Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München, Neuherberg, Germany.
authors: Anna
authors: A
authors: Artati
authors: Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München, Neuherberg, Germany.
authors: Qiang
authors: Q
authors: Li
authors: Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München, Neuherberg, Germany.
authors: Christian
authors: C
authors: Pütz
authors: Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München, Neuherberg, Germany.
authors: Brigitte
authors: B
authors: Semder
authors: Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München, Neuherberg, Germany; Institut für Toxikologie und Umwelthygiene, Technische Universität München, München, Germany.
authors: Dominik
authors: D
authors: Klein
authors: Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München, Neuherberg, Germany.
authors: Winfried
authors: W
authors: Kessler
mesh_terms: D000475:Alkenes / Q000378:metabolism; D000818:Animals; D002273:Carcinogens / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005027:Ethylene Oxide / Q000378:metabolism*; D005030:Ethylenes / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D051381:Rats; D011916:Rats, Inbred F344; D066007:Toxicokinetics
chemical_list: D000475:Alkenes; D002273:Carcinogens; D005030:Ethylenes; D003577:Cytochrome P-450 Enzyme System; C036216:ethylene; D019392:Cytochrome P-450 CYP2E1; D005027:Ethylene Oxide
keywords: Ethylene; Ethylene oxide; Human; Mouse; Rat