新型和现有数据，用于构建未来的乙烯及其代谢物环氧乙烷在小鼠、大鼠和人体中的生理毒代动力学模型。

Novel and existing data for a future physiological toxicokinetic model of ethylene and its metabolite ethylene oxide in mouse, rat, and human.

机构信息

Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München, Neuherberg, Germany; Institut für Toxikologie und Umwelthygiene, Technische Universität München, München, Germany.

Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München, Neuherberg, Germany.

出版信息

Chem Biol Interact. 2015 Nov 5;241:76-86. doi: 10.1016/j.cbi.2015.04.002. Epub 2015 Apr 10.

DOI:10.1016/j.cbi.2015.04.002

PMID:25868680

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.

摘要

烯烃乙烯是一种普遍存在的气体。它主要来源于植物、燃烧过程和工业来源。在哺乳动物中，吸入的乙烯被细胞色素 P450 依赖性单加氧酶代谢，特别是细胞色素 P450 2E1，生成环氧乙烷，一种直接烷化蛋白质和 DNA 的环氧化物。环氧乙烷在昆虫和哺乳动物体内外具有致突变性，并在大鼠和小鼠中具有致癌性。生理毒代动力学模型是估计暴露于乙烯的啮齿动物和人类中环氧乙烷负担的最有用工具。讨论了唯一发表的用于乙烯和代谢产生的环氧乙烷的生理毒代动力学模型。此外，通过 B6C3F1 小鼠中乙烯和环氧乙烷以及 F344 大鼠中乙烯的新气体摄取研究，审查并扩展了开发未来模型和测试其预测准确性所需的现有数据。