苯乙烯是用于制造聚合物产品的重要的高产量化学品。2018年,国际癌症研究机构将苯乙烯归类为可能对人类致癌;国家毒理学计划将苯乙烯列为合理预期的人类致癌物。苯乙烯及其主要代谢产物的遗传毒性文献,苯乙烯7,8-氧化物(SO),始于1970年代。经济合作与发展组织(OECD)最近更新了大多数遗传毒性测试指南,为标准诱变性/致病性测定的测定进行和数据评估提出实质性的新建议。因此,对苯乙烯和SO的体外和体内啮齿动物诱变性/诱变性研究进行了严格审查,根据经合组织的最新建议,是及时的。这项关键审查考虑了一项研究是否被优化设计,进行了,并对其进行了解释,并对苯乙烯/SO的诱变性/诱变性的证据进行了严格的评估。总结了有关苯乙烯/SO诱导其他类型的遗传毒性终点的能力的信息,但没有严格审查。我们得出结论,当苯乙烯代谢为SO时,它可以形成DNA加合物,并且可以获得阳性的体外致突变性/诱变性结果。SO在细菌和体外小鼠淋巴瘤基因突变测定中具有诱变性。没有发现啮齿动物体内突变研究。SO在培养的哺乳动物细胞中具有致裂性。尽管体外试验给出了积极的反应,苯乙烯/SO在啮齿类动物体内不是致裂/不致畸形的。除了提供有关苯乙烯的最新信息外,这篇综述展示了新的OECD指南对具有大型遗传毒理学数据库的化学品的应用,这些数据库的公布结果可能可靠,也可能不可靠.环境。Mol.诱变剂.2019.©2019Wiley期刊,Inc.
Styrene is an important high production volume chemical used to manufacture polymeric products. In 2018, International Agency for Research on Cancer classified styrene as probably carcinogenic to humans; National Toxicology Program lists styrene as reasonably anticipated to be a human carcinogen. The genotoxicity literature for
styrene and its primary metabolite,
styrene 7,8-oxide (SO), begins in the 1970s. Organization of Economic Cooperation and Development (OECD) recently updated most genotoxicity test guidelines, making substantial new recommendations for assay conduct and data evaluation for the standard mutagenicity/clastogenicity assays. Thus, a critical
review of the in vitro and in vivo rodent mutagenicity/clastogenicity studies for
styrene and SO, based on the latest OECD recommendations, is timely. This critical
review considered whether a study was optimally designed, conducted, and interpreted and provides a critical assessment of the evidence for the mutagenicity/clastogenicity of styrene/SO. Information on the ability of styrene/SO to induce other types of genotoxicity endpoints is summarized but not critically reviewed. We conclude that when styrene is metabolized to SO, it can form DNA adducts, and positive in vitro mutagenicity/clastogenicity results can be obtained. SO is mutagenic in bacteria and the in vitro mouse lymphoma gene mutation assay. No rodent in vivo mutation studies were identified. SO is clastogenic in cultured mammalian cells. Although the in vitro assays gave positive responses, styrene/SO is not clastogenic/aneugenic in vivo in rodents. In addition to providing updated information for
styrene, this
review demonstrates the application of the new OECD guidelines for chemicals with large genetic toxicology databases where published results may or may not be reliable. Environ. Mol. Mutagen. 2019. © 2019 Wiley Periodicals, Inc.