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《关于1-溴丙烷的致癌物专论报告:致癌物专论01》

Report on Carcinogens Monograph on 1-Bromopropane: RoC Monograph 01.

出版信息

Rep Carcinog Monogr. 2013 Sep(01):1-168. doi: 10.22427/ROC-MGRAPH-01.

Abstract

The National Toxicology Program conducted a cancer evaluation on 1 bromopropane for possible listing in the Report on Carcinogens (RoC). The cancer evaluation is captured in the RoC monograph, which was peer reviewed in a public forum. The monograph consists of two components: (Part 1) the cancer evaluation, which reviews the relevant scientific information, assesses its quality, applies the RoC listing criteria to the scientific information, and provides the NTP recommendation for listing status for 1 bromopropane in the RoC, and (Part 2) the substance profile proposed for the RoC, containing the NTP's listing status recommendation, a summary of the scientific evidence considered key to reaching that decision, and data on properties, use, production, exposure, and Federal regulations and guidelines to reduce exposure to 1-bromopropane. This monograph provides an assessment of the available scientific information on 1 bromopropane, including human exposure and properties, disposition and toxicokinetics, cancer studies in experimental animals, and studies of mechanisms and other related effects, including relevant toxicological effects, genetic toxicology, and mechanisms of carcinogenicity. From this assessment, the NTP recommended that 1 bromopropane be listed as reasonably anticipated to be a human carcinogen in the RoC based on sufficient evidence from studies in experimental animals, which found inhalation exposure to 1-bromopropane caused skin tumors in male rats, large intestine tumors in female and male rats, and lung tumors in female mice. Also noted was that 1 bromopropane, either directly or via reactive metabolites, caused molecular alterations that typically are associated with carcinogenesis, including genotoxicity, oxidative stress, and glutathione depletion. These alterations, observed in mainly in vitro and toxicity studies in rodents, are relevant to possible mechanisms of human carcinogenicity and support the relevance of the cancer studies in experimental animals to humans.

摘要

美国国家毒理学计划对1-溴丙烷进行了癌症评估,以确定其是否可能被列入《致癌物报告》(RoC)。该癌症评估记录在RoC专论中,该专论在公开论坛上进行了同行评审。专论由两个部分组成:(第1部分)癌症评估,该部分审查相关科学信息,评估其质量,将RoC列入标准应用于科学信息,并提供美国国家毒理学计划关于1-溴丙烷在RoC中的列入状态的建议;(第2部分)为RoC提议的物质概况,其中包含美国国家毒理学计划的列入状态建议、被认为是做出该决定的关键科学证据的摘要,以及关于性质、用途、生产、接触情况以及减少接触1-溴丙烷的联邦法规和指南的数据。本专论对有关1-溴丙烷的现有科学信息进行了评估,包括人类接触情况和性质、处置和毒代动力学、实验动物的癌症研究,以及对包括相关毒理学效应、遗传毒理学和致癌机制在内的机制和其他相关效应的研究。根据对实验动物研究的充分证据,美国国家毒理学计划建议在RoC中将1-溴丙烷列为合理预期的人类致癌物,这些研究发现吸入1-溴丙烷会导致雄性大鼠皮肤肿瘤、雌性和雄性大鼠大肠肿瘤以及雌性小鼠肺部肿瘤。还指出,1-溴丙烷直接或通过反应性代谢物会引起通常与致癌作用相关的分子改变,包括遗传毒性、氧化应激和谷胱甘肽耗竭。这些改变主要在啮齿动物的体外和毒性研究中观察到,与人类致癌的可能机制相关,并支持实验动物癌症研究与人类的相关性。

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