二氯甲烷对人类健康的影响:主要研究发现和科学问题

发布时间：2018-06-28 22:57

本文选题：氯甲烷 + 非霍奇金淋巴瘤　；参考：《环境与职业医学》2015年06期

【摘要】：[背景]美国EPA的综合风险信息系统(IRIS)在2011年11月完成了对二氯甲烷毒理学综述的更新。[目的]本述评总结了这一综述中的主要结果和关键问题,包括暴露来源、识别潜在的健康影响和更新的基于生理学的药代动力学(PBPK)建模方法。[方法]对基础研究进行全面回顾,并对PBPK模型进行评价。[讨论]在若干经口和吸入暴露的动物研究中发现了肝脏毒性;神经系统的影响也是需要关注的潜在研究领域。二氯甲烷被列为可能对人类具有致癌性,其主要的证据基础是在雄性和雌性B6C3F1小鼠(吸入暴露)的两个部位(肝和肺)和雄性B6C3F1小鼠(饮用水暴露)的一个部位具有致癌作用。最近有关二氯甲烷的流行病学研究(2000年以来发表的7篇造血系统癌症研究)提供了更多的数据,增加了人们对其与非霍奇金淋巴瘤和多发性骨髓瘤之间关联的关注。虽然数据库中仍存在诸多信息缺口,比如二氯甲烷基因毒性(即体内靶组织中的DNA加合物的形成和基因突变),DNA损伤测定的阳性结果与组织和/或物种谷胱甘肽-S-转移酶(GST)代谢活性的获得能力之间的关联,以及二氯甲烷诱发癌症的关键激活途径。IRIS评估中的创新之处在于专门针对推测的敏感基因型(GST-theta-1+/+)估计癌症风险,以及在PBPK建模中考虑生理学分布,该分布基于6个月至80岁所有个体的期望分布。[结论]2011年IRIS的二氯甲烷评估提供了对这一常用溶剂毒性的新认识。
[Abstract]:[background] EPA's Integrated risk Information system (IRIS) completed an update of dichloromethane toxicology in November 2011. [objective] this review summarizes the main findings and key issues in this review, including exposure sources, identification of potential health effects, and updated pharmacokinetics (PBPK) modeling methods based on physiology. [methods] basic research was reviewed and PBPK model was evaluated. Liver toxicity has been found in a number of oral and inhaled animal studies; neurological effects are also potential areas of concern. Dichloromethane is listed as possible carcinogenic to humans, and its main evidence is carcinogenic in two parts (liver and lung) of male and female B6C3F1 mice (inhalation exposure) and one part of male B6C3F1 mice (exposed to drinking water). Recent epidemiological studies on dichloromethane (seven studies on hematopoietic system cancer published since 2000) provide additional data and raise concerns about its association with non-Hodgkin 's lymphoma and multiple myeloma. Although there are still many information gaps in the database, For example, the genetic toxicity of dichloromethane (that is, the formation and mutation of DNA adducts in target tissues in vivo) and the correlation between the positive results of DNA damage determination and the ability of tissue and / or species to acquire the metabolic activity of glutathione -Stransferase (GST), And the key activation pathway for cancer induced by dichloromethane. The innovation in IRIS assessment is to estimate cancer risk specifically for speculated sensitive genotypes (GST-theta-1 /) and to consider physiological distribution in PBPK modeling. The distribution is based on the expected distribution of all individuals aged 6 months to 80 years. [conclusion] the 2011 IRIS assessment of dichloromethane provides a new understanding of this common solvent toxicity.
【分类号】：R114

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