本文選題：氯甲烷 + 非霍奇金淋巴瘤��； 參考：《環(huán)境與職業(yè)醫(yī)學(xué)》2015年06期

【摘要】：[背景]美國EPA的綜合風(fēng)險(xiǎn)信息系統(tǒng)(IRIS)在2011年11月完成了對二氯甲烷毒理學(xué)綜述的更新。[目的]本述評總結(jié)了這一綜述中的主要結(jié)果和關(guān)鍵問題,包括暴露來源、識別潛在的健康影響和更新的基于生理學(xué)的藥代動(dòng)力學(xué)(PBPK)建模方法。[方法]對基礎(chǔ)研究進(jìn)行全面回顧,并對PBPK模型進(jìn)行評價(jià)。[討論]在若干經(jīng)口和吸入暴露的動(dòng)物研究中發(fā)現(xiàn)了肝臟毒性;神經(jīng)系統(tǒng)的影響也是需要關(guān)注的潛在研究領(lǐng)域。二氯甲烷被列為可能對人類具有致癌性,其主要的證據(jù)基礎(chǔ)是在雄性和雌性B6C3F1小鼠(吸入暴露)的兩個(gè)部位(肝和肺)和雄性B6C3F1小鼠(飲用水暴露)的一個(gè)部位具有致癌作用。最近有關(guān)二氯甲烷的流行病學(xué)研究(2000年以來發(fā)表的7篇造血系統(tǒng)癌癥研究)提供了更多的數(shù)據(jù),增加了人們對其與非霍奇金淋巴瘤和多發(fā)性骨髓瘤之間關(guān)聯(lián)的關(guān)注。雖然數(shù)據(jù)庫中仍存在諸多信息缺口,比如二氯甲烷基因毒性(即體內(nèi)靶組織中的DNA加合物的形成和基因突變),DNA損傷測定的陽性結(jié)果與組織和/或物種谷胱甘肽-S-轉(zhuǎn)移酶(GST)代謝活性的獲得能力之間的關(guān)聯(lián),以及二氯甲烷誘發(fā)癌癥的關(guān)鍵激活途徑。IRIS評估中的創(chuàng)新之處在于專門針對推測的敏感基因型(GST-theta-1+/+)估計(jì)癌癥風(fēng)險(xiǎn),以及在PBPK建模中考慮生理學(xué)分布,該分布基于6個(gè)月至80歲所有個(gè)體的期望分布。[結(jié)論]2011年IRIS的二氯甲烷評估提供了對這一常用溶劑毒性的新認(rèn)識。
[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.
【分類號】：R114

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