Kielhorn J, Melber C, Wahnschaffe U, Aitio A, Mangelsdorf I
Fraunhofer Institute for Toxicology and Aerosol Research with Drug Research and Clinical Inhalation, Hanover, Germany.
Environ Health Perspect. 2000 Jul;108(7):579-88. doi: 10.1289/ehp.00108579.
Vinyl chloride (VC) is both a known carcinogen and a regulated chemical, and its production capacity has almost doubled over the last 20 years, currently 27 million tons/year worldwide. According to recent reports it is still a cause for concern. VC has been found as a degradation product of chloroethylene solvents (perchloroethylene and trichloroethylene) and in landfill gas and groundwater at concentrations up to 200 mg/m(3) and 10 mg/L, respectively. Worldwide occupational exposure to VC still seems to be high in some countries (e.g., averages of approximately 1,300 mg/m(3) until 1987 in one factory), and exposure may also be high in others where VC is not regulated. By combining the most relevant epidemiologic studies from several countries, we observed a 5-fold excess of liver cancer, primarily because of a 45-fold excess risk from angiosarcoma of the liver (ASL). The number of ASL cases reported up to the end of 1998 was 197 worldwide. The average latency for ASL is 22 years. Some studies show a small excess risk for hepatocellular carcinoma, and others suggest a possible risk of brain tumors among highly exposed workers. Lung cancer, lymphomas, or leukemia do not seem to be related to VC exposure according to recent results. The mutation spectra observed in rat and human liver tumors (ASL and/or hepatocellular carcinoma) that are associated with exposure to VC are clearly distinct from those observed in sporadic liver tumors or hepatic tumors that are associated with other exposures. In rats, the substitution mutations found at A:T base pairs in the ras and p53 genes are consistent with the promutagenic properties of the DNA adduct 1,N(6)-ethenoadenine formed from VC metabolites. Risk assessments derived from animal studies seem to overestimate the actual risk of cancer when comparing estimated and reported cases of ASL.
氯乙烯（VC）既是一种已知的致癌物，也是一种受管制的化学品，在过去20年里其生产能力几乎翻了一番，目前全球年产量为2700万吨。根据最近的报告，它仍然令人担忧。VC已被发现是氯乙烯溶剂（全氯乙烯和三氯乙烯）的降解产物，在垃圾填埋气和地下水中的浓度分别高达200毫克/立方米和10毫克/升。在世界范围内，一些国家职业接触VC的情况似乎仍然很严重（例如，1987年之前一家工厂的平均接触量约为1300毫克/立方米），在其他未对VC进行管制的国家，接触量可能也很高。通过综合几个国家最相关的流行病学研究，我们发现肝癌发病率高出5倍，主要是因为肝血管肉瘤（ASL）的发病风险高出45倍。截至1998年底，全球报告的ASL病例数为197例。ASL的平均潜伏期为22年。一些研究表明肝细胞癌的发病风险略有增加，另一些研究则表明高暴露工人可能有患脑肿瘤的风险。根据最近的结果，肺癌、淋巴瘤或白血病似乎与VC接触无关。在与VC接触相关的大鼠和人类肝脏肿瘤（ASL和/或肝细胞癌）中观察到的突变谱与在散发性肝脏肿瘤或与其他暴露相关的肝脏肿瘤中观察到的突变谱明显不同。在大鼠中，ras和p53基因中A:T碱基对处发现的替代突变与由VC代谢产物形成的DNA加合物1,N(6)-乙烯腺嘌呤的促突变特性一致。在比较ASL的估计病例数和报告病例数时，来自动物研究的风险评估似乎高估了实际的癌症风险。
