Rice J M, Boffetta P
IARC Monographs Programme, International Agency for Research on Cancer, 69372 Lyon, Cedex 08, France.
Chem Biol Interact. 2001 Jun 1;135-136:11-26. doi: 10.1016/s0009-2797(01)00175-2.
1,3-Butadiene, isoprene and chloroprene have all been evaluated more than once by the IARC Monographs Programme on the Evaluation of Carcinogenic Risks to Humans, most recently in February 1998 (Volume 71). Summaries are available on-line at http://monographs.iarc.fr. 1,3-Butadiene is currently classified in Group 2A (probably carcinogenic to humans), on the basis of limited evidence for increased occupational cancer risk in humans plus sufficient evidence of carcinogenicity at multiple organ sites in rats and especially in mice exposed by inhalation. Four epidemiologic studies are available on cancer risk among workers exposed to 1,3-butadiene, one large study among styrene-butadiene rubber (SBR) workers, and one large and two small studies among 1,3-butadiene production workers. The results of the study of SBR workers suggest an association between butadiene exposure and leukaemia risk, which is consistent with the results of the large study of production workers. This latter study also suggested an increased risk of lymphoreticulosarcoma (ICD-8, 200). The major factors hampering the assessment of the available results are (i) possible misclassification of lymphoid and haematopoietic neoplasms, (ii) limitations in the assessment of past exposure (with the exception of the study of SBR workers) and (iii) a potential confounding effect of agents other than butadiene. Future research priorities include (i) the incorporation of newly developed biomarkers of exposure, (ii) the possible application of intermediate biomarkers, (iii) the replication of the study among SBR workers, possibly in Europe, and (iv) reanalysis of existing data in light of revisions of the classifications of leukaemias and lymphomas in the International Classification of Diseases for Oncology, Third Edition (2000). Isoprene is classified in Group 2B (possibly carcinogenic to humans), on the basis of sufficient evidence for carcinogenicity at multiple organ sites in both mice and rats, especially male mice, exposed by inhalation. No epidemiologic studies are available on cancer risk from occupational exposure to isoprene. Such studies could be conducted within the framework of existing or future studies of SBR workers, assuming that isoprene exposure can be disentangled from butadiene and styrene exposure. Chloroprene is classified in Group 2B on the basis of sufficient evidence for carcinogenicity at multiple organ sites in both mice and rats exposed by inhalation. Studies of chloroprene exposed workers now include chemical workers from the United States, China and Armenia as well as shoe workers from Russia. The results of the studies from China, Armenia and Russia suggest an excess risk of liver cancer. The risk of other neoplasms was not consistently increased. Limitations of available studies include possible bias from cohort enumeration, follow-up, and choice of reference population. In most studies the exposure assessment was poor, the possible confounding effect of co-exposures was not addressed and the statistical power was low. The pathology of the cases of liver cancer should be reviewed. Future research priorities include a replication of available studies in well-defined populations and the development of biomarkers of exposure.
国际癌症研究机构（IARC）人类致癌风险评估专论项目已不止一次对1,3 - 丁二烯、异戊二烯和氯丁二烯进行评估，最近一次是在1998年2月（第71卷）。总结内容可在http://monographs.iarc.fr在线获取。1,3 - 丁二烯目前被归类为2A组（可能对人类致癌），依据是人类职业性癌症风险增加的有限证据，以及大鼠尤其是吸入暴露的小鼠多个器官部位致癌性的充分证据。有四项关于接触1,3 - 丁二烯工人癌症风险的流行病学研究，一项是针对丁苯橡胶（SBR）工人的大型研究，以及一项针对1,3 - 丁二烯生产工人的大型研究和两项小型研究。SBR工人的研究结果表明丁二烯暴露与白血病风险之间存在关联，这与生产工人的大型研究结果一致。后一项研究还表明淋巴网状肉瘤（ICD - 8, 200）风险增加。妨碍对现有结果进行评估的主要因素包括：（i）淋巴和造血肿瘤可能的错误分类；（ii）过去暴露评估的局限性（丁苯橡胶工人的研究除外）；（iii）丁二烯以外其他因素的潜在混杂效应。未来的研究重点包括：（i）纳入新开发的暴露生物标志物；（ii）中间生物标志物的可能应用；（iii）可能在欧洲对SBR工人的研究进行重复；（iv）根据《国际肿瘤疾病分类》第三版（2000年）中白血病和淋巴瘤分类的修订对现有数据进行重新分析。异戊二烯被归类为2B组（可能对人类致癌），依据是吸入暴露的小鼠和大鼠多个器官部位致癌性的充分证据，尤其是雄性小鼠。没有关于职业接触异戊二烯癌症风险的流行病学研究。假设异戊二烯暴露能够与丁二烯和苯乙烯暴露区分开来，此类研究可在现有或未来丁苯橡胶工人研究的框架内进行。氯丁二烯基于吸入暴露的小鼠和大鼠多个器官部位致癌性的充分证据被归类为2B组。对接触氯丁二烯工人的研究目前包括来自美国、中国和亚美尼亚的化工工人以及来自俄罗斯的制鞋工人。中国、亚美尼亚和俄罗斯的研究结果表明肝癌风险过高。其他肿瘤的风险并未持续增加。现有研究的局限性包括队列枚举、随访和参考人群选择可能存在的偏差。在大多数研究中，暴露评估较差，未解决共同暴露的可能混杂效应，且统计效力较低。应审查肝癌病例的病理情况。未来的研究重点包括在明确界定的人群中重复现有研究以及开发暴露生物标志物。
