Baan Robert A
Carcinogen Identification and Evaluation Group, WHO-International Agency for Research on Cancer, Lyon, France.
Inhal Toxicol. 2007;19 Suppl 1:213-28. doi: 10.1080/08958370701497903.
In February 2006, an IARC Monographs Working Group reevaluated the carcinogenic hazards to humans of carbon black, titanium dioxide, and talc, which belong to the group of poorly soluble, low-toxicity particles. The review of the relevant literature and the evaluations by the Working Group will be published in Volume 93 of the IARC Monographs series. This article summarizes the Working Group's conclusions. Epidemiological studies among workers in carbon black production and in the rubber industry provided inadequate evidence of carcinogenicity. The overall data from cancer studies in rodents exposed to carbon black provided sufficient evidence of carcinogenicity. The Working Group evaluated carbon black as possibly carcinogenic to humans, Group 2B. Reviewing the epidemiological studies in the titanium dioxide production industry, the Working Group concluded that there is inadequate evidence of carcinogenicity. Overall, the results from rodent cancer studies with titanium dioxide were considered to provide sufficient evidence. Titanium dioxide was evaluated as possibly carcinogenic to humans, Group 2B. Epidemiological studies on talc miners and millers provided inadequate evidence of carcinogenicity of inhaled talc not containing asbestos or asbestiform fibers. The evidence from rodent cancer studies was considered limited. The Working Group evaluated inhaled talc not containing asbestos or asbestiform fibers as not classifiable as to its carcinogenicity to humans, Group 3. The Working Group noted that prolonged exposure to inhaled particles at sufficiently high concentrations in experimental animals may lead to impairment of normal clearance mechanisms in the alveolar region of the lung, resulting in a continued buildup of particles that eventually leads to excessive lung burdens accompanied by chronic alveolar inflammation. The inflammatory response may give rise to increased generation of reactive oxygen species, cell injury, cell proliferation, fibrosis, induction of mutations, and, ultimately, cancer. Since many of these steps also occur in workers in dusty jobs, such as coal miners, data on cancer in animals obtained under conditions of impaired lung clearance were considered relevant to humans. In addition, impaired lung clearance in rodents exposed to ultrafine particles occurs at much lower mass concentrations than with fine particles, which adds to the human relevance.
2006年2月,国际癌症研究机构(IARC)专论工作组重新评估了炭黑、二氧化钛和滑石粉对人类的致癌风险,这些物质属于难溶性、低毒性颗粒类别。相关文献综述及工作组评估结果将发表于《IARC专论》系列第93卷。本文总结了工作组的结论。炭黑生产及橡胶行业工人的流行病学研究未提供充分的致癌证据。啮齿动物炭黑暴露致癌研究的总体数据提供了充分的致癌证据。工作组将炭黑评估为对人类可能致癌,2B组。审查二氧化钛生产行业的流行病学研究后,工作组得出结论,致癌证据不足。总体而言,啮齿动物二氧化钛致癌研究结果被认为提供了充分证据。二氧化钛被评估为对人类可能致癌,2B组。滑石矿工和加工工人的流行病学研究未提供吸入不含石棉或石棉状纤维滑石粉致癌的充分证据。啮齿动物癌症研究证据有限。工作组将吸入不含石棉或石棉状纤维的滑石粉评估为对人类致癌性无法分类,3组。工作组指出,实验动物长期吸入足够高浓度的颗粒可能导致肺肺泡区域正常清除机制受损,导致颗粒持续积聚,最终导致肺部负担过重并伴有慢性肺泡炎症。炎症反应可能导致活性氧生成增加、细胞损伤、细胞增殖、纤维化、诱导突变,最终引发癌症。由于许多这些步骤也发生在从事粉尘作业的工人(如煤矿工人)身上,因此在肺清除功能受损条件下获得的动物癌症数据被认为与人类相关。此外,与细颗粒相比,暴露于超细颗粒的啮齿动物肺清除功能受损时的质量浓度要低得多,这增加了与人类的相关性。