甲苯二异氰酸酯(TDI)致癌性的综合评估

甲苯二异氰酸酯(TDI)被数家机构分类为可能的人类致癌物,其主要依据为动物实验发现对啮齿动物经灌胃暴露TDI后肿瘤发生率升高。基于研究结果的可靠性以及一致性,综合评估了现有研究数据是否支持这一分类。结果显示现有的流行病学数据不足以有力证明TDI为人类致癌物。动物实验研究表明,吸入接触TDI并不导致肿瘤发生。经灌胃暴露后观察到的肿瘤很可能是由于TDI转化为已知的啮齿动物致癌物甲苯二胺(TDA)所致。在TDI吸入暴露的体内实验中,当由TDI转化生成的TDA不能达到具有显著生物学效应的浓度时,TDI对啮齿动物或人类都没有遗传毒性。由于哺乳动物在生理性接触条件下TDI不能转变成TDA,所以对人类而言,TDI接触与致癌效应之间无直接的显著因果关系。因此虽然在如灌胃等非生理暴露的条件下,TDI可能的人类致癌物的分类是正确的,但本文对其致癌研究数据的合理评估和正确理解有助于将产品监管力度集中于与职业暴露更相关的有害健康效应上。

Evaluation of the Carcinogenicity of Toluene Diisocyanate

Toluene diisocyanate (TDI) is classified by several agencies as a possible human carcinogen, based on increased tumor incidences in rodents treated with TDI by oral gavage. We evaluated whether the available data support this classification, focusing on the quality of available studies and the consistency of results. The epidemiology data are not sufficiently robust to support TDI as a human carcinogen. The experimental animal studies indicate that TDI does not induce tumors in rats or mice after inhalation exposure. Tumors observed after oral gavage exposure are most likely due to the conversion of TDI to toluene diamine (TDA), a known rodent tumorigen. TDI is not genotoxic in rodents or humans after inhalation exposure, when TDA is not formed to a biologically significant degree. We conclude that a causal relationship between TDI exposure and carcinogenic effects is not plausible in humans, because the conversion of TDI to TDA does not occur in mammalian species under physiological exposure conditions. Thus, although the classification of TDI as a possible human carcinogen may be accurate for non-physiological exposures, a better understanding of the derivation of the data will allow for the proper focus to be placed on product stewardship efforts, which is more relevant to occupational exposure.