The IARC re-classification of talc carcinogenicity: a move in the wrong direction?

The paper explores a content of the recent International Agency for Research on Cancer (IARC) Monograph (Volume 136) where pure talc was reclassified from the Group 2B (“Possibly carcinogenic to humans”) to the Group 2 A (“Probably carcinogenic to humans”). The Monograph is considered in the context of the history of the IARC program for classification of carcinogens as well as in the framework of basic principles of toxicological science. It is demonstrated that reclassification was made not based on any new scientific information available, but rather because of a change in some of the methodological approaches or preferences employed by IARC. In particular, it is demonstrated that there are significant mineralogical issues in characterization of talc by the recent IARC Monograph. It is shown why weight-of-evidence for carcinogenicity of pure talc in experimental animals cannot be estimated higher than “limited”, and in human study higher than “inadequate”. It will also be argued that utilization of separated mechanistic criteria (key characteristics of carcinogens) without contextual analysis and proven mode-of-action (MoA) can cause significant uncertainties in the determination of carcinogenicity in humans. There is a need for comprehensive risk assessment for various agents and processes, rather than just hazard identification that the IARC continues to exercise with questionable relevance for global cancer prevention.

本文探讨了近期发布的《国际癌症研究机构（International Agency for Research on Cancer，IARC）专刊》（第136卷）的相关内容，该专刊将纯滑石粉从2B组（“可能对人类致癌”）重新归类为2A组（“很可能对人类致癌”）。本次讨论将结合IARC致癌物分类项目的历史沿革，并纳入毒理学科学的基本原理框架之中。研究表明，此次重新分类并非基于任何已公开的全新科学证据，而是源于IARC所采用的部分方法论路径或偏好发生了转变。具体而言，本研究指出，新版IARC专刊在滑石粉的特征表征方面存在诸多重大矿物学问题。研究阐明了为何纯滑石粉在实验动物中的致癌性证据权重无法被评定为高于“有限”，而在人体研究中则无法高于“不足”。本文同时将论证：若脱离背景分析与已证实的作用模式（mode-of-action，MoA），单独使用机制性标准（即致癌物关键特征），会在人类致癌性判定中引发显著不确定性。当前亟需针对各类物质与过程开展全面的风险评估，而非仅进行危害识别——而IARC目前仍在推行的危害识别工作，其与全球癌症预防的相关性颇受质疑。