A retrospective study on EU harmonised classifications for carcinogenicity to guide future research

Under European Regulation (EC) No 1272/2008 on the classification, labelling and packaging of substances and mixtures (CLP), chemicals can be classified as carcinogenic if they are considered to induce tumours, increase tumour incidence and/or malignancy, or shorten the time to tumour occurrence. Cancer classifications are divided into different hazard categories: Carc. 1A (known human carcinogen), Carc. 1B (presumed human carcinogen), Carc. 2 (suspected human carcinogen), and chemicals not classified for carcinogenicity. Selecting which classification is appropriate can be challenging, as judgements need to be made both on the existing hazard data and on its relevance to humans. One aspect to be considered in defining human relevance is a chemical's mode of action (MoA); the series of necessary key events that lead from an exposure to the adverse effect (in this case, tumours). This work aims to identify and discuss some of the features that have led ECHA's Committee for Risk Assessment (RAC) to decide upon harmonised cancer classifications for chemicals, and to prioritise future research on MoA and/or human relevance. RAC bases its decisions on cancer classification on both the weight-of-evidence (WoE) and strength-of-evidence (SoE) of this particular activity. Multiple factors contribute, including the species in which tumours are seen, and the relevance of the MoA to human health.