A reference list of neurotoxicants based on CLP harmonised classifications

With the societal interest to decrease experimental animal testing for regulatory purposes, the need for reliable new approach methods (NAMs) has become evident. To ensure the continued safe use of chemicals, NAMs should perform ideally at a comparable or better level of sensitivity and specificity as the in vivo modalities that they aim to replace, especially if they are to be used for hazard assessment. The use of relevant reference substances, selected with transparent criteria, forms a cornerstone of developing and validating (in silico and in vitro) NAMs. Claims on sensitivity and specificity should be based on results generated with reference chemicals that were previously scrutinised by independent expert panels on whether the substance has a hazardous property. CLP (Regulation (EC) No 1272/2008 on the classification, labelling and packaging of substances and mixtures) forms a key pillar in EU chemicals management. The evaluation of all available information by the Committee for Risk Assessment (RAC) and their comparison to CLP classification criteria creates the opportunity to objectively compile lists of positive reference substances. We collated a reference list of neurotoxic substances to aid in the development of neurotoxicity NAMs. We screened CLP Annex VI and reflected on existing reference lists and mode of action data. The identified substances included industrial chemicals and active substances in plant protection products and biocidal products. This list of neurotoxicants is not an exhaustive consensus list, which ideally would be the result of combining this list with those generated by other authorities or expert groups.