CAR MoA Dossier Analysis Database

Data on mode of action (MoA) of rodent tumour formation have become an integral part of the information submitted in regulatory dossiers for some chemical substances registration or re-registration. Despite this, there is a lack of guidance or standardised approaches for addressing such results through evidence-based follow-up studies in dossiers within the agrochemical and chemical sectors. This instigates companies to proactively conduct extensive studies on vertebrates, which contradicts the principles of the 3Rs (Replacement, Reduction, and Refinement). To better understand the role that in vitro mechanistic studies already can play in decision-making we conducted an analysis focusing on one of the most common MoAs involved in rodent liver carcinogenicity: the constitutive androstane receptor (CAR) MoA, which accounts for about 25% of tumours induced in rodents by agrochemicals. We collected information from 36 harmonised classification and labelling (CLH) dossiers on the actual use and weight of in vitro mechanistic data used to evaluate positive results from rodent cancer bioassays.