Framework for classifying chemicals for repeat dose toxicity using NAMs

ECETOC has developed a NAMs based classification system for “human systemic toxicity” mainly focussed on repeat dose toxicity, similar to the assessment carried out in classification for ‘Specific Target Organ Toxicity—Repeated Exposure’ (STOT-RE) based on ECETOC’s Tiered Approach (Ball et al. 2022) integrating three lines of evidence: In silico predictions, In vitro bioavailability and PBK modelling, In vitro bioactivity assays. This publication was also part of EPAA’s ‘NAM Designathon 2023’ challenge for human toxicity, looking to identify a classification system capable of categorising chemicals based on their bioactivity and bioavailability properties determined using non-animal methodologies (Worth et al. 2025).