Abstract

BACKGROUND: Few methods are available for transparently combining different evidence streams for chemical risk assessment to reach an integrated conclusion on the probability of causation. Hence, the UK Committees on Toxicity (COT) and on Carcinogenicity (COC) have reviewed current practice and developed guidance on how to achieve this in a transparent manner, using graphical visualisation. METHODS/APPROACH: All lines of evidence, including toxicological, epidemiological, new approach methodologies, and mode of action should be considered, taking account of their strengths/weaknesses in their relative weighting towards a conclusion on the probability of causation. A qualitative estimate of the probability of causation is plotted for each line of evidence and a combined estimate provided. DISCUSSION/CONCLUSIONS: Guidance is provided on integration of multiple lines of evidence for causation, based on current best practice. Qualitative estimates of probability for each line of evidence are plotted graphically. This ensures a deliberative, consensus conclusion on likelihood of causation is reached. It also ensures clear communication of the influence of the different lines of evidence on the overall conclusion on causality. Issues on which advice from the respective Committees is sought varies considerably, hence the guidance is designed to be sufficiently flexible to meet this need.