A UK framework for the assessment and integration of different scientific evidence streams in chemical risk assessment.

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.

Considering evidence: The approach taken by the Hazardous Substances Advisory Committee in the UK.

The Hazardous Substances Advisory Committee (HSAC) provides expert advice to UK officials, Ministers and other relevant bodies on the protection of the environment, and human health via the environment, from potentially hazardous substances and articles. Hazardous substances are often the subject of controversy, on which individuals, and different groups in society, hold divergent views. This paper details the approach taken by HSAC when considering the evidence to provide advice on hazardous substances. Firstly HSAC reviews the range of evidence and determines its quality considering: transparency of aims, the methodology and results, completeness, independent review and accessibility. HSAC does not follow one explicit methodology as the wide range of hazardous substances we consider means they need to be addressed on a case by case basis. Most notably HSAC considers the evidence in the wider context, being aware of factors that influence individuals in their decision making when receiving a HSAC opinion e.g. trust in the source of the evidence, defensibility, conformity to a 'world view' and framing. HSACs also reflect on its own perspectives with the aim of addressing bias by the diversity of its membership. The Committee's intention, in adopting this rounded approach, is to reach opinions that are robust, relevant and defensible.

The in vitro mammalian chromosome aberration test.

The short-term in vitro mammalian cell chromosome aberration test is used to assess potential genotoxic hazard of test substances. Mammalian cells are cultured in vitro, exposed to a test substance, harvested, and the frequency of asymmetrical structural chromosome aberrations is measured. Human peripheral blood lymphocytes do not normally divide. The assessment of the effects of cyclophosphamide on lymphocytes, stimulated to divide in whole blood cultures in vitro, is described. Procedures that are important in generating accurate results are emphasised, to avoid false positive results. The study design for a regulatory assay, the use of established cell lines, alternative methods of measuring cytotoxicity and analysis of results are included.