COT/COM/COC Annual Report 2021

COT Working Groups 2021

Last updated: 17 November 2022


 Report and Guidance of the Synthesis and Integration of Epidemiological and Toxicological Evidence Subgroup (SETE) of the Committee on Toxicity and the Committee on Carcinogenicity

1.150 The UK Committees on Toxicity (COT) and on Carcinogenicity (COC) regularly review epidemiological and toxicological evidence in their risk assessments. There is, therefore, a need for guidance on the approaches used by the Committees to integrate these evidence streams, both for scientific consistency and to ensure public transparency. To that end, the Committees established the Synthesising and Integration of Epidemiological and Toxicological Evidence Subgroup (SETE) to review and document current practice and provide applicable guidance.  

1.151 SETE recognised that issues on which advice from the Committees is sought varies considerably and hence the guidance proposed should be sufficiently flexible to address this. 

1.152 Scoping and problem formulation were identified as the crucial first step in the process. This ensures the right questions are asked, helps make the most efficient use of resources and identifies the most appropriate approaches to use in the assessment. An established system or guidance to assess the separate/different evidence streams should be followed where feasible. 

1.153 For both epidemiological and toxicological evidence, a prescriptive checklist or scoring approach is not recommended. However, identifying the strengths and weaknesses of studies is important. The decision-making process should be robust, transparent, evidence-based, defensible and documented but equally importantly, it should be easy to use. Collaboration and ongoing dialogue between epidemiologists, exposure experts and toxicologists are strongly advised. Information on mode of action (MOA) can be invaluable for evidence integration as it underpins weight of evidence considerations by providing the mechanistic link between empirical observation and biological plausibility. 

1.154 All lines of evidence should be considered, with no specific hierarchy a priori. One way to clearly depict the influence of the different lines of evidence on causality is via visual representation. Decisions on whether there is sufficient information to reach a conclusion or whether a causal relationship in humans is more likely or unlikely can be reached based on where the causal interference appears on a graph. It is important to begin with the initial estimate of causal interference at the centre of the graph. Depending on whether the toxicological, mechanistic or epidemiological evidence assessed supports or discounts (or has no clear influence on) a conclusion of causality, placement on the graph is then moved accordingly, either in a positive or negative direction. The movement is influenced by several factors, including the strength or weakness of the evidence, any relative weighing given to epidemiological and toxicological studies and the uncertainties associated with the data. As more information is included in the process and/or becomes available, the placement of the toxicological and/or epidemiological evidence can be easily adjusted and the impact on any possible conclusion easily seen. 

1.155 In contrast to other approaches, the above visualisation aims to provide a pictorial representation of the consensus views of a Committee on the influence of the different lines of evidence on causation, assessed by debate and agreement of scientific experts. In this way, it provides a more objective means of collating the views of the Committee and communicating the agreed conclusion of a Committee on the likelihood of causation. 

1.156 The conclusion should be stated, with an estimate of the overall uncertainty and, where appropriate, guidance on how data gaps could be filled. 

1.157 The full SETE report and guidance document (Annex 1) can be found on the COT website: SETE Outputs 

Please note, the guidance will be trialled by the COT for 2 years and then reviewed.  

Plant based drinks

1.158 Plant-based drinks have become increasingly popular in the United Kingdom (UK) both for individuals with an allergy to cows’ milk or lactose intolerance and those who wish to avoid dairy products for other ethical or cultural reasons. Three such drinks have been reviewed by the Committee – see paragraph 1.130.

1.159 SACN have also considered these drinks from a nutritional perspective. To bring these two strand together, a joint Working Group had been established. The Working Group started work In December 2021 and it is hoped that it will report in 2022.