Critical appraisal of the expert knowledge elicitation (EKE) methodology to identify uncertainties in building cumulative assessment groups for craniofacial alterations.

The European Food Safety Authority (EFSA) conducted a retrospective cumulative dietary risk assessment (CRA) on active substances (AS) and metabolites included in the plant protection products registered in Europe which could provoke craniofacial alterations. Two Cumulative Assessment groups (CAGs) were established: one for alterations due to abnormal skeletal development (CAG-DAC) and one for head soft tissue alterations and brain neural tube defects (CAG-DAH). The probability that each substance is correctly assigned to the specific CAGs (CAG-membership probability) was assessed using weight of evidence and expert knowledge elicitation (EKE) techniques conducted for the six substances identified as risk drivers in each CAG. Four out of the six substances allocated to the CAG-DAC or to the CAG-DAH presented a large interval of uncertainty, with probability of belonging to the attributed CAG between 10 % and 70 % or 33-90 %, which makes it difficult to determine if the substances truly belong to the CAG. In the present work the probability ranges of each risk driver were reassigned according to the approximate probability scale recommended in the EFSA guidance on uncertainty analysis. It is proposed that AS with a high probability are to be included in the CAG and those with a low probability removed from the CAG. For compounds with very large probability ranges, uncertainty assessments would have to be redone to reach narrower probability ranges. Finally, whenever recent decisions on reproduction toxicity classifications made by the European Chemical Agency (ECHA) are available, these should be used to conclude on CAG memberships.