Development of a confidence index for choice of Toxicity Reference Value

Abstract

Toxicological Reference Values (TRVs) are developed to protect humans exposed either by oral or inhalation routes. They are derived for threshold or non-threshold effects, depending on the mechanism of action of each substance. These values are issued by several international organisms (WHO, US EPA, ATSDR, OEHHA, ANSES, EFSA,...) and used in risk assessment. If several values are available, risk assessors may have to exert an expert judgment to choose the most appropriate. The confidence given to the selected value should be considered when interpreting the conclusions of the risk assessment. In order to make this choice transparent and consistent between assessors, we propose to associate each choice with a confidence index, based on commonly accepted criteria. To develop this index, the main parameters influencing quality of a TRV were identified and structured by groups of key elements. Three criteria are defined corresponding to experimental vs.human study, TRV elaboration method and complementary elements. A questionnaire was designed using factorial experimental design in order to collect the opinions of toxicological expert on the weight to be given to each parameter. The experiment was conducted in two steps. In the first part, experts were asked to score artificial cases in order to evaluate the most critical parameters. The second part consisted in four case studies used for validation of the confidence index. Preliminary results show that a confidence index with four levels corresponding to high confidence, medium confidence, moderate confidence, and retained by default can be proposed.