Assessment factors for human health risk assessment: A discussion paper

The general goal of this discussion paper is to contribute toward the furth er harmonization of human health risk assessment. It first discusses the de velopment of a formal, harmonized set of assessment factors. The status quo with regard to assessment factors is reviewed, that is, the type of factor s to be identified, the range of values assigned, as well as the presence o r absence of a scientific basis for these values. Options are presented for a set of default values and probabilistic distributions for assessment fac tors based on the state of the art. Methods of combining default values or probabilistic distributions of assessment factors are also described. Secon d, the effect parameter, the no-observed-adverse-effect level (NOAEL), is d iscussed. This NOAEL as selected from the toxicological database may be a p oor substitute for the unknown, true no-adverse-effect level (NAEL). New de velopments are presented with respect to the estimation of the NAEL. The al ready widely discussed Benchmark Dose concept can be extended to obtain an uncertainty distribution of the Critical Effect Dose (CED). This CED distri bution can be combined with estimated uncertainty distributions for assessm ent factors. In this way the full distribution of the Human Limit Value wil l be derived and not only a point estimate, whereas information on dose-res ponse relations is taken into account. Finally, a strategy is proposed for implementation of the new developments into human health risk assessments.