ABSTRACT
Chemical-specific adjustment factors (CSAF) provide for the incorporation of quantitative data on interspecies differences or human variability in either toxicokinetics or toxicodynamics to replace appropriately weighted components of default uncertainty factors commonly adopted in defining health-based guidance values. This chapter explores the application of CSAFs in the context of developed extensions to mode of action (MOA) frameworks to consider weight of evidence for human relevance through presentation of a relevant case study. These frameworks outline a basis for transparent delineation of expert informed judgment and as contribute to harmonization of approaches to hazard characterization for cancer and noncancer effects. The development of CSAF requires an understanding of MOA for the critical effect under consideration, in particular, whether or not effects are induced by the parent compound or a metabolite. The relevance of the population studied must also be considered in the development of a CSAF.
