Guidance for Derivation of Chemical-Specific Adjustment Factors (CSAF)—Development and Implementation

Abstract

This manuscript addresses the content of and considerations in the implementation of guidance in the use of kinetic and dynamic data to inform quantitatively extrapolations for inter-species differences and human variability in dose response assessment developed in a project of the International Programme on Chemical Safety (IPCS) initiative on Harmonisation of Approaches to the Assessment of Risk from Exposure to Chemicals. The guidance has been developed and refined through a series of planning and technical meetings and larger workshops of a broad range of participants from academia, government agencies and the private sector.The guidance for adequacy of data for replacement of defaults for interspecies differences and human variability commonly adopted in the derivation of Tolerable or Acceptable Intakes is presented principally through illustrative reference to case examples. The relevant guidance is addressed in the context of several generic categories, including determination of the active chemical species, choice of the appropriate kinetic parameter or endpoint (dynamic component) and nature of experimental data, the latter, which includes reference to the relevance of population, route and dose and the adequacy of the number of subjects/samples