Guidelines for application of chemical-specific adjustment factors in dose/concentration-response assessment.

This manuscript addresses guidance in the use of kinetic and dynamic data to inform quantitatively extrapolations for interspecies 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 common defaults for interspecies differences and human variability is presented in the context of several generic categories including: determination of the active chemical species, choice of the appropriate metric (kinetic components) or endpoint (dynamic components) 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. The principal objective of this guidance developed primarily as a resource for risk assessors, is to foster better understanding of the components of and criteria for adequacy of chemical-specific data to quantitate interspecies differences and human variability in kinetics and dynamics. It is anticipated that this guidance will also encourage the development of appropriate data and facilitate their incorporation in a consistent fashion in dose-response assessment for regulatory purposes (IPCS, 2001).