IWGT report on quantitative approaches to genotoxicity risk assessment II. Use of point-of-departure (PoD) metrics in defining acceptable exposure limits and assessing human risk

• DOI: 10.1016/j.mrgentox.2014.10.008
• Publication Date: 2014-10-27T08:20:31Z
• Authors: James T. MacGregor; Roland Frötschl; Paul A. White; Kenny S. Crump; David A. Eastmond; Shoji Fukushima; Melanie Guérard; Makoto Hayashi; Lya G. Soeteman-H...; George E. Johnson; Toshio Kasamatsu; Dan D. Levy; Takeshi Morita; Lutz Müller; Rita Schoeny; Maik J. Schuler; Véronique Thybaud
• Keywords: Endpoint Determination

This is the second of two reports from International Workshops on Genotoxicity Testing (IWGT) Working Group Quantitative Approaches to Genetic Toxicology Risk Assessment (the QWG). The first report summarized discussions and recommendations QWG related need for quantitative dose-response analysis genetic toxicology data, existence appropriate evaluation threshold responses, methods analyze exposure-response relationships derive points departure (PoDs) which acceptable exposure levels could be determined. summarizes regarding approaches evaluate exposure-related risks genotoxic damage, including extrapolation below identified PoDs across test systems species. Recommendations include selection endpoints target tissues, uncertainty factors considered, importance use information mode action, toxicokinetics, metabolism, biomarkers when using data determine in human populations or assess risk associated with known anticipated exposures. empirical relationship between damage (mutation chromosomal aberration) cancer animal models was also examined. It concluded that there a general correlation induction mutagenic and/or clastogenic agents thought act via mechanism, but limited due an inadequate number cases mutation can compared at sufficient doses same tissues species strain exposed under directly comparable routes experimental protocols.