Need and potential value of the Pig-ain vivo mutation assay-a HESI perspective.

The Health and Environmental Sciences Institute (HESI), a global branch of the International Life Sciences Institute (ILSI), initiated a project committee entitled "Relevance and Follow-up of Positive Results from In Vitro Genetic Toxicity Testing (IVGT)" with the overall objective of improving the scientific basis for the interpretation of results from genetic toxicology testing. The IVGT committee has also recognized the need to develop follow-up strategies for determining the relevance of in vitro test results to human health, and moving genetic toxicology testing from the sole purpose of hazard identification toward a more quantitative risk assessment approach. In this context, a group of experts evaluated the potential utility of the emerging in vivo mutational assessment model commonly known as the Pig-a gene mutation assay to follow-up positive in vitro genetic toxicology findings and to generate robust dose-response data for quantitative assessment of the in vivo mutagenicity. The IVGT experts participating in this effort represented academia, industry, and government agencies from across the globe and addressed such issues as the optimal sample size and experimental design for generating robust dose-response data. This expert group concluded that the emerging Pig-a gene mutation assay holds great promise as an in vivo mutagenicity assay, either as a stand-alone study or integrated into repeat-dose toxicology studies, and therefore supports further validation of the model.