Good cell culture practice and characterization of the cell lines used are of critical importance in in vitro genotoxicity testing. The objective of this initiative was to make continuously available stocks of the characterized isolates of the most frequently used mammalian cell lines in genotoxicity testing anywhere in the world (‘IVGT’ cell lines).
Genetic Toxicology (GTTC) Committee
Genetic Toxicology (GTTC) Committee
The mission of this technical committee is to improve the scientific basis of the interpretation of results from genetic toxicology tests for purposes of more accurate hazard identification and assessment of human risk; to develop follow-up strategies for determining the relevance of test results to human health; to provide a framework for integration of testing results into a risk-based assessment of the effects of chemical exposures on human health; to promote the integration and use of new techniques and scientific knowledge in the evaluation of genetic toxicology; and to monitor and promote the development of innovative test and testing strategies.
To enable the broader context for examining genetic damage, a next generation testing strategy needs to take into account a broader, more flexible approach to testing, and ultimately modeling, of genomic damage as it relates to human exposure. The outline of a flexible approach and associated considerations are presented in a series of nine steps, some of which can occur in parallel, which was developed through a collaborative effort by leading genetic toxicologists from academia, government, and industry through the International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) Genetic Toxicology Technical Committee (GTTC).
Applied genetic toxicology is undergoing a transition from qualitative hazard identification to quantitative dose–response analysis and risk assessment. To facilitate this change, the Health and Environmental Sciences Institute (HESI) Genetic Toxicology Technical Committee (GTTC) sponsored a workshop held in Lancaster, UK on July 10–11, 2014. The event included invited speakers from several institutions and the contents was divided into three themes—1: Point-of-departure Metrics for Quantitative Dose–Response Analysis in Genetic Toxicology; 2: Measurement and Estimation of Exposures for Better Extrapolation to Humans and 3: The Use of Quantitative Approaches in Genetic Toxicology for human health risk assessment (HHRA). A host of pertinent issues were discussed relating to the use of in vitro and in vivo dose–response data, the development of methods for in vitro to in vivo extrapolation and approaches to use in vivo dose–response data to determine human exposure limits for regulatory evaluations and decision-making. This Special Issue, which was inspired by the workshop, contains a series of papers that collectively address topics related to the aforementioned themes. The Issue includes contributions that collectively evaluate, describe and discuss in silico, in vitro, in vivo and statistical approaches that are facilitating the shift from qualitative hazard evaluation to quantitative risk assessment. The use and application of the benchmark dose approach was a central theme in many of the workshop presentations and discussions, and the Special Issue includes several contributions that outline novel applications for the analysis and interpretation of genetic toxicity data. Although the contents of the Special Issue constitutes an important step towards the adoption of quantitative methods for regulatory assessment of genetic toxicity, formal acceptance of quantitative methods for HHRA and regulatory decision-making will require consensus regarding the relationships between genetic damage and disease, and the concomitant ability to use genetic toxicity results per se.
The ICH S6(R1) recommendations on safety evaluation of biotherapeutics have led to uncertainty in determining what would constitute a cause for concern that would require genotoxicity testing.
In vitro genotoxicity assessment routinely employs an exogenous metabolic activation mixture to simulate mammalian metabolism.