Comparative overview of current international strategies and guidelines for genetic toxicology testing for regulatory purposes
- 1 June 2006
- journal article
- research article
- Published by Wiley in Environmental and Molecular Mutagenesis
- Vol. 47 (5), 362-390
- https://doi.org/10.1002/em.20216
Abstract
National and international regulatory agencies historically have used genotoxicity information as part of a weight‐of‐evidence approach to evaluate potential human carcinogenicity. Additionally, some agencies consider heritable mutation a regulatory endpoint. Furthermore, genotoxicity has the potential to contribute to other adverse health conditions. This article provides a comparative overview of the testing strategies used by regulatory agencies throughout the world. Despite minor variations in details, the genotoxicity test schemes for most regulatory entities generally comprise three tests: a bacterial gene mutation assay, an in vitro mammalian cell assay for gene mutation and/or chromosome aberrations, and often an in vivo assay for chromosomal effects. In some cases, fewer than these three tests are required. In other cases, when exposure data, structure‐activity considerations, or other factors warrant, even chemicals negative in the three baseline tests may be subject to additional testing. If genotoxicity is identified by the baseline screening tests, assessment of the ability of the chemical to interact with DNA in the gonad may be required. This may apply regardless of whether or not a cancer bioassay has been triggered. Mutagens positive in second stage gonadal assay(s) may be tested in third stage in vivo rodent tests to provide data for a quantitative risk assessment. In all testing, theutilization of internationally‐recognized protocols, where they exist, is advisable, although not in all instances required. When testing for regulatory purposes, it is advisable to verify the testing program with the specific regulatory body or bodies responsible forregulatory oversight before beginning testing. Environ. Mol. Mutagen., 2006. Published 2006 Wiley‐Liss, Inc.Keywords
This publication has 20 references indexed in Scilit:
- Use of genetic toxicology information for risk assessmentEnvironmental and Molecular Mutagenesis, 2005
- Use of Genotoxicity Data to Support Clinical Trials or Positive Genetox Findings on a Candidate Pharmaceutical or Impurity …. Now What?International Journal of Toxicology, 2005
- Genotoxicity risk assessment: a proposed classification strategyMutation Research - Genetic Toxicology and Environmental Mutagenesis, 2002
- New OECD Genetic Toxicology Guidelines and Interpretation of ResultsPublished by Informa UK Limited ,2001
- Carcinogenicity Testing and the Evaluation of Regulatory Requirements for PharmaceuticalsRegulatory Toxicology and Pharmacology, 1997
- Acrylamide: a review of its genotoxicity and an assessment of heritable genetic riskMutation Research, 1995
- Assessing the risk of heritable gene mutation in mammals: Drosophila sex-linked recessive lethal test and tests measuring DNA damage and repair in mammalian germ cellsEnvironmental and Molecular Mutagenesis, 1994
- Considerations in the U.S. Environmental Protection Agency's testing approach for mutagenicityMutation Research/Reviews in Genetic Toxicology, 1991
- Guidelines on the use of mutagenicity tests in the toxicological evaluation of chemicalsEnvironmental and Molecular Mutagenesis, 1988
- Principles of Genetic ToxicologyPublished by Springer Science and Business Media LLC ,1987