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Genetic Toxicology Testing and its Relevance to Human Risk and Safety Evaluation

Genetic Toxicology, Oncogenesis, Developmental and Reproductive Toxicology

  1. Elisabeth Lorge MSc

Published Online: 15 DEC 2009

DOI: 10.1002/9780470744307.gat076

General, Applied and Systems Toxicology

General, Applied and Systems Toxicology

How to Cite

Lorge, E. 2009. Genetic Toxicology Testing and its Relevance to Human Risk and Safety Evaluation. General, Applied and Systems Toxicology. .

Author Information

  1. Drug Safety Assessment, Servier Group, 45403 Fleury-les-Aubrais, BP, France

Publication History

  1. Published Online: 15 DEC 2009

Abstract

Genotoxicity is a major concern in toxicity evaluation as it may cause carcinogenicity and/or genetic diseases. Therefore genotoxicity has become a part of the toxicity regulatory assessment. Over 30 years of practice in genotoxicity, various tests and tools have been developed, validated and refined. The protocols of the most currently used tests were improved and the experimental conditions were monitored more satisfactorily. In this chapter, the main genotoxicity tests required by the current International Conference on Harmonisation (ICH) battery are reviewed, as well as the most commonly used experimental systems added to the battery for follow-up testing, with their advantages and limits. The evaluation of genotoxicity results is also extensively considered. In this exercise, it is shown how the knowledge accumulated in the last years can be used to improve results evaluation with special references to the assessment and level of cytotoxicity, metabolic activation, aneuploidy, non-DNA reacting mutagens, thresholds and risk assessment.

Keywords:

  • genotoxicity;
  • genetic toxicology;
  • mutagenesis;
  • mutagen;
  • risk assessment;
  • toxicology