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Strategies and testing methods for identifying mutagenic risks

J T MacGregor1, D Casciano, L Müller

  • 1FDA Center for Drug Evaluation and Research, 5600 Fishers Lane, Rockville, MD 20857, USA. macgregorj@cder.fda.gov

Mutation Research
|December 13, 2000
PubMed

Insights

This review traces the history of mutagenicity testing, from early concerns to current harmonization efforts. Future directions include quantitative risk assessment and improved predictive models for mutagenic agents.

Area of Science:

  • Toxicology
  • Genetics
  • Risk Assessment

Background:

  • Concerns regarding chemical mutagens' health effects emerged in the 1940s.
  • Regulatory guidelines for mutagenicity testing were established in the 1970s and 1980s.
  • International harmonization of testing guidelines is an ongoing effort.

Purpose of the Study:

  • To discuss the evolution of mutagenicity testing strategies and methods.
  • To summarize efforts toward international harmonization of testing guidelines.
  • To identify current issues and future needs in mutagenicity testing.

Main Methods:

  • Historical review of mutagenicity testing development.
  • Summary of international harmonization initiatives.
  • Discussion of current challenges and future research directions.

Main Results:

  • The field has progressed from basic identification to complex risk assessment.
  • Key issues include quantitative risk assessment, dose-response, indirect mechanisms, and predictivity for carcinogenicity.
  • Future trends involve updated test batteries and advanced methods like gene expression profiling.

Conclusions:

  • Mutagenicity testing has evolved significantly, driven by health concerns and regulatory needs.
  • Further research is needed for quantitative risk assessment and improved predictive models.
  • The future of testing involves integrating new technologies and species-specific metabolic models.

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