The safety evaluation of food flavoring substances: the role of genotoxicity studies

Nigel J. Gooderham, Samuel M. Cohen, Gerhard Eisenbrand, Shoji Fukushima, F. Peter Guengerich, Stephen S. Hecht, Ivonne M.C.M. Rietjens, Thomas J. Rosol, Maria Bastaki, Matthew J. Linman, Sean V. Taylor

Research output: Contribution to journalReview articlepeer-review

11 Scopus citations


The Flavor and Extract Manufacturers Association (FEMA) Expert Panel relies on the weight of evidence from all available data in the safety evaluation of flavoring substances. This process includes data from genotoxicity studies designed to assess the potential of a chemical agent to react with DNA or otherwise cause changes to DNA, either in vitro or in vivo. The Panel has reviewed a large number of in vitro and in vivo genotoxicity studies during the course of its ongoing safety evaluations of flavorings. The adherence of genotoxicity studies to standardized protocols and guidelines, the biological relevance of the results from those studies, and the human relevance of these studies are all important considerations in assessing whether the results raise specific concerns for genotoxic potential. The Panel evaluates genotoxicity studies not only for evidence of genotoxicity hazard, but also for the probability of risk to the consumer in the context of exposure from their use as flavoring substances. The majority of flavoring substances have given no indication of genotoxic potential in studies evaluated by the FEMA Expert Panel. Examples illustrating the assessment of genotoxicity data for flavoring substances and the consideration of the factors noted above are provided. The weight of evidence approach adopted by the FEMA Expert Panel leads to a rational assessment of risk associated with consumer intake of flavoring substances under the conditions of use.

Original languageEnglish (US)
Pages (from-to)1-27
Number of pages27
JournalCritical Reviews in Toxicology
Issue number1
StatePublished - Jan 2 2020

Bibliographical note

Funding Information:
This work was supported by the Flavor and Extract Manufacturers Association (FEMA), a US-based trade association comprised of member companies that manufacture and/or use food flavorings. The FEMA Expert Panel is a group of scientists qualified by training and experience to conduct scientifically independent evaluations of the safety of food flavoring substances. The FEMA Expert Panel is scientifically and procedurally independent but is financially supported by FEMA. The employment affiliation of each co-author is declared above, and each of these authors participated in the review process and preparation of this paper as independent professionals and not as a representative of his or her employer. The manuscript reflects the knowledge and judgment of the FEMA Expert Panel members as applied for the assessment of flavoring substances for GRAS status. The opinions expressed, and final conclusions set out in this overview paper were those of the listed authors and no one else.

Publisher Copyright:
© 2020, © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.


  • DNA adducts
  • chromosomal damage
  • flavoring substance
  • flavors
  • genotoxicity
  • mutagenicity
  • risk assessment
  • safety assessment
  • weight of evidence


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