Safety evaluation of natural flavour complexes

R. L. Smith, T. B. Adams, S. M. Cohen, J. Doull, V. J. Feron, J. I. Goodman, R. L. Hall, L. J. Marnett, P. S. Portoghese, W. J. Waddell, B. M. Wagner

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


Natural flavour complexes (NFCs) are chemical mixtures obtained by applying physical separation methods to botanical sources. Many NFCs are derived from foods. In the present paper, a 12-step procedure for the safety evaluation of NFCs, 'the naturals paradigm', is discussed. This procedure, which is not intended to be viewed as a rigid check list, begins with a description of the chemical composition of the commercial product, followed by a review of the data on the history of dietary use. Next, each constituent of an NFC is assigned to one of 33 congeneric groups of structurally related substances and to one of three classes of toxic potential, each with its own exposure threshold of toxicological concern. The group of substances of unknown structure is placed in the class of greatest toxic potential. In subsequent steps, for each congeneric group the procedure determines the per capita intake, considers metabolic pathways and explores the need and availability of toxicological data. Additional toxicological and analytical data may be required for a comprehensive safety evaluation. The procedure concludes with an evaluation of the NFC in its entirety, also considering combined exposure to congeneric groups. The first experiences with the use of this procedure are very promising. Future safety evaluations of larger numbers of NFCs will indicate the usefulness of the system, either in its present form or in a form modified on the basis of experience.

Original languageEnglish (US)
Pages (from-to)197-207
Number of pages11
JournalToxicology Letters
Issue number1-3
StatePublished - Apr 1 2004


  • Mixtures
  • Natural flavour complexes
  • Safety evaluation

ASJC Scopus subject areas

  • Toxicology


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