Safety evaluation of substituted thiophenes used as flavoring ingredients

Samuel Monroe Cohen, Shoji Fukushima, Nigel J. Gooderham, F. Peter Guengerich, Stephen S. Hecht, Ivonne M C M Rietjens, Robert L. Smith, Maria Bastaki, Christie L. Harman, Margaret M. McGowen, Luis G. Valerio, Sean V. Taylor

Research output: Contribution to journalReview article

8 Citations (Scopus)

Abstract

This publication is the second in a series by the Expert Panel of the Flavor and Extract Manufacturers Association summarizing the conclusions of its third systematic re-evaluation of the safety of flavorings previously considered to be generally recognized as safe (GRAS) under conditions of intended use. Re-evaluation of GRAS status for flavorings is based on updated considerations of exposure, structural analogy, metabolism, pharmacokinetics and toxicology and includes a comprehensive review of the scientific information on the flavorings and structurally related substances. Of the 12 substituted thiophenes reviewed here, 11 were reaffirmed as GRAS based on their rapid absorption, metabolism and excretion in humans and animals; the low estimated dietary exposure from flavor use; the wide margins of safety between the conservative estimates of intake and the no-observed-adverse effect levels; and the lack of significant genotoxic and mutagenic potential. For one of the substituted thiophenes, 3-acetyl-2,5-dimethylthiophene, it was concluded that more detailed exposure information, comparative metabolism studies and comprehensive toxicity data, including an in-depth evaluation of the mechanism of action for any adverse effects observed, are required for continuation of its FEMA GRAS™ status. In the absence of these data, the compound was removed from the FEMA GRAS list.

Original languageEnglish (US)
Pages (from-to)40-59
Number of pages20
JournalFood and Chemical Toxicology
Volume99
DOIs
StatePublished - Jan 1 2017

Fingerprint

thiophenes
Thiophenes
flavorings
Metabolism
ingredients
Flavors
Safety
metabolism
GRAS substances
flavor
No-Observed-Adverse-Effect Level
no observed adverse effect level
margin of safety
Pharmacokinetics
dietary exposure
toxicology
Toxicology
pharmacokinetics
Toxicity
mechanism of action

Keywords

  • FEMA GRAS
  • Flavoring ingredients
  • Thiophene

ASJC Scopus subject areas

  • Food Science
  • Toxicology

Cite this

Cohen, S. M., Fukushima, S., Gooderham, N. J., Guengerich, F. P., Hecht, S. S., Rietjens, I. M. C. M., ... Taylor, S. V. (2017). Safety evaluation of substituted thiophenes used as flavoring ingredients. Food and Chemical Toxicology, 99, 40-59. https://doi.org/10.1016/j.fct.2016.10.023

Safety evaluation of substituted thiophenes used as flavoring ingredients. / Cohen, Samuel Monroe; Fukushima, Shoji; Gooderham, Nigel J.; Guengerich, F. Peter; Hecht, Stephen S.; Rietjens, Ivonne M C M; Smith, Robert L.; Bastaki, Maria; Harman, Christie L.; McGowen, Margaret M.; Valerio, Luis G.; Taylor, Sean V.

In: Food and Chemical Toxicology, Vol. 99, 01.01.2017, p. 40-59.

Research output: Contribution to journalReview article

Cohen, SM, Fukushima, S, Gooderham, NJ, Guengerich, FP, Hecht, SS, Rietjens, IMCM, Smith, RL, Bastaki, M, Harman, CL, McGowen, MM, Valerio, LG & Taylor, SV 2017, 'Safety evaluation of substituted thiophenes used as flavoring ingredients', Food and Chemical Toxicology, vol. 99, pp. 40-59. https://doi.org/10.1016/j.fct.2016.10.023
Cohen SM, Fukushima S, Gooderham NJ, Guengerich FP, Hecht SS, Rietjens IMCM et al. Safety evaluation of substituted thiophenes used as flavoring ingredients. Food and Chemical Toxicology. 2017 Jan 1;99:40-59. https://doi.org/10.1016/j.fct.2016.10.023
Cohen, Samuel Monroe ; Fukushima, Shoji ; Gooderham, Nigel J. ; Guengerich, F. Peter ; Hecht, Stephen S. ; Rietjens, Ivonne M C M ; Smith, Robert L. ; Bastaki, Maria ; Harman, Christie L. ; McGowen, Margaret M. ; Valerio, Luis G. ; Taylor, Sean V. / Safety evaluation of substituted thiophenes used as flavoring ingredients. In: Food and Chemical Toxicology. 2017 ; Vol. 99. pp. 40-59.
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