Safety evaluation of substituted thiophenes used as flavoring ingredients.
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.
Department of Pathology and Microbiology, University of Nebraska Medical Center, 983135 Nebraska Medical Center, Omaha, NE, 68198-3135, USA. Electronic address: scohen@unmc.edu.
Samuel M
SM
Cohen
Japan Bioassay Research Center, 2445 Hirasawa, Hadano, Kanagawa, 257-0015, Japan. Electronic address: s-fukushima@jisha.or.jp.
Shoji
S
Fukushima
Department of Surgery and Cancer, Imperial College of London, Sir Alexander Fleming Building, London, SW7 2AZ, United Kingdom. Electronic address: n.gooderham@imperial.ac.uk.
Nigel J
NJ
Gooderham
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, 37232-0146, USA. Electronic address: f.guengerich@vanderbilt.edu.
F Peter
FP
Guengerich
Wallin Professor of Cancer Prevention, Masonic Cancer Center and Department of Laboratory Medicine and Pathology, University of Minnesota, Cancer and Cardiovascular Research Building, 2231 6th St. SE, Minneapolis, MN, 55455, USA. Electronic address: hecht002@umn.edu.
Stephen S
SS
Hecht
Division of Toxicology, Wageningen University, Stippeneng 4, 6708 WE, Wageningen, The Netherlands. Electronic address: Ivonne.Rietjens@wur.nl.
Ivonne M C M
IM
Rietjens
Molecular Toxicology, Imperial College School of Medicine, Sir Alexander Fleming Building, London, SW7 2AZ, United Kingdom. Electronic address: rrlsmith@btinternet.com.
Robert L
RL
Smith
Flavor and Extract Manufacturers Association, 1101 17th Street, NW Suite 700, Washington, DC, 20036, USA. Electronic address: MBastaki@vertosolutions.net.
Maria
M
Bastaki
Flavor and Extract Manufacturers Association, 1101 17th Street, NW Suite 700, Washington, DC, 20036, USA. Electronic address: charman@vertosolutions.net.
Christie L
CL
Harman
Flavor and Extract Manufacturers Association, 1101 17th Street, NW Suite 700, Washington, DC, 20036, USA. Electronic address: MMcGowen@vertosolutions.net.
Margaret M
MM
McGowen
Flavor and Extract Manufacturers Association, 1101 17th Street, NW Suite 700, Washington, DC, 20036, USA. Electronic address: lvalerio@vertosolutions.net.
Luis G
LG
Valerio
Flavor and Extract Manufacturers Association, 1101 17th Street, NW Suite 700, Washington, DC, 20036, USA. Electronic address: staylor@vertosolutions.net.
Sean V
SV
Taylor
D003257:Consumer Product Safety; D005421:Flavoring Agents / Q000032:analysis / Q000592:standards / Q000633:toxicity*; D006801:Humans; D019055:No-Observed-Adverse-Effect Level; D013876:Thiophenes / Q000032:analysis / Q000592:standards / Q000633:toxicity*; D018675:Toxicity Tests / Q000379:methods; D014481:United States; D014486:United States Food and Drug Administration
D005421:Flavoring Agents; D013876:Thiophenes
FEMA GRAS; Flavoring ingredients; Thiophene