title: FEMA expert panel review of p-mentha-1,8-dien-7-al genotoxicity testing results.
abstract: p-Mentha-1,8-dien-7-al is a naturally occurring cyclic alpha,beta-unsaturated aldehyde that is used as a flavoring substance throughout the world. Due to the chemical structure and the potential DNA reactivity of the alpha,beta-unsaturated carbonyl moiety, a battery of genotoxicity assays was requested by the European Food Safety Authority. Previous genotoxicity studies on the substance gave mixed results, but both positive and negative results were hampered by not always being performed to any standard guideline. The new test battery data indicated some evidence of mutagenicity in vitro, but an in vivo comet/micronucleus combination assay performed in rats was concluded by the study directors to not result in any biologically relevant positive responses. However, EFSA concluded that the in vivo assay gave evidence that p-mentha-1,8-dien-7-al was of potential genotoxic concern. The Expert Panel of the Flavor and Extract Manufacturers Association (FEMA) has reviewed the newly available data and considered its interpretation relative to standard guidelines such as that established by the Organization for Economic Cooperation and Development, and has concluded that the results in the comet/micronucleus combination assay are consistent with the interpretation by the study directors; namely, that p-mentha-1,8-dien-7-al does not appear to have any in vivo genotoxic potential.
authors: Dept. of Pathology and Microbiology, University of Nebraska Medical Center, 983135 Nebraska Medical Center, Omaha, NE 68198-3135, USA. Electronic address: scohen@unmc.edu.
authors: Samuel M
authors: SM
authors: Cohen
authors: Japan Bioassay Research Center, 2445 Hirasawa, Hadano, Kanagawa 257-0015, Japan. Electronic address: 2940-shoji@kxb.biglobe.ne.jp.
authors: Shoji
authors: S
authors: Fukushima
authors: Dept. of Surgery and Cancer, Imperial College of London, Sir Alexander Fleming Building, London, SW7 2AZ, United Kingdom. Electronic address: n.gooderham@imperial.ac.uk.
authors: Nigel J
authors: NJ
authors: Gooderham
authors: Dept. of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232-0146, USA. Electronic address: f.guengerich@vanderbilt.edu.
authors: F Peter
authors: FP
authors: Guengerich
authors: Wallin Professor of Cancer Prevention, Masonic Cancer Center and Dept. 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.
authors: Stephen S
authors: SS
authors: Hecht
authors: Division of Toxicology, Wageningen University, Stippeneng 4, 6708 WE, Wageningen, The Netherlands. Electronic address: ivonne.rietjens@wur.nl.
authors: Ivonne M C M
authors: IMCM
authors: Rietjens
authors: Molecular Toxicology, Imperial College School of Medicine, Sir Alexander Fleming Building, London, SW7 2AZ, United Kingdom. Electronic address: rrlsmith@btinternet.com.
authors: Robert L
authors: RL
authors: Smith
authors: Flavor and Extract Manufacturers Association, 1101 17th Street, NW Suite 700, Washington, DC 20036, USA. Electronic address: mbastaki@vertosolutions.net.
authors: Maria
authors: M
authors: Bastaki
authors: Flavor and Extract Manufacturers Association, 1101 17th Street, NW Suite 700, Washington, DC 20036, USA. Electronic address: charman@vertosolutions.net.
authors: Christie L
authors: CL
authors: Harman
authors: Flavor and Extract Manufacturers Association, 1101 17th Street, NW Suite 700, Washington, DC 20036, USA. Electronic address: mmcgowen@vertosolutions.net.
authors: Margaret M
authors: MM
authors: McGowen
authors: Flavor and Extract Manufacturers Association, 1101 17th Street, NW Suite 700, Washington, DC 20036, USA. Electronic address: staylor@vertosolutions.net.
authors: Sean V
authors: SV
authors: Taylor
mesh_terms: D000818:Animals; D004249:DNA Damage / Q000187:drug effects*; D007881:Legislation, Food / Q000639:trends*; D015162:Micronucleus Tests; D039821:Monoterpenes / Q000633:toxicity*; D009152:Mutagenicity Tests; D031343:Perilla / Q000737:chemistry*; D051381:Rats
chemical_list: D039821:Monoterpenes; C033342:perillaldehyde
keywords: FEMA GRAS; Flavoring ingredients; Genotoxicity; Perilla; Perillaldehyde