Genotoxicity assessment of the flavouring agent, perillaldehyde.
Perillaldehyde, a natural monocyclic terpenoid found most abundantly in the herb perilla, has a long history of use as a flavouring ingredient to add spiciness and citrus taste to foods. Previously, it was judged to be safe by several international expert panels. To confirm the safety of flavourings placed on the European Union list of flavourings, perillaldehyde was selected by the European Food Safety Authority as a representative of a subgroup of alicyclic aldehyde flavouring substances to be evaluated for genotoxic potential. Perillaldehyde was tested in a bacterial reverse mutation assay, an in vitro micronucleus assay in human lymphocytes, an HPRT assay in mouse lymphoma cells, and a micronucleus/comet assay in Han Wistar rats. In contrast to previously published results, perillaldehyde induced mutation in Salmonella typhimurium strain TA98 in the absence of metabolic activation. The comet assay was negative for duodenum and weakly positive for liver but only at a hepatotoxic dose of perillaldehyde. All other genotoxicity assays were negative. These data do not provide an indication of any genotoxic potential for perillaldehyde, and they provide the primary basis for recent scientific opinions regarding perillaldehyde genotoxicity announced by several international organizations responsible for safety assessment of food additives and flavourings.
Toxicology Program, Integrated Laboratory Systems, Inc., PO Box 13501, Research Triangle Park, NC 27709, USA. Electronic address: chobbs@ils-inc.com.
Cheryl A
CA
Hobbs
International Organization of the Flavor Industry, 1101 17th Street NW, Suite 700, Washington, DC 20036, USA.
Sean V
SV
Taylor
Covance Laboratories Ltd, Otley Road, Harrogate, North Yorkshire, HG3 1PY, England, UK.
Carol
C
Beevers
Covance Laboratories Ltd, Otley Road, Harrogate, North Yorkshire, HG3 1PY, England, UK.
Melvyn
M
Lloyd
Covance Laboratories Ltd, Otley Road, Harrogate, North Yorkshire, HG3 1PY, England, UK.
Rachael
R
Bowen
Covance Laboratories Ltd, Otley Road, Harrogate, North Yorkshire, HG3 1PY, England, UK.
Lucinda
L
Lillford
Maronpot Consulting LLC, 1612 Medfield Road, Raleigh, NC 27607, USA.
Robert
R
Maronpot
Japan Flavor and Fragrance Materials Association, Sankei Nihonbashi Bldg 6F, 4-7-1 Nihonbashihon-cho, Chuo-ku, Tokyo, 103-0023, Japan.
Shim-Mo
SM
Hayashi
D000818:Animals; D002478:Cells, Cultured; D020552:Comet Assay / Q000379:methods; D004249:DNA Damage / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008214:Lymphocytes / Q000187:drug effects / Q000473:pathology*; D008223:Lymphoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D051379:Mice; D015162:Micronucleus Tests / Q000379:methods; D039821:Monoterpenes / Q000633:toxicity*; D009152:Mutagenicity Tests / Q000379:methods; D009154:Mutation / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D012486:Salmonella typhimurium
D039821:Monoterpenes; C033342:perillaldehyde
DNA damage; Flavouring agent; Genotoxicity; Perilla aldehyde; Perillaldehyde; p-mentha-1,8-dien-7-al