Evaluation of genotoxicity of nitrile fragrance ingredients using in vitro and in vivo assays

• Published in: Food and chemical toxicology Vol. 59; pp. 784 - 792
• Main Authors: Bhatia, S.P., Politano, V.T., Api, A.M.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.09.2013; Elsevier
• Subjects: Ames test; Animals; Biological and medical sciences; Cell Line; chromosome aberrations; Cosmetics - administration & dosage; Cosmetics - chemistry; Cosmetics - toxicity; Cricetinae; Cricetulus; Domestic and cosmetic products toxicology; Dose-Response Relationship, Drug; Female; genotoxicity; Genotoxicity on fragrance materials; ingredients; Male; Medical sciences; Mice; Mice, Inbred Strains; Micronucleus Tests; Mutagenicity Tests; Mutation - drug effects; nitriles; Nitriles - administration & dosage; Nitriles - chemistry; Nitriles - toxicity; Odorants; odors; Salmonella typhimurium - drug effects; Salmonella typhimurium - metabolism; Toxicity Tests, Acute; Toxicology; Volatilization; Genotoxicity on fragrance materials; Cosmetic; Assay; Evaluation; In vivo; Nitrile; Toxicity; Perfume; Genotoxicity; In vitro
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2013.04.040

•Genotoxicity tests were conducted on eight nitriles used as fragrance materials.•No mutagenicity was observed in Ames tests (+S9) conducted in seven nitriles.•Nitriles positive in in vitro CA and in vitro MNT were also tested in in vivo MMNT.•No mutagenicity was noted in in vivo MMNT (high dose ranged 200 to 2000mg/kg/day).•It is concluded that these eight nitriles are not considered to be genotoxic Genotoxicity studies were conducted on a group of 8 fragrance ingredients that belong to the nitrile family. These nitriles are widely used in consumer products however there is very limited data in the literature regarding the genotoxicity of these nitriles. The 8 nitriles were assessed for genotoxicity using an Ames test, in vitro chromosome aberration test or in vitro micronucleus test. The positive results observed in the in vitro tests were further investigated using an in vivo micronucleus test. The results from these different tests were compared and these 8 nitriles are not considered to be genotoxic. Dodecanitrile and 2,2,3-trimethylcyclopent-3-enylacetonitrile were negative in the in vitro chromosome aberration test and in vitro micronucleus test, respectively. While citronellyl nitrile, 3-methyl-5-phenylpentanenitrile, cinnamyl nitrile, and 3-methyl-5-phenylpent-2-enenitrile revealed positive results in the in vitro tests, but confirmatory in vivo tests determined these nitriles to be negative in the in vivo micronucleus assay. The remaining two nitriles (benzonitrile and α-cyclohexylidene benzeneacetonitrile) were negative in the in vivo micronucleus test. This study aims to evaluate the genotoxicity potential of these nitriles as well as enrich the literature with genotoxicity data on fragrance ingredients.