title: Retinyl palmitate is non-genotoxic in Chinese hamster ovary cells in the dark or after pre-irradiation or simultaneous irradiation with UV light.
abstract: Retinyl palmitate (RP), an ingredient of cosmetic and medical skin-care preparations, has been reported to be photo-genotoxic/photo-clastogenic in mouse lymphoma cells (Tk locus) as well as in human Jurkat T-cells, as measured by use of the comet assay. Given that these results were obtained under exploratory conditions, we re-investigated the photo-genotoxicity of RP following a protocol consistent with current recommendations for photo-genotoxicity testing of drugs and chemicals. We tested RP in Chinese hamster ovary (CHO) cells in the dark (standard chromosome aberration test), under pre-irradiation (UVA irradiation of cells and subsequent treatment with RP) or simultaneous irradiation (irradiation of cells and RP together, standard photo-genotoxicity protocol) conditions. UVA irradiation was applied at 350 and 700 mJ/cm2 with the high UV dose targeted to produce a small increase in the incidence of structural chromosome aberrations (CA) in cells not treated with RP. RP was tested up to and above its limit of solubility in the culture medium (20-40 μg/mL). There was no overt cytotoxicity under dark or different irradiation conditions. Treatment of cells with RP in the dark, as well as treatment under pre- or simultaneous irradiation conditions failed to produce biologically significant increases in the incidence of CA, whereas the positive control substances 4-nitroquinolone and 8-methoxypsoralene produced significantly positive effects in the dark or under simultaneous irradiation, respectively. Overall, our results failed to confirm the reported positive photo-genotoxic effects, and suggest that they may have been due to the test conditions, i.e. high irradiation doses, high cytotoxicity or re-irradiation of photo-products. In conclusion, our data suggest that, under standard conditions for testing photo-genotoxicity, RP had no in vitro genotoxic or photo-genotoxic potential and is therefore unlikely to pose a local or systemic genotoxic or photo-genotoxic risk.
authors.affiliation: L'Oréal Research and Development, Global Safety Department, 92600 Asnières, France.
authors.forename: Eric K
authors.initials: EK
authors.lastname: Dufour
authors.forename: James
authors.initials: J
authors.lastname: Whitwell
authors.forename: Gerhard J
authors.initials: GJ
authors.lastname: Nohynek
authors.forename: David
authors.initials: D
authors.lastname: Kirkland
authors.forename: Hervé
authors.initials: H
authors.lastname: Toutain
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D016466:CHO Cells / Q000187:drug effects* / Q000528:radiation effects*; D002869:Chromosome Aberrations; D020552:Comet Assay / Q000379:methods; D006224:Cricetinae; D004249:DNA Damage; D004224:Diterpenes; D006801:Humans; D019169:Jurkat Cells; D008027:Light; D008730:Methoxsalen / Q000494:pharmacology; D051379:Mice; D009152:Mutagenicity Tests / Q000379:methods*; D009153:Mutagens / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology; D000084562:Retinyl Esters; D014466:Ultraviolet Rays; D014801:Vitamin A / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D004224:Diterpenes; D009153:Mutagens; D015363:Quinolones; D000084562:Retinyl Esters; D014801:Vitamin A; C014794:retinol palmitate; D008730:Methoxsalen