title: Non-animal photosafety assessment approaches for cosmetics based on the photochemical and photobiochemical properties.
abstract: The main purpose of the present study was to establish a non-animal photosafety assessment approach for cosmetics using in vitro photochemical and photobiochemical screening systems. Fifty-one cosmetics, pharmaceutics and other chemicals were selected as model chemicals on the basis of animal and/or clinical photosafety information. The model chemicals were assessed in terms of photochemical properties by UV/VIS spectral analysis, reactive oxygen species (ROS) assay and 3T3 neutral red uptake phototoxicity testing (3T3 NRU PT). Most phototoxins exhibited potent UV/VIS absorption with molar extinction coefficients of over 1000M(-1)cm(-1), although false-negative prediction occurred for 2 cosmetic phototoxins owing to weak UV/VIS absorption. Among all the cosmetic ingredients, ca. 42% of tested chemicals were non-testable in the ROS assay because of low water solubility; thereby, micellar ROS (mROS) assay using a solubilizing surfactant was employed for follow-up screening. Upon combination use of ROS and mROS assays, the individual specificity was 88.2%, and the positive and negative predictivities were estimated to be 94.4% and 100%, respectively. In the 3T3 NRU PT, 3 cosmetics and 4 drugs were incorrectly predicted not to be phototoxic, although some of them were typical photoallergens. Thus, these in vitro screening systems individually provide false predictions; however, a systematic tiered approach using these assays could provide reliable photosafety assessment without any false-negatives. The combined use of in vitro assays might enable simple and fast non-animal photosafety evaluation of cosmetic ingredients.
authors.affiliation: Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan. Electronic address: onoue@u-shizuoka-ken.ac.jp.
authors.forename: Satomi
authors.initials: S
authors.lastname: Onoue
authors.forename: Gen
authors.initials: G
authors.lastname: Suzuki
authors.forename: Masashi
authors.initials: M
authors.lastname: Kato
authors.forename: Morihiko
authors.initials: M
authors.lastname: Hirota
authors.forename: Hayato
authors.initials: H
authors.lastname: Nishida
authors.forename: Masato
authors.initials: M
authors.lastname: Kitagaki
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kouzuki
authors.forename: Shizuo
authors.initials: S
authors.lastname: Yamada
mesh_terms: D000826:Animal Testing Alternatives; D000818:Animals; D041702:BALB 3T3 Cells; D001681:Biological Assay; D003257:Consumer Product Safety; D003358:Cosmetics / Q000528:radiation effects / Q000633:toxicity*; D017484:Dermatitis, Phototoxic / Q000209:etiology; D051379:Mice; D009499:Neutral Red / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014466:Ultraviolet Rays
chemical_list: D003358:Cosmetics; D017382:Reactive Oxygen Species; D009499:Neutral Red
keywords: 3T3 NRU PT; 3T3 neutral red uptake phototoxicity testing; ANOVA; CMC; Cosmetics; DMSO; ECVAM; European Centre for the Validation of Alternative Methods; ICH; IFRA; International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use; International Fragrance Association; JPMA; JaCVAM; Japan Pharmaceutical Manufacturers Association; Japanese Center for the Validation of Alternative Methods; MEC; NBT; NaPB; OECD; Organisation for Economic Co-operation and Development; PIF; Photochemical property; Photosafety assessment; Phototoxicity; ROS; Reactive oxygen species; UV; VIS light; critical micelle concentration; dimethyl sulfoxide; mROS assay; micellar ROS assay; molar extinction coefficient; nitroblue tetrazolium; one-way analysis of variance; photo human cell line activation test; photo-h-CLAT; photoirritation factor; reactive oxygen species; sodium phosphate buffer; ultraviolet; visible light