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Development of a multiparametric in vitro model of skin sensitization.
- Source :
-
Journal of applied toxicology : JAT [J Appl Toxicol] 2015 Jan; Vol. 35 (1), pp. 48-58. Date of Electronic Publication: 2014 Feb 03. - Publication Year :
- 2015
-
Abstract
- Most animal experiments on cosmetics safety are prohibited and since March 2013, this obligation includes sensitization tests. However, until now there has been no validated alternative in vitro method. In this work, 400 compounds used in the cosmetic industry were selected to cover the greatest diversity of structures, biological activities and sensitizing potential. These molecules were submitted to a series of tests aimed at reproducing essential steps in sensitization and to distinguish between sensitization and irritations, i.e., transcutaneous permeation (factor A), haptenation (factor B), sensitization cytokines production (factor C) and acute toxicity (factor D). The transcutaneous diffusion was measured on human skin explants using Franz cells. Haptenation was tested in solution on human serum albumin. Sensitization cytokine production was investigated by measurement of interleukin-18 release by keratinocytes. Acute toxicity was determined using an 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(75) cell viability test. As only sufficiently stable, soluble and detectable compounds are usable, 33, 72, 68 and 68 molecules were finally tested on factors A, B, C and D, respectively, and 32 were completely screened by the four factors. The individual correlation of the four factors with the reference in vivo tests was limited but the combination of these factors led to a correlation between in vivo and in vitro assays of 81.2% and the safety of the test (risk of false negative) reached 96.8%. The techniques employed are simple and inexpensive and this model of four tests appears as a promising technique to evaluate in vitro the skin sensitization potential of unknown molecules.<br /> (Copyright © 2014 John Wiley & Sons, Ltd.)
- Subjects :
- Allergens chemistry
Animal Testing Alternatives
Cell Survival drug effects
Cells, Cultured
Cosmetics chemistry
Dermatitis, Allergic Contact immunology
Diffusion Chambers, Culture
Haptens metabolism
Humans
In Vitro Techniques
Interleukin-18 biosynthesis
Interleukin-18 immunology
Irritants chemistry
Irritants toxicity
Keratinocytes immunology
Keratinocytes pathology
Models, Statistical
Multivariate Analysis
Skin pathology
Skin Absorption drug effects
Toxicity Tests, Acute methods
Allergens toxicity
Cosmetics toxicity
Dermatitis, Allergic Contact etiology
Keratinocytes drug effects
Skin drug effects
Skin immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1099-1263
- Volume :
- 35
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of applied toxicology : JAT
- Publication Type :
- Academic Journal
- Accession number :
- 24496914
- Full Text :
- https://doi.org/10.1002/jat.2986