In an advance in efforts Bruno Miguel Neves and colleagues at the University of Aveiro, are describing a new, highly accurate non-animal test for skin-sensitizers.
The sensitizing potential of chemicals is currently assessed using animal models. However, ethical and economic concerns and the recent European legislative framework triggered intensive research efforts in the development and validation of alternative methods.
Therefore, the aim of the study, published in the ACS' journal Chemical Research in Toxicology, was to develop an in vitro predictive test based on the analysis and integration of gene expression and intracellular signaling profiles of chemical-exposed skin-derived dendritic cells.
Neves explains that concerns about the ethics and costs of animal-based tests for skin sensitizers, plus regulations in the European Union, are fostering a search for alternative tests.
He says that testing product ingredients prior to marketing is important, because allergic contact dermatitis is the most prevalent form of immunotoxicity in humans.
The scientists describe development of a cell-based alternative test that enlists genes and signaling pathways in mouse skin cells growing in the laboratory.
Exposure to skin sensitizers triggers characteristic responses, activating genes and making cells release substances that communicate with adjacent cells.
Evaluation of the test on 18 compounds showed that it had a sensitivity of 92 percent in correctly identifying actual sensitizers. It had a specificity of 100 percent and did not produce any false positive results; indicating that a substance caused sensitization when, in fact, it did not.
The approach could be "extremely valuable" in revealing the interaction of skin cells with sensitizers, the scientists say.
The study was funded by Fundação para a Ciência e a Tecnologia (FCT), Fundo Comunitário Europeu (FEDER) and Programa Operacional Factores de Competitividade (COMPETE).
Bruno Miguel Neves, Susana Carvalho Rosa, João Demétrio Martins, Ana Silva, Margarida Gonçalo, Maria Celeste Lopes, Maria Teresa Cruz. Development of an in Vitro Dendritic Cell-Based Test for Skin Sensitizer Identification. Chemical Research in Toxicology, 2013; 26 (3): 368 DOI: 10.1021/tx300472d