In vitro irritation models and immune reactions.
Irritant contact dermatitis is the result of an innate inflammatory response of the skin to direct injury. It is caused by a single, repeated or continued application of an irritant, with the source most often being a chemical. Therefore, European regulations require strict screening of all ingredients in consumer products. Until recently, identifying a potential irritant has completely relied on animal testing (for example, Draize test). Besides the ethical problems, both the 7th Amendment to the Cosmetics Directive and Registration, Evaluation and Authorization of Chemicals legislation have stimulated the development of alternative tests for the assessment of potential toxicological effects of substances. This review is aimed at describing current in vitro skin irritation models and the biomarkers used to assess the degree of irritancy of a potential irritant. Four models are described: keratinocyte and fibroblast cultures grown under submerged culture conditions, epidermal equivalents, skin equivalents and freshly isolated skin. Biomarkers such as IL-1alpha, IL-6, IL-8, PGE2, SKALP, HSP70 and kinases are described along with changes in metabolic activity (MTT assay) and cytosolic leakage (lactate dehydrogenase assay). Noticeable is the limited number of genomic and proteomic studies. Such studies have the potential to identify novel biomarkers and to elucidate the mechanism of irritant contact dermatitis.
Gibbs
S
S
VU University Medical Centre, Amsterdam, The Netherlands. S.Gibbs@vumc.nl
D000826:Animal Testing Alternatives / Q000331:legislation & jurisprudence; D000818:Animals; D015415:Biomarkers; D003257:Consumer Product Safety / Q000331:legislation & jurisprudence; D017453:Dermatitis, Irritant / Q000209:etiology* / Q000276:immunology; D005060:Europe; D006801:Humans; D007509:Irritants / Q000633:toxicity; D008954:Models, Biological; D012867:Skin / Q000187:drug effects* / Q000473:pathology; D023422:Skin Irritancy Tests / Q000379:methods*
D015415:Biomarkers; D007509:Irritants