One area of interest in toxicological research is the development of in vitro model systems for in vivo human skin irritancy and allergenicity. The ability to distinguish between irritant and allergic contact dermatitis can lead to safer chemical formulations as well as improved treatment regimes for people who suffer from these conditions. Human health risk can also be better assessed by correlating the results of in vitro assays to other known endpoints of toxicity in vivo. The long-term objective of this proposal is to develop and validate an in vitro toxicologic assay in human skin cells. This assay will be designed to provide objective, quantifiable means for determining the irritancy or inflammatory potential of a substance, by measuring multiple interrelated endpoints of toxicity. The specific aims of the proposal encompass selecting and optimizing a cell line, developing the stress gene fusion constructs, developing stable recombinant keratinocyte lines and incorporating them into the assay, and validating the assay system. The data that are collected from this assay can be used to generate specific profiles of gene induction in response to toxic insult and will provide powerful information about the level and mechanisms of toxicity. The resultant gene induction profiles will generate new insights into the similarities and differences between irritant contact dermatitis and allergic contact dermatitis.Proposed commercial application:The keratinocyte stress gene assay can provide novel mechanistic information on compounds of interest to the pharmaceutical, cosmetics, chemical and environmental industries. This will reduce the need for whole animal testing and thus reduce the costs of bringing novel chemicals and formulations to market.National Institute of Arthritis and Muscoloskeletal and Skin Diseases (NIAMS)
