An in vivo-in vitro study of the use of a human skin equivalent for irritancy screening of fatty acids

A human skin equivalent (HSE) consisting of reconstructed epidermis on a fibroblast-populated collagen gel was evaluated as a model for irritancy screening. The irritancy potential of series of saturated and unsaturated fatty acids was investigated in vivo under short-term exposure conditions using transepidermal water loss (TEWL), laser Doppler velocimetry (LDV) and the penetration of hexyl nicotinate as parameters. The effects of the fatty acids in vitro were studied after topical application on HSE using changes in epidermal morphology, changes in interleukin (IL)-1 and interleukin-8 mRNA expression and protein levels, and alterations in activity of plasminogen activators as endpoints. The unsaturated fatty acids increased both TEWL and LDV and elevated IL-1 and IL-8 mRNA levels, whereas their effects on protein levels were minimal. In contrast, the saturated fatty acids were not very effective in vivo but induced an increase in IL-1 protein levels. The type of fatty acid determines not only the way and the extent of skin barrier modulation, but also the pattern of cell mediator production and release. This study stresses the neccessity of investigating multiple endpoints for the characterization of a test compound, in particular when studying mild and moderate irritants.