Use of human skin cell cultures for the estimation of potential skin irritants.

We have investigated the use of cell cultures derived from human skin (keratinocytes and fibroblasts) and of cultured SV40 transformed human keratinocytes (SVK14 cells) for in vitro screening for skin toxicity. To assess the cytotoxic effects of a number of surfactants the following cytotoxicity assays were performed: (1) changes in cell morphology and cell number in confluent cultures; (2) inhibition of cell proliferation; (3) modulation of interleukin-6 (IL-6) production. The data obtained in vitro were compared with the results of an in vivo study (Tupker et al. Contact Dermatitis 1989, 20, 108-114), in which visual scoring and measurement of transepidermal water loss were taken as measures of skin irritancy. The results of the morphological and proliferation studies in vitro indicated a similar ranking order in skin irritancy as that found in the in vivo study. Furthermore, IL-6 production by cultured skin cells was increased on administration of nearly all of the surfactants tested. For a number of surfactants the increase in IL-6 production occurred at much lower concentration than those necessary to induce cytotoxic effect, suggesting that monitoring the IL-6 production on administration of skin irritating agents could be used as a very sensitive test.