HUMAN KERATINOCYTE CULTURES IN AN IN-VITRO APPROACH FOR THE ASSESSMENT OF SURFACTANT-INDUCED IRRITATION

A specific, mechanistic, in vitro approach for the assessment of human skin irritation potential is outlined for the evaluation of surfactan ts and the results compared with in vivo human patch test data. The le vel of foe available surfactant monomer and the solubilization of the corn protein zein in vitro were confirmed to be related to surfactant in vivo human skin irritation potential. In vitro cytotoxicity to mono layer keratinocyte cultures could not discriminate between the moderat e human skin irritant sodium dodecyl sulfate (SDS) and the mild irrita nts cocamidopropylbetaine (CA) and Polysorbate 20 (P20). An in vitro s tratified differentiated human epidermal equivalent (HEE) exhibited re duced cytotoxicity to the rest chemicals, compared with monolayer cult ure responses, and was able to discriminate between the toxic potentia l of SDS and CA. Stimulation of interleukin-1 alpha release from the A 431 human keratinocyte cell line reflected in vivo erythema scores mor e closely than cytotoxic potential, and coincided with nitric oxide pr oduction by macrophages upon exposure to A431-conditioned medium. Comb ination of these mechanistic assays has allowed a profile of likely in vivo human responses to be approximated. Additional knowledge of skin penetrability and rate of recovery from toxic damage would affirm the se predictions. (C) 1998 Elsevier Science Ltd. All rights reserved.