Differential effects of chemical irritants in rabbit and human skin organ cultures

The toxicity of well known irritants was investigated in rabbit and human skin organ cultures. Test chemicals were selected from various categories of irritants and included both water-soluble and water-insoluble compounds. Using a highly standardized protocol, test chemicals were applied topically at concentrations relevant to the in vivo situation. Toxicity was assessed by histomorphological examination, inhibition of conversion of the tetrazolium salt MTT, inhibition of epidermal cell proliferation and release of pro-inflammatory hydroxy fatty acids. Chemicals that are known to induce irritation in vivo invariably caused histopathological changes and inhibition of cell proliferation, whereas non-irritating chemicals did not; however, inhibition of MTT conversion and release of hydroxy fatty acids occurred with only a limited number of irritants. The response to the chemical irritants was different in rabbit and human skin cultures. Rabbit skin was slightly more sensitive to sodium dodecyl sulfate and benzalkonium chloride than human skin. Moreover, mineral oil enhanced epidermal cell proliferation in rabbit skin, but not in human skin. This study demonstrates that chemical irritants cause substance- and species-specific effects in skin organ cultures. It is therefore unlikely that irritant potential of chemicals from all irritant categories can be detected in vitro using one single parameter. A multiple endpoint approach and the inclusion of human tissue are recommended for optimal in vitro irritancy testing of chemicals.