Determination of skin irritation potential in the human 4-h patch test.

Recently adopted legislation in Europe has increased the focus that must be placed on the development of in vitro alternatives to the traditional toxicology tests employed to identify the human health hazards associated with chemicals. Included in these is the rabbit skin-irritation test which is used to discriminate those substances which possess significant acute skin irritation potential from those which are of more limited irritation potential. So far, the considerable efforts to replace this assay with in vitro alternatives have not been successful, which may in part be due to the relatively poor quality of the existing in vivo dataset. To help address this problem, we have elected to present our complete database of information on the skin irritation potential of some 65 substances, all of which have been tested in a standard human 4-h patch test. These provide a high quality dataset, generated in man (the goal of toxicologists' health protection-related activities). The data are presented in the context of results with a concurrent positive skin irritation control to ensure that results from individual experiments can be correlated. Consequently, in vitro or in silico alternatives which can identify the significant acute human skin irritants in this group may well represent suitable alternatives to the rabbit.