Evaluation of the test method for skin irritation as prescribed by oecd and EEC

Abstract

In this study solvents belonging to seven different chemical families were tested for their irritant properties to the skin. The chemical families considered are alicyclic, aliphatic, and aromatic hydrocarbons; brominated and chlorinated aliphatic hydrocarbons; alcohols; and aldehydes. The test protocol used is that described in the Annex V of the EEC Directive 79/831/EEC. The substances were applied to the shaved skin of rabbits by means of a chamber for 4 hr, after which the exposure chamber was removed and the skin cleaned. Reading of erythema and edema was performed according to the scale of Draize at 1, 24, 48, and 72 hr after removal of the patch. Thereafter the animals were observed every 2 days until complete healing of the skin had occurred in at least one rabbit. On the basis of the readings obtained the substances tested were classified as irritant or not according to the interpretation rules laid down in EEC Directive 83/467/EEC. Twelve test methods with different sets of observation times were evaluated against the EEC method. In this study 22 of the 30 substances and dilutions showed a tmax later than 72 hr, the time limit taken into account by the EEC for the evaluation and hence classification of skin irritants. The mean of the times of maximum erythema for all the substances tested is situated around 88 hr after the start of application. Simply shifting the observation period by 24 hr (from 24, 48, and 72 hr to 48, 72, and 96 hr) results in 20% more substances that will be classified as skin irritants. Highly irritating substances showing a late erythema peak (tmax > 72 hr) are particularly underestimated by the EEC method as to their potential to cause erythema. Edema cannot be characterized sufficiently well using the EEC method in its very early development.