Applicability of in vitro tests for skin irritation and corrosion to regulatory classification schemes: substantiating test strategies with data from routine studies.

ABSTRACT

Skin corrosion or irritation refers to the production of irreversible or reversible damage to the skin following the application of a test substance, respectively. Traditionally, hazard assessments are conducted using the in vivo Draize skin test, but recently in vitro tests using reconstructed human epidermis (RhE) models have gained regulatory acceptance. In this study, skin corrosion (SCT) and irritation tests (SIT) using a RhE model were implemented to reduce the number of in vivo tests required by regulatory bodies. One hundred and thirty-four materials were tested from a wide range of substance classes included 46 agrochemical formulations. Results were assessed according to UN GHS, EU-CLP, ANVISA and US EPA classification schemes. There was high correlation between the two in vitro tests. Assessment of the SCT sensitivity was not possible due to the limited number of corrosives in the data set; SCT specificity and accuracy were 89% for all classification systems. Accuracy (63-76%) and sensitivity (53-67%) were low in the SIT. Specificity and concordance for agrochemical formulations alone in both the SCT and SIT were comparable to the values for the complete data set (SCT 91% vs. 89% specificity, 91% vs. 89% accuracy and SIT 64-88% vs. 70-85% specificity, 56-75% vs. 63-76% accuracy).