THE LIVING DERMAL EQUIVALENT AS AN INVITRO MODEL FOR PREDICTING OCULAR IRRITATION

The Living Dermal Equivalent (LDE), composed of human dermal fibroblasts in a collagen-containing matrix, was used as a model system for examining toxic responses to a broad range of test chemicals and final product formulations. The thiazolyl blue (MTT) assay for mitochondrial function and the release of proinflammatory eicosanoids (prostaglandin E2 and prostacyclin) were used as end points to rank order the relative irritancy of test samples. In these studies a total of 65 test samples including liquids, creams, emulsions, and solids were applied topically to the air-exposed surface of the LDE. Protocols were designed to maximize the discrimination between samples with known ocular irritation potentials. For a given set of samples, altering the experimental conditions, including the dosage and time of exposure, is shown to influence the degree to which responses of the LDE agree with in vivo data. Strategies for using the LDE as an in vitro ocular irritation model are presented and recommendations for standardized protocols are discussed.