The silicon microphysiometer for testing ocular toxicity in vitro

Abstract

The silicon microphysiometer has been used for in vitro evaluation of the ocular irritancy potential of water soluble ingredients and formulations. This light-addressable potentiometric sensor detects changes in cell physiology by monitoring the rate at which cultured cells excrete their acidic products of metabolism. We have mainly determined the metabolic effect of 53 products (21 surfactants and 32 surfactant-based formulations). The related maximal average Draize score (MAS) were available from historical data and varied from 1.7 to 54. All of the Draize categories were represented. Murine fibroblastic cells (L929 clone) were exposed to increasing concentrations of the product for approximately 400 sec per dose. The MRD 50 (dose of product that decreased the metabolic rate of the cells by 50%) was determined by interpolation from a plot of metabolic rate versus test material concentration. Decreases in metabolic rate, as assessed by the MRD 50, occurred over a wide range of concentrations (40 μg/ml–200 mg/ml). The linear (Pearson) and rank (Spearman) correlation between in vivo (MAS) and in vitro (log MRD 50) data were 0.91 and 0.89, respectively. This study indicates that the silicon microphysiometer method exhibits a high correlation with the Draize test for water-soluble raw materials and formulations and thus can be used as an in vitro screen for ocular irritation.