Thornback-LeCoq, S. J.-M. Bettems, and J. A. Zijlstra. Correlation between Skin Irritation and Cytotoxicity. In Vitro Toxicol. 1997. 10(1): 49-53.

We are currently validating the use of cytotoxicity tests for predicting the possible skin irritating potential of various topical formulations. The cytotoxicity is determined in fibroblast cultures using the neutral red release (NRR) assay and the MTT test. For most products, the MTT test is more sensitive and detects cytotoxic effects at lower concentrations than the NRR test.

The results of the cytotoxicity tests show a good correlation with the skin irritation potential, which we measure on hairless guinea pigs. In general, a product is unlikely to be irritating if the IC₅₀ is higher than 250 mg/ml in the NRR test, or higher than 125 mg/ml in the MTT assay, after 5 min exposure. The overall correlation between the cytotoxicity test and the skin irritation potential is good (r² = 0.77 for 49 formulations tested).

We found the cytotoxicity tests most useful as an aid for selecting the most promising among a series of similar formulations, thus significantly reducing the number of animal experiments. They can also be used for identifying the causative agent in an irritating complex mixture.