Dose-response for predicting skin sensitization potency with the GARD®skin method

Abstract: Allergic contacts dermatitis is a major health problem in the world and the disease is caused by a type IV hypersensitivity to a small chemical called a hapten. These substances are common in cosmetics, perfumes, pharmaceuticals and house-hold products, and risk factors include both inherent factors and frequent or high exposure. Hazard assessment and potency classification of sensitizers are thereby of great need, to enable withdrawal of problematic substances or decide on a dose with minimal adverse effects. One of the key events in the initial sensitization phase is the activation of dendritic cells. The GARD® assays use a prediction signature to analyze the immunological response of this key event that through a support vector machine give a positive decision value if a chemical is sensitizing. The first method of the GARD® assays, GARD®skin was developed for skin sensitization hazard assessment. Current study analyzed the dose-response relationship of GARD®skin for the potential to predict potency. A four-parametric (min, max, slope, ED50) log-logistic curve was used to form predicted dose-response curves to the experimental data points from seven chemicals of different CLP/GHS regulatory classifications. Comparison of the concentration at the inflection point to sensitizing values and the response variables to regulatory, human potency, and murine values suggest that GARD®skin through utilization of dose-response data has potential for skin sensitization potency classification.