QSAR Study of Skin Sensitization Using Local Lymph Node Assay Data

Abstract: Allergic Contact Dermatitis (ACD) is a common work-related skin disease that often develops as a result of repetitive skin exposures to a sensitizing chemical agent. A variety of experimental tests have been suggested to assess the skin sensitization potential. We applied a method of Quantitative Structure-Activity Relationship (QSAR) to relate measured and calculated physical-chemical properties of chemical compounds to their sensitization potential. Using statistical methods, each of these properties, called molecular descriptors, was tested for its propensity to predict the sensitization potential. A few of the most informative descriptors were subsequently selected to build a model of skin sensitization. In this work sensitization data for the murine Local Lymph Node Assay (LLNA) were used. In principle, LLNA provides a standardized continuous scale suitable for quantitative assessment of skin sensitization. However, at present many LLNA results are still reported on a dichotomous scale, which is consistent with the scale of guinea pig tests, which were widely used in past years. Therefore, in this study only a dichotomous version of the LLNA data was used. To the statistical end, we relied on the logistic regression approach. This approach provides a statistical tool for investigating and predicting skin sensitization that is expressed only in categorical terms of activity and non-activity. Based on the data of compounds used in this study, our results suggest a QSAR model of ACD that is based on the following descriptors: nDB (number of double bonds), C-003 (number of

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