A quantitative structure–Activity relationship study of the skin irritation potential of phenols

• Published in: Toxicology in vitro 1999-12, Vol.13 (6), p.915-922
• Main Authors: Hayashi, M., Nakamura, Y., Higashi, K., Kato, H., Kishida, F., Kaneko, H.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Chemical and industrial products toxicology. Toxic occupational diseases; logP; Medical sciences; molecular orbital methods; phenols; quantitative structure-activity relationships; quantitative structure–activity relationships (QSARs); skin irritation; Toxicology; Various organic compounds
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/S0887-2333(99)00077-6

Quantitative structure–activity relationships (QSARs) for skin irritation potential were studied using twenty-four phenols. Based on the hypothesis that skin irritation is induced by reaction of phenols with macromolecules present in epidermal and dermal levels of the skin, the following descriptors for QSAR were selected, the absolute hardness (N) calculated from HOMO (the highest occupied molecular orbital) and LUMO (the lowest unoccupied molecular orbital) energy levels for reactivity, and logP (octanol–water partition coefficient) for permeability. Using these descriptors, we fitted a regression function to the set of skin irritation scores obtained from an in vivo study, which allowed derivation of equations (r=0.85). The equations were verified with six additional phenols, showing good correlations with the expected skin irritation scores. From the above findings, the equations can be considered useful for predicting the skin irritation potential of phenol compounds.