Skin sensitization structure-activity relationships for phenyl benzoates

The key to determining whether a chemical has the ability to behave as a contact allergen must reside ultimately in the structure and properties of that chemical rather than in the immune system. Quantitative structure-activity relationships (QSARs) have been demonstrated for a small number of series of chemicals in the past, using the relative alkylation index model based on this principle. In the present work, a carefully chosen range of phenyl benzoate esters has been synthesized such that they would have a single mechanism of action but otherwise would span important areas of parameter space—reactivity, skin penetration characteristics and biological response. Computer-based methods of analysis were used to generate a QSAR. The model showed that molecular volume and particularly the calculated logarithm of the partition coefficient (ClogP) were key parameters. Surprisingly, while chemical reactivity is a requirement for skin sensitization, it was not found to be an important variable in the QSAR. In conclusion, the study confirms that within a series of related chemicals it is possible to derive a useful QSAR.