Development of Mechanism-Based Structural Alerts for Respiratory Sensitization Hazard Identification

This study outlines how mechanistic organic chemistry
related to
covalent bond formation can be used to rationalize the ability of
low molecular weight chemicals to cause respiratory sensitization.
The results of an analysis of 104 chemicals which have been reported
to cause respiratory sensitization in humans showed that most of the
sensitizing chemicals could be distinguished from 82 control chemicals
for which no clinical reports of respiratory sensitization exist.
This study resulted in the development of a set of mechanism-based
structural alerts for chemicals with the potential to cause respiratory
sensitization. Their potential for use in a predictive algorithm for
this purpose alongside an externally validated quantitative structure–activity
relationship model is discussed.