Abstract: The Ferguson principle has been widely used in toxicology to separate or indicate possible mechanisms for acute toxic effects of chemicals. However, this principle has never been adequately tested because of the lack of a database containing a sufficient number of both types of chemicals, non-reactive and reactive, that the Ferguson principle purports to separate. Such a database is now available. In this report a theoretical framework for the Ferguson principle is presented, regarding one of the acute toxicological effects of volatile airborne chemicals: sensory irritation. Previously obtained results on series of non-reactive and reactive chemicals are then used to demonstrate that the Ferguson principle can be extended to reactive chemicals by adding chemical reactivity descriptors to the physicochemical descriptors required by the Ferguson principle. This approach can be successful, provided that specific chemical reactivity mechanisms can be identified for the reactive chemicals of concern. The findings suggest that it is possible to replace the empirical Ferguson principle by formal mechanistic equations which will provide a better foundation for the understanding of the mechanisms by which airborne sensory irritants exert their action.