How to assess respiratory sensitization of low molecular weight chemicals?

There are no validated and regulatory accepted (animal) models to test for respiratory sensitization of low molecular weight (LMW) chemicals. Since several decades such chemicals are classified as respiratory sensitizers almost exclusively based on observations in workers. However, both respiratory allergens (in which process the immune system is involved) as well as asthmagens (no involvement of the immune system) may induce the same type of respiratory symptoms. Correct classification is very important from a health's perspective point of view. On the other hand, over-classification is not preferable in view of high costs to overdue workplace engineering controls or the chemical ultimately being banned due to Authorities' decisions. It would therefore be very beneficial if respiratory sensitizers can be correctly identified and distinguished from skin sensitizers and non-sensitizers/respiratory irritants. The purpose of this paper is to consider whether LMW chemicals can be correctly identified based on the currently available screening methods in workers, and/or via in silico, in vitro and/or in vivo testing. Collectively, based on the available information further effort is still needed to be able to correctly identify respiratory sensitizers and to distinguish these from skin sensitizers and irritants, not at least because of the far-reaching consequences once a chemical is classified as a respiratory sensitizer.