Behavior of Chemical Respiratory Sensitizers in in Vitro Methods for Skin Sensitization

Respiratory sensitization induced by chemicals is a critical occupational and public health issue because it is associated with allergic asthma or other pulmonary symptoms. However, there are no validated test methods to identify the potential to cause respiratory sensitization. In this study, to investigate the behavior of respiratory sensitizers in a skin sensitization test method, 14 respiratory sensitizers were tested with the human cell line activation test (h-CLAT). h-CLAT was positive for seven of the 14 respiratory sensitizers, including all four diisocyanate used industrially as polyurethane materials. Furthermore, for three acid anhydrides negative in h-CLAT, we conducted a modified h-CLAT (a short-time exposure method using liquid paraffin), and phthalic anhydride proved positive. Among the seven h-CLAT negatives, at least four chemicals were positive in the direct peptide reactivity assay (DPRA - in chemico skin sensitization test method listed in OECD TG 442C). Therefore, to identify the potential to cause respiratory sensitization, it is necessary to not only the application to in vitro skin sensitization test based on the common key events but also the combination of these existing skin sensitization tests with the new approach methods, which is developed based on the specific mechanism of chemical respiratory allergy.