The importance of exposure determination during Specific Inhalation Challenge (SIC) tests for the exclusion of nonspecific irritation.

Work-related asthma (WRA) comprises asthma caused by chemicals in the workplace (occupational asthma, or OA) and preexisting asthma made worse by chemicals and conditions (work-exacerbated asthma, or WEA). Distinguishing these two mechanisms is extremely challenging but imperative for effective health management and regulation under global chemical regulations. The Specific Inhalation Challenge (SIC) test is considered by clinicians as the gold standard for identifying OA. However, an exposure reconstruction exercise based on the case study of methyl methacrylate, currently undergoing harmonized classification and labeling within Europe suggests that greater rigor may be needed when conducting these tests if false positive results, i.e., from nonspecific irritation are to be avoided. Accurate simulation of actual workplace conditions combined with direct measurement of peak exposure levels will likely improve test specificity.