Provocation of occupational asthma by non-specific irritation and its relevance for the classification of chemicals as respiratory allergens: a case study of methyl methacrylate
This paper by Pemberton, Hindle and Kimber revisits and updates the earlier comprehensive review that was undertaken in 2024 (https://pubmed.ncbi.nlm.nih.gov/35607993/). The authors focus on the 4 clinical case studies involving specific inhalation challenge (SIC) tests that are at the center of the classification and labelling activity in Europe, and that are claimed to demonstrate MMA causes occupational asthma. The review reveals that the available clinical data is unsuitable for accurate discrimination between allergic and non-specific irritant mechanisms, for which MMA is already classified (STOT SE 3 (Specific Target Organ Toxicity – Single Exposure, Category 3 - H335: May cause respiratory irritation). The review also taken into account experimental data derived from both animal studies and recently published in vitro assessments. Individually and collectively this data indicate that MMA lacks respiratory sensitising activity and that the bronchial responses observed in the SIC tests with MMA were the result of non-specific irritation and not sensitization. The authors generalize based on the limitations of the clinical evidence available on MMA and conclude that accurate regulatory classification of chemical respiratory allergens cannot rely solely on clinical studies. In this regard, the authors speculate that New Approach Methodologies (NAMs) being developed for the identification of respiratory sensitizers may be the way forward (More information). Link to paper https://doi.org/10.1016/j.yrtph.2026.106101