LP-61 Methyl methacrylate (MMA) is respiratory irritant, but not a respiratory sensitiser

Methyl methacrylate (MMA) is classified under the Globally Harmonized System (GHS) as a weak skin sensitizer and a skin and respiratory irritant. Recently, it has been proposed that MMA be classified as a respiratory sensitizer. This proposal was primarily based on the interpretation of a very limited number of case reports, which lacked sufficient background information and documentation for a thorough assessment. The aim of our new study was to assess the potential of MMA to induce respiratory sensitization using an in vitro test system, ALIsens®, which is currently under review by the OECD for predicting the respiratory sensitization potential of chemicals in regulatory assessments. In previous examinations, the ALIsens® model gave promising results, successfully discriminating respiratory sensitizers from skin sensitizers and non-sensitizers (Burla S et al. 2025) . The test system utilizes a three-dimensional (3D) configuration incorporating three human cell lines: alveolar type II epithelial (A549), endothelial (EA.hy926), and monocytes (THP-1). ALIsens® was exposed to MMA, resulting in final exposure dose of 250 µg/cm 2 and 500 µg/cm 2 , respectively. The model was concurrently exposed to a respiratory sensitizer, a skin-sensitizer and a non-sensitizer. The expression of CD54, CD86, and TSLPr markers was measured on the surface of dendritic-like THP-1 cells by flow cytometry. Flow cytometry analysis demonstrated consistent responsiveness of the test system upon exposure to the known respiratory sensitizer, as shown by the increased relative mean fluorescence intensity (rMFI) value of the TSLPr cell surface marker. Upon exposure to MMA, the results for the TSLPr marker clearly show that the expression is well below the threshold of 150%. These results indicate that MMA is identified as non-respiratory sensitizer and that the proposed classification and labeling as a respiratory sensitizer are not justified.

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Publication Details

Journal
Toxicology Letters
Published
2025-09-01
DOI
https://doi.org/10.1016/j.toxlet.2025.07.1072
Primary Topic
Inhalation and Respiratory Drug Delivery
Type
article
Field-Weighted Citation Impact
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article

LP-61 Methyl methacrylate (MMA) is respiratory irritant, but not a respiratory sensitiser

Arno C. Gutleb, Sabina Burla, Karin Wiench, Tobias Sommer et al.
Toxicology Letters
Inhalation and Respiratory Drug Delivery
article

LP-61 Methyl methacrylate (MMA) is respiratory irritant, but not a respiratory sensitiser

Arno C. Gutleb, Sabina Burla, Karin Wiench, Tobias Sommer, G. Radicchio
article en

Abstract

Methyl methacrylate (MMA) is classified under the Globally Harmonized System (GHS) as a weak skin sensitizer and a skin and respiratory irritant. Recently, it has been proposed that MMA be classified as a respiratory sensitizer. This proposal was primarily based on the interpretation of a very limited number of case reports, which lacked sufficient background information and documentation for a thorough assessment. The aim of our new study was to assess the potential of MMA to induce respiratory sensitization using an in vitro test system, ALIsens®, which is currently under review by the OECD for predicting the respiratory sensitization potential of chemicals in regulatory assessments. In previous examinations, the ALIsens® model gave promising results, successfully discriminating respiratory sensitizers from skin sensitizers and non-sensitizers (Burla S et al. 2025) . The test system utilizes a three-dimensional (3D) configuration incorporating three human cell lines: alveolar type II epithelial (A549), endothelial (EA.hy926), and monocytes (THP-1). ALIsens® was exposed to MMA, resulting in final exposure dose of 250 µg/cm 2 and 500 µg/cm 2 , respectively. The model was concurrently exposed to a respiratory sensitizer, a skin-sensitizer and a non-sensitizer. The expression of CD54, CD86, and TSLPr markers was measured on the surface of dendritic-like THP-1 cells by flow cytometry. Flow cytometry analysis demonstrated consistent responsiveness of the test system upon exposure to the known respiratory sensitizer, as shown by the increased relative mean fluorescence intensity (rMFI) value of the TSLPr cell surface marker. Upon exposure to MMA, the results for the TSLPr marker clearly show that the expression is well below the threshold of 150%. These results indicate that MMA is identified as non-respiratory sensitizer and that the proposed classification and labeling as a respiratory sensitizer are not justified.

Toxicology LettersVol. 411
Evonik (Germany) (DE), BASF (Germany) (DE)
Openalex Percentile: Top 65%
Inhalation and Respiratory Drug Delivery
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