Methyl methacrylate and respiratory sensitization: A Critical review

Abstract

Methyl methacrylate (MMA) is a respiratory irritant and dermal sensitizer that has been associated with occupational asthma in a small number of case reports. Those reports have raised concern that it might be a respiratory sensitizer. To better understand that possibility, we reviewed the in silico, in chemico, in vitro, and in vivo toxicology literature, and also epidemiologic and occupational medicine reports related to the respiratory effects of MMA. Numerous in silico and in chemico studies indicate that MMA is unlikely to be a respiratory sensitizer. The few in vitro studies suggest that MMA has generally weak effects. In vivo studies have documented contact skin sensitization, nonspecific cytotoxicity, and weakly positive responses on local lymph node assay; guinea pig and mouse inhalation sensitization tests have not been performed. Cohort and cross-sectional worker studies reported irritation of eyes, nose, and upper respiratory tract associated with short-term peaks exposures, but little evidence for respiratory sensitization or asthma. Nineteen case reports described asthma, laryngitis, or hypersensitivity pneumonitis in MMA-exposed workers; however, exposures were either not well described or involved mixtures containing more reactive respiratory sensitizers and irritants. The weight of evidence, both experimental and observational, argues that MMA is not a respiratory sensitizer.

Keywords::

• Acrylates
• asthma
• cross-reactivity
• epidemiology
• exposure assessment
• in chemico
• in silico
• LLNA
• mechanisms
• metabolism
• mixtures
• occupational respiratory irritation
• toxicology

Acknowledgements

We express our gratitude to Leslie J. Ungers, MS, CIH, and DePuy Orthopedics for providing us access to and permission to cite their previously unpublished MMA exposure data. We are also grateful for the excellent technical assistance of Greg Sirianni, MS, CIH, and Catherine Salipante-Zaidel, MEM, and the bibliographic support of Jannette Rivera.

Declaration of interests

This manuscript was supported by a contract between the Methacrylate Producers Association and Jonathan Borak & Company. Jonathan Borak and Cheryl Fields are employees of Jonathan Borak & Company, which provides consulting services on environmental and occupational health issues to government and private clients. Dr. Andrews is Senior Toxicologist at The Dow Chemical Company and Dr. Pemberton is Director of Product Integrity at Lucite International; both companies are members of the Methacrylate Producers Association. The authors have sole responsibility for the writing and content of the paper.

Notes

¹The current American Conference of Industrial Hygienists (ACGIH) Biological Exposure Indice (BEI) for methanol is 15 mg/L in end-of-shift urine (ACGIH, 2010).