Substance-Specific Issues

Methyl methacrylate; classification with respect to respiratory tract sensitization

Substance:

Methyl methacrylate; CAS No. 80-62-6

Issue:

Does methyl methacrylate fall within the Controlled Products Regulations (CPR) criteria for respiratory tract sensitization?

Background:

Acrylates such as methyl methacrylate (MMA) are widely used in the production of polymers like surface coated resins, plastics and in medicine for dental implants and as bone cement. MMA is a well known contact sensitizer but only a few cases of respiratory sensitization have been reported in the literature.

After several years of exposure, a dental assistant exposed to MMA at work began to experience chest tightness, dyspnea, and cough, which persisted for several hours after exposure to small amounts of MMA. In tests designed to mimic his work situation, asthmatic symptoms (a fall in peak expiratory flow or PEF of 24%) developed immediately after a 20 minutes exposure to MMA and resolved over two hours. The test was repeated one week later and provoked a similar immediate asthmatic reaction [1].

After 11 years working in an operating room handling bone cement, a nurse developed respiratory symptoms characterised by a persistent cough with wheezing and breathlessness. Bronchial provocation were carried and a late asthmatic reaction - a fall in forces expiratory volume (FEV) of 25% - occurred after challenge with MMA [2].

A dental nurse who had been exposed to various acrylates for about 27 years started to experience hoarseness and soreness of the throat, nasal stuffiness and dyspnea when preparing orthodontal fixatives. Inhalation challenge test with Paladur^R (resin containing a number of chemicals including methyl methacrylate) liquid and powder (polymethyl methacrylate) induced mucosal changes and symptoms of the upper respiratory tract, diagnosed as immediate hypersensitivity rhinitis and pharyngitis. The challenge test did not induce significant reactions in FEV, but 16 h after the challenge test the PEF was reduced by 20% [3]. The authors report that the challenge test was done with the dental acrylate resin product which contain other components as well as impurities. To ascertain what component is causing the asthmatic reactions, provocations with all compounds should have been undertaken which was, in this study, not practicable.

Savonius et al. reported three cases of respiratory sensitization that they linked with exposure to MMA [4]. However, the information used in relation to chemical nomenclature was confusing and an erratum was published to specify the chemical identity of the substances [5]. The first patient (M-1) is described as atopic and therefore, according to the CPR criteria, cannot be used for classification. The second patient, M-2, was exposed to the polymer rather than the monomer. The third patient, M-3, was a woman who had worked as a dental technician for 20 years. She experienced a feeling of tickling in her throat, yawning, cough, tiredness and chest tightness. Prick tests with methacrylate and polyethyleneglycoldimethacrylate were negative. A fall in peak expiratory flow of 26% was observed when challenged with the product she was using.

Considerations:

As stated in the Health Canada Reference Manual interpretation / discussion of section 56 of the CPR, when determining whether or not a chemical falls within the CPR criteria for sensitization, the number of cases reported in relation to the size of the population that has been exposed and the extent of the exposure should be taken into consideration [6]. For example, a high-production-volume chemical, used in large quantities in many workplaces would not warrant classification if only a few cases of sensitization had been reported over a period of several years.

Conclusion:

As only very few cases have been reported in the literature with this widely used chemical, MMA would not fall within the CPR criteria for respiratory tract sensitization.

Note: should the number of cases increase or should new cases be reported in the literature, the potential of MMA to induce respiratory sensitization may be reevaluated.

References:

1. Losewicz S. et al (1985), Thorax, Vol 40, Number 11, pages 836-839.
   
   
2. Pickering C.A. et al. (1986), British Medical Journal, Vol 292, Number 6532, pages 1362-1363.
   
   
3. Piirilä P. et al, (1998), Clinical and Experimental Allergy, Volume 28, pages 1404-1411.
   
   
4. Savonius B. et al (1993), Clinical and Experimental Allergy, Volume 23, pages 416-424.
   
   
5. Savonius B. et al (1993), Clinical and Experimental Allergy, Volume 23, page 712.
   
   
6. Health Canada; "Reference Manual for the WHMIS Requirements of the Hazardous Product Act and Controlled Products Regulations".