Asthma
Technical Summary:
Asthma is typically divided into 2 sub-categories of the disease: extrinsic asthma — in which outbreaks are triggered by the presence of a specific allergen, such as pet dander, mold or dust and intrinsic asthma — for which no specific allergen can be identified. It is observed that intrinsic asthma is frequently, but not always, preceded by an infection of the patient's respiratory tract.
As it is usually extremely difficult to distinguish the mechanism(s) involved the term "asthmagen" has been developed to describe substances that are causally related to the development of asthma-like symptoms in individuals. Although clinical diagnosis of presence of asthma in a patient is well established the identification of the causative agent(s) is more difficult, and often not possible as this often involves the recognition of work industries associated with the development of asthma, or the identification of patterns in exposure to occupational or life-style substances that triggers asthma symptoms, followed by, in some cases by skin or blood testing to identify specific allergens.
This process of identifying causation by association is not precise as the clinical investigation is unavoidably retrospective and it is difficult to distinguish between agent(s)s that provoke asthma responses from the agent(s) that may have caused the onset of the asthma in the first place.
A recent and comprehensive review of the medical and other scientific literature linking MMA and methacrylates to asthma has been completed (Borak) This review concluded that MMA is not causally related to the development of asthma.
MMA is a high production volume chemical that has an extensive database of published and unpublished toxicological studies that have been the subject of three in depth, independent reviews by international governmental agencies. These reviews have also concluded that there is no convincing evidence that MMA causes asthma in humans.
Although some of these published studies appear to implicate MMA as a respiratory sensitizer/asthmagen, a thorough review of these publications does not support this conclusion.
In January 2001, the OECD (Organization for Economic Co-operation and Development) completed its Screening Inventory Dataset (SIDS) Initial Assessment Report (SIAR) for MMA concluding that "There is no convincing evidence that methyl methacrylate is a respiratory sensitizer in humans".
The review panel consisted of medical, toxicological and regulatory experts from the Governmental Agencies of the member OECD countries (Australia, Austria, Belgium, Canada, Czech republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Japan, Korea, Norway, Poland, Portugal, Slovak Republic, Spain, Sweden, Switzerland, The Netherlands, UK, USA) as well as from the European Commission, UNEP, and WHO.
Soon thereafter, in April 2001, the European Union finalized its Risk Assessment for MMA. This six-year risk assessment reviewed published and unpublished (company confidential) studies/reports on MMA, concluding that "no convincing evidence was found that MMA acts as a respiratory sensitiser in humans" in Chapter (section) 4.1.2.5.
The review panel consisted of the leading medical and toxicological experts of the Competent Authorities in the European Union as well as the World Health Organisation. The report was also reviewed and approved by an independent panel of International Peer Scientists/Professors/clinicians comprising the Scientific Committee for Toxicity, Ecotoxicity and the Environment (CSTEE). The review specifically addressed asthma and concludes: "The literature reports isolated cases of asthma in the context of MMA exposure. Substance-specific bronchoconstriction or delayed asthmatic responses respectively were confirmed only in very few cases. Asthmatic reactions seem to be restricted to exposure levels which primarily result in respiratory tract irritation".
More recently, in 2002, Health Canada (HC) actually reversed an earlier decision (1996) to classify MMA as a respiratory sensitizer (which required all products containing MMA, or MMA residues (polymers etc.); to be labelled "Contains a respiratory sensitizer"). This decision was based upon the conclusion that, "on balance, there is insufficient evidence at this time to regard MMA as a respiratory sensitizer". Accordingly HC has removed MMA from their list of known respiratory sensitizers. The ruling for MMA can be seen on the Health Canada (WHIMIS) website.
In summary, these three international agencies, after thorough scientific reviews concluded that MMA should not be regarded as an asthma causing chemical or "asthmagen" was based upon the fact that:
- Despite MMA's widespread use it had been implicated in only a small number of clinical case histories reported in the literature and,
- that there was (1) inadequate evidence of an allergic mechanism, and (2) the case reports in the literature were more consistent with individuals that had developed asthma for some other reason and this condition had been aggravated by their occupation exposure to an irritant vapour (MMA).
The lack of a clear causal relationship between MMA exposure and development of the asthmatic condition meant that MMA should not be regarded as an "asthmagen."
References:
Borak J., Fields C., Andrews L. and Pemberton M. Methyl Methacrylate and Respiratory Sensitization: A Critical Review. Critical Reviews in Toxicology. 2011; 41(3): 230-268. Click here for publication.
