Blog Index
The journal that this archive was targeting has been deleted. Please update your configuration.
Navigation

MPA Other Developments

Epidemiologist Concludes that MMA is Not Associated with Cancer Risk

Methyl methacrylate (MMA) is a “monomer” used as a raw material to make various “polymers”, which are plastics and resins used in many important applications. Persons who work in facilities that manufacture MMA or that manufacture polymers with MMA can be exposed to MMA.

Epidemiology studies are used to investigate the relationship between, for example, exposure to a chemical in the workplace and the occurrence of diseases, such as a specific type of cancer. A cancer mortality study compares the observed rate of cancer mortality in the group of individuals being studied with the rate of cancer mortality in the general population with the same age, sex distribution and, if possible, life-style habits, etc. Since there are many risk factors for developing cancer, including, age, genes, immunity, viruses and life styles (smoking, drinking, sunbathing and diet), the design, conduct and interpretation of epidemiology studies is complex.

To date six epidemiology studies have been conducted on occupational (worker) populations with exposure to MMA and reported in the open, scientific literature. Four studies were commissioned by industry on workers in the MMA-monomer production and/or PMMA sheet production industry (polymerized MMA). Two studies were made on orthopedic surgeons, some of which implant medical devices based upon MMA and PMMA (i.e., bone cements).

Collectively, no consistent elevations of specific cancer types were reported across the available studies. The production industry investigations found an increase in colorectal cancer in early studies, but this was not confirmed in follow-up or more extensive studies. In the studies on orthopedic surgeons, an increased cancer rate for esophagus and myeloproliferative cancers was reported in one study and increased breast cancer in another. Overall the epidemiology studies do not support a causal link between these cancers and MMA exposure. First, these cancer types were not elevated in the larger studies conducted by industry as would be expected if there was a causal relationship between MMA and cancer in humans. Second, independent review of these studies by a recognized epidemiologist, Dr. G. Swaen, identified limitations in the methodology used in the orthopedic surgeon studies that make a conclusion of a causal relationship between MMA exposure and cancer unreliable (Swaen, 2019).

With this recent opinion, Dr. Swaen confirmed the conclusion of Dr. J. Tomenson and coworkers in 2005. They concluded that the available human data are not in support of an increased cancer risk from occupational exposure to MMA, based on an exhaustive review of the then available epidemiologic literature. Dr. Swaen goes on to highlight that in his opinion the industry studies conducted in the United States and Great Britain were of sufficient size, statistical power and design, that they still represent the most comprehensive information available on the occurrence of cancer in humans exposed to high concentrations of MMA, and that they demonstrate that exposure to MMA, even at relatively high concentrations, is not associated with cancer risk.

Canadian Government Finds Methacrylic Acid and n-butyl methacrylate Pose Low Risks to Human Health and the Environment

In October 2018, Health Canada (HC) and Environmental and Climate Change Canada (ECCC) released the results of their screening assessment of “the acrylates and methacrylates group.”[1] That group comprised six substances, including methacrylic acid (MAA) and n-butyl methacrylate (n-BMA). HC and ECCC concluded that the six substances, including MAA and n-BMA, “are not entering the environment in a quantity or concentration or under conditions that have or may have an immediate or long-term harmful effect on the environment or its biological diversity or that constitute or may constitute a danger to the environment on which life depends.”[2] They also concluded these substances “are not entering the environment in a quantity or concentration or under conditions that constitute or may constitute a danger in Canada to human life or health.” [3]

The Methacrylate Producers Association (MPA) concurs with these conclusions. MAA and n-BMA are used as building blocks for polymers and are used up in the production of the polymers. The general public would have exposure to very few, if any, products containing MAA or n-BMA themselves, except for very low residual levels in polymers. Thus, a statement that a given final product (e.g., a plastic, coating or lubricant) contains MAA or n-BMA may mean that these monomers are used to produce polymers that in turn are used to make the final product. Readers are urged to evaluate statements about MAA and n-BMA use accordingly.

Regarding the use of liquid, unreacted methacrylate monomers in cosmetics, see MPA’s statement.


[1] Environmental and Climate Change Canada and Health Canada. Screening assessment acrylates and methacrylates group (October 2018), https://www.canada.ca/en/environment-climate-change/services/evaluating-existing-substances/screening-assessment-acrylates-methacrylates-group.html.

[2] Id., synopsis.

[3] Id.

Toxicological Assessment of Lower Alkyl Methacrylate Esters by a Category Approach

The health effects of lower alkyl methacrylate esters (methyl, ethyl, n-butyl, iso-butyl and 2-ethylhexyl) are well understood. MMA has the most comprehensive data set and although the data on the other esters is more limited their close structural similarity to MMA enables prediction of their hazard properties without the need to conduct unnecessary testing in animals. This is commonly referred to as the “reading across” of data between a group of structurally related chemicals or “category”. In an attempt to promote the use and consistency of Read Across within the EU REACH[1] process the EU Regulatory Agency has issued an Assessment Framework, referred to as the RAAF (ECHA, 2017[2]). In response MPA sponsored a study of the health effects data on lower alkyl methacrylate esters (C1-C8) and an assessment of how well the RAAF criteria could be satisfied. This study was published in a peer reviewed journal and is available under open access for download at https://doi.org/10.1016/j.yrtph.2017.11.013.

The study confirmed that these chemicals have similar structures, chemical reactivity and fate within the body and consequently Read Across could be used to fill in data gaps for health effects with high confidence. By developing Read Across for these chemicals MPA member companies have gained a far deeper insight into the health effects of lower alkyl methacrylate esters that can be used to better promote their safe handling and use.

[1] https://echa.europa.eu/regulations/reach/legislation

[2] European Chemicals Agency, 2017. Read-Across Assessment Framework (RAAF). https://echa.europa.eu/documents/10162/13628/raaf_en.pdf

Lower alkyl methacrylate esters are shown not to be of concern for cancer

Lower alkyl methacrylate esters1 are chemically-reactive molecules that are used to produce methacrylate-based plastics and resins. Their chemical reactivity (Michael reactivity) results in them combining with proteins such that they can be skin sensitizers in humans. This chemical reactivity also means that they can potentially react with other macromolecules such as DNA; raising the question of whether they might cause genetic damage; and therefore, be of concern for cancer. 

To investigate this question, MPA sponsored Dr. Richard Albertini, an independent and eminent genotoxicity expert at the University of Vermont, to review the extensive studies on the lower alkyl methacrylates and publish his findings in a peer-reviewed journal. Dr. Albertini found that in studies in bacteria, which are often used to identify chemicals that might cause cancer in humans, the lower alkyl methacrylates did not cause permanent alterations in DNA. In tests using animal cells in glassware (in vitro) with very high concentrations of the methacrylates, there was disruption or breakages of chromosomes, but Dr. Albertini concluded there was no convincing evidence that the lower alkyl methacrylates cause this type of damage in live animals. This is consistent with the lack of carcinogenicity of methyl methacrylate observed in studies of both animals and humans. Dr. Albertini explained the observation in glassware as likely being due to the high concentrations and to generation of metabolites under these artificial conditions – metabolites that do not occur in animals and humans when exposed to these chemicals. Overall, Dr. Albertini concluded that lower alkyl methacrylate esters are not of concern for cancer.

1The lower alkyl methacrylates are methyl methacrylate (MMA), the largest volume monomer, as well as ethyl methacrylate (EMA), hydroxyethyl methacrylate (HEMA), n-, i- and t-butyl methacrylate (BMA) and 2 ethyl hexyl methacrylate (2-EHMA), as well as methacrylic acid (MAA).

Statement Regarding AOEC Classification of Methyl Methacrylate

In its online Exposure Code database, the Association of Occupational and Environmental Clinics (AOEC) codes methyl methacrylate (MMA) as an asthmagen and respiratory sensitizer.  A number of thorough and careful evaluations of MMA have concluded it cannot be classified as an asthmagen or respiratory sensitizer.

The AOEC exposure codes, which were assigned by a single reviewer, do not comport with the findings of other scientific bodies. The Methacrylate Producers Association believes that the science does not support a finding that MMA is an asthmagen or a respiratory sensitizer.  For more information, see MPA's position paper.

Department of Transportation and Congress Set New Rail Transportation Rules Applicable to Methyl Methacrylate

With a final rulemaking by the Department of Transportation (DOT) in May 2015, which was modified by a subsequent Act of Congress in December 2015, the Department and Congress set new safety rules for rail transportation of flammable liquids. Although primarily targeting crude oil and ethanol shipments, the rule applies to shipment of all Class 3 flammable liquids and thus to methyl methacrylate (MMA). MPA had commented on the Department’s proposed rules, expressing concern about the need for such rules given the methacrylate industry’s voluntary adoption of higher-safety tank cars, as well as the foreshortened and likely unrealistic timeline proposed for implementing required retrofits (or obtaining new tank cars built to the new DOT-117 specifications). DOT’s final rule was not adequately responsive to such concerns. Congress stepped in with provisions in the” Fixing America’s Surface Transportation Act” (FAST Act) which modified the DOT rule. For Packing Group II substances such as MMA, improved tank cars must be used for transport after May 1, 2029, consistent with MPA’s comments requesting an extended period for implementation of the new rules. DOT can extend this deadline by two years if it determines there is insufficient shop capacity to meet the 2029 deadline. Further, in lieu of meeting the full DOT-117 standards, retrofitted tanks cars may comply with DOT-117R standards, which many tanks cars in MMA service already meet. The voluntary adoption of tank car enhancements by MMA members has contributed to an outstanding safety record for rail transportation of MMA.

ACGIH® Recommended TLVs for Methyl Methacrylate

In response to recent announcements by American Conference of Governmental Industrial Hygienists (ACGIH), MPA comments to ACGIH supporting the recommended Threshold Limit Values (TLVs) for Methyl Methacrylate (MMA).  These limits are consistent with occupational exposure limits set by the European Union SCOEL (Scientific Committee on Occupational Exposure Limits).  However, two statements concerning potential respiratory and skin sensitization have been included that are not supported by a wider evaluation of the literature, and could lead to misunderstanding by ACGIH’s intended audiences.

Health Review on Asthma

The health effects of MMA are well understood. MMA liquid is recognized as being irritating to the eyes and is a weak skin-sensitizer that may cause skin allergy (allergic contact dermatitis) following skin contact. High concentrations of the vapor are also irritating to the respiratory system. As irritant vapors (cold air, smoke etc.) may worsen the symptoms in individuals that have sensitive airways, such as asthmatics it is not surprising that there has been much debate and confusion about whether or not MMA exposure can also cause respiratory sensitization (occupational asthma).  Dr. Jonathan Borak, MD, DABT (Departments of Epidemiology and Public Health and Medicine, Yale University) conducted a critical review all the available information and the results are included in a publication in Critical Reviews in Toxicology in which he concludes that the "weight of evidence" supports the conclusion that "MMA is not a respiratory sensitizer". For for information, see Methacrylates and Asthma.

REACH

REACH is the European Union (EU) regulation for Registration, Evaluation, Authorisation and Restriction of Chemicals. It entered into force on 1st June 2007 with the objective to protect human health and the environment from the risks that can be posed by chemicals.

The Methacrylates REACH Task Force, comprised of MPA’s member companies along with other manufacturers in the EU and Japan, successfully completed the registration of the lower methacrylates (MAA, MMA, EMA, nBMA, iBMA and 2-EHMA) as a group of related esters (or category) in October 2010, before the December 1st deadline for high production volume chemicals (>1000 tpa). The registrations included the conduct of several studies to meet data requirements for compounds in the highest tonnage band, a comprehensive hazard assessment for each compound, as well as an assessment of safe handling conditions for identified uses of each compound.

Assessment of the Skin Sensitizing Potency of the Lower Alkyl Methacrylate Esters

A 2014 publication in Regulatory Toxicology and Pharmacology, "Assessment of the skin sensitising potency of the lower alkyl methacrylate esters" reports that Methyl Methacrylate and other lower alkyl methacrylates had weak skin sensitizing potency.

Methacrylate Polymers Do Not Cause Skin Sensitization When Handled

A 2014 publication in Regulatory Toxicology and Pharmacology, "Risk Assessment of residual monomer migrating from acrylic polymers and causing allergic contact dermatitis during normal handling and use" reports that methacrylate polymers do not cause skin sensitization when handled.

For more information, see MPA Archived Developments.