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Methacrylates and Respiratory Irritation

Methyl methacrylate (MMA) causes damage in the lining of the nose of rats in an area responsible for detection of smell.  Effects seen in animal studies typically are considered relevant to humans.  However, in contrast, MMA has been used by industry for over 60 years without apparently causing this lesion or having any detectable effect on workers ability to smell, despite workplace exposures in the past being many times higher than the levels that cause the effect in rodents.

In an attempt to understand this apparent difference, MPA commissioned a study to test the hypothesis that the observed difference in sensitivity between rats and humans may be the result of physiological and biochemical differences. Using a Weight-of-the Evidence (WoE) approach that analyses and integrates all the available evidence, the authors concluded that single and repeated exposure MMA inhalation studies in rat and mouse consistently indicate degenerative lesions of the main olfactory region as the most sensitive endpoint. They found numerous studies support a mode of action for MMA involving high concentrations of enzymes present in these tissues responsible for metabolizing MMA to methacrylic acid (MAA), an organic acid with irritating and corrosive proper­ties. Special studies and models examining the way MMA goes from inhaled air into these tissues in rats and humans point to differences in the structure and function that help explain these differences, and predict humans being between 3 to 8 times less sensitive than rats. This is consistent with the differences seen between the findings in studies in animals and the observations in workers, and suggests that an 8-hour time weighted average occupational exposure level (OEL) for worker exposure of 50 ppm MMA, the current regulatory limit in the U.S. and most countries, is justified.

These findings were presented in a Poster at the 2013 meeting of the Society of Toxicology in San Antonio, Texas.  Subsequently, the full scientific paper was published in the peer reviewed journal Regulatory Toxicology and Pharmacology (Hypothesis-based weight-of-evidence evaluation of methyl methacrylate olfactory effects in humans and derivation of an occupational exposure level).