Comprehensive analysis of chronic rodent inhalation toxicity studies for methyl acrylate with attention to test conditions exceeding a maximum tolerated concentration.

Abstract MA is a chemical intermediate, manufactured and processed within closed systems. While so far available subacute to chronic inhalation toxicity studies performed in compliance with OECD TG principles gave no indication of any carcinogenic potential for MA, a recent 2-year inhalation study with F344/DuCrlCrlj rats published in 2017 by the JBRC showed a statistically significant increase of squamous cell carcinoma in the nasal cavity of male rats at the highest tested concentration of 160 ppm. However, the results of the different studies in total indicate that this high concentration exceeded the MTC. As MA has a low potential for genotoxic and mutagenic activity, the increased tumour incidence can be attributed to a non-genotoxic mechanism, namely to a strong inflammatory response observed in this study. Together with mechanistic and epidemiologic data for other compounds related to nasal carcinogenesis via this mode of action, it can be concluded that the relevance of this increased tumour incidence in male rats for humans is questionable. Also, a long-term exposure to higher concentrations of MA is highly unlikely to be reached in the environment or at workplaces. Therefore, a risk for humans including cancer hazard is considered implausible.