This month, interdisciplinary scientific experts will meet in Lyon, France, to evaluate the potential of ethyl acrylate, methyl acrylate, and 2-ethylhexly acrylate, along with other substances, to increase the risk of cancer. The findings from this evaluation will be reported in Volume 122 of the International Agency for Research on Cancer (IARC) Monographs Program.
ToxStrategies recently published in the peer-reviewed literature a series of articles on these substances that are useful for integrating the relevant scientific data and assessing the high-dose cytotoxic mechanism-of-action information into assessments of human risk associated with exposure to these acrylates.
- Proctor et al., published in Regulatory Toxicology and Pharmacology, describes an adverse outcome pathway (AOP) for the cytotoxicity-driven forestomach tumors observed following ethyl acrylate gavage dosing. Incorporating data and results from multiple studies, a pre-molecular initiating event is postulated as sustained glutathione depletion, following epithelial cytotoxicity occurring at the site of contact. Data for butylated hydroxyanisole (BHA) provides support for this AOP.
- The journal Toxicology published a study by Suh et al., in which the authors reviewed 135 toxicology studies and high-throughput screening (HTS) data to assess acrylate carcinogenicity. In aggregate, the body of knowledge indicates that tumors observed from 2-ethylhexyl and ethyl acrylate occur by non-genotoxic key events at high doses and are secondary to site-of-contact irritation. Under realistic exposure conditions, however, the authors conclude that acrylates do not pose a human cancer hazard.
- A third article, by Thompson et al. in Regulatory Toxicology and Pharmacology, reviews the MOA by which tumors form in the forestomachs of rodents. Given that humans do not have a forestomach and the MOA is largely related to conditions that only occur at high doses and dose rates, the authors conclude that the tumor occurrence observed has little to no relevance to human exposures.
The three studies are as follows:
Proctor DM, Suh M, Chappell G, Borghoff SJ, Thompson CM, Wiench K, Finch L, Ellis-Hutchings R. 2018. An adverse outcome pathway (AOP) for forestomach tumors induced by non-genotoxic initiating events. Regul Toxicol Pharmacol 96:30–40, doi: 10.1016/j.yrtph.2018.04.016.
Suh M, Proctor DM, Chappell G, Rager JE, Thompson CM, Borghoff S, Finch L, Ellis-Hutchings R, Wiench K. 2018. A review of the genotoxic, mutagenic, and carcinogenic potentials of several lower acrylates. Toxicology 402–403:50–67, doi: 10.1016/j.tox.2018.04.006.
Thompson CT, Suh M, Chappell G, Borghoff S, Ellis-Hutchings R, Wiench K, Finch L, Proctor DM. 2018. Assessment of the mode of action underlying development of forestomach tumors in rodents following oral exposure to ethyl acrylate and relevance to humans. Regul Toxicol Pharmacol 96:178–189 doi: 10.1016/j.yrtph.2018.05.006.