The common indoor air pollutant α-pinene is metabolised to a genotoxic metabolite α-pinene oxide
Waidyanatha, S., Black, S. R., Witt, K. L., Fennell, T. R., Swartz, C., Recio, L., Watson, S. L., Patel, P., Fernando, R., & Rider, C. V. (2022). The common indoor air pollutant α-pinene is metabolised to a genotoxic metabolite α-pinene oxide. Xenobiotica, 52(3), 301-311. Advance online publication. https://doi.org/10.1080/00498254.2022.2070047
α-Pinene caused a concentration-responsive increase in bladder hyperplasia and decrease in sperm counts in rodents following inhalation exposure. Additionally, it formed a prospective reactive metabolite, α-pinene oxide. To provide human relevant context for data generated in animal models and explore potential mechanism, we undertook studies to investigate the metabolism of α-pinene to α-pinene oxide and mutagenicity of α-pinene and α-pinene oxide.α-Pinene oxide was formed in rat and human microsomes and hepatocytes with some species differences. Based on area under the concentration versus time curves, the formation of α-pinene oxide was up to 4-fold higher in rats than in humans. While rat microsomes cleared α-pinene oxide faster than human microsomes, the clearance of α-pinene oxide in hepatocytes was similar between species.α-Pinene was not mutagenic with or without induced rat liver S9 in Salmonella typhimurium or Escherichia coli when tested up to 10 000 µg/plate while α-pinene oxide was mutagenic at ≥25 µg/plate.α-Pinene was metabolised to α-pinene oxide under the conditions of the bacterial mutation assay although the concentration was approximately 3-fold lower than the lowest α-pinene oxide concentration that was positive in the assay, potentially explaining the lack of mutagenicity observed with α-pinene.