The common indoor air pollutant α-pinene is metabolised to a genotoxic metabolite α-pinene oxide
Suramya Waidyanatha, Sherry R. Black, Kristine L. Witt, Timothy R. Fennell, Carol D. Swartz, Leslie Recio, Scott L. Watson, Purvi R. Patel, Reshan A. Fernando, Cynthia V. Rider
Abstract
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.