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The common indoor air pollutant α-pinene is metabolized to a genotoxic metabolite α-pinene oxide

Suramya Waidyanatha, Sherry R. Black, Kristine L. Witt, Timothy R. Fennell, Carol Swartz, Leslie Recio, Scott L. Watson, Purvi R. Patel, Reshan A. Fernando, and Cynthia V. Rider

Taylor & Francis Online (2022) DOI: https://doi.org/10.1080/00498254.2022.2070047 PMID: 35473450
DOI: https://doi.org/10.22427/NTP-DATA-002-03031-0019-0000-9

In Vitro Metabolism of α-pinene To α-pinene oxide



1.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.
2.To provide human relevant context for data generated in animal models and explore mechanism, we undertook in vitro studies to investigate the metabolism of a-pinene to a-pinene oxide and mutagenicity of α-pinene and a-pinene oxide.
3.a-Pinene oxide was formed in rat and human microsomes and hepatocytes with some species difference. Based on area under the concentration versus time curves, the formation of a-pinene oxide was approximately 2- to 4-fold higher in rats than in humans.
4.While rat microsomes cleared a-pinene oxide faster than human microsomes, the clearance of a-pinene oxide in hepatocytes was similar between species.
5.α-Pinene was not mutagenic with or without induced rat liver S9 in Salmonella typhimurium or Escherichia coli when tested up to 10,000 mg/plate while α-pinene oxide was mutagenic at ≥25 µg/plate.
6.a-Pinene was metabolized to a-pinene oxide under the conditions of the bacterial mutation assay although the concentration was approximately 3-fold lower than the lowest a-pinene oxide concentration that was positive in the assay, potentially explaining the lack of mutagenicity observed with a-pinene.