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Oral toxicokinetics of the indoor air pollutant, α-pinene, and its genotoxic metabolite, α-pinene oxide, in rodents and comparison to inhalation route of exposure

Suramya Waidyanatha1*, Timothy R. Fennell2, Sherry R. Black2, Melanie R. Silinski2, Gabriel A. Knudsen2, Reshan A. Fernando2, and Cynthia V. Rider1

Affiliations
1Division of Translational Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
2RTI International, Research Triangle Park, NC, USA

*Corresponding Author
Suramya Waidyanatha,PhD.
Division of Translational Toxicology
National Institute of Environmental Health Sciences
111 TW Alexander Dr.

Toxicology and Applied Pharmacology, (2026) Vol 513 https://doi.org/10.1016/j.taap.2026.117893 PMID: 42217586

DOI: https://doi.org/10.22427/NTP-DATA-500-103-003-000-2

Publication

Abstract

α-Pinene is a monoterpene with potential human exposure via oral and inhalation routes and has been associated with bladder hyperplasia and decrease in sperm counts in rodents following inhalation exposure. The toxicokinetics of α-pinene and α-pinene oxide was investigated following 7-day oral administration of α-pinene in rats (10, 50, and 150 mg/kg) and mice (50 mg/kg). α-Pinene was absorbed following oral administration. In rats, α-pinene systemic exposure (maximum concentration (Cmax) and area the under the concentration versus time curve (AUC)) increased less than dose-proportionally, except for Cmax in females, which increased proportionally with dose. While no sex difference was apparent at 10 mg/kg, female rats exhibited 2- to 3-fold higher exposure than males at 150 mg/kg. Oral bioavailability in rats was moderate at 10 mg/kg and higher in females (49%) than in males (32.7%)—bioavailability decreased at 150 mg/kg (females, 22.4%; males 4.89%). In mice, bioavailability was lower and similar between sexes (female, 18.5%; male, 19.8%). In both species, α-pinene was metabolized to α-pinene oxide. In rats, α-pinene oxide systemic exposure was similar to α-pinene, in contrast to inhalation exposure where α-pinene oxide concentration was lower than α-pinene. In mice, α-pinene oxide exposure was lower than that of α-pinene following oral administration. No apparent sex difference in α-pinene oxide systemic exposure were observed in either species. Both α-pinene and α-pinene oxide were distributed to mammary tissues. These findings will allow extrapolation of inhalation toxicology data to oral exposures and subsequent assessment of potential adverse human health impact to α-pinene exposure.

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