Evaluation of urinary limonene metabolites as biomarkers of exposure to greenness

• Published in: Environmental research 2024-03, Vol.245, p.117991-117991, Article 117991
• Main Authors: Xie, Zhengzhi, Sutaria, Saurin R., Chen, Jin Y., Gao, Hong, Conklin, Daniel J., Keith, Rachel J., Srivastava, Sanjay, Lorkiewicz, Pawel, Bhatnagar, Aruni
• Format: Article
• Language: English
• Subjects: Biogenic volatile organic compounds (BVOC); Biomarker; Data-independent acquisition (DIA); Greenness exposure; LC-MS; Limonene
• ISSN: 0013-9351; 1096-0953
• DOI: 10.1016/j.envres.2023.117991

Exposure to plants is known to improve physical and mental health and living in areas of high vegetation is associated with better health. The addition of quantitative measures of greenness exposure at individual-level to other objective and subjective study measures will help establish cause-and-effect relationships between greenspaces and human health. Because limonene is one of the most abundant biogenic volatile organic compounds emitted by plants, we hypothesized that urinary metabolites of inhaled limonene can serve as biomarkers of exposure to greenness. To test our hypothesis, we analyzed urine samples collected from eight human volunteers after limonene inhalation or after greenness exposure using liquid chromatography-high resolution mass spectrometry-based profiling. Eighteen isomers of nine metabolites were detected in urine after limonene inhalation, and their kinetic parameters were estimated using nonlinear mixed effect models. Urinary levels of most abundant limonene metabolites were elevated after brief exposure to a forested area, and the ratio of urinary limonene metabolites provided evidence of recent exposure. The identities and structures of these metabolites were validated using stable isotope tracing and tandem mass spectral comparison. Together, these data suggest that urinary metabolites of limonene, especially uroterpenol glucuronide and dihydroperillic acid glucuronide, could be used as individualized biomarkers of greenness exposure. [Display omitted] •UPLC-QTOF-MS was used to measure urinary metabolites of limonene.•Eighteen human urinary metabolites were found and characterized.•Top three compounds elevated after exposure; their ratio indicates recent exposure.•Those 3 metabolites can serve as biomarkers of individual exposure to greenness.•They can complement other study measures to describe effects of vegetation exposure.