Reference values for urinary 2-phenyl-2-propanol as a biomarker of cumene exposure in a non-occupationally exposed population determined by GC-MS

Background: Cumene is a high-production volume aromatic hydrocarbon recently reclassified as a Category 1B carcinogen, and 2-Phenyl-2-Propanol (2P2P) is its primary urinary metabolite. Highly sensitive analytical methods, required to detect the low-level exposures typical of the non- occupationally exposed general population, are not available for this compound in literature to this day. Research design and methods: This research details the development and validation of a fully automated Gas Chromatography-Mass Spectrometry (GC-MS) method using SPME extraction to quantify 2P2P at ng/L levels. Results: The study established reference values by analyzing 242 non-exposed workers, yielding a background range of 31.6–652.7 ng/L (5th–95th percentiles). The literature review encompassed global production trends, environmental ubiquity, and human metabolism. Furthermore, the study utilized biomarkers like cotinine and S-Phenyl Mercapturic Acid (SPMA) to statistically evaluate smoking as a potential confounder. Conclusion: This method fills a significant technical gap by providing a noninvasive, highly sensitive tool for health surveillance. Establishing empirical background reference values is essential for accurately distinguishing between environmental and occupational exposure. Critically, statistical analysis confirms that cigarette smoking is not a significant confounding factor for urinary 2P2P levels, reinforcing its reliability as a specific biomarker for cumene.