Investigations on human biomonitoring for assessing the exposure to synthetic rose oxide in the general population

• Published in: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Vol. 1260; p. 124629
• Main Authors: Tiwald, Carmen, Spindler, Veronika, Scherer, Max, Pluym, Nikola, Peschel, Oliver, Leibold, Edgar, Scherer, Gerhard
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.06.2025
• Subjects: Adult; Biological Monitoring - methods; biomarkers; Biomarkers - urine; body weight; Chiral analysis; chromatography; enantiomers; Environmental Exposure - analysis; environmental monitoring; excretion; Female; Gas Chromatography-Mass Spectrometry - methods; half life; High-resolution mass spectrometry; Human biomonitoring; Humans; hygiene; ionization; laundry; Limit of Detection; Linear Models; Male; mass spectrometry; metabolites; odors; pharmacokinetics; polydimethylsiloxane; Reproducibility of Results; risk; Synthetic rose oxide; temperature; urinalysis; urine; urine collection; Human biomonitoring; Chiral analysis; High-resolution mass spectrometry; Synthetic rose oxide
• ISSN: 1570-0232; 1873-376X; 1873-376X
• DOI: 10.1016/j.jchromb.2025.124629

Rose oxide (RO) is used in cosmetic, hygiene, laundry, cleaning, and household products as a synthetic fragrance. Synthetic rose oxide differs from naturally occurring rose oxide in its enantiomer composition. While natural RO consists mainly of the (−)-cis isomer, synthetic RO contains approximately equal parts of (−)-cis and (+)-cis isomers, as well as small amounts of (−)-trans and (+)-trans isomers. Since in this project, the exposure to industrially produced chemicals by human biomonitoring (HBM) was in the focus, the method development aimed at suitable urinary metabolites derived from the (+)-cis isomer of synthetic RO. For the identification of biomarkers of exposure to synthetic RO as well as for assessing its toxicokinetics, 5 subjects were administered a single oral (0.1 mg/kg body weight) and dermal (0.5 mg/kg) dose of synthetic RO. Analysis of urine fractions by means of high-resolution mass spectrometry (HRMS, conducted with an Orbitrap instrument) revealed that 9-hydroxy-RO (9-OH-RO), 2-hydroxy-4-carboxy-RO (HC-RO), and di-hydroxy-RO and a lactone derived from ring-hydroxylated RO were potential biomarkers of exposure to synthetic RO. Unfortunately, attempts to develop and validate a HBM method for one of these metabolites failed due to insufficient sensitivity (9-OH-RO) or unavailability of standard materials for the required enantiomers (HC-RO, di-OH-RO), lactone). Alternatively, a headspace-solid-phase-micro-extraction-GC–MS (HS-SPME-GC–MS) method for the parent compound (+)-cis-RO was developed and validated. DVB (divinyl benzene)/PDMS (polydimethylsiloxane) fibers suited best for the extraction. Enantiomeric separation was achieved on a Lipodex G column with a temperature gradient. (+)-cis-RO was detected in electron impact ionization (EI) mode. The method performed well with a lower limit of quantification (LLOQ) of 1 ng/L, precision of <10 % and accuracy of >90 %. After oral application, urinary excretion of (+)-cis-RO was fast (mean half-life: 4.1 h) and almost complete after 48 h. However, the mean urinary excretion rate in the 5 subjects amounted to only 7 ppm. (+)-cis-RO was found to be at or slightly above the LLOQ in about half of 14 urine samples from the general population. In conclusion, our investigations for the first time provide data for RO metabolism and toxicokinetics in humans. Despite good to excellent performance, the newly developed and validated HS-SPME-GC–MS method for (+)-cis-RO in urine is only of limited value for HBM of exposure to synthetic RO in the general population, due to the tiny urinary excretion rate of unmetabolized RO and the potential risk of contamination with environmental RO during urine collection and subsequent analytical steps. For a suitable HBM method, potential RO metabolites would need to be synthesized in enantiomerically pure form. Our study provides possible candidates for this approach. •One urinary metabolites of synthetic rose oxide (RO), namely 9- hydroxy-RO, was unambigously identified and three other metabolites were presumptively identified.•These metabolites were potential biomarkers of exposure to synthetic (in contrast to natural) RO in the general population.•Due to current unavailability of enantiopure reference materials, no analytical method for human biomonitoring (HBM) could be developed.•As an alternative, a headspace-solid phase microextraction-GC–MS method targeting (+)-cis-RO in urine was developed and validated.•Despite excellent performance data, this method is of limited value for HBM due to very low urinary excretion rates of unchanged RO and risk of external sample contamination with the parent compound.