Human Biomonitoring of the fragrant compound Geraniol - The challenge of exposure assessment of natural products and nature-identical chemicals

摘要

Accident Insurance, Institute of the Ruhr University Bochum, Bochum, Germany Michael Bader, BASF SE, Ludwigshafen, Germany Geraniol is a fragrant compound with a rose-like smell, and is versatilely utilized in cosmetic and hygiene products as well as in household cleaners. The annual worldwide use exceeds 1,000 metric tons. For this purpose, geraniol is either extracted from essential oils (natural product) or is chemically synthesized (natural-identical flavouring) on an industrial scale. Within a collaboration project between the German Chemical Industry Association (VCI) and the German Federal Ministry for the Environment, Nature Conservation, Building and Nuclear Safety (BMUB), an analytical method for the determination of geraniol metabolites in human urine was developed. In addition, a volunteer study was carried out in order to investigate the human metabolism of geraniol. A method was developed and validated for the analysis of the main urinary metabolites of geraniol, namely Hildebrandt acid, 8-carboxygeraniol, geranic acid and 3-hydroxycitronellic acid. Sample preparation involves enzymatic hydrolysis and liquid-liquid extraction. The analyses are carried out by liquid chromatography with tandem mass spectrometry (LC-MS/MS) which offers a sensitive and specific quantification of the four metabolites. The volunteer study showed that a large percentage of the administered geraniol is metabolized to urinary eliminated Hildebrandt acid, geranic acid and 3-hydroxycitronellic acid. 8-Carboxygeraniol is only a minor metabolite (<2 % of the dose). However, it seems to be a specific biomarker for geraniol while the other metabolites may have different precursors, e.g. citral. The elimination of all metabolites was fast, with peak concentrations at 1.5 - 5 hours after oral ingestion and subsequent elimination half-lives of 2 - 5 hours. In the course of the method validation, background values of all metabolites were detected in spot urine samples of persons without occupational exposure to geraniol. In conclusion, the novel analytical method enables the determination of 8-carboxygeraniol, Hildebrandt acid, geranic acid and 3-hydroxycitronellic acid in human urine. 8-Carboxygeraniol seems to be a specific and thus promising biomarker for geraniol exposure. The application of the method to samples of the general population, together with the results of the metabolism study may assist in the exposure assessment and evaluation of the daily uptake of geraniol by food and/or consumer products.