Variability in Background Urinary Concentrations of the Hydrogen Sulfide Biomarker Thiosulfate

Hydrogen sulfide is a toxic gas at high concentrations but has recently attracted attention as a naturally produced gaseous signaling molecule in various tissues of the human body, playing key physiological roles at low nanomolar concentrations. This has wide implications for chronic exposure to this gas in air at low levels far below toxicity. Thiosulfate is the currently used biomarker for exposure to hydrogen sulfide via inhalation but has been mainly employed for acute exposure. It is unknown how background thiosulfate concentrations vary on an intraindividual and interindividual basis in humans at normal ambient hydrogen sulfide levels (<1 μg m^-3), which is key for the interpretation of its levels as biomarker for low-level hydrogen sulfide exposure. In the current work, the variability in thiosulfate urinary excretion in a total of 168 urine samples collected from eight volunteers over a period of 8 weeks was investigated. The determination of thiosulfate in urine was carried out by UHPLC-MS/MS. The total average concentration ± SD was 16 ± 6 μM (n = 168). Average urinary thiosulfate concentrations in the studied volunteers were within the range of 10-20 μM, but it was found that urinary thiosulfate can show significant day-to-day and week-to-week variability in some individuals (up to 10-fold), despite adjusting for urine specific gravity. In light of the presented variability data and previous studies about the lack of consistent response of thiosulfate to low levels of hydrogen sulfide inhalation exposure, and based on a review of the biochemistry of the production of thiosulfate and its various biological sources, it can be argued that thiosulfate might not be suitable as a biomarker for chronic environmental exposure to low levels of hydrogen sulfide via inhalation.