Identification of chemicals of emerging concern in urine of Flemish adolescents using a new suspect screening workflow for LC-QTOF-MS.

An essential step in human biomonitoring or molecular epidemiology programs is to estimate human exposure to environmental chemicals. Despite significant progress in the capabilities of analytical methods, the number of pollutants and their metabolites keeps increasing continuously. Some of these relatively unknown chemicals of emerging concern (CECs) may pose significant health risks to humans and biota, but remain virtually undetected in traditional HBM-studies. Non-target and suspect screening techniques based on high-resolution mass spectrometry (HRMS) perform the detection and identification of compounds without any a priori compound selection or chemical information and provide a more holistic overview of human exposure. In this study, 50 urine samples (25 female and 25 male) from a larger cohort of the Flemish Environment and Health Study (FLEHS IV, 2016-2020) have been submitted to suspect screening analysis, with the aim of detecting and identifying new CECs. For this purpose, an analytical method has been developed, optimised and evaluated in terms of analytical performance. Satisfactory results were obtained in terms of reproducibility, sensitivity and quality control. Data-mining was performed through the combination of two different workflows. The use of two complementary workflows enhanced the number of identified compounds. As a result, 45 CECs have been identified with a level of confidence ranged between 3 and 1. Most of the identified compounds were metabolisation products, many of which were currently not included in the targeted measurements of FLEHS IV. The identified chemicals and metabolites could be used as candidate biomarkers of exposure in future studies. Overall, the newly developed suspect screening workflow of this pilot study provided complementary and promising results for future HBM-programs.

Suspect and untargeted screening of bisphenol S metabolites produced by in vitro human liver metabolism.

Bisphenol S (BPS) is increasingly used as substitute for bisphenol A, resulting in higher potential of human exposure to this compound. Yet, information on the human metabolism of BPS is limited. Hence, current biomonitoring studies rely only on the measurement of BPS itself, leading to a potential underestimation of assessing human exposure to this emerging contaminant. The aims of this study were to investigate the in vitro metabolic pathways of BPS using human liver microsomes and cytosol fractions and propose in vitro metabolites for evaluation in pharmacokinetics studies. Liquid chromatography coupled to quadrupole time-of-flight high-resolution mass spectrometry was used for the screening, identification, and structural elucidation of Phase I and II metabolites of BPS for the first time. Metabolite identification was performed using two complementary workflows: suspect and untargeted screening. Two Phase I metabolites were formed through hydroxylation of the phenolic rings. Four Phase II metabolites were formed through conjugation with glucuronic acid or sulfate. Three of these metabolites, namely dihydroxy-BPS, hydroxy-BPS-glucuronide and hydroxy-BPS-sulfate were identified and structurally elucidated for the first time. As such, we provide an expanded set of in vitro biotransformation products of BPS, which can potentially support a reliable assessment of BPS exposure in future biomonitoring studies.