Exposure to benzotriazoles and benzothiazoles in Czech male population and its associations with biomarkers of liver function, serum lipids and oxidative stress.

INTRODUCTION: Benzotriazoles and benzothiazoles (BTs) are high-production volume chemicals as well as widely distributed emerging pollutants with potential health risk. However, information about human exposure to BTs and associated health outcomes is limited. OBJECTIVE: We aimed to characterise exposure to BTs among Czech men, including possible occupational exposure among firefighters, its predictors, and its associations with liver function, serum lipids and oxidative stress. METHODS: 165 participants (including 110 firefighters) provided urine and blood samples that were used to quantify the urinary levels of 8 BTs (high-performance liquid chromatography-tandem mass spectrometry), and 4 liver enzymes, cholesterol, low-density lipoprotein, and 8-hydroxy-2'-deoxyguanosine. Linear regression was used to assess associations with population characteristics and biomarkers of liver function, serum lipids and oxidative stress. Regression models were adjusted for potential confounding variables and false discovery rate procedure was applied to account for multiplicity. RESULTS: The BTs ranged from undetected up to 46.8 ng/mL. 2-hydroxy-benzothiazole was the most predominant compound (detection frequency 83%; median 1.95 ng/mL). 1-methyl-benzotriazole (1M-BTR) was measured in human samples for the first time, with a detection frequency 77% and median 1.75 ng/mL. Professional firefighters had lower urinary 1M-BTR compared to non-firefighters. Urinary 1M-BTR was associated with levels of γ-glutamyl transferase (ß = - 17.54%; 95% CI: - 26.127, - 7.962). CONCLUSION: This is the first study to investigate BT exposure in Central Europe, including potentially exposed firefighters. The findings showed a high prevalence of BTs in the study population, the relevance of 1M-BTR as a new biomarker of exposure, and an urgent need for further research into associated adverse health outcomes.

Firefighters and the liver: Exposure to PFAS and PAHs in relation to liver function and serum lipids (CELSPAC-FIREexpo study).

INTRODUCTION: Firefighting is one of the most hazardous occupations due to exposure to per- and polyfluoroalkyl substances (PFAS) and polycyclic aromatic hydrocarbons (PAHs). Such exposure is suspected to affect the cardiometabolic profile, e.g., liver function and serum lipids. However, only a few studies have investigated the impact of this specific exposure among firefighters. METHODS: Men included in the CELSPAC-FIREexpo study were professional firefighters (n = 52), newly recruited firefighters in training (n = 58), and controls (n = 54). They completed exposure questionnaires and provided 1-3 samples of urine and blood during the 11-week study period to allow assessment of their exposure to PFAS (6 compounds) and PAHs (6 compounds), and to determine biomarkers of liver function (alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin (BIL)) and levels of serum lipids (total cholesterol (CHOL), low-density lipoprotein cholesterol (LDL) and triglycerides (TG)). The associations between biomarkers were investigated both cross-sectionally using multiple linear regression (MLR) and Bayesian weighted quantile sum (BWQS) regression and prospectively using MLR. The models were adjusted for potential confounders and false discovery rate correction was applied to account for multiplicity. RESULTS: A positive association between exposure to PFAS and PAH mixture and BIL (ß = 28.6%, 95% CrI = 14.6-45.7%) was observed by the BWQS model. When the study population was stratified, in professional firefighters and controls the mixture showed a positive association with CHOL (ß = 29.5%, CrI = 10.3-53.6%) and LDL (ß = 26.7%, CrI = 8.3-48.5%). No statistically significant associations with individual compounds were detected using MLR. CONCLUSIONS: This study investigated the associations between exposure to PFAS and PAHs and biomarkers of cardiometabolic health in the Czech men, including firefighters. The results suggest that higher exposure to a mixture of these compounds is associated with an increase in BIL and the alteration of serum lipids, which can result in an unfavourable cardiometabolic profile.

The exposure of Czech firefighters to perfluoroalkyl substances and polycyclic aromatic hydrocarbons: CELSPAC - FIREexpo case-control human biomonitoring study.

The CELSPAC - FIREexpo biomonitoring study investigates the long-term effects of chemical exposure on firefighters' wellness and fitness. It aims to provide science-based measures to minimize the health risks of the firefighting occupation. Here, we present the study design, cohort profile, and first results with respect to internal per- and polyfluoroalkyl substances (PFAS) and polycyclic aromatic hydrocarbons (PAH) levels in study participants. Participants (n = 166) were divided into three subcohorts: i) newly recruited firefighters, ii) professional firefighters with several years' experience, and iii) the control group. Participants underwent physical performance tests, provided information on their lifestyle and diet, and urine and blood samples 1-4 times within an 11-week period. 12 serum PFAS and 10 urinary hydroxylated PAH (OH-PAH) levels were determined using HPLC-MS/MS and compared between subcohorts and samplings. The association of internal exposure with reported lifestyles and occupational factors was investigated using Spearman's correlation, principal component analysis, and multivariate regression analysis. ΣPFAS levels in firefighters were significantly higher than in the control group and were mostly associated with the length of firefighting career, age, blood donation, and population size. 10.9 % and 7.6 % of measurements exceeded the HBM-I or HBM-II value for PFOS and PFOA, respectively. Urinary ΣPAH levels increased significantly after training with burning wooden pallets, but none of them exceeded the no observed genotoxic effect level. Firefighters' occupational exposure, its sources, and pathways, need to be systematically monitored and investigated on a long-term and individual basis. The CELSPAC - FIREexpo study helps to clarify the degree of occupational exposure to the given compounds and the subsequent risks to firefighters.

Identification of Real-Life Mixtures Using Human Biomonitoring Data: A Proof of Concept Study.

Human health risk assessment of chemical mixtures is complex due to the almost infinite number of possible combinations of chemicals to which people are exposed to on a daily basis. Human biomonitoring (HBM) approaches can provide inter alia information on the chemicals that are in our body at one point in time. Network analysis applied to such data may provide insight into real-life mixtures by visualizing chemical exposure patterns. The identification of groups of more densely correlated biomarkers, so-called "communities", within these networks highlights which combination of substances should be considered in terms of real-life mixtures to which a population is exposed. We applied network analyses to HBM datasets from Belgium, Czech Republic, Germany, and Spain, with the aim to explore its added value for exposure and risk assessment. The datasets varied in study population, study design, and chemicals analysed. Sensitivity analysis was performed to address the influence of different approaches to standardise for creatinine content of urine. Our approach demonstrates that network analysis applied to HBM data of highly varying origin provides useful information with regards to the existence of groups of biomarkers that are densely correlated. This information is relevant for regulatory risk assessment, as well as for the design of relevant mixture exposure experiments.

Dynamics of PCB exposure in the past 50 years and recent high concentrations in human breast milk: Analysis of influencing factors using a physiologically based pharmacokinetic model.

In this study we reconstruct the long-term exposure of Czech mothers to polychlorinated biphenyls (PCBs) and determine the causes of high contamination of breast milk by indicator PCBs (iPCBs). A data set containing information from more than 1000 primiparous women from the Czech Republic was used, including iPCB concentrations in breast milk, individual physiology and living characteristics. The time series of PCB intakes for the whole period from the beginning of PCB production in 1958 until 2011 were reconstructed. We estimated the individual lifetime exposure of mothers for all iPCBs, i.e. congeners 28, 52, 101, 118, 138, 153 and 180, using a physiologically based pharmacokinetic (PBPK) model. Various model scenarios were investigated to determine the influence of physiology, age at delivery, past dietary exposure, and food composition on concentrations in breast milk for all iPCBs. The highest contributions to the presence of iPCBs in breast milk were observed for food composition. The main factor determining the concentration of higher-chlorinated PCBs (138, 153 and 180) was past exposure. The most important parameter for identification of children's postnatal exposure through breast milk was the time-span from the maximum of the exposure peak to the birth of the child. The current concentrations of iPCBs in breast milk in the Czech population are still high because the maximum of the exposure peak occurred more than 10 years later than in other European countries and was very broad, e.g. covered more than 10 years.