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 (β = - 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.

• Keywords
• Benzothiazole, Benzotriazole, Human biomonitoring, Liver function, Oxidative stress, Serum lipids,
• MeSH
• 8-Hydroxy-2'-Deoxyguanosine urine   blood   MeSH
• Benzothiazoles * MeSH
• Biomarkers * blood   urine   MeSH
• Cholesterol blood   MeSH
• Deoxyguanosine analogs & derivatives   urine   blood   MeSH
• Adult MeSH
• Firefighters MeSH
• Liver drug effects   MeSH
• Middle Aged MeSH
• Humans MeSH
• Lipids blood   MeSH
• Oxidative Stress * drug effects   MeSH
• Occupational Exposure * analysis   MeSH
• Triazoles * MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH
• Names of Substances
• 8-Hydroxy-2'-Deoxyguanosine MeSH
• Benzothiazoles * MeSH
• benzotriazole MeSH Browser
• Biomarkers * MeSH
• Cholesterol MeSH
• Deoxyguanosine MeSH
• Lipids MeSH
• Triazoles * MeSH

Current-use pesticide (CUP) exposure occurs mainly through diet and environmental application in both agricultural and urban settings. While pesticide exposure has been associated with many adverse health outcomes, the intermediary molecular mechanisms are still not completely elucidated. Among others, their roles in epigenetics (DNA methylation) and DNA damage due to oxidative stress are presumed. Scientific evidence on urinary biomarkers of such body response in general population is limited, especially in children. A total of 440 urine samples (n = 110 parent-child pairs) were collected during the winter and summer seasons in order to describe levels of overall DNA methylation (5-mC, 5-mdC, 5-hmdC, 7-mG, 3-mA) and oxidative stress (8-OHdG) biomarkers and investigate their possible associations with metabolites of pyrethroids (3-PBA, t/c-DCCA), chlorpyrifos (TCPY), and tebuconazole (TEB-OH). Linear mixed-effects models accounting for intraindividual and intrahousehold correlations were utilized. We applied false discovery rate procedure to account for multiplicity and adjusted for potential confounding variables. Higher urinary levels of most biological response biomarkers were measured in winter samples. In adjusted repeated measures models, interquartile range (IQR) increases in pyrethroid metabolites were associated with higher oxidative stress. t/c-DCCA and TCPY were associated with higher urinary levels of cytosine methylation biomarkers (5-mC and/or 5-mdC). The most robust association was observed for tebuconazole metabolite with 3-mA (-15.1% change per IQR increase, 95% CI = -23.6, -5.69) suggesting a role of this pesticide in reduced demethylation processes through possible DNA glycosylase inhibition. Our results indicate an urgent need to extend the range of analyzed environmental chemicals such as azole pesticides (e.g. prothioconazole) in human biomonitoring studies. This is the first study to report urinary DNA methylation biomarkers in children and associations between CUP metabolites and a comprehensive set of biomarkers including methylated and oxidized DNA alterations. Observed associations warrant further large-scale research of these biomarkers and environmental pollutants including CUPs.

• Keywords
• Current-use pesticides (CUPs), DNA methylation, Epigenetics, Oxidative stress, Urine,
• MeSH
• Biomarkers metabolism   MeSH
• Adult MeSH
• Humans MeSH
• DNA Methylation MeSH
• Oxidative Stress MeSH
• Pesticides * analysis   MeSH
• Pyrethrins * urine   MeSH
• Environmental Exposure analysis   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Czech Republic MeSH
• Names of Substances
• Biomarkers MeSH
• Pesticides * MeSH
• Pyrethrins * MeSH