Search

This study aims to develop and validate a robust analytical method for the quantification of polybrominated diphenyl ethers (PBDEs) in human serum using gas chromatography–tandem mass spectrometry. We compared procedural blanks, recoveries, and operational convenience of liquid–liquid extraction and supported liquid extraction for the determination of serum PBDEs. We evaluated different extraction solvents for their effect on PBDE recoveries. Supported liquid extraction was selected for method validation due to its operational convenience. The method demonstrated satisfactory linearity, sensitivity, and reproducibility, with the range of 0.10–5.00 µg/L for most PBDE congeners and 0.20–10.0 µg/L for PBDE‐154 and PBDE‐183, with limits of detection ranging from 2 to 48 ng/L, and with matrix effects ranging from 94% to 113%. Quality control assessments indicated that recoveries ranged from 85% to 110% and relative standard deviations of less than 11%. The proposed method was applied to biomonitoring of 111 healthy adults, revealing detectable levels of PBDEs in over 90% of the samples. BDE‐47 and BDE‐183 were the most prevalent, with mean concentrations of 4.13 and 22.1 ng/L, respectively. Detection frequencies ranged from 0.90% for BDE‐17 and BDE‐85 to 25.2% for BDE‐47. Males had higher mean concentrations of BDE‐183 than females. [ABSTRACT FROM AUTHOR]

Per- and polyfluoroalkyl substances (PFAS) are known as persistent and bioaccumulative chemicals. The present paper describes the analysis of 969 human blood samples collected in South Germany aiming to determine whether there are statistic significant differences in internal PFAS burden between three regions with known PFAS releases in the environment (study regions) and three regions without known PFAS releases in the environment (control regions). Nine environmental relevant PFAS were analyzed, including the perfluorooctanoic acid (PFOA) substitute 3H-perfluoro-3-[(3-methoxy-propoxy)propanoic acid] ammonium salt (ADONA). We found that concentrations of PFOA and perfluorooctane sulfonate (PFOS) were higher than for all other PFAS in all of the six regions, but all medians of PFOA (between 0.8 and 0.9 ng/ml for the study and control regions) and PFOS (between 1.3 and 1.5 ng/ml for the study regions and between 1.4 and 1.5 ng/ml for the control regions) were below the human biomonitoring values (HBM) I for PFOA (2 ng/ml) und for PFOS (5 ng/ml) derived by the German HBM Commission. Concentrations of ADONA were below the limit of quantification in all samples. Minor differences were observed in PFAS blood levels between study and control regions. Especially for PFOS and PFOA the medians for women are slightly lower compared to men. In summary, individuals living in regions with known environmental PFAS contaminations show no higher internal PFAS exposure to controls and in comparison to other studies in the literature. [ABSTRACT FROM AUTHOR]

Trace elements (TEs) are ubiquitous. TE concentrations vary among individuals and countries, depending on factors such as living area, workplaces and diet. Deficit or excessive TEs concentrations have consequences on the proper functioning of human organism so their biomonitoring is important. The aim of this project was to provide reference values for TEs concentrations in the Swiss population. The 1,078 participants to the SKiPOGH cohort included in this study were aged 18–90 years. Their 24-h urine and/or plasma samples were analyzed by inductively coupled plasma mass spectrometry (ICP-MS) to determine 24 TEs concentrations: Ag, Al, As, Be, Bi, Cd, Co, Cr, Cu, Hg, I, Li, Mn, Mo, Ni, Pb, Pd, Pt, Sb, Se, Sn, Tl, V and Zn. Statistical tests were performed to evaluate the influence of covariates (sex, age, BMI, smoking) on these results. Reference intervals for the Swiss adult population were also defined. TEs concentrations were obtained for respectively 994 and 903 persons in plasma and urine matrices. It was possible to define percentiles of interest (P50 and P95) for almost all the TEs. Differences in TEs distribution between men and women were noticed in both matrices; age was also a cofactor. This first Swiss biomonitoring of a large TEs-panel offers reference values in plasma and in urine for the Swiss population. The results obtained in this study were generally in line with clinical recommendations and comparable to levels reported in other population-based surveys. [ABSTRACT FROM AUTHOR]

The chemical UV filter 2-ethylhexyl salicylate (EHS) is used in various personal-care products. The dermal and oral metabolism of EHS have already been targeted by different studies. However, toxicokinetic data after a single dermal exposure to EHS was missing. In our study, three volunteers were dermally exposed to a commercial EHS-containing sunscreen for 9 h with an application dose of 2 mg sunscreen per cm2 body surface area. The exposure was performed indoors, and sunscreen was applied on about 75% of the total skin area. Complete urine voids were collected over 72 h and eight blood samples were drawn from each subject. Urine samples were analyzed for EHS and seven known metabolites (5OH-EHS, 4OH-EHS, 2OH-EHS, 6OH-EHS, 4oxo-EHS, 5oxo-EHS, and 5cx-EPS) by online-SPE UPLC MS/MS. The peaks of urinary elimination occurred 10–11 h after application. The elimination half-lives (Phase 1) were between 6.6 and 9.7 h. The dominant urinary biomarkers were EHS itself, followed by 5OH-EHS, 5cx-EPS, 5oxo-EHS, and 4OH-EHS. 2OH-EHS, 6OH-EHS, and 4oxo-EHS were detected only in minor amounts. An enhanced analysis of conjugation species revealed marginal amounts of unconjugated metabolites and up to 40% share of sulfate conjugates for 5OH-EHS, 5oxo-EHS, and 5cx-EPS. The results demonstrated a delayed systemic resorption of EHS via the dermal route. Despite an extensive metabolism, the parent compound occurred as main urinary parameter. The delayed dermal resorption as well as the slow elimination of EHS indicate an accumulation up to toxicological relevant doses during daily repeated dermal application to large skin areas. [ABSTRACT FROM AUTHOR]

The use of the comet assay in large biomonitoring studies may present logistical and technical challenges because of the processing of numerous samples. Proper sample preservation becomes imperative to prevent spurious DNA breakage. Previous research has shown the feasibility of conducting the comet assay on frozen blood samples, highlighting the potential of freezing at – 80 °C in preserving DNA integrity. Nonetheless, this approach presents challenges, including potential DNA damage during freezing and thawing, variability in processing, and the need for standardized protocols. Our objective was to evaluate whether there are comparable results in DNA migration assessed by the comet assay between fresh and frozen blood samples on a larger scale (N = 373). In our findings, elevated DNA migration was evident in frozen samples relative to fresh ones. Additionally, smoking, alcohol consumption, and season were linked to increased DNA damage levels in whole blood cells. Based on our results and available literature, conducting the comet assay on frozen blood samples emerges as a practical and efficient approach for biomonitoring and epidemiological research. This method enables the assessment of DNA damage in large populations over time, with samples, if properly cryopreserved, that may be used for years, possibly even decades. These observations hold significant implications for large-scale human biomonitoring and long-term epidemiological studies, particularly when samples are collected during fieldwork or obtained from biobanks. Continued method optimization and validation efforts are essential to enhance the utility of this approach in environmental and occupational health studies, emphasizing caution when comparing data obtained between fresh and frozen blood samples. [ABSTRACT FROM AUTHOR]

2-Ethylhexyl salicylate (EHS) is an organic UV filter which is used in sunscreen and other personal care products. The dermal uptake of EHS was studied in several dermal-exposure experiments. This paper aims to coherently assess urine samples after dermal exposure for the biomarkers EHS, 5OH-EHS, 5oxo-EHS, and 5cx-EPS as well as further biomarkers of interest, specifically 4OH-EHS, 4oxo-EHS, 2OH-EHS, and 6OH-EHS, for the first time. Samples from 18 participants of a pre-existing dermal exposure study under real-life conditions were reassessed using a comprehensive LC-MS/MS method. EHS accounts for 34 % of the cumulative excretion of all analytes within 24 h after exposure, followed by 5OH-EHS (19 %), 5cx-EPS (18 %), 4OH-EHS (15 %) and 5oxo-EHS (11 %). Further metabolites were only quantified in minor amounts. EHS as the most prominent excretion parameter in this study demonstrates the missing first-pass effect after dermal absorption. Furthermore, the applied novel comprehensive analytical procedure revealed oxidation at the ω (5cx-EPS, 6OH-EHS), ω-1 (5OH-EHS, 5oxo-EHS), and ω-2 positions (4OH-EHS, 4oxo-EHS) in the main chain of the ethylhexyl group as well as oxidation in the side chain (2OH-EHS). The presented data are of high relevance for a reliable toxicological risk assessment of dermal exposure to EHS. [Display omitted] • Toxicokinetic assessment of 2-ethylhexy salicylate (EHS) and metabolites. • Real-life dermal exposure scenario. • Confirming EHS, 5OH-EHS, 5oxo-EHS and 5cx-EPS as relevant biomarkers. • Showing relevant oxidation at ω, ω-1, ω-2 position in the ethylhexyl chain. • Formation of considerable amounts of 4OH-EHS after dermal exposure to EHS. [ABSTRACT FROM AUTHOR]

• Non-ferrous metals smelting workers had higher urinary metal(loid)s levels. • Workers co-exposed to arsenic, cadmium, lead, antimony, thallium and tin from smelting. • Workers had the lowest arsenic methylation capacity, followed by residents. • Residents living closer to the smelting plant suffered higher health risks. Non-ferrous metal smelting poses significant risks to public health. Specifically, the copper smelting process releases arsenic, a semi-volatile metalloid, which poses an emerging exposure risk to both workers and nearby residents. To comprehensively understand the internal exposure risks of metal(loid)s from copper smelting, we explored eighteen metal(loid)s and arsenic metabolites in the urine of both occupational and non-occupational populations using inductively coupled plasma mass spectrometry with high-performance liquid chromatography and compared their health risks. Results showed that zinc and copper (485.38 and 14.00 µg/L), and arsenic, lead, cadmium, vanadium, tin and antimony (46.80, 6.82, 2.17, 0.40, 0.44 and 0.23 µg/L, respectively) in workers (n =179) were significantly higher compared to controls (n =168), while Zinc, tin and antimony (412.10, 0.51 and 0.15 µg/L, respectively) of residents were significantly higher than controls. Additionally, workers had a higher monomethyl arsenic percentage (MMA%), showing lower arsenic methylation capacity. Source appointment analysis identified arsenic, lead, cadmium, antimony, tin and thallium as co-exposure metal(loid)s from copper smelting, positively relating to the age of workers. The hazard index (HI) of workers exceeded 1.0, while residents and control were approximately at 1.0. Besides, all three populations had accumulated cancer risks exceeding 1.0 × 10−4, and arsenite (AsIII) was the main contributor to the variation of workers and residents. Furthermore, residents living closer to the smelting plant had higher health risks. This study reveals arsenic exposure metabolites and multiple metals as emerging contaminants for copper smelting exposure populations, providing valuable insights for pollution control in non-ferrous metal smelting. [Display omitted] [ABSTRACT FROM AUTHOR]

Organophosphate flame retardants (OPFRs) are widely used as substitutes for traditional brominated flame retardants, necessitating a reliable and sensitive method for biomonitoring their urinary metabolites to assess human exposure. This study conducted biomonitoring of 10 metabolites of OPFRs in 152 adults and assessed their association with oxidative stress biomarkers 8-hydroxydeoxyguanosine and 8-hydroxyguanosine. Urinary metabolites of OPFRs were released via enzymatic deconjugation. The addition of sodium chloride to the urine samples increases the ionic strength, inducing a salting-out effect that reduces the solubility of these compounds, thereby facilitating their extraction with a mixture of ethyl acetate and acetonitrile. Then, the metabolites of OPFRs were quantified by ultra-high performance liquid chromatography-tandem mass spectrometry, and we validated the method for linear range, precision, matrix effect, and method detection limit. The detection limit of the metabolites of OPFRs ranged from 0.01 to 0.2 μg/L, and these metabolites were detected with high frequencies ranging from 25.0 to 98.68% in the urine samples. The concentration of bis (2-chloroethyl) phosphate was significantly higher in males than in females, with the geometric mean concentration of 0.88 μg/L for males and 0.53 μg/L for females, respectively. Spearman correlation analysis revealed weak but statistically significant positive correlations among the urinary metabolites. Bayesian kernel machine regression analysis showed a significant positive association between elevated urinary concentrations of metabolites of OPFRs and increased oxidative stress levels. Di-n-butyl phosphate was identified as the metabolite that significantly contributed to the elevated level of 8-hydroxyguanosine. [ABSTRACT FROM AUTHOR]

Bisphenols are widely used as monomers and additives in plastic production. Thus, bisphenol A (BPA) and its most prominent substitutes have been detected in many environmental and human samples. This study proposes an online solid-phase extraction analytical methodology coupled to liquid chromatography with tandem mass spectrometry for the determination of six bisphenols (BPA and bisphenols F (BPF), S (BPS), AF (BPAF), B (BPB), and E (BPE)) in urine samples as an efficient and automated methodology. The method was developed and validated for all bisphenols with good recoveries (92–112%) and repeatability (RSD ≤ 10%) despite the variable matrix effects, except BPAF (which would require a dedicated internal standard), achieving method quantification limits in the 0.05–2.2 ng mL−1 range. The methodology was subsequently applied to 435 urine samples from a non-occupational exposure population (civil servants for the regional government) from Santiago de Compostela (Galicia, Spain). Only BPA, BPF, and BPS were positively detected; the last two presented higher detection frequencies than BPA. When the urinary concentrations are extrapolated to human intake and compared to the European Food Safety Agency (EFSA) tolerable daily intake (TDI) of 2 × 10−4 µg kg−1 day−1 (TDI), all BPA positively identified samples would surpass this threshold. Although no TDI exists currently for the other two identified bisphenols, it is evident that human exposure to bisphenols should be limited. Finally, the results stratification by gender revealed higher levels of exposure to BPF in the women group. [ABSTRACT FROM AUTHOR]

Since the launch of the Chemicals Management Plan (CMP) in 2006, Health Canada has initiated screening-level risk assessments (RAs) of approximately 4300 priority substances under the Canadian Environmental Protection Act , 1999 (CEPA). With the availability of nationally representative human biomonitoring (HBM) data, over 300 of these substances were assessed using HBM-based RA approaches. Qualitative and quantitative HBM-based RA approaches for the regulatory risk assessment of the general population of Canada were developed to increase the efficiency of screening the potential health risk of CMP priority substances. To support HBM-based RAs, several biomonitoring equivalents (BE) were derived to interpret HBM data. For some CMP substances, Health Canada conducted cumulative risk assessments of chemical mixtures using HBM data as measures of exposure. In 2023, CEPA was amended to include the assessment of populations who may be disproportionately impacted (vulnerable populations) and the cumulative effects of multiple chemicals. Going forward, Health Canada is exploring modern approaches in HBM-based RAs, including biomarkers of effect and non-traditional biomarkers (e.g., hair, nails) to address CEPA amendments. This manuscript will discuss Health Canada's progress in HBM-based RAs, and the possible path forward in using HBM data to strengthen human health risk assessments. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Mycotoxins, natural toxins produced by fungi, contaminate nearly 80% of global food crops. Alternaria mycotoxins, including alternariol (AOH), alternariol monomethylether (AME), and tenuazonic acid (TeA), present a health concern due to their prevalence in various plants and fruits. Exposure to these toxins exceeds the threshold of toxicological concern in some European populations, especially infants and toddlers. Despite this, regulatory standards for Alternaria toxins remain absent. The lack of toxicokinetic parameters, reference levels, and sensitive detection methods complicates risk assessment and highlights the necessity for advanced biomonitoring (HBM) techniques. This study addresses these challenges by developing and validating ultra-high performance liquid chromatography method coupled with tandem mass spectrometry to quantify AOH, AME, TeA, and their conjugates in multiple biological matrices. The validated method demonstrates robust linearity, precision, recovery (94–111%), and sensitivity across urine (LOD < 0.053 ng/mL), capillary blood (LOD < 0.029 ng/mL), and feces (LOD < 0.424 ng/g), with significantly lower LOD for TeA compared to existing methodologies. The application of minimally invasive microsampling techniques for the blood collection enhances the potential for large-scale HBM studies. These advancements represent a step toward comprehensive HBM and exposure risk assessments for Alternaria toxins, facilitating the generation of data for regulatory authorities. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous pollutants of significant public health concern, with several that are highly toxic to humans, including some proven or suspected carcinogens. To account for the high variability of PAH mixtures encountered in occupational settings, adjusting urinary 1-hydroxypyrene (1-OHP) levels by the total airborne pyrene (PyrT)/benzo[a]pyrene (BaP) ratio is essential for human biomonitoring (HBM). Given the complexity and cost of systematically monitoring atmospheric levels, alternative approaches to simultaneous airborne and HBM are required. The aim of this review was to catalog airborne PyrT/BaP ratios measured during different industrial activities and recommend 1-OHP-dedicated biological guidance values (BGV). A literature search was conducted. Seventy-one studies were included, with 5619 samples pertaining to 15 industrial sectors, 79 emission processes, and 213 occupational activities. This review summarized more than 40 years of data from almost 20 countries and highlighted the diversity and evolution of PAH emissions. PyrT/BaP ratios were highly variable, ranging from 0.8 in coke production to nearly 40 in tire and rubber production. A single PyrT/BaP value cannot apply to all occupational contexts, raising the question of the relevance of defining a single biological limit value for 1-OHP in industrial sectors where the PyrT/BaP ratio variability is high. Based upon the inventory, a practical approach is proposed for systematic PAH exposure and risk assessment, with a simple frame to follow based upon specific 1-OHP BGVs depending upon the occupational context and setup of a free PAH HBM interactive tool. [ABSTRACT FROM AUTHOR]

For the investigation of diseases and other harmful environmental influences (e.g., chemicals) epidemiological studies rely on high quality human samples, among others. Collecting samples and data in the field can pose an enormous challenge to the study team with regard to health protection and occupational safety, especially in the context of a pandemic where there was great uncertainty about the biological risks associated with SARS-CoV-2. The German Environmental Specimen Bank (German ESB) is a key element of environmental and human biomonitoring in Germany with the aim to document and assess trends of human and environmental exposure to chemicals over time and to provide scientific data for policy decision makers. Starting with a pilot study in 1978 human samples are now collected at four sampling locations annually, while sampling is carried out with a highly standardized mobile laboratory since 2013. Due to the corona pandemic 3 of 4 ESB sampling campaigns had to be cancelled in 2020. However, a continuous sampling is crucial to generate current policy relevant data on chemical exposure. Hence, a protection and hygiene concept has been developed including COVID-19 testing with the goal to protect the health of participants and employees during sampling and to meet legal requirements, while sustaining the standardized procedures of sampling and sample preparation. The concept is based on a flexible approach to allow adjustments to changing government regulations and recommendations in the course of the pandemic. By implementing this concept, all samplings were successfully carried out in 2021 & 2022, with the pandemic still ongoing. This paper provides an example of good practice and valuable insights in how to collect human samples during a pandemic. • Conducting epidemiological sampling and data collection for the German Environmental Specimen Bank during a pandemic. • Risk Assessment & development of an infection protection & hygiene concept to conduct safe sampling in a mobile laboratory. • Rapid sample handling, Point-of-Care analytics, and on-site cryopreservation. • Lessons learned during Covid 19 epidemic for future pandemic situations. [ABSTRACT FROM AUTHOR]

Globin adducts of various chemicals, persisting in organism over the whole lifetime of erythrocytes, have been used as biomarkers of cumulative exposures to parent compounds. After removal of aged erythrocytes from the bloodstream, cleavage products of these adducts are excreted with urine as alternative, non-invasively accessible biomarkers. In our biomonitoring studies on workers exposed to ethylene oxide, its adduct with globin, N -(2-hydroxyethyl)valine, and the related urinary cleavage product N -(2-hydroxyethyl)-L-valyl-L-leucine have been determined. To describe a toxicokinetic relationship between the above types of biomarkers, a general compartmental model for simulation of formation and removal of globin adducts has been constructed in the form of code in R statistical computing environment. The essential input variables include lifetime of erythrocytes, extent of adduct formation following a single defined exposure, and parameters of exposure scenario, while other possible variables are optional. It was shown that both biomarkers reflect the past exposures differently as the adduct level in globin is a mean value of adduct levels across all compartments (subpopulations of erythrocytes of the same age) while excretion of cleavage products reflects the adduct level in the oldest compartment. Application of the model to various scenarios of continuous exposure demonstrated its usefulness for human biomonitoring data interpretation. • Compartmental model to simulate formation and elimination of adducts with globin. • Toxicokinetics of the adducts in globin and their cleavage products in the urine. • Non-invasive biomonitoring to assess long-term exposures to electrophilic chemicals. [ABSTRACT FROM AUTHOR]

Mycotoxins are toxic secondary metabolites produced by various fungi that can contaminate food crops, which, in turn, may lead to human exposure. Chronic exposure to mycotoxins can cause adverse health effects including reproductive and developmental toxicity. Pregnant women and their foetuses present a vulnerable group for exposure to mycotoxins that can cross the placenta. Human biomonitoring of mycotoxins provides a real-life approach to estimate internal exposure. In this pilot study, 24-h urine samples from 36 pregnant Dutch women were analysed for aflatoxin M1 (AFM1), total deoxynivalenol (DON), de-epoxy-deoxynivalenol (DOM-1), total zearalenone (ZEN), total α-zearalenol (α-ZEL), total β-zearalenol (β-ZEL) and total zearalanone (ZAN), where 'total' refers to mycotoxins and their conjugated forms. Serum samples from these women were analysed for fumonisin B1 (FB1) and ochratoxin A (OTA). All samples were measured using liquid chromatography–tandem mass spectrometry (LC-MS/MS). The most prevalent mycotoxins were total DON, total ZEN and OTA, with a detection frequency of 100%. DOM-1, total α-ZEL and total β-ZEL were detected but to a lesser extent, while AFM1, total ZAN and FB1 were undetected. Median concentrations were 4.75 μg total DON/L, 0.0350 μg DOM-1/L, 0.0413 μg total ZEN/L, 0.0379 μg total α-ZEL/L, 0.0189 μg total β-ZEL/L, and 0.121 μg OTA/L. The calculated median concentration for total ZEN and its metabolites was 0.105 μg/L. Based on two separate risk assessment approaches, total DON exposure in this group was considered to be of low concern. Similarly, exposure to total ZEN and its metabolites in this group was of low concern. For OTA, the risk of non-neoplastic effects was of low concern based on exposure in this group, and the risk of neoplastic effects was of low concern in the majority of participants in this group. The findings of this pilot study confirm the presence of mycotoxins in the urine and serum of pregnant Dutch women, with total DON, total ZEN, and OTA most frequently detected. Exposure to all measured mycotoxins was considered to be of low concern in this group, except for exposure to OTA, which was of low concern for the majority of participants. The study's findings offer valuable insights but should be confirmed using a larger and more diverse sample of the Dutch general population. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous pollutants formed during the incomplete combustion of organic matter such as tobacco. Among these, benzo[a]pyrene (BaP) has been classified as a known carcinogen to humans. It unfolds its effect through metabolic activation to BaP-(7R,8S)-diol-(9S,10R)-epoxide (BPDE), the ultimate carcinogen of BaP. In this article, we describe a simple and highly sensitive GC–NICI–MS/MS method for the quantification of urinary BaP-(7R,8S,9R,10S)-tetrol ((+)-BPT I-1), the hydrolysis product of BPDE. The method was validated and showed excellent results in terms of accuracy, precision, and sensitivity (lower limit of quantification (LLOQ): 50 pg/L). In urine samples derived from users of tobacco/nicotine products and non-users, only consumption of combustible cigarettes was associated with a significant increase in BPT I-1 concentrations (0.023 ± 0.016 nmol/mol creatinine, p < 0.001). Levels of users of potentially reduced-risk products as well as non-users were all below the LLOQ. In addition, the urine levels of six occupationally exposed workers were analyzed and showed the highest overall concentrations of BPT I-1 (844.2 ± 336.7 pg/L). Moreover, comparison with concentrations of 3-hydroxybenzo[a]pyrene (3-OH-BaP), the major detoxification product of BaP oxidation, revealed higher levels of 3-OH-BaP than BPT I-1 in almost all study subjects. Despite the lower levels, BPT I-1 can provide more relevant information on an individual's cancers susceptibility since BPDE is generated by the metabolic activation of BaP. In conclusion, BPT I-1 is a suitable biomarker to distinguish not only cigarette smokers from non-smokers but also from users of potentially reduced-risk products. [ABSTRACT FROM AUTHOR]

Homosalate (HMS) is a UV filter used in sunscreens and personal care products as a mixture of cis- and trans-isomers. Systemic absorption after sunscreen use has been demonstrated in humans, and concerns have been raised about possible endocrine activity of HMS, making a general population exposure assessment desirable. In a previous study, it was shown that the oral bioavailability of cis-HMS (cHMS) is lower than that of trans-HMS (tHMS) by a factor of 10, calling for a separate evaluation of both isomers in exposure and risk assessment. The aim of the current study is the investigation of HMS toxicokinetics after dermal exposure. Four volunteers applied a commercial sunscreen containing 10% HMS to their whole body under regular-use conditions (18–40 mg HMS (kg bw)−1). Parent HMS isomers and hydroxylated and carboxylic acid metabolites were quantified using authentic standards and isotope dilution analysis. Further metabolites were investigated semi-quantitatively. Elimination was delayed and slower compared to the oral route, and terminal elimination half-times were around 24 h. After dermal exposure, the bioavailability of cHMS was a factor of 2 lower than that of tHMS. However, metabolite ratios in relation to the respective parent isomer were very similar to the oral route, supporting the applicability of the oral-route urinary excretion fractions for dermal-route exposure assessments. Exemplary calculations of intake doses showed margins of safety between 11 and 92 (depending on the approach) after single whole-body sunscreen application. Human biomonitoring can reliably quantify oral and dermal HMS exposures and support the monitoring of exposure reduction measures. [ABSTRACT FROM AUTHOR]

Exposure to polyphenols is relevant throughout critical windows of infant development, including the breastfeeding phase. However, the quantitative assessment of polyphenols in human breast milk has received limited attention so far, though polyphenols may positively influence infant health. Therefore, a targeted LC–MS/MS assay was developed to investigate 86 analytes representing different polyphenol classes in human breast milk. The sample preparation consisted of liquid extraction, salting out, freeze-out, and a dilution step. Overall, nearly 70% of the chemically diverse polyphenols fulfilled all strict validation criteria for full quantitative assessment. The remaining analytes did not fulfill all criteria at every concentration level, but can still provide useful semi-quantitative insights into nutritional and biomedical research questions. The limits of detection for all analyzed polyphenols were in the range of 0.0041–87 ng*mL−1, with a median of 0.17 ng*mL−1. Moreover, the mean recovery was determined to be 82% and the mean signal suppression and enhancement effect was 117%. The developed assay was applied in a proof-of-principle study to investigate polyphenols in breast milk samples provided by twelve Nigerian mothers at three distinct time points post-delivery. In total, 50 polyphenol analytes were detected with almost half being phenolic acids. Phase II metabolites, including genistein-7-β-D-glucuronide, genistein-7-sulfate, and daidzein-7-β-D-glucuronide, were also detected in several samples. In conclusion, the developed method was demonstrated to be fit-for-purpose to simultaneously (semi-) quantify a wide variety of polyphenols in breast milk. It also demonstrated that various polyphenols including their biotransformation products were present in breast milk and therefore likely transferred to infants where they might impact microbiome development and infant health. [ABSTRACT FROM AUTHOR]

Metal-based nanomaterials (MNMs) have gained particular interest in nanotechnology industry. They are used in various industrial processes, in biomedical applications or to improve functional properties of several consumer products. The widescale use of MNMs in the global consumer market has resulted in increases in the likelihood of exposure and risks to human beings. Human exposure to MNMs and assessment of their potential health effects through the concomitant application of biomarkers of exposure and effect of the most commonly used MNMs were reviewed in this paper. In particular, interactions of MNMs with biological systems and the nanobiomonitoring as a prevention tool to detect the early damage caused by MNMs as well as related topics like the influence of some physicochemical features of MNMs and availability of analytical approaches for MNMs testing in human samples were summarized in this review. The studies collected and discussed seek to increase the current knowledge on the internal dose exposure and health effects of MNMs, highlighting the advantages in using biomarkers in primary prevention and health surveillance. [ABSTRACT FROM AUTHOR]

The article explores the association between serum levels of per- and polyfluoroalkyl substances (PFASs) and lipid profile, as well as metabolic syndrome in Czech adults, based on data from the HBM-EHES survey 2019. Topics include the detection of six PFASs in serum samples, significant positive associations between certain PFASs and blood cholesterol levels, and the absence of an association between PFASs and metabolic syndrome prevalence.

Glyphosate-based herbicides are the most widely used pesticides in the world; however, the toxicity of glyphosate (GlyP) toward humans, especially its carcinogenicity, is controversial. The aim of this work was to validate a rapid assay for measuring GlyP and its metabolite aminomethylphosphonic acid (AMPA) in urine for human biomonitoring. The analytes were purified via solid-phase extraction in the presence of isotopically labeled internal standards. An LC-MS/MS assay was developed using a column with a novel hybrid stationary phase combined with anion exchange and hydrophilic interaction liquid chromatography. Detection and quantification were performed using negative electrospray ionization in a hybrid triple quadrupole/linear ion trap mass spectrometer. The retention times for AMPA and GlyP were 1.44 and 7.24 min, respectively. Calibration curves showed a linear dynamic range of up to 40 µg/L, inter- and intra-run precisions <7.5%, and accuracies within 10% of the theoretical concentrations. The limits of quantification were 0.1 µg/L and 0.5 µg/L for GlyP and AMPA, respectively. The matrix effect bias was controlled using internal standards. Successful participation in external quality assurance exercises strengthens the validity of the method. The assay was applied to the measurement of GlyP and AMPA in the urine of 9 urban residents, 26 rural residents, and 12 agricultural workers; while AMPA was mostly not quantifiable, the median GlyP values were 0.1 and 0.34 µg/L in rural residents and workers, respectively. The assay is useful to assess GlyP and AMPA in human urine following different exposure scenarios. [ABSTRACT FROM AUTHOR]

2,4,7,9-Tetramethyl-5-decyne-4,7-diol (TMDD) is a non-ionic surfactant with a wide range of applications. TMDD is considered a high-production chemical and, due to its low biodegradation rate, possesses a potentially high prevalence in the environment. However, despite its widespread use, toxicokinetic data and data on internal exposure to TMDD in the general population are completely lacking. Hence, we developed a human biomonitoring (HBM) method for TMDD. Our approach included a metabolism study with four subjects, who were administered an oral dose of 75 µg TMDD/kg body weight and a dermal dose of 750 µg/kg body weight. Terminal methyl-hydroxylated TMDD (1-OH-TMDD) was previously identified as the main urinary metabolite in our lab. The results of the oral and dermal applications were used to determine the toxicokinetic parameters of 1-OH-TMDD as a biomarker of exposure. Finally, the method was applied to 50 urine samples from non-occupationally exposed volunteers. Results show that TMDD was rapidly metabolized, with an average tmax of 1.7 h and a rapid and almost complete (96%) excretion of 1-OH-TMDD until 12 h after oral dosage. Elimination was bi-phasic, with half-lives of 0.75–1.6 h and 3.4–3.6 h for phases 1 and 2, respectively. The dermal application resulted in a delayed urinary excretion of this metabolite with a tmax of 12 h and complete excretion after about 48 h. The excreted amounts of 1-OH-TMDD represented 18% of the orally administered TMDD dose. The data of the metabolism study demonstrated a fast oral as well as substantial dermal resorption of TMDD. Moreover, the results indicated an effective metabolism of 1-OH-TMDD, which is excreted rapidly and completely via urine. Application of the method to 50 urine samples revealed a quantification rate of 90%, with an average concentration of 0.19 ng/mL (0.97 nmol/g creatinine). With the urinary excretion factor (Fue) derived from the metabolism study, we estimated an average daily intake of 1.65 µg TMDD from environmental and dietary sources. In conclusion, 1-OH-TMDD in urine is a suitable biomarker of exposure to TMDD and can be applied for biomonitoring of the general population. [ABSTRACT FROM AUTHOR]

Toxicokinetic modelling provides a powerful tool in relating internal human exposure (i.e., assessed through urinary biomarker levels) to external exposure. Chemical specific toxicokinetic models are available; however, this specificity prevents their application to similar contaminants or to other routes of exposure. For this reason, we investigated whether a generic physiological-based kinetic (PBK) model might be a suitable alternative for a biokinetic model of deoxynivalenol (DON). IndusChemFate (ICF) was selected as a generic PBK model, which could be fit for purpose. Being suited for simulating multiple routes of exposure, ICF has particularly been used to relate the inhalation and dermal exposure of industrial chemicals to their urinary excretion. For the first time, the ICF model was adapted as a generic model for the human biomonitoring of mycotoxins, thereby extending its applicability domain. For this purpose, chemical-specific data for DON and its metabolites were collected directly from the literature (distribution and metabolism) or indirectly (absorption and excretion) by fitting the ICF model to previously described urinary excretion data. The obtained results indicate that this generic model can be used to model the urinary excretion of DON and its glucuronidated metabolites following dietary exposure to DON. Additionally, the present study establishes the basis for further development of the model to include an inhalation exposure route alongside the oral exposure route. [ABSTRACT FROM AUTHOR]

An analytical strategy was applied to investigate polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like polychlorinated biphenyls (dl-PCBs) in newborn meconium samples. The methodology includes extraction by selective pressurized liquid extraction (SPLE), followed by a clean-up multicolumn step. The samples were injected by gas chromatography coupled to a high-resolution mass spectrometer (GC-HRMS). The surrogate recoveries ranged from 68% to 95%, and the average of the limit of quantification (LOQ) ranged from 0.03 to 0.08 pg g−1 wet weight (ww) for PCDD/Fs and 0.2 to 0.88 pg g−1 ww for dl-PCBs. The strategy was applied to 10 samples collected in Valencia (Spain) in 2022. In total, 18 out of 29 analysed congeners were detected in at least one sample, whereas 6 of them were detected in all the samples (OCDD, PCB-123, PCB-118, PCB-105, PCB-167, and PCB-156). The levels for the sum of the 17 congeners of PCDD/Fs and 12 congeners of dl-PCBs in the upper-bound (UB), expressed as picograms of toxic equivalency quantity (TEQ) per gram of ww, ranged from 0.19 to 0.31 pg TEQ g−1 ww. [ABSTRACT FROM AUTHOR]

There is limited and inconsistent evidence, primarily from cross-sectional studies, linking mycotoxins to adverse birth outcomes. This study investigates the potential role of maternal dietary exposure to multiple mycotoxins in the development of several adverse pregnancy and birth outcomes. We analyzed data from 436 singleton pregnancies enrolled in a prospective cohort study in the rural Habiganj district, Bangladesh, between July 2018 and November 2019. Thirty-five urinary mycotoxin biomarkers were quantified using liquid chromatography coupled with tandem mass spectrometry and used to estimate dietary mycotoxin exposure. Multivariable regression models, adjusted for potential confounding and clustering, were fitted to assess the associations between maternal exposure to frequently occurring mycotoxins (ochratoxin A-OTA, citrinin- CIT, and Deoxynivalenol- DON) and pregnancy loss, preterm birth (PTB), low birth weight (LBW), born small-for-gestational-age (SGA) and small-vulnerable newborn. The results indicate that only in 16 of 436 pregnancies (4%) were urine samples free from all investigated mycotoxins. Biomarkers for six major mycotoxins were detected in the urine samples. OTA (95%), CIT (61%), and DON (6%) were most frequently detected, with at least two mycotoxins co-occurring in the majority of women (63%). There was evidence that maternal dietary intake of OTA was associated with higher odds of having an LBW baby, with the odds increasing in a dose-dependent manner. We found no evidence of associations between pregnancy loss, PTB, SGA, small-vulnerable newborns, and maternal dietary exposure to OTA, CIT, and DON, albeit with large confidence intervals, so findings are consistent with protective as well as large harmful effects. Exposure to multiple mycotoxins during pregnancy is widespread in this rural community and represents a health risk for mothers and babies. Tailored public health policies and interventions must be implemented to reduce mycotoxin exposure to the lowest possible level. [ABSTRACT FROM AUTHOR]

The solvent 1,3-dichlorobenzene (1,3-DCB) is formed during thermal decomposition of the initiator 2,4-dichlorobenzoylperoxide in the production of silicone rubber with potential exposure of production workers as shown in previous works. Despite a threshold limit value (MAK value) of 2 ppm in air, there are currently no data about the corresponding internal exposure that would allow for the derivation of a biological limit value. In the present study, we have investigated the absorption of 1,3-DCB and urinary kinetics of its metabolites in 10 human volunteers after controlled inhalative exposure. Due to the strong odour of 1,3-DCB, a subjective evaluation of odour nuisance was also performed. Ten male human volunteers (23–36 yrs.) were exposed 6 h/day to a concentration of 0.7 ppm and 1.5 ppm in the Aachen workplace simulation laboratory (AWSL) with one week between each experiment. In order to investigate potential dermal absorption, the volunteers were exposed to 1.5 ppm wearing a suitable filter mask that prevented inhalative exposure in a third exposure. 1,3-DCB in blood was measured after 3 and 6 h exposure and the urinary metabolites 3,5-dichlorocatechol (3,5-DCC), 2,4-dichlorophenol (2,4-DCP) and 3,5-dichlorophenol (3,5-DCP) were measured over 24 h after exposure via LC/MS/MS. There were clear dose–response relations for all investigated parameters. The maximum excretion of the metabolites was reached at the end of exposure and corresponded to 5.2 ± 0.7 mg/g crea, 1.5 ± 0.35 mg/g crea and 0.07 ± 0.011 mg/g crea at 0.7 ppm and to 12.0 ± 3 mg/g crea, 3.5 ± 1.1 mg/g crea and 0.17 ± 0.05 mg/g crea at 1.5 ppm for 3,5-DCC, 2,4-DCP and 3,5-DCP, respectively. The use of filter masks decreased the internal exposure for about 85–90%, indicating substantial dermal absorption. Odour perception did not show a dose–response, probably due to fast olfactory adaption. The human study presented here provides an excellent basis for deriving a biological limit value for 1,3-DCB. [ABSTRACT FROM AUTHOR]

This review examined the mutagenicity and genotoxicity associated with exposure to outdoor air pollutants in Brazil. A search was performed on the Web of Science database using a combination of keywords that resulted in 134 articles. After applying exclusion criteria, a total of 75 articles were obtained. The articles were classified into three categories: (1) studies with plants and animals, (2) in vitro studies, and (3) human biomonitoring. The investigations were conducted in 11 of 27 Brazilian states with the highest prevalence in the southeast and south regions. Only 5 investigations focused on the effects of burning biomass on the quality of outdoor air. Plants, especially Tradescantia pallida, were the main air pollution biomonitoring tool. When available, a significant association between levels of air pollutants and genetic damage was described. Among the in vitro studies, Salmonella/microsome is the most used test to evaluate mutagenesis of outdoor air in Brazil (n = 26). Human biomonitoring studies were the least frequent category (n = 18). Most of the investigations utilized micronucleus bioassay, in oral mucosa cells (n = 15) and lymphocytes (n = 5), and the comet assay (n = 6). The analysis in this study points to the existence of gaps in genotoxicity studies and our findings indicate that future studies need to address the variety of potential sources of pollution existing in Brazil. In addition to extent of the impacts, consideration should be given to the enormous Brazilian biodiversity, as well as the determination of the role of socioeconomic inequality of the population in the observed outcomes. [ABSTRACT FROM AUTHOR]

Occupational exposure as a firefighter has recently been classified as a carcinogen to humans by International Agency for Research on Cancer (IARC). Biomonitoring has been increasingly used to characterize exposure of firefighting forces to contaminants. However, available data are dispersed and information on the most relevant and promising biomarkers in this context of firefighting is missing. This review presents a comprehensive summary and critical appraisal of existing biomarkers of exposure including volatile organic compounds such as polycyclic aromatic hydrocarbons, several other persistent other organic pollutants as well as heavy metals and metalloids detected in biological fluids of firefighters attending different fire scenarios. Urine was the most characterized matrix, followed by blood. Firefighters exhaled breath and saliva were poorly evaluated. Overall, biological levels of compounds were predominantly increased in firefighters after participation in firefighting activities. Biomonitoring studies combining different biomarkers of exposure and of effect are currently limited but exploratory findings are of high interest. However, biomonitoring still has some unresolved major limitations since reference or recommended values are not yet established for most biomarkers. In addition, half-lives values for most of the biomarkers have thus far not been defined, which significantly hampers the design of studies. These limitations need to be tackled urgently to improve risk assessment and support implementation of better more effective preventive strategies. [ABSTRACT FROM AUTHOR]

Tetrabromobisphenol A (TBBPA) is a known endocrine disruptor employed in a range of consumer products and has been predominantly found in different environments through industrial processes and in human samples. In this review, we aimed to summarize published scientific evidence on human biomonitoring, toxic effects and mode of action of TBBPA in humans. Interestingly, an overview of various pretreatment methods, emerging detection methods, and treatment methods was elucidated. Studies on exposure routes in humans, a combination of detection methods, adsorbent-based treatments and degradation of TBBPA are in the preliminary phase and have several limitations. Therefore, in-depth studies on these subjects should be considered to enhance the accurate body load of non-invasive matrix, external exposure levels, optimal design of combined detection techniques, and degrading technology of TBBPA. Overall, this review will improve the scientific comprehension of TBBPA in humans as well as the environment, and the breakthrough for treating waste products containing TBBPA. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the practicability of exhaled breath condensate (EBC) as a biological matrix to detect and measure hexavalent chromium (Cr(VI)) and trivalent chromium (Cr(III)) in workers occupationally exposed to Cr(VI). EBC samples were collected from workers in France, Finland, Italy, The Netherlands and the United Kingdom from three different target activities: chrome platers, stainless steel welders and surface treatment workers. Pre and post working week EBC samples were collected from 177 exposed workers and 98 unexposed workers (control group). Hyphenated chromatography systems with inductively coupled plasma – mass spectrometry (ICP-MS) were for the analysis. The results showed that the occupationally exposed workers had significantly higher levels of Cr(VI) and Cr(III) than the control group. Chrome platers exhibited the highest Cr(VI) levels in their EBC samples, with a significant increase from their pre to post samples for both Cr(VI) and Cr(III). A significant difference was also found between pre and post EBC samples for Cr(III) in welders. This study has shown that EBC has the potential to be a valid, non-invasive biological matrix to assess occupational exposure to Cr(VI) and Cr(III) for biological monitoring assessment, with the ability to detect low level inhalation exposures. [Display omitted] • Exhaled breath condensate (EBC) reflects tri- and hexavalent chromium in the lungs. • Both chromium species were higher in EBC of workers compared to controls. • Both chromium species increased from pre to post workweek EBC in chrome platers. • EBC may provide lung-specific, non-invasive occupational exposure data for hexavalent chromium. [ABSTRACT FROM AUTHOR]

Technical grade branched nonylphenol (NP) was determined in human urine by online solid phase extraction–ultra high-performance liquid chromatography–tandem mass spectrometry (SPE–UHPLC–MS/MS). Prior to analysis, urine specimens were simply diluted and enzymatically deconjugated. The run time of the chromatography, including SPE and re-equilibration, was 9 min per injection. The enzymatic cleavage of NP conjugates was optimised with incurred sample material from a human metabolism study: the highest recoveries were obtained with β-glucuronidase from E. coli K 12 in 0.1 M ammonium acetate at pH 6.5, within a minimal hydrolysis time of 30 to 60 min. Using sodium acetate instead of ammonium acetate led to systematically decreased recovery rates. The analytical method was validated regarding its precision (coefficients of variation: 2.9–7.4%), accuracy (relative recovery rates: 93–105%), robustness (relative recovery rates in individual urine matrices: 92–117%), selectivity, and limit of quantification (1.0 μg L−1). Fundamental aspects in the analysis of technical product mixtures such as NP, comprising various isomers and homologues, were considered. Validation results, an exposure scenario and the application of the procedure to real samples, show that it enables a rugged monitoring of NP exposures above, at, and significantly below health-based guidance values, corresponding to daily NP intakes in the low μg kg−1 d−1 range. On the other hand, background levels in non-specifically exposed populations cannot be detected with this method. Hence, while alternative approaches should be pursued for NP analysis at environmental trace level, the speed and simplicity of our method are ideal for high-throughput human biomonitoring in occupational medicine. [ABSTRACT FROM AUTHOR]

Many xenobiotics were identified as possible endocrine disruptors during the last decades. Structural analogy of these substances to natural hormones may lead to agonists or antagonists of hormone receptors. For a comprehensive human biomonitoring of such substances, we developed a simple, reliable, and highly sensitive method for the simultaneous monitoring of the parameters bisphenol A, triclosan, methylparaben, ethylparaben, propylparaben, butylparaben, benzophenone-1, benzophenone-3, 3,5,6-trichloropyridin-2-ol, p-nitrophenol, genistein, and daidzein in urine. Thereby, optimization of the enzymatic hydrolysis and the use of β-glucuronidase from E. coli K12 as well as sulfatase from Aerobacter aerogenes ensures the acquisition of intact analytes without cleavage of ester bonds among parabens. Validation of the method revealed limits of detection between 0.02 and 0.25 µg/L as well as limits of quantification between 0.08 and 0.83 µg/L. Thereby, the use of analyte-free surrogate matrix for calibration and control material influenced the sensitivity of the procedure positively. Furthermore, excellent precision in and between series was observed. Good absolute and relative recoveries additionally proved the robustness of the multimethod. Thus, the procedure can be applied for exploring the exposome to these prominent endocrine disruptors in the general population. [ABSTRACT FROM AUTHOR]

The article summarises the results of Czech Human Biomonitoring over a period of three decades. Human biomonitoring in the Czech Republic was commenced at the National Institute of Public Health, Prague, in 1994 as part of the Environmental Health Monitoring System and was later linked to European and worldwide professional activities in this area. During the course of this project the whole range of organic and inorganic xenobiotics and essential substances was monitored in the blood, urine and hair of the adult and child populations, in the breast milk of breastfeeding women and in other, less common matrices. The results have provided valuable long-term time series that show how established preventive measures can work in practice and how they correspond to decreasing population exposure. Results can also be used to verify whether or not, and how quickly, can individuals be exposed to newly used chemical substances. Results of human biological monitoring are important for public health professionals to establish reference values, to provide comparison with health limits, to assess health risks, for health policy purposes and international comparison. Appropriately processed results can serve to inform and educate the public about human population burden by chemical substances in the environment. Long-term experience in the field of human biomonitoring enables experts of the National Institute of Public Health to participate in many foreign projects focused on monitoring the exposure of various population groups to chemical substances from the environment. [ABSTRACT FROM AUTHOR]

UV-327 (2-(5-chloro-benzotriazol-2-yl)-4,6-di-(tert-butyl)phenol) is used as an ultraviolet (UV) absorber in plastic products and coatings. Due to its ubiquitous distribution in the environment, human exposure is conceivable. In the study presented herein, initial information on the human in vivo metabolism of UV-327 was obtained by single oral administration to three volunteers. Urine and blood samples were collected up to 72 h after exposure. One study participant additionally donated plasma samples. Maximum blood and plasma levels of UV-327 and its two monohydroxylated metabolites UV-327-6-mOH and UV-327-4-mOH were reached 6 h post-exposure. Almost the entire amount found in blood and plasma samples was identified as UV-327, whereas the two metabolites each accounted for only 0.04% of the total amount, indicating that UV-327 is well-absorbed from the intestine, but only partially metabolized. Plasma to blood ratios of UV-327, UV-327-6-mOH, and UV-327-4-mOH ranged from 1.5 to 1.6. Maximum urinary excretion rates of UV-327, UV-327-6-mOH, UV-327-4-mOH, and UV-327-4 + 6-diOH were reached 9–14 h post-exposure. However, only about 0.03% of the orally administered dose of UV-327 was recovered as UV-327 and its metabolites in urine, indicating that biliary excretion may be the major route of elimination of UV-327 and its hydroxylated metabolites. The present study complements the insight in the complex absorption, distribution, metabolism, and elimination (ADME) processes of benzotriazole UV stabilizers (BUVSs). [ABSTRACT FROM AUTHOR]

Early human life is considered a critical window of susceptibility to external exposures. Infants are exposed to a multitude of environmental factors, collectively referred to as the exposome. The chemical exposome can be summarized as the sum of all xenobiotics that humans are exposed to throughout a lifetime. We review different exposure classes and routes that impact fetal and infant metabolism and the potential toxicological role of mixture effects. We also discuss the progress in human biomonitoring and present possiblemodels for studying maternal–fetal transfer. Data gaps on prenatal and infant exposure to xenobiotic mixtures are identified and include natural biotoxins, in addition to commonly reported synthetic toxicants, to obtain a more holistic assessment of the chemical exposome. We highlight the lack of large-scale studies covering a broad range of xenobiotics. Several recommendations to advance our understanding of the early-life chemical exposome and the subsequent impact on health outcomes are proposed. [ABSTRACT FROM AUTHOR]

An overview of recent European background inorganic arsenic (iAs) levels and related human health risks is given. The main aim was to summarize and confront the existing concentration data, unresolved low dose-response issues (linearity, nonlinearity, threshold, adaptation, hormesis), and methodological approaches hampered by several uncertainties on several levels. Daily doses are calculated from dietary intake (food, water As content multiplied by intake frequencies) and compared by reverse calculated doses from urine iAs metabolites (iAs + dimethylarsenic acid + monomethylarsonic acid) from human biomonitoring data (both in a range 0.05–0.60 μg kg−1 bw/day for children, adolescents and adults). With data obtained a health risk assessment is performed by existing regulation norms. Several flaws are addressed. For instance, urine DMA used as iAs metabolite is overestimated as its source can also be food items. Further, existing regulation norms (which are under reevaluation by US EPA) are based on a linear dose-response approach valid for high exposure only and highly questionable at low exposure levels. Nevertheless, even by using the conventional approaches with discussed flaws leading to anticipated overestimation, the potential cancer risk was estimated to be of low concern regarding the margins of exposure (MOE) for investigated age groups with average food intake and average iAs concentration in diet (15.3–40.6), supported by MOE calculated from human biomonitoring data (21.4). [ABSTRACT FROM AUTHOR]

Phthalates and bisphenol A (BPA) are plasticizers used in many industrial products that can act as endocrine disruptors and lead to metabolic diseases. During the LIFE PERSUADED project, we measured the urinary concentrations of BPA and Di(2-ethylhexyl)phthalate (DEHP) metabolites in 900 Italian women representative of the Italian female adult population (living in the north, centre, and south of Italy in both rural and urban areas). The whole cohort was exposed to DEHP and BPA with measurable levels above limit of detection in more than 99% and 95% of the samples, respectively. The exposure patterns differed for the two chemicals in the three macro-areas with the highest urinary levels for DEHP in south compared to central and northern Italy and for BPA in northern compared to central and southern Italy. BPA levels were higher in women living in urban areas, whereas no difference between areas was observed for DEHP. The estimated daily intake of BPA was 0.11 μg/kg per day, about 36-fold below the current temporary tolerable daily intake of 4 μg/kg per day established by the EFSA in 2015. The analysis of cumulative exposure showed a positive correlation between DEHP and BPA. Further, the reduction of exposure to DEHP and BPA, through specific legislative measures, is necessary to limit the harmfulness of these substances. [ABSTRACT FROM AUTHOR]

Mycotoxins are natural metabolites produced by fungi that contaminate food and feed worldwide. They can pose a threat to human and animal health, mainly causing chronic effects, e.g., immunotoxic and carcinogenic. Due to climate change, an increase in European population exposure to mycotoxins is expected to occur, raising public health concerns. This urges us to assess the current human exposure to mycotoxins in Europe to allow monitoring exposure and prevent future health impacts. The mycotoxins deoxynivalenol (DON) and fumonisin B1 (FB1) were considered as priority substances to be studied within the European Human Biomonitoring Initiative (HBM4EU) to generate knowledge on internal exposure and their potential health impacts. Several policy questions were addressed concerning hazard characterization, exposure and risk assessment. The present article presents the current advances attained under the HBM4EU, research needs and gaps. Overall, the knowledge on the European population risk from exposure to DON was improved by using new harmonised data and a newly derived reference value. In addition, mechanistic information on FB1 was, for the first time, organized into an adverse outcome pathway for a congenital anomaly. It is expected that this knowledge will support policy making and contribute to driving new Human Biomonitoring (HBM) studies on mycotoxin exposure in Europe. [ABSTRACT FROM AUTHOR]

Human biomonitoring of toxic and essential trace elements is critically important for public health protection. Amazonian riverine communities exhibit distinctive dietary patterns, heavily reliant on locally sourced fish, fruits, and vegetables. These habits may result in unique exposure profiles compared to urban populations. However, comprehensive assessments of their exposure to toxic and essential metals are lacking, representing a critical gap in understanding the health risks faced by these communities. This study aimed to establish baseline levels of 21 metals and metalloids in human blood and explore the influence of sociodemographic factors, dietary habits, and lifestyle choices as potential sources of exposure to these elements. A cross-sectional biomonitoring investigation was conducted with 1,024 individuals from 13 communities in the Tapajós and Amazon Basins (Pará, Brazil). Most of the elements in study was determined for the first time in the region. Blood samples were analyzed using inductively coupled plasma mass spectrometry (ICP-MS). The levels of all elements were summarized by quantiles and compared with cutoff values from other Brazilian populations. Multiple linear regression was used to assess possible associations between element concentrations and sociodemographic characteristics, dietary habits, and lifestyle choices. High detection rates (64%–100%) were observed, indicating the widespread presence of these elements. Elevated blood concentrations were found for mercury (median 21.1 μg.L−1, interquartile range: 12–34 μg.L−1), selenium (median 166 μg.L−1, interquartile range: 137–208 μg.L−1), and lead (median 34 μg.L−1, interquartile range: 20.8–64 μg.L−1). Regression analysis revealed a positive association between mercury levels and fish consumption, while manioc flour intake showed no relationship to lead levels. In conclusion, our findings emphasize the need for continued monitoring and public policy development for these vulnerable populations. Further studies should assess long-term trends and investigate the health implications of prolonged exposure to diverse chemicals in Amazonian riverside communities. • We established reference ranges for 21 metals and metalloids in the blood of the Amazon riverside population. • We recruited 1,024 individuals from 13 communities in the Tapajós and Amazon river basins. • Elevated blood concentrations of mercury, selenium, and lead were detected. • Potential sources of exposure were identified through multiple linear regression analysis. • Future studies will evaluate long-term trends and health impacts of prolonged exposure to these elements. [ABSTRACT FROM AUTHOR]

Long-term biomonitoring of urinary metal ions is an essential tool for the epidemiological assessment of chronic exposure levels, enabling us to track changes in metal exposure over time and better understand its health implications. In this study, we evaluated the temporal trends of urinary metal ions among 1962 residents of Guangzhou, China, from 2018 to 2022. The total metal ion concentrations in the urine of the population did not change significantly between 2018 and 2019. With the onset of the COVID-19 pandemic in 2020, urinary total metal ion concentrations began to decline dramatically, reaching their lowest level in 2021. A rebound in concentrations was observed in 2022, which returned to the initial levels observed in 2018. Urine chromium and cadmium concentrations peaked in 2020, while urinary lead levels were the highest in 2021, and urinary nickel concentrations were the highest in 2022. Males consistently displayed higher urinary concentrations of lead and arsenic throughout each year of the study. Furthermore, minors consistently had higher urinary nickel levels than adults, whereas adults consistently had higher urinary cadmium concentrations than minors. Cluster analyses were conducted annually on urinary metal ions to examine the differences in their distribution and to evaluate changes in metal exposure patterns over time. The Monte Carlo simulations indicate that the whole population exhibits a high non-carcinogenic risk from arsenic exposure and significant carcinogenic risks associated with exposure to nickel, arsenic, chromium, and cadmium. The next two years were predicted by a gray prediction model, and the results are tested using mean absolute percentage error which demonstrating high accuracy. [Display omitted] • Biomonitoring shows urinary metal concentrations changes from 2018 to 2022. • Significant carcinogenic risks from Ni, Cd, and As for the whole population. • Adolescents show elevated urinary nickel, adults exhibited higher cadmium levels. • Cluster analyses uncover changing patterns of urinary metal ion distribution. • Urinary metal concentrations for the next two years were predicted accurately. [ABSTRACT FROM AUTHOR]

• An easy method for polyclyclic aromatic hydrocarbons (PAHs) quantitation in human saliva is presented. • PDMS/DVB/PDMS fiber was used in direct immersion for extraction of thirteen PAHs including low-volatile analytes such as benzo[a]pyrene and dibenzo[a,h]anthracene. • The evaluation of the robustness of fiber coating over time revealed highly satisfactory extraction performance, with no significant drop in signal. • The target compounds were quantified with LLOQs at 100 and 500 ng/L. • The "green" character of the procedure was evaluated by greenness metrics. This work presents a novel method for the analysis of polycyclic aromatic hydrocarbons (PAHs) in saliva samples using solid phase microextraction (SPME) coupled with gas chromatography-triple quadrupole mass spectrometry (GC-QqQ-MS). The protocol utilizes the latest commercially available overcoated fiber (PDMS/DVB/PDMS) for direct immersion extraction of the target analytes, enabling the determination of thirteen PAHs, including low-volatile compounds. The SPME extraction method was optimized using a central composite design (CCD). The evaluation of the fiber coating's robustness over time demonstrated excellent extraction performance with no significant degradation. The validation procedure confirmed good performance for all parameters, with LOQ values (100 ng/L for ten analytes and 500 ng/L for three analytes) comparable to other chromatographic methods. The environmental impact of the protocol was objectively assessed using two recently proposed metrics: the Green Analytical Procedure Index (GAPI) and the Analytical Greenness metric for sample preparation (AGREEprep). Both metrics indicated good overall environmental friendliness, with AGREEprep providing a satisfactory comprehensive score despite the use of highly impactful instrumentation. These characteristics make the developed method suitable for routine analysis in environmental and epidemiological monitoring. [ABSTRACT FROM AUTHOR]

Continuous human biomonitoring and predictive modelling of urinary pesticide metabolites are critical for evaluating pesticide exposure trends and associated health risks. We conducted repeat cross-sectional surveys to determine the urinary concentrations of eight pesticide metabolites in the residents of Guangzhou, China, from 2018 to 2022. We longitudinally analyzed the changes in these metabolite concentrations over the years and assessed the potential non-carcinogenic risks by calculating the hazard quotient and hazard index. No significant differences were observed in the total urinary pesticide metabolite concentrations over the 5 years (9.16–12.99 μg/L). The urinary concentrations of 3,5,6-trichloro-2-pyridinol and 2,4-dichlorophenoxyacetic acid reached their lowest levels in 2020 (1.47 and 0.11 μg/L). Conversely, urinary para -nitrophenol concentrations exhibited an inverse trend, peaking in 2020 (6.16 μg/L). The composition profiles of urinary pesticide metabolites showed that para -nitrophenol consistently constituted the largest proportion each year. Males consistently showed higher median concentrations of total urinary pesticide metabolites and individual metabolites of 3,5,6-trichloro-2-pyridinol, trans -3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid, and para -nitrophenol than females. The concentrations of cis -3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid in adults' urine were significantly higher than those in minors' urine each year. The total pesticide metabolite concentrations in adults' urine were significantly higher than those in minors' urine in 2018 and 2020, whereas no significant differences were observed in other years. No significant differences in urinary pesticide metabolite concentrations were observed among different BMI groups. Results showed that 14.17% of the population had hazard index values above 1, indicating a higher risk of health hazards. Three predictive models were employed to predict urinary pesticide metabolite concentrations for 2023–2024, revealing an increasing trend in 3,5,6-trichloro-2-pyridinol concentrations while other metabolites are expected to decrease. The study showed the concentration of para -nitrophenol peaked in 2020 while 3,5,6-trichloro-2-pyridinol and 2,4-dichlorophenoxyacetic acid reached their lowest levels, suggests that the COVID-19 pandemic may have influenced pesticide exposure patterns. [Display omitted] • Total urinary pesticide metabolites showed a decreasing trend from 2018 to 2022. • Males had consistently higher pesticide metabolite concentrations than females. • 14.17% of the population had hazard index value higher than 1. • Predictive models suggest increasing TCPY, decreasing trends for other metabolites. • COVID-19 pandemic may have influenced pesticide exposure patterns. [ABSTRACT FROM AUTHOR]

[Display omitted] • Urine samples from 587 women in the 34th week of pregnancy were analyzed by LC-HRMS. • Pesticide residues and polyphenols were annotated in the same data set. • 40 pesticide residues associated with exposure to 27 pesticides were reported. • 46 polyphenols were identified and used for a cluster analysis. • Citrus fruit consumption might associate with pyrimethanil metabolites. Human exposure to pesticides in the general population occurs mainly through food consumption. However, specific dietary habits or food products that contribute to pesticide exposure are often unknown. In this study, we propose a combined screening for polyphenols and pesticide residues by liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) to assess the diet and the associated pesticide exposure. We measured 587 urine samples from women around the 34th week of pregnancy of a prospective mother–child cohort. A non-targeted screening for flavonoid-like compounds related to fruit and vegetable consumption was performed, prioritizing 164 features and identifying a total of 46 features by spectral library search. Based on a subset of markers, k-means clustering was performed, leading to four clusters with presumably similar dietary habits. The clusters were compared against food questionnaire data collected within the period of sample collection. Suspect screening of more than 500 pesticide residues including metabolites was performed, with a total of 40 residues being reported for 27 different pesticides. The detection of pesticide residues was compared across the different clusters of dietary habits. Indications were found that pyrimethanil metabolites might be associated with the consumption of citrus fruits or derivate products. We demonstrate that the method used has the potential to reveal patterns of pesticide intake from specific food commodities. [ABSTRACT FROM AUTHOR]

Historically, benzene has been widely used in a large variety of applications. Occupational exposure limits (OELs) were set for benzene as it was found to be acutely toxic, causing central nervous system depression at high exposures. OELs were lowered when it was discovered that chronic exposure to benzene could cause haematotoxicity. After confirmation that benzene is a human carcinogen causing acute myeloid leukaemia and possibly other blood malignancies, OEL were further lowered. The industrial application of benzene as solvent is almost completely discontinued but it is still used as feedstock for the production of other materials, such as styrene. Occupational exposure to benzene may also occur since it is present in crude oil, natural gas condensate and a variety of petroleum products and because benzene can be formed in combustion of organic material. In the past few years, lower OELs for benzene in the range of 0.05–0.25 ppm have been proposed or were already established to protect workers from benzene-induced cancer. The skin is an important potential route of exposure and relatively more important at lower OELs. Consequently, human biomonitoring – which integrates all exposure routes – is routinely applied to control overall exposure to benzene. Several potential biomarkers have been proposed and investigated. For compliance check of the current low OELs, urinary S-phenylmercapturic acid (S-PMA), urinary benzene and blood benzene are feasible biomarkers. S-PMA appears to be the most promising biomarker but proper validation of biomarker levels corresponding to airborne benzene concentrations below 0.25 ppm are needed. [ABSTRACT FROM AUTHOR]

Infants are sensitive to negative effects caused by food contaminants such as mycotoxins. To date, analytical methods assessing mycotoxin mixture exposure in infant stool are absent. Herein, we present a novel multi-mycotoxin LC-MS/MS assay capable of detecting 30+ analytes including the regulated mycotoxin classes (aflatoxins, trichothecenes, ochratoxins, zearalenone, citrinin), emerging Alternaria and Fusarium toxins, and several key metabolites. Sample preparation consisted of a 'dilute, filter, and shoot' approach. The method was in-house validated and demonstrated that 25 analytes fulfilled all required criteria despite the high diversity of chemical structures included. Extraction recoveries for most of the analytes were in the range of 65–114% with standard deviations below 30% and limits of detection between 0.03 and 11.3 ng/g dry weight. To prove the methods' applicability, 22 human stool samples from premature Austrian infants (n = 12) and 12-month-old Nigerian infants (n = 10) were analyzed. The majority of the Nigerian samples were contaminated with alternariol monomethyl ether (8/10) and fumonisin B1 (8/10), while fumonisin B2 and citrinin were quantified in some samples. No mycotoxins were detected in any of the Austrian samples. The method can be used for sensitive human biomonitoring (HBM) purposes and to support exposure and, potentially, risk assessment of mycotoxins. Moreover, it allows for investigating potential associations between toxicant exposure and the infants' developing gut microbiome. [ABSTRACT FROM AUTHOR]

Aflatoxins (AFs), ochratoxin A (OTA), citrinin (CIT), fumonisin B1 (FB1), zearalenone (ZEN), and deoxynivalenol (DON) are mycotoxins that may contaminate diets, especially in low-income settings, with potentially severe health consequences. This study investigates the exposure of 439 pregnant women in rural Bangladesh to 35 mycotoxins and their corresponding health risks and links their exposure to certain foods and local stimulants. Overall, 447 first-morning urine samples were collected from pregnant women between July 2018 and November 2019. Mycotoxin biomarkers were quantified by DaS-HPLC–MS/MS. Urinary concentration of frequently occurring mycotoxins was used to estimate dietary mycotoxin exposure. Median regression analyses were performed to investigate the association between the consumption of certain foods and local stimulants, and urinary concentration of frequently occurring mycotoxins. Only in 17 of 447 urine samples (4%) were none of the investigated mycotoxins detected. Biomarkers for six major mycotoxins (AFs, CIT, DON, FB1, OTA, and ZEN) were detected in the urine samples. OTA (95%), CIT (61%), and DON (6%) were most frequently detected, with multiple mycotoxins co-occurring in 281/447 (63%) of urine samples. Under the lowest exposure scenario, dietary exposure to OTA, CIT, and DON was of public health concern in 95%, 16%, and 1% of the pregnant women, respectively. Consumption of specific foods and local stimulants—betel nut, betel leaf, and chewing tobacco—were associated with OTA, CIT, and DON urine levels. In conclusion, exposure to multiple mycotoxins during early pregnancy is widespread in this rural community and represents a potential health risk for mothers and their offspring. [ABSTRACT FROM AUTHOR]

A human biomonitoring study was conducted to assess the exposure of Hungarian children aged 8–11 years to ten phthalate esters (PEs) and DINCH between 2017 and 2018. In addition to collecting urine samples from 262 participants, a questionnaire was completed by the parents or legal guardians to identify potential determinants of exposure. The highest geometric mean concentration was observed for MiBP, followed by MBP, cx- MEHP, OH-MEHP and MEP. Three out of the four DINCH metabolites were detected in more than 90% of the samples. The comparison of the urinary concentrations measured in this study with those observed in the DEMOCOPHES study revealed a significant decreasing trend in all PE metabolites investigated in both studies between 2011/2012 and 2017/2018. Different approaches were used to assess the health risks associated with the exposure to PEs and DINCH. Our results highlighted that the hazard index (HI) values were higher than 1 in 17.6% of the children when the human biomonitoring guidance values were applied. In contrast, less than 3% of the children had HI values exceeding 1 when other sources of reference values were used. By applying a safety factor of 10 for the risk assessment, 17.6–91.6% of the children were characterized by HI values higher than 0.1, indicating the need for risk reduction measures. Overall, DnBP, DiBP and DEHP were identified as the main drivers of the mixture risk. Although PEs and DINCH are ubiquitous contaminants, there are still inconsistencies and gaps in our understanding of the determinants of exposure. The results of the multivariate regression analysis showed significant associations between PE or DINCH metabolite concentrations and certain individual characteristics, use of personal care products, home and school environment and food and beverages consumption 24 h prior to sample collection. • Almost all children were exposed to DEP, DiBP, DnBP, BBzP, DEHP, DiNP, DiDP, DINCH. • Exposure to phthalates significantly decreased between 2011/2012 and 2017/2018. • Overall, DnBP, DiBP and DEHP were identified as the main drivers of the mixture risk. • The results of the risk assessment justify the need for risk reduction measures. • Several exposure determinants have been identified in this study. [ABSTRACT FROM AUTHOR]

Perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), and perfluorononanoic acid (PFNA) are persistent contaminants detected in human blood worldwide, raising significant health concerns. In response, countries such as the United States and Australia have implemented regulatory measures to limit their use. This study analysed temporal trends in serum concentrations of these four PFAS and how these trends align with regulatory measures, using data from NHANES (2003–2004 to 2017–2018) and the Australian Human Biomonitoring Program (2002–2003 to 2020–2021). Multiple regression analyses adjusted for age and gender were performed to estimate mean concentration changes over time, and differences within each dataset were assessed. Results indicated significant reductions (p < 0.001) in PFOS, PFOA, and PFHxS concentrations post-2002-2003, while PFNA concentrations increased until 2009–2010 before declining in both Australia and the U.S. Age-related trends in the U.S. during the last monitoring period showed higher PFAS concentrations in the oldest age groups, while in Australia, this trend was evident for PFOS and PFHxS. In Australia, the age group of 0–5 years had PFOA and PFNA concentrations similar to those of adults over 46 years, indicating ongoing exposure. Gender differences were consistent in both programs, with females aged 6–15, 31–45, and 46–60 years exhibiting lower serum concentrations, particularly in the 31–45 years age group. These findings support Australian and U.S. efforts to reduce PFAS exposure through regulatory actions, highlight the need to address ongoing exposure in young children, and consider gender-specific factors affecting PFAS concentrations. • PFOS, PFOA, and PFHxS concentrations decreased significantly after 2002–2003. • PFNA concentrations rose until 2010, followed by a subsequent decline. • In Australia, PFOA and PFNA concentrations in children 0–5 years were similar to those in adults. • Females in the age group 31 to 45 have significantly lower concentrations than males. [ABSTRACT FROM AUTHOR]