Assessment of internal exposure risk from metals pollution of occupational and non-occupational populations around a non-ferrous metal smelting plant.

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.

A direct immersion-solid-phase microextraction method for the automated determination of 3- to 6-ring polycyclic aromatic hydrocarbons in saliva by gas-chromatography-tandem mass spectrometry.

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.

In Vitro Metabolism of Quaternary Ammonium Compounds and Confirmation in Human Urine by Liquid Chromatography Ion-Mobility High-Resolution Mass Spectrometry.

Quaternary ammonium compounds (QACs) are high-production chemicals used as cleaning and disinfecting agents. Due to their ubiquitous presence in the environment and several toxic effects described, human exposure to these chemicals gained increasing attention in recent years. However, very limited data on the biotransformation of QACs is available, hampering exposure assessment. In this study, three QACs (dimethyl dodecyl ammonium, C10-DDAC; benzyldimethyl dodecylammonium, C12-BAC; cetyltrimethylammonium, C16-ATMAC) commonly detected in indoor microenvironments were incubated with human liver microsomes and cytosol (HLM/HLC) simulating Phase I and II metabolism. Thirty-one Phase I metabolites were annotated originating from 19 biotransformation reactions. Four metabolites of C10-DDAC were described for the first time. A detailed assessment of experimental fragmentation spectra allowed to characterize potential oxidation sites. For each annotated metabolite, drift-tube ion-mobility derived collision cross section (DTCCSN2) values were reported, serving as an additional identification parameter and allowing the characterization of changes in DTCCSN2 values following metabolism. Lastly, eight metabolites, including four metabolites of both C12-BAC and C10-DDAC, were confirmed in human urine samples showing high oxidation states through introduction of up to four oxygen atoms. This is the first report of higher oxidized C10-DDAC metabolites in human urine facilitating future biomonitoring studies on QACs.

Kinetic Considerations in the Interpretation of Biomonitoring of 1,3-Butadiene Exposure by Determination of Urinary Mercapturic Acids.

1,3-Butadiene (BD) is classified as a human carcinogen, and occupational exposure should be minimized. This study examined the effectiveness of personal protective equipment (PPE) during the clean-up and repair of a storage tank containing sludge contaminated with BD. A total of 66 workers participated, providing repeat urine samples before and after the shift. Overall, 1286 samples were analyzed for 1,2-dihydroxy-4-(N-acetylcysteinyl)butane (DHBMA) and the isomers 2-hydroxy-1-(N-acetylcysteinyl)-3-butene and 1-hydroxy-2-(N-acetylcysteinyl)-3-butene (MHBMA). Both DHBMA and MHBMA are urinary metabolites of BD and serve as biomarkers for recent BD exposure. Established correlations between the urinary concentrations of these biomarkers and airborne BD levels allowed for exposure assessment. However, conclusions regarding the exceedances of occupational exposure limits can vary depending on whether DHBMA or MHBMA levels are considered. This study investigated this discrepancy by estimating the apparent urinary half-lives of DHBMA and MHBMA using sequential individual post- and pre-shift samples. The results indicated that the longer urinary half-life of MHBMA (19.7 ± 3.1 h) led to its accumulation during the work week, in contrast to DHBMA, which has a shorter half-life (10.3 ± 1.9 h) and showed limited accumulation. When the kinetic information was used to adjust for the MHBMA build-up over the week, the discrepancy with DHBMA resolved, confirming that exposure limit values were not exceeded and validating the effectiveness of the PPE used. In the context of biomonitoring, this study provides valuable insights into biomarker selection based on specific objectives. MHBMA is recommended for scenarios with uncertain exposure timing and activities, whereas DHBMA is the preferred biomarker for evaluating the effectiveness of protective measures in known exposure settings.

Longitudinal study and predictive modelling of urinary pesticide metabolite concentrations in residents of Guangzhou, China.

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.

Multiple mycotoxin exposure assessment through human biomonitoring in an esophageal cancer case-control study in the Arsi-Bale districts of Oromia region of Ethiopia.

BACKGROUND: Esophageal cancer (EC) is a malignancy with a poor prognosis and a five-year survival rate of less than 20%. It is the ninth most frequent cancer globally and the sixth leading cause of cancer-related deaths. The incidence of EC has been found to vary significantly by geography, indicating the importance of environmental and lifestyle factors along with genetic factors in the onset of the disease. In this work, we investigated mycotoxin exposure in a case-control study from the Arsi-Bale districts of Oromia regional state in Ethiopia, where there is a high incidence of EC while alcohol and tobacco use - two established risk factors for EC - are very rare. METHODS: Internal exposure to 39 mycotoxins and metabolites was assessed by liquid chromatography-tandem mass spectrometry in plasma samples of EC cases (n = 166) and location-matched healthy controls (n = 166) who shared similar dietary sources. Demographic and lifestyle data were collected using structured questionnaires. Principal Component Analysis and machine learning models were used to identify the most relevant demographic, lifestyle, and mycotoxin (co-)exposure variables associated with EC. Multivariate binary logistic regression analysis was used to assess EC risk. RESULT: Evidence of mycotoxin exposure was observed in all plasma samples, with 10 different mycotoxins being detected in samples from EC cases, while only 6 different mycotoxins were detected in samples from healthy controls. Ochratoxin A was detected in plasma from all cases and controls, while tenuazonic acid was detected in plasma of 145 (87.3%) cases and 71 (42.8%) controls. Using multivariable logistic regression analysis, exposure to tenuazonic acid (AOR = 1.88 [95% CI: 1.68-2.11]) and to multiple mycotoxins (AOR = 2.54 [95% CI: 2.10-3.07]) were positively associated with EC. CONCLUSION: All cases and controls were exposed to at least one mycotoxin. Cases were exposed to a statistically significantly higher number of mycotoxins than controls. Exposure to tenuazonic acid and to multiple mycotoxins were associated with increased risk of EC in the study population. Although aflatoxin B1-lysine and the ratio of sphinganine to sphingosine (as a biomarker of effect to fumonisin exposure) were not assessed in this study, our result emphasizes the need to characterize the effect of mycotoxin co-exposure as part of the exposome and include it in risk assessment, since the current mycotoxin safety levels do not consider the additive or synergistic effects of mycotoxin co-exposure. Moreover, a prospective study design with regular sampling should be considered in this high incidence area of EC in Ethiopia to obtain conclusive results on the role of mycotoxin exposure in the onset and development of the disease.

Effects of Environmental Tobacco Smoke on Oxidative Stress in Childhood: A Human Biomonitoring Study.

Household smoking is one of the main sources of environmental tobacco smoke (ETS) exposure for children, a population considered to be at high risk for associated negative health outcomes. Several studies evidenced the occurrence of early effects related to ETS exposure, including the development of the oxidative stress process. The aim of this study was to evaluate the correlation between urinary levels of 8-oxo-7,8-dihydro-2-deoxyguanosine (8oxodGuo), a nucleic acid oxidation biomarker, and socio-demographic features and lifestyle factors in school children (aged 5-11 years). A cross-sectional study was conducted among 154 healthy children, residing in rural zones of central Italy. For each participant, one urine sample was analyzed by the HPLC-MS/MS technique to simultaneously quantify 8oxodGuo and cotinine (a biomarker of ETS exposure), while information on the children was collected using a questionnaire filled out by the parents. Urinary levels of 8oxodGuo was found to be significantly higher in children exposed to ETS compared to those not exposed (5.53 vs. 4.78 µg/L; p = 0.019). This result was confirmed by the significant association observed between urinary levels of cotinine and 8oxodGuo (r = 0.364, p < 0.0001). Additionally, children exposed to ETS with no smoking ban at home showed a further increased difference than those not exposed (6.35 µg/L vs. 4.78 µg/L; p = 0.008). Considering the great number of adverse effects on human health due to exposure to passive smoking, especially if this exposure begins early in life, it is essential to implement health promotion interventions in this area.

Phthalate and DINCH metabolites in the urine of Hungarian schoolchildren: Cumulative risk assessment and exposure determinants.

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.

Exposure to bisphenol A in European women from 2007 to 2014 using human biomonitoring data - The European Joint Programme HBM4EU.

BACKGROUND: Bisphenol A (BPA; or 4,4'-isopropylidenediphenol) is an endocrine disrupting chemical. It was widely used in a variety of plastic-based manufactured products for several years. The European Food Safety Authority (EFSA) recently reduced the Tolerable Daily Intake (TDI) for BPA by 20,000 times due to concerns about immune-toxicity. OBJECTIVE: We used human biomonitoring (HBM) data to investigate the general level of BPA exposure from 2007 to 2014 of European women aged 18-73 years (n = 4,226) and its determinants. METHODS: Fifteen studies from 12 countries (Austria, Belgium, Denmark, France, Germany, Greece, Israel, Luxembourg, Slovenia, Spain, Sweden, and the United Kingdom) were included in the BPA Study protocol developed within the European Joint Programme HBM4EU. Seventy variables related to the BPA exposure were collected through a rigorous post-harmonization process. Linear mixed regression models were used to investigate the determinants of total urine BPA in the combined population. RESULTS: Total BPA was quantified in 85-100 % of women in 14 out of 15 contributing studies. Only the Austrian PBAT study (Western Europe), which had a limit of quantification 2.5 to 25-fold higher than the other studies (LOQ=2.5 µg/L), found total BPA in less than 5 % of the urine samples analyzed. The geometric mean (GM) of total urine BPA ranged from 0.77 to 2.47 µg/L among the contributing studies. The lowest GM of total BPA was observed in France (Western Europe) from the ELFE subset (GM=0.77 µg/L (0.98 µg/g creatinine), n = 1741), and the highest levels were found in Belgium (Western Europe) and Greece (Southern Europe), from DEMOCOPHES (GM=2.47 µg/L (2.26 µg/g creatinine), n = 129) and HELIX-RHEA (GM=2.47 µg/L (2.44 µg/g creatinine), n = 194) subsets, respectively. One hundred percent of women in 14 out of 15 data collections in this study exceeded the health-based human biomonitoring guidance value for the general population (HBM-GVGenPop) of 0.0115 µg total BPA/L urine derived from the updated EFSA's BPA TDI. Variables related to the measurement of total urine BPA and those related to the main socio-demographic characteristics (age, height, weight, education, smoking status) were collected in almost all studies, while several variables related to BPA exposure factors were not gathered in most of the original studies (consumption of beverages contained in plastic bottles, consumption of canned food or beverages, consumption of food in contact with plastic packaging, use of plastic film or plastic containers for food, having a plastic floor covering in the house, use of thermal paper…). No clear determinants of total urine BPA concentrations among European women were found. A broader range of data planned for collection in the original questionnaires of the contributing studies would have resulted in a more thorough investigation of the determinants of BPA exposure in European women. CONCLUSION: This study highlights the urgent need for action to further reduce exposure to BPA to protect the population, as is already the case in the European Union. The study also underscores the importance of pre-harmonizing HBM design and data for producing comparable data and interpretable results at a European-wide level, and to increase HBM uptake by regulatory agencies.

Blood levels of 21 metals and metalloids in riverside villagers of the Brazilian Amazon: A human biomonitoring study with associations with sociodemographic, dietary, and lifestyle factors.

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.

Mono-n-hexyl phthalate: exposure estimation and assessment of health risks based on levels found in human urine samples.

Mono-n-hexyl phthalate (MnHexP) is a primary metabolite of di-n-hexyl phthalate (DnHexP) and other mixed side-chain phthalates that was recently detected in urine samples from adults and children in Germany. DnHexP is classified as toxic for reproduction category 1B in Annex VI of Regulation (EC) 1272/2008 and listed in Annex XIV of the European chemical legislation REACH; thereby, its use requires an authorisation. Health-based guidance values for DnHexP are lacking and a full-scale risk assessment has not been carried out under REACH. The detection of MnHexP in urine samples raises questions about the sources of exposure and concerns of consumer safety. Here, we propose the calculation of a provisional oral tolerable daily intake value (TDI) of 63 µg/kg body weight/day for DnHexP and compare it to intake levels corresponding to levels of MnHexP found in urine. The resulting mean intake levels correspond to less than 0.2% of the TDI, and maximum levels to less than 5%. The TDI was derived by means of an approximate probabilistic analysis using the credible interval from benchmark dose modelling of published ex vivo data on reduced foetal testosterone production in rats. Thus, for the dose associated to a 20% reduction in testosterone production, a lower and upper credible interval of 14.9 and 30.0 mg/kg bw/day, respectively, was used. This is considered a conservative approach, since apical developmental endpoints (e.g. changed anogenital distance) were only observed at higher doses. In addition, we modelled various scenarios of the exposure to the precursor substance DnHexP from different consumer products, taking measured contamination levels into account, and estimated systemic exposure doses. Of the modelled scenarios including the application of sunscreen (as a lotion or pump spray), the use of lip balm, and the wearing of plastic sandals, and considering conservative assumptions, the use of DnHexP-contaminated sunscreen was highlighted as a major contributing factor. A hypothetical calculation using conservative assumptions for the latter resulted in a margin of safety in relation to the lower credible interval of 3267 and 1007 for adults and young children, respectively. Most importantly, it was found that only a fraction of the TDI is reached in all studied exposure scenarios. Thus, with regard to the reported DnHexP exposure, a health risk can be considered very unlikely.

Monitoring of per- and polyfluoroalkyl substances (PFAS) in human blood samples collected in three regions with known PFAS releases in the environment and three control regions in South Germany.

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.

Temporal trends of per- and polyfluoroalkyl substances concentrations: Insights from Australian human biomonitoring 2002-2021 and the U.S. NHANES programs 2003-2018.

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.

Toxicokinetics of 2-ethylhexyl salicylate (EHS) and its seven metabolites in humans after controlled single dermal exposure to EHS.

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.

Pesticide residues and polyphenols in urine - A combined LC-HRMS screening to reveal intake patterns.

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.

Blood levels of metallic chemical element exposure patterns and associated factors in a population living in an Industrial District in Brazil.

AIM: to estimate the level of metallic chemical elements in the population living in the Steel company vicinity in Santa Cruz, Rio de Janeiro, Brazil; and estimate the association between exposure to the Steel company and the blood metals concentrations patterns. METHOD: A cross-sectional study was carried out on 463 individuals aged 18+ years old residing 1+ years in the Steel company vicinity. Mg, Be, Co, Ba, Ni, Cd, Al, and Pb were assessed in blood by DRC-ICP-MS. Metallic chemical element concentration patterns were obtained by exploratory factor analysis in the studied population. Exposure was set as the distance (Km) from each participant's residence to the Steel company in Santa Cruz, georeferenced by GPS. The outcome was set as the positive factor loadings in the factor analysis, including Mg and Be (Factor-1), Co, Ba, and Ni (Factor-2), Cd, Al, and Pb (Factor-4). Crude and adjusted OR, and their respective 95 %CI, were estimated to explore associations between independent variables and the exposures to metallic elements positively associated with the factors using polychotomous logistic regression. RESULTS: A reduction of 19 % was found between each km distance from the residence and the Steel company and P50 concentration of Cd, Al, and Pb (ORP50=0.81; 95 %CI:0.67-0.97), after adjusting by age, sex, and smoking. No statistically significant associations were observed for the distance from residences and the Steel company, after adjusting for age, gender, having a domestic vegetable garden and chewing gum for Mg and Be concentrations (Factor-1) (ORP50=0.84; 95 %CI:0.70-1.01; ORP75=1.10; 95 %CI:0.91-1.34); nor for Co, Ba and Ni (Factor-2) blood concentrations(ORP50=1.10; 95 %CI:0.91-1.33; ORP75=1.03; 95 %CI:0.84-1.26), in the adjusted analysis. CONCLUSIONS: For each Km distance from residences to the Steel company, a 19 % reduction in the risk of Cd, Al, and Pb blood concentration was observed in the population living in Santa Cruz, Rio de Janeiro, Brazil.

Validation of a UPLC-MS/MS Method for Multi-Matrix Biomonitoring of Alternaria Toxins in Humans.

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.

Blood mercury mediates the associations between fish consumption and serum uric acid levels among Chinese adults: A nationally representative study.

Fish consumption can increase purine load in human body, and the enrichment of mercury in fish may affect the glomerular filtration function, both resulting in increased serum uric acid (SUA) levels. The data of blood mercury (BHg), fish consumption frequency and SUA levels of 7653 participants aged 18 years or older was from China National Human Biomonitoring (2017-2018). The associations between fish consumption frequency, ln-transformed BHg and SUA levels were explored through weighted multiple linear regressions. The mediating effect of BHg levels between fish consumption frequency and SUA levels was evaluated by mediation analysis. We found that both the fish consumption frequency and BHg were positively associated with SUA levels in both sexes. Compared to participants who had never consumed fish, participants who consumed fish once a week or more had higher SUA levels [ß (95% confidence interval, CI): 20.39 (2.16, 38.62) in males; ß (95% CI): 10.06 (0.76, 19.37) in females] and ln-transformed BHg [ß (95% CI): 0.97 (0.61, 1.34) in males; ß (95% CI): 0.84 (0.63, 1.05) in females]. Each 1-unit increase in ln-transformed BHg, the SUA levels rose by 4.78 (95% CI: 0.01, 9.54) µmol/L for males and 3.81 (95% CI: 1.60, 6.03) µmol/L for females. The association between fish consumption with SUA levels was mediated by ln-transformed BHg with the percent mediated of 34.66% in males and 26.58% in females. It revealed that BHg played mediating roles in the elevation of SUA levels caused by fish consumption. This study's findings could promote the government to intervene in mercury pollution in fish, so as to ensure the safety of fish consumption.

Comparison of DNA damage in fresh and frozen blood samples: implications for the comet assay in human biomonitoring studies.

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.

New metabolites of 2-ethylhexyl salicylate in human urine after simulated real-life dermal sunscreen application.

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.