Current state and future perspectives on de facto population markers for normalization in wastewater-based epidemiology: A systematic literature review.

Wastewater-based epidemiology (WBE) and wastewater surveillance have become a valuable complementary data source to collect information on community-wide exposure through the measurement of human biomarkers in influent wastewater (IWW). In WBE, normalization of data with the de facto population that corresponds to a wastewater sample is crucial for a correct interpretation of spatio-temporal trends in exposure and consumption patterns. However, knowledge gaps remain in identifying and validating suitable de facto population biomarkers (PBs) for refinement of WBE back-estimations. WBE studies that apply de facto PBs (including hydrochemical parameters, utility consumption data sources, endo- and exogenous chemicals, biological biomarkers and signalling records) for relative trend analysis and absolute population size estimation were systematically reviewed from three databases (PubMed, Web of Science, SCOPUS) according to the PRISMA guidelines. We included in this review 81 publications that accounted for daily variations in population sizes by applying de facto population normalization. To date, a wide range of PBs have been proposed for de facto population normalization, complicating the comparability of normalized measurements across WBE studies. Additionally, the validation of potential PBs is complicated by the absence of an ideal external validator, magnifying the overall uncertainty for population normalization in WBE. Therefore, this review proposes a conceptual tier-based cross-validation approach for identifying and validating de facto PBs to guide their integration for i) relative trend analysis, and ii) absolute population size estimation. Furthermore, this review also provides a detailed evaluation of the uncertainty observed when comparing different de jure and de facto population estimation approaches. This study shows that their percentual differences can range up to ±200 %, with some exceptions showing even larger variations. This review underscores the need for collaboration among WBE researchers to further streamline the application of de facto population normalization and to evaluate the robustness of different PBs in different socio-demographic communities.

Level of BPA contamination in resin composites determines BPA release.

OBJECTIVES: Resin composites may release bisphenol A (BPA) due to impurities present in the monomers. However, there is a lack of knowledge regarding the leaching characteristics of BPA from resin composites. Therefore, experimental resin composites were prepared with known amounts of BPA. The objective of this study was (1) to determine which amount of BPA initially present in the material leaches out in the short term and, (2) how this release is influenced by the resin composition. METHODS: BPA (0, 0.001, 0.01, or 0.1 wt%) was added to experimental resin composites containing 60 mol% BisGMA, BisEMA(3), or UDMA, respectively, as base monomer and 40 mol% TEGDMA as diluent monomer. Polymerized samples (n = 5) were immersed at 37 °C for 7 days in 1 mL of water, which was collected and refreshed daily. BPA release was quantified with UPLC-MS/MS after derivatization with pyridine-3-sulfonyl chloride. RESULTS: Between 0.47 to 0.67 mol% of the originally added BPA eluted from the resin composites after 7 days. Similar elution trends were observed irrespective of the base monomer. Two-way ANOVA showed a significant effect of the base monomer on BPA release, but the differences were small and not consistent. SIGNIFICANCE: The released amount of BPA was directly proportional to the quantity of BPA present in the resin composite as an impurity. BPA release was mainly diffusion-based, while polymer composition seemed to play a minor role. Our results underscore the importance for manufacturers only to use monomers of the highest purity in dental resin composites to avoid unnecessary BPA exposure in patients.

Endocrine disrupting chemicals in children's and their parents' urine: Is the exposure related to the Chinese and Western lifestyle?

Children are known to be more vulnerable to exposure to endocrine-disrupting chemicals (EDCs) compared to adults, but evaluating the exposure pathways can be challenging. This research employed target and non-target analysis (NTA) to examine the exposure characteristics of EDCs in spot urine samples collected from 46 children's (aged 3-12 years) and their parents in Hong Kong (Chinese/Western lifestyle) and Guangzhou (mainly Chinese lifestyle). The results revealed that the geometric mean concentrations of phthalate esters metabolites (mPAEs) and bisphenols (BPs) in children's urine were 127.3 µg/gcrea and 2.5 µg/gcrea in Guangzhou, and 93.7 µg/gcrea and 2.9 µg/gcrea in Hong Kong, respectively, which were consistent with global levels. NTA identified a total of 1069 compounds, including 106 EDCs, commonly detected in food, cosmetics, and drugs. Notable regional differences were observed between Guangzhou and Hong Kong with potential sources of EDCs including dietary and cosmetic additives, toys, flooring and dust, as well as differences in lifestyles, diet, and living environment. However, age was found to significantly impact EDC exposure. The quantified EDCs (mPAEs and BPs) posed possible health risks to 60% of the children. Moreover, the presence of caffeine in children's urine, which exhibited higher detection rates in children from Hong Kong (95.6%) and Guangzhou (44.4%), warrants further attention. The sources of EDCs exposure in these regions need to be fully confirmed.

Personal environmental exposure to plasticizers and organophosphate flame retardants using silicone wristbands and urine: Patterns, comparisons, and correlations.

Plasticizers (PLs) and organophosphate flame retardants (OPFRs) are ubiquitous in the environment due to their widespread use and potential for leaching from consumer products. Environmental exposure is a critical aspect of the human exposome, revealing complex interactions between environmental contaminants and potential health effects. Silicone wristbands (SWBs) have emerged as a novel and non-invasive sampling device for assessing personal external exposure. In this study, SWBs were used as a proxy to estimate personal dermal adsorption (EDdermal) to PLs and OPFRs in Belgian participants for one week; four morning urine samples were also collected and analyzed for estimated daily intake (EDI). The results of the SWBs samples showed that all the participants were exposed to these chemicals, and the exposure was found to be highest for the legacy and alternative plasticizers (LP and AP), followed by the legacy and emerging OPFRs (LOPFR and EOPFR). In urine samples, the highest levels were observed for metabolites of diethyl phthalate (DEP), di-isobutyl phthalate (DiBP) and di-n-butyl phthalate (DnBP) among LPs and di(2-ethylhexyl) terephthalate (DEHT) for APs. Outliers among the participants indicated that there were other sources of exposure that were not identified. Results showed a significant correlation between EDdermal and EDI for DiBP, tris (2-butoxyethyl) phosphate (TBOEP) and triphenyl phosphate (TPhP). These correlations indicated their suitability for predicting exposure via SWB monitoring for total chemical exposure. The results of this pilot study advance our understanding of SWB sampling and its relevance for predicting aggregate environmental chemical exposures, while highlighting the potential of SWBs as low-cost, non-invasive personal samplers for future research. This innovative approach has the potential to advance the assessment of environmental exposures and their impact on public health.

Urinary phthalate/DINCH metabolites associations with kisspeptin and reproductive hormones in teenagers: A cross-sectional study from the HBM4EU aligned studies.

BACKGROUND: Exposure to phthalate/DINCH metabolites can induce human reproductive toxicity, however, their endocrine-disrupting mechanisms are not fully elucidated. OBJECTIVE: To investigate the association between concentrations of phthalate/DINCH metabolites, serum kisspeptin, and reproductive hormones among European teenagers from three of the HBM4EU Aligned Studies. METHODS: In 733 Belgian (FLEHS IV study), Slovak (PCB cohort follow-up), and Spanish (BEA study) teenagers, ten phthalate and two DINCH metabolites were measured in urine by high-performance liquid chromatography-tandem mass spectrometry. Serum kisspeptin (kiss54) protein, follicle-stimulating hormone (FSH), total testosterone (TT), estradiol (E2), and sex hormone-binding globulin (SHBG) levels were measured by immunosorbent assays. Free Androgen Index (FAI) was calculated as a proxy of free testosterone. Adjusted sex-stratified linear regression models for individual studies, mixed effect models (LME) accounting for random effects for pooled studies, and g-computation and Bayesian kernel machine regression (BKMR) models for the phthalate/DINCH mixture were performed. RESULTS: The LME suggested that each IQR increase in ln-transformed levels of several phthalates was associated with lower kisspeptin [MnBP: %change (95%CI): -2.8 (-4.2;-0.4); MEHP: -1.4 (-3.4,0.2)] and higher FSH [∑DINP: 11.8 (-0.6;25.1)] levels in females from pooled studies. G-computation showed that the phthalates/DINCH mixture was associated with lower kisspeptin [-4.28 (-8.07;-0.34)] and higher FSH [22.13 (0.5;48.4)] also in females; BKMR showed similar although non-significant pattern. In males, higher phthalates metabolites [MEHP: -12.22 (-21.09;-1.18); oxo-MEHP: -12.73 (-22.34;-1.93)] were associated with lower TT and FAI, although higher DINCH [OH-MINCH: 16.31 (6.23;27.35), cx-MINCH: 16.80 (7.03;27.46), ∑DINCH: 17.37 (7.26;29.74)] were associated with higher TT levels. No mixture associations were found in males. CONCLUSION: We observed sex-specific associations between urinary concentrations of phthalate/DINCH metabolites and the panel of selected effect biomarkers (kisspeptin and reproductive hormones). This suggests that exposure to phthalates would be associated with changes in kisspeptin levels, which would affect the HPG axis and thus influence reproductive health. However, further research is needed, particularly for phthalate replacements such as DINCH.

Serum untargeted lipidomic characterization in a general Chinese cohort with residual per-/polyfluoroalkyl substances by liquid chromatography-drift tube ion mobility-mass spectrometry.

Per- and polyfluoroalkyl substances (PFAS) remain controversial due to their high persistency and potential human toxicity. Although occupational exposure to PFAS has been widely investigated, the implications of PFAS occurrence in the general population remain to be unraveled. Considering that serum from most people contains PFAS, the aim of this study was to characterize the lipidomic profile in human serum from a general cohort (n = 40) with residual PFAS levels. The geometric means of ∑PFAS (11.8 and 4.4 ng/mL) showed significant differences (p < 0.05) for the samples with the highest (n = 20) and lowest (n = 20) concentrations from the general population respectively. Reverse-phase liquid chromatography coupled to drift tube ion mobility and high-resolution mass spectrometry using dual polarity ionization was used to characterize the lipid profile in both groups. The structural elucidation involved the integration of various parameters, such as retention time, mass-to-charge ratio, tandem mass spectra and collision cross section values. This approach yielded a total of 20 potential biomarkers linked to the perturbed glycerophospholipid metabolism, energy metabolism and sphingolipid metabolism. Among these alterations, most lipids were down-regulated and some specific lipids (PC 36:5, PC 37:4 and PI O-34:2) exhibited a relatively strong Spearman correlation and predictive capacity for PFAS contamination. This study could support further toxicological assessments and mechanistic investigations into the effects of PFAS exposure on the lipidome.

Ongoing exposure to endocrine disrupting phthalates and alternative plasticizers in neonatal intensive care unit patients.

Due to endocrine disrupting effects, di-(2-ethylhexyl) phthalate (DEHP), a plasticizer used to soften plastic medical devices, was restricted in the EU Medical Devices Regulation (EU MDR 2017/745) and gradually replaced by alternative plasticizers. Neonates hospitalized in the neonatal intensive care unit (NICU) are vulnerable to toxic effects of plasticizers. From June 2020 to August 2022, urine samples (n = 1070) were repeatedly collected from premature neonates (n = 132, 4-10 samples per patient) born at <31 weeks gestational age and/or <1500 g birth weight in the Antwerp University Hospital, Belgium. Term control neonates (n = 21, 1 sample per patient) were included from the maternity ward. Phthalate and alternative plasticizers' metabolites were analyzed using liquid-chromatography coupled to tandem mass spectrometry. Phthalate metabolites were detected in almost all urine samples. Metabolites of alternative plasticizers, di-(2-ethylhexyl)-adipate (DEHA), di-(2-ethylhexyl)-terephthalate (DEHT) and cyclohexane-1,2-dicarboxylic-di-isononyl-ester (DINCH), had detection frequencies ranging 30-95 %. Urinary phthalate metabolite concentrations were significantly higher in premature compared to control neonates (p = 0.023). NICU exposure to respiratory support devices and blood products showed increased phthalate metabolite concentrations (p < 0.001). Phthalate exposure increased from birth until four weeks postnatally. The estimated phthalate intake exceeded animal-derived no-effect-levels (DNEL) in 10 % of samples, with maximum values reaching 24 times the DNEL. 29 % of premature neonates had at least once an estimated phthalate intake above the DNEL. Preterm neonates are still exposed to phthalates during NICU stay, despite the EU Medical Devices Regulation. NICU exposure to alternative plasticizers is increasing, though currently not regulated, with insufficient knowledge on their hazard profile.

Investigation of in vitro biotransformation of tris (1-chloro-2-propyl) phosphate and confirmation in human urine.

Tris (1-chloro-2-propyl) phosphate (TCIPP) is one of the major organophosphate flame retardants present in the indoor and outdoor environment. Knowledge of biotransformation pathways is important to elucidate potential bioavailability and toxicity of TCIPP and to identify relevant biomarkers. This study aimed to identify TCIPP metabolites through in vitro human metabolism assays and finally to confirm these findings in urine samples from an occupationally exposed population to propose new biomarkers to accurately monitor exposure to TCIPP. TCIPP was incubated with human liver microsomes and human liver cytosol to identify Phase I and Phase II metabolites, by liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). Using a suspect-screening approach, the established biomarkers bis (1-chloro-2-propyl) hydrogen phosphate (BCIPP) and 1-hydroxy-2-propyl bis (1-chloro-2-propyl) phosphate (BCIPHIPP) were identified. In addition, carboxyethyl bis (1-chloro-2-propyl) phosphate (TCIPP-M1), bis (1-chloropropan-2-yl) (-oxopropan-2-yl) phosphate (TCIPP-M2) and 1-chloro-3-hydroxypropan-2-yl bis (1-chloropropan-2-yl) phosphate (TCIPP-M3) were identified. TCIPP-M2, an intermediate product, was not reported before in literature. In urine samples, apart from BCIPP and BCIPHIPP, TCIPP-M1 and TCIPP-M3 were identified for the first time. Interestingly, BCIPP showed the lowest detection frequency, likely due to the poor sensitivity for this compound. Therefore, TCIPP-M1 and TCIPP-M3 could serve as potential additional biomarkers to more efficiently monitor TCIPP exposure in humans.

Refining the correction factor for a better monitoring of antidepressant use by wastewater-based epidemiology: A case study of amitriptyline.

Wastewater-based epidemiology (WBE) is proposed as a cost-effective approach to objectively monitor the antidepressant use but it requires more accurate correction factors (CF) than what had been used in previous studies. Amitriptyline is a popular prescription medicine for treating depression and nerve pain, which could be prone to misuse and need monitoring. The CF of amitriptyline employed in previous WBE studies varied from 10 to 100, leading to substantial disparities between WBE estimates and expected mass of antidepressants in wastewater. Hence, this study aimed to take amitriptyline as a case study and refine the CF by correlating mass loads measured in wastewater from 12.2 million inhabitants collected during the 2016 Census with corresponding annual sales data. The triangulation of WBE data and sales data resulted in a newly-derived CF of 7, which is significantly different from the CF values used in previous studies. The newly derived CF was applied to a secondary, multi-year (2017 to 2020) WBE dataset for validation against sales data in the same period, demonstrating the estimated amitriptyline use (380 ± 320 mg/day/1000 inhabitants) is consistent with sales data (450 ± 190 mg/day/1000 inhabitants). When we applied the new CF to previous studies, the wastewater consumption loads matched better to prescription data than previous WBE estimations. The refined CF of amitriptyline can be used in future WBE studies to improve the accuracy of the consumption estimates.

Influent wastewater analysis to investigate emerging trends of new psychoactive substances use in Europe.

Wastewater-based epidemiology (WBE) can provide objective and timely information on the use of new psychoactive substances (NPS), originally designed as legal alternatives of internationally controlled drugs. NPS have rapidly emerged on the global drug market, posing a challenge to drug policy and constituting a risk to public health. In this study, a WBE approach was applied to monitor the use of more than 300 NPS, together with fentanyl and its main metabolite norfentanyl, in influent wastewater collected from 12 European cities during March-June 2021. Quantitative and qualitative analysis of NPS in composite 24 h influent wastewater samples were based on solid phase extraction and liquid chromatography-mass spectrometry. In-sample stability tests demonstrated the suitability of most investigated biomarkers, except for a few synthetic opioids, synthetic cannabinoids and phenetylamines. Fentanyl, norfentanyl and eight NPS were quantified in influent wastewater and at least three substances were found in each city, demonstrating their use in Europe. N,N-dimethyltryptamine and 3-methylmethcathinone (3-MMC) were the most common NPS found, with the latter having the highest mass loads (up to 24.8 mg/day/1000 inhabitants). Seven additional substances, belonging to five categories of NPS, were identified in different cities. Spatial trends of NPS use were observed between cities and countries, and a changing weekly profile of use was observed for 3-MMC. WBE is a useful tool to rapidly evaluate emerging trends of NPS use, complementing common indicators (i.e. population surveys, seizures) and helping to establish measures for public health protection.

Innovative analytical methodologies for characterizing chemical exposure with a view to next-generation risk assessment.

The chemical burden on the environment and human population is increasing. Consequently, regulatory risk assessment must keep pace to manage, reduce, and prevent adverse impacts on human and environmental health associated with hazardous chemicals. Surveillance of chemicals of known, emerging, or potential future concern, entering the environment-food-human continuum is needed to document the reality of risks posed by chemicals on ecosystem and human health from a one health perspective, feed into early warning systems and support public policies for exposure mitigation provisions and safe and sustainable by design strategies. The use of less-conventional sampling strategies and integration of full-scan, high-resolution mass spectrometry and effect-directed analysis in environmental and human monitoring programmes have the potential to enhance the screening and identification of a wider range of chemicals of known, emerging or potential future concern. Here, we outline the key needs and recommendations identified within the European Partnership for Assessment of Risks from Chemicals (PARC) project for leveraging these innovative methodologies to support the development of next-generation chemical risk assessment.

Residential energy transition and chronic respiratory diseases.

Obtaining clean energy is of prime importance for planetary health and sustainable development. We aimed to assess the association between residential energy transition and the risk of chronic respiratory diseases. Using data from the Global Health Observatory and Global Burden of Diseases, Injuries, and Risk Factors Study, we delineated the spatial distribution and temporal trends of the population using clean fuels for cooking at a global scale. In the China Health and Retirement Longitudinal Study, we performed rigorous and well-structured multistage analyses incorporating both cross-sectional and prospective data analyses to examine the associations between solid fuel use, residential energy transition, duration of solid fuel use, and the risk of chronic respiratory diseases. Despite great progress, huge disparities in access to clean energy persist globally. Residential energy transition was associated with a lower risk of chronic respiratory diseases. In the period of 2011-2013, compared with persistent solid fuel users, both participants who switched from solid to clean fuels (adjusted risk ratio [RR] 0.78, 95% confidence interval [CI] 0.62-0.98) and persistent clean fuel users (adjusted RR 0.71, 95% CI 0.57-0.89) had significantly lower risk of chronic respiratory diseases (p < 0.001 for trend). Consistent associations were observed in the period of 2011-2015 and 2011-2018. Household energy transition from solid to clean fuels could reduce the risk of chronic respiratory diseases. This is a valuable lesson for policy-makers and the general public to accelerate energy switching to alleviate the burden of chronic respiratory diseases and achieve health benefits, particularly in low- and middle-income countries.

Prenatal exposure to mixtures of per- and polyfluoroalkyl substances and organochlorines affects cognition in adolescence independent of postnatal exposure.

BACKGROUND: Studies on cognitive and neurodevelopmental outcomes have shown inconsistent results regarding the association with prenatal exposure to perfluoroalkyl substance (PFAS) and organochlorines. Assessment of mixture effects of correlated chemical exposures that persist in later life may contribute to the unbiased evaluation and understanding of dose-response associations in real-life exposures. METHODS: For a subset of the 4th Flemish Environment and Health Study (FLEHS), concentrations of four PFAS and six organochlorines were measured in respectively 99 and 153-160 cord plasma samples and 15 years later in adolescents' peripheral serum by Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS). Sustained and selective attention were measured at 14-15 years with the Continuous Performance Test (CPT) and Stroop Test as indicators of potential neurodevelopmental deficits. Quantile g-computation was applied to assess the joint associations between prenatal exposure to separate and combined groups of PFAS and organochlorines and performance in the CPT and Stroop Test at adolescence. Subsequently, individual effects of each chemical compound were analyzed in mixed effects models with two sets of covariates. Analytical data at birth and at the time of cognitive assessment allowed for off-setting postnatal exposure. RESULTS: In mixtures analysis, a simultaneous one-quantile increase in the natural log-transformed values of PFAS and organochlorines combined was associated with a decrease in the mean reaction time (RT) and the reaction time variability (RTV) in the CPT (ß = -15.54, 95% CI:-29.64, -1.45, and ß = -7.82, 95% CI: -14.97, -0.67 respectively) and for the mixture of PFAS alone with RT (ß = -11.94, 95% CI: -23.29, -0.60). In the single pollutant models, these results were confirmed for the association between perfluorohexanesulfonate (PFHxS) with RT (ß = -17.95, 95% CI = -33.35, -2.69) and hexachlorobenzene with RTV in the CPT (ß = -5.78, 95% CI: -10.39, -0.76). Furthermore, the participants with prenatal exposure above the limit of quantification for perfluorononanoic acid (PFNA) had a significantly shorter RT and RTV in the CPT (ß = -23.38, 95% CI: -41.55, -5.94, and ß = -9.54, 95% CI: -19.75, -0.43, respectively). CONCLUSION: Higher prenatal exposure to a PFAS mixture and a mixture of PFAS and organochlorines combined was associated with better sustained and selective attention during adolescence. The associations seemed to be driven by PFHxS and were not linked to exposure levels at the time of assessment.

Co-exposure to 55 endocrine-disrupting chemicals linking diminished sperm quality: Mixture effect, and the role of seminal plasma docosapentaenoic acid.

Isolated effects of single endocrine-disrupting chemicals (EDCs) on male reproductive health have been studied extensively, but their mixture effect remains unelucidated. Previous research has suggested that consuming diet enriched in omega-3 polyunsaturated fatty acids (PUFA) might be beneficial for reproductive health, whether omega-3 PUFA could moderate the effect of EDCs mixture on semen quality remains to be explored. In this study of 155 male recruited from a reproductive health center in China, we used targeted-exposomics to simultaneously measure 55 EDCs in the urine for exposure burden. Regression analyses were restricted to highly detected EDCs (≥55%, n = 34), and those with consistently elevated risk were further screened and brought into mixture effect models (Bisphenol A, ethyl paraben, methyl paraben [MeP], benzophenone-1 [BP1], benzophenone-3, mono(3-carboxypropyl) phthalate [MCPP]). Bayesian Kernel Machine Regression (BKMR) and quantile-based g-computation (QGC) models demonstrated that co-exposure to top-ranked EDCs was related to reduced sperm total (ß = -0.18, 95%CI: -0.29 - -0.07, P = 0.002) and progressive motility (ß = -0.27, 95%CI: -0.43 - -0.10, P = 0.002), but not to lower semen volume. BP1, MeP and MCPP were identified as the main effect driver for deteriorated sperm motion parameters using mixture model analyses. Seminal plasma fatty acid profiling showed that high omega-3 PUFA status, notably elevated docosapentaenoic acid (DPA, C22:5n-3) status, moderated the association between MCPP and sperm motion parameters (total motility: ß = 0.26, 95%CI: 0.01 - -0.51, Pinteraction = 0.047; progressive motility: ß = 0.64, 95%CI: 0.23 - 1.05, Pinteraction = 0.003). Co-exposure to a range of EDCs is mainly associated with deteriorated sperm quality, but to a lesser extent on sperm quantity, high seminal plasma DPA status might be protective against the effect. Our work emphasizes the importance of exposomic approach to assess chemical exposures and highlighted a new possible intervention target for mitigating the potential adverse effect of EDCs on semen quality.

Detection of Bromochloro Alkanes in Indoor Dust Using a Novel CP-Seeker Data Integration Tool.

Bromochloro alkanes (BCAs) have been manufactured for use as flame retardants for decades, and preliminary environmental risk screening suggests they are likely to behave similarly to polychlorinated alkanes (PCAs), subclasses of which are restricted as Stockholm Convention Persistent Organic Pollutants (POPs). BCAs have rarely been studied in the environment, although some evidence suggests they may migrate from treated-consumer materials into indoor dust, resulting in human exposure via inadvertent ingestion. In this study, BCA-C14 mixture standards were synthesized and used to validate an analytical method. This method relies on chloride-enhanced liquid chromatography-electrospray ionization-Orbitrap-high resolution mass spectrometry (LC-ESI-Orbitrap-HRMS) and a novel CP-Seeker integration software package for homologue detection and integration. Dust sample preparation via ultrasonic extraction, acidified silica cleanup, and fractionation on neutral silica cartridges was found to be suitable for BCAs, with absolute recovery of individual homologues averaging 66 to 78% and coefficients of variation ≤10% in replicated spiking experiments (n = 3). In addition, a total of 59 indoor dust samples from six countries, including Australia (n = 10), Belgium (n = 10), Colombia (n = 10), Japan (n = 10), Thailand (n = 10), and the United States of America (n = 9), were analyzed for BCAs. BCAs were detected in seven samples from the U.S.A., with carbon chain lengths of C8, C10, C12, C14, C16, C18, C24 to C28, C30 and C31 observed overall, though not detected in samples from any other countries. Bromine numbers of detected homologues in the indoor dust samples ranged Br1-4 as well as Br7, while chlorine numbers ranged Cl2-11. BCA-C18 was the most frequently detected, observed in each of the U.S.A. samples, while the most prevalent degrees of halogenation were homologues of Br2 and Cl4-5. Broad estimations of BCA concentrations in the dust samples indicated that levels may approach those of other flame retardants in at least some instances. These findings suggest that development of quantification strategies and further investigation of environmental occurrence and health implications are needed.

HBM4EU E-waste study: Assessing persistent organic pollutants in blood, silicone wristbands, and settled dust among E-waste recycling workers in Europe.

E-waste recycling is an increasingly important activity that contributes to reducing the burden of end-of-life electronic and electrical apparatus and allows for the EU's transition to a circular economy. This study investigated the exposure levels of selected persistent organic pollutants (POPs) in workers from e-waste recycling facilities across Europe. The concentrations of seven polychlorinated biphenyls (PCBs) and eight polybrominated diphenyl ethers (PBDEs) congeners were measured by GC-MS. Workers were categorized into five groups based on the type of e-waste handled and two control groups. Generalized linear models were used to assess the determinants of exposure levels among workers. POPs levels were also assessed in dust and silicone wristbands (SWB) and compared with serum. Four PCB congeners (CB 118, 138, 153, and 180) were frequently detected in serum regardless of worker's category. With the exception of CB 118, all tested PCBs were significantly higher in workers compared to the control group. Controls working in the same company as occupationally exposed (Within control group), also displayed higher levels of serum CB 180 than non-industrial controls with no known exposures to these chemicals (Outwith controls) (p < 0.05). BDE 209 was the most prevalent POP in settled dust (16 µg/g) and SWB (220 ng/WB). Spearman correlation revealed moderate to strong positive correlations between SWB and dust. Increased age and the number of years smoked cigarettes were key determinants for workers exposure. Estimated daily intake through dust ingestion revealed that ΣPCB was higher for both the 50th (0.03 ng/kg bw/day) and 95th (0.09 ng/kg bw/day) percentile exposure scenarios compared to values reported for the general population. This study is one of the first to address the occupational exposure to PCBs and PBDEs in Europe among e-waste workers through biomonitoring combined with analysis of settled dust and SWB. Our findings suggest that e-waste workers may face elevated PCB exposure and that appropriate exposure assessments are needed to establish effective mitigation strategies.

Stable isotope ratios and current-use pesticide levels in edible insects: Implications on chemical food safety.

In the past years, the European Union (EU) has added edible insects to the list of novel foods, allowing an increasing number of insect-based products into the European market. With insects gaining more popularity in the Western world, it is crucial to investigate their chemical food safety. This study aimed at investigating possible isotopic patterns in different edible insect species (n = 52) from Asia, Africa and Europe using stable isotope ratio analysis (SIRA) to provide a framework for future investigations on food authenticity and traceability. Additionally, complementary mass-spectrometric screening approaches were applied to gain a comprehensive overview of contamination levels of current-use pesticides (CUPs) in edible insects, to assess their chemical food safety. SIRA revealed significant differences between countries in δ13CVPDB- (p < 0.001) and δ15Nair- (p < 0.001) values. While it was not possible to distinguish between individual countries using principal component analysis (PCA) and linear discriminative analysis (LDA), the latter could be used to distinguish between larger geographical areas (i.e. Africa, Europe and Asia). In general, African samples had a more distinct isotopic profile compared to European and Asian samples. When comparing the isotopic compositions of samples containing pesticides with samples with no detected pesticides, differences in sulphur compositions could be observed. Additionally, LDA was able to correctly classify the presence of pesticides in a sample with 76% correct classification based on the sulphur composition. These findings show that SIRA could be a useful tool to provide a framework for future investigations on food authenticity and traceability of edible insects. A total of 26 CUPs were detected using suspect screening and an additional 30 CUPS were quantified using target analysis, out of which 9 compounds had a detection frequency higher than 30%. Most detected pesticides were below the maximum residue levels (MRLs) for meat, suggesting low contamination levels. However, dichlorvos and fipronil could be detected in the same order of magnitude as the MRLs, even in samples purchased in Europe. These findings indicate a limited chemical risk for edible insects regarding pesticide contamination. Nevertheless, the study also highlights that further and more extensive investigations are needed to give a comprehensive assessment of the chemical risk of edible insects as a novel food source in Europe. With insects recently being potentially more incorporated into daily diets, more attention should be paid to possible chemical hazards to accurately assess their risk and to ensure food safety.

Identification, semi-quantification and risk assessment of contaminants of emerging concern in Flemish indoor dust through high-resolution mass spectrometry.

Indoor dust can contribute substantially to human exposure to known and contaminants of emerging concern (CECs). Novel compounds with high structural variability and different homologues are frequently discovered through screening of the indoor environment, implying that constant monitoring is required. The present study aimed at the identification and semi-quantification of CECs in 46 indoor dust samples collected in Belgium by liquid chromatography high-resolution mass spectrometry. Samples were analyzed applying a targeted and suspect screening approach; the latter based on a suspect list containing >4000 CECs. This allowed the detection of a total of 55 CECs, 34 and 21 of which were identified with confidence level (CL) 1/2 or CL 3, respectively. Besides numerous known contaminants such as di(2-ethylhexyl) phthalate (DEHP), di(2-ethylhexyl) adipate (DEHA) or tris(2-butoxyethyl) phosphate (TBOEP) which were reported with detection frequencies (DFs) > 90%, several novel CECs were annotated. These included phthalates with differing side chains, such as decyl nonyl and decyl undecyl phthalate detected with DFs >80% and identified through the observation of characteristic neutral losses. Additionally, two novel organophosphate flame retardants not previously described in indoor dust, i.e. didecyl butoxyethoxyethyl phosphate (DDeBEEP) and bis(butoxyethyl) butyl phosphate (BBEBP), were identified. The implementation of a dedicated workflow provided semi-quantitative concentrations for a set of suspects. Such data obtained for novel phthalates were in the same order of magnitude as the concentrations observed for legacy phthalates indicating their high relevance for human exposure. From the semi-quantitative data, estimated daily intakes and resulting hazard quotients (HQs) were calculated to estimate the exposure and potential health effects. Neither of the obtained HQ values exceeded the risk threshold, indicating no expected adverse health effects.

The complementarity of phosphatidylethanol in whole blood and ethyl glucuronide in hair as biomarkers for the monitoring of alcohol use.

Monitoring long-term alcohol use and/or abstinence is essential in clinical and medico-legal cases. Analysis of ethyl glucuronide (EtG) in hair provides information on alcohol consumption over several months. However, there is a lag time between ethanol consumption, incorporation of EtG in the hair bulb and hair growing out of the scalp. Phosphatidylethanol (PEth) 16:0/18:1 analysis in whole blood has a detection window of 2-4 weeks, allowing for the detection of recent alcohol consumption. In this study, 2340 paired samples (of hair and venous whole blood from 1170 individuals) were analysed for EtG in hair (hEtG) and PEth 16:0/18:1 in venous whole blood. PEth 16:0/18:1 and hEtG results were subdivided into three categories according to the consensus of SoHT (hEtG) and PEth-NET (PEth): abstinence/low, moderate or excessive alcohol consumption. For hEtG analysis, 446 individuals presented abstinence/low alcohol consumption, of which 2% were classified as excessive alcohol users through PEth 16:0/18:1 analysis. This suggests excessive alcohol consumption in the weeks before sample collection. Out of 483 individuals classified as heavy alcohol users based on hEtG analysis, 14% showed abstinence/low alcohol consumption for PEth 16:0/18:1 analysis, implying that these subjects stopped drinking 2-4 weeks before sample collection. Our results show that the analysis of the two different biomarkers can lead to a more accurate categorisation of individuals. Therefore, we emphasize that for the retrospective investigation of alcohol use, it is necessary to include two alcohol use biomarkers with different detection windows.