Monitoring antidepressant use is important for understanding mental health treatment status in populations and detecting potential misuse. Wastewater-based epidemiology (WBE) is a cost-effective approach to conduct such monitoring but requires valid correction factors (CFs) to accurately convert wastewater mass loads into consumption estimates. Most existing CFs are calculated from pharmacokinetic studies with small cohorts and are not specifically validated for WBE purposes. This study aimed to fill this knowledge gap by calibrating and validating the CFs for 5 commonly prescribed antidepressants. CFs were calibrated by dividing corresponding geo-located sales data by wastewater mass loads from 18 wastewater treatment plants in Australia for the same 3.5-year period. The refined CFs were 9.0 for fluoxetine, 6.4 for venlafaxine, and 25 for quetiapine. For the case of racemic citalopram and the pure S-enantiomer (escitalopram), individual CFs were proposed as 2.0 and 11, respectively. To validate their applicability, the new CFs were applied to independent datasets of wastewater samples collected in Belgium (2019 to 2022) and Australia (2020) and compared with sales data. The new calibrated CFs produced more accurate wastewater-based estimates of consumption for citalopram, escitalopram, fluoxetine, venlafaxine, and quetiapine, enhancing the capability of WBE in public health surveillance.

Increasing evidence implicates prenatal exposure to di-(2-ethylhexyl) phthalate (DEHP), a common endocrine-disrupting plastic chemical, in autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). However, the underlying mechanisms are poorly understood. Here we examined whether cord blood DNA methylation, a key epigenetic marker, mediates the association between prenatal DEHP exposure and ASD/ADHD symptoms in 847 children enrolled in the Barwon Infant Study. ASD and ADHD are complex phenotypes characterised by differences at the gene regulatory network and neuronal circuit level, where heterogeneous genetic and environmental risk factors converge. Accordingly, we employed a data-driven computational strategy that helped elucidate broader functional epigenetic signatures of ASD and ADHD elicited by DEHP exposure. This included (1) a methylation profile score for DEHP exposure (MPSDEHP), and (2) an analysis of co-methylated gene networks. Causal mediation analysis demonstrated that both MPSDEHP and a DEHP-associated network of co-methylated genes mediated the effect of DEHP exposure on increased ASD and ADHD symptoms at ages 2 and 4 years (proportion of effect mediated ranged from 0.21 to 0.80). The co-methylation network was enriched for neural cell-type markers, ASD risk genes (including FOXP1, SHANK2, and PLXNB1), and targets of endocrine receptors previously linked to DEHP (including targets of the estrogen receptor ERα and the glucocorticoid receptor GR), providing biological plausibility. We validated key results in independent blood (n=66) and postmortem brain (n=40) DNA methylation datasets. These findings provide mechanistic evidence linking DEHP to ASD and ADHD symptoms and reinforce growing concerns regarding the risks of prenatal exposure. ### Competing Interest Statement The authors have declared no competing interest.

Benzotriazoles (BZTs) and benzothiazoles (BTs) are high-production-volume chemicals utilized in many different commercial products and industrial processes, such as metal corrosion inhibitors, vulcanization accelerators, plastic-associated UV stabilizers, and pharmaceutical precursors. This study assessed age, gender, and temporal trends of BZTs and BTs in deidentified surplus pathology urine samples, pooled and stratified by age, gender, and sample collection year from a general Australian population (168 pools representing 16,800 individuals). Tolyltriazole (TTri), 5,6-dimethyl-1H-benzotriazole (DMBZT), 1,3-benzothiazole (BTH), 2-hydroxybenzothiazole (2-OH-BTH), and 2-aminobenzothiazole (2-amino-BTH) were detected in >50% of the pools. TTri was frequently detected in pooled samples representing <= 45-year-olds (both genders). Concentrations of DMBZT, BTH (females), 2-OH-BTH, and 2-amino-BTH (females) increased with age significantly, with adults (>15 years old) showing higher levels than children (<= 15 years old). Gender differences in DMBZT concentrations (females > males) were observed across all sampling years and only in some for TTri (males > females: >45 years old), BTH (females > males), and 2-amino-BTH (males > females). A temporal increase in BTH, 2-OH-BTH, and 2-amino-BTH levels within the studied period (2012-2023) has been observed. Our findings suggest ongoing exposure of the Australian general population to BZTs and BTs, highlighting age, gender, and temporal trends of these compounds as measured via their urinary concentrations.

An improved understanding of the distribution of per- and polyfluoroalkyl substances (PFAS) in PFAS-impacted concrete is important for risk management and decontamination of PFAS. This study incorporates mu -X-ray fluorescence (mu -XRF) and fluorine K-edge mu -X-ray absorption near-edge structure (mu -XANES) spectroscopy to gain non-destructive insights into PFAS distribution in the impacted concrete. The mu-XRF and mu-XANES spectroscopy provided additional details on the detection of PFAS, which were not detected by the desorption electrospray ionization (DESI) imaging method conducted previously. The shorter chain PFAS were found on the top part of the concrete core (0.5 cm), and longer chain PFAS were mostly at the bottom part of the concrete core (5 cm). The inorganic fluorine fraction was also detected, and it likely hampered the detection of organic fluorine such as PFAS in the concrete. Thus, this non-destructive technique is an complementary approach to detect PFAS in contaminated concrete.

The complexity around the dynamic markets for new psychoactive substances (NPS) forces researchers to develop and apply innovative analytical strategies to detect and identify them in influent urban wastewater. In this work a comprehensive suspect screening workflow following liquid chromatography - high resolution mass spectrometry analysis was established utilising the open -source InSpectra data processing platform and the HighResNPS library. In total, 278 urban influent wastewater samples from 47 sites in 16 countries were collected to investigate the presence of NPS and other drugs of abuse. A total of 50 compounds were detected in samples from at least one site. Most compounds found were prescription drugs such as gabapentin (detection frequency 79%), codeine (40%) and pregabalin (15%). However, cocaine was the most found illicit drug (83%), in all countries where samples were collected apart from the Republic of Korea and China. Eight NPS were also identified with this protocol: 3-methylmethcathinone 11%), eutylone (6%), etizolam (2%), 3-chloromethcathinone (4%), mitragynine (6%), phenibut (2%), 25I-NBOH (2%) and trimethoxyamphetamine (2%). The latter three have not previously been reported in municipal wastewater samples. The workflow employed allowed the prioritisation of features to be further investigated, reducing processing time and gaining in confidence in their identification.

The market for illicit drugs and new psychoactive substances (NPS) has grown significantly and people attending festivals have been identified as being at high risk (high extent and frequency of substance use). Traditional public health surveillance data sources have limitations (high costs, long implementation times, and ethical issues) and wastewater-based epidemiology (WBE) can cost-effectively support surveillance efforts. Influent wastewater samples were analyzed for NPS and illicit drug consumption collected during New Year period (from 29-Dec-2021 to 4-Jan-2022) and a summer Festival (from 29-June-2022 to 12-July-2022) in a large city in Spain. Samples were analyzed for phenethylamines, cathinones, opioids, benzodiazepines, plant-based NPS, dissociatives, and the illicit drugs methamphetamine, MDA, MDMA, ketamine, heroin, cocaine, and pseudoephedrine by liquid chromatography mass spectrometry. High consumption rates of specific NPS and established illicit drugs were identified at the peak of each event. Furthermore, a dynamic change in NPS use (presence and absence of substances) was detected over a period of six months. Eleven NPS, including synthetic cathinones, benzodiazepines, plant-based NPS and dissociatives, and seven illicit drugs were found across both the New Year and summer Festival. Statistically significant differences (p < 0.05) were seen for 3-MMC (New Year vs summer Festival), eutylone (New Year vs summer Festival), cocaine (summer Festival vs normal week and summer Festival vs New Year), MDMA (New Year vs normal week and summer Festival vs normal week), heroin (summer Festival vs New Year) and pseudoephedrine (summer Festival vs New Year). This WBE study assessed the prevalence of NPS and illicit drugs at festivals following the reduction of the COVID-19 pandemic restrictions highlighting the high use of specific substances at the peak of each event. This approach identified in a costeffective and timely manner without any ethical issues the most used drugs and changes in use patterns and, thus, can complement public health information.

BACKGROUND:Per- and polyfluoroalkyl substances (PFAS) have been associated with higher cholesterol and liver function markers in some studies, but the evidence for specific cardiometabolic conditions has been inconclusive. OBJECTIVES:We quantified the associations of single and combined PFAS with cardiometabolic markers and conditions in a cross-sectional study of three Australian communities with PFAS-contaminated water from the historical use of aqueous film-forming foam in firefighting activities, and three comparison communities. METHODS:Participants gave blood samples for measurement of nine PFAS, four lipids, six liver function markers, and completed a survey on sociodemographic characteristics and eight cardiometabolic conditions. We estimated differences in mean biomarker concentrations per doubling in single PFAS concentrations (linear regression) and per interquartile range increase in the PFAS mixture (Bayesian kernel machine regression). We estimated prevalence ratios of biomarker concentrations outside reference limits and self-reported cardiometabolic conditions (Poisson regression). RESULTS:We recruited 881 adults in exposed communities and 801 in comparison communities. We observed higher mean total cholesterol with higher single and mixture PFAS concentrations in blood serum (e.g., 0.18 mmol/L, 95% credible interval -0.06 to 0.42, higher total cholesterol concentrations with an interquartile range increase in all PFAS concentrations in Williamtown, New South Wales), with varying certainty across communities and PFAS. There was less consistency in direction of associations for liver function markers. Serum perfluorooctanoic acid (PFOA) concentrations were positively associated with the prevalence of self-reported hypercholesterolemia in one of three communities, but PFAS concentrations were not associated with self-reported type II diabetes, liver disease, or cardiovascular disease. DISCUSSION:Our study is one of few that has simultaneously quantified the associations of blood PFAS concentrations with multiple biomarkers and cardiometabolic conditions in multiple communities. Our findings for total cholesterol were consistent with previous studies; however, substantial uncertainty in our estimates and the cross-sectional design limit causal inference.

With wastewater surveillance being implemented worldwide to aid in managing coronavirus disease 2019 (COVID-19), there is a need to understand the fate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in sewer systems. Here we employed a sewer reactor to investigate sorption, decay and persistence of SARS-CoV-2 RNA in sewers. RNA concentrations were positively correlated between wastewater liquid and suspended solids, and between wastewater mixture and sewer biofilms. We identified two roles of biofilms in mediating the fate of SARS-CoV-2 RNA. Firstly, biofilms could affect RNA in-sewer stability. This impact could be limited in typical sewer systems with high COVID-19 prevalence, as estimated RNA loss was relatively small. However, in low-case settings, in-sewer RNA decay could affect detectability and precision of analysis, particularly over long hydraulic retention times before sample collection. The second role of biofilms is a reservoir for accumulating, retaining and distributing SARS-CoV-2 RNA under hydraulic changes, which could lead to prolonged virus presence and affect wastewater surveillance interpretation.

The proliferation of new psychoactive substances (NPS) over recent years has made their surveillance complex. The analysis of raw municipal influent wastewater can allow a broader insight into community consumption patterns of NPS. This study examines data from an international wastewater surveillance program that collected and analysed influent wastewater samples from up to 47 sites in 16 countries between 2019 and 2022. Influent wastewater samples were collected over the New Year period and analysed using validated liquid chromatog-raphy - mass spectrometry methods. Over the three years, a total of 18 NPS were found in at least one site. Synthetic cathinones were the most found class followed by phenethylamines and designer benzodiazepines. Furthermore, two ketamine analogues, one plant based NPS (mitragynine) and methiopropamine were also quantified across the three years. This work demonstrates that NPS are used across different continents and countries with the use of some more evident in particular regions. For example, mitragynine has highest mass loads in sites in the United States, while eutylone and 3-methylmethcathinone increased considerably in New Zealand and in several European countries, respectively. Moreover, 2F-deschloroketamine, an analogue of ke-tamine, has emerged more recently and could be quantified in several sites, including one in China, where it is considered as one of the drugs of most concern. Finally, some NPS were detected in specific regions during the initial sampling campaigns and spread to additional sites by the third campaign. Hence, wastewater surveillance can provide an insight into temporal and spatial trends of NPS use.

The influence of WWTP treatment standard on contaminant breakthrough is explored for 293 compounds.

BACKGROUND AND AIM: Per- and polyfluoroalkyl substances (PFAS) have been associated with altered kidney, thyroid, and cardiometabolic function markers, particularly elevated total cholesterol, but the evidence for specific health conditions has been inconclusive. We quantified the single and combined associations of PFAS on 17 biomarkers and 13 related health conditions in Australian communities with PFAS-contaminated water from the historical use of aqueous film-forming foam in firefighting activities. METHODS: This was a cross-sectional study of 881 adults in three exposed communities and 801 adults in three comparison communities. Participants self-reported their health and sociodemographic characteristics, and provided blood samples for measurement of nine PFAS and 17 biomarkers. We estimated differences in mean biomarker concentrations for each PFAS (PFOS, PFOA, and PFHxS) using linear regression and for the PFAS-mixture using Bayesian kernel machine regression. We also estimated prevalence ratios of biomarker concentrations above/below the reference limit and self-reported health conditions using modified Poisson regression. RESULTS: We observed higher mean total cholesterol and uric acid concentrations with higher single and mixture PFAS concentrations in blood serum, with varying certainty across communities and PFAS. PFOA was associated with higher prevalence of self-reported hypercholesterolemia (one community) and gout and kidney disease (two communities), but PFOS and PFHxS were associated with lower prevalence of gout and kidney disease. No clear associations were observed for self-reported cardiovascular disease, and there was less certainty for liver and thyroid function markers and disease due to low prevalence. CONCLUSIONS: Our study is one of few that simultaneously quantifies the associations of a PFAS-mixture on a large number of biomarkers and underlying health conditions in multiple communities. Our findings for total cholesterol and uric acid were consistent with previous studies; however, few associations were consistent across communities and the cross-sectional design limited causal inference. KEYWORDS: perfluoroalkyl substances, lipids, liver, kidney, thyroid

Transformation of biomarkers (or their stability) during sewer transport is an important issue for wastewater-based epidemiology (WBE). Most studies so far have been conducted in the laboratory, which usually employed unrealistic conditions. In the present study, we utilized a pilot sewer system including a gravity pipe and a rising main pipe to investigate the fate of 24 pharmaceutical biomarkers. A programmable logic controller was used to control and monitor the system including sewer operational conditions and wastewater properties. Sequential samples were collected that can represent hydraulic retention time (HRT) of up to 8 h in a rising main and 4 h in a gravity sewer. Wastewater parameters and biomarker concentrations were analysed to evaluate the stability and transformation kinetics. The wastewater parameters of the pilot system were close to the conditions of real sewers. The findings of biomarker transformation were also close to real sewer data with seventeen biomarkers reported as stable while buprenorphine, caffeine, ethyl-sulfate, methadone, paracetamol, paraxanthine and salicylic acid degraded to variable extents. Both zero-order and first-order kinetics were used to model the degradation of unstable biomarkers and interestingly the goodness of fit R2 for the zero-order model was higher than the first-order model for all unstable biomarkers in the rising main. The pilot sewer system simulates more realistic conditions than benchtop laboratory setups and may provide a more accurate approach for assessing the in-sewer transformation kinetics and stability of biomarkers.

Systematic sampling and analysis of wastewater samples are increasingly adopted for estimating drug consumption in communities. An understanding of the in-sewer transportation and transformation of illicit drug biomarkers is critical for reducing the uncertainty of this evidence-based estimation method. In this study, biomarkers stability was investigated in lab-scale sewer reactors with typical sewer conditions. Kinetic models using the Bayesian statistics method were developed to simulate biomarkers transformation in reactors. Furthermore, a field-scale study was conducted in a real pressure sewer pipe with the systematical spiking and sampling of biomarkers and flow tracers. In-sewer degradation was observed for some spiked biomarkers over typical hydraulic retention time (i.e., a few hours). Results indicated that sewer biofilms prominently influenced biomarker stability with the retention time in wastewater. The fits between the measured and the simulated biomarkers transformation demonstrated that the lab-based model could be extended to estimate the changes of biomarkers in real sewers. Results also suggested that the variabilities of biotransformation and analytical accuracy are the two major contributors to the overall estimation uncertainty. Built upon many previous lab-scale studies, this study is one critical step forward in realizing wastewater-based epidemiology by extending biomarker stability investigations from laboratory reactors to real sewers.

AllergyVolume 74, Issue 4 p. 812-815 LETTER TO THE EDITOR Cord-serum per- and poly-fluoroalkyl substances and atopy and eczema at 12-months Adrian J. Lowe, Corresponding Author Adrian J. Lowe lowea@unimelb.edu.au orcid.org/0000-0002-4691-8162 Allergy and Lung Health Unit, Melbourne School of Population and Global Health, University of Melbourne, Parkville, Victoria, Australia Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Victoria, Australia Correspondence Adrian Lowe, Allergy and Lung Health Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Carlton, VIC, Australia. Email: lowea@unimelb.edu.auSearch for more papers by this authorShyamali C. Dharmage, Shyamali C. Dharmage orcid.org/0000-0001-6063-1937 Allergy and Lung Health Unit, Melbourne School of Population and Global Health, University of Melbourne, Parkville, Victoria, Australia Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Victoria, AustraliaSearch for more papers by this authorMichael J. Abramson, Michael J. Abramson orcid.org/0000-0002-9954-0538 School of Public Health & Preventive Medicine, Monash University, Melbourne, Victoria, AustraliaSearch for more papers by this authorSoumini Vijayasarathy, Soumini Vijayasarathy orcid.org/0000-0002-0702-3470 Queensland Alliance for Environmental Health Sciences (QAEHS), The University of Queensland, Woolloongabba, Queensland, AustraliaSearch for more papers by this authorBircan Erbas, Bircan Erbas orcid.org/0000-0001-9597-418X School of Psychology and Public Health, La Trobe University, Bundoora, Victoria, AustraliaSearch for more papers by this authorJochen F. Mueller, Jochen F. Mueller orcid.org/0000-0002-0000-1973 Queensland Alliance for Environmental Health Sciences (QAEHS), The University of Queensland, Woolloongabba, Queensland, AustraliaSearch for more papers by this authorCaroline J. Lodge, Caroline J. Lodge orcid.org/0000-0002-2342-3888 Allergy and Lung Health Unit, Melbourne School of Population and Global Health, University of Melbourne, Parkville, Victoria, Australia Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Victoria, AustraliaSearch for more papers by this author Adrian J. Lowe, Corresponding Author Adrian J. Lowe lowea@unimelb.edu.au orcid.org/0000-0002-4691-8162 Allergy and Lung Health Unit, Melbourne School of Population and Global Health, University of Melbourne, Parkville, Victoria, Australia Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Victoria, Australia Correspondence Adrian Lowe, Allergy and Lung Health Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Carlton, VIC, Australia. Email: lowea@unimelb.edu.auSearch for more papers by this authorShyamali C. Dharmage, Shyamali C. Dharmage orcid.org/0000-0001-6063-1937 Allergy and Lung Health Unit, Melbourne School of Population and Global Health, University of Melbourne, Parkville, Victoria, Australia Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Victoria, AustraliaSearch for more papers by this authorMichael J. Abramson, Michael J. Abramson orcid.org/0000-0002-9954-0538 School of Public Health & Preventive Medicine, Monash University, Melbourne, Victoria, AustraliaSearch for more papers by this authorSoumini Vijayasarathy, Soumini Vijayasarathy orcid.org/0000-0002-0702-3470 Queensland Alliance for Environmental Health Sciences (QAEHS), The University of Queensland, Woolloongabba, Queensland, AustraliaSearch for more papers by this authorBircan Erbas, Bircan Erbas orcid.org/0000-0001-9597-418X School of Psychology and Public Health, La Trobe University, Bundoora, Victoria, AustraliaSearch for more papers by this authorJochen F. Mueller, Jochen F. Mueller orcid.org/0000-0002-0000-1973 Queensland Alliance for Environmental Health Sciences (QAEHS), The University of Queensland, Woolloongabba, Queensland, AustraliaSearch for more papers by this authorCaroline J. Lodge, Caroline J. Lodge orcid.org/0000-0002-2342-3888 Allergy and Lung Health Unit, Melbourne School of Population and Global Health, University of Melbourne, Parkville, Victoria, Australia Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Victoria, AustraliaSearch for more papers by this author First published: 14 November 2018 https://doi.org/10.1111/all.13669Citations: 2Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. 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The correction factor (CF) is a critical parameter for back estimating the consumption of a drug via wastewater-based epidemiology (WBE). The CF is usually the excretion factor (EF) of the drug or metabolite (the fraction of drug excreted after consumption and the molecular mass ratio of parent drug/metabolite) traditionally determined by human pharmacokinetic studies. An alternative approach to derive CFs is to compare the consumption data with the loads measured by WBE in representative wastewater samples. For this purpose, during the 2016 Australian Census week, more than 500 wastewater samples were collected from 83 wastewater treatment plants across Australia (covering >60% of the Australian population) and analyzed for codeine, methadone, and methadone metabolite, EDDP. National sales data for codeine and methadone to local pharmacies were obtained to estimate the CFs for the three biomarkers. The CFs estimated for codeine and EDDP in this study, 29% (95% CI = 28%-30%) and 50% (95% CI = 49%-52%), respectively, are significantly different from the EFs deduced from pharmacokinetic data (60% and 25%), while methadone's CF is relatively similar to previously used values (22% vs 27.5%). The newly derived CFs were applied to available data in the literature and produced better matches between estimates and consumption data than previously reported. It is thus suggested that the new approach be used to derive the CFs of other drugs of interest for WBE application when limited pharmacokinetic data are available.