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The antidiabetic drug Metformin (MET), one of the most prevalent pharmaceuticals in the environment, is currently detected in surface waters in the range of ng/L to low μg/L. As current knowledge regarding the long-term effects of environmentally relevant concentrations of MET in nontarget organisms is limited, the present study aimed at investigating the generational effects of MET, in concentrations ranging from 390 to 14 423 ng/L in the model organism

This article critically reviews analytical method validation and quality control applied to the environmental chemistry field. The review focuses on the determination of organic micropollutants (OMPs), specifically emerging contaminants and pesticides, in the aquatic environment. The analytical technique considered is (gas and liquid) chromatography coupled to mass spectrometry (MS), including high-resolution MS for wide-scope screening purposes. An analysis of current research practices outlined in the literature has been performed, and key issues and analytical challenges are identified and critically discussed. It is worth emphasizing the lack of specific guidelines applied to environmental analytical chemistry and the minimal regulation of OMPs in waters, which greatly affect method development and performance, requirements for method validation, and the subsequent application to samples. Finally, a proposal is made for method validation and data reporting, which can be understood as starting points for further discussion with specialists in environmental analytical chemistry. Expected final online publication date for the Annual Review of Analytical Chemistry, Volume 16 is June 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

This work investigated, during one year, the occurrence and fate of 52 contaminants of emerging concern (CECs) in transnational river basins and coastal areas of the North of Portugal and Galicia (NW Spain) and the wastewater treatment plants (WWTPs) discharging on these environments. The different CECs investigated included pharmaceuticals, personal care products, industrial chemicals, among others, of which ca. 90 % would fulfill the persistence, mobility and toxicity criteria proposed by the German Environmental Agency. The results showed the ubiquitous presence of these CECs and an incomplete removal of over 60 % of them with current conventional WWTPs. These findings highlight the requirement of a prominent and coordinated upgrade of WWTP treatments in order to meet the future European Union regulations on urban wastewater treatment and surface water quality. In fact, even some compounds exhibiting high removals, such as caffeine or xylene sulfonate, were frequently detected in river and estuarine waters at the high ng L−1 level. Thus, our preliminary risk assessment study concluded that 18 of the CECs presented a potential risk for the environment, being caffeine, sulpiride, perfluorooctanoic acid (PFOA), diclofenac, fipronil and perfluorobutanoic acid (PFBA) the most concerning ones. Yet, additional toxicity data as well as a more robust information on persistence and mobility of CECs are necessary for better estimating the magnitude of the problem and improve risk assessment. As an example, in the case of the antidiabetic metformin, recent research has revealed toxicity for model fish species at concentration levels below those found in 40 % of the river water samples analyzed in this work This work was financed by the European Regional Development Fund through the Interreg V-A Spain-Portugal Programme (POCTEP) 2014-2020 (ref. 0725_NOR_WATER_1_P), the Agencia Estatal de Investigación MCIN/AEI/10.13039/501100011033 (ref. PID2020-117686RB-C32) and the Consellería de Cultura, Educación y Universidades da Xunta de Galicia (ref. ED431C 2021/06). The study was also supported by the Portuguese Foundation for Science and Technology (FCT) under the projects [UIDB/04423/2020 and UIDP/04423/2020]. R.M. acknowledges Banco Santander and Universidade de Santiago de Compostela for her outstanding researcher contract, N. A. acknowledges the FCT for his Ph.D. grant DFA/BD/6218/2020 and T.N. acknowledges FCT Individual Call to Scientific Employment Stimulus 2022 (2022.02925.CEECIND). The authors also want to acknowledge Agilent Technologies for providing the equipment described in Section 2.4 and the different entities which have collaborated in the sampling campaign: VIAQUA, Augas de Galicia, Confederación Hidrográfica do Miño-Sil, Águas do Porto, Efacec and Águas do Norte SI

This work presents an optimized gas chromatography–electron ionization–high-resolution mass spectrometry (GC-EI-HRMS) screening method. Different method parameters affecting data processing with the Agilent Unknowns Analysis SureMass deconvolution software were optimized in order to achieve the best compromise between false positives and false negatives. To this end, an accurate-mass library of 26 model compounds was created. Then, five replicates of mussel extracts were spiked with a mixture of these 26 compounds at two concentration levels (10 and 100 ng/g dry weight in mussel, 50 and 500 ng/mL in extract) and injected in the GC-EI-HRMS system. The results of these experiments showed that accurate mass tolerance and pure weight factor (combination of reverse-forward library search) are the most critical factors. The validation of the developed method afforded screening detection limits in the 2.5–5 ng range for passive sampler extracts and 1–2 ng/g for mussel sample extracts, and limits of quantification in the 0.6–3.2 ng and 0.1–1.8 ng/g range, for the same type of samples, respectively, for 17 model analytes. Once the method was optimized, an accurate-mass HRMS library, containing retention indexes, with ca. 355 spectra of derivatized and non-derivatized compounds was generated. This library (freely available at https://doi.org/10.5281/zenodo.5647960), together with a modified Agilent Pesticides Library of over 800 compounds, was applied to the screening of passive samplers, both of polydimethylsiloxane and polar chemical integrative samplers (POCIS), and mussel samples collected in Galicia (NW Spain), where a total of 75 chemicals could be identified Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This research was funded by Xunta de Galicia (ED431C 2021/06 and V.C. predoctoral contract: ED481A-2017/156), the Spanish Agencia Estatal de Investigación—MCIN/AEI/10.13039/501100011033 (ref. CTM2017-84763-C3-R-2 and PID2020-117686RB-C32), and FEDER/ERDF funds SI

The COVID-19 pandemic spread rapidly worldwide in the year 2020, which was initially restrained by drastic mobility restrictions. In this work, we investigated the use of illicit drugs (amphetamine, methamphetamine, ecstasy, cocaine and cannabis), and licit substances of abuse (alcohol and tobacco) during the earlier months (March–July 2020) of the pandemic restrictions in four Spanish (Bilbao and its metropolitan area, Vitoria-Gasteiz, Castellón and Santiago de Compostela) and two Portuguese (Porto and Vila do Conde) locations by wastewater-based epidemiology (WBE). The results show that no methamphetamine was detected in any of the locations monitored, while amphetamine use was only detectable in the two locations from the Basque Country (Bilbao and its metropolitan area and Vitoria-Gasteiz), with high estimated average usage rates (700–930 mg day−1 1000 inhabitant−1). The remaining substances were detected in all the investigated catchment areas. In general, no remarkable changes were found in population normalized loads compared to former years, except for cocaine (i.e. its main metabolite, benzoylecgonine). For this drug, a notable decrease in use was discernible in Castellón, while its usage in Porto and Santiago de Compostela seemed to continue in a rising trend, already initiated in former years. Furthermore, two events of ecstasy (3,4-methylenedioxymethamphetamine, MDMA) dumping in the sewage network were confirmed by enantiomeric analysis, one in Santiago de Compostela just prior the lockdown and the second one in the Bilbao and its metropolitan area in July after relieving the more stringent measures. The latter could also be associated with a police intervention. The comparison of WBE with (web) survey data, which do not provide information at a local level, points towards contradictory conclusions for some of the substances, thereby highlighting the need for stable WBE networks capable of near real-time monitoring drug use This research was funded by the Spanish Agencia Estatal de Investigación – MCIN/AEI/10.13039/501100011033 (CTM2016-81935-REDT, PID2020-117686RB-C32 and PID2020-117686RB-C31), Consellería de Cultura de Galicia, Educación e Universidades (ED481A-2020/258 and ED431C 2021/06), Delegación del Gobierno para el Plan Nacional Sobre Drogas (2020I009), Instituto de Salud Carlos III-Next Generation EU (RD21/0009/0012 – RIAPAd Network), Generalitat Valenciana (Research Group of Excellence Prometeo 2019/040), Fundación Vital (Vitoria-Gasteiz) and Ayuntamiento de Vitoria-Gasteiz SI

Metformin (MET), an anti-diabetic pharmaceutical of large-scale consumption, is increasingly detected in surface waters. However, current knowledge on the long-term effects of MET on non-target organisms is limited. The present study aimed to investigate the effects of MET in the model freshwater teleost Danio rerio, following a full life-cycle exposure to environmentally relevant concentrations (390 to 14 423 ng/L). Considering that the mode of action (MoA) of MET on non-target organisms remains underexplored and that MET may act through similar human pathways, i.e., lipid and energy metabolisms, biochemical markers were used to determine cholesterol and triglycerides levels, as well as mitochondrial complex I activity in zebrafish liver. Also, the hepatosomatic index as an indication of metabolic disruption, and the expression levels of genes involved in MET's putative MoA, i.e. acaca, acadm, cox5aa, idh3a, hmgcra, prkaa1, were determined, the last by qRT-PCR. A screening of mRNA transcripts, associated with lipid and energy metabolisms, and other signaling pathways potentially involved in MET-induced toxicity were also assessed using an exploratory RNA-seq analysis. The findings here reported indicate that MET significantly disrupted critical biochemical and molecular processes involved in zebrafish metabolism, such as cholesterol and fatty acid biosynthesis, mitochondrial electron transport chain and tricarboxylic acid cycle, concomitantly to changes on the hepatosomatic index. Likewise, MET impacted other relevant pathways mainly associated with cell cycle, DNA repair and steroid hormone biosynthesis, here reported for the first time in a non-target aquatic organism. Non-monotonic dose response curves were frequently detected in biochemical and qRT-PCR data, with higher effects observed at 390 and 2 929 ng/L MET treatments. Collectively, the results suggest that environmentally relevant concentrations of MET severely disrupt D. rerio metabolism and other important biological processes, supporting the need to revise the proposed environmental quality standard (EQS) and predicted no-effect concentration (PNEC) for MET This study was developed under the project Nor-Water – Pollutants of emerging concern in watersheds from Galicia-northern Portugal: new tools for risk management [Reference: 0725_NOR_WATER_1_P], financed by Programa de Cooperação Interreg Portugal/Espanha, (POCTEP) 2014–2020. The study was also supported by the National Funds through Portuguese Foundation for Science and Technology (FCT) under the projects [UIDB/04423/2020, UIDP/04423/2020, UIDB/04033/2020 and LA/P/0126/2020]. S. Barros, M. Pinheiro, H. Morais and N. Alves acknowledge FCT for their Ph.D. grants PD/BD/143090/2018; SFRH/BD/147834/2019; SFRH/BD/139762/2018 and DFA/BD/6218/2020, respectively. Financial support by Xunta de Galicia (ED431C 2021/06) and the Agencia Estatal de Investigación (España) - MCIN/AEI/ 10.13039/501100011033 (PID2020–117686RB-C32) is also gratefully acknowledged. 2024-07-14 SI

Metformin (MET) is an anti-diabetic pharmaceutical with a large-scale consumption, which is increasingly detected in surface waters. However, current knowledge on the generational effects of MET exposure in the metabolism of non-target organisms is limited. The present study aimed at investigating the effects of MET in the model freshwater teleost Danio rerio, following a generational exposure (from egg up to 9 months exposure) to environmentally relevant concentrations ranging from 361 ng/L to 13 000 ng/L. Biochemical markers were used to determine cholesterol and triglycerides levels, as well as mitochondrial complex I activity in males and females zebrafish liver. mRNA transcript changes were also assessed in the liver of both sexes by means of an exploratory RNA-seq analysis and expression levels of key genes involved in the energy metabolism and lipid homeostasis, i.e. acaca, acadm, cox5aa, idh3a, hmgcra, prkaa1, were determined using qRT-PCR analysis. The findings here reported revealed that MET was able to significantly disrupt critical biochemical and molecular processes involved in zebrafish metabolism, such as cholesterol and fatty acid biosynthesis, the mitochondrial electron transport chain and the tricarboxylic acid cycle, concomitantly to changes on the hepatosomatic index. Non-monotonic dose response curves were frequently detected in the gene expression profile, with higher effects observed for 361 ng/L and 2 166 ng/L concentrations. Collectively, the obtained results suggest that environmentally relevant concentrations of MET are able to severely disrupt D. rerio metabolism, with potential impacts at the ecological level, supporting the need to update the environmental quality standard (EQS) and predicted no-effect concentration (PNEC) for MET.Graphical abstractHighlightsDanio rerio was exposed to metformin for a full generation;MET affected COX I activity, as well as Chol and TGL content in zebrafish liver;MET altered mRNA levels of genes involved in energy metabolism and lipid content;Non-monotonic dose-response curves were frequently detected;Due to the results obtained, MET PNEC should be reviewed.

The bioaccumulation and depuration of seven organophosphorus flame retardants (OPFRs) in marine mussel Mytilus galloprovincialis were studied. OPFRs showed to be bioavailable in aquatic environments. When mussels are exposed to environmentally relevant concentrations of OPFRs, uptake kinetics fit well to a first-order model with a single compartment; in contrast depuration rates were generally underestimated by that model, most likely because it does not take into account the biotransformation of OPFRs by the organisms. The highest bioaccumulation rates were observed for tricresyl phosphate (TCrP), triphenyl phosphate (TPhP) and 2-ethylhexyldiphenylphosphate (EHDPP). This could be due to the presence of aryl groups in these compounds, their low solubility in water, and their affinity for fat tissues. According to these findings TCrP, with a BCF value of 4042 L kg−1 wet weight, should be classified in environmental regulations as an accumulative chemical This research was supported by the Spanish Government through research project BIOPLAS (PID2019-108857RB-C32), the Spanish Agencia Estatal de Investigación (ref. CTM2017-84763-C3-R-2), Xunta de Galicia (ED431C2017/36 and Verónica Castro predoctoral contract, ref.: ED481A-2017/156) and FEDER/ERDF funds. This work has received financial support from the Xunta de Galicia (Centro de investigación de Galicia accreditation 2019-2022) and the European Union (European Regional Development Fund - ERDF) 2023-09-17 SI

Wastewater-based epidemiology is an additional indicator of drug use that is gaining reliability to complement the current established panel of indicators. The aims of this study were to: (i) assess spatial and temporal trends of population-normalized mass loads of benzoylecgonine, amphetamine, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) in raw wastewater over 7 years (2011-17); (ii) address overall drug use by estimating the average number of combined doses consumed per day in each city; and (iii) compare these with existing prevalence and seizure data.Analysis of daily raw wastewater composite samples collected over 1 week per year from 2011 to 2017.Catchment areas of 143 wastewater treatment plants in 120 cities in 37 countries.Parent substances (amphetamine, methamphetamine and MDMA) and the metabolites of cocaine (benzoylecgonine) and of ΔBenzoylecgonine was the stimulant metabolite detected at higher loads in southern and western Europe, and amphetamine, MDMA and methamphetamine in East and North-Central Europe. In other continents, methamphetamine showed the highest levels in the United States and Australia and benzoylecgonine in South America. During the reporting period, benzoylecgonine loads increased in general across Europe, amphetamine and methamphetamine levels fluctuated and MDMA underwent an intermittent upsurge.The analysis of wastewater to quantify drug loads provides near real-time drug use estimates that globally correspond to prevalence and seizure data.

Global production of synthetic polymers, led by polyethylene (PE), rose steadily in the last decades, and marine ecosystems are considered as a global sink. Although PE is not biodegradable, in coastal areas it fragments into microplastics (MP) readily taken up by biota, and have been postulated as vectors of hydrophobic chemicals to marine organisms. We have tested this hypothesis using two organisms representative of the marine plankton, the holoplanktonic copepod Acartia clausi, and the meroplanktonic larva of the Paracentrotus lividus sea-urchin, and two model chemicals with similar hydrophobic properties, the 4-n-Nonylphenol and the 4-Methylbenzylidene-camphor used as plastic additive and UV filter in cosmetics. Both test species actively ingested the MP particles. However, the presence of MP never increased the bioaccumulation of neither model chemicals, nor their toxicity to the exposed organisms. Bioaccumulation was a linear function of waterborne chemical disregarding the level of MP. Toxicity, assessed by the threshold (EC10) and median (EC50) effect levels, was either independent of the level of MP or even in some instances significantly decreased in the presence of MPs. These consistent results challenge the assumption that MP act as vectors of hydrophobic chemicals to planktonic marine organisms This study has received funding by the Spanish Government (MINECO/AEI) through Projects PCIN-2015-187-C03-03 (JPI Oceans EPHEMARE), PCIN-2015-170-C02-01 (JPI Oceans BASEMAN), CTM2016-77945-C3, and CTM2017-84763-C3-2-R, by Xunta de Galicia through “Program of Consolidation and structuring of competitive research groups in the University system of Galicia” (Refs GRC2013-004, ED431C 2017/28 and ED431C 2017/36), and by the European Union through the European Regional Development Fund (ERDF). N. S.-G. was granted with a postdoctoral fellowship Mod. A (2016) by Axencia Galega de Innovación (GAIN), Xunta de Galicia SI

The analysis of wastewater for the determination of human biomarkers of exposure (human metabolites) is a non-intrusive, economic and complementary alternative to the analysis of urine in the monitoring of human exposure to chemicals of concern. This study provides the first gas chromatography-based method for the determination of three metabolites of chlorinated organophosphorous flame retardants (OPFRs: bis(2-chloroethyl) phosphate, bis(chloropropyl) phosphate and bis(1,3-dichloro-2-propyl) phosphate) in wastewater. A solid-phase extraction procedure based on the use of mixed-mode reversed-phase weak anion exchange sorbents was optimized including a fractionated elution of OPFRs and their metabolites. Analytes derivatization was investigated by comparing two silylating reagents, N-tert-butyldimethylsilyl-N-methyltrifluoroacetamide and N-methyl-N-(trimethylsilyl)trifluoroacetamide, the first one providing better results. Determination was performed by gas chromatography-high resolution mass spectrometry with a quadrupole-time-of-flight system (GC-QTOF) in order to improve selectivity. Furthermore, the use of GC-QTOF combined with the specific ion obtained from silylated metabolites (m/z 154.9924) can be exploited to screen for other phosphate ester metabolites. Under final conditions, the overall method performance was satisfactory, affording method detection limits ranging from 1.1 to 4.6 ng/L, percentages of recovery from 90% to 110%, and relative standard deviations below 13%. The analysis of composite raw wastewater samples collected over 24 h in the NW of Spain allowed to quantify, for the first time in this matrix, the metabolite bis(chloropropyl) phosphate at levels over 60 ng/L This work was financially supported by the Spanish Agencia Estatal de Investigación (project no. CTM2017-84763-C3-2-R), the Galician Council of Culture, Education and Universities (ED431C2017/36, VC predoctoral contract, ED481A-2017/156, and IGM postdoctoral contract, Plan Galego I2C-Modalidade B, ED481D 2017/003), Gil Dávila Foundation (VC research grant) and FEDER/ERDF SI

This is the Author’s Accepted Manuscript of the following article: Schulze, S., Zahn, D., Montes, R., Rodil, R., Quintana, J., & Knepper, T. et al. (2019). Occurrence of emerging persistent and mobile organic contaminants in European water samples. Water Research, 153, 80-90. doi: 10.1016/j.watres.2019.01.008 The release of persistent and mobile organic chemicals (PMOCs) into the aquatic environment puts the quality of water resources at risk. PMOCs are challenging to analyze in water samples, due to their high polarity. The aim of this study was to develop novel analytical methods for PMOCs and to investigate their occurrence in surface and groundwater samples. The target compounds were culled from a prioritized list of industrial chemicals that were modeled to be persistent, mobile, and emitted into the environment. Analytical screening methods based on mixed-mode liquid chromatography (LC), hydrophilic interaction LC, reversed phase LC, or supercritical fluid chromatography in combination with mass spectrometric detection were successfully developed for 57 target PMOCs and applied to 14 water samples from three European countries. A total of 43 PMOCs were detected in at least one sample, among them 23 PMOCs that have not been reported before to occur in environmental waters. The most prevalent of these novel PMOCs were methyl sulfate, 2-acrylamino-2-methylpropane sulfonate, benzyltrimethylammonium, benzyldimethylamine, trifluoromethanesulfonic acid, 6-methyl-1,3,5-triazine-diamine, and 1,3-di-o-tolylguanidine occurring in ≥50% of the samples at estimated concentrations in the low ng L−1 up to μg L−1 range. The approach of focused prioritization combined with sensitive target chemical analysis proved to be highly efficient in revealing a large suite of novel as well as scarcely investigated PMOCs in surface and groundwater This work has been funded by the German BMBF (02WU1347A/B) and the Spanish MINECO/AEI (JPIW2013-117) in the frame of the collaborative international consortium (WATERJPI2013 – PROMOTE) of the Water Challenges for a Changing World Joint Programming Initiative (Water JPI) Pilot Call. RM, RR and JBQ also acknowledge Galician Council of Culture, Education and Universities and FEDER/EDRF funding (ED431C2017/36) SI

The presence of persistent and mobile organic contaminants (PMOC) in aquatic environments has become a matter of concern due to their ability of breaking through natural and anthropogenic barriers, even reaching drinking water. The presence of many of these compounds in surface and drinking water has been reported in screening studies, but there is still a lack of analytical methods capable of quantifying them. Herein, we propose a method combining mixed-mode-solid-phase extraction (MM-SPE) as preconcentration technique and mixed-mode liquid chromatography (MMLC) coupled to tandem mass spectrometry as a determination technique for the quantitative determination of 23 target PMOCs in surface and drinking water samples. When compared to reversed-phase liquid chromatography, the MMLC protocol has proven to be superior in both retentive capabilities and peak shape for ionic compounds, while performing also well for neutrals. The overall method performance was satisfactory with limits of quantification under 50 ng L–1 for most of analytes in both surface and drinking water. The relative standard deviation was lower than 20%, and the average recovery was 78 and 80% in surface and drinking water, respectively. The method was applied to 15 water samples collected in Spain, where 17 out of the 23 target PMOCs were quantified in at least one sample. Among them, 6 chemicals (e.g., benzyltrimethylammonium) are reported and/or quantified here for the first time This work has been funded by the Spanish MINECO/AEI (JPIW2013-117, CTM2014-56628-C3-2-R, and CTM2017-84763-C3-2-R) in the frame of the collaborative international consortium (WATERJPI2013 – PROMOTE) of the Water Challenges for a Changing World Joint Programming Initiative (Water JPI) Pilot Call, the Galician Council of Culture, Education and Universities (ED431C2017/36) and FEDER/EDRF funding SI

info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-117686RB-C33/ES/PLATAFORMAS ANALITICAS FLUIDICAS PARA EVALUAR LA EXPOSICION HUMANA Y AMBIENTAL A CONTAMINANTES EMERGENTES Notwithstanding the fact that microplastic fragments were encountered in the human stool, little effort has been geared towards elucidating the impact of chemical additives upon the human health. In this work, standardized bioaccessibility tests under both fasting and fed conditions are herein applied to the investigation of human oral bioaccessibility of plastic additives and monomers (i.e. eight phthalate esters (PAEs) and bisphenol A (BPA)) in low-density polyethylene (LDPE) and polyvinyl chloride (PVC) microplastics. The generation of phthalate monoesters is evaluated in the time course of the bioaccessibility tests. Maximum gastric and gastrointestinal bioaccessibility fractions are obtained for dimethyl phthalate, diethyl phthalate and BPA, within the range of 55–83%, 40–68% and 37–67%, respectively, increasing to 56–92% and 41–70% for dimethyl phthalate and diethyl phthalate, respectively, whenever their hydrolysis products are considered. Bioaccessibility fractions of polar PAEs are dependent upon the physicochemical characteristics of the microplastics, with greater bioaccessibility for the rubbery polymer (LDPE). With the method herein proposed, oral bioaccessible pools of moderately to non-polar PAEs can be also accurately assessed for risk-assessment explorations, with values ranging from 1.8% to 32.2%, with again significantly larger desorption percentages for LDPE. Our results suggested that the highest gastric/gastrointestinal bioaccessibility of the eight PAEs and BPA is reached under fed-state gastrointestinal extraction conditions because of the larger amounts of surface-active biomolecules. Even including the bioaccessibility factor within human risk assessment/exposure studies to microplastics, concentrations of dimethyl phthalate, di-n-butyl phthalate and BPA exceeding 0.3% (w/w) may pose severe risks after oral uptake in contrast to the more hydrophobic congeners for which concentrations above 3% (w/w), except for diethylhexyl phthalate, would be tolerated The authors acknowledge the financial support provided by the Spanish Ministry of Science and Innovation (MCIN) and Spanish State Research Agency (AEI/10.13039/501100011033) through the projects CTM2017-84763-C3-2-R, CTM2017-84763-C3-3-R, CTM2017-90890-REDT, PID2020-117686RB-C32 and PID2020-117686RB-C33, by the “ERDF-A way of making Europe”, by the Galician Government (Consellería de Economía e Industria, Xunta de Galicia, ref. ED431C 2021/06) and by La Caixa–Fundación CajaCanarias for MJT-R contract. We would like to express our gratitude to Restek (kind gift of the Biphenyl column). The technical support on SEM images by Dr. Ferran Hierro from the Scientific and Technological Centre at the UIB is greatly acknowledged SI

Amphetamine (AMP), methamphetamine (MAMP) and 3,4-methylenedioxymethamphetamine (MDMA) occur in wastewater not only as a result of illicit consumption, but also, in some cases, from prescription drug use or by direct drug disposal into the sewage system. Enantiomeric profiling of these chiral drugs could give more insight into the origin of their occurrence. In this manuscript, a new analytical methodology for the enantiomeric analysis of amphetamine-like substances in wastewater has been developed. The method consists of a solid-phase extraction (SPE) followed by liquid chromatography-triple quadrupole-tandem mass spectrometry (LC-MS/MS), which showed low quantification limits in the 2.4–5.5 ng L−1 range. The LC-MS/MS method was first applied to characterize a total of 38 solid street drug samples anonymously provided by consumers. The results of these analysis showed that AMP and MDMA trafficked into Spain are synthesized as racemate, while MAMP is exclusively produced as the S(+)-enantiomer. Then, the analytical method was employed to analyse urban wastewater samples collected from the wastewater treatment plants (WWTPs) of five different cities in 2018 and 2019. Consumption estimated through normalized population loads in wastewater showed an increased pattern of AMP use in the Basque Country. Furthermore, the enantiomeric profiling of wastewater samples was contrasted to lisdexamfetamine (LIS) and selegiline (SEL) prescription figures, two pharmaceuticals which metabolize to S(+)-AMP, and to R(-)-AMP and R(-)-MAMP, respectively. From this analysis, and considering uncertainties derived from metabolism and adherence to treatment, it was concluded that LIS is a relevant source of AMP in those cases with low wastewater loads, i.e. up to a maximum of 60% of AMP detected in wastewater in some samples could originate from LIS prescription, while SEL does not represent a significant source of AMP nor MAMP. Finally, removal efficiencies could be evaluated for the WWTP (serving ca. 860,000 inhabitants) with higher AMP influent concentrations. The removal of AMP was satisfactory with rates higher than 99%, whereas MDMA showed an average removal of approximately 60%, accompanied by an enrichment of R(-)-MDMA This study was supported by MINECO/MICINN/AEI projects (CTM2016-81935-REDT, CTM2017-84763-C3-2-R, CTM2017-84763-C3-1-R, CTM2017-84763-C3-3-R, PID2020-117686RB-C32, PID2020-117686RB-C31, PID2020-117686RB-C33), Galician Council of Culture, Education and Universities (ED481D-2017/003, ED431C-2017/36, ED481A-2020/258 and ED431C 2021/06), cofounded by FEDER/ERDF. UJI authors acknowledge the financial support of Generalitat Valenciana (Excellence Research Group, Prometeo 2019/040). Alberto Celma acknowledges the Spanish Ministry of Economy and Competitiveness for his predoctoral Grant (BES-2016-076914). Vanessa Gutmann acknowledges the support of the ERASMUS+ program. SI

Plasticizers are chemical compounds used in the production of flexible plastics for a large variety of applications. They are present in most of the environments and, hence, we are highly exposed to them via several routes (ingestion, inhalation, etc). Due to the endocrine disruption potential of some of these chemicals and the unknown toxicological effects of their alternatives, assessing human exposure to these contaminants is an issue of emerging concern. Herein we propose an analytical methodology for the determination of several plasticizer metabolites in wastewater as a non-invasive, cheap, and fast exposure monitoring tool complementary to the analysis of urine. A solid-phase extraction procedure followed by an ultra(high)-performance liquid chromatography-tandem mass spectrometry method was optimized and validated for 21 analytes among phthalate, terephthalate, and di-iso-nonyl cyclohexane-1,2-dicarboxylate metabolites. Method quantification limits ranged from 0.079 to 4.4 ng L−1. The method was applied to the analysis of seven daily composite wastewater samples collected in the NW of Spain. Metabolites of low molecular weight phthalates and of di-2-ethylhexyl phthalate were quantified in all samples, despite the existing regulations limiting the use of phthalates. Metabolites of terephthalates, introduced at the end of the 20th century as phthalate substituents, were also quantified in all samples, being the first time that they were detected in this matrix. Exposure back-calculation highlighted di-2-ethylhexyl terephthalate as the second most common plastic additive after diethyl phthalate in the population considered, reflecting the increasing substitution of di-2-ethylhexyl phthalate by its analogous terephthalate This work was financially supported by Agencia Estatal de Investigación, Spain (project no. CTM2017-84763-C3-2-R), Galician Council of Culture, Education and Universities, Spain (IGM postdoctoral contract, Plan Galego I2C-Modalidade B, grant no. ED481D-2017/003, AED predoctoral contract, grant no. ED481A-2020/258, and project no. ED431C-2017/36), Gil Dávila Foundation (AED research grant), and FEDER/ERDF 2022-11-26 SI

Data obtained from wastewater analysis can provide rapid and complementary insights in illicit drug consumption at community level. Within Europe, Spain is an important country of transit of both cocaine and cannabis. The quantity of seized drugs and prevalence of their use rank Spain at the top of Europe. Hence, the implementation of a wastewater monitoring program at national level would help to get better understanding of spatial differences and trends in use of illicit drugs. In this study, a national wastewater campaign was performed for the first time to get more insight on the consumption of illicit drugs within Spain. The 13 Spanish cities monitored cover approximately 6 million inhabitants (12.8% of the Spanish population). Untreated wastewater samples were analyzed for urinary biomarkers of amphetamine, methamphetamine, MDMA, cocaine, and cannabis. In addition, weekend samples were monitored for 17 new psychoactive substances. Cannabis and cocaine are the most consumed drugs in Spain, but geographical variations showed, for instance, comparatively higher levels of methamphetamine in Barcelona and amphetamine in Bilbao, with about 1-fold higher consumption of these two substances in such metropolitan areas. For amphetamine, an enantiomeric profiling was performed in order to assure the results were due to consumption and not to illegal dumping of production residues. Furthermore, different correction factors for the excretion of cannabis were used to compare consumption estimations. All wastewater results were compared with previously reported data, national seizure data and general population survey data, were a reasonable agreement was found. Daily and yearly drug consumption were extrapolated to the entire Spanish population with due precautions because of the uncertainty associated. These data was further used to estimate the retail drug market, where for instance cocaine illicit consumption alone was calculated to contribute to 0.2–0.5% of the Spanish gross domestic product (ca. 3000–6000 million Euro/year)., This study was supported by MINECO/AEI projects (CTM2016-81935-REDT, CTM2017-84763-C3-2-R, CTM2017-84763-C3-1-R, CTM2017-84763-C3-3-R, RTI2018-097158-B-C31 and CTM2017-90890-REDT), MICINN project (CEX2018-000794-S), Galician Council of Culture, Education and Universities (ED481D-2017/003, ED431C-2017/36 and ED481A-2020/258), cofounded by FEDER/ERDF. The UJI and CIDE (CSIC-UV-GV) authors acknowledge the financial support of Generalitat Valenciana (Excellence Research Group, Prometeo 2019/040 and Prometeo 2018/150, respectively). IDAEA-CSIC authors acknowledge the financial support of Generalitat de Catalunya (Exp. Num. SA-2018-780 and Consolidated Research Group 2017 SGR 01404) and the Spanish Ministry of Science and Innovation (Project CEX2018-000794-S). Alberto Celma acknowledges the Spanish Ministry of Economy and Competitiveness for his predoctoral Grant (BES-2016-076914). Elena Pitarch acknowledge the financial support of University Jaume I of Castellón, Spain (project UJI-B2018-55). Andreu Rico is supported by a postdoctoral grant provided by the Spanish Ministry of Science, Innovation and University (IJCI–2017–33465).

Phthalates are widely used plasticizers that produce endocrine-disrupting disorders. Quantifying exposure is crucial to perform risk assessments and to develop proper health measures. Herein, a wastewater-based epidemiology approach has been applied to estimate human exposure to six of the mostly used phthalates within the Spanish population. Wastewater samples were collected over four weekdays from seventeen wastewater treatment plants serving thirteen cities and ca. 6 million people (12.8 % of the Spanish population). Phthalate metabolite loads in wastewater were transformed into metabolite concentrations in urine and into daily exposure levels to the parent phthalates. Considering all the sampled sites, population-weighted overall means of the estimated concentrations in urine varied between 0.7 ng/mL and 520 ng/mL. Very high levels, compared to human biomonitoring data, were estimated for monomethyl phthalate, metabolite of dimethyl phthalate. This, together with literature data pointing to other sources of this metabolite in sewage led to its exclusion for exposure assessments. For the remaining metabolites, estimated concentrations were closer to those found in urine. Their 4-days average exposure levels ranged from 2 to 1347 μg/(day∙inh), exceeding in some sites the daily exposure thresholds set for di-i-butyl phthalate and di-n-buthyl phthalate by the European Food Safety Authority., Financial support. This study was supported by MCIU/AEI (projects CTM2016-81935-REDT, CTM2017-84763-C3-1-R, CTM2017-84763-C3-2-R, CTM2017-84763-C3-3-R, and CEX2018-000794-S), Galician Council of Culture, Education and Universities (ED481D 2017/003 and ED431C2017/36), Generalitat Valenciana (projects Prometeo/2018/155 and Prometeo/2019/040) and Universitat Jaume I (project UJI-B2018-55). Several of the above mentioned projects are cofunded by FEDER/ERDF. Sampling, sample and data provision and/or analytical support: Viaqua and Concello de Santiago de Compostela, EMAYA (Palma), Jordi Palatsi from Aqualia (Lleida WWTP), Cristian Mesa and Angela Vidal from Aigues de Barcelona (Barcelona WWTP), Iñigo González (Consorcio de Aguas de Bilbao-Bizkaia), the Public Entity of Wastewater Treatment (EPSAR) of the Generalitat Valenciana and especially Fernando Llavador. Luis Aceiton, Enrique Albors, Angel Jiménez, Maria José Tarrega, Sonia Tristante and all the personal of the WWTPs (Aguas de Valencia, Spain), are acknowledged for their help with the sampling. Sociedad de Fomento Agrícola Castellonense (FACSA, Castellon), and especially WWTP operators Santiago Querol and Sara Gargallo are acknowledged for providing wastewater samples from Castellón, as well as Subdirección General de Gestión del Agua, Ayuntamiento de Madrid, for allowing the collection of samples from Madrid centro.

This work provides a screening of organic contaminants and characterization of the dissolved organic matter in the sewer network until the municipal wastewater treatment plant (WWTP), identifying the network areas with a higher degree of contamination and their impact on the WWTP performance, particularly in the activated sludge reactor. Three monitoring campaigns were carried out at six selected locations of the sewage system (PVZ-1, PVZ-2, PS-F, PS-VC, CP-VC, and PS-T), influent (WWTPINF) and effluent (WWTPEFF) of the WWTP. Advanced analytical techniques were employed, namely excitation/emission matrix fluorescence-parallel factor analysis (EEM-PARAFAC), size exclusion chromatography with organic carbon detector (SEC-OCD), and liquid chromatography with high-resolution-mass spectrometric detection (LC-HRMS). EEM-PARAFAC showed higher fluorescence intensity for the protein-like component (C2), particularly at CP-VC (near seafood industries) associated with the presence of surfactants (~50 mg/L). SEC-OCD highlighted the WWTP efficiency in removing low molecular weight acids and neutrals. LC-HRMS tentatively identified 108 compounds of emerging concern (CEC) and similar detection patterns were obtained for all wastewater samples, except for PVZ-2 (lower detection), many of which occurred in the effluent. Eight CECs included on relevant Watch-Lists were detected in all WWTPEFF samples. Furthermore, 111 surfactants were detected, the classes more frequently found being alcohol ethoxylates (AEOs), nonylphenol polyethoxylates (NPEOs) and linear alkylbenzene sulphonates (LAS). The continuous presence of LAS and NPEOs allied to surfactants concentrations in the WWTPINF of 15–20 mg/L, with CP-VC location (linked with food industries) as an important contributor, explain the morphological changes in the activated sludge and high LAS content in the dewatered sludge, which may have impacted WWTP performance. i) Base-UIDB/50020/2020 and Programmatic-UIDP/50020/2020 Funding of LSRE-LCM, funded by national funds through FCT/MCTES (PIDDAC); ii) European Regional Development Fund through the Interreg V-A Spain-Portugal Programme (POCTEP) 2014–2020 (ref. 0725_NOR_WATER_1_P); iii) Xunta de Galicia (Verónica Castro predoctoral contract: ED481A-2017/156, and ED431C2017/36), the Spanish Agencia Estatal de Investigación – MCIN/AEI/ 10.13039/501100011033 (ref. PID2020-117686RB-C32); iv) NORTE-01-0145-FEDER-000069 (Healthy Waters) co-funded by European Regional Development Fund (ERDF), through North Portugal Regional Operational Programme (NORTE2020), under the PORTUGAL 2020 Partnership Agreement. The authors also acknowledge Águas do Norte, S.A. for supporting the development of this work. Daniela F.S. Morais acknowledges her Ph.D. scholarship supported by FCT (SFRH/BD/146476/2019). Bianca M. Souza Chaves gratefully acknowledges her postdoctoral scholarship supported by CNPq through the Science Without Borders Program (Process No. 201989/2014-0). Vítor J.P. Vilar acknowledges the FCT Individual Call to Scientific Employment Stimulus 2017 (CEECIND/01317/2017) SI

15 pages, 6 figures, 3 tables, Organophosphate flame retardants (OPFRs) are (re-)emergent environmental pollutants increasingly being used because of the restriction of other flame retardants. The chlorinated OPFR, tris(1,3-dichloro-2-propyl) phosphate (TDCPP) is among those of highest environmental concern, but its potential effects in the marine environment have rarely been investigated. We exposed a widely used sentinel marine mussel species, Mytilus galloprovincialis, to 10 μg L−1 of TDCPP during 28 days and studied: (i) the kinetics of bioaccumulation and elimination of the compound, (ii) the effect on two molecular biomarkers, glutathione S-transferase (GST) and acetylcholinesterase (AChE) activities, and (iii) proteomic alterations in the gills, following an isobaric labeling quantitative shotgun proteomic approach, at two exposure times (7 and 28 days). Uptake and elimination of TDCPP by mussels were very fast, and the bioconcentration factor of this compound in mussels was 147 L kgww-1, confirming that this compound is not very bioaccumulative, as predicted by its chemical properties. GST activity was not affected by TDCPP exposure, but AChE activity was inhibited by TDCPP at both 7 and 28 days of exposure. Proteomic analysis revealed subtle effects of TDCPP in mussel gills, since few proteins (less than 2 % of the analysed proteome) were significantly affected by TDCPP, and effect sizes were low. The most relevant effects detected were the up-regulation of epimerase family protein SDR39U1, an enzyme that could be involved in detoxification processes, at both exposure times, and the down-regulation of receptor-type tyrosine-protein phosphatase N2-like (PTPRN2) after 7 days of exposure, which is involved in neurotransmitter secretion and might be related to the neurotoxicity described for this compound. Exposure time rather than TDCPP exposure was the most important driver of protein abundance changes, with 33 % of the proteome being affected by this factor, suggesting that stress caused by laboratory conditions could be an important confounding factor that needs to be controlled in similar ecotoxicology studies. Proteomic data are available via ProteomeXchange with identifier PXD019720, L.E. F.-G. is supported with a predoctoral fellowship from Xunta de Galicia (Consellería de Cultura, Educación e Ordenación Universitaria grant ED481A-2017/298) partially co-founded by operative program FSE Galicia 2014-2020. M.C. is supported by the Ramón y Cajal contract (Ministry of Science and Innovation of Spain). This study was funded by Xunta de Galicia (refs. ED431C 2017/36, ED431C 2017/46, ED431C 2020/05 and IN607B 2018/10) and the Spanish Agencia Estatal de Investigación (refs. CTM2017-84763-C3-R-2 and CTM2016-77945-C3), partially co-funded by the European Regional Development Fund (FEDER/ERDF)

The hypothesis that exposure to certain environmental chemicals during early life stages may disrupt reproduction across multiple non-exposed generations has significant implications for understanding disease etiology and adverse outcomes. We demonstrate here reproductive multi and transgenerational effects, at environmentally relevant levels, of one of the most prescribed human pharmaceuticals, simvastatin, in a keystone species, the amphipod Gammarus locusta. The transgenerational findings has major implications for hazard and risk assessment of pharmaceuticals and other contaminants of emerging concern given that transgenerational effects of environmental chemicals are not addressed in current hazard and risk assessment schemes. Considering that the mevalonate synthesis, one of the key metabolic pathways targeted by simvastatin, is highly conserved among metazoans, these results may also shed light on the potential transgenerational effects of simvastatin on other animals, including humans. This research was funded by COMPETE 2020, Portugal 2020, the European Union through the ERDF and the Portuguese Foundation for Science and Technology – FCT (Transobesogen project – Trans-phyletic obesogenic responses: from epigenetic modules to transgenerational environmental impacts, reference: PTDC/CTA-AMB/31544/2017 – NORTE-01-0145-FEDER-031544). This research was also supported by the National Funds through FCT under the projects (UIDB/04423/2020; UIDP/04423/2020), by the Spanish Agencia Estatal de Investigación (CTM2017-84763-C3-2-R), and by the Galician Council of Culture, Education and Universities (ED431C2017/36), cofounded by ERDF. A PhD grant awarded to Susana Barros (PD/BD/143090/2018) was funded by the FCT SI

This work studies the chlorination and monochloramination reaction kinetics of two phenazone-type drugs (phenazone – Phe and propyphenazone – PrPhe) and three metabolites of phenazone-type drugs (4-formylaminoantipyrine – FAA, 4-aminoantipyrine - AA and 4-acetoamidoantipyrine - AAA). Kinetics were faster with chlorine (apparent second-order constants between 100 and 66,500 times higher) than with monochloramine. For FAA and AAA, no significant reaction was observed during monochloramination. Further, apparent rate constants decreased as the pH increased from pH 5.7 to 8.3, except during chlorination of AA. The transformation products (TPs) formed were also elucidated by liquid chromatography-high resolution mass spectrometry. The main transformation pathway for Phe and PrPhe consisted of halogenations, hydroxylations and dealkylations, while AAA and FAA were firstly transformed to AA, then followed by pyrazole ring opening and hydroxylations. The extend of the reaction was also tested in real water samples, where, in general, slower reaction kinetics were obtained during monochloramination, while the chlorination reaction showed similar half-lives to ultrapure water. Finally, acute and chronic toxicity of the TPs were estimated using two quantitative structure-activity relationship (QSAR) software (ECOSAR and TEST), showing that some TPs could be more toxic than their precursor compounds This research was funded by Xunta de Galicia (ED431C2017/36), Spanish Agencia Estatal de Investigación (ref. CTM2017-84763-C3-R-2) and FEDER/ERDF funds. This research has been co-financed by the European Regional Development Fund through the Interreg V-A Spain-Portugal Programme (POCTEP) 2014–2020 (ref. 0725_NOR_WATER_1_P). It only reflects the author's view, thus Programme authorities are not liable for any use that may be made of the information contained therein. SI

Simvastatin (SIM), a hypocholesterolaemic drug belonging to the statins group, is a widely prescribed pharmaceutical for prevention of cardiovascular diseases. Several studies showed that lipophilic statins, as SIM, cross the blood-brain barrier and interfere with the energy metabolism of the central nervous system in humans and mammalian models. In fish and other aquatic organisms, the effects of SIM on the brain energy metabolism are unknown, particularly following exposure to low environmentally relevant concentrations. Therefore, the present study aimed at investigating the influence of SIM on gene signaling pathways involved in brain energy metabolism of adult zebrafish (Danio rerio) following chronic exposure (90 days) to environmentally relevant SIM concentrations ranging from 8 ng/L to 1000 ng/L. Real-time PCR was used to determine the transcript levels of several genes involved in different pathways of the brain energy metabolism (glut1b, gapdh, acadm, accα, fasn, idh3a, cox4i1, and cox5aa). The findings here reported integrated well with ecological and biochemical responses obtained in a parallel study. Data demonstrated that SIM modulates transcription of key genes involved in the mitochondrial electron transport chain, in glucose transport and metabolism, in fatty acid synthesis and β-oxidation. Further, SIM exposure led to a sex-dependent transcription profile for some of the studied genes. Overall, the present study demonstrated, for the first time, that SIM modulates gene regulation of key pathways involved in the energy metabolism in fish brain at environmentally relevant concentrations This study was developed under the project Nor-Water -Poluentes emergentes nas águas da Galiza-Norte de Portugal: novas ferramentas para gestão de risco [Reference: 0725_NOR_WATER_1_P], financed by Programa de Cooperação Interreg Portugal/Espanha, (POCTEP) 2014–2020. The study was also supported by the National Funds through Portuguese Foundation for Science and Technology (FCT) under the projects [UID/Multi/04423/2019 and UID/AGR/04033/2013]. S. Barros was supported by the doctoral fellowship [PD/BD/143090/2018] from FCT. J.B. Quintana acknowledges the financial support of Spanish “Agencia Estatal de Investigación” [ref. CTM2017-84763-C3-R-2] and Xunta de Galicia [ref. ED431C2017/36], both co-funded by FEDER/ERDF SI

Wastewater-based epidemiology (WBE) has become a very useful tool to monitor a population's drug consumption or exposure to environmental and food contaminants. In this work, WBE has been applied to estimate tobacco consumption in seven Spanish regions. To this end, 24 h composite wastewater samples were taken daily for one week in 17 wastewater treatment plants, covering altogether a population of ca. 6 million inhabitants. The samples were treated by enzymatic deconjugation and the wastewater content of two human-specific nicotine metabolites (namely, cotinine and trans-3′-hydroxycotinine) was measured to estimate the daily consumption of nicotine. The population-weighted average nicotine consumption in the seven analyzed regions was 2.2 g/(day∙1000 inh.), without any daily pattern. This average estimated nicotine consumption value agreed with the value derived from official tobacco sales data. Differences in consumption among the seven studied regions were found, being Galicia, the region with the lowest rate, and the Basque Country and Catalonia those with the highest rates. However, no conclusive correlation was found between those values and the prevalence data taken from two different national surveys, nor sociodemographic and health data. This study demonstrates that this tool can complement other indicators in order to accurately assess tobacco consumption rates at regional and national levels and provides the most extensive application of the approach in the Spanish territory., Financial support This study was supported by MINECO/AEI projects (CTM2016-81935-REDT, CTM2017-84763-C3-2-R, CTM2017-84763-C3-1-R, CTM2017-84763-C3-3-R), MICINN project (CEX2018-000794-S), Galician Council of Culture, Education and Universities (ED481D 2017/003 and ED431C2017/36), cofunded by FEDER/ERDF.

This is a post-peer-review, pre-copyedit version of an article published in Analytical and Bioanalytical Chemistry. The final authenticated version is available online at: https://doi.org/10.1007/s00216-020-02434-w A new analytical method for the determination of 22 perfluoroalkylated (carboxylic and sulfonic) acids in water samples is presented. The method's objective was to achieve the simultaneous quantification of compounds with different chain lengths (from C1 to C18). To this end, 500 mL of water were extracted with Oasis WAX solid-phase extraction cartridges and eluted with 3 mL of 5% ammonia in methanol. After evaporation to dryness, extracts were reconstituted in methanol:ultrapure water (1:1) and analyzed by mixed-mode liquid chromatography-tandem mass spectrometry (MMLC-MS/MS) using a weak anion exchange/reversed-phase column. The method provided good results, with limits of quantification lower than 1 ng/L in river water for most of compounds, except the two perfluorocarboxylic acids with the longest alkyl chain (>C14) and trifluoroacetic acid, for which a blank contamination problem was observed. The method proved good trueness and precision in both ultrapure and river water (R ≥ 81%, RSD ≤ 15%). After validation, the method was applied to the analysis of nine water samples where nine perfluoroalkylated acids were quantified. Seven of them were ultrashort- (C1-C4) and short-chain (C4-C8) perfluoroalkylated acids, pointing out the importance of developing methods capable to target such substances for further monitoring This work was supported by the Water Challenges for a Changing World Joint Program Initiative (Water JPI) Pilot Call (ref. WATERJPI2013 – PROMOTE), the Spanish Ministry of Economy and Competitiveness/Spanish Agencia Estatal de Investigación (refs. JPIW2013-117 and CTM2017-84763-C3-2-R), the Galician Council of Culture, Education and Universities (ref. ED431C2017/36) and FEDER/EDRF funding SI

Background and aims Wastewater‐based epidemiology is an additional indicator of drug use that is gaining reliability to complement the current established panel of indicators. The aims of this study were to: (i) assess spatial and temporal trends of population‐normalized mass loads of benzoylecgonine, amphetamine, methamphetamine and 3,4‐methylenedioxymethamphetamine (MDMA) in raw wastewater over 7 years (2011–17); (ii) address overall drug use by estimating the average number of combined doses consumed per day in each city; and (iii) compare these with existing prevalence and seizure data. Design Analysis of daily raw wastewater composite samples collected over 1 week per year from 2011 to 2017. Setting and Participants Catchment areas of 143 wastewater treatment plants in 120 cities in 37 countries. Measurements Parent substances (amphetamine, methamphetamine and MDMA) and the metabolites of cocaine (benzoylecgonine) and of Δ9‐tetrahydrocannabinol (11‐nor‐9‐carboxy‐Δ9‐tetrahydrocannabinol) were measured in wastewater using liquid chromatography–tandem mass spectrometry. Daily mass loads (mg/day) were normalized to catchment population (mg/1000 people/day) and converted to the number of combined doses consumed per day. Spatial differences were assessed world‐wide, and temporal trends were discerned at European level by comparing 2011–13 drug loads versus 2014–17 loads. Findings Benzoylecgonine was the stimulant metabolite detected at higher loads in southern and western Europe, and amphetamine, MDMA and methamphetamine in East and North–Central Europe. In other continents, methamphetamine showed the highest levels in the United States and Australia and benzoylecgonine in South America. During the reporting period, benzoylecgonine loads increased in general across Europe, amphetamine and methamphetamine levels fluctuated and MDMA underwent an intermittent upsurge. Conclusions The analysis of wastewater to quantify drug loads provides near real‐time drug use estimates that globally correspond to prevalence and seizure data., This study was supported by the following countries, institutions and projects Australia: Thyne Reid foundation; Canada: Natural Sciences and Engineering Research Council of Canada (NSERC); Iceland: The Icelandic Research Fund (Grant number 163049–051); Slovenia: Slovene Research Agency (funding Project L1–9191); Spain: MINECO/AEI projects (CTM2014–56628‐C3–2‐R, CTQ2015–65603‐P, CTM2016–81935‐REDT, CTM2017–84763‐C3–2‐R), Galician Council of Culture, Education and Universities (ED481D 2017/003); UK: Environmental Sustainability Knowledge Transfer Network, Engineering and Physical Sciences Research Council and Thermo Fisher Scientific (CASE industrial scholarship for K. Munro, Ref.: EP/J502029/1). European Monitoring Centre for Drugs and Drug Addiction (EMCDDA); EU International Training Network SEWPROF (Marie Curie‐FP7‐PEOPLE, grant number 317205); COST Action ES1307 supported by COST (European Cooperation in Science and Technology); WATCH (Wastewater Analysis of Traces of illicit drug‐related Chemicals for law enforcement and public Health DG migration and Home affairs ‐ HOME/2015/ISFP/PR/DRUG/0062). Sampling support and provision of catchment information Austria: Klemens Geiger and Michael Schlapp; Belgium: Jonathan Phariseau, Bart Coene, Luc Van Os, Peter Nys, Dieter Lemaire, Jean‐François Mougel, Patrick Vantroyen and Karel Claes; Croatia: Marin Ganjto; Czech Republic: Jiri Stara and Robert Hrich Brněnské; France: Véronique Bremont; Italy: Roberto Mazzini and Francesca Pizza (Milan), Francesco Avolio (Bologna), Fabrizio Moratto and Sergio Ghezzi (Gorizia), Rosanna Brienza and Simona Panariello (Potenza), Pier Paolo Abis and Antonia Attanasio (Bari), Antonella Cicala (Palermo); Norway: Pia Ryrfors; Portugal: João Goulão, José Martins, Pedro Alvaro and Fátima Paixão; Slovakia: Silvia Antalová and Jozef Tichy; Spain: Begoña Martínez López, Cristian Mesa, Santiago Querol Rodriguez, Fernando Llavador, Enrique Albors and Gloria Fayos; the Netherlands: Alex Veltman, Peter Theijssen, Peter van Dijk, Stefan Wijers, Mark Stevens, Ferry de Wilde. Analytical support Australia: Maulik Ghetia; Cyprus: Popi Karaolia; Greece: Nikoilaos Raikos; Spain: Ana Maria Botero‐Coy, Clara Boix, Alberto Celma, Jorge Pitarch, Inés Racamonde and Eddie Fonseca; Italy: Emma Gracia‐Lor, Nikolaos I. Rousis and Noelia Salgueiro‐Gonzalez. Data repository and data screening Eawag: Harald von Waldow; EMCDDA: Renate Hochwieser, Liesbeth Vandam, João Matias and Federica Mathis.

A novel approach based on the direct pulsed irradiation of UV-C light onto ibuprofen (IBP) solutions was evaluated in this work, as proof of concept for the direct removal of micropollutants. The experiments confirmed that laser irradiation is able to completely degrade IBP in 15 min in distilled water, with a DOC depletion of ca. 25% and with transformation products (TPs) remaining in solution and estimated to represent ca. 10% of the initial IBP concentration. In wastewater spiked samples, removal efficiency is slightly lower but still significant (ca. 5% IBP remaining after 15 min). Hence, this work suggests that low power solid state pulsed lasers, emitting at 266 nm wavelength, show promise for the removal of these type of micropollutants from water. These results open new opportunities towards the development of chemical-free water treatment methods based on direct, selective irradiation using state of the art, miniaturized laser devices., This research was partially supported by the Consellería de Educación Program for Development of a Strategic Grouping in Materials - AeMAT at the University of Santiago de Compostela under the Grant No. ED431E2018/08. C. Bao-Varela, B.J. Sieira, J.B. Quintana and R. Rodil also acknowledge Xunta de Galicia (ref. ED431B 2017/64, ref. ED431C2017/36) and Spanish Agencia Estatal de Investigación (CTM2017-84763-C3-R-2). Several of the above mentioned projects are cofounded by the European Regional Development Fund. G.F.F. & L.A.A. acknowledge support from Gobierno de Aragón “Construyendo Europa desde Aragón” (research group T54_20R).

Background In this study, an alternative and complementary method to those approaches currently used to estimate alcohol consumption by the population is described. This method, known as wastewater-based epidemiology (WBE), allows back-calculating the alcohol consumption rate in a given population from the concentrations of a selected biomarker measured in wastewater. Methods Composite (24-h) wastewater samples were collected at the inlet of 17 wastewater treatment plants located in 13 Spanish cities for seven consecutive days in 2018. The sampled area covered 12.8% of the Spanish population. Wastewater samples were analyzed to determine the concentration of ethyl sulfate, the biomarker used to back-calculate alcohol consumption. Results Alcohol consumption ranged from 4.5 to 46 mL/day/inhabitant. Differences in consumption were statistically significant among the investigated cities and between weekdays and weekends. WBE-derived estimates of alcohol consumption were comparable to those reported by its corresponding region in the Spanish National Health Survey in most cases. At the national level, comparable results were obtained between the WBE-derived annual consumption rate (5.7 ± 1.2 L ethanol per capita (aged 15+)) and that reported by the National Health Survey (4.7 L ethanol per capita (aged 15+)). Conclusions This is the largest WBE study carried out to date in Spain to estimate alcohol consumption rates. It confirms that this approach is useful for establishing spatial and temporal patterns of alcohol consumption, which could contribute to the development of health care management plans and policies. Contrary to established methods, it allows obtaining information in a fast and relatively economical way., The authors would like to acknowledge all the city councils of the cities participating in this study for their collaboration as well as the operators of the WWTPs for their assistance in the collection of the wastewater samples, especially to: Cristian Mesa and Angela Vidal from Aigues de Barcelona (Barcelona WWTP), Jordi Palatsi from Aqualia (Lleida WWTP), Viaqua and Concello de Santiago de Compostela, the Public Entity of Wastewater Treatment (EPSAR) of the Generalitat Valenciana and especially to Fernando Llavador. Luis Aceiton, Enrique Albors, Angel Jiménez, Maria José Tarrega, Sonia Tristante and all the personal of the WWTPs (Aguas de Valencia, Spain), Sociedad de Fomento Agrícola Castellonense (FACSA, Castellón), and especially WWTP operators Santiago Querol and Sara Gargallo are acknowledged for providing wastewater samples from Castellón, as well as Subdirección General de Gestión del Agua, Ayuntamiento de Madrid, for allowing the collection of samples from Madrid.

In this chapter we review different applications based on sorptive extractions in solid supports for the analysis of organic pollutants in environmental water samples. Among sorptive extractions, solid phase extraction, solid phase microextraction, stir-bar sorptive extraction, and microextraction by packed sorbent are the main techniques covered. We discuss the different applications of these techniques according to their physicochemical properties into four main groups of compounds (volatile, hydrophobic, moderately polar, and highly polar), since such properties have a clear impact on the methodology employed.

The photocatalytic activity of TiO2 nanoparticles (NPs) supported on mesoporous silica SBA-15 (TiO2/SBA-15) was evaluated for the photodegradation of sulfadiazine (SDZ), as target contaminant of emerging concern (CEC), using either pure water solutions (PW) or a real secondary urban wastewater (UWW) spiked with SDZ. For this purpose, TiO2/SBA-15 samples with 10, 20 and 30% TiO2 (w/w) were prepared by the sol-gel post synthetic method on pre-formed SBA-15, using titanium (IV) isopropoxide as a precursor. The TiO2/SBA-15 materials were characterized by HRTEM, SAXS and XRD, nitrogen adsorption isotherms and UV–vis diffuse reflectance spectroscopy. TiO2 NPs were shown to be attached onto the external surface, decorating the SBA-15 particles. The TiO2/SBA-15 catalysts were active in SDZ photodegradation using the annular FluHelik photoreactor, when irradiated with UVA light. The 30% TiO2/SBA-15 sample presented the best performance in optimization tests performed using PW, and it was further used for the tests with UWW. The photocatalytic activity of 30% TiO2/SBA-15 was higher (56% SDZ degradation) than that of standard TiO2–P25 (32% SDZ degradation) in the removal of SDZ spiked in the UWW ([SDZ] = 2 mg L−1). The photodegradation of SDZ with 30% TiO2/SBA-15 eached 90% for UWW spiked with a lower SDZ concentration ([SDZ] = 40 μg L−1). Aside of SDZ, a suit of 65 other CECs were also identified in the UWW sample using LC-MS spectrometry. A fast-screening test showed the heterogeneous photocatalytic system was able to remove most of the detected CECs from UWW, by either adsorption and/or photocatalysis. SB and ACSCT acknowledge the São Paulo Research Foundation (FAPESP) for the financial support (grants #2016/05496–2 and #2018/21271–6, respectively). BC thanks the National Council for Scientific and Technological Development (CNPq) (grant #204891/2018–3) for supporting the interchange research period at Faculty of Engineering University of Porto (Portugal). ACSCT also thanks the National Council for Scientific and Technological Development (CNPq) (grant #307481/2017–4). The authors thank the Multiuser Central Facilities (UFABC) for the analytical support. This work was also financially supported by the i) Base Funding - UIDB/50020/2020 of the Associate Laboratory LSRE-LCM - funded by national funds through FCT / MCTES (PIDDAC); ii) the European Regional Development Fund (ERDF) through the Interreg V-A Spain-Portugal Programme (POCTEP) 2014–2020 (ref. 0725_NOR_WATER_1_P). Vítor J.P. Vilar acknowledges the FCT Individual Call to Scientific Employment Stimulus 2017 (CEECIND/01317/2017). The team of the University of Santiago acknowledges funding by Xunta de Galicia (ED431C2017), the Spanish Agencia Estatal de Investigación (ref. CTM 2017-84763-C3-R-2), partly cofounded by the ERDF. 2023-08-24 SI

This work investigates the reaction of 1-vinyl-2-pyrrolidinone (VP) and 2-piperazin-1-yletanamine (PPE) under UV radiation. Both substances are high-volume production chemicals (production >1000 tons/year) widely used in polymers, coatings and a wide array of applications, which have been classified as mobile chemicals and which can then lead to the formation of persistent and mobile transformation products (TPs). Thus, their reaction with UV light was studied by means of liquid chromatography-quadrupole-time-of-flight-mass spectrometry (LC-QTOF-MS). Both compounds presented a high reactivity, the VP quantum yield was 0.28 mol/E; whereas, PPE had a quantum yield notably higher than 1 (16 mol/E). Five and 7 TPs were identified for VP and PPE, respectively. Some of them had been already reported in literature due to sunlight photodegradation or other oxidation processes, but most of them are reported here for the first time. Finally, the acute and chronical toxicity of precursors and TPs were estimated using two quantitative structure-activity relationship (QSAR) software tools which led to some discrepancies in the estimations, pointing to the need for experimental toxicity assays for these compounds This work was supported by the Water Challenges for a Changing World Joint Program Initiative (Water JPI) Pilot Call (ref. WATERJPI2013 – PROMOTE), funded by the Spanish Ministry of Economy and Competitiveness/Spanish Agencia Estatal de Investigación (refs. JPIW 2013-117, CTM2017-84763-C3-2-R and PID2020-117686RB-C32). We also acknowledge the Galician Council of Culture, Education and Universities (ref. ED431C2021/06). This research has been co-financed by the European Regional Development Fund through the Interreg V-A Spain-Portugal Programme (POCTEP) 2014–2020 (ref. 0725_NOR_WATER_1_P). It only reflects the author's view; thus, Programme authorities are not liable for any use that may be made of the information contained therein. SI

Copyright © 2021 Elsevier Ltd. All rights reserved., Several studies show that many water bodies in developing countries are increasingly affected by anthropogenic pressure, such as agricultural activities, domestic and industrial wastewater. However, data is scarce in several of such countries, including Panama. Thus, in this work, the ecotoxicological status of selected rivers in Panama with distinct input sources were evaluated using the zebrafish (Danio rerio) embryo bioassays combined with a liquid chromatography-high resolution mass spectrometry screening of contaminants of emerging concern (CECs), using a library of over 3200 chemicals. A total of 68 CECs, including pharmaceuticals and metabolites, pesticides and several industrial chemicals, could be tentatively identified. Additionally, the zebrafish embryo bioassays showed a significant increase (p < 0.05) in embryo mortality/abnormalities when incubated with water samples from two rivers, Matasnillo and Curundú (47.5% and 32%, respectively). Importantly, a positive correlation between ecotoxicological endpoints and some of the detected CECs was observed. The findings demonstrate that both rivers are under strong anthropogenic pressure, and therefore, management actions are urgently needed to decrease their level of contamination. Overall, this study further supports the use of the zebrafish embryo bioassay as a fast, high throughput approach for screening the toxicity of water samples, and highlights the advantages of combining ecotoxicological assays with high-resolution mass spectrometry to an expedite assessment of the ecotoxicological status of water bodies., This work was supported by the Portuguese Foundation for Science and Technology (FCT) (PTDC|CTA-AMB|31554|2017; UIDB/04423/2020; UIDP/04423/2020), the Spanish Agencia Estatal de Investigacion (ref. CTM2017-84763-C3-2-R), the Galician Council of Culture, Education and Universities (ref. ED431C2017/36 and Veronica Castro predoctoral contract, ref. ED481A-2017/156), co-funded by the European Regional Development Fund (ERDF/FEDER).

The presence of persistent and mobile organic contaminants (PMOC) in aquatic environments is a matter of high concern due to their capability of crossing through natural and anthropogenic barriers, even reaching drinking water. Most analytical methods rely on reversed-phase liquid chromatography (RPLC), which is quite limited for the detection of very polar chemicals. Thus, many of these PMOCs may have not been recognized as water pollutants yet, due to the lack of analytical methods capable to detect them. Mixed-mode LC (MMLC), providing the combination of RP and ion-exchange functionalities is explored in this work with a trifunctional column, combining RPLC, anion and cation exchange, which allows the simultaneous determination of analytes with extremely different properties. A nondiscriminant sample concentration step followed by a MMLC-high resolution mass spectrometry method was developed for a group of 37 very polar model chemicals with different acid/base functionalities. The overall method performance was satisfactory with a mean limit of detection of 50 ng/L, relative standard deviation lower than 20% and overall recoveries (including matrix effects) higher than 60% for 54% of model compounds. Then, the method was applied to 15 real water samples, by a suspect screening approach. For those detected PMOC with standard available, a preliminary estimation of concentrations was also performed. Thus, 22 compounds were unequivocally identified in a range of expected concentrations from 6 ng/L to 540 μg/L. Some of them are well-known PMOC, such as acesulfame, perfluorobutanoic acid or metformin, but other novel pollutants were also identified, as for example di-o-tolylguanidine or trifluoromethanesulfonic acid, which had not or were scarcely studied in water so far.

The growing concern regarding the negative effects of solar radiation on the skin has led to a drastic increase in the use of sunscreens containing in its composition up to 10% of aromatic chemicals, such as ethylhexyl dimethyl p-aminobenzoic acid (OD-PABA) and octocrylene (OC). The objective of this study was to evaluate the toxicity and to assess the environmental risk posed by these two ultraviolet filters, widely used in cosmetics and as plastic additives, in the marine environment. Several ecotoxicological bioassays were performed with three model organisms belonging to different trophic levels: the microalgae Isochrysis galbana, the mussel Mytilus galloprovincialis, and the sea urchin Paracentrotus lividus. The results show remarkable toxicity to marine species for both OD-PABA (EC10 values range 26,5–127 µg L−1) and OC (EC10 range 103–511 µg L−1). The cell division in the microalgae I. galbana was the most sensitive endpoint tested. To determine the environmental risk of these substances, the risk coefficient (RQ) was calculated. Due to the higher concentrations reported, OC showed remarkable risk (RQ = 0.27), whereas for OD-PABA the risk was low (RQ = 0.007).

A new analytical method for the determination of 22 perfluoroalkylated (carboxylic and sulfonic) acids in water samples is presented. The method's objective was to achieve the simultaneous quantification of compounds with different chain lengths (from C

This is the peer reviewed version of the following article: González‐Mariño, I, Estévez‐Danta, A, Rodil, R, et al. Profiling cocaine residues and pyrolytic products in wastewater by mixed‐mode liquid chromatography–tandem mass spectrometry. Drug Test Anal. 2019; 11: 1018– 1027, which has been published in final form at https://doi.org/10.1002/dta.2590. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions This work provides a new analytical method for the determination of cocaine, its metabolites benzoylecgonine and cocaethylene, the pyrolytic products anhydroecgonine and anhydroecgonine methyl ester, and the pharmaceutical levamisole in wastewater. Samples were solid‐phase extracted and extracts analyzed by liquid chromatography–tandem mass spectrometry using, for the first time in the illicit drug field, a stationary phase that combines reversed‐phase and weak cation‐exchange functionalities. The overall method performance was satisfactory, with limits of detection below 1 ng/L, relative standard deviations below 21%, and percentages of recovery between 93% and 121%. Analysis of 24‐hour composite raw wastewater samples collected in Santiago de Compostela (Spain) and Brasilia (Brazil) highlighted benzoylecgonine as the compound showing the highest population‐normalized mass loads (300–1000 mg/day/1000 inhabitants). In Brasilia, cocaine and levamisole loads underwent an upsurge on Sunday, indicating a high consumption, and likely a direct disposal, of cocaine powder on this day. Conversely, the pyrolytic product resulting from the smoke of crack, anhydroecgonine methyl ester, and its metabolite anhydroecgonine were relatively stable over the four days, agreeing with a non‐recreational‐associated use of crack This work was financially supported by Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia (ED431C2017/36 and IGM postdoctoral contract, Plan Galego I2C‐Modalidade B, ED481D 2017/003), Ministerio de Economía y Competitividad (project no. CTM2017‐84763‐C3‐2‐R), the Federal District Research Foundation (project no. 193.000.916/2015), and FEDER/ERDF SI

This study presents the development and validation of a new analytical method based on matrix solid-phase dispersion (MSPD), integrating sample extraction and clean-up in one single step, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the simultaneous determination of 18 organophosphorus flame retardants and/or plasticizers (OPEs) in marine mussel (Mytilus edulis and Mytilus galloprovincialis) samples. Among these OPEs, 5 (tetraethyl 1,2-ethanediylbis(phosphonate), 6H-dibenzo[c,e] [1,2]oxaphosphinine 6-oxide, tris(2,3-dibromopropyl) phosphate, 2,2-propanediyldi-4,1-phenylene bis(phosphate) and resorcinol bis(diphenyl phosphate)) are considered here for the first time in marine samples. Different parameters affecting the MSPD (clean-up sorbent and elution solvent) were optimized to obtain a good compromise between analyte recoveries and extract clean-up. Also, particular attention was paid to tackle blank issues. The overall method was validated in terms of trueness, precision and detection and quantification limits. Percentages of recovery varied from 69% to 122% with relative standard deviations below 24%. Detection limits ranged from 0.06 to 5 ng g−1 and quantification limits from 0.19 to 17 ng g−1 dry weight. Finally, the method was applied to the analysis of 7 mussel samples collected in the coast of Galicia (Spain). 8 OPEs were detected in these samples at concentrations ranging from the LOQ to 291 ng g−1 dry weight. This work was financially supported by the Spanish Agencia Estatal de Investigación (ref. CTM2017-84763-C3-2-R), the Galician Council of Culture, Education and Universities (ref. ED431C2017/36 and Verónica Castro predoctoral contract, ref. ED481A-2017/156), cofunded by FEDER/ERDF SI

This is the accepted manuscript of the following article: Espíndola et al. Science of the Total Environment, 2019, 667, 197-207. https://doi.org/10.1016/j.scitotenv.2019.02.335 An innovative photoreactor, FluHelik, was used to promote the degradation of contaminants of emerging concern (CECs) by a photochemical UVC/H2O2 process. First, the system was optimized for the oxidation of a model antibiotic, oxytetracycline (OTC), using both ultrapure water (UPW) and a real urban wastewater (UWW) (collected after secondary treatment) as solution matrices. Following, the process was evaluated for the treatment of a UWW spiked with a mixture of OTC and 10 different pharmaceuticals established by the Swiss legislation at residual concentrations (∑CECs

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Environmental Science & Technology, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see: http://dx.doi.org/10.1021/acs.est.8b03725 Lagrangian ocean analysis, where virtual parcels of water are tracked through hydrodynamic fields, provides an increasingly popular framework to predict the dispersal of water parcels carrying particles and chemicals. We conduct the first direct test of Lagrangian predictions for emerging contaminants using (1) the latitude, longitude, depth, sampling date, and concentrations of UV filters in raft cultured mussel (Mytilus galloprovincialis) of the estuary Ria de Arousa, Spain (42.5°N, 8.9°W); (2) a hydrodynamic numerical model at 300 m spatial resolution; and (3) a Lagrangian dispersion scheme to trace polluted water parcels back to pollution sources. The expected dispersal distances (mean ± SD) are 2 ± 1 km and the expected dispersal times (mean ± SD) are 6 ± 2 h. Remarkably, the probability of dispersal of UV filters from potential sources to rafts decreases 5-fold over 5 km. In addition to predicting dispersal pathways and times, this study also provides a framework for quantitative investigations of concentrations of emerging contaminants and source apportionment using turbulent diffusion. In the coastline, the ranges of predicted concentrations of the UV-filters 4-methylbenzylidene-camphor, octocrylene, and benzophenone-4 are 3.2 × 10–4 to 0.023 ng/mL, 2.3 × 10–5 to 0.009 ng/mL, and 5.6 × 10–4 to 0.013 ng/mL, respectively. At the outfalls of urban wastewater treatment plants these respective ranges increase to 8.9 × 10–4 to 0.07 ng/mL, 6.2 × 10–5 to 0.027 ng/mL, and 1.6 × 10–3 to 0.040 ng/mL. This research is supported by the Spanish State Research Agency projects CTM2014-56628-C3-2-R, CTM2014-56628-C3-3-R, CTM2017-84763-C3-2-R, CTM2017-84763-C3-3-R, and CTM2017-90890-REDT (MINECO/AEI/FEDER, EU). This work used the Extreme Science and Engineering Discovery Environment (XSEDE), which is supported by the National Science Foundation grant number NSF-OCE170005 SI

This works investigates the chlorination and bromination of two rubber and polymer related chemicals, which have emerged as relevant water contaminants, i.e. 1,3-di-o-tolylguanidine (DTG) and 1,3-diphenylguanidine (DPG). Kinetic constants at different pH values were obtained and modelled, taking into account the pKa values of DTG/DPG and HClO, showing that the maximum reaction rate (kapp > 104 M−1 s−1) is obtained at pH values 8.8 for DPG and 9.1 for DTG. Bromination is also very fast, although unlike chlorination, deviation from the model was observed at neutral pH, which was attributed to formation of metastable transformation product (TP). A total of 35 TPs, corresponding to halogenation, hydroxylation, formation of monophenylguanidine derivatives and cyclization reactions, were tentatively identified. Furthermore it was found that chloroform can be formed up to a 25% molar yield, while dichloroacetonitrile was formed into less than a 3% yield. Several ecotoxicological endpoints were predicted by quantitative structure–activity relationship models (QSAR) for the TPs, some of which were predicted to be more toxic than DPG/DTG. Also a chlorinated solution investigated by a Vibrio Fisheri acute toxicity test, confirmed that toxicity increases with chlorination. This work was supported by the Water Challenges for a Changing World Joint Program Initiative (Water JPI) Pilot Call (ref. WATERJPI2013 – PROMOTE), funded by the Spanish Ministry of Economy and Competitiveness/Spanish Agencia Estatal de Investigación (refs. JPIW2013-117 and CTM2017-84763-C3-2-R) and French Office National de l’Eau et des Milieux Aquatiques (ref. PROMOTE). We also acknowledge the Galician Council of Culture, Education and Universities (ref. ED431C2017/36), Région Nouvelle Aquitaine and FEDER/EDRF funding. Benigno J. Sieira acknwledges the COST (European Cooperation in Science and Technology) Action ES1307 for suporting his research stay in Poitiers SI

This is the postprint (accepted manuscript) version of the article published by Taylor & Francis in the International Journal of Environmental Analytical Chemistry on December, 10th 2018. Available on-line: http://www.tandfonline.com//10.1080/03067319.2018.1554743 The levels of cocaine (COC) and its metabolites benzoylecgonine (BE) and cocaethylene (COE) in wastewater samples from Brasilia, Brazil, were determined using liquid chromatography coupled to hybrid quadrupole-time-of-flight mass spectrometry. The former metabolite was used to estimate cocaine consumption using a country-tuned correction factor that considers BE excretion rates for different routes of administration as well as the fraction of crack users in Brazil. A day-to-day analysis during a week indicates higher cocaine use in weekends with peaks on Sunday in both southern (7385 ± 121 mg day−1 1000 inhab−1) and northern (3566 ± 171 mg day−1 1000 inhab−1) areas of Brasilia. A significant high cocaine use was also observed in the Carnival Day of 2018 (6229 ± 219 mg day−1 1000 inhab−1). COE/BE ratios were used to assess COC and alcohol co-consumption since COE is produced during the co-consumption of both substances. Higher ratios were also observed during the weekend. However, higher ratios on Saturdays rather than Sundays may be explained by the decrease of BE excretion during the co-consumption with alcohol, which may lead to an underestimation of the cocaine use estimates on Saturdays, as well as by different patterns of co-consumption by powder and crack users, where the latter usually drink lower amounts of alcohol. Our data suggest that only 3% of cocaine was seized by the local Technical Police during the study This work was supported by the Federal District Research Foundation under Grant [193.000.916/ 2015]; the Spanish Agencia Estatal de Investigación under Grant [CTM2017-84763-C3-2-R]; the Galician Council of Culture, Education and Universities under Grants [ED431C2017/36]; IGM postdoctoral contract, Plan Galego I2C-Modalidade B, ED481D 2017/003; and FEDER/ERDF SI