Comparison of phosphodiesterase type V inhibitors use in eight European cities through analysis of urban wastewater

In this work a step forward in investigating the use of prescription drugs, namely erectile dysfunction products, at European level was taken by applying the wastewater-based epidemiology approach. 24-h composite samples of untreated wastewater were collected at the entrance of eight wastewater treatment plants serving the catchment within the cities of Bristol, Brussels, Castellón, Copenhagen, Milan, Oslo, Utrecht and Zurich. A validated analytical procedure with direct injection of filtered aliquots by liquid chromatography-tandem mass spectrometry was applied. The target list included the three active pharmaceutical ingredients (sildenafil, tadalafil and vardenafil) together with (bio)transformation products and other analogues. Only sildenafil and its two human urinary metabolites desmethyl- and desethylsildenafil were detected in the samples with concentrations reaching 60 ng L−1. The concentrations were transformed into normalized measured loads and the estimated actual consumption of sildenafil was back-calculated from these loads. In addition, national prescription data from five countries was gathered in the form of the number of prescribed daily doses and transformed into predicted loads for comparison. This comparison resulted in the evidence of a different spatial trend across Europe. In Utrecht and Brussels, prescription data could only partly explain the total amount found in wastewater; whereas in Bristol, the comparison was in agreement; and in Milan and Oslo a lower amount was found in wastewater than expected from the prescription data. This study illustrates the potential of wastewater-based epidemiology to investigate the use of counterfeit medication and rogue online pharmacy sales

Transformation and sorption of illicit drug biomarkers in sewer biofilms

In-sewer transformation of drug biomarkers (excreted parent drugs and metabolites) can be influenced by the presence of biomass in suspended form as well as attached to sewer walls (biofilms). Biofilms are likely the most abundant and biologically active biomass fraction in sewers. In this study, 16 drug biomarkers were selected, including the parent forms and the major human metabolites of mephedrone, methadone, cocaine, heroin, codeine, and tetrahydrocannabinol (THC). Transformation and sorption of these substances were assessed in targeted batch experiments using laboratory-scale biofilm reactors operated under aerobic and anaerobic conditions. A one-dimensional model was developed to simulate diffusive transport, abiotic and biotic transformation, and partitioning of drug biomarkers. Model calibration to experimental results allowed estimating biotransformation rate constants in sewer biofilms, which were compared to those obtained for suspended biomass. Our results suggest that sewer biofilms can enhance the biotransformation kinetics of most selected compounds. Through scenario simulations, we demonstrated that the estimation of biotransformation rate constants in biofilm can be significantly biased if the boundary layer thickness is not accurately estimated. This study complements our previous investigation on the transformation and sorption of drug biomarkers in the presence of only suspended biomass in untreated sewage. A better understanding of the role of sewer biofilms—also relative to the in-sewer suspended solids—and improved prediction of associated fate processes can result in more accurate estimation of daily drug consumption in urban areas in wastewater-based epidemiological assessments

Comparative measurement and quantitative risk assessment of alcohol consumption through wastewater-based epidemiology: An international study in 20 cities

Quantitative measurement of drug consumption biomarkers in wastewater can provide objective information on community drug use patterns and trends. This study presents the measurement of alcohol consumption in 20 cities across 11 countries through the use of wastewater-based epidemiology (WBE), and reports the application of these data for the risk assessment of alcohol on a population scale using the margin of exposure (MOE) approach. Raw 24-h composite wastewater samples were collected over a one-week period from 20 cities following a common protocol. For each sample a specific and stable alcohol consumption biomarker, ethyl sulfate (EtS) was determined by liquid chromatography coupled to tandem mass spectrometry. The EtS concentrations were used for estimation of per capita alcohol consumption in each city, which was further compared with international reports and applied for risk assessment by MOE. The average per capita consumption in 20 cities ranged between 6.4 and 44.3 L/day/1000 inhabitants. An increase in alcohol consumption during the weekend occurred in all cities, however the level of this increase was found to differ. In contrast to conventional data (sales statistics and interviews), WBE revealed geographical differences in the level and pattern of actual alcohol consumption at an inter-city level. All the sampled cities were in the “high risk” category (MOE < 10) and the average MOE for the whole population studied was 2.5. These results allowed direct comparisons of alcohol consumption levels, patterns and risks among the cities. This study shows that WBE can provide timely and complementary information on alcohol use and alcohol associated risks in terms of exposure at the community level

Estimation of caffeine intake from analysis of caffeine metabolites in wastewater

Caffeine metabolites in wastewater were investigated as potential biomarkers for assessing caffeine intake in a population. The main human urinary metabolites of caffeine were measured in the urban wastewater of ten European cities and the metabolic profiles in wastewater were compared with the human urinary excretion profile. A good match was found for 1,7-dimethyluric acid, an exclusive caffeine metabolite, suggesting that might be a suitable biomarker in wastewater for assessing population-level caffeine consumption. A correction factor was developed considering the percentage of excretion of this metabolite in humans, according to published pharmacokinetic studies. Daily caffeine intake estimated from wastewater analysis was compared with the average daily intake calculated from the average amount of coffee consumed by country per capita. Good agreement was found in some cities but further information is needed to standardize this approach. Wastewater analysis proved useful to providing additional local information on caffeine use

Wastewater-based epidemiology to assess pan-European pesticide exposure

Human biomonitoring, i.e. the determination of chemicals and/or their metabolites in human specimens, is the most common and potent tool for assessing human exposure to pesticides, but it suffers from limitations such as high costs and biases in sampling. Wastewater-based epidemiology (WBE) is an innovative approach based on the chemical analysis of specific human metabolic excretion products (biomarkers) in wastewater, and provides objective and real-time information on xenobiotics directly or indirectly ingested by a population. This study applied the WBE approach for the first time to evaluate human exposure to pesticides in eight cities across Europe. 24 h-composite wastewater samples were collected from the main wastewater treatment plants and analyzed for urinary metabolites of three classes of pesticides, namely triazines, organophosphates and pyrethroids, by liquid chromatography-tandem mass spectrometry. The mass loads (mg/day/1000 inhabitants) were highest for organophosphates and lowest for triazines. Different patterns were observed among the cities and for the various classes of pesticides. Population weighted loads of specific biomarkers indicated higher exposure in Castellon, Milan, Copenhagen and Bristol for pyrethroids, and in Castellon, Bristol and Zurich for organophosphates. The lowest mass loads (mg/day/1000 inhabitants) were found in Utrecht and Oslo. These results were in agreement with several national statistics related to pesticides exposure such as pesticides sales. The daily intake of pyrethroids was estimated in each city and it was found to exceed the acceptable daily intake (ADI) only in one city (Castellon, Spain). This was the first large-scale application of WBE to monitor population exposure to pesticides. The results indicated that WBE can give new information about the “average exposure” of the population to pesticides, and is a useful complementary biomonitoring tool to study population-wide exposure to pesticides

Enantiomeric profiling of chiral illicit drugs in a pan-European study

The aim of this paper is to present the first study on spatial and temporal variation in the enantiomeric profile of chiral drugs in eight European cities. Wastewater-based epidemiology (WBE) and enantioselective analysis were combined to evaluate trends in illicit drug use in the context of their consumption vs direct disposal as well as their synthetic production routes. Spatial variations in amphetamine loads were observed with higher use in Northern European cities. Enantioselective analysis showed a general enrichment of amphetamine with the R-(−)-enantiomer in wastewater indicating its abuse. High loads of racemic methamphetamine were detected in Oslo (EF = 0.49 ± 0.02). This is in contrast to other European cities where S-(+)-methamphetamine was the predominant enantiomer. This indicates different methods of methamphetamine synthesis and/or trafficking routes in Oslo, compared with the other cities tested. An enrichment of MDMA with the R-(−)-enantiomer was observed in European wastewaters indicating MDMA consumption rather than disposal of unused drug. MDA's chiral signature indicated its enrichment with the S-(+)-enantiomer, which confirms its origin from MDMA metabolism in humans. HMMA was also detected at quantifiable concentrations in wastewater and was found to be a suitable biomarker for MDMA consumption. Mephedrone was only detected in wastewater from the United Kingdom with population-normalised loads up to 47.7 mg 1000 people−1 day−1. The enrichment of mephedrone in the R-(+)-enantiomer in wastewater suggests stereoselective metabolism in humans, hence consumption, rather than direct disposal of the drug. The investigation of drug precursors, such as ephedrine, showed that their presence was reasonably ascribed to their medical use