Abstract
The specific compositions of human excreta in sewage can be used as biomarkers to indicate the disease prevalence, health status, and lifestyle of the population living in the investigated catchment. It is important for guiding and evaluating public health policies as well as promoting human health development. Among several parameters of wastewater-based epidemiology (WBE), the decay of biomarkers during transportation in sewer and storage plays a crucial role in the back-calculation of population consumption. In this paper, we summarized the stability data of common biomarkers in storage at different temperatures and in-sewer transportation. Among them, cardiovascular drugs and antidiabetic drugs are very stable which can be used as biomarkers; most of the illicit drugs are stable except for cocaine, heroin, and tetrahydrocannabinol which could be substituted by their metabolites as biomarkers. There are some losses for part of antibiotics and antidepressants even in frozen storage. Rapid detection of contagious viruses is a new challenge for infectious disease control. With the deeper and broader study of biomarkers, it is expected that the reliable application of the WBE will be a useful addition to epidemiological studies.
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Introduction
Based on the analysis of human excretion products (biomarkers) in municipal wastewater, wastewater-based epidemiology (WBE) was proposed to estimate the amount of specific drugs used by the population in a given catchment of a wastewater treatment plant (WWTP) (Daughton 2001). It has been successfully applied to estimate the consumption of illicit drugs (Du et al. 2020a) and therapeutic drugs (van Nuijs et al. 2015). The drug would be lost during the transportation after the excretion from human body to the WWTPs due to hydrolysis, absorption, repartition, and microbial decay. According to the substance balance, the per capita mass load can be back-calculated based on the drug concentration in the influent of the WWTP by Eq. (1) (Zuccato et al. 2008):
where Mc is the daily per capita consumption of the target drug, mg· (day·1000 people)−1; C is the concentration of the drugs measured in the influent, ng·L−1; F is the daily influent flow of the WWTP, L·day−1; P is the population of the area served by the WWTP, 1000 people; S is the stability of drugs, %; E is excretion rate of the drugs, %.
In addition to the back-calculation of drugs consumption, the research of WBE has gradually expanded to other aspects, such as using endogenous (produced naturally in the body) or exogenous metabolites (substances produced by intentional consumption or by accidental exposure) to assess the health status of the population (Gracia-Lor et al. 2017a). Therefore, the drug in Eq. (1) can be collectively referred to as biomarker.
In the WBE study, the uncertainty is the combined results of all parameters in Eq. (1). Among them, F is provided by the operator of WWTP and it is related to the maintenance of the flow meter. As for C and P, there are a lot of studies have been carried out to increase the accuracy of the analysis of compounds (Félix et al. 2016) and population estimation (Rico et al. 2017). Compared to other parameters, there are still many blanks in the study of the human excretion rate of the drugs (E) and their stability (S). A suitable biomarker must meet the following criteria: (1) It must be excreted primarily in urine and the concentration level in urine should be at least in the μg/L level to ensure that it can be detected after dilution by raw sewage (Chen et al. 2014). (2) It must be sufficiently stable in sewage, and substances with low decay (< 20%) are generally considered suitable as biomarkers (McCall et al. 2016; Daughton 2012b). (3) Preferably, it should be specific to human metabolism, ensuring that its presence originates only from human metabolism and not from external emissions (Daughton 2012a). (4) The excretion is consistent across populations (gender, age, ethnicity, etc.). According to the above criteria, some of the easily decay substances (through absorption, hydrolysis, and/or degradation process) are not suitable as biomarkers for back-calculation while their stable metabolite may be an alternative. Thus, a correction factor (CF) is added to revise Eq. (1) as Eq. (2):
where C, S are the parameters for metabolites, and CF is calculated by Eq. (3):
where MWparent drug is the molecular mass of the parent drug; MWmetabolite is the molecular mass of the metabolite; Emetabolite is the excretion rate of the metabolite, %.
In this paper, we summarize the human excretion rates and stability in-sewer and in-sample of biomarkers reflecting drug use, lifestyle, and disease transmission based on the available WBE papers, expecting to lay the foundation for biomarker selection in the application of WBE.
Data sources
The literature search was conducted in the Web of Science database for the period: January 1, 2000–April 2, 2022; search content: subject = (sewage epidemiology) or (wastewater-based epidemiology), literature type = article and review. Papers that reported substance stability data were manually screened and summarized according to their study objects and experimental conditions.
Biomarkers of addictive substances
Illicit drugs
Initially, WBE was used to investigate cocaine use in the community (Zuccato et al. 2005), and has now been well applied to various illicit drugs. We evaluated the storage stability, and stability in-sewer for each substance according to high stability (decay 0–20%), medium stability (decay 20–60%), and low stability (decay 60–100%) (McCall et al. 2016) based on the available papers (Table 1).
Only 1–5% of cocaine entering the body is excreted as prototype, and it is unstable in sewage (Gheorghe et al. 2008), with about 29.2% being excreted as the metabolite benzoylecgonine (BEG) (Ambre et al. 1988). Cocaine consumption is mainly back-calculated through BEG because of its unique source, stability, and qualitative and quantitative match to human urine (Thai et al. 2014). Castiglioni et al. obtained a correction factor (CF) of 3.59 for cocaine by dividing the molecular weight ratio COC/BEG (303/289) by 0.292 (Castiglioni et al. 2013).
The main active ingredient of cannabis is Δ-9-Tetrahydrocannabinol (THC), but it cannot be used as a biomarker for WBE due to its instability in sewage (Heuett et al. 2015). THC-COOH, a metabolite of THC, is highly stable in sewage compared to other metabolites and is therefore used as a biomarker for cannabis consumption (Causanilles et al. 2017). However, cannabis is very extensively metabolized in the human body and the excretion percentage of THC-COOH is only 0.5% with its CF of 182 (Gracia-Lor et al. 2016). In addition, due to the low polarity of THC-COOH, the recovery rate of THC-COOH in the sample after acidification treatment is only 52% (Causanilles et al. 2017). The low excretion and low recovery rate are two difficulties for accurate estimation of cannabis consumption. Future research can be conducted for the screening of more suitable biomarkers or the optimization of sample pretreatment methods.
Opioids are still one type of abused drugs in Europe. Heroin is rapidly hydrolyzed to 6-acetyl morphine (6-MAM) in the body and further hydrolyzed to morphine in the liver (Smith 2009), so 42% of the heroin taken is excreted as morphine and 1.3% as 6-MAM (van Nuijs et al. 2011b). Heroin and 6-MAM are unstable in sewage and sewer (McCall et al. 2016; Thai et al. 2014), and back-calculation based on their concentrations may underestimate heroin consumption. Morphine is highly stable with a CF of 3.1 (Zuccato et al. 2008). However, the amount of morphine produced by therapeutic use and codeine metabolism should be deducted (Du et al. 2019). This poses new challenges to the back-calculation and more studies are needed to find eligible biomarkers for opioids consumption.
Amphetamine-type stimulants (ATS) are the most used stimulants (UNODC 2015), mainly including amphetamine, methamphetamine, and MDMA (3,4-Methylenedioxy-N-methylamphetamine). The three illicit substances currently use the parent compounds as biomarkers, and all are chiral enantiomers. Differences in the metabolic conversion rate of chiral enantiomers change the ratio of enantiomers. So, verifying their chiral characteristics in sewage allows to distinguish between direct disposal and consumer use of the substance (Xu et al. 2017). For example, methamphetamine-producing plants or police raids may result in direct disposal and thus affect the back-calculation result. The two can be effectively distinguished using enantiomeric profifiling, with enantiomeric fractions (EFs) > 0.5 indicating illegal use and EFs equal to 0.5 indicating direct disposal (Eq. 4). However, pure enantiomer will be produced in the synthesis of methamphetamine using ephedrine, at which point enantiomeric profifiling cannot distinguish between processing events. Bade et al. recently found that direct disposal and consumption of methamphetamine could be distinguished when benzidine was used as the biomarker for methamphetamine. Moreover, it showed high stability (decay rate < 20%) for up to 1 week at both 4 °C and 20 °C. They obtained reliable results when they used the method to back-calculate methamphetamine consumption in samples taken from Australian WWTPs (Bade et al. 2021).
Ketamine and methadone are two of the more studied illicit drugs. Although both ketamine and its metabolite nor-ketamine are very stable in sewage (Lin et al. 2021b), ketamine is generally chosen as the biomarker because of its higher concentration and detection frequency in sewage. Du et al. revised the ketamine excretion factor (E = 20%) and the consumption data estimated using the new excretion factor matched better with the official data (Du et al. 2020b). The main metabolite of methadone is EDDP and they both show high stability in sewage (van Nuijs et al. 2012). Five to fifty percent of methadone is excreted in urine as prototype and 27.5% is generally used as the excretion rate (Postigo et al. 2011); the excretion rate of EDDP is 55% (Thai et al. 2016) and CF is 2.04 (Zheng et al. 2021). It has been reported that methadone is completely undetectable after 72 h at 4 °C (González-Mariño et al. 2010). So, it is more appropriate to use EDDP as biomarker for drug consumption back-calculation based on the current study.
New psychoactive substances
New psychoactive substances (NPS) are substances that are not controlled by the Convention on Psychotropic Substances of 1971 but are abused and can pose a threat to public health (UNODC 2013). These substances are produced by slightly altering the functional groups of controlled substances (e.g., cocaine, amphetamines) and have psychoactive effects as traditional drugs. Over the past few years, sales of NPS in the illicit drug market have grown rapidly, and new categories continue to emerge. Their high toxicity and adverse health effects have raised concerns because some death cases were reported (Krotulski et al. 2018), and its consumption estimation is gradually being carried out.
The prevalence of NPS and the detected concentrations in sewage are low (pg·L−1-ng·L−1) compared to other illicit drugs due to a large number of species and constant new synthesis (Bijlsma et al. 2020). Synthetic cathinones and phenethylamines are the two main types of NPS that are used more frequently. Among them, methcathinone, mephedrone, and methylone were the substances detected more frequently in Europe in the past 2 years (Castiglioni et al. 2021). In 2017–2018, the most detected in Australia were pentylone, N-ethylpentanone, and ethylone, and the popular substances in 2019–2020 became eutylone, mephedrone, and methylone (Bade et al. 2020). The current studies on NPS focus on qualitative determinations using parent compounds as biomarkers to detect temporal differences in prevalence across regions and determine potential outbreaks in their use. However, the lack of pharmacokinetic data and drug stability data in the sewer and sewage may hinder accurate back-calculation of NPS drug consumption. We summarize the decay of some NPS biomarkers in different states (in Table 2), which are stable substances and are used for reliable results of consumption back-calculation.
Drugs for common diseases or exogenous biomarkers
The effectiveness of community health programs, which play an important role in public health, depends on routine monitoring and assessment of the health status of community populations, and the current challenge is mainly the timeliness and reliability of the assessments. Exogenous biomarkers refer to specific classes of drugs, such as antibiotics, antidepressants, and β-blockers, which are mainly used in the treatment of specific diseases.
Antibiotics
The antibiotics can be classified into macrolides, tetracyclines, fluoroquinolones, quinolones, penicillins, cephalosporines, lincosamides, sulfonamides, and nitroimidazoles according to their chemical structures. Parent compounds are now commonly used as biomarkers for the detection of antibiotics. Among them, penicillins, cephalosporins, sulfonamides, nitroimidazoles, and lincosamides are considered relatively stable (decay < 20% after 3 months of storage at − 20 °C); In contrast, fluoroquinolones, quinolones, tetracyclines, and macrolides are unstable (Llorca et al. 2014). It was reported that the metabolites of sulfapyridine, sulfamethoxazole, trimethoprim, and azithromycin were stable (decay < 20%) in sewage at 4 °C (48 h) and − 20 °C (30 days) (Han et al. 2021).
However, the assessment of the consumption of antibiotics has significant limitations. In addition to the therapeutic use by humans, a large portion of the antibiotics in sewage originates from the sewage discharges from pharmaceutical plants and breeding. It was reported that about one-third of unused antibiotics were disposed directly in landfills (Zhang et al. 2020) and the antibiotics may enter the WWTPs with the landfill leachate (Yu et al. 2020), leading to an overestimation of human antibiotic consumption. The stability of antibiotics and their metabolites in-sewer is also unknown, and more relevant studies are needed to propose more targeted human’s biomarkers to improve the accuracy of antibiotic consumption estimation.
Antidepressants
Major depressive disorder (MDD) is the 11th most important factor in disability-adjusted life years globally (Murray et al. 2012). Selective 5-HT reuptake inhibitors (SSRIs) are commonly prescribed antidepressants, including fluoxetine (FLU), sertraline (SER), paroxetine (PAR), and citalopram (CTP). Another class of antidepressants are selective 5-hydroxytryptamine and norepinephrine reuptake inhibitors (SSNRIs), represented by venlafaxine (VEN). These antidepressants have been widely marketed since the mid-1980s, mainly for patients diagnosed with clinical depression (Schultz and Furlong 2008).
Lin et al. investigated the stability of antidepressants in sewage and sewer under different conditions. It was found that VEN, FLU, and CTP showed high stability after 72 h at 4–35 °C (Table 3). The biodegradation rates of PAR and SER increased with temperature, with decay rates of about 26% and 36% at 35 °C, respectively, and were medium stable substances. When the temperature was below 15 °C, the decay of drugs was mainly due to the adsorption of suspended solids (SS), and their adsorption basically followed the Kow order, indicating that Kow can be used to predict the adsorption of SS on antidepressants. The decay rates of VEN, FLU, and CTP in the aerobic and anaerobic sewer with biofilms ranged from 20 to 60% after 24 h. They are medium-stable substances and can be used as biomarkers of WBE within a certain range. While PAR and SER decayed > 80% (Lin et al. 2021a), they are low stable substances with large errors in back-calculation and are not suitable as biomarkers for WBE.
WBE can be an important tool for assessing the mental health of the population, but in developing areas where people often do not seek treatment because of the lack of understanding of mental health problems or forced by economic and social pressures. Thus, back-calculating drug consumption to determine the mental health of the area may lead to optimistic results.
Sedative and hypnotic drugs
Benzodiazepines are commonly prescribed psychotropic drugs used to treat various psychiatric disorders such as anxiety, stress, and insomnia. However, they have a high dependence potential and are frequently abused (Richard et al. 2020), which have been detected in ng L−1 levels in sewage (Asimakopoulos and Kannan 2016). Since many benzodiazepines share common metabolites (for example, oxazepam is a metabolite of temazepam and diazepam) (Griffin et al. 2013), the parent compound is mainly used as biomarker. Although clonazepam and flunitrazepam decayed < 20% in sewage after 24 h, their metabolites, 7-aminoclonazepam, and 7-aminoflunitrazepam, are more stable (decay rates < 5%) (Table 3). Therefore, it is more appropriate to use their metabolites as biomarkers (Liu et al. 2022; Racamonde et al. 2014). The excretion rate of 7-aminoflunitrazepam is about 90% and CF is 0.81 (Shu et al. 2021).
Currently, most of the research on benzodiazepines is limited to the detection of drugs, and only a few drugs have reported stability data (Liu et al. 2022). The link between drug use levels and population health has not been established, so more research is needed to promote the use of WBE for this class of drugs.
Cardiovascular drugs
Cardiovascular diseases are common in middle-aged and elderly people over 50 years old, with high prevalence, disability rate, and mortality rate, and ranking the first among various causes of death (McAloon et al. 2016). In recent years, cardiovascular diseases are trending younger due to obesity and unbalanced diets, so the use of WBE to monitor the use of cardiovascular drugs in specific regions is important to understand the health level of the population.
One of the more used classes of drugs is the β-adrenergic receptor blockers (β-blockers), such as atenolol, metoprolol, nadolol, and propranolol, the parent compound is now mostly used as biomarker. Ninety-two percent of atenolol is excreted in the urine as prototype, whereas propranolol is almost completely absorbed in humans and only 0.5% is excreted in the urine as prototype (Thomaidis et al. 2016). Metabolism of metoprolol is similar to it, with 5% excreted as prototype (Alder et al. 2010). Typical cardiovascular drugs (metoprolol, bezafibrate, gemfibrozil, and atenolol) are highly stable in sewage and sewer (Lin et al. 2021a) (Table 3), and therefore they are considered suitable biomarkers for WBE.
Antidiabetic drugs
Diabetes has serious complications, such as stroke, heart disease, kidney disease, peripheral artery disease, and vision impairment. Its prevalence has been increasing worldwide over the past decades (Rafael et al. 2013), and therefore the prevalence of diabetes needs to be continuously monitored to reflect the health status of the population. Metformin is a synthetic antidiabetic drug with no natural origin or known analogs (Yao et al. 2018) and is the most widely used drug in the treatment of diabetes (Viollet et al. 2012). It is not metabolized in humans and is mainly excreted in urine and feces (80%), with high stability in both sewage and sewer (Lin et al. 2021a; Yan et al. 2019) (Table 3), and thus meets the criteria for biomarker. In addition, glipizide is one of the most widely used oral antidiabetic drugs. It is rapidly absorbed in the intestine and metabolized by the liver, and about 97% is excreted in the urine. Glipizide exhibits high stability in both sewage and sewer from 4 to 35 °C (Lin et al. 2021a) and meets the criteria of biomarker that can be used as a complement to metformin to jointly assess the prevalence of diabetes.
Asthma drugs and antihistamines
The global prevalence of asthma and allergic rhinitis is increasing, with children and young adults being the most prevalent groups (Pawankar 2014). Detecting the prevalence of asthma and allergy in the population and discovering its relationship with specific environmental factors are new applications of WBE. The three common antihistamines loratadine, fexofenadine, and cetirizine, as well as the asthma drugs salbutamol and salmeterol, are excreted in the urine after administration. And their consumption is now mainly back-calculated using the parent drug as biomarker (Choi et al. 2018; Liu et al. 2022). The decay rate of salbutamol is < 20% after 24 h in sewage and sewer (Table 3), which is a highly stable substance. While salmeterol is stable in sewage, its decay rate in the aerobic sewer is > 40% (Lin et al. 2021a), making it a medium stable substance and therefore salbutamol is more suitable as a biomarker for asthma drugs. Loratadine and its metabolite desloratadine are unstable (decay rate > 50%) in sewage and sewer. Cetirizine is stable in sewage (decay rate < 20% after 72 h at room temperature), but decayed > 20% in aerobic sewer. Whereas, Fexofenadine is stable in both sewage and sewer with a decay rate < 20% (Table 3) (Fedorova et al. 2014; Liu et al. 2022), making it more suitable as biomarker for antihistamines. In addition to this, more asthma, allergy, and other respiratory medications should be detected, as consumers may use many different medications based on need and preference.
Anticancer drugs
Cancer is now considered to pose a serious threat to global development and according to surveys globally, the chances of developing cancer during the lifetime (0–79 years) are 1 in 3 for men and 1 in 4 for women (Rafael et al. 2013). Due to the increased use of various anticancer drugs, they were also frequently detected in sewage (ng/L) (Victoria et al. 2014). Most anticancer drugs are structurally stable to maximize their reach to the part of the body that needs treatment. Hence, they are highly chemically stable (Janssens et al. 2019) and not biodegradable (Kummerer et al. 1997).
However, data on stability studies in sewer and sewage are not yet available. The main source of anticancer drugs in sewage is excretion by patients, so suitable anticancer drugs should be selected as biomarkers for the assessment of the prevalence of different types of cancer in a specific regional population.
Endogenous biomarkers
Endogenous compounds are associated with human metabolism and can avoid the problems of exogenous compounds, e.g., differentiating the origin of substances in sewage, when used as biomarkers. However, their main limitation is the intra and inter individually excessive variability in excretion. Creatinine, 5-HIAA, cortisol, androstenedione, and isoprostane are currently the main endogenous biomarkers used for population assessment and oxidative stress levels.
Creatinine is a decomposed product of creatine phosphate in muscle and is usually produced at a constant rate. But it is unstable in sewage (Rico et al. 2017) (Table 4) and cannot be used as a biomarker. 5-HIAA, cortisol, and androstenedione have been reported to have high urinary excretion rates and are therefore considered to have potential as population biomarkers. However, cortisol and androstenedione are unstable in sewer, whereas 5-HIAA exhibits high stability (Thai et al. 2019), with a level of approximately 3.44 mg·(day·person) −1 in urine (Tisha et al. 2008), therefore is the most promising biomarker available. The potential of catecholamine metabolites—homovanillic acid (HVA) and vanillylmandelic acid (VMA)—as biomarkers were recently evaluated and both were found to be stable in sewage, with < 20% decay after 14 days of storage at − 20 and 4 °C. Their excretion factors are 1.24 ± 0.07 and 1.07 ± 0.05 mg·(day·person) −1 for HVA and VMA, respectively, and are suitable for monitoring relative population size changes in the short term (Pandopulos et al. 2021).
8-iso-prostaglandin F2α (8-iso-PGF2α) and prostaglandin E2 (PGE2), which are associated with oxidative stress, are stable in sewage and sewer (O’Brien et al. 2019; Ryu et al. 2015), and thus may serve as reliable biomarkers of oxidative stress in the community.
Pathogens
Monitoring the presence of pathogens in sewage from entire communities is important for preventing the spread of infectious diseases. The use of WBE for this detection is an emerging field that shows more potential with the rapid development of technologies such as high-throughput sequencing and bioinformatics.
Conventional pathogens
Human enteroviruses are responsible for many stomachs and intestinal infections, respiratory infections, conjunctivitis, hepatitis, and other serious infectious agents with high mortality rates in immunocompromised individuals. Patients with viral gastroenteritis or viral hepatitis excrete approximately 105 to 1011 viral particles/g stool (Bosch 1998), including adenovirus, astrovirus, norovirus, hepatitis E virus, and enterovirus. Therefore, routine monitoring of pathogenic enteroviruses in sewage is important to understand the abundance and transmission of viruses in a certain area. It provides valid information for the development and evaluation of health intervention programs.
Enteroviruses can survive over a wide pH range (pH 3–10) and at low temperatures for 4–6 months (Kocwa-Haluch 2001). Moreover, due to their host-specific requirements (infecting only humans), they have no regenerative capacity in the environment and can be used to assess the risk of virus transmission (Fong and Lipp 2005). For example, high concentrations of the virus were detected in sewage during norovirus outbreaks (5 × 103–2 × 104 copies·mL−1) (Thongprachum et al. 2018). The sewage analysis has proved to be a very sensitive method for monitoring poliovirus transportation (Ivanova et al. 2019), with a detection limit of 20 CCID50 (Delogu et al. 2018), can help track wild and vaccine-derived poliovirus, and has played a major role in the global elimination of poliovirus.
In the follow-up of eight pathogenic viruses (norovirus, astrovirus, astrovirus, rotavirus, adenovirus, Aichi virus, paralysis virus, hepatitis A virus, and hepatitis E virus) in sewage, it was found that Ct thresholds of 24.3–45 for viruses could be used as an early warning of outbreaks (Hellmér et al. 2014).
SARS-CoV-2
The recent outbreak of corona virus disease 2019 (COVID-19) has become a global public health event, with the number of infections continuing to increase in many countries, causing unprecedented harm to human health and safety. Several recent studies have demonstrated the presence of live SARS-CoV-2 in the stool and urine of both symptomatic and asymptomatic populations (Jeong et al. 2020; Xiao et al. 2020). In addition, viral RNA continued to be detected in stool, rectal swabs, and urine for 5 weeks after patients tested negative for respiratory samples and resolution of symptoms (Ling et al. 2020; Xu et al. 2020), and survived for 4 days in urine, but only 2 days in the stool (Liu et al. 2021).
The steps to detect SARS-CoV-2 RNA concentration in sewage include virus concentration, extraction, and quantification using RT-qPCR (Kumblathan et al. 2021). However, SARS-CoV-2 RNA may be broken down into smaller fragments during sewer transportation as well as in sewage, so there is a large uncertainty for the detection of viral RNA in sewage. Boogaerts et al. tested the stability of N2 and E gene fragments and found that after 10 days of storage in 4 °C sewage, the N2 gene showed high stability and the E gene was relatively less stable (Boogaerts et al. 2021a); However, Hokajärvi et al. experimentally found that the E gene remained stable after 84 days of storage in sewage at 4 °C (Hokajärvi et al. 2021). The results of current studies on viral RNA stability are highly variable, so more studies on viral RNA stability under standardized and uniform conditions are needed. Additionally, the viral RNA load in sewage is substantially reduced in the -20 °C storage (Boogaerts et al. 2021a), so sewage samples should be transported and stored at 4 °C to reduce the decay of viral RNA. More studies are also needed to explore the effects of sewer transportation on viral RNA.
Studies have shown that the slow decay of SARS-CoV-2 RNA in sewage supports its detection and quantification, with detection limits of 3.99, 5.52, and 5.74 copies/L for E gene, RNA, and N gene, respectively (Monteiro et al. 2022), which can be used as a feasible tool to monitor the presence of the virus in the community. Currently, most of the diagnostic criteria for positive novel coronaviruses worldwide are Ct values ≤ 35. There are no criteria for determining whether there is an outbreak from the concentration of virus in sewage, and more research is needed to propose uniform criteria to enable WBE to better monitor the development of the outbreak.
Other applications of biomarkers
Exogenous biomarkers to back-calculate population size
In addition to assessing the use of illicit substances and common drugs, some biomarkers are stable and have low fluctuations in per capita emissions that can be used to assess the size of the population in the investigated area, and Eq. (5) is obtained by deforming Eq. (1)
where C is the biomarker concentration, ng·L−1; F is the daily flow rate of the WWTP, L·day−1; and DDD is the daily dose required per 1000 inh, mg· (day·1000 people) −1; E is the excretion rate, %.
The artificial sweetener acesulfame (ACE) is not metabolized in humans and is completely excreted after consumption with a DDD of 0.057 mg· (day·1000 people) −1 (Rico et al. 2017). ACE is highly stable (decay < 20%) in sewage and sewer (Lin et al. 2021b; O’Brien et al. 2019) and has therefore been proposed as a potential biomarker. Fourteen exogenous compounds, including atenolol, carbamazepine, codeine, norfloxacin, and paracetamol, were quite reliable because of their strong correlation between population and mass load (R2 > 0.8) (O’Brien et al. 2014). They can be used as potential biomarkers for population estimation, but the respective mass loadings within different regions or at different population sizes need to be obtained based on specific consumption characteristics.
Exogenous markers to assess population lifestyle habits
Alcohol
After consumption of alcohol-containing beverages, 95–98% of ethanol is metabolized primarily in the liver, where ethanol is first converted to acetaldehyde, further oxidized to acetic acid, and the rest is excreted through urine, breathing, and sweat (Jones 1990). Ethyl sulfate (EtS) and ethyl glucuronide (EtG) can be detected in urine 1 h after alcohol ingestion (Helander and Beck 2005) and they are good indicators of alcohol consumption. Among them, EtG is less stable in sewage and sewer (Banks et al. 2018) (Table 5), while EtS shows high stability and originates only from the human metabolism of alcohol. It is therefore considered as the best biomarker for estimating alcohol consumption (López-García et al. 2020). Thai et al. obtained a CF of 4000 by directly comparing alcohol sales data with EtS concentrations measured in sewage (Thai et al. 2021), overcoming the low excretion rate of EtS (0.010–0.016%) (Reid et al. 2011) and effectively improving the accuracy of alcohol consumption estimates for the Australian population. However, the use of the CF in different regions will bring uncertainty due to the large variation in the excretion rate of EtS in the population and the different levels of decay of EtS in different sewers.
Tobacco
Nicotine, the main alkaloid in tobacco, is addictive and is the main reason for the continued use of tobacco products (Hukkanen et al. 2005). Nicotine is extensively metabolized in humans and excreted in the urine as parent and metabolites (mainly cotinine and trans-3′-hydroxycotinine). All three compounds show high stability in sewers and sewage (Castiglioni et al. 2014) (Table 5), so they can be used as biomarkers for the back-calculation of tobacco consumption. From the available literature, we determined the mean percentage excretion of cotinine and trans-3′-hydroxycotinine after nicotine absorption (Benowitz and Jacob 1994; Jacob et al. 1988) (Table 6). Since more than 90% of the conjugated form of the metabolite can be converted to the free state by β-glucuronidase in sewage (Rodríguez-Álvarez et al. 2014), the CF is calculated to be 3.13 and 2.31 using 30% and 44% as the excretion rates of cotinine and trans-3′-hydroxycotinine, respectively (Boogaerts et al. 2021b).
It is noted that the use of teas, nicotine replacement therapies (NRTs), and e-cigarettes also excrete nicotine and may lead to an overestimation of tobacco consumption. Two specific biomarkers of tobacco, anabasine, and anatabine, are found stable in sewage (Tscharke et al. 2016) and can be used as biomarkers of tobacco consumption (Zheng et al. 2020). However, information on excretion rates for anabasine and anatabine is not available and only mass load changes can be used to assess tobacco use.
Caffeine
Caffeine is the most widely used stimulant in the world and is widely found in a variety of teas, energy drinks, coffee, and some medications, but coffee is its primary source. Caffeine is extensively metabolized in the liver, with 1.7% of caffeine excreted in the urine as prototype and the rest as metabolites: 3,7-dimethylxanthine (1.5%), 1,7-dimethylxanthine (4.6%), and 1,3-dimethylxanthine (0.6%), further decomposition to 1,7-dimethyl uric acid (6.7%) (Heckman et al. 2010). By comparing the metabolic profiles of each metabolite in sewage and urine, only 1,7-dimethyluric acid was found to be a suitable biomarker with a CF of 14.8 (Gracia-Lor et al. 2017b).
Other foods
Some specific foods are also used as biomarkers to assess the standard of living of the population in a given area. N-methyl-2-pyridone-5-carboxamide (2PY) and N-methyl-4-pyridone-3-carboxamides (4PY) are the major metabolites of vitamin B3 (Tsuji et al. 2011). α-carboxyethyl-hydroxychromans (α-CEHC) is the main metabolite of vitamin E (Lodge et al. 2001). 4-Pyridoxic acid accounts for 40–60% of dietary vitamin B6 intake and is a marker of short-term vitamin B6 intake (Tsuji et al. 2010). There is a dose-dependent relationship between citrus consumption and urinary excretion of proline betaine (Lang et al. 2017). Enterodiol and enterolactone are abundant in cereals, legumes, and fruits (Potischman and Freudenheim 2003). Therefore, these substances are considered appropriate biomarkers for a healthy diet. Vitamin B, cereals, fruits and vegetables, and other high-fiber foods were found to be positively associated with higher socioeconomic status. The correlation between α-CEHC and sociodemographic indicators was not significant, which may be because the prevalence of vitamin E in readily available foods (e.g., cooking oils) (Choi et al. 2019). However, the data on the stability of these biomarkers in sewer and sewage are not available yet, so it is unable to analyze the quantitative consumption characteristics of these substances and only qualitative analysis can be performed.
Conclusion and prospect
Conclusions
Municipal sewage is a reservoir of biological and chemical information that reflects the health status of populations. Through the detection of relevant biomarkers, WBE can provide a range of information about the dietary consumption and health of the population. Importantly, as an emerging subject, the capabilities of WBE are rapidly expanding as detection methods and technologies improvement. It can also be used as a tool to detect human exposure to emerging contaminants.
As we discussed previously, with information on biomarker excretion, sewage and in-sewer conversion, WBE has the potential to provide information on illicit and therapeutic drugs consumption, and other health aspects of the population. The main conclusions obtained in this paper are as follows:
-
(1)
Most of the illicit drugs showed high stability in sewage and sewer, only cocaine, heroin, and THC are unstable and their stable metabolites BEG, morphine, and THC-COOH are used as biomarkers for consumption back-calculation, respectively.
-
(2)
Among the common drugs, the cardiovascular drugs metoprolol, bezafibrate, gemfibrozil, atenolol, and the antidiabetic drugs metformin are stable in sewage and sewer and can accurately back-calculate the per capita consumption of drugs by WBE.
-
(3)
Other common drugs such as antibiotics and antidepressants are degraded to some extent in both sewage and sewer, which may have large errors in back-calculation and require more reliable biomarkers.
-
(4)
For alcohol, tobacco, and caffeine, reliable biomarkers have also been found as EtS, nicotine, cotinine, trans-3′-hydroxycotinine, and 1,7-dimethyluric acid, respectively.
-
(5)
Acidification (except THC-COOH) and low temperature (− 20–4 °C) are effective in the long-term storage of samples. But for some drugs such as sulfonamides and macrolactone antibiotics, the stability is significantly reduced after a week of frozen storage. For benzodiazepines, acidification can also significantly reduce the stability of the drug, and it is recommended to use sodium metabisulfite (0.5 g/L) to preserve sewage samples (the drug can be stable at − 20 °C, 4 °C, and room temperature for 1 week) and analyze them as soon as possible.
Prospect
For the better application of WBE in various fields, some suggestions for the needs and trends in its development are presented here:
-
(1)
Enhancement of human pharmacokinetic studies. The selection of biomarkers that are excreted mainly through urine and metabolized in high proportions is essential for the back-calculation of substance consumption. And it helps to distinguish the number of substances from human or other sources.
-
(2)
Stability studies of substances within samples and in the sewer need to be refined. Stability studies have been conducted for more studied substances such as cocaine, cannabis, venlafaxine, and metformin, but stability studies have yet to be conducted for more drugs. In addition, the stability data reported in available studies for the same substance vary greatly due to different experimental conditions and the number of microorganisms in sewers in different regions. So, there is a need to establish uniform and standardized stability experimental conditions to produce accurate data.
-
(3)
Regular virus monitoring of sewage using DNA-based biosensors may provide an early warning of an impending outbreak. Molecular biology techniques also play an important role in the development and application of endogenous biomarker analysis and virus monitoring in WBE.
In the future, more biomarkers that can reflect human diet and health need to be explored to provide a more direct measure of population health. At the same time, the relationship between WBE detection and socio-economic or environmental indicators should be explored and established, so that it can show more application value for public health. The development of WBE would rely on the development of analytical and detection technologies, such as mass spectrometry and metabolomics technologies. More research is also needed on biomarkers’ pharmacokinetics, sewer migration transformation, and stability in sewage, which are key information for translating measurements in sewage into population-level consumption values.
Data availability
The authors ensure that all data, materials, software applications, and custom code support the statements published in this study.
References
Alder AC, Schaffner C, Majewsky M et al (2010) Fate of β-blocker human pharmaceuticals in surface water: comparison of measured and simulated concentrations in the Glatt Valley Watershed, Switzerland. Water Res 44:936–948. https://doi.org/10.1016/j.watres.2009.10.002
Ambre J, Ruo TI, Nelson J et al (1988) Urinary excretion of cocaine, benzoylecgonine, and ecgonine methyl ester in humans. J Anal Toxicol 12:301. https://doi.org/10.1093/jat/8.1.23
Asimakopoulos AG, Kannan K (2016) Neuropsychiatric pharmaceuticals and illicit drugs in wastewater treatment plants: A review. Environ Chem 13:541. https://doi.org/10.1071/EN15202
Bade R, Abdelaziz A, Nguyen L et al (2020) Determination of 21 synthetic cathinones, phenethylamines, amphetamines and opioids in influent wastewater using liquid chromatography coupled to tandem mass spectrometry. Talanta 208:120479. https://doi.org/10.1016/j.talanta.2019.120479
Bade R, Ghetia M, Chappell A et al (2021) Pholedrine is a marker of direct disposal of methamphetamine. Sci Total Environ 782:146839. https://doi.org/10.1016/j.scitotenv.2021.146839
Baker DR, Kasprzyk-Hordern B (2011) Critical evaluation of methodology commonly used in sample collection, storage and preparation for the analysis of pharmaceuticals and illicit drugs in surface water and wastewater by solid phase extraction and liquid chromatography–mass spectrometry. J Chromatogr A 1218:8036–8059. https://doi.org/10.1016/j.chroma.2011.09.012
Banks APW, Lai FY, Mueller JF et al (2018) Potential impact of the sewer system on the applicability of alcohol and tobacco biomarkers in wastewater-based epidemiology. Drug Test Anal 10:530–538. https://doi.org/10.1002/dta.2246
Benowitz NL, Jacob PR (1994) Metabolism of nicotine to cotinine studied by a dual stable isotope method. Clin Pharmacol Ther 56:483–493. https://doi.org/10.1038/clpt.1994.169
Bijlsma L, Celma A, Castiglioni S et al (2020) Monitoring psychoactive substance use at six european festivals through wastewater and pooled urine analysis. Sci Total Environ 725:138376. https://doi.org/10.1016/j.scitotenv.2020.138376
Boogaerts T, Jacobs L, De Roeck N et al (2021a) An alternative approach for bioanalytical assay optimization for wastewater-based epidemiology of SARS-cov-2. Sci Total Environ 789:148043. https://doi.org/10.1016/j.scitotenv.2021.148043
Boogaerts T, Jurgelaitiene L, Dumitrascu C et al (2021b) Application of wastewater-based epidemiology to investigate stimulant drug, alcohol and tobacco use in lithuanian communities. Sci Total Environ 777:145914. https://doi.org/10.1016/j.scitotenv.2021.145914
Bosch A (1998) Human enteric viruses in the water environment: A mini review. Int Microbiol 191–196:10943359
Castiglioni S, Bijlsma L, Covaci A et al (2013) Evaluation of uncertainties associated with the determination of community drug use through the measurement of sewage drug biomarkers. Environ Sci Technol 47:1452–1460. https://doi.org/10.1021/es302722f
Castiglioni S, Senta I, Borsotti A et al (2014) A novel approach for monitoring tobacco use in local communities by wastewater analysis. Tob Control 24:38–42. https://doi.org/10.1136/tobaccocontrol-2014-051553
Castiglioni S, Salgueiro-González N, Bijlsma L et al (2021) New psychoactive substances in several european populations assessed by wastewater-based epidemiology. Water Res 195:116983. https://doi.org/10.1016/j.watres.2021.116983
Causanilles A, Baz-Lomba JA, Burgard DA et al (2017) Improving wastewater-based epidemiology to estimate cannabis use: Focus on the initial aspects of the analytical procedure. Anal Chim Acta 988:27–33. https://doi.org/10.1016/j.aca.2017.08.011
Chen C, Kostakis C, Gerber JP et al (2014) Towards finding a population biomarker for wastewater epidemiology studies. Sci Total Environ 487:621–628. https://doi.org/10.1016/j.scitotenv.2013.11.075
Choi PM, O’Brien JW, Li J et al (2018) Population histamine burden assessed using wastewater-based epidemiology: The association of 1,4-methylimidazole acetic acid and fexofenadine. Environ Int 120:172–180. https://doi.org/10.1016/j.envint.2018.08.009
Choi PM, Tscharke B, Samanipour S et al (2019) Social, demographic, and economic correlates of food and chemical consumption measured by wastewater-based epidemiology. PNAS 116:21864–21873. https://doi.org/10.1073/pnas.1910242116
Daughton CG (2001) Illicit drugs in municipal sewage: Proposed new non-intrusive tool to heighten public awareness of societal use of illicit/abused drugs and their potential for ecological consequences. American Chemical Society, Washington, DC
Daughton CG (2012a) Real-time estimation of small-area populations with human biomarkers in sewage. Sci Total Environ 414:6–21. https://doi.org/10.1016/j.scitotenv.2011.11.015
Daughton CG (2012b) Using biomarkers in sewage to monitor community-wide human health: isoprostanes as conceptual prototype. Sci Total Environ 424:16–38. https://doi.org/10.1016/j.scitotenv.2012.02.038
Delogu R, Battistone A, Buttinelli G et al (2018) Poliovirus and other enteroviruses from environmental surveillance in Italy, 2009–2015. Food Environ Virol 10:333–342. https://doi.org/10.1007/s12560-018-9350-8
Du P, Thai PK, Bai Y et al (2019) Monitoring consumption of methadone and heroin in major chinese cities by wastewater-based epidemiology. Drug Alcohol Depen 205:107532. https://doi.org/10.1016/j.drugalcdep.2019.06.034
Du P, Liu X, Zhong G et al (2020a) Monitoring consumption of common iillicit drugs in Kuala Lumpur, Malaysia, by wastewater-cased epidemiology. Int J Env Res Pub He 17:889. https://doi.org/10.3390/ijerph17030889
Du P, Zheng Q, Thomas KV et al (2020b) A revised excretion factor for estimating ketamine consumption by wastewater-based epidemiology – utilising wastewater and seizure data. Environ Int 138:105645. https://doi.org/10.1016/j.envint.2020.105645
Fedorova G, Golovko O, Randak T et al (2014) Storage effect on the analysis of pharmaceuticals and personal care products in wastewater. Chemosphere 111:55–60. https://doi.org/10.1016/j.chemosphere.2014.02.067
Félix H, Castiglioni S, Covaci A et al (2016) Mass spectrometric strategies for the investigation of biomarkers of illicit drug use in wastewater. Mass Spectrom Rev 3:258–280. https://doi.org/10.1002/mas.21525
Fong T, Lipp EK (2005) Enteric viruses of humans and animals in aquatic environments: Health risks, detection, and potential water quality assessment tools. Microbiol Mol Biol Revs 69:357–371. https://doi.org/10.1128/MMBR.69.2.357
Gao J, Banks A, Li J et al (2017) Evaluation of in-sewer transformation of selected illicit drugs and pharmaceutical biomarkers. Sci Total Environ 609:1172–1181. https://doi.org/10.1016/j.scitotenv.2017.07.231
Gao J, Li J, Jiang G et al (2019) Systematic evaluation of biomarker stability in pilot scale sewer pipes. Water Res 151:447–455. https://doi.org/10.1016/j.watres.2018.12.032
Gheorghe A, van Nuijs A, Pecceu B et al (2008) Analysis of cocaine and its principal metabolites in waste and surface water using solid-phase extraction and liquid chromatography–ion trap tandem mass spectrometry. Anal Bioanal Chem 391:1309–1319. https://doi.org/10.1007/s00216-007-1754-5
González-Mariño I, Quintana JB, Rodríguez I et al (2010) Determination of drugs of abuse in water by solid-phase extraction, derivatisation and gas chromatography–ion trap-tandem mass spectrometry. J Chromatogr A 1217:1748–1760. https://doi.org/10.1016/j.chroma.2010.01.046
Gracia-Lor E, Zuccato E, Castiglioni S (2016) Refining correction factors for back-calculation of illicit drug use. Sci Total Environ 573:1648–1659. https://doi.org/10.1016/j.scitotenv.2016.09.179
Gracia-Lor E, Castiglioni S, Bade R et al (2017a) Measuring biomarkers in wastewater as a new source of epidemiological information: current state and future perspectives. Environ Int 99:131–150. https://doi.org/10.1016/j.envint.2016.12.016
Gracia-Lor E, Rousis NI, Zuccato E et al (2017b) Estimation of caffeine intake from analysis of caffeine metabolites in wastewater. Sci Total Environ 609:1582–1588. https://doi.org/10.1016/j.scitotenv.2017.07.258
Griffin CR, Kaye AM, Bueno FR et al (2013) Benzodiazepine pharmacology and central nervous system-mediated effects. Ochsner J 13:214–223
Han S, Li X, Huang H et al (2021) Simultaneous determination of seven antibiotics and five of their metabolites in municipal wastewater and evaluation of their stability under laboratory conditions. Int J Env Res Pub He 18:10640. https://doi.org/10.3390/ijerph182010640
Heckman MA, Weil J, de Mejia EG (2010) Caffeine (1, 3, 7-trimethylxanthine) in foods: A comprehensive review on consumption, functionality, safety, and regulatory matters. J Food Sci 75:R77–R87. https://doi.org/10.1111/j.1750-3841.2010.01561.x
Helander A, Beck O (2005) Ethyl sulfate: A metabolite of ethanol in humans and a potential biomarker of acute alcohol intake. J Anal Toxicol 29:270–274. https://doi.org/10.1093/jat/29.5.270
Hellmér M, Paxéus N, Magnius L et al (2014) Detection of pathogenic viruses in sewage provided early warnings of Hepatitis A virus and Norovirus outbreaks. Appl Environ Microb 80:6771–6781. https://doi.org/10.1128/AEM.01981-14
Heuett NV, Ramirez CE, Fernandez A et al (2015) Analysis of drugs of abuse by online SPE-LC high resolution mass spectrometry: Communal assessment of consumption. Sci Total Environ 511:319–330. https://doi.org/10.1016/j.scitotenv.2014.12.043
Hokajärvi A, Rytkönen A, Tiwari A et al (2021) The detection and stability of the SARS-cov-2 RNA biomarkers in wastewater influent in Helsinki, Finland. Sci Total Environ 770:145274. https://doi.org/10.1016/j.scitotenv.2021.145274
Hukkanen J, Jacob P, Benowitz NL (2005) Metabolism and disposition kinetics of nicotine. Pharmacol Rev 57:79–115. https://doi.org/10.1124/pr.57.1.3
Ivanova OE, Yarmolskaya MS, Eremeeva TP et al (2019) Environmental surveillance for poliovirus and other enteroviruses: Long-term experience in moscow, russian federation, 2004–2017. Viruses 11:424. https://doi.org/10.3390/v11050424
Jacob RP, Benowitz NL, Shulgin AT (1988) Recent studies of nicotine metabolism in humans. Pharmacol Biochem Be 30:249. https://doi.org/10.1016/0091-3057(88)90453-4
Janssens R, Cristovao MB, Bronze MR et al (2019) Coupling of nanofiltration and UV, UV/TiO2 and UV/H2O2 processes for the removal of anti-cancer drugs from real secondary wastewater effluent. J Environ Chem Eng 7:103351. https://doi.org/10.1016/j.jece.2019.103351
Jeong HW, Kim S, Kim H et al (2020) Viable SARS-CoV-2 in various specimens from COVID-19 patients. Clin Microbiol Infec 26:1520–1524. https://doi.org/10.1016/j.cmi.2020.07.020
Jones AW (1990) Excretion of alcohol in urine and diuresis in healthy men in relation to their age, the dose administered and the time after drinking. Forensic Sci Int 45:217–224. https://doi.org/10.1016/0379-0738(90)90177-z
Kinyua J, Negreira N, McCall A et al (2018) Investigating in-sewer transformation products formed from synthetic cathinones and phenethylamines using liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. Sci Total Environ 634:331–340. https://doi.org/10.1016/j.scitotenv.2018.03.253
Kocwa-Haluch R (2001) Waterborne enteroviruses as a hazard for human health. Pol J Environ Stud 10:485–487
Krotulski AJ, Papsun DM, De Martinis BS et al (2018) N-Ethyl Pentylone (Ephylone) intoxications: Quantitative confirmation and metabolite identification in authentic human biological specimens. J Anal Toxicol 42:467–475. https://doi.org/10.1093/jat/bky025
Kumblathan T, Liu Y, Uppal GK et al (2021) Wastewater-based epidemiology for community monitoring of SARS-CoV-2: Progress and challenges. ACS Environmental Au 1:18–31. https://doi.org/10.1021/acsenvironau.1c00015
Kummerer K, Steger-Hartmann T, Meyer M (1997) Biodegradability of the anti-tumour agent ifosfamide and its occurrence in hospital effluents and communal sewage. Water Res 31:2705–2710. https://doi.org/10.1016/S0043-1354(97)00121-8
Lai FY, Been F, Covaci A et al (2017) Novel wastewater-based epidemiology approach based on liquid chromatography–tandem mass spectrometry for assessing population exposure to tobacco-specific toxicants and carcinogens. Anal Chem 89:9268–9278. https://doi.org/10.1021/acs.analchem.7b02052
Lang R, Lang T, Bader M et al (2017) High-throughput quantitation of proline betaine in foods and suitability as a valid biomarker for citrus consumption. J Agr Food Chem 65:1613–1619. https://doi.org/10.1021/acs.jafc.6b05824
Li J, Gao J, Thai PK et al (2020) Transformation of illicit drugs and pharmaceuticals in sewer sediments. Environ Sci Technol 54:13056–13065. https://doi.org/10.1021/acs.est.0c04266
Li J, Gao J, Zheng Q et al (2021) Effects of pH, temperature, suspended solids, and biological activity on transformation of illicit drug and pharmaceutical biomarkers in sewers. Environ Sci Technol 55:8771–8782. https://doi.org/10.1021/acs.est.1c01516
Lin W, Huang Z, Gao S et al (2021a) Evaluating the stability of prescription drugs in municipal wastewater and sewers based on wastewater-based epidemiology. Sci Total Environ 754:142414. https://doi.org/10.1016/j.scitotenv.2020.142414
Lin X, Choi PM, Thompson J et al (2021b) Systematic evaluation of the in-sample stability of selected pharmaceuticals, illicit drugs, and their metabolites in wastewater. Environ Sci Technol 55:7418–7429. https://doi.org/10.1021/acs.est.1c00396
Ling Y, Xu S, Lin Y et al (2020) Persistence and clearance of viral rna in 2019 novel coronavirus disease rehabilitation patients. Chinese Med. J-Peking 133:1039–1043. https://doi.org/10.1097/CM9.0000000000000774
Liu Y, Li T, Deng Y et al (2021) Stability of SARS-CoV-2 on environmental surfaces and in human excreta. J Hosp Infect 107:105–107. https://doi.org/10.1016/j.jhin.2020.10.021
Liu A, Lin W, Ming R et al (2022) Stability of 28 typical prescription drugs in sewer systems and interaction with the biofilm bacterial community. J Hazard Mater 436:129142. https://doi.org/10.1016/j.jhazmat.2022.129142
Llorca M, Gros M, Rodríguez-Mozaz S et al (2014) Sample preservation for the analysis of antibiotics in water. J Chromatogr A 1369:43–51. https://doi.org/10.1016/j.chroma.2014.09.089
Lodge JK, Ridlington J, Leonard S et al (2001) Alpha- and gamma-tocotrienols are metabolized to carboxyethyl-hydroxychroman derivatives and excreted in human urine. Lipids 36:43–48. https://doi.org/10.1007/s11745-001-0666-z
López-García E, Pérez-López C, Postigo C et al (2020) Assessing alcohol consumption through wastewater-based epidemiology: Spain as a case study. Drug Alcohol Depen 215:108241. https://doi.org/10.1016/j.drugalcdep.2020.108241
Mardal M, Meyer MR (2014) Studies on the microbial biotransformation of the novel psychoactive substance methylenedioxypyrovalerone (MDPV) in wastewater by means of liquid chromatography-high resolution mass spectrometry/mass spectrometry. Sci Total Environ 493:588–595. https://doi.org/10.1016/j.scitotenv.2014.06.016
McAloon CJ, Boylan LM, Hamborg T et al (2016) The changing face of cardiovascular disease 2000–2012: An analysis of the world health organisation global health estimates data. Int J Cardiol 224:256–264. https://doi.org/10.1016/j.ijcard.2016.09.026
McCall A, Bade R, Kinyua J et al (2016) Critical review on the stability of illicit drugs in sewers and wastewater samples. Water Res 88:933–947. https://doi.org/10.1016/j.watres.2015.10.040
McCall A, Palmitessa R, Blumensaat F et al (2017) Modeling in-sewer transformations at catchment scale – Implications on drug consumption estimates in wastewater-based epidemiology. Water Res 122:655–668. https://doi.org/10.1016/j.watres.2017.05.034
Monteiro S, Rente D, Cunha MV et al (2022) A wastewater-based epidemiology tool for COVID-19 surveillance in Portugal. Sci Total Environ 804:150264. https://doi.org/10.1016/j.scitotenv.2021.150264
Murray CJ, Vos T, Lozano R et al (2012) Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: A systematic analysis for the Global Burden of Disease Study 2010. Lancet 380:2197–2223. https://doi.org/10.1016/S0140-6736(12)61689-4
Nguyen HT, Thai PK, Kaserzon SL et al (2018) Assessment of drugs and personal care products biomarkers in the influent and effluent of two wastewater treatment plants in Ho Chi Minh City, Vietnam. Sci Total Environ 631–632:469–475. https://doi.org/10.1016/j.scitotenv.2018.02.309
O'Brien JW, Thai PK, Eaglesham G et al (2014) A model to estimate the population contributing to the wastewater using samples collected on census day. Environ Sci Technol 48:517–525. https://doi.org/10.1021/es403251g
O’Brien JW, Choi PM, Li J et al (2019) Evaluating the stability of three oxidative stress biomarkers under sewer conditions and potential impact for use in wastewater-based epidemiology. Water Res 166:115068. https://doi.org/10.1016/j.watres.2019.115068
Pandopulos AJ, Bade R, Tscharke BJ et al (2021) Application of catecholamine metabolites as endogenous population biomarkers for wastewater-based epidemiology. Sci Total Environ 763:142992. https://doi.org/10.1016/j.scitotenv.2020.142992
Pawankar R (2014) Allergic diseases and asthma: A global public health concern and a call to action. World Allergy Organization J 7:12–12. https://doi.org/10.1186/1939-4551-7-12
Postigo C, de Alda ML, Barceló D (2011) Evaluation of drugs of abuse use and trends in a prison through wastewater analysis. Environ Int 37:49–55. https://doi.org/10.1016/j.envint.2010.06.012
Potischman N, Freudenheim JL (2003) Biomarkers of nutritional exposure and nutritional status. J Nutr 133:873S-874S. https://doi.org/10.1093/jn/133.3.873S
Racamonde I, Rodil R, Quintana JB et al (2014) Determination of benzodiazepines, related pharmaceuticals and metabolites in water by solid-phase extraction and liquid-chromatography–tandem mass spectrometry. J Chromatogr A 1352:69–79. https://doi.org/10.1016/j.chroma.2014.05.064
Rafael L, Mohsen N, Kyle F et al (2013) Global and regional mortality from 235 causes of death for 20 age- groups in 1990 and 2010: A systematic analysis. Lancet 381:628. https://doi.org/10.1016/S0140-6736(12)61728-0
Ramin P, Brock AL, Causanilles A et al (2017) Transformation and sorption of illicit drug biomarkers in sewer biofilms. Environ Sci Technol 51:10572–10584. https://doi.org/10.1021/acs.est.6b06277
Ramin P, Polesel F, Brock AL et al (2018) The impact of temperature on the transformation of illicit drug biomarkers in wastewater. Sci Total Environ 644:1612–1616. https://doi.org/10.1016/j.scitotenv.2018.06.307
Reid MJ, Langford KH, Mørland J et al (2011) Analysis and interpretation of specific ethanol metabolites, ethyl sulfate, and ethyl glucuronide in sewage effluent for the quantitative measurement of regional alcohol consumption. Alcohol Clin Exp Res 9:1593–1599. https://doi.org/10.1111/j.1530-0277.2011.01505.x
Richard B, Maulik G, White J et al (2020) Determination of prescribed and designer benzodiazepines and metabolites in influent wastewater. Anal Methods-UK 12:3637–3644. https://doi.org/10.1039/d0ay00560f
Rico M, Andrés-Costa MJ, Picó Y (2017) Estimating population size in wastewater-based epidemiology. Valencia metropolitan area as a case study. J Hazard Mater 323:156–165. https://doi.org/10.1016/j.jhazmat.2016.05.079
Rodríguez-Álvarez T, Rodil R, Rico M et al (2014) Assessment of local tobacco consumption by liquid chromatography–tandem mass spectrometry sewage analysis of nicotine and its metabolites, cotinine and trans-3′-hydroxycotinine, after enzymatic deconjugation. Anal Chem 86:10274–10281. https://doi.org/10.1021/ac503330c
Ryu Y, Reid MJ, Thomas KV (2015) Liquid chromatography–high resolution mass spectrometry with immunoaffinity clean-up for the determination of the oxidative stress biomarker 8-iso-prostaglandin f2alpha in wastewater. J Chromatogr A 1409:146–151. https://doi.org/10.1016/j.chroma.2015.07.060
Schultz MM, Furlong ET (2008) Trace analysis of antidepressant pharmaceuticals and their select degradates in aquatic matrixes by LC/ESI/MS/MS. Anal Chem 80:1756–1762. https://doi.org/10.1021/ac702154e
Senta I, Krizman I, Ahel M et al (2014) Assessment of stability of drug biomarkers in municipal wastewater as a factor influencing the estimation of drug consumption using sewage epidemiology. Sci Total Environ 487:659–665. https://doi.org/10.1016/j.scitotenv.2013.12.054
Shu C, Gong D, Chang J et al (2021) Research progresses on abusing flunitrazepam and detection. Forensic Sci Technol 46:182–186. https://doi.org/10.16467/j.1008-3650.2021.0045 (in Chinese)
Smith HS (2009) Opioid metabolism. Mayo Clin Proc 84:572–575. https://doi.org/10.4065/84.7.613
Thai PK, Jiang G, Gernjak W et al (2014) Effects of sewer conditions on the degradation of selected illicit drug residues in wastewater. Water Res 48:538–547. https://doi.org/10.1016/j.watres.2013.10.019
Thai PK, Lai FY, Bruno R et al (2016) Refining the excretion factors of methadone and codeine for wastewater analysis — Combining data from pharmacokinetic and wastewater studies. Environ Int 94:307–314. https://doi.org/10.1016/j.envint.2016.05.033
Thai PK, O’Brien JW, Banks APW et al (2019) Evaluating the in-sewer stability of three potential population biomarkers for application in wastewater-based epidemiology. Sci Total Environ 671:248–253. https://doi.org/10.1016/j.scitotenv.2019.03.231
Thai PK, Tscharke BJ, O Brien JW et al (2021) Estimating alcohol consumption by wastewater-based epidemiology: An assessment of the correction factor for ethyl sulfate using large-scale national monitoring data. Environ Sci Technol Lett 8:333–338. https://doi.org/10.1021/acs.estlett.1c00065
Thomaidis NS, Gago-Ferrero P, Ort C et al (2016) Reflection of socioeconomic changes in wastewater: licit and illicit drug use patterns. Environ Sci Technol 50:10065–10072. https://doi.org/10.1021/acs.est.6b02417
Thongprachum A, Fujimoto T, Takanashi S et al (2018) Detection of nineteen enteric viruses in raw sewage in Japan. Infect Genet Evol 63:17–23. https://doi.org/10.1016/j.meegid.2018.05.006
Tisha J, Walsh G, Tokmakejian S et al (2008) Increase of urinary 5-hydroxyindoleacetic acid excretion but not serum chromogranin a following over-the-counter 5-hydroxytryptophan intake. Can J Gastroenterol 22:49–53. https://doi.org/10.1155/2008/472159
Tscharke BJ, White JM, Gerber JP (2016) Estimates of tobacco use by wastewater analysis of anabasine and anatabine. Drug Test Anal 8:702–707. https://doi.org/10.1002/dta.1842
Tsuji T, Fukuwatari T, Sasaki S et al (2010) Urinary excretion of vitamin B1, B2, B6, niacin, pantothenic acid, folate, and vitamin c correlates with dietary intakes of free-living elderly, female Japanese. Nutr Res 30:171–178. https://doi.org/10.1016/j.nutres.2010.02.001
Tsuji T, Fukuwatari T, Sasaki S et al (2011) Twenty-four-hour urinary water-soluble vitamin levels correlate with their intakes in free-living Japanese schoolchildren. Public Health Nutr 14:327–333. https://doi.org/10.1017/S1368980010001904
UNODC (2013) World drug report
UNODC (2015) World drug report
van Nuijs ALN, Castiglioni S, Tarcomnicu I et al (2011a) Illicit drug consumption estimations derived from wastewater analysis: A critical review. Sci Total Environ 409:3564–3577. https://doi.org/10.1016/j.scitotenv.2010.05.030
van Nuijs ALN, Mougel J, Tarcomnicu I et al (2011b) Sewage epidemiology — A real-time approach to estimate the consumption of illicit drugs in brussels. Belgium Environ Int 37:612–621. https://doi.org/10.1016/j.envint.2010.12.006
van Nuijs ALN, Abdellati K, Bervoets L et al (2012) The stability of illicit drugs and metabolites in wastewater, an important issue for sewage epidemiology? J Hazard Mater 239–240:19–23. https://doi.org/10.1016/j.jhazmat.2012.04.030
van Nuijs ALN, Covaci A, Beyers H et al (2015) Do concentrations of pharmaceuticals in sewage reflect prescription figures? Environ Sci Pollut R 22:9110–9118. https://doi.org/10.1007/s11356-014-4066-2
Victoria B, Crispin H, Neville L et al (2014) Prioritising anticancer drugs for environmental monitoring and risk assessment purposes. Sci Total Environ 473:159–170. https://doi.org/10.1016/j.watres.2015.10.024
Viollet B, Guigas B, Garcia NS et al (2012) Cellular and molecular mechanisms of metformin: An overview. Clin Sci 122:253–270. https://doi.org/10.1042/CS20110386
Xiao F, Tang M, Zheng X et al (2020) Evidence for gastrointestinal infection of SARS-cov-2. Gastroenterology 158:1831-1833.e3. https://doi.org/10.1053/j.gastro.2020.02.055
Xu Z, Du P, Li K et al (2017) Tracing methamphetamine and amphetamine sources in wastewater and receiving waters via concentration and enantiomeric profiling. Sci Total Environ 601–602:159–166. https://doi.org/10.1016/j.scitotenv.2017.05.045
Xu Y, Li X, Zhu B et al (2020) Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding. Nat Med 26:502–505. https://doi.org/10.1038/s41591-020-0817-4
Yan J, Xiao Y, Tan D et al (2019) Wastewater analysis reveals spatial pattern in consumption of anti-diabetes drug metformin in China. Chemosphere 222:688–695. https://doi.org/10.1016/j.chemosphere.2019.01.151
Yao B, Yan S, Lian L et al (2018) Occurrence and indicators of pharmaceuticals in Chinese streams: A nationwide study. Environ Pollut 236:889–898. https://doi.org/10.1016/j.envpol.2017.10.032
Yu X, Sui Q, Lyu S et al (2020) Municipal solid waste landfills: An underestimated source of pharmaceutical and personal care products in the water environment. Environ Sci Technol 54:9757–9768. https://doi.org/10.1021/acs.est.0c00565
Zhang S, Zhang Q, Liu Y et al (2020) Emission and fate of antibiotics in the Dongjiang River basin, China: Implication for antibiotic resistance risk. Sci Total Environ 712:136518. https://doi.org/10.1016/j.scitotenv.2020.136518
Zheng Q, Eaglesham G, Tscharke BJ et al (2020) Determination of anabasine, anatabine, and nicotine biomarkers in wastewater by enhanced direct injection LC-MS/MS and evaluation of their in-sewer stability. Sci Total Environ 743:140551. https://doi.org/10.1016/j.scitotenv.2020.140551
Zheng Q, Ren Y, Wang Z et al (2021) Assessing patterns of illicit drug use in a Chinese city by analyzing daily wastewater samples over a one-year period. J Hazard Mater 417:125999. https://doi.org/10.1016/j.jhazmat.2021.125999
Zuccato E, Chiabrando C, Castiglioni S et al (2005) Cocaine in surface waters: a new evidence-based tool to monitor community drug abuse. Environ Health-Glob 4:14–14. https://doi.org/10.1186/1476-069X-4-14
Zuccato E, Chiabrando C, Castiglioni S et al (2008) Estimating community drug abuse by wastewater analysis. Environ Health Persp 116:1027–1032. https://doi.org/10.1289/ehp.11022
Funding
This work was supported by the National Natural Science Foundation of China (Grant No. 4187746), the Natural Science Foundation of Guangdong Province (Grant No. 2019A1515011037), and the Key Laboratory of Monitoring and Safety of Psychoactive Substances of Guangdong Province.
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Zhihan Gao: investigation, data curation, writing-original draft, methodology.
Ping Li: investigation, writing-review & editing.
Han Lin: investigation, data curation.
Wenting Lin: investigation, writing-review & editing.
Yuan Ren, Yuan Ren: writing-review & editing, supervision, project administration, funding acquisition.
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Gao, Z., Li, P., Lin, H. et al. Biomarker selection strategies based on compound stability in wastewater-based epidemiology. Environ Sci Pollut Res 30, 5516–5529 (2023). https://doi.org/10.1007/s11356-022-24268-y
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DOI: https://doi.org/10.1007/s11356-022-24268-y