Feature pubs.acs.org/est
Working Upstream: How Far Can You Go with Sewage-Based Drug Epidemiology? Daniel A. Burgard,*,† Caleb Banta-Green,‡ and Jennifer A. Field§ †
Chemistry Department, University of Puget Sound, Tacoma Washington 98416, United States Alcohol and Drug Abuse Institute, University of Washington, Seattle Washington 98105, United States § Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis Oregon 97331, United States analytes by 2−4 orders of magnitude. With these techniques, quantification of drugs at even the subpart per trillion range (ppt) is possible. Jones-Lepp et al. reported the first detection of two drugs, methamphetamine (a pharmaceutical and illicitly manufactured drug) and methylenedioxymethamphetamine (MDMA, commonly referred to as ecstasy, an illicit drug) in the effluent of two wastewater treatment plants (WWTPs) in the U.S.2 Interestingly, the idea of a community-scale surveillance tool using sewage was actually proposed three years earlier by Christian Daughton at the U.S. Environmental Protection Agency.3 The field received worldwide media attention when a group from the Mario Negri Institute for Pharmacological The field of drug epidemiology based upon sewer sampling has Research in Milan quantified the metabolite of cocaine, only emerged in the last 10 years and has great potential to aid benzoylecgonine (BE), in Italy at four WWTPs and the Po in drug epidemiological studies. This rapidly expanding field River. This study which was led by Ettore Zuccato extended the can provide an unbiased look into the illicit drug habits of large scope of the previous work and pioneered using concentration populations as well as specific, smaller groups. How far the field data to roughly back-calculate population use in this Italian has evolved is discussed as well as where the future for these region.4 This study found 25 ng/L of BE in the river water and types of monitoring studies could go. as high as 750 ng/L at a WWTP. With these data, it was estimated that four kilograms of cocaine residues traveled daily INTRODUCTION in the river, which is equivalent to about 40 000 daily doses Analysis of sewage is nothing new. A movement for “securing from the river basin’s 1.4 million young adults. National the adoption of more uniform and efficient methods of water estimates were closer to 15 000 doses/month for this age analysis” led to a 1889 report published by the Chemical group. The gap in these estimates has raised questions and has Section of the American Association for the Advancement of led to efforts to improve and standardize sampling, chemical 1 Science (AAAS). This report covered five topics: ammonia, analysis and statistical approaches. In less than 10 years, the oxygen-consuming capacity, total nitrogen as nitrates and field has rapidly expanded from the initial studies in the U.S. at nitrites, nitrogen as nitrites, and a statement of results. In a single location and in Italy with a single drug, to include recognition of creating standard methods for analysis, the first current projects such as a coordinated study among 19 edition of Standard Methods of Water Analysis was published European cities to measure a cocktail of compounds including in 1905 and by its seventh edition in 1933 the title had changed the biomarkers of cocaine, amphetamine, methamphetamine, to Standard Methods of the Examination of Water and ecstasy and cannabis.5 These types of studies are part of the 1 Sewage. Many methods and analytes have changed in 100 emerging, cross-disciplinary field of sewer-based drug epidemiyears but the environmental concerns surrounding sewage and ology as illustrated in Figure 1. This area of research has mostly its impact on public health are still present today. New taken off in Europe and Australia with a handful of studies technologies are allowing for the detection and quantification of occurring in North America. trace amounts of bioactive compounds in surface and wastewaters. Detection of illicit drugs became possible at the CURRENT DRUG ESTIMATES ppb-ppt level due to advances in mass spectrometry (MS) Many limitations exist for the conventional ways of determining coupled to liquid chromatography (LC). This instrumentation drug use at the population level. Data for estimating the illicit exploits the fact that each drug has a relatively unique MS/MS drug use of a population typically come from surveys, drug fingerprint when correlated to retention time. LC-MS/MS abuse treatment centers, drug abuse related hospital visits, fatal identification is aided by preconcentration steps used to pull overdoes, telephone hotlines, and law enforcement numbers out trace amounts of drugs from dilute solutions. Techniques from arrests, seizures, and trafficking.6 Each of these metrics has such as solid phase extraction use chemical attractions such as their own weakness for representing a population as shown in lipophilic and/or ion exchange interactions to extract analytes from up to a liter of solution or more onto resins that can then be eluted in small volumes of solvent, effectively concentrating Published: December 17, 2013 ‡
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© 2013 American Chemical Society
1362
dx.doi.org/10.1021/es4044648 | Environ. Sci. Technol. 2014, 48, 1362−1368
Environmental Science & Technology
Feature
found BE in 22 of 24 samples at a mean concentration of 45 ng/L and a maximum of 130 ng/L.16 If our goal is to monitor and clean up the environment, then we need to focus on source abatement and the most likely sources for the release of these drugs are upstream at WWTPs. WWTP effluent had been studied extensively in order to determine which compounds and how much are getting into the environment. The next natural question is how effective is a WWTP at removing these compounds which requires measurement of both the plant’s effluent and ‘upstream’ at the plant’s influent. It is at the point of sampling WWTP influent that the waters get murky (figuratively and literally) as far as where environmental monitoring stops and the drug epidemiology starts. Numerous studies have utilized samples of influent at WWTPs and reported estimates of drug consumption for the cities they serve. Treatment plants serving populations from hundreds to hundreds of thousands of people have been studied. Figure 2 shows areas around the world where sewagebased drug epidemiological studies have been performed. Figure 3 shows the steps and considerations required for sewerbased drug epidemiology. Some studies collect samples (most often composite samples from 24 h time periods) for only a week or two to estimate drug consumption while others make extensive measurements over a year or more to try to determine trends in drug use. The generally expected higher use of cocaine and ecstasy, and amphetamine on weekends have been shown in sewage analysis whereas use of heroin was more consistent throughout the week.20 A European sewage study reported drug consumption estimates that were similar to survey data during the same period with reported increased use rates of marijuana and amphetamines and declining rates of cocaine and heroin.21 A study from Oslo, Norway compared three complementary techniques for estimating cocaine consumption: survey questionnaires, oral-fluid samples from drivers, and sewage analysis.22 This critical comparison concluded that the three techniques provide a well-balanced assessment of community drug use but all three techniques suffer from shortfalls. One study interested in drug use trends around a specific event monitored a city’s waste stream during the National Football League’s Super Bowl, but found little difference between drug use on that day and a baseline weekend.23 A project at the regional level covered WWTPs at 96 municipalities encompassing 65% of the state of Oregon and compared the urban and rural uses of cocaine, MDMA, and methamphetamine.24 WWTP loading of cocaine and MDMA were found to be higher in urban areas and no significant
Figure 1. The mixing of three fields leads to sewer-based drug epidemiology.
Table 1. Surveys using self-report data are the most common but suffer from sampling and response biases as well as from being costly. Additionally, survey data suffer from time lags that can affect the relevance and utility of data.7 However, the U.S. government determines how to spend billions of dollars to combat drugs each year using these imperfect data sources.8
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ENVIRONMENTAL SCIENTIST MEET DRUG EPIDEMIOLOGIST In the past few years the rapid advance of the analytical technology and a burgeoning number of applications of sewagebased drug epidemiology have led to multiple reviews and critical reviews across a broad spectrum of analytical, environmental, and toxicological literature.9−15 But why do we, as environmental researchers (and readers of ES&T), care about population level drug abuse? First, our knowledge and skill set is of value to those working in other areas of public health and medicine. Second, we are interested in the identification, quantification, and persistence of compounds released to the environment. Thus, with the skill set to measure these compounds, we set out to do so. Studies have reported drugs of abuse and their metabolites in surface waters, groundwater, and even in treated drinking water.16−19 For example, in a study monitoring 21 drugs of abuse in urban groundwater, MDMA, cocaine, and benzoyleconine (BE, cocaine’s metabolite), were found in groundwater at levels up to 30 ng/L, 60 ng/L, and 20 ng/L, respectively.19 A study that reported on the presence of five drugs of abuse and one metabolite in Spanish tap waters
Table 1. Major Sources of Epidemiological Illicit Drug Use Data7 data type
population description
drug abuse warning network national telephone surveys school surveys treatment center admissions fatal overdoses
hospital E.R. patients ≥18
community-based surveys sewage-based
population size
frequency
report time lag
strengths
weaknesses
hundreds-thousands
annual
1 year
annual
1−2 Years
Working Upstream: How Far Can You Go with Sewage-Based Drug Epidemiology? Daniel A. Burgard,*,† Caleb Banta-Green,‡ and Jennifer A. Field§ †
Chemistry Department, University of Puget Sound, Tacoma Washington 98416, United States Alcohol and Drug Abuse Institute, University of Washington, Seattle Washington 98105, United States § Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis Oregon 97331, United States analytes by 2−4 orders of magnitude. With these techniques, quantification of drugs at even the subpart per trillion range (ppt) is possible. Jones-Lepp et al. reported the first detection of two drugs, methamphetamine (a pharmaceutical and illicitly manufactured drug) and methylenedioxymethamphetamine (MDMA, commonly referred to as ecstasy, an illicit drug) in the effluent of two wastewater treatment plants (WWTPs) in the U.S.2 Interestingly, the idea of a community-scale surveillance tool using sewage was actually proposed three years earlier by Christian Daughton at the U.S. Environmental Protection Agency.3 The field received worldwide media attention when a group from the Mario Negri Institute for Pharmacological The field of drug epidemiology based upon sewer sampling has Research in Milan quantified the metabolite of cocaine, only emerged in the last 10 years and has great potential to aid benzoylecgonine (BE), in Italy at four WWTPs and the Po in drug epidemiological studies. This rapidly expanding field River. This study which was led by Ettore Zuccato extended the can provide an unbiased look into the illicit drug habits of large scope of the previous work and pioneered using concentration populations as well as specific, smaller groups. How far the field data to roughly back-calculate population use in this Italian has evolved is discussed as well as where the future for these region.4 This study found 25 ng/L of BE in the river water and types of monitoring studies could go. as high as 750 ng/L at a WWTP. With these data, it was estimated that four kilograms of cocaine residues traveled daily INTRODUCTION in the river, which is equivalent to about 40 000 daily doses Analysis of sewage is nothing new. A movement for “securing from the river basin’s 1.4 million young adults. National the adoption of more uniform and efficient methods of water estimates were closer to 15 000 doses/month for this age analysis” led to a 1889 report published by the Chemical group. The gap in these estimates has raised questions and has Section of the American Association for the Advancement of led to efforts to improve and standardize sampling, chemical 1 Science (AAAS). This report covered five topics: ammonia, analysis and statistical approaches. In less than 10 years, the oxygen-consuming capacity, total nitrogen as nitrates and field has rapidly expanded from the initial studies in the U.S. at nitrites, nitrogen as nitrites, and a statement of results. In a single location and in Italy with a single drug, to include recognition of creating standard methods for analysis, the first current projects such as a coordinated study among 19 edition of Standard Methods of Water Analysis was published European cities to measure a cocktail of compounds including in 1905 and by its seventh edition in 1933 the title had changed the biomarkers of cocaine, amphetamine, methamphetamine, to Standard Methods of the Examination of Water and ecstasy and cannabis.5 These types of studies are part of the 1 Sewage. Many methods and analytes have changed in 100 emerging, cross-disciplinary field of sewer-based drug epidemiyears but the environmental concerns surrounding sewage and ology as illustrated in Figure 1. This area of research has mostly its impact on public health are still present today. New taken off in Europe and Australia with a handful of studies technologies are allowing for the detection and quantification of occurring in North America. trace amounts of bioactive compounds in surface and wastewaters. Detection of illicit drugs became possible at the CURRENT DRUG ESTIMATES ppb-ppt level due to advances in mass spectrometry (MS) Many limitations exist for the conventional ways of determining coupled to liquid chromatography (LC). This instrumentation drug use at the population level. Data for estimating the illicit exploits the fact that each drug has a relatively unique MS/MS drug use of a population typically come from surveys, drug fingerprint when correlated to retention time. LC-MS/MS abuse treatment centers, drug abuse related hospital visits, fatal identification is aided by preconcentration steps used to pull overdoes, telephone hotlines, and law enforcement numbers out trace amounts of drugs from dilute solutions. Techniques from arrests, seizures, and trafficking.6 Each of these metrics has such as solid phase extraction use chemical attractions such as their own weakness for representing a population as shown in lipophilic and/or ion exchange interactions to extract analytes from up to a liter of solution or more onto resins that can then be eluted in small volumes of solvent, effectively concentrating Published: December 17, 2013 ‡
■
■
© 2013 American Chemical Society
1362
dx.doi.org/10.1021/es4044648 | Environ. Sci. Technol. 2014, 48, 1362−1368
Environmental Science & Technology
Feature
found BE in 22 of 24 samples at a mean concentration of 45 ng/L and a maximum of 130 ng/L.16 If our goal is to monitor and clean up the environment, then we need to focus on source abatement and the most likely sources for the release of these drugs are upstream at WWTPs. WWTP effluent had been studied extensively in order to determine which compounds and how much are getting into the environment. The next natural question is how effective is a WWTP at removing these compounds which requires measurement of both the plant’s effluent and ‘upstream’ at the plant’s influent. It is at the point of sampling WWTP influent that the waters get murky (figuratively and literally) as far as where environmental monitoring stops and the drug epidemiology starts. Numerous studies have utilized samples of influent at WWTPs and reported estimates of drug consumption for the cities they serve. Treatment plants serving populations from hundreds to hundreds of thousands of people have been studied. Figure 2 shows areas around the world where sewagebased drug epidemiological studies have been performed. Figure 3 shows the steps and considerations required for sewerbased drug epidemiology. Some studies collect samples (most often composite samples from 24 h time periods) for only a week or two to estimate drug consumption while others make extensive measurements over a year or more to try to determine trends in drug use. The generally expected higher use of cocaine and ecstasy, and amphetamine on weekends have been shown in sewage analysis whereas use of heroin was more consistent throughout the week.20 A European sewage study reported drug consumption estimates that were similar to survey data during the same period with reported increased use rates of marijuana and amphetamines and declining rates of cocaine and heroin.21 A study from Oslo, Norway compared three complementary techniques for estimating cocaine consumption: survey questionnaires, oral-fluid samples from drivers, and sewage analysis.22 This critical comparison concluded that the three techniques provide a well-balanced assessment of community drug use but all three techniques suffer from shortfalls. One study interested in drug use trends around a specific event monitored a city’s waste stream during the National Football League’s Super Bowl, but found little difference between drug use on that day and a baseline weekend.23 A project at the regional level covered WWTPs at 96 municipalities encompassing 65% of the state of Oregon and compared the urban and rural uses of cocaine, MDMA, and methamphetamine.24 WWTP loading of cocaine and MDMA were found to be higher in urban areas and no significant
Figure 1. The mixing of three fields leads to sewer-based drug epidemiology.
Table 1. Surveys using self-report data are the most common but suffer from sampling and response biases as well as from being costly. Additionally, survey data suffer from time lags that can affect the relevance and utility of data.7 However, the U.S. government determines how to spend billions of dollars to combat drugs each year using these imperfect data sources.8
■
ENVIRONMENTAL SCIENTIST MEET DRUG EPIDEMIOLOGIST In the past few years the rapid advance of the analytical technology and a burgeoning number of applications of sewagebased drug epidemiology have led to multiple reviews and critical reviews across a broad spectrum of analytical, environmental, and toxicological literature.9−15 But why do we, as environmental researchers (and readers of ES&T), care about population level drug abuse? First, our knowledge and skill set is of value to those working in other areas of public health and medicine. Second, we are interested in the identification, quantification, and persistence of compounds released to the environment. Thus, with the skill set to measure these compounds, we set out to do so. Studies have reported drugs of abuse and their metabolites in surface waters, groundwater, and even in treated drinking water.16−19 For example, in a study monitoring 21 drugs of abuse in urban groundwater, MDMA, cocaine, and benzoyleconine (BE, cocaine’s metabolite), were found in groundwater at levels up to 30 ng/L, 60 ng/L, and 20 ng/L, respectively.19 A study that reported on the presence of five drugs of abuse and one metabolite in Spanish tap waters
Table 1. Major Sources of Epidemiological Illicit Drug Use Data7 data type
population description
drug abuse warning network national telephone surveys school surveys treatment center admissions fatal overdoses
hospital E.R. patients ≥18
community-based surveys sewage-based
population size
frequency
report time lag
strengths
weaknesses
hundreds-thousands
annual
1 year
annual
1−2 Years
