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Wastewater-Based Epidemiology as a Novel Biomonitoring Tool to Evaluate Human Exposure To Pollutants Emma Gracia-Lor,†,‡,§ Nikolaos I. Rousis,†,§ Feĺ ix Hernań dez,‡ Ettore Zuccato,† and Sara Castiglioni*,† †
Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Department of Environmental Health Sciences, Milan, Italy Research Institute for Pesticides and Water, Universitat Jaume I, Castellón, Spain alcohol use, and appropriate biomarkers have been proposed to this aim.3,4 Urban wastewater analysis can be best described as a largescale urine test, as the collective wastewater from a city pools anonymous urine samples of thousands of individuals. Thus, WBE is a promising tool that can provide the human exposure profile to a substance at the population level. This can be done by analyzing only a few samples collected at the inlet of an urban wastewater treatment plant (usually as 24 h composite samples). Therefore, results can be obtained in a shorter period of time, and at less cost than with HBM studies. This manuscript suggests a panel of new potential WBE biomarkers for monitoring human exposure to some of the most widespread pollutants (Table 1). The biomarkers were selected among those commonly investigated in HBM studies, including several classes for which very few or even no information is available (i.e., mycotoxins, nitrosamines, and carbamates) and some emerging pollutants (i.e., acrylamide, neonicotinoids, and parabens). A WBE approach was recently developed to estimate human exposure to pesticides by measuring urinary metabolites in urban wastewater from several European cities.5 Spatial and umans are continuously exposed to pollutants by temporal variations in human intake were assessed and different routes, and human biomonitoring (HBM) is potential health risks related to human exposure were the tool commonly used to assess exposure to chemicals by evaluated by comparison with the acceptable daily intakes measuring parent substances or metabolites in human (ADI).5 Results were very promising for developing novel specimens. These data are vital for health impact assessment applications for other pollutants (Table 1). For instance, and to support environmental and health policy-making in evaluating human exposure to mycotoxins is a matter of public public health programs. However, HBM studies have some concern due to their potential adverse effects on human health, limitations, such as sampling biases, long realization time, but information on human exposure is still limited since mycotoxins are not often included in HBM studies. WBE is complexity of data elaboration to extrapolate results to the therefore an attractive complementary tool to assess exposure whole population, high costs and ethical issues. This because to mycotoxins, and our group is currently working to identify HBM includes a large number of individuals to overtake the suitable WBE biomarkers. wide variability of individual excretion profiles and extrapolate WBE is based on the selection of suitable biomarkers to data to the entire population. back-calculate population exposure. Specific requirements have Wastewater-based epidemiology (WBE) is a recent complebeen identified for a biomarker and should be carefully verified mentary approach to HBM that overcomes some of the in any new study.4 Biomarkers should be measurable in raw existing limitations. WBE is based on the chemical analysis of wastewater; released into sewers only as a result of human human metabolic excretion products (biomarkers) in urban excretion; have a well-defined excretion profile to avoid wastewater to measure the collective consumption or exposure interferences from additional exogenous or endogenous to chemicals. Monitoring wastewater has the potential to sources; not be adsorbed to suspended matter; be stable in extract useful epidemiological information from qualitative and wastewater during in-sewer transit, sampling and storage.4 For quantitative profiling of biomarkers entering the sewage instance, for pesticides it was essential to investigate the system.1 WBE is currently applied on large scale to estimate 2 existence of additional environmental sources in wastewater, drug consumption in the population, and is considered a new also looking into metabolic processes in plants, animals and indicator of drug use complementing other epidemiological indicators (http://www.emcdda.europa.eu/activities/ wastewater-analysis). Additional applications have been Received: June 20, 2018 implemented to assess pharmaceuticals, tobacco, caffeine and
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© XXXX American Chemical Society
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DOI: 10.1021/acs.est.8b01403 Environ. Sci. Technol. XXXX, XXX, XXX−XXX
phthalate substitute polycyclic aromatic hydrocarbons (PAHs) polychlorinated biphenyls (PCBs) volatile organic compounds (VOCs)
other pesticides (including neonicotinoids) phenols (including parabens) phthalates
triazines carbamates
nitrosamines pesticides pyrethroids organophosphates
acrylamide mycotoxins
class of pollutant
potential biomarkers
N-acetyl-S-(3-hydroxypropyl)-L-cysteine; N-acetyl-S-(2-carbamoylethyl)-L-cysteine; N-acetyl-S-(2-cyanoethyl)-L-cysteine; muconic acid; 2-thioxothiazolidine-4-carboxylic acid; mandelic acid; 2aminothiazoline-4-carboxylic acid; phenylglyoxylic acid
monomethyl phthalate; monoethyl phthalate; mono (n- and iso-) butyl phthalate; monobenzyl phthalate; mono-(2-ethyl-5-hydroxyhexyl); mono-n-octyl phthalate; mono-3-methyl-5-dimethylhexyl phthalate; monoethyl phthalate; mono-(2-ethyl-5-oxohexyl) phthalate; mono-(2-ethyl-5-carboxypentyl) phthalate 1,2-cyclohexane dicarboxylic acid diisononyl ester 1-hydroxyphenanthrene; 2-hydroxyphenanthrene;3-hydroxyphenanthrene; 4-hydroxyphenanthrene;9-hydroxyphenanthrene; 2-hydroxyfluorene; 3-hydroxyfluorene;9- hydroxyfluorene; 1hydroxynaphthalene; 2-hydroxynaphthalene; 1-hydroxypyrene hydroxyl-PCBs; sulfate-PCBs
3-phenoxybenzoic acid; cis-/trans-2,2-dichlorovinyl-2,2-dimethylcyclopropane-1-carboxylic acid; cis-2,2-dibromovinyl-2,2-dimethylcyclopropane-1-carboxylic acid; 4-fluoro-3-phenoxybenzoic acid diethyl phosphate; diethyl thiophosphate; dimethyl phosphate; dimethyl thiophosphate; 3,5,6-trichloro-2-pyridinol; malathion monocarboxylic acid; malathion dicarboxylic acid; 2-isopropyl-6methyl-4-pyrimidinol; 4-nitrophenol terbutylazine desethyl; atrazine desisopropyl; atrazine desethyl; atrazine desethyl desisopropyl; atrazine mercapturate 1-naphthol; 2-naphthol; methyl-5-hydroxy-2-benzimidazole carbamate; 3-hydroxy-carbofuran; aldicarb sulfoxide; aldicarb Sulphone; 2-dimethylamino-5,6-dimethyl-4-hydroxy pyrimidine; 2methylamino-5,6-dimethyl-4-hydroxy pyrimidine; 2-amino-5,6-dimethyl-4-hydroxypyrimidine; carbofuranphenol; 2-isopropoxyphenol 6-chloronicotinic acid; metolachlor mercapturate; 1-(2,4-dichlorophenyl)-2-(1H-imidazole-1-yl)-1-ethanol; 3,4-dichloroaniline; 2-chloro-1,3-thiazole-5-carboxylic acid; aminomethylphosphonic acid; 5-hydroxy-imidacloprid, 4,5-dihydroxy-imidacloprid and 4,5-dehydro-imidacloprid bisphenol A; triclosan; benzophenone-3; methyl paraben; ethyl paraben; N-propyl paraben; butyl (n- and iso-) paraben; benzyl paraben; 2,5-dichlorophenol
glycidamide deoxynivalenol; deepoxy-deoxynivalenol; nivalenol; zearalenone;β-/γ-zearalenol; fumonisin B1; fumonisin B2; fumonisin B3;aflatoxin B1; aflatoxin M1; aflatoxin B2; aflatoxin G1; aflatoxin G2; ochratoxin; citrinin; dihydrocitrinone 4-(methylnitrosamino)-1-(3pyridil)-1-butanonol
Table 1. Main Potential WBE Biomarkers Proposed for Future Studies
Environmental Science & Technology Viewpoint
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DOI: 10.1021/acs.est.8b01403 Environ. Sci. Technol. XXXX, XXX, XXX−XXX
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Environmental Science & Technology foodstuff and their presence in the domestic environment.5 Searching suitable WBE biomarkers for polycyclic aromatic hydrocarbons (PAHs) might require a similar approach because they are ubiquitous pollutants with various solubility and lipophilicity characteristics and multiple routes of transformation. PAHs are formed by the incomplete combustion of organic materials, and are released into air ending up both in soils and waters. Since the main potential biomarkers are hydroxyl metabolites (Table 1), a thorough investigation of all potential sources should be done in order to exclude other sources than human metabolism. Also phthalates are ubiquitous pollutants, generally lipophilic, but they are subjected to rapid environmental transformation and human metabolism. The most common metabolic products are monoesters which are further metabolized by oxidation and/ or glucuronidation, thus increasing their water solubility. Phthalates metabolites are therefore very likely to be found in wastewater as WBE biomarkers, but environmental sources should be carefully evaluated. The most critical requirement to be verified for lipophilic chemicals, such as polychlorinated biphenyls (PCBs), is the sorption onto sewage suspended matter. In fact, metabolic products (Table 1) may retain the lipophilic characteristics and are likely to adsorb to particulate matter. Although PCBs were banned from commercial production, they are still contained in a wide range of products used daily resulting into release in the environment and human exposure through food and air. Finally, the main requirement of volatile organic compounds (VOCs) which has to be verified is the stability in sewers of their metabolic products, since they are likely to pass in the air during the transport of wastewater. This might require field studies to assess biomarkers stability in-sewer, which are now limited to laboratory experiments and modeling studies. WBE can count on a very robust and standardized methodology able to produce reliable and comparable results, thus we believe it can serve as a powerful complementary HBM tool to provide valuable information for public health in the near future. We suggested several fields of application for obtaining reliable and up-to-date information on population exposure to a wide range of pollutants. Data generated by WBE will be of interest for policy-making and international agencies related to public health issues. It would be particularly useful to establish close collaboration with public health agencies in order to integrate WBE into the current HBM framework for checking community level exposure to pollutants, and boosting information on community health status.
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Emma Gracia-Lor extends her gratitude to Generalitat Valenciana, Conselleria d’Educaciô, Investigació, Cultura i Esport for her postdoctoral contract (APOSTD/2015, Programa VALi+d). Notes
The authors declare no competing financial interest.
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REFERENCES
(1) Zuccato, E.; Chiabrando, C.; Castiglioni, S.; Bagnati, R.; Fanelli, R. Estimating community drug abuse by wastewater analysis. Environ. Health Perspect 2008, 116 (8), 1027−32. (2) Ort, C.; van Nuijs, A. L.; Berset, J. D.; Bijlsma, L.; Castiglioni, S.; Covaci, A.; de Voogt, P.; Emke, E.; Fatta-Kassinos, D.; Griffiths, P.; Hernandez, F.; Gonzalez-Marino, I.; Grabic, R.; Kasprzyk-Hordern, B.; Mastroianni, N.; Meierjohann, A.; Nefau, T.; Ostman, M.; Pico, Y.; Racamonde, I.; Reid, M.; Slobodnik, J.; Terzic, S.; Thomaidis, N.; Thomas, K. V. Spatial differences and temporal changes in illicit drug use in Europe quantified by wastewater analysis. Addiction 2014, 109 (8), 1338−52. (3) Thomas, K. V.; Reid, M. J. What else can the analysis of sewage for urinary biomarkers reveal about communities? Environ. Sci. Technol. 2011, 45 (18), 7611−2. (4) Gracia-Lor, E.; Castiglioni, S.; Bade, R.; Been, F.; Castrignano, E.; Covaci, A.; Gonzalez-Marino, I.; Hapeshi, E.; Kasprzyk-Hordern, B.; Kinyua, J.; Lai, F. Y.; Letzel, T.; Lopardo, L.; Meyer, M. R.; O’Brien, J.; Ramin, P.; Rousis, N. I.; Rydevik, A.; Ryu, Y.; Santos, M. M.; Senta, I.; Thomaidis, N. S.; Veloutsou, S.; Yang, Z.; Zuccato, E.; Bijlsma, L. Measuring biomarkers in wastewater as a new source of epidemiological information: Current state and future perspectives. Environ. Int. 2017, 99, 131−150. (5) Rousis, N. I.; Gracia-Lor, E.; Zuccato, E.; Bade, R.; Baz-Lomba, J. A.; Castrignano, E.; Causanilles, A.; Covaci, A.; de Voogt, P.; Hernandez, F.; Kasprzyk-Hordern, B.; Kinyua, J.; McCall, A. K.; Plosz, B. G.; Ramin, P.; Ryu, Y.; Thomas, K. V.; van Nuijs, A.; Yang, Z.; Castiglioni, S. Wastewater-based epidemiology to assess panEuropean pesticide exposure. Water Res. 2017, 121, 270−279.
AUTHOR INFORMATION
Corresponding Author
*Phone: +39 02 39014776; fax: +39 02 39014735; e-mail:
[email protected]. ORCID
Nikolaos I. Rousis: 0000-0003-0127-7899 Author Contributions §
Co-first authors.
Funding
Financial support by the SEWPROF Marie Curie ITN project “A new paradigm in drug use and human health risk assessment: Sewage profiling at the community level” (grant agreement 317205) supported by the European Union’s Seventh Framework Programme for research, technological development and demonstration is gratefully acknowledged. C
DOI: 10.1021/acs.est.8b01403 Environ. Sci. Technol. XXXX, XXX, XXX−XXX
