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I remember well a reviewer's comment regarding my first proposal to obtain funding for a project to determine whether pharmaceuticals were being discharged in municipal wastewater in Canada. The reviewer commented that, “pharmaceuticals are unlikely to be released into wastewater in amounts that pose a hazard to the environment or to human health.” To a certain extent, 15 yr later, we are still struggling to address the validity of this comment. Through the cooperation and mentorship of my colleague, Thomas Ternes, our early work showed that several pharmaceuticals were present at detectable concentrations in both untreated and treated wastewater from Canadian municipal wastewater treatment plants (WWTPs) [1]. A widely studied article by McAvoy et al. [2] published in Environmental Toxicology and Chemistry was one of the first to demonstrate that the personal care product triclosan is discharged from municipal WWTPs. We also showed that the residues of several pharmaceuticals are present in surface waters near urban centers in the Great Lakes [3]. Subsequent studies by Canadian researchers have shown that pharmaceuticals and personal care products (PPCPs) make their way into drinking water as a result of upstream discharges from WWTPs [4-6]. Finally, studies conducted in Canada have demonstrated that PPCPs in municipal biosolids that are applied to agricultural soils can be transported by overland flow into surface water or by percolation into tile water [7].

It is now clear that many different classes of down-the-drain chemicals discharged in domestic sewage can pass through municipal WWTPs and can then be released into aquatic and terrestrial environments. Several research, monitoring, and regulatory trends can be traced to this issue. First, agencies responsible for monitoring the levels of contaminants in the environment are struggling to implement monitoring programs for an ever-expanding range of PPCPs and endocrine disruptor compounds (EDCs). Such chemicals add to the growing list of current-use pesticides and persistent contaminants of emerging concern (e.g., brominated flame retardants, perfluorinated substances), as well as legacy contaminants still present in our environment. Remarkable advances have been made in developing analytical techniques for PPCPs, primarily using liquid chromatography with tandem mass spectrometry (LC-MS/MS) instrumentation [8]. The list of target PPCPs has increased to several dozens of compounds, including, in some cases, drug metabolites. To reduce analytical effort and simplify the interpretation of monitoring data, there is a recent trend to focus on a smaller number of indicator compounds in wastewater [9] or to analyze recalcitrant compounds, such as artificial sweeteners, as tracers of wastewater contamination [10].

The regulatory response to the issue of PPCPs in the environment has been variable, depending on the regulatory jurisdiction. The European Union (EU) developed specific ecological risk assessment procedures for new human pharmaceuticals appearing on the market [11]. Although these EU regulations specify that negative ecological risk assessments cannot be the basis for nonapproval of new drugs, the regulations include the option to apply risk management procedures to reduce the potential for environmental impacts. In the United States and in Canada, ecological risk assessments for pharmaceuticals are conducted in much the same way as risk assessments for other classes of chemicals appearing on the market, although new regulations may be developed soon.

Research focusing on the issue of PPCPs in the environment has shifted to linking biological effects to exposure. Risk assessments for exposure of humans to pharmaceuticals in drinking water have generally concluded that exposure to nanograms per liter concentrations would fall well below acceptable daily intakes, although these assessment methods have been challenged [12]. Considerable work has been done on antibacterial resistance in microorganisms exposed to antibiotics in the environment [13], and this remains an area of concern. Much of the early work on effects in aquatic and terrestrial organisms has shifted from evaluating acute toxicity (i.e., mortality), which generally occurs at concentrations that are not environmentally relevant, to studies of sublethal biological effects that occur at much lower concentrations. Recent exposure assessments, therefore, have tended to focus on evaluating mixtures of pharmaceuticals that are mechanistically linked, or in some cases, mixtures of chemicals from different classes that may cause drug–drug interactions. Figure 1, for example, shows total concentrations of antidepressants and their biologically active metabolites detected in river water downstream of a WWTP [14] that are within the range of concentrations of the antidepressant fluoxetine that induce effects on reproductive and endocrine endpoints in fish [15-17].

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Figure 1. Mean total concentrations (µg/L) of antidepressants detected upstream and downstream of a wastewater treatment plant (WWTP) discharging into the Grand River, Ontario, Canada [14] compared to the lowest observed effect concentrations (LOECs) for sublethal responses to fluoxetine in fish species [15-17].

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These types of studies, which relate exposures to effects for mixtures of PPCPs, are likely to be active areas for future research. It will be difficult, however, to develop regulatory approaches for reducing the impacts of exposure to mixtures of these chemicals.

REFERENCES

  1. Top of page
  2. SUPPLEMENTAL DATA
  3. REFERENCES
  4. Supporting Information
  • 1
    Metcalfe CD, Koenig BG, Bennie DT, Servos M, Ternes TA, Hirsch R. 2003. Occurrence of acidic and neutral drugs in the effluents of Canadian sewage treatment plants. Environ Toxicol Chem 22:28722880.
  • 2
    McAvoy DC, Schatowitz B, Jacob M, Hauk A, Eckhoff WS. 2002. Measurement of triclosan in wastewater treatment systems. Environ Toxicol Chem 21:13231329.
  • 3
    Metcalfe CD, Miao X-S, Koenig BG, Struger J. 2003. Distribution of acidic and neutral drugs in surface waters near sewage treatment plants in the lower Great Lakes, Canada. Environ Toxicol Chem 22:28812889.
  • 4
    Servos MR, Smith M, McInnis R, Burnison K, Lee H-B, Seto P, Backus S. 2007. The presence of selected pharmaceuticals and the antimicrobial triclosan in drinking water in Ontario, Canada. Water Qual Res J Canada 42:130137.
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    Garcia-Ac A, Segura PA, Viglino L, Furtos A, Gagnon C, Prevost M, Sauvé S. 2009. On-line solid phase extraction of large-volume injections coupled to liquid chromatography–tandem mass spectrometry for the quantitation and confirmation of 14 selected trace organic contaminants in drinking and surface water. J Chromatogr A 1216:85188527.
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    Kleywegt S, Pileggi V, Yang P, Hao C, Zhao X, Rocks C, Thach S, Cheung P, Whitehead B. 2011. Pharmaceuticals, hormones and bisphenol A in untreated source and finished drinking water in Ontario, Canada–Occurrence and treatment efficiency. Sci Total Environ 409:14811488.
  • 7
    Topp E, Metcalfe CD, Boxall ABA, Lapen DR. 2010. Transport of PPCPs and veterinary medicines from agricultural fields following application of biosolids and manure. In Halden R, ed, Contaminants of Emerging Concern in the Environment: Ecological and Human Health Considerations. ACS Symposium Series, American Chemical Society, Washington, DC, pp 227240.
  • 8
    Richardson SD, Ternes TA. 2011. Water analysis: Emerging contaminants and current issues. Anal Chem 83:46144648.
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    Dickenson ERV, Snyder SA, Sedlak DL, Drewes JE. 2011. Indicator compounds for assessment of wastewater effluent contributions to flow and water quality. Water Res 45:11991212.
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    Mawhinney DB, Young RB, Vanderford BJ, Borsch T, Snyder SA. 2011. Artificial sweetener sucralose in US drinking water systems. Environ Sci Technol 45:87168722.
  • 11
    Koschorreck J, Kickmann S. 2008. European developments in the environmental risk assessment of pharmaceuticals. In Kümmerer K, ed, Pharmaceuticals in the Environment: Sources, Fate, Effects and Risks, 3rd ed. Springer-Verlag, Berlin, Heidelberg, Germany, pp 324334.
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    Bachman Ducey S, Sapkota A. 2010. Presence of pharmaceuticals and personal care products in the environment–A concern for human health? In Halden R, ed, Contaminants of Emerging Concern in the Environment: Ecological and Human Health Considerations. ACS Symposium Series, American Chemical Society, Washington, DC, pp 346365.
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    Kümmerer K. 2004. Resistance in the environment. In Kümmerer K, ed, Pharmaceuticals in the Environment: Sources, Fate, Effects and Risks, 2nd ed. Springer-Verlag, Berlin, Heidelberg, Germany, pp 223231.
  • 14
    Metcalfe CD, Chu S, Judt C, Li H, Oakes KD, Servos MR, Andrews DM. 2010. Antidepressants and their metabolites in municipal wastewater, and downstream exposure in an urban watershed. Environ Toxicol Chem 29:7989.
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    Lister A, Regan C, Van Zwol J, Van Der Kraak G. 2009. Inhibition of egg production in zebrafish by fluoxetine and municipal effluents: A mechanistic evaluation. Aquatic Toxicol 95:320329.
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    Mennigen JA, Lado WE, Zamora JM, Duarte-Guterman P, Langlois VS, Metcalfe CD, Chang JP, Moon TW, Trudeau VL. Waterborne fluoxetine disrupts the reproductive axis in sexually mature male goldfish, Carassius auratus. Aquatic Toxicol 100:354364.
  • 17
    Schultz MM, Painter MM, Bartell AW, Logue A, Furlong ET, Werner SL, Schoenfuss HL. 2011. Selective uptake and biological consequences of environmentally relevant antidepressant pharmaceutical exposures on male fathead minnows. Aquatic Toxicol 104:3847.

Supporting Information

  1. Top of page
  2. SUPPLEMENTAL DATA
  3. REFERENCES
  4. Supporting Information

All Supplemental Data may be found in the online version of this article.

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Table 1. Ranking by citation frequency of the top 100 (102) papers published in Environmental Toxicology and Chemistry

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