Pharmaceutical contaminants of emerging concern in the environment

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]. 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.