Human pharmaceuticals in US surface waters: a human health risk assessment. Regul Toxicol Pharmacol

Eli Lilly, Indianapolis, Indiana, United States
Regulatory Toxicology and Pharmacology (Impact Factor: 2.03). 09/2005; 42(3):296-312. DOI: 10.1016/j.yrtph.2005.05.005
Source: PubMed


The detection of low levels of pharmaceuticals in rivers and streams, drinking water, and groundwater has raised questions as to whether these levels may affect human health. This report presents human health risk assessments for 26 active pharmaceutical ingredients (APIs) and/or their metabolites, representing 14 different drug classes, for which environmental monitoring data are available for the United States. Acceptable daily intakes (ADIs) are derived using the considerable data that are available for APIs. The resulting ADIs are designed to protect potentially exposed populations, including sensitive sub-populations. The ADIs are then used to estimate predicted no effect concentrations (PNECs) for two sources of potential human exposure: drinking water and fish ingestion. The PNECs are compared to measured environmental concentrations (MECs) from the published literature and to maximum predicted environmental concentrations (PECs) generated using the PhATE model. The PhATE model predictions are made under conservative assumptions of low river flow and no depletion (i.e., no metabolism, no removal during wastewater or drinking water treatment, and no instream depletion). Ratios of MECs to PNECs are typically very low and consistent with PEC to PNEC ratios. For all 26 compounds, these low ratios indicate that no appreciable human health risk exists from the presence of trace concentrations of these APIs in surface water and drinking water.

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    • "Predicted environmental concentrations (PECs) generated by PhATE TM are based on average per capita human use of an API in the United States. This assumption would cause PhATE TM to underestimate exposure in areas where per capita use is higher than the national average (Schwab et al. 2005). Anderson et al. (2012) used the PhATE TM model to compare the predicted no-effect concentration (PNEC) of endocrine disruptors (17β-estradiol [E2], 17à -ethinyl estradiol [EE2], and estriol [E3]) to mean and low concentrations of the steroid estrogens across 12 U.S watersheds. "
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    ABSTRACT: The presence of detectable amounts of contaminants in treated sewage sludge (concentrations μg/kg – mg/kg) has led to concerns that land applications of biosolids may result in an accumulation of contaminants in the soil and their subsequent translocation through the food chain. Despite advances in wastewater management (e.g., anaerobic, thermophilic, and mesophilic digestion), many compounds and their metabolites remain intact following treatment. This review looks at the main risk factors relating to the occurrence of “classic” (persistent organic pollutants [POPs]) and emerging pollutants (pharmaceuticals and personal care products) in biosolids. Relevant EU legislation and risk assessment strategies for the control of emerging contaminants are also considered. Organic pollutants regulated under the Stockholm Convention on POPs along with PPCPs were identified as contaminants of concern based on the risk factors: persistence, bioaccumulation, and toxicity (PBT). PPCPs were recognized as being of particular concern as their high transformation/removal rates are compensated by their continuous introduction into the environment. This study highlights the growing concern in relation to emerging contaminants in biosolids and highlights risk assessment strategies that can be used to characterize potential human/environmental risks.
    Human and Ecological Risk Assessment 09/2015; 21(2):1-22. DOI:10.1080/10807039.2014.930295 · 1.10 Impact Factor
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    • "Despite the worldwide release and occurrence of pharmaceutical residues in the aquatic environment, little is still known about the long-term evaluation of concentrations, especially in groundwater . Many studies deal with concentrations in effluents from wastewater treatment plants (WWTP) (Ternes and Hirsch, 2000; Bueno et al., 2012; Loos et al., 2013; Kostich et al., 2014), surface water (Schwab et al., 2005; Sacher et al., 2008; Loos et al., 2009; Vulliet and Cren-Oliv e, 2011), and groundwater (Sacher et al., 2001; Loos et al., 2010; Maeng et al., 2011; L opez-Serna et al., 2013), although most of them address single sampling campaigns. Time series data related to groundwater have been scarcely published (Wolf et al., 2012; Zemann et al., 2014) despite the fact that they can contribute significantly to a better understanding of substance behavior and long-term threads. "
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    ABSTRACT: Sewage input into a karst aquifer via leaking sewers and cesspits was investigated over five years in an urbanized catchment. Of 66 samples, analyzed for 25 pharmaceuticals, 91% indicated detectable concentrations. The former standard iodinated X-ray contrast medium (ICM) diatrizoic acid was detected most frequently. Remarkably, it was found more frequently in groundwater (79%, median: 54 ng/l) than in wastewater (21%, 120 ng/l), which is supposed to be the only source in this area. In contrast, iopamidol, a possible substitute, spread over the aquifer during the investigation period whereas concentrations were two orders of magnitude higher in wastewater than in groundwater. Knowledge about changing application of pharmaceuticals thus is essential to assess urban impacts on aquifers, especially when applying mass balances. Since correlated concentrations provide conclusive evidence that, for this catchment, nitrate in groundwater rather comes from urban than from rural sources, ICM are considered useful tracers.
    Environmental Pollution 03/2015; 198. DOI:10.1016/j.envpol.2014.11.033 · 4.14 Impact Factor
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    • "However, the interest of the scientific community on the pharmaceutical has really grown during the two last decades due to their continuous increased use (consumption in France has been multiplied by 200 since the 80s (Dulio et al., 2009)) and to the evolution of analytical techniques that enough improved to allow quantifying the presence of these substances in waters, even at really low concentrations. Then numerous publications deal with the Measured Environmental Concentrations (MECs) of pharmaceuticals that have been detected with levels which can go from ng/L to μg/L in surface waters of Austria (Clara et al., 2004), Canada (Comeau et al., 2008), Finland (Lindqvist et al., 2005), France (Togola and Budzinski, 2008; Vystavna et al., 2012), Germany (Nödler et al., 2011; Ternes, 1998), Greece (Arditsoglou and Voutsa, 2008), Italy (Zuccato et al., 2005), India (Larsson et al., 2007), Japan (Nakada et al., 2008), Korea (Choi et al., 2008), Norway (Grund et al., 2008), Romania (Moldovan, 2006), Spain (Joss et al., 2006), Sweden (Bendz et al., 2005), Switzerland (Tauxe-Wuersch et al., 2005), Ukraine (Vystavna et al., 2012), USA (MacLeod et al., 2007), and Western Balkans (Terzić et al., 2008), … in groundwater (Barnes et al., 2008; Fram and Belitz, 2011; Lopez-Serna et al., 2013; Müller et al., 2011; Reh et al., 2013; Vulliet and Cren-Olivé, 2011, …), as well as in drinking and tap waters (Heberer, 2002; Kuster et al., 2008; Schwab et al., 2005; Vulliet and Cren-Olivé, 2011; Valcárcel et al., 2011; …). Nevertheless, due to the current analytical processes that are not able to measure all the pharmaceutical molecules, to the number and the variability of molecules that may enter the environment, to the high costs and the consumption of time to sample and analyze this molecules, and to the requirements of Commission Directive 93/67/EEC, 1993; Commission Regulation, 1488/94/EC, 1994 and Commission Directive 98/8/EC, 1998, models to calculate Predicted Environmental Concentrations (PECs) have been developed (Castiglioni et al., 2004; Henshel et al., 1997; Stuer-Lauridsen et al., 2000). "
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    ABSTRACT: Due to the current analytical processes that are not able to measure all the pharmaceutical molecules and to the high costs and the consumption of time to sample and analyze PhACs, models to calculate Predicted Environmental Concentrations (PECs) have been developed. However a comparison between MECs and PECs, taking into account the methods of calculations and peculiarly the parameters included in the calculation (consumption data, pharmacokinetic parameters, elimination rate in STPs and in the environment), is necessary to assess the validity of PECs. MEC variations of sixteen target PhACs [acetaminophen (ACE), amlodipine (AML), atenolol (ATE), caffeine (CAF), carbamazepine (CAR), doxycycline (DOX), epoxycarbamazepine (EPO), fluvoxamine (FLU), furosemide (FUR), hydrochlorothiazide (HYD), ifosfamide (IFO), losartan (LOS), pravastatin (PRA), progesterone (PROG), ramipril (RAM), trimetazidine (TRI)] have been evaluated during one hydrological cycle, from October 2011 to October 2012 and compared to PECs calculated by using an adaptation of the models proposed by Heberer and Feldmann (2005) and EMEA (2006). Comparison of PECs and MECS has been achieved for six molecules: ATE, CAR, DOX, FUR, HYD and PRA. DOX, FUR and HYD present differences between PECs and MECs on an annual basis but their temporal evolutions follow the same trends. PEC evaluation for these PhACs could then be possible but need some adjustments of consumption patterns, pharmacokinetic parameters and/or mechanisms of (bio)degradation. ATE, CAR and PRA are well modeled; PECs can then be used as reliable estimation of concentrations without any reserve.
    Environment international 12/2014; 73:10–21. DOI:10.1016/j.envint.2014.06.015 · 5.56 Impact Factor
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