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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    • "In a national pilot study on the occurrence of pharmaceuticals and personal care products in fish tissues collected from effluent-dominated rivers in the United States, Ramirez et al.[1]reported detection of the following compounds: antidepressants (norfluoxetine, sertraline), antihistamine (diphenhydramine), antihypertension (diltiazem), antiseizure (carbamazapine), antimicrobial (triclosan), and fragrances (galaxolide, tonalide). Several reports on prioritizing or ranking pharmaceuticals that may pose a potential threat to the environment are available in the literature2345678910. In a 2008 study[11], a preliminary environmental risk assessment database consisting of the top 200 prescription drugs identified cardiovascular and neuroactive compounds (in addition to antibiotics) as high-risk therapeutic classes. "
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    ABSTRACT: The present study examined the bioconcentration of 2 basic pharmaceuticals: verapamil (a calcium channel blocker) and clozapine (an antipsychotic compound) in 2 fresh water fishes, fathead minnow and channel catfish. In 4 separate bioconcentration factor (BCF) experiments (2 chemicals × 1 exposure concentration × 2 fishes), fathead minnow and channel catfish were exposed to 190 µg/L and 419 µg/L of verapamil (500 µg/L nominal) or 28.5 µg/L and 40 µg/L of clozapine (50 µg/L nominal), respectively. Bioconcentration factor experiments with fathead consisted of 28 d uptake and 14 d depuration, whereas tests conducted on catfish involved a minimized test design, with 7 d each of uptake and depuration. Fish (n = 4–5) were sampled during exposure and depuration to collect different tissues: muscle, liver, gills, kidneys, heart (verapamil tests only), brain (clozapine tests only), and blood plasma (catfish tests only). Verapamil and clozapine concentrations in various tissues of fathead and catfish were analyzed using liquid chromatography–mass spectrometry. In general, higher accumulation rates of the test compounds were observed in tissues with higher perfusion rates. Accumulation was also high in tissues relevant to pharmacological targets in mammals (i.e. heart in verapamil test and brain) in the clozapine test. Tissue-specific BCFs (wet weight basis) for verapamil and clozapine ranged from 0.7 to 75 and from 31 to 1226, respectively. Tissue-specific concentration data were used to examine tissue–blood partition coefficients. This article is protected by copyright. All rights reserved
    Full-text · Article · Jan 2016 · Environmental Toxicology and Chemistry
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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.
    Full-text · Article · Sep 2015 · Human and Ecological Risk Assessment
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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.
    Full-text · Article · Mar 2015 · Environmental Pollution
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