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Pharmaceuticals and Personal Care Products (Ppcps) and Their Sublethal and Lethal Effects in Aquatic Organisms

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Pharmaceuticals and Personal Care Products (Ppcps) and Their Sublethal and Lethal Effects in Aquatic Organisms Environmental Reviews Pharmaceuticals and personal care products (PPCPs) and their sublethal and lethal effects in aquatic organisms Journal: Environmental Reviews Manuscript ID er-2020-0054.R2 Manuscript Type: Review Date Submitted by the 08-Dec-2020 Author: Complete List of Authors: Srain, Harveer; School for Resource and Environmental Studies, Dalhousie University Beazley, Karen; School for Resource and Environmental Studies, Dalhousie University, Walker, Tony;Draft Dalhousie University Faculty of Management, School for Resource and Environmental Studies, Suite 5010, 6100 University Avenue Is this manuscript invited for consideration in a Special Not applicable (regular submission) Issue? : Emerging contaminants, Pharmaceutical and personal care products Keyword: (PPCPs), Aquatic toxicity, Lethal and sublethal effects, Aquatic organisms © The Author(s) or their Institution(s) Page 1 of 115 Environmental Reviews Pharmaceuticals and personal care products (PPCPs) and their sublethal and lethal effects in aquatic organisms Harveer S. Srain, Karen F. Beazley, Tony R. Walker* School for Resource and Environmental Studies, Dalhousie University, Halifax, NS, Canada * Corresponding author: Tony R. Walker ([email protected]) Draft 1 © The Author(s) or their Institution(s) Environmental Reviews Page 2 of 115 Abstract Pharmaceutical and personal care products (PPCPs) include over-the-counter and prescription drugs, veterinary drugs, fragrances, and cosmetics. PPCPs have been detected in aquatic environments at low concentrations and are emerging as contaminants of concern. PPCPs are primarily released into aquatic environments via untreated sewage, wastewater treatment plants, landfill leachate and can affect aquatic life through persistence, bioaccumulation, and toxicity. However, there are limited reviews of lethal and sublethal effects of PPCP exposures on aquatic organisms. To understand PPCP toxicity on aquatic organisms, a literature review was conducted which identified aquatic organisms known to be affected by PPCPs; concentrations of PPCPs reported as producing sublethal and lethal effects in aquatic organisms; and research gaps on PPCP aquatic toxicity. Twelve PPCPs were selected from three seminal studies for review, including Draftbisphenol A, carbamazepine, erythromycin, fluoxetine, linear alkylbenzene sulfonate, metoprolol, naproxen, nonylphenol, ofloxacin, sertraline, sulfamethoxazole, and triclosan. Many aquatic species were affected by PPCPs at sublethal and lethal exposures, including sublethal effects at environmentally relevant concentrations. Because lethal effects were seldom observed at environmentally relevant concentrations, many studies considered PPCPs non-toxic. Few studies have compared effects of PPCPs on the same organisms for identical exposure parameters (time and concentration), resulting in wide variation in reported toxicity levels with limited consensus in the academic literature. Consensus in lethal concentrations was reported for Daphnia magna with 48 h exposure for bisphenol A and triclosan and Vibrio fischeri with 15 min exposure to carbamazepine. Environmentally relevant sublethal concentrations were higher than water quality guidelines developed for Canada and predicted no-effect concentrations derived globally. Species sensitivity distributions for some PPCPs show that aquatic species are affected lethally at environmentally relevant concentrations. More studies on indirect, and long-term ecological effects along with testing chronic toxicity of PPCPs at environmentally relevant concentrations, is 2 © The Author(s) or their Institution(s) Page 3 of 115 Environmental Reviews recommended. These will help guide future research to determine extent and magnitude of PPCP concentrations in aquatic environments and help inform management decisions to reduce sources of PPCPs into the environment. Future management requires effective monitoring strategies regarding use, disposal, occurrence, and impacts at different life cycle stages of PPCPs in the environment. Key words Emerging contaminants; Pharmaceuticals and personal care products (PPCPs); Aquatic organisms; Aquatic toxicity; Lethal and sublethal effects; Species sensitivity distributions (SSDs). Draft 3 © The Author(s) or their Institution(s) Environmental Reviews Page 4 of 115 Introduction Pharmaceuticals and personal care products (PPCPs) comprise numerous classes of chemicals. Pharmaceuticals include different categories of drugs such as antibiotics, antihypertensives, antiepileptics, anti-inflammatory drugs, and analgesics. PCPs include fragrances, moisturizers, lipsticks, shampoos, toothpastes, and detergents (Boxall et al. 2012; Bu et al. 2013; Zhang et al. 2017). They are extensively used by humans for personal health or cosmetic reasons, in agribusiness, and in veterinary medicine to boost growth or health of livestock (Nikolaou et al. 2007). With their release into the environment, PPCPs are emerging as contaminants of concern (Mcbride and Wyckoff 2002). Commercial development of liquid chromatography mass spectrometry has now made it possible to detect low levels of PPCPs in the environment (Hao et al. 2006). Moreover, there has been a shift in focus of environmental contaminant researchDraft from conventional priority pollutants (e.g., polychlorinated biphenyls and polycyclic aromatic hydrocarbons) to the so-called emerging contaminants (Erickson 2002; Field et al. 2006; Arp 2012). However, due to their relatively recent emergence, little is known about the lethal and sublethal effects of PPCPs, individually and as mixtures, on specific organisms and in aquatic environments. Risk of PPCPs in aquatic environments PPCPs are released into the aquatic environment through several pathways. Major pathways are from wastewater treatment plants (WWTPs) and landfill leaching (Daughton and Ternes 1999; Thomas and Hilton 2004). Hence, many PPCPs pass through WWTPs and enter aquatic ecosystems in the form of parent compounds, metabolites, and transformation products (Benotti and Brownawell 2009). Presence of PPCPs in aquatic environments and can affect aquatic life through persistence, bioaccumulation, and toxicity (World Health Organisation 2015). 4 © The Author(s) or their Institution(s) Page 5 of 115 Environmental Reviews Persistence - There is often incomplete removal of PPCPs by WWTPs, except when treated through advanced wastewater treatment processes (Snyder 2008). PPCPs thereby make their way into aquatic environments, posing a potential risk to aquatic organisms (Bu et al. 2013). Extensive use of PPCPs globally and the growing introduction of new PPCPs to the market, followed by inefficient removal by WWTPs are contributing to their continuous increase in the aquatic environment (Nikolaou et al. 2007; Aus der beek et al. 2016; Osorio et al. 2016). Many PPCPs are pseudo-persistent in aquatic environments because they are continuously being released at source, despite on-going environmental degradation processes such as biodegradation, photodegradation, and particulate sorption (Houtman et al. 2004; Richmond et al. 2017). Bioaccumulation - PPCPs and their metabolites have the potential for bioaccumulation in organisms at different trophic levels (Mackay and BarnthouseDraft 2010). Bioaccumulation is a process of contaminants entering into the food chain from all possible exposure routes (water, sediment, soil, air, or diet) and accumulating in biological tissues of aquatic organisms at higher concentrations than ambient water (Wang and Fisher 1999; Walker et al. 2013; Walker and Grant 2015). For example, Gambusia holbrooki (mosquito fish) bioaccumulated pharmaceuticals such as caffeine, diphenhydramine, diltiazem, carbamazepine, and ibuprofen by factors of 2, 16, 16, 1.4 and 28, respectively (Wang and Gardinali 2013). Triclocarban and triclosan, widely used antimicrobial agents in PCPs, were detected in algal samples collected downstream from WWTP effluents in Texas. The bioaccumulation factor for triclocarban and triclosan ranged from 1600-2700 and 900-2100, respectively (Coogan et al. 2007). Toxicity – Chronic toxicity (sublethal effects) of PPCPs arise from their ability to interfere with endocrine systems and disruption of homeostasis of aquatic organisms along with a host of other abnormalities (Fabbri and Franzellitti 2016; Ebele et al. 2017). Acute toxicity (lethal effects) of PPCPs occur when mortality in aquatic organisms is observed (Wilkinson et al. 2016). For example, Carassius 5 © The Author(s) or their Institution(s) Environmental Reviews Page 6 of 115 auratus exhibited a reduction in plasma testosterone by over 50% after exposure to waterborne gemfibrozil for 14 days (Mimeault et al. 2005). Further, interactions of PPCPs as mixtures led to toxic effects, even though individual PPCPs may have been present at low concentrations (Choi et al. 2008). For example, estradiol and 4-tert-nonylphenol synergistically induced production of vitellogenin protein in juvenile rainbow trout, although neither compound did so on its own (Thorpe et al. 2001). Overall, toxicity of PPCPs depends on factors such as sensitivity of exposed organisms, duration of exposure, contaminant concentrations, and developmental stage of organisms when exposure occurs. Exposure of non-target organisms to chronic trace levels of PPCPs at certain sensitive stages of development produces more observable abnormalities than acute exposures to high doses at the same life stages (Wilkinson et al. 2016). Draft Due to their persistence, bioaccumulation, and toxicity,
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