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Basic representation of the three major endocrine system axes mediated by hormonal signalling from the hypothalamus and anterior pituitary gland in the brain 

Basic representation of the three major endocrine system axes mediated by hormonal signalling from the hypothalamus and anterior pituitary gland in the brain 

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Globally, water resources are under constant threat of being polluted by a diverse range of man-made chemicals, and South Africa is no exception. These contaminants can have detrimental effects on both human and wildlife health. It is increasingly evident that several chemicals may modulate endocrine system pathways in vertebrate species, and these...

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... micro-pollutants, or emerging contaminants (ECs), found in environmental waters have been linked to potentially causing a large variety of health effects in both invertebrates and vertebrates (Daughton and Ternes, 1999;McKinlay et al., 2008;Bolong et al., 2009). In particular, selected pollutants have been suggested to interact with endocrine system pathways of vertebrates, and are collectively referred to as endocrine- disrupting contaminants (EDCs). The USEPA defines an EDC as: 'An exogenous agent that interferes with the synthesis, secretion, transport, binding, action, or elimination of natural hormones in the body that are responsible for the maintenance of homeostasis, reproduction, development, and/or behaviour' (USEPA, 1997). Man-made compounds most frequently impli- cated as EDCs include pesticides, pharmaceuticals, personal care products, and industrial by-products. Classic examples of environmental endocrine disruption include studies show- ing the feminisation of male fish and widespread occurrence of anti-androgenic ligands within UK rivers which receive effluent from connected WWTWs ( Liney et al., 2006;Jobling et al., 2009). Guillette and co-workers published a series of accounts confirming the disruption of the male reproductive system in juvenile male alligators in several lakes (especially Lake Apopka) situated within Florida, USA (Guillette et al., 1996;. Reproductive deformities, ranging from reduced penis size to altered plasma testosterone (T) levels were associ- ated with extensive agricultural use of the insecticide DDT and other persistent organic pollutants (POP) leading towards non- point source pollution in water systems flowing into the lakes ( Guillette et al., 1996;. Along with the concerns about the general disruption of human reproductive systems leading to various detrimental effects such as ovarian cancer, breast cancer and declined sperm quality, international concerns were voiced regarding the potential subtle disruption of the endocrine systems of humans and wildlife during the organisa- tional window during development ( Colborn et al. 1993). The documented reports on the occurrence of endocrine disruption within natural wildlife populations have raised international awareness of the harmful effects which man-made pollutants can exert on surface water quality for reuse. EDCs are known to modulate either one of the three major axes of the endocrine system, namely the hypothalamus-pitu- itary-gonad (HPG), hypothalamus-pituitary-thyroid (HPT), and hypothalamus-pituitary-adrenal (HPA) axes (Fig. 2). Within these pathways, several hormones, metabolic enzymes and receptors are responsible for the dispersal, activity and function of various physiological traits in vertebrates. Due to the vast cross-talk between endocrine system axes, disruption of a particular component within one endocrine axis may also cause modulation of other endocrine systems. It is therefore evident that a cocktail of EDCs present in the environment can have a range of negative effects on vertebrate health through modulating various endocrine system ...
Context 2
... from the regularly-prescribed antibiotic pharma- ceuticals detected in environmental waters, it is shown that compounds in personal care products can also have endocrine- disrupting properties. One of the most well documented compounds is the biocide triclosan (TCS), which is used as a disinfectant in soaps, detergents, toothpastes, mouthwash, and more (Raut and Angus, 2010). This compound also shows a high partition coefficient (K ow ) value (Log K ow 4.66; KOWWIN v. 1.67, EPI Suite), which indicates that TCS is highly lipid-soluble and does not readily dissolve in water. For this reason, TCS can be regarded as a POP, which can accumulate in the fat tissue of exposed organisms, and can also be transported in water bodies over great distances. This has been shown in a study demonstrating high levels of TCS in the breast milk of pregnant Swedish women (Allmyr et al., 2006). The pollution of TCS in the environment can therefore be assessed in a similar way to the exposure of organochloride insecticides in environmental waters, such as DDT and endosulfan, which are also shown to accumulate in the fat tissue of both wildlife and ...

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... To highlight the application of PMRs in the removal of ECs, the following section will focus on the removal of EDCs by PMRs. It is well-documented in the literature that EDCs and their metabolites are partially removed by standard WWTPs and can be quantified in water at concentrations of up to g.L −1 [55,[192][193][194]. Regardless of the concentration level, the presence of EDCs in water and continuous exposure raises several concerns due to their toxicological chronic consequences which remain unknown. ...
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... Endocrine disturbances. Both estrogenic and antiandrogenic effects [83]. ...
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... However, several recalcitrant pollutants and their associated metabolites (breakdown products) are indeed not completely removed within treatment systems before discharged into recipient environmental waters, or re-used for potable-and/or non-potable purposes. Causes for of such incomplete removal Apart from the potential toxicological risk and lethal effects which organic pollutants may pose upon wildlife and human health, it has become evident that several micro-pollutants such as pharmaceuticals, consumer products, pesticides and industrial by-products are also able to interact with endocrine systems, in one way or another, at concentrations regularly detected in surface waters (Archer et al., 2017b;Mckinlay et al., 2008). In particular, compounds interfering with gonadal endocrine system pathways have been of interest in surface water monitoring studies during the past few decades (Barnhoorn et al., 2004;Gracia et al., 2007;Guillette et al., 1996;Mckinlay et al., 2008;Mills et al., 2001;Lӧfgren et al., 2006). ...
... Estimating the exact source of estrogenicity within environmental samples may prove difficult, which was the reason why chemical analysis of known estrogenic micro-pollutants were not considered during the present study. Several pesticides, pharmaceuticals, personal care products and industrial by-products have been established as estrogenic EDCs (Archer et al., 2017b;Mckinlay et al., 2008). However, estrogenicity within waste-and surface waters are primarily attributed to the presence of synthetic-and natural estrogen hormones (Tanaka et al., 2001), merely due to such steroid hormones being more potent ER agonists than the estrogenmimicking EDCs. ...
... Alarmingly, the estimated EEQs from the downstream river sample was higher than EEQs estimated for WWTW2 effluent during the summer 2015/16 sampling campaign (APPENDIX Table A1). We previously reported similar results for this river, showing an extensive list of pharmaceuticals and personal care products at higher concentrations in downstream river water compared to treated wastewater discharge (Archer et al., 2017b). The same trend was shown in the current study for WWTW1, 3, 6, 7 and 9 during summer 2015/16, and WWTW1, 3, 6 and 9 during winter 2016 sampling. ...
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... From an African perspective, many communities including those in urban areas do not have access to proper sanitation facilities, leading to direct release of excreta and sewerage into surface water bodies (Madikizela et al., 2017). As a result, much higher concentrations of pharmaceuticals in the environment have been reported for Africa compared with Europe (Archer et al., 2017;Faleye et al., 2018;Fekadu et al., 2019). In addition, various other point sources of pharmaceuticals common in developing countries such as dumpsites, seepages from septic tanks, landfill leachates, and WWTP sludge used for fertilizer have been reported in the literature (Madikizela et al., 2017;Patel et al., 2019;Philip et al., 2018). ...
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... In addition, various other point sources of pharmaceuticals common in developing countries such as dumpsites, septic tank leakage, landfill leachates, and WWTP sludge used for fertilizer have been reported in literature (Madikizela et al., 2017;Philip et al., 2018;Patel et al., 2019). As a result, much higher concentrations of pharmaceuticals have been reported for Africa compared to Europe (Archer et al., 2017;Faleye et al., 2018;Fekadu et al., 2019;Offiong et al., 2019). ...
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One of the major concerns in the consumption of antibiotics is the discovery of antibacterial resistant genes due to prolonged exposure which makes their presence in environmental samples a priority. In this study, we screened 52 antibiotics along a South African stream polluted with wastewater effluents and municipal dumpsite leachates. Of these antibiotics, 15 were detected in the stream while 3 sulfonamides (sulfamethizole, sulfamethazine, sulfamethoxazole), a fluoroquinolone (flumequine) and a diaminopyrimidine (trimethoprim) were further quantified. The concentrations of sulfamethizole, sulfamethazine, sulfamethoxazole ranged from not detected to 0.133 µg L−1, flumequine ranged from 0.222 to 0.686 µg L−1, while trimethoprim was up to 0.0618 µg L−1. The highest concentrations were recorded at the point source discharge with most antibiotics not detected further downstream. The current study has further confirmed wastewater effluents and dumpsite leachates as pathways of antibiotics into the environment. Only the persistent unsanctioned antibiotic, flumequine had its risk quotient above 0.1 making it an antibiotic of environmental concern. Multiresidue studies are still limited in Africa and the current study offers a platform for a research paradigm shift with more studies expected to emerge providing an improved overview of the release of antibiotics and other pharmaceuticals into Africa’s vulnerable surface water systems.
... However, the information regarding the presence and fate of CECs during wastewater treatment and in freshwater ecosystems is limited for the African continent due to the lack of routine surveillance studies. Although most water monitoring studies on the African continent has been done in South Africa, it is still only restricted to a few regions of the country (Archer et al., 2017b;Madikizela et al., 2019). South Africa is a water-scarce, semi-arid country that experiences regular droughts and variable rainfall patterns that impact the availability of surface water resources, which is exacerbated by contamination due to aging infrastructure that does not keep up with the pace of population growth and associated expansion of industrial-and agricultural activity. ...
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... Fourteen (14) of these have been selected based on top 50 medicines utilized in the last published Malaysian Statistic of Medicine 2011-2014 report [49] i.e. amlodipine (AML), gliclazide (GLI), metformin (MEF), simvastatin (SIM), atenolol (ATE), acetylsalicylic acid (ASA), metoprolol (MET), acetaminophen (ACE), cetirizine (CET), salbutamol (SAL), chlorphenamine (CHL), ranitidine (RAN), diclofenac (DIC) and prazosin (PRA). The other three (3) compounds i.e. caffeine (CAF), carbamazepine (CBZ) and ibuprofen (IBU) have been selected based on previous high frequency detection in Southeast Asian environment water samples [27,28,50] as well as in other countries [34,[51][52][53]. A few of the pharmaceuticals selected in this study are also classified as over-the-counter (OTC) medicines in Malaysia, such as ACE and ASA, while some have been reported as having potential to be endocrine disruptors, such as DIC [21] and MEF [22]. ...
... The presence of GLI has been reported by Al-Odaini et al. and Al-Qaim et al. in Malaysian rivers with maximum amounts of 19.7 ng/L and 36 ng/L, respectively [27,99]. A comparable amount of GLI (53.9 ng/L) has been reported by Archer et al. in South Africa [51]. ...
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This review focuses on the occurrence and distribution of 17 targeted human pharmaceutical compounds from the most common therapeutic classes. These include one analgesic (acetaminophen), three non-steroidal anti-inflammatory drugs (NSAIDs) (acetylsalicylic acid, diclofenac, ibuprofen), two antidiabetic drugs (gliclazide, metformin), three antihistamines (cetirizine, chlorphenamine, ranitidine), four antihypertensives (amlodipine, atenolol, metoprolol, prazosin), one lipid regulator (simvastatin), one anti-convulsant (carbamazepine), one bronchodilator agent (salbutamol) and one stimulant (caffeine) which have been detected globally in various aquatic environmental matrices such as surface water, drinking water, ground water, seawater, influent and effluent of municipal wastewater treatment plants (WWTPs), hospital and industrial treatment plants, among others. The most common analytical method used involved solid phase extraction (SPE) and liquid chromatography coupled to mass spectrometry. The concentrations of all drugs investigated in all aqueous matrices varied from 0.5 to 85,000 ng/L for the highest concentration in the aqueous matrices in Southeast Asia. This review provides the first compilation on human pharmaceuticals in Southeast Asia in surface water, domestic wastewater (influent and effluent) and drinking water.
... The ecotoxicity of PPCP compounds remains one of the biggest knowledge gaps in PPCP research. While numerous studies regarding the toxic properties, lethal effects, and endocrine-disrupting potentials of PPCP compounds have been carried out globally, there are no generic conclusions regarding the negative effects of PPCPs that is applicable on all organisms [112][113][114][115][116][117][118][119]. Pharmaceuticals can have beneficial effects on humans, but these compounds can have adverse effects on non-target organisms exposed even at low concentrations. ...
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... 9 Many of the PPCPs [10][11][12] including SSRIs 4, [13][14][15][16] have been reported to induce adverse physiological effects on aquatic organisms, e.g., mortality, developmental and reproductive disorder, and endocrine disruption. 17,18 Moreover, drinking water quality may also be affected from the use of PPCP contaminated surface water that are used as an intake source for drinking water treatment plants (DWTPs). [19][20][21] This warrants incorporation of advanced treatment technologies i.e., adsorption and advanced oxidation processes (AOPs) into WWTPs and DWTPs for the effective removal of these recalcitrant PPCPs including SSRIs. ...
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Engineered nanomaterials, like graphene with tunable adsorption sites and nanoscale zero-valent iron (nZVI) with unique redox chemistry, offer great prospect for removing pharmaceutical and personal care products (PPCPs) through adsorption and catalytic advanced oxidation process (AOP) in comparison to bulk materials. Although PPCPs are found to be as a complex mixture in wastewater and in the environment, most studies regarding nano-enabled PPCP removal reported results with only one PPCP at a time and typically at high initial concentrations. In this study, we utilized reduced graphene oxide (rGO) to support nZVI to synthesize rGO-nZVI nanohybrid (NH) and used rGO-nZVI NH for the removal of a complex mixture of 12 diverse PPCPs that includes antibiotic, anti-inflammatory, anti-seizure, and antidepressant pharmaceuticals, and are recalcitrant in the environment. We also tested the removal of PPCPs at their individual environmentally relevant concentrations at ppb level. The rGO-nZVI NH synergistically performed as both an adsorbent and a heterogeneous Fenton catalyst (for AOP) in the presence of H2O2, to remove ~95-99% of environmentally relevant concentrations (200 ppb) of the PPCPs within 10 minutes. Even in the absence of H2O2, the hybridization resulted in better adsorptive property (14-72% more removal) in the rGO-nZVI NH compared to the parent nanomaterials (rGO or nZVI) for various PPCPs in the mixture, removing ~82-99% of the PPCPs, at the end of 30 minutes, with comparatively slower kinetics (~3-5.5 times) than in presence of H2O2. Hydrophobic PPCPs were removed faster and more with both the adsorption and AOP. The potential of utilizing rGO-nZVI NH in drinking/wastewater treatment system, or even in point-of-use system where necessary, was substantiated by the enhanced and fast PPCP removal capacity of the nanohybrid.
... Apart from the potential lethal toxicity risk that organic pollutants may pose upon wildlife and human health, it has become evident that several micro-pollutant are also able to modulate physiological pathways such as endocrine system pathways in one way or another at concentrations regularly detected in surface waters (Archer et al., 2017b). Compounds that interfere with gonadal endocrine system pathways have been the major point of interest (Jia et al., 2019;Sabir et al., 2019) where the presence of such endocrine-disrupting contaminants (EDCs) in surface waters have been proposed to contribute towards various noncommunicable diseases and developmental/reproductive disorders (Soto and Sonnenschein, 2010;Zarean and Poursafa, 2019). ...
... As mentioned before, some phenols, phthalates and pesticides at the mg/L level has been recorded previously in the province where the current study was done that originated from industrial runoff sources (Mahomed et al., 2008). Moreover, levels of phthalates have also been detected at concentrations reaching mg/L levels in South African surface waters (Fatoki et al., 2008), along with various pharmaceuticals and personal care products (PPCPs) of which many have been shown as potential EDCs (Archer et al., 2017b). These studies points to the potential of both known-and unknown estrogen agonists that can exert an additive mixture effect towards a net estrogenic response in bioassays such as the YES. ...
... As expected, nearly all of the EEQ estimates of raw influent WWTW samples were either above the 5 or 10 ng/L level (Tables S1 and S2), as several micro-pollutants are known to mimic an estrogen response similar to E 2 (Archer et al., 2017b;Mckinlay et al., 2008). For treated effluent wastewater, none of the sampling sites showed levels above the proposed LOEC of 10 ng/L and only EEQ estimations for WWTW-9 were above the 5 ng/L level during the summer 2015/16 sampling, and WWTW-8 EEQs close to this level during the winter 2016 sampling ( Fig. 4; Table S1) e both of which showed low EEQ mass balance reduction during the respective sampling campaigns (Table 2). ...