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The high throughput screening of chemicals for interaction with intracellular targets is gaining prominence in the toxicity evaluation of environmental chemicals. We describe ligand-mediated receptor assembly as an early event in receptor signaling and its application to the screening of chemicals for interaction with targeted receptors. We utilized bioluminescence resonance energy transfer (BRET) to detect and quantify assembly of the methyl farnesoate receptor (MfR) in response to various high-production volume and other chemicals. The hormone methyl farnesoate binds to the MfR to regulate various aspects of reproduction and development in crustaceans. The MfR protein subunits Met and SRC, cloned from Daphnia pulex, were fused to the fluorophore, mAmetrine and the photon generator, Rluc2, respectively. Ligand-mediated receptor assembly was measured by photon transfer from the photon donor to the fluorophore resulting in fluorescence emission. Overall, the BRET assay had comparable or greater sensitivity as compared to a traditional reporter gene assay. Further, chemicals that screened positive in the BRET assay also stimulated phenotypic outcomes in daphnids that result from MfR signaling. We concluded the BRET assay is an accurate, sensitive, and cost/time efficient alternative to traditional screening assays.
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Daphnia , Genes Reporter , Ligantes , Poluentes Químicos da Água/toxicidade , Animais , Transferência de Energia , Reprodução , Testes de ToxicidadeRESUMO
The protection and management of water resources continues to be challenged by multiple and ongoing factors such as shifts in demographic, social, economic, and public health requirements. Physical limitations placed on access to potable supplies include natural and human-caused factors such as aquifer depletion, aging infrastructure, saltwater intrusion, floods, and drought. These factors, although varying in magnitude, spatial extent, and timing, can exacerbate the potential for contaminants of concern (CECs) to be present in sources of drinking water, infrastructure, premise plumbing and associated tap water. This monograph examines how current and emerging scientific efforts and technologies increase our understanding of the range of CECs and drinking water issues facing current and future populations. It is not intended to be read in one sitting, but is instead a starting point for scientists wanting to learn more about the issues surrounding CECs. This text discusses the topical evolution CECs over time (Section 1), improvements in measuring chemical and microbial CECs, through both analysis of concentration and toxicity (Section 2) and modeling CEC exposure and fate (Section 3), forms of treatment effective at removing chemical and microbial CECs (Section 4), and potential for human health impacts from exposure to CECs (Section 5). The paper concludes with how changes to water quantity, both scarcity and surpluses, could affect water quality (Section 6). Taken together, these sections document the past 25 years of CEC research and the regulatory response to these contaminants, the current work to identify and monitor CECs and mitigate exposure, and the challenges facing the future.
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BACKGROUND: Bottled water (BW) consumption in the United States and globally has increased amidst heightened concern about environmental contaminant exposures and health risks in drinking water supplies, despite a paucity of directly comparable, environmentally-relevant contaminant exposure data for BW. This study provides insight into exposures and cumulative risks to human health from inorganic/organic/microbial contaminants in BW. METHODS: BW from 30 total domestic US (23) and imported (7) sources, including purified tapwater (7) and spring water (23), were analyzed for 3 field parameters, 53 inorganics, 465 organics, 14 microbial metrics, and in vitro estrogen receptor (ER) bioactivity. Health-benchmark-weighted cumulative hazard indices and ratios of organic-contaminant in vitro exposure-activity cutoffs were assessed for detected regulated and unregulated inorganic and organic contaminants. RESULTS: 48 inorganics and 45 organics were detected in sampled BW. No enforceable chemical quality standards were exceeded, but several inorganic and organic contaminants with maximum contaminant level goal(s) (MCLG) of zero (no known safe level of exposure to vulnerable sub-populations) were detected. Among these, arsenic, lead, and uranium were detected in 67 %, 17 %, and 57 % of BW, respectively, almost exclusively in spring-sourced samples not treated by advanced filtration. Organic MCLG exceedances included frequent detections of disinfection byproducts (DBP) in tapwater-sourced BW and sporadic detections of DBP and volatile organic chemicals in BW sourced from tapwater and springs. Precautionary health-based screening levels were exceeded frequently and attributed primarily to DBP in tapwater-sourced BW and co-occurring inorganic and organic contaminants in spring-sourced BW. CONCLUSION: The results indicate that simultaneous exposures to multiple drinking-water contaminants of potential human-health concern are common in BW. Improved understandings of human exposures based on more environmentally realistic and directly comparable point-of-use exposure characterizations, like this BW study, are essential to public health because drinking water is a biological necessity and, consequently, a high-vulnerability vector for human contaminant exposures.
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Água Potável , Compostos Orgânicos Voláteis , Poluentes Químicos da Água , Humanos , Estados Unidos , Abastecimento de Água , Exposição Ambiental/efeitos adversos , Poluentes Químicos da Água/análiseRESUMO
In the United States and globally, contaminant exposure in unregulated private-well point-of-use tapwater (TW) is a recognized public-health data gap and an obstacle to both risk-management and homeowner decision making. To help address the lack of data on broad contaminant exposures in private-well TW from hydrologically-vulnerable (alluvial, karst) aquifers in agriculturally-intensive landscapes, samples were collected in 2018-2019 from 47 northeast Iowa farms and analyzed for 35 inorganics, 437 unique organics, 5 in vitro bioassays, and 11 microbial assays. Twenty-six inorganics and 51 organics, dominated by pesticides and related transformation products (35 herbicide-, 5 insecticide-, and 2 fungicide-related), were observed in TW. Heterotrophic bacteria detections were near ubiquitous (94 % of the samples), with detection of total coliform bacteria in 28 % of the samples and growth on at least one putative-pathogen selective media across all TW samples. Health-based hazard index screening levels were exceeded frequently in private-well TW and attributed primarily to inorganics (nitrate, uranium). Results support incorporation of residential treatment systems to protect against contaminant exposure and the need for increased monitoring of rural private-well homes. Continued assessment of unmonitored and unregulated private-supply TW is needed to model contaminant exposures and human-health risks.
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Água Potável , Água Subterrânea , Poluentes Químicos da Água , Estados Unidos , Humanos , Iowa , Poluentes Químicos da Água/análise , Agricultura , Monitoramento Ambiental/métodosRESUMO
In the United States (US), private-supply tapwater (TW) is rarely monitored. This data gap undermines individual/community risk-management decision-making, leading to an increased probability of unrecognized contaminant exposures in rural and remote locations that rely on private wells. We assessed point-of-use (POU) TW in three northern plains Tribal Nations, where ongoing TW arsenic (As) interventions include expansion of small community water systems and POU adsorptive-media treatment for Strong Heart Water Study participants. Samples from 34 private-well and 22 public-supply sites were analyzed for 476 organics, 34 inorganics, and 3 in vitro bioactivities. 63 organics and 30 inorganics were detected. Arsenic, uranium (U), and lead (Pb) were detected in 54%, 43%, and 20% of samples, respectively. Concentrations equivalent to public-supply maximum contaminant level(s) (MCL) were exceeded only in untreated private-well samples (As 47%, U 3%). Precautionary health-based screening levels were exceeded frequently, due to inorganics in private supplies and chlorine-based disinfection byproducts in public supplies. The results indicate that simultaneous exposures to co-occurring TW contaminants are common, warranting consideration of expanded source, point-of-entry, or POU treatment(s). This study illustrates the importance of increased monitoring of private-well TW, employing a broad, environmentally informative analytical scope, to reduce the risks of unrecognized contaminant exposures.
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BACKGROUND: Humans are primary drivers of environmental contamination worldwide, including in drinking-water resources. In the United States (US), federal and state agencies regulate and monitor public-supply drinking water while private-supply monitoring is rare; the current lack of directly comparable information on contaminant-mixture exposures and risks between private- and public-supplies undermines tapwater (TW) consumer decision-making. METHODS: We compared private- and public-supply residential point-of-use TW at Cape Cod, Massachusetts, where both supplies share the same groundwater source. TW from 10 private- and 10 public-supply homes was analyzed for 487 organic, 38 inorganic, 8 microbial indicators, and 3 in vitro bioactivities. Concentrations were compared to existing protective health-based benchmarks, and aggregated Hazard Indices (HI) of regulated and unregulated TW contaminants were calculated along with ratios of in vitro exposure-activity cutoffs. RESULTS: Seventy organic and 28 inorganic constituents were detected in TW. Median detections were comparable, but median cumulative concentrations were substantially higher in public supply due to 6 chlorine-disinfected samples characterized by disinfection byproducts and corresponding lower heterotrophic plate counts. Public-supply applicable maximum contaminant (nitrate) and treatment action (lead and copper) levels were exceeded in private-supply TW samples only. Exceedances of health-based HI screening levels of concern were common to both TW supplies. DISCUSSION: These Cape Cod results indicate comparable cumulative human-health concerns from contaminant exposures in private- and public-supply TW in a shared source-water setting. Importantly, although this study's analytical coverage exceeds that currently feasible for water purveyors or homeowners, it nevertheless is a substantial underestimation of the full breadth of contaminant mixtures documented in the environment and potentially present in drinking water. CONCLUSION: Regardless of the supply, increased public engagement in source-water protection and drinking-water treatment, including consumer point-of-use treatment, is warranted to reduce risks associated with long-term TW contaminant exposures, especially in vulnerable populations.
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Água Subterrânea , Poluentes Químicos da Água , Purificação da Água , Monitoramento Ambiental , Humanos , Massachusetts , Estados Unidos , Água , Poluentes Químicos da Água/análise , Abastecimento de ÁguaRESUMO
Although endocrine disrupting compounds have been detected in wastewater and surface waters worldwide using a variety of in vitro effects-based screening tools, e.g. bioassays, few have examined potential attenuation of environmental contaminants by both natural (sorption, degradation, etc.) and anthropogenic (water treatment practices) processes. This study used several bioassays and quantitative chemical analyses to assess residence-time weighted samples at six sites along a river in the northeastern United States beginning upstream from a wastewater treatment plant outfall and proceeding downstream along the stream reach to a drinking water treatment plant. Known steroidal estrogens were quantified and changes in signaling pathway molecular initiating events (activation of estrogen, androgen, glucocorticoid, peroxisome proliferator-activated, pregnane X receptor, and aryl hydrocarbon receptor signaling networks) were identified in water extracts. In initial multi-endpoint assays geographic and receptor-specific endocrine activity patterns in transcription factor signatures and nuclear receptor activation were discovered. In subsequent single endpoint receptor-specific bioassays, estrogen (16 of 18 samples; 0.01 to 28â¯ng estradiol equivalents [E2Eqs]/L) glucocorticoid (3 of 18 samples; 1.8 to 21â¯ng dexamethasone equivalents [DexEqs]/L), and androgen (2 of 18 samples; 0.95 to 2.1â¯ng dihydrotestosterone equivalents [DHTEqs]/L) receptor transcriptional activation occurred above respective assay method detection limits (0.04â¯ng E2Eqs/L, 1.2â¯ng DexEqs/L, and 0.77â¯ng DHTEqs/L) in multiple sampling events. Estrogen activity, the most often detected, correlated well with measured concentrations of known steroidal estrogens (r2â¯=â¯0.890). Overall, activity indicative of multiple types of endocrine active compounds was highest in wastewater effluent samples, while activity downstream was progressively lower, and negligible in unfinished treated drinking water. Not only was estrogenic and glucocorticoid activity confirmed in the effluent by utilizing multiple methods concurrently, but other activated signaling networks that historically received less attention (i.e. peroxisome proliferator-activated receptor) were also detected.