Increasing studies are examining per- and polyfluoroalkyl substances (PFAS) induced toxicity and resulting health outcomes, including epigenetic modifications (e.g., DNA methylation, histone ...modification, microRNA expression). We critically reviewed current evidence from human epidemiological, in vitro, and animal studies, including mammalian and aquatic model organisms. Epidemiological studies identified the associations between perfluorooctane sulfonate (PFOS) or perfluorooctanoic acid (PFOA) exposure and epigenetic changes in both adult populations and birth cohorts. For in vitro studies, various cell types including neuroblasts, preadipocytes, and hepatocytes have been employed to understand epigenetic effects of PFAS. In studies with animal models, effects of early life exposure to PFAS have been examined using rodent models, and aquatic models (e.g., zebrafish) have been more frequently used in recent years. Several studies highlighted oxidative stress as a key mediator between epigenetic modification and health effects. Collectively, previous research clearly suggest involvement of epigenetic mechanisms in PFAS induced toxicity, though these efforts have primarily focused on specific PFASs (i.e. mainly PFOS and PFOA) or endpoints (i.e. cancer). Additional studies are necessary to define specific linkages among epigenetic mechanisms and related biomarkers or phenotypical changes. In addition, future research is also needed for understudied PFAS and complex mixtures. Studies of epigenetic effects elicited by individual PFAS and mixtures are needed within an adverse outcome pathways framework, which will advance an understanding of PFAS risks to public health and the environment, and support efforts to design less hazardous chemicals.
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•We critically reviewed epigenetic modifications elicited by PFAS.•Human epidemiological data, and in vitro, mammalian and aquatic studies were examined.•Evidence largely exists from studies with a few PFAS; thus, large data gaps exist.•Research is needed to examine linkages among mechanisms, biomarkers and outcomes.
Per- and polyfluoroalkyl substances (PFAS) can elicit epigenetic alterations, yet available evidence is limited to a few commonly studied compounds. Future environmental epigenetics efforts are needed for understudied PFAS, and to understand specific linkages among epigenetic mechanisms, related biomarkers and adverse outcomes.
•A decade has passed since we first published aquatic toxicology studies of fluoxetine.•Our report of the SSRIs fluoxetine and sertraline in fish was termed “Fish on Prozac”.•A mini-review presents ...scientific advances from studies to understand antidepressants.•A probabilistic assessment of fish therapeutic hazard to antidepressants is provided.•SSRIs and tricyclic antidepressants are predicted to present fish therapeutic hazards.
A decade has now passed since our research group initially reported several adverse effects of fluoxetine to aquatic organisms commonly employed for developing environmental quality criteria, evaluating whole effluent toxicity, and monitoring ambient toxicity of surface waters and sediments. Our subsequent observation of fluoxetine, sertraline and their active metabolites (norfluoxetine and desmethylsertraline, respectively) accumulating in muscle, liver and brain tissues of three different fish species from an effluent-dominated stream was termed “Fish on Prozac.” Here I briefly review some scientific lessons learned from our study of antidepressants and the environment, including opportunities for research, management, environmental education and public outreach. Intrinsic chemical properties of antidepressants and other pharmaceuticals have afforded research in areas ranging from analytical chemistry and comparative pharmacology, to influences of ionization, chirality and adverse outcome pathways on hazard and risk assessment, and further promises to support sustainable molecular design of less hazardous chemicals. Using probabilistic hazard assessment and fish plasma modeling approaches, selective serotonin reuptake inhibitors and tricyclic antidepressants are predicted to result in therapeutic hazard to fish (internal fish plasma level equaling mammalian therapeutic dose) when exposed to water (inhalational) at or below 1μg/L, a common trigger value for environmental assessments. Though many questions remain unanswered, studies of antidepressants in urbanizing aquatic systems have provided, and will continue to develop, an advanced understanding of environmental hazards and risks from pharmaceuticals and other contaminants.
As the global population becomes more concentrated in urban areas, resource consumption, including access to pharmaceuticals, is increasing and chemical use is also increasingly concentrated. ...Unfortunately, implementation of waste management systems and wastewater treatment infrastructure is not yet meeting these global megatrends. Herein, pharmaceuticals are indicators of an urbanizing water cycle; antidepressants are among the most commonly studied classes of these contaminants of emerging concern. In the present study, we performed a unique global hazard assessment of selective serotonin reuptake inhibitors (SSRIs) in water matrices across geographic regions and for common wastewater treatment technologies. SSRIs in the environment have primarily been reported from Europe (50%) followed by North America (38%) and Asia-Pacific (10%). Minimal to no monitoring data exists for many developing regions of the world, including Africa and South America. From probabilistic environmental exposure distributions, 5th and 95th percentiles for all SSRIs across all geographic regions were 2.31 and 3022.1 ng/L for influent, 5.3 and 841.6 ng/L for effluent, 0.8 and 127.7 ng/L for freshwater, and 0.5 and 22.3 ng/L for coastal and marine systems, respectively. To estimate the potential hazards of SSRIs in the aquatic environment, percent exceedances of therapeutic hazard values of specific SSRIs, without recommended safety factors, were identified within and among geographic regions. For influent sewage and wastewater effluents, sertraline exceedances were observed 49% and 29% of the time, respectively, demonstrating the need to better understand emerging water quality hazards of SSRIs in urban freshwater and coastal ecosystems. This unique global review and analysis identified regions where more monitoring is necessary, and compounds requiring toxicological attention, particularly with increasing aquatic reports of behavioral perturbations elicited by SSRIs.
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•Antidepressants are increasingly studied indicators of an urbanizing water cycle.•We reviewed and assessed global water quality hazards of SSRIs across matrices.•Therapeutic hazard exceedances were observed even without recommended safety factors.•We identify monitoring and research needs for specific SSRIs, matrices and regions.
Antibiotics in the environment usually co-exist with their transformation products with retained toxicity, raising concerns about environmental risks of their combined exposure. Herein, we reported a ...novel predictive approach for evaluating the individual and combined toxicity for photodegradation products of fluoroquinolone antibiotics (FQs). Quantitative structure-activity relationship (QSAR) models with promising predictive performance were constructed and validated using experimental data obtained with 13 FQs and 78 mixtures towards E. coli. A structural descriptor reflecting the interaction among FQ molecules and the target protein was employed in the QSAR models, which was obtained through molecular docking and thus provided a rational mechanistic explanation for these models. The predicted results indicated that the degradation products displayed varying degrees of changes compared to the parent FQs, while the combined toxicity of FQs and their degradation products was mostly additive. Furthermore, following UV irradiation the degradation products displayed elevated capacity of inducing resistance mutations in E. coli, though their overall toxicity was reduced. This result highlights the implications of antibiotic degradation products on resistance development in bacteria and stresses the importance of considering such impacts during environmental risk assessments of antibiotics.
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•Mixtures of fluoroquinolones (FQs) presented complex joint effects on bacteria.•FQs following UV treatment induced more resistance mutations in E. coli.•Interaction between FQ degradates and DNA gyrase was studied by molecular docking.•QSAR models were built for individual and mixture toxicity of FQ degradates.
Photodegradation products of fluoroquinolones showed retained toxicity that can be predicted by newly developed QSAR models and enhanced capacity of inducing resistance mutations in bacteria.
Environmental observations of antibiotics and other pharmaceuticals have received attention as indicators of an urbanizing global water cycle. When connections between environment and development of ...antibiotic resistance (ABR) are considered, it is increasingly important to understand the life cycle of antibiotics. Here we examined the global occurrence of erythromycin (ERY) in: 1. wastewater effluent, inland waters, drinking water, groundwater, and estuarine and coastal systems; 2. sewage sludge, biosolids and sediments; and 3. tissues of aquatic organisms. We then performed probabilistic environmental hazard assessments to identify probabilities of exceeding the predicted no-effect concentration (PNEC) of 1.0 μg L−1 for promoting ABR, based on previous modeling of minimum inhibitory concentrations and minimal selective concentrations of ERY, and measured levels from different geographic regions. Marked differences were observed among geographic regions and matrices. For example, more information was available for water matrices (312 publications) than solids (97 publications). ERY has primarily been studied in Asia, North America and Europe with the majority of studies performed in China, USA, Spain and the United Kingdom. In surface waters 72.4% of the Asian studies have been performed in China, while 85.4% of the observations from North America were from the USA; Spain represented 41.9% of the European surface water studies. Remarkably, results from PEHAs indicated that the likelihood of exceeding the ERY PNEC for ABR in effluents was markedly high in Asia (33.3%) followed by Europe (20%) and North America (17.8%). Unfortunately, ERY occurrence data is comparatively limited in coastal and marine systems across large geographic regions including Southwest Asia, Eastern Europe, Africa, and Central and South America. Future studies are needed to understand risks of ERY and other antibiotics to human health and the environment, particularly in developing regions where waste management systems and treatment infrastructure are being implemented slower than access to and consumption of pharmaceuticals is occurring.
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•Global antibiotic resistance (ABR) hazards of erythromycin (ERY) are poorly defined.•Critical review and probabilistic analyses were performed by matrix, global region.•Diverse geographic ABR exceedances were observed in effluents and surface waters.•ERY occurrence, ABR and life-cycle data is needed in rapidly developing countries.
Concentration of the global population is increasingly occurring in megacities and other developing regions, where access to medicines is increasing more rapidly than waste management systems are ...implemented. Because freshwater and coastal systems are influenced by wastewater effluent discharges of differential quality, exposures in aquatic systems must be considered. Here, we performed a global scanning assessment of antihistamines (AHs), a common class of medicines, in surface waters and effluents. Antihistamines were identified, literature occurrence and ecotoxicology data on AHs collated, therapeutic hazard values (THVs) calculated, and environmental exposure distributions (EEDs) of AHs compared to ecotoxicity thresholds and drug specific THVs to estimate hazards in surface waters and effluents. Literature searches of 62 different AHs in environmental matrices identified 111 unique occurrence publications of 24 specific AHs, largely from Asia-Pacific, Europe, and North America. However, the majority of surface water (63%) and effluent (85%) observations were from Europe and North America, which highlights relatively limited information from many regions, including developing countries and rapidly urbanizing areas in Africa, Latin America and Asia. Less than 10% of all observations were for estuarine or marine systems, though the majority of human populations reside close to coastal habitats. EED 5th and 95th centiles for all AHs were 2 and 212ng/L in surface water, 5 and 1308ng/L in effluent and 6 and 4287ng/L in influent, respectively. Unfortunately, global hazards and risks of AHs to non-target species remain poorly understood. However, loratadine observations in surface waters exceeded a THV without an uncertainty factor 40% of the time, indicating future research is needed to understand aquatic toxicology, hazards and risks associated with this AH. This unique global scanning study further illustrates the utility of global assessments of pharmaceuticals and other contaminants to identify chemicals requiring toxicology study and regions where environmental monitoring, assessment and management efforts appear limited and necessary.
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•Water quality hazards of antihistamines poorly understood within and among regions•Environmental occurrence data from megacities and developing continents is lacking•Cimetidine, diphenhydramine and ranitidine were commonly reported antihistamines•Limited ecotoxicology data and monitoring information for coastal and marine waters•Antihistamine therapeutic hazard thresholds exceeded in effluent and surface waters
Rapid urbanization represents a global megatrend that is resulting in an increasingly urban water cycle frequently contaminated by human medicines and other chemicals. Concentration of chemical ...consumption is occurring faster than implementation of environmental health systems and interventions, particularly in megacities of developing countries, while 80% of global sewage production remains untreated. In these urban areas, antibiotics in the environment influence development of antibiotic resistance (ABR) by pathogens. Here, we examined the occurrence of ciprofloxacin, designated a critically important antibiotic by the World Health Organization, in fresh surface water, groundwater, saltwater, treated municipal effluent, raw municipal sewage, treated hospital effluent, and raw hospital sewage around the world. We examined 260 articles reporting ciprofloxacin in these water matrices, including 111 studies from Europe, 105 from Asia, and 32 from North America. Only five and seven studies were identified from South America and Africa, respectively. Probabilistic hazard assessments were then performed to identify probabilities of exceedances of reported ABR and ecotoxicological predicted no effect concentrations (PNEC) for ciprofloxacin in water. Remarkably, across all geographic regions, 58% of municipal effluents exceeded the ABR PNEC (100ng/L) for ciprofloxacin, whereas ecotoxicity PNEC (1200ng/L) was exceeded 16% of the time. In surface water, 25% reported concentrations exceeded the ABR PNEC with 31% and 29% in Europe and North America, respectively, compared to 67% exceedance identified for Africa. Such observations highlight the importance of global scanning assessments to identify matrices and regions, including areas strategically advancing water reuse, for additional study and to prioritize locations for interventions aimed at reducing ABR development.
Commentary: Perspectives on aquaculture, urbanization and water quality Brooks, Bryan W.; Conkle, Jeremy L.
Comparative biochemistry and physiology. Part C, Toxicology & pharmacology/Comparative biochemistry and physiology. Toxicology & pharmacology,
March 2019, 2019-Mar, 2019-03-00, Letnik:
217
Journal Article
Recenzirano
Odprti dostop
Aquaculture presents essential opportunities to meet global food security needs, but adverse effects of aquaculture practices on ecological integrity and influences of existing waste management ...infrastructure on product safety must be understood in rapidly expanding urban and peri-urban regions. Concentration of, access to and use of chemical products is increasing in many urban areas faster than interventions are being implemented. Aquaculture farming is employing “non-traditional” (e.g., treated or untreated sewage) waters in some regions, but the spatial extent of these intentional or de facto water reuse practices with associated water quality and food safety systems are poorly understood around the world. Integrative water reuse, aquaculture product safety, ecological and public health research and advanced surveillance systems are needed. Such efforts appear particularly important because noncommunicable diseases are increasing and pollution is now recognized as one of the major global health threats, particularly in lower and middle income countries. Here we provide some modest perspectives and identify several research needs to support more sustainable aquaculture practices while protecting public health and the environment.
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Fish photolocomotor behavioral response (PBR) studies have become increasingly prevalent in pharmacological and toxicological research to assess the environmental impact of various chemicals. There ...is a need for a standard, reliable statistical method to analyze PBR data. The most common method currently used, univariate analysis of variance (ANOVA), does not account for temporal dependence in observations and leads to incomplete or unreliable conclusions. Repeated measures ANOVA, another commonly used method, has drawbacks in its interpretability for PBR study data. Because each observation is collected continuously over time, we instead consider each observation to be a function and apply functional ANOVA (FANOVA) to PBR data. Using the functional approach not only accounts for temporal dependency but also retains the full structure of the data and allows for straightforward interpretation in any subregion of the domain. Unlike the traditional univariate and repeated measures ANOVA, the FANOVA that we propose is nonparametric, requiring minimal assumptions. We demonstrate the disadvantages of univariate and repeated measures ANOVA using simulated data and show how they are overcome by applying FANOVA. We then apply one-way FANOVA to zebrafish data from a PBR study and discuss how those results can be reproduced for future PBR studies.
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