ABSTRACT
Growing evidence across organisms points to altered energy metabolism as an adverse outcome of metal oxide nanomaterial toxicity, with a mechanism of toxicity potentially related to the redox chemistry of processes involved in energy production. Despite this evidence, the significance of this mechanism has gone unrecognized in nanotoxicology due to the field's focus on oxidative stress as a universalâbut nonspecificânanotoxicity mechanism. To further explore metabolic impacts, we determined lithium cobalt oxide's (LCO's) effects on these pathways in the model organism Daphnia magna through global gene-expression analysis using RNA-Seq and untargeted metabolomics by direct-injection mass spectrometry. Our results show that a sublethal 1 mg/L 48 h exposure of D. magna to LCO nanosheets causes significant impacts on metabolic pathways versus untreated controls, while exposure to ions released over 48 h does not. Specifically, transcriptomic analysis using DAVID indicated significant enrichment (Benjamini-adjusted p ≤0.0.5) in LCO-exposed animals for changes in pathways involved in the cellular response to starvation (25 genes), mitochondrial function (70 genes), ATP-binding (70 genes), oxidative phosphorylation (53 genes), NADH dehydrogenase activity (12 genes), and protein biosynthesis (40 genes). Metabolomic analysis using MetaboAnalyst indicated significant enrichment (γ-adjusted p <0.1) for changes in amino acid metabolism (19 metabolites) and starch, sucrose, and galactose metabolism (7 metabolites). Overlap of significantly impacted pathways by RNA-Seq and metabolomics suggests amino acid breakdown and increased sugar import for energy production. Results indicate that LCO-exposed Daphnia respond to energy starvation by altering metabolic pathways, both at the gene expression and metabolite levels. These results support altered energy production as a sensitive nanotoxicity adverse outcome for LCO exposure and suggest negative impacts on energy metabolism as an important avenue for future studies of nanotoxicity, including for other biological systems and for metal oxide nanomaterials more broadly.
Subject(s)
Cobalt/pharmacology , Daphnia/drug effects , Nanostructures/chemistry , Oxides/pharmacology , Animals , Cobalt/chemistry , Daphnia/metabolism , Energy Metabolism , Oxides/chemical synthesis , Oxides/chemistryABSTRACT
The widespread nanomaterial use in commercial products has fed significant concern over environmental health and safety ramifications. Initially, little was known as to how these highly reactive particulates interacted with biological systems. Nanomaterials have introduced complexities not normally considered in traditional safety assessments of chemicals and therefore have generated uncertainty in the reliability of standard tests of safety. Advances in understanding the potential impacts of nanomaterials have occurred since their introduction, particularly for those used in the greatest quantities in commerce. The impact of characteristics such as charge, size, surface functionalization, chemical composition, and certain transformations on the potential effect of nanomaterials in the environment continue to move the field forward. However, generalizations of risk based on any one factor across nanomaterials is not possible. Estimating risk also remains difficult due to the introduction of materials that are new and more complex, minimal information on the specific molecular interactions of nanomaterials and organisms, and the need for more tools for measuring the dynamics of nanomaterial state and fate in complex matrices. Finally, exposure estimates are difficult due to difficulty of environmental monitoring which may be exacerbated by lack of information on nanomaterials in products and new uses in the marketplace.
Subject(s)
Commerce , Nanostructures , Commerce/standards , Environmental Monitoring/standards , Nanostructures/toxicity , Risk Assessment/trendsABSTRACT
Oxidative stress is frequently identified as a mechanism of toxicity of nanomaterials. However, rarely have the specific underlying molecular targets responsible for these impacts been identified. We previously demonstrated significant negative impacts of transition metal oxide (TMO) lithium-ion battery cathode nanomaterial, lithium cobalt oxide (LCO), on the growth, development, hemoglobin, and heme synthesis gene expression in the larvae of a model sediment invertebrate Chironomus riparius. Here, we propose that alteration of the Fe-S protein function by LCO is a molecular initiating event leading to these changes. A 10 mg/L LCO exposure causes significant oxidation of the aconitase 4Fe-4S center after 7 d as determined from the electron paramagnetic resonance spectroscopy measurements of intact larvae and a significant reduction in the aconitase activity of larval protein after 48 h (p < 0.05). Next-generation RNA sequencing identified significant changes in the expression of genes involved in 4Fe-4S center binding, Fe-S center synthesis, iron ion binding, and metabolism for 10 mg/L LCO at 48 h (FDR-adjusted, p < 0.1). We propose an adverse outcome pathway, where the oxidation of metabolic and regulatory Fe-S centers of proteins by LCO disrupts metabolic homeostasis, which negatively impacts the growth and development, a mechanism that may apply for these conserved proteins across species and for other TMO nanomaterials.
Subject(s)
Nanostructures , Oxides , Animals , Electric Power Supplies , Electron Spin Resonance Spectroscopy , Nanostructures/toxicity , Oxidation-Reduction , Oxides/toxicityABSTRACT
Effluent-dominated streams are becoming increasingly common in temperate regions and generate complex pharmaceutical mixture exposure conditions that may impact aquatic organisms via drug-drug interactions. Here, we quantified spatiotemporal pharmaceutical exposure concentrations and composition mixture dynamics during baseflow conditions at four sites in a temperate-region effluent-dominated stream (upstream, at, and progressively downstream from effluent discharge). Samples were analyzed monthly for 1 year for 109 pharmaceuticals/degradates using a comprehensive U.S. Geological Survey analytical method and biweekly for 2 years focused on 14 most common pharmaceuticals/degradates. We observed a strong chemical gradient with pharmaceuticals only sporadically detected upstream from the effluent. Seventy-four individual pharmaceuticals/degradates were detected, spanning 5 orders of magnitude from 0.28 to 13â¯500 ng/L, with 38 compounds detected in >50% of samples. "Biweekly" compounds represented 77 ± 8% of the overall pharmaceutical concentration. The antidiabetic drug metformin consistently had the highest concentration with limited in-stream attenuation. The antihistamine drug fexofenadine inputs were greater during warm- than cool-season conditions but also attenuated faster. Differential attenuation of individual pharmaceuticals (i.e., high = citalopram; low = metformin) contributed to complex mixture evolution along the stream reach. This research demonstrates that variable inputs over multiple years and differential in-stream attenuation of individual compounds generate evolving complex mixture exposure conditions for biota, with implications for interactive effects.
Subject(s)
Pharmaceutical Preparations , Water Pollutants, Chemical , Aquatic Organisms , Environmental Monitoring , Waste Disposal, Fluid , Wastewater , Water Pollutants, Chemical/analysisABSTRACT
Most studies of nanomaterial environmental impacts have focused on relatively simple first-generation nanomaterials, including metals or metal oxides (e.g., Ag, ZnO) for which dissolution largely accounts for toxicity. Few studies have considered nanomaterials with more complex compositions, such as complex metal oxides, which represent an emerging class of next-generation nanomaterials used in commercial products at large scales. Importantly, many nanomaterials are not colloidally stable in aqueous environments and will aggregate and settle, yet most studies use pelagic rather than benthic-dwelling organisms. Here we show that exposure of the model benthic species Chironomus riparius to lithium cobalt oxide (Li xCo1- xO2, LCO) and lithium nickel manganese cobalt oxide (Li xNi yMn zCo1- y- zO2, NMC) at 10 and 100 mg·L-1 caused 30-60% declines in larval growth and a delay of 7-25 d in adult emergence. A correlated 41-48% decline in larval hemoglobin concentration and related gene expression changes suggest a potential adverse outcome pathway. Metal ions released from nanoparticles do not cause equivalent impacts, indicating a nanospecific effect. Nanomaterials settled within 2 days and indicate higher cumulative exposures to sediment organisms than those in the water column, making this a potentially realistic environmental exposure. Differences in toxicity between NMC and LCO indicate compositional tuning may reduce material impact.
Subject(s)
Chironomidae , Nanostructures , Water Pollutants, Chemical , Animals , Geologic Sediments , Invertebrates , Metals , OxidesABSTRACT
Nanodiamonds are a type of engineered nanomaterial with high surface area that is highly tunable and are being proposed for use as a material for medical imaging or drug delivery to composites. With their potential for widespread use they may potentially be released into the aquatic environment as are many chemicals used for these purposes. It is generally thought that nanodiamonds are innocuous, but toxicity may occur due to surface functionalization. This study investigated the potential oxidative stress and antioxidant response of enterocytes in a freshwater invertebrate, Daphnia magna, a common aquatic invertebrate for ecotoxicological studies, in response to two types of functionalized nanodiamonds (polyallylamine and oxidized). We also examined how the size of the nanomaterial may influence toxicity by testing two different sizes (5â¯nm and 15â¯nm) of nanodiamonds with the same functionalization. Adults of Daphnia magna were exposed to three concentrations of each of the nanodiamonds for 24â¯h. We found that both 5 and 15â¯nm polyallylamine nanodiamond and oxidized nanodiamond induced the production of reactive oxygen species in tissues. The smaller 5â¯nm nanodiamond induced a significant change in the expression of heat shock protein 70 and glutathione-S-transferase. This may suggest that daphnids mounted an antioxidant response to the oxidative effects of 5â¯nm nanodiamonds but not the comparative 15â¯nm nanodiamonds with either surface chemistry. Outcomes of this study reveal that functionalized nanodiamond may cause oxidative stress and may potentially initiate lipid peroxidation of enterocyte cell membranes in freshwater organisms, but the impact of the exposure depends on the particle size.
Subject(s)
Daphnia/drug effects , Nanodiamonds , Oxidative Stress , Animals , Antioxidants/metabolism , Lipid Peroxidation , Reactive Oxygen Species/metabolismABSTRACT
There are currently over ninety products incorporating carbon nanomaterials (CNMs) on the market today for a variety of applications. Modifications in core structure and surface chemistry of manufactured nanomaterials are used to optimize nanomaterials for specific uses. However, there is a notable lack of information on how core structure and surface chemistry may alter toxicity in low-level, chronic exposures. This paper examines the effects of twelve CNMs that differ in their core structure and surface chemistry to Daphnia magna over a 21-day chronic exposure. Overall, nanomaterials with a carbon nanotube core were more toxic to daphnids than fullerenes, with the one exception of fullerenes with a gamma-cyclodextrin surface chemistry. Acute mortality was not a good predictor of chronic effects as none of the CNMs induced toxicity at tested concentrations after 48 h, yet chronic assays indicated significant differences in mortality, reproduction, and growth realized after 21 days. Our results indicate that (1) acute exposure assays do not accurately describe the impact of CNMs to biological systems, (2) chronic exposures provide valuable information that indicates the potential for different modes of action for nanomaterials of differing chemistries, and (3) core structure and surface chemistry both influence particle toxicity.
Subject(s)
Daphnia/drug effects , Nanotubes, Carbon/toxicity , Animals , Body Size/drug effects , Reproduction/drug effects , Toxicity Tests, Acute , Toxicity Tests, ChronicABSTRACT
Wastewater treatment plant (WWTP) effluent-dominated streams provide critical habitat for aquatic and terrestrial organisms but also continually expose them to complex mixtures of pharmaceuticals that can potentially impair growth, behavior, and reproduction. Currently, few biomarkers are available that relate to pharmaceutical-specific mechanisms of action. In the experiment reported in this paper, zebrafish (Danio rerio) embryos at two developmental stages were exposed to water samples from three sampling sites (0.1 km upstream of the outfall, at the effluent outfall, and 0.1 km below the outfall) during base-flow conditions from two months (January and May) of a temperate-region effluent-dominated stream containing a complex mixture of pharmaceuticals and other contaminants of emerging concern. RNA-sequencing identified potential biological impacts and biomarkers of WWTP effluent exposure that extend past traditional markers of endocrine disruption. Transcriptomics revealed changes to a wide range of biological functions and pathways including cardiac, neurological, visual, metabolic, and signaling pathways. These transcriptomic changes varied by developmental stage and displayed sensitivity to variable chemical composition and concentration of effluent, thus indicating a need for stage-specific biomarkers. Some transcripts are known to be associated with genes related to pharmaceuticals that were present in the collected samples. Although traditional biomarkers of endocrine disruption were not enriched in either month, a high estrogenicity signal was detected upstream in May and implicates the presence of unidentified chemical inputs not captured by the targeted chemical analysis. This work reveals associations between bioeffects of exposure, stage of development, and the composition of chemical mixtures in effluent-dominated surface water. The work underscores the importance of measuring effects beyond the endocrine system when assessing the impact of bioactive chemicals in WWTP effluent and identifies a need for non-targeted chemical analysis when bioeffects are not explained by the targeted analysis.
Subject(s)
Wastewater , Water Pollutants, Chemical , Animals , Wastewater/chemistry , Rivers/chemistry , Zebrafish/metabolism , Transcriptome , Waste Disposal, Fluid , Larva/metabolism , Water Pollutants, Chemical/analysis , Seasons , Water/analysis , Pharmaceutical PreparationsABSTRACT
Wastewater effluent-dominated streams are becoming increasingly common worldwide, including in temperate regions, with potential impacts on ecological systems and drinking water sources. We recently quantified the occurrence/ spatiotemporal dynamics of pharmaceutical mixtures in a representative temperate-region wastewater effluent-dominated stream (Muddy Creek, Iowa) under baseflow conditions and characterized relevant fate processes. Herein, we quantified the ecological risk quotients (RQs) of 19 effluent-derived contaminants of emerging concern (CECs; including: 14 pharmaceuticals, 2 industrial chemicals, and 3 neonicotinoid insecticides) and 1 run-off-derived compound (atrazine) in the stream under baseflow conditions, and estimated the probabilistic risks of effluent-derived CECs under all-flow conditions (i.e., including runoff events) using stochastic risk modeling. We determined that 11 out of 20 CECs pose medium-to-high risks to local ecological systems (i.e., algae, invertebrates, fish) based on literature-derived acute effects under measured baseflow conditions. Stochastic risk modeling indicated decreased, but still problematic, risk of effluent-derived CECs (i.e., RQ≥0.1) under all-flow conditions when runoff events were included. Dilution of effluent-derived chemicals from storm flows thus only minimally decreased risk to aquatic biota in the effluent-dominated stream. We also modeled in-stream transport. Thirteen out of 14 pharmaceuticals persisted along the stream reach (median attenuation rate constant k<0.1 h-1) and entered the Iowa River at elevated concentrations. Predicted and measured concentrations in the drinking water treatment plant were below the human health benchmarks. This study demonstrates the application of probabilistic risk assessments for effluent-derived CECs in a representative effluent-dominated stream under variable flow conditions (when measurements are less practical) and provides an enhanced prediction tool transferable to other effluent-dominated systems.
ABSTRACT
The fluorescence intensity emitted by nitrogen-vacancy (NV) centers in diamond nanoparticles can be readily modulated by the application of a magnetic field using a small electromagnet. By acquiring interleaved images acquired in the presence and absence of the magnetic field and performing digital subtraction, the fluorescence intensity of the NV nanodiamond can be isolated from scattering and autofluorescence even when these backgrounds are changing monotonically during the experiments. This approach has the potential to enable the robust identification of nanodiamonds in organisms and other complex environments. Yet, the practical application of magnetic modulation imaging to realistic systems requires the use of quantitative analysis methods based on signal-to-noise considerations. Here, we describe the use of magnetic modulation to analyze the uptake of diamond nanoparticles from an aqueous environment into Caenorhabditis elegans, used here as a model system for identification and quantification of nanodiamonds in complex matrices. Based on the observed signal-to-noise ratio of sets of digitally subtracted images, we show that nanodiamonds can be identified on an individual pixel basis with a >99.95% confidence. To determine whether surface functionalization of the nanodiamond significantly impacted uptake, we used this approach to analyze the presence of nanodiamonds in C. elegans that had been exposed to these functionalized nanodiamonds in the water column, with uptake likely occurring by ingestion. In each case, the images show a significant nanoparticle uptake. However, differences in uptake between the three ligands were not outside of the experimental error, indicating that additional factors beyond the surface charge are important factors controlling uptake. Analysis of the number of pixels above the threshold in individual C. elegans organisms revealed distributions that deviate significantly from a Poisson distribution, suggesting that uptake of nanoparticles may not be a statistically independent event. The results presented here demonstrate that magnetic modulation combined with quantitative analysis of the resulting images can be used to robustly characterize nanoparticle uptake into organisms.
ABSTRACT
Discharged wastewater treatment plant (WWTP) effluent greatly contributes to the generation of complex mixtures of contaminants of emerging concern (CECs) in aquatic environments which often contain neuropharmaceuticals and other emerging contaminants that may impact neurological function. However, there is a paucity of knowledge on the neurological impacts of these exposures to aquatic organisms. In this study, caged fathead minnows (Pimephales promelas) were exposed in situ in a temperate-region effluent-dominated stream (i.e., Muddy Creek) in Coralville, Iowa, USA upstream and downstream of a WWTP effluent outfall. The pharmaceutical composition of Muddy Creek was recently characterized by our team and revealed many compounds there were at a low microgram to high nanogram per liter concentration. Total RNA sequencing analysis on brain tissues revealed 280 gene isoforms that were significantly differentially expressed in male fish and 293 gene isoforms in female fish between the upstream and downstream site. Only 66 (13%) of such gene isoforms overlapped amongst male and female fish, demonstrating sex-dependent impacts on neuronal gene expression. By using a systems biology approach paired with functional enrichment analyses, we identified several potential novel gene biomarkers for treated effluent exposure that could be used to expand monitoring of environmental effects with respect to complex CEC mixtures. Lastly, when comparing the results of this study to those that relied on a single-compound approach, there was relatively little overlap in terms of gene-specific effects. This discovery brings into question the application of single-compound exposures in accurately characterizing environmental risks of complex mixtures and for gene biomarker identification.
Subject(s)
Cyprinidae , Water Pollutants, Chemical , Animals , Wastewater/toxicity , Wastewater/analysis , RNA-Seq , Water Pollutants, Chemical/analysis , Cyprinidae/genetics , Cyprinidae/metabolism , Biomarkers/metabolism , Pharmaceutical PreparationsABSTRACT
Physico-chemical characteristics of engineered nanomaterials are known to be important in determining the impact on organisms but effects are equally dependent upon the characteristics of the organism exposed. Species sensitivity may vary by orders of magnitude, which could be due to differences in the type or magnitude of the biochemical response, exposure or uptake of nanomaterials. Synthesizing conclusions across studies and species is difficult as multiple species are not often included in a study, and differences in batches of nanomaterials, the exposure duration and media across experiments confound comparisons. Here three model species, Danio rerio, Daphnia magna and Chironomus riparius, that differ in sensitivity to lithium cobalt oxide nanosheets are found to differ in immune-response, iron-sulfur protein and central nervous system pathways, among others. Nanomaterial uptake and dissolution does not fully explain cross-species differences. This comparison provides insight into how biomolecular responses across species relate to the varying sensitivity to nanomaterials.
Subject(s)
Nanostructures , Water Pollutants, Chemical , Animals , Daphnia/metabolism , Transcriptome , Water Pollutants, Chemical/metabolism , Water Pollutants, Chemical/pharmacologyABSTRACT
BACKGROUND: Methods for gene-class testing, such as Gene Set Enrichment Analysis (GSEA), incorporate biological knowledge into the analysis and interpretation of microarray data by comparing gene expression patterns to pathways, systems and emergent phenotypes. However, to use GSEA to its full capability with non-mammalian model organisms, a microarray platform must be annotated with human gene symbols. Doing so enables the ability to relate a model organism's gene expression, in response to a given treatment, to potential human health consequences of that treatment. We enhanced the annotation of a microarray platform from a non-mammalian model organism, and then used the GSEA approach in a reanalysis of a study examining the biological significance of acute and chronic methylmercury exposure on liver tissue of fathead minnow (Pimephales promelas). Using GSEA, we tested the hypothesis that fathead livers, in response to methylmercury exposure, would exhibit gene expression patterns similar to diseased human livers. RESULTS: We describe an enhanced annotation of the fathead minnow microarray platform with human gene symbols. This resource is now compatible with the GSEA approach for gene-class testing. We confirmed that GSEA, using this enhanced microarray platform, is able to recover results consistent with a previous analysis of fathead minnow exposure to methylmercury using standard analytical approaches. Using GSEA to compare fathead gene expression profiles to human phenotypes, we also found that fathead methylmercury-treated livers exhibited expression profiles that are homologous to human systems & pathways and results in damage that is similar to those of human liver damage associated with hepatocellular carcinoma and hepatitis B. CONCLUSIONS: This study describes a powerful resource for enabling the use of non-mammalian model organisms in the study of human health significance. Results of microarray gene expression studies involving fathead minnow, typically used for aquatic ecological toxicology studies, can now be used to generate hypotheses regarding consequences of contaminants and other stressors on humans. The same approach can be used with other model organisms with microarray platforms annotated in a similar manner.
Subject(s)
Cyprinidae/genetics , Oligonucleotide Array Sequence Analysis/methods , Animals , Molecular Sequence AnnotationABSTRACT
Neonicotinoids in aquatic systems have been predominantly associated with agriculture, but some are increasingly being linked to municipal wastewater. Thus, the aim of this work was to understand the municipal wastewater contribution to neonicotinoids in a representative, characterized effluent-dominated temperate-region stream. Our approach was to quantify the spatiotemporal concentrations of imidacloprid, clothianidin, thiamethoxam, and transformation product imidacloprid urea: 0.1 km upstream, the municipal wastewater effluent, and 0.1 and 5.1 km downstream from the wastewater outfall (collected twice-monthly for one year under baseflow conditions). Quantified results demonstrated that wastewater effluent was a point-source of imidacloprid (consistently) and clothianidin (episodically), where chronic invertebrate exposure benchmarks were exceeded for imidacloprid (36/52 samples; 3/52 > acute exposure benchmark) and clothianidin (8/52 samples). Neonicotinoids persisted downstream where mass loads were not significantly different than those in the effluent. The combined analysis of neonicotinoid effluent concentrations, instream seasonality, and registered uses in Iowa all indicate imidacloprid, and seasonally clothianidin, were driven by wastewater effluent, whereas thiamethoxam and imidacloprid urea were primarily from upstream non-point sources (or potential in-stream transformation for imidacloprid urea). This is the first study to quantify neonicotinoid persistence in an effluent-dominated stream throughout the year-implicating wastewater effluent as a point-source for imidacloprid (year-round) and clothianidin (seasonal). These findings suggest possible overlooked neonicotinoid indoor human exposure routes with subsequent implications for instream ecotoxicological exposure.
Subject(s)
Insecticides , Animals , Guanidines , Humans , Insecticides/analysis , Invertebrates , Neonicotinoids , Thiamethoxam , WastewaterABSTRACT
Evolving complex mixtures of pharmaceuticals and transformation products in effluent-dominated streams pose potential impacts to aquatic species; thus, understanding the attenuation dynamics in the field and characterizing the prominent attenuation mechanisms of pharmaceuticals and their transformation products (TPs) is critical for hazard assessments. Herein, we determined the attenuation dynamics and the associated prominent mechanisms of pharmaceuticals and their corresponding TPs via a combined long-term field study and controlled laboratory experiments. For the field study, we quantified spatiotemporal exposure concentrations of five pharmaceuticals and six associated TPs in a small, temperate-region effluent-dominated stream during baseflow conditions where the wastewater plant was the main source of pharmaceuticals. We selected four sites (upstream, at, and two progressively downstream from effluent discharge) and collected water samples at 16 time points (64 samples in total, approximately twice monthly, depending on flows) for 1 year. Concurrently, we conducted photolysis, sorption, and biodegradation batch tests under controlled conditions to determine the major attenuation mechanisms. We observed 10-fold greater attenuation rates in the field compared to batch tests, demonstrating that connecting laboratory batch tests with field measurements to enhance predictive power is a critical need. Batch systems alone, often used for assessment, are useful for determining fate processes but poorly approximate in-stream attenuation kinetics. Sorption was the dominant attenuation process (t1/2<7.7 d) for 5 of 11 compounds in the batch tests, while the other compounds (n = 6) persisted in the batch tests and along the 5.1 km stream reach. In-stream parent-to-product transformation was minimal. Differential attenuation contributed to the evolving pharmaceutical mixture and created changing exposure conditions with concomitant implications for aquatic and terrestrial biota. Tandem field and laboratory characterization can better inform modeling efforts for transport and risk assessments.
Subject(s)
Pharmaceutical Preparations , Water Pollutants, Chemical , Environmental Monitoring , Laboratories , Wastewater/analysis , Water Pollutants, Chemical/analysisABSTRACT
Surface properties of engineered nanomaterials (ENMs) have been shown to influence their interaction with biological systems. However, studies to date have largely focused on hydrophilic materials, likely due to biocompatibility concerns and aqueous exposure conditions necessary for many model systems. Therefore, a knowledge gap exists in nanotoxicity literature for impacts of hydrophobic ENMs, with studies of hydrophobic materials largely limited to carbon ENMs. Here we demonstrate testing of hydrophobic quantum dots (QDs) using the nematode C. elegans, a model soil organism cultured on solid media and amenable to hydrophobic exposures. To evaluate the influence of hydrophobicity, we compared CdSe/ZnS QDs functionalized with hydrophobic trioctylphosphine oxide (TOPO) to identical QDs functionalized with hydrophilic dihydrolipoic acid-polyethylene glycol (DHLA-PEG) and alternative hydrophobic CdSe/ZnS QDs functionalized with oleic acid (OA). Results show that hydrophobic TOPO QDs are significantly more toxic than hydrophilic DHLA-PEG QDs, and substitution of TOPO with OA yields relatively non-toxic hydrophobic QDs. Fluorescence microscopy shows TOPO QDs loosely associated with the organism's cuticle, but atomic force microscopy shows no difference in cuticle structure from exposure. Importantly, TOPO ligand alone is as toxic as TOPO QDs, and our data suggests that TOPO may impact neuromuscular function, perhaps upon displacement from the QD surface. This study demonstrates the importance of examining ligand-specific impacts of hydrophobic ENMs and indicates OA-functionalized QDs as a potential alternative to TOPO QDs for reduced toxicity.
Subject(s)
Quantum Dots , Animals , Caenorhabditis elegans , Hydrophobic and Hydrophilic Interactions , Ligands , Quantum Dots/toxicity , Surface PropertiesABSTRACT
Anticipating, identifying, and prioritizing strategic needs represent essential activities by research organizations. Decided benefits emerge when these pursuits engage globally important environment and health goals, including the United Nations Sustainable Development Goals. To this end, horizon scanning efforts can facilitate identification of specific research needs to address grand challenges. We report and discuss 40 priority research questions following engagement of scientists and engineers in North America. These timely questions identify the importance of stimulating innovation and developing new methods, tools, and concepts in environmental chemistry and toxicology to improve assessment and management of chemical contaminants and other diverse environmental stressors. Grand challenges to achieving sustainable management of the environment are becoming increasingly complex and structured by global megatrends, which collectively challenge existing sustainable environmental quality efforts. Transdisciplinary, systems-based approaches will be required to define and avoid adverse biological effects across temporal and spatial gradients. Similarly, coordinated research activities among organizations within and among countries are necessary to address the priority research needs reported here. Acquiring answers to these 40 research questions will not be trivial, but doing so promises to advance sustainable environmental quality in the 21st century. Environ Toxicol Chem 2019;38:1606-1624. © 2019 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.
Subject(s)
Conservation of Natural Resources , Ecotoxicology , Research , Conservation of Natural Resources/economics , Conservation of Natural Resources/methods , Conservation of Natural Resources/trends , Humans , North America , Sustainable DevelopmentABSTRACT
The presence of intersex fish in watersheds around the world is a warning of the presence of anthropogenic endocrine-disrupting compounds (EDCs) being deposited into the aquatic environment. The anti-diabetic drug metformin is among the most prevalent and ubiquitous of the myriad pharmaceuticals found in wastewater effluent and watersheds worldwide. In addition to its prescription for type-2 diabetes, metformin is indicated as a treatment in cancers and the endocrine disorder polycystic ovarian syndrome (PCOS). Our previous research found evidence of endocrine-disruption following Pimephales promelas (fathead minnow) exposure to metformin at an environmentally relevant concentration. However, the mechanism of action leading to these impacts is unknown. Although metformin does not structurally resemble classical EDCs, there's an increasing recognition that endocrine disruption may occur by mechanisms other than classical endocrine receptor binding, and metformin's off-label use for treating endocrine-related disorders such as PCOS indicates its potential interaction with the endocrine system. To further explore metformin's mechanism of action as an EDC, we measured expression of numerous endocrine-related genes in male fathead minnows exposed to metformin at a low-dose similar to that found in wastewater effluent and the environment (40⯵gâ¯L-1) for a full year (early development to adulthood) and discovered significant upregulation of the AR (3.6⯱â¯0.9-fold), 3ß-HSD (3.9⯱â¯0.8-fold), 17ß-HSD (17⯱â¯4-fold), CYP19A1 (40⯱â¯20-fold), and SULT2A1 (2.3⯱â¯0.4-fold) genes in exposed male gonad. We also found a significant correlation between expression of 3ß-HSD, 17ß-HSD, and CYP19A1 in testis of metformin-treated male fish and the degree of intersex occurring in their gonads. These results provide additional evidence of the endocrine disrupting impact of the drug metformin and insight into the potential mechanisms by which metformin may influence the endocrine system in aquatic organisms.
Subject(s)
Cyprinidae/genetics , Endocrine Disruptors/metabolism , Gene Expression Regulation , Metformin/adverse effects , Animals , Cyprinidae/blood , Disorders of Sex Development , Female , Gene Expression Regulation/drug effects , Male , Testis/drug effects , Testis/metabolism , Testosterone/blood , Vitellogenins/blood , Water Pollutants, Chemical/toxicityABSTRACT
Toxicity of nanomaterials to ecological systems has recently emerged as an important field of research, and thus, many researchers are exploring the mechanisms of how nanoparticles impact organisms. Herein, we probe the mechanisms of bacteria-nanoparticle interaction by investigating how TiO2 nanoparticles impact a model organism, the metal-reducing bacterium Shewanella oneidensis MR-1. In addition to examining the effect of TiO2 exposure, the effect of synergistic simulated solar irradiation containing UV was explored in this study, as TiO2 nanoparticles are known photocatalysts. The data reveal that TiO2 nanoparticles cause an inhibition of S. oneidensis growth at high dosage without compromising cell viability, yet co-exposure of nanoparticles and illumination does not increase the adverse effects on bacterial growth relative to TiO2 alone. Measurements of intracellular reactive oxygen species and riboflavin secretion, on the same nanoparticle-exposed bacteria, reveal that TiO2 nanoparticles have no effect on these cell functions, but application of UV-containing illumination with TiO2 nanoparticles has an impact on the level of riboflavin outside bacterial cells. Finally, gene expression studies were employed to explore how cells respond to TiO2 nanoparticles and illumination, and these results were correlated with cell growth and cell function assessment. Together these data suggest a minimal impact of TiO2 NPs and simulated solar irradiation containing UV on S. oneidensis MR-1, and the minimal impact could be accounted for by the nutrient-rich medium used in this work. These measurements demonstrate a comprehensive scheme combining various analytical tools to enable a mechanistic understanding of nanoparticle-cell interactions and to evaluate the potential adverse effects of nanoparticles beyond viability/growth considerations.