Assessing the Toxicity of Benzotriazole Ultraviolet Stabilizers to Fishes: Insights into Aryl Hydrocarbon Receptor-Mediated Effects.

Benzotriazole ultraviolet stabilizers (BUVSs) are chemicals used to mitigate UV-induced damage to manufactured goods. Their presence in aquatic environments and biota raises concerns, as certain BUVSs activate the aryl hydrocarbon receptor (AhR), which is linked to adverse effects in fish. However, potencies of BUVSs as AhR agonists and species sensitivities to AhR activation are poorly understood. This study evaluated the toxicity of three BUVSs using embryotoxicity assays. Zebrafish (Danio rerio) embryos exposed to BUVSs by microinjection suffered dose-dependent increases in mortality, with LD50 values of 4772, 11 608, and 56 292 ng/g-egg for UV-P, UV-9, and UV-090, respectively. The potencies and species sensitivities to AhR2 activation by BUVSs were assessed using a luciferase reporter gene assay with COS-7 cells transfected with the AhR2 of zebrafish and eight other fishes. The rank order of potency for activation of the AhR2 from all nine species was UV-P > UV-9 > UV-090. However, AhR2s among species differed in sensitivities to activation by up to 100-fold. An approximate reversed rank order of species sensitivity was observed compared to the rank order of sensitivity to 2,3,7,8-tetrachlorodibenzo[p]dioxin, the prototypical AhR agonist. Despite this, a pre-existing quantitative adverse outcome pathway linking AhR activation to embryo lethality could predict embryotoxicities of BUVSs in zebrafish.

Daphnia magna digestive activity is differentially altered when exposed to equally turbid waters caused by either suspended sediment or suspended microplastics.

Turbidity can be a result of suspended natural particles, such as sediment, or anthropogenic particles such as microplastics. This study assessed whether Daphnia magna, a pelagic filter feeder known to ingest suspended particles, have an altered response to equally turbid environments caused by the presence of either suspended bentonite or suspended polyethylene microplastics. Compared to controls, daphnids exposed to suspended bentonite maintained their feeding efficiency and increased their digestive activity, as measured by mandibular movement, peristalsis, and expulsion, to pass bentonite through the digestive tract. The same effects were not seen in microplastic-exposed individuals, in which feeding efficiency was decreased and only peristaltic movement was increased but without a coordinated increase in expulsion, suggesting that microplastics do not have the same ability as bentonite to pass through the digestive tract. This study highlights the need to discern the identities of particulates contributing to turbid environments as different particles, even of the same size, can have different effects on filter feeders, which inherently ingest suspended particles.

Interspecies Differences in 6PPD-Quinone Toxicity Across Seven Fish Species: Metabolite Identification and Semiquantification.

N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-Q) is a recently identified contaminant that originates from the oxidation of the tire antidegradant 6PPD. 6PPD-Q is acutely toxic to select salmonids at environmentally relevant concentrations, while other fish species display tolerance to concentrations that surpass those measured in the environment. The reasons for these marked differences in sensitivity are presently unknown. The objective of this research was to explore potential toxicokinetic drivers of species sensitivity by characterizing biliary metabolites of 6PPD-Q in sensitive and tolerant fishes. For the first time, we identified an O-glucuronide metabolite of 6PPD-Q using high-resolution mass spectrometry. The semiquantified levels of this metabolite in tolerant species or life stages, including white sturgeon (Acipenser transmontanus), chinook salmon (Oncorhynchus tshawytscha), westslope cutthroat trout (Oncorhynchus clarkii lewisi), and nonfry life stages of Atlantic salmon (Salmo salar), were greater than those in sensitive species, including coho salmon (Oncorhynchus kisutch), brook trout (Salvelinus fontinalis), and rainbow trout (Oncorhynchus mykiss), suggesting that tolerant species might detoxify 6PPD-Q more effectively. Thus, we hypothesize that differences in species sensitivity are a result of differences in basal expression of biotransformation enzyme across various fish species. Moreover, the semiquantification of 6PPD-Q metabolites in bile extracted from wild-caught fish might be a useful biomarker of exposure to 6PPD-Q, thereby being valuable to environmental monitoring and risk assessment.

The Combined Effect of Copper Nanoparticles and Microplastics on Transcripts Involved in Oxidative Stress Pathway in Rainbow Trout (Oncorhynchus Mykiss) Hepatocytes.

Copper nanoparticles (CuNPs) and microplastics (MPs) are two emerging contaminants of freshwater systems. Despite their co-occurrence in many water bodies, the combined effects of CuNPs and MPs on aquatic organisms are not well-investigated. In this study, primary cultures of rainbow trout hepatocytes were exposed to dissolved Cu, CuNPs, MPs, or a combination of MPs and CuNPs for 48 h, and the transcript abundances of oxidative stress-related genes were investigated. Exposure to CuNPs or dissolved Cu resulted in a significant increase in the transcript abundances of two antioxidant enzymes, catalase (CAT) and superoxide dismutase (SOD). Exposure to CuNPs also led to an upregulation in the expression of Na+/K+ ATPase alpha 1 subunit (ATP1A1). Microplastics alone or in combination with CuNPs did not have a significant effect on abundances of the target gene transcripts. Overall, our findings suggested acute exposure to CuNPs or dissolved ions may induce oxidative stress in hepatocytes, and the Cu-induced effect on target gene transcripts was not associated with MPs.

Toxicity of Weathered Sediment-Bound Dilbit to Early Life Stages of Zebrafish (Danio rerio).

Due to high viscosity, bitumen extracted from the Alberta oil sands is diluted with natural gas condensates to form diluted bitumen (dilbit) to facilitate transport through pipelines. Dilbit that is spilled into or near a waterbody is subject to environmental weathering processes such as evaporation and interaction with sediments. This is the first study that assessed the toxicity of weathered sediment-bound dilbit (WSD) to fish early life stages. Exposure of zebrafish (Danio rerio) embryos to water-soluble fractions (WSFs) or water-accommodated fractions (WAFs) of WSD from 30 min to 120 h postfertilization resulted in pericardial edema, yolk sac edema, and incidences of uninflated swim bladder. The presence of oil-mineral aggregates (OMAs) in the WAFs greatly increased toxicity, despite all fractions having similar concentrations of dissolved polycyclic aromatic hydrocarbons (PAHs). There were greater cyp1a mRNA abundances in larvae exposed to WAFs, suggesting that there were differences in bioavailability of PAHs between fractions. However, there was little evidence that embryotoxicity was caused by oxidative stress. Results suggest that evaporation and sediment interaction do not completely attenuate toxicity of dilbit to zebrafish early life stages, and OMAs in exposures exacerbate toxicity.

Identification of molecular toxicity pathways across early life-stages of zebrafish exposed to PCB126 using a whole transcriptomics approach.

Although withdrawn from the market in the 1980s, polychlorinated biphenyls (PCBs) are still found ubiquitously in the aquatic environment and pose a serious risk to biota due to their teratogenic potential. In fish, early life-stages are often considered most sensitive with regard to their exposure to PCBs and other dioxin-like compounds. However, little is known about the molecular drivers of the frequently observed teratogenic effects. Therefore, the aims of our study were to: (1) characterize the baseline transcriptome profiles at different embryonic life-stages in zebrafish (Danio rerio); and (2) to identify the molecular response to PCB exposure and life-stage specific-effects of the chemical on associated processes. For both objectives, embryos were sampled at 12, 48, and 96 h post-fertilization (hpf) and subjected to Illumina sequence-by-synthesis and RNAseq analysis. Results revealed that with increasing age more genes and related pathways were upregulated both in terms of number and magnitude. Yet, other transcripts followed an opposite pattern with greater transcript abundance at the earlier time points. Additionally, embryos were exposed to PCB126, a potent agonist of the aryl hydrocarbon receptor (AHR). ClueGO network analysis revealed significant enrichment of genes associated with basic cell metabolism, communication, and homeostasis as well as eye development, muscle formation, and skeletal formation. We selected eight genes involved in the affected pathways for an in-depth characterization of their regulation throughout normal embryogenesis and after exposure to PCB126 by quantification of transcript abundances every 12 h until 118 hpf. Among these, fgf7 and c9 stood out because of their strong upregulation by PCB126 exposure at 48 and 96 hpf, respectively. Cyp2aa12 was upregulated from 84 hpf on. Fabp10ab, myhz1.1, col8a1a, sulf1, and opn1sw1 displayed specific regulation depending on the developmental stage. Overall, we demonstrate that (1) the developmental transcriptome of zebrafish is highly dynamic, and (2) dysregulation of gene expression by exposure to PCB126 was significant and in several cases not directly connected to AHR-signaling. Hence, this study improves the understanding of linkages between molecular events and apical outcomes that are of regulatory relevance.

Mechanisms of pH-Dependent Uptake of Ionizable Organic Chemicals by Fish from Oil Sands Process-Affected Water (OSPW).

Uptake and effects of ionizable organic chemicals (IOCs) that are weak acids in aqueous solution by fish can differ as a function of pH. While the pH-dependent behavior of select IOCs is well-understood, complex mixtures of IOCs, e.g., from oil sands process-affected water (OSPW), have not yet been studied systematically. Here, we established an in vitro screening method using the rainbow trout gill cell line, RTgill-W1, to investigate pH-dependent cytotoxicity and permeation of IOCs across cultured epithelia using ultra-high-performance liquid chromatography with high-resolution mass spectrometry (UPLC-HRMS). The assay was benchmarked using model chemicals and technical mixtures, and then used to characterize fractions and reconstituted extracts of field-collected OSPW. Significant pH-dependent cytotoxicity of individual IOCs, acidic fractions, and reconstituted extracts of OSPW was observed. In vitro data were in good agreement with data from a 96 h in vivo exposure experiment with juvenile rainbow trout. Permeation of some IOCs from OSPW was mediated by active transport, as revealed by studies in which inhibitors of these active transport mechanisms were applied. We conclude that the RTgill-W1 in vitro assay is useful for the screening of pH-dependent uptake of IOCs in fish, and has applications for in vitro-in vivo extrapolation, and prioritization of chemicals in nontarget screenings.

A Cross-species Quantitative Adverse Outcome Pathway for Activation of the Aryl Hydrocarbon Receptor Leading to Early Life Stage Mortality in Birds and Fishes.

Dioxin-like compounds (DLCs) elicit adverse effects through activation of the aryl hydrocarbon receptor (AHR). Prior investigations demonstrated that sensitivity to activation of AHR1 in an in vitro AHR transactivation assay is predictive of early life stage mortality among birds. The present study investigated the link between sensitivity to activation of AHR1s and AHR2s and early life stage mortality among fishes. A significant, linear relationship was demonstrated between sensitivity to activation of AHR2 and early life stage mortality among nine fishes, while no relationship was found for AHR1. The slope and y-intercept for the linear relationship between sensitivity to activation of AHR1 and early life stage mortality in birds was not statistically different from the same relationship for AHR2 in fishes. Data for fishes and birds across DLCs were expanded into four significant, linear regression models describing the relationship between sensitivity to activation of AHR and the dose to cause early life stage mortality of 0%, 10%, 50%, or 100%. These four relationships were combined to form a quantitative adverse outcome pathway which can predict dose-response curves of early life stage mortality for DLCs to any bird or fish from species- and chemical-specific responses in an in vitro AHR transactivation assay.

Combining High-Throughput Sequencing of sedaDNA and Traditional Paleolimnological Techniques To Infer Historical Trends in Cyanobacterial Communities.

Freshwaters worldwide are under increasing pressure from anthropogenic activities and changing climate. Unfortunately, many inland waters lack sufficient long-term monitoring to assess environmental trends. Analysis of sedimentary ancient DNA ( sedaDNA) is emerging as a means to reconstruct the past occurrence of microbial communities of inland waters. The purpose of this study was to assess a combination of high-throughput sequencing (16S rRNA) of sedaDNA and traditional paleolimnological analyses to explore multidecadal relationships among cyanobacterial community composition, the potential for cyanotoxin production, and paleoenvironmental proxies. DNA was extracted from two sediment cores collected from a northern Canadian Great Plains reservoir. Diversity indices illustrated significant community-level changes since reservoir formation. Furthermore, higher relative abundances in more recent years were observed for potentially toxic cyanobacterial genera including Dolichospermum. Correlation-based network analysis revealed this trend significantly and positively correlated to abundances of the microcystin synthetase gene ( mcyA) and other paleoproxies (nutrients, pigments, stanols, sterols, and certain diatom species), demonstrating synchrony between molecular and more standard proxies. These findings demonstrate a novel approach to infer long-term dynamics of cyanobacterial diversity in inland waters and highlight the power of high-throughput sequencing to reconstruct trends in environmental quality and inform lake and reservoir management and monitoring program design.

Identification of Chemicals that Cause Oxidative Stress in Oil Sands Process-Affected Water.

Oil sands process-affected water (OSPW) has been reported to cause oxidative stress in organisms, yet the causative agents remain unknown. In this study, a high-throughput in vitro Nrf2 reporter system was used, to determine chemicals in OSPW that cause oxidative stress. Five fractions, with increasing polarity, of the dissolved organic phase of OSPW were generated by use of solid phase extraction cartridges. The greatest response of Nrf2 was elicited by F2 (2.7 ± 0.1-fold), consistent with greater hydroperoxidation of lipids in embryos of Japanese medaka (Oryzias latipes) exposed to F2. Classic naphthenic acids were mainly eluted in F1, and should not be causative chemicals. When F2 was fractionated into 60 subfractions by use of HPLC, significant activation of Nrf2 was observed in three grouped fractions: F2.8 (1.30 ± 0.01-fold), F2.16 (1.34 ± 0.05-fold), and F2.25 (1.28 ± 0.15-fold). 54 compounds were predicted to be potential chemicals causing Nrf2 response, predominated by SO3+ and O3+ species. By use of high-resolution MS2 spectra, these SO3+ and O3+ species were identified as hydroxylated aldehydes. This study demonstrated that polyoxygenated chemicals, rather than classic NAs, were the major chemicals responsible for oxidative stress in the aqueous phase of OSPW.

Toxicokinetics and toxicodynamics of chlorpyrifos is altered in embryos of Japanese medaka exposed to oil sands process-affected water: evidence for inhibition of P-glycoprotein.

Oil sands process-affected water (OSPW) is generated during extraction of bitumen in the surface mining oil sands industry in Alberta, Canada. Studies were performed in vitro by use of Caco-2 cells, and in vivo with larvae of Japanese medaka (Oryzias latipes) to determine if organic compounds from the aqueous phase of OSPW inhibit ATP binding cassette protein ABCB1 (permeability-glycoprotein, P-gp). Neutral and basic fractions of OSPW inhibited activity of P-gp in Caco-2 cells by 1.9- and 2.0-fold, respectively, while the acidic fraction had the least effect. The organophosphate pesticides chlorpyrifos (a substrate of P-gp) and malathion (not a substrate of P-gp), were used as model chemicals to investigate inhibition of P-gp in larvae. Co-exposure to chlorpyrifos and an extract of OSPW containing basic and neutral compounds reduced survival of larvae to 26.5% compared to survival of larvae exposed only to chlorpyrifos, which was 93.7%. However, co-exposure to malathion and the extract of OSPW did not cause acute lethality compared to exposure only to malathion. Accumulation and bioconcentration of chlorpyrifos, but not malathion, was greater in larvae co-exposed with the extract of OSPW. The terminal elimination half-life of chlorpyrifos in larvae exposed to chlorpyrifos in freshwater was 5 days compared with 11.3 days in larvae exposed to chlorpyrifos in OSPW. Results suggest that in non-acute exposures, basic and neutral organic compounds in the water-soluble fraction of OSPW inhibit activity of P-gp, which suggests that OSPW has the potential to cause adverse effects by chemosensitization. Copyright © 2016 John Wiley & Sons, Ltd.

Bioconcentration of Dissolved Organic Compounds from Oil Sands Process-Affected Water by Medaka (Oryzias latipes): Importance of Partitioning to Phospholipids.

The complex mixture of dissolved organics in oil sands process-affected water (OSPW) is acutely lethal to fish at environmentally relevant concentrations, but few bioconcentration factors (BCFs) have been measured for its many chemical species. Japanese medaka (Oryzias latipes) were exposed to 10% OSPW, and measured BCFs were evaluated against predicted BCFs from octanol-water distribution ratios (DOW) and phospholipid membrane-water distribution ratios (DMW). Two heteroatomic chemical classes detected in positive ion mode (SO(+), NO(+)) and one in negative mode (O2(-), also known as naphthenic acids) had the greatest DMW values, as high as 10 000. Estimates of DMW were similar to and correlated with DOW for O(+), O2(+), SO(+), and NO(+) chemical species, but for O2(-) and SO2(-) species the DMW values were much greater than the corresponding DOW, suggesting the importance of electrostatic interactions for these ionizable organic acids. Only SO(+), NO(+), and O2(-) species were detectable in medaka exposed to OSPW, and BCFs for SO(+) and NO(+) species ranged from 0.6 to 28 L/kg, lower than predicted (i.e., 1.4-1.7 × 10(3) L/kg), possibly because of biotransformation of these hydrophobic substances. BCFs of O2(-) species ranged from 0.7 to 53 L/kg, similar to predicted values and indicating that phospholipid partitioning was an important bioconcentration mechanism.

Effect of Lipid Partitioning on Predictions of Acute Toxicity of Oil Sands Process Affected Water to Embryos of Fathead Minnow (Pimephales promelas).

Dissolved organic compounds in oil sands process affected water (OSPW) are known to be responsible for most of its toxicity to aquatic organisms, but the complexity of this mixture prevents use of traditional bottom-up approaches for predicting toxicities of mixtures. Therefore, a top-down approach to predict toxicity of the dissolved organic fraction of OSPW was developed and tested. Accurate masses (i.e., m/z) determined by ultrahigh resolution mass spectrometry in negative and positive ionization modes were used to assign empirical chemical formulas to each chemical species in the mixture. For each chemical species, a predictive measure of lipid accumulation was estimated by stir-bar sorptive extraction (SBSE) to poly(dimethyl)siloxane, or by partitioning to solid-supported lipid membranes (SSLM). A narcosis mode of action was assumed and the target-lipid model was used to estimate potencies of mixtures by assuming strict additivity. A model developed using a combination of the SBSE and SSLM lipid partitioning estimates, whereby the accumulation of chemicals to neutral and polar lipids was explicitly considered, was best for predicting empirical values of LC50 in 96-h acute toxicity tests with embryos of fathead minnow (Pimephales promelas). Model predictions were within 4-fold of observed toxicity for 75% of OSPW samples, and within 8.5-fold for all samples tested, which is comparable to the range of interlaboratory variability for in vivo toxicity testing.

Peroxisome Proliferator-Activated Receptor γ is a Sensitive Target for Oil Sands Process-Affected Water: Effects on Adipogenesis and Identification of Ligands.

Identification of toxic components of complex mixtures is a challenge. Here, oil sands process-affected water (OSPW) was used as a case study to identify those toxic components with a known protein target. Organic chemicals in OSPW exhibited dose-dependent activation of peroxisome proliferator-activated receptor γ (PPARγ) at concentrations less than those currently in the environment (0.025× equivalent of full-strength OSPW), by use of a luciferase reporter gene assay. Activation of PPARγ-mediated adipogenesis by OSPW was confirmed in 3T3L1 preadipocytes, as evidenced by accumulation of lipids and up-regulation of AP2, LPL, and PPARγ gene expression after exposure to polar fractions of OSPW. Unexpectedly, the nonpolar fractions of OSPW inhibited differentiation of preadipocytes via activation of the Wnt signaling pathway. Organic chemicals in OSPW that were ligands of PPARγ were identified by use of a pull-down system combined with untargeted chemical analysis (PUCA), with a recombinant PPARγ protein. Thirty ligands of PPARγ were identified by use of the PUCA assay. High resolution MS(1) and MS(2) spectra were combined to predict the formulas or structures of a subset of ligands, and polyoxygenated or heteroatomic chemicals, especially hydroxylated carboxylic/sulfonic acids, were the major ligands of PPARγ.

Combined Transcriptomic and Proteomic Approach to Identify Toxicity Pathways in Early Life Stages of Japanese Medaka (Oryzias latipes) Exposed to 1,2,5,6-Tetrabromocyclooctane (TBCO).

Currently, the novel brominated flame retardant 1,2,5,6-tetrabromocyclooctane (TBCO) is considered a potential replacement for hexabromocyclododecane (HBCD). Therefore, use of TBCO could increase in the near future. To assess potential toxicological risks to aquatic organisms, embryos of Japanese medaka (Oryzias latipes) were exposed to 10, 100, or 1000 µg/L TBCO from 2 h postfertilization until 1 day post-hatch. TBCO accumulated in embryos in the order of 0.43-1.3 × 10(4)-fold, and the rate constant of accumulation was 1.7-1.8 per day. The number of days to hatch and the hatching success of embryos exposed to the medium and the greatest concentrations of TBCO were impaired. Responses of the transcriptome (RNA-seq) and proteome were characterized in embryos exposed to 100 µg/L TBCO because this was the least concentration of TBCO that caused an effect on hatching. Consistent with effects on hatching, proteins whose abundances were reduced by exposure to TBCO were enriched in embryo development and hatching pathways. Also, on the basis of the responses of transcriptome and proteome, it was predicted that TBCO might impair vision and contraction of cardiac muscle, respectively, and these effects were confirmed by targeted bioassays. This study provided a comprehensive understanding of effects of TBCO on medaka at early life stages and illustrated the power of "omics" to explain and predict phenotypic responses to chemicals.

High Conservation in Transcriptomic and Proteomic Response of White Sturgeon to Equipotent Concentrations of 2,3,7,8-TCDD, PCB 77, and Benzo[a]pyrene.

Adverse effects associated with exposure to dioxin-like compounds (DLCs) are mediated primarily through activation of the aryl hydrocarbon receptor (AHR). However, little is known about the cascades of events that link activation of the AHR to apical adverse effects. Therefore, this study used high-throughput, next-generation molecular tools to investigate similarities and differences in whole transcriptome and whole proteome responses to equipotent concentrations of three agonists of the AHR, 2,3,7,8-TCDD, PCB 77, and benzo[a]pyrene, in livers of a nonmodel fish, the white sturgeon (Acipenser transmontanus). A total of 926 and 658 unique transcripts were up- and down-regulated, respectively, by one or more of the three chemicals. Of the transcripts shared by responses to all three chemicals, 85% of up-regulated transcripts and 75% of down-regulated transcripts had the same magnitude of response. A total of 290 and 110 unique proteins were up- and down-regulated, respectively, by one or more of the three chemicals. Of the proteins shared by responses to all three chemicals, 70% of up-regulated proteins and 48% of down-regulated proteins had the same magnitude of response. Among treatments there was 68% similarity between the global transcriptome and global proteome. Pathway analysis revealed that perturbed physiological processes were indistinguishable between equipotent concentrations of the three chemicals. The results of this study contribute toward more completely describing adverse outcome pathways associated with activation of the AHR.

Linking Oxidative Stress and Magnitude of Compensatory Responses with Life-Stage Specific Differences in Sensitivity of White Sturgeon (Acipenser transmontanus) to Copper or Cadmium.

Sensitivity of white sturgeon (Acipenser transmontanus) to copper (Cu) or cadmium (Cd) has been shown to significantly differ as a function of life-stage. This study investigated oxidative stress, metal homeostasis, and associated compensatory responses as potential mechanisms of this sensitivity pattern in three early life-stages. Sturgeon were most sensitive to Cu at 15 days post hatch (dph), which was accompanied by a significant increase in lipid peroxidation (LPO). Genes involved with amelioration of oxidative stress were significantly less inducible at this stage than in older, less sensitive fry. At 48 dph, acute lethality of sturgeon exposed to Cd was greatest and body LPO was significantly induced by 3.5-fold at 5 µg Cd/L. Moreover, there was a small but significant increase in antioxidative responses. At 139 dph, sturgeon were most tolerant to Cu and Cd and accumulation of these metals was least. Also, expression of metallothionein (MT) and apoptotic genes were greatest while expression of metal transporters was reduced and concentration of LPO was not different from controls. Our results suggest that life-stage specific sensitivity of white sturgeon to metals is complex, encompassing differences in the ability to mount compensatory responses important for metal homeostasis and combating oxidative stress and concomitant damages.

Untargeted Screening and Distribution of Organo-Bromine Compounds in Sediments of Lake Michigan.

Previously unreported natural and synthetic organo-bromine compounds (NSOBCs) have been found to contribute more than 99% of total organic bromine (TOB) in environmental matrices. We recently developed a novel untargeted method (data-independent precursor isolation and characteristic fragment, DIPIC-Frag) and identified ∼2000 NSOBCs in two sediments from Lake Michigan. In this study, this method was used to investigate the distributions of these NSOBCs in 23 surficial samples and 24 segments of a sediment core from Lake Michigan. NSOBCs were detected in all 23 surficial samples and exhibited 10- to 100-fold variations in peak abundance among locations. The pattern of distributions of NSOBCs was correlated with depth of the water column (r(2) = 0.61, p < 0.001). Hierarchical cluster analysis showed that sediments in close proximity exhibited similar profiles of NSOBCs. Distributions of NSOBCs in 24 segments of a sediment core dated from 1766 to 2008 were investigated, and samples from similar depths exhibited similar profiles of NSOBCs. NSOBCs were grouped into four clusters (soft-cluster analysis) with different temporal trends of abundances. 515 and 768 of the NSOBCs were grouped into cluster 1 and cluster 3 with increasing temporal trends, especially since 1950, indicating that abundances of these compounds might have been affected by human activities.

Untargeted Screening and Distribution of Organo-Iodine Compounds in Sediments from Lake Michigan and the Arctic Ocean.

The majority of halogenated organic compounds present in the environment remain unidentified. To address this data gap, we recently developed an untargeted method (data-independent precursor isolation and characteristic fragment; DIPIC-Frag) for identification of unknown organo-bromine compounds. In this study, the method was adapted to enable untargeted screening of natural and synthetic organo-iodine compounds (NSOICs) in sediments. A total of 4,238 NSOIC peaks were detected in sediments from Lake Michigan. Precursor ions and formulas were determined for 2,991 (71%) of the NSOIC peaks. These compounds exhibited variations in abundances (<10(3) to ∼10(7)), m/z values (206.9304-996.9474), retention times (1.0-29.7 min), and number of iodine atoms (1-4). Hierarchical cluster analysis showed that sediments in closer proximity exhibited similar profiles of NSOICs. NSOICs were screened in 10 samples of sediment from the Arctic Ocean to compare the profiles of NSOICs between freshwater and marine sediments. A total of 3,168 NSOIC peaks were detected, and profiles of NSOICs in marine sediments were clearly distinct from Lake Michigan. The coexistence of brominated and iodinated analogues indicated that some NSOICs are of natural origin. Different ratios of abundances of iodinated compounds to brominated analogues were observed and proposed as a marker to distinguish sources of NSOICs.

Is hepatic oxidative stress a main driver of dietary selenium toxicity in white sturgeon (Acipenser transmontanus)?

Most species of sturgeon have experienced significant population declines and poor recruitment over the past decades, leading many, including white sturgeon (Acipenser transmontanus), to be listed as endangered. Reasons for these declines are not yet fully understood but benthic lifestyle, longevity, and delayed sexual maturation likely render sturgeon particularly susceptible to factors such as habitat alteration and contaminant exposures. One contaminant of particular concern to white sturgeon is selenium (Se), especially in its more bioavailable form selenomethionine (SeMet), as it is known to efficiently bioaccumulate in prey items of this species. Studies have shown white sturgeon to be among the most sensitive species of fish to dietary SeMet as well as other pollutants such as metals, dioxin-like chemicals and endocrine disrupters. One of the primary hypothesized mechanisms of toxicity of SeMet in fish is oxidative stress; however, little is know about the specific mode by which SeMet affects the health of white sturgeon. Therefore, the aim of this study was to characterize oxidative stress and associated antioxidant responses as a molecular event of toxicity, and to link it with the pathological effects observed previously. Specifically, three-year-old white sturgeon were exposed for 72 days via their diet to 1.4, 5.6, 22.4 or 104.4µg Se per g feed (dm). Doses were chosen to range over a necessary Se intake level, current environmentally relevant intakes and an intake representing predicted increases of Se release. Lipid hydroperoxides, which are end products of lipid oxidation, were quantified as a marker of oxidative stress. Changes in gene expression of glutathione peroxidase (GPx), superoxide dismutase, catalase, glutathione S-transferase, apoptosis inducing factor and caspase 3 were quantified as markers of the response to oxidative stress. Concentrations of lipid hydroperoxides were highly variable within dose groups and no dose response was observed. GPx expression was significantly increased in the low dose group indicating an induced antioxidant response. Expression of other genes were not significantly induced or suppressed. Overall, there was very little evidence of oxidative stress, and therefore, in contrast to previous reports on other species of teleost fishes, oxidative stress is not believed to be a main driver of toxicity in white sturgeon exposed to SeMet.