Jacob K. Stanley

Determination of select antidepressants in fish from an effluent‐dominated stream

Increasing evidence indicates widespread occurrence of pharmaceuticals and personal care products (PPCPs) in municipal effluent discharges and surface waters. Studies that characterize the fate and effects of PPCPs in aquatic systems are limited, and to our knowledge, data regarding pharmaceutical accumulation in fish of effluent-dominated ecosystems have not been previously reported. In the present study, fish populations were sampled from a reference stream and an effluent-dominated stream in north Texas, USA. Lepomis macrochirus, Ictalurus punctatus, Cyprinus carpio, and Pomoxis nigromaculatus were killed; the liver, brain, and lateral filet tissues dissected; and the tissues stored at -80 degrees C until analysis. Fish tissues were extracted using solid-phase extraction and then analyzed by gas chromatography-mass spectrometry in the negative chemical ionization mode. The selective serotonin reuptake inhibitors (SSRIs) fluoxetine and sertraline and the SSRI metabolites norfluoxetine and desmethylsertraline were detected at levels greater than 0.1 ng/g in all tissues examined from fish residing in a municipal effluent-dominated stream. To our knowledge, the present study is the first report of SSRI residues in fish residing within municipal effluent-dominated systems.

Aquatic ecotoxicology of fluoxetine.

Recent studies indicate that the pharmaceutical fluoxetine, a selective serotonin reuptake inhibitor, is discharged in municipal wastewater treatment plant effluents to surface waters. Few data on environmental fluoxetine exposure and hazard to aquatic life are currently available in the literature. Here, we summarize information on fluoxetine detection in surface waters and review research on single-species toxicity test, Japanese medaka (Oryzias latipes) reproduction and endocrine function, and freshwater mesocosm community responses to fluoxetine exposure. Based on results from our studies and calculations of expected introduction concentrations, we also provide a preliminary aquatic risk characterization for fluoxetine. If standard toxicity test responses and a hazard quotient risk characterization approach are solely considered, little risk of fluoxetine exposure may be expected to aquatic life. However, our findings indicate that: (1) the magnitude, duration and frequency of fluoxetine exposure in aquatic systems requires further investigation; (2) mechanistic toxicity of fluoxetine in non-target biota, including behavioral responses, are clearly not understood; and (3) an assessment of environmentally relevant fluoxetine concentrations is needed to characterize ecological community responses.

Waterborne and sediment toxicity of fluoxetine to select organisms

Ecological risk assessments of pharmaceuticals are currently difficult because little-to-no aquatic hazard and exposure information exists in the peer-reviewed literature for most therapeutics. Recently several studies have identified fluoxetine, a widely prescribed antidepressant, in municipal effluents. To evaluate the potential aquatic toxicity of fluoxetine, single species laboratory toxicity tests were performed to assess hazard to aquatic biota. Average LC(50) values for Ceriodaphnia dubia, Daphnia magna, and Pimephales promelas were 0.756 (234 microg/l), 2.65 (820 microg/l), and 2.28 microM (705 microg/l), respectively. Pseudokirchneriella subcapitata growth and C. dubia fecundity were decreased by 0.044 (14 microg/l) and 0.72 microM (223 microg/l) fluoxetine treatments, respectively. Oryias latipes survival was not affected by fluoxteine exposure up to a concentration of 28.9 microM (8.9 mg/l). An LC(50) of 15.2 mg/kg was estimated for Chironomus tentans. Hyalella azteca survival was not affected up to 43 mg/kg fluoxetine sediment exposure. Growth lowest observed effect concentrations for C. tentans and H. azteca were 1.3 and 5.6 mg/kg, respectively. Our findings indicate that lowest measured fluoxetine effect levels are an order of magnitude higher than highest reported municipal effluent concentrations.

Enantiospecific toxicity of the β-blocker propranolol to Daphnia magna and Pimephales promelas

Propranolol is a widely prescribed, nonselective beta-adrenergic receptor-blocking agent. Propranolol has been detected in municipal effluents from the ng/L to the low-microg/L range. Like many therapeutics and other aquatic contaminants, propranolol is distributed as a racemic mixture ((R,S)-propranolol hydrochloride). Although the (S)-enantiomer is the most active form in mammals (up to 100-fold difference), no information is available regarding the enantiospecific toxicity of propranolol to aquatic organisms. Acute and chronic studies were conducted with Daphnia magna and Pimephales promelas to determine enantiospecific toxicity of propranolol to a model aquatic invertebrate and vertebrate, respectively. Also, enantiospecific effects of propranolol on D. magna heart rate were examined. Propranolol treatment levels were verified using high-performance liquid chromatography/mass spectrometry. Acute (48-h) responses of both organisms were similar for all enantiomer treatments. Chronic P. promelas responses to propranolol enantiomers followed the hypothesized relationship of (S)-propranolol being more toxic than (R)-propranolol, but chronic D. magna responses did not. This is potentially the result of a lack of beta-type receptors in cladocerans. No enantiospecific effects on daphnid heart rate were observed in acute exposures. Interestingly, some propranolol enantiomer treatments produced significant increases in reproduction before causing reproduction to decrease at higher treatment levels. To our knowledge, this research represents the first study of enantiospecific toxicity of chiral pharmaceutical pollutants.

Impact of Organic Carbon on the Stability and Toxicity of Fresh and Stored Silver Nanoparticles

Studies investigating the impact of particle size and capping agents on nanosilver toxicity in pristine laboratory conditions are becoming available. However, the relative importance of known environmental mitigating factors for dissolved silver remains poorly characterized for nanosilver in context with existing predictive toxicity models. This study investigated the implications of freshly prepared versus stored 20 and 100 nm nanosilver stocks to freshwater zooplankton (Ceriodaphnia dubia) in presence and absence of dissolved organic carbon (DOC). Results indicated that while the acute toxicity of nanosilver decreased significantly with larger size and higher DOC, storage resulted in significant increases in toxicity and ion release. The most dramatic decrease in toxicity due to DOC was observed for the 20 nm particle (2.5-6.7 fold decrease), with more modest toxicity reductions observed for the 100 nm particle (2.0-2.4 fold) and dissolved silver (2.7-3.1 fold). While a surface area dosimetry presented an improvement over mass when DOC was absent, the presence of DOC confounded its efficacy. The fraction of dissolved silver in the nanosilver suspensions was most predictive of acute toxicity regardless of system complexity. Biotic Ligand Model (BLM) predictions based on the dissolved fraction in nanosilver suspensions were comparable to observed toxicity.

Assessing the fate and effects of nano aluminum oxide in the terrestrial earthworm, Eisenia fetida

Nano-sized aluminum is currently being used by the military and commercial industries in many applications including coatings, thermites, and propellants. Due to the potential for wide dispersal in soil systems, we chose to investigate the fate and effects of nano-sized aluminum oxide (Al2O3), the oxidized form of nano aluminum, in a terrestrial organism. The toxicity and bioaccumulation potential of micron-sized (50-200 microm, nominal) and nano-sized (11 nm, nominal) Al2O3 was comparatively assessed through acute and subchronic bioassays using the terrestrial earthworm, Eisenia fetida. Subchronic (28-d) studies were performed exposing E. fetida to nano- and micron-sized Al2O3-spiked soils to assess the effects of long-term exposure. No mortality occurred in subchronic exposures, although reproduction decreased at >or=3,000 mg/kg nano-sized Al2O3 treatments, with higher aluminum body burdens observed at 100 and 300 mg/kg; no reproductive effects were observed in the micron-sized Al2O3 treatments. In addition to toxicity and bioaccumulation bioassays, an acute (48-h) behavioral bioassay was conducted utilizing a soil avoidance wheel in which E. fetida were given a choice of habitat between control, nano-, or micron-sized Al2O3 amended soils. In the soil avoidance bioassays, E. fetida exhibited avoidance behavior toward the highest concentrations of micron- and nano-sized Al2O3 (>5,000 mg/kg) relative to control soils. Results of the present study indicate that nano-sized Al2O3 may impact reproduction and behavior of E. fetida, although at high levels unlikely to be found in the environment.

Sediment toxicity and bioaccumulation of nano and micron‐sized aluminum oxide

Nano-aluminum oxide (Al(2)O(3)) is used commercially in coatings and abrasives. Nano-Al(2)O(3) can also be generated through the oxidation of nano-aluminum in military propellants and energetics. The purpose of the present study was to assess toxicity and bioaccumulation of nano-Al(2)O(3) to a variety of sediment organisms (Tubifex tubifex, Hyalella azteca, Lumbriculus variegatus, and Corbicula fluminea). The bioaccumulation and toxicity of nano-Al(2)O(3) was compared with that of micron-sized Al(2)O(3) to investigate potential size-related effects. Results of the present study show species-specific differences in relative bioaccumulation of nano and micron-sized Al(2)O(3). Significant toxic effects (survival and growth) were observed in H. azteca testing, but only at high concentrations unlikely to be found in the environment. Nano-Al(2)O(3) was found to be more toxic than micron-sized Al(2)O(3) to H. azteca survival in a 14-d study in which organisms were in direct contact with a thin layer of 625 or 2,500 mg of Al(2)O(3) dispersed on the surface of either sediment or sand. A significant growth effect was also observed for nano but not micron-sized Al(2)O(3) at the highest treatment level tested (100 g/kg Al(2)O(3)) in a 10-d H. azteca bioassay in which Al(2)O(3) was homogenized with sediment. However, differences in measured sediment Al concentrations (micron-sized = 55.1 [+/-0.6] g/kg Al; nano-sized = 66.2 [+/-0.6] g/kg Al) in the nano and micron-sized Al(2)O(3) preclude direct comparison of the toxicity of these two treatments based on particle size.

Geochemical investigations of metals release from submerged coal fly ash using extended elutriate tests

A storage pond dike failure occurred at the Tennessee Valley Authority Kingston Fossil Plant that resulted in the release of over 3.8 million cubic meters (5 million cubic yards) of fly ash. Approximately half of this material deposited in the main channel of the Emory River, 3.5 km upstream of the confluence of the Emory and Clinch Rivers, Tennessee, USA. Remediation efforts to date have focused on targeted removal of material from the channel through hydraulic dredging, as well as mechanical excavation in some areas. The agitation of the submerged fly ash during hydraulic dredging introduces river water into the fly ash material, which could alter the redox state of metals present in the fly ash and thereby change their sorption and mobility properties. A series of extended elutriate tests were used to determine the concentration and speciation of metals released from fly ash. Results indicated that arsenic and selenium species released from the fly ash materials during elutriate preparation were redox stable over the course of 10d, with dissolved arsenic being present as arsenate, and dissolved selenium being present as selenite. Concentrations of certain metals, such as arsenic, selenium, vanadium, and barium, increased in the elutriate waters over the 10d study, whereas manganese concentrations decreased, likely due to oxidation and precipitation reactions.

Perspectives on Ecological Risk Assessment of Chiral Compounds

Abstract Enantiomers of chiral contaminants can significantly differ in environmental fate as well as in effects. Despite this fact, such differences are often ignored in regulation and in practice, injecting uncertainty into the estimation of risk of chiral compounds. We review the unique challenges posed by stereochemistry to the ecological risk assessment of chiral contaminants and existing regulatory guidance for chiral pharmaceuticals and pesticides in the United States. We identify the advantages of obtaining data on fate and effects of each individual enantiomer of chiral contaminants that are either distributed as or may end up as enantiomer mixtures in the environment due to enantiomerization. Because enantiomers of the same compound are highly likely to coexist in the environment with each other and can result in nonadditive effects, we recommend treatment of enantiomers as components of a mixture using widely accepted mixture models from achiral risk assessment. We further propose the enantiomer hazard ratio for retrospectively characterizing relative enantiomer risk and examine uncertainty factor magnitudes for effects analysis.

Effects of BDE-209 contaminated sediments on zebrafish development and potential implications to human health

Polybrominated diphenyl ethers are compounds widely used as flame-retardants, which are of increasing environmental concern due to their persistence, and potential adverse effects. This study had two objectives. First, we assessed if BDE-209 in sediment was bioavailable and bioaccumulated into zebrafish embryos. Secondly, we assessed the potential impact on human and environmental health of bioavailable BDE-209 using human in vitro cell assays and zebrafish embryos. Zebrafish were exposed from 4h to 8days post-fertilization to sediments spiked with 12.5mg/kg of BDE-209. Zebrafish larvae accumulated ten fold more BDE-209 than controls in unspiked sediment after 8days. BDE-209 impacted expression of neurological pathways and altered behavior of larvae, although BDE-209 had no visible affect on thyroid function or motoneuron and neuromast development. Zebrafish data and in silico predictions suggested that BDE-209 would also interact with key human transcription factors and receptors. We therefore tested these predictions using mammalian in vitro assays. BDE-209 activated human aryl hydrocarbon receptor, peroxisome proliferator activating receptors, CF/b-cat, activator protein 1, Oct-MLP, and the estrogen receptor-related alpha (ERRα) receptor in cell-based assays. BDE-209 also inhibited human acetylcholinesterase activity. The observation that BDE-209 can be bioaccumulated from contaminated sediment highlights the need to consider this as a potential environmental exposure route. Once accumulated, our data also show that BDE-209 has the potential to cause impacts on both human and environmental health.