Surgical and perioperative management of flail chest with titanium plates: a French cohort series from a thoracic referral center.

BACKGROUND: The development of titanium claw plates has made rib osteosynthesis easy to achieve and led to a renewed interest for this surgery. We report the management of patients referred to the intensive care unit (ICU) of a referral center for surgical rib fracture fixation (SRFF) after chest trauma. METHODS: We performed a retrospective observational cohort study describing the patients' characteristics and analyzing the determinants of postoperative complications. RESULTS: From November 2013 to December 2016, 42 patients were referred to our center for SRFF: 12 patients (29%) had acute respiratory failure, 6 of whom received invasive mechanical ventilation. The Thoracic Trauma Severity Score (TTSS) was 11.0 [9-12], with 7 [5-9] broken ribs and a flail chest in 92% of cases. A postoperative complication occurred in 18 patients (43%). Five patients developed ARDS (12%). Postoperative pneumonia occurred in 11 patients (26%). Two patients died in the ICU. In multivariable analysis, the Thoracic Trauma Severity Score (TTSS) (OR = 1.89; CI 95% 1.12-3.17; p = 0.016) and the Simplified Acute Physiology Score II without age (OR = 1.17; CI 95% 1.02-1.34; p = 0.024) were independently associated with the occurrence of a postoperative complication. CONCLUSION: The TTSS score appears to be accurate for determining thoracic trauma severity. Short and long-term benefit of Surgical Rib Fracture Fixation should be assessed, particularly in non-mechanically ventilated patients.

Spatial and seasonal occurrence of semi-volatile organic compounds (SVOCs) in fish influenced by snowmelt and municipal effluent discharge.

In the present study we examined spatial and seasonal trends in the levels of a wide suite of semi-volatile organic compounds (SVOCs) in brown trout (Salmo trutta) and mottled sculpin (Cottus bairdii) in East Canyon Creek, Utah, USA, an effluent-dominated stream during summer months. Fish samples were collected from four sampling sites, including one reference site upstream, and three sites at incremental distances downstream of the effluent discharge over multiple seasons. The samples were analyzed for 218 lipophilic contaminants, including pesticides and their metabolites, polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), and polybrominated diphenyl ethers (PBDEs) and other flame retardants. Some PAHs, pesticides and their metabolites, PCBs, PBDEs and other flame retardants were measured in mottled sculpin (11 analytes) and brown trout (17 analytes). Hexachlorobenzene (HCB), p,p'-DDE, BDE-47 and triphenyl phosphate (TPHP) were the most frequently detected contaminants in mottled sculpin and brown trout, while BDE-47 and p,p'-DDE were measured at the highest concentrations, reaching up to 73 and 19 ng/g wet weight, respectively. Our results indicated that snowmelt did not alter accumulation of the examined lipophilic contaminants, and no consistent seasonal differences were observed in their accumulation. A spatial pattern was observed for PBDE congeners, where lowest levels were measured in fish tissues from a reference site, and highest concentrations were measured in fish collected downstream of the effluent discharge, indicating that municipal effluent discharge contributes to the elevated PBDE levels in fish residing in this effluent-dominated stream. We further calculated screening level consumption risks following United States Environmental Protection Agency (EPA) methods, and identified the importance of considering discharge gradients in effluent-dominated systems during bioaccumulation assessments.

Low dissolved oxygen increases uptake of a model calcium channel blocker and alters its effects on adult Pimephales promelas.

Human population growth accompanied with urbanization is urbanizing the water cycle in many regions. Urban watersheds, particularly with limited upstream dilution of effluent discharges, represent worst case scenarios for exposure to multiple environmental stressors, including down the drain chemicals (e.g., pharmaceuticals) and other stressors (e.g., dissolved oxygen (DO)). We recently identified the calcium channel blocker diltiazem (DZM) to accumulate in fish plasma exceeding human therapeutic doses (e.g., Cmin) in coastal estuaries impaired due to nonattainment of DO water quality standards. Thus, we examined whether DO influences DZM uptake by fish, and if changes in DO-dependent upatke alter fish physiological and biochemical responses. Low DO (3.0 mg DO/L) approximately doubled diltiazem uptake in adult fathead minnows relative to normoxic (8.2 mg DO/L) conditions and were associated with significant (p < 0.05) increases in fish ventilation rate at low DO levels. Decreased burst swim performance (Uburst) of adult fathead minnows were significantly (p < 0.05) altered by low versus normal DO levels. DO × DZM studies reduced Uburst by 13-31% from controls, though not significantly (p = 0.06). Physiological responses in fish exposed to DZM alone were minimal; however, in co-exposure with low DO, decreasing trends in Uburst appeared inversely related to plasma lactate levels. Such physiological responses to multiple stressors, when paired with internal tissue concentrations, identify the utility of employing biological read across approaches to identify adverse outcomes of heart medications and potentially other cardiotoxicants impacting fish cardiovascular function across DO gradients.

Influence of salinity and pH on bioconcentration of ionizable pharmaceuticals by the gulf killifish, Fundulus grandis.

Estuaries routinely receive discharges of contaminants of emerging concern from urban regions. Within these dynamic estuarine systems, salinity and pH can vary across spatial and temporal scales. Our previous research identified bioaccumulation of the calcium channel blocker diltiazem and the antihistamine diphenhydramine in several species of fish residing in multiple urban estuaries along the Gulf of Mexico in Texas, where field-measured observations of diltiazem in fish plasma exceeded human therapeutic plasma doses. However, there remains a limited understanding of pharmaceutical bioaccumulation in estuarine environments. Here, we examined the influence of pH and salinity on bioconcentration of three pharmaceuticals in the Gulf killifish, Fundulus grandis. F. grandis were exposed to low levels of the ionizable pharmaceuticals carbamazepine, diltiazem, and diphenhydramine at two salinities (5 ppt, 20 ppt) and two pH levels (6.7, 8.3). pH influenced bioconcentration of select weak base pharmaceuticals, while salinity did not, suggesting that intestinal uptake via drinking does not appear to be a major exposure route of these pharmaceuticals in killifish. Compared to our previous pH dependent uptake observations with diphenhydramine in the fathead minnow model, killifish apparent volume of distribution values were markedly lower than fatheads, though killifish bioconcentration factors were similar at high pH and four fold higher at low pH than freshwater fish. Advancing an understanding of environmental gradient influences on pharmacokinetics among fish is necessary to improve bioaccumulation assessments and interpretation of toxicological observations for ionizable contaminants.

Determination of microcystins, nodularin, anatoxin-a, cylindrospermopsin, and saxitoxin in water and fish tissue using isotope dilution liquid chromatography tandem mass spectrometry.

Cyanobacteria can form dense blooms under specific environmental conditions, and some species produce secondary metabolites known as cyanotoxins, which present significant risks to public health and the environment. Identifying toxins produced by cyanobacteria present in surface water and fish is critical to ensuring high quality food and water for consumption, and protectionn of recreational uses. Current analytical screening methods typically focus on one class of cyanotoxins in a single matrix and rarely include saxitoxin. Thus, a cross-class screening method for microcystins, nodularin, anatoxin-a, cylindrospermopsin, and saxitoxin was developed to examine target analytes in environmental water and fish tissue. This was done, due to the broad range of cyanotoxin physicochemical properties, by pairing two extraction and separation techniques to improve isolation and detection. For the first time a zwitterionic hydrophilic interaction liquid chromatography column was evaluated to separate anatoxin-a, cylindrospermopsin, and saxitoxin, demonstrating greater sensitivity for all three compounds over previous techniques. Further, the method for microcystins, nodularin, anatoxin-a, and cylindrospermopsin were validated using isotopically labeled internal standards, again for the first time, resulting in improved compensation for recovery bias and matrix suppression. Optimized extractions for water and fish tissue can be extended to other congeners in the future. These improved separation and isotope dilution techniques are a launching point for more complex, non-targeted analyses, with preliminary targeted screening.

Spatial and temporal influence of onsite wastewater treatment systems, centralized effluent discharge, and tides on aquatic hazards of nutrients, indicator bacteria, and pharmaceuticals in a coastal bayou.

In the rapidly urbanizing watersheds and estuaries flowing to the Gulf of Mexico in Texas, USA, instream flows are increasingly influenced by point source and nonpoint source discharges. Spatial and temporal tidal influences on water quality, especially for contaminants of emerging concern (CECs), is poorly understood in estuaries and coastal systems. We selected Dickinson Bayou, an urban estuary in Galveston County, Texas, for study because it has historically impaired water quality, receives point source discharge from one major wastewater treatment plant (WWTP), while also being influenced by high densities of onsite sewage facilities upstream in the watershed. We explored the occurrence and potential hazards of aquatic contaminants, including nutrients, indicator bacteria for pathogens, and CECs, in relation to this point source discharge, across seasons and at high and low tides. Aquatic contaminants and associated hazards varied significantly in relation to the WWTP discharge, and were influenced by onsite systems. In fact, spatiotemporal water quality varied by class of contaminants (e.g., nutrients, indicator bacteria, CECs), which indicates that traditional surface water monitoring activities should account for such environmental complexity. This study provides a diagnostic approach for future studies of emerging water quality challenges across gradients of rapidly urbanizing coastal bays and estuaries.

Pharmaceuticals, illicit drugs and their metabolites in fish from Argentina: Implications for protected areas influenced by urbanization.

Because an understanding of aquatic bioaccumulation of human pharmaceuticals in Latin America is limited, this area was recently identified as a priority environmental quality research need. We examined bioaccumulation of twenty-seven pharmaceuticals, illicit drugs and their metabolites in muscle, liver and gills of multiple fish species (Rhamdia quelen, Hypostomus commersoni, Hoplias lacerdae, Prochilodus lineatus) from an urban river receiving wastewater discharges (Paraná) and a lotic system (Acaraguá) without direct wastewater sources, which runs through a protected area. All samples were analyzed using isotope-dilution liquid chromatography-tandem mass spectrometry. Caffeine, which was detected up to 13 µg/kg, and antibiotics were consistently detected in all fish. Among antibiotics, erythromycin was ubiquitous (0.7-5.6 µg/kg) but its tissue concentrations were lower than levels of sulfamethoxazole, sulfathiazole and trimethoprim (0.9-5.5 µg/kg), which are used in human medicine, aquaculture and livestock. Erythromycin bioaccumulation in fish is reported here from Argentina for the first time, though levels of antibiotics in edible muscles of these species were lower than the maximum residue limits for human consumption. We observed norfluoxetine, the primary active metabolite of the antidepressant fluoxetine, ranging from 1.1-9.1 µg/kg in fish. We further identified benzoylecgonine, a primary metabolite of cocaine, in fish from both study systems, representing the first observation an illicit drug or associated metabolites bioaccumulation in aquatic life from Argentina. Interestingly, high pharmaceutical levels were observed in fish from the Acaraguá river suggesting their transport into the protected area, from the surrounding lands. Though fish from the Paraná river were sampled near WWTP discharges, pharmaceutical concentrations may have been reduced by hydrological and other environmental conditions, and biological differences among species. These findings, which observed bioaccumulation of select pharmaceuticals, their metabolites and illicit drugs in wild fish sampled inside a protected area, highlight the importance of developing an advanced understanding of urban influences on inland protected watersheds.

Influence of Diltiazem on Fathead Minnows Across Dissolved Oxygen Gradients.

Water resources in many arid to semi-arid regions are stressed by population growth and drought. Growing populations and climatic changes are influencing contaminant and water chemistry dynamics in urban inland waters, where flows can be dominated by, or even dependent on, wastewater effluent discharge. In these watersheds, interacting stressors such as dissolved oxygen and environmental contaminants (e.g., pharmaceuticals) have the potential to affect fish physiology and populations. Recent field observations from our group identified the calcium channel blocker (CCB) diltiazem in fish plasma exceeding human therapeutic doses (e.g., Cmin ) in aquatic systems impaired because of nonattainment of dissolved oxygen water quality standards. Therefore our study objectives examined: 1) standard acute and chronic effects of dissolved oxygen and diltiazem to fish, 2) influences of dissolved oxygen at criteria levels deemed protective of aquatic life on diltiazem toxicity to fish, and 3) whether sublethal effects occur at diltiazem water concentrations predicted to cause a human therapeutic level (therapeutic hazard value [THV]) in fish plasma. Dissolved oxygen × diltiazem co-exposures significantly decreased survival at typical stream, lake, and reservoir water quality standards of 5.0 and 3.0 mg dissolved oxygen/L. Dissolved oxygen and diltiazem growth effects were observed at 2 times and 10 times lower than median lethal concentration (LC50) values (1.7 and 28.2 mg/L, respectively). Larval fathead minnow (Pimephales promelas) swimming behavior following low dissolved oxygen and diltiazem exposure generally decreased and was significantly reduced in light-to-dark bursting distance traveled, number of movements, and duration at concentrations as low as the THV. Individual and population level consequences of such responses are not yet understood, particularly in older organisms or other species; however, these findings suggest that assessments with pharmaceuticals and other cardioactive contaminants may underestimate adverse outcomes in fish across dissolved oxygen levels considered protective of aquatic life. Environ Toxicol Chem 2018;37:2835-2850. © 2018 SETAC.

Spatio-temporal bioaccumulation and trophic transfer of ionizable pharmaceuticals in a semi-arid urban river influenced by snowmelt.

Bioaccumulation of pharmaceuticals in aquatic organisms is increasingly reported in the peer-reviewed literature. However, seasonal instream dynamics including occurrence and bioaccumulation across trophic positions are rarely studied, particularly in semiarid streams with flows influenced by seasonal snowmelt and municipal effluent discharges. Thus, we selected East Canyon Creek in Park City, Utah, USA to examine spatio-temporal bioaccumulation of select ionizable pharmaceuticals across trophic positions using trophic magnification factors calculated at incremental distances (0.15, 1.4, 13 miles) downstream from a municipal effluent discharge during spring (May), Summer (August), and fall (October). Nine target analytes were detected in all species during all sampling events. Trophic dilution was consistently observed for amitriptyline, caffeine, diphenhydramine, diltiazem, fluoxetine, and sertraline, regardless of seasonal instream flows or distance from effluent discharge. Calculated TMFs ranged from 0.01-0.71 with negative slopes observed for all regressions of chemical residue in tissue and trophic position. We further presents the first empirical investigation of normalizing pharmaceutical concentrations to lipid, phospholipid or protein fractions using pair matched fish samples. Empirical results identify that normalization of ionizable pharmaceutical residues in aquatic tissues to neutral lipids, polar lipids, or the total protein fraction is inappropriate, though bioaccumulation studies examining influences of internal partitioning (e.g., plasma proteins) are needed.

Comparative behavioral toxicology with two common larval fish models: Exploring relationships among modes of action and locomotor responses.

Behavioral responses inform toxicology studies by rapidly and sensitively detecting molecular initiation events that propagate to physiological changes in individuals. These behavioral responses can be unique to chemical specific mechanisms and modes of action (MOA) and thus present diagnostic utility. In an initial effort to explore the use of larval fish behavioral response patterns in screening environmental contaminants for toxicity and to identify behavioral responses associated with common chemical specific MOAs, we employed the two most common fish models, the zebrafish and the fathead minnow, to define toxicant induced swimming activity alterations during interchanging photoperiods. Though the fathead minnow (Pimephales promelas) is a common model for aquatic toxicology research and regulatory toxicology practice, this model has received little attention in behavioral studies compared to the zebrafish, a common biomedical model. We specifically compared behavioral responses among 7 different chemicals (1-heptanol, phenol, R-(-)-carvone, citalopram, diazinon, pentylenetetrazole (PTZ), and xylazine) that were selected and classified based on anticipated MOA (nonpolar narcosis, polar narcosis, electrophile, specific mechanism) according to traditional approaches to examine whether these comparative responses differ among chemicals with various structure-based predicted toxicity. Following standardized experimental guidelines, zebrafish embryos and fathead minnow larvae were exposed for 96 h to each compound then were observed using digital behavioral analysis. Behavioral observations included photomotor responses, distance traveled, and stimulatory, refractory and cruising locomotor activity. Though fathead minnow larvae displayed greater behavioral sensitivity to 1-heptanol, phenol and citalopram, zebrafish were more sensitive to diazinon and R-(-)-carvone. Both fish models were equally sensitive to xylazine and PTZ. Further, the pharmaceuticals citalopram and xylazine significantly affected behavior at therapeutic hazard values, and each of the seven chemicals elicited unique behavioral response profiles. Larval fish behaviors appear useful as early tier diagnostics to identify mechanisms and pathways associated with diverse biological activities for chemicals lacking mechanistic data.

Transcatheter embolotherapy of pulmonary artery aneurysms as emergency treatment of hemoptysis in Behcet patients: experience of a referral center and a review of the literature.

Hemoptysis is a life-threatening complication of Behcet's disease that is likely related to pulmonary artery aneurysm (PAA). Vascular interventional radiology may offer effective emergency therapeutic option, but has not been thoroughly investigated in this setting. A case series of a French referral center for hemoptysis combined with a literature review of case reports was conducted. Between 1995 and 2016, 12 patients were referred to our center for hemoptysis revealing or complicating the course of Behcet's disease. Pulmonary artery aneurysm (PAA) was the mechanism of hemoptysis in ten patients, nine of whom were treated by a transcatheter embolotherapy. Combining an additional 8 case reports from the literature, 17 patients treated by transcatheter embolotherapy for PAA were analyzed. The duration of the course of Behcet's disease was 22 months [IQR 3-45] at the time of PAA diagnosis. Transcatheter embolotherapy of PAA was successful for immediately controlling hemoptysis in all patients, without major complication except for one. Hemoptysis recurred in seven patients (41%) within 5 months [IQR 1-12]. The use of coils for transcatheter embolotherapy was associated with hemoptysis recurrence. A bronchosystemic hypervascularization related to the previously occluded PAA was the main mechanism of bleeding recurrence, leading to bronchosystemic artery embolization in four patients and surgery in two patients. Behcet's disease-related hemoptysis is mainly due to PAA. Transcatheter embolotherapy should be considered as the first-line emergency treatment for PAA-related hemoptysis, in association with the immunosuppressive regimen. Hemoptysis may recur in half of the cases, involving preferentially a bronchosystemic arterial mechanism.

Differential uptake of and sensitivity to diphenhydramine in embryonic and larval zebrafish.

The zebrafish fish embryo toxicity (FET) test is increasingly employed for alternative toxicity studies, yet our previous research identified increased sensitivity of zebrafish slightly older than embryos employed in FET methods (0-4 d postfertilization [dpf]). We identified rapid steady-state accumulation of diphenhydramine across zebrafish embryo and larval stages. However, significantly (p < 0.05) lower accumulation was observed at 48 h compared to 96 h in chorionated and dechorionated embryos (0-4 dpf), but not in zebrafish at 7 to 11 and 14 to 18 dpf. Increased uptake and toxicity of diphenhydramine was further observed in zebrafish at 7 to 11 and 14 to 18 dpf compared with 0-4 dpf embryos with chorion or dechorionated, which indicates that differential zebrafish sensitivity with age is associated with accumulation resulting from gill and other toxicokinetic and toxicodynamic changes during development. Environ Toxicol Chem 2018;37:1175-1181. © 2017 SETAC.

Pharmaceuticals in water, fish and osprey nestlings in Delaware River and Bay.

Exposure of wildlife to Active Pharmaceutical Ingredients (APIs) is likely to occur but studies of risk are limited. One exposure pathway that has received attention is trophic transfer of APIs in a water-fish-osprey food chain. Samples of water, fish plasma and osprey plasma were collected from Delaware River and Bay, and analyzed for 21 APIs. Only 2 of 21 analytes exceeded method detection limits in osprey plasma (acetaminophen and diclofenac) with plasma levels typically 2-3 orders of magnitude below human therapeutic concentrations (HTC). We built upon a screening level model used to predict osprey exposure to APIs in Chesapeake Bay and evaluated whether exposure levels could have been predicted in Delaware Bay had we just measured concentrations in water or fish. Use of surface water and BCFs did not predict API concentrations in fish well, likely due to fish movement patterns, and partitioning and bioaccumulation uncertainties associated with these ionizable chemicals. Input of highest measured API concentration in fish plasma combined with pharmacokinetic data accurately predicted that diclofenac and acetaminophen would be the APIs most likely detected in osprey plasma. For the majority of APIs modeled, levels were not predicted to exceed 1 ng/mL or method detection limits in osprey plasma. Based on the target analytes examined, there is little evidence that APIs represent a significant risk to ospreys nesting in Delaware Bay. If an API is present in fish orders of magnitude below HTC, sampling of fish-eating birds is unlikely to be necessary. However, several human pharmaceuticals accumulated in fish plasma within a recommended safety factor for HTC. It is now important to expand the scope of diet-based API exposure modeling to include alternative exposure pathways (e.g., uptake from landfills, dumps and wastewater treatment plants) and geographic locations (developing countries) where API contamination of the environment may represent greater risk.

Ontogenetic dietary shifts and bioaccumulation of diphenhydramine in Mugil cephalus from an urban estuary.

Though bioaccumulation of pharmaceuticals has received attention in inland waters, studies of pharmaceutical bioaccumulation in estuarine and marine systems are limited. Further, an understanding of pharmaceutical bioaccumulation across size classes of organisms displaying ontogenetic feeding shifts is lacking. We selected the striped mullet, Mugil cephalus, a euryhaline and eurythermal species that experiences dietary shifts with age, to identify whether a model base, diphenhydramine, accumulated in a tidally influenced urban bayou. We further determined whether diphenhydramine accumulation differed among size classes of striped mullet over a two year study period. Stable isotope analysis identified that ontogenetic feeding shifts of M. cephalus occurred from juveniles to adults. However, bioaccumulation of diphenhydramine did not significantly increase across age classes of M. cephalus but corresponded to surface water levels of the pharmaceutical, which suggests inhalational uptake to diphenhydramine was more important for bioaccumulation than dietary exposure in this urban estuary.

Predicted and observed therapeutic dose exceedances of ionizable pharmaceuticals in fish plasma from urban coastal systems.

Instream flows of the rapidly urbanizing watersheds and estuaries of the Gulf of Mexico in Texas (USA) are increasingly dominated by reclaimed waters. Though ionizable pharmaceuticals have received increasing attention in freshwaters, many research questions remain unanswered, particularly in tidally influenced urban coastal systems, which experience significant spatiotemporal variability in pH that influences bioavailability and bioaccumulation. The authors coupled fish plasma modeling of therapeutic hazard values with field monitoring of water chemistry variability and pharmaceutical occurrence to examine whether therapeutic hazards to fish existed within these urban coastal ecosystems and whether therapeutic hazards differed within and among coastal locations and seasons. Spatial and temporal fluctuations in pH within study sites altered the probability of encountering pharmaceutical hazards to fish. Significant water quality differences were consistently observed among traditional parameters and pharmaceuticals collected from surface and bottom waters, which are rarely sampled during routine surface water quality assessments. The authors then compared modeling predictions of fish plasma concentrations of pharmaceuticals to measured plasma levels from various field-collected fish species. Diphenhydramine and diltiazem were observed in plasma of multiple species, and diltiazem exceeded human therapeutic doses in largemouth bass, catfish, and mullet inhabiting these urban estuaries. Though the present study only examined a small number of target analytes, which represent a microcosm of the exposome of these fish, coastal systems are anticipated to be more strongly influenced by continued urbanization, altered instream flows, and population growth in the future. Unfortunately, aquatic toxicology information for diltiazem and many other pharmaceuticals is not available for marine and estuarine organisms, but such field observations suggest that potential adverse outcomes should be examined.

Bioaccumulation of human pharmaceuticals in fish across habitats of a tidally influenced urban bayou.

Though pharmaceuticals and other contaminants of emerging concern are increasingly observed in inland water bodies, the occurrence and bioaccumulation of pharmaceuticals in estuaries and coastal ecosystems are poorly understood. In the present study, bioaccumulation of select pharmaceuticals and other contaminants of emerging concern was examined in fish from Buffalo Bayou, a tidally influenced urban ecosystem that receives effluent from a major (∼200 million gallons per day) municipal wastewater treatment plant in Houston, Texas, USA. Using isotope dilution liquid chromatography-tandem mass spectrometry, various target analytes were observed in effluent, surface water, and multiple fish species. The trophic position of each species was determined using stable isotope analysis. Fish tissue levels of diphenhydramine, which represented the only pharmaceutical detected in all fish species, did not significantly differ between freshwater and marine fish predominantly inhabiting benthic habitats; however, saltwater fish with pelagic habitat preferences significantly accumulated diphenhydramine to the highest levels observed in the present study. Consistent with previous observations from an effluent-dependent freshwater river, diphenhydramine did not display trophic magnification, which suggests site-specific, pH-influenced inhalational uptake to a greater extent than dietary exposure in this tidally influenced urban ecosystem. The findings highlight the importance of understanding differential bioaccumulation and risks of ionizable contaminants of emerging concern in habitats of urbanizing coastal systems.

Age matters: Developmental stage of Danio rerio larvae influences photomotor response thresholds to diazinion or diphenhydramine.

Because basic toxicological data is unavailable for the majority of industrial compounds, High Throughput Screening (HTS) assays using the embryonic and larval zebrafish provide promising approaches to define bioactivity profiles and identify potential adverse outcome pathways for previously understudied chemicals. Unfortunately, standardized approaches, including HTS experimental designs, for examining fish behavioral responses to contaminants are rarely available. In the present study, we examined movement behavior of larval zebrafish over 7 days (4-10 days post fertilization or dpf) during typical daylight workday hours to determine whether intrinsic activity differed with age and time of day. We then employed an early life stage approach using the Fish Embryo Test (FET) at multiple developmental ages to evaluate whether photomotor response (PMR) behavior differed with zebrafish age following exposure to diazinon (DZN), a well-studied orthophosphate insecticide, and diphenhydramine (DPH), an antihistamine that also targets serotonin reuptake transporters and the acetylcholine receptor. 72h studies were conducted at 1-4, 4-7 and 7-10dpf, followed by behavioral observations using a ViewPoint system at 4, 7 and 10dpf. Distance traveled and swimming speeds were quantified; nominal treatment levels were analytically verified by isotope-dilution LC-MSMS. Larval zebrafish locomotion displayed significantly different (p<0.05) activity profiles over the course of typical daylight and workday hours, and these time of day PMR activity profiles were similar across ages examined (4-10dpf). 10dpf zebrafish larvae were consistently more sensitive to DPH than either the 4 or 7dpf larvae with an environmentally realistic lowest observed effect concentration of 200ng/L. Though ELS and FET studies with zebrafish typically focus on mortality or teratogenicity in 0-4dpf organisms, behavioral responses of slightly older fish were several orders of magnitude more sensitive to DPH. Our observations highlight the importance of understanding the influence of time of day on intrinsic locomotor activity, and the age-specific hazards of aquatic contaminants to fish behavior.

A multibiomarker approach to explore interactive effects of propranolol and fluoxetine in marine mussels.

A multi-biomarker approach, including several lysosomal parameters, activity and mRNA expression of antioxidant enzymes, and DNA damage, was employed to investigate the nominal effects of 0.3 ng/L fluoxetine (FX) and 0.3 ng/L propranolol (PROP) alone or in combination (0.3 ng/L FX + 0.3 ng/L PROP) on Mediterranean mussels after a 7 day treatment. FX co-exposure appears to facilitate PROP bioaccumulation because PROP only accumulated in digestive gland of FX + PROP treated mussels. Lysosomal parameters were significantly impaired by FX + PROP treatment, while no clear antioxidant responses at the catalytic and transcriptional levels were observed. Biomarker responses led to a "medium stress level" diagnosis in FX + PROP treated mussels, according to the Expert System, whereas 0.3 ng/L PROP or FX alone did not induce consistent stress conditions. These findings suggest vulnerability of coastal marine mussels to FX and PROP contamination at environmentally relevant levels.

Pharmaceutical bioaccumulation by periphyton and snails in an effluent-dependent stream during an extreme drought.

Increasing evidence indicates that pharmaceutical bioaccumulate in fish collected downstream from municipal wastewater effluent discharges. However, studies of pharmaceutical bioaccumulation by other aquatic organisms, including primary producers (e.g., periphyton) and grazers (e.g., snails), are lacking in wadeable streams. Here, we examined environmental occurrence and bioaccumulation of a range of pharmaceuticals and other contaminants of emerging concern in surface water, a common snail (Planorbid sp.) and periphyton from an effluent-dependent stream in central Texas, USA, during a historic drought, because such limited dilution and instream flows may represent worst-case exposure scenarios for aquatic life to pharmaceuticals. Water and tissue samples were liquid-liquid extracted and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) with electrospray ionization. Target analytes included 21 pharmaceuticals across multiple drug classes and 2 pharmacologically active metabolites. Several pharmaceuticals were detected at up to 4.7 µg kg(-1) in periphyton and up to 42 µg kg(-1) in Planorbid sp. We then identified limitations of several bioconcentration factor and bioaccumulation factor models, developed for other invertebrates, to assist interpretation of such field results. Observations from the present study suggest that waterborne exposure to pharmaceuticals may be more important than dietary exposure for snails.