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The Adverse Outcome Pathway (AOP) framework represents a valuable conceptual tool to systematically integrate existing toxicological knowledge from a mechanistic perspective to facilitate predictions of chemical-induced effects across species. However, its application for decision-making requires the transition from qualitative to quantitative AOP (qAOP). Here we used a fish model and the synthetic glucocorticoid beclomethasone dipropionate (BDP) to investigate the role of chemical-specific properties, pharmacokinetics, and internal exposure dynamics in the development of qAOPs. We generated a qAOP network based on drug plasma concentrations and focused on immunodepression, skin androgenisation, disruption of gluconeogenesis and reproductive performance. We showed that internal exposure dynamics and chemical-specific properties influence the development of qAOPs and their predictive power. Comparing the effects of two different glucocorticoids, we highlight how relatively similar in vitro hazard-based indicators can lead to different in vivo risk. This discrepancy can be predicted by their different uptake potential, pharmacokinetic (PK) and pharmacodynamic (PD) profiles. We recommend that the development phase of qAOPs should include the application of species-specific uptake and physiologically-based PK/PD models. This integration will significantly enhance the predictive power, enabling a more accurate assessment of the risk and the reliable transferability of qAOPs across chemicals.

There is a growing interest in evaluating the presence of pharmaceutical residues and their metabolites in aquatic biota. In this study, twenty pharmaceuticals, including carbamazepine (CBZ) and two metabolites, were analyzed in homogenates of two fish species (Gambusia affinis and Jenynsia multidentata) captured in polluted areas of the Suquía River (Córdoba, Argentina). The twenty target pharmaceuticals were found in G. affinis, while only fifteen were detected in J. multidentata. We observed a noticeable difference in the accumulation pattern of both fish species, suggesting different pathways for the bioaccumulation of polar pharmaceuticals in each fish. In order to investigate uptake and tissue distribution of pharmaceuticals, a detailed study was performed under controlled laboratory conditions in J. multidentata, exposed to CBZ. CBZ and two of its metabolites (carbamazepine-10,11-epoxide – CBZ-EP and 2-hydroxycarbamazepine – 2-OH-CBZ) were monitored in five organs of fish under laboratory exposure. To our knowledge, this is the first report on the presence of CBZ and its metabolite 2-OH-CBZ in gills, intestine, liver, brain and muscle of fish, while the metabolite carbamazepine-10,11-epoxide (CBZ-EP) was detected in gills and muscle. A ratio CBZ-EP/CBZ close to 0.1 suggests that gills and muscle of J. multidentata could metabolize CBZ through the CBZ-EP pathway. Our results reinforce the need of analyzing multiple species to account for the environmental impact of pollutants, negating the simplification of a single, “representative model” during ecotoxicological biomonitoring. To our knowledge, the biotransformation of CBZ to its metabolites (CBZ-EP, 2-OH-CBZ) in fish, under controlled laboratory in vivo exposures, is reported for the first time.

Psychoactive drugs are frequently detected in the aquatic environment. The evolutionary conservation of the molecular targets of these drugs in fish suggests that they may elicit mode of action–mediated effects in fish as they do in humans, and the key open question is at what exposure concentrations these effects might occur. In the present study, the authors investigated the uptake and tissue distribution of the benzodiazepine oxazepam in the fathead minnow (Pimephales promelas) after 28 d of waterborne exposure to 0.8 μg L−1, 4.7 μg L−1, and 30.6 μg L−1. Successively, they explored the relationship between the internal concentrations of oxazepam and the effects on fish exploratory behavior quantified by performing 2 types of behavioral tests, the novel tank diving test and the shelter‐seeking test. The highest internal concentrations of oxazepam were found in brain, followed by plasma and liver, whereas muscle presented the lowest values. Average concentrations measured in the plasma of fish from the 3 exposure groups were, respectively, 8.7 ± 5.7 μg L−1, 30.3 ± 16.1 μg L−1, and 98.8 ± 72.9 μg L−1. Significant correlations between plasma and tissue concentrations of oxazepam were found in all 3 groups. Exposure of fish to 30.6 µg L−1 in water produced plasma concentrations within or just below the human therapeutic plasma concentration (HTPC) range in many individuals. Statistically significant behavioral effects in the novel tank diving test were observed in fish exposed to 4.7 μg L−1. In this group, plasma concentrations of oxazepam were approximately one‐third of the lowest HTPC value. No significant effects were observed in fish exposed to the lowest and highest concentrations. The significance of these results is discussed in the context of the species‐specific behavior of fathead minnow and existing knowledge of oxazepam pharmacology. Environ Toxicol Chem 2016;35:2782–2790. © 2016 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.

We used a short-term microcosm approach to investigate the influence of two different subinhibitory concentrations of ciprofloxacin (0.01 and 0.1 μg/ml) on both the abundance of a plasmid-mediated quinolone resistance determinant (qnrS) and the structure and composition of bacterial communities from impaired and pristine water supply reservoirs. The results showed that the abundance of the qnrS gene increases in water samples exposed to both subinhibitory concentrations of ciprofloxacin, especially in water samples from La Llosa del Cavall, which represents the pristine system. Subinhibitory ciprofloxacin concentrations also induced changes in bacterial community composition as indicated by the relative abundances of each operational taxonomic unit (OTU) across treatments. Therefore, our findings may be of significant importance because subinhibitory ciprofloxacin concentrations may promote antibiotic resistance and affect bacterial community composition in environmental settings.

In many arid and semi-arid systems, biological communities in river ecosystems are submitted to flow interruption and desiccation, as well as to the impact of urban wastewaters. In this work, we studied (using a LC-LTQ-Orbitrap) the metabolomic response of biofilm communities exposed to both hydrological and chemical stressors. Fluvial biofilms were exposed to a mixture of 9 pharmaceuticals at a total concentration of 5000ng/L (mimicking concentrations and compounds found in polluted aquatic environments) and/or to seven days of desiccation, under laboratory conditions. The biosynthesis of fatty acids was the main metabolic pathway disrupted in biofilms. Endogenous biofilm's metabolites (metabolome) altered due to these stressors were identified. The metabolites that significantly changed only due to one of the stressors could be proposed as potential specific biomarkers. A biomarker of pharmaceutical exposure was the lysophosphatidic acid, which decreased a 160%, while for desiccation stearidonic acid (increased 160%), 16-Oxohexadecanoic acid (increased 340%) and palmitoleic acid (decreased 290%) were the biomarkers proposed. Besides, other metabolites showed different responses depending on the treatment, such as palmitic acid, linolenic acid, behenic acid, lignoceric acid and azelaic acid. The Carbon:Phosphorus (C:P) molar ratio increased due to all stress factors, whereas the algal community composition changed mainly due to desiccation. A possible relationship between those changes observed in structural parameters and the metabolome of biofilms was explored. Overall, our findings support the use of metabolomics to unravel at molecular level the effects from chemical and physical stressors on complex microbial communities, such as biofilms, and pinpoint biomarkers of exposure.

Recent species-extrapolation approaches to the prediction of the potential effects of pharmaceuticals present in the environment on wild fish are based on the assumption that pharmacokinetics and metabolism in humans and fish are comparable. To test this hypothesis, we exposed fathead minnows to the opiate pro-drug tramadol and examined uptake from the water into the blood and brain and the metabolism of the drug into its main metabolites. We found that plasma concentrations could be predicted reasonably accurately based on the lipophilicity of the drug once the pH of the water was taken into account. The concentrations of the drug and its main metabolites were higher in the brain than in the plasma, and the observed brain and plasma concentration ratios were within the range of values reported in mammalian species. This fish species was able to metabolize the pro-drug tramadol into the highly active metabolite O-desmethyl tramadol and the inactive metabolite N-desmethyl tramadol in a similar manner to that of mammals. However, we found that concentration ratios of O-desmethyl tramadol to tramadol were lower in the fish than values in most humans administered the drug. Our pharmacokinetic data of tramadol in fish help bridge the gap between widely available mammalian pharmacological data and potential effects on aquatic organisms and highlight the importance of understanding drug uptake and metabolism in fish to enable the full implementation of predictive toxicology approaches.

This study was aimed to determine the abundance of four antibiotic resistance genes (blaTEM, ermB, qnrS and sulI), as well as bacterial community composition associated with the intestinal mucus of wild freshwater fish species collected from the Foix and La Llosa del Cavall reservoirs, which represent ecosystems with high and low anthropogenic disturbance, respectively. Water and sediments from these reservoirs were also collected and analyzed to determine the pollution level by antibiotics. The blaTEM gene was only detected in brown trout and Ebro barbel, which were collected from La Llosa del Cavall reservoir. In contrast, the sulI and qnrS genes were only detected in common carp, which were collected from the Foix reservoir. Although the ermB gene was also detected in common carp, the values were below the limit of quantification. Likewise, water and sediment samples from the Foix reservoir had higher concentrations and more classes of antibiotics than those from La Llosa del Cavall. Pyrosequencing analysis of 16S rRNA genes revealed significant differences in bacterial communities associated with the intestinal mucus of fish species. Therefore, these findings suggest that anthropogenic activities are not only increasing the pollution of aquatic environments, but also contributing to the emergence and spread of antibiotic resistance in organisms that inhabit such environments.

Fish are good indicators of aquatic environment pollution because of their capability to uptake pollutants contained in water. Therefore, accumulation of pharmaceutical compounds in freshwater and marine fish and other aquatic organisms has been studied extensively in the last decade. In this context, the present study investigates the occurrence of pharmaceutical compounds in wild fish from 25 polluted river sites in the USA, downstream from wastewater treatment plants (WWTPs). Sample sites constitute a subset of urban rivers investigated in the U.S. EPA's 2008–2009 National Rivers and Streams Assessment. Thirteen pharmaceuticals (out of the twenty compounds analyzed) were quantified in fish fillets at concentrations commonly below 10ngg−1, in accordance with the findings from previous studies in the USA and Europe. The psychoactive drugs venlafaxine, carbamazepine and its metabolite 2-hydroxy carbamazepine were the most prevalent compounds (58%, 27% and 42%, respectively). This group of drugs is highly prescribed and rather resistant to degradation during conventional treatment in WWTPs as well as in natural aquatic environments. Salbutamol, a drug used to treat asthma, and the diuretic hydrochlorothiazide were also frequently detected (in >20% of the samples). Occurrence of six pharmaceutical families due to chronic exposure at environmental concentrations in water was detected in eight fish species.

This study investigated the occurrence of 135 contaminants of emerging concern (CECs) – pharmaceuticals, pesticides, a set of endocrine disrupting compounds (EDCs) (parabens, bisphenols, hormones, triazoles, organophosphorus flame retardants and triclosan), UV-filters, perfluoroalkyl substances (PFASs) and halogenated flame retardants (HFRs) – in 59 fish samples, collected in 2010 in 4 Spanish Rivers (Guadalquivir, Júcar, Ebro and Llobregat). Of the 135 CECs, 76 including 8 pharmaceuticals, 25 pesticides, 10 EDCs, 5 UV-filters, 15 PFASs and 13 HFRs were detected. Pharmaceuticals were the less frequently found and at lower concentrations. Pesticides, EDCs, UV-filters, PFASs and HFRs were detected more frequently (>50% of the samples). The maximum concentrations were 15 ng/g dry weight (dw) for pharmaceuticals (diclofenac), 840 ng/g dw for pesticides (chlorpyrifos), 224 ng/g dw for EDCs (bisphenol A), 242 ng/g dw for UV-filters (EHMC), 1738 ng/g dw for PFASs (PFHxA) and 64 ng/g dw for HFRs (Dec 602). The contaminants detected in fish are commonly detected also in sediments. In light of current knowledge, the risk assessment revealed that there was no risk for humans related to the exposure to CECs via freshwater fish consumption. However, results provide detailed information on the mixtures of CECs accumulated that would be very useful to identify their effects on aquatic biota.

Marine calcifiers are amongst the most vulnerable organisms to ocean acidification due to reduction in the availability of carbonate ions for skeletal/shell deposition. However, there are limited long-term studies on the possible impacts of increased pCO2 on these taxa. A 7month CO2 perturbation experiment was performed on one of the most calcium carbonate dependent species, the Antarctic brachiopod Liothyrella uva, which inhabits the Southern Ocean where carbonate ion saturation levels are amongst the lowest on Earth. The effects of the predicted environmental conditions in 2050 and 2100 on the growth rate and ability to repair shell in L. uva were tested with four treatments; a low temperature control (0°C, pH7.98), a pH control (2°C, pH8.05), mid-century scenario (2°C, pH7.75) and end-century scenario (2°C, pH7.54). Environmental change impacts on shell repair are rarely studied, but here repair was not affected by either acidified conditions or temperature. Growth rate was also not impacted by low pH. Elevated temperature did, however, increase growth rates. The ability of L. uva to continue, and even increase shell production in warmer and acidified seawater suggests that this species can acclimate to these combined stressors and generate suitable conditions for shell growth at the site of calcification.

This study investigated the effects of long-term incubation to near-future combined warming (+2 °C) and ocean acidification (−0.3 and −0.5 pH units) stressors, relative to current conditions (−0.3 °C and pH 8.0), on the energetics of food processing in the Antarctic sea urchin, Sterechinus neumayeri. After an extended incubation of 40 months, energy absorbed, energy lost through respiration and lost as waste were monitored through two feeding cycles. Growth parameters (mass of somatic and gonad tissues and the CHN content of gonad) were also measured. There were no significant effects of combined ocean acidification (OA) and temperature stressors on the growth of somatic or reproductive tissue. Despite more food being consumed in the low temperature control, once food processing and maintenance costs were subtracted, there were no significant effects of treatment on the scope for growth. The biggest significant differences were between amounts of food consumed during the two feeding cycles. More food was consumed by the low temperature (0 °C) control animals, indicating a potential effect of the changed conditions on digestive efficiency. Also, in November, more food was consumed, with a higher absorption efficiency, which resulted in a higher scope for growth in November than September and may reflect increased energetic needs associated with a switch to summer physiology. The effect of endogenous seasonal cycles and environmental variability on organism capacity is discussed.

Surface seawaters are becoming more acidic due to the absorption of rising anthropogenic CO2. Marine calcifiers are considered to be the most vulnerable organisms to ocean acidification due to the reduction in the availability of carbonate ions for shell or skeletal production. Rhychonelliform brachiopods are potentially one of the most calcium carbonate-dependent groups of marine organisms because of their large skeletal content. Little is known, however, about the effects of lowered pH on these taxa. A CO2 perturbation experiment was performed on the New Zealand terebratulide brachiopod Calloria inconspicua to investigate the effects of pH conditions predicted for 2050 and 2100 on the growth rate and ability to repair shell. Three treatments were used: an ambient pH control (pH 8.16), a mid-century scenario (pH 7.79), and an end-century scenario (pH 7.62). The ability to repair shell was not affected by acidified conditions with >80% of all damaged individuals at the start of the experiment completing shell repair after 12 weeks. Growth rates in undamaged individuals >3 mm in length were also not affected by lowered pH conditions, whereas undamaged individuals <3 mm grew faster at pH 7.62 than the control. The capability of C. inconspicua to continue shell production and repair under acidified conditions suggests that this species has a robust control over the calcification process, where suitable conditions at the site of calcification can be generated across a range of pH conditions.

Youth with ASD are more likely to experience bullying than their typically developing peers. This risk has not been studied in youth with ASD transitioning to college. We examined the occurrence of bullying in 35 high functioning youth with ASD who were preparing to attend college. We also examined youth anxiety and ASD symptoms. Fifty-one percent of the sample reported being recent victims of bullying; 31% of parents reported their child was a victim of bullying. Parent report of bullying correlated significantly with ratings of youth social anxiety symptoms. These findings suggest that bullying is an issue of concern for higher functioning, older adolescents with ASD, and that their own reports may be particularly important in identifying its occurrence.

This paper is a report of an examination of educational professionals’ perspectives on their decision processes to use a Twitter personal learning network (PLN). When investigating each of the participants’ decision-making processes to accept or reject the use of a Twitter PLN, the externally supported individualized learning experience was integral to the educational professionals’ active decision to adopt the new tool. The five major findings revealed external stimulus and support is (1) vital to address pre-existing attitudes and beliefs, (2) to target the acquisition of technical and implementation knowledge, and (3) to encourage continued exposure, interaction, and exploration. The final two findings focus on the (4) interaction with a social learning community supports decision making and informal learning, and (5) personal experimentation and exploration of a Twitter PLN allows educational professionals to build their professional network, quickly access high quality information, and read educational material. Educational professionals’ informal learning activities were also revealed while using their PLN. Educational professionals reported sharing information and resources with colleagues as having the most significant impact on professional practice. In addition to interviews, the nature of the Twitter platform provided valuable evidence of informal learning activities. These activities reflected in the educational professionals’ tweets included: reading educational subject matter, reflection and collaboration. Also, a new category: Resource Collection was created to reflect the second most popular activity on educational professionals’ Twitter PLN.