45 research outputs found

    Spatial and temporal occurrence of pharmaceuticals in UK estuaries

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    There is a lack of data on the occurrence of pharmaceuticals in estuaries worldwide, with little understanding of their temporal and spatial variations globally. Ibuprofen, paracetamol, diclofenac, trimethoprim and citalopram were measured in twelve estuaries in the UK. Initially, these compounds were monitored in the Humber Estuary, where samples were taken every two months over a twelve month period in order to assess their spatial and temporal variations. Ibuprofen was found at some of the highest concentrations ever measured in an estuary globally (18–6297 ng l−1), with paracetamol also measured at relatively high concentrations (4–917 ng l−1) in comparison to the other compounds. In terms of spatial distribution, a pattern was observed where the highest concentrations were found at a site at which wastewater is discharged, whilst compound concentrations were often lower upstream and downstream of this site. The downstream profile of pharmaceuticals differed temporally with concentrations highest downstream when input from wastewater effluent was highest. Eleven further estuaries were sampled around the UK in order to put the occurrence of pharmaceuticals in the Humber Estuary into a wider context. Pharmaceutical concentrations in the other estuaries sampled were <210 ng l−1 but, again, ibuprofen and paracetamol were found at concentrations higher than other compounds, whereas diclofenac and citalopram were absent in many estuaries. The Humber, which is the receiving environment for the sewage effluent of approximately 20% (13.6 million people) of the population of England, was observed to have the highest overall concentration of pharmaceuticals in contrast to the other estuaries sampled, thereby representing a worst case scenario for pharmaceutical pollution

    Anti-anxiety drugs and fish behavior: Establishing the link between internal concentrations of oxazepam and behavioral effects

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    This is the final published version. Available from Wiley via the DOI in this record.Some of the chemistry data have been provided in the Supplemental Data. The raw data from the behavioral analysis can be provided on contact with the corresponding author ([email protected]).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 (H T PC) 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 H T PC 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.Brunel University (London, UK)Spanish Ministry of Economy and CompetitivenessEconomy and Knowledge Department of the Catalan governmen

    Internal exposure dynamics drive the Adverse Outcome Pathways of synthetic glucocorticoids in fish

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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-species 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.This work was funded by a Biotechnology and Biological Sciences Research Council (BBSRC) Research Grant (BB/100646X/1), co-funded by the AstraZeneca Global Safety, Health and Environment research programme, to JPS and MR-W supporting LM-C
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