| 1. |
- Björlenius, Berndt, et al.
(author)
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Pharmaceutical residues are widespread in Baltic Sea coastal and offshore waters – Screening for pharmaceuticals and modelling of environmental concentrations of carbamazepine
- 2018
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In: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 633, s. 1496-1509
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Journal article (peer-reviewed)abstract
- The consumption of pharmaceuticals worldwide coupled with modest removal efficiencies of sewage treatment plants have resulted in the presence of pharmaceuticals in aquatic systems globally. In this study, we investigated the environmental concentrations of a selection of 93 pharmaceuticals in 43 locations in the Baltic Sea and Skagerrak. The Baltic Sea is vulnerable to anthropogenic activities due to a long turnover time and a sensitive ecosystem in the brackish water. Thirty-nine of 93 pharmaceuticals were detected in at least one sample, with concentrations ranging between 0.01 and 80 ng/L. One of the pharmaceuticals investigated, the anti-epileptic drug carbamazepine, was widespread in coastal and offshore seawaters (present in 37 of 43 samples). In order to predict concentrations of pharmaceuticals in the sub-basins of the Baltic Sea, a mass balance-based grey box model was set up and the persistent, widely used carbamazepine was selected as the model substance. The model was based on hydrological and meteorological sub-basin characteristics, removal data from smaller watersheds and wastewater treatment plants, and statistics relating to population, consumption and excretion rate of carbamazepine in humans. The grey box model predicted average environmental concentrations of carbamazepine in sub-basins with no significant difference from the measured concentrations, amounting to 0.57-3.2 ng/L depending on sub-basin location. In the Baltic Sea, the removal rate of carbamazepine in seawater was estimated to be 6.2 10(-9) s(-1) based on a calculated half-life time of 3.5 years at 10 degrees C, which demonstrates the long response time of the environment to measures phasing out persistent or slowly degradable substances such as carbamazepine. Sampling, analysis and grey box modelling were all valuable in describing the presence and removal of carbamazepine in the Baltic Sea.
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| 2. |
- Cerveny, D., et al.
(author)
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Neuroactive drugs and other pharmaceuticals found in blood plasma of wild European fish
- 2021
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In: Environmental International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 146
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Journal article (peer-reviewed)abstract
- To gain a better understanding of which pharmaceuticals could pose a risk to fish, 94 pharmaceuticals representing 23 classes were analyzed in blood plasma from wild bream, chub, and roach captured at 18 sites in Germany, the Czech Republic and the UK, respectively. Based on read across from humans, we evaluated the risks of pharmacological effects occurring in the fish for each measured pharmaceutical. Twenty-three compounds were found in fish plasma, with the highest levels measured in chub from the Czech Republic. None of the German bream had detectable levels of pharmaceuticals, whereas roach from the Thames had mostly low concentrations. For two pharmaceuticals, four individual Czech fish had plasma concentrations higher than the concentrations reached in the blood of human patients taking the corresponding medication. For nine additional compounds, determined concentrations exceeded 10% of the corresponding human therapeutic plasma concentration in 12 fish. The majority of the pharmaceuticals where a clear risk for pharmacological effects was identified targets the central nervous system. These include e.g. flupentixol, haloperidol, and risperidone, all of which have the potential to affect fish behavior. In addition to identifying pharmaceuticals of environmental concern, the results emphasize the value of environmental monitoring of internal drug levels in aquatic wildlife, as well as the need for more research to establish concentration-response relationships. © 2020 The Author(s)
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| 3. |
- Fick, Jerker, et al.
(author)
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Bioconcentration of Pharmaceuticals
- 2010. - 1
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In: Towards Sustainable Pharmaceuticals in a Healthy Society. - Stockholm : Elander Sverige AB. - 9789197883603 ; , s. 36-45
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Book chapter (other academic/artistic)abstract
- Residues of human pharmaceuticals have been widely detected in various parts of the environment and trace concentrations are often found in sewage effl uent and surface waters, typically ranging from low ng L-1 to low μg L-1 levels (Lindberg et al., 2005; Nikolaou et al., 2007; Loos et al., 2009). These concentrations, however, are orders of magnitude below the therapeutic concentrations reached in human blood plasma. Thus, the potential for a physiological impact of pharmaceuticals on water-living organisms (such as fi sh) have been questioned. On the other hand, the levels measured in surface waters do not simply mirror the levels encountered by the receptors or enzymes present inside the fi sh living in these waters. Indeed, levels of pharmaceutical in for example fi sh blood plasma is sometimes much higher than the levels in the surrounding water. This can be explained by the concepts of bioconcentration and bioaccumulation.
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| 4. |
- Fick, Jerker, et al.
(author)
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Contamination of surface, ground, and drinking water from pharmaceutical production
- 2009
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In: Environmental Toxicology and Chemistry. - : SETAC Journals. - 0730-7268 .- 1552-8618. ; 28:12, s. 2522-2527
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Journal article (peer-reviewed)abstract
- Low levels of pharmaceuticals are detected in surface, ground, and drinking water worldwide. Usage and incorrect disposal have been considered the major environmental sources of these micro-contaminants. Recent publications, however, suggest that wastewater from drug production can potentially be a source of much higher concentrations in certain locations. We investigated the environmental fate of active pharmaceutical ingredients in a major production area for the global bulk-drug market. Water samples were taken from a common effluent treatment plant near Hyderabad, India, which receives process water from about 90 bulk drug manufacturers. Surface water was analyzed from the recipient stream and from two lakes that are not contaminated by the treatment plant. Water samples were also taken from wells in six nearby villages. The samples were analyzed for the presence of twelve pharmaceuticals with LC-MS/MS. All wells were determined to be contaminated with drugs. Ciprofloxacin, enoxacin, cetirizine, terbinafine and citalopram were detected at >1microg l-1 in several wells. Very high concentrations of ciprofloxacin (up to 14 mg L-1) and other pharmaceuticals (up to 2 mg L-1) were found in the effluent of the treatment plant and in the two lakes (up to 6.5 mg L-1). Thus, insufficient wastewater treatment in one of the world's largest centers for bulk drug production leads to unprecedented drug contamination of surface, ground, and drinking water. This raises serious concerns regarding the development of antibiotic resistance, and it creates a major challenge for producers and regulatory agencies to improve the situation.
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| 5. |
- Fick, Jerker, et al.
(author)
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Predicted critical environmental concentrations for 500 pharmaceuticals
- 2010
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In: Regulatory toxicology and pharmacology. - : Elsevier. - 0273-2300 .- 1096-0295. ; 58:3, s. 516-23
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Journal article (peer-reviewed)abstract
- A growing number of pharmaceuticals are found in surface waters worldwide, raising concerns about their effects on aquatic organisms and it is a major challenge to develop a rational strategy for prioritizing drugs on which to focus the most extensive environmental research efforts. However, in contrast to most other chemicals, very good understanding of the human potency of pharmaceuticals has been obtained through efficacy and safety testing. Assuming that a drug acts primarily through the same target(s) also in a non-target species, it would be possible to predict the likelihood for pharmacological interactions in wildlife. Among aquatic organisms, fish most often share drug targets with humans. In this study, we have calculated the predicted critical environmental concentration (CECs), i.e. the surface water concentration expected to cause a pharmacological effect in fish, for 500 pharmaceuticals, assuming equivalent pharmacological activity. The CECs are based on literature data on human potencies together with a predicted bioconcentration factor in fish for each drug based on lipophilicity. We propose that CECs could be used as preliminary indicators of specific drugs' potential to cause adverse pharmacological effects at specific water concentrations, used when selecting pharmaceuticals to include in screening campaigns and for assessing relevant detection limits.
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| 6. |
- Fick, Jerker, et al.
(author)
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Therapeutic levels of levonorgestrel detected in blood plasma of fish: results from screening rainbow trout exposed to treated sewage effluents.
- 2010
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In: Environmental science & technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 44:7, s. 2661-2666
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Journal article (peer-reviewed)abstract
- Pharmaceuticals are found in surface waters worldwide, raising concerns about effects on aquatic organisms. Analyses of pharmaceuticals in blood plasma of fish could provide means to assess risk for pharmacological effects, as these concentrations could be compared with available human therapeutic plasma levels. In this study we investigated if fish exposed to sewage effluents have plasma concentrations of pharmaceuticals that are approaching human therapeutic levels. We also evaluated how well the bioconcentration of pharmaceuticals into fish blood plasma can be predicted based on lipophilicity. Rainbow trout were exposed to undiluted, treated sewage effluents at three sites in Sweden for 14 days. Levels of 25 pharmaceuticals in blood plasma and effluents were analyzed with liquid chromatography-mass spectrometry/mass spectrometry and gas chromatography-high resolution mass spectrometry. The progestin pharmaceutical levonorgestrel was detected in fish blood plasma at concentrations (8.5-12 ng mL(-1)), exceeding the human therapeutic plasma level. In total 16 pharmaceuticals were detected in fish plasma at concentrations higher than 1/1000 of the human therapeutic plasma concentration. Twenty-one pharmaceuticals were detected in either plasma or effluent, and 14 were detected in both compartments, allowing plasma bioconcentration factors to be determined. For 11 of these, theoretically calculated and experimentally measured values were in reasonably good agreement. However a few drugs, including levonorgestrel, did not bioconcentrate according to the screening model used. This study shows that rainbow trout exposed to sewage effluents have blood plasma levels of pharmaceuticals similar to human therapeutic concentrations, suggesting a risk for pharmacological effects in the fish. There is a particular concern about effects of progestin pharmaceuticals. For levonorgestrel, the measured effluent level (1 ng/L) was higher than water levels shown to reduce the fertility of fish.
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| 7. |
- Grabic, Roman, et al.
(author)
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Multi-residue method for trace level determination of pharmaceuticals in environmental samples using liquid chromatography coupled to triple quadrupole mass spectrometry
- 2012
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In: Talanta. - : Elsevier. - 0039-9140 .- 1873-3573. ; 100, s. 183-195
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Journal article (peer-reviewed)abstract
- A multi-residue method for the simultaneous determination of more than 90 pharmaceuticals in water samples was developed and validated. The developed method utilizes a single liquid chromatography–tandem mass spectrometry (LC–MS/MS) run after sample enrichment using solid-phase extraction (SPE). The pharmaceuticals included in this method were chosen based on their potency (effect/concentration ratio) and potential to bioaccumulate in fish. Because the selection was based on ecotoxicological criteria and not on ease of detection, the pharmaceuticals have a wide range of physico-chemical properties and represent twenty-seven distinct classes. No method for surface, waste water or similar matrices was previously described for 52 of the 100 target analytes. Four chromatographic columns were tested to optimize the separation prior to detection by mass spectrometry (MS). The resulting method utilizes a Hypersil Gold aQ column. Three different water matrices were tested during method validation: Milli-Q water, surface water (river water from the Umea River) and effluent from the Umea waste water treatment plant (WWTP). Four of the selected pharmaceuticals exhibited poor method efficiency in all matrices. Amiodarone, Dihydroergotamine, Perphenazine and Terbutalin were omitted from the final analytical method (). In addition, five compounds were excluded from the method for surface water (Atorvastatin, Chloropromazin, Dipyridamol, Furosemid and Ranitidin) and three other pharmaceuticals (Glibenclamid, Glimepirid and Meclozine) from waste water method respectively. Absolute recoveries were above 70% for Milli-Q water, surface water, and sewage effluent for most pharmaceuticals. The limits of quantification (LOQs) ranged from 0.05 to 50 ng L−1 (median 5 ng L−1). The use of matrix-matched standards led to the elimination of ionization enhancement or suppression. The recoveries of the method for real matrices were in the range of 23% to 134% for surface water (only three compounds were outside of the range of 40–130%) and in the range of 47% to 162% for waste water (five compounds were outside of the range of 40–130% at lower validated concentration).
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| 8. |
- Lindberg, Richard H, et al.
(author)
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Behavior of fluoroquinolones and trimethoprim during mechanical, chemical, and active sludge treatment of sewage water and digestion of sludge
- 2006
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In: Environmental Science and Technology. - Washington : American Chemical Society. - 0013-936X .- 1520-5851. ; 40:3, s. 1042-1048
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Journal article (peer-reviewed)abstract
- The behavior and fate of three fluoroquinolones (norfloxacin, ofloxacin, and ciprofloxacin), one sulfonamide (sulfamethoxazole), and trimethoprim were investigated at a sewage treatment plant in Umeå, Sweden, in 2004. This plant uses conventional mechanical, chemical, and activated sludge methods to treat the sewage water and digest the sludge; the dewatered digested sludge is pelleted (dry weight > 90% of total weight). Raw sewage water and particles as well as effluents and sludge from specific treatment areas within the plant were sampled. In addition to quantifying the antibiotics within the plant, we characterized the sample matrixes to facilitate evaluation of the results. Of the five substances examined, only norfloxacin, ciprofloxacin, and trimethoprim were present in concentrations higher than their limits of quantification. Norfloxacin and ciprofloxacin sorbed to sludge in a manner that was independent of changes in pH during sewage treatment, and more than 70% of the total amount of these compounds passing through the plant was ultimately found in the digested sludge. The results suggest that fluoroquinolones undergo thermal degradation during pelleting, but more studies are needed to confirm this. Trimethoprim was found in the final effluent at approximately the same concentration and mass flow as in the raw sewage, and could not be quantified in any solid sample. Predicted environmental concentrations, based on consumption data for Umeå municipality, correlated well with the results obtained, especially when the predicted concentrations were corrected to account for the amount of each active substance excreted in urine. The results obtained were compared to those of previous studies of these three substances' behavior and fate and were found to be similar, although some of the other plants studied employed the various treatment steps in different orders.
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| 9. |
- Lindberg, Richard H, et al.
(author)
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Occurrence and distribution of synthetic organic substances in boreal coniferous forest soils fertilized with hygienized municipal sewage sludge
- 2013
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In: Antibiotics. - : MDPI AG. - 2079-6382. ; 2:3, s. 352-366
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Journal article (peer-reviewed)abstract
- The occurrence and distribution of synthetic organic substances following application of dried and granulated (hygienized) municipal sewage sludge in Swedish boreal coniferous forests were investigated. Elevated concentrations of triclosan (TCS), polybrominated diphenyl ethers (PBDEs), and polychlorinated biphenyls (PCBs) were detected in the humus layer. Concentrations of ethinyl estradiol (EE2), norfloxacin, ciprofloxacin, ofloxacin (FQs), and polyaromatic hydrocarbons (PAHs) were not significantly influenced. Maximum concentrations in humus were as follows (in ng/g dry matter): TCS; 778; PBDEs; 25; and PCB7; 16.7. Fertilization did not alter the levels of the substances in mineral soil, ground water, and various types of samples related to air. Further research within this area is needed, including ecotoxicological effects and fate, in order to improve the knowledge regarding the use of sludge as a fertilizing agent. Continuous annual monitoring, with respect to sampling and analysis, should be conducted on the already-fertilized fields.
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| 10. |
- Lindberg, Richard H, et al.
(author)
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Screening of antimycotics in Swedish sewage treatment plants - Waters and sludge
- 2010
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In: Water Research. - : Elsevier Ltd. - 0043-1354 .- 1879-2448. ; 44:2, s. 649-57
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Journal article (peer-reviewed)abstract
- Concentrations of six pharmaceutical antimycotics were determined in the sewage water, final effluent and sludge of five Swedish sewage treatment plants (STPs) by solid phase extraction, liquid/solid extraction, and liquid chromatography-electrospray tandem mass spectrometry. The antimycotics were quantified by internal standard calibration. The results were used to estimate national flows that were compared to predictions based on sales figures. Fluconazole was the only one of the six investigated antimycotics that was detected (at concentrations ranging from 90 to 140ngL(-1)) in both raw sewage water and final effluent. Negligible amounts of this substance were removed from the aqueous phase, and its levels were below the limit of quantification in all of the analyzed sludge samples. In contrast, clotrimazole, ketoconazole and econazole were present in all of the sludge samples, at concentrations ranging between 200 and 1000mugkg(-1), dry weight. There were close correlations between the national measured and predicted antimycotic mass flows. Antimycotic fate analysis, based on sales figures, indicated that 53% of the total amount of fluconazole sold appeared in the final effluents of the STPs, while 1, 155, 35, 209 and 41% of the terbinafine, clotrimazole, ketoconazole, econazole and miconazole sold appeared in the digested dewatered sludge.
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