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- Cuklev, Filip, 1981, et al.
(författare)
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Diclofenac in fish : blood plasma levels similar to human therapeutic levels affect global hepatic gene expression
- 2011
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Ingår i: Environmental Toxicology and Chemistry. - New York : Pergamon. - 0730-7268 .- 1552-8618. ; 30:9, s. 2126-2134
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Tidskriftsartikel (refereegranskat)abstract
- Diclofenac is a non-steroidal anti-inflammatory drug frequently found in the aquatic environment. Previous studies have reported histological changes in the liver, kidney and gills of fish at concentrations similar to those measured in treated sewage effluents (approximately 1 µg/L). Analyses or predictions of blood plasma levels in fish allow a direct comparison with human therapeutic plasma levels, and may therefore be used to indicate a risk for pharmacological effects in fish. To relate internal exposure to a pharmacological interaction we investigated global hepatic gene expression together with bioconcentration in blood plasma and liver of rainbow trout (Oncorhynchus mykiss) exposed to waterborne diclofenac. At the highest exposure concentration (81.5 µg/L) the fish plasma concentration reached approximately 88% of the human therapeutic levels (C(max) ) after two weeks. Using an oligonucleotide microarray followed by quantitative PCR we found extensive effects on hepatic gene expression at this concentration, and some genes were found to be regulated down to the lowest concentration tested (1.6 µg/L) corresponding to approximately 1.5% of the human C(max) . Thus, at concentrations detected in European surface waters, diclofenac can affect the expression of multiple genes in exposed fish. Functional analysis of differentially expressed genes revealed effects on biological processes such as inflammation and immune response, in agreement with the mode of action of diclofenac in mammals. In contrast to some previously reported results, the bioconcentration factor was found to be stable (4.02 ± 0.75 for blood plasma and 2.54 ± 0.36 for liver) regardless of the water concentration. Environ. Toxicol. Chem. © 2011 SETAC.
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| 2. |
- Cuklev, Filip, 1981, et al.
(författare)
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Does ketoprofen or diclofenac pose the lowest risk to fish?
- 2012
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Ingår i: Journal of Hazardous Materials. - : Elsevier BV. - 0304-3894 .- 1873-3336. ; 229-230, s. 100-106
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Tidskriftsartikel (refereegranskat)abstract
- Ketoprofen and diclofenac are non-steroidal anti-inflammatory drugs (NSAIDs) often used for similar indications, and both are frequently found in surface waters. Diclofenac affects organ histology and gene expression in fish at around 1 mu g/L. Here, we exposed rainbow trout to ketoprofen (1, 10 and 100 mu g/L) to investigate if this alternative causes less risk for pharmacological responses in fish. The bioconcentration factor from water to fish blood plasma was <0.05(4 for diclofenac based on previous studies). Ketoprofen only reached up to 0.6 parts per thousand of the human therapeutic plasma concentration, thus the probability of target-related effects was estimated to be fairly low. Accordingly, a comprehensive analysis of hepatic gene expression revealed no consistent responses. In some contrast, trout exposed to undiluted, treated sewage effluents bioconcentrated ketoprofen and other NSAIDs much more efficiently, according to a meta-analysis of recent studies. Neither of the setups is however an ideal representation of the field situation. If a controlled exposure system with a single chemical in pure water is a reasonable representation of the environment, then the use of ketoprofen is likely to pose a lower risk for wild fish than diclofenac, but if bioconcentration factors from effluent-exposed fish are applied, the risks may be more similar.
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| 3. |
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| 4. |
- Gunnarsson, Lina-Maria, 1977, et al.
(författare)
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Pharmaceutical industry effluent diluted 1:500 affects global gene expression, cytochrome P4501A activity and plasma phosphate in fish
- 2009
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Ingår i: Environmental Toxicology and Chemistry. - : Society of Environmental Toxicology and Chemistry (SETAC). - 0730-7268 .- 1552-8618. ; 28:12, s. 2639-2647
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Tidskriftsartikel (refereegranskat)abstract
- Patancheru, near Hyderabad, India, is a major production site for the global bulk drug market. Approximately 90 manufacturers send their wastewater to a common treatment plant in Patancheru. Extraordinary high levels of a wide range of pharmaceuticals have recently been demonstrated in the treated effluent. As little as 0.2% of this effluent can strongly reduce the growth rate of tadpoles, but the underlying mechanisms of toxicity are not known. To begin addressing how the effluent affects aquatic vertebrates, rainbow trout (Oncorhynchus mykiss) were exposed to 0.2% effluent for five days. Several physiological endpoints, together with effects on global hepatic gene expression patterns, were analyzed. The exposed fish showed both an induction of hepatic cytochrome P450 1A (CYP1A) gene expression, as well as enzyme activity. Clinical blood chemistry analyses revealed an increase in plasma phosphate levels, which in humans indicates impaired kidney function. Several oxidative stress-related genes were induced in the livers; however, no significant changes in antioxidant enzyme activities or in the hepatic glutathione levels were found. Furthermore, estrogen-regulated genes were slightly up-regulated following exposure, and moderate levels of estriol were detected in the effluent. The present study identifies changes in gene expression triggered by exposure to a high dilution of the effluent, supporting the hypothesis that these fish are responding to chemical exposure. The pattern of regulated genes may contribute to the identification of mechanisms of sub-lethal toxicity, as well as illuminate possible causative agents.
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| 5. |
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| 6. |
- Holmberg, Anna, 1974, et al.
(författare)
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Does waterborne citalopram affect the aggressive and sexual behaviour of rainbow trout and guppy?
- 2011
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Ingår i: Journal of hazardous materials. - : Elsevier BV. - 1873-3336 .- 0304-3894. ; 187:1-3, s. 596-9
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Tidskriftsartikel (refereegranskat)abstract
- Citalopram is one of several selective serotonin reuptake inhibitors (SSRIs) commonly found in treated sewage effluents. Accordingly, there are concerns about possible adverse effects of SSRIs on aquatic organisms, particularly behavioural effects similar to those associated with SSRI use in humans. Rainbow trout fry and adult male guppies were therefore exposed to waterborne citalopram, ranging from environmentally relevant to high concentrations (1, 10, 100 μg/L) for 3-7 days. Under these experimental conditions citalopram does not appear to cause significant effects on aggression in rainbow trout fry or on sexual behaviour in male guppies. This may be explained by a relatively low uptake of citalopram from water to fish.
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| 7. |
- Larsson, D. G. Joakim, 1969, et al.
(författare)
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Release of active pharmaceutical ingredients from Indian bulk drug manufacture – environmental fate and effects on antibiotic resistance development, microbial ecosystems and vertebrate physiology
- 2008
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Ingår i: 2008 Society of Environmental Toxicology and Chemistry, November 16-20, Tampa, USA.
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Konferensbidrag (refereegranskat)abstract
- Last year, we published a paper showing extraordinary high levels of several drugs in treated effluent from a plant receiving process water from about 90 bulk drug manufacturers from the Hyderabad region in India. Particularly, the levels of various fluoroquinolones (up to 31 mg/L) called for more information on the potential development of antibiotic resistance of exposed bacteria, as well as potential ecological effects on microbial ecosystems. In this study we will present the first characterization of 93 strains of bacteria sampled inside the treatment facility for their sensitivity/resistance to 39 different antibiotics. Furthermore, controlled exposure experiments suggest that the treated effluent affects the functional structure of natural freshwater microbial communities at a dilution of 1:1000. Short to medium-term exposure experiments with frogs and fish demonstrate sublethal effects of the treated effluent at similar dilutions, suggesting that expected environmental effects are not restricted to disturbed microorganism communities. Data on the fate of different pharmaceuticals in a gradient up and downstream from the treatment facility will be presented, as well as levels in drinking water wells in seven nearby villages, showing a transport of drugs via the groundwater. We conclude that the environmental impact of drug production in the Hyderabad region is of great environmental concern. We will also present summary data on the origin of active substances present in pharmaceutical products on the Swedish market, implying an international responsibility for improving the environmental pollution situation related to bulk drug production in India.
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