| 1. |
- Cuklev, Filip, 1981, et al.
(författare)
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Global hepatic gene expression in rainbow trout exposed to sewage effluents: A comparison of different sewage treatment technologies
- 2012
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 427-428, s. 106-114
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Tidskriftsartikel (refereegranskat)abstract
- Effluents from sewage treatment plants contain a mixture of micropollutants with the potential of harming aquatic organisms. Thus, addition of advanced treatment techniques to complement existing conventional methods has been proposed. Some of the advanced techniques could, however, potentially produce additional compounds affecting exposed organisms by unknown modes of action. In the present study the aim was to improve our understanding of how exposure to different sewage effluents affects fish. This was achieved by explorative microarray and quantitative PCR analyses of hepatic gene expression, as well as relative organ sizes of rainbow trout exposed to different sewage effluents (conventionally treated, granular activated carbon, zonation (5 or 15 mg/L), 5 mg/L ozone plus a moving bed biofilm reactor, or UV-light treatment in combination with hydrogen peroxide). Exposure to the conventionally treated effluent caused a significant increase in liver and heart somatic indexes, an effect removed by all other treatments. Genes connected to xenobiotic metabolism, including cytochrome p450 1A, were differentially expressed in the fish exposed to the conventionally treated effluents, though only effluent treatment with granular activated carbon or ozone at 15 mg/L completely removed this response. The mRNA expression of heat shock protein 70 kDa was induced in all three groups exposed to ozone-treated effluents, suggesting some form of added stress in these fish. The induction of estrogen-responsive genes in the fish exposed to the conventionally treated effluent was effectively reduced by all investigated advanced treatment technologies, although the moving bed biofilm reactor was least efficient. Taken together, granular activated carbon showed the highest potential of reducing responses in fish induced by exposure to sewage effluents.
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| 2. |
- Wiklund, Daniel, et al.
(författare)
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Frictional mechanisms in mixed lubricated regime in steel sheet metal forming
- 2008
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Ingår i: Wear. - Amsterdam : Elsevier. - 0043-1648 .- 1873-2577. ; 264:5-6, s. 474-479
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Tidskriftsartikel (refereegranskat)abstract
- The friction is of critical importance to sheet metal forming operations. It affects the flow of material in the tool and thereby the scrap rate and final quality of products. In the experimental work the frictional response was measured in a bending under tension (BUT) test under mixed lubricated conditions. The study includes stainless steel, but previous research on carbon steels, coated and uncoated, are discussed also. The experimental results could be explained by the theory of pad bearings. The frictional response showed a correlation to the surface topography, e.g. the amplitude parameter (Sq) and texture aspect ratio parameter (Str). When predicting the frictional response of surfaces with multi-component distributions, the standard deviation of the distribution above the mean line could be used.
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| 3. |
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| 4. |
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| 5. |
- Albertsson, Eva, 1979, et al.
(författare)
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Proteomic analyses indicate induction of hepatic carbonyl reductase/20beta-hydroxysteroid dehydrogenase B in rainbow trout exposed to sewage effluent.
- 2007
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Ingår i: Ecotoxicology and environmental safety. - : Elsevier BV. - 0147-6513. ; 68:1, s. 33-9
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Tidskriftsartikel (refereegranskat)abstract
- Proteomic analyses were performed to identify regulated liver proteins in rainbow trout (Oncorhynchus mykiss) caged upstream and downstream from a sewage treatment works (STW). Two-dimensional gel electrophoresis, image analysis and FT-ICR mass-spectrometry revealed four regulated protein spots. The three down-regulated spots contained betaine aldehyde dehydrogenase, lactate dehydrogenase and an unidentified protein respectively. The only up-regulated spot consisted of both mitochondrial ATP synthase alpha-subunit and carbonyl reductase/20beta-hydroxysteroid dehydrogenase (CR/20beta-HSD). Further studies using quantitative PCR revealed a 13.5-fold induction of CR/20beta-HSD B mRNA following STW effluent exposure. The CR/20beta-HSD B gene was not regulated by 17alpha-ethinylestradiol, suggesting that its induction downstream from the STW is due to other factors than exposure to estrogens. Image analysis was initially performed on four gels from each group. These analyses suggested 15 regulated spots. However, validation of the 15 spots by increasing the number of replicates confirmed only four regulated spots. Hence, the present study also demonstrates the need for sufficient biological/technical replication in the interpretation of proteomic data.
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| 6. |
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| 7. |
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| 8. |
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| 9. |
- Bengtsson-Palme, Johan, 1985, et al.
(författare)
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Can branding and price of pharmaceuticals guide informed choices towards improved pollution control during manufacturing?
- 2018
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Ingår i: Journal of Cleaner Production. - 0959-6526. ; 171, s. 137-146
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Tidskriftsartikel (refereegranskat)abstract
- Pharmaceutical manufacturing can lead to substantial discharges of active pharmaceutical ingredients into the environment, with local consequences to the environment and, in the case of antibiotics, potentially global implications in terms of increasing risks for resistance development. In this study, we used Swedish sales data for pharmaceuticals combined with data on the origin of the active ingredients to determine if price pressure and generic substitution are related to the estimated general environmental performance and the perceived corruption levels of the production countries. In line with the general perception, India was the largest producer of generics, while Europe and the USA dominated for branded products. We found that the price and environmental performance index of the production countries were linked, but that this relationship was largely explained by whether the product was original or generic. Although this relationship would allow buyers to select products that are more likely to originate from countries that, in general terms, have better pollution control, it lacks resolution. We conclude that to better allow consumers, hospitals and pharmacies to influence the environmental impact of their product choices, there is need for regulation as well as transparency in the production chain. To this end, emissions from manufacturing need to be measured, allowing for control and follow-up on industry commitments towards sustainable manufacturing of pharmaceuticals.
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| 10. |
- Bylander, Anna, 1979, et al.
(författare)
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Progesterone-mediated effects on gene expression and oocyte-cumulus complex transport in the mouse fallopian tube.
- 2015
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Ingår i: Reproductive biology and endocrinology : RB&E. - : Springer Science and Business Media LLC. - 1477-7827. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- The fallopian tube transports the gametes to the fertilization site and delivers the embryo to the uterus at the optimal time for implantation. Progesterone and the classical progesterone receptor are involved in regulating both tubal ciliary beating and muscular contractions, likely via both genomic and non-genomic actions.
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| 11. |
- Carney Almroth, Bethanie, 1974, et al.
(författare)
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Waterborne beclomethasone dipropionate affects the physiology of fish while its metabolite beclomethasone is not taken up
- 2015
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 511, s. 37-46
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Tidskriftsartikel (refereegranskat)abstract
- Asthma is commonly treated with inhalable glucocorticosteroids, including beclomethasone dipropionate (BDP). This is a synthetic prodrug which is metabolized to the more active monopropionate (BMP) and free beclomethasone in humans. To evaluate potential effects of residual drugs on fish, we conducted a 14 day flow-through exposure experiment with BDP and beclomethasone using rainbow trout, and analyzed effects on plasma glucose, hepatic glutathione and catalase activity together with water and body concentrations of the BDP, BMP and beclomethasone. We also analyzed hepatic gene expression in BDP-exposed fish by microarray and quantitative PCR. Beclomethasone (up to 0.65 μg/L) was not taken up in the fish while BDP (0.65 and 0.07 μg/L) resulted in accumulation of both beclomethasone, BMP and BDP in plasma, reaching levels up to those found in humans during therapy. Accordingly, exposure to 0.65 μg/L of BDP significantly increased blood glucose as well as oxidized glutathione levels and catalase activity in the liver. Exposure to beclomethasone or the low concentration of BDP had no effect on these endpoints. Both exposure concentrations of BDP resulted in significantly higher transcript abundance of phosphoenolpyruvate carboxykinase involved in gluconeogenesis, and of genes involved in immune responses. As only the rapidly metabolized prodrug was potent in fish, the environmental risks associated with the use of BDP are probably small. However, the observed physiological effects in fish of BDP at plasma concentrations known to affect human physiology provides valuable input to the development of read-across approaches in the identification of pharmaceuticals of environmental concern.
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| 12. |
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| 13. |
- Gunnarsson, Lina-Maria, 1977, et al.
(författare)
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Comparison of six different sewage treatment processes-Reduction of estrogenic substances and effects on gene expression in exposed male fish
- 2009
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Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 407:19, s. 5235-5242
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Tidskriftsartikel (refereegranskat)abstract
- Treated sewage effluents often contain a mixture of estrogenic compounds in low concentrations. The total combined activity of these, however, may be sufficiently high to affect the reproduction of aquatic vertebrates. The introduction of advanced treatment technologies has been suggested as a way to remove micro-contaminants, including estrogenic substances. In this study, one municipal influent was treated with six different processes in parallel on a semi-large scale in order to assess their potential to reduce substances that could contribute to estrogenic effects in male fish. The effluent from a conventional, activated sludge treatment line was compared to a similarly treated effluent with a final sand-filtering step. The addition of ozonation (15 g O-3/m(3)). a moving bed biofilm reactor (MBBR) or both in combination was also evaluated. There was also a separate treatment line that was based on a membrane bioreactor. A small battery of hepatic estrogen-responsive genes was measured in the exposed fish using quantitative PCR. Concentrations of steroid estrogens and estrogenic phenols in the effluents were measured by GC-ECNI-MS. The ozonated effluents were the only tested effluents for which all measured biological effects in exposed fish were removed. Chemical data suggested that the MBBR technology was equally effective in removing the analyzed estrogens; however, elevated expression of estrogen-responsive genes suggested that some estrogenic substances were still present in the effluent. The membrane bioreactor removed most of the measured estrogens and it reduced the induction of the estrogen-responsive genes. However, fish exposed to this effluent had significantly enlarged livers. Given that the same influent was treated in parallel with a broad set of technologies and that the chemical analyses were combined with an in vivo assessment of estrogenic responses, this study provides valuable input into the assessment of advanced treatment processes for removing estrogenic substances.
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| 14. |
- Gunnarsson, Lina-Maria, 1977, et al.
(författare)
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Evolutionary conservation of human drug targets in organisms used for environmental risk assessments.
- 2008
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Ingår i: Environmental science & technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 42:15, s. 5807-13
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Tidskriftsartikel (refereegranskat)abstract
- Pharmaceuticals are typically found in very low concentrations in the aquatic environment. Accordingly, environmental effects clearly assigned to residual drugs are consistent with high affinity interactions with conserved targets in affected wildlife species rather than with a general toxic effect. Thus, evolutionarily well-conserved targets in a given species are associated with an increased risk. In this study orthologs for 1318 human drug targets were predicted in 16 species of which several are relevant for ecotoxicity testing. The conservation of different functional categories of targets was also analyzed. Zebrafish had orthologs to 86% of the drug targets while only 61% were conserved in Daphnia and 35% in green alga. The predicted presence and absence of orthologs agrees well with published experimental data on the potential for specific drug target interaction in various species. Based on the conservation of targets we propose that aquatic environmental risk assessments for human drugs should always include comprehensive studies on aquatic vertebrates. Furthermore, individual targets, especially enzymes, are well conserved suggesting that tests on evolutionarily distant organisms would be highly relevant for certain drugs. We propose that the results can guide environmental risk assessments by improving the possibilities to identify species sensitive to certain types of pharmaceuticals or to other contaminants that act through well defined mechanisms of action. Moreover, we suggest that the results can be used to interpret the relevance of existing ecotoxicity data.
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| 15. |
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| 16. |
- Gunnarsson, Lina-Maria, 1977
(författare)
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On the use of genomics to asses environmental risks of pharmaceuticals
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Many drugs are found in the aquatic environment and are therefore a cause for concern. Low concentrations of active ingredients from human pharmaceuticals reach the environment via sewage treatment plants, mainly as a result of excretion. However, other routes, such as incorrect disposal and direct releases from manufacture, could also be of importance. The effects of residual drugs in the environment are not well understood. This thesis addresses the issue by using different genomic techniques. The evolutionary conservation of 1,318 human drug targets were predicted in 16 species from different taxonomic groups. We show that the majority of the drug targets are conserved in aquatic vertebrates, while invertebrates and plants lack orthologs to many of the targets. The presented predictions can serve as a basis for identifying potentially sensitive (and insensitive) species that are used for the environmental risk assessment of pharmaceuticals. The effects on fish of exposure to a single pharmaceutical (ethinylestradiol) as well as a complex industrial effluent that contains high levels of many drugs were explored using microarray analysis. We identified two sensitive and potentially robust biomarkers of estrogen exposure by performing a meta-analysis that combined our results with data from the literature. The identified biomarkers were also used to evaluate the ability of different sewage treatment technologies to remove estrogenic substances. Several treatment technologies reduced the levels of estrogenic substances, but ozonation was required to remove all measured biological effects. The fish that were exposed to a high dilution of the industrial effluent showed increased hepatic Cyp1a enzyme activity and altered expression of several genes that are involved in the detoxification of chemicals and drugs. Although the gene expression pattern did not clearly point to any specific group of substances, it could serve as a basis for hypothesizing mechanisms of toxicity and possible causative agents in the effluent. More research is needed to understand the risks of residual drugs in the environment, and the presented results show that genomic approaches are useful for this purpose.
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| 17. |
- 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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| 18. |
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| 19. |
- Gunnarsson, Lina-Maria, 1977, et al.
(författare)
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Sensitive and robust gene expression changes in fish exposed to estrogen – a microarray approach
- 2007
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Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 8:149
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Tidskriftsartikel (refereegranskat)abstract
- Background Vitellogenin is a well established biomarker for estrogenic exposure in fish. However, effects on gonadal differentiation at concentrations of estrogen not sufficient to give rise to a measurable vitellogenin response suggest that more sensitive biomarkers would be useful. Induction of zona pellucida genes may be more sensitive but their specificities are not as clear. The objective of this study was to find additional sensitive and robust candidate biomarkers of estrogenic exposure. Results Hepatic mRNA expression profiles were characterized in juvenile rainbow trout exposed to a measured concentration of 0.87 and 10 ng ethinylestradiol/L using a salmonid cDNA microarray. The higher concentration was used to guide the subsequent identification of generally more subtle responses at the low concentration not sufficient to induce vitellogenin. A meta-analysis was performed with data from the present study and three similar microarray studies using different fish species and platforms. Within the generated list of presumably robust responses, several well-known estrogen-regulated genes were identified. Two genes, confirmed by quantitative RT-PCR (qPCR), fulfilled both the criteria of high sensitivity and robustness; the induction of the genes encoding zona pellucida protein 3 and a nucleoside diphosphate kinase (nm23). Conclusion The cross-species, cross-platform meta-analysis correctly identified several robust responses. This adds confidence to our approach used for identifying candidate biomarkers. Specifically, we propose that analyses of an nm23 gene together with zona pellucida genes may increase the possibilities to detect an exposure to low levels of estrogenic compounds in fish.
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| 20. |
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| 21. |
- Kristiansson, Erik, 1978, et al.
(författare)
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A novel method for cross-species gene expression analysis
- 2013
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Ingår i: BMC Bioinformatics. - : Springer Science and Business Media LLC. - 1471-2105. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background Analysis of gene expression from different species is a powerful way to identify evolutionarily conserved transcriptional responses. However, due to evolutionary events such as gene duplication, there is no one-to-one correspondence between genes from different species which makes comparison of their expression profiles complex. Results In this paper we describe a new method for cross-species meta-analysis of gene expression. The method takes the homology structure between compared species into account and can therefore compare expression data from genes with any number of orthologs and paralogs. A simulation study shows that the proposed method results in a substantial increase in statistical power compared to previously suggested procedures. As a proof of concept, we analyzed microarray data from heat stress experiments performed in eight species and identified several well-known evolutionarily conserved transcriptional responses. The method was also applied to gene expression profiles from five studies of estrogen exposed fish and both known and potentially novel responses were identified. Conclusions The method described in this paper will further increase the potential and reliability of meta-analysis of gene expression profiles from evolutionarily distant species. The method has been implemented in R and is freely available at http://bioinformatics.math.chalmers.se/Xspecies/ webcite.
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| 22. |
- Kristiansson, Erik, 1978, et al.
(författare)
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Does the scientific knowledge reflect the chemical diversity of environmental pollution? – A twenty-year perspective
- 2021
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Ingår i: Environmental Science and Policy. - : Elsevier BV. - 1873-6416 .- 1462-9011. ; 126, s. 90-98
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Tidskriftsartikel (refereegranskat)abstract
- Environmental policymaking relies heavily on the knowledge of the toxicological properties of chemical pollutants. The ecotoxicological research community is an important contributor to this knowledge, which together with data from standardized tests supports policy-makers in taking the decisions required to reach an appropriate level of protection of the environment. The chemosphere is, however, massive and contains thousands of chemicals that can constitute a risk if present in the environment at sufficiently high concentrations. The scientific ecotoxicological knowledge is growing but it is not clear to what extent the research community manages to cover the large chemical diversity of environmental pollution. In this study, we aimed to provide an overview of the scientific knowledge generated within the field of ecotoxicology during the last twenty years. By using text mining of over 130,000 scientific papers we established time-trends describing the yearly publication frequency of over 3500 chemicals. Our results show that ecotoxicological research is highly focused and that as few as 65 chemicals corresponded to half of all occurrences in the scientific literature. We, furthermore, demonstrate that the last decades have seen substantial changes in research direction, where the interest in pharmaceuticals has grown while the interest in biocides has declined. Several individual chemicals showed an especially rapid increase (e.g. ciprofloxacin, diclofenac) or decrease (e.g. lindane and atrazine) in occurrence in the literature. We also show that university- and corporate-based research exhibit distinct publication patterns and that for some chemicals the scientific knowledge is dominated by publications associated with the industry. This study paints a unique picture and provides quantitative estimates of the scientific knowledge of environmental chemical pollution generated during the last two decades. We conclude that there is a large number of chemicals with little, or no, scientific knowledge and that a continued expansion of the field of ecotoxicology will be necessary to catch up with the constantly increasing diversity of chemicals used within the society.
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| 23. |
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| 24. |
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| 25. |
- 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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| 26. |
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| 27. |
- Lind, Ulrika, et al.
(författare)
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Octopamine receptors from the barnacle balanus improvisus are activated by the alpha2-adrenoceptor agonist medetomidine.
- 2010
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Ingår i: Molecular pharmacology. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 1521-0111 .- 0026-895X. ; 78:2, s. 237-48
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Tidskriftsartikel (refereegranskat)abstract
- G protein-coupled octopamine receptors of insects and other invertebrates represent counterparts of adrenoceptors in vertebrate animals. The alpha(2)-adrenoceptor agonist medetomidine, which is in clinical use as a veterinary sedative agent, was discovered to inhibit the settling process of barnacles, an important step in the ontogeny of this crustacean species. Settling of barnacles onto ship hulls leads to biofouling that has many harmful practical consequences, and medetomidine is currently under development as a novel type of antifouling agent. We now report that medetomidine induces hyperactivity in the barnacle larvae to disrupt the settling process. To identify the molecular targets of medetomidine, we cloned five octopamine receptors from the barnacle Balanus improvisus. We show by phylogenetic analyses that one receptor (BiOctalpha) belongs to the alpha-adrenoceptor-like subfamily, and the other four (BiOctbeta-R1, BiOctbeta-R2, BiOctbeta-R3, and BiOctbeta-R4) belong to the beta-adrenoceptor-like octopamine receptor subfamily. Phylogenetic analyses also indicated that B. improvisus has a different repertoire of beta-adrenoceptor-like octopamine receptors than insects. When expressed in CHO cells, the cloned receptors were activated by both octopamine and medetomidine, resulting in increased intracellular cAMP or calcium levels. Tyramine activated the receptors but with much lesser potency than octopamine. A hypothesis for receptor discrimination between tyramine and octopamine was generated from a homology three-dimensional model. The characterization of B. improvisus octopamine receptors is important for a better functional understanding of these receptors in crustaceans as well as for practical applications in development of environmentally sustainable antifouling agents.
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| 28. |
- Roos, Vendela, et al.
(författare)
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Prioritising pharmaceuticals for environmental risk assessment: Towards adequate and feasible first-tier selection.
- 2012
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Ingår i: The Science of the total environment. - Amsterdam : Elsevier BV. - 1879-1026 .- 0048-9697. ; 421-422, s. 102-10
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Tidskriftsartikel (refereegranskat)abstract
- The presence of pharmaceuticals in the aquatic environment, and the concerns for negative effects on aquatic organisms, has gained increasing attention over the last years. As ecotoxicity data are lacking for most active pharmaceutical ingredients (APIs), it is important to identify strategies to prioritise APIs for ecotoxicity testing and environmental monitoring. We have used nine previously proposed prioritisation schemes, both risk- and hazard-based, to rank 582 APIs. The similarities and differences in overall ranking results and input data were compared. Moreover, we analysed how well the methods ranked seven relatively well-studied APIs. It is concluded that the hazard-based methods were more successful in correctly ranking the well-studied APIs, but the fish plasma model, which includes human pharmacological data, also showed a high success rate. The results of the analyses show that the input data availability vary significantly; some data, such as logP, are available for most API while information about environmental concentrations and bioconcentration are still scarce. The results also suggest that the exposure estimates in risk-based methods need to be improved and that the inclusion of effect measures at first-tier prioritisation might underestimate risks. It is proposed that in order to develop an adequate prioritisation scheme, improved data on exposure such as degradation and sewage treatment removal and bioconcentration ability should be further considered. The use of ATC codes may also be useful for the development of a prioritisation scheme that includes the mode of action of pharmaceuticals and, to some extent, mixture effects.
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| 29. |
- Rutgersson, Carolin, 1983, et al.
(författare)
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Oral exposure to industrial effluent with exceptionally high levels of drugs does not indicate acute toxic effects in rats
- 2013
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Ingår i: Environmental Toxicology and Chemistry. - : Wiley. - 0730-7268 .- 1552-8618. ; 32:3, s. 577-584
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Tidskriftsartikel (refereegranskat)abstract
- The Patancheru area near Hyderabad in India is recognized as a key link in the global supply chain for many bulk drugs. A central treatment plant receives wastewater from approximately 90 different manufacturers, and the resulting complex effluent has contaminated surface, ground, and drinking water in the region. Ecotoxicological testing of the effluent has shown adverse effects for several organisms, including aquatic vertebrates, at high dilutions. In addition, a recent study of microbial communities in river sediment indicated that the contamination of antibiotic substances might contribute to the emergence and spread of antibiotic resistance genes. In an attempt to start investigating how exposure to effluent-contaminated water may directly affect humans and other terrestrial vertebrates, rats were tube-fed effluent. Several pharmaceuticals present in the effluent could be detected in rat blood serum at low concentrations. However, results from exploratory microarray and quantitative polymerase chain reaction assays indicated no marked effects on hepatic gene transcription after 5 d of exposure. Neither did clinical analysis of blood serum constituents, used as biomarkers for human disease, reveal any significant changes, nor was there any weight gain. Taken together, the authors could not find evidence for any acute toxicity in the rat; however, the authors cannot rule out that higher doses of effluent or a longer exposure time may still be associated with risks for terrestrial vertebrates.
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| 30. |
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| 32. |
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