| 1. |
- Gustafsson, Kerstin, et al.
(författare)
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Direct and indirect effects of the fungicide azoxystrobin in outdoor brackish water microcosms
- 2010
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Ingår i: Ecotoxicology. - : Springer Science and Business Media LLC. - 0963-9292 .- 1573-3017. ; 19:2, s. 431-444
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Tidskriftsartikel (refereegranskat)abstract
- The effects of the strobilurin fungicide azoxystrobin were studied in brackish water microcosms, with natural plankton communities and sediment. Two experiments were conducted: Experiment 1 (nominal conc. 0, 15 and 60 mu g/L, 24-L outdoor microcosms for 21 days) and a second, follow-up, Experiment 2 (nominal conc. 0, 3, 7.5, 15 mu g/L, 4-L indoor microcosms for 12 days). The microcosms represent a simplified brackish water community found in shallow semi-enclosed coastal areas in agricultural districts in the Baltic Sea region. Measured water concentrations of the fungicide (Experiment 1) were, on average, 83 and 62% of nominal concentrations directly after application, and 25 and 30% after 21 days, for the low and high dose treatments, respectively, corresponding to mean DT50-values of 15.1 and 25.8 days, for low and high dose treatments, respectively. In Experiment 1, direct toxic effects on calanoid copepods at both test concentrations were observed. Similarly, in Experiment 2, the copepod abundance was significantly reduced at all tested concentrations. There were also significant secondary effects on zooplankton and phytoplankton community structure, standing stocks and primary production. Very few ecotoxicological studies have investigated effects of plant protection products on Baltic organisms in general and effects on community structure and function specifically. Our results show that azoxystrobin is toxic to brackish water copepods at considerably lower concentrations than previously reported from single species tests on freshwater crustaceans, and that direct toxic effects on this ecologically important group may lead to cascade effects altering lower food webs and ecosystem functioning.
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| 2. |
- Nilsson, Mats F., et al.
(författare)
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Improved methodology for identifying the teratogenic potential in early drug development of hERG channel blocking drugs
- 2010
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Ingår i: Reproductive Toxicology. - : Elsevier. - 0890-6238 .- 1873-1708. ; 29:2, s. 156-163
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Tidskriftsartikel (refereegranskat)abstract
- Drugs blocking the potassium current IKr of the heart (via hERG channel-inhibition) have the potential to cause hypoxia-related teratogenic effects. However, this activity may be missed in conventional teratology studies because repeat dosing may cause resorptions. The aim of the present study was to investigate an alternative protocol to reveal the teratogenic potential of IKr-blocking drugs. The IKr blocker astemizole, given as a single dose (80mg/kg) on gestation day (GD) 13 to pregnant rats caused digital defects. In whole rat embryo culture (2h) on GD 13, astemizole caused a decrease in embryonic heart rate at 20nM, and arrhythmias at 200-400nM. Cetirizine, without IKr-blocking properties, did not affect the rat embryonic heart in vitro. The present study shows that single dose testing on sensitive days of development, together with whole embryo culture, can be a useful methodology to better characterize the teratogenic potential of IKr-blocking drugs.
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| 3. |
- Gillman, Anna, et al.
(författare)
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Oseltamivir-Resistant Influenza A (H1N1) Virus Strain with an H274Y Mutation in Neuraminidase Persists without Drug Pressure in Infected Mallards
- 2015
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Ingår i: Applied and Environmental Microbiology. - : American Society for Microbiology. - 0099-2240 .- 1098-5336. ; 81:7, s. 2378-2383
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Tidskriftsartikel (refereegranskat)abstract
- Influenza A virus (IAV) has its natural reservoir in wild waterfowl, and emerging human IAVs often contain gene segments from avian viruses. The active drug metabolite of oseltamivir (oseltamivir carboxylate [OC]), stockpiled as Tamiflu for influenza pandemic preparedness, is not removed by conventional sewage treatment and has been detected in river water. There, it may exert evolutionary pressure on avian IAV in waterfowl, resulting in the development of resistant viral variants. A resistant avian IAV can circulate among wild birds only if resistance does not restrict viral fitness and if the resistant virus can persist without continuous drug pressure. In this in vivo mallard (Anas platyrhynchos) study, we tested whether an OC-resistant avian IAV (H1N1) strain with an H274Y mutation in the neuraminidase (NA-H274Y) could retain resistance while drug pressure was gradually removed. Successively infected mallards were exposed to decreasing levels of OC, and fecal samples were analyzed for the neuraminidase sequence and phenotypic resistance. No reversion to wild-type virus was observed during the experiment, which included 17 days of viral transmission among 10 ducks exposed to OC concentrations below resistance induction levels. We conclude that resistance in avian IAV that is induced by exposure of the natural host to OC can persist in the absence of the drug. Thus, there is a risk that human-pathogenic IAVs that evolve from IAVs circulating among wild birds may contain resistance mutations. An oseltamivir-resistant pandemic IAV would pose a substantial public health threat. Therefore, our observations underscore the need for prudent oseltamivir use, upgraded sewage treatment, and surveillance for resistant IAVs in wild birds.
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| 4. |
- Leffler, Per, et al.
(författare)
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Toxicity and accumulation of trinitrotoluene (TNT) and its metabolites in atlantic salmon alevins exposed to an industrially polluted water
- 2014
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Ingår i: Journal of Toxicology and Environmental Health. - : Taylor & Francis Group. - 1528-7394 .- 1087-2620. ; 77:19, s. 1183-1191
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Tidskriftsartikel (refereegranskat)abstract
- A pond in an industrial area in Sweden was selected to study adverse effects on salmon alevins from 2,4,6-trinitrotoluene (TNT)-contaminated water. Chemical screening revealed heavy contamination of TNT and its degradation products, 2-amino-4,6-dinitrotoluene (2-ADNT) and 4-amino-2,6-dinitrotoluene (4-ADNT), ranging from 0.05 to 230 g/kg in the sediment (dry weight) within the water system. Pond water contained 3 mg/L TNT. A dilution series of pond water mixed with tap water revealed increased death frequency in alevins down to fivefold dilution (approximate 0.4 mg TNT/L). Uptake was concentration dependent, reaching 7, 9, and 22 μg/g tissue for TNT, 2-ADNT, and 4-ADNT at the highest test concentration. A time-dependent uptake of TNT and its degradation products was found at a water concentration of 0.08 mg TNT/L. Degradation products of TNT showed a more efficient uptake compared to native TNT, and accumulation of 4-ADNT was more pronounced during the late phase of the 40-d exposure study. Bioconcentration factors (BCF) (0.34, 52, and 134 ml/g for TNT, 2-ADNT, and 4-ADNT, respectively) demonstrated a significant uptake of the metabolite 4-ADNT in alevin tissue. Disturbed physiological conditions and delayed development in alevins were not studied, but may not be excluded even at 125-fold diluted pond water (0.016 mg TNT/L). BCF data indicated that bioaccumulation of TNT metabolites need to be considered in TNT chronic toxicity. Fish species and age differences in the accumulation of TNT metabolites need to be further studied.
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| 5. |
- Mwevura, Haji, et al.
(författare)
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Organohalogen compounds in blubber of Indo-Pacific bottlenose dolphin (Tursiops aduncus) and spinner dolphin (Stenella longirostris) from Zanzibar, Tanzania
- 2010
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Ingår i: Environmental Pollution. - : Elsevier BV. - 0269-7491 .- 1873-6424. ; 158:6, s. 2200-2207
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Tidskriftsartikel (refereegranskat)abstract
- Blubber samples of Indo-Pacific bottlenose (Tursiops aduncus) and spinner (Stenella longirostris) dolphins from Zanzibar, East Africa, were analysed for a wide range of organohalogen compounds. Methoxylated polybrominated diphenyl ethers (MeO-BDEs), presumably biogenic, were found at higher concentrations than anthropogenic organochlorine pesticides (OCPs). Only traces of industrial pollutants, such as polychlorinated biphenyls, were detected. The OCP levels found off Zanzibar were lower than those reported from other regions while MeO-BDE levels were higher. The relative composition of the OCPs indicated recent use of lindane (γ-hexachlorocyclohexane) and aged residues of DDT and technical HCH. Placental transfer was estimated to 2.5% and 0.5% of the total burden of OCPs and MeO-BDEs, respectively. Overall transfer from mother to calf in Indo-Pacific bottlenose dolphins was estimated to 72% and 85% for the OCPs and MeO-BDEs burdens, respectively. Health effects of MeO-BDEs are not known, but structural similarities with well-known environmental toxins are cause for concern.
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| 6. |
- Held, Felix, et al.
(författare)
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Modelling of oscillatory cortisol response in horses using a Bayesian population approach for evaluation of dexamethasone suppression test protocols
- 2019
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Ingår i: Journal of Pharmacokinetics and Pharmacodynamics. - : Springer Science and Business Media LLC. - 1567-567X .- 1573-8744. ; 46:1, s. 75-87
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Tidskriftsartikel (refereegranskat)abstract
- Cortisol is a steroid hormone relevant to immune function in horses and other species and shows a circadian rhythm. The glucocorticoid dexamethasone suppresses cortisol in horses. Pituitary pars intermedia dysfunction (PPID) is a disease in which the cortisol suppression mechanism through dexamethasone is challenged. Overnight dexamethasone suppression test (DST) protocols are used to test the functioning of this mechanism and to establish a diagnosis for PPID. However, existing DST protocols have been recognized to perform poorly in previous experimental studies, often indicating presence of PPID in healthy horses. This study uses a pharmacokinetic/pharmacodynamic (PK/PD) modelling approach to analyse the oscillatory cortisol response and its interaction with dexamethasone. Two existing DST protocols were then scrutinized using model simulations with particular focus on their ability to avoid false positive outcomes. Using a Bayesian population approach allowed for quantification of uncertainty and enabled predictions for a broader population of horses than the underlying sample. Dose selection and sampling time point were both determined to have large influence on the number of false positives. Advice on pitfalls in test protocols and directions for possible improvement of DST protocols were given. The presented methodology is also easily extended to other clinical test protocols.
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| 7. |
- Näslund, Johanna, et al.
(författare)
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Diclofenac affects kidney histology in the three-spined stickleback (Gasterosteus aculeatus) at low mu g/L concentrations
- 2017
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Ingår i: Aquatic Toxicology. - : Elsevier BV. - 0166-445X .- 1879-1514. ; 189, s. 87-96
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Tidskriftsartikel (refereegranskat)abstract
- Diclofenac, a commonly used non-steroidal anti-inflammatory drug, is considered for regulation under the European water framework directive. This is because effects on fish have been reported at concentrations around those regularly found in treated sewage effluents (similar to 1 mu g/L). However, a recent publication reports no effects on fish at 320 mu g/L. In this study, three-spined sticklebacks (Gasterosteus aculeatus) were exposed to 0, 4.6, 22, 82 and 271 mu g/L diclofenac in flow-through systems for 28 days using triplicate aquaria per concentration. At the highest concentration, significant mortalities were observed already after 21 days (no mortalities found up to 22 mu g/L). Histological analysis revealed a significant increase in the proportion of renal hematopoietic tissue (renal hematopoietic hyperplasia) after 28 days at the lowest concentration and at all higher concentrations, following a clear dose-response pattern. Skin ulcerations of the jaw were noted by macroscopic observations, primarily at the two highest concentrations. No histological changes were observed in the liver. There was an increase in the relative hepatic mRNA levels of c7 (complement component 7), a gene involved in the innate immune system, at 22 mu g/L and at all higher concentrations, again following a clear dose-response. The bio-concentration factor was stable across concentrations, but lower than reported for rainbow trout, suggesting lower internal exposure to the drug in the stickleback. In conclusion, this study demonstrates that diclofenac causes histological changes in the three-spined stickleback at low mu g/L concentrations, which cause concern for fish populations exposed to treated sewage effluents.
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| 8. |
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| 9. |
- Nyström, Jennifer, et al.
(författare)
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Healthy eating index and diet diversity score as determinants of serum perfluoroalkyl acid (PFAA) concentrations in a national survey of Swedish adolescents
- 2022
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Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 212, Part A
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Tidskriftsartikel (refereegranskat)abstract
- Food is an important source of perfluoroalkyl acid (PFAA) exposure for the general adult population, but few data exist for adolescents. Healthy food habits established during adolescence may positively influence health later in life. Associations between serum PFAA concentrations and a healthy eating index (SHEIA15), as well as a diet diversity score (RADDS), were determined in a nationally representative adolescent population from Sweden (Riksmaten Adolescents 2016–2017, RMA). Using consumption data from food registrations and frequency questionnaires, we additionally analyzed associations with commonly consumed food groups. Associations were analyzed by fitting a cumulative probability model using ordinal regression. Among the seven PFAAs detected in ≥70% of the 1098 participants (age 10–21 years), median concentrations ranged from <1 ng/g serum of perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perflurorundecanoic acid (PFUnDA), linear (lin-) perfluorohexanesulfonic acid (PFHxS) and branched (br-) perfluorooctanesulfonic acid (PFOS) to 1–2 ng/g serum of lin-perfluorooctanoic acid (PFOA) and lin-PFOS. PFNA, PFDA, PFUnDA and lin-PFOS concentrations were positively associated with both SHEIA15 and RADDS, a finding most likely driven by higher consumption of seafood. PFDA, PFUnDA and lin-PFOS concentrations were positively related to commonly consumed fish/shellfish groups, such as lean marine fish and shellfish. Inverse associations between PFAA concentrations and dairy consumption suggest an underlying factor behind dairy consumption that similarly affects adolescent exposure to the different PFAAs. Isomeric differences in dietary exposure between lin-PFOS and br-PFOS were suggested, as br-PFOS concentrations, in contrast to lin-PFOS, were not associated with SHEIA15, RADDS and consumption of different food groups. We conclude that Swedish adolescents, adhering to a diverse and healthy diet, appears to be more highly exposed to legacy PFAAs than those eating less healthy. Additional research is necessary for a better understanding of the health implications of healthy eating from a PFAA exposure perspective.
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| 10. |
- Villén, Johanna, et al.
(författare)
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Estimating environmental exposure to analgesic drugs : A cross-sectional study of drug utilization patterns in the area surrounding Sweden's largest drinking water source
- 2023
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Ingår i: Environmental Advances. - : Elsevier. - 2666-7657. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Use of pharmaceuticals is continuously increasing globally and their residues are recognized as a risk for theenvironment. The aim of this study was to investigate drug utilization patterns of analgesics in relation toenvironmental hazard in the region surrounding Sweden’s largest drinking water source, Lake Mälaren. This wasexamined using sales data on pharmaceuticals from the Swedish E-health Agency. The total sales of analgesics(non-steroidal anti-inflammatory drugs, paracetamol, other non-opioid analgesics, and opioids) for both humanand veterinary use in the region were analyzed for the years 2016 to 2020, in relation to the inherent environmental hazard for each active pharmaceutical ingredient (API). We found that a total of 454 tons of analgesicswere sold in the region during these 5 years. Classifications of environmental hazard were available for 16 out ofthe 45 studied APIs, accounting for 98.8% of the total mass in kilograms. Paracetamol, ibuprofen, and acetylsalicylic acid, which are all classified as low-hazard compounds, were the most commonly sold APIs. Diclofenac, the only pharmaceutical classified as high-hazard, was the fifth most commonly sold API, with a total soldmass of 2321 kg. The majority of the total sold mass of analgesics originated from dispensed prescriptions forhuman use in urban areas. Visualization of drug sales for humans and animals in different settings can be used toidentify the environmental burden of pharmaceuticals. Based on our study, we suggest that additional measuresto reduce the impacts of pharmaceuticals on the environment should primarily be directed to prescribing physicians in urban areas and campaigns targeted at the high over-the-counter sales of diclofenac. Moreover, it isimportant to address the fact that many pharmaceuticals currently have limited data on environmental hazard.
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