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Article ; Online: Correction: Estrogenic, androgenic, and genotoxic activities of zearalenone and deoxynivalenol in in vitro bioassays including exogenous metabolic activation.

Yu, Maria / Oskarsson, Agneta / Alexander, Jan / Lundqvist, Johan

2024

Language	English
Publishing date	2024-04-26
Publishing country	Germany
Document type	Published Erratum
ZDB-ID	14500-2
ISSN	1867-1632 ; 0178-7888
ISSN (online)	1867-1632
ISSN	0178-7888
DOI	10.1007/s12550-024-00535-4
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Article ; Online: Estrogenic, androgenic, and genotoxic activities of zearalenone and deoxynivalenol in in vitro bioassays including exogenous metabolic activation.

Yu, Maria / Oskarsson, Agneta / Alexander, Jan / Lundqvist, Johan

Mycotoxin research

2024

Abstract: Zearalenone (ZEN) and deoxynivalenol (DON) and their derivatives are well-known mycotoxins, which can occur not only in crops but also in water bodies, including drinking water sources. In vitro bioassays can be used to detect biological effects of ... ...

Abstract	Zearalenone (ZEN) and deoxynivalenol (DON) and their derivatives are well-known mycotoxins, which can occur not only in crops but also in water bodies, including drinking water sources. In vitro bioassays can be used to detect biological effects of hazardous compounds in water. To this, when studying biological effects and toxicity in vitro, metabolism is important to consider. In this study, ZEN, α-zearalenol (α-ZEL), DON, 3-acetyl DON, and 15-acetyl DON were evaluated in vitro for hormone receptor-mediated effects (estrogen receptor [ER] and androgen receptor [AR]) and genotoxicity (micronucleus assay) in the presence of an exogenous metabolic activation system (MAS). The ER bioassay proved to be a highly sensitive method to detect low concentrations of the ZEN compounds (EC
Language	English
Publishing date	2024-04-08
Publishing country	Germany
Document type	Journal Article
ZDB-ID	14500-2
ISSN	1867-1632 ; 0178-7888
ISSN (online)	1867-1632
ISSN	0178-7888
DOI	10.1007/s12550-024-00529-2
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Article: Impact of sample acidification and extract storage on hormone receptor-mediated and oxidative stress activities in wastewater.

Yu, Maria / Mandava, Geeta / Lavonen, Elin / Oskarsson, Agneta / Lundqvist, Johan

Journal of water and health

2024 Volume 22, Issue 1, Page(s) 169–182

Abstract: An underemphasized aspect of sampling strategies in effect-based in vitro testing is to determine suitable collection and preparation techniques. In the current study, the impact of sample acidification on bioactivities was assessed using in vitro ... ...

Abstract	An underemphasized aspect of sampling strategies in effect-based in vitro testing is to determine suitable collection and preparation techniques. In the current study, the impact of sample acidification on bioactivities was assessed using in vitro bioassays for hormone receptor-mediated effects (estrogen receptor [ER] and androgen receptor [AR]) and the oxidative stress response (Nrf2 activity). Sampling was conducted at a recently upgraded Swedish wastewater treatment plant. Future plans for the treated wastewater include reuse for irrigation or as a potential drinking water source. In the AR and Nrf2 assays, acidification decreased bioactivities in the wastewater influent sample extracts, whereas acidification increased bioactivities following further treatment (disc filtration). In the ER assay, acidification had no impact on the observed bioactivities in the sample extracts. A secondary objective of the study was to assess the stability of the sample extracts over time. Lower activities were detected in the ER and AR assays in all extracts after storage for approximately 1 year. Nrf2 activities did not decrease over time, but rather increased in some of the acidified sample extracts. Overall, the findings suggest that sampling strategies involving acidification may need to be tailored depending on the selected bioassay(s) and the type of wastewater treatments being assessed.
MeSH term(s)	Wastewater ; NF-E2-Related Factor 2 ; Receptors, Estrogen/metabolism ; Oxidative Stress ; Hydrogen-Ion Concentration ; Hormones ; Water Pollutants, Chemical/analysis ; Biological Assay/methods
Chemical Substances	Wastewater ; NF-E2-Related Factor 2 ; Receptors, Estrogen ; Hormones ; Water Pollutants, Chemical
Language	English
Publishing date	2024-01-31
Publishing country	England
Document type	Journal Article
ZDB-ID	2123845-5
ISSN	1996-7829 ; 1477-8920
ISSN (online)	1996-7829
ISSN	1477-8920
DOI	10.2166/wh.2023.266
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Article ; Online: Evaluation of in vitro bioassays as a screening tool to monitor chemical hazards in cow's milk.

Selin, Erica / Mandava, Geeta / Karlsson, Maria / Lundqvist, Johan

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association

2023 Volume 180, Page(s) 114025

Abstract: Studies on cow's milk have mainly focused on analyzing specific chemical groups and natural components. Therefore, in this study, we evaluated if effect-based in vitro methods could be used as a screening tool to monitor chemical hazards in milk. In ... ...

Abstract	Studies on cow's milk have mainly focused on analyzing specific chemical groups and natural components. Therefore, in this study, we evaluated if effect-based in vitro methods could be used as a screening tool to monitor chemical hazards in milk. In total, 32 milk samples were collected from a Swedish dairy company throughout one year. These samples included conventional and organic semi-skimmed as well as raw milk. The milk samples were tested in five in vitro methods covering eight endpoints. These endpoints included cytotoxicity, endocrine disruption (estrogen/androgen induction/inhibition), aryl hydrocarbon receptor activity, oxidative stress and DNA damage. Estrogen and androgen receptor inhibition, in addition to aryl hydrocarbon receptor activity, were the most responsive endpoints, where 10 to 13 out of the 32 milk samples were bioactive. Organic and conventional milk showed no major differences. Overall, no or only low activities were observed in milk samples in the remaining in vitro assays, which is a promising result with regard to applying effect-based methods as a screening tool. Concerning the most responsive assays, more research is needed to understand the normal background variations before they can be used as a screening tool for chemical hazards in milk.
Language	English
Publishing date	2023-09-07
Publishing country	England
Document type	Journal Article
ZDB-ID	782617-5
ISSN	1873-6351 ; 0278-6915
ISSN (online)	1873-6351
ISSN	0278-6915
DOI	10.1016/j.fct.2023.114025
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Article ; Online: Potentials and pitfalls of transient in vitro reporter bioassays: interference by vector geometry and cytotoxicity in recombinant zebrafish cell lines.

Lungu-Mitea, Sebastian / Lundqvist, Johan

Archives of toxicology

2020 Volume 94, Issue 8, Page(s) 2769–2784

Abstract: The water framework directive re-evaluation proposes the integration of effect-based tools, increasing the need for alternative methods. Especially within aquatic toxicology, coverage of specific toxicity pathways is scarce, and most applications are ... ...

Abstract	The water framework directive re-evaluation proposes the integration of effect-based tools, increasing the need for alternative methods. Especially within aquatic toxicology, coverage of specific toxicity pathways is scarce, and most applications are based on mammalian or bacterial models, not reflecting realistic exposure scenarios. The use of transient reporter gene assays in cells from organisms of interest could be a quick and inexpensive solution. However, interference with cellular homeostasis may impact the system beyond the function of the manipulated gene and thus lead to non-specific results. We describe how varying vector geometry and different regulatory gene elements on plasmids used for transfection in zebrafish hepatocytes and embryonic fibroblasts may lead up to a tenfold difference in potency. Cells were transiently co-transfected with an Nrf2-responsive Firefly luciferase reporter plasmid and eight different Renilla luciferase normalization plasmids. Transfected cells were exposed to two different regimes (0.1-100 µM and 7.8-250 µM) of the oxidative stress-inducing compounds, sulforaphane, tertbutylhydroquinone, and metazachlor. Nrf2 activity was measured in dual-luciferase assays. In parallel, cytotoxicity was assessed for different endpoints (energy metabolism, protein amount, membrane stability, and cell proliferation) in non-transfected cells and cells co-transfected with constructs of increasing size, to be used for normalization. Transfected cells were more susceptible to cytotoxicity in a vector size-dependent manner. Conclusively, we report that vector geometries (size, backbones, gene-regulatory units), cell line (tissue origin), applied transfection methods, and signal normalization may alter the sensitivity of reporter bioassays in a synergistic manner. Further, we propose that thorough bioassay design is needed to ensure reliability and regulatory acceptance.
Language	English
Publishing date	2020-05-23
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	124992-7
ISSN	1432-0738 ; 0340-5761
ISSN (online)	1432-0738
ISSN	0340-5761
DOI	10.1007/s00204-020-02783-6
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Article ; Online: Development, scrutiny, and modulation of transient reporter gene assays of the xenobiotic metabolism pathway in zebrafish hepatocytes.

Lungu-Mitea, Sebastian / Han, Yuxin / Lundqvist, Johan

Cell biology and toxicology

2021 Volume 39, Issue 3, Page(s) 991–1013

Abstract: The "toxicology in the twenty-first century" paradigm shift demands the development of alternative in vitro test systems. Especially in the field of ecotoxicology, coverage of aquatic species-specific assays is relatively scarce. Transient reporter gene ... ...

Abstract	The "toxicology in the twenty-first century" paradigm shift demands the development of alternative in vitro test systems. Especially in the field of ecotoxicology, coverage of aquatic species-specific assays is relatively scarce. Transient reporter gene assays could be a quick, economical, and reliable bridging technology. However, the user should be aware of potential pitfalls that are influenced by reporter vector geometry. Here, we report the development of an AhR-responsive transient reporter-gene assay in the permanent zebrafish hepatocytes cell line (ZFL). Additionally, we disclose how viral, constitutive promoters within reporter-gene assay cassettes induce squelching of the primary signal. To counter this, we designed a novel normalization vector, bearing an endogenous zebrafish-derived genomic promoter (zfEF1aPro), which rescues the squelching-delimited system, thus, giving new insights into the modulation of transient reporter systems under xenobiotic stress. Finally, we uncovered how the ubiquitously used ligand BNF promiscuously activates multiple toxicity pathways of the xenobiotic metabolism and cellular stress response in an orchestral manner, presumably leading to a concentration-related inhibition of the AhR/ARNT/XRE-toxicity pathway and non-monotonous concentration-response curves. We named such a multi-level inhibitory mechanism that might mask effects as "maisonette squelching." A transient reporter gene assay in zebrafish cell lines utilizing endogenous regulatory gene elements shows increased in vitro toxicity testing performance. Synthetic and constitutive promotors interfere with signal transduction ("squelching") and might increase cellular stress (cytotoxicity). The squelching phenomenon might occur on multiple levels (toxicity pathway crosstalk and normalization vector), leading to a complete silencing of the reporter signal.
MeSH term(s)	Animals ; Genes, Reporter ; Zebrafish/genetics ; Receptors, Aryl Hydrocarbon/genetics ; Receptors, Aryl Hydrocarbon/metabolism ; Xenobiotics/toxicity ; Hepatocytes/metabolism
Chemical Substances	Receptors, Aryl Hydrocarbon ; Xenobiotics
Language	English
Publishing date	2021-10-15
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	48824-0
ISSN	1573-6822 ; 0742-2091
ISSN (online)	1573-6822
ISSN	0742-2091
DOI	10.1007/s10565-021-09659-0
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Article ; Online: Comparison of the photocatalytic degradability of PFOA, PFOS and GenX using Fe-zeolite in water.

Wen, Junying / Li, Huarui / Ottosen, Lars Ditlev Mørck / Lundqvist, Johan / Vergeynst, Leendert

Chemosphere

2023 Volume 344, Page(s) 140344

Abstract: Knowledge on the photocatalytic degradability of the emerging poly- and perfluorinated alkyl substances (PFAS) in water, specifically GenX, is limited. GenX has been detected globally in river water and is considered potentially more toxic than legacy ... ...

Abstract	Knowledge on the photocatalytic degradability of the emerging poly- and perfluorinated alkyl substances (PFAS) in water, specifically GenX, is limited. GenX has been detected globally in river water and is considered potentially more toxic than legacy PFAS. In this study, we compared the photocatalytic degradability of GenX with the legacy compounds perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) using Fe-zeolite photocatalysts. After 7 h of irradiation, GenX showed lower removal (79%) and defluorination (33%) as compared to PFOA (100% removal and 69% defluorination) and PFOS (100% removal and 51% defluorination). The quasi-first-order degradation rate of GenX (1.5 h
MeSH term(s)	Zeolites ; Water ; Fluorocarbons ; Alkanesulfonic Acids ; Caprylates ; Carbon
Chemical Substances	perfluorooctanoic acid (947VD76D3L) ; perfluorooctane sulfonic acid (9H2MAI21CL) ; Zeolites (1318-02-1) ; Water (059QF0KO0R) ; Fluorocarbons ; Alkanesulfonic Acids ; Caprylates ; Carbon (7440-44-0)
Language	English
Publishing date	2023-10-04
Publishing country	England
Document type	Journal Article
ZDB-ID	120089-6
ISSN	1879-1298 ; 0045-6535 ; 0366-7111
ISSN (online)	1879-1298
ISSN	0045-6535 ; 0366-7111
DOI	10.1016/j.chemosphere.2023.140344
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Article ; Online: Integrating different tools and technologies to advance drinking water quality exposure assessments.

Schullehner, Jörg / Cserbik, Dora / Gago-Ferrero, Pablo / Lundqvist, Johan / Nuckols, John R

Journal of exposure science & environmental epidemiology

2023 Volume 34, Issue 1, Page(s) 108–114

Abstract: Contaminants in drinking water are a major contributor to the human exposome and adverse health effects. Assessing drinking water exposure accurately in health studies is challenging, as several of the following study design domains should be addressed ... ...

Abstract	Contaminants in drinking water are a major contributor to the human exposome and adverse health effects. Assessing drinking water exposure accurately in health studies is challenging, as several of the following study design domains should be addressed as adequately as possible. In this paper, we identify the domains Time, Space, Data Quality, Data Accessibility, economic considerations of Study Size, and Complex Mixtures. We present case studies for three approaches or technologies that address these domains differently in the context of exposure assessment of drinking water quality: regulated contaminants in monitoring databases, high-resolution mass spectrometry (HRMS)-based wide-scope chemical analysis, and effect-based bioassay methods. While none of these approaches address all the domains sufficiently, together they have the potential to carry out exposure assessments that would complement each other and could advance the state-of-science towards more accurate risk analysis. The aim of our study is to give researchers investigating health effects of drinking water quality the impetus to consider how their exposure assessments relate to the above-mentioned domains and whether it would be worthwhile to integrate the advanced technologies presented into planned risk analyses. We highly suggest this three-pronged approach should be further evaluated in health risk analyses, especially epidemiological studies concerning contaminants in drinking water. The state of the knowledge regarding potential benefits of these technologies, especially when applied in tandem, provides more than sufficient evidence to support future research to determine the implications of combining the approaches described in our case studies in terms of protection of public health.
MeSH term(s)	Humans ; Drinking Water ; Gas Chromatography-Mass Spectrometry ; Biological Assay ; Databases, Factual ; Exposome
Chemical Substances	Drinking Water
Language	English
Publishing date	2023-08-08
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2218551-3
ISSN	1559-064X ; 1559-0631
ISSN (online)	1559-064X
ISSN	1559-0631
DOI	10.1038/s41370-023-00588-0
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Article ; Online: Removal of oxidative stress and genotoxic activities during drinking water production by ozonation and granular activated carbon filtration

Yu, Maria / Lavonen, Elin / Oskarsson, Agneta / Lundqvist, Johan

Environ Sci Eur. 2021 Dec., v. 33, no. 1 p.124-124

2021

Abstract: BACKGROUND: Bioanalytical tools have been shown to be useful in drinking water quality assessments. Here, we applied a panel of in vitro bioassays to assess the treatment efficiency of two pilot-scale treatments: ozonation and granular activated carbon ( ... ...

Abstract	BACKGROUND: Bioanalytical tools have been shown to be useful in drinking water quality assessments. Here, we applied a panel of in vitro bioassays to assess the treatment efficiency of two pilot-scale treatments: ozonation and granular activated carbon (GAC) filtration at a drinking water treatment plant (DWTP). The pilot-scale systems were studied alongside a full-scale treatment process consisting of biological activated carbon (BAC) filtration, UV disinfection, and monochloramine dosing. Both systems were fed the same raw water treated with coagulation/flocculation/sedimentation and sand filtration. The endpoints studied were oxidative stress (Nrf2 activity), genotoxicity (micronuclei formations), aryl hydrocarbon receptor (AhR) activation, as well as estrogen receptor (ER) and androgen receptor (AR) activity. RESULTS: Nrf2, AhR, and ER activities and genotoxic effects were detected in the incoming raw water and variability was observed between the sampling events. Compared to most of the samples taken from the full-scale treatment system, lower Nrf2, AhR, and ER bioactivities as well as genotoxicity were observed in all samples from the pilot-scale systems across all sampling events. The most pronounced treatment effect was a 12-fold reduction in Nrf2 activity and a sixfold decrease in micronuclei formations following ozonation alone. GAC filtration alone resulted in sevenfold and fivefold reductions in Nrf2 activity and genotoxicity, respectively, in the same sampling event. Higher bioactivities were detected in most samples from the full-scale system suggesting a lack of treatment effect. No androgenic nor anti-androgenic activities were observed in any sample across all sampling events. CONCLUSIONS: Using effect-based methods, we have shown the presence of bioactive chemicals in the raw water used for drinking water production, including oxidative stress, AhR and ER activities as well as genotoxicity. The currently used treatment technologies were unable to fully remove the observed bioactivities. Ozonation and GAC filtration showed a high treatment efficiency and were able to consistently remove the bioactivities observed in the incoming water. This is important knowledge for the optimization of existing drinking water treatment designs and the utilization of alternative treatment technologies.
Keywords	activated carbon ; androgen receptors ; aryl hydrocarbon receptors ; coagulation ; disinfection ; estrogen receptors ; filtration ; flocculation ; genotoxicity ; hormone antagonists ; mutagens ; oxidative stress ; ozonation ; sand ; water quality ; water treatment ; Europe
Language	English
Dates of publication	2021-12
Size	p. 124.
Publishing place	Springer Berlin Heidelberg
Document type	Article ; Online
ZDB-ID	2593962-2
ISSN	2190-4715 ; 2190-4707
ISSN (online)	2190-4715
ISSN	2190-4707
DOI	10.1186/s12302-021-00567-y
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Glass-bottled drinking water: a time capsule to study the historic presence of hazardous chemicals using effect-based methods

Lundqvist, Johan / Persson, Kenneth M. / Oskarsson, Agneta

Environ Sci Eur. 2021 Dec., v. 33, no. 1 p.34-34

2021

Abstract: BACKGROUND: Contamination of drinking water by hazardous chemicals can be associated with human health risks. Recent studies using effect-based in vitro methods have demonstrated that a large part of the observed toxic effects are caused by unknown ... ...

Abstract	BACKGROUND: Contamination of drinking water by hazardous chemicals can be associated with human health risks. Recent studies using effect-based in vitro methods have demonstrated that a large part of the observed toxic effects are caused by unknown chemicals. In this study, we have used a panel of effect-based methods to study the presence of chemical contaminants in a unique material; glass-bottled Swedish tap water collected during the 1990s. These water samples were compared to drinking water from the same source waters and drinking water facilities, yet collected about 25 years later, in 2020. RESULTS: Samples were concentrated by solid phase extraction and evaluated for the following activities; estrogen receptor activity, androgen receptor activity, antiandrogenic activity, aryl hydrocarbon receptor activity, and oxidative stress response. We observed aryl hydrocarbon receptor activities in almost all studied samples and estrogen receptor activity in three out of ten studied samples. No activities were observed for androgen receptor activity, antiandrogenic activity or oxidative stress response. In general, observed activities were more frequent and higher in the water samples collected during the 1990s as compared to the corresponding samples collected in 2020. CONCLUSIONS: This study demonstrates that it is possible to conduct an effect-based evaluation of the presence of hazardous chemicals in drinking water, with as small starting volume as 330 mL, by using miniaturized bioassays. Further, by comparing the glass-bottled water samples with newly collected water samples from the same drinking water treatment facilities, our results indicate that the presence of aryl hydrocarbon receptor and estrogen receptor activating compounds in the drinking water has decreased over the approximately quarter of a century that is separating the two sampling occasions. This difference could be due to improved raw water quality and/or improved treatment efficiency in the treatment plants.
Keywords	androgen receptors ; aryl hydrocarbon receptors ; chemical pollutants ; estrogen receptors ; hormone antagonists ; human health ; oxidative stress ; solid phase extraction ; stress response ; tap water ; toxicity ; water quality ; water treatment ; Europe
Language	English
Dates of publication	2021-12
Size	p. 34.
Publishing place	Springer Berlin Heidelberg
Document type	Article ; Online
ZDB-ID	2593962-2
ISSN	2190-4715 ; 2190-4707
ISSN (online)	2190-4715
ISSN	2190-4707
DOI	10.1186/s12302-021-00476-0
Database	NAL-Catalogue (AGRICOLA)

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