Analysis of the sensitivity of in vitro bioassays for androgenic, progestagenic, glucocorticoid, thyroid and estrogenic activity: Suitability for drinking and environmental waters

Leusch, Frédéric D.L.; Neale, Peta A.; Hebert, Armelle; Scheurer, Marco; Schriks, Merijn

doi:10.1016/j.envint.2016.12.014

Cited by 90 publications

(77 citation statements)

References 55 publications

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“…For biological analysis, stably transfected mammalian cell lines (GeneBLAzer PR-UAS-bla HEK293T and GR-UAS-bla HEK 293T) were used for PR-and GR-mediated responses due to their sensitivity to detect biological responses from surface waters (Leusch et al 2017). The detailed biological analysis procedure is described in the Supplemental Data, Section S1.…”

Section: Biological Analysismentioning

confidence: 99%

Effect‐Directed Analysis of Progestogens and Glucocorticoids at Trace Concentrations in River Water

Hashmi

Krauß

Escher

et al. 2019

Enviro Toxic and Chemistry

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Effect-based monitoring is increasingly applied to detect and-in conjunction with chemical analysis-to identify endocrine-disrupting compounds (EDCs) in the environment. Although this approach of effect-directed analysis has been successfully demonstrated for estrogenicity and androgenicity, data on progestogens and glucocorticoids driving endocrine disruption are quite limited. We investigated progestogenic and glucocorticoid activities in Danube River water receiving untreated wastewater from Novi Sad, Serbia. After a 2-step fractionation, all fractions were tested with reporter gene bioassays for agonistic and antagonistic hormonal responses at progestogenic and glucocorticoid hormone receptors as well as with target and nontarget analytical screening of active fractions by liquid chromatography-high-resolution mass spectrometry. Due to masking by cytotoxic mixture components, the effects could not be detected in the raw water extract but were unraveled only after fractionation. Target chemical screening of the fraction that was active in the progesterone receptor (PR) assay revealed that progesterone and megestrol acetate were predominant drivers of PR-mediated activity along with medroxyprogesterone, dihydrotestosterone, androsterone, and epiandrosterone. Hydrocortisone was detected at sub-ng/L concentration in the active fraction in the glucocorticoid receptor (GR) assay but could not explain a significant fraction of the observed GR activity. The present study indicates that effect-based monitoring is a powerful tool to detect EDCs in the aquatic environment but that fractionation may be required to avoid masking effects of mixture components. Future effect-directed analysis studies are required to better understand the occurrence of EDCs and masking compounds in different lipophilicity windows, to finally reduce fractionation requirements for monitoring to a smart clean-up. Environ

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Section: Biological Analysismentioning

confidence: 99%

Effect‐Directed Analysis of Progestogens and Glucocorticoids at Trace Concentrations in River Water

Hashmi

Krauß

Escher

et al. 2019

Enviro Toxic and Chemistry

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“…It needs to be established whether the candidate bioassay is compatible to test the effects of realistic low‐level mixtures in (concentrated) water extracts without interference of matrix effects, and if the sensitivity of the bioassay is sufficient to detect possible effects of chemicals at concentrations present in drinking water and its sources. For example, a recent study by Leusch et al () has demonstrated that the sensitivity of in vitro bioassays for endocrine activity ranges widely. Available bioassays have sufficient sensitivity for androgenic and estrogenic activity in drinking water.…”

Section: Empirical Evaluation Of a Candidate Bioassaymentioning

confidence: 99%

“…Therefore, it can be expected that the different approaches derive (slightly) different EBTs. Even though toxic equivalency approaches are based on the theory that chemicals act via a single well‐defined mechanism such as receptor activation, agonistic and antagonistic mechanisms can occur simultaneously (Leusch et al ). Effects may therefore deviate from those expected from concentration addition, and this may in particular be the case in more complex integrated (heterogeneous) in vitro bioassays.…”

Section: Effect‐based Trigger Values (Ebts)mentioning

confidence: 99%

Risk‐based approach in the revised European Union drinking water legislation: Opportunities for bioanalytical tools

Dingemans

Baken

Oost³

et al. 2018

Integr Envir Assess & Manag

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A plethora of in vitro bioassays are developed in the context of chemical risk assessment and clinical diagnostics to test effects on different biological processes. Such assays can also be implemented in effect-based monitoring (EBM) of (drinking) water quality alongside chemical analyses. Effects-based monitoring can provide insight into risks for the environment and human health associated with exposure to (unknown) complex, low-level mixtures of micropollutants, which fits in the risk-based approach that was recently introduced in the European Drinking Water Directive. Some challenges remain, in particular those related to selection and interpretation of bioassays. For water quality assessment, carcinogenesis, adverse effects on reproduction and development, effects on xenobiotic metabolism, modulation of hormone systems, DNA reactivity, and adaptive stress responses are considered the most relevant toxicological endpoints. An evaluation procedure of the applicability and performance of in vitro bioassays for water quality monitoring, based on existing information, has been developed, which can be expanded with guidelines for experimental evaluations. In addition, a methodology for the interpretation of in vitro monitoring data is required, because the sensitivity of specific in vitro bioassays in combination with sample concentration may lead to responses of chemicals (far) below exposure concentrations that are relevant for human health effects. Different approaches are proposed to derive effect-based trigger values (EBTs), including EBTs based on (1) relative ecotoxicity potency, (2) health-based threshold values for chronic exposure in humans and kinetics of reference chemicals, and (3) read-across from (drinking) water guideline values. Effects-based trigger values need to be chosen carefully in order to be sufficiently but not overly conservative to indicate potential health effects. Consensus on the crucial steps in the selection and interpretation of in vitro bioassay data will facilitate implementation and legal embedding in the context of water quality monitoring of such assays in EBM strategies. Integr Environ Assess Manag 2018;00:000-000. © 2018 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

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“…However, with the in vitro detection approach, it appears that a possible major mode of actions of TDCs, thyroid receptor activation, is not environmentally relevant. Further, while the reason for this is not yet clear, and particularly challenging, performance limitation of in vitro assays is highly probable, given the inherent cell type-induced variations in the sensitivity of the widely used in vitro assays to potential TDCs [6] [11].…”

Section: Introductionmentioning

confidence: 99%

“…However, while TR binding assays and reporter gene assays can both detect TDCs with potential to interfere with TR, only reporter gene assays can discriminate between agonist and antagonist activities. Currently, TR binding assays, and a variety of reporter gene assays usually with different cell line types[11], are majorly used in the detection of thyroid disrupting activities in wastewater and surface waters.…”

mentioning

confidence: 99%

Thyroid Disrupting Activities in Wastewater and Surface Waters: A Review of Their <i>in Vitro</i> Analyses

Imiuwa¹,

Ekperusi²

2019

JEP

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The developmental and reproductive effects of endocrine disruption on humans and wildlife rank among the most threatening of all environmental health concerns. Particularly vulnerable to chemical assaults are the hypothalamic-pituitary-gonadal (HPG) axis and the hypothalamic-pituitary-thyroid (HPT) axis of the endocrine system. While the effects of endocrine disrupting chemicals (EDCs) on the HPG axis have been the subject of intense research efforts, with comprehensive elucidation, a lot remains to be clarified on the effects of EDCs on thyroid functions. For instance, there are no clear-cut biomarkers of exposure and effects of thyroid disrupting chemicals (TDCs) in intact organisms. Consequently, a number of in vitro assays have been developed, and are particularly useful for the identification and mechanistic characterization of potential TDCs considering the increasing number of EDCs that are being released into the environment. However, with the in vitro assays, studies suggest that a plausible major mode of action of TDCs, thyroid hormone receptor (THR) agonist activity, is not environmentally relevant. Here, we reviewed in vitro detection of TDCs activities in wastewater and surface waters. Data strongly suggest that cell lines may be responsible for the less frequent detection of THR agonist activity in wastewater and surface water. It was concluded that the development of reporter gene assays with thyroid hormone function related cell lines, is required.

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Analysis of the sensitivity of in vitro bioassays for androgenic, progestagenic, glucocorticoid, thyroid and estrogenic activity: Suitability for drinking and environmental waters

Cited by 90 publications

References 55 publications

Effect‐Directed Analysis of Progestogens and Glucocorticoids at Trace Concentrations in River Water

Effect‐Directed Analysis of Progestogens and Glucocorticoids at Trace Concentrations in River Water

Risk‐based approach in the revised European Union drinking water legislation: Opportunities for bioanalytical tools

Thyroid Disrupting Activities in Wastewater and Surface Waters: A Review of Their <i>in Vitro</i> Analyses

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Analysis of the sensitivity of in vitro bioassays for androgenic, progestagenic, glucocorticoid, thyroid and estrogenic activity: Suitability for drinking and environmental waters

Cited by 90 publications

References 55 publications

Effect‐Directed Analysis of Progestogens and Glucocorticoids at Trace Concentrations in River Water

Effect‐Directed Analysis of Progestogens and Glucocorticoids at Trace Concentrations in River Water

Risk‐based approach in the revised European Union drinking water legislation: Opportunities for bioanalytical tools

Thyroid Disrupting Activities in Wastewater and Surface Waters: A Review of Their &lt;i&gt;in Vitro&lt;/i&gt; Analyses

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Thyroid Disrupting Activities in Wastewater and Surface Waters: A Review of Their <i>in Vitro</i> Analyses