Effect-based tools for monitoring estrogenic mixtures: Evaluation of five in vitro bioassays

Kunz, Petra; Simon, Eszter; Creusot, Nicolas; Jayasinghe, B. Sumith; Kienle, Cornelia; Maletz, Sibylle; Schifferli, Andrea; Schönlau, Christine; Aı̈t-Aı̈ssa, Sélim; Denslow, Nancy D.; Hollert, Henner; Werner, Inge; Vermeirssen, Etiënne L.M.

doi:10.1016/j.watres.2016.10.062

Cited by 66 publications

(51 citation statements)

References 42 publications

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“…The exposure duration (96 h for the Cyp19a1b-GFP assay and h for the ChgH-GFP assay), the tissue context (brain versus liver) and the metabolic capacity of the models may account for these differences. The variability in responsiveness and sensitivity of the many different estrogenicity assays is well known (Kunz et al 2017) and can be used to investigate the exact toxic mechanisms and to differentiate true effects from assay interferences (Browne et al 2015. In turn this does not mean that for water quality monitoring that many different assays indicative of the one endpoint should be used or that one assay should be favored over others.…”

Section: Comparing Cellular Effects With Whole Organism Specific Effectsmentioning

confidence: 99%

Development of a bioanalytical test battery for water quality monitoring: Fingerprinting identified micropollutants and their contribution to effects in surface water

et al. 2017

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Surface waters can contain a diverse range of organic pollutants, including pesticides, pharmaceuticals and industrial compounds. While bioassays have been used for water quality monitoring, there is limited knowledge regarding the effects of individual micropollutants and their relationship to the overall mixture effect in water samples. In this study, a battery of in vitro bioassays based on human and fish cell lines and whole organism assays using bacteria, algae, daphnids and fish embryos was assembled for use in water quality monitoring. The selection of bioassays was guided by the principles of adverse outcome pathways in order to cover relevant steps in toxicity pathways known to be triggered by environmental water samples. The effects of 34 water pollutants, which were selected based on hazard quotients, available environmental quality standards and mode of action information, were fingerprinted in the bioassay test battery. There was a relatively good agreement between the experimental results and available literature effect data. The majority of the chemicals were active in the assays indicative of apical effects, while fewer chemicals had a response in the specific reporter gene assays, but these effects were typically triggered at lower concentrations. The single chemical effect data were used to improve published mixture toxicity modeling of water samples from the Danube River. While there was a slight increase in the fraction of the bioanalytical equivalents explained for the Danube River samples, for some endpoints less than 1% of the observed effect could be explained by the studied chemicals. The new mixture models essentially confirmed previous findings from many studies monitoring water quality using both chemical analysis and bioanalytical tools. In short, our results indicate that many more chemicals contribute to the biological effect than those that are typically quantified by chemical monitoring programs or those regulated by environmental quality standards. This study not only demonstrates the utility of fingerprinting single chemicals for an improved understanding of the biological effect of pollutants, but also highlights the need to apply bioassays for water quality monitoring in order to prevent underestimation of the overall biological effect.

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Section: Comparing Cellular Effects With Whole Organism Specific Effectsmentioning

confidence: 99%

Development of a bioanalytical test battery for water quality monitoring: Fingerprinting identified micropollutants and their contribution to effects in surface water

et al. 2017

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“…An important issue concerning effect-based in vitro assays is the calculation of reliable EEQs of the analyzed samples. Several approaches for the calculation are applied and described in various publications (Kunz et al 2017, Gehrmann et al 2016, Escher et al 2008. If the effective concentration values of the sample dose-response curve are used (e.g.…”

Section: Sample Matrix Effects and Calculation Of Eeqmentioning

confidence: 99%

Validation of Arxula Yeast Estrogen Screen assay for detection of estrogenic activity in water samples: Results of an international interlaboratory study

Hettwer¹,

Jähne²,

Frost³

et al. 2018

Science of The Total Environment

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Endocrine-active substances can adversely impact the aquatic ecosystems. A special emphasis is laid, among others, on the effects of estrogens and estrogen mimicking compounds. Effect-based screening methods like in vitro bioassays are suitable tools to detect and quantify endocrine activities of known and unknown mixtures. This study describes the validation of the Arxula-Yeast Estrogen Screen (A-YES®) assay, an effect-based method for the detection of the estrogenic potential of water and waste water. This reporter gene assay, provided in ready to use format, is based on the activation of the human estrogen receptor alpha. The user-friendly A-YES® enables inexperienced operators to rapidly become competent with the assay. Fourteen laboratories from four countries with different training levels analyzed 17β-estradiol equivalent concentrations (EEQ) in spiked and unspiked waste water effluent and surface water samples, in waste water influent and spiked salt water samples and in a mixture of three bisphenols. The limit of detection (LOD) for untreated samples was 1.8ng/L 17β-estradiol (E2). Relative repeatability and reproducibility standard deviation for samples with EEQ above the LOD (mean EEQ values between 6.3 and 20.4ng/L) ranged from 7.5 to 21.4% and 16.6 to 28.0%, respectively. Precision results are comparable to other frequently used analytical methods for estrogens. The A-YES® has been demonstrated to be an accurate, precise and robust bioassay. The results have been included in the ISO draft standard. The assay was shown to be applicable for testing of typical waste water influent, effluent and saline water. Other studies have shown that the assay can be used with enriched samples, which lower the LOD to the pg/L range. The validation of the A-YES® and the development of a corresponding international standard constitute a step further towards harmonized and reliable bioassays for the effect-based analysis of estrogens and estrogen-like compounds in water samples.

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“…Within the NORMAN Network on Emerging Pollutants and the Solutions EU project a draft of a common position on how to use EBMs for water quality monitoring is recently under development (i.e. methodology to define effect-based trigger values; recommendations for a common battery of bioassays; quality/performance criteria for the benchmarking of bioassays) [ 14 – 16 , 19 – 21 , 54 , 61 – 63 ] and will be suggested directly to the EBM working group within the Common Implementation Strategy (CIS) for the WFD. In a recently published European-wide proof-of-principle study, the reliability of EBMs for screening of endocrine disrupting compounds was analyzed to harmonise monitoring and data interpretation methods, and to contribute to the current WFD review process.…”

Section: Effect-based Monitoring For Toxicity Fingerprintsmentioning

confidence: 99%

“…Batteries of EBMs have been applied in the framework of the project SOLUTIONS [ 11 , 12 ] in the Danube River basin [ 76 , 77 ] as well as in small streams in Switzerland [ 62 ]. In vitro EBMs for estrogenic receptor-mediated effects have been thoroughly validated for screening of endocrine disruptors in surface and waste waters [ 78 ] and artificial mixtures [ 63 ]. In situ tools like the PICT-approach have been successfully applied to demonstrate effects of complex mixtures on ambient communities [ 79 ] and the success of restoration efforts in WWTPs [ 80 ].…”

Section: Effect-based Monitoring For Toxicity Fingerprintsmentioning

confidence: 99%

Towards a holistic and solution-oriented monitoring of chemical status of European water bodies: how to support the EU strategy for a non-toxic environment?

et al. 2018

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The definition of priority substances (PS) according to the Water Framework Directive (WFD) helped to remove many of these chemicals from the market and to reduce their concentrations in the European water bodies. However, it could not prevent that many of these chemicals have been replaced by others with similar risks. Today, monitoring of the PS-based chemical status according to WFD covers only a tiny fraction of toxic risks, extensively ignores mixture effects and lacks incentives and guidance for abatement. Thus, we suggest complement this purely status-related approach with more holistic and solution-oriented monitoring, which at the same time helps to provide links to the ecological status. Major elements include (1) advanced chemical screening techniques supporting mixture risk assessment and unraveling of source-related patterns in complex mixtures, (2) effect-based monitoring for the detection of groups of chemicals with similar effects and the establishment of toxicity fingerprints, (3) effect-directed analysis of drivers of toxicity and (4) to translate chemical and toxicological fingerprints into chemical footprints for prioritization of management measures. The requirement of more holistic and solution-oriented monitoring of chemical contamination is supported by the significant advancement of appropriate monitoring tools within the last years. Non-target screening technology, effect-based monitoring and basic understanding of mixture assessment are available conceptually and in research but also increasingly find their way into practical monitoring. Substantial progress in the development, evaluation and demonstration of these tools, for example, in the SOLUTIONS project enhanced their acceptability. Further advancement, integration and demonstration, extensive data exchange and closure of remaining knowledge gaps are suggested as high priority research needs for the next future to bridge the gap between insufficient ecological status and cost-efficient abatement measures.

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Effect-based tools for monitoring estrogenic mixtures: Evaluation of five in vitro bioassays

Cited by 66 publications

References 42 publications

Development of a bioanalytical test battery for water quality monitoring: Fingerprinting identified micropollutants and their contribution to effects in surface water

Development of a bioanalytical test battery for water quality monitoring: Fingerprinting identified micropollutants and their contribution to effects in surface water

Validation of Arxula Yeast Estrogen Screen assay for detection of estrogenic activity in water samples: Results of an international interlaboratory study

Towards a holistic and solution-oriented monitoring of chemical status of European water bodies: how to support the EU strategy for a non-toxic environment?

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