Abstract
Effect-directed analysis (EDA) has shown its added value for the detection and identification of compounds with varying toxicological properties in water quality research. However, for routine toxicity assessment of multiple toxicological endpoints, current EDA is considered labor intensive and time consuming. To achieve faster EDA and identification, a high-throughput (HT) EDA platform, coupling a downscaled luminescent Ames and cell-based reporter gene assays with a high-resolution fraction collector and UPLC-QTOF MS, was developed. The applicability of the HT-EDA platform in the analysis of aquatic samples was demonstrated by analysis of extracts from WWTP influent, effluent and surface water. Downscaled assays allowed detection of mutagenicity and androgen, estrogen and glucocorticoid agonism following high-resolution fractionation in 228 fractions. From 8 masses tentatively identified through non-target analysis, 2 masses were further investigated and chemically and biologically confirmed as the mutagen 1,2,3-benzotriazole and the androgen androstenedione. The compatibility of the high-throughput EDA platform with analysis of water samples and the incorporation of mutagenic and endocrine disruption endpoints allow for future application in routine monitoring in drinking water quality control and improved identification of (emerging) mutagens and endocrine disruptors.
| Original language | English |
|---|---|
| Article number | 115204 |
| Pages (from-to) | 1-9 |
| Number of pages | 9 |
| Journal | Water Research |
| Volume | 168 |
| Early online date | 16 Oct 2019 |
| DOIs | |
| Publication status | Published - 1 Jan 2020 |
Funding
Hyphenation of the downscaled luminescent Ames test and cell-based reporter gene assays to a high-resolution fractionation setup enabled detection of mutagenicity and endocrine disruptive potency in sample fractions, respectively. Mutagenicity, and AR, ER and GR activity could be analyzed in 228 fractions collected from surface and WWTP influent/effluent water extracts and were detected in all samples. The identification process could be improved through selection of masses detected in active fractions at the same retention time over multiple extracts, reducing the number of masses to analyze. Eight compounds were tentatively identified as active compounds from which BTA and androstenedione were further investigated and confirmed as active mutagen and androgen respectively. Introduction of the downscaled luminescent Ames test to the HT-EDA platform enables rapid detection of mutagenicity, in addition to endocrine disruption, at high resolution and allows future application in the detection and identification of (novel) (mutagenic) toxicants during (routine) monitoring of the drinking water production process. To fully exploit the power of HT-EDA the lack of standards for confirmation studies, such as in this case with DEG-BDCIPP, should be addressed, possibly with the support of regulatory bodies for instance by hosting a repository of compounds with e.g. a REACH dossier, or through mediation with industrial partners that use specific compounds in their manufactured (end)products that are not available elsewhere.The described research was funded by the Dutch Technology Foundation (STW), project number 12396. The authors acknowledge Prof. Michael Denison (UC Davis, CA, USA) for providing the VM7Luc4E2 cell line, BioDetection Systems B.V. (Netherlands) for providing the GR-CALUX cell line and Martine Rosielle and Dennis Kloes for technical contributions. The described research was funded by the Dutch Technology Foundation (STW) , project number 12396 . The authors acknowledge Prof. Michael Denison (UC Davis, CA, USA) for providing the VM7Luc4E2 cell line, BioDetection Systems B.V. (Netherlands) for providing the GR-CALUX cell line and Martine Rosielle and Dennis Kloes for technical contributions.
| Funders | Funder number |
|---|---|
| BTA | |
| Dutch Technology Foundation (STW | |
| University of California, Davis | |
| Stichting voor de Technische Wetenschappen | 12396 |
UN SDGs
This output contributes to the following UN Sustainable Development Goals (SDGs)
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SDG 6 Clean Water and Sanitation
Keywords
- Bioassay
- Effect-directed analysis
- Endocrine disruption
- High-resolution
- High-throughput
- Mutagenicity
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