{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T22:58:55Z","timestamp":1774133935534,"version":"3.50.1"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T00:00:00Z","timestamp":1747267200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100012774","name":"Innovation Fund Denmark","doi-asserted-by":"publisher","award":["9067-00032A"],"award-info":[{"award-number":["9067-00032A"]}],"id":[{"id":"10.13039\/100012774","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","award":["202106220074"],"award-info":[{"award-number":["202106220074"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Nontoxic blank samples are a prerequisite in effect-directed analysis to ensure that any measured bioassay activity stems from chemicals in the environmental sample, and not from chemicals added through the sampling and sample preparation procedures. In a study on wastewater, solid phase extraction (SPE) blank samples, prepared by extracting clean water (such as tap water, demineralized water, etc.) using the same methodology as real wastewater, showed toxic effects in algae, daphnia, and in vitro bioassays. The aim of this study was to pinpoint the origin of the chemicals responsible for the observed toxicity, and to provide guidance on how to remediate their occurrence. Analysis revealed that the elution solvents optimized for SPE, composed of methanol (MeOH), NH4OH, and formic acid, constituted a significant source of toxicity, even when evaporated to dryness. Ammonium was the primary source of toxicity in the algae assay. Formic acid released toxic metal ions from the system and SPE materials, particularly Cu and Zn, which strongly affected daphnia. Switching to pure MeOH as the elution solvent alleviated most of the toxicity, although some metals remained. Further reductions in toxicity were achieved by replacing ultra-pure water with an ion-rich artificial freshwater medium for preparing blank samples. Three tested SPE materials (graphitized carbon, hydrophilic\u2013lipophilic balance, and ENV+) released unidentified toxic chemicals correlating with algae toxicity and estrogen receptor activity, but these could be eliminated through extensive MeOH washing before packing the cartridges. Nontoxic levels of plasticizers were detected from system components. In conclusion, altering SPE elution solvents, washing SPE materials, and using artificial freshwater as blanks minimized the release of chemicals and ensured nontoxic blank samples.<\/jats:p>","DOI":"10.1093\/etojnl\/vgaf127","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T11:09:58Z","timestamp":1747307398000},"page":"2154-2165","source":"Crossref","is-referenced-by-count":1,"title":["The hidden toxicity of solid phase extraction blanks in water analysis"],"prefix":"10.1093","volume":"44","author":[{"given":"Yan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Plant and Environmental Sciences, University of Copenhagen , Frederiksberg,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mafalda","family":"Castro","sequence":"additional","affiliation":[{"name":"Department of Plant and Environmental Sciences, University of Copenhagen , Frederiksberg,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Selina","family":"Tisler","sequence":"additional","affiliation":[{"name":"Department of Plant and Environmental Sciences, University of Copenhagen , Frederiksberg,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathias B","family":"J\u00f8rgensen","sequence":"additional","affiliation":[{"name":"BIOFOS A\/S, Copenhagen,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristoffer","family":"Kilpinen","sequence":"additional","affiliation":[{"name":"Eurofins Environment Denmark A\/S, Vejen,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason","family":"Devers","sequence":"additional","affiliation":[{"name":"Department of Plant and Environmental Sciences, University of Copenhagen , Frederiksberg,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Austeja","family":"Luckute","sequence":"additional","affiliation":[{"name":"Department of Plant and Environmental Sciences, University of Copenhagen , Frederiksberg,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johan","family":"Lundqvist","sequence":"additional","affiliation":[{"name":"Department of Animal Biosciences, Swedish University of Agricultural Sciences , Uppsala,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan H","family":"Christensen","sequence":"additional","affiliation":[{"name":"Department of Plant and Environmental Sciences, University of Copenhagen , Frederiksberg,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nina","family":"Cedergreen","sequence":"additional","affiliation":[{"name":"Department of Plant and Environmental Sciences, University of Copenhagen , Frederiksberg,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,5,15]]},"reference":[{"key":"2025073101515028100_vgaf127-B1","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1577\/1548-8659(1948)78[96:TATOTT]2.0.CO;2","article-title":"The apparent thresholds of toxicity to Daphnia magna for chlorides of various metals when added to Lake Erie water","volume":"78","author":"Anderson","year":"1950","journal-title":"Transactions of the American Fisheries Society"},{"key":"2025073101515028100_vgaf127-B2","doi-asserted-by":"crossref","first-page":"3937","DOI":"10.1021\/ja01373a025","article-title":"Studies in diffusion. II. A kinetic theory of diffusion in liquid systems","volume":"52","author":"Arnold","year":"1930","journal-title":"Journal of the American Chemical Society"},{"key":"2025073101515028100_vgaf127-B3","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1080\/00103628909368129","article-title":"A manual colorimetric procedure for measuring ammonium nitrogen in soil and plant Kjeldahl digests","volume":"20","author":"Baethgen","year":"1989","journal-title":"Communications in Soil Science and Plant Analysis"},{"key":"2025073101515028100_vgaf127-B4","doi-asserted-by":"crossref","first-page":"122607","DOI":"10.1016\/j.watres.2024.122607","article-title":"Identification of polar bioactive substances in the Upper Rhine using effect-directed analysis","volume":"268","author":"Baygildiev","year":"2025","journal-title":"Water Research"},{"key":"2025073101515028100_vgaf127-B5","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.plantsci.2014.12.005","article-title":"Overcoming ammonium toxicity","volume":"231","author":"Bittsanszky","year":"2015","journal-title":"Plant Science"},{"key":"2025073101515028100_vgaf127-B6","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1016\/j.scitotenv.2015.11.102","article-title":"Effect-directed analysis supporting monitoring of aquatic environments\u2014An in-depth overview","volume":"544","author":"Brack","year":"2016","journal-title":"Science of the Total Environment"},{"key":"2025073101515028100_vgaf127-B7","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/978-3-642-18384-3_3","volume-title":"Effect-directed analysis of complex environmental contamination","author":"Brack","year":"2011"},{"key":"2025073101515028100_vgaf127-B8","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.chemosphere.2005.11.046","article-title":"Multi-generational effects of four selected environmental oestrogens on Daphnia magna","volume":"64","author":"Brennan","year":"2006","journal-title":"Chemosphere"},{"key":"2025073101515028100_vgaf127-B9","doi-asserted-by":"crossref","first-page":"e96580","DOI":"10.1371\/journal.pone.0096580","article-title":"Quantifying synergy: A systematic review of mixture toxicity studies within environmental toxicology","volume":"9","author":"Cedergreen","year":"2014","journal-title":"PLoS One"},{"key":"2025073101515028100_vgaf127-B10","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.marpolbul.2014.01.006","article-title":"Acclimation and toxicity of high ammonium concentrations to unicellular algae","volume":"80","author":"Collos","year":"2014","journal-title":"Marine Pollution Bulletin"},{"key":"2025073101515028100_vgaf127-B1160123","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1002\/etc.4944","article-title":"Effect-based trigger values for mixtures of chemicals in surface water detected with in vitro bioassays","volume":"40","author":"Escher","year":"2021","journal-title":"Environmental Toxicology and Chemistry"},{"key":"2025073101515028100_vgaf127-B11","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1039\/b517512g","article-title":"Passive sampling of herbicides combined with effect analysis in algae using a novel high-throughput phytotoxicity assay (Maxi-Imaging-PAM)","volume":"8","author":"Escher","year":"2006","journal-title":"Journal of Environmental Monitoring"},{"key":"2025073101515028100_vgaf127-B12","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1126\/science.aay6636","article-title":"Tracking complex mixtures of chemicals in our changing environment","volume":"367","author":"Escher","year":"2020","journal-title":"Science"},{"key":"2025073101515028100_vgaf127-B13","doi-asserted-by":"crossref","first-page":"7002","DOI":"10.1021\/es304793h","article-title":"Most oxidative stress response in water samples comes from unknown chemicals: The need for effect-based water quality trigger values","volume":"47","author":"Escher","year":"2013","journal-title":"Environmental Science & Technology"},{"key":"2025073101515028100_vgaf127-B14","doi-asserted-by":"crossref","first-page":"120147","DOI":"10.1016\/j.watres.2023.120147","article-title":"Effect-based evaluation of water quality in a system of indirect reuse of wastewater for drinking water production","volume":"242","author":"Frieberg","year":"2023","journal-title":"Water Research"},{"key":"2025073101515028100_vgaf127-B15","doi-asserted-by":"crossref","first-page":"2496","DOI":"10.1002\/etc.4873","article-title":"The combined algae test for the evaluation of mixture toxicity in environmental samples","volume":"39","author":"Glauch","year":"2020","journal-title":"Environmental Toxicology and Chemistry"},{"key":"2025073101515028100_vgaf127-B16","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1007\/s10493-019-00340-0","article-title":"Comparison of in-vitro bioassays for evaluation of the response of different stages of Rhipicephalus sanguineus sensu lato to calcium alginate encapsulated pheromone beads","volume":"77","author":"Gowrishankar","year":"2019","journal-title":"Experimental & Applied Acarology"},{"key":"2025073101515028100_vgaf127-B17","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.envint.2016.03.003","article-title":"Toxicity assessment using different bioassays and microbial biosensors","volume":"92-93","author":"Hassan","year":"2016","journal-title":"Environment International"},{"key":"2025073101515028100_vgaf127-B18","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1089\/aivt.2016.0021","article-title":"Avoiding false positives and optimizing identification of true negatives in estrogen receptor binding and agonist\/antagonist assays","volume":"3","author":"Hornung","year":"2017","journal-title":"Applied in Vitro Toxicology"},{"key":"2025073101515028100_vgaf127-B6336590","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.aca.2004.02.043","article-title":"Blank values, adsorption, pre-concentration, and sample preservation for arsenic speciation of environmental water samples","volume":"512","author":"Huang","year":"2004","journal-title":"Analytica Chimica Acta"},{"key":"2025073101515028100_vgaf127-B46","year":"2007"},{"key":"2025073101515028100_vgaf127-B19","first-page":"441","article-title":"Toxicity of wastewater from health care facilities assessed by different bioassays","volume":"39","author":"Jirova","year":"2018","journal-title":"Neuroendocrinology Letters"},{"key":"2025073101515028100_vgaf127-B20","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1021\/acs.est.8b02966","article-title":"TIMFIE sampler\u2013A new time-integrating, active, low-tech sampling device for quantitative monitoring of pesticides in whole water","volume":"53","author":"Jonsson","year":"2019","journal-title":"Environmental Science & Technology"},{"key":"2025073101515028100_vgaf127-B21","doi-asserted-by":"crossref","first-page":"121107","DOI":"10.1007\/s11356-023-30331-z","article-title":"Catchment area, fate, and environmental risks investigation of micropollutants in Danish wastewater","volume":"30","author":"Kilpinen","year":"2023","journal-title":"Environmental Science and Pollution Research International"},{"key":"2025073101515028100_vgaf127-B22","doi-asserted-by":"crossref","first-page":"23872","DOI":"10.1007\/s11356-017-0018-y","article-title":"The acute toxicity of bisphenol A and lignin-derived bisphenol in algae, daphnids, and Japanese medaka","volume":"24","author":"Li","year":"2017","journal-title":"Environmental Science and Pollution Research International"},{"key":"2025073101515028100_vgaf127-B23","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.biortech.2019.02.042","article-title":"A novel approach of using zeolite for ammonium toxicity mitigation and value-added Spirulina cultivation in wastewater","volume":"280","author":"Lu","year":"2019","journal-title":"Bioresource Technology"},{"key":"2025073101515028100_vgaf127-B24","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s12302-024-00875-z","article-title":"Effect-based monitoring of chemical hazards in drinking water from source to tap: Seasonal trends over 2 years of sampling","volume":"36","author":"Lundqvist","year":"2024","journal-title":"Environmental Sciences Europe"},{"key":"2025073101515028100_vgaf127-B25","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s12302-020-00326-5","article-title":"Mixture toxicity in the Erft river: Assessment of ecological risks and toxicity drivers","volume":"32","author":"Markert","year":"2020","journal-title":"Environmental Sciences Europe"},{"key":"2025073101515028100_vgaf127-B26","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1016\/j.watres.2017.07.016","article-title":"Development of a bioanalytical test battery for water quality monitoring: Fingerprinting identified micropollutants and their contribution to effects in surface water","volume":"123","author":"Neale","year":"2017","journal-title":"Water Research"},{"key":"2025073101515028100_vgaf127-B27","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1039\/C7EM00555E","article-title":"Solid-phase extraction as sample preparation of water samples for cell-based and other in vitro bioassays","volume":"20","author":"Neale","year":"2018","journal-title":"Environmental Science. Processes & Impacts"},{"key":"2025073101515028100_vgaf127-B28","doi-asserted-by":"crossref","first-page":"13197","DOI":"10.1021\/acs.est.0c05124","article-title":"Mixture risk drivers in freshwater sediments and their bioavailability determined using passive equilibrium sampling","volume":"54","author":"Niu","year":"2020","journal-title":"Environmental Science & Technology"},{"key":"2025073101515028100_vgaf127-B29","first-page":"328","volume-title":"Modelling heavy metal contamination events in water distribution systems","author":"Ohar","year":"2015"},{"key":"2025073101515028100_vgaf127-B30","doi-asserted-by":"crossref","first-page":"176728","DOI":"10.1016\/j.scitotenv.2024.176728","article-title":"Environmental occurrence and ecotoxicological risks of plastic leachates in aquatic and terrestrial environments","volume":"954","author":"Omidoyin","year":"2024","journal-title":"Science of the Total Environment"},{"key":"2025073101515028100_vgaf127-B31","author":"Organisation for Economic Co-operation and Development (OECD)","year":"2004"},{"key":"2025073101515028100_vgaf127-B32","author":"Organisation for Economic Co-operation and Development (OECD)","year":"2011"},{"key":"2025073101515028100_vgaf127-B33","doi-asserted-by":"crossref","first-page":"954626","DOI":"10.5402\/2011\/954626","article-title":"Analysis of ammonia toxicity in landfill leachates","volume":"2011","author":"Osada","year":"2011","journal-title":"ISRN Toxicology"},{"key":"2025073101515028100_vgaf127-B34","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S1532-0456(02)00112-6","article-title":"The biotic ligand model: A historical overview","volume":"133","author":"Paquin","year":"2002","journal-title":"Comparative Biochemistry and Physiology. Toxicology & Pharmacology"},{"key":"2025073101515028100_vgaf127-B92926998","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.watres.2014.08.053","article-title":"A review on emerging contaminants in wastewaters and the environment: Current knowledge, understudied areas and recommendations for future monitoring","volume":"72","author":"Petrie","year":"2015","journal-title":"Water Research"},{"key":"2025073101515028100_vgaf127-B35","first-page":"40","article-title":"Integrated systems of monitoring and controlling wastewater quality","volume":"64","author":"Pricop","year":"2013","journal-title":"Industria Textila"},{"key":"2025073101515028100_vgaf127-B2405873","year":"2021","journal-title":"Statistical Computing"},{"key":"2025073101515028100_vgaf127-B36","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.scitotenv.2016.12.140","article-title":"Assessment of a novel device for onsite integrative large-volume solid phase extraction of water samples to enable a comprehensive chemical and effect-based analysis","volume":"581","author":"Schulze","year":"2017","journal-title":"Science of the Total Environment"},{"key":"2025073101515028100_vgaf127-B37","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1021\/es5002105","article-title":"Identifying small molecules via high resolution mass spectrometry: Communicating confidence","volume":"48","author":"Schymanski","year":"2014","journal-title":"Environmental Science & Technology"},{"key":"2025073101515028100_vgaf127-B38","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1093\/toxsci\/55.1.107","article-title":"Ah receptor-based chemical screening bioassays: Application and limitations for the detection of Ah receptor agonists","volume":"55","author":"Seidel","year":"2000","journal-title":"Toxicological Sciences"},{"key":"2025073101515028100_vgaf127-B39","first-page":"052054","article-title":"Di-(2-ethylhexyl) phthalate induced the growth inhibition and oxidative damage in the microalga Chlorella vulgaris","volume":"227","author":"Shen","year":"2019","journal-title":"IOP Conference Series: Earth and Environmental Science"},{"key":"2025073101515028100_vgaf127-B40","doi-asserted-by":"crossref","first-page":"136383","DOI":"10.1016\/j.jhazmat.2024.136383","article-title":"Towards realism in hazard assessment of plastic and rubber leachates\u2014Methodological considerations","volume":"480","author":"S\u00f8rensen","year":"2024","journal-title":"Journal of Hazardous Materials"},{"key":"2025073101515028100_vgaf127-B41","doi-asserted-by":"crossref","first-page":"3300","DOI":"10.1016\/j.watres.2013.03.011","article-title":"Mixture effects of organic micropollutants present in water: Towards the development of effect-based water quality trigger values for baseline toxicity","volume":"47","author":"Tang","year":"2013","journal-title":"Water Research"},{"key":"2025073101515028100_vgaf127-B42","doi-asserted-by":"crossref","first-page":"118599","DOI":"10.1016\/j.watres.2022.118599","article-title":"From data to reliable conclusions: Identification and comparison of persistent micropollutants and transformation products in 37 wastewater samples by non-target screening prioritization","volume":"219","author":"Tisler","year":"2022","journal-title":"Water Research"},{"key":"2025073101515028100_vgaf127-B43","doi-asserted-by":"crossref","first-page":"8432","DOI":"10.1021\/acs.analchem.1c00357","article-title":"Correction of matrix effects for reliable non-target screening LC-ESI-MS analysis of wastewater","volume":"93","author":"Tisler","year":"2021","journal-title":"Analytical Chemistry"},{"key":"2025073101515028100_vgaf127-B44","doi-asserted-by":"crossref","first-page":"119758","DOI":"10.1016\/j.envpol.2022.119758","article-title":"Non-target screening of micropollutants and transformation products for assessing AOP-BAC treatment in groundwater","volume":"309","author":"Tisler","year":"2022","journal-title":"Environmental Pollution"},{"key":"2025073101515028100_vgaf127-B45","doi-asserted-by":"crossref","first-page":"2575","DOI":"10.1021\/acs.est.9b06379","article-title":"Toward a global understanding of chemical pollution: A first comprehensive analysis of national and regional chemical inventories","volume":"54","author":"Wang","year":"2020","journal-title":"Environmental Science & Technology"}],"container-title":["Environmental Toxicology and Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/etc\/advance-article-pdf\/doi\/10.1093\/etojnl\/vgaf127\/63196733\/vgaf127.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/etc\/article-pdf\/44\/8\/2154\/63196733\/vgaf127.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/etc\/article-pdf\/44\/8\/2154\/63196733\/vgaf127.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T05:52:07Z","timestamp":1753941127000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/etc\/article\/44\/8\/2154\/8132955"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,15]]},"references-count":50,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,5,15]]},"published-print":{"date-parts":[[2025,8,1]]}},"URL":"https:\/\/doi.org\/10.1093\/etojnl\/vgaf127","relation":{},"ISSN":["0730-7268","1552-8618"],"issn-type":[{"value":"0730-7268","type":"print"},{"value":"1552-8618","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,8]]},"published":{"date-parts":[[2025,5,15]]}}}