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Studying interaction effects on toxicokinetics in zebrafish combining experimental and modelling approaches
Umeå University, Faculty of Science and Technology, Department of Chemistry.
Department of Animal Biosciences, Swedish University of Agricultural Sciences (SLU), Uppsala, Sweden.
Faculty of Science, Chemistry for Environment & Health, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
Faculty of Science, Chemistry for Environment & Health, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
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2025 (English)In: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 965, article id 178663Article in journal (Refereed) Published
Abstract [en]

Humans and wildlife are exposed to a complex mixture of anthropogenic chemicals of which only a few have been subjected to regulations. Chemical risk assessment is currently based on evaluating single chemicals, which is costly, time-consuming, and neglect toxicokinetic and toxicodynamic mixture effects. This study focused on interaction effects on the absorption, distribution, metabolism and excretion (ADME) processes of selected chemicals representing potential modulators of these processes. Adult female zebrafish (Danio rerio) were exposed to selected mixture of 11 chemicals and bioconcentration factors (BCFs) on tissue level were determined for 9 of them: bisphenol A (BPA), bisphenol AF (BPAF), bisphenol Z (BPZ), triclosan, tribromophenol, pentachlorophenol, heptafluorobutyric acid (PFBA), perfluorobutanesulfonic acid (PFBS), and perfluorooctanesulfonic acid (PFOS). Comparison of BCFs of bisphenols obtained from single chemical exposure experiments versus the current study revealed no statistically significant differences (p > 0.05), implying no mixture effects on kinetics of bisphenols at investigated concentrations. The same conclusion was reached using two physiologically based kinetic (PBK) models, developed for individual bisphenols and per- and polyfluoroalkyl substances (PFAS), showing good model fit for BPA, BPZ, BPAF, and PFOS. To simulate exposure scenarios where kinetic interaction effects may occur through competitive protein binding in blood, a new PBK model was developed. Simulations where zebrafish were dosed with BPA and BPZ, individually, and combined with varying levels of PFOS, showed that competitive binding to serum proteins alter tissue levels of bisphenols when levels of PFOS exceeded 1 μg/L. This indicates that chemicals acting in concert could perturb ADME but only at higher levels or in complex mixtures.

Place, publisher, year, edition, pages
Elsevier, 2025. Vol. 965, article id 178663
Keywords [en]
ADME, Bisphenol, Mixture, PBTK, PFAS
National Category
Environmental Sciences
Identifiers
URN: urn:nbn:se:umu:diva-236284DOI: 10.1016/j.scitotenv.2025.178663PubMedID: 39892242Scopus ID: 2-s2.0-85216583893OAI: oai:DiVA.org:umu-236284DiVA, id: diva2:1945179
Funder
Swedish Research Council, 2019-01838Swedish Research Council Formas, 2018-02264Available from: 2025-03-18 Created: 2025-03-18 Last updated: 2025-03-18Bibliographically approved

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CiteExportLink to record
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