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Physiology-informed toxicokinetic model for the zebrafish embryo test developed for bisphenols
Umeå University, Faculty of Science and Technology, Department of Chemistry.ORCID iD: 0000-0002-2129-5210
Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Box 7028, Uppsala, Sweden; Institute of Environmental Medicine, Karolinska Institutet, Solna, Sweden.
Amsterdam Institute for Life and Environment (A-LIFE), Vrije Universiteit Amsterdam, HV Amsterdam, Netherlands.
Amsterdam Institute for Life and Environment (A-LIFE), Vrije Universiteit Amsterdam, HV Amsterdam, Netherlands.
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2023 (English)In: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, Vol. 345, article id 140399Article in journal (Refereed) Published
Abstract [en]

Zebrafish embryos (ZFE) is a widely used model organism, employed in various research fields including toxicology to assess e.g., developmental toxicity and endocrine disruption. Variation in effects between chemicals are difficult to compare using nominal dose as toxicokinetic properties may vary. Toxicokinetic (TK) modeling is a means to estimate internal exposure concentration or dose at target and to enable extrapolation between experimental conditions and species, thereby improving hazard assessment of potential pollutants. In this study we advance currently existing TK models for ZFE with physiological ZFE parameters and novel experimental bisphenol data, a class of chemicals with suspected endocrine activity. We developed a five-compartment model consisting of water, plastic, chorion, yolk sack and embryo in which surface area and volume changes as well as the processes of biotransformation and blood circulation influence mass fluxes. For model training and validation, we measured internal concentrations in ZFE exposed individually to BPA, bisphenol AF (BPAF) and Z (BPZ). Bayesian inference was applied for parameter calibration based on the training data set of BPZ. The calibrated TK model predicted internal ZFE concentrations of the majority of external test data within a 5-fold error and half of the data within a 2-fold error for bisphenols A, AF, F, and tetrabromo bisphenol A (TBBPA). We used the developed model to rank the hazard of seven bisphenols based on predicted internal concentrations and measured in vitro estrogenicity. This ranking indicated a higher hazard for BPAF, BPZ, bisphenol B and C (BPB, BPC) than for BPA.

Place, publisher, year, edition, pages
Elsevier, 2023. Vol. 345, article id 140399
Keywords [en]
Bisphenols, Embryo, Endocrine disruptors, PBTK, Zebrafish
National Category
Environmental Sciences
Identifiers
URN: urn:nbn:se:umu:diva-215957DOI: 10.1016/j.chemosphere.2023.140399PubMedID: 37839743Scopus ID: 2-s2.0-85174674618OAI: oai:DiVA.org:umu-215957DiVA, id: diva2:1808141
Funder
Swedish Research Council, 2019-01838Swedish Research Council, 2017-01036The Kempe FoundationsAvailable from: 2023-10-30 Created: 2023-10-30 Last updated: 2023-10-30Bibliographically approved

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Chelcea, Ioana C.Sapounidou, MariaAndersson, Patrik L.

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