Physiology-informed toxicokinetic model for the zebrafish embryo test developed for bisphenols Show others and affiliations
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-215957 DOI: 10.1016/j.chemosphere.2023.140399 PubMedID: 37839743 Scopus ID: 2-s2.0-85174674618 OAI: oai:DiVA.org:umu-215957 DiVA, id: diva2:1808141
Funder Swedish Research Council, 2019-01838 Swedish Research Council, 2017-01036 The Kempe Foundations 2023-10-302023-10-302023-10-30 Bibliographically approved