Master’s project at Swetox Södertälje: Toxicokinetic modeling of internal dose in zebrafish (Danio rerio) embryo

The zebrafish embryo is increasingly used as a vertebrate animal model to assess adverse effects of chemicals. The acceptance of such tests from a health risk assessment perspective relies on the possibility to extrapolate toxicity data from zebrafish embryo tests to humans, similar to the extrapolations from laboratory animals such as mice and rats carried out today.

Until now, little attention has been paid to the relation between external and internal dose in fish embryos. Detailed knowledge of the toxicokinetic processes including adsorption, biodistribution and the resulting target dose, and physiologically based toxicokinetic (PBTK) models are frequently used to characterize the internal dose and to extrapolate animal toxicity data to humans.

The aim of this study is to develop a better understanding of the toxicokinetics and target dose of chemical substances in the zebrafish embryo by a combination of experimental toxicokinetic studies and mathematical modeling.

More specifically, the study aims are: setting up analytical methods for determining time- and dose dependency of internal concentrations of perfluorinated compounds in zebrafish embryos; optimizing extraction procedures and exposure settings; and assessing biological effects of same exposures.

Methods used include: analytical techniques (HPLC, LC/MS); sample extraction techniques (liquid extraction, solid-phase extraction); and effect assessment: morphology scoring, gene expression (rt-qPCR).