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Research article2022Peer reviewedOpen access

Physiologically Based Toxicokinetic Modeling of Bisphenols in Zebrafish (Danio rerio) Accounting for Variations in Metabolic Rates, Brain Distribution, and Liver Accumulation

Chelcea, Ioana; Orn, Stefan; Hamers, Timo; Koekkoek, Jacco; Legradi, Jessica; Vogs, Carolina; Andersson, Patrik L.

Abstract

Bisphenol A (BPA) is an industrial chemical, which has raised human health and environmental concerns due to its endocrine-disrupting properties. BPA analogues are less well-studied despite their wide use in consumer products. These analogues have been detected in water and aquatic organisms around the world, with some analogues showing toxic effects in various species including fish. Here, we present novel organ-specific time-course distribution data of bisphenol Z (BPZ) in female zebrafish (Danio rerio), including concentrations in the ovaries, liver, and brain, a rarely sampled organ with high toxicological relevance. Furthermore, fish-specific in vitro biotransformation rates were determined for 11 selected bisphenols. A physiologically based toxicokinetic (PBTK) model was adapted for four of these bisphenols, which was able to predict levels in the gonads, liver, and brain as well as the whole body within a 2-5-fold error with respect to experimental data, covering several important target organs of toxicity. In particular, predicted liver concentrations improved compared to currently available PBTK models. Predicted data indicate that studied bisphenols mainly distribute to the carcass and gonads and less to the brain. Our model provides a tool to increase our understanding on the distribution and kinetics of a group of emerging pollutants.

Keywords

biotransformation; PBTK; zebrafish; bisphenols; endocrine disruptors

Published in

Environmental Science and Technology
2022, Volume: 56, number: 14, pages: 10216-10228 Publisher: AMER CHEMICAL SOC

      SLU Authors

    • Sustainable Development Goals

      SDG3 Good health and well-being
      SDG6 Clean water and sanitation

      UKÄ Subject classification

      Algebra and Logic

      Publication identifier

      DOI: https://doi.org/10.1021/acs.est.2c01292

      Permanent link to this page (URI)

      https://res.slu.se/id/publ/118619