PUBLICATION
Physiologically Based Toxicokinetic Modeling of Bisphenols in Zebrafish (Danio rerio) Accounting for Variations in Metabolic Rates, Brain Distribution, and Liver Accumulation
- Authors
- Chelcea, I., Örn, S., Hamers, T., Koekkoek, J., Legradi, J., Vogs, C., Andersson, P.L.
- ID
- ZDB-PUB-220708-10
- Date
- 2022
- Source
- Environmental science & technology 56(14): 10216-10228 (Journal)
- Registered Authors
- Legradi, Jessica
- Keywords
- PBTK, biotransformation, bisphenols, endocrine disruptors, zebrafish
- MeSH Terms
-
- Animals
- Benzhydryl Compounds/toxicity
- Brain
- Female
- Humans
- Liver/metabolism
- Phenols
- Toxicokinetics
- Water Pollutants, Chemical*/metabolism
- Water Pollutants, Chemical*/toxicity
- Zebrafish*/metabolism
- PubMed
- 35797464 Full text @ Env. Sci. Tech.
Citation
Chelcea, I., Örn, S., Hamers, T., Koekkoek, J., Legradi, J., Vogs, C., Andersson, P.L. (2022) Physiologically Based Toxicokinetic Modeling of Bisphenols in Zebrafish (Danio rerio) Accounting for Variations in Metabolic Rates, Brain Distribution, and Liver Accumulation. Environmental science & technology. 56(14):10216-10228.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping