title: A physiologically based toxicokinetic model for the zebrafish Danio rerio.
abstract: Zebrafish (Danio rerio) is a widely used model for toxicological studies, in particular those related to investigations on endocrine disruption. The development and regulatory use of in vivo and in vitro tests based on this species can be enhanced by toxicokinetic modeling. For this reason, we propose a physiologically based toxicokinetic (PBTK) model for zebrafish describing the uptake and disposition of organic chemicals. The model is based on literature data on zebrafish, other cyprinidae and other fish families, new experimental physiological information (volumes, lipids and water contents) obtained from zebrafish, and chemical-specific parameters predicted by generic models. The relevance of available models predicting the latter parameters was evaluated with respect to gill uptake and partition coefficients in zebrafish. This evaluation benefited from the fact that the influence of confounding factors such as body weight and temperature on ventilation rate was included in our model. The predictions for six chemicals (65 data points) yielded by our PBTK model were compared to available toxicokinetics data for zebrafish and 88% of them were within a factor of 5 of the corresponding experimental values. Sensitivity analysis highlighted that the 1-octanol/water partition coefficient, the metabolism rate, and all the parameters that enable the prediction of assimilation efficiency and partitioning of chemicals need to be precisely determined in order to allow an effective toxicokinetic modeling.
authors.affiliation: Unité Modèles pour l'Écotoxicologie et la Toxicologie (METO), INERIS, Parc Technologique Alata, BP2, 60550 Verneuil-en-Halatte, France.
authors.forename: Alexandre R R
authors.initials: AR
authors.lastname: Péry
authors.forename: James
authors.initials: J
authors.lastname: Devillers
authors.forename: Céline
authors.initials: C
authors.lastname: Brochot
authors.forename: Enrico
authors.initials: E
authors.lastname: Mombelli
authors.forename: Olivier
authors.initials: O
authors.lastname: Palluel
authors.forename: Benjamin
authors.initials: B
authors.lastname: Piccini
authors.forename: François
authors.initials: F
authors.lastname: Brion
authors.forename: Rémy
authors.initials: R
authors.lastname: Beaudouin
mesh_terms: D020003:1-Octanol; D000818:Animals; D002138:Calibration; D003530:Cyprinidae; D052244:Endocrine Disruptors; D005260:Female; D005399:Fishes; D005880:Gills / Q000187:drug effects; D008297:Male; D008954:Models, Biological; D009930:Organic Chemicals / Q000493:pharmacokinetics* / Q000633:toxicity; D014018:Tissue Distribution; D066007:Toxicokinetics; D014874:Water Pollutants, Chemical / Q000493:pharmacokinetics* / Q000633:toxicity*; D015027:Zebrafish / Q000502:physiology*
chemical_list: D052244:Endocrine Disruptors; D009930:Organic Chemicals; D014874:Water Pollutants, Chemical; D020003:1-Octanol