New Conceptual Toxicokinetic Model to Assess Synergistic Mixture Effects between the Aromatic Hydrocarbon β-Naphthoflavone and the Azole Nocodazole on the CYP1A Biomarker in a Fish Cell Line
| Autor: | Håvard G. Frøysa, Marie Mlnaříková, Charlotte Alvord, Shirin Fallahi, Guttorm Alendal, Malin Celander, Thorbjörn Lundh |
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| Rok vydání: | 2020 |
| Předmět: |
Azoles
Hydrocarbons Aromatic Article Cell Line chemistry.chemical_compound beta-Naphthoflavone Cytochrome P-450 CYP1A1 Animals Environmental Chemistry Toxicokinetics chemistry.chemical_classification biology Nocodazole Cytochrome P450 General Chemistry Enzyme Receptors Aryl Hydrocarbon chemistry biology.protein Biophysics Identifiability Azole Aromatic hydrocarbon Biomarkers Function (biology) |
| Zdroj: | Environmental Science and Technology 13748-13758 Environmental Science & Technology |
| ISSN: | 1520-5851 0013-936X |
| Popis: | Toxicokinetic interactions with catabolic cytochrome P450 (CYP) enzymes can inhibit chemical elimination pathways and cause synergistic mixture effects. We have created a mathematical bottom-up model for a synergistic mixture effect where we fit a multidimensional function to a given data set using an auxiliary nonadditive approach. The toxicokinetic model is based on the data from a previous study on a fish cell line, where the CYP1A enzyme activity was measured over time after exposure to various combinations of the aromatic hydrocarbon β-naphthoflavone and the azole nocodazole. To describe the toxicokinetic mechanism in this pathway and how that affects the CYP1A biomarker, the model uses ordinary differential equations. Local sensitivity and identifiability analyses revealed that all the 10 parameters estimated in the model were identified uniquely while fitting the model to the data for measuring the CYP1A enzyme activity. The model has a good prediction power and is a promising tool to test the synergistic toxicokinetic interactions between different chemicals. publishedVersion |
| Databáze: | OpenAIRE |
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