title: Dynamical coupling of PBPK/PD and AUC-based toxicity models for arsenic in tilapia Oreochromis mossambicus from blackfoot disease area in Taiwan.
abstract: A physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) models were developed for arsenic (As) in tilapia Oreochromis mossambicus from blackfoot disease area in Taiwan. The PBPK/PD model structure consisted of muscle, gill, gut wall, alimentary canal, and liver, which were interconnected by blood circulation. We integrate the target organ concentrations and dynamic response describing uptake, metabolism, and disposition of As and the associated area-under-curve (AUC)-based toxicological dynamics following an acute exposure. The model validations were compared against the field observations from real tilapia farms and previously published uptake/depuration experimental data, indicating that predicted and measured As concentrations in major organs of tilapia were in good agreement. The model was utilized to reasonably simulate and construct a dose-dependent dynamic response between mortality effect and equilibrium target organ concentrations. Model simulations suggest that tilapia gills may serve as a surrogate sensitive biomarker of short-term exposure to As. This integrated As PBPK/PD/AUC model quantitatively estimates target organ concentration and dynamic response in tilapia and is a strong framework for future waterborne metal model development and for refining a biologically-based risk assessment for exposure of aquatic species to waterborne metals under a variety of scenarios.
authors.affiliation: Ecotoxicological Modeling Center, Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei, Taiwan 10617, ROC. cmliao@ntu.edu.tw
authors.forename: Chung-Min
authors.initials: CM
authors.lastname: Liao
authors.forename: Huang-Min
authors.initials: HM
authors.lastname: Liang
authors.forename: Bo-Ching
authors.initials: BC
authors.lastname: Chen
authors.forename: Sher
authors.initials: S
authors.lastname: Singh
authors.forename: Jeng-Wei
authors.initials: JW
authors.lastname: Tsai
authors.forename: Yun-Hua
authors.initials: YH
authors.lastname: Chou
authors.forename: Wen-Tze
authors.initials: WT
authors.lastname: Lin
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001151:Arsenic / Q000493:pharmacokinetics* / Q000633:toxicity; D020261:Arsenic Poisoning / Q000150:complications; D001681:Biological Assay / Q000379:methods; D004305:Dose-Response Relationship, Drug; D005506:Food Contamination / Q000032:analysis; D006801:Humans; D008954:Models, Biological; D016491:Peripheral Vascular Diseases / Q000139:chemically induced*; D018570:Risk Assessment / Q000379:methods; D017747:Seafood / Q000032:analysis; D017210:Tilapia / Q000378:metabolism*; D014018:Tissue Distribution; D014874:Water Pollutants, Chemical / Q000493:pharmacokinetics* / Q000633:toxicity
chemical_list: D014874:Water Pollutants, Chemical; D001151:Arsenic