A physiologically based toxicokinetics and toxicodynamics model in rats following both oral and subcutaneous exposure to chlorpyrifos
10.3867/j.issn.1000-3002.2016.01.011
- VernacularTitle:大鼠经胃和皮下暴露毒死蜱的毒物代谢动力学和毒效学模型构建
- Author:
Zhengying CAO
;
Xinya YAO
;
Minxian ZHAO
;
Cannan WANG
- Publication Type:Journal Article
- Keywords:
chlorpyrifos;
acetylcholinesterase;
toxicokinetics;
toxicodynamics;
mathematical model
- From:
Chinese Journal of Pharmacology and Toxicology
2016;(1):74-81
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To develop and validate a physiologically based toxicokinetics and toxico?dynamics(PBTK/TD)model for chlorpyrifos(CPF)in rats following both oral and subcutaneous expo?sures to CPF. METHODS ①A PBTK/TD model was established with toxicokinetics and toxicodynam?ics data in literature,which was used for predicting contents of CPF and 3,5,6-trichloro-2-pyridinol (TCP)in blood and activities of acetylcholine esterase(AChE)in the plasma and brain of rats exposed to CPF.②Rats were given 50 mg · kg-1 CPF oral and 50 mg · kg-1 CPF sc simultaneously. Blood and brain samples were collected at 0,1,2,4,6,8,12,24 and 48 h,respectively,after CPF administration (n=5). CPF And TCP contents in plasma,activities of AChE in the plasma and brain were deter?mined,and compared with the simulation values by PBTK/TD model in order to validate the accuracy of the model. RESULTS It was predicted by the PBTK/TD model that after the administration (oral+sc) of CPF 20+20,10+30 and (30+10)mg · kg-1,the concentrations of CPF and TCP in plasma increased and then decreased with time in each group. The inhibitory level of AChE activity in the plasma was orally dose-dependent,while AChE activity of the brain was more sensitive to CPF subcutaneous exposure. The simulation values obtained by the PBTK/TD model were not significantly different from the experimental values obtained by co-administered CPF at(50+50)mg · kg-1. CONCLUSION This CPF PBTK/TD model can quantitatively estimate target tissue dosimetry and AChE inhibition.
