关键词: 毒死蜱, PBTK/TD模型, 生长函数, 经口暴露, 年龄相关性

Abstract: OBJECTIVE: Build and validate PBTK/TD with growth function of the Juvenile rat following the oral exposure to chlorpyrifos(CPF). METHODS: Model construction and validation: to determine the model structure and parameters;establish the growth function of body weight for rats,and write the differential equations as well as the program. Using experimental data to optimize the model parameters,make Sensitivity Analysis and model validation. Animal experiment: 21 days-old female SD rats were randomly divided into 1 control group and 3 treated groups (12.5,25.0 and 50.0 mg/kg) according to the weight. Serum and cerebral cortex were collected after single gavage at 1h,3 h,6 h,12 h and 24 h,then to determine the concentration of CPF and 3,5,6-trichloropyridinol(TCP) in serum,the activity of acetylcholinesterase (AChE) in cerebral cortex. RESULTS: Experimental data showed that the concentrations of serum CPF and TCP increased to the peak level at the 3rd hour,then the concentrations decreased. With time,the activity of AChE in serum and cerebral cortex decreased first and then rose slowly. The minimum activity of serum AChE and cortex AChE was observed at 6th hour and 12th hour,respectively. The model predictions is consistent with the experimental results,while there were an overvalued or undervalued problem when using the model to make extrapolation. CONCLUSION: The model has reasonable structure and parameters,and can be used for extrapolation,especially in prediction of the individual average level,but the model still need further improvement.

Key words: chlorpyrifos, PBTK/TD model, growth function, oral exposure, age-dependent