癌变·畸变·突变Issue(5)：386-393,8.DOI:10.3969/j.issn.1004-616x.2015.05.013
应用PBTK/TD模型研究毒死蜱经口重复染毒幼年大鼠的毒代动力学及毒效应学
Toxicokinetics and toxicodynamics in juvenile rats following repeated oral exposure to chlorpyifos by using PBTK/TD model
摘要
Abstract
OBJECTIVE:To describe the characteristics of toxicokinetics and toxicodynamics of chlorpyifos (CPF) in juvenile rats after repeated oral gavage of chlorpyrifos by using PBTK/TD model.METHODS:21 days-old female SD rats were given daily gavage doses of CPF at doses of 0,1.0,2.5,5.0,10.0 and 15.0 mg/kg/d for 10 days. Serum and cerebral cortex were collected on days 3,6,10 and 11,to determine the concentration of CPF and 3,5,6- trichloropyridinol (TCP) in serum andthe activity of acetylcholinesterase (AChE) in cerebral cortex. Urine samples werecollectedon days 3,6 and 11,to determine the cumulative amount of TCP in urine. PBTK/TD model was usedto predict the time-concentration curve of the indexes. RESULTS:The concentrations of serum CPF and TCP first increased and then decreased with time every 24 h during the period of administration,significantly different with the control group (P<0.05). The activities of AChE inserum and cerebral cortex alsoshowedcyclical changes over time. The activities of AChE in cortex and serum both decreased as theCPFdose increased (P<0.05).The first day after exposurestopped,the activity of AChE in serum had a remarkable recovery (P<0.05).CONCLUSION:In repeated exposure,toxicokinetic and toxicodynamic indexes showed periodic variation. Continuous exposure to chlorpyrifos resulted in AChE in cortex and serum tobemaintained at a certain level of inhibition,which only recoveredwhen untilsignificantly exposure stopped.关键词
毒死蜱/PBTK/TD模型/重复经口暴露/毒代动力学/毒效应学Key words
chlorpyrifos/PBTK/TD model/repeated oral exposure/toxicokinetics/toxicodynamics分类
医药卫生引用本文复制引用
姚欣雅,赵敏娴,曹正颖,王灿楠..应用PBTK/TD模型研究毒死蜱经口重复染毒幼年大鼠的毒代动力学及毒效应学[J].癌变·畸变·突变,2015,(5):386-393,8.基金项目
国家自然科学基金(81273080，81072304) （81273080，81072304）
