CAJ | 학술논문

目的：应用PBTK/TD模型研究幼年大鼠经口重复暴露毒死蜱(CPF)的毒代动力学及毒效应学。方法：21日龄雌性SD大鼠按体质量随机分成对照组、1.0、2.5、5.0、10.0和15.0 mg/kg毒死蜱剂量组，每天1次，连续灌胃10 d，在第3、6、10和11天收集血清和大脑皮质，测定血清CPF和3，5，6-三氯-2-吡啶(TCP)浓度、血清和皮质的乙酰胆碱酯酶活力(AChE)活力；收集第3、6和11天的尿液，测定尿液TCP累积量。在幼年大鼠毒死蜱经口暴露PBTK/TD模型中输入暴露条件，模拟各个指标的时量变化曲线。结果：以24 h为1个周期，每次染毒后血清CPF和TCP浓度随时间的增加先上升后下降，与对照组间的差异具有统计学意义(P<0.05)。血清和皮质AChE活力随时间亦呈周期性变化，均随着染毒剂量的增加而减小，具有统计学意义( P<0.05)；而在停止染毒后第1天，血清AChE活力显著恢复，具有统计学意义(P<0.05)。结论：毒死蜱在重复染毒时，毒代谢动力学与毒效应学指标均呈周期性变化，其持续暴露会使血清和大脑皮质AChE维持在一定的抑制水平，停止暴露后可显著恢复。
목적：응용PBTK/TD모형연구유년대서경구중복폭로독사비(CPF)적독대동역학급독효응학。방법：21일령자성SD대서안체질량수궤분성대조조、1.0、2.5、5.0、10.0화15.0 mg/kg독사비제량조，매천1차，련속관위10 d，재제3、6、10화11천수집혈청화대뇌피질，측정혈청CPF화3，5，6-삼록-2-필정(TCP)농도、혈청화피질적을선담감지매활력(AChE)활력；수집제3、6화11천적뇨액，측정뇨액TCP루적량。재유년대서독사비경구폭로PBTK/TD모형중수입폭로조건，모의각개지표적시량변화곡선。결과：이24 h위1개주기，매차염독후혈청CPF화TCP농도수시간적증가선상승후하강，여대조조간적차이구유통계학의의(P<0.05)。혈청화피질AChE활력수시간역정주기성변화，균수착염독제량적증가이감소，구유통계학의의( P<0.05)；이재정지염독후제1천，혈청AChE활력현저회복，구유통계학의의(P<0.05)。결론：독사비재중복염독시，독대사동역학여독효응학지표균정주기성변화，기지속폭로회사혈청화대뇌피질AChE유지재일정적억제수평，정지폭로후가현저회복。
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.