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目的 :测定一次性经口暴露毒死蜱(chlorpyrifos,CPF)的毒物代谢动力学和毒效学指标,研究CPF的毒代动力学和毒效学特征。方法:雌性SD大鼠按体质量随机分为4个剂量组和1个阴性对照组,每组15只。剂量分组为:12.5、25.0、50.0、100.0 mg/kg,一次性灌胃染毒。染毒后1、3、6、12和24 h 5个时间点分别在每个剂量组随机选择3只大鼠,乙醚麻醉,股动脉取血,颈椎脱臼处死,分离大脑皮质,用高效液相色谱法测定这5个时间点的血清中CPF和3,5,6-三氯-2-吡啶(3,5,6-trichloropyridinol,TCP)的浓度,用胆碱酯酶试剂盒测定血清和大脑皮质中乙酰胆碱酯酶(acetylcholinesterase,AChE)活性。结果:血清CPF和TCP的浓度随时间变化,先上升后下降,前者峰值浓度出现在染毒后3 h,后者为6 h左右;血清和皮质的AChE活性随时间变化,先下降后上升,血清AChE活性在染毒后3~6 h抑制程度最大,皮质AChE在染毒后6~12 h抑制程度最大。血清CPF浓度、TCP浓度与AChE活性均成线性负相关,血清CPF浓度与TCP浓度呈线性正相关。结论:获得了毒死蜱经口暴露的多项毒代动力学和毒效学数据,阐明了毒代动力学和毒效学特征,为毒死蜱生理毒物代谢动力学和毒物效应动力学模型的建立和完善提供了科学依据。
OBJECTIVE: To determine the toxicokinetics and toxicokinetic parameters of chlorpyrifos (CPF) after one-time oral exposure and to study the toxicokinetic and toxicological characteristics of CPF. Methods: Female SD rats were randomly divided into 4 dose groups and 1 negative control group, with 15 rats in each group. Dose groups were: 12.5, 25.0, 50.0, 100.0 mg / kg, a one-time intragastric administration. Three rats were randomly selected in each dose group at 1, 3, 6, 12 and 24 h after injection. Ether was anesthetized, blood was taken from the femoral artery, the cervical dislocation was sacrificed, and the cerebral cortex was isolated. The concentration of CPF and 3,5,6-trichloropyridinol (TCP) in the serum at these 5 time points were measured by chromatography. Serum and brain were measured using a cholinesterase kit Cortical acetylcholinesterase (acetylcholinesterase, AChE) activity. Results: The concentrations of serum CPF and TCP changed first and then decreased. The former peaked at 3 h and the latter at 6 h. The activity of AChE in serum and cortex changed with time and then decreased and then increased. The activity of AChE in serum was most inhibited 3 ~ 6 h after exposure, and the inhibition of AChE in cortex was the highest at 6 ~ 12 h after exposure. Serum CPF concentration, TCP concentration and AChE activity were linearly negative correlation, serum CPF concentration and the concentration of TCP showed a positive linear correlation. CONCLUSIONS: A number of toxicokinetic and toxicodynamic data were obtained for oral exposure of chlorpyrifos. The pharmacokinetic and toxicological characteristics of chlorpyrifos were also elucidated. The kinetic and toxicokinetic models of chlorpyrifos were established and perfected Provide a scientific basis.