Abbas R, Schultz I R, Doddapaneni S, Hayton W L
Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, Ohio State University, Columbus 43210, USA.
Toxicol Appl Pharmacol. 1996 Jan;136(1):194-9. doi: 10.1006/taap.1996.0024.
Fish are less sensitive than mammals to organophosphate insecticide toxicity. The species differences have been mainly investigated by biochemical studies of AChE and organophosphate interaction. To examine whether species differences in the toxicokinetics of the organophosphate insecticides were also involved in their differential toxicity, rainbow trout were fitted with a dorsal aorta cannula and administered parathion and its active metabolite paraoxon intraarterially (ia) and via water exposure. Serial blood samples were removed and the plasma concentrations of parathion and paraoxon were determined by capillary GC with EC detection. Plasma protein binding was determined by equilibrium dialysis and ultrafiltration. After ia injection the plasma concentration-time profiles of parathion and paraoxon were multiexponential, with a terminal t1/2 of 56.1 and 0.528 hr. The steady-state volumes of distribution and total body clearances (CLb) for parathion and paraoxon were 1370 and 1080 ml kg-1 and 21.4 and 3020 ml hr-1 kg-1; the plasma unbound fractions were 1.23 and 52.5%. The large difference in CLb between parathion and paraoxon appeared to result primarily from differences in plasma protein binding. Parathion had greater persistence in trout than rat, suggesting that sensitivity difference were unrelated to toxicokinetic differences.
鱼类对有机磷酸酯类杀虫剂毒性的敏感性低于哺乳动物。物种差异主要通过对乙酰胆碱酯酶(AChE)与有机磷酸酯相互作用的生化研究来探究。为了检验有机磷酸酯类杀虫剂的毒代动力学方面的物种差异是否也与其不同的毒性有关,给虹鳟鱼安装了背主动脉插管,并通过动脉内(ia)注射和水暴露的方式给予其对硫磷及其活性代谢产物对氧磷。采集系列血样,采用带电子捕获检测的毛细管气相色谱法测定血浆中对硫磷和对氧磷的浓度。通过平衡透析和超滤法测定血浆蛋白结合情况。动脉内注射后,对硫磷和对氧磷的血浆浓度-时间曲线呈多指数形式,终末半衰期分别为56.1小时和0.528小时。对硫磷和对氧磷的稳态分布容积和总体清除率(CLb)分别为1370和1080 ml·kg-1以及21.4和3020 ml·hr-1·kg-1;血浆未结合分数分别为1.23%和52.5%。对硫磷和对氧磷在CLb上的巨大差异似乎主要源于血浆蛋白结合的差异。对硫磷在鳟鱼体内的存留时间比在大鼠体内更长,这表明敏感性差异与毒代动力学差异无关。