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A RESIDUE-BASED TOXICOKINETIC MODEL FOR PULSE-EXPOSURE TOXICITY IN AQUATIC SYSTEMS

机译:基于残基的水生系统脉冲暴露毒性的毒物动力学模型

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This pulse-exposure model (PULSETOX) is based on the simple one-compartment first-order kinetics (1CFOK) equation. It tracks the accumulation of waterborne organic chemicals by fish and predicts acute toxicity by means of previously established relationships between whole-body residues and lethality. The predictive capabilities of the model were tested with a data set of 27 acute pulse-exposure lethality tests with larval fathead minnows (Pimephales promelas) exposed to pentachloro-phenol (PCP). Tests included eight single exposures (2 to 96 h) and 19 multiple exposures, which varied in the number (2 to 15) and duration (2 to 24 h) of pulses, and time interval between pulses (6 to 24 h). Experimental work included determination of 1CFOK kinetics parameters from [~(14)C]PCP uptake and clearance, and from time-toxicity curves. Lethality was expected in any exposure regime where the fish reaches or exceeds the critical body residue (CBR) of 0.30 mmol PCP/kg fish (SD, ±0.02; n = 11). Using the CBR endpoint, the model accounted for between 90 and 93% of variability in the observed lethality data, depending on the toxicokinetic parameters employed. Predictive power of the model was optimized by using kinetics parameters derived from the toxicity curve for pulse-toxicity tests as shown by the regression: predicted LC50 = 1.04 • (observed LC50) + 0.01 (p < 0.001, r~2 = 0.94, n = 27).
机译:该脉冲暴露模型(PULSETOX)基于简单的单室一阶动力学(1CFOK)方程。它可以追踪鱼类中水生有机化学物质的积累,并通过预先确定的全身残留量和致死性之间的关系来预测急性毒性。该模型的预测能力用27个急性脉冲暴露致死性测试数据集进行了测试,其中幼虫黑头head鱼(Pimephales promelas)暴露于五氯苯酚(PCP)。测试包括八次单次曝光(2到96小时)和19次多次曝光,其脉冲数(2到15)和持续时间(2到24小时)以及两次脉冲之间的时间间隔(6到24小时)有所不同。实验工作包括从[〜(14)C] PCP的摄取和清除以及时间-毒性曲线确定1CFOK动力学参数。在任何暴露条件下,如果鱼达到或超过0.30 mmol PCP / kg鱼的临界身体残留量(CBR)(SD,±0.02; n = 11),都有望达到致死性。使用CBR终点,该模型占观察到的致死率数据变异性的90%至93%,这取决于所采用的毒物动力学参数。通过使用从毒性曲线得出的动力学参数对脉冲毒性试验优化动力学模型,如回归所示,优化了模型的预测能力:预测的LC50 = 1.04•(观察到的LC50)+ 0.01(p <0.001,r〜2 = 0.94,n = 27)。

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