首页> 外文OA文献 >Assessing the reliability of uptake and elimination kinetics modelling approaches for estimating bioconcentration factors in the freshwater invertebrate, Gammarus pulex Thomas H. Miller, Gillian L. McEneff, Lucy C. Stott, Stewart F. Owen, Nicolas R. Bury, Leon P. Barron
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Assessing the reliability of uptake and elimination kinetics modelling approaches for estimating bioconcentration factors in the freshwater invertebrate, Gammarus pulex Thomas H. Miller, Gillian L. McEneff, Lucy C. Stott, Stewart F. Owen, Nicolas R. Bury, Leon P. Barron

机译:评估摄取和消除动力学建模方法的可靠性,以评估淡水无脊椎动物中的生物富集因子,伽马鲁斯·普雷克斯·托马斯·H·米勒,吉莉安·L·麦肯内夫,露西·C·斯托特,斯图尔特·F·欧文,尼古拉斯·R·伯里,莱昂·P·巴伦

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摘要

This study considers whether the current standard toxicokinetic methods are an accurate and applicable assessment of xenobiotic exposure in an aquatic freshwater invertebrate. An in vivo exposure examined the uptake and elimination kinetics for eight pharmaceutical compounds in the amphipod crustacean, Gammarus pulex by measuring their concentrations in both biological material and in the exposure medium over a 96 h period. Selected pharmaceuticals included two anti-inflammatories (diclofenac and ibuprofen), two beta-blockers (propranolol and metoprolol), an anti-depressant (imipramine), an anti-histamine (ranitidine) and two beta-agonists (formoterol and terbutaline). Kinetic bioconcentration factors (BCFs) for the selected pharmaceuticals were derived from a first-order one-compartment model using either the simultaneous or sequential modelling methods. Using the simultaneous method for parameter estimation, BCF values ranged from 12 to 212. In contrast, the sequential method for parameter estimation resulted in bioconcentration factors ranging from 19 to 4533. Observed toxicokinetic plots showed statistically significant lack-of-fits and further interrogation of the models revealed a decreasing trend in the uptake rate constant over time for rantidine, diclofenac, imipramine, metoprolol, formoterol and terbutaline. Previous published toxicokinetic data for 14 organic micro-pollutants were also assessed and similar trends were identified to those observed in this study. The decreasing trend of the uptake rate constant over time highlights the need to interpret modelled data more comprehensively to ensure uncertainties associated with uptake and elimination parameters for determining bioconcentration factors are minimised.
机译:这项研究考虑了当前的标准毒物动力学方法是否是对水生淡水无脊椎动物中异源生物暴露的准确和适用的评估。体内暴露通过测量96小时内两栖类甲壳类动物,γ短小G虫中八种药物在生物材料和暴露介质中的浓度来研究其吸收和消除动力学。选定的药物包括两种抗炎药(双氯芬酸和布洛芬),两种β-受体阻滞剂(普萘洛尔和美托洛尔),抗抑郁药(丙咪嗪),抗组胺药(雷尼替丁)和两种β-激动剂(福莫特罗和特布他林)。所选药物的动力学生物富集因子(BCF)是使用同时建模或顺序建模方法从一阶单室模型得出的。使用同时进行参数估计的方法,BCF值在12到212之间。相反,在连续进行参数估计的方法中,生物富集系数在19到4533之间。观察到的毒代动力学曲线在统计上显着地缺乏拟合,并且进一步询问这些模型显示出随着时间的推移,异丁啶,双氯芬酸,丙咪嗪,美托洛尔,福莫特罗和特布他林的吸收速率常数呈下降趋势。还评估了先前发布的14种有机微污染物的毒物动力学数据,并确定了与本研究中观察到的趋势相似的趋势。吸收速率常数随时间下降的趋势表明,需要更全面地解释建模数据,以确保将与用于确定生物富集因子的吸收和消除参数相关的不确定性降至最低。

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