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A Modified Parallel Artificial Membrane Permeability Assay for Evaluating the Bioconcentration of Highly Hydrophobic Chemicals in Fish

机译:改进的平行人工膜通透性测定方法,用于评估鱼类中高疏水性化学品的生物浓度

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Low cost in vitro tools are needed at the screening stage of assessment of bioaccumulation potential of new and existing chemicals because the number of chemical substances that needs to be tested highly exceeds the capacity of in vivo bioconcentration tests. Thus, the parallel artificial membrane permeability assay (PAMPA) system was modified to predict passive uptake/ elimination rate in fish. To overcome the difficulties associated with low aqueous solubility and high membrane affinity of highly hydrophobic chemicals, we measured the rate of permeation from the donor poly(dimethylsiloxane) (PDMS) disk to the acceptor PDMS disk through aqueous and PDMS membrane boundary layers and term the modified PAMPA system "PDMS-PAMPA". Twenty chemicals were selected for validation of PDMS-PAMPA. The measured permeability is proportional to the passive elimination rate constant in fish and was used to predict the "minimum" in vivo elimination rate constant. The in vivo data were very close to predicted values except for a few polar chemicals and metabolically active chemicals, such as pyrene and benzo[a]pyrene. Thus, PDMS-PAMPA can be an appropriate in vitro system for nonmetabolizable chemicals. Combination with metabolic clearance rates using a battery of metabolic degradation assays would enhance the applicability for metabolizable chemicals.
机译:在评估新化学品和现有化学品的生物蓄积潜力的筛选阶段,需要低成本的体外工具,因为需要测试的化学物质数量大大超过了体内生物浓缩测试的能力。因此,对平行人工膜通透性测定(PAMPA)系统进行了改进,以预测鱼类的被动摄取/消除率。为克服与高疏水性化学品的低水溶性和高膜亲和力相关的难题,我们测量了从供体聚二甲基硅氧烷(PDMS)膜通过水和PDMS膜边界层渗透至受体PDMS膜的速率,并将其称为修改后的PAMPA系统“ PDMS-PAMPA”。选择了20种化学物质用于PDMS-PAMPA的验证。所测得的渗透率与鱼类中的被动消除速率常数成比例,并用于预测“最小”体内消除速率常数。除少数极性化学物质和代谢活性化学物质(例如和苯并[a] py)外,体内数据与预测值非常接近。因此,PDMS-PAMPA可能是适用于不可代谢化学物质的体外系统。使用一系列代谢降解试验与代谢清除率相结合,将增强可代谢化学物质的适用性。

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  • 来源
    《Environmental Science & Technology》 |2008年第5期|1787-1793|共页
  • 作者单位
  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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  • 正文语种 eng
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