Process Engineering Group, Marine Research Institute IIM-CSIC, Eduardo Cabello 6, 36208 Vigo, Spain.
Chemosphere. 2010 Apr;79(4):377-86. doi: 10.1016/j.chemosphere.2010.02.010. Epub 2010 Mar 3.
In the present work, a set of generic parameters was proposed for a pharmacokinetic model, with the objective of predicting Cd concentration in the tissues of diverse fish species under different environmental conditions. Cd concentrations in a number of tissues of Oncorhynchus mykiss and Cyprinus carpio were estimated by a structurally identifiable multicompartmental model (unique solution). The 13 generic parameters of the model comprised exchange rates, tissue-blood partition coefficients, and weight-corrected elimination rate constants accounting for the routes of water respiration, excretion and egestion. On the other hand, absorption efficiencies from water and food were considered to be condition-specific and estimated for each experiment. These two parameters reflected the differences in fish exposure to diet (food type and metal concentration) or water (water chemistry and bioavailable metal concentration). A data set of 27 experiments of Cd bioaccumulation in fish tissues was compiled for model calibration. The selected dynamics on trout and carp were performed under very different experimental conditions, involving water and/or food exposure, different fish weights and exposure concentrations and the presence/absence of depuration periods. Model predicted, for most compartments and experiments, the tendency of Cd dynamics. However, accumulation in liver and kidney was underestimated in approximately a half of the experiments, due mainly to a rapid metallothionein (MT) sequestration phenomena and subsequent saturation on liver and kidney produced under high exposure concentrations. On the other hand, both generic and condition-specific parameter values were in accordance with the values reported in literature when available. Therefore, the results obtained in this work are an initial step indicating that a generic global input parameter set could be applied to physiology-based pharmacokinetic (PBPK) models for estimating Cd accumulation in fish in different types of scenarios.
在本工作中，提出了一组用于药代动力学模型的通用参数，旨在预测不同环境条件下不同鱼类物种组织中的 Cd 浓度。通过结构可识别的多室模型（唯一解）估计了 Oncorhynchus mykiss 和 Cyprinus carpio 多种组织中的 Cd 浓度。模型的 13 个通用参数包括交换率、组织-血液分配系数和重量校正消除率常数，这些参数可用于解释水呼吸、排泄和排遗的途径。另一方面，从水和食物中的吸收效率被认为是特定于条件的，并为每个实验进行了估计。这两个参数反映了鱼类暴露于饮食（食物类型和金属浓度）或水（水化学和生物可利用金属浓度）的差异。为模型校准编制了一个包含 27 个鱼类组织 Cd 生物累积实验的数据组。选择的鳟鱼和鲤鱼动力学在非常不同的实验条件下进行，涉及水和/或食物暴露、不同的鱼类体重和暴露浓度以及是否存在或不存在净化期。模型预测了大多数隔室和实验中 Cd 动力学的趋势。然而，由于暴露浓度高时肝脏和肾脏中金属硫蛋白 (MT) 快速隔离和随后饱和的现象，大约一半的实验中肝脏和肾脏中的积累被低估了。另一方面，通用和特定条件的参数值与文献中报道的值相符。因此，本工作的结果是一个初步步骤，表明通用的全局输入参数集可应用于基于生理学的药代动力学 (PBPK) 模型，以估计不同类型情景下鱼类中的 Cd 积累。
