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双酚A的生理毒代动力学(PBTK)模型构建研究
Construction of the Physiological Toxicokinetic Model of Bisphenol A

DOI: 10.12677/HJFNS.2021.103021, PP. 175-189

Keywords: 双酚A，生理毒代动力学模型，健康风险评估，人群
Bisphenol A, Physiologically Based Toxi-cokinetics, PBTK, Health Risk Assessment, Human

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Abstract:

双酚A (BPA)作为一种高产量的化学品，用于许多消费产品，如聚碳酸酯塑料、环氧树脂和热敏纸等。由于BPA的普遍存在性，与BPA接触相关的潜在影响，以及人类血清中异常高的BPA水平，一直是围绕BPA安全性争论的焦点，更好地解决这些争议的一个重要因素是描述BPA在人体中的药代动力学行为的基础过程。基于生理的药代动力学(PBPK)模型，将生理和生化信息整合到一个机制框架中，已广泛用于人类健康风险评估，定量描述化学物质及其代谢产物在人体中的药代动力学。本研究旨在既往研究基础上结合最新的毒理学研究结果，对模型结构进行了优化，主要体现在：a) 补充小肠的动脉血供、实现小肠的血液循环；b) 补充肾脏隔室；c) 去除肠肝循环过程。以产生毒性效应的非结合型BPA为指标，结果显示：优化后模型能更好地模拟人体膳食摄入BPA后血浆中非结合型BPA的浓度变化趋势。模型预测结果与实测值相近，优于既往研究结果，拟合效果良好。通过更新模型结构、优化模型参数和评价模型预测能力与可靠性等，拟建立一个汉族成年人(>18岁)经口摄入BPA的PBTK模型，实现膳食摄入场景下定量预测血液中BPA主要存在形式(未结合态BPA、BPAG和BPAS)的浓度–时间曲线，以及尿液中总BPA的浓度–时间曲线。该模型可为BPA暴露的健康风险评估提供技术支撑。
As a high yield chemical, bisphenol A (BPA) is used in many consumer products, such as polycarbonate plastics, epoxy resins, and thermal paper. Due to the prevalence of BPA, the potential effects associated with BPA exposure, and the abnormally high levels of BPA in human serum, have been the focus of debate surrounding the safety of BPA. An important factor in better resolving these controversies is to describe the underlying processes of the pharmacokinetic behavior of BPA in humans physiology-based pharmacokinetics (PBPK) models, which integrate physiological and biochemical information into a mechanistic framework, have been widely used in human health risk assessment to quantitatively describe the pharmacokinetics of chemicals and their metabolites in the human body. Based on previous studies and combined with the latest results of toxicological studies, this study optimized the structure of the model, which was mainly reflected in the following aspects: a) replenish the arterial blood supply of small intestine to achieve blood circulation of small intestine; b) supplement of renal compartment; c) the removal of enterohepatic circulation was based on unbound BPA, which had toxic effects, and the results showed that the optimized model could better simulate the trend of plasma unbound BPA concentration after dietary BPA intake. The predicted results of the model are close to the measured values, which is better than the previous research results. The fitting effect is good By updating the model structure, optimizing the model parameters and evaluating the prediction ability and reliability of the model, a Han adult (>18 years old) to quantitatively predict the time-concentration curves of the major forms of BPA (unbound BPA, BPAG and BPAS) in blood and total BPA in urine under dietary intake scenarios. This model can provide technical support

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