典型污染区室内灰尘中铅砷人体生物有效性预测模型的构建与应用

China is undergoing rapid urbanization and industrialization which give rise to lead (Pb) and arsenic (As) pollution in house dusts. Incidental ingestion of Pb and As contaminated house dust is a great threat to human health. Reliable estimates of Pb and As exposure via incidental dust ingestion depend on accurate quantification of the Pb and As fraction in house dust that can be absorbed into the systemic circulation, i.e., bioavailability. In vivo bioavailability studies using different animal models (e.g., swine and mouse) are time required, expensive, therefore not suitable for site-specific assessment. There is a great need to develop bioavailability predictive models for contaminated house dust by establishing linear relationships between in vivo and in vitro assays which are simple, rapid, and inexpensive. In the proposal, we will focus on house dusts contaminated with Pb and As via a number of different sources from China and aim to develop bioavailability predictive models and use them in human health risk assessment. We will use synchrotron radiation X ray absorption technique to examine Pb and As speciation in house dusts contaminated from different sources and investigate their influence on Pb and As bioavailability. Then, we will choose representive samples with different Pb and As speciation to develop bioavailability predictive models by establishing linear relationships between in vivo mouse and in vitro assays. Furthermore, we will validate the constructed predictive models through the assessment of an independent data set using the same mouse assay and in vitro assays and a number of cross validation methods. The predictive models will be used to predict Pb and As bioavailability from bioaccessibility data derived from in vitro assays. Human health risk of exposure to Pb and As via incidental ingestion of house dusts contaminated from different sources from China will be assessed based on Pb and As bioavailability.

随着我国城市化和工业化的加快，室内灰尘铅砷污染日益严重，对人体健康造成重大危害。准确测定室内灰尘中铅砷的生物有效性成为其人体健康风险评价的重要理论依据。然而，目前测定生物有效性的动物活体实验费用高、耗时、不能满足大批量样品的测试需求。本项目以我国不同污染源室内灰尘为研究对象，以基于体外试验的生物有效性预测模型的构建及应用为研究目标。利用同步辐射X射线吸收技术表征不同污染源室内灰尘中铅砷的形态分布特征，揭示形态对其生物有效性的影响机制。选取不同铅砷形态的代表性样品，通过小鼠实验和体外胃肠液试验对比，建立两者间的线性相关性，确定体外试验方法在预测室内灰尘中铅砷生物有效性的适用性，构建基于体外试验的生物有效性预测模型，并采取多种交叉验证方法，验证建立模型的准确性。通过生物有效性模型的构建，综合评价典型污染区内室内灰尘中铅砷的人体健康风险，为我国室内灰尘中重金属健康风险评价提供理论依据和技术支持。

随着我国城市化和工业化的加快，室内灰尘铅砷污染日益严重，对人体健康造成重大危害 。准确测定室内灰尘中铅砷的生物有效性成为其人体健康风险评价的重要理论依据。然而，目前测定生物有效性的动物活体实验费用高、耗时、不能满足大批量样品的测试需求。本研究以我国湖南铅锌矿区室内灰尘为研究对象，通过建立小鼠活体试验和体外胃肠模拟液方法，测试了污染区室内灰尘样品中砷、铅和镉的相对生物有效性，揭示了污染来源和重金属存在形态对重金属生物有效性的影响；对比活体实验与体外试验，建立两者之间的线性相关性，构建生物有效性预测模型；基于生物有效性，评估了污染区室内灰尘的人体健康风险。取得主要结论如下：（1）不同动物模型、不同暴露方式以及选取不同生物靶器官测定的砷相对生物有效性间整体上差异较小，表明操作相对简便、花费较低的小鼠活体实验方法可以替代幼猪实验；（2）利用小鼠活体试验方法，本研究测定了我国湖南铅锌矿区室内灰尘样品中砷、铅和镉的相对生物有效性，发现不同样品间存在较大差异，砷、铅和镉的相对生物有效性的变异范围为8.49–37.0%、7.21–52.1%和20.3–94.3%；（3）与非污染矿区样品相比，锌矿区室内灰尘样品中砷和铅的相对生物有效性显著较低，表明重金属污染来源和存在形态显著影响其人体生物有效性；（4）建立了小鼠活体试验与体外胃肠模拟液之间的线性相关关系，即生物有效性预测模型，揭示了能够预测矿区污染室内灰尘样品中重金属人体生物有效性的最佳体外方法，发现PBET肠液提取和UBM肠液提取是测试砷生物有效性的合适体外方法；PBET方法是试镉生物有效性的合适体外方法；而UBM胃液提取方法是测试铅生物有效性的合适体外方法；（5）基于生物有效性和铅稳定同位素源解析，本研究评估了室内灰尘摄入产生的人体健康风险，发现对于成人，大米摄入是砷暴露的主要途径，然而对于儿童，室内灰尘反而是砷暴露的主要途径；不论成人或儿童，大米摄入是镉暴露主要途径，而室内灰尘摄入是人体铅暴露的最主要途径。