Translating nanoparticle dosimetry from conventional in vitro systems to occupational inhalation exposures.
Translating nanoparticle dosimetry from conventional in vitro systems to occupational inhalation exposures.
复制标题
将纳米颗粒剂量测定从传统的体外系统转化为职业性吸入暴露。
DOI：
10.1016/j.jaerosci.2021.105771
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发表时间：
2021-06
影响因子：
4.5
通讯作者：
Skinner, Andrew W.
中科院分区：
文献类型：
--
作者：
Smith, Jordan Ned;Skinner, Andrew W.
在21世纪毒性测试的鼓舞下，研究人员越来越多地应用高通量体外方法来识别和表征纳米颗粒的危害，包括传统的水细胞培养系统来评估呼吸危害。将纳米颗粒剂量从传统的毒性测试系统转换为相关的人体暴露仍然是评估纳米颗粒暴露的职业风险的主要挑战。在这里，我们探索了现有的计算工具和数据，可用于将纳米粒子剂量度量从细胞测试系统转换为人体中纳米银的吸入暴露。我们使用多路径粒子剂量学(MPPD)模型预测了暴露于20 nm和110 nm银纳米粒子的人体在8小时内的纳米粒子沉积，剂量为0.9μg/m~3，这是美国国家职业安全与健康研究所建议的暴露限值(REL)。MPPD预测，20 nm和110 nm纳米粒子在8 h内分别沉积了8.1和3.7μg的银，其中20 nm粒子的总比表面积增加了近11倍。由于肺内液体积的区域差异，与肿块沉积模式(第4代与第20-21代)相比，沉积纳米颗粒的峰值浓度出现在肺内更近的地方。假设以前研究中测量的纳米粒子质量分数为0.4%，则预测20 nm和110 nm粒子的细胞内银离子的峰值浓度分别为1.0 6和0.89μg/mL。这两种预测的浓度都低于体外评估所测得的细胞内银离子毒性阈值1.7mgg/ml。假设4%的质量溶解预测组织中的银浓度会高出10倍，20和110 nm纳米颗粒的峰值分别为10.6和8.9μg/mL，超过了体外观察到的毒性阈值，并突显了溶出率的重要性和敏感性。总体而言，这种方法提供了一个框架，用于推断体外细胞培养系统对人体暴露的纳米毒性结果。将来自体外和体内危险特征的适当剂量度量与来自职业暴露的人类肺部剂量相一致，是成功的纳米颗粒风险评估和工人保护的关键组成部分，为设计未来针对相关人类暴露的体外研究提供指导。
As encouraged by Toxicity Testing in the 21st Century, researchers increasingly apply high-throughput in vitro approaches to identify and characterize nanoparticle hazards, including conventional aqueous cell culture systems to assess respiratory hazards. Translating nanoparticle dose from conventional toxicity testing systems to relevant human exposures remains a major challenge for assessing occupational risk of nanoparticle exposures. Here, we explored existing computational tools and data available to translate nanoparticle dose metrics from cellular test systems to inhalation exposures of silver nanoparticles in humans. We used the Multiple-Path Particle Dosimetry (MPPD) Model to predict nanoparticle deposition of humans exposed to 20 and 110 nm silver nanoparticles at 0.9 μg/m3 over an 8 h period, the proposed National Institute of Occupational Safety and Health (NIOSH) recommended exposure limit (REL). MPPD predicts 8.1 and 3.7 μg of silver deposited in an 8 h period for 20 and 110 nm nanoparticles, respectively, with 20 nm particles displaying nearly 11-fold higher total surface area deposited. Peak deposited nanoparticle concentrations occurred more proximal in the pulmonary tract compared to mass deposition patterns (generation 4 vs. generations 20–21, respectively) due to regional differences in lung lining fluid volumes. Assuming 0.4% nanoparticle dissolution by mass measured in previous studies predicted peak concentrations of silver ions in cells of 1.06 and 0.89 μg/mL for 20 and 110 nm particles, respectively. Both predicted concentrations are below the measured toxic threshold of 1.7 μg/mL of silver ions in cells from in vitro assessments. Assuming 4% dissolution by mass predicted 10-fold higher silver concentrations in tissues, peaking at 10.6 and 8.9 μg/mL, for 20 and 110 nm nanoparticles respectively, exceeding the observed in vitro toxic threshold and highlighting the importance and sensitivity of dissolution rates. Overall, this approach offers a framework for extrapolating nanotoxicity results from in vitro cell culture systems to human exposures. Aligning appropriate dose metrics from in vitro and in vivo hazard characterizations and human pulmonary doses from occupational exposures are critical components for successful nanoparticle risk assessment and worker protection providing guidance for designing future in vitro studies aimed at relevant human exposures.
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影响因子：
10
作者：
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5.6
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Salar-Behzadi S