Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei, Taiwan 10617, Republic of China,
Int J Nanomedicine. 2019 Mar 5;14:1687-1703. doi: 10.2147/IJN.S171510. eCollection 2019.
No systematic investigations have been conducted to assess the lung burden imposed by the chronic inhalation of silver nanoparticles (AgNPs) emitted by spray products.
The objective of this study was to formulate a study framework that integrates a probabilistic risk assessment scheme with a mechanistic lung burden model for the estimation of health risks associated with the long-term inhalation of AgNP-containing spray products.
A compartmentalized physiologically based alveolar deposition (PBAD) model was used to estimate AgNP lung burden. Dose-response relationships were established using nanotoxicity data sets obtained from rats (as a model organism). Weibull model-based thresholds of AgNP lung burden based on neutrophil-elevated inflammation bio-markers were estimated from Hill-based exposure-response relationships. Finally, the risks of lung disease posed by various AgNP-containing spray products were assessed.
Conservative thresholds for the prevention of pulmonary disease were estimated as follows (mean ± SE): 34 nm AgNPs (0.32±0.22 mg) and 60 nm AgNPs (1.08±0.64 mg). Our results indicate that the risk probability was 0.5 that the hazard quotient (HQ) estimates of deodorant with a count median diameter (CMD) ≈30 nm exceeded 1. The primary risk posed by AgNPs is transferred from the interstitial region to lymph nodes. Under the condition of 50% risk probability, the 97.5 percentile of HQ for the spray products were as follows: CMD ≈30 nm (3.4) and CMD ≈60 nm (~1.1).
Our application of the proposed risk assessment scheme to the results obtained in an in vivo animal model proved highly effective in elucidating the relationship between the characteristics of metallic NP-containing spray products and their corresponding toxicity. The integration of the proposed PBAD model with a risk assessment framework enables the rapid assessment of risk posed by spray products containing metallic NPs over various time scales.
目前尚无系统研究评估喷涂产品中银纳米粒子(AgNPs)慢性吸入对肺部的影响。
本研究旨在制定一个整合概率风险评估方案和机制性肺部负荷模型的框架,用于估算与长期吸入含 AgNP 喷雾产品相关的健康风险。
使用分区生理肺泡沉积(PBAD)模型来估算 AgNP 的肺部负荷。使用从大鼠(作为模型生物)获得的纳米毒性数据集建立剂量-反应关系。使用基于 Weibull 模型的基于生物标志物的中性粒细胞升高炎症的 AgNP 肺部负荷阈值,从基于 Hill 的暴露-反应关系中进行估算。最后,评估了各种含 AgNP 喷雾产品引起肺部疾病的风险。
保守的预防肺部疾病的阈值估计如下(平均值±SE):34nm AgNPs(0.32±0.22mg)和 60nm AgNPs(1.08±0.64mg)。我们的结果表明,风险概率约为 0.5,即除臭剂的危害商(HQ)估计值,其计数中位径(CMD)≈30nm 超过 1。AgNPs 造成的主要风险从间质区转移到淋巴结。在 50%风险概率的条件下,喷雾产品的 97.5%HQ 如下:CMD≈30nm(约 3.4)和 CMD≈60nm(约 1.1)。
我们将所提出的风险评估方案应用于体内动物模型的结果,证明了在阐明含金属 NP 喷雾产品的特性与其相应毒性之间的关系方面非常有效。将所提出的 PBAD 模型与风险评估框架相结合,可以快速评估各种时间尺度下含金属 NP 喷雾产品的风险。