Department of Mechanical Engineering, Hanyang University, Ansan, South Korea.
Aerosol Toxicology Research Center, HCTm CO.,LTD, Icheon, South Korea.
Part Fibre Toxicol. 2021 Jan 21;18(1):5. doi: 10.1186/s12989-021-00397-z.
Inhalation exposure to nanomaterials in workplaces can include a mixture of multiple nanoparticles. Such ambient nanoparticles can be of high dissolution or low dissolution in vivo and we wished to determine whether co-exposure to particles with different dissolution rates affects their biokinetics.
Rats were exposed to biosoluble silver nanoparticles (AgNPs, 10.86 nm) and to biopersistent gold nanoparticles (AuNPs, 10.82 nm) for 28 days (6-h/day, 5-days/week for 4 weeks) either with separate NP inhalation exposures or with combined co-exposure. The separate NPs mass concentrations estimated by the differential mobility analyzer system (DMAS) were determined to be 17.68 ± 1.69 μg/m for AuNP and 10.12 ± 0.71 μg/m for AgNP. In addition, mass concentrations analyzed by atomic absorption spectrometer (AAS) via filter sampling were for AuNP 19.34 ± 2.55 μg/m and AgNP 17.38 ± 1.88 μg/m for separate exposure and AuNP 8.20 ± 1.05 μg/m and AgNP 8.99 ± 1.77 μg/m for co-exposure. Lung retention and clearance were determined on day 1 (6-h) of exposure (E-1) and on post-exposure days 1, 7, and 28 (PEO-1, PEO-7, and PEO-28, respectively). While the AgNP and AuNP deposition rates were determined to be similar due to the similarity of NP size of both aerosols, the retention half-times and clearance rates differed due to the difference in dissolution rates. Thus, when comparing the lung burdens following separate exposures, the AgNP retention was 10 times less than the AuNP retention at 6-h (E-1), and 69, 89, and 121 times lower less than the AuNP retention at PEO-1, PEO-7, and PEO-28, respectively. In the case of AuNP+AgNP co-exposure, the retained AgNP lung burden was 14 times less than the retained AuNP lung burden at E-1, and 26, 43, and 55 times less than the retained AuNP lung burden at PEO-1, PEO-7, and PEO-28, respectively. The retention of AuNP was not affected by the presence of AgNP, but AgNP retention was influenced in the presence of AuNP starting at 24 h after the first day of post day of exposure. The clearance of AgNPs of the separate exposure showed 2 phases; fast (T 3.1 days) and slow (T 48.5 days), while the clearance of AuNPs only showed one phase (T .81.5 days). For the co-exposure of AuNPs+AgNPs, the clearance of AgNPs also showed 2 phases; fast (T 2.2 days) and slow (T 28.4 days), while the clearance of AuNPs consistently showed one phase (T 54.2 days). The percentage of Ag lung burden in the fast and slow clearing lung compartment was different between separate and combined exposure. For the combined exposure, the slow and fast compartments were each 50% of the lung burden. For the single exposure, 1/3 of the lung burden was cleared by the fast rate and 2/3 of the lung burden by the slow rate.
The clearance of AgNPs follows a two- phase model of fast and slow dissolution rates while the clearance of AuNPs could be described by a one- phase model with a longer half-time. The co-exposure of AuNPs+AgNPs showed that the clearance of AgNPs was altered by the presence of AuNPs perhaps due to some interaction between AgNP and AuNP affecting dissolution and/or mechanical clearance of AgNP in vivo.
在工作场所中，吸入纳米材料的暴露可能包括多种纳米颗粒的混合物。这种环境纳米颗粒在体内的溶解率可能很高，也可能很低，我们希望确定不同溶解速率的颗粒共同暴露是否会影响它们的生物动力学。
将生物可溶性银纳米颗粒（AgNPs，10.86nm）和生物持久性金纳米颗粒（AuNPs，10.82nm）分别以单独的 NP 吸入暴露或联合共暴露的方式，让大鼠暴露 28 天（每天 6 小时，每周 5 天，共 4 周）。通过差分迁移率分析仪系统（DMAS）估计的单独 NPs 质量浓度被确定为 AuNP 为 17.68±1.69μg/m，AgNP 为 10.12±0.71μg/m。此外，通过原子吸收光谱仪（AAS）通过滤膜采样分析的质量浓度为 AuNP 为 19.34±2.55μg/m，AgNP 为 17.38±1.88μg/m，单独暴露为 AuNP 为 8.20±1.05μg/m，AgNP 为 8.99±1.77μg/m，联合暴露为 AuNP 为 8.20±1.05μg/m，AgNP 为 8.99±1.77μg/m。在暴露（E-1）的第 1 天（6 小时）和暴露后第 1、7 和 28 天（PEO-1、PEO-7 和 PEO-28），分别测定肺保留和清除率。虽然由于两种气溶胶的 NP 尺寸相似，AgNP 和 AuNP 的沉积速率被确定为相似，但由于溶解速率的差异，保留半衰期和清除率不同。因此，在比较单独暴露后的肺负担时，AgNP 的保留量在 6 小时（E-1）时比 AuNP 的保留量少 10 倍，而在 PEO-1、PEO-7 和 PEO-28 时分别比 AuNP 的保留量少 69、89 和 121 倍。在 AuNP+AgNP 联合暴露的情况下，AgNP 在 E-1 时的肺保留量比 AuNP 的肺保留量少 14 倍，而在 PEO-1、PEO-7 和 PEO-28 时分别比 AuNP 的肺保留量少 26、43 和 55 倍。AuNP 的保留量不受 AgNP 的影响，但 AgNP 的保留量在接触后的第 1 天开始受到 AuNP 的影响。AgNPs 的单独暴露的清除显示出 2 个阶段；快速（T 3.1 天）和缓慢（T 48.5 天），而 AuNPs 的清除仅显示一个阶段（T.81.5 天）。对于 AuNPs+AgNPs 的联合暴露，AgNPs 的清除也显示出 2 个阶段；快速（T 2.2 天）和缓慢（T 28.4 天），而 AuNPs 的清除一直显示出一个阶段（T 54.2 天）。快速和缓慢清除肺隔室中 Ag 肺负担的百分比在单独和联合暴露之间有所不同。对于联合暴露，慢和快隔室各占肺负担的 50%。对于单一暴露，1/3 的肺负担通过快速速率清除，2/3 的肺负担通过缓慢速率清除。
AgNPs 的清除遵循快速和缓慢溶解速率的两阶段模型，而 AuNPs 的清除可以用半衰期较长的一阶段模型来描述。AuNPs+AgNPs 的联合暴露表明，AgNPs 的清除可能受到 AuNPs 的影响，这可能是由于 AgNP 和 AuNP 之间的一些相互作用影响了 AgNP 在体内的溶解和/或机械清除。
