Katsnelson Boris A, Sutunkova Marina P, Konysheva Ludmila K, Solovyeva Svetlana N, Minigalieva Ilzira A, Gurvich Vladimir B, Privalova Larissa I
The Ekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers of the Rospotrebnadzor, Ekaterinburg, Russia.
Toxicol Rep. 2019 Mar 27;6:279-287. doi: 10.1016/j.toxrep.2019.03.008. eCollection 2019.
The paper retraces the development of a mechanistic multicompartmental system model describing particle retention in lungs under chronic inhalation exposures. This model was first developed and experimentally tested for various conditions of exposure to polydisperse dusts of SiO or TiO. Later on it was successfully used as a basis for analyzing patterns in the retention of nanoparticles having different chemical compositions (FeO, SiO, NiO). This is the first publication presenting the outcomes of modeling lung retention of nickel oxide nano-aerosols under chronic inhalation exposure. The most significant adaptation of the above-mentioned model to the conditions of exposure to metal-oxide nanoparticles is associated with the need to describe mathematically not only the physiological mechanisms of their elimination but also their solubilization "in vivo" bearing in mind that the relative contribution of the latter may be different for nanoparticles of different nature and predominant in some cases. Using nickel oxide as an example, it is suggested as well that damage to the physiological pulmonary clearance mechanisms by particularly toxic nanoparticles may result in lung toxicokinetics becoming nonlinear.
本文追溯了一个描述慢性吸入暴露下肺部颗粒滞留的多隔室机制系统模型的发展历程。该模型最初是针对二氧化硅或二氧化钛多分散粉尘的各种暴露条件开发并进行实验测试的。后来，它成功地被用作分析具有不同化学成分（氧化亚铁、二氧化硅、氧化镍）的纳米颗粒滞留模式的基础。这是第一篇展示慢性吸入暴露下氧化镍纳米气溶胶肺部滞留建模结果的出版物。上述模型针对金属氧化物纳米颗粒暴露条件的最显著调整，与不仅要从数学上描述其消除的生理机制，还要考虑到后者对于不同性质的纳米颗粒相对贡献可能不同且在某些情况下占主导地位，从而描述其“体内”溶解的需求相关。以氧化镍为例，还提出特别有毒的纳米颗粒对肺部生理清除机制的损害可能导致肺部毒代动力学变为非线性。
