Toxicology Excellence for Risk Assessment (TERA), 2300 Montana Avenue, Suite 409, Cincinnati, OH 45211, USA.
Regul Toxicol Pharmacol. 2013 Jun;66(1):47-58. doi: 10.1016/j.yrtph.2013.02.003. Epub 2013 Feb 27.
A biomathematical model was previously developed to describe the long-term clearance and retention of particles in the lungs of coal miners. The model structure was evaluated and parameters were estimated in two data sets, one from the United States and one from the United Kingdom. The three-compartment model structure consists of deposition of inhaled particles in the alveolar region, competing processes of either clearance from the alveolar region or translocation to the lung interstitial region, and very slow, irreversible sequestration of interstitialized material in the lung-associated lymph nodes. Point estimates of model parameter values were estimated separately for the two data sets. In the current effort, Bayesian population analysis using Markov chain Monte Carlo simulation was used to recalibrate the model while improving assessments of parameter variability and uncertainty. When model parameters were calibrated simultaneously to the two data sets, agreement between the derived parameters for the two groups was very good, and the central tendency values were similar to those derived from the deterministic approach. These findings are relevant to the proposed update of the ICRP human respiratory tract model with revisions to the alveolar-interstitial region based on this long-term particle clearance and retention model.
先前开发了一种生物数学模型来描述煤矿工人肺部中颗粒的长期清除和保留情况。该模型结构在两个数据集(一个来自美国,一个来自英国)中进行了评估,并对参数进行了估计。三腔室模型结构包括吸入颗粒在肺泡区域的沉积、从肺泡区域清除或转移到肺间质区域的竞争过程,以及间质化物质在肺相关淋巴结中非常缓慢、不可逆的隔离。分别为两个数据集估计了模型参数值的点估计值。在当前的研究中,使用马尔可夫链蒙特卡罗模拟的贝叶斯群体分析被用来重新校准模型,同时改善了对参数可变性和不确定性的评估。当模型参数同时对两个数据集进行校准时,两个组的导出参数之间的一致性非常好,中心趋势值与从确定性方法中得出的值相似。这些发现与 ICRP 人类呼吸道模型的更新有关,该模型基于该长期颗粒清除和保留模型对肺泡-间质区域进行了修订。