Bartrand Timothy A, Weir Mark H, Haas Charles N
Department of Civil, Architectural and Environmental Engineering, Drexel University, Philadelphia, PA, USA.
Risk Anal. 2008 Aug;28(4):1115-24. doi: 10.1111/j.1539-6924.2008.01067.x. Epub 2008 Jun 28.
Because experiments with Bacillus anthracis are costly and dangerous, the scientific, public health, and engineering communities are served by thorough collation and analysis of experiments reported in the open literature. This study identifies available dose-response data from the open literature for inhalation exposure to B. anthracis and, via dose-response modeling, characterizes the response of nonhuman animal models to challenges. Two studies involving four data sets amenable to dose-response modeling were found in the literature: two data sets of response of guinea pigs to intranasal dosing with the Vollum and ATCC-6605 strains, one set of responses of rhesus monkeys to aerosol exposure to the Vollum strain, and one data set of guinea pig response to aerosol exposure to the Vollum strain. None of the data sets exhibited overdispersion and all but one were best fit by an exponential dose-response model. The beta-Poisson dose-response model provided the best fit to the remaining data set. As indicated in prior studies, the response to aerosol challenges is a strong function of aerosol diameter. For guinea pigs, the LD(50) increases with aerosol size for aerosols at and above 4.5 mum. For both rhesus monkeys and guinea pigs there is about a 15-fold increase in LD(50) when aerosol size is increased from 1 mum to 12 mum. Future experimental research and dose-response modeling should be performed to quantify differences in responses of subpopulations to B. anthracis and to generate data allowing development of interspecies correction factors.
由于用炭疽芽孢杆菌进行实验成本高昂且危险，因此对公开文献中报道的实验进行全面整理和分析有助于科学界、公共卫生界和工程界。本研究从公开文献中识别出吸入炭疽芽孢杆菌的剂量反应数据，并通过剂量反应建模来描述非人类动物模型对刺激的反应。在文献中发现了两项涉及四个适合剂量反应建模数据集的研究：两个豚鼠对Vollum和ATCC - 6605菌株鼻内给药反应的数据集，一个恒河猴对Vollum菌株气溶胶暴露反应的数据集，以及一个豚鼠对Vollum菌株气溶胶暴露反应的数据集。所有数据集均未表现出过度离散，除一个数据集外，其余均最适合指数剂量反应模型。β - 泊松剂量反应模型对其余数据集拟合效果最佳。如先前研究所示，对气溶胶刺激的反应是气溶胶直径的强函数。对于豚鼠，当气溶胶直径为4.5微米及以上时，半数致死剂量（LD(50)）随气溶胶大小增加。当气溶胶大小从1微米增加到12微米时，恒河猴和豚鼠的LD(50)均增加约15倍。未来应开展实验研究和剂量反应建模，以量化亚群体对炭疽芽孢杆菌反应的差异，并生成数据以制定种间校正因子。
