Gutting Bradford W, Rukhin Andrey, Mackie Ryan S, Marchette David, Thran Brandolyn
CBR Concepts and Experimentation Branch (Z21), Naval Surface Warfare Center, Dahlgren Division, Dahlgren, VA, USA.
Sensor Fusion Branch (Q33), Naval Surface Warfare Center, Dahlgren Division, Dahlgren, VA, USA.
Risk Anal. 2015 May;35(5):811-27. doi: 10.1111/risa.12326. Epub 2014 Dec 24.
The application of the exponential model is extended by the inclusion of new nonhuman primate (NHP), rabbit, and guinea pig dose-lethality data for inhalation anthrax. Because deposition is a critical step in the initiation of inhalation anthrax, inhaled doses may not provide the most accurate cross-species comparison. For this reason, species-specific deposition factors were derived to translate inhaled dose to deposited dose. Four NHP, three rabbit, and two guinea pig data sets were utilized. Results from species-specific pooling analysis suggested all four NHP data sets could be pooled into a single NHP data set, which was also true for the rabbit and guinea pig data sets. The three species-specific pooled data sets could not be combined into a single generic mammalian data set. For inhaled dose, NHPs were the most sensitive (relative lowest LD50) species and rabbits the least. Improved inhaled LD50 s proposed for use in risk assessment are 50,600, 102,600, and 70,800 inhaled spores for NHP, rabbit, and guinea pig, respectively. Lung deposition factors were estimated for each species using published deposition data from Bacillus spore exposures, particle deposition studies, and computer modeling. Deposition was estimated at 22%, 9%, and 30% of the inhaled dose for NHP, rabbit, and guinea pig, respectively. When the inhaled dose was adjusted to reflect deposited dose, the rabbit animal model appears the most sensitive with the guinea pig the least sensitive species.
通过纳入吸入性炭疽的新的非人灵长类动物（NHP）、兔子和豚鼠的剂量-致死率数据，扩展了指数模型的应用。由于沉积是吸入性炭疽发病的关键步骤，吸入剂量可能无法提供最准确的跨物种比较。因此，推导了物种特异性沉积因子，以将吸入剂量转换为沉积剂量。使用了四个NHP、三个兔子和两个豚鼠的数据集。物种特异性合并分析的结果表明，所有四个NHP数据集可以合并为一个单一的NHP数据集，兔子和豚鼠的数据集也是如此。这三个物种特异性合并数据集不能合并为一个单一的通用哺乳动物数据集。对于吸入剂量，NHP是最敏感的（相对最低的LD50）物种，兔子是最不敏感的。建议用于风险评估的改进吸入LD50分别为NHP、兔子和豚鼠的50,600、102,600和70,800个吸入孢子。利用已发表的芽孢杆菌孢子暴露沉积数据、颗粒沉积研究和计算机建模，估算了每个物种的肺沉积因子。NHP、兔子和豚鼠的沉积量分别估计为吸入剂量的22%、9%和30%。当调整吸入剂量以反映沉积剂量时，兔子动物模型似乎最敏感，豚鼠是最不敏感的物种。
