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Dose-response models for inhalation of Bacillus anthracis spores: interspecies comparisons
Journal article   Peer reviewed

Dose-response models for inhalation of Bacillus anthracis spores: interspecies comparisons

Timothy A Bartrand, Mark H Weir and Charles N Haas
Risk analysis, v 28(4), pp 1115-1124
Aug 2008
PMID: 18554269

Abstract

Dose-Response Relationship, Drug Bacillus anthracis - physiology Animals Guinea Pigs Species Specificity Humans Inhalation Exposure Poisson Distribution Spores, Bacterial Macaca mulatta Lethal Dose 50
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.

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Web of Science research areas
Mathematics, Interdisciplinary Applications
Public, Environmental & Occupational Health
Social Sciences, Mathematical Methods
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