title: Benchmark dose analysis for Bacillus anthracis inhalation exposures in the nonhuman primate.
abstract: There is considerable variability in the published lethality values for inhalation exposures of Bacillus anthracis. The lack of consensus on an acceptable dose-response relationship poses a significant challenge in the development of risk-based management approaches for use following a terrorist release of B. anthracis spores. This article reviewed available B. anthracis dose-response modeling and literature for the nonhuman primate, evaluated the use of the U.S. Environmental Protection Agency's Benchmark Dose Software (BMDS) to fit mathematical dose-response models to these data, and reported results of the benchmark dose analysis of suitable data sets. The BMDS was found to be a useful tool to evaluate dose-response relationships in microbial data, including that from B. anthracis exposure. An evaluation of the sources of variability identified in the published lethality data and the corresponding BMDS-derived lethality values found that varying levels of physical characterization of the spore product, differing receptor-specific exposure assumptions, choice of dose metrics, and the selected statistical methods all contributed to differences in lethality estimates. Recognition of these contributors to variability could ultimately facilitate agreement on a B. anthracis dose-response relationship through provision of a common description of necessary study considerations for acceptable dose-response data sets.
authors.affiliation: U.S. Environmental Protection Agency, National Homeland Security Research Center, Cincinnati, OH, USA. taft.sarah@epa.gov
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Taft
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Hines
mesh_terms: D000818:Animals; D000881:Anthrax / Q000209:etiology*; D001408:Bacillus anthracis / Q000472:pathogenicity*; D058491:Bacterial Load; D023482:Bioterrorism; D016208:Databases, Factual; D004195:Disease Models, Animal; D006801:Humans; D019570:Inhalation Exposure; D008954:Models, Biological; D011323:Primates; D018570:Risk Assessment; D012308:Risk Management; D012984:Software; D014481:United States; D014484:United States Environmental Protection Agency