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Benchmark Dose Analysis for Bacillus anthracis Inhalation Exposures in the Nonhuman Primate

Authors

  • Sarah C. Taft,

    Corresponding author
      Sarah C. Taft, U.S. Environmental Protection Agency, National Homeland Security Research Center, 26 West Martin Luther King Drive, MS-NG-16, Cincinnati, OH 45268, USA; tel: 513-569-7037; fax: 513-487-2555; taft.sarah@epa.gov.
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    • U.S. Environmental Protection Agency, National Homeland Security Research Center, Cincinnati, OH, USA.

  • Stephanie A. Hines

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    • Battelle Memorial Institute, Columbus, OH, USA.


Sarah C. Taft, U.S. Environmental Protection Agency, National Homeland Security Research Center, 26 West Martin Luther King Drive, MS-NG-16, Cincinnati, OH 45268, USA; tel: 513-569-7037; fax: 513-487-2555; taft.sarah@epa.gov.

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.

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