Benchmark dose analysis for Bacillus anthracis inhalation exposures in the nonhuman primate

Area of Science:

• Environmental science and toxicology
• Microbiology and infectious disease

Background:

• Published lethality values for Bacillus anthracis (B. anthracis) inhalation exposures show significant variability.
• Lack of consensus on B. anthracis dose-response relationships impedes risk-based management strategies for spore releases.

Purpose of the Study:

• To review B. anthracis dose-response modeling and nonhuman primate literature.
• To evaluate the U.S. Environmental Protection Agency's Benchmark Dose Software (BMDS) for microbial dose-response analysis.
• To identify sources of variability in B. anthracis lethality estimates.

Main Methods:

• Literature review of B. anthracis dose-response data in nonhuman primates.
• Application of the Benchmark Dose Software (BMDS) to fit mathematical models.
• Analysis of benchmark dose for suitable B. anthracis exposure data sets.

Main Results:

• BMDS is a valuable tool for assessing dose-response relationships in microbial data, including B. anthracis.
• Variability in lethality estimates stems from spore product characterization, exposure assumptions, dose metrics, and statistical methods.
• Identified factors explain discrepancies in B. anthracis lethality estimates.

Conclusions:

• Understanding sources of variability is crucial for establishing a consensus B. anthracis dose-response relationship.
• Standardized study considerations can improve the quality and comparability of B. anthracis dose-response data.
• This facilitates more reliable risk assessment for B. anthracis exposure events.