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Dose-Response Models Incorporating Aerosol Size Dependency for Francisella tularensis



The effect of bioaerosol size was incorporated into predictive dose-response models for the effects of inhaled aerosols of Francisella tularensis (the causative agent of tularemia) on rhesus monkeys and guinea pigs with bioaerosol diameters ranging between 1.0 and 24 μm. Aerosol-size-dependent models were formulated as modification of the exponential and β-Poisson dose-response models and model parameters were estimated using maximum likelihood methods and multiple data sets of quantal dose-response data for which aerosol sizes of inhaled doses were known. Analysis of F. tularensis dose-response data was best fit by an exponential dose-response model with a power function including the particle diameter size substituting for the rate parameter k scaling the applied dose. There were differences in the pathogen's aerosol-size-dependence equation and models that better represent the observed dose-response results than the estimate derived from applying the model developed by the International Commission on Radiological Protection (ICRP, 1994) that relies on differential regional lung deposition for human particle exposure.