RESUMO
Toxic industrial chemicals and chemical warfare agents present an acute inhalation hazard to exposed populations. The hazardous materials consequence assessment modeling community requires toxicity models to estimate these hazards. One popular phenomenological toxicity model is the toxic load model. Although this model is only well-defined for constant-concentration exposures, several generalizations have been proposed for the case of time-varying exposures. None of them, however, were validated by experimental evidence at the time they were proposed. Accordingly, the Defense Threat Reduction Agency (DTRA) sponsored experiments to explore the effects of time-varying inhalation exposures of hydrogen cyanide (HCN) and carbon monoxide (CO) gas on rats. The experiments were designed and executed by the U.S. Army's Edgewood Chemical and Biological Center (ECBC) and the Naval Medical Research Unit Dayton (NAMRU-D) between 2012 and 2015. We conducted an independent analysis of the toxic load model's ability to predict the ECBC/NAMRU-D experimental data using an analytical methodology oriented toward hazard prediction model users. We found that although some of the proposed extensions of the toxic load model perform better than others, all of them have difficulty reproducing the experimental data. The toxic load model also has difficulty reproducing even the constant-concentration data for HCN exposures under 10â¯min.