Comparison of Deposition Patterns for Small and Large Particle Aerosolized Toxins and Resulting Disease in Guinea Pigs and African Green Monkeys

The battlefield risk from toxic industrial chemicals, materials, or threat agents is aerosol exposure. In most cases, this is not the natural route of exposure, so we must rely on animal models to predict disease course in humans. Deposition patterns for small (1μm) and large (8μm) particles were easily predicted, but effect on disease course for Ricinus communis (ricin) was unknown. Ricin small particle: Guinea Pig (GP) – histopathologic findings (lung) were absent at 1-hr timepoint, but present by 6-hr. Ricin deposition at 6-hr was less than that at the 1-hr timepoint. After 24 hr, pulmonary changes represented significant progression of disease and amount of ricin in lungs was significantly decreased. After 48 hr, there was advanced progression of disease and amount of ricin in the lungs was comparable to 24-hr timepoint. Ricin large particle: GP – minor changes in large airways represented early pathological effects of aerosol ricin exposure at all timepoints; significantly diminished compared to pathology of small particles. Compared to small particle, abundant ricin antigen was detected in nasal cavity at these timpoints. The cohort of GP exposed to large particle ricin euthanized at 1-hr and 6-hr postchallenge contained abundant ricin antigen in large pulmonary airways and nasal passages. In contrast, only small amounts of ricin antigen were detected in lungs of GP exposed to large particle ricin euthanized at 48-hr; furthermore, immunopositive staining was absent in the nasal cavity and contiguous airway passages. Ricin small particle: African green monkey (AGM) – Lung pathology at 4 or 8-hr post-exposure was normal, but at 16, 24, and 36-hr, progression of changes due to acute ricin intoxication was present. Deposition patterns were similar to small particle in GP. Ricin large particle: three AGM survived without developing clinical signs of illness. Both the GP and AGM were most susceptible and disease progression most severe after inhalational exposure to a 1μm aerosol. Although some GP were susceptible to large particles, there was a delayed time to death, compared to death due to a small particle aerosol. AGM were not affected by an 8μm aerosol. These different outcomes are important for risk assessment of human health factors on the battlefield. Leffel, E.K.; Hartings, J.M.; Pitt, M.L.M.; Stevens, E. (2007) Comparison of Deposition Patterns for Small and Large Particle Aerosolized Toxins and Resulting Disease in Guinea Pigs and African Green Monkeys. In Defence against the Effects of Chemical Hazards: Toxicology, Diagnosis and Medical Countermeasures (pp. 11-1 – 11-12). Meeting Proceedings RTO-MP-HFM-149, Paper 11. Neuilly-sur-Seine, France: RTO. Available from: http://www.rto.nato.int. Comparison of Deposition Patterns for Small and Large Particle Aerosolized Toxins and Resulting Disease in Guinea Pigs and African Green Monkeys 11 2 RTO-MP-HFM-149 "Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the U.S. Army."