INFLUENCE OF AERODYNAMIC PARTICLE SIZE ON BOTULINUM NEUROTOXIN POTENCY IN MICE

For many agents the aerodynamic particle size can affect both the virulence and disease course in animal models. Botulinum neurotoxins (BoNTs), which are widely known as potential bioterrorism agents, are toxic via multiple routes of exposure, including small particle inhalation (1-3 μm MMAD). However, the impact of larger particle sizes on the potency of BoNT has not been previously reported. Outbred mice were exposed to BoNT-containing aerosols with differing mass median aerodynamic diameters (MMADs) of 1.1, 4.9, and 7.6 microns. Collecting aerosolized BoNT onto gelatin filters or into liquid impingers resulted in equivalent estimates of aerosol concentration. Nose-only and whole-body inhalation exposure resulted in nearly identical estimates of the median lethal dose (LD50). The LD50 for inhaled BoNT increased approximately 50-fold when the median aerodynamic particle size was increased from 1.1 to 4.9 μm, from 139 (95% CI: 111-185) to 7,324 (95% CI: 4,287-10,891) mouse intraperitoneal median lethal doses (MIPLD50).