Impact of inhalation exposure modality and particle size on the respiratory deposition of ricin in BALB/c mice.
Ricin is a toxic lectin derived from the seed of Ricinus communis (castor plant). It is lethal in small quantities when disseminated as an aerosol. We determined the impact of using two types of exposure chambers and different particle sizes on the deposition of ricin aerosols in mice. Initially, two types of inhalation exposure chambers (whole-body [WB] or nose-only [NO]) were compared using the same size aerosol (1 micro m) to determine the potential impact upon respiratory deposition and presented dose. We then assessed the role of particle size on deposition by using aerosols with two distinctly sized particle distributions. Selected organs were collected at four time points after exposure and were analyzed by quantitative enyzme-linked immunosorbent assay (ELISA) and epifluorescence microscopy. Results of the exposure chamber comparison, using 1- micro m particles only, indicated approximately 50% of the total ricin in the 4 organs was detected in the lung tissue 1 h after exposure. The trachea and nasopharyngeal region of the animals exposed using the WB chamber contained significantly more ricin than those of animals exposed in the NO chamber. Histopathology indicated an accumulation of ricin in both the tracheobronchial and pulmonary regions with pronounced bronchiolar degradation 48 h postexposure. When particles larger than 3 micro m were used, results indicated a considerable amount of ricin initially detected in the trachea, although this finding was discounted due to the heterodispersity of the particles generated. Interestingly, no animals died as a result of exposure to the equivalent of 4 LD50s (as determined using a 1- micro m particle) when exposed to the larger size distribution of particles. This result indicates a differential lethality that is contingent upon aerosol size.
Roy
Chad J
CJ
Division of Toxinology and Aerobiology, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland 21702, USA. chad.roy@amedd.army.mi
Hale
Martha
M
Hartings
Justin M
JM
Pitt
Louise
L
Duniho
Steven
S
D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D005753:Gastric Mucosa / Q000378:metabolism; D007928:Lethal Dose 50; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000378:metabolism; D009666:Nose / Q000473:pathology; D010316:Particle Size; D012137:Respiratory System / Q000378:metabolism* / Q000473:pathology; D012276:Ricin / Q000493:pharmacokinetics* / Q000633:toxicity; D013270:Stomach / Q000473:pathology; D014132:Trachea / Q000378:metabolism / Q000473:pathology
D000336:Aerosols; D012276:Ricin