The distribution of [125I]ricin in mice following aerosol inhalation exposure.
Studies were conducted to examine the uptake and redistribution of [125I]ricin from the lungs of mice following nose-only aerosol inhalation exposure. Radiolabelled contents were measured in lung and various extra-pulmonary tissues 15 min through 30 h following 10 min aerosol exposures. Pharmacokinetic analyses were performed on whole-organ data obtained for lungs, stomach, liver and spleen. Radioactivity within the lungs, maximal at 15 min post-exposure, was eliminated in a biexponential fashion with a long beta half-life (approximately 40 h). Large amounts of radiolabel were also found within the gastrointestinal tract. Radiolabel within the stomach exhibited an absorption phase and two-compartment elimination. Radiolabel content of many other tissues, including known accumulation sites for intravenously administered toxin, was significantly (p < 0.05) increased (relative to 15 min post-exposure) in association with the early elimination of radiolabel from the lungs, but levels in these tissues were very low and did not increase after 4 h post-exposure. The only exception was our sample of trachea, which showed delayed elevations in radiolabel (peak at 24 h); this pattern was attributable to the contained thyroid (not removed at necropsy) and its trapping of free [125I] released upon tissue [125I]ricin degradation. The overall data indicate that ricin administered by aerosol inhalation is delivered to both respiratory and gastrointestinal tracts; however, it is not extensively transported from either tract to other potential target sites. Ricin delivered to the lungs is primarily sequestered within the lungs until degradation. Only small amounts of ricin delivered to the gastrointestinal tract are absorbed into the circulation.
Doebler
J A
JA
Pathophysiology Division, US Army Medical Research Institute of Chemical Defense, APG-EA, MD 21010, USA.
Wiltshire
N D
ND
Mayer
T W
TW
Estep
J E
JE
Moeller
R B
RB
Traub
R K
RK
Broomfield
C A
CA
Calamaio
C A
CA
Thompson
W L
WL
Pitt
M L
ML
D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D005753:Gastric Mucosa / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D008297:Male; D051379:Mice; D012276:Ricin / Q000493:pharmacokinetics*; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution
D000336:Aerosols; D012276:Ricin