THE DISTRIBUTION OF [I-125] RICIN IN MICE FOLLOWING AEROSOL INHALATION EXPOSURE

Studies were conducted to examine the uptake and redistribution of [I- 125]ricin from the lungs of mice following nose-only aerosol inhalatio n exposure. Radiolabelled contents were measured in lung and various e xtra-pulmonary tissues 15 min through 30 h following 10 min aerosol ex posures, Pharmacokinetic analyses were performed on whole-organ data o btained for lungs, stomach, liver and spleen. Radioactivity within the lungs, maximal at 15 min post-exposure, was eliminated in a biexponen tial fashion with a long beta half-life (similar to 40 h). Large amoun ts of radiolabel were also found within the gastrointestinal tract. Ra diolabel within the stomach exhibited an absorption phase and two-comp artment elimination, Radiolabel content of many other tissues, includi ng known accumulation sites for intravenously administered toxin, was significantly (p < 0.05) increased (relative to 15 min post-exposure) in association with tile early elimination of radiolabel from the lung s, but levels in these tissues were very low and did not increase afte r 4 h post-exposure, The only exception was our sample of trachea, whi ch showed delayed elevations in radiolabel (peak at 24 h); this patter n was attributable to the contained thyroid (not removed at necropsy) and its trapping of free [I-125] released upon tissue [I-125]ricin deg radation. The overall data indicate that ricin administered by aerosol inhalation is delivered to both respiratory and gastrointestinal trac ts; however, it is not extensively transported from either tract to ot her 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 ci rculation.