Inhalation Toxicology and Histopathology of Ricin and Abrin Toxins

Abstract

The inhalation toxicology of ricin (supplied by Sigma) from the seed variety “Hale Queen” and abrin was examined following head-only exposure of rats to a range of concentrations of each toxin generated as an aerosol from solution using a constant-output nebulizer. The inhalation toxicity of an in-house preparation of ricin from a different seed type, Ricinus communis var. zanzibariensis (R. zanzibariensis), was also assessed for comparison. The approximate LCt50 values determined were very similar for the Sigma ricin and abrin (4.54–5.96 and 4.54 mg min m-3, respectively). However, the LCt50 of ricin toxin prepared in-house from seeds of the R. zanzibariensis variety was assessed to be 12.7 mg min m-3. Ricin prepared from this seed variety was therefore less toxic than Sigma ricin by a factor of almost threefold. Given that both ricin preparations were pure by silver-stained, sodium dodecyl sulfate polyacrylamide electrophoresis gels, the data must reflect differences in specific toxicity between seed varieties. The histopathology was studied in a separate group of experimental animals exposed to approximate LCt30 levels of each in-house toxin preparation and was found to be entirely restricted to the lung. The overall pattern and time course of damage observed were similar for ricin and abrin and were characterized by rapidly progressive and overwhelming pulmonary edema accompanied by acute destructive alveolitis and necrosis/apoptosis of the lower respiratory tract epithelium; severe intraalveolar edema and resulting hypoxia accounted for the majority of deaths in the decedent population. The resolution phase of the pulmonary damage in those animals destined to survive was heralded by a gradual disappearance of edema fluid accompanied by generalized, focally florid, hyperplasia of type II pneumocytes and striking transitory consolidation of the lung parenchyma by chronic inflammatory cells. Despite many similarities in histopathology between abrin and ricin there were some differences. Although by systemic administration abrin is several times more toxic than ricin, when delivered by inhalation there was no significant difference in potency between abrin and the commercial preparation of ricin (Sigma).