Pulmonary changes in rats following administration of 3-methylindole in cremophore EL.

Kiorpes, A L; Keith, I M; Dubielzig, R R

3-methylindole (3-MI) dissolved in the lipophilic carrier Cremophore EL was administered intraperitoneally to male, twelve-week-old Sprague-Dawley rats. Gross and histopathologic changes in the lungs were studied using light microscopy at three time-periods following administration: 16, 24, and 46 hours. Both 3-MI and Cremophore caused changes in bronchiolar epithelium at 16 hours. By 46 hours, Cremophore-injected rats showed no effects of the carrier; whereas, 3-MI rats showed severe lung changes characterized by airway epithelial and pulmonary vascular endothelial necrosis and sloughing, cellular infiltration by lymphocytes and macrophages, perivascular edema, alveolar edema, and lymph stasis. Grossly, the controls showed no effect of the carrier and none died during the studies. In contrast, 3-MI injected rats quickly became lethargic and displayed tachypnea, anorexia, and progressive respiratory distress. Two of five 3-MI rats in the final group died just prior to 46 hours. All of this group had grossly congested lungs and marked pleural effusion. The lesions and time course showed similarities to those observed in ruminants and mice. We conclude that 3-MI in Cremophore causes an acute progressive pneumonitis in rats and suggest that the rats may be a suitable model for 3-MI-induced and similar toxic lung diseases in domestic animals and people.