Microscopic Changes Produced in Tissues of Animals Injected with Thorium Dioxide for Splenc-hepatography

Abstract

Many reports have recently appeared upon the results of the intravenous injection of colloidal thorium dioxide (Thorotrast-Heyden) in the experimental animal, most of them demonstrating tolerance and lack of toxicity even in large doses. Huguenin and Nemours 1 state that 18 cc. of thorotrast were tolerated by the rabbit without any after-effects. Later, however, with Albot, 2 they described the production of hepatitis and cirrhosis in rabbits with doses of 15 to 20 cc. Bauman and Schilling 3 found that 1 cc. administered intravenously in rabbits, was necessary for contrast shadows of the spleen and liver but that 3 cc. twice daily up to 12 cc. gave more distinctive shadows, with no ill effects. Fifteen minutes after injection, glossy colorless grains could be observed in the various stellate (Kupffer) cells and also in the reticulum cells of the spleen. Twenty-four hours later, such cells were swollen and filled with fine and coarse, glossy granules. After 14 days the same approximate condition existed. Popper and Klein 4 injected rabbits and dogs up to 8 times the quantity recommended for the human subject. They state it was harmless and that the blood was not affected. Lambin, 5 however, found that 5 cc. per kilo in rabbits necessary for liver visualization caused anemia whereas 1 cc. per kilo, sufficient for spleen visualization, caused an erythroblastic reaction, without producing anemia. When a pronounced anemia was produced, the recovery was spontaneous. Kadrnka 6 reports haematuria in animals subsequent to intravenous injections of thorium dioxide. Thus conflicting observations have been recorded.

We injected 53 white rats in collaboration with radiological observations of Drs. Menville and Ané, with variable results as regards tolerance. The very moderate dosage was from 0.2 to 1 cc.