Toxicity of Sulfanilamide. A Study of the Pathological Lesions in White Mice. ∗

Abstract

Since the introduction of sulfanilamide and related substances as chemotherapeutic agents, there have appeared in the literature several reports on their toxicity for experimental animals. Domagk 1 observed that 0.5 gm. per kilo of ‘Prontosil Insoluble’† given orally was well tolerated by mice and dogs, whereas the cat tolerated only 0.2 gm. per kilo. The urine of dogs which were exposed to varying amounts of ‘Prontosil Insoluble’ over a period of 14 days showed no red or white blood cells or casts. Similar studies were carried on by Buttle, Gray and Stephenson, 2 who found oral dosages of 0.6 gm. per kilo of ‘Prontosil Insoluble’ innocuous for mice. Larger doses, 1.25 and 5 gm. per kilo proved fatal in the majority of instances. These investigators also studied the toxicity for mice of sulfanilamide given orally and found 2.5 gm. per kilo well tolerated, whereas 5 gm. per kilo killed 2 of 6 animals and 10 gm. per kilo killed 6 out of 6. Rosenthal, 3 studying the toxicity of sulfanilamide for mice, reported 6 gm. per kilo as the fatal dose when given subcutaneously in olive oil. Two gm. per kilo produced spastic extremities, flexion of the spine, excitability and incoördination which disappeared after 12 hours. In a similar manner, Raiziss and his coworkers 4 found 1-2 gm. of sulfanilamide given subcutaneously to be well tolerated by mice, whereas 2.5 and 3 gm. proved to be a fatal dose. Maximum tolerated oral dosage for rabbits was found to be 1.5 gm. per kilo.

Up to the present time all published data relevant to toxicity of sulfanilamide for animals has presented maximum tolerated and lethal dosages. No studies of gross or microscopic pathology produced by sulfanilamide in animals have appeared in the literature.