STUDIES ON THE TOXICITY OF ACTINOMYCIN

¹ From the Merck Institute for Therapeutic Research, Rahway, N. J. and the New Jersey Agricultural Experiment Station, Rutgers University, Department of Soil Chemistry and Microbiology, New Brunswick

1. Doses of 1.0 mgm. or more of actinomycin per kilogram are lethal for mice, rats and rabbits when administered intravenously, intraperitoneally, subcutaneously or orally. The toxicity is more evident when observations are extended over a seven day period.

2. Doses as small as 50 micrograms per kilogram intraperitoneally produce death in mice or rats when administered daily over a six-day period. Death is accompanied by severe gross pathological changes, notably a marked shrinkage of the spleen.

3. Liver and kidney function appear to be impaired following daily administration of actinomycin.

4. Intravenous injection of actinomycin produces no significant changes in blood pressure or respiration.

5. Actinomycin is markedly bacteriostatic in vitro for both aerobic and anaerobic pathogenic bacteria.

6. In vivo, actinomycin affords almost no protection to mice inoculated with Streptococcus hemolyticus or pneumococcus type I. Some effect is found in Trypanosoma equiperdum infections.

7. Analysis of the fate of actinomycin upon intravenous injection indicates that it is rapidly removed from the blood and is found in various quantities in all organs of the body. Rabbits excrete 10 to 20 per cent of the actinomycin 5 to 6 hours after injection.