SOME TOXICOLOGICAL AND PHARMACOLOGICAL PROPERTIES OF THE PROTEOLYTIC ENZYME, FICIN

¹ From the Merck Institute for Therapeutic Research, Rahway, New Jersey

(1) The peroral and intravenous toxicity of ficin was determined in mice, rats, guinea pigs, rabbits, cats, and dogs. A considerable variation in sensitivity among different species was observed. The L.D. 50 for rats and mice following oral administration is about 10 grams per kilogram and in rabbits and guinea pigs about 5 grams per kilogram. The toxicity following intravenous administration (50 to 100 mgm. per kilogram) is in contrast to the low toxicity by the oral route.

(2) The toxicity of ficin depends primarily upon the total amount of drug administered and is practically independent of the concentration.

(3) The toxicity of a given dose of ficin can be reduced by subdivision into smaller doses and repeated administration.

(4) The signs following sublethal doses consist of vomiting, bloody diarrhea, and general prostration. Upon autopsy there is severe irritation of the gastrointestinal tract ranging from inflammatory reactions to erosions.

(5) Parenteral injection of ficin causes severe tissue damage. This is also observed on topical application of ficin to wounds or denuded skin and particularly to the conjunctival surfaces.

(6) Repeated daily peroral administration of ficin does not alter the outcome of liver and kidney function tests.

(7) Intravenous injection of small doses of ficin reduces the erythrocyte count and prolongs markedly the blood clotting time.

(8) On the basis of sensitization to anaphylactic shock there is no evidence of absorption of ficin from the intact gastrointestinal tract.