Toxicological studies with therapeutically-applicable Vibrio cholerae neuraminidase.

Neuraminidase was submitted to a preclinical toxicological investigation in short--and long--term experiments. The acute toxicity in mice, rats, and guinea pigs is low (LD 50 i.v.: mouse 30,000 units/kg, rat 44,000 units/kg, guinea pig 7,700 units/kg; s.c.: mouse, rat, guinea pig more than 30,000 u/kg). After i.v. injection into dogs, respiration is not at all and blood pressure only slightly altered. Neuraminidase is pyrogenfree in the rabbit test. Assays of antigenicity in guinea pigs and tests on local i.v., i.m., s.c. toxicity in rabbits and guinea pigs showed only moderate toxic signs. Chronicity studies were performed in dogs and rats over 90 days with repeated administration of various amounts of Neuraminidase (dogs 50-2,000 u/kg, rats 500-2,000 u/kg i.v., 26 or 65 injections). Only in very high dose levels (more than 500 u/kg) Neuraminidase was toxic in dogs (damage of liver, kidney and erythrocytes). In lower doses in dogs and in rats the clinical, biochemical, and hematological data as well as urinalysis and anatomopathological results give no evidence of systemic or important alterations which would preclude the clinical investigation of the drug.