Toxicity studies with human fibroblast interferon.

Abstract

Acute toxicity studies of interferon derived from human fibroblasts (FHIF) were performed in mice and rats with doses between 6 X 10(4) and 480 X 10(4) IU/kg i.v. and an observation period of 14 days. No severe toxic effects, such as loss of weight or other pathological clinical signs were observed. In local innocuity studies (i.v., i.a., paravenous) in rabbits FHIF proved to have no adverse effects. 180,000 IU/kg were pyrogen free in rabbits, in the limulus test the content of lipopolysaccharides (LPS) was 208 pg/ml as compared to the FDA standard EC-2. Studies were performed to assess the pharmacological safety of FHIF in 10 monkeys (Macaca fascicularis). The i.v. injection of 60,000 IU/kg had no pathological effects on circulation, respiration, number of blood cells, or body temperature. In six monkeys a short decrease of arterial blood pressure was noted a few minutes after injection of 120,000 IU/kg i.v. Both doses caused an increase of thrombelastographic time (TEG). The proposed single human dose of approximately 60,000 IU/kg has been proved safe in the acute toxicity studies and the pharmacological safety assessment in mice, rats, rabbits, and monkeys. The LPS content is low.