Studies on Poly I:C toxicity in experimental animals*1, *2

Polyinosinic:polycytidylic acid copolymer (Poly I:C), a synthetic double stranded RNA, has been proposed as a candidate for clinical introduction as an antitumor agent. In preclinical toxicologic evaluation, acute lethality studies were undertaken in 3 mouse strains, anaphylaxis studies in guinea pigs, and acute and subchronic toxicities were evaluated in rhesus monkeys and beagle dogs following daily parenteral dosing for up to 28 days. Poly I:C is more lethal to mice following iv administration than ip, and there appear to be differences in mouse strain susceptibility. No evidence of anaphylaxis was seen in guinea pigs. Signs of toxicity in dogs and monkeys were dose related, were qualitatively similar in the 2 species, and included hypoactivity, anorexia, emesis, diarrhea, ataxia and weight loss. Clinical changes included anemia, elevations of transaminases, lactic dehydrogenase, and alkaline phosphatase, decreased clotting rate and increased prothrombin time. Pathologic changes consisted of focal hemorrhages, infarction or congestion of a variety of organs, vasculitis and decreased erythroid hematopoiesis. The effects were more severe in dogs than in monkeys for equivalent mg/kg doses. In the monkey iv administration produced greater toxicity than im or ip administration. Signs of toxicity and pathologic changes appeared to be reversible in both dogs and monkeys after cessation of dosing.