Evaluation of antiseptic drug candidate pyridosept in preclinical in vivo toxicity studies.

The purpose of this study is to assess the safety profile of the antiseptic drug candidate pyridosept in preclinical in vivo toxicity tests. The safety of pyridosept was assessed in acute toxicity tests in rats, mice and rabbits via dermal, intragastric, intraperitoneal, and inhalation routes of administration. Subchronic dermal toxicity of pyridosept was evaluated following cutaneous application for 90 days in rats and rabbits. Pyridosept was also examined in the accumulation test in rats and in micronucleus assay in the skin and bone marrow of mice after single and repeated administration. Acute oral toxicity study of pyridosept revealed an LD50 of 1208 mg/kg in mice and 1242 mg/kg in rats, a dermal LD50 > 2000 mg/kg in both species, and an LD50 of 23-32 mg/kg upon intraperitoneal administration. In the 90-day dermal toxicity study in rats, no systemic toxicity was found; the only treatment-related effects were reversible local skin reactions at intermediate and high doses. In the 90-day rabbit study, dermatitis, granulomatous hepatitis, and mild interstitial nephritis occurred; however, the incidence of hepatitis did not differ significantly from the control and showed no dose dependence. In the skin accumulation study, the cumulation coefficient (Kk = 12.8) indicated no cumulative properties, and the micronucleus assay demonstrated no mutagenic activity in mouse skin or bone marrow. Pyridosept's acute toxicity upon oral administration is more favorable than that of benzalkonium chloride, comparable to miramistin, and slightly less favorable than chlorhexidine. The results of in vivo pharmacokinetic, allergenic, and immunotoxicity studies of pyridosept will be presented in forthcoming publications.