THE COMPARATIVE TOXICOLOGY OF NARASIN IN LABORATORY-ANIMALS

The toxicology of narasin has been extensively investigated in several species of laboratory animals. Acute median lethal po doses varied co nsiderably between species (>10 to 40.8 mg/kg). Animals of various spe cies given acutely toxic doses of narasin manifested similar clinical signs of toxicity, including anorexia, hypoactivity, leg weakness, ata xia, depression and diarrhea. Clinical effects were usually delayed 1 to several days, depending on the dose, and some were reversible even with continued narasin administration. In repeated dose toxicity studi es, narasin dosages have been demonstrated at which animals could be e xposed daily for long periods of time without producing harmful effect s. The no-observed effect levels (NOELs) by the dietary route were 60 ppm in mice and 15 ppm in rats after 3 mo of dosing and 15 ppm in rats after 1 y. In dogs, NOELs were 1 mg/kg body weight after 3 mo and 0.5 mg/kg body weight after 1 y of dosing. In breeding animals, narasin d id not affect reproductive performance through 4 generations and was n ot teratogenic. Two-y chronic bioassays in 2 rodent species showed tha t narasin did not produce cumulative toxicity or carcinogenicity. In g enetic toxicity tests narasin was not mutagenic to bacterial or mammal ian cells and did not induce DNA repair or sister chromatid exchange. Narasin neither caused dermal toxicity nor skin sensitization, but was a severe eye irritant in rabbits. In dogs, local irritation and syste mic toxicity occurred following repeated inhalation exposure to narasi n aerosol concentrations greater than 0.114 mg/m3 of air. Cardiovascul ar effects were observed in anesthetized and conscious dogs given dose s of 0.0076 to 0.153 mg/kg iv, but not in dogs dosed po with 1.53 mg n arasin/kg body weight. The primary target organs of narasin toxicity w ere skeletal and cardiac muscles; peripheral nerves were also affected in dogs.