Mutagenicity of oxytetracycline

Oxytetracycline hydrochloride, potassium nitrite and a combination of this antibiotic with the nitrite were tested for their mutagenicity in the host-mediated assay with mice as the host animals. The Salmonella typhimurium strain used was his G46. The bacteria were injected intraperitoneally, and the test compounds were administered by a stomach tube. Neither oxytetracycline nor potassium nitrite were mutagenic for strain G46, but the combination of the compounds administered in the highest tolerated doses proved to be mutagenic for this Salmonella strain. The mutagenicity of the compounds was further evaluated by the micronucleus test in the bone marrow of Swiss mice. The test compounds were administered p.o., half the dose 30 h and the rest 6 h before the animals were killed. Oxytetracycline and the combination of oxytetracycline with potassium nitrite induced a significant increase in the frequency of micronuclei in polychromatic erythrocytes. Dose-response experiments with oxytetracycline and with the combination of the antibiotic with nitrite revealed an apparent no-effect level at 2 X 50 to 2 X 500 mg/kg. At higher doses both oxytetracycline and oxytetracycline with nitrite significantly influenced the ratio of erythrocytes to nucleated cells. The findings were compared with data obtained with dimethylnitrosamine included in both kinds of experiment.