Lack of mutagenicity of levofloxacin in lacZ transgenic mice

The mutagenic effects of levofloxacin in lacZ transgenic mice (Muta Mouse) have been investigated. Male Muta-Mouse mice were administered levofloxacin i.p. at a dose of 300 or 600 mg/kg. The higher dose corresponded to half the LD50 of the compound in ddY strain mice. The mutant frequencies in the bone marrow, liver (day 10 only), testis and sperm were examined by the positive selection method for lacZ mutations on days 1 and 10 after treatment. Levofloxacin did not induce any statistically significant increase in mutant frequency in any of the examined tissues at either dose level or at either sampling time. The mutant frequency increases over the spontaneous values in the bone marrow, liver, testis and sperm were 1.0- to 1.2-fold, 0.9-fold, 0.5- to 1.0-fold and 0.9- to 1.3-fold respectively. N-Ethyl-N-nitrosourea (100 mg/kg as a positive control), on the other hand, induced significant increases in mutant frequencies in both somatic cells (bone marrow and liver) and germ cells (testis and sperm) on day 10 after treatment. The mutagenic potency for ENU was bone marrow >> liver approximately testis approximately sperm (50.1-fold, 3.4-fold, 2.9-fold and 2.3-fold respectively over the spontaneous values). Levofloxacin was not mutagenic in the lacZ transgenic mice under the present experimental conditions.