Assessment of chronic toxicity and carcinogenicity in an accelerated cancer bioassay in rats of moxifloxacin, a quinolone antibiotic

The chronic toxicity and carcinogenicity of Moxifloxacin (MOX), a bacterial gyrase-inhibiting fluoroquinolone antibiotic, were studied in male and fem ale Wistar rats in an accelerated cancer bioassay (ACB). The ACB is a mecha nistic initiation/promotion chronic toxicity and carcinogenicity study desi gned to assess potential carcinogenic activity of a test substance in criti cal organs in which human carcinogens are active. The organs studied were l iver, lungs, urinary bladder, mammary gland, bone marrow, thymus, spleen an d stomach. MOX was given daily by intragastric instillation at 500 mg/kg bw /day for the first 13 weeks to produce potential initiation, followed by pr omoters (PROs) for 24 weeks, or for the last 24 weeks after 13 weeks of exp osure to initiators (INs). The INs, administered during the first 13 weeks, were diethylnitrosamine for the liver, N-n-butyl-N-(4-hydroxybutyl)nitrosa mine for the urinary bladder, ethylnitrosourea for the hematolymphoreticula r system, N-nitrosodimethylamine for lungs, methylnitrosourea for the stoma ch and 7,12-dimethylbenz(a)-anthracene for the mammary gland. The PROs, adm inistered during the last 24 weeks after MOX, were phenobarbital for the li ver, nitrilotriacetic acid for the urinary bladder, azathioprine for the bo ne marrow, butylated hydroxytoluene for the lung, butylated hydroxyanisole for the forestomach, and diethylstilbestrol for the mammary gland. The INs produced preneoplastic and neoplastic lesions which were not enhanced by MO X, and MOX plus PROs elicited no neoplastic effects, documenting that MOX d id not produce either initiation or promotion of neoplasia in any of the ta rget sites, or in any of the other twenty tissues examined.