Climbazole is an imidazole antifungal agent that can provide anti-dandruff benefits when incorporated into a shampoo matrix. A series of genotoxicity studies were performed to support the human safety of this azole antifungal drug. Climbazole was not mutagenic in the Salmonella typhimurium or Escherichia coli Ames assay and did not induce micronuclei in human lymphocytes. In the mouse lymphoma assay (MLA), climbazole was negative (non-mutagenic) with and without metabolic (S9) activation after a 4h exposure; an increase in small colony mutants was observed without metabolic activation after a 24h exposure at concentrations of 15 and 17.5μg/mL. An in vivo mouse micronucleus test was negative up to a maximum tolerated dose (MTD) of 150mg/kg climbazole administered orally. In the in vivo/in vitro unscheduled DNA synthesis assay, climbazole showed no evidence of DNA damage in the livers of rats at doses up to the MTD of 200mg/kg orally. A toxicokinetic study was performed in mice with oral administration of [14C]-climbazole (150mg/kg). Radioactivity (20.42μg-equiv./g plasma) was detected 15min after oral administration of [14C]-climbazole, and the peak concentration was 62.96μg-equiv./g plasma at 8h after dosing. The measured amounts of radioactivity in plasma, at all sample times from 15min up to 24h, exceeded the concentrations that induced increases in mutation frequency after 24h exposure of mouse lymphoma cells in vitro (15 and 17.5μg/mL). These observations lend support to the conclusion that climbazole does not present a genotoxic risk in vivo. Furthermore, these data are consistent with the published data for other azole antifungals that work by preventing the synthesis of ergosterol and, as a class, are generally non-genotoxic, except some isolated positive results of questionable significance. Collectively, these data are supportive of the view that climbazole does not present a genotoxic or carcinogenic risk to humans.