Comparative mutagenicity testing of ceftiofur sodium: III. Ceftiofur sodium is not an in vivo clastogen

Abstract

Ceftiofur has been previously shown (Aaron et al., 1995a Mutation Res., this issue) to produce chromosome aberrations following extended treatment of Chinese hamster ovary cells in culture at high doses in the absence of S9 activation. The experiments described here address the relevance of this finding in vivo. Ceftiofur failed to induce aberrations in the bone marrow of CD-1 mice following intraperitoneal injection. Furthermore, ceftiofur did not induce micronucleated polychromatic erythrocytes in mouse bone marrow. In the experiments reported here no evidence of the induction of unscheduled DNA synthesis in the liver of rats treated in vivo was seen following oral exposure to high doses of the drug. However, the compound was foud to reach the bone marrow compartment in these experiments. Thus, the negative finding suggests that the in vitro finding of chromosome aberration induction by ceftiofur is not a cause of concern. This assertion is supported by mechanistic studies (Aaron et al., 1995b, Mutation Res., this issue) which show the cause of the in vitro findings to be most likely due cell cycle delay and by the observation that ceftiofur is rapidly metabolized in mammalian systems in vivo but not in the artificial conditions that occur in the in vitro experiments.