Gadobutrol

Lethality was observed in rodents after a single intravenous administration of 20 mmol/kg. This represents a dose of at least 2 orders of magnitude higher than the standard single diagnostic dose in humans (0.1 mmol/kg). No carcinogenicity studies have been conducted. No mutagenesis was observed in vitro in reverse mutation tests in bacteria, or in the HGPRT (hypoxanthine-guanine phosphoribosyl transferase) test using Chinese hamster V79 cells. Similarly, no mutagenesis was seen in chromosome abberation tests of human peripheral blood lymphocytes. It was also negative in in-vivo micronucleus tests in mice following a 0.5mmol/kg intravenous injection. No fertility or reproductive impairment was observed in male and female rates given doses 12.2 times human equivalent doses, based on body surface area. Intolerance reactions local to the injection site have been observed in rabbits after paravenous administration, and are associated with the infiltration of inflammatory cells, suggesting the possibility of local irritation if the contrast medium leaks around veins in a clinical setting.