The toxicity studies conducted with the Metronidazole 0.75% Topical Gel formulation demonstrate that the product is non-toxic in rats after acute oral administration 5g/kg and produced no ocular irritation in rabbit eyes. The formulation produced no observable effects in rabbits after dermal application of 13 mg /kg for 90 days.
No compound-related dermal or systemic effects were observed in a 13-week cutaneous route toxicity study, in which Rozex gel containing Metronidazole 0.75% w/w was applied daily to rabbits at doses ranging between 0.13 and 13 mg/kg.
Metronidazole has shown evidence of carcinogenic activity in a number of studies involving chronic, oral administration in mice and rats but not in studies involving hamsters.
One study showed a significant enhancement of UV induced skin tumours in hairless mice treated with Metronidazole intraperitoneally (15μ g per g body weight and per day for 28 weeks). Although the significance of these studies to man is not clear, patients should be advised to avoid or minimise exposure of metronidazole treated sites to sun.
Metronidazole has shown mutagenic activity in several in vitro bacterial assay systems. In addition, a dose-response increase in the frequency of micronuclei was observed in mice after intraperitoneal injection and an increase in chromosome aberrations have been reported in patients with Crohn's disease who were treated with 200 to 1200mg/day of metronidazole for 1 to 24 months. However, no excess chromosomal aberrations in circulating human lymphocytes have been observed in patients treated for 8 months.