Studies on the toxicological profile of the local anaesthetic articaine.

The toxicity of articaine (CAS 23964-58-1) and of a respective preparation (Septanest SP; 4% articaine HCl and epinephrine 1: 100,000) was examined in in vitro and in vivo experiments. The following endpoints were examined: repeated dose toxicity, reproduction toxicity, mutagenic potential and local tolerance. Repeated s.c. administration of articaine HCl in rats and dogs demonstrated no pathomorphological systemic changes even at systemically toxic doses. The no-effect level (NOEL) was 25 mg articaine HCl/kg b.w./day s.c. for the rat and 40 mg articaine HCl/kg b.w./day s.c. for the dog. Reproduction studies were performed in rats and rabbits at doses up to more than 10 times the maximum recommended human dose of 7 mg articaine HCl/kg b.w. and revealed no evidence of harm to the foetus or to other aspects of reproduction, even at doses toxic to the parental animals. Four standard in vitro and in vivo mutagenicity studies have shown no mutagenic potential up to cytotoxic concentrations or up to the maximum tolerated dose level. The local tolerance of articaine HCl was good to very good. The preclinical data indicate that articaine HCl does not possess any relevant side-effects or gross toxicity and can be considered a safe local anaesthetic.