Reproductive toxicity studies of D-camphor in rats and rabbits

The embryotoxicity of D-Camphor (CAS 76-22-2), orally employed for the treatment of hypotonic circulatory dysregulations, was investigated in rats and rabbits. D-Camphor elicited no evidence of teratogenicity when administered orally during the fetal period of organogenesis to pregnant rats at doses up to 1000 mg/kg b.w./day, and to pregnant rabbits at doses up to 681 mg/kg b.w./day. The no-observed-effect level for the fetal organism for the rat was above 1000 mg/kg b.w., and for the rabbit above 681 mg/kg b.w. In rat dams a dose-dependent reduction in food intake and salivation was noted from 464 mg/kg b.w./p.o. onwards. The high dose of 1000 mg/kg b.w./d p.o. resulted in fairly pronounced signs of toxicity such as clonic convulsion, pilo-erection, reduced motility and reduced body weight gain. In rabbit dams the high dose level of 681 mg/kg b.w./d p.o. resulted in reduced body weight gain and food consumption. No increased incidence in variations, retardations or malformations were observed at any of the treated dose levels not even at the highest tested dose level (rat: 1000 mg/kg b.w./d p.o.; rabbit: 681 mg/kg b.w./d p.o.). The daily maximum human therapeutic camphor dose is approximately 1.43 mg/kg b.w. Hence, under the present test conditions the therapeutic ratio is above 450 for the endpoint embryotoxicity reflecting a wide margin of safety.