REPRODUCTIVE TOXICITY STUDIES OF D-CAMPHOR IN RATS AND RABBITS

The embryotoxicity of D-Camphor (GAS 76-22-2), orally employed for the treatment of hypotonic circulatory dysregulations, was investigated i n rats and rabbits. D-Camphor elicited no evidence of teratogenicity w hen administered orally during the fetal period of organogenesis to pr egnant rats at doses up to 1000 mg/kg b.w./day, and to pregnant rabbit s 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, pile-erection, reduced m otility and reduced body weight gain. In rabbit dams the high dose lev el of 681 mg/kg b.w./d p.o. resulted in reduced body weight gain and f ood consumption. No increased incidence in variations, retardations or malformations were observed at any of the treated dose levels not eve n at the highest tested dose level (rat: 1000 mg/kg b.w./d p.o.; rabbi t: 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 c onditions the therapeutic ratio is above 450 for the endpoint embryoto xicity reflecting a wide margin of safety.