Leuschner J
LPT Laboratory of Pharmacology and Toxicology, Hamburg, Germany.
Arzneimittelforschung. 1997 Feb;47(2):124-8.
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.
对口服用于治疗低张性循环调节障碍的 D-樟脑（化学物质登录号 76-22-2）进行了大鼠和家兔胚胎毒性研究。在器官形成期的胎儿阶段，对妊娠大鼠口服给予高达 1000 mg/kg 体重/天的剂量，对妊娠家兔口服给予高达 681 mg/kg 体重/天的剂量，D-樟脑未显示出致畸性证据。大鼠胎儿机体的未观察到影响水平高于 1000 mg/kg 体重，家兔高于 681 mg/kg 体重。在大鼠母鼠中，从 464 mg/kg 体重/口服给药起，观察到食物摄入量和唾液分泌呈剂量依赖性减少。口服 1000 mg/kg 体重/天的高剂量导致明显的毒性迹象，如阵挛性惊厥、竖毛、活动减少和体重增加减少。在家兔母兔中，口服 681 mg/kg 体重/天的高剂量导致体重增加和食物消耗减少。在任何处理剂量水平，甚至在最高测试剂量水平（大鼠：1000 mg/kg 体重/口服给药；家兔：681 mg/kg 体重/口服给药），均未观察到变异、发育迟缓或畸形的发生率增加。人类每日最大樟脑治疗剂量约为 1.43 mg/kg 体重。因此，在当前测试条件下，反映安全范围较宽的胚胎毒性终点的治疗指数高于 450。
