Camphor is widely used as a constituent of over-the-counter medicaments marketed for the relief of muscle aches, nasal congestion, and discomfort from cold sores. Ingestion of camphor can cause severe toxicity in humans. Because of the large population at risk for CAM exposure during the manufacture or use of such products and because it readily crosses the placenta. CAM was evaluated as a possible developmental toxicant. Accordingly, CAM (0, 100, 400, or 800 mg/kg) was admistered daily by gavage to pregnant rats during the major period of organogenesis (gd 6-15). CAM, 800 mg/kg, was selected as the high dose in our study, since previous reports indicated that 1250 mg/kg/day CAM causes 90% maternal mortality. Dams were monitored for physical and clinical signs of toxicity, and the effect of CAM on fetal growth, viability, and external, visceral and skeletal malformations was assessed on gd 20.
There was no maternal mortality during the study. Absolute and relative liver weights exhibited a significant dose-related increase, but did not exceed 10% of control values in any individual group. Maternal toxicity consisted of alterations in food and water consumption (absolute and relative) and decreased weight gain during the treatment period. Food consumption was initially suppressed by both 400 and 800 mg/kg/day CAM. but recovered to control levels by the end of the treatment period. No effect on food consumption was seen at 100 mg/kg/day CAM. Unlike the dose-dependent effects of CAM on food intake, all three doses of CAM increased maternal water consumption during one or more of the following measurement periods (gd 6 to 9; gd 12 to 15; gd 15 to 18). Although maternal body weights in all treatment groups were within 5% of control values at all gestational ages, maternal weight gain during the treatment period in the 800 mg/kg/day group was significantly reduced.
Examination of the uterine contents revealed that CAM, even at 800 mg/kg/day, had no adverse effect on fetal growth, viability, or morphological development.
In summary, CAM does not affect fetal growth, viability, or morphological development at doses causing minor maternal toxicity.