The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings may not have been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009. For more information, see the Explanation of Levels of Evidence for Developmental Toxicity. The findings and conclusions for this study should not be construed to represent the views of NTP or the U.S. Government.
Scopolamine hydrobromide, a naturally occurring anitcholinergic drug, was evaluated for toxic and teratogenic effects in timedpregnant CD-1 mice. Animals were exposed to SCOP in water, by gavage on gestational days 6 through 15 and sacrificed on gd 17. Prior to initiation of the teratology study, a preliminary study was conducted in order to establish appropriate doses for use in the teratology study. Based on the results of the preliminary study, doses of 0, 10, 100, 450, or 900 mg/kg/day SCOP were administered in the teratology study.
The teratology study was conducted using a three-replicate design, with 10-17 animals assigned to each dose group in each replicate. In each replicate, females were weighed and observed during daily treatment for clinical signs of toxicity. At sacrifice on gd 17, the gravid uterus of each dam was weighed. Following uterine dissection the number and status of uterine implantation sites was recorded. Each live fetus was weighed, sexed, and examined for external, visceral, and skeletal malformations. A total of 23-32 dams (i.e., confirmed-pregnant females) per treatment group were evaluated in the study.
Exposure of timed-pregnant CD-1 mice to SCOP dissolved in distilled water and administered by gavage at doses of 0, 10, 100, 450, or 900 mg/kg/day on gd 6-15 produced the following results:
- A no effect level for maternal and fetal toxicity at doses of 10 and 100 mg/kg/day.
- Marginal maternal toxicity, observed as slightly reduced maternal body weight and weight gain determined at the 450 and 900 mg/kg/day doses, with corrected maternal body weight significantly reduced at 900 mg/kg/day.
- A marginal reduction in average fetal body weight per litter at 450 and 900 mg/kg/day.
- Congenital malformations and anatomical variations were observed, at low levels, in all groups. There was no relationship seen between their occurrence and the level of treatment and they were seen with equal frequency throughout the groups studied. Because of this, scopolamine had no observable effect on any measure of embryotoxicity at any dose level.
In conclusion, SCOP administered to pregnant CD-1 mice during the period of major organogenesis at doses up to 900 mg/kg/day had no adverse effect on prenatal viability, produced no evidence of teratogenesis, and caused only a marginal reduction in fetal body weight at doses of 450 and 900 mg/kg/day, that also caused marginal maternal toxicity.