Abstract
BACKGROUND: Emodin, a widely available herbal remedy, was evaluated for potential effects on pregnancy outcome. METHODS: Emodin was administered in feed to timedโmated SpragueโDawley (CD) rats (0, 425, 850, and 1700โppm; gestational day [GD] 6โ20), and Swiss Albino (CDโ1) mice (0, 600, 2500 or 6000โppm; GD 6โ17). Ingested dose was 0, 31, 57, and โผ80โ144โmg emodin/kg/day (rats) and 0, 94, 391, and 1005โmg emodin/kg/day (mice). Timedโmated animals (23โ25/group) were monitored for body weight, feed/water consumption, and clinical signs. At termination (rats: GD 20; mice: GD 17), confirmed pregnant dams (21โ25/group) were evaluated for clinical signs: body, liver, kidney, and gravid uterine weights, uterine contents, and number of corpora lutea. Fetuses were weighed, sexed, and examined for external, visceral, and skeletal malformations/variations. RESULTS: There were no maternal deaths. In rats, maternal body weight, weight gain during treatment, and corrected weight gain exhibited a decreasing trend. Maternal body weight gain during treatment was significantly reduced at the high dose. In mice, maternal body weight and weight gain was decreased at the high dose. CONCLUSIONS: Prenatal mortality, live litter size, fetal sex ratio, and morphological development were unaffected in both rats and mice. At the high dose, rat average fetal body weight per litter was unaffected, but was significantly reduced in mice. The rat maternal lowest observed adverse effect level (LOAEL) was 1700โppm; the no observed adverse effect level (NOAEL) was 850โppm. The rat developmental toxicity NOAEL was โฅ1700โppm. A LOAEL was not established. In mice, the maternal toxicity LOAEL was 6000โppm and the NOAEL was 2500โppm. The developmental toxicity LOAEL was 6000โppm (reduced fetal body weight) and the NOAEL was 2500โppm. Birth Defects Res B 71:89โ101, 2004. ยฉ 2004 WileyโLiss, Inc.