Developmental toxicity evaluation of emodin in rats and mice.
BACKGROUND
Emodin, a widely available herbal remedy, was evaluated for potential effects on pregnancy outcome.


METHODS
Emodin was administered in feed to timed-mated Sprague-Dawley (CD) rats (0, 425, 850, and 1700 ppm; gestational day [GD] 6-20), and Swiss Albino (CD-1) mice (0, 600, 2500 or 6000 ppm; GD 6-17). Ingested dose was 0, 31, 57, and approximately 80-144 mg emodin/kg/day (rats) and 0, 94, 391, and 1005 mg emodin/kg/day (mice). Timed-mated animals (23-25/group) were monitored for body weight, feed/water consumption, and clinical signs. At termination (rats: GD 20; mice: GD 17), confirmed pregnant dams (21-25/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 1700 ppm; the no observed adverse effect level (NOAEL) was 850 ppm. The rat developmental toxicity NOAEL was > or =1700 ppm. A LOAEL was not established. In mice, the maternal toxicity LOAEL was 6000 ppm and the NOAEL was 2500 ppm. The developmental toxicity LOAEL was 6000 ppm (reduced fetal body weight) and the NOAEL was 2500 ppm.
Jahnke
Gloria D
GD
Sciences International Inc., Alexandria, Virginia, USA. jahnke@niehs.nih.gov
Price
Catherine J
CJ
Marr
Melissa C
MC
Myers
Christina B
CB
George
Julia D
JD
D000014:Abnormalities, Drug-Induced; D000015:Abnormalities, Multiple / Q000139:chemically induced; D000821:Animal Feed; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004326:Drinking; D047108:Embryonic Development / Q000187:drug effects*; D004642:Emodin / Q000633:toxicity*; D004791:Enzyme Inhibitors / Q000633:toxicity*; D005260:Female; D020567:Fetal Weight / Q000187:drug effects; D008297:Male; D018811:Maternal Exposure; D051379:Mice; D008956:Models, Chemical; D009115:Muridae; D019055:No-Observed-Adverse-Effect Level; D011247:Pregnancy; D011270:Pregnancy, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D013723:Teratogens; D013997:Time Factors
D004791:Enzyme Inhibitors; D013723:Teratogens; D004642:Emodin