Toxicological Sciences 57, 284-291 (2000)
Copyright © 2000 by the Society of Toxicology
Reproductive and Developmental Toxicology |
Evaluation of the Developmental Toxicity of Formamide in Sprague-Dawley (CD) Rats
Chemistry and Life Sciences, Research Triangle Institute, Post Office Box 12194, Research Triangle Park, North Carolina 277092194 * Developmental and Reproductive Toxicology Group, National Toxicology Program, National Institute of Environmental Health Sciences, Post Office Box 12233, Research Triangle Park, North Carolina 27709
Timed-pregnant CD® outbred albino Sprague-Dawley rats received formamide (50, 100, or 200 mg/kg/day) or vehicle (5 ml/kg deionized/distilled water, po) on gestational days (gd) 6 through 19. Maternal food and water consumption (absolute and relative), body weight, and clinical signs were monitored at regular intervals throughout gestation. At termination (gd 20), confirmed-pregnant females (2123 per group) were evaluated for clinical status and gestational outcome; live fetuses were examined for external, visceral, and skeletal malformations and variations. There were no maternal deaths and no dose-related clinical signs. At 200 mg/kg/day, maternal body weight on gd 20, weight gain, and gravid uterine weight were significantly decreased. Maternal weight gain, corrected for gravid uterine weight, liver weight (absolute or relative), and food and water consumption (absolute or relative), were not affected. Formamide did not affect prenatal viability or incidences of fetal malformations or variations. Average fetal body weight/litter was decreased at 100 and 200 mg/kg/day. Fetal body weight was affected at lower daily doses than in previously published studies, possibly due to the longer total exposure period and/or lack of a recovery period between cessation of exposure and termination. In summary, the maternal toxicity no-observed-adverse-effect level (NOAEL) was 100 mg/kg/day and the low observed adverse effect level (LOAEL) was 200 mg/kg/day under the conditions of this study. Similarly, the developmental toxicity NOAEL was 50 mg/kg/day and the LOAEL was 100 mg/kg/day.
Key Words: formamide; developmental toxicity; teratogenicity; rats; morphological development.
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