Grant sponsor: NIH; Grant number: #1R01HD065200-01 (SAR).
Evaluation of Developmental Toxicity of Propylthiouracil and Methimazole
Article first published online: 30 JUN 2014
© 2014 Wiley Periodicals, Inc.
Birth Defects Research Part B: Developmental and Reproductive Toxicology
Volume 101, Issue 4, pages 300–307, August 2014
How to Cite
Mallela, M. K., Strobl, M., Poulsen, R. R., Wendler, C. C., Booth, C. J. and Rivkees, S. A. (2014), Evaluation of Developmental Toxicity of Propylthiouracil and Methimazole. Birth Defects Research Part B: Developmental and Reproductive Toxicology, 101: 300–307. doi: 10.1002/bdrb.21113
- Issue published online: 13 AUG 2014
- Article first published online: 30 JUN 2014
- Manuscript Accepted: 5 MAY 2014
- Manuscript Received: 13 MAR 2014
- NIH. Grant Number: #1R01HD065200-01
- antithyroid drugs;
- developmental toxicity
Propylthiouracil (PTU) and methimazole (MMI) are antithyroid drugs used to treat hyperthyroidism. Despite the widespread use of PTU and MMI during pregnancy, modest clinical data and less animal data are available on the teratogenic potential of these drugs.
We evaluated the teratogenicity of in utero exposure to PTU or MMI in mice and rats. First, pregnant C57Bl/6 mice were treated daily with PTU (10 or 100 mg/kg), MMI (2 or 20 mg/kg), or vehicle from gestation day (GD) 6 to 16. GD 18 fetuses were evaluated for gross and histopathological abnormalities. Next, pregnant Sprague-Dawley rats were treated daily with PTU (50 or 100 mg/kg), MMI (10 or 20 mg/kg), or vehicle from GD 6 to 19, followed by evaluation for gross and histopathological abnormalities at GD 20.
In mice treated with PTU or MMI, no significant histopathological abnormalities or external gross malformations, and no adverse effects on placental weight, litter size, resorption rates, or fetal weight were observed at GD 18. In rats, no adverse effects on litter size, placental weights, or maternal body weights were observed with either PTU or MMI treatment. PTU treatment (50 and 100 mg/kg) and MMI (10 mg/kg) treatment resulted in a decrease in crown-rump length in rat fetuses but no external gross malformations or histopathological abnormalities were observed.
We did not observe either gross external malformations or histopathological malformations in mice or rats treated long-term with high doses of PTU or MMI during pregnancy