AbstractThe effects of three natural phenolic acids (caffeic, ferulic, and p‐coumaric) on the rat thyroid gland were examined in a 3‐week oral‐treatment study. Forty male Wistar albino rats, divided into groups of 10 rats each and fed iodine‐rich diet, were administered by gastrointestinal tube saline (control), caffeic acid, ferulic acid, or p‐coumaric acid at a dose level of 0.25 μmol/kg/day for 3 weeks. The mean absolute and relative thyroid weights in caffeic, ferulic, or p‐coumaric acid groups were significantly increased to 127 and 132%, 146 and 153%, or 189 and 201% compared to control value, respectively. Histological examination of the thyroids of p‐coumaric acid group revealed marked hypertrophy and/or hyperplasia of the follicles. Caffeic or ferulic groups showed slight to moderate thyroid gland enlargement. Thyroid lesions in p‐coumaric acid group were associated with significant increases in cellular proliferation as indicated by [3H]thymidine incorporation. In addition, the goitrogenic effect of p‐coumaric acid was further confirmed by significant decreases (50%) in serum tri‐iodothyronine (T3) and thyroxine (T4), and a parallel increase (90%) in serum thyroid stimulating hormone (TSH) compared to control group. These results indicate that administration of p‐coumaric acid at relatively high doses induces goiter in rats. © 2003 Wiley Periodicals, Inc. J Biochem Mol Toxicol 17:324–328, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10094