Teratogenicity of ethylenethiourea and thyroid function in the rat

Abstract

Ethylenethiourea (ETU) was given by gavage at a dose of 40 mg/kg/day from Days 7 through 15 of gestation to hypothyroid and euthyroid rats, and to rats given exogenous thyroxine, to determine whether ETU teratogenicity occurs through alteration of maternal thyroid function. At sacrifice on Day 20 of gestation 84-100% of the fetuses in all groups given ETU were malformed regardless of the thyroid status of the dams. Ten percent of the fetuses of dams thyroparathyroidectomized at 75 days of age that were not given ETU were malformed; no malformations were noted among the fetuses of the other groups not given ETU. Hence, ETU was found to induce teratogenicity in rats but not through alteration of maternal thyroid status. In addition, it was determined that ETU lowered serum thyroxine concentration, that hypothyroidism itself increased the background level of malformations in the rat, and that hypothyroidism qualitatively and quantitatively increased the incidence of specific malformations after ETU administration.