Effects of Thiocyanate on Fetal and Postnatal Development and Thyroid Function in Rats.

Human exposures to thiocyanate through dietary intake and tobacco smoking are extensive. This compound has antithyroid activity in adults, but the effects of thiocyanate in developing organisms have not been extensively studied. Therefore, research was undertaken in rats to investigate the effects of thiocyanate on: (1) embryonic, fetal and neonatal development; and (2) hypothalamic-pituitary-thyroid axis development. Thiocyanate did not cause significant teratogenicity but did cause fetal growth retardation when administered at 55 and 220 mg/kg on gestational days 6-15. Thiocyanate administration throughout gestation (150/mg/kg/day) also retarded postnatal growth and development. Continued exposure throughout lactation worsened this retardation only slightly. This suggests that thiocyanate impaired postnatal development by interfering with cellular processes primarily during the prenatal period. This phenomenon may be explained by the toxicokinetics of thiocyanate in fetuses and neonates. Thiocyanate peaked at 10.7 mg% in fetal plasma after maternal dosing. In contrast, thiocyanate never exceeded 1.2 mg% in neonatal serum. The relatively low thiocyanate concentrations in these pups may account for the minimal retardation. Thiocyanate exposure during gestation did not significantly alter postnatal serum levels of pituitary and thyroid hormones. Continued thiocyanate administration throughout lactation resulted in significant hormone changes after the compound was withdrawn. On the 56th postnatal day, serum thyroid hormones were elevated and thyrtotropin was decreased. By day 91, thyrotropin was depressed even further, and thyroid hormones returned to normal in most animals. Analysis of the data indicates that the observed hyperthyroidism may have resulted from: (1) hypersensitivity of the thyroid to thyrotropin; and (2) insufficient suppression of thyrotropin secretion by the pituitary in response to elevated thyroid hormone concentrations. The postnatal serum thiocyanate levels required to produce these effects in rat pups were near those observed in babies born to smoking mothers. In addition, the toxicokinetics of thiocyanate in neonatal rats closely resembles the pattern observed in humans. Taken together, these data indicate a potential for thiocyanate to cause long term hypothalamic-pituitary-thyroid axis alterations in human offspring.PhDPublic healthUniversity of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/160146/1/8422250.pd