Effects of Zinc 2-Mercaptobenzimidazolate on Pregnant Rats by Oral Treatment

Abstract

The effects of zinc 2-mercaptobenzimidadolate (ZMBI), which contains ethylene thiourea (ETU) in its structure and is used as an accelerator and/or antioxidant in rubber manufacturing, on pregnant Wistar rats, were examined. Moreover, the effects were compared with those of ETU. ZMBI was administered orally to pregnant rats during the period of organogenesis (days 7-17 of gestation) at doses of 0, 5, 15, and 45mg/kg/day. The treatment resulted in reduced maternal thymus weight and increased thyroid gland weight at doses of ≥ 5mg/kg and ≥ 15mg/kg, respectively. Reduced fetal weight and visceral variations (kinked ureter and dilated renal pelvis) were seen at doses of ≥ 15mg/kg, and skeletal variation (rudimentary lumber ribs) was observed at 45mg/kg. Teratological effects were not observed at doses used in the present study. Thus, the no-observed-adverse-effect level (NOAEL) for maternal toxicity was considered to be less than 5mg/kg/day, and that for fetal toxicity was 5mg/kg/day. Effects of ZMBI at a dose of 73mg/kg/day (200μmol/kg/day) were compared with those of ETU at a dose of 41mg/kg/day (400μmol/kg/day). In this experiment these compounds were administered to dams during the gestational periods of days 7-10, 11-14, or 15-17. The ZMBI treatment on days 11-14 of gestation caused fetal dilated lateral ventricles and cleft plate in about 30% of the fetuses. Kinked ureter and dilated renal pelvis were also observed mainly in this group. The same visceral variations were also observed in the group treated with ETU on days 11-14 of gestation. Although cleft palate was detected in the fetuses of the dams treated with ZMBI on days 11-14 of gestation, ETU treatment on days 11-14 of gestation caused exencephaly, hydrocephaly/hydrace-phaly and club foot which were not observed in any group treated with ZMBI. Thus, in the present investigations, different spectra of malformations by the chemically related compounds, ZMBI and ETU, were observed.