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© 1995 Oxford University Press

research-article

The Adverse Effects of Oral 2-Mercaptobenzimidazole on Pregnant Rats and Their Fetuses

TETSUO YAMANO1, TSUTOMU NODA, MITSURU SHIMIZU and SHIGERU MORITA

Osaka City Institute of Public Health and Environmental Sciences 8-34 Tojo-cho, Tennoji-ku, Osaka 543, Japan

Received July 5, 1994; accepted September 28, 1994

The effects of oral 2-mercaptobenzimidazole (2-MBI) on pregnant Wistar rats were examined. In a preliminary dose-finding study, pregnant rats treated with 2-MBI over Days 7–17 of gestation showed reduction in maternal thymus weights with compound-related mortality at doses≥40 mg/kg. No adverse effects on fetuses were found at doses ≤40 mg/kg. However, anasarca, cleft palate, and dilated lateral ventricles were present in all fetuses from the only survivor among the dams treated with 60 mg/kg of 2-MBI. In the teratology study, pregnant rats were treated with 2-MBI at doses of 0, 3.3, 10, and 30 mg/kg during the period of organogenesis (Gestation Days 7–17). In addition, pregnant rats of three groups were also treated with 60 mg/kg of 2-MBI for 3 or 4 days during specific periods of organogenesis (Days 7–10, 11–14, or 15–17 of gestation). Treatment on Gestation Days 7–17 resulted in reduced maternal thymus weights at doses of ≥3.3 mg/kg. In addition to reduced fetal weights, visceral variations (kinked ureter and dilated renal pelvis) and delayed ossification were seen in the fetuses at doses ≥10 mg/kg, and skeletal variations (rudimentary lumbar ribs) were seen at 30 mg/kg. In the fetuses from the dams treated with 60 mg/kg of 2-MBI, rudimentary lumbar ribs were seen mainly in the group treated on Days 7/10 of gestation, whereas kinked ureter and dilated renal pelvis were evident mainly in the group treated on Gestation Days 15/17. Dilated lateral ventricles and cleft palate were present only in the group treated with 60 mg/kg on Days 11–14 of gestation, though 5 out of 16 dams died during the study. In conclusion, maternal toxicity preceded fetal toxicity and major fetal malformations were seen only at a dose (60 mg/kg) which was lethal to many of the treated dams.


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