The adverse effects of oral 2-mercaptobenzimidazole on pregnant rats and their fetuses.
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 > or = 40 mg/kg. No adverse effects on fetuses were found at doses < or = 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 > or = 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 > or = 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Yamano
T
T
Osaka City Institute of Public Health and Environmental Sciences, Japan.
Noda
T
T
Shimizu
M
M
Morita
S
S
D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000284:Administration, Oral; D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D001842:Bone and Bones / Q000002:abnormalities; D001921:Brain / Q000002:abnormalities; D002972:Cleft Palate / Q000139:chemically induced; D004435:Eating / Q000187:drug effects; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D007668:Kidney / Q000002:abnormalities; D008297:Male; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects*; D051381:Rats; D012272:Ribs / Q000002:abnormalities; D018675:Toxicity Tests; D014513:Ureter / Q000002:abnormalities
D001562:Benzimidazoles; C030698:2-mercaptobenzimidazole