Effects of methyl benzimidazolecarbamate during early pregnancy in the rat

Abstract

Methyl 2-benzimidizolecarbamate (MBC), an agricultural fungicide, and its parent compound benomyl have adverse reproductive effects on male rats and exhibit embryotoxicity, including teratogenicity, when administered to rats during mid to late pregnancy. This study was designed to assess potential maternal effects of MBC during early pregnancy, to distinguish maternal from embryotoxic effects of the chemical, and to differentiate between early pregnancy failure and late embryonic loss. MBC was administered to rats by gavage at 0, 25, 50, 100, 200, 400, and 1000 mg/kg/day during Days 1 through 8 of pregnancy (Day 0 = sperm positive). A range of maternal and embryonic parameters was assessed following euthanasia on Day 9, including the number of implantation sites, body weight gain, uterine weight, implantation site size, and serum ovarian and pituitary hormones. In a separate experiment, pseudopregnant rats were administered 0 or 400 mg/kg/day MBC during Days 1–8, received bilateral uterine decidual induction on Day 4, and were killed on Day 9 at which time the decidual cell response was evaluated as a measure of uterine competency. When dosages of up to 400 mg/kg/day of MBC were administered during early pregnancy, the chemical had no significant effect on any measured parameter but a trend toward increased resorptions was evident. The 1000 mg/kg/day dosage of MBC produced reductions in body weight gain, implantation site weight, and serum LH and an increase in serum estradiol. When administered during pseudopregnancy, 400 mg/kg/day MBC partially reduced uterine decidual growth but affected no other parameter. The data show that dosages of MBC (up to and including 400 mg/kg/day) which are embryotoxic and teratogenic when administered to rats during late pregnancy do not produce pregnancy failure, adverse maternal effects other than a partial decidual growth inhibition, or evidence of embryotoxicity other than a trend toward increased resorptions when administered during very early pregnancy.