Developmental effects of methyl benzimidazolecarbamate following exposure during early pregnancy.
Methyl 2-benzimidazolecarbamate (MBC) and its parent compound benomyl are used as agricultural fungicides. Both chemicals are embryotoxic if administered during organogenesis, and benomyl is teratogenic. Based on a previous study indicating a lack of maternal effects of MBC following exposure during early pregnancy, the current experiments were designed to evaluate the effect of exposure to MBC during early pregnancy on developmental parameters of offspring. Rats were administered MBC at 0, 100, 200, 400, or 600 mg/kg/day during Days 1-8 of pregnancy and killed on Day 11 or Day 20 of gestation. On Day 11, embryos were assessed for survival rate, growth parameters, and anomalies. On Day 20, standard developmental toxicity evaluations were performed. Doses of 200 to 600 mg/kg/day MBC reduced embryonic survival by Day 11; exposure to MBC at 100 to 600 mg/kg/day reduced the number of fetuses surviving on Day 20. Evidence of developmental delay was apparent on Day 11 at all doses, and fetal weight was reduced by Day 20. MBC produced a dose-dependent increase in developmental defects seen on Day 11 and in several malformations observed on Day 20. MBC exposure during the first week of pregnancy was shown to be embryotoxic, resulting in embryonic death, growth retardation, and developmental abnormalities when evaluated on Days 11 or 20 of gestation.
Cummings
A M
AM
Developmental Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
Ebron-McCoy
M T
MT
Rogers
J M
JM
Barbee
B D
BD
Harris
S T
ST
D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000818:Animals; D001562:Benzimidazoles / Q000633:toxicity*; D001842:Bone and Bones / Q000002:abnormalities; D002219:Carbamates; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian / Q000187:drug effects; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D005313:Fetal Death / Q000139:chemically induced; D005327:Fetal Resorption / Q000139:chemically induced; D005659:Fungicides, Industrial / Q000633:toxicity*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects*; D011297:Prenatal Exposure Delayed Effects; D051381:Rats
D001562:Benzimidazoles; D002219:Carbamates; D005659:Fungicides, Industrial; C006698:carbendazim