Carbendazim-induced alterations of reproductive development and function in the rat and hamster.
We are developing a data base that will allow us to select endpoints that would be useful in the detection of reproductive toxicity in a multigenerational test. In this effort, carbendazim (MBC), a known reproductive toxicant, was administered to male and female rats from weaning, through puberty, gestation, and lactation. A similar study was conducted with hamsters. In rats, MBC was administered at 0, 50, 100, 200, or 400 mg/kg/day. Hamsters were dosed at 0 or 400 mg/kg/day. In the parent (P0) generation, landmarks of puberty were measured. In females, estrous cyclicity, litter size, the number of implants, organ weights, and histology were assessed. Our assessment of the male rat included organ weights, testicular and epididymal sperm counts, a quantitative measure of sperm motility, sperm morphology, testicular histology, and endocrine measures. The growth, viability, and reproductive function of the offspring (F1) were observed during a 4-month period of continuous breeding. In the P0 of both species. MBC did not alter pubertal development, growth, or viability. The reproductive potential of the rats treated with MBC at 200 and 400 mg/kg/day was reduced due to effects on sperm production and fetal viability. In the male rat, MBC treatment markedly altered sperm morphology, testicular and epididymal weights, and sperm numbers and testicular histology. Fertility, sperm motility, and hormonal levels were altered, primarily in the males with very low sperm counts. The ability to conceive did not appear to involve a female factor. In P0 female rats, MBC administration caused postimplantation losses in the high-dosage groups and a few malformed rat pups were found in the litters from the 100 and 200 treatment groups. MBC was less toxic to the hamster than the rat. The only reproductive effects induced by MBC treatment were on sperm measures. Fertility of the P0 generation and fetal and neonatal (F1) viability were not decreased by MBC administration. In the male rat, testis weight, sperm numbers in the cauda epididymis and testis and sperm morphology were sensitive to the effects of MBC. In females, counting implantation scars at necropsy was useful, as this information allowed us to confirm pregnancy and identify postimplantation losses induced by MBC administration.
Gray
L E
LE
Developmental Reproductive Biology Section, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
Ostby
J
J
Linder
R
R
Goldman
J
J
Rehnberg
G
G
Cooper
R
R
D000818:Animals; D001562:Benzimidazoles / Q000633:toxicity*; D001724:Birth Weight / Q000187:drug effects; D002219:Carbamates; D006224:Cricetinae; D005260:Female; D005659:Fungicides, Industrial / Q000633:toxicity*; D008297:Male; D008647:Mesocricetus; D010907:Pituitary Hormones / Q000378:metabolism; D012098:Reproduction / Q000187:drug effects*; D012726:Sexual Behavior, Animal / Q000187:drug effects; D012741:Sexual Maturation / Q000187:drug effects*; D013045:Species Specificity; D013076:Sperm Count; D013081:Sperm Motility / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects / Q000648:ultrastructure
D001562:Benzimidazoles; D002219:Carbamates; D005659:Fungicides, Industrial; D010907:Pituitary Hormones; C006698:carbendazim