Overlapping but distinct effects of genistein and ethinyl estradiol (EE(2)) in female Sprague-Dawley rats in multigenerational reproductive and chronic toxicity studies.
Genistein and ethinyl estradiol (EE(2)) were examined in multigenerational reproductive and chronic toxicity studies that had different treatment intervals among generations. Sprague-Dawley rats received genistein (0, 5, 100, or 500 ppm) or EE(2) (0, 2, 10, or 50 ppb) in a low phytoestrogen diet. Nonneoplastic effects in females are summarized here. Genistein at 500 ppm and EE(2) at 50 ppb produced similar effects in continuously exposed rats, including decreased body weights, accelerated vaginal opening, and altered estrous cycles in young animals. At the high dose, anogenital distance was subtly affected by both compounds, and a reduction in litter size was evident in genistein-treated animals. Genistein at 500 ppm induced an early onset of aberrant cycles relative to controls in the chronic studies. EE(2) significantly increased the incidence of uterine lesions (atypical focal hyperplasia and squamous metaplasia). These compound-specific effects appeared to be enhanced in the offspring of prior exposed generations.
Delclos
K Barry
KB
National Center for Toxicological Research, Jefferson, AR 72079, USA. barry.delclos@fda.hhs.gov
Weis
Constance C
CC
Bucci
Thomas J
TJ
Olson
Greg
G
Mellick
Paul
P
Sadovova
Natalya
N
Latendresse
John R
JR
Thorn
Brett
B
Newbold
Retha R
RR
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D052244:Endocrine Disruptors / Q000633:toxicity*; D004714:Endometrial Hyperplasia / Q000139:chemically induced / Q000473:pathology; D004971:Estrus / Q000187:drug effects; D004997:Ethinyl Estradiol / Q000633:toxicity*; D005260:Female; D019833:Genistein / Q000633:toxicity*; D008098:Litter Size / Q000187:drug effects; D008679:Metaplasia; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects*; D012726:Sexual Behavior, Animal / Q000187:drug effects; D012741:Sexual Maturation / Q000187:drug effects; D013997:Time Factors; D014599:Uterus / Q000187:drug effects / Q000473:pathology; D014621:Vagina / Q000187:drug effects / Q000254:growth & development
D052244:Endocrine Disruptors; D004997:Ethinyl Estradiol; D019833:Genistein