title: Endocrine disrupting effects in rats perinatally exposed to a dietary relevant mixture of phytoestrogens.
abstract: Dietary phytoestrogens may prevent certain human diseases, but endocrine activity has been reported in animal studies. Sprague-Dawley rats were exposed perinatally to a 1-, 10- or 100-fold "high human dietary intake" mixture of 12 phytoestrogens consisting of mainly the lignan secoisolarici resinol and the isoflavones genistein and daidzein. This mixture induced persistent adverse effects, as adult male mammary glands showed hypertrophic growth. A reduced anogenital distance in newborn males indicated an anti-androgenic mode of action. Testosterone levels, testis and prostate weights, and expression of selected genes in testis and prostate were unaffected. Decreased serum estradiol was seen in genistein-exposed dams. This study indicated adverse effects at high intake levels in rats, but does not provide evidence for risk of phytoestrogen-mediated endocrine disruption at normal human dietary consumption levels. Further studies are warranted to increase the knowledge upon which risk assessment on dietary phytoestrogen exposure during pregnancy and infancy is based.
authors.affiliation: Division of Toxicology and Risk Assessment, National Food Institute, Technical University of Denmark, Søborg, Denmark. jubo@food.dtu.dk
authors.forename: Julie
authors.initials: J
authors.lastname: Boberg
authors.forename: Karen Riiber
authors.initials: KR
authors.lastname: Mandrup
authors.forename: Pernille Rosenskjold
authors.initials: PR
authors.lastname: Jacobsen
authors.forename: Louise Krag
authors.initials: LK
authors.lastname: Isling
authors.forename: Niels
authors.initials: N
authors.lastname: Hadrup
authors.forename: Line
authors.initials: L
authors.lastname: Berthelsen
authors.forename: Anders
authors.initials: A
authors.lastname: Elleby
authors.forename: Maria
authors.initials: M
authors.lastname: Kiersgaard
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Vinggaard
authors.forename: Ulla
authors.initials: U
authors.lastname: Hass
authors.forename: Christine
authors.initials: C
authors.lastname: Nellemann
mesh_terms: D001003:Anal Canal / Q000187:drug effects* / Q000254:growth & development; D000818:Animals; D004032:Diet; D052244:Endocrine Disruptors / Q000633:toxicity*; D005260:Female; D005835:Genitalia / Q000187:drug effects* / Q000254:growth & development; D007774:Lactation; D008297:Male; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology; D048789:Phytoestrogens / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D052244:Endocrine Disruptors; D048789:Phytoestrogens
keywords: 7,12-dimethylbenz(a)anthracene; AGD; Anti-androgenic; DMBA; Daidzein; Diet; GD; Genistein; Histology; Lignans; MNU; Mammary; N-nitroso-N-methylurea; PND; SECO; Secoisolarici resinol; TEB; anogenital distance; gestation day; postnatal day; secoisolariciresinol; terminal end bud