Estrogenic effects of mixtures of phyto- and synthetic chemicals on uterine growth of prepubertal rats.
Through the diet humans are exposed to many weak estrogenic phytochemicals (PCs) and synthetic chemicals (SCs), but most experimental studies used individual compounds rather than mixtures. Estrogenic effects were determined in the rat juvenile uterotrophic assay using a predefined phytochemical mixture (PCmix) containing coumestrol, genistein, naringenin, (+,-)catechin, (-,-)epicatechin and quercetin, and a predefined synthetic chemical mixture (SCmix) containing nonyl-, and octylphenol, beta-hexachlorocyclohexane, methoxychlor, bisphenol A and dibutylphthalate. The mixture composition was based on human dietary uptake and actual ratios in serum. 17beta-Estradiol and genistein were also tested individually. It was found that combinations of phytoestrogens and exogenous 17beta-estradiol act additive. In contrast SCmix, inactive by itself even at high dose levels relative to human exposure, caused no synergistic or antagonistic uterotrophic effect with E(2) and/or the PCmix. Based on ED(05) and ED(01) values of the PCmix the margin of exposure in regular human diet for a uterotrophic effect is estimated many orders of magnitude. However, food supplements with phytochemicals might bring individual exposure around ED(05) and ED(01) values of the PCmix. Based on the results of our study the contribution of SCs to total estrogenicity in human diet can probably be neglected.
van Meeuwen
J A
JA
Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands. J.A.vanMeeuwen@iras.uu.nl <J.A.vanMeeuwen@iras.uu.nl>
van den Berg
M
M
Sanderson
J T
JT
Verhoef
A
A
Piersma
A H
AH
D000818:Animals; D001681:Biological Assay; D045424:Complex Mixtures / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007279:Injections, Subcutaneous; D009929:Organ Size / Q000187:drug effects; D048789:Phytoestrogens / Q000494:pharmacology*; D051381:Rats; D012741:Sexual Maturation; D014599:Uterus / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology; D015262:Xenobiotics / Q000494:pharmacology*
D045424:Complex Mixtures; D048789:Phytoestrogens; D015262:Xenobiotics