title: Aromatase inhibiting and combined estrogenic effects of parabens and estrogenic effects of other additives in cosmetics.
abstract: There is concern widely on the increase in human exposure to exogenous (anti)estrogenic compounds. Typical are certain ingredients in cosmetic consumer products such as musks, phthalates and parabens. Monitoring a variety of human samples revealed that these ingredients, including the ones that generally are considered to undergo rapid metabolism, are present at low levels. In this in vitro research individual compounds and combinations of parabens and endogenous estradiol (E(2)) were investigated in the MCF-7 cell proliferation assay. The experimental design applied a concentration addition model (CA). Data were analyzed with the estrogen equivalency (EEQ) and method of isoboles approach. In addition, the catalytic inhibitory properties of parabens on an enzyme involved in a rate limiting step in steroid genesis (aromatase) were studied in human placental microsomes. Our results point to an additive estrogenic effect in a CA model for parabens. In addition, it was found that parabens inhibit aromatase. Noticeably, the effective levels in both our in vitro systems were far higher than the levels detected in human samples. However, estrogenic compounds may contribute in a cumulative way to the circulating estrogen burden. Our calculation for the extra estrogen burden due to exposure to parabens, phthalates and polycyclic musks indicates an insignificant estrogenic load relative to the endogenous or therapeutic estrogen burden.
authors.affiliation: Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, The Netherlands. J.A.vanMeeuwen@iras.uu.nl
authors.forename: J A
authors.initials: JA
authors.lastname: van Meeuwen
authors.forename: O
authors.initials: O
authors.lastname: van Son
authors.forename: A H
authors.initials: AH
authors.lastname: Piersma
authors.forename: P C
authors.initials: PC
authors.lastname: de Jong
authors.forename: M
authors.initials: M
authors.lastname: van den Berg
mesh_terms: D047072:Aromatase Inhibitors / Q000009:adverse effects*; D002384:Catalysis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003358:Cosmetics / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008861:Microsomes / Q000201:enzymology; D010226:Parabens / Q000009:adverse effects*; D010920:Placenta / Q000201:enzymology; D011310:Preservatives, Pharmaceutical / Q000009:adverse effects*
chemical_list: D047072:Aromatase Inhibitors; D003358:Cosmetics; D004967:Estrogens; D010226:Parabens; D011310:Preservatives, Pharmaceutical