Endocrine-disrupting potential of bisphenol A, bisphenol A dimethacrylate, 4-n-nonylphenol, and 4-n-octylphenol in vitro: new data and a brief review.
BACKGROUND
An array of environmental compounds is known to possess endocrine disruption (ED) potentials. Bisphenol A (BPA) and bisphenol A dimethacrylate (BPA-DM) are monomers used to a high extent in the plastic industry and as dental sealants. Alkylphenols such as 4-n-nonylphenol (nNP) and 4-n-octylphenol (nOP) are widely used as surfactants.


OBJECTIVE
We investigated the effect in vitro of these four compounds on four key cell mechanisms including transactivation of a) the human estrogen receptor (ER), b) the human androgen receptor (AR), c) the aryl hydrocarbon receptor (AhR), and d) aromatase activity.


RESULTS
All four compounds inhibited aromatase activity and were agonists and antagonists of ER and AR, respectively. nNP increased AhR activity concentration-dependently and further increased the 2,3,7,8-tetrachlorodibenzo-p-dioxin AhR action. nOP caused dual responses with a weak increased and a decreased AhR activity at lower (10(-8) M) and higher concentrations (10(-5)-10(-4) M), respectively. AhR activity was inhibited with BPA (10(-5)-10(-4) M) and weakly increased with BPA-DM (10(-5) M), respectively. nNP showed the highest relative potency (REP) compared with the respective controls in the ER, AhR, and aromatase assays, whereas similar REP was observed for the four chemicals in the AR assay.


CONCLUSIONS
Our in vitro data clearly indicate that the four industrial compounds have ED potentials and that the effects can be mediated via several cellular pathways, including the two sex steroid hormone receptors (ER and AR), aromatase activity converting testosterone to estrogen, and AhR; AhR is involved in syntheses of steroids and metabolism of steroids and xenobiotic compounds.
Bonefeld-Jørgensen
Eva C
EC
Unit of Cellular and Molecular Toxicology, Institute of Public Health, Department of Environmental and Occupational Medicine, University of Aarhus, Aarhus, Denmark. ebj@mil.au.dk
Long
Manhai
M
Hofmeister
Marlene V
MV
Vinggaard
Anne Marie
AM
D000818:Animals; D001141:Aromatase / Q000187:drug effects* / Q000378:metabolism; D001559:Benzhydryl Compounds; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000008:administration & dosage / Q000633:toxicity*; D006801:Humans; D066298:In Vitro Techniques; D008689:Methacrylates / Q000008:administration & dosage / Q000633:toxicity; D010636:Phenols / Q000008:administration & dosage / Q000633:toxicity; D011944:Receptors, Androgen / Q000187:drug effects* / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects* / Q000378:metabolism; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000378:metabolism; D000098826:Bisphenol A Compounds
D001141:Aromatase; D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D008689:Methacrylates; D010636:Phenols; D011944:Receptors, Androgen; D018336:Receptors, Aryl Hydrocarbon; D011960:Receptors, Estrogen; C080417:4-octylphenol; C002462:4,4'-isopropylidenediphenol dimethacrylate; D000098826:Bisphenol A Compounds; C041594:4-nonylphenol; C006780:bisphenol A