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. 2007 Dec;115 Suppl 1(Suppl 1):69-76.
doi: 10.1289/ehp.9368.

Endocrine-disrupting potential of bisphenol A, bisphenol A dimethacrylate, 4-n-nonylphenol, and 4-n-octylphenol in vitro: new data and a brief review

Eva C Bonefeld-Jørgensen  1 , Manhai Long, Marlene V Hofmeister, Anne Marie Vinggaard
Affiliations

Endocrine-disrupting potential of bisphenol A, bisphenol A dimethacrylate, 4-n-nonylphenol, and 4-n-octylphenol in vitro: new data and a brief review

Eva C Bonefeld-Jørgensen et al. Environ Health Perspect. 2007 Dec.

Abstract

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.

Objectives: 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.

Conclusion: 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.

Keywords: BPA; BPA-DM; androgenic; aromatase; endocrine disruption; estrogenic; nNP; nOP; nuclear receptors.

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Figures

Figure 1
Figure 1
Structures of the chemicals used in the present study.
Figure 2
Figure 2
Dose–response ER transactivation of E2 and the four test chemicals. (A) The MVLN cells were exposed to E2 in the concentration range of 0.05–500 pM and to the test chemicals at 10−8–10−4 M for 24 hr. Solvent control was set to 100%. E2 EC100 and EC50 as well as EC50 for each of the test chemicals were determined by Sigma Plot 8.0. (B) Agonistic and antagonistic ER activity of test chemicals BPA, BPA-DM, nNP, and nOP. The chemicals were tested alone or on co-exposure with 25 pM E2, which was set to 1. Mean values are shown (n ≥ 3). *Significantly different from the respective solvent controls (cells + 0.1% DMSO; 25 pM E2 + 0.1% DMSO).
Figure 3
Figure 3
AR antagonism of the test chemicals on co-exposure with R1881 in transient transfected CHO-K1 cells. Cells were transiently transfected with the AR expression pSVAR0 and the reporter pMMTV-LUC vector.
See this image and copyright information in PMC

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