A mixture of five endocrine-disrupting chemicals modulates concentrations of bisphenol A and estradiol in mice

Chemosphere. 2018 Feb;193:321-328. doi: 10.1016/j.chemosphere.2017.11.030. Epub 2017 Nov 7.


Most people in developed countries are exposed to multiple endocrine-disrupting synthetic chemicals. We previously showed that a single dose of triclosan, tetrabromobisphenol A (TBBPA), butyl paraben, propyl paraben, or di(2-ethylhexyl) phthalate elevated concentrations of bisphenol A (BPA) in mice. Here we investigated whether concurrent exposure to lower doses of these five chemicals could modulate concentrations of bisphenol A (BPA) or the natural estrogen, 17β-estradiol (E2). CF1 mice were injected subcutaneously with 0.1 or 0.5 mg of one chemical, or a 0.5 mg mixture containing 0.1 mg of each of all five chemicals, then given dietary 50 μg kg-114C-BPA. The mixture elevated 14C-BPA concentrations in the lungs, muscle, uterus, ovaries, kidney, and blood serum of female mice. When administered alone, triclosan and TBBPA elevated 14C-BPA concentrations in the uterus, ovaries, and blood serum. In another experiment, CF1 mice were injected subcutaneously with the 0.5 mg mixture containing 0.1 mg of all five chemicals, then E2 was measured in urine 2-12 h later. The mixture elevated E2 at 8 h after injection in female mice. No treatments significantly altered concentrations of 14C-BPA or E2 in male mice. These data show that these endocrine-disrupting chemicals interact in vivo, magnifying one another's effects, consistent with inhibition of enzymes that are critical for estrogen metabolism. These findings highlight the importance of considering exposure to multiple chemicals when assessing health outcomes and determining regulatory exposure limits.

Keywords: Bisphenol A; Estradiol; Paraben; Phthalate; Tetrabromobisphenol A; Triclosan.

MeSH terms

  • Animals
  • Benzhydryl Compounds / metabolism*
  • Drug Interactions
  • Endocrine Disruptors / pharmacology*
  • Estradiol / metabolism*
  • Estrogens / pharmacology
  • Female
  • Kidney / metabolism
  • Lung / metabolism
  • Male
  • Mice
  • Ovary / metabolism
  • Parabens / pharmacology
  • Phenols / metabolism*
  • Phthalic Acids / pharmacology
  • Polybrominated Biphenyls / pharmacology
  • Triclosan / pharmacology


  • Benzhydryl Compounds
  • Endocrine Disruptors
  • Estrogens
  • Parabens
  • Phenols
  • Phthalic Acids
  • Polybrominated Biphenyls
  • Triclosan
  • Estradiol
  • phthalic acid
  • tetrabromobisphenol A
  • bisphenol A
  • propylparaben