Concentrations of bisphenol A and estradiol are elevated by exposure to endocrine-disrupting chemicals

Abstract

Endocrine-disrupting chemicals (EDCs) are synthetic substances that perturb estrogen, androgen, and thyroid systems, thereby impacting development, reproduction, behaviour, and general health. People are concurrently exposed to numerous EDCs from diverse sources, including consumer products, personal care products, medical devices, and environmental media. I explored impacts of [1] triclosan (a synthetic biocide), [2] butyl paraben and [3] propyl paraben (antimicrobial preservatives), and [4] tetrabromobisphenol A (a flame retardant) on bisphenol A (BPA) and 17β-estradiol (E2) concentrations in vivo. I developed a novel protocol that measured acute effects of these four EDCs upon radiolabeled 14C-BPA or 3H-E2 in blood serum and tissues, and natural E2 in urine. First I showed that BPA, the monomer of polycarbonate plastics, localizes to the reproductive organs of female mice following low-dose dietary exposure. Subsequently, I demonstrated that exposure to any one of the four EDCs elevated 14C-BPA concentrations in blood serum, reproductive organs, and other peripheral tissues of female and male mice. Such exposure also elevated concentrations of natural E2 in urine. Finally, I showed that concurrent exposure to all four EDCs, in addition to diethylhexyl phthalate (a plasticizer), can elevate concentrations of 14C-BPA and E2 at much lower doses than required when given alone. These data show that endocrine-disrupting chemicals interact in vivo, and that they can modulate the toxicokinetics of BPA and disrupt natural estrogen homeostasis. This is consistent with evidence that EDCs compete for access to enzymes that are critical for their metabolism and estrogen regulation, such as cytochrome p450, sulfotransferase, UDP-glucuronosyltransferase, and hydroxysteroid dehydrogenase. Given the detrimental reproductive and carcinogenic effects of persistently elevated estrogen activity, the findings of these studies emphasize the importance of further investigating adverse health outcomes of chemical mixtures. Furthermore, studies of multiple chemicals should be considered when assessing risk and determining regulatory exposure limits.