Distribution and unspecific protein binding of the xenoestrogens bisphenol A and daidzein

Abstract

Physiological toxicokinetic (PT) models are used to simulate tissue burdens by chemicals in animals and humans. A prerequisite for a PT model is the knowledge of the chemical's distribution among tissues. This depends on the blood flow and also on the free fraction of the substance and its tissue:blood partition coefficients. In the present study we determined partition coefficients in human tissues at 37 degrees C for the two selected xenoestrogens bisphenol A (BA) and daidzein (DA), and their unspecific binding to human serum proteins. Partition coefficients were obtained by incubating blood containing BA or DA with each of the following tissues: brain, liver, kidney, muscle, fat, placenta, mammary gland, and adrenal gland. Blood samples were analysed by HPLC. For BA and DA, all partition coefficients in non-adipose tissues were similar (average values: BA 1.4, DA 1.2). However, the lipophilic properties of both compounds diverge distinctly. Fat:blood partition coefficients were 3.3 (BA) and 0.3 (DA). These values indicate that with the exception of fat both compounds are distributed almost equally among tissues. In dialysis experiments, the unspecific binding of BA and DA with human serum proteins was measured by HPLC. For BA, the total concentration of binding sites and the apparent dissociation constant were calculated as 2000 and 100 nmol/ml, respectively. Because of the limited solubility of DA, only the ratio of the bound to the free DA concentration could be determined and was found to be 7.2. These values indicate that at low concentrations only small percentages of about 5% (BA) and 12% (DA) are as unbound free fractions in plasma. Since only the unbound fraction can bind to the estrogen receptor, binding to serum proteins represents a mechanism that limits the biological response in target tissues.

Urinary Bisphenol A (BPA) Concentrations among Workers in Industries that Manufacture and Use BPA in the USA

“…BPA is moderately lipophilic (Staples et al , 1998). In in vitro studies, human adipose tissue had the highest BPA concentration (Csanády et al , 2002; Geens et al , 2012). Thus, BPA storage in fat under certain conditions may be biologically plausible.…”

Bisphenol A in Chronic Kidney Disease

“…However, Krieter et al [33] showed that considerable amounts of BPA were eluted from dialyzers with polysulfone membranes in 180 min of simulating (in vitro) dialysis conditions with sterile water at body temperature. Previous studies had already shown that diferent polysulfone membranes leach varying amounts of BPA [31][32][33][34][35][36][37]. Obviously, this is also true for polysulfone membranes from the same manufacturer, indicating variations in diferent polysulfone lots or diferent extraction processes during iber spinning.…”

“…Moreover, a tissue/blood partition coeicient of 1.4 for nonadipose tissues and 3.3 for fat tissues further compromises the dialyzability of BPA [36], implying a concentration gradient highly in favor of driving BPA from dialysate to patient's blood.…”

The Adverse Cardiac Effects of Di(2-ethylhexyl)phthalate and Bisphenol A

“…The bound or inactive form of BPA represents 90–95% of total BPA in the blood 137–139 , whereas 80% of total DEHP is bound to lipoproteins and albumin 140–142 . Since many in vitro and ex vivo studies are conducted in serum-free or low albumin-containing solutions, additional studies are warranted to determine whether protein binding diminishes the bioavailability of these chemicals to such an extent that cardiotoxicity is irrelevant.…”