Distribution of bisphenol A in the neuroendocrine organs of female rats

Abstract

The distribution of 14C-bisphenol A (BPA) in plasma and neuroendocrine organs was determined in Fischer 344 female rats following three oral doses (0.1, 10 or 100mg/kg). Plasma and tissue maximum concentrations (Cmax) were reached within 15-30 min of dosing. Plasma areas-under-the-curve (AUC) ranged from 0.06 to 53.9 microg-h/mL. The AUCs of the pituitary gland and uterus/gonads were 16-21% higher than that of plasma. The AUCs of hypothalamus and the rest of the brain were 43.7% and 77% of the plasma AUCs, respectively. In the brain tissue, the exposure increased linearly with the oral dose, as the dose was increased from 0.1 to 10 and 100 mg/kg; the exposure in the brain relative to the plasma increased by factors of 1, 1.19 and 1.24. This indicates that the brain barrier systems do not limit the access of the lipophilic BPA to the brain. The increases of the uterus/gonads relative to the plasma were 1, 1.07 and 1.04. Tissue partitioning was also examined in vitro by the uptake of 14C-BPA. The BPA tissue/blood partition coefficients were as follows: heart, 7.5; liver, 6.1; kidney, 6.4; fat, 3.6; muscle, 2.6; breast, 3.6; ovaries, 9.1; uterus, 5.9; stomach, 5.1; and small intestine, 6.7. The tissue/cerebrospinal fluid partition coefficients were as follows: pituitary gland, 12.8; brain stem, 6.1; cerebellum, 6.4; hippocampus, 7.1; hypothalamus, 6.1; frontal cortex, 4.9; and caudate nucleus, 6.8.

Conjugation and Deconjugation Reactions within the Fetoplacental Compartment in a Sheep Model: A Key Factor Determining Bisphenol A Fetal Exposure

“…The conjugation/deconjugation balance was clearly in favor of BPA-G deconjugation in ovine fetal gonads (ovaries and testes) with an activity of BPA-G hydrolysis 10-fold higher than the activity of BPA conjugation. As the total BPA levels in adult rodent gonads exceeded those in plasma (Yoo et al, 2000;Zalko et al, 2003;Kim et al, 2004), the capacity of gonads to hydrolyze BPA-G could lead to a reactivation of BPA directly at the level of target tissues. The close proximity of both the enzymes responsible for the formation (UGT) as well as the hydrolysis (b-glucuronidase) of BPA-G could result in a cycle of glucuronidation and deglucuronidation.…”

Estrogenic Endocrine Disrupting Chemicals Influencing NRF1 Regulated Gene Networks in the Development of Complex Human Brain Diseases

“…There is evidence to suggest BPA is released from plastic bottles used to store beverages consumed by consumers, with BPA migration increasing with exposure to heat [63]. Animal studies have indicated the ability BPA to penetrate the blood brain barrier due to its lipophilic nature [64,65]. …”

“…However, PCBs, BPA, phthalates, Cd, As or Mn, through influencing gonadotropin-releasing hormone (GnRH) regulated increases in levels of serum LH and E2, have been shown to modify the hypothalamic–pituitary-ovarian axis and they also bind to estrogen receptors [1,2,149,173]. BPA, Phthalates and metalloestrogens—Cd, As and Mn have been shown to cross the blood brain barrier [1,64,65,118,119,149,173]. Metalloestrogens, such as arsenite, cadmium, mimic the actions of physiological estrogens through binding to estrogen receptors [196,197,198].…”

Prenatal exposure to bisphenol A interferes with the development of cerebellar granule neurons in mice and chicken

“…Exposure measurement data from several countries indicate that humans are widely exposed to low levels of BPA on a continuous basis (vom Saal and Hughes, 2005). BPA passes through the blood-brain barrier and the BPA brain tissue content in rat was 18-41% of that in plasma (Kim et al, 2004). BPA also passes through the placenta (Schonfelder et al, 2002) and has been detected in the human amniotic fluid (Ikezuki et al, 2002), indicating significant fetal exposure.…”