Elsevier

Reproductive Toxicology

Review

Human exposure to bisphenol A (BPA)☆

Abstract

The plastic monomer and plasticizer bisphenol A (BPA) is one of the highest volume chemicals produced worldwide. BPA is used in the production of polycarbonate plastics and epoxy resins used in many consumer products. Here, we have outlined studies that accost the levels of BPA in man tissues and fluids. We accept reviewed the few epidemiological studies bachelor that explore biological markers of BPA exposure and man wellness outcomes. We have examined several studies of levels of BPA released from consumer products besides equally the levels measured in wastewater, drinking water, air and grit. Lastly, we have reviewed acute metabolic studies and the data available most BPA metabolism in animate being models. The reported levels of BPA in human being fluids are college than the BPA concentrations reported to stimulate molecular endpoints in vitro and appear to be within an order of magnitude of the levels needed to induce effects in animal models.

Introduction

The plastic monomer and plasticizer bisphenol A (BPA) is ane of the highest volume chemicals produced worldwide, with over six billion pounds produced each year [1]. BPA is used in the production of polycarbonate plastics, epoxy resins used to line metal cans, and in many plastic consumer products including toys, h2o pipes, drinking containers, eyeglass lenses, sports safety equipment, dental monomers, medical equipment and tubing, and consumer electronics [2]. BPA has been shown to leach from nutrient and potable containers, and some dental sealants and composites under normal conditions of use. Studies have besides determined that BPA can exist measured in humans in serum, urine, amniotic fluid, follicular fluid, placental tissue, and umbilical string blood. In some cases, the levels of total BPA (costless and conjugated) in human blood and other fluids are higher than the concentrations that have been reported to stimulate a number of molecular endpoints in prison cell civilisation in vitro [3], and appear to be within an order of magnitude of the levels of BPA in fauna studies [4]; both of these literatures are reviewed in the papers of other panels of this coming together.

Biochemical assays have examined the kinetics of BPA binding to estrogen receptors (ER) and have determined that BPA binds both ERα and ERβ, with approximately 10-fold higher affinity to ERβ [five], [6], [7]. The affinity of BPA for ERs is ten,000–100,000-fold weaker than that of estradiol. Until recently, BPA had been considered to be a very weak environmental estrogen because of its low ER affinity and because in many bioassays (e.g., the rodent uterotrophic assay and some responses in homo breast cancer cells), BPA can be 10,000–100,000-fold less strong than estradiol. Withal, results from recent studies of molecular mechanisms of BPA activity have revealed a variety of pathways through which BPA can stimulate cellular responses at very low concentrations (reviewed in [8]) in addition to effects initiated past binding of BPA to the classical nuclear or genomic estrogen receptors. Recent findings show that in a variety of tissues, BPA not only has the efficacy of estradiol but is too every bit strong, with changes in cell function being observed at a dose of i   pM (0.23   pg/ml culture medium), through mechanisms that are thought to be non-genomic and involve membrane-associated forms of the estrogen receptors (reviewed in [3]).

"Low-doses" of endocrine disrupting chemicals were defined past the NIEHS Low Dose Peer Review every bit doses below the accustomed NOAEL for the chemical [9], which, for BPA, are doses below 50   mg/kg body weight/day. Initial reports of agin furnishings of BPA at "low-doses" in animal models were beneath the reference dose (RfD), calculated as an acceptable daily homo intake typically 1000-fold below the NOAEL. At that place are now over 150 published studies describing low-dose BPA furnishings in animals, including prostate weight and cancer, mammary gland organization and cancer, protein consecration in the uterus, organization of sexually dimorphic circuits in the hypothalamus, onset of estrus cyclicity and before puberty, body weight, genital malformations and others (reviewed in [4]); over 40 of these are below the RfD for BPA of l   μg/kg/twenty-four hours. Many of these endpoints are in areas of current concern for man epidemiological trends.

Because of its wide availability in the environment, and its estrogenic action in specific responses in vitro and in vivo, adverse effects of BPA exposure on human health are possible [10], [xi], [12], [13]. It has been hypothesized that exposure during early on development to xenoestrogens such equally BPA may be the underlying cause of the increased incidence of infertility, genital tract abnormalities, and breast cancer observed in European and The states human populations over the last 50 years [xiv], [fifteen], [16].

Here, we have outlined a number of studies that address the levels of BPA in human tissues and fluids. We have as well reviewed the few epidemiological studies available that explore the relationship between biological markers of BPA exposure with homo health outcomes. Nosotros have provided data from several studies that examine the levels of BPA released from consumer products likewise as the levels measured in wastewater, drinking h2o, air and dust. Human exposures are about likely through the oral route, although transdermal exposure by bathing in BPA-contaminated water is too a possible route, equally is exposure via inhalation; both of these latter routes of exposure would not be subjected to the extensive offset-laissez passer conjugation that occurs with oral ingestion. And finally, we have included several acute metabolic studies that have been performed, along with information available about BPA metabolism in fauna models. While this review is by no means comprehensive, we have covered most of the studies that are oft referenced in the extensive BPA literature.

Section snippets

BPA levels in human tissues and fluids

BPA levels have been measured in human fluids and tissues in many developed countries of the world. A full general consensus has been accepted that BPA tin can be detected in the bulk of individuals in these countries. The levels of BPA in residents of less-developed countries, still, remain unknown.

Epidemiology studies of human exposures

At this time, only a few epidemiological studies have been conducted to investigate the relationship between health-related endpoints and BPA exposure (Table iii). Several human studies have focused on identifying sources or levels of BPA exposure. Information technology is clear that boosted epidemiological studies are needed to establish relationships between BPA exposure and health outcomes, especially considering the extensive literature that now exist for agin effects on animals following exposure to depression

Levels of BPA in the surroundings

Near studies have focused on the potential for BPA exposure from dietary sources. In fact, a significant number of studies have been dedicated to determining BPA levels in foods, especially foods stored in cans with epoxy resin linings. A few other potential sources of BPA exposure, namely drinking water, air and dust, have received far less attention. While several studies have examined BPA leaching from landfills, additional studies are needed to examine these other potential sources and

BPA metabolism in humans and animals

The metabolic emptying pathways for BPA demand to be considered for man risk assessment. Nevertheless, just a limited number of human studies have addressed these issues for several reasons, including ethical considerations and difficulties in identifying individuals that are completely unexposed to BPA from the environs [33], [72]. In contrast, many studies take been dedicated to addressing the question of BPA metabolism in animal models, particularly rodents (Table 6). Yet, a major

Summary

Dozens of studies have been dedicated to monitoring levels of BPA in human tissues, blood, urine, and other fluids; extensive evidence exists to demonstrate that most humans are exposed to BPA. Unconjugated BPA has been measured repeatedly in man blood (serum and plasma), chest milk, amniotic fluid, and placental tissue in the low ng/ml or ng/thou range using diverse analytical techniques. Additionally, BPA conjugates have been repeatedly found in the low ng/ml range in the urine of over 90% of

BPA levels in human tissues and fluid

Human studies have shown that most children, as well equally adult men and women, including significant women, have measurable levels of BPA in body fluids and tissues sampled. Unconjugated BPA has been measured repeatedly in homo blood (serum and plasma) with a central measure out of the distribution in the 0.3–4.4   ng/ml range (1–19.4   nM), and in chest milk, amniotic fluid, and placental tissue in the depression ng/ml or ng/1000 range. The measurements of BPA in maternal serum, fetal serum, umbilical cord blood,

Acknowledgements

The authors gratefully acknowledge expertise and input from additional panel members: Jane C. Atkinson, Antonia M. Calafat, Frederick Eichmiller, Albert Kingman, Ruthann Rudel, and Kristina A. Thayer. This review was prepared in conjunction with the Bisphenol A Conference, Chapel Colina, NC, November 28–29, 2006. Back up was provided by the National Institute of Environmental Health Sciences and the National Institute of Dental and Craniofacial Inquiry, NIH, DHHS, the West.M. Keck Eye for

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