Critical evaluation of key evidence on the human health hazards of exposure to bisphenol A

Abstract

Despite the fact that more than 5000 safety-related studies have been published on bisphenol A (BPA), there seems to be no resolution of the apparently deadlocked controversy as to whether exposure of the general population to BPA causes adverse effects due to its estrogenicity. Therefore, the Advisory Committee of the German Society of Toxicology reviewed the background and cutting-edge topics of this BPA controversy. The current tolerable daily intake value (TDI) of 0.05 mg/kg body weight [bw]/day, derived by the European Food Safety Authority (EFSA), is mainly based on body weight changes in two- and three-generation studies in mice and rats. Recently, these studies and the derivation of the TDI have been criticized. After having carefully considered all arguments, the Committee had to conclude that the criticism was scientifically not justified; moreover, recently published additional data further support the reliability of the two-and three-generation studies demonstrating a lack of estrogen-dependent effects at and below doses on which the current TDI is based. A frequently discussed topic is whether doses below 5 mg/ kg bw/day may cause adverse health effects in laboratory animals. Meanwhile, it has become clear that positive results from some explorative studies have not been confirmed in subsequent studies with higher numbers of animals or a priori defined hypotheses. Particularly relevant are some recent studies with negative outcomes that addressed effects of BPA on the brain, behavior, and the prostate in rodents for extrapolation to the human situation. The Committee came to the conclusion that rodent data can well be used as a basis for human risk evaluation. Currently published conjectures that rats are insensitive to estrogens compared to humans can be refuted. Data from toxicokinetics studies show that the half-life of BPA in adult human subjects is less than 2 hours and BPA is completely recovered in urine as BPA-conjugates. Tissue deconjugation of BPA-glucuronide and -sulfate may occur. Because of the extremely low quantities, it is only of minor relevance for BPA toxicity. Biomonitoring studies have been used to estimate human BPA exposure and show that the daily intake of BPA is far below the TDI for the general population. Further topics addressed in this article include reasons why some studies on BPA are not reproducible; the relevance of oral versus non-oral exposure routes; the degree to which newborns are at higher systemic BPA exposure; increased BPA exposure by infusions in intensive care units; mechanisms of action other than estrogen receptor activation; and the current regulatory status in Europe, as well as in the USA, Canada, Japan, New Zealand, and Australia. Overall, the Committee concluded that the current TDI for BPA is adequately justified and that the available evidence indicates that BPA exposure represents no noteworthy risk to the health of the human population, including newborns and babies.

The role of environmental estrogens and autoimmunity

“…A recently published paper reviewed more than 5000 safety-related studies, concluding that exposure to bisphenol-A represents no noteworthy risk to the health of the human population [29]. However, in vitro data suggested that bisphenol-A could display some effects on the immune system: it has been shown to inhibit the synthesis of monocyte-chemoattractant protein (MCP) -1 in a tumor cell line, with a potency three times greater than that of E2 [30].…”

Gestational and lactational exposure to low-dose bisphenol A increases Th17 cells in mice offspring

“…BPA is readily released from these products into food and water, and hence contributes to human exposure through diet or drinking water (Hengstler et al, 2011;Michałowicz, 2014). Bio-monitoring studies have reported that BPA can be detected in over 90% of blood, urine and other tissue samples around the world (Vandenberg et al, 2010).…”

BPA Free Waters Essential to Perform Laboratory Studies

“…The resultant LOD and LOQ were 0.0012 and 0.004 ng/mL, respectively. Standard and spiked samples at three different BPA concentration (1, 10, 100 ng/mL) were extracted range of 0.05-3.0 ng/mL [1][2][3][4][5][6][7]. Our data has shown that similar level of BPA is into purified water.…”

“…Analyses were performed in the multiple reaction monitoring (MRM) mode and negative ionization. The product ions at 133.2 m/z and 212.1 m/z for BPA and at 138.2 m/z and 215.0 m/z for d 6 -BPA (IS) were monitored to assess unambiguous identification. The linearity of the detector response was verified over the concentration range 0.100-200 ng/mL.…”

“…It has been suggested that this exposure to low doses of BPA may be associated with increased susceptibility to reproductive and neurobehavioral disorders, heart disease, type 2 diabetes, prostate and breast cancer, and many other diseases [1][2][3][4][5]. These potential adverse health effects have been also assessed by several studies performed in rodent models for the purpose of extrapolating data to humans [6,7].…”