Assessment of recent developmental immunotoxicity studies with bisphenol A in the context of the 2015 EFSA t-TDI

Abstract

Summary Humans are exposed to bisphenol A (BPA) mainly through the diet, air, dust, skin contact and water. There are concerns about adverse health effects in humans due to exposure to bisphenol A (BPA). The European Food Safety Authority (EFSA) has extensively reviewed the available literature to establish a temporary Tolerable Daily Intake (t-TDI). This exposure level was based on all available literature published before the end of 2012. Since then, new experimental animal studies have emerged, including those that identified effects of BPA on the immune system after developmental exposure. These studies indicate that developmental immunotoxicity might occur at lower dose levels than previously observed and on which the current EFSA t-TDI is based. The Dutch National Institute for Public Health and the Environment (RIVM) organized an expert workshop in September 2015 to consider recently published studies on the developmental immunotoxicity of bisphenol A (BPA). Key studies were discussed in the context of other experimental studies. The workshop concluded that these new experimental studies provide credible evidence for adverse immune effects after developmental exposure to BPA at 5 μg/kg BW/day from gestation day 15 to postnatal day 21. Supportive evidence for adverse immune effects in similar dose ranges was obtained from other publications that were discussed during the workshop. The dose level associated with adverse immune effects is considerably lower than the dose used by EFSA for deriving the t-TDI. The workshop unanimously concluded that the current EFSA t-TDI warrants reconsideration in the context of all currently available data.

CLARITY‐BPA academic laboratory studies identify consistent low‐dose Bisphenol A effects on multiple organ systems

“…Effects of BPA on innate immune responses were also observed . Prior to CLARITY, an expert panel concluded that there was credible evidence that BPA could induce abnormal immune responses after relatively low levels of exposure (5 μg/kg BW/d) during development …”

“…117 Prior to CLARITY, an expert panel concluded that there was credible evidence that BPA could induce abnormal immune responses after relatively low levels of exposure (5 μg/kg BW/d) during development. 118 Within the CLARITY-BPA consortium, the Kaminski laboratory examined immune cell populations residing in the spleen and thymus. 119 Only animals that were continuously exposed to BPA throughout life were utilized in two published studies resulting from this work.…”

Impacts of Bisphenol A and Ethinyl Estradiol on Male and Female CD-1 Mouse Spleen

“…Along with concerns related to the effects of estrogenic EDCs like BPA on the reproductive system, there is much scientific and public health interest related to answering the question of whether or not BPA influences the function of the immune system 8, 9 . The idea that environmental estrogens alter immune function is founded upon important differences in the inflammatory responses of females and males.…”

Impacts of Bisphenol A and Ethinyl Estradiol on Male and Female CD-1 Mouse Spleen

“…The foundations of the presented studies were based on our previous observations that the estrogenic actions of BPA and EE could induce pathologic fibrosis and inflammatory pathology of the uterus of exposed females 23,24 . Other previous studies have investigated the potential for the endocrine disruptor BPA to disrupt immune function by focusing on determining whether BPA exposure altered various physiologic properties of isolated immune cells, by establishing an association between exposure and inflammatory or autoimmune disease, or whether exposure to BPA modified immune or inflammatory responses in specific animal models 9,10,30 .…”

“…The disruptive mechanisms of BPA action are related to estrogen signaling, which in some cases can also result in alterations of thyroid hormone and androgen signaling, and abnormal hormonal control of metabolism [6][7][8] . Along with concerns related to estrogenic EDCs like BPA having direct effects on the reproductive system, there is much scientific and public health interest related to answering the question of whether or not BPA influences the function of the immune system 9,10 . The idea that environmental estrogens alter immune function is founded upon important differences in the inflammatory responses of females and males.…”