CLARITY-BPA: Effects of chronic Bisphenol A exposure on the immune system: Part 1 - Quantification of the relative number and proportion of leukocyte populations in the spleen and thymus

Toxicology. 2018 Mar 1;396-397:46-53. doi: 10.1016/j.tox.2018.01.004. Epub 2018 Feb 8.


Bisphenol A (BPA) is extensively used in manufacturing of a broad range of consumer products worldwide. Due to its widespread use, human exposure to BPA is virtually ubiquitous. Broad human exposure coupled with a large scientific literature describing estrogenic activity of BPA in animals has raised public health concerns. To comprehensively evaluate the health effects of BPA exposure, a chronic toxicity study using a wide-range of BPA doses (2.5-25000 μg/kg bw/day) was conducted jointly by the NTP, thirteen NIEHS-supported grantees, and the FDA, which is called the Consortium Linking Academic and Regulatory Insights on Toxicity of BPA (CLARITY-BPA). As a participant in the CLARITY-BPA project, the objective of the current study was to evaluate the effects of chronic BPA exposure in Sprague-Dawley rats on the relative number and proportion of defined leukocyte populations in the spleen and the thymus. Toward this end, lymphoid tissues from a total of 641 rats were assayed after being continuously dosed with BPA or controls for up to one year. To comprehensively evaluate the effects of BPA on leukocyte compositions, extensive endpoints that cover major populations of leukocytes were assessed, including B cells, T cells, NK cells, granulocytes, monocytes, macrophages and dendritic cells. In total, of the 530 measurements in BPA-treated rats, 10 measurements were statistically different from vehicle controls and were mainly associated with either the macrophage or dendritic cell populations. Most, if not all, of these alterations were found to be transient with no persistent trend over the one-year time period. In addition, the observed BPA-associated alterations were mostly moderate in magnitude and not dose-dependent. Due to the aforementioned, it is unlikely that the observed BPA-mediated changes alone would adversely affect immune competence.

Keywords: BPA; Bisphenol A; CLARITY-BPA; Immune system; Immunotoxicity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Benzhydryl Compounds / toxicity*
  • Dose-Response Relationship, Drug
  • Endocrine Disruptors / toxicity*
  • Female
  • Immune System / drug effects*
  • Leukocyte Count
  • Leukocytes / drug effects*
  • Male
  • Phenols / toxicity*
  • Rats
  • Rats, Sprague-Dawley
  • Sex Characteristics
  • Spleen / cytology*
  • Spleen / drug effects*
  • Thymocytes / drug effects
  • Thymus Gland / cytology*
  • Thymus Gland / drug effects*
  • Thymus Gland / growth & development


  • Benzhydryl Compounds
  • Endocrine Disruptors
  • Phenols
  • bisphenol A