CLARITY-BPA: Effects of chronic bisphenol A exposure on the immune system: Part 2 - Characterization of lymphoproliferative and immune effector responses by splenic leukocytes

Toxicology. 2018 Mar 1;396-397:54-67. doi: 10.1016/j.tox.2018.02.004. Epub 2018 Feb 7.


Bisphenol A (BPA) is commonly used in the manufacturing of a wide range of consumer products, including polycarbonate plastics, epoxy resin that lines beverage and food cans, and some dental sealants. Consumption of food and beverages containing BPA represents the primary route of human BPA exposure, which is virtually ubiquitous. An increasing number of studies have evaluated the effects of BPA on immune responses in laboratory animals that have reported a variety of effects some of which have been contradictory. To address the divergent findings surrounding BPA exposure, a comprehensive chronic treatment study of BPA was conducted in Sprague-Dawley rats, termed the Consortium Linking Academic and Regulatory Insights on Toxicity of BPA (CLARITY-BPA). As a participant in the CLARITY-BPA project, our studies evaluated the effects of BPA on a broad range of immune function endpoints using spleen cells isolated from BPA or vehicle treated rats. This comprehensive assessment included measurements of lymphoproliferation in response to mitogenic stimuli, immunoglobulin production by B cells, and cellular activation of T cells, NK cells, monocytes, granulocytes, macrophages and dendritic cells. In total, 630 different measurements in BPA treated rats were performed of which 35 measurements were statistically different from vehicle controls. The most substantive alteration associated with BPA treatment was the augmentation of lymphoproliferation in response to pokeweed mitogen stimulations in 1 year old male rats, which was also observed in the reference estrogen ethinyl estradiol treated groups. With the exception of the aforementioned, the statistically significant changes associated with BPA treatment were mostly sporadic and not dose-dependent with only one out of five BPA dose groups showing a statistical difference. In addition, the observed BPA-associated alterations were mostly moderate in magnitude and showed no persistent trend over the one-year time period. Based on these findings, we conclude that the observed BPA-mediated changes observed in this study are unlikely to alter immune competence in adult rats.

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

Publication types

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

MeSH terms

  • Animals
  • B-Lymphocytes / drug effects
  • Benzhydryl Compounds / toxicity*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Endocrine Disruptors / toxicity*
  • Immunoglobulin M / biosynthesis
  • Killer Cells, Natural / drug effects
  • Leukocyte Count
  • Leukocytes / drug effects*
  • Lymphocyte Count
  • Lymphocytes / drug effects*
  • Male
  • Myeloid Cells / drug effects
  • Phenols / toxicity*
  • Rats
  • Rats, Sprague-Dawley
  • Spleen / cytology*
  • Spleen / drug effects
  • T-Lymphocytes / drug effects


  • Benzhydryl Compounds
  • Endocrine Disruptors
  • Immunoglobulin M
  • Phenols
  • bisphenol A