ARRA IMPACT REPORT:
Bisphenol A (BPA)


Public Health Burden
Bisphenol A (BPA) is a chemical produced in large quantities in the coating of food cans, bottle tops, and water supply pipes, as well as the manufacturing of plastics for mobile phone housings, household items, and automobiles.  Because BPA migrates from food and beverage containers into the things we consume, the most frequent human exposure to BPA is from diet. Detailed studies need to be done on BPA, including dose responses, low-dose effects, non-monotonic dose responses, pharmacokinetics across species and the lifespan, gender differences, human exposure and routes of exposure, sensitive windows of exposure, mechanism(s), and specific disease endpoints.

ARRA BPA Research Support and Goals
The National Institute of Environmental Health Sciences invested a substantial amount of ARRA funds in BPA research to define its effects on human health. The ARRA “signature projects” were carried out within a broader context of ongoing endocrine disruptor (ED) and BPA research.

The ARRA projects themselves were distinct from other projects in the portfolios in that they:

  • operated as a research consortium, meaning that grantees worked together throughout the life of the grant with federal partners to coordinate research in response to specific regulatory information needs;
  • had discrete goals that could be addressed within the two-year ARRA investment period.
The primary goal of the ARRA Grand Opportunities (GO) program as stated in the RFA was to: “produce both the animal and human data to allow for a comprehensive assessment of the human health effects of BPA.”Specifically, the program aimed to address gaps in evidence linking BPA exposure to human health effects and the related ability to help inform the regulatory process at the Food and Drug Administration (FDA). The ARRA GO grantees incorporated specific methods in their research designs, such as oral dosing, studies with males and females, a broader dose range, and overlapping endpoints among animal studies and between animal and human studies.

Standardizing protocols for analyzing effects of BPA exposure in animals and humans
In order to ensure that all grantees were following identical protocols, the researchers collaborated to design a standard research protocol that analyzed a range of low dose exposure measures and used both multiple doses and low doses. The researchers also tested several methods for measuring BPA in blood and in urine in both animals and humans and selected those methods that were most reliable. Researchers utilized these standard protocols and measurement methods in order to build a body of research that has been replicated and validated in multiple research facilities across the country. Finally, the grantees applied methods from one study to other organ systems, populations, or human/animal species, using the human studies to validate what was being found in the animal studies.

Documenting the health effects of BPA exposure
In order to fully understand the risk that BPA poses for human health, researchers identified the health effects of BPA exposure. Researchers found that BPA exposure can affect brain, behavior, and learning, and these outcomes may vary by gender.1 Using ARRA funding, researchers also found that low doses of BPA have sex-specific effects on heart cells and can cause rapid arrhythmogenic events in female via changes in ERa and ERß signaling.2 In ARRA-funded studies using rhesus monkeys, BPA was reported to affect ovarian and mammary gland development.3

Documenting development effects of BPA exposure
With ARRA funds, researchers also examined the possible impact that early life exposure to BPA has on development. Grantees found that early life exposure to BPA in rats alters DNA methylation and gene expression in the prostate gland throughout life4 . They also found that in mice, early life exposure to environmentally relevant levels of BPA decreases fertility and fecundity5. Finally, grantees found that BPA concentration in the blood may influence embryo quality indicators during in vitro fertilization.5

Beyond ARRA

The Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA) research program is a collaborative effort between NIEHS and FDA to conduct a perinatal 2-year chronic toxicity study on BPA. In addition to the core elements of a guideline-compliant study, the 2-year study involves extramural research partners and will incorporate a wide range of doses and disease-relevant endpoints. The 2-year study is expected to begin in September 2012 and conclude in early 2015.

Contributing NIH Institutes & Centers

  • National Institute of Environmental Health Sciences (NIEHS)

  1. 1RC1ES018195-01, http://www.ncbi.nlm.nih.gov/pubmed/3136312 - ROSENFELD, CHERYL SUSAN - UNIVERSITY OF MISSOURI-COLUMBIA - COLUMBIA - MO
  2. 1RC2ES018765-01, http://www.ncbi.nlm.nih.gov/pubmed/3275382 - BELCHER, SCOTT M - UNIVERSITY OF CINCINNATI - CINCINNATI - OH
  3. 1RC2ES018822-01, http://www.ncbi.nlm.nih.gov/pubmed/22566636, http://www.ncbi.nlm.nih.gov/pubmed/23012422 - SOTO, ANA - TUFTS UNIVERSITY BOSTON - BOSTON - MA
  4. 1RC2ES018758-01 - PRINS, GAIL S - UNIVERSITY OF ILLINOIS - CHICAGO - IL
    1RC2ES018789-01 - WALKER, CHERYL L. - UNIVERSITY OF TEXAS MD ANDERSON CAN CTR - HOUSTON - TX
    http://www.ncbi.nlm.nih.gov/pubmed/3249669
  5. 1RC2ES018764-01, http://www.ncbi.nlm.nih.gov/pubmed/3157013 - VOM SAAL, FREDERICK S - UNIVERSITY OF MISSOURI-COLUMBIA - COLUMBIA - MO