The draft CLARITY-BPA Core Study Research Report was reviewed by an external expert panel in April 2018. The final Core Study Research Report is expected in September 2018. A report integrating findings from the Core Study and Grantee Studies is expected in 2019.
Substances: Bisphenol A
Bisphenol A (BPA) is a chemical produced in large quantities for use primarily in the production of polycarbonate plastics, e.g., water and infant bottles, and epoxy resins which coat some metal food cans, bottle tops, and water supply pipes. According to data from the 2003-2004 National Health and Nutrition Examination Survey, 93% of Americans six years and older had detectable levels of BPA in their urine.
The Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA) program was developed to study the full range of potential health effects from exposure to BPA. The program was initiated by NIEHS, NTP, and the U.S. Food and Drug Administration (FDA) to provide data that can be used for regulatory decisions.
CLARITY-BPA has two components:
- Core Study: A two-year guideline-compliant study of potential BPA toxicity in rats, which was conducted according to federal regulatory and statutory guidelines for toxicity testing.
- Grantee Studies: Studies conducted by university researchers but testing a range of additional endpoints. The Grantee Studies used animals raised in the same conditions and exposed to the same doses of BPA as the Core Study.
These two components combined to produce a robust study design that unites standard research practices used by regulators with innovative studies conducted at universities.
One key strength is identical BPA exposure conditions for both components of the study, which were generated by the same facility in the FDA's National Center for Toxicological Research (NCTR). A second strength is that grantees received blinded Core Study samples, meaning they did not know whether samples had been dosed with BPA or how much, to minimize the potential for bias.
A report integrating findings from the Core Study and Grantee Studies is expected from NTP in 2019, as shown in the timeline.
The CLARITY-BPA program was overseen by a steering committee with members from NTP, NIEHS, NCTR, and researchers from the grantee institutions. In addition, an external scientific panel of three scientists provided overall programmatic guidance and offered advice in the management and technical performance of the research.
CLARITY-BPA Program: Core Study
The final CLARITY-BPA Core Study Research Report is scheduled for public release in September 2018.
The Core Study is one of two key components of CLARITY-BPA, along with the Grantee Studies. The draft CLARITY-BPA Core Study Research Report was reviewed by an external expert panel in April 2018.
The Core Study, which began in 2012, used rigorous laboratory methods to test potential BPA toxicity in rodents. It also provided animals and tissues with controlled BPA doses for further study by CLARITY-BPA grantees. The Core Study was conducted at the U.S. Food and Drug Administration's National Center for Toxicological Research (NCTR) according to guideline-compliant research standards, meaning the protocols follow federal regulatory and statutory guidelines for toxicity testing.
The strain and numbers of animals, animal diet, housing conditions, BPA doses, and route of exposure to BPA were tightly controlled. To protect the integrity of the data, CLARITY-BPA grantees were blinded to the BPA exposure levels of the animals and tissues that they received for further study.
- Pregnant Sprague-Dawley rats were orally dosed with one of three substances:
- BPA – 2.5, 25, 250, 2500, or 25000 micrograms per kilogram of body weight per day, to cover the wide range of BPA doses with reported effects in the scientific literature.
- Vehicle Control – the harmless solution used for administering BPA.
- Estrogen Control – 0.05 or 0.5 micrograms per kilogram of body weight per day of ethinyl estradiol, so the animals' response to a classic estrogen could be compared with response to BPA.
- The offspring were orally dosed with the same substance and dose, either daily throughout the two-year study (Continuous Dose) or daily until weaned (Stop Dose).
- For the estrogen control, the offspring were also orally dosed daily throughout the two-year study.
- NCTR staff oversaw the Core Study and collected and sent blinded tissue samples or study animals to CLARITY-BPA grantees.
- Study endpoints were examined at three timeframes: ongoing (throughout the two-year study); interim (1 year); and terminal (2 years).
CLARITY-BPA Program: Grantee Studies
Grantee data are scheduled for public release in September 2018.
The Grantee Studies are one of two key components of CLARITY-BPA, along with the Core Study. These studies used animals raised in the same conditions and exposed to the same doses of BPA as the Core Study, and the researchers were blinded to the doses of BPA that the animals or tissues received. These studies were conducted through 13 grants awarded to 14 researchers (RFA-ES-10-009).
The table below lists each grantee, their institution, their study focus area, and links to their published results.
|Principal Investigator||Institution||Study Focus Area||Publications|
|Scott Belcher||North Carolina State University||Heart|
|Nira Ben-Jonathan||University of Cincinnati||Obesity/Adipose Tissue|
|Kim Boekelheide||Brown University||Testis/Sperm|
|Jodi Flaws||University of Illinois at Urbana-Champaign||Ovary|
|Nestor Gonzalez-Cadavid||University of California, Los Angeles||Penis|
|Andrew Greenberg||Tufts University||Diabetes/Pancreas/Liver|
|Shuk-Mei Ho||University of Cincinnati||Uterus|
|Norbert Kaminski||Michigan State University||Immune/Spleen/Thymus|
|Heather Patisaul||North Carolina State University||Behavior/Brain|
|Gail Prins||University of Illinois at Chicago||Prostate|
|Cheryl Rosenfeld||University of Missouri||Behavior/Brain|
|Ana Soto||Tufts University||Mammary Gland|
|Frederick vom Saal||University of Missouri||Urogenital System|
|Thomas Zoeller||University of Massachusetts Amherst||Thyroid/Brain|
- Bisphenol A
Updated August 2010
- Expert Panel Reviews CLARITY-BPA Core Study
Environmental Factor, May 2018
- BPA Grantees Share Findings
Environmental Factor, March 2013
- Researchers Offer Recommendations for BPA Study Design
Environmental Factor, April 2013
- NIEHS Grantees Collaborate with NTP, FDA on BPA studies
Environmental Factor, November 2011
- Camacho L, Basavarajappa MS, Chang C-W, Han T, Kobets T, Koturbash I, Surratt G, Lewis SM, Vanlandingham MM, Fuscoe JC, Gamboa da Costa G, Pogribny IP, Delclos KB. 2015. Effect of oral exposure to bisphenol A on gene expression and global genomic DNA methylation in the prostate, female mammary gland, and uterus of NCTR Sprague-Dawley rats. Food Chem Toxicol 81:92–103; http://dx.doi.org/10.1016/j.fct.2015.04.009
- Churchwell MI, Camacho L, Vanlandingham MM, Twaddle NC, Sepehr E, Delclos KB, Fisher JW, Doerge DR. 2014. Comparison of life-stage-dependent internal dosimetry for bisphenol A, ethinyl estradiol, a reference estrogen, and endogenous estradiol to test an estrogenic mode of action in Sprague Dawley rats. Toxicol Sci 139:4–20; http://doi.org/10.1093/toxsci/kfu021
- Delclos KB, Camacho L, Lewis SM, Vanlandingham MM, Latendresse JR, Olson GR, Davis KJ, Patton RE, Gamboa da Costa G, Woodling KA, Bryant MS, Chidambaram M, Trbojevich R, Juliar BE, Felton RP, Thorn BT. 2014. Toxicity evaluation of bisphenol A administered by gavage to Sprague Dawley rats from gestation day 6 through postnatal day 90. Toxicol Sci 139:174–197; http://doi.org/10.1093/toxsci/kfu022
- Heindel JJ, Newbold RR, Bucher JR, Camacho L, Delclos KB, Lewis SM, Vanlandingham M, Churchwell MI, Twaddle NC, McLellen M, Chidambaram M, Bryant M, Woodling K, Gamboa da Costa G, Ferguson SA, Flaws J, Howard PC, Walker NJ, Zoeller RT, Fostel J, Favaro C, Schug TT. 2015. NIEHS/FDA CLARITY-BPA research program update. Reprod Toxicol 58:33–44; http://dx.doi.org/10.1016/j.reprotox.2015.07.075
- Rebuli ME, Cao J, Sluzas E, Delclos KB, Camacho L, Lewis SM, Vanlandingham MM, Patisaul HB. 2014. Investigation of the effects of subchronic low dose oral exposure to bisphenol A (BPA) and ethinyl estradiol (EE) on estrogen receptor expression in the juvenile and adult female rat hypothalamus. Toxicol Sci 140:190–203; http://dx.doi.org/10.1093/toxsci/kfu074
- Schug TT, Heindel JJ, Camacho L, Delclos KB, Howard P, Johnson AF, Aungst J, Keefe D, Newbold R, Walker NJ, Zoeller RT, Bucher JR. 2013. A new approach to synergize academic and guideline-compliant research: The CLARITY-BPA research program. Reprod Toxicol 40:35–40; http://doi.org/10.1016/j.reprotox.2013.05.010
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