Grantee Research Project Results
2010 Progress Report: Urinary Biomarker Kinetics to Quantify Human Bisphenol A Exposure and Endocrine System Target Tissue Dosimetry
EPA Grant Number: R833868Title: Urinary Biomarker Kinetics to Quantify Human Bisphenol A Exposure and Endocrine System Target Tissue Dosimetry
Investigators: Teeguarden, Justin , Hattis, Dale , Hinderliter, Paul
Institution: Battelle Memorial Institute , Clark University
EPA Project Officer: Hahn, Intaek
Project Period: July 1, 2009 through June 30, 2012
Project Period Covered by this Report: July 1, 2009 through June 30,2010
Project Amount: $749,967
RFA: Interpretation of Biomarkers Using Physiologically Based Pharmacokinetic Modeling (2007) RFA Text | Recipients Lists
Research Category: Human Health
Objective:
During the last part of 2009, we completed IRB approvals, protocols and planning for the BPA clinical exposure assessment study. The study was completed over the next 6 months. This study was essential to progress because it addressed major issues. First, it allowed us to evaluate how similar pharmacokinetics of BPA were in humans exposed by capsule and diet, enabling improvement of the reverse dosimetry model for BPA. From a safety perspective, the most pressing fundamental question regarding BPA is whether human blood/tissue concentrations of BPA following typical daily exposures are similar to, above, or below blood/tissue concentrations causing demonstrably adverse effects in animal models. The other objective of this study was to characterize internal exposure to TOTBPA and BPA by concurrently determining the 24-h urinary elimination profile of TOTBPA and the serum time course of TOTBPA and BPA in a group of healthy adult humans on a controlled diet enriched in canned food items likely to be significant dietary sources of BPA. In addition, we sought to produce an accurate measure of human exposure to BPA before and after consuming a potentially BPA-rich diet and characterize hourly fluctuations in serum and urine BPA.
Progress Summary:
Dr. Rudy Gunawan, Ph.D., in applied mathematics was hired as a postdoctoral fellow to lead the development and application of the reverse dosimetry PBPK model for BPA and to assist in analysis of the clinical exposure data. Dr. Gunawan left in response to an unusually good job offer before completing his fellowship.
A collaboration with the National Center for Toxicological Research (Dr. Daniel Doerge) was established to provide additional analytical support. The objective of this collaboration was to provide additional rigor and validation in the area of BPA analytical measurements in blood.
The clinical exposure study was highly successful and without incident. Twenty-four hour urine and serum concentrations were obtained from 20 volunteers, providing sufficient data to meet both objectives. The main conclusion of the study was that in humans externally exposed by the diet to a high (relative to the normal U.S. Population) bioactive form of the compound is present in levels that are below the limit of detection. External exposures were on average above the 95th percentile for U.S. adult exposure and in approximately one-half of the volunteers, 1.3-4 times higher than the 95th percentile.
Future Activities:
Over the next project period, we will continue to develop the reverse dosimetry model and apply it to the NHANES data, per the specific aims in the grant.
Journal Articles on this Report : 3 Displayed | Download in RIS Format
Other project views: | All 3 publications | 3 publications in selected types | All 3 journal articles |
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Teeguarden JG, Calafat AM, Ye X, Doerge DR, Churchwell MI, Gunawan R, Graham MK. Twenty-four hour human urine and serum profiles of Bisphenol A during high-dietary exposure. Toxicological Sciences 2011;123(1):48-57. |
R833868 (2010) |
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Teeguarden JG, Hanson-Drury S. A systematic review of Bisphenol A “low dose” studies in the context of human exposure: a case for establishing standards for reporting “low-dose” effects of chemicals. Food and Chemical Toxicology 2013;62:935-948. |
R833868 (2010) |
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Teeguarden J, Hanson-Drury S, Fisher JW, Doerge DR. Are typical human serum BPA concentrations measurable and sufficient to be estrogenic in the general population? Food and Chemical Toxicology 2013;62:949-963. |
R833868 (2010) |
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Progress and Final Reports:
Original AbstractThe perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.