Final Report: Assessing Maternal and Fetal Exposure to ChemicalsEPA Grant Number: R834678C001
Subproject: this is subproject number 001 , established and managed by the Center Director under grant R834678
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Children's Environmental Health and Disease Prevention Research Center: Formative Center - University of California, San Francisco
Center Director: Woodruff, Tracey J.
Title: Assessing Maternal and Fetal Exposure to Chemicals
Investigators: Woodruff, Tracey J. , Stotland, Naomi , Gerona, Roy
Institution: University of California - San Francisco
EPA Project Officer: Hahn, Intaek
Project Period: May 1, 2010 through April 30, 2013
RFA: Children's Environmental Health and Disease Prevention Research Centers: Formative Centers (with NIEHS) (2009) RFA Text | Recipients Lists
Research Category: Children's Health , Health
To generate unprecedented data on chemical exposures during the second trimester of pregnancy, when certain aspects of fetal development are particularly vulnerable to disruption. The specific aims of the project are to: (1) compare maternal and fetal exposures to BPA during the second trimester, and (2) to explore the feasibility and accuracy of using maternal biological biomonitoring results to predict fetal exposures.
We successfully recruited 181 women from September 2010 to April 2012 (target 100). We collected 125 urines and 111 urines on the first and second day visits of the participants (procedure second day). We collected 82 umbilical cord bloods, 162 placentas and 153 livers from the procedure.
Our collaborator, Dr. Roy Gerona, has developed an improved method for analyzing unconjugated BPA, BPA sulfate and BPA glucuronide, has measured all of these in our umbilical cord serum and urine samples and has completed the method development and preliminary analysis for a subset of the liver tissues (N = 20) and amniotic fluid samples (N = 7). Additionally, during the method development phase, Dr. Gerona discovered a source of BPA contamination in our maternal serum samples from the BD Vacutainer Push Button Blood Collection Set used in the hospital. He also determined there was no contamination from using straight needles. However, given the difficulty of using a straight needle versus a butterfly for the phlebotomists in the clinic, we were only able to collect 20 percent of our serum samples this way. We also tested eight different models of butterfly vacutainers and have found 2 BPA-free replacements, and we implemented use of one (BD Vacutainer Eclipse 21G needle) starting on November 29, 2011. Results from the BPA contamination investigation have been submitted as a communication article to Chemosphere. Finally, as a supplement to this project, we led and participated in a round robin for measuring unconjugated BPA in human blood with a goal of identifying whether unconjugated BPA could be measured accurately in human blood.
Results: Among our study participants, 100 percent had detectable BPA levels in non-fasting urine. Levels of total BPA, BPA glucuronide, BPA sulfate, and unconjugated BPA are up to three times higher compared to other studies measuring BPA in pregnant women in the United States and other countries worldwide, possibly due to underlying demographic and behavioral characteristics of our unique study population (lower income, 40% smokers, racially diverse population). BPA analytic methods also may contribute, as we use an LC-MS/MS technique to directly measure unconjugated BPA and BPA conjugates without enzyme hydrolysis used in previous studies. Enzyme hydrolysis could induce sample loss.
For the first time, we measured unconjugated and conjugated BPA in umbilical cord serum. We found a geometric mean for BPA glucuronide of 0.14 ng/mL, and 0.32 ng/mL for BPA sulfate. Unconjugated BPA was detected in 47 percent of umbilical cord serum samples, and 29 percent of samples had more unconjugated BPA than conjugated. Although unconjugated BPA was not universally detected, maximum concentrations of unconjugated BPA measured (52.3 ng/mL) are the highest reported to date. In a subset of matched umbilical cord serum and maternal urine samples (n = 29), we found higher levels of total BPA in umbilical cord serum in approximately 20 percent of samples, and higher levels of unconjugated BPA in umbilical cord serum in 45 percent of samples. We also observed positive correlations in unconjugated and conjugated BPA levels between urine and cord blood. Further, we have shown, for the first time in humans, the importance of the sulfonation metabolic pathway as an alternative to glucoronidation, likely due to immaturity of the UGT enzymes. Results on BPA analysis methods and umbilical cord serum BPA levels have been published in Environmental Science and Technology (PMID: 23941471).
In our analysis of the first 10 fetal liver samples we have found that the major form of BPA is free or unconjugated BPA, which is present in 100 percent of the samples. In addition, we have found that BPA sulfate is slightly higher in these samples than BPA glucuronide and are the first to report the two conjugates differentiated. We are currently in the process of analyzing the remaining liver samples for BPA. We have developed a method for BPA analysis in amniotic fluid and will be using it to analyze samples in our new PEEC Children’s Center Grant.
For the Round Robin, four labs participated (including our own). We identified collection materials and reagents that did not introduce BPA contamination. In the blinded spiked sample analysis, all labs were able to distinguish low from high values of unconjugated BPA and BPA glucuronide. By completion of the Round Robin, three labs had verified methods for the analysis of unconjugated BPA and two verified for the analysis of BPA glucuronide (determined by: 4 of 5 samples within 20 percent of spiked concentrations). In the analysis of BPA glucuronide only spiked samples, all laboratories reported BPA glucuronide was the majority of BPA detected (92.2 – 100%). Finally, labs were more likely to be verified using direct methods than indirect ones using enzymatic hydrolysis. A submitted paper is under review at Environmental Health.
Journal Articles on this Report : 2 Displayed | Download in RIS Format
|Other subproject views:||All 2 publications||2 publications in selected types||All 2 journal articles|
|Other center views:||All 79 publications||20 publications in selected types||All 16 journal articles|
||Gerona RR, Woodruff TJ, Dickenson CA, Pan J, Schwartz JM, Sen S, Friesen MW, Fujimoto VY, Hunt PA. Bisphenol-A (BPA), BPA glucuronide, and BPA sulfate in midgestation umbilical cord serum in a northern and central California population. Environmental Science & Technology 2013;47(21):12477-12485.||
||Vandenberg LN, Gerona RR, Kannan K, Taylor JA, van Breemen RB, Dickenson CA, Liao C, Yuan Y, Newbold RR, Padmanabhan V, vom Saal FS, Woodruff TJ. A round robin approach to the analysis of bisphenol A (BPA) in human blood samples. Environmental Health 2014;13(1):25 (20 pp.).||
Supplemental Keywords:Risk assessment, metabolism, bioavailability, ethnic groups, endocrine disruptors, sensitive populations, decision making, measurement methods, RFA, Health, Scientific Discipline, INTERNATIONAL COOPERATION, Biochemistry, Children's Health, Environmental Policy, Biology, prenatal exposure, biological response, chemical mixtures, children's vulnerablity, assessment of exposure, children's environmental health
Progress and Final Reports:Original Abstract
Main Center Abstract and Reports:R834678 Children's Environmental Health and Disease Prevention Research Center: Formative Center - University of California, San Francisco
Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R834678C001 Assessing Maternal and Fetal Exposure to Chemicals
R834678C002 Assessing the Effects of BPA Exposure on Early Human Development
R834678C003 (Pilot Study): Predictors of Maternal Exposure to BPA During Pregnancy