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Ultra Sensitive Analysis Of Polycyclic Aromatic Hydrocarbon Dibenzo[def,p]chrysene
Pharmacokinetics In Humans
Superfund Annual Meeting 2014
Erin Madeen
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PAH Exposure: in mixtures
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Why DBC? Why humans? • Reductionist: study individual PAHs to build data
for mixture meta-analysis predictions
• Unusual Conformation :“fjord” and bay regions,
unusual conformation
• No Data: PK/PD data not available from human
exposure
• Model: Validate computational Physiologically
Based Pharmacokinetic Model predictions
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Hypothesis:
The in vivo human pharmacodynamics of DBC, as detected by AMS, can be incorporated into a model for predicting environmentally relevant human metabolism.
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Study Design
Sample
Generation
Sample Prep
Data and
analysis
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1MV Bio-AMS
T.J. Ognibene , G.A. Salazar
Installation of hybrid ion source on the 1-MV LLNL BioAMS spectrometer
Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms Volume 294 2013
311 - 314
Gas (CO2)
ionization
source
Accelerator
14C
detector
12C
detector
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Moving Wire Video
• https://www.youtube.com/watch?v=oFi17Vho44k
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315nm HPLC chromatogram
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N HPLC PDA@315 (A.U.)
N HPLC PDA@315 (A.U.)
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N HPLC PDA@315 (A.U.)
N 12C (uCoul)
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N HPLC PDA@315 (A.U.)
N 14C (counts)
N 12C (uCoul)
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0.75h Plasma 14C compared to DBC standards
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lve
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Conclusion
• Hypothesis: Supported
– Human environmentally relevant pharmacodynamics of DBC.
• Fast uptake (Tmax 0.75 h)
• Rapid alpha elimination of majority, followed by delayed beta elimination
• Unmetabolized parent constitutes the majority of 14C signal in plasma extract
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Collaboration
PNNL
OSU SRP
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Thank You
Bill Baird
Dave Williams
Sharon Krueger
Beth Siddens
Tammie McQuistan
Ken Turteltaub
Ted Ognibene
Graham Bench
Mike Malfatti
Kurt Haack
Rick Corley
Susie Crowell
Funding:OSU:P42-ES016465, P42-ES019465-S2, T32-ES000760; LLNL:P41-RR013461
Tod Harper
Hannah You
David Sampson
Williams/Baird Lab Group