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Ultra Sensitive Analysis Of Polycyclic Aromatic Hydrocarbon Dibenzo[def,p]chrysene
Pharmacokinetics In Humans
Superfund Annual Meeting 2014
Erin Madeen
PAH Exposure: in mixtures
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
Hypothesis:
The in vivo human pharmacodynamics of DBC, as detected by AMS, can be incorporated into a model for predicting environmentally relevant human metabolism.
Study Design
Sample
Generation
Sample Prep
Data and
analysis
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
Moving Wire Video
• https://www.youtube.com/watch?v=oFi17Vho44k
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)
0.75h Plasma 14C compared to DBC standards
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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
Collaboration
PNNL
OSU SRP
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