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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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

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