Doug Johns1

Janice S. Lee1

Mentors: Bob Sonawane1, Jackie Moya1,
Tom McCurdy2, Vernon Benignus3
'NCEA, Washington, DC;

2NERL 3NHEERL, Research Triangle Park, NC

Agpng

[initiative

Environmental Exposures and Health Implications in Older Adults

Mentors: Chris Corton1, Mike Devito1, Mike Tornero2
1NHEERL, 2NERL, Research Triangle Park, NC

Building realistic biologically-based pharmacokinetic models
for predicting susceptibility in aged populations

Research Goal: Provide a more complete understanding of
environmental exposures and the associated health risks in aging
populations

Research Goal: Improve pharmacokinetic models of the aged by
incorporating genomic information on the differences in xenobiotic
metabolism gene expression between young and old populations

Projects

•	Organize a workshop to discuss the aging as a susceptible
population in conducting risk assessments

•	Develop an Exposure Factors Handbook for the aging

•	Conduct a large scale review and analysis of age-related
changes in phase I, phase II, and antioxidant enzyme activities

•	Develop a PBPK model to predict the kinetic behavior of specific
neurotoxicants in older adults

Anticipated Outcome

This research will provide information that can be used by risk
assessors to characterize age-related changes in exposures to
environmental chemicals, and understand how the aging body
responds to toxic stressors

Hazard Identification *

Exposure Assessment

Risk Characterization

Risk Assessment Paradigm

Example of a physiologically
based toxicokinetic model for
an inhaled VOC.

Projects

•	Generate gene expression profiles for xenobiotic metabolizing
enzymes (XMEs) in the aging rat, mouse & human

•	Generate gene expression profiles in the aging rat, mouse & human
after exposure to toluene & other chemicals to determine changes in
XMEs

•	Incorporate genomic information in the construction and improvement
of a rodent & human PB-PK model for the aged

Anticipated Outcomes

•	Identification of common and disparate changes in XMEs during aging
between tissues and across species

•	Integration of XME gene expression behavior in PB-PK models of
different life stages that help to predict toxicity in different
subpopulations

AlTHNMIWOKtAM



Scanned image
Affymetrix chip

I0***]

mm

I

-—•! IK |

—EP

ra

rjrliwi

lis]	T m

J-

- ¦ fcs

|1AW I



~CSr-

Cluster analysis

Pathway analysis (KEGG)

-------