The Next Generation of Risk Assessment Multi-Year Study-Highlights of Findings, Applications to Risk Assessment, and Future Directions.
BACKGROUND
The Next Generation (NexGen) of Risk Assessment effort is a multi-year collaboration among several organizations evaluating new, potentially more efficient molecular, computational, and systems biology approaches to risk assessment. This article summarizes our findings, suggests applications to risk assessment, and identifies strategic research directions.


OBJECTIVE
Our specific objectives were to test whether advanced biological data and methods could better inform our understanding of public health risks posed by environmental exposures.


METHODS
New data and methods were applied and evaluated for use in hazard identification and dose-response assessment. Biomarkers of exposure and effect, and risk characterization were also examined. Consideration was given to various decision contexts with increasing regulatory and public health impacts. Data types included transcriptomics, genomics, and proteomics. Methods included molecular epidemiology and clinical studies, bioinformatic knowledge mining, pathway and network analyses, short-duration in vivo and in vitro bioassays, and quantitative structure activity relationship modeling.


CONCLUSIONS
NexGen has advanced our ability to apply new science by more rapidly identifying chemicals and exposures of potential concern, helping characterize mechanisms of action that influence conclusions about causality, exposure-response relationships, susceptibility and cumulative risk, and by elucidating new biomarkers of exposure and effects. Additionally, NexGen has fostered extensive discussion among risk scientists and managers and improved confidence in interpreting and applying new data streams.


CONCLUSIONS
While considerable uncertainties remain, thoughtful application of new knowledge to risk assessment appears reasonable for augmenting major scope assessments, forming the basis for or augmenting limited scope assessments, and for prioritization and screening of very data limited chemicals. Citation: Cote I, Andersen ME, Ankley GT, Barone S, Birnbaum LS, Boekelheide K, Bois FY, Burgoon LD, Chiu WA, Crawford-Brown D, Crofton KM, DeVito M, Devlin RB, Edwards SW, Guyton KZ, Hattis D, Judson RS, Knight D, Krewski D, Lambert J, Maull EA, Mendrick D, Paoli GM, Patel CJ, Perkins EJ, Poje G, Portier CJ, Rusyn I, Schulte PA, Simeonov A, Smith MT, Thayer KA, Thomas RS, Thomas R, Tice RR, Vandenberg JJ, Villeneuve DL, Wesselkamper S, Whelan M, Whittaker C, White R, Xia M, Yauk C, Zeise L, Zhao J, DeWoskin RS. 2016. The Next Generation of Risk Assessment multiyear study-highlights of findings, applications to risk assessment, and future directions. Environ Health Perspect 124:1671-1682; http://dx.doi.org/10.1289/EHP233.
National Center for Environmental Assessment, U.S. Environmental Protection Agency (EPA), Washington, District of Columbia, USA.
Ila
I
Cote
Melvin E
ME
Andersen
Gerald T
GT
Ankley
Stanley
S
Barone
Linda S
LS
Birnbaum
Kim
K
Boekelheide
Frederic Y
FY
Bois
Lyle D
LD
Burgoon
Weihsueh A
WA
Chiu
Douglas
D
Crawford-Brown
Kevin M
KM
Crofton
Michael
M
DeVito
Robert B
RB
Devlin
Stephen W
SW
Edwards
Kathryn Z
KZ
Guyton
Dale
D
Hattis
Richard S
RS
Judson
Derek
D
Knight
Daniel
D
Krewski
Jason
J
Lambert
Elizabeth Anne
EA
Maull
Donna
D
Mendrick
Gregory M
GM
Paoli
Chirag Jagdish
CJ
Patel
Edward J
EJ
Perkins
Gerald
G
Poje
Christopher J
CJ
Portier
Ivan
I
Rusyn
Paul A
PA
Schulte
Anton
A
Simeonov
Martyn T
MT
Smith
Kristina A
KA
Thayer
Russell S
RS
Thomas
Reuben
R
Thomas
Raymond R
RR
Tice
John J
JJ
Vandenberg
Daniel L
DL
Villeneuve
Scott
S
Wesselkamper
Maurice
M
Whelan
Christine
C
Whittaker
Ronald
R
White
Menghang
M
Xia
Carole
C
Yauk
Lauren
L
Zeise
Jay
J
Zhao
Robert S
RS
DeWoskin
D004784:Environmental Monitoring / Q000379:methods*; D004785:Environmental Pollutants / Q000633:toxicity; D011634:Public Health / Q000379:methods / Q000639:trends; D018570:Risk Assessment / Q000379:methods* / Q000639:trends
D004785:Environmental Pollutants