The Next Generation of Risk Assessment Multiyear Study- Highlights of Findings, Applications to Risk Assessment and Future Directions.

Cote I1, Andersen ME2, Ankley GT3, Barone S4, Birnbaum LS5, Boekelheide K6, Bois FY7, Burgoon LD8, Chiu WA9, Crawford-Brown D10, Crofton KM11, DeVito M5, Devlin RB12, Edwards SW12, Guyton KZ13, Hattis D14, Judson RS11, Knight D15, Krewski D16, Lambert J17, Maull EA5, Mendrick D18, Paoli GM19, Patel CJ20, Perkins EJ21, Poje G22, Portier CJ23, Rusyn I9, Schulte PA24, Simeonov A25, Smith MT26, Thayer KA5, Thomas RS11, Thomas R27, Tice RR5,Vandenberg JJ1, Villeneuve DL3, Wesselkamper S17, Whelan M28, Whittaker C24, White R29, Xia M25, Yauk C30, Zeise L31, Zhao J17, DeWoskin RS1.

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Abstract

BACKGROUND:

The Next Generation (NexGen) of Risk Assessment effort is a multiyear collaboration among several organizations evaluating new, potentially more efficient molecular, computational and systems biology approaches to risk assessment. This paper 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.

DISCUSSION:

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.