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

被引：68

作者：

Cote, Ila ^{[1
]}

Andersen, Melvin E. ^{[2
]}

Ankley, Gerald T. ^{[3
]}

Barone, Stanley ^{[4
]}

Birnbaum, Linda S. ^{[5
,6
]}

Boekelheide, Kim ^{[7
]}

Bois, FredericY. ^{[8
]}

Burgoon, Lyle D. ^{[9
]}

Chiu, Weihsueh A. ^{[10
]}

Crawford-Brown, Douglas ^{[11
]}

Crofton, Kevin M. ^{[12
]}

DeVito, Michael ^{[5
,6
]}

Devlin, Robert B. ^{[13
]}

Edwards, Stephen W. ^{[13
]}

Guyton, Kathryn Z. ^{[14
]}

Hattis, Dale ^{[15
]}

Judson, Richard S. ^{[12
]}

Knight, Derek ^{[16
]}

Krewski, Daniel ^{[17
]}

Lambert, Jason ^{[18
]}

Maull, Elizabeth Anne ^{[5
,6
]}

Mendrick, Donna ^{[19
]}

Paoli, Gregory M. ^{[20
]}

Patel, Chirag Jagdish ^{[21
]}

Perkins, Edward J. ^{[22
]}

Poje, Gerald ^{[23
]}

Portier, Christopher J. ^{[24
]}

Rusyn, Ivan ^{[10
]}

Schulte, Paul A. ^{[25
]}

Simeonov, Anton ^{[26
]}

Smith, Martyn T. ^{[27
]}

Thayer, Kristina A. ^{[5
,6
]}

Thomas, Russell S. ^{[12
]}

Thomas, Reuben ^{[28
]}

Tice, Raymond R. ^{[5
,6
]}

Vandenberg, John J. ^{[1
]}

Villeneuve, Daniel L. ^{[3
]}

Wesselkamper, Scott ^{[18
]}

Whelan, Maurice ^{[29
]}

Whittaker, Christine ^{[25
]}

White, Ronald ^{[30
]}

Xia, Menghang ^{[26
]}

Yauk, Carole ^{[31
]}

Zeise, Lauren ^{[32
]}

Zhao, Jay ^{[18
]}

DeWoskin, Robert S. ^{[1
]}

机构：

[1] US EPA, Natl Ctr Environm Assessment, Washington, DC 20460 USA

[2] ScitoVation, Res Triangle Pk, NC USA

[3] US EPA, Natl Hlth & Environm Effects Res Lab, Duluth, MN USA

[4] US EPA, Off Chem Safety & Pollut Prevent, Washington, DC 20460 USA

[5] NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA

[6] NIH, Natl Toxicol Program, DHHS, Res Triangle Pk, NC USA

[7] Brown Univ, Dept Pathol & Lab Med, Providence, RI 02912 USA

[8] Inst Natl Environm Ind & Risques, Unite Modeles Icotoxicol & Toxicol, Verneuil En Halatte, France

[9] US Army, Engineer Res & Dev Ctr, Res Triangle Pk, NC USA

[10] Texas A&M Univ, Coll Vet Med & Biomed Sci, Dept Vet Integrat Biosci, College Stn, TX USA

[11] Univ Cambridge, Dept Land Econ, Cambridge, England

[12] Natl Ctr Computat Toxicol, Res Triangle Pk, NC USA

[13] US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA

[14] Int Agcy Res Canc, Lyon, France

[15] Clark Univ, George Perkins Marsh Inst, Worcester, MA 01610 USA

[16] European Chem Agcy, Helsinki, Finland

[17] Univ Ottawa, McLaughlin Ctr Populat Hlth Risk Assessment, Ottawa, ON, Canada

[18] US EPA, Natl Ctr Environm Assessment, Cincinnati, OH 45268 USA

[19] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA

[20] Risk Sci Int, Ottawa, ON, Canada

[21] Harvard Med Sch, Dept Biomed Informat, Boston, MA USA

[22] US Army, Engineer Res & Dev Ctr, Vicksburg, MS USA

[23] Grant Consulting Grp, Washington, DC USA

[24] Environm Def Fund, Washington, DE USA

[25] Ctr Dis Control & Prevent, Natl Inst Occupat Safety & Hlth, Educ & Informat Div, Cincinnati, OH USA

[26] NIH, Natl Ctr Adv Translat Sci, DHHS, Bethesda, MD USA

[27] Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA

[28] Univ Calif San Francisco, Gladstone Inst, San Francisco, CA 94143 USA

[29] European Commiss Joint Res Ctr, Syst Toxicol Unit, Ispra, Italy

[30] Ctr Effect Govt, Washington, DE USA

[31] Hlth Canada, Environm Hlth Sci & Res Bur, Ottawa, ON, Canada

[32] Calif EPA, Off Environm Hlth Hazard Assessment, Oakland, CA USA

来源：

ENVIRONMENTAL HEALTH PERSPECTIVES | 2016年 / 124卷 / 11期

关键词：

ADVERSE OUTCOME PATHWAYS; BRONCHIAL EPITHELIAL-CELLS; THROUGHPUT SCREENING DATA; IN-VIVO HAZARD; ENVIRONMENTAL CHEMICALS; HUMAN HEALTH; GENE-EXPRESSION; POPULATION VARIABILITY; PREDICTIVE TOXICOLOGY; ESTROGEN-RECEPTOR;

D O I：

10.1289/EHP233

中图分类号：

X [环境科学、安全科学];

学科分类号：

08 ; 0830 ;

摘要：

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. 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.

引用

页码：1671 / 1682

页数：12

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