title: Technical guide for applications of gene expression profiling in human health risk assessment of environmental chemicals.
abstract: Toxicogenomics promises to be an important part of future human health risk assessment of environmental chemicals. The application of gene expression profiles (e.g., for hazard identification, chemical prioritization, chemical grouping, mode of action discovery, and quantitative analysis of response) is growing in the literature, but their use in formal risk assessment by regulatory agencies is relatively infrequent. Although additional validations for specific applications are required, gene expression data can be of immediate use for increasing confidence in chemical evaluations. We believe that a primary reason for the current lack of integration is the limited practical guidance available for risk assessment specialists with limited experience in genomics. The present manuscript provides basic information on gene expression profiling, along with guidance on evaluating the quality of genomic experiments and data, and interpretation of results presented in the form of heat maps, pathway analyses and other common approaches. Moreover, potential ways to integrate information from gene expression experiments into current risk assessment are presented using published studies as examples. The primary objective of this work is to facilitate integration of gene expression data into human health risk assessments of environmental chemicals.
authors.affiliation: Water and Air Quality Bureau, Health Canada, Ottawa, ON, Canada.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Bourdon-Lacombe
authors.affiliation: Water and Air Quality Bureau, Health Canada, Ottawa, ON, Canada. Electronic address: Ivy.Moffat@hc-sc.gc.ca.
authors.forename: Ivy D
authors.initials: ID
authors.lastname: Moffat
authors.affiliation: Water and Air Quality Bureau, Health Canada, Ottawa, ON, Canada.
authors.forename: Michelle
authors.initials: M
authors.lastname: Deveau
authors.affiliation: Environmental Health Science and Research Bureau, Health Canada, Ottawa, ON, Canada.
authors.forename: Mainul
authors.initials: M
authors.lastname: Husain
authors.affiliation: Biomolecular Screening Branch, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, United States.
authors.forename: Scott
authors.initials: S
authors.lastname: Auerbach
authors.affiliation: McLaughlin Centre for Population Health Risk Assessment, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Krewski
authors.affiliation: National Centre for Computational Toxicology, U.S. Environmental Protection Agency, Research Triangle Park, NC, United States.
authors.forename: Russell S
authors.initials: RS
authors.lastname: Thomas
authors.affiliation: Biostatistics and Computational Biology Branch, Division of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, NC, United States.
authors.forename: Pierre R
authors.initials: PR
authors.lastname: Bushel
authors.affiliation: Environmental Health Science and Research Bureau, Health Canada, Ottawa, ON, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Williams
authors.affiliation: Environmental Health Science and Research Bureau, Health Canada, Ottawa, ON, Canada.
authors.forename: Carole L
authors.initials: CL
authors.lastname: Yauk
mesh_terms: D004785:Environmental Pollutants / Q000633:toxicity*; D020869:Gene Expression Profiling; D006801:Humans; D018570:Risk Assessment / Q000379:methods*; D043922:Toxicogenetics
chemical_list: D004785:Environmental Pollutants
keywords: Chemical mode of action; Hazard assessment; Human health risk assessment; Risk characterization; Toxicogenomics