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2944147 
Journal Article 
Review 
Integrating toxicogenomics into human health risk assessment: lessons learned from the benzo[a]pyrene case study 
Chepelev, NL; Moffat, ID; Labib, S; Bourdon-Lacombe, J; Kuo, B; Buick, JK; Lemieux, F; Malik, AI; Halappanavar, S; Williams, A; Yauk, CL 
2015 
Yes 
Critical Reviews in Toxicology
ISSN: 1040-8444
EISSN: 1547-6898 
TAYLOR & FRANCIS LTD 
ABINGDON 
45 
1 
44-52 
English 
25605027 
WOS:000348199100002 
The use of short-term toxicogenomic tests to predict cancer (or other health effects) offers considerable advantages relative to traditional toxicity testing methods. The advantages include increased throughput, increased mechanistic data, and significantly reduced costs. However, precisely how toxicogenomics data can be used to support human health risk assessment (RA) is unclear. In a companion paper ( Moffat et al. 2014 ), we present a case study evaluating the utility of toxicogenomics in the RA of benzo[a]pyrene (BaP), a known human carcinogen. The case study is meant as a proof-of-principle exercise using a well-established mode of action (MOA) that impacts multiple tissues, which should provide a best case example. We found that toxicogenomics provided rich mechanistic data applicable to hazard identification, dose-response analysis, and quantitative RA of BaP. Based on this work, here we share some useful lessons for both research and RA, and outline our perspective on how toxicogenomics can benefit RA in the short- and long-term. Specifically, we focus on (1) obtaining biologically relevant data that are readily suitable for establishing an MOA for toxicants, (2) examining the human relevance of an MOA from animal testing, and (3) proposing appropriate quantitative values for RA. We describe our envisioned strategy on how toxicogenomics can become a tool in RA, especially when anchored to other short-term toxicity tests (apical endpoints) to increase confidence in the proposed MOA, and emphasize the need for additional studies on other MOAs to define the best practices in the application of toxicogenomics in RA. 
benchmark dose; carcinogens; dose-response; environmental pollutant; genotoxicity; mode of action; point of departure; polycyclic aromatic hydrocarbon