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2947764 
Journal Article 
Review 
Comparison of toxicogenomics and traditional approaches to inform mode of action and points of departure in human health risk assessment of benzo[a]pyrene in drinking water 
Moffat, I; Chepelev, NL; Labib, S; Bourdon-Lacombe, J; Kuo, B; Buick, JK; Lemieux, F; Williams, A; Halappanavar, S; Malik, AI; Luijten, M; Aubrecht, J; Hyduke, DR; Fornace, AJ; Swartz, CD; Recio, L; Yauk, CL 
2015 
Yes 
Critical Reviews in Toxicology
ISSN: 1040-8444
EISSN: 1547-6898 
TAYLOR & FRANCIS LTD 
ABINGDON 
45 
1 
1-43 
English 
25605026 
WOS:000348199100001 
Toxicogenomics is proposed to be a useful tool in human health risk assessment. However, a systematic comparison of traditional risk assessment approaches with those applying toxicogenomics has never been done. We conducted a case study to evaluate the utility of toxicogenomics in the risk assessment of benzo[a]pyrene (BaP), a well-studied carcinogen, for drinking water exposures. Our study was intended to compare methodologies, not to evaluate drinking water safety. We compared traditional (RA1), genomics-informed (RA2) and genomics-only (RA3) approaches. RA2 and RA3 applied toxicogenomics data from human cell cultures and mice exposed to BaP to determine if these data could provide insight into BaP's mode of action (MOA) and derive tissue-specific points of departure (POD). Our global gene expression analysis supported that BaP is genotoxic in mice and allowed the development of a detailed MOA. Toxicogenomics analysis in human lymphoblastoid TK6 cells demonstrated a high degree of consistency in perturbed pathways with animal tissues. Quantitatively, the PODs for traditional and transcriptional approaches were similar (liver 1.2 vs. 1.0 mg/kg-bw/day; lungs 0.8 vs. 3.7 mg/kg-bw/day; forestomach 0.5 vs. 7.4 mg/kg-bw/day). RA3, which applied toxicogenomics in the absence of apical toxicology data, demonstrates that this approach provides useful information in data-poor situations. Overall, our study supports the use of toxicogenomics as a relatively fast and cost-effective tool for hazard identification, preliminary evaluation of potential carcinogens, and carcinogenic potency, in addition to identifying current limitations and practical questions for future work. 
benchmark dose; carcinogens; dose-response; environmental pollutant; genomics; human health risk assessment; mode of action; point of departure; polycyclic aromatic hydrocarbon; transcriptomics