Comparison of toxicogenomics and traditional approaches to inform mode of action and points of departure in XXXX health risk assessment of @entity3014 in drinking water.

@entity1 @entity35125 @entity40007 @entity19 @entity3014 @entity3015 @entity35126
Toxicogenomics is proposed to be a useful tool in @entity1 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 @entity3014 ( @entity3015 ), a well-studied carcinogen, for drinking water exposures. Our study was intended to compare methodologies, not to evaluate drinking water safety. We compared traditional ( @entity35125 ), genomics-informed ( @entity35126 ) and genomics-only ( @entity40007 ) approaches. @entity35126 and @entity40007 applied toxicogenomics data from @entity1 cell cultures and @entity19 exposed to @entity3015 to determine if these data could provide insight into @entity3015 's mode of action (MOA) and derive tissue-specific points of departure (POD). Our global gene expression analysis supported that @entity3015 is genotoxic in @entity19 and allowed the development of a detailed MOA. Toxicogenomics analysis in @entity1 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). @entity40007 , 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.
