Toxicogenomics - What added Value Do These Approaches Provide for Carcinogen Risk Assessment?

It is still a major challenge to protect humans at workplaces and in the environment. To cope with this task, it is a prerequisite to obtain detailed information on the extent of chemical perturbations of biological pathways, in particular, adaptive vs. adverse effects and the dose-response relationships. This knowledge serves as the basis for the classification of non-carcinogens and carcinogens and for further distinguishing carcinogens in genotoxic (DNA damaging) or non-genotoxic compounds. Basing on quantitative dose-response relationships, points of departures can be derived for chemical risk assessment. In recent years, new methods have shown their capability to support the established rodent models of carcinogenicity testing. In vitro high throughput screening assays assess more comprehensively cell response. In addition, omics technologies were applied to study the mode of action of chemicals whereby the term "toxicogenomics" comprises various technologies such as transcriptomics, epigenomics, or metabolomics. This review aims to summarize the current state of toxicogenomic approaches in risk science and to compare them with established ones. For example, measurement of global transcriptional changes generates meaningful information for toxicological risk assessment such as accurate classification of genotoxic/non-genotoxic carcinogens. Alteration in mRNA expression offers previously unknown insights in the mode of action and enables the definition of key events. Based on these, benchmark doses can be calculated for the transition from an adaptive to an adverse state. In short, this review assesses the potential and challenges of transcriptomics and addresses the impact of other omics technologies on risk assessment in terms of hazard identification and dose-response assessment.