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Toxicogenomics refers to the application of omics approaches for the investigation of molecular alterations that occur in response to hazardous substances. High-throughput, unbiased screening tools, such as omics techniques, are gaining a prominent role in the safety assessment of chemicals, as they can provide valuable information to the risk assessor, whilst facilitating the implementation of the 3Rs principle (replacement, reduction and refinement of animal use). This chapter explores the current and potential utilisation of toxicogenomics within the key steps of risk assessment, focusing on aspects and challenges specific to food safety. Selected food contaminants and ingredients are discussed as historical case studies to inform the development of non-animal approaches to risk assessment.

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