The use of evidence from high-throughput screening and transcriptomic data in human health risk assessments.

ABSTRACT

High throughput screening (HTS) and functional genomics (toxicogenomics) have opened new avenues in toxicity testing. Their advantages include the potential for developing short-term in vivo bioassays and in vitro assays in order to keep pace with the growing backlog of chemicals that need to be evaluated for potential human health risk. In addition, these approaches have the potential to address some of the difficulties that arise with interpreting traditional rodent bioassays, such as the relevance of apical outcomes induced by chemical exposure in animals to humans. The wealth of information associated with the HTS and toxicogenomic data can inform human health risk assessment primarily through (i) insight into potential mechanism of action, (ii) prediction of adverse outcomes of chemical exposures, and (iii) dose-response assessment for derivation of toxicity values. In this article we outline current and expected future progress in these three directions and argue for increased role of HTS and toxicogenomic data in chemical risk assessment. We conclude that these approaches can help fulfill the NRC vision for toxicity testing in the 21st century and we discuss specific examples of chemicals whose health assessments can potentially benefit from available HTS or toxicogenomic data.