Skip to main content
HHS Logo U.S. Department of Health & Human Services Divider arrow NIH logo National Institutes of Health Alt desc
Toxicology in the 21st Century

Tox21 Projects

Tox21 projects are made possible by new technologies and new discoveries in gene expression analysis, culture of human tissue stem cells and integrated pathway information.


Through this project, Tox21 researchers are working to annotate pathways by source, species, biological function/process, disease/toxicity relevance and availability of probing assays using data from the PubChem and ToxCast databases. Continued development of this resource will include compound activity data, sequence data, gene/protein expression data and pathway data from non-human species, in addition to organizing assays according to pathways/diseases/toxicity end points. This integrated platform will facilitate systematic analysis and modeling of toxicity responses.


Tox21 researchers work on a variety of different assays:

  • Apoptosis
  • ATAD5 (ELG1)
  • Caspase (measures activity of caspase 3/7, 8, 9)
  • Cell viability (measures ATP)
  • Cytotoxicity
  • Differential cytotoxicity (DNA damage repair gene–deficient cell lines, DT40 and mouse cell lines)
  • Genetic toxicology
  • Genetic variation: more than 1,000 HapMap lines
  • LDH and protease release
  • Membrane integrity
  • Micronucleus
  • Mitochondrial toxicity
  • Mitochondrial membrane potential
  • Phospholipidosis
  • Pathway-specific toxicological mechanisms: reporters (e.g., luciferase, β-lactamase) measuring hypoxia, ER stress, NFκB, P53, ARE, HSE, CREB, AP-1, STAT, NFAT, RSP
  • Target-specific toxicological mechanisms:
    • Nuclear receptors: AR, AhR, ERα, FXR, GR, LXR, PPARδ, PPARγ, PXR, RXR, TRβ, VDR, RORγ, CAR
    • hERG channel
    • Cytokine: IL-8, TNFα
    • Ca mobilization and influx