ToxCast and Tox21: High Throughput Screening for Hazard & Risk ...

Biochemical Assays
• Protein families
ToxCast HTS Assays
~500 Total Endpoints
Cellular Assays
• Cell lines
– HepG2 human hepatoblastoma
– GPCR
– A549 human lung carcinoma
– HEK 293 human embryonic y kidney y
– NR
– Kinase
• Primary cells
– Human endothelial cells
– Phosphatase
– Human monocytes
– Protease
– HHuman kkeratinocytes ti t
– Other enzyme
– Ion channel
– Transporter
– Human fibroblasts
– Human proximal tubule kidney cells
– Human small airway epithelial cells
– Rat hepatocytes p y
– Mouse embryonic stem cells (Sid Hunter)
• Assay formats
– Radioligand binding
– Enzyme activity
– Co-activator recruitment
Primarily Human / Rat
EException: ti ZZebrafish b fi h ddevelopment l t (St (Stephanie h i Padilla)
P dill )
Office of Research and Development
Computational Toxicology Research Program
• Biotransformation competent cells
– Primary rat hepatocytes
– Primary human hepatocytes
• Assay formats
– Cytotoxicity
– Reporter gene
– Gene expression
13
– Biomarker production
– High-content imaging for cellular phenotype