The future of safety testing is faster, cheaper, and human-relevant.
Explore the RevolutionFor decades, our understanding of chemical safety has relied heavily on animal testing—a process that is time-consuming, costly, and often fails to predict effects in people. But a quiet revolution is underway. Toxicology in the 21st Century (Tox21) is transforming this field, shifting the paradigm from slow, animal-centric studies to rapid, automated testing of chemicals using robots and advanced computational models. This groundbreaking approach promises to swiftly and accurately ensure the safety of everything from household products to life-saving medicines. 1
Traditional methods are giving way to mechanistic-based testing focused on human biology.
The vision for a new approach was catalyzed by a pivotal report from the National Academy of Sciences, Toxicity Testing in the 21st Century: A Vision and a Strategy. This report laid the groundwork for a fundamental shift towards mechanistic-based testing—focusing on understanding how chemicals disrupt biological pathways in the human body at the cellular and molecular level. 1 5
National Center for Advancing Translational Sciences
National Toxicology Program
Environmental Protection Agency
Food and Drug Administration
The Tox21 strategy is built on several technological pillars that were once the realm of science fiction.
A unique collection of approximately 10,000 chemicals for standardized testing and consistent data. 1
| Tool/Resource | Function in Toxicology Research |
|---|---|
| High-Throughput Screening (HTS) Assays | Automated tests to rapidly measure the effects of thousands of chemicals on specific biological targets. 1 5 |
| Tox21 10K Chemical Library | A curated collection of ~10,000 compounds used for standardized toxicity testing across the consortium. 1 |
| qHTS (Quantitative HTS) Platform | A refined screening method that tests each chemical at multiple concentrations, providing more detailed data on its biological activity. 1 5 |
| Transcriptomics | Technologies like RNA sequencing that reveal post-exposure changes in the expression of thousands of genes. 5 |
| High-Throughput Toxicokinetics (HTTK) | Measures how the body absorbs, distributes, metabolizes, and excretes chemicals, linking external dose to internal effect. 5 |
| Virtual Tissue Models | Computer simulations that model how chemical perturbations can affect entire organs or biological systems. 5 |
Understanding how the Tox21 vision works in practice through automated, systematic screening.
Researchers propose specific biological assays to measure defined interactions, such as chemical binding to hormone receptors. 1
The robotic system precisely dispenses human cells or components into thousands of tiny wells on assay plates. 1
The robot adds unique chemicals from the Tox21 library to each well, testing at multiple concentrations. 1
Plates are incubated and scanned to measure outcomes like pathway activation or inhibition. 1
Algorithms analyze results to identify "hit" chemicals for further investigation. 1
| Assay Target | Potential Health Relevance |
|---|---|
| Estrogen Receptor (ER) | Disruption linked to reproductive issues and certain cancers |
| hERG Channel | Blockage can cause fatal heart arrhythmias |
| Mitochondrial Function | Impairment linked to organ toxicity (e.g., liver) |
| Genotoxicity | Activation can indicate carcinogenic potential |
| Chemical ID | ER Activity | hERG Inhibition | Priority |
|---|---|---|---|
| Chem-001 | High | Inactive | High |
| Chem-002 | Inactive | High | High |
| Chem-003 | Inactive | Inactive | Low |
| Chem-004 | Moderate | Inactive | Medium |
| Data Type | Description | Primary Use |
|---|---|---|
| Biochemical HTS Data | Measures interaction with specific proteins (e.g., receptors) | Identify mechanisms of action |
| Transcriptomic Data (HTTr) | Measures changes in gene expression across the genome | Understand broader cellular responses to stress |
| ToxCast Data | EPA's database of HTS results on thousands of chemicals | Prioritize chemicals for regulatory risk assessment 6 |
| ToxRefDB | Database of traditional animal toxicity studies | Validate HTS methods by comparing to known outcomes 6 |
The power of this approach was demonstrated when Tox21 researchers used these methods to identify environmental chemicals that could trigger the onset of premature puberty in girls, such as a compound commonly used in fragranced hygiene products. 1
The ongoing challenge is translating cellular activity to confident human risk predictions.
Future efforts will focus on refining complex computer simulations that can predict how an organ will respond to a chemical insult. 6
Integrating data to understand differential susceptibility—why some people are more vulnerable to chemical exposures than others. 5
The transformation of toxicology is a testament to the power of collaboration and innovation. By embracing robotics, genomics, and computational biology, the Tox21 program is not just making toxicology faster and cheaper—it is making it more relevant to human health, helping to build a safer world for everyone.