Chemicals are part of everyday life. They are found in common household and workplace products including food, packaging, paint and dyes, cleaning supplies, medicines, among many other categories of products. Yet, only a small number of chemicals have been thoroughly assessed for their potential toxicity in humans. Furthermore, there are an increasing number of commercially available chemicals continually making their way into our food and environment.
Approximately ten years ago, a collaboration among government agencies came together to form the Toxicology in the 21st Century program. Tox21, as it came to be known, sought to develop more effective and efficient approaches to more reliably predict how chemicals may affect human health. The participating institutions include:
- National Center for Advancing Translational Sciences,
- National Toxicology Program (NTP)
- National Center for Computational Toxicology
- Food and Drug Administration (FDA) and
- Environmental Protection Agency (EPA).
Why should Tox 21 matter to litigators?
As we move into the 21st Century, new toxicity data will be uncovered at a rapid rate, which may catch manufacturers and consumers off-guard. Historically, toxicological testing of chemicals was slow, expensive, and a resource-intensive activity that would turn out data not necessarily relevant to humans. With newer technologies (high-throughput screens, for instance), Tox21 testing will uncover new findings on thousands of chemicals in days or weeks.
Below are five reasons we believe that attorneys and manufacturers in the chemical industry should be aware of Tox 21.
1. More Information on More Chemicals in Less Time
Tox 21 employs large-scale, high-throughput robotic screening to simultaneously test thousands of chemicals. The Tox21 chemical library includes more than 10,000 compounds, including industrial and consumer products, food additives, drugs, and chemical mixtures, and prioritizes specific compounds for more extensive evaluation. The results will provide information regarding chemical safety and dose-response relationships for better risk management. Attorneys will see a significant increase in the volume and complexity of toxicological information they are presented with, and as a result will need to adopt new strategies to convincingly communicate this information in the courtroom. Gina Solomon, a senior scientist with the Natural Resources Defense Council summed it up in a piece describing the Tox21 initiative:
“Your average person on the street understands that when something causes birth defects in a rat, that’s something for humans to be concerned about … But when you base [arguments] on perturbations of thyroid hormone homeostasis, well, it’s going to be harder for the public to know what to think about that.”
2. Automation is Efficient and Accurate
Traditional animal models are time consuming and the results do not always translate to real-life human exposure. Tox 21’s target-specific screening and informatics systems will identify serious gene-pathway interactions in vitro that are not easily detected in whole animal models, which will result in data that are more relevant to real-life human exposures. But in vitro toxicological data alone cannot prove causation in vivo, and are only useful to the extent that the plaintiff’s exposure resembles testing conditions. Over-interpretation or misinterpretation of data could lead to inappropriate conclusions regarding the toxicity of a chemical. For these reasons, it is imperative that anyone presenting or evaluating toxicological evidence in the courtroom is versed in the principles, methods, and limitations of toxicological studies.
3. Increased Understanding of Genetic Influence on Toxicological Outcomes
To date, Tox 21 partners have identified approximately 2,800 genes in human cells and tissues that may be “environmentally responsive” to toxic chemicals following exposure. In 2015, the team found that for about half of the chemicals tested, the range of genetic variability and susceptibility differences among tested individuals was larger than previously assumed. Individual variability underlies the extent to which people respond to chemical exposure, as well as genetic susceptibility to toxicity. Recognizing individual differences will be a key consideration in risk assessment.
4. Linking Specific Pathways to Adverse Biological Outcomes
Although scientific advances have identified factors to consider when evaluating adverse health outcomes, such as differential effects of dosing, timing, and duration of exposure, current methods provide little information on how chemicals act on biochemical processes. Tox 21 researchers are working to identify cellular pathways that, when compromised, may lead to adverse health consequences. The goal is to predict toxicity by measuring pathways’ interactions with various chemicals and the resulting pattern of biological response. Such elucidation of specific pathways may make the link between specific chemicals and adverse health outcomes more difficult to call into question.
5. Broad Access to Chemical Data for Risk Assessment
Whereas toxicological data was once a bit removed from the average lawyer, Tox21 is making the data more accessible. The longer-term goal of Tox 21 efforts is to develop a reference database of chemical effects in biological systems that can be used to define common mechanisms of action, chemical and drug interactions, and cellular pathways of response, toxicity, and harmful consequences. Testing will not only determine if chemical exposure has the potential for adverse events, but link specific biological events to the adverse outcomes, providing a readily accessible basis for risk assessment.
Tox 21 Data in the Real World
The EPA‘s Endocrine Disruption Screening Program is using Tox 21 assays to identify chemicals that have the potential for estrogenic activity which could lead to endocrine disruption. Indeed, The Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) recently concluded a meeting (November 28-30, 2017) to discuss and review Alternative High-Throughput Screens to Determine Endocrine Disruption, Focusing on Androgen Receptor, Steroidogenesis, and Thyroid Pathways. Beyond the EPA, the European Chemicals Agency also references Tox 21 assays for identifying potential endocrine disrupting chemicals.
The California EPA has incorporated Tox 21 data in select pesticide assessments, and the Minnesota Department of Health is using Tox 21 data for assessing health risks associated with water contaminants. The World Health Organization’s International Agency for Research on Cancer has used Tox21 data as one area of evidence for assessing the evidence of carcinogenesis. Tox 21 tests have been used to evaluate the toxicity of the chemicals and dispersants in the 2010 Deepwater Horizon BP Gulf spill and 2014 West Virginia Elk River spill.
Tox 21 represents a paradigm shift for toxicology and risk assessment. The program’s high-throughput testing methods will enable faster and more efficient evaluation of chemicals’ effects on human health. The focus on pathways means that someday scientists will predict potential harm based on how chemicals activate toxicity in cells. Understanding the relationship between the dose in which a person has been exposed and the underlying pathways linked to toxicity is crucial in determining whether an event in question could have caused suspected harm. The challenge for attorneys becomes to first understand the whether and how the science supports their position, and second to make a comprehensible and compelling case to judges and juries.