May 1, 2018: Advancing Chemical Testing for the 21st Century

“Chemicals” are sometimes thought of as being universally detrimental to health, with the possible exception of “natural” chemicals. In fact, the word “chemical” describes a vast universe of millions of molecules, both naturally occurring and man-made, that can have beneficial effects (like penicillin or vitamin C) or toxic ones (like carbon monoxide or dioxin). Further, most chemicals — even pure water — can be toxic if consumed in large enough quantities.

Our inability to predict whether a new chemical might cause adverse health effects at doses people are normally exposed to is one of the greatest causes of translational failure in drug development and uncertainty in environmental health. Remarkably, our methods for evaluating the safety (or its opposite, toxicity) of chemicals have changed little over the past 50 years due to technical barriers and appropriate caution about protecting public health. But beginning about 10 years ago, this began to change as NIH and several other federal agencies joined together in an unprecedented collaboration to drive toxicity testing into the 21st century. This ambitious vision required better methods to rapidly and efficiently evaluate the safety of environmental chemicals, pesticides, food additives and drugs.

Established in 2008, the Toxicology in the 21st Century (Tox21) program became part of NCATS when our Center was launched in fiscal year 2012. Through the program, scientists have developed and validated new high-throughput screening assays (tests) and generated and made public data on tens of thousands of chemicals; for many of them, there had been no information about potential toxic side effects. These data are now beginning to inform regulatory decisions about safety.

Tox21-supported advances are remarkable and have transformed how chemicals are evaluated for their potential effects on human health. But the work is just beginning, since these successes also have enabled a greater understanding of key obstacles that must be overcome to achieve our original vision. These roadblocks include technical and biological limitations of current methods, as well as barriers to efficiently translating screening results into regulatory decision making.

To address these challenges, Tox21 partners from NCATS, the National Toxicology Program at NIH’s National Institute of Environmental Health Sciences, the Environmental Protection Agency, and the Food and Drug Administration have released a new strategic and operational plan that expands the program’s research activities. The plan shifts Tox21’s primary focus from screening libraries of chemicals to follow-up studies that address specific focus areas, using a new type of cross-partner project.

There are many examples of how discoveries from Tox21 are informing new research directions. For instance, in a previous message I discussed how Tox21 scientists had screened cells from a group of genetically diverse people and demonstrated that individual responses to many chemicals varied much more than previously thought. One of the five new focus areas for Tox21 will address genetic variability between different groups of people by creating alternative test systems. This approach could further improve the predictive power of chemical evaluations and identify populations that are especially susceptible to certain substances.

Tox21 is just one example of NCATS’ success in developing entirely new paradigms that are making translation more efficient and effective through collaboration, new operational models and smarter science.

Christopher P. Austin, M.D.
Director
National Center for Advancing Translational Sciences