By Mel Andersen, Ph.D., Senior Program Advisor
It’s a grand time to be a toxicologist committed to using non-animal based biological and computational methods to assess the safety of chemicals and chemical products for human populations.
My toxicology career spans 48 years, with employment in the federal government, consulting firms, academia, and not-for-profit and for-profit companies. None of my career accomplishments means as much to me as my involvement in and commitment to the development and implementation of new alternative methods that are more relevant for assessing safety in human population and reduce the current reliance on animal testing.
Since the 1930’s, toxicity testing has relied on in-life studies in various species, primarily rats and mice. Over time, there has been debate about the value of these studies for predicting human responses under different exposure situations, as well as concerns for the humane use of animals. In 1959, Russell and Burch’s “The Principles of Humane Experimental Technique” was published, which introduced the 3 Rs – Refinement, Reduction and Replacement. However, the decades following publication of this book saw large increases in toxicity testing due to an increasing number of chemicals in commerce and the appearance of new in-life test methods for various health endpoints (e.g. cancer, neurodevelopment, reproduction, endocrine, etc.) Approaches to risk assessment, i.e., the use of this information for decision making, also evolved, but still relied heavily on dose-response relationships from these animal studies. By the end of the 20th century, testing became even more expensive and used larger and larger numbers of animals.
At the same time, new opportunities could be envisioned due to the increased knowledge of biology, new platforms for testing in human cells and automation of methods that allowed for testing of much larger numbers of compounds. From 2004 through 2007, a National Academy of Sciences Committee produced a landmark report, “Toxicity Testing in the 21st Century: A Vision and A Strategy”, that outlined prospects for a fundamental redirection away from in life testing to evaluations of biological activities of compounds using simpler test systems – some purely computationally based and others using high throughput testing with cell extracts and cellular systems, stressing the use of testing with human-derived materials. I was a member of this committee and, with other committee members, wrote several articles about the report. Overall, the report received mixed reviews, with almost all critiques noting that the goals were overly ambitious and unlikely to be reached anytime in the near future.
However, the engine of change had been in motion with contributions to next generation methods appearing throughout the world from government, academic and industry. Large multi-stakeholder approaches were pursued in Europe, Canada and the United States. In Europe, a good deal of progress was provoked by EU legislation that prohibited the use of animals in safety testing for cosmetics. Both the USEPA and Health Canada developed plans for using so-called new approach methodologies (NAMs) for risk assessment. In a bold step forward, the US Environmental Protection Agency on Sept 10, 2019 announced plans to stop conducting or funding toxicity testing in living mammals by 2035. This commitment from the US EPA shows the value, progress and recognized promise of the many NAMs under development.
As toxicology becomes committed to moving away from in-life testing, there is a pressing need to build scientifically sound approaches and guidance on best use NAMs to inform chemical safety questions. Here at ScitoVation, our commitment to the risk assessment community is to continue to be a pioneer in developing NAMs and helping stakeholders in implementing their use to bring safe products to market faster. Industry and other chemical safety stakeholders will need to continue to work together to realize the goals set forth by the US EPA while ensuring the standard of human and environmental health protection to which we are accustomed.
Mel Andersen, Ph.D.
Senior Program Advisor at ScitoVation LLC