New Approach Methodologies Should Adhere to TSCA Standards

What’s New?

EPA recently asked its Board of Scientific Counselors (BOSC), comprised of experts in the fields of toxicology and environmental chemistry, to make recommendations on implementing new approach methods (NAMs) for testing the safety of new chemicals.

NAMs encompass a wide array of new evaluation strategies, including testing cell lines or invertebrates (rather than mammals); using computational approaches; and estimating potential harms of new chemicals by looking at existing toxicity data on similar substances.

Why It Matters

EPA announced in 2019 that it would be redirecting resources towards developing NAMs to replace those studies. The looming concern is the possibility that NAMs may miss effects that whole animal mammalian testing accounts for and generate false negatives — potentially allowing toxic chemicals to appear in consumer products or end up in our environment.

This could happen because relying only on NAMs or using data from one chemical to predict how a new one might behave opens the door to missing negative effects. NAMs could also cause evaluators to miss opportunities to use the Toxic Substances Control Act (TSCA), the nation’s primary chemical safety law, to limit toxic chemical exposures.

Rodents v. Algorithms?

Historically, new chemicals have been tested in whole animals (usually rodents) to determine if those substances are safe for humans. For example, current neurotoxicity testing relies on assessing the whole rodent brain to determine whether a chemical is neurotoxic.

NAMs, on the other hand, rely on the use of rapid or early response to predict longer-term impact(s) such as disease. For example, NAMs that use human cell lines can allow researchers to evaluate neurotoxicity by studying activity in human neural networks and at synapses.

Weighing the Pros & Cons of NAMs


  • Rapid evaluation of more chemicals at a lower cost: This could make it possible to test older chemicals that are already in use which may need to be reevaluated.
  • Improve and vastly increase the amount of data generated for use in decision making (van der Zalm et al. 2022) 


  • High false negative rates: Recent studies show that false negatives can occur up to 15% of the time in certain NAMs (Carstens et al. 2022). While animal tests can also produce inaccurate data, they do account realistically for metabolism and other changes that cannot be measured in vitro (Kleinstreuer et al. 2018a, b).
  • Difficulties with estimating chemical toxicity in complex situations: Evaluating chemical exposure during pregnancy or the way the body metabolizes chemicals after exposure. 

The Challenge Ahead

Given the current scientific landscape, we see certain challenges with adopting NAMs for all chemical toxicity studies:

  • Selecting the proper NAMs for different effects that may follow chemical exposure (e.g., toxicity to the developing brain, interference with hormone signaling)—and doing so in a timely manner.
  • Predicting potential longer-term effects from chemical exposures using NAMs.
  • Continuing to scrutinize new chemicals appropriately as we transition from mammalian testing to potentially using NAMs exclusively.
  • Improving in vitro analyses so that they are validated and standardized, perform at least as well as in vivo analyses, and account for metabolic changes that can sometimes prolong or change a chemical’s toxicity.

There is a lot of room for growth with NAMs but addressing these challenges will be critical if we are to move forward responsibly with a NAMs-only regulatory approach.

Our Take

EDF agrees with EPA’s BOSC that it is critical to identify NAMs that are fit for purpose and that reliably detect chemicals hazardous to humans—especially vulnerable populations like children, pregnant people, etc.—and the environment. Communities near the factories that produce those chemicals are particularly at higher risk of exposure. It is crucial that we err on the side of caution when making decisions about which chemicals to approve for use in the products we use, the cars we drive, and the toys our children play with and that may end up in our environment.

To do this successfully, we need better, faster approaches to ensure proper safety evaluations of new chemicals. However, we must ensure that testing aligns with TSCA. Ultimately, any new testing approaches must demonstrate the same quality and rigor as those we have used so successfully up to now—and false negatives must be minimized to the greatest extent possible.

Next Steps

Uniting approaches between the U.S. and the European Union—under frameworks proposed by the Organization for Economic Cooperation and Development and the International Cooperation on Alternative Testing Methods—will help EPA move forward in a manner consistent with other entities globally. By supporting cooperation and collaboration as we enter a new era for regulatory decisions, we will continue to protect vulnerable populations, such as fence line communities, and shield society and the environment from unnecessary exposure to chemicals that shorten lifespans and poison our planet.






















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