A long-term interagency effort has resulted in new methods for testing whether certain substances disrupt the body’s hormones, which are part of the endocrine system. Such endocrine-disrupting chemicals can contribute to a variety of human conditions, including diabetes, early puberty, and cancer.

In December, the U.S. Environmental Protection Agency (EPA) announced that it had validated several “new approach methodologies,” or NAMs, that will enable the agency to test endocrine disruptors faster, more efficiently, and less expensively than it can using animal models alone.

“It’s very much a landmark decision,” said Nicole C. Kleinstreuer, Ph.D., director of the National Toxicology Program’s Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM), which played an integral role in the effort.

The announcement represents the culmination of more than a decade of research, led by the EPA and supported by other agencies, including NIEHS and the U.S. Food and Drug Administration (FDA).

“These NAMs are really crucial to testing chemicals at the speed and scale that's needed to better protect human health and the environment,” said Jake Li, EPA's Deputy Assistant Administrator for Pesticide Programs.

Running interference

The EPA, FDA, and NIEHS helped to develop the new tests or assays, through the Endocrine Disruptor Screening Program established by law in 1998. “Thousands of chemicals people are exposed to every day, like the plasticizer Bisphenol A [BPA], can mimic or block the hormones in the tightly regulated and extremely sensitive endocrine system,” said Kleinstreuer, who is also the executive director of the Interagency Coordinating Committee for the Validation of Alternative Methods.

Yet the EPA has only been able to investigate a small number of substances for their potential to disrupt the way that estrogen, androgen, or thyroid hormones function in the body. That was partly because EPA required certain animal tests for screening chemicals, according to Li. Those screening assays can take up to six years to complete and cost $1 million per chemical.

To develop an alternative testing method, researchers at NICEATM created a reference database of chemicals known to interfere with the endocrine system in more than 700 peer-reviewed animal studies. They then evaluated tests conducted in the lab to determine how chemicals affected estrogen pathways and compared the results to the database. The results showed that the lab tests were 95% accurate when matched against animal studies. Similar efforts on androgen pathways showed a smaller but significant accuracy.

A new approach

The NICEATM researchers first published the outcome of their years-long investigation in 2015. Scientific advisory panels reviewed the data and the predictions to ensure transparency. After going through the regulatory processes, EPA published its research findings validating those tests in January, paving the way for the agency to use the new methodology, particularly when evaluating pesticides.

The lab efforts also showed that the new tests could help the EPA prioritize which chemicals to test based on how they compare to known endocrine disruptors. In the future, computer models and work on thyroid hormones could also be used to assess the potential potency of a chemical.

“These results from the Endocrine Disruptor Screening Program provide an excellent example of how a regulatory agency like the EPA is leading the charge in taking new approach methodologies and implementing them into regulatory decision frameworks,” said Kleinstreuer.

Citation: U.S. Environmental Protection Agency. 2023. Availability of New Approach Methodologies (NAMs) in the Endocrine Disruptor Screening Program (EDSP). EPA-HQ-OPP-2021-0756. Research Triangle Park, NC: U.S. Environmental Protection Agency.