Companies and governments around the world can now use a new nonanimal approach to identify skin sensitizers. NIEHS researchers and collaborators developed a guideline describing this approach, which was published June 14 by the Organisation for Economic Co-operation and Development (OECD).

Skin sensitizers are chemicals that can cause allergic skin reactions. Acceptance of the approach by OECD and its incorporation into a guideline represent major achievements. This is the first internationally harmonized guideline to describe a nonanimal method that can be used to replace an animal test to identify skin sensitizers.

The National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods(https://ntp.niehs.nih.gov/pubhealth/evalatm/) (NICEATM) led the project to develop the OECD guideline and worked with other U.S. government agencies as well as scientists from Canada and the European Union to sponsor the guideline.

NICEATM conducts data analyses, workshops, independent validation studies, and other activities to assess new, revised, and alternative test methods and strategies. (Photo courtesy of Shutterstock.com)

Once the non-animal approach was developed, NICEATM collaborated with colleagues at the German Federal Institute for Risk Assessment to assemble a set of human skin sensitization test data to support the OECD guideline. This data set was used to evaluate the new approach and demonstrate that it predicts human effects better than the currently accepted animal test.

Reducing animal use internationally

NICEATM scientists actively participate in international projects to reduce animal use for identifying skin sensitizers. The project to develop the new OECD guideline began at a 2016 workshop of the International Cooperation on Alternative Test Methods(https://ntp.niehs.nih.gov/go/icatm) (ICATM). NICEATM is a founding member and active participant in ICATM.

Development of the new international guideline was a goal stated in the workshop report, which specified that such a guideline should describe a “defined approach” to identify chemical skin sensitizers. A defined approach is a structured, reproducible method to combine several types of data to arrive at a conclusion about a chemical’s hazard.

“A defined approach guideline is a new kind of product for OECD,” commented acting NICEATM Director Nicole Kleinstreuer, Ph.D., who strove for years to gain acceptance of the standard. “We hope that this guideline will pave the way for similar approaches to be developed for endpoints such as eye and skin irritation.”

With publication of this non-animal approach in an OECD guideline, data generated from its use must be accepted by regulatory agencies in OECD member countries. As noted at a recent NICEATM-sponsored public forum(https://ntp.niehs.nih.gov/go/iccvamforum-2021), international agreement on such methods is key to reducing animal use.

Human data confirms predictions

For some testing applications, questions often arise about how well animals represent human biology. NICEATM’s collaboration with their German colleagues created a reliable set of human data to evaluate the defined approach. Having human data for an endpoint allows comparison of how well a new nonanimal method predicts human hazard with how well an accepted animal test predicts the same hazard.

NICEATM compared predictions of human hazard obtained from the defined approach and from the established animal test to results of human allergy tests on the same chemicals. They found that the defined approach predicted human effects better than the accepted animal test.

U.S. agencies embrace defined approaches

NICEATM has been advancing alternatives for skin sensitization(https://ntp.niehs.nih.gov/go/ACDtest) testing throughout its 20-year history. The center works with U.S. federal regulatory agencies to apply those advancements to testing requirements.

Several collaborations between NICEATM and the U.S. Environmental Protection Agency have resulted in that agency accepting data from nonanimal defined approaches as a replacement for data from animals for required skin sensitization tests.

(Catherine Sprankle is a communications specialist for ILS, the contractor supporting NICEATM.)