Environmental Factor – August 2025: NIEHS leads international guideline update on nonanimal testing

NIEHS scientists and collaborators recently played a lead role in updating an international guideline designed to expand the use of nonanimal approaches in chemical safety testing. The milestone update marks the first time a nonanimal method to predict the degree of a chemical’s toxic effects has gained international acceptance.

The updated guideline describes testing strategies known as defined approaches that combine multiple types of nonanimal testing methods to help predict whether chemicals in cosmetics, pesticides, and other consumer products are skin sensitizers before they are marketed to consumers. Chemicals that can cause allergic skin reactions, such as rashes, are called skin sensitizers.

The updated “Defined Approaches on Skin Sensitisation” guideline was published June 25 by the Organisation for Economic Co-operation and Development (OECD), a 38-country trade organization. Scientists in the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) led development of the updated guideline and the groundbreaking 2021 guideline, which was the first to outline approaches to replace animal use for regulatory characterization of skin sensitizers.

“This update will make it easier for more regulated companies to use these defined approaches,” said Helena Hogberg, Ph.D., acting director of NICEATM. “It will also allow data from defined approaches to be used in a broader range of regulatory contexts.”

Many common chemicals are skin sensitizers

The original guideline described two methods that combine data from multiple cell-based in vitro assays to predict whether a chemical is a skin sensitizer. These predictions match the accuracy of animal tests to identify chemicals that could cause allergic reactions in humans.

The updated guideline allows more types of in vitro assays to be used in the defined approaches. It also adds a new defined approach called SARA-ICE (Skin Allergy Risk Assessment – Integrated Chemical Environment) that provides a numerical prediction of a chemical’s skin sensitization potency.

NICEATM developed SARA-ICE in collaboration with the consumer products company Unilever. It is the first accepted defined approach that provides a potency estimate. Agencies such as the U.S Environmental Protection Agency and the U.S. Food and Drug Administration require such estimates be calculated in certain regulatory contexts.

Online tools broaden use of defined approaches

Although the defined approaches are internationally accepted by regulatory agencies — data generated according to OECD guidelines must be accepted by regulatory agencies in OECD member countries — adopting them can be challenging. For example, the data interpretation procedures set forth in defined approaches can be complex and applying them manually can be time-consuming or prone to error.

To address these challenges and support wider use of defined approaches, NICEATM has developed two open-access online tools. The DASS App allows users to enter their own data from in vitro tests, then uses the defined approach analysis procedures to predict whether chemicals are skin sensitizers. The DASS App includes the latest in vitro methods outlined in the updated guideline. NICEATM also created a separate web tool for researchers interested in using the SARA-ICE defined approach.