New OECD Guideline (TG 497) Provides Defined Approaches for Skin Sensitisation Without Animal Testing

Chemical companies can now extract potency information using a combination of several non-animal testing methods

On June 22, the Organisation for Economic Co-operation and Development (OECD) published a new skin sensitisation assessment guideline, the Defined Approaches (DA) for Skin Sensitisation (TG 497), in their Guidelines for the Testing of Chemicals, which contain around 150 internationally agreed-upon testing methods used by government, industry, and independent laboratories to characterize potential skin sensitisation chemical hazards. Regulatory bodies around the world, including the European Union, the U.S. Food & Drug Administration, and the U.S. Environmental Protection Agency, require skin sensitisation assessments for substances such as agrochemicals, biocides, industrial chemicals, cosmetics, and many pharmaceuticals.

The new skin sensitisation assessment scheme (TG 497) allows skin sensitisation potency to be assessed using an integrated testing strategy that combines several non-animal testing methods (in silico, in chemico, and in vitro). Before the official publication of TG 497, the skin sensitisation potency of various chemical substances was tested using animals, more recently in tests like the murine local lymph node assay (LLNA). By helping reduce the use of animals in testing, TG 497 fulfills part of the Three Rs (3Rs) — replace, reduce, refine — a framework used by many regulatory institutions worldwide for more targeted, humane, and ethical animal research.

The TG 497 defined approaches (DAs) provide other advantages over traditional testing as well. Extrapolating skin sensitisation data from LLNA to humans can be less accurate than the DAs in TG 497. According to the OECD, the DAs in TG 497 "have shown to either provide the same level of information or be more informative than the murine Local Lymph Node Assay (LLNA; OECD TG 429) for hazard identification (i.e. sensitiser versus non-sensitiser). In addition, two of the DAs provide information for sensitisation potency categorisation that is equivalent to the potency categorisation information provided by the LLNA."

Furthermore, all of TG 497's non-animal methods (in silico, in chemico, and in vitro) are faster and often cheaper than traditional toxicity testing methods. In silico predictions allow substances that cannot easily be synthesized/isolated (e.g., metabolites and impurities) to be evaluated, while in chemico and in vitro tests enable smaller amounts of a substance to be tested.

How Exponent Can Help

Exponent can support all stages of OECD TG 497 assessments. Our in silico toxicology group has extensive knowledge of in silico tools, including Derek Nexus and the OECD QSAR Toolbox. We can generate the expert assessment required for all in silico predictions used in regulatory submissions. Our wealth of experience validating models ensures that all in silico predictions are reliable, in accordance with OECD Principles of (Q)SAR Validation. In addition, our toxicology team can assist with strategy around identifying the appropriate in chemico/in vitro tests to complete the defined approach and provide expert study monitoring and data interpretation of the tests themselves.