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Analytical Chemistry

First animal-free toxicity test emerges

BASF-Givaudan system for skin is ‘truly ground-breaking,’ animal rights group PETA says

by Alex Scott
June 30, 2021


A photo of a mouse in a person's gloved hands.
Credit: Shutterstock
The new three-test system is expected to eliminate the use of thousands of animals—including mice—for testing.

Marking a major development in the world of toxicology, the Organisation for Economic Cooperation and Development (OECD) has for the first time approved a toxicology test that does not rely on animals. The novel approach, developed by BASF and the Swiss fragrance firm Givaudan, uses three methods—instead of one test on an animal—to determine if a developmental product causes allergic reactions to the skin.

The development is “truly ground-breaking” says Julia Baines, UK science policy manager for People for the Ethical Treatment of Animals, an animal rights group. More than 47,000 animals were used for skin tests in Europe in 2017, she says, citing EU data. “These animals suffer from a variety of adverse effects such as swelling, blistering, and inflammation before they are killed and dissected,” she says.

Under mutual acceptance of data rules, all member countries of the OECD—including the UK, the US, and European Union member states—must accept the new approach for legally-required chemical toxicity tests, Baines says. “This means we can expect to see an immediate global shift away from using animals in skin sensitization tests.

Exposing animal skin to an allergen provokes a series of responses or “key events” collectively known as an adverse outcome pathway. BASF and Givaudan have mimicked these events in three separate non-animal tests.

The first of the tests evaluates the ability of a substance to bind to skin proteins. Instead of native skin proteins, synthetic heptapeptides are used as surrogates.

The second test determines whether a substance is allergenic by identifying whether a skin protein has been altered when bound to it. In an animal, these altered proteins are recognized by specialized immune cells in the skin known as dendritic cells. The second test measures how ex vivo dendritic cells change when incubated with a test substance.

The third test detects stress to skin cells by linking a cellular stress response pathway to a bioluminescence reporter gene sourced from the firefly enzyme luciferase. If the cells are stressed, they start to glow.

The three-test approach is even more accurate for human skin allergy risk than traditional animal testing, according to Andreas Natsch, head of in vitro molecular screening at Givaudan.

BASF is giving away all intellectual property associated with the tests, which it will deploy in-house on its developmental products. Partly as a result of expensive raw materials and equipment, the new tests will be more expensive than animal tests, says Robert Landsiedel, vice president of special toxicology for BASF.

BASF has been working towards this goal since 2008, Landsiedel says. The approach could be a blueprint for replacing other animal tests. However, non-animal tests for areas such as eye irritation or hormone system effects will require new technologies that could be decades away, he says.



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