How dangerous are different chemicals for the nervous system of fetuses and young children? In order to test this, complex and expensive animal experiments were previously necessary. But now researchers have developed a battery of tests that can be used to test large numbers of chemicals without any animal testing. Cultures of human cells form the basis. Tests have shown that these cell cultures are on par with animal testing for most chemicals. They could therefore replace animal experiments in the future.
Our nervous system is highly complex and takes several years to fully develop. This begins in the womb and continues throughout the first years of life. However, this complex process is prone to failure, especially when we are exposed to environmental toxins such as metals, pesticides and pharmaceuticals. The result can be permanent developmental disorders in the developing child. So far, however, the potential for developmental neurotoxicity is not even known for 200 substances. The reason: Previous methods were based on animal experiments, which cost them one million euros per substance tested.
A test battery as an alternative to animal testing
Researchers led by Jonathan Blum from the University of Konstanz have therefore been looking for a more cost-effective and ethically acceptable method to be able to test significantly more substances for their potential danger. To do this, they assessed various existing alternative methods to classic animal experiments and combined ten of them in a large-scale test battery. The selected tests are all carried out in test tubes and not on living organisms. Cell cultures of human cells are used, which are exposed to different substances at different stages of their development, for example after 72 or 120 hours.
The test battery has several advantages compared to animal experiments: It is not only more affordable, but can also test significantly more substances for their toxicity than would be possible in animal experiments in the same period of time. In addition, the tests may even provide more reliable results because they work with human cells from the start. "In the ideal case, this increases the validity of the test procedures compared to animal experiments, since the respective results do not have to be transferred or extended from an animal model, such as mice or rats, to the processes relevant to humans," explains Blum's colleague Ellen Fritsche.
Using the test battery, the scientists screened a total of 120 chemical substances and selected them from as broad a range as possible: “These included some substances that are known to be toxic to the nervous system, such as certain pesticides or flame retardants. However, substances considered harmless were also included as negative controls,” says Fritsche.
Numerous application possibilities conceivable
The result: The test battery based on the cell cultures identified most of the toxins already known as such (24 out of 28) as dangerous and thus has an accuracy of 82 percent. According to the research team, this makes it equal to animal experiments. In addition, the battery did not alarm for any of the negative controls. This means that she did not mistakenly classify harmless substances as toxic. According to Blum and his colleagues, these results are promising and could - after a little more fine-tuning - qualify the test battery for large-scale use.
The developers of these cell-based tests are already in contact with the European Commission and the US Environmental Protection Agency. According to the researchers, in the future the test battery could, among other things, provide hazard data for pesticides that are to be approved in the EU. Or screen substances that occur in the living and working environment and have not yet been adequately tested for their developmental neurotoxicity. In any case, the test battery has the potential to completely replace previous animal-based methods for testing potentially neurotoxic chemicals, according to the scientists.
Source: University of Konstanz; Specialist article: Chemosphere, doi: 10.1016/j.chemosphere.2022.137035