A collaborative research team looked at improving toxicity testing via in vitro tests, to enable faster and more efficient evaluation of chemical effects on human health without the use of animals.
The study, published yesterday in Nature Communications, used high-speed, automated screening to test a library of ten thousand chemicals using cells and isolated molecular targets instead of laboratory animals. The work is part of the Tox21 (Toxicology in the 21st Century) programme, a collaboration between the National Institute of Health (NIH), the US Environmental Protection Agency (EPA) and the US Food and Drug Administration (FDA).
The Tox21 10K chemical library has been screened against a panel of 30 human cell-based assays, focused on nuclear receptor signalling and stress response pathways, to produce the largest set of high quality in vitro toxicity data known to date. The results, along with knowledge of chemical structure, were used to identify chemical structure–activity signatures and inform the development of models that predict in vivo toxicity end points. The models based on data from in vitro assays were distinctly better at predicting human toxicity end points than animal toxicity.
So far the results are encouraging but more work is needed to enable a shift towards non-animal approaches for safety assessment of chemicals for human health. This includes building awareness with regulatory agencies as well as expanding the focus of the studies beyond the two tested areas. In the continuation of the Tox21 programme, more assays will be included to cover additional pathways and targets that could be relevant for toxicity.
Full implementation of the envisioned paradigm shift in toxicity testing will require validation of the new approaches, a substantial effort which will take time. However, in the shorter-term there is potential to identify a battery of in vitro tests that can be used for prioritisation and selection of the chemicals, so that fewer compounds will undergo compulsory regulatory testing in animals. The availability of data from studies such as this will also support the development of adverse outcome pathways (AOPs), an area in which the NC3Rs currently has a programme of work.
There are also European initiatives working in this area, such as the newly launched EU-ToxRisk project, which aims to develop a mechanism-based, human relevant, non-animal approach to risk assessment that can replace regulatory repeat-dose systemic toxicity testing. The NC3Rs is one of the 39 partners and will play a role in facilitating regulatory engagement in the project. This will help to ensure the research is focused towards regulatory need and that there is ultimately acceptance of any new non-animal technologies developed.
Dr Fiona Sewell, Programme Manager in toxicology and regulatory sciences at the NC3Rs commented on the Nature study in an article published today in The Scientist.