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NHR DEVTOX — Result In Brief

Project ID: 512153
Country: Belgium

Towards animal-free testing of toxic chemicals

There is increasing concern regarding chemicals in the environment that are causing adverse effects in the reproductive system. New methods of assessment for so-called endocrine disruptors (EDs) are needed to replace current animal-based procedures.
Towards animal-free testing of toxic chemicals
Toxicity data is required for chemicals that are produced in quantities of more than 1,000 tonnes per year. Currently accepted methods to obtain this information use animals in the main and are also costly. Furthermore, animal models may not always be able to predict toxicity effects in the human system.

The NHR Devtox project aimed to investigate the use of nuclear hormone receptors (NHRs) for tests on developmental toxicity as an alternative to experimental animals. NHRs are activated proteins that bind to a specific DNA sequence thereby controlling, in some cases, regulation of reproductive tissues.

NHR Devtox scientists were aware that signalling pathways for NHR are highly conserved between species. This similarity meant that effects of EDs on NHRs as tested in the lab could be used to determine potential hazards to humans.

The project consortium successfully developed a protocol to investigate the effects of toxic environmental chemicals on male reproductive system development. Genomic and proteomic techniques included identification of relevant NHRs and generation of cell lines with NHR reporter genes that indicate when a gene has been expressed by an easily identifiable marker.

Project scientists recommended that future areas for research should be determined based on the most important clinical effects. One possible approach was to investigate data on developmental abnormalities that were linked to hormones.

Outcomes of the project have shown that NHR technology constitutes a promising basis for in vitro assays relevant to developmental toxicology. Innovative protocols developed will be able to form a platform for the development of new approaches to find out the toxicological effects of EDs.

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