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Biological networks – the key to a better understanding of chemical neurotoxicity

Schematic of an AOP network
Schematic of an AOP network
Dec 19 2019

Studying the effects of chemicals on the brain provides the basis for reducing disorders of learning and memory in children, as well as cognitive disorders in adults, such as Alzheimer’s and Parkinson’s. 

In the fight against these diseases, JRC scientists are involved in multiple collaborative projects aimed at better assessing the possible effects of chemicals on the nervous system.

Early life exposures to certain chemicals, such as pesticides, may have long-term adverse health consequences for the adult brain. 

In addition, aging and neurodegenerative diseases such as Alzheimer’s and Parkinson’s pose major challenges for societies. 

Animal models are limited. Relevant and reliable non-animal approaches, such as cell-based (in vitro) methods and computational (in silico) models, provide a promising means of mechanistic understanding the chemical contribution to these complex disease.

Challenge

A special issue of Toxicology and Applied Pharmacology, co-authored by a JRC scientist, describes a range of non-animal methods for assessing the potential of chemicals to cause developmental neurotoxicity (DNT).

Biological processes underlying neurotoxicity are complex. It is unlikely though that any of these alternative methods will provide a standalone solution for DNT testing. A similar challenge applies to the assessment of chemical neurotoxicity in adults. 

It is therefore necessary to develop solutions, called Integrated Approaches to Testing and Assessment (IATA), based on the combined use of multiple non-animal methods.

One way of guiding the optimal design of IATA for neurotoxicity is to leverage existing knowledge on Adverse Outcome Pathways (AOPs) that describe how chemical perturbations at the molecular level may cause a series of cascading events that ultimately result in neurotoxicity. 

Collaboration

In a collaboration with Liverpool John Moores University, JRC scientists have combined existing AOPs to form an AOP network for human neurotoxicity. The study illustrates how established concepts from network science can be used to identify the most common key events underlying neurotoxicity. Non-animal methods that model these pathways are therefore expected to be the most informative and useful in chemical safety assessment. 

The work was carried out in the context of the in3 project, an EU-funded Innovative Training Network of early stage researchers developing in vitro and in silico tools for chemical safety assessment.

Recommended reading

•    Alternative Approaches to Developmental Neurotoxicity Evaluation.  Toxicology and Applied Pharmacology
•    Development and analysis of an adverse outcome pathway network for human neurotoxicity