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Adverse effects on the central nervous system


The nervous system can be affected by exposure to numerous chemicals which have the ability to induce neurotoxic effects in humans. While acute effects are often reversible, the growing burden of neurodegenerative disease in the elderly has raised concerns over the possible contribution of chemicals, pesticides and other environmental contaminants to such diseases. The SCAHT research programme has a focus on neurotoxicology which reflects the growing public health importance of this research area.

Neurotoxicity can result from exposure to substances used in chemotherapy, radiation treatment, drug therapies, and organ transplants, as well as exposure to heavy metals such as lead and mercury, certain foods and food additives, pesticides, industrial and/or cleaning solvents, cosmetics, and some naturally occurring substances. Due to the nervous system's compensatory and adaptive mechanisms, there is a need to discriminate changes that are adverse (e.g. toxicologically relevant and predictive of the adverse outcome) from those that are adaptive (e.g. related to compensatory processes that do not lead to an adverse outcome).

The 2021 – 2024 SCAHT research programme supports a core project assessing the neurotoxicity of widely used industrial solvents using a variety of in vitro models and human studies.

[1] L. G. Costa, “Neurotoxicity testing: a discussion of in vitro alternatives,” Environmental Health Perspectives, vol. 106, supplement 2, pp. 505–510, 1998.

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P4 – Building a strategy to assess the neurotoxicity of solvents


Environmental and occupational exposure to chemicals may contribute to the development of several neurological diseases, including peripheral neuropathy, encephalopathy, motor neuron diseases and neurodegenerative diseases. In particular, organic solvents used in industries such as car repair, painting, furniture manufacturing, printing and cleaning have been associated with the development of several central nervous system (CNS) conditions, in particular with mild to severe toxic encephalopathy and in some cases with neurodegenerative diseases. The neurotoxicity of these solvents is, unfortunately, in most cases not assessed prior to placing them on the market. To efficiently protect the population and in particular the workers who are generally greatly exposed it is important to determine safe air concentrations for solvents to which they can be exposed.

Currently, the neurotoxicity or developmental neurotoxicity of a chemical is specifically evaluated only when a trigger has been found in single dose (OECD Test Guidelines, rarely applied) or repeated dose toxicity studies. The recognised methods for the evaluation of the neurotoxic potential of chemicals are complex in vivo tests in rodents, which are very laborious, expensive, and difficult to apply in a standardised manner, thus resulting in limited reproducibility of results.

The ultimate aim of this project is to provide safe air concentrations of solvents that will not likely produce neurotoxicity in exposed individuals by using a combination of in vivo (zebrafish embryo), in vitro and in silico tools, coupled with controlled in vivo human exposure experiments. This project will also provide insight in the mechanisms of neurotoxicity of the solvents and provide data needed for the development of Adverse Outcome Pathways (AOPs) being useful for risk assessment and regulatory purposes. 

Project lead

Dr Marie-Gabrielle Zurich
Marie-Gabrielle.ZurichFontanellaz@unil.ch

University of Lausanne, Department of Physiology, Glial cells metabolism and neurotoxicity

Publications

Human IPSC-Derived Model to Study Myelin Disruption

International Journal of Molecular Sciences , 31 Aoû 2021


Human Oligodendrocytes and Myelin In Vitro to Evaluate Developmental Neurotoxicity

International Journal of Molecular Sciences , 25 Jul 2021


Neuroinflammatory Response to TNFα and IL1β Cytokines Is Accompanied by an Increase in Glycolysis in Human Astrocytes In Vitro

International Journal of Molecular Sciences , 14 Avr 2021