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.