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WP7.1: Improving in vitro/in vivo correlations – Neurotoxicology

 

WP7.1 results, download the entire summary: Image Results WP7.1.pdf

 

To examine responses for the nervous system in WP7.1, the first 26 ACuteTox reference chemicals (neurotoxic and non-neurotoxic) were studied  in native or differentiated human neuroblastoma SH-SY5Y cells, primary cultures of mouse or rat neurons, and mature re-aggregated rat brain cells by using around 40 different endpoints.

 

The results showed that the broad collect of assays could in a very good way predict the neurotoxic compounds. However, no general test are available that can identify all neurotoxic outliers.

 

The following end-points were identified as the best candidates for identification of neurotoxic compounds and were further evaluated and used in the second phase in which 33 additional reference chemicals were  tested:

 

  • Caspase-3 gene expression in primary cultures of cerebellar granule cells (P37)
  • Cell markers for neurons (NF-H) and astrocytes (GFAP) by measuring gene expression in reaggregate cultures (P20)
  • Acetylcholine esterase (AChE) activity in SH-SY5Y cells (P5)
  • GABAA receptor in primary cultures of cortical neurons (P13)
  • Cell membrane potential (CMP) in SH-SY5Y cells (P16)