Various recent epidemiological studies indicate that low-dose chemical exposure during brain development can have adverse effects on cognitive development in childhood. The aim of this project is to evaluate and develop screening methods for chemical-induced developmental neurotoxicity and to improve assessment of exposures and effects. Hazard characterization for developmental neurotoxicity by chemicals and low-dose mixtures using newly developed experimental approaches will be combined with the study of associations between neurodevelopment and exposure to these chemicals in large EU epidemiological cohorts. There is particular attention for the exposure to environmental pollutants and possible neurotoxic effects at low doses and in mixtures. The Neurotoxicology Research Group at IRAS will focus on the effects of single chemicals and mixtures in in vitro screening tools for developmental neurotoxicity. The Epidemiology Division at IRAS contributes to project-wide (cohort) data analysis procedures.

For published or accepted papers of the DENAMIC project look under Publications.

The developed methods and obtained results will give recommendations for risk management to the EU and WHO and will largely support the EU chemicals legislation for identifying (potential) neurotoxicants.

The objectives of the DENAMIC project are:

  • to develop a toolbox of assays to screen chemicals for (developmental) neurotoxicity
  • to improve understanding of mechanisms on the interaction between low doses of (mixtures) and (developmental) neurotoxicity
  • to generate exposure data of mothers and children to (mixtures of) neurotoxic compounds
  • to contribute to understanding potential associations between exposure to low-dose chemical mixtures and developmental neurotoxicity in children

Publications:

  1. Meijer M, Hendriks HS, Heusinkveld HJ, Langeveld WT, Westerink RH. 2014. Comparison of plate reader-based methods with fluorescence microscopy for measurements of intracellular calcium levels for the assessment of in vitro neurotoxicity. Neurotoxicology 45:31-37.
  2. Meijer M, Dingemans MM, van den Berg M, Westerink RH. 2014. Inhibition of voltage-gated calcium channels as common mode of action for (mixtures of) distinct classes of insecticides. Toxicological Sciences 141(1):103-111.
  3. Meijer M, Hamers T, Westerink RH. 2014. Acute disturbance of calcium homeostasis in PC12 cells as a novel mechanism of action for (sub)micromolar concentrations of organophosphate insecticides. Neurotoxicology 43:110-116.
  4. de Groot MW, Dingemans MM, Rus KH, de Groot A, Westerink RH. 2014. Characterization of calcium responses and electrical activity in differentiating mouse neural progenitor cells in vitro. Toxicological Sciences 137(2):428-435.
  5. de Groot MW, Westerink RH, Dingemans MM. 2013. Don't judge a neuron only by its cover: neuronal function in in vitro developmental neurotoxicity testing. Toxicological Sciences 132(1):1-7.