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ACROPOLIS: Mixtures of pesticides

 

Principle investigator: Harm J. Heusinkveld, M.Sc.
 
Project leader: R.H.S. Westerink, Ph.D.
 
Project description:
 
The aim of the EU-funded ACROPOLIS project is to develop new toxicological approaches for identifying possible additive or synergistic neurotoxic effects and to develop a strategy for refinement of cumulative assessment groups for risk assessment purposes.
 
Methods:
The cytotoxicity of certain low-dose mixtures of pesticides will be assessed in different cell lines. Effects of a selection of these compounds and mixtures on activation and/or inhibition of postsynaptic neurotransmitter receptors and presynaptic neurotransmitter release mechanisms will be investigated. Fluorescent intracellular calcium imaging techniques will be combined with measurements of neurotransmitter secretion to assess the mechanisms of toxicity.
 
Background:
A pesticide is a compound or mixture of compounds used to kill or repel unwanted species like insects, moulds, rodents or plants. Although there are benefits to the use of pesticides, some are able to exert unwanted toxic effects on plants, animals or humans. Pesticides belong to the group of most abundant environmental toxicants of which some are persistent. Due to their abundance, persistence and widespread use, humans are inevitably exposed to these compounds in various ways and at all life stages, including vulnerable developmental stages. (Neuro)toxicity data is for most compounds lacking. Current risk assessment is largely bases on single compounds, whereas human pesticide exposure usually involves low-dose exposure to complex mixtures of several pesticides. It is therefore essential to include mixture effects in current risk assessment strategies
 
Publications:
- Meijer M., Hendriks H.S., Heusinkveld H.J., Langeveld W.T., Westerink R.H.S. (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.
- Heusinkveld H.J., Molendijk J., van den Berg M., Westerink R.H.S. (2013). Azole fungicides disturb intracellular Ca2+ in an additive manner in dopaminergic PC12 cells. Toxicological Sciences 134, 374-381.
- Heusinkveld H.J., Westerink R.H.S. (2012). The organochlorine insecticides lindane, dieldrin and their binary mixture disturb calcium homeostasis in dopaminergic PC12 cells. Environmental Science & Technology 46, 1842-1848.
- Heusinkveld H.J., Westerink R.H.S. (2011). Caveats and limitations of plate reader-based high throughput kinetic measurements of intracellular calcium levels. Toxicology and Applied Pharmacology 255, 1-8.
- Heusinkveld, H.J., Thomas, G.O., Lamot, I., van den Berg, M., Kroese, A.B.A., & Westerink, R.H.S. (2010). Dual actions of lindane (γ-hexachlorocyclohexane) on calcium homeostasis and exocytosis in rat PC12 cells. Toxicology and Applied Pharmacology  248, 12-19.
- Dingemans, M.M.L., Heusinkveld, H.J., van den Berg, M., Bergman, A., Westerink, R.H.S. (2010). Bromination pattern of hydroxylated metabolites of BDE-47 affects their potency to release calcium from intracellular stores in PC12 cells. Environmental Health Perspectives 118, 519-525. 
- Dingemans, M.M.L., Heusinkveld, H.J., de Groot, A., Bergman, A., van den Berg, M., Westerink, R.H.S. (2009). Hexabromocyclododecane inhibits depolarization-induced increase in intracellular calcium levels and neurotransmitter release in PC12 cells. Toxicological Sciences 107, 490-497.