Impact of neurotoxins on the immature brain
The presence of neurotoxic substances in food is not only worrying to the individual consuming the food but to developing foetuses in utero and exposure via breast milk to the child. The developing nervous system is particularly sensitive to the effects of neurotoxins. The EU-funded project Devnertox aimed to determine the mechanism of action of persistent pollutants like methylmercury (MeHg) and polychlorinated biphenyls (PCBs). In addition, there is little information on synergistic effects of one or more of the toxins. Risk assessment and neurotoxicity studies are difficult to analyse due to the complexity of the nervous system and multiple effects of exposure also create additional problems. Devnertox scientists therefore focused on generating improved experimental models to study the effects of MeHg and two PCBs, one non-dioxin like and one dioxin-like, to overcome these limitations. Neural stem cells were studied in vitro to overcome complexities inherent in nerve cells. Moreover, neural cells exposed to toxins can undergo different types of cell death and there may be cross-talk between the various death pathways. For in vivo studies, analysis of behaviour was selected to detect subtle modifications and to study the same animal at different stages of development. Learning and memory were both found to be impaired in both rats and mice and by multiple tests. Exposure to MeHg not only affects cognitive function but also motivation-driven behaviour. Neurological effects resulted from chemical, hormonal and behavioural changes, sometimes with species differences. The Devnertox project found that overall in vitro tests provided a relevant comparison against studies on experimental animals. The range of well characterised models used in the project provided a better assessment of potential neurotoxins. Outcomes from the results suggest that it is important to measure actual levels of the toxin in tissues and cells as levels in cells can vary depending on type. Devnertox also recommend a biomonitoring approach using validated relevant biomarkers to assess the risk of neurodevelopmental effects and the margin of exposure from food and other sources. Future studies suggested include the issue of combined or complex exposures. Moreover, they stress it would be valuable to create a framework where human and animal data can be integrated for a less costly assessment of the effects of multiple exposures to sub-threshold concentrations. Devnertox refined and improved the assessment of the effects of neurotoxins on the development of mammals. Furthermore, the project has provided a strategy to define guidelines for exposure limits, particularly in sensitive groups such as children.
