Exposure to environmental chemicals in the period of rapid growth of brain during first years of life may lead to cognitive problems, learning, memory and motor dysfunctions, which are increasing worldwide. At low doses of exposures, sub-clinical decrements are more common than neurodevelopmental disorders, but epidemiological evidence is contradictory. Consequently, for many substances of concern there is a lack of consensus on threshold levels below which no adverse effects are observed. Re-evaluation of existing thresholds is needed, considering the main sources of uncertainty and integrating main factors of susceptibility (genetic background, nutrition, sex). Moreover, critical endpoints used in re-evaluation of exposure-effect relationships need to be based on the mechanistical knowledge that can be obtained by the use of appropriate effect biomarkers. The main study objective is to provide an improved assessment of exposure-effect associations for selected potentially neurotoxic compounds in the existing Slovenian birth cohorts, considering abovementioned susceptibility factors. This will be done by 1) integration of genetic variability data into the physiologically based pharmacokinetic models, 2) probabilistic exposure assessment and 3) implementation of early biological response markers. These are key steps toward an improved health risk assessment which is still lacking or is inconsistent for a number of environmental chemicals. The aim of the proposed project will be achieved by bringing together expertise from the fields of human biomonitoring, medical physics and computational science. This will strengthen the research field of environmental health and initiate a sustainable cooperation between the disciplines. The joint collaboration will be initiated by setting up a computational framework for prenatal mercury exposure, for which the most extensive data is available and will continue to predict low-dose chronic (life-time) mixtures effects.

RSF START