The analytical framework for environmental sampling has been applied in the assessment of wild fish and seafood contribution to dietary exposure to persistent pollutants. In addition, air toxicants have been identified in various ambient and indoor environments. In terms of modelling environmental exposure, assessment of BPA, PM and PAHs has been carried out, as well as a comprehensive assessment of Hg exposure through the food chain.
With regard to human biomonitoring, analysis of organochlorine compounds and metals in biological samples (blood, brain, milk) in venous serum of pregnant mothers from Arctic areas, farmworkers exposure to pesticides in Spain, phthalates and DINCH metabolites, bisphenols, parabens, and triclosan in Slovenian populations, and metals in from population samples from the PHIME study has been carried out. Information from environmental exposure and personal sensors, as well as from Agent Based models data has been used to estimate personal exposure and validate it against HBM data.
Biological samples collected within the PHIME (overall 1002 individuals from Italy, Slovenia and Croatia) have been subjected to genome profile analysis, for assessing the polygenic risk scores. With regard to other omics analysis, metabolomics analysis has been concluded in the subjects of the PHIME cohort study, in both plasma and urine samples from mothers and children respectively, as well as from the Spain-EXHES cohort.
To mimic exposure to environmentally relevant exposure to neurotoxicants during neurodevelopment, SH-SY5Y cells (neuroblastoma cell line) were exposed to an environmentally representative mixture of 8 pollutants. Several cellular and molecular outcomes have been assessed, including cell metabolic activity, death and apoptosis, followed by transcriptome and immunocytochemical analysis.
The concentrations used to expose SH-SY5Y cells were based on the expected concentrations of each pollutant in the human brain calculated by PBPK modelling developed. More detailed toxicokinetic interactions regarding the blood-brain-barrier have been investigated in vitro. The generic PBBK model has been parameterized using literature as well as QSAR delivered parameterization data for phthalates, bisphenols, PFOS-PFOA and metals, while toxicokinetic interactions of the BPA, BPF and BPS tertiary mixture, as well as the DEHP, BBzP, DINP and DNBP quaternary mixture have been quantified.
Bioinformatics analysis from in vitro samples revealed the dysfunctions by identifying the disturbances in metabolic pathways than can lead to the development of reactive oxygen species inside cells, as well as the energy metabolism dysfunction. The omics analysis of the human samples into metabolic pathways, using bioinformatics. The key finding is that maternal exposure to phthalates and metals may affect child neuro development mainly through perturbations in the metabolism of citric acid (TCA cycle), urea cycle, and amino acid metabolism with possible disruption of mitochondrial oxidative phosphorylation.
EWAS analysis from the cohort studies revealed that different factors have positive and negative contributions, while the importance of dietary factors on child neurodevelopment, as well as the impact of social factors. It was also found that the imbalance between the cellular reactive oxygen species, which may be an effect of exposure to metals, and the inability of the cell to detoxify them, leads to oxidative stress.
