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Objective: neurotoxicity of prenatal exposure to high concentrations of mercury (Hg) is well known; however, the doseresponse relationship at low exposure levels has not been quantified yet. This article illustrates the measurement of prenatal exposure to Hg and the pathway of exposure through the diet in Friuli Venezia Giulia, Italy., Design: description of a prospective cohort at the baseline., Setting and Participants: 242 mother- infant pairs living in Friuli Venezia Giulia were enrolled between 1999 and 2001., Main Outcome Measures: We measured the concentrations of Hg in the hair of mothers and children and of Hg and selenium (Se) in breast milk. The diet during pregnancy was estimated through a food frequency questionnaire (FFQ) with a detailed section regarding fish. We calculated the correlations between Hg and Se in the biological samples and estimated the association between Hg concentrations and fish consumption., Results: in general, Hg levels in hair and milk were positively associated with the consumption of fish from the lagoon of Grado and Marano. However, they were low in comparison with those of other fish-eating populations and below theWHO alert limits, likely because of the small consumption of fish among pregnant women, estimated from the FFQ. The concentration of Se in milk was also smaller than that reported in other international studies., Conclusion: in Friuli Venezia Giulia, fetal and perinatal Hg exposure is low. The children of the cohort will be followed- up at school age to measure possible neurodevelopmental effects of such low exposures to Hg.

The BMD approach has been used to compare the cell viability (MTT assay) of different rat (C6 and PC12, glial and neuronal, respectively) and human cell lines (D384 and SK-N-MC, glial and neuronal, respectively) after 24-h exposure to the following neurotoxic substances: Manganese Chloride (MnCl2), Methyl-mercury (Me-Hg) and the enantiomers of Styrene Oxide (SO). For all rat and human cell lines, the potency of the examined compounds was: MnCl2 < S-SO < R-SO < Me-Hg. A preliminary comparison with in vivo toxicity data for these substances gave rise to consistent results. Whereas a reasonable agreement between in vitro and in vivo data has been found for Mn and styrene oxide, a wide scatter of LOAEL has been reported for Me-Hg and these appear to be either much higher or lower than the BMD for the MTT assay we observed in vitro.

Background: In adults, MeHg poisoning is characterized by damage to discrete anatomical areas of the brain (visual cortex, loss of neurons from the granule layer of the cerebellum). However, the immature central nervous system (CNS), which is extremely sensitive to MeHg neurotoxicity, shows a diffuse and widespread damage disorganization of cerebral cortex cytoarchitecture, disappearance of granule cells with narrowing of the molecular layer. While adverse effects have been unequivocally demonstrated in poisoning incidents in humans (visual abnormalities, sensory impairment of the extremities, cerebellar ataxia, hearing loss, muscle weakness, tremor and mental deterioration), the implications of lower level exposures, such as those occurring in fish-eating populations, are still controversial. The high affinity of MeHg for thiol groups makes proteins and peptides bearing cysteines the predominant targets for structural and functional modification by MeHg in all subcellular compartments., Methods: The identification of MeHg cellular and sub-cellular targets in the CNS is complicated by the fact that it is difficult to observe the outcomes directly in vivo. In neurobiology, in vitro cell culture techniques have been successfully developed and employed to address specific questions of cell biology and nervous system functioning and provide a means to systematically study the complexity of cellular functions of the CNS elements. Moreover, they provide a convenient experimental tool for testing possible functions or postulates in vivo that otherwise might not be conducted., Results: Several mechanisms have been proposed as being implicated in the neurotoxic effects of MeHg. Examples of MeHg molecular effects which may be relevant to risk assessment are presented, including cell death mode, effects on microtubules, calcium signalling, oxidative stress, effects on neurotransmitter systems., Conclusions: Molecular and cellular approaches permit exploration of early biological responses to chemical or physical agents and definition of the role of these early effects in altered cellular structure and function.

Objectives: The present study was aimed at investigating early markers of renal damage and dysfunction in subjects exposed to low doses of mercury from different sources. Different groups of subjects were examined with urinary Hg excretion (HgU) ranging from 0.1 to 35.0 micrograms/g creatinine: 122 occupationally exposed workers, 22 subjects living in a non-polluted area, but consuming large amounts of tuna and sword fish, and 197 controls., Methods: Several markers of renal changes were measured in urine (albumin, fibronectin, beta 2-microglobulin, retinol-binding protein, tubular antigens, N-acetyl-beta-D-glucosaminidase activity) and serum (beta 2-microglobulin and cystatin C). Serum autoantibodies towards collagen, laminin and tubular antigens were assessed in subjects with abnormal renal markers. The role of glutathione-S-tranferases GSTT1 and GSTM1 polymorphisms in the inter-individual variability of biological response to Hg was also investigated., Results: Renal markers were not correlated with HgU. None of such markers differed significantly between exposed workers and controls, except for urinary beta 2-microglobulin, which was decreased in Hg-exposed workers (GM = 55.8 vs 86.6 micrograms/g creatinine), in the absence of any changes in serum concentration. Subjects usually eating tuna and sword fish showed an increased urinary excretion of beta 2-microglobulin, albumin and fibronectin. Serum titres of auto-antibodies did not differ between the groups. Neither in controls nor in exposed workers were the observed differences modified by the GSTM1 and GSTT1 genotypes., Conclusion: The present study did not provide evidence of any changes in kidney integrity and function in subjects exposed to very low levels of inorganic Hg resulting in urinary Hg lower than 35 micrograms/g creatinine. Nor did we obtain evidence of Hg-induced autoimmunity towards kidney components. The potential modifying role of GST polymorphisms could not be clarified in the absence of effects associated with exposure to the risk factor, i.e., to inorganic Hg. Preliminary data suggesting nephrotoxic effects of organic Hg from a diet rich in large fish resulting in increased levels of both blood and urinary Hg--which however did not exceed 20 micrograms/g creatinine--deserves further investigation.