Tissues from dams, fetuses, and neonates shall be collected from animals exposed in range-finding studies, and analyzed for Hg by atomic absorption spectroscopy. Mercury concentrations will be measured in blood of the dam, fetus and neonate during gestation and at various times postpartum. The study design will be finalized after the initial planning meeting to determine data gaps, and after initial pilot studies. The rat PBPK Hg model can be converted into a human model by adjusting the compartment volumes and flow rates. The molecular mechanisms of this disease process are largely unknown.
Lung fibrosis is characterized by fibroblast hyperplasia.
Particles that are well-known to induce fibrosis include chrysotile asbestos and silica. Recent attention has focused on industrial emission-source fly ash particles that are rich in metals such as vanadium and nickel. Furthermore, bacterial endotoxin induce PDGF-R a expression and this may be significant since many ambient pollution particles are associated with surface adhered endotoxins. Thus, fibrogenic particles that cause pulmonary fibrosis activate the fibroblast PDGF receptor system and this results in an enhanced proliferative potential of lung fibroblasts. That inorganic particles interfere with regulatory mechanisms that normally control the biological activity of PDGF during tissue repair and maintenance was postulated.