The aim of this experiment is to determine the species of mercury compound(s) that are the proximate toxic form by comparing the levels of inorganic (Hg) and methylmercury (MeHg) in the primate brain with morphologic and morphometric changes. """"""""Clinically"""""""" subtoxic levels of pure CH3 HgOH and HgCl2 will be administered for 2 years and 3 months respectively and the blood and brain (8 sample sites) MeHg and inorganic levels will be determined. Special attention will be paid to assure the purity of the mercury compounds administered and quality control of the assay methods. These findings will be correlated with the type(s), time of onset, and location of morphologic lesions and morphometric measurements on three groups of cells -- neurons, glial cells and capillaries. When appropriate, measurements will include volumes and surfaces of cells, nuclei, nucleoli, Golgi Complexes, mitochondria, Nissl (RER), lipofuscin, pigment granules, lysosomes, phagosomes, surface area of plasma membranes (synapses and dendritic spines). To accomplish the above we have combined the primate experimental procedures, experience, facilities, and past research findings of the mercury research group at the University of Washington with the mercury analytical technology expertise and mercury metabolism knowledge of the Environmental Hygiene group at the Karolinska Institute in Sweden. This major effort is crucial to further the development of knowledge of the neurotoxic mechanisms of mercury, a major and increasingly important global environmental and occupational problem by providing data directly relevant to the human.
