revised final - Agency for Toxic Substances and Disease Registry ...

MERCURY 131
2. HEALTH EFFECTS
any exposure group. The methylmercury-treated monkeys (all groups) appeared normal in terms of cage
behavior throughout the entire exposure period, supporting the conclusion that there was no significant loss
in the neuron population. Examination of tissue samples did not reveal any apparent degradation in the
structure of neurons or chronic changes in the glial cells (e.g., the appearance of hypertrophic astrocytes),
which are commonly observed following exposure to high levels of mercury. No apparent dilation of the
perivascular spaces was observed. The average volume of the cortex of the calcarine sulcus did not differ
significantly from controls for any methylmercury-treated group. The methylmercury-clearance group had
low levels of methylmercury present in tissues; however, the level of inorganic mercury was also elevated.
The astrocytes and microglia in the methylmercury group contained the largest deposits of inorganic
mercury. Comparing the results of the methylmercury and inorganic mercury groups suggests that
inorganic mercury may be responsible for the increase in reactive glia (Charleston et al. 1994).
Charleston et al. (1996) studied the effects of long-term subclinical exposure to methylmercury on the
number of neurons, oligodendrocytes, astrocytes, microglia, endothelial cells and pericytes within the
thalamus from the left side of the brain of the monkey Macaca fascicularis. These parameters were
determined by use of the Optical Volume Fractionator stereological method. The accumulated burden of
inorganic mercury (IHg) within these same cell types has been determined by autometallographic methods.
Four groups of female monkeys (n=4-5) were exposed to 50 µg Hg/kg/day methylmercury in apple juice for
6, 12, or 18 months, or 12 months followed by 6 months without exposure (clearance group). One control
animal each was sacrificed with the 6- and 12-month exposure groups, and two additional animals were
sacrificed at the end of the experiment. All monkeys appeared normal—no changes in behavior or motor
skills were observed. Hematological function (white blood cell count and differentiation, erythrocyte count,
hemoglobin, hematocrit, and red cell indices) and blood chemistry (urea nitrogen, creatine, bilirubin,
albumin, total protein, alkaline phosphatase, and electrolytes) were normal. No weight loss was observed.
Neurons, oligodendrocytes, endothelia, and pericytes did not show a significant change in cell number for
any exposure group. Astrocyte cell number exhibited a significant decline for both the 6-month (44.6%)
and clearance exposure groups (37.2%); decreased astrocyte counts were also observed in the other
exposure groups, but these were not significant. The microglia, in contrast, showed a significant increase in
the 18-month (228%) and clearance exposure groups (162%). Results from mercury speciation and
quantification analysis of contralateral matched samples from the thalamus of the right side of the brain
from these same monkeys indicated that methylmercury concentrations plateaued at around 12 months
exposure, whereas the inorganic levels, presumably derived from demethylation of methylmercury,
continued to increase throughout all exposure durations. Autometallographic determination of the