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

MERCURY 132
2. HEALTH EFFECTS
distribution of IHg by cell type indicates that both the astrocytes and microglia contain substantially
elevated IHg deposits relative to all other cell types. The data suggest that the inorganic mercury present in
the brain, accumulating after long-term subclinical methylmercury exposure, may be a proximate toxic form
of mercury responsible for the changes within the astrocyte and microglial populations.
Rice (1996a) evaluated delayed neurotoxicity produced by methylmercury in monkeys treated with
methylmercury from birth to 7 years of age. When these monkeys reached 13 years of age, individuals
began exhibiting clumsiness not present previously. Further exploration revealed that treated monkeys
required more time to retrieve treats than did nonexposed monkeys and displayed abnormalities on a
clinical assessment of sense of touch in hands and feet, despite the fact that clinical examinations performed
routinely during the period of dosing had not yielded abnormal results. Another group of monkeys, dosed
from in utero to 4 years of age, also took longer to retrieve treats when assessed years after cessation of
exposure. These observations were pursued in both groups of monkeys by objective assessment of
somatosensory function in the hands: both groups of monkeys exhibited impaired vibration sensitivity. The
results suggest that a delayed neurotoxicity occurred when these monkeys reached middle age. The author
notes persons with Minamata disease also have symptoms of delayed neurotoxicity. The results from a
study of more than 1,100 Minamata patients over the age of 40 indicated a difficulty in performing daily
activities that increased as a function of age compared to matched controls. Methylmercury may represent
the only environmental toxicant for which there is good evidence for delayed neurotoxicity observable
many years after cessation of exposure.
Rice (1996b) further compares the sensory and cognitive effects of developmental methylmercury exposure
in monkeys to the effects in rodents. Developmental exposure to methylmercury in the Macaque monkey
produced impairment of function in the visual, auditory, and somatosensory systems. In addition, delayed
neurotoxicity was observed in monkeys years after cessation of dosing, manifested as overall clumsiness
and slowness in reaching for objects. The effects of developmental methylmercury exposure on cognitive
function in monkeys are more equivocal; both positive and negative results have been obtained, with no
obvious pattern with regard to possible domains of impairment. Prenatal methylmercury exposure in
rodents produced retarded development and impairment of motor function, while the evidence for cognitive
impairment is less consistent. Derivation of reference doses based on these data from monkeys and rodents
is remarkably congruent, and is virtually identical to values derived from evidence for developmental
impairment in humans. Research needs include determination of neurotoxic effects at lower body burdens