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

MERCURY 150
2. HEALTH EFFECTS
low dose mercury affects thymocyte development and stimulates certain mitogen- or antigen-induced
lymphocyte activities in mice. The authors note that these results, in the context of other studies where
methylmercury was observed to have suppressive effects, suggests that methylmercury enhances immune
function within a narrow dose range. The blood levels of mercury in the present study are close to the
levels found in fish-eating populations. The authors note that the clinical relevance of slight stimulation of
some immune functions is unknown, but the induction of autoimmunity by methylmercury can not be
excluded.
Groups of guinea pigs exposed to a single dose of 11.5 mg Hg/kg as methylmercuric chloride at various
times during gestation (66–69 days) showed differences in the manifestation of developmental
neurotoxicity, depending on the period of development when exposure occurred (Inouye and Kajiwara
1988). Primarily developmental disturbances of the brain (e.g., smaller brains, dilated lateral ventricles,
reduced size of hippocampus and nucleus caudate-putamen) occurred with exposures at 3, 4, or 5 weeks of
pregnancy. Exposure during a later pregnancy stage (6 or 7 weeks) produced widespread focal
degeneration of neurons in the neocortical region of fetal brains. In hamsters, methylmercuric chloride
administered as a single dose of 8 mg on Gd 10 or of 1.6 mg Hg/kg/day on Gd 10–15 resulted in
degeneration of cerebellar neurons in neonates (Reuhl et al. 1981a). Examination of offspring
275–300 days after birth showed similar degeneration (Reuhl et al. 1981b). It was not reported whether
these histopathological changes correlated with behavioral changes.
Functional disturbances have also been observed following exposure to methylmercuric chloride during
gestation. A single dose of 16 mg Hg/kg as methylmercuric chloride administered on Gd 13, 14, 15, 16, or
17 resulted in decreased spontaneous locomotor activity at 5 weeks of age, decreased righting response,
abnormal tail position during walking, flexion, and crossing of the hindlimbs (Inouye et al. 1985).
Histopathological examination of these animals showed dilated lateral ventricles, decreased caudate
putamen, and a slightly simplified cerebellar pattern. Neonates in this study were cross-fostered within
24 hours after birth to prevent intake of mercury through the milk. The offspring of mice receiving 3, 5, or
10 mg Hg/kg/day as methylmercuric hydroxide on day 8 of gestation exhibited a decreased number of
avoidances, an increased number of escapes, and an increased trials to reach the criterion on a 2-way
avoidance task (Hughes and Annau 1976). No effects were present in the 2 mg Hg/kg dose group.
Offspring of rats exposed to 4 mg Hg/kg/day as methylmercuric chloride on Gd 6–9 showed impaired
swimming behavior, increased passiveness, and an increased startle response (Stoltenburg-Didinger and
Markwort 1990). At 0.4 mg Hg/kg/day, the offspring showed an increased startle response, but at 0.04 mg