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

MERCURY 134
2. HEALTH EFFECTS
crossing after exposure to both chemicals, but only methylmercury caused substantial cerebellar damage
(Magos et al. 1985). Additional changes in rats exposed to methylmercury have also been observed. Rats
exposed to a single gavage dose of 19.9 mg Hg/kg as methylmercuric chloride were found to have
statistically significant differences in open-field tests, such as decreases in standing upright, area traversed,
and activity, compared to controls. However, no accompanying histopathological changes were observed
(Post et al. 1973). The exposed animals were also lethargic and ataxic initially, but symptoms disappeared
within 2–3 hours. Changes in the phases of sleep were also observed in rats given 2 doses of 4 mg
Hg/kg/day as methylmercuric chloride (Arito and Takahashi 1991). Paradoxical sleep was decreased and
slow-wave sleep was increased. At a higher dose (12 mg Hg/kg/day for 2 days), circadian sleep patterns
were also disrupted. Administration of a single dose of methylmercuric chloride (0.8 mg Hg/kg) produced
blood-brain barrier dysfunction in rats (Chang and Hartmann 1972b) similar to that reported for inorganic
mercury as discussed previously. In rabbits given 5.5 mg Hg/kg as methylmercuric acetate for 1–4 days,
widespread neuronal degenerative changes (in cervical ganglion cells, cerebellum, and cerebral cortex) have
been observed without accompanying behavioral changes (Jacobs et al. 1977).
Longer-duration studies in animals have shown qualitatively similar effects, but generally at lower daily
doses with increasing durations of exposure. Rats given a dose of 10 mg Hg/kg as methylmercuric chloride
once every 3 days for 15 days showed degeneration in the cerebellum with flailing and hind leg crossing
(Leyshon and Morgan 1991). Rats given a TWA dose of 2.1 mg Hg/kg/day as methylmercury iodide or
2.4 mg Hg/kg/day as methylmercury nitrate by oral gavage for 29 days became weak and severely ataxic
and developed paralysis of the hind legs (Hunter et al. 1940). Severe degeneration of peripheral nerves,
posterior spinal roots, and trigeminal nerves were reported. Severe degenerative changes were also
observed in the dorsal root fibers of rats given 1.6 mg Hg/kg/day as methylmercuric chloride for 8 weeks
(Yip and Chang 1981). Similarly, ataxia (beginning the second week of exposure) and cerebellar edema
and necrosis occurred in rats after 7 weeks of exposure by gavage to 1.68 mg Hg/kg as methylmercury
dicyanidiamide for 5 days a week (Magos and Butler 1972). When rats were administered
0.8 mg Hg/kg/day as methylmercuric chloride by gavage for up to 11 weeks, effects similar to those
reported for mercuric chloride (e.g., neuronal degeneration of the cerebellum and dorsal root ganglia and
neurotoxic clinical signs) were seen but with increased severity (Chang and Hartmann 1972a).
Mice have shown comparable effects at similar doses. Mice exposed to 1.9 or 9.5 mg Hg/kg/day as methylmercury
in the drinking water for 28 weeks exhibited degeneration of Purkinje cells and loss of granular
cells in the cerebellum (MacDonald and Harbison 1977). At the higher of these doses, hind limb