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

MERCURY 135
2. HEALTH EFFECTS
paralysis was observed as early as 8 days, whereas at 1.9 mg Hg/kg/day, decreases in motor activity and
hind limb paralysis did not develop until 24 weeks of exposure. Interestingly, cerebellar lesions were
observed at 1.9 mg Hg/kg/day as early as 8 days after the start of dosing. Neuronal degeneration and
microgliosis were observed in the corpus striatum, cerebral cortex, thalamus, and hypothalamus,
accompanied by hind leg weakness, in mice administered 1 or 4 mg Hg/kg/day as methylmercuric chloride
by gavage for 60 days (Berthoud et al. 1976). Similarly, a marked neurotoxic disturbance (not further
identified) was reported in mice that received 3.1 mg Hg/kg/day as methylmercuric chloride in the diet for
26 weeks (Mitsumori et al. 1981). No effects of this type were observed in this study at 1.6 mg Hg/kg/day,
but it is unknown whether more subtle neurological effects may have been missed, as the intent of this study
was not to identify neurotoxic effects of methylmercury.
Some studies suggest that cats and monkeys are more sensitive to the neurotoxic effects of organic mercury
than rodents. Cats fed tuna contaminated with methylmercury at doses equivalent to 0.015 mg Hg/kg/day
for 11 months, starting when the cats were kittens, displayed degenerative changes in the cerebellum and
the cerebral cortex (Chang et al. 1974). However, only 3 of 16 animals exhibited incoordination and
weakness. Similarly, cats given gavage doses of methylmercuric chloride as low as 0.25 mg Hg/kg/day for
44–243 days displayed degenerative lesions in the granule and Purkinje cells of the cerebral cortex and/or
cerebellum and degenerative changes in the white matter, but no manifestations of neurotoxicity (ataxia,
loss of righting reflex, visual and sensory impairments) were observed until 0.5 mg Hg/kg/day was given
(Khera et al. 1974). Neonatal monkeys given 0.5 mg Hg/kg/day as methylmercuric chloride in infant
formula for 28–29 days exhibited stumbling and falling prior to termination of exposure (Willes et al.
1978). Despite the termination of exposure, abnormalities in the several reflexes; blindness; abnormal
behavior consisting of shrieking, crying, and temper tantrums; and coma developed. Histopathological
analyses showed diffuse degeneration in the cerebral cortex (especially the calcarine, insular, pre-, and
postcentral gyri, and occipital lobe), cerebellum, basal ganglia, thalamus, amygdala, and lateral geniculate
nuclei. Macaque monkeys exposed to methylmercuric chloride in biscuits exhibited tremors and visual
field impairment (Evans et al. 1977). These effects were observed in animals that were first administered
4–5 priming doses of 1 mg Hg/kg at 5-day intervals (no toxicity observed), followed by "maintenance"
doses of 0.5–0.6 mg Hg/kg once a week for 87–256 days. Squirrel monkeys developed similar symptoms
after receiving a single priming dose of 1 or 2 mg Hg/kg as methylmercuric chloride by gavage, followed
77 days later by maintenance doses of 0.2 mg Hg/kg once a week for 90–270 days (Evans et al. 1977). The
doses were adjusted to maintain steady-state blood mercury levels in the range of 1–4 ppm. No
tremors or convulsions were observed in female monkeys (Macaca fascicularis) during a 150-day exposure