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

MERCURY 126
2. HEALTH EFFECTS
Acute- and intermediate-duration studies describing neurotoxic effects in animals following exposure to
inorganic mercury salts are limited. A study was conducted by Chang and Hartmann (1972b) in which
mercuric chloride was administered both by gavage and subcutaneously. Evidence of disruption of the
blood-brain barrier (i.e., leakage of dye into the brain tissue) was observed 12 hours after a single dose of
0.74 mg Hg/kg as mercuric chloride in rats (Chang and Hartmann 1972b). These investigators also
administered 0.74 mg Hg/kg/day as mercuric chloride to rats for up to 11 weeks. Within 2 weeks, there
were coagulative or lucid changes in cerebellar granule cells and fragmentation, vacuolation, and
cytoplasmic lesions in the neurons of dorsal root ganglia. Neurological disturbances consisted of severe
ataxia and sensory loss, with an accompanying loss in body weight. No conclusions regarding the oral
neurotoxicity of mercuric chloride can be drawn from the results of this study because the discussion of the
results observed in the study did not clearly differentiate whether the effects were observed as the result of
oral or subcutaneous exposure. It is expected that mercuric chloride administered subcutaneously would be
much more toxic than that administered orally because of the very poor absorption of inorganic forms of
mercury from the gastrointestinal tract.
Dietary exposure of rats to 2.2 mg Hg/kg/day as mercuric chloride for 3 months resulted in inactivity and
abnormal gait (Goldman and Blackburn 1979). However, it is unclear whether the effects observed in this
study were the direct result of effects on the nervous system, or whether they may have been secondary to
other toxic effects. No evidence of neurotoxicity (clinical signs of neurotoxicity and optic and peripheral
nerve structure) was seen in mice administered 0.74 or 2.2 mg Hg/kg/day as mercuric chloride in the
drinking water for 110 days (Ganser and Kirschner 1985). The investigators increased the dose
administered to the low-dosed animals to 7.4–14.8 mg Hg/kg/day for an additional 400 days; however, still
no neurotoxic effects were observed. Similarly, no histopathological evidence of brain lesions was
observed in rats receiving gavage doses of mercuric chloride as high as 3.7 mg Hg/kg/day 5 days a week for
up to 2 years or in mice receiving gavage doses as high as 7.4 mg Hg/kg/day 5 days a week for up to
2 years (NTP 1993).
The highest NOAEL values and all reliable LOAEL values for neurotoxic effects in each species and
duration category are recorded in Table 2-2 and plotted in Figure 2-2 for inorganic mercury.
Organic Mercury. Most of the information concerning neurotoxicity in humans following oral exposure to
organic mercury comes from reports describing the effects of ingesting contaminated fish or fungicidetreated
grains (or meat from animals fed such grains). Information about doses at which the effects