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

MERCURY 137
2. HEALTH EFFECTS
as low as 0.046 mg Hg/kg/day for 2 years exhibited neurobehavioral toxic signs, including mild impairment
of motor activity and diminished sensitivity to pain (Charbonneau et al. 1976). These effects began after
60 weeks of exposure but did not progress during the remainder of the 2 years of exposure. At higher doses
of 0.074 and 0.18 mg Hg/kg/day, ataxia, alterations in gait, motor incoordination, muscle weakness,
changes in temperament, and convulsions were also observed. Histopathological analyses showed neuronal
degeneration in the motor, sensory, auditory, and occipital cortices and cerebellar granule cell degeneration.
Five monkeys fed 0.05 mg Hg/kg/day as methylmercuric chloride from birth until the age of 3–4 years
displayed impaired spatial vision at that time (Rice and Gilbert 1982). Continued dosing until 6.5–7 years
of age resulted in clumsiness, decreased fine motor performance, and insensitivity to touch when tested at
13 years of age (Rice 1989c). Impaired high-frequency hearing was also displayed by these monkeys when
tested at 14 years of age (Rice and Gilbert 1992). It is noteworthy that a wide range of neurotoxic
symptoms (motor, visual, and auditory) were observed in a species similar to humans several years after
dosing had ceased. No clinical signs or histopathological evidence of neurotoxicity was observed in rats
that received 0.1 mg Hg/kg/day as methylmercuric chloride in the diet for 2 years (Verschuuren et al. 1976).
Deficiencies in many of the studies make it difficult to fully evaluate the quality of the data reported.
General problems include the following: (1) many details of experimental protocols were omitted, thereby
prohibiting an evaluation of the study's adequacy; (2) very often, only one dose was used, so an analysis of
any possible dose-response relationships was not possible, and the possibility that certain observed effects
were not compound-related cannot be excluded; (3) control data often were not presented; and (4) the
results were frequently described in subjective terms, and no attempt was made to quantitate the data.
Despite these limitations, animal studies do provide irrefutable evidence that the central and peripheral
nervous systems are target organs for organic mercury-induced toxicity.
In summary, methylmercury is neurotoxic to humans and to several species of experimental animals
following acute, intermediate, and chronic oral exposure. The major effects that are seen across the studies
include motor disturbances, such as ataxia and tremors, as well as signs of sensory dysfunction, such as
impaired vision. The predominant neuropathological feature is degenerative changes in the cerebellum,
which is likely to be the mechanism involved in many of the motor dysfunctions. In humans, disruptions of
higher functions have also been noted, as evidenced by depression and irritability.