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

MERCURY 133
2. HEALTH EFFECTS
in the monkey, including dose-effect data, and a more systematic exploration of the pattern of behavioral
deficits in both primates and rodents.
Gilbert et al. (1996) used fixed interval/fixed ratio performance in adult monkeys to evaluate effects from
exposure in utero to methylmercury. The fixed interval/fixed ratio (FI/FR) schedule is considered to be a
sensitive indicator of neurotoxicity. In the present study, monkeys (Macaca fascicularis) were exposed in
utero to methylmercury. Maternal doses of methylmercury of 0, 50, 70, or 90 µg/kg/day (in apple juice)
(n=11, 9, 2, and 2, respectively) resulted in infant blood mercury levels at birth ranging from 1.04 to
2.45 ppm. Monkeys were tested on a multiple FI/FR schedule of reinforcement at 8–10 years of age. Four
FI/FR cycles were run per session. Pause time and run rate were calculated for FI and FR components, as
well as FI quarter-life and local FI response rates. Methylmercury treatment and sex effects were
investigated by fitting a linear orthogonal polynomial regression to each monkey's profile across sessions
and performing two-way ANOVAs on the resulting linear and intercept terms. Results from all treated
monkeys were combined and compared to the control group. There were no treatment-related effects on
either the fixed interval (FI) or fixed ratio (FR) component for pause time or run rate. Analysis of the
quarter-life revealed a significant treatment by sex effect as well as a main effect for sex. Post hoc t-tests
revealed a significant difference in quarter-life of treated male and female monkeys and a marginal
difference between treated and control males. The FI run rate of the male monkeys was significantly
greater than that of the female monkeys whereas the FR run rate of the males was marginally greater. These
results indicate that there may be a differential effect of methylmercury on male and female monkeys,
which could be interpreted as an effect on temporal discrimination. The authors concluded that adult
monkeys exposed to in utero methylmercury exhibited very limited sex-related effects on the FI/FR
intermittent schedule of reinforcement.
Typical neurotoxic signs observed in rats exposed to methylmercury include muscle spasms, gait
disturbances, flailing, and hindlimb crossing (Fuyuta et al. 1978; Inouye and Murakami 1975; Magos et al.
1980, 1985). These effects have been observed after acute-duration gavage dosing with methylmercury
concentrations at doses as low as 4 mg Hg/kg/day for 8 days (Inouye and Murakami 1975) and may not be
observed until several days after cessation of dosing (Inouye and Murakami 1975; Magos et al. 1985).
Histopathological examination of the nervous systems of affected rats has shown degeneration of cerebellar
granule cells and dorsal root ganglia (Magos et al. 1980, 1985) and degenerative changes in peripheral
nerves (Fehling et al. 1975; Miyakawa et al. 1974, 1976). Comparison of the effects of 5 doses of
8 mg Hg/kg/day as ethyl- or methylmercury showed dorsal root damage as well as flailing and hindlimb