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

MERCURY 151
2. HEALTH EFFECTS
Hg/kg/day, no effects were observed. Exposure to 6.4 mg Hg/kg as methylmercuric chloride on Gd 15
resulted in decreases in spontaneous locomotor activity, increased sensitivity to pentylenetetrazol-induced
convulsions, and a transient increase in γ-aminobutyric acid (GABA) and benzodiazepine receptors
(Guidetti et al. 1992). Using the same exposure paradigm, shorter avoidance latency was observed in 14-,
21-, and 61-day-old rats (Cagiano et al. 1990). Glutamate receptor binding affinity and dopamine receptor
number were also significantly affected in the brains of these offspring. Thus, multiple neurotransmitter
systems may participate in the neurological effects observed.
A sensitive test for neurological effects of gestational exposure to methylmercury is operant behavioral
performance (i.e., rewarded responses to total lever presses). Bornhausen et al. (1980) reported a significant
reduction in operant behavioral performance in 4-month-old rat offspring exposed to methylmercuric
chloride at 0.008 mg Hg/kg/day on Gd 6–9. A dose of 0.004 mg Hg/kg/day did not alter the behavioral
performance of the offspring. No other studies have confirmed this result to date.
Pregnant hamsters received single oral gavage doses of 2.5–63 mg Hg/kg as mercuric acetate on Gd 8 (Gale
1974). Decreased crown-rump length was observed at 5 mg Hg/kg, although this effect did not increase
linearly with the dose level. The incidence of resorptions increased at 22 mg Hg/kg and occurred in a doserelated
manner. Other effects that occurred at higher dose levels included growth-retarded or edematous
embryos. No significant developmental effects were evident at 2.5 mg Hg/kg.
Developmental neurotoxicity and changes in tissues, including the liver and immune system, have been
observed in studies in which exposure occurred prior to gestation and/or was continued after gestation for
intermediate durations. Retarded behavioral maturation (swimming behavior, righting reflexes) and
learning disability (maze learning) were demonstrated in rat offspring receiving a diet of 0.1 mg Hg/kg/day
(unspecified forms of mercury) in a contaminated fish diet from Gd 1 to postnatal day 42 (Olson and Boush
1975). Decreased performance in a paradigm intended to assess tactile-kinesthetic function (use of too
much force) was observed in offspring of rats exposed to 0.08 mg Hg/kg/day as methylmercuric chloride
for 2 weeks prior to mating through weaning (Elsner 1991). No morphological changes were observed in
the brains of the offspring of maternal rats given 0.195 mg Hg/kg/day as methylmercuric chloride for
14 weeks prior to mating through postpartum day 50 (Lindstrom et al. 1991). However, norepinephrine
levels in the cerebellum of offspring were significantly increased. Methylmercuric chloride at doses of
0.25 mg Hg/kg/day administered beginning several weeks prior to gestation resulted in an increase in the
incidence of unilateral or bilateral ocular lesions in the neonates, associated with histological changes in the