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

MERCURY 148
2. HEALTH EFFECTS
test prior to the learning test. During the learning trial, the same groups (i.e., methylmercury + elemental
mercury and elemental mercury) showed longer latencies and made more errors in acquiring all eight
pellets. Generally, the results indicate that co-exposure to methylmercury, which by itself did not alter
these functions at the dose given in this study, served to significantly enhance the effects of prenatal
exposure to elemental mercury (i.e., alterations to both spontaneous and learned behaviors). Brain mercury
concentrations in offspring were 1 ng/g w/w in the controls, 4 ng/g in the methylmercury group, 5 ng/g in
the elemental mercury group, and 12 ng/g in the methylmercury + elemental mercury group (Fredriksson et
al. 1996).
Pregnant Sprague-Dawley rats were treated by gavage with a single oral dose of 8 mg/kg of methylmercury
chloride or saline on Gd 15. Within 24 hours after birth, litters were reduced to 6 pups per litter. Pups were
weighed weekly and weaned 21 days after birth. Offspring of control and treated rats were killed at 14, 21,
and 60 days of age. The binding characteristics of muscarinic receptors labeled in cortical membrane
preparation by [3H]-L-quinuclidinyl benzilate were studied, and the mercury level in the same brain area
was assessed. Total mercury content in cortical tissues was determined at 21 and 60 days of age.
Furthermore, the performance in passive avoidance tasks was evaluated in 10 rats from each group at
8 weeks of age. No differences in mortality or weight gain were observed in methylmercury-exposed pups
compared to controls. At 21 days of age, the level of mercury in the cortex was about 30 times higher in
exposed rats than in controls (190.2 ng/g w/w versus 6.4 ng/g); at 60 days, mercury levels did not differ
significantly (7.4 versus 5 ng/g, respectively). Perinatal exposure to methylmercury significantly reduced
the maximum number of muscarinic receptors (Bmax) in the brain of 14-day-old (53%) and 21-day-old
(21.3%) rats, while there was no notable difference in 60-day-old rats. This phenomenon seems to be
strictly related to the presence of mercury in the cortex since it disappeared with the normalization of
mercury levels in the brain. Despite the recovery of muscarinic receptor densities in methylmercury-
exposed rats at 8 weeks of age, the avoidance latency was reduced in passive avoidance tests, indicating
learning and memory deficits in these animals (Zanoli et al. 1994).
Similar effects were observed in mice exposed to organic mercury. Methylmercuric chloride administered
orally by gavage to mice at 5 mg Hg/kg/day during Gd 6–17 resulted in 100% stillbirths or neonatal deaths
and the failure of 6 of 9 dams to deliver, with no apparent maternal toxicity (Khera and Tabacova 1973). At
lower doses (2 and 4 mg Hg/kg/day) for a shorter duration during gestation (days 6–13), no increase in
deaths or resorptions was observed, but increases in malformations, skeletal variations, and delays in
ossification were observed (Fuyuta et al. 1978). A higher dose of methylmercuric chloride (16 mg Hg/kg)