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

MERCURY 147
2. HEALTH EFFECTS
less than controls for the 10, 20, and 30 mg/kg methylmercuric chloride groups, respectively. The LD 50 of
methylmercuric chloride for fetuses was determined to be 16.5 mg/kg. The backbones of fetuses were
severely curved at the high-dose level; mean fetal body lengths were reduced by 9.6, 21.7, and 48.8% in the
10, 20, and 30 mg/kg methylmercuric chloride groups, respectively, as compared to controls. Mercury
content in maternal organs was highest in kidneys, followed by blood, spleen, liver, and brain, while in fetal
organs it was highest in liver. Fetal liver and brain contained more mercury than maternal liver and brain;
however, fetal kidneys retained less mercury than maternal kidneys. The fetal ossification center was not
completely formed in sternebrae, particularly in the fifth and second bones, pelvic bones, and pectoral
phalanges of fetuses in rats treated with 30 mg/kg methylmercuric chloride. The ossified lengths of skeletal
bone stained with alizarin red S were developed least in the fifth sternebrae, metacarpals in the pectoral
girdle, and ischium in the pelvic girdle, and were severely retarded in development as position of the ribs
goes from the sixth bone (center) to the first and 13th bone (each edge) (Lee and Han 1995).
Four groups of 12 pregnant Sprague-Dawley rats were exposed to methylmercury or elemental mercury
alone or in combination as follows: one group was administered 2 mg/kg/day methylmercury via gavage
during Gd 6–9; another was exposed by inhalation to 1.8 mg/m 3 metallic mercury (elemental Hg) vapor for
1.5 hours per day during Gd 14–19; a third was exposed to both methylmercury by gavage (2 mg/kg/day,
Gd 6–9) and elemental Hg vapor by inhalation (1.8 mg/m3 , Gd 14–19) (methylmercury + elemental Hg); a
fourth group was given combined vehicle administration for each of the 2 treatments (control). The
inhalation regimen corresponded to an approximate dose of 0.1 mg Hg/kg/day. Maternal body weights
were monitored. At postpartum day 3, each litter was reduced to 4 male offspring. Body weight, pinna
unfolding, tooth eruption, and eye opening were monitored. Testing of behavioral function was performed
between 4 and 5 months of age and included spontaneous motor activity, spatial learning in a circular bath,
and instrumental maze learning for food reward. Surface righting reflex and negative geotaxis were
measured before weaning. There were no differences between any of the groups in maternal body weight
gain or in body weight, pinna unfolding, tooth eruption, surface righting reflex, and negative geotaxis in
offspring. Offspring of dams exposed to elemental mercury showed hyperactivity in the spontaneous motor
activity test chambers over all three of the following parameters: locomotion, rearing, and total activity.
This effect was potentiated in the animals of the methylmercury + elemental mercury group. In the swim
maze test, the methylmercury + elemental mercury and elemental mercury groups evidenced longer
latencies to reach a submerged platform, which they had learned to mount the day before, compared to
either the control or methylmercury groups. In the modified, enclosed radial-arm maze, both the methylmercury
+ elemental Hg and elemental Hg groups showed more ambulations and rearings in the activity