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

MERCURY 282
2. HEALTH EFFECTS
Developmental toxicity has also been observed with parenteral exposure to methylmercury in pregnant dams
during gestation. In mice given methylmercuric hydroxide subcutaneously daily from Gd 7–12, significant
dose-related increases in the percentage of litters with resorptions were seen in groups receiving 3.45–8.6 mg
Hg/kg/day (Su and Okita 1976). The frequency of cleft palate increased significantly in litters of the
3.45 and 4.3 mg Hg/kg/day groups only. A high incidence of delayed palate closure and cleft palate was
also reported in mice injected subcutaneously with 5 mg Hg/kg of methylmercuric chloride on Gd 12 (Olson
and Massaro 1977). Gross incoordination and decreased frequencies of defecation and urination in pups
were observed following intraperitoneal administration of a single dose of methylmercury dicyandiamide
(8 mg/kg/day) to pregnant mice on day 7 or 9 of pregnancy (Spyker et al. 1972). Degenerative changes were
observed in the cerebellum and cerebral cortex of rat pups of maternal rats injected with 4 mg Hg/kg as
methylmercuric chloride on Gd 8 (Chang et al. 1977). Degenerative renal changes (in epithelial cells of
proximal tubules and Bowman's capsule of glomeruli) were reported in rat fetuses of dams exposed
intraperitoneally to methylmercuric chloride during Gd 8 (Chang and Sprecher 1976). The studies by
Spyker and Smithberg (1972) demonstrated strain differences in susceptibility to the developmental effects
of methylmercury dicyandiamide. Intraperitoneal administration of single doses of methylmercury
dicyandiamide (2, 4, or 8 mg/kg) to pregnant mice of strains 129 Sv/S1 and A/J during gestation resulted in
retardation of fetal growth and increased resorption of implants in both strains. Teratogenic effects,
primarily of the palate and jaw, were detected at all dose levels in 129 Sv/S1 mice, but only at the highest
dose in strain A/J. The differential effects of methylmercury were dependent on the strain, the dose of the
agent, and the stage of embryonic development.
Antilaminin antibodies induced by mercuric chloride have been demonstrated to be detrimental to the
development of cultured rat embryos (Chambers and Klein 1993). Based upon that observation, those
authors suggested that it might be possible for an autoimmune disease induced by a substance such as
mercury at an early age to persist into later life, acting as a teratogen independent of both dose-response
relationships and time of exposure, but that possibility remains to be experimentally demonstrated.
One developmental study of phenylmercury compounds was reported by Gale and Ferm (1971) in which
hamsters were injected intravenously with phenylmercuric acetate at doses ranging from 5 to 10 mg/kg on
Gd 8. With the exception of the lowest dose, all other doses induced increased resorption rates and edema,
along with a few miscellaneous abnormalities including cleft palate and exencephaly.