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

MERCURY 146
2. HEALTH EFFECTS
In animals, there is evidence of developmental effects following oral exposure to organic mercury during
gestation, lactation, and/or postweaning. Increases in several parameters indicative of developmental
toxicity have been observed. Not all studies have examined neurological end points, but developmental
neurotoxicity has been observed at very low exposure levels.
Methylmercuric chloride administered via gavage to pregnant rats at 8 mg Hg/kg on Gd 10 resulted in
increased skeletal variations (incomplete fusion of the sternebrae) (Fuyuta et al. 1979). At higher doses,
decreased fetal weight and increased malformations (cleft palate) were observed. Administration of lower
doses of methylmercury (4 mg Hg/kg/day) for a longer duration of gestation (Gd 7–9 or 6–14) resulted in
an increased incidence of rat fetuses with incomplete ossification or calcification (Nolen et al. 1972). The
incidence of skeletal variations at 0.2 mg/kg/day was not significantly different from controls. Methylmercuric
chloride administered to pregnant rats (n=10) via gavage at 2 mg Hg/kg/day throughout gestation
(Gd 0–20) resulted in increased numbers of malformed fetuses (Inouye and Murakami 1975). The most
common malformations were generalized edema and brain lesions. When methylmercuric chloride was
administration to pregnant rats at 4 mg Hg/kg/day during Gd 7–14, there was a decreased fetal weight and
an increased number of total malformations, hydrocephalus, and wavy ribs (Fuyuta et al. 1978). At 6 mg
Hg/kg/day, increased resorptions, fetal deaths, cleft palate, generalized edema, brain lesions, absence of
vertebral centra, and defects of the sternum were observed. Skeletal variations seen at 6 mg Hg/kg/day
included absence of one or more sternebrae, bipartite sternebrae, and bilobed vertebral centra.
Administration of a single dose of 24 mg Hg/kg as methylmercuric chloride to pregnant rats during
Gd 6–12 resulted in decreased fetal weights and increased malformations (Inouye and Murakami 1975).
The incidence of malformations (hydrocephalus, cleft palate, micrognathia, microglossia, generalized
edema, subcutaneous bleeding, and hydronephrosis and hypoplasia of the kidneys) increased with later
treatments (after Gd 7). Hydrocephalic brains had lesions in the brain mantle, corpus callosum, caudate
putamen, and primordial cerebellum. Brains without hydrocephalus had lesions in similar brain areas, as
well as dilation of the third ventricle and partial ablation of the ependymal lining.
Groups of 30 pregnant Fischer 344 rats were orally administered 10, 20, or 30 mg/kg methylmercuric
chloride dissolved in saline on Gd 7. Controls were given saline only (n=30). Maternal body weight gain
and deaths were monitored. Maternal body weights were decreased for 2 days in rats given 10 mg/kg as
methylmercuric chloride and for 6 days in rats given 20 mg/kg and were continuously decreased for those
given 30 mg/kg. Maternal death rates were 6.7, 16.7, and 30% in the 10, 20, and 30 mg/kg methylmercuric
chloride dose groups; no control dams died. Survival rates of fetuses were 19.2, 41.4, and 91.1%