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

MERCURY 117
2. HEALTH EFFECTS
glomeruli at the light microscopic level (Fowler 1972). The author concluded that these changes could be a
result of metabolism to inorganic mercury and may account for proteinuria observed in exposed humans.
Administration of methylmercuric chloride in the diet of mice for 26 weeks at a dose of 0.6 mg Hg/kg/day
resulted in degeneration of the proximal tubules characterized by nuclear swelling and vacuolation of the
cytoplasm (Hirano et al. 1986).
Rats fed daily doses of phenylmercuric acetate for up to 2 years exhibited slight-to-moderate renal damage
(e.g., tubular dilatation, atrophy, granularity, fibrosis) (Fitzhugh et al. 1950). These effects were evident at
doses (beginning at 0.02 mg Hg/kg/day) that were two orders of magnitude lower than those required to
induce detectable effects in the mercuric acetate-treated rats (Fitzhugh et al. 1950). A NOAEL of
0.005 mg Hg/kg/day was determined. The authors concluded that some of the histological changes were
present to some degree in the control animals, suggesting that low levels of mercury apparently hasten the
normal degenerative processes of the kidneys (see Inorganic Mercury above). Problems in this study limit
its usefulness in determining effect levels. Increased severity of renal nephrosis was also observed in
another study in which rats were given 0.4 mg Hg/kg/day as phenylmercuric acetate in the drinking water for
2 years (Solecki et al. 1991). Lower doses in this study were not tested. Mice given methylmercuric
chloride in the diet at a dose of 0.13 mg Hg/kg/day showed epithelial cell degeneration and interstitial
fibrosis, with ongoing regeneration of the tubules present (Mitsumori et al. 1990); no effect was observed at
0.03 mg Hg/kg/day. Similar effects were seen in mice given methylmercuric chloride in the diet for 2 years
at a dose of 0.11 mg Hg/kg/day (Hirano et al. 1986). Rats given methylmercuric chloride in the diet for
2 years at a dose of 0.1 mg Hg/kg/day had increased kidney weights and decreased enzymes (alkaline
phosphatase, ATPase, NADH- and NADPH-oxidoreductase, and AMPase) in the proximal convoluted
tubules (Verschuuren et al. 1976). However, histopathological examination revealed no treatment-related
lesions.
A 2-year study conducted with mercuric acetate in the feed of rats showed an increased severity of renal
damage at doses of mercury as low as 2 mg Hg/kg/day (Fitzhugh et al. 1950). Rats initially showed
hypertrophy and dilation of the proximal convoluted tubules. At this stage, eosinophilia, rounding, and
granular degeneration of the epithelial cells were observed. Occasionally basophilic cytoplasm and
sloughing of the cells were observed. As the lesion progressed, tubular dilation increased, and hyaline casts
appeared within the tubules; fibrosis and inflammation were observed. Finally, tubules appeared as cysts,
and extensive fibrosis and glomerular changes were observed. However, this study was limited because