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

MERCURY 115
2. HEALTH EFFECTS
(dilated tubules with either flattened eosinophilic epithelial cells or large cytomegalic cells with foamy
cytoplasm) at 14.3 mg Hg/kg/day (Dieter et al. 1983).
In a 6-month exposure to 0.23–3.7 mg Hg/kg/day, a significant increase in severity of nephropathy (i.e.,
dilated tubules with hyaline casts, foci of tubular regeneration, and thickened tubular basement membrane)
was observed in Fischer 344 rats exposed to 0.93 mg/kg/day of mercuric chloride compared to the controls
(NTP 1993). The absolute and relative kidney weights were increased in males at 0.46 mg/kg/day. In
B6C3F1 mice, the incidence and severity of cytoplasmic vacuolation of renal tubule epithelium increased in
males exposed to at least 3.7 mg Hg/kg/day as mercuric chloride for 6 months (NTP 1993). Administration
of large doses of mercuric chloride (28 mg Hg/kg/day) in the drinking water for 6 months also resulted in
focal degeneration of the tubular cells with decreased acid phosphatase in the lysosomes (indicative of the
release of the lysosomal contents) (Carmignani et al. 1992). Notably, at this dose, renal glomerular changes
were also evident. The glomeruli showed hypercellularity, and there was deposition of amorphous material
in the mesangium; thickening of the basement membrane with IgM present was also observed.
When a strain of mice (SJL/N) sensitive to the immunotoxic effects of mercury was given mercuric chloride
in the drinking water at 0.56 mg Hg/kg/day for 10 weeks, slight glomerular cell hyperplasia with granular
IgG deposits in the renal mesangium and glomerular blood vessels were observed (Hultman and Enestrom
1992). No tubular necrosis was observed.
In a 2-year study, male rats gavaged with 1.9 or 3.7 mg Hg/kg/day as mercuric chloride 5 days a week
exhibited an incidence of marked nephropathy (described as thickening of glomerular and tubular basement
membranes and degeneration and atrophy of tubular epithelium) that was significantly greater in severity
than in the control group (NTP 1993). In addition, the incidence of renal tubule hyperplasia was increased in
the high-dose male rats. In the same study, the incidence and severity of nephropathy were significantly
greater in male and female mice gavaged with 3.7 and 7.4 mg Hg/kg/day as mercuric chloride 5 days a week
than in the controls. Administration of 7 mg Hg/kg/day as mercuric chloride to rats in the drinking water
resulted in hydropic degeneration and desquamation of tubule cells (Carmignani et al. 1989). Electron
microscopy showed lysosomal alterations in the proximal tubules and thickening of the basal membrane of
the glomeruli.