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

MERCURY 270
2. HEALTH EFFECTS
Rowens et al. 1991), but glomerular changes have also been reported (Kazantzis et al. 1962; Tubbs et al.
1982).
Although the primary effect of mercury on the kidneys appears to be a direct toxic effect on the renal tubules,
there is also evidence that implicates an immune mechanism of action for mercury-induced glomerular
toxicity in some persons. In support of this theory, a few human case studies have reported deposition of IgG,
immune complexes, and/or complement C3 along the glomerular basement membrane (Lindqvist et al. 1974;
Tubbs et al. 1982).
Studies in animals support the conclusion that the primary toxic effect of both inorganic and organic mercury
in the kidneys is on the epithelial cells of the renal proximal tubules. The changes observed in these studies
were comparable with those observed in humans (i.e., proteinuria, oliguria, increases in urinary excretion of
tubular enzymes, proteinaceous casts, decreased ability to concentrate the urine, decreased
phenolsulfonphthalein excretion, increased plasma creatinine) (Bernard et al. 1992; Chan et al. 1992; Dieter et
al. 1992; Girardi and Elias 1991; Jonker et al. 1993a; Kirschbaum et al. 1980; Nielsen et al. 1991; NTP 1993;
Yasutake et al. 1991b). In addition, the animal studies provided detailed information regarding the
histopathological changes occurring in the kidneys (Carmignani et al. 1989, 1992; Chan et al. 1992; Dieter et
al. 1992; Falk et al. 1974; Fitzhugh et al. 1950; Fowler 1972; Goering et al. 1992; Hirano et al. 1986; Jonker
et al. 1993a; Klein et al. 1973; Magos and Butler 1972; Magos et al. 1985; Mitsumori et al. 1990; Nielsen et
al. 1991; NTP 1993; Yasutake et al. 1991b). The progression of renal toxicity included initial degenerative
changes in the epithelial cells of the proximal tubules (nuclear swelling, increased eosinophilia/basophilia,
vacuolization, and cellular hypertrophy). In the early stages, these degenerative changes were accompanied
by tubular regeneration. Occasionally, when there is minor toxic damage, only the regenerative changes were
observed. As the lesions progressed, tubular dilation, desquamation of the epithelial cells, and thickening of
the tubular basement membrane were observed. Fibrosis, inflammation, necrosis, and atrophy of the tubules
and glomerular changes (i.e., hypercellularity, thickening of the glomerular basement membrane) were then
observed.
Several investigators have suggested that the renal toxicity exhibited after administration of organic forms of
mercury (e.g., methylmercury) may actually result from the in vivo metabolism of this form to inorganic
mercury (Fowler 1972; Klein et al. 1973; Magos et al. 1985). This hypothesis is supported by the increase in
the smooth endoplasmic reticulum, a potential site for this metabolic conversion, and the measurement of