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

MERCURY 271
2. HEALTH EFFECTS
substantial levels of inorganic mercury in the kidneys following exposure to methylmercury (Fowler 1972;
Klein et al. 1973).
In New Zealand White rabbits and in certain strains of mice and rats, a membranous glomerulonephropathy
was the predominant finding in the absence of significant tubular damage. This syndrome was characterized
by proteinuria, deposition of immune material (i.e., IgG and complement C3) in the renal mesangium and
glomerular blood vessels, and minimal glomerular cell hyperplasia (Aten et al. 1992; Druet et al. 1978;
Hirszel et al. 1985; Hultman and Enestrom 1992; Matsuo et al. 1989; Michaelson et al. 1985; Pelletier et al.
1990; Pusey et al. 1990; Roman-Franco et al. 1978; van der Meide et al. 1993). Deposition of antiglomerular
basement membrane antibodies has been observed in a susceptible strain of rat at subcutaneous doses of
mercuric chloride as low as 0.15 mg Hg/kg 4 days a week for 2 weeks (Michaelson et al. 1985). Increases in
urinary protein were not observed until 0.74 mg Hg/kg 4 days a week for 2 weeks. In mice, autoantibodies to
glomerular basement membrane were not observed, but deposition of IgG in the kidneys occurs as a result of
autoantibodies to nucleolar antigens (Hultman and Enestrom 1988). The immune basis for these responses is
covered in the section on immunological effects below. The susceptibility to this form of renal toxicity
appears to be governed by both MHC genes and nonMHC genes (Aten et al. 1991; Sapin et al. 1984). Among
rat strains, Brown-Norway, MAXX, and DZB strains showed susceptibility to renal damage, whereas Lewis,
M520, and AO rats did not (Aten et al. 1991; Druet et al. 1978; Michaelson et al. 1985). Among mouse
strains, SJL/N mice are susceptible to renal toxicity, whereas DBA, C57BL, and Balb/c mice are not
(Hultman and Enestrom 1992; Hultman et al. 1992). The apparent genetic basis for susceptibility to mercuryinduced
nephrotoxicity in experimental animals has important implications with regard to susceptible
subpopulations of humans.
Based on the above information, it is likely that persons exposed to sufficiently high concentrations of
mercury may experience renal tubular toxicity. Certain persons who are genetically predisposed may also
develop an immunologically based membranous glomerulonephritis.
Dermal Effects. Dermal reactions have been observed in persons exposed to inorganic and organic
mercury following inhalation, oral, and/or dermal exposures. The predominant skin reaction is
erythematous and pruritic skin rashes (Al-Mufti et al. 1976; Aronow et al. 1990; Bagley et al. 1987; Biro and
Klein 1967; Bluhm et al. 1992a; Engleson and Herner 1952; Faria and Freitas 1992; Foulds et al. 1987; Goh
and Ng 1988; Hunter et al. 1940; Jalili and Abbasi 1961; Kang-Yum and Oransky 1992; Karpathios et al.
1991; Morris 1960; Pambor and Timmel 1989; Schwartz et al. 1992; Sexton et al. 1976;