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

MERCURY 183
2. HEALTH EFFECTS
pathway in red cells may become saturated at higher dose levels (Magos et al. 1989). This oxidation
pathway of metallic mercury can be inhibited by ethanol since ethanol is a competitive substrate for the
hydrogen peroxide catalase and, consequently, can block mercury uptake by red blood cells (Nielsen-Kudsk
1973).
The oxidation of metallic mercury may also occur in the brain, liver (adult and fetal) (Magos et al. 1978),
lungs (Hursh et al. 1980), and probably all other tissues to some degree (Clarkson 1989). In rat liver
homogenates, hydrogen peroxide catalase is the predominant oxidative pathway in tissues. Its capacity is
very high. Unlike oxidation in red cells, the rate-limiting step in in vitro oxidation in the liver is dependent
on the rate of mercury delivery to the enzyme (Magos et al. 1978). Unoxidized metallic mercury can still
reach the brain because the oxidation of metallic mercury is a slow process compared with the circulation
time from the lungs to the brain (Magos 1967). In the brain, unoxidized metallic mercury can be oxidized
and become trapped in the brain because it is more difficult for the divalent form to cross the barrier.
Autoradiographic studies suggest that mercury oxidation also occurs in the placenta and fetus (Dencker et
al. 1983), although the extent of oxidation is not known. The rate of distribution of metallic mercury to the
brain and fetus is probably nonlinear because the rate of oxidation in red cells is nonlinear (i.e., can become
saturated at higher doses) (Magos et al. 1989).
There is evidence to suggest that the divalent inorganic mercury cation is reduced by mammalian tissue to
metallic mercury after its oxidation. Rats and mice pretreated parenterally with mercuric chloride exhale
metallic mercury vapor (Clarkson and Rothstein 1964; Dunn et al. 1981a). Liver and kidney homogenates
in animals also release mercury vapor after exposure to mercuric chloride. The amount of mercury released
increases upon treatment with ethanol (Dunn et al. 1981b). This increase suggests that glutathione
reductase is responsible for mercuric ion reduction (Williams et al. 1982). Oxidation of alcohol to
acetaldehyde stimulates NADPH production, which is required for mercuric ion reduction. However,
alcohol is primarily oxidized in the liver, and this location is not consistent with the increases in metallic
mercury vapor released from the kidney homogenates (Dunn et al. 1981b).
Organic Mercury. Once absorbed, methylmercury can apparently be converted into inorganic mercury in
tissues, specifically the divalent cation (Hg +2 ) (Dunn and Clarkson 1980). Several investigators have
reported high levels of inorganic mercury in tissues (Magos and Butler 1972; WHO 1990) and feces after
methylmercury exposure (Turner et al. 1975). Rat liver microsomes can degrade methylmercury into
inorganic mercury. Inorganic mercury production from methylmercury paralleled the hydroxyl radical