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

MERCURY 182
2. HEALTH EFFECTS
Treatment of mice with ethanol results in increased accumulation of mercury in the fetus (Khayat and
Dencker 1982). The concurrent generation of NADPH during the oxidation of alcohol enhances the
reduction of mercuric ion to metallic mercury, making it more favorable for permeating the placenta.
Mercuric chloride's limited ability to cross the placental barrier was also demonstrated in an intravenous
study using mice (Inouye and Kajiwara 1990). Following intravenous dosing of mercuric chloride
(1.4 mg/kg) to pregnant mice on 1 day between days 9 and 17 of pregnancy, mercuric chloride was
transferred inefficiently to the fetus, being blocked almost completely by the fetal membrane. The mercury
accumulated in the placenta and yolk sac but not in the amnion or fetal body (Inouye and Kajiwara 1990).
A histochemical study demonstrated that mercuric mercury (Hg +2 ) was blocked in the proximal wall of the
yolk sac.
2.3.3 Metabolism
The available evidence indicates that the metabolism of all forms of mercury is similar for humans and
animals. Once absorbed, metallic and inorganic mercury enter an oxidation-reduction cycle. Metallic
mercury is oxidized to the divalent inorganic cation in the red blood cells and lungs of humans and animals.
Evidence from animal studies suggests the liver as an additional site of oxidation. Absorbed divalent cation
from exposure to mercuric mercury compounds can, in turn, be reduced to the metallic or monovalent form
and released as exhaled metallic mercury vapor. In the presence of protein sulfhydryl groups, mercurous
mercury (Hg + ) disproportionates to one divalent cation (Hg +2 ) and one molecule at the zero oxidation state
(Hg0 ). The conversion of methylmercury or phenylmercury into divalent inorganic mercury can probably
occur soon after absorption, also feeding into the oxidation-reduction pathway.
Metallic and Inorganic Mercury. Metallic mercury vapor is inhaled through the lungs and rapidly enters
the bloodstream. The dissolved vapor can undergo rapid oxidation, primarily in the red blood cells, to its
inorganic divalent form by the hydrogen peroxide-catalase pathway (Clarkson 1989; Halbach and Clarkson
1978). It is believed that the rate of oxidation is dependent on: (1) concentration of catalase in the tissue;
(2) endogenous production of hydrogen peroxide; and (3) availability of mercury vapor at the oxidation site
(Magos et al. 1978). In red blood cells in vivo, hydrogen peroxide production is probably a ratedetermining
step because Nielsen-Kudsk (1973) found that stimulation of hydrogen peroxide production in
red cells increased the uptake of mercury vapors in red blood cells. After a low dose, the total mercury
content in the blood is proportionately higher than (to the administered dose) after a high dose, indicating
that a higher proportion of the lower dose is oxidized (Magos et al. 1989). The hydrogen peroxide-catalase