Chemistry Reference
In-Depth Information
and renal damage appearing as a tubular dysfunction
with tubular necrosis in severe cases. The lethal dose in
man is approximately 1 g of mercuric salt. The mercury
load on the kidney is best determined by analysis of
renal biopsy. Mercury concentrations in the kidney be-
tween 10 and 70 mg/kg have been reported in poison
cases with renal injury. Levels <3 mg/kg may be found
in normal cases. Occasionally, mercuric compounds
may cause idiosyncratic skin symptoms, which may
develop into severe exfoliative dermatitis or may cause
glomerular nephritis. Animal and clinical observations
have shown that mercuric mercury stimulates and
methylmercury inhibits the immune system A specifi c
form of idiosyncrasy, called acrodynia or pink disease,
is seen in children. Most cases are associated with mer-
cury exposure where increased levels of mercury in
urine are observed.
The hazards involved in long-term intake of food
containing methylmercury and in occupational expo-
sure to methylmercury are due to the effi cient ab-
sorption (90%) of methylmercury in man and the
long retention time (half-life of 70 days) with an
accumulation of methylmercury in the brain. Chronic
poisoning results in degeneration and atrophy of the
sensory cerebral cortex, paresthesia, ataxia, hearing,
and visual impairment. Prenatal exposure causes
cerebral palsy and, in less severe cases, psychomotor
retardation. Methylmercury concentration in blood
and hair refl ects the body burden and the concentra-
tion in brain of methylmercury. Intake resulting in
body burdens of <0.5 mg/kg body weight is not likely
to give rise to detectable neurological signs in adults.
This intake corresponds to blood values of <200
1 INTRODUCTION
Mercury (Hg) is a metal that is in liquid state at
room temperature. In addition to its metallic state,
mercury occurs in compounds as monovalent mercur-
ous mercury and divalent mercuric mercury. Mercury
also exists in nature as organometallic compounds in
which mercury is covalently bound to carbon, in com-
pounds of the type RHg+ and RHgR', where R and
R' represent the organic moiety. The carbon-mercury
bond is chemically stable because of the low affi nity of
mercury for oxygen.
The affi nity of mercury for sulfur and sulfhydryl
groups is a major factor underlying the biochemi-
cal properties of mercury and mercury compounds.
The mercury-containing moiety binds to sulfhy-
dryl groups of proteins in membranes and enzymes,
thereby interfering with membrane structure and
function and with enzyme activity. The toxicological
properties of the different forms of mercury (Hg) in
mammalian organisms are largely a function of the
complex binding interactions that occur between mer-
curic ions and various protein and nonprotein thiols
in the extracellular and intracellular compartments of
target cells. Because of the predilection of mercurous
or mercuric ions binding to sulfhydryl groups, as well
as other nucleophiles, there is an extremely low proba-
bility of these ions existing in an unbound, “free” ionic
state in extracellular and intracellular compartments
of the body (Hughes, 1957). Instead, ionic species of
Hg have a particular propensity to bind to the sulf-
hydryl groups on glutathione (GSH), cysteine (Cys),
homocysteine (Hcy),
N
-acetylcysteine (NAC), metal-
lothionein (MT), and albumin. In the presence of an
excess of low molecular weight, thiol-containing mol-
ecules, mercuric ions will bind to these molecules in a
linear I or II coordinate covalent manner, depending
on the species of mercuric ion (Canty
et al
., 1994; Fuhr
and Rabenstein, 1973; Rubino
et al
., 2004). Mercuric-
thiol conjugates formed in an aqueous environment
have been shown to be thermodynamically stable at
pH 1-14 (Fuhr and Rabenstein, 1973). It should also be
stressed that the formation constant for the thiol-Hg
bond is as much as 10 orders of magnitude greater
than the constant for the bonds formed between
mercuric ions and other nucleophiles present in the
same environment (Zalups, 2000a).
All forms of Hg induce toxic effects in mammalian
species, including humans. The extent of the adverse
effects induced by Hg depends on the form of Hg at
the time of exposure, the duration of exposure, and the
route of exposure. Toxic effects of Hg have been dem-
onstrated in the cardiovascular system (Carmignani
et al
., 1992; Soni
et al
., 1992; Wakita, 1987; Warkany
g/L
and mercury levels in hair of <50 mg/kg. However,
this level of methylmercury exposure in pregnant
women may result in inhibited brain development of
the fetus with psychomotor retardation of the child.
The highest level of methylmercury load in pregnant
women, not associated with inhibition of fetal brain
development, is not known.
The history of mercury has been reviewed by
Goldwater (1972). The pharmacology and toxicology
of mercury has been previously reviewed by Clark-
son
et al
. (1972), the chemistry of mercury in biological
systems by Carty and Malone (1979), the toxicology
of methylmercury by a Swedish Expert Group (1971),
and the toxicology and epidemiology by Friberg and
Vostal (1972), by the Task Group on Metal Accumu-
lation (1973), by the Task Group on Metal Toxicity
(1976), and by the WHO (1976; 1980; 1990; 1991). More
recently, the toxicology of mercury has been reviewed
in the USEPA Report to Congress (1998), ATSDR
(1999), NAS/NRC (2000), and IOM Report on Mercury
in Vaccines (2004).
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