It was stated in WHO (1976) that there is no evidence
in the literature for the synthesis of organomercury com-
pounds in human or mammalian tissues. Minor methylation
may occur in vitro by intestinal or oral bacteria (Rowland
et al., 1975; Heintze et al., 1983). A slight increase in
the concentration of methylmercury in blood and/or urine
has been reported among dentists and workers in the
chloralkali industry (Cross et al., 1978; Pan et al.,
1980; Aitio et al., 1983). These data cannot be taken as
evidence of methylation, however, due to lack of analyti-
cal quality control and possible confounding by exposure
to methylmercury. Chang et al. (1987) did not observe any
methylation in a study of dentists.
The conversion of methylmercury to inorganic mercury
is considered a key step in the process of excretion of
mercury after exposure to methylmercury (WHO, 1990). If
the intact molecule of an organomercurial in an organ is
more rapidly excreted than inorganic mercury, biotrans-
formation will decrease the overall excretion rate, and
the ratio of inorganic to organic mercury in that particu-
lar organ will increase with time. The fraction of total
mercury present as Hg++ will depend on the duration of
exposure to methylmercury and/or the time elapsed since
cessation of exposure. Even if the demethylation rate is
very slow, this process may in the long run give rise to
considerable accumulation of inorganic mercury. The ratio
of methylmercury to inorganic mercury depends on the rate
of demethylation and the clearance half-times of methyl-
mercury and inorganic mercury.
After short-term exposure of experimental animals to
methylmercury the kidneys usually contain the highest
fraction of Hg++ in relation to total mercury, while the
relative concentration in the brain is low (WHO, 1976).
In studies on squirrel monkeys (Berlin et al., 1975), the
short-term biotransformation to inorganic mercury was as
follows: of the total mercury, about 20% was inorganic in
the liver; 50% in the kidney; 30%-85% in the bile; and
less than 5% in the brain.
More recent data from long-term studies on monkeys
show a different pattern. Mottet & Burbacher (1988) sum-
marized a long series of studies on the metabolism and
toxicity of methylmercury in monkeys (Macaca fascicu-
laris). The monkeys had been orally exposed to high levels
of methylmercury for a period of years and sacrificed
during the ongoing exposure. At the end of the exposure
period, 10-33% of the mercury in the brain was present in
the inorganic form (Lind et al., 1988). In monkeys that
had been without mercury exposure for 6 months to almost
two years after the same treatment, the relative concen-
tration of inorganic mercury was much higher, i.e. about
90%. Exact half-times for the different compounds could
not be established in the absence of data on the concen-
trations of inorganic and organic mercury in the brain at
different time intervals during the accumulation and
clearance phases. Recent data by Rice (1989) also demon-
strate demethylation in the brain. Female monkeys (Macaca
fascicularis) were dosed for at least 1.7 years with mer-
cury as methylmercury chloride (10-50 µg/kg per day).
After dosing ceased, the blood mercury half-time was about
14 days. Approximately 230 days after cessation of dosing,
the monkeys were sacrificed and brain total mercury levels
determined. These levels were considered to be at least
three orders of magnitude higher than those predicted by
assuming the half-time in brain to be the same as that in
blood. The author considered the most likely explanation
to be demethylation of methylmercury and subsequent bind-
ing of inorganic mercury to tissue.
Similar results were recently reported by Hansen et
al. (1989) who fed fish contaminated with methylmercury to
one Alsatian dog for 7 years. The dog was examined after
its death at the age of 12 years, 4 years after the
exposure to methylmercury had ceased. Two dogs of the same
age and breed served as controls. In the CNS, the mercury
was fairly uniformly distributed and 93% was in the inor-
ganic state, whereas the skeletal muscles contained
approximately 30% inorganic mercury. The authors concluded
that the results demonstrated time-dependent demethylation
and suggested a variation in the rate from one type of
tissue to another. High levels of mercury were demon-
strated by a histochemical method in the liver, thyroid
gland, and kidney, whereas practically no mercury was
found in any of the organs examined in the control dogs.
The distribution of inorganic mercury was determined by a
histochemical method for locating mercury in tissue
sections. Total mercury was analysed by flameless atomic
absorption and organic mercury by GC.
A considerable fraction of the mercury in human
brains is reported to be in the form of inorganic mercury.
Kitamura et al. (1976) analysed autopsy material from 20
Japanese subjects for total mercury using flameless atomic
absorption and for methylmercury using GC. The median
concentration of total mercury in the cerebrum was 0.097
mg/kg wet weight and of methylmercury 0.012 mg/kg wet
weight. The values for the cerebellum were similar. No
analytical quality control data were reported.
In a Swedish autopsy study covering six cases (Friberg
et al., 1986; Nylander et al., 1987), about 80% of the
mercury in the occipital lobe cortex was inorganic. The
concentration of inorganic mercury varied between 3 and
22 µg/kg wet weight. Both total mercury and inorganic
mercury were determined by the method of Magos (Magos,
1971; Magos & Clarkson, 1972). For quality control pur-
poses total mercury was also analysed by neutron acti-
vation analysis. In this study, however, the concen-
trations of mercury in the brain were considerably lower
than in the Japanese study. As has been discussed in sec-
tion 5.1.1, an association between the number of amalgam
fillings and total mercury concentration in the occipital
lobe has been found. Exposure to inorganic mercury from
dental fillings could explain the high proportion of inor-
ganic mercury in the Swedish study but not in the Japanese
study, as it seems reasonable to assume that the mercury
exposure from amalgam should be approximately the same in
the two countries. The exposure to methylmercury could,
however, easily differ considerably.
Takizawa (1986) reported the total mercury and methyl-
mercury brain concentrations in about 30 humans who had
died from 20 days to 18 years after the onset of symptoms
of methylmercury poisoning. The total mercury content was
measured by flameless atomic absorption spectrophotometry,
while methylmercury was analysed by electron capture GLC
(Minagawa et al., 1979; Takizawa, 1986). The total mercury
content in "acute" cases (autopsy < 100 days after onset
of symptoms) was 8.8-21.4 mg/kg and the concentration of
methylmercury was 1.85-8.42 mg mercury/kg. The concen-
trations for the "chronic" cases were 0.35-5.29 mg/kg
for total mercury and 0.31-1.02 mg mercury/g for methyl-
mercury. On average, only 28% of the mercury was present
as methylmercury in the acute cases and 17% in the chronic
cases. Takizawa (1986) also presented data for residents
near Minamata Bay and for a non-polluted area. The best
estimate from these data is that only 16% and 12%,
respectively, of the total mercury was present as methyl-
mercury.
