Mercury - Toxicology of Metals - page 700

not show any adverse effects of the maternal expo-
sure from fi sh consumption (Davidson et al ., 1998;
Huang et al ., 2004; Myers et al ., 2003). The average
maternal Hg content in hair during pregnancy was
6.9 (SD, +4.5) ppm; range, 0.5-26.7 ppm. The cohort
was tested with an age-specifi c comprehensive neu-
ropsychological test battery every third year. There
are several possible explanations to the differences
in results between the two largest cohort studies. The
question about the size of the risk of neurodevelop-
ment interference by MeHg exposure resulting in
maternal hair levels below 10 ppm remains open. It
is, however, important to point out that all the men-
tioned epidemiological studies have been performed
on populations with frequent amalgam bearers. The
release of mercury vapor from dental restorations
may be an important confounder, so far uncontrolled
for. Mercury vapor causes in animal experiments the
same toxic signs and brain pathology at fetal exposure
as MeHg has an additive effect at concomitant expo-
sure to MeHg and is approximately 10 times more
toxic in terms of brain concentration of Hg needed for
adverse effect (see also preceding).

tion between consumption of contaminated fi sh and
prevalence of neurological symptoms, such as ataxia,
was found (Health and Welfare, Canada, 1979; Meth-
ylmercury Study Group, 1980). The results from these
two epidemiological studies indicate that exposure over
decades may result in brain damage, although blood
concentrations of MeHg never rise to those observed in
more acute epidemics of MeHg poisoning.

7.1.5.4 Incidence of Signs and Symptoms of MeHg
Poisoning Related to Concentration of MeHg in the Brain
Few data on concentrations of MeHg in the brains
of fatalities from the epidemic in Japan have been
reported. Almost no data are available from the
extensive epidemic in Iraq. The lowest concentrations
reported from Japan (Swedish Expert Group, 1971)
are in the order of 5 mg/kg in brain tissue. This value
can be estimated to correspond to approximately
800 g/L in blood, and approximately 200 mg/kg

in hair. These values are rather low in comparison to
dose-response relationships for early signs like par-
esthesia. No basis for the estimation of the mortality
rate exists at this level. The MeHg concentration in
the brain that corresponds to 200 ng/g in blood or
the lowest concentration at which neurological signs
have been observed can be calculated to lie between
1 and 2 mg/kg on the basis of the data cited previ-
ously. This concentration can be compared with data
from animal experiments in which the lowest concen-
tration seen gives rise to objectively recorded changes
in the CNS. Mattson et al . (1981) found that the lowest
concentration in a dog at which clear effects on “vis-
ual evoked response” in the visual cortex could be
observed was 1.28 mg/kg. These authors also found
pronounced histopathological changes in the brain
tissue at 8-15 mg/kg in the dog. Such changes in the
“visual evoked response” have also been observed in
patients from Niigata and Minamata (Tsubaki and Iru-
kayama, 1977). A sudden 50% increase in brain/blood
mercury concentration ratio was observed with increas-
ing MeHg levels in the blood of Squirrel monkeys
with brain concentration approximately 2.5 mg/kg
and MeHg in blood approximately 1000

µ

7.1.5.2 The Relationship Between Daily
Intake and Biological Index for MeHg
The relationship between daily intake of MeHg and
the concentration of MeHg reached at steady state is
still under debate. Epidemiological studies involv-
ing studies of food intake have resulted in values of
0.3-0.8 for the relation between MeHg intake and
MeHg concentration in blood expressed in

g/L or
day at 70-kg body weight (reviewed by the WHO in
1976). In experimental short-term studies on man,
this quotient has been found to be close to 1 (Kershaw
et al ., 1980; Miettinen; 1973).

µ

7.1.5.3 The Infl uence of Exposure Duration
on the Incidence of Signs and Symptoms of
Postnatal MeHg Poisoning
Most epidemiological data concerning MeHg poi-
soning are derived from studies of acute epidemics that
occurred in Japan and Iraq. In two epidemiological stud-
ies, data concerning more long-term exposure (Tsubaki
and Irukayma, 1977; Tsubaki et al ., 1978) have been col-
lected from a follow-up study of the Niigata epidemics
10-15 years after the exposure event. They reported that
signs appeared with very long latency at low levels of
exposure. Similar experiences have arisen from animal
experiments on primates. In another study on Canadian
Indians, who over a very long period were exposed sea-
sonally to MeHg and who had blood concentrations of
MeHg probably not exceeding 700

g/L. This
change coincided with a subcortical autoradiographic
accumulation of radioactive mercury in the brain and
development of neurological signs (Berlin et al ., 1975).
This observation indicates a change in toxicokinetics,
which may be due to change of the blood-brain bar-
rier, a saturation of elimination routes, or both. The
subcortical accumulation seems to support the sec-
ond alternative. Brain concentrations of Hg approxi-
mately 2 mg/kg was found in offspring prenatally
exposed and with pronounced brain pathology with
migration disturbances (Lögdberg et al ., 1993).

µ

µ g/L and seldom

exceeding 200 µ g/L, a statistically signifi cant associa-