The Panel on Health Risks and Toxicological Effects of Methylmercury:
Donna Mergler, Henry A. Anderson, Laurie Hing Man Chan, Kathryn R. Mahaffey, Michael Murray,
Mineshi Sakamoto and Alan H. Stern
Methylmercury Exposure and Health Effects in
Humans: A Worldwide Concern
The paper builds on existing literature, highlighting
current understanding and identifying unresolved issues
about MeHg exposure, health effects, and risk assess-
ment, and concludes with a consensus statement.
Methylmercury is a potent toxin, bioaccumulated and
concentrated through the aquatic food chain, placing at
risk people, throughout the globe and across the socio-
economic spectrum, who consume predatory fish or for
whom fish is a dietary mainstay. Methylmercury devel-
opmental neurotoxicity has constituted the basis for risk
assessments and public health policies. Despite gaps in
our knowledge on new bioindicators of exposure, factors
that influence MeHg uptake and toxicity, toxicokinetics,
neurologic and cardiovascular effects in adult popula-
tions, and the nutritional benefits and risks from the large
number of marine and freshwater fish and fish-eating
species, the panel concluded that to preserve human
health, all efforts need to be made to reduce and
eliminate sources of exposure.
The Panel on Health Risks and Toxicological Effects of
Methylmercury received the mandate to describe and synthesize
current scientific knowledge on methylmercury (MeHg) expo-
sure and its effects in humans and to identify research gaps. The
present paper is not intended to be a comprehensive review and
presentation of all the literature on MeHg exposure and effects
in humans but builds on earlier literature, other reviews, and
more recent literature in highlighting the current understanding
in the field and what we consider to be remaining unresolved
issues. Humans are exposed to different forms of mercury (Hg),
and potential health risks from forms other than MeHg can
occur, including mercury vapor from dental amalgams, as well
as from occupational exposures (e.g., dental offices, chloralkali
plants, fluorescent lamp factories, mercury mining) and from
artesanal and small-scale gold and silver mining operations (1–
5), the present document does not cover these exposures,
because the pathways of exposure and effects differ from those
for MeHg. Here, we examine issues of MeHg exposure, studies
on its health effects and major risk assessments, and conclude
with our consensus statement.
Sources of exposure. Methylmercury contamination poses a
particular challenge to public health because this toxicant is
mainly contained in fish, a highly nutritious food, with known
benefits for human health. Moreover, fish are culturally vital for
many communities and constitute an important global com-
modity. Although we often refer to ‘‘fish’’ in a generic way, all
fish do not have similar amounts of mercury. As a result of
bioaccumulation of MeHg through multiple levels of the
aquatic food web, higher tropic-level pelagic fish can be
contaminated with MeHg at concentrations in excess of 1 part
per million (ppm). The concentrations of total Hg vary widely
across fish and shellfish species, with the mean values differing
by as much as 100-fold (6). Methylmercury is bound to proteins,
as well as to free amino acids, that are components of muscle
tissues, and are not removed by any cooking or cleaning
processes that do not destroy muscle tissues.
Although in general, MeHg accumulates in fish through the
food chain, consumption of farmed fish can also lead to MeHg
exposures, in part, because of the presence of MeHg in feed (7).
Some studies have shown no significant difference in MeHg
levels in farmed vs. wild salmon, although concentrations in both
cases are relatively low (8, 9). Although fish and shellfish are the
predominant sources of MeHg in the diets of humans and
wildlife, a few reports of other sources exist. Rice cultivated in
areas contaminated with mercury can contain relatively high
levels of MeHg (10). Methylmercury has also been reported in
organ meats of terrestrial animals (11), as well as in chicken and
pork, probably as a result of the use of fish meal as livestock feed
(12). Some communities also have higher MeHg exposure
because of the consumption of fish-eating marine mammals
Profiles of exposure. Although most reports on MeHg
exposure focused on specific populations generally assumed to
have high levels of fish consumption, estimates of general
populations exposure exist for the United States (15, 16),
Germany (17), and Japan (18) [summarized in Pirrone and
Mahaffey (19)]. For populations that are not selected on the
basis of high fish consumption, mean hair Hg levels generally
range from .0.1 lg g?1to ,1.0 lg g?1(20–25). The mean blood
Hg for such populations is generally in the range of ,1.0 lg L?1
to ,5.0 lg L?1, although, worldwide there are fewer data on
MeHg exposure based on blood than on hair. In the United
States nationally, about 5–10% of the population of women of
childbearing age have hair levels exceeding 1.0 lg g?1(16) and
blood levels exceeding 5 lg L?1(26). In Japan, where more fish
is consumed, 73.7% of women of this age have hair levels above
1.0 lg g?1and 1.7% above 5 lg g?1(18). In Germany, the 1998
geometric mean blood level was 0.58 lg L?1(17).
High levels of Hg exposure were identified in numerous fish-
eating populations throughout the world [for reviews see:
Pirrone and Mahaffey (19)]. Many of these live near oceans,
major lakes and rivers, or hydroelectric dams, and are often
dependent on local catch, with fish an integral part of their
cultural traditions. In the sea islands of the Faroes and
Seychelles, median mothers’ hair Hg concentrations were 4.5
lg g?1[with 27% above 10 lg g?1(27)] and 5.8 lg g?1(28),
respectively. In the river basins of the Amazon, where a large
number of studies was carried out on populations for whom
freshwater fish is a dietary mainstay, median hair Hg levels
typically range between 5 lg g?1and 15 lg g?1(29–34).
Despite the importance of local catch, fish is also a global
commodity and market fish, such as shark, tuna, and swordfish,
or canned white tuna (35), consumed by persons living far away
from the source can likewise have high levels of MeHg. In the
United States, individuals with high blood Hg concentrations
were reported among affluent urbanites who ate large quantities
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? Royal Swedish Academy of Sciences 2007
of marine fish, high in the food web (36, 37). Thus, elevated
MeHg exposure is present around the globe, with no
geographic, social, economic, or cultural boundaries.
Biomarkers of MeHg exposure. Hair and blood Hg
concentrations are both accepted as valid biomarkers of MeHg
exposure, although each provides a somewhat different
reflection of exposure (38). Blood gives an estimate of exposure
over the most recent one to two half-lives, with the half-life of
MeHg in blood being 50–70 days, whereas hair reflects the
average exposure over the growth period of the segment (28).
Hair Hg is predominantly MeHg, with MeHg constituting from
80% to 98% of hair total Hg (33, 39). For populations with
regular and frequent fish consumption, hair total Hg and blood
MeHg are consistently correlated (40). Generally, hair is 250 to
300 times more concentrated in mercury than is blood (39).
However, in populations and individuals with infrequent fish
consumption or where bolus doses of MeHg occur, there can be
considerable inter- and intraindividual variability in the relation
between hair and blood Hg levels resulting from temporal
differences in the retention of Hg by each biomarker (33, 40,
41). Segmental analyses of hair Hg can provide a chronology of
exposure over time (24, 28, 29, 33). However, information on
short-term peaks in exposure is not well represented by such
analyses (38). Another consideration is that the growth rate of
hair, generally estimated at 1 cm mo?1, can have both inter-and
intraindividual variability (38). Recent advances in a single hair-
strand analysis (42), including measurement of Hg at micron
resolution by using laser ablation (43) should yield more
information on the relation between Hg uptake and Hg
deposition in hair.
The Hg levels in toenails and fingernails also were used as
biomarkers of Hg exposure, mostly in major studies of the
cardiovascular effect of MeHg (see below) (44, 45), but to what
extent these reflect organic or inorganic Hg exposures remains
to be clarified (46). A recent study of women, with no history of
occupational exposure to Hg, showed similar correlations
between Hg intake through fish consumption and both toenail
and hair Hg concentrations; however, only total Hg was
assessed (47). In this study, hair, toenail, and urinary total Hg
were highly correlated. Urinary Hg levels largely reflect
exposure to inorganic Hg (40) and are not considered useful
bioindicators of MeHg exposure. There are, however, several
recent reports of positive correlations between fish consumption
and urinary Hg (48–50), and investigators of these studies
propose that demethylation may account, at least partially, for
this observation. The relation of fish consumption and
inorganic Hg in different biological tissues, and its consequence
for human health still need to be elucidated.
Health effects from low to moderate levels of MeHg
exposure were reported in a variety of systems and domains.
Each of these effects may depend on different aspects of
exposure [e.g., fish-eating patterns, time of exposure (first,
second, or third trimester, childhood, adulthood)]. Therefore,
the different reflections of exposure provided by hair and blood
Hg concentrations may provide different information about
dose-response for different exposure populations and different
exposure scenarios. Few studies investigated side-by-side dose-
response relations for both biomarkers. In the study in the
Faroe Islands, maternal hair and fetal-cord blood predicted
similar but not identical patterns of effect across various
measures of neurologic performance (38).
Fish Consumption as a Predictor of MeHg Exposure
Exposure dose. Although most studies identified a clear
association between the quantity and the frequency of fish
consumption and Hg exposure, there is considerable interindi-
vidual and intergroup variability in the relation between the
amount or the frequency of fish consumption and the levels of
biomarker of MeHg exposure. Several factors mediate this
relation. The MeHg concentration within and across species of
dietary fish is an obvious source of variability. For example,
those who eat mainly carnivorous fish and/or fish-eating
mammals have relatively higher levels of Hg compared with
those who eat mainly noncarnivorous fish (14, 29, 33, 51–54).
Independent of the MeHg concentration, the frequency of fish
consumption is also an important factor in this variability.
Because biomarkers reflect the weighted average of exposure
over time, short-term reporting of fish consumption may not
correspond with a longer-term average of MeHg exposure.
Under some circumstances, episodic exposures can result in
large bolus doses of MeHg. Bolus doses can arise, for example,
from the infrequent consumption of fish or fish-eating
mammals with high concentrations of MeHg. Given practical
limitations in sampling frequency, as well as the nature of some
of the biomarkers themselves, bolus doses during putative
discrete windows of sensitivity in fetal development may not be
fully revealed by biomarkers of exposure.
Toxicokinetics. Although most experimental studies on the
gastrointestinal absorption of MeHg indicated that nearly 100%
of MeHg in fish is absorbed, recently reported animal and
human data suggest that there may be substantial variability
(55, 56). In animal studies, variation in absorption kinetics was
related to factors such as sex and age (57). A further gap exists
because human absorption studies were primarily conducted in
adult male subjects.
Toxicokinetic (pharmacokinetic) models and physiologically
based pharmacokinetic (PBPK) models are applied to estimate
internal dose, given a known intake dose, as well as the intake
dose, given a measured internal dose (38). The basic one-
compartment model (39, 58, 59) is a steady-state model that is
intended to predict concentration in a single compartment only
(generally, blood). As such, it is less flexible than the PBPK
models in predicting nonsteady state conditions and concentra-
tions in other compartments. However, its relative simplicity
has allowed it to be used with probabilistic input parameters to
obtain estimates of population variability in predictions of
blood concentration and intake dose (60). Estimates of concen-
trations in other compartments (e.g., cord blood) can be made
based on empirical ratios relating mercury concentration in
blood to mercury concentrations in those compartments (61).
The PBPK models have the potential to predict changes in
MeHg concentration in various tissues in response to changes in
MeHg intake and in response to physiological changes (e.g.,
pregnancy, growth). They can be used to predict short-term
changes in MeHg concentrations in different compartments
during intake and distribution among compartments, if the
parameters are correct (62–65).
The validity of these models overall is not thoroughly
established under a range of exposures to MeHg by comparison
with actual human data. Although they have the theoretical
advantage of making predictions under dynamic conditions, the
PBPK models are computationally complex and require data on
many parameters whose MeHg-specific values have not been
defined. This lack of MeHg specific values is a major limitation,
particularly for predicting population variability. The extent to
which these models rely on coefficients derived from metabolic
studies and/or physiological parameters obtained in different
populations and subpopulations and studies with other metals/
elements, limits their utility. Nonetheless, both simple toxico-
kinetic models and PBPK models have been used with
reasonable consistency for setting public health guidance.
In humans, there is increasing evidence from environmental
epidemiology studies of ethnic differences in the relation
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between Hg intake from fish consumption and bioindicators of
exposure (56), suggesting that diet and/or metabolic differences
may be influencing mercury uptake and/or excretion. As yet,
such differences have not been investigated in metabolic studies.
Several studies suggest that selenium (Se) may play a role in
MeHg absorption or excretion (66–68), but these data are not
consistent. In the Brazilian Amazon, fruit consumption was
associated with lower hair Hg concentrations (69). A positive
relation was reported between iron and Hg in blood samples
collected from Sweden (70). Overall, little is known about the
factors that may modulate Hg absorption in humans, and
research is needed to better understand this complex issue.
Fetal and infant exposure. One area in which the
toxicokinetic data is consistent is the finding that MeHg is
actively transferred to the fetus across the placenta via neutral
amino acid carriers during gestation (71, 72). Although
maternal and cord blood Hg concentration is highly correlated,
cord blood MeHg is consistently higher than the corresponding
maternal concentration, with an average ratio of about 1.7 (24,
61, 73, 74). Consequently, biomonitoring adult women’s blood
MeHg as a surrogate for potential fetalexposure, the corre-
sponding fetal level will be, on average, 70% higher than
maternal blood and up to three times higher at the 95th
percentile. The maternal body burden of MeHg tends to
decrease during gestation consistent with hemodilution and a
transfer of a portion of the maternal body burden to the fetus
Neonatal and infant exposure to MeHg occurs through
intake of mother’s milk, which is derived from maternal plasma,
has a lower level of MeHg, and is enriched in inorganic Hg
relative to the whole blood (75). Thus, lactational exposure to
MeHg is reduced compared with what would be expected on the
basis of maternal blood MeHg. Human and animal studies
showed that, after birth, there is a decline in MeHg levels,
reaching 40–50% at 2–3 months of age (76–78). During this
period, infant body weight increases about 1.5–2 times.
Consequently, the rapid increase in body volume and the
limited MeHg transfer appear to explain the dilution of MeHg
in infants during breast feeding.
Clinical manifestations. In 1958, McAlpine and Araki (79)
linked the unusual neurological disease that was associated with
fish consumption from Minamata Bay to MeHg exposure. This
historic recognition of the brain and nervous system as the
primary target organ for MeHg poisoning, resulting in marked
distal sensory disturbances, constriction of visual fields, ataxia,
dysarthria, auditory disturbances, and tremor, remains un-
changed (80, 81). Based on analysis of the studies of human
poisoning, the World Health Organization (WHO) (39)
estimated that 5% of MeHg-exposed adults would experience
neurologic effects with a blood Hg level of 200 lg L?1
(corresponding to a hair level of approximately 50 lg g?1).
This estimate, however, was called into question by a re-analysis
of these studies by Kosatsky and Foran (82), who suggested
that the lowest observed effect level for clinical effects is likely to
be considerably lower. Indeed, anecdotal and case reports of
diffuse and subjective neurologic symptoms in adults and older
children with moderately elevated MeHg exposures continue to
appear (36, 83). In many cases, cessation or significant
curtailing of fish consumption results in improvement of
symptoms in conjunction with reduction in biomarker concen-
trations. These suggest the possibility of clinical effects, perhaps
in a sensitive subset of the general population, at levels of
exposure considerably below those previously associated with
clinical effects in poisoning episodes. Currently, there is no
formal case description or diagnostic criteria for such effects.
Although exposures throughout the world are lower than
those producing the historical epidemics of MeHg poisoning,
there is growing evidence that for many populations, exposures
are sufficient to alter normal functioning of several systems,
constitutes an important public health problem.
Effects in neonates, infants, and children. The poisoning in
Minamata brought attention to the risk from fetal exposure.
Exposed to MeHg through the placenta of the exposed mother,
infants showed severe cerebral palsy–like symptoms, even when
their mothers had mild or no manifestation of the poisoning
(84). Mental retardation, cerebellar ataxia, primitive reflexes,
dysarthria, and hyperkinesias were observed. These symptoms,
described over 25 years ago (80, 85), continue as the clinical
hallmark of congenital MeHg poisoning. Reconstruction of
maternal or fetal doses resulting in these symptoms is difficult
because of a lack of concurrent sampling. An estimate of the
mean maternal hair concentration, resulting in such symptoms
of 41lg g?1ppm was proposed (86); however, a large
uncertainty surrounds this estimate. Health effects observed
with frank poisonings should not be confused with the more
subtle, populational effects observed at lower levels of exposure.
At the subclinical and the population level, several studies in
different parts of the world report poorer neurologic status and
slower development in newborns, infants, and/or children
exposed to MeHg in utero and/or during early childhood (87–
98), although some studies did not observe effects (99–101). In
children, MeHg exposure in utero is associated with lower
performance on tests of language, attention, memory, and/or
visuospatial and/or motor functions. Although most child
studies focused on fish-eating populations with relatively high
levels of MeHg exposure, in a recent study, Oken et al (90)
observed an inverse relation between mercury concentration in
maternal hair and infants’ performance on a visual recognition
memory task at levels of mercury exposure consistent with
background exposure in the US population (maternal hair levels
varied between 0.02–2.38 lg g?1). Interestingly, in this study,
fish consumption per se was associated with better performance,
suggesting that some positive aspects of fish consumption,
perhaps n-3 (omega-3) fatty acids, are reduced or antagonized
by the MeHg contained in the same fish. A similar picture is
emerging among adults for the some of the cardiovascular
effects of MeHg (see below).
The two major ongoing longitudinal cohort studies on
children from the Faroe Islands and the Seychelles are worthy
of particular mention because they have both been following
children through teenage years, assessing neuropsychological
performance as a function of current, childhood, and in utero
exposure. The Faroes study consistently observed neurobehav-
ioral deficits associated with in utero exposure, even when
children whose mother’s hair Hg levels above 10 lg g?1were
excluded (91). In the initial studies of the Seychelles cohort, no
effects were observed (100–103). However, recent reports of the
Seychelles 9-year-old cohort shows decreases in fine motor
function associated with higher fetal exposure levels (?10 lg g?1
maternal hair); the investigators suggest that adverse effects
may become apparent on higher-order cognitive functions that
develop with maturity (104, 105). There has been much
discussion about the differences between these two well-
performed studies. Factors such as type of exposure (one of
the main exposure pathways in the Faroes study is through pilot
whale, while in the Seychelles, it is entirely marine fish),
biomarkers of exposure (cord blood vs. maternal hair),
differences in test batteries and age of testing; cohort size and
power were considered as possible explanations for the
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differences in observed outcomes. However, none of these
explanations proved entirely satisfactory or clearly decisive (38,
106). Other hypotheses, such as dietary intake of nutrients that
may modify Hg metabolism or toxicity, were also proposed
(69). Despite whatever significant differences do, in fact, exist
between the Seychelles and Faroes studies that may explain
differences in results that were observed to this time, the most
recent results from the Seychelles appear to indicate a
convergence in findings. More work needs to be done on
factors that may affect the patterns of manifestation of Hg
Neurophysiologic studies offer strong support for nervous-
system alterations associated with MeHg exposure. These
studies showed mercury-related delayed latencies for auditory
and visual evoked potentials (107–110). In the Faroes longitu-
dinal study, latency delays were observed at 7 and 14 years (107,
109). No significant dose-effect relations for evoked potentials
were observed in a study of Japanese children with low mercury
exposure (maternal and children hair mercury levels of 1.6 lg
Nervous system endpoints in adults. Fewer studies addressed
the neurotoxic effects of Hg exposure in adults. Mercury-related
deficits in motor, psychomotor, visual and/or cognitive
functions have been reported for different populations within
the Brazilian Amazon (112–115) and for tuna consumers from
the Mediterranean (116). A recent study, in the United States,
of older adults (50–70 years old) with considerably lower blood
Hg levels (mean, 2.1 lg L?1) showed inconsistent evidence of
effect across neurobehavioral tests (117). Studies of associations
between neurobehavioral outcomes and MeHg exposure in
adult populations in which frequent and lifetime fish consump-
tion is a cultural norm, generally cannot distinguish between
effects because of adult exposure and permanent developmental
effects because of gestational and early childhood exposures.
A body of evidence was developed that addresses potential
associations between MeHg and a range of cardiovascular
effects. These include cardiovascular disease [coronary heart
disease, acute myocardial infarction (AMI), ischemic heart
disease], blood pressure and hypertension effects, and alter-
ations in heart rate variability [see Chan and Egeland (118) and
Stern (119) for recent reviews]. The strongest evidence for causal
associations is for cardiovascular disease, particularly AMI in
adult men (44, 120–122). In general, the relative risk and the
odds ratios for AMI from these studies showed a doubling in
the upper range of the observed Hg exposures. Comparison of
exposures in these studies to exposures in Western populations
suggests that the upper percentiles of current levels of exposure
in these populations may result in a significantly elevated risk of
AMI. Another well-conducted study of US health professionals,
however, did not find an association between Hg exposure and
coronary heart disease (123). This may be because dentists with
possible exposure to elemental mercury accounted for 63% of
controls and had a Hg exposure more than twice that of the
other groups in the cohort. It is not known whether elemental or
inorganic Hg acts similarly to MeHg with respect to cardio-
vascular effects. In addition, two of these studies used toenail
Hg as the biomarker of exposure. Because this biomarker has
not been adequately compared with the more common exposure
biomarkers of hair or blood Hg, it is difficult to assess the dose-
response implications of these studies in relation to current
The evidence for an association between MeHg and other
cardiovascular endpoints is weaker. An association was found
between increased systolic and diastolic blood pressure in
Faroese children at 7 years old and gestational exposure to
MeHg (124). However, the association did not persist when the
cohort was re-examined at 14 years old (125). Decreased heart
rate variability was also associated with MeHg exposure, and
this effect persisted through 14 years of age, but the implications
of this effect in children for clinically significant outcomes is not
clear. There are few studies that relate adult blood pressure to
MeHg exposure. A recent study in the Brazilian Amazon
reported that persons with 10 lg g?1hair Hg were three times
more likely to have elevated systolic blood pressure (?130 mm
Hg) (126), whereas in a study of women from the United States,
no clear association was observed (127).
The effect of MeHg on the sex ratio of offspring at birth and
stillbirth in Minamata City, Japan, in the 1950s and 1960s,
including the period when MeHg pollution was most severe,
showed decreases in male birth in offspring in the overall city
population, among fishing families (72, 128). An increase in the
proportion of male stillborn fetuses raises the possibility that
increased susceptibility of male fetuses to death in utero could
explain the altered sex ratio.
Immune System Effects
Inorganic mercury was shown to suppress immune functions
and to induce autoimmunity in multiple species (129). Both
MeHg and inorganic Hg were shown to produce an autoim-
mune response, as well as an immunosuppressive effect in
several strains of genetically susceptible mice (130, 131).
However, data on the immune effects of MeHg in general are
sparse, and research is required in this area.
Fish tend to accumulate halogenated organics, including
polychlorinated biphenyls (PCB), dioxins, and related com-
pounds. The neurodevelopmental effects of PCBs and, to a
lesser extent, dioxins, share some similarities to those observed
for MeHg (132). This can potentially present difficulties in
determining causality and in constructing MeHg-specific dose-
response relations. Because MeHg tends to associate more with
proteins than with fats, fish species with elevated levels of MeHg
are not necessarily those with elevated levels of the lipophilic
halogenated organics. Thus, for fish consumption where both
exposures occur, the influence of the individual contaminants
can potentially be separated by statistical techniques if a variety
of fish species is consumed and sufficiently precise exposure
metrics are collected. In the Faroe Islands studies, both MeHg
and PCBs appear to jointly affect some developmental
endpoints. However, although MeHg appeared to enhance the
PCB-attributable effects, the PCBs appeared to make a
relatively minor contribution to the MeHg-specific effects
(132, 133). Contradictory findings were observed in a study of
cognitive development associated with exposures to MeHg and
PCBs in the Lake Oswego area of New York State (134). In that
study, elevated PCB exposure appeared to potentiate MeHg
effects. However, both MeHg and PCB levels were considerably
lower than in the Faroes study, and no PCB-MeHg association
was observed on follow-up testing of the cohort. More work
remains to be done on the joint influence of MeHg and
halogenated organics, as well as other metal contaminants that
may also be present in fish (135).
Elemental Hg continues to be used in dental amalgam for the
treatment of dental carries. In populations with significant
amalgam use, elemental Hg may account for a proportion of
total Hg exposure comparable with or greater than MeHg (38).
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It is known that elemental Hg vapor can cross the placenta and
accumulate in fetal tissue (136–138), and animal data suggest
that elemental Hg has the potential to cause adverse neurologic
developmental effects (139). Both elemental Hg and MeHg are
metabolized in the brain to the inorganic mercuric form (38). It
is not known whether the ultimate neurodevelopmental toxicant
of MeHg is MeHg itself, the inorganic mercuric ion, free
radicals generated in the conversion to the inorganic species, or
some combination of these. If the inorganic form is the ultimate
toxicant of MeHg in the developing brain or if MeHg and
inorganic Hg share common neurodevelopmental toxic mech-
anisms, then current estimates of risk based on MeHg exposure
alone could underestimate the population risk. Additional
research is clearly needed to address these questions.
Potential Benefits of Fish Consumption
Several investigators have addressed the issues surrounding the
risks and benefits associated with fish consumption, in general
and for remote communities that depend on fish traditionally
and/or as their dietary mainstay (69, 140–142). Indeed, for
many populations, fish is the primary source of protein and
other nutrients. Moreover, some fish can be an important
source of the omega-3 fatty acids, eicosapentaenoic acid and
docosahexaenoic acid, that appear to have positive effects on at
least some of the same systems adversely affected by MeHg.
However, similar to MeHg, there is considerable variability in
the occurrence of omega-3 fatty acids across species (143). Fatty
fish have higher levels of omega-3s compared with lean fish, and
freshwater fish largely have lower levels of omega-3 fatty acids
compared with ocean fish (15). There is no association between
MeHg concentration of the fish or shellfish species and the
omega-3 fatty acid level of the species (15). Several fish and
shellfish species that are low in MeHg are high in omega-3 fatty
acids (e.g., anchovies, herring, salmon), whereas others that are
high in MeHg can be comparatively low in omega-3 fatty acids
(e.g., shark, swordfish, pike) (15).
Omega-3 fatty acids are associated with beneficial effects on
neurologic development in some studies (15), as has fish
consumption in general, possibly as a correlate of omega-3
intake (90). However, not all studies found such a benefit (15,
144). Omega-3 fatty acids also were linked to a reduction in the
risk of cardiovascular disease (44), although such an association
recently were called into question in a comprehensive review
(145). For both endpoints, there is some evidence suggesting
that, in addition to its intrinsic toxicity, MeHg also antagonizes
the beneficial effects of the omega-3 fatty acids (44, 119, 146).
Because intake of both substances arises from the same food
source, this suggests that the risk-benefit analysis for either the
omega-3s or MeHg will depend on an understanding of this
Some animal studies suggest that micronutrients that are
normally found in high levels in seafood, such as Se and vitamin
E, may protect against Hg toxicity without specifically
modulating MeHg absorption or excretion (55). For Se,
differences across studies in the forms of Se and Hg, and the
route and duration of exposure make interpretation difficult.
Although there is some evidence showing protection against
inorganic Hg toxicity by selenite, there is almost no evidence
showing protection against MeHg toxicity by the organic Se
compounds, such as selenomethione or selenocysteine, that are
the forms of Se commonly found in the human diet. There is no
human data that support a protective role for Se with respect to
Hg neurotoxicity. For vitamin E, there is a suggestion that its
antioxidant properties may protect against some of the adverse
effects of MeHg (147, 148). However, there are few in vivo
studies, and no epidemiological studies have addressed vitamin
RISK ASSESSMENT FOR MeHg
The risk assessment process for chemicals in foods is based on
hazard identification, exposure assessment, dose-response
evaluation, and risk characterization. The most commonly used
paradigms for risk assessment are those reflecting the processes
developed by the National Academy of Sciences/National
Research Council (NAS/NRC) in the United States (149) and
a similar process used internationally by the Joint Expert
Committee on Food Additives and Contaminants (JECFA)
under the Food and Agriculture Organization and the WHO
(150). The NAS/NRC provided recommendations on MeHg in
2000, and JECFA continues to evaluate MeHg after their
evaluation published in WHO Food Additives Series Number
In the risk assessment for MeHg, both NAS\NRC and
JECFA used a benchmark dose approach based on a
predetermined change in response rate of an adverse effect.
Both used the benchmark dose lower limit (BMDL), which is
the statistical lower confidence limit on the dose. Because these
two major risk assessments recommend different intake levels
[0.1 lg kg-body-weight (bw)?1d?1and 0.23 lg kgbw?1d?1,
respectively], here we examine the choices throughout the
process that lead to these differences (Table 1):
i. Choice of study. Currently both rely on neurodevelopment
effects of MeHg as the adverse health effect used in their
respective risk assessments. The NAS/NRC based their
analyses on the Faroes Islands study as the primary source
of epidemiological data and relied on the studies from New
Zealand (87) and the Seychelles as secondary sources and
derived a BMDL, based on cord blood of 58 lg L?1. The
JECFA excluded the New Zealand study and, basing their
BMDL calculation only on the Faroe Islands and the
Seychelles studies, derived a BMDL of 12 lg g?1in maternal
ii. Biomarker of exposure. The NAS/NRC based their analyses
on cord blood, and the JECFA used maternal hair. Because
some of the critical studies for these risk assessments
measured only one of these biomarkers converting between
cord blood and maternal hair concentration (or vice versa)
Table 1. Differences in decision choices between the NAS/NRC (2000) and the JECFA (2003) risk assessments for mercury intake.
VariableNAS/NRC (2000)JECFA (2003)
Studies Considered Faroes, New Zealand, Seychelles.
Final value based on Faroes
Cord blood, lg L?1
58 lg L?1cord blood
Uncertainty factor ¼ 10. 3.2 for toxicokinetics. 3.2 for
Faroes and Seychelles
Biomarker used as index
Maternal hair [Hg], lg g?1or ppm.
14 lg g?1maternal hair
3.2 (100.5) (individual variation) 3 2 for overall average
interindividual variation ¼ 6.4
No toxicodynamic factor.
1.6 lg kgbw?1wk?1(equal to 0.23 lg kgbw?1d?1)
Exposure limitReference dose of 0.1 lg kgbw?1d?1(equal to 0.7 lg
Ambio Vol. 36, No. 1, February 2007
? Royal Swedish Academy of Sciences 2007
involves uncertainty. Furthermore, as the most critical
period(s) of gestation for the neurodevelopmental toxicity
of MeHg are not yet known, it is not clear which lengths of
maternal hair are most appropriate to measure
iii.Uncertainty factor. This factor accounts for adequacy of the
pivotal study, interspecies extrapolation, interindividual
variability in humans, adequacy of the overall data base,
and the nature of the toxicity. These are not ‘‘safety factors’’
in that they are intended to factor in quantitatively to
address areas of uncertainty in the risk assessment rather
than provide ‘‘safety’’ per se. The magnitude of the
uncertainty factors is intended as an estimate of the influence
of these uncertainties, rather than the application of an
arbitrary layer of safety. In the assessment conducted by the
NAS/NRC committee, a composite uncertainty factor of 10
was used to account for variability and uncertainty in
toxicokinetics and toxicodynamic, as well as database
insufficiency for endpoints possibly more sensitive than
neurodevelopmental (e.g., cardiovascular endpoints). The
JECFA used an overall uncertainty factor of 6.4 to address
variability in both toxicokinetics and toxicodynamics. The
toxicokinetic portion accounts for a factor of 3.2 based on a
generalized estimate of intraspecies toxicokinetic variability
(152). The toxicodynamic portion likewise accounts for a
factor of 2.0 based on a generalized estimate of interindi-
vidual variability in response.
The starting points for derivation of their respective
recommended intakes differ both with respect to the actual
values and the approaches taken. The JECFA Committee
estimated that a steady-state intake of 1.5 lg kgbw?1d?1would
be an exposure that would have no appreciable adverse effects
on children, in contrast to the NAS/NRC determination of a
BMDL of 1.0 lg kgbw?1d?1, which is an effect level. However,
neither of these assessments reflected bioconcentration of
MeHg across the placental circulation from the mother to the
fetus (61). This bioconcentration and its population variability
suggests that the full toxicokinetic variability is significantly
larger (60, 153) than previously estimated (38, 151, 154).
The NAS/NRC used cord blood mercury for their BMDL of
58 lg L?1, as did the US Environmental Protection Agency in
2001. However, the subsequent increased recognition that cord
blood mercury is, on average, 60% to 70% higher in Hg than
maternal blood, coupled to the coefficient of variation around
the mid-point of 1.7 described by Stern and Smith (61) as 0.56
with a 95th percentile of 3.4, supports the use of a blood
mercury concentration in the mid-30 lg L?1range to recognize
this fetal-maternal blood mercury difference (152, 155). By
contrast, assessments based on association of maternal hair Hg
with adverse neurobehavioral outcomes in the child after in
utero exposures to MeHg need no such adjustment for MeHg
PANEL CONSENSUS CONCLUSIONS
Methylmercury is a potent toxicant, bioaccumulated and
concentrated through the aquatic food chain, placing at risk
humans who consume high-end aquatic predators or for whom
fish is a dietary mainstay. Elevated levels of MeHg exposure
occur worldwide and are not restricted to isolated populations.
Rather, exposure to MeHg at levels above those that can be
considered clearly safe and without risk of adverse effect occur
throughout the globe and across the socioeconomic spectrum.
Hair and blood Hg concentrations (including cord blood Hg
concentrations) are valid biomarkers of MeHg exposure. Each
conveys somewhat different information on exposure. The most
useful picture of exposure is likely to be obtained by data from
both biomarkers, along with specific dietary information on fish
consumption and other dietary data. Urinary Hg concentration
is a biomarker of inorganic Hg. More research characterizing
the relations between toenail Hg, hair Hg, blood Hg, and
urinary Hg, and the relations between MeHg and inorganic Hg
should be considered a priority. Single-strand and, particularly,
continuous single-strand hair analysis of Hg concentration
should be pursued as the best method for elucidating dynamic
changes in MeHg exposure. This is particularly relevant for
studies of the effect of in utero exposure to MeHg to assess the
significance of bolus doses.
Total fish consumption without differentiating fish species is
not necessarily a dependable metric for estimating MeHg
exposure. To be useful for such purposes, valid data on the
MeHg concentration of each species, as well as the frequency
and the amount of consumption for each species must be
There is sufficient evidence to state that MeHg is a
developmental neurotoxin, and developmental or fetal neuro-
toxicity has constituted the basis for risk assessments and public
health policies. Although uncertainties in the risk assessment for
the neurodevelopmental effects of MeHg remain, there is
sufficient evidence to warrant a public health response based
on prudent selection of fish species in the diet. Development of a
formal case description and diagnostic criteria for the clinical
effects of MeHg observed in some adults and older children
with moderately elevated MeHg exposure should be a priority
for clinicians involved with MeHg research.
Current studies suggest that present levels of exposure to
MeHg have the potential to result in an elevated risk of
cardiovascular disease to a significant fraction of the popula-
tion. However, additional studies in other populations would
clarify this picture. Quantitative dose-response assessment of
existing studies should be undertaken. The potential effect of
MeHg on the immune system should be investigated with
respect to adverse effects on immune response, as well as with
respect to individual sensitivities to MeHg, potentially including
To date, it has been possible to statistically separate the
neurodevelopmental effects of MeHg and PCBs in key studies
where both exposures occur in the fish-consuming population.
However, knowledge of the mechanisms and interactions of
PCBs and other halogenated organics with MeHg is an
important missing piece in understanding the overall risk for
fish consumption. Research into the potential interactions of
inorganic Hg and MeHg should be considered a priority.
Although the possible interactions between Se and MeHg are a
fruitful area for further research, there is currently no clear
evidence that dietary Se can modulate the toxicity of MeHg.
Because the intake of both omega-3 fatty acids and MeHg
occurs from fish consumption and because MeHg appears to
antagonize the beneficial effects of the omega-3s as well as
exerting its own intrinsic toxicity, a proper assessment of risks
and benefits for the combination of the two must address their
complex interaction. Currently, there are insufficient data on
this interaction to describe a coherent picture. Despite the lack
of a clear picture of the interaction of the omega-3 fatty acids
and MeHg, there are fish with high levels of omega-3s and
relatively low levels of MeHg. Consumption of fish with low
levels of MeHg and organic contaminants constitute a ‘‘win-
win’’ situation and should be encouraged regardless of the
underlying nature of the omega-3-MeHg interaction.
To preserve human health, all efforts need to be made to
reduce and eliminate sources of exposure, through regulation
and dissemination of information. In addition to documenting
the multiple health hazards associated with exposure to MeHg
throughout the lifespan, research needs to focus on identifying
factors that influence the uptake and the toxicity of MeHg and
Ambio Vol. 36, No. 1, February 2007
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on examining the potential benefits of different fish species.
These studies will provide information on maximizing nutri-
tional intake from consumption and minimizing risk from
exposure to MeHg.
References and Notes
1.Clarkson, T.W. 2002. The three modern faces of mercury. Environ. Health Perspect.
110 (Suppl 1), 11–23.
Counter, S.A., Buchanan, L.H. and Ortega, F. 2005. Mercury levels in urine and hair
of children in an Andean gold-mining settlement. Int. J. Occup. Environ. Health. 11,
United Nations Environment Programme (UNEP). December 2002. Global Mercury
Assessment. UNEP Chemicals, Geneva. (http://new.unep.org/civil_society/GCSF8/
pdfs/mercury_ass_rep_eng.pdf) Accessed 1/5/07.
Ventura, D.F., Costa, M.T., Costa, M.F., Berezovsky, A., Salomao, S.R., Simoes,
A.L., Lago, M., Pereira, L.H. et al. 2004. Multifocal and full-field electroretinogram
changes associated with color-vision loss in mercury vapor exposure. Vis. Neurosci. 21
Drake, P.L., Rojas, M., Reh, C.M., Mueller, C.A. and Jenkins, F.M. 2001.
Occupational exposure to airborne mercury during gold mining operations near El
Callao, Venezuela. Int. Arch. Occup. Environ. Health. 74, 206–212.
Keating, M.H., Mahaffey, K.R., Schoeny, R., Rice, G.E., Bullock, O.R., Ambrose,
R.B., Swartout, J. and Nichols, J.W. 1997. Mercury Sudy Report to Congress, Vol. III:
Fate and Transport of Mercury in the Environment. Office of Air Quality Planning and
Standards and Office of Research and Development, U.S. Environmental Protection
Agency, EPA-452/R-97–005. EPA, Washington, D.C.
Choi, M.H. and Cech, J.J. 1998 Unexpectedly high mercury level in pelleted
commercial fish feed. Environ. Toxicol. Chem. 17, 1979–1981.
Easton, M.D.L., Luszniak, D. and Von der Geest, E. 2002. Preliminary examination of
contaminant loadings in farmed salmon, wild salmon and commercial salmon feed.
Chemosphere 46, 1053–1074.
Foran, J.A., Hites, R.A., Carpenter, D.O., Hamilton, M.C., Mathews-Amos, A. and
Schwager, S.J. 2004. A survey of metals in tissues of farmed atlantic and wild pacific
salmon. Environ. Toxicol. Chem. 23, 2108–2110.
Horvat, M., Nolde, N., Fajon, V., Jereb, V., Logar, M., Lojen, S., Jacimovic, R.,
Falnoga, I. et al. 2003. Total mercury methylmercury and selenium in mercury polluted
areas in the province Guizhou, China. Sci. Total Environ. 304, 231–256.
Ysart, G., Miller, P., Croasdale, M., Crews, H., Robb, P., Baxter, M., de L’Argy, C.
and Harrison, N. 2000. 1997 UK Total Diet Study—dietary exposures to aluminium,
arsenic, cadmium, chromium, copper, lead, mercury, nickel, selenium, tin, and zinc.
Food Addit. Contam. 17, 775–786.
Lindberg, A., Bjornberg, K.A., Vahter, M. and Berglund, M. 2004. Exposure to
methylmercury in non-fish-eating people in Sweden. Environ. Res. 96, 28–33.
Grandjean, P., Weihe, P., Needham, L.L., Burse, V.W., Patterson, D.G. Jr, Sampson,
E.J., Jorgensen, P.J. and Vahter, M. 1995. Relation of a seafood diet to mercury,
selenium, arsenic, and polychlorinated biphenyl and other organochlorine concentra-
tions in human milk. Environ. Res. 71, 29–38.
Van Oostdam, J., Donaldson, S.G., Feeley, M., Arnold, D., Ayotte, P., Bondy, G.,
Chan, L., Dewaily, E. et al. 2005. Human health implications of environmental
contaminants in Arctic Canada: a review. Sci. Total. Environ. 351–352 165–246.
Mahaffey, K.R., Clickner, R.P. and Bodurow, C.C. 2004. Blood organic mercury and
dietary mercury intake: National Health and Nutrition Examination Survey, 1999 and
2000. Environ. Health Perspect. 112, 562–70.
McDowell, M.A., Dillon, C.F., Osterloh, J., Bolger, P.M., Pellizzari, E., Fernando, R.,
de Oca, R.M., Schober, S.E. et al. 2004. Hair mercury levels in US children and women
of childbearing age: reference range data from NHANES 1999–2000. Environ. Health
Perspect. 112 1165–1171.
Becker, K., Kaus, S., Krause, C., Lepom, P., Schulz, C., Seiwert, M. and Seifert, B.
2002. German Environmental Survey 1998 (GerES III): environmental pollutants in
blood of the German population. Int. J. Hyg. Environ. Health. 205, 297–308.
Yasutake, A., Matsumoto, M., Yamaguchi, M. and Hachiya, N. 2004. Current hair
mercury levels in Japanese for estimation of methylmercury exposure J. Health Sci. 50,
Pirrone, N. and Mahaffey, K.R. (eds) 2005. Dynamics of Mercury Pollution on Regional
and Global Scales: Atmospheric Processes and Human Exposures Around the World.
Springer-Verlag, New York, 748 pp.
Stern, A.H., Gochfeld, M., Weisel, C. and Burger, J. 2001. Mercury and methylmercury
exposure in the New Jersey pregnant population. Arch. Environ. Health. 56, 4–10.
Knobeloch, L., Anderson, H.A., Imm, P., Peters, D. and Smith, A. 2005. Fish
consumption, advisory awareness, and hair mercury levels among women of
childbearing age. Environ. Res. 97, 220–227.
Bjornberg, K.A., Vahter, M., Petersson-Grawe, K., Glynn, A., Cnattingius, S.,
Darnerud, P.O., Atuma, S., Aune, M. et al. 2003. Methyl mercury and inorganic
mercury in Swedish pregnant women and in cord blood: influence of fish consumption.
Environ. Health Perspect. 111 637–641.
Pesch, A., Wilhelm, M., Rostek, U., Schmitz, N., Weishoff-Houben, M., Ranft, U. and
Idel, H. 2002. Mercury concentrations in urine, scalp hair, and saliva in children from
Germany. J. Expo. Anal. Environ. Epidemiol. 12, 252–258.
Morrissette, J., Takser, L., St-Amour, G., Smargiassi, A., Lafond, J. and Mergler, D.
2004. Temporal variation of blood and hair mercury levels in pregnancy in relation to
fish consumption history in a population living along the St. Lawrence River. Environ.
Res. 95, 363–374.
Legrand, M., Arp, P., Ritchie, C. and Chan, H.M. 2005. Mercury exposure in two
coastal communities of the Bay of Fundy, Canada. Environ. Res. 98, 14–21.
Schober, S.E., Sinks, T.H., Jones, R.L., Bolger, P.M., McDowell, M., Osterloh, J.,
Garrett, E.S., Canady, R.A. et al. 2003. Blood mercury levels in US children and
women of childbearing age 1999–2000. J. Am. Med. Assoc. 289, 1667–1674
Grandjean, P., Weihe, P., Jorgensen, P.J., Clarkson, T., Cernchiari, E. and Videro, T.
1992. Impact of maternal seafood diet on fetal exposure to mercury, selenium and lead.
Arch. Environ. Health. 47, 185–195.
Cernichiari, E., Brewer, R., Myers, G.J., Marsh, D.O., Lapham, L.W., Cox, C.,
Shamlaye, C.F., Berlin, M. et al. 1995. Monitoring methylmercury during pregnancy:
maternal hair predicts fetal brain exposure. Neurotoxicology. 16 711–716.
Lebel, J., Roulet, M., Mergler, D., Lucotte, M. and Larribe, F. 1997. Fish diet and
mercury exposure in a riparian Amazonian population. Water Air Soil Pollut. 97,
Santos, E.C., Camara, V.M., Jesus, I.M., Brabo, E.S., Loureiro, E.C., Mascarenhas,
A.F., Fayal, K.F., Sa Filho, G.C. et al. 2002. A contribution to the establishment of
reference values for total mercury levels in hair and fish in Amazonia. Environ. Res. 90
31. Santos, E.C., Jesus, I.M., Brabo, E.S., Loureiro, E.C., Mascarenhas, A.F., Weirich, J.,
Camara, V.M. and Cleary, D. 2000. Mercury exposures in riverside Amazon
communities in Para, Brazil. Environ. Res. 84, 100–107.
Boischio, A.A. and Henshel, D.S. 2000. Linear regression models of methyl mercury
exposure during prenatal and early postnatal life among riverside people along the
upper Madeira river, Amazon. Environ. Res. 83, 150–161.
Dolbec, J., Mergler, D., Larribe, F., Roulet, M., Lebel, J. and Lucotte, M. 2001.
Sequential analysis of hair mercury levels in relation to fish diet of an Amazonian
population, Brazil. Sci. Total Environ. 27, 87–97.
Dorea, J., Barbosa, A.C., Ferrari, I. and de Souza, J.R. 2003. Mercury in hair and in
fish consumed by riparian women of the Rio Negro, Amazon, Brazil. 2003. Int. J.
Environ. Health Res. 13, 239–248.
Burger, J. and Gochfeld, M. 2004. Mercury in canned tuna: white versus light and
temporal variation. Environ. Res. 96, 239–249.
Hightower, J.M. and Moore, D. 2003. Mercury levels in high-end consumers of fish.
Environ. Health Perspect. 111, 604–608.
Saint-Phard, D. and Van Dorsten, B. 2004. Mercury toxicity: clinical presentations in
musculoskeletal medicine. Orthopedics 27, 394–397.
U.S. National Research Council (U.S. NRC). 2000. Toxicological Effects of
Methylmercury. National Academy Press, Washington, DC, 344 pp.
WHO. 1990. Methylmercury. Environmental Health Criteria 101. World Health
Organization, International Programme on Chemical Safety, Geneva, Switzerland.
Berglund, M., Lind, B., Bjornberg, K.A., Palm, B., Einarsson, O. and Vahter, M. 2005
Inter-individual variations of human mercury exposure biomarkers: a cross-sectional
assessment. Environ. Health 4, 20.
Budtz-Jorgensen, E., Grandjean, P., Jorgensen, P.J., Weihe, P. and Keiding, N. 2004.
Association between mercury concentrations in blood and hair in methylmercury-
exposed subjects at different ages. Environ. Res. 95, 385–393.
Legrand, M., Passos, C.J., Mergler, D. and Chan, H.M. 2005. Biomonitoring of
mercury exposure with single human hair strand. Environ. Sci. Technol. 39, 4594–4598.
Legrand, M., Lam, R., Jensen-Fontaine, M., Salin, E.D. and Chan, H.M. 2004.
Direct detection of mercury in single human hair strands by laser ablation induct
ively coupled plasma mass spectrometry (LA-ICP-MS). J. Anal. At. Spectrom. 19,
Guallar, E., Sanz-Gallardo, M.I., van’t Veer, P., Bode, P., Aro, A., Gomez-Aracena, J.,
Kark, J.D., Riemersma, R.A. et al. 2002. Heavy Metals and Myocardial Infarction
Study Group. Mercury fish oils, and the risk of myocardial infarction. N. Engl. J. Med.
Wickre, J.B., Folt, C.L., Sturup, S. and Karagas, M.R. 2004. Environmental exposure
and fingernail analysis of arsenic and mercury in children and adults in a Nicaraguan
gold mining community. Arch. Environ. Health 59, 400–409.
Morton, J., Mason, H.J., Ritchie, K.A. and White, M. 2004. Comparison of hair, nails
and urine for biological monitoring of low level inorganic mercury exposure in dental
workers. Biomarkers 9, 47–55.
Ohno, T., Sakamoto, M., Kurosawa, T., Dakeishi, M., Iwata, T. and Murata, K. 2006.
Total mercury levels in hair, toenail and urine among women free from occupational
exposure and their relations to tubular renal function. Environ. Res. (e-pub ahead of
print) (In press).
Carta, P., Flore, C., Alinovi, R., Ibba, A., Tocco, M.G., Aru, G., Carta, R., Girei, E. et
al. 2003. Sub-clinical neurobehavioral abnormalities associated with low level of
mercury exposure through fish consumption. Neurotoxicology 24 617–623.
Levy, M., Schwartz, S., Dijak, M., Weber, J.P., Tardif, R. and Rouah, F. 2004.
Childhood urine mercury excretion: dental amalgam and fish consumption as exposure
factors. Environ. Res. 94, 283–290.
Johnsson, C., Schutz, A. and Sallsten, G. 2005. Impact of consumption of freshwater
fish on mercury levels in hair, blood, urine, and alveolar air. J. Toxicol. Environ. Health
Part A. 68, 129–140.
Johnsson, C., Sallsten, G., Schutz, A., Sjors, A. and Barregard, L. 2004. Hair mercury
levels versus freshwater fish consumption in household members of Swedish angling
societies. Environ. Res. 96, 257–263.
Kosatsky, T., Przybysz, R. and Armstrong, B. 2000. Mercury exposure in Montrealers
who eat St. Lawrence River sportfish. Environ. Res. 84, 36–43.
Chan, H.M. and Receveur, O. 2000. Mercury in the traditional diet of indigenous
peoples in Canada. Environ. Pollut. 110, 1–2.
Muckle, G., Ayotte, P., Dewailly, E., Jacobson, S.W. and Jacobson, J.L. 2001.
Determinants of polychlorinated biphenyls and methylmercury exposure in Inuit
women of childbearing age. Environ. Health Perspect. 109, 957–963.
Chapman, L. and Chan, H.M. 2000. The influence of nutrition on methyl mercury
intoxication. Environ. Health Perspect. 108 (Suppl 1), 29–56.
Canuel, R., de Grosbois, S.B., Atikesse, L., Lucotte, M., Arp, P., Ritchie, C., Mergler,
D., Chan, H.M. et al. 2006. New evidence on variations of human body burden of
methylmercury from fish consumption. Environ. Health Perspect. 114 302–306.
Clarkson, T.W. 1997. The toxicology of mercury. Crit. Rev. Clin. Lab. Sci. 34, 369–403.
Smith, J.C., Allen, P.V., Turner, M.D., Most, B., Fisher, H.L. and Hall, L.L. 1994. The
kinetics of intravenously administered methyl mercury in man. Toxicol. Appl.
Pharmacol. 128, 251–256.
Smith, J.C. and Farris, F.F. 1996. Methyl mercury pharmacokinetics in man: a
reevaluation. Toxicol. Appl. Pharmacol. 137, 245–252.
Stern, A.H. 2005. A revised probabilistic estimate of the maternal methyl mercury
intake dose corresponding to a measured cord blood mercury concentration. Environ.
Health Perspect. 113, 155–163.
Stern, A.H. and Smith, A.E. 2003. An assessment of the cord blood:maternal blood
methylmercury ratio: implications for risk assessment. Environ. Health Perspect. 111,
O’Flaherty, E.J. 1998. Physiologically based models of metal kinetics. Crit. Rev.
Toxicol. 28, 271–317.
Clewell, H.J., Gearhart, J.M., Gentry, P.R., Covington, T.R., Van Landingham, C.B.,
Crump, K.S. and Shipp, A.M. 1999. Evaluation of the uncertainty in an oral reference
dose for methylmercury due to interindividual variability in pharmacokinetics. Risk
Anal. 19, 547–558.
Carrier, G., Bouchard, M., Brunet, R.C. and Caza, M. 2001. A toxicokinetic model for
predicting the tissue distribution and elimination of organic and inorganic mercury
following exposure to methyl mercury in animals and humans. II. Application and
validation of the model in humans. Toxicol. Appl. Pharmacol. 171, 50–60.
Young, J.F., Wosilait, W.D. and Luecke, R.H. 2001. Analysis of methylmercury
disposition in humans utilizing a PBPK model and animal pharmacokinetic data. J.
Toxicol. Environ. Health A. 63, 19–52.
Lemire, M., Mergler, D., Fillion, M., Passos, C.J., Guimaraes, J.R., Davidson, R. and
Lucotte, M. 2006. Elevated blood selenium levels in the Brazilian Amazon. Sci. Total
Environ. 366, 101–111.
Barany, E., Bergdahl, I.A., Bratteby, L.E., Lundh, T., Samuelson, G., Skerfving, S.
and Oskarsson, A. 2003. Mercury and selenium in whole blood and serum in relation to
fish consumption and amalgam fillings in adolescents. J. Trace Elem. Med. Biol. 17,
Ambio Vol. 36, No. 1, February 2007
? Royal Swedish Academy of Sciences 2007
68.Chen, C., Yu, H., Zhao, J., Li, B., Qu, L., Liu, S., Zhang, P. and Chai, Z. 2006. The
roles of serum selenium and selenoproteins on mercury toxicity in environmental and
occupational exposure. Environ. Health Perspect. 114, 297–301.
Passos, C.J., Mergler, D., Gaspar, E., Morais, S., Lucotte, M., Larribe, F., Davidson,
R. and de Grosbois, S. 2003. Eating tropical fruit reduces mercury exposure from fish
consumption in the Brazilian Amazon. Environ. Res. 93, 123–130.
Barany, E., Bergdahl, I.A., Bratteby, L.E., Lundh, T., Samuelson, G., Skerfving, S. and
Oskarsson, A. 2005. Iron status influences trace element levels in human blood and
serum. Environ. Res. 98, 215–223.
Kajiwara, Y., Yasutake, A., Adachi, T. and Hirayama, K. 1996. Methylmercury
transport across the placenta via neutral amino acid carrier. Arch. Toxicol. 70, 310–314.
Sakamoto, M., Nakano, A. and Akagi, H. 2001. Declining Minamata male birth ratio
associated with increased male fetal death due to heavy methylmercury pollution.
Environ. Res. 87, 92–98.
Butler Walker, J., Louseman, J., Seddon, I., McMullen, E., Tofflemire, K., Mills, C.,
Corriveau, A., Weber, J.P. et al. 2006. Maternal and umbilical cord blood levels of
mercury lead, cadmium, and essential trace elements in Arctic Canada. Environ. Res.
Sakamoto, M., Kubota, M., Liu, X.J., Murata, K., Nakai, K. and Satoh, H. 2004.
Maternal and fetal mercury and n-3 polyunsaturated fatty acids as a risk and benefit of
fish consumption to fetus. Environ. Sci. Technol. 38, 3860–3863.
Oskarsson, A., Schultz, A., Skerfving, S., Hallen, I.P., Ohlin, B. and Lagerkvist, B.J.
1996. Total and inorganic mercury in breast milk in relation to fish consumption and
amalgam in lactating women. Arch. Environ. Health 51, 234–241.
Sandborgh-Englund, G., Ask, K., Belfrage, E. and Ekstrand, J. 2002. Evaluation of
changes in methylmercury accumulation in the developing rat brain and its effects: a
study with consecutive and moderate dose exposure throughout gestation and lactation
periods. Brain Res. 949, 43–50.
Bjornberg, K.A., Vahter, M., Berglund, B., Niklasson, B., Blennow, M. and
Sandborgh-Englund, G. 2005. Transport of methylmercury and inorganic mercury to
the fetus and breast-fed infant. Environ. Health Perspect. 113, 1381–1385.
Sakamoto, M., Kakita, A., Wakabayashi, K., Nakano, A., Takahashi, H. and Akagi,
H. 2001. Evaluation of changes in methylmercury accumulation in the developing rat
brain and its effects: a study with consecutive and moderate dose exposure through
gestation and lactation periods. Brain Res. 949, 51–59.
McAlpine, D. and Araki, S. 1958. Minamata disease. An unusual neurological disorder
caused by contaminated fish. Lancet 2, 629–631.
Harada, M. 1995. Minamata disease: methylmercury poisoning in Japan caused by
environmental pollution. Crit. Rev. Toxicol. 25, 1–24.
Clarkson, T.W., Magos, L. and Myers, G.J. 2003. The toxicology of mercury—current
exposures and clinical manifestations. N. Engl. J. Med. 349, 1731–1737.
Kosatsky, T. and Foran, P. 1996. Do historic studies of fish consumers support the
widely accepted LOEL for methylmercury in adults. Neurotoxicology. 17, 177–186.
Knobeloch, L., Steenport, D., Schrank, C. and Anderson, H. 2006. Methylmercury
exposure in Wisconsin: a case study series. Environ. Res. 101, 113–122.
Harada, M. 1978. Congenital Minamata disease: intrauterine methylmercury
poisoning. Teratology 18, 285–288.
Marsh, D.O., Myers, G.J., Clarkson, T.W., Amin-Zaki, L., Tikriti, S. and Majeed,
M.A. 1980. Fetal methylmercury poisoning: clinical and toxicological data on 29 cases.
Ann. Neurol. 7, 348–353.
Akagi, H., Grandjean, P., Takizawa, Y. and Weihe, P. 1998. Methylmercury dose
estimation from umbilical cord concentrations in patients with Minamata disease.
Environ. Res. 77, 98–103.
Crump, K.S., Kjellstrom, T., Shipp, A.M., Silvers, A. and Stewart, A. 1998. Influence
of prenatal mercury exposure upon scholastic and psychological test performance:
benchmark analysis of a New Zealand cohort. Risk Anal. 18, 701–713.
Steuerwald, U., Weihe, P., Jorgensen, P.J., Bjerve, K., Brock, J., Heinzow, B., Budtz-
Jorgensen, E. and Grandjean, P. 2000. Maternal seafood diet, methylmercury exposure,
and neonatal neurologic function. J. Pediatr. 136, 599–605.
Grandjean, P., White, R.F., Weihe, P. and Jorgensen, P.J. 2003. Neurotoxic risk caused
by stable and variable exposure to methylmercury from seafood. Ambul. Pediatr. 3,
Oken, E., Wright, R.O., Kleinman, K.P., Bellinger, D., Amarasiriwardena, C.J.,
Hu, H., Rich-Edwards, J.W. and Gillman, M.W. 2005 Maternal fish consumption,
hair mercury, and infant cognition in a U.S. Cohort. Environ. Health Perspect. 113,
Grandjean, P., Weihe, P., White, R.F., Debes, F., Araki, S., Yokoyama, K., Murata,
K., Sorensen, N. et al. 1997. Cognitive deficit in 7-year-old children with prenatal
exposure to methylmercury. Neurotoxicol. Teratol. 19, 417–428.
Cordier, S., Garel, M., Mandereau, L., Morcel, H., Doineau, P., Gosme-Seguret, S.,
Josse, D., White, R. et al. 2002. Neurodevelopmental investigations among
methylmercury-exposed children in French Guiana. Environ. Res. 89 1–11.
Grandjean, P., White, R.F., Nielsen, A., Cleary, D. and de Oliveira Santos, E.C. 1999.
Methylmercury neurotoxicity in Amazonian children downstream from gold mining.
Environ. Health Perspect. 107, 587–591.
Grandjean, P., Weihe, P., White, R.F. and Debes, F. 1998. Cognitive performance
of children prenatally exposed to ‘‘safe’’ levels of methylmercury. Environ. Res. 77,
Weihe, P., Hansen, J.C., Murata, K., Debes, F., Jorgensen, P., Steuerwald, U., White,
R.F. and Grandjean, P. 2002. Neurobehavioral performance of Inuit children with
increased prenatal exposure to methylmercury. Int. J. Circumpolar. Health. 61, 41–49.
Despres, C., Beuter, A., Richer, F., Poitras, K., Veilleux, A., Ayotte, P., Dewailly, E.,
Saint-Amour, D. et al. 2005. Neuromotor functions in Inuit preschool children exposed
to Pb PCBs, and Hg. Neurotoxicol. Teratol. 27, 245–257.
Jedrychowski, W., Jankowski, J., Flak, E., Skarupa, A., Mroz, E., Sochacka-Tatara,
E., Lisowska-Miszczyk, I., Szpanowska-Wohn, A. et al. 2006. Effects of prenatal
exposure to mercury on cognitive and psychomotor function in one-year-old infants:
epidemiologic cohort study in Poland. Ann. Epidemiol. 16, 439–447.
Fabio Barbone, F., Valent, F., Pisa1, F., Daris, F., Fajon, V., Gibicar, D., Logar, M.
and Horvat, M. 2004. Prenatal low-level methyl mercury exposure and child
development in an Italian coastal area. Seychelles Medical and Dental Journal. 7,
Grandjean, P., Weihe, P. and White, R.F. 1995. Milestone development in infants
exposed to methylmercury from human milk. Neurotoxicology. 16, 27–33.
Myers, G.J., Davidson, P.W., Shamlaye, C.F., Axtell, C.D., Cernichiari, E., Choisy, O.,
Choi, A., Cox, C. et al. 1997. Effects of prenatal methylmercury exposure from a high
fish diet on developmental milestones in the Seychelles Child Development Study.
Neurotoxicology 18, 819–829.
Myers, G.J., Davidson, P.W., Cox, C., Shamlaye, C.F., Palumbo, D., Cernichiari, E.,
Sloane-Reeves, J., Wilding, G.E. et al. 2003. Prenatal methylmercury exposure from
ocean fish consumption in the Seychelles child development study. Lancet. 361,
Davidson, P.W., Myers, G.J., Cox, C., Axtell, C., Shamlaye, C., Sloane-Reeves, J.,
Cernichiari, E., Needham, L. et al. 1998 Effects of prenatal and postnatal
methylmercury exposure from fish consumption on neurodevelopment: outcomes at
66 months of age in the Seychelles Child Development Study. J. Am. Med. Assoc. 280,
Davidson, P.W., Myers, G.J., Shamlaye, C., Cox, C., Gao, P., Axtell, C., Morris, D.,
Sloane-Reeves, J., Cernichiari, E., Choi, A., Palumbo, D. and Clarkson, T.W. 1999.
Association between prenatal exposure to methylmercury and developmental outcomes
in Seychellois children: Effect modification by social and environmental factors.
Neurotoxicology 20, 833–841.
Davidson, P.W., Myers, G.J., Weiss, B., Shamlaye, C.F. and Cox, C. 2006. Prenatal
methyl mercury exposure from fish consumption and child development: a review of
evidence and perspectives from the Seychelles Child Development Study. Neurotox-
icology 27, 1106–1109.
van Wijngaarden, E., Beck, C., Shamlaye, C.F., Cernichiari, E., Davidson, P.W.,
Myers, G.J. and Clarkson, T.W. 2006. Benchmark concentrations for methyl mercury
obtained from the 9-year follow-up of the Seychelles Child Development Study.
Neurotoxicology 27, 702–709.
Stern, A.H., Jacobson, J.L., Ryan, L. and Burke, T.A. 2004. Do recent data from the
Seychelles Islands alter the conclusions of the NRC Report on the toxicological effects
of methylmercury? Environ. Health 3, 2.
Murata, K., Weihe, P., Renzoni, A., Debes, F., Vasconcelos, R., Zino, F., Araki, S.,
Jorgensen, P.J. et al. 1999. Delayed evoked potentials in children exposed to
methylmercury from seafood. Neurotoxicol. Teratol. 21 343–348.
Murata, K., Budtz-Jorgensen, E. and Grandjean, P. 2002. Benchmark dose calculations
for methylmercury-associated delays on evoked potential latencies in two cohorts of
children. Risk Anal. 22, 465–474.
Murata, K., Weihe, P., Budtz-Jorgensen, E., Jorgensen, P.J. and Grandjean, P. 2004.
Delayed brainstem auditory evoked potential latencies in 14-year-old children exposed
to methylmercury. J. Pediatr. 144, 177–183.
Saint-Amour, D., Roy, M.S., Bastien, C., Ayotte, P., Dewailly, E., Despres, C.,
Gingras, S. and Muckle, G. 2006. Alterations of visual evoked potentials in preschool
Inuit children exposed to methylmercury and polychlorinated biphenyls from a marine
diet. Neurotoxicology 27, 267–278.
Murata, K., Sakamoto, M., Nakai, K., Weihe, P., Dakeishi, M., Iwata, T., Liu, X.J.
and Ohno, T. et al. 2004. Effects of methylmercury on neurodevelopment in Japanese
children in relation to the Madeiran study. Int. Arch. Occup. Environ. Health 77,
Lebel, J., Mergler, D., Lucotte, M., Amorim, M., Dolbec, J., Miranda, D., Arantes,
G., Rheault, I. et al. 1996. Evidence of early nervous system dysfunction in Amazonian
populations exposed to low-levels of methylmercury. Neurotoxicology 17 157–167.
Lebel, J., Mergler, D., Branches, F., Lucotte, M., Amorim, M., Larribe, F. and Dolbec,
J. 1998. Neurotoxic effects of low-level methylmercury contamination in the
Amazonian Basin. Environ. Res. 79, 20–32.
Dolbec, J., Mergler, D., Sousa Passos, C.J., Sousa de Morais, S. and Lebel, J. 2000.
Methylmercury exposure affects motor performance of a riverine population of the
Tapajos river, Brazilian Amazon. Int. Arch. Occup. Environ. Health. 73, 195–203.
Yokoo, E.M., Valente, J.G., Grattan, L., Schmidt, S.L., Platt, I. and Silbergeld, E.K.
2003. Low level methylmercury exposure affects neuropsychological function in adults.
Environ. Health 2, 8.
Carta, P., Flore, C., Alinovi, R., Ibba, A., Tocco, M.G., Aru, G., Carta, R., Girei, E. et
al. 2003. Sub-clinical neurobehavioral abnormalities associated with low level of
mercury exposure through fish consumption. Neurotoxicology. 24 617–623.
Weil, M., Bressler, J., Parsons, P., Bolla, K., Glass, T. and Schwartz, B. 2005. Blood
mercury levels and neurobehavioral function. J. Am. Med. Assoc. 293, 1875–1882.
Chan, H.M. and Egeland, G.M. 2004. Fish consumption, mercury exposure, and heart
diseases. Nutr. Rev. 62, 68–72.
Stern AH. 2005. A review of the studies of the cardiovascular health effects of
methylmercury with consideration of their suitability for risk assessment. Environ. Res.
Salonen, J.T., Seppanen, K., Lakka, T.A., Salonen, R. and Kaplan, G.A. 2000.
Mercury accumulation and accelerated progression of carotid atherosclerosis: a
population-based prospective 4-year follow-up study in men in eastern Finland.
Atherosclerosis 148, 265–273.
Rissanen, T., Voutilainen, S., Nyyssonen, K., Lakka, T.A. and Salonen, J.T. 2000. Fish
oil-derived fatty acids, docosahexaenoic acid and docosapentaenoic acid, and the risk
of acute coronary events: the Kuopio ischaemic heart disease risk factor study.
Circulation 102, 2677–2679.
Virtanen, J.K., Voutilainen, S., Rissanen, T.H., Mursu, J., Tuomainen, T.P.,
Korhonen, M.J., Valkonen, V.P., Seppanen, K. et al. 2005. Mercury fish oils, and
risk of acute coronary events and cardiovascular disease, coronary heart disease, and
all-cause mortality in men in eastern Finland. Arterioscler. Thromb. Vasc. Biol. 25,
Yoshizawa, K., Rimm, E.B., Morris, J.S., Spate, V.L., Hsieh, C.C., Spiegelman, D.,
Stampfer, M.J. and Willett, W.C. 2002. Mercury and the risk of coronary heart disease
in men. N. Engl. J. Med. 347, 1755–1760.
Sorensen, N., Murata, K., Budtz-Jorgensen, E., Weihe, P. and Grandjean, P. 1999.
Prenatal methylmercury exposure as a cardiovascular risk factor at seven years of age.
Epidemiology. 10, 370–375.
Grandjean, P., Murata, K., Budtz-Jorgensen, E. and Weihe, P. 2004. Cardiac
autonomic activity in methylmercury neurotoxicity: 14-year follow-up of a Faroese
birth cohort. J. Pediatr. 144, 169–176.
Fillion, M., Mergler, D., Sousa Passos, C.J., Larribe, F., Lemire, M. and Guimaraes,
J.-R. A preliminary study of mercury exposure and blood pressure in the Brazilian
Amazon. Environ. Health 5, 29.
Vupputuri, S., Longnecker, M.P., Daniels, J.L., Guo, X. and Sandler, D.P. 2005. Blood
mercury level and blood pressure among US women: results from the National Health
and Nutrition Examination Survey 1999–2000. Environ. Res. 97, 195–200.
Itai, Y., Fujino, T., Ueno, K. and Motomatsu, Y. 2004. An epidemiological study of
the incidence of abnormal pregnancy in areas heavily contaminated with methylmer-
cury. Environ. Sci. 11, 83–97.
Silbergeld, E.K., Silva, I.A. and Nyland, J.F. 2005. Mercury and autoimmunity:
implications for occupational and environmental health. Toxicol. Appl. Pharmacol.
Hultman, P. and Hansson-Georgiadis, H. 1999. Methyl mercury-induced autoimmu-
nity in mice. Toxicol. Appl. Pharmacol. 154, 203–211.
Haggqvist, B., Havarinasab, S., Bjorn, E. and Hultman, P. 2005. The immunosup-
pressive effect of methylmercury does not preclude development of autoimmunity in
genetically susceptible mice. Toxicology 208, 149–164.
Grandjean, P., Weihe, P., Burse, V.W., Needham, L.L., Storr-Hansen, E., Heinzow, B.,
Debes, F., Murata, K. et al. 2001. Neurobehavioral deficits associated with PCB in 7-
year-old children prenatally exposed to seafood neurotoxicants. Neurotoxicol. Teratol.
Budtz-Jorgensen, E., Keiding, N., Grandjean, P. and White, R.F. 1999. Methylmercury
neurotoxicity independent of PCB exposure. Environ. Health Perspect. 107, 236–237.
Stewart, P.W., Reihman, J., Lonky, E.I., Darvill, T.J. and Pagano, J. 2003. Cognitive
development in preschool children prenatally exposed to PCBs and MeHg. Neuro-
toxicol. Teratol. 25, 11–22.
Ambio Vol. 36, No. 1, February 2007
? Royal Swedish Academy of Sciences 2007
135. Fang, J., Wang, K.X., Tang, J.L., Wang, Y.M., Ren, S.J., Wu, H.Y. and Wang, J. Download full-text
2004. Copper, lead, zinc, cadmium, mercury, and arsenic in marine products of
commerce from Zhejiang coastal area, China, May 1998. Bull. Environ. Contam.
Toxicol. 73, 583–590.
Takahashi, Y., Tsuruta, S., Hasegawa, J., Kameyama, Y. and Yoshida, M. 2001
Release of mercury from dental amalgam fillings in pregnant rats and distribution of
mercury in maternal and fetal tissues. Toxicology. 163, 115–126.
Takahashi, Y., Tsuruta, S., Arimoto, M., Tanaka, H. and Yoshida, M. 2003. Placental
transfer of mercury in pregnant rats which received dental amalgam restorations.
Toxicology 185, 23–33.
Pamphlett, R. and Kum-Jew, S. 2001. Mercury vapor uptake into the nervous system
of developing mice. Neurotoxicol. Teratol. 23, 191–196.
Fredriksson, A., Dencker, L., Archer, T. and Danielsson, B.R. 1996. Prenatal
coexposure to metallic mercury vapour and methylmercury produce interactive
behavioural changes in adult rats. Neurotoxicol. Teratol. 18, 129–134.
Burger, J., Stern, A.H. and Gochfeld, M. 2005. Mercury in commercial fish: optimizing
individual choices to reduce risk. Environ. Health. Perspect. 113, 266–271.
Dorea, J.G. and Barbosa, A.C. 2005. Fish consumption and blood mercury: proven
health benefits or probable neurotoxic risk? Regul. Toxicol. Pharmacol. 42, 249–
Wheatley, B. and Wheatley, M.A. 2000. Methylmercury and the health of indigenous
peoples: a risk management challenge for physical and social sciences and for public
health policy. Sci. Total. Environ. 259, 23–29.
Mahaffey, K.R. 2004. Fish and shellfish as dietary sources of methylmercury and the
omega-3 fatty acids, eicosahexaenoic acid and docosahexaenoic acid: risks and benefits.
Environ. Res. 95, 414–428.
Lucas, A., Stafford, M., Morley, R., Abbott, R., Stephenson, T., MacFadyen, U.,
Elias-Jones, A. and Clements, H. 1999. Efficacy and safety of long-chain polyunsat-
urated fatty acid supplementation of infant-formula milk: a randomised trial. Lancet
Hooper, L., Thompson, R.L., Harrison, R.A., Summerbell, C.D., Ness, A.R., Moore,
H.J., Worthington, H.V., Durrington, P.N. et al. 2006. Risks and benefits of omega 3
fats for mortality cardiovascular disease, and cancer: systematic review. BMJ 332, 752–
Paletz, E.M., Craig-Schmidt, M.C. and Newland, M.C. 2006. Gestational exposure to
methylmercury and n-3 fatty acids: effects on high- and low-rate operant behavior in
adulthood. Neurotoxicol. Teratol. 28, 59–73.
Beyrouty, P. and Chan, H.M. 2006. Co-consumption of selenium and vitamin E altered
the reproductive and developmental toxicity of methylmercury in rats. Neurotoxicol
Teratol. 28, 49–58.
Andersen, H.R. and Andersen, O. 1993. Effects of dietary alpha-tocopherol and beta-
carotene on lipid peroxidation induced by methyl mercuric chloride in mice. Pharmacol.
Toxicol. 73, 192–201.
National Research Council/National Academy of Sciences.
Institutional Means for Assessment of Risks in Public Health. Commission on Life
Sciences. 1983. Risk Assessment in the Federal Government: Managing the Process.
National Academy Press. Washington, DC.
FAO/WHO. 2003. Summary and Conclusions of the Sixty-First Meeting of the Joint
FAO/WHO Expert Committee on Food Additives (JECFA). Rome, Italy, 10–19 June
FAO/WHO. 2006. Summary and Conclusions of the Sixty-First Meeting of the Joint
FAO/WHO Expert Committee on Food Additives (JECFA). Rome, Italy, 20–29 June
World Health Organization. International Programme on Chemical Safety. Principles
for the Assessment of Risks to Human Health from Exposure to Chemicals.
Environmental Health Criteria 210., WHO, Geneva, Switzerland. (http://www.
inchem.org/documents/ehc/ehc/ehc210.htm accessed on 7/10/2006; see specifically
Figure 1. 00-Fold Uncertainty Factor).
Mahaffey, K.R. 2005. Mercury exposure: medical and public health issues. Trans. Am.
Clin. Climatol. Assoc. 116, 127–153.
Rice, D.C., Schoeny, R. and Mahaffey, K. 2003. Methods and rationale for derivation
of a reference dose for methylmercury by the U.S. EPA. Risk Anal. 23, 107–115.
Rice, D.C. 2004. The US EPA reference dose for methylmercury: sources of
uncertainty. Environ. Res. 95, 406–413.
149.Committee on the
Dr. Donna Mergler is a professor emerita in the Department of
Biological Sciences and the Institute for Environmental Sciences
at the University of Que ´bec at Montreal and a member of the
Centre for Interdisciplinary Research on Biology, Health,
Society, and the Environment (CINBIOSE), a WHO-PAHO
Collaborating Centre for the Prevention of Occupational and
Environmental Illness. She has carried out numerous studies
with populations exposed to mercury in Canada and Brazil, by
using an ecosystem approach that examines contaminants’
sources, pathways and effects, with a view to prevention
intervention. Her address: CINBIOSE, University of Quebec at
Montreal, CINBIOSE, CP 8888 succ Centreville, Montreal,
Quebec, Canada H3C 3P8.
Dr. Henry Anderson is a physician certified by the American
Board of Preventive Medicine with a subspecialty in occupational
and environmental medicine. He is a fellow of the American
College of Epidemiology and Chief Medical Officer and State
Environmental and Occupational Disease Epidemiologist with
the Wisconsin Department of Health and Family Services. He
has adjunct professor appointments in population health in the
Wisconsin School of Medicine and Public Health and the
Gaylord Nelson Institute for Environmental Studies. He has
conducted multiple research projects investigating human health
hazards of consumption of sport fish and developed the
effectiveness of public health advisories. His address: Wisconsin
Department of Health and Family Services, Division of Public
Health, 1 West Wilson St, Room 150, Madison, WI 53702, USA.
Dr. Laurie Hing Man Chan is a holder of the Dr. Donald Rix BC
Leadership Chair in Aboriginal Environmental Health at the
University of Northern British Columbia. His work involves both
basic and applied research on neurotoxic effects of mercury on
wildlife and human populations. He has conducted extensive
studies on the risk and benefits of the consumption of traditional
food among Indigenous Peoples. His address: University of
Northern British Columbia, 3333 University Way, Prince George,
BC Canada V2N 4Z9.
Dr. Kathryn Mahaffey is a toxicologist, who specialized in
research on nutrient-toxicant interactions and risk assessment
for toxic elements, including methylmercury. She has published
the distributional data on blood and hair mercury concentrations
indicating mercury exposures for the US population as part of
the National Health and Nutrition Examination Survey. Dr.
Mahaffey and two other scientists from the US Environmental
Protection Agency established the reference dose for methyl-
mercury, which is the most health protective risk assessment
available to date. Her address: 5025 Hawthorne Place NW,
Washington, DC 20016, USA.
Dr. Michael Murray is an environmental chemist and has been
Staff Scientist in the Great Lakes office of the National Wildlife
Federation since 1997. His scientific and science policy research
has been in diverse areas, ranging from contaminant sources,
environmental cycling, and environmental toxicology to human
health aspects of methylmercury, including exposure, effects,
and fish advisory protocols and communication. His address:
Great Lakes Natural Resource Center, National Wildlife Feder-
ation, 213 West Liberty St, Suite 200, Ann Arbor, MI 48104-
Dr. Mineshi Sakamoto, Director of the Department of Epidemi-
ology, National Institute for Minamata Disease, Minamata City,
Kumamoto Prefecture, Japan. He is a toxicologist and conducts
both epidemiological and experimental studies focused on the
heath effects of methylmercury, especially in the early stage of
development, when the brain is most vulnerable. His address:
National Institute for Minamata Disease, 058–18 Hama, Mina-
mata City, Kumamoto 867-0008, Japan.
Dr. Alan Stern is the Section Chief for Risk Assessment and
Toxicology in the Division of Science and Research of the New
Jersey Department of Environmental Protection and adjunct
associate professor in the School of Public Health, and the
Department of Environmental and Occupational Medicine of the
University of Medicine and Dentistry of New Jersey. He served
as a member of the National Research Council/National
Academy of Sciences Committee on the Toxicological Effects
of Methylmercury. His address: Division of Science, Research,
and Technology, New Jersey Department of Environmental
Protection, 401 East State St, Trenton, NJ 08625-0409, USA,
and University of Medicine and Dentistry of New Jersey-School
of Public Health, Piscataway, NJ, USA.
Ambio Vol. 36, No. 1, February 2007
? Royal Swedish Academy of Sciences 2007