United States
Environmental Protection
Agency
Environmental Criteria and
Assessment Office
Research Triangle Park NC 27711
Research arid Development
EPA/600/S8-84/019F Mar. 1987
<>EPA Project Summary
Mercury Health Effects Update:
Health Issue Assessment
This document summarizes the
health basis for the national emission
standard for mercury, originally set in
1973 and currently under review.
Mercury is unique among metals as the
only metal in liquid form at room
temperature. It exists in three oxidative
states—metallic (Hg°), mercurous
(Hgz++), and mercuric (Hg++) mercury—
and a wide variety of chemical forms,
the most important of which are com-
pounds of methyl mercury, mercuric
mercury, and the vapor of metallic
mercury. The global cycle of mercury
involves the emission of Hg° from land
and water surfaces to the atmosphere,
transport of Hg° in the atmosphere on
a widespread basis, possible conver-
sion to unidentified soluble species and
return to land and water through
various depositional processes. The
major source of human exposure to
methyl mercury is by diet through the
consumption of fish and fish products.
Mercury vapor is inhaled, whereas
uptake of inorganic and methyl mer-
cury compounds is primarily through
oral ingestion. Once absorbed, mercury
in all forms is distributed by the
bloodstream to all body tissues; how-
ever, tissue distribution of methyl
mercury is more uniform. Mercury
vapor and methyl mercury readily cross
the blood-brain and placenta! barriers.
Chronic exposure to mercury com-
pounds primarily affects the central
nervous system and kidneys. Depend-
ing upon the form of mercury and level
of intake, effects on the adult nervous
system can range from reversible
paresthesias and malaise to irreversible
destruction of neurons in the cerebellar
and visual cortices, leading to perma-
nent signs of ataxia and constriction of
the visual field. The fetus is most
sensitive to methyl mercury poisoning,
with effects in infants ranging from
psychomotor retardation to a severe
form of cerebral palsy. All prenatal
effects have to date been found
irreversible.
This Project Summary was devel-
oped by EPA's Environmental Criteria
and Assessment Office. Research
Triangle Park, NC. in EPA's Office of
Health and Environmental Assessment.
It announces key findings of the
research project that is fully docu-
mented in a separate report of the same
title (see Project Report ordering
information at back).
Summary and Conclusions
The National Emission
Standard of 1973
On April 6,1973, the U.S. Environmen-
tal Protection Agency promulgated a
National Emission Standard for Mercury
as 3 Hazardous Air Pollutant under
Section 112 of the Clean Air Act (38 FR
8820). The scientific information which
served as the health basis for the
standard is presented below.
By 1973, the fact that exposure to
metallic mercury vapor caused central
nervous system injury and renal damage
was well established. Prolonged expo-
sure to about 100 //g Hg/m3 of mercury
vapor involved a definite risk of mercury
intoxication. To determine the ambient
air level of mercury that did not impair
health, the impact of airborne burden
was considered in conjunction with
water and food burdens. Methyl mercury
compounds were considered the most
hazardous form of mercury and the
overall human body burden was believed
to be mainly derived from ingesting
methyl mercury in the diet, particularly
by fish which concentrate this form of
mercury through the food chain. When
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can methylate inorganic mercury, but thlj
most efficient and effective are certain
aerobes and facultative anaerobes. Strict
anaerobes such as methanogenic bac-
teria are less efficient. Both mono- and
dimethyl mercury compounds are
formed, depending on pH and other
conditions. Monomethyl mercury com-
pounds rapidly diffuse from the microor-
ganisms and rapidly accumulate in
aquatic food chains. The highest concen-
trations are found in large predatory fish
at the top of the aquatic food chain, e.g.,
trout, pike, and bass in fresh water and
tuna, swordfish, and red snapper in
oceanic water.
Many factors influence the methyl
mercury accumulation in fish. These
include not only the species of fish but
also the age of the fish, the levels of
mercury in sediment, the presence of
zooplankton, organic content of sedi-
ments and particulates in the water
column, water temperature, redox poten-
tial, and dissolved oxygen content.
Current studies suggest that long-
distance atmospheric transport and
acidification of rain water are correlated
with elevated levels of methyl mercury
in fresh water fish.
Methyl mercury compounds
demethylated by microorganisms in
environment. The accumulation o
methyl mercury in the food chain ulti-
mately depends upon an ecological
balance between methylation and
demethylation reactions as well as
trapping within organisms and chemical
complexes.
Levels of Mercury in Air,
Water and Food
Concentrations of mercury in the
atmosphere were estimated to be about
20 ng Hg/m3. However, more recent
unconfirmed observations indicate that
a more accurate estimate of average
atmospheric levels is in the range of 2-
10 ng Hg/m3. Concentrations of mercury
in fresh water are around 25 ng Hg/l,
most of which is probably in the mercuric
(Hg++) form. Concentrations of mercury
in fish and fish products (the dominant
food source of mercury in the human diet)
average from 100 to 220 ng Hg/g fish,
almost all (70 to 90 percent) of which
is methyl mercury. About two-thirds of
all fish consumers in the U.S. are tuna
eaters. However, on an individual con-
sumer basis, freshwater fish, e.g., pike,
bass, and trout, have the highest co
sumption rate. The diet greatly excee
the first standard was set, it was con-
sidered prudent to assume that expo-
sures to methyl mercury (diet) and
mercury vapor (air) were equivalent and
additive.
Also known by 1973 was the fact that
methyl mercury compounds, when
ingested in sufficient amounts, could
produce severe and irreversible damage
to the central nervous system both in the
adult and in the human fetus. Non-
specific symptoms such as paresthesia
occurred at the lowest body burden.
These first symptoms of intoxication
were observed in adults after prolonged
intake of about 300 fjg Hg as methyl
mercury per 70 kg body weight. It was
assumed that a safety factor of 10 would
provide satisfactory protection against
genetic lesions and poisoning of the fetus
and of children. Thus, it was determined
that the total intake of methyl mercury
should not exceed 30 fjg Hg/day/70 kg
body weight. Because the burdens of
mercury vapor and methyl mercury were
assumed to be equivalent and additive,
it followed that daily absorption of both
forms of mercury should not exceed 30
fjg Hg/70 kg body weight.
From estimates of average diets, over
a lengthy period, it was also determined
that mercury intakes of 10 jug Hg/day/
70 kg body weight might be expected.
Thus, to restrict total intake to 30 fjg Hg/
day/70 kg body weight, the average
mercury intake from air would have to
be limited to 20 jug Hg/70 kg body weight.
To maintain this level, the air would have
to contain an average concentration of
no more than 1 fjg Hg/m3, assuming the
70-kg adult inhaled 20 mVday.
Before promulgation of the standard,
data on the environmental transport of
mercury did not permit a clear assess-
ment of the impact of atmospheric
mercury emissions on aquatic and
terrestrial environments. Consequently,
the standard promulgated in 1973 was
intended to protect public health from the
effects of inhaled mercury, taking into
consideration dietary contributions to
total body burden. It did not, however,
account for the effects of atmospheric
mercury on other environments that
contribute to indirect exposures to
mercury.
Findings of Current Report
The findings of this report are based
mainly on a review of the scientific
literature published since the promulga-
tion of the standard in 1973. However,
literature published before 1973 and
relevant to assessing human health risks
from airborne mercury has also been
evaluated. The following is a summary
of the full document.
Mercury Background
Information
The Global Cycle
Despite intensive research in recent
years, many details, both quantitative
and qualitative on the global cycling of
mercury remain obscure. Elemental
mercury vapor, Hg°, emitted from land
and water surfaces, is the principal
species in the atmosphere and is respon-
sible for long-distance (100 to 1,000
kilometers) transport of mercury. The
residence time for this form of mercury
is months, possibly years. A "soluble"
form of mercury, of unknown chemical
species, is also present in the atmos-
phere but to a lesser extent. Soluble
mercury is returned by precipitation to
the earth's surface. Its residence time in
the atmosphere is believed to be days.
Widely varying estimates from 10 to
80 percent have been made for the
anthropogenic contribution of mercury to
the atmosphere. The figure for this report
is about 25 percent. Anthropogenic input
of mercury into bodies of fresh water is
believed to have increased mercury
levels in waters and sediments by factors
two to four as compared to eras before
the advent of man. Oceanic sediments
are the ultimate depository of mercury
in the form of insoluble mercuric sulfide.
The amount of mercury in oceanic water
is believed to be so large (tens of millions
of tons) that man's impact has been
negligible. However, anthropogenic
sources have had substantial impact on
the levels of mercury in aquatic orga-
nisms in marine coastal waters near
urban centers.
Biomethylation of Inorganic
Mercury
Within the context of the global cycle,
microbially-mediated methylation and
demethylation reactions of mercury take
place in sediments. These processes also
can take place within, and on, organic
paniculate microenvironments within
the water column, especially in eutrophic
and hypereutrophic aquatic systems.
These reactions play a key role in the
entry of methyl mercury into the human
diet. Microorganisms are capable of
methylating inorganic mercury by a non-
enzymic reaction with methyl cobala-
mines. Many types of microorganisms
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her media as a source of human
xposure and absorption of total
mercury.
Pharmacokinetics and
Biotransformation of
Mercury in Man and Animals—
Vapor of Metallic Mercury
Since 1973, new information has
become available on the pharmacokinet-
ics of inhaled vapor in man and on the
biotransformation of elemental mercury
in animal tissues. Although a complete
pharmacokinetic model has not yet been
established, some principal features
have been identified.
Mercury vapor is inhaled and adsorbed
through the skin. The extent of uptake
through the latter route is still unknown.
About 80 percent of the inhaled vapor
is retained and rapidly transferred to the
bloodstream where it is distributed to all
tissues in the body. Mercury readily
crosses the blood-brain and placenta!
barriers but accumulates to the greatest
extent in the kidney. It is mainly excreted
in urine and feces; however, it is also
excreted in sweat, saliva, and, to a small
extent, expired air. Because of the rapid
oxidation of absorbed mercury vapor to
Ijvalent mercury in mammalian tissues,
_ is likely that most of the mercury
accumulated in the kidney and other
tissues and excreted is in the divalent
form.
The whole body half-time of mercury
in man is approximately 50 to 70 days.
A rapid component in blood has a half-
time of about three days, and a slower
component has a half-time of about 30
days. A rapid component in the brain has
a half-time of about 21 days. There is
evidence of a much slower component
in the brain with a half-time of several
years.
Dissolved elemental mercury, Hg°, is
believed to be the most important mobile
species in mammalian tissues. It is
oxidized to Hg++ by the hydrogen-
peroxide-catalase complex in red blood
cells, liver, kidney and, probably, many
other tissues. Ethanol, at low, non-
intoxicating doses, can inhibit this
oxidation process and thereby lead to a
decreased retention of inhaled mercury.
Inorganic divalent mercury, Hg*+, is
reduced to Hg° in fiver and kidney tissues
and, probably, in other tissues as well.
The biochemical mechanism for this
reduction has not been identified in
mammalian cells but is well established
^t bacteria to the extent that even the
I^Bhetics, sequence of the enzymes, and
active site have been determined through
DNA-sequence analysis.
Inhaled mercury vapor can induce the
metal-binding protein metallothioein in
kidney tissue, and mercury-selenium
complexes may be formed after chronic
exposure.
Compounds of Inorganic
Mercury
Since 1973, new information has been
published on the kinetics of tracer doses
of inorganic mercury in man. However,
a complete pharmacokinetic model for
either mercurous or mercuric forms of
mercury has not yet been established.
Although mercurous chloride is slowly
and incompletely absorbed after oral
dosing, amounts sufficient to lead to
symptoms of mercurialism can be
absorbed chronically. Once absorbed,
mercurous mercury is probably con-
verted to the mercuric form. Ingested as
such, mercuric mercury has a less than
15 percent rate of absorption following
oral dosing. However, inferences from
animal studies suggest that absorption
of mercuric mercury may be as high as
50 percent in children and infants.
Mercuric mercury is distributed by the
bloodstream to all tissues in the body but
penetrates the blood-brain and placenta!
barriers to a much lesser extent (about
10 times less) than mercury vapor. As
with mercury vapor, the kidney concen-
trates inorganic mercury to a much
greater extent than other tissues and
excretes it mainly through urine and
feces.
The average biological half-time of a
tracer dose of divalent inorganic mercury
compounds in man is 42 days for the
whole body and 26 days for blood.
Methyl Mercury Compounds
New information on the kinetics of
methyl mercury in man and on the
mechanisms of biotransformation and
excretion does not change the picture
that existed when the 1973 standard was
promulgated. The pharmacokinetic
model of methyl mercury in man is much
further advanced than models for other
forms of mercury.
Oral doses of methyl mercury are 95
percent absorbed and are distributed
through the blood to all tissues of the
body within a few days. Like other forms
of mercury, methyl mercury readily
crosses the blood-brain and placenta!
barriers; however, unlike other forms,
tissue concentrations of methyl mercury
are much more uniform, with the kidney
having somewhat higher concentrations
than other tissues. The red blood cell-
to-plasma concentration ratio is typically
20:1, the blood-to-brain ratio is approx-
imately 1:5, and the blood-to-hair (newly
formed) ratio is 1:250.
About 80 percent of total methyl
mercury is excreted through feces.
Methyl mercury is also secreted in bile
and reabsorbed back into the blood-
stream to form an enterohepatic cycle.
The remainder is demethylated by flora
in the intestine and is excreted as
inorganic mercury. According to exper-
imental studies, a functioning enterohe-
patic cycle and active gut flora are
essential in order for mercury to be
excreted after doses of methyl mercury.
Suckling animals cannot excrete methyl
mercury in bile and, therefore, are unable
to excrete significant amounts of methyl
mercury from the body. How these
animal data compare to human data is
unknown since there is no available
information on human infants.
The average biological half-time of
methyl mercury in human adults is about
70 days in the whole body and 50 days
in the blood. The biological half-time in
the brain is probably similar to that of
the whole body or slightly longer. For
adults heavily exposed to methyl mer-
cury, wide range of biological half-times
(up to 120 days in the whole body) have
been reported. The reason for this is
unknown, but in experimental studies,
diet was shown to affect half-times in
the animals.
Toxic Effects of Mercury in
Man and Animals
The following section summarizes the
toxic effects of mercury in man and
animals, with emphasis on effects from
long-term low-level exposures. Where
possible, greater attention was focused
on direct observations of humans.
Vapor of Metallic Mercury
Since 1973, several clinical and epide-
miological studies have been published
on workers occupationally exposed to
mercury vapor. Generally, these studies
support findings that existed when the
mercury standard was promulgated.
Occupational studies showed that
chronic exposure to mercury vapor
affects primarily the central nervous
system and the kidneys. Effects asso-
ciated with the lowest exposure levels—
below 100 fig Hg/m3—produce non-
specific symptoms such as introversion,
insomnia, and anxiety. Biochemical
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alterations were observed in enzymes of
plasma and red blood cells, and increases
in urinary excretion of specific proteins
and enzymes occurred. Higher chronic
exposures produce more pronounced
effects in cognitive function, such as
short-term memory loss and changes in
personality traits (e.g., increased anxiety
and introversion). An overall body tremor,
typical to mercurialism cases, signals the
motor disfunctioning of the central
nervous system. No threshold for these
and other effects has been established,
although effects have not been seen at
air concentrations around 10/ug Hg/m3.
Renal effects may be mediated through
an autoimmune mechanism and may
exhibit wide individual ranges of sensi-
tivity. Experimental studies on this
sensitivity indicate the possiblity of a
genetic component related to the major
histocompatibility complex.
Effects on both the nervous system and
the kidneys are usually reversible,
particularly if the effects are mild.
Studies showed that motor effects
reverse more readily than cognitive and
neurotic effects.
Information is lacking on reproductive
and developmental effects of inhaled
mercury vapor.
Inorganic Compounds of
Mercury
There has been no new information on
the effects of inorganic compounds of
mercury on humans since 1973. Two
adult case studies showed that many
years of chronic oral intake of mercurous
chloride (250 mg/day) resulted in signs
of mercurialism and chronic renal failure.
Chronic oral exposure to mercurous
chloride has also caused acrodynia or
Pink's disease in children. Differences in
individual sensitivity were reported for
such effects, although, generally, acro-
dynia associated with urinary levels of
50 /ug Hg/l is reversible in children.
Comparison studies of mercury vapor
and mercurous sales indicate that
chronic exposure to compounds of
mercuric mercury would mainly affect
kidney function. However, there are no
experimental studies to support this.
Compounds of Methyl Mercury
Information, since 1973, is now avail-
able on a population exposed to dietary
methyl mercury. Findings from the study
population support evidence that existed
in 1973 and confirm the sensitivity of the
fetus to methyl mercury exposure. Milder
effects at dose levels lower than those
observed in 1973 have been reported for
the first time for exposed fetuses. The
possibility of delayed effects appearing
in adulthood has been raised.
Methyl mercury primarily damages the
central nervous system of adults and
fetuses. Prenatal exposures at the lowest
recorded levels produce signs of psy-
chomotor retardation in infants. Recent
studies show that male infants are more
sensitive than females at these low levels
of maternal dietary intake. Substantially
higher prenatal exposures, some only
occurring in the last trimester of preg-
nancy, produce a severe form of cerebral
palsy. Although detailed consequences
of methyl mercury poisoning are
unknown, prenatal effects appear to be
due to a derangement of the normal
processes of growth and development of
the central nervous system. Ongoing
studies, based on estimated blood levels
in the mother during pregnancy, show
that the fetus is about three times more
sensitive than the adult to methyl
mercury exposures.
Effects on the adult central nervous
system result in focal damage to specific
areas of the brain, principally the cortex
of the cerebellum and the visual cortex.
The first symptoms of methyl mercury
poisoning in adults are non-specific, e.g.,
paresthesias and malaise. These effects
are believed to have a low frequency
occurrence of about 5 percent in the
general population and are seen at blood
levels ranging from 200 to 500 ng Hg/
ml, which correspond to chronic oral
daily intakes of approximately 3 to 7 fjg
Hg/kg body weight. There is conflicting
evidence on the degree of reversibility
of these first symptoms of poisoning.
Dietary intake levels of methyl mercury
that produce irreversible destruction of
neurons in the cerebellar and visual
cortices leading to permanent signs of
ataxia and constriction of the visual field
are probably twice as high as those levels
causing mild symptoms.
Human Health Risk
Assessment of Mercury in Air
Direct Exposure Effects
Because the 1973 standard was based
on the direct exposure effects from
airborne mercury, taking into consider-
ation the contribution of dietary mercury
intake to total body burden, a similar
approach was taken here to determine
to what extent new information has
changed the perspective on direct risks
from mercury in air.
1
A new evaluation confirms that whil
mercury vapor still accounts for the major
fraction of airborne mercury, particulate
forms of mercury do exist in the atmos-
phere. The diet is by far the dominant,
if not the sole source of human exposure
to methyl mercury compounds. In addi-
tion, a current evaluation indicates that
the diet is also the dominant source of
compounds of inorganic mercury. In
comparing different routes of exposure,
contribution of airborne mercury is
between one-tenth and one-twentieth of
the total daily amount of mercury
absorbed into the body.
An analysis of dose-response and
dose-effect relationships shows that
current levels of mercury in the atmos-
phere, regardless of chemical species,
would present a negligible risk of adverse
health effects from direct airborne
exposures. Current atmospheric levels
are believed to be 20 ng Hg/m3 or less.
Effects of mercury vapor on human
health have not been detected below 1
fjg Hg/m3, and serious debilitating
effects have not been observed in
occupational settings where workers
have been exposed for months or years
to air concentrations below 100 /JQ Hg/
m3. Assuming that all the mercury in the
atmosphere was in the form of methy
mercury compounds, it would require
atmospheric concentration of 10 A
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^Tec
rcury in fish high enough to exceed
ederal guidelines, an important recent
finding is that high levels of methyl
mercury are also found in certain lakes
remote from anthropogenic sources.
Additionally, the problem of long-
distance transport is exacerbated by the
acidification of rainwater in certain areas
of the United States. A statistical corre-
lation was found between the acidity of
lakes and elevated levels of methyl
mercury in fish.
Many possible mechanisms for this
elevation may exist, but the overall effect
is that methyl mercury levels in fish are,
to some extent, indirectly affected by
airborne mercury and acid deposition.
The questions, therefore, arise as to what
extent changes in current atmospheric
levels would affect levels of methyl
mercury in edible freshwater fish, and
what would be the predicted impact on
human health?
The answer to the first question cannot
be definitively quantified at this time.
However, if airborne mercury levels
increased from current levels of 5 to 20
ng Hg/m3 to the 1,000 ng Hg/m3 level
that was used in setting emission limits
for source categories regulated by the
current standard, the environmental
insequences could be severe. This
larp rise in atmospheric air concentra-
tions would increase airborne mercury
in fish to unacceptably high levels.
To express quantitatively the health
impact this would have on the United
States would be difficult. Action guide-
lines by the Food and Drug Administra-
tion and state regulations already exist
that prohibit fish consumption if methyl
mercury levels exceed 1 (ig Hg/g wet
weight. The outcome, therefore, would
probably be the same as in Scandinavian
countries where elevated mercury con-
centrations in edible tissue of fish have
resulted in the banning of fish for
consumption from many freshwater
lakes. Local communities, such as reser-
vations of native American populations
whose main food source is freshwater
fish may suffer health consequences if
federal and local regulations do not
prevent the consumption of contami-
nated fish in these communities.
In conclusion, a more comprehensive
reevaluation of existing information is
required if the potential for indirect
exposure effects are to be considered.
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