United States
Environmental Protection
Agency
Office of Health and
Environmental Assessment
Washington DC 20460
Research and Development
EPA/600/S8-83/013F July 1987
&EPA Project Summary
Health Assessment
Document for Manganese
L. S. Erdreich and J. F. Stara
The Office of Health and Environ-
mental Assessment of the Office of
Research and Development, Environ-
mental Protection Agency (EPA), has
prepared a Health Assessment Docu-
ment (HAD) for manganese at the
request of the Office of Air Quality
Planning and Standards (OAQPS).
Manganese is one of several metals and
associated compounds emitted to the
ambient air that are currently being
studied by the EPA to determine
whether they should be regulated as
hazardous air pollutants under the
Clean Air Act. This HAD is designed
to be used by OAQPS for decision
making.
In the development of the current
assessment document, the scientific
literature has been inventoried, key
studies have been evaluated and sum-
maries and conclusions have been
directed at qualitatively identifying the
toxic effects of manganese. Observed
effect levels and dose-response rela-
tionships are discussed in order to
identify the critical effect and to place
adverse health responses in perspective
with observed environmental levels.
This Project Summary was devel-
oped by EPA's Office of Health and
Environmental Assessment. Environ-
mental Criteria and Assessment Office.
Cincinnati, OH, to announce key find-
ings of the research project that is fully
documented in a separate report of the
same title (see Project Report ordering
information at back).
Introduction
This assessment document is based on
original publications, although the over-
all knowledge covered by a number of
reviews and reports was also considered.
The references cited were selected to
reflect current knowledge on those
issues that are most relevant for a health
assessment of manganese in the
environment.
The rationale for structuring this
document is based primarily on two
major issues, exposure and response.
The first portion of the document is
devoted to manganese in the environ-
ment: physical and chemical properties,
the monitoring of manganese in various
media, natural and human-made
sources, the transport and distribution of
manganese within environmental media,
and the levels of exposure. The second
part is devoted to biological responses
in laboratory animals and humans,
including metabolism, pharmacokinet-
ics, mechanisms of toxicity, as well as
toxicological effects of manganese.
General Properties and
Background Information
Manganese is a ubiquitous element in
the earth's crust, in water and in par-
ticulate matter in the atmosphere. In the
ground state, manganese is a gray-white
metal resembling iron, but harder and
more brittle. Manganese metal forms
numerous alloys with iron, aluminum
and other metals.
There are numerous valence states for
manganese, with the divalent form giving
the most stable salts and the tetravalent
form giving the most stable oxide. The
chlorides, nitrates and sulfates of man-
ganese are highly soluble in water, but
the oxides, carbonates and hydroxides
are only sparingly soluble. The divalent
compounds are stable in acid solution but
are readily oxidized in alkaline condi-
tions. The heptavalent form is found only
in oxy-compounds.
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Sources of Manganese in the
Environment
Manganese is the twelfth most abund-
ant element and fifth most abundant
metal in the earth's crust. While man-
ganese does not exist free in nature, it
is a major constituent in at least 100
minerals and an accessory element in
>200 others. Its concentration in various
crustal components and soils ranges
from near zero to 7000 fjg/g, depending
on the nature of the rock or soil. Crustal
materials are an important source of
atmospheric manganese due to natural
and anthropogenic activities (e.g., agri-
culture, transportation, earth-moving),
which generate suspended dusts and
soils. The resulting aerosols consist
primarily of coarse particles (>2.5 fjm).
Manganese is also released to the
atmosphere by manufacturing pro-
cesses. Ferromanganese furnace emis-
sions are composed mainly of fine
paniculate «2.5 //m) with a high man-
ganese content (15-25%). Ferroalloy
manufacture was the largest manganese
emission source in 1968. Control tech-
nology has improved and production
volume has diminished, so, although
current estimates are not available,
levels are probably lower. Iron and steel
manufacture is also an important man-
ganese source. Manganese content of
emitted particles is lower (0.5-8.7%), but
overall production volume is greater than
for manganese-containing ferroalloys.
Fossil fuel combustion also results in
manganese release. The manganese
content of coal is 5-80 jug/g. Fly ash is
about equal to soil in manganese content
(150-1200 /ug/g) but contains particles
finer in size. This is an important
manganese source because of the
volume of coal burned each year. Com-
bustion of residual oil is less important
because of its lower manganese content.
About 15-30% of manganese derivatives
combusted in gasoline are emitted from
the tailpipe.
The relative importance of emission
sources influencing manganese concen-
tration at a given monitoring location can
be estimated by chemical mass balance
studies. Studies in St. Louis and Denver
suggest that crustal sources are more
important in the coarse than in the fine
aerosol fraction. Conversely, combustion
sources such as refuse incineration and
vehicle emissions predominantly affect
the fine fraction. In an area of steel
manufacturing, the influence of this
process is seen in both the fine and
coarse fractions.
Another means of determining the
influence of noncrustal sources is to
compare the ratio of manganese and
aluminum in an aerosol with that in soils.
The derived enrichment factor (EF)
indicates the magnitude of influences
from noncrustal sources. In most areas,
the EF for coarse aerosols in near unity,
indicating crustal origin, but the EF for
the fine fraction is substantially higher,
indicating a greater influence from
noncrustal sources of emission.
Environmental Fate and
Transport Processes
A general overview of man's impact
on the geochemical cycling of manga-
nese shows a nearly doubled flux from
the land to the atmosphere due to
industrial emissions, and a tripled flux
from land to oceans, by rivers, due to soil
loss from agriculture and deforestation.
Atmospheric manganese is present m
several forms. Coarse dusts contain
manganese as oxides, hydroxides, or
carbonates at low concentrations (< 1
mg Mn/g). Manganese from smelting or
combustion processes is often present in
fine particles with high concentrations
of manganese as oxides (up to 250 mg/
g). Organic manganese usually is not
present in detectable concentrations.
Oxides of manganese are thought to
undergo atmospheric reactions with
sulfur dioxide or nitrogen dioxide to give
the divalent sulfate or nitrate salts.
Manganous sulfate has been shown to
catalyze SOz transformation to sulfuric
acid, but the manganese concentration
necessary for a significant catalytic effect
has been disputed.
In water or soil, manganese is usually
present as the divalent or tetravalent
form. Divalent manganese (present as
the hexaquo ion) is soluble and relatively
stable in neutral or acidic conditions.
Chemical oxidation to the insoluble
tetravalent form takes place only at a pH
above 8 or 9, and chemical reduction of
the tetravalent form occurs only at pH
<5.5. At intermediate pH, interconver-
sion occurs only by microbial mediation.
Manganese tends to be mobile in
oxygen-poor soils and in the ground-
water environment. Upon entering sur-
face water, manganese is oxidized and
precipitated, primarily by bacterial action.
If the sediments are transported to a
reducing environment such as a lake
bottom, however, microbial reduction
can occur, causing re-release of divalent
manganese to the water column.
Environmental Levels and
Exposures '
Nationwide air sampling has been
conducted in some form since 1953.
Analytical methodology has improved
and monitoring stations have changed,
complicating any analysis of trends in
manganese concentration. However, it is
evident that manganese concentrations
m ambient air have declined during the
period of record. The arithmetic mean
manganese concentration of urban
samples was 0.11 /jg/m3 in 1953-1957,
0.073 fjg/m3 in 1966-1967, and
decreased to 0.033 fjg/m3 by 1982. In
1953-1957, the percentage of urban
stations with an annual average of >0.3
/ug/m3 was —10%. By 1969 these had
dropped to <4%, and since 1972 the
number has been <1%.
The highest manganese concentra-
tions, with some observations exceeding
10 /yg/m3, were seen in the 1960s in
areas of ferromanganese manufacture.
More recent measurements in these
areas indicated that decreases of at least
an order of magnitude had occurred,
although definitive studies were not
available.
In most cases where comparable data
on total suspended paniculate (TSP]
were available, decreases in TSP alsc
occurred but were usually smaller in
magnitude than those for manganese
This would suggest that the observec
reductions in manganese were more
than a simple reflection of TSP improve-
ments, indicating specific reductions ol
manganese emissions.
Biological Role
Although manganese has been showr
to be essential for many species o
animals, as yet there are no well-define<
occurrences of manganese deficiency ir
humans. Manganese deficiency ha:
been demonstrated in mice, rats, rabbit!
and guinea pigs. The main manifesta
tions of manganese deficiency are thosi
associated with skeletal abnormalities
impaired growth, ataxia of the newborn
and defects in lipid and carbohydrati
metabolism. Although the daily require
mem of manganese for development am
growth has not been adequately studiec
it was accepted that diets containing 5(
mg/kg manganese are adequate for mos
of the laboratory animals.
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Synergistic/Antagonistic
Factor
It is generally accepted that under
normal conditions 3-4% of orally
ingested manganese is absorbed in man
and other mammalian species. Gastroin-
testinal absorption of manganese and
iron may be competitive. This interaction
has a limited relevance to human risk
assessment under normal conditions.
However, it does lead to the hypothesis
that iron-deficient individuals may be
more sensitive to manganese than the
normal individual.
Evidence is accumulating that during
mammalian development manganese
absorption and retention are markedly
increased giving rise to increased tissue
accumulation of manganese.
Manganese does penetrate the blood-
brain barrier and the placental barrier.
Studies in animals indicate a higher
manganese concentration in suckling
animals, especially in the brain.
Acute Exposure
The average LD50 observed in different
animal experiments indicates that the
oral dose values range from 400-830 mg
Mn/kg of soluble manganese com-
pounds, much higher than the 38-64 mg
Mn/kg for parenteral injection. The
toxicity of manganese varies with the
chemical form in which it is administered
to animals. Acute poisoning by manga-
nese in humans is very rare. It may occur
following accidental or intentional inges-
tion of large amounts of manganese
compounds. Along with a number of
other metals, freshly formed manganese
oxide fumes have been reported to cause
metal fume fever.
Chronic Exposure
Chronic manganese poisoning, a neu-
rologic syndrome also known as manga-
nism, results from occupational expo-
sures to manganese dusts, sometimes
after only a few months of exposure.
Manganism begins with a psychiatric
disturbance followed by a neurologic
phase resembling Parkinson's disease,
and has been well described in the
literature with clinical details. It has been
reported in workers in ore crushing and
packing mills, in the production of
ferroalloys, in the use of manganese
alloys in the steel industry and in the
manufacture of dry cell batteries and
welding rods. Very high concentrations
of manganese have been found in mines
where cases of manganism were
reported. The manganese air concentra-
tion in the immediate vicinity of rock
drilling in Moroccan mines was —450
mg/m3 in one mine and ~250 mg/m3
in another. In two reports from Chilean
mines, the air concentrations of manga-
nese varied from 62.5-250 mg/m3 and
from 0.5-46 mg/m3, respectively. Earlier
studies in miners reported advanced
cases of manganism, but more recent
studies report neurological symptoms
and a few signs where the exposure was
at much lower concentrations. This may
reflect either a different chemical form
and particle size of the inhaled manga-
nese or a straight dose-response effect.
The inconsistencies in clinical examina-
tion make it difficult to compare across
studies.
The full clinical picture of chronic
manganese poisoning is reported less
frequently at exposure levels below 5
mg/m3. Studies reporting effects at the
above levels describe signs or symptoms
that cannot be definitely attributed to
manganese. Tremor at rest has been
reported as the major effect on workers
in an electrode plant exposed to 2-30//g/
m3 (0.002-0.03 mg/m3), although dura-
tion of exposure was not fully detailed.
The prevalence of a few signs in workers
exposed to 0.3-5 mg/m3 and 0.4-2.6 mg/
m3 suggest that the effects may occur
at exposures as low as 0.3 mg/m3 (300
/yg/m3). The data available for identifying
effect levels below this level is equivocal
or inadequate. There is no clear-cut
evidence of chronic manganese poison-
ing under 5 mg/m3. This is further
complicated by the fact that good biolog-
ical indicators of manganese exposure
are not presently available. Conse-
quently, studies directed toward clearly
defining the dose-effect relationship will
undoubtedly facilitate a more realistic
estimate of the risk to developing
manganism.
A high incidence of pneumonia and
other respiratory ailments has been
reported in workers with occupational
exposure to manganese and in inhabit-
ants living around factories manufactur-
ing ferromanganese or manganese
alloys. The increased incidence of pul-
monary disease found in exposure to low
concentrations of manganese is not
necessarily directly attributable to man-
ganese itself. Manganese exposure may
increase susceptibility to pneumonia or
other acute respiratory diseases by
disturbing the normal mechanism of lung
clearance.
Some reported animal studies imply a
carcinogenic potential for manganese,
but the data are inadequate to support
this conclusion. No epidemiologic infor-
mation relating manganese exposure to
cancer occurrence in humans has been
located. Using the International Agency
for Research in Cancer criteria, the
available evidence for manganese carci-
nogenicity would be rated inadequate for
animals and "no data available" for
humans.
The broad exposure ranges, the incom-
plete descriptions of chemical form and
particle size are insufficient to relate
response to exposure characteristics. In
order to obtain definitive dose response
data, a cohort study is needed, including
documented clinical examinations, more
accurate exposure characterization, and
exposure data on individuals. All
members of the cohort should be fol-
lowed for neurological signs for at least
20 years with clear reporting of any lost
data.
Existing Guidelines,
Recommendations and
Standards
In the United States, the American
Conference of Governmental and Indus-
trial Hygienists has recommended a 5
mg/m3 as both the time-weighted aver-
age threshold limit value (TWA-TLV) and
the short-term exposure limit for man-
ganese in air. This value is based on
observations of poisoning in humans at
concentrations near or above the recom-
mended TLV. The National Institute for
Occupational Safety and Health has not
recommended an occupational criterion
for exposure to airborne manganese, and
the Occupational Safety and Health
Administration has not promulgated a
standard for manganese exposure. Occu-
pational air standards in some other
countries, as summarized by the Inter-
national Labor Office, are as follows:
Country mg/Mn/m3 Comment
Belgium
Czechoslovakia
Japan
Poland
Roumania
Switzerland
USSR
5
2
6
5
0.3
1
3
5
03
Ceiling value
Ceiling value
Ceiling value
Celling value
The World Health Organization (WHO)
recommends a criterion of 0.3 mg/m3 for
respirable manganese in occupational
exposures.
No toxicity-based criteria for standards
for manganese in freshwater have been
proposed. The WHO, the U.S. Public
Health Service, and the U.S. EPA recom-
mended a concentration of 0.05 mg/l in
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water to prevent undesirable taste and
discoloration. In the USSR, the recom-
mended maximum permissible concen-
trations is 0.1 mg/l. The recom-
mendation is intended to prevent the
discoloration of water.
For marine waters, the U.S. EPA has
recommended a criterion for manganese
of 0.1 mg/l for the protection of consu-
mers of marine mollusks. Although the
rationale for this criterion is not detailed,
it is partially based on the observation
that manganese can bioaccumulate by
factors as high as 12,000 in marine
mollusks.
Summary and Conclusions
Manganese is an essential element for
humans and animals. The concentration
of manganese present in individual
tissues, particularly in the blood, is
controlled after ingestion by homeostatic
mechanisms and remains remarkably
constant despite rapid fluctuations in
intake. The main routes of absorption are
the gastrointestinal and respiratory
tracts. Acute poisoning by manganese
may occur in exceptional circumstances
where large amounts of manganese
compounds are ingested or inhaled.
Freshly formed manganese oxide fumes
of respirable particle size can cause
metal fume fever but are not believed to
cause permanent damage. The most
pronounced toxic effects of manganese
are a central nervous system syndrome
known as chronic manganese poisoning
(manganism) and manganese pneumo-
nitis.
While manganism and its association
with manganese has been well des-
cribed, a dose-response relationship in
man cannot be evaluated because dura-
tion of exposure is not well documented.
Also, early signs of the disease were
sought in only a few studies in humans
and none of the reported studies
employed a standard cohort design (e.g.,
there was no follow-up or comprehen-
sive characterization of the exposed
populations).
The EPA authors L. S. Erdreich andJ. F. Stara (deceased} (also the EPA Project
Officers, see below) are with the Environmental Criteria and Assessment
Office, Cincinnati. OH 45268.
The complete report entitled "Health Assessment Document for Manganese,"
(Order No. PB 84-229954; Cost: $30.95, subject to change)
will be available only from:
National Technical Information Service
5285 Port Royal Road
Springfield. VA22161
Telephone: 703-487-4650
L. S. Erdreich can be contacted at:
Environmental Criteria and Assessment Office
U.S. Environmental Protection Agency
Cincinnati, OH 45268
liUilili.ilililliiliiluliltl
United States
Center for Environmental Research
U.S.OFFICIALMA8.
Environmental Protection
Agency
Information
Cincinnati OH 45268
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