United States
Environmental Protection
Agency
Office of Health and
Environmental Assessment
Washington DC 20460
Research and Development
EPA/600/S8-83/012 July 1990
&EPA Project Summary
Health Assessment
Document for Nickel
The predominate atmospheric
forms of nickel are as sulfate, oxides,
and complex oxides. Nickel also
occurs in ambient and drinking water
and soils.
Routes of intake for man are
inhalation, ingestion, and
percutaneous absorption. Pulmonary
absorption varies according to
chemical and physical form of the
compound. While gastrointestinal
intake ranges from 300 to 500 pg
daily, absorption is only one to ten
percent of intake. Percutaneous
absorption, usually through contact
with nickel alloys in the household, is
related to hypersensitivity and skin
disorders. Inhaled nickel compounds
lead to highest levels in lung, brain,
kidney and liver.
Nickel exposure produces
chronic dermatological, respiratory,
endocrine and cardiovascular effects.
Reproductive and developmental
effects have been found in animals
but not humans. Various nickel
compounds have been tested for
mutagenicity, demonstrating the
ability of nickel compounds to
produce genotoxic effects; the
translation of these effects into
actual mutations is still not clearly
understood. There is evidence both
in humans and animals for the
carcinogenicity of nickel in some
forms. Lifetime cancer risks for
continuous inhalation exposure at 1
i>g nickel/m3 have been estimated for
nickel refinery dust and nickel
subsulfide-
There is a growing evidence that
nickel may be an essential element
for humans.
This Project Summary was
developed by EPA's Environmental
Criteria and Assessment Office, Re-
search Triangle Park, NC, to announce
key findings of the research project
that is fully documented in a separate
report of the same title (see Project
Report ordering information at back).
Background
Chemical/Physical Properties of
Nickel and Nickel Compounds
Nickel is found in nature as a
component of silicate, sulfide. or,
occasionally, arsenide ores. It is a
valuable mineral commodity because of
its resistance to corrosion and its
siderophilic nature which facilitates the
formation of nickel-iron alloys. Stainless
steel is the most well-known alloy; others
include permanent magnet and super
alloys, used in radios, generators and
turbochargers, and copper-nickel alloys,
used when resistance to extreme stress
and temperature is required. Other uses
for nickel and its compounds include
electroplating baths, batteries, textile
dyes and mordants, and catalysts.
As a member of the transition metal
series, nickel is uniquely resistant to
alkalis, but generally dissolves in dilute
oxidizing acids. Nickel may exist in many
oxidation states, the most prevalent being
Ni2*. Of some commercial and/or
environmental significance are several
binary nickel compounds including nickel
oxide (both black, which is chemically
reactive, and green, which is inert and
refractory) and complex oxides of nickel,
nickel sulfate, nickel nitrate, nickel
carbonate, nickel hydroxide, nickel
sulfide, and nickel carbonyl.
Nickel in Ambient Air
In the atmosphere, nickel is present as
a constituent of suspended particulate
matter. The primary stationary source
categories that emit nickel into ambient
air are: primary production sources
-------
(nickel ore mining/smelting and nickel
matte refining); combustion and
incineration sources (coal and oil burning
units in utility, industrial, commercial and
residential use sectors, and municipal
and sewage sludge incinerators); high
temperature metallurgical sources (steel
manufacturing, nickel alloy
manufacturing, secondary nickel
smelting, secondary nonferrous metals
smelting, and iron and steel foundries);
chemical and catalyst sources (nickel
chemical manufacturing, electroplating,
nickel-cadmium battery manufacturing
and catalyst production, use and
reclamation); and miscellaneous sources
(co-product nickel recovery, cement
manufacturing, coke ovens, asbestos
mining/milling and cooling towers).
While nickel in its elemental state can
be measured in the ambient air,
determination of specific compounds is
difficult to achieve. Techniques used to
break down inorganic compounds into
their ionic or atomic states change the
form of the compound in the attempt to
determine the total concentration of the
element. In addition, the very low level of
nickel present in ambient air samples
(average of 0.008 iig/m3; 1982 figures)
complicates the situation. Nevertheless,
by analyzing the physical and chemical
properties of nickel, the forms of nickel
input to various source processes, and
the reaction conditions encountered in
various source categories, it is possible
to estimate forms of nickel emitted into
the ambient air. From such analyses, the
predominant forms appear to be nickel
sulfate, complex oxides of nickel and
other metals (chiefly iron), nickel oxide,
and to a much lesser extent, metallic
nickel and nickel subsulfide. Of the total
volume of nickel emitted into the ambient
air, the greatest contribution is from the
combustion of fossil fuels in which nickel
appears to be in the form of nickel
sulfate, followed by lesser amounts of
nickel oxide and complex metal oxides
containing nickel.
Nickel in Ambient and Drinking
Water
Nickel is usually found as Ni2 + in
aquatic systems. Chemical factors which
can affect the form of nickel in aquatic
systems include pH and the presence of
organic and inorganic ligands. Nickel is
found in ambient waters as a result of
chemical and physical degradation of
rocks and soils, deposition of
atmospheric nickel-containing paniculate
matter, and direct (and indirect)
discharges from industrial processes. Of
the anthropogenic sources of nickel in
water, primary nickel production,
metallurgical processes, fossil fuel
combustion and incineration, and
chemical and catalyst production are
predominant.
Measurements of nickel in aqueous
environments are generally reported as
total nickel. The mean concentration of
nickel in U.S. surface waters (based upon
1982 figures) ranges from less than 5 vig/l
in the Great Basin of southern Nevada to
greater than 600 ng/l in the Ohio River
Basin. Concentrations in groundwater are
also highly variable with means ranging
from 4430 ng/l in the Ohio River basin to
2.95 jig/l in the Upper Mississippi River
basin (based upon 1982 figures). A mean
nickel concentration of 4.8 pg/l has been
calculated for drinking water from eight
metropolitan areas (based upon 1970
figures).
Specific forms of nickel in ambient
waters have not been reported; however,
inferences of species expected to be
found in effluents can be made based on
the nature of source processes and the
aqueous chemistry of nickel. Nickel
species in wastewaters from the major
anthropogenic sources are likely to
include dissolved salts (such as sulfates,
chlorides and phosphates), insoluble
oxides of nickel and other metals, and
metallic nickel powder.
Nickel in Soil and Sediment
Many of the same chemical and
physical properties which govern the
behavior of nickel in aqueous
environments also affect the behavior of
nickel in soils and sediments. In soils,
nickel may exist in several forms such as
inorganic crystalline minerals or
precipitates, as free ion or chelated metal
complexes in soil solution, and as
complexed with, or adsorbed to,
inorganic cation exchange surfaces such
as clays.
Naturally occurring nickel in soils
depends upon the elemental composition
of rocks in the upper crust of the earth.
The natural concentration of nickel in
soils usually ranges from 5 to 500 ppm,
with an average level estimated at 50
ppm. Soils derived from serpentine rock
(naturally high in nickel content) may
contain nickel levels up to 5000 ppm.
Anthropogenic sources of nickel to soils
include emissions from primary smelters
and metal refineries, disposal of sewage
sludge or application of sludge as a
fertilizer, auto emissions, and emissions
from electric power utilities; the most
significant of these sources being
smelting and refining operations and
sludge applications. Depending upon tl
source, nickel soil concentrations ha'
been reported to range from 0.90 pp
(from auto emissions) to as much
24,000 ppm (near metal refineries)
53,000 ppm (from dried sludge). The
figures are based upon elemental nicl
as specific forms of nickel in soils hs
not been reported.
Nickel in Plants and Food
The primary route for nicl
accumulation in plants is through n
uptake from soil. Nickel is present
vegetation usually below the 1 ppm le'
although plants grown in serpentine s<
have been shown to have me
concentrations as high as 100 ppm.
crops grown in soils where sew;
sludge has been applied, nic
concentrations have been reported
range from 0.3 to 1150 ppm.
. In addition to nickel uptake via s<
food processing methods have b
shown to add to nickel levels alre
present in foodstuffs via leaching f
nickel-containing alloys in fo
processing equipment, the milling
flour, and the catalytic hydrogenatio
fats and oils by use of nickel catah
The nickel content of various classe
food has been reported to range I
0.02 ppm (wet weight) in food items :
as fresh tomatoes, frozen swordfish
pork chops to 9.80 ppm in cocoa.
The Global Cycling of Nickel
Nickel in all environme
compartments is continuously transf<
between compartments by na
chemical and physical processes su
weathering, erosion, runoff, precipit;
stream/river flow and leaching. N
introduced into the environmen
anthropogenic means is subject tc
same chemical and physical proce
but can account for increased anr
concentrations in all environm
compartments. The ultimate sin
nickel is the ocean; however, the cy
continuous because some nicke
leave the ocean as sea spray aei
which burst and release minute r
containing particles into the atmospl
Nickel Metabolism
Absorption
Routes of nickel intake for ma
animals are inhalation, ingestioi
percutaneous absorption. Pare
exposure of experimental anim
mainly of importance in assessir
kinetics of nickel transport, distri
and excretion. Parenteral expos
-------
humans to nickel from medications,
emodialysis and protheses can be a
significant problem to certain sections of
the population.
The relative amount of inhaled nickel
which is absorbed from various
compartments of the pulmonary tract is a
function of both chemical and physical
forms. Insoluble particulate nickel
deposited in the various respiratory
compartments in both occupationally
exposed subjects and the general
population is very slowly absorbed with
accumulation over time. Experimental
animal data show very slow clearance of
deposited insoluble nickel oxide from the
respiratory tract, moderate clearance
(around 3 days) of the carbonate and
rapid clearance (hours to several days) of
soluble nickel salts. In the case of nickel
oxide, clearance from lung involves both
direct absorption into the blood stream
and clearance via the lymphatic system.
While most respiratory absorption studies
demonstrate that differences in
compound solubilities relate to pulmonary
;learance, with inert compounds having
'elatively slower clearance, the
'elationship of respiratory absorption to
pathogenic effects is still not clearly
jnderstood.
Gastrointestinal intake of nickel by
nan is relatively high compared to other
oxic elements and can be partially
iccounted for by contributions of nickel
:rom utensils and equipment in
processing and home preparation of food.
Average human dietary values range
rom 300 to 500 ng daily with absorption
>n the order of one to ten percent.
Decent studies show that nickel
)ioavailability in human diets appears to
)e dependent on dietary composition.
Percutaneous absorption of nickel
>ccurs and is related to nickel-induced
lypersensitivity and skin disorders;
lowever, the extent to which nickel
inters the bloodstream by way of the
kin cannot be stated at the present time.
'ransplacental transfer of nickel has been
videnced in rats and mice and several
eports indicate that such passage can
Iso occur in man.
ransport and Distribution
The kinetic processes governing the
ansport and distribution of nickel in
arious organisms are dependent upon
te modes of absorption, the rate and
vel of nickel exposure, the chemical
>rm of nickel and the physiological
tatus of the organism. Absorbed nickel
carried by the blood, and although the
xtent of partitioning between
rythrocytes and plasma or serum cannot
be precisely stated, serum levels can be
useful indicators of blood burden and, to
a more limited extent, exposure status
(excluding exposure to insoluble and
unabsorbed nickel deposited in lungs). In
unexposed individuals, serum nickel
values are approximately 0.2 to 0.3 jig/dl.
Albumin is the main macromolecular
carrier of nickel in a number of species,
including man, while in man and rabbit
there also appear to be nickel-specific
proteins
Tissue distribution of absorbed nickel
appears to be dependent on the route of
intake. Inhaled nickel carbonyl leads to
highest levels in lung, brain, kidney, liver,
and adrenals. Parenteral administration of
nickel salts usually results in highest
levels in the kidney, with significant
uptake shown by endocrine glands, liver,
and lung. Nickel absorption and tissue
distribution following oral exposure
appear to be dependent upon the relative
amounts of the agent employed. Animal
studies suggest that a homeostatic
mechanism exists to regulate low levels
of nickel intake (around 5 ppm), but that
such regulation is overwhelmed in the
face of large levels of nickel challenge
Based on animal studies, nickel
appears to have a very short half-time m
the body of several days with little
evidence for tissue accumulation. Human
studies have shown that age-dependent
accumulation of nickel appears to occur
only in the case of the lung with other
soft and mineralizing tissues showing no
accumulation. There are very few data
concerning nickel tissue levels and total
body burden in humans. One estimate is
that the total nickel burden in man is
about 10 mg.
Excretion
The excretory routes for nickel in man
and animals depend in part on the
chemical forms of nickel and the mode of
nickel intake. Unabsorbed dietary nickel
is lost in the feces. Urinary excretion in
man and animals is usually the major
clearance route for absorbed nickel, with
biliary excretion also occurring in
experimental animals. Sweat can also
constitute a major route of nickel
excretion. Recent studies suggest that
normal levels of nickel in urine vary from
2 to 4 ug/l
While hair deposition of nickel also
appears to be an excretory mechanism,
the relative magnitude of this route,
compared to urinary excretion, is not fully
known at present.
Factors Affecting Nickel
Metabolism
A number of disease states or other
physiological stresses can influence
nickel metabolism in man. In particular,
heart and renal disease, burn trauma, and
heat exposure can either raise or lower
serum nickel levels. To what extent
factors such as age or nutritional status
affect nickel metabolism in man is
presently unknown. In animals, both
antagonistic and synergistic relationships
have been demonstrated for both
nutritional factors and other toxicants.
Nickel Toxicology
Subcellular and Cellular Aspects
of Nickel Toxicity
Nickel, as the divalent ion, is known to
bind to a variety of biomolecular species,
such as nucleic acids and proteins, as
well as their constituent units. Strongest
interactions occur with sulfhydral. aza-
and amino groups with binding to peptide
(amido) and carboxylate ligands also
possible.
A number of reports in the literature
describe various in vivo and in vitro
effects of various nickel compounds on
enzyme systems as well as nucleic acid
and protein biosynthesis. In particular,
effects are seen on drug- detoxifying
enzymes in various tissues, enzymes that
mediate carbohydrate metabolism and
enzymes that mediate transmembrane
transport, such as ATPase.
A number of ultrastructural alterations
are seen in cellular organelles from
experimental animals exposed to various
nickel compounds Most of these
changes involve the nucleus and
mitochondria and range from slight
changes in conformation to evidence of
degeneration.
The behavior of cells in culture
exposed to nickel compounds has been
reported from different laboratories.
Nickel ion, at varying levels, affects both
viability and phagocytic activity of
alveolar macrophages, which may explain
the role of nickel in retarding resistance
to respiratory tract infections in animal
models.
Nickel-induced human lymphocyte
transformation has been studied as a
sensitive in vitro screening technique for
nickel hypersensitivity and this procedure
appears to be a reliable alternative to
classical patch testing.
Various studies have been directed to
the response of cells in culture to
-------
insoluble nickel dusts which are
implicated in human and experimental
animal carcinogenesis. In particular, rat
embryo myoblasts show drastic reduction
of mitotic index and viability when
exposed to nickel subsulfide.
Acute Effects of Nickel
Exposure
In terms of human health effects,
probably the most acutely toxic nickel
compound is nickel carbonyl, Ni(CO)4
exposure to which has been through acci-
dental release to nickel-processing
workers. Acute nickel carbonyl poisoning
is clinically manifested by both
immediate and delayed symptomology.
With the onset of the delayed, insidious
symptomology there are constnctive
chest pain, dry coughing, hyperpnea,
cyanosis, occasional gastrointestinal
symptoms, sweating, visual disturbances,
and severe weakness. Most of these
symptoms strongly resemble those of
viral pneumonia.
The lung is the target organ in nickel
carbonyl poisoning in both man and
animals. The pathological pulmonary
lesions observed in acute human
exposure include pulmonary hemorrhage,
edema, and cellular derangement.
Patients surviving an acute episode of
exposure may be left with pulmonary
fibroses.
Chronic Effects of Nickel
Exposure
Dermatological Effects
Nickel dermatitis and other derma-
tological effects of nickel have been
documented in both nickel worker
populations and populations at large.
Originally considered to be a problem in
occupational medicine, the more recent
clinical and epidemiological reports
suggest that nonoccupational exposures
to nickel-containing commodities may
present significant problems to the
general populace. Nonoccupational
exposure to nickel includes nickel-
containing jewelry, coins, tools, cooking
utensils, stainless steel kitchens,
prostheses, and clothing fasteners.
Clinically, nickel dermatitis is usually
manifested as a papular or
papulovesicular dermatitis with a
tendency toward lichenification, having
the characteristics of atopic rather than
eczematous dermatitis. The hand eczema
associated with nickel allergy appears to
be of the pompholyx type, i..e., a
recurring itching eruption with deeply
seated fresh vesicles and little erythema
localized on the palms, volar aspects,
and sides of fingers.
A role for oral nickel in dermatitic
responses by sensitive subjects has
recently been described. Nickel-limited
diets in one clinical trial resulted in
marked improvement of hand eczema in
half of the subjects while in a second
study, nickel added to the diets of
patients appeared to aggravate the
allergic response. Further study of oral
nickel-nickel sensitivity relationships
should be conducted.
Nickel-containing implanted
prostheses may provoke flare-ups of
nickel dermatitis in nickel-sensitive
individuals. The extent of this problem
appears to depend on the relative ease
with which nickel can be solubilized from
the surface of the devices by action of
extracellular fluid.
The underlying mechanisms of nickel
sensitivity presumably include diffusion
of nickel through the skin and subsequent
binding of nickel ion.
Useful animal experimental models of
nickel sensitivity are few and have been
conducted only under very specialized
conditions.
Respiratory Effects
Noncarcmogenic effects of nickel in
the human respiratory tract mainly derive
from studies of nickel workers in certain
production or use categories who have
been exposed to various forms of nickel.
In the aggregate, assessment of available
human and animal data show two areas
of possible concern for humans: (1) direct
respiratory effects such as asthma, nasal
septal perforations, and chronic rhinitis
and sinusitis; and (2) increased risk for
chronic respiratory tract infections
secondary to the effect of nickel on the
respiratory immune system.
Endocrine Effects
A numberjaf effects of nickel on endo-
crine-mediated physiological processes
have been observed. In carbohydrate
metabolism, nickel induces a rapid
transitory hyperglycemia in rats, rabbits,
and domestic fowl after parental
exposure to nickel (II) salts. These
changes may be associated with effects
on alpha and beta cells in the pancreatic
islets of Langerhans. Nickel also appears
to affect the hypothalamic tract in
animals, decreasing the release of
prolactin. Decreased iodine uptake by the
thyroid has also been observed when
nickel chloride is inhaled or ingested.
Human endocrine responses to nickel
have been poorly studied, although
hyperglycemia has been reported in
workmen accidentally exposed to nick
carbonyl.
Cardiovascular Effects
Experimental and clinical observ
tions suggest that exogenous nickel
ion, and possibly endogenous nickel
has a marked vasoconstrictive action
coronary vessels. Recent studies sh<
that such action may be operative
patients with ischemic myocardial mji
and in burn patients. Whether excessi
nickel exposure in occupational
nonoccupational populations coi
exacerbate ischemic heart disease
enhance the risk of myocardial infarct
in subjects with coronary artery disec
is unknown but merits further study.
Reproductive and Developmen
Effects
Exposure to nickel has been showr
cause both reproductive a
developmental effects in expenmei
animals; however, such effects have
been noted in man.
Specific reproductive effects seer
male rats include degenerative chan
in the testis, epididymis e
spermatozoa. Limited studies in fen
rats and hamsters suggest an effect
embryo viability and the implanta
process. Such effects have been note
animals exposed to excess amount;
nickel. In contrast, it has bi
demonstrated that a deficiency of die
nickel can also lead to reproduc
effects in the form of reduced litter s
and decreased viability of newborn.
With respect to developmental toxi
nickel exposure of animals prio
implantation has been associated
delayed embryonic development
possibly with increased resorpti
Structural malformations have been n
in avian species exposed to nickel :
While similar malformations have
been seen in mammals, the data
been lacking in sufficient detail m<
determinations about signifiCt
difficult. Teratogenic effects of n
carbonyl in mammals have t
demonstrated in two rodent species.
Mutagenic Effects
Various inorganic compounds of r
have been tested for mutagenicity
other genotoxic effects in a variety c
systems. From these tests it appear
nickel may induce gene mutatioi
bacteria and cultured mammalian
however, the evidence is fairly we
addition, nickel appears to in
chromosomal aberrations in cul
-------
mammalian cells and sister chromatid
sxchange in both cultured mammalian
cells and human lymphocytes. However,
the induction of chromosomal aberrations
in vivo has not been observed. More
definitive studies are needed to
determine whether or not nickel is
clastogenic. Nickel does appear to have
the ability to induce morphological cell
transformations in vitro and to interact
with DNA resulting in crosslinks and
strand breaks. In aggregate, studies have
demonstrated the ability of nickel
compounds to induce genotoxic effects;
however, the translation of these effects
into actual mutations is still not clearly
understood.
Carcinogenic Effects
There is evidence both in humans and
animals for the carcinogenicity of nickel,
at least in some forms. The human
evidence of a cancer risk is strongest via
inhalation in the sulfide nickel matte
refining industry. This evidence includes
a consistency of findings across many
different studies in several different
countries, specificity of tumor site (lung
and nose), high relative risks, particularly
for nasal cancer, and a dose-response
relationship by length of exposure. There
are also animal and in vitro studies on
iickel compounds which support the
concern that nickel, at least in some
orms, should be considered
;arcinogenic. The animal studies have
employed mainly injection as the route of
exposure with some studies using
nhalation as the exposure route. While
he majority of the compounds tested in
he injection studies have caused tumors
it the injection site only, nickel acetate,
when tested in strain A mice, and nickel
:arbonyl, at toxic levels, have also
:aused distal site primary tumors. The
elevance of injection site, only tumors in
inimals to human carcinogenic hazard
'ia inhalation, ingestion, or cutaneous
•xposure is uncertain. Orally, in animals,
hree low-dose drinking water studies and
me diet study with soluble nickel
ompounds have not shown any increase
i tumors. Thus, nickel at least in some
orms, should be considered
arcinogenic to humans via inhalation,
'hile the evidence via ingestion is
(adequate.
Based on analysis of all the available
ata there are only three compounds or
lixtures of nickel compounds that can
urrently be classified as either Group A
known human carcinogens) or B
irobable human carcinogens), according
the Environmental Protection Agency's
lassification scheme for evaluating
carcinogens . Nickel refinery dust from
pyrometallurgical sulfide nickel matte
refineries is classified as Group A. The
fact that nickel subsulfide is a major
nickel component of this refinery dust,
along with the evidence from animal and
in vitro studies, is sufficient to conclude
that nickel subsulfide is also in Group A.
While there is inadequate evidence from
epidemiologic studies with regard to
evaluating the carcinogenicity of nickel
carbonyl, there is sufficient evidence
from animal studies to classify it as
Group B2. The carcinogenic potential of
other nickel compounds remains an
important area for further investigation.
Some biochemical and in vitro
toxicological studies seem to indicate the
nickel ion as a potential carcinogenic
form of nickel and nickel compounds. If
this is true, all nickel compounds might
be potentially carcinogenic with potency
differences related to their ability to enter
and make the carcinogenic form of nickel
available to a susceptible cell. However,
at the present time, neither the
bioavailability nor the carcmogenesis
mechanism of nickel compounds is well
understood.
Quantitatively, several data sets from
nickel refinery workers provide sufficient
exposure-response information both for
testing model fits and for estimating
incremental unit cancer risk. While the
data partially support the use of both the
additive and multiplicative excess risk
models, neither is entirely satisfactory.
Using both models and four data sets, a
range of incremental unit risks from 1.1 x
10-5 (jig/m3)-i to 46 x 1(M (ng/m3)-i has
been calculated. Taking the midpoint of
this range, the quantitative incremental
unit risk estimate for nickel refinery dust
is 2.4 x 1Q-4 (ng/m3)-i; the quantitative
unit risk estimate for nickel subsulfide,
the most carcinogenic nickel compound
in animals is twice that for nickel refinery
dust. Comparing the potency of nickel
subsulfide to 55 other compounds which
the Environmental Protection Agency has
evaluated as suspect or known human
carcinogens, nickel subsulfide would rank
between the second and third quartiles.
Other Toxic Effects
Except for acute fatal exposures to
nickel carbonyl, nickel compounds
appear to possess low general neurotoxic
potential. Lesions observed in neural
tissue by nickel carbonyl include diffuse
punctate hemorrhages, neural fiber
degeneration, and marked edema.
Nickel subsulfide, when administered
intrarenally to rats, provokes a
pronounced, dose-dependent erythro-
cytosis associated with erythroid hyper-
plasia in bone marrow.
The effects of nickel chloride on the
cellular and humoral immune responses
of mice have been studied. Of particular
note is the ability of nickel chloride to
suppress the activity of natural killer cells
within 24 hours of a single intramuscular
injection. Such cells are thought to be
one of the first lines of nonspecific
defense against certain types of infection
and tumors.
Nickel as an Essential Element
There is a growing body of literature
which establishes an essential role for
nickel, at least in experimental animals.
One key criterion for element
essentiality-existence of specific nickel-
deficiency syndromes—is reasonably
satisfied for nickel. Various researchers
have shown different systemic lesions in
various animals deprived of dietary
nickel. Nickel deprivation has an effect on
body weight, reproductive capability, and
viability of offspring and induces an
anemia through reduced absorption of
iron. Both antagonistic and synergistic
interactions of nickel with various
compounds have been noted to affect
nutritional requirements.
Nickel also appears to be required in
several proteins and enzymes. Jack bean
urease (and possibly rumen microbial
urease) has been shown to be such an
enzyme. Recent studies on the activation
of the calmodulin-dependent phospho-
protein phosphatase, calcineurin,
suggests that nickel II may play a physio-
logical role in the structural stability and
full activation of this particular enzyme.
Further information in support of nickel
as an essential element is the apparent
existence of a homeostatic mechanism
for regulating nickel metabolism and the
existence of nickel proteins in man and
rabbit. Although the evidence for the role
of nickel in human physiology is not
conclusively established, the transitory
rise in circulatory nickel observed shortly
after parturition has been linked to a
possible role in control of atonic bleeding
and placenta! separation.
Populations at Risk
Among various subgroups of the U.S.
population who may be at special risk for
adverse effects of nickel are those who
have nickel hypersensitivity and suffer
chronic flare-ups of skin disorders with
frank exposure. Within this category
would be individuals predisposed to
-------
sensitization to nickel by virtue of familial The extent to which nickel in inhaled exposing the conceptus to nickel. Ther
history. In terms of the extent of nickel cigarette smoke is a cofactor in the is no information at present that nicki
exposure among hypersensitive individ- demonstrated association of smoking exposure in utero under conditions <
uals, women who are housewives seem with various respiratory disorders is not nickel exposure encountered by pregnai
to be at particular risk. However, no data defined at present, since various studies women in the U.S. population leads '
base exists by which to determine the have presented conflicting information. adverse effects.
prevalence of nickel hypersensitivity in Nickel crosses the placental barrier in
the general U.S. population. animals and apparently in man, thus
------- |