External Review Draft
February, 1975
SCIENTIFIC AND TECHNICAL ASSESSMENT REPORT
ON
NICKEL
NOTICE
This document is a preliminary draft. It
has not been formally released by EPA and
should not at this stage be construed to
represent Agency policy. It is being
circulated for comment on its technical
accuracy and policy implications.
U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
WASHINGTON, D. C. 20460
-------
TABLE OF CONTENTS
BO NOT QUOTE OR C1JE
1 INTRODUCTION- -- 1- 1
2 SUMMARY AND CONCLUSIONS- --- - 2- 1
2.1 SUMMARY- - 2- 1
2.2 CONCLUSIONS 2- 8
3. CHEMICAL AND PHYSICAL PROPERTIES— 3- 1
4. MEASUREMENT TECHNIQUES — 4- 1
4.1 AIR --- 4- 1
4.1.1 Air Sampling 4- 1
4.1.2 Preparation of Sample 4- 1
4.1.3 Analysis 4-"2
4.2 WATER - 4- 9
4.3 BIOLOGICAL MATERIALS 4- 9
4.3.1 Sample Preparation 4- 9
4.3.2 Analysis 4-11
4.4 NICKEL CARBONYL 4-12
4.5 REFERENCES FOR SECTION 4—— - - - 4-14
5. ENVIRONMENTAL APPRAISAL 5- 1
5.1 ORIGIN AND ABUNDANCE - - 5- 1
5.1.1 Natural Sources — - - 5- 1
5.1.2 Man-Made Sources 5- 2
5.2 CONCENTRATIONS— 5-10
5.2.1 Air - 5-10
5.2.2 Water 5-18
5.2.3 Soil - - 5-19
5.2.4 Plants— - — 5-23
5.2.5 Microorganisms — 5-23
5.2.6 Animals-- 5-27
5.3 TRANSFORMATION AND TRANSPORT MECHANISMS -- 5-35
5.3.1 Natural Mechanisms 5-35
5.3.2 Man-Made 5-47
5.4 REFERENCES FOR SECTION 5 5-52
6. ENVIRONMENTAL EXPOSURE- - 6- 1
6.1 MULTI-MEDIA EXPOSURE 6- 1
6.1.1 Ambient Air 6-1
6.1.2 Water— 6- 3
6.1.3 Food 6- 5
6.1.4 Soils 6- 6
6.1.5 Occupational 6- 9
6.2 RECEPTOR RISKS 6- 9
6.3 REFERENCES FOR SECTION 6 6-12
-------
DRAFT
NERC/Cinn "~ ' V^'Tt Ctt CITE
Albert J. Klee
Gordon Roebeck
OAQPS
John Bachman
-------
PREFACE nn Mr* r;:T£ 0$ ?.!?!*
Although this report is issued in the Scientific and Technical
Assessment Report Series, it differs in several respects from the comprehensive
multi-media format that the Series will usually have because it was
nearly completed prior to the creation of the STAR series in August
1974.
This document was prepared by a task force convened at the direction
of Dr. John F. Finklea, Director, U. S. Environmental Protection Agency,
National Environmental Research Center (NERC), Research Triangle Park
(RTP), N. C. Assembly, integration, and production of the report was
directed by the Special Studies Staff, NERC/RTP. The objective of the
task force was to review and evaluate the current knowledge of nickel in
the environment as related to possible deleterious effects upon human
health and welfare
Information from the literature and other sources has been considered
generally through March 1974.
A report prepared for the U. S. Environmental Protection Agency
(EPA) by a National Academy of Sciences' Panel on Nickel of the Committee
on Medical and Biological Effects of Environmental Pollutants served as
a primary reference for this report.
The following persons served on the task force:
From NERC/RTP:
James R. Smith James B. Upham
D. Bruce Harris Thomas E. Waddell
R. Don Zehr J.H.B. Garner
Diane Fogleman Michael D. Waters
Arthur I. Coleman Ronald Bradow
Marijon M. Bufalini Edward Faeder
Joseph F. Walling
-------
This document Is a preliminary draft. H
has not been formally released by EPA
and should not at thfs stage be construed
1. INTRODUCTION to torment Agency policy. It IB being;
circulated for comment on its technical
accuracy and policy implications.
The purpose of this document is to summarize our current knowledge
of nickel in the environment, and the effects of nickel compounds upon
human health and welfare; and to assess this knowledge base with a view
toward the need for control of the activities of man which impact upon
the nature and distribution of nickel in the environment. It was not
intended that this document constitute an in-depth scientific summary
of biological effects. Such an in-depth summary has been prepared by
the National Academy of Science Panel on Nickel and was used as a basic
reference for this report. Primary emphasis is placed on those aspects
of the problem which are considered most important relative to the de-
cision making processes which are the responsibility of the Environmental
Protection Agency. The major concerns of this document are the transformation
and distribution processes which govern spatial and temporal changes in
the concentration of various nickel compounds in air, water, soil, and
biota. Particular attention is given to those processes and interface
problems which may provide the insight necessary for prudent decisions
regarding management and control. These include measurement and analytical
techniques necessary for monitoring environmental loading and man's
contribution thereto, transport and removal processes within and between
environmental media, mechanisms and risks of exposure and response, un-
desirable effects, and control technology and remedial action. An attempt
is made to establish a set of decision-making criteria and a systematic
framework for evaluating alternative control actions.
1-1
-------
I >•«.
r1.') f '• ••••'•'•' •"••-..
2.0 SUMMARY AND CONCLUSIOW AX?;\»--./':''"•'•"".•'
2.1 SUMMARY ':'; tft ,'-,•,:/;
w;£
Nickel is a natural component of the earth's crust where it is
found in igneous rock and in shale. Large nodule deposits with a high
nickel content have been found on the ocean floor. The average farm
soil contains 0.003 percent or more of nickel although concentrations
vary widely from area to area.
Nickel is found in all coals and is also found in crude oil.
Sea water has a nickel content ranging from 0.1 to 0.5 yg/liter, while
the mean concentrations in the waters of the major river basins of the
United States range from 3 to 56 yg/liter.
Little is known concerning natural atmospheric sources of nickel.
The forms of nickel in air and their reactions have not been extensively
studied. It would be expected that nickel would be present predominately
in particulate form.
Nickel has been found in material filtered from the air throughout
the United States. Urban values are generally higher than nonurban with
the highest values generally being in the industrialized cities of the
East. The highest nonurban values in the East exceed some urban values
found in the western parts of the nation.
Clear annual average trends are not apparent in the data presented.
Seasonal variations are observed at some but not all sites.
Limited data on particle sizes associated with nickel are available.
They suggest that less than half of the nickel is to be found in the
smaller particulates, 1 micrometer or less in diameter.
2-1
-------
np/uf
DO NOT OJCTFn? r;rc
•• •• **••<.• i i L
The largest source of nickel emissions to the air is the combustion of
fossil fuel; mining and metallurgical nickel products are additional sources.
Nickel emissions from power generating plants using pulverized coal is
concentrated in particulate matter of less than one micrometer in diameter
and, therefore, is respirable. Use of oil presents a similar hazard
since 90 percent of such particulate emissions are less than one micrometer.
Diesel engine exhausts and exhausts from cars with catalysts are
possible mobile sources of nickel emissions.
The average nickel concentration in drinking water obtained from a
survey of community water supplies was 4.8 yg/liter. Among the'common
foods for which the nickel content has been ascertained, the following
have relatively high levels of Mi: baking powder, 13.4 yg/g; orange
pekoe tea, 7.6 y.g/g; buckwheat seed, 6.5 yg/g; cocoa, 5.0 yg/g; gelatin,
4.5 yg/g; black pepper, 3.9 yg/g; mushrooms, 3.5 yg/g; cabbage, 3.3 yg/g;
red kidney beans, 2.6 yg/g; oats, 2.4 yg/g; and shortening, from 2.0 to
6.0 yg/g.
The nickel content of plants is usually less than 1 ppm. Plants
whether they are used for food or not, may be exposed to nickel from the
air, in the water or in the soil. Aerial exposure occurs largely due to
nickel dust from industrial processes and motor vehicles being deposited
on vegetation and the soil.
Nickel concentrations in soil in industrial areas were 1.4 times
higher than soil in residential zones and levels around airports were
-------
t.' • w 11 i
NOT 0!i-*>Tr AD PITC
higher than either the industrial bVV&To^ritf a^NsiMnlst Agricultural
soils were found to have concentrations slightly above residential
levels.
Phosphate fertilizers and sewage sludge may raise soil concentrations
of nickel when added to the soil. Fertilizers have shown nickel con-
centration ranges from 3.0 to 38.0 vg/g; sewage sludge <32 to 2900 yg/g
dry weight.
Fallout from automobiles may increase the nickel content of soil
along highways
Exposure of terrestrial plants to nickel occurs chiefly through the
roots. Nickel can only enter the plant when in soluble form and is
dependent on soil moisture, pH, the solubility and chemistry of nickel,
chemical binding, and the presence and competition of other elements.
Routes of exposure of man and other animals to nickel are essentially
the same, with differences, perhaps, in relative magnitude of importance.
The routes of exposure of animals in order of importance are: ingestion,
inhalation, absorption through the skin, and parenteral administration.
Exposure of animals other than humans to nickel is dependent on
their choice of food plants. In the case of domestic animals, it will
be principally through the nickel present in pasture grasses and feed
grains.
It has been suggested that mammals possess mechanisms that limit
intestinal absorption of nickel. Feeding experiments using dogs suggest
that 10 percent of soluble nickel is absorbed. Higher absorption in
dogs than in man might be expected due to the relatively low pH of the
canine gastric juices.
-------
ui) nor QUOTE OR CITE
It has been estimated that the nickel content of food and water
ingested by human beings ranges from 300 to 600 yg per day; however,
most of the nickel content of the diet passes through the gastrointestinal
system unabsorbed.
The highest concentration of nickel in the body is in the skin.
The estimated quantity of nickel inhaled by a resident of one of the
cities having the highest measurements of nickel in ambient air are 2.36
yg/day in New York City, or 13.8 yg/day in East Chicago. The average
daily intake of nickel by urban residents is 2 to 14 yg/per day, depending
upon the season and the location.
The amount of nickel inhaled by smokers of cigarettes has been
estimated: A smoker who consumes 40 cigarettes per day inhales a maximum
of 14.8 yg of nickel per day from this source.
.Nickel is found in normal human serum and in rabbit serum in three
forms; bound to albumin, bound to an a-macroglobulin termed "nickeloplasmin,"
and in ultrafilterable complexes. The latter complexes may function.as
carriers for the extracellular transport and renal excretion of nickel,
since certain of them are also present in urine.
Nickel has also been shown to bind to isolated DNA, RNA, and protein
as well as to their monomeric subunits.
Nickel is known to inhibit a number of enzymes, notably 5-nucleo- •
tidase and ATPase, the latter being an essential enzyme in energy transfer
reactions.
-------
DRAFT
In its effect on nervous and contract! 1§)Q j\|QJ OUOTE OR CITF
In its effect on nervous and contractile tissue, nickel appears to
compete with and to imitate the effects of calcium, causing essentially
a prolonged action potential and an uncoupling between membrane activation
and muscle contraction. Few effects of nickel on the central nervous
system have been reported.
Nickel meets certain criteria for essentiality as a micronutrient
by virtue of its: demonstration in the fetus or newborn, homeostatically
regulated concentration, pathophysiologically altered metabolic pool,
presence as an integral part of an enzyme, and prevention or reversal of
a deficiency state. With regard to these criteria, it has been demonstrated
that nickel can cross the placenta (man), that the kidney processes an
active excretory mechanism for nickel (man), that nickel concentrations
in serum are significantly increased following myocardial infarction
and after stroke and burns (man), and that perimitochondrial dilation of
rough endoplasmic reticulum may be an early sign of hepatocyte degeneration
in nickel deficiency (chicks).
Nickel salts are relatively non-toxic by the oral route but quite
toxic when administered intravenously. Less information is available
regarding toxicity by inhalation, except for nickel carbonyl which is
extremely toxic. It is known, however, that nickel oxide displays
moderate retention in the hamster lung. The pulmonary parenchyma is the
target tissue for nickel carbonyl regardless of the route of exposure.
Interstitial edema and epithelial hyperplasia proceed severe intra-
alveolar edema and death. Pathologic findings in other organs are
generally less severe.
-------
OH MPT OH*-): Qp PJTJT
It has been suggested that the acute toxicity of nickel carbonyl
may result, in part, from inhibition of the utilization of ATP as previously
mentioned. The principal concern over nickel carbonyl is related to its
carcinogenicity rather than its toxicity.
The carcinogenicity of nickel compounds, in general, appears to be
inversely correlated with their solubility in aqueous media. The stronger
carcinogens, Ni^S^ and NiO, are practically insoluble in aqueous solutions,
while the non-carcinogens, NiSCL, NiClp, and NiNH.SCL are highly soluble.
NiS, which has low solubility', is an exception, exhibiting low carcino-
genicity, as is NHCpH-CLK, which is relatively soluble, in showing
moderate carcinogenicity. Although there has been considerable speculation,
the exact mechanisms whereby nickel compounds exert their carcinogenic
actions are incompletely understood. The mechanisms whereby nickel
enters target cells are undoubtedly important in the etiology of nickel
carcinogenesis. In the cases of nickel carbonyl and nickelocene, it
appears that the intact compounds pass across the cell membrane without
metabolic alteration. With other, rather insoluble inorganic nickel
compounds, such as nickel subsulfide, a diffusible intermediate complex
appears to be involved in the intracellular transport of the metal.
2+
Once entry into the cell is gained, the biochemical effects of the Ni
ions may become an important aspect of nickel carcinogenesis. The
inhibitory effects of nickel compounds, particularly nickel carbonyl, on
RNA synthesis are particularly noteworthy.
There is some evidence that nickel compounds may interact synergistically
with polynuclear aromatic hydrocarbons in reducing the time required
for tumor production.
-------
ir i
DO NOT QUOTE 01? CITE
Nickel dermatitis, "nickel itch," occurs among nickel miners and
workers in smelters, refiners and the nickel-plating industry. Currently,
nickel dermatitis is being reported by non-industrial populations who
came in contact with the metal in their every day activities.
Nickel has not been demonstrated to be an essential element for
plant growth. Lack of nickel in the soil does not appear to be detrimental,
while an overabundance is.
Dwarfing or growth repression, chlorosis and death all occur from
overabundance of nickel.
Toxicity of nickel usually appears in plants when concentrations
are 3 ppm or higher.
Tolerance mechanisms may be "external" or "internal" in nature.
Tolerant plants are metabolically different from normal plants. They
also have mechanisms which concentrate nickel in the epidermis and
sclerenchymatous tissue.
Most microorganisms are sensitive to nickel compounds; however, a
few exist which are capable of oxidizing nickel sulfides. These bacteria
are found on mine drainage areas.
Inorganic nickel salts have been used as fungicides.
Landfill 'leachates contain varying amounts of nickel, and have the
porential for contaminating drinking water supplies. Nickel can also
enter the environment through the incineration of municipal solid wastes,
but the quantities reported are small. The nickel content of composts made
from such wastes is also relatively small. Continued recycling of municipal
incinerator residue for scrap steel may result in a buildup of nickel
(and other metallic impurities.
Control technology for the disposal of nickel-bearing materials in
landfills involves detailed site planning and engineering.
2-1
-------
UKAFT
2.2 CONCLUSIONS DO MOT QUOTE OR CITE
The following are the more significant conclusions derived from the
currently available information regarding nickel in the environment:
o Nickel has been found in air throughout the country. Urban
concentrations are generally higher than nonurban with the highest values
generally being found in the industrialized cities of the East. Some
season variations have been noted at some sites, but annual trends are not
obvious.
o It appears that less than half of the atmospheric nickel is
associated with fine particulates; however, data on particle size is
limited.
o The chemical reactions, chemical forms, residence time, ultimate
fate and the transformation and transport of nickel-containing particles
are not known.
o By far the largest source of atmospheric nickel is the combustion
of fossil fuels. Particulate matter in the respirable range (>/yg) is
emitted from the burning of pulverized coal and from the combustion of oil.
o The use of nickel-containing catalysts may add to the atmospheric
loading of nickel.
o The extent to which the nickel concentrations present in ambient
air pose a hazard for human health is at present unknown.
o Ingestion is the chief route of exposure to nickel for humans
not exposed occupationally. Most of the ingested nickel is excreted in
the feces.
-------
LWA1I" I
P'imT OR
o Food from plants growing in normal agricultural soils do not
constitute an important source of nickel exposure to humans.
o The nickel-containing stainless steels used for food processing
equipment are thought to dissolve only minute amounts of metal, "trace
quantities having no pharmacological significance."
o Except for the potential toxicity to crop producing plants, there
is little evidence available to indicate that nickel contamination of
soils is a critical problem. There are many published accounts of nickel
toxicity to selected crops. Soils near nickel mining areas can be
expected to contain toxic levels of nickel. Sewage sludge is also
a potential significant source for nickel contamination of soils, as
are industrial sludges containing nickel.
o The movement of nickel through biological food chains has not
been well documented.
o Landfill leachates have the potential for contaminating drinking
water supplies with nickel, therefore good landfill management is
important.
o The incineration or composting of municipal solid waste does not
constitute a major nickel pollution problem.
o Very little is known about the chemistry of nickel and its
compounds in seawater, however, it appears that the concentration factor of
nickel is among the lowest in the transition metal groups.
o The probability of exposure to nickel carbonyl, the most toxic
of all known organic nickel compounds, is limited primarily to cases of
occupational exposure.
-------
NOT C'fOiE OP r,rr
6 A smoker who consumes two packages of cigarettes per day may
inhale 1-5 yg of nickel per year, 84 percent of which may be nickel
carbonyl.
o The principal concern over nickel carbonyl is over its
carcinogenicity rather than its toxicity. The exact mechanisms whereby
nickel compounds exert their carcinogenic actions are,incompletely
understood.
o There is no evidence to indicate that the risk of the general
population to exposure to nickel through inhalation of ambient air or
oral intake through food and water is cause for concern.
o Nickel hypersensitivity due to contact with the metal is quite
common among the nonindustrial population, particularly women; however
the true incidence among the general population is unknown. The capacity
of nickel to act as a skin sensitizer is also unknown.
2. -ID
-------
UKAFT
3,; CHEMICAL AND PHYSICAL PROPERflflsNOT QUOTE OR CITP
Nickel is a silvery-white metal that is hard, malleable, and ductile.
It has an atomic weight of 58.71, a specific gravity of 8.9, a melting
point of 1455°C, and a boiling point of 2900°C. It is insoluble in both
hot and cold water but soluble in dilute acids. There are five isotopes
of nickel, 58, 60, 61, 62, and 64 which occur in natural abundance of
67.88, 26.23, 1.19, 3.66, and 1.08 percent respectively. The most
common valences nf nickel are 0 and 2 ? but the element mav form comnounHs
with more uncommon valences as 1", 1 , 3 , and 4". Nickel is highly
magnetic and is not oxidized under ordinary conditions.
Nickel is not found in the free state in nature. It occurs, along
with iron, as an alloy. The most important ores are pentlandite, a
sulfide of iron and nickel, and garnierite, a hydrated magnesium-nickel
silicate of variable composition. A major producing area for nickel is
Ontario, Canada. Other producing areas include Cuba, New Caledonia, the
Scandinavian countries, South Africa }and Russia.
The process used most extensively for obtaining pure metallic
nickel involves separation of the sulfides of nickel, copper, and iron
by selective flotation. After separation, the nickel sulfide is con-
verted to the oxide by roasting, and the oxide is reduced with carbon
affording approximately 96 percent pure metallic nickel. It is then
cast into huge anodes and refined electrolytically in a nickel (II)
sulfate bath. The nickel which deposits on the cathode is 99.98 percent
pure.
3-1
-------
LHW I
In combination, nickel exhibits an oxidation state of +2 almost
exclusively. One notable exception is tetravalent nickel in the dioxide,
NiCL a black anhydrous substance formed by the oxidation of nickel (II)
salts in alkaline solution. Soluble nickel salts are prepared from
nickel (II) oxide (NiO). Nickel (II) sulfide is produced as a black
I
precipitate by the action of ammonical sulfide solutions upon nickel
(II) salts. This compound exists in at least two crystalline modifications
of different degrees of solubility in mineral acids; this property is of
value in the analytical separation of the element.
Because of its hardness, resistance to corrosion, and high
reflectivity when polished, nickel is widely used in the plating of
iron, steel, and copper. It is also a constituent of many important
alloys. Monel metal (Ni, Cu and a little Fe)^ is used as a corrosive
resistant alloy. Permalloy (Ni and Fe)> is remarkably permeable to the
magnetic field. It is used in instruments for the electrical transmission
and reproduction of sound. German silver is a nickel-zinc-copper alloy.
Nickelchrome and chromel are alloys containing nickel, iron? and chromium;
they are resistant to oxidation at high temperatures and shew high
electrical resistance at high temperatures, so are used in electrical
heating units such as stoves, pressing irons, and toasters. AJ^jinJco
contains aluminum, nickel, iron, and cobalt. Platinite and invar are
nickel alloys which have the same coefficient of expansion for "seal in"
wires through glass, such as those in electric light bulbs. Nickel
coins contain 75 percent copper. Finely divided nickel is used as a
catalyst in the hydrogenation "of oils. .
3-2
-------
*•"» w
4. MEASUREMENT TECHNIQUES
4.1 AIR
4.1.1 Air Sampling
Air pollutants containing nickel are usually in particulate form.
Samples can be collected by means of high volume samplers, sequential
tape samplers, electrostatic precipitators, scrubbers, impingers, or
impactors. The selection of filter material is made to minimize probable
interference with the method of measurement.
4.1.2 Preparation of Sample
Particulate nickel collected on paper, fiberglass, or Teflon filters
as well as on impingers can be dissolved with nitric acid, the excess
nitrogen oxides removed by boiling, and the solution made up to volume.
Three of the methods to be described require no prior chemical preparation
of the sample.
The available analytical methods for nickel are based upon the
techniques listed below:
o Atomic Absorption Spectrometry
o Spectrophotometry with dimethylglyoxime or other color regeants
o Polarography
o Anodic Stripping Voltammetry
o Optical Emission Spectroscopy
o Ring Oven
o X-Ray induced Fluorescence
o Neutron Activation Analysis
The last two require virtually no chemical separation nor preparation
of the sample prior to measurement. Economic considerations,
4-1
-------
calls for multiple elements and many samples. The ring oven is a simple,
inexpensive device whose use requires no prior treatment of the collected
sample.
4.1.3
DO. NCT QUOTE OR CITE
4.1.3.1 Atomic Absorption— Atomic absorption (AA) spectroscopy is the most
popular technique for metal s analysis and serves well for the determination
of nickel in solution. In order to adapt it to the increased sensitivity
demand of water samples and some biological samples, concentration techniques
(either solvent or chelation) are used. AA spectroscopy,
involves dissociating the element of interest into an un-ionized,
unexcited ground state. In this condition, the element can absorb
radiation at discrete narrow emission lines provided by a hollow cathode
lamp, which contains neon or argon at low pressure- and has a cathode of
the element sought. The intensity of absorption measures the element
present. The resonance line for nickel is 232 nm.
Background absorption is a problem when nickel is measured by AA.
The absorption occurs when appreciable concentrations of sample solvent,
such as ethyl propionate or methyl isobutyl ketone, are aspirated into the
flame. This background is measurable at 232 nm.
The nickel analysis will fit into the scope" of the AA technique
with a modicum of effort. Fifteen, elements can be analyzed in about 30
minutes, not including sample preparation. A tentative method of
analysis for nickel in atmospheric particles has been proposed by Kneip
et al.1
2
A solvent-extraction method by Sachdev and West can be used to
isolate nickel from interferences in aqueous solution and concentrate it
as well. A mixed ligand system containing 0.1 percent dithizone, 0.75
percent 8-quinolinol , and 20 percent acethyl acetone in ethyl
4-2
-------
propionate is used. The extraction is carried out at pH 6 +_ O.I
with ammonium tartrate. The organic extract is aspirated into the*x*
air-acetylene flame. It is claimed that concentrations as low
as 0.004 ppm can be determined. *^
3 *?"
The above method has been modified by Dharamarajan and West
to apply directly to air samples collected on membrane or fiberglass
filters. In this modified method a portion of the filter with sample
is moistened with 2 ml of 15 percent ammonium acetate solution, then
ten milliliters of ligand mixture are added, and the organic extract
is aspirated.
4.1.3.2 Spectrophotometry—Spectrophotometry with color forminq reagents is a
technique with a long history. It is used most frequently in water analysis
and is not as fast as AA even on a routine basis. The spectrophotometric method ft
measuring nickel is based upon the formation of dimethylglyoxime complex. It
is one of the best known colorimetric methods. The nickel compound
is formed in citrate solution. Oxidation with bromine water intensi-
fies the color. The complex is extracted from aqueous solution with
chloroform. Cobalt or copper interference is removed with an ammonia
wash and manganese interference is thwarted with hydroxylamine
hydrochloride. The absorbance is measured at 445 nm. Sensitivity
o
of the procedure is estimated to be 0.0042 mg/cm .
4
Forester and Jones report that
-------
D
O HOT QUOTE CR CITE
4.1.3.3 Po1arography--The polarographic method relies on the diffusion
current produced from the oxidation or reduction process which occurs at
an electrode with renewable surface. A dropping mercury electrode
is typical of the type used. The potential required for the process
is characteristic of the species in solution. This makes it possible
to resolve several ions in solutuion by varying the applied potential.
The principle underlying the use of polarography for quantitative
analysis is that the diffusion current is directly proportional to
the concentration of sample ions if other pertinent variables are
kept constant.
A polarographic method for nickel reported by West and Dean
uses sodium fluoride as the background electrolyte. Sodium fluoride
eliminates interference by forming stable complexes with iron, cobalt,
and copper. Evaluation of the measurement can be made from a standard
curve of current versus concentration or by adding a nickel standard
to a second aliquot of sample and testing it with the polarographic
procedure.
Although the above method is an example of the classic polaro-
graphic technique, it falls short of the sensitivities obtainable
by the spectrometric methods. Polarographic techniques can be
improved by the use of pulse polarography.
D. D. Gilbert described a pulse method for measuring nickel and
vanadium, that used the differential mode of operation. Good agreement
with colorimetric and emission spectroscopic procedures was demon-
strated. Concentrations of 0.045 yg/ml could be determined.
-------
AlftT O1 rv*'r" '"•'"> 'MT*
NOT QjJiL wS JiE
Pulse polarography compares favorably with atomic absorption
in sensitivity limits but is not as fast if only one or two elements
are to be determined.
4.1.3.4 Anodic Stripping voltammetry--Anodic stripping voltammetry
'i
(ASV) is recommended for its sensitivity. Pulse techniques are
known and sample volumes as small as 2 ml are sufficient. The desired metals are
plated out of solution onto an electrode. Then, the electrode potential
is varied linearly in the anodic direction. This causes the metals
to be stripped off in turn from the electrode. The dissolution curve,
amperage versus voltage, shows a current peak as each metal species
goes into solution. As long as the voltage is changed at a fixed
rate, the curve is also amperage versus time. Thus, the area under
the peak is a measure of nickel content. If the peak is sharp, its
height can be the measure. Calibration is made with standards.
The kinds of electrodes used are mercury pool and drop, mercury
film on inert metal, or inert metal, either platinum or gold.
Nicholson described a study which produced a set of analytical
conditions for ASV of nickel at solid electrodes. The solution con-
tained nickel in a complex ion (thiocyanate) in order to bring plating
and stripping reactions within a reasonable range of potential. Even
under such favorable conditions, mercury is oxidized at the stripping
voltage, masking the nickel current. Because of this, inert electrodes
of gold or platinum were used. Nickel concentrations as low as
-8
5X10" M (3 ppb) were determined. In order to produce measurable
currents, the plating-stripping times were increased for increasingly
lower concentrations.
-------
-• "\ WVT •"•'; "••"•- "•'• """."'£
l.: j |iv/ ! \ -< '»> t i~ '<--ii V- » U
4.1.3.5 Optical Emission $pectrometry'--In this technique, the sample
in solution is dispensed by rotating an electrode into the region
of a high voltage A.C. spark. The emission is analyzed, usually .
by diffraction grating. The metal concentration is determined by
comparing intensity of sample emission to intensity of emission for
standard solution at a selected wavelength.
o
R. J. Thompson has described the procedure which is used in
EPA for the spectroscopic determination of metals in atmospheric
particulate matter. The sample collection phase is carried out with
glass fiber or membrane filters. The sample is treated successively
by low temperature ashing and solution in a mixture of nitric and
hydrochloric acid. For the spectroscopic step, a Quantometer is
set to read out a number of metals.
Generally, atomic absorption is more precise, accurate, and
manipulatively simpler than optical emission spectrometry. The
detection limits of the two methods are not too far apart for nickel.
3 3
For atomic absorption it is 0.004 yg/m compared to 0.006 yg/m
Q
for optical emission spectroscopy. Thompson states that, for routine
analysis involving more than six metals, the use of emission spec-
troscopy becomes efficient.
4.1.3.6 Ring Oven Method—The ring oven is suited for the identifi-
cation and quantification of airborne particulate material. The
apparatus is simple and convenient for field use. The sample can be
collected by tape sampler or simply on filter paper. The dust spot
sample is centered on the heated ring of the oven. If the spot is
less than 22 mm in diameter it can be analyzed without prior sample
g
preparation. The procedure is reviewed by West.
-------
The lower limit of identification is 0.08 yg and the range of determination
is 0.1 to 1.0 yg nickel. There are no potential interferences. When the ring
o
d: zone is exposed to formaldehyde, the tetracyanonickelate complex, which is
O
I"— uJ formed during preliminary treatment of the spot with potassium cyanide is
UvV»» f^"»
'"
broken, thereby freeing the nickel to react with dimethyl-glyoxime.
••'•"
4.1.3.7 X-Ray'Fluorescence Spectrometry--X-ray fluorescence spectrometry con-
sists of irradiating the filter medium or impactor film containing the collected
particulate matter with X-rays. The method appears to be rapid, sensitive, and
capable of doing multicomponent analysis on a routine basis. However, large
numbers of samples are needed to justify the costs. Photons of sufficient
energy produce vacancies in the inner shells of the atoms of the
specimen and X-ray fluorescence results. These X-rays are detected,
sorted with respect to their energies, and elemental concentrations
are determined from intensity measurements.
Dzubay and Stevens described a new X-ray fluorescence spectrometer
system that incorporates secondary fluorescers of copper, molybdenum,
and terbium. A high resolution-low background silicon detector was
used. This system permits scanning for the elements in the periodic
system from aluminum and beyond. The analysis time was about fifteen
minutes.
The method is non-destructive but, in the case of particulates,
it is imperative that the particles be uniformly deposited on the
collection surface. The filter collector that is used should be very
low in impurity.
Giauque et al. have described the application of X-ray
fluorescence analysis to the characterization of aerosols. Hammerle
12
et al. studied X-ray fluorescence as a method for measuring elements
in atmospheric aerosols. They compared this method with neutron-
activation analysis and found greater sensitivity and precision with
-------
X-ray fluorescence. A comparison of their results for nickel show
0.47 +_ .03 yg when using X-ray fluorescence; 0.40 + .24 yg when
using neutron-activation; and at lower concentrations; 0.06 ± .02
with X-ray, and an undetectable amount with NAA. Either method is
best applied to scanning for groups of elements.
4.1.3.8 Neutron Activation Analysis—Neutron-activation analysis
(NAA) has found wide application for a number of years. In the past
it was necessary to separate the elements of interest to remove the
interferences of other elements. The field of instrument neutron-
activation analysis (INAA), in which no chemical separations are
performed, has been greatly extended by the development of lithium-
drifted Ge y-ray detectors. Ge (Li) detectors have much better
resolution than the sodium iodide (Tl) scintillation counters previously
used for X-ray spectrometry. This means that it is now possible
to resolve y-rays of many radioactive nuclides from complex mixtures
of activities.
The nuclides are identified by y-ray spectrometry. Gamma-ray
energies of most products of reasonable half life including nickel,
have been accurately determined.
The value of the technique lies in the ability to measure the
concentrations of a group of elements in one sample. The same sample
can then be used to measure additional elements by other methods.
The analysis can be largely automated and computerized for.
species emitting strong y-rays. If a computer is not available, manual
computation for long run irradiations as required for Ni would take
2 hours per sample for the group of elements.
4-S
-------
DRAFT
DO NOT QUOTE OR CITE
4.2 WATER
The techniques of atomic absorption spectrophotometry, polaro-
graphy, anodic stripping voltammetry, and ring oven are applicable
to the determination of nickel in water. The nickel concentration,
however, may be less than for air samples by a factor of a thousand.
If sample enrichment is necessary, the solvent extraction method of
2
Sachdev and West can be used or the chelation method of Malissa
and Schoeffman. The literature describes the chelation method as
auxiliary to atomic absorption spectrometry. Reference to use with
other methods has not been found.
X-Ray fluorescence analysis requires that the sample be dry-
deposited on plastic film. No reference has been found to the
14
evaporation of samples of water for deposition. Vassos et al.
describe a technique for preconcentration by electrodeposition of
nickel on pyrolytic graphite. After deposition, a thin disk was
cleaved from the electrode surface and analyzed by X-ray fluorescence.
Quantities determined were in the low ppm range. Since the recommended
deposition times exceed one hour, the method appears to be cumbersome.
4.3 BIOLOGICAL MATERIALS
4.3.1 Sample Preparation
The initial step with plant or animal tissue is often blending,
homogenizing, or grinding. In view of the very low concentrations
of nickel anticipated, however, use of the above apparatus with stainless
steel and nickel-plated parts is to be avoided. Pestles of glass
and teflon are available for grinding.
-------
It will be noted that with some techniques serum and urine
samples can be analyzed without chemical pretreatment.
Methods for the destruction of sample organic matter are of two
kinds; dry ashing and wet digestion. In dry ashing, the sample is
ignited in a furnace at about 500°C and the ash then dissolved in
acid.
Other dry ashing methods are the Schoeniger flash and the Parr
bomb. These techniques use oxygen under pressure in place of air
as oxidant. The dried sample is combusted in a closed system. A
newer technique has been developed by Gleit and Holland. 'A
radio frequency discharge is used to produce an oxygen plasma which
attacks organic matter at temperatures below 100°C. Biological tissues
have been ashed in this way. A commercial model is available, but
it is reported that ashing times exceed twenty-four hours. Hopefully,
later design will improve upon this undesirable characteristic.
In wet digestion, hot acids and oxidizing agents are used. -Frequently
used mixtures for the wet treatment are sulfuric, nitric, and
perchloric acids. The simpler mixture of nitric acid and hydrogen
peroxide is better suited for the analysis of tissues.
Dry ashing is recommended for its simplicity and because large
samples can be handled. Wet digestion is considered to be superior
in terms of speed, the low temperatures employed, and freedom from
loss by retention on container wall.
Because lower amounts of nickel are expected in biological samples
than in air samples, concentration may be needed to exploit the methods
of analysis described under air.
-------
_.
DONOTQ'JCTZC;?CiiE
Additionally, separation from the sample matrix may be necessary
to eliminate interferences. The extraction method of Sachdev and
2
West, which has been described earlier, can be used. Malissa and
13
Schoeffman have shown that ammonium pyrrolidine dithiocarbonate
(APDC) can be used to chelate with metallic elements at controlled
pH. At pH 2 through 4, nickel can be extracted with APDC into
methylisobutyl ketone along with cobalt. This technique is well
suited for samples that are intended for AA.
4.3.2 Analysis
Techniques applicable to nickel in biological samples are AA
spectrophotometry, pulse polarography, and anodic stripping voltam-
metry.
X-ray fluorescence could be used, but sample preparation is a
problem. Walter et al. reported on the analysis of biological,
clinical, and environmental samples using X-ray fluorescence. They
used a 3-Mev beam of protons from a Van de Graff accelerator to .
excite X-ray fluorescence rather than use primary X-rays as described
under air analysis. A wide range of elements including nickel was
determined.
Of interest at this point is their preparation of the sample
targets for analysis. Self-supporting materials, such as leaves
or insect wings, were attached to the sample holder with adhesive.
Non-selfsupporting samples, such as urine, blood, aqueous solutions,
or tissue sections, were deposited on plastic material which was stretched
over a graphite ring. The deposited liquid samples were dried in a
vacuum desiccator. Deposits, such as whole blood or ashed substances,
t-H
-------
00 HOT QiiOTE 08 c
tended to flake if not packaged with a cover of polyethylene or
polystyrene.
4.4 NICKEL CARBONYL
Because nickel carbonyl [Ni(COh] is a highly toxic gas, it has
received special attention with respect to sample handling and analysis.
At 60°C nickel carbonyl decomposes into carbon monoxide and nickel.
The nickel can be collected as particles. Nickel carbonyl can be
trapped in absolute ethanol and be kept at -78°C.
/ 18
The summary to be found in the National Academy of Sciences report
highlights the analytical problems of nickel carbonyl and describes
a gas chromatographic procedure for its determination. The procedure
is useful for monitoring industrial atmospheres, and is an aid in
diagnosing nickel carbonyl poisoning.
19
Brief et al. described a field method in which air samples
were collected in dilute hydrochloric acid. A yellow complex was
developed with a-furil dioxime. After extraction with chloroform,
the color was determined spectrophotometrically. The limit of
detection was estimated to be 0.002 ppm Ni(CO)4-
Brief et al. reviewed five other methods which are in use. In
one method the Ni(CO)4 is bubbled into a saturated solution of sulfur
in trifluoroethylene. The precipitated nickel sulfide is analyzed
by spectrograph in the ultraviolet region. The sensitivity limit is
0.0003 ppm Ni(CO).. In the second method, the sample is passed over
red mercuric oxide at 200 C. The mercury is determined spectrographically.
A parallel sample stream is oxidized to carbon dioxide and passed
over red mercuric oxide to liberate mercury.
-------
MH'OT n:i—'A "57?
hUi ^Js> i L. t'»i
-------
v-
9. West, P. W. The Determination of Trace Metals in Air. From:
Determination of Air Quality, G. Mamontov and W. D. Shults (ed).
Proceedings of A.C.S. Symposium on Determination of Air Quality
held in Los Angeles April 1-2, 1971. New York, Plenum Publishing
Corp., 1971, p. 313-142.
10. Dzubay, T. G. and R. K. Stevens. Applications of X-ray Fluorescence
to Particulate Measurements. (Presented at the Second Joint
Conference on the Sensing of Environmental Pollutants. Washington,
D. C. December 1973.
11. Giauque, R. D., L. Y. Goda, and N. E. Brown. Characterization of
Aerosols in California by X-Ray Induced X-Ray Fluorescence Analysis.
Environ. Sci. and Tech. 8>:436, 1974.
12. Hammerle, R. H., R. H. Marsh, K. Rengan, R. D. Giauque, and
J. N. Jaklevic. Test of X-Ray Fluorescence Spectrometry as a
Method for Analysis of the Elemental Composition of Atmospheric
Aerosols. Anal. Chem. 45:1939, 1973.
13. Malissa, H. and E. Schoeffman. Mikrochim, Acta. _, 187, 1955.
14. Vassos, B. H., R. F. Hirsch, and H. Letterman. X-Ray Microdeter-
mination of Chromium, Cobalt, Copper, Mercury, Nickel, and Zinc
in Water Using Electrochemical Preconcentration. Anal. Chem.
45:792, 1973.
15. Gleit, C. E. High Frequency Electrodeless Discharge System for
Ashing Organic Matter. Anal. Chem. 3_7:314, 1965.
16. Gleit, C. E. and W. D. Holland. Use of Electrically Excited
Oxygen for the Low Temperature Decomposition of Organic Substances.
Anal. Chem. 34:1454, 1962.
-------
^0 f.'
UJ It
17. Walter, R. L., R. D. Willis, W. F. Gutknecht, and J. M. Joyce.
Analysis of Biological, Clinical, and Environmental Samples
Using Proton-Induced X-Ray Emission. Anal. Chem. 46^:843, 1974.
18. Nickel, Final Report to U. S. Environmental Protection Agency,
Research Triangle Park, N. C. Contract No. 68-02-0542. National
Academy of Sciences, Washington, D. C. p. 331, 1974.
19. Brief, R. S., F. S. Venable, and R. S. Ajemian. Nickel Carbonyl:
Its Detection and Potential for Formation. Amer. Ind. Hyg.
Assoc. J. 26:72-76, 1965.
-AT
-------
DRAFT
•' DO NOT QUOTE OR CITE
5. ENVIRONMENTAL APPRAISAL,
5.1 ORIGIN AND ABUNDANCE
5.1.1 Natural Sources
Nickel is a natural component of the earth's crust (0.008 percent) --
the major portion being found in igneous rock (0.01 percent) with shale
(0.005 percent Containing the next largest amount . The earth's core
contains 8.5 percent nickel. Meteorites may contain 5 to 50 percent
nickel. Large nodule deposits with high nickel content have been found
on the ocean floor. Cobalt usually occurs with nickel, its presence
varying from a trace to ratios of one to ten.
The average farm soil in the United States contains 0.003 percent
or more of nickel, although the concentration in surface and subsurface
soils varies widely from area to area. This variability must be taken
into account when sampling to determine contamination from man-made
sources.
Nickel is found in all coals, but the content varies widely. The
average nickel content of coal from the United States is about 0.025
kg/MT in the mid-western states, 0.016 kg/MT in the eastern states, and
0.004 kg/MT in the western states. The average nickel concentration in
coal in the eastern and mid-western sections exceeds that found in the
earth's crust, hence coal could be considered as a source of nickel.
Nickel is also found in crude oil. The nickel content of crude oil
ranges from 0.000003 to 0.0064 percent. The nickel content of commercial
residual fuels ranges from nil to 0.00002 percent.
In the weathering process of rocks, nickel goes into the insoluble
minerals of the hydrolysates. Therefore, the nickel content of surface
or ground water is likely to be small unless it is due to man-made
-------
pollution. Nickel has been found in U. S. waters with a frequency of 16
percent and a mean concentration of 19 yg/liter. The nickel content of
sea water ranges from 0.1 to 0.5 yg/1.
Little is known concerning natural sources of nickel found in the
atmosphere. Nickel has been identified in volcanic gases and condensates
in a few instances. Nickel is found in detectable quantities in air in
both urban and non-urban areas. The data are not sufficient to determine
the contributions of natural sources to nickel in the non-urban atmosphere.
5.1.2 Man-Made Sources
5.1.2.1 Stationary Sources
The possible sources from which nickel may be emitted into the
atmosphere can be separated into four groups: mining, metallurgical
nickel products, and combustion.
Ontario, Canada is a major producer of nickel. Other producing
areas include Cuba, New Caledonia, the Scandinavian countries, South
Africa, Russia, Australia, and Indonesia. Mining is of minimal impact
in the United States since nickel mining and ore processing plants in
this country are few in number. One such plant is located in Huntington,
West Virginia. Air monitoring in 1968 to assess nickel concentrations
in Huntington and two other communities showed that ambient nickel
concentrations at the air sampling stations near the plant measured 1.2
yg/m of air, compared with an average nickel concentration of 0.04
3 2
yg/m at the six other sampling sites. No information is available
regarding health consequences in relation to these levels of nickel.
It is estimated that nickel mining operations emit about 2 MT of
S-:
-------
nickel per year.
3
DRAFT
00 MOT QUOTE OR CITE
Air monitoring in Sudbury, Ontario, a major nickel mining and
processing center, indicated ambient nickel concentrations ranged from
3 ^-.^
0.035 to 2.009 yg/m , depending upon the date of measurement. The
nickel concentrations in the Canadian cities of Toronto, Simcoe, and
St. Catherines had much lower ranges for the same dates of measurement
(every two weeks, January through August): Toronto - 0.006 to 0.107
•? 31
yg/m ; Simcoe - 0.004 to 0.066 yg/m ; and St. Catherines - 0.007 to
0.043 yg/m . There was no evidence presented which would indicate
whether nickel was hazardous to human health in Sudbury at the con-
centrations reported.
Most of the nickel reaching the atmosphere from ore processing
is particulate with the possibility that some gaseous nickel
carbonyl escapes from plants using the Mond process. The metallurgical
processing of ore to produce metallic nickel results in an estimated
4
emission to the atmosphere of 225 MT per year.
Most nickel is produced from sulfide ores. The process used
most extensively for obtaining pure metallic nickel involves separation
of the sulfides of nickel, copper, and iron by selective flotation.
After separation, the nickel sulfide is converted to the oxide by
roasting, and the oxide is reduced with carbon affording approximately
96 percent pure metallic nickel. It is then cast into huge anodes
and refined electrolytically in a nickel (II) sulfate bath. The
nickel which deposits on the cathode is 99.98 percent pure.
The primary use of nickel is by the metallurgical products
industry as an alloying or plating material. Some loss of nickel
S-3
-------
.'_/ i V M I '
*•••:? MOT U'OTEOR 0!TF
is expected during alloying operations. Where melting at high temperatures
is necessary, a metallic fume containing compounds of the melt is usually
evolved. In straight melting operations without oxygen lanr.ina, nickel
preferentially remains in the melt since it is chemically negative
relative to iron and, thus, stays out of the slag surface. Oxygen blows
stir up the melt and provide more opportunities for nickel to be lost.
4
Product sources have an estimated emission of 756 MT per year. Nickel
emissions from plating operations are more localized and constitute an
occupational health problem rather than an atmospheric load.
By far the largest source of nickel in the atmosphere is the
combustion of fossil fuels. Recent data estimate total nickel emissions
from coal use (primarily large power generating stations) at 3500 MT per
year and oil .consumption (residential and commercial heating and power
generating stations) at 7300 MT per year. It has been reported that
the nickel emissions from power generating plants using pulverized
is concentrated in particulate matter of less than one micrometer in
diameter and, is therefore, respirable. Oil emissions present a similar
hazard since 90 percent of such particulate emissions are less than one
ym.
The emission of nickel by stationary sources is summarized in Table
5.1.
5.1.2.2 Mobile sources—Nickel can be emitted from mobile sources by a
variety of mechanisms. Gas turbine high temperature components are
fabricated from nickel or high-nickel alloys and the spallation of these
materials can cause emission of nickel particles. Nickel and vanadium
-------
/--..-•. i\-r.T r-:i-"'iTr no PH"-'
... '..' /(>..; ! 1,/uJ I L lm U i i-
Table 5.1. EMISSION OF NICKEL TO THE ATMOSPHERE FROM STATIONARY'SOURCES,
17
Source
Nickel mining
Iron and Steel
Blast Furnace
Gray Iron Foundary Cupola
Ferro-Alloys
Blast Furnace
Electric Furnace
Non-Ferrous Alloys
Furnaces
Power Plant Boilers3
Coal8
Oil
Industrial Boilers
Coal
Oil
Residential /Commercial
Coal
Oil
Amount emitted,
MT
2
91
72
445
89
58
3,447
4,105
30
1,033
3
2,209
11,584
Percengage of total
nickel emissions
0.02
0.79
0.62
3.84
0.77
0.50
29.76
35.44
0.26
8.92
0.03
19.07
100.25
'EPA data'
5-5
-------
DO NOT QUOTL OR CHt
are the principal metallic components in crude oil where these metals
are bound as porphyrin derivatives. Concentrations of these elements
vary greatly with crude oil source but common levels for these elements
are 400 to 1000 ppm for vanadium and 10 to 100 ppm for nickel. Both
elements are increased in concentration in residuum because the metallo-
porphyrins are very stable, low vapor pressure components; typical
concentrations of nickel in the residuum are in the 100 to 1000 ppm
Q
range. The concentration of nickel in fuel oil and gasoline is lower
g
than that in crude oil by at least two orders of magnitude and, con-
sequently, the nickel emissions from engines fueled by such products are
very low. However, catalytic converters frequently include nickel.in
their casing materials or in the catalyst itself. Thus, the potential
for nickel emissions from catalyst equipped cars is greater than from
older cars.
In the mid 1960's several nickel-containing compounds were developed
by a petroleum company as deposit modifiers and preignition control
agents in gasoline engines. One of these compounds was used in gasoline
-2 -3
over a brief period at concentrations of 10 to 10 grams/gallon, but
its use was discontinued because of fear of nickel carbonyl emissions.
At present, there are no nickel compounds registered for use as gasoline
additives in the United States.
Nickel emissions from gas turbine engines have been estimated in
several recent studies. ' Development of automotive engines, tested
12
by Dow have given emission rates of 0.002 to 0.0034 grams/mile depending
on the cycle driven. Table 5.2 presents literature data for one gas
-------
Table 5.2.
DRAFT
DO NOT QUOTE OR CITE ,.....,
NICKEL EMISSIONS FROM SELECTED VEHICLES '''
Vehicle and equipment
Nickel emissions,
gram/mile
WR-26 Gas Turbine car
1974 Chevrolet, unleaded gas
1974 Chevrolet, Engelhard catalyst
1974 Chevrolet, AC catalyst
1974 Chevrolet, UOP catalyst
1974 Chevrolet, Mathey-Bishop catalyst
1974 Chevrolet, Gould reduction catalyst
Mercedes Diesel
1974 Pontiac, unleaded gas
1972 Pontiac, base metal catalyst
1971 Chevrolet, Engelhard catalyst
1971 Chevrolet, leaded gasoline
1972 Chevrolet, Gould reduction catalyst
0.003
0.00006
0.00023
0.00029
0.00024
0.00048
0.001
0.003
<0.0001
<0.001
0.003
0.0001
0.003
aTests performed according to the 1975 Federal Test Procedure.
Test performed according to the 1972 Federal Test Procedure (hot start).
-------
- \J i ' >••' '
turbine powered automobile, a Mercedes diesel, a non-catalyst equipped
car operated on lead-free and on leaded fuel, and several catalyst
equipped cars. In general, nickel emissions from non-catalyst equipped
cars are approximately 4X10" grams/mile over the Federal urban driving
cycle. Gas turbine emissions are about 100 times greater than baseline
while emissions from catalyst cars are characteristically in the 10"
grams/mile range. Nickel -bearing catalysts seem to have somewhat higher
emissions in a few tests.
Nickel levels in distillate products, such as gasoline or diesel
fuel, range from 0.001 to a maximum of about 0.1 ppm. At worst this
_c
nickel level would correspond to an emission rate of 3X10 grams/mile,
which is in fair agreement with the observed values. Most marketed
fuels have nickel levels much below the maximum value, however, and it
appears that .the observed nickel emissions are higher by a factor of ten
than can be accounted for by typical fuel nickel concentrations. It is
likely that engine wear products may account for this difference.
Table 5.3 presents nickel emission rates for aircraft turbine
engines determined in the EPA in-house programs. Although spallation
may occur in such engines, only traces of nickel were found in the
overall parti cul ate from these particular engines.
"Worst case" exposures for non-catalyst equipped car occupants or
nearby pedestrians to nickel oxide aerosol are, thus estimated at 0.1
- hour
yg/m for one hour peak exposures. Twenty-four/average exposures for
3
this "worst case" are estimated to be 0.015 pg/m . This case with
-------
00 NOT QUOTE OR CUE
liable 5.3. ELEMENTAL ANALYSIS OF PARTICULATE EMITTED
" FROM AIRCRAFT TURBINE ENGINES9
Concentration in particulate,
percent by weight
JT-8-D J-57
Substance engin engin
Nickel 0.19 0.3
Chromium - 1.4 Trace
Magnesium 0.008 0.3
Aluminum 0.62 0.5
Silicon 0.08 5.0
Sulfur 0.4 1.0
Engines run at 90 percent of rated oower. Participate concentration in
exhaust was: 11.7 mg/liter in the JT-8-D engin and 44.0 mg/liter in
the J-57 engin.
r o
-------
DO NOT QUOTE OR CITE
catalyst equipped cars would raise these exposures by about one order of
magnitude.
5.2 CONCENTRATIONS
5.2.1 Air.
Although there have been several studies concerned with nickel in
the air, only the National Air Surveillance Networks (NASN) data are
extensive enough in geographical and temporal dimensions to provide a
national index.
Table 5.4 contains annual average concentrations for those urban
NASN sites where all data were available for 1965 through 1969. Table
5.4 has been arranged in order of decreasing five-year average con-
centrations. Overall averages for these sites are to be found in the
last line of the table. The overall averages in this table were selected
for the sites having the most complete data. These averages are there-
fore not identical with the "best" overall averages for the nation for
the years shown. However, such "best" averages should not be very
different from the values given.
Table 5.5 presents data for the nonurban NASN sites, also selected
on the basis of data completeness, and arranged in order of decreasing
five-year averages.
Simple inspection of these tables will reveal the following:
o Urban concentrations are generally higher than nonurban
with the higher values being found in the industrialized
cities of the Northeast.
5-jo
-------
DRAFT
DO NOT OUCTf OR CITE
Table 5.4. ANNUAL AVERAGE NICKEL CONCENTRATIONS AT NASN URBAN SITES1"
(ng/m3)
Location
New Haven, CT
Philadelphia, PA
E. Chicago, IN
Reading, PA
Jersey City, NJ
Newark, NJ
Providence, RI
Portland, OR
Baltimore, MD
Wilmington, DE
Perth Amboy, NJ
Honolulu, HI
New Orleans, LA
Seattle, WA
Chicago, IL
Los Angeles, CA
Pittsburgh, PA
Louisville, KY
Oakland, CA
Youngstown, OH
Detroit, MI
Washington, DC
1965
85
122
154
61
69
73
41
59
33
38
59
39
16 .
39
37
18
23
40
23
16
18
28
1966
79
36
35
38
52
49
58
37
70
37
43
29
8
36
29
39
22
30
21
26
24
17
1967
92
62
35
38
75
77
37
41
42
40
68
26
12
27
31
23
27
29
31
19
26
28
1968
84
84
55
92
69
61
64
80
56
66
31
94
100
43
33
42
52
25
34
40
49
22
1969
139
96
103
122
64
55
112
70
75
93
44
44
73
49
50
30
42
29
34
45
25
42
5-year
average
96
80
76
70
66
63
62
57
55
55
49
46
42
39
36
34
33
31
29
29
28
27
5-II
-------
>n
Table 5.4 (Con't.)
DO ?
QUOTE OR
Location
Camden, NO
San Diego, CA
San Francisco, CA
Bayamon, PR
Hammond, IN
Columbus, OH
Warminster, PA
South Bend, IN
Indianapolis, IN
Norfolk, VA
Charleston, WV
Cleveland, OH
Glassboro, NO
Cincinnati, OH
Akron, OH
Chattanooga, TN
Concord, NH
Milwaukee, WI
Toledo, OH
Charlotte, NC
Kansas City, MO
Phoenix, AZ
1965
23
20
16
20
22
25
18
40
18
19
15
17
16
14
17
14
Oa
13
11
8
14
11
1966
44
23
28
13
14
16
21
17
18
10
12
10
11
12
11
11
11
9
8
9
0
13
1967
23
21
19
33
26
14
20
9
18
15
12
14
11
14
13
11
18
10
12
<0
8
11
1968
15
23
24
20
20
18
27
13
26
18
19
17
13
10
13
12
17
7
11
10
8
7
1969
23
40
28
22
29
30
18
20
22
27
21
20
25
19
12
15
16
11
8
11
9
A
5 -year
average
26
25
23
22
22
21
21
20
" 19
18
16
16
15
14
13
13
13
10
10
9
9
10
s-\:
-------
Averages
Table 5.4 (Con't.)
DON
DRAFT _
31 QUOTE OR CITE
Location
St. Paul, MN
Minneapolis, MN
Atlanta, GA
Des Moines, IA
Salt Lake City, UT
Nashville, TN
Albuquerque, NM
Boise City, ID
Helena, MT
Las Vegas, NV
Maricopa Co. , AZ
Memphis, TN
Oklahoma City, OK
Omaha, NE
San Antonio, TX
Tucson, AZ
Tulsa, OK
Wichita, KS
1965 1966
d) d)
d) d)
* v
8j.
(n
12
4* ())
(j)
(b d)
* *
d) d)
(j) $
1967 1968
10 12
4> 11
9 *
(b (b
((>
4> 4>
* 0,
4 4,
4, ^
4,
(b d)
(j, (j,
(j) (j)
d> (b
1969
12
10
9
7
*
4>
.*
4>
4)
*
4>
4>
4>
*•
5-year
average
9
8
7
7
7
7
(p
Cp
4)
4>
4>
4>
4>
4>
4>
4>
4>
*
25.5
20.2 21.6 28.5 32.3
25.6
a implies minimum detectable concentration or less = 6 ng/ni3 or less.
Averages computed using = 6ng/m3.
-------
Table 5.5.. ANNUAL AVERAGE NICKEL CONCENTRATIONS AT NASN NONURB0N SITES16
(nq/m3)
Location
Cape Hatteras, NC
Calvert Co., MD
Orange Co. , VT
Jefferson Co., NY
Clarion Co., PA
Coos Co. , NH
Parke Co., IN
Shenandoah Nat. Pk., VA
Blk. Hills Frst., SD
Cherokee Co. , OK
Curry Co. , OR
Glacier Nat. Pk., MT
Grand Canyon Pk. , AZ
Humboldt Co., CA
Matagorda Co. , TX
Thomas Co. , NE
White Pine Co., NV
Averages
1965
0*
0
4
3
0
0
0
0
0
0
0
3
0
0
0
0
0
0
1966
5
6
6
5
4
6
5
3
0
3
3
0
3
4
0
0
0
4
1967
0
13
9
4
5
0
3
0
0
0
0
0
0
0
0
0
0
3
1968
4
4
6
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1969
35
17
11
9
5
0
0
4
0
0
0
0
0
0
0
0
0
6
5-year
average
9
8
7
5
4
3
3
3
0
0
0
0
0
0
0
0
0
4
*0 implies minimum detectable concentration or less = 2 np/m3 or less.
Averages computed using 0 = 2.
-------
DRAFT
DO NOT QUOTE OR CITE
o Higher nonurban concentrations are found at the eastern
sites. These higher nonurban concentrations exceed some urban
/
values found in the western parts of the nation.
o There are no striking trends shown by the annual averages
in these tables.
Seasonal variation in concentration seems common although it is
not universal. In an attempt to assess this, the quarterly averages
for the cold months (quarters 1 and 4) have been compared to the quarterly
average concentrations for the warm months (quarters 2 and 3) by
forming a ratio. These ratios should have values consistently different
from one if a seasonal affect is observed. Data of this kind are
presented in Table 5.6 for selected urban sites and in Table 5.7 for
some nonurban. sites. Only sites with the higher quarterly averages
were used in this exercise. This was done because as concentrations
approach the minimum detectable the numbers become small and the
ratio becomes extremely sensitive to normal analytical errors. Inter-
pretation then becomes difficult. Such difficulty is apparent in
Table 5.7 where all available concentrations were small and some ratios
are, in fact, indeterminate because the actual concentrations were
smaller than could be measured.
With these limitations in mind, the data in Table 5.7 suggest the presence
of a seasonal nonurban variation with the higher nickel concentrations
occurring in the cold months. Note, however, that all of the sites in
this table are in the eastern part of the country. Nearly all values
from the nonurban Midwest and West are so low that the ratios are
indeterminate. No conclusions may be drawn about those sites.
The first ten entries in Table 5.6 are the ten urban sites with
-------
DC NOT OUOTE OR CITF
Table 5.6. SEASONAL VARIATION IN NICKEL v
CONCENTRATIONS AT SOME NASN SITES?'16
New Haven, CT
Philadelphia, PA
E. Chicago, IN
Reading, PA
Jersey City, NJ
Newark, NJ
Providence, RI
Portland, OR
Baltimore, MD
Wilmington, DE
Honolulu, HI
New Orleans, LA
Houston, TX
1965
1.6
3.8
7.8
1.6
2.2
1.6
2.2
1.9
1.7
1.4
1.0
2.5
1.2
1966
1.3
1.7
1.2
1.7
1.9
1.3
2.3
1.5
2.3
1.9
1.9
2.1
1.1
1967
2.7
1.3
1.5
3.2
6.1
1.2
1.4
0.5
1.6
1.6
1.3
J)
™
1969
3.3
1.3
\
8.7
6.4
1.3
1.6
5.4
1.6,
1.6
2.6
1.1
2.8
0.98
aRatio of quarterly concentration for the colder six months (quarters 1
and 4) compared to warmer six months (quarters 2 and 3).
Data not available.
-------
DRAFT
Table 5.7. SEASONAL VARIATION IN NICKEL . rr> MAT HliOTF OR
CONCENTRATIONS AT SOME NASN NONURBAN SITES3 uiu
Cape Hatteras, NC
Calvert Co., MD
Orange Co., VT
Jefferson Co., NY
Clarion Co. , PA
1965
b
P
P
P
1.8
P
1966
3.8
1.6
1.2
0.9
1.2
1967
1.8
1.2
1.6
1.0
1.3
1969
0.5
2.6
1.6
1.6
2.8
aRatio of quarterly concentrations for the colder six months (quarters 1
and 4) compared to warmer six months (quarters 2 and 3).
Bp implies an indefinite ratio caused by a value of 0 for the denominator "
or numerator and denominator. 0 implies the minimum detectable concen- -
tration or less.
r.,7
-------
l/IVrtl I
DO MOT QUOTE OR CITE
the highest 5-year average concentrations. Those ratios are (with
one exception) greater than one which also indicates generally higher
nickel concentrations in the cold months than in the warm months.
All of these sites except one are in the industrialized Northeast.
This seasonal variation is usually attributed to the increased
burning of fossil fuels during the cold weather. Such sweeping,
one parameter explanations may be inadequate and merely g!ib:
if applied indiscriminately. For example, the last three
entries of Table 5.6 have been chosen for site locations in warm
climates. If the usual explanation for seasonal variation is valid
it would probably be absent at such sites. In the case of Houston,
that consideration seems correct since all ratios are near one. For
New Orleans, geographically near Houston, seasonal variation is
marked and sustained. For Honolulu the situation seems mixed.
In 1970 the nickel content of various particle size fractions was
19
measured at six urban NASN sites. Less than half (31 to 49
percent;Of the mass of nickel-associated aerosol was found to be in
particles with mass median diameters of less than 1 micrometer.
5.2.2 Water
The amount of nickel in seawater ranges from 0.1 to 0.5 yg/liter.
Nickel rarely occurs in ground water; when it does occur, it is
usually in the insoluble minerals of the hydrolyi-ates. Thus, nickel
in surface water is likely to be i:'i small amounts unless it is from
industrial waste.
-------
o ftr<"iT /""'Tr'" r"*. "ITP
rtJ! Q-juk OK JTE
Nickel was identified in U. S. waters with a frequency of 16 percent.
The Missouri and Western Gulf basins had the lowest frequency of
were
nickel detection, and/among the lowest mean concentration levels (Table 5.8.
The highest mean concentrations was 130 yg/mer
20
in the Cuyahoga River at Cleveland, Ohio.
5.2.3 Soils
Soils are formed from rocks, therefore, the composition of a soil
depends upon the composition of the parent rock from which it originated.
Variations in the nickel concentration of the parent rock means that
variations in soil will occur from region to region. Continental
glaciation also had an effect upon the soil levels of nickel and
u • 21
chromium.
22
Mitchell divided soils into two groups: those originating
from sandstones, limestones or acid igneous rocks and containing less
than 50yg/g of nickel; and those derived from clayey sediments or
basic igneous rocks and containing from 5 to 500 pg/g of nickel.
23
Bowen lists the nickel content of igneous rocks as 75 yg/g» shales
68yg/g, limestones 20yg/g with soils averaging 40u9/9 unless they are
derived from serpentine soils. Serpentine soils commonly contain
a high percentage of nickel, iron, and chromium. Nickel is concentrated
with iron in laterite, a hard ,red soil which is found in tropico and is
low in silica and high in iron and aluminum. Nickel concentrations
in serpentine soils ranges from 5 to 6000 yg/g with an average of 3000
yg/g.21
y- /
-------
DRAFT
nn P'^T c"''''. 'rr f"1 riTF
UU \.'^ 1 V^,; O iL Uik UllL
lable 5.8. NICKEL IN WATER FROM MAJOR RIVER BASINS OF THE UNITED STATES20
Meiin nickel concentration, Frequency
Hi vor hasjn |ij4/liter of detection, % .
Nort.hea.-it 0 22.0
I
! Horl.h Atlantic 0 ?0.1
«ui,c;i!} |
i
i TcnniiSJino Hivrr ' )|
I
Ohio Hi ver 31
l.:ik<- Krio rjh
Mr;-, l.crii Cifnut .Liakcn
Hi:;:;onri Hivor
iMiiil.hwi.-r, l,-l,ower MiQdirtsJppj.
Color.-uJo Hlver
y--:; l.crn Gulf
I'.'irifir Northweut
C;il i Cor 11 in
i;rc::i.l. M;inin .
Aln:;k;i
.1.0
•j
17
12
3
10
10
'•
5
9-1
2.0
9 . 7
H.O
2.1
10 . 5
13.0
15.0
11.1
-------
DRAFT
• •-- r.n rirr
','!; U j t
23
Vanselow cites the studies of a number of workers from around
the world. Concentrations of nickel in the soils listed by these
workers vary from 1 to 730yg/g for non-serpentine soils. Levels in
soils in the U. S. were listed as ranging from 1 to 100
24
Klein studied surface soils from industrial, agricultural>
and residential areas. He analyzed the soils to determine the presence of calci
cadmium, cobalt, chromium, copper, iron, nickel, lead,silver and zinc. An
of
analysis/264 soil samples from a 300 sq. mile area indicated that metal concen-
trations were higher in industrial soils than in residential or urban
areas. The enrichment for nickel was approximately 1.4 times that found
in the residential zones. Airport soils were significantly enriched.
Agricultural soils tended to run a little higher than the concentrations
in residential zones (Table 5.9).
The addition of sewage sludge or phosphate fertilizers can also
25
raise the concentrations of nickel in soil. Studies by Yost et al. showed thai
the amount of nickel in fertilizers ranged from 3.0 - 38.0 yg/g. The nickel
content of sludge varied from <32 to 2900 yg/g dry weiaht.
The concentrations of nickel in the soil along highways may be
26 26
increased by fallout from automobiles. Lagerwerff and Specht
have shown that the concentrations of nickel are higher along highly
traveled throughways and decrease the farther one gets from the
highways. The range was from 7400 yg/g near the highway to2220 yg/g
32 meters away.
-------
Table
Residential
N - 70
Agricultural
N ='91
Industrial
N = 86
Airport
N - 7
5.9
median
mean
stddev
median .
mean
sld dev
median
mean
std dev
median
mean
stddev
Industrial/residential
Airport/residential
[
,' ' J i '; H,
METAL CONCENTRATIONS
Ag
0
0.13
0.19
0
0.19
0.25
0.4
0.37
0.33
0.4
0.29
0.30
2.85
2.24
Ci
1,000
2,300
2,600
800
1,400
1,900
1,900
3,200
3,000
3,700
4,100
3/800
1.39
1.78
Cd
0.4
0.41
0.44
0.4
0.57
0.52
•*0.7
0.66
0.54
0.7
0.77
0.56
1,61
1.88
Co
2
2.3
1.5
2.5
2.7
1.5
2
2.8 •:•
1.8
8
7.9
2.7
1.22
3.43
Cr
1.6
3.2
3.3
3.9
4.6
3.6
6.0
8.5
9.0
22
17.6
8.9
2.66
5.50
•>,--• ••••: '
..' s \, ' '"
_.t i u.
-------
DRAFT
5.2.4 Punts DO NOT QUOTE OR CITE
23
The nickel content of plants is usually less than lyg/g. *
Only plants growing on serpentine soils have higher levels. Table
5.10 shows the concentrations of nickel found in a wide variety
of plants. It may be noted that many of the plants listed in the
table are used by man as food.
Plants exist which are capable of concentrating nickel in their
tissues.27 Alyssum bertolonii, which grows in Italy and the Western
Balkans usually contains up to 5-10 percent (ash weight) of nickel.
Pimilea suteri, from New Zealand, accumulates not only nickel (2.5
percent ash weight} but alsd? chromium. Species of Hybanthus, par-
ticularly H_. floribundus. from Australia, have been shown to accumulate
nickel and cobalt. Growing in soils containing in excess of 400 ya/g,
these plants were shown to be capable of concentrating nickel at levels
up to 3,665ug/g in leaf tissue. The maximum nickel concentration in
leaf tissue was 26 percent (ash weight).
Knobcone pine.? Pinus attenuate, and tanoak, .Lithocarpus densiflora.
growing on serpentine soils near Curry, Oregon, were reported to have
21
a maximum nickel content of 300 P9/Q and 630 pg/g respectively.
5.2.5 Microorganisms
Nickel is not a constituent of microorganisms as far as is
presently known, but is toxic to a majority of them.
Millerite (NiS) is oxidized by the Thiobacillus - Ferrobacillus
group. In general, the bacterial oxidation of this mineral results
the formation of nickel sulfate and hydrogen sulfide. The process
occurs only under an acid pH.
28,2S
5"- it3
-------
Table 5.10. TISSUE ANALYSIS VALUES USEFUL IN INDICATING NICKEL STATUS 23
.
r,
Plant
Alfalfa
(A/erftcoyo tativa)
LjJ "' '
— T, AlyMura
OC: Apricot
r~> (frunm arrmeniaee)
;_i_l Barley
1 r/fpr^fum Before)
T^ Bean
;-3 (Phattolu* spp.)
Bog asphodel
I ' (WarlAecium spp:)
f*"""*
~»» Buckwheat
^^ (faaonnrmn spp.)
~?" Bulrush
C-J g (Scirpui cauptloois)
Cabbage
(Broagicp okrocgfl cepttoto)
Carrot
(DoiKut coTolo tati»*)
Cherry
(Prunui ceratvl)
Citrus fruite
(CifriMspp.)
Clover, bur
(UeJicago kifgUf)
Clover, red
f Tri folium protenatl
Coffee
Type of
culture
Field
Field
Field
Field
Field
Field
Field
Field
Field
Field
Field
Field
Field
Greenhouse
Greenhouse
Field
Pota
Field
Field
Field
Field
Tissue
sampled
Tope
Leaves
Seeds
Fruit
Leaves
Seeds
Leavea and
stems
Seeds
Leaves and
stems
Tope
Roots
Leaves
Fruit
Leavea
Leaves
Leaves
Leaves
Leaves
Tope
Tope
Bean*
Age, stage, condition
or date of sample
Mature
Mature
Mature
Mature
May, 1955
Mature
Mature
Mature
Mature
Edible
Mature
Mature
Mature
Young
Mature
Mature
Mature
Mature
Mature
Mature
Mature
Range in dry matter (ppm.)
Showing defi-
ciency symptoms
Low
range
Intermediate
range
1.00-4.00 !
0.65
0.59
0 40-5.30
1.34
0.30-3.00
3.30
0.30
1.80
0.50
0.40
1.00
2.00-1.00
0.70-1.80
0.40-1.00
1.00-2.00
1.90
0.40
High
range
4,000.00
2,500.00
4.00-4.00
.. .
...
Showing tozie-
ity symptom* '
55.00
140.00
-------
Table 5.10 (continued).
TISSUE ANALYSIS VALUES USEhUL IN 1NU1CAI 1Mb
(yg/g)
O
o
Plant
!
Corn
IZtt magi)
Cress, water
luutwtium-aawiticwn)
Fi«
(fievt conca.}
GRASSES
Sweet vernal grass
Various grass spp.
Heather and Heath
(Cgfluna vtdg art*)
fjgriea eingreo)
(Erica tefrnZirt
• Mushroom
i (QantAarelZtu ct'6ort'u<)
Oats*
Onion
(Xflium eepo)
Pea
(Pj»um »oliimm)
Pear
(£ltrjl4 Cffmmuni*)
Potato
'
Rice
(Qrysa^jiafr'po)
(Corel spp.)
Soybean
«jlncini toja)
1
[Type of
culture
Field
Field
Field
Field
Field
Field
Field
Field
Field
Field
Field
Field
Field
Field
Field
Pots
Field
Field
Field
Field
Field
Field
Field
Field
Tissue
sampled
Grain
Tope
Leaves
Fruit
Tops
Tops
Tops
Tops
Tops
Tops
Tops
Buttons
Grain
Leaves
Leaves
Tops
Bulbs
Seeds
Fruit
Tubers
Tubers
Grain
Tops
Seeds
Age, stage, con-
dition or date
of sample
Mature
Mature
Mature
Mature
Mature
Mature
Mature
Mature
Mature
Mature
Mature
Edible
Mature
June
Mature
Mature
Mature
Mature
Mature
Mature
Mature
Polished
Mature
Mature
Rar
Showing
defi-
ciency
symptoms
ige in dr
Low
range
~y mattet
Inter-
mediate
range
0.14
0.50
0.13
1.20
0.70-1.70
0.20-0.80
...
0.60-3.00
0 90-2 60
1.50-1.70
1.10-1. SO
3.50
0.45
18.0fr-51.00
7.00
0.18
2.00
1.30
0.25
0.08-fl.37
0.02
0 20-3.20
3 90
" (ppm)
High
range
9.00-58.00
134.00
3200
84.00-340.00
Showing
toxicity
symptoms
rx
-------
Table 5.10 (continued).
TISSUE ANALYSIS VALUES USEFUL IN INDICATING NICKEL STATUS
( yg/g)
23
PUnt
Spinach
(Sptnoria oieraeca)
Squash
(Cttewbila ipp.)
Tea
(Camellia rincnlil)
Timothy
(PUeum prabnj*)
Tomato
(Lycoperiicon eKufen(um)
Walnut
(•/Ufianj reffia)
Wheat
(Triticum spp.)
Type of
culture
Field
Field
Field
Field
Field
Field
Field
Field
Field
Field
Field
Tisaue
•ampled
Topi
Fruit
Leaves
Topi
Fruit
Fruit
Leave*
Meats
Grain
Grain
Grain
Age, itage. condition
or date of sample
Mature
Mature
Mature
Mature
Mature
Mature
Mature
Mature
Mature
Mature
Mature
Ilange in dry matter (ppm.1
Showing defi-
ciency qrmptomi
Low
range
Intermediate
range
2.40
4.80
300-600
0 48
0 15
0.01
0.90-5.00
0.80
0.31
4.00
High
range
3500
16.00
Showing toxic-
ity symptoms
Reference
Bertrand and Mokragnati (19:lOc)
Bcristein (1945)
Layeock (1954)
Mitchell (1945)
Bertrand and Mokragnati (1930c)
Bertrand and Mokragnati (1930a)
Vanselow (1945)
Bertrand and Mokragnati (1930e)
Bertrand and Mokragnati (193%)
Sullivan (J933)
Vergnano (1959)
-43
Ci
-------
DRAFT
526^ KOT QUOTE OS CITE
Among the first transition series of elements, chromium, manganese,
iron, cobalt, copper,and zinc have been shown to be essential to the
health and life of animals. It is highly probable that nickel,
located in the midst of that series, is also an essential element in
animals.
5.2.6.1 Sea Animals—The average concentration of nickel in sea water
is about O-1 to 0.5 pg/liter. Nickel is concentrated in a
variety of fish and crustaceans as illustrated in Table 5.11. The
concentrations represent enrichment of up to several orders of
magnitude over sea water levels.
5.2.6.2 Land Animals--Analyses for the presence of nickel, primarily in
serum, have been made in a variety of animals. Table 5.12 summarizes
serum nickel levels in healthy adults of a variety of species. Measurements
are made by atomic absorption spectrometry, using the standard pyrrolidone
dithiocarbomate complexation, methylisobutylketone extraction procedure.
Conclusions about these values reached by Sunderman et al. indicate
no significant difference between sexes for any of these species.
Dietary studies on cattle receiving up to 250yg/g nickel for an 8-week
period showed that no increase of nickel was apparent in liver or
kidney, although there was some increase in the lung. Another feeding
supplement study, with cows receiving up to 1750yg/g nickel salts,
resulted in no increase in the nickel levels of the milk produced.
-------
Table 5.11. NICKEL CONCENTRATIONS IN FISH AND CRUSTACEANS
1
Seafood
Nickel concentration,ug/g (fresh wt)
Oysters, fresh
Mollusks (Puget Sound)
Clams, Fresh
Shellfish (Japanese)
Scallops, fresh-frozen
Lobster, claw meat
Shrimp, fresh-frozen
Crabmeat, canned
Anchovies, canned
Sardines, canned
Haddock, frozen
Swordfish, frozen
Salmon flesh
ui'cSScvj-i i3n Sump i c3 I
whitefish, Moose Lake
northern pike,-Moose Lake
whitefish, Lake Ontario
northern pike, Lac St. Pierre
northern pike, Lake Erie
smelt, Lake Erie
yellow perch, Lake Erie
1.50
0.74
0.58
0.14
0.04
0.66
0.03
0.03
0.72
0.21
0.05
0.02
1.70
0.2
0.2
0.2
0.2
0.2
0.2
0.2
-------
DO MOT QUOTE OR Cut
Table 5.12. NICKEL IN THE SERUM OF HEALTHY ADULT ANIMALS OF SEVERAL SPECIES31
Species, and number ^f animals
tested
Domestic horses (4)
Man (47)
Jersey cattle (4)
Beagle dogs (4)
Fischer rats (11)
British goats (3)
New Hampshire chickens (4)
Domestic cats (3)
Guinea pigs (3)
Syrian hamsters (3)
Yorkshire pigs (7)
New Zealand- rabbits (24)
Nickel Cone.
(pg/D
Mean
2.0
2.6
2.6
2.7
2.7
3.5
3.6
3.7
4;1
5.0
5.3
9.3
1.3
1.1
1.7
1.8
0.9
2.7
3.3
1.5
2.4
4.2
3.5
6.5
Range
- 2.5
- 4.6
- 4.4
- 4.2
- 4.1
- 4.4
- 3.8
- 6.4
- 7.1
- 5.6
- 8.3
- 14.0
-------
DO NOTUQUOTE OR CITE
5.2.6.3 Humans--The normal human has within his body approximately 10 mg
of nickel; however, wide individual variations exist. Extensive studies
have been conducted to determine the distribution of nickel in tissues
of the human body, liver and excretion. Much of the work on the tissue
oo "54
distribution has been done by Tipton and her colleagues. They
performed autopsies on: 1) apparently healthy Americans who died
suddenly, with no apparent disease at the time of death, and, 2) on
foreign adults from the eastern hemisphere, many of whom had chronic
illnesses at the time of death. The nickel content of 29 tissues from
150 adults was determined by emission spectrography. Nickel was observed
in only about one third of all the samples analyzed, although it was
observed in every tissue, the greatest frequency and the highest con-
centration occurred in skin.
The body does not readily retain nickel; retention seems to be
around only 3.6 percent. Studies of lungs of selected groups, ranging
from victims of nickel carbonyl poisoning to normal subjects, show a
gradient in nickel levels. (Table 5.13). Miners showed a small but
significant increase in nickel content over the general population,while
victims of nickel carbonyl poisoning had very high nickel levels.
Nickel has been measured in hair, excreta, and blood. Hair measurements
have produced varied results, presumably because of differences in
sampling the hair, and in the work techniques used before the analysis.
•jr
Nechay and Sunderman reported average nickel levels of 0.22 yg/g (range,
0.13-0.51; S.D.+0.08) in hair segments taken not more than 5 cm from the
scalp, with no significant difference between men and women.
-------
uiw i „ rlTC
DO NOT QUOTE OR CITE
Table 5.13. NICKEL IN LUNG TISSUE OF ONTARIO SUBJECTS
1
Nickel content of lung, yg/100g
Subject
Normal lungs
Male
Male
Male
Male
Female
Female
Female
Ore miners
Male
Male
Male
Male
Male
Male
Victims of Ni(CO),
Male .
Male
Male
Male
Age
50
52
71
75
23
35
48
-(27)a
--(19)
-(20)
•--(21)
-(17)
-(39)
poisoning:
D
~" ™ L
b
™ ™ i
b
™ ™ i
b
Wet tissue
0.018
0.021
0.021
0.017
0.009
0.010
0.014
7.2
9.7
10.9
16.1
Dry tissue
0.091
0.119
0.175
0.116
0.060
0.102
0.083
o:se
0.25
0.22
0.49
1.36
0.48
39
63
67
97
Ash
4.0
2.0
5.0
4.8
4.0
5.0
5.0
8
6
7
12
13
10
975
1,450
1,550
1,950
JAge not available, years as miners given in parentheses.
DAge not available, years of work experience given as 10 to 25 years,
5-3!
-------
SO ROT QUOTE OR CITE
36
Schroeder and Nason reported nickel levels of 0.97 yg/g [S.E.M. =
+_ .15] for men's hair and 3.98 yg/g [S.E.M. = +_ 1.06] for women
(significant differences at p <0.0001).
Most orally ingested nickel is excreted in the feces. In a limited
study, Horak3 feund that nickel levels in the feces of healthy
subjects averaged 3.3 +_ 0.8 yg/g net weight. Average levels of
nickel in urine have been measured in many laboratories (Table 5.14).
Variability among them is great, with means ranging from 0.20 vg/100 ml
to 9.3 yg/100 ml. Sweat appears to have significantly higher levels
of nickel than urine, with 52 +_ 36 yg/liter in men, and 13_1 +_ yg/liter
38
for women, and has been identified as an important route for the
excretion of absorbed nickel from the body.
Investigation in Sunderman's laboratory has demonstrated that nickel
exists in three forms in human blood: (l).as ultrafilterable nickel,
bound up in some as yet unidentified complex form, (2) as albumin
as
bond nickel, and'(3X a nickel metalloprotein that has been named "nickelplasma".
Many studies of nickel levels in whole blood, serum and plasma have been
made. Variability in the reported results is great, but as sensitive
atomic absorption methods have developed, reproducibility has improved.
39 oe
A study measuring the serum nickel
levels among groups of adult residents of Hartford, Connecticut,
a city with relatively low environmental nickel concentrations, and
comparing them with levels from a group of adult residents of Sudbur.y,
Ontario, Canada, the site of the largest open-pit nickel mine in North
America, indicated that measurements of nickel in serum could be used
to reflect environmental exposure to nickel. In the Hartford population,
serum nickel concentrations averaged 2.6 +_ 1.0 yg/liter, while the Sudbury
-------
DO NOT QUOTE OR
Table 5.14. CONCENTRATIONS UK NICKEL IN HUMAN URINE
Method
Spectrophotoinetry
Spectrophotometry
Emission spectrography
Spectrophotometry
Emission spectrography
Atomic absorption
Atomic absorption
Atomic absorption
Spectrophotometry
Atomic absorption
Area
England
Pennsylvania
Missouri
Wales
b
Pennsylvania
Connecticut
Germany
Yugoslavia
Connecticut
No.
subjects
12
69
24
?
154
17
26
15
10
20
Nickel conce
g/ioo
Mean
2.9
1.1
2.0
4.0 ±0.2
1.0
1.8 (19:8)
0.23 (2.4)
9.3
2.7
0.20 (2.5)
ntrations
ml*
Range
0.0 -
. 0.0 -
1.0 -
--
0.1 -
0.4 -
0.10 -
(1.0-5
(5.7 -
1.4 -
0.07 -
(0.05
»
5.5
3.0
7.0
2.5
3.1
0.'
.6)
12
6.3
0.'
- 6
Canada
19
0.72
a Numbers in parentheses are concentrations in micrograms per day.
b Industrial workers from Ohio, New York, Florida, Colorado, and Oregon.
0 Sudbury, Ontario.
0.21 -•!
> .3 3
-------
\ DO NOT QUOTE OR CITE
population serum nickel concentrations averaged 4.6 +_ 1.4 yg/titer.
The differences were significant at p <.001. One caveat appeared in
connection with the study: there was no evidence that the environmental
exposure to nickel in Sudbury, Ontario was associated with adverse effects
in man or animals.
-------
DRAFT
DO NOT QUOTE OR CITE
rO TRANSFORMATION AND TRANSPORT MECHANISMS
5.3.1 Natural Mechanisms
In general, the atmospheric loading of participates is determined
by the rate of input of primary participate and gases, the rate of
transformation of pollutant gases into particles, the transport of
primary and secondary pollutants through the atmosphere and the
removal processes. Nickel-containing particulates will enter the
atmosphere as primary particulate emission. Details concerning the trans-
formation and transport of nickel-containing particles are not known.
This is unfortunate because in order to relate the quality of the environ-
ment to the sources of pollution and in order to predict the control
needed under present and future conditions, an accurate assessment
of the inpact of these processes upon the atmospheric loading is essential.
At the present time we cannot even make an estimate of the residence
time of nickel in the atmosphere nor do we know the ultimate fate of
nickel.
Transformation and transport processes can be divided according to
is,
the type of mechanism involved,that / chemical mechanisms, physical
and dynamic mechanisms, and biological mechanisms.
• - ,-•-• .1.-. ...... .- . _ .
Figure 5.1
depicts the transformation and transport of nickel inthe ecological
system. The discussion in the following
paragraphs shows that much additional study needs to be undertaken
in order to assess the importance of the various mechanisms depicted
in Figure5.1.
5-35
-------
DRAFT
J» WOT QUOTE-OR CITE
F1 g.. ,,5; 1 • Tto cydtaf of mkroekmenu.
-------
5.3.1.1 Chemical Mechanisms—The forms of nickel in air and their
reactions have not been extensively studied. It would be expected that
nickel would be present predominantly in particles. However, owing
to the industrial importance and widespread usage of nickel carbonyl,
the possibility of nickel enetering the atmosphere as nickel carbonyl
should not be overlooked. For example, the regeneration of fluid catalysts
used in petroleum refining involves burning coke and carbon
off zeolite catalysts. Nickel carbonyl is formed in the process.
Although this compound is recognized as a hazard in industrial hygiene
there seems to be little information available as to the amount of
nickel carbonyl which escapes to the atmosphere.
Little, if anything, is known jjbout chemical transformations of
metallic elements in the atmosphere. There is a need to know whether
nickel is present as a nitrate, sulfate, or some other compound, and whether
these compounds undergo further reaction, either catalytically or directly.
Particles in the atmosphere are believed to participate in some of the
reactions associated with photochemical smog. Laboratory results have
suggested that the oxidation of gases, such as sulfur dioxide, is accelerated when
particles are present. However, the involvement of nickel-containing
particles in such heterogeneous reactions has not been assessed.
-------
tmar i
DO MOT QUOTE OR CITE
1.1
I
The soil chemistry ; . ;
of nickel is a crucial factor in physical and biological transport
!~- but there is no chemical transport per se. Soil pH is highly significant.
* *i •
"7" In acid soils, nickel compounds are more soluble and, consequently,
o 41-44 '
more available for transport in soil solution or uptake by plants.
Liming soil to increase the pH decreases the solubility and is an established
41 44 45 ...
treatment for plant toxicity due to excess nickel. ' '* 'AS the pH moves
toward neutrality, nickel probably precipitates with'; the calcium supplied
by lime or limestone and there is evidence to suggest that in slightly
41.44.4C
acid to neutral soils nickel will precipitate with available phosphorous.
Formation of complexes and chelates between nicke.l and the degradation
products of soil organic matter may increase, depending on pH
solubility and mobility
43,44,47,48
of nickel in soils. Adsorption at exchange sites on soil clay minerals
and soil organic matter will remove cationic forms of nickel from
41,43,44
solution. This mechanism will be more significant in soils with a
high organic content or a high content of silicate clay minerals
and particularly for those soils with a clay fraction dominated
by montmorillonite or illite. In neutral and alkaline soils, only
small amounts of nickel will be adsorbed on exchange sites because
precipitation reactions will lower the concentration in solution below
4 3
that of other exchangeable cations.
-------
DRAFT
DO NOT QUOTE OR CITE
5.3.1.2 Physical and Dynamic Mechanisms—Those physical and dynamic
processes which affect the physical properties of particles in the
.. . 49
atmosphere are:
o Sain or loss of particles entering an air mass by diffusion
or convection from neighboring air masses.
o Net change in particle concentration by thermal (Brownian)
coagulation.
-------
DO NOT QUOTE OR CITE
o Net change in particle concentration by scavenging of smaller
particles by larger ones during their fall.
o Net change of particle concentrations by collisions between
particle^ resulting from turbulent velocity gradients.
o Loss of particles by gravitational sedimentation.
o Loss of particles by impaction on obstacles at the earth's
surface.
o Loss of particles by diffusional diposition on surfaces
o t Loss of particles by washout and rainout
The degree to which these processes are important is a function of
50
particle size and altitude of the air mass. Little information is
available on the detailed mechanisms by which airborne nickel-containing
particles participate in these processes.
The transport of particles in the atmosphere is controlled
primarily by wind. Brownian motion diffusion will be insignificant
when compared to the convective diffusion produced by turbulent air
motion.
Large sized nickel-containing particles would be expected to fallout
in the near vicinity of their source by gravitational sedimentation.
Particles can also be deposited on surfaces by diffusional deposition
and by impaction on obstacles at the earth's surface. Precipitational
removal processes such as rain-out and wash-out are also important
factors.
Particles deposited on ground surfaces may be further transported
by ground water, probably eventually ending up in the oceans. No estimate
is available on the amount of nickel added to the ocean each year.
•5" 4O
-------
DRAFT
DO NOT QUOTE OR CITE
Most of the nickel in surface and ground waters is believed to be due to
industrial Pollution. .
Both the chemical and physical processes occurring within an air
mass will affect the size distribution of the aerosol. Nucleation,
condensation, coagulation, and gas-particle reactions all play a role
in determining the size-composition distribution.
Condensation upon existing nuclei and the generation of new particles
by nucleation and condensation processes are other important mechanisms
affecting the size distribution. Specifics of the agglomeration of
particles are unclear and much work is needed in this area.
t
Important physical transport mechanisms in soils are the
the
downward movement in solution and/erosion of solid material from the
soil surface. Quantitative data on movement down through different
types of soil and on the extent of erosion transport are not available ,
but some qualitative estimates can be made.
Other things being equal, downward transport will be more rapid
in coarse textured soils than in fine textured soils because of the
larger pores and faster movement of the soil water. Similarly,
transport through the soil will be faster in higher rainfall areas
•44
because of the potential for more water entering the soil. Transport
in solution will be affected not only by the amount and rate of flow
of soil water but also by the previously discussed chemical mechanisms
which control the concentration of nickel in the soil solution.
For soils in which added nickel remains near the surface because
chemical mechanisms limit the concentration in soil solution, there
is the possibility that soil particles with adsorbed nickel or
-------
vi u i
DO NOT QUOTE OR CITE
precipitates of nickel will be eroded from the surface by irrigation
44 *
and/or rainfall and carried into surface waters. This would be a
particularly significant addition and should be considered when designing
disposal sites for sewage or industrial sludges where the soil has been
selected or treated to maximize heavy metal retention in the surface
layers such as S01'is wnich nave naturally high pH and calcium content
or soils which have been treated to produce these conditions.
5.3.1.3 Biological Mechanisms
The principal biological mechanism for transport of nickel is
plant uptake. Although nickel is not an essential plant nutrient it
is absorbed by plants from the soil solution. The extent of such
uptake is influenced by the concentration in the soil solution,
soil temperature, pH, nutritional status of the plant, and by the
formation of organic complexes and chelates which increase the
solubility and mobility of nickel in soil but reduce its availability
41-48,51
for uptake by plants. In some cases, plant toxicity
due to excess nickel in solution has been alleviated by application
of sewage sludge which is of high organic content and contains significant
35
amounts of nickel. The organic matter forms complexes and chelates
making nickel unavailable to plants. If the applications were not continued, the
; 42.
-------
DRAFT
DO ROT QUOTE OR CITE
nickel-organic compounds eventually . breakdown by microbial
action and the nickel again becomes available for plant uptake or
participation in soil chemical processes. There are differences in
uptake due to the type of plant, and within the same plant there
will be differences in nickel concentration between leaves, stems,
41
fruit, and roots.
After uptake by a plant, ' . nickel may be distributed
to humans and animals as food or returned to the soil in unused
plant parts. In soils where nickel is relatively immobile, plants
can extract nickel from deeper soil horizons and concentrated
the nickel in the surface layer of the soil by the decay of the
plant parts. Emission transport can carry this n1fckel to surface waters.
Microbiological transformations of organic matter in the soil are
important in binding nickel to and releasing it from organic
complexes and chelates.
Earthworms living f* soil w'ith a high nickel content have been
cp
shown to contain high concentrations of nickel
Airborne nickel may be deposited on vegetation and may enter the
plants through the leaves, unless carefully washed, the nickel dust
adhering to the vegetation may enter the digestive tract of organisms
eating it. If the vegetation is not eaten, the nickel returns to
the soil during the decay process .
-------
UiUtfl
DO NOT QUOTE OR CITE
Mosses and lichens tend to accumulate heavy metals largely through
deposition, Moss tissues have a great capacity for sorbing heavy
53 54
metal s, .-* Negatively charged organic .groups in, moss., tissues sorb ;
the cations of the heavy metals selectively from dilute solutions,
Nickel, along with copper, lead, chromium, cobalt, cadmium, zinc
and manganese, is sorbed by the moss tissues and eventually incorporated
into the moss carpet. The capacity for capturing heavy metals is not
55
unique to mosses and lichens. An increase in the above listed heavy
metals is seen in most plant material as it begins to
decompose. Dead organic matter prior to decomposition is usually much
richer in heavy metals than the living plant material of the same type.
This increase in heavy metal content of litter is due chiefly to its
55
ability to sorb the metal ions.
-------
. .
*-* V I ', :„•• J !?>''•. . ' :
'*. ' '" ' "~ "•• • " >.•«»*,
Very little is known about the chemistry of nickel and its compounds
in seawater, The chemistry of nickel and its compounds in solution^
especially in the presence of carbonate and stilfide ions,is largely
2+x
that of bivalent nickel (N«'• Calculated according to Liebig's
Law of the Minimum, which states that the growth of a plant is dependent on the
the
amount of nutrient which is present in/least quantity, the concentration
42
factor of nickel, is among the lowest in the transition metal groups.
Goldberg et al?7 reportthe concentration of divalent nickel (Ni+2)
in seawater as 7 yg/liter and in streams as 0.3 yg/liter.
Residence time in the oceans is listed as being 90,000 year's.
Ranges of element concentrations in marine organisms at various
trophic levels are listed in Table ^-15.
-------
Table 5.15. RANGES OF NICKEL CONCENTRATIONaFACTORS IN MARINE ORGANISMS AT VARIOUS TROPHIC LEVELS58
ATgae
Sessile
50 to
1,000
Plankton
Phytoplankton
and Sargassum)
25 to 300
Grazes
Plankton
(Copepods,
Pteropods, Salps,
Doliolid)
2 to 1,000
Shellfish
4, 000 .to 40,0
Predators
Plankton
[Euphausiids,Planktonic
Amphi pods, Shrimp
(Acanthephyra,
Paleomonetes)]
00 17-190
Fish
—
Squid
30-80
Concentration in whole, fresh organisms versus concentrations in seawater.
•=*•
(J\
-------
DRAFT
5.3.2 Man-made DO NOT QUOTE OR CITE
The disposal of municipal solid waste presents one mechanism for
the reentry of nickel into the environment, the disposal routes normally
encountered are incineration and landfill ing. In municipal solid
waste, small amounts of nickel are found in its ferrous fraction,
a fraction that varies from 7-10' percent of the total weight, depending on
geographic location and other variables.
Nickel can leach into nearby ground water supplies from landfills.
59
Chain and OeWalle • have recently analyzed various landfill leachates for
a vareity of constituents, including nickel, and report a range of nickel
values from <0.05 to 13.0ng/g. These results were from nine different
sources and represented a wide variety of conditions. The high value was
obtained from a newly-established lysimeter maintained under controlled
conditions so that leachates would be generated for a subsequent treatability
study. The low value was obtained from a simulated landfill in which the
leachate was recycled in order to study the attenuation of pollutants
through a landfill/ Certain other conditions such as temperature, pH,~
amount of moisture, and the ferrous content of the refuse itself play
a vital role in the amount of nickel in landfill leachates. Thus, there is
a rather wide range of values possible. Since landfill leachate has
the potential for contaminating a drinking water supply, good landfill
management is extremely important*
-------
DRAFT
CO NOT Q'JOTE OR
An alternate disposal procedure is incineration, commonly practiced
in many heavily populated areas of the U.S., particularly in the
Northeast. Here nickel can enter the environment by several paths:
volatilization through the stack effluent, entrainment in the
61
fly ash, o* collection with the incinerator residue. Jens and Rehn reported
on
the analysis of samples taken from several incinerators - (Taple 5.16).
£O
A more recent study by Achinger and Daniels cites the nickel
concentration of impinger-water residues as being<0.5 ppm for sample
number one and 0.5 ppm for sample number two. Sample one was from
particulates caught after the filter; it includes the residue left
after evaporation of the acetone used to rinse the sampling train
after the filter and before the impinger. Sample two was from the
residue left after evaporation of the chloroform and ether used to
extract organic materials from the impinger water wash.
-------
• DRAFT
Table 5.16. NICKEL IN INCINERATOR ASH61QQ NOT QUOTE OH CITE
Source Concentration, percent
Stack dust , 1 to 10+
Collector catch 0.001 to 0.01
Residue 0.001 to 0.01
-------
DRAFT
DO NOT QUOTE OR CITE
C«3
Buttermore, . et'al. 'recently reported the nickel content
for eight different municipal incinerator fly ashes. Reported as
percentage nickel by weight, the range of values was 0.04 to 0.01
with the majority being 0.02 percent or less. From these reported low
quantities, it appears that, at this time,nickel does not constitute
a major pollution problem. Further, it is assumed that modern air
pollution abatement equipment effectively removes most of the nickel
and its compounds,if they are present,in the gaseous effluents of
incineration.
In addition to entering the environment from disposal practices, nickel
is also observed in processes involving the recycling of solid waste.
64
Ostrowskl reports that induction and electric arc furnace heats
made with scrap from municipal incinerator residue showed that this
scrap contained considerable copper, tin, and nickel. Furthermore,
he maintains that use of incinerated ferrous scrap from solid waste
should be restricted to those steels whose specifications can
accommodate these critical impurities. Additionally, he states that
consideration must be given to the effect of the buildup of these
residuals in the system through recycling of domestic scrap. The
nickel percentage is reported at 0.100 for incinerated scrap, with
upper and lower confidence limits being 0.134 and 0.065 for the 95
percent confidence band. This compares favorably to the 0.11 percent Ni
55
determined for auto scrap by Carlson and Schmidt.
-------
DRAFT
DO f!OT QUOTE CR CITE
.Composting municipal solid waste has received much attention in
the past, and even today has some residual interest. Because of the
'.,-. • * '**.'„*
-.ferrous content and the accompanying shredding and grinding
operations, some metals are dispersed throughout the compost itself.
66
Recently, the United States Department of Agriculture analyzed three
compost samples for the presence of four heavy metal constituents; 7lnc, cadmium,
copper, and nickel. On a ug Ni/g dry weight basis, the three analyses yielded'16
24, and 25, respectively. By comparison, digested sewage sludge has showed a
range of 2b to 6,000 yg/g. presumably measured on a dry solids basis.
Therefore, it can be readily observed that the nickel content of the compost
was at the low end of sludge values, and should not present any major
toxicity problems.
s-s i
-------
ORAfTf
DO NOT QUOTE OR CITE!
5.4 REFERENCES F°R SECTION 5.
1. Nickel. National Academy of Sciences, Washington, D. C. Work
Performed Under Contract No. 68-02-0542. Environmental Protection
Agency, Research Triangle Park, N. C. 1974. 423 p.
2. Ironton, Ohio-Ashland, Kentucky-Huntington, West Virginia. Air
Pollution Abatement Activity. Pre-conference Investigation. U. S.
Department of Health, Education, and Welfare. Public Health Service
1968. 85 p.
3. Goldberg, A. J. A Survey of Emissions and Controls for "Hazardous"
and Other Pollutants. U. S. Environmental Protection Agency,
Research Triangle Park, N. C. Publication Number EPA R4-73-021.
February, 1973. 168 p.
4. National Inventory of Sources and Emissions. U. S. Environmental
Protection Agency, Research Triangle Park, N. C. Publication Number
APTD 69. February, 1970.
5. Personal communication with W. J. Rhodes. Control Systems Laboratory,
U. S. Environmental Protection Agency, Research Triangle Park,
N. C. April, 1974.
6. Thurr, G., "Potential Health Hazard of Nickel Compound Emissions
from Automotive Gas Turbines", AAPS Coordination Meeting, Ann Arbor,
Michigan. May 14, 1974.
7. Castantinides, G., and Arch, G., Fundamental Aspects Petrol.
Geochemistry, 1967, 109-75.
8. Baker, E. W., J. Chem. Eng. Data, 9_:307 (1964).
-------
;:0 fttfQUQTE OR GITE
9. Ward, C. C., (U. S. Bureau of Mines). ASTM Spec. Tech. Publication,
No. 531, p. 133-42 (1973).
10. (a) Bernstein, L. S. et al., SAE Paper No. 730567, Detroit, Michigan,
May 14, 1973.
(b) Jackson, H. P., McArthur, D. P., and Simpson, H. D., SAE Paper
No. 730568, Detroit, Michigan, May 14, 1973.
11. In-House EPA data.
12. Gentel, J. E., Manary, 0. J. and Valenta, J. C., Report on
EPA Contract EHS-70-101, APTD-1567, Dow Chemical Company, March 1973.
13. Exxon Research Engineering, Monthly reports on EPA contract
No. 68-02-1279.
14. Test Procedures for Vehicle Exhaust and Evaporative Emissions. Fed.
Register. 37J221):24, 250. Nov. 15, 1972.
15. Test Procedures for Vehicle Exhaust and Fuel Evaporative Emissions.
Fed. Register. 35(219): 17294-17303. Nov. 10, 1970.
16. Data stored in the National Aerometric Data Bank, U. S. Environmental
Protection Agency, Research Triangle Park, N. C. 1974.
17. Preliminary Results of Contract No. 68-01-0438. U. S. Environmental
Protection Agency, Research Triangle Park, N. C. with MITRE Corp.
Virginia.
18. Coal Data. Control Systems Laboratory. U. S. Environmental Protection
Agency, Research Triangle Park, N. C. 27711. 1.,.
19. Lee, R. E., Jr., S. S. Goranson, R. E. Enrione, and G. B. Morgan.
National Air Surveillance Cascade Impactor Network, II. Size
Distribution Measurements of Trace Metal Components. Environ.
Sci. Technol. 12:1025, November 1972.
5~S3
-------
I ft »• »• •
3 NOT QUOTE OR CITE:
20. Kopp, J. F., and R. C. Kroner. Trace Metals in Waters of the United
States: A Five Year Study of Trace Metals in Rivers and Lakes of
the United States, October 1, 1962 to September 30, 1967. U. S.
Department of the Interior, Federal Water Pollution Control
Administration, Division of Pollution Surveillance, Cincinnati
Ohio. 48 p.
21. Cannon, H. Trace Elements Excesses and Deficiencies in Some
Geochemical Provinces of the United States. In: Trace Substances
In Environmental Health. Hemphill, D. D. (ed.), Columbia, Mo.
University of Missouri Press. "1969.
22. Mitchell, R. L. Cobalt and Nickel in Soils and Plants. Soil Set.
60:63-70, 1945.
23. Vanselow, A. P. Nickel in Diagnostic Criteria for Plants and
Soils. H. D. Chapman (ed.), Riverside, Calif. Publisher, 1966.
24. Klein, H. Mercury and Other MEtals in Urban Soils. Environ.
Sci. Techno!. 6;560-562. 1972.
25. Yost, K. J. , W. Bruns.,"J. E. Christian,~ FV MT'Clikeman,
R. B. Jacko, D. R. Masarik, W. W. McFee, A. W. Mclntosh,
J. E. Newman, R. I. Pietz, and A. M. Zimmer. The Environmental
Flow of Cadmium and Other Trace Metals. Vol. 1. NSF (RANN) Progress
Report, July 1, 1972 to June 30, 1973. National Science Foundation
(RANN), Washington, D. C.
26. Lagerwerff, J. V. and A. W. Specht. Contamination of Roadside Soil
and Vegetation with Cadmium, Nickel, Lead and Zinc. Environ. Sci.
Technol. 4:583-586, 1970.
27. Peterson, P. J. Unusual Accumulations of Elements by Plants
and Animals. Sci. Prog. Oxf. 59_: 505-526, 1971.
-------
DRAFT
DO MOT QUOTE OR CITE
28. Zajic, James E. Microbial Biogeochemistry. Academic Press, New
York. 1969. 345'p.
29. Ehrlich, H. L. Microbial Transformations of Minerals: In:
Principles and Applications in Aquatic Microbiology. Chapt. 3.
1964.
30. Nomoto, S., arid F. W. Sunderman. Atomic Absorption Spectrometry
of Nickel in Serum, Urine and Other Biological Materials. Clin. Chem.
16j_477-485, 1970.
31. Sunderman, F. W., M. I. Decsy, and M. D. McNeely. Nickel Metabolism
in Health and Disease. Ann. N. Y. Acad. Sci. 192:300-312, 1972.
32. Perry, H. M., I. H. Tipton, H. A. Schroeder, and M. J. Cook.
Variability in the Metal Content of Human Organs. J. Lab. Clin.
Med. 60:245-253, 1962.
33. Tipton, I. H. Distribution of Trace MEtals in the Human Body.
In: Metal Binding in Medicine, M. J. Stevern and L. A. Johnson.
Philadelphia, Lippincott, 1960. p. 27-42.
34. Tipton, I. H., M. J. Cook, R. L. Steiner, C. A. Boye, H. M. Perry,
Jr., and H. A. Schroeder. Trace Elements in Human Tissue. Part I.
Methods. Health. Phys. 9_:89-101. 1963.
35. Nechay, M. W. and F. W. Sunderman. Measurements of Nickel in Hair
by Atomic Absorption Spectrometry. Ann. Clin. Lab. Sci. 3_:30-35,
1973.
•""36. Schroeder, H. A., and A. P. Nason. Trace Metals in Human Hair.
J. Invest. Derm. 53_:71-78, 1969.
37. Horak, E., and F. W. Sunderman. Fecal Nickel Excretion by Healthy
Adults. Clin. Chem. 19:429-430, 1973.
-<5 S
-------
DRAFT
HO NOT QUOTE OR CUE
38. Hohnadel, D. C., F. W. Sunderman, M. W. Nechay, and M. D. McNeely.
Atomic Absorption Spectrometry of Nickel, Copper, Zinc, and Lead
in Sweat Collected from Healthy Subjects During Sauna Bathing.
Clin. Chem. 19.: 1288-1292, 1973.
39. McNeely, M. D., M. W. Nechay, and F. W. Sunderman. Measurements
of Nickel in Serum and Urine as Indices of Environmental Exposure
to Nickel. Clin. Chem. 18.:992-995, 1972.
40. Allaway, W. H. Agronomic Controls over the Environmental Cycling
of Trace Elements. Adv. Agron. 2£: 235-274, 1968.
-------
DKAVI
DO NOT QUOTE
^ • Chaney, R. L. Crop and Food Chain Effects of Toxic Elements in
Sludges and Effluents. In: Recycling Municipal Sludges
and Effluents on Land. Washington, D.C. National Association
of State Universities and Land Grant Colleges, 1973. p. 129-141.
42. Hal stead, R. L. Effect of Different Ammendments on Yield and
Composition of Oats Grown on a Soil Derived from Serpentine
Material. Canadian J. Soil Sci. 48:301-305, 1968.
43. Lindsey, W. L. Inorganic Reactions of Sewage Wastes with Soil.
In: Recycling Municipal Sludges and Effluents on Land.
Washington, D.C., National Association of State Universities
and Land Grant Colleges, 1973. p. 91-96.
44. Tiffin, L. 0., J. V. Lagerwerft, and A. W. Taylor. Heavy Metal
and Radionuclide Behavior in Soils and Plants - a Review.
Performed by U.S. Dept. of Agriculture, Beltsville Agriculture
Research Center for the Division of Biomedical and Environmental
Research, U.S. Atomic Energy Commission, Washington, D.C.
under A.E.C. Research Contract AT(49-7)-l. 1963. -p.
45. Halstead, R. L., B. J. Finn, and A. J. McLean. Extractability
of Nickel Added to Soils and Its Concentration in Plants.
Canadian J. Soil Sci. 49_: 335-342. 1969.
46. Pratt, P.,F. F. Bair, and G. W. McClean Reactions of Phosphate
with Soluble and Exchangeable Nickel. Soil Sci. Soc. Amer.
Proc. 28:363-365. 1964.
47. Mortensen, J. L. Complexing of Metals by Soil Organic Matter.
Soil Sci. Soc. Amer. Proc. 27:179-186. 1963.
-------
DRAFT
DO NOT QUOTE OR CUE
48. Pratt, P. F., F. Bair, and G. W. McClean. Nickel and Copper
Chelation Capacities of Soil Organic Matter. Eighth Int.
Cong. Soil Sci., Buchanest, Romania. Transactions 3:243-248.
1964.
49. Junge, C. Comments on Concentrations and Size Distribution
Measurements of Atmospheric Aerosols and a Test of the Theory of
Self Preserving Size Distribution. J. Atmos. Sci. 2^:603-608, May
1969.
50. Hidy, G, M. The Dynamics of Aerosols in the Lower Troposphere.
In Assessment of Aerosols, Mucer, T. M., P. E. Morrow, and V. Stober
(eds.). Springfield, 111., Charles C. Thomas Publisher, 1972. p. 81-115,
51. Severne, B. C. Nickel Accumulation by-Kybahthus^-f1oriBundus. Nature
248_:807-S08. 1974.
52. Gish, Charles D., and Robert E. Christensen. Cadmium, Nickel, Lead
and Zinc in Earthworms from Roadside Soil. Environ. Sci. and Tech
7; 1060-1062., 1973.
53. Prince, A . L. Trace Element Delivering Capacity of 10 New
Jersey Soil Types as Measured by Spectrographic Analysis of Soils
and Mature Corn Leaves. Soil Sci. 83_:413-418. 1957.
b'4. Tyler, G. Moss Analysis - A method for Surveying Heavy Metal
Deposition. Proc. Second Int. Clean Air Congr. Washington, D. C.,
Academic Press, 1971. ' ]29-132
-------
^o
^J ^l.>UiL ui<
55. Tyler,G . Heavy Metals Pollute Nature, May Reduce Productivity.
Ambio. 1:52-59, 1972.
56. Gupta, R. S. On Some Trace Metals in the Baltic. Ambio. 1:226-230.
1972.
57, Goldberg, E. D., W. S.Broecker, H. G. Gross, K. K. Turekian. Marine
Chemistry. Chapter V In: Radioactivity in the Marine Environment.
National Academy of Sciences, Washington, D. C. 1971.
58. Bowen, V. F., J. S. Olsen, C. L. Osterberg, and 0. Ravera. Ecological
Interactions of Marine Radioactivity. In: Radioactivity in the
Marine Environment. NAS. Chap. 3 pp. 2CO-222. 1971
59. Chain, E. S. K., and F. DeWalle. Treatment of Leachate Generated
from Landfills. First Annual Report. University of Illinois.
Work done under Contract 68-03-0162 for the U. S. Environmental
Protection Agency, Solid and Hazardous Waste Research Laboratory.
'1973. p.
60. Pohland, F. G. Landfill Stabilization with Leachate Recycle. Georgia Institute
of Technology. !«'ork done under Project MO. FP-n^65R. !!. S. Fnvironmental
Protection Agency, Solid and Hazardous Waste Research Laboratory. Cincinnati,
ft* Jens', W. cihd F. R. Rehn. Municipal Incineration and Air Pollution
Control. In: Proceedings of 1966 National Incineration
New York.
ConferenceyThe American Society of Mechanical Engineers.
1966. p. 74-83.
62. Achinger, W. C.,and L. E. Daniels. An Evaluation of Seven
Incinerators. U.S. Environmental Protection Agency,
Cincinnati, 0. Publication SW-51fs.lj, 1971.
-------
DFAFT
. ... .- .-•* '"• r* » "f* T™1
P- .-- Fi'r-.-r •••;:••: ' . ; r \TU
U; i\i;i ^.,^M: v,-. -...siL
63. Buttermore, W. H., £t al_. Characterization, Beneficiation and
Utilization of Municipal Incinerator Fly Ash. In: Proceedings
of the Third Mineral Waste Utilization Symposium, U.S. Bureau
of Mines and Illinois Institute of Technology Research
Institute. 111. March, 1972.
64. Ostrowski, E. J. Recycling of Tin Free Steel Cans, Tin Cans
and Scrap from Municipal Incinerator Residue. Presented:
79th General Meeting of American Iron and Steel Institute.
New York, N.Y. May 26, 1971.
65. Carlson, 0. N. and F. A. Schmidt. The Metallurgical Upgrading
of Automotive Scrap Steel. Iowa State University. Worl< done under grant
No. R-801303. U.S. Environmental Protection Agency,
Cincinnati, 0. Final Project Report, May 1973.
66- Chaney, R. L. Letter to Robert Burns, AENCO. United States
Department of Agriculture, June 1973.
-------
6. ENVIRONMENTAL EXPOSURE
6.1 MULTI-MEDIA EXPOSURE
6.1.1 Ambient Air
Nickel is emitted into the ambient air from a variety of sources.
Emission factors for a number of source types are presented in Tables
6.1 to 6.4. An emission factor is an estimated average of the rate at
which a pollutant is released to the atmosphere as a result of some
activity, divided by the level of that activity. The nickel emission
factors can be used to estimate emissions for a given community. The
extent to which the nickel concentrations present in ambient air pose
a hazard for human health is at present unknown.
As previously discussed, nickel mining and ore processing plants
are major sources of nickel emissions to the atmosphere. Another source of
nickel in ambient air is the combustion of fuel oil for space heating.
In densely populated urban areas during winter months, fuel with the
latter concentration level could produce considerable quantities of air-
borne nickel. It has been estimated that in Manhattan, where 14.8
million liters of fuel oil are used per year, allowing a nickel content
of 10 ppm and an emission rate of 25 percent, the daily release rate of
nickel into the atmosphere would be 156 kg during the cold weather months.
Coal-fired power plants are another stationary source of nickel.
The content of nickel in coal varies according to the region in which
the coal was produced: midwestern states, 0.025 kg/MT; eastern states,
3 •
0.016 kg/MT and western states 0.004 kg/MT. Not all of the nickel
-------
content of coal is emitted to the atmosphere; however, evidence does
indicate that nickel is present in increasing proportions as the size
of the coal ash decreases. Thus, the finely divided ash has a higher
percentage of nickel present and is more likely to reach the human
4
respiratory tract. Certain types of boilers in coal-fired power plants
(the spreader stoker, the cyclone fired unit, and the horizontally
opposed types) produce a higher nickel content in ash than others.
The National Air Surveillance Networks (NASN) monitored air
quality in thirty cities in the United States. From 1957 to 1968,
the average nickel concentrations declined slightly from 0.047 yg/m
3
to 0.026 yg/m among the NASN monitored cities. Cities having the
highest airborne nickel concentrations were East Chicago, Indiana
(0.132 yg/m3); Boston, Massachusetts (0.112 yg/m3); and New York City
o
(0.118 yg/m ). The cleanest cities, having no detectable nickel
present in the air, were: Boise, Idaho; Albuquerque, New Mexico; and
Moorhead, Minnesota.
Both urban-rural differences and seasonal differences in airborne
nickel concentrations exist; the urban areas have the most nickel in
the air during fall and winter months.
-------
6.1.2 Water
As indicated previously, the nickel concentration in U. S.
surface and ground water is quite low. Data regarding the nickel
concentration in drinking water actually consumed by man are limited.
Samples collected at water plants do not reflect the pickup of metals
from the distribution system. The EPA National Environmental Research
Center at Cincinnati, Ohio conducted an extensive study of metal
pickup in distribution within the Chicago supply. When the distribution
samples were compared with samples collected at the treatment plant,
it was noted that 34 percent showed an increase in the nickel content
of the water. A Community Water Supply Survey was conducted in eight
metropolitan areas in 1969-70. These included samples from 969 water
supplies. The average nickel concentration in the water samples taken
at the consumer's tap was 4.8 yg/liter. With an estimated consumption of
two liters per day, the nickel intake via water for an adult would be
approximately 10 yg/day.
Nickel was found in 78'percent of the samples with a minimum level of
1 ug/liter Using these data, Table 6.1 shows the frequency distribution
o
of nickel in drinking water.
4-3
-------
I > I
•I
Table 6.1. NICKEL IN DRINKING WATER,,
, COMMUNITY WATER SUPPLY SURVEY
D0
o«
lligrnms
Liter
•
.001 - .
.006 - .
.011 - .
.016 - .
.021 - .
.026 - .
.031 - .
.036 - .
..041 - .
.046 - .
.051 - .
•
per
000
005
010
015
020
('
025
030
035.
040
045
050
055
075
Number of
Samples "
543
1082
640
167 •
• ' 46 -<
' 14
4
2
1
1 •
': '1
1
1
Percent of
Samples
21.69
43.22 •
25.57
6.68
1.84.'
.56
.16
.08
.04 .
.04
.04
.04
.04
1 S\ y"v i*i s\
2503
.?'•
-------
x
8
McNeely et a"i . " examined the tap water in two communities to
determine the nickel concentration. The communities were Hartford,
Connecticut, an area free from nickel industries; and Sudbury, Ontario,
a center for nickel mining and processing. The mean concentration of
nickel in five samples from Hartford was 1.1 - 0.3 yg/liter. The
mean nickel concentration in Sudbury was 200. - yg/liter.
6.1.3 Food
The information available indicates that the concentration of
nickel in foods is low and does not pose a toxicity problem.
Among the common foods for which the nickel content has been
ascertained, the following have relatively high levels of Ni : baking
powder, 13.4 ug/g;orange pekoe tea, 7.6 yg/g; buckwheat seed, 6.5 .v9/?»
cocoa, 5.0 yg/g,gelatin, 4.5 Mg/g; black pepper, 3.9 ug/a; mushrooms,
3.5 yg/g; cabbage, 3.3yg/q;red kidney beans, 2.6 yg/g; oats, 2.4 yg/g;
and shortening, from 2.0 to 6.0
The nickel -containing stainless steels used for food processing
equipment are thought to contribute only minute amounts of metal; "trace
quantities having no pharmacological significance."
Exposure of animals other than humans to nickel is also dependent
on their choice of food plants. In the case of domestic animals it
will be principally through the nickel present in pasture grasses and
feed grains.
PI ants whether they are used for food or not, may be exposed to
nickel in air, water or ' soil. Aerial exposure
-------
is principally caused by nickel dust from industrial processes and motor
11 12
vehicles being deposited on vegetation and soil. ' or entering
aquatic habitats. The extent to which plant exposure to nickel may
occur ,is dependent on the extent to which nickel deposition increases
the concentration in the specific medium, such as, the soil. Applications
of sewage sludge to soil may increase the nickel levels and therefore,
plant exposure. Phosphate fertilizers also contain nickel as do certain
pesticides. Applications of either of these substances may
increase the possibility of exposure to nickel.
6.1.4 Soils
As indicated in other sections of this document,the nickel content
of soils varies considerably from one area to another. The amount
depends upon several factors and has been reported by a number of
13
investigators to range from less than 50 g/g to 500yg/g. ' The higher
concentrations usually occur in soils derived from serpentine rocks
where concentrations as high as 5000yg/g have been reported, whereas
50yg/qor less is normal for soils derived from sandstones, limestones,
and acid,igneous rocks.
Any discussion of trace metals in soils should probably distinguish
between native trace metals and those that are added to soils. Pollution
effects from trace metals in soils are more often associated with the
added metals rather than the native ones. An exception, of course,
has been the toxicity of nickel to plants growing on high nickel-containing
13 14
serpentine soils. ' This circumstance arises because the form in
which the trace metals are added is different from the native metals
which have normally reached a state of equilibrium with the surrounding
soil and associated conditions.
-------
ORAFT
DO MOT QUOTE OR CITE
12 "
Lagerwerff and Specht founa 'detectable amounts of nickel at sites near
dense automative traffic areas, presumably from the use of nickeled
gasoline and atmospheric abrasion of nickel-containing automobile parts.
The concentration gradient of the n1ckel and other trace metals
studied in the soils and vegetation decreased with distance from the
road, indicating that the road traffic was the source of the pollution.
The nickel concentrations, however, were extremely small and probably
not significant with regard to pollution of the soils. Nickel
13
has been used in selected fungicides and is usually present in pulverized
15
serpentine, which may be used as a source of available mannanese. Although
two uses
these/may represent potential sources for nickel contamination of
soils*there is little available evidence to suggest that these must
be considered as important sources of nickel contamination of soils.
nickel
However, soils near/ mining areas can be expected to contain toxic
levels of nickel. The ash from coal-fired power generating plants
may contain significant quantities of nickel. Depending upon the
technique used to manage the fly ash, some pollution of surrounding soils
and associated ground waters could occur. Little evidence has been
developed, however, to permit proper assessment of the situation.
More than 200 ppm of water soluble nickel was reported in soils three
I r 'y
miles from smelters located in the Sudbury Basin in Ontario.
t-7
-------
DRAFT
DO NOT QUOTE OR CITE
Although the mechanisms mentioned are potential sources for nickel
contamination of soils, available evidence suggests that these
are not significant, except perhaps in the localized areas in close
proximity to the source.
The application of urban waste to lands for reasons of land and
crop management and for waste management is not new. Since one of
the most pressing problems facing metropolitan areas is disposal of
large volumes of liquid and solid wastes, this technique is receiving
-17
widespread attention as a disposal method. Many materials added to
soils may contain toxic heavy metals. Sewage sludge contains zinc, copper, nickel,
and cadmium in excess of soil levels. The sludge and effluent
are applied to soil with the intent that the toxic elements be
retained by the soil. Since these elements will accumulate and
persist, they are a potential long term environmental hazard with
regard to the land application of urban wastes. Thus this appears
to be potentially the greatest source for nickel contamination of
soils. Sludges from several different areas were found to contain
17 IP. IP.
relatively high concentrations of nickel. ' Chaney suggests
that because of the amounts of toxic metals,including nickel, contained
in sludges from many large treatment plants treating municipal and
industrial wastewater, from small plants serving only a few
from
unregulated metal industries, and even/a few serving domestic sources,
many sludges ^ould be prohibited from being applied to soils. This
-------
DRAFT
DO NOT QUOTE OR CITE
was based upon his review of available sludge analysis data, results
of his own analysis of sludges from several areas, and the application
of certain assumptions and factors with regard to soil conditions,
metal content, etc. Sludges from the operating digesters of several
cities ranged from < 50 mg/kg dry sludge in cities with little or no
heavy metal producing industries to as high as 1100 mg/kg dry sludge
in cities with moderate to relatively large amounts of heavy metals
producing industries.
6.1.5 Occupational
Though the safety of the work environment is much better today than
it was previously, there are still some industries for which sufficient
19
monitoring of the workroom air has not been undertaken.
6.2 RECEPTOR RISKS
Since nickel is present in natural waters, soils, and foods, man
is inevitably subject to oral, inhalation and cutaneous exposures to
trace amounts of nickel. The probability of exposure to nickel carbonyl,
the most, toxic of all known organic nickel compounds, is limited primarily
to cases of occupational exposure. There is n
-------
L/ixru i
DO NOT QUOTE OR CITE
The addition of sewage sludge to agricultural soil may increase the
risk of exposure of plants to nickel. Based upon Chaney's recommendations,
a sludge containing only 300 mg/kg dry sludge of nickel would be a conditional
sludge for application to soils of a cation exchange capacity equal to
18 .
10. - This suggests that as many as 30 to 60 percent of the sludge for
\
which data is available could not be applied to soils based upon metal
content and today's knowledge of the ultimate fate of the metals in the
soils and plants. Only 25 to 50 percent would be recommended.
There have been numerous examples of metal toxicity in agriculture
crops, some directly related to the application of sludge and effluent. ?ns??
Much of this has already been related to poor land management.
In the case of the application of typical domestic sludge to land, it
would appear that mercury, cadmium, zinc, and copper, in that order, may
become limiting relative to potential toxic concentrations before nickel
and chromium cause problems. Sludges from metropolitan areas with large
industrial inputs may contain concentrations of nickel and chromium
that are so large that these elements may become the controlling factor
with regard to soil toxicity and resulting toxicity to sensitive plants.
Since selected factors such as organic matter, phosphate, and other
factors control the accumulation of toxic metals, including nickel, in
soils and crops, proper management of the receiving soils and observance of
certain application techniques will play an important role in controlling
the application of sludges, effluents, compost and other wastes to the
soils so that toxicity to the soils and crops will be manageable.
18
Chaney discussed this and suggested that two bases Be used for formulating
-------
DRAFT
recommendations for the addition of toxic metals (in sludges, effluent,
compost, etc.) to agricultural soils. These are: a benefit: risk ratio,
and a limitation of metal additions to permit contained general farming.
Since nickel has been found in sludges, effluents, and compost in quantities
sufficient to cause toxicity problems in soils and plants, caution must
be exercised in applying these wastes to the soils. In order that
this caution be properly exercised, studies must continue to provide
knowledge and data not now available with regard to such factors as
crop species and varietal differences in tolerance and accumulation
,of toxic metals; reversion of toxic metals in different soils; effects
of organic matter, phosphate, etc.; basic knowledge on crop and
management effects on soil organic matter as it relates to control of
excess copper, nickel, and zinc. Further, almost nothing is known about
toxic metal interactions and the importance and mechanisms of phosphate
interaction with zinc, copper, nickel, cadmium, lead, and mercury.
to alleviate toxicity and prevent plant transport of these toxic
4. *°
elements. ^ -
Exposure of aquatic plants and animals to detrimental levels of
nickel will depend on the concentrations in the water where they exist.
&-'/
-------
DRAFT
W NOT QUOTI '
6.3 REFERENCES FOR SECTION 6,
1. Anderson, D. Emission Factors for Trace Substances. U.S.
Environmental Protection Agency, Research Triangle Park, R,^6; Publication
No. EPA-450/2-73-001. December 1973
2. Nickel, National Academy of Sciences, Washington, D. C. Work
Performed Under Contract No. 68-02-0542 for U.S. - Environmental
Protection Agency , Research Triangle Park, N. C. 1974. 423 p.
3. Cuffe, S, 7.,'and R. W. Gerstle. Em1ss1pns From Coal-fired Power
Power Plants: A Comprehensive Summary. .Public ftealth Service, National
Center for Air Pollution Control, Cincinnati. PHS Publication No. 999*AP-35.
1967. 30 p.
4. Natusch, D.F.S., J.R. Wallace, and C. A. Evans, Jr. Toxic Trace
Elements: Preferential Concentration 1n Resplrable Particles.
Science. 183:202-204, 1974.
5. Abernethy, R. F. and F. H. Gibson. Rare Elements in Coal. U.S. Department
Washington,D.C.
of the Interior, Bureau of Wines,/Bureau of Mines Information Circular
"No. 8163. 1963. 69 p. '
-------
6- McMullen, T. B. Concentrations of Nickel in Urban Atmospheres--
1957-1964. U. S. Department of Health, Education
and Welfare, Public Health Service, Robert A. Taft Sanitary
Engineering Center, Cincinnati: 1966. 17. p.
7. Air Quality Uata from tne National Air Surveillance Networks and
Contributing State and Local Networks. 19bb Edition. "U.S: Department
of Health, Education, and Welfare. National Air Pollution Control "'. "
Administration, Publication No. APTD 68-9. Durham, N. C.: 1968.
157 p.
8- McNeely, M. D., M. W. Nechay, and F. W. Sunderman, Jr. Measurements
of Nickel in Serum and Urine and Indices of Environmental Exposure
to Nickel, 'ciin. Chem. 18^:992-995, 1972.
9- Schroeder, H. A., J. J. Balassa, and I. H. Tipton. Abnormal Trace
Elements in Man—Nickel. J. of Chronic D1s. 15:51-65, 1962.
10. Lehman, A. J. Culinary Stainless Steels. Association of Food
Drug Officials. U. S. 25:123-127, 1961.
11- Klein, David H. Mercury and Other Metals in Urban Soils. Environ.
SciJechnol. 6_: 560-562, 1972.
12- Lagerwerff, J. V. and A. W. Specht. Contamination of Roadside
Soil and Vegetation with Cadmium, Nickel, Lead and Zinc. Environ.
Sci. Techno!. 4:583-586, 1970.
-------
13. Halstead, R. L., B. J. Finn, and A. J. Maclean. Extractabllity
of Nickel Added to Soils and Its. Concentration in Plants.
Can. J. Soil. Sci. 49:335-342, 1969.
T4. Aderson, A. J., D. R. Meyer,and F. K. Mayer. Heavy Metal Toxicities:
Levels of Nickel, Cobalt, and Chromium in the Soil and Plants
Associated with Visual Symptoms and Variation in Growth of an
Oat Crop. Aust. J. Agric. Res. 24_:557-71, 1973.
15- 'Burns, A. F.,and A. M. Smith. Pulverized Serpentine as a Source
of Available Magnesium- Presented at the Joint Meeting of the Northeast
Branch of the Americal Society of Agronomists, Canadian Society of Soil
Science, and Canadian Society of Agronomists, Ottawa,
Ontario, Canada. 1965.
16. Costescu, L. and T. C. Hutchinson. Air-borne Metallic Contamination
of Soils in the Sudbury Area, Ontario. Agronomy Abstracts 1970
17. Page, A. L. Fate and Effects of Trace Elements in Sewage Sludge
When Applied to Agriculture Lands: A Literature Review Study. Department
of Soil Science and Agriculture Engineering, University of California.,
Riverside, California.
18. Chaney, R. L. Crop and Food Chain Effects of Toxic Elements in
Sludges and Effluents. In: Recycling Municipal Sludges and
Effluents on Land . Washington, D. C. National Association of State
Universities and Land Group College, p. 129-141.
19. Threshold Limit Values for Chemical Substances and Physical Agents
in the Workroom Environment. Cincinnati, Ohio, American Conference
of Governmental Industrial Hygienists, 1972. 94 p.
-------
DRAFT
NOT QUOTE OS CITt
20. Voss, R. C., and H. Nicol. Metallic Trace Elements in Tobacco.
Lancet. 2^:435-436, 1960.
21. Sunderman, F. W., and F. W. Sunderman, Jr. Nickel Poisoning.
XI. Implication of Nickel on a Pulmonary Carcinogen in Tobacco
Smoke. Amer. J. Clin. Path. 35:203-209, 1961.
22. Hueper, W. C. Carcinogenic Hazards from Arsenic arid Metal Containing
Drugs. In: Potential Carcinogenic Hazards from Drugs. Evaluation
of Risks. Truhart, R. (ed.). Berlin, Springer-Verlag, 1967.
23. Letter to Sludge Disposal Work Group. United States Environmental
Protection Agency, Cincinnati, Ohio. Subject: Comments on submitted
section 1.3.1.2 from United States Department of Agriculture,
February, 1974.
24. Patterson, J. B. E. Metal Toxicities Arising from Industry. Trace
Elements in Soils and Crops. Min. Agr. Fish. Fed.Tech. Bull.
21:193-207, 1971.
-------
DRAFT
DO NOT Q" "1 CITE
7. MECHANISMS OF EXPOSURE
7.1 ANIMAL
7.1.1 Routes of Intake and Absorption
7.1.1.1 Routes of Animal Exposure—Routes of exposure of man and other
animals to nickel are essentially the same with differences, perhaps,
in relative magnitude of importance. The routes of exposure of animals
in order of importance, are: ingestion, inhalation, absorption,
anci parenteral administration.
7.1.1.1.1 Ingestion--Tedeschi and Sunderman have determined that nickel
ingestion averages 373 yg/day in dogs fed a major brand of^pg food ad libitum.
Except in unusual circumstances, intake of nickel by domestic animals
by any means other than ingestion would be negligible.
2
7.1.1.1.2 Absorption—Schroeder et al. have suggested that mammals
possess mechanisms that limit intestinal absorption of nickel.
Feeding experiments using dogs suggest that 10 percent of soluble nidel is
absorbed. Higher absorption in dogs than in man might be expected due
to the relatively low pH of the canine gastric juices.
7.2 HUMAN
7.2.1 Oral Intake
It has been estimated that the nickel content of food and water
2
ingested by human beings ranges from 300 to 600 yg per day. However,
most of the nickel content of the diet passes through the gastro-
intestinal system unabsorbed.
1-1
-------
DRAFT
DO NOT QUOTE OR CITE
7.2.2 Percutaneous
The quantity of nickel absorBed through the skin is proBaBly neg-
ligiBle, This route is of clinical significance Because of nickel
3
dermatitis.
7.2.3 Parenteral Admin is tea tloiL
The nickel content of stainless steel prostheses and implants has
4
become a problem in terms of incurring hypersensitivity to the metal.
Here, again, the quantities of nickel leached from the items by body
fluids are negligible.
7.2,4 Inhalation
The estimated quantities of nickel inhaled b^ a resident of one of the
cities: having the Highest measurements of nickel in ambient air are
2,36 yg/day in New-York City, or 13.8 yg/day in East Chicago. The average
daily intake of nickel by urban residents is 2-14 yg/ per day, depending
upon the season and the location, 5
The production of nickel -cadmium batteries, and nickel
electroplating are industries which may involve hazards from nickel dust.
Steel mills are also potential sources of nickel emissions but have not
been evaluated in this report.
7.2.5 -Special Categories
7.2.5.1 Smoking--The mean nickel content of cigarettes has been found
to range from 2.0 to 6.2 yg/cigarette.6'-7 Studies have demonstrated that 10 to
20 percent> of the nickel in cigarettes is released in mainstream smoke.
Of the nickel present in smoke, 84% is in gaseous phase, and 16 percent is in
particulate phase. There is some evidence that the gaseous nickel in
cigarette smoke is in the form of nickel carbonyl. Thus, a smoker who
consumes two packages of cigarettes per day will inhale a maximum of 14.8 yg of
£
nickel per year. . 1-2^
-------
rv,
00
QUOTE OR CITE
American pipe tobacco, cigars, and snuff have been found to contain
Q
2-3 yg of nickel per gram of tobacco. Cigars and snuff from other
countries have even higher nickel content. The wrappings around the
cheaper brands of cigars are made from tobacco leaves treated in such a
way that the content of inorganic particles is high, though the amount of
nickel present has not been ascertained.
7.2.6.2 Nedica-lNftppliances—^Nickel bearing surgical implants and
specially designed prosthetic devices in direct contact with the human
body for long periods of time may corrode at rates sufficient to produce
10
toxicity,,.
y.2.b.3 x&tner^&iyjronmeiitaJxStources-^-Among other possible sources of
nickel contact exposure are inexpensive Jewelry, coinage, clothing
fasterners, tools, cooking utensils, stainless steel kitchen equipment,
and detergents.
1-
-------
DRAFT
DD r'0T QUOTE OR CITE
7.3 PLANTS AND ORGANISMS
Exposure of terrestrial plants to nickel occurs chiefly through the roots,
The root hairs are the avenue through which nickel enters the plant,
and then only when in solution. When in solution, nickel may move across
the cell membranes in the root hairs and then move into the root proper.
From there it can be translocated throughout the plant in the xylem sap.
Uptake of nickel by plants depends on the
concentration of nickel in the soil, the type and nutritional status
of the plant, and, even more importantly ihe availability of nickel.
The pH, chemical binding, solubility, presence*and composition of other
elements and the organic composition of the soil all are important in
determining the availability of nickel. The organic composition of
soil and litter is an important factor because it affects ion exchange. The
negatively charged organic ions are capable of binding metallic ions
and holding them in a form which is not readily available. Microbial
action and the importance of Eh in nickel uptake seems not to have
been studied.
Exposure of plants to nickel in urban industrial areas and along
highly traveled highways may occur through the deposition of airborne
nickel on the plant surfaces. The extent to which the nickel bearing
dust is retained on plant surfaces is dependent to a great extent on the
growth form of the plant and leaf morphology. Foliar penetration of the
leaf by nickel may occur if it is in solution. Studies showing foliar
penetration by nickel in solution are few and deal chiefly with nickel
containing pesticides. Studies exist which indicate that trace elements,
-------
DRAFT
such as DO NOT QUOTE OR Cffl
iron, manganese, zinc, copper,molybdenum,and cobalt, are rapidly
11 «*
absorbed from the leaf surface, .wtter. foliar absorption, the element
may be moved about the plant or remain in the leaf.
Deposition of nickel onto the surface of mosses results in its
1 ? 13
being taken up through ion exchange. "-' The degree of sorption between
the simple cations of heavy metals and negatively charged organic groups in most
moss tisues is: calcium and lead> nickel> cobalt^.cadmium,> zinc andananganese.
The sorption of
nickel by mosses and lichens does not necessarily mean that it is taken
into the moss or lichen tissues, but it does favor an accumulation in dead
1< 7 , .
organic matter, litter and humus." Table '•.'shows the concentrations
of nickel in a spruce forest in Sweden.
Microorganisms growing on the leaves, other plant surfaces,and in
the soil may be exposed to nickel in particulate form when it is deposited
on the plant and soil surfaces. For exposure to occur,the nickel solution
must come into contact with the cell membrane of the microorganisms.
Aquatic plant species are exposed to nickel either through their cell
membranes or in the case of higher plants through their root systems.
Exposure of aquatic animals may occur either through the ingestion of
vegetable matter or through the circulation of water through their systems.
-------
Table 7 1. CONCENTRATION OF NICKEL iN
SWEDEN (mg/kg dry weight)
FOREST IN CENTRAL
Nickel
Spruce (Picea abies) '"• •"•:•• "'••; ,:
roots Ommdlam , "
>5mm »
wood
bark
twigs, 1st year
2nd »
3rd »
4th »
5th— 7th year
needles, 1st year
2nd »
3rd »
4th >
5th— 7th year
needle litter
Cowberry -(Paec/nium vili.f idaea)
above ground biomass
Bilberry (I'accinium myrtilliis)
above ground biomass
Hairgrass (Dcscliatnpsia flexuosa)
leaves
leaf litter
rools-f rhizomes
I;pipliytic lichens (Parmclia physodes)
Mosses (Hypniiin cu press! forme)
7.6
5.8 --
0.5
2.5
14
13
13
10
6.1
3.8
3.4
2.5
3.0
3.2
26
6.2
4.8
12
14
13
18
52
'.•'•'.' '-••" '•"' >
(25) a
'-::•• d5) :,•;;. '.\
(2.3)
(4.4)
(5.4)
(4.5)
(3.1)
(3.6)
(2.3)
(2.3)
(1.7)
(2.1)
(2.0)
(9.3)
(5.6)
(4.2)
(2.8)
(3.0)
(3.1)
(16)
(9)
HIIITHIS layer (raw humus)
36
(5.4)
? Figures in brackets are enrichment
ratios, calculated as the quotient between
the metal concentration of the component In
this site and of the same component In a
similar site with no local deposition.
-------
lOArr
ti\n\ I
DO fiOT QUOTE OR CITE
7.4 REFERENCES PO* SECT.ON 7
1. Tedeschi, R. E., and F. W. Sundennan. Nfckel Poisoning. V. The
Metabolism of Nickel under Normal Conditions and After. Exposure to
Nickel Carbonyl. A. M. A. Arch. Ind. Health. 1^:486-488, 1957.
2. Schroeder, H. A., J. J. Balassa, and I. H. Tipton. Abnormal Trace
Elements in Man-Nickel. J. Chron. Dis. j_5_:51-65, 1962.
3. Fisher, A, A, Contact Dermatitis. Philadelphia, Lea and Feh'ger,
1967. 324 p.
4. Hueper, W. C. Carbinogenic Hazards from Arsenic and Metal Containing
Drugs. In R. Truhart, Ed. Potential Carcinogenic Hazards
from Drugs. Evaluation of Risks» Berlin, Springer-Verlag, 1967.
pp. 79-104.
5. Schroeder, H..A. A Sensible Look at Air Pollution by Metals. Arch.
Environ. Health. 21_: 798-806, 1970.
6. Cogbill, E. C., and M. E. Hobbs. Transfer of Metallic Constituents
of Cigarettes to the Main Stream Smoke. Tobacco Sci. .. 1:68-73, 1957
7- Voss, R. C., and H. Nicol. 'Metallic Trace Elements in Tobacco.
Lancet.2:435-436, 1960.
8. Sunderman, F. W., and F. W. Sundermann, Jr. Nickel Poisoning. XI.
Implications of Nickel as a Pulmonary Carcinogen in Tobacco Smoke.
Amer. J. Clin. Pathol. 35_:203-209, 1961.
"9. Sunderman, F. W., and F. W. Sunderman, Jr. Nickel Poisoning.
XI Implication of Nickel on a Pulmonary Carcinogen in Tobacco
Smoke. Amer. J. Clin. Path. 35:203-209, 1961.
7-7
-------
uu
10.. Hueper, W. C. Carcinogenic Hazards from Arsenic and Metal Containing
Dru9s In: . Potential Carcinogenic
Hazards from Drugs. Evaluation of Risks. Truhart, P. (ed.). Berlin,
Springer-Verlag, 1967. p. 79-104.
11 f Whittmer, S. H.^and F. G. Tuebner. Foliar Absorption of Mineral
Nutrients. Ann. Rev. Plant Physiol. 5J3.-13-32. 1959.
12. Tyler, G- Moss Analysis - A Method for Surveying Heavy Metal
Deposition. In: Proceedings of the Second International Clean Air
Congress., Englund, H. M. and W. T. Beery (eds.), New York, Academic Press,
1971. p. 129-132.
13. Tyler, G. Heavy Metals Pollute Nature, May Reduce Productivity.
Ambio. 1:52-59, 1972.
7-*
-------
8. MECHANISMS OF RESPONSE fiPACT
8.1 ANIMAL METABOLISM QQ NOT QUOTE OR CITE
8.1.1 Transport
Ultrafilterable nickel complexes may function as carriers for the
2
extracellular transport and renal excretion of nickel. Estimates of
total serum nickel arid ultrafilterable fractions for several species are
shown in Table 8.1 .
Table 8.1. SERUM NICKEL IN SEVERAL SPECIES
Concentration, yg/100 ml
Specie Serum Ultrafilterable
Men 0.23 0.09
Dogs 0.23 0.20
Rabbits 0.90 0.14
Rats 0.66 0.18
Lobsters 0.88 , 0.33
Species differences in nickel-binding properties of serum albumin may
account for the variations in partitioning of serum nickel. Callan and
Sunderman reported the first association constants of serum albumin
for divalent nickel-63 as follows: man - 300,000; dog - 25,000;
rabbit - >300,000; rat - 200,000; and pig - 80,000 liters/mole.
"Nickeloplasmin" has been identified as an alpha-macroglobulin
3
which binds a portion of the nickel in normal serum of man and rabbits.
It is apparently a glycoprotein with esterase activity and a molecular
c
weight of 700,000. It resembles, but is not identical to the zinc-containing
S-'
-------
UKAh I
DO NOT QUOTE OR CITE
macroglobulin isolated from human serum.7 The nhysioloqic significance
of nickeloplasmln is not known.
8.1.'2< Excretion
Nickel that is ingested in food is for the most part unabsorbed and
excreted in the feces. The same holds true for soluble nickel in drinking
Q
water. In dogs, Tedeschi and Sunderman demonstrated that 90 percent ofJngested
nickel was recovered in feces and only 10 percent i'n urine
In rats fed nickel soaps or nickel catalyst of 250, 500 or 1000 yg/g
nickel in their diets, approximately 90 percent of the nickel was found in the
and
feces/ less than'l percent was excreted in the urine.9 When nickel was given as
nickel carbonate, 74 percent was excreted in the feces and 1.6 percent in
the urine. (Nickel tnat enters the body via the pulmonary route br by
parenteral administration is excreted predominately in the urine.
With injection of small doses of nickel-63 in the rat, 61 percent was excreted
in the urine and only 5.9 percent in the feces within 72 hours. Additional
studies on parenterally administered nickel will be discussed under Unde-
sirable Effects.
8.1.3 Binding tp_ Biological Substances
The biological activity of nickel depends upon the nature and location
of its intra- and extracellular binding sites. In general, nickel is
similar in binding properties to other metals of the first transition
series. It is unique in its divalent state, however,in that it exists in three
interconvertible geometric structures—square planar, octahedral, and
tetrahedral. Possible structure-function relationships have not been
routinely considered in studies on the biological activity of divalent
nickel.
-------
DRAFT
DO NOT QUOTE OR CITE
8.1.3.)> Binding to Nucleic Acids--Divalent nickel has been shown to bind
to phosphates, purines and pyrimi dines of DNA and RNA, providing conforma-
12 13
tional stabilization of the nucleic acids. ' Heating of RNA in the
presence of nickel results in breakage of phosphodiester linkages and
14-16- -
depolymerization. Binding of nickel to nucleic acids may have
adverse implications for the regulation of cell growth and division and
for the transfer of hereditary information.
8.1.3.2 Binding to Nucleotides--Divalent nickel binds to the separate
monomeric components of nucleic acids through the same functional groups
as in the polymerized forms. Adenosine triphosphate (ATP),which is required
in nucleic acid synthesis and in energy transfer for many biosynthetic
reactions, binds nickel as does the pyrmidine base of the coenzyme,thiamine
pyrophosphate.
8.1.3.3 Binding to Proteins—It has been determined that nickel binds to
17 18
carboxyl and imidazole groups of bovine and human serum albumin. The
19
alpha-ami no group of aspartic acid, a sulfhydryl group, and between the
20
terminal ami no group and the adjacent peptide have also been implicated
as nickel binding sites. The later mode of binding has been postulated
20 21
for vasopressin, alpha-chymotrypsin, ribonuclease, and myoglobin.
Divalent nickel binding has also been demonstrated with casein, gelatin,
pseudoglobulin, and keratin.
8.1.3.4 Binding to Peptides--The binding of nickel to oligopeptides has
served as a simplified model for the interaction of the metal with proteins.
Di- and triglycine form complexes with nickel with binding of the metal to
-------
DO NOT QUOTE OR
22
carboxyl, peptide nitrogen, and ami no groups. With triglycine,
22
chelation involves the peptide nitrogen and the ami no group. Peptides
with ami no acids containing sulfur or heterocyclic nitrogens also coordi-
23
nate with nickel through these electron donor atoms. Titration of
nickel-oligopeptide complexes can result in rearrangement of coordination
sites around nickel with concomitant conversion of the paramagnetic
octahedral complexes to diamagnetic square planar complexes. Whether these
transitions alter biological activity is not known. At least one case is known
in which the formation of a complex catalyses cleavage of a synthetic
octapep^ticK2
8.1.3.5 Binding to Ami no Acids--Amino acids that contain unique functional
groups, as for example, sulfhydryl groups or heterocyclic nitrogens,readily
form coordination complexes of these groups with nickel and the alpha-
25
ami no groups. Ami no acids that possess only carboxyl and alpha-ami no
groups chelate with nickel through these groups. Proline also forms such
complexes even though only one hydrogen is present on the available nitrogen
27
atom.
8.1.3.6 Other Divalent Nickel Complexes—Nickel has been shown to form
28 28 29
complexes with porphyrins, including uroporphyrins and bilirubin.
It has been postulated that nickel could thus interfere with biosynthesis
of porphyrin containing compounds such as hemoglobin and chlorophyll.
30
Nickel also binds to triphosphoinositide and phosphatidylserine as
well as to dihydro!ipoic acid. The later chelation could interfere with
31
the ultilization of pyruvate in the formation of coenzyme A. Divalent
32 33 3d
nickel binds to coenzyme A itself, to citric acid, and to phytic acid.
-------
DRAFT re
DO NOT QUOTE OR CITE
Whether the affinity of nickel for these or any of the substances
previously mentioned has significance in terms of mechanisms of physio-
logic effects, remains to be clarified.
8.1.4 Effects on Enzyme Activities
Nickel has not been shown to be an integral component of any enzyme
4 :
except nickeloplasminT but it does activate and/or inhibit certain enzyme
systems (Table 8.2). In interpreting enzyme activation and inhibition
data,-jt must be remembered that many factors influence enzyme deter-
minations such as enzyme and substrate concentrations, pH.and ionic strengths.
Experiments employing different assay conditions or enzymes of different
sources or purities are, therefore, not directly comparable.
Of the enzymes known to be inhibited by divalent nickel perhaps
58
5'-nucleotidase and adenosine triphosphatase are most important. The
former enzyme catalyzes the hydrolysis of the 5'-nucleotide phosphate. The later
catalyzes, the dephosphorylation of ATP, is extremely important in
energy transfer reactions.
s
8.1.5 Alterations in Nickel Metabolism in Disease
61-63
Ryabova has determined that artificially
induced myocardial ischemia produces a significant increase in myocardial
nickel concentration in dogs. However , there is no significant alteration
in mean serum nickel as is observed with myocardial infarction in man.
8.1.6 Effects p_n_ Excitable Tissues
In general, nickel competes with and imitates the effects of calcium
on excitable tissues-1nerves, myoneural junctions, and muscles. Nickel
the
binds to/reactive groups of proteins- such as the ammonium5
carboxyl, hydroxyl, and sulfhydryl, and to
-------
DO NOT QUOTE OR CITE
8.2. ACTIVATION AND INHIBITION OF ENZYME ACTIVITIES BY NICKEL
Enzyme Activation Inhibition
oxaloacetic decarboxylase
ribonuclease (bovine pancreas)
deoxyribonuclease I (pancreas)
carboxypeptidase
(for
arginase
enolase
phosphoglucomutase
ami no acid decarboxylase(s)
(from E.colt and C. w.elchii)
acetyl CoA synthetase
pyridoxal phosphokinase
thiaminokinase
pyruvic acid oxidase
salivary amylase (human)
citritase
ribulose diphosphate carboxylase
di al kyl f 1 uorophosphate
fluorohydrolase
aspartase
alkaline phosphatase(s)
5'-nucleotidase
(from bull seminal plasma)
adenosinp triohosohatase
Yes .. Yes
Yes • • Yes
yes
yes
the apoenzyme)
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes -
yes
yes
yes
yes yes
yes
ves
References
35
36
36
37,38
39,40
41,42
43,44,45
46
47
48
49
50
51
52
53
54,55
54,55 .
56,57,58
58
59,60
S-b
-------
DRAFT
00 NOT QUOTE OR CITE
proteins more strongly than does calcium. ' Nickel essentially causes
a prolonged action potential and uncoupling between membrane activation
and muscle contraction. Only the prolonged action potential occurs in
the presence of calcium, and this effect has a threshold nickel concentra-
tion of 0.00001 moles.
8.I.6.H. Excitable Membranes—Mechanistically^'nickel chloride .is thought to
prolong the nodal action potential by delaying and reducing inactivation of sodium
permeability and by delaying increase of potassium permeability. These
effects are explained by the assumption that divalent nickel and divalent calcium
ipete for the same membrane binding sites. Studies on this phenomenon have been
performed using the giant barnacle muscle, the vagus nerve of the cat,
large nonmyelinated axons of the lobster, and stretch receptors from cray-
fish. ' ' It is interesting to note that the action potential of the
giant squid axon is not affected by nickel.
Divalent nickel has also been shown to increase the threshold for
neural action-potential production. This increase in threshold by divalent nickel
antagonizes the effects of tetrodotoxin and procain.
8.1.6.2 Contractile Tissue—Divalent nickel increases the surface action
potential of skeletel muscle wrrr!' leads to a potentiation of the twitch
in both duration and amplitude and a .owering of the tetanus fusion
73 74
frequency. ' The observed increased duration of the active state is
believed to be related to these effects.
Divalent nickel also affects cardiac muscle by lengthening the Dlateau
phase of the ventricular action potential and reducing the contractile
forces of both atrium and ventricle. ' '
-------
DO MOT QUOTE OR CITE
With smooth muscle, application of millimolar quantities of nickel
results in a long lasting tonic response with inhibition of the phasic
response.
8^1-6.3 Neuromuscular Tran$nrission--Nickel has several effects at the
neuromuscular junction but none of them results in blocked transmission.
Prolongation of the axonal action potential by divalent nickel increases the
ion of the presynaptic potential which delays and prolongs the release of
79
transmitter. Divalent nickel also decreases the number of acetylcholine
"quanta" released by a single action potential probably by competing with divalent
calcium for the active site that controls quantal content and miniature
endplate potential frequency.
8.1.6.4 Central Nervous System--Few effects of nickel on the central
nervous system have been reported. Intravenous injection of high concentrations
of nickel chloride caused breakdown in the
• blood-brain barrier in rats. Epileptic seizures and death have been
82
produced by implantation of metallic nickel in the cerebral cortex.
8.1.7 Essentiality of_ Nickel
Criteria for essentiality as a micronutrient include: demonstra-
tion of the element in the fetus or newborn, presence of a homeostetic
mechanism regulating the metal's concentration, ' ' demonstration of a
metabolic pool of the element that is specifically altered by hormonal
fluctuations or pathologic states, presence of an enzyme in which the
element is an integral part,and demonstration of a deficiency state that
can be prevented or reversed by the element.
Nickel is situated in the periodic table among a number of essential
elements. A possible biochemical role for the metal is suggested by the
-------
DO NOT QUOTE OR CITE
fact that it readily undergoes transitions among several coordination
structures which may have different biological activities.
8.1.7.1 Presence of Nickel in the Fetus and Newborn—Schroeder and
coworkers 1iave shown that nickel is present in human fetal tissues.
Their conclusion that nickel can cross the human placenta was confirmed
83
by McNeely et ale with the finding that the mean concentration of nickel
in cord serum from 12 newborn human infants (0.30 +^ 0.12 yg/iOO ml; range, 0.13
too -49 yg/lOOnVl It should be noted that the presence of nickel in the
fetus or newborn does not necessarily indicate essentiality but may
simply reflect maternal contamination.
84
8.1.7.2 Homeostas_i_s_ of Nickel--Mertz and associates demonstrated in 1970
that the human kidney possesses an active excretory mechanism for nickel.
85
Also, Nielsen and Sauberlich demonstrated concentration of radiolabeled
nickel in liver, spleen and aorta by chicks on a nickel deficient diet
as compared to controls on the same diet supplemented with nickel. Thus,
mechanisms apparently exist to explain the fact that serum nickel is
3
normally maintained within narrow and characteristic concentration ranges.
8.1.7.3 Metabolic Pools of Nickel--Metabolic pools of nickel do not appear
to be altered by endocrine factors or hormonal substances. For example,
there are no differences in serum nickel concentrations between males
and females of any species studied, and maternal serum levels do not change
83 86
upon giving birth. ' However, changes in metabolic pools of nickel do
occur in certain disease states. Serum nickel concentrations are signi-
ficantly increased following myocardial infarctions and after stroke and
QO 07 op QQ
burns. ' ' They are decreased in hepatic cirrosis and chronic uremia.
also 89
Hepatic nickel levels are/increased in hepatic cirrosis.
-------
DRAFT „
DO NOT QUOTE OR CITE
8-1'7?4 A Nickel-Containing Meta11op.rj3.tein—As previously mentioned,
human and rabbit serum has been demonstrated to contain a nickel metallo-
protein that appears free of other metals. ' ' This alpha-macro-
globulin possesses protein esterase activity, as is characteristic of this
group of globulins, and, therefore, conforms to the essentiality criterion
as a metalloenzyme.
90 91
8.1,f7.5 Nickel Deficiency in Experimental Animals—Nielsen and coworkers '
V
have shown that nickel deprived chicks (40to 80 ppb in diet) have swollen hock
joints, reduced length: width rations' of the tibias, yellow-orange discoloration
with scaly dermatitis of the legs and fat depleted livers. Others have
not observed such a syndrome and subsequently Nielsen and Ollerich were
91 92 93
not able to repeat their original work. However, Sunderman e_t al_
did observe decreases in mean serum and hepatic nickel levels in chicks
on a 44 ppb nickel diet. Sunderman ejt al_. also reported perimitochondrial
dilatation of rough endoplasmic reticulum in nickel deprived chicks which
according to Piccardo and Schwarz may be the earliest ultrastructural lesion
in hepatocyte degeneration. This finding was confirmed by Nielsen and
92
Ollerich and thus indicates the probable dietary essentiality of nickel.
-S-ID
-------
DRAFT „
DO MOT QUOTE OR CITE
8,2 HUMAN MECHANISMS OF RESPONSE
8.2.1 Uptake
Though the usual oral intake of nickel by American adults is estimated
to be 300 to 600 yg/day, most of this remains unabsorbed within the gastro-
95
intestinal tract. Schroeder and associates suggested that there is a
mechanism which limits absorption of nickel in'/mammals, despite the
relatively large amount of nickel present in food. If such a mechanism
exists, it adds credence to the possibility that nickel may be an essential
trace element in human metabolism.
Nickel may be inhaled into the respiratory tract both from the
atmosphere and from tobacco smoke. An adult resident of New.
York City could have inhaled as much as 2.36 yg of nickel a day fl966),
and a resident of East Chicago, Illinois, could have inhaled a maximum
of 13.8 iag of nickel per day (1964). Sunderman made similar estimates
for nickel inhalation from smoking: a maximun of 14.8 yg of nickel per
97
day for a two-package a day smoker.
Percutaneous absorption and parenteral administration are negligible means
of nickel uptake but are clini.-'ily significant because of the
development of hypersensitivity.
8.2.2 Distribution and Excretion ,
There are approximately 10 yg of nickel in a normal man, but wide variations
98
exist. Tipton et. al. studied autopsy tissues from 173 subjects,
apparently healthy Americans who had died suddenly and had no visible
-------
U1W I
DO NOT QUOTE OR CiTE
disease condition at the time of death. There was a significantly higher
nickel concentration among males. Nickel was observed in only about one-
third of all samples analyzed (29 tissues per subject), although it was
observed in every tissue. The greatest frequency and the highest concen-
x1... ..^ .- ,. •
tratibn occurred in skin. The lung, omentum, and intestinal caecum had the '
highest median values for nickel content among the tissues examined. As
to frequency in occurrence of nickel among the tissue samples, the following
•
percentages describe the distribution: lung, 65Lpercent; aorta, 49 percent;
trachea, 49 percent; heart, 42 percent: Ridney 38 percent; larynx, 31 percent;
' . . . QC,
liver, 25 percent; and 87 percent of intestine and skin samples.
100
McNeely and associates have shown that measurements of nickel in serum ancj
urine can serve as biological indices Of environmental exposure to nickel.
This study compared serum and urine nickel levels from healthy hospital
employees in Sudbury, Ontario and in Hartford, Connecticut. For the
Sudbury subjects, the mean serum nickel concentration was 4.6 i-1.4 yg/liter
(n=25) and their average urinary nickel excretion was 7.9 -3.7 yg/day .
(n=19). For the Hartford subjects, the mean serum: nickel concentration
was 2.6 - 1.0 yg/liter (n=26), and their average urinary nickel excretion
was 2.5 - 1.4 yg/day (n=20).
The major route of elimination of nickel from the human body is that
of fecal excretion. In a study of ten healthy hospital employees in
Hartford, Connecticut, the fecal excretion of nickel averaged 258 yg/day
(SD, 1126). This was approximately 100 times greater than the mean daily
excretion of nickel in urine.
Nickel is also excreted from the body in sweat. The mean concentration
of nickel in arm sweat from 33 healthy men exposed to dry heat of a sauna
bath was 52 - 36 yg/liter.102
-------
DRAFT
00 NOT QUOTE OR CITE
Measurement by atomic absorption spectrometry of the nickel content
of human hair specimens indicated
a mean concentration of 0.1 -0.08 yg/g (n=20). There was no
significant difference observed in mean nickel concentration between men
and women; however, there was a significant diminution in nickel concentra-
tion with advancing age. Elimination of nickel in desquamated hair
is one of the physiologic routes for the excretion of nickel from the body.
8.2.3 Metabolism
Studies have shown that nickel is maintained within a characteristic
range of concentrations in the blood serum of man: mean, 2.6 pg/ liter;
range, 1.1-4.6 yg/liter; standard deviation, -0.8; and n=47. Patho-
logical alterations of serum nickel concentrations have been found to
occur in various common diseases of man—with an elevated serum nickel
occurring following myocardial infarction, stroke, and severe burns; and
a lowering of serum nickel occurring in patients with hepatic cirrhosis,
u .105
or chronic uremia.
The occurrence of nickeloplasmin, a nickel-containing
matalloprotein in serum, suggests that nickel, like other metals in the
first transition of the periodic table, may play an essential physiologic
role.104
The biologic effects of nickel depend upon the nickel binding sites
within the human cell. Nickel binding to biologically important sources
are generally like the effects of other metal ions, particularly ions of the
-------
DRAFT
DO NOT QUOTE OR CITE
first transition series, to which nickel belongs. Nickel and other
metal ions exert profound effects on genetic material. It has been
demonstrated that divalent nickel binds to both the phosphates and
Of in?
heterocyclic bases/DNA arid RNA. '
The biological synthesis and degradation of nucleic acids involve
the-nucleotides, which bind primarily through the phosphate groups, but
also by base binding. This binding occurs with adenosine triphosphate
(ATP), an important cellular constituent involved in energy transfer
and many enzymatic reactions.
-------
DRAFT
DO NOT QUOTE OR CITE
8.3 PLANTS
Plants exhibit a wide variation in their response to nickel concen-
trations in the soil. Plant response is associated with their tolerance
to metals. The factors which determine the response are not well known. Few
gymnosperms grow in soils with high concentrations of nickel. The
108
majority of the flora, found on serpentine soils are perennial herbs.
It has been noted that the chromosome numbers of these plants differ
from those of plants growing on non-serpentine soils.
Tolerance mechanisms in plants may be "external" or "internal".
External mechanisms prevent the
entrance of metal ions. The circumstances which prevent entry are not
strictly plant controlled, but still are important in deter-
'108
mining plant response. Antonovics ~et al. have outlined
both the "external" and "internal"mechanisms ( Table 8.3). Basically,
these mechanisms are the same for the majority of heavy metals.
Some of the plants growing in soils with high concentrations of
nickel have developed a mechanism which prevents the metal from reaching
the sites of active metabolism by chelation in the cell wall. Alyssum
bertoloni, which accumulates nickel and grows on serpentine soils, con-
centrates the nickel in the epidemis arid sclerenchymatous areas (non-
living cells which provide the plant with support). Nickel is also
accumulated in the leaves of Hybanthus f1oribundus. It has been suggested
that this accumulation of nickel is an adaptation by the plant to the
109
xeric conditions under which it grows.
-------
8.3. POSSIBLE MECHANISMS OF METAL TOLERANCE IN
DRAFT
QUOTE OR Cllt
A. External
Form of metal is not directly sol-
uble in water and/or if dissolved
then rapidly diluted by surround*
ing water.
A«tiial amount of freely diffumbto
motel tens it mnall compared to
total amount present.
Lack of permeability to heavy
metals under specific conditions.
i Metal Ion antagonism*,
• i
'•!
B. Internal
Differential uptake of ions.
Ronwtal of metal ions from
metabolism by deposition in
vacuole.
Removal of metal ions from
metabolism by pumping from
cell.
Removal of motal ions from
metabolism by rendering into an
innocuous form.
Excretory mochnn isms — re-
moval of "metal sfcorapo organ".
Greater requirement of enzyme
systems for motal ions.
Alternative metabolic pathway
by-passing inhibited site.
Increased concentration of
metabolite that antagonizes in-
hibitor.
Increased concentration of en-
r,ymo that is inhibited.
Decreased requirement for pro-
ducts of inhibited system.
Formation of altered enzyme
with decreased affinity for in-
hibitor or increased relative
affinity for mtbfltrato compared
to the competitive inhibitor.
Decreased permeability of coll
or subosllular units to metal
tons.
Alteration 'in protoplasm so that
MnytneB may function even
when tojtte metals replace physl-
ologioal metals.
-------
DRAFT
DO NOT QUOTE OR CITE
Tolerant plants have been found to be metabolically different
108
from normal plants at low metal levels.
Plants which cannot tolerate high concentrations of nickel, do
not grow on nickeliferous soils.
Iron and sulfur oxidizing bacteria are capable of using metal
108 112
sulfide minerals as energy sources. For example, Thiobacillus ferroxidans
converts millerite (NiS) to divalent nickel^sjilfhydryl, anH suifate ions through
an oxidation process.
This results in the solublization of the nickel sulfide ore and the
production of sulfuric acid. ' Because of the production of sul-
furic acid, the medium surrounding this process becomes highly acidic--pH
1 to 2. These reactions are typical of mine drainage areas.
8-17
-------
DRAFT
DO NOT QUOTE OR CITE
3.4 REFERENCES
1. Callan, W. M.. and F. W. Sunderman, Jr. Species Variations
63
in Binding of Ni(II) by Serum Albumin. Res. Commun. Chem.
Path. Pharmacol._5_: 459-472, 1973.
63
2. Van Soestbergen, M.,and F. W. Sunderman, Jr. Ni Complexes
in Rabbit Serum and Urine After Injection of 63NiCl2. Clin.
Chem. J8_: 1478-1484, 1972.
3. Nomoto, S., M. D. McNeely, and F. W. Sunderman, Jr. Isolation
of a Nickel a2-macroglobulin from Rabbit Serum. Biochem.
10: 1647-1651, 1971.
4. Himmelhoch, S. R., H. A. Sober, B. L. Vallee, E. A. Peterson,
and K. Fuwa. Spectrographic and Chromatographic Resolution
of Metalloproteins in Human Serum. Biochenu _5_i 2523-2530,
1966.
5. Sunderman, F. W., Jr., M. I. Decsy, and M. D. McNeely. Nickel
Metabolism in Health and Disease. Ann. N. Y. Acad. Sci. 199:
300-312, 1972.
CO
6. Decsy, M. I.,and F. W. Sunderman, Jr. Binding of Ni to Rabbit
Serum a,-macroglobulin in vivo and in vitro. Bioinorgan . Chem.
(In Press).
7. Parisi, A. F., and B. L. Vallee. Isolation of a Zinc ap-macro-
globulin from Human Serum. Biochem, jh 2421-2426, 1970.
8. Elakhovskaya, N. P. Metabolism of Nickel Entering the Body with
Drinking Water. Gig. Sanit._37: 20-22, 1972. (In Russian).
9. Nalimova, L. S. The Metabolism of Cobalt and Nickel in Children
with Leukemia {Materialy 1-go (Pervpgo) S'ezda Detsk. Vrachei
Belorussii Minsk.] Sb. 160-161, 1964. (In Russian).
£-1*
-------
DRAFT
DO NOT QUOTE OR CITE
10. Phatak, S. S., and V. N. Patwardhan. Toxicity of Nickel. J. Sc1..
Ind. Res. 9b_(3): 70-76, 1950.
11. Smith, J. C.,and B. Hackley. Distribution and Excretion of
Nickel-63 Administered Intravenously to Rats. J. Nutr. 95:
541-546, 1968.
12. Eichhorn, G. L,, and Y. A. Shin. Interaction of Metal Ions with
Polynucleotides and Related Compounds. XII. The Relative Effect
of Various Metal Ions on DNA Helicity. J. Amer. Chem. Soc.
90: 7323-7328, 1968.
13. Shin, Y. A., J. M. Heim and G. L. Eichhorn. Interaction of Metal
Ions with Polynucleotides and Related Compounds. XX. Control of
the Conformation of Polyriboadenylic Acid by Divalent Metal Ions.
Bioinorgan. Chem.Jj 149-163, 1972.
14. Butzow, J. J.,and G. L. Eichhorn. Interactions of Metal Ions with
Polynucleotides and Related Compounds. IV. Degradation of Poly-
ribonucleotides by Zinc and Other Divalent Metal Ions. Biopolymers.
_3: 95-107, 1965.
15. Hueper, W. C. Carcinogenic Hazards from Arsenic and Metal Con-
taining Drugs. 'In: Potential Carcinogenic Hazards from Drugs.
Evaluation of Risks. Truhaut, R. (ed.). Berlin; Sprinaer-Verlag,
1967. p. 79-104.
16. Matsushita, S., and F. Ibuki. Hydrolysis of Ribonucleic Acid by
Metal-Ion-catalyzed Reaction. I. Mode of Reaction. Mem. Res.
Inst. Food Sci., Kyoto University No. 22: 32-37, 1960.
-------
17. Rao, M. S. N.,and H
DRAFT •
DO NOT QUOTE OR CITE
. Lai. Metal Protein Interactions in Buffer
Solutions. Part II. A Polarographic Study of the Interaction
of Zn and Cd with Bovine Serum Albumin. J. Amer. Chem. Soi.
80: 3222-3226, 1958.
18. Rao, M. S. N. A Study of the Interaction of Nickel (II) with
Bovine Serum Albumin. J.. Amer. Chem. Soc. 84; 1788-1790, 1962.
19. Peters, T., Jr., and F. A. Blumenstock. Copper-binding Properties
of Bovine Serum Albumin and Its Ami no-terminal Peptide Fragment.
J. Biol. Chem._242_: 1574-1578, 1967.
20. Tsangaris, J. M., J. W. Chang,and R. B. Martin. Cupric and
Nickel Ion Interactions with Proteins as Studied by Circular
Dichroism. Arch. Biochem. Biophys. 130; 53-58, 1968.
21. Bryce, G. F., R. W. Roeske*and F. R. N. Gurd. L-Histidine-
containing Peptides as Models for the Interaction of Copper(II)
and Nickel (II) Ions with Sperm Whale Apomyoglobin. J. Biol.
Chem. 241_: 1072-1080, 1966.
22. Freeman, H. C., J. M. Guss >and R. L. Sinclair. Crystal Structures
of Four Nickel Complexes of Glycine and Glycine Peptides. Chem.
Comm. No. 1-12: 485-487, 1968.
23. Chang, J. W, and R. B. Martin. Visible Circular Dichroism of
Planar Nickel Ion Complexes of Peptides and Cysteine and Derivatives.
J. Phys. Chem._73_: 4277-4283, 1969.
24. Boldt, J. R., Jr. The Winning of Nickel. Its Geology, Mining
and Extractive Metallurgy. New York, D. Van Nostrand Company, Inc.,
1967. 487 p.
-------
DRAFT .
00 NOT QUOTE OR CITE
25. Lenz, C. R. and A. E. Martell. Metal Complexes of Carnosine.
Biochem. ^_3j 750-753, 1964.
26. Hatem, S. [ Complexion de 1'histamine par le nickel, le cobalt,
le chrome et le glucinium.] Chimia 1£: 130-133, 1960.
27. Herlinger, A. W.,and T. V. Long, II. Laser-Raman and Infrared
Spectra of Ami no Acids and Their Metal Complexes. III. Proline
and Bisprolinato Complexes. J. Amer. Chen. Soc._92: 6481-6486, 1970.
28. Falk, J. E. Porphyrins and Metal!oporphyrins. Their General,
Physical and Coordination Chemistry, and Laboratory Methods.
Amsterdam, Elsevier Publishing Co., 1964. 266 p.
29. Velapoldi, R. A., and 0. Menis. Formation and Stabilities of
Free Bilirubin and Bilirubin Complexes with Transition and
Rare-earth Elements. Clin. Chem. l_7j 1165-1170, 1971.
30. Hendrickson, H. S., and J. G. Fullington. Stabilities of Metal
Complexes of Phospholipids: Ca(II), Mg(II), and Ni(ll) Complexes
of Phosphatidylserine and Triphosphoinositide. Biochem • _4^
1599-1605, 1965.
31. Webb, M. The Biological Action of Cobalt and Other Metals. III.
Chelation of Cations by Dihydroliopic Acid. Biochim. Biophys.
Acta 65: 47-65, 1962.
32. Stern, J. R. Optical Properties of Acetoacetyl-S-Coenzyme A and
Its Metal Chelates. J. Bibl. Chem._221: 33-44, 1956.
33. Hietner, W. C., D. Friedman, J. M. E. Goldschmidt, and
J. Shamir. [Contribution a 1'etude des complexes des citrates et
tartrates. 3. Le complexe du nickel avec le citrate. ] Eull.
Soc. Chim. France 76:864-867, 1958.
-------
DRAFT
DO NOT QUOTE OR CITE
34. Vohra, P., G. A. Gray^and F. H. Kratzer. Phytic Acid-metal
Complexes. Proc. Soc. Exp. Biol. Med. 120: 447-449, 1965.
35. Speck, J. F. The Effect of Cations on the Decarboxylation of
Oxalacetic Acid. J. Biol. Chem. 178: 315-324, 1949.
36. Eichhorn, G. L., P. Clark, and E. Tarien. The Interaction of
Metal Ions with Polynucleotides and Related Compounds. XIII.
The Effect of Metal Ions on the Enzymatic Degradation of Ribo-
nucleic Acid by Bovine Pancreatic Ribonuclease and of Deoxyribonucleic
Acid by Bovine Pancreatic Deoxyribonuclease. I. J. Biolog. Chem.
.244: 937-942, 1969.
37. Coleman, J. E.,and B. L. Vallee. Metallocarboxypeptidases:
Stability Constants and Enzymatic Characteristics. J. Biolog*
Chem. _236: 2244-2249, 1961.
38. Vallee, B. L., J. A. Rupley, T. L. Coombs, and H. Neurath. The
Role of Zinc in Carboxypeptidase. J. Biol. Chem. 235: 64-69, 1960.
39. Hellerman, L.,and M. E. Perkins. Activation of Enzymes. III.
The Role of Metal Ions in the Activation of Arginase. The Hydrolysis
of Arginine Induced by Certain Metal Ions with Urease. J. Biol.
Chem. JJ2_£l75-194, 1935.
40. Greenberg, D. M., A. E. Bagot.and 0. A. Roholt, Jr. Liver
Arginase. III. Properties of Highly Purified Arginase. Arch.
Biochem. Biophys. 62; 446-453, 1956.
41. Malmstrom, B. G. Metal-ion Specificity in th.e Activation of
Enolase. Arch. Biochem. Biophys. 58: 381-397, 1955.
42. Malmstrom, B. G. The Interaction of Dl-2-phosphoglyceric Acid
with Metal Ions Activating Enolase. Arch. Biochem. Biophys. 49:
335-342, 1954.
-------
DRAFT
DO NOT QUOTE OR CITE
43. Palmer, J. D. Sulphate of Nickel in Neuralgia. Richmond
Louisville Med. J 5: 270-271, 1868.
44. Peck, E. J., Jr.,and W. J. Ray, Jr. Role of Bivalent Cations
in the Phosphoglucomutase System. III. Structure-function
Relationships in the Ternary Enzyme-metal-substrate Complex.
J. Biol. Chem. 244:3754-3759, 1969.
45. Ray, W. J., Jr. Role of Bivalent Cations in the Phosphoglucomutase
System. I. Characterization of Enzyme-metal Complexes. J. Biol.
Chem. 244: 3740-3747, 1969.
46. Eggleston, L. V. Effects of Cations on Amino Acid Decarboxylases.
Biochem. J. _68: 557-560, 1958.
47. Webster, L. T., Jr. Studies of the Acetyl Coenzyme A Synthetase
Reaction. III. 'Evidence of a Double Requirement for Divalent
Cations. J. Biol. Chem._240: 4164-4170, 1965.
48. Hurwitz, J. The Enzymatic Phosphorylation of Pyridoxal. J.
Biol. Chem. 205: 935-947, 1953.
49. Mano, Y. and R. Tanaka. Studies on Enzymatic Synthesis of Cocar-
boxylase in Animal Tissue. IV. Effect of Metallic Ions, Various
Nucleotides and Thiamine Derivatives on Thiaminokinase from Rat
Liver. J. Biochem. 4J7: 401-413, :960.
50. Stumpf, P. K. Pyruvic Oxidase of Proteus Vulgaris. J. Biol.
Chem. 159: 529-544, 1945.
51. Urata, G. The Influence of Inorganic Ions on the Activity of
Amylases. J. Biochem. 44: 359-374, 1957.
52. Dagley, S.,and E. A. Dawes. Citridesmolase: Its Properties
and Mode of Action. Biochim. Biophys. Acta.J^ 177-184, 1955.
-------
DRAFT
, 00 NOT QUOTE OR CITE
i
53. Weissbach, A., B. L. Horecker.and J. Hurwitz. The Enzymatic
Formation of Phosphoglyceric Acid from Ribulose Disphosphate
and Carbon Dioxide. J. Biol. Chem. 218: 795-810, 1956.
54. Ellfolk, N. Studies on Aspartase. V. Inactivation and Re-
activation of Aspartase. Acta. Chem. Scand._9: 771-780, 1955.
55. Mounter, L. A.,and A. Chanutin. Dialkylfluorophosphatase of
Kidney. II. Studies of Activation and Inhibition by Metals.
J. Biol. Chem. 204: 837-846, 1953.
56. Freiman, D. G. Metal Activation of Alkaline Phosphatase and
5-nucleotidase. Histochemical Studies. Lab. Invest. 5: 338-
347, 1956.
57. Freiman, D. 6. Use of an Organic Chelating Agent in Histochemical
Study of Alkaline Phosphatase Activation. Proc. Soc. Exp. Biol.
Med. 84^ 338-341, 1953.
58. Schwartz, M. K.,and 0. Bodansky. Properties of Activity of 5'-nucle-
otidase in Human Serum, and Applications in Diagnosis. Amer.
J. Clin. Pathol42: 572-580, 1964.
59. Kaye, M. A. G. The Effect of Zinc on 5-nucleotidase of Cobra
Venom and the Interference of Other Nucleotides. Biochim.
Biophys. Acta J8: 456-458, 1955.
60. Raff, E. C.,and. J. J. Blum. Some Properties of a Model Assay
for Ciliary Contract!bility. J. Cell. Biol. 42: 831-834, 1969.
61. Ryabova, V. V. Levels of Some Trace Elements in the Blood of
Dogs During Experimental Acute Myocardial Ischemia. Tr. Voronezh.
Gos. Med. Inst. 58: 90-93, 1967 (In Russian).
-------
DRAFT
00 NOT QUOTE OR CITE
62. Ryabova, V. V. Trace Element Levels in Some Dog Organs During
Acute Experimental Myocardial Ischemia. Vop. Biol. Med. Khim.
Mater. Nauch. Biokhim. Konf._I^ 52-54, 1968. (In Russian).
63. Ryabova, V. V. Trace Elements in the Cardiac Muscle During
Experimental Acute Myocardial Ischemia. Tr. Voronezh. Gos. Med.
Inst. 58: 94-97, 1967. (In Russian).
64. Gurd, F. R. N.*and P. E. Wilcox. Complex Formation Between
Metallic Cations and Proteins, Peptides, and Amino Acids.
Adv. Protein Chem. V\j_ 311-427, 1956.
65. Hagiwara, S.,and K. Takashashi. Surface Density of Calcium
Ions and Calcium Spikes in the Barnacle Muscle Fiber Membrane.
J. Gen. Physiol.JjQ: 583-601, 1967.
66. Meves, H. Die Wirkung von NiClp auf den isolierten Ranvierschen
Schnurring.[]Pfluegers Arch. 278: 273-295, 1963.
67. Amor, A. J. The Toxicology of the Carbonyls. J. Ind. Hyg. 14_^
217-221, 1932.
68. Blaustein, M. P., and D. E. Goldman. The Action of Certain Poly-
valent Cations on the Voltage-Clamped Lobster Axon. J. Gen.
Physiol._5J: 279-291, 1968.
69. Washizu, Y. Grouped Discharges c.f the Crayfish Stretch Receptor
Neuron Under Intracellular Injections of Drugs and Ions. Comp.
Biochem. Physiol.JH: 535-545, 1965.
70. Spyropoulos, C. S., and R. 0. Brady. Prolongation of Response
of Node of Ranvier by Metal Ions. Science. 129: 1366-1367, 1959.
-------
DRAFT
DO NOT QUOTE OR CITE
71. Khodorov, B. I. and V. I. Belyayev. Changes in the Critical
Level of Depolarization and the Action Potentials of a Single
Node of Ranvier with Electrotonus on Exposure to Cadmium and
Nickel Ions. Biophys . _8j 765-775, 1963.
72. Khodorov, B. I.^and V. I. Belyayev. Effect of Membrane Hyper-
polarization and of Calcium and Nickel Ions on Electrical
Activity of the Single Node of Ranvier on Exposure to Tetro-
dotoxin and Procaine. Biophys . 12: 981-992, 1967.
73. Fischman, D., and R. C. Swan. Nickel Substitution for Calcium
in Excitationcontraction Coupling of Skeletal Muscle. J. Gen.
Physiol._50: 1709-1728, 1967.
74. Sandow, A., and A. Isaacson. Topochemical Factors in Potentiation
of Contraction by Heavy Metal Cations. J. Gen. Physiol.^9_:
937-961, 1966.
++
75. Kaufmann, R.} and A. Fleckenstein. Ca -kompetitive elektro-
mechanische Entkoppelung durch Ni und Co -lonen am Warmblu-
termyokard.[] Pfluegers Arch._282: 290-297, 1965.
76. Kleinfeld, M.^and E. Stein. Action of Divalent Cations on Membrane
Potentials and Contractility in Rat Atrium. Amer. J. Physio!.
215: 593-599, 1968.
77. Kleinfeld, M., E. Stein,and D. Aguillardo. Divalent Cations on
Action Potentials of Dog Heart. Amer. J. Physio!. 211: 1438-1442,
1966.
78. Imai, S., and K. Takeda. Actions of Calcium and Certain Multivalent
Cations on Potassium Contracture of Guinea-pigs Taenia cdli.
J. Physiol.J90: 155-169, 1967.
-------
DRAFT
DO NOT QUOTE OR CITE
79. Benoit, P. R, and J. Mambrini. Modification of Transmitter
Release by Ions Which Prolong the Presynaptic Action Potential.
J. Physiol. 20: 681-695, 1970.
80. Mambrini, J.;and P. R. Benoit. Action du Nickel sur la Liberation
du Transmetteur a la Junction Neuromusculaire. C. R. Soc. Biol.
(Paris)_J61_: 524-528, 1967.
81. Varkonyi, T.,and F. Joo. The Effect of Nickel Chloride on the
Permeability of the Blood-brain Barrier. Experientia 24: 452-
453, 1968.
82. Chusid, J. G.»and L. M. Kopeloff. Epileptogenic Effects of Pure
Metals Implanted in Motor Cortex of Monkeys. J. Appl. Physiol.
V7: 697-700, 1962.
83. McNeely, M. D., F. W. Sunderman, Jr., M. W. Nechay, and H. Levi.ne. .
Abnormal Concentrations of Nickel in Serum in Cases of Myocardial
Infarction, Stroke, Burns, Hepatic Cirrhosis, and Uremia. Clin.
Chem. 17: 1123-1128, 1971.
84. Mertz, D. P., R. Koschnick, and G. W1lk. Renale Ausscheidungs-
bedingungen von Nickel beim Menschen.[]Z. Klin. Chem. Klin.
Biochem._8^ 387-390, 1970.
85. Nielsen, F. H.,and H. E. Sauberlich. Evidence fora Possible
Requirement for Nickel by the Chick. Proc. Soc. Exp. Biol. Med.
J34.: 845-849, 1970.
86. Nomoto, S., M. I. Decsy, J. R. Murphy, and F. W. Sunderman, Jr.
CO
Isolation of Ni-labelled Nickeloplasmins from Rabbit Serum.
Biochem. Med. 8: 171-181, 1973.
, —>
-------
DRAFT
00 NOT QUOTE OR CITE
87. Alonzo, C. A..and S. Pell. A Study of Trace Metals in Myocardial
Infarction. Arch. Environ. Health 6_: 381-385, 1963.
88. Sunderman, F. W., Jr., S. Nomoto, A. M. Pradhan, H. Levine,
S. H. Bernstein, and R. Hirsch. Increased Concentrations of Serum
Nickel After Acute Myocardial Infarction. New England. J. M.ed.
283: 896-899, 1970,
89. Volini, F., 0. de la Huerga,and G. Kent. Trace Metal Studies in
Liver Disease Using Atomic Absorption Spectrometry. In: Laboratory Diagnosis
of Liver Diseases. Sunderman, F. W., and F. W. Sunderman, Jr.. (Eds.).
St. Louis, Warren II. Green, Inc., 1968.
90. Nielsen, F. H.,and D. J. Higgs. Further Studies Involving a Nickel
Deficiency in Chicks. , In: Trace
Substances in Environmental Health. Proceedings of the University .
of Missouri's Fourth Annual Conference on Trace Substances in
Environmental Health. Vol. 4. Columbia, University of Missouri
Press, 1971. p. 241-246.
91. Smith, J. C., Jr. A Controlled Environment System for Trace Element
Deficiency Studies. In: Trace
Substances in Environmental Health. Proceedings of the University
of Missouri's Second Annual Conference on Trace Substances in
Environmental Health. Vol. 2. He'mphill, D. C. (Ed.). Columbia,!'
University of Missouri Press, 1969. p. 223-242.
92. Nielsen, F. H.,and D. A. Ollerich. Nickel: A New Essential Trace
Element. Fed. Proc. (In Press).
93. Sunderman, F. W., Jr., S. Nomoto, R. Morang, M. W. Mechay,
C. N. Burke, and S. W. Nielsen. Nickel Deprivation in Chicks.
J. Nutr. 102: 259-267, 1972.
-------
DRAFT
DO NOT QUOTE OR CITt
94. Piccardo, M. G. and K. Schwarz. The Electron Microscopy of
Dietary Necrotic Liver Degeneration. in:
Liver Function. A Symposim on Approaches to the
Quantitative Description of Liver Function. Publ. No. 4. Brauer, R.D. (Ed.),
Washington, D. C. American Institute of Biological Sciences,
1958. p. 528-534.
95. Schroeder, H. A., J. J. Balassa, and I. H. Tipton. Abnormal
Trace Elements in Man—Nickel. J. Chron. Dis. 15:15-65, 1962.
15-65, 1962.
96. Schroeder, H. A. A Sensible Look at Air Pollution by Metals.
Arch. ' Environ. Health.^]: 798-806, 1970.
97. Sunderman, F. W. and F. W. Sunderman, Jr. Nickel Poisoning.
XI. Implications of Nickel as a Pulmonary Carcinogen in Tobacco
Smoke. Amer. J. Clin. Pathol. "~ 35; 203-209,
1961.
98. Tipton, I. H., M. J. Cook, R. L. Steiner, C. A. Boye, H. M. Perry, Jr.,
and H. A. Schroeder. Trace Elements in Human Tissue. Part I -
Methods. Health Physics^ 89-101, 1963.
99. Tipton, I. H., and M. J. Cook. Trace Elements in Human Tissue.
Part II - Adult Subjects from the United States. Health Physics
_9j 103-145, 1963.
100. McNeely, M. D., M. W. Nechay, and F. W. Sunderman, Jr. Measurements
of Nickel in Serum and Urine as Indices of Environmental Exposure
to Nickel. Clirv Chenv. 18; 992-995. 1972.
101. Horah, E., and F. W. Sunderman, Jr. Fecal Nickel Excretion by
Healthy Adults. Clin.. Chew 19: 429-430. 1973.
-------
DRAFT
00 NOT QUOTE OR CITE
102. Hohnadel, D. C., F. W. Sunderman, Jr., M. W. Nechay, and
M. D. McNeely. Atomic Absorption Spectrometry of Nickel, Copper,.
Zinc, and Lead in Sweat Collected from Healthy Subjects During
Sauna Bathing. Clin. Chem. 19; 1288-1292, 1973.
103. Nechay, M. W.,and F. W. Sunderman, Jr. Measurement of Nickel
in Hair by Atomic Absorption Spectrometry. "Ann". Clin.
Lab. Sci. _3: 30-35, 1973.
104. Sunderman, F. W., Jr., M. I. Decsy, and M. W. McNeely. Nickel
Metabolism in Health and Disease. "AnnI N. Y. Acad. '
Sci. 199: 300-312, 1972.
105. McNeely, M. D., F. W. Sunderman, Jr., M. W. Nechay, and H. Levine.
Abnormal Concentrations of Nickel in Serum in Cases of Myocardian
Infarction, Stroke, Burns, Hepatic Cirrhosis, and Uremia. Clin.
Chem. 17: 1123-1128, 1971.
... Nickel..
106./ Final report to U. S. Environmental Protection Agency, Research Triangle
Park, N. C. on Contract No. 68-02-0542 from the National Academy of
Sciences, Washington, D. C. 1974. p. 125-126.
107. Eichhorn, G. L.^and Y. A. Schin. Interaction of Metal Ions with
Polynucleotides and Related Compounds XII. The Relative Effect
of Various Metal Ions on DNA Helicity. J. Amer.
Chem. Soc. . 90: 7323-7328. 1968.
108. Antonovics, J., A. D. Bradshaw, and R. G. Turner. Advance? in
London,
Ecological Research. Vol. 7./ Academic Press. 1971. P- 2-85.
109. Severne, B. C. Nickel Accumulation by Hybanthus floribundus.
Nature.248: 807-808, 1974.
-------
DRAFT
00 NOT QUOTE OR CITE
110. Zajic, J. E. Microbial Biogeochemistry. New York, Academic Press,
1969. p. 345.
111. Lundgren, D. D., J. A. Vental,and F. R. Tabita. The Microbiology
of Mine Drainage Pollution- . , In: , Water Pollution Micro-
biology . Mitcfiell, R. (ed.). New York, Wiley-Interscience,
1972. p. 416.
112. Silverman, M. p. and H. :|_. Ehrlich. Microbial Formation
and Degradation of Minerals. Adv. Appl. Microbiol._j[: 153-
206, 1964.
-------
DRAFT
DO NOT QUOTE OR CITE
9. UNDESIRABLE EFFECTS
9.1 HUMAN
9.1.1 Hypersensitivity
Nickel dermatitis—the "nickel itch"—is a common malady among nickel
miners, smelters, refiners, and nickel-plating workers. Currently, how-
ever, nickel dermatitis is being reported frequently by non-industrial
populations who contact the metal in the course of their everyday
1 c 2
activities. Women have a high rate of nickel hypersensitivity, either
from greater susceptibility or greater exposure.
The symptoms of the skin eruption begin as an itching or burning
papular erythema in the web of the fingers and spread to the fingers,
wrists, and forearms. The clinical pattern of nickel dermatitis.progresses
from areas of direct contact with the metal, to selective symmetrical
areas involved when the skin eruption spreads to other areas of the body
3
which may have had no nickel contact.
In order to elicit epidermal sensitivity, it is necessary for the
nickel to be in contact with the skin, to penetrate the epidermis, and to
combine with a body protein. The leaching of nickel from objects is en-
hanced through the action of human sweat. The diffusion of divalent nickel
occurs at sweat duct and hair follicle openings, and it has a special
affinity for keratin , the protein of hair.
A s'tudy by Spruit4 indicated tnat divalent nickel • ;
reaches and is bound to the dermis. Sometimes nickel .dermatitis persists
for months following removal of all apparent nickel contact, which may
indicate fixation of nickel in the skin.
-------
DRAFT
DO NOT QUOTE OR CITE
The studies . to determine the extent of v-
nickel hypersensitivity have been on patients having eczema
rather than on the general population. Among persons seeking medical
attention for a skin eruption, about llpercent reacted positively to nickel on
skin testing. However, the prime question of true incidence in the general
population has not been answered, nor has the capacity of nickel to act as
5
a skin sensitizer been ascertained.
9.1.2 Nickel Carbonyl Toxicity
Nickel carbonyl [Ni(CO)4 ]is a colorless, volatile liquid organo-
nickel compound which is particularly dangerous if inhaled. The acute
inhalation toxicity of Ni(CO)^ is approximately 100 times greater than
that of carbon monoxide.
The clinical pattern of nickel carbonyl intoxication begins with •
symptoms such as frontal headache, vertigo, nausea, vomiting, and some-
times sternal or epigastric pain. Often a latent period
follows of from 12 to 36 hours during which these symptoms subside and the
patient feels better. After this, the more serious symptoms occur:
constrict!ve chest pain, cough, breathing difficulty, cyanosis, gastrointestinal
symptoms, and weakness. The temperature usually does not exceed 38.3°C (101°F);
2
n'te blood cell' count is less than 12,000 per mm £he pulse may be elevated; and
the patient may lapse into a terminal delirium. If the patient survives,
convalescence requires several months, during which the characteristic
symptom is muscular weakness.
-------
DRAFT
DO NOT QUOTE OR CITE
The diagnostic method employed for nickel carbonyl intoxication is to
measure the urinary
concentration of nickel during the first three days after exposure using
the following classifications: mild exposure, 10 yg/100 ml; moderately severe,
o
10-50 jig/100 ml; and severe exposure, 50 yg/100 ml. .
The pathology of nickel carbonyl poisoning has been explored in
autopsy studies of fatal cases. Death was usually attributed to respira-
tory failure, but cerebral edema and punctate cerebral hemorrhages were
often present al.so. A mild to moderate parenehymal degeneration was
g
observed in liver, kidneys, adrenal glands, and spleen.
After inhalation, nickel carbonyl can pass across the alveolar mem-
brane in either direction without metabolic alteration. In animal studies,
Ni(CO). that is inhaled or injected does not immediately decompose;
and :by either route of administration, the pulmonary parenchyma has been
found to be the target tissue for the compound. The lung is an excretory
organ for nickel carbonyl. The remainder of the Ni(CO). present in the
body slowly undergoes intracellular dissociation within red cells and other
tissues to liberate elemental nickel (N? ) and carbon monoxide. The Ni° becomes
Z+
zed to divalent nickel /and is released into the serum, from which it is gradually
cleared by the kidney and excreted. It has been suggested that the nickel
reacts with adenosinetriphosphate (ATP) to form a stable binary complex, and
that the acute toxicity of nickel carbonyl may derive, in part, from
inhibition of ATP utilization. ;:?-3
-------
DRAFT
DO NOT QUOTE OR CITE
Nickel carbonyl is not considered an environmental hazard for the
general public. However, the presence of the compound in cigarette smoke
may pose a problem of some chronic toxic effects among smokers.
-------
9.1.3 Carcinogens Is UKAr I
DO NOT QUOTE OR CITE
There have been epidemiological studies of cancer among nickel workers
in Males Norway, Germany, France, Russia, Japan, Canada, and the United
States. At least 327 cases of lung .cancer and 115 cases of nasal cancer
have occurred among workmen exposed .to the irrhalation of nickel compounds.'
*
It seems unlikely that any one nickel compound can be implicated as the •
sole carcinogenic factor, but rather several nickel compounds are carcinogenic
for man following chronic exposures by inhalation.
There seemed to be a qreater risk of cancer for the workers who were involved
in nickel processing than workers whose duties were removed from
the process. Among Welsh nickel workers, it was'found that most of the
cancers occurred among workers employed prior to 1924 when a
number of changes were made in the operation. One of these changes was tho
elimination of arsenic as an impurity in one of the process components. •
The latent period between time of employment in the nickel industry
and diagnosis of cancer varies in length from less than five years to more
than 40 years. Among the Welsh nickel workers, the average latent period
12,13.
for lung cancer was four years longer than for nasal cancer. Doll "repoVted
that susceptibility to induction of cancer of the nasal cavities increased
•• .'
with age at first exposure, but that susceptibility to induction of pulmonary
cancer was not similarly correlated.
There is currently little understanding of the exact mechanisms whereby
nickel compounds exert their carcinogenic effect. There are several
hypotheses regarding chemical initiation of carcinogenesis, however, and
these hypotheses are summarized in Table 9il. All of these possible .car-
cinogenic effects are postulated on the basis that nickel is able to freely
the
pass through cell membrane, and 70-90 percent of the metal is then concentrated in
q-s •
-------
Table 9.1. CURRENT HYPOTHESES REGARDINfa CHEMICAL INDUCTION OF CARCINOGENESIS
I. Genetic Mechanisms
A. Dirc•c^ modification of existing DNA ("sonatic
nutation"-;, in which replication .of chemically altered
* *
DI'A cause- inheritable, modifications, deletions, or re-
arrangements of the DNA nucleotide sequence, causing
pernanent changes in growth regulation
B. Alters.* isn 3 of D'-JA polvTEgrase, vhich tempora-
rily decre^'3-j the fidelity of DIIA replication, causing
nutations of the DI.'A genose
C. Ch^-icq.1 rodific.ition- of RNA. vhi:h is later
transcribed ir.ts DIIA that becor.ec integrated ir. the
host geno-e; this nay involve viral RIJA-prirr.ed
DKA polyr.=ra^e ("reverse transcriptase")
II.
A. • Cher.ical modification of HTJA or proteins
(e.g., histones and -cuclear acidic proteins) that
regulate • DI.'A template activity, causing- expression
of normally repressed portions of the DliA genor.e
B. Che.T.ical rodi fi cation of rJi'A or proteins.
causing depression of tur.or viruses or cncogenes
C. Carcinofren— induced ch25!~e.~ ir. irrsunclc^ris
or horEonal neohar.isnis , leading to preferential
proliferation of previously existing prencoplastic
or neoplastic cells
-------
NT NOT QUOTE OR CITE
the cell nucleus. The most common histopathologic types of respiratory
cancer in nickel workers have been epidermoid, anaplastic, and pleomorphic
carcinomas.
The carcinogenic effect of nickel seems to be enhanced by certain
physical conditions or the simultaneous occurrence of some other substances'.
*
The effect of nickel dust in the heated air of furnace rooms resulted in •
14
more lung cancer cases than were found among workers in other locations.
The question of synergistic effect of nickel and benzo[a]pyrene nas been
15 Ifi
raised because of animal study results on carcinogenesis. Cralley has
advanced a theory of metal interaction in asbestos carcinogenesis in which
he proposes that the asbestos fiber simply serves as a transport mechanism
for the introduction of nickel, chromium, and manganese into the tissues
and that the other metals enhance the carcinogenesis of nickel.
A possible interrelationship of nickel with certain parasites and viruses- in
the carcinogenic process has also been suggested; '• °
Though the hazard of nickel carcinogenesis seems relatively controlled
among nickel workers under the present industrial safety standards, the
hazard may still exist to some extent among cigarette smokers. Long term
exposure to small quantities of nickel carbonyl in cigarette smoke, along
with other toxic components present in the smoke, may contribute to the -hiqh
rates of lung cancer among smokers. :
-------
DRAFT
DO NOT QUOTE OR CITE
f\B
9.2 ANIMAL
9.2.1 Laboratory Animals
Nickel salts are relatively non-toxic by the oral route but quite
toxic when given intravenously. Less information is available regarding
toxicity by inhalation, except for nickel carbonyl.
The toxicity of inorganic nickel salts is summarized in Table 9.2.
The toxicity of nickel complexes and organonickel compounds will be
considered separately.
9.2.1.1. Inorganic Nickel by the Oral Route—The oral toxicity of nickel
sulfate for rabbits and dogs was established in the early 1800's by the
20
studies of Gmelin. Large oral doses of nickel salts resulted in gastro-
intestinal irritation with vomiting and diarrhea. Subcutaneous or
(r -8
-------
DRAFT
Table 9.2.
TOXICITY OF INORGANIC NICKEL COMPCu!
DO NOT QUOTE OR CITE
JNDS Hi ANIMALS19
Route of
Compound Formula Mol. Wt. Administration a Animal
Nickel Ni 58.71
Nickel acetate Ni(C2H.j02)2 202.84
Nickel carbonyl Ni(CO)4 170.75
Nickel chloride NiCl2 129.61
Nickel fluoborate
Nickel fluoride NiF2 96.71
Nickel nitrate Ni(N03)2 210.80
Nickel oxide NiO 74.71
Nickel perchlorgte
Nickel sulfamate
Nickel sulfate NiS04'6H20 262.89
hexahydrate
Nickel subsulfide Nt S2 240.25
ims
ims
ivn
orl
ims
inl
ivn
ivn
orl
ivn
orl
ims
ims
ivn
ipr
ipr
scu
ims
ims
rat
mouse
dog
guinea
Pig
rat
rat
rat
dog
rat
mouse
rat
rat
mouse
dog
mouse
mouse
dog
rat
mouse
Toxicity Data
TDLO:
TDLO:
TDLO:
LDLO:
TDLO:
LC50:
LD50:
LDLO:
LDLO:
LD50:
LD50:
TDLO:
TDLO:
TDLO:
TDLO:
LDLO:
LDLO:
TDLO:
TDLO:
110 mg/kg
800 mg/kg
10 mg/kg
5 mg/kg
420 mg/kg
240 mg/m3
22 mg/kg
10 mg/kg
500 mg/kg
130 ing/kg
1,650 mg/kg
180 mg/kg
400 mg/kg
7 mg/kg
100 mg/kg
250 mg/kg
500 mg/kg
90 mg/kg
200 mg/kg
ihl = inhalation; ims = intramuscular; ipr « intraperitoneal;
ivn - intravenous; orl = oral; scu = subcutaneous.
b
LC50 = lethal concentration (50% killed)
LD50 = lethal dose (50% killed)
LDLO = lowest published lethal dose
TDLO = lowest published toxic dose
-------
DRAFT •
00 NOT QUOTE OR CITE
intravenous administration is also known to produce gastroenteritis. In
dogs, central nervous system effects including tremor, spasmodic movements
and paralysis have been reported. A lethal oral dose of nickel salt for
a dog contains approximately 500 mg/k'g of nickel. The metal itself is
tolerated at 1 to 3 g/kg by dcgs.
Young rats tolerated dietary levels of 250, -500 or 1000pg/g nickel as
nickel carbonate, nickel soaps or raney nickel for eight weeks without effect
on growth rate. Absorption and retention was greatest with the carbonate.
Highest tissue concentrations were 140-360ug/g in bone; other tissues
?i
contained 10-50 vg/§- A level of 250yg/g as nickel catalyst was without .
effect in a 16 month feeding?2 For the first eight months, nickel tissue
concentration increased; it then fell despite continued intake. Once
nickel, was withdrawn from the diet, it could not be detected after 20
22
days in feces or after 40 days in urine.
Nickel acetate was judged to be inert at the 5 yg/glevel in the diet
23 24
of mice in terms of effects; on growth, survival,and tumor incidence. '
No deleterious effects on growth, behavior, hemoglobin concentrations,
red cell* or white cell counts were observed in monkeys (Macaca s inicus)
21 "
fed nickel at 250, 500,or 1000 yg/gfor 24 weeks. Compounds included nickel
catalyst, nickel soap and nickel carbonate. Analyses of nickel content of
tissues or pathological findings were not reported.
Toxicity by the oral route was observed in male Holstein calves given
25
nickel carbonate in theirdiet. Animals fed nickel at 62.5 pg/g showed
normal growth and weight gain. At 250 ^g/g food intake and growth were
slightly reduced; and at lOOQyg/gthe reduction was marked. At the highest
-------
concentration, the animals appeared smaller, but were not emaciated.
When nickel was removed from diet of the animals fed 1000 pg/g,their
weight gain was equal to that of the others, of the organs examined, only the
kidneys showed abnormalities. This was true in all arouos. but
pyelonephritis (inflammation of kidney and surroundings) was observed only at
1000yg/g.
With chicks fed diets containing nickel sulfate or acetate, growth
was significantly reduced between 300 and 700ng/g with further reduction
nc
at 900 to l,300yg/g~ Nitrogen balance was negative above 500ug/g. Paired
feeding at 1,100 yg/g showed that growth was not affected, but the nitrogen
balance remained negative in the animals receiving nickel.
Rabbits given nickel chloride, 500 ug/day for 5 months, exhibited
depressed liver glycogen, elevated muscle glycogen, and d prolonged
27
hyperglycemia following galactose loading.
Parenterally administered nickel is excreted mainly in the urine.
Immediately following injection of nickel-63 in the rat the distribution of
28 :
radrelabelled nickel depends directly on blood volume. After 48 hours,
however, all radioactivity disappears from whole blood and plasma. After
72 hours, the label is present only in the kidneys and by this time 61 percent
has been excreted in the urine and 5.9 percent in the feces.
-------
DO NOT QUOTE OR CITE
In studies on the kinetics of nickel-63 metabolism in rats and rabbits,
•*39 •
Onkelinx et al. determined that the radiolabelled metal was rapidly ^
cleared from plasma or serum during the first 2 days following a single
intravenous injection. Seventy-eight percent was excreted in the urine
during the first day in rabbits. Three days were required for the urinary
percent
excretion of78/ of the administered dose in rats. Disappearance of the
nickel-63 from the serum was at a much lower rate from day 3 to day 7.
Measurements of nickel-63 distribution and excretion suggested that in both
species nickel-63 is diluted within two compartments and eliminated by first
order kinetics. This two compartment model was verified by its ability to
4
predict nickel-63 concentrations in serum or plasma with continuous
infusion or repeated daily injections. ^
Parenteral injection of nickelous chloride has been reported by Berenshteypri
30'. -'
and Shifrina to increase or decrease blood glucose depending upon dose. Clary^
31
and Vigniati" have observed immediate development of hyperglycemia following
intraperitoneal injection of nickel chloride in rats at 10 to 80 mg/Kg.
The hyperglycemia could be prevented by simultaneous administration of
insulin.
32
9.2.1.3. Inhalation of Inorganic Nickel--Bingham et al. have shown
that exposure of rats to nickel oxide and nickel chloride by inhalation
at a concentration of approximately 100 yq/m for 12 hours daily and six
days per week resulted in the following effects: After two weeks, inhalation
of nickel oxide produced a marked increase in the number of alveolar
macrophages in the lungs as compared to controls. Nickelous chloride did
not produce such an effect but resulted in pathological respiratory changes
ifter four to six weeks exposure. The bronchial epithelium was hyperplastic
-------
with evidence of marked mucous secretion, and peribronchial infiltration
was also seen. With longer exposure four to six weeks, to nickel oxide, the
cellular infiltration seen earlier subsided, leaving thickened alveolar
walls distributed throughout the lungs and occassionally in the bronchi.
Macrophages were variable in size with a shift to smaller cell diameters.
op
The experiments of Bingham ejt al_. were performed at approximately one
*
tenth of the current Threshold Limit Value for nickel which is
3
l,000-~g/m • A threshold Limit Value (TLV) represents an airborne
concentration of a substance to which nearly all workers may be repeatedly
exposed occupationally, day after day, without adverse effect.
Although the changes observed may not be of pathologic
significance or irreversible, they occur at such low levels as to suggest
the need for additional investigation if the current TLV is to be considered
valid.
33
Sanders et al. using Syrian golden hamsters demonstrated that more
nickel oxide particles were found free in alveolar lumens when pulmonary
clearance was impaired by exposure to cigarette smoke. This effect might
be expected to potentiate adverse responses to nickel oxide although none
were described.
34
In another study with Syrian golden hamsters Wehner and Craig
.demonstrated, in agreement with the ICRP Committee II Task Force on Lung
i 35
Dynamics, that nickel oxide displays moderate lung retention. Almost
20 percent of the inhaled nickel oxide remained after initial clearance and,
of this, 45 percent was still present after 45 days. Nickel oxide
3
concentrations ranged from 10,000 to 190,000/g/m . The compound was not
acutely toxic at any level employed. However, prolonged lung retention
increases the concern over the possibility of inducing chronic lung changes.
-------
.9.2.1.4 Toxicity of Nickel Complexes and Organic Nickel Compounds—Table 9.3
and 9.4 summarize toxicity studies that have been reported for nickel
complexes and organic nickel compounds in experimental animals. In the
"57 '
studies by Nofre et al., Joesten and Hill, and Haro et al ,^ the acute
toxic effects of several nickel complexes were compared to related nickel
salts. Depending upon the nature of the complex, toxicity was enhanced or
reduced, usually in a predictable manner, For example, as shown in Table
9.3, the LD50 for nickel with disodium EDTA and for nickelocene was
greater than that for nickel sulfate .nickel acetate,or nickel chloride,
On the other hand,the LD50 for the complex of nickel perchlorate with
the insecticidejoctamethylpyrophosphoramide.was about one-seventh of that /
for nickel perchlorate.
By far, the greatest amount of toxicological information on pi-complexes
of nickel is on nickel carbonyl.Table 9.4 summarizes toxicity studies of
this compound in experimental animals. The first inhalation studies on
4b,46
this compound demonstrated that it is approximately 100 times as toxic
as carbon monoxide. Symptoms of exposure in experimental animals include
difficult and rapid breathing, cyanosis, fever, apathy, aversion to food,
vomiting,diarrhea, and occasionally, hind limb paralysis. Generalized
convulsions are frequently a terminal effect. The pathologic lesions
that have been observed to develop in experimental animals following
exposure to nickel carbonyl are summarized in Table 9.5. These studies indicate
that the pulmonary parenchyma is the target tissue
for nickel carbonyl regardless of the route of exposure. The time
course of the pulmonary response following exposure to nickel carbonyl is
DRAFT
DO NOT QUOTE OR CITE
-------
Toxicity Studies of Nickel Complexes in Experimental Animals
Compound
Nickel chloride hexahydrate
Nickel-disodium-EDTA^
Nickel sulfate heptahydrate
Nickel perchlorate-30MPAc
Nickel perchlorate hexahydrate
Nickelocene^
Nickel acetate
Nickelocene
Nickel acetate
Nickelocene
Nickel acetate
Nickelocene
Nickel acetate
Ni-DBDTCe
Route of
administration
Intraperitoneal
Intraperitoneal
Intraperitoneal
Intraperitoneal
Intraperitoneal
Intraperitoneal
Intraperitoneal
Intraperitoneal
Intraperitoneal
Oral
Oral
Oral
Oral
Oral
Animal
Mouse
Mouse
Mouse
Mouse
Mouse
Mouse
Mouse
Rat
Rat
Mouse
Mouse
Rat
Rat
Mouse
^50
1*8 mg/kg
600 mg/kg
38 mg/kg
15 mg/kg
100 mg/kg
86 mg/kg
32 mg/kg
50 mg/kg
23 mg/kg
600 mg/kg
1*20 mg/kg
500 mg/kg
350 mg/kg
(MTD =0.1
O
o
-2.
^^
'S^
S-
o
73
^\
m
mg/)
Tnvfistiqator
Franz 36
Nofre et al.
37
Joesten and Hill-
38
Haro et al.
39
Innes et al.
40
data permit comparisons of the relative toxicities of nickel complexes and nickel salts.
= ethylenediaminetetraacetate. . eDBDTC = dibutyldithiocarbamate.
COMPA = octamethylpyrophosphoraiaide. . /MTD (maximal tolerated dose) = maximal oral dose resulting
"Nickel dicyclopentadiene. in zero mortality after 19 daily doses.
-------
Table 9.4
TOXICITY STUDIES OF NICKEL CARBONYL IN EXPERIMENTAL ANIMALS
Route of
administration
Subcutaneous
Intravenous
• Intravenous
: Subcutaneous
Inhalation
«alation
alation
Inhalation
" Inhalation
Inhalation
Inhalation
Inhalation
Inhalation
Intravenous
Subcutaneous
Int-raperitoneal
Inhalation
Vlation
Animal
Rabbit
Rabbit
Dog
Dog
Dog
Rabbit
Cat
Dog
Mouse
Rat
Mouse
Rat
Cat
Mouse
Mouse
Rat '
Rat
Mouse
Rat
Dog
Rat
Rat
Rat
Rat
Rat
Mouse
Lethal
dose nn MHT QUOTE
\J\J 1 • ~ • • v
LDioo = 25 me/ks
LD100 = 1*0 mg/kg
LDinn = 33 mS/kg
xww
LD100 = 33 mg/kg
LD100 = 50 mg/kg
LD80 =
LD80 =
LDgO =
2 •
LD50 =
LD50 =
LD50 =
l.U mg/liter for 50 min
3.0 mg/liter for 75 min
2.7 mg/liter for. 75 min
0.17 mg/liter for 5 min
0.9 mg/liter for 30 min
0.067 mg/liter for 30 min
0.2U mg/liter for 30 min
0.19 mg/liter for 30 min
LD100 =0.2 mg/liter for 120 min
LD0 = 0.01 mg/liter for 120 min
LD100 =0-3 mg/liter for 20 min
LD50 =
LDep =
ED65 =
LDQO =
LD3Q =
LD5Q =
LD50 =
LD50 =
LD5Q =
LD10Q =
LDQ = 0
0.1 mg/1 for 20 rain
O.Ql*8 mg/liter for 30 min
0.50 mg/liter for 3(. min
2.5 mg/liter for 30 min
0.51 mg/liter for 30 min
65 mg/kg
6l rag/kg
38 mg/kg
0.58 mg/liter for 15 min
0.1 mg/liter for 120 min
.01 mg/liter for 120 min
c
Investigator
McKendrick and
41
Snodgrass
Hanriot and Richet-
42
Langlois
^ 44
43
Armit
Garland
46
Barnes and Denz-
47
48
Kincaid et al. '
,- 49
Sanotskii
Ghiringhelli
50
West and Sunderman-
Sunderman et al.
Sunderman- 5?
51
Hackett
and Sunderman
54
Sanina
55
-------
PATHOLOGICAL LESIONS-FOLLOWING ACUTE EXPOSURE OF EXPERIMENTAL ANIMALS TO NICKEL C.ARBONYL
Route of
adninistrati on Animal Dose
Inhalation
Observation
period after
exposure Observations
Inhalation
Inhalation
Rabbit 1.1* mg/liter for 50 min 1-5 days Lungs: intra-alveolar hemorrhage, edeiia, ar.d
exudate and alveolar cell degeneration;
adrenals,: henorrhages; brain: perivascular
leukocytosis; and neuronal degeneration
Rat 0.9 mg/liter for 30 min 2 hr-1 year Lungs: at 2-12 hr, capillary congestion and
interstitial edema; at 1-3
-------
.o continued
Route of
administration Animal Dose
Observation
period after
exposure
Observations
Intravenous Rat 65 mg/kg 0.1 hr-21 days Lungs: at 1-U hr, perivascular edema; at 2-5
days, severe pneumonitis with intra-alveolar
edema, hemorrhage, subpleural consolidation,
hypertrophy and hyperplasia of alveolar lining
cells, and focal adenomatous proliferation; at.
8 days, interstitial fibroblastic proliferation;
liver, kidneys, and adrenals: congestion,
vacuolization, and edema
Intravenous Rat 65 mg/kg 0.5 hr-8 days Lungs: ultrastructural alterations, including
edema of endothelial cells at 6 hr and massive
hypertrophy of membranous and granular pneuno-
cytes at 2-6 days
Intravenous Rat 65 mg/kg 0.5 hr-6 days Liver: ultrastructural alterations of.hepsto^-
cytes including nucleolar distortions at 2-2L hr,
dilatation of rough endoplasmic reticulun at
1-U days, and cytoplasmic inclusion bodies at
h-6 days y
Hackett and
Sunderman
54
Hackett
and Sunderman-
56
Hackett
and Sunderman- 57
-------
as follows:
,o 1 hour - edema develops 1n the alveolar septa! interstitlum
o 1 day - polymorphonucleur leukocytes accumulate 1n the tissues
around the bronchioles and alveolar septa and to a
lesser extent 1n the alveolar spaces; abnormal
multiplication of the bronchiolar epithelium and -
alveolar lining cells are observed
o 2 to 5 days - severe intra-alveolar edema with focal hemorrhage
and changes in the alveolar epithelal cells
o 3 to 5 days - death usually occurs \
o 6 to 10 days - in surviving animals alveolar epltheial cell
alterations regress toward normal; however there are
.still some sites of abnormal cell multiplication within'
the alveola and in connective tissue
o 14 to 21 days - the functional elements of the lung are essentially
normal except for interstitial flbrosis
Pathological findings In other organs after acute exposure of animals
to nickel carbonyl are generally less severe. Focal hemorrhage, congestion,
edema, mild inflammation, and vacuolization have been reported in brain,
liver, kidneys, adrenals, spleen, and pancreas. Dilatation of rough
endoplasmic reticulum Is consistently observed in the hepatic parenchyma
(functional parts of the liver). Nucleolar alterations also develop within
hepatocytes between two to 24 hours after exposure to nickel carbonyl.
-------
DRAFT
Table 9,5. 00 NOT QUOTE. OR
Radiotracer ' and gas chromatographic studies^
have demonstrated that nickel carbonyl can pass across the alveolar
membrane in either direction without metabolic alteration. Nickel carbonyl
that is.inhaled or injected does not immediately decompose. In the rat
approximately 36 percent nf an inifirt.ert dnse of nickel carbonvl is PvrrotoH oit.Mn
4 hours, jn tne expired breath. Thus, the lung is a major excretory organ
for nickel carbonyl. The remainder of the nickel carbonyl slowly
decomposes within red cells and other tissues to liberate elemental nickel
• (Ni°) and carbon monoxide. The carbon monoxide is bound to hemoglobin and
is transported to the lungs for exhalation;within six hours following the
injection of nickel carbonyl,approximately 49' percent of the nickel carhonyl
moiety
is expired as carbon monoxide and 1 percent as carbon dioxide. In the
rat carbon monoxide saturation of hemoglobin peaks during the second hour,
and thereafter decreases exponentially with a half-time of approximately
90 minutes.paralleling the exhalation rate of carbon monoxide. The nickel
(Ni°) that is released from nickel carbonyl is oxidized intracellularly
2+
to Ni • and is released for binding to blood serum components as previously
described. Nickel is rapidly cleared from the serum and excreted by the
kidneys. In the rat, an average of 23 percent of nickel, injected as nickel .
carbonyl, is excreted in the urine within 12 hours, and an average of 27 percent,
within 24 hours. Only approximately 0.2 percent of Injected nickel is excreted in
the bile within 6 hours. By the end of 4 days, an average of 38 percent cf injected
nickel can be recovered in breath, 31 percent in urine, and 2 percent in frees.
wWhin homogenates of lung and liver, small portions of the intracellular nickel
-------
DO NOT QUOTE OR CITE
remain bound to DNA, RNA, and proteins. These apparent associations of
nickel with nucleic acids and proteins may occur secondarily during the
homogenization and extraction procedures.
It has been suggested by S. and coworkersj4'5G'59 that
lung lesions may result from damage produced during transit of nickel
carbonyl across the alveolar epithelium rather than from the toxicity of
the small amount of nickel that remains in the lungs after 24 hours .On this
for*
basis the optimal therapy / acute nickel carbonyl poisoning would
theoretically be to minimize the pulmonary exhalation/of nickel carbonyl
and to mobilize nickel carbonyl and carbon monoxide by extracorporeal gas
exchange. To date, this approach to therapy of nicklel carbonyl poisoning
has not been tested either in experimental animals or in man. There has,
however, been considerable success in the therapeutic use of chelating drugs.
Uimercaprol (BAL), thloctic acid, peniclllamine,
and sodium diethyldithiocarbamate (dithiocarb) have all been reported to be
beneficial in acute nickel carbonyl poisoning in experimental animals.
Sodium diethyldithiocarbamate is by far the most effective therapeutic
agent on the basis of animal experiments.
Studies on the biochemical mechanisms of nickel carbonyl toxicity
are summarized in Table 9.6.
Sunderman ' suggested that the acute toxicity of nickel carbonyl may
result, in part, from inhibition of ATP utilization. This suggestion
49
was prompted by the following studies: Sanotskii determined that the
DRAFT
DO NOT QUOTE OR CITE
-------
OF BIOCHEMICAL MECHANISMS OF NICKEL
Route of
administration
Inhalation
Inhalation and
Intravenous
Intravenous
Intravenous
Intravenous
Intravenous
Intravenous
Intravenous
Intravenous
Intravenous
Intravenous
Animal Observations
Mouse Diminution of body oxygen consumption
Rat Inhibition of phenothiazine induction of
benzopyrene hydroxylase in lungs and liver
Rat Inhibition of cortisone induction of hepatic
tryptophan pyrrolase '
Rat Inhibition of phenobarbital induction of
hepatic cytochrome
Rat Inhibition of RNA polymerase in hepatic
nuclei
Rat Inhibition of orotic acid incorporation
intr iiepatic RNA
Rat Inhibition of RNA synthesis by hepatic
chromatin-RNA polymerase complex
Rat Inhibition of phenobarbital induction of
aminopyrine demethylase in lungs and liver
Rat Slight inhibition of leucine incorporation
into hepatic mierosomal proteins
Rat Increased hepatic ATP concentration
Rat Inhibition of RNA synthesis in liver,
but not in lungs
TOXICITY IN EXPERIMENTAL ANIMALS
Sanotskii- 49
Sunderman "'
Sundermajr
62
Sunderman 53
Sunderman and
Esfahani 54
Beach and Sunderman .
66
Beach and Sunderman
Sunderman and
Leibman 67
65
Sunderman
Sunderman-
Witschi
68
69
CITS
-------
DRAFT
DO NOT QUCKt OR CHE
whole body consumption of oxygen in mice was immediately diminished
following exposure to nickel carbonyl and remained diminished for 3 days.
CQ
Sunderman found that nickel carbonyl resulted.in increased hepatic
ATP concentrations in rats that were killed 30 minutes or 24 hours after
injection. That divalent-nickel inhibition of hepatic ATPase activity
may be involved is suggested by in vitro studies showing inhibition of
ATPase activity in rat liver microsomes; Divalent nickel in millimolar
concentrations also inhibits ATPase activity of cilia of Tetrahymena
pyriformis, and ATPase activity of sheep alveolar macrophage cells
in vitro and brain capillaries in vivo ' . Nickel has also been
reported to reversibly inactivate ATP:creatine phosphotransferase in
vitro at a concentration of 0.0005 molar. As previously ment.inned. Sianet et
al. -have shown that nickel reacts jn vitro with ATP to form a stable
binary complex. Such a stable nickel-ATP complex might reversibly
inhibit ATP utilization by saturating the binding sites for ATP on ATPase
result in
and creatine phosphotransferase. This could/acute toxicity as observed
68
with nickel carbonyl.
9.2.1.5. Nickel Sensitization in Experimental Animals and Lymphocyte
Cultures—Several investigators have reported experimental sensitization
to n.ickel using guinea pigs- ' " Several others have been unable to
confirm these findings . ' Sodium lauryl sulfate has been used with
nickel sulfate solutions to sensitize experimental animals by repeated
topical application • However, this treatment may produce local
79
irritation rather than allergic reactions. No technique is available
for consistent induction of delayed hypersensitivity in animals.
-------
n, DRAFT
DO NOT QUOTE OR CITE
Several studies suggest that lymphocyte transformation j[n_ vitro may
0
on on 09
be a sensitive method for the detection of delayed human hypersensitivity. ' '
82 83 84
Some investigators have questioned the specificity of the test;
however, more recent reports are favorable.
9.2.1.6 Nickel Carcinogenesis in Experimental Animals--Experimental
systems that have been used to study nickel carcinogenesis in animals
Rfi 87
are listed in Table 9.7. Localized malignant sarcomas ' are observed
with parenteral administration of metallic nickel dust or pellets to
QO nn
rats, guinea pigs, and rabbits. ' Nickel subsulfide (Ni-S^) injected
intramuscularly into rats is a very potent inducer of rhabdomyosarcomas
(malignant muscle tumors). Epidermoid carcinomas and adenocarcinomas
are observed in the sinuses of cats after implantation of nickel sulfide
disks. Pulmonary carcinomas in rats have been reported after inhalation
91 92
of nickel dust, or nickel carbonyl. Carcinomas and sarcomas have
been reported in diverse organs—including liver and kidney—of rats
93 '
that received multiple intravenous injection of nickel carbonyl.
Carcinogenic synergism between some nickel compounds (NiO and Ni-S^)
and polycyclic aromatic hydrocarbons (methylcholanthrene and benzo[a]pyrene). '
Thus, nickel carcinogenesis has been demonstrated in several species of
animals after administration by inhalation or other parenteral routes.
However, there is no experimental evidence that nickel compounds are
carcinogenic when administered orally or percutaneously.
5
As pointed out in the Report by the National Academy of Sciences,
the carcinogenicities of the nickel compounds in rats appear to be
inversely correlated with their solubilities in aqueous media. In
-------
Table 9.7. EXPERIMENTAL MODELS OF NICKEL CARCINOGENESIS
85
Substances
Nickel dust
Nickel dust
Nickel dust
Nickel carbonyl
Nickel pellets
-o
N Ni,S9 and NiO
-£L O c.
dust
NiO and methyl
cholanthrene
Nickel dust
Nickelocene
Ni'S2 disks
Ni3$2 and
Benzo[a]pyrene
Nickelocene
Animals
Mice
Rats and rabbits
Guinea pigs
Rats
Rats
Rats and mice
Rats
Rats
Rats
Cats
Rats
Hamster
Route of
administration
Inhalation
Intravenous and
intrapleural
Inhalation
Inhalation
Subcutaneous
Intramuscular
Intratracheal
Intramuscular
Intramuscular
Sinus implants
Intramuscular
Intramuscular
Tumors
Unspecified
Sarcomas
Anaplastic and adenocarcinomas
Squamous cell carcinomas
anaplastic carcinomas, and
adenocarcinomas
Sarcomas
Sarcomas
Squamous cell carcinomas
Sarcomas
Sarcomas
Squamous cell carcinomas,
adenocarcinomas & sarcomas
Sarcomas
Sarcomas
c5
CD
/•O
t '
0
•-H
m
V.
-_ ._,
-------
-0
N1
(n
85
DRAF
Table 9.7 (continued). EXPERIMENTAL MODELS OF NICKEL CARCINOGENESIS" *yj »,nr rj!;,v ..
l/U i,\,; •'/•;i.;i ;.
Substances
Animals
Route of
administration
Tumors
Nickel carbonyl Rats
Nickel dust •• Rats
Ni^S,, and ' " "" Rats
benzo[a]pyrene
Nickel ocene
Rats
Fetal rats
Intravenous
Carcinomas and sarcomas
Intrathoracic and Mesotheliomas
intraperitonea"!
Intratracheal Squamous cell carcinomas
Subcutaneous
Transplacental
Fibrosarcomas
Malignant neurinoma
-------
DO NOT QUOTE OR CITE
general, the strong carcinogens, nickel subsulfide and nickel oxide are
practically insoluble in aqueous media, while the noncarcinogens, nickel
sulfate, nickel chloride, and nickel ammonium sulfate are very soluble.
Exceptions to this rule include nickel sulfide which has low solubility
and was not carcinogenic in one study, and nickel acetate which is
relatively soluble and only moderately carcinogenic in three studies.
The possibility that induction of sarcomas in rats might constitute
a nonspecific reaction to intramuscular injection of insoluble metallic
dust was investigated by Sunderman et al. using nickel subsulfide.
Intramuscular injection of equimolar quantities of nickel subsulfide,
manganese, chromium, copper, and aluminum dusts in Fisher rats resulted
in development of sarcomas at the injection site in 23 of 24 rats that
received nickel subsulfide. No such neoplasms were observed in similar
groups of rats that received manganese, chromium, copper, and aluminum.
Particular attention has been focused on nickel carbonyl because of
its extreme toxicity and its widespread use. Neoplasms have been
induced in rats after administration of nickel carbonyl by inhalation
and by parenteral injection. These pulmonary carcinomas closely resemble
the lung cancers that develop in nickel workers. However, from an
experimental point of view, the latent period for induction of lung
neoplasms is long, 24 to 27 months, and the incidence of lung neoplasms
— oc
is low 4 to 21 percent in 2 year survivors.
Investigations of the induction of sarcomas in rats by intramuscular
injections of nickel subsulfide, Ni-Sp, are summarized in Table 9.8. In
investigations on the carcinogenicity of various metallic constituents
-------
Table 9.8. INDUCTION OF SARCOMAS IN RATS BY INTRAMUSCULAR INJECTIONS OF
DRAFT
Form and dosage
of Ni2S2
Dust,
Dust,
Disks
Chips
Dust,
Dust,
Disks
Dust',
40 mg
20 mg
, 500 mg
, 500 mg
20 mg
10 mg
, 250 mg
10 mg
Strain of rat
Wistar
Fischer
Fischer
Fischer
Fischer
Fischer
X^UM. un Ult
Observations
Sarcoma incidence, 89% (80% rhabdomyosarcomas, 20% fibrosarcomas;
lung metastases, 76%
No effect of physical form of Ni~S? implant on sarcoma "incidence
(71-95%) or lung metastases (69-tOO%)
Precancerous changes in muscle cells: nucleolar hypertrophy;
mitoses; evolution of myoblasts
Tumor susceptibility not sex-dependent; greatest at age of 2 months
promoted by methandrostenolens
Tumorigenesis prevented by excision of Mi'S,, disks within 6 days
after implantation
Higher sarcoma incidence after intramuscular injection (80%) than
Disks, 250 mg
Dust, 20 mg
Dust, 10 mg
Dust, 20 mg
3 strains
Fischer
Sprague-Dawley
after subcutaneous (44%) or intraperitoneal (24%) injection,
inhibited muscle tumorigenes is
Fischer and hooded rats more susceptible to Ni-S? sarcomas than
Bethesda black rats.
Tumor-specific antibodies in serum from rats with Ni-^Sp sarcomas
Sarcoma incidence, 37%; description of ultrastructure of
rhabdomyosarcomas
Dust, 10 mg
Fischer
Arginase activity much higher in Ni.,S2 rhabdomyosarcomas than in
adult or embryonic muscle
-------
Table 9.8 (continued). INDUCTION OF SARCOMAS IN RATS BY INTRAMUSCULAR INJECTION OF Ni
96
Form and dosage
of Ni'3S2
Strain of rat
Observations
Dust, 3.3 and 10 mg Fischer
Dust, 20 mg
Dust, 2.5 mg
Dust, 20 mg
Fischer
Fischer
Fischer
At 3.3 mg/, mean survival time longer (42 wk) than at 10 mg
(36 wk); sarcoma incidence not affected (97% and 85%)
Sarcoma incidence, 100% (81% rhabdomyosarcomas, 19% fibro-
sarcomas); lung metastases, 57%; survival time, 33 ^ 5 wk
Sarcoma incidence, 96%; induction of sarcomas by Ni.^
antagonized by simultaneous injection of manganese dust;
Scanning electron microscopy demonstrated chromosomal
abnormalities in a nickel sulfide-induced sarcoma
r, DRAFT
Co NOT QUOTE OR CITE
-------
of refinery dust (Ni'3S2, NiO, NiSo4 ' 6H20, CoS, CoO, CuS, Cu2$, CuO,
97
FeS, FeO, and Fe^O,), Gilman identified nickel subsulfide as the most
c *
carcinogenic component.
Table 9.9 summarizes several studies of the induction of sarcomas
" f
in rats by intramuscular or subcutaneous implantation of metallic nickel
QO
'r- as pellets, dust, or sponge. Friedmann and Bird have reported that
rhabdomyosarcomas (malignant muscle tumors) induced by metallic nickel
C.. •
are indistinguishable from those induced by Ni-Sp.
87 99
Heath et al. and Webb et al. ' have investigated the subcellular
distribution and binding of nickel in rhabdomyosarcomas induced by Ni
dust. They found that 70-90 percent of the nickel content of rhabdomyosarcoma
87
cells is intranuclear, bound to DNA and RNA. Webb and associates
have shown that at least 50 percent of the nickel within rhabdomyosarcoma
99
cell nuclei is in the nucleolar fraction. The intranucleolar localization
of nickel may have implications in the induction of rhabdomyosarcomas.
It should be noted that Kasprzak and Marchow recently published a
comprehensive review of the literature on experimental carcinogenesis
with nickel sulfide.
9.2.1.7 Possible Mechanisms of Nickel Carcinogenesis—The mechanisms
whereby nickel enters target cells is undoubtedly important in the
etiology of nickel carcinogenesis. It appears likely that at least two
transmembrane mechanisms are operative; one involving penetration of the
intact compound and the other involving transport of a soluble complex
species. Because of its lipid solubility, nickel carbonyl is able to
pass across cell membranes without metabolic alteration. ' ' This
ability is presumed to be responsible for the extreme toxicity of the
-------
Table 9.9
INDUCTION OF SARCOMAS IN RATS BY INTRAMUSCULAR OR SUBCUTANEOUS INJECTION OF METALLIC NICKEL
85
Ui
O
Form and
dosage of nickel
4 pellets
(2x2 mm) subcutaneously
dust (28 mg) intramuscularly
dust (28 mg) intramuscularly
sponge (20 mg) intramuscularly
powder (5 mg) intramuscularly
6 times at 4-wk intervals
dust (28mg) intramuscularly
dust (5 mg) intramuscularly
5 times at 4-wk intervals
Strain
of rats
Wistar
Hooded
Hooded
Sprague-
Dawley
Fischer
Hooded
Fischer
Observations
Fibrosarcoma incidence, 50%
Rhabdomyosarcoma incidence, 100%
lymph node metastases, 30%
Nickel bound to DNA and RNA in
rhabdomyosarcoma nuclei
Rhabdomyosarcoma incidence, 24%
^
Sarcoma incidence, 76%; latent period
6-12 months
Intranuclear nickel in rhabdomyosarcoma
cells is 53% in nucleolar fraction
Sarcoma incidence, 50-75%
o
~'3
'
-------
DRAFT
:.:0 NOT QUOTE OR CITE
compound. Nickel carbonyl also decomposes extracellularly to liberate
Ni, which can be taken up and oxidized to Ni intracellularly, ' It
appears that nickelocene is also able to penetrate cellular membranes
102
without decomposition and then exert its toxic effects. Following
intramuscular injection of insoluble inorganic carcinogens, such as
nickel dust and nickel sulfide, these compounds are presumed to be
deposited extracellularly and to dissolve slowly in the extracellular
fluid. The study of Singh and Gilman suggests that a diffusible
intermediate complex is involved in the intracellular transport of
104
nickel subsulfide. In studies with nickel dust, Heath et al. suggested
that metal-serum protein complexes, adsorbed at the surface of the
myoblast, may enter the cells by endocytosis and that later hydrolysis
of the carrier proteins by lysosomal proteinases might lead to intrac.ellular
release and redistribution of the electrophilic metal ion. In 1972,
Webb et al. ' suggested an alternative hypothesis that complexes of
nickel with small 'molecules play key roles as intermediates in the
intracellular transport of nickel. They found, that nickel dust incubated
with rat muscle homogenates slowly dissolves and becomes complexed
almost entirely (90 percent) with ultrafiltfcrable molecules. The
ultrafiltrable nickel complexes obtained jji vitro were similar to those.
formed when nickel implants slowly dissolved in muscle in vivo. .
I QO
Weinzierl and Webb speculated that myoblasts involved in repair of
muscle injury may take up the diffusible nickel complexes and undergo
neoplastic transformation. The uptake of diffusible nickel-63 complexes
was subsequently demonstrated using mouse dermal fibroblasts in tissue
culture.109
-------
Once entrance to the cell is gained, the intracellular biochemical
2+
effects of the Ni ions become an important aspect of nickel carcinogenesis,
The biochemical alterations that develop in rats after administration of
cy cc
nickel carbonyl have been investigated by Sunderman et al. ' Nickel
carbonyl was found to inhibit the induction of several enzymes in lung and
liver.62'63'67'110 Nickel carbonyl did not affect substrate (tryptophan)
induction of hepatic tryptophan pyrrolase, but did impair hormonal
(cortisone) induction of tryptophan pyrrolase. This suggested that
nickel carbonyl may produce a metabolic block at the level of messenger
cp
RNA. Nickel carbonyl also inhibited phenothiazine induction of
benzopyrene hydroxylase and phenobarbital induction of cytochrome
and aminopyrine demethylase in liver. It was subsequently determined
that 24 hours after injection of an ID™ of nickel carbonyl, there was 60
percent inhibition of DNA-dependent RNA-polymerase activity in hepatic
64
nuclei and 75 percent inhibition of RNA synthesis, as measured by
65
incorporation of carbon-14 labelled orotic acid into RNA. Under the
same conditions, nickel carbonyl produced only 8 percent reduction of
hepatic protein synthesis, as measured by incorporation of carbon-14
labelled leucine into microsomal proteins. Using a chromatin-RNA
polymerase complex that was prepared from hepatic nuclei from rats
exposed to nickel carbonyl, Beach and Sunderman demonstrated that
inhibition of RNA synthesis persists after disruption of the nuclei.
Inhibition resulting from impaired transport of RNA precursors across
the nuclear membrane was thus excluded. Witschin independently confirmed
the inhibitory effect of nickel carbonyl on hepatic RNA synthesis.
-------
n,
00 NOT fjiJOTE OR CITE
The intracellular distribution of nickel in nickel-induced rhabdomyosarcomas
has been studied by Webb et al. who found that a major portion
(70-90 percent) of the nickel is within the nucleus. Subfractionization
indicated that an average of 53 percent (range, 41-63 percent) of
nuclear nickel was contained in the nucleolar fraction, the remainder
distributed equally between the nuclear sap and the chromatin fractions.
Similar observations were made by Webb and Weinzierl in mouse dermal
fibroblasts grown in vitro in the presence of nickel-63 complexes.
These observations may relate to the findings of Beach and Sunderman
that nickel is bound to an RNA polymerase-chromatin complex which can
be isolated from hepatocyte nuclei of rats treated with nickel carbonyl.
112
Treagan and Furst have demonstrated that addition of nickel chloride
to tissue cultures of mouse L-929 cells inhibits their capacity to synthesize
interferon and antiviral protein following inoculation with Newcastle
disease virus. This finding may have significance with regard to viral- i
113
induced neoplastic transformation. Basrur and Gilman and Weierenga
114
and Basrur have shown that nickel sulfide inhibits mitotic activity and
induces abnormal mitotic figures in embryonic muscle cells. Their
findings suggest that nickel may alter gene replication and the control
of cell division. Although there has been considerable
speculation, ~ the exact mechanisms whereby nickel compounds exert
their carcinogenic actions are incompletely understood.
9.2.1.8 Nickel Devices and Prostheses
It has generally been assumed that nickel in stainless steels is
119
biologically inert. However, Ferguson and co-workers have reported
-------
that intramuscular implantation of cylinders of stainless steel (Incoloy--
stainless steel #316--and stainless steel #A-286) in rabbits resulted in
increased nickel concentrations in parenchymal tissues. There is a paucity
of evidence concerning the possible carcinogenicity of implanted nickel
90
alloys in experimental animals. Mitchell et al. found that pellets of
nickel-gallium dental filling material (60 percent nickel and 40 percent
gallium) implanted subdermally in Wistar rats produced local sarcomas in
nine of 10 rats. Local sarcomas developed in five of 10 rats that received
implants of pure nickel. No sarcomas developed in any of 10 other
experimental groups of 10 rats each, which received implants of other
dental materials.
9.2.1.9 Interrelations of Nickel with Polycyclic Aromatic Hydrocarbons
Evidence of carcinogenic synergism between nickel compounds and poly-
cyclic aromatic hydrocarbons has been derived from carcinogenesis studies
94 95
in animals ' and biochemical studies of the effects of nickel compounds
on the metabolism of benzo[a]pyrene. ' ' In a study by Toda,
five of 30 rats that received intratracheal injections of nickel oxide
in combiantion with 20-methylcholanthrene developed pulmonary neoplasms
(squamous cell carcinomas).
95
Maenza et al. reported that the latent period between administration
of carcinogen and development of sarcomas was significantly shorter, by
30 percent, in rats that received intramuscular injections of nickel
sulfide and benzo[a]pyrene than in rats that received only one of the two.
Reduction of the latent period was not achieved by increasing the dosage
of nickel sulfide or benzo[a]pyrene administered singly. Sunderman
-------
demonstrated that exposure of rats to nickel carbonyl by inhalation or
intravenous injection inhibited the induction of benzopyrene hydroxylase
activity in lung and liver. Sunderman and Dixon et al. suggested that
nickel might promote carcinogenesis by inhibiting benzopyrene hydroxylation,
thus prolonging tissue retention of benzo[a]pyrene. Subsequently, Sunderman
121
and Roszel demonstrated that exposure to nickel carbonyl inhibited the
mobilization of benzo[a]pyrene from lung and liver for 48 hours. Furthermore,
122
Kasprzak et al. observed that the incidence of premalignant pathological
reactions in the lungs of rats that received an intratracheal injection of
nickel subsulfide and benzo[a]pyrene was significantly greater than in the
lungs of rats that received only one of the two compounds.
9.2.1.10 Possible Interrelations of Nickel with Parasites
123
Kasprzak et al. have studied the effect of Trichinella spiral is
infection on the induction of sarcomas in rats after intramuscular injection
of nickel sulfide. Administration of T. spiral is larvae in rats
five days before the injection of nickel sulfide significantly increased
the incidence of rhabdomyosarcomas. «
9.2.1.11 Nickel in the Reproductive Process
124
The results of Phatak and Pouwardhan suggest that litter size was
125
reduced in rats fed nickel at 1000 yg/g in the diet. Hoey studied the
acute and chronic effects of nickel sulfate given subcutaneously at 0.04
millimole/kg on testicular development. Shrinkage of central
tubules, hyperemia of intertubular capillaries, and disintegration of
spermatazoa were observed 18 hours after a single dose. Multiple doses
extended the acute effects but all changes proved to be nearly
-------
completely reversible. Inhibition of spermatogenesis has also been
reported after oral administration of daily doses of nickel sulfate at
126
25 mg/kg. After 120 days of dosing, the male rats were apparently
infertile, since no pregnancies resulted when the males were caged with
females in estrus.
Soluble nickel fats given in drinking water also produced adverse
127
effects on reproduction in rats. Nickel administered at 5 nig/liter
continuously over three generations resulted in a reduction in the average
litter size with each succeeding generation and increased mortality of
offspring as compared to controls. The number of runts was increased in
each succeeding generation and fewer males than normal were born by the
third generation.
DRAFT
DO KOT QUOTE Q.UITE-
-------
DRAFT
9.3 VEGETATION -;, jjgr Q
Nickel has not been demonstrated to be essential for proper growth
and development of plants, therefore, the problems associated with plant
growth are due to an overabundance and not a lack of nickel.
Dwarfing or growth repression are the first symptoms of nickel
toxicity. In time, a chlorosis develops similar to the symptoms associated
with iron deficiency. In cereals, the chlorosis appears as white or
light yellow and green striping. In dicotyledonous plants, a mottling
I 00
of the leaf occurs. If toxicity is severe, chlorosis is followed by
death of the plants.
The concentrations of nickel in soil reported as being toxic to
plants range from 0.5 yg/g for buckwheat and 2 yg/g for beans, barley,
128
and oats. The concentration of nickel in the soil is not as important
as its availability to the plant. The available or exchangeable nickel
1 og
content in toxic soils was found to range from 3 yg/g upward. The
high nickel (4000 yg/g maximum) and chromium content of serpentine soils
of southern Rhodesia causes the soil to be highly infertile. The nickel
content of indigenous grasses is closely correlated with the amount of
exchangeable nickel in the soil. Oats grown on a soil with 70 yg/g of
exchangeable nickel developed transverse white banding due to chlorosis
while lucerne exhibited intense yellow chlorosis within two days of
129
emergence and died within forty. The pH of the soil plays an important
part in the availability of nickel to plants. The nickel-calcium ratioi\
has been shown to be important in plant assimilation of nickel. Higher
130
levels of calcium tend to reduce the uptake of nickel.
9-37
-------
DRAFT
. .MAT ncnyi: nr> riTT
: ; ; 1 i.; ;..!•..» I L L ! ' ;./( I L
It has been shown however, that the application of lime does not eliminate
nickel uptake or the occurrence of nickel toxicity symptoms in oats
where available nickel is present in very high concentraitons. Calcium
carbonate was added to soil with 70 yg/g exchangeable nickel increasing
the pH from 5.9 to 8.2. This reduced the nickel content of dried oat
leaves and stems from 233 to 84 yg/g, but did not eliminate the toxic
effects.
Experimentally, nickel (II) ions have inhibited degradative changes
associated with senescence and injury in plants. The breakdown of
chlorophyll, protein, and RNA was inhibited by the treatment of detached
131
rice (oryza sativa) leaves with nickel (II). If degradative processes
in plants are changed, littler breakdown and humus formation from plant
material could be significantly reduced.
9.4 MICROORGANISMS
The accumulation of heavy metals in litter and humus could influence
132
the rate of decomposition as most bacteria are sensitive to them.
Nickel has been shown to be quite toxic to microorganisms in general. '
Nickel (II) inhibits fermentation in yeast cells and also is effective
in the control of fungal infection of grain commonly known as rusts
(Puccinia spp.). ' In addition, nickel (II) causes a narcotic
effect in ciliated protozoans resulting from the reduced availability of
ATP.131
The inhibition of microbial activity in litter as well as in soil
through the addition of sewage sludge or other substances containing
high concentrations of nickel and other metals could influence litter
degradation and plant uptake of minerals as well as biogeochemical
cycling. This problem has not been sufficiently illucidated.
-------
00 NOT QUOTE OR 0
9. 5 MATERIALS
Nickel and nickel compounds and cations have no damaging effects
on materials.
9.5.1 Laboratory
No documented materials effects studies have been reported.
9.5.2. Field
No documented materials effects studies have been reported.
-------
Dp 1CT
9.6 WEATHER, VISIBILITY, AND CLIMATE IVu' Qt/OT£ Oft ClT.£
No information could be found on the effect of nickel on
weather, visibility, and climate. Apparently, the relatively small amounts
of this element that occur in the atmosphere have been of no particular
concern to meteorologists. Nickel is released into the atmosphere from
both natural and man-made sources. It is in dust particles picked up
from, the surface of the earth by the wind, and it is a minor
constituent of the meteor dust that is continuously raining down on
the earth. Wood contains nickel so forest fires are thought to be a
significant_ source. It is conceivable that nickel associated with
particulates could affect the formation of precipitation or perform
a catalytic function in chemical transformations of other air
pollutants, however, its effects are expected to be far outweighed
either by more active elements or by elements present in much larger
amounts. Therefore, natural sources of airborne nickel do not
appear to have any undesirable effect on weather, visibility, and
climate.
Man-made sources can produce significant concentrations of nickel
in the atmosphere. The burning of coal is responsible for much of the
nickel in the atmosphere in urban areas. Other sources are the smoke
from burning wood and leaves, cement dust, and the dusts and mists from
manufacturing.
-------
9.7 LAND RESOURCES I - ^^ ^!-"'
-------
nn
DO NOT QUOTE OR CITE
9.8^ REFERENCES
1. Marcussen, Paul V. Geological Considerations on Nickel Dermititis.
British Journal of Industrial Medicine 17: 65-68, 1960.
2. Cronin, Etain. Contact Dermititis XIII: The Significance of
Nickel Sensitivity in Women. British Journal of Dermatology
84: 96-97, 1971.
3. Calnan, C. D. Nickel Dermititis. British Journal of Dermatology
68: 229-236, 1956.
4. Spruit, D., J. W. H. Mali, and N. De Groot. The Interaction of Nickel
Lens with Human Cadaverous Dermis. Electric Potential, Absorption, Swelling,
J. Invest. Derm. 44_: 103-106, 1965.
4. Epstein, S. Contact Dermititis due to Nickel and Chromate--0bser-
vations on Dermal Delayed (Tuberculin-type) Sensitivity. Archives
of Dermatology 73: 236-255, 1956.
5. Report of the Panel on Nickel of the Committee on Medical and
Biological Effects of Environmental Pollutants, Division of Medical
Sciences, National Research Council, 1974,
6. Armit, H. W. The Toxicology of Nickel Carbonyl. Journal of Hygiene
8: 565-600, 1908.
7. Sunderman, F. W., Sr. Nickel Poisoning, pp. 387-396. In F. W.
Sunderman, and F. W. Sunderman, Jr., Eds. Laboratory Diagnosis of
Diseases Caused by Toxic Agents. St. Louis: Warren H. Green, Inc.
1970.
8. Sunderman, F. W. and F. W. Sunderman, Jr. Nickel Poisoning
VIII. Dithiocarb: A New Therapeutic Agent for Persons Exposed
to Nickel Carbonyl. American Journal of Medical Science 236:
26-31, 1958.
-------
DRAFT TC
DO NOT QUOTE OR CITE
9- Vuopala, U., E. Huhti, J. Takkunen and M. Hiukko. Nickel
Carbonyl Poisoning. Annals of Clinical Research 2: 214-222,
1970.
10. Sunderman, F. W., Jr. The Current Status of Nickel Carcinogenesis.
Annals of Clinical Laboratory Science 3: 156-180, 1973.
11. Morgan, J. G. Some Observations on the Incidence of Respiratory
Cancer in Nickel Workers. British Journal of Industrial Medicine
15: 224-234, 1958.
12.. Doll, R. Cancer of the Lung and Nose in Nickel Workers. British
Journal of Industrial Medicine 15: 217-223, 1958.
13. Doll, R., L. G. Morgan and F. E. Speizer. Cancer of the Lung
and Nasal Sinuses in Nickel Workers. British Journal of Cancer
24: 623-632, 1970.
14. Mastromatteo, E. Nickel: A Review of Its Occupational Health
Aspects. Journal of Occupational Medicine 9: 127-136, 1967.
15. Maenza, R. M., A. M. Pradham and F. W. Sunderman, Jr. Radip
Induction of Sarcomas in Rats by a Combination of Nickel Sulfide
and 3,4-Benzpyrene. Cancer Research 31: 2067-2071, 1971.
1fi Cralley, L. J. Electromotive Phenomenon in Metal and Mineral
Particulate Exposures: Relevance to Exposure to Asbestos and
Occurrence of Cancer. American Industrial Hygiene Association
Journal 32: 653-661, 1971.
-------
WM1
00 NOT QUOTE OR CITE
17. Kasprzak, K. S., L. Marchow and J. Breborowicz. Parasites and
Carcinogenesis. Lancet 2: 106-107, 1971.
18. Treagan, L. and A. Furst. Inhibition of Interferon Synthesis
in Mammalian Cell Cultures After Nickel Treatment. Research
Communications in Chemical Pathology and Pharmacology 1: 395-
402, 1970.
20. Gmelin, C. G. Experiences sur 1'action de la baryte, de la
strontiane, du chrome, du molybdene, du tungstene, du tellure,
de 1'osmium, du platine, de 1'iridium, du rhodium, du palladium,
du nickel, du cobalt, de 1'urane, du cerium, du fer et du
manganese sur Torganisme animal. Bull. Sci. Med. 7: 110-117,
1826.
21. Phatak, S. S. and V. N. Patwardhan. Toxicity of Nickel. J. Sci.
Ind. Res. 9b(3): 70-76, 1950.
22. Phatak, S. S. and V. N. Patwardhan. Toxicity of Nickel «t Accu-
mulation of Nickel in Rats Fed on Nickel-containing diets and
Its Elimination. J. Sci. Ind. Res. llb(5): 173-176, 1952.
23. Schroeder, H. A., J. J. Balassa and W. H. Vinton, Jr. Chromium,
Lead, Cadmium, Nickel and Titanium in Mice. Effect on Mortality,
Tumors and Tissue Levels. J. Nutr. 83: 3, 239-250, 1964.
24. Schroeder, H. A., W. H. Vinton, Jr. and J. J. Balassa. Effect of
Chromium, Cadmium, and Other Trace Metals on the Growth and
Surivval of Mice. J. Nutr. 80: 1, 39-47, 1963.
25. O'Dell, G. D., W. J. Miller, W. A. King, S. L. Moore and D. M.
Blackmon. Nickel Toxicity in the Young Bovine. J. Nutr. 100:
1447-1453, 1970.
-------
UKMM
DO NOT QUOTE OR CITE
26. Weber, C. W. and B. L. Reid. Nickel Toxicity in Growing Chicks.
J. Nutr. 95: 612-616, 1968.
27. Gordynya, R. I. Effect of a Ration Containing a Nickel Salt
Additive on Carbohydrate Metabolism in Experimental Animals.
Vop. Rastion. Pitan. No. 5: 167-170, 1969. (In Russian).
28. Smith, J. C. and B. Hackley. Distribution and Excretion of
Nickel-63 Administered Intravenously to Rats. J. Nutr. 95:
541-546, 1968.
29 Onkelinx, C., J. Becker and F. W. Sunderman, Jr. Compartmental
co
Analysis of the Metabolism of Ni(II)rin Rats and Rabbits. Res,
Commun. Chem. Pathol. Pharmacol. 6: 664-676, 1973.
30. Berenshyteyen and Shifrina
31. Clary, J. J., and L. Vignati. Nickel chloride-induced changes in
Glucose Metabolism in the Rat. In Abstracts of Papers. Society of
Toxicology. Twelfth Annual Meeting, New York, New York, March 18-22,
1973. New York: Academic Press, Inc., 1973.
??. Bingham, E., W. Barkley, M. Zerwas, K. Stemmer and P. Taylor.
Responses of Alveolar Macrophages to Metals. I. Inhalation of
Lead and Nickel. Arch. Environ. Health 25: 406-414, 1972.
-------
DRAFT TP
DO NOT QUOTE OR CITE
''33. Sanders, C., Jackson, T., Adee, R., Powers, G. and Wehner, A.,
Distribution of Inhaled Metal Oxide Particles in Pulmonary Alveoli,
Arch. Intern. Med. 127.: 1085-1089 (June 1971).
34. Rehner, A. P. and Craig, DT K. Toxicology of Inhaled NiO and CoO
in Syrian Golden Hamsters. Am. Ind. Hyg. Assoc. J. 33_:146-155
(March 1972).
35. Report of IRPC Committee II Task Group on Lung Dynamics, Deposition
and Retention Models for Internal Dosimetry of the Human Respiratory
Tract, Health Phys. 12^:173-207 (1966).
36.' Franz, R. D. Toxicitaten einiger Spuremetalle. Naunyn Schmiedeberg
Arch. Exp. Path. 244: 17-20, 1962.
*.v i - «• • -^ - -
37. Nofre, C., J. M. Clement and A. Cier. Toxicite comparee de
quelques ions metalliques et de leur chelate a 1'acide
ethylenediaminetetraacetique. Path. Biol. 11: 853-865, 1963.
38. Joesten, M. D. and R. A. Hill. Toxicity of Metal Complexes
of Octamethylpyrophosphoramide in Water and Dimethylsulfoxide.
J. Agr. Food Chem. 14: 512-514, 1966.
39, Haro, R. T., A. Furst and H. L. Falk. Studies on the Acute Toxicity
of Nickelocene. Proc. West. Pharmacol. Soc. 11: 39-42, 1968.
40, Innes, J. R. M., B. A. Ulland, M. G. Valeric,' L. Petrucelli,
L. Fishbein, E. R. Hart, A. J. Pallotta, R. R. Bates, H. L. Falk,
J. J. Gart, M. Klein, I. Mitchell and J. Peters. Bioassay of
Pesticides and Industrial Chemicals for Tumorigenicity in Mice:
A Preliminary Note. J. Nat. Cancer Inst. 42: 1101-1114, 1969.
41: McKendrick, J. C. and W. Snodgrass. On the Physiological Action
of Carbon Monoxide of Nickel. Proc. Phil. Soc. Glasgow 22:
204-216, 1890-1891. ~ ^
-------
42. Kanriot, M. and C. Richet. Des effets physiologiques et toxiques
du nickel carbonyl. C. R. Soc. Biol. (Series 9): 185-186, 1891.
43: Langlois, P. Action du nickel carbonyl sur le gas du sang.
C. R. Soc. Biol. 3(Ser. 9): 212-213, 1891.
44. Vahlen, E. Ueber das Verhalten des Kohlenoxydnickels im \1"
Thierkorper. Arch. Exper. Path. Pharm. 48: 117-133, 1902. '«.'"
45. Armit, H. W. The Toxicology of Nickel Carbonyl. Part II. ^ ,?~
<2\ ^
J. Hyg. 8: 565-600, 1908. <*\
^JJ
46. Garland, G. An Investigation of the Comparative Toxic Effects of ^
Nickel Carbonyl and Carbon Monoxide on a Closely Inbred Stock ^
of Mice. M. A. Thesis. University of Maine, Orono, Maine, 1933.
47 pp.
47- Barnes, J. M. and F. A. Denz. The Effect of 2-3 Demercapto-
propanol (BAL) on Experimental Nickel Carbonyl Poisoning.
Brit. J. Ind. Med. 8: 117-126, 1951.
48. Kincaid, J. F., J. S. Strong, and F. W. Sunderman. Nickel
Poisoning. I. Experimental Study of the Effects of Acute and
Subacute Exposure to Nickel Carbonyl. Arch. Ind. Hyg. 8: 48-
60, 1953.
49.. Sanotskii, I. V. Action Mechanism of Nickel Carbonyl. Farmakol.
Toksikol. 18(2): 48-50, 1955. (In Russian).
50.. Ghiringhelli, L. Utilizzazione del B. A. L. e dell'acido
tiotico nella terapia dell avvelenamento da nichelcarbonile.
Atti Soc. Lomb. Med. Biol. 12: 24-26, 1957.
-------
51. West, B. and F. W. Sunderman. Nickel Poisoning. VII. The
Therapeutic Effectiveness of Alkyl Dithiocarbamates in Experimental
Animals Exposed to Nickel Carbonyl. Amer. J. Med. Sci. 236:
15-25, 1958.
52 • Sunderman, F. W., C. L. Range, F. W. Sunderman, Jr., A. J. Donnelly
and G. W. Lucyszn. Nickel Poisoning. XII. Metabolic and
Pathologic Changes in Acute Pneumonitis from Nickel Carbonyl.
Amer. J. Clin. Path. 36: 477-491, 1961.
53_ Sunderman, F. W. Nickel and Copper-mobilization by Sodium
Diethyldithiocarbamate. J. New Drugs 4: 154-161, 1964.
5~4". Hackett, 3. L. and F. W. Sunderman, Jr. Acute Pathological
Reactions to Administration of Nickel Carbonyl. Arch. Environ.
Health 14: 604-613, 1967.
55. Sanina, lu. P. Toxicology of Nickel Carbonyl. Farmakol.
Toksikol. 18(2): 144-148, 1965.
56. Hackett, ii. L. and F. W. Sunderman, Jr. Pulmonary Alveolar
Reaction to Nickel Carbonyl. Ultrastructural and Histochemical -
Studies. Arch. Environ. Health 16: 349-362, 1968.
57.. Hackett, R. L. and F. W. Sunderman, Jr. Nickel Carbonyl. Effects
Upon the Ultrastructure of Hepatic Parenchymal Cells. Arch.
Environ. Health 19: 337-343, 1969.
58. Gilman, J. P. W., M. R. Daniel and P. K. Basrur. Observations
on Tissue Selectivity in Nickel Tumorigenesis. Prc. Amer.
Assoc. Cancer Res. 7: 24, 1966.
59- Sunderman, F. W., Jr. and C. E. Selin. The Metabolism of Nickel-63
Carbonyl. Toxicol. Appl. Pharmacol. 12: 207-218, 1968.
6.0. Sunderman, F. W., Jr., iN. 0. Roszel and R. J. Clark. Gas
Chromatography of Nickel Carbonyl in Blood and Breath. Arch.
Environ. Health 16: 836-843, 1968. ^ ' lt?
-------
61. Sunderman, F. W..,, Jr. Inhibition of Induction of Benzpyrene
Hydroxylase by Nickel Carbonyl. Cancer Res. 27^:950-955, 1967.
62. Sunderman, F. W., Jr. Nickel Carbonyl Inhibition of Cortisone
Induction of Hepatic Tryptophan Pyrrolase. Cancer Res. 27:
1595-1599, 1967.
63. Sunderman, F. W., Jr. Nickel Carbonyl Inhibition of Pheno-
barbital Induction of Hepatic Cytochrome P-450. Cancer Res. 28:
465-470, 1968.
64. Sunderman, F. W., Jr. and M. Esfahani. Nickel Carbonyl Inhibition
of RNA Polymerase Activity in Hepatic Nuclei. Cancer Res. 28:
2565-2567, 1968.
65. Beach, D. J. and F. W. Sunderman, Jr. Nickel Carbonyl Inhibition
of C-orotic Acid Incorporation into Rat Liver RNA. Proc. Soc.
Exp. Biol. Med. 131: 321-322, 1969.
66. Beach, D. J. and F. W. Sunderman, Jr. Nickel Carbonyl Inhibition
of RNA Synthesis by a Chromatin-RNA Polymerase Complex from
Hepatic Nuclei. Cancer Res. 30: 48-50, 1970.
57.. Sunderman, F. W., Jr. and K. C. Leibman. Nickel Carbonyl
Inhibition of Induction of Aminopyrine Demethylase Activity in
Liver and Lung. Cancer Res. 30: 1645-1650, 1970.
68. Sunderman, F. W., Jr. Effect of Nickel Carbonyl Upon Hepatic
Concentrations of Adenosine Triphosphate. Res. Commun. Chem.
Path. Pharmacol. 2: 545-551, 1971.
-------
UKftN
DO HOT QUOTE OR CITE
69. Witschi, H. A Comparative Study of In Vivo RNA and Protein
Synthesis in Rat Liver and Lung. Cancer Res. 32: 1686-1694, 1972.
2+ I
70. Fedorchenko, 0. Ya. and L. M. Petrun. Effect of Ni Ion's on the
Dephosphorylation of ATP and Formation of Ami no Acyl Phosphates
by Enzymes of Rat Liver Microsomes in the Presence of Amino Acids.
Ukr. Biokhim. Zh. 41: 680-685, 1969. (In Russian - Summary in English).
i
71. Raff, E. C. and J. J. Blum. Some Properties of a Model Assay
for Ciliary Contractibility. J. Cell. Biol. 42:,831-834, 1969.
72. Mustafa, M. G., C. E. Cross, R. J. Munn and J. A. Hardie. Effects
of Divalent Metal Ions on Alveolar Macrophage Membrane Adenosine
Triphosphatase Activity. J. Lab. Clin. Med, 77: 563-571, 1971.
73. JQO, F. Changes in the Molecular Organization of the Basement
Membrane After Inhibition of Adenosine Triphosphatase Activity
in the Rat Brain Capillaries. Cytobios 3: 298-301, 1969.
74• Joo, F. Effect of Inhibition of Adenosine Triphosphatase
Activity on the Fine Structural Organization of the Brain
Capillaries. Nature 219: 1378-1379, 1968.
75. Sigel, H., K. Becker and D. B. McCormick. Ternary Complexes
in Solution. Influence of 2,2'-bipyridyl on the Stability of
1:1 Complexes of C02+, Ni2+, Cu2"1" and Zn2+ with Hydrogen Phosphate
Adenosine 5'-monophosphate, and Adenosine 5'-triphosphate.
Biochim. Biophys. Acta 148: 655-664, 1967.
76. Nilzen, A. and K. Wikstrom. The Influence of Lauryl Sulphate
on the Sensitization of Guinea Pigs to Chrome and Nickel. Acta.
Derm. Venereol. 35: 292-299, 1955.
77. Stewart, S. G. and F. E. Cromia. Experimental Nickel Dermatitis.
J. Allergy 5: 575-582, 1934.
-------
DRAFT
L;0 NOT QUOTE 0.1 ,r,l
78. Walthard, B. Die Erzeugung Experimenteller Nickelidiosynkrasie
bei Laboratorium-stieren. Schweiz. Med. Wochenschr. 7: 603-604,
1926.
79. Samitz, M. H. and H. Pomerantz. Studies of the Effects on the Skin
of Nickel and Chromium Salts. A.M.A. Arch. Ind. Health 18: 473-
479, 1958.
80. Hutchinson, F., E. J. Raffle and T. M. MacLeod. The Specificity
of Lymphocyte Transformation In Vitro by Nickel Salts in Nickel
Sensitive Subjects. J. Invest. Derm. 58: 362-365, 1972.
81. Forman, L. and S. Alexander. Nickel Antibodies. Brit. J. Derm.
87: 320-326, 1972.
^- Macleod, T. M., F. Hutchinson and E. J. Raffle. The Uptake of
Labelled Thymidine by Leucocytes of Nickel Sensitive Patients.
Brit. J. Derm. 82: 487-492, 1970.
83. Grosfeld, J. C. M., A. J. M. Penders, R. deGrood and L. Verwilghen.
In Vitro Investigations of Chromium- and Nickel-hypersensitivity
with Culture of Skin and Peripheral Lymphocytes. Dermato!ogica
132: 189-198, 1966.
84-. Pappas, A., C. E. Orfanos and R. Bertram. Non-specific Lymphocyte
Transformation In Vitro by Nickel Acetate. A Possible Source of
Errors in Lymphocyte Transformation Test (LTT). J. Invest. Derm.
55: 198-200, 1970.
85. Sunderman, F. W., Jr. The Current Status of Nickel
Carcinogenesis. Ann. Clin. Lab. Sci. 3:156-180, 1973.
-------
DRAFT rr
r»^Tc nR CITE
86. Heath, J. C. and M. R. Daniel. The Production of Malignant Tumours
by Nickel in the Rat. Brit. J. Cancer 18: 261-264, 1964.
«7. Heath, J. C. and M. Webb. Content and Intracellular Distribution
of the Inducing Metal in the Primary Rhabdomyosarcomata Induced
in the Rat.
88 - Hueper, W. C. Experimental Studies in Metal Cancerigenesis. I.
Nickel Cancer in Rats. Texas Rep. Biol. Med. 10: 167-186, 1952.
89. Hueper, W. C. Experimental Studies in Metal Cancerigenesis. IV.
Cancer Produced by Parenterally Induced Metallic Nickel. J.
Nat. Cancer Inst. 16: 55-67, 1955.
90. Mitchell, D. F., G. B. Shankwalker and S. Shazer. Determining
the Tumorigenicity of Dental Materials. J. Dent. Res. 39:
1023-1028, 1960.
91. Hueper, W. C. Experimental Studies in Metal Cancerigenesis. IX.
Pulmonary Lesions in Guinea Pigs and Rats Exposed to Prolonged
Inhalation of Powdered Metallic Nickel. A.M.A. Arch. Path.
65: 600-607, 1958.
92. Sunderman, F. W., A. J. Donnelly, B. West and J. F. Kincaid.
Nickel Poisoning. IX. Carcinogenesis in Rats Exposed to Nickel
Carbonyl. A.M.A. Arch. Ind. Health 20: 36-41, 1959.
~$3.. Lau, T. C., R. L. Hackett and F. W. Sunderman, Jr. The Carcinogenicity
of Intravenous Nickel Carbonyl in Rats. Cancer Res. 32: 2253-2258,
1972.
94. Toda, M. Experimental Studies of Occupational Lung Cancer. Bull.
Tokyo Med. Dent. Univ. 9: 440-441, 1962.
-------
95. Maenza, R. M., A. M. Pradhan and F. VI. Sunderman, Jr. Rapid
Induction of Sarcomas in Rats by a Combination of Nickel Sulfide
and 3,4-benzpyrene. Cancer Res. 31: 2067-2071, 1971.
96. Sunderman, F. W., Jr., T. J. Lau and L.-J. Cralley. Inhibitory
Effect of Manganese Upon Muscle Tumorigenesis by Nickel Sulfide.
Proc. Amer. Assoc. Cancer Res. 14: 24, 1973.
.97. Oilman, J. P. W. and G. M. Ruckerbauer. Metal Carcinogenesis.
I. Observations on the Carcinogenicity of a Refinery Dust, Cobalt
Oxide, and Colloidal Thorium Dioxide. Cancer Res. 22: 152-157,
1962.
"98. Friedman, I. and E. S. Bird. Electron Microscope Investigation
of Experimental Rhabdomyosarcoma. J. Path. 97: 375-382, 1969.
99. Webb, M., J. C. Heath, and T. Hopkins. Intramuscular Distribution of
the Inducing Metal in Primary Rhabdomyosarcomata induced by the Rat
by Nickel, Cobalt and Cadmium. Brit. J. Cancer 26.: 274-278, 1972.
100. Karvanik, 1964.
101. Kasprzak, K. S. and F. W. Sunderman, Jr. The Metabolism of Nickel
Carbonyl- C. Toxicol. Appl. Pharmacol. 15: 295-303, 1969.
102. Buu-Hoi, N. P., D-P. Hieu. Effects Des Metallocenes Sur la
Metabolisation Des Certains Medicaments Chez le Rat. C. R. Acad.
Sci. (D) 27£:217-219, 1970.
-------
,,-rc
r,0 HOT QUOTE OR CITE
103. Singh, A. and J. P. W. Gilman. Use of the Double Diffusion Chamber
for an Analysis of Musle-Nickel Sulfide Interaction. Indian. J. Med.
Res. 61:704-707, 1973, i
104. Heath, J. C., M. Webb, and M. Caffrey. The Interaction of Carcinogenic
Metals with Tissues and Body Fluids. Cobalt and Horse Serum.
Brit. J. Cancer 23_: 153-166, 1969.
105. Webb, M., J. C. Heath, and T. Hopkins. Intramuscular Distribution of
the (Inducing Metal in Primary Rhabdomyosarcomata Induced in the Rat by
Nickel, Cobalt and Cadmium. Brit. J. Cancer 26_j_274-278, 1972.
CO Ox
106. Webb, M., and S. M. Weinzierl. Uptake of Ni from its Complexes
w\th Proteins and Other Ligands by Mouse Dermal Fibroplasts JJT_
vitro. Brit. J. Cancer. 26_: 292-298, 1972.
107. Weir, H. M., and W. A. Myers. Liquid fuels, p. 2349. In J. H'.
Perry, Ed." Chemical Engineer's Handbook. New York: McGraw-
Hill Book Co., Inc., 1.941.
108. Weinzierl, S. M. and M. Webb. Interaction of Carcinogenic Metals
with Tissue and Body Fluids. Brit. J. Cancer 2^6:279-291, 1972.
109. Webb, M. and S. M. Weinzierl. Uptake of Ni from its. Complexes
with Proteins and Other Ligands by Mouse Dermal Fibroplasts jj^
vitro. Brit. J. Cancer. 26T292-298, 1972.
110. Sunderman, F. W., Jr. Measurements of Nickel in Biological
Materials by Atomic Absorption Spectrometry. Amer. J. Clin. Path.
44:182-188, 1965.
a, :."••*
-------
oDRAFT
DO MOT GUC7E OR CITE
111. Sunderman, F. W., Ji?. Effect of Nickel Carbonyl Upon Incorporation
14
of C-leucine into Hepatic Microsomal Proteins. Res. Commun.
Chem. PQath. Pharmacol. 1:161-168, 1970.-
112. Treagan, L., and A. Furst. Inhibition of Interferon Synthesis in
Mammalian Cell Cultures After Nickel Treatment. Res. Commun.
Chem. Path. Pharmacol. 1:395-402, 1970.
113. Basrur, P. K. and J. P. W. Gilman. Morphologic and Synthetic
Response of Normal and Tumor Muscle Cultures to Nickel Sulfide.
Cancer Res. 27: 1168-1177, 1967.
114. Swierenga, S. H. H., and P. K. Basrur. Effect of Nickel on
Cultured Rat Embryo Muscle Cells. Lab. Invest. 19:663-674, 1968.
115. Furst, A. Trace Elements Related to Specific Chronic Diseases:
Cancer, pp. 109-130. In H. L. Cannon, and H. C. Hopps, EDs.
Environmental Geochemistry in Health and Disease. American
Association for Advancement of Science Symposium, Dal Is, Texas,
December 1968. The Geological"Society of America Memoir No. 123.
Boulder, Col: The Geological Society of America, Inc., 1971.
116. Furst, A., and R. T. Haro. A Survey of Metal Carcinogenesis.
Prog. Exp. Tumor Res. 12_:102-133, 1969.
117. Furst, A., and R. T. Haro. Possible Mechanism of Metal Ion
Carcinogenesis, pp. 310-320. In E.' D. Bergfnann, and P. Pullman, Eds.
0
Quantum Aspects of Heterocyclic Compounds in Chemistry and Biochemistry.
Proceedings of the International Symposium Held in Jerusalem,
31 March - 4 April 1969, Jerusalem, Israel. Jerusalem: Israel
Academy of Sciences and Humanities, 1970.
-------
DRAFT
'!.;;vr UiOa Oii CITE.
I
118. Williams, D. R. Metals, ligands, and Cancer. Chem. Rev. 7^:202-213,
1972.
119. Ferguson, A. B., Jr.:, Y. Akohoshi, P. G. Laing, arid E. S. Hodge.
Characteristics of Trace Ions Released from Embedded Metal
Implants in the Rabbit. J. Bone Joint Surg. 44A_:323-336, 1962.
120. Dixon, J. R., D. B. Lowe, D. E. Richards, L. J. Cralley, and H. E.
!
Stokinger. The Role of Trace Metals in Chemical Carcinogenesis:
Asbestos Cancer. Cancer Res. 3£: 1068-1074, 1970.
121. Sunderman, F. W., Jr., and N. 0. Roszel. Effect of Nickel Carbonyl
Upon the Detoxification and Mobilization of 3,4-benzpyrene. Amer.
J. Clin. Pathol. 49_:240, 1968.
122. Kasprzak, K. S., L. Marchow, and J. Breborowica. Pathological
Reactions in Rat Lungs Following Intratracheal Injection of Nickel
Subsulfide and 3,4-benzpyrene. Res. Commun. Chem. Path. Pharmacol.
6^:237-246, 1973.
123. Kasprzak, K. S., L. Marchow, and J. Breborowicz. Parasites and
Carcinogenesis. Lancet 2;106-107, 1971.
124. Phatak, S. S. arid V. N. Patwardhan. Toxicity of Nickel. J. Sci.
Ind. Res. 9b(3):70-76, 1950.
125. Hoey, M. J. The Effects of Metallic Salts on the Histology and
Functioning of the Rat Testis. J. Reprod. Ferr. 1_2:461-471, 1966.
126. Von Waltschewa, W., M. Slatema, and Iw. Michailow. Hodenveranderungen
bei Weissen Ratten durch Chronische Verabreichung von Nickelsulfat.
Exp. Path. Bd. 6.: 116-120, 1972.
-------
„
;• j HQT QUOTE OR CI
127. Schroeder, H. A., and"M. Mitchner. Toxic Effects of Trace Elements'
on the Reproduction of Mice and Rats. Arch. Environ. Health 23_: 102-106,
1971.
128., Vanselow, Albert P. Nickel in Diagnostic Criteria for Plants and
Soils. Riverside, Calif. H.D. Chapman-(ed.) 1966.
129. Soane, B. D., and D. H. Saunder. Nickel and Chromium Toxicity of
I
Serpentine Soils in Southern Rhodesia. Soil Sci. 88(6):322-330
(1959).
130. Severne, B. C. Nickel Accumulation by Hybanthus floribundus.
Nature 248: 807-808, 1974.
131. Preliminary Investigation of Effects on The Environment of Boron,
Indium, Nickel, Selenium, Tin, Vanadium and Their Compounds. Vol. Ill
Nickel. Prepared for Office of Hazardous Materials. Control
of the U. S. Environmental Protection Agency under Contract No.
68-01-2215. June, 1974.
132. Tyler, G. Heavy Metals Pollute Nature, May Reduce Productivity.
Ambio. 1_: 52-59, 1972.
133. Bowefi, H. J. M. Trace Elements in Biochemistry. Academic Press.
London. 1966, 241 p.
134. Antonovics, J., A. D. Bradshaw and R. G. Turner. Adv. in Ecological
Research. 7: 2-85. Academic Press, London. 1971.
-------
, ,;v;Q;:; OR CITE
135. Forsyth, F. R. Inhibition by Nickel of the Respiration and
Development of Established Infections on Thatcher Wheat Caused
Recondita Rob ex Desm. Canadian Journ. Bot. 4_0(3): 415-423 (1962).
136. Forsyth, F. R., and B. Peturson. Control of Leaf Rust of Wheat
with Inorganic Nickel. Plant Dis. Reporter. 43(l):5-8 (1959).
137. Forsyth, F. R., and B. Peturson. Control of Lead and Stem Rust
of Wheat by Zineb and Inorganic Nickel Salts. Plant Dis. Reporter.
44(3):208-311 (1960).
138 Page, A. L. Fate and Effects of Trace Elements in Sewage Sludge
When Applied to Agricultural Lands, A Literature Review Study.
Dept. of Soil Sci. and Agr. Eng., University of California,
Riverside, Calif. 1974. 108 p.
-------
DO NOT QUOTE OR CITE
10. CONTROL TECHNOLOGY AND REMEDIAL ACTIONS
10.1 STATIONARY SOURCES «
10.1.1 Air
Control of nickel emissions from stationary sources is largely
dependent upon the degree of particulate control attainable. The
gaseous nickelcarbonylemitted in some processes is highly toxic but
easily controlled by thermal decomposition above 60°C. Therefore, the
emission of nickel to the atmosphere can be controlled with adequate parti-
culate control devices. The ore processing emissions can be controlled
with present technology such as fabric filters. The clean-up of metallurgical
fumes is a much tougher problem because the preponderance of material.
is less than 5 ym in diameter with up to 80 percent less than 1 ym.
Electrostatic precipitators have been applied with good overall mass
efficiency but data has confirmed theoretical predictions that a drop is
noted in collection of 0.5 ym to 1.0 ym particles (Figure 1) which exist
in such large numbers in metallurgical processes. Baghouses have been
successfully applied to such processes but extensive cooling is required
before the gases can be handled. Though scrubbers are generally considered
to lose significant collection capability below 1 ym, a recently developed
high energy scrubber has been extremely successful in controlling metal
fume from blast furnaces (Figure 2) and electric furnace steel production.
This unit needs large amounts of waste heat to be economically feasible,
but most metallurgical processes have such supplies of untrapped energy.
Some methods have been explored to remove metals from the oil
during refining and this offers the major hope of reducing nickel
Jo-I
-------
Figure 1. Efficiency of Electrostatic Precipitator on a Coal Fired Power Boiler
. o particle size, ym
r
0>
-------
0.01
O.I
o
~2
T"}
5
10
UJ
m 50
90
99
99.9
99.99
0 DIFFUSION BATTERIES/CONDENSATION NUCLEI COUNTER
O OPTICAL SINGLE PARTICLE COUNTER
+ IMPACTOR
j u
i i
i i i i i
99.9
99
95
90
50
o
UJ
o
UJ
(J NJ
UJ I
o
o
10
5
O.I
0.01
0.01 O.I 1.0 10.0
PARTICLE DIAMETER, ^m
Figure 2. Fractional Efficiency of the Lone Star Steel Steam-Hydro Scrubber.
-------
oc MOT'QUOTE OR CITE
emissions from residential combustion.
Reductions of nickel emissions are dependent upon the control
of the particulate emission at the specific source. Mining, metal-
lurgical, and product sources can probably be highly controlled with
proper installation of control devices. Control of combustion sources
is less optimistic due to the size of the nickel containing particulate
and the anticipated degree of control needed to meet emission standards
based on total particulate.
-------
DRAFT
DONOTOUOTtOR
I0:i.2 Solid Waste °
Land disposal has been, historically, the predominant method of
removing solid waste from view, but it is not necessarily the best
disposal method from an environmental standpoint. A landfill does
represent a potential stationary source of nickel contamination,
especially if industrial liquid and sludge wastes are incorporated
into the site.
Detailed planning and the application of sound engineering,
geological, hydrological, meterological, chemical, and biological
techniques to all stages of planning, design, construction, operation
and final site utilization have helped reduce the number and
magnitude of many of the environmental impacts of land disposal
procedures. Control technology involves all of the aforementioned;
specifically, however, proper site selection, liners, tertiary
treatment of liquids, and encapsulation procedures represent modern
procedures to prevent contamination.
Recently, some states have initiated regulations that
landfills must have some kind of impermeable membrane at the bottom
of the fill. In addition, a few require that some system of leachate
collection be installed for treatment. The liners include
several feet of clayey soils, organic polymer material, or several
lifts of asphalt several inches thick. This is an added economic
burden the landfill operator must assume, but it is small when
considering the potential ground water intrusion from leachate
contaminated with toxic materials.
-------
DRAFT
DO NOT QUOTE OP. CITE
Presently, the EPA is investigating the process of
encapsulating hazardous materials prior to placement in landfills.
%
This is still in the experimental laboratory phase but preliminary
results hold forth hope that this may be a viable process.
Another control procedure for protecting against toxic
materials transport in a landfill is tertiary treatment followed
by sludge concentration and isolation. This allows for the handling
of smaller volumes of material so that sound isolation procedures
may be utilized, perhaps encapsulation in the future.
The prime factor involved in all solid waste control technoloav still
remains proper site selection. Without this even the best operated
landfills may eventually fail due to circumstances beyond the control
of the operator. Some considerations are: local springs fed from
underground supplies, fissures in the limestone area, depth of
ground water supply, and local terrain.
When considering landfilling solid waste, it is advisable
to consider it a potential stationary source of many pollutants, and
institute proper preventative measures.
-------
10.3 REFERENCES
1. Particulate Pollutant System Study: Vol. II - Fine Particulate
Emissions. U.S. Environmental Protection Agency, Research Triangle
Park, N. C. Publication Number APTD 0744. August, 1971. p.
> 1
------- |