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

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                           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

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                         DRAFT
   NERC/Cinn      "~  '    V^'Tt Ctt CITE
Albert J. Klee

Gordon Roebeck


    OAQPS

 John Bachman

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                                   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

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                                               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

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                                                         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

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                             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

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                                      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.

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                          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.

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                                                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.

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                               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.

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                                          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

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                                 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.

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                                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.

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                                     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

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                                                           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

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                                           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

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                                  *•"» 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

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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

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         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

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                                        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

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                                                   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

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                                       /--..-•.  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

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                                        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

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          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

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                                            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

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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

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                                          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.

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 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

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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

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                                 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.

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                                         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!

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                                      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

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                                                    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

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                         \            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.

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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

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            DRAFT
     J» WOT QUOTE-OR CITE
F1 g.. ,,5; 1 •  Tto cydtaf of mkroekmenu.

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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.

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                                                 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.

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                                          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.

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                                   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

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                                           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

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                                              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.

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                                           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   .

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                                        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.

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                                                           .      .
                                           *-* 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.

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 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\

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                                           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*

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                                                      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.

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                                                    •       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

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                                                         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.

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                                                 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

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                                          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).

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                            ;: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

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                                               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.

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                                            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

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                                                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.

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                                                           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.

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                                                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

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                                           ^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.

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                                                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.

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                       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

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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.

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    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

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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
                                         .?'•

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                       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

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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.

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                                             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

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                                                      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

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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
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                                              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

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                                               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.
                                     &-'/

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                                                           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.  '

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 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.

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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.

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                                             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.

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                                              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

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                                                  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^

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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-

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                                                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,

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                                                   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.

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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.

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                                         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

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                                   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-*

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                      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-'

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 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.

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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

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                                             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.

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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

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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

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         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.  '  '

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                                                   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

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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.

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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

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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

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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

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     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

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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.

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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.

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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.

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     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

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17.  Rao, M. S. N.,and H
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25.  Lenz, C. R.  and A.  E.  Martell.   Metal Complexes of Carnosine.
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34.  Vohra, P., G.  A.  Gray^and F.  H.  Kratzer.   Phytic Acid-metal
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43.  Palmer, J. D. Sulphate of Nickel  in  Neuralgia.  Richmond
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53.  Weissbach, A.,  B.  L.  Horecker.and J. Hurwitz.  The Enzymatic
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71.  Khodorov, B.  I.  and V.  I.  Belyayev.   Changes  in the Critical
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                                          ++
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79.  Benoit, P. R, and J. Mambrini.   Modification  of  Transmitter
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                                     , —>

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87.  Alonzo, C.  A..and S.  Pell.   A  Study  of Trace  Metals in Myocardial
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101.  Horah, E., and F. W.  Sunderman, Jr.   Fecal Nickel Excretion by
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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.

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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.

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                       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.

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              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.

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            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

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     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.

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9.1.3  Carcinogens Is                                UKAr  I
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     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      •

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                       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

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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.          :

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                                                         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

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      Table 9.2.
TOXICITY OF  INORGANIC NICKEL COMPCu!
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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

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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

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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.

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         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

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 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.

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.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
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                    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.

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                            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

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         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

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                                             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

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             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

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                                                        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

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                                            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

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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

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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

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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.
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                                           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

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                                                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.

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                                        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.

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                                                            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.

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9.7  LAND RESOURCES                   I -  ^^ ^!-"'
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                                                                     nn
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9.8^  REFERENCES
1.  Marcussen, Paul  V.   Geological  Considerations on Nickel Dermititis.
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2.  Cronin, Etain.  Contact Dermititis  XIII:  The Significance of
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3.  Calnan, C. D.  Nickel Dermititis.   British  Journal  of Dermatology
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 4.   Spruit,  D.,  J.  W.  H.  Mali, and N.  De Groot.  The  Interaction of Nickel
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4.  Epstein,  S.   Contact Dermititis due to  Nickel and  Chromate--0bser-
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5.  Report of the Panel on Nickel  of the Committee  on  Medical  and
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7.  Sunderman, F. W., Sr.  Nickel  Poisoning,  pp.  387-396.   In  F. W.
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    26-31, 1958.

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                                                          DRAFT      TC
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  9-  Vuopala, U., E. Huhti, J. Takkunen and M.  Hiukko.   Nickel
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10.   Sunderman, F. W., Jr.  The Current Status  of Nickel Carcinogenesis.
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12..   Doll, R.  Cancer of the Lung and Nose in Nickel Workers.  British
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1fi    Cralley, L. J.  Electromotive Phenomenon in Metal  and Mineral
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      Journal 32: 653-661, 1971.

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                                                         WM1
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20.  Gmelin, C. G.  Experiences sur 1'action de la baryte, de la
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23.  Schroeder, H. A.,  J. J.  Balassa  and  W. H. Vinton, Jr.  Chromium,
     Lead,  Cadmium, Nickel and Titanium in Mice.  Effect on Mortality,
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24.  Schroeder, H. A.,  W. H.  Vinton,  Jr.  and J. J. Balassa.  Effect of
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     1447-1453, 1970.

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                                                         UKMM
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26.  Weber, C. W. and B.  L.  Reid.   Nickel Toxicity in Growing Chicks.
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27.  Gordynya, R. I.   Effect of a  Ration Containing a Nickel Salt
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28.  Smith,  J. C. and B. Hackley.   Distribution and  Excretion of
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 29  Onkelinx, C., J. Becker and F. W. Sunderman,  Jr.   Compartmental
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     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
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 ??.   Bingham,  E., W.  Barkley, M. Zerwas, K. Stemmer and P.  Taylor.
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''33.   Sanders, C., Jackson, T., Adee, R., Powers, G. and Wehner, A.,
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  34.   Rehner, A. P. and Craig, DT K.  Toxicology of Inhaled NiO and CoO
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  35.   Report of IRPC Committee II Task Group on Lung Dynamics,  Deposition
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 36.'  Franz, R.  D.   Toxicitaten  einiger Spuremetalle.  Naunyn Schmiedeberg
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                                                *.v  i - «• •  -^ - -
 37.  Nofre, C.,  J.  M.  Clement  and  A. Cier.  Toxicite  comparee de
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 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
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 40,  Innes, J. R. M.,  B. A.  Ulland,  M.  G.  Valeric,' L. Petrucelli,
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 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.              ~  ^

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 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.

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 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?

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 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.

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                                                  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
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76.  Nilzen, A. and K. Wikstrom.  The Influence of Lauryl  Sulphate
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77.  Stewart,  S. G. and F. E. Cromia.  Experimental  Nickel Dermatitis.
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                                                DRAFT
                                       L;0 NOT QUOTE  0.1  ,r,l
 78. Walthard, B.  Die Erzeugung Experimenteller Nickelidiosynkrasie
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 79. Samitz, M. H. and H. Pomerantz.   Studies  of the  Effects  on the Skin
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 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.

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                                                    DRAFT      rr
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  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.

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   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.

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                                                          ,,-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, :."••*

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                                               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.

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                               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.

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                                                „
                           ;• 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.

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                                , ,;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.

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                                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

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      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.

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                                                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.

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                                                        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.

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                                                      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.

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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

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