Environmental
Consultants, Inc.
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ADDENDUM TO THE
HEALTH ASSESSMENT DOCUMENT
FOR CHROMIUM
DRAFT
NOVEMBER 1986
EPA/ECAO
Prepared By:
James M. Kawecki
Susan Barlow
TRC Environmental Consultants, Inc.
EPA Conctract 68-02-3886, Task 44
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OVERVIEW AND INTERPRETIVE SUMMARY AND CONCLUSION
Approximately 175 new references were reviewed for consideration in this
addendum to the 1984 Health Assessment Document for Chromium. Many of the
references were published since the completion of' the 1984 HAD; others were
not included in the 1984 document. The purpose of this addendum was to
address several technical issues which remained still unresolved after the
last document. In addressing these issues, the material previously used for
the 1984 document was reviewed and cited, when appropriate. As such, this
current report cannot stand alone; it is simply an addendum to the 1984 HAD
which addresses the following issues:
• Oxidation states and persistence of these states in the
environment.
• Sampling and analytical methodology to differentiate these
oxidation states and amounts at the submicrogram level.
• Degree of exposure to chromium in the environment - acute and
chronic.
• Effects from environmentally relevant levels and the respiratory
tract irritation, obstructive lung disease and pneumoconiosis.
These issues are addressed in this section of the addendum. The remaining
material can be used to supplement this discussion.
Chromium Oxidation States and their Persistence in the Environment
The most chemically stable state for chromium is chromium III, which
comprises most of the total chromium in the environment. Chromium VI is
readily reduced into Cr(IJI) in the presence of organic material and
particularly at lower pH levels to form stable Cr(III) complexes. Under
certain conditions, Cr(III) will oxidize the Cr(VI). The important variable
in this reaction is the presence of manganese oxide, which is reduced as
-11-
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Cr(III) is oxidized. Recent theoretical work of Rai (1986), Bartelett (1986)
and others have focused on reaction-rate kinetics for environmental chromium,
but the relative abundances of chromium valence states in the ambient
environment are still not well characterized. The oxidation state of chromium
in the ambient air most likely depends on the proximity to sources that emit
one form over the other, or mixtures of both. Since Cr(III) is found
naturally in the earth's crust, in areas that are not source dominated, most
of the airborne chromium is probably of the trivalent state. Additional
research is needed to develop quantitative data and mathematical descriptions
for predicting the chemical attenuation of chromium in the environment. For
now, however, the available data indicate that under "typical" environmental
conditions (unless there are nearby sources of Cr(VI)), which would include a
slightly acidic environment, chromium exists primarily as Cr(III). Also, from
limited research, it appears that Cr(VI) exists primarily in the fine particle
phase, where for some source specific locations it accounted for about 35% of
the total mass and 85% of the mass below 10 urn.
Sampling and Analytical Methodology for Each Oxidation State at Relatively Low
Levels
Several methods are available to measure total chromium at the ppb level.
Routine monitoring methods to speciate chromium oxidation states (Cr(III) and
Cr(VI)) at ambient air levels (less"the 1 ppb) are not available. Several
research methods are under development which may be amenable for routine
monitoring of Cr(VI). Some of the more prominent problems with the existing
methods include the following:
1) interference in the sampling and collection procedure and of the
presence of other atmospheric contaminants;
2) losses during sample pretreatment;
3) oxidation/reduction of the sampling during analysis.
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Some comparative studies are presented in the analytical section of this
addendum on ways to mitigate these problems, but at the expense of accuracy
and sensitivity. In general, the methods used routinely to monitor total
chromium in ambient air, such as neutron activation analyses, a
t
non-destructive technique, are accurate and sensitive to relatively low total
chromium levels (sub ug/m3). Pre-treatment of the sample or using other
collection methods to determine oxidation state Cr(III)/Cr(VI) lack the
sensitivity to measure these species at the levels found commonly in ambient
air.
Degree of Exposure to Chromium in the Environment
Little new information was found on the types of chromium and compounds
occurring in the environment. While analytical methods are available for
differentiating Cr(III) from Cr(VI) in occupational settings they are not
sufficiently sensitive for ambient air monitoring. Accordingly, knowledge
about the forms of chromium emitted and the transport, transformation, and
persistence of these species is the main tool that can be used to estimate the
abundance of each oxidation state in specific environments.
According to source categories, the primary source emissions of hexavalent
chromium are the following:
• production of chromium chemicals
• cooling towers
• chrome plating
Based on estimated total chromium emissions and percent hexavalent chromium,
chemical production accounts for approximately four-fifths of total Cr(VI)
emissions. Theoretically, much of these emissions are transformed into
Cr(ZII) over a protracted period of time.
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The most recent data available from EPA's National Air Data Bank, (NADB),
for total chromium shows that the highest 24-hour chromium level nationwide
was 0.6 ug/m3, in Camden, New Jersey. With the use of standard
meteorological dispersion factors (U.S. EPA, 1977), the 24-hour reading
t
translates into a 1-hour level of 1.5 ug/m3. The maximum annual mean
(arithmetic) also in Camden, for 1984 was 0.08. But on average, annual levels
nationwide rarely exceed the limit of detection: 0.005 ug/m3.
Effects on the Respiratory System from Chromium Exposure
From a review of the research published since the completion of the 1984
HAD on Chromium, together with earlier material, the lowest observable effect
levels are from subchronic exposures to concentrations at about 1 ug/m3
Cr(VI) (see the Summary Table). Most of these studies have reported on nasal
and cutaneous pathology associated with a protracted exposure to Cr(VI) in the
workplace. In some cases, however, poor ventilation and direct contact with
chromium dust has been suggested as a causative factor. Only one quantitative
study was available on changes in pulmonary function measurements. The work
by Lindberg and Hedenstierna (1983) indicated that 8-hour exposure to Cr(VI)
could cause transient decreases in lung function measurements.
In describing the fibrogenic potential of welding fumes. Stern et al.,
(1983) noted that the effects from inhaling welding fumes are reversible.
Known as welders lung (welders siderosis) metal-rich particles are deposited
in the lower respiratory tract and regress with time due to various clearance
mechanisms after exposure ceases. For a fraction of welders, the fume
deposition is reversible with the formation of fibrous tissue. Stern et al.,
(1983) investigated the fibrogenic potential of welding fumes through 3600
indexed pathology cases. Twenty-nine cases were indexed as "Arc Welders
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SUMMARY OF THE LOWEST OBSERVED EFFECT LEVELS IN HUMANS
FROM EXPOSURES TO AIRBORNE CHROMIUM COMPOUNDS
I
<
Concentration Occupation
of Chromium
Cr = Catalyst
17 - iis/m1 Plant worker
at 2 plants
Cr(VI) = o.a - 4 2
n/m1
Cr. = Farm machinery
LIT 004 - 0.429 painters/
mg/m1 coaters
Cr(VI) - 0.001 - 0.742
mg/m1
Cr = NO 0.2mg/mJ 97 Silicon
steel rollers
Cr(VI)-0 8-l.Bug/m)
Cr
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SUMMARY OF THE LOWEST OBSER\
FROM EXPOSURES TO AIRBORv.
FECT LEVELS IN HUMANS
.IROMIUM COMPOUNDS
Concentration Occupation Duration of
of Chromium Exposure
MMA/ss O.Zmg/m1 welders
MIG/ss O.lmg/m1
(average)
(Mater soluble CRC)
0.005-0.008 Spray-painters Employed
mg/m3 1-26 years
(TLV=0.05 ing/m1
Author's findings/
Statistical
Significance
Cr(vi) exhibits flbrogenic
potential
Nlstologlcal changes In
the exposed group are
slgnlflcantlly higher than
that of the non-Industrial
control group (p<0.01).
Reference
Stern et al
1983
Nellqulst et al
1983
Although exposure values
were well below TLV.
hlstopathologlcal changes
and clinical symptoms had
developed.
total Cr
0 02 mq/in1
Cr(VI).
0 0006 mg/m3
mean total chrome
0.0071 mg/m1
•
0.2 - 20+ug/m1
Welders I6.a average
years, working
as welder
Electroplaters
104 workers Exposure tine
exposed to correlated with
chrome plating age of the subject
(r:0.6S)
Significant excess
prevalence of cardio-
vascular disease and
a significant Increased
prevalence of some res-
piratory symtoms (productive
cough) among workers.
Association between length
of employment and develop-
ment of Increasingly severe
nasal pathology is
significantly positive
(P = .01)
Nasal septal ulceratton
and perforation seen In
2/3 of subjects exposed
to 20 of uO/m' or
more for a. short term.
Johnson and
Mill us
1980
Cohen and
Kramkowskl
1974
Llndberg and
Nedenstterna
198)
An 8 hour mean exposure
above 2ug/m1 may
cause a transient decrease
In lung function.
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Pneumoconiosis" and revealed welding fumes from the tissue analysis. Exposure
to manual metal arc (MMA) welding fumes indicated an increased fibrogenic
potential in a small number of cases, but was not considered a common factor
for the remaining cases. NO2 was proposed as the common etiological factor.
t
The pneumoconiotic effects of metal inert gas welding (MIG) stainless
steel fumes and MMA mild steel fumes in the lungs of the rat were investigated
by Hicks et al., (1984). Using extremely high concentrations (greater than
1000 mg/m3 for MMA mild steel and 400 mg/m3 for MIG stainless steel), the
investigators found that while both types of particles caused alveolar
epithelial thickening, proliferation of granular pneumocytes, and the
appearance of foam cells in alveoli, soluble chromium constituents displayed
no fibrogenic potential, and acted more as cytotoxic, non-fibrogenic dusts.
Numerous studies have also been reported on sensitization to chromium in
which either inhalation or i.v. injection to chromium triggered sever
bronchoconstriction. Tests conducted on non-occupationally exposed groups
indicate that 1-2% of the population is allergic to chromium. For people with
hand excema, 12-14% of the men and 3% of the women were chromate sensitive.
Asthma induced by chromium salts has also been reported for chromium workers
who exposures exceed 150 ug/m3 Cr(VI) (Circla, 1983).
In conclusion, subtle effects on pulmonary function have been observed in
chromium workers exposed subchronically to greater than 1 ug/m3 Cr(VI).
Similar changes have also been reported by others (e.g. Kilburn, 1986) but at
chromium exposure that were poorly characterized. More information on the
actual exposure to all elements in the setting of these studies would help
determine the influence of other air contaminants on the findings and
dose-response relationship.
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TABLE OF CONTENTS
SECTION PAGE
OVERVIEW AND INTERPRETIVE SUMMARY AND CONCLUSIONS . . ii
1.0 INTRODUCTION 1
r
2.0 BACKGROUND INFORMATION 3
2.1 Chemical and Physical Properties 3
2.2 Production, Use and Release to the Environment . . 5
2.2.1 Production of Chromium Compounds 10
2.2.2 Uses of Chromium and Its Compounds 10
2.2.3 Releases Into the Environment 13
2.3 Environmental Fate, Transport and Concentrations . 13
2.3.1 Air 13
2.3.2 Soil and Water 16
3.0 ANALYTICAL METHODOLOGY . 22
4.0 COMPOUND DISPOSITION AND PHARMACOKINETICS 28
4.1 Uptake and Distribution 28
4.2 Metabolism 29
4.3 Excretion 33
5.0 TOXICOLOGY 35
BIBLIOGRAPHY
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LIST OF TABLES
TABLE
2-1 Physical Properties of Chromium
2-2 Oxidation States of Selected Chromium Compounds and Their
Major Physical Properties ....... f
2-3 Composition of Typical Ferrochromium Alloys and Chromium
Metal 9
2-4 Major Chromium Uses and Key Chromium Chemicals Involved ... 11
2-5 List of Commercially Produced Secondary Chromium Chemicals
and Their General Uses 12
2-6 Source and Estimates of United State Atmospheric Chromium
Emissions 14
2-7 Size Fractions of Chromium Compounds Emitted From a Chromium
Chemical Plant 15
2-8 Number of NADB Observations Exceeding 0.1 ug/m3 Total
Chromium According to Year 17
2-9 NADB Sites Exceeding 0.3 ug/m3 Total Chromium from 1977
to 1983 18
2-10 Highest Measured Total Chromium Concentrations for the Year
1984 19
5-1 Regression Equations for Lung Function Variables in the
Exposed and Reference Group 44
5-2 Summary of Studies on Human Exposures to Chromium Compounds . 48
5-3 Animal Studies on Chromium Disposition, Pharmacokinetics,
and Effects 62
5-4 Vitro Studies on Various Chromium Compounds 75
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1.0 INTRODUCTION
In August 1984, the US EPA's Environmental Criteria and Assessment Office
completed an in-depth review of the scientific literature on chromium and its
compounds. Published as the Health Assessment Document (HAD) for chromium, it
was to serve as the scientific data base for regulatory decision-making of the
Agency, and as such, was to represent an interpretive summary of all relevant
scientific studies. The HAD considered all sources of chromium in the
environment, the likelihood for its exposure to humans, and the possible
consequences to man and lower organisms from its absorption. That information
was integrated into a format that could serve as the basis for qualitative
risk assessments; at the same time, it identified gaps in scientific knowledge
that limited accurate health assessment.
Not withstanding the in-depth analysis, peer-review processes, and
multiple revisions of the 1984 Chromium HAD, several salient scientific
questions still remained unanswered. To address those issues, a new
literature review was initiated, key studies were reanalyzed, and the
conclusions of the original HAD were reassessed. Approximately 175 additional
references on were reviewed for inclusion in the revised HAD. While this
additional material and reanalysis of previously reviewed data add
significantly to understanding the role of chromium on human health, many of
the questions are still not answered completely, but the confidence of the
evaluation has increased markedly. In the addendum the following technical
issues have been addressed:
• Types and persistence of chromium compounds in the environment.
• Adequacy of the sampling and analytical methods as a means to
evaluate the types and amounts in environmental and controlled
study exposures.
• Transformation rates of chromium compounds in the environment.
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• Exposure parameters associated with the key studies.
• In-depth review of pulmonary effects.
• Dose-response relationships of acute, subchronic, and chronic
effects, including chemical and physical properties of the active
chromium species that influence deposition, absorption, and other
pharmacokinetics.
In this revision, all key references reported in the 1984 document were
reviewed again and compared with their description in the HAD. Sometimes no
changes were made; sometimes the original descriptions were redone. The
purpose of this draft is to serve solely as an addendum to the 1984 HAD on
chromium.
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2.0 BACKGROUND INFORMATION
2.1 Chemical and Physical Properties
Chromium is one of the most important metals used in industry today.
Discovered in 1797 by the French chemist Louis Vanguelin, chromium was a key
t
ingredient in the industrial revolution. Table 2-1 lists its properties.
Although chromium exists in several oxidation states, from -2 to +6, only
chromium +3 and +6 (Cr(III) and Cr(VI)) have been studied moderately in
organic chemistry research. The action of these two forms on biological
systems are poorly characterized. The intermediate oxidation state of
chromium +4 and +5 may also have an important role in acting with biological
systems, but until recently virtually no biological research was conducted on
these species.
Cr(III) state is the most stable form of chromium. In neutral and basic
solutions, Cr(III) forms binuclear and polynuclear compounds in which adjacent
chromium atoms are linked through hydroxy-(OH) or oxo-(O) bridges.
Interestingly, Cr(III) forms stable complexes with amino acids and peptides.
Cr(III) also has a strong tendency to form hexacoordinated octahedral
complexes with ligands, such as water, ammonia, urea, ethylenediamine,
halides, sulfates, and organic acids. These relatively stable complex
formations (Cotton and Wilkinson, 1972; Kiilunen et al., 1983) can prevent
precipitation of Cr(III) at pH values at which it would otherwise precipitate,
and it is unlikely that at normal pH values further oxidation of Cr(III)
occurs (Hartford, 1986).
Cr(VI) exists in solution as hydrochromate, chromate, and dichromate ionic
species. The proportion of each ion in solution is dependent on pH. In
strongly basic and neutral pHs, the chromate form predominates. As the pH is
lowered, the hydrochromate concentration increases. At very low pHs, the
dichromate species predominates. In the pH ranges encountered in natural
water, the predominant forms are hydrochromate ions (63.6%) at pH 6.0 to 6.2
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TABLE 2-1
PHYSICAL PROPERTIES OF CHROMIUM
Property
Value
atomic weight
isotopes, %
50
52
53
54
crystal structure
density at 20°C, g/cm3
melting point, °C
boiling point, °C
vapor pressure 130 Pab,°Ca
heat of fusion, kJ/mol
latent heat of vaporization at bp0 kJ/molb
specific heat at 25°C, JcJ/(mol-K)°
linear coefficient of thermal expansion at 20°C
thermal conductivity at 20°C, W/
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and chromate ion (95.7%) at pH 7.8 to 8.5. The oxidizing ability of Cr(VI) in
aqueous solution is pH dependent. The oxidation potential of Cr(VZ) increases
at lower pHs. The ability of Cr(VI) to oxidize organic materials and the
tendency of the resulting Cr(III) to form stable complexes with available
biological ligands afford a reasonable mechanism by which chromium can
interact with the normal biochemistry of man.
The physical properties of various chromium oxidation states and of
several environmentally significant trivalent and hexavalent chromium
compounds are shown in Table 2-2. It should be mentioned that because there
is considerable disagreement in the literature concerning the physical
parameters given in this Table, these values should be accepted with
reservation. The disagreement in the values is possibly due to the reactions
of these compounds with other substances, namely the moisture and air at high
temperatures, impurities, and structural and compositional changes occurring
during the experimental determinations. The composition of typical
ferrochromium alloys and chromium metals is given in Table 2-3. General
information on the chemistry of chromium can be found in the 1984 document.
2.2 Production, Use and Release to the Environment
Considerable information is available on production, use, and release of
chromium into the environment. Much less information is available on the
forms of chromium in the environment. While it is assumed that Cr(III) and
Cr(IV) comprise most of the the total environmental chromium, the biological
importance of the other oxidation states cannot be ruled out completely.
This section is limited to new information not presented in the 1984 HAD.
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Oxidation State
Compound
TABLE 2-2 OXIDATION STATES OF SELECTED CHROMIUM COMPOUNDS AND THEIR
MAJOR PHYSICAL PROPERTIES
Formula
Density
(q/cm3)
Helling Point
Boiling Point
I ing
T°CJ
Solubility
Oxidation State 0
Chromium carbonyl
Cr(CO)6
1 77
150 (decomposes)
(scaled tube)
1SI (decomposes)
Slightly soluble in CC1«,
insoluble in H20,
(C7HS)20. C2HjOM.
C6N6
Dibenzene-
Chromium) 0)
Oxidation State * 1
Blg(biphenyl)-
Chroumium (I)
iodide
Oxidation State » 2
Chromous acetate
i Chromous chloride
en
1 Chromous amonium
sulfate
Oxidation State + 3
Chromic acetate
Chromic chloride
Chromic chloride.
hexahydrate
(CcH6)2Cr
(Cr?(C2HJOj)2S04*6H20
Cr(CHjCOO)j«H20
CrCl,
(Cr(H20)4Clr)Cl • 2H70
(Cr(H20)s)Cl3
1 519
1 .617
1 79
2 93
NR
2 76
1 76
NR
2H1-285
I 78
HIS
NR
I ISO
H3
NR
Sublimes ISO
(vacuum)
Deccomposes
II20
NR
1300
(sublimes)
NR
NR
Insoluble in H20;
soluble in
Soluble in
C2HSOH.
Slightly soluble in
H20: soluble in acide
Soluble in H20 to blue
solution, absorbs 0*
Soluble in H20.
absorbs 02
Slightly soluble
insoluble
SB S at 2S°C
soluble
Chromic formate.
hexahydrate
(Cr(HCOO)j).6N?0
NR
decomposes
.ibovc 300
NR
soluble
Chromic oxide
S 21
2266
4000
insoluble
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TABLE 2-2 OXIDATION STATES OF SELECTED CHROMIUM COMPOUNDS AND THEIR
MAJOR PHYSICAL PROPERTIES
(CONTINUED)
Oxidation State
Compound
Formula
Density
(g/cni1)
Mcltinq Point
~ " " "
Boiling Point
Solubility
Oxidation State + 3 (Continued)
Chromic phosphate CrPOq* 2H20
hydrated CrPOo* 6H20
2 f.2 (32 i°C)
2 121 (14°C)
MR
100
NR
NR
slightly soluble
insoluble
Chromic sulfate
3 012
NR
NR
insoluble
Chromic sulfate,
Hydrated
15H:0
18H?0
1.867 (17°C)
1 7 (22°C)
100
100 (-12H 0)
100(-100 H..O)
NR
soluble
120 at 20°C
I
-J
I
Oxidation state +4
Chromium(IV) oxide CrO-
Dirk -brown or
bl.ick powder
1 98
(calculated)
Chromium (IV
chloride
Crd
Oxidation state *5
Barium chromate (V) Baj(Cr0.i).-
Bl.ick-green
crystals
Oxidation state +6
Ammonium chromate
Ammonium dichromate
Barium chromate
Chromium (VI) oxide
Lead chromate
MH.,)2Cr20;
BaCrOa
Cr03
PbCrO«
2 155-r,
«. 498rr.
2.7025
6 121S
Decomposes
lo Cr?0i
H30
Soluble in acids to
Cr1* and Cr6*
clucomposc'
1HO
tlocomposes
decompose'.
Slightly decomposes
in HjO; soluble in
dilute acids to
Crj+ and Crs+
NR
NR
NR
decomposes
decomposes
40.5 at 30°C
30.8 at 15°C
3.4 x 10-4
at 160°C
67.45 at 100°C
5.8 x 10.6 at
25°C
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TABLE 22 OXIDATION STATES Of SELECTED CHROMIUM COMPOUNDS AND THEIR
MAJOR PHiSICAL PROPERTIES
(CONTINUED)
Oxidation State Formula
Compound
Oxidation state «6 (Continued)
Mercurous (I) Chromate Hq -CrOq
Mercuric (II) Chromate HgCr04
Potassium Chromate KrCrO«
Potassium dichromale * Cr207
Sodium Chromate NvCrO*
Sodium di Chromate N.I .Cr207 • 2h?0
dihydrate
t
00
Density McUmfl_Pfiuil
(q/CHl1) T"C)
NR
NR decompose'.
2 732,8 Cl?l
2 676 .. 3r'M
2 723 .. 7Q:
2 318-., HI 6
( incongi lu-nt )
Boiling Point
NR
NR i
NR
SOO
decomposes
NR
100
decomposes
Solubility
very slightly soluble
slightly soluble, decomposes
62.9 at 20°C
4.9 at 0°C
102 at 100°C
87 3 at 30°C
180 at 20°C
Sources US EPA 1984 a.b
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TABLE 2-3
COMPOSITION OF TYPICAL FERROCHROMIUM ALLOYS AND CHROMIUM METAL
VO
I
Grade
ferrochromium
high-carbon
high-carbon, high-silicon
blocking chrome
exothermic ferrochrome
foundry ferrochrome
refined chrome
SM ferrochrome
charge chromium
50-55 percent chromium
66-70 percent chromium
low-carbon:
0.025 percent carbon
0.05 percent carbon
Simplex
ferrochromium-silicon:
36/40 grade
40/43 grade
chromium metal
electrolytic
aluminothermic
Chromium
66-70
55-63
41-51
55-63
53-63
60-65
50-56
66-70
67-75
67-75
63-71
35-37
39-41
99. 3C
99. 3C
Silicon
1-2
8-12
9-14
8-12
2.5a
4-6
3-6
3
lb
lb
2.0a
39-41
42-45
0.01a
0.15a
Carbon
5-6.5
4-6
3.6-6.4
4-6
3-5
4-6
6-8
6-6.5
0.025a
0.05a
0.01 or 0.025
0.05a
0.05a
0.02a
0.05a
Sulfur3 Phosphorus8 Other"
0.04 0.03
0.03
0.03
0.03
4-6 manganese
0.04 0.03
0.04 0.03
0.025 0.03
0.025 0.03
-
0.03 0.5 oxygen*
0.05 nitrogen8
0.015 0.01 0.2 oxygen8
0.3 aluminum8
"Maximum value.
"Difference between sum of percentages shown and 100 percent is chiefly iron content.
cMinimum value.
Source: U.S. EPA 1984b
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2.2.1 Production of Chromium Compounds
According to the U.S EPA's 1984 report on chromium emission factors,
chromite ore has not been mined commercially in the United States since 1961,
when the I). S. Defense Production Act was phased out, eliminating government
i
subsidization of chromite mining activities. The United States owns chromite
deposits in Maryland, Montana, North Carolina, California, Wyoming,
Washington, Oregon, Texas, and Pennsylvania; however, the low chromium content
of these deposits precludes economical mining. In 1982, the U.S. imported 456
Gg (507,000 tons) of chromite, mostly from Albania (0.8 percent), Finland (8.9
percent), Madagascar (8.1 percent), Pakistan (0.6 percent), the Phillipines
(13.8 percent). South Africa (54.6 percent), Turkey (6.3 percent), and the
U.S.S.R. (6.7 percent).
In 1984 sodium chromate and sodium dichromate U.S. annual production
capacity was 204,000 metric tons. Chromic acid annual production capacity
totaled 38,000 metric tons (Blanchard, 1986). The industrial processes for
the production of chromium metal and compounds were described adequately in
the previous document.
2.2.2 Uses of Chromium and Its Compounds
The 1984 Chromium HAD noted that metallurgical and chemical usages
constituted 82% of the total United States chromium consumption in 1979. The
ma3or chromium chemicals, uses, and the number of production sites are
presented in Table 2-4 and 2-5. As noted in the 1984 Chromium HAD, the
pattern of chromium consumption in the United States has been consistent over
the last 20 years. However the use of chromite and chrome alloys in the
refractory industry is beginning to decline as open hearth furnaces are
replaced by basic-oxygen furnaces. In the future, growth in chromium usage is
expected in the metallurgical and chemical sectors.
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TABLE 2-4
MAJOR CHROMIUM USES AND KEY CHROMIUM CHEMICALS INVOLVED
Chromium Chemical
Use Area
Key Chromium
Chenvicals Involved
Paints and Pigments
Leather Tanning Liquor
Metal Finishing and Plating
Corrosion Inhibitors
Catalysts
Drilling Muds
Wood Preservatives
Textile Mordants and Dyes
Chrome Yellow"
Chrome Orange3
Chrome Oxide Green
Molybdate Orange3
Chrome Green
Basic Chromium Sulfate
Chromic Acid
Zinc Chromate
Zinc Tetroxychromate
Strontium Chromate
Lithium Chromate
Cadmium Chromate
Copper Chromate
Magnesium Dichromate
Nickel Chromate
Copper Chromite
Chromium Lignosulfonate
Chrome Copper Arsenate
Chrome Zinc Chloride
Chromic Chromate
Chromic Chloride (hydrated)
Chromic Fluoride
Chromic Lactate
3Contains lead chromate.
Source: U.S. EPA 1984b
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TABLE 2-5
LIST OF COMMERCIALLY PRODUCED SECONDARY CHROMIUM CHEMICALS AND THEIR GENERAL USES
Chromium ChemicalA
Number of Production Sites8
General Use
to
i
Chromic acid (Chromium trloxide)
Chromium acetate
Chromium acetylacetonate
Chromium monoborlde
Chromium carbide
Chromium carbonyl
Chromium chloride, basic
Chromium chloride
Chromium dlborlde
Chromium di fluoride
Chromium dioxide
Chromium 2-ethylexanoate (Chromic octoate)
Chromium fluoride
Chromium hydroxide
Chromium hydroxy di acetate
Chromium hydroxy dichloride
Chromium naphthenate
Chromium nitrate
Chromium oleate
Chromium oxide (Chrome oxide green)
Chromium phosphate
Chromium potassium sulfate (Chrome alum)
Chromium sulfate
Chromium sulfate, basic
Chromium triacetate
Chromium trifluoride
Chrome lignosulfate
Potassium chromate
Potassium dichromate
Lead chromate
Zinc chromate
Ammonium dichromate
Barium chromate
Calcium chromate
Cesium chromate
Copper chromate, basic
Magnesium chromate
Straontium chromate
Iron chromite
2
6
3
1
l
2
1
2
1
1
1
2
1
1
1
1
2
2
2
6
2
1
2
5
3
2
2
3
1
1
1
3
2
Electroplating
Printing and dyeing textiles
Catalysts, antiknock compounds
Unknown
Metallurgy
Catalysts
Metal treatment
Metal treatment
Unknown
Catalysts
Magnetic Tape
Unknown
Mordants, catalysts
Pigments, catalysts
Unknown
Unknown
Textile preservative
Catalysts, corrosion control
Unknown
Pigments
Pigments, catalysts
Photographic emulsions
Catalysts, dyeing, tanning
Tanning
Unknown
Printing, dyeing, catalysts
Drilling muds
Metal treatment
Tanning, dyeing, pigments
Pigments
Corrosion control
Printing, pyrotechnics
Pyrotechnics
Corrosion control
Electronics
Wood preservative
Refractory, catalysts
Corrosion control pigment
Refractory
AList does not Include sodium chromate and sodium dichromate, which are primary chemicals.
"Several sites product multiple chromium chemicals.
Source: U.S. EPA 1984b
-------
2.2.3 Releases Into the Environment
Little new information was found on the emission rates of chromium into
the environment. Table 2-6 lists sources, emission rates, and estimated
percent hexavalent chromium in the U.S. As a source category, the production
i
of chromium chemicals account for approximately 15% of the total chromium
emissions. However, when compared with estimated percent of hexavalent
chromium emissions, chromium chemical production accounts for 80% of total
Cr(VI).
2.3 Environmental Fate, Transport and Concentrations
2.3.1 Air
Chromium occurs in the environment primarily in two oxidation states:
Cr(III) and Cr(VI). The forms, and uses were shown in the previous tables.
Reactions of chromium in the environment under typical atmospheric conditions,
as theorized by Seigneur (1986) and others, revealed that Cr(VI) may be
reduced to Cr(III) at a significant rate by vanadium (V2+, V3«., and
V02+), Fe2 + , HSOi and As(III). Conversely, the oxidation of Cr(III)
to Cr(VI) may only occur in the atmosphere at a significant rate if (1)
Cr(III) is emitted as a chromium salt and not Cr203 and (2) at least 1
percent of Mn in atmospheric aerosols in present as MnOz. The time required
for these reactions to occur in the environment, given all the other species
present, is unknown. In studies conducted by Butler et al., (1986) and
others, chromium was found to occur in the smaller particle size fractions.
Table 2-7 "contains the results of combining six impactor runs from the two
kilns at a chemical plant. The size fractions represented were for particle
sizes greater than 10 urn, 2-10 urn, and less than 2 urn in mean
aerodynamic diameter. Note that although only 38 percent of the total mass
was collected in the size range 10 urn and below, 85 percent of the total
-13-
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TABLE 2-6
SOURCE AND ESTIMATES OF UNITED STATES ATMOSPHERIC CHROMIUM EMISSIONS*
Source Category
Chrome Ore
Refining
Ferrochromium
Production
Chromium Chemicals
Production (Primary
and Secondary
Refractory Pro-
duction
Sewage Sludge
Incineration
Municipal Refuse
Incineration
Speciality/Steel
Production
Utility Cooling
Towers
Refining Cooling
Towers
Cement Production
Chrome Plating
Combustion of Coal
and Oil
Boilers
Process heaters
Estimated Chromium Emissions Estimated Hexava-
Number of (Metric Tons/Jfr) lent Chromium
Sources %
6 3 <1
1 03 4.4
37 450-900 99.4
10 90 <6
141 25-30 <1
129
18 2870 <4
Many 5 -100
Many - ~100
145 16
Many - -100
Many
737 <1
556 <1
4825-5275
'Sources: Blanchard, 1986; Radian Corporation, 1984. US EPA, 1984b.
-14-
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TABLE 2-7
CHEMICAL PLANT PARTICLE SIZE RESULTS
Size Fraction Particulate
nun mg 4, of
>10 39.9
2-10 6.6
<2 18.4
Total 64.9
Mass
Total
62
10
28
Cr(VI)
mg
84.2
197.8
286.1
568.1
Extracted
% of Total
15
35
50
Cr(III)
mg "'
349
511
621
1481
Extracted
I of Total
23
35
42
Source: Butler et al., (1986).
-15-
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Cr(VI) was contained in that range. In fact, 50 percent of the Cr(VI) was
found in the size fraction below 2 \m, although this fraction was only 28
percent of the total mass collected in the impactors. These data are very
similar to results in the initial ferrochrome particulate analysis reported
t
earlier. In that report (Cox et al., 1985), it was determined by scanning
electron microscopy that the small (largely submicron) particles and
aggregates of the particles contained the bulk of the Cr(VI)."
In general, 24 hour ambient air chromium levels rarely exceed 0.1
ug/m3. From EPA's NADB inventory of daily chromium monitoring, only eight
observations at 173 sites exceeded 0.1 ug/m3 as a 24-hour avarage in
1984. Table 2-8 lists the number of observations exceeding 0.1 ug/m3 from
1977 through 1984. In fact, only about 50 24-hour observations out of
approximately one-half million, have exceeded 0.3 ug/m3 chromium from 1977
to 1984. Table 2-9 shows the 26 sites at which those 50 observations
occurred. Table 2-10 lists the most recent information available from EPA's
National Aerometric Data Bank. Twenty-four hour values for total chromium,
measured by neutron activation analysis, are presented for the thirteen
highest sites, from an examination of 173 site records for the year 1984.
From these sites, which comprise the nationwide network, the highest observed
24-hour total chromium concentration was 0.6 ug/m3 (in Camden, N.J.).
Additionally, only seven of the 173 sites exceeded 0.1 ug/m3. It should
be noted that these monitors are generally not located near sources that emit
significant quantities of chromium (Blancherd, 1986).
2.3.2 Soil and Water
Bartlett (1986) investigated the chemistry of chromium in soils and also
noted the importance of the presence of manganese oxide. He found that the
-16-
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TABLE 2-8
NUMBER OF NADB OBSERVATIONS EXCEEDING 0.1 pg/m3
TOTAL CHROMIUM ACCORDING TO YEAR*
1977 1978 1979 1980 1981 . 1982 1983 1984
Number 28 21 19 17 18 17 29
*NADB Chromium Inventory from 1977-1984; total of 2106 yearly maxima.
-17-
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TABLE 2-9
NADB SITES EXCEEDING 0.3 ug/m3 TOTAL CHROMIUM FROM 1977 TO 1983
Site
Stubenville, OH
East Chicago, IL
Pasadena, CA
Clarion Co. , PA
Greenville, SC
Columbia, SC
Huntington, WV
Torrance, CA
Niagara Falls, NY
Baltimore, MD
Cincinnati, OH
Abilene, TX
Camden, NJ
New Orleans, LA
Corpus Christe, TX
(2 locations)
Brownsville, TX
Wichita, KS
Kansas City, KS
Shawnee, KS
Year
1977
1979
1977
1977
1977
1977
1977
1977
1977
1979
1979
1980
1982
1983
1979
1980
1980
1981
1981
1981
1981
1981
1982
1983
1983
1983
No. of
Samples
21
28
24
32
25
27
11
6
29
30
26
6
19
23
28
53
19
30
30
33
36
51
58
56
42
57
Max
Obs
2.0550
0.6839
1.0750
0.5600
0.4052
0.4031
0.3045
0.3742
0.3153
0.5590
0.4589
0.5794
0.4310
0.4466
0.4316
0.9100
0.4037
0.3461
1.0710
0.7300
0.3500
0.3900
0.3500
0.4000
0.4400
0.3900
Arith
Mean
ug/m3
0.5251*
0.1212*
0.1170
0.0400*
0.1475*
0.0311
0.0360*
0.0885*
0.0306
0.0389
0.0935
0.2264
0.1019
0.0854
0.0451
0.0400
0.0903
0.0603
0.0436
0.1200
0.0700
0.0300
0.0150
0.0420
0.0320
0.0260
*Value derived from data that did not meet SAROAD criteria.
Source: Derived from Data Files From 1977-1984.
-18-
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TABLE 2-10
HIGHEST MEASURED TOTAL CHROMIUM CONCENTRATIONS FOR THE YEAR 1984
Camden, N.J.
Reading, PA
Dundalk, M.D.
Baltimore, M.D.
(1st site: Fire Dept.)
Youngstown, OH
St. Louis Park, MN
Columbus, GA
Cleveland, OH
(2nd site: Broadway Ave.)
Erie, PA
Philadelphia, PA
Max
Obs
0.6017
0.3530
0.3442
0.3197
0.1649
0.1594
0.1502
0.1183
0.0993
0.0839
2nd
Max
0.2190
0.1466
0.1386
0.2271
0.0163
0.0318
, Arit.
Mean
ug/m3
0.0834
0.0618
0.0497
0.0626
0.0181
0.0114
0.0052* 0.0184
0.1053
0.0466
0.0428
0.0332
0.0161
0.0188
Geom.
Mean
<±>
0.0249
0.0369
0.0278
0.0236
0.0085
0.0064
0.0071
0.0221
0.0096
0.0108
Geom.
Std
Dev
.79903
.78416
.65148
.25783
.54443
.02481
.75682
.57376
.54879
.78828
(2nd site: Edgemont & Auburn St.)
Milwaukee, WI
(1st site: Greenfield Ave.)
Huntington, WV
Chattanooga, TN
(2nd site: E llth St.)
0.0767 0.0416 0.0149 0.0103 .26647
0.0717 0.0220 0.0128 0.0075 .37221
0.0713 0.0200 0.0134 0.0082 .37701
*Apparent error in the data analysis.
Source: Calculated from the 1984 files of EPA's National Aerometric Data Bank.
-19-
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key parameter for oxidizing Cr(III) to Cr(VI) was manganese oxide, which
becomes reduced as the Cr(III) is oxidized. According to Bartlett, this
phenomenon has not been reported previously because dried, stored lab-dirt
samples had been studied. In such samples, reducing organics are released and
i
manganese oxides are temporarily reduced or occluded. As such, Bartlett noted
that the Federal toxicity test using acetic acid eliminates the possibility of
finding Cr(VI) in most soils.
Whether or not Cr(III) present in soil, or added to it, is oxidized
depends upon the interaction between the chemical forms of the chromium and of
the manganese oxides. If the Cr(III) is "moderately available", the
regulating factor appears to be the "freshness" of the manganese oxide
surfaces, and this is related to quantities of oxidizable organic substances
along with soil temperature, moisture, aeration, and drying. Strongly bound
Cr(III) may remain reduced in soils, although small amounts are oxidized a
narrowly-defined optimum. Organic forms are more easily oxidized than
insoluble oxides. Reduction of Cr(VI) added to soils occurs readily if pH is
low and an organic energy source is available. Because soils are not
equilibrium systems, reduction of CR(VI) and oxidation of Cr(III) may occur at
the same time in the same sample of soil.
To predict maximum elemental concentrations of chromium in groundwaters,
Rai (1986), investigated the thermochemical data for chromium bearing solids
that form in geologic environments and the mechanistic data for reactions that
control the distribution of chormium redox species. The solubilities of
freshly precipitated Cr(OH)3 and CrxFei-x(OH)3 were investigated to
provide thermochemical data, previously unavailable or unreliable, for
equilibrium constants of solubility reactions and for Cr(III) hydrolysis
constants. He also investigated the effects of Mn oxides and
Fe(II)-containing minerals on Cr(III)/Cr(VI) redox transformations.
-20-
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His investigation indicated that the oxidation of aqueous Cr(III) by
MnOz was significantly more rapid than oxidation by dissolved oxygen, which
is the only other oxidant likely to transform Cr(III) to Cr(VI). Additional
kinetic studies have shown that aqueous Cr(VI) is reduced to Cr(III) by trace
i
amounts of ferrous iron in soil minerals. Concentrations of aqueous Cr(III)
that are produced by reduction are consistent with the solubility of
CrxFei-x(OH)3. Rai concluded that redox reactions mediated by solid
surfaces, which are often ignored, are important in determining the redox
status of elements in sediments.
-21-
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3.0 ANALYTICAL METHODOLOGY
The previous review of analytical methods for the collection and analysis
of chromium is supplemented here by additional work evaluating commonly used
and new procedures. Carelli (1981) investigated the source of errors of
chromium measurements using S-diphenylcarbazide in a chromium and zinc plating
plant. He found that the absorbence of the complex Cr(VI)-S-diphenylcarbazide
was a function of time if Cr(VI) was extracted from the atmospheric
particulate according to Thornsen and Stern's (1979) method. Also, the
absorbence depression was found to depend on the Cr(VI) extraction method used
and could be essentially complete if Abe11 and Carlberg's (1974) extractive
method was used on these types of samples. Absorbence decrease is stronger if
large amounts of Fe(III) are present. Absorbence measurements should be made
within 1 minute in the presence of 500 ug of Fe(III) with 0.4 ug of Cr(VI).
Only slight interferences were found to occur at higher concentrations of
chromate, i.e. 4.0 ug of Cr(VI). The absorbence of alkaline extracts reached
a maximum after 2 min and was constant for about 3 min then decreased after 5
mm. Cr(VI) acid extraction gives rise to an erroneous determination of the
Cr(VI) content of these environmental samples due to an enhancement of the
matrix effect which leads to a significant reduction in the measured Cr(VI)
content. Cr(VI) additions to alkaline-extracted samples showed only a slight
depressive interference, which could be compensated for with the use of the
standard addition method. The Thomsen and Stern method was reliable if the
standard addition method is applied and if absorbence measurements are made
within the time limits suggested.
Blomquist et al., 1983, compared the DPC method (1,5-diphenylcarbo-
hydrazide of Abe11 and Carlberg) with the carbonate method of (Thomsen and
Stern), in manual metal arc welding and chromium plating plants. To prepare
samples for analysis by the DPC method, Abe11 and Carlberg recommended
-22-
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leaching in 0.5 M sulfuric acid. But this procedure results in a significant
reduction of Cr(VI) within 10 min. Studies on the stability of Cr(VI) show
that sodium acetate buffer is more suitable for leaching the filters. As
pointed out by Abe11 and Carlberg, to avoid reduction of the Cr(VI), sampling
i
should be performed on polyvinyl chloride filters, but if the polyvinyl
chloride filters are stored for several days, the Cr(VI) is more difficult to
recover from the filters. The leaching time has to be extended to at least 15
min. The DPC method, based on sampling on polyvinyl chloride filters and
sodium acetate buffer leaching, was demonstrated to give the same results as
the more laborious carbonate method, for manual metal arc welding analysis.
For the sampling and analysis of airborne Cr(VI) in a chromium plating plant,
the DPC method and atomic absorption spectrometer analysis are suitable. The
use of sodium acetate buffer for leaching the samples also solves the problem
of bivalent iron interference.
Naran^it et al.. 1979 utilized atomic absorption spectrometry for
quantification and anion- and cation-exchange resins for separation. At pH
3-5, there is no loss of Cr(III) as the hydroxide nor reduction of Cr(VI) by
Fe(II). It is only under these pH conditions that valid Cr(III)/Cr(VI) data
can be obtained for aqueous extracts of welding fumes. Composition of the
welding rods can cause a difference in the water-soluble chromium content of
the welding fumes. A combination of anion-exchange and cation-exchange
systems is necessary to obtain quantitative results in the determination of
Cr(III) and Cr(VI) in the aqueous extracts. Extent of oxidation of Cr •»
Cr(III) •> Cr(VI) and, as such, the ratio of Cr(III)/Cr(VI) depend on the
method of welding or reduction intensity coefficents of Si and Mn. Also a
very-lean flame (air-acetylene) helps avoid interferences by other anionic and
cationic species in welding flames for atomic absorption but results in a
-23-
-------
5-fold loss of sensitivity. A standard addition method can compensate for
these problems.
Slavin (1981) described the figures of merit for graphite furnace atomic
absorption. The technique requires more skill than flame AAS. Good analysis
t
with the furnace requires that compensation be provided for light that is
scattered by the sample at the same wavelength at which the analyte metal has
its characteristic absorption. Analytical errors have been reported because
chromium is volatized at different temperatures depending upon the compounds
in which it is bound and probably upon large variations in the mass of the
residue still present at the moment of atomization. The different
temperatures produce a different analytical signal. This error could be
decreased significantly be depositing the sample upon a thin pyrolytic
graphite plate (platform) placed within the furnace tube. Also, high halide
levels will reduce the chromium signal. But, it has been shown that large
amounts of halide can be tolerated if the platform is used for the chromium
determination. The quality of the graphite and the pyrolytic coating plays an
important role in the repeatability of the chromium determination, especially
in complex matrices. Pyrolytically coated tubes have been shown to provide
greater sensitivity than ordinary graphite tubes. Errors also result from the
loss of organic chromium complexes in biological materials during the charring
cycle. Charring conditions should be established by experiments on the
sample, not on inorganic standards.
Studies by Butler et al., (1986) and Cox et al., (1985) explored methods
to determine chromium speciation at various chromium facilities: a
ferrochrome smelter, a chemical plant, and a refractory brick plant. In the
initial study by Cox and colleagues, the source of chromium chosen was a
ferrochrome smelter that processes mixtures of chromium-containing ores and
lime (CaC03) in an electric arc furnace. Both Cr(III)and Cr(VI) species are
-24-
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present in the dust captured by pollution control devices, in this case a
baghouse. Since the baghouse dusts are disposed of in landfills, where
leaching mechanisms can extract species into the environment, the dust
provides a useful analytical sample to determine the amount and chemical state
i
of chromium potentially available for biological uptake (operationally
designated as "bioavailable" chromium). The main goal of the study was to use
nondestructive instrumental techniques in concert with conventional wet
chemical analysis to establish the fraction of bioavailable chromium present
as Cr(VI) An additional objective was the evaluation of various wet chemical
techniques to help establish a reliable, routine approach to environmental
source monitoring or differentiate chromium species, ultimately to include
ambient particle samples.
A bimodal chromium source contribution (small particles enriched in
bioavailable Cr(VI) and large chromite-like particles containing primarily
insoluble Cr(III) was found by the results of wet chemical analysis performed
on size-resolved dust particles. Although particles less than 10 urn in
diameter comprise only 28% of the total particle mass, over 75% of the total
Cr(VI) came from particles in this size range. Furthermore, 55% of the Cr(VI)
detected is concentrated in particles less than 0.7 urn in diameter, which
comprise only about 12% of the total particle mass. It is apparent that the
small soluble particles and aggregates resulting from the smelting process
contain the majority of the Cr(VI).
Approximately half of the total chromium was extractable by acid/base
leaching +**•"•"'•" ^hl??, of which about 40% was Cr(VI). In the follow-up
study by Butler and colleagues, samples from a chemical plant and a brick
plant were added and the results were verified through non-destructive
techniques. Both studies measured chromium concentration at the ppm level
-25-
-------
(mg/m3) and noted the occurrence of Cr(VI) in the small particle size
fractions.
Because occupational exposures comprise the primary health studies on
chromium, it is important to characterize the types of chromium species
present in occupational settings. The most important occupations where health
information on chromium exposure is available are from plating and welding.
Two primary techniques are used in welding stainless steel: manual metal arc
(MMA) and metal inert gas (MIG). MMA welding generates three to four times
more fumes per kg of welded stainless steel than MIG welding at the same
power, and the total chromium content of MMA welding fumes ranges from 2.4% to
7%. Forty to ninety percent of the total chromium appears in a hexavalent and
soluble form. The relative amount of chromium in MIG welding fumes may be
much higher, from 4% to 15%, but the chromium is mostly trivalent or metallic
chromium forms. The relative solubility of the chromium is 1000 times higher
than in MIG welding fumes. A problem associated with studies in welders is
that it is difficult attribute the effects observed only to the chromium
exposure because of other pollutants present in the fume.
The mass median diameter ranges from 0.3-0.6 urn for MMA welding fumes.
The concentrations of Cr, Mn, and Ni in MIG welding fumes are much higher than
in MMA welding fumes, and the particles are very crystalline. Crystalline
particles are considered to be biologically more active than amorphous
particles with the same chemical composition. Other studies such as those of
McllWain and Neumeier (1983) have focused on the amount and type of chromium
emitted from different stainless steel electrodes. For the first types of
electrode tested, total chrome amounted to 9 percent (wt) of all chemicals
emitted, from which Cr(VI) accounted for 5.04% (4.7% was soluble; 0.34%
insoluble) and Cr(III) accounted for 4.2% (1.5% acid soluble; 3.1% insoluble).
-26-
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Rao & Sastri (1982) examined the various methods for the determination of
chromium in natural waters. Spectrophotometry, atomic absorption
spectrometry, neutron activation analysis, and luminescence are applied
extensively, yet all of these methods, except the luminescence methods,
i
require pre-concentration to improve the sensitivity. The major drawback of
these methods is that decontamination of chromium is required, particularly
for spectrophotometric methods. The only method which has been tried
thoroughly for direct determination at low concentration of chromium in
natural waters appears to be the chemiluminescence method. This method,
however, suffers from a series of interferences.
-27-
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4.0 COMPOUND DISPOSITION AND PHARMACOKINETICS
4.1 Uptake and Distribution
Chromium is distributed approximately equally among human tissues with the
exception of lung, which may contain 2 to 3 times the concentration of other
i
tissues. Body chromium content increases during fetal development to a
maximum at birth, then declines steadily with age. Adults contain
approximately 5 to 10 mg total body chromium. Cr(III) is poorly absorbed by
the body regardless of the route of administration, while Cr(VI) is more
readily absorbed. The three principal routes of exposure are 'through the
lungs, gastro-intestinal tract and skin. In the absence of industrial
exposure, the primary means of uptake of chromium is absorption from
chromium-containing food and water by the gastro-intestinal tract. It has
been estimated that 1% of the chromium content of the diet is absorbed. In
occupational exposures, the lungs are the primary route of exposure. Based on
deposition studies with Cr(III), pulmonary absorption amounts to approximately
5%. The skin is considered a minor route of exposure for both Cr(III) and
Cr(VI) compounds. Occupationally exposed workers can have chromium
concentrations in lung that are 300-fold higher than non-exposed controls, and
concentrations in liver, kidney and adrenal glands that are 2 to 4-fold,
10-fold, and 10 to 50-fold higher, respectively. Studies by Glaser et al.,
(1985) and Kollmeier et al., (1985) have shown similar distribution and
retention parameters.
To understand the kinetics of different welding fumes, Kalliomaki, et al.,
(1983) investigated the retention and clearance of metal inert gas (MIG)
stainless steel welding fumes in rats and the results were compared with the
corresponding results for manual metal arc (MMA) stainless steel welding fumes
in rats. For MIG welding fumes, the measured retention corresponded well with
the estimated amount of inhaled chromium. The clearance was very slow, with a
-28-
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half-time (Tl/2) of approximately 240 days. The estimated value of Tl/2 was
not very reliable because of the great variations in chromium concentrations
within each group. The retention rate for MMA welding fumes was higher, and
the clearance was slower than expected, (Tl/2=40d), when the high percentage
of soluble chromium in the original MMA stainless steel welding fumes (40-90%)
was taken into consideration. It has been suggested that water soluble
hexavalent chromium compounds may be reduced to trivalent chromium or
transformed into an insoluble Cr(VI) compound in humid surroundings like the
airways.
In experimental studies with animals, Cr(VI) is taken up much more readily
than Cr(III). Following oral administration, approximately 10% of the dose of
Cr(VI) is absorbed, while less than 0.5% of the Cr(III) dose is absorbed.
Cr(VI) can be reduced to Cr(III) by the gastro-intestinal tract, thereby
reducing uptake. Following intratracheal or intravenous exposure, both
Cr(III) and Cr(VI) are distributed throughout the body, with the highest
concentrations in liver, kidneys and lungs, which are the target organs for
toxicity.
In blood, Cr(III) is bound principally to serum proteins, while Cr(VI) is
specifically taken up by red blood cells and bound to hemoglobin. Cellular
uptake of Cr(III) is very poor, while Cr(VI) probably crosses the membrane by
simple diffusion. The intracellular distribution of Cr(III) is different from
that of Cr(VI), probably as a result of metabolism. Approximately 10% of the
cellular Cr(VI) content is associated with the nucleus, while 50% of the total
cellular Cr(III) is nuclear.
4.2 Metabolism
Metabolism of Cr(VI) involves cellular reduction of Cr(VI) by small
molecules and enzyme systems, a process which generates reactive intermediates
-29-
-------
and Cr(III). The metabolites ultimately bind to cellular constituents and may
result in impairment of their normal function in the cell. In vitro, ascorbic
acid (vitamin C) and the thiols, glutathione, cysteine, cysteamine, lipoic
acid, coenzyme A and coenzyme M reduce Cr(VI) at a significant rate under
i
physiological conditions. Depletion of glutathione in rat liver in vivo
results in decreased reduction of Cr(VI) in the liver and increased excretion
of Cr(VI) in the bile. The ability of Cr(VI) to damage DMA in primary
cultures of chick embryo hepatocytes is decreased by depletion of glutathione
and increased by induction of glutathione. Reaction of Cr(VI) with
glutathione in vitro results in the formation of Cr(III) and another
unidentified radical species. DT-diaphorase has been identified as the major
cytosolic enzyme contributing to Cr(VI) reduction.
Components of the electron-transport chains of both mitochondria and the
endoplasmic reticulum are capable of metabolizing Cr(VI). The NADPH-dependent
Cr(VI) reductase activity of rate liver microsomes has been identified as
cytochrome P-450. The microsomal reduction of chromium is exclusively
NADPH-dependent, but the main cellular activity can be detected in cytosolic
fractions and, as such, can be ascribed to enzyme-catalyzed mechanisms, e.g.,
the DT-diaphorase activity. A minor contribution is provided by nonenzymatic
components, notably by some electron donors and chiefly by GSH.
Interestingly, the metabolic Cr(VI) reduction is selectively enhanced not only
by enzyme inducers but, in the rat lung, it is also stimulated by the repeated
intratracheal administration of high doses of Cr(VI) itself; this is
consistent with a local autoinduction of Cr(VI) metabolism. Additional
detoxifying mechanisms occur in the human epithelial-lining fluid, i.e. in the
extracellular environment of the lower respiratory tract, and especially in
pulmonary alveolar macrophages (PAM). The specific activity in these
-30-
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defensive cells is even higher than in liver or lung cells, similar reductive
mechanisms being involved.
Bryson and Goodall (1983) studied the acute and subacute toxicities of
several Cr(III) and Cr(VI) compounds in mice and related the toxicities to the
i
pharmacokinetics. The distal median lethal doses (more than 10 days after
treatment) averaged (17.9 + 1.8) x 10"s g Cr/g body weight regardless of the
oxidation state of the chromium compound injected, (Cr(III) sulfate may be an
exception), but acute toxicity (3 days) was much greater with Cr(VI)
compounds. Acid digests of entire male mice that were administered i.p.
one-sixth of the distal LDSo. either once or repeatedly at weekly intervals,
were analysed to determine the whole body persistence and clearance kinetics
of Cr. Mice dosed once with Cr(III) retained 6.5 times more chromium at 21
days than mice treated with Cr(VI). When Cr(III) was given at weekly
intervals, mice accumulated 6 times more chromium by 8 weeks than
Cr(VI)-treated mice, though only the latter showed symptoms of chronic
toxicity. Whole body chromium concentrations continued to rise with further
Cr(III) treatments, but slowly declined with Cr(VI). Analyses of fecal and
urinary excretion confirmed most of the urinary chromium clearance occurred
soon after injection, and that chromium excretion from Cr(VI)-treated animals
was much faster in both urine and feces than from mice given Cr(III). The
differential storage and clearance kinetics of Cr(III) and Cr(VI) compounds
may be significant in experimental chromium carcinogenesis studies and in the
toxicology of chromium in workers exposed industrially to potentially
carcinogenic Cr-containing dusts or aerosols. Cr(VI) reduction is
significantly enhanced in smokers, which mainly depended on an increase in
total proteins in smokers' PAM. All the described mechanisms are likely to
determine a selection of the possible in vivo targets of Cr. Also in the
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lung, which is the only recognized target of Cr(VI) carcinogenicity in humans,
the documented defense pathways are expected to constitute a metabolically
regulated threshold limiting the potential carcinogenicity of this metal
species. According to Bencko (1985), the absorption values derived from the
»
chromium urinary excretion data may be greatly misleading, by neglecting the
role played by the digestive tract in the chromium elimination from the
organism. For instance, rats given a single parenteral dose of chromium
eliminate in their feces about 4% of Cr(III) and 7% of Cr(VI) within the first
24 hours after administration, and also the biliary excretion of the
hexavalent chromium is significantly higher than that of Cr(III).
Inhalation experiments with dust made up of water-soluble salts of Cr(VI)
have revealed that the Cr(VI) is absorbed from the lungs into the blood stream
(primarily into erythrocytes) prior to its reduction to Cr(III). Under these
experimental conditions, a major part of inhaled chromium is excreted in the
urine. However, in guinea pigs exposed to chromium in the form of fumes
produced by shielding-gas welding, which is known to prevent chromium from
being oxidized to its hexavalent form, about 99% of chromium was found in the
feces and only about 1% in the urine of these animals during the first three
days after exposure. The presumption is that the inhaled aerosols particles
were here transported by the mucociliary lift into the nasopharynx, swallowed,
and then excreted in the feces, which is fully consistent with the correlation
between chromium excretion in the feces and the self-cleansing capacity of the
lungs. Chromium absorbed from the respiratory or digestive tract in its
hexavalent form tends to bind to erythrocytes, which function as its chief
transport medium, but in its trivalent form, it is primarily bound to plasma
proteins. In the kidneys, about 60% of chromium filtered at the glomerulus is
resorbed.
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4.3 Excretion
Chromium is normally excreted through the kidneys and urine, with some
excretion through the bile and feces; minor routes of excretion include milk,
sweat, hair and nails. In oral and intravenous uptake studies, chromium is
i
excreted principally in urine. However, when chromium is administered by
inhalation or intratracheal instillation, appreciable excretion can occur in
feces. Following intravenous administration, 40% of the injected dose of
Cr(III) was excreted in the urine and 5% in the feces, and 40% of the injected
dose of Cr(VI) was excreted equally in urine and feces over a 4 day period.
In oral administration studies, as much as 80% of the Cr(VI) dose was
recovered in urine in 4 days.
Chromium (VI) causes renal tubular necrosis, probably as a result of
resorption of chromium by the tubules. With increasing time of exposure or
increasing doses of Cr(VI), there is a progressive decrease in tubular
resorption and an increase in tubular necrosis. Normal urinary loss of
chromium is approximately 0.5 to 2 pg per day, with an average urine
concentration of 1 ng/ml. In one study, workers exposed to an air
concentration of 50 ug Cr/m3 had urine chromium concentrations of 10-40
ng/ml. Among these workers, smokers had approximately twice the urinary
chromium concentration of non-smokers, perhaps due to an impaired lung
clearance capacity.
As noted in the HAD, absorbed chromium is eliminated from the body in a
rapid phase representing clearance from the blood and in a slower phase
representing clearance from tissues. Urinary excretion is the primary route
of elimination accounting for somewhat over 50% of the eliminated Cr, while
fecal excretion accounts for only 5% of the elimination from the blood. The
^^^^^^^
remaining chromium_is_deposited into deep body compartments. Limited work on
modeling the absorption and deposition of chromium indicates that adipose
-33-
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and muscle tissue retains chromium at a moderate level (~ 2 weeks), while
the liver and spleen store chromium for up to 12 months. Estimated half-lives
for whole body chromium elimination are 22 and 92 days for Cr(VI) and Cr(III),
respectively. Clearance rates of Cr(VT) and Cr(III) from the lung are not
t
well characterized for individual species. Kollmeier et al., (1985) and
others have noted an age-dependent increase of chromium lung tissue associated
with occupational (primarily inhalation) exposures, compared with chromium in
the kidney which seemed to decrease with age. As seen in the next section,
decreased phagocytic activity from elevated chromium exposures can effect the
long-term clearance of chromium from the lungs.
-34-
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5.0 TOXICOLOGY
A summary of human clinical, animal, and in vitro studies not appearing in
the 1984 HAD or revised from that document is presented in Tables 5-2, 5-3,
and 5-4. For clarity, some of the studies on respiratory effects are
i
presented in the text.
In addressing the effects on the respiratory system from exposure to
chromium exposure to Cr(III) (for which little evidence of toxicity exists)
must be separated from that of Cr(VI). Because the fumes produced from the
welding of stainless steel contain primarily Cr(VI), occupational studies can
help resolve the following respiratory effect issues:
• The degree that low level exposures to Cr(VI) irritate the upper
respiratory tract and reduce pulmonary function.
• The role of Cr(III) and (VI) in producing pneumocomosis or
fibrosis.
• The causal relationship between Cr(VI) and the onset of chronic
obstructive lung disease.
• The potential of chromium to cause lung cancer. (This issue will
be re-examined by U.S. EPA's Cancer Assessment Group.)
Initially, we want to describe the types, constituents, and amounts of
welding fumes in occupational settings. The National Institute for
Occupational Safety and Health (NIOSH) differentiates between two forms of
hexavalent chromium in airborne welding fumes: the water soluble alkali metal
and ammonium chromates, and the water insoluble chromates.
Early analytical studies indicated that Cr(VI) must be leached from the
fume or dust specimens by alkaline solutions rather than by dilute sulfuric
acid to protect Cr(VI) from reduction to Cr(III) by ferrous iron or other
reductants which may be present in the samples. The same conclusion was
reached in a interlaboratory study by Bhargava et al. (1983).
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When Blakely and Zatfea (1978) utilized milligram levels of Cr(III) salts
digested in 2% NaOH/3% NazCCh solution for 2 hours near \he boiling point,
no evidence of Cr(III) oxidation to Cr(VI) by air was observed. Ferguson
(1983) reported air oxidation o&curred, and mitigated this\ effect by
\ , \.
blanketing theN,eaching solution with nitrogen or argon gas. While Gr(III) is
oxidized easily Bv air on alkaline fusion, this is not so in alkaline
solutions despite the\favorable redox potential of chromium and excellent
stability of the resultih^ chromate ion at pH X 7. Using bulk welding fume
collected from a 308-16 stainless steel manual electrode, Zatka (1985) fouAd
\
that the air oxidation of^ Cr(III) can be prevented by hydrolytic
destabilization of the hydrox^chrornate(III) complex by the presence of
magnesium hydroxide precipitate. He reported good reproduclbility for soluble
and insoluble Cr(VI). X
Studies on the effects of chromium on defense mechanisms
have been reported. Glaser et al., (1985) conducted inhalation
exposures of sodium dichromate Cr(VI) in young rats to study the effects on
alveolar michrophages and immune functions. Sub-acute (28 days) and
sub-chronic (90 days) exposures were conducted 22 hr/day, 7 days/week to 25
and 50 ug/m3 Cr(VI) (acute) and to 25, 50, and 200 ug/m3 Cr(VI)
(sub=chronic) aerosol averaging 0.2 urn in diameter. A dose-related
accumulation of chromium occurred in the lungs, kidney, and liver, with the
lung having 30-50 times more chromium than the kidney. Similar findings have
been reported elsewhere, e.g., Kollmeier et al., (1985). Both exposures
caused an increased in phagocytic activity at 50 ug/m3 and above, at 200
ug/m3, the phagocytic activity of the alveolar macrophages decreased
significantly. Also at 200 ug/m3, the ability of the lung to clear
inhaled iron oxide particles (0.5 urn) was decreased, requiring four times as
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long to clear the Fe203 particles compared with clearance rates in control
animals.
In a similar study by Johansson et al., (1986), rabbits were exposed to
hexavalent and trivalent chromium aerosols for 4-6 weeks. Trivalent chromium
- •
concentrations were 0.6 mg/m , the hexavalent concentrations were 0.9
mg/m3 with particle size averaging about 1 urn in diameter. The number of
macrophages washed out from the lungs of rabbits exposed to Cr(VI) was
increased significantly, but not in the Cr(III) group. Under electron
microscopy, however, macrophages from the Cr(III) group "exhibited striking
morphological alterations", such as dark, chromium enriched bodies situated in
the lysosomes. Similar, but less marked, changes were seen in the Cr(VI)
group (Johansson et al., 1980, reported similar findings in earlier work).
Only the Cr(III) group produced functional changes of the macrophages, i.e.,
whereby metabolic activity (as measured by the reduction of nitroblue
tetrazolium) was increased and phagocytic activity was reduced.
Van der Wall (1985) studied the exposure of welders in Dutch industries to
total particulate, Cr, nickel and copper fume during the welding of unalloyed
stainless and high alloyed steels. He also measured the exposure to N02,
NO, and ozone. The correlation between the arc time factor and the welding
fume concentration in the breathing zone apparently was poor. MMA-welding
fumes of stainless steel contain mainly soluble hexavalent chromium. During
MIG and MMA welding, the fumes contain chromium which was insoluble in water
and not hexavalent. The dust exposure was often higher than 5 mg/m"3 in MMA
and gas-shielded arc welding. The exposure to chromium was usually higher
than 0.05 mg/m"3 for total chromium in MMA welding of stainless steel.
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Among the gaseous contaminants N02, NO, and ozone, only ozone with MIG
welding of aluminum gave concentrations in the breathing zone exceeding
0.2 mg/m"3 (0.1 ppm).
Respiratory tract irritation has been reported by numerous investigators.
i
While all of the reports agree that Cr(VI) is irritating to the nose and
respiratory tract at the levels found in the workplaces of electroplaters and
stainless steel welders, the effects from lower-level exposures are less
clear. Cohen and Kramkowski (1973) reported that 12 of 37 chrome platers had
nasal ulcers or perforations within a year of employment with exposures
averaging 7.1 ug/m3 total chrome (1.4 to 49.3 ug/m3) and 2.9 ug/m3
Cr(VI) (0.091 to 9.1 ug/m3).
The analytical procedure consisted of the following methodology:
• Membrane filters were wet ashed with distilled nitric acid and
hydrolyzed with one normal hydrochloric acid prior to analysis.
• Total chromium concentrations were determined by atomic absorption
methodologies.
• Hexavalent chromium concentrations determined by Abe11 and
Carlberg method.
• Chemical "spot test" (adapted from Feigl Method, Feigl, 1946) used
to detect the presence of hexavalent chromium on various surfaces
The authors found that 35 of the 37 workers (95%) had pathologic changes
in the mucosa and 4 out of 37 had perforation of septal mucosa. Out of the
workers who were employed less than 1 year, twelve (57%) had "more severe"
nasal pathology. For the workers employed more than 1 year, 94% had "more
severe" nasal pathology. Five workers had "chrome bites" or "chrome holes" on
the hands.
Cohen and Kramkowski concluded:
-38-
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"It is entirely possible that levels of hexavalent chrome between
0.019 and 9.1 ug/m3, as measured during this investigation,
may produce nasal damage, whereas chromic acid analyzed as total
chrome may be innocuous at much greater concentrations (i.e.,
given that a high proportion of the chromium is in the trivalent
state)."
They also noted that an extensive observation showed a profound lack of
emphasis on good industrial hygiene practice, thereby implicating direct
contact as an important route of exposure.
A subsequent study by Lucas and Kramkowski (1975) examined 11 employees of
an industrial chrome-plating facility. The concentration of Cr(VI) ranged
from 1-20 ug/m3 with a mean value of 4 ug/m3 (measured by the Abe 11
and Carlsberg method). Chemical spot tests showed widespread contamination of
Cr(VI) on "virtually all surfaces in the hard chrome area." They concluded
that the nasal and cutaneous pathology occurred from direct contact with
Cr(VI) ions, rather than through airborne exposures.
A study by Reggiani et al., (l£v) examined the correlation between
functional parameters and level of exposure, as measured by the urinary
chromium. Concentrations of chromium in the workplace air were not measured.
A total of 44 male workers from 17 plants had the following pulmonary function
tests: Vital Capacity (VC), Forced Vital Capacity (FVC), Forced Expiratory
Volume in 1 second (FEVi), Forced Expiratory Flow FEF2s-7s. The mean
urinary chromium excretion increased slightly with the consumption of tobacco,
but the difference was not significant. (Non smokers - light smokers = 7.5
ug Cr/g creatinine; heavy smokers = 9.4 ug). The multivariate analysis
showed a significant effect of chromium on spirometric values (F = 2, 27; p<
0.85). The univariate analysis showed that the effect was significant on FEV,
and FEFzs-75, but not on VC. No interaction was seen from the combination
of smoking and chromium exposure.
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To continue the investigation of subtle effects from short term exposures
to relative low chromic acid concentrations on the upper airways, Lindberg and
Hedenstierna (1983) studied 100 subjects in the chrome plating industry and
compared the results with a group of unexposed controls.
*
Eighty-five male and 19 females comprised the test group; 65 smoked. The
median exposure time was 4.5 years (range of 0.1-36 yr). Forty-three subjects
were exposed almost exclusively to chromic acid and constituted a "low
exposure" (8-hr, mean below 2 p/m3; 22 subjects) and "high exposure1 group
(2u/m3 or more; 21 subjects). Their median exposure time was 2.5 year
(range of 0.2-23.6 yr). The other 61 subjects were exposed to a mixture of
chromic acid (0.2-1.7 ug/m3) and other pollutants such as nitric,
hydrochloric, and boric acids, as well as caustic soda and nickel and copper
salts. The latter group was included to disclose any additive or synergistic
effects of chromic acid and other pollutants and was studied with regard to
lung function only. For pulmonary function measurements, the reference group
was composed of 119 auto mechanics (no car painters or welders) whose lung
function had been evaluated by identical techniques, with the same equipment,
and by the same technicians. Sixty-seven smoked, and the ages between the two
groups were comparable, mid-thirties. Nineteen office employees (13 males, 14
non-smokers) served as controls for the status of nose and throat. Their mean
age was 41 yr. (range of 26-63 yr).
Exposure levels were measured with personal air samplers and stationary
equipment. Most stationary equipment was positioned close to the baths
containing chromic acid, where the highest concentrations were expected. Air
concentrations at the various sampling stations were reported as 6-hr mean'
values.
-------
Measurements with personal air samplers were performed on 84 subjects on
13 different days. For the remaining 20 subjects, exposure was assumed to be
similar to that measured for a fellow worker doing identical work in the same
area.
*
To evaluate the variations in exposure on different days, measurements
were performed with personal air samplers on 11 subjects at three factories
during an entire work week. Air measurements were performed with stationary
equipment at five chrome baths during a total of 19 days.
Sampling was done with glass fiber filters that were leached in an
alkaline buffer solution at pH 12. After buffering to pH 4, Zephiramin was
added and the Zephiramin-Cr(VI) complex was extracted with methyl isobutyl
ketone and analyzed by atomic absorption. The limit of detection was 0.2
ug/filter, which corresponded to 0.2 ug/mj during an 8-hour sampling
period.
At mean exposures less than 2ug/m3, only 4 of 19 workers complained of
diffuse nasal symptoms. Further analysis showed that no one exposed to
concentrations below 1 ug/m3 complained of symptoms (N-9). At higher mean
air concentrations (i.e., 2 ug/m3 or more) half of the workers complained
of "constantly running nose,", "a lot to blow out"; also, in some cases an
increased frequency of nose bleeding and in a couple of cases pain in the nose
or "phlegm in the throat." The mean exposure in this group ranged between 2
and 20 ug/m3, but within this range there was no correlation between
exposure and the degree of frequency of the subjective symptoms.
A smeary and crusty septal mucosa was found in 11 of 19 workers exposed to
less than 2 ug/m3, a frequency which was higher than in controls (5/19;
P< .05). In a few exposed subjects, as well as controls, the mucosa was
diagnosed as reddened or swollen. An atrophied nasal mucosa was found in 4
subjects with low exposure to chromic acid. No subject displayed ulcerations
-41-
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or perforations. No one in the control group showed signs of atrophy,
ulcerations, or perforations.
Among the 24 employees subjected to a higher exposure to chromic acid
(i.e., a daily mean of 2ug/m3 or more), approximately one-third had a
t
reddened, smeary, or crusty nasal mucosa, but no further damage was noted.
Atrophy was seen in another 8 subjects, a frequency which was significantly
different from that for controls (0/19;P < .05). Another 8 subjects had
ulcerations in the nasal mucosa and 5 (2 of whom had ulcerations) had
perforations of the nasla septum (P< .01). The ulcerations and perforations
could not be correlated with mean exposure concentrations within the range of
the group (2-20 ug/m3). However, all 11 with ulceration and/or
perforation were temporarily exposed to at least 20 ug/m3 when working
near the baths. The period of employment in chrome plating when the
ulcerations were found were 5 months, 8 months, 3 years, 5 years, 7 years and
more than 10 years, respectively.
Non-smokers exposed to high average levels of chromic acid (2ug/m3 or
more) experienced a significant decrease in FVC and FEVi of approximately
0.2 liters and in FEFzs-7s of 0.4 liters/sec from Monday morning to
Thursday afternoon. Spirometry on Thursday morning did not significantly
differ from that on Monday morning, although mean values tended to be slightly
lower. Individuals exposed to low levels of chromic acid showed no changes
during the week. Subjects exposed to a mixture of acids, including chromic
acid in lower doses and metals, had a significant fall in FVC during the week,
but no change in the variables. No significant decrease in lung function was
seen in the reference group during the week. Among smokers, similar but
smaller changes were noted; a statistically significant change was seen only
for FVC. The differences observed between the "high," "low," and "mixed"
exposure groups of nonsmokers were less apparent in subgroups of smokers.
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Differences in lung function between exposed subjects and references were
tested after correction for the influence of age and height. This was
accomplished by computing multiple linear regression equations. For exposed
subjects and references, respectively, spirometric and nitrogen washout
t
variables were thus expressed as functions of age and height. Regression
lines for exposed subjects and references were compared by analysis of
co-variance (see Table 5-1). The authors concluded that an 8-hr mean exposure
exceeding 2 ug/m3 may cause a transient decrease in lung function, and
that short-term exposure to at least 20 ug/m3 may cause septal ulceration
and perforation.
Kilburn (1986) attempted to address the nature of respiratory functional
impairment from welding metals, including the site and extent of such
impairment and the relationship to specific exposure. His approach was to
analyze the results of studies of respiratory function in welders together
with prevalence of respiratory symptoms and to discuss the inferences which
could be made. In previous attempts to address this issue, Kilburn found that
some of the difficulty resulted from comparison of welders to other shipyard
workers, all of whom have been exposed to asbestos, and the failure to
separate the effects of cigarette smoking. Recent development of pulmonary
function values on current and ex-smokers in a stratified random sample of'the
Michigan population makes possible comparisons within smoking categories, that
is, allowance for smoking effects in occupationally exposed workers.
According to Kilburn, one of the reasons that the effects of welding may have
been under appreciated is that Forced Vital Capacity (FVC) and Forced
Expiratory Volume in one second (FEVi) have been measured to the exclusion
of Forced Expiratory Flow from 25 to 75 percent expired (FEF2S-7s) and
Forced Expiratory Flow from 75 to 85 percent expired (FEF7s-8s). It is also
evident that in welders, the recording of expiratory flow has been, in some
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TABLE 5-1
REGRESSION EQUATIONS FOR LUNG FUNCTION VARIABLES
IN THE EXPOSED AND REFERENCE GROUP
Number
of
Subjects
Function
i
R
RSD
Nonsmokers
FVC
FEVi
FEFz 5-7 s
CV%
Phase III
Exp
Ref
Exp
Ref
Exp
Ref
Exp
Ref
Exp
Ref
26
52
26
52
26
52
17
52
17
52
Y -
Y -
Y -
Y -
Y -
Y -
Y -
Y -
Y -
Y -
0.104H
0.068H
0.054H
0.039H
0.051H
0.039H
0.418A
0.315A
0.026A
0.020A
- 0.013A
- 0.022A
- 0.036A
- 0.023A
- 0.091A*
- 0.036A*
+
+
- 12.08
- 6.14
- 3.66
- 2.08
+ 16.88
- 1.45
0.42
0.88
0.17
0.81
0.81
0.62
0.81
0.55
0.74
0.42
0.81
0.68
0.73
0.21
0.61
1.00
0.59
0.85
1.08
1.44
4.87
4.44
0.40
1.32
Smokers
FVC
FEVi
FEF2S-7s
CV%
Phase III
Exp
Ref
Exp
Ref
Exp
Ref
Exp
Ref
Exp
Ref
48
67
48
67
48
67
24
67
24
67
Y -
Y -
Y -
Y -
Y -
Y -
Y -
Y -
Y -
Y -
0.070H
0.093H
0.053H
0.069H
0.034H
0.043H
- 0.025A
- 0.037A
- 0.033A
- 0.032A
- 0.063A
- 0.042A
0.411A
0.313A
0.032A
0.022A
- 5.96
- 9.87
- 3.63
- 7.04
+ 0.89
- 2.99
+ 0.11
+ 2.89
+ 0.29
+ 0.67
0.65
0.77
0.75
0.66
0.70
0.41
0.70
0.50
0.45
0.36
0.70
0.66
0.57
0.70
0.99
1.23
5.86
4.81
0.90
0.51
NOTE: When statistically significant, height has been included in equations,
A = Age (yr).
H = Height.
RSD = Residual standard deviation.
*Difference between exposed and references significant (P, < .05).
Source: Lindberg et al, 1983.
-44-
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cases, stopped before completion of expiration, resulting in an incomplete FVC
and that this early termination has produced artificially high air flow values
together with FEVi/FEV ratios above 80%. Furthermore, a sensitive
technique, which is to observe changes in flow rates across a workshift in
i
each worker has not been applied to welders.
Kilburn's study, which began in 1981 and did not include exposure levels,
was designed to determine the baseline pulmonary function of welders compared
with a nonshipyard, non-Los Angeles comparison group, and to measure the cross
shift changes in respiratory function in those welding aluminum, stainless
steel, and mild steel. The study was designed to interview each welder
briefly and measure his FVC and flow rates before he went to work on a Monday
morning. After a full workshift, each welder returned to the field laboratory
for a second measurement of FVC and flow rates together with a diary of
welding exposure during the day, including metal used, rods, type of welding
and surface coating materials and protective equipment. A respiratory
questionnaire and a questionnaire for cross shift symptoms was completed by
the welder with the assistance of the field staff to define standard
bronchitis, wheezing and shortness of breath. (Questions were those of the
British Medical Research Center questionnaire as adopted by DLD-78.) He also
inquired about pneumonia, respiratory illnesses, time lost from work, chest
pain, pressure or heaviness. The inventory of symptoms experienced during the
work shift included feverishness, chills, thirst, fatigue, headaches, muscle
aches, metallic taste, hoarseness, sore throat and chest tightness. This
constitutes the symptom list for metal fume fever.
Spirograms were recorded on either an Ohio rolling seal spirometer or on
Stead-Wells spirometers. These were calibrated repeatedly with a large
syringe during the study. Measurements were made with the subject standing.
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wearing a nose clip and following the American Thoracic Society criteria for
FVC, FEVi, FEF2S-7s and FEF7s-ss.
The welders were equally distributed among those who had never smoked
cigarettes, 73, and those who had smoked, 75. The symptoms were compared to
f
the stratified random sample of Michigan men in a smoking specific manner.
Cross shift symptoms were compared to 29 hospital employees with a similar age
and ethnic and smoking composition, all of which were men.
In nonsmokers, the prevalence of phlegm production was seven fold greater
than Michigan men, and it was increased further in ex- and current smokers,
33.9% in the latter. Shortness of breath on climbing two flights (40 steps)
was also much increased and was highest in nonsmokers. Wheezing was also
increased and showed a very slight smoking gradient for increase from
nonsmokers to current smokers. Chest heaviness was the msot frequent symptom
and occurred in 38% to 47% of the welders.
For symptoms during welding, cough and sputum were approximately twice as
frequent, chest tightness occurred in up to 25% compared to none in controls,
and wheezing ranged from 5% to 21% and only 4% in controls. Palpitations and
the symptoms of metal fever (fever, muscle ache, metallic tastes) were also
greatly increased.
For pulmonary function measurements, the nonsmokers had significant
reductions in FVC (4.3%), FEV, (9%), FEF2S-7s (4.4%) and in FEF7S-8S
(14.4%). The current smokers were more abnormal even though compared
specifically to the Michigan smokers. These large reductions in FVC
effectively confounded the slow (effort independent) portion of the expiratory
flow and brought the mid and terminal flow FEF2s-7s and FEF7S-8s to normal.
In order to make the cross shift comparisons of function, any welder who
worked for an hour or more on stainless steel belonged to that group and an
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hour or more on aluminum to be an aluminum welder. Very few of the cohort
worked entire shifts on either stainless steel or aluminum. A very small
number worked on both. The aluminum welding had little effect on FEFi or
FVC. The welding of mild or black steel caused a small decrease in nonsmokers
but an increase of 50 ml in FVC and 80 ml in FEVi in smokers. When
nonsmokers welded stainless steel they had slightly greater decreases in
FEVi and FVC than when nonsmokers welded mild steel. However, when the
smokers welded stainless steel, they had decreases of 130 ml in FEVi and 110
ml in FVC. These contrasted with net increases for when the smokers welded
mild steel and, in effect, doubled the cross shift difference.
To Kilburn, it appeared that smokers were more susceptible to fumes of
stainless steel welding containing hexavalent chromium than were nonsmokers
and that the smokers cross-shift decreases were greater than those of smokers
welding mild steel, who improve cross shift. These sizeable differences, as
group means, suggest a specific adverse effect from stainless steel fumes
which would be attributed to hexavalent chromium.
-47-
-------
TABLE 5-2
SUMMARY OF STUDIES ON HUMAN EXPOSURES TO CHROMIUM COMPOUNDS
l
£>
00
Route of
Exposure
Inhalation
Inhalation
Inhalation
Compound/ Analytical Occupation
Oxidation Method
State
Cr Atomic Catalyst
Cr(VI) Absorption Plant worker
Spectrometry at 2 plants
and Colorimetric
Spectrophotomety
for Cr(VI)
Cr NIOSH method Farm machinery
Cr(VI) #319 for Cr(VI) painters/
(lead coaters
chroma te) NIOSH method
#173 to determine
total chromium or
chronlum metal .
Cr Atomic 97 Silicon
Cr(VI) Absorption steel rollers
or conductivity
Coupled Plasma-
Atomic Emission
Spectroscopy
for Cr. For
Cr(VI)-Colormetric
Concentration Duration of
of Chromium Exposure
Cr =
37 - ,,g/m3
Cr(VI) = 0.8 - 4.2
u/m3
Cr =
L0.004 - 0.429
mg/m3
Cr(VI) = 0.001 - 0.742
mg/m3
Cr = ND-0.2mg/m3 Up to 10 hrs/day
40 hrs/week
Cr(VI)=0 8-1.8ng/mj
Author's findings/
Statistical
Significance
69% + 72% of employers
reported 1 or more symtoms
(cough, nasal sores, skin
rashes.)
For the painter job. 85%
of the measurements
exceeded the NIOSH
recommended exposure limit
of 0.001 mg/m3 or Cr(VI).
An measurements of the
8-TMA's for total Cr were
below the OSHA PEL of
lmg/m3 for metal and
insoluble Cr salts.
Only 1 area sample of Cr(VI)
exceeds NIOSH standards.
for term of employment
(machine grinding operation
in the slapboard). *Total
Cr levels were within the
ACG1H and OSHA standards.
41-43% had mucosal symtoms.
43% recurrent cough and 23%
chronic bronchitis. Eye and
nasal irritation were
Reference
Zey and Lucas
1985
Bloom and Pequese
1985
Stephenson and
Cherniak 1984
statistically associated with
Direct contact
vs Inhalation
Chromic acid Abell and Electroplaters
Carlberg
Cr(VI) Average duration
<0.001 mg/m3 - of employment
0.020 mg/m3 9 years. 4 months
(0.004 mg/m3
mean value)
work in a dustier job. P<0.
Cr(Vl) was within acceptable
limits yet widespread
author believes that direct
contact with the Cr(VI)
chromate lyn (vs.
inhalation) is the cause of
OS)
Lucas et al
1975
nasal and cutaneous pathology.
-------
TABLE 5-2 (Cont.)
SUMMARY OF STUDIES ON HUMAN EXPOSURES TO CHROMIUM COMPOUNDS
Route of Compound/
Exposure Oxidation
State
Inhalation Water
soluable
Cr(VI)
Inhalation chromic
acid
i Inhalation Cr in high
£ nickel alloy
i welding
Inhalation Chromic
acid
Analytical Occupation
Method
Sodium Carbonate welders
Solution
Scanning electron
microscopy.
Atomic Chrome plating
Absorption plant workers
spectrophotometry
Electrothermal welders
Atomic
Absorption
N/A Chrome plating
plant workers
Concentration
of Chromium
MMA/ss 0.2mg/m3
MIG/ss 0 lmg/m3
(average)
0.05 ug/m3
46 ,,g/m3
0 10 mg/m3
average
0 18-1 .4
mg/m3
Duration of
Exposure
5.8 hr/day
17 years =
median total
welding time
Employment
ranged from
2 weeks to 1 year
Author's findings/
Statistical
Significance
Cr(VI) exhibits fibrogenic
potential
Investigation of work
places showed that 3 of
16 chrome plating balhs
exceeded the sanitary limit
of 20 ug/m3.
Welding of high nickel
alloy causes more symtoms
in the respiratory tract
than ordinary stainless
steel welding.
(p<0.006)
Chromic acid is the agent
responsible for the.
ulcerated nasal sep'ta among
Reference
Stern et al
1983
Lindberg et al
1985
Akesson and
Skerfving
1985
Klienfield and
Rosso
1965
7 workers affected (and
perforation in 4 of these)-
out of 9 workers examined.
Inhalation Cr
Neution
Activation
Analysis
Copper smelter
workers
27-31 years (p = 0.001)
A four-fold increase of
chromium in lung tissue
Gerhardsson
et al
1984
was found for smelter
workers' compared to
controls.
The concentration of Cr did
not decline with time after
exposure had ended; indicating
a long biological half-time.
-------
TABLE 5-2 (Cont.)
SUMMARY OF STUDIES ON HUMAN EXPOSURES TO CHROMIUM COMPOUNDS
Route of
Exposure
Inhalation
Compound/ Analytical
Oxidation Method
State
Chromium
oxide
Analytical Concentration
of Chromium
Spray-painters 0.005-0 008
mg/m3
(TLV=0 05 mg/m3
Duration of
Exposure
Employed
1-26 years
Author's findings/
Statistical
Significance
Histological changes in
the exposed group are
signif icantlly higher than
that of the non-industrial
control group (p<0.01).
Reference
Hellquist et al
1983
I
Ul
o
Although exposure values
were well below TLV.
histopathological changes
and clinical symptoms had
developed.
Inhalation Cr Atomic
Absorption
Speatrometry
and Neutron
Activation
analysis
Inhalation Cr(VI) Air samples
collected by
high volume
samples and
midget impirgers
Inhalation FeO- Atomic
Cr20j Absorption
NaCrOa Spectropnoto-
CrOs metry
K2Cr20«
Lungs of
6 individuals
Cr chemical
production
workers. From
1945 1949
Chromate
factory
workers
(10 of the 11
were heavy
smokers)
413 ng/m3
averages
during 1945-49
Cr(III) content in
lungs ranged
from 13.9 to
2.368.43
ii9/9 dry tissue
(489.79 i,g/g
average)
lifetime Accumulated dust in the Vanoeteren et al
lungs of ordinary persons 1982
contain significant levels
of Cr. Approximately 0.329
119/9
13 years or more estimates of exposure Braver et al
at 52 ug/m3 levels at which increased 1985
4Cr(VI) or cancer risk occured/
100 ng/m3 of suggest potential excess
lung cancer risk from
exposure to 52 ng/m3.
the current OSHA standard
for Cr(VI).
23.9 years 7 had perforation of the Nishiyama
average nasal septom. 8 had 1985
term of employment squamous cell carcinomas.
3 had small cell carcen-
omas.
Chromate carcinogenesis
cannot be explained simply
by lung Cr content or duration
of exposure.
-------
TABLE 5-2 (Cont.)
SUMMARY OF STUDIES ON HUMAN EXPOSURES TO CHROMIUM COMPOUNDS
Route of
Exposure
Compound/
Oxidation
State
Analytical
Method
Occupation Concentration
of Chromium
Duration of
Exposure
Author's findings/
Statistical
Significance
Reference
Inhalation
Chrome mist
Statistical
sign determined
by chi-square
and Fisher exact
test
Die-casting and
electroplating
plant workers
Little data
available in
1978 airborne Cr
acid levels were less
than PEL of OSHA
(100 ,,9/m')
1959 breathing rone
sample was sx the
Current PEL
At least 10 years
of credited
pension service
The proportional mortality
analysis demonstrated a
statistically significant
excess of total cancer
deaths.
(PMR = 1.27. p<0.00l)
Silverstein'et al
1981
CrOs Chromeplating
workers:
(116 "hard"
62 "bright")
CrOa our concen- 1 year +
tration average
= 7,,g/m:i
(range=l- 12 ug/m3)
near middle of room
Most deaths from cancer Franchini et al
occurred among hard Cr 1983
platers, the excess against
the expected rate being
statistically significant
(7 observed, 2.7 expected.
p=0.02) All deaths from
lung cancer occurred in this
subcohort (3 observed, 0.7
expected, p=0.03). Increased
mortality from cancer among
Cr platers seems to be related
to exposure intensity.
Inhalation X-ray Chronate
microanalyser worker
and scanning (cigarette
electron micro- smoker)
scope for Cr
particles in lungs
Atomic absorption
measured Cr
content in other
organs.
Cr content in 35 years
lungs was 90x that
in normal lungs
(2 60-36 67,,g/g)
(normal - 1 17(lg/g)
Autopsy performed
7 hours after death
Cr concentration
in tumor tissue of
Cr induced pulmonary cancer
Nasal septum perforation
Differentialed squamous
cell carcinoma
Kim et al
1985
lung was also high
at 23 30 (Jg/g
-------
TABLE 5-2 (Cont.)
SUMMARY OF STUDIES ON HUMAN EXPOSURES TO CHROMIUM COMPOUNDS
Route of
Exposure
Compound/
Oxidation
State
Analytical
Method
Occupation Concentration
of Chromium
Duration of
Exposure
Author's findings/
Statistical
Significance
Reference
Inhalation
welders
2-10 mg/m3
17 year average
occupational
experience
Of 22 epidemiological Stern
studies of cancer incidence 1983
among welding populations.
17 report more than 3 cases
of lung cancer. 16 of the
22 cases based on 600,000
man-years of observation.
Welders are at excess risk
due to their occupation.
tsj
I
Inhalation Cr
Cr(VI)
Inhalation Chromic
and Direct acid
Contact
Inhalation and Chromic
Direct acid
Contact
Inhalation Chromic
acid
NIOSH method Welders total Cr
P 6 CAM 173. 0.02 mg/m3
for Cr. NIOSH Cr(VI):
method P & CAM 0 0006 mg/m3
169 for Cr(VI)
Atomic Electroplaters mean total chrome
Absorption 0 0071 mg/m3
for Cr
Abell and Carlson
for Cr(VI)
Chrome Plating
worker
104 workers 0.2 - 20+ug/m1
exposed to
chrome plating
16.8 average
years, working
as welder
2 days rash
development
3-5 months
Exposure time
correlated with
age of the subject
(r:0.65)
Significant excess
prevalence of cardio-
vascular disease and
a significant increased
prevalance of some res-
piratory symtoms (productive
cough) among workers.
Association between length
of employment and develop-
ment of increasingly severe
nasal pathology is.
significantly positive
(p = .01)
Specified allergic
asthma due to chrome
sensitization
Nasal septal ulceration
and perforation seen in
2/3 of subjects exposed
to 20 of ug/m3 or
more for a short term.
Johnson and
Milius
1980
Cohen and
Kramkowski
1974
Joules
1932
Lindberg and
Hedenstierna
1983
An 8 hour mean exposure
above 2ug/m3 may
cause a transient decrease
in lung function.
-------
-53-
-------
TABLE 5-2 (Cont.)
SUMMARY OF STUDIES ON HUMAN EXPOSURES TO CHROMIUM COMPOUNDS
Route of
Exposure
Compound/
Oxidation
State
Analytical
Method
Occupation
Concentration
of Chromium
Duration of
Exposure
Author's findings/
Statistical
Significance
Reference
Direct Contact Cr(VI)
Applications of sodium
dithlonlte applied to skin
(Na2S204) to areas
of the skin exposed to
Cr(VI) offers an accept-
able alternative to the
ferrous sulfate approach.
Sodium dlthtonite converts
Cr(VI) to Cr(III).
Wall
1982
Uniary Multi-element 11 healthy
Excretion argon-plasma male adults
(as a trace emissions systems
element) of
Chr omnium in
Men
Inhalation Cr(VI) Plating
as chromic workers
acid
Inhalation Cr(VI) Atomic Stainless
Absorption steel
Spectrometry welders
3 hour urine Group mean on 24 hour Kanabrocki et al
specimens over time scale ranged from 1983
27 hours 2.3*l.lug/3 hours.
(p<0.02) 151% Increase
statistically significant
circadian rhythm.
Significantly Increased Stella et al
SCE frequencies 1982
(p<0.001)
Average Cr level: mean: No statistically Llttonn et al
81|,g/m3 19 years significant differences 1983
were observed as to
Urine: frequency of cells with:
47 i/no 1 /mo 1 breaks and fragments; gaps
creatinine and isogaps; interchanges,
dicentncs, lungs, and
makers total number of cells
with structural abberations;
hypordlploidy; no differences
in the frequencies of
micronuclear or SCE'S in
lymphocytes of peripheral
blood.
-------
TABLE 5-2 (Cont )
SUMMARY OF STUDIES ON HUMAN EXPOSURES TO CHROMIUM COMPOUNDS
Route of
Exposure
Inhalation
Compound/
Oxidation
State
Analytical
Method
Electrothermal
Atomic
Absorption
Occupation
53 Stainless
Steel welders
(20 smokers)
Concentration
of Chromium
Air
Mean
^Oug/ni1
tned i an
Duration of
Exposure
Mean:
03 years
Author's findings/
Statistical
Significance
Air concentration of total
Cr showed a linear
relationship to post-shift
urine concentration
(r - 0.72. p<0.001)
Reference
Tamino et al
1981
Urine.
Mean
121 ,,q/ml
median
32 ng/l
I
Ul
Ul
I
Inhalation
Flameless
Atomic
Absorption
Spectrometry
Tannery
workers
Tendency for smokers to
have higher urine con-
concentrations.
No relationship between
welding years and Cr
urine concentrations. But,
results show that current
and previous exposure con-
tribute to urinary Cr. A
single urinary Cr measure-
ment is not exact. But
urine measurements can be
used to estimate airborne
exposure.
Urinary Cr, Cr/Creatinine Saner et al
ratio, daily Cr excretion, 1984
and hair Cr concentrations
were significally higher
and urinary Bj- micjro-
globulin/Crevatics sig-
nificantlly lower in both
tannery workers and control.
A significant negalme cor-
relation was found between
urinary 82- microglobulin/
Cre and Cr/Cre ratios of
tannery workers and controls.
(p<0.02)
No correlations between dur-
ation of exposure to Cr, and
hair and urinary Cr.
-------
TABLE 5-2 (Cont )
SUMMARY OF STUDIES ON HUMAN EXPOSURES TO CHROMIUM COMPOUNDS
Route of
Exposure
Inhalation and
Dermal Uptake
Inhalation
Compound/
Oxidation
State
Cr(VI)
Cr
Analytical
Method
Electrothermal
Atomic
Absorption
spec trome try
Direct
Flameless
Atomic absorption
Occupation Concentration
of Chromium
8 Chromeplaters < 2 n9/m3
Manual metal
arc stainless
steel welders
Duration of
Exposure
urine samples
collected during
a period of Sd.
mean exposure
time1 20 years
Author's findings/
Statistical
Significance
Urine Cr increased from
Monday morning to Tuesday
after noon and then re-
mained constant for the
rest of the work week.
(P = 0.71)
Welders had far higher
levels of Cr in urine
than individually
Reference
Lindberg and
Vesterberg
1983
Littorin et al .
1984
Inhalation
Cr in urine
Spectrophoto-
metric
Stainless
Steel
Welders
mean exposure
time- 20 years
range. 7-41 years
matched controls,
both in morning and
afternoon. However.
there were no signs
of kidney damage in
tests. (p<0.001)
Results show a slow
and fast compartment
for Cr.
Slow = lid to infinity
Fast = 4-35 h.
Significant correlation
(p
-------
TABLE 5-2 (Cont.)
SUMMARY OF STUDIES ON HUMAN EXPOSURES TO CHROMIUM COMPOUNDS
Route Of
E
-------
TABLE 5-2 (Cont )
SUMMARY OF STUDIES ON HUMAN EXPOSURES TO CHROMIUM COMPOUNDS
Route of
Exposure
Dermal
(Patch Test)
Compound/ Analytical
Oxidation Method
State
potassium
dichromate
Occupation Concentration
oT Chromium
healthy adult 0 5*.
volunterrs
Duration of Author's findings/
Exposure Statistical
Significance
2 days Most of the positive
reactions occurred
in the group with
present occupational
exposure to Cr.
Reference
Peltonen
and Fraki
1983
Inhalation
Cr/Cr(VI)
atomic
absorption
spcctrophoto-
meter
MMA Stainless
Steel welders
Personal air
samples
5 1 nig/in'
total pn Heal
(3 V? Ci )
(35-" Ci (VI)/Cr)
03
I
Among the remaining test
population, sensitivity
to dichiornate was rare.
mean time as Use of Cr and Ni urinary
welders analysis as indices of
short-term exposure is
13 years not as dependable as pre-
(50+6) viously assumed.
The Cr and Ni concentra-
tions in whole blood and
plasma did not correlate
with the measured exposure
but the daily mean increase
in the Cr concentration
reflected exposure to Cr
and Cr(VI) very well.
Retention rate of magnetic
dust in lungs correlated
well (p<0.0!) with the
daily mean increase of Cr in
blood. Good correlations
(p<0.000) found between the
retention rate of magnetic
dust and the personel air
samples of Cr and Cr(VI).
Rahkonen et al
1983
-------
TABLE 5-2 (Cont )
SUMMARY OF STUDIES ON HUMAN EXPOSURES TO CHROMIUM COMPOUNDS
Route of
Exposure
Inhalation
Compound/ Analytical Occupation Concentration
Oxidation Method of Chromium
State
atomic workers 7-122IMP/I"1
absorption exposed to
spectroscopy Chromium
electrothermal
method
NIOSH method
P&CAM 319
for Cr(VI)
Duration of Author's findings/ Reference
Exposure Statistical
Significance
End-of -shift urinary Mutti et at
chromium and its 1984
increase above pre-
exposure levels were
closely related to the
i concentration of water
soluble Cr(VI) in workers
exposed to water insoluble
chromates or to water
soluble chromic1 sulfate
was, definately higher than
that observed in subjects
not occupationally exposed
to Cr compounds; but it
cannot be recommended as
short-term exposure test
for evaluation of the job-
related hazard.
Inhalation
(Direct
Contact)
Chromic
acid
Abell and
Carlberg
Hard chrome
platers
liiq-20|.g/m1
2 day evaluation
8 hour workday
40 hour week
Ave. duration
and employment
7 1/2 years
Much nasal and cutaneous
pathology from direct
contact with Cr(VI).
Questions the
protectiveness of NIOSH
standards. Difficult to
related nasal pathology to
inhalation of Cr.
tucas and
Kramkoski
1975
Inahalation
Cr(III)
shipyard
welders
0 003-0 05
mgm/m'
Total fumes in welder's
breathing zone exceeded
threshold limit value
(13 cng/m3) when local
until after system was
shut down.
Bell
1976
Inhalation
Chromium
containing
dust
(Cr203FeO)
Chromite miners
8 1/2 - 18 years
mining service
Pneumonocis in chromite
chromite miners is due
to the deposition of
radio-opaque chromite
dust in the tissues.
The condition is benign
and does not cause
fibrosis.
Sluis-Cremer and
DoToit
1968
-------
TABLE 5-2 (Conl )
SUMMARY OF STUDIES ON HUMAN EXPOSURES TO CHROMIUM COMPOUNDS
Route of
Exposure
Compound/
Oxidation
State
Analytical
Method
Occupation Concent rnli on
of Chromium
Duration of
Exposure
Author's findings/
Statistical
Significance
Reference
Inhalation
Chromium
(electro-
plating)
Chrome plating
workers
i,g Cr/q Creatimne
(urinary) <6 to >15
p<0.05
Dynamic values of
spirometry (FeVi and
FeFj5-75) ARC LOWER AMONG
the workers with higher
urinary chromium. No
observed effect of chromium
on VC.
Electroplate workers
(esp. hard) are at risk
in developing obstructive
respiratory syndrome.
Bovet et al
1977
o
Inhalation
Cr03
Chrome and
ferrochromc
workers
0 001 -
0 583 mg/m3
Pulmonary disease of
occupational origin
found in 4 medical
Princi
1962
et al
cases. It is characterized
by: acute pheumomtis.
cough, wheezing, anerexia,
loss of weight, increased
sedimentation rate, linear
and modular fibrosis in
the chest. Roentgenograns,
ventilatory impairment, and
is associated with exposure
to high concentrations of
metallic silicide.
Inhalation Chromic
acid
solution
workers using 5V. Chromic Acid 2 weeks
Chromic acid solution
anod i z i ng
operations
Anterior nasal ulceration
in 50-60% of the cases
and found in workers not
initially associated with
the tanks, in an
atmosphere higher than
safe concentrations of
Cr acid fumes.
Zvaifler
1944
Larger ulcerations (deeper
and reaches the cartilage)
were found in workers who
work on the tanks or are in
intimate contact with the
fumes (35%). 5-10% have
something similar to atrophic
rhinitis.
-------
TABLE 5-2 (Cont )
SUMMARY OF STUDIES ON HUMAN EXPOSURES TO CHROMIUM COMPOUNDS
Route of
Exposure
Inhalation
Compound/
Oxidation
State
Chromic
acid
Analytical
Method
lodometric
method
Species/
Strain
Chromium
platers
Concentration
oT Chromium
0- 55 7
mq/IO m1
Duration of
Exposure
l week to 3 years
Author's findings/
Statistical
Significance
16% had perforated
nasal septa.
21% ulcerated septa
Reference
Bloomfield and
Blum
1928
Inhalation
Chromic
acid
Chromium
workers
47% mucosa inflamation
58% nosebleeds
43% chrom holes on hands
Proper ventilation and
sanitary measures needed.
original c«.haust
system
0 09 - I 2 mq/m1
revised c-haust
system
nog
New ventilation system
was needed to prevent
chromic acid injuries
Gresh et al
1944
Case reports on Chrornate
lung cancer
Letterer et al
1944
Inhalation
Various
Chromium
compounds
Chromium
producing
plant
(available data)
0 01 - 21 0
mg/m3
4-47 years
of employment
42 deaths from cancer
of the respiratory
system.
21% of all deaths
63% of all deaths
from cancer.
Machle and
Gregorius
1948
-------
TABLE 5-3
ANIMAL STUDIES ON CHROMIUM DISPOSITION. PHARMACOKINETICS. AND EFFECTS
Route of
Exposure
Inhalation
Inhalation
exposure to
Compound/
Oxidation
State
Cr in MMA/SS
and MIG/SS
welding
3-10%
(water
soluble
hcxavalent ,
alkaline
chroma tes)
Analytical Species/ Concentration
Method Strain of Chromium
Neutron rats/Wistar 164 i,g/mj
activation maximum inhaled
analysis
and AA
Cr(VI) tCr(III) atomic rats/Spraque-
Suzuki et al
aerosots absorption Dawley mg/m1
Duration of
Exposure
1 hour/day for
1. 2, 3, and 4
weeks
7 1-15.9
6 hours
Author's findings/ Reference
Statistical
Significance
p<0.00i Linear retention Kalliomaki et al .
of Cr in lungs. 1983
Slow clearance mechanism.
Lungs are the main target
organ of inhaled chromium.
The water soluable hexa-
valent alkaline chroma tes
are chemically transferred
into insoluble Cr compounds
in the respiratory tract.
2 hours 8 died after
Cr(VI) (severe asthmatic 1984
KJ
I
spcctrophoto-
meler.
symptoms). No deaths
after Cr(III) exposure.
Cr(VI) exposure caused
weight loss.
Cr(VI) is transported from
lungs to blood (more
rapidly than Cr(III)) and
taken up by erythroc,ytes
and viscerol organs.
Inhalation
Cr
X-ray bovine
fluorescence lungs
spectroscopy and (buffalo)
scanning electron
microscopy
Animals inhabiting mining
and industrial complexes
can accomulate large
amounts of particulate
matter with absorbed heavy
metals in their lungs.
Dogra et al
1984
Inhalation
Chromium
in MIG/SS
MMA/SS
welding
fumes
Neutron
activation
analysis
rats/Wistar MMA. 2 4-7%
of welding fumes
MMG. 4-15% Of
fumes
1 hour/day
for 1 , 2, 3 and
4 weeks
Cr accumulation on
lungs was very high.
It cleared with the
half-time of 240d.
for MIG/SS (insoluable
form of Cr) 40d for MMA/SS.
Kalliomaki
1983
et al
-------
TABLE 5-3 (Cont )
ANIMAL STUDIES ON CHROMIUM DISPOSITION. PHARMACOKINETICS, AND EFFECTS
Route of Compound/
Exposure Oxidation
State
Intratiacheal Cr(VI)
Administration (sodium
chromate)
Cr(III)
(chromium
chloride)
Inhalation Cr in
MMA/SS
welding
, fumes
C* (95% Of
Y which is
water-
soluble
hexavalent
alakal me
chromates:
CaCrO erated by reduction of Cr(VI).
Study suggests that the low-
molecular-weight components
should be involved in the
passage of this element from
the lung to the other tissues.
rats/Uister 3 6"; of 10 hour Lung Cr rentention rate = Kalliomaki et al
13 mg/m3 maximum 1 9 ng/hour. The re- 1982
(tot.il welding time) tent ion in lungs was
linear (p<0.00l)
Kidney Cr retention
- 0.10 ,,g/n
Liver Cr retention
= 0 19 ,,g/h
Blood Cr retention
= 0.47 ,,g/h
Blood Cr concentration
correlated well (p<0.001)
with the cumulative .exposure
time, water-soluble hexa-
valent alkaline chromates
seem to undergo chemical
transactions into insoluble
Cr compounds in the res-
piratory tract.
rabbits/ o s - o 5 mg 0-240 minutes Cr(vi) may enter the blood Weigand et al
New Zealand unreduced via the lung and 1984
white is partly deposited in cells
over a prolonged period of
time.
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TABLE 5-3 (Cont )
ANIMAL STUDIES ON CHROMIUM DISPOSITION. PHARMACOKINETICS, AND EFFECTS
Route of
Exposure
Inhalation
Compound/
Oxidation
State
CrClj
Analytical
Method
atomic
absorption
spectrometry
Species/
Strain
rats/SD
Concentration
oT Chromium
13 3 mg/m3
particle size
<2if«
Duration of
Exposure
5 hours
Author's findings/
Statistical
Significance
Total Cr contents in lungs
were 8-25% higher than
those in liver.
Reference
Wada et
1983
al
Statistically significant
correlation btween LMCR
in the lungs and each of
Cr-HMW (high-molecular-
weight) LMCR and total
Cr contents in the liver.
LMCR in lungs is in
equilibrium with Cr in the
rest of the body.
-------
TABLE 5-3 (Cont )
ANIMAL STUDIES ON CHROMIUM DISPOSITION, PHARMACOKINETICS. AND EFFECTS
Route of
Exposure
Subcutaneous
Injection
Compound/ Analytical
Oxidation Method
State
Cr(III)
extracted
From 5g of
leather
Species/
Strain
various
tests
performed
Concentration
of Chromium
0 08 - 0 78
mg/ml
Duration of Author's findings/
Exposure Statistical
Significance
All leather glove extracts
caused a reaction in the
skin irritation test by
the subcutaneous injection
Reference
Naruse et
1982
al
method. The causes of the
irritation were the low pH
and chromium sulfate of the
leather glove extract.
Contact dermatitis was the
result.
Injection
potassium
dichromate
mice
1. 5. or 10 mg/
kg body wciqht
Single i p
injection
ui
l
Lowest effective dose
of hexavalent chromate
for micronuclei induction
in mouse bone marrow is
1/50 of that reported
previously
[Fabry (1980)]
Chromosmal damage resulting
by induction of micronucle
in bone marrow cells.
Paschin and
Toropzev
1982
Injection
atomic
absorption
spcctrometry
mice
15 mq/kq
single i.p.
Highest concentrations of
Cr are found in the soluble
fraction of liver.
Binding substances for Cr
are mainly a low-molecular-
weight compound, which
decrease more rapidly in the
liver soluble fraction than
the H-M-W.
Suzuki and Wada
1982
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TABLE 5-3 (Conl )
ANIMAL STUDIES ON CHROMIUM DISPOSITION. PHARMACOKINETICS, AND EFFECTS
Route of
Exposure
Injection
Compound/
Oxidation
State
sodium
di chroma te
Cr(III)
chloride
Analytical
Method
electrothermal
atomic
absorption
spcctroscopy
Species/
Strain
rats/male
Spraque-Dawley
Concentration
oT Chromium
20 mg/kq
80 Illq/kq
Duration of Author's findings/
Exposure Statistical
Significance
Chromium entered liver and
kidney tissues at a slower
rate after injection of
Cr(III) chloride than after
sodium dichromate.
Reference
Cupo and
Wetteshahn
1985
[Noted that the
natural levels of
iron did not alter
the AA readings. ]
However, Cr(III) did not pene-
tration liver and kidney cells
and was slowly bound to both
RNP and chromatin.
I P. Injection
sodium
dichromate
chromic
chloride
rat/male
Spraque-Dawley
20 01" 40 mq/kg
HO mg/kq
Cr(VI) rapidly induced
significant levels of
cross-linking in rat
kidney, liver, and lung.
DNA-protein cross-links
Tsapakos et
1983
al
persisted 36 to 40 hours
after injection in rat
kidney and lung yet had
been repaired in liver
by 36h. Data suggests
lung and kidney are more
sensitive than lines to
Cr-induced DNA damage.
I.v.
Injection
Cr(VI) as
(Nai'CrzO?)
Cr(III) as
(CrClj)
autoradio-
gr.tphic
Spectrophoto-
mctric
mice/C57BL
5ng/kq body
weight
1, 1, 24 hours
Embryonic and fetal
uptake of Cr(VI) was about
I Ox higher than that
of Cr(III).
The ratioactivity after
administration of
Cr(VI) may represent Cr(III)
after reduction in the
tissues.
Danielsson et al
1982
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