EPA-540/1-86-019
Office of Emergency and
Remedial Response
Washington DC 20460
Off'ce of Research and Development
Office of Health and Environmental
Assessment
Environmental Criteria and
Assessment Office
Cincinnati OH 45268
Superfund
xvEPA
HEALTH EFFECTS ASSESSMENT
FOR HEXAVALENT CHROMIUM
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EPA/540/1-86-019
September 1984
f
HEALTH EFFECTS ASSESSMENT
FOR HEXAVALENT CHROMIUM
VJ
U.S. Environmental Protection Agency
Office of Research and Development
Office of Health and Environmental Assessment
Environmental Criteria and Assessment Office
Cincinnati, OH 45268
U.S. Environmental Protection Agency
Office of Emergency and Remedial Response
Office of Solid Waste and Emergency Response
Washington, DC 20460
U.S. Environmental Protection Agency
Region 5, Library (PL-12J)
77 West Jackson Boulevard, 12th Floor
Chicago, IL 60604-3590
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DISCLAIMER
This report has been funded wholly or 1n part by the United States
Environmental Protection Agency under Contract No. 68-03-3112 to Syracuse
Research Corporation. It has been subject to the Agency's peer and adminis-
trative review, and 1t has been approved for publication as an EPA document.
Mention of trade names or commercial products does not constitute endorse-
ment or recommendation for use.
11
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PREFACE
This report summarizes and evaluates Information relevant to a prelimi-
nary Interim assessment of adverse health effects associated with hexavalent
chromium. All estimates of acceptable Intakes and carcinogenic potency
presented In this document should be considered as preliminary and reflect
limited resources allocated to this project. Pertinent toxlcologlc and
environmental data were located through on-Hne literature searches of the
Chemical Abstracts, TOXLINE, CANCERLINE and the CHEMFATE/DATALOG data bases.
The basic literature searched supporting this document 1s current up to
September, 1984. Secondary sources of Information have also been relied
upon 1n the preparation of this report and represent large-scale health
assessment efforts that entail extensive peer and Agency review. The
following Office of Health and Environmental Assessment (OHEA) sources have
been extensively utilized:
U.S. EPA. 1980b. Ambient Water Quality Criteria for Chromium.
Environmental Criteria and Assessment Office, Cincinnati, OH. EPA
440/5-80-035. NTIS PB 81-117467.
U.S. EPA. 1983a. Reportable Quantity Document for Chromium (and
Compounds). Prepared by the Environmental Criteria and Assessment
Office, Cincinnati, OH, OHEA for the Office of Solid Waste and
Emergency Response, Washington, DC.
U.S. EPA. 1984. Health Assessment Document for Chromium.
Environmental Criteria and Assessment Office, Research Triangle
Park, NC. EPA 600/8-83-014F. NTIS PB 85-115905.
The Intent 1n these assessments 1s to suggest acceptable exposure levels
whenever sufficient data were available. Values were not derived or larger
uncertainty factors were employed when the variable data were limited 1n
scope tending to generate conservative (I.e., protective) estimates. Never-
theless, the Interim values presented reflect the relative degree of hazard
associated with exposure or risk to the chemlcal(s) addressed.
Whenever possible, two categories of values have been estimated for sys-
temic toxicants (toxicants for which cancer 1s not the endpolnt of concern).
The first, the AIS or acceptable Intake subchronlc, 1s an estimate of an
exposure level that would not be expected to cause adverse effects when
exposure occurs during a limited time Interval (I.e., for an Interval that
does not constitute a significant portion of the Hfespan). This type of
exposure estimate has not been extensively used or rigorously defined, as
previous risk assessment efforts have been primarily directed towards
exposures from toxicants 1n ambient air or water where lifetime exposure 1s
assumed. Animal data used for AIS estimates generally Include exposures
with durations of 30-90 days. Subchronlc human data are rarely available.
Reported exposures are usually from chronic occupational exposure situations
or from reports of acute accidental exposure.
111
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The AIC, acceptable Intake chronic, 1s similar in concept to the ADI
(acceptable daily intake). It is an estimate of an exposure level that
would not be expected to cause adverse effects when exposure occurs for a
significant portion of the lifespan [see U.S. EPA (1980a) for a discussion
of this concept]. The AIC 1s route specific and estimates acceptable
exposure for a given route with the Implicit assumption that exposure by
other routes is insignificant.
Composite scores (CSs) for noncardnogens have also been calculated
where data permitted. These values are used for ranking reportable quanti-
ties; the methodology for their development is explained in U.S. EPA (1983).
For compounds for which there is sufficient evidence of carclnogenlclty,
AIS and AIC values are not derived. For a discussion of risk assessment
methodology for carcinogens refer to U.S. EPA (1980a). Since cancer is a
process that is not characterized by a threshold, any exposure contributes
an increment of risk. Consequently, derivation of AIS and AIC values would
be inappropriate. For carcinogens, q-|*s have been computed based on oral
and inhalation data if available.
1v
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ABSTRACT
In order to place the risk assessment evaluation 1n proper context,
refer to the preface of this document. The preface outlines limitations
applicable to all documents of this series as well as the appropriate Inter-
pretation and use of the quantitative estimates presented.
Chromium exposure has been shown to contribute to Increased Incidence of
respiratory cancers 1n occupatlonally exposed workers. The particular
form(s) of chromium responsible 1s not clear. Increases In cancer Incidence
1n experimental animals following chromium Inhalation has not been demon-
strated. However, Intrapleural and Intrabronchlal Implantation of hexava-
lent chromium compounds has resulted 1n tumors at the site of Implantation.
Hexavalent chromium has been shown to be mutagenlc 1n bacterial systems.
Using human ep1dem1olog1cal data, a unit risk of 41 (mg/kg/day)"1 has been
estimated for Inhalation exposure. Data are not available to assess the
potential cardnogenlcHy of hexavalent chromium following oral exposure.
Data are Inadequate to consider chromium as a carcinogen by the oral
route. Using data from a 1-year rat drinking water exposure study, an oral
AIC of 0.35 mg/day 1s estimated.
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ACKNOWLEDGEMENTS
The Initial draft of this report was prepared by Syracuse Research
Corporation under Contract No. 68-03-3112 for EPA's Environmental Criteria
and Assessment Office, Cincinnati, OH. Dr. Christopher DeRosa and Karen
Blackburn were the Technical Project Monitors and Helen Ball was^the Project
Officer. The final documents 1n this series were prepared for the Office of
Emergency and Remedial Response, Washington, DC.
Scientists from the following U.S. EPA offices provided review comments
for this document series:
Environmental Criteria and Assessment Office, Cincinnati, OH
Carcinogen Assessment Group
Office of A1r Quality Planning and Standards
Office of Solid Waste
Office of Toxic Substances
Office of Drinking Water
Editorial review for the document series was provided by:
Judith Olsen and Erma Durden
Environmental Criteria and Assessment Office
Cincinnati, OH
Technical support services for the document series was provided by:
Bette Zwayer, Pat Daunt, Karen Mann and Jacky Bohanon
Environmental Criteria and Assessment Office
Cincinnati, OH
vl
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TABLE OF CONTENTS
1. ENVIRONMENTAL CHEMISTRY AND FATE
2. ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS . . . .
2.1.
2.2.
ORAL
INHALATION
3. TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
3.1.
3.2.
3.3.
3.4.
SUBCHRONIC
3.1.1. Oral ,
3.1.2. Inhalation ,
CHRONIC
3.2.1. Oral
3.2.2. Inhalation ,
TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS. . . . ,
3.3.1. Oral ,
3.3.2. Inhalation
TOXICANT INTERACTIONS
4. CARCINOGENICITY
4.1.
4.2.
4.3.
4.4.
5. REGUL
HUMAN DATA
4.1.1. Oral
4.1.2. Inhalation
BIOASSAYS
4.2.1. Oral
4.2.2. Inhalation
OTHER RELEVANT DATA
WEIGHT OF EVIDENCE
ATORY STANDARDS AND CRITERIA
Page
1
4
, . . 4
4
, , 5
5
. . . 5
5
, , , 12
. . . 12
12
14
. . . 14
14
14
15
15
. . . 15
15
16
. . . 16
16
. . . 18
. . . 18
. . . 19
V11
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TABLE OF CONTENTS (cont.)
Page
6. RISK ASSESSMENT 21
6.1. ACCEPTABLE INTAKE SUBCHRONIC (AIS) 21
6.1.1. Oral 21
6.1.2. Inhalation 21
6.2. ACCEPTABLE INTAKE CHRONIC (AIC) 21
6.2.1. Oral 21
6.2.2. Inhalation 21
6.3. CARCINOGENIC POTENCY (q-|*) 21
6.3.1. Oral 21
6.3.2. Inhalation 21
7. REFERENCES 23
APPENDIX: Summary Table for Hexavalent Chromium 37
V111
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LIST OF TABLES
No. Title Page
1-1 CAS Numbers and Aqueous Solubilities of Selected Hexavalent
Chromium Compounds 2
3-1 Subchronlc Oral Toxldty of Hexavalent Chromium 1n Rats ... 6
3-2 Perforation of Nasal Septum 1n Chromate Workers 8
3-3 Nasal Lesions 1n a Chromium-Plating Plant 9
3-4 Chronic Toxldty of Hexavalent Chromium to Animals
Exposed by Inhalation 13
5-1 Standards for Occupational Exposure to Cr(VI) 20
1x
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LIST OF ABBREVIATIONS
ADI Acceptable dally Intake
AIC Acceptable Intake chronic
AIS Acceptable Intake subchronlc
BCF B1oconcentrat1on factor
CAS Chemical Abstract Service
CS Composite score
LOAEL Lowest-observed-adverse-effect level
LOEL Lowest-observed-effect level
MED Minimum effective dose
NOAEL No-observed-adverse-effect level
NOEL No-observed-effect level
ppm Parts per million
RVj Dose-rating value
RVe Effect-rating value
TWA Time-weighted average
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1. ENVIRONMENTAL CHEMISTRY AND FATE
In the hexavalent state, chromium exists as oxo species (such as Cr03>
~ and Cr02Cl2) that are strongly oxidizing (Cotton and Wilkin-
son, 1980). The CAS Registry numbers and the solubilities of a few
Important hexavalent chromium compounds are given 1n Table 1-1.
In solution, hexavalent chromium exists as hydrochromate (HCrO^),
2 2-
chromate (CrO' ) and dlchromate (Cr^O-, ) 1on1c species. The
proportion of each 1on 1n solution 1s pH dependent. In basic and neutral
pH, the chromate form predominates. As the pH 1s lowered (6.0 to 6.2), the
hydrochromate concentration Increases. At very low pH, the dlchromate
species predominate (U.S. EPA, 1984).
The primary sources of hexavalent chromium 1n the atmosphere probably
are chromate chemicals used as rust Inhibitors 1n cooling towers and emitted
as mists, partlculate matter emitted during manufacture and use of metal
chromates, and chromic add mist from the plating Industry. Hexavalent
chromium 1n air could eventually react with dust particles or other pollu-
tants to form trlvalent chromium (NAS, 1974); however, the exact nature of
such atmospheric reactions has not been studied extensively. Both hexava-
lent and trlvalent chromium are removed from air by atmospheric fallout and
precipitation (Flshbein, 1981). The atmospheric half-life for the physical
removal mechanism 1s expected to depend on the particle size and particle
density. Chromium particles of small aerodynamic diameter (<10 pm) may
remain airborne for a long period (U.S. EPA, 1984).
Hexavalent chromium may exist In aquatic media as water soluble complex
anlons and may persist 1n water for a long time. Hexavalent chromium is a
moderately strong oxidizing agent and may react with organic matter or other
-1-
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TABLE 1-1
CAS Numbers and Aqueous Solubilities of Selected
Hexavalent Chromium Compounds*
Compound CAS No. Water Solubility
Ammonium chromate 7788-98-9 40.5 g/100 ma at 30°C
(NH4)2 Cr04
Calcium chromate 13765-19-0 2.23 g/100 mil at 20°C
Potassium
K2Cr04
Potassium
K2Cr207
chromate
dichromate
Sodium chromate
Na2Cr04
Chromic acid
Cr03
7789-00-6
7789-50-9
7775-11-3
1333-82-0
62.
4.9
87.
61.
9 g/100
g/100
3 g/100
7 g/100
ma
ma
ma
ma
at
at 0
at
at
20
o
C
30
0
0
°C
°C
C
*Sources: Weast, 1980; Hartford, 1979
-2-
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reducing agents to form trlvalent chromium. The trlvalent chromium will
eventually be precipitated as Cr(L'xH_0. Therefore, 1n surface water
I- O (L
rich 1n organic content, hexavalent chromium will exhibit a much shorter
lifetime (Callahan et al., 1979).
Any hexavalent chromium 1n soil 1s expected to be reduced to trlvalent
chromium by the organic matter 1n soil. The primary processes by which the
converted trlvalent chromium 1s lost from soil are aerial transport through
aerosol formation and surface water transport through runoff (U.S. EPA,
1984). Very little chromium Is leached from soil because 1t 1s present as
Insoluble CrO,,.xH00 (Flshbeln, 1981).
t « £•
The BCF for hexavalent chromium In fish muscle appears to be <1.0 (U.S.
EPA, 1980b), but values of 125 and 192 were obtained for oyster and blue
mussel, respectively (U.S. EPA, 1980b).
-3-
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2. ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS
2.1. ORAL
Absorption of Ingested hexavalent chromium 1s estimated to be <5%.
Donaldson and Barreras (1966) fed Na2slCrO. to rats and humans. Based
on mean urinary excretion of 51Cr, absorption was estimated to be 2.1% 1n
humans. In rats, -2% of the administered dose was absorbed based on fecal
excretion of 51Cr. When Na.51CrO. was administered Intraduodenaly
(1n humans) or Intrajejunally (1n rats), however, absorption was estimated
to -50 and -25%, respectively.
MacKenzle et al. (1959) administered Na251CrO. to rats by gavage.
Based on urinary excretion, absorption was estimated to be 6% 1n fasted rats
and 3% 1n nonfasted rats.
2.2. INHALATION
A study by Langard et al. (1978) Indicates that water-soluble hexavalent
chromium 1s. absorbed rapidly by Inhalation. Rats were exposed to zinc
chromate dust at a level of 7.35 mg/m3. After 0, 100, 250 and 350 minutes
of exposure, the concentrations of chromium 1n the blood (yg/ms,) were
0.007, 0.024, 0.22 and 0.31, respectively.
In the second part of this study, rats were exposed to the same level
for 6 hours on 4 consecutive days. Blood concentrations appeared to peak at
the end of the second exposure and then began to decline slowly. Mean blood
chromium values measured at the end of each exposure period averaged 0.03,
0.56, 0.46 and 0.34 yg/ma, for exposures 1-4, respectively. No signifi-
cant differences 1n absorption as reflected by blood chromium levels were
noted between the sexes or between day and night exposures.
-4-
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3. TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
3.1. SUBCHRONIC
3.1.1. Oral. Data from two subchronlc studies Involving oral exposure to
hexavalent chromium are summarized 1n Table 3-1.
MacKenzle et al. (1958) exposed groups of rats, both male and female, to
potassium dlchromate (0-25 ppm of hexavalent chromium) 1n drinking water for
1 year. Since no effects were observed at any level of treatment, a NOEL
can be established based on body weight, gross external condition, hlsto-
pathologlcal analysis and blood chemistry. Converting 25 ppm to mg/kg/day,
25 ppm (mg/a, water) 1s multiplied by the average water consumption/day for
a rat (0.035 8,/day), and divided by the weight of an average rat (0.35 g),
to give a value of 2.50 mg/kg/day.
The study by Gross and Heller (1946), lacking detailed pathological
analysis and sufficiently large sample sizes (two animals/treatment level),
cannot be used for quantitative risk assessment.
3.1.2. Inhalation. Pertinent data regarding subchronlc exposure of
animals to hexavalent chromium by Inhalation could not be located 1n the
available literature; however, there are many studies regarding occupational
exposure of humans to hexavalent chromium.
Bloomfleld and Blum (1928) examined 23 men from 6 chromium plating
plants 1n the United States. Fourteen of these workers typically spent 2-7
hours/day over vats of chromic add, which generated airborne hexavalent
chromium ranging from 0.12-5.6 mg/m3. These men experienced nasal tissue
damage. Including perforated septum (2), ulcerated septum (3), chrome holes
(6), nosebleed (9) and Inflamed mucosa (9). In general, the 9 remaining
workers examined, not directly exposed to chromium vapors, had only Inflamed
mucosae.
-5-
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TABLE 3-1
Subchronic Oral Toxlclty of Hexavalent Chromium In Rats
Number of Animals
Dose and Compound
Period of
Exposure
Endpolnts Monitored and Effect
Reference
9 females, 12 males
at 25 ppm
10 males, 10 females
at 0 ppm
8 males, 8 females
at other treatment
levels
1 male, 1 female per
level of treatment
0, 0.45, 2.2, 4.5,
7.7, 11, 25 ppm as
potassium dlchromate
In drinking water
0, 0.036, 0.072,
0.143, 0.2854 Cr(VI)
as zinc chromate or
0, 0.033, 0.067,
0.134 or 0.268%
Cr(VI) as potassium
chromate In feed
1 year No effect based on body weight,
gross external condition, hlsto-
pathologlcal analysis and blood
chemistry.
2-3 months Animals were "subnormal" and
sterile at all doses of zinc
chromate and at 0.134 and
0.268% potassium chromate.
MacKenzle
et al., 1958
Gross and
Heller, 1946
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Several other studies report nasal tissue destruction resulting from
hexavalent chromium. The United States Health Public Service conducted a
study of workers 1n seven chromate-produdng plants 1n the early 1950s. The
results Indicated severe nasal tissue destruction but exposure levels were
not measured; hence, the data are of limited usefulness (Federal Security
Agency, 1953).
Mancuso (1951) reported on physical examinations of a random sample of
97 workers from a chromate-chemlcal plant. The results, presented in Table
3-2, Indicated that 61 of the 97 workers (63%) had septal perforation. The
data suggested to the author that Cr(III) may be partly responsible for the
perforations; however, later studies have not provided support for this
theory.
The results of examinations of nine workers In a chrome-plating plant
are shown 1n Table 3-3. Analyses of air samples showed chromium concentra-
tions of 0.18-1.4 mg/m3. Some degree of nasal septal ulceratlon was seen
1n 7 of the 9 men, with 4 of 7 demonstrating frank perforations (Kleinfeld
and Russo, 1965). The effects of chromium exposure for a specific length of
time at a fixed concentration were not studied.
Vigllani and Zurlo (1955) reported nasal septal perforation 1n workers
exposed to chromic acid and chromates In concentrations of 0.11-0.15
mg/m3. The lengths of exposure were not known. Otolaryngologic examina-
tions of 77 persons exposed to chromic add aerosol during chrome plating
revealed 19% to have septal perforation and 48% to have nasal mucosal
irritation. These people averaged 6.6 years of exposure to an air chromium
concentration of 0.4 mg/m3. In 14 persons, paplllomas of the oral cavity
and larynx were found. The diagnosis of papilloma was confirmed by hlsto-
loglc examination. There were no signs of atypical growth or malignant
degeneration (Hanslian et al., 1967).
-7-
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TABLE 3-2
Perforation of Nasal Septum 1n Chromate Workers*
Ratio of
Insol Cr+3 Chromium concentration, No. Workers
to sol Cr+6 yg/fn3 (as Cr) Examined
Workers 1n plant
<1.0:1
1.1 to 4.9:1
>5.0:1
TOTAL
Office workers
<0.25
0.26 - 0.51
<0.52
<0.25
0.26 - 0.51
>0.52
<0.25
0.26 - 0.51
>0.52
0.06
4
7
8
9
32
15
7
2
13
97
4
Workers with
Septal Perforation
No.
2
3
4
7
20
11
2
1
11
61
0
%
50
43
50
78
63
73
29
50
85
63
0
*Source: Mancuso, 1951
Insol = Insoluble; sol = soluble
-8-
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TABLE 3-3
Nasal Lesions In a Chromium-Plating Plant*
Case Age
(yrs)
1 30
2 19
3 19
4 18
5 47
6 45
7 23
8 20
9 48
Duration of
Exposure
(mos)
6
2
12
9
10
6
1
0.5
9
Findings
perforated septum
perforated septum
perforated septum
perforated septum
ulcerated septum
ulcerated septum
ulcerated septum
moderate Injection of
septum and turblnates
moderate Injection of
septum
*Source: Klelnfeld and Russo, 1965
-9-
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The literature suggests that chromium compounds are also responsible for
a wide variety of other respiratory effects. German studies demonstrating
mixed results from exposure to chromium compounds were reviewed by the U.S.
EPA (1984). Because In all of these studies no correlation between symptom-
atology, physical signs, length of exposure and dose of chromium compounds
was available, they are not useful for risk assessment and are not reviewed
here.
In the United States, 897 workers In chromate-produclng plants had a
higher Incidence of severely red throats and pneumonia, but did not show any
Increase 1n the Incidence of other respiratory diseases when compared with
control groups. Although bilateral hllar enlargement was observed, there
was no evidence of excessive pulmonary flbrosls 1n these workers (Federal
Security Agency, 1953). The various lung changes described 1n these workers
may represent a nonspecific reaction to Irritating material or a specific
reaction to chromium compunds. Many of the conditions mentioned occur
widely In the general population (NAS, 1974).
Gomes (1972) examined 303 employees who worked 1n 81 electroplating
operations 1n Sao Paulo, Brazil. Over two-thirds of the workers had mucous
membrane or cutaneous lesions, with many of them having ulcerated or
perforated nasal septa. The duration of exposure was not stated, but the
author mentioned that the harmful effects were noted 1n <1 year. A direct
correlation between workers exposed to a given airborne concentration of
chromium (VI) and the development of harmful effects could not be made.
Cohen and Kramkowskl (1973) and Cohen et al. (1974) examined 37 workers
employed by a chromium-plating plant. Within 1 year of employment, 12
workers experienced nasal ulceratlon or perforation. The airborne chromium
(VI) concentrations ranged from <0.71-9.12
-10-
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In a chromium plating plant where the maximum airborne chromium (VI)
concentration was 3 yg/m3, no ulcerated nasal mucosa or perforated nasal
septa were found; however, half of the 32 employees had varying degrees of
mucosal Irritation (Markel and Lucas, 1973). The authors did not consider
this to be significant, because the survey was carried out at the peak of
the 1972-1973 Influenza epidemic.
Machle and Gregorlus (1948) reported an Incidence of nasal septa!
perforation of 43.5% In 354 employees who worked 1n a chromate-produdng
plant that manufactured sodium chromate and bichromate. At the time of the
study, airborne chromate concentrations ranged from 10 to 2800 yg/m3.
The plant had been 1n operation for at least 17 years, and some employees
probably worked 1n the plant when reverberatory furnaces, a prominent source
of high chromate exposure, were used.
In a more recent study, lung function, the condition of the nasal septum
and subjective symptoms related to respiratory health (data obtained by
questionnaire) were compared In unexposed controls (119) and workers (43)
exposed to chromic add 1n chrome plating operations (Undberg and
Hedenstlerna, 1983). Workers were further divided Into low (<2) and high
(>2 yg Cr* /m3) exposure groups. Complaints of diffuse nasal symptoms
("constantly running nose," "stuffy nose" or "a lot to blow out") were
registered by 4/19 workers 1n the low group and half of the 24 workers 1n
the high group. Complaints were not registered by workers exposed to <1
yg/m3. The frequency of throat and chest symptoms did not appear to be
related to treatment.
Examination of the nasal septum revealed that damage was significantly
greater 1n exposed workers than 1n unexposed controls and appeared to be
somewhat more severe 1n the high group than the low group. Measurements of
-11-
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lung function revealed a detrimental effect due to exposure to chromic add
fumes, but significant differences between low and high groups were not
observed. There was a tendency for lung function parameters to return to
normal over a 2-day weekend.
Various other disease states have been attributed to chromium, but, In
most cases, the etlologlc relation to chromium 1s doubtful because of the
presence of other chemicals (NAS, 1974). These studies, reviewed by the
U.S. EPA (1984), will not be reviewed here.
3.2. CHRONIC
3.2.1. Oral. Only one chronic study pertaining to the oral toxldty of
hexavalent chromium was located 1n the available literature. Anwar et al.
(1961) exposed dogs orally to potassium chromate 1n drinking water for 4
years. Treatment levels were 0, 0.45, 2.25, 4.5, 6.75 and 11.2 ppm potas-
sium chromate; there were two dogs/group. No effects were observed with
regard to gross and microscopic analysis of all major organs, urlnalysls,
and weights of spleen, liver and kidney. The exposure of 11.2 ppm can be
converted to units of mg/kg/day by multiplying 11.2 ppm by the average dally
water consumption for a dog of average weight (0.0275 i/kg/day) to produce
a NOEL of 0.31 mg potassium chromate/kg/day. This 1s equivalent to 0.089 mg
Cr(VI)/kg/day.
3.2.2. Inhalation. Data regarding the chronic toxldty of hexavalent
chromium administered by Inhalation are summarized 1n Table 3-4.
Netteshelm et al. (1971) exposed mice to an aerosol of calcium chromate
at levels of either 10 mg/m3 (4.33 mg Cr(VI)/m3) or 30 mg/m3 (10 mg
Cr(VI)/m3) for 5 hours/day, 5 days/week for life. Based on epithelial
necrosis, marked hyperplasla and atrophy of the pulmonary bronchi,
emphysema-like changes, and atrophy of the spleen and liver, a LOAEL can be
-12-
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TABLE 3-4
Chronic Toxlclty of Hexavalent Chromium to Animals Exposed by Inhalation
Species
Nice
Number of Animals
136 total (male
and female);
unspecified number
of controls
Dose and Compound
13 or 30 mg calcium
chromate aerosol/m3
[4.33 or 10 mg Cr(Vl)/m»,
respectively]
Period of
Exposure
5 hours/day,
5 days/week
for life
Endpolnts Monitored and Effect
At 6-month Intervals, bacteriological.
parasltologlcal, vlrologlcal and htsto-
pathologlcal analyses were performed.
Reference
Netteshelm et
al.. 1971
oo
I
Rats
100
2 mg calcium chromate S89/B91 days
aerosol/m» [0.67 Cr(Vl)/m»]
Hamsters 100
10 mg/m» level:
4.33 mg/m' level:
early death, rapid
weight loss, fatty
liver, distended and
atrophlc Intestines
epithelial necro-
sis, marked hyper-
plasla and atrophy
of pulmonary
bronchi, alveolar
scarring after 6
months; after 2
years, atrophy of
spleen and liver
Laryngeal hyperplasla (2) and laryn-
geal metaplasia (3) were found upon
examination Immediately after treat-
ment was stopped.
Squamous metaplasia (8) and laryngeal
hyperplastas (8) were found Immedi-
ately after treatment was stopped.
No other details were provided.
Laskln. 1972
-------
established at 4.33 mg Cr(VI)/m3. Adjusting to units of mg/kg/day, 4.33
mg/m3 is multiplied by the product of 5 hours/24 hour day times 5 days of
exposure/week times the average Inhalation rate/day for a mouse (0.05
mVday). This value 1s subsequently divided by the average body weight of
a mouse (0.03 kg) to yield a value of 1.07 mg CR(VI)/kg/day.
Laskin (1972) exposed rats and hamsters to calcium chromate aerosol at a
level of 2 mg/m3 (0.67 mg Cr(VI)/m3) for 589 of 891 days. Although some
laryngeal hyperplaslas and metaplasias were observed 1n both species tested,
details pertaining to controls were not given 1n the available review.
3.3. TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS
3.3.1. Oral. Pertinent data regarding the teratogenidty of orally
administered hexavalent chromium could not be located in the available
literature.
3.3.2. Inhalation. Pertinent data regarding the teratogenicity of
inhaled hexavalent chromium could not be located in the available literature.
3.4'. TOXICANT INTERACTIONS
Pertinent data regarding the toxicant Interactions of hexavalent chro-
mium with other compounds could not be located in the available literature.
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4. CARCINOGENICITY
4.1. HUMAN DATA
4.1.1. Oral. Pertinent human data regarding' the cardnogenlcHy of
Ingested hexavalent chromium could not be located 1n the available litera-
ture.
4.1.2. Inhalation. Occupational exposure to chromium compounds via
Inhalation has been studied 1n the chromate, chrome-plating and chrome
pigment Industries.
Workers In the chromate Industry are exposed to both tMvalent and hexa-
valent compounds of chromium. Ep1dem1olog1cal studies of chromate produc-
tion plants 1n Japan, Great Britain, West Germany and the United States have
revealed a correlation between occupational exposure to chromium and lung
cancer, but the specific etlologlcal agent was not Identified (Machle and
GregoMus, 1948; Brlnton et al., 1952; Baetjer, 1950a,b; Mancuso and Hueper,
1951; Mancuso, 1975; Taylor, 1966; Enterllne, 1974; Hayes et al., 1979; H111
and Ferguson, 1979; Bldstrup, 1951; Bldstrup and Case, 1956; Alderson et
al., 1981; Todd, 1962; Watanabe and Fukuchi, 1975; Ohsakl et al., 1978; Sano
and MHohara, 1978; Satoh et al., 1981; Korallus et al., 1982). Of these,
the studies by Mancuso and Hueper (1951) and Mancuso (1975) are of Interest,
since they were used by the Carcinogen Assessment Group to derive a cancer-
based criterion for lifetime exposure to chromium (U.S. EPA, 1984).
Mancuso and Hueper (1951) analysed the vital statistics of a cohort of
chromate workers (employed for >1 year from 1931-1949 1n a Pa1nesv1lle, OH
chromate plant) In order to Investigate lung cancer associated with chromate
production. Of the 2931 deaths of males 1n the county where the plant was
located, 34 (1.2%) were due to respiratory cancer. Of the 33 deaths among
the chromate workers, however, 6 (18.2%) were due to respiratory cancer.
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The difference between these groups 1s significant at p<0.01. Furthermore,
two of these workers exposed primarily to Insoluble chromlte had -390 and
250 yg chromium/10 g of lung tissue, respectively. By contrast, chromium
levels 1n the lungs of nonexposed Individuals were nearly zero.
In an update of the Mancuso and Hueper (1951) study, Mancuso (1975)
followed 332 of the workers employed from 1931-1951 until 1974. By 1974,
>50% of this cohort had died. Of these men, 63.6, 62.5 and 58.3% of the
cancer deaths for men employed from 1931-1932, 1933-1934 and 1935-1937,
respectively, were due to lung cancer. Mancuso (1975) reported that these
lung cancer deaths were related to Insoluble (tMvalent), soluble (hexava-
lent) and total chromium exposure, but the small numbers involved make this
relationship questionable (U.S. EPA, 1984).
In two studies derived from the chrome pigment industry, workers were
exposed only to hexavalent chromium. In both studies, exposure to chromium
was correlated with lung cancer (Langard and Norseth, 1975; Davies, 1978,
1979).
Studies from the chrome-plating industry either demonstrated a correla-
tion between lung cancer and exposure to chromium compounds (Royle, 1975),
or were inconclusive (Silversteln et al., 1981; Okubo and Tsuchlya, 1979).
4.2. BIOASSAYS
4.2.1. Oral. Pertinent data regarding the carclnogenlcity of orally
administered hexavalent chromium in animal systems could not be located in
the available literature.
4.2.2. Inhalation. To date, It has not been possible to Induce tumors in
laboratory animals by exposing them to chromium (either tMvalent or hexa-
valent) via inhalation.
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Baltjer et al. (1959) chronically exposed three strains of mice (Strain
A, Swiss, C57B1) and mixed-breed rats to ~1 mg chromium dust/m3, and
reported no Increase In the Incidence of lung tumors with respect to
untreated controls. Similar results were obtained by Steffee and Baetjer
(1965) for Wlstar rats, rabbits and guinea pigs exposed to chromium dust.
Netteshelm et al. (1971) exposed C57B1 mice to 4.33 mg calcium chromate
dust/m3, 5 hours/day, 5 days/week for life, and reported an Increase 1n
the number of lung tumors with respect to controls. Since statistical
analysis was not performed, however, the significance of these results 1s
unclear. In a review of this study, IARC (1980) concluded that a signifi-
cant excess of treatment-related tumors was not observed.
There 1s some evidence that hexavalent chromium may be carcinogenic
following Intrapleural Implantation of calcium chromate (Hueper and Payne,
1962) or 1ntrabronch1al Implantation of strontium chromate, calcium chromate
or zinc chromate (Levy and Martin, 1983). These tumors, however, were
observed at the site of Implantation. In addition, Stelnhoff et al. (1983)
have shown that Intratracheal administration to rats both Na?Cr?07 and
CaCrO. produced Increased Incidences of lung tumors following 30 months of
administration.
In contrast, zinc chromate was not carcinogenic following Intratracheal
Implantation (Steffee and Baetjer, 1965; Baetjer et al., 1959), nor were
barium chromate, chromium dust, lead chromate, chromlte ore, powdered chro-
mium metal, potassium chromate and sodium dlchromate following 1ntra-
bronchlal, Intrapleural or Intratracheal Implantation (Steffee and Baetjer,
1965; Baetjer et al.. 1959; Hueper, 1955, 1958; Payne, 1960; Hueper and
Payne, 1962; Levy and Venltt, 1975).
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4.3. OTHER RELEVANT DATA
Hexavalent chromium has been shown to be mutagenlc 1n bacterial systems
1n the absence of a mammalian activating system (VenHt and Levy, 1974;
N1sh1oka, 1975; Nakamuro et a!., 1978; Green et al., 1976; Kanematsu et al.,
1980; Lofroth and Ames, 1978; Newbold et al., 1979; Bonattl et al., 1976;
Fukanaga et al., 1982), and not mutagenlc when a mammalian activating system
1s present (Lofroth, 1978; PetrllH and Deflora, 1977, 1978a,b). Hexavalent
chromium 1s also mutagenlc 1n eucaryotlc test systems (Bonattl et al., 1976;
Newbold et al., 1979; Fukanaga et al., 1982) and clastogenlc In cultured
mammalian cells (Raffetto, 1977; Levls and Majone, 1979; Umeda and N1shi-
mura, 1979; Tsuda and Kato, 1977; Newbold et al., 1979; Nakamuro et al.,
1978; Stella et al., 1982; Ohno et al., 1982; Gomez-Arroyo et al., 1981;
Wild, 1978; Sarto et al., 1982).
4.4. WEIGHT OF EVIDENCE
IARC (1980) has concluded that there 1s sufficient evidence of respira-
tory cardnogenlcHy 1n men occupatlonally exposed during chromate produc-
tion; however, the ep1dem1olog1cal data do not allow elucidation of the
relative contributions to carcinogenic risk of metallic chromium, tMvalent
chromium, hexavalent chromium, or of soluble versus Insoluble chromium
compounds. Furthermore, the animal studies using non-natural routes of
administration have provided sufficient evidence that certain compounds of
hexavalent chromium (sintered calcium chromate, lead chromate, strontium
chromate, sintered chromium trioxlde and zinc chromate) are carcinogenic.
Therefore, IARC (1982) classified chromium and chromium compounds as Group I
chemicals. Applying the criteria proposed by the Carcinogen Assessment
Group of the U.S. EPA for evaluating the overall weight of evidence for
cardnogenlcHy to humans (Federal Register, 1984), hexavalent chromium 1s
most appropriately designated a Group A - Human Carcinogen.
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5. REGULATORY STANDARDS AND CRITERIA
Recommended standards for occupational exposure to hexavalent chromium
compounds are summarized 1n Table 5-1.
The U.S. EPA (19805) has recommended a criterion of 0.05 mg/8. for the
concentration of hexavalent chromium 1n water. They also established an
Interim ADI of 0.175 mg/man/day for chronic 1ngest1on of hexavalent chromium
based on the study of MacKenzle et al. (1958). These levels are not
Intended to protect against potential carcinogenic effects of chromium VI
compounds. The considered opinion when these levels were suggested was that
Cr(VI) would potentially be reduced In the gastrointestinal tract to
Cr(III). Although this 1s a plausible assumption, conclusive data are not
available.
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TABLE 5-1
Standards for Occupational Exposure to Cr(VI)
Compound
Standard
(mg/m3)
Reference
Noncardnogenlc chromium VI*
Carcinogenic chromium
Soluble chromic or chromous salt
Insoluble salts
Water soluble compounds of
chromium (VI) (noncarclnogenlc)
Insoluble compounds of chromium
(VI) (carcinogenic potential)
0.025 TWA
0.050 ceiling
0.001 TWA
0.500 TWA
1.000 TWA
0.05 TWA
0.05 TWA
NIOSH, 1975
NIOSH, 1975
OSHA, 1978
OSHA, 1978
ACGIH, 1983
ACHIH, 1983
*Monochromates and dichromates of hydrogen, lithium, potassium, rubidium,
cesium, ammonium and chromic oxide
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6. RISK ASSESSMENT
6.1. ACCEPTABLE INTAKE SUBCHRONIC (AIS)
6.1.1. Oral. A 1-year oral study has established a NOEL for hexavalent
chromium in rats of 2.5 mg/kg/day (MacKenzle et al., 1958) (see Section
3.1.1.). Applying an uncertainty factor of 100 (10 for Interspedes
extrapolation and 10 for 1nter1nd1v1dual variability) and assuming a 70 kg
body weight results 1n an estimated oral AIS of 1.75 mg/day.
6.1.2. Inhalation. Hexavalent chromium has been shown to be a human
carcinogen by the Inhalation route for which data are sufficient for
computation of a q,*. It 1s Inappropriate, therefore, to calculate an
Inhalation AIS for hexavalent chromium.
6.2. ACCEPTABLE INTAKE CHRONIC (AIC)
6.2.1. Oral. Using the oral AIS of 1.75 mg/day and applying an addi-
tional uncertainty factor of 5 to adjust for a study which 1s of Inter-
mediate duration between subchronlc and chronic results in an .estimated oral
AIC of 0.35 mg/day. This 1s the approach recommended by U.S. EPA (1985).
6.2.2. Inhalation. Hexavalent chromium has been shown to be a human
carcinogen for which data are sufficient for computation of a q *. It is
inappropriate, therefore, to calculate an Inhalation AIC for hexavalent
chromium.
6.3. CARCINOGENIC POTENCY (q^)
6.3.1. Oral. The lack of data regarding the carcinogeniclty of orally
administered hexavalent chromium precludes assessment of carcinogenic risk.
6.3.2. Inhalation. Based on the epidem1olog1cal study of Mancuso (1975),
the Carcinogen Assessment Group has derived a cancer-based criterion for
exposure to chromium by Inhalation (U.S. EPA, 1984). Assuming a lifetime
-21-
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exposure to 1 yg elemental chrom1um/m3, the upper limit unit carcino-
genic risk was estimated to be 1.16xlO~2 (yg/m3)"1 1n units of
lifetime risk per 1 yg/m3 exposure for humans. This unit risk may be
transformed to units of (mg/kg/day}"1 as follows: the concentration of
1 yg/m3 Is equivalent to 20 yg/day or 0.02 mg/day assuming a human
respiratory rate of 20 mVday. Assuming an average human weighs 70 kg,
the dosage becomes 2.857xlO~4 mg/kg/day. The unit risk of 1.16xlO"2
(yg/m3)"1 * 2.857xlO~4 mg/kg/day results 1n an expression of unit
risk of 41 (mg/kg/day)'1.
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7. REFERENCES
ACGIH (American Conference of Governmental Industrial Hyglenists). 1983.
Threshold Limit Values for Chemical Substances and Physical Agents 1n the
Workroom Environment with Intended Changes for 1983-1984. Cincinnati, OH.
p. 15.
Alderson, M.R., N.S. Rattan and L. Bldstrup. 1981. Health of workmen 1n
the chromate-platlng Industry In Britain. Br. J. Ind. Med. 38: 117-124.
(Cited 1n U.S. EPA, 1984)
Anwar, R.A., C.F. Langham, C.A. Hoppert, B.V. Alfredson and R.U. Byerrum.
1961. Chronic toxlclty studies. III. Chronic toxldty of cadmium and
chromium 1n dogs. Arch. Environ. 3: 456. (Cited 1n U.S. EPA, 1984)
Baetjer, A.M. 1950a. Pulmonary carcinoma 1n chromate workers. I. A review
of the literature and report of cases. Arch. Ind. Hyg. Occup. Med. 2:
487-504. (Cited 1n U.S. EPA, 1984)
Baetjer, A.M. 1950b. Pulmonary carcinoma In chromate workers. II. Inci-
dence on basis of hospital records. Arch. Ind. Hyg. Occup. Med. 2:
505-516. (Cited 1n U.S. EPA, 1984)
Baetjer, A.M., J.F. Lowney, H. Steffee and V. Budacz. 1959. Effect of
chromium on Incidence of lung tumors In mice and rats. Arch. Ind. Health.
20: 124-135. (Cited in IARC, 1980; U.S. EPA, 1984)
-23-
-------
Bldstrup, P.L. 1951. Carcinoma of the lung In chromate workers. Br. J.
Med. 8: 302-305. (Cited In U.S. EPA, 1984)
Bldstrup, P.L. and R.A.M. Case. 1956. Carcinoma of the lung 1n workmen 1n
the bichromates-producing Industry 1n Great Britain. Br. J. Ind. Med. 13:
260-264. (Cited In U.S. EPA, 1984)
Bloomfleld, O.J. and W. Blum. 1928. Health hazards 1n chromium plating.
Public Health Rep. 43: 2330-2351. (Cited 1n U.S. EPA, 1984)
Bonatti, S., M. Melnl and A. Abbondandolo. 1976. Genetic effects of potas-
sium dlchromate 1n Schlzosaccharomyces pombe. Mutat. Res. 38: 147-150.
(Cited 1n U.S. EPA, 1984)
BMnton, H..P., E.S. Rasler and A.L. Koven. 1952. Morbidity and mortality
experience among chromate workers. Public Health Rep. 67: 835-847. (CHed
In U.S. EPA, 1984)
Callahan, M.A., M.W. Sllmak and N.W. Bagel, et al. 1979. Water-Related
Environmental Fate of 129 Priority Pollutants, Vol. II. U.S. EPA, Office of
Water Planning and Standards, Office of Water and Waste Management, Washing-
ton, DC. EPA 440/4-79-029.
Cohen, S.R. and R.S. Kramkowsl. 1973. Health Hazard Evaluation Determina-
tion, Report No. 72-118-104. Cincinnati, OH, U.S. DHEW, NIOSH. (CHed In
U.S. EPA, 1984)
-24-
-------
Cohen, S.R., O.M. Davis and R.S. Kramkowsk!. 1974. Clinical manifestations
of chromic add toxlclty -- Nasal lesions 1n electroplate workers. Cutls.
13: 558-568. (Cited 1n U.S. EPA, 1984)
Cotton, F.A. and G. Wilkinson. 1980. Advanced Organic Chemistry. A
Comprehensive Test, 4th ed. John Wiley and Sons, NY. p. 719-736.
Davles, J.M. 1978. Lung-cancer mortality of workers making chrome pig-
ments. Lancet. 1: 384. (Cited 1n U.S. EPA, 1984}
Davles, J.M. 1979. Lung cancer mortality In workers 1n chromate pigment
manufacture: An ep1dem1olog1cal survey. J. 011 Chem. Assoc. 62: 157-163.
(Cited 1n U.S. EPA, 1984)
Donaldson, R.M. and R.F. Barreras. 1966. Intestinal absorption of trace
quantities of chromium. J. Lab CUn. Med. 68: 484-493. (Cited 1n U.S.
EPA, 1984)
Enterllne, P.E. 1974. Respiratory cancer among chromate workers. J.
Occup. Med. 16: 523-526. (Cited 1n U.S. EPA, 1984)
Federal Register. 1984. Environmental Protection Agency. Proposed guide-
lines for carcinogenic risk assessment. Federal Register. 49: 46294-46299.
Federal Security Agency. 1953. Health of Workers 1n Chromate Producing
Industry. A Study. U.S. Public Health Service Publication No. 192.
Washington, DC. U.S. Government Printing Office. 131 p. (Cited 1n U.S.
EPA, 1984)
-25-
-------
F1shbe1n, L. 1981. Source, transport and alterations of metal compounds:
An Overview. I. Arsenic, beryllium, cadmium, chromium and nickel. Environ.
Health Perspect. 40: 43-64.
Fukanaga, M., Y. Kurachl and Y. M1zuguch1. 1982. Action of some metal Ions
on yeast chromosomes. Chem. Pharm. Bull. 30: 3017-3019. (Cited 1n U.S.
EPA, 1984)
Gomes, E.R. 1972. Incidence of chromium-Induced lesions among electroplat-
ing workers 1n Brazil. Ind. Med. 41: 21-25. (Cited In U.S. EPA, 1984)
Gomez-Arroyo, S., M. Altamlrano and R. V1llalobos-P1etr1n1. 1981. Slster-
chromatld exchanges Induced by some chromium compounds 1n human lymphocytes
1n vitro. Mutat. Res. 90: 425-431. (Cited In U.S. EPA, 1984)
Green, M.H.L., W.J. Muriel and B.A. Bridges. 1976. Use of a simplified
fluctuation test to detect low levels of mutagens. Mutat. Res. 38: 33-42.
(Cited 1n U.S. EPA, 1984)
Gross, W.G. and U.G. Heller. 1946. Chromium 1n animal nutrition. J. Ind.
Hyg. Toxlcol. 28: 52. (Cited 1n U.S. EPA, 1984)
Hansllan, L., J. Nauratll, J. Jurak and M. Kotrle. 1967. Upper respiratory
tract lesions from chromic add aerosols. Pracovnl. Lekar. 19:294-298.
(Czech., English Abstr.) (Cited 1n U.S. EPA, 1984).
-26-
-------
.Hartford, W.H. 1979. Chromium Compounds. .In.: K1rk-0thmer Encyclopedia of
Chemical Technology, 3rd ed., Vol. 6, M. Grayson and D. Eckroth, Ed. John
Wiley and Sons, Inc., NY. p. 82-120.
Hayes, R.B., A.M. L1l1enf1eld and L.M. Snell. 1979. Mortality 1n chromium
chemical production workers: A prospective study. Internat. J. Ep1dem1ol.
8: 365-374.
H111, W.J. and W.S. Ferguson. 1979. Statistical analysis of ep1dem1olog1-
cal data from chromium chemical manufacturing plant. J. Occup. Med. 21:
103-106. (Cited 1n U.S. EPA, 1984)
Hueper, W.C. 1955. Experimental studies 1n metal cardnogenesls. VII.
Tissue reactions to parenterally Introduced powdered metallic chromium and
chromlte ore. J. Natl. Cancer Inst. 16(2): 447-469. (Cited 1n U.S. EPA,
1984)
Hueper, W.C. 1958. Experimental studies 1n metal cancerogenesls. X.
Cancerogenlc effects of chromlte ore roast deposited 1n muscle tissue and
pleural cavity of rats. Am. Med. Assoc. Arch. Ind. Health. 18: 284-291.
(Cited 1n U.S. EPA, 1984)
Hueper, W.C. and W.W. Payne. 1962. Experimental studies 1n metal cardno-
genesls — Chromium, nickel Iron arsenic. Arch. Environ. Health. 5:
445-462. (Cited In IARC, 1980; U.S. EPA, 1984)
-27-
-------
IARC (International Agency for Research on Cancer). 1980. Chromium and
Chromium Compounds. In: Some Metals and Metallic Compounds. IARC Mono-
graphs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans.
IARC, WHO, Lyon, France. 23: 205-323.
IARC (International Agency for Research on Cancer). 1982. Results and
Conclusions. Ln: Chemicals, Industrial Processes and Industries Associated
with Cancer 1n Humans. IARC Monographs on the Evaluation of the Carcino-
genic Risk of Chemicals to Humans. IARC, WHO, Lyon, France. 1-29 (Suppl.
4): 18.
Kanematsu, N., M. Hara and T. Kada. 1980. Rec assay and mutagenldty
studies on metal compounds. Mutat. Res. 77: 109-116. (Cited 1n U.S. EPA,
1984)
Klelnfeld, M. and A. Russo. 1965^ Ulceratlons of the nasal septum due to
Inhalation of chromic acid mist. Ind. Med. Surg. 34: 242-243. (Cited In
U.S. EPA, 1984)
Korallus, V., H. Lange, A. Ness, E. Wuestefeld and T. Zwlngers. 1982.
Relationships between precautionary measures and bronchial carcinoma mortal-
ity 1n the chromate-produdng Industry. Arbe1tsmed1z1n, Soda! Medlzln
Prevent1vmed1z1n. 17(7): 159-167. (Cited 1n U.S. EPA, 1984)
Langard, S. and T. Norseth. 1975. A cohort study of bronchial carcinomas
1n workers producing chromate pigments. Br. J. Ind. Med. 32: 62-65.
(Cited 1n U.S. EPA, 1984)
-28-
-------
Langard, S., NJ. Gundersen, D.L. Tsalev and B. Glyseth. 1978. Whole blood
chromium level and chromium execretlon 1n the rat after zinc chromate
Inhalation. Acta. Pharmacol. Toxlcol. 42:142-149. {Cited In U.S. EPA,
1984)
Laskln, S. 1972. Research 1n Environmental Sciences, Washington, DC.,
Institute of Environmental Medicine, p. 92-97. (Cited In IARC, 1980)
Levls, A.G. and F. Majone. 1979. Cytotoxlc and clastogenlc effects of
soluble chromium compounds on mammalian cell cultures. Br. J. Cancer. 40:
523-533. (Cited In U.S. EPA, 1984)
Levy, L.S. and P.A. Martin. 1983. The effects of a range of chromium-
containing materials on rat lung. Dye Color Manufacturers Assoc.
Levy, L.S. and S. VenHt. 1975. Carcinogenic and mutagenlc activity of
chromium containing materials. Br. J. Cancer. 32: 254-255. (CHed 1n
IARC, 1980)
Llndberg, E. and G. Hedenstlerna. 1983. Chrome plating: Symptoms, finding
1n the upper airways, and effects on lung functions. Arch. Environ. Health.
38(6): 367-374.
Lofroth, G. 1978. The mutagenldty of hexavalent chromium Is decreased by
mlcrosomal metabolism. Naturwlssenschaften. 65: 207-208. (CHed In U.S.
EPA, 1984)
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-------
Lofroth, G. and B.N. Ames. 1978. Mutagenlcity of Inorganic compounds 1n
Salmonella typhlmurlum: Arsenic, chromium and selenium. Am. Environ. Mut.
Soc. 8th Meeting, February 13-17, 1977, Colorado Springs. Mutat. Res. 53:
65-66. (Cited In U.S. EPA, 1984)
Machle, W. and F. GregoMus. 1948. Cancer of the respiratory system 1n the
United States chromate-produdng Industry. Public Health Rep. 63(35):
1114-1127. (Cited In U.S. EPA, 1984)
MacKenzle, R.D., R.U. Byerrum, C.F. Decker, C.A. Hoppert and F.L. Langham.
1958. Chronic toxldty studies. II. Hexavalent and trlvalent chromium
administered 1n drinking water to rats. Am. Med. Assoc. Arch. Ind. Health.
18: 232-234. (Cited In U.S. EPA, 1984)
MacKenzle, R.D., R.A. Anwar, R.U. .Byerrum and C.A. Hoppert. 1959. Absorp-
tion and distribution of 51Cr 1n the albino rat. Arch. Blochem. Blophys.
79: 200-250. (Cited 1n U.S. EPA, 1984)
Mancuso, T.F. 1951. Occupational cancer and other health hazards 1n a
chromate plant: A mdelcal appraisal. I. Lung cancer 1n chromate workers.
Ind. Med. S1ng. 20: 358-363. (Cited 1n U.S. EPA, 1984)
Mancuso, T.F. 1975. International Conference on Heavy Metals 1n the
Environment, loronto, Canada, Oct. 27-31. (Cited 1n Towlll et al., 1978;
U.S. EPA, 1984)
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-------
Mancuso, T.F. and W.C. Hueper. 1951. Occupational cancer and other health
hazards 1n a chromate plant: A medical appraisal. I. Lung cancer 1n chro-
mate workers. Ind. Med. Surg. 20: 358-363. (Cited in NIOSH, 1975; U.S.
EPA, 1984}
Markel, H.L., Jr. and J.B. Lucas. 1973. Health Hazard Evaluation Report
72-106. Cincinnati, OH, U.S. OHEW, NIOSH, Division of Technical Services,
Hazard Evaluation Services Branch. (Cited 1n NIOSH, 1975; U.S. EPA, 1984)
Nakamuro, K., K. Yoshlkawa, Y. Sayato and H. Kurata. 1978. Comparative
studies of chromosomal aberration and mutagenldty of trlvalent and hexava-
lent chromium. Mutat. Res. 58: 175-181. (Cited In U.S. EPA, 1984)
NAS (National Academy of Sciences). 1974. Medical and Biological Effects
of Environmental Pollutants: Chromium. National Academy Press, Washington.,
DC. (Cited 1n U.S. EPA, 1984)
Netteshelm, P., M.G. Hanna, Jr., D.6. Doherty, R.F. Newell and A. Hellman.
1971. Effect of calcium chromate dust, Influenza vlrum, and 100 R whole-
body X-rad1at1on on lung tumor Incidence 1n mice. J. Natl. Cancer Inst.
47: 1129-1144. (Cited 1n IARC, 1980; U.S. EPA, 1984)
Newbold, R.F., J. Amos and J.R. Connell. 1979. The cytotoxlc, mutagenlc
and clastogenlc effects of chromium-containing compounds on mammalian cells
1n culture. Mutat. Res. 67: 55-63. (Cited 1n U.S. EPA, 1984)
N1sh1oka, H. 1975. Mutagenlc activities of metal compounds 1n bacteria.
Mutat. Res. 31: 185-189. (Cited 1n U.S. EPA, 1984)
-31-
-------
NIOSH (National Institute for Occupational Safety and Health). 1975. Cri-
teria for a Recommended Standard...Occupational Exposure to Chromium (VI).
U.S. DHEW, PHS, CDC, Rockvllle, MD.
Ohno, H., F. Hanaoka and M. Yanada. 1982. IndudbllHy of slster-chromatid
exchanges by heavy-metal Ions. Mutat. Res. 104: 141-145. (Cited 1n U.S.
EPA, 1984)
Ohsakl, Y., S. Abe, K. Klmura, Y. Tsunlta, H. M1kam1 and M. Murao. 1978.
Lung cancer In Japanese chromate workers. Thorax. 33: 372-374. (CHed 1n
U.S. EPA, 1984)
Okubo, T. and K. Tsuchlya. 1979. Ep1dem1olog1cal study of chromium plater
1n Japan. B1ol. Trace Element Res. 1: 35-44. (Cited 1n U.S. EPA, 1984)
OSHA (Occupational Safety and Health Administration). 1978. A1r contaml-
nents. 29 CFR. 1910.1000. p. 99-100. (CHed In U.S. EPA, 1984)
Payne, W.W. 1960. Production of trace elements 1n whole blood by photon-
Induced x-ray fluorescence. Eur. J. Nucl. Med. 2: 277-279. (Cited In
IARC, 1980)
PetrllH, F.L. and S. DeFlora. 1977. Toxlclty and mutagenlclty of hexava-
lent chromium on Salmonella typhlmurlum. Appl. Environ. M1crob1ol. 33:
805-809. (CHed In U.S. EPA, 1984)
-32-
-------
PetrlTM, F. and S. DeFlora. 1978a. Oxidation of Inactive, tMvalent
chromium to the mutagenlc hexavalent form. Mutat. Res. 58: 167-178.
(Cited In U.S. EPA, 1984)
PetrHH, F.L. and S. DeFlora. 1978b. Metabolic deactlvatlon of hexavalent
chromium mutagenlcHy. Mutat. Res. 54: 139-147. (Cited 1n U.S. EPA, 1984)
Raffetto, G. 1977. Direct Interaction with cellular targets as the mecha-
nism for chromium carclnogenesls. Tumor1genes1s. 63: 503-512. (CHed 1n
U.S. EPA, 1984)
Royle, H. 1975. Toxldty of chromic add In the chromium plating Industry
(2). Environ. Res. 10: 141-163. (CHed 1n U.S. EPA, 1984)
Sano, T. and I. MHohara. 1978. Occupational cancer among chromium
workers. Jap. J. Chest Disorders. 37: 90-101. (CHed 1n U.S. EPA, 1984)
Sarto, F., I. Cemlnato, V. B1an1h1 and A.G. Lewis. 1982. Increased Inci-
dence of chromosomal aberrations and sister chromatld exchanges 1n workers
exposed to chromic acid (Cr03) 1n electroplating factories. Carclnogenesls
(London). 3: 1011-1016. (CHed 1n U.S. EPA, 1984)
Satoh, H., Y. Fukuda, K. Terll and N. Chlka Katsuno. 1981. Ep1dem1olog1c
study of workers engaged 1n the manufacturing of chromium compounds. J.
Occup. Med. 23(12: 835-838. (Cited In U.S. EPA, 1984)
-33-
-------
S1lverste1n, M., F. Mirer, D. Kotelchuck, B. S1verste1n and M. Bennett.
1981. Mortality among workers 1n a die-casting and electroplating plant.
Scand. J. Work Environ. Health. 7(4): 156-165. (Cited 1n U.S. EPA, 1984)
Stella, M., A. Mentaldl, R. Rossi, 6. Rossi and A.G. Levls. 1982. Clasto-
genlc effects of chromium on human lymphocytes \t± vitro and j_n vivo. Mutat.
Res. 101: 151-164. (Cited In U.S. EPA, 1984)
Steffee, C.H. and A.M. Baetjer. 1965. H1stopatholog1cal effects of chro-
mate chemicals. Report of studies 1n rabbits, guinea pigs, rats and mice.
Arch. Environ. Health. 11: 66. (Cited in U.S. EPA, 1984)
Stelnhoff, S., C. Gud, G.K. Hatfield and U. Mohr. 1983. Listing sodium
dlchromate and soluble calcium chromate for carcinogenicity 1n rats. Bayer
AG Institute of Toxicology. (Sept., Unpublished) (Cited 1n U.S. EPA, 1984)
Taylor, F.H. 1966. The relationship and duration of employment as reflect-
ed by a cohort of chromate workers. Am. J. Public Heath. 56: 218-229.
(Cited in U.S. EPA, 1984)
Todd, G.E. 1962. Tobacco manufacturer's standing committee research
papers. No. 1. Statistics of Smoking In the United Kingdom, 3rd ed.
Tobacco Research Council, London. (Cited 1n U.S. EPA, 1984)
-34-
-------
Towlll, I.E., C.R. Shrlner, J.S. Drury, A.S. Mammons and J.W. Holleman.
1978. Reviews of the environmental effects of pollutants: III. Chromium.
Prepared for Health Effects Research Laboratory, Office of Research and
Development, U.S. EPA, Cincinnati, OH. Report No. ORNL/EIS-80 and EPA
600/1-78-023. (Cited In U.S. EPA, 1984)
Tsuda, H. and K. Kato. 1977. Chromosomal aberrations and morphological
transformation 1n hamster embryonic cells treated with potassium dichromate.
Mutat. Res. 46: 87-94. (Cited In U.S. EPA, 1984)
Umeda, M. and M. N1sh1mura. 1979. Indudbllity of chromosomal aberrations
by metal compounds 1n cultured mammalian cells. Mutat. Res. 67: 221-229.
(Cited 1n U.S. EPA, 1984)
U.S. EPA. 1980a. Guidelines and Methodology Used 1n the Preparation of
Health Effects Assessment Chapters of the Consent Decree Water Quality
Criteria. Federal Register. 45: 79347-79357.
U.S. EPA. 1980b. Ambient Water Quality Criteria for Chromium. Environ-
mental Criteria and Assessment Office, Cincinnati, OH. EPA 440/5-80-035.
NTIS PB 81-117467.
U.S. EPA. 1983. Methodology and Guidelines for Reportable Quantity Deter-
minations Based on Chronic Toxicity Data. Prepared by the Environmental
Criteria and Assessment Office, Cincinnati, OH, OHEA for the Office of Solid
Waste and Emergency Response, Washington, DC.
-35-
-------
U.S. EPA. 1984. Health Assessment Document for Chromium. Environmental
Criteria and Assessment Office, Research Triangle Park, NC. EPA 600/8-83-
014F. NTIS PB 85-115905.
U.S. EPA. 1985. Acceptable Dally Intakes for Volatile Organic Chemicals,
Inorganic Chemicals and Synthetic Organic Chemicals. Criteria and Standards
Division, Office of Drinking Water. (Federal Register Draft)
Venltt, S. and L.S. Levy. 1974. Mutagenltlcy of chromates 1n bacteria and
Us relevance to chromate cardnogenesls. Nature. 250: 493-495. (Cited 1n
U.S. EPA, 1984)
V1gl1an1, E.C. and N. Zurlo. 1955. Efahrung der CUnlca del Lavoro m1t
elnlgen maxlmalen Arb1tsplatzkonzentrat1onen (MAk) von Industr1eg1ften.
Arch. Gewerbepath. Gewerbhyg. 13:528-534. (Ger.) (Cited In U.S. EPA, 1984)
Watanabe, S. and Y. Fukuchl. 1975. An ep1dem1olog1cal survey on lung
cancer 1n workers of a chromate-produdng Industry In Hokkaido, Japan.
Presented at International Congress on Occupational Health. (Cited 1n U.S.
EPA, 1984)
Weast, R.C., Ed. 1980. Handbook of Chemistry and Physics, 61st ed. CRC
Press, Boca Raton, FL. p. 873-166.
Wild, D. 1978. Cytogenetlc effects 1n the mouse of 17 chemical mutagens
and carcinogens evaluated by the mlcronucleus test. Mutat. Res. 56:
319-327. (Cited 1n U.S. EPA, 1984)
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APPENDIX
Summary Table for Hexavalent Chromium
Carcinogenic
Potency
Species
Experimental
Dose/Exposure
Effect
Reference
Inhalation
Oral
human
Carclnogenlclty
lung tumors
41 (mg/kg/day)
ND
U.S. EPA, 1984;
Mancuso, 1975
CO
~J
I
Route
Species
Experimental
Dose/Exposure
Effect
Acceptable Intake
(AIS or AIC)
Reference
Inhalation
AIS
AIC
Oral
AIS
AIC
rat
rat
Systemic Toxiclty
0-25 ppm In none
drinking water
for 1 year
(2.5 mg/kg)
0-25 ppm In none
drinking water
for 1 year
(2.5 mg/kg)
ND
ND
1.75 mg/day
0.35 mg/day
HacKenzle
et al.. 1958
HacKenzle
et al., 1958
ND = Not derivable
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