EPA-540/1-86-035
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
&EPA
HEALTH EFFECTS ASSESSMENT
FOR TRIVALENT CHROMIUM
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EPA/540/1-86-035
September 1984
HEALTH EFFECTS ASSESSMENT
FOR TRIVALENT CHROMIUM
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
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DISCLAIMER
This report has been funded wholly or In 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 trlvalent
chromium. All estimates of acceptable Intakes and carcinogenic potency
presented 1n 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/OATALOG 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. 1983b. Health Assessment Document for Chromium. Pre-
pared by the Environmental Criteria and Assessment Office, Research
Triangle Park, NC. External review draft. EPA 600/8-83-014A.
NITS PB 83-252205.
The Intent 1n these assessments Is 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 In
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 1n.concept to the ADI
(acceptable dally Intake). It 1s an estimate of an exposure level that
would not be expected to cause adverse effects when exposure occurs for a
significant portion of the Hfespan [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 1s 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 1n U.S. EPA (1983a).
For compounds for which there 1s sufficient evidence of cardnogenlcHy,
AIS and AIC values are not derived. For a discussion of risk assessment
methodology for carcinogens refer to U.S. EPA (1980a). Since cancer 1s a
process that 1s 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.
Data are limited concerning the toxlcologlcal effects of trlvalent
chromium salts. Trlvalent chromium appears to have a low order of toxldty,
presumably due to very poor absorption, especially following oral exposure.
Only one subchronlc study adequate for risk assessment was located.
Cr203 was administered 1n the diet of rats for 90 days at levels of 2%
and 5%. The estimated dally consumption of Cr(+3) Is 1373 mg/kg for the 5%
feeding level. Based on this, an AIS of 979 mg/day was calculated.
Adequate subchronlc Inhalation data were not located.
Again, only one chronic feeding study was found, conducted by the same
authors who reported the subchronlc Investigation. No adverse effects were
seen at the highest feeding level, 5%. The daily intake at this level is
estimated as 1467 mg Cr(+3)/kg. From these data, an AIC of 103 mg/day is
estimated.
Chronic Inhalation data were not located. An AIC of 0.357 mg Cr(+3)/day
is estimated based on the TLV. All of these estimates should be reviewed as
more complete data become available.
Data were not sufficient for derivation of a CS.
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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 wasvthe Project
Officer. The final documents In 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
v1
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TABLE OF CONTENTS
Page
1. ENVIRONMENTAL CHEMISTRY AND FATE 1
2. ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS 4
2.1. ORAL 4
2.2. INHALATION 4
3. TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS 5
3.1. SUBCHRONIC 5
3.1.1. Oral 5
3.1.2. Inhalation 5
3.2. CHRONIC.
3.2.1. Oral 7
3.2.2. Inhalation 7
3.3. TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS 8
4.
5.
3.4.
3.3.1. Oral
3.3.2. Inhalation
TOXICANT INTERACTIONS ,
CARCINOGENICITY- ,
4.1.
4.2.
4.3.
4.4.
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
REGULATORY STANDARDS AND CRITERIA
8
8
8
9
9
9
9
9
9
9
10
10
11
V11
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TABLE OF CONTENTS (cont.)
RISK
6.1.
6.2.
6.3.
ASSESSMENT
ACCEPTABLE INTAKE SUBCHRONIC (AIS)
6.1.1. Oral
6.1.2. Inhalation
ACCEPTABLE INTAKE CHRONIC (AIC)
6.2.1. Oral
6.2.2. Inhalation
6.2.3. Composite Score
CARCINOGENIC POTENCY (q-|*)
6.3.1. Oral ,
6.3.2. Inhalation ,
REFERENCES ,
Page
12
12
...... 12
12
12
12
13
13
14
14
14
15
APPENDIX: Summary Table for TMvalent Chromium ............ 21
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LIST OF ABBREVIATIONS
ADI Acceptable dally Intake
AIC Acceptable Intake chronic
AIS Acceptable Intake subchronlc
BCF B1oconcentrat1on factor
bw Body weight
CAS Chemical Abstract Service
CS Composite score
NOAEL No-observed-adverse-effect level
NOEL No-observed-effect level
TLV Threshold limit value
TWA Time-weighted average
1x
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1. ENVIRONMENTAL CHEMISTRY AND FATE
Chromium 1s a metallic element belonging to the First Transitional
Series of the periodic table. Elemental chromium has a CAS Registry number
of 7440-47-3. The three most stable forms In which chromium occurs 1n the
environment are 0 (metal and alloys), +3 and +6 valence states. In the +3
valence state, the chemistry of chromium 1s dominated by the formation of
stable hexa-coordlnated complexes with both organic and Inorganic Ugands
(Hartford, 1979). In the +6 valence state, chromium exists as oxo species
such as CrO- and CrO.21- that are strongly oxidizing (Cotton and
Wilkinson, 1980).
Chromium 1n the ambient air occurs from natural sources, Industrial and
product uses, and burning of fossil fuels and wood. The most Important
Industrial sources of chromium In the atmosphere originate from ferrochrome
production. Ore refining, chemical and refractory processing, cement
producing plants, automobile brake lining and catalytic converters for auto-
mobiles also contribute to the atmospheric burden for chromium (Flshbela,
1981). Chromate chemicals used as mist Inhibitors 1n cooling towers and the
mist formed during chrome plating are probably the primary sources of Cr(+6)
emitted as mists In the atmosphere (Towlll et a!., 1978).
Scarce Information exists 1n the literature regarding the nature of the
chemical species present 1n the atmosphere. Under normal conditions, Cr(+3)
and Cr(0) In the air should not undergo any reaction (Towlll et al., 1978).
Cr(+6) 1n air could eventually react with dust particles or other pollutants
to form Cr(+3) (NAS, 1974); however, the exact nature of such atmospheric
reactions has not been studied extensively. Chromium Is removed from air by
atmospheric fallout and precipitation (Flshbeln, 1981). The atmospheric
half-life for the physical removal mechanism 1s expected to depend on the
-1-
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particle size and particle density of atmospheric chromium. Chromium
particles of small aerodynamic diameter (<10 ym) may remain airborne for
long periods of time and may be transported great distances by wind currents
and diffusion forces.
Surface runoff, deposition from air, and release of municipal and Indus-
trial wastewaters are the sources of chromium In surface waters. The most
significant removal mechanism for Cr(+3) from the aquatic environment will
be precipitation as Cr 0 «xH 0 and eventually sedimentation of
C. O £
Cr~0~«xH_0. Cr(+6), however, may exist In aquatic media as a water
L. O C.
soluble complex anlon and may persist 1n water for a long time. Cr(+6) Is a
moderately strong oxidizing agent and will react with organic matter or
other reducing agents to form Cr(+3). Eventually, Cr(+3) will be precipi-
tated as Cr203«xH?0. Therefore, 1n surface water rich 1n organic
content, Cr(+6) will exhibit a much shorter lifetime (Callahan et a!., 1979).
Chromium probably occurs as the Insoluble Cr00«»xH00 In soil,
CO L.
given that organic matter 1n soil 1s expected to convert any soluble chro-
mate to Insoluble Cr-0- (U.S. EPA, 1983b). There 1s no known chemical
process that can cause chromium to be lost from soil. The primary processes
by which chromium Is lost from soil are physical. For example, chromium In
soil can be transported to the atmosphere by way of aerosol formation (U.S.
EPA, 1983b). Chromium 1s also transported from soil through runoff. Runoff
can remove both chromium Ions and bulk precipitates of chromium. In addi-
tion, flooding of soils and the subsequent anaerobic decomposition of plant
matter may Increase dissolution of Cr_0_ 1n soil through complexatlon
c O
(U.S. EPA, 1983b). The water soluble complexes may cause leaching of
chromium from soil. Page (1981) reported the detection of a small concen-
tration (1 yg/8. mean concentration) of chromium at a frequency of -100%
1n groundwater collected from New Jersey.
-2-
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The BCF for Cr(+6) in fish muscle appears to be <1.0, but values of 125
and 192 were obtained for oyster and blue mussel, respectively (U.S. EPA,
1980b). For Cr(+3), BCF values of 116, 153 and 86 were obtained with the
American oyster, soft shell clam and blue mussel (U.S. EPA, 1983b).
-3-
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2. ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS
2.1. ORAL
Donaldson and Barreras (1966) administered 51CrCl3 (chromium
chloride) orally to human patients. Based on fecal excretion of 51Cr,
absorption was -0.4%. When 51CrCl3 was administered Intraduodenally,
absorption was not appreciably changed.
In a number of animal studies, gastrointestinal absorption of trlvalent
chromium (as CrCl») was estimated to be <3% (Mertz et al., 1965; V1sek et
o
al., 1953; MacKenzle et al., 1959; Ogawa, 1976). Furthermore, Mertz et al.
(1965) reported that absorption In rats was Independent of the administered
dose and dietary history (deficient or supplemented 1n chromium).
2.2. INHALATION
Trlvalent chromium 1s absorbed very slowly by Inhalation. Baetjer et
al. (1959a) administered CrCK to guinea pigs Intratracheally. Ten
minutes post-treatment, 69% of the administered dose remained In the lungs,
while 4% was found 1n the blood and tissues. Percentages of administered
chromium found 1n the lungs 24 hours, 30 days and 60 days post-treatment
were 45, 30 and 12%, respectively. These Investigators hypothesized that
the slow absorption of trlvalent chromium (which 1s water soluble) 1s due to
the fact that 1t forms Insoluble complexes with macromolecules. Further-
more, gastrointestinal absorption following clearance from the respiratory
tract may be a factor when chromium compounds are administered by Inhala-
tion. V1sek et al. (1953) found similar results when 5aCrCl3 was
Instilled Intratracheally 1n guinea pigs. In this study, absorption from
the lungs was estimated to be -5%. There was also evidence of gastrointes-
tinal absorption because 55 and 7% of the administered 51Cr had been
recovered from the feces and urine, respectively, within 7 days.
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3. TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
3.1. SUBCHRONIC
3.1.1. Oral. Subchronlc studies regarding oral exposure to trlvalent
chromium are summarized 1n Table 3-1. The study by Akatsuka and Falrhall
(1934) cannot be used for quantitative risk assessment since the dose and
duration of exposure were not defined precisely. The study by MacKenzle et
al. (1958) suggests a NOEL at 25 ppm CrCl_, equivalent to 8.2 ppm trlva-
J
lent chromium. Assuming that an average rat weighs 0.35 kg and consumes
0.035 8. water/day, 8.2 ppm 1s adjusted to 0.82 mg trlvalent chromium/kg
bw/day.
The study by Ivankovlc and Preussman (1975) suggests a NOAEL of 5%
Cr-0. (50,000 ppm) based on depression of spleen and liver weights. The
c. O
authors calculated, based on measured food consumption and body weight, that
male rats 1n the 5% feeding group consumed 180 g/kg of Cr^O,, total over
the 88-day experimental period (discerned from body weight graph). This
corresponds to 1399 mg/kg/day of Cr(+3).
3.1.2. Inhalation. Only one subchronic animal study regarding exposure
to trlvalent chromium by inhalation was located 1n the available literature.
Akatsuka and Falrhall (1934) exposed two cats to chromium carbonate dust at
a level that varied from 3.3-83 mg/m3 (average = 58.3 mg/m3) for 86
sessions. Each session varied from 10-60 minutes, averaging 28 minutes for
one cat and 57 minutes for the other. No effects 1n terms of gross or
microscopic pathology were observed upon termination of the experiment.
Examination of control animals, 1f there were any, was not reported.
No human data that could be used in quantitative risk assessment of
inhalation exposure to trlvalent chromium were located in the available
literature.
-5-
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TABLE 3-1
Subchronlc Oral Toxlclty of Trlvalent Chromium
Species
Rat
Rat
Cat
Number
12 males, 9 females
b males, b females/
control; 14 males,
5 females/2%; 5 males,
10 females/5%
10
Compound Vehicle Dose
CrCl3 drinking 0, 25 ppm
water
Cr203 bread 0, 2, 5%
chromium feed 50-100
carbonate, mg/cat/day
chromium
phosphate
i
Duration Effects
12 months No change In body weight.
No changes In macroscopic
or microscopic pathology,
or clinical chemistry
variables.
5 days/week No effect on body weight,
for 90 days urologlcal or hematologl-
cal variables, or food
Intake. Slight reduction
In spleen and liver weights
at 2 and 5% levels.
1-3 months No effect on weights or
gross or microscopic
pathology of major organs.
Reference
HacKenzle
et al., 1958
Ivankovlc and
Preussman, 1915
Akatsuka and
Falrhall. 1934
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3.2. CHRONIC
3.2.1. Oral. Only one chronic study regarding oral exposure to tMvalent
chromium was located. Ivankovlc and Preussman (1975) fed 60 male and female
rats (per dose group) 0, 1, 2 or 5% Cr 0 baked 1n bread on 5 days/week
c O
for 600 feeding days (120 weeks). The authors estimated, based on measures
of food consumption and body weight, that rats consumed 360 g/kg bw, 720
g/kg bw and 1800 g/kg bw of total Cr 0 over the duration of the study
1n the 1, 2 and 5% Cr_0_ feeding groups, respectively. The highest dose
£ O
level (5%), which represented a total Cr_0- consumption for 600 days of
feeding of 1800 g/kg bw, corresponds to a total Cr (+3) Intake of 1232 g/kg
or 1467 mg/kg/day, expanding exposure over 840 days (600 days at 5 days/week
= 120 weeks or 840 days). Adverse effects were not noted at any feeding
level.
3.2.2. Inhalation. Exposure to vapors of chromium salts have been
suspected as a cause of asthma In occupatlonally-exposed workers. Until
recently, chromium specific 1mmunoglobul1n E antibodies had not been found
In affected workers to confirm the connection between chromium and asthma.
Recently, however, Novey et al. (1983) Identified chromium specific anti-
bodies In a 32-year-old white male worker who experienced a productive
cough, wheezing and dyspnea within 2 weeks of beginning a new job electro-
plating with chromium. Laboratory testing of this Individual was performed
with placebo, nickel and chromium solutions vaporized by heat. The nickel
and chromium solutions precipitated asthmatic symptoms Identical to those
experienced on the job. The authors concluded that the affected Individual
developed an acquired sensitivity to chromium and nickel vapors.
Pertinent data regarding chronic exposure of animals to tMvalent
chromium by Inhalation could not be located In the available literature.
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3.3. TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS
3.3.1. Oral. Pertinent data regarding the teratogenldty of orally
administered trlvalent chromium could not be located 1n the available
literature.
3.3.2. Inhalation. Pertinent data regarding the teratogenldty of
Inhaled trlvalent chromium could not be located 1n the available literature.
3.4. TOXICANT INTERACTIONS
Pertinent data regarding toxicant Interactions of trlvalent chromium
with other compounds could not be located 1n the available literature.
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4. CARCINOGENICITY
4.1. HUMAN DATA
4.1.1. Oral. Pertinent data regarding the cardnogenlcHy of orally
administered tMvalent chromium could not be located 1n the available
literature.
4.1.2. Inhalation. Occupational exposure to trlvalent chromium and other
chromium compounds by Inhalation has been studied 1n the chromate manufac-
turing and ferrochromlum Industries; however, exposures all Include mixed
exposures to both Cr(+3) and Cr(+6). The Cr(*6) species 1s the Hkely
etlologlcal agent In reports of excess cancer risk In chromium workers.
Data addressing exposures to Cr(+3) alone are not available.
4.2. BIOASSAYS
4.2.1. Oral. The results of several studies Indicate that trlvalent
chromium 1s not carcinogenic 1n mice or rats.
Schroeder et al. (1965) exposed 54 male and 54 female Swiss mice to
drinking water that contained 5 ppm chromium (as chromium acetate) for life.
No Increase In the Incidence of tumors was seen 1n the treated animals with
respect to controls. Similar results were obtained by Schroeder et al.
(1965) for Long-Evans rats.
Ivankovlc and Preussman (1975) fed chromium trloxlde 1n bread to 60 male
and female rats at levels of 1, 2 or 5%, 5 days/week for 2 years. No
difference was seen between controls and treated animals with respect to
tumor Incidence.
4.2.2. Inhalation. Several animal studies Indicate that trlvalent
chromium compounds are not carcinogenic when administered by Inhalation,
either by natural routes (Baetjer et al., 1959a), Intrapleural Injection
(Baetjer et al., 1959b; Hueper and Payne, 1962) or 1ntrabronch1al Implanta-
tion (Levy and Venitt, 1975; Levy and Martin, 1983).
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4.3. OTHER RELEVANT DATA
In general, trlvalent chromium was not mutagenlc 1n bacterial assays
when tested with or without a mammalian activation system (Venitt and Levy,
1974; PetrllH and Deflora, 1977, 1978a,b). In one study, trlvalent chro-
mium was mutagenlc in Bacillus subtllis. but this activity was low compared
with compounds of hexavalent chromium (Nakamuro et al., 1978).
There is conflicting information with regard to the ability of trlvalent
chromium to interact with DNA. Compounds of trlvalent chromium were found
to be clastogenic in BALB/c cells as CrCl3 (Raffetto, 1977), CHO cells as
CrCl3, Cr(N03)3, KCr(S04)2 or Cr(CH3COO)3 (Levis and Majone,
1979), Don Chinese hamster cells as hydrated CrCl3 (Ohno et al., 1982) and
in cultured human leukocytes as Cr(CH_COO)/, (Nakamuro et al., 1978), but
•J 3
not in mouse FM3A cells as Cr2(S04)3 (Umeda and Nishimura, 1979),
cultured human leukocytes as CrCK or Cr(NOJ,, (Nakamuro et al., 1978)
0 O >J —
or Don Chinese hamster cells as Cr_(SOJ, (Ohno et al., 1982).
L. *r -J
4.4. WEIGHT OF EVIDENCE
IARC (1980) concluded that animal data are inadequate for the evaluation
of the carcinogenlcity of Cr(+3) compounds. Furthermore, although there 1s
sufficient evidence of respiratory carcinogenidty associated with exposure
to chromium, the relative contributions of Cr(+3), Cr(f6), metallic chromium
or soluble versus insoluble chromium to carcinogenicity cannot be elucidated.
Applying the criteria for evaluating the overall weight of evidence for
carcinogenicity to man proposed by the Carcinogen Assessment Group of the
U.S. EPA (Federal Register, 1984), trlvalent chromium 1s most appropriately
designated a Group D - Not Classified material.
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5. REGULATORY STANDARDS AND CRITERIA
The ACGIH (1983) has recommended a TLV-TWA of 0.5 mg/m3 for occupa-
tional exposure to tMvalent chromium. This level was established 1n order
to minimize toxic effects and to protect against pulmonary disease.
The U.S. EPA (1982) has established a criterion of 59 mg/a. for trlva-
lent chromium 1n water. This Is derived from the Interim ADI of 125 mg/man/
day (see Section 3.1.1.) (Ivankovlc and Preussman, 1975).
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6. RISK ASSESSMENT
6.1. ACCEPTABLE INTAKE SUBCHRONIC (AIS)
6.1.1. Oral. Based on the study by Ivankovlc and Preussman (1975), the
NOAEL of 1399 mg tMvalent chromium/kg bw/day for depression of spleen and
liver weights 1n rats can be used to calculate an AIS. Dividing 1399 mg/kg/
day by an uncertainty factor of 100 (10 to account for the range of sensi-
tivities In the human population, 10 for extrapolating from animal data to
humans), an AIS of 13.99 mg/kg/day 1s established for Ingestlon of tMvalent
chromium. Assuming an average human weighs 70 kg, this 1s equivalent to 979
mg/man/day.
6.1.2. Inhalation. Only one study (Akatsuka and Falrhall, 1934) regard-
Ing the effects of subchronlc Inhalation of trlvalent chromium was located
1n the available literature. Only two cats were exposed, however, and
neither the doses nor the durations of exposure were precisely defined;
therefore, these data cannot be used 1n quantitative risk assessment.
6.2. ACCEPTABLE INTAKE CHRONIC (AIC)
6.2.1. Oral. The NOEL of 5% Cr00. [1467 mg Cr(+3)/kg bw/day calcu-
£ 0
lated from measured food and body weight factors] derived from the chronic
study by Ivankovlc and Preussman (1975) on rats can be used as the basis for
the calculation of an AIC. Dividing the NOEL of 1467 mg/kg/day by an uncer-
tainty factor of 1000 (10 to account for the range of sensitivities In the
human population; 100 for extrapolating from animal studies to humans and
because effects seen In the subchronlc study were not specifically addressed
In the chronic study), an AIC of 1.467 mg/kg bw/day is established for
trlvalent chromium. Assuming an average human body weight of 70 kg, this Is
equivalent to 103 mg/man/day.
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This value differs from the ADI of 125 mg/man/day derived by the U.S.
EPA (1982) from the Ivankovlc and Preussman (1975) study because the U.S.
EPA (1980b) did not convert ppm Cr203 to ppm trlvalent chromium, and
used standard reference values for the rat for food consumption and body
weight 1n Heu of figures reported In Ivankovlc and Preussman (1975).
6.2.2. Inhalation. Since quantitative chronic exposure studies regarding
Inhalation of trlvalent chromium were not located 1n the available litera-
ture, an AIC may be calculated from the TLV of 0.5 mg/m3 established by
the AC6IH (1983). Adjusting to units of mg/man/day, 0.5 mg/m3 x 5/7 days/
week x the average work day human Inhalation rate (10 mVday) = 3.57
mg/man/day. Dividing 3.57 mg/man/day by an uncertainty factor of 10 (to
account for the range of sensitivities 1n the human population), an AIC of
0.357 mg/man/day 1s established for chronic Inhalation of trlvalent chromium.
6.2.3. Composite Score. U.S. EPA (1983c) calculated CSs for chromium and
compounds using data from two Inhalation and two oral studies. These
experiments were conducted with hexavalent forms of chromium. U.S. EPA
(1983c) also reviewed the study 1n rats 1n which a slight reduction 1n
spleen and Hver weights was observed 1n animals fed bread containing
Cr.O- for 90 days (Ivankovlc and Preussman, 1975). Since similar signs
L. *3
did not appear 1n rats treated with Cr^O- containing bread for 2 years
(Ivankovlc and Preussman, 1975), the toxlcologlcal significance of the
apparent effects on liver and spleen weights In the subchronlc study was
questionable and a CS was not derived from these data (U.S. EPA, 1983c). No
other studies with trlvalent chromium were found from which a CS could be
calculated. Therefore, In their review of the data base for trlvalent
chromium, U.S. EPA (1983a) calculated no CSs based on studies with trlvalent
chromium.
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6.3. CARCINOGENIC POTENCY (q.,*)
6.3.1. Oral. IARC (1980) has concluded that animal data are Inadequate
for the evaluation of the carclnogenlcHy of Cr(+3) compounds. The two oral
studies located 1n the available literature (Schroeder et a!., 1965;
Ivankovlc and Preussman, 1975) reported negative results for rats and mice.
6.3.2. Inhalation. Data are Inadequate for the evaluation of the
carclnogenlcHy of Cr(+3) compounds. Animal studies have been negative
(Baetjer et al., 1959a,b; Hueper and Payne, 1962; Levy and Venltt, 1975;
Levy and Martin, 1983).
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7. REFERENCES
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20: 124-135. (Cited 1n U.S. EPA, 1983b)
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vironmental fate of 129 priority pollutants. Vol. I. Office of Water
Planning and Standards, Office of Water and Waste Management, U.S. EPA,
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Cotton, F.A. and G. Wilkinson. 1980. Advanced Organic Chemistry. A
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Donaldson, R.M. and R.F. Barreras. 1966. Intestinal absorption of trace
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Hueper, W.C. and W.W. Payne. 1962. Experimental studies In metal cardno-
genesls — Chromium, nickel, Iron, arsenic. Arch. Environ. Health. 5:
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metals and metallic compounds. WHO, IARC, Lyon, France. Vol. 23,
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effects after administrations of high doses of chronic oxide pigment 1n sub-
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Levls, A.6. and F. Majone. 1979. Cytotoxlc and clastogenlc effects of
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studies of chromosomal aberration and mutagenldty of tMvalent and hexa-
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NAS (National Academy of Sciences). 1974. Medical and Biological Effects
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Petrim, F.L. and S. DeFlora. 1978b. Metabolic deactlvatlon of hexavalent
chromium mutagenlcHy. Mutat. Res. 54: 139-147. (Cited In U.S. EPA, 19835)
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U.S. EPA. 1982. Errata for Ambient Water Quality Criteria Documents, Feb.
23, 1982 update. Prepared by the Environmental Criteria and Assessment
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minations Based on Chronic Tox1c1ty Data. Prepared by the Environmental
Criteria and Assessment Office, Cincinnati, OH, OHEA for the Office of Solid
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APPENDIX
Summary Table for TMvalent Chromium
Species
Experimental
Dose/Exposure
Effect
Acceptable Intake
(AIS or AIC)
Reference
Inhalation
AIS
AIC
Oral
^ AIS
—J
I
AIC
Maximum
composite
score
human
rat
rat
TLV-TWA =0.5 mg/m3
5% Cr203 = NOAEL
5%
= NOEL
none
slight reduction
In liver and
spleen weights
none
ND
0.357 mg/man/day ACGIH. 1983
979 mg/man/day
103 mg/man/day
ND
Ivankovlc and
Preussman, 1975
Ivankovlc and
Preussman, 1975
U.S. EPA, 1983a
ND = Not derived
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