CASRN 18540-29-9
09/03/1998
Contents
- INHALATION EXPOSURE (RfC)
I.A. REFERENCE DOSE FOR CHRONIC ORAL EXPOSURE (RfD)
I.B. REFERENCE CONCENTRATION FOR CHRONIC
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Note: A TOXICOLOGICAL REVIEW is available for this chemical |
0144
Chromium(VI); CASRN 18540-29-9; 09/03/1998
Health assessment information on a chemical substance is included in IRIS
only after a comprehensive review of chronic toxicity data by U.S. EPA health
scientists from several Program Offices, Regional Offices, and the Office of
Research and Development. The summaries presented in Sections I and II represent
a consensus reached in the review process. Background information and
explanations of the methods used to derive the values given in IRIS are provided
in the Background Documents.
STATUS OF DATA FOR Chromium(VI)
File First On-Line 03/31/1987
Category (section) Status Last Revised
Oral RfD Assessment (I.A.) On-line 09/03/1998
Inhalation RfC Assessment (I.B.) On-line 09/03/1998
Carcinogenicity Assessment (II.) On-line 09/03/1998
Conversion Factors and Assumptions -- Drinking water consumption = 0.1 L/kg-day
(reported).
_I. CHRONIC HEALTH HAZARD ASSESSMENTS FOR NONCARCINOGENIC EFFECTS
__I.A. REFERENCE DOSE FOR CHRONIC ORAL EXPOSURE (RfD)
Chromium(VI)
CASRN -- 18540-29-9
Last Revised -- 09/03/1998
The oral Reference Dose (RfD) is based on the assumption that thresholds
exist for certain toxic effects such as cellular necrosis. It is expressed in
units of mg/kg-day. In general, the RfD is an estimate (with uncertainty
spanning perhaps an order of magnitude) of a daily exposure to the human
population (including sensitive subgroups) that is likely to be without an
appreciable risk of deleterious effects during a lifetime. Please refer to the
Background Document for an elaboration of these concepts. RfDs can also be
derived for the noncarcinogenic health effects of substances that are also
carcinogens. Therefore, it is essential to refer to other sources of information
concerning the carcinogenicity of this substance. If the U.S. EPA has evaluated
this substance for potential human carcinogenicity, a summary of that evaluation
will be contained in Section II of this file.
___I.A.1. ORAL RfD SUMMARY
Critical Effect Experimental Doses* UF MF RfD
None reported NOAEL: 25 mg/L of chromium 300 3 3E-3 mg/kg-day
as K2CrO4
2.5 mg/kg-day (adj.)
LOAEL: None
Rat, 1-year drinking study
MacKenzie et al., 1958
*Conversion Factors and Assumptions -- Drinking water consumption = 0.1 L/kg-day
(reported).
___I.A.2. PRINCIPAL AND SUPPORTING STUDIES (ORAL RfD)
MacKenzie, RD; Byerrum, RU; Decker, CF, et al. (1958) Chronic toxicity studies. II.
Hexavalent and trivalent chromium administered in drinking water to rats. Am Med
Assoc Arch Ind Health 18:232-234.
Groups of eight male and eight female Sprague-Dawley rats were supplied with
drinking water containing 0.45-11.2 ppm (0.45-11.2 mg/L) hexavalent chromium
(as K2CrO4) for 1 year. The control group (10/sex) received distilled water.
A second experiment involved three groups of 12 male and 9 female rats. One group
was given 25 ppm (25 mg/L) chromium (as K2CrO4), a second received 25 ppm chromium
in the form of chromic chloride, and the controls again received distilled
water. No significant adverse effects were seen in appearance, weight gain, or
food consumption, and there were no pathologic changes in the blood or other tissues
in any treatment group. The rats receiving 25 ppm of chromium (as K2CrO4) showed an
approximate 20% reduction in water consumption. Based on the body weight
of the rat (0.35 kg) and the average daily drinking water consumption for the rat
(0.035 l/day), this dose can be converted to give an adjusted NOAEL of 2.5 mg/kg-day
chromium(VI).
For rats treated with 0-11 ppm (in drinking water), blood was examined
monthly, and tissues (livers, kidneys, and femurs) were examined at 6 mo and 1
year. Spleens were also examined at 1 year. The 25 ppm groups (and
corresponding controls) were examined similarly, except that no animals were
killed at 6 mo. An abrupt rise in tissue chromium concentrations was noted in
rats treated with more than 5 ppm. The authors stated that "apparently,
tissues can accumulate considerable quantities of chromium before pathological
changes result." In the 25 ppm treatment groups, tissue concentrations of
chromium were approximately 9 times higher for those treated with hexavalent
chromium than for the trivalent group. Similar no-effect levels have been
observed in dogs. Anwar et al. (1961) observed no significant effects in
female dogs (2/dose group) given up to 11.2 ppm chromium(VI)
(as K2CrO4) in drinking water for 4 years. The calculated
doses were 0.012-0.30 mg/kg of chromium(VI).
___I.A.3. UNCERTAINTY AND MODIFYING FACTORS (ORAL RfD)
UF = 300.
The uncertainty factor of 300 represents two 10-fold decreases in dose to
account for both the expected interhuman and interspecies variability in the
toxicity of the chemical in lieu of specific data, and an additional factor of
3 to compensate for the less-than-lifetime exposure duration of the principal study.
MF = 3.
The modifying factor of 3 is to account for concerns raised by the study of
Zhang and Li (1987).
___I.A.4. ADDITIONAL STUDIES/COMMENTS (ORAL RfD)
This RfD is limited to soluble salts of hexavalent chromium. Examples of
soluble salts include potassium dichromate (K2Cr2O7), sodium dichromate
(Na2Cr2O7), potassium chromate (K2Cr2O4), and sodium chromate (Na2CrO4).
Trivalent chromium is an essential nutrient. There is evidence to indicate that
hexavalent chromium is reduced in part to trivalent chromium in vivo (Petrilli
and DeFlora, 1977, 1978; Gruber and Jennette, 1978).
In 1965, a study of 155 subjects exposed to drinking water at concentrations
of approximately 20 mg/L was conducted outside Jinzhou, China. Subjects were
observed to have sores in the mouth, diarrhea, stomachache, indigestion, vomiting,
elevated white blood cell counts with respect to controls, and a higher per capita
rate of cancers, including lung cancer and stomach cancer. Precise exposure
concentrations, exposure durations, and confounding factors were not discussed, and
this study does not provide a NOAEL for the observed effects. However, the study
suggests that gastrointestinal effects may occur in humans following exposures to
hexavalent chromium at levels of 20 ppm in drinking water (Zhang and Li, 1987).
Zahid et al. (1990) fed BALB/C albino Swiss mice trivalent (chromium
disulfate) and hexavalent (potassium dichromate) chromium at concentrations of 100,
200, and 400 ppm for 35 days in the diet. The author concluded that a small but
significant increase of hexavalent chromium in the testes of fed animals induced
significant degeneration. The National Toxicology Program (1996a,b, 1997) recently
conducted a three-part study to investigate the potential reproductive toxicity of
hexavalent chromium in rats and mice. The study included oral administration of
potassium dichromate in Sprague-Dawley rats, a repeat of the study of Zahid et
al. (1990) using BALB/C mice, and a reproductive assessment by continuous breeding
study in BALB/C mice. The reproductive assessment indicated that potassium
dichromate administered at 15-400 ppm in the diet is not a reproductive toxicant in
either sex of BALB/C mice or Sprague-Dawley rats.
Several reports of possible fetal damage caused by chromium compounds were
located in the literature. High doses (250-1,000 ppm) of orally administered
chromium (VI) compounds have been reported to cause developmental toxicity in mice
(Trivedi et al., 1989). The authors observed significant increases in
preimplantation and postimplantation losses and dose-dependent reductions in total
weight and crown-rump length in the lower dose groups. Additional effects
included treatment-related increases in abnormalities in the tail and wrist
forelimbs, and subdermal hemorrhagic patches in the offspring.
Junaid et al. (1996) and Kanojia et al. (1996) exposed female Swiss albino
mice and female Swiss albino rats, respectively, to 250, 500, or 750 ppm potassium
dichromate in drinking water to determine the potential embryotoxicity of
hexavalent chromium during days 6-14 of gestation. The authors reported retarded
fetal development and embryo- and fetotoxic effects including reduced fetal weight,
reduced number of fetuses (live and dead) per dam, and higher incidences of
stillbirths and post-implantation loss in the 500 and 750 ppm dosed mothers.
Significantly reduced ossification in bones was also observed in the medium- and
high-dose groups. Based on the body weight and the drinking water ingested by the
animals in the 250 ppm dose group, the exposure levels in the 250 ppm groups can be
identified as 67 mg/kg-day and 37 mg/kg-day in mice and rats, respectively.
The Junaid et al. (1996) and Kanojia et al. (1996) studies utilized doses
approximately 10-fold higher than those used in Mackenzie et al (1958), but neither
of the reproductive studies identified a clear NOAEL for the embryotoxic effects of
hexavalent chromium. On the basis of the body weight and the drinking water
ingested by the animals in the low-dose groups (250 ppm), the LOAELs of
67 mg/kg-day and 37 mg/kg-day can be identified from Junaid et al. (1996) and
Kanojia et al. (1996) in mice and rats, respectively. Application of 10-fold
uncertainty factor to extrapolate from LOAELs to NOAELs in these studies would
generate NOAELs of 6.7 mg/kg-day and 3.7 mg/kg-day, respectively. These
extrapolated NOAEL values are similar to, and support the use of, the NOAEL of 2.5
mg/kg-day identified from the study of MacKenzie et al. (1958) for development of
the reference dose.
Elbetieha and Al-Hamood (1997) reported impacts on fertility following
potassium dichromate exposures in mice; however, many of the observed effects did
not occur in a clear dose-dependent fashion. The authors did not indicate the
amount of water ingested by the animals, and stated only that water ingestion was
reduced in the treatment groups relative to the controls.
Chromium is one of the most common contact sensitizers in males in
industrialized countries and is associated with occupational exposures to numerous
materials and processes, including chrome plating baths, chrome colors and dyes,
cement, tanning agents, wood preservatives, anticorrosive agents, welding fumes,
lubricating oils and greases, cleaning materials, and textiles and furs (Burrows
and Adams, 1990; Polak et al., 1973). Solubility and pH appear to be the primary
determinants of the capacity of individual chromium compounds to elicit an allergic
response (Fregert, 1981; Polak et al., 1973). The low solubility chromium (III)
compounds are much less efficient contact allergens than chromium (VI) (Spruit and
van Neer, 1966).
Dermal exposure to chromium has been demonstrated to produce irritant and
allergic contact dermatitis (Bruynzeel et al., 1988; Polak, 1983; Cronin, 1980;
Hunter, 1974). Primary irritant dermatitis is related to the direct cytotoxic
properties of chromium, while allergic contact dermatitis is an inflammatory
response mediated by the immune system. Allergic contact dermatitis is a cell-
mediated immune response that occurs in a two-step process. In the first step
(induction), chromium is absorbed into the skin and triggers an immune response
(sensitization). Sensitized individuals will exhibit an allergic dermatitis
response when exposed to chromium above a threshold level (Polak, 1983). Induction
is generally considered to be irreversible. Concentrations of hexavalent chromium
in environmental media that are protective of carcinogenic and noncarcinogenic
effects are likely to be lower than the concentrations required to cause induction
of allergic contact dermatitis. However, these concentrations may not be lower
than concentrations required to elicit an allergic response in individuals who have
been induced.
The RfD was updated in 1998. The RfD is similar to the previous value on IRIS
but now incorporates a threefold uncertainty factor to account for the
less-than-lifetime exposure in the principal study and a threefold modifying factor
to account for uncertainties related to reports of gastrointestinal effects
following drinking water exposures in a residential population in China.
___I.A.5. CONFIDENCE IN THE ORAL RfD
Study -- Low
Database -- Low
RfD -- Low
The overall confidence in this RfD assessment is low. Confidence in the
chosen study is low because of the small number of animals tested, the small number
of parameters measured, and the lack of toxic effect at the highest dose tested.
Confidence in the database is low because the supporting studies are of
equally low quality and the developmental toxicity endpoints are not well studied.
___I.A.6. EPA DOCUMENTATION AND REVIEW OF THE ORAL RfD
Source Document -- U.S. EPA, 1998
This assessment was peer reviewed by external scientists. Their comments have
been evaluated carefully and incorporated in finalization of this IRIS summary. A
record of these comments is included as an appendix to the Toxicological Review of
Hexavalent Chromium in support of Summary Information on the Integrated Risk
Information System (IRIS) (U.S. EPA, 1998).
Other EPA Documentation --
U.S. EPA. (1984) Health effects assessment for hexavalent chromium. Prepared by
the Office of Health and Environmental Assessment, Environmental Criteria and
Assessment Office, Cincinnati, OH, for the Office of Solid Waste and Emergency
Response, Washington, DC.
U.S. EPA. (1985) Drinking water health advisory for chromium. Prepared by the
Office of Health and Environmental Assessment, Environmental Criteria and
Assessment Office, Cincinnati, OH, for the Office of Drinking Water, Washington, DC
(Draft).
Agency consensus date -- 04/28/1998
___I.A.7. EPA CONTACTS (ORAL RfD)
Please contact the Risk Information Hotline for all questions concerning this
assessment or IRIS, in general, at (513) 569-7254 (phone), (513) 569-7159 (fax), or
RIH.IRIS@EPAMAIL.EPA.GOV (Internet address).
__I.B. REFERENCE CONCENTRATION FOR CHRONIC INHALATION EXPOSURE
(RfC)
Chromium(VI)
CASRN -- 18540-29-9
Last Revised -- 09/03/1998
The inhalation reference concentration (RfC) is analogous to the oral RfD and
is likewise based on the assumption that thresholds exist for certain toxic effects
such as cellular necrosis. The inhalation RfC considers toxic effects for both the
respiratory system (portal-of-entry) and for effects peripheral to the respiratory
system (extrarespiratory effects). It is generally expressed in units of mg/m3.
In general, the RfC is an estimate (with uncertainty spanning perhaps an order of
magnitude) of a daily inhalation exposure of the human population (including
sensitive subgroups) that is likely to be without an appreciable risk of
deleterious effects during a lifetime. Inhalation RfCs were derived according to
the Interim Methods for Development of Inhalation Reference Doses (U.S. EPA, 1989)
and subsequently, according to Methods for Derivation of Inhalation Reference
Concentrations and Application of Inhalation Dosimetry (U.S. EPA, 1994). RfCs can
also be derived for the noncarcinogenic health effects of substances that are
carcinogens. Therefore, it is essential to refer to other sources of information
concerning the carcinogenicity of this substance. If the U.S. EPA has evaluated
this substance for potential human carcinogenicity, a summary of that evaluation
will be contained in Section II of this file.
___I.B.1. INHALATION RfC SUMMARY
Critical Effect Experimental Doses* UF MF RfC
(1) Chromic acid mists and dissolved Cr (VI) aerosols:
Nasal septum atrophy NOAEL: none 90 1 8E-6 mg/m3
LOAEL: 2E-3 mg/m3
7.14 E-4 mg/m3 (adj.)
Human subchronic
occupational study
Lindberg and Hedenstierna, 1983
(2) Cr(VI) particulates:
Lactate dehydrogenase in BMD: 0.016 mg/m3 300 1 1E-4 mg/m3
bronchioalveolar lavage fluid 0.034 mg/m3 (adj.)
Rat subchronic study
Glaser et al., 1990
Malsch et al., 1994
*Conversion Factors and Assumptions -- Breathing rate for 8-hour occupational
exposure = 10 m3; breathing rate for 24-hour continuous exposure = 20 m3;
occupational exposure = 5 days/week; continuous exposure = 7 days/week. RDDR
(regional deposited dose ratio for particulates to account for differences between
rats and humans) = 2.16
Nasal mucosal irritation, atrophy, and perforation have been widely reported
following occupational exposures to chromic acid mists and dissolved hexavalent
chromium aerosols. However, there is uncertainty regarding the relevance of
occupational exposures to chromic acid mists and dissolved hexavalent chromium
aerosols to exposures to Cr(VI) dusts in the environment. Lower respiratory
effects have been reported in laboratory animals following exposures to Cr(VI)
dusts. However, these studies have not reported on nasal mucosal effects
following the exposures. The uncertainties in the database have been addressed
through the development of two RfCs; one based on nasal mucosal atrophy following
occupational exposures to chromic acid mists and dissolved hexavalent chromium
aerosols, and a second based on lower respiratory effects following inhalation of
Cr(VI) particulates in rats.
___I.B.2. PRINCIPAL AND SUPPORTING STUDIES (INHALATION RfC)
(1) Chromic acid mists and dissolved Cr (VI) aerosols
Three studies have focused on nasal mucosal irritation, atrophy, and
perforation following occupational exposures to chromic acid mists (Cohen et al.,
1974; Lucas and Kramkowski, 1975; Lindberg and Hedenstierna, 1983). Of these, the
study of Lindberg and Hedenstierna provides the most information on exposure levels
and symptoms reported by exposed workers. Respiratory symptoms, lung function, and
changes in nasal septum were studied in 104 workers (85 males, 19 females) exposed
in chrome plating plants. Workers were interviewed using a standard questionnaire
for the assessment of nose, throat, and chest symptoms. Nasal inspections and
pulmonary function testing were performed as part of the study.
The median exposure time for the entire group of exposed subjects (104) in the
study was 4.5 years (0.1-36 years). A total of 43 subjects exposed almost
exclusively to chromic acid experienced a mean exposure time of 2.5 years (0.2-23.6
years). The subjects exposed almost exclusively to chromic acid were divided into
a low-exposure group (8-hr TWA below 0.002 mg/m3, N=19) and a high-exposure group
(8-hr TWA above 0.002 mg/m3, N=24). Exposure measurements using personal air
samplers were performed for 84 subjects in the study on 13 different days.
Exposure for the remaining 20 workers was assumed to be similar to that measured
for workers in the same area. Nineteen office employees were used as controls for
nose and throat symptoms. A group of 119 auto mechanics whose lung function had
been evaluated by similar techniques was selected as controls for lung function
measurements. Smoking habits of workers were evaluated as part of the study.
At mean exposures below 0.002 mg/m3, 4/19 workers from the low-exposure group
of subjective nasal symptoms. Atrophied nasal mucosa were reported in 4/19
subjects from this group and 11/19 had smeary and crusty septal mucosa, which was
statistically higher than controls. No one exposed to levels below 0.001 mg/m3
complained of subjective symptoms. At mean concentrations of 0.002 mg/m3 or above,
approximately one-third of the subjects had reddened, smeary, or crusty nasal
mucosa. Atrophy was seen in 8/24 workers, which was significantly different from
controls. Eight subjects had ulcerations in the nasal mucosa and five had
perforations of the nasal septum. Atrophied nasal mucosa was not observed in any
of the 19 controls, but smeary and crusty septal mucosa occurred in 5/19 controls.
Short-term effects on pulmonary function were evaluated by comparing results
of tests taken on Monday and Thursday among exposed groups and controls. No
significant changes were seen in the low-exposure group or the control group.
Nonsmokers in the high-exposure group experienced significant differences in
pulmonary function measurements from the controls, but the results were within
normal LIMITS.
The authors concluded that 8-hour mean exposures to chromic acid above 0.002
mg/m3 may cause a transient decrease in lung function, and that short-term
exposures to greater than 0.02 mg/m3 may cause septal ulceration and perforation.
Based on the results of this study, a LOAEL of 0.002 mg/m3 can be identified for
incidence of nasal septum atrophy following exposure to chromic acid mists in
chromeplating facilities. At TWA exposures greater than 0.002 mg/m3, nasal septum
ulceration and perforations occurred in addition to the atrophy reported at lower
concentrations. The LOAEL is based on an 8-hour TWA occupational exposure. The
LOAEL is adjusted to account for continuous exposure according to the following
equation:
LOAELc = 0.002 mg/m3 x (MVho/MVh) x 5 days/7 days
where:
LOAELc is the LOAEL for continuous exposure
MVho is the breathing volume for an 8 hour occupational exposure (10 m3)
MVh is the breathing volume for a 24 hour continuous exposure (20 m3)
The LOAEL of 0.002 mg/m3 based on a TWA exposure to chromic acid is converted
to a LOAEL for continuous exposure of 7.14 E-4 mg/m3. An uncertainty factor of 3
is applied to the LOAEL to extrapolate from a subchronic to a chronic exposure, an
uncertainty factor of 3 is applied to account for extrapolation from a LOAEL to a
NOAEL, and an uncertainty factor of 10 is applied to the LOAEL to account for
interhuman variation. The total uncertainty factor applied to the LOAEL is 90.
Application of the uncertainty factor of 90 to the LOAEL of 7.14E-4 mg/m3
generates an RfC of 8 E-6 mg/m3 for upper respiratory effects caused by chromic
acid mists and dissolved hexavalent chromium aerosols.
(2) Cr (VI) Particulates:
Two studies provide high-quality data on lower respiratory effects following
exposures to chromium particulates (Glaser et al., 1985, 1990). Glaser et al.
(1990) exposed 8-week-old male Wistar rats to sodium dichromate at 0.05 - 0.4 mg
Cr(VI)/m3 22 hr/day, 7 days/wk for 30-90 days. Chromium-induced effects occurred
in a strong dose-dependent manner. The authors observed obstructive respiratory
dyspnea and reduced body weight following subacute exposure at the higher dose
levels. The mean white blood cell count was increased at all doses (p < 0.05)
and was related to significant dose-dependent leukocytosis following subacute
exposures. Mean lung weights were significantly increased at exposure levels of
0.1 mg/m3 following both the subacute and subchronic exposures. Accumulation of
macrophages was seen in all of the exposure groups and was postulated to be a
chromium-specific irritation effect that accounted for the observed increases in
lung weights. Focal inflammation was observed in the upper airways following the
subchronic exposure, and albumin and lactate dehydrogenase (LDH) in
bronchioalveolar lavage fluid (BALF) were increased following the exposure. The
authors concluded that chromium inhalation induced pneumocyte toxicity and
suggested that inflammation is essential for the induction of most chromium
inhalation effects and may influence the carcinogenicity of Cr(VI) compounds.
Glaser et al. (1985) exposed 5-week-old male Wistar rats to aerosols of sodium
dichromate at concentrations ranging from 0.025 to 0.2 mg Cr(VI)/m3, 22 hr/day in
subacute (28 day) or subchronic (90 day) protocols. Chromium-induced effects
occurred in a dose-dependent manner. Lung and spleen weights were significantly
increased (p < 0.005) after both subacute and subchronic exposures at
concentrations greater than 0.025 mg/m3. Differences in the mean total serum
immunoglobulin were also significant at exposures above 0.025 mg/m3, while
exposures to aerosol concentrations greater than 0.1 mg/m3 resulted in depression
of the immune system stimulation. The immune stimulating effect of subchronic
exposure was not reversed after 2 mo of fresh air regeneration. Bronchoalveolar
lavage (BAL) cell counts were significantly decreased following subchronic exposure
to levels above 0.025 mg/m3 chromium. The number of lymphocytes and granulocytes
showed a slight but significant increase in the lavage fluids of the subacute and
subchronically exposed groups. At subacute exposure concentrations up to 0.05
mg/m3 the phagocytic activity of the alveolar macrophages increased; however,
subchronic exposure at 0.2 mg/m3 decreased this function significantly. The spleen
T-lymphocyte subpopulation was stimulated by subchronic exposure to 0.2 mg/m3
chromium, and serum contents of triglycerides and phospholipids differed
significantly from controls (p < 0.05) at this concentration.
Together, these studies provide useful information on chromium exposure-
related impacts including lung and spleen weight, LDH in BALF, protein in BALF, and
albumin in BALF. The cellular content of BALF is considered representative of
initial pulmonary injury and chronic lung inflammation, which may lead to the onset
of pulmonary fibrosis (Henderson, 1988). While these studies present
dose-dependent results on sensitive indicators of lower respiratory toxicity,
potential upper respiratory impacts resulting from the exposures were not
addressed. Glaser et al. (1990) state that the upper respiratory tract was
examined, but these data were not reported.
One approach for development of an RfC using the data of Glaser et al. (1985,
1990) was offered by Malsch et al. (1994), who generated an inhalation RfC for
chromium dusts using a benchmark concentration (BMC) approach. The Agency
developed its RfC for particulates based on this approach. After excluding
exposures for periods of less than 90 days from the BMC analysis, Malsch et al.
(1994) developed BMCs for lung weight, LDH in BALF, protein in BALF, albumin in
BALF, and spleen weight. The Malsch et al. (1994) analysis defined the benchmark
concentration as the 95% lower confidence limit on the dose corresponding to a 10%
relative change in the endpoint compared to the control. Dose-effect data were
adjusted to account for discontinuous exposure (22 hr/day) and the maximum
likelihood model was used to fit continuous data to a polynomial mean response
regression, yielding maximum likelihood estimates of 0.036 - 0.078 mg/m3 and BMCs
of 0.016 - 0.067 mg/m3. Malsch et al. (1994) applied dosimetric adjustments and
uncertainty factors to determine a RfC based on the following equation:
RfC = BMC x RDDR
UFA x UFF x UFH
where:
RfC is the inhalation reference concentration
BMC is the benchmark concentration (lower 95% confidence limit on the
dose corresponding to a 10% relative change in the endpoint compared
to the control)
RDDR is the regional deposited dose ratio to account for pharmacokinetic
differences between species
UFA is a threefold uncertainty factor to account for pharmacodynamic
differences not addressed by the RDDR
UFF is a threefold uncertainty factor to account for extrapolating from
subchronic to chronic exposures; and
UFH is a 10-fold uncertainty factor to account for the variation in
sensitivity among members of the human population
The RDDR factor is incorporated to account for differences in the deposition
pattern of inhaled hexavalent chromium dusts in the respiratory tract of humans and
the Wistar rat test animals (Jarabek et al., 1990). The RDDR of 2.1576 was
determined based on the mass median aerodynamic diameter (0.28 µm for dose levels
of 0.05-0.1 mg/m3 and 0.39 for dose levels of 0.1-0.4 mg/m3) and the geometric
standard deviation (1.63 for dose levels of 0.05-0.1 mg/m3 and 1.72 for dose levels
of 0.1-0.4 mg/m3) of the particulates reported in Glaser et al. (1990).
A 3.16-fold uncertainty factor (midpoint between 1 and 10 on a log scale) was
incorporated to account for the pharmacodynamic differences not accounted for by
the RDDR. An additional 3.16-fold uncertainty factor was incorporated to account
for the less-than-lifetime exposure in Glaser et al. (1990), and a 10-fold
uncertainty factor was applied to account for variation in the human population. A
total uncertainty factor of 100 was applied to the BMC in addition to the RDDR.
Glaser et al. (1990) reported that LDH in BALF increased in a dose-dependent
fashion from 0.05 to 0.4 mg/m3 sodium dichromate, and this endpoint generated the
lowest BMC (0.016 mg/m3) and RfC (3.4 E-4 mg/m3). LDH in BALF is considered the
among the most sensitive indicators of potential lung toxicity (Henderson, 1984,
1985, 1988; Beck et al., 1982; Venet et al., 1985), as LDH is found extracellularly
after cell damage and BALF is the closest site to the original lung injury. LDH in
BALF may also reflect chronic lung inflammation, which may lead to pulmonary
fibrosis through prevention of the normal repair of lung tissue (Henderson, 1988).
Several uncertainties must be addressed with regard to the BMC and RfC
developed by Malsch et al. (1994). Potentially important endpoints, including
upper airway effects and potential renal or immunological toxicity, were not
addressed in the Glaser et al. (1985, 1990) studies and could not be included in
the BMC analysis. While LDH in BALF resulted in the lowest BMC and RfC, all of the
effects noted in Glaser et al. (1985, 1990) can be considered indicative of an
inflammatory response, and might be equally suited to development of the RfC. LDH
in BALF did not generate the best fit on the regression curve of the endpoints
considered in the BMC analysis. In addition, the threefold uncertainty factor
accounting for the use of a subchronic study may not be sufficiently protective for
long-term effects. While the analysis acknowledged the importance of particle size
and airway deposition in the development of the RDDR, the potential impact of
different particle sizes in respiratory toxicity by hexavalent chromium
particulates was not addressed.
Several of these uncertainties were conservatively addressed in the analysis
of Malsch et al. (1994). LDH in BALF generated the lowest estimate of the BMC from
the effects noted by Glaser et al. (1985, 1990). This effect can be considered to
be indicative of cell damage that occurs prior to fibrosis, as LDH appears in BALF
following cell lysis. While the Malsch et al. (1994) analysis demonstrated a
relatively poor curve fit for this endpoint, the model generated a conservative fit
in the data that is unlikely to overestimate the BMC. LDH in BALF as reported in
Glaser et al. (1990) is considered to be an acceptable endpoint for development of
an RfC for inhalation of hexavalent chromium particulates, and Malsch et al. (1994)
used a reasonable approach for development of a BMC based on this endpoint.
The threefold uncertainty factor used by Malsch et al. (1994) to account for
the subchronic study is insufficient for development of the RfC for inhalation of
chromium particulates. Glaser et al. (1985) demonstrated that at the end of the
90-day exposure period, chromium was still accumulating in the lung tissue of the
test animals, suggesting that lower long-term exposures might lead to accumulation
of a critical concentration in the lung. Subchronic studies also may not
adequately predict the presence of inflammatory effects from lower long-term
exposures. The Agency has therefore determined that a 10-fold uncertainty factor
accounting for the use of a subchronic study is more appropriate in this case for
the development of an RfC for inhalation of chromium particulates.
Selection of a threefold uncertainty factor to account for the pharmacodynamic
differences not accounted for by the RDDR, an additional 10-fold uncertainty factor
to account for the less-than-lifetime exposure in Glaser et al. (1990), and a
10-fold uncertainty factor to account for variation in the human population
generates a total uncertainty factor of 300. Application of the total uncertainty
factor of 300 and the RDDR of 2.1576 to the BMC generated by Malsch et al. (1994)
based on LDH in BALF (Glaser et al., 1990) results in an RfC of 1 E-4 mg/m3 for
inhalation of hexavalent chromium particulates.
___I.B.3. UNCERTAINTY AND MODIFYING FACTORS (INHALATION RfC)
See discussion above.
(1) Chromic acid mists and dissolved Cr (VI) aerosols:
UF = 90.
MF = 1.
(2) Chromium (VI) particulates:
UF = 300.
MF = 1
___I.B.4. ADDITIONAL STUDIES/COMMENTS (INHALATION RfC)
There is considerable uncertainty with regard to the relevance of the nasal
septum atrophy endpoint observed in the chromeplating industry to exposure to
hexavalent chromium in the environment. The effects were observed in chromeplaters
who were exposed to chromic acid mists near the plating baths. Environmental
exposures would most likely occur through contact with hexavalent chromium dusts,
and exposures to chromic acid mists in the environment is considered to be
unlikely. An additional uncertainty is related to the determination of dose in the
Lindberg and Hedenstierna study. Nasal septum atrophy in this study was related to
TWA exposures to chromic acid. The most significant effects (nasal septum
perforation) were observed in workers who experienced peak excursions to levels
considerably greater than the TWA. It is uncertain whether the peak excursion data
or the TWAs are more appropriate for the determination of dose in this study. The
RfC based on the data of Lindberg and Hedenstierna (1983) should only be used to
address exposures to chromic acid and dissolved hexavalent chromium aerosols.
Nasal mucosal irritation, atrophy, and perforation have been widely reported
following occupational exposures to chromic acid mists and dissolved hexavalent
chromium aerosols. Glaser et al. (1990) did not report on upper respiratory
effects following exposure of rats to sodium dichromate. The RfC based on the data
of Glaser et al. should only be used to address inhalation of Cr(VI) particulates.
The RfCs in this IRIS Summary were added in 1998. The previous RfC section
for hexavalent chromium in IRIS was empty.
___I.B.5. CONFIDENCE IN THE INHALATION RfC
(1) Chromic acid mists and dissolved Cr (VI) aerosols:
Study -- Low
Database -- Low
RfC -- Low
The overall confidence in this RfC assessment is low. Confidence in the
chosen study is low because of uncertainties regarding the exposure
characterization and the role of direct contact for the critical effect. Confidence
in the database is low because the supporting studies are equally uncertain
regarding the exposure characterization.
(2) Chromium (VI) particulates:
Study -- Medium
RfC -- Medium
The overall confidence in this RfC assessment is medium. Confidence in the
chosen study is medium because of uncertainties regarding upper respiratory,
reproductive, and renal effects resulting from the exposures.
___I.B.6. EPA DOCUMENTATION AND REVIEW OF THE INHALATION RfC
Source Document -- U.S. EPA, 1998
This assessment was peer reviewed by external scientists. Their comments have
been evaluated carefully and incorporated in finalization of this IRIS summary. A
record of these comments is included as an appendix to the Toxicological Review of
Hexavalent Chromium in support of Summary Information on the Integrated Risk
Information System (IRIS) (U.S. EPA, 1998).
Agency Consensus Date -- 04/28/1998
___I.B.7. EPA CONTACTS (INHALATION RfC)
Please contact the Risk Information Hotline for all questions concerning this
assessment or IRIS, in general, at (513) 569-7254 (phone), (513) 569-7159 (fax), or
RIH.IRIS@EPAMAIL.EPA.GOV (Internet address).
_II. CARCINOGENICITY ASSESSMENT FOR LIFETIME EXPOSURE
Substance Name: Chromium(VI)
CASRN: 18540-29-9
Last Revised -- 09/03/1998
Section II provides information on three aspects of the carcinogenic
assessment for the substance in question; the weight-of-evidence judgment of the
likelihood that the substance is a human carcinogen, and quantitative estimates of
risk from oral exposure and from inhalation exposure. The quantitative risk
estimates are presented in three ways. The slope factor is the result of
application of a low-dose extrapolation procedure and is presented as the risk per
(mg/kg)/day. The unit risk is the quantitative estimate in terms of either risk
per µg/L drinking water or risk per µg/m3 air breathed. The third form in which
risk is presented is a concentration of the chemical in drinking water or air
associated with cancer risks of 1 in 10,000, 1 in 100,000, or 1 in 1,000,000. The
rationale and methods used to develop the carcinogenicity information in IRIS are
described in The Risk Assessment Guidelines of 1986 (EPA/600/8-87/045) and in the
IRIS Background Document. IRIS summaries developed since the publication of EPA's
more recent Proposed Guidelines for Carcinogen Risk Assessment also utilize those
Guidelines where indicated (Federal Register 61(79):17960-18011, April 23, 1996).
Users are referred to Section I of this IRIS file for information on long-term
toxic effects other than carcinogenicity.
__II.A. EVIDENCE FOR HUMAN CARCINOGENICITY
___II.A.1. WEIGHT-OF-EVIDENCE CHARACTERIZATION
Under the current guidelines (EPA, 1986), Cr(VI) is classified as Group A -
known human carcinogen by the inhalation route of exposure. Carcinogenicity by the
oral route of exposure cannot be determined and is classified as Group D.
Under the proposed guidelines (EPA, 1996), Cr(VI) would be characterized as a
known human carcinogen by the inhalation route of exposure on the following basis.
Hexavalent chromium is known to be carcinogenic in humans by the inhalation
route of exposure. Results of occupational epidemiologic studies of
chromium-exposed workers are consistent across investigators and study populations.
Dose-response relationships have been established for chromium exposure and lung
cancer. Chromium-exposed workers are exposed to both Cr(III) and Cr(VI) compounds.
Because only Cr(VI) has been found to be carcinogenic in animal studies, however,
it was concluded that only Cr(VI) should be classified as a human carcinogen.
Animal data are consistent with the human carcinogenicity data on hexavalent
chromium. Hexavalent chromium compounds are carcinogenic in animal bioassays,
producing the following tumor types: intramuscular injection site tumors in rats
and mice, intrapleural implant site tumors for various Cr(VI) compounds in rats,
intrabronchial implantation site tumors for various Cr(VI) compounds in rats, and
subcutaneous injection site sarcomas in rats.
In vitro data are suggestive of a potential mode of action for hexavalent
chromium carcinogenesis. Hexavalent chromium carcinogenesis may result from the
formation of mutagenic oxidatitive DNA lesions following intracellular reduction to
the trivalent form. Cr(VI) readily passes through cell membranes and is rapidly
reduced intracellularly to generate reactive Cr(V) and Cr(IV) intermediates and
reactive oxygen species. A number of potentially mutagenic DNA lesions are formed
during the reduction of Cr(VI). Hexavalent chromium is mutagenic in bacterial
assays, yeasts, and V79 cells, and Cr(VI) compounds decrease the fidelity of DNA
synthesis in vitro and produce unscheduled DNA synthesis as a consequence of DNA
damage. Chromate has been shown to transform both primary cells and cell lines.
___II.A.2. HUMAN CARCINOGENICITY DATA
Occupational exposure to chromium compounds has been studied in the chromate
production, chromeplating and chrome pigment, ferrochromium production, gold
mining, leather tanning, and chrome alloy production industries.
Workers in the chromate industry are exposed to both trivalent and hexavalent
compounds of chromium. Epidemiological studies of chromate production plants in
Japan, Great Britain, West Germany, and the United States have revealed a
correlation between occupational exposure to chromium and lung cancer, but the
specific form of chromium responsible for the induction of cancer was not
identified (Machle and Gregorius, 1948; Baejter, 1950a,b; Bidstrup, 1951;
Mancuso and Hueper, 1951; Brinton et al., 1952; Bidstrup and Case, 1956; Todd,
1962; Taylor, 1966; Enterline, 1974; Mancuso, 1975; Ohsaki et al., 1978; Sano and
Mitohara, 1978; Hayes et al., 1979; Hill and Ferguson, 1979; Alderson et al., 1981;
Haguenor et al., 1981; Satoh et al., 1981; Korallus et al., 1982; Frentzel-Beyme,
1983; Langard and Vigander, 1983; Watanabe and Fukuchi, 1984; Davies, 1984;
Mancuso, 1997).
Mancuso and Hueper (1951) conducted a proportional mortality study of a cohort
of chromate workers (employed for > l year from 1931-1949 in a Painesville, OH
chromate plant) in order to investigate lung cancer associated with chromate
production. Of the 2,931 deaths of males in the county where the plant is 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. Within the limitations
of the study design, this report strongly suggested an increased incidence of
respiratory cancer in the chromate-production plant.
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. Lung cancer death rates increased by gradient of exposure to total
chromium, and significant deposition of chromium was found in the lungs of workers
long after the exposure ceased. Mancuso (1975) reported that these lung cancer
deaths were related to insoluble (trivalent), soluble (hexavalent), and total
chromium exposure, but the small numbers involved make identification of the
specific form of chromium responsible for the lung cancer uncertain.
Mancuso (1997) recently updated this study, following the combined cohort of
332 workers until 1993. Of 283 deaths (85% of the cohort identified), 66 lung
cancers were found (23.3% of all deaths and 64.7% of all cancers). Lung cancer
rates clearly increased by gradient level of exposure to total chromium. The
relationship between gradient level of exposure and lung cancer rates is less clear
for trivalent and hexavalent chromium. The rates of lung cancer within the cohort
are consistent with those reported in Mancuso (1975), and provide further support
for the cancer risk assessment based on those data.
Studies of chrome pigment workers in the United States (Hayes et al., 1989),
England (Davies, 1984, 1979, 1978), Norway (Langard and Vigander, 1983; Langard and
Norseth, 1975), and in the Netherlands and Germany (Frentzel-Beyme, 1983) have
consistently demonstrated an association between occupational chromium exposure
(predominantly to Cr [VI]) and lung cancer.
Several studies of the chromeplating industry have demonstrated a positive
relationship between cancer and exposure to chromium compounds (Royle, 1975;
Franchini et al., 1983; Sorahan et al., 1987).
___II.A.3. ANIMAL CARCINOGENICITY DATA
Animal data are consistent with the findings of human epidemiological studies
of hexavalent chromium. Hexavalent chromium compounds were carcinogenic in animal
assays producing the following tumor types: lung tumors following inhalation of
aerosols of sodium chromate and pyrolized Cr(VI)/Cr(III) oxide mixtures in rats
(Glaser et al., 1986), lung tumors following intratracheal administration of sodium
dichromate in rats (Steinhoff et al., 1983), intramuscular injection site tumors in
Fischer 344 and Bethesda Black rats and in C57BL mice (Furst et al., 1976; Maltoni,
1974, 1976; Payne, 1960a; Hueper and Payne, 1959); intrapleural implant site
tumors for various Cr(VI) compounds in Sprague-Dawley and Bethesda Black rats
(Payne, 1960b; Hueper 1961; Hueper and Payne, 1962), intrabronchial implantation
site tumors for various Cr(VI) compounds in Wistar rats (Levy and Martin, 1983;
Laskin et al., 1970; Levy, as quoted in NIOSH, 1975), and subcutaneous injection
site sarcomas in Sprague-Dawley rats (Maltoni, 1974, 1976). Inflammation is
considered to be essential for the induction of most chromium respiratory effects
and may influence the carcinogenicity of Cr(VI) compounds (Glaser et al., 1985).
___II.A.4. SUPPORTING DATA FOR CARCINOGENICITY
Metabolism and genotoxicity. Hexavalent chromium is rapidly taken up by cells
through the sulfate transport system (Sugiyama, 1992). Once inside the cell,
Cr(VI) is quickly reduced to the trivalent form by cellular reductants, including
ascorbic acid, glutathione and flavoenzymes (cytochrome P-450 and glutathione
reductase), and riboflavin (De Flora et al., 1989; De Flora et al., 1990; Sugiyama,
1992). The intracellular reduction of Cr(VI) generates reactive Cr(V) and
Cr(IV) intermediates as well as hydroxyl free radicals (OH) and singlet oxygen
(1O2) (Kawanishi et al., 1986). A variety of DNA lesions are formed during the
reduction of Cr(VI) to Cr(III), including DNA strand breaks, alkali-labile sites,
DNA-protein and DNA-DNA crossLINKS, and oxidative DNA damage, such as
8-oxo-deoxyguanosine (Klein et al., 1992; Klein et al., 1991; De Flora et al.,
1990). The relative importance of the different chromium complexes and oxidative
DNA damage in the toxicity of Cr(VI) is unknown.
A large number of chromium compounds have been assayed with in vitro genetic
toxicology assays. In general, hexavalent chromium is mutagenic in bacterial
assays whereas trivalent chromium is not (Lofroth, 1978; Petrilli and DeFlora,
1977, 1978). Likewise Cr(VI), but not Cr(III), was mutagenic in yeasts (Bonatti et
al., 1976) and in V79 cells (Newbold et al., 1979). Cr(III) and (VI) compounds
decrease the fidelity of DNA synthesis in vitro (Loeb et al., 1977), while Cr(VI)
compounds inhibit replicative DNA synthesis in mammalian cells (Levis et al., 1978)
and produce unscheduled DNA synthesis, presumably repair synthesis, as a
consequence of DNA damage (Raffetto, 1977). Chromate has been shown to transform
both primary cells and cell lines (Fradkin et al., 1975; Tsuda and Kato, 1977;
Casto et al., 1979). Chromosomal effects produced by treatment with chromium
compounds have been reported by a number of authors; for example, both Cr(VI) and
Cr(III) salts were clastogenic for cultured human leukocytes (Nakamuro et al.,
1978).
In dogs (2/group) exposed to potassium dichromate in drinking water at
concentrations up to 11.2 ppm for 4 years, gross and microscopic examination of all
major organs revealed no treatment-related lesions (Anwar et al., 1961). The small
number of animals and the relatively short exposure duration relative to the
lifespan of the dog precludes a conclusion regarding a possible carcinogenic
response. There are no other long-term studies of ingested Cr(VI). Cr(VI)
is readily converted to Cr(III) in vivo, but there is no evidence that Cr(III) is
oxidized to Cr(VI) in vivo. Cr(III) is an essential trace element.
__II.B. QUANTITATIVE ESTIMATE OF CARCINOGENIC RISK FROM ORAL EXPOSURE
The oral carcinogenicity of Cr(VI) cannot be determined. No data were located
in the available literature that suggested that Cr(VI) is carcinogenic by the oral
route of exposure.
__II.C. QUANTITATIVE ESTIMATE OF CARCINOGENIC RISK FROM INHALATION
EXPOSURE
___II.C.1. SUMMARY OF RISK ESTIMATES
____II.C.1.1. Air Unit Risk -- 1.2E-2 (µg/m3)
Source: Mancuso, 1975
____II.C.1.2. Extrapolation Method -- Multistage, extra risk
Air Concentrations at Specified Risk Levels:
Risk Level Concentration
E-4 (1 in 10,000) 8E-3 (µg/m3)
E-5 (1 in 100,000) 8E-4 (µg/m3)
E-6 (1 in 1,000,000) 8E-5 (µg/m3)
___II.C.2. DOSE-RESPONSE DATA FOR CARCINOGENICITY, INHALATION
EXPOSURE
Tumor type -- lung cancer
Test animals -- human
Route -- inhalation, occupational exposure
Source -- Mancuso, 1975
Exposure level Deaths from
Subject age (years) midrange (µg/m3) lung cancer Person-years
50 5.66 3 1,345
25.27 6 931
46.83 6 299
60 4.68 4 1,063
20.79 5 712
39.08 5 211
70 4.41 2 401
21.29 4 345
___II.C.3. ADDITIONAL COMMENTS (CARCINOGENICITY, INHALATION EXPOSURE)
Mancuso (1997) recently updated the study of Mancuso (1975), following the
combined cohort of 332 workers until 1993. Of 283 deaths (85% of the cohort
identified), 66 lung cancers were found (23.3% of all deaths and 64.7% of all
cancers). Lung cancer rates clearly increased by gradient level of exposure to
total chromium. The relationship between gradient level of exposure and lung
cancer rates is less clear for trivalent and hexavalent chromium. The rates of
lung cancer within the cohort are consistent with those reported in Mancuso (1975),
and provide further support for the cancer risk assessment based on those data.
The cancer mortality in Mancuso (1975) was assumed to be due to Cr(VI), which
was further assumed to be no less than one-seventh of total chromium. It was also
assumed that the smoking habits of chromate workers were similar to those of the
U.S. white male population.
Trivalent chromium compounds have not been reported as carcinogenic by any
route of administration.
The unit risk should not be used if the air concentration exceeds 8E-1 µg/m3,
since above this concentration the unit risk may not be appropriate.
The carcinogenicity section of this IRIS Summary was updated in 1998; however,
the quantitative results have not been modified.
___II.C.4. DISCUSSION OF CONFIDENCE (CARCINOGENICITY, INHALATION
EXPOSURE)
Results of studies of chromium exposure are consistent across investigators
and countries. A dose relationship for lung tumors has been established. The
assumption that the ratio of Cr(III) to Cr(VI) is 6:1 may lead to a sevenfold
underestimation of risk. The use of 1949 hygiene data (Bourne and Yee, 1950),
which may underestimate worker exposure, may result in an overestimation of risk.
Further overestimation of risk may be due to the implicit assumption that the
smoking habits of chromate workers were similar to those of the general white male
population, since it is generally accepted that the proportion of smokers is higher
for industrial workers than for the general population.
__II.D. EPA DOCUMENTATION, REVIEW, AND CONTACTS (CARCINOGENICITY
ASSESSMENT)
___II.D.1. EPA DOCUMENTATION
Source Document -- U.S. EPA, 1998
This assessment was peer reviewed by external scientists. Their comments have
been evaluated carefully and incorporated in finalization of this IRIS summary. A
record of these comments is included as an appendix to U.S. EPA, 1998.
Other EPA Documentation -- U.S. EPA. (1984) Health assessment document for
chromium. Prepared by the Office of Health and Environmental Assessment,
Environmental Criteria and Assessment Office, Cincinnati, OH. EPA/600/8-83-014F.
___II.D.2. EPA REVIEW (CARCINOGENICITY ASSESSMENT)
Agency consensus date -- 04/28/1998
___II.D.3. EPA CONTACTS (CARCINOGENICITY ASSESSMENT)
Please contact the Risk Information Hotline for all questions concerning this
assessment or IRIS, in general, at (513) 569-7254 (phone), (513) 569-7159 (fax), or
RIH.IRIS@EPAMAIL.EPA.GOV (Internet address).
_III. [reserved]
_IV. [reserved]
_V. [reserved]
_VI. BIBLIOGRAPHY
Chromium(VI)
CASRN -- 18540-29-9
Last Revised -- 09/03/1998
__VI.A. ORAL RfD REFERENCES
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__VI.B. INHALATION RfC REFERENCES
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__VI.C. CARCINOGENICITY ASSESSMENT REFERENCES
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_VII. REVISION HISTORY
Chromium(VI)
CASRN --18540-29-9
Date Section Description
09/30/1987 II.A.1. Citation corrected
03/01/1988 II.C.4. Confidence statement revised
03/01/1988 II.D.3. Contacts switched
03/01/1988 III.A. Health Advisory added
12/01/1989 I.B. Inhalation RfD now under review
06/01/1990 II.A.1. Basis - Text revised
06/01/1990 II.B. Text revised
06/01/1990 IV.A.1. Area code for EPA contact corrected
06/01/1990 IV.F.1. EPA contact changed
06/01/1990 VI. Bibliography on-line
01/01/1991 II. Text edited
01/01/1991 II.C.1. Inhalation slope factor removed (global change)
03/01/1991 II.A.1. Text revised
03/01/1991 II.A.4. Text revised
03/01/1991 II.B. Text revised
01/01/1992 I.A.7. Secondary contact changed
01/01/1992 IV. Regulatory actions updated
04/01/1992 IV.A.1. CAA regulatory action withdrawn
06/01/1992 All CASRN corrected from 7440-47-3 to 18540-29-9
09/01/1994 I.A.6. Work group review date added
02/01/1995 I.A. RfD noted as pending change: Work Grp
Mtg on 08/03/1994
12/01/1996 I.A.7. Secondary contact removed
09/03/1998 I,II,VI Revised RfD, RfC, carcinogenicity assessment,
refs.
_VIII. SYNONYMS
Chromium(VI)
CASRN --18540-29-9
Last Revised -- 03/31/1987
18540-29-9
7440-47-3
Chromic ion
Chromium
Chromium, ion
Chromium (VI)
Chromium (VI) ion
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