List of IRIS Substances 

Search IRIS by Keyword

IRIS Summaries/Toxicological 

Reviews

Entire IRIS Website

Category (section) Status Last Revised

You are here: EPA Home Research Environmental Assessment IRIS IRIS Summaries

view QuickView 

Reference Dose for Chronic Oral Exposure (RfD) 

You will need Adobe Reader to view some of the files on this page. See EPA's PDF 

page to learn more.

Note: A TOXICOLOGICAL REVIEW is available for this chemical in Adobe PDF Format (70 Pages,189 

Kbytes). Similar documents can be found in the List of Available IRIS Toxicological Reviews. 

Links to specific pages in the toxicological review are available throughout this summary. To 

utilize this feature, your Web browser and Adobe program must be configured properly so the PDF displays 

within the browser window. If your browser and Adobe program need configuration, please go to EPA's 

PDF page for instructions.

[UPDATE] This assessment is currently under development and the latest draft can be found at, IRIS 

Toxicological Review of Hexavalent Chromium (External Review Draft)

0144 

Chromium (VI) ; CASRN 18540-29-9; 09/03/1998

Human health assessment information on a chemical substance is included in the IRIS database 

only after a comprehensive review of toxicity data, as outlined in the IRIS assessment 

development process. Sections I (Health Hazard Assessments for Noncarcinogenic Effects) and II 

(Carcinogenicity Assessment for Lifetime Exposure) present the conclusions that were reached 

during the assessment development process. Supporting information and explanations of the 

methods used to derive the values given in IRIS are provided in the guidance documents located 

on the IRIS website. 

STATUS OF DATA FOR Chromium (VI)

File First On-Line 03/31/1987

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 

Integrated Risk Information System

http://www.epa.gov/iris/subst/0144.htm

Last updated on Thursday, August 09, 2012

http://www.epa.gov/iris/subst/0144.htm
Critical Effect Experimental Doses*

_I. Chronic Health Hazard Assessments for Noncarcinogenic Effects

_I.A. Reference Dose for Chronic Oral Exposure (RfD)

Substance Name — 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

UF MF RfD

None Reported

Rat, 1-year drinking 

water study

MacKenzie et al., 1958 

NOAEL: 25 mg/L of chromium

as K2CrO4

2.5 mg/kg-day (adj.)

LOAEL: None 

300 3 3E-3 

mg/kg-day

*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 

http://www.epa.gov/iris/subst/0144.htm
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 

http://www.epa.gov/iris/subst/0144.htm
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 dosedependent 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 dosedependent 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 

http://www.epa.gov/iris/subst/0144.htm
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.

For more detail on other Hazard Identification Issues, exit to the toxicological review, 

Section 4.7 (PDF).

__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. 

For more detail on Characterization of Hazard and Dose Response, exit to the 

toxicological review, Section 6 (PDF).

__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 Acetonitrile in Support of Summary 

Information (a PDF document) on the Integrated Risk Information System (IRIS) (U.S. EPA, 

1998). To review this appendix, exit to the toxicological review, Appendix A, External 

Peer Review -- Summary of Comments and Disposition (PDF).

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

http://www.epa.gov/iris/subst/0144.htm
Screening-Level Literature Review Findings — A screening-level review conducted by an EPA 

contractor of the more recent toxicology literature pertinent to the RfD for Chromium (VI) 

conducted in August 2003 did not identify any critical new studies. IRIS users who know of 

important new studies may provide that information to the IRIS Hotline at hotline.iris@epa.gov or 

202-566-1676.

__I.A.7. EPA Contacts (Oral RfD)

Please contact the IRIS Hotline for all questions concerning this assessment or IRIS, in general, 

at (202)566-1676 (phone), (202)566-1749 (fax), or hotline.iris@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

Human subchronic

occupational study

Lindberg and

Hedenstierna, 1983 

NOAEL: none

LOAEL: 2E-3 mg/m3

7.14 E-4 mg/m3 (adj.) 

90 1 8E-6

mg/m3

(2) Cr(VI) particulates:

Lactate dehydrogenase

in bronchioalveolar

lavage fluid

Rat subchronic study

Glaser et al., 1990 

Malsch et al., 1994 

BMD: 0.016 mg/m3

0.034 mg/m3 (adj.) 

300 1 1E-4 

mg/m3

http://www.epa.gov/iris/subst/0144.htm
*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 functionmeasurements. 

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.

http://www.epa.gov/iris/subst/0144.htm
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 

http://www.epa.gov/iris/subst/0144.htm
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:

http://www.epa.gov/iris/subst/0144.htm
• RfC is the inhalation reference concentration

• BMC is the benchmark concentration (lower 95% confidence limit on thedose 

corresponding to a 10% relative change in the endpoint compared to the control)

• RDDR is the regional deposited dose ratio to account for pharmacokineticdifferences 

between species

• UFA is a threefold uncertainty factor to account for pharmacodynamicdifferences 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 

http://www.epa.gov/iris/subst/0144.htm
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-thanlifetime 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 

http://www.epa.gov/iris/subst/0144.htm
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.

For more detail on other Hazard Identification Issues, exit to the toxicological review, 

Section 4.7 (PDF).

__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. 

For more detail on Characterization of Hazard and Dose Response, exit to the 

toxicological review, Section 6 (PDF).

__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 Acetonitrile in Support of Summary 

Information (a PDF document) on the Integrated Risk Information System (IRIS) (U.S. EPA, 

1998). To review this appendix, exit to the toxicological review, Appendix A, External 

Peer Review -- Summary of Comments and Disposition (PDF).

Agency Consensus Date — 04/28/1998

Screening-Level Literature Review Findings — A screening-level review conducted by an EPA 

contractor of the more recent toxicology literature pertinent to the RfC for Chromium (VI) 

conducted in August 2003 did not identify any critical new studies. IRIS users who know of 

http://www.epa.gov/iris/subst/0144.htm
important new studies may provide that information to the IRIS Hotline at hotline.iris@epa.gov or 

202-566-1676.

__I.B.7. EPA Contacts (Inhalation RfC)

Please contact the IRIS Hotline for all questions concerning this assessment or IRIS, in general, 

at (202)566-1676 (phone), (202)566-1749 (fax), or hotline.iris@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 

http://www.epa.gov/iris/subst/0144.htm
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. 

For more detail on Characterization of Hazard and Dose Response, exit to the 

toxicological review, Section 6 (PDF). 

For more detail on other Hazard Identification Issues, exit to the toxicological review, 

Section 4.7 (PDF). 

__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.

http://www.epa.gov/iris/subst/0144.htm
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 (1

O2) (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 

http://www.epa.gov/iris/subst/0144.htm
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 per (μg/cu.m) 

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

http://www.epa.gov/iris/subst/0144.htm
Subject age (years)

Exposure Level

midrange (μg/m3) Deaths From Lung Cancer Person-Years

50 5.66

25.27

46.83

3

6

6

1,345

931

299

60 4.68

20.79

39.08

4

5

5

1,063

712

211

70 4.41

21.29

2

4

401

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. Theassumption 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

http://www.epa.gov/iris/subst/0144.htm
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 Acetonitrile in Support of Summary 

Information (a PDF document) on the Integrated Risk Information System (IRIS) (U.S. EPA, 

1998). To review this appendix, exit to the toxicological review, Appendix A, External 

Peer Review -- Summary of Comments and Disposition (PDF). 

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

Screening-Level Literature Review Findings — A screening-level review conducted by an EPA 

contractor of the more recent toxicology literature pertinent to the cancer assessment for 

Chromium (VI) conducted in August 2003 did not identify any critical new studies. IRIS users who 

know of important new studies may provide that information to the IRIS Hotline at 

hotline.iris@epa.gov or 202-566-1676.

__II.D.3. EPA Contacts (Carcinogenicity Assessment)

Please contact the IRIS Hotline for all questions concerning this assessment or IRIS, in general, 

at (202)566-1676 (phone), (202)566-1749 (fax), or hotline.iris@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

Anwar, RA; Langham, FF; Hoppert, CA; et al. (1961) Chronic toxicity studies. III. Chronic toxicity 

of cadmium and chromium in dogs. Arch Environ 3:456-460.

Bruynzeel, DP; Hennipman, G; van Ketel, WG. (1988) Irritant contact dermatitis and chromiumpassivated metal. Contact Derm 19:175-179.

Burrows, D; Adams, RM. (1990) In: Occupational skin disease, 2nd ed., Adams, RM, d. 

Philadelphia: W.B. Saunders, pp. 349-386.

Cronin, E. (1980) Contact dermatitis. New York: Churchill Livingstone, pp. 287-390.

http://www.epa.gov/iris/subst/0144.htm
Elbetieha, A; Al-Hamood, MH. (1997) Long-term exposure of male and female mice to trivalent 

and hexavalent chromium compounds: effect on fertility. Toxicology 116:19-47.

Fregert, S. (1981) Chromium valencies and cement dermatitis. Br J Dermatol 105 (suppl. 

21):7-9.

Gruber, JE; Jennette, KW. (1978) Metabolism of the carcinogen chromate by rat liver

microsomes. Biochem Biophys Res Commun 82(2):700-706.

Hunter, D. (1974) The diseases of occupations, 5th ed. Boston: Little, Brown.

Junaid, M; Murthy, RC; Saxena, DK. (1996) Embryotoxicity of orally administered chromium in 

mice: exposure during the period of organogenesis. Toxicol Lett 84:143-148.

Kanojia, RK; Junaid, M; Murthy, RC. (1996) Chromium induced teratogenicity in female rat. 

Toxicol Lett 89:207-213.

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.

National Toxicology Program (NTP). (1996a) Final Report. Potassium dichromate (hexavalent): 

The effects of potassium dichromate on Sprague-Dawley rats when administered in the diet. 

December 13, 1996.

National Toxicology Program (NTP). (1996b) Final Report. Potassium dichromate (hexavalent): 

The effects of potassium dichromate in BALB/c mice when administered in the diet. November 27, 

1996.

National Toxicology Program (NTP). (1997) Final Report. Potassium dichromate (hexavalent): 

Reproductive assessment by continuous breeding when administered to BALB/c mice in the diet. 

February 18, 1997.

Petrilli, FL; DeFlora, S. (1977) Toxicity and mutagencity of hexavalent chromium on Salmonella 

typhimurium. Appl Environ Microbiol 33(4):805-809.

Petrilli, FL; DeFlora, S. (1978) Oxidation of inactive trivalent chromium to the mutagenic 

hexavalent form. Mutat Res 58(2-3):167-178.

Polak, L. (1983) Immunology of chromium. In: Chromium: metabolism and toxicity. Burrows, D, 

ed. Boca Raton, FL: CRC Press, pp. 51-135.

Polak, L; Turk, JL; Frey, FR. (1973) Studies on contact hypersensitivity to chromium compounds. 

Progr Allergy 17:145-219.

Spruit, D; van Neer, FCJ. (1966) Penetration rate of Cr(III) and Cr(VI). Dermatological 132:179-

182.

U.S. Environmental Protection Agency (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 

http://www.epa.gov/iris/subst/0144.htm
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.

U.S. EPA. (1998) Toxicological review of hexavalent chromium. Available online at 

http://www.epa.gov/iris.

Zhang, J; Li, X. (1987) Chromium pollution of soil and water in Jinzhou. J of Chinese Preventive 

Med 21:262-264.

_VI.B. Inhalation RfC References

Beck, BD; Brain, JD; Bohannon, DE. (1982) An in vivo hamster bioassay to assess the toxicity of 

particles for the lungs. Toxicol Appl Pharmacol 66:9-29.

Cohen, SR; Davis, DM; Kramkowski, RS. (1974) Clinical manifestations of chronic acid toxicity--

Nasal lesions in electroplate workers. Cutis 13:558-568. 

Glaser, U; Hochrainer, D; Kloppe, H; et al. (1985) Low level chromium (VI) inhalation effects on 

alveolar macrophages and immune function in Wistar rats. Arch Toxicol 57(4):250-256.

Glaser, U; Hochrainer, D; Steinhoff, D. (1990) Investigation of irritating properties of inhaled Cr

(VI) with possible influence on its carcinogenic action. In: Environmental Hygiene II. Seemayer, 

NO; Hadnagy, W, eds. Berlin/New York: Springer-Verlag.

Henderson, RF. (1984) Use of bronchoalveolar lavage to detect lung damage. Environ Health 

Perspect 56:115-129.

Henderson, RF. (1988) Use of bronchoalveolar lavage to detect lung damage. In: Toxicology of 

the lung. Gardner, DE; Crapo, JD; Masaro, EJ, eds., New York: Raven Press.

Henderson, RF; Benson, JM; Hahn, FF. (1985) New approaches for the evaluation of pulmonary 

toxicity: bronchoalveolar lavage fluid analysis. Fundam Appl Toxicol 5:451-458.

Lees, PSJ; Gibb, HJ; Rooney, BC. (1995) Derivation of exposure-response relationship for 

chromium from historic exposure data. 11th International Symposium of Epidemiology in 

Occupational Health, the Netherlands, September 1995.

Lindberg, E; Hedensteirna, G. (1983) Chrome plating: Symptoms, finding in the upper airways 

and effects on lung function. Arch Environ Health 38:367-374.

Lucas, JB; Kramkowski, RS. (1975) Health Hazard Evaluation Report No. 74-87-221. Cincinnati, 

OH. Health Hazard Evaluation Branch, U.S. Department of Health, Education, and Welfare, Public 

Health Service, Center for Disease Control. National Institute for Occupational Safety and Health.

Malsch, PA; Proctor, DM; Finley, BL. (1994) Estimation of a chromium inhalation reference 

concentration using the benchmark dose method: a case study. Regul Toxicol Pharmacol 20:58-

82.

http://www.epa.gov/iris/subst/0144.htm
U.S. EPA. (1998) Toxicological review of hexavalent chromium. Available online at 

http://www.epa.gov/iris.

Venet, A; Clavel, F; Israel-Biet, D; et al. (1985) Lung in acquired immune deficiency syndrome: 

Infectious and immunological status assessed by bronchioalveolar lavage. Bull Eur Physiopathol 

Respir 21:535-543.

_VI.C. Carcinogenicity Assessment References

Alderson, MR; Rattan, NS; Bidstrup, L. (1981) Health of workmen in the chromate-producing 

industry in Britain. Br J Ind Med 38:117-124.

Baetjer, AM. (1950a) Pulmonary carcinoma in chromate workers. In: A review of the literature 

and report of cases. Arch Ind Hyg Occup Med 2(5):487-504.

Baetjer, AM. (1950b) Pulmonary carcinoma in chromate workers. II. Incidence on basis of 

hospital records. Arch Ind Hyg Occup Med 2(5):505-516.

Bidstrup, PL. (1951) Carcinoma of the lung in chromate workers. Br J Med 8:302-305.

Bidstrup, PL; Case, RAM. (1956) Carcinoma of the lung in workmen in the bichromates-producing 

industry in Great Britain. Br J Ind Med 13:260-264.

Bonatti, S; Meini, M; Abbondandolo, A. (1976) Genetic effects of potassium dichromate in 

Schizosaccharomyces pombe. Mutat Res 38:147-150.

Bourne, HG, Jr; Yee, HT. (1950) Occupational cancer in a chromate plant - an environmental 

appraisal. Ind Med Surg 19(12):563-567.

Brinton, HP; Frasier, ES; Koven AL. (1952) Morbidity and mortality experience among chromate 

workers. Public Health Rep 67(9):835-847.

Casto, BC; Meyers, J; DiPaolo, JA. (1979) Enhancement of viral transformation for evaluation of 

the carcinogenic or mutagenic potential of inorganic metal salts. Cancer Res 39:193-198.

Davies, JM. (1978) Lung-cancer mortality in workers making chrome pigments. Lancet 1:384.

Davies, JM. (1979) Lung cancer mortality of workers in chromate pigment manufacture: An 

epidemiological survey. J Oil Chem Assoc 62:157-163. 

Davies, JM. (1984) Lung cancer mortality among workers making lead chromate and zinc 

chromate pigments at three English factories. Br J Ind Med 41:158-169.

De Flora, S; Wetterhahn, KE. (1989) Mechanisms of chromium metabolism and genotoxicity. Life 

Chem Rep 7:169-244.

De Flora, S; Bagnasco, M; Serra, D; et al. (1990) Genotoxicity of chromium compounds: a 

review. Mutat Res 238:99-172.

Enterline, PE. (1974) Respiratory cancer among chromate workers. J Occup Med 16:523-526.

http://www.epa.gov/iris/subst/0144.htm
Fradkin, A; Janoff, A; Lane, BP; et al. (1975) In vitro transformation of BHK21 cells grown in the 

presence of calcium chromate. Cancer Res 35:1058-1063.

Frentzel-Beyme, R. (1983) Lung cancer mortality of workers employed in chromate pigment 

factories. A multicentric European epidemiological study. J Cancer Res Clin Oncol 105:183-188.

Furst, A; Schlauder, M; Sasmore, DP. (1976) Tumorigenic activity of lead chromate. Cancer Res 

36:1779-1783.

Glaser, U; Hochrainer, D; Kloppel, H; et al. (1986) Carcinogenicity of sodium dichromate and 

chromium(VI/III) oxide aerosols inhaled by male Wistar rats. Toxicology 42:219-232.

Haguenor, JM; Dubois, G; Frimat, P; et al. (1981) Mortality due to bronch-pulmonary >cancer in 

a factory producing pigments based on lead and zinc chromates. In: Prevention of occupational 

cancer - International symposium, occupational safety and health series 46. Geneva, Switzerland: 

International Labour Office, pp. 168-176. (French).

Hayes, RB; Lilienfeld, AM; Snell, LM. (1979) Mortality in chromium chemical production workers: 

a prospective study. Int J Epidemiol 8(4):365-374.

Hayes, RB; Sheffet, A; Spirtas, R. (1989) Cancer mortality among a cohort of chromium pigment 

workers. Am J Ind Med 16:127-133.

Hill, WJ; Ferguson, WS. (1979) Statistical analysis of epidemiological data from chromium 

chemical manufacturing plant. J Occup Med 21:103-106. 

Hueper, WC. (1961) Environmental carcinogenesis and cancers. Cancer Res 21:842-857.

Hueper, WC; Payne, WW. (1962) Experimental studies in metal carcinogenesis: Chromium, 

nickel, iron, and arsenic. Arch Environ Health 5:445-462.

Hill, WJ; Ferguson, WS. (1979) Statistical analysis of epidemiological data from a chromium 

chemical manufacturing plant. J Occup Med 21(2):103-106.

Kawanishi, S; Inoue, S; Sano, S. (1986) Mechanism of DNA cleavage induced by sodium 

chromate (VI) in the presence of hydrogen peroxide. J Biol Chem 261:5952-5958.

Klein, CB; Frenkel, K; Costa, M. (1992) Chromium mutagenesis in transgenic gpt+ Chinese 

hamster cell lines. Environ Mol Mutagen 19:29a.

Klein, CB; Frenkel, K; Costa, M. (1991) The role of oxidative processes in metal Carcinogenesis. 

Chem Res Toxicol 4:592-604.

Korallus, U; Lange H; Ness, A; et al. (1982) Relationships between precautionary measures and 

bronchial carcinoma mortality in the chromate-producing industry. Arbeitsmedizin, Socialmedizin, 

Preventivmedizin. 17(7):159-167. (German - Eng. summary)

Langard, S; Norseth, T. (1975) A cohort study of bronchial carcinomas in workers producing 

chromate pigments. Br J Ind Med 32:62-65.

Langard, S; Vigander, T. (1983) Occurrence of lung cancer in workers in producing chromium 

pigments. Br J Ind Med 40:71-74.

http://www.epa.gov/iris/subst/0144.htm
Laskin, S; Kuschner, M; Drew, RT. (1970) Studies in pulmonary carcinogenesis. In: Hanna, Jr., 

MG;, Nettesheim, P; and Gilbert, JR, eds. 

Levis, AG; Buttignol, M; Bianchi, V; et al. (1978) Effects of potassium dichromate on nucleic acid 

and protein syntheses and on precursor uptake in BHK fibroblasts.

Cancer Res 38:110-116.

Levy, LS; Martin, PA. (1983) The effects of a range of chromium-containing materials on rat lung. 

Sponsored by Dry Color Manufacturers' Association and others. (Unpublished)

Loeb, LA; Sirover, MA; Agarwal, SS. (1977) Infidelity of DNA synthesis as related to mutagenesis 

and carcinogenesis. Adv Exp Biol Med 91:103-115.

Lofroth, G. (1978) The mutagenicity of hexavalent chromium is decreased by microsomal 

metabolism. Naturvissenschaften 65:207-208.

Machle, W; Gregorius, F. (1948) Cancer of the respiratory system in the United States chromateproducing industry. Public Health Rep 63(35):1114-1127.

Maltoni, C. (1974) Occupational carcinogenesis. Excerpta Med Int Congr Ser 322:19-26.

Maltoni, C. (1976) Predictive value of carcinogenesis bioassays. Ann NY Acad Sci 271:431-443.

Mancuso, TF. (1975) Consideration of chromium as an industrial carcinogen.

International Conference on Heavy Metals in the Environment, Toronto, Ontario, Canada, October 

27-31. pp. 343-356.

Mancuso, TF. (1997) Chromium as an industrial carcinogen: Part 1. Am J Ind Med 31:129-139.

Mancuso, TF; Hueper, WC. (1951) Occupational cancer and other health Hazards in a chromate 

plant: A medical appraisal. In: Lung cancers in chromate workers. Ind Med Surg 20(8):358-363.

Nakamuro, K; Yoshikawa, K; Sayato, Y; et al. (1978) Comparative studies of chromosomal 

aberration and mutagenicity of trivalent and hexavalent chromium. Mutat Res 58:175-181. 

Newbold, RF; Amos, J; Connell, JR. (1979) The cytotoxic, mutagenic and clastogenic effects of 

chromium-containing compounds on mammalian cells in culture. Mutat Res

67:55-63.

National Institute for Occupational Safety and Health (NIOSH). (1975) Criteria for a 

recommended standard occupational exposure to chromium (VI). U.S. Department of Health, 

Education, and Welfare, Washington, DC.

Ohsaki, Y; Abe, S; Kimura, K; et al. (1978) Lung cancer in Japanese chromate workers. Thorax 

33:372-374.

Payne, WW. (1960a) The role of roasted chromite ore in the production of cancer. Arch Environ 

Health 1:20-26.

Payne, WW. (1960b) Production of cancers in mice and rats by chromium compounds. Arch Ind 

Health 21:530-535.

http://www.epa.gov/iris/subst/0144.htm
Petrilli, FL; DeFlora, S. (1977) Toxicity and mutagenicity of hexavalent chromium on Salmonella 

typhimurium. Appl Environ Microbiol 33(4):805-809.

Petrilli, FL; DeFlora, S. (1978) Oxidation of inactive trivalent chromium to the mutagenic 

hexavalent form. Mutat Res 58:167-178.

Raffetto, G; Parodi, S; Parodi, C; et al. (1977) Direct interaction with cellular targets as the 

mechanism for chromium carcinogenesis. Tumori 63:503-512.

Royle, H. (1975) Toxicity of chromic acid in the chromium plating industry. Environ Res 10:141-

163.

Sano, T; Mitohara, I. (1978) Occupational cancer among chromium workers. Jpn J Chest Dis 37

(2):90-101.

Satoh, K; Fukuda, Y; Torii, K; et al. (1981) Epidemiologic study of workers engaged in the 

manufacture of chromium compounds. J Occup Med 23(12):835-838.

Sorahan, T; Burgess, DC; Waterhouse, JA. (1987) A mortality study of nickel/chromium platers. 

Br J Ind Med 44:250-258.

Steinhoff, S; Gad, SC; Hatfield, GK; et al. (1983) Listing sodium dichromate and soluble calcium 

chromate for carcinogenicity in rats. Bayer AG Institute of Toxicology. (Unpublished) 

Sugiyama, M. (1992) Role of physiological antioxidants in chromium (VI)-induced cellular injury. 

Free Rad Biol Med 12:397-407.

Taylor, FH. (1966) The relationship of mortality and duration of employment as reflected by a 

cohort of chromate workers. Am J Public Health 56(2):218-229.

Todd, GE. (1962) Tobacco manufacturer's standing committee research papers. No. 1. Statistics 

of Smoking in the United Kingdom, 3rd ed. Tobacco Research Council, London.

Tsuda, H; Kato, K. (1977) Chromosomal aberrations and morphological transformation in 

hamster embryonic cells treated with potassium dichromate in vitro. Mutat Res 46:87-94.

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.

U.S. EPA. (1998) Toxicological review of hexavalent chromium. Available online at 

http://www.epa.gov/iris.

Watanabe, S; Fukuchi, Y. (1975) An epidemiological survey on lung cancer in workers of a 

chromate-producing industry in Hokkaido, Japan. Presented at International Congress on 

Occupational Health.

_VII. Revision History

http://www.epa.gov/iris/subst/0144.htm
Date

Chromium (VI)

CASRN —18540-29-9

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 change

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

08/01/1995 I.A., 

I.A.6., I.B.

EPA's RfD/RfC and CRAVE workgroups were discontinued in May 1995. 

Chemical substance reviews that were not completed by September 

1995 were taken out of IRIS review. The IRIS Pilot Program replaced 

the workgroup functions beginning in September, 1995.

04/01/1997 III., IV., V.

Drinking Water Health Advisories, EPA Regulatory Actions, and 

Supplementary Data were removed from IRIS on or before April 1997. 

IRIS users were directed to the appropriate EPA Program Offices for 

this information.

12/01/1996 I.A.7. Secondary contact removed

09/03/1998 I., II., VI. Revised RfD, RfC, carcinogenicity assessment, refs.

10/28/2003

I.A.6., 

I.B.6., 

II.D.2.

Screening-Level Literature Review Findings message has been added.

http://www.epa.gov/iris/subst/0144.htm
IRIS Home

Chronic Health 

Hazards for NonCarcinogenic Effects

Reference Dose for 

Chronic Oral 

Exposure (RfD)

• Oral RfD 

Summary 

• Principal and 

Supporting 

Studies

• Uncertainty and 

Modifying Factors

• Additional 

Studies/Comments

• Confidence in the 

Oral RfD

• EPA 

Documentation 

and Review

Reference 

Concentration for 

Chronic Inhalation 

Exposure (RfC)

• Inhalation RfC 

Summary

• Principal and 

Supporting 

Studies

• Uncertainty and 

Modifying Factors

• Additional 

Studies/Comments

• Confidence in the 

Inhalation RfC

• EPA 

Documentation 

and Review

Carcinogenicity 

Assessment for 

Lifetime Exposure

Evidence for Human 

Carcinogenicity

_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

http://www.epa.gov/iris/subst/0144.htm
• Weight-ofEvidence 

Characterization

• Human 

Carcinogenicity 

Data

• Animal 

Carcinogenicity 

Data

• Supporting Data 

for 

Carcinogenicity

Quantitative 

Estimate of 

Carcinogenic Risk 

from Oral Exposure

• Summary of Risk 

Estimates

• Dose-Response 

Data

• Additional 

Comments

• Discussion of 

Confidence

Quantitative 

Estimate of 

Carcinogenic Risk 

from Inhalation 

Exposure

• Summary of Risk 

Estimates

• Dose-Response 

Data

• Additional 

Comments

• Discussion of 

Confidence

• EPA 

Documentation, 

Review and, 

Contacts

Bibliography

Revision History

Synonyms

http://www.epa.gov/iris/subst/0144.htm