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Reference Dose for Chronic Oral Exposure( RfD ) 

## 

0472
Selenium and Compound s; CASRN 7782-49-2

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. Supp orting information and explanations of the methods used to derive the values given in IRISare provided in the guidance documents located on the IRIS website.
STATUS OF DATA FOR Selenium and Compounds
File First On-Line 03/01/1991

Oral RfD Assessment (I.A.) on-line 09/01/1991 Inhalation RfC Assessment (I.B.) no data Carcinogenicity Assessmen t (II.) on-line 07/01/1993



### _I. Chronic Health Hazard Assess ments for Noncarcinogenic Effects

_I.A. Reference Dose for Chronic Oral Exposure (RfD)
Substance Name — Selenium and Compounds CASRN — 7782-49-2 Last Revised — 09/01/1991
The oral Reference Dose (RfD) is based on the a ssumption that thresholdsexist 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 

## Integrated Risk Information System http://www.epa.gov/iris/subst/0472.htm Last updated on Thursday, August 09, 2012 

### http://www.epa.gov/iris/subst/0472.htmCritical Effect Experimental Doses* of deleterious effects during a lifetime. Plea se refer to the Background Document for an elaboration of these concepts. RfDs can also be derived for the noncarcino genic 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

Clinical selenosis
Human Epidemiological Study
Yang et al., 1989b NOAEL: 0.015 mg/kg/day
LOAEL: 0.023 mg/kg/day 3 1 5E-3 mg/kg/day

* Conversion Factors: NOAEL (0.853 mg /day) and LOAEL (1.261 mg/day) calculated from regression analysis (log Y = 0.767log X - 2.248, where Y = blood selenium and X = selenium intake) as detailed in Yang et al. (1989a) based upon the correlation (r = 0.962) between dietary selenium intake and blood selenium level for data showing incidence of clinical selenosis in adults based on an average adult body weight of 55 kg (Yang et al., 1989b).
__I.A.2. Principal and Supporting Studies (Oral RfD)
Yang, G., S. Yin, R. Zhou, et al. 1989b. Studies of safe maximal daily dietary Se-intake in a seleniferous area in China. II. Relation between Se- intake and the manifestation of clinical signs and certain biochemical al terations in blood and urine. J. Trac e Elem. Electrolytes Health Dis. 3 (2): 123-130.
Yang et al. (1989b), in a follow-up to an earlie r study (Yang et al., 1983), studied a population of approximately 400 individua ls living in an area of China wi th unusually high environmental concentrations of selenium (Se). The subjects were evaluated for c linical and biochemical signs of Se intoxication. Three geographical areas with low,medium and high selenium levels in the soil and food supply were chosen for comparison in th e studies. The earlier Ya ng et al. (1983) study was conducted in response to en demic selenium intoxication in tw o separate areas with sample sizes of only 6 and 3. Comparis ons were then made to a selenium-adequate area (n=8) and lowselenium area (n=13). The Yang et al. (1989a,b) studies provide a much larger sample size and include additional analysis of tissu e selenium levels. This allows a more accurate estimation of the dose-response relationship obse rved for selenium toxicity. Se lenium levels in soil and approximately 30 typical food types commonly eaten by the exposed population showed a positive correlation with blood and tissue Se le vels. The daily average Se intakes, based on lifetime exposure, 70, 195 and 1438 ug for adult males and 62, 198 and 1238 ug for adult females in the low-, medium- and high-selenium areas, respectively. Significant correlations demonstrated between Se concentrations of vari ous tissues were used to estimate the minimal daily Se intake values that elicited various alte rations in biochemical parameters indicative of possible Se- induced liver dysfunction (i.e., prolon gation of clotting timeand serum glutathione titer) and clinical signs of sele nosis (i.e., hair or nail loss, mo rphological changes of the nails, etc.). In this manner, a ma rginal safe level of daily Se intake was estimated. 

### http://www.epa.gov/iris/subst/0472.htmAnalysis of the results indicated that perisistent clinical signs of selenosis were observed only in 5/349 adults, a potentially sensit ive subpopulation. The blood se lenium concentration in this group ranged from 1.054 to 1.854 mg/L with a mean of 1.346 mg/L. Cl inical signs observed included the characteristic "garlic odor" of exce ss selenium excretion in the breath and urine, thickened and brittle nails, hair and nail loss, lowered hemoglobin levels, mottled teeth, skin lesions and CNS abnormalities (peripheral an esthesia, acroparesthe sia and pain in the extremities). Alterations in the measured bioche mical parameters occurred at dietary intake levels of 750-850 ug/day. These al terations were described as a de lay in prothrombin time, i.e., increase in blood coagulation time and reductio n in blood glutathione concentration. However, these indicators were poorly ch aracterized and are not typically used as an index for clinical selenosis resulting from chronic exposure toselenium (NAS, 1989). Based upon the blood selenium levels shown to reflect clinical signs of sele nium intoxication, a whole blood selenium concentration of 1.35 mg/L corresp onding to 1.261 mg of daily selenium intake is indicative of the lowest correlative selenium intake causing overt signs of se lenosis. The next lowest whole blood selenium concentrat ion of 1.0 mg/L, corresponding to 0.853 mg selenium/day, produces no clinical signs of selenosis. The NOAEL for this study is 0.85 mg Se/day and the LOAEL is 1.26 mg Se/day.
A group of 142 volunteers in So uth Dakota and Wyoming were re cruited by Longnecker et al. (1991) at random from households listed in a te lephone directory or from ranches with suspected high selenium intake based on previous cases of livestock selenosis. The geographical areas were chosen because of known seleniferous topsoil and high concentrations of selenium in plants and food. The subjects were followed for 1 year an d completed health ques tionnaires, underwent physical examinations, provided blood samples for clinical assessment, and provided blood, urine, toenails and duplicate-pl ate food collections for selenium an alysis. The average selenium intake was 239 ug/day, approximately 2-3 times higher than the national average. The concentration of selenium in whole blood, serum, ur ine and toenails and the amount in diet were highly correlated. Blood selenium concentration was highly correla ted with selenium intake. The correlation was very similar to that reported by Yang et al. ( 1989a). Liver function (proth rombin time and alanine aminotransferase, aspartate aminotransferase , gamma glutamyltransferase and alkaline phosphatase), hematologic functon (leukocyte co unt, hemoglobin and hematocrit) and clinical chemistry (sodium, potassium and chloride concen tration) were not found to be altered as a result of selenium intake. High regression coef ficient predictor variable s for selenium toxicity (muscle twitching, paresthesia, nail loss, nail lines , hair loss and garlic breath) were not found in increased frequency for this population. No sign s of selenium toxicity were found in this population, including individuals whose selenium intake was as hi gh as 724 ug/day. This report corroborates that of Yang et al. (1989b), which showed that a selenium intake of up to 853 ug/day is not associated with characteristic nail or hair loss typical of selenium intoxication.

__I.A.3. Uncertainty and Mo difying Factors (Oral RfD)
UF — An uncertainty factor of 3 was applied to the NOAEL to acco unt for sensitive individuals. A full factor of 10 was not deemed necessary since similar NOAELs were identified in two moderately-sized human populations exposed to se lenium levels in excess of the RDA throughout a lifetime without apparent c linical signs of selenosis.

MF — None

__I.A.4. Additional Stud ies/Comments (Oral RfD)
The essentiality for selenium has been well-documented in livestock based upon the alleviation of specific deficiency cond itions by selenium supp lementation of the diet (Combs and Combs, 1986). 

### http://www.epa.gov/iris/subst/0472.htmSelenium has been clearly demonstrated to be a cofactor of glutathione peroxidase, a hydrogen and lipid peroxide reducing enzyme and is th erefore essential (Rotru ck et al., 1973). Human requirements for selenium were not conclusively esta blished until 1979 when an association was made between low selenium status and cardiomyopathy (Keshan disease) in China for young children and women of child-be aring age (Keshan Disease Rese arch Group, 1979a,b). More recently, iatrogenic episodes of selenium defici ency have been reported in patients receiving intravenous total parenteral admi nistration of feeding solutions devoid of selenium. Symptoms included low glutathione peroxidase activity and low selenium levels in erythrocytes (Levander and Burk, 1986), muscular weakness and discomfort (van Rij et al., 1979) and cardiomyopathy (Johnson et al., 1981). Itis important to note that glutathione peroxida se activity is a valid indicator of human selenium status only in populations with relatively low selenium intakes, since the enzyme activity platea us at adequate selenium intake levels (Whanger et al., 1988), thereby precluding the use of this biochemical indicato r under excessive seleni um intake situations.
The NAS (1989) has determined the recommended dietary allowance for selenium to be 0.87 ug/kg, or approximately 70 and 55 ug/day for the reference adult North American male and female, respectively. Requirements for selenium increase during pregnancy to 65 ug/day and for lactation to 75 ug/day. Selenium requirements for infants and children vary according to age. However, based on the referenc e weights of NHANES II, thes e populations demonstrate an increased requirement per unit weight relative to adults. For infants, the selenium requirement is 1.67 ug/kg and for children the requirement rang es from 1.07-1.53 ug/kg. It should be noted that the most recent RDA for se lenium did not consider the 1989 results of Yang et al. (1989a,b) discussed above, but an earlier preliminary report by the sameauthors (Yang et al., 1983).
Yang et al. (1983) reported clinical signs of selenosis (i.e., loss of hair and nails) in approximately 50% of a population of 248 inhabi tants living in Ensh i County, Hubei Province of the People's Republic of China. Selenosis wa s reported in the highest seleni um contaminated area where the average daily Se intake was 5.0 mg/day (range3.2-6.7), but no sele nosis occurred when the average intake was 0.750 mg/day (range 0.240- 1.51). These estimates, however, were based upon estimates of intake from only 6 and 3 inhabitants in the hi gh and low contaminated areas, respectively. Yang et al. (1989b) reported prol onged clotting time an d serum glutathione and these biochemical changes were in dicated as adverse effe cts of selenium exposure. Glutathione is a strong nucleophile that reacts well with soft electrophiles an d is an important conjugate-forming compound for the detoxification and excretion of electrophilic metabolites and metabolically produced oxidizing agents. If glutathione is depleted or markedly reduced in the liver, the hepatotoxicity of these compound s would likewise be expected tobe enhanced (Ketterer et al., 1983). However, the significance of decreased serum glutathione is not well characterized and should not be used in this context as a biochemica l marker of selenium toxicity. Likewise, there is no indication that prothrombin activity is affected by excess selenium ad ministration (Longnecker et al., 1991). Furthermore, the de scription of this effect in Ya ng et al. (1989b) was based on a population for which there is insufficient docume ntation of normal clotting times in the general Chinese population.
Selenium toxicity has been clinically described according to three types: acute selenosis, subacute selenosis and chronic se lenosis. The acute condition is caused by consuming relatively high amounts of selenium over a short period of time. After the onset of this condition, walking becomes unsteady, cyanosis of the mucous membranes occurs an d labored breathing is usually seen sometimes resulting in deat h. Pathological findings include congestion of the liver, endocarditis and myocarditis, dege neration of the sooth musculature of the gastrointestinal tract, gallbladder and bladder, and erosion of th e long bones (Francke and Moxon, 1936). 

### http://www.epa.gov/iris/subst/0472.htmSubacute selenosis occurs from exposure to large doses of Se over a longer period of time resulting in neurological dysfunction (impaired vision, ataxia, disorientation) and respiratory distress. It is typically seen most frequently in grazing livestock feeding upon Se-accumulating plants and has been referred to as "bli nd staggers" (Rosenfe ld and Beath, 1964).
Prolonged exposure to more moderate levels of se lenium result in skin lesions involving alopecia, hoof necrosis and loss, emacia tion and increased serum transa minases and alkaline phosphatase in animals. In man, the condition is characte rized by chronic dermatit is, fatigue, anorexia, gastroenteritis, hepatic degenerati on, enlarged spleen and increase d concentrations of Se in the hair and nails (Harr and Muth, 1972).
Selenium exists naturally in a number of oxidat ion states, thereby accoun ting for the different forms of selenium important to living organisms byoral ingestion. In the -2 oxidation state, selenium can be found as hydrogen selenide (H 2Se), sodium selenide (Na2Se), di-[(CH3)2Se] and trimethyl selenium [(CH3)3Se] and various selenoamino acids such as selenomethionine, selenocysteine, Se-methyl seleno cysteine, selenocystathionine and selenotaurine. Elemental selenium and the dipeptide selenodi glutathione have an oxidation state of 0. In the +4 oxidation state, selenium can exist as selenium dioxide (SeO2), selenious acid (H2SeO3) or as sodium selenite (Na2SeO3). Finally, in its most oxidized state (+6), selenium can be found as selenic acid (H2SeO4) or as sodium selenate (Na2SeO4).
The toxicity of selenium has be en consistently well documented . However, some early studies reported that selenium may be a carcinogen. Ne lson et al. (1943) showed that rats fed diets containing Se as seleniferouswheat developed hepatic tumors and low-grade carcinomas in 11/53 animals. This work has subsequently been criticized due to low-protein content and relatively high levels of Se in the diet (5, 7 or 10 ppm Se), a poorly characterized source of selenium, and in general poor ex perimental design. The authors reported no encapsulation or metastases and in fact noted their own diffi culty in determining th e difference between hyperplasia and tumor. Another early investigation by Seifter et al. (1946) reported several thyroid tumors and adenomatous hy perplasia in livers of rats fed 0.05% bis-4- ac etylaminophenyl selenium dihydroxide fo r 105 days. This organic selenium compound was suspected of having goitrogenic properties but its carcinogenic effect has not been further confirmed to be attributable to the selenium in the molecule.
The first animal experiment which demonstrated anticarcinogenic effe cts of selenium was performed by Clayton and Baumann (19 49). An approximate 50% reduction in dimethylaminoazobenzene-induced tumor incidence o ccurred in rats fed a diet supplemented with 5 ppm Se as selenite. Additional evidence subsequently reported, further illustrated the inhibitory effect of selenium on transp lantable tumors in rats (Weisberger and Suhrland, 1956a) and leukemia in humans (Weisberger and Suhrland, 1956b). The National Canc er Institute sponsored an extensive study on selenium toxicity in rats in order to resolve the issue of selenium carcinogenicity. Diets containing up to 8 ppm se lenium did not increase tumor incidence (Tinsley et al., 1967; Harr et al., 1967). Since 1970, there has been an in creased interest in characterizing the anti- carcinogenic and anti-tumorigenic properties of selenium. The number of reports characterizing these properties are too num erous to discuss in detail here. The reader is referred to a review by Milner and Fico (1987) for a more comprehensive treatment of the database.
The essentiality and toxicity of selenium varies according to the valence state of selenium when incorporated into biomolecules and the form in which selenium is fed or administered. This is especially true when comparing the LD50 value as an index of toxicity for the various selenium compounds. Although it is difficult to make an assessment for several selenium compounds by a 

### http://www.epa.gov/iris/subst/0472.htmsimilar mode of administ ration in a common spec ies, there is general agreement that sodium selenite, sodium selenate, sele nomethionine and selenoglutathione are among the more toxic species (Combs and Combs, 1986). The relative potency of syst emic toxicity for selenium compounds is also similar in expe riments examining potency of anti-tumorigenic activity. In vitro examination of potency of effectof selenium compounds on incu bated Ehrlich ascites tumor cells (EATC) showed that sodium seleni te is more efficacious in significantly reducing EATC viability than an equivalent concentration of sodium selenate. Al though selenium dioxide, selenomethionine and selenocystine ultimately de creased viability of the EATC, nearly 50% more incubation time was required fo r the same effect (Poirier and Milner, 1979). The same authors investigated the relative potency of various se lenium compounds administered intraperitoneally on EATC growth in vivo. Sodium selenite and selenodiglutathione (an intermediate of selenium metabolism) were the most effect ive forms of selenium in preventing EATC propagation. Sodium selenide, dimethyl selenideand selenocystine were no t effective in inhibiting EATC growth (Poirier and Milner, 1983). Similar relative potency results have been repo rted in in vitro systems for canine mammary cells (Fico et al., 1986) and human mammary cells (Wat rach et al., 1984).
Since selenium has been repo rted to cause growth retardation, decreased fertility, embryotoxicity, fetotoxicity and teratogenic effects in animals, Yang et al. (1989b) made the following observations: Malformation in chickens hatched from locally produced eggs did occur; however, teratogeneic effects in human infants we re never seen in this area although Se has been reported to be transmitte d through the placenta to the fe tus in animals. These findings confirm those reported by Yang et al. (1983) in which chicken eggs from this same area were reported to have very low hatchability and somedeformed embryos in those that did hatch.
The developmental toxicity of selenomethionine wa s investigated by Tarantal et al. (1991) in non-human primates. Forty pregnant long-taile d macaques were dosed daily by nasogastric intubation with 0, 0.025, 0.150 or 0.3 mg sele nium/kg as selenomethioni ne through gestational days 20-50. Dams were examined clinically and the pregnancies of two to three dams within each test group were followed to term (gestational day 165). All other dams were hysterectomized on gestational day 100. Neonates de livered at term were examined for morphometric, neurologic, behavioral and ophthalmologic effects on days 1, 8, 15, 22 and 30. Pregnancy loss among treated animals was not significantly different from concur rent or historical cont rols. No statistically significant treatment-related effe cts were observed at necropsyon gestational day 100. There were no significant maternal or fetal developm ental effects or teratoge nesis found up to 0.3 mg/kg selenium, the highest dose tested.
Halverson et al. (1966) fed 60-70 g male, post -weanling Sprague-Dawleyrats selenium as selenite or seleniferous wheat ad libitum at 1.6, 3.2, 4.8, 6.4, 8.0, 9.6 or 11.2 ppm of selenium (13, 27, 40, 67, 81 or 94 ug/kg/day , respectively). Levels of selenium up to 4.8 ppm showed no effect. At 8.0 ppm selenium as seleniferous wheat, there was an observed decrease in liver weight, increase in spleen weight, and decreasein hemoglobin. Mortality was observed in the groups fed 8.0, 9.6 and 11.2 ppm selenium as seleniferous wheat at incidences of 1/8, 5/8 and 8/8, respectively. The incidences of mortality re ported for groups fed 8.0 and 9.6 ppm selenium as selenite were 1/8 and 1/10, respectively. A si gnificant growth reductio n was reported for both selenium sources at 6.4 ppm and higher, although feed utilizatio n was not decreased. No other effects were reported for th e rats fed sodium selenite.
Schroeder and Mitchener (1971) administered 3 ppm selenium as selenate (390 ug/kg/day) to CD mice through four generations. Maternal effects were not observed. There was a significant increase in young deaths in the F1 generation an d an increase in numbers of runts in generations F1 through F3. By the F3 generation there was also a decrease in breeding events. 

### http://www.epa.gov/iris/subst/0472.htmRosenfeld and Beath (1954) admini stered selenium as potassium se lenate to sires and pregnant rats through five breeding cycles at 1.5, 2.5 or 7.5 ppm selenium (75, 125 or 375 ug/kg/day). No effect was observed on reproducti on, the number of young reared or on the reprod uction of two successive generations of dams and sires in groups receiving 1.5 ppm selenium. In the group receiving 2.5 ppm selenium, the was a 50% reductio n in the number of young reared. At 7.5 ppm there was a decrease in fertility of the females but not males, a decrease in the number of survivors and a reduction in the rate of growth in the young.
Nobunaga et al. (1979) administered 3 or 6 pp m selenium (390 or 780 ug/kg/day, respectively) as selenite to IVCS mice for 30 days prior tomating and throughout gestation. On day 18 of gestation, maternal mice were sacrificed and the embryos removed. Number of litters, total implants, total implants per dam, dead fetuses, dead embryos, re sorptions, surviving fetuses (% to total implants), litter size, gross malformati ons and skeletal anomalie s were not significantly different for either selenium-treated or contro l mice. The only significant effect noted was a decrease in the body weight of survivin g fetuses in mice gi ven 6 ppm selenium.

__I.A.5. Confidence in the Oral RfD
Study — Medium Database — High RfD — High
Confidence in the chosen principal study is medium. Although this is a human epidemiological study in which a sizable population with sensitive subpopulations was studied, there are still several possible interactions that were not fully accounted for, e.g., fluo ride intake and protein status. Also, except for clinical signs of sele nosis there are no othe r reliable indicators, biochemical or clinical, of selenium toxicity. Co nfidence in the database is high because many animal studies and epidemiolo gic studies (reviewed by Comb s and Combs, 1986) support the principal study. An additional human study with a freestanding NOAEL (Longnecker et al., 1991) strongly corroborates the NOAEL iden tified in the principal study. Therefore, high confidence in the RfD is selected based upon supp ort of the critical study and the high level of confidence in the database.

__I.A.6. EPA Documentation and Review of the Oral RfD
Source Document — This assessment is not presented in any existing U.S. EPA document.

Other EPA Documentatio n — U.S. EPA, 1985
Agency Work Group Review — 01/20/1988, 03/22/1989, 09/21/1989, 11/14/1990, 03/27/1991
Verification Date — 03/27/1991
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 Selenium and Compounds conducted in September 2002 identified one or more significan t new studies. IRIS users may request the refe rences for those studies from the IRIS Hotline at hotline.iris@epa.gov or (202)566-1676.

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

### http://www.epa.gov/iris/subst/0472.htmPlease contact the IRIS Hotline for all questions co ncerning 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)
Substance Name — Selenium and Compounds CASRN — 7782-49-2

Not available at this time.



### _II. Carcinogenicity Asse ssment for Lifetime Exposure
Substance Name — Selenium and Compounds CASRN — 7782-49-2 Last Revised — 07/01/1993
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 extrap olation procedure and is presente d as the risk per (mg/kg)/day. The unit risk is the quantitative estimate in terms of either risk per ug/L dr inking water or risk per ug/cu.m air breathed. The third form in which ri sk is presented is a drinking water or air concentration providing 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 (E PA/600/8-87/045) and in the IRISBackground Document. IRIS summaries developed since the pu blication 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.

NOTE: This assessment is for the following compounds: Sele nium (CASRN 7782- 49-2); sodium selenate (CASRN 13410-01-0); so dium selenite (CASRN 10102-18-8) ; selenious acid (CASRN 7783-00-8); selenic acid (CASRN 7783-08-6) ; sodium selenide (CASRN 1313-85-5).

_II.A. Evidence for Human Carcinogenicity
__II.A.1. Weight-of-Evid ence Characterization
Classification — D; not classifiable as to carcinogenicity in humans
Basis — Based on inadequate human data and inadeq uate evidence of carcinogenicity in animals. The evidence for various selenium compounds in animal and mutagenicity studies is conflicting and difficult to interpret; however, evidence for selenium sulfide is sufficient for a B2 (probable human carcinogen) classification.
__II.A.2. Human Carcinogenicity Data 

### http://www.epa.gov/iris/subst/0472.htmInadequate. Data on the potential carcinogenicity of selenium and various selenium compounds in humans are inadequate. Epidemiological studies have evaluated selenium in blood and cancer death rates in areas of high vs. low naturally- occurring selenium. However, these studies have limited value because they do not assess specific selenium compounds or co rrelate exposure with cancer risk.
Several investigators have studie d the association between serum se lenium and the risk of cancer through prospective, case-control an d nested case- control studies. Analysis of blood serum levels indicated that patients with cancer, particular ly gastrointestinal cancer, prostatic cancer, or Hodgkin's lymphoma, had significantly lower blood se lenium levels in blood than healthy patients (Shamberger et al., 1973; Salonen et al., 1984; Kok et al., 1987; Willet et al., 1983; Willet and Stampfer, 1986). The risk of cancer for men (Kok et al., 1987) or fo r all subjects (Willet et al., 1983) in the lowest quintile of serum selenium wa s twice that of subjectswith higher levels.
Geographic correlational studies have compared cancer mortality in areas of high vs. low levels of naturally-occurring selenium. In an ecological study Shamberger and Frost (1969) reported that an inverse relationship existed between cancer death rates and the selenium concentrations in foliage plants of several Canadian provinces. The human cancer death rate in provinces with selenium-containing plants was 122.2 +/- 7.8 (presumably per 100,00 0 population although this was not specified), while in the provinces devoid of these plants, the human death rate was 139.9 +/- 4.0.
In an ecological study Shamberger and Willis(1971) reported that there was a correlation between decreased cancer death ra tes in humans and an increase in the selenium in the forage crops in California. In high-selenium areas (selen ium 0.11 ppm of forage crops) the cancer death rate per 100,000 was 141.2. In the medium-selen ium areas (0.05-0.10 ppm) the cancer death rate was 190.1. In low-selenium areas (0. 02-0.05 ppm) the cancer death rate was 233.0. Shamberger and Willis (1971) also investigated th e ratio of observed to expected cancer death rates by anatomic site for men in 17 paired citi es including high- and low-selenium areas. The anatomic sites that would come in to contact with dietary selenium , such as pharynx, esophagus, stomach, bladder and inte stine, showed a substantially lower rate ratio in the high- selenium cities than in the low-selenium cities. Other ecol ogical and prospective st udies have correlated an increased incidence of colon, breast and other forms of cancer in humans in geographic areas where selenium is deficient and a lowered cancer incidence with higher selenium concentrations (Schrauzer and Ishmael, 1974; Shamberger, 1976; Schrauzer et al., 1976; Jansso n et al., 1978; Yang et al., 1983).
In a study of approximately 300 em ployees exposed to sele nium (form not specified) in a rectifier (electronics) process over a 26-year period, only 17 deaths occurred, 6 of which were because of cancer (Glover, 1970). This number , however, is not statistically different from the 5.1 deaths expected based on national mortal ity rates. The source of the mortality rates was not specified. Several toxic effects including pulmonary irritation, epigastric pain and dermal irritation and dermatitis were associated with selenium exposure in men, bu t no carcinogenic effect was reported.

__II.A.3. Animal Carcinogenicity Data
Inadequate. The carcinogenicity of selenium co mpounds has been evaluated in several animal studies. However, the data are conflicting an d difficult to interpret because of apparent anticarcinogenic activity and high toxicity of someselenium salts. In addi tion, comparison of the available data is difficult because several differe nt salts with varying de grees of bioavailability were used in the assays. 

### http://www.epa.gov/iris/subst/0472.htmIn a 2-year dietary study repo rted by Nelson et al. (1943), Osborne-Mendel rats (sex not specified) were fed selenium in the form of seleniferous corn or wheat or ammonium potassium selenide at 5-10 ppm. Survival was lower in th e treated rats; 53/126 (42%) rats fed selenium survived 18 months or longer compared with 14/18 (78%) control rats . Of the 53 surviving selenium-treated rats, 43 (81%) developed liver cirrhosis and 11 (21%) developed hepatocellular adenoma or carcinoma. All 11 animals with tumors also had liver cirrhosis. None of the 14 control animals surviving 2 years developed liver tumors. Only pooled group data were reported and no statistical analysis was reported.
No tumors developed in a total of 1437 Wistar rats fed sodium selenite or sodium selenate in the diet at levels of 0.5-16 ppm for their lifetime (Harr et al., 1967; Tinsley et al., 1967). Nonneoplastic liver effe cts such as hyperemia, cellular de generation, binucleation, and mild proliferation of hepa tocytes were observed at concen trations of 4 ppm and higher.
Long-Evans rats (approximately 50/sex/group at study initiation) received 2 ppm (as selenium) sodium selenate or sodium seleni te in drinking water for 1 year, then 3 ppm for the remainder of the study (Schroeder and Mitchener, 1971). Th e treatment of the control group was not discussed. The animals wereobserved for the duration of thei r natural lifespan, approximately 36 months, although one selenate-treated female live d for 5 years. Selenite produced 50% mortality in males by 58 days. At this time, 2 ppm selenatewas substituted for selenite in the male group. The concentration of selenium was raised to 3 ppm in this group when the animals were 1 year old; however, the high mortality rendered the group size too small for further statistical analysis. Selenite produced 50% mortal ity in females by 348 days; se lenite- treated females were sacrificed at 23 months due to high mortality. Selenate produced 50% mortality in females by 1014 days and in males by 962 days. In the cont rol groups 50% mortality was achieved by 872 and 853 days in females and males, respective ly. Survival of rats receiving selenate was comparable to controls and medi an lifespan was increa sed by >100 days. Body weights of treated males were comparable to controls throughout th e study. Body weights of females fed selenate were significantly greater than controls at 24 and 36 months; body weights of females fed selenite were significantly less than controls at all times but 18 months.
Incidence of all tumors and of malignant tumorswas significantly increased in the selenatetreated rats compared with the controls. Incide nce of all tumors in controls, selenate- and selenite-treated rats was 20/65 (30.8%), 30/48 (62.5%) and 4/32 (1 2.5%), respectively. Incidence of malignant tumors in the same groups was 11/65 (16.9%), 20/48 (41.7%) and 4/32 (12.5%), respectively. The earlie st tumor occurred on day 833 in the control males, on day 633 in the control females, on day 344 in selenate males and on day 633 in selenate females. The shortened survival time of the selenite groups was thought to be responsible for the small number of tumors. This study is considered inad equate because only the heart, lung, liver, kidney and spleen tissues from animals necropsied were examined histol ogically, and an increase in longevity was observed in se lenate-treated female rats.
Schroeder and Mitchener (1972) administered 3 pp m sodium selenate or sodium selenite in drinking water to Swiss mice (50/sex/group). Bo dy weights of selenate -treated animals were comparable to controls. Body weights of males fe d selenite were signific antly increased compared with controls, but body weights of females fed selenite were si gnificantly decreased compared with controls. Longevity in males fed selenate wa s increased compared with controls. Longevity in females fed selenate increased, but longevity in females fed sele nite decreased compared with controls. When compared to controls, there was no significant increase in total tumor incidence or malignant tumor incidence observed in selenium- (form not specifie d) treated mice. In the control group 23/119 (19%) had tumors (10/119 (8%) mali gnant tumors). Seleni um-fed mice showed 13/88 (15%) tumors (all were malignant). In se lenium-treated group 8/13 malignancies were 

### http://www.epa.gov/iris/subst/0472.htmlymphoma or leukemia, 4/13 were papillary or alveologenic adenoc arcinoma and 1/13 an osteosarcoma. In the control group there were tw o incidences of lymphoma or leukemia, 7 of lung carcinoma and 1 carcinoma of unknown origin. The 13 benign tumors included breast and ovary tumors.
__II.A.4. Supporting Data for Carcinogenicity

Selenium is an essential micron utrient for several species, incl uding humans, and is part of several enzymes such as glutathi one peroxidase, an enzyme involved in cellular defense against oxidative damage, and heme oxidase. While low do ses of selenium are esse ntial, high doses of selenium or a deficiency of dietary selenium ma y cause a toxic response. Additionally, selenium may be protective against tumor development. The greatest daily exposure to selenium is via food. Bioavailability of selenium is dependent on numerous factors, including the intake levels, chemical form and nutritional status. Organic fo rms of selenium are more bioavailable than inorganic forms; selenates and se lenites are the inorganic forms more readily absorbed. Sodium selenate and selenite are soluble in water, but the extent to which they are absorbed dermally or through the gastrointestinal tract has not been fully elucidated (U.S. EPA, 1989).
Shamberger (1985) reported that the oral administration of 0.1- 6 ppm or dermal application of 0.005% of selenium reduced incidenc es of skin, liver, tracheal, inte stinal and lung tumors induced by several carcinogens in rats, mice and hamsters. Shamberger theori zed that selenium may reduce cellular damage caused by peroxidation of fat. In another study, natural killer (NK) cell activity was significantly increased in female ra ts administered 0.5 or 2.0 ppm selenium (sodium selenate) in the drinking water for 10 weeks (Kol ler et al., 1986), suggestin g to the authors that NK-sensitive tumors may be prevented by using selenium therapy.
Data on the mutagenicity of sele nium and its compounds are equivo cal. Selenate and selenite (12 uM) were mutagenic in a revers e mutation assay using Salmone lla typhimurium strains TA98, TA100 and TA1537 (Noda et al., 1979) in the absence of rat hepatic homogenates. In a second assay, sodium selenate, but not sodium selenite, was mutagenic; the S. typhimurium strains used were not reported (Lofroth and Ames, 1978). Selenite (selenious acid and sodium selenite) produced DNA damage in Bacillussubtilis strains 17A and 45T; ho wever, selenate (selenic acid and sodium selenate) was negative in the Rec assay (Nakamuro et al., 1976).
Sodium selenide, sodium selenite, and sodium sele nate (in order of decreasing activity) caused an increase in unscheduled DNA synthesis in the presence or absence of glutathione in Chinese hamster ovary cells at co ncentrations of 1.0E-4 M (Whiting et al., 1980). Increased chromosomal aberrations were also produced by sodium seleni te at E-5 M in rat lymphocytes (Newton and Lilly, 1986) and by sodium selenite, sele nious acid, selenic acid, and se lenium oxide at 2.6E-6 M in human lymphocytes (Nakamuro etal., 1976). Sodium selenite produced an increase in chromosomal aberrations in the bone marrow of rats administered a total of 10-12 mg/kg intravenously (near-lethal dose s) (Newton and Lilly, 1986). Sele nium (elemental), selenium dioxide, sodium selenide, and so dium selenite (in order of de creasing activity) induced an increase in SCEs in human whole-blood cultures ; sodium selenate was not mutagenic in this assay (Ray and Altenburg, 1980).

_II.B. Quantitative Estimate of Carcin ogenic Risk from Oral Exposure

None 

### http://www.epa.gov/iris/subst/0472.htm_II.C. Quantitative Estimate of Carcinog enic Risk from Inhalation Exposure

None

_II.D. EPA Documentation,Review, and Contacts (C arcinogenicity Assessment)

__II.D.1. EPA Documentation
Source Document — U.S. EPA, 1980, 1984, 1989

The 1989 Health and Environmental Effects Document on Selenium and Compounds has received OHEA review.
__II.D.2. EPA Review (Carcinogenicity Assessment)
Agency Work Group Review — 11/09/1989, 03/07/1990
Verification Date — 03/07/1990
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 Selenium and Compounds conducte d in September 2002 did not identi fy any critical new studies. IRIS users who know of important new studies ma y 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 co ncerning 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
Substance Name — Selenium and Compounds CASRN — 7782-49-2 Last Revised — 06/01/1991

_VI.A. Oral RfD References
Clayton, C.C. and C.A. Baumann. 1949. Diet and azo dye tumors: Ef fect of diet during a period when the dye is not fed. Cancer Res. 9: 575-582.
Combs, G.F. and S.B. Combs. 1986. Effects of Selenium Excesses, Chapter 11. In: The Role of Selenium in Nutritio n. Academic Press, New York. p. 463-525. 

### http://www.epa.gov/iris/subst/0472.htmFico, M.E., K.A. Poirier, A.M. Watrach, M.A. Wa trach and J.A. Milner. 1986. Differential effects of selenium on normal and neop lastic canine mammary cells. Cancer Res. 46: 3384-3388.
Francke, K.W. and A.L. Moxon. 1936. A comparis on of the minimum fatal doses of selenium, tellurium, arsenic and vanadium. J. Pharmacol. Exp. Ther. 58: 454-459.
Halverson, A.W., I.S. Palmer an d P.L. Guss. 1966. Toxicity of se lenium to post-weanling rats. Toxicol. Appl. Pharmacol. 9: 477-484.
Harr, J.R. and O.H. Muth. 1972. Se lenium poisoning in domestic an imals and its relationship to man. Clin. Toxicol. 5(2): 175-186.
Harr, J.R., J.F. Bone, I.J. Tinsle y, P.H. Weswig and R.S. Yamamo to. 1967. Selenium toxicity in rats. II. Histopathology. In: Sele nium in Biomedicine, O.H. Muth, Ed. AVI, Westport, CT. p. 153- 178.
Johnson, R.A., S.S. Baker, J.T. Fallon, et al. 1981. An occidental case of cardiomyopathy and selenium deficiency. N. En gl. J. Med. 304(20): 1210-1212.
Keshan Disease Research Group of the Ch inese Academy of Medi cal Sciences. 1979a. Observations on effect of sodium selenite in prevention of Keshan disease. Chin. Med. J. 92(7): 471-476.
Keshan Disease Research Group of the Ch inese Academy of Medi cal Sciences. 1979b. Epidemiologic studies on the etiologic relationship of selenium and Keshan disease. Chin. Med. J. 92(7): 477-482.
Ketterer, B., B. Cole s and D.J. Meyer. 1983. The role of glutathione in deto xication. Environ. Health Perspect. 49: 59-69.
Levander, O.A. and R.F. Burk. 1986. Report on the 1986 A.S.P.E.N. Research Workshop on Selenium in Clinical Nu trition. J. Parenter. Enteral Nutr. 10(6): 545-549.
Longnecker, M.P., P.R. Taylor, O.A. Levander et al. 1991. Selenium in diet, blood, and toenails in relation to human health in a selenifero us area. Am. J. Clin. Nutr. 53: 1288-1294.
Milner, J.A. and M.E. Fico. 1987. Selenium and tumorigenesis. In: Selenium in Biology and Medicine: Proceedings of the Third International Symposium on Selenium in Biology and Medicine, G.F. Combs Jr., J.E. Spallholz, O.A. Levander and J.E. Oldfield, Ed. Van Nostrand Reinhold, New York. p. 1034- 1043.
NAS (National Academy of Sciences). 1989. Recommended Dietary Allowances, 10th ed. National Academy Press, Washin gton, DC. p. 217-224.
Nelson, A.A., O.G. Fitzhugh and H.O. Calvery. 1943. Liver tumors following cirrhosis caused by selenium in rats. Cancer Res. 3: 230-236.
Nobunaga, T., H. Satoh and T. Suzuki. 1979. Effects of sodium selenite on methylmercury embryotoxicity and teratogeni city in mice. Toxicol. Appl . Pharmacol. 47(1): 79-88.
Poirier, K.A. and J.A. Milner. 1979. The effect of various sele no- compounds on Ehrlich ascites tumor cells. Biol. Trac e Elem. Res. 1: 25-34. 

### http://www.epa.gov/iris/subst/0472.htmPoirier, K.A. and J.A. Milner. 198 3. Factors influencing the antitumo rigenic properties of selenium in mice. J. Nutr. 113: 2147-2154.
Rosenfeld, I. and O.A. Beath. 1954. Effect of selenium on reproduction in rats. Proc. Soc. Exp. Biol. Med. 87: 295-297.
Rosenfeld, I. and O.A. Beath. 1964. Selenium: Geobotany, Biochemistry, Toxicity and Nutrution. Academic Press, New York. p. 198-208.
Rotruck, J.T., A.L. Pope, H.E. Ganther, A.B. Swanson, D.G. Ha feman and W.G. Hoekstra. 1973. Selenium: Biochemical role as a component of glutathione pero xidase. Science. 179: 588-590.
Schroeder, H.A. and M. Mitchene r. 1971. Toxic effects of trace el ements on the reproduction of mice and rats. Arch. Envi ron. Health. 23(2): 102-107.
Seifter, J., W.E. Ehrich, G. Hudyma and G. Muel ler. 1946. Thyroid adenomas in rats receiving selenium. Science. 103(2687): 762.
Tarantal, A.F., C.C. Willhi te, B.L. Lasley et al. 1991. Developmen tal toxicity of L-selenomethionine in Macaca fascicularis. Fund. Appl. Toxicol. 16: 147-160.
Tinsley, I.J., J.R. Harr, J.F. Bo ne, P.H. Weswig and R. S. Yamamoto. 1967. Se lenium toxicity in rats. I. Growth and longevity. In: Selenium in Bi omedicine, O.H. Muth, Ed. AVI, Westport, CT. p. 141-152.

U.S. EPA. 1985. Health Effects Assessment for Selenium (a nd Compounds). Prepared by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Emergency and Remedial Response, Wash ington, DC. NTIS PB-86- 134699/AS.
van Rij, A.M., C.D. Thomson, J.M. McKenzie an d M.F. Robinson. 1979. Se lenium deficiency in total parenteral nutr ition. Am. J. Clin . Nutr. 32: 2076-2085.
Watrach, A.M., J.A. Milner, M.A. Watrach and K.A. Poirier. 1984. Inhibition of human breast cancer cells by selenium. Cancer Lett. 25: 41-47.
Weisberger, A.S. and L.G. Suhrland. 1956a. Studies on analogues of L- cystei ne and L-cystine. II. The effect of selenium cystine on Murphy lymphosarcoma tumor ce lls in the rat. Blood. 11: 11- 18.
Weisberger, A.S. and L.G. Suhrla nd. 1956b. Studies on analogues of L- cysteine and L-cystine. III. The effect of se lenium cystine on leukemia. Blood. 11: 19-30.
Whanger, P.D., M.A. Beilstein, C.D. Thomson, M.F. Robinson and M. Ho we. 1988. Blood selenium and glutathione peroxidase acti vity of populations in New Zealand, Oregon and South Dakota. FASEB J. 2(14): 2996-3002.
Yang, G., S. Wang, R. Zhou an d S. Sun. 1983. Endemic selenium intoxication of humans in China. Am. J. Clin . Nutr. 37: 872-881. 

### http://www.epa.gov/iris/subst/0472.htmYang, G., R. Zhou, S. Yin, et al. 1989a. Studies of safe maximal daily dietary selenium intake in a seleniferous area in China. I. Se lenium intake and tissue levels of the inhabitants. J. Trace Elem. Electrolytes Health Dis. 3(2): 77-87.
Yang, G., S. Yin, R. Zhou, et al. 1989b. Studies of safe maximal daily dietary Se-intake in a seleniferous area in China. II. Relation between Se- intake and the manifestation of clinical signs and certain biochemical al terations in blood and urine. J. Trac e Elem. Electrolytes Health Dis. 3 (2): 123-130.

_VI.B. Inhalation RfC References

None

_VI.C. CarcinogenicityAssessment References
Glover, J.R. 1970. Selenium and its industrial toxicology. In d. Med. Surg. 39(1): 26-30.
Harr, J.R., J.F. Bone, I.J. Tinsle y, P.H. Weswig and R.S. Yamamo to. 1967. Selenium toxicity in rats. II. Histopathology. In: Selenium in Biomedic ine, O.H. Muth, J.E. Ol dfield, P.H. Weswig, Ed. Proc. 1st Int. Symp., Oregon State University , 1966. AVI Publishing Co., Westport, Conn. p. 153- 178. (Cited in U.S. EPA, 1989)

Jansson, B., M.M. Jacobs and A.C. Griffin. 1978. Gastro intestinal cancer: Epidemiology and experimental studies. Adv. Exp. Med. Biol. 91: 305-322.
Kok, F.J., A.M. De Bruijn, A. Hofman, R. Vermeeren and H. A. Valkenburg. 1987. Is serum selenium a risk factor for cancer in men only? Am. J. Epidemiol. 125(1): 12-16.
Koller, L.D., J.H. Exon, P.A. Talcott, C.A. Osborne and G.M. Henningsen. 1986. Immune responses in rats supplemented with se lenium. Clin. Exp. Immunol. 63: 570-576.
Lofroth, G. and B.N. Ames. 1978. Mutagenici ty of inorganic compounds in Salmonella typhimurium: Arsenic, chromium and selenium. Mutat. Res. 53: 65-66.
Nakamuro, K., K. Yoshikawa, Y. Sayato, H. Kurata, M. Tonomura and A. Tonomura. 1976. Studies on selenium-related compounds. V. Cytogenetic ef fect and reactivity with DNA. Mutat. Res. 40: 177-184.
Nelson, A.A., O.G. Fitzhugh and H.O. Calvery. 1943. Liver tumors following cirrhosis caused by selenium in rats. Cancer Res. 3: 230-236. (Cited in U.S. EPA, 1989)
Newton, M.F. and L.J. Lilly. 1986. Tissue-specific clastogenic effe cts of chromium and selenium salts in vivo. Mutat. Res. 169: 61-69.
Noda, M., T. Takano and H. Sakurai. 1979. Muta genic activity of seleni um compounds. Mutat. Res. 66: 175-179.
Ray, J.H. and L.C. Altenburg. 1980. Dependenceof the sister-chromat id exchange-inducing abilities of inorganic selenium compounds on the valence state of selenium . Mutat. Res. 78: 261- 266. 

### http://www.epa.gov/iris/subst/0472.htmSalonen, J.T., G. Alfthan, J.K. Huttunen and P. Puska. 1984. Association between serum selenium and the risk of cancer. Am. J. Epidemiol. 120(3): 342-349. (Cited in U.S. EPA, 1989)
Schrauzer, G.N. and D. Ishmael. 1974. Effects of selenium and of arsenic on the genesis of spontaneous mammary tumors in inbred C3 H mice. Ann. Clin. Lab. Sci. 4: 441-447.
Schrauzer, G.N., D.A. Wh ite and C.J. Schneider. 1976. Inhibiti on of the genesi s of spontaneous mammary tumors in C3H mice: Effect of seleni um and of selenium-antagonistic elements and their possible role in human breastcancer. Bioinorg. Chem. 6: 265-270.
Schroeder, H.A. and M. Mitche ner. 1971. Selenium and tellurium in rats: Effect on growth, survival and tumors. J. Nutr. 101: 1531-1540.
Schroeder, H.A. and M. Mitche ner. 1972. Selenium and tellurium in mice: Effects on growth, survival and tumors. Arch. Environ. Health. 24: 66-71.
Shamberger, R.J. 1976. Selenium in health and disease. Proceedings of the Symposium on Selenium-Tellurium in the Environment. Industrial Health Foundation, Inc., Pittsburgh, PA. p. 253-267.
Shamberger, R.J. 1985. The genotoxicity of selenium. Mutat. Res. 154: 29-48. (Cited in U.S. EPA, 1989)
Shamberger, R.J. and D.V. Frost. 1969. Possible protective effect of selenium against human cancer. Can. Med. Assoc. J. 100: 682.
Shamberger, R.J. and C.E. Willis . 1971. Selenium distribution and human cancer mortality. Crit. Rev. Clin. Lab. Sci. 2: 211-221.
Shamberger, R.J., E. Rukovena, A. K. Longfield et al. 1973. Antioxid ants and cancer. I. Selenium in the blood of normals and cancer patien ts. J. Natl. Cancer Inst. 50(4): 863-870.
Tinsley, I.J., J.R. Harr, J.F. Bo ne, P.H. Weswig and R. S. Yamamoto. 1967. Se lenium toxicity in rats. I. Growth and longevity. In: Selenium in Bi omedicine, O.H. Muth, J.E. Oldfield, P.H. Weswig, Ed. Proc. 1st Int. Symp., Oregon State University, 1966. AVI Publis hing Co., Westport, Conn. p. 141-152. (Cited in U.S. EPA, 1989)
U.S. EPA. 1980. Ambient Water Quality Criteria fo r Selenium. Prepared by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Water Quality Pl anning and Standards, Washingt on, DC. EPA 440/5-80-070. NTIS PB 81-117814.

U.S. EPA. 1984. Health Effects Assessment for Selenium (a nd Compounds). Prepared by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH, for the Office of Emergency and Remedial Respon se, Washington, DC. EPA/540/1-86-058. NTIS PB 86-134699.

U.S. EPA. 1989. Health and En vironmental Effects Document for Selenium and Compounds. Prepared by the Office of Health and Environ mental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for the Offi ce of Solid Waste and Emergency Response, Washington, DC. 

### http://www.epa.gov/iris/subst/0472.htmDate Section Description Whiting, R.F., L. Wei and H. F. Stich. 1980. Unscheduled DN A synthesis and chromosome aberrations induced by inorganic and organic selenium compounds in the presence of glutathione. Mutat. Res. 78: 159-169.
Willett, W.C. and M.J. Stampfer. 1986. Selenium and huma n cancer. Acta Pharmacol. Toxicol. Suppl. 59: 240-247.
Willett, W.C., B.F. Polk, J.S. Morris et al. 1983. Prediagnostic serum selenium and risk of cancer. Lancet. 2: 130-134.
Yang, G., S. Wang, R. Zhou an d S. Sun. 1983. Endemic selenium intoxication of humans in China. Am. J. Clin . Nutr. 37: 872-881.



### _VII. Revision History
Substance Name — Selenium and Compounds CASRN — 7782-49-2

03/01/1991 II. Carcinogen icity assessment on-line 03/01/1991 VI. Bibliography on-line 06/01/1991 II.A.2. Para 4: Correct Sh amber&Willis to Shamberger&Willis 06/01/1991 I.A. Oral RfD summary on-line 06/01/1991 VI.A. Oral RfD references added 09/01/1991 I.A.2. Paragraph 2, line2: number corrected to 5/349 09/01/1991 I.A.3. Text revised 09/01/1991 I.A.5. Confidence in RfD changed; text revised 01/01/1992 IV. Regulatory Action section on-line 07/01/1993 II.D.3. Primary contact's phone number changed 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. 12/03/2002 I.A.6., II.D.2. Screening-Level Literature Review Findings message has been added.



### _VIII. Synonyms
Substance Name — Selenium and Compounds CASRN — 7782-49-2 Last Revised — 03/01/1991

• 7782-49-2 

### http://www.epa.gov/iris/subst/0472.htmIRIS Home Chronic HealthHazards for NonCarcinogenic Effects Reference Dose for Chronic Oral Exposure (RfD) • Oral RfD Summary • Selenium • C.I. 77805 • Caswell No. 732 • ELEMENTAL SELENIUM • EPA Pesticide Chemical Code 072001 • HSDB 4493 • SELEN [Polish] • Selenio [Spanish] • Selenium • SELENIUM ALLOY • SELENIUM BASE • SELENIUM DUST • SELENIUM ELEMENTAL • SELENIUM HOMOPOLYMER • UN 2658 • 13410-01-0 • Selenic acid, disodium salt • Caswell No. 791 • Disodium selenate • EPA Pesticide Chemical Code 072002 • Natriumseleniat [German] • NSC 378348 • Selenic acid, disodium salt • Sodium selenate • 10102-18-8 • Selenious acid, disodium salt • DISODIUM SELENITE • DISODIUM SELENIUM TRIOXIDE • HSDB 768 • Natriumselenit [German] • SELENIOUS ACID, DISODIUM SALT • SODIUM SELENITE • UN 2630 • 7783-00-8 • Selenious acid • HSDB 6065 • MONOHYDRATED SELENIUM DIOXIDE • Selenious Acid • 7783-08-6 • Selenic acid • Acide selenique [French] • Acido selenico [Spanish] • HSDB 675 • Selenic acid • UN 1905 • 1313-85-5 • Sodium selenide [Na2Se] • Disodium monoselenide • Sodium selenide 

### http://www.epa.gov/iris/subst/0472.htm• 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• 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 

### http://www.epa.gov/iris/subst/0472.htmCarcinogenic 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/0472.htm