United States
Environmental Protection
1=1 m m Agency
Provisional Peer-Reviewed Toxicity Values for
(CASRN 630-10-4)
Superfund Health Risk Technical Support Center
National Center for Environmental Assessment
Office of Research and Development
U.S. Environmental Protection Agency
Cincinnati, OH 45268

Commonly Used Abbreviations
Benchmark Dose
Integrated Risk Information System
inhalation unit risk
lowest-observed-adverse-effect level
LOAEL adjusted to continuous exposure duration
LOAEL adjusted for dosimetric differences across species to a human
no-ob served-adverse-effect level
NOAEL adjusted to continuous exposure duration
NOAEL adjusted for dosimetric differences across species to a human
no-ob served-effect level
oral slope factor
provisional inhalation unit risk
provisional oral slope factor
provisional inhalation reference concentration
provisional oral reference dose
inhalation reference concentration
oral reference dose
uncertainty factor
animal to human uncertainty factor
composite uncertainty factor
incomplete to complete database uncertainty factor
interhuman uncertainty factor
LOAEL to NOAEL uncertainty factor
subchronic to chronic uncertainty factor

On December 5, 2003, the U.S. Environmental Protection Agency's (U.S. EPA) Office of
Superfund Remediation and Technology Innovation (OSRTI) revised its hierarchy of human
health toxicity values for Superfund risk assessments, establishing the following three tiers as the
new hierarchy:
1)	U.S. EPA's Integrated Risk Information System (IRIS).
2)	Provisional Peer-Reviewed Toxicity Values (PPRTVs) used in U.S. EPA's Superfund
3)	Other (peer-reviewed) toxicity values, including
~	Minimal Risk Levels produced by the Agency for Toxic Substances and Disease
Registry (ATSDR),
~	California Environmental Protection Agency (CalEPA) values, and
~	EPA Health Effects Assessment Summary Table (HEAST) values.
A PPRTV is defined as a toxicity value derived for use in the Superfund Program when
such a value is not available in U.S. EPA's IRIS. PPRTVs are developed according to a Standard
Operating Procedure (SOP) and are derived after a review of the relevant scientific literature
using the same methods, sources of data, and Agency guidance for value derivation generally
used by the U.S. EPA IRIS Program. All provisional toxicity values receive internal review by
two U.S. EPA scientists and external peer review by three independently selected scientific
experts. PPRTVs differ from IRIS values in that PPRTVs do not receive the multiprogram
consensus review provided for IRIS values. This is because IRIS values are generally intended
to be used in all U.S. EPA programs, while PPRTVs are developed specifically for the Superfund
Because new information becomes available and scientific methods improve over time,
PPRTVs are reviewed on a 5-year basis and updated into the active database. Once an IRIS
value for a specific chemical becomes available for Agency review, the analogous PPRTV for
that same chemical is retired. It should also be noted that some PPRTV documents conclude that
a PPRTV cannot be derived based on inadequate data.
Users of this document should first check to see if any IRIS values exist for the chemical
of concern before proceeding to use a PPRTV. If no IRIS value is available, staff in the regional
Superfund and Resource Conservation and Recovery Act (RCRA) program offices are advised to
carefully review the information provided in this document to ensure that the PPRTVs used are
appropriate for the types of exposures and circumstances at the Superfund site or RCRA facility
in question. PPRTVs are periodically updated; therefore, users should ensure that the values
contained in the PPRTV are current at the time of use.
It is important to remember that a provisional value alone tells very little about the
adverse effects of a chemical or the quality of evidence on which the value is based. Therefore,

users are strongly encouraged to read the entire PPRTV document and understand the strengths
and limitations of the derived provisional values. PPRTVs are developed by the U.S. EPA
Office of Research and Development's National Center for Environmental Assessment,
Superfund Health Risk Technical Support Center for OSRTI. Other U.S. EPA programs or
external parties who may choose of their own initiative to use these PPRTVs are advised that
Superfund resources will not generally be used to respond to challenges of PPRTVs used in a
context outside of the Superfund Program.
Questions Regarding PPRTVs
Questions regarding the contents of the PPRTVs and their appropriate use (e.g., on
chemicals not covered, or whether chemicals have pending IRIS toxicity values) may be directed
to the U.S. EPA Office of Research and Development's National Center for Environmental
Assessment, Superfund Health Risk Technical Support Center (513-569-7300), or OSRTI.
Selenourea is an organic selenium compound with a molecular weight of 123.02 g/mol.
Figure 1 shows the chemical structure of selenourea. No reference dose (RfD) for selenourea is
currently available on IRIS (U.S. EPA, 2009) or the Drinking Water Standards and Health
Advisories list (U.S. EPA, 2006). The HEAST (U.S. EPA, 1997) reports both a subchronic and
chronic RfD of 0.005 mg/kg-day for selenourea. This RfD is derived from a
lowest-observed-adverse-effect level (LOAEL) of 3.2 mg/day based on selenosis, resulting from
selenium intake, observed in an epidemiology study (Yang et al., 1983). In this study, a human
population exposed to high levels of selenium in their diet exhibited signs of chronic selenosis
including loss of hair and nails, and lesions of the skin and nervous system. To derive this RfD,
the LOAEL of 3.2 mg/day for a 55-kg body weight man was converted to a daily dose of
0.06 mg/kg-day. An uncertainty factor (UF) of 10 was used to extrapolate from the LOAEL and
a modifying factor of 1.5 was used to account for differences in the absorption of selenium from
food and water. This assessment for selenourea, which had been on IRIS, was withdrawn in
1991, and is not currently referenced by any U.S. EPA document. This same RfD is currently
found in HEAST and on IRIS for "selenium and compounds," but it is based on a more recent
study by Yang et al. (1989) that identifies a LOAEL of 1.3 mg/day based on selenosis observed
in a human population. In deriving this RfD, a UF of 3 and a modifying factor of 1 were
employed. The fact that this same RfD has been used for both selenourea and selenium and
compounds suggests that the toxicity of these compounds is simply a reflection of the selenium
that they contain.
Figure 1. Chemical Structure of Selenourea

No inhalation reference concentration (RfC) or cancer assessment for selenourea is
available on IRIS (U.S. EPA, 2009) or in the HEAST (U.S. EPA, 1997). The chemical
assessments and related activities (CARA) lists (U.S. EPA, 1994, 1991) include no relevant
documents for selenourea. CalEPA (2009a, b), ATSDR (2009), and the World Health
Organization (WHO, 2009) have not evaluated the toxicity of selenourea. Occupational
exposure limits for selenourea have not been established by the American Conference of
Governmental Industrial Hygienists (ACGIH, 2008), the National Institute for Occupational
Safety and Health (NIOSH, 2009), or the Occupational Safety and Health Administration
(OSHA, 2009). Neither the International Agency for Research on Cancer (IARC, 2009) or the
National Toxicology Program (NTP, 2009, 2005) have evaluated the carcinogenicity of
For this PPRTV, literature searches were conducted from the 1960s through July 2009 for
studies relevant to provisional toxicity values for selenourea. The databases searched include
BIOSIS, and Current Contents (last 6 months).
Human Studies
There are no studies of the health effects of selenourea in humans exposed by any route
in the available literature.
Animal Studies
Oral Exposure
Dhillon et al. (1990) conducted two experiments to determine whether chronic selenosis
(via feeding of selenium-rich rice straw during the winter months) was the causative factor in a
disease (called Degnala disease) observed in cattle and buffalo in India. In a short-term
experiment, two buffalo calves (unspecified sex and breed) were administered selenourea (purity
not specified) at 0.3 mg/kg-day (in water). There was no control group. Animals were examined
daily for general condition, coat condition, leg coordination, appetite, rumen movements, and
body temperature (every 4th day); body weight was not measured. Both calves treated with
selenourea developed diarrhea by Day 5. One animal exhibited edema and redness on the tip of
the tail and weakness; this animal died on Day 7. The remaining animal had skin cracks and
edema in the fetlock region by Day 7 and died on Day 9. Gross postmortem evaluations revealed
mild congestion of the gastrointestinal tract, but no other abnormalities.
In the second experiment conducted by Dhillon et al. (1990), five buffalo calves (sex and
breed unspecified) were administered selenourea (purity not specified) at 0.15 mg/kg-day (in
water) for 75 days (Dhillon et al., 1990). One animal was not treated and served as a control.
Endpoints routinely evaluated throughout the study included general condition, coat condition,
leg coordination, appetite, rumen movements, feces consistency, and temperature; body weight,
however, was not measured. All calves survived for the duration of the experiment. At the
conclusion of the study, two treated animals were sacrificed and received postmortem
evaluation; the control animal was not examined. Histopathological examinations of the skin,

blood vessels, small intestine, heart, liver, and kidneys were performed on the sacrificed animals.
The remaining animals were observed for up to 120 days; however, the study authors did not
report the calves' ultimate disposition.
Clinical signs observed in treated animals include edema, hair loss, skin cracks, and
wounds of the fetlock region; hoof cracks; tail edema and necrosis; ear tip necrosis; and hoof
rings. Appetite and body temperature were not affected. Postmortem evaluation of two animals
sacrificed at 75 days revealed mild congestion of the gastrointestinal tract and petechial
hemorrhages on the epicardium. Histopathological analysis indicated necrosis of the epidermis;
infiltration of the dermal epithelium with mononuclear cells, neutrophils, and eosinophils; and
proliferation of fibrous tissue (location or nature of fibrous tissue was not specified). Thrombus
formation in blood vessels was apparent. Degenerative changes were seen in hepatocytes, the
walls of blood vessels, and the tubular epithelium of the kidney. In the liver, the central vein was
observed to be dilated, and the portal triad had mild leukocytic infiltration. Dhillon et al. (1990)
did not specify whether these effects occurred in one or both of the sacrificed animals, and there
was no histopathologic evaluation in the control animal. The only selenourea dose tested in this
study (0.15 mg/kg-day) may be considered a LOAEL based on clinical signs and possible effects
on the blood vessels, kidney, and liver in buffalo calves. However, as there was no gross or
microscopic postmortem evaluation of the control animal, the microscopic changes in the blood
vessels, kidneys, and liver cannot be clearly attributed to selenourea treatment.
In a second subchronic study of buffalo calves, by Deore et al., 2002, selenourea was
repeatedly administered to buffalo calves (3/dose of unspecified sex) in drinking water at 0 or
0.3 mg/kg-day for 75 days. Calves were evaluated daily for physical appearance, posture, gait,
skin luster, temperature, and the appearance of toxic effects; body weight was not measured.
Blood and hair samples were collected from the calves before the start of the experiment (Day 0)
and at regular intervals for the duration of the experiment for analysis of selenium levels. The
animals were not subjected to gross or microscopic examination at the end of the study. No
animals died during the course of the experiment. Clinical signs in the form of redness of the
eyes and lacrimation first appeared within 6-8 days in the treated animals. Other clinical signs
observed as the study progressed included alopecia, skin cracks, ridges and rings on hooves,
dried and curved ear tips, and hoof elongation. As shown in Table 1, the activity of erythrocytic
glutathione peroxidase increased significantly over preexposure levels by Week 5, and it was
increased more than 3-fold by the final week of the study. Hair selenium levels were
significantly increased compared to the preexposure level after 4 weeks of selenourea
administration, reaching a peak of 22.91 ppm by Week 11 (see Table 1). From Day 6 onward,
blood selenium levels in treated animals were statistically significantly (p < 0.05) elevated
compared to the preexposure level of 0.70 jag/mL; blood levels peaked at 3.12 jag/mL on Day 75
(see Table 1). The study authors reported that clinical signs of chronic selenosis appeared when
blood selenium reached a concentration of about 2.0 |ig/mL, and that these signs became
prominent at selenium concentrations >2.5 |ig/mL. This study identifies a freestanding LOAEL
of 0.3 mg/kg-day based on clinical signs of toxicity in buffalo calves.

Table 1. Significant Changes in Buffalo Calves Given Selenourea Orally for 75 Days3
0.3 mg/kg-day
(Day 0)
Terminal level
(Day 75)
(Day 0)
Terminal level
(Day 75)
Blood selenium (ng/mL)b
0.78 ±0.05
0.77 ± 0.02
0.70 ±0.08
3.12 ± 0.01°
Hair selenium (ppm)b
2.94 ±0.55
3.04 ±0.47
2.42 ±0.60
22.91 ±2.6C
Erythrocyte glutathione peroxidase
activity (EU/mg Hb)b
6.21 ± 1.4
6.24 ± 1.39
5.35 ±0.94
18.81 ±0.46c
aDeore et al. (2002).
Values presented are means ± standard error.
°Significantly different from preexposure control (p < 0.01).
Inhalation Exposure
No inhalation studies of selenourea were located.
Other Studies
Deore et al., 2007 administered selenourea via gavage or intravenously at 0.75 mg/kg and
followed for up to 48 hours after treatment to buffalo calves (three/group of unspecified sex).
Selenium concentrations in blood and urine were measured spectrophotometrically in samples
taken at intervals up to 48 hours after selenourea administration. Plots of blood concentrations of
selenium over time following intravenous or oral dose of selenourea each showed two distinct
peaks: Blood selenium levels averaged 3.59 [j,g/mL 1 minute after intravenous injection,
declined to 0.34 [j,g/mL by 4 hours, and peaked again at 6 hours to 2.31 |ig/mL. After oral
dosing, an initial blood peak of 1.56 [j,g/mL was observed at 2 hours, followed by a decline for
the next 4 hours and a second peak of 1.05 [j,g/mL at 8 hours. Oral administration of selenourea
resulted in a lower area under the blood-time concentration curve (AUC) than intravenous
administration (18.46 [j,g/hour/mL after oral dosing vs. 23.97 [j,g/hour/mL after intravenous
dosing), but it had a longer mean residence time and elimination half-life and a larger
steady-state volume of distribution. The oral bioavailability of selenium following selenourea
treatment, calculated as the oral intravenous ratio of AUCs, was estimated to be 77%. More
selenium was excreted in the urine of calves treated intravenously than orally (22% total dose
excreted by 24 hours after intravenous dosing vs. 5.9% after oral dosing).
In another toxicokinetic study, Cummins and Kimura (1971) administered oral doses of
selenourea and several other selenium compounds (biphenyl selenium, sodium selenite, selenium
sulfide, and elemental selenium, each at a dose equivalent to 2.0 mg selenium/kg body weight) to
groups of two male mongrel dogs and collected blood samples at intervals up to 32 hours after
dosing. Blood samples were analyzed for selenium content. Administration of selenourea
resulted in a peak blood concentration of 0.6 |ig selenium/mL blood (average for the two dogs,
estimated from data presented graphically). The study authors reported that peak selenium blood
concentration was positively correlated with toxicity (as measured by LD50 in rats) for all
selenium compounds tested—except biphenyl selenium (which resulted in high selenium blood
concentrations, but low toxicity); the more toxic sodium selenite resulted in a peak blood
selenium concentration of approximately 1.0 |ig/mL, while the less toxic selenium sulfide and
elemental selenium resulted in slightly lower peak selenium blood levels of about 0.5 and
0.3 |ig/mL, respectively.

Two studies examined the tissue distribution of radiolabeled selenourea (75Se)
administered via injection. Breccia et al. (1966) observed the highest radioactivity in the liver,
kidney, and spleen of rats treated via intraperitoneal injection, while Carr and Walker (1964)
reported the highest radioactivity in the liver, kidney, and lung of rabbits treated via intravenous
In an acute lethality study, Cummins and Kimura (1971) treated Sprague-Dawley rats
(six/dose of unspecified sex) with selenourea and several other selenium compounds via gavage
at unspecified doses and followed for 7-10 days after treatment. The study authors reported an
LD50 of 50 mg/kg (95% confidence interval, 35.7-70 mg/kg) for selenourea. Other selenium
compounds exhibited a wide range of LD50 values in rats that ranged from 7 mg/kg (for sodium
selenite) up to 6,700 mg/kg (for elemental selenium).
Other Routes of Exposure
Badiello et al. (1967) administered a single intraperitoneal injection of selenourea at 0,
0.4, 0.8, 1.6, or 3.0 mg (approximately 3, 5, 11, or 20 mg/kg body weight based on the reported
average weight) to Wistar rats (eight males/dose, weighing an average of 150 g) and observed up
to 3 months following treatment. Clinical signs were monitored throughout the study and
hematological parameters (granulocyte and lymphocyte counts) were measured for the first
6 days. None of the rats administered 0.4 or 0.8 mg selenourea died, and the study authors noted
no changes in physiological activity. Plots of lymphocyte and granulocyte counts over time
showed an increase in granulocytes and a decrease in lymphocytes in rats given 0.8 mg
selenourea 6-12 hours after treatment (data shown for this treatment group only); both cell
counts were comparable to controls thereafter. Rats treated with 1.6 mg selenourea exhibited
sluggishness and a diminished appetite. One rat in this group died; however, the study authors
indicated that no macroscopic visceral changes were apparent. In the 3.0-mg treatment group,
one rat died after 48 hours on study. Surviving rats in this dose group exhibited marked
sluggishness, alopecia, total paralysis of the hind legs, and anorexia with a marked loss in body
weight and accompanying cachexia (physical wasting).
Because of the lack of human oral data and the inadequacy of the animal oral data,
provisional RfD values for selenourea cannot be derived. Oral data for selenourea are limited to
two subchronic studies in which selenourea was administered to buffalo calves
(Deore et al., 2002; Dhillon et al., 1990). Buffalo calves were tested because the studies were
initially designed to determine whether chronic selenosis was the causative factor in a disease
(called Degnala disease) observed in cattle and buffalo in India (Dhillon et al., 1990). Neither of
these studies is useful for dose-response assessment because of the atypical animal model
employed, as well as other study limitations, as follows: the sample sizes in both studies were
very small (three to five animals/dose group). The study by Dhillon et al. (1990) includes only
one control animal, and did not conduct any gross or microscopic postmortem examination of
this animal. In the study by Deore et al. (2002), the toxicological evaluations were limited to
clinical signs of toxicity and glutathione peroxidase activity. Finally, each study assessed the

toxicity of selenourea at only a single dose level—and neither study identified a
no-observed-adverse-effect level (NOAEL).
Because of the lack of human or animal inhalation data, provisional RfC values for
selenourea cannot be derived
Weight-of-Evidence Descriptor
Under the 2005 Guidelines for Carcinogen Risk Assessment (U.S. EPA, 2005), there is
"Inadequate Information to Assess the Carcinogenic Potential" of Selenourea. There are no
human or animal studies of the potential carcinogenicity of selenourea via any route, and
selenourea has not been tested for genotoxicity.
Quantitative Estimates of Carcinogenic Risk
The lack of available data precludes derivation of quantitative estimates (i.e., p-OSF and
p-IUR) of cancer risk for selenourea.
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