TOXICOLOGICAL PROFILE FOR 

SELENIUM 

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES 

Public Health Service 

Agency for Toxic Substances and Disease Registry
 

September 2003 
SELENIUM ii 

DISCLAIMER 

The use of company or product name(s) is for identification only and does not imply endorsement by the 

Agency for Toxic Substances and Disease Registry. 
SELENIUM iii 

UPDATE STATEMENT 

A Toxicological Profile for selenium, Draft for Public Comment was released in September, 2001. This 

edition supersedes any previously released draft or final profile. 

Toxicological profiles are revised and republished as necessary, but no less than once every three years. 

For information regarding the update status of previously released profiles, contact ATSDR at: 

Agency for Toxic Substances and Disease Registry
 

Division of Toxicology/Toxicology Information Branch 

1600 Clifton Road NE, 

Mailstop E-29 

Atlanta, Georgia 30333 



SELENIUM vii 

QUICK REFERENCE FOR HEALTH CARE PROVIDERS 

Toxicological Profiles are a unique compilation of toxicological information on a given hazardous 

substance. Each profile reflects a comprehensive and extensive evaluation, summary, and interpretation 

of available toxicologic and epidemiologic information on a substance. Health care providers treating 

patients potentially exposed to hazardous substances will find the following information helpful for fast 

answers to often-asked questions. 

Primary Chapters/Sections of Interest 

Chapter 1: Public Health Statement: The Public Health Statement can be a useful tool for educating 

patients about possible exposure to a hazardous substance. It explains a substance’s relevant 

toxicologic properties in a nontechnical, question-and-answer format, and it includes a review of 

the general health effects observed following exposure. 

Chapter 2: Relevance to Public Health: The Relevance to Public Health Section evaluates, interprets, 

and assesses the significance of toxicity data to human health. 

Chapter 3: Health Effects: Specific health effects of a given hazardous compound are reported by type 

of health effect (death, systemic, immunologic, reproductive), by route of exposure, and by length 

of exposure (acute, intermediate, and chronic). In addition, both human and animal studies are 

reported in this section. 

NOTE: Not all health effects reported in this section are necessarily observed in the clinical 

setting. Please refer to the Public Health Statement to identify general health effects 

observed following exposure. 

Pediatrics: Four new sections have been added to each Toxicological Profile to address child health 

issues: 

Section 1.6 How Can (Chemical X) Affect Children? 

Section 1.7 How Can Families Reduce the Risk of Exposure to (Chemical X)? 

Section 3.7 Children’s Susceptibility 

Section 6.6 Exposures of Children 

Other Sections of Interest: 

Section 3.8 Biomarkers of Exposure and Effect 

Section 3.11 Methods for Reducing Toxic Effects 

ATSDR Information Center 

Phone: 1-888-42-ATSDR or (404) 498-0110 Fax: (404) 498-0093 

E-mail: atsdric@cdc.gov Internet: http://www.atsdr.cdc.gov 

The following additional material can be ordered through the ATSDR Information Center: 

Case Studies in Environmental Medicine: Taking an Exposure History—The importance of taking an 

exposure history and how to conduct one are described, and an example of a thorough exposure 

history is provided. Other case studies of interest include Reproductive and Developmental 

Hazards; Skin Lesions and Environmental Exposures; Cholinesterase-Inhibiting Pesticide 

Toxicity; and numerous chemical-specific case studies. 
SELENIUM viii 

Managing Hazardous Materials Incidents is a three-volume set of recommendations for on-scene 

(prehospital) and hospital medical management of patients exposed during a hazardous materials 

incident. Volumes I and II are planning guides to assist first responders and hospital emergency 

department personnel in planning for incidents that involve hazardous materials. Volume III— 

Medical Management Guidelines for Acute Chemical Exposures—is a guide for health care 

professionals treating patients exposed to hazardous materials. 

Fact Sheets (ToxFAQs) provide answers to frequently asked questions about toxic substances. 

Other Agencies and Organizations 

The National Center for Environmental Health (NCEH) focuses on preventing or controlling disease, 

injury, and disability related to the interactions between people and their environment outside the 

workplace. Contact: NCEH, Mailstop F-29, 4770 Buford Highway, NE, Atlanta, GA 30341­

3724 • Phone: 770-488-7000 • FAX: 770-488-7015. 

The National Institute for Occupational Safety and Health (NIOSH) conducts research on occupational 

diseases and injuries, responds to requests for assistance by investigating problems of health and 

safety in the workplace, recommends standards to the Occupational Safety and Health 

Administration (OSHA) and the Mine Safety and Health Administration (MSHA), and trains 

professionals in occupational safety and health. Contact: NIOSH, 200 Independence Avenue, 

SW, Washington, DC 20201 • Phone: 800-356-4674 or NIOSH Technical Information Branch, 

Robert A. Taft Laboratory, Mailstop C-19, 4676 Columbia Parkway, Cincinnati, OH 45226-1998 

• Phone: 800-35-NIOSH. 

The National Institute of Environmental Health Sciences (NIEHS) is the principal federal agency 

for biomedical research on the effects of chemical, physical, and biologic environmental 

agents on human health and well-being. Contact: NIEHS, PO Box 12233, 104 T.W. 

Alexander Drive, Research Triangle Park, NC 27709 • Phone: 919-541-3212. 

Referrals 

The Association of Occupational and Environmental Clinics (AOEC) has developed a network of clinics 

in the United States to provide expertise in occupational and environmental issues. Contact: 

AOEC, 1010 Vermont Avenue, NW, #513, Washington, DC 20005 • Phone: 202-347-4976 • 

FAX: 202-347-4950 • e-mail: AOEC@AOEC.ORG • Web Page: http://www.aoec.org/. 

The American College of Occupational and Environmental Medicine (ACOEM) is an association of 

physicians and other health care providers specializing in the field of occupational and 

environmental medicine. Contact: ACOEM, 55 West Seegers Road, Arlington Heights, IL 

60005 • Phone: 847-818-1800 • FAX: 847-818-9266. 
SELENIUM ix 

CONTRIBUTORS 

CHEMICAL MANAGER(S)/AUTHOR(S): 

John Risher, Ph.D. 

ATSDR, Division of Toxicology, Atlanta, GA 

A. Rosa McDonald, Ph.D. 

Mario J. Citra, Ph.D. 

Stephen Bosch, B.S. 

Richard J. Amata, M.S. 

Syracuse Research Corporation, North Syracuse, NY 

THE PROFILE HAS UNDERGONE THE FOLLOWING ATSDR INTERNAL REVIEWS: 

1. Health Effects Review. The Health Effects Review Committee examines the health effects 

chapter of each profile for consistency and accuracy in interpreting health effects and classifying 

end points. 

2.	 Minimal Risk Level Review. The Minimal Risk Level Workgroup considers issues relevant to 

substance-specific minimal risk levels (MRLs), reviews the health effects database of each 

profile, and makes recommendations for derivation of MRLs. 

3. Data Needs Review. The Research Implementation Branch reviews data needs sections to assure 

consistency across profiles and adherence to instructions in the Guidance. 

SELENIUM xi 

PEER REVIEW 

A peer review panel was assembled for selenium. The panel consisted of the following members: 

1. Orville Levander, Ph.D., Silver Springs, Maryland 

2. Gregory Möller, Ph.D., Associate Professor of Environmental Chemistry and Toxicology, Moscow, 

Indiana 

3. Raghubir Sharma, Ph.D., D.V.M., Professor of Physiology and Pharmacology, Athens, Georgia 

These experts collectively have knowledge of selenium's physical and chemical properties, toxicokinetics, 

key health end points, mechanisms of action, human and animal exposure, and quantification of risk to 

humans. All reviewers were selected in conformity with the conditions for peer review specified in 

Section 104(I)(13) of the Comprehensive Environmental Response, Compensation, and Liability Act, as 

amended. 

Scientists from the Agency for Toxic Substances and Disease Registry (ATSDR) have reviewed the peer 

reviewers' comments and determined which comments will be included in the profile. A listing of the 

peer reviewers' comments not incorporated in the profile, with a brief explanation of the rationale for their 

exclusion, exists as part of the administrative record for this compound. A list of databases reviewed and 

a list of unpublished documents cited are also included in the administrative record. 

The citation of the peer review panel should not be understood to imply its approval of the profile's final 

content. The responsibility for the content of this profile lies with the ATSDR. 

SELENIUM xiii 

CONTENTS 

FOREWORD ................................................................................................................................................v 

CONTRIBUTORS.......................................................................................................................................ix 

PEER REVIEW ...........................................................................................................................................xi 

LIST OF FIGURES ..................................................................................................................................xvii 

LIST OF TABLES.....................................................................................................................................xix 

1. PUBLIC HEALTH STATEMENT..........................................................................................................1 

1.1 WHAT IS SELENIUM?..............................................................................................................1 

1.2 WHAT HAPPENS TO SELENIUM WHEN IT ENTERS THE ENVIRONMENT? ................2 

1.3 HOW MIGHT I BE EXPOSED TO SELENIUM?.....................................................................3 

1.4 HOW CAN SELENIUM ENTER AND LEAVE MY BODY? ..................................................3 

1.5 HOW CAN SELENIUM AFFECT MY HEALTH? ...................................................................4 

1.6 HOW CAN SELENIUM AFFECT CHILDREN? ......................................................................7 

1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO SELENIUM? ..................8 

1.8 IS THERE A MEDICAL TEST TO DETERMINE WHETHER I HAVE BEEN EXPOSED 

TO SELENIUM?.......................................................................................................................................9 

1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO 

PROTECT HUMAN HEALTH? ............................................................................................................10 

1.10 WHERE CAN I GET MORE INFORMATION? .....................................................................11 

2. RELEVANCE TO PUBLIC HEALTH .................................................................................................13 

2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO SELENIUM IN THE 

UNITED STATES ..................................................................................................................................13 

2.2 SUMMARY OF HEALTH EFFECTS......................................................................................13 

2.3 MINIMAL RISK LEVELS (MRLs) .........................................................................................20 

3. HEALTH EFFECTS..............................................................................................................................23 

3.1 INTRODUCTION.....................................................................................................................23 

3.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE ..................................24 

3.2.1 Inhalation Exposure ..............................................................................................................26 

3.2.1.1 Death.................................................................................................................................26 

3.2.1.2 Systemic Effects ...............................................................................................................31 

3.2.1.3 Immunological and Lymphoreticular Effects...................................................................36 

3.2.1.4 Neurological Effects .........................................................................................................36 

3.2.1.5 Reproductive Effects.........................................................................................................37 

3.2.1.6 Developmental Effects......................................................................................................37 

3.2.1.7 Cancer...............................................................................................................................37 

3.2.2 Oral Exposure........................................................................................................................37 

3.2.2.1 Death.................................................................................................................................79 

3.2.2.2 Systemic Effects ...............................................................................................................82 

3.2.2.3 Immunological and Lymphoreticular Effects.................................................................102 

3.2.2.4 Neurological Effects.......................................................................................................106 

3.2.2.4 Reproductive Effects.......................................................................................................110 
SELENIUM xiv 

3.2.2.6 Developmental Effects....................................................................................................114 

3.2.2.7 Cancer.............................................................................................................................117 

3.2.3 Dermal Exposure.................................................................................................................125 

3.2.3.1 Death...............................................................................................................................125 

3.2.3.2 Systemic Effects .............................................................................................................125 

3.2.3.3 Immunological and Lymphoreticular Effects.................................................................126 

3.2.3.4 Neurological Effects.......................................................................................................127 

3.2.3.5 Reproductive Effects.......................................................................................................127 

3.2.3.6 Developmental Effects....................................................................................................127 

3.2.3.7 Cancer.............................................................................................................................127 

3.2.4 Other Routes of Exposure ...................................................................................................128 

3.3 GENOTOXICITY ...................................................................................................................129 

3.4 TOXICOKINETICS................................................................................................................135 

3.4.1 Absorption...........................................................................................................................136 

3.4.1.1 Inhalation Exposure ........................................................................................................136 

3.4.1.2 Oral Exposure .................................................................................................................143 

3.4.1.3 Dermal Exposure ............................................................................................................145 

3.4.2 Distribution .........................................................................................................................146 

3.4.2.1 Inhalation Exposure ........................................................................................................147 

3.4.2.2 Oral Exposure .................................................................................................................147 

3.4.2.3 Dermal Exposure ............................................................................................................150 

3.4.2.4 Other Routes of Exposure............................................................................................... 150 

3.4.3 Metabolism..........................................................................................................................151 

3.4.4 Elimination and Excretion...................................................................................................158 

3.4.4.1 Inhalation Exposure ........................................................................................................158 

3.4.4.2 Oral Exposure .................................................................................................................158 

3.4.4.3 Dermal Exposure ............................................................................................................162 

3.4.4.4 Other Routes of Exposure............................................................................................... 162 

3.4.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models ........... 163 

3.5 MECHANISMS OF ACTION ................................................................................................170 

3.5.1 Pharmacokinetic Mechanisms.............................................................................................170 

3.5.2 Mechanisms of Toxicity......................................................................................................172 

3.5.3 Animal-to-Human Extrapolations.......................................................................................175 

3.6 TOXICITIES MEDIATED THROUGH THE NEUROENDOCRINE AXIS ........................176 

3.7 CHILDREN’S SUSCEPTIBILITY.........................................................................................179 

3.8 BIOMARKERS OF EXPOSURE AND EFFECT..............................................................182 

3.8.1 Biomarkers Used to Identify or Quantify Exposure to Selenium ...................................183 

3.8.2 Biomarkers Used to Characterize Effects Caused by Selenium..........................................187 

3.9 INTERACTIONS WITH OTHER CHEMICALS ..................................................................188 

3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE.............................................192 

3.11 METHODS FOR REDUCING TOXIC EFFECTS.................................................................193 

3.11.1 Reducing Peak Absorption Following Exposure ................................................................194 

3.11.2 Reducing Body Burden .......................................................................................................194 

3.11.3 Interfering with the Mechanism of Action for Toxic Effects..............................................195 

3.12 ADEQUACY OF THE DATABASE......................................................................................196 

3.12.1 Existing Information on Health Effects of Selenium ..........................................................196 

3.12.2 Identification of Data Needs ...............................................................................................199 

3.12.3 Ongoing Studies ..................................................................................................................208 

4. CHEMICAL AND PHYSICAL INFORMATION..............................................................................217 

4.1 CHEMICAL IDENTITY......................................................................................................... 217 
SELENIUM xv 

4.2 PHYSICAL AND CHEMICAL PROPERTIES......................................................................217 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL..........................................................229 

5.1 PRODUCTION .......................................................................................................................229 

5.2 IMPORT/EXPORT .................................................................................................................230 

5.3 USE..........................................................................................................................................230 

5.4 DISPOSAL..............................................................................................................................234 

6. POTENTIAL FOR HUMAN EXPOSURE .........................................................................................235 

6.1 OVERVIEW............................................................................................................................235 

6.2 RELEASES TO THE ENVIRONMENT................................................................................237 

6.2.1 Air .......................................................................................................................................237 

6.2.2 Water...................................................................................................................................242 

6.2.3 Soil ......................................................................................................................................243 

6.3 ENVIRONMENTAL FATE....................................................................................................243 

6.3.1 Transport and Partitioning...................................................................................................243 

6.3.2 Transformation and Degradation ........................................................................................246
 

6.3.2.1 Air...................................................................................................................................246 

6.3.2.2 Water...............................................................................................................................247 

6.3.2.3 Sediment and Soil ...........................................................................................................248 

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT...............................249 

6.4.1 Air .......................................................................................................................................249 

6.4.2 Water...................................................................................................................................250 

6.4.3 Sediment and Soil ...............................................................................................................251 

6.4.4 Other Environmental Media................................................................................................252 

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE .....................................275 

6.6 EXPOSURES OF CHILDREN...............................................................................................279 

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES ...........................................280 

6.8 ADEQUACY OF THE DATABASE......................................................................................281 

6.8.1 Identification of Data Needs ...............................................................................................282 

6.8.2 Ongoing Studies ..................................................................................................................285 

7. ANALYTICAL METHODS ...............................................................................................................287 

7.1 BIOLOGICAL MATERIALS.................................................................................................287 

7.2 ENVIRONMENTAL SAMPLES............................................................................................297 

7.3 ADEQUACY OF THE DATABASE......................................................................................299 

7.3.1 Identification of Data Needs ...............................................................................................299 

7.3.2 Ongoing Studies ..................................................................................................................301 

8. REGULATIONS AND ADVISORIES ...............................................................................................303 

9. REFERENCES ....................................................................................................................................315 

10. GLOSSARY ......................................................................................................................................413 
SELENIUM xvi 

APPENDICES 

A. ATSDR MINIMAL RISK LEVELS AND WORKSHEETS....................................................A-1 

B. USER’S GUIDE........................................................................................................................ B-1 

C. ACRONYMS, ABBREVIATIONS, AND SYMBOLS............................................................ C-1 
SELENIUM xvii 

LIST OF FIGURES 

3-1. Levels of Significant Exposure to Selenium—Inhalation.............................................................30 

3-2. Levels of Significant Exposure to Selenium—Oral......................................................................64 

3-3. Levels of Significant Exposure to Selenium Sulfides—Oral........................................................75 

3-4. Metabolic Pathways for Selenium ..............................................................................................152 

3-5. Proposed Pathway for Formation of Dimethyl Selenide from Selenite in Animals ...................157 

3-6. Activation and Reduction of Selenate to Selenite in Yeast Saccharomyces cerevisiae..............159 

3-7. Conceptual Representation of a Physiologically Based Pharmacokinetic (PBPK) Model for a 

Hypothetical Chemical Substance ..............................................................................................165 

3-8. Selenite Model, a Kinetic Model for Selenite Metabolism.........................................................167 

3-9. Selenomethionine Model, a Kinetic Model for Selenomethionine Metabolism.........................169 

3-10. Existing Information on Health Effects of Selenium..................................................................197 

6-1. Frequency of NPL Sites with Selenium Contamination .............................................................236 

SELENIUM xix 

LIST OF TABLES 

3-1. Levels of Significant Exposure to Selenium—Inhalation.............................................................27
 

3-2. Levels of Significant Exposure to Selenium—Oral......................................................................38 

3-3. Levels of Significant Exposure to Selenium Sulfides—Oral........................................................71 

3-4. Genotoxicity of Selenium In Vitro..............................................................................................130
 

3-5. Genotoxicity of Selenium In Vivo...............................................................................................132 

3-6. Selenium Concentrations in Human Tissues ..............................................................................137 

3-7. Biomarkers: Selenium Concentrations in Human Tissues and Fluids........................................140 

3-8. On-going Studies on Selenium Health Effects ...........................................................................209 

4-1. Chemical Identity of Selenium and Selected Compounds..........................................................218 

4-2. Physical and Chemical Properties of Selenium and Selenium Compounds ...............................222 

5-1. Facilities that Produce, Process, or Use Selenium......................................................................231 

5-2. Facilities that Produce, Process, or Use Selenium Compounds..................................................232 

5-3. Some Selenium Compounds and Their Uses..............................................................................233 

6-1. Releases to the Environment from Facilities that Produce, Process, or Use Selenium...............238 

6-2. Releases to the Environment from Facilities that Produce, Process, or Use Selenium

 Compounds .................................................................................................................................239 

6-3. Selenium Concentrations in Foods in the United States .............................................................254 

6-4. U.S. Food and Drug Administration—Total Diet Study (TDS)—Market Baskets 91-3 

 through 99-1................................................................................................................................256 

6-5. Selenium Dietary Intake (μg/day) by Sex and Age for the Total U.S. Population, 1988–94 .....276 

6-6. Serum Selenium Concentrations (μg/L) in U.S. Population from NHANES III ........................278 

6-7. Ongoing Studies on Selenium.....................................................................................................286 

7-1. Analytical Methods for Determining Selenium in Biological Materials ....................................288 

7-2. Analytical Methods for Determining Selenium in Environmental Samples...............................290 

8-1. Regulations and Guidelines Applicable to Selenium..................................................................304 
SELENIUM xx 
SELENIUM 1 

1. PUBLIC HEALTH STATEMENT 

This public health statement tells you about selenium and the effects of exposure. 

The Environmental Protection Agency (EPA) identifies the most serious hazardous waste sites in 

the nation. These sites make up the National Priorities List (NPL) and are the sites targeted for 

long-term federal cleanup activities. Selenium has been found in at least 508 of the 1,623 current 

or former NPL sites. However, the total number of NPL sites evaluated for selenium is not 

known. As more sites are evaluated, the sites at which selenium is found may increase. This 

information is important because exposure to selenium at high levels may harm you and because 

these sites may be sources of exposure. A minimum dietary level of selenium is required for 

good health. 

When a substance is released from a large area, such as an industrial plant, or from a container, 

such as a drum or bottle, it enters the environment. This release does not always lead to 

exposure. You are exposed to a substance only when you come in contact with it. You may be 

exposed by breathing, eating, or drinking the substance, or by skin contact. 

If you are exposed to selenium, many factors determine whether you'll be harmed. These factors 

include the dose (how much), the duration (how long), and how you come in contact with 

it/them. You must also consider the other chemicals you're exposed to and your age, sex, diet, 

family traits, lifestyle, and state of health. 

1.1 WHAT IS SELENIUM? 

Selenium is a naturally occurring, solid substance that is widely but unevenly distributed in the 

earth's crust. It is also commonly found in rocks and soil. Selenium, in its pure form of metallic 

gray to black crystals, is often referred to as elemental selenium or selenium dust. Elemental 

selenium is commercially produced, primarily as a by-product of copper refining. Selenium is 

not often found in the environment in its elemental form, but is usually combined with other 
SELENIUM 2 

1. PUBLIC HEALTH STATEMENT 

substances. Much of the selenium in rocks is combined with sulfide minerals or with silver, 

copper, lead, and nickel minerals. Selenium also combines with oxygen to form several 

substances that are white or colorless crystals. Some selenium compounds are gases. Selenium 

and its compounds are used in some photographic devices, gun bluing (a liquid solution used to 

clean the metal parts of a gun), plastics, paints, anti-dandruff shampoos, vitamin and mineral 

supplements, fungicides, and certain types of glass. For example, selenium sulfide is used in 

anti-dandruff shampoos by the common trade name Selsun Blue. Selenium is also used to 

prepare drugs and as a nutritional feed supplement for poultry and livestock. More information 

on the chemical and physical properties, production, and uses of selenium are found in 

Chapters 4 and 5. 

1.2 WHAT HAPPENS TO SELENIUM WHEN IT ENTERS THE ENVIRONMENT? 

Selenium occurs naturally in the environment. As an element, selenium cannot be created or 

destroyed, although selenium can change forms in the environment. Weathering of rocks and 

soils may result in low levels of selenium in water, which may be taken up by plants. 

Weathering also releases selenium into the air on fine dust-like particles. Volcanic eruptions 

may release selenium in air. Selenium commonly enters the air from burning coal or oil. 

Selenium that may be present in fossil fuels combines with oxygen when burned, which may 

then react with water to form soluble selenium compounds. Airborne particles of selenium, such 

as in ash, can settle on soil or surface water. Disposal of selenium in commercial products and 

waste could also increase the amount of selenium in soil. The forms and fate of selenium in soil 

depend largely on the acidity of the surroundings and its interaction with oxygen. In the absence 

of oxygen when the soil is acidic, the amount of selenium that can enter plants and organisms 

should be low. Elemental selenium that cannot dissolve in water and other insoluble forms of 

selenium are less mobile and will usually remain in the soil, posing smaller risk of exposure. 

Selenium compounds that can dissolve in water are sometimes very mobile. Thus, there is an 

increased chance of exposure to these compounds. Selenium may enter surface water in 

irrigation drainage waters. Some evidence indicates that selenium can be taken up in tissues of 

aquatic organisms and possibly increase in concentration as the selenium is passed up through 

the food chain. Selenium concentrations in aquatic organisms have been a problem as a result of 
SELENIUM 3 

1. PUBLIC HEALTH STATEMENT 

irrigation runoff in some dry areas of the United States. Chapter 6 contains more information on 

what happens to selenium in the environment. 

1.3 HOW MIGHT I BE EXPOSED TO SELENIUM? 

People are exposed to low levels of selenium daily through food, water, and air. Selenium is also 

an essential nutrient for humans and animals. However, selenium can be harmful when regularly 

taken in amounts higher than those needed for good health. People receive the majority of their 

daily intake of selenium from eating food, and to a lesser extent, from water intake. Estimates of 

the average intake of selenium from food for the U.S. population range from 71 to 152 millionths 

of a gram of selenium per person per day. Low levels of selenium can also be found in drinking 

water. Selenium levels are less than 10 parts of selenium in a billion parts of water (10 ppb) in 

99.5% of drinking water sources tested. People may be exposed to higher-than-normal levels of 

selenium at hazardous waste sites by swallowing soil or water, or by breathing dust. In some 

parts of the United States, especially in the western states, some soils naturally have higher levels 

of selenium compounds. Some plants can build up selenium to levels that harm livestock 

feeding on them. In these areas, people could be exposed to too much selenium if they eat a lot 

of locally grown grains and vegetables or animal products that have built up high levels of 

selenium. People may also be exposed to selenium from industrial sources. Humans are 

normally not exposed to large amounts of selenium in the air, unless selenium dust or volatile 

selenium compounds are formed in their workplace. Occupations in which humans may be 

exposed to selenium in the air are the metal industries, selenium-recovery processes, paint 

manufacturing, and special trades. Chapter 6 contains more information on how people can be 

exposed to selenium. 

1.4 HOW CAN SELENIUM ENTER AND LEAVE MY BODY? 

Selenium from the environment mainly enters the body when people eat food containing 

selenium. The human body easily absorbs the organic selenium compounds (for example, 

selenoamino acids) when eaten, and makes them available where needed in the body. The 
SELENIUM 4 

1. PUBLIC HEALTH STATEMENT 

selenium in drinking water is usually in the form of inorganic sodium selenate and sodium 

selenite; these forms of selenium are also easily absorbed from the digestive tract. The human 

body can change these inorganic selenium compounds into forms that it can use. Selenium in the 

air may also enter your body when you breathe it. 

Hazardous waste sites at which selenium is present could represent a major source of exposure. 

The way that selenium can enter the body from a particular site depends on such factors as 

whether vegetables are grown in soil in which selenium from the site has been deposited, 

whether water at the site contains selenium and is able to flow into drinking water supplies, and 

whether selenium dust blows into the air. As mentioned earlier, specific conditions at a site can 

greatly influence which selenium compounds form and whether they can move in the 

environment to places where people might be exposed. Therefore, it is important to know that 

the presence of selenium at a site does not necessarily mean that people are being exposed to it. 

Specific tests of locally grown food, drinking water, and air must be done to find out whether 

exposure is occurring. You should also be aware that selenium compounds, including those used 

in some medicated dandruff shampoos, are not easily absorbed through the skin. 

Most of the selenium that enters the body quickly leaves the body, usually within 24 hours. 

Beyond what the body needs, selenium leaves mainly in the urine, but also in feces and breath. 

Selenium in the urine increases as the amount of the exposure goes up. Selenium can build up in 

the human body, however, if exposure levels are very high or if exposure occurs over a long 

time. The amount that builds up in the body depends on the chemical form of the selenium. It 

builds up mostly in the liver and kidneys but also in the blood, lungs, heart, and testes. Selenium 

can build up in the nails and in hair, depending on time and amount of exposure. Chapter 3 

contains more information on how selenium enters and leaves the human body. 

1.5 HOW CAN SELENIUM AFFECT MY HEALTH? 

To protect the public from the harmful effects of toxic chemicals and to find ways to treat people 

who have been harmed, scientists use many tests. 
SELENIUM 5 

1. PUBLIC HEALTH STATEMENT 

One way to see if a chemical will hurt people is to learn how the chemical is absorbed, used, and 

released by the body; for some chemicals, animal testing may be necessary. Animal testing may 

also be used to identify health effects such as cancer or birth defects. Without laboratory 

animals, scientists would lose a basic method to get information needed to make wise decisions 

to protect public health. Scientists have the responsibility to treat research animals with care and 

compassion. Laws today protect the welfare of research animals, and scientists must comply 

with strict animal care guidelines. 

The general public rarely breathes high levels of selenium, although some people may be 

exposed to selenium dust and selenium compounds in workplace air. Dizziness, fatigue, and 

irritation of mucous membranes have been reported in people exposed to selenium in workplace 

air at concentrations higher than legal levels. In extreme cases, collection of fluid in the lungs 

(pulmonary edema) and severe bronchitis have been reported. The exact exposure levels at 

which these effects might occur are not known, but they become more likely with increasing 

amounts of selenium and with increasing frequency of exposure. 

The normal intake of selenium by eating food is enough to meet the Recommended Daily 

Allowance (RDA) for this essential nutrient. However, as discussed in Chapters 2 and 3 of this 

profile, selenium compounds can be harmful at daily dietary levels that are higher than needed. 

The seriousness of the effects of excess selenium depends on how much selenium is eaten and 

how often. Intentional or accidental swallowing of a large amount of sodium selenate or sodium 

selenite (for example, a very large quantity of selenium supplement pills) could be lifethreatening without immediate medical treatment. Even if mildly excessive amounts of selenium 

are eaten over long periods, brittle hair and deformed nails can develop. In extreme cases, 

people may lose feeling and control in arms and legs. These health effects, called selenosis, 

were seen in several villages in China where people were exposed to foods high in selenium for 

months to years. No human populations in the United States have been reported with long-term 

selenium poisoning, including populations in the western part of the country where selenium 

levels are naturally high in the soil. Because most people in the United States eat foods produced 

in many different areas, overexposure to selenium in food is unlikely to occur. 
SELENIUM 6 

1. PUBLIC HEALTH STATEMENT 

In some regions of China where soil levels of selenium are very low, not eating enough selenium 

has resulted in health effects. Selenium is used by the body in antioxidant enzymes that protect 

against damage to tissues done by oxygen, and in an enzyme that affects growth and metabolism. 

Not eating enough selenium can cause heart problems and muscle pain. Muscle pain has also 

been noted in people fed intravenously for a long time with solutions that did not contain 

selenium. Babies born early may be more sensitive to not having enough selenium, and this may 

contribute to lung effects. In the United States, selenium in food is sufficient to meet the RDA 

and prevent harmful effects from not enough selenium. 

Upon contact with human skin, industrial selenium compounds have been reported to cause 

rashes, redness, heat, swelling, and pain. Brief, acute exposure of the eyes to selenium dioxide 

as a dust or fume in workplace air may result in burning, irritation, and tearing. However, only 

people who work in industries that process or use selenium or selenium compounds are likely to 

come into contact with levels high enough to cause eye irritation. 

Studies of laboratory animals and people show that most selenium compounds probably do not 

cause cancer. In fact, some studies of cancer in humans suggest that lower-than-normal selenium 

levels in the diet might increase the risk of cancer. Other studies suggest that dietary levels of 

selenium that are higher than normal might reduce the risk of cancer in humans. However, 

taking selenium so that your daily amount is greater than that required might just increase your 

risk of selenium poisoning. 

Based on studies done until 1987, the International Agency for Research on Cancer (IARC) 

determined that selenium and selenium compounds could not be classified as to their ability to 

cause cancer in humans. However, since then, the EPA has determined that one specific form of 

selenium, called selenium sulfide, is a probable human carcinogen. Selenium sulfide is the only 

selenium compound shown to cause cancer in animals. Rats and mice that were fed selenium 

sulfide daily at very high levels developed cancer. Selenium sulfide is not present in foods, and 

it is a very different chemical from the organic and inorganic selenium compounds found in 

foods and in the environment. Also, if introduced into the environment, selenium sulfide does 

not dissolve readily in water and would probably bind tightly to the soil, further reducing any 
SELENIUM 7 

1. PUBLIC HEALTH STATEMENT 

chance of exposure. Because selenium sulfide is not absorbed through the skin, the use of antidandruff shampoos containing selenium sulfide is generally considered safe. 

Very high amounts of selenium have caused decreased sperm counts, increased abnormal sperm, 

changes in the female reproductive cycle in rats, and changes in the menstrual cycle in monkeys. 

The relevance of the reproductive effects of selenium exposure in animals studied to potential 

reproductive effects in humans is not known. Selenium compounds have not been shown to 

cause birth defects in humans or in other mammals. 

Chapter 3 contains more information on the health effects of selenium and selenium compounds 

in humans and animals. 

1.6 HOW CAN SELENIUM AFFECT CHILDREN? 

This section discusses potential health effects from exposures during the period from conception 

to maturity at 18 years of age in humans. 

Children living near selenium waste sites or coal burning plants are likely to be exposed to 

higher environmental levels of selenium through breathing, touching soil, and eating 

contaminated soil. Children living in areas of China with high selenium in the soil had higher 

levels of selenium in the blood than adults from that area. Very few studies have looked at how 

selenium can affect the health of children. Children need small amounts of selenium for normal 

growth and development. Children will probably show the same sort of health effects from 

selenium exposure as adults, but some studies suggest that they may be less susceptible to health 

effects of selenium than adults. 

We do not know if exposure to selenium could result in birth defects in people. Selenium 

compounds have not been shown to cause birth defects in humans or in other mammals. We 

have no information to suggest that there are any differences between children and adults in 

where selenium is found in the body or in how fast it enters or leaves the body. Studies in 

laboratory animals have shown that selenium crosses the placenta and enters the fetus. Studies in 
SELENIUM 8 

1. PUBLIC HEALTH STATEMENT 

humans show that infants are supplied with selenium through breast milk, and therefore, women 

who were exposed to selenium by living near a waste site might transfer selenium to their babies. 

However, babies in areas of China with high selenium in the soil did not show any signs of 

health effects due to selenium, even though some of their parents did. 

1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO SELENIUM? 

If your doctor finds that you have been exposed to significant amounts of selenium, ask whether 

your children might also be exposed. Your doctor might need to ask your state health 

department to investigate. 

Since selenium occurs naturally in the environment, we cannot avoid exposure to it. Certain 

dietary supplements and anti-dandruff shampoos contain selenium in high levels. You should 

not exceed the recommended dosages when using these products. 

Children living near selenium waste sites or coal burning plants are likely to be exposed to 

higher environmental levels of selenium through breathing, touching soil, and eating 

contaminated soil. Some children eat a lot of dirt. You should discourage your children from 

eating dirt. Make sure they wash their hands frequently and before eating. Discourage your 

children from putting their hands in their mouths or from other hand-to-mouth activity. 

The primary route of human exposure to selenium is through eating food. People who irrigate 

their home gardens with groundwater containing high levels of selenium may grow and eat 

plants that contain high levels of selenium because this element is taken up in some plants. 

Fishermen and hunters of waterfowl who regularly eat fish and game from waterways with high 

selenium content may also consume above average levels of selenium. To reduce your family’s 

exposure to selenium, obey any wildlife advisories issued by your state. Information on fish and 

wildlife advisories in your state is available from your state public health or natural resources 

department. 
SELENIUM 9 

1. PUBLIC HEALTH STATEMENT 

1.8 IS THERE A MEDICAL TEST TO DETERMINE WHETHER I HAVE BEEN 

EXPOSED TO SELENIUM? 

Selenium can be measured in the blood, urine, and fingernails or toenails of exposed individuals. 

However, since selenium is an essential nutrient normally present in foods, low levels of 

selenium are normally found in body tissues and urine. Tests for selenium are most useful for 

people who have recently been exposed to high levels. Samples of blood, urine, or nails can be 

properly collected in a physician's office and sent to a laboratory that has the special equipment 

needed to measure selenium. Urine can be used to determine short-term exposure. Because red 

blood cells last about 120 days before they are replaced by newly made red blood cells, the 

presence of selenium in red blood cells can show whether a person was exposed to selenium 

during the 120 days before testing, but not if exposed more than 120 days before testing. Toenail 

clippings can be used to determine longer-term exposure. 

Many methods are available to measure selenium levels in human tissue and the environment. 

However, none of the methods that are routinely available can measure or detect each selenium 

compound in one test, and better tests that measure lower levels of different selenium 

compounds are needed. Also, these tests cannot determine the exact levels of selenium you may 

have been exposed to or predict whether health effects will occur, even though very high 

amounts of selenium in blood are clearly related to selenosis. Some human as well as animal 

studies suggest that when people are exposed over a long period to higher-than-normal amounts 

of selenium, their bodies adjust to the higher amounts. Chapter 3 contains more information on 

studies that have measured selenium in blood and other human tissues. 

The length of time that selenium stays in the body after exposure stops depends on the form of 

selenium to which the person was exposed. Thus, it is difficult to predict how useful a test will 

be if some time has gone by since exposure stopped. Chapter 7 contains more information on the 

methods available to measure selenium in human tissues and in the environment. 
SELENIUM 10 

1. PUBLIC HEALTH STATEMENT 

1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO 

PROTECT HUMAN HEALTH? 

The federal government develops regulations and recommendations to protect public health. 

Regulations can be enforced by law. Federal agencies that develop regulations for toxic 

substances include the Environmental Protection Agency (EPA), the Occupational Safety and 

Health Administration (OSHA), and the Food and Drug Administration (FDA). 

Recommendations provide valuable guidelines to protect public health but cannot be enforced by 

law. Federal organizations that develop recommendations for toxic substances include the 

Agency for Toxic Substances and Disease Registry (ATSDR) and the National Institute for 

Occupational Safety and Health (NIOSH). 

Regulations and recommendations can be expressed in not-to-exceed levels in air, water, soil, or 

food that are usually based on levels that affect animals; then they are adjusted to help protect 

people. Sometimes these not-to-exceed levels differ among federal organizations because of 

different exposure times (an 8-hour workday or a 24-hour day), the use of different animal 

studies, or other factors. 

Recommendations and regulations are also periodically updated as more information becomes 

available. For the most current information, check with the federal agency or organization that 

provides it. Some regulations and recommendations for selenium include the following: 

The EPA Office of Drinking Water regulates the amount of selenium allowed in drinking water. 

Public water supplies are not allowed to exceed 50 ppb total selenium. 

The FDA regulations allow a level of 50 ppb of selenium in bottled water. OSHA is responsible 

for setting regulations on selenium levels allowable in the workplace. The exposure limit for 

selenium compounds in the air for an 8-hour period is 0.2 mg selenium/m3

. Chapter 8 contains 

other regulations and guidelines for selenium. 
SELENIUM 11 

1. PUBLIC HEALTH STATEMENT 

1.10 WHERE CAN I GET MORE INFORMATION? 

If you have any more questions or concerns, please contact your community or state health or 

environmental quality department, or contact ATSDR at the address and phone number below. 

ATSDR can also tell you the location of occupational and environmental health clinics. These 

clinics specialize in recognizing, evaluating, and treating illnesses resulting from exposure to 

hazardous substances. 

Toxicological profiles are also available on-line at www.atsdr.cdc.gov and on CD-ROM. You 

may request a copy of the ATSDR ToxProfiles CD-ROM by calling the information and 

technical assistance toll-free number at 1-888-42ATSDR (1-888-422-8737), by email at 

atsdric@cdc.gov, or by writing at: 

Agency for Toxic Substances and Disease Registry 

Division of Toxicology 

1600 Clifton Road NE 

Mailstop E-29 

Atlanta, GA 30333 

Fax: 1-404-498-0093 

For-profit organizations may request a copy of final profiles from the following: 

National Technical Information Service (NTIS) 

5285 Port Royal Road 

Springfield, VA 22161 

Phone: 1-800-553-6847 or 1-703-605-6000 

Web site: http://www.ntis.gov/ 

SELENIUM 13 

2. RELEVANCE TO PUBLIC HEALTH 

2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO SELENIUM IN THE 

UNITED STATES 

Selenium is an essential micronutrient for humans and animals that is found ubiquitously in the 

environment, being released from both natural and anthropogenic sources. The principal release of 

selenium into the environment from anthropogenic sources is from coal combustion. Natural sources of 

selenium include the weathering of selenium-containing rocks and soils, and volcanic eruptions. 

Selenium is found in most rocks and soils, and naturally occurs at low concentrations in surface waters 

and groundwaters of the United States. Accumulation of selenium in agricultural drainage waters has 

been documented in basins in the western United States, particularly in California. Ambient background 

concentrations of selenium in the air are very low, generally in the nanogram per cubic meter (ng/m3

) 

range. 

Exposure of the general population to selenium is primarily by ingestion of its organic and inorganic 

forms, both of which occur naturally in the diet. The greatest portion of dietary intake occurs from 

organic forms of selenium, mainly the amino acids selenomethionine and selencysteine, in grains, cereals, 

and forage crops. The main inorganic sources of selenium in the diet are selenate and selenite, which are 

less absorbed than the organic forms. Other exposure pathways for selenium, which are of lesser 

importance, are water and air. Various estimates of the selenium intake for Americans have ranged from 

0.071 to 0.152 mg selenium/day (approximately 1–2 μg/kg/day in adults). Some people living in areas 

with high soil concentrations of selenium (as in areas of the western United States) might have higher 

exposure because of the natural selenium levels found locally, particularly if they consume crops 

primarily grown in that area. Metal industry workers, health service professionals, mechanics, and 

painters may be exposed to higher levels of selenium than the general population or workers employed in 

other trades. 

2.2 SUMMARY OF HEALTH EFFECTS 

As an essential trace element in humans and animals, selenium is a biologically active part of a number of 

important proteins, particularly enzymes involved in antioxidant defense mechanisms (e.g., glutathione 

peroxidases), thyroid hormone metabolism (e.g., deiodinase enzymes), and redox control of intracellular 
SELENIUM 14 

2. RELEVANCE TO PUBLIC HEALTH 

reactions (e.g., thioredoxin reductase). Depending upon the level of intake, selenium can have nutritional 

or possibly toxic effects. Most people in the United States are unlikely to suffer from selenium 

deficiency. Although excessive intake of selenium can cause adverse health effects, these are generally 

observed at doses more than 5 times greater than the Recommended Dietary Allowance (RDA). 

The current RDA for selenium, established by the Food and Nutrition Board of the National Research 

Council (National Academy of Sciences), is 55 μg/day for male and female adults (approximately 

0.8 μg/kg/day). This recommendation represents a decrease from the previous RDA of 70 μg/day for 

males; 55 μg/day was already the RDA for females. The current NAS Tolerable Upper Intake Level (UL) 

for selenium is 400 μg/day for adults (approximately 5.7 μg/kg/day). At the time that the RDA was in the 

process of being reevaluated (i.e., late 1990s), selenium was found to have entered the environment from 

old mining operations in some northwestern U.S. locations. This resulted in public concern about the 

potential effects of selenium on livestock grazing in the vicinity, and ultimately possible effects in 

humans consuming food products from plants and animals raised in those areas. The combination of the 

increased concern regarding selenium toxicity and the reduction in the selenium RDA indicated to 

ATSDR that an Agency reevaluation of selenium from a toxicological perspective is warranted; the 

previous version of the ATSDR Toxicological Profile for Selenium was published in 1996. 

Although selenium deficiency is not a health issue in the United States, it has been associated with two 

endemic diseases found in selenium-poor regions of China: a cardiovascular condition known as Keshan 

Disease and an osteoarthropathy called Kashin-Beck Disease. Keshan Disease is a cardiomyopathy 

characterized by cardiac enlargement, abnormal ECG patterns, cardiogenic shock, and congestive heart 

failure, with multifocal necrosis of the myocardium. The disease is reported to occur primarily in 

children and women of child-bearing age and has been successfully treated by selenium supplementation; 

however, a low incidence of cases persisting after selenium supplementation suggests that there may be 

other contributing factors. The evidence for the involvement of selenium in Kashin-Beck disease is less 

clear than for its involvement in Keshan disease. Kashin-Beck Disease is characterized by atrophy, 

degeneration, and necrosis of cartilage tissue, and occurs primarily in children between the ages of 5 and 

13 years; it also has been successfully treated with selenium supplements. Chronically ill people and 

older people have been shown to have lower organ concentrations of selenium than healthy individuals, 

but it is not clear if this is a cause or consequence of aging or illness. 

Relatively little information is available on health effects of elevated inhalation levels of selenium. The 

primary target organ in humans and laboratory animals in cases of acute, high-level inhalation exposure to 
SELENIUM 15 

2. RELEVANCE TO PUBLIC HEALTH 

selenium dusts or fumes is the lung, with cardiovascular, hepatic, nervous, and renal involvement as well. 

Lesser effects are observed in other organs/organ systems. Workers acutely exposed to high 

concentrations of elemental selenium dust have reported stomach pain and headaches, whereas workers 

briefly exposed to high levels of selenium dioxide dust experienced respiratory symptoms such as 

pulmonary edema, bronchial spasms, symptoms of asphyxiation and persistent bronchitis, elevated pulse 

rates, lowered blood pressure, vomiting, nausea, and irritability. No information is available on health 

effects in humans or laboratory animals from intermediate-duration (up to 1 year) inhalation exposure to 

selenium or selenium compounds. Regarding chronic inhalation exposure, several occupational studies 

describe respiratory effects such as irritation of the nose, respiratory tract, and lungs, bronchial spasms, 

and coughing following exposure to selenium dioxide or elemental selenium as dust. Respiratory 

symptoms similar to those reported for occupationally-exposed humans have been seen in animals 

inhaling high doses of elemental selenium fumes or dust, and studies of animals with acute inhalation 

exposure to hydrogen selenide or elemental selenium fumes or dust have reported hepatocellular 

degeneration and atrophy of the liver. 

Acute oral exposure to extremely high levels of selenium (e.g., several thousand times more than normal 

daily intake) produces nausea, vomiting, and diarrhea in both humans and laboratory animals. Acute oral 

exposure of humans to selenium has occasionally caused cardiovascular symptoms, such as tachycardia, 

but no electrocardiographic abnormalities were found in individuals from a human population chronically 

exposed to selenium. In laboratory animals, acute- and intermediate-duration oral exposure to very large 

amounts of selenium (approximately 100 times normal human intake) has produced myocardial 

degeneration in laboratory animals. 

Chronic oral intake of very high levels of selenium (10–20 times more than normal) can produce selenosis 

in humans, the major effects of which are dermal and neurological. As shown by affected populations in 

China, chronic dietary exposure to these excess levels of selenium has caused diseased nails and skin and 

hair loss, as well neurological problems, including unsteady gait and paralysis. Additional information on 

selenosis is summarized in the following subsection of this chapter. In contrast, studies of people living 

in areas of naturally occurring high selenium concentrations in the United States have not revealed 

adverse health effects in those populations. This difference may result from a lower (~2-fold) selenium 

exposure in the U.S. population compared to the Chinese population, as well as a better balanced, higher 

protein diet in the United States, which could lead to reduced toxicity of selenium through interactions 

with dietary components. 
SELENIUM 16 

2. RELEVANCE TO PUBLIC HEALTH 

Intermediate and chronic oral exposure of livestock to high levels of dietary selenium compounds also 

produces dermal and neurological effects. Studies in rats and other laboratory animals with high selenium 

tissue concentrations demonstrate that many organ systems retain selenium and are affected. The primary 

adverse effects in laboratory animals exposed to inorganic selenium salts or to selenium-containing amino 

acids are cardiovascular, gastrointestinal, hematological, hepatic, dermal, immunological, neurological, 

and reproductive, although doses causing these effects are generally at least 5 times higher than normal 

daily selenium intake. A condition (syndrome) referred to as “blind staggers” has been repeatedly 

observed in cattle feeding off vegetation in areas with high selenium content in the soil. However, the 

neurological effects have not been replicated in experimentally-exposed cattle receiving doses of 

selenium sufficient to induce hoof lesions, and thus, the neurological signs associated with “blind 

staggers” may be due to other compounds found within this vegetation. 

Some evidence for effects on the endocrine system has also been found following long-term oral exposure 

to elevated levels of dietary selenium in humans and rats. In humans, blood levels of thyroid T3 hormone 

(triiodothyronine) decreased in response to increased dietary selenium for durations of 3 months and 

longer at intakes several times higher than normal intake, although the hormone levels remained within 

the normal range. In rats, type-I-deiodinase activity decreased in response to increased exposure to 

selenium for several months, but the levels of thyroid hormones in these animals did not show a 

consistent pattern. 

Studies of Chinese populations and laboratory animals exposed to high levels of organic and/or inorganic 

selenium compounds have not found evidence of selective teratogenic effects in mammals. 

There is no evidence to support a causal association between selenium compounds and cancer in humans. 

In fact, some epidemiological and experimental evidence suggests that selenium exposure under certain 

conditions may contribute to a reduction in cancer risk. The chemopreventive potential of supplemental 

selenium is currently under research. Selenium sulfide and ethyl selenac are the only selenium 

compounds that have been shown to be carcinogenic upon oral administration in rodents; however, 

significant exposure of humans to these chemical forms of selenium is extremely unlikely. 

Additional information on main health effects of selenium in humans and animals is summarized below 

and detailed in Chapter 3. 
SELENIUM 17 

2. RELEVANCE TO PUBLIC HEALTH 

Selenosis. Following chronic oral exposure to excessive amounts of the organic selenium compounds 

in food, the two principal clinical conditions observed in humans are dermal and neurological effects, as 

described most completely in the epidemiological study of endemic selenosis in the People's Republic of 

China. The dermal manifestations of selenosis include loss of hair, deformation and loss of nails, and 

discoloration and excessive decay of teeth, while neurological effects include numbness, paralysis, and 

occasional hemiplegia. The average dietary intake of selenium associated with selenosis in these people 

has been estimated to be 1,270 μg/day (~0.02 mg/kg/day, or 10–20 times higher than normal daily 

intake). 

Loss of hair and malformation of hooves in pigs, horses, and cattle, and poliomyelomalacia in pigs have 

been reported to occur following long-term exposure to excessive amounts (more than 30 times the 

normal dietary amount of selenium) of the organic selenium compounds found in seleniferous plants. 

Histologically, swine with selenium-induced neurological signs exhibit bilateral macroscopic lesions of 

the ventral horn of the spinal cord. The selenium in the selenium-accumulating plant Astragalus 

bisulcatus appears to be a more potent neurotoxicant than D,L-selenomethionine or selenate. The form of 

selenium in A. bisulcatus is unknown, although it is apparently nonprotein. Myocardial degeneration has 

been experimentally produced in cattle, sheep, and swine (as well as in laboratory mammals) by acute and 

longer-term exposures to inorganic salts of selenium, but it is unclear whether seleniferous grains or 

forages, or other natural sources of selenium, cause the same cardiomyopathy. 

The neurological signs and histopathology observed in livestock following oral exposure to excess 

selenium compounds have not been recorded in laboratory animals. This suggests that (1) small 

laboratory mammals might not be appropriate models for selenium toxicity in humans due to 

toxicokinetic differences (e.g., laboratory animals absorb selenium compounds to a lesser extent, or 

metabolize and/or excrete selenium compounds more quickly), (2) some as yet unidentified organic form 

of selenium contributes to the neurological manifestations of chronic selenosis in humans and in 

livestock, (3) unrecognized confounding factors, such as other plant toxins, have contributed to the 

neurological syndrome associated with chronic selenosis in field studies of humans and livestock, and/or 

(4) species differences in interactions between selenium and other nutrients or xenobiotics, such as 

vitamin E and methionine, which have been found to be antagonistic to selenium toxicity 

Endocrine Effects. Selenium is a component of all three members of the deiodinase enzyme family, 

the enzymes responsible for deiodination of the thyroid hormones, and has a physiological role in the 
SELENIUM 18 

2. RELEVANCE TO PUBLIC HEALTH 

control of thyroid hormone levels. Significant decreases in serum T3 hormone levels have been observed 

in humans that were environmentally or experimentally exposed to elevated dietary levels of selenium 

(several times higher than normal). However, the T3 hormone levels observed in these studies were still 

within the normal human range, so the biological impact of this change is unclear. The effect of increased 

dietary selenium on other thyroid hormones is also uncertain. Intermediate-duration studies in rats show a 

decrease in type-I-deiodinase activity in response to elevated selenium; however, the levels of thyroid 

hormones in these animals did not show any consistent changes. 

Reduced growth rate of young animals and weight loss in older animals are two of the most common 

effects in experimental animals following long-term oral intake of excessive levels of inorganic and 

organic compounds of selenium. It is quite possible that selenium-induced reduction in growth has a 

thyroid or other endocrine component. For example, selenite treatment of young rats decreased 

somatomedin C levels, although somatomedin C was not a sensitive index of elevated selenium exposure 

in humans from a high-selenium area of South Dakota, and growth hormone secretion in response to the 

growth hormone releasing factor was also reduced in selenium-treated rats. The primary endocrine target 

of selenium leading to decreased growth has yet to be elucidated. Pancreatic toxicity has been observed 

following excess selenium exposure. Cytoplasmic flocculation was observed in lambs treated with a 

single oral dose of selenite, and pancreatic damage, which was not further described, was noted in rats 

following chronic oral treatment with selenate or selenite. Pancreatic toxicity associated with excessive 

selenium exposure is likely related to the unique ability of that organ to accumulate the element. 

Reproductive Effects. In humans, no correlation has been found between selenium levels in seminal 

fluid and sperm count or mobility. No significant increase in spontaneous abortions was reported among 

women chronically exposed to drinking water containing increased selenium, but the concentration was 

not considered to be unusually high. In animals, oral exposure to high doses of sodium selenate or 

selenite (at least 8 times greater than those normally supplied by an adequate diet) caused increased 

numbers of abnormal sperm, as well as testicular hypertrophy, degeneration, and atrophy in male rats, and 

affected the estrous cycle in female rats and mice. The animals that showed these effects were not mated, 

so it is not clear if fertility was affected. Oral treatment with L-selenomethionine similarly caused 

disturbances in the menstrual cycle (anovulation, short luteal and follicular phases) in monkeys. 

Selenium deficiency has also been reported to cause decreased sperm production and motility in rats. The 

relevance of the reproductive effects of high and low levels of selenium in laboratory animals to potential 

reproductive effects in humans is not known. 
SELENIUM 19 

2. RELEVANCE TO PUBLIC HEALTH 

Hepatic Effects. Liver effects have not been reported for humans exposed to excessive amounts of 

selenium. No significant abnormalities were found in blood levels of liver enzymes in people living in 

high selenium areas, or in liver morphology (ultrasonographic examination) of individuals suffering from 

severe symptoms of selenosis. In experimental animals and livestock, however, the liver has been shown 

to be affected following inhalation or oral exposure to different kinds of selenium compounds. 

Hepatocellular degeneration occurred in guinea pigs following short-term inhalation exposure to 

excessive levels (hundreds of times higher than normal) of elemental selenium dust (8 mg/m3

) or 

hydrogen selenide (33 mg/m3

). Cirrhosis, hepatocellular degeneration, and changes in liver enzyme 

levels in serum have been reported for rats, pigs, and mice orally exposed to selenite, selenate, or organic 

selenium. The oral doses of selenium producing the various adverse liver effects were approximately 

10 times the amount normally found in an adequate diet. Excessive dietary exposure to selenium sulfide 

(several thousands of times higher than normal selenium intake) produced frank hepatotoxicity in rats, but 

not in mice. Although the liver appears to be the primary target organ for the oral toxicity of selenium in 

experimental animals following intermediate and chronic exposure, liver cirrhosis or dysfunction has not 

been a notable component of the clinical manifestations of chronic selenosis in humans. The lack of 

evidence of liver damage in humans due to selenosis, despite all of the animal data to the contrary, 

suggests a problem with the animal models of the disease. 

Renal Effects. No reports of renal effects in humans were located. In animals, mild kidney effects 

have been observed following oral exposure to seleniumat levels several hundred times higher than 

normal human intake. These effects include hydropic degeneration in sheep following a single dose of 

5 mg Se/kg/day as sodium selenite. Rats appear to be more sensitive than mice to renal effects of 

repeated oral exposures to selenium compounds. A dose-related increase in renal papilla degeneration, 

described as mild to minimal, was observed in rats at very high levels of selenate or selenite (0.5 mg 

Se/kg/day, several hundreds of times higher than normal human intake) in the drinking water for 

13 weeks, although increased kidney weight was the only renal effect in similarly exposed mice. Mice 

that were given excessive daily doses of selenium sulfide by gavage (464 mg Se/kg/day for 13 weeks), 

however, developed interstitial nephritis. 
SELENIUM 20 

2. RELEVANCE TO PUBLIC HEALTH 

2.3 MINIMAL RISK LEVELS (MRLs) 

Inhalation MRLs 

No MRLs were derived for inhalation exposure to selenium because of insufficient quantitative data 

concerning both human and animal exposures. Data on the health effects of inhaled selenium in humans 

are available from studies of occupationally exposed workers (Clinton 1947; Glover 1970; Holness et al. 

1989; Kinnigkeit 1962; Wilson 1962). These studies suggest that the respiratory system is the most 

sensitive end point for inhaled selenium dust, but they do not provide quantitative measurements of 

exposure levels and are frequently confounded by concurrent exposures to other chemicals. Laboratory 

animal studies support the respiratory system as the main target of selenium inhalation toxicity (Dudley 

and Miller 1941; Hall et al. 1951), but the available data are for acute exposures to high concentrations of 

selenium that also produced serious health effects, including death. 

Oral MRLs 

No MRLs were derived for acute or intermediate oral exposure to selenium because of insufficient 

information regarding adverse health effect levels in humans and experimental animals. For acute 

exposure, no quantitative data are available from studies of humans. Some acute oral animal studies 

identify lowest-observed-adverse-effect levels (LOAELs) for organ weight changes, behavioral changes, 

and reduced body weight, but these occur at doses similar to those producing serious LOAELs for 

paralysis and developmental effects in other mammalian studies. 

Information on health effects of intermediate-duration (15–365 days) oral exposure to selenium in 

humans is mainly available from a 120-day experimental study of men who were exposed to a controlled 

diet of foods naturally low or naturally high in selenium (Hawkes and Turek 2001; Hawkes et al. 2001). 

Eleven subjects were fed diets providing selenium intake levels of 0.6 μg/kg/day for 21 days (baseline 

period), followed by 0.2 μg/kg/day (6 subjects) or 4 μg/kg/day (5 subjects) for the subsequent 99 days. 

This was more a nutritional study than a toxicological study, as indicated by selenium intake levels that 

bracketed the current RDA (~0.8 μg Se/kg/day) and were well below the tolerable upper limit (~5.7 μg 

Se/kg/day) recommended by the Food and Nutrition Board (NAS 2000). Comprehensive evaluations 

were performed that included serum levels of thyroid hormones (T3 and TSH) and reproductive hormones 

(testosterone, follicle-stimulating hormone, luteinizing hormone, prolactin, estradiol, and progesterone), 

sperm quality indices (number and concentration, motility, forward progression and velocity, and 

morphology), and immunological end points (including serum immunoglobulin levels, lymphocyte counts 
SELENIUM 21 

2. RELEVANCE TO PUBLIC HEALTH 

and phenotypes, natural-killer cell activity, proliferative response of lymphocytes to mitogenic 

stimulation, delayed-type hypersensitivity skin responses to recall antigens, and antibody responses to 

diptheria-tetanus and influenza vaccines). Effects were essentially limited to subclinical changes in 

thyroid hormones and sperm motility, which are not considered to be toxicologically meaningful. Serum 

T3 concentrations decreased in the high selenium group and increased in the low selenium group, but all 

values apparently remained within the normal human range. Serum TSH concentrations increased in the 

high-selenium group with no change in the low-selenium group, but values also remained in the normal 

range. Sperm motility was slightly lower than the baseline value in the high selenium group at study 

termination. The decrease in sperm motility cannot be clearly attributed to selenium because the effect 

was not consistent over the duration of exposure, and is unlikely to be adverse because it is at the low end 

of the normal range and was not accompanied by any changes in other indices of sperm movement 

(progression or forward velocity) or sperm numbers or morphology. 

Effects in intermediate-duration studies in experimental animals include reductions in liver enzyme 

activities, changes in liver and body weights, and histological changes in the liver and kidney, but the 

relevance of these effects to selenium toxicity in humans is questionable. For example, humans with 

selenosis did not display any changes in serum levels of liver enzymes or morphological damage to the 

liver, as shown by ultrasonographic examination (Yang et al. 1989a). Further, the liver and kidney effects 

in animal studies occurred at doses (≥0.2 mg/kg/day) that were considerably higher than the 4 μg/kg/day 

intake level that caused the subclinical thyroid hormone and sperm motility alterations in humans 

(Hawkes and Turek 2001; Hawkes et al. 2001). Although the human experimental study identifies a noobserved-adverse-effect level (NOAEL) of 4 μg/kg/day for sensitive endocrine and male reproductive end 

points, it is an inappropriate basis for derivation of an intermediate oral MRL. In particular, because this 

is a free-standing NOAEL, proximity to the LOAEL region is not known, and the use of the NOAEL to 

derive an MRL would yield a value that is in the range of the selenium RDA (approximately 

0.8 μg/kg/day) (NAS 2000) and below the chronic oral MRL derived below. 

•	 An MRL of 0.005 mg/kg/day (5 μg/kg/day) has been derived for chronic oral exposure (>365 days) 

to selenium. 

This MRL is based upon a study by Yang and Zhou (1994), who examined of a group of five individuals 

who were recovering from selenosis, and who were drawn from a larger population from an area of China 

where selenosis occurred (Yang et al. 1989a, 1989b). The study collected data on selenium levels in the 

diet, blood, nails, hair, urine, and milk of residents at three sites with low, medium, and high selenium, 

and compared the incidence of clinical symptoms of selenosis (morphological changes in fingernails) 
SELENIUM 22 

2. RELEVANCE TO PUBLIC HEALTH 

with dietary intake of selenium and selenium levels in blood. The average adult body weight was 55 kg 

(Yang et al., 1989b). It was found that selenium levels in blood corresponded to the dietary intake of 

selenium, and that symptoms of selenosis occurred at or above a selenium intake level of 910 μg/day 

(0.016 mg/kg/day) (Yang et al. 1989a). In 1992, Yang and Zhou (1994) reexamined five individuals from 

the high selenium site who had been suffering from symptoms of selenosis (loss of fingernails and hair), 

but were recovering (nails were regrowing). Since their earlier report, the living conditions of the 

population had improved; they had been cautioned against consuming high selenium foods, and part of 

their diet from locally produced corn had been replaced with rice or cereals. Yang and Zhou (1994) 

found that the concentration of selenium in the blood of these individuals had fallen from 1,346 μg/L 

(measured in 1986) to 968 μg/L (measured in 1992). Using a regression equation derived from the data in 

an earlier report (Yang et al. 1989b), it was calculated that the dietary intake of selenium associated with 

selenosis in these individuals was 1,270 μg/day, while an intake of 819 μg Se/day (was associated with 

recovery (Yang and Zhou 1994). 

The chronic oral MRL is based on a NOAEL of 819 μg/day (0.015 mg/kg/day) for disappearance of 

symptoms of selenosis in recovering individuals (Yang and Zhou 1994) and uses an uncertainty factor of 

3 for human variability. An uncertainty factor of 3 was considered appropriate because the individuals in 

this study were sensitive individuals drawn from a larger population and because of supporting studies, as 

discussed in Appendix A. The NOAEL used to derive the MRL is consistent with NOAELs observed for 

other human populations (Longnecker et al. 1991). The MRL is about 2.5–5 times higher than normal 

selenium intake levels of 71–152 μg/day (approximately 0.001–0.002 mg/kg/day) (DHHS 2002; FDA 

1982a; Levander 1987; Pennington et al. 1989; Schrauzer and White 1978; Schubert et al. 1987; Welsh et 

al. 1981), and approximately 6 times greater than the RDA for selenium of 55 μg/day 

(~0.0008 mg/kg/day) (NAS 2000). The MRL does not represent a threshold for toxicity, but a daily 

intake that ATSDR considers to be safe for all populations. The exact point above the MRL at which 

effects might occur in sensitive individuals is uncertain. 
SELENIUM 23 

3. HEALTH EFFECTS 

3.1 INTRODUCTION 

The primary purpose of this chapter is to provide public health officials, physicians, toxicologists, and 

other interested individuals and groups with an overall perspective on the toxicology of selenium. It 

contains descriptions and evaluations of toxicological studies and epidemiological investigations and 

provides conclusions, where possible, on the relevance of toxicity and toxicokinetic data to public health. 

A glossary and list of acronyms, abbreviations, and symbols can be found at the end of this profile. 

Selenium is a naturally occurring element that is widely distributed in rocks and soils. Although selenium 

has been reported at hazardous waste sites where it can occur in many forms, analysis of specific forms 

present at these sites has not been performed, and it is unclear how much selenium is present in some of 

the sites. Selenium has multiple oxidation states (valence states) including -2, 0, +4, and +6. The type of 

selenium found is a result of its oxidation state, which may vary according to ambient conditions, such as 

pH and microbial activity. 

Elemental selenium (selenium[0]) is rarely found naturally, but it is stable in soils. Selenates 

(selenium[+6]) and selenites (selenium[+4]) are water soluble and can be found in water. Sodium 

selenate is among the most mobile forms of selenium because of its high solubility and inability to adsorb 

to soil particles. More insoluble forms, such as elemental selenium, are less mobile; therefore, there is 

less risk for exposure. Because of greater bioavailability, water-soluble selenium compounds are 

probably more toxic than elemental selenium by any route. Selenium is found in nature complexed with 

multiple compounds, and although various forms are discussed in the profile, many others exist. Some 

plants, such as alfalfa, yeasts, white grain, and cruciferous species (e.g., mustard, cabbage, broccoli, and 

cauliflower), are efficient accumulators of selenium. Plants can contain organic selenium primarily in the 

form of the amino acids, selenomethionine and selenocysteine, along with the dimethyl selenides. 

Elemental selenium can be oxidized to form selenium dioxide. While the products of oxidation might be 

expected at the soil surface, elemental selenium would be the expected predominant form in soils or 

sediments where anaerobic conditions exist. Selenium sulfides, used in some anti-dandruff shampoos, are 

not very water soluble and, therefore, like elemental selenium, are relatively immobile in the 

environment. 
SELENIUM 24 

3. HEALTH EFFECTS 

Much of the selenium released to the environment comes from the burning of coal and other fossil fuels, 

and from other industrial processes such as the production of rubber. For more information on the 

physical and chemical properties of selenium, see Chapter 4. For more information on the potential for 

human exposure, see Chapter 6. 

In humans and animals, selenium is an essential nutrient that plays a role in protecting tissues from 

oxidative damage as a component of glutathione peroxidase. It is also found in the deiodinases, including 

type I and II iodothyronine 5'-deiodinase, which convert thyroxine to triiodothyronine and in thioredoxin 

reductase, which catalyses the NADPH-dependent reduction of the redox protein thioredoxin. The 

biologically active form of selenium in these enzymes is the modified amino acid, selenocysteine. 

Humans and animals can be exposed to increased amounts of selenium through the use of dietary 

supplements containing selenium. The nutritional role of selenium is further discussed in Section 3.4. 

Although selenium is an essential nutrient, exposure to high levels via inhalation or ingestion may cause 

adverse health effects. The mechanism by which selenium exerts toxic effects is unknown, but existing 

theories are discussed in Section 3.5. Most of the studies available on health effects involve exposure to 

selenite, selenate, and a form found in foods (selenomethionine). 

Several factors should be considered when evaluating the toxicity of selenium compounds. The purity 

and grade of the particular test substance used in the testing are important factors. For example, in studies 

of selenium sulfide compounds, the amounts of mono- and disulfides are often not specified by the study 

authors. The solubility and the particle size of selenium compounds can also influence their toxicity. 

3.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE 

To help public health professionals and others address the needs of persons living or working near 

hazardous waste sites, the information in this section is organized first by route of exposure (inhalation, 

oral, and dermal) and then by health effect (death, systemic, immunological, neurological, reproductive, 

developmental, genotoxic, and carcinogenic effects). These data are discussed in terms of three exposure 

periods: acute (14 days or less), intermediate (15–364 days), and chronic (365 days or more). 

Levels of significant exposure for each route and duration are presented in Tables 3-1, 3-2, and 3-3 and 

illustrated in Figures 3-1, 3-2, and 3-3. The points in the figures showing no-observed-adverse-effect 
SELENIUM 25 

3. HEALTH EFFECTS 

levels (NOAELs) or lowest-observed-adverse-effect levels (LOAELs) reflect the actual doses (levels of 

exposure) used in the studies. The oral doses presented in these tables and figures, as well as those 

included in the text of this chapter, are expressed on a per kg of body weight basis. LOAELs have been 

classified into "less serious" or "serious" effects. "Serious" effects are those that evoke failure in a 

biological system and can lead to morbidity or mortality (e.g., acute respiratory distress or death). "Less 

serious" effects are those that are not expected to cause significant dysfunction or death, or those whose 

significance to the organism is not entirely clear. ATSDR acknowledges that a considerable amount of 

judgment may be required in establishing whether an end point should be classified as a NOAEL, "less 

serious" LOAEL, or "serious" LOAEL, and that in some cases, there will be insufficient data to decide 

whether the effect is indicative of significant dysfunction. However, the Agency has established 

guidelines and policies that are used to classify these end points. ATSDR believes that there is sufficient 

merit in this approach to warrant an attempt at distinguishing between "less serious" and "serious" effects. 

The distinction between "less serious" effects and "serious" effects is considered to be important because 

it helps the users of the profiles to identify levels of exposure at which major health effects start to appear. 

LOAELs or NOAELs should also help in determining whether or not the effects vary with dose and/or 

duration, and place into perspective the possible significance of these effects to human health. 

The significance of the exposure levels shown in the Levels of Significant Exposure (LSE) tables 

(Tables 3-1, 3-2, and 3-3) and figures (Figures 3-1, 3-2, and 3-3) may differ depending on the user's 

perspective. Public health officials and others concerned with appropriate actions to take at hazardous 

waste sites may want information on levels of exposure associated with more subtle effects in humans or 

animals (LOAELs) or exposure levels below which no adverse effects (NOAELs) have been observed. 

Estimates of levels posing minimal risk to humans (Minimal Risk Levels or MRLs) may be of interest to 

health professionals and citizens alike. 

Estimates of exposure levels posing minimal risk to humans (Minimal Risk Levels or MRLs) have been 

made for selenium. An MRL is defined as an estimate of daily human exposure to a substance that is 

likely to be without an appreciable risk of adverse effects (noncarcinogenic) over a specified duration of 

exposure. MRLs are derived when reliable and sufficient data exist to identify the target organ(s) of 

effect or the most sensitive health effect(s) for a specific duration within a given route of exposure. 

MRLs are based on noncancerous health effects only and do not consider carcinogenic effects. MRLs can 

be derived for acute, intermediate, and chronic duration exposures for inhalation and oral routes. 

Appropriate methodology does not exist to develop MRLs for dermal exposure. 
SELENIUM 26 

3. HEALTH EFFECTS 

Although methods have been established to derive these levels (Barnes and Dourson 1988; EPA 1990b), 

uncertainties are associated with these techniques. Furthermore, ATSDR acknowledges additional 

uncertainties inherent in the application of the procedures to derive less than lifetime MRLs. As an 

example, acute inhalation MRLs may not be protective for health effects that are delayed in development 

or are acquired following repeated acute insults, such as hypersensitivity reactions, asthma, chronic 

bronchitis, or multiple chemical exposure. As these kinds of health effects data become available and 

methods to assess levels of significant human exposure improve, these MRLs will be revised. 

A User's Guide has been provided at the end of this profile (see Appendix B). This guide should aid in 

the interpretation of the tables and figures for Levels of Significant Exposure and the MRLs. 

3.2.1 Inhalation Exposure 

Table 3-1 and Figure 3-1 describe the health effects observed in experimental animals that inhaled 

elemental selenium dust or hydrogen selenide. Studies of other forms of selenium are not presented in the 

LSE tables and figures (Table 3-1 and Figure 3-1) because either the reporting of the studies was 

incomplete or no studies on other forms were located. All doses are expressed in terms of total selenium. 

3.2.1.1 Death 

No studies were located regarding death in humans after inhalation of elemental selenium or selenium 

compounds. 

In animals, the acute lethality of hydrogen selenide and elemental selenium dust when inhaled has been 

investigated. In guinea pigs exposed to hydrogen selenide for 2, 4, or 8 hours, 5/16 died within 10 days 

of exposure at 12 mg selenium/m3

, 3/16 died at 6 mg selenium/m3, and 8/16 died at 6 mg selenium/m3, 

respectively (Dudley and Miller 1941). 

No deaths were observed among rabbits or guinea pigs exposed to elemental selenium dust at levels of 

31 mg selenium/m3

 for 4 hours every other day for 8 exposure days (Hall et al. 1951). Higher levels were 

not tested. 
Table 3-1 Levels of Significant Exposure to Selenium - Inhalation 

a 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) 

Species 

(Strain) 

Key to 

figure 

ACUTE EXPOSURE 

Death 

1 

(NS) 

Gn Pig 4 hr

System 

NOAEL 

(mg/m3) 

Less Serious 

(mg/m3) 

LOAEL 

(mg/m3) 

Serious 

6 (3/16 died) 

Reference 

Chemical Form 

Dudley and Miller 1941 

hydrogen selenide 

2 

(NS) 

Gn Pig 8 hr 

1 (8/16 died) Dudley and Miller 1941 

hydrogen selenide 

3 

4 

(NS) 

Gn Pig 

Systemic 

(NS) 

Rat 

2 hr 

8 hr 

Resp 

12 

33 F 

(8/16 died) 

(pulmonary hemorrhage, 

pneumonitis) 

Dudley and Miller 1941 

hydrogen selenide 

Hall et al. 1951 

elemental 

Hepatic 33 (congestion; mild central 

atrophy) 

F 

Renal 33 F 

Endocr 33 F 

Bd Wt 33 F 

5 

(NS) 

Gn Pig 4 hr 

Resp 8 (pneumonitis) Dudley and Miller 1941 

hydrogen selenide 

Cardio 8 

Hepatic 8 (fatty metamorphosis, 

increased liver weight) 

Renal 8 

Endocr 8 
a Key to 

figure 

Species 

(Strain) 

NOAEL Less Serious

System (mg/m3) (mg/m3)

Exposure/ 

Duration/ 

Frequency 

(Specific Route) 

Table 3-1 Levels of Significant Exposure to Selenium 

LOAEL 

- Inhalation 

(mg/m3) 

Serious 

(continued) 

Reference 

Chemical Form 

6 

(NS) 

Gn Pig 8 d 

4hr/2d Resp 

Cardio 

Hepatic 

Renal 

Bd Wt 

33 M 

33 M 

33 M 

33 (mild congestion; mild to 

moderate interstitial 

pneumonitis; slight emphysema) 

M 

33 (congestion; central atrophy; 

fatty metamorphosis) 

M 

Hall et al. 1951 

elemental 

7 

8 

(NS) 

8 d 

4hr/2d 

Rabbit 

Immuno/ Lymphoret 

(NS) 

Rat 8 hr

Resp 

Cardio 

Hepatic 

Renal 

Bd Wt 

33 F 

33 F 

33 F 

33 F 

33 

33 F (congestion, mild pneumonitis) 

Hall et al. 1951 

elemental 

Hall et al. 1951 

elemental 
Table 3-1 Levels of Significant Exposure to Selenium - Inhalation (continued) 

Exposure/ LOAEL 
 

Duration/ a Reference Key to Species Frequency NOAEL Less Serious Serious 

figure (Strain) (Specific Route) System (mg/m3) (mg/m3) (mg/m3) Chemical Form 

9 Gn Pig 4 hr Dudley and Miller 1941

8 (splenic hyperplasia) (NS) hydrogen selenide 

a The number corresponds to entries in Figure 3-1. 

Bd Wt = body weight; Cardio = cardiovascular; CEL = cancer effect level; d = day(s); (F) = feed; Endocr = endocrine; F = female; gastro = gastrointestinal; Hemato = hematological; hr = 

hour(s); LOAEL = lowest-observed-adverse-effect level; M = male; Metab = metabolic; Musc/skel = musculoskeletal; NOAEL = no-observed-adverse-effect level; (NS) = not specified; 

Resp = respiratory 

SELENIUM 31 

3. HEALTH EFFECTS 

All LOAEL values from each reliable study for death in each species and duration category are recorded 

in Table 3-1 and plotted in Figure 3-1. 

3.2.1.2 Systemic Effects 

The selenium compounds that are most likely to be encountered in air in occupational settings are dusts of 

elemental selenium, hydrogen selenide, and selenium dioxide. Other volatile selenium compounds (e.g., 

dimethyl selenide, dimethyl diselenide) might be encountered in some naturally occurring situations. 

Because selenium is converted from one form to another, as in plant biosynthesis of selenoamino acids, it 

is not clear which specific forms may be encountered at hazardous waste sites. If a hazardous waste site 

specifically contains deposits of compounds of selenium, those compounds could be released off-site in 

dust or air. Toxicity data for exposures via inhalation are available for elemental selenium, selenium 

dioxide, selenium oxychloride, hydrogen selenide, and dimethyl selenide. Because there are few studies 

of inhalation of selenium of any single form, all available studies of inhalation exposures to selenium 

compounds will be included in this discussion. 

In studies of human occupational exposures, it appears that the respiratory tract is the primary site of 

injury after inhalation of selenium dust or selenium compounds, but gastrointestinal (possibly due to 

swallowed selenium) and cardiovascular effects, as well as irritation of the skin and eyes, also occur. 

Little of the available information for humans, however, relates health effects exclusively to measured 

concentrations of the selenium dust or compounds because of the possibility of concurrent exposures to 

multiple substances in the workplace. In animals, the respiratory tract is also the primary site of injury 

following inhalation exposure to selenium dust and hydrogen selenide. Hematological and hepatic effects 

have also been noted in animals. Inhalation data from laboratory animal studies are available only for 

acute exposures. 

No information was located regarding hematological, musculoskeletal, dermal, or ocular effects in 

humans or laboratory animals after inhalation exposure to selenium or selenium compounds. The 

systemic effects that have been observed after inhalation exposure are discussed below. The highest 

NOAEL values and all LOAEL values for each reliable study for systemic effects in each species and 

duration category are recorded in Table 3-1 and plotted in Figure 3-1. 
SELENIUM 32 

3. HEALTH EFFECTS 

Respiratory Effects. In humans, the respiratory system is the primary site of injury after inhalation 

of elemental selenium or selenium compounds. The largest number of reported human exposures 

occurred in occupational settings, especially in industries that extract, mine, treat, or process seleniumbearing minerals and in industries that use selenium or selenium compounds in manufacturing. The 

reports of occupational exposure do not link observed symptoms to specific air concentrations of 

elemental selenium or selenium compounds. Several reports, however, have noted common effects 

associated with inhalation exposure in occupational settings. 

Selenium dioxide is formed when selenium is heated in air. Direct exposure to selenium dioxide is, 

therefore, primarily an occupational hazard and not likely to be a risk at hazardous waste sites. Selenium 

dioxide forms selenious acid on contact with water, including perspiration, and can cause severe irritation. 

Acute inhalation of large quantities of selenium dioxide powder can produce pulmonary edema as a result 

of the local irritant effect on alveoli (Glover 1970). Bronchial spasms, symptoms of asphyxiation, and 

persistent bronchitis have been noted in workers briefly exposed to high concentrations of selenium 

dioxide (Wilson 1962). Kinnigkeit (1962) reported that selenium dioxide concentrations of 0.007– 

0.05 mg selenium/m3

 in a selenium rectifier plant produced slight tracheobronchitis in 9 of 62 exposed 

workers. 

Hydrogen selenide, a highly poisonous selenium compound, is a gas at room temperature, with a density 

much higher than air. Selenium oxychloride, also highly toxic, is more irritating and corrosive to the 

human respiratory tract than are other forms of selenium because the compound hydrolyzes to hydrogen 

chloride (HCl), which can then form hydrochloric acid in humid air and in the respiratory tract (Dudley 

1938). Hydrogen selenide and selenium oxychloride are occupational exposure hazards that are not 

expected to be much of a concern at hazardous waste sites. 

Acute inhalation exposure to elemental selenium dust, possibly including some selenium dioxide, in 

occupational settings has been shown to irritate mucous membranes in the nose and throat and produce 

coughing, nosebleed, loss of olfaction, and in heavily exposed workers, dyspnea, bronchial spasms, 

bronchitis, and chemical pneumonia (Clinton 1947; Hamilton 1949). Chronic exposure of 40 workers at a 

copper refinery produced increased nose irritation and sputum (Holness et al. 1989). The exact 

concentration of selenium was not given, but the concentration was reported to exceed 0.2 mg 

selenium/m3

. Confounding variables in this study include concurrent exposure to several other metals 

including copper, nickel, silver, lead, arsenic, and tellurium. 
SELENIUM 33 

3. HEALTH EFFECTS 

In experimental animals, the respiratory tract is the primary site of injury following acute inhalation 

exposure to elemental selenium and selenium compounds. Rats exposed to selenium fumes (selenium 

concentration and particle size were not reported) for 2–16 minutes experienced moderate to severe 

respiratory effects, including hemorrhage and edema of the lungs (Hall et al. 1951). Rats exposed to 

selenium dust (average particle diameter, 1.2 μm) at levels of 33 mg selenium/m3

 for 8 hours experienced 

severe respiratory effects, including hemorrhage and edema of the lungs, and several animals died (Hall et 

al. 1951). Histopathological examinations of surviving animals revealed chronic interstitial pneumonitis. 

Acute exposure of rabbits and guinea pigs to selenium dust (average particle diameter, 1.2 μm) at a 

concentration of 33 mg selenium/m3

 resulted in mild interstitial pneumonitis or congestion, and slight 

emphysema in both species (Hall et al. 1951). Other histological findings included vascular lymphocytic 

infiltration and intra-alveolar foci of large macrophages. 

Acute inhalation exposure of guinea pigs to 8 mg selenium/m3

 as hydrogen selenide for 4 hours produced 

diffuse bronchopneumonia and pneumonitis (Dudley and Miller 1941). The investigators do not indicate 

if any of these guinea pigs died as a result of the exposure. Histologic examination of animals that died 

following exposure to higher concentrations revealed thickening of the alveolar walls and congestion of 

alveolar capillaries (Dudley and Miller 1937). In contrast, 1-hour exposure of rats to 25,958 mg 

selenium/m3 as dimethyl selenide produced only minor effects (increased weight of lung and liver) 1 day 

postexposure. These changes disappeared by 7 days postexposure (Al-Bayati et al. 1992). Enzymatic 

methylation of selenium compounds is the primary route of detoxification and may explain the low 

toxicity of dimethyl selenide (Al-Bayati et al. 1992). Although this form of selenium is environmentally 

relevant since it is formed in soil, plants, and microorganisms, dimethyl selenide appears to be relatively 

nontoxic in comparison to occupational exposure to hydrogen selenide. 

The effects of intratracheal instillation of selenium on pulmonary function may be dependent on the form 

in which it is supplied (Nonavinakere et al. 1999). Instillation of 0.06 mg selenium/100 g body weight as 

selenium dioxide produced a significant decrease in respiratory rate and a significant increase in lung 

resistance compared with controls. Instillation with 0.06 mg selenium/110 g body weight as seleno-Lmethionine also produced a decrease in respiratory rate and an increase in lung resistance, but the values 

were not significantly different from controls. 

Intratracheal instillation of 0.3 mg selenium as sodium selenite in male Hartley-guinea pigs decreased 

dynamic-lung-compliance and increased pulmonary resistance compared with control animals instilled 

with saline (Bell et al. 1997). Analysis of bronchoalveolar-lavage fluid showed increased activities of 
SELENIUM 34 

3. HEALTH EFFECTS 

lactate dehydrogenase, β-glucuronidase, alkaline phosphatase, and protein, suggesting damage to lung 

tissue. 

Histological analysis of guinea pigs that received single intratracheal instillations of 0.3 mg selenium as 

sodium selenite found mild acute inflammation in approximately one-third of the lung tissue and a 

noticeable amount of sloughed epithelium and mucus within the bronchi (Bell et al. 2000). Lungs of 

animals treated with 0.06 mg selenium showed neutrophils aggregated in the alveoli and some dilation of 

the alveoli suggestive of emphysema. Relative lung weights and the ratio of wet/dry lung weight were 

increased in the selenium-treated animals compared with controls; the increase was only significant for 

those receiving the higher dose of selenium. Leukocyte counts in bronchoalveolar-lavage fluid were 

decreased for selenium-treated animals compared with controls, and the difference was significant for the 

animals receiving 0.3 mg selenium, but not the 0.06 mg dosage. 

No studies were located regarding respiratory effects in animals after intermediate or chronic inhalation of 

selenium or selenium compounds. 

Cardiovascular Effects. Several workers experienced symptoms of shock, including lower blood 

pressure and elevated pulse rates, following an acute exposure (at most 20 minutes) to selenium dioxide 

fumes resulting from a fire (Wilson 1962). The subjects were treated with oxygen and inhalation of 

ammonia vapor, and pulse rates were normalized within 3 hours. 

Cardiovascular effects were not observed in guinea pigs exposed to hydrogen selenide at 8 mg 

selenium/m3

 for 4 hours (Dudley and Miller 1941), or in guinea pigs and rabbits exposed to elemental 

selenium dust (average particle diameter, 1.2 μm) every other day at 33 mg selenium/m3

 for eight 4-hour 

exposure periods (Hall et al. 1951). 

Gastrointestinal Effects. Vomiting and nausea were reported in workers exposed to high 

concentrations of selenium dioxide for a maximum of 20 minutes during a fire (Wilson 1962). Stomach 

pain was frequently reported by workers exposed to elemental selenium and selenium dioxide at a 

selenium rectifier plant (Glover 1967), and by copper refinery workers exposed to an unspecified form of 

selenium (Holness et al. 1989). Exposure concentrations were not reported for the rectifier plant, but 

were >0.2 mg selenium/m3

 at the copper refinery. 
SELENIUM 35 

3. HEALTH EFFECTS 

No studies were located regarding gastrointestinal effects in animals after inhalation of selenium or 

selenium compounds. 

Hepatic Effects. No studies were located regarding hepatic effects in humans after inhalation of 

selenium or selenium compounds. 

Hepatoxicity has been observed in experimental animals following inhalation exposure to elemental 

selenium dust and to hydrogen selenide. One month after an 8-hour exposure to elemental selenium dust 

at a level of 33 mg selenium/m3

, most rats exhibited slight liver congestion and a few exhibited mild 

centrilobular atrophy (Hall et al. 1951). In contrast, 1 week after exposure to 25,958 mg selenium/m3

 as 

dimethyl selenide for 1 hour, rats showed no observable changes in the liver (Al-Bayati et al. 1992). 

Three weeks following acute exposure to elemental selenium dust at a level of 33 mg selenium/m3

 for 

4 hours every other day for 8 days, 4/10 guinea pigs exhibited slight hepatic congestion with mild central 

atrophy and 2/10 showed some fatty hepatocellular degeneration (Dudley and Miller 1941). In contrast, 

exposure of guinea pigs to lower concentrations of selenium (8 mg/m3

), as hydrogen selenide, for a single 

4-hour period produced mild fatty hepatocellular metamorphosis (Dudley and Miller 1941). 

Renal Effects. No studies were located regarding renal effects in humans after inhalation of selenium 

or selenium compounds. 

The kidneys do not appear to be affected in guinea pigs (Dudley and Miller 1941; Hall et al. 1951) after 

acute inhalation exposure to 33 mg selenium/m3

 as hydrogen selenide for 8 hours or to 8 mg selenium/m3 

as elemental selenium dust for 4 hours. Likewise, the kidneys were not affected in rabbits following 

acute inhalation exposure to 33 mg selenium/m3

 as hydrogen selenide for 8 hours (Hall et al. 1951) or in 

rats following acute inhalation exposure to 25,958 mg selenium/m3 as dimethyl selenide for 1 hour or to 

33 mg selenium/m3

 as hydrogen selenide for 8 hours (Al-Bayati et al. 1992; Hall et al. 1951). 

Endocrine Effects. No studies were located regarding endocrine effects in humans after inhalation of 

selenium or selenium compounds. 

No histopathological changes in the adrenal gland were observed in guinea pigs exposed to hydrogen 

selenide at 8 mg selenium/m3

 for 4 hours (Dudley and Miller 1941) or in rats exposed to elemental 

selenium at 33 mg selenium/m3

 for 8 hours (Hall et al. 1951). 
SELENIUM 36 

3. HEALTH EFFECTS 

Body Weight Effects. No studies were located regarding effects on body weight in humans 

following inhalation of selenium or selenium compounds. 

No effects on body weight were observed in guinea pigs following a single 8-hour exposure to elemental 

selenium at 33 mg selenium/m3

 or in guinea pigs and rabbits exposed to elemental selenium dust at 33 mg 

selenium/m3 every other day for 4 hours for a total of eight exposures (Hall et al. 1951). 

3.2.1.3 Immunological and Lymphoreticular Effects 

No studies were located regarding immunological or lymphoreticular effects in humans after inhalation 

exposure to selenium or selenium compounds. 

Lymphoid hyperplasia was noted in the spleen of guinea pigs following a single 4-hour exposure at 8 mg 

selenium/m3 as hydrogen selenide (Dudley and Miller 1941). Histopathological changes in the spleen 

were not observed in guinea pigs exposed to elemental selenium dust (average particle diameter, 1.2 μm) 

at 33 mg selenium/m3

 for 8 hours (Hall et al. 1951). Injury to the spleen was observed in guinea pigs 

following exposure for 4 hours, every other day, for 8 days to elemental selenium dust at a level of 33 mg 

selenium/m3

 (Hall et al. 1951). Specific effects included congestion of the spleen, fissuring red pulp, and 

increased polymorphonuclear leukocytes (Hall et al. 1951). 

3.2.1.4 Neurological Effects 

Information concerning possible neurological effects caused by inhalation of selenium or selenium 

compounds is limited. Severe frontal headaches were reported by workers exposed during an accident to 

high concentrations of selenium fumes (compound not stated) for approximately 2 minutes (Clinton 

1947). Workers at a selenium rectifier plant reported symptoms of malaise and irritability when working 

with selenium (exposure was probably to selenium dioxide and elemental selenium, but the form was not 

stated) (Glover 1967). The symptoms resolved whenever the workers were moved to other work. 

Urinary concentrations of selenium were about 0.08 mg/L, compared to 0.024–0.034 mg/L in unexposed 

workers. 

No studies were located regarding neurological effects in animals after inhalation of selenium or selenium 

compounds. 
SELENIUM 37 

3. HEALTH EFFECTS 

No studies were located regarding the following health effects in humans or animals after inhalation 

exposure to selenium or selenium compounds: 

3.2.1.5 Reproductive Effects 

3.2.1.6 Developmental Effects 

3.2.1.7 Cancer 

There are no epidemiologic data that support a causal association between the inhalation of elemental 

selenium dusts or selenium compounds and the induction of cancer in humans (Gerhardsson et al. 1986; 

Wester et al. 1981). In one study, postmortem samples were collected from copper smelter workers who 

were exposed to several different airborne compounds, including selenium compounds. Samples from 

lung cancer cases had lower concentrations of selenium in lung tissue than samples from controls or from 

workers who had died from other causes (Gerhardsson et al. 1986). In another autopsy study of smelter 

workers, Wester et al. (1981) found that the selenium concentrations in kidney tissues from workers who 

had died of malignancies were lower than the selenium concentrations in kidney tissues from workers 

who died of other causes. Further discussions regarding the cancer protective effects of selenium can be 

found in Section 3.2.2.7. 

No studies were located regarding carcinogenic effects in laboratory animals after inhalation exposure to 

selenium or selenium compounds. 

3.2.2 Oral Exposure 

Table 3-2 and Figure 3-2 describe the health effects observed in humans and experimental animals 

associated with dose and duration of oral exposure to selenium and selenium compounds (i.e., elemental 

selenium dust, selenium dioxide dissolved in water [selenious acid], sodium selenate, sodium selenite, 

potassium selenate, and dietary selenium compounds, which include selenoamino acids). All doses for 

these compounds are expressed in terms of total selenium. Table 3-3 and Figure 3-3 describe health 

effects observed in laboratory animals following oral exposure to selenium sulfides (SeS2 and SeS) at 

varying doses and exposure durations. All doses for selenium sulfide compounds are expressed in terms 
Table 3-2 Levels of Significant Exposure to Selenium - Oral 

a 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) Species (Strain) Key to figure 

ACUTE EXPOSURE Death 

1 

(SpragueDawley) (G) 

Rat once

System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

(mg/kg/day) 

Serious 

6700 M (LD50) 

2 

(SpragueDawley) 

Rat 

(GW) 

once 

7 M (LD50) 

3 

(SpragueDawley) 

Rat 

(W) 

14 d ad lib 0.418 F (7/12 died) 

4 

(NS) 

Rat 

(G) 

once 

4.8 F (LD50) 

5 

(Wistar) 

Rat 

(GW) 

once 

48 (LD50) 

6 

(NS) 

Mouse 

(G) 

once 

3.2 M (LD50) 

7 

(ICR) 

Mouse 

(G) 

once 

35.9 M (LD50) 

8 

(Swiss) 

Mouse 

(GW) 

once 

16 M (LD50) 

9 

(NS) 

Gn Pig 

(G) 

once 

2.3 F (LD50) 
Table 3-2 Levels of Significant Exposure to Selenium - Oral	 (continued) 

Exposure/ LOAEL
 

Duration/

a 

Key to Species Frequency NOAEL Less Serious Serious 

(Specific Route) figure (Strain)	 System (mg/kg/day) (mg/kg/day) (mg/kg/day) 

10 Rabbit	 once 

1 F (LD50) (NS) (G) 

Systemic 

11 Rat 14 d 

Bd Wt 0.251 F	 0.418 F (significant (36%) reduction in ad lib (Sprague- body weight) 

Dawley) (W)
 

12 Mouse	 14 d 

ad lib Hemato 0.38 M 0.82 M (significant increase in red blood (BALB/c) cell count)	 

(W) 

Hepatic 0.38 M 0.82 M (significant decrease in relative 

liver weight) 

Renal 0.17 M 0.38 M (significant increase in relative 

kidney weight) 

Bd Wt 0.38 M 0.82	 (significant decrease in body 

weight gain) 

13 Mouse	 14 d 

ad lib Hemato 1.36 M
 (BALB/c) 

(W) 

Hepatic 1.36 M Renal 1.36 M Bd Wt 1.36 M 
Table 3-2 Levels of Significant Exposure to Selenium - Oral (continued) 

a 

Key to 

figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

(mg/kg/day) 

Serious 

14 

(NS) 

Pig 5 d Resp 1.25 

Cardio 1.25 Hepatic 1.25 Renal 1.25 Dermal 1.25 Bd Wt 1.25 (5% loss of body weight) 

Immuno/ Lymphoret 

15 

(BALB/c) 

Mouse 

(W) 

14 d ad lib 0.38 M 0.82 (increased proliferation of 

splenic lymphocytes and LPS-induced production of TNF alpha and IL-1beta) 

M 

16 

(BALB/c) 

Mouse 

(W) 

14 d ad lib 1.36 M 

Neurological 

17 

(Swiss) 

Mouse 

(GW) 

once 

1.6 (decreased activity, muscle 

tone, touch response, respiration; hypothermia) 

18 

(BALB/c) 

Mouse 

(W) 

14 d ad lib 0.24 M 0.58 (significant increase in the 

levels of striatal dihydroxyphenylacetic acid and homovanillic acid) 

M 
Table 3-2 Levels of Significant Exposure to Selenium - Oral	 (continued) 

Exposure/ LOAEL
 

Duration/

a 

Key to Species Frequency NOAEL Less Serious Serious 

(Specific Route) figure (Strain)	 System (mg/kg/day) (mg/kg/day) (mg/kg/day) 

19 Mouse	 14 d 

ad lib 1.96 M (BALB/c) 

(W) 

20 Pig	 10 d 

1.3 (hypoactivity, focal symmetrica

1x/d (NS)	 poliomalacia, histopathological 

(C) lesions in brain and spinal cord

Developmental 

21 Hamster once 

Gd 8 7.1	 7.9 (encephalocele; decreased (Syrian LKV) crown-rump length) 

(GW)
 

22 Hamster	 once 

Gd 8 7.1 (encephalocele) (Syrian LKV) 

(GW)
 

23 Hamster once 

Gd 8 5.9 (decreased fetal crown-rump (Syrian LKV) length) 

(GW) 

INTERMEDIATE EXPOSURE Death 

24 Rat 6 wk 

0.48 M (1/8 died) ad lib (Sprague- 

Dawley) (F)
 

25 Rat	 6 wk 

0.4 M (1/8 died) ad lib (Sprague- 

Dawley) (F)
 

26 Rat	 13 wk 

2.54 (20/20 died) (Fischer- 344) (W) 
a 

Key to 

figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) 

NOAEL Less Serious

System (mg/kg/day) (mg/kg/day)

Table 3-2 Levels of Significant Exposure to Selenium -

LOAEL 

Oral 

(mg/kg/day) 

Serious 

(continued) 

27 

(Fischer- 344) (W) 

Rat 13 wk 1.67 F (2/10 died) 

28 

(SpragueDawley) 

Rat 

(W) 

4-6 wk ad lib 0.84 M (4/6 died) 

29 

(SpragueDawley) 

Rat 

(W) 

4-6 wk ad lib 0.84 M (2/6 died) 

30 

(Wistar) 

Rat 

(W) 

1 yr daily ad lib 

1.05 M (1/3 died) 1.05 F (3/5 died) 

31 

(BLU:[LE]) 

Rat 

(W) 

365 d 

0.28 

(50% males died at 58 days 50% females died at 160 days

32 33 

(ICR) 

Mouse Systemic Human 

(G) 

30 d 6d/wk 

(IN) 

20 wk 

Endocr 0.001 

14.2 M (15/15 died) 

34 Human 

(F) 

102d 

Endocr 0.0039 M 
a 

Key to 

figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) 

NOAEL Less Serious

System (mg/kg/day) (mg/kg/day)

Table 3-2 Levels of Significant Exposure to Selenium 

LOAEL 

- Oral 

(mg/kg/day) 

Serious 

(continued) 

35 Human 

(F) 

120d 

Hemato 0.004 M 

36 

(Macaca fascicularis) 

Monkey 

(GW) 

gd 20-50 1x/d Gastro 

Bd Wt 

0.025 F 0.025 F 

0.15 F (vomiting) 0.15 F (increased weight loss) 

37 

(Wistar) 

Rat 

(F) 

110 d ad lib Endocr 

Bd Wt 

0.105 M 0.105 M 

0.105 (significant reduction in type I 

deiodinase activity) 

M 

38 

(Wistar) 

Rat 

(F) 

110 d ad lib Endocr 

Bd Wt 

0.118 (significant reduction in type I 

deiodinase activity) 

M 

0.118 (significant reduction in body 

weight (15%)) 

M 

39 

(SpragueDawley) 

Rat 

(F) 

2 mo ad lib Hepatic 

Bd Wt 

0.1 M 0.2 M 

0.2 (nodular regenerative 

hyperplasia, increased relative liver weight) 

M 
Table 3-2 Levels of Significant Exposure to Selenium - Oral	 (continued) 

Exposure/ LOAEL
 

Duration/

a 

Key to Species Frequency NOAEL Less Serious Serious 

(Specific Route) figure (Strain)	 System (mg/kg/day) (mg/kg/day) (mg/kg/day) 

40 Rat 8 wk 

Resp 0.45 M (Sprague- (F)	 

Dawley) 

Cardio 0.45 M Gastro 0.45 M Hepatic 0.45 M (diffuse panlobular vacuolar 

accumulation of glycogen and lipid) 

Renal 0.45 M Bd Wt 0.25 M (final body weights about 14% 0.35 M (final body weights about 29% 

lower than controls) lower than controls) 

41 Rat	 40 d 

ad lib Hemato 0.27 M
 (Sprague- 

Dawley) (F)
 

Endocr 0.026 M 0.055 M (significant reduction in serum 

tri-iodothyronine levels) 

Bd Wt 0.27 M 

42 Rat	 6 wk 

ad lib Hemato 0.24 M 0.32 M (23% decrease in hemoglobin) 0.56 M (79% decrease in hemoglobin) (Sprague- 

Dawley) (F) 

Hepatic	 0.4 M (6-fold increase in bilirubin) 

Endocr 0.32 M 0.4 M (pancreas weight 1.4 times 

greater than diet restricted controls) 

Bd Wt 0.32 0.4 M (body weight gain 36% lower 

than controls) 
Table 3-2 Levels of Significant Exposure to Selenium - Oral (continued) 

Exposure/ LOAEL
 

Duration/

a 

Key to Species Frequency NOAEL Less Serious Serious 

(Specific Route) figure (Strain) System (mg/kg/day) (mg/kg/day) (mg/kg/day) 

43 Rat 6 wk 

ad lib Endocr 0.09 M (significant increase in serum (Sprague- TSH (~30%)) 

Dawley) (F)
 

Bd Wt 0.09 M Metab 0.09 M (significant increase in GSH-Px 

in kidney (~30%) and erythrocytes (~100%)) 

44 Rat 3 mo 

1x/d Hepatic 0.002 M (sporadic infiltrations of 0.005 M (distict swelling of Kupffer cells (Wistar) mononuclear cells in portal in dilated sinusoidal vessels an

(F) canals and weak activation of necrotic areas comprising sing

Kupffer cells) groups of hepatocytes) 
Table 3-2 Levels of Significant Exposure to Selenium - Oral	 (continued) 

Exposure/ LOAEL
 

Duration/

a 

Key to Species Frequency NOAEL Less Serious Serious 

(Specific Route) figure (Strain)	 System (mg/kg/day) (mg/kg/day) (mg/kg/day) 

45 Rat 13 wk 

Resp 1.57 M (Fischer- 344) (W)	 

Cardio 1.57 M Gastro 1.57 M Hemato 0.92 M 1.57 M (increased hematocrit and 

hemoglobin associated with decreased water intake) 

Musc/skel 1.57 M Hepatic 0.92 M 1.57 M (increased bile acids indicating 

cholestasis) 

Renal 0.31 F 0.47 F	 (minimal papilla degeneration of 

the kidneys) 

Endocr 1.57 M Ocular 1.57 M Bd Wt 0.47 F 0.88 F (body weights 10% less than 1.35 F (body weights 29% less than 

controls) controls, associated with 

decreased water intake) 
Table 3-2 Levels of Significant Exposure to Selenium - Oral	 (continued) 

Exposure/ LOAEL
 

Duration/

a 

Key to Species Frequency NOAEL Less Serious Serious 

(Specific Route) figure (Strain)	 System (mg/kg/day) (mg/kg/day) (mg/kg/day) 

46 Rat 13 wk 

Resp 1.67 F (Fischer- 344) (W)	 

Cardio 1.67 F Gastro 1.67 F Hemato 0.86 F 1.67 F	 (increased hematocrit 

associated with decreased water intake) 

Musc/skel 1.67 F Hepatic 1.67 F Renal 0.28 F 0.5 F	 (mild papilla degeneration) 

Endocr 1.67 F Ocular 1.67 F Bd Wt 0.98 M 1.59 M (body weights 34% less than 

controls; associated with decreased water intake) 

47 Rat	 23-29 d b b b 

ad lib Bd Wt 0.167 M 0.293 M (significant (11%) reduction in 0.418 (significant (20% male, 39% (Sprague- body weight) female) reduction in body 

Dawley) (W)
 0.209 F	 weight) 0.334 F 

48 Rat	 4-6 wk 

ad lib Hepatic 0.84 M (cirrhosis) (Sprague- 

Dawley) (W) 

Bd Wt 0.42 M (body weight gain 10% lower 

than controls) 
Table 3-2 Levels of Significant Exposure to Selenium - Oral	 (continued) 

Exposure/ LOAEL
 

Duration/

a 

Key to Species Frequency NOAEL Less Serious Serious 

(Specific Route) figure (Strain)	 System (mg/kg/day) (mg/kg/day) (mg/kg/day) 

49 Rat	 6 wk 

ad lib Bd Wt 0.125 M (Sprague- 

Dawley) (F)
 

50 Rat	 6 wk 

ad lib Bd Wt 0.125 M
 (Sprague- 

Dawley) (F)
 

51 Rat	 3-6 wks 

ad lib Endocr 0.64 F (decreased somatomedin C) (Wistar)	 

(W) 

Bd Wt 0.64 F	 (body weight gain 30% lower 

than controls) 

52 Rat	 12-14 wk 

Cardio	 0.324 (degeneration of heart tissue ad lib (Wistar)	 with disruption of myofibrils and 

sarcomeres)
 

Hepatic 0.324	 (degeneration of liver tissue wi

dilation of sinusoidal capillaries

Bd Wt 0.324	 (significant decrease in body 

weight (17%)) 

53 Mouse 90 d 

Hepatic 2.4 M 4.7 M (increased serum aspartate (ICR) (G) aminotransferase and alanine 

aminotransferase) 

Bd Wt 2.4 M 4.7 M (body weights 16% lower than 7.1 M (body weights 22% lower than 

controls) controls) 
Table 3-2 Levels of Significant Exposure to Selenium - Oral (continued) 

Exposure/ LOAEL
 

Duration/

a 

Key to Species Frequency NOAEL Less Serious Serious 

(Specific Route) figure (Strain) System (mg/kg/day) (mg/kg/day) (mg/kg/day) 

54 Mouse 13 wk 

Resp 3.83 F (B6C3F1) (W) 

Cardio 3.83 F Gastro 3.83 F Hemato 3.83 F Musc/skel 3.83 F Hepatic 3.83 F Renal 0.91 M 1.61 M (increased relative kidney 

weight; decreased water intake) 

Endocr 3.83 F Ocular 3.83 F Bd Wt 1.61 M 3.31 M (body weights 20% lower than 

controls; decreased water intake) 
Table 3-2 Levels of Significant Exposure to Selenium - Oral	 (continued) 

Exposure/ LOAEL
 

Duration/

a 

Key to Species Frequency NOAEL Less Serious Serious 

(Specific Route) figure (Strain)	 System (mg/kg/day) (mg/kg/day) (mg/kg/day) 

55 Mouse 13 wk 

Resp 7.17 F (B6C3F1) (W)	 

Cardio 7.17 F Gastro 7.17 F Hemato 7.17 F Musc/skel 7.17 F Hepatic 7.17 F Renal 1.07 M 1.87 M (increased kidney weight 

associated with decreased water intake) 

Endocr 7.17 F Ocular 7.17 F Bd Wt 1.87 2.95 M (body weights 13% lower than 5.45 M (body weights 24% lower than 

controls; decreased water controls; decreased water intake) intake) 

56 Mouse	 30 d 

6d/wk Hepatic 4.7 M 9.4 M (significant 2-3-fold increases in (ICR) aspartate aminotransferase and	 

(G) alanine aminotransferase) 

Renal 9.4 M Bd Wt 9.4 M (final body weight about 13% 18.9 M (final body weight about 29% 

lower than controls) lower than controls) 
Table 3-2 Levels of Significant Exposure to Selenium - Oral	 (continued) 

Exposure/ LOAEL
 

Duration/

a 

Key to Species Frequency NOAEL Less Serious Serious 

figure (Strain) (Specific Route) System (mg/kg/day) (mg/kg/day)	 (mg/kg/day) 

57 Mouse 12 wk 

ad lib Hepatic 0.2 M (vacuolization of hepatocytes) Balby 

(F) 

58 Mouse	 12 wk 

ad lib Cardio 0.2 M (cardiocytes have numerous Balby damaged mitochondria, large	 

(F) number of lipid droplets and 

numerous lysosomes) 

Bd Wt 0.2 M 

59 Rabbit	 3 mo 

Cardio	 0.137 (disruption of myofibrils, ad lib (New irregular sarcomeres, and 

Zealand) (F)
 diosrganization of bands in 

sarcomeres) 

Hemato 0.137 Bd Wt 0.137 

60 Pig	 8 wk 

ad lib Hepatic 1.1 (vacuolar degeneration, portal (mixed breed) fibrosis)	 

(F) 

Dermal	 1.1 (cracked hoof walls) 

Bd Wt 1.1	 (body weight gain 83% lower 

than controls, accompanied by decreased food intake) 
Table 3-2 Levels of Significant Exposure to Selenium - Oral	 (continued) 

Exposure/ LOAEL
 

Duration/

a 

Key to Species Frequency NOAEL Less Serious Serious 

(Specific Route) figure (Strain)	 System (mg/kg/day) (mg/kg/day) (mg/kg/day) 

61 Pig 35 d 

ad lib Dermal 0.014 0.25 (hoof cracking) (NS) 

(F) 

Bd Wt 0.25 0.47	 (body weight gain 78% lower 

than controls, accompanied by decreased food intake) 

62 Pig 8 wk	 

Hepatic 0.33 0.59	 (atrophic cirrhosis) ad lib (crossbred L	 

x Y) (F) 

Dermal 0.33 0.59	 (hoof cracking, alopecia, 

redness of skin, petechiae) 

63 Pig 31 +/- 14 d 

Cardio 1.25

(NS) 

Hepatic 1.25 Renal 1.25 Dermal 1.25	 (symmetrical hair loss, dry 

scaling skin, cracked overgrown hooves 3/5 pigs) 

Bd Wt 1.25	 (body weight gain 15% less 

than controls) 
Table 3-2 Levels of Significant Exposure to Selenium - Oral	 (continued) 

Exposure/ LOAEL
 

Duration/

a 

Key to Species Frequency NOAEL Less Serious Serious 

(Specific Route) figure (Strain)	 System (mg/kg/day) (mg/kg/day) (mg/kg/day) 

64 Pig 16 +/- 16 d 

Resp 1.25 (NS) Cardio 1.25 Hepatic 1.25 Renal 1.25 Dermal 1.25	 (symmetrical hair loss, dry 

scaling skin, cracked overgrown hooves 1/5 pigs) 

Bd Wt 1.25	 (body weight gain 22% less 

than controls) 

65 Pig	 34 d 

Cardio	 0.46 (vacuolation, pyknosis of nucle

ad lib (NS)	 

(F) 

Musc/skel 0.46	 (hyperplasia of sarcolemma 

nuclei; disintegration of myofibrils) 

66 Pig	 NS 

ad lib Dermal 0.4 F (2/10 alopecia; 1/10 hoof (Duroc) separation)	 

(F) 

Bd Wt 0.4 F 
Table 3-2 Levels of Significant Exposure to Selenium - Oral (continued) 

a 

Key to 

figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

(mg/kg/day) 

Serious 

67 

Hereford 

Cattle 120 d 

1x/d Resp 0.808 M 

(F) 

Cardio 0.808 M Gastro 0.808 M Musc/skel 0.808 M Hepatic 0.808 M Renal 0.808 M Endocr 0.808 M Dermal 0.158 M 0.288 M (mild parakeratosis of hoof) 0.808 (severe parakeratosis and 

epithelial hyperplasia of hoof) 

M 

Ocular 0.808 M 
a 

Key to 

figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) 

NOAEL Less Serious

System (mg/kg/day) (mg/kg/day)

Table 3-2 Levels of Significant Exposure to Selenium 

LOAEL 

- Oral 

(mg/kg/day) 

Serious 

(continued) 

68 

Hereford 

Cattle 

(F) 

120 d 1x/d Resp 

Cardio 

0.808 M 0.808 M 

Gastro 0.808 M Musc/skel Hepatic Renal 

0.808 M 0.808 M 0.808 M 

Endocr 0.808 M 

69 

Immuno/ Lymphoret 

(F) 

Human 120d

Dermal Ocular 

0.288 M 0.808 M 0.004 M 

0.808 M (mild parakeratosis of hoof) 

70 

(SpragueDawley) 

Rat 

(W) 

10 wk ad lib 0.7 (decreased delayed-type 

hypersensitivity; increased thymus weight) 

F 

71 

(BALB/c) 

Mouse 

(W) 

47 d ad lib 0.173 (reduced B-cell function and 

OVA-specific antibody concentration) 
Table 3-2 Levels of Significant Exposure to Selenium - Oral	 (continued) 

Exposure/ LOAEL
 

Duration/

a 

Key to Species Frequency NOAEL Less Serious Serious 

(Specific Route) figure (Strain)	 System (mg/kg/day) (mg/kg/day) (mg/kg/day) 

72 Mouse	 47 d 

ad lib 0.173 (reduced B-cell function and (BALB/c) OVA-specific antibody	 

(W) concentration) 

73 Mouse 47 d 

ad lib 0.173 (reduced OVA-specific antibody (BALB/c) concentration) 

(W) 

74 Cattle	 120 d 

1x/d 0.808 M Hereford 

(F) 

75 Cattle	 120 d 

1x/d 0.808 M Hereford 

(F) 

Neurological 

76 Human 120 d 

0.0048 M 

(F) 

77 Monkey	 30 d 

1x/d 0.08 0.12 F (hypothermia) (Macaca 

fascicularis) (GW)
 

78 Pig	 7 wk 

1.3 (tetraplegia, poliomyelomalacia

ad lib (mixed breed)	 

(F) 

79 Pig	 8 wk 

0.33	 0.59 (hind limb paresis, hind limb ad lib (crossbred L x ataxia, symmetric 

Y) (F) poliomylomalacia of the ventra

horn of the spinal cord) 
Table 3-2 Levels of Significant Exposure to Selenium - Oral	 (continued) 

Exposure/ LOAEL
 

Duration/

a 

Key to Species Frequency NOAEL Less Serious Serious 

(Specific Route) figure (Strain)	 System (mg/kg/day) (mg/kg/day) (mg/kg/day) 

80 Pig	 20-42d 

1	 2.1 (poliomylelomalacia, paralysis, ad lib (NS)	 difuse gliosis of the spinal cord

(F) 

81 Cattle	 120 d 

1x/d 0.808 M Hereford 

(F) 

82 Cattle	 120 d 

1x/d 0.808 M Hereford 

(F) 

Reproductive 

83 Human 102d 

0.0039 M 

(F)	 

84 Monkey	 30 d 

1x/d 0.06 F 0.08 F (altered menstrual cycle) (Macaca 

fascicularis) (GW)
 

85 Rat	 5 wk 

0.1 M (3.9% abnormal sperm; 0.2 M (24.6% abnormal sperm; (Wild)	 (F) decrease in live sperm) decreased live sperm, and 

sperm motility; decreased
 testicular weight)
 

86 Rat	 13 wk b 

0.29 M (15% decreased sperm counts) (Fischer- 344) (W)	 

0.31 F (more time in diestrus and less 

time in proestrus, estrus, and metestrus than controls) 
a 

Key to 

figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) 

NOAEL Less Serious

System (mg/kg/day) (mg/kg/day)

Table 3-2 Levels of Significant Exposure to Selenium 

LOAEL 

- Oral 

(mg/kg/day) 

Serious 

(continued) 

87 

(Fischer- 344) (W) 

Rat 13 wk

0.5 F 0.17 

b

(11% decrease epididymal sperm counts) 

M 

0.86 (more time in diestrus and less 

time in proestrus and estrus) 

F 

88 

(Wistar) 

Rat 12-14 wk 

ad lib 0.324 (testicular hypertrophy) 

89 

(IVCS) 

Mouse 

(W) 

48 d ad lib 0.17 F 0.34 (proportion of mice with longer 

estrus cycles increased by 11.8%) 

F 

90 

(B6C3F1) 

Mouse 

(W) 

13 wk 

5.45 

b

M 

7.17 F 

91 

(B6C3F1) 

Mouse 

(W) 

13 wk 

3.31 

b

M 

3.83 F 

92 

(New Zealand) 

Rabbit 

(GW) 

6 wks 1x/wk 0.001 (significant reduction in serum 

testosterone (49%)) 

M 

93 

(Duroc) 

Pig 

(F) 

NS ad lib 0.4 (decreased fertility, 

maternal toxicity) 
Table 3-2 Levels of Significant Exposure to Selenium - Oral	 (continued) 

Exposure/ LOAEL
 

Duration/

a 

Key to Species Frequency NOAEL Less Serious Serious 

(Specific Route) figure (Strain)	 System (mg/kg/day) (mg/kg/day) (mg/kg/day) 

Developmental 

94 Rat	 8 wks 

ad lib 0.64 (decrease weight gain of pups (Wistar) exposed during lactation)	 

(W) 

95 Mouse	 pre-Gd:30 d 

Gd 0-18 0.17 0.34 (decreased fetal body weight, (IVCS) ad lib	 delayed vertebral ossification) 

(W) 

96 Pig	 NS 

0.4 (increased number of deaths ad lib (Duroc)	 between birth and weaning; 

(F) reduced birth weight and 

reduced body weight at weaning) 

97 Cattle	 3 mo 

ad lib 0.265 

(F) 

CHRONIC EXPOSURE Death 

98 Rat 2 yr 

0.5 (reduced longevity from about ad lib (Wistar) 500 days to about 60-100 day

(F) 

Systemic 

99 Human >3 yr 

Endocr 0.01 F 

(F)	 
a 

Key to 

figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) 

NOAEL Less Serious

System (mg/kg/day) (mg/kg/day)

Table 3-2 Levels of Significant Exposure to Selenium 

LOAEL 

- Oral 

(mg/kg/day) 

Serious 

(continued) 

100 Human 

(F) 

>2 yr Hemato 

Musc/skel Hepatic Dermal 

0.0098 0.0098 0.0098 0.0098 

101 Human 

(F) 

lifetime 

Dermal 0.015 

c

0.023 (selenosis: sloughing of nails 

and brittle hair) 

102 Human 

(F) 

yr Cardio 

Hemato 

0.025 0.015 

Hepatic Dermal 

0.025 0.015 

103 

(Wistar) 

Rat 

(F) 

2 yr ad lib Musc/skel 

Hepatic Renal 

0.1 

0.025 0.025 

0.2 (soft bones) 0.1 (hyperplastic lesions) 0.1 (nephritis) 
Table 3-2 Levels of Significant Exposure to Selenium - Oral (continued) 

a 

Key to 

figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

(mg/kg/day) 

Serious 

104 

(OsborneMendel) 

Rat 

(F) 

24 mo ad lib Resp 0.5 F 

Gastro 0.5 F Musc/skel 0.5 F Hepatic 0.25 F (slight to moderate cirrhosis) 

Endocr 0.5 F Dermal 0.5 F 

105 

(Swiss) 

Mouse 

(W) 

lifetime ad lib Resp 0.57 (amyloidosis) 

Cardio 0.57 (amyloidosis) Hepatic 0.57 (amyloidosis) Renal 0.57 (amyloidosis) Endocr 0.57 (amyloidosis of adrenal gland) Dermal 0.57 (poor coat) 

Bd Wt 0.57 
Table 3-2 Levels of Significant Exposure to Selenium - Oral (continued) 

Exposure/ LOAEL
 

Duration/

a 

Key to Species Frequency NOAEL Less Serious Serious 

(Specific Route) figure (Strain) System (mg/kg/day) (mg/kg/day) (mg/kg/day) 

106 Mouse lifetime 

Resp 0.57 (amyloidosis) ad lib (Swiss) 

(W) 

Cardio 0.57 (amyloidosis) 

Hepatic 0.57 (amyloidosis) Renal 0.57 (amyloidosis) Endocr 0.57 (amyloidosis of adrenal gland) Dermal 0.57 (poor coat) Bd Wt 0.57 

Neurological 

107 Human yr 

0.027 0.058 (tendon hyperflexia, peripheral (F) anesthesia, pain in extremities

polyneuritis) 

Reproductive 

108 Rat 1 yr 

daily 0.21 0.35 (50% reduction in number of 1.05 (decreased fertility, pup surviva

(Wistar) ad lib pups reared in second maternal toxicity; second 

generation) generation failed to reproduce) (W) 

109 Mouse 3 gen 

0.57 (failure to breed in the third ad lib (CD) generation) 

(W) 
Table 3-2 Levels of Significant Exposure to Selenium - Oral (continued) 

a 

Key to 

figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

(mg/kg/day) 

Serious 

Developmental 

110 

(CD) 

(W) 

3 gen ad lib 

Mouse 0.57 (increased number of runts; 

postnatal lethality) 

a The number corresponds to entries in Figure 3-2. b Differences in levels of health effects and cancer effects between males and females are not indicated in Figure 3-2. Where such differences exist, only the most sensitive gender are presented. c Used to derive a chronic oral minimal risk level (MRL) of 0.005 mg/kg-day; The NOAEL is divided by an uncertainty factor of 3 (for human variability). ad lib = ab libitum; Bd Wt = body weight; Cardio = cardiovascular; CEL = cancer effect level; d = day(s); Endocr = endocrine; (F) = feed; F = female; (G) = gagastrointestinal; gd = gestation day; GHS-Px = selenium-dependent glutathione peroxidase; (GW) = gavage in water; Hemato = hematological; (IN) = ingestio50% kill; LOAEL = lowest-observed-adverse-effect level; LPS = lipopolysaccharide; M = male; metab = metabolic; mg/kg/day = milligram per kilogram per dayMusc/skel = musculoskeletal; NOAEL = no-observed-adverse-effect level; (NS) = not specified; Resp = respiratory; TNF = tumor necrosis factor; TSH = thyroid(W) = water; wk = week(s); x=time(s); yr = year(s) 







Table 3-3 Levels of Significant Exposure to Selenium Sulfides - Oral 

Exposure/ LOAEL
 

Duration/

a 

Key to Species Frequency NOAEL Less Serious Serious 

(Specific Route) figure (Strain) System (mg/kg/day) (mg/kg/day) (mg/kg/day) 

ACUTE EXPOSURE Death 

1 Rat once 

138 M (LD50) (Sprague- (G) 

Dawley)
 

2 Rat once 

75 M (3/6 died) (Wistar) (GO) 

3 Rat once 

50 (3/15 died) (Wistar) (GO) 

4 Mouse once 

3700 (LD50) (NMRI) (G) 

Systemic 

5 Rat once 

Hepatic 75 M (widespread hepatic necrosis) (Wistar) (GO) 

INTERMEDIATE EXPOSURE Death 

6 Rat 17 d 

112 M (LD50) 1x/d (Fischer- 344) b 

(G) 56 F (LD50) 

7 Mouse 17 d 

805 M (LD50) 1x/d (B6C3F1) b 

(G) 316 F (LD50) 
a 

Key to 

figure 

Species 

(Strain) 

LOAEL 

NOAEL Less Serious

System (mg/kg/day) (mg/kg/day)

Exposure/ 

Duration/ 

Frequency 

(Specific Route) 

Table 3-3 Levels of Significant Exposure to Selenium Sulfides - Oral 

(mg/kg/day) 

Serious 

(continued) 

8 

Systemic 

(Fischer- 344) 

(G) 

13 wk 7d/wk 1x/d 

Rat 

Resp Cardio 

31.6 31.6 

Gastro 31.6 Musc/skel 31.6 Hepatic 17.6 31.6 (focal necrosis) 

Renal 31.6 Endocr 31.6 Dermal 31.6 Bd Wt 31.6 
Table 3-3 Levels of Significant Exposure to Selenium Sulfides - Oral	 (continued) 

Exposure/ LOAEL
 

Duration/

a 

Key to Species Frequency NOAEL Less Serious Serious 

(Specific Route) figure (Strain)	 System (mg/kg/day) (mg/kg/day) (mg/kg/day) 

9 Mouse 13 wk 

7d/wk Resp 464 (B6C3F1)	 

1x/d 

(G)
 

Cardio 464
 Gastro 464
 Musc/skel 464
 Hepatic 464
 Renal 216 464 (interstitial nephritis)
 Endocr 464
 Dermal 464
 Bd Wt	 216 F 464 F (body weight 17% lower than 

controls) 

CHRONIC EXPOSURE Cancer 

10 Rat 103 wk 

15 (hepatocellular carcinomas 7d/wk (Fischer- 344)	 14/49 males, 21/50 females) 

1x/d 

(G) 
Table 3-3 Levels of Significant Exposure to Selenium Sulfides - Oral (continued) 

Exposure/ LOAEL
 

Duration/

a 

Key to Species Frequency NOAEL Less Serious Serious 

(Specific Route) figure (Strain) System (mg/kg/day) (mg/kg/day) (mg/kg/day) 

11 Mouse 103 wk 

100 F (hepatocellular 7d/wk (B6C3F1) carcinomas/adenomas 25/49, 

1x/d 

alveolar/bronchiolar

(G) carcinoma/adenomas 12/49) 

a The number corresponds to entries in Figure 3-3. b Differences in levels of health effects and cancer effects between males and females are not indicated in Figure 3-3. Where such differences exist, only the most sensitive gender are presented. ad lib = ab libitum; Bd Wt = body weight; Cardio = cardiovascular; CEL = cancer effect level; d = day(s); Endocr - endocrine; F = female; gastro = gastrointest= gestation day; Hemato = hematological; LOAEL = lowest-observed-adverse-effect level; M = male; Metab = metabolic; Musc/skel = musculoskeletal; NOAEno-observed-adverse-effect level; Resp = respiratory; (W) = water; wk = week(s); x = time(s); yr = year(s) 



SELENIUM 78 

3. HEALTH EFFECTS 

of the compound, because selenium sulfide preparations often exist as a variable mixture of the monoand disulfide forms, precluding accurate expression of the dose in terms of total selenium. 

Most of the available toxicity information for oral exposures to selenium compounds comes from 

domestic or experimental animal exposures to selenite, selenate, selenium sulfides (mixed), and organic 

selenium compounds (selenocystine, selenomethionine). Some of the earliest recognized effects of 

selenium were observed in livestock (cattle, sheep, and horses) that grazed on plants in areas of South 

Dakota, where soil selenium concentrations are naturally high. Selenium-associated effects observed in 

livestock include “blind staggers” and alkali disease. “Blind staggers” is an acute syndrome in which 

there is usually a slight impairment of vision, which can result in the animal straying from the herd. As 

the disease progresses, the blindness becomes more pronounced, and the animal may wander in circles. 

In the last stage, there are various degrees of paralysis and evidence of abdominal pain; death results from 

respiratory failure. However, because the effects have not been replicated in experimentally exposed 

cattle receiving doses of selenium sufficient to induce hoof lesions, the neurological signs associated with 

“blind staggers” may be due to compounds other than selenium in the vegetation. Alkali disease is a 

chronic disease in which the animals become emaciated, stiff, and lame; lose long hair from the mane and 

the tail; and the hooves become deformed. Alkali disease is also associated with atrophy of the heart and 

liver, while congestion and focal necrosis of the liver are more prominent in “blind staggers”. 

Some epidemiological studies report data from populations exposed to selenium in the food chain in areas 

with high selenium levels in soil. It is likely that selenite, selenate, and the selenium found in food and in 

dietary supplements comprise the majority of selenium compounds to which oral, off-site selenium 

exposures will occur at or near hazardous waste sites. Aside from the variation in effective dose, the 

health effects from exposure to selenate, selenite, and dietary selenium are not expected to differ greatly. 

However, oral exposures to many other compounds of selenium could occur (primarily through soil or 

edible plant ingestion) if those compounds were deposited at the site, or if local environmental conditions 

greatly favor transformation to those forms. Heavy metal selenides, aluminum selenide, tungsten 

diselenides, and cadmium selenide are used in industry and may end up in waste sites. Mobilization of 

selenium, typically as selenate in water run-off, has the potential to impact nearby plants and animals, 

thus potentially exposing people through eating game meat, local plants, and agricultural or livestock food 

products from the area. 
SELENIUM 79 

3. HEALTH EFFECTS 

3.2.2.1 Death 

Accidental selenium poisonings in humans have occurred, but few fatalities have been reported. The 

selenium doses associated with the reported deaths are unknown (Carter 1966; Koppel et al. 1986). One 

3-year-old boy died 1.5 hours after ingestion of an unknown quantity of selenious acid contained in a gunbluing preparation (Carter 1966). Clinical signs included excessive salivation, garlic odor on the breath, 

and shallow breathing. A 15-year-old female survived ingestion of a solution of sodium selenate 

estimated to have provided 22 mg selenium/kg body weight, probably because she was forced to vomit 

soon after exposure (Civil and McDonald 1978). Clinical signs included garlic odor of the breath and 

diarrhea. 

No cases of human death in the United States have been attributed to intermediate or chronic oral 

exposures to selenium or selenium compounds. In the Hubei Province of China, in an area of endemic 

selenosis, a woman who died was suffering from hemiplegia thought to have been caused by chronic 

selenosis induced by eating locally grown foods that contained high levels of organic selenium 

compounds (Yang et al. 1983). However, an autopsy was not performed and no clinical history of 

previous illness was available. 

In nonhuman animals, the most acutely toxic selenium compounds by ingestion appear to be sodium 

selenite and sodium selenate (Olson 1986). Oral LD50 values for sodium selenite, expressed as mg 

selenium/kg body weight, were reported as 4.8–7.0 in rats, 1.0 in rabbits, 3.2 in mice, and 2.3 in guinea 

pigs (Cummins and Kimura 1971; Pletnikova 1970). Minimum lethal doses of sodium selenite, expressed 

as mg selenium/kg body weight, reported for larger animals were 13–18 for pigs and 9.9–11.0 for cows 

(Miller and Williams 1940); however, these values were estimated on the basis of a small number of 

animals. Two of four 12-week-old lambs died within 16 hours of administration of 5 mg selenium/kg as 

sodium selenite (Smyth et al. 1990). Selenium dioxide is reported to have LD50 values of 16 mg 

selenium/kg for mice and 48 mg selenium/kg body weight for rats, but these values are also based on a 

small number of animals (Singh and Junnarkar 1991). An oral LD50 of 35.9 mg selenium/kg has been 

reported for L-selenocystine given to mice (Sayato et al. 1993). Elemental selenium is less toxic than 

most selenium compounds, because of its extremely low solubility; an LD50 of 6,700 mg selenium/kg 

body weight has been reported for oral administration of elemental selenium as a suspension (particle size 

1–30 μm) in 0.5% methylcellulose to rats (Cummins and Kumura 1971). 
SELENIUM 80 

3. HEALTH EFFECTS 

Lower doses of selenium can cause signs of toxicity if administered over extended periods of time. Eight 

weaned 5-week-old pigs receiving 1.3 mg selenium/kg/day as sodium selenite in gelatin capsules daily for 

10 days died during one study; only one dose level was tested (Wilson et al. 1989). Two long-tailed 

macaques administered 0.60 mg selenium/kg/day as selenomethionine by nasogastric intubation died of 

either anorexia or aspirated vomitus secondary to emesis and gastritis after 10 or 15 days of treatment 

(Cukerski et al. 1989). Seven of 12 female rats receiving diets containing 0.418 mg selenium/kg/day as 

sodium selenate for 14 days died before the end of the experiment (NTP 1996). Exposure to selenium in 

drinking water at a level of 0.84 mg selenium/kg/day as selenite or selenate for 4–6 weeks resulted in the 

death of four of six or two of six male rats, respectively (Palmer and Olson 1974). Feeding male rats diets 

containing 0.48 mg selenium/kg/day as sodium selenite or 0.4 mg selenium/kg/day as seleniferous wheat 

for 6 weeks resulted in the death of one of eight rats in each group (Halverson et al. 1966). 

Administration of sodium selenite in drinking water at a level of 0.28 mg selenium/kg/day for 58 days 

resulted in the death of 25 of 50 male rats (Schroeder and Mitchener 1971a). Mortality was observed in 

rats, but not in mice, receiving either 1.67 mg selenium/kg/day as sodium selenite or 2.54 mg 

selenium/kg/day as sodium selenate in drinking water for 13 weeks (NTP 1994). Gavage treatment of 

male mice with selenocystine 6 days per week for 30 days at a dose of 14.2 mg selenium/kg killed all 

15 treated animals, while no deaths were noted at 9.4 mg selenium/kg (Sayato et al. 1993). The longevity 

of hamsters was not affected by dietary administration of sodium selenite at a dose of 0.42 mg 

selenium/kg/day for 124–144 weeks (Birt et al. 1986). 

Sodium selenate and sodium selenite exhibit similar toxicity in female rats, but male rats appear more 

susceptible to the toxicity of sodium selenite than selenate (Palmer and Olson 1974; Schroeder and 

Mitchener 1971a). Sodium selenate in drinking water at 0.28 selenium mg/kg/day for 1 year did not 

increase mortality of male or female rats compared with control rats (Schroeder and Mitchener 1971a). 

Ingestion of 0.28 mg selenium/kg/day of sodium selenite in drinking water for 1 year did not increase 

mortality in female rats, whereas 50% of the males died by day 58 of administration (Schroeder and 

Mitchener 1971a). 

The relative acute toxicities of sodium selenite, potassium selenite, sodium selenate, and potassium 

selenate in aqueous solution have been examined in mice (Pletnikova 1970). No significant differences 

among the toxicities of the potassium and sodium salts of selenium were apparent in this study. In 

another study, rats tolerated a dose of 1.05 mg selenium/kg/day administered in drinking water as 

potassium selenate for over 8 months with no deaths, but three of five females and one of three males died 

by the end of 1 year (Rosenfeld and Beath 1954). Decreased survival was reported in rats fed sodium 
SELENIUM 81 

3. HEALTH EFFECTS 

selenate or selenite at 0.5 mg selenium/kg/day in a 2-year cancer study (Harr et al. 1967; Tinsley et al. 

1967). No mortality was observed in hamsters fed 0.42 mg selenium/kg/day as sodium selenite in the diet 

for 82–142 weeks (Birt et al. 1986). 

Selenium sulfide (i.e., selenium monosulfide) and selenium disulfide are less water soluble and are of 

lower acute toxicity than sodium selenate or sodium selenite. There are no reported human deaths due to 

ingestion of selenium sulfide. The LD50 value for the gavage administration of 1–20% selenium disulfide 

in aqueous 0.5% methylcellulose to rats was 138 mg selenium disulfide/kg (Cummins and Kimura 1971). 

When 1% selenium disulfide shampoo was administered by gavage, the LD50 value was lower (78 mg 

selenium disulfide/kg) (Cummins and Kimura 1971). The compound administered may have been a 

mixture of selenium sulfide and selenium disulfide; analysis of the compound was not reported. 

Henschler and Kirschner (1969) reported an LD50 of 3,700 mg selenium sulfide/kg for mice administered 

by gavage in aqueous 0.5% carboxymethylcellulose. Administration of single gavage doses of selenium 

monosulfide to rats produced death in 3/15 animals dosed with 50 mg/kg, 3/6 animals dosed with 

75 mg/kg, 1/2 animals dosed with 100 mg/kg, and 2/2 animals dosed with 125 mg/kg (Moore et al. 

1996b). 

In the case of selenium sulfide, mice are more tolerant than rats, and males of both species appear to be 

more tolerant than females (NTP 1980c). The daily doses producing 50% mortality for a 17-day gavage 

administration of a mixture of selenium mono- and disulfides were 112 mg selenium sulfides/kg for male 

rats, 56 mg selenium sulfides/kg for female rats, and 805 mg selenium sulfides/kg for male mice (NTP 

1980c). A 13-week gavage study using the same mixture of selenium mono- and disulfides reported 

survival as 10/10, 10/10, 10/10, 9/9, 8/9, and 6/10 in female mice and 10/10, 10/10, 10/10, 10/10, 10/10, 

and 9/10 in male mice receiving 0, 21.6, 46.4, 100, 216, and 464 mg selenium sulfides/kg/day, 

respectively (NTP 1980c). Although the researchers intended to administer selenium monosulfide to the 

animals, elemental analysis, melting point, and x-ray diffraction revealed that the compound administered 

included some selenium disulfide. No other chemical or physical analyses of the selenium compound 

administered were reported. 

The LD50 and lethal LOAEL values from each reliable study following oral exposure to elemental 

selenium dust, selenium dioxide dissolved in water (selenious acid), sodium selenate, sodium selenite, 

potassium selenate, and dietary selenium for each species and exposure duration are recorded in Table 3-2 

and plotted in Figure 3-2. The LOAEL values for death in rats and mice following acute and intermediate 
SELENIUM 82 

3. HEALTH EFFECTS 

oral exposures to selenium sulfide or selenium disulfide are recorded in Table 3-3 and plotted in 

Figure 3-3. 

3.2.2.2 Systemic Effects 

The highest NOAEL value and all LOAEL values for each reliable study for systemic effects in each 

species and duration category are recorded in Tables 3-2 and 3-3 and plotted in Figures 3-2 and 3-3. 

Respiratory Effects. Pulmonary edema and lesions of the lung have been noted in case reports of 

humans (Carter 1966; Koppel et al. 1986) and animals (Glenn et al. 1964a; Rosenfeld and Beath 1947) 

after ingestion of lethal doses of selenium compounds. Rabbits orally administered sodium selenite 

(subroute not specified) at levels approximating the LD50 (1–5 mg selenium/kg body weight) developed 

pulmonary congestion, hemorrhages, and edema; dyspnea; general muscular weakness; and asphyxial 

convulsions (Smith and Westfall 1937). Pulmonary edema and hemorrhages were observed in four sheep 

treated orally (subroute not specified) with a single dose of sodium selenite of 5 mg selenium/kg (Smyth 

et al. 1990). The lungs may be a target of acute exposure to excess selenium because the metabolite, 

dimethyl selenide, is exhaled. 

The effects of intermediate or chronic exposures to selenium compounds are less clear. Although Harr et 

al. (1967) stated that absolute lung weights decreased with increasing doses of selenite or selenate 

chronically administered to rats in the diet in a 2-year cancer study, they did not report lung weights at 

specific dose levels. Selenium administration also might have contributed to pneumonic lesions, but 

again, the authors did not statistically analyze their results or relate the severity of the effect to the doses 

of selenium administered. Respiratory effects were not observed in rats treated with selenite in the diet 

for 8 weeks at a dose of 0.45 mg selenium/kg/day (Chen et al. 1993). Effects on the lungs were not 

observed in pigs fed 1.25 mg selenium/kg as organic selenium found in the plant Astragalus bisulcatus 

for up to 5 days, or D,L-selenomethionine or selenate in the diet for up to 6 weeks (Panter et al. 1996). 

Treatment of steers with selenomethionine or selenite in food at doses up to 0.808 mg selenium/kg/day 

for 120 days did not produce any signs of respiratory distress or changes in lung weight or histology 

(O’Toole and Raisbeck 1995). Ingestion of selenium in drinking water for 13 weeks at doses up to 

1.67 and 7.17 mg selenium/kg as selenate in rats and mice, respectively, and 1.57 and 3.83 mg 

selenium/kg as selenite in rats and mice, respectively, did not cause any respiratory effects (NTP 1994). 

Nelson et al. (1943) reported that no effects on the lungs were apparent in rats administered 0.50 mg 

selenium/kg/day as seleniferous corn for 2 years. 
SELENIUM 83 

3. HEALTH EFFECTS 

An increased incidence of amyloidosis of the major organs, including the lungs, was observed in mice 

following lifetime exposure to sodium selenate or sodium selenite in drinking water at a level of 0.57 mg 

selenium/kg/day (Schroeder and Mitchener 1972). This effect was noted in 30% of control mice and 58% 

(p<0.001) of selenium-treated mice. Data for individual organs were not provided. 

Administration of lethal doses of selenium sulfide particles in carboxymethylcellulose by gavage has been 

reported to cause irregular breathing in mice (Henschler and Kerschner 1969), but not in rats (Cummins 

and Kimura 1971). No respiratory effects were seen in mice administered 464 mg selenium 

sulfides/kg/day or in rats administered 31.6 mg selenium sulfides/kg/day by gavage once daily for 

13 weeks (NTP 1980c). 

Cardiovascular Effects. Tachycardia has occasionally been reported as a result of a lethal, acute 

oral exposure to selenium compounds in humans (Carter 1966); however, the dose was not reported in 

this lethal exposure to a gun-bluing solution containing selenious acid. Although myocardial disorders 

(cardiogenic shock, congestive heart failure, arrhythmia, multifocal necrosis of the myocardium) have 

been associated with selenium deficiencies (Yang et al. 1988), none has been reported to be associated 

with chronic dietary selenosis in humans observed at doses of ≥0.016 mg/kg/day (Yang et al. 1989a). A 

preliminary study completed in China suggests that selenium supplementation (100 μg/day, form not 

stated) during pregnancy may reduce the incidence of pregnancy-induced hypertension (Li and Shi-mei 

1994). 

In contrast, postmortem studies of sheep that died from acute oral exposure to sodium selenite or sodium 

selenate have revealed petechial hemorrhages of the endocardium (Glenn et al. 1964a; Smyth et al. 1990). 

The sheep were treated with a time-weighted average dose of 0.65 or 0.9 mg selenium/kg/day as selenate 

over a 171-day period (Glenn et al. 1964a, 1964b), or a single dose of selenite at 5 mg selenium/kg 

(Smyth et al. 1990). Vacuolation and pyknosis of nuclei were observed in the hearts of pigs fed an 

unspecified form of selenium at a dose of 0.46 mg selenium/kg/day for 34 days (Stowe et al. 1992). In a 

2-year cancer study, Harr et al. (1967) reported the occurrence of myocardial hyperemia, hemorrhage, and 

degeneration, as well as pericardial edema, in young rats administered sodium selenite or sodium selenate 

in the feed at doses of 0.5 mg selenium/kg/day, although the authors did not specify the duration of 

exposure required to produce the effects. 
SELENIUM 84 

3. HEALTH EFFECTS 

Exposure of pigs to feed containing 54 mg/kg selenium for 1–7 days resulted in severe toxicity and death 

of several of the animals (Penrith and Robinson 1996). Histological examination of heart tissue from pigs 

that died revealed myocardial lesions consisting of widespread hypertrophy, atrophy, and disorganization 

of fibers, occasional fibrosis, and marked medial hypertrophy of the arterioles. 

Wistar rats administered 0.324 mg selenium/kg/day as sodium selenite in food for 12–14 weeks showed 

severe diffuse degenerative changes, including edema in the sub-endocardial connective tissue and the 

interfibers of prevascular regions, and myofibril swelling with profuse intercellular edema (Turan et al. 

1999a). Myocyte borders were irregular, and there was a loss of striations and a degeneration of the 

sarcolemma and myofibril structure and order. Examination of the mechanical function of the heart in 

vitro using either Langendorff perfusion or papillary muscle recordings showed increased coronary 

perfusion pressure, increased resting force, and increased heart rate with irregular beating. No difference 

in contractile force was observed. Chronic heart failure did not occur in any of the animals in the study. 

Cardiac damage was also observed in mice exposed to 0.2 mg selenium/kg/day as sodium selenite in food 

for 12 weeks (Skowerski et al. 1997b). Ultrastructural examination revealed cardiomyocytes that had 

numerous damaged mitochondria, a large number of lipid droplets, and numerous lysosomes. 

Hearts of New Zealand white rabbits administered 0.137 mg selenium/kg/day as sodium selenite in food 

for 3 months showed distinct, degenerative changes indicating disintegration of the internal structure of 

the myocytes (Turan et al. 1999b). Muscle fibers were fragmented and separated. Disruption and loss of 

myofibrils was observed, sarcomeres were irregular, and the I, Z, and H bands were disorganized and 

discontinuous. Mitochondria were fewer and more variable in size and shape, with disoriented cristae and 

a loss of matrix substance. Hearts of control animals (0.007 mg selenium/kg/day) had normal histology. 

Treatment of steers with selenomethionine or selenite in food at doses up to 0.808 mg selenium/kg/day 

for 120 days did not produce any changes in heart weight or histology (O’Toole and Raisbeck 1995). 

Histopathological changes in the heart were not observed in pigs fed selenium at 1.25 mg selenium/kg as 

organic selenium found in the plant A. bisulcatus for up to 5 days, or D,L-selenomethionine or selenate 

for up to 6 weeks (Panter et al. 1996). Histopathological changes were not observed in the hearts of rats 

treated with selenite in the diet for 8 weeks at a dose of 0.45 mg selenium/kg/day (Chen et al. 1993). 

Selenium administered to rats and mice in drinking water for 13 weeks at doses up to 1.57 and 7.17 mg 

selenium/kg/day as selenate, respectively, and up to 1.67 and 3.83 mg selenium/kg/day as selenite, 

respectively, did not cause any histopathological changes in the heart tissue (NTP 1994). No 
SELENIUM 85 

3. HEALTH EFFECTS 

histopathological changes were noted in mice administered 464 mg selenium sulfides/kg/day or in rats 

administered 31.6 mg selenium sulfides/kg/day by gavage once daily for 13 weeks (NTP 1980c). 

An increased incidence of amyloidosis of the major organs, including the heart, was observed in mice 

following lifetime exposure to sodium selenate or sodium selenite in drinking water at a level of 0.57 mg 

selenium/kg/day (Schroeder and Mitchener 1972). This effect was noted in 30% of control mice and 58% 

(p<0.001) of selenium-treated mice. Data for individual organs were not provided. 

Although myocardial degeneration and necrosis have been experimentally induced in laboratory animals 

and livestock including cattle, sheep, and swine by acute and longer-term exposures to inorganic salts of 

selenium, it is unclear whether seleniferous grains or forages, or other natural sources of selenium, can 

also cause cardiomyopathy (Raisbeck 2000). 

Gastrointestinal Effects. In humans, gastrointestinal distress, including nausea, vomiting, diarrhea, 

and abdominal pain, has been reported following ingestion of aqueous sodium selenate (Civil and 

McDonald 1978; Gasmi et al. 1997; Helzlsouer et al. 1985; Koppel et al. 1986; Sioris et al. 1980). Two 

studies provided an estimate of dose. In a case report by Civil and McDonald (1978), diarrhea was 

observed in a 15-year-old girl about 45 minutes after she swallowed sheep drench containing selenate at a 

dose of about 22 mg selenium/kg. This effect was observed despite the induction of vomiting shortly 

after the exposure. In a second case report of a suicide attempt, a 56-year-old man reported that vomiting, 

diarrhea, and abdominal pain occurred 1 hour after he ingested approximately 11 mg/kg selenium as 

sodium selenite (Gasmi et al. 1997). Postmortem examinations following two deaths from selenium 

ingestion revealed dilation of the stomach and small intestine (Carter 1966) and erosive changes of the 

gastrointestinal tract (Koppel et al. 1986). High (unspecified) levels of dietary selenium compounds have 

been implicated as causing gastrointestinal disturbances in chronically exposed humans (Smith et al. 

1936), but such symptoms are not specific to selenium intoxication. 

Exposure of pigs to feed containing 54 mg/kg selenium for 1–7 days resulted in severe toxicity and death 

of several animals. Clinical signs included anorexia and vomiting, and histological examination 

(70–79 days after exposure) of three of the exposed animals that died found lesions ranging from small 

erosions (1–2 mm diameter) to extensive mucosal necrosis (up to 100 mm diameter) near the cardia of the 

stomach (Penrith and Robinson 1996). 

Gross necropsy of steers that died after ingestion of sodium selenite revealed severe gastrointestinal 

irritation (Baker et al. 1989; Maag et al. 1960). In addition, cattle and other livestock exhibiting alkali 
SELENIUM 86 

3. HEALTH EFFECTS 

disease, perhaps as a result of long-term consumption of range plants high in selenium, ate and drank less 

and suffered from ulcers in the upper intestinal tract (Shamberger 1986). A single oral dose of 5 mg 

selenium/kg as selenite caused edema and congestion of abdominal viscera in lambs (Smyth et al. 1990). 

However, treatment of steers with selenomethionine or selenite in food at doses up to 0.808 mg 

selenium/kg/day for 120 days did not produce any changes in histology of the gastrointestinal tissues 

(O’Toole and Raisbeck 1995). 

Gastrointestinal effects were not observed in rats treated with selenite in the diet for 8 weeks at a dose of 

0.45 mg selenium/kg/day (Chen et al. 1993). Selenium treatment in drinking water for 13 weeks at doses 

up to 1.57 and 7.17 mg selenium/kg/day as selenate in rats and mice, respectively, and 1.67 and 3.83 mg 

selenium/kg/day as selenite in rats and mice, respectively, did not cause any gastrointestinal effects (NTP 

1994). Gastrointestinal effects were not observed in rats fed organic selenium (seleniferous corn or 

wheat) at 0.5 mg selenium/kg/day for 24 months (Nelson et al. 1943). Vomiting and anorexia were 

reported in monkeys receiving 0.15 mg/kg/day selenium as L-selenomethionine by oral intubation during 

gestation days 20–50 (Tarantal et al. 1991). 

Selenium sulfide administration by gavage at lethal levels has been reported to cause diarrhea and 

anorexia in rats (Cummins and Kimura 1971). No gastrointestinal effects were seen in mice administered 

464 mg selenium sulfide/kg/day or in rats administered 31.6 mg selenium sulfide/kg/day by gavage once 

daily for 13 weeks (NTP 1980c). 

Hematological Effects. Hematological changes were evaluated in a 120-day double blind study of 

healthy men who consumed a controlled diet of foods naturally low or high in selenium (Hawkes et al. 

2001). Eleven subjects were fed 0.0006 mg selenium/kg/day in the diet for 21 days (baseline period), 

followed by 0.0002 mg/kg/day (6 subjects) or 0.004 mg/kg/day (5 subjects) for the following 99 days. 

Complete blood counts (white blood cells, lymphocytes, granulocytes, platelets, erythrocytes, hematocrit) 

and hemoglobin concentration measurements showed no adverse effects of selenium supplemenation. 

Mean within-subject changes from baseline in white blood cell counts were significantly different in the 

low- and high-selenium groups at last two time points in the study (days 70 and 99). At the end of the 

study, the white blood cell counts were decreased by 5% in the high-selenium group and increased by 

10% in the low-selenium group, due mainly to changes in numbers of granulocytes. Lymphocyte counts 

were significantly increased in the high-selenium group on day 45, but not at the end of the study. There 

were no clear effects of selenium on numbers of activated or cytotoxic T-cells, lymphocyte phenotypes, 
SELENIUM 87 

3. HEALTH EFFECTS 

serum immunoglobulins, or complement fractions, as summarized in Section 3.2.2.3 (Immunological 

Effects). 

Increased prothrombin time was reported for individuals chronically exposed to estimated dietary doses 

of 0.016 mg selenium/kg/day in a high-selenium region of China (Yang et al. 1989a). However, no 

increase in prothrombin time was found in another study of individuals consuming diets that supplied up 

to 0.0098 mg/kg/day selenium (Longnecker et al. 1991). A study that compared children from 

seleniferous and nonseleniferous areas of Venezuela found slightly reduced (no statistical analysis was 

performed) hemoglobin levels and hematocrit values for the children from the seleniferous area (Jaffe et 

al. 1972). However, the children from the seleniferous zone had a poorer diet, consumed less milk and 

meat, and had a greater incidence of intestinal parasites, which may account for the differences observed. 

Red blood cell counts were significantly increased in mice that received drinking water containing 9 ppm 

(0.82 mg selenium/kg/day) selenium as sodium selenite for 14 days (Johnson et al. 2000). However, 

these mice also had a severe reduction in water consumption (43%) and this may have led to a decrease in 

blood volume. No significant increase in red blood cell count (or decrease in water consumption) was 

observed for mice receiving 3 ppm (0.38 mg selenium/kg/day) selenium as sodium selenite, or up to 

9 ppm (1.36 mg selenium/kg/day) selenium as selenomethionine for 14 days (Johnson et al. 2000). 

No hematological changes (hemoglobin concentration, hematocrit, erythrocyte count, and cell volume) 

were reported for male Sprague-Dawley rats fed diets providing up to 0.27 mg selenium/kg/day as sodium 

selenite for 40 days (Eder et al. 1995). Increased hematocrit was observed in rats treated with selenate 

(1.56 mg selenium/kg/day) or selenite (1.67 mg selenium/kg/day) in the drinking water for 13 weeks, but 

only at concentrations that decreased water intake (NTP 1994). No effects on hematology end points 

were observed in mice treated with selenate or selenite in drinking water for 13 weeks at 7.17 mg 

selenium/kg for selenate and 3.83 mg selenium/kg/day for selenite (NTP 1994). 

No differences in blood cell counts or hematological parameters were found in rabbits administered 

0.137 mg selenium/kg/day as sodium selenite in the diet for 3 months, compared with control animals 

receiving a normal laboratory diet (Turan et al. 1999b). 

A dose-related decrease in hematocrit was observed in rats fed seleniferous wheat (Halverson et al. 1966). 

Compared to controls, hemoglobin was decreased 23 and 79% at 0.32 and 0.56 mg selenium/kg/day, 

respectively. Hemoglobin reductions were most evident in the animals that had died during the 

experiments. In a 2-year cancer study, Harr et al. (1967) reported that the hemoglobin concentration 
SELENIUM 88 

3. HEALTH EFFECTS 

decreased by 0.5 g/100 mL with each 2-fold increase of sodium selenate in the diet, but did not specify 

the lowest dose at which hemoglobin concentrations were significantly reduced compared to the controls 

(the range of selenium doses used was 0.025–0.40 mg selenium/kg/day). Hematocrit was increased in 

rats given selenite and selenate in drinking water for 13 weeks at concentrations that also resulted in 

decreased water intake (NTP 1994). No hematological effects were noted in rats or mice treated with 

selenate at 0.92 and 7.17 mg selenium/kg/day, respectively, or selenite at 0.86 and 3.83 mg 

selenium/kg/day, respectively (NTP 1994). 

No studies were located regarding hematological effects in humans or other animals after oral exposure to 

selenium sulfide or selenium disulfide. 

Musculoskeletal Effects. No adverse musculoskeletal effects were reported following chronic oral 

exposure of humans to dietary levels of selenium of up to 0.0098 mg selenium/kg/day (Longnecker et al. 

1991). 

A single oral (subroute not specified) dose of sodium selenite (5 mg selenium/kg/day) caused edema in 

skeletal muscles of the diaphragm in sheep (Smyth et al. 1990). Exposure of pigs to feed containing 

54 mg/kg selenium for 1–7 days resulted in severe toxicity and death of several animals (Penrith and 

Robinson 1996). Histological examination of skeletal muscle from animals that died found damage with 

interstitial oedema and diffuse swelling of fibers. Livestock suffering from chronic alkali disease, a 

disease once common in the southwestern United States where selenium levels are high, showed lameness 

due to joint erosion and hoof deformation (Shamberger 1986). However, treatment of steers with 

selenomethionine or selenite in food at doses up to 0.808 mg selenium/kg/day for 120 days did not 

produce any changes in muscle or bone histology (O’Toole and Raisbeck 1995). Hyperplasia of the 

sarcolemma nuclei and disintegration of myofibrils were observed in the skeletal muscles of pigs fed an 

unspecified form of selenium for 34 days (Stowe et al. 1992). In a 2-year cancer study, Harr et al. (1967) 

fed graded doses of selenium in the form of sodium selenate or selenite to rats and reported frank 

osteotoxicity at doses as low as 0.2 mg selenium/kg/day given for several months (duration specified as 

less than 100 days). Selenium administered in drinking water for 13 weeks at doses up to 1.57 and 

7.17 mg selenium/kg/day as selenate in rats and mice, respectively, and 1.67 and 3.83 mg selenium/kg as 

selenite in rats and mice, respectively, failed to cause adverse musculoskeletal effects (NTP 1994). 

Musculoskeletal effects were not observed in rats fed seleniferous corn or wheat at 0.5 mg 

selenium/kg/day for 24 months (Nelson et al. 1943). No musculoskeletal effects were seen in mice 
SELENIUM 89 

3. HEALTH EFFECTS 

administered 464 mg selenium sulfide/kg/day or in rats administered 31.6 mg selenium sulfide/kg/day by 

gavage once daily for 13 weeks (NTP 1980c). 

Hepatic Effects. Limited data suggest that hepatotoxicity can occur in humans following acute oral 

exposure to sodium selenate, but no definitive studies were located regarding hepatic effects in humans 

after intermediate or chronic oral exposure to selenium compounds. Tests following an acute poisoning 

of a 15-year-old girl with sodium selenate revealed abnormally elevated serum bilirubin and alkaline 

phosphatase (Civil and McDonald 1978). Hepatic effects, such as changes in serum liver enzymes or 

liver morphology (identified by ultrasonography ), have not been observed in humans at chronic dietary 

intakes of 0.0098 mg selenium/kg/day (Longnecker et al. 1991) or 0.025 mg selenium/kg/day (Yang et al. 

1989a). Selenium-induced hepatoxicity is documented in animals as summarized below. The lack of 

evidence of liver damage in humans due to selenosis, despite the animal data to the contrary, suggests a 

problem with the animal models of the disease. 

Congestion and/or edema and hemorrhage in the liver have been reported in sheep following the acute 

oral (subroute not specified) administration of lethal levels of sodium selenate (Hopper et al. 1985) or 

sodium selenite (Smyth et al. 1990) and in mules and pigs following administration of lethal levels of 

sodium selenite (Miller and Williams 1940). A significant decrease in relative liver weight was reported 

for mice exposed to 9 ppm (0.82 mg selenium/kg/day) selenium as sodium selenite in drinking water for 

14 days, but not to 3 ppm (0.38 mg selenium/kg/day) (Johnson et al. 2000). No effect on liver weight was 

observed for mice receiving up to 9 ppm (1.36 mg selenium/kg/day) selenium as selenomethionine in 

drinking water for 14 days (Johnson et al. 2000). 

Administration of single gavage doses of selenium monosulfide to rats produced death and widespread 

hepatic necrosis in 3/6 animals dosed with 75 mg/kg, 1/2 animals dosed with 100 mg/kg, and 2/2 animals 

dosed with 125 mg/kg (Moore et al. 1996b). 

Hepatic effects have also been reported following intermediate-duration exposure in pigs, but not in 

cattle. Pigs exposed for 7 weeks to either dietary organic selenium in dried plants (either A. pruelongus or 

A. bisulcatus) or sodium selenate (at 1.1 or 1.3 mg selenium/kg/day) exhibited diffuse swelling and 

vacuolar degeneration of hepatocytes (Baker et al. 1989). The doses used in this study reduced mean 

survival to only 44 days. Pigs exposed to sodium selenite in feed for 35 days at doses less than half as 

high as those tested by Baker et al. (1989) (0.47 versus 1.1 or 1.3 mg selenium/kg/day) exhibited no liver 

damage (Mahan and Magee 1991). A study of pigs treated with 0.08, 0.33, 0.59, or 1.07 mg 
SELENIUM 90 

3. HEALTH EFFECTS 

selenium/kg/day as sodium selenite in the feed for 8 weeks found hepatic nodules/granules in two pigs 

treated with 0.59 or 1.07 mg selenium/kg/day (Mihailovic et al. (1992). The lesions were diagnosed as 

postdystrophic atrophic cirrhosis. However, only these two severely affected pigs (one from each of the 

highest dose groups of 40 animals each) were selected for histopathological examination. Hepatic effects 

were not observed in pigs fed selenium at 1.25 mg selenium/kg as organic selenium of the type(s) found 

in the plant A. bisulcatus for up to 5 days, or D,L-selenomethionine or selenate for up to 6 weeks (Panter 

et al. 1996). Treatment of steers with selenomethionine or selenite in food at doses up to 0.808 mg 

selenium/kg/day for 120 days did not produce any changes in liver weight or histology (O’Toole and 

Raisbeck 1995). 

Alterations or cirrhosis of the liver in experimental animals following intermediate or chronic oral 

exposure to selenium compounds have been reported by Bioulac-Sage et al. (1992), Fitzhugh et al. 

(1944), Halverson et al. (1970), Harr et al. (1967), Kolodziejczyk et al. (2000), Nelson et al. (1943), and 

Schroeder and Mitchener (1972). Halverson et al. (1966) reported reduced liver-to-body-weight ratios 

and increased bilirubin in rats administered 0.44 mg selenium/kg/day for 6 weeks as naturally occurring 

selenium in wheat. At this level, five of eight rats died. At a dose of 0.84 mg selenium/kg/day 

administered as sodium selenate in drinking water for 4–6 weeks, rats developed cirrhosis of the liver 

(Palmer and Olson 1974). At this level, two of six rats died. 

Hepatic damage was observed in mice exposed to 0.2 mg selenium/kg/day as sodium selenite in food for 

12 weeks (Skowerski et al. 1997a), and ultrastructural examination showed that the cytoplasm of the 

hepatocytes contained extremely large and irregularly-shaped vacuoles. Wistar rats administered 

0.324 mg selenium/kg/day as sodium selenite in food for 12–14 weeks showed degenerative changes to 

the liver (not fully described in text) (Turan et al. 1999a). Livers of rats fed 0.002 or 0.005 mg 

selenium/kg/day as sodium selenite for 3 months showed damage that increased with dose (Kolodziejczyk 

et al. 2000). Rats from the 0.002 mg selenium/kg/day group had a distinct swelling of Küpffer cells in 

dilated sinusoidal vessels, mainly in the proximity of portal fields, and occasional necrotic areas 

comprising groups of hepatocytes, while livers from rats receiving 0.005 mg selenium/kg/day showed 

activation and swelling of the Küpffer cells in widened sinusoidal vessels, relatively abundant infiltrations 

of mononuclear cells into portal canals, and sporadic areas of necrosis within individual lobules. 

Young rats treated with sodium selenite in the feed for 2 months had nodular hyperplasia at a dose of 

0.2 mg selenium/kg/day. However, clinical tests of liver function (bilirubin, alanine aminotransferase, 

aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyltransferase activities) showed no 
SELENIUM 91 

3. HEALTH EFFECTS 

significant changes (Bioulac-Sage et al. 1992). Diffuse panlobular vacuolar changes were reported in rats 

fed sodium selenite in the diet for 8 weeks at 0.45 mg/kg/day (Chen et al. 1993). 

In a 2-year cancer study, acute toxic hepatitis was common among rats fed sodium selenite or sodium 

selenate at 0.25 mg selenium/kg/day or higher (Harr et al. 1967; Tinsley et al. 1967). Liver surfaces were 

mottled, and parenchymatous degeneration was present. Hepatic lesions occurred at a dose as low as 

0.10 mg selenium/kg/day. Absolute liver weights decreased with increasing levels of sodium selenate or 

sodium selenite in the diet. The average liver weight of animals administered selenate (14.5 g) was twice 

the average liver weight of animals administered selenite (7.2 g); however, the average liver weight of 

control animals was not reported, and possible dose-related hepatic effects were not discussed by these 

authors. 

Increased serum bile acids, suggesting cholestasis, were observed in rats treated with 1.57 mg 

selenium/kg/day as sodium selenate in drinking water for 13 weeks, but no effects were noted at 

0.92 mg/kg/day (NTP 1994). In a 13-week drinking water study, hepatic effects were not observed in 

mice treated with sodium selenate at 7.17 mg selenium/kg/day, in mice treated with sodium selenite at 

doses up to 3.83 mg selenium/kg/day, or in rats treated with sodium selenite at doses up to 1.67 mg 

selenium/kg/day (NTP 1994). Increased serum aspartate aminotransferase and alanine aminotransferase 

activities were observed in mice treated by gavage with selenocystine at doses of 9.4 mg selenium/kg/day 

for 30 days (Sayato et al. 1993) or 4.7 mg selenium/kg/day for 90 days (Hasegawa et al. 1994). No 

effects on liver enzymes were observed in mice treated with selenocystine at 4.7 mg selenium/kg/day for 

30 days (Sayato et al. 1993) or at 2.5 mg selenium/kg/day for 90 days (Hasegawa et al. 1994). Chronic 

dietary administration of selenium as seleniferous corn or wheat at doses ranging from 0.25 to 

0.50 mg/kg/day for 24 months produced cirrhosis of the liver in rats (Nelson et al. 1943). 

An increased incidence of amyloidosis of the major organs, including the liver, was observed in mice 

following lifetime exposure to sodium selenate or sodium selenite in drinking water at a level of 0.57 mg 

selenium/kg/day (Schroeder and Mitchener 1972). This effect was noted in 30% of control mice and 58% 

(p<0.001) of selenium-treated mice. Data for individual organs were not provided. 

Selenium sulfide administered to rats daily by gavage for 13 weeks produced focal coagulation necrosis 

in the liver with infiltration by inflammatory cells. These changes developed at a dose of 31.6 mg 

selenium sulfide/kg/day, but not at a dose of 17.8 mg selenium sulfide/kg/day (NTP 1980c). In mice, on 
SELENIUM 92 

3. HEALTH EFFECTS 

the other hand, oral intubation of selenium sulfide at 464 mg selenium sulfide/kg/day did not produce 

hepatic effects (NTP 1980c). 

Renal Effects. No studies were located regarding renal effects in humans after oral exposure to 

selenium or selenium compounds. 

In domestic and experimental animals, renal effects have been observed following both acute and chronic 

oral exposures to selenium compounds. Administration of a single oral (subroute not specified) dose of 

sodium selenite at 5 mg selenium/kg/day produced hydropic degeneration of the kidney in sheep (Smyth 

et al. 1990). In a study of the toxicity of L-selenomethionine to long-tailed macaques by nasogastric 

intubation, two animals administered 0.24 mg selenium/kg/day aspirated vomitus secondary to emesis, 

developed obvious gastritis, and died of anorexia, one after 10 days and the other after 15 days of 

administration (Cukierski et al. 1989). Histopathologic examination of the kidneys of these animals 

revealed glomerulonephritis and proximal convoluted tubule nephropathy. The study authors indicated 

that these changes were consistent with macaque fatal fasting syndrome and may not have resulted from 

the direct effects of L-selenomethionine. Following long-term ingestion of plants high in selenium, 

livestock suffering from alkali disease exhibited nephritis (Shamberger 1986). However, treatment of 

steers with selenomethionine or selenite in food at doses up to 0.808 mg selenium/kg/day for 120 days did 

not produce any changes in kidney weight or histology (O’Toole and Raisbeck 1995). 

A dose-related increase in degeneration of the renal papilla (described as mild to minimal) was observed 

in rats treated with selenate or selenite in the drinking water at about 0.5 mg selenium/kg/day for 

13 weeks (NTP 1994). No evidence of renal toxicity was observed in rats given 0.3 mg selenium/kg/day 

in this study. In contrast to rats, the only kidney effect noted in mice treated with sodium selenate or 

selenite in the drinking water was increased relative kidney weight (NTP 1994). This effect, which 

occurred at 1.87  mg selenium/kg/day as selenate and 1.61 mg selenium/kg/day as selenite, was only noted 

at doses at which drinking water intake was decreased, leading the investigators to suggest that the effect 

may have been a result of dehydration. A similar increase in relative kidney weight associated with 

decreased water consumption was observed in mice consuming approximately 0.38 mg selenium/kg/day 

as selenite in drinking water, but no effect on kidney weight or water consumption was observed in mice 

consuming up to 1.36 mg selenium/kg/day as selenomethionine (Johnson et al. 2000). No renal effects 

were observed in pigs fed selenium at 1.25 mg selenium/kg as organic selenium found in the plant A. 

bisulcatus for up to 5 days, or D,L-selenomethionine or selenate for up to 6 weeks (Panter et al. 1996). 

No effects on the kidneys were observed in rats treated with selenite in the diet for 8 weeks at a dose of 
SELENIUM 93 

3. HEALTH EFFECTS 

0.45 mg selenium/kg/day (Chen et al. 1993). Gavage treatment of mice with selenocystine for 30 days at 

a dose of 9.4 mg selenium/kg/day had no adverse effect on the kidneys (Sayato et al. 1993). 

Rats chronically fed selenite in the diet were reported to exhibit more frequent and more severe nephritis 

than those given equivalent amounts of selenate (Harr et al. 1967); however, the study authors did not 

quantify these observations or statistically compare data from the two groups. An increased incidence of 

amyloidosis of the major organs, including the kidneys, was observed in mice following lifetime exposure 

to sodium selenate or sodium selenite in drinking water at a level of 0.57 mg selenium/kg/day (Schroeder 

and Mitchener 1972). This effect was noted in 30% of control mice and 58% (p<0.001) of seleniumtreated mice. Data for individual organs were not provided. 

A mixture of selenium sulfide and selenium disulfide administered to mice daily by gavage for 13 weeks 

at a dose of 464 mg selenium sulfides/kg/day produced an increase in the incidence and severity of 

interstitial nephritis compared with the controls, whereas a daily dose of 216 mg selenium sulfides/kg did 

not elicit renal toxicity (NTP 1980c). In rats, selenium sulfide by oral intubation at 31.6 mg selenium 

sulfides/kg/day for 13 weeks did not produce renal effects (NTP 1980c). 

Endocrine Effects. A balance in selenium and iodine levels is needed for normal thyroid hormone 

metabolism. Selenium is an essential component of the iodothyronine 5'-deiodinase enzymes, which 

convert the prohormone thyroxine (T4) to the active form, triiodothyronine (T3) (Delange 2000; Köhrle 

1994; St Germain and Galton 1997). Selenium is also a component of glutathione peroxidase (GPX), the 

main enzyme responsible for protecting thyroid cells against oxidative damage. Selenium deficiency 

causes decreases in metabolic clearance of iodothyronines, extrathyroidal production of T3, and thyroid 

iodine concentrations in experimental animals (Arthur and Beckett 1989, 1994; Behne and Kyriakopolous 

1993). Deficiency in both selenium and iodine has been associated with goiter and cretinism in humans 

and causes thyroid gland necrosis and fibrosis in rats (Delange 2000; Goyens et al. 1987; Vanderpas et al. 

1990). Additional information on thyroid effects of selenium and iodine deficiency is discussed in 

Section 3.9. Thyroid hormone levels in humans and animals can also be affected by selenium 

supplementation; these effects include decreases in serum T3 and T4 levels and increases in serum TSH 

levels, suggesting suppression of thyroid hormone production, as discussed below. 

A limited amount of information is available regarding endocrine effects in humans following oral 

exposure to selenium. Serum levels of thyroid and reproductive hormones were evaluated in a double 

blind 120-day study of healthy men (20–45 years old) who consumed a controlled diet of foods naturally 
SELENIUM 94 

3. HEALTH EFFECTS 

high or low in selenium (Hawkes and Turek 2001). Eleven subjects were fed 0.0006 mg/kg/day of 

selenium in the diet for the first 21 days of the study, followed by 0.0002 μg selenium/kg/day (6 subjects) 

or 0.004 mg selenium/kg/day (5 subjects) for 99 days. Blood samples were analyzed for serum levels of 

selenium, thyroid hormones (T3 and TSH), and reproductive hormones (testosterone, follicle-stimulating 

hormone, luteinizing hormone, prolactin, estradiol, and progesterone) during week 3 (baseline), week 

17 (ending value), and at several interim time points. 

Selenium levels in blood plasma began to change within 3 days of starting the low- and high-selenium 

diets and progressively continued throughout the study (Hawkes and Turek 2001). By week 17, mean 

plasma selenium concentrations had increased by 109% in the high-selenium group and decreased by 

38.5% in the low-selenium group. Group mean serum T3 concentrations (averages of within-subject 

changes from baseline) were significantly different in the low-selenium subjects and high-selenium 

subjects at all time points, but the changes are insufficient to be considered adverse as discussed below. 

In the low-selenium group, serum T3 levels increased an average of 14 and 8% from baseline at weeks 

8 and 17, respectively. In the high-selenium group, serum T3 levels decreased an average of 23 and 11% 

from baseline at weeks 8 and 17, respectively. Analysis of variance (ANOVA) showed a significant main 

effect of dietary selenium on serum T3 concentrations, as well as a significant selenium x time interaction, 

indicating that the changes in T3 levels decreased over time. Although the decreases in serum T3 in the 

high-selenium group and increases in serum T3 in the low-selenium group lessened in magnitude during 

the study, all group mean values appear to have remained within the normal range. The baseline and 

week 17 serum total T3 values (mean±SD) were 1.82±0.36 and 1.57±0.07 nmol/L in the high-selenium 

group, and 1.57±0.25 and 1.64±0.16 nmol/L in the low-selenium group, compared to the normal human 

range of 1.1–2.7 nM/L (Stockigt 2000), indicating that the changes in serum T3 were subclinical and not 

toxicologically significant. Serum TSH concentrations increased significantly by 32% over its baseline 

concentration in the high-selenium group, but did not change significantly in the low-selenium group. 

Baseline and ending mean TSH values in the high-selenium group were 2.25±0.81 and 2.96±1.05 mU/L, 

respectively, both of which are in the normal range of 0.3–4.0 mU/L (Stockigt 2000). The lack of 

clinically significant changes in serum T3 and TSH values is not surprising because the study was 

designed as a nutritional study and not as a toxicological study; the selenium intakes bracketed the current 

recommended dietary allowance (RDA) (~0.8 μg Se/kg/day) and were well below the tolerable upper 

limit level (~5.7 μg Se/kg/day) recommended by the Food and Nutrition Board (NAS 2000). There were 

no significant changes in serum levels of free or total testosterone, follicle-stimulating hormone, 

luteinizing hormone, prolactin, estradiol, or progesterone. This study also found no adverse immunologic 

or male reproductive changes as summarized in Sections 3.2.2.3 and 3.2.2.5. 
SELENIUM 95 

3. HEALTH EFFECTS 

An examination of thyroid hormone levels in lactating women residing in areas of Venezuela with high 

levels of selenium in the soil (selenium intake ranged from 250 to 980 μg per day as estimated from 

selenium content of breast milk) revealed a significant decrease in serum T3 levels, as compared with 

women having normal selenium intakes (90–350 μg/day), but these hormone levels remained within the 

normal range (Brätter and Negretti De Brätter 1996). Additionally, a significant inverse correlation for 

selenium and serum T3 concentration was found using the Spearman Rank test. The study authors noted 

that the effect of selenium on T3 levels became significant at dietary intake levels of 350–450 μg/day. No 

significant alterations in serum T4 or TSH levels or correlations with selenium intake were found. 

Twenty weeks of selenium supplementation (10, 20, 30, or 40 μg/day) of New Zealanders who normally 

consume a diet low in selenium (unsupplemented intake of 28–29 μg/day), but show no signs of 

deficiency, produced a reduction in T4 concentration in all groups (Duffield et al. 1999). However, only 

the differences between the 10 μg-group and controls and the combined supplemented individuals and 

controls were significant. T3 and TSH levels were not measured. Thyroglobulin concentration did not 

change significantly with supplementation. 

In a study of 68 male Latvian fish consumers (Hagmar et al. 1998), a significant inverse correlation was 

found between serum levels of selenium and TSH. No correlation was found between serum selenium 

concentration and the serum concentrations of T3 or T4. No measurements were made of dietary selenium 

intake. 

Selenium supplementation has been shown to affect type-I-deiodinase activity in male rats (Behne et al. 

1992; Eder et al. 1995; Hotz et al. 1997). Exposure to 0.055 or 0.27 mg selenium/kg/day as sodium 

selenite in food for 40 days produced a significant decrease (approximately 50%) in serum levels of T3 

and a nonsignificant reduction in type-I-deiodinase activity compared with rats receiving 0.009 or 

0.026 mg selenium/kg/day (Eder et al. 1995). Exposure to 0.27 mg selenium/kg/day did not produce any 

other adverse signs, such as weight loss or decreased food consumption, and serum T4 levels were similar 

in all groups. 

Exposure of weanling male Sprague-Dawley rats to 0.09 mg selenium/kg/day as sodium selenate in food 

for 6 weeks produced a significant (~30%) increase in TSH, compared with controls receiving 0.009 mg 

selenium/kg/day (Hotz et al. 1997). Serum T3 and T4 levels and thyroid glutathione peroxidase levels 

were unaffected by dietary selenium. Kidney type-I-deiodinase levels were decreased (~10%) in high 
SELENIUM 96 

3. HEALTH EFFECTS 

selenium animals compared with controls, but the differences were not significant, and liver type-Ideiodinase levels were unaffected by dietary selenium. Iodine-deficient diets produced greater thyroid 

glutathione peroxidase activity at each dietary level of selenium, and the greatest activity was in rats with 

high selenium. 

No significant changes in thyroid levels of T3 or T4 were found in male Wistar rats fed diets containing 

high selenium (0.105 mg selenium/kg/day as sodium selenite or 0.118 mg selenium/kg/day as 

L-selenomethionine) for 3 months, compared with controls receiving adequate selenium (0.0015 mg 

selenium/kg/day as sodium selenite) (Behne et al. 1992). However, rats eating the high selenium diet 

showed a significant reduction in hepatic type I deiodinase activity, compared with controls, with a 29% 

reduction in the production rate of T3 from T4 and a 45% reduction in the production rate of 

3,3’-diiodothyronine from T4. 

Many studies have documented reduced body weight gain in young animals treated with selenium 

compounds, and abnormal weight loss in older animals (Grønbaek et al. 1995; Halverson et al. 1966; Harr 

et al. 1967; Jacobs and Forst 1981a; Johnson et al. 2000; Nelson et al. 1943; NTP 1994; Palmer and Olson 

1974; Panter et al. 1996; Schroeder 1967; Tarantal et al. 1991; Tsunoda et al. 2000). There is evidence to 

suggest that these effects may be due in part to the interactions of selenium or selenium compounds with 

hormones that regulate normal growth and body weight. In a 14-day study suggesting that selenium may 

inhibit pituitary function, Thorlacius-Ussing (1990) treated nursing rats with sodium selenite in drinking 

water (0.64 or 0.96 mg/kg/day). The resulting decrease in the body weight gain of the pups observed at 

both doses may be associated with a reduction in somatomedin C levels (no other hormone levels were 

tested), and the weight deficiency could be reversed by administration of a growth hormone. 

Postweanling female Wistar rats treated with sodium selenite (0.64 mg selenium/kg/day) in drinking 

water for 3 or 6 weeks exhibited decreased weight gain and decreased somatomedin C serum 

concentrations. When the selenium supplement was removed after 3 weeks, body weight gain returned to 

normal, but the serum somatomedin C concentrations did not return to control levels. Growth hormone 

secretion in response to growth hormone releasing factor was also reduced in the selenium-exposed group 

(Thorlacius-Ussing et al. 1988). Serum somatomedin C levels were not significantly different among 

three exposure categories (<200, 201–240, and >240 ng selenium/mL) in 44 long-term residents of 

seleniferous areas in South Dakota, despite >50% differences in serum, whole blood, and toenail selenium 

levels among the groups (Salbe et al. 1993). A 10% reduction in body weight and a reduction in tibia 

lengths, compared to pair-fed controls, were found in rats provided with sodium selenite in the drinking 

water at 0.46 mg selenium/kg/day for 35 days (Grønbaek et al. 1995). A significant reduction in insulin­
SELENIUM 97 

3. HEALTH EFFECTS 

like growth factor-binding protein-3 was also noted. The investigators concluded that the reduction in 

growth caused by excess selenium is not due to reduced caloric intake. 

Selenium administered in drinking water for 13 weeks at doses up to 1.57 and 7.17 mg selenium/kg/day 

as selenate in rats and mice, respectively, and 1.67 and 3.83 mg selenium/kg as selenite in rats and mice, 

respectively, failed to cause changes in the weights or histology of the thyroid, adrenal glands, 

parathyroid, or pancreas (NTP 1994). 

Lambs given a single oral (subroute not specified) dose of 5 mg selenium/kg as sodium selenite exhibited 

cytoplasmic flocculation of the pancreas (Smyth et al. 1990). Increased pancreas weights were observed 

in rats fed organic selenium (seleniferous wheat) at a dose of 0.4 mg selenium/kg/day for 6 weeks 

(Halverson et al. 1966). Chronic exposure of rats fed sodium selenite or sodium selenate in their diet for 

a lifetime was associated with pancreatic damage. Although Harr et al. (1967) reported a dose-related 

increase in the incidence and severity of pancreatic lesions in treated rats, they did not specify the lowest 

dose at which pancreatic lesions were observed. 

Treatment of steers with selenomethionine or selenite in food at doses up to 0.808 mg selenium/kg/day 

for 120 days did not produce any changes in weight or histology of the pancreas, adrenal glands, thyroid, 

or pituitary gland (O’Toole and Raisbeck 1995). 

An increased incidence of amyloidosis of the major organs, including the adrenal gland, was observed in 

mice following lifetime exposure to sodium selenate or sodium selenite in drinking water at a level of 

0.57 mg selenium/kg/day (Schroeder and Mitchener 1972). This effect was noted in 30% of control mice 

and 58% (p<0.001) of selenium-treated mice. Data for individual organs were not provided. 

Dermal Effects. Jensen et al. (1984) described both marked alopecia and the deformity and loss of 

fingernails in a woman who had consumed a selenium supplement containing 31 mg total selenium (in 

the form of sodium selenite and elemental selenium) per tablet for 77 days. The woman consumed one 

tablet each day in addition to vitamin supplements (vitamins C, A, D, E, B complex) and a mineral 

supplement "labeled as containing all 72 trace elements in undefined quantities." In epidemiological 

studies of populations chronically exposed to high levels of selenium in food and water, investigators 

have reported discoloration of skin, pathological deformity and loss of nails, loss of hair, and excessive 

tooth decay and discoloration (Smith et al. 1936; Yang et al. 1983, 1989a, 1989b). The 1989 studies by 

Yang et al. follow up their original 1983 study of Chinese populations living in areas classified as having 
SELENIUM 98 

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low-, medium-, and high-selenium exposure based on local soils and food supplies. The average and 

standard error of selenium intakes in the low-, medium-, and high-intake regions were 0.0012±0.00009, 

0.0037±0.0004, and 0.025±0.001 mg/kg/day, respectively. The whole blood (average ± standard error) 

concentrations of selenium in the low-, medium-, and high-intake regions were 0.16±0.00, 0.35±0.02, and 

1.51±0.05 mg/L, respectively. The estimated daily dietary selenium intake required to produce these 

symptoms in an area of China characterized by endemic selenosis was at least 0.016 mg selenium/kg/day 

(Yang et al. 1989a). This corresponds to a blood concentration of 1.054 mg/L and an estimated daily 

intake of 0.91 mg/day, assuming a 55-kg Chinese man or woman and using the regression analysis 

provided by Yang et al. (1989b). The NOAEL from the highest intake population not affected by nail 

disease is 0.015 mg selenium/kg/day, which corresponds to a blood concentration of 0.97 mg/L. Foods 

that contributed the greatest levels of selenium were smoked pork, coal-dried corn, chestnuts, pumpkin 

seeds, dried fruits, and garlic. It has been noted that the selenosis problem in China began when coal with 

high levels of selenium was burned as the main source of fuel (Whanger 1989). Food was cooked and 

dried over the open flame, adding selenium to the food. In addition, the people breathed large amounts of 

smoke, but the contribution of volatilized selenium to the total dose of selenium has not been adequately 

characterized (Whanger 1989). Coal was also burned on the fields as a fertilizer source. Environmental 

selenium concentrations in the low-, medium-, and high-intake regions were 0.37–0.48, 0.73–5.66, and 

7.06–12.08 mg/kg in soil, and 370, 1,720, and 12,270 μg/L in water, respectively (Yang et al. 1989b). 

No evidence of nail disease was observed in a population living on selenium-rich ranches in the western 

United States (Longnecker et al. 1991). Doses of selenium were calculated to be between 0.001 and 

0.01 mg/kg/day, corresponding to a maximum intake of 0.724 mg/day. Whole blood selenium 

concentrations were 0.18–0.67 mg/kg. Although these values for the United States are consistent with 

studies of the Chinese population, only one or a few individuals ingested the highest doses. 

The highest selenium intake for villagers in a high-selenium area of China in which endemic selenosis did 

not occur was estimated at 1.51 mg selenium/person/day (0.027 mg selenium/kg/day), with the average 

dietary selenium intake in this area of selenosis occurrence estimated to be 3.2 mg selenium/person/day 

(0.058 mg selenium/kg/day) (Yang et al. 1983). The lowest daily dietary selenium intake associated with 

dermal effects, 0.91 mg selenium/day, was converted to equivalent daily doses from food 

(0.016 mg/kg/day) for presentation in Table 3-2. 

Five individuals from the high selenium region of China described by Yang et al. (1989a) who had been 

diagnosed with overt signs of selenosis (hair loss and nail sloughing) in 1986 were reexamined in 1992 
SELENIUM 99 

3. HEALTH EFFECTS 

(Yang and Zhou 1994). The results of this examination showed that these individuals had recovered from 

selenosis (overt symptoms of nail sloughing were absent) and that the average selenium concentrations in 

their blood had fallen from 1,346 to 968 μg/L. The corresponding dietary intakes of selenium were 

1,270 and 819 μg/day. This study has been used to establish a LOAEL of 0.023 mg selenium/kg/day and 

a NOAEL of 0.015 mg selenium/kg/day. Based on the occurrence of these dermal effects, a chronic oral 

MRL of 0.005 mg selenium/kg/day has been derived from the NOAEL, as described in the footnote in 

Table 3-2 and detailed in Appendix A. This MRL is approximately 6 times greater than the NAS (2000) 

RDA for selenium of 55 μg/day (~0.0008 mg/kg/day). 

In a 30-day study of oral administration of L-selenomethionine to long-tailed macaques, skin lesions 

appeared on the forearm of one of two macaques given 0.01 mg selenium/kg/day. However, the limited 

number of animals precludes identifying the dose as a LOAEL for dermal effects (Cukierski et al. 1989). 

Pigs receiving dietary administration of the same doses of selenium for 35 days exhibited hoof cracking 

(Mahan and Magee 1991). Symmetrical hair loss, dry scaling skin, and cracked overgrown hooves were 

observed in one of five pigs and three of five pigs fed sodium selenate or D,L-selenomethionine at a dose 

of 1.25 mg selenium/kg/day for up to 6 weeks, respectively (Panter et al. 1996). In an experiment limited 

to a duration of 5 days because of severe paralysis, similar dermal effects were not observed in pigs fed 

1.25 mg selenium/kg/day as selenium contained in the plant A. bisulcatus. The form of selenium in 

A. bisulcatus is unknown, although Panter et al. (1996) indicate that it is nonprotein. 

Exposure of pigs to feed containing 54 mg/kg selenium for 1–7 days resulted in severe toxicity and death 

of several animals; however, none of the pigs developed coronitis or hoof separation (Penrith and 

Robinson 1996). Skin from four pigs with alopecia was examined about a month after exposure and was 

found to have epidermal thickening due to acanthosis and hyperkeratosis, vacuolar degeneration of the 

basal cells and acanthocytes, necrosis of individual keratinocytes, and serocellular crusts. 

In the late 19th and the early 20th century, livestock grazing on plants growing on seleniferous soils in 

areas of the Great Plains of the United States suffered from alkali disease attributed to the high selenium 

content of some plants. Alkali disease in horses, cattle, and swine is characterized by alopecia, inflammation at the coronary band, followed by cracked or malformed hooves and rough hair coat (Draize and 

Beath 1935). Daily selenium intakes associated with these effects were not quantified. However, 

treatment of steers with selenomethionine in food at doses of 0.288 mg selenium/kg body weight/day or 

selenite at doses of 0.808 mg selenium/kg/day for 120 days produced hoof lesions (O’Toole and Raisbeck 

1995). In intermediate-duration studies, cracked hoof walls have been observed in pigs fed selenate, 
SELENIUM 100 

3. HEALTH EFFECTS 

selenite, or an unspecified form of selenium at doses of 0.25 mg selenium/kg/day and greater (Baker et al. 

1989; Mahan and Magee 1991; Mihailovic et al. 1992; Wahlstrom and Olson 1959b). Poor quality of the 

hair coat has also been reported in mice administered sodium selenite or selenate in the diet at 0.57 mg 

selenium/kg/day (Schroeder and Mitchener 1972). Exposure of female BALB/c mice to 0.21 mg 

selenium/kg/day for 6 months from diets containing selenium as sodium selenite resulted in alopecia 

around the nose (Boylan et al. 1990). 

No studies were located regarding dermal effects in humans or other animals after oral exposure to 

selenium sulfide or selenium disulfide. 

Ocular Effects. A case-control study using a hospital discharge register indicated that there was no 

correlation between low serum selenium concentrations and cataract occurrence in humans (Knekt et al. 

1992). Since this is a case-control study, it does not provide information on the potential dietary factors, 

exposure to specific selenium compounds, or duration of exposure. 

Treatment of steers with selenomethionine or selenite in food at doses up to 0.808 mg selenium/kg/day 

for 120 days did not produce any changes in the histology of the eyes (O’Toole and Raisbeck 1995). 

Selenium given to rats and mice in drinking water for 13 weeks at up to 1.6 and 7.2 mg selenium/kg as 

selenate, respectively, or 1.7 and 3.8 mg selenium/kg as selenite, respectively, did not cause any ocular 

effects (NTP 1994). 

Body Weight Effects. Two studies reported body weight effects in humans after oral exposure to 

selenium. Selenium intake was found to affect body weight in a study of 11 men (20–45 years old) who 

were fed 0.0006 mg/kg/day of selenium in the diet for the first 21 days of the study, followed by diets 

naturally low (0.0002 μg selenium/kg/day, 6 subjects) or high (0.004 mg selenium/kg/day, 5 subjects) for 

99 days at 2,800 kcal/day (Hawkes and Keim 1995). Despite minor adjustments of intake to maintain 

body weight, by the 6th week, the high selenium group started to gain weight relative to the low selenium 

group, and the difference between the two groups became significant after the 10th week. A similar 

increase in lean body mass was observed in both groups. The study was designed as a nutritional study 

and not as a toxicological study, as the selenium intake levels were well below the tolerable upper limit 

level (~5.7 μg Se/kg/day) recommended by the Food and Nutrition Board (NAS 2000). The weight gain 

observed in this study therefore has nothing to do with weight loss due to selenosis. 
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A study that compared children from seleniferous and nonseleniferous areas of Venezuela found slightly 

reduced height and weight (no statistical analysis was performed) for the children from the seleniferous 

area (Jaffe et al. 1972). However, the children from the seleniferous zone had a poorer diet, consumed 

less milk and meat, and had a greater incidence of intestinal parasites, which may account for the 

differences observed. 

In contrast, reduced growth rates of young animals and reduced body weight in older animals are 

common observations associated with oral administration of excess sodium selenate, sodium selenite, or 

organic selenium compounds to experimental animals (Boylan et al. 1990; Cukierski et al. 1989; 

Donaldson and McGowan 1989; Grønbaek et al. 1995; Halverson et al. 1966; Harr et al. 1967; Hasegawa 

et al. 1994; Johnson et al. 2000; Nelson et al. 1943; NTP 1994, 1996; Palmer and Olson 1974; Panter et 

al. 1996; Penrith and Robinson 1996; Raisbeck et al. 1996; Sayato et al. 1993; Schroeder 1967; Tarantal 

et al. 1991; Thorlacius-Ussing 1990, Tsunoda et al. 2000; Turan et al. 1999a). This reduction in growth is 

often accompanied by reduced food and water consumption, and in dietary or drinking water studies, may 

be an effect of poor palatability of selenium compounds. However, reduced growth has also been 

observed in gavage studies (Cukierski et al. 1989; Hasegawa et al. 1994; Sayato et al. 1993) and, as 

discussed under endocrine and neurological effects, the growth retardation may have an endocrine or 

neurotransmitter component. Selenium effects on the levels of thyroid hormones (Behne and 

Kyriakopoulos 1993; Behne et al. 1992; Eder et al. 1995; Hotz et al. 1997), dopamine metabolites 

(Tsunoda et al. 2000), insulin-like growth factor–binding protein-3 (Grønbaek et al. 1995), and 

somatomedin C (Thorlacius-Ussing 1990) have been observed in selenium-treated animals, although 

somatomedin C was not a sensitive end point in humans from a high selenium area of South Dakota 

(Salbe et al. 1993). 

Other Systemic Effects. Urinary excretion of selenium was about twice as great in children with a 

high incidence of dental caries than in children with a low incidence of caries (Hadjimarkos 1969b). 

Possible confounding factors (e.g., fluoride status and socioeconomic status) were not considered, 

however. In Yang et al. (1989a), the incidence of mottled teeth in the medium- and high-selenium groups 

was increased, but the effect was attributed to interactions between selenium and fluoride. 
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3. HEALTH EFFECTS 

3.2.2.3 Immunological and Lymphoreticular Effects 

No studies were located regarding adverse immunologic or lymphoreticular effects in humans after oral 

exposure to selenium or selenium compounds. Immune system effects were evaluated in a 120-day 

double blind study of healthy men who ingested a controlled diet of foods naturally low or high in 

selenium (Hawkes et al. 2001). Eleven subjects were fed 0.0006 mg selenium/kg/day in the diet for 

21 days (baseline period), followed by 0.0002 mg/kg/day (6 subjects) or 0.004 mg/kg/day (5 subjects) for 

the following 99 days. The results show that the high-selenium diet was not immunotoxic and had some 

mild and transient immune-enhancing properties. There is an indication that selenium supplementation 

increased the secondary immune response to diphtheria vaccine when rechallenged at the end of the 

study. The mean within-subject ratio of diphtheria antibody titers 14 days after reinoculation (day 116) to 

titers 14 days after the initial challenge at baseline (day 19) was significantly greater in the high-selenium 

group than in the low-selenium group (2.7±1.8-fold vs. 0.9±0.6-fold, p=0.03). Lymphocyte counts were 

significantly increased in the high-selenium group on day 45, but not at the end of the study, and there 

were no clear effects of selenium on numbers of activated or cytotoxic T-cells. The proliferative response 

of peripheral lymphocytes to stimulation with pokeweed mitogen (a B-cell mitogen) was significantly 

higher in the high-selenium group than in the low-selenium group on days 45 and 72, although not at the 

end of the study. There was no selenium-induced lymphocyte proliferation in response to T-cell mitogens 

(phytohemagglutinin or concanavalin A), or changes in lymphocyte phenotypes, serum immunoglobulins 

(IgA, IgG, IgM), complement fractions, natural-killer cell activity, delayed-type hypersensitivity skin 

responses to seven recall antigens (tuberculin purified-protein derivative, mumps, tetanus toxoid, candida, 

trichophyton, streptokinase strepase, and coccidioidin), or antibody responses to diptheria-tetanus and 

influenza vaccines. This study was designed as a nutritional study and not as a toxicological study, as the 

selenium intake levels were well below the tolerable upper limit level (~5.7 μg Se/kg/day) recommended 

by the Food and Nutrition Board (NAS 2000). 

Other human studies also indicate that selenium contributes to enhancing immune function (Baum et al. 

1997; Kiremidjian-Schumacher et al. 1994; Peretz et al. 1991). Lymphocyte response was enhanced by 

dietary selenium, as measured by the T-lymphocyte proliferative response to pokeweed mitogen in elderly 

people taking a selenium-enriched yeast supplement (0.0014 mg/kg/day for 6 months) (Peretz et al. 

1991). This finding is similar to results of the Hawkes et al. (2001) study summarized above, although it 

was noted that the elderly as a group generally tend to have both lower blood selenium concentrations and 

lower lymphocyte proliferation than the general population. Dietary supplementation with approximately 

0.001 mg selenium/kg/day (as sodium selenate) for 8 weeks caused increased proliferation of active T 
SELENIUM 103 

3. HEALTH EFFECTS 

cells in a group of 11 volunteer subjects (Kiremidjian-Schumacher et al. 1994). The lymphocytes in the 

exposed subjects had an increased response to stimulation with alloantigen and developed into cytotoxic 

lymphocytes capable of destroying tumor cells. There was a 118% increase in cytotoxic lymphocytemediated tumor cytotoxicity, as well as an 82.3% increase in natural killer cell activity, compared to 

baseline values. The selenium supplementation regimen used in this study did not cause significant 

increases in selenium levels in the plasma or red blood cells. 

Immune function was evaluated in 40 volunteers from a Finnish population with low blood selenium 

concentrations that were supplemented with selenium or placebo for 11 weeks (Arvilommi et al. 1983). 

At the end of the supplementation period, plasma selenium levels were 74 μg/L in the placebo group and 

169 μg/L in the supplemental group. Intracellular killing of Staphylococcus aureus by granulocytes was 

slightly lower in the placebo group than in the selenium group (77.2% compared to 85.2%, p<0.05). No 

significant changes were observed in phagocytosis, chemotactic factor generation, antibody or leukocyte 

migration inhibitory factor production by lymphocytes, or proliferative responses to the T-cell mitogens 

phytohemagglutinin or concanavalin A. 

There is evidence that selenium has a role in protecting patients with HIV virus. Immune parameters and 

nutrients known to affect immune function were evaluated at 6-month intervals in 125 HIV-1-seropositive 

drug-using men and women (Baum et al. 1997). When all factors that could affect survival were 

considered jointly, only reduced number of CD4 helper T cells over time and selenium deficiency were 

significantly associated with mortality. Low plasma selenium (<85 μg/L) represented a significantly 

greater risk factor for mortality than low helper T cell counts, and conferred a more significant risk than 

any other nutrient studied, indicating that selenium-deficient HIV patients were more likely to die from 

HIV infection than those with adequate levels of selenium. 

Studies of mice, rats, and cattle suggest that exposure to high doses of sodium selenite, but not 

selenomethionine, may reduce immunological responses (Johnson et al. 2000; Koller et al. 1986; 

Raisbeck et al. 1998; Yaeger et al. 1998). BALB/c mice (five males/group) were exposed to drinking 

water containing 0, 1, 3, and 9 ppm selenium as sodium selenite (0.024, 0.17, 0.38, and 0.82 mg 

selenium/kg/day) or seleno-L-methionine (0.024, 0.17, 0.47, and 1.36 mg selenium/kg/day) for 14 days 

(Johnson et al. 2000). The mice exposed to sodium selenite showed significant decreases in the relative 

spleen weight at 9 ppm and the relative thymus weight at 3 and 9 ppm. The number of splenocytes in the 

spleens of the 9 ppm group was reduced by 62%. Single-cell splenocyte cultures were made from the 

spleens of treated animals and used to determine the effects of selenium treatment on mitogen-induced 
SELENIUM 104 

3. HEALTH EFFECTS 

lymphocyte blastogenesis and cytokine production. Cultured splenic lymphocytes from mice exposed to 

9 ppm selenium as sodium selenite showed a significant (260%) increase in the basal rate of proliferation 

and a nonsignificant increase in mitogen-induced proliferation. Exposure to 9 ppm selenium as sodium 

selenite also produced a significant increase in the amount of tumor necrosis factor α (TNFα) and 

interleukin-1β (IL-1β) produced by lipopolysaccharide (LPS)-stimulated splenic macrophages. However, 

the results of this experiment must be interpreted with caution as treatment with 9 ppm selenium as 

sodium selenite also produced a large and statistically significant decrease in food (21%) and water (43%) 

consumption, so that some of the effects observed (e.g., changes in organ weights) may reflect effects of 

dehydration rather than selenium toxicity. In contrast, the similar groups of mice treated with up to 9 ppm 

selenium as seleno-L-methionine (up to 1.36 mg selenium/kg/day)showed no significant changes in body 

weight gain, organ weights, water consumption, or food consumption compared with controls. There 

were no changes in the basal or mitogen-stimulated lymphocyte proliferation following treatment with 

seleno-L-methionine, and no alteration in the production of TNFα or IL-1β from splenic macrophages 

was observed. 

Another study in BALB/c mice examined the effects of consumption for 47 days of drinking water 

containing 7 ppm selenium as selenocystine, selenomethionine, or sodium selenite on immune function 

(Raisbeck et al. 1998). On the 14th day of the experiment, the mice received a subcutaneous injection of 

ovalbumin (OVA). Examination of mitogen-stimulated blastogenesis, B-cell function, and IgG 

concentrations at the end of the experimental period showed a significant decrease in B-cell function for 

mice treated with the two organic forms of selenium and a significant reduction in the concentration of 

OVA-specific antibodies for animals treated with any of the three forms of selenium. Total IgG 

concentration and OVA-stimulated blastogenesis did not vary between groups. 

Rats given sodium selenite in drinking water at 0.7 mg selenium/kg/day for 10 weeks exhibited reduced 

humoral antibody (IgG) production in response to an administered antigen, and reduced prostaglandin 

synthesis, but there was no effect on natural killer cell (NKC) cytotoxicity (Koller et al. 1986). At lower 

doses (0.07 or 0.28 mg selenium/kg/day), NKC cytotoxicity was significantly increased, enhancing the 

immune response to antigenic stimulation, although the delayed-type hypersensitivity (DTH) and 

prostaglandin E2 synthesis were significantly reduced. Selenium administration did not affect the ability 

of resident peritoneal cells to produce interleukin IL-1. Given the enhanced NKC activity at 0.07 and 

0.28 mg selenium/kg/day, but not at 0.7 mg selenium/kg/day, and given the reduced antibody and 

prostaglandin synthesis at 0.7 mg selenium/kg/day, the dose of 0.7 mg selenium/kg/day is identified as 
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3. HEALTH EFFECTS 

the lowest LOAEL. A NOAEL cannot be identified because of the conflict between enhanced NKC 

activity and reduced DTH and prostaglandin E2 synthesis occurring at the same dose levels in this study. 

Antibody responses to ovalbumin were significantly lower in five male antelope (Antilocapra americana) 

fed a diet containing 15 ppm selenium (a mixture of alfalfa and hay naturally high in selenium) for 

164 days than in controls fed a similar diet containing only 0.3 ppm selenium, but there was no difference 

in total globulin concentration between groups (Raisbeck et al. 1996). No clinical signs of selenosis or 

treatment-associated lesions were observed in these animals. 

Treatment of steers with selenomethionine or selenite in food at doses up to 0.808 mg selenium/kg/day 

for 120 days produced symptoms of selenosis (hoof lesions), but did not produce any changes in the 

weight or histology of the spleen or thymus or in the histology of the lymph nodes (O’Toole and Raisbeck 

1995). 

Leukocyte function was significantly reduced in pregnant cows supplemented with 0.135 mg/kg/day 

selenium for 3 months from diets that contained 0.25 (control), 6, or 12 ppm selenium as sodium selenite. 

Treated animals showed a significant decrease in forced antibody production and a depression in 

mitogenic response compared with controls (0.005 mg selenium/kg/day) (Yaeger et al. 1998). No clinical 

signs of selenium toxicosis were observed in any of the cows during the experiment. 

As selenium can enhance some immune system functions, selenium may have a normal physiological 

function in the immune system. This is supported by an 8-week study in which treatment of mice with 

selenium as sodium selenite (0.33 mg selenium/kg/day, dietary) resulted in enhanced ability of cytotoxic 

T-lymphocytes to destroy tumor cells (Kiremidjian-Schumacher et al. 1992). 

Selenium appeared to play a protective role against viral infection in rats (Beck et al. 1995). When 

selenium-deficient rats were inoculated with a benign strain of Coxsackie’s virus (CVB3/0), six separate 

point mutations were identified with the progression of virulence, causing myocarditis. Cocksackie’s 

virus appears to act as a cofactor in the development of the myocardits; this was shown when the virus 

was isolated from blood and tissue of people with Keshan disease (a cardiomyopathy particularly 

prevalent in selenium-deficient growing children and women of child-bearing age). 

No studies were located concerning immunological or lymphoreticular effects in humans or experimental 

animals following oral exposure to selenium sulfide or selenium disulfide. 
SELENIUM 106 

3. HEALTH EFFECTS 

The highest NOAEL values and all LOAEL values from each reliable study for immunological effects 

following oral exposure to selenium or selenium compounds for each species and duration category are 

recorded in Table 3-2 and plotted in Figure 3-2. 

3.2.2.4 Neurological Effects 

Following acute oral exposure to selenium compounds in humans, aches and pains and irritability (Civil 

and McDonald 1978), as well as chills and tremors (Sioris et al. 1980) have been reported. The dizziness 

associated with selenium inhalation exposure has not been documented after selenium ingestion. 

In a 1964 study, Rosenfeld and Beath reported listlessness, a general lack of mental alertness, and other 

symptoms of selenosis in a family exposed for approximately 3 months to well water containing 9 mg 

selenium/L (0.26 mg selenium/kg/day from drinking water). All of the symptoms resolved after use of 

the seleniferous water was discontinued. Because Rosenfeld and Beath (1964) did not estimate the 

family's exposure to dietary selenium, it is not possible to identify the total daily selenium dose associated 

with the symptoms of selenosis in this family. 

In a dietary study of 11 men in a metabolic unit, selenium intake (80 μg/day for the first 21 days, then 

either 13 [n=6] or 356 [n=5] μg/day for 14 weeks) was reported to have no significant effect on mood, as 

measured using the Bi-Polar form of the profile of mood states (POMS) (Hawkes and Hornbostel 1996). 

However, subjects with initially low selenium levels did show significantly greater decreases in mood 

scores during selenium depletion. 

In areas of the People's Republic of China where populations suffer from chronic selenosis, peripheral 

anesthesia and pain in the limbs were reported (Yang et al. 1983). In extreme cases, exaggerated tendon 

reflexes, convulsions, and some paralysis and hemiplegia occurred (Yang et al. 1983). These latter cases 

were associated with an estimated daily dietary intake of selenium of at least 3.22 mg selenium/person/ 

day, averaging 4.99 mg selenium/person/day (Yang et al. 1983). Assuming a weight of 55 kg for Chinese 

men (Yang 1989b), these dietary levels represent 0.027 mg selenium/kg/day and 0.09 mg 

selenium/kg/day, respectively. In another high selenium area, no neurological effects were observed in 

individuals who consumed up to 1.51 mg selenium/day (0.027 mg/kg/day) (Yang et al. 1983). Danish 

geriatric patients with a mean age of 75.3 years were given daily either a placebo or an antioxidant 

cocktail containing 0.004 mg/kg/day of selenium as L-selenomethionine along with zinc, vitamins C, A, 
SELENIUM 107 

3. HEALTH EFFECTS 

B6, and E, and gamma-linolenic acid. After 1 year, whole blood selenium concentrations increased in the 

treated group, and slight but significant improvements in psychological scores were observed (Clausen et 

al. 1989). Because a mixture of nutrients was administered, the improvement in the patients cannot be 

attributed to selenium. People living on ranches with high selenium soils where selenium toxicity in 

livestock had historically been observed were compared to randomly selected residents in Wyoming and 

South Dakota. Daily selenium intake was measured by analysis of duplicate food portions. Subjects 

received a complete physical exam with a symptom questionnaire and laboratory tests. There were no 

biologically significant changes in clinical signs or blood chemistry. Calculated doses ranged from 

0.001 to 0.01 mg selenium/kg/day in the diet (Longnecker et al. 1991). 

An increased incidence (4 observed cases, 0.97 expected, standardized incidence ratio=4.14, 95% 

confidence interval [CI]=1.13–10.60) of amyotrophic lateral sclerosis, a human motor neuron disease of 

unknown origin, was reported for a cohort of 5,182 residents of Reggio Emilia, Italy who had been 

exposed to drinking water containing increased selenium (7–9 μg/L)from 1972 to 1988, compared with 

the incidence among residents of the surrounding area who had received municipal water containing 

<1 μg/L selenium (Vinceti et al. 1996). A subcohort of 2,065 of these individuals who had been exposed 

from 1974 (the earliest date for which a chemical analysis of the municipal tap water was available) was 

also examined and found to have an increased incidence ratio (4 observed cases, 0.47 expected, 

standardized incidence ratio=8.59, 95% CI=2.34–21.98). However, the study is limited by a water level 

of selenium that is not generally considered to be high, a lack of individual measurements of selenium 

exposure, and insufficient information on confounding variables. The lack of data on selenium status 

indicates that the study found a correlation but not causation. 

In a 30-day study of the administration of L-selenomethionine to long-tailed macaques, severe 

hypothermia was observed in two of five animals administered 0.12 mg selenium/kg/day, but not in any 

of the eight animals receiving 0.08 mg selenium/kg/day (Cukierski et al. 1989). However, the increased 

incidence of hypothermia was not statistically significant. Following 1 week of treatment, all animals 

administered L-selenomethionine, including the two macaques treated with 0.01 mg selenium/kg/day, 

exhibited increased drowsiness and lethargy (Cukierski et al. 1989). 

Symmetrical focal poliomyelomalacia and other forms of paralysis were seen in swine exposed to 

0.58–2.1 mg selenium/kg/day after both acute and intermediate exposures (Baker et al. 1989; Goehring et 

al. 1984; Harrison et al. 1983; Mihailovic et al. 1992; Panter et al. 1996; Penrith and Robinson 1996; 

Stowe et al. 1992; Wilson et al. 1983, 1988, 1989). This lesion was noted in animals that showed ataxia, 
SELENIUM 108 

3. HEALTH EFFECTS 

inability to stand, and paralysis of the hind limbs. Additionally, bilateral lesions were noted in the ventral 

horns of the cervical and lumbar/sacral intumescences of the spinal cord. Necrosis and cavitation were 

evident in the larger lesions (Harrison et al. 1983). Bilateral lesions were also observed in several nuclei 

of the brain stem and in the reticular formation (Wilson et al. 1983). Wilson et al. (1983) reproduced the 

syndrome in growing pigs by feeding them sodium selenite at 50 mg selenium/kg in the diet for 20– 

40 days. The study authors did not provide sufficient information to calculate doses on a mg selenium/kg 

body weight basis, but assuming that young swine consume approximately 4% of their body weight each 

day, this dose was approximately 2.1 mg/kg/day. 

In a study of weaned 5-week-old pigs, a dose of 1.3 mg selenium/kg/day given as sodium selenite in 

capsules killed all eight pigs within 10 days. Histopathological lesions were found in the brain and spinal 

cord (Wilson et al. 1989). In a study in which pigs were fed 1.25 mg selenium/kg/day in the form of 

A. bisulcatus, D,L-selenomethionine, or selenate, the selenium in A. bisulcatus was the most potent 

neurotoxin, resulting in complete paralysis in four of five pigs after 5 days of treatment, and in the last pig 

after 3 weeks of treatment (Panter et al. 1996). In pigs fed selenate, three of five developed complete 

paralysis, and one pig developed posterior paralysis after 4–21 days of treatment. Although 

D,L-selenomethionine resulted in the greatest incidence of selenosis, it was the least potent neurotoxicant, 

resulting in posterior paralysis in two of five pigs after 9 and 24 days of treatment; the pigs that did not 

develop paralysis were fed D,L-selenomethionine for approximately 31 days. The form of selenium in 

A. bisulcatus is unknown, although Panter et al. (1996) indicate that it is nonprotein. 

It has long been believed that the blind staggers syndrome in livestock results from consumption of plants 

high in selenium (100–10,000 mg selenium/kg plant) (Rosenfeld and Beath 1964). These plants, which 

include A. bisulcatus, are known as selenium-indicator plants. “Blind staggers” is characterized by 

impaired vision, aimless wandering behavior, reduced consumption of food and water, and finally 

paralysis and death (Rosenfeld and Beath 1964; Shamberger 1986). Trembling of the skeletal muscles 

was observed in steers fed sodium selenite mixed in the feed at doses between 0.6 and 1.1 mg 

selenium/kg/day (Maag et al. 1960). At necropsy, two of six steers exhibited neuronal degeneration of 

the cerebral and cerebellar cortices. However, more recent studies in which cattle were treated with 

known amounts of selenium have not replicated these effects, and it is likely that “blind staggers” is not 

solely the result of selenium toxicity, but may also be attributable to other unidentified causes. For 

example, treatment of 20 steers with selenomethionine or selenite in food at doses up to 0.808 mg 

selenium/kg/day for 120 days produced symptoms of selenosis (hoof lesions), but did not produce any 
SELENIUM 109 

3. HEALTH EFFECTS 

neurological signs associated with “blind staggers” or any treatment-related changes in the histology of 

the central nervous system (O’Toole and Raisbeck 1995). 

Neurological effects have also been reported for mice after acute or intermediate exposures to selenium. 

A single oral dose of selenium dioxide dissolved in water given to mice at 1/10th the LD50 (1.7 mg/kg) 

caused moderate reductions in alertness, spontaneous activity, touch response, muscle tone, and 

respiration. Pentobarbital sleeping time was also significantly increased, and there was moderate 

hypothermia (Singh and Junnarkar 1991). Brain tissue from male BALB/c mice administered sodium 

selenite or seleno-L-methionine in drinking water at 0, 1, 3, or 9 ppm selenium (sodium selenite: 0.03, 

0.24, 0.58, or 1.34 mg selenium/kg/day; seleno-L-methionine: 0.03, 0.26, 0.63, or 1.96 mg 

selenium/kg/day) for 14 days was examined for changes in the concentrations of norepinephrine (NE), 

dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), serotonin (5-HT), and 

5-hydroxyindolacetic acid (5-HIAA) (Tsunoda et al. 2000). Treatment with seleno-L-methionine 

produced no significant changes in the concentrations of any of the neurotransmitters or their metabolites. 

DOPAC, DA, and HVA were increased in the striatum of mice receiving 3 or 9 ppm selenium as selenite. 

The increase was significant at both concentrations for DOPAC and at 3 ppm (but not 9 ppm) for HVA, 

but was not significant at either concentration for DA. No changes were observed for levels of NE, 5-HT, 

or 5-HIAA levels in any brain region of mice treated with sodium selenite. 

Exposure of female BALB/c mice to 0.21 mg selenium/kg/day for 6 months from diets containing 

selenium as sodium selenite resulted in significant changes in behavior during open field testing (Boylan 

et al. 1990). Open field testing measures the arousal level of small rodents and can differentiate between 

fear-related behavior and general arousal. Mice receiving excessive selenium had reduced sniffing 

behavior and exhibited greater activity entering more squares, and more interior squares than mice 

receiving normal selenium diets. These behaviors are indicative of a general state of arousal rather than 

fear-motivated activity. 

No studies were located concerning neurological effects in humans or experimental animals following 

oral exposure to selenium sulfide or disulfide. 

The highest NOAEL values and all LOAEL values from each reliable study for neurological effects 

following oral exposure to selenium or selenium compounds for each species and duration category are 

recorded in Table 3-2 and plotted in Figure 3-2. 
SELENIUM 110 

3. HEALTH EFFECTS 

3.2.2.5 Reproductive Effects 

No studies were located regarding adverse effects on human reproduction following oral exposure to 

elemental selenium or to selenium compounds. Associations between high seminal plasma selenium and 

impaired sperm count or motility have been inconsistently observed in humans (Bleau et al. 1984; Hansen 

and Deguchi 1996; Roy et al. 1990). A 120-day double blind experimental study found no adverse 

changes in sperm indices or reproductive hormone in men (20–45 years old) who consumed a controlled 

diet of foods naturally high or low in selenium (Hawkes and Turek 2001). Eleven subjects were fed a diet 

that provided 0.0006 mg selenium/kg/day for the first 21 days of the study, followed by diets providing 

0.0002 mg selenium/kg/day (6 subjects) or 0.004 mg selenium/kg/day (5 subjects) for 99 days. Semen 

quality (sperm concentration, semen volume, sperm total number, fraction motile sperm, percent 

progressive sperm, mean forward velocity, and various sperm morphology parameters), reproductive 

hormone levels (serum testosterone, follicle-stimulating hormone, luteinizing hormone, prolactin, 

estradiol, and progesterone), and thyroid hormone levels (serum T3 and TSH) were evaluated during 

weeks 3 (baseline values), 8, and 17 (ending values). 

Selenium levels in blood plasma began to change within 3 days of starting the low- and high-selenium 

diets and progressively continued throughout the study (Hawkes and Turek 2001). By week 17, mean 

plasma selenium concentrations had increased by 109% in the high-selenium group and decreased by 

38.5% in the low-selenium group. A similar pattern of changes occurred in seminal plasma selenium, 

although selenium levels in sperm did not change significantly in either group. Mean sperm motility was 

significantly different in the low-selenium subjects and high-selenium groups at week 13, but not at 

weeks 8 or 17. The fraction of motile sperm increased an average of 10% in the low-selenium group by 

week 13, and was essentially the same as the baseline value at week 17. Sperm motility decreased an 

average of 32% in the high-selenium group at week 13, and ended 17% lower than baseline value at 

week 17. ANOVA showed a significant main effect of dietary selenium on sperm motility, as well as a 

significant selenium x time interaction, indicating that the group responses diverged over time. Baseline 

and ending motile sperm fractions in the high-selenium group were 0.588±0.161 and 0.488±0.193, 

respectively; ≥50% motility is considered normal (FDA 1993). The decrease in sperm motility in the 

high-selenium group cannot be clearly attributed to selenium because the effect was not consistent over 

the duration of exposure, is unlikely to be adverse because it is at the low end of the normal range, and is 

not accompanied by any significant changes in other indices of sperm movement (progression or forward 

velocity), or sperm numbers or morphology. Additionally, there were no effects of selenium on serum 
SELENIUM 111 

3. HEALTH EFFECTS 

levels of reproductive hormones, and changes in thyroid hormones, which could affect sperm function, 

were not outside normal ranges (see Endocrine Effects in Section 3.2.2.2). 

A nonsignificant increase in spontaneous abortions (relative risk [RR]=1.73; 95% CI=0.62–4.80) was 

reported among births in the municipality of Reggio Emilia, Italy, where women had been exposed to 

drinking water containing 7–9 ug/L levels of selenium (as selenate, reported estimated intake 10– 

20 ug/day) between 1972 and 1988 (Vinceti et al. 2000a). This study is limited by a level of selenium in 

water that is not considered high, lack of data on selenium status, and insufficient information on 

confounding variables. Selenium deficiency has been implicated as a risk factor for recurrent miscarriage 

in humans (Al-Kunani et al. 2001; Barrington et al. 1996, 1997; Güvenc et al. 2002; Kumar et al. 2002). 

Data from animal studies suggest that exposure to excessive selenium has adverse effects on testosterone 

levels and sperm production and increases the percentage of abnormal sperm (El-Zarkouny et al. 1999; 

Kaur and Parshad 1994; NTP 1994). A significant reduction (49%) in serum testosterone levels was 

reported for New Zealand white rabbits gavaged with 0.001 mg selenium/kg/day as sodium selenite once 

a week for 6 weeks (El-Zarkouny et al. 1999). The percentage of spermatozoa without an acrosome was 

also increased in treated rabbits compared with controls, but the difference was not significant. Sperm 

motility, ejaculate volume, sperm concentration, and total sperm output were all reduced by selenium 

treatment, but statistical analysis of these data was not presented. 

Exposure of Wistar rats to 0.234 mg selenium/kg/day as sodium selenite in water produced testicular 

hypertrophy (Turan et al. 1999a). A dose-related increase in abnormal sperm and a decrease in live sperm 

were observed in wild-caught rats exposed to selenite in the diet at 0.1 and 0.2 mg selenium/kg/day (Kaur 

and Parshad 1994). The percentage of abnormal sperm was 3.9% at 0.1 mg/kg/day and 24.6% at 

0.2 mg/kg/day. The abnormalities observed were principally in the midpiece region of the sperm, the 

region that contains a selenoprotein (Sunde 1990). Decreased sperm counts were observed in rats 

provided with selenate or selenite in drinking water for 13 weeks at a dose of 0.29 mg selenium/kg/day 

for selenate and a dose of 0.17 mg selenium/kg/day for selenite (NTP 1994). Effects on sperm were not 

observed in mice treated with selenate or selenite in the drinking water at doses up to 5.45 mg 

selenium/kg/day for selenate or up to 3.31 mg selenium/kg/day for selenite (NTP 1994). The 

administration of 1.05 mg selenium/kg/day as potassium selenate to rats in drinking water for 1 year did 

not affect male fertility (Rosenfeld and Beath 1954), and the administration of 0.57 mg selenium/kg/day 

as sodium selenate for three generations did not reduce male fertility in mice (Schroeder and Mitchener 

1971b). A short-term reproductive study of the effects of sodium selenate in drinking water on rats at 
SELENIUM 112 

3. HEALTH EFFECTS 

doses (0.418 mg selenium/kg/day) that produced signs of systemic toxicity did not cause any increase in 

sperm abnormalities or lesions of the testis or epididymis (NTP 1996). Selenium administered in the diet 

or in drinking water over short exposure periods (e.g., 1 month) does not appear to affect the fertility of 

female animals unless the intake is sufficiently high to cause general toxicity (Nobunaga et al. 1979). 

Despite a small increase in the number of abnormal length estrous cycles, Nobunaga et al. (1979) found 

no adverse effect on the fertility of female mice from administration of sodium selenite at doses of 

0.34 mg selenium/kg/day in drinking water for 30 days before mating and for 18 days during pregnancy. 

On the other hand, chronic exposure of mice and rats to otherwise nontoxic doses has been shown to 

reduce fertility and to reduce markedly the viability of the offspring of pairs that are able to conceive 

(Schroeder and Mitchener 1971b; Wahlstrom and Olson 1959b). 

A study of supplementation of female pigs with 0.1 or 0.3 ppm selenium (doses not available) 

administered as a selenium-enriched yeast or sodium selenite in the diet, from 60 days before breeding 

until weaning found no adverse effects on reproductive performance (measured by number of offspring) 

or growth (Mahan and Kim 1996). In another study of the effect of selenium on fertility in pigs, females 

fed sodium selenite at 0.4 mg selenium/kg/day from 8 weeks of age exhibited reduced rates of conception 

and also produced offspring with significantly reduced birth weight and weaning weights in the first and 

second litters (Wahlstrom and Olson 1959b). An altered menstrual cycle was reported in monkeys 

administered 0.08 mg selenium/kg/day as L-selenomethionine for 30 days (Cukierski et al. 1989). 

Vaginal cytology of female rats provided with drinking water containing selenate or selenite indicated 

that the rats spent more time in diestrus and less time in proestrus and estrus than the controls (NTP 

1994). This effect occurred following treatment with 0.31 mg selenium/kg/day as selenate or 0.86 mg 

selenium/kg/day as selenite. The animals in these studies were not mated, so it is not known if the effects 

on the estrous cycle had any effect on fertility. Effects on the estrous cycle were not observed in mice 

treated with selenate or selenite in the drinking water at doses up to 7.17 mg selenium/kg/day for selenate, 

or at doses up to 3.83 selenium/kg/day for selenite (NTP 1994). 

In a three-generation reproduction study, selenium administered as sodium selenate (0.57 mg 

selenium/kg/day) in the drinking water of breeding mice produced adverse effects on reproduction 

(Schroeder and Mitchener 1971b). The most notable observed effects included the failure of about half of 

the F3 generation pairs to breed successfully. In a two-generation study using rats, selenium administered 

as potassium selenate had no effect on reproduction at a dose of 0.21 mg selenium/kg/day for 1 year; 

however, decreased fertility and pup survival were noted at 1.05 mg selenium/kg/day (Rosenfeld and 
SELENIUM 113 

3. HEALTH EFFECTS 

Beath 1954). At 0.35 mg selenium/kg/day for 1 year, the number of young successfully reared by the 

females was reduced by 50%, and the body weight of the females was approximately 20% less than that 

of the control females (Rosenfeld and Beath 1954). 

A short-term reproductive study of the effects of sodium selenate in drinking water on rats reported some 

female reproductive toxicity (reduced corpora lutea, reduced implants per litter, shorter estrous cycle), but 

only at doses (0.418 mg selenium/kg/day) that produced signs of severe maternal toxicity, including a 

large reduction in water consumption (NTP 1996). 

In a review of selenium poisoning in domestic animals, Harr and Muth (1972) noted a decreased 

conception rate and an increased fetal resorption rate in cattle, sheep, and horses fed diets naturally 

containing organic selenium compounds at 25–50 mg selenium/kg diet. Assuming that large animals 

consume an amount of food equal to about 2–3% of their body weight daily, the doses would have been 

approximately 0.5–1.5 mg selenium/kg/day. These levels of selenium also produced other signs of 

toxicity, including hair loss, lameness, and degeneration and fibrosis of the heart, liver, and kidneys. In a 

case control study of 136 Holstein cows from four herds, an association of cystic ovaries with blood 

selenium concentrations >108 ng/mL was found (Mohammed et al. 1991). The concentration of 

progesterone in the milk was significantly higher in the controls than in the cows receiving selenium 

supplementation, but no information on the selenium dose was presented. No change in estrus cycle 

length, estrus behavior, progesterone, or estrogen profiles or pregnancy rate was observed in a study of 

the reproductive response of ewes fed alfalfa pellets containing sodium selenate (24 ppm selenium) or 

A. bisculcatus (29 ppm selenium) as a selenium source for 88 days, from >52 days before pregnancy up to 

day 28 of gestation (Panter et al. 1995). Doses could not be calculated as food consumption was not 

listed, and the paper states that the food supply was limited to match that of the group with the lowest 

intake. 

The highest NOAEL value for reproductive effects following intermediate oral exposure to sodium 

selenite and all reliable LOAEL values for reproductive effects following intermediate or chronic oral 

exposure to selenium compounds other than selenium sulfide are recorded in Table 3-2 and plotted in 

Figure 3-2. 
SELENIUM 114 

3. HEALTH EFFECTS 

3.2.2.6 Developmental Effects 

No studies have demonstrated that selenium or its compounds are teratogenic in humans. Robertson 

(1970) reported on the outcome of pregnancies in a laboratory in which workers handled sodium selenite. 

Of the five pregnancies, four ended in spontaneous abortion and one resulted in an infant with bilateral 

clubfoot. The urinary selenium levels in all subjects were similar to those in other individuals living in 

the same area. The limited number of cases, possible exposure to other toxic agents, and other 

confounding factors leave the relationship between sodium selenite and developmental effects 

inconclusive. 

No significant increase in spontaneous abortions (RR=1.73; 95% CI=0.62–4.80) was reported among 

births in the municipality of Reggio Emilia, Italy, where women had been exposed to drinking water 

containing 7–9 μg selenium/L (as selenate) between 1972 and 1988 (Vinceti et al. 2000a). Body weight 

and length at birth were similar in infants of exposed and unexposed women, and no significant increase 

in the prevalence of congenital abnormalities was found for 353 infants of exposed mothers compared 

with the 14,481 births among unexposed women. This study is limited by a level of selenium in water 

that is not considered high, lack of data on selenium status, and insufficient information on confounding 

variables. 

Zierler et al. (1988) performed a case control study of 270 children born in Massachusetts with severe 

congenital heart disease and 665 controls randomly selected from birth certificates. The study compared 

the selenium concentrations in the public drinking water supply used by the mothers close to the time of 

conception to the selenium concentrations in the water consumed by the controls. The results indicated 

that selenium exposure via drinking water was associated with beneficial effects, particularly a reduction 

in the risk of congenital heart defects (cono-truncal defects, venticular septal defects, coarctation of the 

aorta, and patent ductus arteriosis), but many variables are unknown, including other possible 

confounders (no adjustment for age, parity, tobacco, alcohol, drug use, or socioeconomic status), other 

sources of selenium in the mothers' diet and environment, the amount of drinking water consumed, and 

the selenium concentrations in the water during the first trimester. 

Excess selenium is a demonstrated teratogen in birds. However, there is no clear evidence linking 

selenium exposures to teratogenic effects in mammals. Several studies have documented the sensitivity 

of chick embryos to selenium poisoning. Hatchability of eggs is reduced by dietary levels of organic 

selenium in grain that are too low to cause toxicity in other farm animals. The eggs are fertile but often 
SELENIUM 115 

3. HEALTH EFFECTS 

produce grossly deformed embryos lacking eyes and beaks and having deformed wings and feet (Franke 

and Tully 1935; Franke et al. 1936; Gruenwald 1958; Palmer et al. 1973). Deformed embryos have also 

been produced by injection of aqueous sodium selenite or sodium selenate into the air cell of the normal, 

fertile eggs of chickens (Franke et al. 1936; Khan and Gilani 1980). The incidence of malformation 

among coot, duck, stilt, and grebe embryos from eggs of birds ingesting plant and other food from 

irrigation drainwater ponds in the San Joaquin Valley of California was much higher than expected (10– 

42%, depending on the species, versus <1% based on data from other areas) (Ohlendorf et al. 1986a, 

1988). Selenium concentrations in these ponds were >0.3 mg/L. 

The consumption of naturally high seleniferous diets by sheep (Rosenfeld and Beath 1964) and cattle 

(Dinkel et al. 1963) may interfere with normal fetal development and produce malformations. 

Malformations were associated with alkali disease and occurred at dietary levels that produced other toxic 

manifestations, but it is not clear if these reports took into account consumption of other toxic range 

plants. The specific selenium compound or compounds possibly associated with livestock developmental 

toxicity have not been identified. No change in the outcome of pregnancy was observed in a study of the 

reproductive response of ewes fed alfalfa pellets containing sodium selenate (24 ppm selenium) or 

A. bisculcatus (29 ppm selenium) as a selenium source for 88 days, from >52 days before pregnancy up to 

day 28 of gestation (Panter et al. 1995). All lambs appeared normal, and there was no significant 

difference in the number or weight of lambs born to treated and control ewes. Doses could not be 

calculated, as food consumption was not listed, and the paper states that the food supply was limited to 

match that of the group with the lowest intake. 

In an intermediate-duration study, an increased number of deaths between birth and weaning, reduced 

birth weight, and reduced body weight at weaning were observed in offspring of pigs fed selenite at 

0.4 mg/kg/day for an unstated period of time (Wahlstrom and Olson 1959b). Treatment of 15 pregnant 

cows with diets containing 0.25 (control), 6, or 12 ppm selenium (0.005, 0.135, or 0.265 mg Se/kg/day) as 

sodium selenite beginning at 80–110 days gestation and continuing for 3 months resulted in no 

abnormalities among the offspring apart from one calf in the 12 ppm group that was born weak and 

subsequently died (Yaeger et al. 1998). This calf had myocardial lesions similar to those described for 

selenium toxicosis and had markedly elevated hepatic selenium levels, although selenium levels in blood 

and hair of this calf and its dam were lower than average for the 12 ppm group. 

In studies of laboratory mammals, the administration of inorganic selenium compounds at levels that are 

not maternally toxic has not produced terata (Bergman et al. 1990; Chiachun et al. 1991; Ferm et al. 1990; 
SELENIUM 116 

3. HEALTH EFFECTS 

NTP 1996; Poulsen et al. 1989; Rosenfeld and Beath 1954; Schroeder and Mitchener 1971b; ThorlaciusUssing 1990). Ferm et al. (1990) administered a single dose of sodium selenate, sodium selenite, or 

L-selenomethionine (0, 1.8, 2.2, 2.7, 4.0, 5.0, or 5.9 mg selenium/kg/day) to pregnant Syrian hamsters on 

gestation day 8. Pathological examination of the fetuses on day 13 showed that the percentage of 

abnormal litters was significantly increased at doses of ≥2.7 mg/kg. Encephalocele was the major 

malformation noted, and incidences were as follows: 0/71 controls; 4/55 (7.3%) at 1.8 mg/kg; 1/49 (2%) 

at 2.2 mg/kg; 7/66 (10.6%) at 2.7 mg/kg; 15/70 (21.4%) at 4 mg/kg; 9/38 (23.7%) at 5 mg/kg; and 

6/16 (37.5%) at 5.9 mg/kg. Nobunaga et al. (1979) found that administration of sodium selenite in 

drinking water at 0.34 mg selenium/kg/day for 30 days before mating and for 18 days during pregnancy 

slightly, but significantly, reduced fetal growth in mice. However, there was no effect on fetal growth in 

the same study at a dose of 0.17 mg selenium/kg/day. A short-term developmental study (from gestation 

day 6 until birth) of the effects of sodium selenate in drinking water on rats produced some developmental 

toxicity (decreased number of live births, reduced pup weight, increased gestation period), but only at 

doses (0.418 mg selenium/kg/day) that produced signs of severe maternal toxicity including a large 

reduction in water consumption (NTP 1996). Selenium administered as potassium selenate in drinking 

water to male and female rats at a dose of 1.05 mg selenium/kg/day for 1–8 months for two successive 

generations did not cause congenital malformations (Rosenfeld and Beath 1954). Similarly, 

administration of 0.57 mg selenium/kg/day as sodium selenate in the drinking water of breeding mice for 

three generations did not have teratogenic effects, although there was an increased incidence in fetal 

deaths, and a high proportion of the surviving offspring were runts (Schroeder and Mitchener 1971b). 

Poulsen et al. (1989) demonstrated that pigs exposed to 42.4 mg/day of selenium as sodium selenite in 

feed throughout pregnancy produced normal litters, with no adverse effect on piglet survival, litter size, or 

body weight at birth. Body weights of the pigs during pregnancy were not provided, and therefore, 

mg/kg/day doses could not be calculated. Body weight gains of pigs fed selenium as selenite at a dose of 

0.4 mg selenium/kg/day after weaning (duration not specified) were reduced (Wahlstrom and Olson 

1959a). The reduction in body weight gain was greater among pigs from dams not fed selenium during 

gestation and lactation compared to pigs fed selenium (0.4 mg/kg/day) during gestation and lactation. 

Without providing data, the study authors indicated that there was a greater loss of pigs at birth and 

during lactation from sows fed selenium, which may have eliminated susceptible pigs. 

In a teratology study of long-tailed macaques, no gross abnormalities or growth retardations were 

observed in fetuses from mothers administered L-selenomethionine at levels of 0.003, 0.025, 0.15, or 
SELENIUM 117 

3. HEALTH EFFECTS 

0.30 mg selenium/kg/day on gestational days 20–50 (10 animals per group); the mid and high doses were 

maternally toxic (Tarantal et al. 1991). 

The highest NOAEL value and all reliable LOAEL values for developmental effects following 

intermediate or chronic oral exposure to selenium compounds are recorded in Table 3-2 and plotted in 

Figure 3-2. 

3.2.2.7 Cancer 

Early studies reporting that selenium was carcinogenic in mammals after being provided as seleniferous 

corn or wheat in the diet (Nelson et al. 1943), as sodium selenite or sodium selenate in drinking water 

(Schroeder and Mitchener 1971a), or as sodium selenate in the diet (Volgarev and Tscherkes 1967) were 

flawed. The majority of subsequent studies of humans and animals have revealed no association between 

selenium intake and the incidence of cancer (Azin et al. 1998; Beems 1986; Coates et al. 1988; Harr et al. 

1967; Ma et al. 1995; Menkes et al. 1986; Ratnasinghe et al. 2000; Thompson and Becci 1979; Vinceti et 

al. 1995; Virtamo et al. 1987) or a clear chemopreventive association (Birt et al. 1982; Clark et al. 1996a, 

1999; Finley et al. 2000; Ip 1981, 1983; Ganther and Lawrence 1997; Ip and Lisk 1995; Ip et al. 1996, 

1997, 1998, 2000a, 2000b; Jiang et al. 1999; Ma et al. 1995; Medina and Shepherd 1981; Moyad 2002; 

Overvad et al. 1985; Schrauzer et al. 1976, 1977; Shamberger et al. 1976; Soullier et al. 1981; Thompson 

and Becci 1980; Woutersen et al. 1999; Yoshizawa et al. 1998). Some epidemiological and experimental 

evidence suggests that selenium exposure, under certain conditions, may contribute to a reduction in 

cancer risk (Clark et al. 1996a, 1999; El-Bayoumy 2001; Ganther 1999; Moyad 2002; Spallholz 2001; 

Yoshizawa et al. 1998), and the chemopreventive potential of supplemental selenium is currently under 

research (Clark et al. 1999; Duffield-Lillico et al. 2002; Reid et al. 2002). 

The only selenium compound that has been shown to be carcinogenic in animals is selenium sulfide (NTP 

1980c), although there is also some evidence for carcinogenicity due to ethyl selenac (selenium 

diethyldithiocarbamate) (Innes et al. 1969; NCI 1968). These compounds are very different chemically 

from the organic and inorganic forms found in foods and the environment. Human dietary studies 

generally do not identify the selenium form specifically; both organic (from grains and other plant and 

animal products) and inorganic (from drinking water) forms are ingested. Animal bioassays in which 

selenium was administered as sodium selenate, sodium selenite, or organic forms of selenium have all 

shown similar negative results. 
SELENIUM 118 

3. HEALTH EFFECTS 

Excess incidence of melanoma was reported for a cohort of 2,065 individuals that were exposed to 

7–9 μg/L levels of selenium as selenate in the municipal water supply in Reggio Emilia, Italy from 1972 

until 1988 (Vinceti et al. 1998). Eight individuals among the exposed cohort developed melanoma 

compared with 128 in the remainder of the municipal population (total number of individuals not given). 

The standardized mortality ratios (SMRs) were 5.0 (95% CI=1.6–12.0) for males and 3.2 (95% 

CI=1.0–7.7) for females. The authors estimate the general dietary intake of selenium in the area to be 

45–50 μg/day and the excess selenium supplied in the contaminated tap water to be 10–20 μg/day. 

However, the study is limited by the fact that no individual measurements of selenium exposure were 

made, and individuals were classed as exposed or unexposed depending on their place of residence. The 

lack of data on selenium status indicates that the study found a correlation but not causation. Other 

limitations include a water level of selenium that is not generally considered to be high and insufficient 

information on confounding variables. 

A study of the effects of nutritional supplementation with selenium found a significant reduction in 

overall cancer mortality and in the incidence of lung (RR=0.54, 95% CI=0.3–0.98, p=0.04), colorectal 

(RR=0.42, 95% CI=0.18–0.95, p=0.03), and prostate (RR=0.37, 95% CI=0.18–0.71, p=0.003) cancer 

(Clark et al. 1996a, 1999). The original intent of the study was to assess the effects of selenium 

supplementation on nonmelanoma skin cancer. Patients with a history of skin carcinoma 

(1,312 individuals) were randomized into two groups; one group received a selenium supplement of 

200 μg/day, and the other received a placebo. Groups were treated for an average of 4.5 years and 

followed for an average of 6.5 years. Supplementation produced no difference in skin cancer incidence; 

however, secondary end point analyses of the data found a protective effect for selenium for the cancers 

described above. A reanalysis of the lung cancer data added eight cases to the selenium-treated group, 

four cases to the placebo group, and increased follow-up to 7 years (Duffield-Lillico et al. 2002; Reid et 

al. 2002). Selenium supplementation did not reduce lung cancer incidence in the full population 

(RR=0.70, 95% CI=0.40–1.21, p=0.18; hazard ratio [HR]=0.74, 95% CI=0.44–1.24, p=0.26), although a 

nominally significant decrease was observed among subjects with baseline plasma selenium 

concentrations in the lowest tertile (HR=0.42, 95% CI=0.18–0.96, p=0.04). The analysis for the middle 

and highest tertiles of baseline selenium level showed HRs of 0.91 and 1.25, suggesting that there was a 

trend toward a reduction in risk of lung cancer with selenium supplementation. 

Supporting evidence for an antiprostate cancer effect of selenium was obtained for a nested case-control 

design within the Health Professional Follow-up study (Yoshizawa et al. 1998), which found that higher 
SELENIUM 119 

3. HEALTH EFFECTS 

prediagnostic selenium levels were associated with reduced prostate cancer incidence. This study 

included 33,737 male health professionals aged 40–75 years who provided toenail clippings in 1987. The 

cohort was assessed by questionnaire for incidence of new cases of prostate cancer from 1989 to 1994. 

Higher levels of selenium in toenail clippings were significantly associated with a reduced risk of prostate 

cancer. After controlling for factors such as a family history of prostate cancer, body mass index, calcium 

intake, lycopene intake, saturated fat intake, vasectomy, and geographical region, the odds ratio (OR) was 

0.35 (95% CI=0.16–0.78, p for trend=0.03). Studies of selenium supplementation have generally shown a 

reduction in prostate cancer risk only in individuals who had lower levels of baseline plasma selenium, 

whereas subjects with normal or higher levels did not benefit and may have an increased risk for prostate 

cancer (Moyad 2002). 

Epidemiological studies that focused on the selenium concentration of forage crops as an indicator of 

available dietary selenium indicated an inverse association between selenium levels and cancer 

occurrence, with few exceptions. In the United States, male mortality due to cancer of the tongue, 

esophagus, stomach, intestine, rectum, liver, pancreas, larynx, lungs, kidneys, and bladder was 

significantly lower in states with high selenium levels in forage crops (concentrations in excess of 

0.10 mg selenium/kg) (Shamberger et al. 1976). For females in states with high selenium levels, 

significantly lower cancer death rates were found for cancer of the esophagus, stomach, intestine, rectum, 

liver, pancreas, lungs, bladder, thyroid, breast, and uterus (Shamberger et al. 1976). Only male and 

female mortality due to cancer of the skin and eye, male mortality due to cancer of the lip and aleukemic 

leukemia (a deficiency or absence of leukocytes in the blood due to leukemia), and female mortality due 

to dermal melanoma were associated with high selenium levels in forage crops. Many of the high 

selenium areas are in the southwestern portion of the United States, and therefore, exposures to ultraviolet 

light may have contributed to the skin cancers observed in these areas (Shamberger et al. 1976). In a 

comparison of selenium intake and cancer mortality rates in different countries, Schrauzer et al. (1977) 

detected a cancer chemopreventive association between the selenium content of the diet and age-corrected 

cancer mortality from leukemia and cancers of the intestine, rectum, breast, ovary, prostate, lung, 

pancreas, skin, and bladder. 

In a case control study of lung cancer patients, Menkes et al. (1986) found that the risk of lung cancer was 

not associated with serum selenium levels (0.113 and 0.110 mg selenium/L in cases and controls, 

respectively), but was significantly increased with decreasing serum levels of vitamins A and E. The 

study authors suggested that high serum selenium levels were significantly associated with an increased 

incidence of squamous cell carcinoma as compared to other cellular tumor types, but the statistical 
SELENIUM 120 

3. HEALTH EFFECTS 

analysis used was flawed. In a region of China with high rates of stomach cancer and low intake of 

several micronutrients (selenium not specifically stated), an intervention trial in 29,584 adults for 

5.25 years demonstrated a 21% decrease in stomach cancer in the randomly selected group receiving a 

nutritional supplement of beta carotene (15 mg/day), vitamin E (30 mg/day), and selenium (50 μg 

selenium/day as selenium yeast) (Blot et al. 1993). However, because the three nutrients were given in 

combination to a nutritionally deficient population, it is not possible to determine what part of this effect 

(if any) was due to selenium. 

Low serum selenium levels have been associated with an increased incidence of cancer in some 

prospective epidemiological studies (Salonen et al. 1984, 1985; Willet et al. 1983). In the United States, 

Willet et al. (1983) found that the risk of cancer for subjects in the lowest quintile (fifth) of serum 

selenium concentrations (<0.115 mg selenium/L) was twice that of subjects in the highest quintile 

(>0.154 mg selenium/L). In Finland, Salonen et al. (1985) found the risk of fatal cancer for subjects in 

the lowest tertile (third) of serum selenium concentrations (<0.047 mg selenium/L) was 5.8 times higher 

than that of the remaining subjects. Mean serum selenium levels in Americans (0.129 mg selenium/L 

cases; 0.136 mg selenium/L controls) (Willett et al. 1983) are more than twice the mean serum selenium 

levels in the Finns (0.0505 mg selenium/L for cases; 0.0543 mg selenium/L for controls) (Salonen et al. 

1984). Although the age-specific risk of fatal cancers in the two populations cannot be calculated from 

the data reported, the overall incidence of cancer in the 4-year Finnish study was less than half that in the 

5-year U.S. study. In addition, other prospective studies of Americans have found no correlation between 

fatal cancer and blood selenium concentrations (Coates et al. 1988). Thus, one may not be able to predict 

relative cancer risks with serum selenium levels in one population based on data from another population. 

A 9-year prospective follow-up study was conducted by Virtamo et al. (1987) on a group of men in 

Finland. At the beginning of the study, blood samples were taken as part of a study of coronary heart 

disease and other atherosclerotic diseases. Cancer data were collected from central registries for the years 

1976 through 1983. The results indicated no association between low serum selenium levels (<0.045 mg 

selenium/L) and an increased risk of cancer. Evidence suggests that combined dietary deficiencies of 

vitamin E and selenium may be associated with increased cancer risk (Salonen et al. 1985). 

Epidemiological studies of breast cancer have found inverse correlations, positive correlations, and no 

correlations between tissue selenium concentrations and cancer incidence (recently reviewed by Garland 

et al. 1993). In a case control study of plasma selenium and breast cancer in which the controls had 

benign breast disease, a preventive effect of selenium was found only among individuals who had higher 
SELENIUM 121 

3. HEALTH EFFECTS 

plasma selenium and were not taking selenium supplementation (Hardell et al. 1993). This effect was 

significant (odds ratio 0.38) at a serum selenium concentration range of 0.08–0.09 mg/L in women 

50 years old or more. GPX activity in erythrocytes was not found to be a marker for the risk of breast 

cancer. A case control study of 162 cases of breast cancer in Dutch women did not find a significant 

difference in dietary, plasma, erythrocyte, or toenail selenium between cases and 529 controls when 

multivariate-adjusted odds ratios were calculated. Dutch women have lower selenium intake than women 

in the United States and one of the highest incidences of breast cancer in Western Europe. The authors of 

this study surmised that other studies reporting an inverse relationship between selenium levels and breast 

cancer may be seeing an effect of the cancer (e.g., decreased uptake of selenium or anorexia), rather than 

lower selenium level contributing to the development of cancer (van't Veer et al. 1990). Similarly, a large 

prospective study of 434 cases in the United States found no correlation between selenium content in 

nails, established as a long-term marker of selenium (Hunter et al. 1990a), and breast cancer (Hunter et al. 

1990b). It is interesting to note that a more recent investigation of the same cancer cases found an inverse 

correlation between vitamin A (retinoids) in the diet and breast cancer (Hunter et al. 1993). Retinoids are 

believed to have chemopreventive activity (Clausen et al. 1989; Hunter et al. 1993). Although the data as 

a whole for breast cancer and tissue selenium concentrations do not support a clear chemopreventive 

effect for selenium, it is possible that very high selenium concentrations or very low selenium 

concentrations outside the ranges observed in these studies could play a role in human cancer risk 

(Garland et al. 1993). 

There were several inadequacies in the early studies that reported carcinogenic effects in animals 

following oral administration of selenium-containing compounds. Nelson et al. (1943) (also reported as 

Fitzhugh et al. 1944) administered naturally seleniferous corn or wheat diets containing 5, 7, or 10 mg 

selenium/kg diet (0.25, 0.35, or 0.50 mg selenium/kg/day) to female rats for 2 years. Selenium 

administration produced high mortality (69%) in all treatment groups by the end of the first 12 months, 

and the first tumors appeared after 18 months of treatment. Tumors developed only in animals with 

cirrhotic livers, and the tumors were reported to be nonmalignant. The possible contribution of overt 

hepatotoxicity to the development of liver tumors is not known. The incidences of tumors in the 

surviving animals in the three dose groups were 6/25, 3/21, and 2/7, respectively. The investigators had 

difficulty discerning malignant from nonmalignant tumors, and most animals had died of cirrhosis of the 

liver before the appearance of liver tumors. These difficulties cast doubt on the conclusion of the 

investigators that selenium induced tumor formation in these rats. 
SELENIUM 122 

3. HEALTH EFFECTS 

A statistically significant increase was reported in the incidence of all tumors and malignant tumors in rats 

administered 0.28–0.42 mg selenium/kg/day as sodium selenite or sodium selenate in drinking water for a 

lifetime (Schroeder and Mitchener 1971a). Not all autopsied animals were examined histologically, 

however, and high mortality in all groups occurred as a result of a virulent pneumonia epidemic that 

occurred during the study. In addition, the statistical analysis failed to account for the fact that the 

selenium-treated rats lived longer than did the control rats. Analysis of the incidence of tumors among 

animals with equal longevities indicates that the incidence of tumors in the selenate-treated rats was not 

significantly different from that in the controls. 

A series of dietary studies assessed the effects of various dietary supplements on selenium tumor 

induction in male rats (Volgarev and Tscherkes 1967), but the conclusions that can be drawn from these 

experiments are limited since they did not include controls. Tumors (primarily liver) were found in 

10/23 male rats administered sodium selenate in the diet at a dose of 0.34 mg selenium/kg/day for more 

than 18 months (Volgarev and Tscherkes 1967). The first tumors appeared after 18 months of selenium 

administration, by which time, 43% of the animals had already died (group started with 40 animals). 

Tumors were also found in 3/16 male rats administered sodium selenate in the diet at an initial dose of 

0.34 mg selenium/kg/day for 6 months, followed by 0.68 mg/kg/day until the animals’ death (Volgarev 

and Tscherkes 1967). In a third group of experiments, no tumors were found in 200 male rats 

administered sodium selenate in the diet (0.34 mg selenium/kg/day) for 26 months. However, there was 

very high mortality among these rats, and survival time was 10 months shorter than among the similarly 

fed animals in the first experiment. The authors noted that an additional 200 male rats were maintained in 

their laboratory during these experiments and fed stock rations. The life spans of these animals exceeded 

those used in the experiments and no tumors were found at autopsy. 

More recent animal bioassays have failed to demonstrate any association between excessive selenium 

exposure and carcinogenesis. Chen et al. (2000) reported a significant increase in rat esophageal 

adenocarcinogenesis in response to supplementation with 0.06 mg selenium/kg/day as sodium selenite for 

40 weeks. However, selenium supplementation has generally been shown to significantly inhibit tumors 

induced by chemicals, viruses, or ultraviolet light (Birt et al. 1982; Finley et al. 2000; Ip 1981, 1983; Ip 

and Lisk 1995; Ip et al. 1996, 1997,1998, 2000a, 2000b; Jabobs 1983; Jacobs et al. 1977a, 1977b, 1979, 

1981; Jiang et al. 1999; Medina and Shepherd 1981; Overvad et al. 1985; Schrauzer et al. 1976; Soullier 

et al. 1981; Thompson and Becci 1980; Woutersen et al. 1999). Results following administration of 

selenium as sodium selenate, sodium selenite, and organic forms of selenium are similar. Additional 
SELENIUM 123 

3. HEALTH EFFECTS 

research reviewed in El-Bayoumy (1991, 1995, 1997) indicates that synthetic organoselenium compounds 

may be more potent cancer preventive agents than selenate, selenite, or the selenoamino acids. 

Two sources reported the results of a study of rats administered sodium selenate or sodium selenite in the 

diet for a lifetime (Harr et al. 1967; Tinsley et al. 1967). A vehicle control and two positive control 

groups (administered a known hepatocarcinogen, N-2-fluorenyl-acetamide [FAA]) were included. 

Mortality was high in the highest dose group (0.8 mg selenium/kg/day), and therefore, selenium 

administration was discontinued. Longevity was reduced in animals fed 0.4 mg selenium/kg/day, but not 

in the animals administered lower doses. Of the original 1,437 experimental animals, 1,126 were 

necropsied. Half of the 88 FAA-fed rats developed neoplasms, half of which were hepatic carcinomas, 

indicating that the strain of rat and dietary conditions were compatible with the development of hepatic 

carcinogenesis. The incidence of cancer of all types in the necropsied control rats (11 out of 482, or 

2.3%) was somewhat higher than the incidence of cancer in the selenium-treated animals that were 

necropsied (9 out of 553, or 1.6%). A statistical analysis of the data from this study was not reported. 

Although the reduced longevity of animals administered 0.4 mg selenium/kg/day might have prevented 

the observation of some late-developing cancers, the large number of rats necropsied, the end points 

examined, and the doses administered provide credible evidence of the lack of carcinogenic potential of 

sodium selenate or selenite. 

Mice were fed tortula yeast diets containing up to 1.0 mg selenium/kg diet (equivalent to 0.13 mg 

selenium/kg body weight/day) as sodium selenite for 2 weeks prior to a single application of 0.125 mg 

7,12-dimethylbenz[a]anthracene (DMBA) to the skin or repeated daily applications of 0.25 mL of a 

0.03% solution of benzo[a]pyrene in acetone for 27 weeks (Shamberger 1970). The highest dose of 

selenite used, 0.13 mg selenium/kg/day, significantly decreased the number of tumors induced by both 

aromatic compounds. No significant increase was found in the incidence of spontaneous tumors in mice 

following administration of 3 mg selenium/L in drinking water as either sodium selenite or sodium 

selenate for a lifetime (Schroeder and Mitchener 1972). This level corresponds to doses of 0.31–0.34 mg 

selenium/kg/day for the males and 0.42 mg selenium/kg/day for the females. The single dose 

administered, however, might not have been the maximal dose that could be tolerated. There were 7% 

more malignant tumors in the selenium-treated animals (13 out of 88 sectioned, or 15%) than in the 

controls (10 out of 119 sectioned, or 8%), but the difference was not statistically significant. The forms 

of selenium administered did not influence the incidence of tumors. In this study, only 88 out of 

211 selenium-treated animals and 109 out of 209 control animals were examined histologically. 
SELENIUM 124 

3. HEALTH EFFECTS 

The only selenium compound that has been shown to be carcinogenic in animals is selenium sulfide (NTP 

1980c), although there is some inconclusive evidence that ethyl selenac may also be carcinogenic (Innes 

et al. 1969; NCI 1968). A statistically significant increase in hepatomas (0/16 controls; 12/16 treated) 

was observed in male mice of one strain (C57BL/6 x C3H/Anf)F1) receiving 2 mg selenium/kg as ethyl 

selenac, but not in male or female mice of another strain (C57BL/6 x AKR)F1) receiving the same dose 

(Innes et al. 1969; NCI 1968). 

Statistically significant increases in hepatocellular carcinomas and adenomas in rats and hepatic 

carcinomas and adenomas, as well as alveolar/bronchiolar carcinomas and adenomas, in female mice 

have been observed following chronic oral exposure to selenium sulfide (NTP 1980c). The incidence of 

hepatocellular carcinomas in rats was 1/50, 0/50, and 15/49 in males and 0/50, 0/50, and 21/50 in females 

at 0, 3, and 15 mg selenium sulfide/kg/day, respectively. In mice, the incidences of hepatocellular 

carcinomas and adenomas were 15/50, 14/50, and 23/50 in males, and 0/49, 2/50, and 25/49 in females at 

0, 20, and 100 mg selenium sulfide/kg/day, respectively. Selenium sulfide is a pharmaceutical compound 

used in some antidandruff shampoos and is not administered orally. Because selenium sulfide is not 

absorbed through the skin, use of shampoos containing this compound should be safe, unless one 

intentionally consumes the product or has open cuts or sores on the scalp or hands. Chemically, selenium 

sulfide and ethyl selenac are very different from the organic and inorganic selenium compounds found in 

foods and in the environment. 

In 1975, the International Agency for Research on Cancer (IARC) evaluated the literature relating 

selenium to carcinogenesis in both humans and animals. The Agency stated that the available data 

provided no suggestion that selenium is carcinogenic in humans (IARC 1975a), and IARC subsequently 

assigned selenium to Group 3: not classifiable as to its carcinogenicity to humans (IARC 1987). The 

forms of selenium considered included sodium selenate, sodium selenite, and the organic forms of 

selenium contained in plant materials. Separate evaluations of ethyl selenac and methyl selenac assigned 

them to Group 3, also (IARC 1975a, 1987). According to EPA, selenium is not classifiable as to its 

carcinogenicity in humans and is rated as Group D (IRIS 2003). The evidence for selenium sulfide, 

however, is sufficient to classify it as Group B2 (probable human carcinogen) (IRIS 2003). 
SELENIUM 125 

3. HEALTH EFFECTS 

3.2.3 Dermal Exposure 

3.2.3.1 Death 

No studies were located concerning death in humans after dermal exposure to selenium or selenium 

compounds. In a range-finding study using mice dermally exposed to selenium sulfide for a maximum of 

17 applications, 8 out of 20 animals died at 714 mg selenium sulfide/kg (NTP 1980a). However, the 

effects noted in this study were equivocal since there was no indication that the application sites were 

covered to prevent ingestion. Further, severe skin damage developed, and this may have led to direct 

systemic absorption of the compound. 

3.2.3.2 Systemic Effects 

No studies were located concerning respiratory, cardiovascular, gastrointestinal, hematological, 

musculoskeletal, hepatic, renal, endocrine, or body weight effects in humans or other animals following 

dermal exposure to selenium or selenium compounds. 

Dermal Effects. Skin toxicity in humans, notably skin rashes, burns, and contact dermatitis, has been 

reported for both acute and chronic exposure to selenium fumes and acute exposures to selenium dioxide 

(Middleton 1947). No effects were detected in a study of eight women exposed daily for 2 weeks to an 

experimental sunscreen lotion containing up to 0.003 mg/kg/day selenium as L-selenomethionine (Burke 

et al. 1992a). A case report of a severe allergic skin response following intermediate exposure to sodium 

selenite (Senff et al. 1988) is discussed under immunological effects. Single topical exposures to 

selenious acid resulted in purpura, inflammation around hair follicles, and a pustular rash with some 

ulceration in exposed workers (Pringle 1942). However, these effects may have been due to the caustic 

effects of the acid. A single case report of hyperpigmentation and hair loss after use of a shampoo 

containing 1% selenium sulfide was located (Gillum 1996), but a study of the efficacy of an antidandruff 

shampoo containing 1% selenium sulfide found no adverse effects after 6 weeks of use by 150 individuals 

(Neumann et al. 1996). 

Application of 100 μL of a lotion (oil-in-water emulsion) containing 0.02% selenium as selenomethionine 

3 times a week to the shaved backs of mice for 39 weeks did not result in significant dermal effects (Burk 
SELENIUM 126 

3. HEALTH EFFECTS 

et al. 1992b). Dermal effects were also not observed in hairless mice treated in the same manner for 

49 weeks. 

In mice, topical application of selenium sulfide resulted in erythema and skin irritation at 29 mg/kg, 

acanthosis at 143 mg/kg, and severe skin damage at 714 mg/kg (NTP 1980a). 

Ocular Effects. No studies were located regarding ocular effects in humans after dermal exposure to 

selenium or selenium compounds. However, older reports on eye contact with selenium or selenium 

compounds indicate that acute exposure to selenium dioxide caused ocular and conjunctival irritation, and 

caused severe pain, lacrimation, blurred vision, and dulled corneas upon contact (Middleton 1947). Brief 

exposure to clouds of selenium fumes resulted in lacrimation, irritation, and redness of the eyes (Clinton 

1947). 

No studies were located regarding ocular effects in laboratory animals after dermal exposure to selenium 

or selenium compounds. 

3.2.3.3 Immunological and Lymphoreticular Effects 

A 1988 case report describes a female laboratory technician who developed severely pruritic vesicles 

between the fingers after 6 months of exposure to a medium containing selenium. After 2 years, the 

severity of the symptoms increased to include eczema on the face and neck, watering eyes, and two 

asthma attacks within a 2-month period. Sodium selenite or the medium containing selenium were the 

only positive patch tests (Senff et al. 1988). 

No studies were located regarding immunological and lymphoreticular effects in laboratory animals after 

dermal exposure to selenium or selenium compounds. 

No studies were located regarding the following health effects in humans or laboratory animals after 

dermal exposure to selenium or to selenium compounds: 
SELENIUM 127 

3. HEALTH EFFECTS 

3.2.3.4 Neurological Effects 

3.2.3.5 Reproductive Effects 

3.2.3.6 Developmental Effects 

3.2.3.7 Cancer 

No studies were located regarding carcinogenic effects in humans after dermal exposure to selenium or 

selenium compounds. 

The results of most animal studies have not indicated that elemental selenium or selenium compounds are 

carcinogenic when topically applied to the skin of experimental animals (NTP 1980a, 1980b; Shamberger 

1970). Several studies indicate that selenium compounds may protect against effects of known dermal 

carcinogens (polynuclear aromatic hydrocarbons [PAHs] and ultraviolet light). Shamberger (1970) 

reported that topical application of a solution containing 0.0005% sodium selenide significantly reduced 

the number of dermal papillomas induced by painting DMBA on the shaved backs of mice. More 

recently, Burke et al. (1992b) reported orally and topically administered l-selenomethionine decreased 

ultraviolet burns and skin cancer in albino (BALB:c) and hairless pigmented (Skh:2) female mice. 

Only one study was found in which tumor development was reported after topical administration of 

selenium ointment (Tsuzuki et al. 1960). An unspecified number of mice were exposed to an unspecified 

amount of ointment containing 2.5, 5.0, 7.5, or 10% elemental selenium 6 days/week for an unspecified 

period of time by topical administration to hip skin. Tumors developed on the base of the necks of two 

female mice. Ingestion of the compound was possible because the animals may have licked the ointment. 

No other details were reported. The study is inconclusive because of the lack of controls, short duration, 

and inadequate description of the study protocol and results. 

The National Toxicology Program (NTP 1980a) conducted a dermal application study of selenium 

monosulfide. The compound was applied to the skin of groups of 50 male and 50 female Swiss mice at 0, 

0.5, or 1.0 mg selenium sulfide/mouse, 3 days/week for 86 weeks. The application sites were not 

covered; therefore, ingestion of the test compounds was possible. The incidence of tumors in the treated 

groups did not differ significantly from that in the control group. 
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3. HEALTH EFFECTS 

NTP (1980b) also tested Selsun, a prescription dandruff shampoo containing 2.5% selenium sulfide (also 

a mixture of the mono- and disulfides), for carcinogenic properties. Groups of 50 male and 50 female 

Swiss mice were dermally exposed to a 0, 25, or 50% solution of Selsun in distilled water 3 days/week for 

86 weeks. These doses were equivalent to 0, 0.31, or 0.625 mg selenium sulfide/mouse/day. The 

incidences of alveolar or bronchiolar adenomas or carcinomas in male mice were significantly increased 

over vehicle control values, but not over untreated control values. There was no significant effect in 

female mice. Some ingestion of the compound was possible, because the application sites were not 

covered. Also, the male mice may have been susceptible to another ingredient in the shampoo (the 

chemical composition of the shampoo was not reported), or the bioassay may have been too short due to 

decreased survival to detect a carcinogenic effect in females. Male mice that received dermal application 

of slightly larger doses of selenium sulfide (NTP 1980a) did not develop significantly more cancers than 

the controls. 

3.2.4 Other Routes of Exposure 

Endocrine Effects. Intraperitoneal injection of diabetic rats with sodium selenate has been reported 

to have insulin-like effects, producing a decrease in plasma glucose concentrations (McNeill et al. 1991). 

However, it is not clear that this is due to an effect of selenium on insulin metabolism, since food and 

water consumption were also decreased, and this is likely to have produced the decreased glucose levels. 

Neurological Effects. Intraperitoneal injection of selenium (3.0 mg Se/kg as sodium selenite) into 

male Sprague-Dawley rats produced a significant increase (70%) in dopamine overflow from the striatum 

(as measured by an implanted dialysis probe) with a concomitant significant reduction in HVA levels 

(Rasekh et al. 1997). DOPAC levels were not changed. Direct infusion of 10 mM selenium into the 

striatum also produced a significant increase in dopamine overflow accompanied by slight, but significant 

decreases in HVA and DOPAC. Direct infusion of 10 mM selenium into the nucleus accumbens also 

produced a rapid and significant increase in dopamine overflow, but with no changes in DOPAC or HVA 

concentrations. The selenium induced changes in dopamine overflow were suppressed by the dopamine 

receptor agonist quinpirole. 
SELENIUM 129 

3. HEALTH EFFECTS 

3.3 GENOTOXICITY 

Inorganic selenium compounds have been observed to have both genotoxic and antigenotoxic effects. 

The antigenotoxic effects generally occur at lower selenium exposure levels than the frank genotoxicity. 

This discussion will focus on genotoxic effects only. In vitro studies of the genotoxicity of selenium 

compounds are summarized in Table 3-4, and in vivo studies of the genotoxicity of selenium compounds 

are summarized in Table 3-5. 

Selenium dioxide was found to be mutagenic in both the Ames and the VITO-TOX Salmonella 

typhimurium tests of genotoxicity (van der Lelie et al. 1997). 

In general, sodium selenite and sodium selenate have produced mixed results in bacterial mutagenicity 

test systems (Table 3-4). Sodium selenite induced base-pair substitution mutations using S. typhimurium 

and was also positive in the transformation assay using Bacillus subtilis (Kramer and Ames 1988; 

Nakamuro et al. 1976; Noda et al. 1979). However, negative results have also been reported for sodium 

selenite both in S. typhimurium and the rec assay using B. subtilis (Lofroth and Ames 1978; Noda et al. 

1979). Sodium selenate, on the other hand, has tested positive in S. typhimurium (base-pair substitution) 

and in the rec assay using B. subtilis (Lofroth and Ames 1978; Noda et al. 1979), but has tested negative 

using the transformation assay in B. subtilis (Nakamuro et al. 1976). 

Results with mammalian cell systems are also mixed, although sodium selenite is more consistently 

genotoxic in these systems. Sodium selenite has been observed to induce unscheduled deoxyribonucleic 

acid (DNA) synthesis (UDS), chromosomal aberrations, and sister chromatid exchange in cultured human 

fibroblasts (Lo et al. 1978; Ray et al. 1978; Whiting et al. 1980); UDS in Chinese hamster V79 cells 

(Sirianni and Huang 1983); and chromosomal aberrations in cultured Chinese hamster ovary cells 

(Whiting et al. 1980). However, sodium selenate induced chromosomal aberrations in Chinese hamster 

ovary cells (Whiting et al. 1980) and UDS in Chinese hamster V79 cells (Sirianni and Huang 1983), but 

did not induce chromosomal aberrations in human leukocytes or cultured human fibroblasts (Lo et al. 

1978; Nakamuro et al. 1976). A comparison of cytotoxicity and induction of tetraploidy in Chinese 

hamster V79 cells induced by sodium selenite or its major excretory product trimethylselenonium found 

that sodium selenite was about 1,000 times more cytotoxic than trimethylselenonium, but that neither 

compound produced a significant change in mitotic index (Ueda et al. 1997). 
SELENIUM 130 

3. HEALTH EFFECTS 

Table 3-4. Genotoxicity of Selenium In Vitro 

Result 

With Without 

Species (test system) End point activation activation Reference 

Prokaryotic organisms: Mutation

 Salmonella typhimurim (Na2SeO3) – Lofrothand 

(Na2SeO4) NT + Ames 1978

 S. typhimurim (SeO2) NT + van der Lelie 

et al. 1997

 S. typhimurim TA100 (Na2SeO3) NT + Noda et al. 

 S. typhimurium TA98, TA1537 NT – 1979

 S. typhimurium TA100 (Na2SeO4) NT + 

 S. typhimurium TA98, TA1537 NT – 

 Bacillus subtilis rec assay (Na2SeO3) NT – Noda et al. 

1979 

 B. subtilis rec assay (Na2SeO4) NT + Kanematsu et 

(SeO2) NT + al. 1980

 B. subtilis transformation (SeO2) NT + Nakamuro et 

(Na2SeO3) NT + al. 1976 

(Na2SeO4) NT – 

Eukaryotic organisms:

 Mammalian cells Chromosomal aberrations 

Chinese hamster ovary (Na2SeO3) NT + Whiting et al. 

(Na2SeO4) NT + 1980

 Human leukocytes (SeO2) NT + Nakamuro et 

(Na2SeO3) NT + al. 1976

(Na2SeO4) NT – 

 Human lymphocytes (Na2SeO4) NT + Biswas 1997

 Human lymphocytes (Na2SeO3) NT + Biswas et al. 

(Na2SeO4) NT + 2000

 Human lymphocytes (Na2SeO3) NT + Khalil 1989 

(Selenomethionine) NT + 

Cultured human fibroblasts (Na2SeO3) + + Lo et al. 1978 

(Na2SeO4) – – 

Tetraploidy 

Chinese hamster V79 cells (Na2SeO3) NT + Ueda et al. 

(Trimethylselenonium) NT + 1997 

DNA strand breaks 
SELENIUM 

3. HEALTH EFFECTS 

131 

Table 3-4. Genotoxicity of Selenium In Vitro 

Result 

Species (test system) End point 

With 

activation 

Without 

activation Reference 

Mouse mammary carcinoma (Na2SeO3) NT + Lu et al. 

 cells	 (Na2SeO4) NT + 1995b 

(Methylselenocyanate) NT – 

(Se-methylseleno- NT – 

cysteine) 

Unscheduled DNA synthesis 

Cultured human fibroblasts	 (Na2Se) NT + Whiting et al. 

(Na2SeO3) NT + 1980 

(Na2SeO4) NT + 

Sister chromatid exchange 

Cultured human fibroblasts (Na2SeO3) NT + Ray et al. 

1978

 Human lymphocytes (Na2SeO3) NT + Khalil 1989 

(Selenomethionine) NT + 

(Selenocystine) NT + Khalil 1994 

– = negative result; + = positive result; DNA = deoxyribonucleic acid; NT = not tested; (Na2Se) = sodium selenide; 

(Na2SeO3) = sodium selenite; (Na2SeO4) = sodium selenate; (SeO2) = selenium dioxide 
SELENIUM	 132 

3. HEALTH EFFECTS 

Table 3-5. Genotoxicity of Selenium In Vivo 

Species (test system) End point	 Results Reference 

Human lymphocytes Chromosomal aberrations, –	 Norppa et al. 

(Na2SeO3) sister chromatic exchanges 1980a
 

Monkey (Macaca fisciculari) Micronuclei + (adult toxic dose) Choy et al. 1989 

bone marrow (L-seleno- – (fetal at maternally Choy et al. 1993
 

methionine) toxic doses)
 

Mouse bone marrow Chromosome breaks and Biswas et al. 1997
 

(Na2SeO3) spindle disturbances + 

(Na2SeO4) +
 

Mouse bone marrow Chromosome breaks and Biswas et al. 1999a
 

(Na2SeO3) spindle disturbances + 

(Na2SeO4) +
 

Mouse bone marrow Micronucleus induction Itoh and Shimada 

(H2SeO3) + 1996
 

(Na2SeO4) +
 

Mouse bone marrow Micronucleus induction + Rusov et al. 1996
 

(H2SeO3)
 

Rat bone marrow (Na2SeO3) Chromosomal aberrations + Newton and Lilly 

1986 

Rat bone marrow (SeS) Chromosomal aberrations – Moore et al. 1996b 

Rat bone marrow (SeS) Micronucleus induction +	 Moore et al. 1996b 

Rat spleen (SeS) Chromosomal aberrations –	 Moore et al. 1996b 

Rat spleen (SeS) Micronucleus induction –	 Moore et al. 1996b 

Rat lymphocytes (Na2SeO3) Chromosomal aberrations –	 Newton and Lilly 

1986 

+ = positive result; – = negative result 
SELENIUM 133 

3. HEALTH EFFECTS 

The addition of glutathione to test mixtures enhances the genotoxicity of sodium selenite, sodium 

selenate, and sodium selenide in bacterial test systems, indicating that production of a reactive species 

mutagenic for bacteria occurs via a reductive mechanism following concomitant exposure to these 

compounds (Whiting et al. 1980). This finding is supported by results in mammalian test systems. For 

example, in cultured human leukocytes, sodium selenite induces chromosome aberrations and sister 

chromatid exchanges (Nakamuro et al. 1976; Ray and Altenburg 1978; Ray et al. 1978). Sister chromatid 

exchange was not observed at similar sodium selenite concentrations in a human lymphoblastoid cell line; 

however, exchanges were observed when these same cells were incubated with sodium selenite and red 

blood cell lysate (Ray and Altenburg 1978). The observation that internal constituents of red blood cells 

may contribute to the genotoxicity of sodium selenite supports the suggestion that metabolism is involved 

in the production of an active species following exposure to sodium selenite in these test systems. The 

active species responsible for the genotoxic effects is not known. 

At high concentrations, sodium selenite induces unscheduled DNA synthesis and chromosome 

aberrations in cultured human fibroblasts (Lo et al. 1978). The addition of a metabolic activator 

(S9 fraction) or glutathione increased both the number of aberrations and the toxicity of sodium selenite 

(Whiting et al. 1980) and sodium selenate (Lo et al. 1978; Whiting et al. 1980). 

Sodium selenite, sodium selenide, methylselenocyanate, and Se-methylselenocysteine were all found to 

be cytotoxic to cells of a mouse mammary carcinoma line; however, only sodium selenite and sodium 

selenide induced DNA strand breaks (Lu et al. 1995b). 

Selenomethionine (Khalil 1989) and selenocystine (Khalil 1994) have tested positive for sister chromatid 

exchanges in cultured human lymphocytes. Selenomethionine, sodium selenite, and sodium selenate 

tested positive for chromosomal aberrations in cultured human lymphocytes (Biswas 1997; Biswas et al. 

2000; Khalil 1989). Sodium selenite was considerably more clastogenic than sodium selenate (Biswas et 

al. 2000). 

The genotoxicity of selenium monosulfide was assessed in an in vivo/in vitro micronucleus and 

chromosome aberration assay in rats (Moore et al. 1996b). Male Wistar rats (4/dose) were administered 

25, 50, or 100 mg/kg selenium monosulfide in corn oil. Negative control rats received corn oil by gavage 

and positive controls were injected intraperitoneally with 20 mg/kg cyclophosphamide. Animals were 

sacrificed 24 hours after treatment and the femur marrow and spleen were removed and cultured. Spleen 
SELENIUM 134 

3. HEALTH EFFECTS 

and marrow cultures were examined 24 or 48 hours after establishment, respectively. No increase in 

chromosome aberrations or micronucleus formation in cells from treated rats was observed. 

Results of in vivo genotoxicity tests have been both negative and positive (Table 3-5). Chromosomal 

aberrations and sister chromatid exchanges in lymphocytes were not increased in nine neuronal ceroid 

lipofuscinosis patients treated with intramuscular sodium selenite injections or tablets (0.005–0.05 mg 

selenium/kg/day) for 1–13.5 months, or in five healthy persons given selenite (0.025 mg/kg/day) for 

2 weeks (Norppa et al. 1980a). Among the treated patients, there was no distinction between route of 

exposure. 

Compared to untreated controls, a significant increase in the number of micronuclei was observed in bone 

marrow cells of macaques treated by nasogastric intubation with L-selenomethionine at a dose of 0.24 mg 

selenium/kg/day for 15 days (Choy et al. 1989). No effect on the number of micronuclei was observed in 

macaques treated with L-selenomethionine at a dose of 0.12 mg selenium/kg/day for 19 days. A 

significant increase in the number of micronuclei in bone marrow cells was not observed in the offspring 

of macaques treated by nasogastric intubation with L-selenomethionine at a dose of 0.12 mg 

selenium/kg/day on gestation days 20–50 (Choy et al. 1993). The doses of L-selenomethionine used in 

these studies produced obvious signs of toxicity (loss of body weight, poor appetite, constipation, 

depression, weakness) in the macaques. 

Chromosomal aberrations were not increased in the lymphocytes of rats given two intravenous doses of 

sodium selenite at 2.3–2.7 mg selenium/kg (Newton and Lilly 1986). Chromosomal aberrations in bone 

marrow cells were significantly increased in these rats, but the total dose of selenium was near the 

intravenous LD50 for selenite, which has been reported as 5.7 mg selenium/kg in rats (Olson 1986). 

Bone marrow cells of male mice gavaged with sodium selenate or sodium selenite showed a significant 

increase in chromosome breaks and spindle disturbances compared with untreated controls (Biswas et al. 

1997, 1999a). The number of chromosomal aberrations increased with dose and was slightly greater with 

sodium selenite than with sodium selenate. A significant increase in micronucleus formation was 

observed in bone marrow cells of male mice intraperitoneally injected with selenous acid and in female 

mice intramuscularly injected with sodium selenite, but not in male mice intraperitoneally injected with 

sodium selenate (Itoh and Shimada 1996; Rusov et al. 1996). 
SELENIUM 135 

3. HEALTH EFFECTS 

Selenium appears to affect the ability of liver enzymes to activate some chemical mutagens. Studies in 

animals exposed orally to sodium selenite in the diet at doses between 0.05 and 0.125 mg 

selenium/kg/day indicate that selenium may inhibit the mutagenic effect of other chemical agents (Gairola 

and Chow 1982; Schillaci et al. 1982). In these studies, S. typhimurium was used to assess the 

mutagenicity of DMBA, benzo[a]pyrene (BAP), and 2-aminoanthracene (2AA) in the presence of liver 

microsomal enzymes from rats fed either a basal diet (0.02–0.15 mg selenium/kg diet or 0.001–0.0075 mg 

selenium/kg/day) or a sodium selenate-supplemented diet (basal diet plus 1–5 mg selenium/kg/diet or 

0.05–0.25 mg selenium/kg/day) for 3–20 weeks. DMBA and 2AA were found to be less mutagenic in the 

presence of liver microsomal enzymes taken from rats fed the selenium-supplemented diets than in the 

presence of microsomal enzymes taken from rats fed the basal diet; BAP mutagenicity was not changed. 

The genotoxicity of selenium monosulfide was assessed in in vivo micronucleus and chromosome 

aberration assays in rats (Moore et al. 1996b). Male Wistar rats (5/dose/timepoint) were administered 

12.5, 25, or 50 mg/kg selenium monosulfide in corn oil. Negative control rats received corn oil by gavage 

and positive controls were injected intraperitoneally with 20 mg/kg cyclophosphamide. Animals were 

sacrificed 24, 36, or 48 hours after treatment and the femur marrow and spleen cells were examined. A 

small, but significant increase in micronucleated bone marrow cells was observed 24 hours after treatment 

with 50 mg/kg selenium monosulfide and 48 hours after treatment with 12.5 mg/kg selenium 

monosulfide. Selenium monosulfide was cytotoxic at the 50 mg/kg dose after 24 hours. No increase in 

micronucleus formation was observed in the spleen. No increase in chromosome aberrations was 

observed in the bone marrow or spleen. 

3.4 TOXICOKINETICS 

Occupational studies indicate that humans absorb elemental selenium dusts and other selenium 

compounds, but quantitative inhalation toxicokinetic studies in humans have not been done. Studies in 

dogs and rats indicate that following inhalation exposure, the rate and extent of absorption vary with the 

chemical form of selenium. Studies in humans and experimental animals indicate that, when ingested, 

several selenium compounds including selenite, selenate, and selenomethionine are readily absorbed, 

often to greater than 80% of the administered dose. Although a study of humans did not detect evidence 

of dermal absorption of selenomethionine, one study of mice indicates selenomethionine can be absorbed 

dermally. There is little or no information available on the absorption of selenium sulfides, but selenium 

disulfides are not believed to be absorbed through intact skin. 
SELENIUM 136 

3. HEALTH EFFECTS 

Selenium accumulates in many organ systems in the body; in general, the highest concentrations are 

found in the liver and kidney (Table 3-6). Selenium concentrations in tissues do not seem to be correlated 

with effects. Tissue concentrations were highest in pigs fed D,L-selenomethionine, while a similar dose 

of selenium (form not stated) given as A. bisulcatus was a more potent neurotoxin. Blood, hair, and nails 

also contain selenium, and selenium has been found in human milk (Table 3-7). In addition, selenium is 

subject to placental transfer. 

As a component of glutathione peroxidase and the iodothyronine 5'-deiodinases, selenium is an essential 

micronutrient for humans. Its role in the deiodinase enzymes may be one reason that growing children 

require more selenium than adults. Selenium is also a component of the enzyme thioredoxin reductase, 

which catalyses the NADPH-dependent reduction of the redox protein thioredoxin. Other seleniumcontaining proteins of unknown functions, including selenoprotein P found in the plasma, have also been 

identified. Excess selenium administered as selenite and selenate can be metabolized to methylated 

compounds and excreted. 

Selenium is primarily eliminated in the urine and feces in both humans and laboratory animals. The 

distribution of selenium between the two routes seems to vary with the level of exposure and time after 

exposure. The form of selenium excreted is dependent on the form of selenium that was ingested. In 

cases of acute exposure to toxic concentrations of selenium or selenium compounds, significant amounts 

of selenium can be eliminated in the breath, causing the characteristic "garlic breath." 

A number of metabolism and other toxicokinetic studies of selenium are nutritional studies designed to 

answer a nutritional question, not a toxicological question. For example, the dose used may not be toxic, 

but may be meant to provide information on how a dose relevant to selenium deficiency or cancer 

chemoprevention might be handled in the body. Since the metabolism of selenium is a function of the 

dose ingested, these studies may be of limited toxicological relevance. 

3.4.1 Absorption 

3.4.1.1 Inhalation Exposure 

Studies regarding the absorption of selenium in humans following inhalation exposure are limited to 

occupational studies. Glover (1970) examined urinary selenium levels of workers employed in a 
SELENIUM 137 

3. HEALTH EFFECTS 

Table 3-6. Selenium Concentrations in Human Tissuesa,b 

Selenium concentration 

Mean SD 

Fetal tissues 

Range Country Reference 

Liver (μg selenium/g)

 2.8 0.2 United States Robkin et al. 1973c 

Blood (mg selenium/L)

 0.12 

1.04 

0.008 

0.28 

United States 

United States 

Hadjimarkos et al. 1959 

Baglan et al. 1974c 

0.070 0.017 New Zealand Thompson and Robinson 1980 

0.061 0.014 Scandinavia Korpela et al. 1984 

Erythrocytes (mg selenium/L)

 0.39 0.08 United States Rudolph and Wong 1978 

0.149 Scandinavia Haga and Lunde 1978 

0.104 0.026 New Zealand Thompson and Robinson 1980 

Plasma (mg selenium/L)

 0.13 0.03 United States Rudolph and Wong 1978 

0.033 0.008 New Zealand Thompson and Robinson 1980 

Serum (mg selenium/L)

 0.052 Scandanavia Haga and Lunde 1978 

Adult/Infant tissues 

Adrenal gland (μg selenium/g)

 0.46 

 0.21 (infant) 

 0.36 (adult) 

0.03 

Brain (μg selenium/g)

United States 

Canada 

Blotcky et al. 1979 

Dickson and Tomlinson 1967 

0.11 

 0.16 (infant) 

 0.27 (adult) 

0.021 0.114–0.171 

0.115–0.222 

Denmark 

Germany 

Canada 

Japan 

Larsen et al. 1979 

Oster et al. 1988c 

Dickson and Tomlinson 1967 

Ejima et al. 1996 

Fat (μg selenium/g)

 0.09 (infant) 

 0.12 (adult) 

Gonad (μg selenium/g)

Canada Dickson and Tomlinson 1967 

 0.46 (infant) 

 0.47 (adult) 

Canada Dickson and Tomlinson 1967 
SELENIUM 138 

3. HEALTH EFFECTS 

Table 3-6. Selenium Concentrations in Human Tissuesa,b 

Selenium concentration 

Mean SD Range Country Reference 

Heart (μg selenium/g)

 0.33 0.13 

0.170 0.032 

0.155 0.030 (LV) 

0.55 (infant) 

0.22 (adult) 

Intestine (μg selenium/g)

 0.31 (infant) 

0.22 (adult) 

Kidney (μg selenium/g)

 0.89 0.11 

0.771 0.169 

0.92 (infant) 

0.63 (adult) 

0.78 0.19 

Liver (μg selenium/g)

 0.62 0.04 

0.50 0.08 

1.73 0.24 

0.291 0.078 

0.995 0.308 

0.45 0.11 

0.06 

0.33 0.12 

0.19 0.05 

0.34 (infant) 

0.39 (adult) 

Lung (μg selenium/g)

 0.30 0.02 

0.132 0.033 

0.17 (infant) 

0.21 (adult) 

Pancreas (μg selenium/g)

 0.55 0.13 

0.63 0.07 

0.05 (infant) 

0.13 (adult) 

0.36–1.29 

0.35–0.65 

0.27–0.51 

0.082–0.64 

0.10–0.27 

United States 

Germany 

Canada 

Canada 

United State 

Germany 

Canada 

Sweden 

United States 

United States 

United States 

Denmark 

Germany 

Finland 

Finland 

Bulgaria 

Sweden 

New Zealand 

Canada 

United States 

Germany 

Canada 

United States 

United States 

Canada 

Blotcky et al. 1979 

Oster et al. 1988c 

Dickson and Tomlinson 1967 

Dickson and Tomlinson 1967 

Blotcky et al. 1979 

Oster et al. 1988c 

Dickson and Tomlinson 1967 

Muramatsu and Parr 1988 

Blotcky et al. 1979 

Zeisler et al. 1984 

McConnell et al. 1975c 

Larsen et al. 1979 

Oster et al. 1988c 

Alfthan et al. 1991c 

Aaseth et al. 1990 

Damyanova 1983 

Muramatsu and Parr 1988 

Casey et al. 1983 

Dickson and Tomlinson 1967 

Blotcky et al. 1979 

Oster et al. 1988c 

Dickson and Tomlinson 1967 

Blotcky et al. 1979 

McConnell et al. 1975c 

Dickson and Tomlinson 1967 
SELENIUM 139 

3. HEALTH EFFECTS 

Table 3-6. Selenium Concentrations in Human Tissuesa,b 

Selenium concentration 

Mean SD Range Country Reference 

Prostate (μg selenium/g)

 0.26 0.02 

0.150 0.035 

Skeletal muscle (μg selenium/g)

 0.40 0.20 

0.111 0.017 

0.31 (infant) 

0.40 (adult) 

Skin (μg selenium/g)

 0.24 0.02 

Spleen (μg selenium/g)

 0.37 0.03 

0.226 0.044 

0.37 (infant) 

0.27 (adult) 

Stomach (μg selenium/g)

 0.19 (infant) 

0.17 (adult) 

Testis (μg selenium/g)

 0.28 0.03 

0.274 0.048 

Thyroid (μg selenium/g)

 1.02 0.20 

0.72 0.44 

0.64 (infant) 

1.24 (adult) 

United States 

Germany 

Blotcky et al. 1979 

Oster et al. 1988c 

United States 

Germany 

Canada 

Blotcky et al. 1979 

Oster et al. 1988c 

Dickson and Tomlinson 1967 

0.13–0.21 Denmark Larsen et al. 1979 

United States Blotcky et al. 1979 

United States 

Germany 

Canada 

Blotcky et al. 1979 

Oster et al. 1988c 

Dickson and Tomlinson 1967 

Canada Dickson and Tomlinson 1967 

United States 

Germany 

Blotcky et al. 1979 

Oster et al. 1988c 

0.15–1.90 

United States 

Finland 

Canada 

Blotcky et al. 1979 

Aaseth et al. 1990 

Dickson and Tomlinson 1967 

a

General population measures unless otherwise noted 

b

Selenium concentrations in adult blood and blood components, urine, hair, nails, milk, placenta, and semen are 

found in Table 3-7. 

c

Dry weight 

LV = left ventricle; RV = right ventricle; SD = standard deviation 
SELENIUM	 140 

3. HEALTH EFFECTS 

Table 3-7. Biomarkers: Selenium Concentrations in Human Tissues and Fluidsa 

Selenium concentration 

Mean SD Range Country Reference 

Whole blood (mg selenium/L) 

0.132 0.029 0.08–0.13 

0.206 0.10–0.30 

0.109 0.015 

0.157	 0.103–0.191 

0.182 0.037 

0.095 0.009 

0.095 0.091 

0.164 0.032 

0.108	 0.006 0.076–0.140 

0.079–0.103 

0.080–0.089 

0.077–0.089 

0.069 0.018 

0.059 0.012 

0.092 0.001 0.06–0.013 

Erythrocyte (mg selenium/L) 

0.174 0.11–0.28 

0.13 0.02 

0.52 0.05 

0.131 0.002 0.060–0.210 

0.057–0.087 

0.074 0.016 

0.103 0.030 

Plasma (mg selenium/L) 

0.155 0.081–0.225 

0.095 0.016 

0.21 0.03 

0.148 

0.081 0.016 

0.153 0.021 

0.089 0.014 

0.081 0.001 0.056–0.105 

0.118 0.027 0.064–0.173 

0.048 0.010 

0.041 0.011 

United States 

United States 

United States 

United States 

Canada 

China 

China 

Greece 

Italy 

Finland 

Finland 

Finland 

New Zealand 

New Zealand 

Germany 

United States 

United States 

United States 

Germany 

New Zealand 

New Zealand 

New Zealand 

United States 

United States 

United States 

United States 

Canada 

Japan 

Netherlands 

Italy 

Italy 

New Zealand 

New Zealand 

Corden et al. 1989 

Allaway et al. 1968 

Dworkin et al. 1986 

Shamberger 1983 

Dickson and Tomlinson 1967 

Zhu 1981 

Yang et al. 1983 

Bratakos et al. 1990

Minoia et al. 1990 

Jaakkola et al. 1983 

Kumpusalo et al. 1990b 

Kumpusalo et al. 1990c 

Thomson and Robinson 1980d 

Rea et al. 1979 

Oster et al. 1988b 

Meyer and Verreault 1987 

Dworkin et al. 1986 

Rudolph and Wong 1978d 

Oster et al. 1988b 

Watkinson 1981 

Rea et al. 1979 

Thomson and Robinson 1980 

Clark et al. 1984 

Dworkin et al. 1986 

Rudolph and Wong 1978d 

Coates et al. 1988 

Dickson and Tomlinson 1967 

Hojo 1987 

van’t Veer et al. 1990 

Minoia et al. 1990 

Sesana et al. 1992 

Rea et al. 1979 

Thomson and Robinson 1980d 
SELENIUM 141 

3. HEALTH EFFECTS 

Table 3-7. Biomarkers: Selenium Concentrations in Human Tissues and Fluidsa 

Selenium concentration 

Mean SD Range Country Reference 

Serum (mg selenium/L) 

0.136 

0.110 

0.162 

0.07 

0.125 

0.198 

0.143 

0.081 

0.118 

0.055 

0.073 

0.207 

0.002 

0.016 

1.48 

0.047g 

0.055 

0.016 

0.001 

0.016 

0.001 

0.015 

Urine (mg selenium/L) 

0.034 

0.058 

0.026 

0.024 

0.022 

0.024 

0.026 

0.012 

0.002 

0.002 

Hair (μg selenium/g) 

0.64 

0.359 

0.36 

0.42 

0.42 

3.40 

3.70 

1.02 

0.63 

0.54 

0.77 

0.02 

0.004 

0.17 

0.88 

0.10 

2.0 

2.3 

1.04 

0.52 

0.34 

0.24 

Nails (μg selenium/g) 

1.56 

0.82 

0.63 

0.54 

0.78 

0.58 

0.174 

0.12 

0.91 

0.123–0.363 

0.033–0.121 

0.087–0.093 

0.087–0.308 

0.07–0.81 

0.229–0.621 

0.020–0.113 

0.002–0.031 

0.21–0.63 

0.95–9.6 (female) 

0.06–14.2 (male) 

Maternal 

Neonatal 

Maternal 

Child 

0.083–3.82 

0.085–2.75 

United States 

United States 

United States 

United States 

United States 

United States 

Canada 

Italy 

Italy 

Finland 

Finland 

South Africa 

Venezuela 

Venezuela 

England 

Japan 

China 

Greece 

Italy 

United States 

China 

China 

Greece 

Sweden 

Japan 

England 

Spain 

United States 

United States 

Netherlands 

Greece 

Netherlands 

Willett et al. 1983 

Menkes et al. 1986 

Coates et al. 1988 

McConnell et al. 1975e 

DHHS 1997 

Longnecker et al. 1991 

Lalonde et al. 1982f
 

Minoia et al. 1990 

Morisi et al. 1989 

Luoma et al. 1992 

Virtamo et al. 1987 

Heese et al. 1988d
 

Brätter et al. 1991a 

Brätter and Negretti De Brätter 1996
 

Glover 1970 

Hojo 1981a 

Yang et al. 1983 

Bratakos et al. 1990 

Minoia et al. 1990
 

Thimaya and Ganapathy 1982 

Zhu 1981 

Yang et al. 1983 

Bratakos et al. 1990 

Muramatsu and Parr 1988e
 

Imahori et al. 1979e 

Razagui and Haswell 1997
 

Bermejo Barrera et al. 2000
 

Longnecker et al. 1991 

Hunter et al. 1990a 

van’t Veer et al. 1990 

Bratakos et al. 1990 

Van Noord et al. 1992
 
SELENIUM 142 

3. HEALTH EFFECTS 

Table 3-7. Biomarkers: Selenium Concentrations in Human Tissues and Fluidsa 

Selenium concentration 

Mean SD Range Country Reference 

Milk (μg selenium/mL) 

Africa Funk et al. 1990b 

United States Shrearer and Hadjimarkos 1975 

United States Hadjimarkos 1963 

Smith et al. 1990 

United States Ellis et al. 1990 

Chile Cortez 1984 

Finland Kumpulainen 1983 

Austria Li et al. 1999 

Germany Michalke and Schramel 1998 

Venezuela Brätter et al. 1991a 

Venezuela Brätter and Negretti De Brätter 1996 

United States Baglan et al. 1974e 

United States Korpela et al. 1984 

United States Hadjimarkos et al. 1959 

Singapore 

Finland 

Roy et al. 1990 

Suistomaa et al. 1987e 

0.018 0.004 

0.021 

0.016 0.005 

0.026 

0.062 0.055 

0.010 0.002 

0.011 

0.012 

Placenta (mg selenium/L) 

1.70 0.61 

0.193 0.016 

0.18 0.007 

Semen (μg selenium/g) 

0.063 0.020 

1.80 0.11 

0.208–0.256 

0.007–0.033 

0.013–0.053 

0.015–0.214 

0.006–0.013 

0.025–0.250 

0.043–0.112 

0.016–0.131 

a

General population measures unless otherwise noted 

b

Range of mean concentration 

c

Range of mean concentrations for multivitamin users 

d

Only women were sampled. 

e

Dry weight 

f

Only men were sampled. 

g

Standard error of the mean 

SD = standard deviation 
SELENIUM 143 

3. HEALTH EFFECTS 

selenium rectifier plant. Workers exposed to higher levels of unspecified inorganic selenium compounds 

in the air excreted higher levels of selenium in their urine than workers in other areas of the plant with 

lower concentrations of selenium in the air. Although the study indicates that selenium was absorbed 

from the lungs of the workers, the nonspecific exposure levels and lack of compound identification 

precluded an estimate of the extent and rate of absorption from the lungs. Significantly increased serum 

selenium levels were reported for workers at a rubber tire repair shop in Toluca City, Mexico compared 

with a group of unexposed individuals from the same city (Sánchez-Ocampo et al. 1996). The workers in 

this study were exposed to selenium (no levels reported) from vulcanized rubber, both as dust in the air 

and from handling the tires; thus, it is not possible to attribute absorption to a single route. 

Studies using dogs and rats indicate that absorption of selenium following inhalation exposure is 

extensive, although the rate of absorption depends on the chemical form of selenium. In rats (Medinsky 

et al. 1981a) and dogs (Weissman et al. 1983), the absorption of selenium following inhalation exposure 

to selenious acid aerosol is approximately twice as rapid as the absorption of selenium following 

inhalation exposure to elemental selenium aerosol. However, Medinsky et al. (1981a) found that with 

either form after 4 days most of the selenium was absorbed following inhalation exposure and that the 

distribution of selenium in the body tissues was identical, suggesting that selenium entered the same body 

pool following pulmonary uptake (Medinsky et al. 1981a). 

3.4.1.2 Oral Exposure 

Selenium compounds are generally readily absorbed from the human gastrointestinal tract. The bioavailability of ingested selenium can be affected by the physical state of the compound (e.g., solid or solution), 

the chemical form of selenium (e.g., organic, inorganic), and the dosing regimen. However, in general, it 

appears that the degree of selenium absorption (i.e., percent of administered dose absorbed) in humans is 

independent of the exposure level, but that in some cases, absorption is greater when selenium deficiency 

exists. 

In humans, absorption of sodium selenite or selenomethionine can exceed 80% for both small and 

relatively large doses (Griffiths et al. 1976; Thomson 1974; Thomson and Stewart 1974; Thomson et al. 

1977). A total of 90–95% of a small amount of sodium selenite (0.010 mg selenium/person) administered 

in aqueous solution was absorbed (Thomson 1974). Absorption of a large dose (1.0 mg/person) of either 
SELENIUM 144 

3. HEALTH EFFECTS 

sodium selenite or selenomethionine was 90–95 and 97% of the administered dose, respectively 

(Thomson et al. 1977). These data indicate a lack of homeostatic control over the dose range tested. 

Martin et al. (1989a) found no clear evidence of increased gastrointestinal absorption of selenium as 

sodium selenite in aqueous solution by healthy male volunteers kept on a selenium-deficient diet. 

Griffiths et al. (1976) reported 96–97% absorption of a single dose of 0.002 mg selenium administered as 

selenomethionine in solution. Similarly, Thomson et al. (1977) reported 97% absorption of a single large 

dose of 1.0 mg selenium administered as selenomethionine in solution to one subject. The subjects in 

these studies were New Zealand women. 

Other studies have indicated that humans might absorb selenomethionine more efficiently than sodium 

selenite (Moser-Veillon et al. 1992; Swanson et al. 1991). Young et al. (1982) studied human absorption 

of dietary selenium in young men in the United States. The men ate either 75Se-labeled chicken alone 

(0.013 mg selenium/person) or the chicken plus supplemental labeled sodium selenite (0.071 mg 

selenium/person in a solution mixed with the meal). Eighty percent of the selenium in the chicken meat 

was absorbed, but less than 30% of the selenium administered as sodium selenite was absorbed. 

Similarly, Robinson et al. (1978) found that 75% of selenomethionine, but only 46% of selenite, was 

absorbed during a 10–11-week administration of solutions providing 0.0013–0.0023 mg selenium/kg/day 

to New Zealand women. It is not clear why the estimated absorption of sodium selenite varied between 

46 and 30% in these trials. 

Experimental animals also efficiently absorb selenium compounds from the gut independent of the level 

of selenium exposure. Several studies have reported absorption of 80–100% in rats given dietary 

selenium administered as sodium selenite, sodium selenate, selenomethionine, or selenocystine (Furchner 

et al. 1975; Thomson and Stewart 1973). Other animal species also readily absorb orally administered 

selenium compounds. Furchner et al. (1975) estimated that over 90% of an oral dose of selenious acid 

was absorbed in mice and dogs, although monkeys absorbed less of the administered dose (amount 

unspecified). Using an in vivo perfusion method in which selenite was added directly to the duodenal end 

of the small intestine, the absorption of selenite was linearly related to concentration (slope=0.0386) in 

the range of 1–200 μM (Chen et al. 1993). 

In one study of rats, absorption of selenite or selenomethionine into the blood stream following oral 

exposure occurred primarily in the duodenum and, to a lesser extent, in the jejunum and ileum (Whanger 

et al. 1976). Compared to the small intestine, little selenium was absorbed from the stomach (Whanger et 

al. 1976), and it was not determined whether absorption occurred in the large intestine. In an in vitro 
SELENIUM 145 

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study using everted intestinal sacs from hamsters, Spencer and Blau (1962) found that selenomethionine 

was transported against a concentration gradient with the same characteristics as methionine. 

Selenomethionine was not found to be degraded during transport. This study suggests that in the 

intestines, methionine and selenomethionine share the same transport mechanism. 

A comparison of absorption of selenium by selenium-depleted rats after oral administration of sodium 

selenate, selenomethionine, or methyl selenocysteine (from high-selenium broccoli) found that gross 

absorption of selenium from methyl selenocysteine was significantly lower (85%) than from sodium 

selenate or selenomethionine (91%); further, true selenium absorption adjusted for urinary excretion was 

significantly different for methyl selenocysteine, sodium selenate, and selenomethionine, with the lowest 

absorption for methyl selenocysteine and the highest for selenomethionine (Finley 1998). Absorption of 

selenium from selenomethionine was not significantly lower than from sodium selenate. 

In vivo experiments with ligated rat intestines have shown that there is significantly higher absorption and 

transfer to the body of selenium as selenocystine or selenodiglutathione than selenium as selenite from 

ligated loops of ileum, but that absorption of the three forms of selenium in the jejunum was 

approximately similar (Vendeland et al. 1992). In vitro experiments with brush border membrane 

vesicles derived from rat intestines have shown dramatic differences in the uptake and binding of 

selenium depending on the form in which it is presented, with absorption of organic forms being much 

more efficient than absorption from selenite or selenate (Vendeland et al. 1992, 1994). Selenium from 

selenocystine or selenodiglutathione was absorbed 10 times more quickly than selenium from sodium 

selenite (Vendeland et al. 1992). Similarly, selenium was much more efficiently absorbed from 

selenomethionine than from selenite or selenate (Vendeland et al. 1994). Binding also varied between 

selenomethionine, selenite, and selenate, with selenite binding exceeding that of selenate by 37-fold and 

selenomethionine exceeding selenite by 14-fold (Vendeland et al. 1994). These studies indicate that 

absorption of selenium from the gastrointestinal tract of animals is pH-dependent and influenced by the 

presence of sulfhydral-containing compounds, and that the increased absorption of selenium with 

sulfhydral compounds is likely due to complex formation with these compounds. 

3.4.1.3 Dermal Exposure 

Dermal absorption was tested in eight women at a maximum dose of 0.0029 mg selenium/kg as 

selenomethionine (0.05% L-selenomethionine in a lotion). No detectable increase in serum selenium 

concentrations was observed, but because the concentrations tested were so low, absorption cannot be 
SELENIUM 146 

3. HEALTH EFFECTS 

ruled out (Burke et al. 1992a). Absorption of selenium disulfide was examined using a monthly 24-hour 

urine specimen in 16 persons who washed their hair weekly with a 1% selenium disulfide shampoo. No 

differences were found from control urinary selenium levels over the 1-year exposure period (Cummins 

and Kimura 1971). No absorption of selenium from selenium sulfide was seen in 15 persons who applied 

a 2.5% selenium sulfide suspension to their torsos and allowed it to remain on the body overnight 

(Kalivas 1993). 

Mice were treated with a maximum of 0.02% selenium as selenomethionine by topical application of a 

lotion 3 times per week for 39 weeks to the shaved back and ears (size of area not specified). The applied 

dose was 0.29 mg/kg/day. Controls received the lotion without selenium. Dermal effects were not 

observed in the selenomethionine-treated mice. However, treated animals had significantly higher 

concentrations of selenium than the controls in the liver and ventral skin away from the application site 

(Burke et al. 1992b). These data suggest that mice can absorb topically applied selenomethionine, but 

since the areas were not occluded, some oral absorption during grooming is also possible. 

3.4.2 Distribution 

Most studies report similar distribution patterns for both organic and inorganic selenium compounds 

tested. In plasma, selenium mainly distributes into three plasma proteins, namely selenoprotein P, 

glutathione peroxidase, and albumin (Ducros et al. 2000). Approximately 3% of total plasma selenium is 

bound to lipoproteins, mainly to the LDL fraction, and the selenium may be incorporated as 

selenomethionine in place of methionine during protein synthesis and/or bound to cysteine residues by 

selenium-sulfur bonds. Selenoprotein P is an extracellular protein in the plasma. It is suggested that 

selenoprotein P is involved in the transport of selenium and as an antioxidant, but its biochemical function 

has not yet been established (Burk and Hill 2000; Hill and Burk 1989; Yang et al. 1989b). 

Normal levels of selenium found in various human tissues are shown in Table 3-6. Selenium 

concentrations in human fluids and tissues that are easily collected (e.g., placenta) are provided in 

Section 3.8.1, Biomarkers Used to Identify or Quantify Exposure to Selenium. Selenium from sodium 

selenite and sodium selenate is found at the highest concentrations in the liver and kidney of humans and 

other animals following oral administration or intravenous or subcutaneous injection (Cavalieri et 

al. 1966; Heinrich and Kelsey 1955; Jereb et al. 1975; Thomson and Stewart 1973). Similarly, monkeys 

receiving high doses of L-selenomethionine orally for up to 30 days accumulated the highest 
SELENIUM 147 

3. HEALTH EFFECTS 

concentrations of selenium in the liver and kidneys (Willhite et al. 1992). Selenium from 

selenomethionine tends to be retained in tissues at higher concentrations (3–10-fold greater) and for 

longer periods of time than inorganic selenium compounds. The increased selenium tissue concentrations 

are not due to the slightly greater absorbance of selenomethionine (Butler et al. 1990; Grønbaek and 

Thorlacius-Ussing 1992; Ip and Hayes 1989; Salbe and Levander 1990b), but rather to the slower 

elimination as a consequence of its incorporation into body proteins (Stadtman 1983, 1987, 1990). 

3.4.2.1 Inhalation Exposure 

No studies were located regarding the distribution of selenium in humans after inhalation of elemental 

selenium or selenium compounds. 

Weissman et al. (1983) reported that selenium concentrated in the liver, kidney, spleen, and lungs of dogs 

following inhalation exposure to selenious acid or elemental selenium aerosols. 

3.4.2.2 Oral Exposure 

A study of 100 paired samples of maternal and neonate hair found that the concentration in neonatal hair 

(0.63±0.52 μg/g) was lower than in maternal hair (1.02±1.04 μg/g), but the results were not analyzed 

statistically (Razagui and Haswell 1997). Levels of selenium in 30 paired samples of the hair of a mother 

and her child found no correlation between the selenium concentration of the hair of the mother and her 

child (Bermejo Barrera et al. 2000). The average level of selenium in the children’s hair (0.77±0.24 μg/g) 

was higher than that of their mothers (0.54±0.34 μg/g). The higher concentration of selenium in the 

children’s hair could represent increased absorption or retention, but no information was provided in the 

study as to the age of the children or to possible differences in dietary intake of selenium between mother 

and child. 

A study in rats found that young (weanling) animals accumulated more selenium in their tissues than 

adults (Salbe and Levander 1989). Selenium-deficient rats were fed diets supplemented with the same 

amounts of selenium, as sodium selenate or L-selenomethionine, for 4 weeks. Hair and nail selenium 

levels in adults were 10–20% and ~50% lower, respectively, than the amounts found in weanlings. 

Skeletal muscle and red blood cell selenium levels were ~50 and ~35% lower, respectively, in adults than 

weanlings, whereas levels in the liver were generally similar between the two growth phases. 
SELENIUM 148 

3. HEALTH EFFECTS 

Selenomethionine caused greater deposition of selenium in the tissues than sodium selenate in both adults 

and weanlings, although the percent increase was similar for the two compounds in both growth phases. 

In rats and dogs, the selenium arising from sodium selenite administered in drinking water or in the diet is 

widely distributed in the body, although concentrated primarily in the liver and kidney (Furchner et al. 

1975; Sohn et al. 1991; Thomson and Stewart 1973). 

In most studies, selenium from selenomethionine accumulates in tissues to a greater extent than equal 

administered doses of selenium from selenite or selenate. Behne et al. (1991) reported higher liver and 

muscle selenium concentrations in rats receiving selenium orally as selenomethionine for 3 or 6 weeks 

than as selenite for the same length of time. Ip and Hayes (1989) reported similar results for blood, liver, 

kidney, and skeletal muscle. Salbe and Levander (1990b) compared distribution of dietary selenomethionine and selenate in rats and found higher selenium concentrations in plasma, erythrocytes, liver, 

muscle, hair, and nails in animals receiving selenomethionine. (Hair and nails have been used to gauge 

long-term human selenium exposure and were, therefore, included in this study.) Monkeys receiving 

selenomethionine in drinking water for 11 months had selenium concentrations in plasma, erythrocytes, 

liver, muscle, and hair that were 3–10-fold greater than monkeys receiving selenite (Butler et al. 1990). 

The higher levels of selenium found after selenomethionine compared to selenite treatment are likely a 

result of a greater retention of selenium from selenomethionine, rather than a difference in absorption. 

Butler et al. (1990) indicate that dietary ascorbic acid can reduce selenite absorption, but not 

selenomethionine absorption. Therefore, the differential effect of ascorbic acid on selenium absorption 

may have contributed to the difference in selenium content of tissues observed in monkeys treated with 

selenite, compared to monkeys treated with selenomethionine. Studies of rats indicate that the central 

nervous system also concentrates more selenium when administered as selenomethionine than when 

administered as inorganic selenium compounds (Grønbaek and Thorlacius-Ussing 1989, 1992; Zi-Jian Jie 

1992). 

A comparison of distribution of selenium in selenium-depleted rats after oral administration of sodium 

selenite, sodium selenate, selenomethionine, or methyl selenocysteine (from high-selenium broccoli) 

revealed that the rate of restoration of selenium in the liver and muscle was significantly slower for 

methyl selenocysteine than other forms of selenium (Finley 1998). The rate of repletion in muscle was 

significantly faster for selenomethionine than other groups, but kidney and plasma showed no significant 

difference in the rate of repletion for any form of selenium. The rate of repletion of glutathione 

peroxidase activity in the tissues was similar to the rate of repletion of the tissue itself and was slowest 

when methyl selenocysteine was the administered form. 
SELENIUM 149 

3. HEALTH EFFECTS 

Another study of distribution of selenium in selenium-deficient rats fed either sodium selenite or 

selenomethionine found that the concentration of selenium in blood and hair increased with administered 

dose, but was higher for selenium administered as selenomethionine (Shiobara et al. 1998). 

A study of dietary supplementation of female pigs with 0.1 or 0.3 ppm selenium from a seleniumenriched yeast or from sodium selenite (doses not given) from 60 days before breeding until weaning 

found that the concentration of selenium in milk, dam, and offspring tissues increased with the dose of 

selenium administered and was higher when the source of selenium was the selenium-enriched yeast 

(Mahan and Kim 1996). 

A study using pigs indicates that tissue levels of selenium do not correlate with effects. Tissue 

concentrations of selenium were higher in pigs fed 1.25 mg selenium/kg/day as D,L-selenomethionine 

than in pigs fed the same dose of selenium as A. bisulcatus or selenate, although neurological effects were 

more severe and occurred after fewer days of treatment with A. bisulcatus (Panter et al. 1996). The form 

of selenium in A. bisulcatus is unknown, although Panter et al. (1996) indicate that it is nonprotein. 

In poultry, selenium is concentrated in the pancreas to a greater extent following oral administration of 

selenomethionine than following oral administration of sodium selenite (Cantor et al. 1975). The 

differential ability of the two compounds to concentrate in the pancreas of birds may explain why 

selenium administered as selenomethionine is more effective than the same dose of selenium 

administered as sodium selenite in preventing pancreatic fibrosis in chicks, a condition indicative of 

selenium deficiency (Cantor et al. 1975). 

The distribution profiles of single oral or intravenous doses of selenium (2 mg selenium/kg as sodium 

selenite) administered to Wistar rats were dependent on the route of administration (Kaneko et al. 1999). 

Selenium concentration was highest in the kidney or liver, followed by the heart, lung, or spleen; then 

plasma and the brain. Oral administration produced lower doses of selenium than injection in all organs 

except the kidney where levels produced by the two routes were comparable (this may reflect the 

importance of urine as a route of excretion). 

Following oral exposure, selenium is found in human milk (Brätter and Negretti De Brätter 1996; Brätter 

et al. 1991b; Li et al. 1999; Michalke and Schramel 1998; Moser-Veillon et al. 1992; Rodríguez 

Rodríguez et al. 1999; Viitak et al. 1995; Yang 1989b). Selenium is also found in the milk of mice, rats, 
SELENIUM 150 

3. HEALTH EFFECTS 

dogs, pigs, cows, and monkeys (Abdelrahman and Kincaid 1995; Archimbaud et al. 1992; Baňuelos and 

Mayland 2000; Chhabra and Rao 1994; Hawkes et al. 1994; Mahan and Kim 1996; Parizek et al. 1971a). 

This supplies offspring with selenium during the time period in which they are fed exclusively on milk 

(about 6 months for humans). Transplacental transfer of selenium has been demonstrated in humans, rats, 

hamsters, dogs, pigs, and monkeys (Archimbaud et al. 1992; Choy et al. 1993; Hawkes et al. 1994; 

Jandial et al. 1976; Mahan and Kim 1996; Parizek et al. 1971a; Willhite et al. 1990). 

3.4.2.3 Dermal Exposure 

Although unable to detect increased selenium in human females exposed to selenomethionine dermally, 

Burke and coworkers found elevated liver and skin selenium concentrations in mice treated with a topical 

lotion containing selenomethionine applied to the shaved back and ears (size of area not specified), 

although since the areas were not occluded, some oral absorption during grooming is also possible (Burke 

et al. 1992a, 1992b). In rats, between 9 and 27% of dermally applied selenious acid was absorbed, as 

measured in 75Se radioisotope studies (Medinsky et al. 1981b). 

3.4.2.4 Other Routes of Exposure 

In humans, selenium has been found to be widely distributed to organs and tissues following injection of 

sodium selenite, sodium selenate, and selenomethionine, with the highest concentrations generally found 

in the liver and kidneys (Ben-Porath and Kaplan 1969; Cavalieri et al. 1966; Jereb et al. 1975; Lathrop et 

al. 1972). In studies involving injection of radiolabelled selenium, the pancreas accumulated high 

concentrations of radiolabelled selenium immediately following injection, but within hours, the selenium 

rapidly disappeared from this organ (Lathrop et al. 1972). Using an in vitro, dually perfused, human term 

placenta, selenite has also been shown to cross the human placenta (Eisenmann and Miller 1994). 

Further, following intravenous injection, 75Se from selenomethionine was found to cross the near-term 

human placenta (Jandial et al. 1976). 

There is a rapid decline in serum selenium levels 1 hour after intravenous administration of sodium 

selenite or sodium selenate to humans (Burk 1974; Nelp and Blumberg 1965). Burk (1974) found that 

50% of the plasma selenium was protein-bound within the first 2 hours after administration; 85% was 

bound within 4–6 hours after administration; and 95% was bound after 24 hours. Circulating alpha-2 

globulins have been reported to have the greatest affinity for selenium (Hirooka and Galambos 1966a). 
SELENIUM 151 

3. HEALTH EFFECTS 

Burk (1974) found that lipoproteins, primarily the very low density lipoprotein (VLDL) and the lowdensity lipoprotein (LDL) fractions, were also involved in selenium binding. 

In vitro studies of human plasma and whole blood incubated with sodium selenite have indicated that 

selenite is accumulated in erythrocytes by an active transport mechanism (Lee et al. 1969). Several 

studies indicate that the selenite is chemically altered in the erythrocyte and then transported back into the 

plasma, where the selenium metabolite binds to plasma proteins (Burk 1974; Hirooka and Galambos 

1966a; Lee et al. 1969). 

A high degree of protein binding of selenium in the plasma has also been demonstrated in experimental 

animals. Sandholm (1973) found that selenite administered intravenously to mice can be metabolically 

altered by erythrocytes to a form that binds to plasma proteins. In mice, rats, and dogs, selenite initially 

binds to albumin. Later, selenite can be found bound to alpha and gamma globulins in rats and to alpha-2 

and beta-1 globulins in dogs (Imbach and Sternberg 1967; Sternberg and Imbach 1967). 

3.4.3 Metabolism 

The metabolic fate of selenium, an essential element, is outlined in Figure 3-4. In summary, inorganic 

selenium is reduced stepwise to the assumed key intermediate hydrogen selenide, and it (or a closely 

related species) is either incorporated into selenoproteins after being transformed to selenophosphate and 

selenocysteinyl tRNA according to the UGA codon encoding selenocysteinyl residue, or excreted into 

urine after being transformed into methylated metabolites of selenide (Lobinski et al. 2000). 

Consequently, selenium is mainly present in the mammalian body in forms of covalent carbon-selenium 

bonds, particularly selenoprotein P (the principal selenoprotein in plasma), selenoenzymes such as 

glutathione peroxidases (enzymes that catalyze the reduction of peroxidases and thereby protect cells 

from oxidative damage), type 1-iodothyronine deiodinase (which catalyzes the deiodination of thyroxine 

to triiodothyronine), and thioredoxin reductase (which may trigger cell signaling in response to oxidative 

stress) (Holmgren and Kumar 1989; Lobinski et al. 2000). Additional information regarding the 

metabolism of selenium is discussed below. 
SELENIUM 152 

3. HEALTH EFFECTS 

Figure 3-4. Metabolic Pathways for Selenium* 
SELENIUM 153 

3. HEALTH EFFECTS 

Four classes of selenoproteins have been defined (Sunde 1990): selenium-specific proteins, proteins 

incorporating selenocysteine at cysteine codons, proteins incorporating selenomethionine at methionine 

position in those proteins, and proteins that bind selenide nonspecifically. The selenium-specific proteins, 

which include the enzymes glutathione peroxidase, thyroxine reductase, and iodothyronine 5'-deiodinase, 

constitute the most physiologically important class of selenoproteins. These proteins contain 

selenocysteine that is incorporated cotranslationally using selenide and serine as the precursors. This 

process is specified by a uracil-guanine-adenine (UGA) codon, which usually functions as a stop codon. 

A stem-loop structure in the 3' untranslated region is required for UGA to specify selenocysteine (Berry et 

al. 1991). This cotranslational process is the only known pathway for the production of selenocysteine in 

humans. In contrast to selenocysteine, selenomethionine cannot be biosynthesized by human tissues 

(Levander 1986). 

The second and third classes of selenoproteins form in a similar manner: selenomethionine bound to the 

transfer ribonucleic acid (tRNA) for methionine competes with methionine bound to the tRNA for 

methionine at methionine codons, and selenocysteine bound to the tRNA for cysteine competes with 

cysteine bound to the tRNA for cysteine at cysteine codons (Sunde 1990). The amount of selenoamino 

acids incorporated into protein is dependent on the ratio of the selenoamino acid and the amino acid 

bound to the amino acid tRNA. 

The last class of selenoproteins contains the selenium binding proteins. This is an operational class 

defined by Sunde (1990) as "selenoproteins with selenium bound tightly enough so that the selenium 

remains attached during standard protein purification procedures that produce discrete selenium labeled 

species." This class contains selenoproteins that have not been fully characterized. 

As indicated in Figure 3-4, selenide, which can nonspecifically bind to proteins, is a central selenium 

species in the pathways leading to the formation and degradation of selenium proteins. Selenide is also 

formed from selenite by reduction via glutathione following uptake in red blood cells. This reaction 

occurs in rat (Gasiewicz and Smith 1978) and human (Lee et al. 1969) red blood cells, as well as in 

human plasma containing added glutathione (Mas and Sarker 1989). Selenide is then transported to the 

plasma, bound selectively to albumin and transferred to the liver, and methylated for excretion in the 

urine, or incorporated into proteins after being transformed into selenium-phosphate and selenocysteinyl 
SELENIUM 154 

3. HEALTH EFFECTS 

tRNA according to the UGA codon encoding selenocysteinyl residue (Ganther and Lawrence 1997). 

Unlike selenite, selenate appears to be either taken up directly by the liver or excreted in urine by rats 

(Suzuki and Ogra 2002). 

Selenocysteine can also be metabolized to selenide. This reaction requires a specific enzyme, 

selenocysteine β-lyase, which catalyzes the decomposition of selenocysteine to alanine and hydrogen 

selenide. The enzyme requires pyridoxal 5-phosphate as a cofactor. In humans, the highest levels of 

selenocysteine β-lyase activity are found in the liver, followed by the kidney, heart, adrenal gland, and 

muscle (Daher and Van Lente 1992). In mice orally exposed to selenocysteine, an intermediate 

metabolite selenocysteine-glutathione selenyl sulfide is formed in the small intestine and transported to 

the liver via the blood plasma (Hasegawa et al. 1995, 1996b). This compound can be nonenzymatically 

reduced by excess glutathione or enzymatically reduced by glutathione reductase in liver cytosol extracts 

to reform selenocysteine, which can be further metabolized. 

When not immediately metabolized, selenomethionine can be incorporated into tissues such as skeletal 

muscle, liver, pancreas, stomach, gastrointestinal mucosa, and erythrocytes (Schrauzer 2000). 

Selenomethionine metabolism to selenide and the incorporation into selenium-specific proteins may occur 

by two pathways: metabolism to methane selenol and selenide or via selenocysteine. Evidence that the 

incorporation of selenium from selenomethionine into protein is by the transsulfuration pathway 

(methionine to cysteine) comes from studies of selenomethionine metabolism in lymphoblast cell lines 

deficient in cystathionine lyase and cystathionine synthetase, enzymes of the transsulfuration pathway 

(Beilstein and Whanger 1992). Deficiency in these enzymes greatly reduces the incorporation of 

selenomethionine into glutathione peroxidase. 

Similar to metals, elemental selenium, a non-metal, is transformed into methylated metabolites prior to 

being excreted into the urine and/or exhaled. Methylation is a detoxification pathway for selenium, and 

the extent of methylation is dose-dependent (Kobayashi et al. 2002). Monomethylated selenium is 

excreted as the major form in urine at deficient, normal, and low-toxic levels of selenium. When 

monomethylated selenium reaches a plateau in the urine (i.e., in the toxic dose range of selenium), 

trimethylated selenium in the urine and dimethylated selenium in the expired air increase. The major 

monomethylated form of selenium has been thought to be methyselenol, but Kobayashi et al. (2002) 

identified it as a selenosugar (1β-methylselenol-N-acetyl-D-galactosamine). 
SELENIUM 155 

3. HEALTH EFFECTS 

Humans accidentally exposed to high levels of selenium have been reported to have a noticeable garlic 

odor of the breath, probably as a result of excretion of dimethyl selenide in expired air (Bopp et al. 1982; 

Wilbur 1980). Garlic odor of the breath has been noted in humans following ingestion of toxic levels of 

sodium selenate (Civil and McDonald 1978) and following inhalation of elemental selenium dust or 

selenium dioxide (Glover 1970). 

In human populations with sufficient levels of selenium, dietary selenium is apparently partitioned into a 

selenite-exchangeable storage pool and a selenite-nonexchangeable storage pool. The seleniteexchangeable pool shows saturation kinetics. After this pool is filled, dietary selenium as selenomethionine may be the primary determinant of selenium bioavailability and serum selenium 

concentrations (Meltzer et al. 1990, 1992). There is experimental support for the concept that selenium 

metabolism can be divided into non-specific and specific components (Burk et al. 2001). 

Selenomethionine is the non-specific component as it appears to be incorporated into plasma proteins, 

presumably as selenomethionine, in proportion to its presence in the methionine pool. There is no 

indication that selenocysteine and inorganic selenium (selanate) were incorporated non-specifically into 

plasma protein, suggesting that these forms are metabolized by specific selenium metabolic processes. 

For example, selenocysteine seems to incorporate selenium into selenoproteins, but not into other proteins 

in place of cysteine (Burk et al. 2001). Selenate was either taken up directly by the liver or excreted in 

the urine, and selenite was taken up by red blood cells, reduced to selenide by glutathione, and then 

transported to the plasma and transferred to the liver (Suzuki and Ogra 2002). Data from both humans 

and Rhesus monkeys indicate that the selenium concentration in glutathione peroxidase is independent of 

the form of selenium administered and suggest a metabolic saturation at average intake rates (Butler et al. 

1990; Meltzer et al. 1990). 

In macaques that were orally administered doses of 0.025–0.3 mg selenium/kg as L-selenomethionine for 

up to 30 days, both erythrocyte selenium and glutathione peroxidase–specific activity showed a delay 

before increasing in a dose-related manner (Hawkes et al. 1992). At 0.15 and 0.3 mg selenium/kg, 

glutathione peroxidase-specific activity in erythrocytes continued to increase for 15 days after cessation 

of treatment and remained elevated through the end of the study (40 days after the end of treatment). The 

investigators attributed this effect to an initial deposition of selenium into a nonspecific pool (such as 

substitution for methionine in serum proteins), followed by slow release into the erythrocyte. Wistar rats 

also show incorporation of selenomethionine into proteins (Behne et al. 1991). 
SELENIUM 156 

3. HEALTH EFFECTS 

In rats, dimethyl selenide has been identified as the primary respiratory metabolite following injection of 

sodium selenite or sodium selenate (Hirooka and Galambos 1966b) and appears to be produced in the 

liver (Nakamuro et al. 1977). In mice, dimethyl selenide and dimethyldiselenide have been detected in 

expired air following the addition of unspecified amounts of sodium selenite, D,L-selenomethionine, or 

D,L-selenocystine to their drinking water (Jiang et al. 1983). A third unidentified volatile selenium 

compound was detected in expired air of the mice following D,L-selenomethionine injection (Jiang et al. 

1983). 

In rats, the trimethylselenonium ion has been identified as the predominant urinary metabolite following 

intraperitoneal administration of sodium selenite (Byard and Baumann 1967), sodium selenate, selenomethionine, selenocystine, or methylselenocysteine, or following ingestion of seleniferous wheat (Palmer 

et al. 1970). A total of 30.8% of the urinary selenium was in the form of trimethylselenonium after 

administration of 15 ppm selenium in wheat. Another major selenium metabolite that appeared in the 

urine more slowly than the trimethylselenonium ion was identified chromatographically, but the chemical 

structure of that metabolite was not defined (Palmer et al. 1970). 

Similarly, the trimethylselenonium ion was the major urinary metabolite of selenium excreted by rats 

after intraperitoneal injection of either methylselenocysteine (4 mg/kg) or selenocysteine (3 mg/kg) 

(Palmer et al. 1970). The amounts of trimethylselenonium ion excreted were 50.6 and 49.7% of the total 

urinary metabolites after methylselenocysteine and selenocysteine administration, respectively. In both 

cases, urinary metabolism accounted for only 10–15% of the administered dose. As selenium was not 

measured in feces or expired air, recovery of the dose was incomplete. In a review of the metabolic 

pathways resulting in the production of dimethyl selenide from selenite in rodents, Ganther (1979) 

indicated that reduction of selenite or selenate to dimethyl selenide requires glutathione and the 

methylating agent S-adenosylmethionine. NADPH, coenzyme A, ATP, and magnesium (II) salts are also 

required to provide optimal conditions for this reaction (Ganther 1979). Ganther (1971) and Hsieh and 

Ganther (1975) found that selenite initially reacts nonenzymatically with glutathione to form a selenotrisulfide derivative. The selenotrisulfide is then reduced nonenzymatically in the presence of glutathione 

or enzymatically by glutathione reductase in the presence of NADPH to a selenopersulfide (GSSeH). The 

selenopersulfide is unstable and decomposes to glutathione and selenium or is enzymatically reduced by 

glutathione reductase in the presence of NADPH to hydrogen selenide (Ganther 1971; Hsieh and Ganther 

1975). Hydrogen selenide can be methylated by S-adenosylmethionine in the presence of selenium 

methyltransferase to form dimethyl selenide (Figure 3-5). 
SELENIUM 157 

3. HEALTH EFFECTS 

Figure 3-5. Proposed Pathway for Formation of Dimethyl Selenide from 

Selenite in Animals* 
SELENIUM 158 

3. HEALTH EFFECTS 

Selenate apparently is not converted to dimethyl selenide as readily as is selenite. Studies of selenate 

metabolism are limited in mammals, but studies using bacteria indicate that selenate must be activated 

prior to conversion to selenite (Bopp et al. 1982). Dilworth and Bandurski (1977) demonstrated that in 

the presence of ATP, magnesium (II) salts, and ATP-sulfurylase, yeast could convert selenate to 

eventually yield selenite (Figure 3-6). Data regarding the metabolism of selenium sulfide after 

administration to humans or other animals were not located in the literature. 

3.4.4 Elimination and Excretion 

Excretion of selenium can occur in the urine, feces, and expired air (Griffiths et al. 1976; Hawkes et al. 

1992, 1994; Lathrop et al. 1972; McConnell and Roth 1966; Thomson and Stewart 1974). Sweat is a 

minor pathway of selenium excretion in humans (Levander et al. 1987). Moreover, the initial rate of 

excretion appears to be dose dependent (Lathrop et al. 1972; McConnell and Roth 1966; Thomson and 

Stewart 1974). Some researchers have found that urinary excretion and fecal excretion of selenium are 

similar, with each route contributing approximately 50% of the total output (Stewart et al. 1978). 

However, the proportion excreted via each route seems dependent on several factors, including the level 

of exposure, the time since exposure, and the level of exercise. Lactating women and subjects depleted of 

selenium have decreased excretion of selenium in the urine and feces (Martin et al. 1989a, 1989b; MoserVeillon et al. 1992). At high selenium exposure levels, excretion of selenium in expired air becomes 

more significant (McConnell and Roth 1966; Olson et al. 1963). 

3.4.4.1 Inhalation Exposure 

Following acute inhalation exposures to selenium compounds, humans excrete some of the absorbed dose 

in the expired air (Glover 1970), but no studies were located that actually quantified the rate of excretion 

or identified the selenium compounds in the expired air of humans. 

3.4.4.2 Oral Exposure 

Several human studies have indicated that the rate of urinary excretion is most rapid in the first 24 hours 

following oral administration or intravenous injection of sodium selenite (Kuikka and Nordman 1978; 
Selenate SeO4 Selenate

ATP

ATP sulfurylase

Mg++

PPi

“Activated Selenate” Adenosine-5’-selenolphosphate

GSH 

AMP 

GSH

AMP

GSSeO3

GSH 

GSSG 

GSH

GSSG

SeO3

*Adapted from Dilworth and Bandurski 1977 

SELENIUM 159 

3. HEALTH EFFECTS 

Figure 3-6. Activation and Reduction of Selenate to Selenite in 

Yeast Saccharomyces cerevisiae* 
SELENIUM 160 

3. HEALTH EFFECTS 

Thomson and Stewart 1974). Thomson and Stewart (1974) found that <6% of a trace dose (0.01 mg 

selenium) of orally administered sodium selenite was excreted in the urine within 24 hours of 

administration, whereas 64–73% of a 1-mg dose of selenium was excreted in the first 24 hours (Thomson 

1974). Thomson et al. (1977) also found that a lower proportion of the selenium from an oral dose of 

0.1 mg selenium administered as selenomethionine was excreted in the 24-hour urine than from a larger 

dose (1.0 mg selenium). Similarly, low selenium New Zealand residents excreted proportionally less 

selenium in their urine than North Americans of higher selenium status (Robinson et al. 1985), and there 

is limited evidence of such adaptation to selenium intake in some animal studies (Jaffe and Mondragon 

1969, 1975; WHO 1987). Thus, when higher amounts of selenium are administered, a higher proportion 

of the selenium is excreted in the urine during the first 24 hours following exposure. 

Decreasing urinary or fecal excretion appears to be the homeostatic mechanism by which the body retains 

greater amounts of selenium. Martin et al. (1989a) observed greater retention of selenium by individuals 

maintained on a selenium-deficient diet. This increase in retention was correlated with a decrease in fecal 

elimination. Similarly, the increased retention of selenium from selenomethionine compared to selenite 

was correlated with decreased elimination (Swanson et al. 1991). Lactating women have a greater 

retention of selenium from selenomethionine compared to selenite and a decreased urinary elimination 

(Moser-Veillon et al. 1992). Muscle activity seems to influence urinary excretion of selenium as 

demonstrated by the doubling of selenium concentration in the urine of women following vigorous 

exercise (Oster and Prellwitz 1990). 

Less information is available regarding the elimination of selenium in the feces of humans than in the 

urine of humans. However, levels of fecal excretion of selenium have been reported to be similar to 

levels of urinary selenium excretion when dietary levels of selenium are not excessive (Patterson et al. 

1989). Over a 14-day period, Stewart et al. (1978) found urinary elimination of selenium to average 

0.013 mg selenium/day and fecal elimination of selenium to average 0.011 mg selenium/day in four New 

Zealand women exposed to 0.024 mg selenium/day in their normal diets. Balance data on 27 healthy U.S. 

adults (12 men and 15 women) similarly indicated an approximately even split between urine and fecal 

selenium excretion (Levander and Morris 1985). Determination of selenium balance at four time points 

(spring, summer, fall, and winter) showed respective average levels of selenium in the urine and feces of 

48±2 and 34±1 μg/day in the men, and 39±1 and 23±1 μg/day in the women. Plasma selenium levels 

remained essentially constant during the year and were similar in the men and women, averaging 136±4 

and 133±4 ng/L, respectively. Although the U.S. men consumed more selenium in the diet than the 
SELENIUM 161 

3. HEALTH EFFECTS 

women, their selenium balance (8±4) was less positive than the women (12±3) because they tended to 

excrete more in the feces (Levander and Morris 1985). It has been suggested that some of the selenium 

content in feces can be attributed to biliary excretion (Levander and Baumann 1966a, 1966b). 

In humans, whole body retention studies following oral administration of sodium selenite have indicated 

that selenium elimination is triphasic (Thomson and Stewart 1974). During the initial phase, which lasted 

about 1 week, elimination of selenium was rapid, with a half-life of approximately 1 day (Thomson and 

Stewart 1974). In the second phase, which also lasted approximately 1 week, selenium elimination was 

slower, with a half-life of 8–9 days. In the third phase, selenium elimination was much slower, with a 

half-life estimated to be 115–116 days. The first two elimination phases correspond to the fecal 

elimination of nonabsorbed selenium and the urinary excretion of absorbed but unutilized selenium 

(Thomson and Stewart 1974). Selenomethionine elimination is also triphasic; however, its terminal halflife is longer than that of sodium selenite. The average half-lives of selenomethionine for the three phases 

were measured to be approximately 0.4–2, 5–19, and 207–290 days, respectively (Griffiths et al. 1976). 

An examination of elimination data from 44 pigs exposed to excess selenium as sodium selenite in feed 

was found to fit a one-compartment model of selenium elimination (Davidson-York et al. 1999). Serum 

selenium levels were monitored over a period of 46 days beginning 1–14 days after termination of 

exposure to the feed containing excess selenium. Data were not adequate to depict the initial distribution 

phase, but a geometric mean elimination half-life of 12 days was calculated. It is likely that the period of 

elimination included in this study corresponds to the second phase described by Thomson and Stewart 

(1974). 

The chemical form of selenium may play a role in determining how rapidly selenium is excreted in the 

urine. In rats, the rate of urinary excretion of selenium has been found to be greater following oral 

administration of sodium selenite than of selenomethionine (Thomson and Stewart 1973). A comparison 

of excretion of selenium by selenium-depleted rats after oral administration of sodium selenate, 

selenomethionine, or methyl selenocysteine (from high-selenium broccoli) found that excretion of 

selenium from methyl selenocysteine or selenomethionine was significantly lower than from sodium 

selenate; further, that there was no significant difference between secretion of selenium from methyl 

selenocysteine and selenomethionine (Finley 1998). This may contribute to the greater retention of 

selenium from selenomethionine, than from inorganic selenium (Martin et al. 1989a). However, another 

study of excretion of selenium from rats fed selenium as either sodium selenite or selenomethionine found 

that excretion of selenium increased with administered dose, but was similar for both forms of selenium 

(Shiobara et al. 1998). 
SELENIUM 162 

3. HEALTH EFFECTS 

As exposure to oral L-selenomethionine increased in macaques, the amount of selenium eliminated in the 

urine/day increased, as did the maximum rate of urinary excretion. However, the percentage of 

administered dose appearing in the urine decreased with an increase in dose (Hawkes et al. 1994). 

3.4.4.3 Dermal Exposure 

No studies were located regarding the excretion of selenium by humans or other animals after dermal 

exposure to elemental selenium or selenium compounds. 

3.4.4.4 Other Routes of Exposure 

Whole body retention studies in sheep following injection of selenium have indicated that selenium 

excretion in animals follows a triexponential profile (Blodgett and Bevill 1987b; Ewan et al. 1967). In a 

2-week study, Blincoe (1960) estimated the half-life for 75Se in rats following intraperitoneal injection of 

75Se-labeled sodium selenite (0.93 mg selenium/kg). Initially, the excretion of selenium was rapid, with a 

half-life of approximately 0.8 day; the second phase of excretion was slower, with a half-life of 13 days. 

These results parallel the initial phases of selenium excretion seen in humans. The abbreviated duration 

of the Blincoe (1960) study did not permit the determination of a terminal elimination phase half-life. In 

rats, Ewan et al. (1967) found the final phase of elimination of selenium following a single subcutaneous 

injection of sodium selenite to be dose independent (from 0.008 mg selenium/kg to 2 mg selenium/kg), 

with a half-life of 65–78 days. Blodgett and Bevill (1987b) found the elimination rate of selenium in 

sheep during the second phase following a single intramuscular injection of sodium selenite to be dose 

dependent, with larger doses resulting in longer half-lives (i.e., doses of 0.4, 0.6, 0.7, or 0.8 mg 

selenium/kg resulting in half-lives for selenium elimination of 6.3, 8.8, 15.1, and 20.4 hours, 

respectively). The reasons for the decreasing elimination rate with increasing dose during the second 

phase are not clear. 

Dietary levels of selenium and the individual's selenium nutritional status are the most important factors 

that influence the route and rate of selenium excretion. Selenium excretion in expired air is only 

significant when exposures to selenium are high. Rats injected subcutaneously with sodium selenite at 

doses of 2.2–5.4 mg selenium/kg excreted 41–62% of the administered selenium in exhaled air, whereas 

rats injected with sodium selenite at doses of 0.005–0.9 mg selenium/kg excreted only 0.2–11% of the 
SELENIUM 163 

3. HEALTH EFFECTS 

administered selenium in expired air (McConnell and Roth 1966; Olson et al. 1963). As the amount of 

administered sodium selenite increased, the percent of the administered selenium excreted in the urine 

decreased (from approximately 22–33% of the administered selenium at doses of 0.005–0.9 mg 

selenium/kg to 3–14% of the administered selenium at doses of 3.1–5.4 mg selenium/kg) (McConnell and 

Roth 1966). Selenium in the feces was not measured in this study. Burk et al. (1972) found that as the 

dietary level of sodium selenite was increased, a larger proportion of an injected tracer dose of selenium 

(as sodium selenite) was excreted. At a dietary level of 0.005 mg selenium/kg, approximately 60% of the 

injected selenium had been excreted in the first 35 days following administration. At a dietary level of 

0.05 mg selenium/kg, over 94% of the injected selenium had been excreted over the same period of time. 

In experimental animals, other factors that can cause an increase in selenium levels in expired air are 

higher dietary levels of selenium, protein, or methionine (Ganther et al. 1966). Phenobarbital induction of 

microsomal enzymes has also led to increased exhalation of selenium following intravenous 

administration of sodium selenite (Sternberg et al. 1968). 

3.4.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models 

Physiologically based pharmacokinetic (PBPK) models use mathematical descriptions of the uptake and 

disposition of chemical substances to quantitatively describe the relationships among critical biological 

processes (Krishnan et al. 1994). PBPK models are also called biologically based tissue dosimetry 

models. PBPK models are increasingly used in risk assessments, primarily to predict the concentration of 

potentially toxic moieties of a chemical that will be delivered to any given target tissue following various 

combinations of route, dose level, and test species (Clewell and Andersen 1985). Physiologically based 

pharmacodynamic (PBPD) models use mathematical descriptions of the dose-response function to 

quantitatively describe the relationship between target tissue dose and toxic end points. 

PBPK/PD models refine our understanding of complex quantitative dose behaviors by helping to 

delineate and characterize the relationships between: (1) the external/exposure concentration and target 

tissue dose of the toxic moiety, and (2) the target tissue dose and observed responses (Andersen et al. 

1987; Andersen and Krishnan 1994). These models are biologically and mechanistically based and can 

be used to extrapolate the pharmacokinetic behavior of chemical substances from high to low dose, from 

route to route, between species, and between subpopulations within a species. The biological basis of 
SELENIUM 164 

3. HEALTH EFFECTS 

PBPK models results in more meaningful extrapolations than those generated with the more conventional 

use of uncertainty factors. 

The PBPK model for a chemical substance is developed in four interconnected steps: (1) model 

representation, (2) model parametrization, (3) model simulation, and (4) model validation (Krishnan and 

Andersen 1994). In the early 1990s, validated PBPK models were developed for a number of 

toxicologically important chemical substances, both volatile and nonvolatile (Krishnan and Andersen 

1994; Leung 1993). PBPK models for a particular substance require estimates of the chemical substancespecific physicochemical parameters, and species-specific physiological and biological parameters. The 

numerical estimates of these model parameters are incorporated within a set of differential and algebraic 

equations that describe the pharmacokinetic processes. Solving these differential and algebraic equations 

provides the predictions of tissue dose. Computers then provide process simulations based on these 

solutions. 

The structure and mathematical expressions used in PBPK models significantly simplify the true 

complexities of biological systems. If the uptake and disposition of the chemical substance(s) is 

adequately described, however, this simplification is desirable because data are often unavailable for 

many biological processes. A simplified scheme reduces the magnitude of cumulative uncertainty. The 

adequacy of the model is, therefore, of great importance, and model validation is essential to the use of 

PBPK models in risk assessment. 

PBPK models improve the pharmacokinetic extrapolations used in risk assessments that identify the 

maximal (i.e., the safe) levels for human exposure to chemical substances (Andersen and Krishnan 1994). 

PBPK models provide a scientifically sound means to predict the target tissue dose of chemicals in 

humans who are exposed to environmental levels (for example, levels that might occur at hazardous waste 

sites) based on the results of studies where doses were higher or were administered in different species. 

Figure 3-7 shows a conceptualized representation of a PBPK model. 

Two models for selenium were located in the literature. Patterson and coworkers (Patterson and Zech 

1992; Patterson et al. 1989, 1993) have developed compartmental models of the kinetics of selenium 

orally administered as selenite or selenomethionine in adult humans. 
SELENIUM 165 

3. HEALTH EFFECTS 

Figure 3-7. Conceptual Representation of a Physiologically Based 

Pharmacokinetic (PBPK) Model for a Hypothetical Chemical Substance 

Source: adapted from Krishnan et al. 1994 

Note: This is a conceptual representation of a physiologically based pharmacokinetic (PBPK) model for a 

hypothetical chemical substance. The chemical substance is shown to be absorbed via the skin, by 

inhalation, or by ingestion, metabolized in the liver, and excreted in the urine or by exhalation. 
SELENIUM 166 

3. HEALTH EFFECTS 

Patterson et al. (1989) Selenite Model 

Description of the model. Patterson and coworkers (Patterson and Zech 1992; Patterson et al. 

1989, 1993) developed a compartmental model of the kinetics of ingested selenite in adult humans based 

on data from human subjects who consumed a single oral dose of 200 μg 74Se as selenite. The model 

assumes that 84% of the administered selenium is absorbed and that absorption is rapid. Absorbed 

selenite is assumed to distribute to six compartments: gastrointestinal tract, plasma, hepatopancreatic/ 

lymphatic system, liver/pancreas, bile, and tissues (Figure 3-8). Unabsorbed selenium is excreted in the 

feces. Absorption occurs from the gastrointestinal compartment (probably the small intestine, but also 

possibly the stomach) into a rapidly turning-over pool (the intestinal cells or enterocytes) from which it 

leaves by two pathways. The central compartment is represented as four kinetically distinct plasma pools, 

P1 (the portal circulation), P2 (before passage through the liver), P3 (after passage through the liver), and 

P4 (after passage through the tissues). In the first pathway, selenium enters P1. The second pathway is to 

a liver/pancreatic compartment. Transport into and out of P1 is very rapid (T1/2 approximately 

0.36 hours) and this may represent selenium in the portal circulation passing through the liver before 

appearing in P3, but not removed in the first pass. The second pathway is via the hepatopancreatic/ 

lymphatic system compartment to a second plasma pool (P2). Appearance of selenium in P2 is delayed 

(T1/2 approximately 0.55 hours), representing the time needed to move through the hepatopancreatic/ 

lymphatic system compartment. From the two plasma pools (P1 and P2), selenium can be excreted in the 

urine (T1/2 approximately 3.94 and 1.96 hours, respectively) or it can move into the liver/pancreas 

compartment. After a delay of 4–6 hours, the selenium leaves the liver/pancreas either to a bile 

compartment (T1/2 approximately 0.13 hours) and thence to the gut (G1) for excretion in feces or to a third 

plasma pool (P3) (T1/2 approximately 0.19 hours). From P3, selenium can be excreted in the urine (T1/2 

approximately 4.15 hours) or can move into a large, slowly turning-over tissue compartment. Finally, 

selenium is transferred very slowly (T1/2 approximately 1.27 hours) from the tissues (probably final 

metabolic products) to a fourth plasma pool (P4) and hence to the urine (T1/2 approximately 6.54 hours). 

Validation of the model. The extent to which this model has been validated is not described in 

Patterson and coworkers (Patterson and Zech 1992; Patterson et al. 1991, 1993). 

Risk assessment. The model was designed to simulate the pharmacokinetics of selenium orally 

administered as selenite to humans as a preparation for a larger anticancer supplementation study jointly 

undertaken by the National Cancer Institute (NCI) and the U.S. Department of Agriculture (USDA) 

(Patterson and Zech 1992; Patterson et al. 1991, 1993). 
SELENIUM 167 

3. HEALTH EFFECTS 

Figure 3-8. Selenite Model, a Kinetic Model for Selenite Metabolism 

INITIAL DOSE INITIAL DOSE *

GASTRO-INTESTINAL TRACT 

G1 G2 G3 

ENT 

LI 

LIVER/

PANCREAS TISSUES 

T2 BILE 

T1 L/P

P4 P3 P1 

HPL 

P2 

URINE 

FECES 

GASTRO-INTESTINAL TRACT

G1 G2 G3

ENT

LI

LIVER/

PANCREAS TISSUES

T2 BILE

T1 L/P

P4 P3 P1

HPL

P2

URINE

FECES

The arrow with an asterisk indicates the site of entry of the oral Se tracer. Arrows between compartments 

represent pathways of fractional transport. Compartments depicted as rectangles represent delays. 

Compartments G1, G2, G3, three-gut compartments, probably the small intestine; ENT, enterocytes 

(intestinal cells); HPL, compartment in hepato-pancreatic subsystem or lymphatic system; L/P, liver and 

pancreas; LI, large intestine; T1, T2, peripheral tissues, e.g., skeletal muscle, bone, kidney. Feces and 

urine compartments are drawn in the shape of test tubes to represent fractional (single) collections. The 

model includes absorption distributed along the gastrointestinal tract, enterohepatic recirculation, 

four-kinetically distinct plasma pools, P1–P4, a subsystem consisting of liver and pancreas, and a slowly 

turning-over tissue pool. 

Source: Patterson et al. 1993 
SELENIUM 168 

3. HEALTH EFFECTS 

Target tissues. The model is designed to simultaneously account for the appearance and 

disappearance of selenium in plasma, urine, and feces after administration of a single oral dose of 74Se as 

selenite (Patterson and Zech 1992; Patterson et al. 1991, 1993). 

Species extrapolation. The model is designed for applications to human dosimetry and cannot be 

applied to other species without modification. 

Interroute extrapolation. The model is designed to simulate oral exposures to selenite and cannot 

be applied to other routes of exposure without modification. 

Extrapolation to other forms of selenium. The model is designed to simulate oral exposures to 

selenite and cannot be applied to other forms of selenium without modification. 

Swanson et al. (1991) Selenomethionine Model 

Description of the model. Swanson and coworkers (Patterson et al. 1993; Swanson et al. 1991) 

produced a model for ingested selenomethionine in adult humans based on data from human subjects who 

consumed a single oral dose of 200 μg 74Se as selenomethionine and the model of the kinetics of ingested 

selenite described above. Four major changes (indicated by bold lines in Figure 3-9) were made to the 

selenite model to achieve an adequate fit to the selenomethionine data: (1) the amount of label absorbed 

into the enterocyte was increased (the absorption of 74Se was 98% for selenomethionine compared with 

84% for selenite), (2) the amount of label removed from the plasma in the first pass through the liver was 

increased, (3) a pathway from P4 back to the liver was added, providing for conservation and reutilization 

of amino acids (estimated 95% of material from P4 is recycled), and (4) a second tissue subgroup was 

added to the model and rate constants were adjusted so that the subgroups had different turnover times. 

The most important differences between the selenite and selenomethionine models lie in the turnover 

times. The estimated turnover times in the plasma, liver/pancreas, and tissues are shorter for selenomethionine than for selenite, but the estimated turnover time for the whole body is more than twice as 

long for selenomethionine as for selenite. This is probably because selenite is not recirculated, whereas 

selenomethionine is extensively recycled, passing through the individual organs and tissues many times 

before being excreted. 
SELENIUM 169 

3. HEALTH EFFECTS 

Figure 3-9. Selenomethionine Model, a Kinetic Model for 

Selenomethionine Metabolism 

* INITIAL DOSE 

GASTRO-INTESTINAL TRACT 

GI G2 G3 

ENT 

L1 

LIVER/

PANCREAS TISSUES A 

T2 BILE 

T1 L/P 

P4 P3 P1 

HPL 

P2 

URINE 

TISSUES B 

T3 

T4 

FECES 

The arrow with an asterisk indicates the site of the oral Se tracer. Arrows between compartments 

represent pathways of fractional transport. Compartments depicted as rectangles represent delays. G1, 

G2, G3, three-gut compartments, probably small intestine; ENT, enterocytes (intestinal cells); HPL, 

compartment in hepatopancreatic subsystems or lymphatic system; L/P, liver and pancreas; LI, large 

intestine; T1, T2, T3, T4, peripheral tissues, e.g., skeletal muscle, bone, kidney. Feces and urine along 

the gastrointestinal tract, enterohepatic recirculation, four-kinetically distinct plasma pools, P1–P4, a 

subsystem consisting of the liver and pancreas, two tissue subsystems that are slowly turning-over, and a 

pathway for reutilization of selenium metabolites from peripheral tissues. The bold lines indicate the 

major modifications to the Selenite Model (Figure 3-8). 

Source: Patterson et al. 1993 
SELENIUM 170 

3. HEALTH EFFECTS 

Validation of the model. The extent to which this model has been validated is not described by the 

authors (Patterson et al. 1993; Swanson et al. 1991). 

Risk assessment. The model was designed to simulate the pharmacokinetics of selenium orally 

administered as selenomethionine to humans as a preparation for a larger anti-cancer supplementation 

study jointly undertaken by the NCI and the USDA (Patterson et al. 1993; Swanson et al. 1991). 

Target tissues. The model is designed to simultaneously account for the appearance and 

disappearance of selenium in plasma, urine, and feces after administration of a single oral dose of 74Se as 

selenomethionine (Patterson et al. 1993; Swanson et al. 1991). 

Species extrapolation. The model is designed for applications to human dosimetry and cannot be 

applied to other species without modification. 

Interroute extrapolation. The model is designed to simulate oral exposures to selenomethionine 

and cannot be applied to other routes of exposure without modification. 

Extrapolation to other forms of selenium. The model is designed to simulate oral exposures to 

selenomethionine and cannot be applied to other forms of selenium without modification. 

3.5 MECHANISMS OF ACTION 

3.5.1 Pharmacokinetic Mechanisms 

As discussed in Section 3.4.1, selenium is readily absorbed by inhalation or ingestion when present in any 

of several compounds. Inhalation and oral absorption are extensive, although the rate of absorption varies 

depending on the form of selenium (Medinsky et al. 1981a; Moser-Veillon et al. 1992; Swanson et al. 

1991; Weissman et al. 1983; Young et al. 1982). Oral bioavailability is generally independent of the 

exposure level, but may be increased in some selenium-deficient individuals (Griffiths et al. 1976; Martin 

et al. 1989a; Thomson 1974; Thomson et al. 1977). Selenate and selenomethionine appear to be absorbed 

by the intestine largely unchanged, while selenite and selenocysteine are metabolized during absorption 

(Hasegawa et al. 1995, 1996b; Spencer and Blau 1962; Whanger et al. 1976, 1996). No evidence of 

significant dermal absorption of selenium by humans was located, although mice can absorb topicallyapplied selenomethionine (Burke et al. 1992b). An active transport mechanism for selenomethionine 
SELENIUM 171 

3. HEALTH EFFECTS 

absorption in the intestine has been described (Spencer and Blau 1962), but mechanisms of absorption 

and distribution for dermal and pulmonary uptake are unknown and subject to speculation. 

Absorbed selenium is carried throughout the body in the blood, eventually being distributed to all tissues. 

Injection studies in humans have shown that after selenium enters the blood, it rapidly becomes proteinbound (Burk 1974; Hirooka and Galambos 1966a), while in vitro studies have shown that selenite is 

accumulated in erythrocytes via an active transport mechanism (Lee et al. 1969). Selenium is an essential 

element and is incorporated into selenoproteins (e.g., glutathione peroxidase, iodothyronine deiodinases) 

as selenocysteine. Most studies report similar distribution patterns for selenium, regardless of the form in 

which it was administered; however, the concentration reached is generally higher for doses delivered as 

an organic form of selenium, such as selenomethionine, than for the same dose delivered as an inorganic 

form (Behne et al. 1991; Butler et al. 1990; Grønbaek and Thorlacius-Ussing 1992; Ip and Hayes 1989; 

Salbe and Levander 1990b; Shiobara et al. 1998; Zi-Jian Jie 1992). In humans, the highest levels of 

selenium are found in the liver and kidney (see Table 3-6 for normal levels of selenium in human tissues). 

Selenomethionine is not synthesized by humans, but can be incorporated into proteins in the place of 

methionine; because of this, selenomethionine is retained for a longer time within the body than inorganic 

forms, and it may therefore represent a storage form of the element. Unlike selenomethionine, there is no 

evidence that selenocysteine and inorganic selenium (selanate) are incorporated non-specifically into 

plasma protein, suggesting that these forms are metabolized by specific selenium metabolic processes. 

For example, selenocysteine seems to incorporate selenium into selenoproteins, but not into other proteins 

in place of cysteine (Burk et al. 2001). 

Selenium and the glutathione (GSH) system have key functions in the body’s antioxidant defense (Arteel 

and Sies 2001; Brigelius-Flohe 1999). GSH is involved in direct interception of pro-oxidants, as well as 

the reduction of other antioxidants from their oxidized forms (Arteel and Sies 2001). GSH also has 

ancillary functions (e.g., metabolism, cell signaling, and protein interactions) that can mediate defense 

against antioxidants. The redox reactions of GSH involve glutathione peroxidase (GPX) and glutathione 

disulfide (GSSG) as catalysts, whereas the main class of enzymes involved in thioether formation are the 

GSH transferases. Antioxidant protection by selenium in the mammalian cell is mediated by selenoamino 

acids, either as selenocysteine or selenomethionine. Selenomethionine has GPX-like activity, and the 

active site of GPX contains selenocysteine residues. GPX catalyzes the reduction of various kinds of 

hydroperoxides (e.g., simple hydroperoxides, lipid peroxides) by using GSH as the reducing substrate. 

Several isozymes of GPX have been identified, including plasma GPX, gastrointestinal GPX, and 

phospholipid hydroperoxide GPX (reduces lipid hydroperoxides found in biomembranes and sperm) 
SELENIUM 172 

3. HEALTH EFFECTS 

(Brigelius-Flohe 1999). Other selenoproteins (e.g., selenoprotein P and thioredoxin reductase) also have 

been shown to have antioxidant properties, and can function in the defense against peroxynitrite, by 

reducing this oxidizing and nitrating species into nitrite (Arteel and Sies 2001; Holmgren and Kumar 

1989; Burke and Hill 2000; Ganther 1999). 

The antioxidant action of GPX towards hydroperoxides appears to involve an enzymatic catalysis reaction 

cycle (a ‘tert-uni ping-pong’ mechanism) (Arteel and Sies 2001). The reaction cycle is thought to 

proceed in three main steps, involving the enzyme-bound selenocysteine, which is present as the selenol. 

In the first step of the reaction, the organic hydroperoxide reacts to yield selenenic acid and the 

corresponding alcohol. The remaining steps consist of the sequential reduction by thiols (GSH), leading 

to regeneration of the selenol and glutathione disulfide. GPX serves more as an ancillary reductant than 

as a direct antioxidant per se. 

Deiodination is an important mechanism for the deactivation of the thyroid hormones, T4 and T3 , as well 

as for the production of extrathyroidal thyroid T3. The deiodination reactions are catalyzed by seleniumdependent deiodinase enzymes (selenodeiodinases). Three selenodeiodinases have been described that 

differ in substrate preference, reaction products, response to inhibitors, and response to T3 (Larsen et al. 

1998). Full activity of each enzyme requires selenocysteine in the amino acid sequence of the active site, 

which is the basis for deiodination activity being responsive to nutritional selenium status (see 

Section 3.9). 

Excretion of selenium by humans occurs in the urine, feces, expired air, and sweat, but urine and feces are 

the major routes of elimination. Some of the selenium in feces may be due to bilary excretion (Levander 

and Baumann 1966a, 1966b). Elimination is reduced in selenium-deficient individuals and may represent 

a mechanism by which selenium levels are regulated (Martin et al. 1989a; Swanson et al. 1991). 

Methylation is an important mechanism of detoxification for selenium; dimethyl selenide is exhaled, and 

the trimethylselenonium ion is the major urinary metabolite of selenium. Experiments in mice suggest 

that the hepatic toxicity of selenium may be at least partly due to depression of selenium methylation in 

the liver, resulting in the accumulation of excess selenides (Nakamuro et al. 2000). 

3.5.2 Mechanisms of Toxicity 

Selenium in the body can be grouped in three main categories: selenium in proteins, non-protein 

selenium species, and selenoamino acids (Lobinski et al. 2000). The most prevalent selenium species 
SELENIUM 173 

3. HEALTH EFFECTS 

include selenocysteine, selenomethionine, and inorganic forms of selenium (selenite and selenate). 

Selenocysteine-containing proteins are particularly important because they are largely responsible for the 

antioxidant properties of selenium. The main selenoproteins are glutathione peroxidase (GPX), 

thioredoxin reductase, and iodothyronine 5'-deiodinases, and the activity of these selenocysteine enzymes 

generally decreases and increases when selenium is depleted or repleted (Lobinski et al. 2000). Selenium 

can also be incorporated directly into non-specific proteins in the place of methionine (i.e., as 

selenomethionine), which contributes to the pool of selenomethionine-rich proteins present in human and 

animal tissues, or become part of selenium-binding proteins in which selenium is not covalently bound to 

the molecules (Arteel and Sies 2001; Bansal et al., 1989, 1990; Gladyshev and Kryukov 2001; Lobinski et 

al. 2000; Sani et al., 1988). 

Little is known about the specific biochemical mechanism(s) by which selenium and selenium 

compounds exert their acute toxic effects. Generally, water-soluble forms are more easily absorbed and 

are generally of greater acute toxicity. Several mechanisms have been proposed to explain the various 

long-term toxic effects of excess selenium, such as alterations in the hair, skin, nails, liver, thyroid, and 

nervous system, as discussed below. This includes information on mechanisms by which selenium exerts 

effects as a component of GPX, thioredoxin reductase, and the iodothyronine deiodinases, although the 

roles of other selenium-containing proteins in mammalian metabolism have not been clarified. Selenium 

also has strong interactions with other nutrients such as vitamin E, toxic metals such as mercury and 

cadmium, and various xenobiotics (see Section 3.9). 

Selenium readily substitutes for sulfur in biomolecules and in many biochemical reactions, especially 

when the concentration of selenium is high and the concentration of sulfur is low in the organism 

Stadtman 1983; Raisbeck 2000). Inactivation of the sulfhydryl enzymes necessary for oxidative reactions 

in cellular respiration, through effects on mitochondrial and microsomal electron transport, might 

contribute to acute selenium toxicity (Levander 1982; Lombeck et al. 1987; Mack 1990; Shamberger 

1981). Selenium may have a role in hepatic heme metabolism that is related to GPX or lipid peroxidation 

(Levander 1982). Selenocysteine is specifically found in some proteins (e.g., glutathione peroxidase); 

selenomethionine appears to randomly substitute for methionine in protein synthesis. This appears to be 

an additional mechanism for intermediate- or chronic-duration toxicity (Levander 1982; Stadtman 1983; 

Tarantal et al. 1991). Skin, hair, and nail damage are significant indicators of chronic selenium 

overexposure. The mechanism causing these integumentary effects is unclear, but could be related to the 

high selenium concentrations in these tissues as a consequence of the substitution of selenium for sulfur 

in certain amino acids, including the disulfide bridges that provide tertiary structure and function to 
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proteins. For example, substitution of selenium for sulfur in keratin results in weakened physical protein 

structure and failure of keratinized tissues such as hair and hoof (Raisbeck 2000). The nails and hair are 

considered to be routes for excretion of excess selenium (Yang et al. 1989b). 

Considerable evidence is available supporting oxidative stress as the key biochemical lesion of selenium 

intoxication (Raisbeck 2000; Spallholz et al. 1994). Inorganic forms of selenium appear to react with 

tissue thiols by redox catalysis resulting in formation of reactive oxygen species (superoxide anion [O2

-

]). 

For example, selenite is a prooxidant catalyst that reacts with GSH endogenously in cells or 

extracellularly causes toxicity by the formation of superoxide and elemental selenium (Seko and Imura 

1997; Seko et al. 1989; Spallholz 1994). Selenocystamine (a diselenide) catalyzes the formation of 

superoxide under aerobic conditions in the presence of thiol; this reaction could play a role in the toxicity 

of diselenides and alkylselenols (Chaudiere et al. 1992). Selenium can have inhibitory effects on thiol 

proteins by modification via (1) formation of S-Se-S (selenotrisulfides) and S-Se (selenylsulfide) bonds, 

(2) catalysis of S-S (disulfide bonds) with no incorporation of selenium in the protein, and (3) formation 

of Se-Se diselenides (Ganther 1999). Proteins that contain regulatory cysteines can similarly form 

selenium adducts with toxicity resulting from inactivation of essential thiol groups. 

Selenium can also play a role in the redox-regulating activities of GPXs with inflammatory superoxides 

and phospholipid hydroperoxides. A selenoprotein P-supported plasma GPX could bind to endothelial 

cells and protect them against inflammatory hydroperoxides (Hill and Burke 1989, 1997). Metabolites 

from reactions of GPX and phospholipid hydroperoxides could suppress cytokine or growth factor 

triggered gene activation (Flohe et al. 1997). Selenium appears to be a key element that, through its 

modulation of GPX activity, can inhibit activation of the transcription factor NF-κB, which is involved in 

the regulation of the expression of numerous cellular genes, particularly those involved in immune, 

inflammatory, and stress responses (Kretz-Remy and Arrigo 2001). 

Apotosis induced by tumor necrosis factor might be inhibited by overexpression of cytosolic GPX or 

phospholipid hydroperoxide GPX because the apoptotic signaling cascade could be stimulated by 

hydroperoxides (Brigelius-Flohe 1999). Selenium compounds that form the methylselenide anion 

(selenol) have been shown to induce cellular apotosis, and one selenium compound, seleniummethylselenocysteine, induced apotosis in cancer cells through activation of capsases (a likely mechanism 

for other selenium compounds that also induce apotosis) (Ganther 1999; Spallholz 2001). Hypotheses for 

the protective role of selenium against cancer development include the inhibition of carcinogen-induced 

covelant DNA adduct formation, retardation of oxidative damage to DNA, lipids, and proteins, and 
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modulation of cellular and molecular events that are critical in cell growth inhibition and in the multi-step 

carcinogenesis process (El-Baoumy 2001; Ganther 1999; Spallholz 2001). 

Intracellular redox function can also be affected by selenium deficiency. In general, the toxicity of 

compounds that are metabolized to form free radicals increases in selenium-deficient animals, and many 

of the effects are prevented by supplements of selenium. For example, the active role of selenium in 

thioredoxin reductase helps reduce nucleotides in DNA synthesis, and selenium in GPX reduces 

phospholipid hydroperoxides and hydrogen peroxide (Ganther 1999; Holmgren and Kumar 1989; 

Spallholz 2001). Peroxidative degradation of polyunsaturated fatty acids in membranes causes formation 

of chemicals, such as free radicals, aldehydes, and epoxides, which can have cytotoxic, hepatotoxic, and 

genotoxic effects (Esterbauer et al. 1989). The role of selenium in protecting against early pregnancy loss 

may be linked to reduced antioxidant protection of biological membranes and DNA by low concentrations 

of GPX. Levels of hemoglobin adducts from aldehydes and epoxides in selenium-deficient animals were 

enhanced due to loss of selenium-dependent GPX activity (Kautiainen et al. 2000). Degenerative diseases 

such as skeletal and cardiac myopathies, which occur particularly in selenium-deficient cattle and sheep, 

appear to be due to loss of membrane phospholipid hydroperoxide GPX activity (Arthur and Beckett 

1994b). 

Selenium status can also influence thyroid hormone function via the deiodinase enzymes (Brätter and 

Negretti De Brätter 1996; Hawkes and Turek 2001). Selenium is a critical component of the deiodinase 

enzymes, including iodothyronine 5'-deiodinases, which convert the prohormone thyroxine (T4) to the 

active circulating form, triiodothyronine (T3) (Delange 2000; Köhrle 1994; St Germain and Galton 1997). 

Selenium is also a component of GPX, the main enzyme responsible for protecting thyroid cells against 

oxidative damage. GPX is involved in the detoxification of hydrogen peroxide, which is produced in the 

thyroid during the conversion of T4 to T3. 

3.5.3 Animal-to-Human Extrapolations 

No studies were located that specifically examined species-related differences in selenium 

pharmacokinetics. Similar patterns of absorption, distribution, and elimination have been reported for 

human and animal systems and the dermal, endocrine, and neurological effects of chronic exposure in 

humans are similar to those reported for animals exposed to very high doses of selenium. However, 

species-specific differences in toxicity are present (e.g., the main effect of selenium toxicity in rodents is 
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damage to the liver, which is not observed in humans) and this may represent evidence of underlying 

differences in how selenium is metabolized. 

3.6 TOXICITIES MEDIATED THROUGH THE NEUROENDOCRINE AXIS 

Recently, attention has focused on the potential hazardous effects of certain chemicals on the endocrine 

system because of the ability of these chemicals to mimic or block endogenous hormones. Chemicals 

with this type of activity are most commonly referred to as endocrine disruptors. However, appropriate 

terminology to describe such effects remains controversial. The terminology endocrine disruptors, 

initially used by Colborn and Clement (1992), was also used in 1996 when Congress mandated the 

Environmental Protection Agency (EPA) to develop a screening program for “...certain substances 

[which] may have an effect produced by a naturally occurring estrogen, or other such endocrine 

effect[s]...”. To meet this mandate, EPA convened a panel called the Endocrine Disruptors Screening and 

Testing Advisory Committee (EDSTAC), which in 1998 completed its deliberations and made 

recommendations to EPA concerning endocrine disruptors. In 1999, the National Academy of Sciences 

released a report that referred to these same types of chemicals as hormonally active agents. The 

terminology endocrine modulators has also been used to convey the fact that effects caused by such 

chemicals may not necessarily be adverse. Many scientists agree that chemicals with the ability to disrupt 

or modulate the endocrine system are a potential threat to the health of humans, aquatic animals, and 

wildlife. However, others think that endocrine-active chemicals do not pose a significant health risk, 

particularly in view of the fact that hormone mimics exist in the natural environment. Examples of 

natural hormone mimics are the isoflavinoid phytoestrogens (Adlercreutz 1995; Livingston 1978; Mayr et 

al. 1992). These chemicals are derived from plants and are similar in structure and action to endogenous 

estrogen. Although the public health significance and descriptive terminology of substances capable of 

affecting the endocrine system remains controversial, scientists agree that these chemicals may affect the 

synthesis, secretion, transport, binding, action, or elimination of natural hormones in the body responsible 

for maintaining homeostasis, reproduction, development, and/or behavior (EPA 1997). Stated differently, 

such compounds may cause toxicities that are mediated through the neuroendocrine axis. As a result, 

these chemicals may play a role in altering, for example, metabolic, sexual, immune, and neurobehavioral 

function. Such chemicals are also thought to be involved in inducing breast, testicular, and prostate 

cancers, as well as endometriosis (Berger 1994; Giwercman et al. 1993; Hoel et al. 1992). 

Selenium is a component of all three members of the deiodinase enzyme family, the enzymes responsible 

for deiodination of the thyroid hormones (Köhrle 1994; St. Germain and Galton 1997). The deiodinases 
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contain a selenocysteine at the active site, which is required for catalytic activity. There are three types of 

deiodinases and they differ in terms of tissue distribution, reaction kinetics, efficiency of substrate 

utilization, and sensitivity to inhibitors. The first to be recognized as a selenoprotein was type I 

iodothyronine 5'-deiodinase, which converts the prohormone thyroxine (T4) to the active form, 

triiodothyronine (T3) and to date, studies of the effects of excess selenium have focused on this protein. 

Under normal circumstances, the human thyroid produces only 20–30% of its hormone as T3; the 

remainder is T4 (a minute amount of reverse T3 (rT3) is also produced), which is largely converted to 

active T3 by type I deiodinase located within the liver, euthyroid pituitary, kidney, thyroid, and brain. 

Type I deiodinase is a membrane bound protein and, thus, its activity has not been directly measured in 

studies of humans supplemented with selenium. Human studies have instead measured serum levels of 

T3, rT3, T4, and TSH. 

Two human studies have demonstrated a decrease in T3 levels in response to increased dietary selenium 

although the hormone levels remained within the normal human range (Brätter and Negretti De Brätter 

1996; Hawkes and Turek 2001). The effect of increased dietary selenium on other thyroid hormones is 

unclear. No significant correlation between selenium intake and serum T4 or TSH levels was found in the 

study of Brätter and Negretti De Brätter (1996), although Hawkes and Turek (2001) showed that TSH 

concentration increased (+37%) and was significantly different relative to baseline levels (p<0.06) in a 

high selenium group. In a third study of the effects of selenium supplementation, New Zealanders with 

normally low selenium intake (unsupplemented intake of 28–29 μg/day) showed a reduction in T4 

concentration in all groups after 20 weeks (Duffield et al. 1999). A significant inverse correlation was 

found between serum levels of selenium and TSH among fish consumers; however, it is not known if this 

population had a high selenium intake (Hagmar et al. 1998). 

Male rats receiving diets supplying 0.05mg selenium/kg/day for 6–12 weeks have been shown to have 

reductions in type-I-deiodinase activity (Behne et al. 1992; Eder et al. 1995; Hotz et al. 1997). However, 

the levels of thyroid hormones in these animals have not shown a consistent pattern. Exposure to 

0.055 mg selenium/kg/day as sodium selenite for 40 days produced a significant decrease in serum levels 

of T3 (Eder et al. 1995). In another study, a dose of 0.09 mg selenium/kg/day as sodium selenate in food 

for 6 weeks produced a significant (~30%) increase in TSH (Hotz et al. 1997), and no significant changes 

in thyroid levels of T3 or T4 were found in rats receiving 0.105 mg selenium/kg/day as sodium selenite or 

0.118 mg selenium/kg/day as L-selenomethionine for 3 months (Behne et al. 1992). 
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Many studies have documented reduced body weight gain in young animals treated with selenium 

compounds and abnormal weight loss in older animals (Grønbaek et al. 1995; Halverson et al. 1966; Harr 

et al. 1967; Jacobs and Forst 1981a; Nelson et al. 1943; NTP 1994; Johnson et al. 2000; Palmer and Olson 

1974; Panter et al. 1996; Schroeder 1967; Tsunoda et al. 2000). There is evidence to suggest that these 

effects may be due in part to the interactions of selenium or selenium compounds with hormones that 

regulate normal growth and body weight. Reduced insulin-like growth factor-binding protein-3, growth 

hormone secretion in response to growth hormone releasing factor, and somatomedin C levels have been 

reported in rats exposed to sodium selenite in drinking water (Grønbaek et al. 1995; Thorlacius-Ussing et 

al. 1988), although somatomedin C was not a sensitive end point in humans from a high selenium area of 

South Dakota (Salbe et al. 1993). 

No studies were located regarding adverse effects on human reproduction following oral exposure to 

elemental selenium or to selenium compounds. However, data from animal studies suggest that oral 

exposure to selenium may be associated with male infertility. Adverse effects associated with selenium 

exposure include decreased sperm counts in rats and rabbits (El-Zarkouny et al. 1999; Kaur and Parshad 

1994; NTP 1994), sperm abnormalities in rats and rabbits (El-Zarkouny et al. 1999; Kaur and Parshad 

1994), testicular hypertrophy in rats (Turan et al. 1999a), and a significant reduction in serum testosterone 

in rabbits (El-Zarkouny et al. 1999). However, it is not clear what effect, if any, this had on the ability of 

the animals to reproduce, as chronic administration of selenate did not affect male fertility in rats or mice 

(Rosenfeld and Beath 1954; Schroeder and Mitchener 1971b). 

Chronic exposure of mice and rats to otherwise nontoxic doses has been shown to reduce fertility and to 

markedly reduce the viability of the offspring of pairs that are able to conceive (Schroeder and Mitchener 

1971b; Wahlstrom and Olson 1959b). Selenium exposure has been shown to alter the length of the 

estrous cycle in female mice (Nobunaga et al. 1979) and to alter the menstrual cycle in monkeys 

(Cukierski et al. 1989). Vaginal cytology of female rats provided with drinking water containing selenate 

or selenite indicated that the rats spent more time in diestrus and less time in proestrus and estrus than the 

controls (NTP 1994). However, it is not clear what effect, if any, this had on the ability of the animals to 

reproduce. 

Fertility studies in mice, rats, and pigs have demonstrated reduced rates of conception after oral treatment 

with selenium as selenate or selenite (Rosenfeld and Beath 1954; Schroeder and Mitchener 1971b; 

Wahlstrom and Olson 1959b). Decreased conception rates and increased resorption rates have been 

reported for cattle, sheep, and horses fed diets naturally containing organic selenium compounds and 
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exhibiting symptoms of selenosis (Harr and Muth 1972). An increased concentration of progesterone in 

the milk and an association of cystic ovaries with elevated blood selenium concentrations was observed in 

cows receiving selenium supplementation (Mohammed et al. 1991). 

Other possible examples of endocrine disruption due to selenium exposure include pancreatic damage in 

sheep and rats fed selenium as sodium selenite, sodium selenate, or seliniferous wheat (Halverson et al. 

1966; Harr et al. 1967; Smyth et al. 1990) and decreased plasma glucose (an insulin-like effect) in rats 

injected with sodium selenate. However, these are isolated reports and it is not clear what relevance they 

have for selenium toxicity in humans. 

3.7 CHILDREN’S SUSCEPTIBILITY 

This section discusses potential health effects from exposures during the period from conception to 

maturity at 18 years of age in humans, when all biological systems will have fully developed. Potential 

effects on offspring resulting from exposures of parental germ cells are considered, as well as any indirect 

effects on the fetus and neonate resulting from maternal exposure during gestation and lactation. 

Relevant animal and in vitro models are also discussed. 

Children are not small adults. They differ from adults in their exposures and may differ in their 

susceptibility to hazardous chemicals. Children’s unique physiology and behavior can influence the 

extent of their exposure. Exposures of children are discussed in Section 6.6 Exposures of Children. 

Children sometimes differ from adults in their susceptibility to hazardous chemicals, but whether there is 

a difference depends on the chemical (Guzelian et al. 1992; NRC 1993). Children may be more or less 

susceptible than adults to health effects, and the relationship may change with developmental age 

(Guzelian et al. 1992; NRC 1993). Vulnerability often depends on developmental stage. There are 

critical periods of structural and functional development during both prenatal and postnatal life and a 

particular structure or function will be most sensitive to disruption during its critical period(s). Damage 

may not be evident until a later stage of development. There are often differences in pharmacokinetics 

and metabolism between children and adults. For example, absorption may be different in neonates 

because of the immaturity of their gastrointestinal tract and their larger skin surface area in proportion to 

body weight (Morselli et al. 1980; NRC 1993); the gastrointestinal absorption of lead is greatest in infants 

and young children (Ziegler et al. 1978). Distribution of xenobiotics may be different; for example, 

infants have a larger proportion of their bodies as extracellular water and their brains and livers are 
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proportionately larger (Altman and Dittmer 1974; Fomon 1966; Fomon et al. 1982; Owen and Brozek 

1966; Widdowson and Dickerson 1964). The infant also has an immature blood-brain barrier (Adinolfi 

1985; Johanson 1980) and probably an immature blood-testis barrier (Setchell and Waites 1975). Many 

xenobiotic metabolizing enzymes have distinctive developmental patterns. At various stages of growth 

and development, levels of particular enzymes may be higher or lower than those of adults, and 

sometimes unique enzymes may exist at particular developmental stages (Komori et al. 1990; Leeder and 

Kearns 1997; NRC 1993; Vieira et al. 1996). Whether differences in xenobiotic metabolism make the 

child more or less susceptible also depends on whether the relevant enzymes are involved in activation of 

the parent compound to its toxic form or in detoxification. There may also be differences in excretion, 

particularly in newborns who all have a low glomerular filtration rate and have not developed efficient 

tubular secretion and resorption capacities (Altman and Dittmer 1974; NRC 1993; West et al. 1948). 

Children and adults may differ in their capacity to repair damage from chemical insults. Children also 

have a longer remaining lifetime in which to express damage from chemicals; this potential is particularly 

relevant to cancer. 

Certain characteristics of the developing human may increase exposure or susceptibility, whereas others 

may decrease susceptibility to the same chemical. For example, although infants breathe more air per 

kilogram of body weight than adults breathe, this difference might be somewhat counterbalanced by their 

alveoli being less developed, which results in a disproportionately smaller surface area for alveolar 

absorption (NRC 1993). 

Selenium is known to be an essential micronutrient for humans and animals; therefore, inadequate as well 

as excessive selenium intake can cause adverse health effects. The Food and Nutrition Board of the 

National Research Council has established adequate intakes (AI) of 15–20 μg/day for infants based on the 

selenium content of milk of well nourished, but unsupplemented, mothers (NAS 2000). No data were 

available on which to base RDAs for children or adolescents; thus, the RDAs for children and adolescents 

are extrapolated from adult values. Studies of selenium deficient populations suggest that children are 

more susceptible to the effects of selenium deficiency and have the highest need for selenium of any 

individuals in the population (Chen et al. 1980; Yang et al. 1988). Premature and full-term infants 

generally have significantly lower blood selenium levels than their mothers and/or normal adults 

(Gathwala and Yadav 2002). Infants born prematurely have lower hepatic selenium stores than term 

infants at birth, indicating that premature infants are at particular risk for the development of a deficiency 

state if adequate selenium is not provided in the diet (Bayliss et al. 1985). 
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Limited information is available relevant to the toxicity of selenium in children. Observations from the 

early literature, particularly in livestock and chickens, suggest that young animals are less resistant to 

selenium than older ones (NAS 1976a; Rosenfeld and Beath 1964b), and a study in rats found that 

weanlings accumulated more selenium in their tissues than adults (Salbe and Levander 1989). In contrast, 

the available information in humans suggests that children may be less susceptible to toxic effects of 

selenium than adults. Most data come from children living in areas of chronic high dietary selenium 

intake (Yang et al. 1989a, 1989b). Children (aged 3–12 years) in a seleniferous area of China were found 

to have a significantly higher intake of selenium than the adults in their community, but a corresponding 

increase in blood levels of selenium appeared only in the children aged 7–12. When the incidence of 

selenosis in different age groups was examined, it was found that 97% of cases were older than 18 years, 

and no cases were observed in children below 12 years of age, even though selenium intakes per kg body 

weight and blood selenium levels in these age groups were found to be either higher than or equal to those 

of affected adults. One study of children living in a seleniferous area of Venezuela found a significant 

increase in the percentage of children showing lower than normal height compared with controls from a 

nonseleniferous area (Brätter et al. 1991a). However, these children also had very low intakes of zinc 

compared with controls (10–25% of controls), and it is likely that their reduced growth rate is due to 

inadequate intake of zinc. Another study that compared children from seleniferous and non-seleniferous 

areas of Venezuela found slightly reduced height, weight, hemoglobin levels, and hematocrit values for 

the children from the seleniferous area (no statistical analysis was performed), although no clinical signs 

of selenosis were observed (Jaffe et al. 1972). However, the children from the seleniferous zone had a 

poorer diet, consumed less milk and meat, and had a greater incidence of intestinal parasites, which may 

account for the differences observed. 

No adverse developmental effects of excess selenium have been reported for humans. Excess selenium is 

a demonstrated teratogen in birds (Franke and Tully 1935; Franke et al. 1936; Gruenwald 1958; Khan and 

Gilani 1980; Palmer et al. 1973), but there is no clear evidence linking selenium exposures to developmental effects in mammals. Malformations have been reported for livestock that consumed naturally high 

seleniferous diets (Dinkel et al. 1963; Rosenfeld and Beath 1964), but it is not clear that these reports took 

into account consumption of other toxic range plants. Other studies of developmental effects in livestock 

receiving controlled diets with known amounts of selenium have generally not observed abnormalities, 

reduced birth weights, or increased mortality (Panter et al. 1995; Yaeger et al. 1998). Likewise, studies of 

laboratory animals have not observed developmental effects, except at levels of selenium administration 

that produce maternal toxicity (Bergman et al. 1990; Chiachun et al. 1991; Ferm et al. 1990; NTP 1996; 

Poulsen et al. 1989; Rosenfeld and Beath 1954; Schroeder and Mitchener 1971b; Thorlacius-Ussing 
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3. HEALTH EFFECTS 

1990). In a teratology study of long-tailed macaques, no gross abnormalities or growth retardations were 

observed in fetuses from mothers administered doses that produced maternal toxicity. 

No studies were located that compared pharmacokinetic properties of selenium in humans or animals of 

different ages. Selenium is transferred to fetuses via the placenta (Archimbaud et al. 1992; Choy et al. 

1993; Hawkes et al. 1994; Jandial et al. 1976; Mahan and Kim 1996) and to infants via breast milk 

(Brätter and Negretti De Brätter 1996; Brätter et al. 1991b; Li et al. 1999; Michalke and Schramel 1998; 

Moser-Veillon et al. 1992; Rodríguez Rodríguez et al. 1999; Viitak et al. 1995; Yang 1989b). Studies of 

lactating women have shown a clear relationship between levels of selenium in the mother’s diet and the 

concentration of selenium in her breast milk (Brätter et al. 1991b). Colostrum contains more than twice 

the selenium concentration of mature human milk, but the selenium content of mature milk changes little 

with advancing stages of lactation (Gathwala and Yadav 2002; Higashi et al. 1983; Mannan and Picciano 

1987; Smith et al. 1982). No information was located regarding adverse effects in infants breast-fed by 

mothers in regions with high selenium diets. 

A series of conditions are associated with oxygen therapy in neonates, including bronchopulmonary 

dysplasia, retinopathy of prematurity, necrotizing enterocolitis, patent ductus arteriosus, and neuronal 

injury in hypoxic ischemic encephalopathy (Gathwala and Yadav 2002). Because these effects might be 

caused at least in part by oxygen radicals, it has been suggested there is an “oxygen radical disease” in 

neonatology. This indicates that antioxidants may form an important modality of treatment in neonates, 

and because selenium is part of the antioxidant enzyme glutathione peroxidase, good selenium nutrition is 

important for antioxidant defense (Gathwala and Yadav 2002). 

3.8 BIOMARKERS OF EXPOSURE AND EFFECT 

Biomarkers are broadly defined as indicators signaling events in biologic systems or samples. They have 

been classified as markers of exposure, markers of effect, and markers of susceptibility (NAS/NRC 

1989). 

Due to a nascent understanding of the use and interpretation of biomarkers, implementation of biomarkers 

as tools of exposure in the general population is very limited. A biomarker of exposure is a xenobiotic 

substance or its metabolite(s) or the product of an interaction between a xenobiotic agent and some target 

molecule(s) or cell(s) that is measured within a compartment of an organism (NAS/NRC 1989). The 

preferred biomarkers of exposure are generally the substance itself or substance-specific metabolites in 
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readily obtainable body fluid(s), or excreta. However, several factors can confound the use and 

interpretation of biomarkers of exposure. The body burden of a substance may be the result of exposures 

from more than one source. The substance being measured may be a metabolite of another xenobiotic 

substance (e.g., high urinary levels of phenol can result from exposure to several different aromatic 

compounds). Depending on the properties of the substance (e.g., biologic half-life) and environmental 

conditions (e.g., duration and route of exposure), the substance and all of its metabolites may have left the 

body by the time samples can be taken. It may be difficult to identify individuals exposed to hazardous 

substances that are commonly found in body tissues and fluids (e.g., essential mineral nutrients such as 

copper, zinc, and selenium). Biomarkers of exposure to selenium are discussed in Section 3.8.1. 

Biomarkers of effect are defined as any measurable biochemical, physiologic, or other alteration within an 

organism that, depending on magnitude, can be recognized as an established or potential health 

impairment or disease (NAS/NRC 1989). This definition encompasses biochemical or cellular signals of 

tissue dysfunction (e.g., increased liver enzyme activity or pathologic changes in female genital epithelial 

cells), as well as physiologic signs of dysfunction such as increased blood pressure or decreased lung 

capacity. Note that these markers are not often substance specific. They also may not be directly 

adverse, but can indicate potential health impairment (e.g., DNA adducts). Biomarkers of effects caused 

by selenium are discussed in Section 3.8.2. 

A biomarker of susceptibility is an indicator of an inherent or acquired limitation of an organism's ability 

to respond to the challenge of exposure to a specific xenobiotic substance. It can be an intrinsic genetic or 

other characteristic or a preexisting disease that results in an increase in absorbed dose, a decrease in the 

biologically effective dose, or a target tissue response. If biomarkers of susceptibility exist, they are 

discussed in Section 3.10 “Populations That Are Unusually Susceptible”. 

3.8.1 Biomarkers Used to Identify or Quantify Exposure to Selenium 

Biomarkers of exposure are available for high and low exposures to selenium. Selenium can be detected 

in the blood, feces, urine, hair, and nails of exposed individuals. Both selenium deficiency and excessive 

levels of selenium are associated with several disorders. For purposes of comparison, reported mean 

selenium concentrations in whole blood, blood constituents, urine, hair, nails, and the placenta for healthy 

individuals living in the United States and several other countries are listed in Table 3-7. Based on 

information collected from 1988 to 1994 in the third National Health and Nutrition Examination Survey 

(NHANES III), the serum concentration of selenium in the U.S. population has been estimated by sex and 
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age (DHHS 1997). The mean selenium serum concentration for all ages and both sexes was estimated to 

be 0.125 mg/L. Additional results from NHANES III are summarized in Chapter 6 (Section 6.5, 

Table 6-6). The analytical methods used to measure selenium (described in Chapter 7) have improved, 

and the more recent studies may be more reliable. The values for the Chinese populations studied by 

Yang et al. (1983, 1989b) were those reported for individuals living in the selenium "adequate" regions 

included in the study. "Normal" selenium concentrations in blood constituents and other tissues in people 

from some countries (e.g., New Zealand) are generally lower than those in people living in the United 

States. In general, urinary excretion rates of 20–200 μg selenium/day are not associated with either 

selenium deficiency or toxicity (Sanz Alaejos and Diaz Romero 1993). 

In the United States and other developed countries, hair selenium concentrations are not necessarily 

indicative of dietary exposure to environmental selenium. Users of therapeutic dandruff shampoos 

containing selenium sulfide may have high levels of selenium in their hair because the externally 

deposited selenium adsorbs to hair (Alfthan 1985). However, due to minimal levels of dermal absorption 

of selenium from shampoo, blood and urine levels are not significantly affected by selenium-containing 

shampoos (Howe 1979). Toenail samples have also been used as biomarkers of selenium exposure 

(Hunter et al. 1990a). Selenium levels in toenails were measured in volunteers who ate bread containing 

selenium for 1 year (Longnecker et al. 1993). During this time period, selenium in the large toenail did 

not reach a steady state, while a steady state was reached in the other toenails. After conclusion of the 

1-year exposure, levels of selenium continued to decline until they reached baseline levels in 2 years. 

Below plasma and whole blood selenium concentrations of 0.10 mg selenium/L, a positive correlation has 

been reported between blood selenium levels and both erythrocyte and whole blood GPX activity 

(Duffield et al. 1999; Perona et al. 1977; Thomson 1977; Valentine et al. 1988). GPX is an enzyme that 

acts as a scavenger of peroxides and protects cells from oxidative damage. However, whole blood 

selenium levels ≤0.10 mg selenium/L represent the lower end of the range of whole blood selenium 

concentrations reported by Allaway et al. (1968) for American males. 

A correlation between blood selenium levels and GPX activity was not observed when plasma and whole 

blood selenium levels were above 0.10 mg selenium/L. Therefore, GPX activity is likely to be a 

biomarker for selenium deficiency but not for overexposure. Neve et al. (1988), on the other hand, found 

no relationship between erythrocyte or plasma GPX activity levels and plasma selenium levels in a group 

of Belgian subjects with plasma selenium levels between 0.087 and 0.13 mg selenium/L. However, 

platelet GPX activity levels did correlate with plasma selenium levels within this range (Neve et al. 1988). 
SELENIUM 185 

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Valentine et al. (1980) measured the level of selenium in whole blood, urine, and hair of 33 residents 

from a Mexican village who consumed drinking water contaminated with selenium (0.026–1.8 mg 

selenium/L) from a uranium mill tailing pond. Blood levels ranging from 0.133 to 0.248 mg selenium/L, 

urine excretion rates ranging from 14.4 to 337.5 μg selenium/day, and hair selenium levels ranging from 

0.02 to 1.98 μg selenium/g were not correlated with GPX activity. In examining the relationship between 

selenium and GPX activity, selenium-dependent GPX activity must be distinguished from nonseleniumdependent GPX activity (Edwards and Blackburn 1986). 

Selenoprotein P, which contains 10 selenocysteines, is the principal selenoprotein found in plasma (Sunde 

1990). Selenoprotein P in plasma also does not continue to increase with increasing selenium and has 

been suggested as an alternative to GPX as a biomarker for selenium status (Duffield et al. 1999; Huang 

et al. 1995). The function of selenoprotein P has still not been determined. 

Field studies have used primarily blood or urine levels to indicate the degree of selenium exposure. 

Valentine et al. (1978) found a significant correlation between selenium levels in well water used for 

drinking and urine selenium excretion measured for 35 residents in a New Mexico community. However, 

no correlation was found between selenium levels in well water and the blood selenium levels of the 

35 residents (Valentine et al. 1978). The correlation coefficients between the log of urine-selenium 

excretion (μg selenium/day) and the log of blood-selenium (mg selenium/L) with the log of the well water 

selenium concentration (mg selenium/L) were 0.57 (p<0.01) and 0.14 (p>0.05), respectively. The 

correlation coefficient between the log of hair selenium concentration (μg selenium/g) and the log of the 

well water selenium levels (mg selenium/L) was 0.45 (p<0.01). 

Methylation is a detoxification pathway for selenium, and the extent of methylation is dose-dependent. 

Monomethylated selenium is excreted in the urine at deficient, normal, and low-toxic levels of selenium, 

and excretion of trimethylated selenium increases at toxic doses (Kobayashi et al. 2002). The main 

monomethylated form of selenium has been identified as a selenosugar (1β-methylselenol-N-acetyl-Dgalactosamine). The dose-dependent nature of the metabolism indicates that urinary monomethylated 

(selenosugar) and trimethylated selenium could be used as indicators of selenium exposure that increase 

within the required to low-toxic range and with a distinct toxic dose, respectively (Kobayashi et al. 2002). 

Clinical symptoms have been associated with excessive blood, urine, and hair levels of selenium in 

exposed patients. Glover (1967) examined workers in a selenium rectifier factory and found that 

selenium levels in urine from workers exposed to selenium (annual averages from 1954 and 1958 range 
SELENIUM 186 

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from 0.076 to 0.109 mg selenium/L urine) were higher than the average urine selenium levels of 

preemployment applicants (average, 0.034 mg selenium/L urine; range, 0–0.15 mg selenium/L). Garlic 

breath, skin rashes, indigestion, lassitude, and irritability were noted, but no increase in mortality among 

exposed workers was detected. Smith and Westfall (1937) examined urine selenium levels in rural 

populations in Wyoming, South Dakota, and Nebraska and reported evidence of skin discoloration and 

lesions, tooth decay, diseased nails, gastrointestinal disturbances, and arthritis in individuals with urine 

selenium levels of 0.2–1.98 mg selenium/L; however, the authors did not find a significant correlation 

between clinical signs and the level of selenium in the urine. Longnecker et al. (1991) examined ranchers 

in the same area of the United States where selenosis of livestock had been observed. No clinical effects 

were observed with concentrations up to 2.2 mg/L in urine. Yang et al. (1983, 1989a, 1989b) measured 

mean blood, urine, and hair selenium levels of 3.2 mg selenium/L, 2.68 mg selenium/L, and 32.2 μg 

selenium/g, respectively, in a high selenium area where chronic selenosis was common in China. The 

clinical signs of selenium intoxication included loss of hair and nails, skin lesions, tooth decay, and 

nervous system disorders. In another area of China with high environmental levels of selenium but no 

signs of chronic selenosis in the population, blood selenium levels averaged 0.44 mg selenium/L (with a 

range from 0.35 to 0.58 mg selenium/L). 

At blood levels of 0.06–0.20 mg selenium/L, Deguchi (1985) found selenium to be positively correlated 

with grasping power and blood pressure in normal men and women and with hematocrit and hemoglobin 

concentrations in normal women. Similar correlations were not found in subjects with proteinuria or 

hypertension. In addition, Gebre-Medhin et al. (1988) found that in healthy children, serum selenium 

levels of 0.055–0.082 mg selenium/L were positively correlated with serum cholesterol, serum 

triglycerides, low and very low density lipoproteins, and apolipoproteins. Similar correlations were not 

found in diabetic children, who have slightly elevated serum selenium levels. 

Biomarkers of Deficiency. Two endemic diseases, Keshan disease and Kashin-Beck disease, have been 

reported in selenium-deficient populations in China in which mean hair, blood, and urine selenium levels 

are low (Yang et al. 1988). Acute Keshan disease, manifested as nausea, vomiting of yellowish fluid, and 

necrosis of the myocardium, has been found in a population with an average whole blood selenium 

concentration of 0.018 mg selenium/L, an average urinary concentration of 0.007 mg selenium/L, and an 

average hair selenium concentration of 0.123 μg/g (Yang et al. 1988). Kashin-Beck disease, which 

causes atrophy, degeneration, and necrosis of cartilage tissue, was observed in selenium-deficient areas in 

China, in which the average selenium concentration in hair ranged from 0.077 to 0.165 μg selenium/g and 

blood selenium concentrations averaged approximately 0.02 mg selenium/L. In nonaffected areas in 
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China, the selenium content is >0.2 μg selenium/g in hair and >0.06 mg selenium/L in blood (Yang et al. 

1988). Although the association between selenium deficiency and Kashin-Beck disease is unclear, 

selenium-deficiency diseases are unlikely to occur in persons in the United States. If selenium is not 

added to parenteral nutrition solutions, persons on long-term total parenteral nutrition are at risk for 

developing selenium deficiency symptoms which include cardiomyopathies, muscle pain, and weakness 

(Thomson 1991). 

There is also some evidence that low serum selenium levels are associated with increased cancer risk, but 

this is not conclusive (Hojo 1981a; Willett et al. 1983). Salonen et al. (1984) concluded that an increased 

risk of cancer (a combination of gastrointestinal, respiratory, urogenital, hematologic, dermal, and skeletal 

cancers) in humans in Finland is associated with serum selenium levels of 0.045 mg selenium/L and 

below. Virtamo et al. (1987) found that cancer patients in Finland, including individuals with 

gastrointestinal, respiratory, skin, skeletal, urogenital, and hematological cancers, had slightly but not 

significantly lower serum selenium levels (mean and standard error of 0.0539±0.0015 mg selenium/L) 

compared with noncancer patients (0.0553±0.0005 mg selenium/L). However, serum selenium is 

generally an indicator only of very recent selenium status. As such, serum selenium may indicate an 

effect of cancer (malabsorption or anorexia) rather than a cause (Lockitch 1989; van't Veer et al. 1990). 

A deficiency of selenium is also associated with cardiomyopathy (Johnson et al. 1981; Oster et al. 1983). 

Salonen et al. (1982) noted a statistically significant association between serum selenium concentrations 

of less than 0.045 mg selenium/L and the adjusted relative risk of coronary death, cardiovascular death, 

and myocardial infarction. Hojo (1981a) noted that patients with epilepsy had significantly lower urinary 

selenium levels than controls. 

3.8.2 Biomarkers Used to Characterize Effects Caused by Selenium 

Specific biomarkers were not found for effects of excess selenium, indicating that better markers of 

effects are needed at high levels of exposure. Garlic breath is a marker of over-exposure to selenium 

compounds. However, as other metals that are methylated (e.g., arsenic) also result in garlic odor of the 

breath, this effect is not a unique marker of selenium over-exposure. Hair and nail effects may be the 

most frequent effects of overexposure to selenium. Hair becomes dry and brittle and breaks off at the 

scalp. Nails are also brittle and have white spots and longitudinal streaks, and break off easily (Lockitch 
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1989). Although these effects may not be specific to selenium, if they are observed, a determination of 

selenium status may be useful. 

Yang et al. (1989b) used increased prothrombin time (increased clotting time), a measure of hepatic 

damage, as a biomarker for selenium but their interpretation of their observations may be unwarranted. 

The difference they saw in affected humans was very small (1 second); prothrombin time has not been 

previously demonstrated to correlate with symptoms of selenosis nor used to detect selenosis; and since 

the test has not been widely used, the results reported for the small number of affected individuals may be 

within the range of normal values for the general population or a subpopulation (IRIS 2003). 

In humans and in animal studies, high concentrations of selenium have been demonstrated to cause 

neurological effects. Biomarkers of effect for the neurological system have been reviewed by ATSDR 

(OTA 1990). 

3.9 INTERACTIONS WITH OTHER CHEMICALS 

A wide variety of interactions of selenium with essential and nonessential elements, vitamins, 

xenobiotics, and sulfur-containing amino acids have been demonstrated in numerous studies. Selenium 

has been reported to reduce the toxicity of many metals including mercury, cadmium, lead, silver, and to 

some extent, copper (Frost 1972; Levander 1982). Most forms of selenium and arsenic interact to reduce 

the toxicity of both elements (Levander 1977). Because of selenium's role in the antioxidant glutathione 

peroxidase enzymes, selenium also reduces the toxicity of metals in vitamin E-deficient animals (Diplock 

et al. 1967). 

The interactions of selenium with other elements and compounds are complex and not well understood 

(Naganuma et al. 1983; NAS 1976a). The degree to which selenium is toxic, is taken up by tissues, or is 

excreted can be influenced by these interactions. Some of the major interactions of selenium compounds 

with other elements and compounds are described below. 

Arsenic. In general, arsenic antagonizes selenium toxicity (Levander 1977). This effect extends to 

selenium in sodium selenite and selenate, seleniferous wheat, selenocystine, and selenomethionine 

(Levander 1977). However, a very pronounced synergistic toxicity exists between arsenic and two 

methylated selenium metabolites, trimethylselenonium ion and dimethyl selenide (Obermeyer et al. 
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3. HEALTH EFFECTS 

1971). One of the more striking demonstrations is the antagonism of arsenic-induced terata in rodents by 

concomitant selenium exposure (Holmberg and Ferm 1969), and pretreatment of mice with sodium 

selenite reduced the clastogenic effects of a subsequent dose of sodium arsenite (Biswas et al. 1999b). 

Moxon et al. (1945) found that arsenic could reduce selenium toxicity when compounds of both elements 

were injected subcutaneously, thereby indicating that arsenic did more than interfere with the 

gastrointestinal absorption of selenium. Kamstra and Bonhorst (1953) found that arsenic reduced the 

excretion of volatile selenium compounds in expired air following the injection of compounds of both 

elements into rats at acutely toxic levels. Levander and Baumann (1966a) found that the amount of 

selenium retained in the liver decreased and the amount of selenium appearing in the gastrointestinal tract 

increased as the dose of administered arsenic was increased. Experiments with rats and guinea pigs with 

cannulated bile ducts confirmed that arsenic increased the biliary excretion of selenium and that selenium 

increased the biliary excretion of arsenic (Levander and Baumann 1966b). It has recently been suggested 

that the mutual reduction in toxicity of arsenic and selenium administered together is due to the formation 

of an arsenic-selenium compound, seleno-bis(S-glutathionyl)arsinium (Gailer et al. 2000b). This 

compound was isolated from the bile of rabbits injected with selenium and arsenic and identified by X-ray 

spectroscopy. 

Cadmium. Selenium can antagonize the nephrotoxic and hepatotoxic effects of cadmium in rats (Flora et 

al. 1982; Lindh et al. 1996; Nehru and Bansal 1996; Stajn et al. 1997), the inflammation, atrophy, and 

necrosis induced by cadmium in testes of rats (Jones et al. 1997; Mason and Young 1967; Ohta and 

Imamiya 1986; Wlodarczyk et al. 1995; Yiin et al. 1999), and the cardiotoxicity of cadmium in rats 

(Jamall et al. 1989). The protective effects are thought to occur as a result of the formation of a seleniumcadmium complex of high molecular weight (Chen et al. 1975; Jamall et al. 1989; Jamba et al. 1997; Ohta 

and Imamiya 1986). 

Fluoride. Fluoride ion may interact with selenium; however, the degree and types of interaction depend 

upon the chemical form of selenium (i.e., organic or inorganic) and the dose. Moxon and DuBois (1939) 

reported that fluoride increased the toxicity of selenium in rats at 5 mg fluoride/L in the drinking water of 

young rats fed a diet containing 11 ppm selenium (0.55 mg selenium/kg/day) as seleniferous wheat. 

Selenium decreased growth and increased mortality in rats drinking fluoridated water compared to rats 

drinking deionized water. These results were disputed by Hadjimarkos (1969a) who administered 3 mg 

selenium/L as sodium selenite (0.15 mg selenium/kg/day) either with or without 50 mg fluoride/L as 

sodium fluoride in the drinking water of rats. The growth and mortality data indicated that the combined 

administration of selenium and fluoride under the conditions used did not increase selenium toxicity. 
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3. HEALTH EFFECTS 

However, the amount of administered fluoride was significantly higher and the amount of administered 

selenium was significantly lower in the Hadjimarkos (1969a) study than the amounts administered by 

Moxon and DuBois (1939). No additional studies were located that reexamined the possible interaction 

between fluoride and selenium. 

Iodine. Selenium and iodine interact to affect thyroid function. There are at least two aspects to this 

interaction. First, selenium is an important component of the deiodinase enzymes, including 

iodothyronine 5'-deiodinases, which convert the prohormone thyroxine (T4) to the active circulating form, 

triiodothyronine (T3) (Delange 2000; Köhrle 1994; St Germain and Galton 1997). Second, selenium is 

also a component of GPX, the main enzyme responsible for protecting thyroid cells against oxidative 

damage. Hydrogen peroxide (H2O2) is produced in the thyroid during the conversion of T4 to T3 and is 

detoxified by GPX. An apparent consequence of interaction between iodine and selenium has been 

observed in human populations deficient in iodine. In some iodine-deficient geographic regions, a 

reversible hypothyroidism with goiter formation (myxedematous cretinism) is observed (Goyens et al. 

1987; Vanderpas et al. 1990). In other iodine-deficient areas, hypothyroidism is accompanied by thyroid 

cell necrosis. The thyroid cell necrosis appears to result in populations that are deficient in both iodine 

and selenium (Contempré et al. 1991a, 1992, 1993, 1995; Köhrle 1994). Selenium supplementation of 

individuals deficient in both iodine and selenium produces a further decrease in thyroid function, but if 

selenium supplementation is preceded by normalization of iodine levels, then normal thyroid function is 

restored (Contempré et al. 1991, 1992). Selenium supplementation also affects thyroid hormone levels in 

humans with no iodine deficiency; these effects include decreases in serum T3 and T4 levels and increases 

in serum TSH levels, suggesting suppression of thyroid hormone production (Brätter and Negretti De 

Brätter 1996; Duffield et al. 1999; Hagmar et al. 1998; Hawkes and Turek 2001). The necrotizing effect 

of iodine on thyroid cells was greater in selenium-deficient rats than in selenium-supplemented rats 

(Contempré et al. 1993). Other studies in rats showed that selenium deficiency causes decreased 

metabolic clearance of iodothyronines and decreased extrathyroidal production of T3, as a result of 

decreased iodothyronine deiodinase activity, which can be restored to normal by selenium repletion 

(Arthur and Beckett 1989, 1994; Behne and Kyriakopolous 1993). The effects observed in iodine and 

selenium deficient humans and animals is consistent with a proposed mechanism in which (1) iodine 

deficiency results in hyperstimulation of the thyroid by TSH and consequently in increased production of 

H2O2 within the cells, (2) selenium deficiency results in GPX deficit and consequently in accumulation of 

H2O2, and (3) induction of thyroid cell necrosis and fibrosis from the excess H2O2 that cannot be 

detoxified due the lack of GPX (Contempré et al. 1995; Delange 2000; Köhrle 1994). The available data 

suggest that iodine supplements could cause adverse effects in selenium-deficient individuals. 
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3. HEALTH EFFECTS 

Mercury. Simultaneous administration of mercury and selenium in equimolar doses to animals resulted 

in decreased toxicity of both elements in acute and chronic studies with inorganic and organic mercury 

and with either inorganic or organic selenium compounds, although inorganic forms of selenium appear 

to be more effective than organic forms (Chang 1983; Rao et al. 1998; Skerfving 1978). Selenium 

protects against the acute nephrotoxicity of the mercuric ion and methylmercuric ion in rats (Ganther et 

al. 1972; Hansen 1988; Magos et al. 1987; Parizek and Ostadalova 1967) and possibly against acute 

neurotoxicity of the methylmercuric ion in rats (Ohi et al. 1980). The protective effect of selenium has 

been associated with a higher whole body retention of mercury rather than with increased mercury 

excretion (Hansen 1988; Magos et al. 1987). Selenium has been shown to inhibit biliary excretion of 

methyl mercury in rats (Urano et al. 1997), while mercury exposure reduces urinary selenium excretion in 

humans (Ellingsen et al. 1995). Although the mechanism of the interaction has not yet been elucidated, 

selenium and mercury appear to form a metabolically inert compound by reaction with GSH (Gailer et al. 

2000b). Further support for the role of this compound comes from the observation that selenium-treated 

animals can remain unaffected despite an accumulation of mercury in tissues to levels that are otherwise 

associated with toxicity (Skerfving 1978). Additional support comes from the 1:1 ratio of selenium and 

mercury found in the livers of marine mammals and in the bodies of experimental animals injected with 

mercury and selenium, regardless of the ratio of the administered doses (Hansen 1988). 

Although the fetotoxicity of methylmercuric chloride has been enhanced in selenium-deficient mice 

(Nishikido et al. 1987), additional selenium administration does not appear to protect against teratogenic 

effects (i.e., cleft palate) of methylmercuric chloride in mice (Lee et al. 1979). High doses of selenium 

administered as selenite for 30 days prior to gestation and through gestation day 18 to mice fed a diet 

containing high doses of methylmercuric chloride increased the incidence of cleft palate (Nobunaga et 

al. 1979). Concurrent treatment of pregnant or lactating mice receiving nontoxic doses of methyl mercury 

in drinking water with selenomethionine increased the deposition of mercury in the offspring (Nielsen and 

Andersen 1995). 

Methionine and Vitamin E. Combinations of methionine and vitamin E have been found to be 

antagonistic to selenium toxicity. In one study, selenium concentrations in the liver and kidneys of rats 

fed selenium (sodium selenate)-containing diets with methionine and vitamin E were less than the 

concentrations found in the livers and kidneys of rats fed selenium with either methionine or vitamin E 

alone (Levander and Morris 1970). The results are compatible with the hypothesis that methionine 

detoxifies selenium by forming methylated derivatives of selenium that are eliminated in the urine and in 
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3. HEALTH EFFECTS 

expired air (see Section 3.4.4) (Stadtman 1977, 1980, 1983, 1987, 1990). As discussed in Section 3.11, 

methionine administered as an antidote for acute selenium toxicity in rats was ineffective (Lombeck et al. 

1987). 

Silver. Selenium has been shown to be protective against the hepatotoxic effects of silver in vitamin Edeficient rats. A 0.15% solution of silver acetate in the drinking water of rats produced necrotic 

degeneration of the liver and high mortality. Dietary selenium supplementation at 1 mg selenium/kg food 

resulted in a significant reduction in the toxic effects of silver (Diplock et al. 1967). One report indicates 

a nontoxic dose of silver acetate in rats minimizes effects of acute selenium toxicity. However, the body 

burden of selenium in several organs increased with treatment with silver acetate. It is postulated that this 

antagonistic effect may be due to the formation and disposition of silver selenides, which are relatively 

insoluble and nontoxic (Eybl et al. 1992). 

Sulfate. Sulfate appears to reduce the growth inhibition that results from dietary exposure of rats to high 

levels of selenite or selenate (Halverson and Monty 1960). Sulfate does not appear to be protective 

against selenium-induced liver damage (Halverson and Monty 1960). 

Antagonistic interactions with several additional metals including antimony, germanium, and bismuth 

have been reported (Paul et al. 1989). Complex interactions of selenium with other metals, vitamins, and 

nutrients usually lead to a reduced toxicity of selenium and/or a reduced toxicity of the interacting 

substance. However, vitamin C (ascorbic acid) may increase the absorption and toxic effects of selenium 

in humans (HSDB 2001; Lombeck et al. 1987; Mack 1990; Martin et al. 1989a, 1989b). The relevance of 

these interactions to selenium exposure of the general public is unknown. Many review articles are 

available concerning the interactions of selenium and other chemicals, including those by Combs, Jr., and 

Combs (1987), Hansen (1988), Levander (1972), Magos and Webb (1980), Naganuma et al. (1983), and 

Whanger (1981). 

3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE 

A susceptible population will exhibit a different or enhanced response to selenium than will most persons 

exposed to the same level of selenium in the environment. Reasons may include genetic makeup, age, 

health and nutritional status, and exposure to other toxic substances (e.g., cigarette smoke). These 

parameters result in reduced detoxification or excretion of selenium, or compromised function of organs 
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3. HEALTH EFFECTS 

affected by selenium. Populations who are at greater risk due to their unusually high exposure to 

selenium are discussed in Section 6.7, Populations With Potentially High Exposures. 

Data concerning human subpopulations with unusual susceptibility to the toxic effects of selenium were 

not located. Epidemiologic studies have identified populations with very low or very high nutritional 

status, and these groups are expected to have very different responses to selenium exposures. Pregnant 

and nursing women are believed to require more selenium than the general public (NRC 1989). 

It is possible that persons exposed to high fluoride levels in drinking water might be at greater risk of 

adverse health effects from exposure to excessive levels of selenium (Moxon and DuBois 1939; Yang et 

al. 1989a), but evidence on this point is equivocal (Hadjimarkos 1969a) and requires further study. 

Individuals with vitamin E-deficient diets might also be at greater risk of liver damage from exposure to 

excess selenium (Levander and Morris 1970). Based on studies of chemically induced diabetes in rats, 

selenium may change insulin needs (McNeil et al. 1991). Therefore, insulin-dependent diabetics may be 

more sensitive to adverse health effects due to selenium exposure than the general population. 

Cretins or other individuals with iodine or thyroid deficiencies may be more sensitive to adverse health 

effects from selenium exposure (Contempré et al. 1991b, 1992). Iodine supplementation of these 

individuals without selenium supplementation may further exacerbate the effects. The elderly may be 

less susceptible to the negative effects of selenium and more prone to selenium deficiencies. A number of 

researchers have reported lower absorption of selenium and lower selenium tissue concentrations in the 

elderly compared to younger adults (Martin et al. 1991; Morisi et al. 1989). 

Populations living in the western United States in areas eating produce grown in highly seleniferous soils 

could be at greater risk of adverse health effects from additional environmental exposure to selenium if 

their selenium nutritional status is already high (see Section 6.6). 

3.11 METHODS FOR REDUCING TOXIC EFFECTS 

This section will describe clinical practice and research concerning methods for reducing toxic effects of 

exposure to selenium. However, because some of the treatments discussed may be experimental and 

unproven, this section should not be used as a guide for treatment of exposures to selenium. When 

specific exposures have occurred, poison control centers and medical toxicologists should be consulted 
SELENIUM 194 

3. HEALTH EFFECTS 

for medical advice. The following texts provide specific information about treatment following exposures 

to selenium: 

Nadig RJ. 1994. Cadmium and other metals and metalloids. In: Goldfrank LR, Weisman RS, 

Flomenbaum N, et al. eds. Goldfrank’s toxicological emergencies. 6th ed. Norwalk, CT: Appleton and 

Lange, 1342-1343. 

Mofenson HC, and Caraccio TR. 1998. Toxicity of household products. In: Viccellio P, ed. 

Emergency toxicology. 2nd ed. Philadelphia, PA: Lippincott-Raven, 519. 

3.11.1 Reducing Peak Absorption Following Exposure 

No specific recommendations have been reported for reducing absorption following acute high-dose 

exposure to selenium or selenium compounds via inhalation or dermal exposure (Gosselin et al. 1984; 

HSDB 2001). There have been very few reported cases of overexposure via inhalation in industrial 

settings but some have resulted in toxic effects (Lockitch 1989). General procedures suggested for 

reducing absorption following accidental industrial exposure include moving the exposed person into 

fresh air, removing contaminated clothing and shoes, and flushing exposed skin or eyes with running 

water (HSDB 2001). 

Oral exposures to toxic quantities of selenious acid, sodium selenate, and selenium dioxide have been 

reported (Lockitch 1989). In general, only supportive treatment has been recommended (HSDB 2001; 

Mack 1990). In some cases, gastric lavage and induction of vomiting by use of emetics have been 

reported to be useful in reducing absorption, but because selenious acid (in gun bluing, pH 1) is caustic, 

both procedures could result in additional damage by this compound (Lombeck et al. 1987; Mack 1990). 

The possibility of a sudden onset of shock, seizures, severe hypotension, and cardiorespiratory arrest has 

been used to argue against emesis (Mack 1990). It has also been suggested that oils and alcohol are to be 

avoided in treatment of ingested selenium sulfide because these agents may increase absorption (Gosselin 

et al. 1984). 

3.11.2 Reducing Body Burden 

In acute exposure situations, selenium compounds are rapidly absorbed and widely distributed throughout 

many organ systems following inhalation or ingestion (see Section 3.4.2). Extensive parenteral fluid 

administration has been used to force the urinary excretion of selenium (Lombeck et al. 1987). Chelating 
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3. HEALTH EFFECTS 

agents have not been effective in experiments, and both calcium disodium ethylene diamine tetraacetate 

(EDTA) and dimercaprol (British Anti-Lewisite, BAL) may increase the toxic effects of selenium 

(Lombeck et al. 1987; Mack 1990; Paul et al. 1989). Although vitamin C (ascorbic acid) is used to reduce 

the body burdens of other metals, it may also increase the absorption and toxic effects of selenium in 

humans (HSDB 2001; Lombeck et al. 1987; Mack 1990; Martin et al. 1989a, 1989b). Bromobenzene has 

been reported to increase the urinary excretion of selenium, but because bromobenzene is also a hepatic 

toxin, its use is dangerous (Gosselin et al. 1984; HSDB 2001). 

3.11.3 Interfering with the Mechanism of Action for Toxic Effects 

The exact molecular mechanism of toxic action by selenium and selenium compounds is not known. One 

theory is that at a biochemical level, selenium inactivates sulfhydryl enzymes leading to depression of 

cellular oxidative processes (Lombeck et al. 1987; Mack 1990; Shamberger 1981). No information was 

located on established therapies designed to interfere with this possible mechanism of action of selenium. 

Because selenomethionine is known to randomly insert into proteins, rats were treated with methionine 

after acute selenosis had developed, but no effect was observed (Lombeck et al. 1987). However, 

pretreating rats with dietary methionine and vitamin E reduced the toxicity of dietary selenium as 

measured by decreased liver damage, reduced body weight gain, and decreased liver and kidney 

concentrations of selenium compared to those in rats that had not received supplements (Levander and 

Morris 1970). Inorganic sulfate fed simultaneously with selenite or selenate in the diet protected rats 

from the toxicity of selenium as measured by body weight gain; however, sulfate did not protect against 

liver necrosis caused by selenium (Halverson et al. 1962). It would, therefore, seem plausible that another 

nontoxic sulfur-containing chemical could be found to be effective against acute selenium toxicity. 

The search for an agent that both reduces the acute toxicity of selenium and increases the excretion of the 

selenium compound formed has proved difficult (Paul et al. 1989). In some experimental cases, other 

metals have been shown to mitigate the toxicity of selenium, possibly by forming metal selenides with 

low solubility and toxicity (see Section 3.9). Several metal-containing compounds were tested for 

efficacy in reducing toxic effects and increasing elimination of selenium from sodium selenate injected 

into rats. Germanium citrate is nontoxic and was found to be effective both at reducing toxic effects and 

increasing the rate of selenium elimination. However, the germanium compound, bis-carboxyethyl 

germanium sesquioxide, had no positive effect on toxicity or distribution to organs but did increase the 

amount of selenium excreted in the urine (Paul et al. 1989). In mice, pretreatment with a nontoxic dose of 
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3. HEALTH EFFECTS 

silver acetate was shown to reduce the toxic effects of sodium selenite. However, this treatment increased 

the whole body burden of selenium, and the concentrations in several organs were raised compared to 

those in the controls injected with sodium selenite only (Eybl et al. 1992). Arsenic was proposed as a 

possible prophylactic against selenium poisoning in workers, based on counteraction of selenium toxicity 

in pigs exposed to sodium arsenate (Amor and Pringle 1945). 

3.12 ADEQUACY OF THE DATABASE 

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with the 

Administrator of EPA and agencies and programs of the Public Health Service) to assess whether 

adequate information on the health effects of selenium is available. Where adequate information is not 

available, ATSDR, in conjunction with the National Toxicology Program (NTP), is required to assure the 

initiation of a program of research designed to determine the health effects (and techniques for developing 

methods to determine such health effects) of selenium. 

The following categories of possible data needs have been identified by a joint team of scientists from 

ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that if met would 

reduce the uncertainties of human health assessment. This definition should not be interpreted to mean 

that all data needs discussed in this section must be filled. In the future, the identified data needs will be 

evaluated and prioritized, and a substance-specific research agenda will be proposed. 

3.12.1 Existing Information on Health Effects of Selenium 

The existing data on health effects of inhalation, oral, and dermal exposure of humans and animals to 

selenium are summarized in Figure 3-10. The purpose of this figure is to illustrate the existing 

information concerning the health effects of selenium. Each dot in the figure indicates that one or more 

studies provide information associated with that particular effect. The dot does not necessarily imply 

anything about the quality of the study or studies, nor should missing information in this figure be 

interpreted as a “data need”. A data need, as defined in ATSDR’s Decision Guide for Identifying 

Substance-Specific Data Needs Related to Toxicological Profiles (Agency for Toxic Substances and 

Disease Registry 1989), is substance-specific information necessary to conduct comprehensive public 

health assessments. Generally, ATSDR defines a data gap more broadly as any substance-specific 

information missing from the scientific literature. 
SELENIUM 197 

3. HEALTH EFFECTS 

Figure 3-10. Existing Information on Health Effects of Selenium 
SELENIUM 198 

3. HEALTH EFFECTS 

As seen in Figure 3-10, very little quantitative information is available regarding the health effects in 

humans exposed to selenium compounds via inhalation. The only quantitative inhalation studies in 

humans that relate selenium exposure levels or selenium body levels to health effects following inhalation 

exposure are epidemiological cancer studies. Fatalities following inhalation exposure to selenium 

compounds have not been reported. Despite the large number of cases of reported inhalation exposures in 

occupational settings, characterization of exposure concentrations and the selenium compounds present in 

the air are generally lacking. It is therefore not possible to link the degree and types of symptoms 

reported in workers to selenium exposure levels. There have been no reports of immunological, 

developmental, reproductive, or genetic effects in humans resulting from inhalation exposure to selenium 

compounds. Complaints of dizziness and fatigue have accompanied occupational inhalation exposures, 

but characterization of the exposure levels required to produce neurological symptoms is lacking. 

Most of the information concerning the health effects in humans following exposure to selenium and 

selenium compounds is for the oral exposure route. However, exposure levels associated with the few 

documented fatalities resulting from accidental or suicidal poisoning with selenium compounds are 

lacking, as are exposure levels for other nonfatal poisonings by ingestion. A series of epidemiological 

studies in China have provided the only data about chronic exposure levels to excess dietary selenium that 

resulted in adverse effects on skin, nails, and hair and in possible neurological effects. 

Older reports from the western United States described similar symptomology in the 1930s, but did not 

characterize daily selenium intake. More recent reports show no clinical symptoms in the same area. The 

possible inverse relationship between dietary selenium intake and the risk of various types of cancer has 

been examined in numerous epidemiological studies in the United States and other countries. 

Concern for the dermal route of exposure to selenium compounds as a cause of adverse health effects in 

humans is extremely low except for the acid forms, which owe their dermal effects to their acidity more 

than to their selenium content. Selenium sulfide, an ingredient in some antidandruff shampoos, does not 

appear to be absorbed through the skin. Ingestion of large amounts of the compound, however, would be 

of concern because selenium sulfide has been shown to be carcinogenic in rats and mice following oral 

exposure. 

Data are available for acute inhalation exposures for a few of the volatile selenium compounds that have 

resulted in the death of animals. These exposures also produced signs of central nervous system toxicity, 
SELENIUM 199 

3. HEALTH EFFECTS 

lung injury, and possible damage to heart and liver. No studies were located concerning health effects in 

animals following intermediate or chronic inhalation exposures to volatile selenium compounds or 

selenium dust. 

In animals, the focus on the oral toxicity of selenium has taken two routes, one in laboratory animals and 

the other in studies of selenium toxicity to livestock. In laboratory animals, attention has been directed 

toward the hepatotoxic properties of selenites, selenates, and selenium contained in grains following early 

reports that selenium produced hepatic carcinomas in rats. An intermediate-duration study has also 

shown that selenate and selenite can cause kidney effects in rats while mice are less sensitive to this effect 

of selenium compounds. In recent years, much of the research in laboratory animals using the oral route 

of administration of selenium compounds has been directed toward the anticarcinogenic properties of 

selenium compounds. 

In livestock, concern for selenium toxicity and deficiency is high. In areas of the country with seleniumpoor soils, dietary selenium supplementation for livestock has been necessary to prevent chronic selenium 

deficiency diseases. Dietary supplementation programs have resulted in cases of accidental poisonings 

from misuse of the selenium supplements (Hopper et al. 1985). 

3.12.2 Identification of Data Needs 

Acute-Duration Exposure. The primary target organ in humans following acute exposure to high 

concentrations of selenium by inhalation or oral routes is the lung, with cardiovascular, hepatic, and renal 

systems all affected (lesser systemic effects were observed in all other organ systems except the 

musculoskeletal system) (Carter 1966; Civil and McDonald 1978; Clinton 1947; Koppel et al. 1986; 

Wilson 1962). Two case reports of acute dermal exposure were also located; the results revealed effects 

on the skin and eyes (Middleton 1947; Pringle 1942). Additional epidemiological or occupational studies 

would be useful to further characterize the effects of acute exposure via all routes and to confirm the 

target organ data. 

Studies regarding single inhalation or oral exposures of rats, guinea pigs, rabbits, and mice have provided 

information on lethal levels of exposure to selenium compounds (Cummins and Kimura 1971; Dudley 

and Miller 1941; Hall et al. 1951; Miller and Williams 1940; Olson 1986; Smyth et al. 1990). However, 

few levels at which sublethal effects first appear have been identified. Clinical observations and gross 
SELENIUM 200 

3. HEALTH EFFECTS 

necropsies have been performed, but no single-dose exposure study has included internal examination of 

the animals to identify dose-response data for sublethal systemic toxic effects. Such studies might 

provide information on the thresholds for systemic toxicity following single-dose exposure. Repeated 

inhalation exposure studies in animals are limited to a few days of exposure (Hall et al. 1951). Although 

the studies have demonstrated cumulative toxicity following repeated inhalation exposure to inorganic 

selenium compounds, effects other than lethality have been poorly characterized. Single-dose exposure 

studies have been conducted with selenium monosulfide in mice (target systems: respiratory and 

neurological) and selenium disulfide in rats (target organ not specified); however, the results have varied 

and there is uncertainty about which or how much of each of the compounds was administered. There 

were no effects in mice following acute dermal exposure. Additional dermal exposure studies in animals 

would be useful to confirm the effects found in humans. The data were insufficient for the derivation of 

acute oral and inhalation MRLs. 

Intermediate-Duration Exposure. No human studies of intermediate inhalation exposure to 

selenium were located. Following oral exposure, one study in humans revealed endocrine effects in 

iodine-deficient individuals (Contempré et al. 1991a, 1992) and others revealed endocrine effects in 

individuals receiving sufficient levels of iodine (Duffield et al. 1999; Hawkes and Turek 2001). Results 

from one study in humans revealed dermal effects following intermediate dermal exposure (Pringle 

1942). There were insufficient data to derive intermediate MRLs. Additional epidemiological or 

occupational studies would be useful in elucidating the potential target organs and effect levels. 

No intermediate inhalation studies were located in animals. Intermediate-duration inhalation studies, in 

which selenium is administered as selenium dioxide, hydrogen selenide, or selenium dust, might help to 

identify air concentrations of these substances that produce sublethal effects not only on the respiratory 

system, but also on the hepatic, renal, hematological, and cardiovascular systems. As exposure to the 

selenoamino acids is via ingestion, inhalation studies of these compounds would not be necessary. 

Intermediate-duration oral exposure studies have been performed with rats, pigs, mice, and monkeys at 

several dose levels using several selenium compounds (Baker et al. 1989; Behne et al. 1992; BioulacSage et al. 1992; Chen et al. 1993; Cukierski et al. 1989; Das et al. 1989b; Eder et al. 1995; Halverson et 

al. 1966; Hasgawa et al. 1994; Hotz et al. 1997; Mahan and Magee 1991; Mihailovic et al. 1992; NTP 

1980c, 1994; Palmer and Olson 1974; Panter et al. 1996). The major effects were hepatic, dermal, 

endocrine, and neurological. Additional studies are needed to confirm these data. No intermediateduration dermal administration studies have been conducted with the environmental forms of inorganic 
SELENIUM 201 

3. HEALTH EFFECTS 

selenium likely to be of concern (e.g., sodium selenate and sodium selenite), although it is unlikely that 

these forms would be dermally absorbed to a significant degree. Dermal application of selenomethionine 

to the skin of mice did not result in any direct effects on the skin, or other signs of toxicity, although it 

was absorbed (Burke et al. 1992b). The organic compounds of selenium are usually not free in the 

environment but, rather, are contained in plant and animal material. Therefore, no further dermal studies 

would be useful. 

Chronic-Duration Exposure and Cancer. Several occupational studies of chronic inhalation 

exposure to inorganic selenium compounds were located (Glover 1967; Holness et al. 1989; Kinnigkeit 

1962). Effects reported in these studies were primarily respiratory, although cardiovascular, gastrointestinal, hematological, musculoskeletal, dermal, ocular, and neurological effects were also noted. 

Animal data are not available for inhalation exposures of chronic duration. Data in this area would be 

helpful to establish an animal model for respiratory effects of inorganic selenium compounds, since most 

human exposure has been occupational and to a variety of compounds. Neurological effects have been 

documented in animals after chronic oral exposure, but further study of neurological effects in animals 

after inhalation exposure is needed to provide a model for the effects observed after occupational 

exposure in humans. Following chronic oral exposure, the primary effects in humans were dermal, 

neurological, and endocrine (Brätter and Negretti De Brätter 1996; Clausen et al. 1989; Longnecker et al. 

1991; Yang et al. 1983, 1989a, 1989b; Yang and Zhou 1994). An MRL has been derived for chronic oral 

exposure to selenium based on a NOAEL for dermal effects. One case report of chronic dermal exposure 

revealed dermal effects (Senff et al. 1988). Additional epidemiological or retrospective studies of chronic 

exposure would be helpful for confirming the existing data. Studies examining the role of nutrition in 

selenium toxicity would be especially useful. 

Although the lung does not appear to be a target organ in animals after chronic oral exposure to selenium 

compounds, data have not been adequately reported (Harr et al. 1967; Henschler and Kerschner 1969; 

Schroeder and Mitchener 1972), and further studies might be useful to fully rule out these effects. Studies 

examining possible gastrointestinal and musculoskeletal effects in animals after chronic exposure to 

selenium or selenium compounds or to seleniferous grains might be helpful in determining the 

mechanisms of alkali disease whose symptoms have been observed in grazing livestock (Harr et al. 1967; 

Shamberger 1986). Hepatic and renal lesions following chronic selenium exposure have been adequately 

characterized. Investigations of systemic effects associated with chronic oral administration of selenium 

compounds, however, have been limited. 
SELENIUM 202 

3. HEALTH EFFECTS 

No studies were located regarding carcinogenic effects in animals after chronic inhalation exposure to 

selenium or selenium compounds. No further investigation is needed since humans have not been shown 

to have an increased risk of malignancy from selenium exposure. The majority of oral studies have 

provided information on the absence of carcinogenic effects in humans and animals (Beems 1986; Clark 

et al. 1996a, 1999; Coates et al. 1988; Duffield-Lillico et al. 2002; Harr et al. 1967; Menkes et al. 1986; 

Reid et al. 2002; Thompson and Becci 1979; Virtamo et al. 1987). However, earlier and less complete 

studies had suggested that selenium was carcinogenic following oral exposure of animals (Nelson et al. 

1943; Schroeder and Mitchener 1971a; Volgarev and Tscherkes 1967). Chronic oral exposure studies 

conducted in mice and rats by gavage administration of a mixture of selenium monosulfide and selenium 

disulfide produced liver tumors in rats and lung tumors in female mice (NTP 1980c). The relative 

proportion of the two compounds was not clear, although physical evidence suggested that the dose 

solution was primarily selenium monosulfide. Further studies utilizing selenium sulfides might be useful 

in determining possible effects in humans. 

Genotoxicity. Chromosomal aberrations and sister chromatid exchanges in lymphocytes were not 

increased in humans treated (oral or intramuscular injection) with sodium selenite (Norppa et al. 1980a). 

Compared to untreated controls, a significant increase in the number of micronuclei was observed in bone 

marrow cells of mice treated orally with selenite or selenate, and macaques treated orally with 

L-selenomethionine (Biswas et al. 1997, 1999a; Choy et al. 1989; Itoh and Shimada 1996; Rusov et al. 

1996). A significant increase in the number of micronuclei in bone marrow cells was not observed in the 

offspring of macaques treated with L-selenomethionine on gestation days 20–50 (Choy et al. 1993). 

Genotoxicity studies (Salmonella/microsome assays, sister chromatid exchange, and tests of unscheduled 

DNA synthesis and of chromosome aberrations in cultured mammalian cells) indicate that selenite, 

selenate, and selenide have both genotoxic and antigenotoxic effects (Biswas et al. 1997, 2000; Gairola 

and Chow 1982; Khalil 1994; Lu et al. 1995b; Schillaci et al. 1982; Ueda et al. 1997; van der Lelie et al. 

1997). The underlying mechanisms responsible for the varying genotoxicity results remain to be 

elucidated. 

Reproductive Toxicity. One study that measured the concentration of selenium in sperm samples 

indicated no correlation between selenium concentrations and sperm count or motility (Roy et al. 1990). 

No significant increase in spontaneous abortions was reported among women chronically exposed to 

drinking water containing 7–9 μg/L selenium (Vinceti et al. 2000a). This study is limited by a level of 

selenium in water that is not generally considered to be high, lack of data on selenium status, and 
SELENIUM 203 

3. HEALTH EFFECTS 

insufficient information on confounding variables. No other human studies were located. A few 

reproductive toxicity studies in animals (Chowdhury and Venkatakrishna-Bhatt 1983; Harr and Muth 

1972; NTP 1996; Schroeder and Mitchener 1971b; Wahlstrom and Olson 1959b) indicate that oral 

exposure to excess sodium selenite can reduce female fertility, although male fertility appears not to be 

affected. Oral treatment of rats with sodium selenate or selenite has been shown to increase the number 

of abnormal sperm in males (El-Zarkouny et al. 1999; Kaur and Parshad 1994; NTP 1994), produce 

testicular hypertrophy (Turan et al. 1999a), and affect the estrous cycle (NTP 1994, 1996). Fertility was 

not examined in these studies. Selenium dioxide produced testicular degeneration following 

intraperitoneal administration to rats (Chowdhury and Venkatakrishna-Bhatt 1983). Disturbances in the 

menstrual cycle (anovulation, short luteal and follicular phases) were observed in monkeys treated orally 

with L-selenomethionine (Cukierski et al. 1989) and mice treated orally with sodium selenite (Nobunaga 

et al. 1979). Studies of both male and female reproductive toxicity of selenium following oral and 

inhalation exposure in rats and other mammals to selenium dioxide and other forms of selenium, both 

organic and inorganic, would be useful. Such studies could provide information regarding the 

reproductive effects of the various forms of selenium that might be encountered in occupational settings, 

at waste sites, and in the drinking water and food from highly seleniferous areas of the United States. 

Developmental Toxicity. No developmental studies were found regarding inhalation or dermal 

exposure in humans or animals. Developmental studies using the oral route of administration indicate 

that excessive sodium selenate or sodium selenite intake can result in fetal toxicity and reduced growth in 

experimental mammals (Dinkel et al. 1963; Ferm et al. 1990; NTP 1996; Rosenfeld and Beath 1964; 

Wahlstrom and Olson 1959a), but generally only at doses that produce maternal toxicity. Developmental 

effects were not observed in macaque fetuses from mothers given toxic oral doses of L-selenomethionine 

during gestation (Tarantal et al. 1991). Intravenous injection of sodium selenite in mice did not indicate 

that the compound is teratogenic in rodents (Yonemoto et al. 1984). Intravenous injections of sodium 

selenate, D,L-selenomethionine, and D,L-selenocystine into neonatal rats indicated that some selenium 

compounds can contribute to the formation of one type of cataracts (Ostadalova and Babicky 1980). 

Cataracts were not observed in the offspring of macaques treated orally with L-selenomethionine during 

gestation (Tarantal et al. 1991). Additional developmental toxicity studies of selenium compounds in 

mammals do not seem to be necessary at this time. 

Immunotoxicity. No studies were located regarding adverse immunological effects in humans 

following inhalation or oral exposure. One case report describes immunological effects following dermal 

exposure (Senff et al. 1988). Animal studies of possible adverse immunological effects from excessive 
SELENIUM 204 

3. HEALTH EFFECTS 

exposure to selenium compounds are limited (Dudley and Miller 1941; Glenn et al. 1964a; Hall et al. 

1951; Smyth et al. 1990). One study (Koller et al. 1986) included a battery of immunological tests, some 

of which indicated beneficial effects of sodium selenite administration and others that indicated adverse 

effects. Additional immunotoxicity tests, including challenges of the immune system, might characterize 

the significance of the different immunological effects that have been observed following selenium 

administration. 

Other than selenium sulfide, an ingredient in some antidandruff shampoos, selenium compounds have not 

been tested for sensitization. The potential for dermal contact by humans does exist, however, in 

occupational settings and to a lesser extent in soil at waste sites. 

Neurotoxicity. Data from an epidemiological study of humans and from studies in livestock indicate 

that the central nervous system is an end point of concern following oral exposure to selenium compounds 

(Baker et al. 1989; Boylan et al. 1990; Cukierski et al. 1989; Harrison et al. 1983; Panter et al. 1996; 

Rosenfeld and Beath 1964; Stowe et al. 1992; Tsunoda et al. 2000; Yang et al. 1983). Chronic oral 

exposure studies of laboratory animals that focus on behavioral effects and histopathological changes in 

the central nervous system might provide useful dose-response information on central nervous system 

effects. 

Epidemiological and Human Dosimetry Studies. A few human epidemiological studies have 

identified blood selenium levels indicative of adequate selenium status and indicative of selenium 

toxicity. However, there are large differences in selenium blood levels in populations from different parts 

of the world (e.g., China, New Zealand, and Finland) (Salonen et al. 1985; Yang et al. 1989a). For 

example, blood selenium levels in healthy New Zealand populations averaged 0.059 mg selenium/L (Rea 

et al. 1979), whereas blood selenium levels in healthy U.S. populations were much higher, averaging 

0.206 mg selenium/L (Allaway et al. 1968). Extrapolation from the relationship between blood selenium 

levels and selenium toxicity in populations from one region of the world to populations in another region 

may not be appropriate. Studies examining the particular forms of selenium and the contribution of diet 

in determining individual and population selenium status would be useful. The selenium status of an 

individual will determine the magnitude of additional selenium intake that can be tolerated without 

resulting in adverse effects. Evidence for adverse effects on the endocrine system has also been found 

following intermediate and chronic oral exposure to elevated levels of dietary selenium in humans and 

animals (Brätter and Negretti De Brätter 1996; Behne et al. 1992; Eder et al. 1995; Hawkes and Turek 

2001; Hotz et al. 1997). Studies of humans with high dietary intakes of selenium that monitored thyroid 
SELENIUM 205 

3. HEALTH EFFECTS 

hormone levels and iodine intake would be useful. Studies of humans taking selenium supplements 

would also help further identify the long-term effects of selenium status on human health. 

Biomarkers of Exposure and Effect. 

Exposure. Selenium exposure can be correlated with concentrations detected in human blood, blood 

components, urine, hair, and nails. Selenium concentrations found in these biomarkers in the general 

population can be found in Table 3-7. However, these markers vary greatly among different populations 

(Longnecker et al. 1991). Levels of plasma, erythrocyte and platelet GPX activity, as well as 

selenoprotein P may serve as better markers of selenium deficiency than selenium concentrations. 

Additional research into markers of selenium status in populations and how they may be used to estimate 

an additional selenium exposure that would be safe would be helpful. 

Effect. There currently are no good preclinical indicators of selenium toxicity. Perhaps the earliest and 

most frequent symptoms of selenosis in humans are dry and brittle hair that breaks off, and brittle nails 

with white spots or streaks. Although these effects may not be specific to selenium, determination of 

selenium status could be useful if they are observed in a subject. Additional biomarkers of negative 

effects that could be detected before clinical signs of selenium toxicity would be helpful in identifying 

and preventing selenium poisoning. 

Absorption, Distribution, Metabolism, and Excretion. The absorption of selenium has been 

investigated in humans following oral exposure and in animals following oral and inhalation exposures 

(Finley 1998; Glover 1970; Griffiths et al. 1976; Martin et al. 1989a; Medinsky et al. 1981a; SánchezOcampo et al. 1996; Thomson et al. 1977). In humans, no quantitative data exist on either the extent or 

rate of absorption of selenium from the lung or the skin. Information that selenium is absorbed following 

inhalation is limited to occupational case studies in which larger quantities of selenium have been 

measured in the urine of workers occupationally exposed to selenium. In order to understand all possible 

routes for human overexposure to selenium, information concerning the dermal and inhalation absorption 

of selenium and its compounds in humans would be useful, even though potential exposures to selenium 

might be more likely to occur by the oral route for the general public. 

The oral absorption of different physical and chemical forms of selenium (e.g., selenite, selenate, and 

selenomethionine as solids or in aqueous solution) has been investigated in humans (Griffiths et al. 1976; 

Martin et al. 1989a; Moser-Veillon et al. 1992; Robinson et al. 1978; Swanson et al. 1991; Thomson 
SELENIUM 206 

3. HEALTH EFFECTS 

1974; Thomson and Stewart 1974; Thomson et al. 1977) and in animals (Finley 1998; Furchner et al. 

1975; Thomson and Stewart 1973; Vendeland et al. 1992; Whanger et al. 1976). Oral absorption of 

naturally occurring selenium and the effects of dietary levels on the absorption of exogenous selenium 

have also been investigated (Young et al. 1982). These studies have revealed that several selenium 

compounds appear to be readily absorbed from the gastrointestinal tract of humans and animals. It also 

appears that the degree of absorption in humans is independent of the exposure level, but that in some 

cases, absorption is greater when a selenium deficiency exists. 

Distribution studies in humans and animals indicate that selenium is widely distributed in the body and is 

concentrated in the liver and kidney following oral, intravenous, or subcutaneous exposures (Cavalieri et 

al. 1966; Finley 1998; Heinrich and Kelsey 1955; Jereb et al. 1975; Kaneko et al. 1999; Mahan and Kim 

1996; Razagui and Haswell 1997; Shiobara et al. 1998; Thomson and Stewart 1973). Studies of 

intravenous administration of selenomethionine have indicated that animals and humans concentrate this 

compound in the pancreas, but it is unlikely that this selenium compound will be encountered in large 

quantities in the environment except in animals and plants along with other organic selenium compounds. 

It would be useful to know if selenomethionine concentrates in the pancreas of humans following oral 

intake. Following oral exposure, the distribution of selenium across the placenta into the fetuses of rats, 

hamsters, dogs, and monkeys (Archimbaud et al. 1992; Choy et al. 1993; Hawkes et al. 1994; Mahan and 

Kim 1996; Parizek et al. 1971a; Willhite et al. 1990) and the transfer of selenium from milk to suckling 

offspring of rats, dogs, and monkeys (Archimbaud et al. 1992; Choy et al. 1993; Hawkes et al. 1944; 

Parizek et al. 1971a) have also been investigated. Selenium levels have been measured in human milk 

(Brätter and Negretti De Brätter 1996; Brätter et al. 1991b; Li et al. 1999; Michalke and Schramel 1998; 

Moser-Veillon et al. 1992; Rodríguez Rodríguez et al. 1999; Viitak et al. 1995; Yang 1989b), and the 

concentration of selenium in human milk has been shown to correlate with dietary intake (Brätter et al. 

1991b). The uptake of selenium by erythrocytes and its subsequent metabolic alteration and ultimate 

binding to plasma proteins have been investigated (Sandholm 1973). 

The metabolism of selenium is now fairly well understood. To become incorporated into seleniumspecific proteins (e.g., glutathione peroxidase, thioredoxin reductase, iodothyronine 5'-deiodinase) 

through a cotranslational mechanism requires that selenium be in the form of selenide (Sunde 1990). All 

forms of selenium can be transformed to selenide, although the rates of transformation vary. For 

example, selenate is not converted to selenide as readily as selenite. The formation of selenide from 

selenocysteine requires a specific enzyme, selenocysteine β-lyase, which catalyzes the decomposition of 

selenocysteine to alanine and hydrogen selenide. Excess selenium can be methylated and exhaled or 
SELENIUM 207 

3. HEALTH EFFECTS 

excreted in the urine in both humans and animals. Further research is required to determine which 

selenium metabolites or intermediates lead to toxicity. 

In humans and animals, intravenous and oral administration data indicate that the major route of selenium 

excretion is in the urine (Byard and Baumann 1967; Davidson-York et al. 1999; Finley 1998; Griffiths et 

al. 1976; Palmer et al. 1970; Patterson et al. 1989; Shiobara et al. 1998; Swanson et al. 1991). Excretion 

of selenium in feces constitutes a minor pathway immediately following exposure, but the amount 

excreted can be equal to that excreted in urine depending on the chemical form of selenium administered, 

the size of the dose, and the length of time since dosing. Both human and animal studies indicate that the 

extent of excretion by any one route is related to the administered dose and the frequency of 

administration (Finley 1998; Lathrop et al. 1972; McConnell and Roth 1966; Shiobara et al. 1998; 

Thomson and Stewart 1974). The extent of excretion of selenium compounds in the expired air has been 

investigated in animals, but no quantitative studies in humans for this route exist; however, it is believed 

to be a minor pathway especially at lower doses (McConnell and Roth 1966; Olson et al. 1963). 

Comparative Toxicokinetics. The target organs and adverse health effects are generally similar 

across species. However, the liver appears to be the primary target organ for the oral toxicity of selenium 

in animals following intermediate and chronic exposure (Baker et al. 1989; Biolac-Sage et al. 1992; 

Fitzhugh et al. 1944; Halverson et al. 1970; Harr et al. 1967; Hasegawa et al. 1994; Kolodziejczyk et al. 

2000; Nelson et al. 1943; Palmer and Olson 1974; Sayato et al. 1993; Schroeder and Mitchener 1972; 

Skowerski et al. 1997a; Turan et al. 1999a), whereas liver cirrhosis or dysfunction have not been found in 

reports of chronic selenosis in humans (Longnecker et al. 1991; Yang et al. 1989a). Different metabolites 

may help explain the cataract formation observed in neonatal rats and the teratogenic activity of selenium 

seen in birds but not in humans or other mammals (Tarantal et al. 1991). Toxicokinetic studies with some 

design similarities have been performed in humans and several animal species (Behne et al. 1991; Bopp et 

al. 1982; Cantor et al. 1975; Ganther 1979; Hawkes et al. 1992; Obermeyer et al. 1971; Palmer et al. 

1970; Willhite et al. 1990, 1992). Comparative toxicokinetic studies, per se, have not been performed. 

PBPK models for selenium administered orally as selenite or selenomethionine have been developed for 

humans, but no animal models were located. Animal models for the oral route would be useful in 

assessing toxicokinetic similarities and differences between species. 

Methods for Reducing Toxic Effects. Current methods for reducing toxic effects of selenium and 

selenium compounds after acute exposures are general supportive treatment methods based on those used 

for other toxic metals (HSDB 2001; Mack 1990). Because there is no suitable way to treat either acute or 
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3. HEALTH EFFECTS 

chronic selenium poisoning, additional research aimed at decreasing absorption, speeding excretion, and 

reducing the body burden of selenium would be valuable. 

Children’s Susceptibility. Limited information is available on the toxicity of selenium in children, 

but the available information suggests that children may be less susceptible to toxic effects of selenium 

than adults and more susceptible to deficiency. Most data comes from children living in areas of chronic 

high dietary selenium intake (Yang et al. 1989a, 1989b). Additional research on age specific effects of 

selenium toxicity does not appear necessary at present. 

Child health data needs relating to exposure are discussed in 6.8.1 Identification of Data Needs: 

Exposures of Children. 

3.12.3 Ongoing Studies 

The American Health Foundation is involved in on-going research to develop new organoselenium 

chemopreventive agents for cancer having an increased therapeutic ratio compared with some of the 

historical selenium compounds, such as selenite. Additional federally sponsored research that was 

reported in the CRIS/USDA (2002), CRISP (2002), and FEDRIP (2002) databases is shown in Table 3-8. 
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3. HEALTH EFFECTS 

Table 3-8. On-going Studies on Selenium Health Effects 

Investigator Institute Research area Reference 

Alberts, DS University of Arizona Phase III trials of chemopreventive CRISP 2001 

agents on colon carcinogenesis 

Aposhian, HV Not Available Detoxification of metals – In vitro and CRISP 2002 

in vivo studies 

Bar-Noy, S and National Institutes of Mammalian thioredoxin reductase FEDRIP 2002 

Nhlbi, NIH Health 

Beck, MA University of North The influence of nutrition on influenza FEDRIP 2002 

Carolina virus infection 

Bell, J Not available Effects of selected metal salts on the CRISP 2002 

fidelity of DNA synthesis in vitro 

Bennish, ML National Institutes of Micronutrients and enteric infection in FEDRIP 2002 

Health African children 

Beran, M Vyzkumny Ustav Evaluation of combined CRIS/UDSA 2001 

Potravinarsky supplementation with selenium and 

iodine on levels of seleniumdependent enzymes, thyroidal 

hormones and other biochemical 

parameters 

Berry, MJ Brigham and Women's Mechanism of selenoprotein CRISP 2001 

Hospital synthesis in eukaryotes 

Berry, MJ Brigham and Women's Selenoprotein P function and CRISP 2002 

Hospital regulation of expression 

Block, E Roswell Park Memorial Identify selenium compounds from CRISP 2001 

Institute high-selenium garlic 

Bosland, MC New York University Preclinical prostate cancer CRISP 2001 

School of Medicine chemoprevention studies 

Burk, RF Vanderbilt University Nutritional and metabolic significance FEDRIP 2002 

of selenium 

Burk, RF Vanderbilt University Selenium supplementation of patients CRISP 2001 

with cirrhosis 

Burk, RF Vanderbilt University Selenoprotein-P structure, function, CRISP 2001 

and activity 

Carlson, SG National Institutes of Antioxidant protection in age- FEDRIP 2002 

Health associated atherosclerosis 

Cassano, PA Cornell University Nutritional influences on lung disease CRIS/UDSA 2001 

Chirase, NK Texas A&M University Nutritional and environmental stress FEDRIP 2002 

and immune response of feeder cattle 

Chu, F-F National Institutes of Selenium-afforded protection against FEDRIP 2002 

Health atherosclerosis 

Clarke, LC University of Arizona Phase II chemoprevention trial of CRISP 2002 

selenium and prostate cancer 
SELENIUM 210 

3. HEALTH EFFECTS 

Table 3-8. On-going Studies on Selenium Health Effects 

Investigator Institute Research area Reference 

Clarke, LC and University of Arizona Randomized, controlled CRISP 2002 

Marshall, JR chemoprevention trials in populations 

at very high risk for prostate cancer: 

Elevated prostate-specific antigen 

and high-grade prostatic 

intraepithelial neoplasia 

Cohen, HJ Stanford University Relationship of the synthesis and CRISP 2001 

secretion of an extracellular selenium 

dependent glutathione peroxidase to 

changes in renal function 

Cohen, HJ Stanford University Selenium nutrition—Effects on blood FEDRIP 2002 

cell function 

Coltman, CA CTRC Research Chemoprevention of prostate cancer CRISP 2001 

Foundation 

Combs, GF Cornell University Characterization of antioxidant status FEDRIP 2002 

of a large cohort of free-living 

Americans 

Combs, GF Cornell University Dietary selenium and maintenance of FEDRIP 2002 

colonic health 

Combs, GF Cornell University Metabolic events at extremes of CRIS/UDSA 2001 

selenium intake; characterization of 

antioxidant status of a large cohort of 

free-living Americans 

Combs, GF Cornell University Kinetics of organic and inorganic CRIS/UDSA 2001 

selenium during dietary supplementation 

Costello, AJ University of Melbourne A randomized, controlled Costello 2001 

chemoprevention trial of selenium in 

familial prostate cancer: Rationale, 

recruitment, and design issues 

Davis, CD Agricultural Research Role of selenium in cancer CRIS/UDSA 2001 

Service susceptibility 

Diamond, AM University of Illinois Mechanism by which selenium CRISP 2001 

protects against mutagenesis 

Diamond, AM University of Illinois Selenium, aminothiols, and radiation CRISP 2002 

Doolittle, JJ South Dakota University Bioavailability of nutrients and FEDRIP 2002 

contaminants in soil 

Driscoll, DM Cleveland Clinic Mechanism of selenoperoxidase CRISP 2001 

Foundation biosynthesis 

Driskell, JA University of Nebraska Nutrient bioavailability: A key to FEDRIP 2002 

human nutrition 

El-Bayoumy, KE American Health Chemoprevention of oral cancer: CRISP 2001 

Foundation model studies 

El-Bayoumy, KE American Health Chemoprevention of lung cancer by CRISP 2002 

Foundation organoselenium: Model studies 
SELENIUM 211 

3. HEALTH EFFECTS 

Table 3-8. On-going Studies on Selenium Health Effects 

Investigator Institute Research area Reference 

El-Bayoumy, KE American Health Chemoprevention of mammary CRISP 2001 

Foundation cancer by organoselenium 

Fawzi, WW National Institutes of Trials of vitamins in HIV positive FEDRIP 2002 

Health progression and transmission 

Fiala, E American Health Organoselenium compounds as CRISP 2002 

Foundation modifiers of initiation/postinitiation 

carcinogenesis 

Finley, JW University of North Chemical forms of selenium in foods FEDRIP 2002 

Dakota 

Finley, JW Oregon State University Health benefits of high-selenium FEDRIP 2002 

foods to humans 

Funt, RC and Ohio State University Increasing the antioxidant level in FEDRIP 2002 

Clinton, S Ohio berries for potential prevention 

and intervention of certain cancers in 

humans 

Ganther, H Roswell Park Memorial Selenium metabolism and anti- CRISP 2001 

Institute carcinogenic action 

Ganther, H University of Wisconsin Organoselenium compounds 

biosynthesis and function 

Gesteland, RF University of Utah Genetic analysis of synthesis of CRISP 2001 

selenium containing proteins 

Gladyshev, VN University of Nebraska Biochemistry and molecular biology 

of selenium containing enzymes 

Gladyshev, VN University of Nebraska Identity of terminator and CRISP 2001 

selenocysteine UGA codons 

Glauert, HP University of Kentucky Effect of dietary antioxidants on 

hepatic NF-KB activation 

Gorbach, SL Tufts University Impact of micronutrients on FEDRIP 2002 

progression of SIV 

Gorbach, SL Harvard University Wasting, nutritional status, and FEDRIP 2002 

micronutrients 

Gottschall, EB National Jewish Medical Randomized, placebo-controlled, CRISP 2001 

and Research Center double blind trial of asbestos-exposed 

workers using high selenium yeast 

supplementation 

Gottschall, EB National Jewish Medical Selenium and lung cancer risk in CRISP 2002 

and Research Center asbestos workers 

Guttenplan, JB New York University Antimutagenesis by lycopene and CRISP 2001 

selenium in rodents 

Hakala TR Department of Veterans Select trial FEDRIP 2002 

Affairs 

Honn, KV Wayne State University Prostate cancer FEDRIP 2002 

Hurwitz. BE University of Miami Drug abuse, HIV, selenium FEDRIP 2002 

supplementation, and CVD risk 

CRIS/UDSA 2001 

CRIS/UDSA 2001 

CRIS/UDSA 2001 
SELENIUM 212 

3. HEALTH EFFECTS 

Table 3-8. On-going Studies on Selenium Health Effects 

Investigator Institute Research area Reference 

Ip, C Roswell Park Memorial Mammary cancer prevention by novel CRISP 2002 

Institute selenium compounds 

James, LF Agricultural Research Livestock poisoning from Astragalus CRIS/UDSA 2001 

Service and Oxytropis species 

Johnson, JL University of Nebraska Interaction of trace minerals as FEDRIP 2002 

related to prenatal supplementation of 

the pregnant beef cow 

Kadlubar, F Not available Environmental and genetic CRISP 2002 

epidemiology of colorectal adenomas 

Karagas, M Not available Epidemiology of arsenic and other CRISP 2002 

toxic metals 

Kegley, EB and University of Arkansas Effect of trace mineral level and FEDRIP 2002 

Kellogg, DW source on immune function and 

performance of weaned beef cattle 

Kim, J University of Texas Feasibility study of L-seleno- CRISP 2001 

MD Anderson Cancer methionine in prevention of prostate 

Center cancer 

Kiremidjian- New York University, Dietary selenium and FEDRIP 2002 

Schumacher, L College of Dentistry immunocompetence in the elderly 

et al. 

Klein, EA Cleveland Clinic SELECT: The selenium and vitamin Klein et al. 2000 

Foundation E cancer prevention trial: Rationale 

and design 

Kolonel, LN University of Hawaii at Biomarkers of prostate cancer risk in CRISP 2001 

Manoa a multi-ethnic cohort 

Kolonel, LN University of Hawaii at Epidemiologic studies of diet and CRISP 2001 

Manoa cancer in Hawaii 

Koutnik, V University of Brno Selenium in food chains and its CRIS/UDSA 2001 

impact on human health 

Lacourciere, G National Institutes of Utilization of selenocysteine in FEDRIP 2002 

and Nhlbi, NIH Health selenophosphate biosynthesis 

Lei, X Cornell University Antioxidative role of glutathione CRISP 2001 

peroxidase in transgenic mice 

Lei, XG et al. Cornell University Developing an organic selenium FEDRIP 2002 

supplement for animal nutrition and 

environmental protection 

Lei, XG et al. Cornell University Mineral nutrition in animal agriculture FEDRIP 2002 

and environmental protection 

Lemarchand, L University of Hawaii Phytochemicals and lung risk in a FEDRIP 2002 

multi ethic cohort 

Levander, OA Agricultural Research Role of vitamin E and selenium in CRIS/UDSA 2001 

Service human health promotion 

Levander, OA University of Maryland Kinetics of organic and inorganic CRIS/UDSA 2001 

selenium during dietary 

supplementation 
SELENIUM 213 

3. HEALTH EFFECTS 

Table 3-8. On-going Studies on Selenium Health Effects 

Investigator Institute Research area Reference 

Lewis, NS California Institute of Picosecond dynamic studies of FEDRIP 2002 

Technology electron transfer rates as III-V 

semiconductor/liquid interfaces 

Longnecker, M National Institutes of Validity of toenail element levels as a CRISP 2002 

Health surrogate measure of exposure 

Mahan, DC Ohio State University Mineral and vitamin nutrition of swine FEDRIP 2002 

Mark, S Not available Intervention trials and related studies CRISP 2002 

Marshall, JR University of Arizona Phase II chemprevention trial of CRISP 2002 

selenium and prostate cancer 

May, JM Vanderbilt University Antioxidant interactions of selenium CRISP 2001 

and vitamins C and E 

Medina, D Roswell Park Memorial Selenoproteins in rat mammary CRISP 2001 

Institute tumorigenesis 

Medina, D Roswell Park Memorial Selenium modified gene expression CRISP 2002 

Institute in the carcinogen treated mammary 

gland 

Morgan, DL National Institutes of Toxicity of chemicals used in the FEDRIP 2002 

Health semiconductor industry 

Nomura, AM Kuakini Medical Center Cancer epidemiology of migrant CRISP 2001 

Japanese in Hawaii 

Ogasawara, Y National Institutes of Properties of selenotrisulfides and FEDRIP 2002 

and Nhlbi, NIH Health perselenides 

Page, JG Not available Thirteen week oral toxicity study of CRISP 2002 

1,4-phenylenebis (methylene) 

selenocyanate 

Palmer, IS South Dakota University Biochemistry of selenium FEDRIP 2002 

Pence, BC Texas Technical Induction by selenium of the CRISP 2001 

University Health antioxidant and the prooxidant, 

Sciences Center apoptotic pathways in cultured cells 

Penland, JG Department of Mineral element nutrition, FEDRIP 2002 

Agriculture neuropsuchological function and 

behavior 

Powis, G University of Arizona Thioredoxin reductases and cancer CRISP 2001 

Prolla, TA University of Wisconsin Role of dietary selenium in intestinal CRISP 2001 

tumorigenesis 

Rao, L University of Wisconsin Genetic characterization of the CRISP 2001 

selenoenzyme phospholipidshydroperoxide glutathione peroxidase 

Reddy, BS American Health Chemoprevention of colon cancer by CRISP 2002 

Foundation organoselenium compounds 

Reddy, CC Pennsylvania State Antioxidant effects on prostaglandin CRIS/UDSA 2001 

University metabolism, lipid peroxidation, and 

immunologic defense 
SELENIUM 214 

3. HEALTH EFFECTS 

Table 3-8. On-going Studies on Selenium Health Effects 

Investigator Institute Research area Reference 

Repine, JE Department of Veterans Effect of NAC and/or selenium on FEDRIP 2002 

Affairs blood markers of oxidative stress and 

inflammation 

Roberts, JC University of Utah Advances in selenium CRISP 2002 

supplementation 

Roughead, ZK Department of Biomarkers for assessment of human FEDRIP 2002 

Agriculture mineral nutritional status and 

requirements 

Roy, M New York University Selenium supplementation and CRIS/UDSA 2001 

immunocompetence in the elderly 

Sampliner, RE Department of Veterans Phase III study of the effects of FEDRIP 2002 

Affairs celecoxib, selenium, or the 

combination on adenomatous polyp 

recurrence in adenomatous polyp 

patients 

Sevanian, A University of Southern Oxidant stress and atherogenicity of FEDRIP 2002 

California oxidized LDL 

Shearer, TR Oregon Health & Mechanism of selenium induced FEDRIP 2002 

Science University cataract 

Simoneau, AR Department of Veterans Selenium in prostate cancer FEDRIP 2002 

Affairs 

Smith, AM Ohio State University Influence of gender and life cycle on CRIS/UDSA 2001 

selenium requirements and 

metabolism 

Sordillo, LM Pennsylvania State Oxidant stress and endothelial cell FEDRIP 2002 

University metabolism 

Sordillo, LM Pennsylvania State Mechanisms of endothelia cell FEDRIP 2002 

University dysfunction during selenium 

deficiency 

Stadtman, TC National Institutes of Selenium biochemistry FEDRIP 2002 

and Nhbli, NIH Health 

Stampfer, MJ National Cancer Nutritional and biochemical markers FEDRIP 2002 

Institute of cancer 

Stampfer, MJ Harvard University Prospective study of diet and bladder FEDRIP 2002 

cancer 

Sunde, RA University of Missouri New essential roles for selenium; CRIS/UDSA 2001 

regulatory elements of seleniumdependent peroxidases; regulatory 

elements of the rat glutathione 

peroxidase gene 

Sunde, RA University of Missouri Glutatione peroxidases: Selenium FEDRIP 2002 

requirement and function 

Taylor, JR Department of Veterans Prevention of non-melanoma skin FEDRIP 2002 

Affairs cancer with a nutritional 

supplementation of selenium 

Taylor, EW University of Georgia Selenoproteins, NF-KB, and HIV CRISP 2001 

disease in drug users 
SELENIUM 215 

3. HEALTH EFFECTS 

Table 3-8. On-going Studies on Selenium Health Effects 

Investigator Institute Research area Reference 

Terris, MK Department of Veterans Blood and tissue sampling in prostate FEDRIP 2002 

Affairs ultrasound patients 

Terris, MK Department of Veterans Phase II study of the effect of FEDRIP 2002 

Affairs selenium supplementation on the 

progression of prostate cancer 

Thompson, I University of Texas Biomarkers of risk for prostate cancer CRISP 2001 

Health Science Center 

San Antonio 

Thompson, H Roswell Park Memorial Mechanisms of selenium anticancer CRISP 2001 

Institute and toxic activities 

Thompson, H Roswell Park Memorial Selenium and lung cancer risk CRISP 2002 

Institute 

Turnlund, JR et Department of Influence of dietary intervention on FEDRIP 2002 

al. Agriculture mineral homeostasis 

Turnlund, JR et Department of Trace element metabolism, status FEDRIP 2002 

al. Agriculture and requirements of humans 

Veillon, C Agricultural Research Metabolism, function, and interactions CRIS/UDSA 2001 

Service of selenium using stable isotopes 

Weiss, GR Department of Veterans Pilot study of 1-selenomethionine in FEDRIP 2002 

Affairs prostate cancer patients scheduled to 

undergo radical prostatectomy 

Weiss, SL University of Missouri Molecular basis for selenium CRIS/UDSA 2001 

regulation of glutathione peroxidase 

mRNA 

Whanger, PD Oregon State University Effect of selenium on selenoproteins FEDRIP 2002 

in human muscle and brain cells 

Whanger, PD Oregon State University Metabolic function of selenoprotein CRISP 2001 

Whanger, P Oregon State University Role of selenium and vitamin E in CRIS/UDSA 2001 

scour and immunity of newborn 

calves; influence of pregnancy on 

selenium metabolism in women of 

low selenium status; metabolic 

relationship between selenium and 

myopathy 

Yu, MC University of Southern Singapore cohort study of diet and CRISP 2001 

California cancer 

CRIS = Current Research Information System; CRISP = Computer Retrieval of Information on Science Projects; 

FEDRIP = Federal Research in Progress; NCI = National Cancer Institute; NIH = National Institutes of Health; 

USDA = US Department of Agriculture 

SELENIUM 217 

4. CHEMICAL AND PHYSICAL INFORMATION 

4.1 CHEMICAL IDENTITY 

Information regarding the chemical identity of selenium and selenium compounds is presented in 

Table 4-1. 

4.2 PHYSICAL AND CHEMICAL PROPERTIES 

Selenium is a non-metal element with atomic number 34 and an atomic mass of 78.96 (Lide 2000). 

Selenium belongs to Group 6 (Group VIA) of the periodic table, located between sulfur and tellurium, 

and resembles sulfur both in its various forms and in its compounds. The six stable isotopes of selenium 

are 74Se, 76Se, 77Se, 78Se, 80Se, and 82Se. These isotopes occur naturally with approximate abundances of 

0.87, 9.02, 7.58, 23.52, 49.82, and 9.19%, respectively (Hoffmann and King 1997). Artificial radioactive 

isotopes of selenium have also been created by neutron activation. The gamma-emitting isotope 75Se has 

been used in diagnostic applications of medicine (Hoffmann and King 1997). Selenium exists in several 

allotropic forms. Three are generally recognized, but as many as six have been claimed (Lide 2000). The 

stable form at ordinary room temperatures is the grey or hexagonal form with a melting point of 220.5 EC 

(Lide 2000). The other two important forms are red (monoclinic) with a melting point of 221 EC and 

amorphous selenium, which exists in black and red forms. Black amorphous selenium is vitreous and is 

formed by the rapid cooling of liquid selenium. Red amorphous selenium is colloidal and is formed in 

reduction reactions (Hoffmann and King 1997). Important selenium oxidation states are -2, 0, +4, and +6. 

The chemical properties of selenium are similar to sulfur. Selenium combines with metals and many 

nonmetals directly or in aqueous solution. The selenides resemble sulfides in appearance, composition, 

and properties (Hoffmann and King 1997). Selenium may form halides by reacting vigorously with 

fluorine and chlorine, but the reactions with bromine and iodide are not as rapid. Selenium does not react 

directly with hydrogen fluoride or hydrogen chloride, but decomposes hydrogen iodide to liberate iodine 

and yield hydrogen selenide (Hoffmann and King 1997). Selenium reacts with oxygen to form a number 

of oxides, the most stable of which is selenium dioxide. 

Information regarding the physical and chemical properties of selenium and selenium compounds is 

located in Table 4-2. 
SELENIUM 218 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-1. Chemical Identity of Selenium and Selected Compoundsa 

Hydrogen Selenious 

Characteristic Selenium selenide Selenic acid acid 

Synonyms Elemental 

selenium; 

Dihydrogen 

selenide; 

Selenic acid, 

liquidDOT,b 

Monohydrated 

selenium 

selenium base; hydrogen dioxide; 

selenium dust; selenide [H2Se]; selenous 

colloidal selenium; selenium 

selenium 

homopolymerb

; 

anhydride; 

selenium 

selenium alloy dihydride; 

selenium 

hydride; selane 

Registered trade 

name(s) 

C.I. 77805; 

VANDEXb 

Chemical formula Se H2Se H2SeO4 H2SeO3 

Wisewesser line SE H2 SE H2.SE-04 H2SE-03 

notation 

Identification 

numbers: 

CAS 7782-49-2 7783-07-5 7783-08-6 7783-00-8 

 NIOSH RTECS VS7700000 MX1050000 VS6575000 VS7175000 

 EPA hazardous No data No data No data U204c 

 waste 

 OHM/TADS 

 DOT/UN/NA/IMCO 

7216880 

UN 2658b 

No data 

UN 2202; 

No data 

UN 1905; IMCO 8.0 

No data 

No data 

 shipping Hydrogen 

selenide; 

anhydrous 

HSDB 4493 548 675 6065 

NCI No data No data No data No data 
SELENIUM 219 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-1. Chemical Identity of Selenium and Selected Compoundsa 

Potassium Sodium 

Characteristic Sodium selenate selenate Sodium selenide selenite 

Synonyms Disodium selenate Selenic acid, 

dipotassium saltb 

Disodium 

monoselenideb 

Disodium 

selenite; 

disodium 

selenium 

trioxide; 

selenious 

acid disodium 

salt; sodium 

selenium 

oxide 

Registered trade 

name(s) 

P-40b

; Sel-Tox 

SS02 and SS-20c 

No data No data 

Chemical formula Na2SeO4 

d K2SeO4 Na2Seb

 Na2SeO3 

d 

Wisewesser line NA2 SE-04b KA2 SE-04 NA2 SE NAS SE-03 

notation 

Identification 

numbers: 

CAS 13410-01-0 7790-59-2 1313-85-5b 10102-18-8 

 NIOSH RTECS No data VS6600000 WE0350000b VS7350000 

 EPA hazardous No data No data No data No data 

waste 

 OHM/TADS 

 DOT/UN/NA/IMCO 

No data 

No data 

No data 

No data 

No data 

No data 

7217299 

UN 2630b 

 shipping 

HSDB No data No data No data 768 

NCI No data No data No data No data 
SELENIUM	 220 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-1. Chemical Identity of Selenium and Selected Compoundsa 

Selenium 

Characteristic Selenium dioxide trioxide Selenocystine Selenomethionine 

Synonyms Selenious No data Selenium Methionine, selenob

; 

anhydride; selenium cystineb

; 2-amino-4­

oxide; selenium 3,3-diselenodi- (methylselenyl) 

oxide [SeO2]; DL-alanineb

; butyric acid; 

selenous acid seleno-DL- 2-amino-4-(methylsel 

anhydride cystineb

; DL- eno) 

selenocystineb 

Registered trade No data No data 

name(s) 

Chemical formula SeO2 SeO3

e	 C2H4NO2(CH2)Se (CH3)Se(CH2)2C2H4 

2(CH2)C2 NO2 

H4NO2 

Identification 

numbers: 

CAS 7446-08-04 13768-86-0f 1464-43-3b 1464-42-2 

 NIOSH RTECS VS8575000 No data AY6030000b ES100000 

 EPA hazardous V204c No data No data No data 

 waste 

 OHM/TADS 7800105 No data No data No data 

 DOT/UN/NA/IMCO No data No data No data No data 

 shipping 

HSDB 677 No data No data No data 

NCI No data No data No data No data 
SELENIUM	 221 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-1. Chemical Identity of Selenium and Selected Compoundsa 

Characteristic Selenium sulfide Selenium disulfide 

Synonyms Selenium monosulfide; Selenium disulphide; selenium 

selenium sulfide [SeS]; sulfideb

; sulfur selenide 

selensulfid (German); sulfur 

selenide (SSe) 

Registered trade name(s) No data Exsel; Selsun Blue; Selsumb

; 

Seleen 

Chemical formula SeS SeS2

b 

Wisewesser line notation SE S SE S2b 

Identification numbers: 

CAS 744-34-6 7488-56-4 

 NIOSH RTECS VTO525OOO VS8925000 

EPA hazard waste V205b V205 

 OHM/TADS 8400272 8400272 

 DOT/UN/NA/IMCO shipping No data UN 2657 

HSDB 679 No data 

NCI NCI-C50033 No data 

a

All information obtained from HSDB 2001, except where noted

b

RTECS 2001 

c

EPA 1980a, 1980b (40 CFR 261.33)

d

Budavari et al. 1996 

e

Lide 2000 

f

ChemIDplus 3003 

CAS = Chemical Abstracts Service; DOT/UN/NA/IMCO = Department of Transportation/United Nations/North 

America/International Maritime Dangerous Goods Code; EPA = Environmental Protection Agency; 

HSDB = Hazardous Substances Data Bank; NCI = National Cancer Institute; NIOSH = National Institute for 

Occupational Safety and Health; OHM/TADS = Oil and Hazardous Materials/Technical Assistance Data System; 

RTECS = Registry of Toxic Effects of Chemical Substances 
SELENIUM 222 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of Selenium and Selenium 

Compoundsa
 

Hydrogen 

Property Selenium selenide Selenic acid Selenious acid 

Molecular weight 78.96 80.98 144.97 128.97 

Color/form Red, grey, or black Colorlessb White 

hexagonal 

White hygroscopic 

prismsb 

prisms; 

hygroscopicb 

Physical state Solid Gas Solid Solid 

Melting point 221 EC(red); 

220.5 EC (grey); 

180 EC (black)b 

-65.73 EC 58 EC 70 EC 

(decomposes)b 

Boiling point 685 EC -41.3 EC 260 EC None, loses water 

upon heating 

Density (g/cm3

) 4.39 (red); 4.81 

(grey); 4.28 (black)b 

2.12 (-42 EC) 2.9508 (15 EC) 3.004 (15 EC) 

Odor Unknown; upon Disagreeable odor No data No data 

combustion, smells 

like rotten 

horseradish 

Odor threshold: 

 Water (mg/m3

) No data No data No data No data 

Air No data No data No data No data 

Solubility: Insoluble 377 mL/100 mL at Very soluble in 90 parts dissolve 

 Water 4 EC; hot water in 100 parts of 

270 mL/100 mL at water at 0 EC; 400 

22.5 EC; parts in 100 parts 

0.73 mL/100 mL at 

20 ECc 

at 90 EC 

Organic solvent(s) Insoluble in alcohol, 

slightly soluble in 

Soluble in carbon 

disulfide, carbonyl 

Decomposes in 

alcoholb 

Very soluble in 

alcohol 

carbon disulfide chloride 

(2 mg/100 mL, 

room temperature), 

soluble in ether 

Partion coefficients: 

 Log Kow No data No data No data No data 

 Log Koc No data No data No data No data 

Vapor pressure 1 mmHg at 356 EC 1,330 mmHg at ­ No data 2 mmHg at 15 EC; 

(grey) 30 EC; 3,420 mmHg 4.5 mmHg at 

at 0.2 EC; 9,120 33 EC; 7mmHg at 

mmHg at 30.8 EC 40.3 EC 

Henry’s Law Not applicable No data Not applicable Not applicable 

constant 

Autoignition No data No data No data No data 

temperature 
SELENIUM	 223 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of Selenium and Selenium 

Compoundsa
 

Hydrogen 

Property Selenium selenide Selenic acid Selenious acid
 

Flashpoint No data	 Not applicable No data No data 

Flammability limits No data	 No data No data No data 

Conversion factors No data	 ppm selenium to mg No data No data 

Selenium/m3

 in air 

(20 EC): ppm 

selenium x 3.23=mg 

selenium/m3

 to ppm 

selenium in air 

(20 EC): mg 

selenium/m3

 x 

0.31=ppm selenium 

(v/v) 

Explosive limits Unknownd	 No data No data No data 
SELENIUM	 224 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of Selenium and Selenium 

Compoundsa
 

Potassium Sodium 

Property Sodium selenate selenate selenide Sodium selenite 

Molecular weight	 188.94 221.15 124.94 172.94 

Color/form	 White crystals Colorless crystals or Crystalline; White tetragonal 

white powder	 turns red on crystalsb 

exposure to air 

and 

deliquesces 

Physical state	 Solid Solid Solid Solid 

Melting point	 No data No data >875 EC No data 

Boiling point	 No data No data No data No data 

Density (g/cm3

)	 1.61b 3.07 2.625 (10 EC) No data 

Odor	 No data No data No data No data 

Odor threshold: 

 Water (mg/m3

) No data No data No data No data 

Air No data No data No data No data 

Solubility: 

 Water Very soluble in Soluble in about 1 Decomposes in Freely soluble in 

water part of water water water 

Organic solvent(s) No data No data No data No data 

Partition coefficients: 

 Log Kow No data No data No data No data 

 Log Koc No data No data No data No data 

Vapor pressure No data No data No data No data 

Henry’s Law No data No data No data No data 

constant 

Autoignition No data No data Not flammablee Not flammablee 

temperature 

Flashpoint	 No data No data Not flammablee Not flammablee 

Flammability limits	 No data No data Not flammablee Not flammablee 

Conversion factors	 No data No data No data No data 

Explosive limits	 No data No data No data No data 
SELENIUM	 225 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of Selenium and Selenium 

Compoundsa
 

Selenium 

Property Selenium dioxide trioxide Selenocystine Selenomethionine 

Molecular weight	 110.96 126.96b 334.12c 196.11 

Color/form	 Lustrous, White crystalsb No data Transparent, 

tetragonal needles; hexagonal sheets or 

yellowish-green plates; metallic luster 

vapor or crystals 

Physical state	 Solid Solid No data Solid 

Melting point 340 EC; sublimes at 118 ECb No data DL form: 265 EC 

315 ECb (decomposes); L 

form: 266–268 EC 

Boiling point Noneb Sublimesb No data Not applicable 

Density (g/cm3

)	 3.954 (15 EC) 3.44 b No data No data 

Odor	 Pungent sour smell No data No data No data 

Odor threshold: 

 Water (mg/m3

) 0.0002e No data No data No data 

Air No data No data No data No data 

Solubility: 

Water (g/100 mL) 38.4 at 14 EC; Soluble in water No data No data 

 Organic solvent(s) in methanol: 10.16 No data No data No data 

(parts/100 parts at 11.8 EC; in 93% 

solvent) ethanol: 6.67 at 

14 EC; in acetone: 

4.35 at 15.3 EC; in 

acetic acid: 1.11 at 

13.9 EC; soluble in 

benzene 

Partition coefficients: 

 Log Kow No data No data No data No data 

 Log Koc No data No data No data No data 

Vapor pressure 12.5 mm Hg at No data No data No data 

70 EC; 20.2 mm Hg No data No data 

at 94 EC; 39.0 mm 

Hg at 181 EC; 

760 mm Hg at 

315 EC; 848 mm 

Hg at 320 EC 

Henry’s Law Not applicable Not applicable No data No data 

constant 

Autoignition Not flammablee Not flammablee No data No data 

temperature 

Flashpoint Not flammablee Not flammablee No data No data 
SELENIUM	 226 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of Selenium and Selenium 

Compoundsa
 

Selenium 

Property Selenium dioxide trioxide Selenocystine Selenomethionine 

Flammability limits	 Not flammablee Not flammablee No data No data 

Conversion factors	 ppm (v/v) to mg/m3 No data No data No data 

in air (20 EC): 

ppm (v/v) x 

4.53=mg/m3

; 

mg/m3

 to ppm (v/v) 

in air (20 EC): 

mg/m3

 x 0.22=ppm 

(v/v) 

Explosive limits	 No data No data No data No data 
SELENIUM 227 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of Selenium and Selenium 

Compoundsa
 

Property Selenium sulfide Selenium disulfide 

Molecular weight 111.02f 143.08f 

Color/form Orange-yellow tablets or powderf Bright red-yellow 

powderf 

Physical state Solidf Solidf 

Melting point 118–119 EC (decomposes)f <100 ECf 

Boiling point No data No data 

Density (g/cm3

) 3.056 (0 EC)f No data 

Odor No data No data 

Odor threshold: 

 Water (mg/m3

) No data No data 

Air No data No data 

Solubility: 

 Water Insoluble Insoluble 

 Organic solvent(s) Insoluble in ether; decomposes in alcoholf No data 

Partition coefficients: 

 Log Kow Not applicable No data 

 Log Koc Not applicable No data 

Vapor pressure Not applicable Not applicable 

Henry’s Law constant Not applicable Not applicable 

Autoignition temperature No data No data 

Flashpoint No data No data 

Flammability limits No data No data 

Conversion factors No data No data 

Explosive limits No data No data 

a

All information obtained from Budavari et al. 1996, unless otherwise noted. b

Lide 2000 

c

RTECS 2001 

d

NIOSH/OSHA 1981 

e

Weiss 1986 

f

Lide 1993 

Note: The gray metallic form is the most stable form of selenium (Budavari et al. 1996). 

SELENIUM 229 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

5.1 PRODUCTION 

Selenium is distributed widely in nature and is found in most rocks and soils at concentrations between 

0.1 and 2.0 ppm (Fishbein 1983). However, elemental selenium is seldom found naturally, but it is 

obtained primarily as a byproduct of copper refining (Fishbein 1983). Selenium is contained in the 

constituents of the copper anode that are not solubilized during the copper refining process and ultimately 

accumulate on the bottom of the electrorefining tank. These constituents, usually referred to as slimes, 

contain roughly 5–25% selenium and 2–10% tellurium. Selenium is commercially produced by either 

soda ash roasting or sulfuric acid roasting of the copper slimes. 

Soda Ash Roasting. A soda ash binder is mixed with the slimes and water to form a stiff paste. The 

paste is extruded or pelletized and allowed to dry and then roasted at 530–650 EC. The roasted product is 

then ground and leached into water. The resultant hexavalent selenium dissolves as sodium selenate, 

Na2SeO4. The sodium selenate may be reduced by controlled heating to sodium selenide, which is 

leached with water to form a liver-red solution of sodium selenide that is readily oxidized to the elemental 

form by blowing air through the solution (Hoffmann and King 1997). A second process for the reduction 

of hexavalent selenium involves the use of concentrated hydrochloric acid or ferrous iron salts catalyzed 

by chloride ions as the reductant (Hoffmann and King 1997). 

Sulfuric Acid Roasting. In this method, the copper slimes are mixed with sulfuric acid and roasted at 

500–600 EC to produce selenium dioxide, which volatilizes readily at the roasting temperature. The 

selenium dioxide is reduced to elemental selenium during the scrubbing process with sulfur dioxide and 

water. The resultant commercial-grade selenium can be purified to 99.5–99.7% (Hoffmann and 

King 1997). 

The U.S. production of selenium was 373 and 379 metric tons in 1995 and 1996, respectively (USGS 

2001, 2002). No production data were reported for the years 1997–2001. All of the primary selenium 

producers in the United States are electrolytic copper refiners. Asarco Incorporated and Kennecott Utah 

Copper Corporation produce refined selenium in the United States (Hoffmann and King 1997; SRI 2000). 

Two other copper refiners, Phelps Dodge Corporation and Magma Copper Company, send selenium or 
SELENIUM 230 

5. PRODUCT IMPORT/EXPORT, USE, AND DISPOSAL 

selenium-bearing copper slimes outside of the United States for final processing (Hoffmann and King 

1997). 

Tables 5-1 and 5-2 list facilities in each state that produce, process, or import selenium and selenium 

compounds, respectively, for commercial use. The data do not include facilities such as electric power 

generating plants that release selenium unintentionally as a by-product. The intended use and the range of 

maximum amounts of these substances that are stored on site are also included. The data listed in these 

tables are derived from the Toxics Release Inventory (TRI00 2002). Only certain types of facilities were 

required to report. Therefore, this is not an exhaustive list. 

5.2 IMPORT/EXPORT 

The import volumes of selenium were 324, 428, 346, 339, 326, 452, and 500 metric tons for 1995, 1996, 

1997, 1998, 1999, 2000, and 2001, respectively (USGS 2001, 2002). The U.S. exports of selenium were 

270, 322, 127, 151, 233, 89, and 75 metric tons for 1995, 1996, 1997, 1998, 1999, 2000, and 2001, 

respectively (USGS 2001, 2002). 

5.3 USE 

In electronics, selenium's semiconductor and photoelectric properties make it useful in "electric eyes," 

photographic exposure meters, and rectifiers for home entertainment equipment. In addition, a large 

proportion of the available selenium is used to coat the metal cylinders from which a photographic image 

is transferred in xerography (Fishbein 1983). Selenium is widely used in the glass industry to counter 

coloration that results from iron impurities. It is also used in the production of both red and black glasses 

(Fishbein 1983). Selenium is contained in pigments that are used in plastics, paints, enamels, inks, and 

rubber (Fishbein 1983). Selenium is used as a catalyst in the preparation of pharmaceuticals including 

niacin and cortisone, as an ingredient in antidandruff shampoos (selenium sulfide), and as a constituent of 

fungicides (selenium sulfide) (IARC 1975a). Radioactive selenium is used in diagnostic medicine and 

aids in the visualization of difficult-to-study malignant tumors (Fishbein 1983; Jereb et al. 1975). 

Selenium is contained in some dietary supplements at concentrations in the range of 10–25 μg/tablet 

(Goodman et al. 1990). Selenium is also used as a nutritional feed additive for poultry and livestock, in 

pesticide formulations, and as an accelerator and vulcanizing agent in rubber production (Fishbein 1983; 

NAS 1976a). Table 5-3 lists some specific uses of selected selenium compounds. 
SELENIUM 231 

5. PRODUCT IMPORT/EXPORT, USE, AND DISPOSAL 

Table 5-1. Facilities that Produce, Process, or Use Selenium 

Number of Minimum amount Maximum amount on 

Statea facilities on site in poundsb site in poundsb Activities and usesc 

AZ 1 1,000 9,999 12 

CA 2 100 99,999 12 

IA 1 100 999 7 

IL 1 1,000 9,999 7 

IN 2 100,000 999,999 8 

LA 1 1,000 9,999 12 

MI 1 0 99 12 

OK 1 100 999 1, 5 

OR 1 100,000 999,999 12 

PA 2 10,000 99,999 6, 8 

SC 1 10,000 99,999 1, 3, 4, 5, 9, 12, 13 

WA 1 100 999 14 

WY 1 0 99 1, 13 

Source: TRI00 2002 

a

Post office state abbreviations used 

b

Amounts on site reported by facilities in each state 

c

Activities/Uses: 

1. Produce 6. Impurity 11. Chemical Processing Aid 

2. Import 7. Reactant 12. Manufacturing Aid 

3. Onsite use/processing 8. Formulation Component 13. Ancillary/Other Uses 

4. Sale/Distribution 9. Article Component 14. Process Impurity 

5. Byproduct 10. Repackaging 
SELENIUM 232 

5. PRODUCT IMPORT/EXPORT, USE, AND DISPOSAL 

Table 5-2. Facilities that Produce, Process, or Use Selenium Compounds 

Number of Minimum amount Maximum amount 

Statea facilities on site in poundsb on site in poundsb Activities and usesc 

AL 4 100 99,999 1, 3, 4, 5, 8, 9, 12, 13 

AR 1 10,000 99,999 12 

AZ 2 10,000 999,999 1, 3, 4, 5, 9, 13, 14 

CA 1 10,000 99,999 8, 9 

FL 1 1,000 9,999 1, 5, 9, 12, 13, 14 

GA 5 1,000 99,999 1, 2, 3, 4, 5, 6, 9, 13 

IA 2 100 9,999 3, 4, 7, 8 

ID 1 100,000 999,999 1, 5 

IL 3 1,000 99,999 1, 5, 7, 12, 13 

IN 4 0 99,999 1, 5, 7, 9, 12, 13 

KY 5 100 99,999 1, 3, 4, 5, 9, 12, 13 

LA 1 10,000 99,999 1, 3, 4, 5, 6, 8 

MA 1 10,000 99,999 1, 5 

MD 2 1,000 99,999 1, 3, 4, 5, 6, 13 

MI 4 1,000 999,999 1, 2, 3, 4, 5, 8, 9, 12, 13 

MN 1 1,000 9,999 1, 2, 9, 13, 14 

MO 1 10,000 99,999 7 

MT 1 10,000 99,999 1, 5, 12, 14 

NC 3 10,000 99,999 1, 3, 4, 5, 9, 12, 13, 14 

NM 4 0 99,999 1, 3, 4, 5, 9, 12, 13 

NV 6 10,000 9,999,999 1, 5, 6, 10, 13, 14 

OH 8 1,000 9,999,999 1, 3, 4, 5, 7, 9, 12, 13, 14 

OK 1 1,000 9,999 8 

PA 8 0 999,999 1, 4, 5, 6, 9, 12, 13, 14 

SC 1 10,000 99,999 1, 3, 4, 5, 9, 12, 13 

TN 2 1,000 99,999 1, 5 

TX 10 10,000 999,999 1, 2, 3, 4, 5, 6, 8, 9, 12, 14 

UT 4 10,000 9,999,999 1, 3, 4, 5, 6, 9, 12, 13 

VA 1 10,000 99,999 1, 5 

WV 9 100 99,999 1, 3, 4, 5, 9, 12, 13, 14 

WY 2 0 99,999 1, 4, 5, 9, 12, 13 

Source: TRI00 2002 

a

Post office state abbreviations used 

b

Amounts on site reported by facilities in each state 

c

Activities/Uses: 

1. Produce 6. Impurity 11. Chemical Processing Aid 

2. Import 7. Reactant 12. Manufacturing Aid 

3. Onsite use/processing 8. Formulation Component 13. Ancillary/Other Uses 

4. Sale/Distribution 9. Article Component 14. Process Impurity 

5. Byproduct 10. Repackaging 
SELENIUM 233 

5. PRODUCT IMPORT/EXPORT, USE, AND DISPOSAL 

Table 5-3. Some Selenium Compounds and Their Usesa 

Compound Use 

Elemental selenium In rectifiers, photoelectric cells, blasting caps, xerography, stainless 

steel; as a dehydrogenation-catalyst 

Sodium selenate As an insecticide; in glass manufacture; in medicinals to control animal 

(Na2SeO4) diseases 

Sodium selenite In glass manufacture; as a soil additive for selenium-deficient areas 

(Na2SeO3) 

Selenium diethyldithio- Fungicide; vulcanizing agent 

carbamate 

Selenium disulfide In veterinary medicine 

(SeS2) 

Selenium sulfide In anti-dandruff shampoos and in veterinary medicine 

(SeS) 

Selenium dioxide Catalyst for oxidation, hydrogenation, or dehydrogenation of organic 

(SeO2) compounds 

Selenium hexafluoride As a gaseous electric insulator 

(SeF6) 

Selenium oxychloride Solvent for sulfur, selenium, tellurium, rubber, bakelite, gums, resins, 

(SeOCl2) glue, asphalt, and other materials 

Aluminum selenide Preparation of hydrogen selenide for semi-conductors 

(Al2Se3) 

Ammonium selenite Manufacture of red glass 

[(NH4)2SeO3] 

Cadmium selenide Photoconductors, photoelectric cells, rectifiers 

Cupric selenate In coloring copper and copper alloys 

(CuSeO4) 

Tungsten diselenide In lubricants 

(WSe2) 

a

Adapted from Fishbein 1983 
SELENIUM 234 

5. PRODUCT IMPORT/EXPORT, USE, AND DISPOSAL 

The 2002 consumption patterns for selenium by industry were as follows: glass manufacturing, 35%; 

chemicals and pigments, 20%; electronics, 12%; and miscellaneous (including agriculture and 

metallurgy), 33% (USGS 2002). 

5.4 DISPOSAL 

Selenium was listed by EPA in 1973 as a nonradioactive hazardous element and, as such, is subject to 

many regulations (Dawson and Mercer 1986). Selenium compounds should be stored in a dry area to 

avoid contamination of water with selenium and to decrease the hazards that may result from human 

exposure to selenium-contaminated water (ITII 1976). 

Disposal and waste treatment consist of treating an acidified solution of selenium with sodium sulfite to 

form the reducing agent sulfur dioxide. The selenium solution is then heated to produce elemental 

selenium, which is less mobile in the environment and less bioavailable, and the solution is filtered and 

washed (ITII 1976). 

According to the TRI, in 2000, an estimated 76,248 pounds of elemental selenium and 1,782,654 pounds 

of selenium compounds were transferred off-site, presumably for disposal (TRI00 2002). 
SELENIUM 235 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.1 OVERVIEW 

Selenium has been identified in at least 508 of the 1,623 hazardous waste sites that have been proposed 

for inclusion on the EPA National Priorities List (NPL) (HazDat 2003). However, the number of sites 

evaluated for selenium is not known. The frequency of these sites can be seen in Figure 6-1. Of these 

sites, 502 are located within the United States, 4 are located in the Commonwealth of Puerto Rico, 1 is 

located in Guam, and 1 is located in the U.S. Virgin Islands (not shown). 

Selenium is ubiquitous in the environment, being released from both natural and anthropogenic sources. 

The principal releases of selenium into the environment as a consequence of human activities result from 

the combustion of coal. Workers in the metals industry and health services, mechanics, and painters may 

be exposed to higher levels of selenium than the general population or persons employed in other trades. 

For the general population, the primary exposure pathways, in order of decreasing relative proportions, 

are food, water, and air. The relative proportions of these exposure pathways at hazardous waste sites are 

not known. Although selenium has been reported at hazardous waste sites, analysis on specific forms has 

not been performed. In air, selenium dioxide, methyl selenide, and dimethyl selenide are the most 

prevalent forms found in the atmosphere. Selenates and selenites are water soluble and, thus, can be 

found in water sources. Salts of selenic and selenious acids are most likely to be found in surface water 

and water contained in soil. Selenium sulfides would not be expected to be found at most hazardous 

waste sites, since they are usually manufactured for use in shampoos. Natural sources of selenium 

include the weathering of selenium-containing rocks to soils and volcanic eruptions. 

The primary factor determining the fate of selenium in the environment is its oxidation state. Selenium is 

stable in four valence states (-2, 0, +4, and +6) and forms chemical compounds similar to those of sulfur. 

The heavy metal selenides (-2) are insoluble in water, as is elemental selenium. The inorganic alkali 

selenites (+4) and selenates (+6) are soluble in water (Weast 1988) and are therefore more bioavailable. 

Conditions such as pH (negative log hydrogen ion concentration), Eh (oxidation-reduction potential), and 

the presence of metal oxides affect the partitioning of the various compounds of selenium in the 

environment. In general, elemental selenium is stable in soils and is found at low levels in water because 

of its ability to coprecipitate with sediments. The soluble selenates are readily taken up by plants and 
1-3 

4-6 

7-9 

10-21 

22-31 

45 

Freq u en cy of

NPL Sites 

Derived from HazDat 2003 

SELENIUM 236 

6. POTENTIAL FOR HUMAN EXPOSURE 

Figure 6-1. Frequency of NPL Sites with Selenium Contamination 
SELENIUM 237 

6. POTENTIAL FOR HUMAN EXPOSURE 

converted to organic compounds such as selenomethionine, selenocysteine, dimethyl selenide, and 

dimethyl diselenide. Selenium is bioaccumulated by aquatic organisms and may also biomagnify in 

aquatic organisms. 

6.2 RELEASES TO THE ENVIRONMENT 

The greatest proportion of selenium released to the environment as a consequence of regulated human 

activities is in coal fly ash, resulting from coal combustion. Anthropogenic emission sources of 

atmospheric selenium include coal and oil combustion facilities, selenium refining factories, base metal 

smelting and refining factories, mining and milling operations, and end-product manufacturers (e.g., some 

semiconductor manufacturers). Natural atmospheric releases of selenium result from volatilization of 

selenium by plants and bacteria, and from volcanic activity. Some selenium is released to water via 

sewage effluent, agricultural runoff, and industrial waste water. Selenium is released to soil primarily by 

leaching and weathering of the parent bedrock material, although dry and wet deposition also contribute 

to soil selenium levels. 

According to the Superfund Amendments and Reauthorization Act (SARA), Section 313, Toxic Release 

Inventory (TRI00 2002), an estimated total of 264,267 pounds of elemental selenium was released to air, 

water, land, or injected underground from manufacturing and processing facilities in the United States in 

2000 (see Table 6-1). In addition, 7,870,609 pounds of selenium compounds were released to air, water, 

land, or injected underground in 2000 (see Table 6-2). These data include all facilities that manufacture, 

import, and process selenium and selenium compounds as well as facilities (electric generating facilities, 

petroleum facilities, etc.) with unintentional releases to the environment. The TRI data should be used 

with caution because only certain types of facilities are required to report. This is not an exhaustive list. 

6.2.1 Air 

Combustion of coal and other fossil fuels is the primary source of airborne selenium compounds. In air, 

elemental selenium burns to form selenium dioxide; however, during the combustion of fossil fuels, 

essentially all of the selenium dioxide produced should be reduced to elemental selenium by the sulfur 

dioxide that results from the combustion of these materials (NAS 1976a). Estimates of the quantity of 

selenium released to the air from fossil fuel combustion vary. Estimated annual selenium air emissions 
SELENIUM 238 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-1. Releases to the Environment from Facilities that Produce, Process, or 

Use Selenium
 

Reported amounts released in pounds per yeara 

Number Under- Total on- Total off- Total on and 

Stateb 

of 

facilities Airc Water 

ground 

injection Land 

site 

released 

site 

releasee 

off-site 

release 

AZ 1 No data No data No data No data No data 71,747 71,747 

CA 2 1 0 No data 35,848 35,849 10 35,859 

IA 1 No data No data No data 27 27 339 366 

IL 3 109 19 No data 1 129 231 360 

IN 3 0 No data No data 2,260 2,260 2,056 4,316 

LA 2 No data No data 40,246 No data 40,246 No data 40,246 

MI 1 5 No data No data No data 5 5 10 

OK 1 No data 250 No data 250 500 No data 500 

OR 1 0 No data No data 112,600 112,600 1 112,601 

PA 2 61,437 750 No data No data 62,187 1,857 64,044 

SC 1 3,929 No data No data 6,533 10,462 No data 10,462 

WA 1 No data No data No data 2 2 2 4 

WY 1 No data No data No data No data No data 0 0 

Total 25 65,481 1,019 40,246 157,521 264,267 76,248 340,515 

Source: TRI00 2002 

a

Data in TRI are maximum amounts released by each facility.

b

Post office state abbreviations are used. 

c

The sum of fugitive and stack releases are included in releases to air by a given facility.

d

The sum of all releases of the chemical to air, land, water, and underground injection wells. 

e

Total amount of chemical transferred off-site, including to publicly owned treatment works (POTW).
 
SELENIUM 239 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-2. Releases to the Environment from Facilities that Produce, Process, or 

Use Selenium Compounds
 

Reported amounts released in pounds per yeara 

Number Under- Total on- Total off- Total on and 

Stateb 

of 

facilities Airc Water 

ground 

injection Land 

site 

released 

site 

releasee 

off-site 

release 

AL 4 15,545 4,125 No data 33,253 52,923 1,069 53,992 

AR 1 546 No data No data No data 546 7,493 8,039 

AZ 2 505 0 No data 820,005 820,510 2,265 822,775 

CA 1 5 No data No data No data 5 No data 5 

FL 2 7,105 No data No data 362 7,467 3 7,470 

GA 6 72,273 1,037 No data 43,067 116,377 10 116,387 

IA 5 No data No data No data No data No data No data 0 

ID 1 1,849 No data No data 98,184 100,033 5 100,038 

IL 7 56 No data No data 0 56 81,940 81,996 

IN 5 4,427 1,871 No data 9,665 15,963 7,739 23,702 

KY 5 19,750 14,200 No data 41,051 75,001 No data 75,001 

LA 1 192 0 No data No data 192 45,241 45,433 

MA 1 234 100 No data 580 914 7,440 8,354 

MD 2 16,001 360 No data 720 17,081 1,262 18,343 

MI 4 16,408 2,417 No data 2,758,596 2,777,421 897,981 3,675,402 

MN 2 255 2,400 No data No data 2,655 265 2,920 

MO 2 250 No data No data No data 250 250 500 

MT 1 250 0 No data 13,000 13,250 250 13,500 

NC 4 56,017 1,092 No data 27,080 84,189 10 84,199 

NM 4 1,056 0 No data 91,282 92,338 24,300 116,638 

NV 6 2,400 40 0 1,174,514 1,176,954 0 1,176,954 

OH 9 71,941 16,635 No data 74,622 163,198 46,858 210,056 

OK 1 9,000 No data No data No data 9,000 50 9,050 

PA 8 39,509 2,093 No data 23,500 65,102 40,199 105,301 

SC 1 4,174 No data No data 11,605 15,779 No data 15,779 

TN 2 14,010 4,600 No data 21,550 40,160 5 40,165 
SELENIUM 240 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-2. Releases to the Environment from Facilities that Produce, Process, or 

Use Selenium Compounds
 

Reported amounts released in pounds per yeara 

Number Under- Total on- Total off- Total on and 

Stateb 

of 

facilities Airc Water 

ground 

injection Land 

site 

released 

site 

releasee 

off-site 

release 

TX 12 131,637 22 27,699 197,164 356,522 609,353 965,875 

UT 4 4,122 1,000 No data 1,635,235 1,640,357 263 1,640,620 

VA 1 4,100 600 No data 14,000 18,700 No data 18,700 

WV 9 72,843 3,456 No data 93,928 170,227 8,403 178,630 

WY 2 10,469 No data No data 26,970 37,439 No data 37,439 

Total 119 576,929 56,048 27,699 7,209,933 7,870,609 1,782,654 9,653,263 

Source: TRI00 2002 

a

Data in TRI are maximum amounts released by each facility.

b

Post office state abbreviations are used. 

c

The sum of fugitive and stack releases are included in releases to air by a given facility.

d

The sum of all releases of the chemical to air, land, water, and underground injection wells. 

e

Total amount of chemical transferred off-site, including to publicly owned treatment works (POTW).
 
SELENIUM 241 

6. POTENTIAL FOR HUMAN EXPOSURE 

from stationary sources in the United States for 1969–1971, 1978, and 1983 were 900, 1,240, and 

1,560 tons selenium/year, respectively (EPA 1974; Lee and Duffield 1979). Dulka and Risby (1976) 

estimated yearly releases of selenium to the air from fossil fuel combustion to be 1,000 tons. Harr (1978) 

estimated that 1,500 tons were released annually, with additional air releases from industrial and 

municipal wastes totaling 2,700 tons and 360 tons, respectively. Selenium releases to the air are likely to 

increase as more coal is burned in the future. The estimated selenium emissions from Canadian nonferrous smelters (stack plus fugitive) were 3.02 tons in 1993 (Skeaff and Dubreuil 1997). 

Incineration of rubber tires, paper, and municipal waste is an additional source of atmospheric selenium. 

Hashimoto et al. (1970) reported selenium concentrations in rubber tires to be 1.3 mg/kg. Seventy 

different kinds of paper have been found to contain selenium (West 1967). Combustion of municipal 

solid waste results in stack emissions ranging from 0.00098 to 0.00216 pounds (0.44–0.98 g) of selenium 

per ton of refuse (Johnson 1970). 

The amount of selenium contributed to the air by other sources is not known. Microbial action within the 

soil may also contribute selenium to the air (Fishbein 1983). Selenium biomethylation volatilizes about 

3,000 tons of selenium per year into the atmosphere, which eventually returns to earth in rainfall (NAS 

1976a). Volcanic gas is suspected to be the major natural source of atmospheric selenium. Certain plants 

metabolize inorganic selenium compounds to volatile selenium in the forms of dimethyl selenide (Lewis 

et al. 1971) and dimethyl diselenide (Evans et al. 1968). Animals are also capable of volatilizing 

selenium and releasing dimethyl selenide in expired air (Schultz and Lewis 1940). 

Fly ash settling ponds (which contain high concentrations of selenium) and hazardous waste sites where 

selenium compounds were disposed of in the past are potential sources of atmospheric selenium through 

fugitive dust emissions. Selenium emissions from these potential sources have not been quantified. 

According to TRI, an estimated total of at least 65,481 pounds of elemental selenium and 576,929 pounds 

of selenium compounds were discharged to the air from manufacturing and processing facilities in the 

United States in 2000 (TRI00 2002) (see Tables 6-1 and 6-2). The data listed in the TRI tables should be 

used with caution since only certain types of facilities are required to report. This is not an exhaustive 

list. 

Selenium has been identified in air at 13 of the 508 NPL hazardous waste sites where it was detected in 

some environmental media (HazDat 2003). 
SELENIUM 242 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.2.2 Water 

Surface waters can receive selenium from the atmosphere by dry and wet deposition, from adjoining 

waters that may contain selenium, from surface runoff, and from subsurface drainage. Sewage treatment 

plants are another source of selenium releases to water. Effluents from sewage treatment plants and oil 

refineries appear to be the major sources of selenium in the San Francisco estuarine system (Cutter 1989). 

In a study of direct discharges from oil refineries in San Francisco Bay, the average selenium 

concentration in the effluent was 0.067 mg/L with a range of 0.0066–0.156 mg/L (Barceloux 1999; Cutter 

1989). Approximately 50–76% of the total selenium in the effluents was selenite. This proportion of 

selenite is higher than that found in natural estuary sources in the San Francisco Bay (Cutter 1989). 

About 150,000–460,000 tons of selenium per year are deposited in coal fly ash (Andren and Klein 1975; 

Doran 1982). Selenium from fly ash settling ponds and hazardous waste sites could reach surface water 

via runoff or could reach groundwater via leaching. Concentrations of 0.10–0.25 mg/L in a settling basin 

effluent from coal fly ash in North Carolina were reported by Lemly (1985). Overflow from the ash basin 

of a coal fired electric generating facility to Belews Lake resulted in surface water selenium 

concentrations of 0.005–0.020 mg/L in the lake basin. These levels have been reduced considerably since 

1986 when the discharge of selenium laden waste water to the lake was discontinued. The peak selenium 

concentration in 1996 was <0.001 mg/L (Lemly 1997). Selenium concentrations as high as 0.28 mg/L 

have been reported for raw sewage, 0.045 mg/L for primary effluent, and 0.050 mg/L for secondary 

effluent (Baird et al. 1972). Irrigation drainage from seleniferous soils can increase selenium 

concentrations in surface water and has resulted in levels that are toxic to wildfowl at Kesterson National 

Wildlife Refuge in California (Ohlendorf et al. 1986a, 1988). Selenium was found to be released during 

coal mining because of the oxidation of selenium-bearing pyrite (Dreher and Finkelman 1992). 

According to the TRI, an estimated total of 1,019 pounds of elemental selenium and 56,048 pounds of 

selenium compounds were discharged to surface water from manufacturing and processing facilities in 

the United States in 2000 (see Tables 6-1 and 6-2). The data listed in the TRI tables should be used with 

caution since only certain types of facilities are required to report. This is not an exhaustive list. 

Selenium has been identified in groundwater at 271 sites and surface water at 106 sites of the 508 NPL 

hazardous waste sites where it was detected in some environmental media (HazDat 2003). 
SELENIUM 243 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.2.3 Soil 

The primary factor that controls selenium concentrations in soil is the selenium content of the parent 

bedrock materials that release selenium via weathering processes and leaching (NAS 1976a). Natural 

weathering processes are thought to release about 100,000–200,000 metric tons of selenium per year 

(Andren and Klein 1975). Atmospheric deposition of selenium also contributes to selenium in the soil. 

In the past, selenium was used in pesticide products, but because of its stability in soils and subsequent 

contamination of food crops, its use in pesticide products is now restricted. The release of selenium to 

soil from fly ash settling ponds and hazardous waste sites has not been quantified. 

According to the TRI, an estimated total of 157,521 pounds of elemental selenium and 7,209,933 pounds 

of selenium compounds were discharged to land from manufacturing and processing facilities in the 

United States in 2000 (TRI00 2002). In addition, 40,246 pounds of selenium and 27,699 pounds of 

selenium compounds were injected underground (see Table 6-2). The data listed in the TRI tables should 

be used with caution since only certain types of facilities are required to report. This is not an exhaustive 

list. 

Selenium has been identified in soil at 188 sites and sediment at 113 of the 508 NPL hazardous waste 

sites where it was detected in some environmental media (HazDat 2003). 

6.3 ENVIRONMENTAL FATE 

The behavior of selenium in the environment is influenced to a large degree by its oxidation state and the 

consequent differences in the behavior of its different chemical compounds (EPA 1979c; NAS 1976a). 

The oxidation state of selenium in the environment is dependent on ambient conditions, particularly on 

pH, pE, and biological activity (Maier et al. 1988). 

6.3.1 Transport and Partitioning 

The volatile selenium compounds that partition into the atmosphere include the inorganic compounds, 

selenium dioxide and hydrogen selenide, and the organic compounds, dimethyl selenide and dimethyl 

diselenide. Hydrogen selenide is highly reactive in air and is rapidly oxidized to elemental selenium and 

water (NAS 1976a), but the other compounds can persist in air. 
SELENIUM 244 

6. POTENTIAL FOR HUMAN EXPOSURE 

Selenium compounds released to the atmosphere can be removed by dry or wet deposition to soils or to 

surface water. The annual wet deposition rate of selenium at two rural/agricultural sites in Queenstown, 

Maryland and St. Mary’s, Maryland were 287 and 140 μg/m2

-year, respectively (Scudlark et al. 1994). 

Selenium concentrations ranging from 0.04 to 1.4 μg/L have been detected in rain and snow (Hashimoto 

and Winchester 1967). Kubota and coworkers (1975) reported selenium concentrations of 0.02– 

0.37 μg/L in rainwater at several locations in the United States and Denmark. Selenium was detected at 

average concentrations of 5.60–7.86 μg/L during four rainfall events in Riyadh, Saudi Arabia 

(Alabdula’aly and Khan 2000). 

The forms of selenium expected to be found in surface water and the water contained in soils are the salts 

of selenic and selenious acids. Selenic acid (H2SeO4) is a strong acid. The soluble selenate salts of this 

acid are expected to occur in alkaline waters. Sodium selenate is one of the most mobile selenium 

compounds in the environment because of its high solubility and inability to adsorb onto soil particles 

(NAS 1976a). Selenious acid (H2SeO3) is a weak acid, and the diselenite ion predominates in waters 

between pH 3.5 and 9. Most selenites are less soluble in water than the corresponding selenates (NAS 

1980b). 

Selenium in an aquatic environment is bioaccumulated by aquatic organisms (Chau and Riley 1965; 

Ohlendorf et al. 1986a; Rudd and Turner 1983a; Saiki and Lowe 1987). Lemly (1985) has reported 

bioconcentration factors (BCFs) of 150–1,850 and bioaccumulation factors (BAFs) of 1,746–3,975 for 

selenium in freshwater. In the Kesterson National Wildlife Refuge in the San Joaquin Valley of 

California, elevated levels of selenium have been measured (dry weight) in algae (average 35 mg/kg), 

midge larvae (139 mg/kg), dragonfly and damselfly nymphs (average 122 and 175 mg/kg, respectively), 

and mosquito fish (170 mg/kg) (Ohlendorf et al. 1986b). For comparison, the mean concentrations of 

selenium found in fish throughout the United States in the 1976–1977, 1978–1979, and 1980–1981 

National Pesticide Monitoring Program were 0.56, 0.46, and 0.47 mg/kg wet weight, respectively (Lowe 

et al. 1985; May and McKinney 1981; Ohlendorf et al. 1986b). Similarly, Lemly (1985) found elevated 

selenium concentrations in aquatic organisms living in a power plant cooling reservoir in North Carolina. 

The degree of bioaccumulation of selenium exhibited a stable pattern over several years, with selenium 

concentrations (wet weight) as follows: fish (6–35 mg/kg) > benthic insects (12–15 mg/kg) > annelids 

(10–12 mg/kg) > molluscs and crustaceans (5–9 mg/kg) > periphyton (4–6 mg/kg) (Ohlendorf et al. 

1986a). In fish, selenium was concentrated in visceral tissue (25–35 mg/kg wet weight) more than in 

skeletal muscle (6–11 mg/kg wet weight). Adams (1976) reported BCFs of 62.1, 14.3, 6.3, 3.2, and 
SELENIUM 245 

6. POTENTIAL FOR HUMAN EXPOSURE 

10.5 for selenium in the viscera, gill, head and tail, muscle, and whole trout, respectively. The BCFs and 

BAFs for selenium in visceral tissue (i.e., heart, hepatopancreas, spleen, and gonads) of fish have been 

estimated to range from 35 to 1,850 and from 1,058 to 3,980, respectively (Lemly 1982, 1985). Lemly 

(1985) also estimated BAFs for selenium in skeletal muscle of fish to range from 485 to 1,746, depending 

on the species. Maier et al. (1988) estimated selenium BAFs for algae to range from 100 to 2,600, and 

Besser et al. (1993) estimated BCFs of 16,000 for algae, 200,000 for daphnids, and 5,000 for bluegills 

from exposures to 1 μg/L selenomethionine. Selenite was more concentrated than selenate for algae and 

daphnids, whereas bluegills concentrated both inorganic species about equally (Besser et al. 1993). 

Selenium accumulation from selenomethionine occurred more readily than from selenite or selenate 

(Besser et al. 1989). 

Some evidence indicates that selenium might biomagnify in aquatic organisms under natural conditions 

(Lemly 1985; Maier et al. 1988; NCDNR 1986; Sandholm et al. 1973). Biomagnification is evidenced by 

progressively higher concentrations of an element or substance in organisms at successively higher 

trophic levels. More than 50% of the selenium contained in sediments in the ponds and the reservoir in 

the Kesterson National Wildlife Refuge in California occurs in organic forms (Maier et al. 1988), 

resulting from the synthesis and bioaccumulation of organic selenium before the plants die and decay on 

the bottom. 

In soils, pH and Eh are determining factors in the transport and partitioning of selenium. Elemental 

selenium is essentially insoluble and may represent a major inert "sink" for selenium introduced into the 

environment under anaerobic conditions (NAS 1976b). Heavy metal selenides and selenium sulfides, 

which are also insoluble, predominate in acidic (low pH) soils and in soils with high amounts of organic 

matter. Selenium in this form is immobile and will remain in the soil. The selenides of other metals such 

as copper and cadmium are of low solubility (NAS 1976b). Sodium and potassium selenites dominate in 

neutral, well-drained mineral soils, where some soluble metal selenites may be found as well. In alkaline 

(pH>7.5), well-oxidized soil environments, selenates are the major selenium species. Because of their 

high solubility and low tendency to adsorb onto soil particles, the selenates are very mobile (KabatasPendias and Pendias 1984) and are readily taken up by biological systems (Klaassen et al. 1986) or 

leached through the soil. Gerritse et al. (1982) found selenium to be very mobile in sewage sludge 

leachate. They reported Kd values (distribution coefficient = [concentration of selenium sorbed on soil or 

rock]/[concentration of selenium in solution]) of 14.9 mL/g for sandy loam and 5.91 mL/g for sludgetreated sandy soils. Selenite forms stable ferric oxide-selenite adsorption complexes in acid or neutral 

soils (Geering et al. 1968). 
SELENIUM 246 

6. POTENTIAL FOR HUMAN EXPOSURE 

When environments favor the soluble forms of selenium (alkaline and oxidizing conditions), these forms 

can be accumulated by plants. In addition, although both selenite (Se4+) and selenate (Se6+) are soluble 

forms of selenium, selenate was found to be the preferred form of selenium taken up by plants (Baňuelos 

and Meek 1990). Preferential uptake of selenate may be caused by its tendency to be less strongly 

adsorbed to soil particles and organic matter than selenite (Baňuelos and Meek 1990). Selenium uptake 

by plants is influenced by many factors including soil type, pH, colloidal content, concentration of 

organic material, oxidation-reduction potentials in the root-soil environment, and total level of selenium 

in the soil (Fishbein 1983; Robberecht et al. 1982). In acidic soils (pH 4.5–6.5) and under high moisture 

conditions, selenium is in the form of selenite and is bound to colloids as iron hydroxide selenium 

complexes. These complexes are insoluble and generally not bioavailable to plants (Galgan and Frank 

1995). In basic soils (pH 7.5–8.5), selenium is present as soluble selenate. Soluble selenates (principally 

sodium selenate) appear to be responsible for most of the naturally occurring accumulation of high levels 

of selenium by plants, although much of the total selenium in soil may be present in other forms (NAS 

1976a). The use of lime and plant ash as fertilizers, which would raise the pH of the soil and favor the 

formation of selenate, has been implicated as a contributing factor in the accumulation of selenium in 

crops grown in high selenium soil found in certain regions of China (Yang et al. 1988). 

6.3.2 Transformation and Degradation 

6.3.2.1 Air 

Selenium dioxide released to the air from the combustion of fossil fuels should be largely reduced to 

elemental selenium by sulfur dioxide formed during the combustion (NAS 1976b). During a 1991 study, 

Oehm et al. found that selenium dioxide reacting with atmospheric moisture generates selenious acid 

aerosols. Hydrogen selenide is unstable in air and is oxidized to elemental selenium and water (NAS 

1976a). Hazards from hydrogen selenide are expected, therefore, to be confined to occupational settings 

where the confined gas might build up to hazardous levels despite oxidative losses (NAS 1976a). 

Dimethyl selenide and methyl selenide are volatile organic compounds that can partition into and persist 

in the atmosphere. Other selenium compounds released to the atmosphere as dust can be removed by wet 

deposition (in rain or snow) or by dry deposition. 
SELENIUM 247 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.3.2.2 Water 

In general, the more soluble and mobile forms of selenium (e.g., selenite and selenate) dominate under 

aerobic (high oxygen concentrations) and alkaline (high pH) conditions (NAS 1976a; Shamberger 1981). 

Selenates have been predicted thermodynamically to predominate under aerobic conditions, but a review 

of the literature indicates that both selenites and selenates are equally common in surface waters 

(Robberecht and Van Grieken 1982). For selenites in solution, equilibria will be set up between H2SeO3, 

HSeO3

-

, SeO3

-

, HSe2O5

-

, and Se2O5

2-. The relative concentrations of these species will be determined by 

the pH of the solution and the total concentration of the electrolytes. Between pH 3.5 and 9, dissolved 

selenite would be expected to be present predominantly as the diselenite ion, whereas dissolved selenate 

would occur predominantly as SeO4

2 -. Sodium predominates as the counter ion of selenate and selenite in 

most surface waters. 

A study completed by Bender et al. (1991) using a simulated laboratory pond found that bacteria and 

cyanobacteria have two possible mechanisms for the uptake and transformation of selenate. The uptake 

mechanism involves the reduction of selenate to elemental selenium that will be physically held within 

the biological mat. The microorganisms were also found to cause the transformation of soluble selenium 

into volatile alkyl selenium compounds (Bender et al. 1991). 

In some deep aquifers, selenium transport in groundwater was found to be strongly retarded (White et al. 

1991). This phenomena is thought to be caused by chemical reduction and precipitation mediated by 

microbial activity. 

Under acidic conditions, selenite can be rapidly reduced to elemental selenium by mild reducing agents 

such as ascorbic acid or sulfur dioxide (NAS 1980b). Selenate can be converted to selenite or elemental 

selenium in aquatic systems, but this reaction is slow relative to other transformations. Once formed, 

elemental selenium is stable over a wide range of pH values and a range of mildly oxidizing to reducing 

conditions. The formation of various metal selenides is favored by acidic and reducing conditions (NAS 

1976b), as found in organic-rich sediments. 

Aquatic organisms can convert selenium to both inert and soluble forms. Duckweed, phytoplankton, 

bacteria, and fungi have been demonstrated to synthesize selenoamino acids from absorbed inorganic 

selenium compounds (Maier et al. 1988). These selenoamino acids are not likely to be found at 

significant dissolved concentrations in water, however, because amino acids are rapidly catabolized by 
SELENIUM 248 

6. POTENTIAL FOR HUMAN EXPOSURE 

bacteria. Benthic bacteria and fungi are capable of methylating elemental and inorganic selenium salts 

(Chau et al. 1976). Hydrogen selenide can be formed in a reducing environment (Cutter 1982; NAS 

1976a). Both hydrogen selenide and the methylated forms of selenium are unstable in water and would 

be expected to rapidly volatilize to the atmosphere (Fishbein 1983). 

6.3.2.3 Sediment and Soil 

In soils, elemental selenium and inorganic selenium compounds such as sodium selenite can be 

methylated by microorganisms and subsequently volatilized to the atmosphere (Doran 1982; Fishbein 

1983; Shamberger 1981). Microorganisms such as Aeromonas, Flavobacterium, and Pseudomonas are 

suspected of methylating inorganic and organic selenium compounds to dimethyl selenide and dimethyl 

diselenide (Doran and Alexander 1976; Fishbein 1983; Reamer and Zoller 1980). Microbes cultured 

from rhizosphere of bulrush (Scirpus robustus) plants were shown to biomethylate soluble selenate and 

selenite and substantially volatilize these compounds over a 15-day incubation period (Azaizeh et al. 

1997). Temperature plays a significant role in the microorganism-mediated volatilization of selenium 

compounds; temperature reductions from 20 to 10 EC and from 20 to 4 EC resulted in 25 and 90% 

decreases, respectively, in the dimethyl selenide produced (Chau et al. 1976). Reamer and Zoller (1980) 

examined microbial transformation of selenium in aerobic sewage contaminated with elemental selenium 

and selenite. They found dimethyl selenide to be the principal microbial product at low selenite 

concentrations (1–10 mg/kg), whereas dimethyl diselenide and dimethyl selenone were the principal 

products at higher selenite concentrations (100–1,000 mg/kg). Dimethyl selenide was the only product 

recovered from sludge contaminated with elemental selenium (Reamer and Zoller 1980). In general, 

microorganisms appear to methylate organic selenium compounds more readily than either selenite or 

selenate (Maier et al. 1988). Elemental selenium is converted to methylated selenium compounds the 

least rapidly (Maier et al. 1988). Selenium methylation and subsequent return from the atmosphere as 

selenite in rainwater is likely to be the major natural process by which selenium cycling occurs in the 

environment (Doran 1982). 

Demethylation of the trimethylselenonium ion can also occur in soil. Microorganisms are evidently 

required for this reaction since it did not occur in autoclaved soil (Yamada et al. 1994). Selenium added 

to the soil as trimethylselenonium was not recovered in the soil, suggesting that trimethylselenonium was 

demethylated to gaseous selenium compounds, for example, dimethylselenide. 
SELENIUM 249 

6. POTENTIAL FOR HUMAN EXPOSURE 

Terrestrial plants take up soluble selenate and selenite and biosynthesize organic selenium compounds, 

predominantly selenomethionine and, to a lesser extent, selenocysteine. Selenates tend to be taken up by 

plants from soils more readily than selenites, in part because selenites tend to adsorb more strongly to 

soils (Dimes et al. 1988; Zhang et al. 1988). These compounds can be released to the soils once the plants 

die and decay. Water-soluble organic selenium compounds are also probably readily taken up by plants 

(Shamberger 1981; Shrift 1964). 

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT 

Selenium can be detected in most biological and nonbiological materials in the environment. Selenium 

occurs in aquatic and terrestrial organisms as well as in water, air, and soil. Among foods consumed by 

humans, meat products generally contain the highest concentration of selenium while vegetables and 

fruits contain the lowest. Brazil nuts contain extremely high levels of selenium since they grow in the 

foothills of the Andes Mountains, where the soils are high in selenium (Secor and Lisk 1989). Cereals 

contain intermediate levels of selenium. 

6.4.1 Air 

Background ambient air concentrations of selenium are generally in the ng/m3

 range (Harrison et al. 1971; 

John et al. 1973; Peirson et al. 1973). Dams et al. (1970) found concentrations of selenium in suspended 

air particulate matter of 2.5 ng/m3

 in Niles, Michigan, and 3.8 ng/m3 in East Chicago, Indiana. During 

1968–1969, 18 air samples collected around Buffalo, New York, showed a range of 3.7–9.7 ng/m3

 (Pillay 

et al. 1971). Based on these results, the National Academy of Sciences (NAS 1976a) has estimated that 

the average selenium concentration in the air is well below 10 ng/m3

. A monitoring study to determine 

the seasonal variation of pollutants in the air of Alaska was conducted from 1984 to 1987 (Sturges and 

Shaw 1993). The average concentrations of selenium in Poker Flats, Alaska were 0.035 ng/m3 (June 1 

through January 31, 1984–1987) and 0.067 ng/m3

 (February 1 through May 31, 1984–1987). The nearly 

2-fold increase in concentration during the spring months were attributed to local marine biogenic 

volatilization of selenium, and not a coal burning origin (Sturges and Shaw 1993). Selenium was 

detected in the ambient atmosphere at seven sites in the United Kingdom at concentrations ranging from 

0.1 to 42.3 ng/m3

 (Lee et al. 1994). The lowest levels were observed in the rural areas of Chilton and 

Windermere with mean concentrations of 1.3 and 0.9 ng/m3

, respectively. The highest mean 

concentration of 16.7 ng/m3

 was observed in the industrial area of Walsall. 
SELENIUM 250 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.4.2 Water 

Selenium has been detected in surface waters and groundwaters in the United States at generally low 

concentrations. Selenium has been detected in oceans at an average value of 9x10-5 mg/L (0.09 μg 

selenium/L) (Schutz and Turekiam 1965). In a study of selenium concentrations in major watersheds of 

the United States, selenium was detected in only 2 of 535 samples (<0.5%) at a concentration greater than 

the lowest detection limit of 0.010 mg/L (Lakin and Davidson 1967). Examination of the EPA STORET 

database for the state of North Carolina revealed that only 3.3% of 657 samples of surface water 

contained more than 0.001 mg/L, and the highest value was 0.012 mg/L (NCDNR 1986). Watersheds 

that receive selenium-contaminated waste water have high levels of selenium in surface water samples. 

The selenium concentration in Lake Belews, North Carolina has dropped from a maximum value of about 

0.020 mg/L (pre -1986) to <0.001 mg/L in 1996, due to the discontinued release of selenium laden waste 

water from a local coal fired power plant (Lemly 1997). The selenium concentration in portions of 

Pigeon River and Pigeon Lake, Michigan which receive waste water input from a coal fly ash disposal 

facility, were <0.001–0.0075 mg/L (Besser et al. 1996). 

High selenium levels are more likely to be found in irrigation return waters, seeps, springs, and shallow 

wells where seleniferous soils may contribute to the selenium content of the water. Glover et al. (1979) 

found that under unusual geological conditions, selenium concentrations in groundwater may reach 

0.60 mg/L. In another study conducted in a seleniferous area of South Dakota, 34 of 44 wells did not 

show any measurable selenium; however, the remaining 10 had concentrations ranging from 0.050 to 

0.339 mg/L (Smith and Westfall 1937). Selenium concentrations determined in 107 irrigation and 

44 livestock well waters in the San Joaquin area of California exceeded 0.010 mg/L in 26 wells, but 

exceeded 0.020 mg/L in only 11 wells (Oster et al. 1988a). The maximum concentration was 0.272 mg/L 

(Oster et al. 1988a). 

Selenium accumulation in agricultural drainage waters and basins has been documented in the western 

United States, particularly in California. The problem was first discovered in the Kesterson Wildlife 

Refuge in the San Joaquin Valley of California. In 1975, the U.S. Bureau of Reclamation finished 

construction of an 85-mile subsurface agricultural water drain that terminated in a series of evaporation 

ponds called Kesterson Reservoir. By 1983, however, it was confirmed that the drain waters contained 

high concentrations of selenium (>1.35 mg/L in some areas) leached from the soil by application of 
SELENIUM 251 

6. POTENTIAL FOR HUMAN EXPOSURE 

irrigation water (Maier et al. 1988). Because the high selenium levels produced death and deformities in 

fish and waterfowl, delivery of subsurface water to Kesterson was terminated in 1986 (Lewis 1988). 

Measurements of trace elements in the 27 other evaporation basins in the San Joaquin Valley have 

revealed only 3 basins with total selenium exceeding 0.10 mg/L and only 50 acres of evaporation basin 

cells with selenium concentrations in excess of 1.0 mg/L (CRWQCB 1988). 

6.4.3 Sediment and Soil 

Selenium is estimated to be the 69th most abundant element in the earth's crust, with an average 

concentration of 0.05–0.09 mg/kg (Glover et al. 1979). Chemically, selenium closely resembles sulfur. 

Consequently, sulfides of bismuth, iron, mercury, silver, copper, lead, and zinc have been found to 

contain selenium (Shamberger 1981). Selenium is concentrated in the sulfide minerals galena, 

chalcopyrite, arsenopyrite, sphalerite, pyrite, marcasite, and pyrrhotite (Coleman and Delevaux 1957). 

Jarosite and barite have also been found to contain selenium at low levels. The sulfides containing the 

highest selenium concentrations are those associated with uranium ores in sandstone-type deposits in the 

western United States. In the immediate vicinity of sandstone-type uranium deposits, selenium 

concentrations as high as 1,000 mg/kg have been found (Shamberger 1981). Hydrothermal ore is also 

known to contain high concentrations of selenium. The best known are epithermal gold, silver, antimony, 

and mercury deposits (Shamberger 1981). Selenium has been found in volcanic rocks in the western 

United States at concentrations as high as 120 mg/kg (Glover et al. 1979). 

Various studies estimated selenium concentration of most soils to be between 0.01 and 0.2 mg/kg 

(Sindeeva 1964). One study analyzed several thousand soil samples in the United States and found that 

most seleniferous soils contained <2 mg/kg, with a maximum concentration of <100 mg/kg (Rosenfeld 

and Beath 1964). The highest U.S. soil levels of selenium are found in areas of the West and Midwest. 

Atmospheric deposition of selenium from mining and smelting activities also appears to be a source to 

soils and plants (Glooschenko and Arafa 1988). In this study, an indirect relationship between distance 

from smelters and selenium concentration was shown using Sphagnum fuscum as an indicator. Washout 

of atmospheric selenium by precipitation appeared to be the primary mechanism for accumulating 

selenium in soils and plants in the vicinity of smelters (Glooschenko and Arafa 1988). 
SELENIUM 252 

6. POTENTIAL FOR HUMAN EXPOSURE 

Sandstone has been found to contain selenium in varying concentrations, but most probably contains 

<1 mg/kg (Rosenfeld and Beath 1964). However, sandstone in Wyoming has been found to contain 

>100 mg/kg (Beath et al. 1946). Generally, the selenium concentration of limestone is low; however, 

shales of the Niobrara formation in South Dakota have been found to contain over 40 mg/kg. The range 

of selenium concentrations in phosphate rocks is <1–300 mg/kg (NAS 1976a). Shales appear to contain 

consistently higher concentrations of selenium than limestone or sandstone. Despite the fact that shales 

vary so widely in their selenium concentration, they are fairly reliable indicators of soils high in selenium 

(NAS 1976a). 

The disposal of selenium contaminated waste water has resulted in elevated selenium levels in sediments 

of Lake Belews, North Carolina. The concentration of selenium in sediments ranged from 4 to 12 μg/g 

(pre-1986), but has dropped to 1–4 μg/g (1996) due to the discontinued release of selenium laden waste 

water from a local coal fired power plant (Lemly 1997). Selenium was measured in 445 surface soil 

samples from Florida with a concentration range of 0.01–4.62 μg/g and an arithmetic mean of 0.25 μg/g 

(Chen et al. 1999). Selenium was detected in soils and bed sediment from the South Platter River Basin 

at concentrations of 0.30–3.80 μg/g (Heiny and Tate 1997). The highest levels were observed in areas 

consisting of a high degree of Precambrian rock formation. 

6.4.4 Other Environmental Media 

Coal and Oil. Petroleum has been found to contain 500–950 mg/kg crude petroleum and 500– 

1,650 mg/kg heavy petroleum (Hashimoto et al. 1970). An average of 2.8 mg/kg coal has been reported 

for 138 samples from U.S. deposits (Pillay et al. 1969). 

Plants. Several species of grasses and herbaceous plants accumulate selenium, and some of these are 

endemic to the western United States. Primary accumulators are Astragalus, Oonopsis, Stanelya, 

Xylorhiza, and Machaeranthera. Secondary accumulators are Astor, Gatierreaia, Atriplex, Grindelia, 

Castillaja, and Comandra. Primary accumulators can contain 100–100,000 mg/kg of plant tissue, 

whereas secondary accumulators contain 25–100 mg/kg of plant tissue (dry weight). Nonaccumulator 

plants generally contain less than 25 mg of selenium/kg of plant tissue (dry weight) (Rosenfeld and Beath 

1964). In some plants, including the leaves of beets and cabbage, and in garlic, as much as 40–50% of the 

selenium may be in the form of selenate (Cappon 1981). 
SELENIUM 253 

6. POTENTIAL FOR HUMAN EXPOSURE 

A study by Arthur et al. (1992) showed an increased uptake of selenium by terrestrial plants growing on 

soil-capped fly ash landfill sites. Selenium concentrations rarely exceeded 5 mg/kg, and there were no 

signs of selenium toxicity to plants. A similar study by Shane et al. (1988) on greenhouse vegetables 

established that the uptake of selenium by these vegetables is proportional to the percentage of selenium 

in the growth medium. Another greenhouse study showed that four floating aquatic plants, Azolla 

caroliniana, Eichjornia crassipes, Salvinia rotundifolia, and Lemna minor, absorbed selenium quickly 

upon exposure (Horne 1991). 

Animals. Aquatic animals accumulate selenium from lakes and rivers high in selenium content. Fish in 

the Kesterson National Wildlife Refuge in California had selenium concentrations up to 96 mg/kg, and 

aquatic birds had levels up to 130 mg/kg (Barceloux 1999). Selenium was detected in fish from three 

sites of the Pigeon River and Pigeon Lake in Michigan (Besser et al. 1996). It was determined that 

selenium concentrations in fish at sites receiving seepage and effluents from a coal fly ash disposal 

facility were considerably higher than for fish upstream from the facility. Mean concentrations of 

selenium in white sucker and northern pike ranged from 0.46 to 0.88 μg/g in an uncontaminated portion 

of the river, while concentrations in a contaminated portion of the river and lake were 1.1–2.4 μg/g 

(Besser et al. 1996). The mean concentrations of selenium in the feathers of five species of birds at Clear 

Lake, California were 3.20 μg/g (osprey), 1.38 μg/g (western grebe), 2.51 μg/g (great blue heron), 

0.94 μg/g (turkey vulture), and 1.05 μg/g (mallard) (Cahill et al. 1998). Ospreys (which consume large 

mature fish) had the highest selenium levels, while turkey vultures (which rarely interact with the 

contaminated aquatic system) and mallards (which are semi-domesticated) had the lowest levels. 

Selenium was observed in 24 of 24 black-crowned night herons from the Delaware Bay at concentrations 

of 2.84–5.95 μg/g (Rattner et al. 2000). The highest levels were observed in herons from Pea Patch 

Island, an island adjacent to a shipping channel for the petrochemical industry. Selenium was observed in 

the liver of 70 out of 70 redheads (Athya americana) in Louisiana and Texas at concentrations of 

1.56–5.86 μg/g (Michot et al. 1994). The selenium concentration in moose liver from 12 areas of Sweden 

ranged from 0.0027 to 3.054 μg/g (Galgan and Frank 1995). The highest levels were observed in areas 

with a high degree of selenium deposition from industrial sources. 

Food. In a review of the foods that contribute the highest proportion of the daily selenium intake of 

human populations in the United States, Schubert et al. (1987) estimated selenium concentrations in over 

100 food items on the basis of 65 articles published after 1960. Table 6-3 presents the selenium 

concentrations for some of the food items analyzed. The quality of the data was evaluated on the basis of 

sample size, analytic method, sample handling, sampling plan, and analytic quality control. Schubert et 
SELENIUM 254 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-3. Selenium Concentrations in Foods in the United Statesa 

(mg selenium/kg, wet weight) 

Number of 

Food item Average Minimum Maximum acceptable samples 

Fruits and vegetables

 Apples, raw 0.004 0.003 0.006 5 

 Carrots, raw 0.017 0.006 0.029 5 

 Oranges 0.015 0.013 0.018 3 

Potatoes 0.013 0.004 0.023 7 

Grains, nuts, and cereals 

 Bread, white 0.32 0.23 0.54 6 

 Bread, whole wheat 0.44 0.28 0.67 3 

 Corn flakes 0.063 0.026 0.12 4 

 Special K 0.063 0.35 0.94 4 

 Egg noodles, dry 0.66 0.43 1.35 7 

 Egg noodles, cooked 

 Nuts, Brazilb 

0.19 

14.7 

0.14 

0.20 

0.42 

253 

2 

72 

Dairy products

 Whole milk 0.016 0.011 0.025 4 

 Swiss cheese 0.083 0.062 0.10 2 

 Cottage cheese 0.060 0.052 0.068 2 

Meat 

 Chicken, cooked 0.21 0.17 0.26 2 

 Beef, cooked 0.26 0.15 0.52 3 

 Pork/ham, fresh/cured 0.33 0.19 0.51 6 

Salami 0.20 0.13 0.33 2 

Seafoodc

 Salmon, canned 0.75 0.31 1.49 3 

 Shrimp, canned/cooked 0.64 0.21 1.61 4 

Swordfish 2.84 2.54 3.44 4 

Organ meats 

Beef liver, cooked 0.56 0.43 0.71 2 

Beef kidney, raw 1.70 1.45 2.32 4 

a

Food is the normal source of selenium which is essential for human health. Concentrations from Schubert et al. 

(1987), except where noted. 

b

Secor and Lisk (1989) 

c

Bioavailability of selenium from some fish may be lower than from other foods.
 
SELENIUM 255 

6. POTENTIAL FOR HUMAN EXPOSURE 

al. (1987) chose not to present standard deviations or standard errors of the samples because of the 

different sampling biases present in the studies. 

In general, fruits and vegetables were found to contain <0.01 mg/kg, whereas root vegetables contained 

higher concentrations of selenium (Table 6-3). Beale et al. (1990) found milk and meat to have the same 

range of selenium concentrations as Schubert et al. (1987). In another study, no apparent correlation 

existed between the selenium concentration of canned versus fresh fruits and vegetables (Morris and 

Levander 1970). 

Grain products varied greatly in their selenium concentration. Wheat bread and flour were high in 

selenium, whereas white bread and white flour contained considerably less selenium. Very low levels of 

selenium were found in certain processed cereals, such as corn flakes, but not in others, such as oat cereal 

(Morris and Levander 1970; Schubert et al. 1987). 

Dairy products contained variable concentrations of selenium as well, but, in general, contained lower 

levels than meat products. Organ meats (e.g., liver and kidney) and seafoods contained higher levels of 

selenium than poultry or beef (Morris and Levander 1970; Schubert et al. 1987). The U.S. Fish and 

Wildlife Service collected 315 whole fish samples from 109 stations nationwide and analyzed them for 

selenium. Selenium concentrations were as follows (wet weight): geometric mean of 0.42 μg/g, 

maximum of 2.3 μg/g, and 85th percentile concentration of 0.73 μg/g (Schmitt and Brumbagh 1990). 

Consumption of the foods with higher selenium levels contributes to the daily intake of adequate amounts 

of selenium. 

Analysis of commercial baby foods indicated that processing may reduce selenium levels of the food 

(Morris and Levander 1970). 

A recent survey conducted by the U.S. Food and Drug Administration (FDA), which analyzed foods 

consumed in the United States during the period of 1991–1999, detected selenium in 3,654 out of 

6,679 food samples analyzed (FDA 2000). The results of this survey are summarized in Table 6-4. 
SELENIUM 256 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-4. U.S. Food and Drug Administration—Total Diet Study (TDS)—Market 

Baskets 91-3 through 99-1 

Selenium—summary of results 

TDS food 

description 

TDS food 

number 

Number 

of results 

Number 

of not 

detected 

Number 

of traces 

Mean 

(mg/kg) 

Standard 

deviation 

(mg/kg) 

Minimum 

(mg/kg) 

Maximum 

(mg/kg) 

Median 

(mg/kg) 

Overall: 6,671 3,025 1,206 0.07 0.12 0 1.8 0.017 

Whole milk, 

fluid 

1 25 5 18 0.019 0.012 0 0.044 0.02 

Lowfat (2% 

fat) milk, 

fluid 

2 25 6 14 0.022 0.015 0 0.056 0.025 

Chocolate 

milk, fluid 

3 25 5 15 0.021 0.014 0 0.054 0.023 

Skim milk, 

fluid 

4 25 5 14 0.024 0.016 0 0.058 0.025 

Plain yogurt, 

lowfat 

6 25 5 9 0.031 0.019 0 0.068 0.033 

Chocolate 

milk shake, 

fast-food 

7 25 5 17 0.023 0.014 0 0.051 0.026 

Evaporated 

milk, canned 

8 25 4 4 0.043 0.024 0 0.102 0.047 

American, 

processed 

cheese 

10 25 0 3 0.183 0.025 0.097 0.231 0.178 

Cottage 

cheese, 4% 

milkfat 

11 25 2 4 0.083 0.039 0 0.178 0.08 

Cheddar 

cheese 

12 25 0 4 0.198 0.045 0.1 0.318 0.194 

Ground 

beef, pancooked 

13 25 0 1 0.197 0.052 0.127 0.333 0.187 

Beef chuck 

roast, baked 

14 25 0 0 0.251 0.058 0.15 0.379 0.24 

Beef steak, 

loin, pancooked 

16 25 0 1 0.256 0.063 0.13 0.439 0.24 

Ham, baked 17 25 0 1 0.29 0.077 0.12 0.42 0.278 

Pork chop, 

pan-cooked 

18 25 0 0 0.46 0.16 0.245 0.808 0.448 

Pork 19 25 0 4 0.215 0.094 0.066 0.556 0.207 

sausage, 

pan-cooked 

Pork bacon, 

pan-cooked 

20 25 0 0 0.38 0.15 0.186 0.836 0.323 

Pork roast, 

baked 

21 25 0 1 0.34 0.11 0.13 0.692 0.333 
SELENIUM 257 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-4. U.S. Food and Drug Administration—Total Diet Study (TDS)—Market 

Baskets 91-3 through 99-1 

Selenium—summary of results 

Number Standard 

TDS food TDS food Number of not Number Mean deviation Minimum Maximum Median 

description number of results detected of traces (mg/kg) (mg/kg) (mg/kg) (mg/kg) (mg/kg) 

Lamb chop, 

pan-cooked 

22 25 0 2 0.25 0.13 0.095 0.74 0.22 

Chicken, 

fried (breast, 

leg, and 

thigh) 

homemade 

24 25 0 2 0.25 0.1 0.067 0.465 0.243 

Turkey 

breast, 

roasted 

26 25 0 0 0.34 0.14 0.095 0.583 0.329 

Liver, beef, 

fried 

27 25 0 0 0.65 0.25 0.089 1.22 0.67 

Frankfurters, 

beef, boiled 

28 25 2 3 0.098 0.037 0 0.155 0.102 

Bologna, 

sliced 

29 25 0 5 0.134 0.037 0.07 0.239 0.13 

Salami, 

sliced 

30 25 0 3 0.202 0.046 0.079 0.313 0.197 

Tuna, 

canned in oil 

32 26 0 0 0.69 0.13 0.498 1.013 0.655 

Fish sticks, 

frozen, 

heated 

34 26 0 1 0.168 0.035 0.076 0.257 0.171 

Eggs, 

scrambled 

35 26 0 1 0.217 0.073 0.076 0.405 0.206 

Eggs, fried 36 25 0 0 0.278 0.084 0.149 0.454 0.259 

Eggs, boiled 37 25 0 2 0.27 0.1 0.023 0.477 0.274 

Pinto beans, 

dry boiled 

38 25 2 6 0.076 0.043 0 0.13 0.064 

Pork and 

beans, 

canned 

39 25 5 10 0.034 0.023 0 0.076 0.038 

Lima beans, 

immature, 

frozen, 

boiled 

42 25 17 8 0.005 0.009 0 0.036 0 

Green peas, 

fresh/frozen, 

boiled 

46 25 18 5 0.007 0.013 0 0.044 0 

Peanut 47 25 2 8 0.086 0.068 0 0.271 0.073 

butter, 

smooth 

Peanuts, dry 

roasted 

48 25 5 5 0.075 0.068 0 0.272 0.063 
SELENIUM 258 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-4. U.S. Food and Drug Administration—Total Diet Study (TDS)—Market 

Baskets 91-3 through 99-1 

Selenium—summary of results 

TDS food 

description 

TDS food 

number 

Number 

of results 

Number 

of not 

detected 

Number 

of traces 

Mean 

(mg/kg) 

Standard 

deviation 

(mg/kg) 

Minimum 

(mg/kg) 

Maximum 

(mg/kg) 

Median 

(mg/kg) 

White rice, 

cooked 

50 25 3 4 0.057 0.035 0 0.17 0.055 

Oatmeal, 

quick (1–3 

minutes), 

cooked 

51 25 2 4 0.058 0.034 0 0.18 0.052 

Wheat 

cereal, 

farina, quick 

(1– 

3 minutes), 

cooked 

52 25 3 3 0.076 0.047 0 0.205 0.069 

Corngrits, 

regular, 

cooked 

53 25 6 13 0.025 0.025 0 0.095 0.019 

Corn, 

fresh/frozen, 

boiled 

54 25 17 6 0.007 0.012 0 0.034 0 

Cream style 

corn, 

canned 

56 25 18 7 0.005 0.008 0 0.029 0 

Popcorn, 

popped in oil 

57 26 5 7 0.083 0.071 0 0.267 0.073 

White bread 58 25 0 3 0.211 0.075 0.05 0.363 0.197 

White roll 59 25 0 0 0.265 0.076 0.144 0.41 0.266 

Cornbread, 

homemade 

60 25 1 3 0.124 0.04 0 0.194 0.123 

Biscuit, from 

refrigerated 

dough, 

baked 

61 24 0 3 0.127 0.038 0.073 0.22 0.119 

Whole 

wheat bread 

62 25 0 0 0.32 0.079 0.198 0.48 0.32 

Tortilla, flour 63 25 0 1 0.227 0.099 0.032 0.469 0.229 

Rye bread 64 25 0 0 0.26 0.061 0.155 0.4 0.246 

Blueberry 

muffin, 

commercial 

65 25 0 3 0.113 0.04 0.065 0.246 0.108 

Saltine 

crackers 

66 26 1 5 0.098 0.036 0 0.197 0.1 

Corn chips 67 25 5 8 0.04 0.032 0 0.099 0.034 

Pancake 

from mix 

68 25 0 5 0.136 0.074 0.05 0.39 0.129 
SELENIUM 259 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-4. U.S. Food and Drug Administration—Total Diet Study (TDS)—Market 

Baskets 91-3 through 99-1 

Selenium—summary of results 

TDS food 

description 

TDS food 

number 

Number 

of results 

Number 

of not 

detected 

Number 

of traces 

Mean 

(mg/kg) 

Standard 

deviation 

(mg/kg) 

Minimum 

(mg/kg) 

Maximum 

(mg/kg) 

Median 

(mg/kg) 

Egg 

noodles, 

boiled 

69 25 0 1 0.218 0.082 0.052 0.373 0.232 

Macaroni, 

boiled 

70 26 0 1 0.242 0.087 0.034 0.43 0.245 

Corn flakes 71 26 5 4 0.057 0.048 0 0.195 0.05 

Fruitflavored, 

sweetened 

cereal 

72 25 0 5 0.075 0.026 0.031 0.14 0.079 

Shredded 

wheat cereal 

73 26 7 5 0.046 0.04 0 0.13 0.044 

Raisin bran 

cereal 

74 26 5 9 0.049 0.059 0 0.297 0.035 

Crisped rice 

cereal 

75 25 1 10 0.085 0.071 0 0.216 0.044 

Granola 

cereal 

76 26 0 2 0.144 0.053 0.066 0.244 0.14 

Oat ring 

cereal 

77 26 1 0 0.23 0.078 0 0.335 0.235 

Apple, red, 

raw 

78 26 25 1 0 0.002 0 0.011 0 

Orange, raw 79 26 24 2 0.001 0.003 0 0.012 0 

Banana, raw 80 26 16 8 0.009 0.014 0 0.054 0 

Watermelon, 

raw 

81 26 25 1 0 0.002 0 0.012 0 

Peach, raw 83 26 25 1 0 0.002 0 0.012 0 

Applesauce, 

bottled 

84 26 26 0 0 0 0 0 0 

Pear, raw 85 26 26 0 0 0 0 0 0 

Strawberries 86 25 23 2 0.001 0.003 0 0.012 0 

, raw 

Fruit 

cocktail, 

canned in 

heavy syrup 

87 26 26 0 0 0 0 0 0 

Grapes, 

red/green, 

seedless, 

raw 

88 26 26 0 0 0 0 0 0 

Cantaloupe, 

raw 

89 26 16 10 0.007 0.009 0 0.025 0 

Plums, raw 91 26 25 1 0 0.002 0 0.012 0 
SELENIUM 260 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-4. U.S. Food and Drug Administration—Total Diet Study (TDS)—Market 

Baskets 91-3 through 99-1 

Selenium—summary of results 

TDS food 

description 

TDS food 

number 

Number 

of results 

Number 

of not 

detected 

Number 

of traces 

Mean 

(mg/kg) 

Standard 

deviation 

(mg/kg) 

Minimum 

(mg/kg) 

Maximum 

(mg/kg) 

Median 

(mg/kg) 

Grapefruit, 

raw 

92 26 24 2 0.001 0.003 0 0.011 0 

Pineapple, 

canned in 

juice 

93 26 25 1 0.001 0.003 0 0.017 0 

Sweet 

cherries, raw 

94 20 20 0 0 0 0 0 0 

Raisins, 

dried 

95 25 24 1 0.001 0.003 0 0.014 0 

Prunes, 

dried 

96 25 25 0 0 0 0 0 0 

Avocado, 

raw 

97 25 24 1 0.001 0.006 0 0.028 0 

Orange 

juice, from 

frozen 

98 25 24 2 0.001 0.003 0 0.015 0 

concentrate 

Apple juice, 

bottled 

99 25 24 1 0.002 0.008 0 0.04 0 

Grapefruit 

juice, from 

frozen 

100 26 26 0 0 0 0 0 0 

concentrate 

Prune juice, 

bottled 

103 26 25 1 0 0.002 0 0.011 0 

Lemonade, 

from frozen 

105 26 25 0 0.002 0.009 0 0.047 0 

concentrate 

Spinach, 

fresh/frozen, 

boiled 

107 25 18 7 0.003 0.005 0 0.015 0 

Collards, 

fresh/frozen 

108 25 17 7 0.005 0.009 0 0.041 0 

Iceberg 

lettuce, raw 

109 26 24 2 0.001 0.004 0 0.014 0 

Cabbage, 

fresh, boiled 

110 26 21 4 0.003 0.007 0 0.03 0 

Coleslaw 

with 

dressing, 

homemade 

111 26 17 8 0.011 0.016 0 0.047 0 

Sauerkraut, 

canned 

112 26 14 11 0.009 0.015 0 0.071 0 
SELENIUM 261 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-4. U.S. Food and Drug Administration—Total Diet Study (TDS)—Market 

Baskets 91-3 through 99-1 

Selenium—summary of results 

TDS food 

description 

TDS food 

number 

Number 

of results 

Number 

of not 

detected 

Number 

of traces 

Mean 

(mg/kg) 

Standard 

deviation 

(mg/kg) 

Minimum 

(mg/kg) 

Maximum 

(mg/kg) 

Median 

(mg/kg) 

Broccoli, 

fresh/frozen, 

boiled 

113 26 16 8 0.011 0.027 0 0.134 0 

Celery, raw 114 26 24 2 0.001 0.003 0 0.012 0 

Asparagus, 

fresh/frozen, 

boiled 

115 26 5 11 0.042 0.045 0 0.217 0.034 

Cauliflower, 

fresh/frozen, 

boiled 

116 26 17 7 0.009 0.022 0 0.103 0 

Tomato, red, 117 25 22 3 0.002 0.005 0 0.019 0 

raw 

Tomato 

sauce, plain, 

bottled 

119 26 23 3 0.003 0.008 0 0.037 0 

Green 

beans, 

fresh/frozen, 

boiled 

121 26 23 3 0.001 0.004 0 0.013 0 

Cucumber, 

raw 

123 26 25 1 0 0.002 0 0.011 0 

Summer 

squash, 

fresh/frozen, 

boiled 

124 26 22 4 0.002 0.005 0 0.019 0 

Green 125 26 26 0 0 0 0 0 0 

pepper, raw 

Winter 

squash, 

fresh/frozen, 

baked, 

mashed 

126 26 24 2 0.001 0.003 0 0.012 0 

Onion, 

mature, raw 

128 26 18 8 0.006 0.01 0 0.039 0 

Radish, raw 132 26 25 1 0 0.002 0 0.011 0 

French fries, 

frozen, 

heated 

134 26 25 1 0.001 0.003 0 0.016 0 

Mashed 135 26 21 5 0.004 0.009 0 0.035 0 

potatoes, 

from flakes 

White 136 26 25 1 0.001 0.005 0 0.028 0 

potato, 

boiled 

without skin 
SELENIUM 262 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-4. U.S. Food and Drug Administration—Total Diet Study (TDS)—Market 

Baskets 91-3 through 99-1 

Selenium—summary of results 

Number Standard 

TDS food TDS food Number of not Number Mean deviation Minimum Maximum Median 

description number of results detected of traces (mg/kg) (mg/kg) (mg/kg) (mg/kg) (mg/kg) 

White 137 26 20 6 0.004 0.007 0 0.02 0 

potato, 

baked with 

skin 

Potato chips 138 26 13 8 0.026 0.046 0 0.217 0.006 

Scalloped 

potatoes, 

homemade 

139 26 14 10 0.012 0.015 0 0.048 0 

Sweet 140 26 22 3 0.004 0.009 0 0.033 0 

potato, 

fresh, baked 

Spaghetti 

with tomato 

142 26 0 4 0.123 0.035 0.048 0.2 0.116 

sauce and 

meatballs, 

homemade 

Beef stew 143 26 1 5 0.07 0.026 0 0.12 0.071 

with 

potatoes, 

carrots, and 

onion, 

homemade 

Macaroni 146 26 0 2 0.195 0.055 0.076 0.339 0.189 

and cheese, 

from box mix 

Quarterpound 

hamburger 

on bun, fastfood 

147 26 0 2 0.177 0.046 0.091 0.3 0.173 

Meatloaf, 

homemade 

148 26 0 2 0.191 0.048 0.074 0.3 0.195 

Spaghetti 

with tomato 

149 26 0 6 0.106 0.028 0.06 0.187 0.1 

sauce, 

canned 

Lasagna 

with meat, 

homemade 

151 26 0 4 0.147 0.032 0.093 0.213 0.147 

Chicken 152 26 3 3 0.071 0.032 0 0.127 0.076 

potpie, 

frozen, 

heated 
SELENIUM 263 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-4. U.S. Food and Drug Administration—Total Diet Study (TDS)—Market 

Baskets 91-3 through 99-1 

Selenium—summary of results 

Number Standard 

TDS food TDS food Number of not Number Mean deviation Minimum Maximum Median 

description number of results detected of traces (mg/kg) (mg/kg) (mg/kg) (mg/kg) (mg/kg) 

Chicken 155 26 5 9 0.028 0.018 0 0.06 0.03 

noodle soup, 

canned, 

condensed, 

prepared 

with water 

Tomato 156 26 22 4 0.002 0.005 0 0.017 0 

soup, 

canned, 

condensed, 

prepared 

with water 

Vegetable 

beef soup, 

canned, 

condensed, 

prepared 

with water 

157 26 11 15 0.01 0.01 0 0.026 0.013 

White 160 26 6 6 0.032 0.022 0 0.076 0.035 

sauce, 

homemade 

Dill 161 26 24 2 0.001 0.004 0 0.017 0 

cucumber 

pickles 

Margarine, 

stick, regular 

(salted) 

162 25 24 1 0 0.002 0 0.012 0 

Butter, 

regular 

(salted) 

164 26 21 5 0.003 0.007 0 0.021 0 

Mayonnaise, 

regular, 

bottled 

166 26 11 12 0.021 0.021 0 0.078 0.024 

Half & half 167 26 6 18 0.019 0.013 0 0.042 0.021 

cream 

Cream 168 26 26 0 0 0 0 0 0 

substitute, 

frozen 

White sugar, 

granulated 

169 26 26 0 0 0 0 0 0 

Pancake 170 26 26 0 0 0 0 0 0 

syrup 

Honey 172 26 26 0 0 0 0 0 0 

Tomato 173 26 22 4 0.002 0.005 0 0.016 0 

catsup 
SELENIUM 264 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-4. U.S. Food and Drug Administration—Total Diet Study (TDS)—Market 

Baskets 91-3 through 99-1 

Selenium—summary of results 

Number Standard 

TDS food TDS food Number of not Number Mean deviation Minimum Maximum Median 

description number of results detected of traces (mg/kg) (mg/kg) (mg/kg) (mg/kg) (mg/kg) 

Chocolate 175 26 6 15 0.027 0.024 0 0.087 0.025 

pudding, 

from instant 

mix 

Vanilla 177 24 6 10 0.026 0.016 0 0.046 0.03 

flavored light 

ice cream 

Chocolate 178 26 6 11 0.035 0.022 0 0.077 0.041 

cake with 

chocolate 

icing, 

commercial 

Yellow cake 179 26 7 5 0.035 0.024 0 0.075 0.042 

with white 

icing, 

prepared 

from cake 

and icing 

mixes 

Sweet 182 26 0 5 0.128 0.04 0.043 0.22 0.123 

roll/Danish, 

commercial 

Chocolate 183 26 6 5 0.043 0.032 0 0.123 0.045 

chip 

cookies, 

commercial 

Sandwich 184 26 5 15 0.032 0.022 0 0.081 0.029 

cookies with 

creme filling, 

commercial 

Apple pie, 

fresh/frozen, 

commercial 

185 26 17 9 0.007 0.011 0 0.033 0 

Pumpkin 

pie, 

fresh/frozen, 

commercial 

186 26 6 11 0.033 0.021 0 0.076 0.037 

Milk 187 26 4 4 0.046 0.025 0 0.11 0.047 

chocolate 

candy bar, 

plain 

Caramel 188 26 10 15 0.017 0.015 0 0.05 0.022 

candy 

Gelatin 190 26 25 1 0.001 0.003 0 0.017 0 

dessert, any 

flavor 
SELENIUM 265 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-4. U.S. Food and Drug Administration—Total Diet Study (TDS)—Market 

Baskets 91-3 through 99-1 

Selenium—summary of results 

Number Standard 

TDS food TDS food Number of not Number Mean deviation Minimum Maximum Median 

description number of results detected of traces (mg/kg) (mg/kg) (mg/kg) (mg/kg) (mg/kg) 

Cola 191 26 25 1 0.001 0.003 0 0.014 0 

carbonated 

beverage 

Fruit drink, 193 26 25 0 0.001 0.006 0 0.032 0 

from powder 

Low-calorie 194 26 26 0 0 0 0 0 0 

cola 

carbonated 

beverage 

Coffee, 196 26 24 2 0.001 0.006 0 0.032 0 

decaffeinate 

d, from 

instant 

Tea, from 197 26 25 1 0.001 0.006 0 0.032 0 

tea bag 

Beer 198 26 21 5 0.002 0.005 0 0.015 0 

Dry table 199 26 24 2 0.002 0.008 0 0.04 0 

wine 

Whiskey 200 26 25 1 0 0.001 0 0.007 0 

Tap water 201 26 25 1 0 0 0 0.002 0 

Milk-based 202 25 6 18 0.017 0.011 0 0.03 0.021 

infant 

formula, 

high iron, 

ready-tofeed 

Milk-based 203 25 6 18 0.018 0.011 0 0.037 0.021 

infant 

formula, low 

iron, readyto- feed 

Beef, 205 26 6 12 0.028 0.02 0 0.075 0.026 

strained/ 

junior 

Chicken, 207 25 0 1 0.129 0.024 0.063 0.181 0.134 

strained/ 

junior, 

with/without 

broth or 

gravy 
SELENIUM 266 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-4. U.S. Food and Drug Administration—Total Diet Study (TDS)—Market 

Baskets 91-3 through 99-1 

Selenium—summary of results 

Number Standard 

TDS food TDS food Number of not Number Mean deviation Minimum Maximum Median 

description number of results detected of traces (mg/kg) (mg/kg) (mg/kg) (mg/kg) (mg/kg) 

Chicken/ 

turkey with 

vegetables, 

high/lean 

meat, 

strained/ 

junior 

208 2 0 2 0.064 0.004 0.061 0.066 0.064 

Beef with 209 2 2 0 0 0 0 0 0 

vegetables, 

high/lean 

meat, 

strained/ 

junior 

Ham with 210 2 0 2 0.102 0.033 0.079 0.125 0.102 

vegetables, 

high/lean 

meat, 

strained/ 

junior 

Vegetables 

and beef, 

strained/ 

junior 

211 25 14 11 0.007 0.009 0 0.033 0 

Vegetables 

and chicken, 

strained/ 

junior 

212 26 7 19 0.015 0.015 0 0.073 0.012 

Vegetables 

and ham, 

strained/ 

junior 

213 26 7 18 0.016 0.012 0 0.041 0.018 

Chicken 214 26 6 10 0.029 0.018 0 0.064 0.032 

noodle 

dinner, 

strained/ 

junior 

Macaroni, 215 26 5 10 0.028 0.017 0 0.06 0.032 

tomatoes, 

and beef, 

strained/ 

junior 

Turkey and 

rice, 

strained/ 

junior 

216 26 7 14 0.025 0.022 0 0.095 0.025 
SELENIUM 267 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-4. U.S. Food and Drug Administration—Total Diet Study (TDS)—Market 

Baskets 91-3 through 99-1 

Selenium—summary of results 

Number Standard 

TDS food TDS food Number of not Number Mean deviation Minimum Maximum Median 

description number of results detected of traces (mg/kg) (mg/kg) (mg/kg) (mg/kg) (mg/kg) 

Carrots, 218 26 25 1 0.001 0.005 0 0.026 0 

strained/ 

junior 

Green 219 26 24 2 0.001 0.005 0 0.019 0 

beans, 

strained/ 

junior 

Mixed 220 26 17 7 0.009 0.018 0 0.081 0 

vegetables, 

strained/ 

junior 

Sweet 221 26 26 0 0 0 0 0 0 

potatoes, 

strained/ 

junior 

Creamed 222 26 11 9 0.017 0.021 0 0.074 0.012 

corn, 

strained/ 

junior 

Peas, 223 26 23 3 0.001 0.004 0 0.016 0 

strained/ 

junior 

Creamed 224 25 6 13 0.022 0.017 0 0.068 0.026 

spinach, 

strained/ 

junior 

Applesauce, 225 26 24 2 0.001 0.003 0 0.012 0 

strained/ 

junior 

Peaches, 226 26 26 0 0 0 0 0 0 

strained/ 

junior 

Pears, 227 25 24 1 0 0.002 0 0.012 0 

strained/ 

junior 

Apple juice, 230 25 25 0 0 0 0 0 0 

strained 

Orange 231 26 26 0 0 0 0 0 0 

juice, 

strained 

Custard 232 26 5 10 0.032 0.019 0 0.071 0.035 

pudding, 

strained/ 

junior 
SELENIUM 268 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-4. U.S. Food and Drug Administration—Total Diet Study (TDS)—Market 

Baskets 91-3 through 99-1 

Selenium—summary of results 

Number Standard 

TDS food TDS food Number of not Number Mean deviation Minimum Maximum Median 

description number of results detected of traces (mg/kg) (mg/kg) (mg/kg) (mg/kg) (mg/kg) 

Fruit 233 26 25 1 0 0.002 0 0.011 0 

dessert/ 

pudding, 

strained/ 

junior 

Fruit­ 235 26 7 14 0.022 0.015 0 0.047 0.024 

flavored 

yogurt, 

lowfat (fruit 

mixed in) 

Swiss 236 26 0 5 0.18 0.054 0.109 0.368 0.174 

cheese 

Cream 237 26 4 8 0.053 0.031 0 0.099 0.054 

cheese 

Veal cutlet, 

pan-cooked 

238 26 0 1 0.165 0.045 0.098 0.354 0.162 

Ham 239 26 0 0 0.237 0.078 0.096 0.374 0.22 

luncheon 

meat, sliced 

Chicken 240 25 0 1 0.27 0.12 0.09 0.623 0.228 

breast, 

roasted 

Chicken 241 25 0 1 0.2 0.1 0.052 0.595 0.177 

nuggets, 

fast-food 

Chicken, 

fried (breast, 

leg, and 

thigh), fastfood 

242 25 0 1 0.218 0.065 0.131 0.353 0.21 

Haddock, 

pan-cooked 

243 19 0 0 0.397 0.076 0.256 0.503 0.4 

Shrimp, 

boiled 

244 25 0 0 0.38 0.1 0.2 0.574 0.369 

Kidney 

beans, dry, 

boiled 

245 26 8 12 0.02 0.017 0 0.051 0.019 

Peas, 

mature, dry, 

boiled 

246 26 10 4 0.05 0.09 0 0.457 0.034 

Mixed nuts, 

no peanuts, 

dry roasted 

247 25 1 0 0.53 0.39 0 1.8 0.44 

Cracked 248 26 0 0 0.285 0.065 0.209 0.448 0.269 

wheat bread 
SELENIUM 269 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-4. U.S. Food and Drug Administration—Total Diet Study (TDS)—Market 

Baskets 91-3 through 99-1 

Selenium—summary of results 

TDS food 

description 

TDS food 

number 

Number 

of results 

Number 

of not 

detected 

Number 

of traces 

Mean 

(mg/kg) 

Standard 

deviation 

(mg/kg) 

Minimum 

(mg/kg) 

Maximum 

(mg/kg) 

Median 

(mg/kg) 

Bagel, plain 249 26 0 0 0.311 0.085 0.165 0.518 0.299 

English 

muffin, plain, 

toasted 

250 26 0 0 0.263 0.068 0.144 0.402 0.25 

Graham 

crackers 

251 26 4 3 0.055 0.03 0 0.1 0.057 

Butter-type 

crackers 

252 26 4 2 0.061 0.031 0 0.102 0.069 

Apricot, raw 253 21 19 2 0.001 0.004 0 0.015 0 

Peach, 

canned in 

light/medium 

syrup 

254 26 26 0 0 0 0 0 0 

Pear, 

canned in 

light syrup 

255 26 26 0 0 0 0 0 0 

Pineapple 

juice, from 

frozen 

256 26 26 0 0 0 0 0 0 

concentrate 

Grape juice, 

from frozen 

257 26 26 0 0 0 0 0 0 

concentrate 

French fries, 

fast-food 

258 26 22 4 0.003 0.007 0 0.023 0 

Carrot, 

fresh, boiled 

259 26 22 4 0.002 0.006 0 0.027 0 

Tomato, 

stewed, 

canned 

260 26 24 2 0.001 0.003 0 0.014 0 

Tomato 

juice, bottled 

261 26 20 6 0.004 0.007 0 0.023 0 

Beets, 

fresh/frozen, 

boiled 

262 25 22 3 0.002 0.006 0 0.023 0 

Brussels 263 26 16 8 0.009 0.013 0 0.044 0 

sprouts, 

fresh/frozen, 

boiled 

Mushrooms, 

raw 

264 26 2 3 0.108 0.054 0 0.227 0.095 

Eggplant, 

fresh, boiled 

265 26 26 0 0 0 0 0 0 
SELENIUM 270 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-4. U.S. Food and Drug Administration—Total Diet Study (TDS)—Market 

Baskets 91-3 through 99-1 

Selenium—summary of results 

Number Standard 

TDS food TDS food Number of not Number Mean deviation Minimum Maximum Median 

description number of results detected of traces (mg/kg) (mg/kg) (mg/kg) (mg/kg) (mg/kg) 

Turnip, 

fresh/frozen, 

boiled 

266 26 23 3 0.002 0.006 0 0.025 0 

Okra, 

fresh/frozen, 

boiled 

267 26 22 3 0.003 0.008 0 0.03 0 

Mixed 268 26 20 6 0.004 0.008 0 0.032 0 

vegetables, 

frozen, 

boiled 

Beef 269 26 0 0 0.191 0.043 0.121 0.311 0.183 

stroganoff, 

homemade 

Green 270 26 3 4 0.065 0.029 0 0.113 0.066 

peppers 

stuffed with 

beef and 

rice, 

homemade 

Chili con 271 26 3 6 0.052 0.025 0 0.09 0.057 

carne with 

beans, 

homemade 

Tuna noodle 272 26 0 1 0.173 0.042 0.107 0.281 0.166 

casserole, 

homemade 

Salisbury 

steak with 

273 26 6 4 0.034 0.022 0 0.062 0.041 

gravy, 

potatoes, 

and 

vegetable, 

frozen meal, 

heated 

Turkey with 

gravy, 

dressing, 

potatoes, 

and 

274 26 0 5 0.093 0.025 0.051 0.17 0.091 

vegetable, 

frozen meal, 

heated 
SELENIUM 271 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-4. U.S. Food and Drug Administration—Total Diet Study (TDS)—Market 

Baskets 91-3 through 99-1 

Selenium—summary of results 

Number Standard 

TDS food TDS food Number of not Number Mean deviation Minimum Maximum Median 

description number of results detected of traces (mg/kg) (mg/kg) (mg/kg) (mg/kg) (mg/kg) 

Quarter­ 275 26 0 0 0.18 0.041 0.108 0.331 0.18 

pound 

cheeseburger on 

bun, fastfood 

Fish 276 26 0 0 0.184 0.04 0.109 0.281 0.189 

sandwich on 

bun, fastfood 

Frankfurter 277 26 0 3 0.199 0.048 0.096 0.315 0.197 

on bun, fastfood 

Egg, 278 26 0 0 0.263 0.079 0.095 0.451 0.256 

cheese, and 

ham on 

English 

muffin, fastfood 

Taco/ 279 26 2 3 0.103 0.039 0 0.161 0.104 

tostada, 

from 

Mexican 

carry-out 

Cheese 280 26 0 0 0.239 0.053 0.138 0.332 0.235 

pizza, 

regular 

crust, from 

pizza carryout 

Cheese and 281 26 0 0 0.229 0.067 0.068 0.381 0.225 

pepperoni 

pizza, 

regular 

crust, from 

pizza carryout 

Beef chow 282 26 3 5 0.068 0.043 0 0.192 0.071 

mein, from 

Chinese 

carry-out 

Bean with 283 26 7 19 0.015 0.013 0 0.052 0.014 

bacon/pork 

soup, 

canned, 

condensed, 

prepared 

with water 
SELENIUM 272 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-4. U.S. Food and Drug Administration—Total Diet Study (TDS)—Market 

Baskets 91-3 through 99-1 

Selenium—summary of results 

Number Standard 

TDS food TDS food Number of not Number Mean deviation Minimum Maximum Median 

description number of results detected of traces (mg/kg) (mg/kg) (mg/kg) (mg/kg) (mg/kg) 

Mushroom 284 26 5 18 0.021 0.017 0 0.061 0.019 

soup, 

canned, 

condensed, 

prepared 

with whole 

milk 

Clam 285 26 4 12 0.032 0.018 0 0.06 0.036 

chowder, 

New 

England, 

canned, 

condensed, 

prepared 

with whole 

milk 

Vanilla ice 286 26 6 19 0.019 0.012 0 0.043 0.021 

cream 

Fruit flavor 287 26 21 4 0.005 0.013 0 0.059 0 

sherbet 

Popsicle, 

any flavor 

288 26 25 1 0.001 0.006 0 0.03 0 

Chocolate 289 26 9 15 0.02 0.017 0 0.056 0.025 

snack cake 

with 

chocolate 

icing 

Cake 290 26 0 7 0.097 0.036 0.032 0.164 0.097 

doughnuts 

with icing, 

any flavor, 

from 

doughnut 

store 

Brownies, 

commercial 

291 26 4 7 0.045 0.026 0 0.096 0.049 

Sugar 

cookies, 

commercial 

292 26 4 13 0.039 0.025 0 0.091 0.035 

Suckers, 

any flavor 

293 26 24 1 0.003 0.014 0 0.07 0 

Pretzels, 

hard, salted, 

any shape 

294 26 5 7 0.04 0.025 0 0.094 0.043 
SELENIUM 273 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-4. U.S. Food and Drug Administration—Total Diet Study (TDS)—Market 

Baskets 91-3 through 99-1 

Selenium—summary of results 

TDS food 

description 

TDS food 

number 

Number 

of results 

Number 

of not 

detected 

Number 

of traces 

Mean 

(mg/kg) 

Standard 

deviation 

(mg/kg) 

Minimum 

(mg/kg) 

Maximum 

(mg/kg) 

Median 

(mg/kg) 

Chocolate 295 26 20 5 0.006 0.013 0 0.054 0 

syrup 

dessert 

topping 

Jelly, any 

flavor 

296 26 25 1 0.001 0.005 0 0.025 0 

Sweet 

cucumber 

pickles 

297 26 22 4 0.002 0.005 0 0.017 0 

Yellow 

mustard 

298 26 0 0 0.33 0.13 0.103 0.724 0.308 

Black olives 299 26 25 0 0.001 0.007 0 0.038 0 

Sour cream 300 26 4 20 0.027 0.022 0 0.1 0.022 

Brown 301 26 7 9 0.031 0.025 0 0.094 0.032 

gravy, 

homemade 

French 

salad 

dressing, 

regular 

302 26 14 10 0.017 0.036 0 0.184 0 

Italian salad 

dressing, 

low-calorie 

303 26 24 2 0.002 0.006 0 0.023 0 

Olive/ 

safflower oil 

304 26 25 1 0.001 0.003 0 0.014 0 

Coffee, from 

ground 

305 26 26 0 0 0 0 0 0 

Fruitflavored 

carbonated 

beverage 

306 26 25 1 0.001 0.004 0 0.022 0 

Fruit drink, 

canned 

307 26 24 2 0.001 0.005 0 0.022 0 

Martini 308 26 26 0 0 0 0 0 0 

Soy-based 

infant 

formula, 

ready-tofeed 

309 26 8 17 0.013 0.009 0 0.023 0.016 

Egg yolk, 

strained/ 

junior 

310 12 0 0 0.293 0.026 0.253 0.33 0.292 
SELENIUM 274 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-4. U.S. Food and Drug Administration—Total Diet Study (TDS)—Market 

Baskets 91-3 through 99-1 

Selenium—summary of results 

Number Standard 

TDS food TDS food Number of not Number Mean deviation Minimum Maximum Median 

description number of results detected of traces (mg/kg) (mg/kg) (mg/kg) (mg/kg) (mg/kg) 

Rice infant 311 26 5 3 0.051 0.03 0 0.093 0.06 

cereal, 

instant, 

prepared 

with whole 

milk 

Bananas 312 20 9 11 0.011 0.011 0 0.032 0.016 

with tapioca, 

strained/ 

junior 

Beets, 313 26 25 1 0 0.002 0 0.01 0 

strained/ 

junior 

Split peas 314 15 15 0 0 0 0 0 0 

with 

vegetables 

and 

ham/bacon, 

strained/ 

junior 

Teething 316 26 8 18 0.015 0.011 0 0.038 0.017 

biscuits 

Rice cereal 317 26 0 0 0.192 0.052 0.109 0.356 0.188 

with apple, 

strained/ 

junior 

Squash, 318 6 0 0 0.285 0.052 0.205 0.341 0.29 

strained/ 

junior 
SELENIUM 275 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE 

Because selenium is ubiquitous in the environment and has been detected in so many media, exposure of 

the general population to selenium can occur in a variety of ways, including occupational exposure, 

inhalation, and ingestion of selenium via drinking water, foods, and selenium supplements. For exposure 

via the food pathway, Schubert et al. (1987) estimated that beef, white bread, pork or ham, chicken, and 

eggs provide over 50% of the daily selenium intake in the U.S. population. FDA (1982a) estimated that 

the greatest portion of daily selenium intake occurs from the ingestion of grains and cereals (51.8%). 

Meat, fish, and poultry were estimated to contribute 36.4% and dairy products were estimated to 

contribute 9.7% (FDA 1982a). 

Various estimates of the selenium intake for Americans have ranged from 0.071 to 0.152 mg/day (DHHS 

2002; FDA 1982a; Levander 1987; Pennington et al. 1989; Schrauzer and White 1978; Schubert et al. 

1987; Welsh et al. 1981). Schubert et al. (1987) estimated the intake of selenium for the U.S. population 

to be 0.071 mg/day. They based their estimate on their review of selenium concentrations in different 

types of foods and the amount of each type of food eaten. The amount of each food type eaten daily was 

estimated from the U.S. Department of Agriculture's 1977–1978 Nationwide Food Consumption Survey 

(NFCS). Welsh et al. (1981) estimated the mean daily selenium intake of a group of 22 Maryland 

residents to be 0.081 mg/day (the median was 0.074 mg/day). In California, the mean daily selenium 

intake of eight individuals was estimated to be 0.127 mg/day (Schrauzer and White 1978). FDA (1982a) 

estimated the average daily selenium intake of the U.S. population to be 0.1523 mg/day (152.3 μg/day). 

Pennington et al. (1989) estimated the daily dietary intake of selenium by age group and by sex between 

1982 and 1986, based on FDA's Total Diet Studies for those years, to be between 0.020 mg/day 

(20 μg/day) for infants and 0.120 mg/day (120 μg/day) for adult males between 25 and 30 years of age. 

Based on information collected from 1988-94 in the third National Health and Nutrition Examination 

Survey (NHANES III), the dietary intake of selenium was estimated by sex and age in the United States 

(see Table 6-5). Based on data from this study, the average dietary intake for all ages and both sexes was 

estimated to be 0.114 mg/day (DHHS 2002). These values are sufficient to meet the RDA for selenium of 

0.055 mg/day for men and women (NAS 2000). 

Both inorganic selenium and selenomethionine are found in selenium supplements. The amounts in these 

supplements generally range from 10 to 25 μg/tablet (Goodman et al. 1990), although current products are 
SELENIUM 276 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-5. Selenium Dietary Intake (μg/day) by Sex and Age for the Total U.S. 

Population, 1988–1994 (DHHS 2002)a
 

Sex and age Sample size Mean SEM Median 

Both sexes 

All agesb

 29,105 114 1.1 99 

Under 6 yearsb

 6,871 66 0.8 62 

6–11 years 3,134 96 1.7 87 

12–19 years 3,121 117 2.4 102 

20–59 years 10,940 127 1.6 111 

60 years and over 5,039 100 1.3 89 

Male 

All agesb

 13,923 134 1.6 118 

Under 6 yearsb

 3,410 69 1.0 64 

6–11 years 1,581 102 2.8 92 

12–19 years 1,462 140 3.1 125 

20–59 years 5,019 153 2.1 137 

60 years and over 2,451 118 1.7 106 

Female 

All agesb

 15,182 94 1.1 85 

Under 6 yearsb

 3,461 63 0.9 59 

6–11 years 1,553 90 1.6 82 

12–19 years 1,659 93 2.4 87 

20–59 years 5,921 102 1.8 92 

60 years and over 2,588 87 1.6 78 

a

Based on information collected in the third National Health and Nutrition Examination Survey (NHANES III). b

Excludes nursing infants and children, includes data for poverty income ratio. 

SEM = Standard error of the mean 
SELENIUM 277 

6. POTENTIAL FOR HUMAN EXPOSURE 

available in the 100–200 μg/tablet level. A guide to vitamin and minerals recommends that not more than 

200 μg selenium/day should be taken in any form (Hendler 1990). 

The mean whole blood selenium concentration of residents from 19 U.S. cities ranged from 0.10 to 

0.34 mg/L with a mean value of 0.21 mg/L (Barceloux 1999). A synopsis of selenium concentrations in 

human tissues has been summarized in Table 3-6. Based on information collected from 1988 to 94 in 

NHANES III, the serum concentration of selenium was estimated by sex and age in the United States (see 

Table 6-6). Based on data from this study, the mean selenium serum concentration for all ages and both 

sexes was estimated to be 0.125 mg/L (DHHS 1997). 

The National Occupation Hazard Survey (NOHS), conducted by the National Institute for Occupational 

Safety and Health (NIOSH), estimated that 108,682 workers in 15,127 plants were potentially exposed to 

selenium in the workplace in 1970 (NOHS 1976). These estimates were derived from observations of the 

actual use of selenium (1% of total estimate), the use of trade name products known to contain selenium 

(4%), and the use of generic products suspected of containing the selenium compounds (95%). The 

largest numbers of exposed workers were heavy equipment mechanics, painters, mechanics in service 

stations, and special trade contractors. Data from a second workplace survey, the National Occupational 

Exposure Survey (NOES), conducted by NIOSH from 1981 to 1983, indicated that 27,208 workers, 

including 9,632 women, in 1,102 plants were potentially exposed to selenium in the workplace (NIOSH 

1983). The majority of these workers were employed in the health services (e.g., nursing), as janitors and 

cleaners, as machine operators, in the metals industry, or in work involving food and kindred products. 

These estimates were derived from observations of the actual use of selenium (87% of the total estimate) 

and the use of trade name products known to contain the selenium compounds (13%) (NIOSH 1989). 

Neither the NOHS database nor the NOES database contain information on the frequency, level, or 

duration of the exposure of workers to any of the chemicals listed therein. They are surveys that provide 

estimates of workers potentially exposed to the chemicals. 

The average selenium concentration in the blood of 20 workers employed in a rubber tire repair shop 

located in Mexico was 148 μg/L, while the average concentration in a control group of 18 healthy 

volunteers was 100 μg/L (Sánchez-Ocampo et al. 1996). Selenium was measured in the blood of 222 coal 

miners at concentrations ranging from 34.9–99.5 μg/L (Orszczyn et al. 1996). Selenium content in the 

blood decreased with age and unexpectedly, smokers had slightly lower blood plasma concentrations than 

nonsmokers. Furthermore, the most exposed miners (miners exposed to coal dust for more than 10 years) 
SELENIUM 278 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-6. Serum Selenium Concentrations (μg/L) in U.S. Population from 

NHANES III (DHHS 1997)a 

Sex and age n Populationb Mean SEM GM GM SE 

Both sexes 

All ages 18,292 192,615,658 124.75 0.47 123.63 0.44 

<6 years old 0 0 — — — — 

6–11 years old 0 0 — — — — 

12–19 years old 2,968 25,412,279 121.09 0.49 120.03 0.46 

20–59 years old 10,519 129,562,302 125.25 0.49 124.17 0.45 

60 years and older 4,905 37,641,076 125.48 0.55 124.26 0.54 

Males 

All ages 8,561 92,798,087 126.16 0.53 125.10 0.50 

<6 years old 0 0 — — — — 

6–11 years old 0 0 — — — — 

12–19 years old 1,330 12,835,980 121.46 0.58 120.57 0.57 

20–59 years old 4,839 63,886,151 127.22 0.56 126.17 0.52 

60 years and older 2,392 16,075,956 125.72 0.61 124.54 0.59 

Females 

All ages 9,731 99,817,571 123.43 0.45 122.29 0.43 

<6 years old 0 0 — — — — 

6–11 years old 0 0 — — — — 

12–19 years old 1,538 12,576,300 120.71 0.68 119.47 0.63 

20–59 years old 5,680 65,676,151 123.34 0.45 122.26 0.42 

60 years and older 2,513 21,565,120 125.30 0.58 124.04 0.57 

a

Data source: Third National Health and Nutrition Examination Survey (NHANES III), 1988–1994 (DHHS 1997). 

Data analysis: Syracuse Research Corporation, Syracuse, NY, using SUDAAN®

 and SAS®. b

Portion of the United States represented by the sample
 

GM = geometric mean; GM SE = standard error of the geometric mean; SEM = Standard error of the mean 
SELENIUM 279 

6. POTENTIAL FOR HUMAN EXPOSURE 

had lower selenium plasma levels than recently hired miners. Although the precise mechanism 

explaining the decrease in selenium concentration with dust exposure and smoking is unknown, the 

authors speculated that the decreased selenium levels might reflect its use by the increased demand in 

antioxidant protection, involving glutathione-peroxidase. Concentrations of selenium in the plasma and 

urine of copper refinery workers was studied (Rajotte et al. 1996). The levels of selenium in the urine and 

plasma of the 20 workers were 34.02–189.95 and 113.93–173.57 μg/L, respectively. The respective 

selenium levels in a control group that was not occupationally exposed were 26.71–118.39 μg/L and 

119.51–187.35 μg/L. 

6.6 EXPOSURES OF CHILDREN 

This section focuses on exposures from conception to maturity at 18 years in humans. Differences from 

adults in susceptibility to hazardous substances are discussed in 3.7 Children’s Susceptibility. 

Children are not small adults. A child’s exposure may differ from an adult’s exposure in many ways. 

Children drink more fluids, eat more food, breathe more air per kilogram of body weight, and have a 

larger skin surface in proportion to their body volume. A child’s diet often differs from that of adults. 

The developing human’s source of nutrition changes with age: from placental nourishment to breast milk 

or formula to the diet of older children who eat more of certain types of foods than adults. A child’s 

behavior and lifestyle also influence exposure. Children crawl on the floor, put things in their mouths, 

sometimes eat inappropriate things (such as dirt or paint chips), and spend more time outdoors. Children 

also are closer to the ground, and they do not use the judgment of adults to avoid hazards (NRC 1993). 

Children are exposed to selenium by the same pathways as adults. The primary route of exposure for 

children is through the ingestion of food sources. Selenium has been identified in pasteurized milk and 

milk-based infant formulas in the United States at mean concentrations in the range of 0.011–0.070 mg/kg 

(Table 6-4). Children may also be exposed to selenium by breast feeding mothers. Selenium was 

identified in the postpartum breast milk of women at different lactation stages at concentrations of 

6.1–53.4 μg/L (Li et al. 1999). Using these concentrations, the daily intake of selenium for fully breast 

fed infants was estimated to range from 5.2 to 17.9 μg/day. Others have reported the estimated daily 

dietary intake of selenium for infants as 20 μg/day, while the daily intake for adult males was estimated as 

120 μg/day (Pennington 1989). Selenium was detected in the umbilical blood of 350 subjects in the 

Czech Republic at concentrations of 4.0–82.6 μg/L (Černá et al. 1997). The concentration of selenium in 
SELENIUM 280 

6. POTENTIAL FOR HUMAN EXPOSURE 

the blood of 388 children (196 males, 192 females) ranged from 5.0 to 98.2 μg/L (Černá et al. 1997). 

Selenium was detected in fetal tissues at a mean concentration of 2.8 μg/g (Robkin et al. 1973). The 

concentration of selenium in various tissues of infants has been reported by Dickson and Tomlinson 

(1967) and is summarized in Table 3-6. In areas containing low (0.42 mg/kg), medium (3.09 mg/kg), and 

high (9.54 mg/kg) seleniferous soils, the mean whole blood selenium levels of school children 

(7–14 years of age) were 0.13, 0.37, and 1.57 mg/L, respectively (Yang et al. 1989b). Selenium was 

detected in postmortem liver, lung, and spleen samples of infants in Glasgow, Scotland at mean 

concentrations of 2.24, 0.76, and 0.099 ppm, respectively (Raie 1996). 

The tendency of young children to ingest soil, either intentionally through pica or unintentionally through 

hand-to-mouth activity, is well documented. This potential route of exposure is most likely in areas that 

naturally have high selenium content in soil. Since children often play in fields and soils, both dermal 

exposure and inhalation of dust particles from soil surfaces are possible. The soluble forms of selenium 

such as the inorganic alkali selenites and selenates are more likely to be bioavailable in soils than the 

relatively insoluble selenides. Children are not likely to be exposed to selenium from their parents’ work 

clothes, skin, hair, tools, or other objects removed from the workplace. Selenium is contained in some 

household products such as shampoos and preparations to treat dandruff and eczema (IARC 1975a). It is 

also contained in some dietary supplements (Goodman et al. 1990). Since it is unlikely that children 

would use these products without adult supervision, the potential for overexposure to selenium from these 

products is low, except for the possibility of accidental poisoning. 

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES 

Because selenium is a naturally occurring element found in rocks, soils, plants, and animals, the general 

population is commonly exposed to selenium through diet and drinking water. As a result of the uneven 

distribution of selenium in the earth's crust, populations living in certain areas of the United States are 

exposed to greater than average levels of selenium. Areas of the United States with highly seleniferous 

soils and plants include South Dakota, Wyoming, Montana, North Dakota, Nebraska, Kansas, Colorado, 

Utah, Arizona, and New Mexico (Valentine et al. 1978). Hawaii also has high levels of selenium in the 

soil, but not in plants (Smith et al. 1936; Valentine et al. 1978). Human exposure to selenium occurs 

through the ingestion of food (including meat, milk, eggs, and vegetables) and drinking water from these 

areas (Smith et al. 1936). Selenium was found at elevated levels in fish from rivers, creeks, and lakes in 

California, North Carolina, Texas, and Utah (RTI 1993). Farmers and fishermen living in these regions 
SELENIUM 281 

6. POTENTIAL FOR HUMAN EXPOSURE 

may be at higher risk of selenium exposure than people living in urban areas because farmers tend to 

consume a larger proportion of locally grown foods, and fishermen tend to consume seafood, whereas 

people in urban areas tend to consume foods grown over a wider geographic area. In addition, people 

who irrigate their home gardens with groundwater containing high selenium levels may grow and 

consume plants that contain high levels of selenium because this element accumulates in some plants. 

Fishermen and hunters of waterfowl who regularly consume fish and game from waterways with elevated 

selenium levels may increase their selenium body burden, but no reports of selenosis attributable to this 

practice have appeared in the literature. 

People living in the vicinity of hazardous waste sites or coal burning plants may also be exposed to high 

levels of selenium. Selenosis has been reported in residents of the Wudang Mountains, China where food 

was grown in highly seleniferous soil (Yang et al. 1989a, 1989b). Selenium blood levels of five patients 

with long persisting, distinct clinical signs of selenosis ranged from 1.054 to 1.854 mg/L (Yang et al. 

1989b). To attain selenium blood levels of this magnitude, it was estimated that the daily intake must be 

at least 910 μg/day. The mean selenium concentration in hair samples obtained from residents of a highly 

seleniferous region of Glasgow, Scotland was 18.92 ppm (Raie 1996). By comparison, the mean levels 

for adults from Iran and Iceland were only 5.72 and 1.81 ppm, respectively. 

6.8 ADEQUACY OF THE DATABASE 

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with the 

Administrator of EPA and agencies and programs of the Public Health Service) to assess whether 

adequate information on the health effects of selenium is available. Where adequate information is not 

available, ATSDR, in conjunction with the National Toxicology Program (NTP), is required to assure the 

initiation of a program of research designed to determine the health effects (and techniques for developing 

methods to determine such health effects) of selenium. 

The following categories of possible data needs have been identified by a joint team of scientists from 

ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that if met would 

reduce the uncertainties of human health assessment. This definition should not be interpreted to mean 

that all data needs discussed in this section must be filled. In the future, the identified data needs will be 

evaluated and prioritized, and a substance-specific research agenda will be proposed. 
SELENIUM 282 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.8.1 Identification of Data Needs 

Physical and Chemical Properties. The physical and chemical properties of elemental selenium 

and most of the common environmental forms of selenium have been characterized (Budavari et al. 1996; 

Lide 2000) and no further data are needed (see Chapter 4). 

Production, Import/Export, Use, Release, and Disposal. Knowledge of a chemical's production 

volume is important because it often correlates with possible environmental contamination and human 

exposure. Current data regarding the import (USGS 2002), export (USGS 2002), and use (Hoffmann and 

King 1997) of selenium are available. No statistics regarding the U.S. production of selenium have been 

reported since 1996 (USGS 2002). Current information on the U.S. production of selenium would assist 

in identifying potential exposures, particularly in regions of the country where environmental exposure to 

selenium through food and drinking water is already relatively high. 

According to the Emergency Planning and Community Right-to-Know Act of 1986, 42 U.S.C. 

Section 11023, industries are required to submit substance release and off-site transfer information to 

EPA. The Toxics Release Inventory (TRI), which contains this information for 2000, became available in 

May of 2002. This database will be updated yearly and should provide a list of industrial production 

facilities and emissions. 

Environmental Fate. Information is available to permit assessment of the environmental fate and 

transport of selenium in air (NAS 1976a), water (Chau and Riley 1965; NAS 1980b; Ohlendorf et al. 

1986a; Rudd and Turner 1983a; Saiki and Lowe 1987), and soil (Kabatas-Pendias and Pendias 1984, 

NAS 1976b). Selenium released to the air will be removed by wet and dry deposition. The forms of 

selenium expected to be found in surface water and the water contained in soils are the salts of selenic and 

selenious acids. Selenic acid (H2SeO4) is a strong acid. The soluble selenate salts of this acid are 

expected to occur in alkaline waters. Sodium selenate is one of the most mobile selenium compounds in 

the environment because of its high solubility and inability to adsorb onto soil particles (NAS 1976a). 

Selenious acid (H2SeO3) is a weak acid, and the diselenite ion predominates in waters between pH 3.5 and 

9. Most selenites are less soluble in water than the corresponding selenates (NAS 1980b). 

It has been suggested that a biological cycle exists for selenium (Shrift 1964), but certain components of 

the cycle remain uncharacterized. The biological transformation of selenide to elemental selenium has 

not been well described in the literature (see Maier et al. 1988). Further research on the biological 
SELENIUM 283 

6. POTENTIAL FOR HUMAN EXPOSURE 

selenium cycle might help to identify "hot spots" of selenium in the environment. For example, further 

investigation of parameters that influence the tendency of selenium to move from one medium to another 

(e.g., from soil to water) would improve fate and transport modeling efforts. 

Bioavailability from Environmental Media. The available monitoring data indicate that selenium 

is present in samples of air (Dams et al. 1970; Harrison et al. 1971; John et al. 1973; Peirson et al. 1973; 

Pillay et al. 1971), water (Besser et al. 1996; CRWQCB 1988; Cutter 1989; Glover et al. 1979; Lakin and 

Davidson 1967; Lewis 1988; Maier et al. 1988; NCDNR 1986; Oster et al. 1988a; Schutz and Turekiam 

1965; Smith and Westfall 1937), soil/sediment (Glover et al. 1979; Lemly 1997; Sindeeva 1964), human 

tissues (Li et al. 1999; Orszczyn et al. 1996; Yang et al. 1989a, 1989b), fish (Besser et al. 1996; Lowe et 

al. 1985; May and McKinney 1981; Ohlendorf et al. 1986b), and food (Beale et al. 1990; FDA 2000; 

Schubert et al.1987). Thus, it can be concluded that selenium is bioavailable from the environmental 

media. 

Food Chain Bioaccumulation. Selenium in food contributed to the highest proportion of the daily 

selenium intake for human populations in the United States. Fruits, vegetables, milk, meat, and grains 

contain very low levels of selenium. However, selenium is bioaccumulated by aquatic organisms (Chau 

and Riley 1965; Ohlendorf et al. 1986a; Rudd and Turner 1983a). Based on reported BCFs and BAFs 

(Lemly 1982, 1985), selenium is expected to bioaccumulate in fish. Some evidence indicates that under 

natural conditions, selenium might also biomagnify in aquatic organisms (Lemly 1985; Maier et al. 1988; 

NCDNR 1986; Sandholm et al. 1973). 

Exposure Levels in Environmental Media. Selenium has been detected in air (Dams et al. 1970; 

Harrison et al. 1971; John et al. 1973; Peirson et al. 1973; Pillay et al. 1971), water (CRWQCB 1988; 

Cutter 1989; Glover et al. 1979; Lakin and Davidson 1967; Lewis 1988; Maier et al. 1988; NCDNR 1986; 

Oster et al. 1988a; Schutz and Turekiam 1965; Smith and Westfall 1937), soil and sediment (Beath et al. 

1946; Coleman and Delevaux 1957; Glooschenko and Arafat 1988; Glover et al. 1979; Lemly 1997; NAS 

1976a; Rosenfeld and Beath 1964; Shamberger 1981; Sindeeva 1964), coal and oil (Hashimoto et al. 

1970; Pillay et al. 1969), plants (Arthur et al. 1992; Cappon 1981; Horne 1991; Rosenfeld and Beath 

1964; Shane et al. 1988), and food (Beale et al. 1990; FDA 2000; Schubert et al. 1987). Continued 

monitoring data of selenium levels in the environment are necessary to understand current exposure 

levels. 
SELENIUM 284 

6. POTENTIAL FOR HUMAN EXPOSURE 

Reliable monitoring data for the levels of selenium and selenium compounds in contaminated media at 

hazardous waste sites are needed. This information can be used in combination with the known body 

burden of selenium and selenium compounds to assess the potential risk of adverse health effects in 

populations living in the vicinity of hazardous waste sites. 

Exposure Levels in Humans. Selenium has been detected in the blood (Barceloux 1999; Orszczyn 

et al. 1996), urine (Gromadzinska et al. 1996), hair (Raie 1996; Yang et al. 1989a, 1989b), and nails 

(Yang et al. 1989a, 1989b) of exposed individuals. Various estimates of selenium intake for the U.S. 

populations have been reported (FDA 1982a; Levander 1987; Pennington et al. 1989; Schrauzer and 

White 1978; Schubert et al. 1987; Welsh et al. 1981). The largest numbers of exposed workers were 

heavy equipment mechanics, painters, mechanics, and special trade contractors (NOHS 1976). 

Preliminary data from another workplace study indicate that workplace exposure decreased from 1976 to 

1984 (NIOSH 1989). Continued monitoring data are necessary to understand and evaluate human 

exposures to selenium in both occupational and nonoccupational settings. 

Exposures of Children. Data are available regarding the exposure and body burdens of children to 

selenium. Children, like adults, are primarily exposed to selenium through the diet. In areas containing 

low (0.42 mg/kg), medium (3.09 mg/kg), and high (9.54 mg/kg) seleniferous soils, the mean whole blood 

selenium levels of school children (7–14 years of age) were 0.13, 0.37, and 1.57 mg/L, respectively (Yang 

et al. 1989b). Selenium was detected in postmortem liver, lung, and spleen samples of infants in 

Glasgow, Scotland at mean concentrations of 2.24, 0.76, and 0.099 ppm, respectively (Raie 1996). 

Children can be exposed to selenium from breast feeding mothers. Selenium was identified in the 

postpartum breast milk of women at different lactation stages at concentrations of 6.1–53.4 μg/L (Li et al. 

1999). Using these concentrations, the daily intake of selenium for fully breast fed infants was estimated 

to range from 5.2 to 17.9 μg/day. Others have reported the estimated daily dietary intake of selenium for 

infants as 20 μg/day, while the daily intake for adult males was estimated as 120 μg/day (Pennington 

1989). Since selenium is found in soil surfaces and children ingest soil either intentionally through pica 

or unintentionally through hand-to-mouth activity, pica is a unique exposure pathway for children. While 

selenium is found in some home products like shampoos (IARC 1975a) and dietary supplements 

(Goodman et al. 1990), this exposure route should be low and will not disproportionally affect children. 

Continued monitoring data are necessary to understand potentially dangerous routes of childhood 

exposure. 
SELENIUM 285 

6. POTENTIAL FOR HUMAN EXPOSURE 

Child health data needs relating to susceptibility are discussed in 3.12.2 Identification of Data Needs: 

Children’s Susceptibility. 

Exposure Registries. No exposure registries for selenium or selenium compounds were located. 

This substance is not currently one of the compounds for which a subregistry has been established in the 

National Exposure Registry. The substance will be considered in the future when chemical selection is 

made for subregistries to be established. The information that is amassed in the National Exposure 

Registry facilitates the epidemiological research needed to assess adverse health outcomes that may be 

related to exposure to this substance. 

The development of a registry of exposures would provide a useful reference tool in assessing exposure 

levels and frequencies. In addition, a registry developed on the basis of exposure sources would allow an 

assessment of the variations in exposure levels from one source to another and of the effect of 

geographical, seasonal, or regulatory actions on the level of exposure from a certain source. These 

assessments, in turn, would provide a better understanding of the needs for research or data acquisition 

based on the current exposure levels. 

6.8.2 Ongoing Studies 

A summary of some pertinent ongoing research related to selenium is reported. Federally sponsored 

research reported in the Federal Research in Progress (FEDRIP 2002) databases is shown in Table 6-7. 
SELENIUM 286 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-7. Ongoing Studies on the Environmental Effects of Seleniuma 

Investigator Affiliation Study Sponsor 

Finley JW 

Suarez DL, 

Amrhein C 

Baligar VC et al. 

Reddy KJ 

KpomblekouAdemawou K, 

Ankumah RO 

Doner HE 

Terry N 

Basta N 

Amrhein C 

Doner H, 

Amundson R 

Dudley LM et al. 

Logan TJ, 

Traina, SJ 

University of North Dakota 

(Grand Forks, North Dakota) 

University of California 

(Riverside, California) 

Virginia Polytechnical 

Institute and State University, 

(Blacksburg, Virginia) 

University of Wyoming, 

(Laramie, Wyoming) 

Tuskegee University, 

(Tuskegee, Alabama) 

University of California, 

(Berkeley, California) 

University of California, 

(Berkeley, California) 

Oklahoma State University 

(Stillwater, OK) 

University of California 

(Riverside, California) 

University of California, 

(Berkeley, California) 

Utah State University (Logan, 

Utah) 

Ohio State University 

(Columbus, Ohio) 

Chemical forms of selenium in foods 

Selenium and arsenic speciation and 

mobilization in irrigated soils and 

drainage waters 

Trace elements, chemistry, and plant 

uptake from soil applied coal byproducts/organic amendments 

Biogeochemistry and management of 

salts and potentially toxic trace 

elements in arid-zone soils, 

sediments and waters 

Trace elements in broiler littered soils: 

fate and effects on nitrogen 

transformation 

Factors controlling the distribution of 

trace elements in the solid-phase of 

terrestrial ecosystems 

Use of constructed wetlands in the 

bioremediation of selenium 

contaminated waters 

Chemistry and bioavailability of waste 

constituents in soils 

Biogeochemistry and management of 

salts and possible toxic trace 

elements in arid soils, sediments and 

waters 

Biogeochemistry and management of 

salts and potentially toxic trace 

elements in arid-zone soils, 

sediments and waters 

Biogeochemistry and Management of 

salts and potentially toxic elements in 

arid-zone soils sediments and water 

Chemistry and bioavailability of waste 

constituents in soils 

USDA 

USDA 

USDA 

USDA 

NRI 

Competitive 

Grant 

USDA 

USDA 

USDA 

USDA 

USDA 

USDA 

USDA 

a

Source: FEDRIP 2002 

NRI = National Research Institute; USDA = United Stated Department of Agriculture 
SELENIUM 287 

7. ANALYTICAL METHODS 

The purpose of this chapter is to describe the analytical methods that are available for detecting, 

measuring, and/or monitoring selenium, its metabolites, and other biomarkers of exposure and effect to 

selenium. The intent is not to provide an exhaustive list of analytical methods. Rather, the intention is to 

identify well-established methods that are used as the standard methods of analysis. Many of the 

analytical methods used for environmental samples are the methods approved by federal agencies and 

organizations such as EPA and the National Institute for Occupational Safety and Health (NIOSH). Other 

methods presented in this chapter are those that are approved by groups such as the Association of 

Official Analytical Chemists (AOAC) and the American Public Health Association (APHA). 

Additionally, analytical methods are included that modify previously used methods to obtain lower 

detection limits and/or to improve accuracy and precision. 

The analytical methods used to quantify selenium in biological and environmental samples are 

summarized below. Table 7-1 lists the applicable analytical methods used for determining selenium and 

selenium compounds in biological fluids and tissues, and Table 7-2 lists the methods used for determining 

selenium in environmental samples. 

7.1 BIOLOGICAL MATERIALS 

Sampling of biological material for determination of total selenium concentrations does not usually pose a 

problem unless specific selenium compounds are to be identified (Bem 1981). One exception is the 

collection and storage of urine samples without loss of volatile selenium compounds (Bem 1981). Unless 

special precautions are taken, most analyses of biological materials probably underestimate the 

concentration of these compounds. Ideally, selenium should be measured in 24-hour urine samples that 

have been stored in polyethylene containers in acid medium (Sanz Alaejos and Diaz Romero 1993). 

Blood samples should be separated into plasma or serum and cell fractions prior to freezing if the 

selenium levels in these components are to be measured separately. Freezing of biological samples 

immediately following collection is recommended to reduce enzymatic formation of volatile selenium 

compounds. 
SELENIUM	 288 

7. ANALYTICAL METHODS 

Table 7-1. Analytical Methods for Determining Selenium in Biological Materials 

Sample 

Sample Analytical detection Percent 

matrix	 Preparation method method limit recovery Reference 

Air (breath)	 Calibrate personal 

sampling pump; sample at 

a known flow rate for a 

total sample size of 

5–2,000 L; analyze at 

190.6 nm 

Blood Mineralize using HNO3­

HClO4 mixture, generate 

hydride, and atomize 

Digest blood sample with a 

nitric/perchloric acid 

mixture; fume mixture at 

200 EC and measure 

2,3-diaminonaphthalene 

Blood, Digest with Mg(NO3)2 or 

plasma, or HNO3 at a solution 

tissue temperature of 100 EC for 

homogenate	 60–90 minutes; add HCl; 

and add hydroxylamine 

sulfate, EDTA, and urea 

Serum	 Dilute sample with matrix 

modifier containing 

Mg(NO3)2 and Ni(NO3)2 to 

thermally stabilize Se; 

heat, dry, atomize; use 

Zeeman background 

correction 

Dilute sample with matrix 

modifier containing NiCl2; 

heat, dry, and atomize 

Nitric-perchloric acid 

digestion; HCl reduction; 

sodium borohydride 

reduction; measure 

selenium hydride 

On-line acid ashing of 

sample followed by 

hydrive generation 

ICP/AES 21 ng/mL 

HGAAS 1x10-8 g/g 

Fluorometric 1.2x10-9 g/g 

GC/ECD 1x10-8 g/g 

ZAAS No data 

GFAAS No data 

HGAAS No data 

ICP/AES 5.5 μg/L 

97–105%	 NIOSH 

1994a 

(method 

7300) 

No data Clinton 1977 

98%	 Rongpu et al. 

1986 

95–105%	 McCarthy et 

al. 1981 

6.2% Lewis et al. 

relative 1986b 

standard 

deviation 

84–116% Oster and 

Prellwitz 

1982 

33–73% Oster and 

Prellwitz 

1982 

98–106%	 Recknagel 

et al. 1993 
SELENIUM 289 

7. ANALYTICAL METHODS 

Table 7-1. Analytical Methods for Determining Selenium in Biological Materials 

Sample 

matrix Preparation method 

Analytical 

method 

Sample 

detection 

limit 

Percent 

recovery Reference 

Urine 24-hour samples analyzed 

to measure CT and 

Folin-Wu 

method for CT 

No data No data Hojo 1981b, 

1982 

selenium concentration in 

urine 

measurement; 

fluorimetric 

method to 

measure Se 

Digest sample with HNO3 

and HClO4 

Fluorometric No data 100±22% Koh and 

Benson 1983 

EAAS No data 4–8% Saeed 1986 

Add nitric acid, platinum, 

and nickel 

relative 

deviation 

Human 

spermatozoa 

and 

Digest with 25% 

tetramethylammonium 

hydroxide in methanol 

GFAAS 1x10-8 g/g 95.1±5.2% Suistomaa et 

al. 1987 

protasomes 

Biological 

samples 

Decompose sample with 

nitric acid; use 1,2-dibromobenzene as a reagent 

to measure piazselenol 

GC/ECD 1x10-9 g/g No data Shimoishi 

1977 

Spike sample with 82Se; 

digest; acidify with HCl; 

react with 

IDGC/MS 5x10-11 g/g No data Lewis 1988 

4-nitro-o-phenylenediamine; measure nitroLiver 

piazselenol 

Lyophilize sample; 

irradiate the sample; 

digest with HNO3, HClO4, 

and the carrier source; 

Radiochemical 

NAA 

2.2x10-10 g/g No data Lievens et al. 

1977 

distill sample, and use 

distillate for analysis 

Protein 

(human liver) 

INAA and gel 

filtration 

No data No data Norheim and 

Steinnes 

1975 

CT = creatinine; EAAS = electrothermal atomic absorption spectroscopy; EDTA = ethylenediaminetetraacetic acid; 

GC/ECD = gas chromatography/electron capture detection; GFAAS = graphite furnace atomic absorption spectroscopy; 

HCI = hydrochloric acid; HClO4 = perchloric acid; HGAAS = hydride generation atomic absorption spectroscopy; 

HNO3 = nitric acid; ICP/AES = inductively coupled plasma/atomic emission spectroscopy; IDGC/MS = isotope dilution 

gas chromatography/mass spectrometry; INAA = instrumental neutron activation analysis; Mg(NO3)2 = magnesium 

nitrate; NAA = neutron activation analysis; NiCl2 = nickel chloride; Se = selenium; ZAAS = graphite furnace atomic 

absorption spectroscopy with Zeeman background correction 
SELENIUM 290 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Selenium in 

Environmental Samples 

Sample 

matrix 

Food 

Preparation method 

Reduce selenium in 

sample from SeVI to 

SeIV; add zinc to the 

acidified sample; pass 

gaseous selenium 

hydride to AA 

Analytical 

method 

AA, 

gaseous 

hydride 

Sample 

detection 

limit 

2x10-9 g/mL 

Percent 

recovery 

100% 

Reference 

EPA 1979a 

(method 

270.3) 

Water 

Microwave digestion; 

acidify with HNO3 

Acidify sample with 

HCl, degas solution 

with N2 bubbling 

ICP-MS 

HGGC with 

photoionization 

detection 

No data 

1x10-12 g/mL 

(0.001 ppb) 

156% (fine 

flour); 149% 

milk powder) 

No data 

Zhou and Liu 

(1997) 

Vien and Fry 

1988 

Reduce selenium to 

SeIV with HCl and KBr; 

coprecipitate with 

lanthanum hydroxide; 

centrifuge. 

ICP/AES 0.06 μg/L 100% selenite; 

88% selenate 

Adkins et al. 

1995 

Acid digestion ICP/AES 21 ng/mL 97-105% NIOSH 

(2001) 

Water and 

waste water 

Water and 

wastes 

Acid digestion 

Acid digestion 

AA, furnace 

AA, furnace 

2x10-9 g/mL 

5x10-9 g/mL 

94–112% 

No data 

EPA 1979a 

(method 

270.2) 

EPA 1984b 

(method 

200.7 CLP-M) 

Solid/solid 

waste/sludge 

Aqueous samples 

subject to acid 

digestion 

AA, furnace 2x10-9 g/mL No data EPA 1984c 

(method 

7740) 

Acid digestion; 

measure at 196 mm 

ICP and 

GFAAS 

7.5x10-8 g/mL 94–112% EPA 1986c 

(methods 

3050, 6010) 

Acid digestion with 

HNO3/sulfuric acid; 

convert SeIV to volatile 

hydride 

AA, 

gaseous 

hydride 

2x10-9 g/mL 100% EPA 1997a 

(method 

7741a) 

Acid digestion AA, furnace 2x10-9 g/mL No data EPA 1984b 

(method 

270.2 CLP-M) 
SELENIUM 291 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Selenium in 

Environmental Samples 

Sample 

Sample Analytical detection Percent 

matrix Preparation method method limit recovery Reference 

Wastes/soil/ Nitric acid digestion or AA, furnace 3x10-9 g/mL 100.5 % EPA 1997b 

groundwater nitric/peroxide/hydrochl (method 

oric acid digestion 7742) 

Organic Oxidize organic Cathodic 5x10-9 g/mL No data DOE 1987 

waste samples, absorb stripping 

combustion products in 

NaOH; separate on an 

ion exchange column 

Digest aqueous 

sample with HNO3 and 

perchloric acid 

Marine Decompose tissue HGAAS 2x10-7 g/g No data Welz and 

biological sample with HNO3 Melcher 1985 

tissues under pressure; add 

sulfuric and perchloric 

acids; heat at 310 EC 

to evaporate excess 

acid; add HCl 

Marine Digest sample with HGAES-ICP 5x10-9 g/mL No data DOE 1987 

samples concentrated HNO3 at 

room temperature; add 

HNO3, perchloric, and 

sulfuric acids to 

complete digestion; 

evaporate extra acids; 

dissolve residue in HCl 

Avian eggs Digest sample with GFAAS 4x10-7 g/g No data Krynitsky 

and liver HNO3; and hydrogen 1987 

peroxide to increase 

solubility 

Fat materials Melt butter under an HGAAS 10 ppb No data Narasaski 

(butter) infrared lamp; digest 1985 

with HNO3, sulfuric, 

and perchloric acids 
SELENIUM 292 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Selenium in 

Environmental Samples 

Sample 

matrix Preparation method 

Analytical 

method 

Sample 

detection 

limit 

Percent 

recovery Reference 

Plants Gravimetric 

method 

2x10-6 g/g No data AOAC 1984 

(method 

3.101) 

Grind air-dried or fresh 

samples; acid digest 

with HNO3 and HCl 

Fluorometric 

method 

<4x10-6 g/g No data AOAC 1984 

(method 

3.102 to 

add EDTA; neutralize 

with NH4OH; add HCl; 

3.107) 

shake with decalin; 

centrifuge decalin 

layer; read decalin 

solution with 

fluorometer at 525 nm 

within 5 minutes 

Food Digest sample with 

HNO3, perchloric, and 

sulfuric acids; heat; 

Titrimetric 

method 

No data No data AOAC 1984 

(methods 

25.154 and 

add H2O2; mix with 

EDTA, NH4OH, and 

25.158) 

DAN; boil; add 

cyclohexane and 

shake; read 

cyclohexane layer at 

525 nm 

Air 

(particulate) 

Fileter particulate 

matter from air; 

irradiate and count 

NAA, nondestructive 1x10-10 g/m3 No data Dams et al. 

1984 

sample 

Air Calibrate sampling 

pump; sample at a 

known flow rate for a 

total sample size of 

13–2,000 L; analyze at 

190.6 nm 

ICP/AES 21 ng/mL 97–105% NIOSH 1994a 

(method 

7300) 

AA = atomic absorption; AES = atomic emission spectrometry; CFAAS = graphite furnace atomic absorption 

spectroscopy; DAN = 2,3-diaminonaphthalene; EDTA = ethylenediamine tetraacetate; HCl = hydrochloric acid; 

HGAAS = hydride generation atomic absorption spectroscopy; HGAES = hydride generation atomic emission 

spectroscopy; HGGC = hydride generation gas chromatography; HNO3 = nitric acid; ICP = inductively coupled plasma; 

KBr = potassium bromide; N2 = nitrogen; NAA = neutron activation analysis; NaOH = sodium hydroxide; 

NH4OH = ammonium hydroxide
 
SELENIUM 293 

7. ANALYTICAL METHODS 

A variety of analytical methods can be used to determine trace concentrations (ng/g) of selenium in 

biological tissues. These include fluorometry, neutron activation analysis (NAA), atomic absorption 

spectroscopy (AAS), inductively coupled plasma-atomic emission spectroscopy (ICP-AES), inductively 

coupled plasma-mass spectrometry (ICP-MS), gas chromatography (GC), spectrophotometry, x-ray 

fluorescence analysis, and others. 

Classical flame AAS techniques do not have sufficiently low detection limits for selenium to be useful for 

determining its presence in biological samples (Koirtyohann and Morris 1986). Hydride generation 

atomic absorption spectroscopy (HGAAS) has been used instead for determination of selenium in 

biological samples such as blood and blood constituents and meat, fruits, and vegetables (Bem 1981). 

Graphite furnace atomic absorption spectroscopy (GFAAS) offers high sensitivity (5x10-11 g selenium/g 

sample), but interference from the matrix can cause significant difficulties (Lewis 1988). GFAAS 

methods rely on the fact that numerous metal compounds react with selenium compounds to form 

relatively refractory metal selenides (Oster and Prellwitz 1982). Nickel, molybdenum, and platinum are 

commonly added to the sample to thermally stabilize the selenium. Organic materials are then destroyed 

by high temperature in the furnace prior to atomization of the sample at very high temperatures (e.g., 

2,700 EC) (Oster and Prellwitz 1982). One advantage of GFAAS techniques is that the material in the 

graphite sample cell can be chemically treated in situ to reduce chemical interference. GFAAS 

techniques require correction for background absorption. Correction techniques include the deuterium 

continuum light source method (Hoenig and Van Hoeyweghen 1986) and the Zeeman splitting of the 

absorption line (Koirtyohann and Morris 1986). A Zeeman-effect system, which applies a magnetic field 

to the atomizer, allows the background correction to be performed at the exact analyte wavelength 

without the use of auxiliary light sources (Fernandez and Giddings 1982). The Zeeman-effect 

background correction is necessary for the determination of selenium in blood and blood products when 

GFAAS is used because a spectral interference from iron occurs at the selenium wavelength that cannot 

be corrected by a deuterium continuum source. 

A modification of the GFAAS method for determining selenium levels in human urine was described by 

Saeed (1986). In this electrothermal atomic absorption spectrometry (EAAS) method, nitric acid, nickel, 

and platinum are added to the graphite cell. The addition of nickel helps to mask the spectral interference 

from phosphates in urine. EAAS has been used to determine selenium levels in human spermatozoa 

(Suistomaa et al. 1987). For human blood plasma and serum, the detection limit of the EAAS method 
SELENIUM 294 

7. ANALYTICAL METHODS 

was 0.8 μg/L (2 ng absolute), with recoveries of 87–96% for plasma and 94–104% for serum (Harrison et 

al. 1996). 

HGAAS offers reduced chemical interference but requires larger sample volumes than GFAAS 

techniques (Koirtyohann and Morris 1986). HGAAS techniques have been used to measure selenium 

concentrations in food (Fiorino et al. 1976). These techniques use wet-sample digestion (e.g., nitricperchloric acid) to destroy organic matter. Sample reduction to convert Se(VI) (+6 valence state) to 

Se(IV) (+4 valence state) is necessary prior to using sodium borohydride to reduce all selenium present to 

selenium hydride (Macpherson et al. 1988). The selenium hydride is thermally decomposed and atomized 

in the sample beam of the atomic absorption spectrophotometer. Nitric-perchloric acid is commonly used 

for the digestion step. Because perchloric acid is potentially explosive, use of phosphoric acid instead is 

also common. Following the International Union of Pure and Applied Chemists (IUPAC) interlaboratory 

trial for the determination of selenium in human body fluids, Welz and Verlinden (1986) reported that it 

was important to use a temperature of at least 200 oC for sample decomposition when using HGAAS. 

They attributed the severe imprecision and systematic errors in measuring selenium in multiple samples to 

improper sample decomposition. Norheim and Haugen (1986) demonstrated that a combined system of a 

wet digestion and an automated hydride generator could analyze approximately 80 samples per day. 

ICP-AES with hydride vapor generation has been used to determine total selenium in biological samples 

(Tracy and Moller 1990). This technique is especially suited to the analysis of small samples. Samples 

are wet ashed with nitric, sulfuric, and perchloric acids at temperatures up to 310 oC. After treatment with 

hydrochloric acid, selenium is reduced by sodium borohydride to hydrogen selenide in a simplified 

continuous flow manifold. A standard pneumatic nebulizer affects the gas-liquid separation of H2Se, 

which is quantified by ICP-AES at 196.090 nm. The instrument detection limit for this method has been 

determined to be 0.4 μg/L 

Hydride generation atomic fluorescence spectrometry (HGAFS) has been used to measure selenium 

concentrations in urine (Sabé et al. 2001). Samples were completely mineralized using a focused 

microwave oven with a mixture of nitric acid and sulfuric acid for 14 minutes. Complete recovery was 

achieved from selenocystine (SeCys), selenomethionine (SeMet), and trimethyl selenium (TMeSe) 

species. The detection and limit of quantization for this method were 57 and 190 pg selenium/L. 

Application of gas-liquid chromatography (GLC) to determine selenium in biological samples allows for 

the elimination of interference from the biological matrix. GLC requires prior decomposition of organic 
SELENIUM 295 

7. ANALYTICAL METHODS 

matter with nitric acid. GLC techniques are based on measurement of the amount of piazselenol formed 

by the reaction of selenium (IV) with appropriate reagents in acidic media (Bem 1981). For gas 

chromatographic determination of selenium with an electron capture detector, 1,2-diaminoarenes can be 

used as reagents to produce piazselenols (McCarthy et al. 1981; Poole et al. 1977; Shimoishi 1977; 

Young and Christian 1973). Using 1,2-diamino-3,5-dibromobenzene as a reagent, Shimoishi (1977) 

obtained a detection limit of 1x10-9 g selenium per gram of sample. 

Isotope dilution gas chromatography/mass spectrometry (IDGC/MS) is a highly accurate technique that is 

more accessible than NAA techniques. IDGC/MS has been used to determine selenium in foods, plasma 

and serum, red blood cells, feces, urine, and human breast milk (Lewis 1988). The minimum sample size 

per determination is 0.5–10 g (0.5–10 mL). In the IDGC/MS method, a stable selenium isotope is added 

to the sample prior to digestion. This procedure eliminates the need for quantitative sample preparation 

and external standardization (Lewis 1988). However, a disadvantage of this technique is that enriched 

isotopic standards are expensive. 

NAA techniques provide lower detection limits for selenium (between 10-8 and 10-9 g selenium per gram 

of sample), but there are few reactors at which NAA facilities and expertise are available (Koirtyohann 

and Morris 1986). The most common NAA procedure for selenium determination is to produce the longlived 75Se radionuclide (half-life of 119 days) and count the samples after a 50–100-hour irradiation 

period and a 2–10-week cooling period. A faster NAA technique utilizes metastable 77mSe, which has a 

much shorter half-life (17.4 seconds), so that counting can be initiated after an irradiation and cooling 

period of <1 minute (Koirtyohann and Morris 1986). The most common standard reference sample for 

NAA techniques is bovine liver tissue (Bem 1981). Biological tissues that can be analyzed for selenium 

using the NAA technique include bone, hair, liver, kidney, lung, serum, blood, feces, urine, brain, 

stomach, skin, aorta, heart, testis, pituitary gland, tooth enamel, tongue, muscle, spleen, and thyroid 

(Yukawa et al. 1980). For many NAA techniques, destructive sample pretreatment (involving 

radiochemical separation) is required to avoid interference from the biological matrix (Koirtyohann and 

Morris 1986). The advantages of NAA are its low detection limits and multielement capability (Molokhia 

et al. 1979). Because facilities at which NAA can be performed are extremely limited, NAA's most 

useful application is as a reference method against which other less expensive and more common methods 

can be compared for accuracy. 

Spectrophotometric, fluorometric, voltammetric, and x-ray fluorescence analysis methods have also been 

successfully employed to determine selenium levels in blood, tissue, and human hair. Of these, 
SELENIUM 296 

7. ANALYTICAL METHODS 

fluorometric methods are most commonly used (Koh and Benson 1983). The reaction of selenium(VI) 

with 2,3-diaminonaphthalene (DAN) or with 3,3-diaminobenzidine (DAB) to form a fluorescent Se-DAN 

or Se-DAB heterocyclic compound is the basis of the fluorometric method of selenium determination 

(Allaway and Cary 1964; Chen et al. 1982; Lewis 1988). The piazselenol formed with DAN as the 

reagent has greater fluorescence sensitivity than the piazselenol formed with DAB as the reagent and is 

also extractable into organic solvents from acid solution (Chen et al. 1982). Fluorometric techniques 

require sample digestion to destroy organic matter and sample reduction to convert the selenium to the 

selenium(IV) oxidation state (Macpherson et al. 1988). Loss of volatile selenium compounds is possible 

during sample digestion and manipulation because several steps are required. Chen et al. (1982), 

Hasunuma et al. (1982), and Koh and Benson (1983) developed modifications of the digestion and 

treatment steps for selenium determination by fluorometric methods. Their methods allow small sample 

sizes, can be performed in a single flask, and measure submicrogram amounts of selenium. 

Some of the methods for determining selenium in biological materials have been compared within the 

same laboratory for accuracy and precision. Macpherson et al. (1988) compared the accuracy of three 

methods for the determination of selenium in biological fluid samples from biological materials with 

certified selenium levels. Acid decomposition fluorometry, HGAAS, and EAAS gave equally accurate 

results. Lewis et al. (1986) compared the graphite furnace atomic absorption spectrometry with the 

Zeeman-effect background correction (ZAAS) to isotope dilution mass spectrometry (IDMS) for 

determination of selenium in plasma and concluded that the ZAAS method compared favorably 

(correlation coefficient 0.987), but was half as precise as the IDMS method. Oster and Prellwitz (1982) 

compared HGAAS and GFAAS for the determination of selenium in serum. They concluded that the two 

techniques exhibited approximately equal detection limits in their laboratory. 

In three studies that compared analytical methods for the detection of selenium in biological samples, all 

found that fluorometry gave both accurate and reliable results (Burguera et al. 1990; Heydorn and 

Griepink 1990; Macpherson et al. 1988). Burguera et al. (1990) indicated the acceptance of HGAAS as 

yielding reliable results, whereas Heydorn and Griepink (1990) reported HGAAS had a high relative 

standard deviation of 11.4%. 

Decomposition procedures have been improved and analytical methods have been modified in recent 

years to increase the accuracy and speed of determination of selenium concentrations in plasma, serum, 

and urine. Reamer and Veillon (1983) used phosphoric acid along with nitric acid and hydrogen peroxide 

in digestion of biological fluids instead of perchloric acid to prepare samples for fluorometry. They 
SELENIUM 297 

7. ANALYTICAL METHODS 

concluded that phosphoric acid digestion increases the safety and convenience of the determination. 

Krynitsky (1987) used a modified wet digestion method for the determination of selenium in biological 

samples such as eggs and liver of avian species. This method uses hydrogen peroxide to enhance the 

solubility of the sample. Digestion with HNO3 and HClO4 is essential for accurate analysis of the total 

selenium in urine to ensure complete oxidation of the trimethylselenonium ion (Koh and Benson 1983). 

7.2 ENVIRONMENTAL SAMPLES 

Many of the basic analytical methods used for determining selenium in biological media are also used for 

determining selenium levels in soil, water, and air. Precautions in the collection and storage of 

environmental samples, however, are necessary to prevent loss of the volatile selenium compounds to the 

air. The destruction of organic matter before selenium measurement is also often necessary. 

Acidification of water samples to a pH of 1.5 is recommended to preserve selenium compounds (MuZoz 

Olivas et al. 1994). Nitric acid can be used, although it interferes with the hydride generation method of 

analysis. The best storage method for selenium compounds in water is in glass containers at 4 EC 

(Wiedmeyer and May 1993). 

The analytic methods generally fall into two groups: (1) those that do not require the destruction of 

organic materials in the sample and (2) those that require the elimination of interfering matter before the 

selenium content can be measured. X-ray fluorescence and some of the neutron activation analysis 

techniques do not require sample destruction, whereas spectrophotometry, GC, atomic absorption 

spectrometry, polarography, titration, spark source, MS, fluorometry, and other neutron activation 

analysis techniques require some degree of sample destruction. Fluorometry, atomic absorption 

spectrometry, and neutron activation analysis are the most frequently used methods. 

Inductively coupled plasma (ICP) emission techniques can be used to measure selenium concentrations. 

ICP techniques offer multielement capabilities, but instrumentation is costly and background interference 

can be a problem (Koirtyohann and Morris 1986). The NIOSH-recommended method for determining 

selenium in air is inductively coupled argon plasma atomic emission spectroscopy (NIOSH 1994a). 

Selenium may be measured in water following NIOSH Method 7300. The limit of detection for this 

method is 21 ng/mL using a selenium emission line at 190.6 nm (NIOSH 2001). ICP-MS has been used 

to determine the concentration of selenium in cloud water at detection limits of 100 and 25 pg/mL using 

pneumatic and ultrasonic nebulization, respectively (Richter et al. 1998). 
SELENIUM 298 

7. ANALYTICAL METHODS 

AAS techniques are commonly used for the determination of selenium in environmental samples. 

Hydride generation AAS is more sensitive than flame or graphite furnace AAS for the determination of 

selenium in materials of variable composition. Water samples, including freshwater, river water, sea 

water, and surface waters, and industrial wastes, muds, sediments, and soil samples have been analyzed 

by AAS techniques to detect selenium at parts-per-trillion levels (Bem 1981). Selenium(VI) and 

selenium(IV) can be distinguished in water samples with GFAAS by selective extraction procedures. 

HGAAS can also be used to distinguish between selenium(VI) and selenium(IV) in environmental 

samples because selenium(VI) does not readily form the hydride without reduction (Koirtyohann and 

Morris 1986). Selenium(VI) is calculated on the basis of the total selenium minus selenium(IV) (Bem 

1981). 

NAA has been used to determine selenium levels in environmental samples. Dams et al. (1970) reported 

a detection limit of 1x10-10 g/m3

 selenium using nondestructive NAA for determining selenium in air 

particulate matter. For determining selenium levels in soil, radiochemical variants of NAA have been 

commonly employed (Bem 1981). Instrumental neutron activation analysis (INAA) is frequently used to 

determine selenium concentrations in water and can also be used to distinguish between selenium(IV) and 

selenium(VI) oxidation states (Bem 1981). INAA is also used to determine selenium concentrations in air 

(Bem 1981). 

Gas liquid chromatography allows for elimination of interference from the matrix when analyzing 

environmental samples. When analyzing biological samples, a variety of reagents can be used to convert 

selenium to piazselenols for measurement with an electron capture detector. Spectrophotometric 

determinations of selenium are performed using organic reagents, whereas fluorometric analysis relies on 

piazselenol fluorescence to measure submicrogram levels of the element. 

The hydride generation GC with photoionization detection (HGGC-PD) method for selenium 

determination was developed by Vien and Fry (1988). The combined usage of a photoionization detector 

and a cold trap provided at least two orders of magnitude improvement in detectability over the existing 

GC systems. The detection limit for the HGGC-PD method was 1x10-12 g selenium/mL (0.001 ppb) for 

28 mL samples. An advantage of the HGGC-PD technique is the ability to perform simultaneous 

determinations of at least four different hydride-forming elements (Vien and Fry 1988). 
SELENIUM 299 

7. ANALYTICAL METHODS 

EPA's Contract Laboratory Program (EPA 1984b) requires the participating laboratories to meet the 

Contract Required Detection Level (CRDL) for selenium of 5x10-9 g selenium/mL (5 μg selenium/L) 

using proven instruments and approved analytical techniques, including ICP and atomic absorption 

methods. 

7.3 ADEQUACY OF THE DATABASE 

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with the 

Administrator of EPA and agencies and programs of the Public Health Service) to assess whether 

adequate information on the health effects of selenium is available. Where adequate information is not 

available, ATSDR, in conjunction with the National Toxicology Program (NTP), is required to assure the 

initiation of a program of research designed to determine the health effects (and techniques for developing 

methods to determine such health effects) of selenium. 

The following categories of possible data needs have been identified by a joint team of scientists from 

ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that if met would 

reduce the uncertainties of human health assessment. This definition should not be interpreted to mean 

that all data needs discussed in this section must be filled. In the future, the identified data needs will be 

evaluated and prioritized, and a substance-specific research agenda will be proposed. 

7.3.1 Identification of Data Needs 

Methods for Determining Biomarkers of Exposure and Effect. 

Exposure. Methods that distinguish among the various selenium compounds are not commonly used to 

estimate human exposure to selenium, but have been used in specialized metabolic studies. Analytical 

methods currently used to measure concentrations of selenium in biological fluids or human tissue 

samples as an indication of human exposure are described in Table 7-1. Attempts to use measures of 

whole blood GPX activity levels as indicators of human exposure to selenium have not been successful. 

Errors can result if the selenium-dependent GPX activity is not distinguished from the nonseleniumdependent GPX activity (Edwards and Blackburn 1986). In addition, whole blood selenium 

concentrations and GPX activity appear to correlate with one another only at low blood selenium levels 

(<0.100 mg selenium/L) (Allaway et al. 1968; Valentine et al. 1980). GPX activity levels measured in 
SELENIUM 300 

7. ANALYTICAL METHODS 

platelets have provided an indication of selenium exposure levels at low blood selenium levels (NPve et 

al. 1988). Whether platelet GPX activity levels would provide an indication of selenium status in 

populations with plasma selenium levels above 0.012 mg selenium/L is not known. There is great 

variability in the exposure data available for humans. Therefore, until larger databases of selenium 

concentrations in biological materials from affected and unaffected populations are available, no 

recommendations for analytical methods can be made. 

Effect. There are no known sensitive and specific biomarkers of effect for selenium. Therefore, no 

analytical methods recommendations can be made for biomarkers of effect for selenium, at the present 

time. 

Methods for Determining Parent Compounds and Degradation Products in Environmental 

Media. Numerous analytical methods are available for the determination of selenium levels in 

environmental media (AOAC 1984; Bem 1981; Dams et al. 1970; DOE 1987; EPA 1984b, 1986c; 

Koirtyohann and Morris 1986; NIOSH 1994a; Vien and Fry 1988). However, most of these do not 

distinguish among the various selenium compounds. Many of the available methods can be used to detect 

selenium at subnanogram levels. For the determination of selenium only, fluorometry, chromatography, 

or spectrometry are the preferred techniques. When conducting a multielemental analysis or when 

analyzing a complex matrix, more sophisticated methods are required. 

It is possible to detect selenium levels as low as 1 ng/m3

 of air using neutron activation analysis. 

Standardized methods for selenium determination in different environmental samples such as water, soil, 

sludge, and industrial waste are available in the above-mentioned literature. 

There are fewer methods available for distinguishing among the inorganic forms of selenium in the 

environment. HGAAS, INAA, and GFAAS with selective extraction procedures can be used to 

distinguish between selenium(VI) and selenium(IV) in samples of soil and water. Methods for 

determining selenium sulfide levels in the environment are lacking, but would be useful for the 

identification and measurement of this potentially carcinogenic selenium compound. 

Very limited information is available regarding the sensitivity, reliability, and specificity of the existing 

methods. Further studies to determine these factors would be useful. 
SELENIUM 301 

7. ANALYTICAL METHODS 

7.3.2 Ongoing Studies 

N.J. Miller-Ihli and coworkers at the Agricultural Research Service (Beltsville, Maryland) are conducting 

studies to develop single and multielement methods for the determination of trace elements of nutritional 

and health concern (e.g., selenium). Some techniques proposed in their studies include: GFAAS and 

electrothermal vaporization inductively coupled plasma-mass spectrometry (ICP-MS); inductively 

coupled plasma-atomic emission spectrometry (ICP-AES); electrothermal vaporization ICP-MS (USSETV-ICP-MS) and USS-GFAAS; and capillary zone electrophoresis (CZE) coupled with ICP-MS 

(FEDRIP 2002). 

SELENIUM 303 

8. REGULATIONS AND ADVISORIES 

Because of its potential to cause adverse health effects in exposed people, a number of regulations and 

guidelines have been established for selenium by various national and state agencies. These values are 

summarized in Table 8-1. 

The current Recommended Dietary Allowances (RDAs) for selenium, established by the Food and 

Nutrition Board of the National Research Council (National Academy of Sciences) (NAS 2000), are listed 

below. The recommended Tolerable Upper Intake Level (UL) for selenium in adults is 0.4 mg/day (NAS 

2000). The UL is defined as the highest level of daily nutrient intake that is likely to pose no risk of 

adverse health effects to almost all individuals in the general population. 

Men: 0.055 mg/day
 

Women: 0.055 mg/day
 

Pregnant women: 0.060 mg/day
 

Lactating women: 0.070 mg/day
 

Infants (0–6 months): 0.015 mg/day
 

Infants (7–12 months): 0.020 mg/day
 

Children (1–3 years): 0.020 mg/day
 

Children (4–8 years): 0.030 mg/day
 

Children (9–18 years): 0.040 mg/day
 

A chronic oral MRL of 0.005 mg/kg/day was derived for selenium based on a NOAEL of 

0.015 mg/kg/day for disappearance of symptoms of selenosis in recovering individuals (Yang and Zhou 

1994), as discussed in Section 2.3. The NOAEL was divided by an uncertainty factor of three to account 

for sensitive individuals. The EPA used the same human NOAEL for clinical selenosis 

(0.015 mg/kg/day) (Yang et al. 1989a, 1989b) and an uncertainty factor of three to derive a chronic oral 

reference dose (RfD) of 0.005 mg/kg/day for selenium (EPA 2003). 
SELENIUM 

8. REGULATIONS AND ADVISORIES 

304 

Agency 

Table 8-1. Regulations and Guidelines Applicable to Selenium 

Description Information References 

INTERNATIONAL 

Guidelines: 

IARC Carcinogenicity classification 

WHO Guideline for drinking water 

Recommended daily intake for 

adults 

NATIONAL 

Regulations and 

Guidelines: 

a. Air 

ACGIH TLV (8-hour TWA) 

Selenium and compounds 

 Selenium hexafluoride 

EPA Hazard rank under Section 112(g) of 

the Clean Air Act Amendments 

Reference air concentration 

NIOSH REL (TWA) 

Selenium and compounds, 

except selenium hexafluoride 

IDLH 

Selenium and compounds 

OSHA General industry PEL (TWA) 

Selenium and compounds 

 Selenium hexafluoride 

 Hydrogen selenide 

Construction industry PEL (TWA) 

Selenium and compounds 

 Selenium hexafluoride 

b. Water 

EPA MCLG 

MCL 

DWEL 

Health advisory—lifetime 

Groundwater monitoring (PQL) 

 Groundwater monitoring— 

concentration limits 

Group 3a

 IARC 2001 

0.01 mg/L WHO 2001 

0.9 μg/kg body 

weight 

ACGIH 2000

0.2 mg/m3 

0.16 mg/m3 

42 out of 1–100, with EPA 2001a 

100 being the most 

toxic 

3.0 μg/m3

 EPA 2001b 

40CFR 266, 

Appendix IV 

NIOSH 2001 

0.2 mg/m3 

1.0 mg/m3 

OSHA 2001 

0.2 mg/m3	 29CFR1910.1000, 

0.4 mg/m3	 Table Z 

0.2 mg/m3 

OSHA 2001 

0.2 mg/m3 

0.16 mg/m3 

0.05 mg/L EPA 2001c 

40CFR141.51 

0.05 mg/L EPA 2001d 

40CFR141.62 

0.2 mg/L EPA 2000 

0.05 mg/L 

750 μg/L EPA 2001e 

40CFR264, 

Appendix IX 

0.01 mg/L EPA 2001f 

40CFR264.94 
SELENIUM 305 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Selenium 

Agency Description Information 

NATIONAL (cont.) 

References 

EPA Water quality standards EPA 2001g 

 Freshwater 40CFR131.36 

Maximum concentration 20 μg/L 

Continuous concentration

 Saltwater 

5.0 μg/L 

Maximum concentration 290 μg/L 

Continuous concentration 

c. Food 

71 μg/L 

FDA Approved use of selenium as a food ≤0.3 ppm FDA 2001a 

additive in animal feeds—added to 

feed for chickens, swine, turkeys, 

21CFR573.920 

sheep, cattle, and ducks 

Bottled water—allowable level 0.05 mg/L FDA 2001b 

21CFR165.110 

 RDA (mg/day) NAS 2000 

Men 0.055 

 Women 0.055 

 Pregnant women 0.060 

 Lactating women 0.070 

 Infants (0–6 months) 0.015 

 Infants (7–12 months) 0.020 

 Children (1–3 years) 0.020 

 Children (4–8 years) 0.030 

 Children (9–18 years) 

d. Other 

0.040 

EPA Carcinogenicity classification IRIS 2001 

Selenium and compounds 

 Selenium sulfide 

Group Db 

Group B2c 

Designation of hazardous EPA 2001h 

substances

 Selenium oxide 

40CFR116.4 

 Sodium selenite 

Determination of reportable EPA 2001i 

quantities 40CFR117.3 

 Selenium oxide 10 pounds 

 Sodium selenite 100 pounds 

Extremely hazardous substance EPA 2001j 

40CFR355, 

Reportable quantity Appendix B 

 Hydrogen selenide 10 pounds 

 Selenious acid 10 pounds 

 Selenium oxychloride 500 pounds 

Threshold planning quantity 

 Hydrogen selenide 10 pounds 

 Selenious acid 1,000/10,000 pounds 

 Selenium oxychloride 500 pounds 
SELENIUM	 306 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Selenium 

Agency Description Information References 

NATIONAL (cont.) 

EPA Identification and listing of 

hazardous waste 

Selenium 

Selenium and compounds 

 Selenium dioxide 

 Selenium sulfide 

Selenium tetrakis, (dimethyl- 

 dithiocarbamate) 

 Selenious acid 

 Selenourea 

 Thallium selenite 

Protection standards at inactive 

uranium processing sites—listed 

constituents 

Selenium and compounds 

 Selenium dioxide 

 Selenium sulfide 

Recommended daily allowances 

Selenium and compounds 

Men 

Women 

Infants 

 Reportable quantity 

Selenium and compounds 

 Selenium dioxide 

 Selenium sulfide 

 Selenious acid 

 Selenourea 

 Sodium selenite 

 Thallium selenite 

 Reportable quantity 

 Selenium oxide 

Sewer sludge—disposal or use 

standards

 Ceiling concentration 

Cumulative pollutant loading 

rate 

 Pollutant concentrationd 

Annual pollutant loading rate 

Toxic chemical release reporting; 

Community Right-to-Know; effective 

date 

STATE 

Regulations and 

Guidelines: 

a. Air 

 Hawaii HAP 

 EPA 2001k 

40CFR261, 

Appendix VIII 

 EPA 2001l 

40CFR192, 

Appendix I 

EPA 2001m 

0.7x10-1 mg/kg/day 

0.55x10-1 mg/kg/day 

8.7x10-4 mg/kg/day 

EPA 2001n 

1 pound 40CFR302.4, 

1,000 pounds Appendix A 

1 pound 

1 pound 

1 pound 

1,000 pounds 

1 pound 

EPA 2001o 

10 pounds 40CFR117.3 

EPA 2001p 

40CFR503.13 

100 mg/kg 

100 kg/hectare 

100 mg/kg 

5.0 kg/hectare per 

365-day period 

01/01/87 EPA 2001q 

40CFR372.65 

BNA 2001 
SELENIUM	 307
 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Selenium 

Agency Description Information References 

STATE (cont.)
 

Illinois Toxic air contaminant BNA 2001 

 Kansas HAP BNA 2001 

Kentucky HAP BNA 2001 

Maryland Toxic air pollutant BNA 2001 

 Selenium sulfide 

Minnesota HAP threshold—de minimis level BNA 2001 

 Selenium compounds 0.1 ton/year 

 Selenium sulfide 0.1 ton/year 

Nebraska HAP—effective date 12/15/98 BNA 2001 

New Hampshire Regulated toxic air pollutant BNA 2001 

New Mexico Toxic air pollutant BNA 2001 

OEL 0.2 mg/m3
 

 Emissions 0.0133 mg/m3
 

New York HAP—selenium compounds BNA 2001 

allowable concentration 

 Selenium compounds 1 μg/m3
 

Rhode Island HAP BNA 2001 

South Carolina Toxic air emissions—maximum BNA 2001 

Vermont Hazardous ambient air standards BNA 2001 

 Annual average 4.80 μg/m3
 

 Action level 0.40 pounds/8-hours 

 Washington HAP—threshold levels BNA 2001 

Selenium and compounds 0.5 tons/year 

 Selenium hexafluoride 0.5 tons/year 

 Selenium sulfides 0.5 tons/year 

b. Water 

Alabama Aquatic life criteria BNA 2001 

 Freshwater
 

Acute 20 μg/L 

Chronic 5.0 μg/L 

Marine 

Acute 300 μg/L 

Chronic 71 μg/L 

MCL 0.05 mg/L BNA 2001 

Primary drinking water standard 0.01 mg/L BNA 2001 

Alaska Groundwater cleanup level 0.05 mg/L BNA 2001 

MCL 0.05 mg/L BNA 2001 

Arizona Aquifer water quality standards 0.05 mg/L BNA 2001 

Drinking water guideline 45 μg/L HSDB 2001 

MCL 0.05 mg/L BNA 2001 

Water quality standards EPA 2001r 

 Conversion factore

 for 40CFR131.38 

 saltwater—acute criteria 0.998 

 Conversion factore

 for 

 saltwater—chronic criteria 0.998 
SELENIUM	 308
 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Selenium 

Agency Description Information References 

STATE (cont.) 

Colorado Groundwater protection—MCL 0.01 mg/L BNA 2001 

MCL 0.05 mg/L BNA 2001 

Primary drinking water standard 0.01 mg/L BNA 2001 

Connecticut MCL 0.05 mg/L BNA 2001 

Delaware Groundwater protection—MCL 0.01 mg/L BNA 2001 

Primary drinking water standard 0.01 mg/L BNA 2001 

Florida MCL 0.05 mg/L BNA 2001 

Georgia MCL 0.05 mg/L BNA 2001 

Hawaii MCL 0.05 mg/L BNA 2001 

Water quality criteria applicable to BNA 2001 

all waters 

 Freshwater 

Acute 20 μg/L 

Chronic 5.0 μg/L 

Saltwater 

Acute 300 μg/L 

Chronic 71 μg/L 

Illinois Concentration shall not be exceeded 1.0 mg/L BNA 2001 

in water 

MCL 0.05 mg/L 

Groundwater quality standard 0.01 mg/L BNA 2001 

MCL 0.05 mg/L BNA 2001 

Indiana MCLG 0.05 mg/L BNA 2001 

Iowa MCL 0.05 mg/L BNA 2001 

Kansas Surface water quality standard BNA 2001 

 Aquatic life 

Acute 20 μg/L 

Chronic 5.0 μg/L 

Agriculture 

Livestock 50 μg/L 

Irrigation 20 μg/L 

Public health food 

Procurement 6,800 μg/L 

Domestic water supply 50 μg/L 

Kentucky Domestic water supply use— 0.05 mg/L BNA 2001 

maximum allowable instream 

concentration 

MCL 0.05 mg/L BNA 2001 

level 

Acute 

 Chronic 20 μg/L 

 Maximum groundwater contaminant 0.01 mg/L BNA 2001 

Kentucky Primary drinking water standard 0.01 mg/L BNA 2001 

Warm water aquatic habitat criteria BNA 2001 

5.0 μg/L 
SELENIUM 309 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Selenium 

Agency Description Information References 

STATE (cont.) 

Louisiana Groundwater protection—MCL 0.01 mg/L BNA 2001 

Maine Drinking water guideline 10 μg/L HSDB 2001 

Maryland Criteria for toxic substances in 

surface waters

BNA 2001 

 Freshwater 

Acute 

Chronic 

Saltwater 

20 μg/L 

5.0 μg/L 

Acute 

Chronic 

 Drinking water 

300 μg/L 

71 μg/L 

50 μg/L 

MCL 0.05 mg/L BNA 2001 

Primary drinking water standard 0.01 mg/L BNA 2001 

Massachusetts Environmental toxicity values

 Freshwater 

Acute 

Chronic 

20 μg/L 

5.0 μg/L 

BNA 2001 

Marine 

Acute 

Chronic 

300 μg/L 

71 μg/L 

Groundwater protection—MCL 0.01 mg/L BNA 2001 

MCL 0.05 mg/L BNA 2001 

 Michigan MCL 

Effective date 

0.05 mg/L 

07/30/92 

BNA 2001 

Minnesota Drinking water guideline 30 μg/L HSDB 2001 

Mississippi Groundwater standard 50 ppb BNA 2001 

Water quality criteria— 

concentration shall not exceed 

0.01 mg/L BNA 2001 

Montana MCL 0.05 mg/L BNA 2001 

North Carolina Fresh surface water quality standard 

for Class C waters 

5.0 ug/L BNA 2001 

Groundwater quality standard 0.05 mg/L BNA 2001 

 Nebraska Aquatic life 

Acute 

 Chronic 

20 μg/L 

5.0 μg/L 

BNA 2001 

Water supply 0.05 mg/L BNA 2001 

MCL 0.05 mg/L BNA 2001 

New Hampshire Groundwater quality standard 0.05 mg/L 

MCLG 

MCL 

0.05 mg/L 

0.05 mg/L 

BNA 2001 
SELENIUM 310 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Selenium 

Agency Description Information References 

STATE (cont.) 

New Hampshire Water quality criteria BNA 2001 

Protection of aquatic life 

 Fresh 

acute 5.0 μg/L 

chronic 290μg/L 

Marine 

acute 71 μg/L 

chronic 170 μg/L 

Protection of human health 

Water and fish ingestion 11,000 μg/L 

New Mexico MCL 0.05 mg/L BNA 2001 

 Nevada Domestic water supply BNA 2001 

 Dissolved selenium 0.05 mg/L 

New York MCL 0.05 mg/L BNA 2001 

North Dakota MCL 0.05 mg/L BNA 2001 

Ohio Groundwater concentration limit 0.01 mg/L BNA 2001 

Oklahoma Public and private water supplies 0.01 mg/L BNA 2001 

Fish and wildlife propagation BNA 2001 

Acute 20 μg/L 

 Chronic 5.0 μg/L 

Rhode Island Groundwater quality standard 0.05 mg/L BNA 2001 

Preventive action limit 0.025 mg/L 

South Carolina MCL 0.05 mgL BNA 2001 

South Dakota Groundwater maximum allowable 0.05 mg/L BNA 2001 

concentration 

Aquatic life value BNA 2001 

Acute 20 μg/L 

 Chronic 5.0 μg/L 

Tennessee Groundwater criteria concentration 0.05 mg/L BNA 2001 

MCL 0.05 mg/L BNA 2001 

Texas MCL 0.05 mg/L BNA 2001 

Utah MCL 0.05 mg/L BNA 2001 

 Water quality BNA 2001 

 Domestic 0.01 mg/L 

Agriculture 0.05 mg/L 

Vermont Groundwater quality standards BNA 2001 

 Enforcement standard 50 μg/L 

Preventive action level 25 μg/L 

MCLG 0.05 mg/L BNA 2001 

MCL 0.05 mg/L 
SELENIUM 311 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Selenium 

Agency Description Information References 

STATE (cont.) 

Vermont Water quality criteria for protection 

of aquatic organisms 

Maximum allowable 

BNA 2001 

 concentration 

Acute 

Average allowable 

 concentration 

20 μg/L 

Chronic 5.0 μg/L 

Virginia Groundwater protection levels 

 Protection level 

 Monitoring level 

10 μg/L 

5.0 μg/L 

BNA 2001 

MCL 0.01 mg/L BNA 2001 

Surface water criteria BNA 2001 

 Freshwater 

Acute 

Chronic 

Saltwater 

20 μg/L 

5.0 μg/L 

Acute 

Chronic 

 Human health 

300 μg/L 

71 μg/L 

Public water supplies 

All other surface waters 

170 μg/L 

11,000 μg/L 

Washington MCL 0.05 mg/L BNA 2001 

Wisconsin Groundwater quality standards

 Enforcement standard 

Preventive action limit 

50 μg/L 

10 μg/L 

BNA 2001 

MCL 0.05 mg/L BNA 2001 

Wyoming Water quality 

 Aquatic life 

Acute 

Chronic 

 Human health 

20 μg/L 

5.0 μg/L 

10 μg/L 

BNA 2001 

c. Food 

New York Bottled water sampling 

requirements—MCL 

0.01 mg/L BNA 2001 

d. Other 

Alabama Identification and listing of 

hazardous waste 

 BNA 2001 

Arizona Soil remediation levels BNA 2001 

 Residential 

 Non-residential 

380 mg/kg 

8,500 mg/kg 

California Hazardous waste injection 

restrictions—waste specific 

prohibitions 

Selenium and/or compounds 100 mg/L 

EPA 2001s 

40CFR148.12 

(b)(2) 
SELENIUM 312 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Selenium 

Agency Description Information References 

STATE (cont.) 

California Known to cause cancer or BNA 2001 

reproductive toxicity—initial 

appearance of chemical on list 

 Selenium sulfide 10/01/89 

Total threshold limit concentration 10,000 mg/kg BNA 2001 

Delaware Regulated toxic substance— 

sufficient quantity 

 Selenium hexafluoride 900 pounds/hour 

BNA 2001 

Florida Toxic substance in the workplace 

 Hydrogen selenium 

Selenium 

 BNA 2001 

 Selenium hexafluoride 

 Selenium oxychloride 

 Selenium sulfide 

Hawaii Restricted use pesticides 

 Selenium compounds All concentrations 

BNA 2001 

Kentucky Threshold planning quantity 

 Hydrogen selenide 

 Selenious acid 

 Selenium oxychloride 

10 pounds 

1,000/10,000 pounds 

500 pounds 

BNA 2001 

Massachusetts Oil and hazardous material BNA 2001 

 Selenious acid 

Selenium and compounds 

 Selenium dioxide 

 Selenium disulfide 

 Selenium oxide 

 Selenium oxychloride 

 Selenium sulfide 

 Selenourea 

 Minnesota RfD 

Health risk limit 

0.005 mg/kg/day 

30 μg/L 

BNA 2001 

New Hampshire Restricted use pesticide All concentrations BNA 2001 

New Jersey Extraordinary hazardous 

substance—threshold quantity 

 Selenium hexafluoride 700 pounds 

BNA 2001 
SELENIUM 313 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Selenium 

Agency Description Information References 

STATE (cont.) 

Oregon Toxic substance—de minimis 1.0 percent BNA 2001 

concentration 

Vermont Restricted use pesticide All concentrations BNA 2001 

Selenium and compounds 

a

Group 3: not classifiable as to its carcinogenicity to humans

b

Group D: not classifiable as to its carcinogenicity to humans 

c

Group B2: probable human carcinogen 

d

Monthly average concentrations 

e

Conversion factors are based on a hardness of 100 mg/L as calcium carbonate 

ACGIH = American Conference of Governmental Industrial Hygienists; BNA = Bureau of National Affairs; 

CFR = Code of Federal Regulations; DWEL = drinking water equivalent level; EPA = Environmental Protection 

Agency; FDA = Food and Drug Administration; HAP = hazardous air pollutant; IARC = International Agency for 

Research on Cancer; IDLH = immediately dangerous to life and health; IRIS = Integrated Risk Information System; 

MCL = maximum contaminant level; MCLG = maximum contaminant level goal; NIOSH = National Institute for 

Occupational Safety and Health; OEL = occupational exposure limit; OSHA = Occupational Safety and Health 

Administration; PEL = permissible exposure limit; PQL = practical quantitation limit; RDA = recommended daily 

allowance; REL = recommended exposure limit; RfD = reference dose; TLV = threshold limit value; TWA = timeweighted average; WHO = World Health Organization 

_______________________ 

SELENIUM 315 

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SELENIUM 413 

10. GLOSSARY 

Absorption—The taking up of liquids by solids, or of gases by solids or liquids. 

Acute Exposure—Exposure to a chemical for a duration of 14 days or less, as specified in the 

Toxicological Profiles. 

Adsorption—The adhesion in an extremely thin layer of molecules (as of gases, solutes, or liquids) to the 

surfaces of solid bodies or liquids with which they are in contact. 

Adsorption Coefficient (Koc)—The ratio of the amount of a chemical adsorbed per unit weight of 

organic carbon in the soil or sediment to the concentration of the chemical in solution at equilibrium. 

Adsorption Ratio (Kd)—The amount of a chemical adsorbed by a sediment or soil (i.e., the solid phase) 

divided by the amount of chemical in the solution phase, which is in equilibrium with the solid phase, at a 

fixed solid/solution ratio. It is generally expressed in micrograms of chemical sorbed per gram of soil or 

sediment. 

Benchmark Dose (BMD)—Usually defined as the lower confidence limit on the dose that produces a 

specified magnitude of changes in a specified adverse response. For example, a BMD10 would be the 

dose at the 95% lower confidence limit on a 10% response, and the benchmark response (BMR) would be 

10%. The BMD is determined by modeling the dose response curve in the region of the dose response 

relationship where biologically observable data are feasible. 

Benchmark Dose Model—A statistical dose-response model applied to either experimental toxicological 

or epidemiological data to calculate a BMD. 

Bioconcentration Factor (BCF)—The quotient of the concentration of a chemical in aquatic organisms 

at a specific time or during a discrete time period of exposure divided by the concentration in the 

surrounding water at the same time or during the same period. 

Biomarkers—Broadly defined as indicators signaling events in biologic systems or samples. They have 

been classified as markers of exposure, markers of effect, and markers of susceptibility. 

Cancer Effect Level (CEL)—The lowest dose of chemical in a study, or group of studies, that produces 

significant increases in the incidence of cancer (or tumors) between the exposed population and its 

appropriate control. 

Carcinogen—A chemical capable of inducing cancer. 

Case-Control Study—A type of epidemiological study which examines the relationship between a 

particular outcome (disease or condition) and a variety of potential causative agents (such as toxic 

chemicals). In a case-controlled study, a group of people with a specified and well-defined outcome is 

identified and compared to a similar group of people without outcome. 

Case Report—Describes a single individual with a particular disease or exposure. These may suggest 

some potential topics for scientific research but are not actual research studies. 

Case Series—Describes the experience of a small number of individuals with the same disease or 

exposure. These may suggest potential topics for scientific research but are not actual research studies. 
SELENIUM 414 

10. GLOSSARY 

Ceiling Value—A concentration of a substance that should not be exceeded, even instantaneously. 

Chronic Exposure—Exposure to a chemical for 365 days or more, as specified in the Toxicological 

Profiles. 

Cohort Study—A type of epidemiological study of a specific group or groups of people who have had a 

common insult (e.g., exposure to an agent suspected of causing disease or a common disease) and are 

followed forward from exposure to outcome. At least one exposed group is compared to one unexposed 

group. 

Cross-sectional Study—A type of epidemiological study of a group or groups which examines the 

relationship between exposure and outcome to a chemical or to chemicals at one point in time. 

Data Needs—Substance-specific informational needs that if met would reduce the uncertainties of human 

health assessment. 

Developmental Toxicity—The occurrence of adverse effects on the developing organism that may result 

from exposure to a chemical prior to conception (either parent), during prenatal development, or 

postnatally to the time of sexual maturation. Adverse developmental effects may be detected at any point 

in the life span of the organism. 

Dose-Response Relationship—The quantitative relationship between the amount of exposure to a 

toxicant and the incidence of the adverse effects. 

Embryotoxicity and Fetotoxicity—Any toxic effect on the conceptus as a result of prenatal exposure to 

a chemical; the distinguishing feature between the two terms is the stage of development during which the 

insult occurs. The terms, as used here, include malformations and variations, altered growth, and in utero 

death. 

Environmental Protection Agency (EPA) Health Advisory—An estimate of acceptable drinking water 

levels for a chemical substance based on health effects information. A health advisory is not a legally 

enforceable federal standard, but serves as technical guidance to assist federal, state, and local officials. 

Epidemiology—Refers to the investigation of factors that determine the frequency and distribution of 

disease or other health-related conditions within a defined human population during a specified period. 

Genotoxicity—A specific adverse effect on the genome of living cells that, upon the duplication of 

affected cells, can be expressed as a mutagenic, clastogenic or carcinogenic event because of specific 

alteration of the molecular structure of the genome. 

Half-life—A measure of rate for the time required to eliminate one half of a quantity of a chemical from 

the body or environmental media. 

Immediately Dangerous to Life or Health (IDLH)—The maximum environmental concentration of a 

contaminant from which one could escape within 30 minutes without any escape-impairing symptoms or 

irreversible health effects. 

Incidence—The ratio of individuals in a population who develop a specified condition to the total 

number of individuals in that population who could have developed that condition in a specified time 

period. 
SELENIUM 415 

10. GLOSSARY 

Intermediate Exposure—Exposure to a chemical for a duration of 15–364 days, as specified in the 

Toxicological Profiles. 

Immunologic Toxicity—The occurrence of adverse effects on the immune system that may result from 

exposure to environmental agents such as chemicals. 

Immunological Effects—Functional changes in the immune response. 

In Vitro—Isolated from the living organism and artificially maintained, as in a test tube. 

In Vivo—Occurring within the living organism. 

Lethal Concentration(LO) (LCLO)—The lowest concentration of a chemical in air which has been 

reported to have caused death in humans or animals. 

Lethal Concentration(50) (LC50)—A calculated concentration of a chemical in air to which exposure for 

a specific length of time is expected to cause death in 50% of a defined experimental animal population. 

Lethal Dose(LO) (LDLO)—The lowest dose of a chemical introduced by a route other than inhalation that 

has been reported to have caused death in humans or animals. 

Lethal Dose(50) (LD50)—The dose of a chemical which has been calculated to cause death in 50% of a 

defined experimental animal population. 

Lethal Time(50) (LT50)—A calculated period of time within which a specific concentration of a chemical 

is expected to cause death in 50% of a defined experimental animal population. 

Lowest-Observed-Adverse-Effect Level (LOAEL)—The lowest exposure level of chemical in a study, 

or group of studies, that produces statistically or biologically significant increases in frequency or severity 

of adverse effects between the exposed population and its appropriate control. 

Lymphoreticular Effects—Represent morphological effects involving lymphatic tissues such as the 

lymph nodes, spleen, and thymus. 

Malformations—Permanent structural changes that may adversely affect survival, development, or 

function. 

Minimal Risk Level (MRL)—An estimate of daily human exposure to a hazardous substance that is 

likely to be without an appreciable risk of adverse noncancer health effects over a specified route and 

duration of exposure. 

Modifying Factor (MF)—A value (greater than zero) that is applied to the derivation of a minimal risk 

level (MRL) to reflect additional concerns about the database that are not covered by the uncertainty 

factors. The default value for a MF is 1. 

Morbidity—State of being diseased; morbidity rate is the incidence or prevalence of disease in a specific 

population. 

Mortality—Death; mortality rate is a measure of the number of deaths in a population during a specified 

interval of time. 
SELENIUM 416 

10. GLOSSARY 

Mutagen—A substance that causes mutations. A mutation is a change in the DNA sequence of a cell’s 

DNA. Mutations can lead to birth defects, miscarriages, or cancer. 

Necropsy—The gross examination of the organs and tissues of a dead body to determine the cause of 

death or pathological conditions. 

Neurotoxicity—The occurrence of adverse effects on the nervous system following exposure to a 

chemical. 

No-Observed-Adverse-Effect Level (NOAEL)—The dose of a chemical at which there were no 

statistically or biologically significant increases in frequency or severity of adverse effects seen between 

the exposed population and its appropriate control. Effects may be produced at this dose, but they are not 

considered to be adverse. 

Octanol-Water Partition Coefficient (Kow)—The equilibrium ratio of the concentrations of a chemical 

in n-octanol and water, in dilute solution. 

Odds Ratio (OR)—A means of measuring the association between an exposure (such as toxic substances 

and a disease or condition) which represents the best estimate of relative risk (risk as a ratio of the 

incidence among subjects exposed to a particular risk factor divided by the incidence among subjects who 

were not exposed to the risk factor). An odds ratio of greater than 1 is considered to indicate greater risk 

of disease in the exposed group compared to the unexposed. 

Organophosphate or Organophosphorus Compound—A phosphorus containing organic compound 

and especially a pesticide that acts by inhibiting cholinesterase. 

Permissible Exposure Limit (PEL)—An Occupational Safety and Health Administration (OSHA) 

allowable exposure level in workplace air averaged over an 8-hour shift of a 40-hour workweek. 

Pesticide—General classification of chemicals specifically developed and produced for use in the control 

of agricultural and public health pests. 

Pharmacokinetics—The science of quantitatively predicting the fate (disposition) of an exogenous 

substance in an organism. Utilizing computational techniques, it provides the means of studying the 

absorption, distribution, metabolism and excretion of chemicals by the body. 

Pharmacokinetic Model—A set of equations that can be used to describe the time course of a parent 

chemical or metabolite in an animal system. There are two types of pharmacokinetic models: data-based 

and physiologically-based. A data-based model divides the animal system into a series of compartments 

which, in general, do not represent real, identifiable anatomic regions of the body whereby the 

physiologically-based model compartments represent real anatomic regions of the body. 

Physiologically Based Pharmacodynamic (PBPD) Model—A type of physiologically-based doseresponse model which quantitatively describes the relationship between target tissue dose and toxic end 

points. These models advance the importance of physiologically based models in that they clearly 

describe the biological effect (response) produced by the system following exposure to an exogenous 

substance. 
SELENIUM 417 

10. GLOSSARY 

Physiologically Based Pharmacokinetic (PBPK) Model—Comprised of a series of compartments 

representing organs or tissue groups with realistic weights and blood flows. These models require a 

variety of physiological information: tissue volumes, blood flow rates to tissues, cardiac output, alveolar 

ventilation rates and, possibly membrane permeabilities. The models also utilize biochemical information 

such as air/blood partition coefficients, and metabolic parameters. PBPK models are also called 

biologically based tissue dosimetry models. 

Prevalence—The number of cases of a disease or condition in a population at one point in time. 

Prospective Study—A type of cohort study in which the pertinent observations are made on events 

occurring after the start of the study. A group is followed over time. 

q1*—The upper-bound estimate of the low-dose slope of the dose-response curve as determined by the 

multistage procedure. The q1* can be used to calculate an estimate of carcinogenic potency, the 

incremental excess cancer risk per unit of exposure (usually μg/L for water, mg/kg/day for food, and 

μg/m3

 for air). 

Recommended Exposure Limit (REL)—A National Institute for Occupational Safety and Health 

(NIOSH) time-weighted average (TWA) concentrations for up to a 10-hour workday during a 40-hour 

workweek. 

Reference Concentration (RfC)—An estimate (with uncertainty spanning perhaps an order of 

magnitude) of a continuous inhalation exposure to the human population (including sensitive subgroups) 

that is likely to be without an appreciable risk of deleterious noncancer health effects during a lifetime. 

The inhalation reference concentration is for continuous inhalation exposures and is appropriately 

expressed in units of mg/m3 or ppm. 

Reference Dose (RfD)—An estimate (with uncertainty spanning perhaps an order of magnitude) of the 

daily exposure of the human population to a potential hazard that is likely to be without risk of deleterious 

effects during a lifetime. The RfD is operationally derived from the no-observed-adverse-effect level 

(NOAEL-from animal and human studies) by a consistent application of uncertainty factors that reflect 

various types of data used to estimate RfDs and an additional modifying factor, which is based on a 

professional judgment of the entire database on the chemical. The RfDs are not applicable to 

nonthreshold effects such as cancer. 

Reportable Quantity (RQ)—The quantity of a hazardous substance that is considered reportable under 

the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA). Reportable 

quantities are (1) 1 pound or greater or (2) for selected substances, an amount established by regulation 

either under CERCLA or under Section 311 of the Clean Water Act. Quantities are measured over a 24­

hour period. 

Reproductive Toxicity—The occurrence of adverse effects on the reproductive system that may result 

from exposure to a chemical. The toxicity may be directed to the reproductive organs and/or the related 

endocrine system. The manifestation of such toxicity may be noted as alterations in sexual behavior, 

fertility, pregnancy outcomes, or modifications in other functions that are dependent on the integrity of 

this system. 

Retrospective Study—A type of cohort study based on a group of persons known to have been exposed 

at some time in the past. Data are collected from routinely recorded events, up to the time the study is 

undertaken. Retrospective studies are limited to causal factors that can be ascertained from existing 

records and/or examining survivors of the cohort. 
SELENIUM 418 

10. GLOSSARY 

Risk—The possibility or chance that some adverse effect will result from a given exposure to a chemical. 

Risk Factor—An aspect of personal behavior or lifestyle, an environmental exposure, or an inborn or 

inherited characteristic, that is associated with an increased occurrence of disease or other health-related 

event or condition. 

Risk Ratio—The ratio of the risk among persons with specific risk factors compared to the risk among 

persons without risk factors. A risk ratio greater than 1 indicates greater risk of disease in the exposed 

group compared to the unexposed. 

Short-Term Exposure Limit (STEL)—The American Conference of Governmental Industrial 

Hygienists (ACGIH) maximum concentration to which workers can be exposed for up to 15 minutes 

continually. No more than four excursions are allowed per day, and there must be at least 60 minutes 

between exposure periods. The daily Threshold Limit Value - Time Weighted Average (TLV-TWA) may 

not be exceeded. 

Standardized Mortality Ratio (SMR)—A ratio of the observed number of deaths and the expected 

number of deaths in a specific standard population. 

Target Organ Toxicity—This term covers a broad range of adverse effects on target organs or 

physiological systems (e.g., renal, cardiovascular) extending from those arising through a single limited 

exposure to those assumed over a lifetime of exposure to a chemical. 

Teratogen—A chemical that causes structural defects that affect the development of an organism. 

Threshold Limit Value (TLV)—An American Conference of Governmental Industrial Hygienists 

(ACGIH) concentration of a substance to which most workers can be exposed without adverse effect. 

The TLV may be expressed as a Time Weighted Average (TWA), as a Short-Term Exposure Limit 

(STEL), or as a ceiling limit (CL). 

Time-Weighted Average (TWA)—An allowable exposure concentration averaged over a normal 8-hour 

workday or 40-hour workweek. 

Toxic Dose(50) (TD50)—A calculated dose of a chemical, introduced by a route other than inhalation, 

which is expected to cause a specific toxic effect in 50% of a defined experimental animal population. 

Toxicokinetic—The study of the absorption, distribution and elimination of toxic compounds in the 

living organism. 

Uncertainty Factor (UF)—A factor used in operationally deriving the Minimal Risk Level (MRL) or 

Reference Dose (RfD) or Reference Concentration (RfC) from experimental data. UFs are intended to 

account for (1) the variation in sensitivity among the members of the human population, (2) the 

uncertainty in extrapolating animal data to the case of human, (3) the uncertainty in extrapolating from 

data obtained in a study that is of less than lifetime exposure, and (4) the uncertainty in using lowestobserved-adverse-effect level (LOAEL) data rather than no-observed-adverse-effect level (NOAEL) data. 

A default for each individual UF is 10; if complete certainty in data exists, a value of one can be used; 

however a reduced UF of three may be used on a case-by-case basis, three being the approximate 

logarithmic average of 10 and 1. 

Xenobiotic—Any chemical that is foreign to the biological system. 
SELENIUM A-1 

APPENDIX A. ATSDR MINIMAL RISK LEVELS AND WORKSHEETS 

The Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) [42 U.S.C. 

9601 et seq.], as amended by the Superfund Amendments and Reauthorization Act (SARA) [Pub. L. 99– 

499], requires that the Agency for Toxic Substances and Disease Registry (ATSDR) develop jointly with 

the U.S. Environmental Protection Agency (EPA), in order of priority, a list of hazardous substances most 

commonly found at facilities on the CERCLA National Priorities List (NPL); prepare toxicological 

profiles for each substance included on the priority list of hazardous substances; and assure the initiation 

of a research program to fill identified data needs associated with the substances. 

The toxicological profiles include an examination, summary, and interpretation of available toxicological 

information and epidemiologic evaluations of a hazardous substance. During the development of 

toxicological profiles, Minimal Risk Levels (MRLs) are derived when reliable and sufficient data exist to 

identify the target organ(s) of effect or the most sensitive health effect(s) for a specific duration for a 

given route of exposure. An MRL is an estimate of the daily human exposure to a hazardous substance 

that is likely to be without appreciable risk of adverse noncancer health effects over a specified duration 

of exposure. MRLs are based on noncancer health effects only and are not based on a consideration of 

cancer effects. These substance-specific estimates, which are intended to serve as screening levels, are 

used by ATSDR health assessors to identify contaminants and potential health effects that may be of 

concern at hazardous waste sites. It is important to note that MRLs are not intended to define clean-up or 

action levels. 

MRLs are derived for hazardous substances using the no-observed-adverse-effect level/uncertainty factor 

approach. They are below levels that might cause adverse health effects in the people most sensitive to 

such chemical-induced effects. MRLs are derived for acute (1–14 days), intermediate (15–364 days), and 

chronic (365 days and longer) durations and for the oral and inhalation routes of exposure. Currently, 

MRLs for the dermal route of exposure are not derived because ATSDR has not yet identified a method 

suitable for this route of exposure. MRLs are generally based on the most sensitive chemical-induced end 

point considered to be of relevance to humans. Serious health effects (such as irreparable damage to the 

liver or kidneys, or birth defects) are not used as a basis for establishing MRLs. Exposure to a level 

above the MRL does not mean that adverse health effects will occur. 
SELENIUM A-2 

APPENDIX A 

MRLs are intended only to serve as a screening tool to help public health professionals decide where to 

look more closely. They may also be viewed as a mechanism to identify those hazardous waste sites that 

are not expected to cause adverse health effects. Most MRLs contain a degree of uncertainty because of 

the lack of precise toxicological information on the people who might be most sensitive (e.g., infants, 

elderly, nutritionally or immunologically compromised) to the effects of hazardous substances. ATSDR 

uses a conservative (i.e., protective) approach to address this uncertainty consistent with the public health 

principle of prevention. Although human data are preferred, MRLs often must be based on animal studies 

because relevant human studies are lacking. In the absence of evidence to the contrary, ATSDR assumes 

that humans are more sensitive to the effects of hazardous substance than animals and that certain persons 

may be particularly sensitive. Thus, the resulting MRL may be as much as a hundredfold below levels 

that have been shown to be nontoxic in laboratory animals. 

Proposed MRLs undergo a rigorous review process: Health Effects/MRL Workgroup reviews within the 

Division of Toxicology, expert panel peer reviews, and agency wide MRL Workgroup reviews, with 

participation from other federal agencies and comments from the public. They are subject to change as 

new information becomes available concomitant with updating the toxicological profiles. Thus, MRLs in 

the most recent toxicological profiles supersede previously published levels. For additional information 

regarding MRLs, please contact the Division of Toxicology, Agency for Toxic Substances and Disease 

Registry, 1600 Clifton Road NE, Mailstop E-29, Atlanta, Georgia 30333. 
SELENIUM A-3 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical Name: Selenium 

CAS Number: 7782-49-2 (elemental) 

Date: June 5, 2003 

Profile Status: Post Public Comments, Draft 3 

Route: [ ] Inhalation [X] Oral 

Duration: [ ] Acute [ ] Intermediate [X] Chronic 

Graph Key: 101 

Species: Human 

Minimal Risk Level: 0.005 [X] mg/kg/day [ ] ppm 

Reference: Yang G, Zhou R. 1994. Further observations on the human maximum safe dietary selenium 

intake in a seleniferous area of China. J Trace Elem Electrolytes Health Dis 8:159-165. 

Experimental design: This study was an examination of a group of five individuals who were recovering 

from selenosis, and who had been drawn from a larger population studied by the same authors (Yang et 

al. 1989a, 1989b). Yang et al. (1989a, 1989b) examined a population in an area of China where selenosis 

occurred. Data were collected on selenium levels in the diet, blood, nails, hair, urine, and milk of 

residents, and the incidence of clinical symptoms of selenosis (morphological changes in fingernails) was 

compared with dietary intake of selenium and selenium levels in blood. Selenium levels in blood 

corresponded to the dietary intake of selenium, and symptoms of selenosis occurred at or above a 

selenium intake level of 910 μg/day (0.016 mg/kg/day) (Yang et al 1989a). In 1992, Yang and Zhou 

(1994) reexamined five individuals from the high selenium site who had been suffering from symptoms 

of selenosis (loss of fingernails and hair), but were recovering (nails were regrowing). Since their earlier 

report, the living conditions of the population had improved; they had been cautioned against consuming 

high selenium foods and parts of their locally produced corn had been replaced with rice or cereals. Yang 

and Zhou (1994) found that the mean concentration of selenium in the blood of these selenosis patients 

had fallen from 1,346 μg/L (measured in 1986) to 968 μg/L (measured in 1992). Using a regression 

equation derived from the data in their earlier report (Yang et al. 1989b) and average body weights of 

55 kg, Yang and Zhou (1994) calculated that the mean dietary intake of selenium associated with 

selenosis in these individuals was 1,270 μg/day (LOAEL of 0.023 mg/kg/day), while a mean intake of 

819 μg selenium/day (NOAEL of 0.015 mg/kg/day) was associated with recovery. 

Effects noted in study and corresponding doses: A NOAEL of 0.015 mg/kg/day for nail disease based on 

recovery from symptoms of selenosis, and a LOAEL of 0.023 mg/kg/day based on nail damage were 

calculated from selenium concentrations in blood using average body weights of 55 kg and the regression 

equation: Yblood-Se (mg/L) = 8230 x 10-4 Xse-intake (μg) + 0.176 derived in Yang et al. (1989b). 

Dose and end point used for MRL derivation: 0.015 mg/kg/day; nail disease (selenosis) 

[X] NOAEL [ ] LOAEL 

Uncertainty Factors used in MRL derivation: 

[ ] 10 for use of a LOAEL 

[ ] 10 for extrapolation from animals to humans 

[X] 3 for human variability 
SELENIUM A-4 

APPENDIX A 

A factor of 3 was considered appropriate because the individuals in this report were sensitive individuals 

drawn from the larger population in the Yang et al. (1989a, 1989b) studies and because of the supporting 

studies described below. 

Was a conversion used from ppm in food or water to a mg/body weight dose? No. 

If so, explain: 

If an inhalation study in animals, list the conversion factors used in determining human equivalent dose: 

NA 

Other additional studies or pertinent information which lend support to this MRL: 

Yang et al. (1989a, 1989b) examined a population of 349 individuals in an area of China where selenosis 

occurred. They collected data on selenium levels in the diet, blood, nails, hair, urine, and milk of 

residents at three sites with low, medium, and high selenium, and compared the incidence of clinical 

symptoms of selenosis (morphological changes in finger nails) with dietary intake of selenium and 

selenium levels in blood. They found that selenium levels in blood corresponded to the dietary intake of 

selenium, and that symptoms of selenosis were found at or above a selenium intake level of 910 μg/day 

(0.016 mg/kg/day) (Yang et al 1989a). The population included adult men and women, teenagers, 

children, and infants. High selenium levels were found in individuals of all ages, but symptoms of 

selenosis were generally confined to adults (97% of cases) and were never observed in children younger 

than 12 years of age (Yang et al. 1989b). The manifestation of symptoms of selenosis was not solely 

dependent on selenium intake, but was subject to individual variability, as individuals who exhibited 

selenosis did not necessarily have the highest blood selenium levels. 

Longnecker et al. (1991) examined two groups of adults (142 individuals) in areas of Wyoming and South 

Dakota with elevated selenium intake. The average daily intake of selenium in this population was 

239 μg/day (0.003 mg/kg/day) and some individuals consumed as much as 724 μg/day (0.01 mg/kg/day). 

The highest blood concentration of selenium noted in this population was 0.67 mg/kg, a concentration 

lower than the 1.05 mg/L concentration associated with effects in China. No symptoms of selenosis or 

any other significant health effects associated with selenium exposure were reported for individuals in this 

study. This study suggests that the estimates of dietary intake of selenium produced by the regression 

equation in Yang et al. (1989b) may be conservative. Longnecker et al. (1991) reported doses of 

68–724 μg/day associated with blood concentrations of 0.18–0.67 mg/kg. If the doses from the 

Longnecker et al. (1991) study are placed in the regression equation from Yang et al. (1989b), blood 

concentrations of 0.14 and 0.88 mg/L are calculated. If it is assumed that a liter of blood weighs 

approximately 1 kg, then this regression equation overpredicts blood levels of selenium at the higher 

doses in the population from North Dakota. This provides support for additional exposure (e.g., 

inhalation exposure) in the Chinese population that was not accounted for in the regression equation. 

Selenium is a component of all three members of the deiodinase enzyme family, the enzymes responsible 

for deiodination of the thyroid hormones (St. Germain and Galton 1997). Two human studies were 

located that describe significant decreases in triiodothyronine levels in response to elevated selenium; 

however, the hormone levels observed in these studies were subclinical within the normal human range 

and the biological significance of the effect is not clear. In the first study, Brätter and Negretti De Brätter 

(1996) examined a Venezuelan population with high selenium intake. Serum, erythrocyte, toenail, and 

breast milk selenium concentrations were determined for 65 women living in three seleniferous regions of 

Venezuela. Selenium dietary intakes were determined from the selenium concentration of breast milk by 

regression (Bratter et al. 1991), and free thyroxine (T4), free triiodothyronine (T3), and human thyroid 

stimulating hormone (TSH) levels were measured. Selenium intake ranged from 170 to 980 μg/day. 

There was a significant inverse correlation between free T3 and selenium levels in serum (Spearman R 
SELENIUM A-5 

APPENDIX A 

test), but free T3, free T4, and TSH levels were found to be within normal ranges. No symptoms of 

selenosis were found in the women included in this study. 

In the second human study, serum hormone, semen, immunological, and hematological status was 

evaluated in a 120-day double blind study of healthy men (20–45 years old) who consumed a controlled 

diet of foods naturally low or high in selenium (Hawkes and Turek 2001; Hawkes et al. 2001). Eleven 

subjects were fed a diet that provided 47 μg Se/day (0.0006 mg/kg/day) for the first 21 days of the study. 

For the following 99 days, six of the subjects were fed a diet providing 13 μg Se/day (0.0002 mg/kg/day), 

and five of the remaining subjects were fed a diet providing 297 μg/day (0.004 mg/kg/day). 

Comprehensive evaluations were performed at weeks 3 (baseline), 17 (ending value), and several interim 

time points on end points that included selenium levels (in blood plasma, erythrocytes, seminal plasma, 

and sperm); thyroid hormone levels (serum T3 and TSH); reproductive hormone levels (serum 

testosterone, follicle-stimulating hormone, luteinizing hormone, prolactin, estradiol, and progesterone); 

semen quality (sperm concentration, semen volume, sperm total number, fraction motile sperm, percent 

progressive sperm, mean forward velocity, and various sperm morphology parameters); immunological 

indices (complete blood counts, lymphocyte phenotypes, serum immunoglobulins (IgA, IgG, IgM); 

complement fractions; peripheral blood mononuclear cell (PBMNC) in vitro proliferative responses to 

mitogenic stimulation with phytohemagglutinin (PHA), concanavalin A (ConA), and pokeweed; naturalkiller cell (NKC) activity; delayed-type hypersensitivity (DHS) skin responses to recall antigens 

(tuberculin purified-protein derivative, mumps, tetanus toxoid, candida, trichophyton, streptokinase 

strepase, and coccidioidin); antibody responses to diptheria-tetanus and influenza vaccines); and 

hematological indices (complete blood counts, white blood cells, lymphocytes, granulocytes, platelets, 

erythrocytes, hematocrit, and hemoglobin concentration). For measurements repeated more than twice, 

the baseline value was subtracted from the value at each time point to calcuate within-subject changes, 

and two-way repeated measures analysis of variance was used to test for significant effects of dietary 

selenium and time. When the selenium main effect or the selenium x time interaction was significant, the 

Student-Newman-Keuls comparison test was used to identify significant differences between the lowselenium and high-selenium groups at individual time points. For measurements obtained only twice 

(during baseline and at end of study), within-subject changes were compared between groups with a twotailed ttest. Measurements obtained only at the end of the study were compared between groups with a 

two-tailed t-test without any correction. A probability of ≤0.05 was considered significant in all tests. 

Selenium levels in blood plasma began to change within 3 days of starting the low- and high-selenium 

diets and progressively continued throughout the study (Hawkes and Turek 2001). By week 17, mean 

plasma selenium concentrations had increased by 109% in the high-selenium group and decreased by 

38.5% in the low-selenium group. Group mean serum T3 concentrations (averages of within-subject 

changes from baseline) were significantly different in the low-selenium subjects and high-selenium 

subjects at all time points, but the magnitudes of the changes are insufficient to be considered biologically 

significant in either group. In the low-selenium group, serum T3 levels increased an average of 14 and 

8% from baseline during weeks 8 and 17, respectively. In the high-selenium group, serum T3 levels 

decreased an average of 23 and 11% from baseline during weeks 8 and 17, respectively. Analysis of 

variance (ANOVA) indicated a significant effect of dietary selenium on serum T3 concentrations and that 

the magnitude of the effect was modified by the duration of exposure (i.e., the group changes in T3 levels 

decreased over time). Although the decreases in serum T3 in the high selenium group and increases in 

serum T3 in the low selenium group lessened in magnitude during the study, all group mean values appear 

to have remained within the normal range (only week 17 values were actually reported). The respective 

baseline and week 17 serum T3 values (mean±SD) were 1.82±0.36 and 1.57±0.07 nmol/L in the highselenium group and 1.57±0.25 and 1.64±0.16 nmol/L in the low-selenium group, compared to a normal 

human range of 1.1–2.7 nM/L for total T3, indicating that the changes were subclinical and not 

biologically significant. Serum TSH concentrations increased significantly by 32% over its baseline 

concentration in the high-selenium group but did not change significantly in the low-selenium group. 
SELENIUM A-6 

APPENDIX A 

Baseline and ending TSH values in the high-selenium group were 2.25±0.81 and 2.96±1.05 mU/L, 

respectively, both of which are in the normal range of 0.3–4.0 mU/L (Stockigt 2000). There were no 

significant changes in the serum levels, nor any significant differences between groups in free or total 

testosterone, follicle-stimulating hormone, luteinizing hormone, prolactin, estradiol, or progesterone. 

The pattern of changes in seminal plasma selenium levels was similar to that observed for blood 

selenium, although selenium levels in sperm did not change significantly in either group (Hawkes and 

Turek 2001). Mean sperm motility (average of within-subject changes from baseline in fraction of motile 

sperm) was significantly different in the low-selenium subjects and high-selenium subjects at week 13, 

but not at weeks 8 or 17. The fraction of motile sperm increased an average of 10% in the low-selenium 

group at week 13, and was essentially the same as baseline at week 17. Sperm motility decreased an 

average of 32% in the high-selenium group at week 13, and ended 17% lower than the baseline value at 

week 17. The ANOVA indicated a significant effect of dietary selenium on sperm motility and that the 

effect of selenium was modified by duration of exposure (the groups diverged over time). Baseline and 

ending motile sperm fractions in the high-selenium group were 0.588±0.161 and 0.488±0.193, 

respectively; >50% motility is considered normal (FDA 1993). The decrease in sperm motility in the 

high-selenium group cannot be clearly attributed to exposure because the effect was not related to 

duration of treatment, and is unlikely to be adverse because the effect is at the low end of the normal 

range and not accompanied by any significant significant effects of high- or low-selenium treatment on 

sperm progression, concentration, total number, or morphology. Additionally, there were no effects of 

selenium on serum levels of the reproductive hormones, and changes in the thyroid hormones, which 

could also affect sperm function, were not outside normal ranges. 

The immunological assessment showed that the high-selenium diet was not immunotoxic and had some 

mild and transient immune-enhancing properties (Hawkes et al. 2001). There is an indication that 

selenium supplementation increased the secondary immune response to diphtheria vaccine when 

rechallenged at the end of the study. The mean within-subject ratio of diphtheria antibody titers 14 days 

after reinoculation (day 116) to titers 14 days after the initial challenge at baseline (day 19) was 

significantly greater in the high-selenium group than in the low-selenium group (2.7±1.8-fold vs. 

0.9±0.6-fold, p=0.03). Lymphocyte counts were significantly increased in the high-selenium group on 

day 45, but not at the end of the study, and there were no clear effects of selenium on numbers of 

activated or cytotoxic T-cells. The proliferative response of peripheral lymphocytes to stimulation with 

pokeweed mitogen (a B-cell mitogen) was significantly higher in the high-selenium group than in the 

low-selenium group on days 45 and 72, although not at the end of the study. There was no seleniuminduced lymphocyte proliferation in response to the T-cell mitogens (phytohemagglutinin or concanavalin 

A) or changes in any of the other immunological end points. The hematological assessment (Hawkes et 

al. 2001) found minor mean within-subject changes from baseline in white blood cell counts that were 

significantly different in the low- and high-selenium groups at the last two time points (days 70 and 99); 

WBCs were decreased by 5% in the high-selenium group and increased by 10% in the low-selenium 

group at the end of the study. The changes in WBC counts were due mainly to changes in granulocytes. 

Lymphocyte counts were significantly increased in the high-selenium group on day 45, but not at the end 

of the study. 

Chemical Manager: John Risher, Ph.D. 
SELENIUM B-1 

APPENDIX B. USER'S GUIDE 

Chapter 1 

Public Health Statement 

This chapter of the profile is a health effects summary written in non-technical language. Its intended 

audience is the general public especially people living in the vicinity of a hazardous waste site or 

chemical release. If the Public Health Statement were removed from the rest of the document, it would 

still communicate to the lay public essential information about the chemical. 

The major headings in the Public Health Statement are useful to find specific topics of concern. The 

topics are written in a question and answer format. The answer to each question includes a sentence that 

will direct the reader to chapters in the profile that will provide more information on the given topic. 

Chapter 2 

Relevance to Public Health 

This chapter provides a health effects summary based on evaluations of existing toxicologic, 

epidemiologic, and toxicokinetic information. This summary is designed to present interpretive, weightof-evidence discussions for human health end points by addressing the following questions. 

1. What effects are known to occur in humans? 

2. What effects observed in animals are likely to be of concern to humans? 

3. What exposure conditions are likely to be of concern to humans, especially around 

hazardous waste sites? 

The chapter covers end points in the same order they appear within the Discussion of Health Effects by 

Route of Exposure section, by route (inhalation, oral, dermal) and within route by effect. Human data are 

presented first, then animal data. Both are organized by duration (acute, intermediate, chronic). In vitro 

data and data from parenteral routes (intramuscular, intravenous, subcutaneous, etc.) are also considered 

in this chapter. If data are located in the scientific literature, a table of genotoxicity information is 

included. 

The carcinogenic potential of the profiled substance is qualitatively evaluated, when appropriate, using 

existing toxicokinetic, genotoxic, and carcinogenic data. ATSDR does not currently assess cancer 

potency or perform cancer risk assessments. Minimal risk levels (MRLs) for noncancer end points (if 

derived) and the end points from which they were derived are indicated and discussed. 

Limitations to existing scientific literature that prevent a satisfactory evaluation of the relevance to public 

health are identified in the Chapter 3 Data Needs section. 
SELENIUM B-2 

APPENDIX B 

Interpretation of Minimal Risk Levels 

Where sufficient toxicologic information is available, we have derived minimal risk levels (MRLs) for 

inhalation and oral routes of entry at each duration of exposure (acute, intermediate, and chronic). These 

MRLs are not meant to support regulatory action; but to acquaint health professionals with exposure 

levels at which adverse health effects are not expected to occur in humans. 

They should help physicians and public health officials determine the safety of a community living near a 

chemical emission, given the concentration of a contaminant in air or the estimated daily dose in water. 

MRLs are based largely on toxicological studies in animals and on reports of human occupational 

exposure. 

MRL users should be familiar with the toxicologic information on which the number is based. Chapter 2, 

"Relevance to Public Health," contains basic information known about the substance. Other sections such 

as Chapter 3 Section 3.9, "Interactions with Other Substances,” and Section 3.10, "Populations that are 

Unusually Susceptible" provide important supplemental information. 

MRL users should also understand the MRL derivation methodology. MRLs are derived using a 

modified version of the risk assessment methodology the Environmental Protection Agency (EPA) 

provides (Barnes and Dourson 1988) to determine reference doses for lifetime exposure (RfDs). 

To derive an MRL, ATSDR generally selects the most sensitive end point which, in its best judgement, 

represents the most sensitive human health effect for a given exposure route and duration. ATSDR 

cannot make this judgement or derive an MRL unless information (quantitative or qualitative) is available 

for all potential systemic, neurological, and developmental effects. If this information and reliable 

quantitative data on the chosen end point are available, ATSDR derives an MRL using the most sensitive 

species (when information from multiple species is available) with the highest NOAEL that does not 

exceed any adverse effect levels. When a NOAEL is not available, a lowest-observed-adverse-effect 

level (LOAEL) can be used to derive an MRL, and an uncertainty factor (UF) of 10 must be employed. 

Additional uncertainty factors of 10 must be used both for human variability to protect sensitive 

subpopulations (people who are most susceptible to the health effects caused by the substance) and for 

interspecies variability (extrapolation from animals to humans). In deriving an MRL, these individual 

uncertainty factors are multiplied together. The product is then divided into the inhalation concentration 

or oral dosage selected from the study. Uncertainty factors used in developing a substance-specific MRL 

are provided in the footnotes of the LSE Tables. 

Chapter 3 

Health Effects 

Tables and Figures for Levels of Significant Exposure (LSE) 

Tables (3-1, 3-2, and 3-3) and figures (3-1 and 3-2) are used to summarize health effects and illustrate 

graphically levels of exposure associated with those effects. These levels cover health effects observed at 

increasing dose concentrations and durations, differences in response by species, minimal risk levels 

(MRLs) to humans for noncancer end points, and EPA's estimated range associated with an upper- bound 

individual lifetime cancer risk of 1 in 10,000 to 1 in 10,000,000. Use the LSE tables and figures for a 

quick review of the health effects and to locate data for a specific exposure scenario. The LSE tables and 

figures should always be used in conjunction with the text. All entries in these tables and figures 

represent studies that provide reliable, quantitative estimates of No-Observed-Adverse-Effect Levels 

(NOAELs), Lowest-Observed-Adverse-Effect Levels (LOAELs), or Cancer Effect Levels (CELs). 
SELENIUM	 B-3 

APPENDIX B 

The legends presented below demonstrate the application of these tables and figures. Representative 

examples of LSE Table 3-1 and Figure 3-1 are shown. The numbers in the left column of the legends 

correspond to the numbers in the example table and figure. 

LEGEND 

See LSE Table 3-1 

(1) Route of Exposure One of the first considerations when reviewing the toxicity of a substance 

using these tables and figures should be the relevant and appropriate route of exposure. When 

sufficient data exists, three LSE tables and two LSE figures are presented in the document. The 

three LSE tables present data on the three principal routes of exposure, i.e., inhalation, oral, and 

dermal (LSE Table 3-1, 3-2, and 3-3, respectively). LSE figures are limited to the inhalation 

(LSE Figure 3-1) and oral (LSE Figure 3-2) routes. Not all substances will have data on each 

route of exposure and will not therefore have all five of the tables and figures. 

(2) Exposure Period Three exposure periods - acute (less than 15 days), intermediate (15–364 days), 

and chronic (365 days or more) are presented within each relevant route of exposure. In this 

example, an inhalation study of intermediate exposure duration is reported. For quick reference 

to health effects occurring from a known length of exposure, locate the applicable exposure 

period within the LSE table and figure. 

(3) Health Effect The major categories of health effects included in LSE tables and figures are death, 

systemic, immunological, neurological, developmental, reproductive, and cancer. NOAELs and 

LOAELs can be reported in the tables and figures for all effects but cancer. Systemic effects are 

further defined in the "System" column of the LSE table (see key number 18). 

(4) Key to Figure Each key number in the LSE table links study information to one or more data 

points using the same key number in the corresponding LSE figure. In this example, the study 

represented by key number 18 has been used to derive a NOAEL and a Less Serious LOAEL 

(also see the 2 "18r" data points in Figure 3-1). 

(5) Species The test species, whether animal or human, are identified in this column. Chapter 2, 

"Relevance to Public Health," covers the relevance of animal data to human toxicity and 

Section 3.4, "Toxicokinetics," contains any available information on comparative toxicokinetics. 

Although NOAELs and LOAELs are species specific, the levels are extrapolated to equivalent 

human doses to derive an MRL. 

(6) Exposure Frequency/Duration The duration of the study and the weekly and daily exposure 

regimen are provided in this column. This permits comparison of NOAELs and LOAELs from 

different studies. In this case (key number 18), rats were exposed to 1,1,2,2-tetrachloroethane via 

inhalation for 6 hours per day, 5 days per week, for 3 weeks. For a more complete review of the 

dosing regimen refer to the appropriate sections of the text or the original reference paper, i.e., 

Nitschke et al. 1981. 

(7) System This column further defines the systemic effects. These systems include: respiratory, 

cardiovascular, gastrointestinal, hematological, musculoskeletal, hepatic, renal, and 

dermal/ocular. "Other" refers to any systemic effect (e.g., a decrease in body weight) not covered 

in these systems. In the example of key number 18, 1 systemic effect (respiratory) was 

investigated. 
SELENIUM	 B-4 

APPENDIX B 

(8) NOAEL A No-Observed-Adverse-Effect Level (NOAEL) is the highest exposure level at which 

no harmful effects were seen in the organ system studied. Key number 18 reports a NOAEL of 

3 ppm for the respiratory system which was used to derive an intermediate exposure, inhalation 

MRL of 0.005 ppm (see footnote "b"). 

(9) LOAEL A Lowest-Observed-Adverse-Effect Level (LOAEL) is the lowest dose used in the study 

that caused a harmful health effect. LOAELs have been classified into "Less Serious" and 

"Serious" effects. These distinctions help readers identify the levels of exposure at which adverse 

health effects first appear and the gradation of effects with increasing dose. A brief description of 

the specific end point used to quantify the adverse effect accompanies the LOAEL. The 

respiratory effect reported in key number 18 (hyperplasia) is a Less serious LOAEL of 10 ppm. 

MRLs are not derived from Serious LOAELs. 

(10) Reference The complete reference citation is given in Chapter 9 of the profile. 

(11)	 CEL A Cancer Effect Level (CEL) is the lowest exposure level associated with the onset of 

carcinogenesis in experimental or epidemiologic studies. CELs are always considered serious 

effects. The LSE tables and figures do not contain NOAELs for cancer, but the text may report 

doses not causing measurable cancer increases. 

(12)	 Footnotes Explanations of abbreviations or reference notes for data in the LSE tables are found in 

the footnotes. Footnote "b" indicates the NOAEL of 3 ppm in key number 18 was used to derive 

an MRL of 0.005 ppm. 

LEGEND 

See Figure 3-1 

LSE figures graphically illustrate the data presented in the corresponding LSE tables. Figures 

help the reader quickly compare health effects according to exposure concentrations for particular 

exposure periods. 

(13)	 Exposure Period The same exposure periods appear as in the LSE table. In this example, health 

effects observed within the intermediate and chronic exposure periods are illustrated. 

(14) Health Effect These are the categories of health effects for which reliable quantitative data exists. 

The same health effects appear in the LSE table. 

(15)	 Levels of Exposure concentrations or doses for each health effect in the LSE tables are 

graphically displayed in the LSE figures. Exposure concentration or dose is measured on the log 

scale "y" axis. Inhalation exposure is reported in mg/m3

 or ppm and oral exposure is reported in 

mg/kg/day. 

(16)	 NOAEL In this example, the open circle designated 18r identifies a NOAEL critical end point in 

the rat upon which an intermediate inhalation exposure MRL is based. The key number 18 

corresponds to the entry in the LSE table. The dashed descending arrow indicates the 

extrapolation from the exposure level of 3 ppm (see entry 18 in the Table) to the MRL of 

0.005 ppm (see footnote "b" in the LSE table). 
SELENIUM	 B-5 

APPENDIX B 

(17)	 CEL Key number 38r is 1 of 3 studies for which Cancer Effect Levels were derived. The 

diamond symbol refers to a Cancer Effect Level for the test species-mouse. The number 38 

corresponds to the entry in the LSE table. 

(18)	 Estimated Upper-Bound Human Cancer Risk Levels This is the range associated with the upperbound for lifetime cancer risk of 1 in 10,000 to 1 in 10,000,000. These risk levels are derived 

from the EPA's Human Health Assessment Group's upper-bound estimates of the slope of the 

cancer dose response curve at low dose levels (q1*). 

(19)	 Key to LSE Figure The Key explains the abbreviations and symbols used in the figure. 
SAMPLE 

1 → TABLE 3-1. Levels of Significant Exposure to [Chemical x] - Inhalation 

Exposure LOAEL (effect) 

Key to frequency/ NOAEL figurea Species duration System (ppm) Less serious (ppm) Serious (ppm) 

2 → INTERMEDIATE EXPOSURE 

5 6 7 8 9 

3 → Systemic ↓ ↓ ↓ ↓ ↓ 

3b 18 Rat 13 wk Resp 10 (hyperplasia) 

4 → 5 d/wk 

6 hr/d 

CHRONIC EXPOSURE 

Cancer 11 

↓

38 Rat 18 mo 20 (CEL, multiple organs) 

5 d/wk 7 hr/d 

39 Rat 89-104 wk 10 (CEL, lung tumors, nasal 

5 d/wk tumors) 

6 hr/d 

40 Mouse 79-103 wk 10 (CEL, lung tumors, 

5 d/wk hemangiosarcomas) 

6 hr/d 

a 12 → The number corresponds to entries in Figure 3-1. b Used to derive an intermediate inhalation Minimal Risk Level (MRL) of 5 x 10-3 ppm; dose adjusted for intermittent ex

by an uncertainty factor of 100 (10 for extrapolation from animal to humans, 10 for human variability). 

	 	

	 

SELENIUM B-8 

APPENDIX B 
SELENIUM C-1 

APPENDIX C. ACRONYMS, ABBREVIATIONS, AND SYMBOLS 

ACOEM American College of Occupational and Environmental Medicine 

ACGIH American Conference of Governmental Industrial Hygienists 

ADI acceptable daily intake 

ADME absorption, distribution, metabolism, and excretion 

AED atomic emission detection 

AOEC Association of Occupational and Environmental Clinics 

AFID alkali flame ionization detector 

AFOSH Air Force Office of Safety and Health 

ALT alanine aminotransferase 

AML acute myeloid leukemia 

ANOVA analysis of variance 

AOAC Association of Official Analytical Chemists 

AP alkaline phosphatase 

APHA American Public Health Association 

AST aspartate aminotranferase 

atm atmosphere 

ATSDR Agency for Toxic Substances and Disease Registry 

AWQC Ambient Water Quality Criteria 

BAT best available technology 

BCF bioconcentration factor 

BEI Biological Exposure Index 

BSC Board of Scientific Counselors 

C centigrade 

CAA Clean Air Act 

CAG Cancer Assessment Group of the U.S. Environmental Protection Agency 

CAS Chemical Abstract Services 

CDC Centers for Disease Control and Prevention 

CEL cancer effect level 

CELDS Computer-Environmental Legislative Data System 

CERCLA Comprehensive Environmental Response, Compensation, and Liability Act 

CFR Code of Federal Regulations 

Ci curie 

CI confidence interval 

CL ceiling limit value 

CLP Contract Laboratory Program 

cm centimeter 

CML chronic myeloid leukemia 

CPSC Consumer Products Safety Commission 

CWA Clean Water Act 

DHEW Department of Health, Education, and Welfare 

DHHS Department of Health and Human Services 

DNA deoxyribonucleic acid 

DOD Department of Defense 

DOE Department of Energy 

DOL Department of Labor 

DOT Department of Transportation 
SELENIUM C-2 

APPENDIX C 

DOT/UN/ Department of Transportation/United Nations/ 

NA/IMCO North America/International Maritime Dangerous Goods Code 

DWEL drinking water exposure level 

ECD electron capture detection 

ECG/EKG electrocardiogram 

EEG electroencephalogram 

EEGL Emergency Exposure Guidance Level 

EPA Environmental Protection Agency 

F Fahrenheit 

F1 first-filial generation 

FAO Food and Agricultural Organization of the United Nations 

FDA Food and Drug Administration 

FEMA Federal Emergency Management Agency 

FIFRA Federal Insecticide, Fungicide, and Rodenticide Act 

FPD flame photometric detection 

fpm feet per minute 

FR Federal Register 

FSH follicle stimulating hormone 

g gram 

GC gas chromatography 

gd gestational day 

GLC gas liquid chromatography 

GPC gel permeation chromatography 

GPX glutathione peroxidase 

GSH glutathione 

HPLC high-performance liquid chromatography 

HRGC high resolution gas chromatography 

HSDB Hazardous Substance Data Bank 

IARC International Agency for Research on Cancer 

IDLH immediately dangerous to life and health 

ILO International Labor Organization 

IRIS Integrated Risk Information System 

Kd adsorption ratio 

kg kilogram 

Koc organic carbon partition coefficient 

Kow octanol-water partition coefficient 

L liter 

LC liquid chromatography 

LCLo lethal concentration, low 

LC50 lethal concentration, 50% kill 

LDLo lethal dose, low 

LD50 lethal dose, 50% kill 

LDH lactic dehydrogenase 

LH luteinizing hormone 

LT50 lethal time, 50% kill 

LOAEL lowest-observed-adverse-effect level 

LSE Levels of Significant Exposure 

m meter 

MA trans,trans-muconic acid 

MAL maximum allowable level 

mCi millicurie 
SELENIUM C-3 

APPENDIX C 

MCL maximum contaminant level 

MCLG maximum contaminant level goal 

MFO mixed function oxidase 

mg milligram 

mL milliliter 

mm millimeter 

mmHg millimeters of mercury 

mmol millimole 

mppcf millions of particles per cubic foot 

MRL Minimal Risk Level 

MS mass spectrometry 

NAAQS National Ambient Air Quality Standard 

NAS National Academy of Science 

NATICH National Air Toxics Information Clearinghouse 

NATO North Atlantic Treaty Organization 

NCE normochromatic erythrocytes 

NCEH National Center for Environmental Health 

NCI National Cancer Institute 

ND not detected 

NFPA National Fire Protection Association 

ng nanogram 

NIEHS National Institute of Environmental Health Sciences 

NIOSH National Institute for Occupational Safety and Health 

NIOSHTIC NIOSH's Computerized Information Retrieval System 

NLM National Library of Medicine 

nm nanometer 

NHANES National Health and Nutrition Examination Survey 

nmol nanomole 

NOAEL no-observed-adverse-effect level 

NOES National Occupational Exposure Survey 

NOHS National Occupational Hazard Survey 

NPD nitrogen phosphorus detection 

NPDES National Pollutant Discharge Elimination System 

NPL National Priorities List 

NR not reported 

NRC National Research Council 

NS not specified 

NSPS New Source Performance Standards 

NTIS National Technical Information Service 

NTP National Toxicology Program 

ODW Office of Drinking Water, EPA 

OERR Office of Emergency and Remedial Response, EPA 

OHM/TADS Oil and Hazardous Materials/Technical Assistance Data System 

OPP Office of Pesticide Programs, EPA 

OPPTS Office of Prevention, Pesticides and Toxic Substances, EPA 

OPPT Office of Pollution Prevention and Toxics, EPA 

OR odds ratio 

OSHA Occupational Safety and Health Administration 

OSW Office of Solid Waste, EPA 

OW Office of Water 

OWRS Office of Water Regulations and Standards, EPA 
SELENIUM C-4 

APPENDIX C 

PAH polycyclic aromatic hydrocarbon 

PBPD physiologically based pharmacodynamic 

PBPK physiologically based pharmacokinetic 

PCE polychromatic erythrocytes 

PEL permissible exposure limit 

pg pictogram 

PHS Public Health Service 

PID photo ionization detector 

pmol picomole 

PMR proportionate mortality ratio 

ppb parts per billion 

ppm parts per million 

ppt parts per trillion 

PSNS pretreatment standards for new sources 

RBC red blood cell 

RDA Recommended Daily Allowance 

REL recommended exposure level/limit 

RfC reference concentration 

RfD reference dose 

RNA ribonucleic acid 

RR relative risk 

RTECS Registry of Toxic Effects of Chemical Substances 

RQ reportable quantity 

SARA Superfund Amendments and Reauthorization Act 

SCE sister chromatid exchange 

SGOT serum glutamic oxaloacetic transaminase 

SGPT serum glutamic pyruvic transaminase 

SIC standard industrial classification 

SIM selected ion monitoring 

SMCL secondary maximum contaminant level 

SMR standardized mortality ratio 

SNARL suggested no adverse response level 

SPEGL Short-Term Public Emergency Guidance Level 

STEL short term exposure limit 

STORET Storage and Retrieval T3 triiodothyronine T4 thyroxine 

TD50 toxic dose, 50% specific toxic effect 

TLV threshold limit value 

TOC total organic carbon 

TPQ threshold planning quantity 

TRI Toxics Release Inventory 

TSCA Toxic Substances Control Act 

TSH thyroid stimulating hormone 

TWA time-weighted average 

UF uncertainty factor 

UL Tolerable Upper Intake Level 

U.S. United States 

USDA United States Department of Agriculture 

USGS United States Geological Survey 

VOC volatile organic compound 
SELENIUM C-5 

WBC 

WHO 

> $

= 

< #

% αβγδ

μm

μg q1

* 

– 

+ 

(+) 

(–) 

APPENDIX C 

white blood cell 

World Health Organization 

greater than 

greater than or equal to 

equal to 

less than 

less than or equal to 

percent 

alpha 

beta 

 gamma 

delta 

 micrometer 

microgram 

cancer slope factor 

negative 

positive 

weakly positive result 

weakly negative result