TOXICOLOGICAL PROFILE FOR 

TIN AND TIN COMPOUNDS 

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES 

Public Health Service 

Agency for Toxic Substances and Disease Registry
 

August 2005 
TIN AND TIN COMPOUNDS 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. 
TIN AND TIN COMPOUNDS iii 

UPDATE STATEMENT 

A Toxicological Profile for Tin and Tin Compounds, Draft for Public Comment was released in 

September 2003. This edition supersedes any previously released draft or final profile. 

Toxicological profiles are revised and republished as necessary. 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 F-32 

Atlanta, Georgia 30333 


TIN AND TIN COMPOUNDS vi 

*Legislative Background 

The toxicological profiles are developed in response to the Superfund Amendments and Reauthorization 

Act (SARA) of 1986 (Public law 99-499) which amended the Comprehensive Environmental Response, 

Compensation, and Liability Act of 1980 (CERCLA or Superfund). This public law directed ATSDR to 

prepare toxicological profiles for hazardous substances most commonly found at facilities on the 

CERCLA National Priorities List and that pose the most significant potential threat to human health, as 

determined by ATSDR and the EPA. The availability of the revised priority list of 275 hazardous 

substances was announced in the Federal Register on November 17, 1997 (62 FR 61332). For prior 

versions of the list of substances, see Federal Register notices dated April 29, 1996 (61 FR 18744); April 

17, 1987 (52 FR 12866); October 20, 1988 (53 FR 41280); October 26, 1989 (54 FR 43619); October 17, 

1990 (55 FR 42067); October 17, 1991 (56 FR 52166); October 28, 1992 (57 FR 48801); and February 

28, 1994 (59 FR 9486). Section 104(i)(3) of CERCLA, as amended, directs the Administrator of ATSDR 

to prepare a toxicological profile for each substance on the list. 
TIN AND TIN COMPOUNDS 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: (770) 488-4178

 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. 
TIN AND TIN COMPOUNDS 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. 
TIN AND TIN COMPOUNDS ix 

CONTRIBUTORS 

CHEMICAL MANAGER(S)/AUTHOR(S): 

Carolyn Harper, Ph.D. 

ATSDR, Division of Toxicology, Atlanta, GA 

Fernando Llados, Ph.D. 

Gary Diamond, Ph.D. 

Lara L. Chappell, Ph.D. 

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. 

4. Green Border Review. Green Border review assures the consistency with ATSDR policy. 

TIN AND TIN COMPOUNDS xi 

PEER REVIEW 

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

1. Michael Aschner, Ph.D., Wake Forest University School of Medicine, Winston-Salem, North 

Carolina; 

2. Olen Brown, Ph.D., University of Missouri-Columbia, Columbia, Missouri; and 

3. Bruce Jarnot, Ph.D., DABT, American Petroleum Institute, Washington, DC. 

These experts collectively have knowledge of tin'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. 

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. 

 

 

TIN AND TIN COMPOUNDS xiii 

CONTENTS
 

DISCLAIMER ..............................................................................................................................................ii 

UPDATE STATEMENT .............................................................................................................................iii 

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

QUICK REFERENCE FOR HEALTH CARE PROVIDERS....................................................................vii 

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

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

CONTENTS...............................................................................................................................................xiii 

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

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

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

1.1 WHAT ARE TIN AND TIN COMPOUNDS? ...........................................................................1 

1.2 WHAT HAPPENS TO TIN AND TIN COMPOUNDS WHEN THEY ENTER THE 

 ENVIRONMENT? ......................................................................................................................2 

1.3 HOW MIGHT I BE EXPOSED TO TIN AND TIN COMPOUNDS? .......................................3 

1.4 HOW CAN TIN AND TIN COMPOUNDS ENTER AND LEAVE MY BODY? ....................4 

1.5 HOW CAN TIN AND TIN COMPOUNDS AFFECT MY HEALTH? .....................................5 

1.6 HOW CAN TIN AND TIN COMPOUNDS AFFECT CHILDREN? ........................................6 

1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO TIN AND TIN 

COMPOUNDS? ..........................................................................................................................7 

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

EXPOSED TO TIN AND TIN COMPOUNDS? ........................................................................8 

1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO 

PROTECT HUMAN HEALTH?.................................................................................................8 

1.10 WHERE CAN I GET MORE INFORMATION? .....................................................................10 

2. RELEVANCE TO PUBLIC HEALTH .................................................................................................11
 

2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO TIN AND TIN 

COMPOUNDS IN THE UNITED STATES.............................................................................11 

2.2 SUMMARY OF HEALTH EFFECTS......................................................................................12 

2.3 MINIMAL RISK LEVELS .......................................................................................................16 

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

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

3.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE ..................................23 

3.2.1 Inhalation Exposure ..............................................................................................................24 

3.2.1.1 Death ............................................................................................................................25 

3.2.1.2 Systemic Effects...........................................................................................................30 

3.2.1.3 Immunological and Lymphoreticular Effects...............................................................34 

3.2.1.4 Neurological Effects.....................................................................................................34 

3.2.1.5 Reproductive Effects....................................................................................................35 

3.2.1.6 Developmental Effects .................................................................................................36 

3.2.1.7 Cancer........................................................................................................................... 36 

3.2.2 Oral Exposure........................................................................................................................36 

3.2.2.1 Death ............................................................................................................................36 

3.2.2.2 Systemic Effects.........................................................................................................114 

3.2.2.3 Immunological and Lymphoreticular Effects.............................................................131 

3.2.2.4 Neurological Effects...................................................................................................135 
 

 

 

TIN AND TIN COMPOUNDS xiv 

3.2.2.5 Reproductive Effects..................................................................................................140 

3.2.2.6 Developmental Effects ...............................................................................................144
 

3.2.2.7 Cancer.........................................................................................................................149 

3.2.3 Dermal Exposure.................................................................................................................152 

3.2.3.1 Death ..........................................................................................................................152 

3.2.3.2 Systemic Effects.........................................................................................................155 

3.2.3.3 Immunological and Lymphoreticular Effects.............................................................157 

3.2.3.4 Neurological Effects...................................................................................................158 

3.2.3.5 Reproductive Effects..................................................................................................158 

3.2.3.6 Developmental Effects ...............................................................................................158
 

3.2.3.7 Cancer.........................................................................................................................158 

3.2.4 Other Routes of Exposure ...................................................................................................159 

3.3 GENOTOXICITY ...................................................................................................................161 

3.4 TOXICOKINETICS................................................................................................................168 

3.4.1 Absorption...........................................................................................................................168 

3.4.1.1 Inhalation Exposure....................................................................................................171 

3.4.1.2 Oral Exposure.............................................................................................................171 

3.4.1.3 Dermal Exposure ........................................................................................................173 

3.4.2 Distribution .........................................................................................................................173 

3.4.2.1 Inhalation Exposure....................................................................................................175 

3.4.2.2 Oral Exposure.............................................................................................................175 

3.4.2.3 Dermal Exposure ........................................................................................................179 

3.4.2.4 Other Routes of Exposure ..........................................................................................179
 

3.4.3 Metabolism..........................................................................................................................180 

3.4.4 Elimination and Excretion...................................................................................................181 

3.4.4.1 Inhalation Exposure....................................................................................................181 

3.4.4.2 Oral Exposure.............................................................................................................182 

3.4.4.3 Dermal Exposure ........................................................................................................183 

3.4.4.4 Other Routes of Exposure ..........................................................................................183
 

3.4.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models ...........186 

3.5 MECHANISMS OF ACTION ................................................................................................191 

3.5.1 Pharmacokinetic Mechanisms.............................................................................................191
 

3.5.2 Mechanisms of Toxicity......................................................................................................193 

3.5.3 Animal-to-Human Extrapolations.......................................................................................196
 

3.6 TOXICITIES MEDIATED THROUGH THE NEUROENDOCRINE AXIS ........................197 

3.7 CHILDREN’S SUSCEPTIBILITY.........................................................................................202 

3.8 BIOMARKERS OF EXPOSURE AND EFFECT ..................................................................205 

3.8.1 Biomarkers Used to Identify or Quantify Exposure to Tin and Tin Compounds................206 

3.8.2 Biomarkers Used to Characterize Effects Caused by Tin and Tin Compounds..................206 

3.9 INTERACTIONS WITH OTHER CHEMICALS ..................................................................207 

3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE.............................................209 

3.11 METHODS FOR REDUCING TOXIC EFFECTS.................................................................209 

3.11.1 Reducing Peak Absorption Following Exposure ............................................................210 

3.11.2 Reducing Body Burden...................................................................................................210 

3.11.3 Interfering with the Mechanism of Action for Toxic Effects .........................................210 

3.12 ADEQUACY OF THE DATABASE......................................................................................211 

3.12.1 Existing Information on Health Effects of Tin and Tin Compounds..............................211 

3.12.2 Identification of Data Needs ...........................................................................................214 

3.12.3 Ongoing Studies..............................................................................................................226 
TIN AND TIN COMPOUNDS xv 

4. CHEMICAL AND PHYSICAL INFORMATION..............................................................................227 

4.1 CHEMICAL IDENTITY.........................................................................................................227 

4.2 PHYSICAL AND CHEMICAL PROPERTIES......................................................................227 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL..........................................................243 

5.1 PRODUCTION .......................................................................................................................243 

5.2 IMPORT/EXPORT .................................................................................................................246 

5.3 USE..........................................................................................................................................246 

5.4 DISPOSAL..............................................................................................................................248 

6. POTENTIAL FOR HUMAN EXPOSURE .........................................................................................249 

6.1 OVERVIEW............................................................................................................................249 

6.2 RELEASES TO THE ENVIRONMENT................................................................................253 

6.2.1 Air .......................................................................................................................................253 

6.2.2 Water...................................................................................................................................254 

6.2.3 Soil ......................................................................................................................................255 

6.3 ENVIRONMENTAL FATE....................................................................................................256
 

6.3.1 Transport and Partitioning...................................................................................................256 

6.3.2 Transformation and Degradation ........................................................................................259
 

6.3.2.1 Air...............................................................................................................................259 

6.3.2.2 Water ..........................................................................................................................259 

6.3.2.3 Sediment and Soil.......................................................................................................260 

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT...............................260 

6.4.1 Air .......................................................................................................................................261 

6.4.2 Water...................................................................................................................................261 

6.4.3 Sediment and Soil ...............................................................................................................265 

6.4.4 Other Environmental Media................................................................................................269 

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE .....................................282 

6.6 EXPOSURES OF CHILDREN...............................................................................................284 

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES ...........................................285 

6.8 ADEQUACY OF THE DATABASE......................................................................................286 

6.8.1 Identification of Data Needs ...............................................................................................286 

6.8.2 Ongoing Studies ..................................................................................................................289 

7. ANALYTICAL METHODS ...............................................................................................................291 

7.1 BIOLOGICAL MATERIALS................................................................................................. 292 

7.2 ENVIRONMENTAL SAMPLES............................................................................................292 

7.3 ADEQUACY OF THE DATABASE......................................................................................297 

7.3.1 Identification of Data Needs ...............................................................................................298 

7.3.2 Ongoing Studies ..................................................................................................................299 

8. REGULATIONS AND ADVISORIES ...............................................................................................301
 

9. REFERENCES ....................................................................................................................................309 

10. GLOSSARY ......................................................................................................................................371 
TIN AND TIN COMPOUNDS xvi 

APPENDICES 

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

B. USER'S GUIDE ..................................................................................................................................B-1 

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

D. INDEX ................................................................................................................................................D-1 
TIN AND TIN COMPOUNDS xvii 

LIST OF FIGURES 

3-1. Levels of Significant Exposure to Tributyltins—Inhalation............................................................... 28
 

3-2. Levels of Significant Exposure to Inorganic Tin—Oral..................................................................... 48
 

3-3. Levels of Significant Exposure to Dibutyltins—Oral......................................................................... 59 

3-4. Levels of Significant Exposure to Dioctyltins—Oral......................................................................... 66 

3-5. Levels of Significant Exposure to Triphenyltins—Oral ..................................................................... 77
 

3-6. Levels of Significant Exposure to Triethyltins—Oral........................................................................ 83 

3-7. Levels of Significant Exposure to Trimethyltins—Oral..................................................................... 90
 

3-8. Levels of Significant Exposure to Tributyltins—Oral...................................................................... 107
 

3-9. Conceptual Representation of a Physiologically Based Pharmacokinetic (PBPK) Model for a
 

Hypothetical Chemical Substance .....................................................................................................186
 

3-10. ICRP (1981b, 2001) Tin Biokinetic Model ....................................................................................187
 

3-11. Existing Information on Health Effects of Inorganic Tin Compounds...........................................210
 

3-12. Existing Information on Health Effects of Organotin Compounds................................................211
 

6-1. Frequency of NPL Sites with Tin Contamination ............................................................................250
 

6-2. Frequency of NPL Sites with Organotin Contamination..................................................................251
 

TIN AND TIN COMPOUNDS xix 

LIST OF TABLES 

3-1. Levels of Significant Exposure to Tributyltins—Inhalation............................................................... 26
 

3-2. Levels of Significant Exposure to Inorganic Tin—Oral..................................................................... 37
 

3-3. Levels of Significant Exposure to Dibutyltins—Oral......................................................................... 52 

3-4. Levels of Significant Exposure to Dioctyltins—Oral......................................................................... 62 

3-5. Levels of Significant Exposure to Triphenyltins—Oral ..................................................................... 68
 

3-6. Levels of Significant Exposure to Triethyltins—Oral........................................................................ 80 

3-7. Levels of Significant Exposure to Trimethyltins—Oral..................................................................... 85
 

3-8. Levels of Significant Exposure to Tributyltins—Oral........................................................................ 92 

3-9. Levels of Significant Exposure to Tributyltins—Dermal................................................................. 153
 

3-10. Genotoxicity of Inorganic Tin Compounds In Vitro ......................................................................162
 

3-11. Genotoxicity of Organotin Compounds In Vitro ............................................................................163
 

3-12. Genotoxicity of Organotin Compounds In Vivo .............................................................................168
 

3-13. Mean Tin Levels in Human Tissues...............................................................................................172
 

4-1. Chemical Identity of Tin and Tin Compounds.................................................................................228
 

4-2. Physical and Chemical Properties of Tin and Tin Compounds ........................................................237
 

5-1. Current U.S. Manufacturers of Selected Tin Compounds................................................................244
 

6-1. Conversion Between Mass on a Tin Basis to Mass on an Organotin Cation Basis..........................262
 

6-2. Organotin Levels in Sediment ..........................................................................................................267
 

6-3. Tin Levels in Food............................................................................................................................270
 

6-4. Tributyltin (TBT) Levels in Food.....................................................................................................272
 

6-5. Tin and Organotin Levels in Human Tissues and Fluids..................................................................277
 

6-6. Ongoing Studies on Organotin Compounds.....................................................................................290
 

7-1. Analytical Methods for Determining Inorganic Tin and Organotin Compounds in Biological 

Materials ............................................................................................................................................293
 
TIN AND TIN COMPOUNDS xx 

7-2. Analytical Methods for Determining Inorganic Tin and Organotin Compounds in 

 Environmental Samples.....................................................................................................................295
 

8-1. Regulations and Guidelines Applicable to Tin and Tin Compounds ...............................................302
 
TIN AND TIN COMPOUNDS 1 

1. PUBLIC HEALTH STATEMENT 

This public health statement tells you about tin and tin compounds and the effects of exposure to 

them. 

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

the nation. These sites are then placed on the National Priorities List (NPL) and are targeted for 

long-term federal clean-up activities. Tin and organotin compounds have been found in at least 

214 and 8, respectively, of the 1,662 current or former NPL sites. Although the total number of 

NPL sites evaluated for these substances is not known, the possibility exists that the number of 

sites at which tin and organotin compounds are found may increase in the future as more sites are 

evaluated. This information is important because these sites may be sources of exposure and 

exposure to these substances may harm you. 

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

container, such as a drum or bottle, it enters the environment. Such a release does not always 

lead to exposure. You can be 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 tin and tin compounds, many factors will determine whether you will be 

harmed. These factors include the dose (how much), the duration (how long), and how you 

come in contact with them. You must also consider any other chemicals you are exposed to and 

your age, sex, diet, family traits, lifestyle, and state of health. 

1.1 WHAT ARE TIN AND TIN COMPOUNDS? 

Tin is a soft, white, silvery metal that is insoluble in water. Tin metal is used to line cans for 

food, beverages, and aerosols. It is present in brass, bronze, pewter, and some soldering 

materials. 
TIN AND TIN COMPOUNDS 2 

1. PUBLIC HEALTH STATEMENT 

Tin is a metal that can combine with other chemicals to form various compounds. When tin is 

combined with chlorine, sulfur, or oxygen, it is called an inorganic tin compound. Inorganic tin 

compounds are found in small amounts in the earth's crust. They are also present in toothpaste, 

perfumes, soaps, coloring agents, food additives, and dyes. 

Tin also can combine with carbon to form organotin compounds. These compounds are used in 

making plastics, food packages, plastic pipes, pesticides, paints, wood preservatives, and rodent 

(rats and mice) repellants. 

There can be tin metal as well as inorganic and organic tin compounds in the air, water, and soil 

near places where they are naturally present in the rocks, mined, manufactured, or used. In 

general, organic tin compounds are from human-made sources and do not occur naturally in the 

environment. The time each tin compound stays in air, water, or soil differs from compound to 

compound. 

Further information on the properties and uses of tin and its compounds and how they behave in 

the environment is found in Chapters 4, 5, and 6. 

1.2 WHAT HAPPENS TO TIN AND TIN COMPOUNDS WHEN THEY ENTER THE 

ENVIRONMENT? 

Tin is a component of many soils. Tin may be released in dusts from wind storms, roads, and 

farming activities. Gases, dusts, and fumes containing tin may be released from smelting and 

refining processes, burning of waste, and burning of fossil fuels (coal or oil). Particles in the air 

containing tin may be transported by wind or washed out of the air by rain or snow. Tin binds to 

soils and to sediments in water and is generally regarded as being relatively immobile in the 

environment. Tin cannot be destroyed in the environment. It can only change its form or 

become attached or separated from particles in soil, sediment, and water. 

Organic tin compounds stick to soil, sediment, and particles in water. Organic tin compounds 

can be degraded (by exposure to sunlight and by bacteria) into inorganic tin compounds. In 
TIN AND TIN COMPOUNDS 3 

1. PUBLIC HEALTH STATEMENT 

water, organic tin compounds are mostly attached to particles in water. Organic tin compounds 

may also settle out of the water into sediments and may remain unchanged for years. Organic tin 

compounds may be taken up into the tissues of animals that live in water containing these 

compounds. 

1.3 HOW MIGHT I BE EXPOSED TO TIN AND TIN COMPOUNDS? 

Tin is present in the air, water, soil, and landfills and is a normal part of many plants and animals 

that live on land and in water. Tin is also present in the tissues of your body. There is no 

evidence that tin is an essential element for humans. 

Since tin is naturally found in soils, it will be found in small amounts in foods. Tin 

concentrations of vegetables, fruits and fruit juices, nuts, dairy products, meat, fish, poultry, 

eggs, beverages, and other foods not packaged in metal cans are generally less than 2 parts per 

million (ppm) (1 ppm = 1 part of tin in a million parts of food by weight). Tin concentrations in 

pastas and breads have been reported to range from less than 0.003 to 0.03 ppm. You can be 

exposed to tin when you eat food or drink juice or other liquids from tin-lined cans. Canned 

food from lacquered tin-lined cans contains less than 25 ppm of tin since the lacquer prevents the 

food from reacting with the tin. Food from unlacquered tin-lined cans contains up to 100 ppm of 

tin since the reaction of the food with the can causes some of the tin to dissolve in the contents of 

the can. Greater than 90% of tin-lined cans used for food today are lacquered. Only light 

colored fruit and fruit juices are packed in unlacquered tin-lined cans, since tin helps maintain 

the color of the fruit. Tin concentrations in food also increase if food is stored in opened cans. 

Stannous fluoride, a tin-containing compound, is added to toothpaste. 

You can also be exposed to higher-than-normal levels of tin if you work in a factory that makes 

or uses tin. Because tin compounds have many uses, you can be exposed by breathing in tin 

dusts or fumes or getting tin compounds on your skin. Tin compounds can also be spilled 

accidentally. If you live near a hazardous waste site, you could be exposed by breathing dusts, 

touching materials, or drinking water contaminated with tin. 
TIN AND TIN COMPOUNDS 4 

1. PUBLIC HEALTH STATEMENT 

Humans are usually exposed to tin at far less than 1 ppm from air and water. The amounts in air 

and water near hazardous waste sites could be higher. 

Young children sometimes eat soil during play. While most soil contains about 1 ppm tin, some 

soils may contain as much as 200 ppm tin. Assuming that children eat 200 mg of soil per day, 

exposure to tin from eating soil would be low. 

You may be exposed to organic tin compounds (mainly butyltin compounds) by eating seafood 

from coastal waters or from contact with household products that contain organotin compounds, 

(polyurethane, plastic polymers, and silicon-coated baking parchment paper). Organic tin 

compounds have been detected in drinking water in Canada where pipes made of polyvinyl 

chloride (PVC), which contain organic tin compounds, are used in the distribution of drinking 

water. 

Additional information on how you can be exposed to tin compounds is given in Chapter 6. 

1.4 HOW CAN TIN AND TIN COMPOUNDS ENTER AND LEAVE MY BODY? 

Tin can enter your body when you eat contaminated food or drink contaminated water, when you 

touch or eat soil that has tin in it, or when you breathe tin-containing fumes or dusts. Tin 

compounds can enter your body from nearby hazardous waste sites by exposure to contaminated 

air, water, and soil. When you eat tin in your food, very little leaves the gastrointestinal tract and 

gets into your bloodstream. Most tin travels through the intestines and leaves your body in the 

feces. Some leaves your body in the urine. If you breathe air containing tin dust or fumes, some 

of the tin could be trapped in your lungs, but this does not affect your breathing if it is a small 

amount. If you swallow some metallic tin particles, they will leave your body in the feces. Very 

little tin can enter the body through unbroken skin. Your body can rid itself of most inorganic tin 

in weeks, but some can stay in your body for 2–3 months. Inorganic tin compounds leave your 

body very quickly; most are gone within a day. Very small amounts of tin stay in some tissues 

of your body, like the bones, for longer periods of time. 
TIN AND TIN COMPOUNDS 5 

1. PUBLIC HEALTH STATEMENT 

Further information on how tin enters and leaves your body is given in Chapter 3. 

1.5 HOW CAN TIN AND TIN COMPOUNDS AFFECT MY HEALTH? 

Scientists use many tests to protect the public from harmful effects of toxic chemicals and to find 

ways for treating persons who have been harmed. 

One way to learn whether a chemical will harm people is to determine how the body absorbs, 

uses, and releases the chemical. For some chemicals, animal testing may be necessary. Animal 

testing may also help identify health effects such as cancer or birth defects. Without laboratory 

animals, scientists would lose a basic method for getting information needed to make wise 

decisions that protect public health. Scientists have the responsibility to treat research animals 

with care and compassion. Scientists must comply with strict animal care guidelines because 

laws today protect the welfare of research animals. 

Because inorganic tin compounds usually enter and leave your body rapidly after you breathe or 

eat them, they do not usually cause harmful effects. However, humans who swallowed large 

amounts of inorganic tin in research studies suffered stomachaches, anemia, and liver and kidney 

problems. Studies with inorganic tin in animals have shown similar effects to those observed in 

humans. There is no evidence that inorganic tin compounds affect reproductive functions, 

produce birth defects, or cause genetic changes. Inorganic tin compounds are not known to 

cause cancer. 

Inhalation (breathing in), oral (eating or drinking), or dermal exposure (skin contact) to some 

organotin compounds has been shown to cause harmful effects in humans, but the main effect 

will depend on the particular organotin compound. There have been reports of skin and eye 

irritation, respiratory irritation, gastrointestinal effects, and neurological problems in humans 

exposed for a short period of time to high amounts of certain organotin compounds. Some 

neurological problems have persisted for years after the poisoning occurred. Lethal cases have 

been reported following ingestion of very high amounts. Studies in animals have shown that 

certain organotins mainly affect the immune system, but a different type primarily affects the 
TIN AND TIN COMPOUNDS 6 

1. PUBLIC HEALTH STATEMENT 

nervous system. Yet, there are some organotins that exhibit very low toxicity. Exposure of 

pregnant rats and mice to some organotin compounds has reduced fertility and caused stillbirth, 

but scientists still are not sure whether this occurs only with doses that are also toxic to the 

mother. Some animal studies also suggested that reproductive organs of males may be affected. 

There are no studies of cancer in humans exposed to organotin compounds. Studies of a few 

organotins in animals suggest that some organotin compounds can produce cancer. On the basis 

of no data in humans and questionable data from a study in rats, EPA has determined that one 

specific organotin, tributyltin oxide, is not classifiable as to human carcinogenicity; that is, it is 

not known whether or not it causes cancer in humans. 

More information on the health effects of tin in humans and animals is found in Chapter 3. 

1.6 HOW CAN TIN AND TIN COMPOUNDS AFFECT CHILDREN? 

This section discusses potential health effects in humans from exposures during the period from 

conception to maturity at 18 years of age. 

Children can be exposed to tin compounds (inorganic or organic) in the same manner as adults: 

through the diet or by contact with contaminated soil at or near hazardous waste sites where 

these compounds are found. Some children eat significant amounts of dirt (a behavior called 

pica), which may lead to increased exposure if the soil is contaminated. In addition, children can 

be exposed if family members work with tin compounds and bring home tin residues in their 

clothing or tools. 

There are no studies on health effects in children exposed to tin compounds. However, it is 

reasonable to assume that children would exhibit the same type of health effects observed in 

exposed adults. We do not know whether children are more susceptible to the effects of 

exposure to tin and tin compounds than adults. There are no reports of adverse developmental 

effects in humans exposed to tin or its compounds, or of inorganic tin in animals. Studies in 

animals have shown that organotin compounds can cross the placenta and reach the fetus. 

Exposure of rodents to some organotins during pregnancy has produced birth defects in the 
TIN AND TIN COMPOUNDS 7 

1. PUBLIC HEALTH STATEMENT 

newborn animals. The results of several studies suggest that this may occur only at high 

exposure levels that cause maternal toxicity, but further research is needed to clarify this issue. 

One study found that rats whose mothers were exposed to tributyltin during pregnancy showed 

altered performance in some neurological tests conducted when they were young adults. 

Another study, also with tributyltin, found that exposure during gestation, lactation, and postlactation affected some developmental landmarks in female rats. There are no reports of tin or 

tin compounds in human breast milk, and there is no direct evidence in animals of transfer of 

these compounds to the young through nursing. 

More information regarding children’s health and tin and related compounds can be found in 

Section 3.7. 

1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO TIN AND TIN 

COMPOUNDS? 

If your doctor finds that you have been exposed to substantial amounts of tin and tin compounds, 

ask whether your children might also have been exposed. Your doctor might need to ask your 

state health department to investigate. 

Children living near waste sites containing tin and tin compounds are likely to be exposed to 

higher than normal environmental levels of tin through breathing, touching soil, and eating 

contaminated soil. 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. Some toothpastes and other dental products contain stannous fluoride, a tin 

containing compound. Children should be watched carefully when using these products and 

should not swallow these products. 

Because tin is naturally found in the environment at low levels, we cannot avoid being exposed 

to it. The major route of exposure to tin is from eating or drinking canned products. Reducing 

the amount of canned products you eat or drink may reduce your exposure to tin. Since tin 

concentrations in food increase if food is stored in opened cans, you can reduce your exposure by 
TIN AND TIN COMPOUNDS 8 

1. PUBLIC HEALTH STATEMENT 

storing unused portions of canned foods in a separate container. You may be exposed to organic 

tin compounds by eating seafood from areas that may be contaminated with organic tin 

compounds or from contact with household products that contain organotin compounds 

(polyurethane, plastic polymers, and silicon-coated baking parchment paper). Reducing the 

amount of seafood that you eat from areas that may be contaminated with organic tin compounds 

and reducing contact with household products that contain organic tin compounds may reduce 

your exposure to organic tin compounds. If you are accidentally exposed to large amounts of tin 

or tin compounds, consult a physician immediately. 

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

EXPOSED TO TIN AND TIN COMPOUNDS? 

There are tests to measure tin and organotin compounds in your blood, urine, feces, and body 

tissues. Normally, small amounts of tin are found in the body because of the daily exposure to 

small amounts in the food. Therefore, the available tests cannot tell you when you were exposed 

or the exact amount of tin to which you were exposed, but can help determine if you were 

exposed to an amount of tin or tin compounds unusually high in the near past. This information 

can be used to locate the source of exposure. 

Tests for tin and related compounds are not routinely performed at a doctor’s office because they 

require special equipment, but the doctor can take samples and send them to a testing laboratory. 

Further information on how tin can be measured in exposed humans is presented in Chapter 7. 

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. The EPA, the Occupational Safety and Health 

Administration (OSHA), and the Food and Drug Administration (FDA) are some federal 

agencies that develop regulations for toxic substances. Recommendations provide valuable 
TIN AND TIN COMPOUNDS 9 

1. PUBLIC HEALTH STATEMENT 

guidelines to protect public health, but cannot be enforced by law. The Agency for Toxic 

Substances and Disease Registry (ATSDR) and the National Institute for Occupational Safety 

and Health (NIOSH) are two federal organizations that develop recommendations for toxic 

substances. 

Regulations and recommendations can be expressed as “not-to-exceed” levels, that is, levels of a 

toxic substance in air, water, soil, or food that do not exceed a critical value that is usually based 

on levels that affect animals; they are then adjusted to levels that will help protect humans. 

Sometimes these not-to-exceed levels differ among federal organizations because they used 

different exposure times (an 8-hour workday or a 24-hour day), different animal studies, or other 

factors. 

Recommendations and regulations are also updated periodically 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 tin and tin compounds include the 

following: 

Several government agencies and the Congress have acted to protect human health by regulating 

tin compounds. The EPA has limited the use of certain organotin compounds in paints. OSHA 

has established workplace exposure limits of 0.1 milligrams per cubic meter of air (mg/m3

) for 

organotin compounds and 2 mg/m3

 for inorganic tin compounds, except oxides. NIOSH 

recommends workplace exposure limits of 2 mg/m3 for inorganic tin compounds, except for tin 

oxides, and 0.1 mg/m3

 for organotins, except tricyclohexyltin hydroxide. NIOSH states that a 

concentration of tricyclohexyltin hydroxide of 25 mg/m3 should be considered as immediately 

dangerous to life or health. The FDA regulates the use of some organic tin compounds in 

coatings and plastic food packaging. The FDA also has set limits for the use of tin, as stannous 

chloride, as an additive for food. 

Additional information on governmental regulations and guidelines regarding tin and compounds 

is found in Chapter 8 and Table 8-1. 
 

 

 

 

TIN AND TIN COMPOUNDS 10 

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 that result 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 ToxProfilesTM CD-ROM by calling the toll-free information 

and technical assistance number at 1-888-42ATSDR (1-888-422-8737), by e-mail at 

atsdric@cdc.gov, or by writing to: 

Agency for Toxic Substances and Disease Registry 

 Division of Toxicology 

1600 Clifton Road NE 

 Mailstop F-32 

 Atlanta, GA 30333 

 Fax: 1-770-488-4178 

Organizations for-profit may request copies of final Toxicological 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/ 
TIN AND TIN COMPOUNDS 11 

2. RELEVANCE TO PUBLIC HEALTH 

2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO TIN AND TIN 

COMPOUNDS IN THE UNITED STATES 

Tin is a naturally occurring element. It is a silver-white, malleable, and somewhat ductile metal. The 

earth's crust contains about 2–3 ppm tin, comprising 0.0006% of the earth's crust. Major uses of tin 

include cans and containers, electrical, construction, and transportation. Industrially important tin 

compounds can be categorized as inorganic (those without a tin-carbon bond) and organic (those having a 

tin-carbon bond). Inorganic tin compounds are used in the glass industry, and also serve as the base for 

the formulation of colors, as catalysts, and in perfumes and soaps. The major commercial applications for 

organotin compounds are as polyvinyl chloride (PVC) heat stabilizers, biocides, catalysts, agrochemicals, 

and glass coatings. 

Tin may be released to the environment from natural and anthropogenic sources. Tin is a component of 

many soils and tin and inorganic tin compounds may be released by weathering and agricultural activities. 

Releases of tin to the environment may also occur from the production and use of tin and tin compounds. 

Tin is generally regarded as being relatively immobile in the environment. In general, organotin 

compounds are released to the environment through their production and use. Tributyltin and triphenyltin 

enter the environment directly from their use as antifouling paints and as pesticides. To a lesser extent, 

organotin compounds may also enter the environment by leaching from consumer products and from the 

disposal of products containing organotin compounds in landfills. Organotin compounds are generally 

found to partition to soils and sediments. 

Occupational exposure to tin may be significant in some industrial environments. Ambient 

environmental levels of tin are generally quite low, except in the vicinity of pollution sources. Human 

exposure to tin may occur by inhalation, ingestion, or dermal absorption. Dermal absorption is a 

significant route of occupational exposure for certain organotin compounds. The average daily tin intake 

of an adult in the United States was estimated at 4.003 mg (4 mg from food and 0.003 mg from air), and 

with undetectable levels contributed by drinking water. The most important source for exposure to tin is 

from food, especially canned food products. Tin-lined cans used to package food are the most important 

contributor to dietary tin intake. There was a significant correlation between the amount of canned food 

consumed and the concentration of tin in the diet. People eating a high percentage of their diet from 
TIN AND TIN COMPOUNDS 12 

2. RELEVANCE TO PUBLIC HEALTH 

canned foods will be exposed to higher amounts of tin than people eating more fresh foods. Tin 

concentrations in foods will depend on whether they are packaged in lacquer tin-lined cans or 

unlacquered cans. Mean tin concentrations ranging from <1 to 1,000 mg/kg have been found in foods 

packaged in unlacquered or partially lacquered cans, while the average tin concentration in foods in 

lacquered cans has been reported to be 0–6.9 mg/kg. More than 90% of tin-lined cans used for food today 

are lacquered. Only light colored fruit and fruit juices are packed in unlacquered cans, since tin helps 

maintain the color of the product. 

Data on human exposure to organotin compounds are more limited. Potential exposure for the general 

population to organotin compounds would be expected to exist for butyltin compounds, phenyltin 

compounds, and di- and monomethyltin, according to available monitoring data. In a market basket study 

in Japan, daily intakes of tributyltin and triphenyltin in Japan were estimated to be 6.9 and 5.4 μg, 

respectively, in 1991 and 6.7 and 1.3 μg, respectively, in 1992, with 95% of the daily intakes of tributyltin 

and triphenyltin coming from the fish, mollusks, and crustaceans food group. Mono- and dimethyltin and 

mono- and dibutyltin compounds have been detected in drinking water in Canada where PVC pipes, 

containing these organotin compounds, are used in the distribution of drinking water. It has been 

demonstrated that butyltin compounds in siliconized baking parchment can be transferred to food baked 

on this type of baking parchment. Organotin compounds were found in household dust in a United 

Kingdom study. Monitoring data were not found to indicate whether the general population is exposed to 

other organotin compounds, such as trimethyltin and triethyltin. 

2.2 SUMMARY OF HEALTH EFFECTS 

Most of the information on the health effects of inorganic and organic tin in humans comes from studies 

of individuals exposed at work, volunteers exposed to controlled amounts, and accidental or intentional 

exposures. Except for the studies in volunteers, exposure characterization in the reports on humans is 

generally lacking. Numerous studies have been conducted on the effects of tin and related compounds in 

a variety of animal species (primarily rodents) mostly following ingestion by the oral route. 

Humans chronically exposed to inorganic tin (e.g., stannic oxide dust or fumes) manifest a benign form of 

pneumoconiosis known as stannosis, which involves mainly the lower respiratory system. 

Gastrointestinal effects, such as nausea, vomiting, and diarrhea have been reported in subjects ingesting 

food items contaminated with inorganic tin. Based on the available studies in humans, there is no 
TIN AND TIN COMPOUNDS 13 

2. RELEVANCE TO PUBLIC HEALTH 

evidence that inorganic tin affects reproduction or development in humans or that it is a neurotoxin, 

immunotoxin, mutagenic, or carcinogenic agent in humans. A relatively limited number of studies in 

animals have not clearly established potential target organs for inorganic tin toxicity. Of the effects 

described, hematological signs of anemia and gastrointestinal distension appear to be best identified as 

tin-related. No adverse reproductive or developmental effects of inorganic tin were reported in a small 

number of studies available. Tin affects the metabolism of other metals such as copper, zinc, and iron; 

therefore, if the pharmacokinetics of these metals is altered, it is difficult to ascertain whether a specific 

effect is caused by exposure to tin itself or is due to fluctuations in tissue levels of other metals. 

Bioassays for carcinogenicity of inorganic tin have been negative. 

Cases of lethality have been reported after acute inhalation exposure to a mixture of vapors of trimethyltin 

and dimethyltin organotins and after acute oral ingestion of trimethyltin. In addition, approximately 

100 deaths occurred in France in 1954 following ingestion of a proprietary drug that seemed to have been 

contaminated with ethyltin triiodide, triethyltin iodide, or tetraethyltin. Deaths occurred after exposure to 

an estimate dose of 3 g triethyltin iodide over a period of 6–8 weeks. Those affected showed neurological 

signs and symptoms such as headache, photophobia, altered consciousness, and convulsions. These 

appeared about 4 days after intoxication and, in individuals who recovered, continuous headaches and 

weakness persisted for at least 4 years. Additional cases of accidental or intentional acute inhalation, oral, 

or dermal intoxication with trimethyltin or triphenyltin also have included adverse neurological effects 

that persisted for a long time (years in some cases) after the poisoning episode. Organotins also are 

known to be skin and eye irritants in humans. 

There are no studies that evaluated whether organotin compounds cause developmental or reproductive 

alterations in humans or cancer. Limited inhalation data from intermediate-duration studies in animals 

indicate that organotins can produce lung alterations, irritation of the respiratory airways, skin, and eyes, 

and liver and kidney effects. In contrast to the limited inhalation database, an extensive oral database 

indicates that trimethyltin and triethyltin compounds are primarily neurotoxic, whereas tributyltin, 

dibutyltin, and dioctyltin are essentially immunotoxic. Hepatic and hematological effects also have been 

described in animals treated orally with organotins. Triphenyltin, dibutyltin, and tributyltin, when 

administered during pregnancy, have induced developmental and reproductive effects in rodents. 

However, it remains unclear whether these effects occur only at doses that induce maternal toxicity. 

Studies of genotoxic activity of organotin compounds have given mixed results depending on the specific 

compound and test system. Dibutyltin acetate, triphenyltin hydroxide, and tributyltin oxide have been 

tested for carcinogenicity in long-term bioassays. The first two compounds produced no evidence of 
TIN AND TIN COMPOUNDS 14 

2. RELEVANCE TO PUBLIC HEALTH 

carcinogenicity in Fischer-344 rats and B6C3F1 mice, whereas the results for tributyltin oxide in Wistar 

rats were considered questionable by the EPA and led to a carcinogenic classification of “not classifiable 

as to human carcinogenicity” or, to a group of substances for which there is “inadequate information to 

assess carcinogenic potential,” according to updated guidelines. Additional studies with higher doses of 

triphenyltin hydroxide in Wistar rats and NMRI mice showed increased incidence of pituitary cancer in 

female rats and of liver cancer in female mice. 

A greater detailed discussion of immunological, neurological, reproductive/developmental, and 

hematological effects of tin and compounds follows. The reader is referred to Section 3.2, Discussion of 

Health Effects by Route of Exposure, for additional information on other health effects. 

Immunological and Lymphoreticular Effects. There are no studies that evaluated whether 

environmental concentrations of tin or organotin compounds alter immunocompetence in humans. 

However, acute exposure of rats to higher concentrations (generally >2 mg/kg/day) of tributyltins and 

other organotins have caused immune alterations. The effect is characterized by reduced thymus weight 

and size and lymphocyte depletion. Dialkyltins appear to directly interfere with proliferation of 

thymocytes, a cytostatic effect, whereas tributyltin oxide has a direct and selective toxic action on 

lymphocytes in the thymus. Long-term studies with tributyltin oxide in rats have demonstrated alterations 

in parameters of specific and nonspecific resistance at the relatively low dose level of 0.25 mg/kg/day. 

Although no adverse immunological effects have been described in humans exposed to tin and 

compounds, the high sensitivity exhibited by the rat thymus and the impairment in resistance to infection 

suggest that similar responses might occur in humans exposed to these chemicals at high concentrations 

or for long periods of time. 

Neurological Effects. While adverse neurological effects have been described in animals following 

oral exposure to various organotin compounds, triethyltins and trimethyltins are by far the most potent 

neurotoxins of the organotins and have been the most extensively studied in experimental animals. The 

results from animal studies have confirmed the findings reported in cases of accidental or intentional 

exposure to trimethyltin and triethyltin in humans. Triethyltin produces brain and spinal cord swelling, 

which is characterized by accumulation of fluid between myelin layers, splitting of the myelin sheets, and 

formation of intramyelin vacuoles. This was observed in fatal cases that occurred from a massive 

accidental intoxication episode in France in 1954 and similar results have been reproduced in animal 

studies exposed to doses t1 mg/kg/day. Individuals affected in the French case showed neurological 

signs and symptoms such as headache, photophobia, altered consciousness, and convulsions. These 
 

TIN AND TIN COMPOUNDS 15 

2. RELEVANCE TO PUBLIC HEALTH 

appeared about 4 days after intoxication and, in individuals who recovered, recurrent headaches and 

weakness persisted for at least 4 years. Studies in animals have confirmed the reversibility of some of the 

neurological effects. Trimethyltin produces neuronal necrosis, particularly in the hippocampus and other 

structures in the limbic system, and this has been demonstrated in humans and in animals. Studies in 

animals have described neuronal necrosis in the neocortex, pyriform cortex, hippocampal formation, basal 

ganglia, brain stem, spinal cord, and dorsal root ganglia after single doses of t1 mg/kg. The 

morphological changes that occur in the brain translate into behavioral alterations, such as aggression 

(both in humans and in animals), memory loss, and unresponsiveness. Some neurological symptoms can 

last for years. No population group has been identified that has undergone long-term exposure to low 

levels of trimethyltin or triethyltin, and no monitoring data are available to evaluate current exposures of 

the general population, but it is unlikely that adverse neurological effects would occur in humans exposed 

to environmental levels of organotins. 

Reproductive/Developmental Effects. There are no data regarding reproductive/developmental 

effects of inorganic or organic tin compounds in humans. Two early studies found no adverse 

reproductive/developmental effects of inorganic tin in rodents. Much of the information available 

regarding reproductive/developmental effects of organotins in animals comes from studies conducted in 

the 1990s. Numerous studies have been conducted with tributyltin, triphenyltin, and dibutyltin which 

have been shown to cause pregnancy failure, preimplantation loss, postimplantation loss, resorptions, and 

fetal death. The highest incidence of resorptions and postimplantation losses occurred when the 

chemicals were administered on gestation days 7–9. Doses that induced these effects were generally 

>3 mg/kg/day. Implantation loss has been attributed to a suppression of uterine decidualization caused by 

decreased levels of serum progesterone. Organotins have also proved to be embryotoxic and teratogenic, 

including in studies in vitro using cultured rat embryos. The most commonly seen malformation was cleft 

palate and other facial malformations. For dibutyltin dichloride, the highest incidence of malformations 

occurred when dosing on gestation day 8. A key issue in evaluating reproductive/developmental effects 

has been to ascertain whether the effects occur secondary to maternal toxicity or occur in the absence of 

maternal toxicity (generally assessed by clinical observations and alterations in body weight gain). Thus 

far, a conclusive answer has not been provided. Male rats exposed to 10 mg tributyltin/kg/day for 10 days 

had histologic alterations in the seminal vesicles and epididymis and reduced sperm counts, but except for 

these findings, reproductive effects of organotins in males have not been well studied. Two 

multigeneration studies in rats with tributyltin chloride showed slight alterations in developmental 

landmarks in male and female animals suggesting a possible endocrine modulatory role for this 

compound in laboratory rats. Results from studies in vitro show that some organotins can alter the 
 

TIN AND TIN COMPOUNDS 16 

2. RELEVANCE TO PUBLIC HEALTH 

activities of enzymes involved in the synthesis of sex hormones in mammals, which can alter the 

androgens/estrogens balance and affect sexual maturation. However, further studies are necessary to 

establish the relevancy of these findings to human exposures. 

Hematological Effects. No data were located regarding hematological effects of inorganic tin or 

organotins in humans. Tin affects the metabolism of a number of essential minerals such as iron, copper, 

zinc, calcium, and selenium by mechanisms that are not totally clear, but which could involve altered 

absorption and/or retention. Studies in animals have shown that excess dietary tin reduces serum iron and 

copper levels. Thus, as expected, feeding a diet with excess tin to rats produced signs of anemia, which 

was reversed by enriching the diet with iron and/or copper. It is reasonable to assume that individuals 

with low levels of iron or copper may be at risk of developing signs of anemia if at the same time they 

consume excessive amounts of tin. 

Organotin compounds have produced hematological effects in laboratory animals. In a 13-week study 

with dibutyltin dichloride in rats, the most sensitive end point was hemoglobin concentration which was 

depressed at a dose of 5.7 mg/kg/day, but not at 3.4 mg/kg/day. Long-term studies with tributyltin oxide 

in rats also have produced decreased hemoglobin concentrations. Since there was an indication of 

increased young erythrocytes and decreased serum iron concentrations, it was suggested that exposure to 

tributyltin oxide disrupts hemoglobin synthesis by interfering with iron uptake or by promoting iron loss. 

Exposure of rats to dioctyltin dichloride also reduced hemoglobin concentration in rats in a 6-week 

dietary study. Whether signs of anemia occur in humans exposed to environmental levels of organotin 

compounds is not known and, although plausible, this seems unlikely due to their relatively low 

environmental levels. 

2.3 MINIMAL RISK LEVELS 

Estimates of exposure levels posing minimal risk to humans (MRLs) have been made for tin and tin 

compounds. 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 
 

TIN AND TIN COMPOUNDS 17 

2. RELEVANCE TO PUBLIC HEALTH 

acute, intermediate, and chronic duration exposures for inhalation and oral routes. Appropriate 

methodology does not exist to develop MRLs for dermal exposure. 

Although methods have been established to derive these levels (Barnes and Dourson 1988; EPA 1990), 

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, or chronic 

bronchitis. As these kinds of health effects data become available and methods to assess levels of 

significant human exposure improve, these MRLs will be revised. 

Inhalation MRLs 

No inhalation MRLs were derived for inorganic tin or organic tin compounds since adequate experimental 

data were not available by this route of exposure. 

Oral MRLs 

Inorganic Tin. Acute oral data for inorganic tin were limited to an early reproductive/developmental 

study in rodents exposed during gestation (FDA 1972) and a study in which rats and mice were given 

either a single dose of stannous chloride or were treated for 14 days (NTP 1982). The NTP studies were 

pilot studies of limited scope designed primarily to establish dose levels to be tested in longer-term 

studies. Although the FDA (1972) study provided adequate information on embryotoxicity and 

teratogenicity of tin chloride, it is unknown whether sensitive end points for inorganic tin, such as 

hematological parameters, were affected in the dams because no evaluations were conducted. The 

intermediate-duration database is based on a limited number of studies, but a 13-week study in rats 

provided sufficient information for derivation of an intermediate oral MRL for tin (De Groot et al. 1973). 

No chronic-duration MRL was derived for inorganic tin because the lowest dose tested, 0.7 mg Sn/kg/day 

as stannous chloride, reduced survival in rats in a 42-month drinking water study (Schroeder et al. 1968). 

An MRL of 0.3 mg/kg/day has been derived for intermediate-duration oral exposure (15– 

364 days) to inorganic tin. 

The intermediate-duration MRL was based on a NOAEL of 32 mg Sn/kg/day (as stannous chloride) for 

hematological effects in Wistar rats fed the test material in the diet for 13 weeks (De Groot et al. 1973). 

x
TIN AND TIN COMPOUNDS 18 

2. RELEVANCE TO PUBLIC HEALTH 

The diet provided doses of approximately 0, 9.5, 32, 95, and 315 mg/kg/day. End points monitored 

included survival, body weight, food intake, hematology (hemoglobin, hematocrit, total erythrocytes, total 

and differential leukocytes), serum chemistry (transaminases, alkaline phosphatase, bilirubin), urinalysis, 

organ weights (nine organs), and gross and microscopic pathology. Tin in the standard diet was not 

determined, but the concentrations of calcium, phosphorus, iron, copper, and zinc were known. The 

highest dietary level tested caused reduced food consumption and abdominal distension on week 1. At 

week 8, loss of body weight occurred in males and females and one male died. At week 9, another three 

males died and the group was discontinued. Rats in the 95 mg/kg/day group showed poor appetite and 

abdominal distension the first 2 weeks; this was associated with decreased food consumption, but they 

continued growing. At termination, no significant differences in body weight were seen. Food 

consumption was also low in the 32 mg/kg/day group but only for week 1. Hemoglobin concentration 

was significantly reduced starting at week 4 in the 95 and 315 mg/kg/day groups (about 12 and 20%, 

respectively), and at week 4 in the 32 mg/kg/day males (3% reduction). Terminal hemoglobin and 

hematocrit were significantly reduced only in high-dose treated males (6 and 4%, respectively). Tin had 

no noticeable effect on osmotic resistance of the erythrocytes or on the number of reticulocytes. Serum 

alkaline phosphatase was significantly decreased at termination in both sexes, but there was no significant 

effect on transaminases or in bilirubin concentration. Terminal urine samples were unremarkable, as were 

relative organ weights. Rats from the high-dose group (315 mg/kg/day) that had to be terminated early 

showed distended intestines, slight edema of the pancreas, and grayish-brown livers. The high-dose rats 

had moderate testicular degeneration, severe pancreatic atrophy, spongy white matter in the brain, acute 

bronchopneumonia, enteritis, and liver changes characterized by homogeneous appearance of the liver 

cell cytoplasm and mild proliferation of the bile duct epithelium. In the 95 mg/kg/day group, treatmentrelated effects included bile duct epithelium proliferation and homogeneous cytoplasm at termination. 

Applying an uncertainty factor of 100 (10 for animal to human extrapolation and 10 for human 

variability) to the NOAEL of 32 mg/kg/day yields an intermediate-duration MRL of 0.3 mg/kg/day for 

inorganic tin. The 95 mg/kg/day dose level is considered a minimal LOAEL based on the unknown 

biological significance of a 12% reduction in hemoglobin concentration. 

Derivation of oral MRLs was considered for the following organotin compounds: tributyltin, triethyltin, 

trimetyltin, triphenyltin, dibutyltin, and dioctyltin. These are the organotins that have been subject to the 

most studies. Of these, relevant and adequate information was found only for tributyltin, for which an 

intermediate-duration MRL and a chronic-duration MRL were derived, and for dibutyltin, for which an 

intermediate-duration oral MRL was derived. 
19 

x

TIN AND TIN COMPOUNDS 

2. RELEVANCE TO PUBLIC HEALTH 

Dibutyltin. One of the lowest-observed-adverse-effect levels (LOAELs) for acute oral exposure to 

dibutyltin was 3.8 mg/kg/day for a reproductive effect in rats, a significant increase in postimplantation 

loss per litter, a serious LOAEL (Ema and Harazono 2000). The highest NOAEL below that LOAEL was 

2.5 mg/kg/day for developmental effects in rats (Ema et al. 1991b), which is very near the serious 

LOAEL. The chronic-duration database was limited to the NCI (1978a) study in which a relatively low 

dose, 6.7 mg/kg/day caused significant early mortality in rats. An intermediate-duration oral MRL was 

derived for dibutyltin dichloride. 

An MRL of 0.005 mg/kg/day has been derived for intermediate-duration oral exposure (15– 

364 days) to dibutyltin dichloride. 

The intermediate-duration oral MRL of 0.005 mg/kg/day for dibutyltin dichloride is based on a LOAEL 

of 5 mg/kg/day for immunological effects in rats (Seinen et al. 1977b). Groups of male weanling Wistar 

rats were fed diets containing 0, 50, or 150 ppm of the test material (>98% pure) for 4–6 weeks. Based 

on a body weight of 0.2 kg, it can be estimated that these levels provided doses of dibutyltin dichloride of 

approximately 0, 5, and 15 mg/kg/day (EPA 1988e). End points examined included body weight and 

parameters of humoral and cellular immune responses. The humoral immune response was assessed by 

measuring antibody formation against SRBC and E. coli lipopolysaccharide. The cellular immune 

response was assessed by examining allograft rejection. Final body weight after 4 weeks of exposure was 

not significantly altered relative to controls, but it was 28% lower than controls in the high-dose group 

after 6 weeks of exposure. Allograft rejection time was significantly delayed in the high-dose group 

relative to controls. In the tests for humoral response, the number of antibody-producing cells per million 

spleen cells was not affected, but the number per whole spleen was significantly decreased in a doserelated manner. This response was associated with a decreased hemagglutination titer in the high-dose 

group. The antibody titers against E. coli lipopolysaccharide were slightly but not significantly lower in 

treated groups than in controls. The dose of 5 mg/kg/day is the study LOAEL based on the reduction in 

hemagglutinating antibodies against SRBC. Applying an uncertainty factor of 1,000 (10 for animal to 

human extrapolation, 10 for use of a LOAEL, and 10 for species variability) to the LOAEL of 

5 mg/kg/day yields an intermediate-duration oral MRL of 0.005 mg/kg/day for dibutyltin dichloride. 

Dioctyltin. Only one acute-duration study was available that provided limited information on systemic 

effects and on effects on the immune system (Seinen et al. 1977a). Intermediate-duration studies focused 

mainly on the immune system and a relatively low dose tested, approximately 7 mg/kg/day, caused 

significantly mortality in guinea pigs after 4–5 weeks of treatment (Seinen et al. 1977b). No chronicduration studies were located. 
 

TIN AND TIN COMPOUNDS 20 

2. RELEVANCE TO PUBLIC HEALTH 

Triphenyltin. Most acute-duration studies provide information on reproductive and developmental 

effects and NOAELs and LOAELs are around 3–6 mg/kg/day. A dose level of 4.7 mg/kg/day was a 

serious reproductive LOAEL in rats (Ema et al. 1997b). An intermediate-duration study reported high 

lethality (100%) in rats at approximately 23 mg/kg/day, but did not report whether deaths occurred at 

lower dose levels tested (NCI 1978b). That study also reported that the lowest dose tested, approximately 

5 mg/kg/day, caused 25% reduction in body weight gain, a serious effect. High lethality was observed in 

rats in a chronic-duration study with the lowest dose level tested, 0.4 mg/kg/day (Tennekes et al. 1989b). 

A study in dogs, available in summary form only, found no significant effects of triphenyltin hydroxide 

on a wide range of end points at doses of up to 0.62 mg/kg/day in the diet for up to 52 weeks (Sachsse et 

al. 1987). 

Triethyltin. Most dose levels of triethyltin caused serious effects (primarily neurological) both in acute 

and intermediate duration oral studies. The highest NOAEL in an acute study was 2 mg/kg/day for 

neurological effects in a study by Snoeij et al. (1985), but that same dose level was a serious LOAEL for 

body weight in rats in that same study and caused ataxia and paralysis in a different study (Magee et al. 

1957). The highest intermediate LOAEL was 0.66 mg/kg/day for body weight in rats (Purves et al. 

1991), but 1.4 mg/kg/day was lethal to rats (Smith 1973) and 0.7–0.8 mg/kg/day were serious 

neurological LOAELs (Eto et al. 1971; Purves et al. 1991; Reiter et al. 1980). No chronic-duration 

studies were located. 

Trimethyltin. Most acute- and intermediate-duration studies of trimethyltin described serious 

neurological effects occurring at the lowest dose levels tested. The highest acute-duration NOAEL was 

0.7 mg/kg/day for neurological effects in rats (Snoeij et al. 1985), but 1 mg/kg/day was a serious 

neurological LOAEL (self-mutilating and aggressive behavior) in rats (Bouldin et al. 1981). Doses 

2 mg/kg/day were lethal (Brown et al. 1984; Nolan et al. 1990; Snoeij et al. 1985). In the few 

intermediate-duration studies available, the lowest LOAEL was 0.05 mg/kg/day for impaired performance 

of rat pups in a learning task, but there was no dose-response relationship (Noland et al. 1982). No 

chronic-duration studies were located. 

Tributyltin. The lowest LOAEL in acute-duration studies was 1 mg/kg/day and caused hyperactivity and 

dysfunction of spatial learning performance in adult rats whose mothers were exposed during pregnancy; 

no other dose levels were tested (Gardlung et al. 1991). This developmental effect is considered serious, 

which precludes its use for MRL derivation. The highest NOAEL below this LOAEL is 0.25 mg/kg/day 
21 

x

TIN AND TIN COMPOUNDS 

2. RELEVANCE TO PUBLIC HEALTH 

for reduction in maternal serum thyroxine levels in a developmental study in rats (Adeeko et al. 2003). 

Since no other maternal end points were monitored in the study, it seems inappropriate to use this 

NOAEL as basis for an acute oral MRL for tributyltin. Another relatively low dose, 2.5 mg/kg/day for 

6 days, caused significant weight loss in rats, a serious effect (Yallapragada et al. 1991). Intermediateand chronic-duration oral MRLs were derived for tributyltin. 

An MRL of 0.0003 mg/kg/day has been derived for intermediate-duration oral exposure (15– 

364 days) to tributyltin oxide. 

The intermediate-duration oral MRL of 0.0003 mg/kg/day for tributyltin oxide is based on a NOAEL of 

0.025 mg/kg/day for immunological effects in rats (Vos et al. 1990). Groups of male Wistar rats were fed 

a diet containing 0, 0.5, 5, or 50 ppm tributyltin oxide (95.3% pure) for 4.5–6 months. This diet provided 

approximately 0, 0.025, 0.25, and 2.5 mg/kg/day of the test material. Parameters of specific resistance 

evaluated included immunoglobulin M (IgM) and immunoglobulin G (IgG) response to ovalbumin and 

delayed-type hypersensitivity (DTH) response to ovalbumin and tuberculin after 6 months of treatment; 

resistance to Trichinella spiralis infection after 5.5 months; mitogenic response of thymus and spleen 

cells after 4.5 months; and surface marker analysis of mesenteric lymph nodes after 6 months. Parameters 

of nonspecific resistance examined included clearance of Listeria monocytogenes from the spleen after 

injection at 5 months and natural cell-mediated cytotoxicity of spleen and peritoneal cells after 

4.5 months. Neither body weight nor spleen weight were significantly altered after 4.5 months of 

treatment, but thymus weight was reduced by 17% relative to controls in the high-dose group. Neither the 

IgM nor IgG response to ovalbumin and T. spiralis was altered after 5.5 months of exposure. The 

immunoglobulin E (IgE) responses to T. spiralis, as determined by the passive cutaneous anaphylaxis 

reaction, was suppressed in a dose-related manner (significant in the mid- and high-dose groups). The 

DTH reactions to ovalbumin and tuberculin were not significantly altered after 6 months of dosing. There 

was an increase in the number of larvae T. spiralis in muscle after infection in the mid- and high-dose 

groups after 5.5 months of exposure to the test material. No significant effect was observed on the 

response of spleen cells to T- and B-mitogens after 4.5 months. The cell surface marker analysis of 

mesenteric lymph node cells showed a reduction in the relative count of T-lymphocytes and an increase in 

the percentage of B-lymphocytes in the mid- and high-dose groups after 6 months of treatment. The in 

vivo clearance of L. monocytogenes was impaired in the high-dose group after 5 months of treatment. 

Treatment with tributyltin oxide did induce a consistent effect on the natural killer cell activity of spleen 

and peritoneal cells after 4.5 months of exposure (decreased with low dose, increased with mid dose, and 

decreased with high dose). Based on the depression of IgE titers and increased T. spiralis in muscle after 

5.5 months of exposure to tributyltin oxide, the study LOAEL is 0.25 mg/kg/day and the NOAEL is 
22 

x

TIN AND TIN COMPOUNDS 

2. RELEVANCE TO PUBLIC HEALTH 

0.025 mg/kg/day. Applying an uncertainty factor of 100 (10 for animal to human extrapolation and 10 for 

intraspecies variability) to the NOAEL yields an intermediate-duration oral MRL of 0.0003 mg/kg/day. 

An MRL of 0.0003 mg/kg/day has been derived for chronic-duration oral exposure (365 days or 

more) to tributyltin oxide. 

The chronic-duration oral MRL of 0.0003 mg/kg/day for tributyltin oxide is based on a NOAEL of 

0.025 mg/kg/day for immunological effects in rats (Vos et al. 1990). Groups of male Wistar rats were fed 

a diet containing 0, 0.5, 5, or 50 ppm tributyltin oxide (95.3% pure) for 18 months. This diet provided 

approximately 0, 0.025, 0.25, and 2.5 mg/kg/day of the test material. Parameters of specific resistance 

evaluated included IgM and IgG response to sheep red blood cells (SRBC) after 16 months; IgM and IgG 

response to ovalbumin and DTH response to ovalbumin and tuberculin after 15 months of treatment; 

resistance to T. spiralis infection after 16.5 months; mitogenic response of thymus and spleen cells after 

16.5 months; and surface marker analysis of mesenteric lymph nodes after 18 months. Parameters of 

nonspecific resistance examined included clearance of L. monocytogenes from the spleen after injection at 

17 months and natural cell-mediated cytotoxicity of spleen and peritoneal cells after 16 months. No 

information was provided regarding body weight or weigh of the thymus and spleen weights at 

termination. Exposure to tributyltin oxide did not affect the primary IgM or the secondary response to 

SRBC after 16 months of dosing. Neither the IgM nor IgG response to ovalbumin and T. spiralis were 

altered after 15 months of exposure, but the IgE responses to T. spiralis, as determined by the passive 

cutaneous anaphylaxis reaction, were suppressed in a dose-related manner (significant in the mid- and 

high-dose groups). The DTH reactions to ovalbumin and tuberculin were not significantly altered after 

16 months of dosing. There was an increase in the number of larvae T. spiralis in muscle after infection 

in the mid- and high-dose groups after 16.5 months of exposure to the test material. No significant effect 

was observed on the response of spleen cells to T- and B-mitogens after 16 months. The cell surface 

marker analysis of mesenteric lymph node cells showed a reduction in the relative count of 

T-lymphocytes and an increase in the percentage of B-lymphocytes in the mid- and high-dose groups 

after 18 months of treatment. The in vivo clearance of L. monocytogenes was impaired in the high-dose 

group after 17 months of treatment. Treatment with tributyltin oxide for 16 months significantly reduced 

the natural killer cell activity of spleen and peritoneal cells, but there was no clear dose-response 

relationship. Based on the depression of IgE titers and increased T. spiralis in muscle after 16.5 months 

of exposure to tributyltin oxide, the study LOAEL is 0.25 mg/kg/day and the NOAEL is 

0.025 mg/kg/day. Applying an uncertainty factor of 100 (10 for animal to human extrapolation and 10 for 

intraspecies variability) to the NOAEL yields a chronic-duration oral MRL of 0.0003 mg/kg/day. 
TIN AND TIN COMPOUNDS 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 ton and tin 

compounds. 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. 

Because there is such a large number of inorganic tin and organotin compounds, only the most widely 

studied compounds and those that present the greatest potential for human exposure have been selected 

for the discussion of health effects. In addition to primary studies, review articles and government reports 

are occasionally provided in order to assist the reader in understanding more fully the toxicology of the 

tin compounds. 

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 and illustrated in 

figures. The points in the figures showing no-observed-adverse-effect levels (NOAELs) or lowestobserved-adverse-effect levels (LOAELs) reflect the actual doses (levels of exposure) used in the studies. 

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 
TIN AND TIN COMPOUNDS 24 

3. HEALTH EFFECTS 

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 and 

figures 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. 

Levels of exposure associated with carcinogenic effects (Cancer Effect Levels, CELs) of tin compounds 

are indicated in Table 3-5 and Figure 3-5. 

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 

Little information has been published regarding the effects of inhaled inorganic tin or organotin 

compounds on human health. Reports of human occupational exposures often involve multiple chemicals 

and lack details on actual exposure concentrations and conditions. Some reports of humans must also be 

regarded as anecdotal. The older animal literature (from the 1950s) includes inhalation studies that are 

lacking in description of methods and in reporting of experimental findings. However, it is still possible 

to characterize some aspects of tin toxicity due to inhalation of inorganic tin and organotin compounds. 

Exposure levels of the inhaled organotin compounds are expressed as milligrams per cubic meter (mg/m3

) 

of the specific tin compound unless otherwise noted. Doses are not expressed as doses of tin due to the 
TIN AND TIN COMPOUNDS 25 

3. HEALTH EFFECTS 

covalent bond between the tin and the organic moiety. There are no data for specific inorganic tin 

compounds. Calculations of parts per million (ppm) values are included where appropriate. Table 3-1 

and Figure 3-1 summarize available quantitative information on health effects that have been observed in 

animals after inhalation exposure to tributyltins. Exposure levels are expressed as ppm in Table 3-1 and 

Figure 3-1. A table and figure are not presented for inorganic tin compounds due to limitations of the 

available studies. 

3.2.1.1 Death 

Inorganic Tin Compounds. No studies were located regarding lethality in humans or animals after 

inhalation exposure to inorganic tin compounds. 

Organotin Compounds. Deaths have been reported in humans following exposure to organotins. One of 

six workers died 12 days following exposure to a mixture of half dimethyltin and half trimethyltin 

chloride vapor that occurred during the cleaning of a caldron at a chemical plant. Maximum exposure 

was a total of 1.5 hours over a 3-day working period (Rey et al. 1984). No estimates of exposure levels 

were given. The symptoms preceding death included excretion of high levels of tin in the urine, 

respiratory depression, and coma. More uncertain is the report of a female worker who died following a 

drenching with triphenyltin chloride, diphenyltin dichloride, and other unidentified compounds. No 

estimates of exposure levels were given. Death was apparently caused by renal failure 12 days after 

exposure (NIOSH 1976). No other studies were located regarding lethality in humans after inhalation 

exposure to organotin compounds. 

A 4-hour LC50 of 77 mg/m3

 for tributyltin oxide (as total particles) was described by Schweinfurth and 

Gunzel (1987) in a summary of acute studies; the LC50 for particles with a diameter of <10 μm was 

65 mg/m3

. The summary also indicates that a concentration of 20 mg/m3 of an aerosol of tributyltin oxide 

was lethal to guinea pigs within 1 hour of exposure. Lethality in mice was observed following single or 

repeated daily exposures to a butyltin mixture (81.2% tributyltin bromide and 3.7% dibutyltin dibromide) 

together with other unidentified compounds (15.1%) (Igarashi 1959). The concentration was 5.65 mg 

tin/m3

 (1.16 ppm) as the butyltin mixture for different durations of exposure. The tributyltin bromide 

concentration was 1.1 ppm and that for dibutyltin bromide was 0.06 ppm. For a 2-day, 8-hour/day 

exposure, approximately 80–90% of the exposed mice died. Despite the observation of other signs of 

toxicity (see Section 3.2.1.2) the exposure of the mice to multiple compounds confound the interpretation 

of the data. 
249

0.42

0.42

0.42

250

0.39

251

0.3

0.3

0.3

252

0.39

0.39

0.39

0.39

0.39

26 

Table 3-1 Levels of Significant Exposure to Tributyltins - Inhalation 

Exposure/ LOAEL 

Duration/ a Key to 

Figure 

Species 

(Strain) 

Frequency 

(Route) 

ACUTE EXPOSURE 

Systemic 

1 Mouse 

(NS) 

6 d 

7 hr/d 

System 

Cardio 

NOAEL 

(ppm) 

0.42 

Less Serious 

(ppm) 

Serious 

(ppm) 

Reference 

Chemical Form 

Igarashi 1959 

TBT 

Hepatic 0.42 (blood congestion) 

Renal 0.42 (glomerular swelling, 

tubular epithelial lesions) 

Reproductive 

2 Rat 

(NS) 

10 d 

5 hr/d 0.39 (40% decrease in 

reproduction) 

Iwamoto 1960 

TBT 

INTERMEDIATE EXPOSURE 

Systemic 

3 Rat 

(NS) 

95 d 

6 hr/d Resp 0.3 (lung hyperemia, 

catarrhal bronchitis) 

Gohlke et al 1969 

TBT 

Hepatic 0.3 (minor fatty 

degeneration) 

Ocular 0.3 (inflamed eyes, nostrils) 

4 Rat 

(NS) 

80 d Resp 0.39 (bronchitis edema) Iwamoto 1960 

TBT 

Cardio 0.39 (myocardial atrophy) 

Hepatic 0.39 (atrophy, necrosis) 

Renal 0.39 (swelling and congestion) 

Other 0.39 (splenic hyperplasia, 

thickened sheaths) 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
253

0.39

27 

Table 3-1 Levels of Significant Exposure to Tributyltins - Inhalation (continued) 

a Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

NOAEL 

(ppm) 

Less Serious 

(ppm) 

LOAEL 

Serious 

(ppm) 

Reference 

Chemical Form 

Reproductive 

5 Rat 

(NS) 

80 d 0.39 Iwamoto 1960 

TBT 

a The number corresponds to entries in Figure 3-1. 

Cardio = cardiovascular; d = day(s); Derm = dermal; hr = hour(s); LC50 = lethal concentration, 50% kill; LOAEL = lowest-observed-adverse-effect level; NOAEL = 

no-observed-adverse-effect level; Resp = respiratory 

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TIN AND TIN COMPOUNDS 30 

3. HEALTH EFFECTS 

In rats exposed nose-only for 29–32 days for 4 hours to doses of 0, 0.03 (vapor), 0.16 (vapor), or 

2.8 (aerosol) mg/m3

 of tributyltin oxide 5 days/week for 21–24 treatments, the mortality in the high-dose 

group was 5/10 males and 6/10 females (Schweinfurth and Gunzel 1987); no toxicity was noticed in the 

groups exposed to vapors. Little detail was presented in this brief summary. 

3.2.1.2 Systemic Effects 

No studies were located regarding cardiovascular, hematological, or musculoskeletal effects in humans or 

animals after inhalation exposure to inorganic tin or organotin compounds. 

The highest NOAEL values and all reliable LOAEL values for systemic effects in each species and 

duration category are recorded in Table 3-1 and plotted in Figure 3-1. 

Respiratory Effects. 

Inorganic Tin Compounds. Stannic oxide dust or fumes produce a benign form of pneumoconiosis, 

known as stannosis, in humans (Cutter et al. 1949; Dundon and Hughes 1950; Pendergrass and Pryde 

1948). The workers exhibiting this pulmonary condition had industrial exposures ranging from 15 to 

20 years. No exposure levels were included in the case reports. In all cases, chest x-rays of the workers 

showed discrete opaque shadows throughout the lungs, attributed to stannic oxide deposits. However, 

there was no impairment of pulmonary function or systemic disease. It also has been reported that x-rays 

of tin foundry workers confirmed more than 150 cases of stannosis by 1959 (Stewart and Lassiter 2001). 

No studies were located regarding respiratory effects in animals after inhalation exposure to inorganic tin 

compounds. 

Organotin Compounds. Respiratory depression requiring artificial ventilation occurred in three of six 

chemical workers. The exposure duration was a total of 1.5 hours over a 3-day working-period to a 

mixture containing half dimethyltin and half trimethyltin chloride (Rey et al. 1984). Although the two 

surviving workers, who were the most severely affected, developed permanent neurological disabilities, 

respiratory problems did not persist. 
 

TIN AND TIN COMPOUNDS 31 

3. HEALTH EFFECTS 

Tributyltin oxide has been implicated in producing irritation of the upper respiratory tract and chest 

irritation, tightness, and pain in workers using a rubber material containing tributyltin oxide. Exposure 

conditions were not described. No changes were observed in pulmonary function tests (NIOSH 1976). 

Wax and Dockstader (1995) reported that all members of a family of five (two adults and three children) 

complained of sore throat, burning nose, and wheezing 24 hours after a room in their home had been 

painted with a paint containing tributyltin oxide for mildew control. Cough and difficulty in breathing, 

characterized by inspiratory discomfort, were observed in a man a few hours after inhaling an unspecified 

amount of powdered trimethyltin chloride (Saary and House 2002). Shortness of breath and chest 

discomfort was still present 20 days after the exposure. 

Inflammatory changes consisting of hyperemia and bronchitis were observed in the respiratory system of 

rabbits exposed to 4–6 mg/m3

 (0.30–0.45 ppm) tributyltin chloride for 95 days (Gohlke et al. 1969). 

Histopathology, consisting of severe bronchitis and vascular and alveolar edema, was seen in rats exposed 

to 2 mg tin/m3

 (0.41 ppm) as a mixture of tributyltin bromide (0.39 ppm), dibutyltin dibromide 

(0.02 ppm), and hydrocarbon impurities for 80 days (Iwamoto 1960). Since these were terminal 

histopathological evaluations only, it is not known whether the changes were reversible or would have 

produced functional impairment in the animals if exposure had continued. 

Information summarized by Schweinfurth and Gunzel (1987) indicate that a single 4-hour exposure of 

rats to aerosols of tributyltin oxide produced signs of irritation such as nasal discharge, lung edema and 

congestion. 

Gastrointestinal Effects. 

Inorganic Tin Compounds. No studies were located regarding gastrointestinal effects in humans or in 

animals after inhalation exposure to inorganic tin compounds. 

Organotin Compounds. Very limited information is available in humans. Wax and Dockstader (1995) 

reported that nausea and vomiting occurred among all the members of a family of five who were exposed 

at home to tributyltin oxide contained in paint for mildew control. Saary and House (2002) reported that 

a man who inhaled powdered trimethyltin chloride complained of substernal and epigastric burning with 

flatulence a few hours after exposure. The abdominal pain still persisted 2 months after exposure. 
 

TIN AND TIN COMPOUNDS 32 

3. HEALTH EFFECTS 

Hematological Effects. 

Inorganic Tin Compounds. No studies were located regarding hepatic effects in humans or in animals 

after inhalation exposure to inorganic tin compounds. 

Organotin Compounds. Data concerning hepatic effects of organotins in humans and animals are 

limited. 

Autopsy of a chemical worker who died following exposure to a combination of methyltin salts (see 

Section 3.2.1.1) revealed massive fatty degeneration of liver cells and necrosis (Rey et al. 1984). 

Fatty degeneration was observed at necropsy in animals killed after a 95-day exposure period to 4– 

6 mg/m3

 (0.30–0.45 ppm) tributyltin chloride (Gohlke et al. 1969). Histopathology, consisting of atrophy 

and slight necrosis of the liver, was seen in rats exposed to 2 mg tin/m3

 (0.41 ppm) as a mixture of 

tributyltin bromide (0.39 ppm), dibutyltin dibromide (0.02 ppm), and hydrocarbon impurities for up to 

80 days as part of a study of reproductive function (Iwamoto 1960). Atrophy of the liver cells increased 

with exposure duration in the females. Some recovery was apparent if exposure to tin was stopped prior 

to sacrifice. The longer the duration of exposure, the less complete the recovery. 

Renal Effects. 

Inorganic Tin Compounds. No studies were located regarding renal effects in humans and animals after 

inhalation exposure to inorganic tin compounds. 

Organotin Compounds. Data concerning renal effects of organotins in humans and animals are limited. 

Autopsy of the one chemical worker who died following exposure to the combination of the methyltin 

salts (see Section 3.2.1.1) revealed shock kidneys (i.e., proximal tubule degeneration), which represents 

serious tubule damage (Rey et al. 1984). The other five exposed men had high tin concentrations in the 

urine with the highest levels occurring in the most severely affected. 

Inhalation exposure of mice to a concentration of 5.65 mg tin/m3

 (1.16 ppm) as a mixture of tributyltin 

bromide (1.1 ppm), dibutyltin dibromide (0.06 ppm), and hydrocarbon impurities for 7 hours/day over 

6 days produced pathological changes in the kidney (Igarashi 1959). Necropsy of animals revealed slight 
 

TIN AND TIN COMPOUNDS 33 

3. HEALTH EFFECTS 

degenerative changes in the glomeruli, convoluted tubules, and collecting tubules as well as extramedullary hematopoiesis. More extensive kidney pathology was observed in rats exposed to 2 mg tin/m3 

(0.41 ppm) as a mixture of tributyltin bromide (0.39 ppm) and dibutyltin dibromide (0.02 ppm) for 

2 hours/day for 80 days. Kidney damage consisted of extensive congestion and swelling of the renal 

tubular epithelium (Iwamoto 1960). 

Dermal Effects. 

Inorganic Tin Compounds. Contact with inorganic tin salts produces mild irritation of the skin and 

mucous membranes (WHO 1980). However, no specific studies were located regarding dermal effects in 

humans and animals after inhalation exposure to inorganic tin compounds. 

Organotin Compounds. No studies were located regarding dermal effects in humans after inhalation 

exposure to organotin compounds. Occupational exposure produces such effects as discussed in 

Section 3.2.3.1. 

Dermal effects were observed during inhalation studies in mice that were exposed to a butyltin mixture 

(30 parts tributyltin bromide to 1 part dibutyltin dibromide) and consisted of reddening of the skin and 

dilatation of the blood vessels of the nose, feet, and tail (Igarashi 1959). These effects may have been 

caused by direct contact with the chemical. 

Ocular Effects. 

Inorganic Tin Compounds. No information was located regarding ocular effects in humans following 

exposure to inorganic tin compounds. 

Organotin Compounds. Inflamed eyes and nasal mucous membranes were observed in the last month of 

a 95-day inhalation study of tributyltin chloride in female rats (Gohlke et al. 1969). The animals were 

exposed to concentrations of 4–6 mg/m3

 (0.30–0.45 ppm) for 6 hours/day, 5 days/week. 
 

TIN AND TIN COMPOUNDS 34 

3. HEALTH EFFECTS 

3.2.1.3 Immunological and Lymphoreticular Effects 

No studies were located regarding immunological effects in humans or animals after inhalation exposure 

to inorganic tin or organotin compounds. However, some lymph node atrophy was observed in rats 

exposed to a butyltin mixture for 14 days (Iwamoto 1960). 

3.2.1.4 Neurological Effects 

Inorganic Tin Compounds. No studies were located regarding neurological effects in humans or in 

animals after inhalation exposure to inorganic tin compounds. 

Organotin Compounds. A study by Rey et al. (1984) provides some information on neurobehavioral 

changes in humans after exposure to organotin compounds (dimethyltin dichloride and trimethyltin 

chloride). The study describes the cases of six chemical workers exposed to methyltins primarily by 

inhalation who experienced headache, tinnitus, deafness, impaired memory, disorientation, 

aggressiveness, psychotic and other severe neuropsychiatric behavior, syncope, and loss of consciousness 

as symptoms of exposure; one subject died. The two surviving workers with the highest urinary tin levels 

exhibited fixed neurological effects which were not resolved more than 6 years after exposure. The 

remaining three survivors returned to work, but had memory loss, which persisted for 6 months. Similar 

cases have been reported by other investigators. Fortemps et al. (1978) reported that two chemists who 

had been intermittently exposed to vapors of dimethyltin dichloride and trimethyltin chloride for about 

3 months abruptly developed a status of mental confusion with generalized epileptic seizures. Before the 

acute episode, the subjects had complained of headaches, pain in various organs, and psychological 

disturbances such as memory defects, vigilance loss, insomnia, anorexia, and disorientation. Both 

patients recovered completely following removal from exposure. Ross et al. (1981) examined 22 male 

workers 1 month following exposure to trimethyltin spillage (presumable inhalation and dermal exposure 

occurred) and compared the frequency of neurological symptoms between those who suffered high 

exposure with those with lower exposure. Those highly exposed showed a significantly higher incidence 

of nonspecific symptoms such as forgetfulness, fatigue and weakness, loss of motivation, and specific 

symptoms such as bouts of depression and attacks of rage and temper compared to those with lower 

exposure. Some symptoms persisted for at least 3 years following the accident. Yanofsky et al. (1991) 

and Feldman et al. (1993) described the case of a 23-year-old male who was accidentally exposed to 

vapors of a trimethyltin compound and 72 hours later exhibited delirium, spatial disorientation, 

perseveration, inappropriate affect, and memory loss. Urine and serum assays for tin showed 
 

TIN AND TIN COMPOUNDS 35 

3. HEALTH EFFECTS 

considerably elevated concentrations of trimethyltin when tested 3 weeks following the accident. Five 

months after the accident, the man experienced complex partial seizures that required him to take 

anticonvulsant medication for 7 years. Four years after exposure, tests revealed persistent memory 

defects, cognitive dysfunction, and dysphoria. Saary and House (2002) described the case of a man who 

worked in a chemistry laboratory and inhaled an undetermined amount of powdered trimethyltin chloride 

on a single occasion. Within 3 hours of exposure he felt agitated and he later developed a headache, 

dizziness, and twitching of the right eye and cheek. Two months after exposure, he continued 

experiencing twitching of his eyelids and arms and complained of suffering short-term memory problems 

and difficulty retaining new information. 

No relevant studies were located regarding neurological effects in animals after inhalation exposure to 

organotin compounds. It was reported that no histopathological changes were observed in the brains of 

mice following a 6-day inhalation exposure to 2.12 mg tin/m3

 (0.44 ppm) as a mixture of tributyltin 

bromide (0.42 ppm), dibutyltin dibromide (0.02 ppm), and hydrocarbon impurities (Igarashi 1959). 

3.2.1.5 Reproductive Effects 

Inorganic Tin Compounds. No studies were located regarding reproductive effects in humans or animals 

after inhalation exposure to inorganic tin compounds. 

Organotin Compounds. No studies were located regarding reproductive effects in humans after 

inhalation exposure to organotin compounds. 

A study in rats was conducted to assess reproductive effects of a mixture of tributyltin bromide (81.2%) 

with other compounds such as dibutyltin dibromide (Iwamoto 1960). The rats were exposed to 2 mg 

tin/m3

 (0.41 ppm) for acute- and intermediate-duration exposures (equivalent to 0.39 ppm tributyltin 

bromide and 0.02 ppm dibutyltin dibromide). Pregnancy rates were markedly reduced after 4 weeks to 

3 months of exposure, but returned to near control rates when exposure was discontinued. Histopathological evaluations were made in separate studies of different exposure durations (14–80 days) 

followed by recovery periods. No changes were seen in males, but atrophy of the glandular uterus was 

observed as early as 14 days of exposure in females. All effects were reversed during the recovery 

period. Although a mixture of butyltin compounds was used and the results were not clearly reported, 

this study suggests that some impairment of female reproductive functions may occur after inhalation of 

these compounds. 
TIN AND TIN COMPOUNDS 36 

3. HEALTH EFFECTS 

3.2.1.6 Developmental Effects 

No studies were located regarding developmental effects in humans or animals after inhalation exposure 

to inorganic tin or organotin compounds. 

3.2.1.7 Cancer 

No studies were located regarding cancer effects in humans and animals after inhalation exposure to 

inorganic tin or organotin compounds. 

3.2.2 Oral Exposure 

In contrast to the limited information on the inhalation toxicity of tin compounds (Section 3.2.1), there are 

considerable more data regarding the effects of oral exposure to organotin compounds, particularly in 

animal studies. Although there is less information concerning health effects produced by oral exposure to 

inorganic tin compounds, the data from animal studies allow some characterization of health effects of 

these compounds. Dosages are expressed as milligrams of tin per kilogram of body weight per day (mg 

tin/kg/day) as the specific inorganic tin compound fed or administered orally. Table 3-2 and Figure 3-2 

summarize available quantitative information on health effects that have been observed in animals after 

oral exposure to inorganic tin compounds. Similar information for organotin compounds is given in 

Tables 3-3 through 3-8 and Figures 3-3 through 3-8. In order to be consistent with most studies in the 

literature, dosages are expressed as mg/kg/day of the specific organotin compound rather than as a tin 

equivalent. 

3.2.2.1 Death 

Inorganic Tin Compounds. No studies were located regarding lethality in humans after oral ingestion of 

inorganic tin compounds. 

In animals, the lowest oral dose that produced deaths in rats following a single gavage administration was 

473 mg/kg body weight stannous chloride (NTP 1982). However, all rats survived doses up to 

945 mg/kg/day when the compound was fed in the diet for 14 days (NTP 1982). For mice, the lowest oral 
93

473

95

378

96

1229

2252

31

2248

31

2255

31

37 

Table 3-2 Levels of Significant Exposure to Inorganic Tin - Oral 

a Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) 

ACUTE EXPOSURE 

Death 

1 Rat 

(Fischer- 344) 

once 

(GW) 

System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

473 F (1/5 females died on day 

3) 

Reference 

Chemical Form 

NTP 1982 

SnCl2 

2 Mouse 

(B6C3F1) 

once 

(GW) 378 (1/5 males and 1/5 

females

 died on day 3) 

NTP 1982 

SnCl2 

Systemic 

3 Mouse 

(B6C3F1) 

14 d 

7 d/wk 

(F) 

1229 (males and females 

gained less weight than 

those in the lowest dose 

group) 

NTP 1982 

SnCl2 

Reproductive 

4 Rat 

(Wistar) 

10 d 

Gd 6-15 

1 x/d 

(GW) 

31 F FDRL 1972 

SnCl2 

5 Mouse 

(CD-1) 

10 d 

Gd 6-15 

1 x/d 

(GW) 

31 F FDRL 1972 

SnCl2 

6 Hamster 

(Golden 

Syrian) 

5 d 

Gd 6-10 

1 x/d 

(GW) 

31 F FDRL 1972 

SnCl2 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
2253

31

2249

31

2256

31

97

315

100

325

98

325

33

98

325

33

98

38 

Table 3-2 Levels of Significant Exposure to Inorganic Tin - Oral (continued) 

a Key to 

Figure 

Species 

(Strain) System 

Exposure/ 

Duration/ 

Frequency 

(Route) 

LOAEL 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

Serious 

(mg/kg/day) 

Reference 

Chemical Form 

Developmental 

7 Rat 

(Wistar) 

10 d 

Gd 6-15 

1 x/d 

(GW) 

31 FDRL 1972 

SnCl2 

8 Mouse 

(CD-1) 

10 d 

Gd 6-15 

1 x/d 

(GW) 

31 FDRL 1972 

SnCl2 

9 Hamster 

(Golden 

Syrian) 

5 d 

Gd 6-10 

1 x/d 

(GW) 

INTERMEDIATE EXPOSURE 

Death 

10 Rat 

(Wistar) 

13 wk 

7 d/wk 

(F) 

Systemic 

11 Cardio Rat 

(Wistar) 

4 wk 

7 d/wk 

(F) 

31 

315 (4/10 males died) 

325 

FDRL 1972 

SnCl2 

DeGroot et al. 1973 

SnCl2 

DeGroot et al. 1973 

Sn3(PO4)2 

Gastro 98 325 (slightly distended small 

and large intestine) 

Hemato 33 98 (decreased hemoglobin 

and hematocrit) 

Renal 

Bd Wt 

325 

33 98 (30% decreased body 

weight gain in males) 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
101

440

440

440

440

440

104

315

32 95

32

95

32

95

315

315

95 315

32

95

39 

Table 3-2 Levels of Significant Exposure to Inorganic Tin - Oral (continued) 

Exposure/ 

Duration/ a Frequency Key to Species (Route) Figure (Strain) 

12 Rat 

(Wistar) 

13 wk 

7 d/wk 

(F) 

13 Rat 

(Wistar) 

13 wk 

ad libitum 

(F) 

System 

Cardio 

Hemato 

Hepatic 

Renal 

Bd Wt 

Cardio 

Gastro 

Hemato 

Hepatic 

Renal 

Endocr 

Bd Wt 

Other 

LOAEL 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

Serious 

(mg/kg/day) 

Reference 

Chemical Form 

440 DeGroot et al. 1973 

SnO 

440 

440 

440 

440 

315 DeGroot et al. 1973 

SnCl2 

32 

b

32 

95 

95 

(abdominal distension) 

(reduced hemoglobin 

concentration) 

32 95 (bile duct epithelium 

proliferation) 

315 

315 

95 

32 95 (14% reduced food 

consumption on week 2) 

315 (weight loss) 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
105

85

85

85

85

85

106

390

390

390

390

390

40 

Table 3-2 Levels of Significant Exposure to Inorganic Tin - Oral (continued) 

a Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference 

Chemical Form 

14 Rat 

(Wistar) 

4 wk 

7 d/wk 

(F) 

Cardio 85 DeGroot et al. 1973 

Sn(Cl8H3302) 

Hemato 

Hepatic 

Renal 

Bd Wt 

85 

85 

85 

85 

15 Rat 

(Wistar) 

4 wk 

7 d/wk 

(F) 

Cardio 390 DeGroot et al. 1973 

SnO2 

Hemato 

Hepatic 

Renal 

Bd Wt 

390 

390 

390 

390 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
107

275

275

28

83

83

275

275

28

83

108

220

22

66

66

220

220

22

66

41 

Table 3-2 Levels of Significant Exposure to Inorganic Tin - Oral (continued) 

Exposure/ 

Duration/ 

a Frequency Key to Species (Route) Figure (Strain) 

16 Rat 

(Wistar) 

4 wk 

7 d/wk 

(F) 

17 Rat 

(Wistar) 

4 wk 

7 d/wk 

(F) 

System 

Cardio 

Gastro
 

Hemato
 

Hepatic
 

Renal
 

Bd Wt
 

Cardio
 

Hemato
 

Hepatic
 

Renal
 

Bd Wt
 

LOAEL 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

Serious 

(mg/kg/day) 

Reference 

Chemical Form 

275 DeGroot et al. 1973 

SnSO4 

275 

28 83 (decreased hemoglobin 

and hematocrit) 

83 275 (slightly decreased 

liver/body weight ratio, 

homogenous cell 

cytoplasm) 

275 

28 83 (16% decreased body 

weight gain and 

decreased food intake in 

males) 

220 DeGroot et al. 1973 

SnC4-H406 

22 66 (decreased hemoglobin 

and hematocrit) 

66 220 (bile duct hyperplasia, 

homogenous cell 

cytoplasm) 

220 

22 66 (11% decreased body 

weight gain in males) 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
110

285

29

86

29

86

285

29

86

42 

Table 3-2 Levels of Significant Exposure to Inorganic Tin - Oral (continued) 

a Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference 

Chemical Form 

18 Rat 

(Wistar) 

4 wk 

7 d/wk 

(F) 

Cardio 285 DeGroot et al. 1973 

SnC204 

Hemato 29 86 (decreased hemoglobin 

and hematocrit) 

Hepatic 29 86 (bile duct hyperplasia, 

homogenous cell 

cytoplasm) 

Renal 285 

Bd Wt 29 86 (18-25% decreased body 

weight gain and 

decreased food intake) 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
98

315

95

315

32

95

32

95

315

32

95

99

390

117

390

390

390

390

43 

Table 3-2 Levels of Significant Exposure to Inorganic Tin - Oral	 (continued) 

Exposure/ 

Duration/ a Frequency Key to Species (Route) Figure (Strain) 

19 Rat 

(Wistar) 

4 wk 

7 d/wk 

(F) 

20 Rat 

(Wistar) 

4 wk 

7 d/wk 

(F) 

System 

Cardio 

Gastro 

Hemato 

Hepatic 

Renal
 

Other
 

Cardio 

Hemato 

Hepatic 

Renal 

Bd Wt 

LOAEL 

NOAEL Less Serious Reference 	 Serious 

(mg/kg/day)	 (mg/kg/day) (mg/kg/day) Chemical Form 

315	 DeGroot et al. 1973 

SnCl2 

95 315	 (slightly distended small
 

and large intestines)
 

32 95	 (decreased hemoglobin
 

and hematocrit)
 

32 95	 (bile duct hyperplasia,
 

homogeneous cell
 

cytoplasm)
 

315 

32 95	 (30% decreased body
 

weight gain and
 

decreased food intake)
 

390	 DeGroot et al. 1973 

SnS 

117 390	 (significant increase in
 

hematocrit in males)
 

390 

390 

390 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
102

7.9

7.9

7.9

111

2457

157

311

2457

2457

2457

157

2138

10

44 

Table 3-2 Levels of Significant Exposure to Inorganic Tin - Oral (continued) 

a Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference 

Chemical Form 

21 Rat 

(Wistar) 

4 wk 

ad libitum 

(F) 

Gastro 7.9 M (increased intestinal 

length) 

Janssen et al. 1985 

SnCl2 

Hemato 7.9 M (decreased hemoglobin 

concentration) 

Bd Wt 7.9 M (17% reduction in final 

body weight) 

22 Mouse 

(B6C3F1) 

13 wk 

7 d/wk 

(F) 

Cardio 2457 NTP 1982 

SnCl2 

Gastro 157 311 (gross distention of the 

cecum) 

Hemato 

Hepatic 

Renal 

Bd Wt 

2457 

2457 

2457 

157 (11.7% decreased body 

weight gain in males) 

23 Rabbit 

(NS) 

4 mo 

1 x/d 

(G) 

Hemato 10 F (transient hemolytic 

anemia) 

Chmielnicka et al.1993 

SnCl2 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
2205

56

2211

45

2204

56

2212

45

112

0.7

45 

Table 3-2 Levels of Significant Exposure to Inorganic Tin - Oral (continued) 

a Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference 

Chemical Form 

Reproductive 

24 Rat 

(SpragueDawley) 

20 d 

Gd 0-20 

ad libitum 

(F) 

56 F Theuer et al. 1971 

SnF2 

25 Rat 

(SpragueDawley) 

20 d 

Gd 0-20 

ad libitum 

(F) 

45 Theuer et al. 1971 

NaSn2Cl5 

Developmental 

26 Rat 

(SpragueDawley) 

20 d 

Gd 0-20 

ad libitum 

(F) 

56 F Theuer et al. 1971 

SnF2 

27 Rat 

(SpragueDawley) 

20 d 

Gd 0-20 

ad libitum 

(F) 

45 Theuer et al. 1971 

NaSn2Cl5 

CHRONIC EXPOSURE 

Death 

28 Rat 

(Long- Evans) 

42 mo 

7 d/wk 

(W) 

0.7 (decreased longevity in 

females by 11%) 

Schroeder et al. 1968 

SnCl2 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
114

63

63

63

63

63

115

0.7

0.7

0.7

117

164

164

164

164

46 

Table 3-2 Levels of Significant Exposure to Inorganic Tin - Oral	 (continued) 

Exposure/ 

Duration/ a Frequency Key to	 Species (Route) Figure (Strain) 

Systemic 

29 Rat 

(Fischer- 344) 

30	 Rat 

(Long- Evans) 

31	 Mouse 

(B6C3F1) 

105 wk 

7 d/wk 

(F) 

42 mo 

7 d/wk 

(W) 

105 wk 

7 d/wk 

(F) 

System 

Cardio 

Gastro 

Hepatic 

Renal 

Bd Wt 

Hepatic 

Renal 

Bd Wt 

Cardio 

Gastro 

Hepatic 

Bd Wt 

NOAEL 

(mg/kg/day) 

63 

63 

63 

63 

63 

164 

164
 

164
 

164
 

LOAEL 

Less Serious	 Serious 

(mg/kg/day)	 (mg/kg/day) 

0.7	 (fatty degeneration) 

0.7	 (tubular degeneration, 

vacuolization) 

0.7	 (11-16% decreased body 

weight, compared to 

controls) 

Reference 

Chemical Form 

NTP 1982 

SnCl2 

Schroeder et al. 1968 

SnCl2 

NTP 1982 

SnCl2 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
116

0.7

47 

Table 3-2 Levels of Significant Exposure to Inorganic Tin - Oral (continued) 

a Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference 

Chemical Form 

32 Mouse 

(albino) 

18 mo 

7 d/wk 

(W) 

Bd Wt 0.7 Schroeder et al. 1968 

SnCl2 

a The number corresponds to entries in Figure 3-2. 

b Used to derive an intermediate-duration oral minimal risk level (MRL) of 0.3 mg/kg/day; the MRL was derived by dividing the NOAEL by an uncertainty factor of 100 (10 for animal 

to human extrapolation and 10 for human variability). 

Cardio = cardiovascular; d = day(s); Derm = dermal; (F) = feed; (GW) = gavage in water; Gastro = gastrointestinal; Hemato = hematological; LOAEL = 

lowest-observed-adverse-effect level; M = males; mo = month(s); NOAEL = no-observed-adverse-effect level; SnC2O4 = stannous oxalate; SnC4H4O6 = stannous tartrate; 

Sn(C18H33O2)2 = stannous oleate; SnCl2 = stannous chloride; SnO2 = stannic oxide; Sn2O7N2 = stannous nitrate; Sn3(PO4)2 = stannous orthophosphate; SnS = stannous sulfide; 

SnSO4 = stannous sulfate; (W) = water; wk = week(s) 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
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T&RZ D6KHHS J*XLQHD3LJ &DQFHU

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
'HDWK

&DUGLRYDVFXODU*DVWURLQWHVWLQDO+HSDWL5HQDO%RG\

F

:HLJKW

51 

)LJXUH/HYHOVRI6LJQLILFDQW([SRVXUHWR,QRUJDQLF7LQ2UDO &RQWLQXHG

&KURQLFGD\V

6\VWHPLF

PJNJGD\



P P P P



U U U U U





U U U P U



F&DW +XPDQV I)HUUHW Q0LQN &DQFHU(IIHFW/HYHO$QLPDOV &DQFHU(IIHFW/HYHO+XPDQV /'/&

G'RJ N0RQNH\ M3LJHRQ R2WKHU /2$(/0RUH6HULRXV$QLPDOV /2$(/0RUH6HULRXV+XPDQV 0LQLPDO5LVN /HYHO

U5DW P0RXVH H*HUELO /2$(//HVV6HULRXV$QLPDOV /2$(//HVV6HULRXV+XPDQV IRUHIIHFWV

S3LJ K5DEELW V+DPVWHU 12$(/$QLPDOV 12$(/+XPDQV RWKHUWKDQ

T&RZ D6KHHS J*XLQHD3LJ &DQFHU

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
2097

20

147

50

2080

7.5

2153

23

152

50

50

2102

20 40

52 

Table 3-3 Levels of Significant Exposure to Dibutyltins - Oral 

a Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) 

ACUTE EXPOSURE 

Death 

1 Rat 

(NS) 

3 d 

1 x/d 

(GO) 

System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

20 F (4/20 deaths 24 hours 

after dosing) 

Reference 

Chemical Form 

Alam et al. 1993 

DBT 

2 Rat 

(Wistar) 

4 d 

1x/d 

(GO) 

50 (death of 30%-50%) Barnes and Magee 1958 

DBT 

3 Rat 

(Wistar) 

Gd 7-15 

1 x/d 

(GO) 

7.5 F (5 out 12 pregnant rats 

died) 

Ema et al. 1991b 

DBT 

4 Rat 

(Wistar) 

2 wk 

ad libitum 

(F) 

23 (4 females and 2 males 

died 

in second week) 

Seinen et al. 1977a 

DBT 

Systemic 

5 Rat 

(Wistar) 

4 d 

1x/d 

(GO) 

Gastro 50 (distention of stomach) Barnes and Magee 1958 

DBT 

Hepatic 50 (bile duct necrosis) 

6 Rat 

(Wistar) 

3 d 

1 x/d 

(GO) 

Bd Wt 20 F (reduced body weight 

gain) 

40 F (significant body weight 

loss) 

Khaliq et al. 1991 

DBT 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
2152

7.7

23

7.7

23

2228

18.3

2242

9.2 18.3

2226

58.6

2222

36.6

157

30

2154

7.7

53 

Table 3-3 Levels of Significant Exposure to Dibutyltins - Oral (continued) 

a Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference 

Chemical Form 

7 Rat 

(Wistar) 

2 wk 

ad libitum 

(F) 

Hepatic 7.7 23 (proliferation of bile duct 

epithelium; periportal 

fibrosis) 

Seinen et al. 1977a 

DBT 

Bd Wt 7.7 23 (20% reduced final body 

weight) 

8 Rat 

(Wistar) 

once 

(GO) Hepatic 18.3 M (increased serum AST 

and ALT activities) 

Ueno et al. 2003b 

DBT 

9 Mouse 

(albino) 

once 

(GO) Hepatic 9.2 M 18.3 M (liver damage) Ueno et al. 1995 

DBT 

10 Mouse 

(albino) 

once 

(GO) Hepatic 58.6 M (liver necrosis) Ueno et al. 2003b 

DBT 

11 Gn Pig 

(Hartley) 

once 

(GO) Hepatic 36.6 M Ueno et al. 2003a 

DBT 

12 Hamster 

(Golden 

Syrian) 

Immuno/ Lymphoret 

13 Rat 

(Wistar) 

1 d 

1x/d 

(GO) 

2 wk 

ad libitum 

(F) 

Hepatic 30 M (bile duct necrosis) 

7.7 (over 50% reduced 

relative thymus weight; 

lymphocyte depletion in 

lymphoid organs) 

Jang et al. 1986 

DBT 

Seinen et al. 1977a 

DBT 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
2114

3.8

2078

5

7.5

2081

20

2218

7.6

2028

10

2085

10

15

54 

Table 3-3 Levels of Significant Exposure to Dibutyltins - Oral (continued) 

a Key to 

Figure 

Species 

(Strain) 

Reproductive 

14 Rat 

(Wistar) 

Exposure/ 

Duration/ 

Frequency 

(Route) 

Gd 4-7 

1 x/d 

(GO) 

System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

3.8 F (significant increase in 

postimplantation loss) 

Reference 

Chemical Form 

Ema and Harazono 2000 

DBT 

15 Rat 

(Wistar) 

Gd 7-15 

1 x/d 

(GO) 

5 F 7.5 F (increased resorptions, 

dead fetuses, and 

postimplantation loss) 

Ema et al. 1991b 

DBT 

16 Rat 

(Wistar) 

Gd 7-9 

1 x/d 

(GO) 

20 F (increased resorptions, 

dead fetuses, and 

postimplantation loss) 

Ema et al. 1992 

DBT 

17 Rat 

(Wistar) 

Gd 0-3 

1 x/d 

(GO) 

7.6 F (reduced fertility rate; 

increased 

pre-implantation loss) 

Ema et al. 2003 

DBT 

18 Rat 

(Wistar) 

Gd 6-15 

1 x/d 

(GO) 

10 F Farr et al. 2001 

DBT 

19 Rat 

(Wistar) 

Gd 7-17 

1 x/d 

(GO) 

10 F 15 F (increased incidence of 

dead or 

resorbed fetuses) 

Noda et al. 1992b 

DBT 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
2115

3.8

7.6

2079

2.5

5

2082

20

2027

5

10

2086

5

10

55 

Table 3-3 Levels of Significant Exposure to Dibutyltins - Oral (continued) 

a Key to 

Figure 

Species 

(Strain) 

Developmental 

20 Rat 

(Wistar) 

Exposure/ 

Duration/ 

Frequency 

(Route) 

Gd 4-7 

1 x/d 

(GO) 

System 

NOAEL 

(mg/kg/day) 

3.8 

Less Serious 

(mg/kg/day) 

7.6 (significantly reduced 

fetal body weight) 

LOAEL 

Serious 

(mg/kg/day) 

Reference 

Chemical Form 

Ema and Harazono 2000 

DBT 

21 Rat 

(Wistar) 

Gd 7-15 

1 x/d 

(GO) 

2.5 5 (increased incidence of 

external and skeletal 

malformations) 

Ema et al. 1991b 

DBT 

22 Rat 

(Wistar) 

Gd 7-9 

1 x/d 

(GO) 

20 (increased incidence of 

malformations) 

Ema et al. 1992 

DBT 

23 Rat 

(Wistar) 

Gd 6-15 

1 x/d 

(GO) 

5 10 (slight increase in 

malformations) 

Farr et al. 2001 

DBT 

24 Rat 

(Wistar) 

Gd 7-17 

1 x/d 

(GO) 

5 10 (increased external and 

skeletal malformations) 

Noda et al. 1992b 

DBT 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
2149

3.4

5.7

5.7

5.7

5.7

5.7

119

17.5

2159

30

30

30

30

2165

5

2160

30

56 

Table 3-3 Levels of Significant Exposure to Dibutyltins - Oral (continued) 

a Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) 

INTERMEDIATE EXPOSURE 

Systemic 

25 Rat 

(Fischer- 344) 

90 d 

ad libitum 

(F) 

System 

Hemato 

NOAEL 

(mg/kg/day) 

3.4 M 

LOAEL 

Less Serious 

(mg/kg/day) 

Serious 

(mg/kg/day) 

5.7 F (8% reduced hemoglobin 

concentration) 

Reference 

Chemical Form 

Gaunt et al. 1968 

DBT 

Hepatic 

Renal 

5.7 F 

5.7 F 

Endocr 5.7 F 

Bd Wt 5.7 F 

26 Rat 

(albino) 

15 d 

1 x/d 

(GO) 

Hepatic 17.5 M (increased heme 

oxygenase activity, 

decreased activity of 

microsomal enzymes) 

Mushtaq et al 1981 

DBT 

27 Mouse 

(SwissWebster) 

4 wk 

ad libitum 

(F) 

Hepatic 30 M Seinen et al. 1977a 

DBT 

Renal 30 M 

Endocr 30 M 

Immuno/ Lymphoret 

28 Rat 

(Wistar) 

4-6 wk 

ad libitum 

(F) 

Bd Wt 30 M 

b

5 M (depressed humoral 

response against SRBC) 

Seinen et al. 1977b 

DBT 

29 Mouse 

(SwissWebster) 

4 wk 

ad libitum 

(F) 

30 M Seinen et al. 1977a 

DBT 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
2169

29

205

6.65

209

19.76

2161

6.65

6.65

6.65

6.65

6.65

6.65

6.65

6.65

218

19.76

19.76

19.76

19.76

Table 3-3 Levels of Significant Exposure to Dibutyltins - Oral (continued) 

a Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference 

Chemical Form 

30 Mouse 

(SwissWebster) 

4 wk 

ad libitum 

(F) 

CHRONIC EXPOSURE 

Death 

31 Rat 

(Fischer- 344) 

78 wk 

ad libitum 

(F) 

29 M 

6.65 M (52% survival at 

termination 

compared to 85% in 

controls) 

Seinen et al. 1977b 

DBT 

NCI 1978a 

DBT 

32 Mouse 

(B6C3F1) 

78 wk 

ad libitum 

(F) 

19.76 F (86% survival compared 

with 95% in controls) 

NCI 1978a 

DBT 

Systemic 

33 Rat 

(Fischer- 344) 

78 wk 

ad libitum 

(F) 

Resp 6.65 NCI 1978a 

DBT 

Cardio 6.65 

Gastro 6.65 

Hepatic 

Renal 

6.65 

6.65 

Endocr 6.65 

Dermal 6.65 

Bd Wt 6.65 

34 Mouse 

(B6C3F1) 

78 wk 

ad libitum 

(F) 

Resp 19.76 NCI 1978a 

DBT 

Cardio 19.76 

Gastro 19.76 

Hepatic 19.76 

TIN AND TIN COMPOUNDS 57 

3. HEALTH EFFECTS 
19.76

19.76

19.76

19.76

58 

Table 3-3 Levels of Significant Exposure to Dibutyltins - Oral (continued) 

Exposure/ LOAEL
 

Duration/
 a Key to Species Frequency NOAEL Less Serious Serious Reference 

(Route) Figure (Strain) System (mg/kg/day) (mg/kg/day) (mg/kg/day) Chemical Form 

Renal 19.76 

Endocr 19.76 

Dermal 19.76 

Bd Wt 19.76 

a The number corresponds to entries in Figure 3-3. 

b Used to derive an intermediate-duration oral minimal risk level (MRL) of 0.005 mg/kg/day; The MRL was derived by dividing the LOAEL by an uncertainty factor of 1000 (10 for the 

use of a LOAEL, 10 for animal to human extrapolation and 10 for human variability). 

Bd Wt = body weight; Cardio = cardiovascular; d = day(s); Endocr = endocrine; (F) = feed; F = Female; Gastro = gastrointestinal; gd = gestational day; (GO) = gavage in oil; hemato = 

hematological; LOAEL = lowest-observed-adverse-effect level; M = male; NOAEL = no-observed-adverse-effect level; Resp = respiratory; x = time(s); wk = week(s) 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
Death 

Gastrointestinal Hepatic Body WImmuno/LReproductive Developmental 

eight 

ymphor 

Figure 3-3 Levels of Significant Exposure to Dibutyltins - Oral 

Acute (≤14 days) 

Systemic 

mg/kg/day 

100 

10m 

2r 5r 5r 

6r 

11g 

12s 

4r 7r 7r 

1r 6r 16r 22r 

9m 8r 

19r 

10 18r 19r 23r 24r 

9m 

3r 7r 7r 13r 15r 17r 20r

15r 21r 23r 24r 

14r 20r 

21r 

1 

c-Cat 

d-Dog

r-Rat 

p-Pig

q-Cow

 -Humans 

k-Monkey

m-Mouse 

h-Rabbit 

a-Sheep 

f-Ferret 

j-Pigeon

e-Gerbil 

s-Hamster 

g-Guinea Pig 

n-Mink 

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

LOAEL, Less Serious-Animals

 NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

LOAEL, Less Serious-Humans

 NOAEL - Humans

 LD50/LC50

Minimal Risk Level

 for effects

 other than

 Cancer 

TIN AND TIN COMPOUNDS 59 

3. HEALTH EFFECTS 
Hematological 

Hepatic 

Renal Endocrine Body Weight 

Figure 3-3 Levels of Significant Exposure to Dibutyltins - Oral (Continued) 

Intermediate (15-364 days) 

Systemic mg/kg/day 

Immuno/Lymphor 

100 

27m 27m 27m 27m 29m 30m 

26r 

10 

25r 25r 25r 25r 25r 28r 

25r 

1 

0.1 

0.01 

0.001 

c-Cat 

d-Dog

r-Rat 

p-Pig

q-Cow

 -Humans 

k-Monkey

m-Mouse 

h-Rabbit 

a-Sheep 

f-Ferret 

j-Pigeon

e-Gerbil 

s-Hamster 

g-Guinea Pig 

n-Mink 

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

LOAEL, Less Serious-Animals

 NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

LOAEL, Less Serious-Humans

 NOAEL - Humans

 LD50/LC50

Minimal Risk Level

 for effects

 other than

 Cancer 

TIN AND TIN COMPOUNDS 60 

3. HEALTH EFFECTS 
Death 

Respiratory Cardiovascular Gastrointestinal Hepatic Renal Endocrine Dermal Body Weight 

Figure 3-3 Levels of Significant Exposure to Dibutyltins - Oral (Continued) 

Chronic (≥365 days) 

Systemic mg/kg/day 

100 

32m 34m 34m 34m 34m 34m 34m 34m 34m 

10 

31r 33r 33r 33r 33r 33r 33r 33r 33r 

1 

c-Cat 

d-Dog

r-Rat 

p-Pig

q-Cow

 -Humans 

k-Monkey

m-Mouse 

h-Rabbit 

a-Sheep 

f-Ferret 

j-Pigeon

e-Gerbil 

s-Hamster 

g-Guinea Pig 

n-Mink 

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

LOAEL, Less Serious-Animals

 NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

LOAEL, Less Serious-Humans

 NOAEL - Humans

 LD50/LC50

Minimal Risk Level

 for effects

 other than

 Cancer 

TIN AND TIN COMPOUNDS 61 

3. HEALTH EFFECTS 
2155

23

23

23

7.7

23

2156

7.7

2168

7

62 

Table 3-4 Levels of Significant Exposure to Dioctyltins - Oral 

a Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) 

ACUTE EXPOSURE 

Systemic 

1 Rat 

(Wistar) 

2 wk 

ad libitum 

(F) 

System 

Hepatic 

NOAEL 

(mg/kg/day) 

23 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference 

Chemical Form 

Seinen et al. 1977a 

DOT 

Renal 23 

Endocr 23 

Bd Wt 7.7 F 23 F (12% reduced final body 

weight) 

Immuno/ Lymphoret 

2 Rat 

(Wistar) 

2 wk 

ad libitum 

(F) 

7.7 (over 35% reduction in 

relative thymus weight; 

lymphocyte depletion in 

lymphoid organs) 

Seinen et al. 1977a 

DOT 

INTERMEDIATE EXPOSURE 

Death 

3 Gn Pig 

(Hartley) 

5-7 wk 

ad libitum 

(F) 

7 F (10 of 16 deaths on 

weeks 4-5) 

Seinen et al. 1977b 

DOT 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
2162

5.3

16

5.3

16

16

16

5.3

16

16

16

2174

100

500

63 

Table 3-4 Levels of Significant Exposure to Dioctyltins - Oral (continued) 

a Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) 

LOAEL 

System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

Serious 

(mg/kg/day) 

Reference 

Chemical Form 

Systemic 

4 Rat 

(Wistar) 

6 wk 

ad libitum 

(F) 

Resp 5.3 F 16 F (gross changes 

suggesting chronic 

respiratory disease) 

Seinen and Willems 1976 

DOT 

Hemato 5.3 16 M (decrease hemoglobin 

concentration) 

Musc/skel 16 

Hepatic 16 

Renal 5.3 16 M (functional changes 

suggesting renal 

impairment) 

Dermal 16 

Bd Wt 16 

5 Mouse 

(BALB/c) 

8 wk 

1 x/wk 

(GO) 

Hemato 100 F 500 F (14% reduction in mean 

hemoglobin 

concentration). 

Miller et al. 1986 

DOT 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
2157

4 8

8

8

8

4 8

2163

5.3

2166

5

2173

100

500

2158

4

8

64 

Table 3-4 Levels of Significant Exposure to Dioctyltins - Oral	 (continued) 

Exposure/ 

Duration/ a Frequency Key to Species (Route) Figure (Strain) 

6 Gn Pig 4 wk 

(Hartley) ad libitum 

(F) 

Immuno/ Lymphoret 

7 Rat 6 wk 

(Wistar) ad libitum

(F) 

8 Rat	 4-6 wk 

(Wistar) ad libitum

(F) 

9 Mouse	 8 wk 

1 x/wk (BALB/c) 

(GO) 

10 Gn Pig	 4 wk 

(Hartley) ad libitum

(F) 

System 

Gastro 

Hepatic 

Renal 

Endocr 

Bd Wt 

NOAEL 

(mg/kg/day) 

4 M 

8 M 

8 M 

8 M 

100 F 

4 M 

Less Serious 

(mg/kg/day) 

8 M (abdominal edema) 

4 M (13% reduced final body 

weight) 

5 M (impaired cell-mediated 

immunity; lymphocyte 

depletion from thymus) 

8 M (lymphocyte depletion in 

thymic cortex) 

LOAEL 

Serious 

(mg/kg/day) 

8 M (43% reduced final body 

weight) 

5.3	 (thymus atrophy;
 

lymphocyte depletion in
 

thymic cortex)
 

500 F	 (67% reduction in relative 

thymus weight) 

Reference 

Chemical Form 

Seinen et al. 1977a 

DOT 

Seinen and Willems 1976 

DOT 

Seinen et al. 1977b 

DOT 

Miller et al. 1986 

DOT 

Seinen et al. 1977a 

DOT 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
2167

7

65 

Table 3-4 Levels of Significant Exposure to Dioctyltins - Oral (continued) 

a Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference 

Chemical Form 

11 Gn Pig 

(Hartley) 

5-7 wk 

ad libitum 

(F) 

7 F Seinen et al. 1977b 

DOT 

a The number corresponds to entries in Figure 3-4. 

Bd Wt = body weight; Endocr = endocrine; (F) = feed; F = Female; Gastro = gastrointestinal; (GO) = gavage in oil; hemato = hematological; Immuno = immunological; LOAEL = 

lowest-observed-adverse-effect level; M = male; NOAEL = no-observed-adverse-effect level; Resp = respiratory; x = time(s); wk = week(s) 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
Hepatic 

Renal 

Endocrine 

Body WImmuno/L

100 

eight 

ymphor 

Figure 3-4 Levels of Significant Exposure to Dioctyltins - Oral 

Acute (≤14 days) 

mg/kg/day Systemic 

TIN AND TIN COMPOUNDS 66 

1r 1r 1r 

3. HEALTH EFFECTS 

10 

1 

c-Cat 

d-Dog

r-Rat 

p-Pig

q-Cow

 -Humans 

k-Monkey

m-Mouse 

h-Rabbit 

a-Sheep 

f-Ferret 

j-Pigeon

e-Gerbil 

s-Hamster 

g-Guinea Pig 

n-Mink 

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

LOAEL, Less Serious-Animals

 NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

LOAEL, Less Serious-Humans

 NOAEL - Humans

 LD50/LC50

Minimal Risk Level

 for effects

 other than

 Cancer 

1r 

1r 2r 
Death 

Respiratory Gastrointestinal Hematological Musculoskeletal Hepatic Renal Endocrine 

Dermal 

Body WImmuno/L

eight 

ymphor 

Figure 3-4 Levels of Significant Exposure to Dioctyltins - Oral (Continued) 

Intermediate (15-364 days) 

Systemic mg/kg/day 

1000 

5m 9m 

100 5m 9m 

4r 4r 4r 4r 4r 4r 4r 

10 

6g 6g 6g 6g 6g 10g 3g 11g 

4r 4r 4r 7r 8r 

6g 6g 10g 

1 

c-Cat 

d-Dog

r-Rat 

p-Pig

q-Cow

 -Humans 

k-Monkey

m-Mouse 

h-Rabbit 

a-Sheep 

f-Ferret 

j-Pigeon

e-Gerbil 

s-Hamster 

g-Guinea Pig 

n-Mink 

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

LOAEL, Less Serious-Animals

 NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

LOAEL, Less Serious-Humans

 NOAEL - Humans

 LD50/LC50

Minimal Risk Level

 for effects

 other than

 Cancer 

TIN AND TIN COMPOUNDS 67 

3. HEALTH EFFECTS 
2070

9

2246

50

2223

50

2133

6.7

20

2067

3.1

4.7

2072

3.1

6.3

2074

3.1

4.7

68 

Table 3-5 Levels of Significant Exposure to Triphenyltins - Oral 

a Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) 

ACUTE EXPOSURE 

Death 

1 Rat 

(Wistar) 

Gd 7-17 

1 x/d 

(GO) 

System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

9 F (mortality in pregnant 

rats) 

Reference 

Chemical Form 

Noda et al. 1991b 

TPT 

Systemic 

2 Hamster 

(Golden 

Syrian) 

once 

(GO) Endocr 50 M (hyperglicemia and 

hypertriglyceridemia) 

Ohhira and Matsui 1996 

TPT 

3 Hamster 

(Golden 

Syrian) 

once 

(GO) Endocr 50 M (increased serum 

glucose and triglycerides) 

Ohhira et al. 1999 

TPT 

Immuno/ Lymphoret 

4 Rat 

(Wistar) 

2 wk 

ad libitum 

(F) 

6.7 M 20 M (19% reduction in thymus 

weight) 

Snoeij et al. 1985 

TPT 

Reproductive 

5 Rat 

(Wistar) 

Gd 0-3 

1 x/d 

(GO) 

3.1 F 4.7 F (infertility and 

preimplantation loss) 

Ema et al. 1997b 

TPT 

6 Rat 

(Wistar) 

Gd 7-9 

1x/d 

(GO) 

3.1 F 6.3 F (increased resorptions, 

dead fetuses, and 

postimplantation loss) 

Ema et al. 1999a 

TPT 

7 Rat 

(Wistar) 

Gd 0-3 

1 x/d 

(GO) 

3.1 F 4.7 F (reduced uterine weight 

and serum progesterone) 

Ema et al. 1999b 

TPT 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
2069

3 6

2068

3.1

4.7

2073

6.3

9.4

2170

23.2

2172

60

2171

5

69 

Table 3-5 Levels of Significant Exposure to Triphenyltins - Oral (continued) 

a Key to 

Figure 

Species 

(Strain) System 

Exposure/ 

Duration/ 

Frequency 

(Route) 

LOAEL 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

Serious 

(mg/kg/day) 

Reference 

Chemical Form 

8 Rat 

(Wistar) 

Gd 7-17 

1 x/d 

(GO) 

Developmental 

9 Rat 

(Wistar) 

Gd 0-3 

1 x/d 

(GO) 

3 F 6 F (fetal resorption) 

3.1 4.7 (reduced fetal body 

weight) 

Noda et al. 1991b 

TPT 

Ema et al. 1997b 

TPT 

10 Rat 

(Wistar) 

Gd 13-15 

1 x/d 

(GO) 

6.3 9.4 (decreased body weight 

of live fetuses) 

Ema et al. 1999a 

TPT 

INTERMEDIATE EXPOSURE 

Death 

11 Rat 

(Fischer- 344) 

7 wk 

ad libitum 

(F) 

23.2 (10/10 rats died) NCI 1978b 

TPT 

12 Mouse 

(B6C3F1) 

7 wk 

ad libitum 

(F) 

Systemic 

13 Bd Wt Rat 

(Fischer- 344) 

7 wk 

ad libitum 

(F) 

60 (10/10 died) 

5 (25% reduction in body 

weight gain) 

NCI 1978b 

TPT 

NCI 1978b 

TPT 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
2065

8.7

17.4

8.7

17.4

1.7

8.7 17.4

186

1.25

2066

8.7

17.4

207

0.4

210

4.88

70 

Table 3-5 Levels of Significant Exposure to Triphenyltins - Oral (continued) 

a Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference 

Chemical Form 

14 Rabbit 

(New 

Zealand) 

70 d 

ad libitum 

(F) 

Hepatic 8.7 M 17.4 M (hypertrophy of smooth 

endoplasmic reticulum) 

Dacasto et al. 1994 

TPT 

Renal 8.7 M 17.4 M (slight vacuolization of 

tubular epithelium) 

Bd Wt 1.7 M 8.7 M (more than 10% 

reduction in final body 

weight) 

17.4 M (more than 20% 

reduction in final body 

weight) 

Immuno/ Lymphoret 

15 Rat 

(Wistar) 

3-4 wk 

(F) 1.25 M (changes in immune 

response) 

Vos et al 1984b 

TPT 

16 Rabbit 

(New 

Zealand) 

70 d 

ad libitum 

(F) 

8.7 M 17.4 M (depletion of lymphocytes 

in thymic cortex) 

Dacasto et al. 1994 

TPT 

CHRONIC EXPOSURE 

Death 

17 Rat 

(Wistar) 

104 wk 

ad libitum 

(F) 

0.4 F (51% survival vs. 75% in 

controls) 

Tennekes et al. 1989b 

TPT 

18 Mouse 

(B6C3F1) 

78 wk 

ad libitum 

(F) 

4.88 M (74% survival vs. 95% in 

controls) 

NCI 1978b 

TPT 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
208

20.16

212

3.75

3.75

3.75

3.75

3.75

3.75

3.75

3.75

71 

Table 3-5 Levels of Significant Exposure to Triphenyltins - Oral (continued) 

a Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference 

Chemical Form 

19 Mouse 

(Hybrid) 

80 wk 

ad libitum 

(F) 

Tennekes et al. 1989a 

TPT 

20.16 F (50% survival vs. 74% in 

controls) 

Systemic 

20 Rat 

(Fischer- 344) 

78 wk 

ad libitum 

(F) 

Resp 3.75 NCI 1978b 

TPT 

Cardio 3.75 

Gastro 3.75 

Hepatic 

Renal 

3.75 

3.75 

Endocr 3.75 

Dermal 3.75 

Bd Wt 3.75 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
211

6.2

6.2

6.2

6.2

0.4

6.2

0.4

6.2

6.2

215

6.2

0.4

1.3

0.4

6.2

0.4 1.3

72 

Table 3-5 Levels of Significant Exposure to Triphenyltins - Oral (continued) 

a Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference 

Chemical Form 

21 Rat 

(Wistar) 

104 wk 

(F) Cardio 6.2 F Tennekes et al. 1989b 

TPT 

Gastro 6.2 

Hemato 6.2 F 

Musc/skel 

Hepatic 

Renal 

6.2 F 

6.2 F 

0.4 F (bile duct proliferation) 

Endocr 0.4 F (cystoid lesions and 

hyperplasia of the 

pituitary) 

Ocular 6.2 

Bd Wt 6.2 

22 Rat 

(Wistar) 

52 wk 

(F) Cardio 6.2 Tennekes et al. 1989b 

TPT 

Hemato 0.4 1.3 (significant decrease in 

hemoglobin and 

hematocrit in females; 

increased prothrombin 

time in males) 

Hepatic 

Renal 6.2 

0.4 F (bile duct proliferation) 

Endocr 0.4 1.3 (cystoid pituitary lesions) 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
216

9.75

9.75

9.75

9.75

9.75

9.75

9.75

9.75

73 

Table 3-5 Levels of Significant Exposure to Triphenyltins - Oral (continued) 

a Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference 

Chemical Form 

23 Mouse 

(B6C3F1) 

78 wk 

ad libitum 

(F) 

Resp 9.75 NCI 1978b 

TPT 

Cardio 9.75 

Gastro 9.75 

Hepatic 9.75 

Renal 9.75 

Endocr 9.75 

Dermal 9.75 

Bd Wt 9.75 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
217

20.16

4.56

20.16

20.16

20.16

4.56

15.24

20.16

20.16

20.16

20.16

4.56

15.24

74 

Table 3-5 Levels of Significant Exposure to Triphenyltins - Oral	 (continued) 

a Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

24 Mouse 

(Hybrid) 

80 wk 

ad libitum 

(F) 

Cardio 

Gastro 

Hemato 

Musc/skel 

Hepatic 

Renal 

Endocr 

Dermal 

Ocular 

Bd Wt 

LOAEL 

Reference 

(mg/kg/day) (mg/kg/day) (mg/kg/day) Chemical Form 

NOAEL Less Serious	 Serious 

20.16	 Tennekes et al. 1989a 

TPT 

4.56 F 

20.16 

20.16 

20.16 F 

4.56 F 15.24 M (35-40% increase relative
 

liver weight)
 

20.16 

20.16 

20.16	 (skin lesions, females
 

more sensitive than
 

males)
 

20.16 

4.56 F 15.24 M (11% reduced final body
 

weight)
 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
219

0.62

0.62

0.62

0.62

0.62

0.62

0.62

0.62

0.62

0.62

0.62

220

0.3

223

6.2

227

15.24

75 

Table 3-5 Levels of Significant Exposure to Triphenyltins - Oral (continued) 

a Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference 

Chemical Form 

25 Dog 

(Beagle) 

52 wk 

(F) Resp 0.62 Sachsse et al 1987 

TPT 

Cardio 0.62 

Gastro 0.62 

Hemato 0.62 

Musc/skel 0.62 

Hepatic 0.62 

Renal 0.62 

Endocr 0.62 

Dermal 0.62 

Ocular 0.62 

Bd Wt 0.62 

Immuno/ Lymphoret 

26 Rat 

(Wistar) 

52 wk 

(F) 0.3 M (reduction in serum 

immunoglobulins IgG1, 

IgG2a, IgG2C, IgA, and 

increase in IgM) 

Tennekes et al. 1989b 

TPT 

27 Rat 

(Wistar) 

104 wk 

(F) 6.2 F Tennekes et al. 1989b 

TPT 

28 Mouse 

(Hybrid) 

80 wk 

(F) 15.24 (decreased levels of 

serum immunoglobulins) 

Tennekes et al. 1989a 

TPT 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
236

0.3

239

1.6

240

5.2

241

15.24

76 

Table 3-5 Levels of Significant Exposure to Triphenyltins - Oral	 (continued) 

a Key to Species 

Figure (Strain) 

Reproductive 

29 Rat 

(Wistar) 

Cancer 

30 Rat 

(Wistar) 

31	 Rat 

(Wistar) 

32	 Mouse 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference 

Chemical Form 

104 wk 

(F) 0.3 M (Leydig cell hypertrophy 

and tubular atrophy) 

Tennekes et al. 1989b 

TPT 

104 wk 

(F) 

104 wk 

(F) 

80 wk 

ad libitum 

(F) 

1.6 CEL (pituitary tumors) 

5.2 F CEL (testicular tumors) 

15.24 F CEL (hepatocellular 

carcinoma) 

Tennekes et al. 1989b 

TPT 

Tennekes et al. 1989b 

TPT 

Tennekes et al. 1989a 

TPT 

a The number corresponds to entries in Figure 3-5. 

Bd Wt = body weight; Cardio = cardiovascular; CEL = cancer effect level; d = day(s); Endocr = endocrine; (F) = feed; F = Female; Gastro = gastrointestinal; Gd = gestational day; 

(GO) = gavage in oil; (GW) = gavage in water; hemato = hematological; Immuno = immunological; LOAEL = lowest-observed-adverse-effect level; M = male; NOAEL = 

no-observed-adverse-effect level; Resp = respiratory; x = time(s); wk = week(s) 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
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U U U U

U U U

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S3LJ K5DEELW V+DPVWHU 12$(/$QLPDOV 12$(/+XPDQV RWKHUWKDQ

T&RZ D6KHHS J*XLQHD3LJ &DQFHU

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
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F&DW +XPDQV I)HUUHW Q0LQN &DQFHU(IIHFW/HYHO$QLPDOV &DQFHU(IIHFW/HYHO+XPDQV /'/&

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U5DW P0RXVH H*HUELO /2$(//HVV6HULRXV$QLPDOV /2$(//HVV6HULRXV+XPDQV IRUHIIHFWV

S3LJ K5DEELW V+DPVWHU 12$(/$QLPDOV 12$(/+XPDQV RWKHUWKDQ

T&RZ D6KHHS J*XLQHD3LJ &DQFHU

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
'HDWK

5HVSLUDWRU\&DUGLRYDVFXODU*DVWURLQWHVWLQDO+HP0XVFXORVNHOHWDO+HSDWL5HQDO(QGRFULQH'HUP2FXODU%RG\,P5HSURGXFWLYH&DQFHU


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79 

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P P P P P P P P P

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'RVHVUHSUHVHQWWKHORZHVWGRVHWHVWHGSHUVWXG\WKDWSURGXFHGDWXPRULJHQLF

 UHVSRQVHDQGGRQRWLPSO\WKHH[LVWHQFHRIDWKUHVKROGIRUWKHFDQFHUHQGSRLQW

F&DW +XPDQV I)HUUHW Q0LQN &DQFHU(IIHFW/HYHO$QLPDOV &DQFHU(IIHFW/HYHO+XPDQV /'/&

G'RJ N0RQNH\ M3LJHRQ R2WKHU /2$(/0RUH6HULRXV$QLPDOV /2$(/0RUH6HULRXV+XPDQV 0LQLPDO5LVN /HYHO

U5DW P0RXVH H*HUELO /2$(//HVV6HULRXV$QLPDOV /2$(//HVV6HULRXV+XPDQV IRUHIIHFWV

S3LJ K5DEELW V+DPVWHU 12$(/$QLPDOV 12$(/+XPDQV RWKHUWKDQ

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TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
2126

6.7

2119

3

2128

0.7 2

2120

1

3

2109

0.5

2095

3

2117

2

80 

Table 3-6 Levels of Significant Exposure to Triethyltins - Oral 

a Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) 

ACUTE EXPOSURE 

Death 

1 Rat 

(Wistar) 

2 wk 

ad libitum 

(F) 

System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

6.7 M (3/10 died, none in 

controls) 

Reference 

Chemical Form 

Snoeij et al. 1985 

TET 

2 Rat 

(CD) 

2 wk 

2 x/wk 

(GW) 

3 M (4/10 rats died after third 

dose) 

Squibb et al. 1980 

TET 

Systemic 

3 Rat 

(Wistar) 

2 wk 

ad libitum 

(F) 

Bd Wt 0.7 M (13% reduction in final 

body weight) 

2 M (30% reduction in final 

body weight) 

Snoeij et al. 1985 

TET 

4 Rat 

(CD) 

2 wk 

2 x/wk 

(GW) 

Bd Wt 1 M 3 M (significant body weight 

loss) 

Squibb et al. 1980 

TET 

5 Rat 

(SpragueDawley) 

Neurological 

6 Rat 

(SpragueDawley) 

6 d 

1 x/d 

(GO) 

once 

(GW) 

Bd Wt 

3 M (significant disruption of 

normal spontaneous 

activity) 

0.5 M (body weight loss) Yallapragada et al. 1991 

TET 

Kernan et al. 1991 

TET 

7 Rat 

(albino) 

2 wk 

ad libitum 

(F) 

2 (ataxia, paralysis of hind 

limbs) 

Magee et al. 1957 

TET 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
2127

2 6.7

2118

1

2108

1 1.5

2116

2

177

1.4

2090

0.66

125

0.8

81 

Table 3-6 Levels of Significant Exposure to Triethyltins - Oral (continued) 

a Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference 

Chemical Form 

8 Rat 

(Wistar) 

2 wk 

ad libitum 

(F) 

2 M 6.7 M (brain edema) Snoeij et al. 1985 

TET 

9 Rat 

(CD) 

2 wk 

2 x/wk 

(GW) 

1 M (reduced grip strength 

and startle 

responsiveness) 

Squibb et al. 1980 

TET 

10 Rat 

(SpragueDawley) 

6 d 

1 x/d 

(GO) 

INTERMEDIATE EXPOSURE 

Death 

11 Rat 

(albino) 

3 wk 

ad libitum 

(F) 

1 M 1.5 M (hind limb paralysis) 

2 (4/6 rats died during the 

third week) 

Yallapragada et al. 1991 

TET 

Magee et al. 1957 

TET 

12 Rat 

(Wistar) 

Systemic 

13 Rat 

(SpragueDawley) 

11 wk 

(W) 

90 d 

ad libitum 

(W) 

Bd Wt 0.66 M 

1.4 (death) Smith 1973 

TET 

Purves et al. 1991 

TET 

14 Rat 

(CD) 

4 wk 

(W) Bd Wt 0.8 M (50% decrease in body 

weight) 

Reiter et al. 1980 

TET 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
2164

0.7

199

2.8

2089

0.26

0.66

197

0.4

0.8

198

4.2

82 

Table 3-6 Levels of Significant Exposure to Triethyltins - Oral (continued) 

a Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

LOAEL 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

Serious 

(mg/kg/day) 

Reference 

Chemical Form 

Neurological 

15 Rat 

(SpragueDawley) 

3 mo 

ad libitum 

(W) 

Eto et al. 1971 

TET 

0.7 (brain edema; changes in 

brain lipid composition) 

16 Rat 

(OsborneMendel) 

22 d 

ad libitum 

(W) 

Graham and Gonatas 1973 

TET 

2.8 (motor dysfunction, 

splitting of peripheral 

myelin sheaths and 

edema of brain) 

17 Rat 

(SpragueDawley) 

90 d 

ad libitum 

(W) 

Purves et al. 1991 

TET 

0.26 M 0.66 M (significant increase in 

brain spongiosis) 

18 Rat 

(CD) 

4 wk 

ad libitum 

(W) 

Reiter et al 1980 

TET 

0.4 M (diminished maze activity 

and startle response) 

0.8 M (paralysis) 

19 Rat 

(Long- Evans) 

3 wk 

ad libitum 

(W) 

Richman and Bienkamper 

1984 

TET 

4.2 M (hind limb paralysis 

followed by recovery; 

demyelination in spinal 

cord and peripheral 

nerves) 

a The number corresponds to entries in Figure 3-6. 

Bd Wt = body weight; d = day(s); (F) = feed; (GO) = gavage in oil; (GW) = gavage in water; LOAEL = lowest-observed-adverse-effect level; M = male; mo = month(s); NOAEL = 

no-observed-adverse-effect; x = time(s); (W) = drinking water; wk = week(s) 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
Death 

Body WNeurological 

eight 

Figure 3-6 Levels of Significant Exposure to Triethyltins - Oral 

Acute (≤14 days) 

Systemic mg/kg/day 

10 

1r 8r 

2r 4r 6r 

3r 7r 8r 

10r 

1 4r 9r 10r 

3r 

5r 

0.1 

c-Cat 

d-Dog

r-Rat 

p-Pig

q-Cow

 -Humans 

k-Monkey

m-Mouse 

h-Rabbit 

a-Sheep 

f-Ferret 

j-Pigeon

e-Gerbil 

s-Hamster 

g-Guinea Pig 

n-Mink 

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

LOAEL, Less Serious-Animals

 NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

LOAEL, Less Serious-Humans

 NOAEL - Humans

 LD50/LC50

Minimal Risk Level

 for effects

 other than

 Cancer 

TIN AND TIN COMPOUNDS 83 

3. HEALTH EFFECTS 
Death 

Body WNeurological 

eight 

Figure 3-6 Levels of Significant Exposure to Triethyltins - Oral (Comtinued) 

Intermediate (15-364 days) 

Systemic mg/kg/day 

10 

19r 

16r 

11r 

12r
 

1
 

14r 18r 

15r 13r 17r 

18r 

17r 

0.1 

c-Cat 

d-Dog

r-Rat 

p-Pig

q-Cow

 -Humans 

k-Monkey

m-Mouse 

h-Rabbit 

a-Sheep 

f-Ferret 

j-Pigeon

e-Gerbil 

s-Hamster 

g-Guinea Pig 

n-Mink 

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

LOAEL, Less Serious-Animals

 NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

LOAEL, Less Serious-Humans

 NOAEL - Humans

 LD50/LC50

Minimal Risk Level

 for effects

 other than

 Cancer 

TIN AND TIN COMPOUNDS 84 

3. HEALTH EFFECTS 
2105

7

2123

5

150

12.6

2124

2

2143

4

2141

3.75

2145

3

85 

Table 3-7 Levels of Significant Exposure to Trimethyltins - Oral 

a Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) 

ACUTE EXPOSURE 

Death 

1 Rat 

(albino) 

once 

(GO) 

System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

7 M (4 out 10 rats died) 

Reference 

Chemical Form 

Alessandri et al. 1994 

TMT 

2 Rat 

(Long- Evans) 

once 

(G) 5 (fatal seizures after 4 

doses) 

Bouldin et al. 1981 

TMT 

3 Rat 

(Wistar) 

once 

(GO) 12.6 M (LD50) Brown et al. 1979 

TMT 

4 Rat 

(Wistar) 

2 wk 

ad libitum 

(F) 

2 M (2/10 deaths, none in 

controls) 

Snoeij et al. 1985 

TMT 

5 Hamster 

(NS) 

once 

(GO) 

4 F (death within 4 days of 

dosing) 

Brown et al. 1984 

TMT 

6 Primate 

(NS) 

once 

(GO) 3.75 M (4/11 died within 3 days 

of dosing) 

Brown et al. 1984 

TMT 

7 Gerbil 

(NS) 

once 

(GO) 3 F (death within 2-7 days of 

dosing) 

Brown et al. 1984 

TMT 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
2140

4

151

3 10

2177

12.25

12.25

2107

1.5

2.5

2122

1

2243

6

86 

Table 3-7 Levels of Significant Exposure to Trimethyltins - Oral (continued) 

a Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

LOAEL 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

Serious 

(mg/kg/day) 

Reference 

Chemical Form 

8 Gerbil 

(Mongolian) 

once 

(GO) 

Nolan et al. 1990 

TMT 

4 (death within days of 

dosing) 

Systemic 

9 Rat 

(Wistar) 

once 

(GO) Renal Opacka and Sparrow 1985 

TMT 

3 M (slightly dilated proximal 

tubules and impaired 

organ function) 

10 M (marked proximal tubule 

necrosis, impaired organ 

function) 

10 Rat 

(Long- Evans) 

once 

(GW) Renal Robertson et al. 1987 

TMT 

12.25 M (severe kidney tubule 

damage) 

Bd Wt 12.25 M (significant weight loss) 

11 Rat 

(SpragueDawley) 

6 d 

1 x/d 

(GO) 

Bd Wt Yallapragada et al. 1991 

TMT 

1.5 M (reduced body weight 

gain) 

2.5 M (body weight loss) 

Neurological 

12 Rat 

(Long- Evans) 

14 d 

1 x/d 

(G) 

Bouldin et al. 1981 

TMT 

1 (self-mutilating and highly 

aggressive behavior) 

13 Rat 

(Long- Evans) 

once 

(G) Chang and Dyer 1983 

TMT 

6 M (morphological damage 

to sensory neurons) 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
161

7.5

2093

9

2094

8

2099

9

2125

0.7

2

2100

9

87 

Table 3-7 Levels of Significant Exposure to Trimethyltins - Oral (continued) 

a Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference 

Chemical Form 

14 Rat 

(Long- Evans) 

once 

(GW) Chang et al 1983 

TMT 

7.5 M (neuronal damage; 

mainly olfactory cortex, 

fascia dentata) 

15 Rat 

(SpragueDawley) 

once 

(GW) 

Ishida et al. 1997 

TMT 

9 M (progressive 

degeneration of 

hippocampal cells; 

impaired learning) 

16 Rat 

(Long- Evans) 

once 

(GW) 

Kutscher 1992 

TMT 

8 F (significant damage to 

hippocampal structures) 

17 Rat 

(SpragueDawley) 

once 

(G) 

Nishimura et al. 2001 

TMT 

9 M (aggressive behavior and 

biochemical changes in 

brain areas) 

18 Rat 

(Wistar) 

2 wk 

ad libitum 

(F) 

0.7 M Snoeij et al. 1985 

TMT 

2 M (neuronal degeneration 

in hippocampus and 

pyriform cortex) 

19 Rat 

(SpragueDawley) 

once 

(GW) 

Tsutsumi et al. 2002 

TMT 

9 M (loss of pyramidal cells in 

hippocampus and 

impaired learning) 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
2106

0.75

169

3

2144

4

2142

3

2146

3

2139

3.5

88 

Table 3-7 Levels of Significant Exposure to Trimethyltins - Oral (continued) 

a Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference 

Chemical Form 

20 Rat 

(SpragueDawley) 

6 d 

1 x/d 

(GO) 

0.75 M (hyperexcitability; 

reduced brain calmodulin 

activity) 

Yallapragada et al. 1991 

TMT 

21 Mouse 

(BALB/c) 

once 

(GW) 3 M (neuronal damage; 

mainly hippocampal, 

fascia dentata) 

Chang et al 1983 

TMT 

22 Hamster 

(NS) 

once 

(GO) 

4 F (whole body tremors) Brown et al. 1984 

TMT 

23 Primate 

(NS) 

once 

(GO) 3 M (ataxia; neuronal 

degeneration in brain 

areas) 

Brown et al. 1984 

TMT 

24 Gerbil 

(NS) 

once 

(GO) 3 F (tremors, prostration, 

hippocampal 

degeneration) 

Brown et al. 1984 

TMT 

25 Gerbil 

(Mongolian) 

once 

(GO) 3.5 (prostration, tremors and 

ataxia; histopathological 

changes in the CNS) 

Nolan et al. 1990 

TMT 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
2092

0.8

2091

0.8

2121

1

2147

0.05

89 

Table 3-7 Levels of Significant Exposure to Trimethyltins - Oral (continued) 

a Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) 

INTERMEDIATE EXPOSURE 

Systemic 

26 Rat 

(Wistar) 

25 d 

ad libitum 

(F) 

System 

Bd Wt 

NOAEL 

(mg/kg/day) 

0.8 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference 

Chemical Form 

Allen et al. 1994 

TMT 

Neurological 

27 Rat 

(Wistar) 

25 d 

ad libitum 

(F) 

0.8 (aggressive behavior; cell 

necrosis in the 

hippocampus, pyriform 

cortex, amygdala, and 

olfactory tuberculum) 

Allen et al. 1994 

TMT 

28 Rat 

(Long- Evans) 

26 d 

1 x/2d 

(G) 

1 (tremors and seizures in 

pups; neuronal necrosis 

in hippocampus) 

Bouldin et al. 1981 

TMT 

Developmental 

29 Rat 

(SpragueDawley) 

56 d 

ad libitum 

(W) 

0.05 M (significant decrease in 

extinction learning ability) 

Noland et al. 1982 

TMT 

a The number corresponds to entries in Figure 3-7. 

Bd Wt = body weight; d = day(s); (F) = feed; F = Female; (G) = gavage; (GO) = gavage in oil; (GW) = gavage in water; LD50 = lethal dose, 50% kill; LOAEL = 

lowest-observed-adverse-effect level; M = male; NOAEL = no-observed-adverse-effect level; x = time(s); (W) = drinking water; wk = week(s) 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
Death 

Renal Body WNeurological 

eight 

Figure 3-7 Levels of Significant Exposure to Trimethyltins - Oral 

Acute (≤14 days) 

mg/kg/day Systemic 

100 

3r 10r 10r
 

10
 9r 15r 17r 19r

16r 14r 1r 

13r 

2r 

5s 8e 22s 6c 25e 

7e 9r 23c 21m 24e 

11r 

4r 18r 

11r 

1 12r 

20r 18r 

0.1 

c-Cat 

d-Dog

r-Rat 

p-Pig

q-Cow

 -Humans 

k-Monkey

m-Mouse 

h-Rabbit 

a-Sheep 

f-Ferret 

j-Pigeon

e-Gerbil 

s-Hamster 

g-Guinea Pig 

n-Mink 

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

LOAEL, Less Serious-Animals

 NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

LOAEL, Less Serious-Humans

 NOAEL - Humans

 LD50/LC50

Minimal Risk Level

 for effects

 other than

 Cancer 

TIN AND TIN COMPOUNDS 90 

3. HEALTH EFFECTS 
Body W

Neurological 

Developmental 

eight 

Figure 3-7 Levels of Significant Exposure to Trimethyltins - Oral (Continued) 

Intermediate (15-364 days) 

mg/kg/day Systemic 

10 

1 28r 

26r 27r 

0.1 

29r 

0.01 

c-Cat 

d-Dog

r-Rat 

p-Pig

q-Cow

 -Humans 

k-Monkey

m-Mouse 

h-Rabbit 

a-Sheep 

f-Ferret 

j-Pigeon

e-Gerbil 

s-Hamster 

g-Guinea Pig 

n-Mink 

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

LOAEL, Less Serious-Animals

 NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

LOAEL, Less Serious-Humans

 NOAEL - Humans

 LD50/LC50

Minimal Risk Level

 for effects

 other than

 Cancer 

TIN AND TIN COMPOUNDS 91 

3. HEALTH EFFECTS 
2234

37.5

145

148

146

194

2112

27

2062

149.6

2213

0.25

2.5

2.5

10

2022

5

10

92 

Table 3-8 Levels of Significant Exposure to Tributyltins - Oral 

a Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) 

ACUTE EXPOSURE 

Death 

1 Rat 

(SpragueDawley) 

3 d 

1 x/d 

(GO) 

System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

37.5 M (6/50 died) 

Reference 

Chemical Form 

Elsabbagh et al. 2002 

TBT 

2 Rat 

(albino) 

once 

(GO) 148 M (LD50 in corn oil) Elsea and Paynter 1958 

TBT 

3 Rat 

(albino) 

once 

(GW) 194 M (LD50 in aqueous 

suspension) 

Elsea and Paynter 1958 

TBT 

4 Mouse 

(Hybrid) 

Gd 6-17 

1 x/d 

(GO) 

27 F (3/40 pregnant mice died, 

none in controls) 

Faqi et al. 1997 

TBT 

5 Hamster 

(Golden 

Syrian) 

once 

(GO) 149.6 M (2-week LD50; 172 

mg/kg in females) 

Takagi et al. 1992 

TBT 

Systemic 

6 Rat 

(SpragueDawley) 

11 d 

Gd 8-19 

1 x/day 

(GO) 

Endocr 0.25 F 2.5 F (reduced serum 

thyroxine) 

Adeeko et al. 2003 

TBT 

Bd Wt 2.5 F 10 F (18% reduced body 

weight gain) 

7 Rat 

(Long- Evans) 

Gd 6-20 

1 x/d 

(GO) 

Bd Wt 5 F 10 F (20% decrease in body 

weight gain) 

Crofton et al. 1989 

TBT 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
2032

60

30

2227

58.6

2050

1.5 2.5

2017

5

2020

20

2241

39 58.6

2225

58.6

2220

117.2

93 

Table 3-8 Levels of Significant Exposure to Tributyltins - Oral	 (continued) 

a Key to 

Figure 

8 

9 

10 

11 

12 

13 

14 

15 

Species 

(Strain) 

Rat 

(Wistar) 

Rat 

(Wistar) 

Rat 

(SpragueDawley) 

Mouse 

(albino) 

Mouse 

(albino) 

Mouse 

(albino) 

Mouse 

(albino) 

Gn Pig 

(Hartley) 

Exposure/ 

Duration/ 

Frequency 

(Route) 

once 

(GO) 

once 

(GO) 

6 d 

1 x/d 

(GO) 

Gd 6-15 

(GO) 

Gd 6-15 

(GO) 

once 

(GO) 

once 

(GO) 

once 

(GO) 

System 

Endocr
 

Bd Wt
 

Hepatic 

Bd Wt 

Bd Wt 

Hemato 

Hepatic 

Hepatic 

Hepatic 

NOAEL 

(mg/kg/day) 

60 M 

1.5 M 

20 F 

39 M 

117.2 M 

Less Serious 

(mg/kg/day) 

58.6 M (increased serum AST 

and ALT activities) 

5 F	 (18% reduction in body 

weight gain) 

58.6 M (liver damage) 

LOAEL 

Serious 

(mg/kg/day) 

30 M (body weight loss 48 

hours 

after dosing) 

2.5 M (significant weight loss) 

58.6 M (liver necrosis) 

Reference 

Chemical Form 

Raffray and Cohen 1993 

TBT 

Ueno et al. 2003b 

TBT 

Yallapragada et al. 1991 

TBT 

Baroncelli et al. 1995 

TBT 

Karrer et al. 1995 

TBT 

Ueno et al. 1995 

TBT 

Ueno et al. 2003b 

TBT 

Ueno et al. 2003a 

TBT 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
2229

58.6

2063

29.6

66.7

100

2031

30

2175

1.25

2.5

2033

2.5

5

2131

2

6.7

94 

Table 3-8 Levels of Significant Exposure to Tributyltins - Oral (continued) 

a Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference 

Chemical Form 

16 Gn Pig 

(Hartley) 

once 

(GO) Hepatic 58.6 M Ueno et al. 2003b 

TBT 

17 Hamster 

(Golden 

Syrian) 

once 

(GO) Hepatic 29.6 (bile duct dilation and 

inflammatory damage) 

Takagi et al. 1992 

TBT 

Bd Wt 66.7 F 100 F (13% decrease in final 

body weight) 

Immuno/ Lymphoret 

18 Rat 

(Wistar) 

once 

(GO) 30 M (significant decrease in 

relative and absolute 

thymus weight) 

Raffray and Cohen 1993 

TBT 

19 Rat 

(Fischer- 344) 

10 d 

1 x/d 

(GO) 

1.25 M 2.5 M (enhanced primary 

immune response to 

SRBC; significant 

decrease in thymus 

weight) 

Smialowicz et al. 1989 

TBT 

20 Rat 

(Fischer- 344) 

10 d 

1 x/d 

(GO) 

2.5 M 5 M (enhanced immune 

response to SRBC 

immunization; reduced T 

cells) 

Smialowicz et al. 1990 

TBT 

21 Rat 

(Wistar) 

2 wk 

ad libitum 

(F) 

2 M 6.7 M (lymphocyte depletion in 

the thymus) 

Snoeij et al. 1985 

TBT 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
2233

37.5

2046

6.3

2049

1.5

2.5

2214

10

2054

25

2055

100

95 

Table 3-8 Levels of Significant Exposure to Tributyltins - Oral (continued) 

a Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference 

Chemical Form 

Neurological 

22 Rat 

(SpragueDawley) 

3 d 

1 x/d 

(GO) 

37.5 M (agressive behavior; 

seizures) 

Elsabbagh et al. 2002 

TBT 

23 Rat 

(Wistar) 

once 

(G) 6.3 M (decreased dark-phase 

spontaneous motor 

activity) 

Ema et al. 1991a 

TBT 

24 Rat 

(SpragueDawley) 

6 d 

1 x/d 

(GO) 

1.5 M 2.5 M (slight tremors and 

weakness) 

Yallapragada et al. 1991 

TBT 

Reproductive 

25 Rat 

(SpragueDawley) 

11 d 

Gd 8-19 

1 x/day 

(GO) 

10 F Adeeko et al. 2003 

TBT 

26 Rat 

(Wistar) 

3 d 

Gd 7-9 

Gd 10-12 

Gd 13-15 

(GO) 

25 F (significant increase in 

resorptions and 

post-implantation loss) 

Ema et al. 1995 

TBT 

27 Rat 

(Wistar) 

Gd 9 

once 

(GO) 

100 F (significant increase in 

post-implantation loss) 

Ema et al. 1997a 

TBT 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
2057

8.1

16.3

2060

8

16

2235

5

10

2236

5 10

2016

5

176

23.4

35

96 

Table 3-8 Levels of Significant Exposure to Tributyltins - Oral (continued) 

a Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference 

Chemical Form 

28 Rat 

(Wistar) 

4 d 

Gd 0-3 

(GO) 

8.1 F 16.3 F (significant increase in 

pregnancy failure) 

Harazono et al. 1998 

TBT 

29 Rat 

(Wistar) 

11 d 

Gd 7-17 

(GO) 

8 F 16 F (increased fetal deaths 

and resorptions) 

Noda et al. 1991a 

TBT 

30 Rat 

(SpragueDawley) 

10 d 

1 x/d 

(GO) 

5 M 10 M (histologic alterations of 

seminal vesicles and 

epididymis) 

Yu et al. 2003a 

TBT 

31 Rat 

(SpragueDawley) 

10 d 

1 x/d 

(GO) 

5 M 10 M (reduced sperm counts) Yu et al. 2003b 

TBT 

32 Mouse 

(albino) 

Gd 6-15 

(GO) 5 F (increased early 

parturitions 

and number of 

resorptions) 

Baroncelli et al. 1995 

TBT 

33 Mouse 

(albino) 

10 d 

Gd 6-15 

1x/d 

(GO) 

23.4 F 35 F (decreased number of 

implantations 

and living fetuses) 

Davis et al 1987 

TBT 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
2110

27

2215

10

2021

5 10

2053

25

2056

100

2052

1

2058

8.1

16.3

97 

Table 3-8 Levels of Significant Exposure to Tributyltins - Oral (continued) 

a Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference 

Chemical Form 

34 Mouse 

(Hybrid) 

Gd 6-17 

1 x/d 

(GO) 

Developmental 

35 Rat 

(SpragueDawley) 

11 d 

Gd 8-19 

1 x/day 

(GO) 

27 F 

10 

Faqi et al. 1997 

TBT 

Adeeko et al. 2003 

TBT 

36 Rat 

(Long- Evans) 

Gd 6-20 

1 x/d 

(GO) 

5 F Crofton et al. 1989 

TBT 

10 F (decreased pup survival) 

37 Rat 

(Wistar) 

3 d 

Gd 7-9 

Gd 10-12 

Gd 13-15 

(GO) 

Ema et al. 1995 

TBT 

25 (significant increase in 

incidence of clef palate 

when TBTC was given 

on Gd 13-15) 

38 Rat 

(Wistar) 

Gd 9 

once 

(GO) 

Ema et al. 1997a 

TBT 

100 (significant increase in 

incidence of cleft palate) 

39 Rat 

(SpragueDawley) 

Gd 6-20 

1 x/d 

(G) 

Gardlung et al. 1991 

TBT 

1 (hyperactivity and 

impaired learning) 

40 Rat 

(Wistar) 

4 d 

Gd 0-3 

(GO) 

8.1 16.3 (significantly reduced 

fetal weight) 

Harazono et al. 1998 

TBT 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
2059

8

16

2012

20

40

2015

10

20

174

11.7

2111

13.5

27

2051

8

98 

Table 3-8 Levels of Significant Exposure to Tributyltins - Oral (continued) 

a Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference 

Chemical Form 

41 Rat 

(Wistar) 

11 d 

Gd 7-17 

(GO) 

8 16 (significant increase in 

cleft palate incidence) 

Noda et al. 1991a 

TBT 

42 Mouse 

(albino) 

Gd 6-15 

1 x/d 

(GO) 

20 F 40 F (approximately 21% 

lower fetal weight) 

Baroncelli et al. 1990 

TBT 

43 Mouse 

(albino) 

Gd 6-15 

(GO) 10 F 20 F (significant increase in 

postnatal mortality) 

Baroncelli et al. 1995 

TBT 

44 Mouse 

(albino) 

10 d 

Gd 6-15 

1x/d 

(GO) 

11.7 F (cleft plate and other 

bone abnormalities) 

Davis et al 1987 

TBT 

45 Mouse 

(Hybrid) 

Gd 6-17 

1 x/d 

(GO) 

INTERMEDIATE EXPOSURE 

Death 

46 Rat 

(Wistar) 

5 wk 

3 d/wk 

(GW) 

13.5 27 

8 

(significant increased 

incidence of cleft palate) 

(unspecified number of 

deaths on week 3) 

Faqi et al. 1997 

TBT 

Attahiru et al. 1991 

TBT 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
2009

0.16

0.16

121

3

6

3

6

2207

2.5

10

20

2037

2.5

2.5

99 

Table 3-8 Levels of Significant Exposure to Tributyltins - Oral (continued) 

a Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference 

Chemical Form 

Systemic 

47 Monkey 

(Cynomolgus) 

22 wk 

6 d/wk 

(GW) 

Hemato 0.16 M Karrer et al. 1992 

TBT 

Bd Wt 0.16 M 

48 Rat 

(SpragueDawley) 

26 wk 

5 x/wk 

(GO) 

Endocr 3 M 6 M (33% increase in adrenal 

relative weight and 26% 

of the hypophysis) 

Funahashi et al. 1980 

TBT 

Bd Wt 3 M 6 M (13% decrease in final 

body weight) 

49 Rat 

(SpragueDawley) 

19 d 

Gd 0-19 

1 x/day 

(GO) 

Endocr 2.5 F 10 F (decreased serum T4 

and T3) 

Adeeko et al. 2003 

TBT 

Bd Wt 20 F (25% reduced weight 

gain) 

50 Rat 

(Wistar) 

30 d 

ad libitum 

(F) 

Hepatic 2.5 M Bressa et al. 1991 

TBT 

Renal 2.5 M 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
2043

16

16

127

1

4

128

0.25 4

1

4 16

1

4

16

120

4

100 

Table 3-8 Levels of Significant Exposure to Tributyltins - Oral (continued) 

a Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference 

Chemical Form 

51 Rat 

(Fischer- 344) 

6 wk 

ad libitum 

(F) 

Hepatic 16 (cholangitis with biliary 

retention) 

Carthew et al. 1992 

TBT 

Bd Wt 16 M (27% reduced final body 

weight relative to 

controls) 

52 Rat 

(Wistar) 

6 wk 

7 d/wk 

(F) 

Endocr 1 M (decreased serum insulin 

levels) 

4 M (decreased thyroxine, 

thyroid stimulating 

hormone and insulin; 

increased leutinizing 

hormone) 

Krajnc et al 1984 

TBT 

53 Rat 

(Wistar) 

4 wk 

ad libitum 

(F) 

Hemato 0.25 (decreased mean 

corpuscular volume, 

eosinophils) 

4 (abnormalities in all 

hematological 

components) 

Krajnc et al 1984 

TBT 

Hepatic 1 4 (slight atrophy of 

hematocytes) 

16 (liver necrosis and bile 

duct hyperplasia) 

Bd Wt 1 4 (10% lower final body 

weight) 

16 (weight loss) 

54 Rat 

(Wistar) 

6 wk 

ad libitum 

(F) 

Bd Wt 4 M Van Loveren et al 1990 

TBT 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
2039

8

2030

5

5

2088

25

2034

0.5

2042

16

181

3

101 

Table 3-8 Levels of Significant Exposure to Tributyltins - Oral (continued) 

a Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference 

Chemical Form 

55 Rat 

(Wistar) 

6 wk 

ad libitum 

(F) 

Bd Wt 8 M Vandebriel et al. 1998 

TBT 

56 Rat 

(SpragueDawley) 

28 d 

ad libitum 

(F) 

Hemato 

Hepatic 

5 

5 

Verdier et al. 1991 

TBT 

57 Mouse 

(BALB/c) 

Immuno/ Lymphoret 

58 Rat 

(Wistar) 

30 d 

ad libitum 

(F) 

30 d 

ad libitum 

(F) 

Bd Wt 25 M 

0.5 M (partial atrophy of 

mesenteric lymph nodes) 

Konno et al. 2001 

TBT 

Bressa et al. 1991 

TBT 

59 Rat 

(Fischer- 344) 

6 wk 

ad libitum 

(F) 

16 (22-28% reduced relative 

thymus weight) 

Carthew et al. 1992 

TBT 

60 Rat 

(SpragueDawley) 

26 wk 

5x/wk 

(GO) 

3 M (30% decreased relative 

thymus weight) 

Funahashi et al. 1980 

TBT 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
185

0.25

1 4

2176

5

10

187

1

2038

2

8

2029

0.5

5

2007

0.025

0.25

102 

Table 3-8 Levels of Significant Exposure to Tributyltins - Oral (continued) 

a Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

LOAEL 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

Serious 

(mg/kg/day) 

Reference 

Chemical Form 

61 Rat 

(Wistar) 

4 wk 

7 d/wk 

(F) 

Krajnc et al 1984 

TBT 

0.25 1 (17% decrease thymus 

weight) 

4 (35% decreased thymus 

weight) 

62 Rat 

(Fischer- 344) 

3 wk 

3 x/wk 

(GO) 

Smialowicz et al. 1989 

TBT 

5 M (significant reduction in 

thymus weight; reduced 

lymphoproliferative 

response to mitogen Con 

A). 

10 M (approximately 45% 

reduction 

in thymus weight) 

63 Rat 

(Wistar) 

6 wk 

ad libitum 

(F) 

Van Loveren et al 1990 

TBT 

1 M (reduced natural killer 

cell activity) 

64 Rat 

(Wistar) 

6 wk 

ad libitum 

(F) 

Vandebriel et al. 1998 

TBT 

2 M 8 M (25% reduced thymus 

weight) 

65 Rat 

(SpragueDawley) 

28 d 

ad libitum 

(F) 

Verdier et al. 1991 

TBT 

0.5 5 (slight impairment in host 

resistance to Listeria 

monocytogenes) 

66 Rat 

(Wistar) 

4.5-6 mo 

ad libitum 

(F) 

Vos et al. 1990 

TBT 

b

0.025 M 0.25 M (altered parameters of 

both specific and 

nonspecific 

immunocompetence) 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
2208

10

20

2024

10

2026

10

2113

2 10

2209

0.25

2237

0.025

0.25

103 

Table 3-8 Levels of Significant Exposure to Tributyltins - Oral	 (continued) 

a Key to Species 

Figure (Strain) 

Reproductive 

67 Rat 

(SpragueDawley) 

68	 Rat 

(Wistar) 

69	 Rat 

(Wistar) 

70	 Mouse 

(ICR) 

Developmental 

71 Rat 

(SpragueDawley) 

72	 Rat 

(SpragueDawley) 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference 

Chemical Form 

19 d 

Gd 0-19 

1 x/day 

(GO) 

10 20 (post-implantation loss; 

decreased litter size) 

Adeeko et al. 2003 

TBT 

42 d 

Gd 1-21 

Ld 1-21 

(F) 

10 F Ogata et al. 2001 

TBT 

42 d 

Gd 1-21 

Ld 1-21 

(F) 

10 M Omura et al. 2001 

TBT 

4 wk 

2 x/wk 

(GW) 

2 M 10 M (reduced sperm counts) Kamasaka et al. 2002 

TBT 

19 d 

Gd 0-19 

1 x/day 

(GO) 

0.25 M (increased anogenital 

distance) 

Adeeko et al. 2003 

TBT 

Gd 8-21 

Ld 1-21 

Pld 1-60 

(GO) 

0.025 0.25 (decreased pup's liver 

and thymus weight) 

Cooke et al. 2004 

TBT 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
2245

2

2244

2

2023

2

10

2025

0.4

2

2238

0.25

2.5

104 

Table 3-8 Levels of Significant Exposure to Tributyltins - Oral	 (continued) 

a Key to Species 

Figure (Strain) 

73	 Rat 

(Wistar) 

74	 Rat 

(Wistar) 

75	 Rat 

(Wistar) 

76	 Rat 

(Wistar) 

77	 Rat 

(SpragueDawley) 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference 

Chemical Form 

42 d 

Gd 1-21 

Ld 1-21 

(F) 

2 F (slight reduction in pup 

weight gain; reduced 

serum LH concentration) 

Makita et al. 2003 

TBT 

42 d 

Gd 1-21 

Ld 1-21 

(F) 

2 M (reduced postnatal 

weight gain and 

decreased prostate 

weight) 

Makita et al. 2004 

TBT 

42 d 

Gd 1-21 

Ld 1-21 

(F) 

2 F 10 F (alterations in 

developmental landmaks; 

reduced birth weight) 

Ogata et al. 2001 

TBT 

42 d 

Gd 1-21 

Ld 1-21 

(F) 

0.4 M 2 M (decreased pup weight in 

F1 generation on Pnd 14 

and 21) 

Omura et al. 2001 

TBT 

Gd 8-21 

Ld 1-21 

Pld 1-70 

(GO) 

0.25 2.5 (mild to moderate thymus 

atrophy) 

Tryphonas et al. 2004 

TBT 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
2005

2.5

2.5

2.5

0.25

2.1

2.5

0.25

2.1

0.19

2.1

0.19

2.1

0.19

2.1

2006

0.025

0.25

105 

Table 3-8 Levels of Significant Exposure to Tributyltins - Oral (continued) 

a Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) 

CHRONIC EXPOSURE 

Systemic 

78 Rat 

(Wistar) 

106 wk 

ad libitum 

(F) 

System 

Resp 

NOAEL 

(mg/kg/day) 

2.5 F 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference 

Chemical Form 

Wester et al. 1990 

TBT 

Cardio 2.5 F 

Gastro 2.5 F 

Hemato 0.25 F 2.1 M (decreased hemoglobin 

and hematocrit after 12 

months) 

Musc/skel 2.5 F 

Hepatic 0.25 F 2.1 M (29% increase in 

absolute liver weight; 

increased serum liver 

transaminases) 

Renal 0.19 M 2.1 M (29% increase in 

absolute kidney weight) 

Endocr 0.19 M 2.1 M (decreased thyroid 

follicular epithelial cell 

height) 

Bd Wt 0.19 M 2.1 M (decreased body weight 

from week 67 onward) 

Immuno/ Lymphoret 

79 Rat 

(Wistar) 

18 mo 

ad libitum 

(F) 

c 0.025 M 0.25 M (altered parameters of 

both specific and 

nonspecific 

immunocompetence) 

Vos et al. 1990 

TBT 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
2003

2.1

106 

Table 3-8 Levels of Significant Exposure to Tributyltins - Oral (continued) 

a Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference 

Chemical Form 

80 Rat 

(Wistar) 

106 wk 

ad libitum 

(F) 

2.1 M (significant changes in 

serum immunoglobulin 

levels) 

Wester et al. 1990 

TBT 

a The number corresponds to entries in Figure 3-8. 

b Used to derive an intermediate-duration minimal risk level (MRL) of 0.0003 mg/kg/day; The MRL was derived by dividing the NOAEL by an uncertainty factor of 100 (10 for animal 

to human extrapolation and 10 for human variability). 

c Used to derive a chronic-duration minimal risk level (MRL) of 0.0003 mg/kg/day; The MRL was derived by dividing the NOAEL by an uncertainty factor of 100 (10 for animal to 

human extrapolation and 10 for human variability). 

Bd Wt = body weight; d = day(s); Endocr = endocrine; (F) = feed; F = Female; (G) = gavage; Gastro = gastrointestinal; Gd = gestational day; (GO) = gavage in oil; (GW) = gavage in 

water hemato = hematological; LD50 = lethal dose, 50% kill; LOAEL = lowest-observed-adverse-effect level; M = male; mo = month(s); NOAEL = no-observed-adverse-effect level; 

Resp = respiratory; x = time(s); wk = week(s) 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
Death 

Hematological Hepatic Endocrine Body WImmuno/LNeurological Reproductive Developmental 

1000 

eight 

ymphor 

Figure 3-8 Levels of Significant Exposure to Tributyltins - Oral 

Acute (≤14 days) 

mg/kg/day Systemic 

3r 

5s 2r 

15g 100 17s 27r 38r 

17s 16g 13m 14m 9r 8r

1r 13m 22r 42m 33m

17s 8r 18r 4m 34m 26r 45m 37r 33m

12m 42m 43m 

28r 29r 40r

45m 44m

10 6r 7r 25r 30r 31r 43m 35r 36r 

28r 29r 40r

21r 23r 

11m 7r 20r 32m 30r 31r 36r 

6r 6r 10r 19r 20r 24r 

21r 

10r 24r 

19r 

1 39r 

6r 

0.1 

c-Cat 

d-Dog

r-Rat 

p-Pig

q-Cow

 -Humans 

k-Monkey

m-Mouse 

h-Rabbit 

a-Sheep 

f-Ferret 

j-Pigeon

e-Gerbil 

s-Hamster 

g-Guinea Pig 

n-Mink 

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

LOAEL, Less Serious-Animals

 NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

LOAEL, Less Serious-Humans

 NOAEL - Humans

 LD50/LC50

Minimal Risk Level

 for effects

 other than

 Cancer 

TIN AND TIN COMPOUNDS 107 

3. HEALTH EFFECTS 
Developmental 

Figure 3-8 Levels of Significant Exposure to Tributyltins - Oral (Continued) 

Acute (≤14 days) 

mg/kg/day 

1000 

100 

41r 

10 

41r 

1 

0.1 

c-Cat 

d-Dog

r-Rat 

p-Pig

q-Cow

 -Humans 

k-Monkey

m-Mouse 

h-Rabbit 

a-Sheep 

f-Ferret 

j-Pigeon

e-Gerbil 

s-Hamster 

g-Guinea Pig 

n-Mink 

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

LOAEL, Less Serious-Animals

 NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

LOAEL, Less Serious-Humans

 NOAEL - Humans

 LD50/LC50

Minimal Risk Level

 for effects

 other than

 Cancer 

TIN AND TIN COMPOUNDS 108 

3. HEALTH EFFECTS 
Death 

Hematological Hepatic Renal Endocrine Body WImmuno/LReproductive Developmental 

eight 

ymphor 

Figure 3-8 Levels of Significant Exposure to Tributyltins - Oral (Continued) 

Intermediate (15-364 days) 

Systemic

mg/kg/day 

100 

57m 49r 67r 51r 53r 51r 53r 59r 

10 49r 62r 70m 67r 68r 69r 75r 46r 55r 64r 

48r 48r 56r 56r 62r 65r 53r 53r 52r 53r 54r 61r 

48r 48r 60r 50r 50r 49r 64r 70m 73r 74r 75r 

1 53r 52r 53r 61r 63r 

58r 65r 76r 

53r 61r 66r 71r 72r 

47k 47k 

0.1 

66r 72r 

0.01 

0.001 

0.0001 

c-Cat 

d-Dog

r-Rat 

p-Pig

q-Cow

 -Humans 

k-Monkey

m-Mouse 

h-Rabbit 

a-Sheep 

f-Ferret 

j-Pigeon

e-Gerbil 

s-Hamster 

g-Guinea Pig 

n-Mink 

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

LOAEL, Less Serious-Animals

 NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

LOAEL, Less Serious-Humans

 NOAEL - Humans

 LD50/LC50

Minimal Risk Level

 for effects

 other than

 Cancer 

TIN AND TIN COMPOUNDS 109 

3. HEALTH EFFECTS 
Developmental 

Figure 3-8 Levels of Significant Exposure to Tributyltins - Oral (Continued) 

Intermediate (15-364 days) 

mg/kg/day 

100 

10 

77r 76r 

1 

77r 

0.1 

0.01 

0.001 

0.0001 

c-Cat 

d-Dog

r-Rat 

p-Pig

q-Cow

 -Humans 

k-Monkey

m-Mouse 

h-Rabbit 

a-Sheep 

f-Ferret 

j-Pigeon

e-Gerbil 

s-Hamster 

g-Guinea Pig 

n-Mink 

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

LOAEL, Less Serious-Animals

 NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

LOAEL, Less Serious-Humans

 NOAEL - Humans

 LD50/LC50

Minimal Risk Level

 for effects

 other than

 Cancer 

TIN AND TIN COMPOUNDS 110 

3. HEALTH EFFECTS 
Respiratory 

Cardiovascular Gastrointestinal Hematological Musculoskeletal Hepatic Renal Endocrine Body WImmuno/L

eight 

ymphor 

Figure 3-8 Levels of Significant Exposure to Tributyltins - Oral (Continued) 

Chronic (≥365 days) 

Systemic 

mg/kg/day 

10 

78r 78r 78r 78r 78r 78r 78r 78r 78r 80r 

1 

78r 78r 79r 

78r 78r 78r 

0.1 

79r 

0.01 

0.001 

0.0001 

c-Cat 

d-Dog

r-Rat 

p-Pig

q-Cow

 -Humans 

k-Monkey

m-Mouse 

h-Rabbit 

a-Sheep 

f-Ferret 

j-Pigeon

e-Gerbil 

s-Hamster 

g-Guinea Pig 

n-Mink 

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

LOAEL, Less Serious-Animals

 NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

LOAEL, Less Serious-Humans

 NOAEL - Humans

 LD50/LC50

Minimal Risk Level

 for effects

 other than

 Cancer 

TIN AND TIN COMPOUNDS 111 

3. HEALTH EFFECTS 
 

TIN AND TIN COMPOUNDS 112 

3. HEALTH EFFECTS 

dose producing death following a single gavage administration was 378 mg tin/kg as stannous chloride 

(NTP 1982). All mice survived the 14-day feeding of the compound up to dietary levels of 

2,457 mg/kg/day. These studies were performed in order to set doses for the chronic bioassay of stannous 

chloride in rats and mice (see Section 3.2.2.8). 

In intermediate-duration studies (4 or 13 weeks), rats were fed various inorganic tin compounds. A single 

female (1/10) died during week 11 with after receiving doses of 795 mg tin/kg/day as stannous chloride. 

A total of four males receiving doses of 315 mg/kg/day died during weeks 8 and 9 leading to 

discontinuation of this dose (De Groot et al. 1973). 

The results of the chronic bioassays showed somewhat lower survival of high-dose male rats (63 mg 

tin/kg/day as stannous chloride) compared to the controls. In mice, survival of control males was affected 

more than the dosed groups (82 and 164 mg tin/kg/day), but survival of the female dosed groups was 

affected less than the controls (NTP 1982). No explanation was provided for the apparent lower survival 

among control male mice. 

Reliable LOAEL values for lethality in animals in each duration category are recorded in Table 3-2 and 

plotted in Figure 3-2. 

Organotin Compounds. The oral administration of a proprietary drug, Stalinon, resulted in the deaths of 

about 100 people in France from an estimated 1,000 who had been treated for osteomyelitis, anthrax, and 

acne. Most of the 10 or more accounts of this 1954 tragedy are published in the French literature, but a 

summary can be found in WHO (1980). The primary ingredients in Stalinon were diethyltin diodide 

(15 mg/capsule) and linoleic acid (100 mg/capsule). It has been proposed that the deaths were caused by 

triethyltin iodide, which was present as an impurity from the manufacturing process. An estimate of 

70 mg of triethyltin has been calculated as the toxic dose for humans ingesting this compound over an 

8-day period (Barnes and Stoner 1959). A review by Boyer (1989) states that deaths occurred after 

exposure to an estimate dose of 3 g triethyltin iodide over a period of 6–8 weeks. However, many 

confounding variables in the reporting of this poisoning episode weaken the validity of these estimates. 

Kreyberg et al. (1992) described the case of a woman who ingested an unknown amount of trimethyltin 

and died 6 days after consuming the chemical; the main pathological findings were confined to the 

nervous system. 
TIN AND TIN COMPOUNDS 113 

3. HEALTH EFFECTS 

Lethal doses for monoorganotins ranging from 1,500 to more than 6,000 mg/kg have been reported for 

rodents suggesting that these compounds have relatively low toxicity (Pelikan and Cerny 1970). 

Acute-duration studies with dibutyltins have described lethal doses in rats between 20 and 50 mg/kg 

administered by gavage (Alam et al. 1993; Barnes and Magee 1958). In a 2-week dietary study, a dose of 

approximately 23 mg/kg/day was lethal to 6 out of 20 rats during the second week of the study (Seinen et 

al. 1977a). In a developmental study, daily gavage doses of 7.5 mg/kg/day administered on gestation 

days (Gds) 7–15 killed 5 out of 12 rats with a mean time of 8 days (Ema et al. 1991b). Long-term 

treatment (78-week study) with dibutyltin diacetate significantly decreased survival in rats and mice at the 

termination of the study (NCI 1978a). A dose of 7 mg dioctyltin dichloride/kg/day in the food was lethal 

to 10 out of 16 guinea pigs after 4–5 weeks of treatment (Seinen et al. 1977b). 

In male albino rats, the oral LD50 for tributyltin oxide was 148 mg/kg when the chemical was 

administered by gavage in corn oil and 194 mg/kg when administered as an aqueous suspension (Elsea 

and Paynter 1958). Three consecutive daily doses of 37.5 mg of tributyltin oxide/kg killed 6 out of 

50 rats (Elsabbagh et al. 2002). In pregnant mice, a dose of 27 mg/kg of tributyltin oxide administered 

during gestation was lethal to 3 out of 40 mice; no deaths occurred in controls (Faqi et al. 1997). Takagi 

et al. (1992) calculated a 2-week LD50 of approximately 150 mg/kg for tributyltin chloride in male 

hamsters and 172 mg/kg in females. 

Numerous studies provide information on the lethal effects of trimethyltins. In general, lethal doses, 

mostly in acute-duration studies, are below 10 mg/kg. For example, Brown et al. (1979) calculated an 

oral LD50 of 12.6 mg/kg in rats following a single gavage dose; most deaths occurred 2–5 days after 

dosing. Other studies have reported lethal single doses in rats of 5 mg/kg (Bouldin et al. 1981) and 

7 mg/kg (Alessandri et al. 1994). In a 2-week dietary study, doses of 2 mg/kg/day were lethal to 2 out of 

10 rats and doses of 6.7 mg/kg/day killed 10/10 rats in a few days (Snoeij et al. 1985). Three female 

hamsters that received a single dose of 4 or 5 mg/kg showed whole body tremors and were almost 

moribund when killed 4 days after dosing (Brown et al. 1984). In the same study, a single dose of 

3.75 mg/kg of trimethyltin chloride killed 4 out of 11 marmoset monkeys within 3 days of dosing (Brown 

et al. 1984). Single doses of 3–4 mg/kg were lethal to gerbils within a few days of treatment (Brown et al. 

1984; Nolan et al. 1990). 

Triethyltins are also highly toxic. In a 2-week study, doses of 6.7 mg/kg/day in the diet were lethal to 

3 out of 10 rats, but no lethality occurred with doses of 2 mg/kg/day (Snoeij et al. 1985). In an additional 
 

TIN AND TIN COMPOUNDS 114 

3. HEALTH EFFECTS 

2-week study, rats were gavaged with triethyltin bromide in water twice/week and a dose of 3 mg/kg 

killed 4 out of 10 rats after the third dose (Squibb et al. 1980). Four out of six rats died during the third 

week on a diet that provided 2 mg/kg/day of triethyltin hydroxide (Magee et al. 1957) and in an 11-week 

drinking water study with triethyltin sulfate in rats at dose levels of 1.4 mg/kg/day; deaths occurred after 

4 weeks (Smith 1973). 

An extensive listing of LD50 values for organotin compounds in several animal species can be found in 

Smith (1978) and WHO (1980). 

Reliable LOAEL values for lethality, and LD50 values in each species and duration category are recorded 

in Tables 3-3 through 3-8 and plotted in Figures 3-3 through 3-8. 

3.2.2.2 Systemic Effects 

No studies were located regarding musculoskeletal, or ocular effects in humans or animals after oral 

exposure to inorganic tin or organotin compounds. 

The highest NOAEL values and all reliable LOAEL values for systemic effects in each species and 

duration category are recorded in Table 3-2 and plotted in Figure 3-2 for inorganic tin compounds. 

Similar information is given in Tables 3-3 through 3-8 and Figures 3-3 through 3-8 for organotin 

compounds. 

Respiratory Effects. 

Inorganic Tin Compounds. No studies were located regarding respiratory effects in humans or in 

animals after oral exposure to inorganic tin compounds. 

Organotin Compounds. No histopathological alterations were observed in the lungs, bronchi, and 

trachea from rats and mice fed diets that provided up to 6.7 and 19.8 mg/kg/day of dibutyltin diacetate, 

respectively, for 78 weeks (NCI 1978a) or up to 3.8 and 9.8 mg/kg/day, respectively, of triphenyltin 

hydroxide for 78 weeks (NCI 1978b). Beagle dogs dosed with up to 0.62 mg triphenyltin 

hydroxide/kg/day for up to 52 weeks did not show any gross or microscopic alterations in the respiratory 

tract (Sachsse et al. 1987). Similar results were reported for rats dosed with up to 2.5 mg/kg/day of 

tributyltin oxide for 106 weeks (Wester et al. 1990). In a 6-week dietary study with dioctyltin dichloride 
 

TIN AND TIN COMPOUNDS 115 

3. HEALTH EFFECTS 

in rats, Seinen and Willems (1976) reported that rats dosed with approximately 16 mg/kg/day had grayish 

areas in the lungs at termination, suggesting chronic respiratory disease, and that three rats that died early 

in the study showed severe pneumonic alterations. No further relevant information was located. 

Cardiovascular Effects. 

Inorganic Tin Compounds. No studies were located regarding cardiovascular effects in humans after 

oral exposure to inorganic tin compounds. 

In a feeding study in rats, at dietary levels ranging from <10 to 315 mg/kg/day as stannous chloride for 

13 weeks, relative heart weights of males were higher than those of controls (De Groot et al. 1973). This 

effect was not dose-dependent and there were no associated histopathological findings. By itself, the 

significance of the observation is not clear. In a 4-week exposure to the same doses, there were no 

changes in heart weights (De Groot et al. 1973). 

Organotin Compounds. No studies were located regarding cardiovascular effects in humans after oral 

exposure to organotin compounds. 

No gross or microscopic alterations were observed in the heart of rats dosed with up to 5.7 mg dibutyltin 

dichloride/kg/day for 90 days (Gaunt et al. 1968). In a chronic-duration study, no histopathological 

alterations were observed in the hearts of rats and mice fed diets that provided up to 6.7 and 

19.8 mg/kg/day of dibutyltin diacetate, respectively, for 78 weeks (NCI 1978a). Similar findings 

regarding the heart were reported in chronic-duration studies with triphenyltin hydroxide in rats and mice 

dosed with up to 6.2 and 20 mg/kg/day, respectively, for 78–106 weeks (NCI 1978b; Tennekes et al. 

1989a, 1989b). Also, no cardiovascular effects were reported in dogs administered up to 0.62 mg 

triphenyltin hydroxide/kg/day for up to 52 weeks (Sachsse et al. 1987). 

Dietary treatment of rats with up to 16 mg dioctyltin dichloride/kg/day for 6 weeks (Seinen and Willems 

1976) or up to 2.5 mg tributyltin oxide/kg/day for 106 weeks (Wester et al. 1990) did not induce gross or 

microscopic alterations in the heart. 
TIN AND TIN COMPOUNDS 116 

3. HEALTH EFFECTS 

Gastrointestinal Effects. 

Inorganic Tin Compounds. There are several accounts of people who experienced gastrointestinal 

effects such as diarrhea, gastrointestinal pain, nausea, or gastroenteritis after ingestion of various foods 

stored in tin cans (WHO 1980, 2003). Doses ranged from 250 to 1,000 mg tin/kg body weight. Recent 

studies by Boogaard et al. (2003) showed that tin levels up to approximately 270 ppm in canned food 

caused no adverse effects in healthy humans. 

Data from studies in animals show that inorganic tin compounds can cause adverse gastrointestinal 

effects. Slightly distended small and large intestines were observed at necropsy of rats fed for 4 weeks 

diets containing 315–325 mg tin/kg/day as either stannous chloride or stannous orthophosphate. 

However, there were no histopathological changes (De Groot et al. 1973). In a 13-week study by the 

same investigators, doses of 95 mg Sn/kg/day as stannous chloride caused abdominal distension in rats 

during the first 2 weeks of the study, doses of 32 mg/kg/day caused no significant effects. Rats dosed 

with 315 mg/kg/day, which had to be terminated prematurely, showed distended intestines and slight 

ascites. 

In another study, effects on the morphology and on absolute and relative weights of the gastrointestinal 

tract were evaluated after feeding rats dietary levels of 7.9 and 15.9 mg tin/kg/day stannous chloride for 

4 weeks. Feed restriction was also studied in an attempt to distinguish between tin effects and the effects 

of decreased food intake and poor growth (Janssen et al. 1985). Increased relative weights of the 

stomach, cecum, and colon were observed at the lowest tin dose, but were apparently caused by 

diminished food intake since these changes were present in the pair fed controls as well as in the tin 

exposed animals. On the other hand, increases in the weight and length of the small intestines were 

observed to be independent of food consumption and thus a consequence of the exposure to stannous 

chloride. There was also an increase in the villus length, a decrease in the number of villi per unit 

surface, an increase in villus cell turnover, and changes in villi morphology in the intestines of the treated 

rats. Although similar changes of the intestinal villi were reported in another study (Dreef-van der 

Meulen et al. 1974), there are not enough data at this time to verify the intestinal changes as adverse. 

Mice fed 311–2,457 mg tin/kg/day as stannous chloride for 13 weeks showed gross distention of the 

cecum and reddened gastric mucosa at necropsy but no compound-related histopathological changes 

(NTP 1982). Similar findings were observed in rats fed 120–236 mg tin/kg/day (NTP 1982). However, 
 

TIN AND TIN COMPOUNDS 117 

3. HEALTH EFFECTS 

no such changes were observed in rats fed 32 or 63 mg tin/kg/day or mice fed 82 or 164 mg tin/kg/day as 

stannous chloride during a 105-week study (NTP 1982). 

Organotin Compounds. Limited information is available regarding gastrointestinal effects in humans 

after oral exposure to organotin compounds. Nausea and vomiting were reported in more than 70% of the 

individuals intoxicated presumably with triethyltin in a massive accidental poisoning episode in France in 

1954 (WHO 1980). Abdominal pain, diarrhea, nausea, and vomiting have been reported in cases of oral 

intoxication with triphenyltin (Lin and Hsueh 1993; Lin et al. 1998; Wu et al. 1990). 

Stomach distention was observed in rats 24 hours after a single dose of 50 mg dibutyltin dichloride/kg 

(Barnes and Magee 1958). The duodenum was also examined in many rats, but no changes were evident. 

Chronic studies with dibutyltin diacetate in rats and mice did not report any significant alterations in the 

gastrointestinal tract from rats or mice dosed with up to 6.7 and 19.8 mg/kg/day of the test material, 

respectively, for 78 weeks (NCI 1978a). 

Histopathological evaluation of the gastrointestinal tract (at six different levels) from rats dosed with up 

to approximately 16 mg dioctyltin dichloride/kg/day did not reveal any significant alterations (Seinen and 

Willems 1976). 

Single doses of 500 mg/kg of various tributyltin salts (chloride, acetate, benzoate, oleate) produced 

hemorrhages in the digestive tract of mice (Pelikan and Cerny 1968). Similar gross changes in the 

gastrointestinal tract were seen in another study in mice treated with much higher doses (4,000 mg/kg) of 

monobutyltin trichloride and other monobutyltin salts (Pelikan and Cerny 1970). No gastrointestinal 

alterations were observed in rats treated with up to 2.5 mg tributyltin oxide/kg/day for 106 weeks (Wester 

et al. 1990). 

No treatment-related alterations in the gastrointestinal tract were reported in rats, mice, and dogs in 

chronic-duration studies with triphenyltin hydroxide (NCI 1978b; Sachsse et al. 1987; Tennekes et al. 

1989a, 1989b). Rats were dosed with up to 6.2 mg/kg/day and mice were dosed with up to 20 mg/kg/day; 

the dogs were dosed with up to 0.62 mg/kg/day. 
 

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Hematological Effects. 

Inorganic Tin Compounds. No studies were located regarding hematological effects in humans after oral 

exposure to inorganic tin compounds. 

Data from 4-week feeding studies in rats showed some hematological changes (De Groot et al. 1973). A 

significant increase was observed in the hematocrit of male, but not in female, rats fed a dietary level of 

395 mg tin/kg/day as stannous sulfide. Both sexes of rats fed tin at dietary levels ranging from 68 to 

325 mg tin/kg/day as the chloride, orthophosphate, sulfate, oxalate, and tartrate showed anemia. The 

signs of anemia were decreased hematocrit, total erythrocytes, and hemoglobin levels. Lower mean 

corpuscular volume and hemoglobin concentrations were seen at the highest doses (225–325 mg 

tin/kg/day). In 13-week studies, stannic oxide produced no hematological changes in rats (De Groot et al. 

1973). However, dietary levels of 7.9 mg tin/kg/ as stannous chloride produced decreased 

hematological values in rats with 4-week exposures (Janssen et al. 1985). It is possible that the mineral 

content of the diet had an effect on the results of these studies since the no effect levels (22–440 mg 

Sn/kg/day) for hematological effects in studies with diets adequate in copper and iron (De Groot et al. 

1973; Dreef-van der Meulen et al. 1974) exceeded the LOAEL (7.9 mg/kg/day) from the work by Janssen 

et al. (1985) with diets that contained only one fifth as much iron and copper. Iron and copper are key 

nutrients in hematopoiesis; deficiencies in these elements are associated with microcytic anemias 

characterized by low hemoglobin and hematocrit values. It is suggested that the poor iron and copper 

nutrition in the Janssen et al. (1985) work was a predisposing factor, which amplified the adverse effects 

of tin on hematological parameters. This hypothesis is supported by studies in which the dietary 

concentrations of copper, tin, and iron were varied (De Groot 1973). High levels of copper and iron (well 

above dietary requirements) added to semipurified diets containing up to 75 mg/kg/day tin almost 

completely prevented hematological changes. Transient hemolytic anemia also was reported in rabbits 

treated daily by gavage with 10 mg tin/kg (as stannous chloride), the only dose tested, for 4 months 

(Chmielnicka et al. 1993). However, no information was provided in that study regarding the trace 

mineral composition of the diet. The NOAEL of 32 mg/kg/day for tin, as stannous chloride, in the 

13-week study by De Groot et al. (1973) was used to derive an intermediate-duration oral MRL for 

inorganic tin. 

Organotin Compounds. No studies were located regarding hematological effects in humans after oral 

exposure to organotin compounds. 
TIN AND TIN COMPOUNDS 119 

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Treatment of Fischer-344 rats with 5–6 mg dibutyltin dichloride/kg/day in the diet for up to 13 weeks 

produced a slight, but significant decrease in hemoglobin concentration in females after 6 weeks and in 

males after 13 weeks (Gaunt et al. 1968). This decrease was not associated with reductions of other 

erythrocyte parameters or with a reticulocytosis. Lower doses of approximately 3 mg/kg/day caused no 

significant effect. Differential leukocyte counts were not altered by treatment with dibutyltin dichloride. 

Decreased hemoglobin and hematocrit values, lowered mean corpuscular volume and hemoglobin mass, 

and decreased leucocytes were observed in rats fed a diet that provided approximately 4 and 

16 mg/kg/day tributyltin oxide for 4 weeks (Krajnc et al. 1984). Erythrocytes were reduced, and 

spherocytes and Howell-Jolly body-containing erythrocytes were increased in the 16 mg/kg/day group 

only. However, a study in Sprague-Dawley rats found no significant alterations in a complete set of 

hematological parameters following treatment with approximately 5 mg tributyltin oxide/kg/day for 

28 days (Verdier et al. 1991). The reason for the discrepancy between these two studies is unknown. In a 

2-year bioassay in Wistar rats, hematological determinations were made in weeks 13 and 53, and at 

termination (Wester et al. 1990). Significant hematological effects restricted to the high-dose males 

(dosed with approximately 2.1 mg/kg/day) were seen only at 12 months, and consisted of decreased 

hemoglobin, hematocrit, and mean corpuscular hemoglobin levels, and mean corpuscular volume (also at 

3 months. In females, there was an indication of increased young erythrocytes at 3 and 12 months, but the 

doses were not indicated. Leucocytes were decreased in high-dose males (24 months) and females 

(12 and 24 months). In a 22-week gavage study in Cynomolgus monkeys, treatment with doses of 

tributyltin oxide of 0.16 mg/kg/day (only dose level tested) decreased total leukocytes in weeks 8–10 at 

weeks 16–20 (Kerrer et al. 1992). The biological significance of this finding is unknown. 

In a 6-week dietary study with dioctyltin dichloride in male and female Wistar rats, hematological 

investigations conducted on blood collected at termination included hemoglobin concentration and total 

and differential leukocyte counts (Seinen and Willems 1976). Doses of approximately 16 mg/kg/day 

significantly decreased hemoglobin concentration in males, but there was no effect on total or differential 

leukocyte counts; the NOAEL for hemoglobin concentration was approximately 5.3 mg/kg/day. A study 

in female Balb/c mice treated by gavage with 500 mg dioctyltin dichloride/kg once per week for 8 weeks 

reported a 14% reduction in hemoglobin concentration at termination but no significant alterations in red 

or white blood cell counts (Miller et al. 1986). A dose of 100 mg/kg had no significant effect on 

hemoglobin concentration. 
 

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Triphenyltin hydroxide at a dose of 1.3 mg/kg/day caused a transient decrease in hemoglobin and 

hematocrit values at 26 and 52 weeks in female rats, but not in the males (Tennekes et al. 1989b). These 

changes were not apparent at 78 and 104 weeks (Tennekes et al. 1989b), nor were they seen in dogs given 

the same compound at doses of approximately 0.62 mg/kg/day for up to 42 weeks (Sachsse et al. 1987). 

Musculoskeletal Effects. 

Inorganic Tin Compounds. No studies were located regarding musculoskeletal effects in humans or 

animals following oral exposure to inorganic tin compounds. 

Organotin Compounds. No studies were located regarding musculoskeletal effects in humans following 

oral exposure to organotin compounds. Treatment of rats with up to 16 mg dioctyltin dichloride/kg/day 

for 6 weeks did not induce histopathological alterations in skeletal muscle (Seinen and Willems 1976). 

No treatment-related alterations in skeletal muscles were observed in a 104-week study in rats dosed with 

up to 6.2 mg triphenyltin hydroxide/kg/day or in mice dosed with up to 9.8 mg triphenyltin 

hydroxide/kg/day (Tennekes et al. 1989a, 1989b). Beagle dogs dosed with up to 0.62 mg triphenyltin 

hydroxide/kg/day for up to 52 weeks showed no gross or microscopic alterations in skeletal muscle or in 

the sternum bone (Sachsse et al. 1987). Similar findings were reported in a 106-week study with 

tributyltin oxide in rats dosed with to 2.5 mg/kg/day of the chemical (Wester et al. 1990). 

Hepatic Effects. 

Inorganic Tin Compounds. No studies were located regarding hepatic effects in humans after oral 

exposure to inorganic tin compounds. 

Hepatic effects have been observed following intermediate and chronic oral exposure of rats. Data from a 

4-week feeding study in Wistar rats showed some histopathological changes (De Groot et al. 1973). Both 

sexes fed tin as the chloride, orthophosphate, sulfate, oxalate, and tartrate had histopathological changes 

in the liver. The cytoplasm exhibited a clear homogeneous appearance, which suggested a disappearance 

of the cellular organelles and impaired cell function at the highest dietary level of 226–325 mg/kg/day and 

to a lesser extent at a level of 68–98 mg tin/kg/day (the doses varied with the tin compound used). A 

slight but definite oval cell type hyperplasia of the bile ducts was also apparent. Changes in organ 

weights were inconsistent. The authors suggested that the changes in liver cell morphology were due, in 
 

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part, to the reduced food intake and resultant impaired weight gain. These changes were apparent in the 

animals with the poorest weight gains. 

In a 13-week study in Wistar rats, histopathological changes were observed in the livers of both sexes at a 

dietary level of 315 mg tin/kg/day as stannous chloride, but in only a few rats at 95 mg tin/kg/day 

(De Groot et al. 1973). The changes were a homogeneous appearance of the cell cytoplasm and mild 

proliferation of the bile duct epithelium. Organ weights were not affected. In another 13-week study, 

similar changes were seen in the livers of rats fed a diet that was gradually increased to a final level of 

252 mg tin/kg/day as stannous chloride (Dreef-van der Meulen et al. 1974). 

No hepatic effects were reported in Fischer-344 rats and B6C3F1/N mice fed stannous chloride for either 

14 days or 13 weeks (NTP 1982). The highest dietary levels were 236 mg tin/kg/day as stannous chloride 

for rats and 2,457 mg tin/kg/day for mice. Considering the extremely high doses used, it is surprising that 

hepatic changes were not observed. 

Limited hepatic changes were seen following chronic oral exposure of rats and mice to stannous chloride. 

In a drinking water study at 0.7 mg tin/kg/day as stannous chloride for life, 80 rats were evaluated for 

hepatic and other health effects (Schroeder et al. 1968). There was a significant increase in fatty 

degeneration of the liver in the tin-exposed rats. Thirty-eight percent of the control rats had liver lesions, 

whereas 68% of the tin-exposed rats had liver lesions. Degeneration and necrosis, as well as fatty 

changes moderate to severe, were found in 55% of the control rats with lesions and in 65% of the tinexposed rats with lesions. Although similar hepatic effects were reported in the 105-week chronic 

bioassay of stannous chloride in rats and mice, the findings were not dose-related and comparable in 

treated and control animals (NTP 1982). 

Organotin Compounds. Liver impairment, as judged by increased serum levels of transaminases, was 

described in two cases of acute oral intoxication with triphenyltin (Lin et al. 1998; Wu et al. 1990). 

Hepatitis also was reported in three subjects who ingested between 20 and 50 grams of a preparation 

containing 45% triphenyltin acetate (Lin and Hsueh 1993). No further relevant information was located. 

Hepatic and bile duct effects were observed following acute and intermediate oral exposures of animals to 

organotin compounds. A single dose of dibutyltin dichloride of 50 mg/kg produced inflammation of the 

common bile duct of Wistar rats (Barnes and Magee 1958). Severe hepatic injury occurred in rats 

following three consecutive doses of 50 mg dibutyltin dichloride/kg/day; this treatment was lethal to 
TIN AND TIN COMPOUNDS 122 

3. HEALTH EFFECTS 

some rats in 6–10 days. The main features of the bile-duct injury included thickening, inflammation, and 

dilatation of the proximal duct. Histologically, the epithelium of the wall was replaced by granulomatous 

tissue. In cases in which the bile duct was perforated, severe peritonitis and fatty necrosis were seen. 

Multiple yellow infarcts developed in lobes of the liver, followed by inflammation of the portal blood 

vessels. In some cases, there was complete necrosis of the bile ducts. In rats examined 6–12 months after 

receiving the three doses of dibutyltin, the bile duct was shorter and thicker than normal and there was 

wall fibrosis in the adjacent pancreas, and in the portal tracts of the liver. Seinen et al. (1977a) noticed 

proliferation of the bile duct epithelium and periportal fibrosis in Wistar rats fed a diet that provided 

approximately 23 mg/kg/day of dibutyltin dichloride for 2 weeks; doses of 7.7 mg/kg/day caused no 

significant effect. Bile duct necrosis also was seen in Syrian hamsters treated with a single dose of 

30 mg/kg (Jang et al. 1986). Bile duct necrosis also occurred in mice, but not in rabbits or guinea pigs 

(20–50 mg/kg dose ranges) (Barnes and Magee 1958). No adverse hepatic effects (histopathology and 

serum transaminases) were reported in Fischer-344 rats dosed with up to 5.7 mg dibutyltin 

dichloride/kg/day for 90 days (Gaunt et al. 1968). In variance with the findings of bile duct necrosis in 

mice reported by Barnes and Magee (1958), Seinen et al. (1977a) did not observe histological changes in 

the liver from Swiss mice dosed with dibutyltin dichloride in doses of up to 30 mg/kg/day for 4 weeks; 

however, it is unclear whether the bile duct was examined. No microscopic alterations were reported in 

the liver from Fischer-344 rats or B6C3F1 mice treated with dibutyltin diacetate in doses of up to 6.7 and 

20 mg/kg/day, respectively, for 78 weeks (NCI 1978a). 

A significant increase in serum levels of ornithine carbamyl transferase (used as index of hepatotoxicity) 

was observed in albino mice gavaged once with 58 mg tributyltin chloride/kg (Ueno et al. 1994). The 

increase was first apparent 24 hours after dosing. Parallel experiments with dibutyltin dichloride and 

monobutyltin trichloride showed that the hepatotoxicity potency followed the order: dibutyltin !

tributyltin ! monobutyltin (Ueno et al. 1994). Monobutyltin was not hepatotoxic. Further studies by the 

same group of investigators showed that the liver toxicity of tributyltin chloride could be prevented by 

pretreatment of the mice with the cytochrome P-450 inhibitor SKF-525 (Ueno et al. 1995, 1997). 

Conversely, pretreatment with the P-450 inducer phenobarbital (PB) increased the toxicity of tributyltin 

chloride. These results suggest that the liver toxicity of tributyltin is due to a metabolite, most likely 

dibutyltin. Comparative studies with tributyltin and dibutyltin in mice and guinea pigs showed the mice 

to be much more sensitive to the hepatotoxicity of tri- and dibutyltin dichloride than guinea pigs (Ueno et 

al. 2003a), and this was correlated with differential inhibition of mitochondrial respiration in the two 

species. Additional experiments suggested that the difference in susceptibility between mice and guinea 

pigs might be due to the high affinity of butyltins, particularly dibutyltin, for hepatic mitochondria in 
TIN AND TIN COMPOUNDS 123 

3. HEALTH EFFECTS 

mice containing higher levels of sulfhydril groups relative to guinea pigs. In a three species comparison, 

the susceptibilities followed the order: mice ! rats ! guinea pigs (Ueno et al. 2003b). Kinetic studies 

showed that the differences in susceptibility appeared to be partly due to differences in metabolism of 

tributyltin and in the distribution of dibutyltin within cell organelles. In hepatocytes of mice treated with 

dibutyltin chloride, 41% of the dibutyltin was found in organelles compared to 27% in rats and 9% in 

guinea pigs (Ueno et al. 2003b). 

A single dose of 29.6 mg tributyltin chloride/kg (lowest dose tested) induced bile duct changes in Syrian 

hamsters consisting of adhesion in the liver, pancreas, and duodenum, and severe inflammation (Takagi et 

al. 1992). In a separate experiment, following a single dose of 44.4 mg/kg of tributyltin, the maximum 

concentrations of tributyltin and dibutyltin appeared in the liver 1 day after treatment and rapidly 

decreased thereafter. The concentration of dibutyltin was 10 times higher than that of tributyltin 1 day 

after dosing (Takagi et al. 1992). By day 14, neither compound could be detected in the liver, and 

aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-guanosine triphosphate 

(GTP), and alkaline phosphatase activities were not significantly different than control. These results 

suggest that dibutyltin has an important role in the hepatotoxicity of tributyltin. In a 4-week feeding 

study in Wistar rats, doses of approximately 16 mg tributyltin oxide/kg/day induced hepatic changes 

consisting of liver necrosis and bile duct hyperplasia (Krajnc et al. 1984). Slight atrophy of the 

hepatocytes was seen at 4 mg/kg/day and no significant alterations were seen at 1 mg/kg/day. Consistent 

with these observations, no microscopic changes were observed in the livers of Sprague-Dawley rats 

treated with 5 mg tributyltin oxide/kg/day for 28 days (Verdier et al. 1991). Cholangitis with biliary 

retention was reported in Fischer-344 rats dosed with tributyltin oxide at 16 mg/kg/day for 6 weeks 

(Carthew et al. 1992). In a 2-year bioassay with tributyltin oxide in Wistar rats, liver effects were 

restricted to high-dose rats (2.1 mg/kg/day) and consisted of slight bile duct changes (hyperplasia, cellular 

hypertrophy, minimal mononuclear cell infiltration) observed at 12 months, increased serum AST and 

ALT activities at 24 months, and an approximate 30% increase in absolute liver weight at termination; no 

histopathologic alterations were seen at 24 months (Wester et al. 1990). The NOAEL was 

0.25 mg/kg/day. 

No hepatotoxicity was seen in dogs exposed through the diet to up to 0.62 mg triphenyltin 

hydroxide/kg/day for up to 52 weeks (Sachsse et al. 1987). Hypertrophy of the smooth endoplasmic 

reticulum was reported in New Zealand rabbits exposed to approximately 17.4 mg triphenyltin 

acetate/kg/day via the diet for 70 days (Dacasto et al. 1994a). A dose-related trend towards portal 

sclerosis and bile duct proliferation was observed in Wistar rats given doses of 0.3–6.2 mg/kg/day 
TIN AND TIN COMPOUNDS 124 

3. HEALTH EFFECTS 

triphenyltin hydroxide for 52 and 104 weeks; there was no corresponding increase in liver weight 

(Tennekes et al. 1989b). The dose-related trend was stronger in females (p<0.0005) than in males 

(p<0.005). However, no liver pathology was reported in Fischer-344 rats dose with the same compound 

in doses of up to 3.8 mg/kg/day for 78 weeks (NCI 1978b). In NMRI mice, this same compound was 

associated with a 35–40% increase in relative liver weight and nodular hyperplasia at doses of 

15.2 mg/kg/day for males and 20.2 mg/kg/day for females but not at lower doses (Tennekes et al. 1989a). 

No significant liver alterations were reported in B6C3F1 mice in the 78-week bioassay with triphenyltin 

hydroxide (NCI 1978b). 

Studies with dioctyltin dichloride showed no significant histopathologic alterations in the livers from rats 

treated in the diet with doses of approximately 23 mg/kg/day for 2 weeks (Seinen et al. 1977a) or 

16 mg/kg/day for 6 weeks (Seinen and Willems 1976), or in guinea pigs treated with 8 mg/kg/day for 

4 weeks (Seinen et al. 1977a). No significant changes in liver weight were reported in mice gavaged with 

up to 500 mg/kg/day once per week for 8 weeks, but no other liver end points were evaluated (Miller et 

al. 1986). 

Renal Effects. 

Inorganic Tin Compounds. No studies were located regarding renal effects in humans after oral 

exposure to inorganic tin compounds. 

Histopathological changes in the kidneys were reported in Wistar rats that received dietary levels up to 

approximately 315 mg tin/kg/day as stannous chloride for 13 weeks (De Groot et al. 1973). The changes 

included large protein-like droplets in renal tubular epithelial cells. This appears to be a common finding 

in the strain of rats used in this study and did not appear to be related to tin exposure. The authors also 

mentioned the absence of calcareous deposits in the high-dose level female rats. This appears to be an 

unusual finding since these deposits are commonly seen with the species of rats used in the study. 

However, the toxicological significance of these kidney findings is not clear. 

In another 13-week study, Wistar rats that were fed the compound up to a maximum level of 252 mg 

tin/kg/day as stannous chloride showed increased relative kidney weights (Dreef-van der Meulen et al. 

1974). The protein-like droplets and calcareous deposits, which are common in the rat strains used, were 

present in the controls but were absent in the tin-fed animals. The absence of calcareous deposits in the 

females confirms the observations of De Groot et al. (1973), but the relevance of these finding to 
 

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3. HEALTH EFFECTS 

compound toxicity is unclear. The organ weight change itself, in the absence of histopathological or other 

effects, is usually not considered a toxic effect. 

Renal changes have been evaluated following chronic oral exposure of rats and mice to stannous chloride 

and the studies were described under Hepatic Effects. Vacuolar changes in the proximal convoluted 

tubules of the kidney were significantly increased in rats administered stannous chloride, compared with 

controls (Schroeder et al. 1968). However, in 14-day, 13-week, and 105-week studies of stannous 

chloride in rats and mice, no treatment-related nonneoplastic renal changes were reported (NTP 1982). 

Organotin Compounds. Acute nephropathy was reported in three subjects who ingested between 20 and 

50 grams of a preparation containing 45% triphenyltin acetate (Lin and Hsueh 1993). No further 

information was located regarding renal effects in humans after oral exposure to organotin compounds. 

Treatment of rats with up to 5.7 mg dibutyltin dichloride/kg/day for 90 days (Gaunt et al. 1968) or mice 

with up to 30 mg dibutyltin dichloride/kg/day (Seinen et al. 1977a) for 4 weeks did not induce any 

significant gross or microscopic alterations in the kidneys. Also, no significant renal effects were 

reported in rats or mice dosed with up to 6.7 or 19.8 mg dibutyltin diacetate/kg/day, respectively, for 

78 weeks (NCI 1978a). 

Rats dosed with up to approximately 23 mg dioctyltin dichloride/kg/day for 2 weeks showed no 

significant histopathological alterations in the kidneys at termination (Seinen et al. 1977a). However, 

treatment with approximately 16 mg/kg/day for 6 weeks produced signs of slight impairment of renal 

function (decreased specific gravity of the urine, increased BUN), but no histopathologic alterations were 

noticed (Seinen and Willems 1976). No significant alterations were observed in the kidneys from guinea 

pigs treated with up to 8 mg dioctyltin dichloride/kg/day for 4 weeks (Seinen et al. 1977a). 

Administration of a single dose of 4,000 mg/kg of tributyltin laureate to mice caused gross renal changes 

observed at necropsy 24 hours later (Pelikan and Cerny 1970). The kidneys were light red and slightly 

enlarged, and histopathological findings included steatosis of the renal cortical tubular epithelium and 

hyperemia of the renal medulla. In an intermediate-duration study, treatment of rats with doses of 

2.5 mg/kg/day of tributyltin chloride in the diet for 30 days did not cause any gross kidney alterations 

(Bressa et al. 1991). A significant increase (29–33%) in absolute kidney weight was observed in male 

and female rats dosed with approximately 2 mg tributyltin oxide/kg/day for 2 years (Wester et al. 1990). 

Increased urine production, seen after 3, 12, and 24 months of treatment, suggested a decreased renal 
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3. HEALTH EFFECTS 

concentration capacity, but microscopic examination of the kidneys did not reveal any significant 

treatment-related alterations. 

The renal effects of trimethyltin chloride were examined in male Wistar rats (Opacka and Sparrow 1985). 

Gavage administration of single doses (3, 6, or 10 mg/kg) of the tin compound significantly increased 

urine production over an observation period of 3 days; this effect was dose-related. Water consumption 

was significantly increased in the high-dose group beginning the first 24 hours after dosing. 

Histopathological examinations of the kidneys showed changes ranging from slight vacuolization of the 

proximal tubular cells with loss of brush borders at 3 mg/kg to extensive vacuolar degeneration with 

tubular dilation and evidence of regeneration in the 10 mg/kg dose-group. Severe nephrotoxicity was also 

reported in Long-Evans rats treated once with a dose of approximately 12 mg trimethyltin chloride/kg 

(Robertson et al. 1987). This dose was lethal to 16 out of 43 rats. Examination of the kidneys from 

surviving animals showed hyaline droplet inclusions, attenuated brush border, basolateral vacuolization, 

and eosinophilic granular casts in the proximal tubule cells. These lesions could be detected as early as 

2 days after dosing and were partially reversed during the 14-day observation period following treatment. 

Maximum severity was observed 7–11 days after treatment. 

Triphenyltin hydroxide did not induce morphological or functional alterations in the kidney from rats, 

mice, or dogs given doses of 0.6–20 mg/kg/day for up to 104 weeks (NCI 1978b; Sachsse et al. 1987; 

Tennekes et al. 1989a, 1989b). 

Endocrine Effects. 

Inorganic tin compounds. No studies were located regarding endocrine effects in humans following 

exposure to inorganic tin compounds. 

In a study in rats, there were no treatment-related alterations in the gross or microscopic appearance of the 

thyroid following dietary administration of up to 315 mg tin/kg/day as stannous chloride for 13 weeks 

(De Groot et al. 1973). No further relevant information was located. 

Organotin compounds. No information was located regarding endocrine effects in humans following 

oral exposure to organotin compounds. 
TIN AND TIN COMPOUNDS 127 

3. HEALTH EFFECTS 

Treatment of rats with up 5.7 mg dibutyltin dichloride/kg/day for 13 weeks did not induce any significant 

alterations in absolute or relative weight of the pituitary, thyroid, or adrenals or gross or microscopic 

appearance of these organs (Gaunt et al. 1968). Similar findings were reported for the adrenals of mice 

treated with up to 30 mg dibutyltin dichloride/kg/day for 4 weeks (Seinen et al. 1977a). Chronic-duration 

studies with dibutyltin diacetate also found no significant histopathological alterations in endocrine 

glands from rats and mice treated with doses of up to 6.7 and 19.8 mg/kg/day, respectively, for 78 weeks 

(NCI 1978a). 

Dietary exposure of rats to up to 23 mg dioctyltin dichloride/kg/day for 2 weeks had no significant effect 

on the weight or morphological appearance of the adrenals (Seinen et al. 1977a). Similar lack of effects 

was reported in the adrenals, thyroid, and pituitary glands from rats exposed to doses of up to 

16 mg/kg/day via the diet for 6 weeks (Seinen and Willems 1976). In contrast, guinea pigs exposed for 

4 weeks to 8 mg/kg/day showed a 50% increase in relative adrenal weight, suggesting that an increase of 

glucocorticoids may have been indirectly responsible for the thymus atrophy observed in this study 

(Seinen et al. 1977a). No significant effects were seen at 4 mg/kg/day. 

Administration of a single gavage dose of 60 mg tributyltin oxide/kg to Wistar rats had no significant 

effect on the weight of the adrenals (Raffray and Cohen 1993). Treatment of male Fischer-344 rats with a 

single dose of 100 mg/kg of tributyltin oxide increased serum cortisol levels and induced adrenal 

hypertrophy (Funahashi et al. 1980). It also caused changes consistent with activation of both secretion 

and synthesis of ACTH, and to subsequent adrenal hypertrophy. Serum levels of thyroxine (T4) and 

thyrotrophin (TSH) were markedly reduced, but the intensity of TSH cells staining was increased, 

suggesting that tributyltin oxide inhibited TSH release, which caused thyroid hypofunction. Since the 

decrease in circulating T4 was much more pronounced than that of TSH, Funahashi et al. (1980) 

suggested that tributyltin oxide has a direct effect on the thyroid. Most acute effects appeared to be 

reversible within 14 days. Treatment of rats with 6 mg/kg/day for 26 weeks increased adrenals and 

hypophysis weight and caused signs of thyroid hypofunction (Funahashi et al. 1980). In a study by 

Krajnc et al. (1984), Wistar rats were fed diets that provided approximately 0, 1, or 4 mg tributyltin 

oxide/kg/day for 6 weeks. Treatment with 4 mg/kg/day significantly decreased serum levels of T4 and 

TSH, whereas luteinizing hormone (LH) was significantly increased. Both exposure levels decreased 

insulin levels in serum; however, the results of a glucose tolerance test were unremarkable, suggesting 

that the decrease in serum insulin may have been due to a marked decrease in feed intake. No significant 

changes were measured in concentrations of follicle-stimulating hormone (FSH) and corticosterone. 

Release of TSH after administration of thyrotropin-releasing hormone (TRH) was slightly reduced at 
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3. HEALTH EFFECTS 

4 mg/kg/day, but release of both LH and FSH were enhanced. Light microscopy revealed flattening of 

the epithelial lining of the thyroid follicles at 4 mg/kg/day, but not at lower doses. In the pituitary, 

treatment with 4 mg/kg/day tributyltin oxide reduced the number of TSH-immunoreactive cells and the 

staining intensity, increased the number of cells staining for LH, and had no significant effect in the 

staining for GH-, FSH-, or ACTH-producing cells. Krajnc et al. (1984) concluded that their results 

suggested that treatment with tributyltin oxide for 6 weeks did not stimulate the pituitary-adrenal axis. In 

a 2-year dietary study with tributyltin oxide in Wistar rats, no significant alterations were observed at 

12 and 24 months in serum levels of TSH, LH, FSH, insulin, T4, or free thyroxine (FT4) with a dose level 

of up to 2.1 mg/kg/day (Wester et al. 1990). However, decreased thyroid follicular epithelial cell height 

was observed at 12 and 24 months. Treatment of pregnant rats with t10 mg tributyltin chloride/kg/day on 

Gds 0–19 significantly reduced serum T4 and T3, and treatment with t2.5 mg/kg/day on Gds 8–19 

significantly reduced only T4 (measurements were conducted on Gd 20) (Adeeko et al. 2003). 

No significant gross or microscopic alterations were seen in the adrenal, thyroid, and parathyroid glands 

of dogs dosed with up to 0.62 mg triphenyltin hydroxide/kg/day in the diet for up to 52 weeks (Sachsse et 

al. 1987). Triphenyltin hydroxide caused dose-related cystoid changes in the pars intermedia of the 

pituitary gland from male and female Wistar rats administered this compound for 52 or 104 weeks at 

doses of 0.3–6.2 mg/kg/day (Tennekes et al. 1989b). At the highest dose, up to 40% of the males and 

80% of the females were affected at 52 weeks. At the end of 104 weeks, 72.3% of the high dose males 

and 55.6% of the females exhibited the cystoid changes. The lower incidence in females at 104 weeks 

was related to a high early mortality from fatal pituitary adenomas (see Section 3.2.2.7). However, no 

significant histopathological alterations were observed in endocrine organs from male or female 

Fischer-344 rats treated with up to 3.8 mg/kg/day of the test material in the diet for 78 weeks (NCI 

1978b). Also, chronic treatment of mice with up to 20 mg triphenyltin oxide/kg/day did not result in 

histopathological alterations in endocrine glands (NCI 1978b; Tennekes et al. 1989a). 

Studies conducted by Ohhira and coworkers showed that administration of a single dose of 50 mg of 

triphenyltin chloride/kg produced transient hyperglycemia and hypertriglyceridemia in hamsters but not 

in rats (Ohhira and Matsui 1996). Kinetic studies showed that hamsters accumulated significantly more 

triphenyltin in the pancreas than did rats, and peak levels of triphenyltin in the pancreas correlated well 

with peak levels of glucose in plasma. Additional studies by these investigators showed that pretreatment 

of hamsters with the cytochrome P-450 inducer phenobarbital (PB) suppressed the diabetogenic effects of 

triphenyltin compared to PB-untreated hamsters (Ohhira et al. 1999). Pretreatment with the CYP1A and 

2A inducers E-naphthoflavone and 3-methylcholanthrene, respectively, was not as effective as 
 

 

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pretreatment with PB in preventing the organotin-induced hyperglycemia and hypertriglyceridemia. On 

the other hand, pretreatment with the P-450 inhibitor, SKF-525A, increased the diabetogenic effects of 

triphenyltin (Ohhira et al. 2000). Overall, these findings suggested that the hyperglycemic toxicity of 

triphenyltin is due primarily to accumulation of the parent compound, triphenyltin, in the pancreas. 

Dermal Effects. 

Inorganic Tin Compounds. No studies were located regarding dermal effects in humans or animals after 

oral exposure to inorganic tin compounds. 

Organotin Compounds. No studies were located regarding dermal effects in humans after oral exposure 

to organic tin compounds. 

Administration of dibutyltin diacetate to rats (6.7 mg/kg/day) and mice (19.8 mg/kg/day) for 78 weeks did 

not cause any significant alteration in the skin (NCI 1978a). Similar findings were reported in rats dosed 

with up to 16 mg dioctyltin dichloride/kg/day for 6 weeks (Seinen and Willems 1976). 

No skin alterations were observed in rats dosed with up to 3.8 mg dibutyltin diacetate/kg/day for 

78 weeks or in mice dosed with up to 9.8 mg/kg/day for the same duration (NCI 1978b). In female mice, 

a dose of 20.2 mg/kg/day triphenyltin hydroxide administered for 80 weeks was associated with dermal 

sores and burn-like lesions, and was sometimes accompanied by hair loss (Tennekes et al. 1989a). These 

lesions were present primarily in the cervical area of the back, but were also identified on the head, ears, 

forelimb, and abdomen. Males were affected to a much lesser extent than the females. No skin lesions 

were associated with the chronic administration of triphenyltin hydroxide to rats or dogs (Sachsse et al. 

1987; Tennekes et al. 1989b). 

Ocular Effects. 

Inorganic Tin Compounds. No studies were located regarding ocular effects in humans or animals after 

oral exposure to inorganic tin compounds. 

Organotin Compounds. No studies were located regarding ocular effects in humans after oral exposure 

to organic tin compounds. The only information available in animals is that no ophthalmologic 

alterations were observed in rats treated with up to 6.2 mg triphenyltin hydroxide/kg/day or in mice dosed 
 

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with up to 20.2 mg/kg/day of the same compound for 80–104 weeks and examined at 6, 12, and 

18 months (Tennekes et al. 1989a, 1989b). Dogs dosed with up to 0.62 mg triphenyltin hydroxide/kg/day 

for up to 2 weeks also exhibited no gross or histologic alterations in the eyes (Sachsse et al. 1987). 

Body Weight Effects. 

Inorganic Tin Compounds. Reductions in body weight, food intake, and water consumption were 

observed in oral studies of inorganic tin compounds. Decreases in body weights and reduced food intake 

were recorded in studies in which stannous chloride and other inorganic tin (7.9 mg tin/kg/day) 

compounds were administered to rats for acute and intermediate durations (De Groot et al. 1973; Janssen 

et al. 1985). This was usually accompanied by reduced food consumption. However, these parameters 

were comparable between control and treated rats fed stannous chloride during chronic studies (NTP 

1982; Schroeder et al. 1968). The findings appear to suggest direct action of some inorganic tin 

compounds on growth and food intake after acute- and intermediate-duration dosing but not during 

chronic dosing. When assessing effects of inorganic tin on growth, it is important to monitor the status of 

some essential minerals such as zinc, since reduced growth is a common symptom of zinc deficiency and 

excess dietary tin reduces zinc absorption (Greger and Johnson 1981; Johnson and Greger 1982). 

Organotin Compounds. Reduced body weight gain and even body weight loss have been reported in 

numerous studies with organotins following various exposure durations. In some cases, but not all, 

information on food and water consumption was also provided. Rats treated once daily for 3 days with 

40 mg dibutyltin laureate/kg/day lost weight, and a dose level of 20 mg/kg/day significantly reduced body 

weight gain (Khaliq et al. 1991). In a 2-week dietary study in rats, a dose level of 23 mg/kg/day of 

dibutyltin dichloride reduced final body weight by 20%, a lower dose of 7.7 mg/kg/day was without 

significant effect (Seinen et al. 1977a). No significant effect on body weight was reported in a 90-day 

dietary study in rats dosed with up to 57 mg/kg/day of dibutyltin dichloride (Gaunt et al. 1968). Mice 

treated for 4 weeks with up to 30 mg/kg/day of dibutyltin dichloride also showed no treatment-related 

effects on body weight (Seinen et al. 1977a). Chronic-duration studies with dibutyltin diacetate did not 

report significant differences in body weight between treated and control groups of rats and mice treated 

with up to 6.7 and 19.8 mg/kg/day, respectively, for 78 weeks (NCI 1978a). 

Doses of 23 mg/kg/day of dioctyltin dichloride for 2 weeks reduced final body weight in rats by 

approximately 12% relative to controls; the NOAEL was 7.7 mg/kg/day (Seinen et al. 1977a). A 7–9% 

reduction in final weight was seen in a 6-week dietary study in rats that received doses of up to 
TIN AND TIN COMPOUNDS 131 

3. HEALTH EFFECTS 

16 mg/kg/day of dioctyltin dichloride (Seinen and Willems 1976). Since food consumption was 

practically unaffected, the authors suggested that the treatment slightly lowered food efficiency. Guinea 

pigs seemed more susceptible to treatment with dioctyltin dichloride since a 4-week treatment with 

8 mg/kg/day caused a 43% reduction in final body weight and half that dose reduced it by 13% (Seinen et 

al. 1977a). 

Single-dose studies with tributyltin oxide and chloride reported reduced weight gain and weight loss that 

became noticeable 48 hours following doses of 30–50 mg/kg (Ema et al. 1991a; Raffray and Cohen 

1993). Significant weight loss was also reported in rats following 6 days of treatment with 2.5 mg/kg/day 

of tributyltin bromide (Yallapragada et al. 1991). A single dose of 100 mg/kg of tributyltin chloride 

produced a 13% reduction in body weight in hamsters 2 weeks after dosing (Takagi et al. 1992). 

Intermediate-duration studies with tributyltins have reported alterations in body weight in the range of 

2.5–16 mg/kg/day (Bressa et al. 1991; Funahashi et al. 1980; Krajnc et al. 1984). In a 106-week study, 

body weights of rats were unaffected up to week 67, at which time, body weights of high-dose males 

(2.1 mg/kg/day) began to decrease (Wester et al. 1990); no quantitative data were provided. 

Acute studies with triethyltin reported weight loss with doses 0.5 mg/kg/day (Yallapragada et al. 1991), 

and significant weight loss was reported in an intermediate-duration study with doses of 0.8 mg/kg/day in 

drinking water (Reiter et al. 1980). The lowest dose of trimethyltin that caused weight loss in rats in an 

acute study was 2.5 mg/kg/day (Yallapragada et al. 1991). 

Intermediate-duration studies with triphenyltins reported a 25% reduction in body weight gain in rats 

following 7 weeks on a diet that provided 5 mg/kg/day of triphenyltin hydroxide (NCI 1978b). Rabbits 

also experienced a significant reduction in final weight gain following 70 days of treatment with 

approximately 17 mg triphenyltin acetate/kg (Dacasto et al. 1994a). Triphenyltin hydroxide was also 

associated with reduced body weight in male NMRI mice following 80 weeks on a diet that provided 

15.2 mg/kg/day of the chemical (Tennekes et al. 1989a). No significant alterations in body weight gain 

were reported in dogs dosed with up to 0.62 mg triphenyltin hydroxide/kg/day for up to 52 weeks 

(Sachsse et al. 1987). 

3.2.2.3 Immunological and Lymphoreticular Effects 

Inorganic Tin Compounds. No studies were located regarding immunological effects in humans after 

oral exposure to inorganic tin compounds. 
 

 

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The only information available regarding effects in animals is that from a study by De Groot et al. (1973), 

which observed no significant histological alterations in the thymus and spleen from rats fed a diet that 

provided up to 440 mg Sn/kg/day as stannous oxide or up to 315 mg Sn/kg/day as stannous chloride for 

13 weeks. 

Organotin Compounds. No studies were located regarding immunological effects in humans after oral 

exposure to organotin compounds. 

Numerous studies have shown that the lymphoreticular system, specifically the thymus, is the main target 

for some organotin compounds. For example, in Wistar rats fed diets that provided approximately 7.7 mg 

of dibutyltin dichloride/kg/day (the lowest dose tested) for 2 weeks, there was approximately a 50% 

reduction in relative thymus weight accompanied by lesser reductions in the relative weight of the spleen 

and popliteal lymph nodes (Seinen et al. 1977a). All treated rats showed marked lymphocyte depletion in 

the thymus, particularly the thymic cortex, but no signs of cell destruction could be seen. Rats dosed with 

23 mg/kg/day showed almost complete depletion of lymphocytes. In addition to the thymus, lymphocyte 

depletion was evident in thymus-dependent areas of the spleen and popliteal nodes. Similar results were 

obtained with dioctyltin dichloride (Seinen and Williams 1977a). A 4-week dosing with dioctyltin 

dichloride followed by an 8-week period on a control diet showed that the effects on the thymus were 

completely reversed within 2 weeks after treatment ceased. Similar experiments conducted with 

diethyltin dichloride and dipropyltin dichloride showed similar but less pronounced effects. In contrast, 

dimethyltin dichloride, didodecyltin dibromide, dioctadecyltin dibromide, monooctyltin trichloride, 

trioctyltin chloride, and tetraoctyltin did not induce atrophy of the lymphoid organs (Seinen et al. 1977a). 

Functional changes occurring in conjunction with the loss thymus weight and cellularity included a 

depression in the humoral response to immunization with sheep red blood cells (SRBC) in rats dosed with 

approximately 5 mg of dibutyltin dichloride/kg/day for 4–6 weeks and a significant delay in an allograft 

response at 15 mg/kg/day (Seinen et al. 1977b). Rats treated similarly with a 5 mg/kg/day dioctyltin 

dichloride exhibited a depressed delayed-type hypersensitivity (DTH) to tuberculin, a cell-mediated 

immunity parameter. Seinen et al. (1977b) also showed that the immune effects were more pronounced in 

rats exposed in the developmental phase of the lymphoid system. The immune effects of these organotin 

compounds were not induced by stress-related release of glucocorticoids, since adrenalectomy did not 

prevent the reduction in thymus weight (Seinen and Willems 1976). In addition, relative adrenal weight 

was unaffected in these studies and there were no histological signs of hyperactivity in the adrenal cortex 
TIN AND TIN COMPOUNDS 133 

3. HEALTH EFFECTS 

(Seinen and Willems 1976). The findings of Seinen et al. (1977b) with dibutyltin dichloride in rats were 

used as basis for derivation of an intermediate-duration oral MRL for dibutyltin dichloride. 

In contrast to rats, the immune functions of Swiss mice were unaffected by exposure to up to 

approximately 30 mg dibutyltin dichloride/kg/day for 4 weeks (Seinen et al. 1977a), and neither were the 

immune functions of guinea pigs treated with approximately 7 mg dioctyltin dichloride/kg/day for 5– 

7 weeks (Seinen et al. 1977b). However, exposure of Hartley guinea pigs to higher doses of dioctyltin 

dichloride for 4 weeks caused a reduction of the size of the thymus and its relative weight by about 37% 

compared with controls, and a marked depletion of lymphocytes in the thymic cortex (Seinen et al. 

1977a). Treatment of Balb/c mice with a much higher dose of 500 mg dioctyltin dichloride/kg by gavage 

once per week for 8 weeks caused a reduction in relative thymus weight of approximately 67% relative to 

controls, and no significant changes occurred at 100 mg/kg (Miller et al. 1986). 

Snoeij et al. (1985) studied the effects of a series of triorganotins in Wistar rats fed the compounds in the 

diet for 2 weeks. At doses of approximately 20 mg/kg/day, tripropyltin chloride, tributyltin chloride, and 

triphenyltin chloride induced a reduction in relative thymus weight of 47, 61, and 19%, respectively, 

relative to controls, and caused reduction of cellularity in the thymus. These effects were completely 

reversed within 2 weeks. Trihexyltin chloride was less effective, whereas trioctyltin chloride was 

ineffective. Trimethyltin chloride and triethyltin chloride were primarily neurotoxic (see Section 3.2.2.4). 

In a 70-day dietary study in New Zealand rabbits, a dose of approximately 17.4 mg triphenyltin 

acetate/kg/day caused blurring of the demarcation between cortex and medulla of the thymus and 

depletion of lymphocytes in the cortex (Dacasto et al. 1994a). Also, lymph nodes showed decreased 

cellularity in the thymic-dependent areas. 

A chronic-duration dietary study with dibutyltin dichloride did not report histopathological alterations in 

lymphoid tissues of Fischer-344 rats and B6C3F1 mice following treatment with doses of up to 6.7 and 

19.8 mg/kg/day, respectively, for 78 weeks (NCI 1978a, 1978b). Long-term studies with triphenyltin 

hydroxide reported a reduction in serum immunoglobulins in Wistar rats following treatment with a dose 

of 0.3 mg/kg/day and higher for 52 weeks (Tennekes et al. 1989b), and in NMRI mice following 

administration of 15.2 mg/kg/day for 80 weeks (Tennekes et al. 1989a). No histopathological effects 

were observed in lymphoid tissues from Fischer-344 rats or B6C3F1 mice administered up to 3.8 and 

9.8 mg of triphenyltin hydroxide/kg/day, respectively, for 78 weeks (NCI 1978a, 1978b), or in dogs dosed 

with up to 0.62 mg/kg/day for 52 weeks (Sachsse et al. 1987). No tests of immunocompetence were 

conducted in any of these long-term studies. 
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3. HEALTH EFFECTS 

Several additional acute- and intermediate-duration studies with tributyltin hydroxide (and also oxide) 

have reported decreased weight in lymphoid organs (Bressa et al. 1991; Carthew et al. 1992; Funahashi et 

al. 1980; Krajnc et al. 1984; Raffray and Cohen 1993; Smialowicz et al. 1989, 1990; Vandebriel et al. 

1998; Vos et al. 1990). Other immune parameters such as the primary immune response to SRBC and 

lymphoproliferative responses to stimulation with mitogens were affected by exposure to tributyltin oxide 

(Smialowicz et al. 1989, 1990). Furthermore, comparative 3-week studies in adult and preweanling 

Fischer-344 rats showed that younger animals were more sensitive to the immunosuppressive effects of 

tributyltin oxide than mature rats (Smialowicz et al. 1989). A 4.5–6-month dietary study in male Wistar 

rats showed that doses of 0.25 mg tributyltin oxide/kg/day, or higher, altered both parameters of specific 

resistance and nonspecific resistance (Vos et al. 1990). Neither the IgM nor the IgG response to 

ovalbumin and T. spiralis were altered after 5.5 months, but the IgE responses to T. spiralis was 

suppressed in a dose-related manner (significant at 0.25 mg/kg/day). The DTH reactions to ovalbumin 

and tuberculin were not significantly altered after 6 months of dosing. There also was an increased 

number of larvae of T. spiralis in muscle after infection at 0.25 mg/kg/day after 5.5 months of exposure 

to the test compound. There was no significant effect on the response of spleen cells to T- and 

B-mitogens after 4.5 months of treatment. The cell surface marker analysis of mesenteric lymph node 

cells showed a reduction in the relative count of T-lymphocytes and an increase in the percentage of 

B-lymphocytes at 0.25 mg/kg/day after 6 months. The in vivo clearance of L. monocytogenes was 

impaired at 2.5 mg/kg/day after 5 months of treatment. Treatment with tributyltin oxide for 4.5 months 

had no significant effect on natural killer cell activity of spleen and peritoneal cells. No significant effects 

were seen at 0.025 mg/kg/day and this dose, the study NOAEL, was used to derive an intermediateduration oral MRL for tributyltin oxide. The same tests conducted after groups of rats had been on the 

experimental diets for 15–16.5 months yielded similar results and a LOAEL was defined at 

0.25 mg/kg/day for depression of IgE titers and increased T. spiralis larvae in muscle after 16.5 of dosing; 

the NOAEL was 0.025 mg/kg/day and was used to derive a chronic-duration oral MRL for tributyltin 

oxide. 

In another 2-year study of tributyltin oxide in Wistar rats, doses of 2.1–2.5 mg/kg/day significantly 

increased serum immunoglobin A (IgA) after 12 and 24 months in males and females, decreased IgG in 

females after 3 and 13 months, and increased IgM after 3, 12, and 24 months (Wester et al. 1990). There 

were no histopathological changes in the thymus or lymph nodes, but the spleen showed decreased 

hemosiderin content after 12 months of exposure in males and females. No significant effects were seen 

with doses of approximately 0.2 mg/kg/day. 
 

 

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The highest NOAEL values and all reliable LOAEL values for immunological effects in each species and 

duration category are recorded in Tables 3-3 through 3-8 and plotted in Figures 3-3 through 3-8 for 

organotin compounds. 

3.2.2.4 Neurological Effects 

Inorganic Tin Compounds. No studies were located regarding neurological effects in humans after oral 

exposure to inorganic tin compounds. 

In the studies of systemic and other effects of inorganic tin compounds in animals (Sections 3.2.2.1 and 

3.2.2.2), clinical signs of neurotoxicity or behavioral changes were not noted. However, central nervous 

system effects in animals consisting of ataxia, muscular weakness, and depression have apparently been 

associated with oral exposure to the inorganic compounds (WHO 1980). Histopathological examinations 

of rats fed levels of 315 mg tin/kg/day as stannous chloride for 8–9 weeks revealed a spongy state of the 

white matter of the brain (De Groot et al. 1973). However, the treatment of these animals was terminated 

at 9 weeks because of the number of rats that were dead or moribund. It is, accordingly, difficult to 

determine if the tissue changes observed were due to a direct effect of tin on the brain or were secondary 

to the poor health of the animals. There were no other neurological changes reported and the meaning of 

the finding is not clear. 

Organotin Compounds. Death and intoxication resulting from the Stalinon incidents are described in 

Section 3.2.2.1. Stalinon contained diethyltin diodide and an undetermined amount of triethyltin iodide. 

It has been proposed that the effects were caused by triethyltin iodide, which was present as an impurity 

from the manufacturing process (WHO 1980). Symptoms in the affected persons appeared suddenly, 

about 4 days following ingestion of the drug, and included vertigo, intense headache, photophobia, altered 

consciousness, visual impairment, and convulsions. Sensory disturbances, hypoflexia, and loss of 

sphincter control were common observations. Deaths occurred after 4–10 days as the result of deep 

coma, or more frequently, acute intracranial hypertension. Autopsies revealed diffuse edema in central 

nervous system white matter (Foncin and Gruner 1979). Kreyberg et al. (1992) described the 

neuropathological effects associated with a fatal case of trimethyltin intoxication. A few hours after the 

intoxication, the patient experienced tinnitus, lightheadedness, aggression, and episodes of 

unresponsiveness. The patient died of multiorgan failure six days after consumption of the chemical. 

Postmortem examination revealed generalized chromatolysis of the neurons in the brain, spinal cord, and 
TIN AND TIN COMPOUNDS 136 

3. HEALTH EFFECTS 

spinal ganglia. There was recent neuronal necrosis in the fascia dentata of the hippocampus and spinal 

ganglia, and also in the pyramidal cell layer of the hippocampus, cerebral cortex, basal ganglia, and 

Purkinje cell layer of the cerebellum. Kreyberg et al. (1992) noted that some of these changes could have 

been caused by an anoxic episode shortly before death. Ultrastructurally, there was marked accumulation 

of lysosomal dense bodies and disorganization of the granular endoplasmic reticulum in the neurons. 

Acute intoxication with an unknown amount of triphenyltin produced severe ataxia, dysmetria, 

nystagmus, and blurring of vision in a 23-year-old male (Wu et al. 1990). Twelve days later, the patient 

developed disturbance of consciousness and confusion that lasted for 2 months. Electrophysiological 

tests revealed a delayed sensorimotor polyneuropathy due to axonal degeneration and demyelination. Lin 

et al. (1998) described an additional case of triphenyltin intoxication in a 19-year-old female who 

presented with spontaneous involuntary movement of the hands, facial twitching, diplopia, drowsiness, 

giddiness, vertigo, bidirectional nystagmus, impairment of calculations ability, and disorientation to 

people, time, and places. No seizures occurred, but 12 days after the poisoning episode the 

electroencephalogram (EEG) showed mild cortical dysfunction. Follow-up of the patient showed 

complete recovery within a year. 

The effects associated with oral exposure of animals to triorganotins, particularly trimethyltin and 

triethyltin, have been described in a number of studies conducted mostly in rats. End points that have 

been monitored include neurochemistry, neurophysiology, and behavior. While the main target of both 

trimethyltins and triethyltin is the nervous system, exposure to trimethyltin is characterized by neuronal 

necrosis, particularly in the hippocampus, whereas triethyltin treatment causes primarily intramyelinic 

edema. Rats dosed in the food with approximately 2 mg triethyltin oxide/kg/day (only dose level tested) 

for 2 weeks had ataxia and paralysis of the hind limbs (Magee et al. 1957). Necropsy revealed swelling in 

the brain and spinal cord with compression of structures. Microscopic examination revealed interstitial 

edema of the white matter in all sections of the central nervous system; neurons of the brain and spinal 

cord seemed not to be affected. Rats that survived the treatment for 2 weeks followed by doses of 

1 mg/kg/day for 6 weeks and then 4 months on a normal diet did not show evidence of the characteristic 

edema or obvious loss of myelinated fibers. Similar results were reported by in Osborne-Mendel rats 

dosed with approximately 2.8 mg triethyltin sulfate/kg/day in the drinking water for 22 days (Graham and 

Gonatas 1973). Signs of motor dysfunction were evident between the 10th and 17th day of intoxication. 

There was also greater involvement of the anterior than the posterior nerve roots, both of which showed 

more intramyelinic vacuole formation and splitting than did the sciatic nerve. Older rats appeared more 

susceptible than younger rats. Exposure of Sprague-Dawley rats to approximately 0.7–1.4 mg triethyltin 
TIN AND TIN COMPOUNDS 137 

3. HEALTH EFFECTS 

sulfate/kg/day in the water for 3 months caused mild brain edema as early as day 10 (Eto et al. 1971). 

After 30 days, there was a noticeable decrease in the amount of stainable myelin. In the treated rats, the 

yield of myelin per brain was reduced by half, but the isolated myelin appeared morphologically normal. 

Analysis of whole brains showed decreased proteolipid protein and total lipid, particularly galactolipids. 

Eto et al. (1971) hypothesized that treatment with triethyltin causes nonspecific chemical abnormalities in 

the myelin sheath undergoing secondary degeneration. Some Wistar rats treated with approximately 

1.4 mg triethyltin sulfate/kg/day in the water developed weakness and paralysis after 4 weeks of treatment 

and some died (Smith 1973). Necropsy showed edema of the brain and spinal cord. 

In a 2-week dietary study with several trialkyltin compounds in male Wistar rats, Snoeij et al. (1985) 

observed that triethyltin chloride and trimethyltin chloride were neurotoxic (cerebral edema and neuronal 

necrosis, respectively), whereas tripropyltin chloride, tributyltin chloride, and triphenyltin were mainly 

immunotoxic (see Section 3.2.2.4), trihexyltin chloride was slightly immunotoxic, and trioctyltin chloride 

was not toxic at the doses tested. 

In addition to examination of the morphological effects of triethyltin, behavioral testing has also been 

conducted. In male CD rats, no toxic signs were seen during treatment with 1 mg triethyltin 

bromide/kg/day twice per week (1, 2, or 3 mg/kg/day) for 2 weeks (Squibb et al. 1980). However, grip 

strength (hindlimb and forelimb) was significantly reduced during the second week of treatment at 

2 mg/kg even during a week free of treatment. Four weeks after treatment ceased, limb strength had 

returned to normal (1 and 2 mg/kg). Startle responsiveness was significantly reduced at 1 and 2 mg/kg, 

beginning the first week of treatment, but recovered in the posttreatment period. Two weeks after start of 

treatment, all treated groups showed edema of the white matter in the central nervous system but none 

was seen in the sciatic nerve. There appeared to be no neuronal damage. Partial recovery of the lesions 

was seen 4 weeks after treatment ceased. In another drinking water study, repeated doses of triethyltin 

bromide (0.4–0.8 mg/kg/day) produced performance decrements in a series of behavioral toxicity tests in 

rats (Reiter et al. 1980). The effects were rapid in onset, but were reversible 1 month after exposure was 

discontinued. Such findings correlate well with effects on the myelin sheath (i.e., demyelination). 

The neurotoxicity of trimethyltin has been examined in numerous acute-duration studies and in a smaller 

number of intermediate-duration studies. Bouldin et al. (1981) conducted a detailed analysis of the 

morphological effects of trimethyltin hydroxide in adult and neonatal Long-Evans rats. Both groups were 

dosed with 1 mg/kg, the adults once a day for 14 days, and the neonates once every other day for 26 days. 

Adult rats became self-mutilating and highly aggressive after 10–12 days, whereas the neonates exhibited 
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3. HEALTH EFFECTS 

spontaneous tremors and seizures, and were reactive to noise but were not aggressive. The major finding 

in both groups was neuronal necrosis in the neocortex, pyriform cortex, hippocampal formation, basal 

ganglia, brain stem, spinal cord, and dorsal root ganglia. The neurons of the hippocampal formation and 

pyriform cortex were most vulnerable to the effects of trimethyltin. Bouldin et al. (1981) also observed 

that acute high doses affected preferentially neurons of the fascia dentata, whereas longer-term low doses 

affected the neurons of Ammon’s horn. Ultrastructurally, the changes were characterized by cytoplasmic 

accumulations of dense-core vesicles and tubules, autophagic vacuoles, and polymorphic dense bodies 

both in acute and chronic intoxications in both mature and immature rats. Light- or electron-microscopy 

provided no evidence of neuronal necrosis in the hippocampal formation or pyriform cortex of neonatal or 

adult rats exposed to dimethyltin, diethyltin, tripropyltin, tributyltin, tricyclohexyltin, or triphenyltin 

(Bouldin et al. 1981). 

Chang et al. (1983) conducted a comparative study in two strains of rats (Long-Evans and SpragueDawley) and mice (Balb/c and C57BL/6). All groups were dosed once, mice with 3 mg/kg and rats with 

7.5 mg/kg trimethyltin chloride. Mice showed signs of intoxication earlier than rats and more prominent 

hippocampal lesions than rats. Long-Evans rats showed signs of intoxication earlier than SpragueDawley rats (3 days vs. 5 days). Furthermore, while mice showed most lesions in the hippocampal fascia 

dentata, rats showed more prominent neuronal damage in the olfactory cortex and hippocampal Ammon’s 

horn. Trimethyltin also has been shown to induce neuronal damage in sensory neurons of the central and 

peripheral nervous system (Chang and Dyer 1983). These investigators found that a single gavage dose 

of 6 mg/kg of trimethyltin chloride produced extensive damage in the retina, inner ear, pyriform cortex, 

olfactory tubercle, and dorsal root ganglia of rats. Inner ear damage was already evident 72 hours after 

dosing and extensive destruction was apparent 15–30 days after treatment. Small neurons in the olfactory 

cortex (pyriform cortex and olfactory tubercle) also degenerated rapidly after treatment with trimethyltin. 

Fifteen days after exposure, there was extensive destruction of the pyriform cortex and olfactory cortex. 

No necrotic changes were seen in the dorsal root ganglia, but electron microscopy showed accumulation 

of lysosomes and formation of myeloid bodies both in the cell bodies and axons. Hypertrophy and 

hyperplasia of the neuronal mitochondria were seen 30 days after treatment; these changes were thought 

to represent a compensatory response. 

The neurological effects of trimethyltin also have been studied in other species. Brown et al. (1984) 

conducted studies with trimethyltin chloride in hamsters, marmosets, and gerbils. Hamsters receiving a 

single dose of 4 or 5 mg/kg showed whole-body tremors and were almost moribund when sacrificed at 

4 days. These animals showed neuronal necrosis and chromatolysis primarily in the hippocampus but 
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also in the pyriform cortex, amygdala, neocortex, and various brain stem nuclei. Motor neurons of the 

cervical spinal cord were also involved. The brains of hamsters treated with 1 mg/kg once per week for 

5 weeks were normal and those of animals treated similarly for 7 weeks showed neuronal degeneration 

confined to the hippocampus. The marmoset monkeys were gavaged with single doses (3–4.5 mg/kg) or 

two doses (3 plus 3 mg/kg or 3 plus 1.5 mg/kg) of trimethyltin chloride. Signs of poisoning at 24 hours 

included fine tremor, diarrhea, and salivation. Two days later, these signs increased to whole body 

tremor, ataxia, agitation, aggression, and loss of appetite. A dose of 3.75 mg/kg caused prostration at 2– 

3 days with continuous body tremors and myoclonic jerks of the head and body. No convulsions were 

seen. One monkey at 3 mg/kg was moribund on day 4, four at 3.75 mg/kg on days 2–3, and one at 

4.5 mg/kg on day 1. Two monkeys given 3 mg/kg survived to days 35 and 45. The monkeys that died 

early showed neuronal necrosis and chromatolysis primarily in the hippocampus but also in the pyriform 

cortex, amygdala, neocortex, various brain stem nuclei, and retina. Some signs of histopathological 

alterations were still present in the two monkeys that survived 35 and 45 days. No lesions were seen in 

the lumbar spinal ganglia or sciatic nerve. Gerbils were gavaged with single doses between 3 and 

12 mg/kg of trimethyltin chloride. All dose levels caused lethality. Clinical signs included whole body 

tremors, prostration, and convulsions. Histopathologic examinations showed neuronal necrosis and 

chromatolysis primarily in the hippocampus but also in the pyriform cortex, amygdala, neocortex, and 

various brain stem nuclei. In two animals given 3 mg/kg that survived to 7 and 18 days, the pyramidal 

cells in the hippocampus were normal. 

Less information is available for other organotins. For example, Wistar rats treated once with 6.3 mg 

tributyltin chloride/kg (the lowest dose level tested) showed no overt signs of toxicity (Ema et al. 1991a). 

Diurnal activity was higher than in controls on days 1–4 in the groups receiving the highest dose 

(50 mg/kg). Spontaneous motor activity during the dark phase was significantly decreased, but returned 

to normal 4 days after dosing. Also, the acquisition of conditioned avoidance responses was significantly 

impaired at 25 mg/kg. An additional acute study reported that a daily dose of 2.5 mg tributyltin 

bromide/kg for 6 days induced slight tremors and weakness in Sprague-Dawley rats; doses of 1.5 mg/kg 

caused no adverse effects (Yallapragada et al. 1991). Administration of 37.5 or 75 mg tributyltin 

oxide/kg/day for 3 days to rats induced significant reductions in serotonin, dopamine, and noradrenaline 

in whole brain preparations (Elsabbagh et al. 2002). In general, the reductions were dose-related. 

ATPase activities also were significantly reduced. Histopathological examination of the brains showed 

hyperemic meningeal and cerebral blood vessels. There were focal hemorrhages in vacuolated 

myelinated fibers and some neurones showed chromatolysis and others necrosis. The purkinje cells 

showed degenerative changes. In general, the severity of the effects was dose-related. In a 2-year 
 

TIN AND TIN COMPOUNDS 140 

3. HEALTH EFFECTS 

bioassay with tributyltin oxide, no histopathologic alterations were observed in the brain and spinal cord 

from Wistar rats administered dietary doses of up to 2.5 mg/kg/day (Wester et al. 1990). 

Rats treated acutely with 20 mg dibutyltin laureate/kg/day for 3 days showed decreased motor activity 

and learning, but that dose also caused lethality (Alam et al. 1993). In 78-weeks dietary studies with 

dibutyltin chloride, there was no evidence of adverse gross or microscopic alterations in the brains of 

Fischer-344 rats and B6C3F1 mice dosed with up 6.7 and 19.8 mg/kg/day, respectively (NCI 1978a). No 

neurological effects have been observed in chronic-duration studies with triphenyltin hydroxide in rats 

and mice (NCI 1978b), and dogs (Sachsse et al. 1987). 

The highest NOAEL values and all reliable LOAEL values for neurological effects in each species and 

duration category are recorded in Tables 3-3 through 3-8 and plotted in Figures 3-3 through 3-8 for 

organotin compounds. 

3.2.2.5 Reproductive Effects 

Inorganic Tin Compounds. No studies were located regarding reproductive effects in humans after oral 

exposure to inorganic tin compounds. 

Limited information was found on effects in animals. No reproductive effects (number of corpora lutea 

and of implantation and resorption sites) were reported in rats, mice, and hamsters administered up to 

31 mg tin/kg/day (as stannous chloride) during gestation (Gds 6–15 for rats and mice, Gds 6–10 for 

hamsters) (FDA 1972). Exposure of rats during Gds 0–20 to up to approximately 45 mg tin/kg/day (as 

sodium pentachlorostannite) or 56 mg tin/kg/day (as tin fluoride) in the diet had no significant effect on 

the number of resorptions or placental weight (Theuer et al. 1971). In a 13-week study in rats, dietary 

levels ranging from 1.5 to 9.2 mg tin/kg/day as stannous chloride caused testicular degeneration 

(De Groot et al. 1973). Histopathological degeneration was seen in a few animals that were treated for 

9 weeks with 315 mg/kg/day and then sacrificed because of their moribund physiological state. The 

biological significance of the findings is unclear. 

Organotin Compounds. No studies were located regarding reproductive effects in humans after oral 

exposure to organotin compounds. 
TIN AND TIN COMPOUNDS 141 

3. HEALTH EFFECTS 

The reproductive effects of some organotin compounds have been studied mostly in rats, although some 

information in mice is also available. In most studies in rats, the pregnant dams were dosed at various 

times during pregnancy and sacrifices were conducted on Gd 20. Treatment of pregnant Wistar rats with 

doses of 7.5 mg dibutyltin dichloride/kg/day on Gds 7–15 significantly increased the number of 

resorptions and dead fetuses per litter and the percentage of postimplantation loss (Ema et al. 1991b). 

These dose levels also caused rats mortality. Doses of 5 mg/kg/day produced no significant maternal or 

reproductive effects. In a similar study, doses of 15 mg dibutyltin diacetate/kg/day administered on Gds 

7–17 significantly increased the incidence of dead or resorbed fetuses, but a lower dose of 10 mg/kg/day 

was without significant reproductive effects (Noda et al. 1992). Maternal thymus weight was reduced by 

54% with a dose of 5 mg/kg/day and body weight was significantly reduced at 15 mg/kg/day, suggesting 

that the adverse reproductive effects observed at 15 mg/kg/day may have been secondary to maternal 

toxicity and that thymic involution, while a sensitive index of maternal toxicity, may be unrelated to the 

manifestation of reproductive effects. In a more recent study with dibutyltin dichloride administered on 

Gds 6–15, the highest dose tested, 10 mg/kg/day, was maternally toxic (reduced weight gain and food 

consumption), but did not significantly affect any reproductive parameter, (i.e., total implantations, mean 

implantations/litter, total early resorptions, mean early resorptions/litter, total late resorptions, and mean 

late resorptions/litter) (Farr et al. 2001). Further studies of Ema and coworkers showed that administration of dibutyltin dichloride on Gds 7–9 induced more resorptions and postimplantation losses than 

when given on Gds 10–12 or 13–15 (Ema et al. 1992). Furthermore, within that 3-day period, Gd 8 was 

the day of highest susceptibility. Treating rats with 3.8 mg dibutyltin chloride/kg/day on Gds 4– 

7 significantly increased the percentage of postimplantation losses/litter and doses of 7.6 mg/kg/day on 

Gds 0–3 increased the number and percentage of preimplantation losses (Ema and Harazono 2000). In a 

subsequent study, Ema et al. (2003) reported that subcutaneous administration of progesterone partially 

prevented the preimplantation losses induced by dibutyltin and hypothesized that a decline in 

progesterone is a primary mechanism for the implantation failure induced by dibutyltin. Results from 

further studies by the same group of investigators suggested that the early embryonic loss induced by 

dibutyltin is due to inhibition of uterine decidualization, which is caused by inhibition of the development 

of uterine sensitivity due to decreased serum progesterone levels (Harazono and Ema 2003). 

In long-term studies, female Fischer-344 rats fed diets that provided approximately 3.33 and 

6.65 mg/kg/day dibutyltin diacetate showed inflammation and hyperplasia of the uterus (NCI 1978a). 

The frequency with which these changes were observed was greater in the low-dose group than in the 

high-dose group. However, the tissues from 17 of the 50 high-dose group animals were lost before 
TIN AND TIN COMPOUNDS 142 

3. HEALTH EFFECTS 

microscopic examination; therefore, these findings must be regarded as inconclusive. No significant 

alterations in reproductive organs from B6C3F1 mice were seen in a 78-week bioassay (NCI 1978a). 

Studies with tributyltins have provided results similar to those with dibutyltins. Increased fetal deaths and 

resorptions were seen in rats dosed with 16 mg tributyltin acetate/kg/day on Gds 7–17 (Noda et al. 

1991a); this dose levels also caused maternal toxicity (reduced food consumption and body weight gain 

and 28% reduction in thymus weight). A significant increase in resorptions and in the incidence of 

postimplantation loss was seen in rats dosed with 25 mg tributyltin chloride/kg/day (the lowest dose 

tested) on Gds 7–9 relative to controls and to treatments on Gds 10–12 or 13–15 (Ema et al. 1995b). In a 

subsequent study from the same group, Gd 9 was identified as the most susceptible for postimplantation 

loss to occur compared to Gds 7, 8, 10–15 (Ema et al. 1997a). In another study, a significant increase in 

pregnancy failure occurred when dosing with 16.3 mg/kg/day on Gds 0–3, whereas a much higher dose, 

65.1 mg/kg/day, was needed to cause pregnancy failure if treatment was done on Gds 4–7 (Harazono et 

al. 1998). A more recent study reported decreased fertility, increased postimplantation loss, and 

decreased litter size in rats treated with 20 mg tributyltin chloride/kg/day on Gds 0–19; no such effects 

were seen at 10 mg/kg/day (Adeeko et al. 2003). 

In four studies of similar design in mice (treatment for at least 10 days during gestation) (Baroncelli et al. 

1990, 1995; Davis et al. 1987; Faqi et al. 1997), the LOAEL for tributyltins was 5 mg/kg/day for 

increased early parturitions and resorptions (Baroncelli et al. 1995). A study that evaluated a different 

type of reproductive parameter showed that treatment of male ICR mice with 10 mg tributyltin oxide/kg 

2 times/week for 4 weeks significantly reduced sperm counts to about 70% of controls (Kumasaka et al. 

2002). In addition, light microscopy of the testis revealed disorganized seminiferous tubules with 

vacuolization of Sertoli cells and some loss of germ cells. No effects were seen on spermatogonia, 

spermatocytes, spermatids, Leydig cells, and the basement membrane of the seminiferous tubules; the 

study NOAEL was 2 mg/kg/day. 

Daily administration of tributyltin chloride (5–20 mg/kg/day) to 35-day-old male rats did not significantly 

alter the weights of the testes, epididymis, or prostate, but doses of 10 and 20 mg/kg/day significantly 

decreased seminal vesicle weight in a dose-related manner (Yu et al. 2003a). Doses of 10 and 

20 mg/kg/day did not produce morphological alterations in the testes or prostate, but did so in seminal 

vesicles and epididymis. In rats that underwent the same treatment but were examined 5 weeks after the 

last dose, the 20 mg/kg/day dose of tributyltin chloride significantly reduced sperm counts recovered from 

the testes relative to controls (Yu et al. 2003b). Epididymal sperm counts also were significantly reduced 
TIN AND TIN COMPOUNDS 143 

3. HEALTH EFFECTS 

at 10 and 20 mg/kg/day. In general, sperm motility was not significantly altered by treatment with 

tributyltin. 

In 2-generation reproductive studies with tributyltin chloride in male and female Wistar rats, the highest 

dose tested, 10 mg/kg/day, had no significant effect on the fertility index of females (females with 

delivery/females copulated) of either the parental generation (P) or the F1 generation (Ogata et al. 2001) 

or on the copulation index or the fertility index of F1 males (Omura et al. 2001). In a 2-year bioassay with 

tributyltin oxide in Wistar rats, no histopathological alterations were observed in the ovaries, uterus, 

testis, or prostate (Wester et al. 1990). 

Studies with triphenyltins in which pregnant rats were dosed during most of the pregnancy (Gd 5–17) 

reported significant increases in resorptions at dose levels of 13 mg/kg/day (only dose level tested) 

(Chernoff et al. 1990) and 6 mg/kg/day (Noda et al. 1991b); a NOAEL of 3 mg/kg/day was identified in 

the latter study. Dosing rats with 4.7 mg/kg/day on Gds 0–3 induced pregnancy failure, preimplantation 

loss and a decrease in the number of implantations per female (Ema et al. 1997b). However, pregnancy 

failure occurred only at 12.5 mg/kg/day and increased implantations losses only at 25 mg/kg/day when 

the rats were treated on Gds 4–6. It was suggested that preimplantation losses are caused by changes in 

the development of uterine receptivity induced by triphenyltin (Ema et al. 1999b). Similar to findings 

with other alkyltins, the most vulnerable dosing period for resorptions and postimplantation losses to 

occur was Gds 7–9 relative to Gds 10–12 or 13–15 (Ema et al. 1999a). Transient reduced fertility was 

reported in male rats treated with approximately 5 mg triphenyltin hydroxide/kg/day for up to 64 days 

(Gaines and Kimbrough 1968). However, because changes in food consumption closely followed the 

gradual change in fertility and the recovery, it appeared that the decrease in food intake was responsible 

for the reduced fertility. 

Male rats fed triphenyltin hydroxide at doses of 5.2 mg/kg/day for 2 years displayed a dose-related 

increase in Leydig cell hyperplasia (p<0.0005) and tubular atrophy (p=0.004) of the testes (Tennekes 

et al. 1989b), which was not seen in either rats dosed with up to 9.8 mg/kg/day or mice dosed with up to 

3.75 mg/kg/day for 78 weeks (NCI 1978b). Administration of up to 0.62 mg triphenyltin 

hydroxide/kg/day in the diet for up to 52 weeks to male and female dogs did not produce any significant 

gross or microscopic changes in the reproductive organs (Sachsse et al. 1987). 

The effects of diphenyltin also have been studied. Administration of t16.5 mg diphenyltin 

dichloride/kg/day on Gds 0–3 to rats significantly increased the incidence of pre-implantation losses and 
 

 

TIN AND TIN COMPOUNDS 144 

3. HEALTH EFFECTS 

24.8 mg/kg/day also decreased the pregnancy rate (Ema et al. 1999c). Results from a subsequent study 

showed that the early pregnancy failure was due to suppressed uterine decidualization and reduced serum 

progesterone levels (Ema and Miyawaki 2002). 

No significant alterations in reproductive parameters were observed in rats treated with up to 400 mg 

monobutyltin trichloride/kg/day on Gds 7–17 (Noda et al. 1992b). 

The highest NOAEL values and all reliable LOAEL values for reproductive effects in each species and 

duration are recorded in Tables 3-3 through 3-8 and plotted in Figures 3-3 through 3-8 for organotin 

compounds. 

3.2.2.6 Developmental Effects 

Inorganic Tin Compounds. No studies were located regarding developmental effects in humans after 

oral exposure to inorganic tin compounds. 

Limited information is available from studies in animals. Treatment of rats, mice, and hamsters with up 

to 31 mg tin/kg/day by gavage in water during gestation (Gds 6–15 for mice and rats, Gds 6–10 for 

hamsters) has no significant effect on fetal weight, the number of live of dead fetuses, and the incidence 

of external and internal malformations (FDA 1972). Administration of up to approximately 56 mg 

tin/kg/day (as tin fluoride) or 45 mg tin/kg/day (as sodium pentachlorostannite) to rats on Gds 0–20 had 

no significant effect on average fetal weight or the number of live fetuses per litter (Theuer et al. 1971). 

Organotin Compounds. No studies were located regarding developmental effects in humans after oral 

exposure to organotin compounds. 

Several organotins have been evaluated for potential developmental effects in animals. A dose of 5 mg 

dibutyltin dichloride/kg/day administered by gavage to pregnant Wistar rats on Gds 7–15 significantly 

increased the incidence of external and skeletal malformations but not of internal malformations (Ema et 

al. 1991b). Cleft jaw and ankyloglossia were the most frequent malformations. A lower dose of 

2.5 mg/kg/day did not cause any significant effect. Since adjusted maternal weight and food consumption 

during pregnancy were not affected at 5 mg/kg/day, it would appear that the developmental effects 

occurred in the absence of maternal toxicity. In a similar study in Wistar rats dosed on Gds 7–17, Noda et 

al. (1992) observed increased external and skeletal malformations at 10 mg/kg/day, but not at 
 

TIN AND TIN COMPOUNDS 145 

3. HEALTH EFFECTS 

5 mg/kg/day. Neither maternal weight not food consumption were significantly altered at 10 mg/kg/day, 

but maternal thymus weight was significantly reduced at 5 mg/kg/day suggesting that for dibutyltin, a 

known immunotoxicant (see Section 3.2.2.3), maternal changes in thymus weight may be a better 

predictor of embryotoxicity and teratogenicity than changes in body weight. In a third study of similar 

design, Farr et al. (2001) observed a slight increase in malformations at 10 mg/kg/day, a dose level that 

also reduced maternal weight gain and food consumption, and decreased thymus weight; 5 mg/kg/day 

was the maternal and developmental NOAEL. 

Studies have been conducted to determine the period of highest susceptibility during gestation. For 

example, Ema et al. (1992) dosed rats with dibutyltin dichloride (20 mg/kg/day) at various times during 

gestation, after Gd 6, and noticed that the highest incidence of malformations occurred when dosing on 

Gd 8. No teratogenicity was evident when the rats were treated on Gds 10–12 or 13–15. Fetal weights 

were most severely decreased when dosing on Gds 7–9. In a more recent study, Ema and Harazono 

(2000) reported that doses of up to 15.2 mg dibutyltin dichloride/kg/day administered on either Gds 0– 

3 or 4–7 caused no external malformations. 

Doses of 16 mg tributyltin acetate/kg/day administered to pregnant Wistar rats on Gds 7–17 significantly 

increased the incidence of external malformations, particularly cleft palate and also reduced maternal 

weight gain and food consumption, and thymus weight by about 28% (Noda et al. 1991a). The 

developmental NOAEL was 8 mg/kg/day, but even a lower dose, 4 mg/kg/day, reduced maternal thymus 

weight. A dose of 25 mg tributyltin chloride/kg/day administered on Gds 13–15 caused more external 

malformations in rats (particularly cleft palate) than when given on Gds 10–12 (Ema et al. 1995b). 

Single-day treatments from Gd 7 onward showed that the most vulnerable periods for increased external 

malformations were Gds 11, 12, 13, and 14; a smaller increase also occurred when dosing on Gd 8 (Ema 

et al. 1997a). As with dibutyltin, doses of up to 16.3 mg tributyltin chloride administered on Gds 0–3 or 

4–7 did not cause malformations (Harazono et al. 1998). Doses of tributyltin chloride up to 10 mg/kg/day 

administered on Gds 8–19 did not significantly affect fetal weight, anogenital distance (male and female 

pups), or sex ratio, and caused no external malformations (Adeeko et al. 2003). However, 

0.25 mg/kg/day and higher doses given on Gds 0–19 significantly increased anogenital distance in male 

pups and t10 mg/kg/day increased the percentage of unfused ossification centers in the sternebrae 

(Adeeko et al. 2003). 

In a 2-generation reproductive toxicity study in female Wistar rats designed to examine the reproductive 

effects of tributyltin chloride (0.4, 2, 10 mg/kg/day), exposure to the highest dose (10 mg/kg/day) 
 

TIN AND TIN COMPOUNDS 146 

3. HEALTH EFFECTS 

significantly decreased the percentage of live pups and the birth weight of female pups (Ogata et al. 

2001). Gestational body weight was significantly reduced in the high-dose parental (P) and F1 

generations. There were no gross malformations. The day of eye opening was significantly delayed in 

the high-dose F2 pups. Body weights of F1 and F2 high-dose pups were significantly lower than controls 

for both pre- and postweaning. Anogenital distance was significantly increased in F1 and F2 females on 

postnatal days (Pnds) 1 and 4 with the high-dose and on Pnd 1 in mid-dose F1. The day of vaginal 

opening was significantly delayed (6 days) in the high-dose F1 and F2 groups. Analysis of the estrous 

cycles between Pnds 71 and 92 showed no alterations in F1, but the number of cycles was significantly 

decreased in the high-dose F2. Also, the percentage of normal cycles was decreased in the high-dose F1 

and F2 rats. The NOAEL was 2 mg/kg/day. 

A study of similar design was conducted to evaluate the development of reproductive parameters in male 

Wistar rats (Omura et al. 2001). The doses tested were 0.4, 2, and 10 mg/kg/day. Body weight was 

significantly reduced in the high-dose F1 pups on Pnds 1, 4, 14, and 21 and in the mid-dose F1 pups on 

Pnds 14 and 21. Body weight was also reduced in the high-dose F2 pups on Pnds 1, 4, 14, and 21. 

Anogenital distance and day of testes descent (measured on Pnds 1 and 4) was not significantly altered in 

F1 or F2 males. The day of eye opening was significantly delayed in the mid- and high-dose F1 males and 

in the high-dose F2 pups. Postnatal body weight gain, but not food consumption, was significantly 

depressed in the high-dose F1 and F2 pups. Effects on the weight of the sex organs included: decreased 

absolute testis weight in all F1 groups (dose-related); decrease absolute epididymis weight in the low- and 

high-dose F1 groups; decrease absolute testis and epididymis weight in the high-dose F2 groups and in 

relative prostate weight in the mid- and high-dose F2 groups. The only sperm parameters that were 

significantly altered were sperm count in the high-dose F2 rats and spermatid count in high-dose F1 rats 

and the mid- and high-dose F2 rats. Histological examination of the testes revealed minimal alterations in 

the high-dose F1 groups, but more frequent and severe effects in F2 groups, which were considered 

abnormal and consisted of vacuolization of the seminiferous epithelium, spermatid retention, and delayed 

spermiation. Serum testosterone was increased and estradiol was decreased in the high-dose F1; serum 

estradiol was decreased, and luteinizing hormone (LH) was increased in the high-dose F2. Based on 

decreased pups weight on Pnds 14 and 21, the authors established the developmental LOAEL at 

2 mg/kg/day and the NOAEL at 0.4 mg/kg/day. The changes in sex organ weight were not considered 

biologically significant. 

Tributyltin chloride has also been shown to cause neurodevelopmental effects in rats. Treatment of 

pregnant Sprague-Dawley rats with 1 mg/kg/day (the lowest dose tested) on Gds 6–20 caused 
 

TIN AND TIN COMPOUNDS 147 

3. HEALTH EFFECTS 

hyperactivity in the offspring when tested on Pnds 60–70 and impaired learning in a radial arm maze test 

on Pnds 65–68 (Gardlung et al. 1991). No obvious maternal toxicity was noticed and there were effects 

on the physical development of the offspring. No significant effects were seen on open-field activity 

(Pnds 120–125) or on performance on a swim-maze test (Pnds 66–70). Also, in rats sacrificed on Pnds 

60–70, no significant alterations were found in the levels of noradrenaline in the frontal and occipital 

cortex, hippocampal formation, and cerebellum; levels of serotonin and metabolites in the frontal cortex, 

striatum, olfactory tubules, hippocampus, mesencephalon, and cerebellum; and levels of dopamine and its 

metabolites in the striatum, olfactory tubules, and mesencephalon. Trihexyltin chloride, which was also 

tested in the study, was much less effective than tributyltin. 

Cooke et al. (2004) and Tryphonas et al. (2004) evaluated systemic and immunological parameters in rats 

that were exposed to tributyltin chloride in utero (Gds 8–21), through the mother’s milk, and directly as 

young adults until the age of 90 days. The doses tested were 0.025, 0.25, and 2.5 mg/kg/day. Neither 

body weights nor food consumption was affected in the dams. No effects were observed on litter size, 

pup's weight at birth, sex ratio, or survival until weaning. Growth of the treated pups after weaning was 

slightly reduced (<10%) relative to controls and analysis of food consumption and weight gain showed 

that male pups converted feed into weight gain less effectively than females. No effects were seen on the 

weights of pup's brain, kidney or adrenals, but there was a decrease in absolute and relative liver weight 

in 60-day-old females at 0.025 and 2.5 mg/kg/day, a decrease in absolute and relative liver weight in 

90-day-old males at 2.5 mg/kg/day, decrease in absolute spleen weight in 30-day-old males at 

2.5 mg/kg/day and in relative spleen weight in 60-day-old females at 2.5 mg/kg/day, a decrease in relative 

thymus weight in 60-day-old females at 0.25 and 2.5 mg/kg/day and in absolute thymus weight in 30-dayold males at 2.5 mg/kg/day. No consistent treatment-related gross or microscopic lesions were observed 

in dams and pups. Clinical chemistry changes of potential biological importance included a decrease in 

serum amylase in 90-day-old males at 0.25 and 2.5 mg/kg/day and decreased T4 also in 90-day-old males 

at 2.5 mg/kg/day. Based on the changes in pup's organ weights and in clinical chemistry parameters, the 

0.25 mg/kg/day dose is a LOAEL and 0.025 mg/kg/day a NOAEL. The reduced weight gain of the pups 

is not considered adverse because the difference with controls was less than 10%. 

In the study of immunological parameters (Tryphonas et al. 2004), the only significant change in serum 

immunoglobulin levels that appeared dose-related was an increase in IgG at 0.25 and 2.5 mg/kg/day in 

90-day old males. Flow cytometric analysis of splenocytes showed a significant increase mean percent 

and absolute NK cell numbers in high-dose 30-day-old males and females, a decrease in the percentage, 

but not in absolute numbers of CD4+8+ T cells in 60-day old females, and an increase in the percentage 
TIN AND TIN COMPOUNDS 148 

3. HEALTH EFFECTS 

of NK cells in 90-day-old males. The anti-SRBC IgM response was not affected by exposure to 

tributyltin. No significant alterations were observed in the lymphoproliferative activity of splenocytes in 

response to mitogen stimulation. The delayed-type hypersensitivity response (DTH) was not affected in 

60-day-old females, but 90-day-old males showed a significant trend toward a decrease in DTH response 

with increasing dosis of tributyltin. The assays for L. monocytogenes infectivity and NK cell activity did 

not give dose-related responses. Cytokine levels in serum were not affected. Gross examination of 

lymphoid tissues was unremarkable. The most consistent histological finding was mild to moderate 

cortical atrophy of the thymus, characterized by decreased numbers of cortical lymphocytes at 

2.5 mg/kg/day at all ages. 

In mice, doses of 11.7 mg tributyltin oxide/kg/day on Gds 6–15 induced cleft palate and other bone 

abnormalities and also decreased weight gain in the pregnant mice (Davis et al. 1987). Similar findings 

were reported by Faqi et al. (1997) following dosing the mice on Gds 6–17 with 27 mg/kg/day, a dose 

level that also caused maternal toxicity. The developmental and maternal NOAEL was 13.5 mg/kg/day. 

Doses of up to 20 mg tributyltin oxide/kg/day did not increase the incidence of malformations in pups 

from dams treated on Gds 6–15, but significant early pup mortality occurred with this dose level 

(Baroncelli et al. 1995). That same dose level did not significantly alter hematological parameters in the 

dams, neonates, or pups on Pnds 7, 14, and 21 (Karrer et al. 1995). Absolute and relative thymus weight 

was reduced in pups on Pnd 7 and increased on Pnd 21 relative to controls; spleen weight was not 

affected by treatment. 

Experiments conducted with triphenyltin chloride in Wistar rats showed that doses of up to 

12.5 mg/kg/day administered on either Gds 7–9, 10–12, or 13–15 did not significantly increase the 

incidence of malformations, but fetal weight was decreased at 9.4 mg/kg/day when dosed on Gds 13– 

15 (Ema et al. 1999a). No significant effect was seen on the incidence of malformations in doses up to 

25 mg/kg/day administered on Gds 4–6 or up to 6.3 mg/kg/day on Gds 0–3; fetal weight was decreased 

with doses of 4.7 mg/kg/day administered on Gds 0–3 (Ema et al. 1997b). An unpublished study reported 

that fetal weights were slightly depressed (11%) in the offspring of New Zealand white rabbits that were 

administered 0.9 mg triphenyltin hydroxide/kg/day by gavage on Gds 6–18 (Rodwell 1987). Delayed 

ossification of the hyoid bone was also present, but there were no teratogenic effects. Food consumption 

and maternal weight gain were also significantly reduced at this dose level. The maternal and 

developmental NOAEL was 0.3 mg/kg/day. No other study in rabbits was identified that could have been 

used to corroborate or refute these findings. 
TIN AND TIN COMPOUNDS 149 

3. HEALTH EFFECTS 

In a study with diphenyltin dichloride, treatment of rats with 16.5 mg/kg/day and higher doses on Gds 0–3 

significantly decreased the body weight of the live fetuses, but no significant effect was seen with doses 

of 8.3 mg/kg/day (Ema et al.1999c). Treatment with up to 33 mg/kg/day did not alter the sex ratio or 

induce external malformations. 

Monobutyltin trichloride did not induce maternal or developmental effects in rats administered the 

compound on Gds 7–17 in doses of up to 400 mg/kg/day (Noda et al. 1992). 

Trimethyltin chloride (0.05, 0.16, 0.34 mg/kg/day) altered extinction learning ability in 11-day-old rat 

pups from rats treated for a period that included 14 days premating, gestation, and lactation (Noland et al. 

1982). This specific effect (altered extinction learning ability) was dose-related, but no dose-response 

was evident for other behavioral tests. Tests with monomethyltin trichloride (3.7, 12.5, and 

37 mg/kg/day) were inconclusive. 

All reliable NOAEL and LOAEL values for developmental effects in each species and duration category 

are recorded in Tables 3-3 through 3-8 are plotted in Figures 3-3 through 3-8 for organotin compounds. 

3.2.2.7 Cancer 

Inorganic Tin Compounds. No studies were located regarding cancer effects in humans after oral 

exposure to inorganic tin compounds. 

A carcinogenesis bioassay for stannous chloride was conducted in male and female Fischer-344 rats and 

B6C3F1/N mice (NTP 1982). Diets containing 32 or 63 mg tin/kg/day as stannous chloride were fed to 

rats and 82 or 164 mg tin/kg/day to mice for 105 weeks. Aspects of the toxicity of stannous chloride 

observed during prechronic studies completed prior to the bioassay have been presented in 

Sections 3.2.2.1 and 3.2.2.2. Tumors occurred at increased incidences in the dosed groups in the 

bioassay. These included C-cell adenomas of the thyroid in low-dose male rats, lung adenomas in the 

high-dose male rats, and hepatocellular adenomas and carcinomas and histiocytic lymphomas in both 

low- and high-dose female mice. However, the authors concluded that the incidences of the tumors 

relative to the histological control rat and mouse data were similar and were not clearly related to 

administration of stannous chloride. The possibility that the C-cell tumors in the thyroid may have been 

related to stannous chloride feeding was not ruled out since the incidence in the low-dose group, but not 

the high-dose group, was significant by comparison to the controls and to historical controls. Despite the 
TIN AND TIN COMPOUNDS 150 

3. HEALTH EFFECTS 

reservation, the conclusion from the NTP (1982) data was that stannous chloride was not carcinogenic for 

male or female rats or mice. 

An earlier chronic oral study that evaluated the carcinogenic potential of sodium chlorostannate must be 

regarded as flawed for several reasons. The rats were fed on irregular dose schedules and most of the 

animals developed pneumonia (Roe et al. 1965). After 1 year, three malignant tumors were identified in 

30 rats. Long-term chronic studies of stannous chloride in rats and mice were conducted using a single 

low-dose exposure and limited pathology studies (Schroeder and Balassa 1967; Schroeder et al. 1968). 

The authors concluded that stannous chloride was not carcinogenic. 

Organotin Compounds. No studies were located regarding cancer effects in humans after oral exposure 

to organotin compounds. 

A carcinogenesis bioassay for dibutyltin diacetate was conducted in male and female Fischer-344 rats and 

B6C3F1 mice (NCI 1978a). Rats were fed diets that provided approximately 0, 3.33, or 6.65 mg 

dibutyltin diacetate/kg/day for 78 weeks followed by a period of no compound administration for 

26 weeks. Mice also were fed diets that provided approximately 0, 9.9, or 19.8 mg/kg/day for 78 weeks 

followed by a period of no compound administration for 14 weeks. There were no significant increased 

tumor incidence in treated groups of rats and mice compared to their respective controls. However, 

accidental loss of tissues from the uterus from 17 of the 50 high-dose female rats precluded a complete 

evaluation of neoplasms in this organ. Apparently, there were no historical control data available at the 

time for evaluation of background versus experimental findings. The general conclusion was that 

dibutyltin diacetate was not carcinogenic for male rats and male or female mice under the experimental 

conditions of the study. The loss of the tissues prevented reaching a conclusion with regard to the 

relationship between dibutyltin diacelate and the occurrence of uterine neoplasms in female rats. 

Another organotin compound, triphenyltin hydroxide, was tested in a bioassay using male and female 

Fischer-344 rats and B6C3F1 mice (NCI 1978b). The regimen included dietary feeding for 78 weeks 

followed by a 26-week observation period. Dosage levels were approximately 0, 1.88, and 

3.75 mg/kg/day as triphenyltin hydroxide for rats and 0, 4.88, and 9.75 mg/kg/day for mice. Survival was 

affected in male mice, but no other effects were observed in the mice or the rats. The incidence of tumors 

seen in treated animals was comparable to controls. Historical control data were apparently not available 

at the time for evaluation of background versus experimental findings. The general conclusion was that 
TIN AND TIN COMPOUNDS 151 

3. HEALTH EFFECTS 

triphenyltin hydroxide was not carcinogenic for male and female rats and mice under the experimental 

conditions of the study. 

In contrast to these results, longer-term studies on the carcinogenicity of triphenyltin hydroxide in Wistar 

rats and NMRI mice, using higher maximum doses, produced tumors in both species (Tennekes et al. 

1989a, 1989b). In rats administered doses of 0.3–6.2 mg/kg/day triphenyltin hydroxide in the diet, there 

was a dose-related increase in pituitary adenomas in the exposed females at 104 weeks. Although the 

incidence of this lesion was high in the control animals (64.4%), it was even greater in the exposed 

animals, especially at the two highest dose levels (76.8 and 93.1%, respectively). There was also a doserelated decrease in survival for the females that was related to tumor incidence. Only 23% of the females 

receiving the highest dose were alive at the termination of the study as opposed to 80% of the males. 

The number of males with testicular Leydig cell tumors was increased in animals exposed to 

5.2 mg/kg/day triphenyltin hydroxide for 104 weeks (16.7 as opposed to 1.7% in the controls). 

Tumors were also present in mice given diets containing 0.9–20.2 mg/kg/day triphenyltin hydroxide. 

After sacrifice at 80 weeks, examination of the tissue revealed an increased incidence of hepatocellular 

adenomas in both sexes. These tumors were consistent with the nodular hyperplasia seen in the livers of 

the treated animals. As was the case with the rat study, the females appeared to be more sensitive to tin 

treatment than the males. There was a decrease in survival for the females at the highest dose. Only 50% 

of the females receiving this dose were alive at the termination of the study as opposed to 70% of the 

males in the same dose group and 74% of the female control animals. The difference between the highdose treated females and control females was statistically significant. 

A 2-year bioassay was conducted with tributyltin oxide in male and female Wistar rats (Wester et al. 

1990). The rats were fed a diet that provided 0, 0.019, 0.19, or 2.1 mg/kg/day of tributyltin oxide for 

males and 0, 0.025, 0.25, or 2.5 mg/kg/day for females. In high-dose males, survival at termination was 

40 vs. 60% in controls; in females, it was 54 vs. 74% in controls. There was a significant increase in total 

pituitary tumors in males and females from the low- and high-dose groups, but not in the mid-dose 

groups. Also, the total pheochromocytomas (adrenal gland) were significantly increased in high-dose 

males and females. In addition, the number of parathyroid adenomas was significantly increased in highdose males. Wester et al. (1990) stated that the increase incidence of some tumors may have been due to 

hormonal or immunological changes. They further noted that because there is a high spontaneous 

incidence of these tumors in this strain of rat, the variable incidence in the treated groups, and the absence 
 

TIN AND TIN COMPOUNDS 152 

3. HEALTH EFFECTS 

of a dose-effect relationship, the significance of the increased incidence is questionable. Based on no 

human data and questionable data in rats, EPA (IRIS 2005) placed tributyltin oxide in Group D, not 

classifiable as to human carcinogenicity or, according to updated guidelines (EPA 2003g), in a group for 

which there is inadequate information to assess carcinogenic potential. 

3.2.3 Dermal Exposure 

Except for dermal/ocular effects (Section 3.2.3.2) there is no information that describes health effects in 

humans or animals after dermal exposure to inorganic tin or organotin compounds. Table 3-9 summarizes 

available quantitative information on health effects that have been observed in animals after dermal 

exposure to organotin compounds. 

3.2.3.1 Death 

Inorganic Tin Compounds. No studies were located regarding death in humans or animals after dermal 

exposure to inorganic tin compounds. 

Organotin Compounds. The death of a female worker accidentally drenched in phenyltin and other 

unidentified compounds was described in Section 3.2.1.1. Second and third degree burns developed 

12 hours following the accident (NIOSH 1976). 

Dermal LD50 values in animals are available for a number of organotin compounds (Smith 1978). A 

dermal LD50 in rabbits was reported to be 11,700 mg/kg bis(tributyltin) oxide (Elsea and Paynter 1958). 

For rats, an LD50 of 605 mg/kg is given (Smith 1978). Despite variations in values for other compounds 

such as benzoates, naphthenates, and fluorides, the acute dermal toxicity of organotin compounds is 

generally less than by the oral route. The LD50 values for representative species in the acute- and 

intermediate-duration category are recorded in Table 3-9. Doses are expressed as mg/kg/day of the 

compounds rather than as doses of tin. 
242

mg/kg/day

242

243

mg/kg/day

243

2044

mg/kg mg/kg

2044

2045

%volume

2045

245 mg/kg/day

245

244

mg/kg/day

244

153 

Table 3-9 Levels of Significant Exposure to Tributyltins - Dermal 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) 

ACUTE EXPOSURE 

Death 

(albino) 

Rat 1 d 

1x/d 

System NOAEL Less Serious 

LOAEL 

605 

mg/kg/day 

Serious 

(LD50) 

Reference 

Chemical Form 

Smith 1978 

TBT 

(albino) 

Rabbit once 11700 

mg/kg/day 

(LD50) Elsea and Paynter 1958 

TBT 

Systemic 

(BALB/c) 

Mouse 

(C) 

once Dermal 0.9 F 

mg/kg 

1.8 F 

mg/kg 

(skin irritation) Corsini et al. 1996 

TBT 

Immuno/ Lymphoret 

(BALB/c) 

Mouse 

(C) 

once 0.25 F 

%volume 

(contact sensitization) Stringer et al. 1991 

TBT 

INTERMEDIATE EXPOSURE 

Death 

Gn Pig 50 d 

1x/d 40 M 

mg/kg/day 

(LD50) Mori et al 1984 

TBT 

(albino) 

Rabbit 90 d 

5 d/wk 

7 hr/d 

68 

mg/kg/day 

(7/10 animals died) Sheldon 1975 

TBT 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
246

mg/kg/day

246

mg/kg/day mg/kg/day

247

mg/kg/day

247

154 

Table 3-9 Levels of Significant Exposure to Tributyltins - Dermal (continued) 

Exposure/ LOAEL 

Duration/ 

Species Frequency Reference 

(Strain) (Route) System NOAEL Less Serious Serious Chemical Form 

Systemic 

(Hartley) 

Gn Pig 50 d 

1 x/d Renal 10 M 

mg/kg/day 

(tubule degeneration) Mori et al 1984 

TBT 

Bd Wt 10 M 

mg/kg/day 

(decreased body weight 40 M 

mg/kg/day 

(severe decrease in body 

weight) 

Rabbit 90 d 

5 d/wk 

7 hr/d 

Dermal 14 

mg/kg/day 

Sheldon 1975 

TBT 

Bd Wt = body weight; (C) = capsule; d = day(s); F = Female; (G) = gavage; Gn pig = Guinea pig; hr = hour(s); LD50 = lethal dose, 50% kill; LOAEL = lowest-observed-adverse-effect 

level; M = male; NOAEL = no-observed-adverse-effect level; x = time(s); wk = week(s) 

TIN AND TIN COMPOUNDS

 3. HEALTH EFFECTS 
 

TIN AND TIN COMPOUNDS 155 

3. HEALTH EFFECTS 

3.2.3.2 Systemic Effects 

Inorganic Tin Compounds. No studies were located regarding respiratory, cardiovascular, 

gastrointestinal, hematological, musculoskeletal, hepatic, or renal effects in humans or animals after 

dermal exposure to inorganic tin compounds. 

Organotin Compounds. No studies were located regarding respiratory, cardiovascular, gastrointestinal, 

hematological, musculoskeletal, or renal effects in humans after dermal exposure to organotin 

compounds. 

No studies were located regarding respiratory, cardiovascular, gastrointestinal, hematological, 

musculoskeletal, or hepatic effects in animals after dermal exposure to organotin compounds. 

The highest NOAEL values and reliable LOAELs are recorded in Table 3-9. 

Hepatic Effects. Signs of hepatic injury, as judged by increased serum AST and ALT activities, were 

reported in a case of acute dermal exposure to triphenyltin acetate (Colosio et al. 1991). The patient, a 

36-year-old man, spilled powder of a 19% formulation of triphenyltin acetate on exposed skin on his 

arms. The acute rise in transaminase activities was followed by a gradual decrease for the next 18 days. 

Twelve days after poisoning, echotomography showed a generalized enlargement of the liver. Three days 

later, examination of a liver needle biopsy showed slight and nonspecific inflammatory abnormalities. 

Slight hepatomegaly persisted when the patient was discharged 21 days after poisoning. 

Renal Effects. Doses of 10 or 40 mg tributyltin oxide/kg/day were applied to the shaved skin of male 

guinea pigs for 50 days (Mori et al. 1984). Swelling, degeneration, and destruction of tubular epithelium 

were observed, but there were no changes in the glomerulus. There was also an increased excretion of 

sodium, chloride, phosphate, glucose, and amino acids in the urine. In serum, the concentrations of 

phosphate and certain amino acids were low reflecting the excessive loss in the urine. According to the 

authors, these findings were consistent with a secondary Fanconi syndrome. These renal tubular changes 

are similar to those seen with inorganic tin compounds after oral exposure (see Section 3.2.2.2) and 

suggest that the compound was absorbed systemically. 
TIN AND TIN COMPOUNDS 156 

3. HEALTH EFFECTS 

Dermal Effects. 

Inorganic Tin Compounds. No studies were located regarding dermal effects in humans after dermal 

exposure to inorganic tin compounds. 

Stannous fluoride (0.25 and 0.5%) and stannous chloride (1 and 2%) produced leukocyte pustules in 

rabbit skin along the area adjacent to an abdominal epidermal scratch (Stone and Willis 1968). 

Infiltration of the tissue with polymorphonuclear and mononuclear leukocytes was present in the absence 

of pustules at a stannous chloride concentration of 0.5% and a stannous fluoride concentration of 0.1%. 

Organotin Compounds. It is known that organotins are skin irritants in humans (Sheldon 1975). Direct 

skin contact with triphenyltin fluoride produced an irritant contact folliculitis in a male worker (Andersen 

and Petri 1982). Patch tests were performed in human subjects, as well as in guinea pigs and rabbits, but 

the dermatitis could not be reproduced. An irritant contact dermatitis was also seen in workers using a 

paint containing tributyltin oxide (Goh 1985). Sensitization was not observed in any of the referenced 

studies or in a separate study of tributyltin oxide-based paints (Gammeltoft 1978). Lyle (1958) described 

the following time-course of events in five volunteers who had undiluted tributyltin chloride painted on 

the skin of the back of the hand. Reddening and swelling of the mouths of the hair follicles appeared after 

2–3 hours; this was followed by progressively intense follicular inflammation. The pruritus was confined 

to the tested area and persisted for 2 or 3 days. Pustules appeared on the second day and remained small 

until they dried up on the third or fourth day. On the fifth day, resolution was well advanced and, after a 

week, all that remained was faint punctate erythema with a little perifollicular scaling. 

Tributyltin oxide is a severe irritant to the skin in rabbits (Sheldon 1975). By contrast, tributyltin fluoride 

and triphenyltin fluoride produced only minimal skin irritation (Sheldon 1975). Other acute studies have 

likewise demonstrated the skin irritating potential of tributyltin oxide and triphenyltin acetate in rats and 

mice (Corsini et al. 1996a; Klimmer 1969; Pelikan and Cerny 1968). 

Dermal exposure of rats to doses of 80 mg/kg of dipropyltin dichloride, diisopropyltin dichloride, or 

diethyltin dichloride for 5 consecutive days produced necrosis, edema, and inflammation of the skin 

(Barnes and Stoner 1958). The same dose of dimethyltin dichloride produced dermal necrosis with black 

scar formation; dibutyltin dichloride produced little superficial damage to the skin and some edema of 

subcutaneous tissues. Dihexyltin dichloride and dioctyltin dichloride did not produce skin lesions 

(Barnes and Stoner 1958). In a 90-day repeated-dose dermal study, rabbits developed skin irritation at 
 

TIN AND TIN COMPOUNDS 157 

3. HEALTH EFFECTS 

each of three levels tested (14, 27, and 68 mg/kg/day tributyltin fluoride) (Sheldon 1975). Deaths 

occurred in 7 of 10 rabbits at 68 mg/kg, but surviving animals eventually returned to normal a few days 

after exposure was terminated. The authors stated that a dose of 14 mg/kg (65 applications) was a 

NOAEL despite local irritation at the application sites. In view of the exaggerated daily contact with the 

rabbit skin, this value seems reasonable since such high levels of daily exposure would not be the case in 

humans. However, a detailed report of this study was not available for review. 

A study in guinea pigs did not find tributyltin oxide to be a contact sensitizer (Schweinfurth and Gunzel 

1987). 

Ocular Effects. 

Inorganic Tin Compounds. No studies were located regarding ocular effects of inorganic tin in humans 

or animals following dermal exposure. 

Organotin Compounds. Lyle (1958) described the case of a worker who was not wearing protective 

goggles and splashed an unspecified butyltin compound on the face and both eyes were affected. 

Lachrimation and intense suffusion of the conjunctiva appeared within minutes and, despite immediate 

lavage, persisted for 4 days. Tributyltin oxide, tributyltin fluoride and triphenyltin fluoride are extreme 

irritants to rabbits’ eyes (Sheldon 1975). 

3.2.3.3 Immunological and Lymphoreticular Effects 

Inorganic Tin Compounds. No studies were located regarding immunological and lymphoreticular 

effects in humans or animals following dermal exposure to inorganic tin. 

Organotin Compounds. Colosio et al. (1991) reported that a man who spilled a powder pesticide 

formulation containing 19% triphenyltin acetate over exposed skin on his arm developed severe genital 

edema and urticarial eruptions on his trunk. In addition, on day 11 after the accident his serum IgE was 

elevated. Although patch tests conducted with the entire formulation and with each single component of 

the formulation gave negative results, the investigators attributed the findings to poisoning with 

triphenyltin. Tributyltin oxide induced contact sensitization in mice applied the test material for 3 days 

and challenged with it 3 days later (Stringer et al. 1991). The lowest concentration tested, 0.25% by 

volume, triggered a positive response. 
 

TIN AND TIN COMPOUNDS 158 

3. HEALTH EFFECTS 

3.2.3.4 Neurological Effects 

Inorganic Tin Compounds. No studies were located regarding neurological effects in humans or animals 

following dermal exposure to inorganic tin. 

Organic Tin Compounds. The only relevant information is that from the case of a man who spilled a 

powder pesticide formulation containing 19% triphenyltin acetate on his exposed arms, and 10 days after 

the accident, his EEG showed alterations consisting of generalized paroxysmal abnormalities and 

bradyrhythmia (Colosio et al. 1991). Four months after the accident, the EEG showed slight anomalies 

during hyperpnea. 

No studies were located regarding the following effects in humans or animals after dermal exposure to 

inorganic tin or organotin compounds: 

3.2.3.5 Reproductive Effects 

3.2.3.6 Developmental Effects 

3.2.3.7 Cancer 

Inorganic Tin Compounds. No studies were located regarding cancer effects in humans or animals after 

dermal exposure to inorganic tin compounds. 

Organotin Compounds. No studies were located regarding cancer effects in humans after dermal 

exposure to organotin compounds. 

In a limited evaluation of carcinogenicity, tributyltin fluoride was applied to the shaved backs of male 

white mice 3 times/week for a period of 6 months. Treated mice received 15 mg of 5 or 10% of the 

compound in propylene glycol. Hyperplastic skin changes were observed in the 5% group, but not in the 

10% group (Sheldon 1975). Carcinogenic effects were not observed in this study, which was only of 

intermediate duration. No other studies were located regarding cancer effects in animals after dermal 

exposure to organotin compounds. 
 

TIN AND TIN COMPOUNDS 159 

3. HEALTH EFFECTS 

3.2.4 Other Routes of Exposure 

This section provides brief examples of effects of tin compounds that have been studied primarily by 

exposing the animals by a route other than inhalation, oral, or dermal. 

A considerable number of studies have evaluated the developmental effects of both trimethyltin and 

triethyltin following perinatal exposure by intraperitoneal injection of animals, and some studies have 

demonstrated that some alterations persist until adulthood. For example, a single intraperitoneal dose of 

trimethyltin hydroxide (4–6 mg/kg) to rat pups on Pnd 5 reduced growth and impaired performance on 

rope descent when tested on Pnd 20 and 21 (Ruppert et al. 1983). Motor activity in a figure-eight maze 

was increased at 57 days of age and at 120 days of age. The response to acoustic startle was decreased 

during preweaning and as adults. At termination (Pnd 120), whole brain weight and weight of olfactory 

bulbs decreased at 4, 5, and 6 mg/kg, whereas the hippocampus weight was decreased at 5 and 6 mg/kg. 

Similar results were obtained following a single intraperitoneal injection of triethyltin bromide (3 or 

6 mg/kg) also on Pnd 5 (Reiter et al. 1981). Barone et al. (1995) showed that some behavioral alterations 

that can be detected on Pnd 23 after a single injection of triethyltin on Pnd 5, which were no longer 

apparent 3 or 12 months postdosing, became apparent again in 24-month-old rats, suggesting an 

unmasking effects by the natural aging process. 

Chang (1984a, 1984b) did not observe lesions in the hippocampal formation of rats injected 

intraperitoneally with 6 mg/kg trimethyltin chloride between Pnd 1 and 4, but increasing damage to 

Ammon’s horn was seen when dosing occurred between the ages of Pnd 5 and 15. This was followed by 

an apparently reduced sensitivity after Pnd 20. Since the pathological patterns were well-correlated with 

the development and functional maturity of the hippocampal neurons, Chang (1984a, 1984b, 1990) 

postulated that the production of lesions, particularly those in subfield CA3, require functionally mature 

and intact granule cells and their fibers, the mossy fibers. It has also been shown that the day of exposure 

greatly influences the magnitude of cognitive deficits and neuropathology associated with exposure to 

triethyltin (Freeman et al. 1994). 

Trimethyltin and triethyltin have induced ototoxicity in rodents. A single intraperitoneal injection of 4– 

6 mg trimethyltin/kg produced a frequency-dependent loss of auditory sensitivity in rats that was severe 

in the high frequency range (Eastman et al. 1987; Ruppert et al. 1984). Subsequent studies showed that 

the alterations were long-lasting and consisted of a high-frequency hearing loss characterized by elevated 

thresholds in the auditory startle response test detected 11 weeks postdosing (Crofton et al. 1990). 

Thresholds for the brainstem auditory evoked response were also elevated in treated rats 9 weeks 
 

TIN AND TIN COMPOUNDS 160 

3. HEALTH EFFECTS 

postdosing. Microscopic examination of the cochlea from base to apex showed dead outer hair cells 

preferentially in regions associated with high-frequency hearing, in a dose-related manner. A study in 

guinea pigs treated intraperitoneally with a single dose of 2 mg of trimethyltin chloride/kg showed highfrequency impairment, which improved throughout a 6-week period of testing (Fechter and Carlisle 

1990). As seen in the rat, hair cell loss occurred in a portion of the cochlea responsible for encoding highfrequency sound. There also was a marked increase in the diameter of the vessels of the stria vascularis 

(an area containing one of the primary vascular networks in the cochlea) along with signs of atrophy in 

the stria vascularis. However, since the increases in vessel diameter were not confined to the basal 

portion of the cochlea, and were greater in the middle and apical regions than in the base, it seemed that 

the strial pathology was not directly related to hair cell loss or functional impairment. In a different study, 

both trimethyltin and triethyltin were shown to severely disrupt (increase) the compound action potential 

(CAP) threshold in guinea pigs within 30–60 minutes of dosing, but had no significant effect on the 

cochlear microphonic (CM) potential (Clerici et al. 1991). The CAP is generated by the release of 

neurotransmitters from the inner hair cells and the subsequent depolarization of spiral ganglion cells, 

whereas CM reflects electromechanical function of the outer hair cells. In a further study, trimethyltin 

was shown to reduce CAP sensitivity and CM amplitude (Fechter et al. 1992). The effect was relatively 

broad across test frequencies 6 hours after dosing and gradually became restricted to higher frequencies. 

The effect of trimethyltin appears to be a direct effect on the cochlea, as disruption of sound-evoked 

cochlear action potentials can be observed after direct application of trimethyltin to the round window of 

guinea pigs (Liu and Fechter 1995). The results of these and other studies were thought to be consistent 

with the hypothesis that trimethyltin disrupts function at the synapse between the inner hair cell and the 

Type I spiral ganglion cell, possibly by damaging the hair cells or ganglia from uncontrolled production 

of reactive oxygen species (ROS) (Clerici 1996; Fechter and Liu 1994). 

A series of publications from Merkord and coworkers have described the effects of dibutyltin dichloride 

on the pancreas from rats following intravenous injection of the chemical. Earlier studies described an 

acute interstitial pancreatitis in rats developing 24 hours after a single dose followed by a more severe 

pancreatitis with mononuclear cell infiltrates 4–6 days later (Merkord and Hennighausen 1989). In a 

more recent study, the time-course of the pancreatic alterations was followed for up to 28 days with 

interim sacrifices at various intervals after a single dose of 6 mg dibutyltin dichloride/kg (Merkord et al. 

1997). The findings suggested an initial cytotoxic effect on the biliopancreatic duct epithelium leading to 

epithelial necrosis with obstruction of the duct. This was followed by hematogenic effects directly 

injuring pancreatic cells followed by interstitial edema and inflammation. A tendency to a chronic course 

occurred when the obstruction of the duct and cholestasis persisted. Extending the observation period 
TIN AND TIN COMPOUNDS 161 

3. HEALTH EFFECTS 

showed that an active inflammatory process persisted for up to 60 days after dosing (Sparmann et al. 

1997). A study of repeated administration of a slightly lower dose of dibutyltin dichloride (4 mg/kg) at 

intervals of 3 weeks, reported the development of acute pancreatitis and biliopancreatic lesions after 

6 weeks and pancreatic fibrosis and liver lesions after 9–12 weeks (Merkord et al. 2001). In rats followed 

for up to 1 year after a single injection of 6 mg dibutyltin dichloride/kg, the permanent obstruction of 

biliopancreatic secretion and chronic cholestasis led to the formation of deposits inside the dilated duct, 

occasionally with bacterial infiltration and growth. Considerable amounts of tin were detected inside the 

bacterially infected deposits (Jonas et al. 2002). 

3.3 GENOTOXICITY 

In vitro studies with inorganic tin have provided mixed results (Table 3-10). DNA damage was noted in 

Chinese hamster ovary cells incubated with stannous chloride in the absence of metabolic activation, but 

the results for stannic chloride were negative (McLean et al. 1983). Cytogenetic studies also gave 

positive responses with stannous chloride for chromosomal aberrations and sister chromatid exchanges in 

Chinese hamster ovary cells with or without metabolic activation (Gulati et al. 1989). Ganguly et al. 

(1992) incubated peripheral lymphocytes from 27 healthy male volunteers with stannic chloride and 

observed a significant increase in the frequency of chromosomal aberrations. In K562 cells (a cell line 

derived from a chronic myelogenic human leukemia), stannous chloride reduced viability and induced 

DNA damage, as determined by the comet assay (Dantas et al. 2002). The investigators (Dantas et al. 

2002) proposed that genetic damage is produced by ROS generated by the reduction of hydrogen 

peroxide by stannous ions. Earlier research from this group had demonstrated that ROS scavengers and 

metal-ion chelators could prevent, at least partially, the inactivation of Escherichia coli cultures treated 

with stannous chloride (Dantas et al. 1996). Stannous chloride has also been reported to rapidly convert 

hydroperoxy thymidine to mutagenic hydroxymethyl deoxyuridine species in vitro, suggesting a redox 

component in the genotoxic potential of stannous chloride in vivo (Tofigh and Frenkel 1989). 

Table 3-11 presents data on the genotoxicity of organotin compounds in in vitro assays. Hamasaki et al. 

(1993) tested 14 different organotin compounds in two strains of Salmonella typhimurium, TA98 and 

TA100, without metabolic activation. All but dibutyltin dichloride gave negative results in TA98. In 

TA100, the monobutyltins, dibutyltins, and tributyltin compounds gave positive results. Results from 

assays in mammalian cells for a number of trialkyl organotins, with and without metabolic activation, 

showed mostly negative results (Davis et al. 1987; Sasaki et al. 1993). However, other studies have 

reported elevated incidences of chromosomal aberrations, sister chromatid exchanges, and micronuclei in 
TIN AND TIN COMPOUNDS 162 

3. HEALTH EFFECTS 

Table 3-10. Genotoxicity of Inorganic Tin Compounds In Vitro 

Results 

With Without 

Species (test system) End point activation activation Form Reference 

Prokaryotic organisms: 

Bacillus subtilis Rec-assay No data – Stannous chloride Nishioka 1975 

B. subtilis Rec-assay No data – Stannic oxide Nishioka 1975 

Salmonella typhimurium Reverse No data – Stannic chloride Hamasaki et 

TA100, TA98 mutation al. 1993 

Escherichia coli MBL50 DNA damage No data + Stannous chloride Cabral et al. 

1998 

Mammalian cells: 

Chinese hamster ovary DNA damage No data + Stannous chloride McLean et al. 

cells 1983 

Chinese hamster ovary DNA damage No data – Stannic chloride McLean et al. 

cells 1983 

Chinese hamster ovary Sister + + Stannous chloride Gulati et al. 

cells chromatid 1989 

exchanges 

Chinese hamster ovary Chromosomal + + Stannous chloride Gulati et al. 

cells aberrations 1989 

K562 cell line DNA damage No data + Stannous chloride Dantas et al. 

2002 

Human peripheral Chromosomal No data + Stannic chloride Ganguly et al. 

lymphocytes aberrations 1992 

+ = positive result; – = negative result; DNA = deoxyribonucleic acid 
TIN AND TIN COMPOUNDS 163 

3. HEALTH EFFECTS 

Table 3-11. Genotoxicity of Organotin Compounds In Vitro 

Results 

Species (test system) Compound End point 

With 

activation 

Without 

activation Reference 

Prokaryotic organisms: 

Bacillus subtilis TBTO Rec-assay No data – Davis et al. 1987 

Klebsiella 

pneumoniae 

TBTO Fluctuation test No data – Davis et al. 1987 

Salmonella 

typhimurium 

TBTO Plate assay – – Davis et al. 1987 

S. typhimurium TBTO Hepatocyte – No data Davis et al. 1987 

S. typhimurium TBTO Mediated assay – No data Davis et al. 1987 

S. typhimurium TBTO Fluctuation test + – Davis et al. 1987 

S. typhimurium TA98 MBTO Reverse mutation No data – Hamasaki et al. 

1993 

S. typhimurium TA98 MBTC Reverse mutation No data – Hamasaki et al. 

1993 

S. typhimurium TA98 DBTC Reverse mutation No data + Hamasaki et al. 

1993 

S. typhimurium TA98 TBTC Reverse mutation No data – Hamasaki et al. 

1993 

S. typhimurium TA98 TBTO Reverse mutation No data – Hamasaki et al. 

1993 

S. typhimurium TA98 TeBT Reverse mutation No data – Hamasaki et al. 

1993 

S. typhimurium TA98 MPhTC Reverse mutation No data – Hamasaki et al. 

1993 

S. typhimurium TA98 DPhTC Reverse mutation No data – Hamasaki et al. 

1993 

S. typhimurium TA98 TPhTC Reverse mutation No data – Hamasaki et al. 

1993 

S. typhimurium TA98 TePhT Reverse mutation No data – Hamasaki et al. 

1993 

S. typhimurium TA98 MMTC Reverse mutation No data – Hamasaki et al. 

1993 

S. typhimurium TA98 DMTC Reverse mutation No data – Hamasaki et al. 

1993 

S. typhimurium TA98 TMTC Reverse mutation No data – Hamasaki et al. 

1993 

S. typhimurium TA98 TeMT Reverse mutation No data – Hamasaki et al. 

1993 

S. typhimurium 

TA100 

MBTO Reverse mutation No data + Hamasaki et al. 

1993 
 

TIN AND TIN COMPOUNDS 164 

3. HEALTH EFFECTS 

Table 3-11. Genotoxicity of Organotin Compounds In Vitro 

Results 

With Without 

Species (test system) Compound End point activation activation Reference 

S. typhimurium MBTC Reverse mutation No data + Hamasaki et al. 

TA100 1993 

S. typhimurium DBTC Reverse mutation No data + Hamasaki et al. 

TA100 1993 

S. typhimurium TBTC Reverse mutation No data + Hamasaki et al. 

TA100 1993 

S. typhimurium TBTO Reverse mutation No data + Hamasaki et al. 

TA100 1993 

S. typhimurium TeBT Reverse mutation No data – Hamasaki et al. 

TA100 1993 

S. typhimurium MPhTC Reverse mutation No data – Hamasaki et al. 

TA100 1993 

S. typhimurium DPhTC Reverse mutation No data – Hamasaki et al. 

TA100 1993 

S. typhimurium TPhTC Reverse mutation No data – Hamasaki et al. 

TA100 1993 

S. typhimurium TePhT Reverse mutation No data – Hamasaki et al. 

TA100 1993 

S. typhimurium MMTC Reverse mutation No data – Hamasaki et al. 

TA100 1993 

S. typhimurium DMTC Reverse mutation No data + Hamasaki et al. 

TA100 1993 

S. typhimurium TMTC Reverse mutation No data – Hamasaki et al. 

TA100 1993 

S. typhimurium TeMT Reverse mutation No data – Hamasaki et al. 

TA100 1993 

Eukaryotic organisms: 

Saccharomyces TBTO Forward mutation – – Davis et al. 1987 

pombe 

Saccharomyces TBTO Mitotic gene – – Davis et al. 1987 

cerevesiae conversion 

Mammalian cells: 

Chinese hamster TBTO 8-Azaguanine and – – Davis et al. 1987 

cells ovarian resistance 

Chinese hamster TBTO 6-Thioguanine – – Davis et al. 1987 

cells resistance 

Mouse lymphoma TBTO 6-Thioguanine and No data – Davis et al. 1987 

cells Buer resistance 

Chinese hamster TBTO Sister chromatid – – Davis et al. 1987 

cells exchange 
 

TIN AND TIN COMPOUNDS 165 

3. HEALTH EFFECTS 

Table 3-11. Genotoxicity of Organotin Compounds In Vitro 

Results 

Species (test system) Compound End point 

Chinese hamster 

cells 

TBTO Chromosomal 

aberrations 

With 

activation 

+ 

Without 

activation Reference 

– Davis et al. 1987 

Chinese hamster 

cells 

TBTO Inhibition of 

metabolic 

cooperation 

No data – Davis et al. 1987 

Chinese hamster 

cells 

TPhTH Gene mutation – – Oshiro et al. 1991 

Chinese hamster 

cells 

TPhTH Micronucleus + – Oshiro et al. 1991 

Chinese hamster 

cells 

TPhTH Micronucleus + + Chao et al. 1999 

Chinese hamster 

cells 

TPhTA Micronucleus + – Chao et al. 1999 

Chinese hamster 

cells 

Chinese hamster 

cells 

Chinese hamster 

cells 

TPhTA 

TPhTH 

TPhTC 

Sister chromatid 

exchange 

Sister chromatid 

exchange 

Chromosomal 

aberrations 

+ 

+ 

No data 

– 

– 

– 

Chao et al. 1999 

Chao et al. 1999 

Sasaki et al. 1993 

Chinese hamster 

cells 

TPhTA Chromosomal 

aberrations 

No data – Sasaki et al. 1993 

Chinese hamster 

cells 

TPhTH Chromosomal 

aberrations 

No data – Sasaki et al. 1993 

Chinese hamster 

cells 

TBTC Chromosomal 

aberrations 

No data – Sasaki et al. 1993 

Chinese hamster 

cells 

DBTC Spindle inhibition No data + Jensen et al. 1991b 

Chinese hamster 

cells 

TBTF Chromosomal 

aberrations 

No data – Sasaki et al. 1993 

Chinese hamster 

cells 

TBTO Chromosomal 

aberrations 

No data – Sasaki et al. 1993 

Chinese hamster 

cells 

TMTC Spindle inhibition No data + Jensen et al. 1991b 

Chinese hamster 

cells 

TBTC Spindle inhibition No data + Jensen et al. 1991b 

Chinese hamster 

cells 

DMTC Spindle inhibition No data + Jensen et al. 1991b 

Chinese hamster 

cells 

TPhTC Spindle inhibition No data + Jensen et al. 1991b 

Chinese hamster 

cells 

DPhTC Spindle inhibition No data + Jensen et al. 1991b 
 

TIN AND TIN COMPOUNDS 166 

3. HEALTH EFFECTS 

Table 3-11. Genotoxicity of Organotin Compounds In Vitro 

Results 

With Without 

Species (test system) Compound End point activation activation Reference 

Human peripheral TMTC Chromosomal No data + Ghosh et al. 1991 

lymphocytes aberrations 

Human peripheral TMTC Sister chromatid No data + Ganguly et al. 1992 

lymphocytes exchange 

Human peripheral TMTC Micronucleus No data + Ghosh et al. 1990 

lymphocytes 

+ = positive result; – = negative result; DBTC = di-n-butyltin dichloride; DMTC = dimethyltin dichloride; 

DPhTC = diphenyltin dichloride; MBTC = n-butyltin trichloride; MBTO = mono-n-butyltin oxide; MMTC = methyltin 

trichoride; MPhTC = phenyltin trichloride; TBTC = tri-n-butyltin chloride; TBTF = tributyltin fluoride; 

TBTO = bis(tributyltin)oxide; TeBT =tetra-n-butyltin; TeMT = tetramethyltin; TePHT = tetraphenyltin; 

TMTC = trimethyltin chloride; TPhTA = triphenyltin acetate; TPhTC = triphenyltin chloride; TPhTH = triphenyltin 

hydroxide 
TIN AND TIN COMPOUNDS 167 

3. HEALTH EFFECTS 

peripheral lymphocytes obtained from healthy individuals and incubated with trimethyltin chloride 

(Ganguly et al. 1992; Ghosh et al. 1990, 1991). Triphenyltin compounds were positive in tests for 

induction of micronuclei and sister chromatid exchanges in Chinese hamster cells (Chao et al. 1999; 

Oshiro et al. 1991). 

A limited number of studies have examined the in vivo genotoxic effects of organotins administered in 

animals (Table 3-12). In vivo micronucleus tests for tributyltin oxide in mice have produced mixed 

results. Neither tributyltin oxide nor triphenyltin chloride injected in doses up to 100 mg/kg in mice 

increased the incidence of micronuclei in blood reticulocytes (Yamada and Sasaki 1993). Similar results 

were reported by Schweinfurth and Gunzel (1987) after administration of a single dose of 125 mg/kg of 

tributyltin oxide to mice. In contrast, Davis et al. (1987) reported an increase in micronuclei in mice 

treated with a single dose of 60 mg/kg tributyltin oxide. According to Schweinfurth and Gunzel (1987), 

the difference between their results and those of Davis et al. (1987) may be due to a higher number of 

polychromatic erythrocytes per animal that were scored in Schweinfurth and Gunzel (1987). Sagelsdorff 

et al. (1990) treated male and female rats with a single gavage dose (approximately 3.5 mg/kg) of 

14C-dioctyltin dichloride and isolated DNA from thymus and liver 96 hours later to determine possible 

adduct formation. They detected radioactivity incorporated to all DNA fractions via biosynthesis, but 

there was no adduct formation. Gavage administration of three doses of 2 mg/kg of triphenyltin acetate to 

mice or a single dose of 12.5 mg/kg significantly increased the incidence of micronucleated reticulocytes; 

a similar significant increase occurred following a single dose of 2.5 mg/kg of triphenyltin hydroxide 

(Chao et al. 1999). Intraperitoneal treatment of mice with 0.25–1 mg/kg of trimethyltin significantly 

increased the incidence of chromosomal aberrations in mouse bone marrow cells 6–24 hours after dosing 

(Ganguly 1994). 

3.4 TOXICOKINETICS 

3.4.1 Absorption 

The results of toxicity studies suggest that inorganic tin compounds are not readily absorbed after oral or 

inhalation exposure and show only limited effects after dermal exposure. Organotin compounds are more 

readily absorbed than inorganic tin compounds by these three routes of exposure. 
TIN AND TIN COMPOUNDS 168 

3. HEALTH EFFECTS 

Table 3-12. Genotoxicity of Organotin Compounds In Vivo 

Species 

(test system) Compound End point Results Reference 

Insect system: 

Drosophilia TBTO Test for sex-linked recessive – Davis et al. 1987 

melanogaster lethal mutations 

Mammalian system: 

Mice TBTO Micronucleus test; single dose + Davis et al. 1987 

60 mg/kg body weight 

Mice TBTO Micronucleus test; cytotoxic – Schweinfurth and Gunzel 

doses; highest 125 mg/kg body 1987 

weight 

Mice TPhTA Micronucleus; single 12.5 mg/kg + Chao et al. 1999 

oral dose 

TPhTH Micronucleus test; single + Chao et al. 1999 

2.5 mg/kg oral dose 

Rat DOTC Liver and thymus DNA adduct – Sagelsdorff et al. 1990 

single oral gavage ~3.5 mg/kg 

Mice TMTC Chromosomal aberrations; + Ganguly 1994 

three intraperitoneal doses 0.25– 

1 mg/kg 

Mice	 TBTO Micronucleus; single oral dose – Yamada and Sasaki 1993 

TPhTC 100 mg/kg 

+ = positive result; – = negative result; DNA = deoxyribonucleic acid; DOTC = dioctyltin dichloride; 

TBTO = bis(tributyltin)oxide; TMTC = trimethyltin chloride; TPhTA = triphenyltin acetate; TPhTC = triphenyltin 

chloride; TPhTH = triphenyltin hydroxide 
TIN AND TIN COMPOUNDS 169 

3. HEALTH EFFECTS 

3.4.1.1 Inhalation Exposure 

No quantitative studies were located regarding absorption in humans or animals after inhalation exposure 

to inorganic tin or organotin compounds. However, limited data summarized in Section 3.2.1 suggest that 

absorption of organotins by the inhalation route is possible, as occurred for example in cases for subjects 

who exhibited serious neurological effects after accidental exposure to vapors of a trimethyltin (Feldman 

et al. 1993; Fortemps et al. 1978; Rey et al. 1984; Ross et al. 1981; Saary and House 2002; Yanofsky et 

al. 1991). Dermal exposure may have also occurred in these cases. 

3.4.1.2 Oral Exposure 

Inorganic Tin Compounds. Johnson and Greger (1982) conducted a balance study in eight healthy adult 

males, who were placed on diets containing either 0.1 mg Sn/day (basal diet) or 50 mg Sn/day 

(supplemented with stannous chloride). Subjects were placed on the diets for 20 days and intakes and 

excretion were measured daily in two 6-day periods (following a 6-day adjustment to the diets). Average 

fecal excretion was 55% of the daily intake in the basal group and 97% in the supplemented group, 

suggesting net absorption of 45 and 3%, respectively. Average urinary excretion was 26% of the daily 

intake in the basal group and 2.4% in the supplemented group. Estimates of absorption in individuals 

ranged from -4 to 71% of the daily intake in the basal group and from -7 to 9% in the supplemented 

group. These observations suggest that gastrointestinal absorption of tin, in humans, decreases with 

increasing dose. An alternative explanation for the differences in absorption of tin in the basal and 

supplemented diets is that tin naturally incorporated into food may be more readily absorbed than tin 

added as stannous chloride to food. Consistent with the former explanation are observations from 

Calloway and McMullen (1966). In this study, nine healthy adults were placed on diets for 24 days 

consisting of either fresh food (10 mg Sn/day), canned food that had been stored for 20 months at 1 qC 

(26 mg Sn/day), or canned foods that had been stored for 20 months at 37 qC (163 mg Sn/day). Tin was 

not detected in the urine in this study, and the amount excreted in the feces was the same as the amount 

ingested. Thus, net absorption of tin could not be detected at these higher levels of intake, in contrast to 

the observations made at lower intakes (0.1 mg Sn/day; Johnson and Greger 1982). 

Studies conducted in animals suggest that fractional absorption of ingested inorganic Sn[II] is higher, by a 

factor of approximately 4, than Sn[IV]; however, the associated anion appears to have little or no effect 

on the absorption fraction. Gastrointestinal absorption was 2.85 and 0.64% of the administered dose, in 
 

TIN AND TIN COMPOUNDS 170 

3. HEALTH EFFECTS 

rats, after a single oral dose of 113Sn[II]citrate or 113Sn[IV]citrate (20 mg Sn/kg), respectively (Hiles 

1974). Fractional absorption of tin after single oral doses (20 mg Sn/kg) of stannous pyrophosphate 

(

113Sn[II]2P2O7), stannous fluoride (113Sn[II]F2), or stannic fluoride (113Sn[IV]F4) appeared to be similar to 

that of 113Sn[II]citrate and 113Sn[IV]citrate (i.e., <5%), based on comparisons of tissue and excreta levels 

(Hiles 1974). Furchner and Drake (1976) concluded, from comparisons of tissue retention kinetics after 

oral gavage and intravenous injection of stannous chloride (113SnCl2), that gastrointestinal absorption of 

Sn[II] was similar (less than 5%) in dogs, mice, rats, and monkeys. 

Organotin Compounds. No quantitative estimates of absorption of organotin compounds in humans 

were located. The detection of butyltin compounds in blood and in postmortem human liver samples 

indicates that butyltin compounds are absorbed in humans (Kannan et al. 1999; Nielsen and Strand 2002). 

Also, numerous deaths occurred in a poisoning episode with presumably accidental ingestion of 

triethyltin in France in 1954 (WHO 1980) indicating that absorption occurred. In addition, Kreyberg et 

al. (1992) described the case of a woman who ingested an unknown amount of trimethyltin and died 

6 days after consuming the chemical. 

Methyltin Compounds. Quantitative estimates of absorption of methyltin compounds after ingestion 

were not located. Tin levels in brain, kidney, and liver were similar in neonatal rats that received oral 

doses of 1 mg/kg trimethyltin hydroxide (0.66 mg Sn/kg) or triethyltin sulfate (0.44 mg Sn/kg), 

suggesting that both compounds may be absorbed similarly (Mushak et al. 1982). 

Ethyltin Compounds. Rats administered a single oral dose of approximately 25 mg/kg ethyltin 

trichloride (12 mg Sn/kg) excreted 92% (range 89–95%) of the dose in feces and 1.2% (range 1–2%) in 

urine, suggesting that at least 8% of the dose had been absorbed (Bridges et al. 1967). This is a minimum 

estimate of absorption, since absorbed ethyltin compounds are secreted in bile and excreted in feces (see 

Section 3.4.4.4). 

Butyltin Compounds. Mice administered a single oral dose of approximately 180 μmol/kg, respectively, 

of mono-, di-, or tributyltin (23 mg Sn/kg) excreted, approximately 2, 20, or 35% of the dose in urine 

within 96 hours following dosing (Ueno et al. 1994). These values are minimum estimates of the 

absorption of the ingested dose because they do not account for absorbed tin excreted by other routes 

(e.g., bile-fecal pathway; see Section 3.4.4.4). However, these results indicate that the fraction of an 

ingested dose of butyltin compounds excreted in urine increases with increasing number of butyl 
 

TIN AND TIN COMPOUNDS 171 

3. HEALTH EFFECTS 

moieties, suggesting that more-highly butylated tin compounds may be absorbed to a greater extent 

(Kimmel et al. 1977). 

Phenyltin Compounds. Quantitative estimates of absorption of phenyltin compounds after ingestion 

were not located. Urinary excretion of tin compounds (as total tin) over a 96-hour period following a 

single oral dose of tri-, di-, or monophenyltin (15.5 mg Sn/kg) was <1% of the administered dose of tin 

(Ohhira and Matsui 1993a). This is a minimum estimate of the absorbed fraction as it does not account 

for excretion by other routes or retention of tin. 

3.4.1.3 Dermal Exposure 

Inorganic Tin Compounds. No studies were located regarding absorption in humans or animals after 

dermal exposure to inorganic tin compounds. 

Organotin Compounds. No studies were located regarding absorption in humans after dermal exposure 

to organotin compounds. 

Quantitative estimates of dermal absorption of organotin compounds in animals were not located. 

Organotin compounds, including trimethyltin, triethyltin, tributyltin, and triphenyltin, have produced 

systemic toxicity in animals after dermal exposure, indicating that dermal exposures can result in 

systemic absorption of tin (Mori et al. 1984; Stoner 1966). 

3.4.2 Distribution 

The human body has been estimated to contain less than 17 mg of tin, with approximately 6 mg in soft 

tissues and the remaining fraction associated with skeletal tissues (ICRP 1981a). In a survey of tin 

concentrations in postmortem human tissues collected from several hundred subjects, the highest 

concentrations occurred in the kidney, liver, lung, and bone (Kehoe et al. 1940; Schroeder et al. 1964; see 

Table 3-13). Tin was not detected in brain tissue (Kehoe et al. 1940). In kidney and liver, the highest 

concentrations (kidney 57–60 mg/kg, liver 48–61 mg/kg) were observed at ages 1–10 years; 

concentrations were 20–40 mg/kg thereafter; tin was not detected in kidney or liver at birth (Schroeder et 

al. 1964). In the lungs, tin appeared to increase with age, with the highest levels (53–64 mg tin/kg) at 

ages 51–84 (Schroeder et al. 1964). Although, these data indicate trends in tin accumulation in human 

tissues, wide variations in tissue concentrations were observed, most likely reflecting variation in 
TIN AND TIN COMPOUNDS 172 

3. HEALTH EFFECTS 

Table 3-13. Mean Tin Levels in Human Tissuesa 

Tissue Wet weight (mg/kg) 

Kidney 0.2–0.78 

Heart 0.2 

Brain ND 

Liver 0.35–1.0 

Spleen 0.2 

Lung 0.45–1.20 

Muscle 0.1 

Bone 0.5–8.0 

Gastrointestinal tract 0.1–0.5 

ND = Not detected 

a

Adapted from Kehoe et al. 1940; Schroeder et al. 1964 
TIN AND TIN COMPOUNDS 173 

3. HEALTH EFFECTS 

exposures and, possibly the health/exposure history of the tissue donors (Tipton and Cook 1963; Tipton et 

al. 1963). Additional information regarding tin and organotin levels in human tissues and fluids is 

presented in Table 6-5. 

When fresh human whole blood was incubated with triethyl[113Sn]tin chloride, the red blood cell:plasma 

tin ratio was 1.9 (Rose and Aldridge 1968). This ratio was substantially different from the ratio observed 

in rat blood (19), and similar to that in other rodent species (range, 1–5). Interspecies differences have 

been attributed to variable binding of tin (or triethyltin) to hemoglobin (Rose 1969) and may also be 

applicable to trimethyltin, which also shows a pronounced accumulation in rat red blood cells (Brown et 

al. 1984; see Section 3.4.2.2 for further discussion). 

3.4.2.1 Inhalation Exposure 

No studies were located regarding distribution in humans or animals after inhalation exposure to 

inorganic tin or organotin compounds. 

3.4.2.2 Oral Exposure 

Inorganic Tin Compounds. No studies were located regarding distribution in humans after oral exposure 

to inorganic tin compounds; however, data are available on tissue levels of tin in general populations 

(Schroeder et al. 1964; see Section 3.4.2). 

Consistent with observations made of the tissue distribution of tin in humans, bone, kidney, and liver are 

major sites of deposition of tin in rats and mice, after oral administration of inorganic tin compounds 

(Hiles 1974; NTP 1982; Schroeder et al. 1968; Yamaguchi et al. 1980). Levels of tin in bone, kidney, and 

liver were 0.02–1% of the administered dose of 113Sn in rats that received a single oral dose of 20 mg 

Sn/kg/day as stannous pyrophosphate (113Sn[II]2P2O7), stannous fluoride (113Sn[II]F2), stannic fluoride 

(

113Sn[IV]F4), 113Sn[II]citrate, or 113Sn[IV]citrate (Hiles 1974). Levels in blood were 0.01% (or less) of 

the administered dose. In rats that received 20 mg Sn/kg/day of stannous fluoride (113Sn[II]F2) or stannic 

fluoride (113Sn[IV]F4), for a period of 28 days, levels of tin in kidneys and liver were approximately the 

same as after a single oral dose (Hiles 1974); however, levels in bone were higher after multiple dosing, 

suggesting slower elimination kinetics of tin from bone, relative to kidney and liver (see Section 3.4.4.4). 
 

TIN AND TIN COMPOUNDS 174 

3. HEALTH EFFECTS 

Accumulation of tin in bone has also been observed in rats and mice exposed to stannous chloride 

(Sn[II]Cl2) (NTP 1982; Yamaguchi et al. 1980). Tissue concentration ratios were approximately 43 for 

bone:kidney and 32 for bone:liver after 90 days of oral (gavage) doses of stannous chloride; the 

bone:tissue ratios increased with increasing doses of 0.3, 1, or 3 mg/kg/day (Yamaguchi et al. 1980). 

Chronic exposures of rats, at much higher doses (60–70 mg/kg/day, 1,000 ppm in diet), resulted in tissue 

concentration ratios of approximately 0.5 for bone:kidney and 55 for bone:liver; increasing the dose by a 

factor of approximately 2, resulted in a proportional increase bone:kidney and bone:liver ratios (NTP 

1982). Chronic exposures of mice (230–280 mg/kg/day, 1,000 ppm in diet), resulted in tissue 

concentration ratios of approximately 30 for bone:kidney and 60 for bone:liver (NTP 1982). Bone:kidney 

and bone:liver ratios, in rats and mice, were similar in female and males (NTP 1982). These studies 

indicate a dose-dependence and possible species differences (i.e., mice compared to rats) in the tissue 

distribution of tin after exposures to stannous chloride. However, it should be noted that the dosages 

administered in the NTP (1982) study resulted in gastrointestinal tract toxicity, which may have affected 

absorption of administered tin. 

Schroeder et al. (1968) chronically exposed rats to 5 ppm stannous chloride in drinking water and found 

relatively high concentrations of tin in spleen. Tissue concentration ratios (spleen:tissue) were: 

kidney, 11; liver, 5; heart, 2; and lung, 3. Tin concentrations in brain were approximately twice that of 

blood in rats exposed to stannous chloride (Sn[II]Cl2, 100, 250, or 500 mg/L, 63, 156, or 313 mg Sn/L) 

for up to 18 weeks, and appeared to increase with increasing duration of exposure, suggesting the 

possibility of accumulation of tin in brain with prolonged exposure to stannous chloride (Savolainen and 

Valkomen 1986). 

Animal studies in which absorbed tin was measured in tissues following parenteral injection of 

Sn[II]chloride (113SnCl2), confirmed the above observations; i.e., that bone, kidney, and liver are major 

sites of deposition of absorbed Sn[II] (see Section 3.4.4.4). 

Tin was not detected in the uterine horns or combined fetuses and placentas in rats following daily 

ingestion of 20 mg Sn/kg/day as 113SnF2, or 113SnF4 beginning on the day of conception (Hiles 1974). 

However, on Gd 21, fetuses of dams administered 20 mg Sn/kg/day as SnF2 (approximately 100 mg Sn 

cumulative dose) contained approximately 0.2 μg Sn/g, or approximately 0.2% of the cumulative 

administered dose (detection limit, 0.1 μg/g). This suggests the possibility that, in the rat, tin 

administered orally as stannous chloride may be transferred to the fetus. 
 

 

TIN AND TIN COMPOUNDS 175 

3. HEALTH EFFECTS 

No studies on transfer of tin to breast milk following oral exposure (or exposure by other routes) to 

inorganic tin compounds were located. 

Organotin Compounds. No studies were located regarding distribution in humans after oral exposure to 

organotin compounds. 

Methyltin Compounds. Studies conducted in animals indicate that ingested methyltin compounds 

distribute to soft tissues, with the highest levels usually observed in liver. Species differences in the 

tissue distribution of trimethyltin have been observed. In marmosets, 1–13 days following a single oral 

dose of 3–4.5 mg/kg trimethyltin chloride (1.8–2.4 mg Sn/kg), brain:blood concentration ratios ranged 

from 6 to 10; whereas, in rats, 5 days following an oral dose of 10 mg/kg (6 mg Sn/kg), blood:brain ratios 

were approximately 38 (Brown et al. 1979, 1984). Mushak et al. (1982) also observed relatively high 

blood:tissue ratios of tin in neonatal rats that received oral doses of trimethyltin hydroxide (0.66 mg 

Sn/kg/day, Pnds 2–29): brain, 42; kidney, 22; and liver, 8. Following multiple oral doses of 4 mg/kg 

(2.4 mg Sn/kg) for 7 days, blood:brain ratios in the rat ranged from 30 to 48 (Brown et al. 1979). The 

relatively high blood levels of tin in rats, compared to other species, have been attributed to a more 

pronounced accumulation of trimethyltin in red blood cells. When samples of blood from rats were 

incubated with trimethyltin, the blood:plasma concentration ratio was approximately 67, compared to 

approximately 1 in the marmoset, gerbil, and hamster (Brown et al. 1984). The mechanism for the 

difference has not been elucidated. 

Ethyltin Compounds. In animals, ingested ethyltin, along with five dealkylation products, distribute to 

soft tissues, including brain, kidney and liver. In rats, following 5 oral doses of 10 mg/kg/day triethyltin 

(5.8 mg Sn/kg/day), tissue:blood concentration ratios of triethyltin were approximately: brain, 8; kidney, 

4; and liver, 0.5 (Iwai et al. 1982b). Following the same dose of tetraethyltin (5.1 mg Sn/kg/day), both 

tetra- and triethyltin were detected in tissues, reflecting dealkylation of tetraethyltin (see Section 3.4.3). 

The brain:blood ratio of tetraethyltin was <1 whereas the brain:blood ratio of triethyltin was >8. In 

neonatal rats that received oral doses of triethyltin sulfate (0.44 mg Sn/kg/day, Pnds 2–29), tissue:blood 

tin concentration ratios were: 0.7, brain; kidney, 0.8; liver, 3. 4 (Mushak et al. 1982). The higher 

liver:blood ratio of total tin, compared to that of triethyltin, following ingestion of triethyltin, also may 

reflect the dealkylation of trimethyltin in the liver (see Section 3.4.3). 

Butyltin Compounds. Similar to ethyltin compounds, ingested butyltin compounds and their dealkylation 

products distribute to soft tissues, including brain, kidney, and liver. In rats, following five oral doses of 
TIN AND TIN COMPOUNDS 176 

3. HEALTH EFFECTS 

10 mg/kg tributyltin (5.8 mg Sn/kg), tissue:blood concentration ratios of tributyltin were approximately: 

brain, <1; kidney, 2–4; and liver 1–2 (Iwai et al. 1982b). Following the same dose of tetrabutyltin, 

tissue:blood concentration ratios of tetrabutyltin were approximately: brain, <1; kidney, 10–12; and 

liver, 20. In rats given a single oral dose of 40 mg/kg tributyltin fluoride (15 mg Sn/kg), transient 

elevations in tributyltin, dibutyltin, monobutyltin, and inorganic tin were observed in brain and liver over 

the 8-day period following the dose, indicating that dealkylation had occurred (Iwai et al. 1981, see 

Section 3.4.3). In neonatal rats that received oral doses of tributyltin acetate (1.0 mg Sn/kg/day, Pnds 2– 

29), tissue:blood tin concentration ratios(possibly limited by the detection limit for blood tin) were: 

brain, 2.6; kidney, 19; and liver, 24 (Mushak et al. 1982). 

In rats exposed to tributyltin oxide in the diet (0.25, 1, 4, or 16 mg/kg/day; 0.1, 0.4, 1.6, or 6.4 mg 

Sn/kg/day) for 4 weeks, total tin in kidney, liver, and brain increased with increasing dosage, and were 

similar in females and males (Krajnc et al. 1984). Levels in the brain and adipose tissue were 10–20% of 

the kidney and liver levels. 

Twenty-four hours after administration of a single dose of 22 mg dibutyltin diacetate/kg to pregnant rats 

on Gd 8, dibutyltin and monobutyltin were detected in maternal blood and liver, and in the embryos, 

indicating placental transfer (Noda et al. 1994). In the embryos, the concentration of dibutyltin was 6– 

7 times higher than that of monobutyltin. Nakamura et al. (1993) had also detected dibutyltin in fetuses 

on Gd 18 after administration of the chemical to the pregnant rats on Gd 7–17. 

Phenyltin Compounds. Studies conducted in animals indicate that ingested phenyltin compounds and 

dearylated metabolites (see Section 3.4.3) distribute to soft tissues, including brain, kidney, liver, and 

pancreas. In hamsters and rats, following a single oral dose of 50 mg triphenyltin chloride (15 mg Sn/kg), 

triphenyltin and dearylated metabolites, including inorganic tin, were detected in brain, blood, kidney, 

liver and pancreas (Ohhira and Matsui 1996). The highest concentrations of triphenyltin and metabolites 

were found in liver and kidney. In rats, tissue:blood ratios for triphenyltin, 48 hours after the dose, were 

approximately: brain, 10; kidney, 21; liver, 17; and pancreas, 4. Similar ratios were observed in hamsters: 

brain, 9; kidney, 11; liver, 21; and pancreas, 11. In neonatal rats that received oral doses of triphenyltin 

acetate (0.87 mg Sn/kg/day, Pnds 2–29), tissue:blood tin concentration ratios (based on the detection limit 

for blood) were: brain, 3; kidney, 6; and liver, 14 (Mushak et al. 1982). 
TIN AND TIN COMPOUNDS 177 

3. HEALTH EFFECTS 

In rats, following a single oral dose of 55.4 mg/kg tetraphenyltin (15 mg Sn/kg), tetraphenyltin, and the 

dearylated metabolites (tri-, di-, and monophenyltin) were detected in kidney and liver (Ohhira and 

Matsui 2003). 

3.4.2.3 Dermal Exposure 

No studies were located regarding distribution in humans or animals after dermal exposure to inorganic 

tin or organotin compounds. 

3.4.2.4 Other Routes of Exposure 

Inorganic Tin Compounds. Animal studies, in which absorbed tin was measured in tissues following 

parenteral injection of Sn[II]chloride (113SnCl2), confirm observations from oral exposure studies 

(Section 3.4.2.3) that bone, kidney, and liver are major sites of deposition of absorbed Sn[II] (Furchner 

and Drake 1976; Hiles 1974). In rats that received an intraperitoneal injection of stannous chloride 

(

113Sn[II]Cl2, 0.006 μg/kg), tissue levels (percent of body burden) 1 day after dosing were: bone, 50%, 

kidney, 3.5%; liver, 6%; and skeletal muscle, 20%; thus, muscle also appears to a major site of deposition 

of Sn[II] (Furchner and Drake 1976). 

Organotin Compounds. Animal studies, in which organotin compounds were administered parenterally 

confirm observations made following oral exposures; organotin compounds distribute to soft tissues, 

including brain, kidney, and liver. 

Methyltin Compounds. In rats administered a single intraperitoneal dose of 6 mg/kg trimethyltin (4.3 mg 

Sn/kg), tin distributed to brain, heart, kidney, and liver, with levels in brain (ng/g protein) that were 15– 

50% of that in other tissues (Cook et al. 1984a). Tin distribution was uniform across the brain regions, 

cerebellum, medulla-pons, hypothalamus, hippocampus, and striatum (Cook et al. 1984a). Tin in brain, 

kidney, and liver were lower after a dose of 6 mg/kg trimethyltin (4.3 mg Sn/kg) than after a dose of 

6 mg/kg triethyltin (2.5 mg Sn/kg). 

Ethyltin Compounds. In rats, 5 days following a single intravenous dose of 10 mg/kg triethyl[113Sn]tin 

chloride (5 mg Sn/kg), tissue:blood tin ratios were: liver, 1.3; kidney, 0.6; brain, 0.2; skeletal muscle, 

0.15; and spinal cord, 0.1; levels were similar in brain stem cerebellum, cerebrum, and cortex (Rose and 

Aldridge 1968). These observations are consistent with those of Cook et al. (1984a): following a single 
 

 

TIN AND TIN COMPOUNDS 178 

3. HEALTH EFFECTS 

intraperitoneal dose of 6 mg/kg triethyltin (3.5 mg Sn/kg), similar levels of tin were observed in heart, 

kidney, and liver, and levels in brain were 15–25% of that of kidney and liver. Increasing the intravenous 

dose of triethyltin from approximately 0.6 to 5 mg/kg (0.3–2.5 mg Sn/kg) in rats resulted in proportional 

increases in levels of tin in blood, brain, kidney, and liver, with no evidence of a limitation in capacity for 

deposition in these tissues (Rose and Aldridge 1968). 

Species differences in deposition of tin in red blood cells have been observed following parenterallyadministered triethyltin to animals (Rose and Aldridge 1968). In rats, 4–5 hours following a single 

intravenous dose of 10 mg/kg triethyl[113Sn]tin chloride (5 mg Sn/kg), substantially higher levels of tin in 

blood (relative to other tissues) were observed, compared to the hamster and guinea pig, although the 

distribution to other tissues was similar among rodent species. When samples of whole blood from rats 

were incubated with triethyl[113Sn]tin chloride, the red blood cell:plasma tin concentration ratio was 19; 

ratios observed in blood from other rodent species were considerably lower (1–5) and, in human blood, 

the ratio was 1.9, suggesting that the mechanism for the species differences in red blood cell:plasma ratios 

involved uptake and/or retention of triethyltin (or tin derived from triethyltin) in red blood cells (Rose and 

Aldridge 1968). Rat hemoglobin bound more 113Sn when incubated with triethyl[113Sn]tin than 

hemoglobins isolated from other rodents, or from humans (Rose and Aldridge 1968). 

3.4.3 Metabolism 

Inorganic Tin Compounds. No studies were located in humans or animals on metabolism of inorganic 

tin after inhalation, oral, or dermal exposure. 

Organotin Compounds. No studies were located in humans on metabolism after inhalation, oral, or 

dermal exposure to organotin compounds. Microsomes prepared from human liver dealkylate tributyltin 

to form di- and monobutyltin metabolites, suggesting that similar pathways may be active in humans, in 

vivo (Ohhira et al. 2003). This would be consistent with the detection of dibutyltin and monobutyltin in 

postmortem human liver samples (Nielsen and Strand 2002) and with the more substantial evidence for 

dealkylation of alkyltins, including butyltins, in various nonhuman species (see below). 

Ethyltin Compounds. Studies conducted in rats indicate that tetra-, tri- and diethyltin undergo 

dealkylation to ethyltin compounds (Bridges et al. 1967; Cremer 1958). Dealkylation and hydroxylation 

of the ethyl moieties are catalyzed by microsomal monooxygenase(s) of liver, and possibly other tissues 

(Kimmel et al. 1977). 
 

TIN AND TIN COMPOUNDS 179 

3. HEALTH EFFECTS 

Butyltin Compounds. Studies conducted in rats indicate that tributyltin undergoes dealkylation to di- and 

monobutyltin compounds (Iwai et al. 1981, 1982; Matsuda et al. 1993; Ueno et al. 1994). The butyl 

moieties are also oxidized at carbon 3 to yield 3-hydroxybutyl and 3-oxobutyl metabolites; and at carbon 

4, to yield the 4-hydroxybutyl and 3-carboxy metabolites (Matsuda et al. 1993). The simple dealkylation 

products were the principal metabolites detected in blood and brain following a 2 mg/kg oral dose of 

tributyltin chloride, whereas in kidney and liver, hydroxy-, carboxy-, and oxo-metabolites were the 

dominant metabolites (Matsuda et al. 1993). Dealkylation and hydroxylation are catalyzed by 

microsomal monooxygenase(s) (Kimmel et al. 1977; Ohhira et al. 2003). The alkyl products of 

dealkylation are conjugated with glutathione and further metabolized to mercapturic acid derivatives 

(Suzuki et al. 1999b). 

Phenyltin Compounds. Studies conducted in hamsters and rats indicate that tetra-, tri-, di-, and 

monophenyltin compounds are dearylated. The dearylated metabolites, including inorganic tin, can be 

found in kidney and liver after an oral exposure to phenyltin compounds (Ohhira and Matsui 1993a, 

1993b, 2003; Ohirra et al. 1996). Dearylation of phenyltin compounds is catalyzed by microsomal 

monooxygenase(s) in liver, and possibly in other tissues (Ohhira et al. 2003). A recent study of CYP 

isoforms in rat hepatocytes showed that CYP2B1 had a small metabolic capacity for triphenyltin, but the 

principal CYP for triphenyltin metabolism in rats was CYP2C6 (Ohhira et al. 2004). Support for this 

finding was provided by experiments in which anti-rat CYP2C6 antibodies and cimetidine, a selective 

CYP2C6 inhibitor, inhibited triphenyltin dearylation activity in the hepatic microsomes of rats (Ohhira et 

al. 2004). 

3.4.4 Elimination and Excretion 

3.4.4.1 Inhalation Exposure 

Inorganic Tin Compounds. No studies were located regarding excretion in humans or animals after 

inhalation exposure to inorganic tin. 

Organotin Compounds. No studies were located regarding excretion in humans or animals after 

inhalation exposure to inorganic tin, although tin was detected in the urine from a fatal inhalation case 

described by Rey et al. (1984). 
 

TIN AND TIN COMPOUNDS 180 

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3.4.4.2 Oral Exposure 

Inorganic Tin Compounds. Feces and urine are major routes of excretion of ingested tin in humans 

(Calloway and McMullen 1966; Johnson and Greger 1982, see Section 3.1.4.2). In eight healthy adult 

males who were placed on diets (for 20 days) containing 0.1 mg Sn/day (basal diet) or 50 mg Sn/day 

(supplemented with stannous chloride), average fecal excretion was 55% of the daily intake in the basal 

group and 97% in the supplemented group (Johnson and Greger 1982). Average urinary excretion was 

26% of the daily intake in the basal group and 2.4% in the supplemented group, suggesting that urine was 

a major route of excretion of absorbed tin. These and other observations (Calloway and Mullen 1966) 

also suggest that gastrointestinal absorption of tin in humans may decrease with increasing dose, possibly 

reflecting a tight homeostatic control of tin absorption (see Section 3.4.1.2). 

In dogs, mice, rats, and Rhesus monkeys, tin ingested as Sn[II] or Sn[IV] compounds is excreted 

primarily in feces; however, urine and bile appear to be major routes of excretion of absorbed Sn[II] (see 

Section 3.4.4.4). In rats, 48 hours after dosing (20 mg Sn/kg/day), 95% of the administered 113Sn (as Sn 

[II], Sn [IV] citrate, Sn[II]2P2O7, Sn[II]F2, or Sn[IV]F4) was recovered in feces, while <1% was detected 

in urine (Hiles 1974). Similar results were obtained in dogs, mice, rats, and Rhesus monkeys (Furchner 

and Drake 1976). 

Whole body and tissue retention kinetics have been measured in mice, monkeys, rats, and dogs after an 

oral gavage dose of stannous chloride (Sn[II]Cl2) (Furchner and Drake 1976). Whole-body elimination 

kinetics of absorbed Sn[II] were similar in all four species and could be described with 1- or 

2-compartment models in which 96–100% of the initial body burden is eliminated with a half-time of 

0.2–0.4 days. In Rhesus monkeys (dose, 0.0004 μg/kg), approximately 96% of the body burden was 

eliminated with a half-time of 0.3 days (reflecting mainly excretion of unabsorbed tin in feces), and 4% 

was eliminated with a half-time of 3 days. 

Organotin Compounds. No studies were located regarding excretion in humans after oral exposure to 

organotin compounds. 

Methyltin Compounds. In rats, after a single oral dose of 3 mg/kg (1.8 mg Sn/kg; Brown et al. 1984), 

blood concentrations of trimethyltin decreased by one-half in approximately 3 days and, in brain, in 

approximately 2 (or less) days. Information identifying the relative contributions of various excretory 

routes for elimination of methyltin compounds was not located. 
TIN AND TIN COMPOUNDS 181 

3. HEALTH EFFECTS 

Ethyltin Compounds. Studies in rats indicate that urine and feces are the major routes of excretion of 

ethyltin following oral exposures to ethyltin compounds (Bridges et al. 1967). Over a 3-day period 

following a single oral dose of approximately 25 mg/kg ethyltin trichloride (12 mg Sn/kg), rats excreted 

92% (range 89–95%) of the dose in feces and 1.2% (range 1–2%) in urine (Bridges et al. 1967). 

Following absorption, ethyltin is excreted predominantly in urine, whereas absorbed diethyltin and 

triethyltin are excreted to a greater extent in feces (See Section 3.4.4.4). 

Butyltin Compounds. In mice that received a single oral dose of 1.2 mg/kg tri[14C]butyltin acetate, 

approximately 16% of the 14C dose was excreted in urine in 5 days, 53% was excreted in feces, and 22% 

was exhaled as [14C]CO2 (Kimmel et al. 1977). Following a similar dose di[14C]butyltin diacetate the 

excretion pattern (% of dose) was: urine, 10%; feces, 66%; and carbon dioxide, 7% (Kimmel et al. 1977). 

In mice, the amount of tin excreted in urine following an oral dose of different butyltins also increased 

with the number of butyl groups. Five days following a single oral dose of 180 μmol/kg of tri-, di-, or 

monobutyltin, urinary excretion of tin (percent of dose) was approximately: tributyltin, 5%; dibutyltin, 

3%; and butyltin, 0.3% (Ueno et al. 1994). These differences may reflect real differences in urinary 

excretion of absorbed tin compounds, or greater absorption of the tin compounds having a larger number 

of butyl groups. 

Phenyltin Compounds. Information or the rates or relative contributions of various excretory routes for 

elimination of phenyltin compounds was not located. 

3.4.4.3 Dermal Exposure 

No studies were located regarding excretion in humans or animals after dermal exposure to inorganic tin 

or organotin compounds. 

3.4.4.4 Other Routes of Exposure 

Inorganic Tin Compounds. Studies in which inorganic tin compounds have been parenterally injected 

into animals have shown that absorbed inorganic tin is excreted in urine and bile. Forty-eight hours after 

an intravenous injection to rats of 2 mg Sn/kg, as 113Sn [II] citrate, 35% of the administered radioactivity 

was excreted in urine and approximately 12% was (2 mg Sn/kg, as 113Sn [II] citrate) was excreted in the 

feces. In bile-duct cannulated rats, 23% was excreted in the urine, 11% in bile, and 2% in the feces. 

These observations indicate that urine and bile appear to be major routes of excretion of absorbed Sn[II]. 
TIN AND TIN COMPOUNDS 182 

3. HEALTH EFFECTS 

The biliary contribution to excretion of Sn[IV] was less than that of Sn[II], and after intravenous injection 

of 2 mg Sn/kg, as 113Sn [IV] citrate, 40% of the administered radioactivity was excreted in urine and 3% 

in feces. Following the same intravenous dose administered to rats that had bile duct cannulas, 25% of 

the administered dose was excreted in urine and 0.5% in bile (Hiles 1974). Urine-feces excretion ratios 

after intravenous injection of stannous chloride were approximately 10 in dogs, 3 in mice and rats, and 

5 in Rhesus monkeys (Furchner and Drake 1976). 

Rates of elimination of absorbed inorganic tin have been measured in mice, monkeys, rats, and dogs after 

intravenous or intraperitoneal injection of stannous chloride (Sn[II]Cl2) (Furchner and Drake 1976). 

Whole-body elimination kinetics of absorbed Sn[II] were similar in all four species and could be 

described with similar 4-compartment models. In Rhesus monkeys (dose, 0.0004 μg/kg), approximately 

39% of the body burden was eliminated with a half-time of 0.6 days, 11% was eliminated with a half-time 

of 5 days, 8% eliminated with a half-time of 24 days, and 42% was eliminated with a half-time of 

88 days. The pseudo-first order elimination half-times (all components combined) were approximately 

7 days in monkeys and 1–2 days in dogs, mice, and rats; the difference reflects the larger contribution of 

the slow compartment in the monkey (42%) compared to the other three species (20–30%). 

Measurements of the elimination kinetics of absorbed Sn[II], from individual tissues in rats (dose, 

0.006 μg/kg), suggested that bone was a major contributor to the slowest compartment, comprising 

approximately 50% of the body burden 1 day after dosing, and approximately 70–75% of the body burden 

from days 6–113 after dosing. Elimination rates were similar in all soft tissues measured (blood, brain, 

kidney, liver, spleen). These observations are consistent with the observations of accumulation of tin in 

bone with repeated exposures to Sn[II] compounds (Hiles 1974; NTP 1982; Yamaguchi et al. 1980). 

Methyltin Compounds. The elimination kinetics of tin from tissues, following parenteral injection of 

trimethyltin has been investigated in the rat. Cook et al. (1984a) administered single intraperitoneal doses 

of 6 mg/kg trimethyltin bromide (4.4 mg Sn/kg) to rats and measured tissue tin over 22 days following the 

dose. The pseudo-first order elimination half-times for tin were: blood, 10 days; brain, 10 days; heart, 

11 days; kidney, 12 days; and liver, 15 days. These rates were slower than those estimated for tin 

following a dose of triethyltin (Cook et al. 1984a). Ekuta et al. (1998) derived empirical, singlecompartment models of the kinetics of 14C in blood of four inbred mouse strains following single 

intraperitoneal injections of tri[14C]methyltin. Elimination half-times were 28.5 hours (AKR/J), 

31.3 hours (BalbcByJ), 30.0 hours (C57Bi6J), and 57.4 hours (DBA/2J). 
TIN AND TIN COMPOUNDS 183 

3. HEALTH EFFECTS 

Ethyltin Compounds. Following absorption, ethyltin is excreted predominantly in urine, whereas 

absorbed diethyltin is excreted to a much greater extent in feces. In rats, during the 72-hour period 

following an intraperitoneal dose of 12.7 mg/kg ethyltin trichloride (6 mg Sn/kg), 73% of the dose was 

excreted in urine and none in feces; approximately 4% of the dose was secreted into bile (Bridges et al. 

1967). Biliary secretion appears to be quantitatively more important in the excretion of absorbed 

diethyltin, compared to ethyltin. During the 72 hours following an intraperitoneal dose of 10 mg/kg 

[

14C]diethyltin dichloride (5 mg Sn/kg), approximately 64% of the administered dose of tin was excreted 

in feces and 31% in urine (fecal:urine ratio, 2.2); 32% of the administered 14C was excreted in feces and 

19% in urine (fecal:urine ratio, 1.8). In rats in which the bile duct had been cannulated, 56% of an 

intraperitoneal dose of [14C]diethyltin was secreted into bile; essentially all of the 14C secreted into bile 

was identified as diethyltin. Biliary secretion of triethyltin has also been observed in hamsters and guinea 

pigs, following intraperitoneal injection of 10 mg/kg triethyl[113Sn]tin chloride (5 mg Sn/kg) (Rose and 

Aldridge 1968). 

In rats, absorbed tetraethyltin appears to be excreted primarily as the trialkyltin metabolite. During the 

3 days following a subcutaneous dose of 10 mg/kg triethyltin in rats, approximately 0.20% of the dose 

was excreted in urine and 0.08% in feces (urine:feces ratio, 2.5; Iwai et al. 1982b). During the 3 days 

following a subcutaneous dose of 10 mg/kg tetraethyltin in rats, approximately 0.13% of the dose was 

excreted in urine and 0.07% in feces (urine:feces ratio, 1.9); however, no tetraethyltin was detected in 

excreta. 

The elimination kinetics of tin from tissues, following parenteral injection of triethyltin has been 

investigated in the rat. Cook et al. (1984a) administered single intraperitoneal doses of 6 mg/kg triethyltin 

as the bromide salt (3.5 mg Sn/kg) to rats and measured tissue tin levels over 22 days following the dose. 

The pseudo-first-order elimination half-times for tin were: blood, 2.5 days; brain, 4.6 days; heart, 

3.4 days; kidney, 5.6 days; and liver, 6.1 days. These estimates are consistent with rates of decline in tin 

levels measured in blood, brain, kidney, and liver 1–5 days following a single intravenous dose of 

10 mg/kg triethyl[113Sn]tin chloride (5 mg Sn/kg) in rats (Rose and Aldridge 1968). 

Butyltin Compounds. In rats, absorbed tetrabutyltin appears to be excreted as the trialkyltin metabolite. 

In rats, during the 3 days following a subcutaneous dose of 10 mg/kg tributyltin, approximately 0.18% of 

the dose was excreted in urine and 0.04% in feces (urine:feces ratio, 4.5; Iwai et al. 1982b). Following 

the same subcutaneous dose of tetrabutyltin, approximately 0.12% of the dose was excreted in urine and 

0.16% in feces (urine:feces ratio, 0.8); however, no tetrabutyltin was detected in excreta. 
TIN AND TIN COMPOUNDS 184 

3. HEALTH EFFECTS 

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 

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) are 
TIN AND TIN COMPOUNDS 185 

3. HEALTH EFFECTS 

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 3-9 shows a conceptualized representation of a PBPK model. 

If PBPK models for tin and tin compounds exist, the overall results and individual models are discussed 

in this section in terms of their use in risk assessment, tissue dosimetry, and dose, route, and species 

extrapolations. 

ICRP (1981b, 2001) Tin Biokinetics Model 

Description of the model. 

The ICRP (1981b, 2001) model is based on an empirical model developed by Furchner and Drake (1976) 

(Figure 3-10). The fraction of ingested tin that is absorbed from the gastrointestinal tract (uptake to 

blood) is assumed to be 0.02. Absorbed tin is assumed to enter the blood from where 50% is immediately 

transferred to excreta (specific routes not specified in the model), 35% is transferred to bone mineral, and 

15% is uniformly distributed to all other tissues. Tin in any tissue or organ is retained with elimination 

half-times of 4 (20% of tissue burden), 25 (20%), and 400 (60%) days. 

ICRP (1981b, 2001) also provides classifications for clearance of inhaled tin compounds in the 

respiratory tract, for use in the ICRP (1994) inhalation model. Sulphides, oxides, hydroxides, halides, and 

nitrates of tin, and stannic phosphate are assigned Type M; all other compounds of tin are assigned to 

Type F. For Type F compounds, rapid 100% absorption is assumed to occur within 10 minutes of 

material deposition in the bronchi (BB) bronchiole (bb), and alveolar interstitial (AI) regions. Fifty 

percent of Type F compounds deposited in extrathoracic region transfer to the gastrointestinal tract (ET2). 

During nose breathing, there is rapid absorption of approximately 25% of the tin deposited in the 
Inhaled chem ical E xhaled chem ical 

Lungs 

Liver 

Fat 

S low ly 

perfused 

tissues 

Richly 

perfused 

tissues 

K idney 

Skin 

V 

E 

N 

O 

U 

S 

B 

L 

O 

O 

D 

A 

R 

T 

E 

R 

I 

A 

L 

B 

L 

O 

O 

D 

V ma x K m 

Ingestion 

GI 

Tract 

Fe ces 

Urine

 C hem icals in air 

contacting skin 

TIN AND TIN COMPOUNDS 186 

3. HEALTH EFFECTS 

Figure 3-9. 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. 
Bone Mineral Blood Other Tissues 35% 15% 

20% 

*Elimination half -life 

Gastrointestinal Tract 

20% 

Excreta 

4 days* 

20% 

25 days* 

20% 

400 days* 

20% 

4 days* 

20% 

25 days* 

20% 

25 days* 

50% 

TIN AND TIN COMPOUNDS 187 

3. HEALTH EFFECTS 

Figure 3-10. ICRP (1981b, 2001) Tin Biokinetic Model 
 

TIN AND TIN COMPOUNDS 188 

3. HEALTH EFFECTS 

extrathoracic region, and 50% absorption during mouth breathing. For Type M compounds, 

approximately 70% of the tin deposited in AI eventually is transferred to blood and there is rapid 

absorption of about 10% of the tin deposited in BB and bb, and 5% of tin deposited in ET2. During nose 

breathing, approximately 2.5% of the deposit in ET is rapidly absorbed and 5% is rapidly absorbed during 

mouth breathing. 

Validation of the model. 

The extent to which the ICRP model has been validated is not described in ICRP (1981b). 

Risk assessment. 

The model has been used to establish radiation dose equivalents (Sv/Bq) of ingested and inhaled 

radioactive tin isotopes for ages 1 day to 50 years (ICRP 2001). 

Target tissues. 

The model is designed to calculate intake limits for radioactive tin, based on radiation dose to all major 

organs, including the bone surfaces, bone marrow, and liver, to which the highest doses would be 

expected. 

Species extrapolation. 

The model is designed for applications to human dosimetry and cannot be applied to other species without 

modification. 

Interroute extrapolation. 

The ingestion model (ICRP 1981b, 2001), together with the respiratory tract model (ICRP 1994) are 

designed to simulate oral and inhalation exposures to tin and cannot be applied to other routes of exposure 

without modification. 
TIN AND TIN COMPOUNDS 189 

3. HEALTH EFFECTS 

3.5 MECHANISMS OF ACTION 

3.5.1 Pharmacokinetic Mechanisms 

Absorption. The mechanism(s) of absorption of inorganic and organotin compounds have not been 

elucidated. In rats, following five oral doses of 10 mg/kg/day of tetra- or triethyltin, or tetra- or 

tributyltin, the alkyltin in the gastrointestinal tract tissue was primarily associated with the duodenum and 

jejunum indicating that these may be sites of absorption (Iwai et al. 1982b). A recent study with the 

Caco-2 human intestinal cell-line suggested that, in general, butyltins have a low in vivo permeability 

(Azenha et al. 2004). The study also showed that the permeability pattern correlated with the in vivo 

toxicity (trialkyltin ! dialkyltin ! monoalkyltin). However, the accumulation pattern (dialkyltin !

trialkyltin ! monoalkyltin) was different than that of permeability, presumably due to the strong affinity 

of dibutyltin for dithiol groups. Finally, the permeability of monobutyltin and dibutyltin, but not that of 

tributyltin, was found to be dependent of the paracellular route status. 

Distribution. Inorganic tin deposits in bone mineral; however, the mechanisms for the uptake and 

retention in bone have not been elucidated. 

Species differences have been demonstrated in the distribution of methyltin and ethyltin compounds 

within whole blood. Rats show higher red blood cell:plasma concentration ratios than other species, 

including humans and nonhuman primates (Brown et al. 1984; Rose and Aldridge 1968). Uptake and 

retention of methyltin and ethyltin in red blood cells has been attributed to binding to hemoglobin; 

however, the mechanism for the difference has not been elucidated. When hemoglobin from rat red blood 

cells is incubated with triethyl[113Sn]tin, radioactivity was bound to hemoglobin with an apparent affinity 

constant of approximately 3.5x105

 M-1 (Rose 1969). The pH-dependence of binding is consistent with 

involvement of histidine residues in hemoglobin (Rose 1969). 

The subcellular distribution of tin, following parenterally-administered trimethyltin or triethyltin, has 

been examined in rats and guinea pigs (Cook et al. 1984a; Rose and Aldridge 1968). Fractionation of 

brain tissue from animals that received a single intraperitoneal dose of 6 mg/kg trimethyltin (4.3 mg 

Sn/kg), revealed that tin was associated with the crude mitochondrial and microsomal fractions and, 

within the crude mitochondrial fraction, tin was associated with myelin, synaptosomes, and mitochondria 

(Cook et al. 1984b). The concentration in the mitochondrial fraction increased over time, reaching a 

maximum of 5 days after the dose. Subcellular concentrations of tin were 4–20 times lower after the 

6 mg/kg dose of trimethyltin (4.3 mg Sn/kg), compared to the 6 mg/kg dose of triethyltin (2.5 mg Sn/kg). 
TIN AND TIN COMPOUNDS 190 

3. HEALTH EFFECTS 

The subcellular distribution of tin in kidney and liver was similar in rats and guinea pigs following a 

parenteral dose of triethyltin; however, differences were observed between the distribution in rat brain 

compared to kidney and liver (Rose and Aldridge 1968). In rats, 2 hours following a single intravenous 

dose of 10 mg/kg triethyl[113Sn]tin chloride (5 mg Sn/kg), approximately 60% of the 113Sn was associated 

with the 40,000 x g supernatant (cytosolic) fraction and approximately 13% was associated with the 

heavy mitochondrial fraction. In brain, approximately 32% was associated with the supernatant fraction 

and 40% with the heavy mitochondrial fraction. Cook et al. (1984b) also found tin associated with the 

crude mitochondrial (13,000 x g) fraction of rat brain after a single intraperitoneal dose of 6 mg/kg 

triethyltin bromide (2.5 mg Sn/kg). Subfractionation of the crude mitochondrial fraction on a Ficoll 

gradient revealed tin associated with the myelin, synaptosomes, and mitochondria. 

In a comparative study with rats, mice, and guinea pigs, the susceptibility to develop liver damage 

followed the order: mice ! rats ! guinea pigs (Ueno et al. 2003b). This appeared to be partly due to 

differences in metabolism of tributyltin and in the distribution of dibutyltin within cell organelles. In 

hepatocytes of mice treated with dibutyltin chloride, 41% of the dibutyltin was found in organelles 

compared to 27% in rats and 9% in guinea pigs (Ueno et al. 2003b). 

Metabolism. No information on speciation of inorganic tin after absorption was located; therefore, the 

extent to which Sn[II] and Sn[IV] are interconverted is unknown. The major metabolic pathways for 

alkyltin compounds include dealkylation and hydroxylation and further oxidation of the alkyl moieties 

(see Section 3.4.3). These reactions have been found to occur in the microsomal fraction of liver 

(including human liver), are dependent on reduced nicotinamide adenosine dinucleotide phosphate 

(NADPH), and are inhibited by carbon monoxide, suggesting involvement of cytochrome P-450 (Kimmel 

et al. 1977; Ohhira et al. 2003). For triphenyltin, CYP2C6 constitutes the principal CYP for dearylation 

in hepatic microsomes of rats (Ohhira et al. 2004). 

Several studies have examined the involvement of metabolism in the toxicity of some organotin 

compounds. Cases have been described in which metabolism can either increase or decrease the toxicity 

of these compounds. For example, studies in hamsters showed that pretreatment of the animals with the 

cytochrome P-450 inducer, phenobarbital (PB), suppressed the diabetogenic effects of triphenyltin 

compared to PB-untreated hamsters (Ohhira et al. 1999). Pretreatment with the CYP1A and 2A inducers 

E-naphthoflavone and 3-methylcholanthrene, was not as effective as PB in preventing the organotininduced hyperglycemia and hypertriglyceridemia. On the other hand, pretreatment with the 
TIN AND TIN COMPOUNDS 191 

3. HEALTH EFFECTS 

P-450 inhibitor, SKF-525A, increased the diabetogenic effects of triphenyltin (Ohhira et al. 2000). 

Overall, these findings suggested that the hyperglycemic toxicity of triphenyltin is due primarily to 

accumulation of the parent compound, triphenyltin, in the pancreas, and not to a metabolite. Studies by 

Ueno et al. (1995, 1997) showed that the liver toxicity of tributyltin chloride could be prevented by 

treatment of the mice with the cytochrome P-450 inhibitor SKF-525A and that pretreatment with the 

P-450 inducer, PB increased the toxicity of tributyltin. These results suggested that the liver toxicity of 

tributyltin is due to a metabolite, most likely dibutyltin. 

Excretion. Bile, feces, and urine are major routes of elimination of absorbed inorganic and organotin 

compounds (see Section 3.4.4.4). Information on the mechanisms of biliary secretion and urinary 

excretion of tin compounds was not located. 

3.5.2 Mechanisms of Toxicity 

Studies in laboratory animals have shown that exposure to tin and tin compounds can produce a wide 

array of effects, but it is unknown whether exposure of humans to levels of tin compounds found in the 

environment will cause similar effects. General mechanisms of neurotoxicity and immunotoxicity of 

organotin compounds are briefly discussed below, as effects on these two systems may cause the most 

concern following potential exposures of humans to these substances. Although exposure to toxic 

amounts of neurotoxic organotins is somewhat unlikely, studies with trimethyltin and triethyltin in 

animals have shown a very steep dose-response curve for these substances and similar severe effects have 

been observed following acute high exposure of humans. Exposure to immunotoxic organotins, such as 

tributyltin, is much more likely because of substances’ use and, environmental prevalence, based on 

monitoring data. 

Neurotoxicity. Trimethyltin has been shown to produce degenerative lesions in the hippocampus and 

associated structures of the limbic system (e.g., dentate gyrus) in nonhuman primates and in several 

rodent species (see Section 3.2.2.4; Koczyk 1996). The lesions have been characterized as neuronal cell 

apoptosis and are accompanied with astrocyte swelling and reactive gliosis (Aschner and Aschner 1992; 

Fiederowicz et al. 2001; Haga et al. 2002; Koczyk and Oderfeld-Nowak 2000; McCann et al. 1996; 

Monnet-Tschudi et al. 1995a, 1995b). The glial response may be secondary to the primary neuronal 

lesion or a direct effect of trimethyltin on glial cell activation. Glial cell activation has been observed in 

primary cultures of rat cortical astrocytes (Mizuhashi et al. 2000a, 2000b; Röhl et al. 2001) and in primary 

cultures of neuronal/glial cells (including hippocampal cells) at exposures that did not produce changes in 
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neuronal cells (Figiel and Fiedorowicz 2002; Monet-Tschudi et al. 1995a, 1995b), suggesting direct 

effects of trimethyltin on microglia. Glial cell activation could contribute to neuronal cell degeneration 

by local release of pro-inflammatory cytokines, tumor necrosis factor-Į, and/or interleukins (Bruccoleri et 

al. 1998; Harry et al. 2002; Maier et al. 1995; McPherson et al. 2003). Trimethyltin has also been shown 

to induce apoptosis (and necrosis at higher exposure concentrations) in primary cell cultures of rat 

neuronal cells and in other cell models, suggesting possible direct effects on neuronal cells (Gunasekar et 

al. 2001; Jenkins and Barone 2004; Thompson et al. 1996; Viviani et al. 1998). Specific gene products, 

stannin and calcitonin gene-related peptide, may render neurons more vulnerable to trimethyltin-induced 

apoptosis (Bulloch et al. 1999; Thompson et al. 1996; Toggas et al. 1992). Astrocyte swelling may be 

related to perturbation of the regulation of transmembrane potassium (or other solute) gradients (Aschner 

et al. 1992; Brand et al. 1997). 

Numerous functional disturbances, at the cellular level, have been observed in association with the 

trimethyltin neuropathology. These effects may be contributing mechanisms to the primary lesion or may 

represent secondary phenomena associated with neuronal cell loss. Trimethyltin has been shown to 

stimulate the neuronal release of and/or to decrease neuronal cell uptake of neurotransmitters in brain 

tissue, including aspartate, GABA, glutamate, norepinephrine, and serotonin (Aschner et al. 1992; Costa 

1985; Dawson et al. 1995; Doctor et al. 1982; Earley et al. 1992; Gass? et al. 2000; Naalsund and 

Fonnum 1986; Patterson et al. 1996). Such effects could give rise to imbalances in neuronal inhibition 

and excitation; however, their contributions as either primary or secondary mechanisms of trimethyltininduced neuronal degeneration and/or neurological impairment have not been established. 

In mice, exposure to trimethyltin decreases the expression of neural cell adhesion molecule (NCAM) and 

depresses NCAM levels in the hippocampus (Dey et al. 1994, 1997). NCAM functions by establishing 

intercellular contact between neurons (e.g., synaptogenesis) and in cell migration during the development 

of the nervous system. In mature mice, NCAM continues to be expressed in the hippocampus, where it 

appears to function in the acquisition and consolidation of memory. Thus, altered NCAM expression may 

contribute to trimethyltin-induced impairments in learning and memory. 

At doses of trimethyltin that produce loss of hippocampal neurons, expression of several neuropeptides 

(e.g., dynorphin, enkephalin, neuropeptide Y, somatostatin) and neuropeptide receptors (e.g., neuropeptide Y) are altered in affected areas of the brain (Ishikura et al. 2001, 2002; Sadamatsu et al. 1998; 

Tsunashima et al. 1998). Altered expression of enkephalin and dynorphin may be contributing 

mechanisms to trimethyltin-induced brain seizures (Ishikura et al. 2001). Trimethyltin also has been 
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shown to alter various factors in the lymbic system associated with the pathophysiology of Alzheimer’s 

disease (Nilsberth et al. 2002). 

Triethyltin induces an edema that is largely restricted to brain white matter (intramyelinic edema) in 

animal models without a prominent gliosis, in contrast to the reactive gliosis observed in trimethyltin 

toxicity (see Section 3.2.2.4). The mechanism for the intramyelinic edema observed in triethyltin 

neurotoxicity has not been established. Altered expression of myelin basic protein is an early event in the 

intralamellar vacuolization that precedes the development of intramyelinic edema (Veronesi et al. 1991a, 

1991b). Increased expression of various pro-inflammatory cytokines in affected areas also appears to 

coincide with vacuolization; these include tumor necrosis factor-, interleukin-1 , and monocyte 

chemoattractant protein 1- (Mehta et al. 1998). Results from a study with cultured oligodendrocytes, the 

myelin-forming cells of the central nervous system, suggested that triethyltin causes the onset of 

programmed cell death in oligodendrocytes, as indicated by DNA fragmentation (Stahnke and RichterLandsberg 2004). Programmed cell death was accompanied by induction of a heat shock protein, HSP32, 

an indicator of oxidative stress, and ERK1,2, a signal-regulated kinases known to be activated under 

conditions similar to those that induce HSP32 transcription. 

Immunotoxicity. Thymic atrophy produced by certain organotins, such as triphenyltin, tributyltin, 

dibutyltin, and dioctyltin compounds, involves a decrease in the number of cortical thymocytes, resulting 

in reduced thymus weight (see Section 3.2.2.3, Seinen and Willems 1976; Seinen et al. 1977a, 1977b). 

With prolonged exposure, T-cell-mediated immune responses are suppressed (Seinen et al. 1977b). Loss 

of thymocytes appears to involve suppression of proliferation of immature thymocytes and, at higher 

dosages, apoptosis of mature thymocytes (Bollo et al. 1996; Raffay and Cohen 1993). These appear to be 

direct effects on the thymus as both cytotoxicity and apoptosis have been observed in thymocyte cell 

cultures exposed to di- or tributyltin (Gennari et al. 1997, 2000, 2002a; Raffay et al. 1993; Umebayashi et 

al. 2004) and triphenyltin (Dacasto et al. 2001; Stridh et al. 1999b). Cytotoxicity of butyltin compounds 

in thymocyte cultures involves suppression of DNA and protein synthesis (Gennari et al. 2002a; Raffay et 

al. 1993), and also induction of the expression of genes involved in apoptosis, such as nur77, a 

transcription factor member of the steroid/thyroid hormone receptor superfamily (Gennari et al. 2002b). 

An early and, possibly, the initiating event of apoptosis is a rise in cytosolic ionized calcium (Ca2+) 

concentration, caused both by intracellular calcium stores as well as by disruption of calcium transport at 

the cell membrane (Chow et al. 1992; Corsini et al. 1997; Gennari et al. 2000; Oyama et al. 1991, 1994, 

2003). Disruption of the regulation of intracellular calcium levels and, possibly, direct effects on energy 

metabolism of mitochondria either contributes to or gives rise to the uncontrolled production of reactive 
 

 

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oxygen species, release of cytochrome c to the cytosol, and the proteolytic and nucleolytic cascade of 

apoptosis (Gennari et al. 2000; Okada et al. 2000). Modification of the cytoskeleton through 

Ca2+-independent disruption of F-actin may also contribute to DNA fragmentation (Chow and Orrenius 

1994. 

Alkyltin compounds, in particular butyltin compounds, suppress T-cell-mediated immune responses, 

including antibody formation against foreign antigens, delayed hypersensitivity reactions, and allograft 

rejection (see Section 3.2.2.3). These effects appear to result from suppression of proliferation of 

immature thymocytes (CD4-

CD8+) which would, otherwise, differentiate into mature T-cells possessing 

the complete antigen-recognizing T-cell receptor complex, resulting in lower numbers of circulating 

functional T-cells (Pieters et al. 1994b, 1994c). Suppression of lymphoproliferative responses to T- and 

B-cell mitogens also has been demonstrated for triphenyltin (Dacasto et al. 1994b, 2001a, 2001b). 

Direct effects on lymphocyte function may also contribute certain aspects of immune suppression 

observed in animals exposed to butyltin compounds, including decreased natural killer cell activity. In 

vitro, butyltin compounds suppress cytotoxic activity of human natural killer cells that function in the 

immune response to tumors and virally-infected cells (Whalen et al. 1999, 2000, 2002a, 2003). 

Mechanisms for suppression of killer cells appear to involve loss of cell surface receptors important for 

binding to target cells (Odman-Ghazi et al. 2003; Whalen et al. 2002b), possibly secondary to a loss of 

regulation of intracellular cAMP (Whalen and Loganathan 2001), and disruption of the transcription of 

genes for the cytotoxic proteins granzyme B and perforin (Thomas et al. 2004), which are proteins 

contained in granules released by NK cells. 

3.5.3 Animal-to-Human Extrapolations 

Although information is available to support development of models of toxicokinetics for various tin 

compounds in rodents and nonhuman primates (e.g., Rhesus monkey, marmoset), evaluation of such 

models for applications to predicting the toxicokinetics of tin in humans would be highly uncertain 

because of the near complete lack of observations in humans (see Section 3.12.2). In addition, studies 

conducted in animals suggest differences between nonhuman primates and rats in certain important 

features of the toxicokinetics of tin compounds. For example, the elimination kinetics of absorbed 

inorganic tin occurs more slowly in Rhesus monkeys than in rodents; this difference appears to be the 

result of a larger fraction of the tin body burden associated with the slowest kinetic compartment 

(presumably bone) in monkeys. Organotin compounds, in particular methyltin and ethyltin, accumulate 
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in red blood cells to a much greater extent in rats than in other species, including nonhuman primates 

(Brown et al. 1984; Rose and Aldridge 1968). Also, studies of several rodent species showed different 

sensitivities to liver toxicity induced by tri- and dibutyltin which were related to the subcellular 

distribution of dibutyltin in hepatocytes (Ueno et al. 2003a, 2003b). The susceptibilities followed the 

order: mice ! rats ! guinea pigs. Another case in which extrapolation from rats or mice to humans may 

not be appropriate is that represented by the biliary duct necrosis produced by some organotins. Bile duct 

necrosis following administration of dibutyltin occurred in rats, mice, and hamsters, species which unlike 

man, have common bile duct systems, but did not occur in rabbits, guinea pigs, hens, and cats, which 

have separate bile duct and pancreatic duct systems (Boyer 1989; Kimbrough 1976). Thus, some 

toxicities of organotins in some animal species are not directly extrapolatable to humans. 

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 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), and in 

1998, the EDSTAC 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, 
 

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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). 

In recent years, concern has been raised that many pesticides and industrial chemicals are endocrineactive compounds capable of having widespread effects on humans and wildlife (Crisp et al. 1998; Daston 

et al. 1997; Safe et al. 1997). Particular attention has been paid to the possibility of these compounds 

mimicking or antagonizing the action of estrogen and exhibiting antiandrogenic properties. Estrogen 

influences the growth, differentiation, and functioning of many target tissues, including female and male 

reproductive systems, such as mammary gland, uterus, vagina, ovary, testes, epididymis, and prostate. 

Another way that endocrine-active compounds can affect development is by acting on thyroid hormones. 

Thyroid hormones are essential for the normal development of the nervous system, lung, skeletal muscle, 

and possible other organs. The fetus is dependent on maternal thyroid hormones at least until the fetal 

thyroid begins to produce T4 and triiodothyronine (T3), which occurs in humans at approximately 16– 

2 weeks of gestation. 

Thus far, there is no evidence that tin and tin compounds are endocrine disruptors in humans at the levels 

found in the environment. 

No studies were located regarding endocrine disruption in humans following exposure to tin or tin 

compounds or regarding effects in animals following exposure to inorganic tin. 

Inorganic Tin Compounds. The only relevant information located regarding inorganic tin is that 

stannous chloride induced the growth of MCF-7 breast cancer cells in vitro, decreased the steady-state 

amount of estrogen receptor protein and mRNA, induced the two estrogen-regulated genes, progesterone 

receptor and pS2, and activated the estrogen receptor in transient transfection experiments (Martin et al. 

2003). Tin exhibited 1/3 to 1/4 the estrogenic potency of estradiol when measured in MCF-7 cells 

transiently transfected with the luciferase reporter construct. 

Organotin Compounds. Intermediate- and chronic-oral studies with dibutyltin in rats and mice did not 

show alterations in the weight or in microscopic appearance of endocrine glands (Gaunt et al. 1968; NCI 

1978a; Seinen et al. 1977a). Dibutyltin dichloride, tributyltin chloride, and triphenyltin chloride induced 
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pre- and postimplantation loss and resorptions in rats when administered during pregnancy (Ema et al. 

1991b, 1995b, 1997b; Noda et al. 1991a, 1992). In all cases, the highest incidence of effects was 

observed when the chemicals were administered on Gds 7–9 (Ema et al. 1992, 1997a, 1999a). It was 

suggested that implantation loss that occurs after dosing the pregnant animals early during gestation is 

caused by an organotin-induced suppression of the uterine decidual cell response and decrease in 

progesterone levels (Ema and Miyawaki 2002; Ema et al. 1999b; Harazono and Ema 2000, 2003). 

Male ICR mice treated with 10 mg tributyltin oxide/kg 2 times/week for 4 weeks showed significantly 

reduced sperm counts (Kauasaka et al. 2002). In addition, light microscopy of the testis revealed 

disorganized seminiferous tubules with vacuolization of Sertoli cells and some loss of germ cells. No 

effects were seen on spermatogonia, spermatocytes, spermatids, Leydig cells, or the basement membrane 

of the seminiferous tubules; the study NOAEL was 2 mg/kg/day. A 2-year study with tributyltin oxide 

did not report histopathological alterations in endocrine glands from male and female rats treated with up 

to 2.1 mg/kg/day, except for a decrease in thyroid follicular epithelial cell height observed at 12 and 

24 months (Wester et al. 1990). However, no significant alterations were observed at 12 and 24 months 

in serum levels of TSH, LH, FSH, insulin, T4, or FT4. Chronic-duration studies with dibutyltin diacetate 

found no significant histopathological alterations in endocrine glands from rats and mice treated with 

dietary doses of up to 6.7 and 19.8 mg/kg/day, respectively, for 78 weeks (NCI 1978a). However, a longterm study with triphenyltin hydroxide reported an increase in Leydig cell hyperplasia and tubular atrophy 

of the testes in rats dosed with 5.2 mg/kg/day for 2 years (Tennekes et al. 1989b). This was not seen in 

rats dosed with up to 9.8 mg/kg/day or in mice dosed with up to 3.8 mg/kg/day for 78 weeks (NCI 

1978b). 

In male Fischer-344 rats treated with a single dose of 100 mg/kg of tributyltin oxide, there was an 

increase in serum cortisol and adrenal hypertrophy (Funahashi et al. 1980). Tributyltin oxide also 

significantly reduced serum T4 and TSH, but at the same time increased the stainability of TSH cells, 

suggesting that tributyltin oxide inhibited TSH release, which caused thyroid hypofunction. Since the 

decrease in circulating T4 was much more pronounced than that of TSH, Funahashi et al. (1980) 

suggested that tributyltin oxide also has a direct effect on the thyroid. Most acute effects appeared to be 

reversible within 14 days. Treatment of rats with 6 mg/kg/day for 26 weeks increased adrenal and 

hypophysis weight and also caused signs of thyroid hypofunction (Funahashi et al. 1980). In an 

additional intermediate-duration study with tributyltin oxide, treatment of Wistar rats with doses of 

approximately 4 mg/kg/day significantly decreased serum levels of T4 and TSH, and increased LH 

(Krajnc et al. 1984). No significant changes were measured in the concentrations of follicle-stimulating 
 

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3. HEALTH EFFECTS 

hormone (FSH) and corticosterone. Release of TSH after administration of thyrotropin-releasing 

hormone (TRH) was slightly reduced at 4 mg/kg/day, but releases of both LH and FSH were enhanced. 

Light microscopy revealed flattening of the epithelial lining of the thyroid follicles at 4 mg/kg/day, but 

not at lower doses. In the pituitary, treatment with 4 mg/kg/day tributyltin oxide reduced the number of 

TSH-immunoreactive cells and the staining intensity, increased the number of cells staining for LH, and 

had no significant effect in the staining for GH-, FSH-, or ACTH-producing cells. Krajnc et al. (1984) 

concluded that their results suggested that treatment with tributyltin oxide for 6 weeks did not stimulate 

the pituitary-adrenal axis. 

In a 2-generation reproductive toxicity study in female Wistar rats, there was suggestive evidence that 

tributyltin chloride may alter developmental landmarks controlled by sex hormones. Doses of 

10 mg/kg/day significantly delayed the day of eye opening in F2 pups (Ogata et al. 2001). Anogenital 

distance was significantly increased in F1 and F2 females on Pnds 1 and 4 and on Pnd 1 in F1 pups at 

2 mg/kg/day. The day of vaginal opening was significantly delayed (6 days) with 10 mg/kg/day in F1 and 

F2 groups. Analysis of the estrous cycles between Pnds 71 and 92 showed no alterations in F1 rats, but the 

number of cycles was significantly decreased in F2 rats. Also, the percentage of normal cycles was 

decreased F1 and F2 rats dosed with 10 mg/kg/day. 

A study of similar design with tributyltin chloride was conducted to evaluate the development of 

reproductive parameters in male Wistar rats (Omura et al. 2001). The doses tested were 0.4, 2, and 

10 mg/kg/day. Anogenital distance (measured on Pnds 1 and 4) was not significantly altered in F1 or F2 

males and neither was the day of testes descent. The day of eye opening was significantly delayed in 

mid- and high-dose F1 rats and in high-dose F2 rats. Effects on the weight of the sex organs included: 

decreased absolute testis weight in all F1 groups (dose-related); decrease absolute epididymis weight in 

low- and high-dose F1 groups; decrease absolute testis and epididymis weight in high-dose F2 groups and 

in relative prostate weight in mid- and high-dose F2 groups. The only sperm parameters that were 

significantly altered were sperm count in high-dose F2 rats and spermatid count in mid- and high-dose F2 

rats and high-dose F1 rats. Histological examination of the testes revealed minimal alterations in highdose F1 rats, but were more frequent and severe in F2 rats and were considered abnormal in this group. 

These effects consisted of vacuolization of the seminiferous epithelium, spermatid retention, and delayed 

spermiation. Serum testosterone was increased and estradiol was decreased in high-dose F1 rats; serum 

estradiol was decreased and LH was increased in high-dose F2 rats. 
 

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The information available is insufficient to ascertain whether organotins cause endocrine disruption in 

laboratory mammals, but the studies of Ogata et al. (2001) and Omura et al. (2001) suggest that tributyltin 

may have such a property. In addition, assays in vitro support this hypothesis. A brief summary of some 

recent in vitro studies is presented below. 

A commonly used test of potential endocrine-disruption activity is the assay of aromatase activity. 

Aromatase cytochrome P-450 is an enzyme that catalyzes the conversion of androgens to estrogens. 

Because estrogens are involved in processes including development of female secondary characteristics, 

regulation of bone density, menstruation cycle, and spermatogenesis, interference with their metabolism 

can have widespread consequences. Using human term placenta as source of enzymes, Heidrich et al. 

(2001) evaluated the aromatase activity of a series of organotins. The results showed that tributyltin 

chloride was a partial competitive inhibitor of aromatase activity. Dibutyltin dichloride was a less potent 

inhibitor, whereas tetrabutyltin and monobutyltin trichloride had no significant effect. In contrast, 

tributyltin had only moderate inhibitory activity toward 3E-HSD type I activity, an enzyme that converts 

dehydroepiandrosterone to androstenedione. None of the other butyltins tested inhibited 3E-HSD type I 

activity. Cooke (2002) found that tributyltin chloride and dibutyltin dichloride inhibited aromatase 

activity (a commercial preparation), but not monobutyltin or mono-, di-, or trioctyltins. 

Tributyltin chloride inhibited human 5D-reductase type1 and 5D-reductase type 2 (Doering et al. 2002), 

enzymes that mediate the activation of androgens, suggesting that this organotin could potentially disturb 

normal male reproductive physiology. 5D-Reductase type 2 also was inhibited by dibutyltin dichloride 

and neither enzyme was affected by monobutyltin trichloride or by tetrabutyltin, which suggested that at 

least two butyl groups bound to tin are required for the interaction with these enzymes. Triphenyltin 

chloride also was found to be a significant inhibitor of human sex steroid hormone metabolism by 

interacting with critical cysteine residues of the enzymes (Lo et al. 2003). McVey and Cooke (2003) 

examined the effects of organotins on the activity of 3E-hydroxysteroid dehydrogenase (3E-HSD), 

17-hydroxylase (17-OHase), and 17E-hydroxysteroid dehydrogenase (17E-HSD), enzymes that catalyze 

steps in the synthesis of steroids. In microsomes from rat testes, tributyltin chloride inhibited 17-OHase 

and 3E-HSD, whereas monooctyltin trichloride inhibited only 3E-HSD. 17E-HSD activity was unaffected 

by mono-, di-, or tributyltin, or mono-, di-, or trioctyltin. Triphenyltin chloride, tributyltin chloride, and 

dibutyltin dichloride suppressed testosterone production in Leydig cells in vitro from neonatal pig testes 

by a yet unknown mechanism (Nakajima et al. 2003). 
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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 

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). 
TIN AND TIN COMPOUNDS 201 

3. HEALTH EFFECTS 

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). 

No studies were located that specifically addressed exposure to inorganic tin in children. Data in adults 

regarding exposure to inorganic tin are derived from occupational exposure settings (a nonrelevant 

exposure scenario for children) and from ingesting food items contaminated with tin. This has produced 

nausea, vomiting, and diarrhea (WHO 1980, 2003) and it is expected that children would experience the 

same types of effects if exposed to high amounts of inorganic tin in the same manner. In a small number 

of studies available, exposure of rodents to inorganic tin during gestation did not result in embryotoxicity 

or teratogenicity (FDA 1972; Theuer et al. 1971). 

No specific information was found regarding exposure of children to organotins. The only information 

that involves exposure to children is that from a report by Wax and Dockstader (1995) indicating that all 

members of a family of five, including three children, complained of nausea, vomiting, headache, sore 

throat, burning nose, and wheezing 24 hours after a room in their home had been painted with a paint 

containing tributyltin oxide for mildew control. 

Studies in animals indicate that tributyltins, dibutyltins, and dioctyltins are mainly immunotoxic, whereas 

trimethyltins and triethyltins are neurotoxic. No studies of immunotoxicity in humans exposed to 

organotins have been conducted. A study in rats observed that the immunological effects produced by 

dibutyltin dichloride were more pronounced in rats exposed in the developmental phase of the lymphoid 

system (Seinen et al. 1977b). The neurotoxic effects of trimethyltin, triethyltin, and triphenyltin observed 

in experimental animals have been observed in adult humans accidentally exposed to these substances 

(Colosio et al. 1991; Feldman et al. 1993; Fortemps et al. 1978; Lin et al. 1998; Ross et al. 1981; Wu et 

al. 1990; Yanofsky et al. 1991) and it is reasonable to assume that similar types of effects would occur in 

children acutely exposed to high amounts of these substances. Studies with trimethyltin in rats showed 

that the development of lesions in the developing hippocampus is age-dependent and the most vulnerable 
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age period is between Pnds 9 and 15 (Chang 1984a, 1984b). Organotins are also known to be skin and 

eye irritants in adult humans (Goh 1985; Lyle 1958; Sheldon 1975) and similar effects would be expected 

in exposed children. 

There are no developmental studies of organotins in humans. However, studies in animals have shown 

that triphenyltin, dibutyltin, and tributyltin administered to rodents during pregnancy induce adverse 

developmental effects and that the severity of the effects depends of the specific day(s) of gestation when 

treatment occurs (Baroncelli et al. 1995; Ema et al. 1991a, 1991b, 1992, 1995b, 1997b; Faqi et al. 1997; 

Farr et al. 2001; Harazono et al. 1998; Noda et al. 1991a, 1991b). The most commonly seen 

malformations are facial malformations, particularly cleft plate. These studies also showed that 

organotins can induce adverse reproductive effects such as pre- and postimplantation losses, resorptions, 

and fetal deaths. One key issue not yet resolved is whether these effects occur secondary to maternal 

toxicity or can occur in the absence of maternal toxicity. 

Perinatal administration of organotins can cause neurodevelopmental (neurochemical and behavioral) 

effects in animals, which vary with the age at treatment and can persist until adulthood. This has been 

studied mostly with triethyltin and trimethyltin with the chemicals administered parenterally (Barone 

1993; Barone et al. 1995; Freeman et al. 1994; Miller and O’Callaghan 1984; O’Callaghan and Miller 

1988a; Reiter et al. 1981; Stanton 1991; Stanton et al. 1991). 

There is no information regarding the pharmacokinetics of tin and tin compounds in children. Studies in 

animals have shown that both inorganic tin (Theuer et al. 1971) and organotin compounds (Nakamura et 

al. 1993; Noda et al. 1994) can cross the placenta and reach the developing organism. There are no data 

on tin and tin compounds in human breast milk and no animal studies that have conclusively 

demonstrated transfer of tin and tin compounds to the offspring via maternal milk. Recently, Cooke et al. 

(2004) found negligible transfer of tributyltin and dibutyltin from rats dosed during lactation with up to 

2.5 mg tributyltin/kg/day to the pups via the milk. 

In two multi-generation studies in rats, exposure to tributyltin chloride induced slight alterations in 

developmental landmarks in male and female animals, suggesting the possibility that this substance 

possesses endocrine modulatory properties in mammals (Ogata et al. 2001; Omura et al. 2001). However, 

no comprehensive testing has been done with tributyltin or other organotins in laboratory mammals. 

Tests in vitro indicate that organotins can affect the activities of enzymes involved in the synthesis of 
TIN AND TIN COMPOUNDS 203 

3. HEALTH EFFECTS 

male and female sex hormones, which could affect the balance of androgens and estrogens in the body of 

developing mammals (Cooke 2002; Doering et al. 2002; Heidrich et al. 2001; McVey and Cooke 2003). 

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 

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 tin and tin compounds 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 tin and tin compounds are discussed in Section 3.8.2. 
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3. HEALTH EFFECTS 

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 Tin and Tin Compounds 

Absorbed inorganic tin distributes to soft tissues and bone (see Sections 3.4.2.2 and 3.4.2.4). Elimination 

of inorganic tin from blood and other soft tissues is relatively rapid (half-time, 1–3 days in monkeys); 

therefore, acute exposure may be detectable as an elevation in blood tin levels only for a few days (see 

Section 3.4.4.4). Blood measurements may be suitable for detecting exposures of intermediate or chronic 

duration. Models that would support quantitative estimates of exposure, based on blood tin levels, have 

not been developed. Inorganic tin is retained in bone for much longer periods (half-time, 2–3 months in 

monkeys); however, noninvasive methods for measuring elevations in bone tin levels are not available. 

Absorbed inorganic tin is excreted primarily in urine (see Section 3.4.4.4); therefore, measurements of 

urinary tin may allow detection of long-term exposures to tin; however, models for translating this 

information into quantitative estimates of exposure have not been developed. 

Detection of exposures to specific organotin compounds requires measurements of the specific compound 

(and metabolites). Organic tin compounds (alkyltin compounds) appear to be eliminated relatively 

rapidly from blood and other soft tissues (half-times, 2–15 days in rats); therefore, detection of exposure 

from measurements of alkyltin compounds in blood would require measurements made within a few days 

of an acute exposure (see Section 3.4.4.4). Models for estimating exposure levels from blood 

measurements have not been developed. Since absorbed alkyltin compounds are excreted in urine, 

urinary measurements may provide a means for detecting exposures. Methods for determining tin and tin 

compounds in biological materials are discussed in Section 7.1. 

3.8.2 Biomarkers Used to Characterize Effects Caused by Tin and Tin Compounds 

There are no specific biomarkers of effects for inorganic tin compounds. Certain organotin compounds 

do produce more specific effects than inorganic tin compounds. For example, studies in animals have 

shown that trimethyltin and triethyltin are primarily neurotoxic and affect specific areas or morphological 

substrates in the central nervous system (Aschner and Aschner 1992; Chang 1990). The structural 
 

TIN AND TIN COMPOUNDS 205 

3. HEALTH EFFECTS 

alterations observed in the brain from intoxicated animals (hippocampal lesions, intramyelinic edema) 

have also been observed in humans acutely exposed to high amounts of trimethyltin and triethyltin 

(Feldman et al. 1993; Foncin and Gruner 1979; Kreyberg et al. 1992; Yanofsky et al. 1991). Certain 

behavioral alterations seen in intoxicated animals, such as memory deficits and aggressive behavior, also 

have been observed in humans acutely exposed to high amounts of trimethyltin. While the neurological 

effects induced by these substances cannot be considered specific biomarkers of exposure for this group 

of chemicals, their manifestation can direct trained professionals to investigate potential exposure. 

Studies with other organotins, such as tributyltin, dibutyltin, and dioctyltin, in animals have reported 

effects on the bile duct and liver, immune system (thymus and lymphoid organs), kidneys, and blood, but 

these effects are not specific for organotin compounds. 

3.9 INTERACTIONS WITH OTHER CHEMICALS 

Tin is an element that affects the metabolism of various essential minerals such as zinc, copper, and iron 

by mechanisms not totally elucidated, but that may involve effects on absorption and retention. For 

example, Yamaguchi et al. (1979) reported that the increase in serum calcium concentration that occurred 

in rats following administration of a single oral dose of calcium chloride was significantly inhibited by 

previous administration of tin as stannous chloride (30 mg/kg every 12 hours for 3 days). Since calcium 

in the duodenal mucosa was reduced and the activity of alkaline phosphatase was also reduced in the 

mucosa, Yamaguchi et al. (1979) suggested that tin inhibited the duodenal active transport of calcium. In 

a study in volunteers, consumption of a diet that provided approximately 5 times more tin (0.65 mg 

Sn/kg/day) than a control diet (0.14 mg Sn/kg/day) for 20 days had no significant effect on fecal losses, 

urinary losses, apparent retention, and serum levels of calcium (Johnson and Greger 1982). 

Administration of tin (as stannous chloride) in the diet (200 ppm for 21 days) to rats resulted in reduced 

concentration of zinc in the tibias, reduced retention of zinc in the kidneys, and increased amounts of zinc 

in the feces (Greger and Johnson 1981). In addition, the copper content of the kidneys and liver of the 

animals fed the diet with added tin was significantly lower than in rats fed a control diet. Also in the 

Greger and Johnson (1981) study, tin had no effect on the retention of iron in the kidneys or in fecal 

losses of iron, but the concentration of iron in the livers from treated rats was significantly higher than in 

livers from control rats. The effect on zinc appeared to be, at least in part, due to reduced absorption of 

zinc since food intake was not depressed in the treated rats. In contrast, the effect of tin on copper status 

seemed to be caused by a different mechanism based on the fact that the tin diet did not increase fecal 

excretion of copper. Greger and Johnson (1981) suggested that the increase in liver iron could indicate an 
TIN AND TIN COMPOUNDS 206 

3. HEALTH EFFECTS 

improvement in the iron nutritional status of the rats or impairment in the rat’s abilities to mobilize iron 

from the liver. They further hypothesized that the effect of tin on iron metabolism may have been a 

reflection of the effect of tin on copper metabolism because ceruloplasmin, a copper metalloenzyme, is 

one enzyme involved in mobilization of iron from the liver. In a subsequent study, the same group of 

investigators showed that feeding rats diets containing >500 ppm tin reduced plasma copper levels to 13% 

of those in control rats and also depressed copper levels in kidneys and liver (Johnson and Greger 1985). 

Similar results regarding the effects of tin on copper and zinc metabolism were reported by Rader et al. 

(1990). The results of these studies are consistent with the findings of De Groot (1973), who observed 

that supplementation of a high-tin diet with copper and iron could reduce signs of anemia in rats, but 

could not correct the reduced growth, and reduced growth is a common symptom of zinc deficiency 

(Rader et al. 1990). Tin was also found to interact with zinc metabolism in humans; individuals fed diets 

with excess tin lost significantly more zinc in their feces and less zinc in the urine than those fed a control 

diet (Johnson et al. 1982). 

In a study in rats, Noda et al. (1994) examined the effect of pretreatment of pregnant animals with carbon 

tetrachloride on the teratogenic activity of dibutyltin dichloride. Pregnant rats were treated 

subcutaneously with carbon tetrachloride on Gds 6 and 7 and orally with various dose levels of dibutyltin 

dichloride on Gd 8; sacrifices were conducted on Gd 20. Pretreatment with carbon tetrachloride 

significantly increased the incidence of external and skeletal malformations caused by the organotin 

alone. Moreover, pretreatment with carbon tetrachloride increased the concentration of dibutyltin in 

embryos, maternal liver, and blood. Carbon tetrachloride caused maternal hepatotoxicity (increased 

serum transaminases) and decreased the activity of hepatic microsomal drug-metabolizing enzymes, 

suggesting that dibutyltin itself (and not a metabolite) was teratogenic. 

Makita et al. (2003, 2004) studied the effects of the simultaneous administration of tributyltin chloride 

and p,p’-DDE on developmental end points in rats. Rats were treated orally with tributyltin 

chloride/kg/day alone (2 mg/kg/day) or tributyltin chloride plus p,p’-DDE (10 mg/kg/day) during 

gestation and lactation. Developmental parameters examined in the pups at various times up to 6 weeks 

of age included gender and gross malformations, body and sex organ weights, anogenital distance, eye 

opening, nipple retention (in males), vaginal opening, vaginal opening, preputial separation, and serum 

testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Tributyltin significantly 

depressed growth rate of the pups from Pnd 7 to 28, but simultaneous administration of p,p’-DDE 

prevented this effect. Sex organs’ weights were not affected by tributyltin, except for prostate weight 

which was decreased, but this decrease also was prevented by administration of p,p’-DDE. Ovary weight 
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was increased in the combination group relative to the tributyltin alone group. Serum testosterone was 

not affected in any group and serum LH was reduced in the tributyltin group, but not in the combination 

group. Tributyltin did not affect anogenital distance, nipple retention, or vaginal opening, but delayed eye 

opening (not observed in the combination group). The mechanism of interaction between tributyltin and 

p,p’-DDE is unknown. 

3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE 

A susceptible population will exhibit a different or enhanced response to tin and tin compounds than will 

most persons exposed to the same level of tin and tin compounds 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 tin and tin 

compounds, or compromised function of organs affected by tin and tin compounds. Populations who are 

at greater risk due to their unusually high exposure to tin and tin compounds are discussed in Section 6.7, 

Populations with Potentially High Exposures. 

There are no specific populations that have been identified as being unusually susceptible to inorganic tin 

compounds with respect to health effects. However, studies in animals and humans indicate that 

inorganic tin affects the metabolism of various essential trace elements. For example, levels of dietary tin 

much higher than those in normal diets reduce zinc absorption, which reduces growth, and reduces 

plasma copper levels, and may lead to anemia. Therefore, children or adults who consume diets already 

poor in these minerals may be at higher risk of developing signs of lack of zinc or copper if their dietary 

tin is excessive (as in a canned-food-based diet). However, it is important to note that >90% of tin-lined 

cans used for food today are lacquered. 

No population has been identified that is unusually susceptible to the effects of exposure to organotin 

compounds. 

3.11 METHODS FOR REDUCING TOXIC EFFECTS 

This section will describe clinical practice and research concerning methods for reducing toxic effects of 

exposure to tin and tin compounds. 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 tin 

and tin compounds. When specific exposures have occurred, poison control centers and medical 
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3. HEALTH EFFECTS 

toxicologists should be consulted for medical advice. No texts were found that provided specific 

information about treatment following exposures to tin and tin compounds. 

Human exposure to tin may occur by inhalation, ingestion, or dermal contact (see Chapter 6). 

Gastrointestinal effects have been observed following ingestion of inorganic tin compounds and 

inhalation, ingestion or dermal exposure to some organotin compounds may cause neurological effects 

(see Section 3.2). Inorganic tin salts and organotins are reported to be skin and eye irritants (WHO 1980). 

The information below has been extracted from HSDB (2003). 

3.11.1 Reducing Peak Absorption Following Exposure 

Usually, it is unnecessary to induce emesis in cases of ingestion of inorganic tin compounds, and induced 

emesis may be dangerous in patients who have ingested caustic tin compounds such as stannic chloride. 

Emesis is contraindicated following ingestion of trimethyltin. Immediate dilution with 4–8 ounces of 

milk or water is recommended after oral exposure, as well as administration of activated charcoal slurry 

(240 mL water/30 g charcoal). Following inhalation exposure, the patient should be moved to fresh air. 

In cases of dermal exposure, contaminated clothing should be removed and the exposed area should be 

washed thoroughly with soap and water. Irrigation with copious amounts of tepid water (or preferably a 

physiologically-balanced eye wash solution) for at least 15 minutes is recommended in cases of eye 

exposure. Gastric lavage can be considered after ingestion of a potentially life-threatening amount of a 

tin compound if it can be performed soon after ingestion (generally within 1 hour). Caution should be 

used to protect the airway by placement in Trendelburg and left lateral decubitus position or by 

endotracheal intubation. 

3.11.2 Reducing Body Burden 

No specific information was located to reduce the body burden of tin and compounds following exposure. 

3.11.3 Interfering with the Mechanism of Action for Toxic Effects 

Information summarized in HSDB (2003) describes standard measures to support vital functions 

following exposure. There are specific measures to interfere with the mechanism of toxicity of tin and 

compounds. Because the toxicity of dialkyltins is related to reactions with biological dithiol groups, BAL 
TIN AND TIN COMPOUNDS 209 

3. HEALTH EFFECTS 

(2,3-dimercaptopropanol) has been suggested as an antidote, based on studies in animals, but it was not 

effective against trialkyltins or tetraalkyltins. DMPS (2,3-dimercaptopropane-1-sulfonic acid) and DMSA 

(meso-2,3-dimercaptosuccinic acid) were effective in reducing the bile duct, pancreas, and liver lesions in 

rats, but were less effective against thymus atrophy (Merkord et al. 2000). 

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 tin and tin compounds 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 tin and tin compounds. 

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 Tin and Tin Compounds 

The existing data on health effects of inhalation, oral, and dermal exposure of humans and animals to tin 

and tin compounds are summarized in Figures 3-11 and 3-12. The purpose of this figure is to illustrate 

the existing information concerning the health effects of tin and tin compounds. 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. 
TIN AND TIN COMPOUNDS 210 

3. HEALTH EFFECTS 

Figure 3-11. Existing Information on Health Effects of Inorganic Tin Compounds 

Death

Acute 

Intermediate 

Chronic 

Immunologic/Lymphoretic 

Neurologic 

Reproductive 

Developmental 

Genotoxic 

Cancer 

Systemic 

Human 

Inhalation 

Oral 

Dermal 

Death

Acute 

Intermediate 

Chronic 

Immunologic/Lymphoretic 

Neurologic 

Reproductive 

Developmental 

Genotoxic 

Cancer 

Systemic 

Animal 

Inhalation 

Oral 

Dermal 

Existing Studies 
TIN AND TIN COMPOUNDS 211 

3. HEALTH EFFECTS 

Figure 3-12. Existing Information on Health Effects of Organotin Compounds 

Death

Acute 

Intermediate 

Chronic 

Immunologic/Lymphoretic 

Neurologic 

Reproductive 

Developmental 

Genotoxic 

Cancer 

Systemic 

Human 

Inhalation 

Oral 

Dermal 

Death

Acute 

Intermediate 

Chronic 

Immunologic/Lymphoretic 

Neurologic 

Reproductive 

Developmental 

Genotoxic 

Cancer 

Systemic 

Animal 

Inhalation 

Oral 

Dermal 

Existing Studies 
TIN AND TIN COMPOUNDS 212 

3. HEALTH EFFECTS 

Figure 3-11 provides the information for inorganic tin compounds. There are case reports that describe 

acute and chronic effects of inhaled inorganic tin compounds on humans. There are also reports of 

humans that developed health effects after oral exposure to food and drink from tin cans. No other 

studies were located regarding health effects in humans after inhalation, oral, or dermal routes of 

exposure. The most relevant route of exposure to inorganic tin for humans is the oral route. 

The health effects of inorganic tin compounds have been chiefly studied in animals after oral exposure, as 

shown in Figure 3-11. The figure also shows that no inhalation studies and only a few dermal studies 

were located regarding health effects from inorganic tin compounds. 

Figure 3-12 provides health effects information on humans and animals after exposure to organotin 

compounds. The database for these compounds as a class is much more complete than for the inorganic 

tin compounds. There are case reports that describe deaths and other effects associated with inhalation, 

oral, and dermal routes of exposure. In addition to acute-duration inhalation studies and acute and 

intermediate dermal studies, there are reports of neurobehavioral effects in humans after inhalation, oral, 

and dermal exposures. The main route of exposure to organotins for humans is the oral route. 

The extent of the database on health effects in animals resulting from exposure to organotin compounds is 

shown in Figure 3-12. Except for genotoxic studies, there are oral studies that describe all the other 

toxicological end points considered in this profile. By contrast, the information is more limited for the 

inhalation and dermal routes of exposure. 

3.12.2 Identification of Data Needs 

Acute-Duration Exposure. There are no data in humans following acute inhalation exposure to 

inorganic tin and the data in animals are limited mostly to death (Igarashi 1959; Schweinfurth and Gunzel 

1987). Therefore, an acute-duration inhalation MRL was not derived for inorganic tin. For organic tin 

compounds, limited acute inhalation data exist for death in humans (Rey et al. 1984) and in animals 

(Igarashi 1959; Schweinfurth and Gunzel 1987), systemic effects in humans (Rey et al. 1984; Saary and 

House 2002; Wax and Dockstader 1995) and in animals (Igarashi 1959), and neurological effects in 

humans (Feldman et al. 1993; Rey et al. 1984; Ross et al. 1981; Saary and House 2002; Yanofsky et al. 

1991). The information provided in these studies is inadequate for derivation of acute-duration inhalation 

MRLs for inorganic tin or organotins largely because of lack of quantitative data. Oral exposure is the 

main route of exposure to inorganic tin for humans. The available acute oral data for inorganic tin 
TIN AND TIN COMPOUNDS 213 

3. HEALTH EFFECTS 

provide information on lethality in animals (NTP 1982), on reproductive/developmental effects in rodents 

(FDA 1972), and on systemic effects in humans (Boogaard et al. 2003; WHO 1980, 2003). In the case of 

organotins, data exist for lethality in humans (Kreyberg et al. 1992; WHO 1980) and in animals (WHO 

1980), systemic effects in humans (Lin and Hsueh 1993; Lin et al. 1998; WHO 1980; Wu et al. 1990) and 

in animals (Barnes and Magee 1958; Pelikan and Cerny 1970; Raffray and Cohen 1993; Funahashi et al. 

1980; Seinen et al. 1977a; Takagi et al. 1992; Ueno et al. 1994, 1995, 1997, 2003a, 2003b), immunological effects in animals (Seinen et al. 1977a; Smialowicz et al. 1989, 1990; Snoeij et al. 1985), neurological effects in humans (Kreyberg et al. 1992; Lin et al. 1998; WHO 1980; Wu et al. 1990) and in 

animals (Baroncelli et al. 1990, 1995; Brown et al. 1984; Chang and Dyer 1983; Chang et al. 1983; Davis 

et al. 1987; Ema et al. 1991a; Magee et al. 1957; Squibb et al. 1980), and reproductive and developmental 

effects in animals (Ema and Harazono 2000; Ema et al. 1991b, 1992, 1997b, 1999b, 1999c, 2003; Farr et 

al. 2001; Harazono and Ema 2003; Noda et al. 1991a, 1992b). Again, the data for inorganic tin were 

insufficient for derivation of an acute oral MRL. The data for organotins were either insufficient or 

inadequate in that no NOAELs were available and most LOAELs were serious LOAELs, thus precluding 

derivation of acute oral MRLs. Acute dermal data were limited to a lethal human case (NIOSH 1976) and 

several reports in animals (Smith 1978) exposed to organotins, information on hepatic effects in humans 

(Colosio et al. 1991), and dermal and ocular effects in humans and animals (Barnes and Stoner 1958; Goh 

1985; Klimmer 1969; Lyle 1958; Sheldon 1975). Excessive acute exposure to inorganic tin is unlikely to 

occur unless there is consumption of unusually high amounts of canned foods in a short period of time. 

Further acute studies with inorganic tin are unlikely to provide new key information. The decision to 

expand the database for acute exposure to some organotin compounds should be based on the results of a 

case-by-case evaluation of the likelihood of potential exposure to high concentrations of these substances 

for people living near waste sites. It is unlikely that the general population will be acutely exposed to 

high amounts of organotins. 

Intermediate-Duration Exposure. There are currently no data concerning the effects of inorganic 

tin or organotin compounds on humans for this exposure duration for the inhalation, oral, or dermal routes 

of exposure. No data were available regarding effects in animals after intermediate-duration exposure to 

inorganic tin by the inhalation route. Studies of inorganic tin in rodents, primarily rats and mice, treated 

orally demonstrated effects in the gastrointestinal tract, the blood, the kidney, the liver, and bile ducts 

(Chmielnicka et al. 1993; De Groot et al. 1973; Dreef-van der Meulen et al. 1974; Janssen et al. 1985; 

NTP 1982; Schroeder et al. 1968). Very limited information was located regarding reproductive and 

developmental effects of inorganic tin compounds in animals (Theuer et al. 1971). The study by 

De Groot et al. (1973) with stannous chloride was used to derive an intermediate-duration oral MRL for 
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3. HEALTH EFFECTS 

inorganic tin. Few studies were located that tested organotin compounds by the inhalation route in 

animals. These studies provided some information on respiratory, hepatic, renal, and reproductive effects 

but lacked enough detail to be considered for MRL derivation (Gohlke et al. 1969; Igarashi 1959; 

Iwamoto 1960). Intermediate-duration oral exposure studies with organotins provide information on 

lethality in various species (Magee et al. 1957; NCI 1978b; Seinen et al. 1977b) and on a variety of end 

points (hematological, body weight, endocrine, hepatic, renal, immunological, neurological, reproductive, 

and developmental in rodents (Adeeko et al. 2003; Barnes and Magee 1958; Bouldin et al. 1981; Bressa et 

al. 1991; Carthew et al. 1992; Cooke et al. 2004; Dacasto et al. 1994a; Funahashi et al. 1990; Gaunt et al. 

1968; Graham and Gonatas 1973; Jang et al. 1986; Krajnc et al. 1984; Noland et al. 1982; Ogata et al. 

2001; Omura et al. 2001; Purves et al. 1991; Seinen and Willems 1976; Seinen et al. 1977a, 1977b; Smith 

1973; Snoeij et al. 1985; Tryphonas et al. 2004; Verdier et al. 1991; Vos et al. 1990). Most of these 

studies tested dibutyltin, dioctyltin, tributyltin, triethyltin, trimethyltin, and/or triphenyltin. Adequate 

information was available for derivation of an intermediate-duration oral MRL for dibutyltin dichloride 

based on altered humoral immune responses in rats (Seinen et al. 1977b) and for tributyltin oxide, also 

based on immunotoxicity (Vos et al. 1990). Information regarding effects following intermediateduration dermal exposure was restricted to a study by Sheldon (1975), who described skin alterations in 

rabbits during a 90-day exposure period. Oral exposure is the main route of exposure to inorganic tin for 

humans; therefore, inhalation and dermal exposure studies seem unnecessary. Also, further oral studies 

are unlikely to provide new information. The effects of some organotins (i.e., trimethyltin, triethyltin, 

tributyltin, dibutyltin) are well characterized. Still, the information available for trimethyltin and 

triethyltin was inadequate for MRL derivation, largely because of the steepness of the dose-response 

curve for these compounds. The decision to conduct additional intermediate-duration studies designed to 

define NOAELs should rest on results of monitoring studies for these compounds in the environment and 

on the identification of populations potentially exposed to them. 

Chronic-Duration Exposure and Cancer. Data on chronic exposure to inorganic tin were limited 

to cases of occupational exposures in which the main effects were respiratory effects (Cutter et al. 1949; 

Dundon and Hughes 1950; Pendergrass and Pryde 1948; Stewart and Lassiter 2001). Inhalation is 

assumed to have been the main route of exposure in these cases. Affected individuals showed a benign 

form of pneumoconiosis, or stannosis. Information regarding health effects in animals following chronicduration exposure to inorganic tin is restricted to a 2-year oral bioassay in rats and mice (NTP 1982), a 

42-month oral study in rats (Schroeder et al. 1968), and an 18-month oral study in mice (Schroeder and 

Balassa 1967), all with stannous chloride. While there were no compound-related nonneoplastic effects 

in the NTP (1982) study in rats and mice, Schroeder et al. (1968) described hepatic and renal effects as 
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3. HEALTH EFFECTS 

well as decreased longevity in rats exposed to doses approximately 100 times lower than those tested by 

NTP (1982). There is no apparent explanation for this discrepancy except that the NTP (1982) study was 

a dietary study, while Schroeder et al. (1968) administered the compound in the drinking water. Studies 

comparing the bioavailability of tin in solid food vs. water may provide useful information. No chronic 

oral MRL was derived for inorganic tin because the lowest dose from Schroeder et al. (1968) was a 

serious LOAEL. The need to conduct inhalation and dermal chronic-duration studies with inorganic tin is 

less clear since the main route of exposure for humans to inorganic tin is the oral route. No data were 

located regarding health effects in humans following chronic exposure to organotin compounds. Longterm bioassays have been conducted for dibutyltin diacetate in rats and mice (NCI 1978a), triphenyltin 

hydroxide in rats and mice (NCI 1978b; Tennekes et al. 1989a, 1989b), and tributyltin oxide in rats 

(Wester et al. 1990). In addition, an 18-month study of the immunotoxicity of tributyltin oxide in rats is 

available and was used as basis for deriving a chronic-duration oral MRL for tributyltin oxide (Vos et al. 

1990). No chronic oral MRL was derived for dibutyltin because a relative low dose in the NCI (1978a) 

study caused significant early mortality in rats. For the same reason, no chronic oral MRL was derived 

for triphenyltin (Tennekes et al. 1989b). Research to produce chronic oral data for other organotins that 

may be present in hazardous waste sites and represent a potential source of exposure for those living in 

the vicinity may be warranted. However, a comprehensive evaluation of 90-day studies should be 

conducted first. Environmental monitoring information suggests that the inhalation and dermal routes of 

exposure to organotins are much less relevant to humans than the oral route and, therefore, may be given 

lower priority. 

There is no information regarding cancer in humans exposed to inorganic tin or organic tin compounds. 

An oral bioassay for stannous chloride in rats and mice provided no evidence of carcinogenicity at the 

levels tested (NTP 1982). Similar negative results were found for dibutyltin diacetate in rats and mice, 

although technical problems did not allow for a complete evaluation of uterine tumors in female rats (NCI 

1978a). A bioassay for triphenyltin hydroxide in rats and mice also gave negative results (NCI 1978b), 

but studies with higher doses did find triphenyltin hydroxide to induce pituitary and testicular tumors in 

rats (Tennekes et al. 1989b) and hepatocellular carcinomas in mice (Tennekes et al. 1989a). A bioassay 

with tributyltin oxide in rats yielded questionable results (Wester et al. 1990), which led the EPA (IRIS 

2005) to assign this chemical to a group for which “there is inadequate information to assess carcinogenic 

potential.” Since the observed tumors were considered to have high incidence in the strain of rat used 

(Wistar), it may be necessary to repeat the study in a different strian of rat. An oral bioassay seems more 

relevant than inhalation or dermal studies since these two routes of exposure are less relevant for humans. 

Further studies concerning the fates of the organic and tin moieties from these compounds and the 
 

TIN AND TIN COMPOUNDS 216 

3. HEALTH EFFECTS 

contribution of each moiety to mechanisms of carcinogenicity are needed in order to evaluate the role of 

tin in the tumorigenic response. 

Genotoxicity. There are no human data regarding the genotoxic potential of inorganic tin or organotin 

compounds after inhalation, oral, or dermal exposures. The limited in vitro data for inorganic tin consist 

mostly of studies with stannous chloride and stannic chloride. The results in prokaryotic organisms have 

been mostly negative (Hamasaki et al. 1993; Nishioka 1975), but the opposite has been observed in tests 

conducted with mammalian cells (Dantas et al. 2002; Ganguly et al. 1992; Gulati et al. 1989). Further 

studies are unlikely to add new key information. Tests of many organotin compounds in S. typhimurium 

gave predominantly negative results (Hamasaki et al. 1993) and tests conducted in mammalian cells in 

vitro also gave predominantly negative results (Chao et al. 1999; Davis et al. 1987; Oshiro et al. 1991; 

Sasaki et al. 1993). Studies of organotin compounds in vivo, mostly in mice, have given mixed results 

(Chao et al. 1999; Davis et al. 1987; Ganguly 1994; Yamada and Sasaki 1993). Further genotoxicity 

studies with organotin compounds do not seem warranted at this time. 

Reproductive Toxicity. No studies were located regarding reproductive effects of inorganic tin in 

humans following inhalation, oral, or dermal exposure or in animals following inhalation or dermal 

exposure. The only information available regarding oral exposure of animals to inorganic tin is that from 

Theuer et al. (1971), FDA (1972), and De Groot et al. (1973). FDA (1972) reported no reproductive 

effects (number of corpora lutea and of implantation and resorption sites) in rats, mice, and hamsters 

administered up to 0.31 mg tin/kg/day (as stannous chloride) during gestation (Gds 6–15 for rats and 

mice, Gds 6–10 for hamsters) (FDA 1972). Theuer et al. (1971) reported that administration of tin, as tin 

fluoride or sodium pentachlorostannite, to rats in the diet during gestation had no significant effect on the 

number of resorptions or placental weight. De Groot et al. (1973) observed moderate testicular 

degeneration in rats dosed for 9 weeks with approximately 315 mg tin/kg/day. Most rats in this group 

were moribund and had to be sacrificed; therefore, the biological significance of the testicular finding is 

unclear. The limited data available suggest that the reproductive system is not a target for inorganic tin 

toxicity at the levels commonly found in the environment. No data were available regarding reproductive 

effects in humans following exposure to organotin compounds by any route or in animals after dermal 

exposure. Reduced fertility was reported in female rats following inhalation exposure to a mixture of 

tributyltin bromide and dibutyltin dibromide for periods ranging from a few weeks to a few months 

(Iwamoto 1960). Numerous studies in rodents have examined the effects of organotins (mostly 

dibutyltin, tributyltin, and triphenyltin) on reproductive parameters such as pregnancy rates, pre- and 

postimplantation loss, and fetal deaths following dosing during pregnancy (Adeeko et al. 2003; Ema and 
 

TIN AND TIN COMPOUNDS 217 

3. HEALTH EFFECTS 

Harazono 2000; Ema et al. 1991b, 1992, 1999c; Faqi et al. 1997; Harazono et al. 1998; Noda et al. 1991a, 

1992b) and found that the highest incidence of resorptions and postimplantation losses occurred when the 

chemicals were administered on Gds 7–9 (Ema et al. 1992, 1997a, 1999a). Most long-term studies have 

not reported histopathological alterations in reproductive organs from rats or mice (NCI 1978a, 1978b; 

Wester et al. 1990) with the exception of Tennekes et al. (1989b), who reported an increase in Leydig cell 

hyperplasia and tubular atrophy of the testes in rats treated with triphenyltin. The mechanism by which 

some organotins affect reproduction is not known, but there is evidence that suppression of uterine 

decidualization may be a cause of preimplantation losses (Ema and Miyawaki 2002; Ema et al. 1999b; 

Harazono and Ema 2003). It would be helpful to elucidate whether effects such as pre- and 

postimplantation loss occur secondary to maternal toxicity or can happen independent of maternal 

toxicity. Since direct effects on reproductive organs do not seem to have an important role (except for the 

findings of Tennekes et al. 1989b), further research should focus on the effects of organotins on the 

endocrine control of reproductive functions in adult animals and on the hormonally-controlled 

development of reproductive organs in animals exposed in utero and early in life. Numerous studies in 

vitro have shown that organotins can affect the activities of enzymes involved in the synthesis of steroid 

hormones, with potentially widespread consequences (i.e., Cooke 2002; Doering et al. 2002; Heidrich et 

al. 2001; McVey and Cooke 2003). Additional tests to evaluate the potential endocrine disrupting ability 

of organotins in mammals should be conducted. Pilot studies in primates would be valuable to reduce the 

uncertainty of extrapolating observations in animals to human health. 

Developmental Toxicity. No studies were located regarding developmental effects of inorganic tin 

in humans following inhalation, oral, or dermal exposure, or in animals following inhalation or dermal 

exposure. Limited oral data on inorganic tin showed that treatment of rats, mice, and hamsters with up to 

31 mg tin/kg/day by gavage in water during gestation (Gds 6–15 for mice and rats, Gds 6–10 for 

hamsters) has no significant effect on fetal weight, the number of live of dead fetuses, or the incidence of 

external and internal malformations (FDA 1972). Also, tin, in the form of tin fluoride or sodium 

pentachlorostannite, administered to rats during pregnancy had no significant effect on average fetal 

weight or the number of live fetuses per litter (Theuer et al. 1971). This study also showed that tin from 

inorganic compounds can cross the placenta and reach the fetus. There are no studies of developmental 

effects in humans following inhalation, oral, or dermal exposure to organotins. Several studies in 

animals, mostly rats and mice, have shown that oral exposure to some organotin compounds (mostly 

tributyltin, dibutyltin, and triphenyltin) during pregnancy induces external and skeletal malformations, the 

most common of which were cleft jaw and ankyloglossia (Ema and Harazono 2000; Ema et al. 1991b, 

1992; Faqi et al. 1997; Harazono et al. 1998; Noda et al. 1991a, 1992b) and found that the highest 
TIN AND TIN COMPOUNDS 218 

3. HEALTH EFFECTS 

incidence of malformations occurred when the chemicals were administered on Gds 7–9 (Ema et al. 

1992). Limited data in rats indicate that dibutyltin can cross the placenta and reach the embryo 

(Nakamura et al. 1993; Noda et al. 1994). A study in rats that included maternal exposure to tributyltin 

chloride during lactation showed that little, if any, tributyltin or dibutyltin is transferred to the suckling 

pups via the maternal milk (Cooke et al. 2004). A companion paper reported subtle alterations in 

immunological parameters in pups from rats that were exposed during pregnancy during lactation, and 

then the pups were exposed directly until 90 days of age (Tryphonas et al. 2004). As with reproductive 

effects, the role of maternal toxicity in the manifestation of adverse developmental effects is not totally 

clear. The mechanism responsible for the teratogenic activity of organotins is not known and studies 

should continue to investigate the events at the molecular level that may be affected. The use of in vitro 

systems (i.e., cultured rat embryos) may be preferable to studies in the whole animal, as the experimental 

conditions in the former are easier to manipulate than in the latter. Two studies in rats exposed to 

tributyltin chloride suggested that perinatal exposure can affect some developmental landmarks (Ogata et 

al. 2001; Omura et al. 2001). Whether this is a result of endocrine disrupting ability of these compounds 

or from other mechanisms is important to know. Triethyltins and trimethyltins are neurotoxic to humans 

and animals and have been extensively used as tools to investigate the relationship between localized 

lesions within the central nervous system and behavioral alterations. Continued research in this area is 

important to determine susceptible developmental periods during which alterations of neuronal structures 

will cause long-lasting effects or accelerate specific aspects of the normal aging processes. 

Immunotoxicity. There currently is no information available in humans or animals suggesting that 

the immune system is a major target of inorganic tin toxicity, or that the immune system is a target of 

organic tin toxicity in humans. However, there is considerable information on the immunotoxic effects of 

some organotins administered to animals orally or by injection, and from in vitro tests systems. Studies 

have compared various organotins for several animal species (Seinen et al. 1977a, 1977b; Snoeij et al. 

1985). The immunotoxic effect is characterized by reduced thymus weight and size and lymphocyte 

depletion (Krajnc et al. 1984; Seinen and Willems 1976; Seinen et al. 1977a, 1977b; Smialowicz et al. 

1989, 1990; Snoeij et al. 1985). While dialkyltins appear to interfere directly with the proliferation of 

lymphocytes, tributyltin oxide has a direct action on lymphocytes in the thymus (Boyer 1989). The 

results of a study that reported alterations in the humoral immune response in rats exposed orally to 

dibutyltin dichloride were used as basis for derivation of an intermediate-duration oral MRL for dibutyltin 

dichloride (Seinen et al. 1977b). Long-term studies with tributyltin oxide in rats showed alterations in 

parameters of specific and nonspecific resistance (Vos et al. 1990). The results from this study were used 

as the basis for derivation of an intermediate- and a chronic-duration oral MRL for tributyltin oxide. It is 
TIN AND TIN COMPOUNDS 219 

3. HEALTH EFFECTS 

reasonable to assume that similar effects would occur in animals exposed to sufficiently high amounts of 

organotins by the inhalation and dermal routes. Future research should continue to focus on determining 

the basis for interspecies differences including pharmacokinetic differences, and differences at the cellular 

and molecular levels. It would be valuable to determine whether primates exhibit responses similar to 

rodents and if so, whether subtle alterations in immune parameters alter resistance to challenges with 

pathogens. A recent study evaluated immunocompetence in rats exposed during gestation and as 

juveniles and found subtle alterations of unknown toxicological significance (Tryphonas et al. 2004). 

Replication of these findings would be valuable. 

Neurotoxicity. There are no studies in humans regarding neurotoxic effects after inhalation, oral, or 

dermal exposure to inorganic tin compounds. Limited animal data suggest that oral exposures to high 

concentrations of inorganic tins may induce effects on the central nervous system (WHO 1980), but the 

nervous system is not a sensitive target for inorganic tin toxicity. 

Neurotoxic effects have been reported in humans after inhalation (Feldman et al. 1993; Rey et al. 1984; 

Ross et al. 1981; Saary and House 2002; Yanofsky et al. 1991), oral (Foncin and Gruner 1979; Kreyberg 

et al. 1992; Lin et al. 1998; Wu et al. 1990), and dermal (Colosio et al. 1991) exposure to organotins and 

in animals after oral exposure (i.e., Bouldin et al. 1981; Brown et al. 1984; Eto et al. 1971; Graham and 

Gonatas 1973; Magee et al. 1957; Snoeij et al. 1985; Squibb et al. 1980) to these compounds. Among the 

organotins, trimethyltin and triethyltin have been the most widely studied in acute- and intermediateduration oral studies. These organotins are highly toxic and their effects are well characterized and are 

expected to occur across routes of exposure. Trimethyltin induces neuronal necrosis, particularly in the 

hippocampal region, whereas triethyltin produces intramyelinic edema (Chang 1990). Case studies of 

humans acutely exposed (accidentally or intentionally) to high amounts of trimethyltin or triethyltin and 

studies in animals reported morphological changes in the central nervous system as well as behavioral 

changes that may persist for a long time after the poisoning episode. One typical manifestation of 

trimethyltin intoxication in both humans and animals is aggressive behavior. Both trimethyltin and 

triethyltin have become important research tools for the study of brain function, in particular, to examine 

the association between damage to specific brain structures, such as the hippocampus or brain cell groups 

and behavioral alterations. Additional studies using nerve cells in vitro can provide more information on 

possible mechanisms of action of these organotins at the cellular and molecular levels. Also, studies on 

the effects of tin compounds on glial function, both during neurodevelopment and adulthood, would be 

useful. Studies of the potential effects of long-term exposure to low levels of trimethyltin or triethyltin, as 

it may occur near a waste site that contains these substances, may provide valuable information. 
TIN AND TIN COMPOUNDS 220 

3. HEALTH EFFECTS 

Epidemiological and Human Dosimetry Studies. The general population is exposed to 

inorganic tin compounds through consumption of contaminated food, in industrial settings, and 

potentially at hazardous waste sites through contact with contaminated air, water, and soil. Organotin 

compounds are also used in agricultural and other uses with potential exposure of people by different 

routes, although the main route of exposure is also the oral route. Only limited case reports of human 

exposure and no retrospective or prospective epidemiological studies are available. Occupational studies 

of inorganic tin exposure provide information mostly on respiratory effects in workers exposed 

chronically (Cutter et al. 1949; Dundon and Hughes 1950). In contrast, the neurotoxic effects of some 

organotins are well documented in workers and members of the general population exposed by all routes 

(Colosio et al. 1991; Feldman et al. 1993; Kreyberg et al. 1992; Lin et al. 1998; Rey et al. 1984; Ross et 

al. 1981; WHO 1980; Wu et al. 1990; Yanofsky et al. 1991). These cases have generally involved 

accidental or intentional exposure to high amounts of organotins. Should populations with past or 

ongoing exposure to organotins be identified, emphasis should be placed on the evaluation of organs and 

systems that have appeared to be particularly sensitive in animal studies. For example, evaluation of 

immunocompetence should have high priority in people exposed to tributyltin, dibutyltin, or dioctyltin, 

whereas neurobehavioral tests should be conducted in those known to have been exposed or are exposed 

to trimethyltin or triethyltin. 

Biomarkers of Exposure and Effect. 

Exposure. The development of models that would support quantitative estimates of exposure to tin and 

tin compounds based on blood or urine levels of tin, or a specific organotin or metabolite, would be 

valuable. 

Effect. There are no biomarkers of effect specific for tin or tin compounds. Research to identify reliable 

biomarkers for exposure to tin and tin compounds in humans would be useful in order to evaluate the 

prevalence and magnitude of exposure in an at-risk population. 

Absorption, Distribution, Metabolism, and Excretion. The toxicokinetics of tin compounds 

have not been adequately characterized to support the development of predictive PBPK models in humans 

(see Section 3.4). Existing models are based entirely on observations in animals (ICRP 2001). No 

quantitative estimates of absorption of inhaled inorganic or organotin compounds are available, for either 

humans or animals. Two balance studies of dietary exposures to inorganic tin provide estimates of 
TIN AND TIN COMPOUNDS 221 

3. HEALTH EFFECTS 

gastrointestinal absorption in humans that suggest considerable interindividual variability and, possibly, 

dose dependence (Calloway and McMullen 1966; Johnson and Greger 1982). Estimates of gastrointestinal absorption of organotin compounds in humans are not available. Studies in animals suggest that 

redox state (i.e., Sn[II] vs. Sn[IV]) (Hiles 1974) and number of alkyl moieties affect gastrointestinal 

absorption of tin compounds (Bridges et al. 1967; Kimmel et al. 1977; Mushak et al. 1982; Ohhira and 

Matsui 1993a; Ueno et al. 1994) thus, studies in humans that address these potential variables would be 

particularly useful. Information on the distribution of absorbed tin compounds in humans derives from 

analyses of human cadaver tissues (Kehoe et al. 1940; Schroeder et al. 1964). These studies, together 

with studies conducted in animals, suggest that the major sites of deposition of tin in humans appear to be 

similar to those in animals exposed to inorganic tin compounds; however, they provide no information on 

the distribution of specific inorganic or organotin compounds in humans. Quantitative estimates of the 

elimination rates of absorbed tin in humans are not available. Studies in animals indicate that elimination 

rates vary with chemical form and across species, for given tin compounds (Bridges et al. 1967; Brown 

1984; Furchner and Drake 1976; Kimmel et al. 1977; Ueno et al. 1994). 

Available information on the toxicokinetics in animals, while providing abundant information on the 

distribution and elimination kinetics of tin, do not provide adequate information for extrapolation of doses 

from one route of exposure to another (e.g., oral-to-dermal, oral-to-inhalation), for which health effects 

studies are lacking. The major information deficit, in this regard, is insufficient characterization of the 

extents and rates of absorption of tin from major potential routes of exposure (i.e., no information is 

available for the inhalation and dermal routes) and insufficient characterization of the effects of dose on 

gastrointestinal absorption. 

Comparative Toxicokinetics. As noted in Section 3.5.2, information on the toxicokinetics of tin 

compounds in humans is sufficiently limited to preclude comparisons with other species (see Section 3.4). 

Studies in animals are also insufficient for comparisons of the absorption of tin compounds across 

species, from inhalation, oral, or dermal routes (see Section 3.4.1). Several studies have compared rates 

of elimination of tin, administered in various inorganic forms or as organotin compounds, in various 

animal species (Furchner and Drake 1976; Hiles 1974; NTP 1982). These studies demonstrate species 

differences in elimination kinetics that may be germane to extrapolations to humans. For example, the 

elimination kinetics of absorbed inorganic tin occurs more slowly in Rhesus monkeys than in rodents; this 

difference appears to be the result of a larger fraction of the tin body burden associated with the slowest 

kinetic compartment (presumably bone) in monkeys (Furchner and Drake 1976). Organotin compounds, 

in particular methyltin and ethyltin, accumulate in red blood cells to a much greater extent in rats than in 
TIN AND TIN COMPOUNDS 222 

3. HEALTH EFFECTS 

other species, including nonhuman primates (Brown 1984; Rose 1969; Rose and Aldridge 1968). Species 

differences to the hepatotoxic effects of some organotins have been described. Comparative studies with 

tributyltin and dibutyltin in rats, mice and guinea pigs showed the susceptibilities for liver toxicity 

followed the order: mice ! rats ! guinea pigs (Ueno et al. 2003b). Kinetic studies showed that the 

differences in susceptibility appeared to be partly due to differences in metabolism of tributyltin and in 

the distribution of dibutyltin within cell organelles. These observations suggest that a more complete 

characterization of inter-species variability in the toxicokinetics of tin would be useful for extrapolating 

doses across species, in particular, from rats to other species, including humans. 

Information is available to support the development of models of toxicokinetics of various tin compounds 

in rodents and nonhuman primates (e.g., Rhesus monkey, marmoset); however, the current lack of 

observations on the toxicokinetics of tin compounds in humans makes evaluation of such models for 

applications to predicting the toxicokinetics of tin in humans highly uncertain. Useful types of 

observations in humans to support toxicokinetic model development would include: (1) quantifying 

extent and rates of absorption of tin compounds in humans from the inhalation, oral, and dermal 

pathways; (2) quantifying the relative contribution of various excretory routes to elimination of tin 

compounds in humans, including bile, urine, feces, and milk; (3) time course for the concentrations of tin 

in blood and blood plasma (or other tissues) following a single dose or during repeated exposures; 

(4) observing of blood:tissue and/or plasma:tissue concentration ratios for tin; and (5) identifying 

pathways and rates of metabolism of tin compounds. 

Methods for Reducing Toxic Effects. Recommended methods for the mitigation of effects of 

acute exposure to tin compounds include standard treatments and measures to support vital functions 

(HSDB 2003). No information was located concerning mitigation of effects of lower-level or longer-term 

exposure to tin. This, in part, may reflect the fact that no population has been identified as having been 

subjected or currently undergoing exposure to excessive amounts of tin and compounds. Attempts to 

propose studies of specific methods to reduce possible adverse effects do not appear warranted at this 

time. 

Children’s Susceptibility. Data needs relating to both prenatal and childhood exposures, and 

developmental effects expressed either prenatally or during childhood, are discussed in detail in the 

Developmental Toxicity subsection above. 
TIN AND TIN COMPOUNDS 223 

3. HEALTH EFFECTS 

There are no studies that specifically addressed exposure to inorganic tin in children. Workers exposed to 

tin in the air experienced respiratory effects (Cutter et al. 1949; Dundon and Hughes 1950; Pendergrass 

and Pryde 1948) and ingestion of excessive inorganic tin caused gastrointestinal effects (WHO 1980, 

2003). It is reasonable to assume that children exposed in similar manners will experience similar effects. 

Dermal contact with some organotins such as tributyltin can cause skin irritation and exposure by any 

route to trimethyltin or triethyltin can cause serious neurological effects. There is no reason to believe 

that children exposed to these chemicals would exhibit a different response. There is no information on 

whether the developmental process is altered in humans exposed to tin and compounds. Limited evidence 

with tributyltin chloride in rats suggests that this substance may alter developmental events controlled by 

hormones (Ogata et al. 2001; Omura et al. 2001), but further studies are necessary on this issue. The 

possibility that organotin compounds may have endocrine-disrupting ability in mammals has not been 

systematically studied. 

There are no data to evaluate whether pharmacokinetics of tin and tin compounds in children are different 

from adults. There is limited information indicating that inorganic tin can cross the placenta (Theuer et 

al. 1971), and also that dibutyltin can do so and reach the fetus (Nakamura et al. 1993; Noda et al. 1994). 

Administration of dibutyltin and other organotins, such as tributyltin and triphenyltin, to pregnant rodents 

has caused malformations in the fetuses (Ema et al. 1991a, 1991b, 1992, 1995b, 1997b; Faqi et al. 1997; 

Farr et al. 2001; Harazono et al. 1998; Noda et al. 1991a, 1991b), indirectly suggesting that organotins (or 

metabolites) other than dibutyltin also can cross the placenta. There are no studies on whether tin 

compounds can be transferred from mother to offspring through maternal milk. Cross-fostering studies 

can provide important information regarding the role of in utero vs. lactation exposure to tin compounds 

in normal development. There is evidence that acute perinatal exposure to some organotins results in 

altered behavioral responses in rodents tested as adults (i.e., Barone et al. 1995; Reiter et al. 1981; 

Ruppert et al. 1983). Research efforts should continue to focus on the possible underlying mechanisms 

that are responsible for such long-lasting postexposure toxicities. There are no data to permit an 

evaluation of whether metabolism of tin and compounds is different in children than in adults. 

Research into the development of sensitive and specific biomarkers of exposures and effects for tin 

compounds would be valuable for both adults and children. There are no data on the interactions of tin 

with other chemicals in children; however, studies in humans and in animals have shown that dietary tin 

can influence the metabolism of zinc (Greger and Johnson 1981; Johnson and Greger 1982; Rader et al. 

1990), which is essential for normal growth. There are no pediatric-specific methods to reduce peak 

absorption for tin and compounds, to reduce body burdens, or to interfere with the mechanisms of action. 
TIN AND TIN COMPOUNDS 224 

3. HEALTH EFFECTS 

Based on the information available, it is reasonable to assume that the supportive methods recommended 

for maintaining vital functions in adults will also be applicable to children. 

Child health data needs relating to exposure are discussed in Section 6.8.1, Identification of Data Needs: 

Exposures of Children. 

3.12.3 Ongoing Studies 

The following ongoing studies concerning health effects associated with tin and tin compounds were 

identified in the Federal Research in Progress database (FEDRIP 2004). 

Dr. W.D. Atchison, from Michigan State University, East Lansing, Michigan, plans to examine the 

process by which environmental chemicals, such as some organotins, can destroy distinct populations of 

neurons in the brain, especially during development. Specifically, Dr. Atchison will study the effect of 

trimethyltin on the generation of mechanical tension in developing hippocampal pyramidal neurons in 

primary culture, or transformed neuronal cells. This research is sponsored by the National Institute of 

Environmental Health Sciences. 

Dr. M.L. Billingsley, from Penn State University, Hershey, Pennsylvania, plans to use molecular biologic 

approaches to address specific mechanisms that may explain the selective actions of organotin toxicants. 

The first aim will be to investigate the normal function of stannin (a protein isolated from organotinsensitive tissues) and to use targeted gene disruptions to determine the consequences of loss of stannin on 

the elaboration of organotin toxicity. The second aim will use in vivo antisense disruption of stannin 

expression to determine whether this protein is needed for the elaboration of organotin toxicity. This 

research is sponsored by the National Institute of Environmental Health Sciences. 

Dr. A.Z. Mason, from California State University, Long Beach, California, proposes to determine the sublethal model of toxicity of tributyltin (TBT) and assess whether it and other toxicological analogues could 

constitute an environmental hazard to humans. A series of in vivo and in vitro experiments using the 

TBT-sensitive mollusk, Nucella emarginata, and human prostate cancer and hepatoma cell lines have 

been designed to specifically test each of the identified mechanisms of action and determine if TBT acts 

via perturbing aromatase activity, androgen conjugation, and elimination or by potentiation gonadotropin 

neuropeptide release. This research is sponsored by the National Institute of General Medical Sciences. 
TIN AND TIN COMPOUNDS 225 

3. HEALTH EFFECTS 

Dr. K.R. Pennypacker, from the University of South Florida, Tampa, Florida, proposes that brain injury 

leads to activation of NF-kB (nuclear factor kB) in neurons surviving injury and that this activation 

induces the transcription of growth factors that have a decisive role in promoting cell survival. NF-kB 

expression and activity in the rat hippocampus in response to injury caused by excitotoxicity (kainite), 

ischemia (middlecerebral arterial occlusion), and neurotoxicity (trimethyltin) will be examined to 

determine whether activation of NF-kB is a common event in injury to the brain. This research is 

sponsored by the National Institute of Neurological Disorders and Stroke. 

Dr. C.R. Rice, of Mississippi State University, Mississippi State, Mississippi, plans to evaluate the 

immunotoxicity of mixtures of halogenated hydrocarbons (a co-planar PCB) and organotin (TBT) using 

channel catfish and mice as comparative vertebrate models, using the guidelines of the National 

Toxicology Program. Early studies will be devoted to establishing dose-dependent indices of toxicity that 

will be used to monitor the relative immunotoxicity of a co-planar PCB and TBT. Subsequent research 

will be devoted to evaluating the effects of the co-planar PCB and TBT, alone and in combination, on 

innate and antigen-specific immune parameters. This research is sponsored by the Department of 

Agriculture. 

TIN AND TIN COMPOUNDS 227 

4. CHEMICAL AND PHYSICAL INFORMATION 

4.1 CHEMICAL IDENTITY 

Tin is a naturally occurring element that appears in group 14 (4A) of the periodic table at the boundary 

between the metals and nonmetals. Tin can form various compounds, both inorganic and organic. 

Inorganic tin compounds do not contain a tin-carbon bond, whereas organotin compounds contain at least 

one tin-carbon bond (Kroschwitz and Howe-Grant 1997; Lide 2000). The divalent and tetravalent 

oxidation states can be designated using the names stannous and stannic, respectively, in the name of the 

compound. Another commonly encountered nomenclature system, the Stock Oxidation-Number system, 

denotes the oxidation state in Roman numerals in parentheses following the metal’s name: tin(II) and 

tin(IV) (Smith 1996). Table 4-1 lists common synonyms and other pertinent identification information 

for tin and representative inorganic and organic tin compounds. 

4.2 PHYSICAL AND CHEMICAL PROPERTIES 

Tin is a silver-white metal that is malleable and somewhat ductile. It has a highly crystalline structure 

and exists in two allotropic forms at normal pressures. Gray or Į tin exists below 13.2 °C and has a cubic 

structure. At 13.2 °C, gray tin is converted to white or ȕ tin, which has a tetragonal structure. In 

compounds, tin can exist in the +2 or +4 oxidation state. Industrially important organotin compounds 

include the dimethyltin, dibutyltin, tributyltin, dioctyltin, triphenyltin, and tricyclohexyltin families. 

Organotin compounds that are industrially important contain tin in the +4 oxidation state (Kroschwitz and 

Howe-Grant 1997; Lide 2000). Table 4-2 lists important physical and chemical properties of tin and 

representative inorganic and organic tin compounds. 
TIN AND TIN COMPOUNDS 228 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-1. Chemical Identity of Tin and Tin Compoundsa 

Characteristic Tin Tin(II) chloride Tin(IV) oxide 

Synonyms Metallic tin; silver matt Stannous chloride; tin Stannic oxide; tin oxide; 

powder; tin flake dichloride; tin protochloride stannic anhydride 

Trade name No data No data No data 

Chemical formula Sn SnCl2 SnO2 

Chemical structure Sn SnCl2 SnO2 

Identification numbers: 

CAS registry 7440-31-5 7772-99-8 18282-10-5 

NIOSH RTECS XP7320000b XP8700000b XQ4000000b 

EPA hazardous No data No data No data 

waste 

DOT/UN/NA/ IMCO No data No data No data 

shipping 

HSDB 5035 582 5064 

NCI No data C02722 No data 

EINECS 231-141-8 231-868-0 242-159-0 
TIN AND TIN COMPOUNDS 229 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-1. Chemical Identity of Tin and Tin Compoundsa 

Monomethyltin 

Characteristic Tin(II) fluoroborate Tin(II) fluoride trichloride 

Synonyms	 Tetraflurorborate(1-), Stannous fluoride; easygel; Trichloromethyl 

tin(2+) (2:1); tin fluoristan; Gel-Kam; Gel- stannane; methyltin 

bis(tetrafluoroborate) Tin trichloride 

Trade name No data No data No data 

Chemical formula SnB2F8 SnF2 CH3Cl3Sn 

Chemical structure	 Sn(BF4)2 SnF2 Cl 

H3C Sn Cl 

Cl 

Identification numbers: 

CAS registry 13814-97-6 7783-47-3 993-16-8 

NIOSH RTECS No data XQ3450000b WH8585500b 

EPA hazardous No data No data No data 

waste 

DOT/UN/NA/ IMCO No data No data No data 

shipping
 

HSDB No data 783 No data 

NCI No data No data No data 

EINECS 237-487-6 231-999-3 213-608-8
 
TIN AND TIN COMPOUNDS 230 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-1. Chemical Identity of Tin and Tin Compoundsa 

Characteristic Dimethyltin dichloride Trimethyltin chloride 

Monobutyltin 

trichloride 

Synonyms Dichlorodimethyl stannane; 

Cotin 210 

Chlorotrimethyl stannane; 

chlorotrimethyltin; 

trimethylchlorotin 

Mono-n-butyltin 

trichloride; butyltrichloro 

stannane 

Trade name No data No data No data 

Chemical formula C2H6Cl2Sn C3H9ClSn C4H9Cl3Sn 

Chemical structure Cl CH3 Cl 

H3C Sn Cl H3C Sn Cl Sn Cl 

CH3 CH3 

Cl 

Identification numbers: 

CAS registry 753-73-1 1066-45-1 1118-46-3 

NIOSH RTECS WH7245000b WH6850000b WH678000b 

EPA hazardous No data No data No data 

waste 

DOT/UN/NA/ IMCO No data No data No data 

shipping 

HSDB No data 6413 6073 

NCI No data No data No data 

EINECS 212-039-2 213-917-8 214-263-6 
TIN AND TIN COMPOUNDS 231 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-1. Chemical Identity of Tin and Tin Compoundsa 

Characteristic Dibutyltin dichloride Tributyltin chloride Monobutyltin hydride 

Synonyms Dibutyltin chloride; Chlorotributylstannane; tri­ n-Butyltin; 

dichlorodibutyltin; n-butyltin chloride butylstannane; butyltin 

dichlorodibutylstannane trihydride 

Trade name No data No data No data 

Chemical formula C8H18Cl2Sn C12H27ClSn C4H12Sn 

Identification numbers: 

CAS registry 683-18-1 1461-22-9 2406-65-7 

NIOSH RTECS WH7100000b WH6820000b No data 

EPA hazardous No data No data No data 

waste 

DOT/UN/NA/ IMCO No data No data No data 

shipping 

HSDB 6071 No data No data 

NCI No data No data No data 

EINECS 211-670-0 215-958-7 No data 

Chemical structure Cl 

Sn 

Cl 

Sn 

Cl 

Sn 

H 

H 

H 
TIN AND TIN COMPOUNDS 232 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-1. Chemical Identity of Tin and Tin Compoundsa 

Characteristic Monobutyltin ion Dibutyltin hydride Tributyltin hydride 

Synonyms No data	 Di-n-butyltin; Tributylstannane; 

dibutylstannane; dibutyltin tributyltin; Tributylstannic 

dihydride hydride 

Trade name No data No data No data 

Chemical formula C4H8Sn C8H20Sn C12H28Sn 

Chemical structure 3+	 H 

Sn

Sn Sn 

H H 

Identification numbers: 

CAS registry 78763-54-9 1002-53-5 688-73-3 

NIOSH RTECS No data WH6883600b WH8675000b 

EPA hazardous No data No data No data 

waste 

DOT/UN/NA/ IMCO No data No data No data 

shipping
 

HSDB No data No data 6362
 

NCI No data No data No data 

EINECS No data No data 211-704-4
 
TIN AND TIN COMPOUNDS 233 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-1. Chemical Identity of Tin and Tin Compoundsa 

Characteristic Tetrabutyltin Bis(tributyltin) oxide Triethyltin bromide 

Synonyms 

Trade name 

Tetrabutylstannane 

No data 

Lastanox Q; Biomet TBTO; 

oxybis(tributyltin) 

Bromotriethyl-stannane 

TBTOc No data 

Chemical formula C16H36Sn C24H54OSn2 C6H15BrSn 

Chemical structure 

Sn 

Sn O Sn 

Sn Br 

Identification numbers: 

CAS registry 1461-25-2 56-35-9 2767-54-6 

NIOSH RTECS WH8605000b JN8750000b WH6740000b 

EPA hazardous No data No data No data 

waste 

DOT/UN/NA/IMCO No data No data No data 

shipping 

HSDB 6074 6505 No data 

NCI No data No data No data 

EINECS 215-960-8 200-268-0 220-443-5 
TIN AND TIN COMPOUNDS 234 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-1. Chemical Identity of Tin and Tin Compoundsa 

Characteristic Triphenyltin Triphenyltin hydroxide Triphenyltin chloride 

Synonyms Fentin [ISO]; 

triphenylstannylium 

Fentin hydroxide; 

hydroxytriphenyl stannane 

Chlorotriphenyltin; 

triphenylchlorostannane; Aquatin; fentin 

chloride 

Trade name No data No data No data 

Chemical formula C18H15Sn C18H16OSn C18H15ClSn 

Chemical structure 

Sn+ 

Sn OH Sn Cl 

Identification numbers: 

CAS registry 668-34-8 76-87-9 639-58-7 

NIOSH RTECS No data WH8575000b WH6860000b 

EPA hazardous No data No data No data 

waste 

DOT/UN/NA/ IMCO No data No data No data 

shipping 

HSDB No data 1784 6404 

NCI No data C00260 No data 

EINECS No data 200-990-6 211-358-4 
TIN AND TIN COMPOUNDS 235 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-1. Chemical Identity of Tin and Tin Compoundsa 

Mono-n-octyltin 

Characteristic trichloride Di-n-octyltin dichloride Trioctyltin stannane 

Synonyms 

Trade name 

Chemical formula 

Chemical structure 

Identification numbers: 

CAS registry 

NIOSH RTECS 

EPA hazardous 

waste 

DOT/UN/NA/ IMCO 

shipping 

HSDB 

NCI 

EINECS 

Trichlorooctylstannane; 

n-octyltin trichloride 

No data 

C8H17Cl3Sn 

Cl 

Sn Cl 

Cl 

3091-25-6 

WH8590000b 

No data 

No data 

No data 

No data 

221-435-4 

Dichlorodioctyltin; DOTC; 

Stannane, dichlorodioctylNo data 

C16H34Cl2Sn 

Cl 

Sn Cl 

3542-36-7 

WH724700b 

No data 

No data 

No data 

No data 

222-583-2 

No data 

No data 

C24H52Sn 

H 

Sn 

869-59-0 

No data 

No data 

No data 

No data 

No data 

No data 
TIN AND TIN COMPOUNDS 236 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-1. Chemical Identity of Tin and Tin Compoundsa 

Characteristic Tri-n-octyltin chloride Tetra-n-octylstannane 

Synonyms 

Trade name 

Chemical formula 

Chemical structure 

Identification numbers: 

CAS registry 

NIOSH RTECS 

EPA hazardous 

waste 

DOT/UN/NA/ IMCO 

shipping 

HSDB 

NCI 

EINECS 

Chlorotrioctyl-stannane 

No data 

C24H51ClSn 

Cl 

Sn 

2587-76-0 

WH6855000b 

No data 

No data 

No data 

No data 

219-969-8 

Tetraoctylstannane 

No data 

C32H68Sn 

Sn 

3590-84-9 

WH8635500b 

No data 

No data 

No data 

No data 

222-733-7 

a

All information obtained from HSDB 2003 and ChemID 2003, except where noted. 

b

RTECS 2003 

c

Tomlin 1997 

CAS = Chemical Abstracts Service; DOT/UN/NA/IMCO = Department of Transportation/United Nations/North 

America/International Maritime Dangerous Goods Code; EINECS = European Inventory of Existing Chemical 

Substances; EPA = Environmental Protection Agency; HSDB = Hazardous Substances Data Bank; NCI = National 

Cancer Institute; NIOSH = National Institute for Occupational Safety and Health; RTECS = Registry of Toxic Effects 

of Chemical Substances 
TIN AND TIN COMPOUNDS 237 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of Tin and Tin Compoundsa 

Property Tin	 Tin(II) chloride Tin(IV) oxide Tin(II) fluoride 

Molecular weight 118.69 189.60 150.71 156.71 

Color Silver-white White White White 

Physical state Solid Solid Solid Solid 

Melting point 231.9 °C 246 °C 1,630 °C 213 °C 

Boiling point 2,507 °C 623 °C Sublimes 1,800– 850 °C 

1,900 °C 

Density (g/cm3

) 7.265 (white tin) 3.90 6.95 4.57 at 25 °C 

5.769 (gray tin) 

Odor Odorless Odorless No data No data 

Odor threshold: 

Water No data No data No data No data 

Air No data No data No data No data 

Solubility: 

Water Insoluble 90 g/100 g water at Insoluble 30–39% in water at 

20 °C 20 °C 

Other solvents Soluble in Very soluble in Insoluble in alcohol, Practically insoluble 

hydrochloric acid, hydrochloric acid; cold acids; slowly in ethanol, ether, 

sulfuric acid, aqua soluble in alcohol, soluble in hot and chloroform 

regia, alkali, slightly ethyl acetate, concentrated 

soluble in dilute glacial acetic acid, potassium or sodium 

nitric acid sodium hydroxide hydroxide solution 

solution 

Partition coefficients: 

Log octanol/water No data No data No data No data 

Log Koc No data No data No data No data 

Vapor pressure 8x10-3 mm Hg at 25 mm Hg at No data No data 

1,224 °C 427.9 °C 

Henry’s law constant No data No data No data No data 

Autoignition No data No data No data No data 

temperature 

Flashpoint No data No data No data No data 

Flammability limits No data No data No data No data 

Explosive limits No data No data No data No data 
TIN AND TIN COMPOUNDS 238 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of Tin and Tin Compoundsa 

Monomethyltin Dimethyltin Trimethyltin Monobutyltin 

Property trichloride dichloride chloride trichloride 

Molecular weight 240.08b 219.67b 199.26 282.17 

Color Colorlessb Colorlessb Colorless Colorless 

Physical state Solidb Solidb Solid Liquid 

Melting point 43 °Cb 90 °C (107 °C)b 37.5 °C -63 °C 

Boiling point 171 °Cb 185–190 °Cb 154–156 °C 102 °C at 12 mm Hg 

Density (g/cm3

) No data No data No data 1.71 at 25 °C 

Odor No data No data No data No data 

Odor threshold: 

Water No data No data No data No data 

Air No data No data No data No data 

Solubility: 

Water Soluble in cold 

waterb 

Soluble in cold 

waterb 

Miscible with water Sparingly soluble in 

water 

Other solvents Soluble in organic 

solventsb 

Soluble in organic 

solventsb 

Soluble in organic 

solvents 

Soluble in organic 

solvents 

Partition coefficients: 

Log octanol/water 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 constant No data No data No data No data 

Autoignition No data No data No data No data 

temperature 

Flashpoint 105 °F (40 °C)c No data 207 °F (97 °C)c No data 

Flammability limits No data No data No data No data 

Explosive limits No data No data No data No data 
TIN AND TIN COMPOUNDS 239 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of Tin and Tin Compoundsa 

Dibutyltin Bis(tributyltin)
 

Property dichloride oxide Tributyltin chloride Tributyltin hydride 

Molecular weight 303.85 596.11 325.49d 291.09 

Color White Slightly yellow Colorlessd No data 

Physical state Solid Liquid Liquidd Liquid 

Melting point 43 °C <-45 °Ce No data No data 

Boiling point 135 °C at 10mmHg 180°C at 2 mm Hg 145–147 °C at 5 mm 

Hge 

112.5-113.5 °C at 8 

mm Hg 

Density (g/cm3

) 1.36 at 24 °C 1.17 at 25 °C 1.20e 1.103 at 20 °C 

Odor No data Weak odor No data No data 

Odor threshold: 

Water No data No data No data No data 

Air No data No data No data No data 

Solubility: 

Water Insoluble in cold 

water 

4 mg/L at pH 7, 

20 °C 

Insoluble in cold 

waterd 

No data 

Other solvents Soluble in ether Miscible with Soluble in No data 

benzene, alcohol organic solvents oxygenated, 

chlorinated and 

aromatic solventsd 

Partition coefficients: 

Log octanol/water 0.97 No data No data No data 

Log Koc No data No data No data No data 

Vapor pressure 2 mm Hg at 100 °C 7.5x10-6 mm Hg at 

20 °Cf 

No data No data 

Henry’s law constant No data No data No data No data 

Autoignition No data No data No data No data 

temperature 

Flashpoint 335 °F (168 °C) >212 °F (100 °C) >230 °F (110 °C)c 104 °F (40 °C)c 

Flammability limits No data No data No data No data 

Explosive limits No data No data No data No data 
TIN AND TIN COMPOUNDS 240 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of Tin and Tin Compoundsa 

Triethyltin Triphenyltin Triphenyltin 

Property Tetrabutyltin bromide hydroxide chloride 

Molecular weight 347.16 285.79b 367.03 385.48 

Color Colorless or slightly Colorlessb White White 

yellow 

Physical state Oily liquid Liquidb Solid Solid 

Melting point -97 °C -13.5 °Cb 119 °C 103.5 °C 

Boiling point 145 °C at 10 mm 223–224 °Cb No data 240 °C at 

Hg 13.5 mmHg 

Density (g/cm3

) 1.054 at 20 °C 1.630 g/mLb 1.54 at 20 °C No data 

Odor Distinct, No data Odorless No data 

characteristic 

Odor threshold: 

Water No data No data No data No data 

Air No data No data No data No data 

Solubility: 

Water Insoluble in water Very slightly 1.2 mg/L at 20 °C 40 mg/L at 20 °C 

soluble in cold 

waterb 

Other solvents Soluble in organic 

solvents 

Soluble in organic 

solventsb 

Slightly soluble in 

toluene, alcohol 

Moderately soluble 

in organic solvents 

Partition coefficients: 

Log octanol/water No data No data 3.53 4.19 

Log Koc No data No data No data No data 

Vapor pressure No data No data 3.53x10-7 mm Hg at No data 

25 °C 

Henry’s law constant No data No data No data No data 

Autoignition No data No data No data No data 

temperature 

Flashpoint 225 °F (107 °C)c 211 °F (99 °C)c 211 °F (99 °C)c No data 

Flammability limits No data No data No data No data 

Explosive limits No data No data No data No data 
TIN AND TIN COMPOUNDS 241 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of Tin and Tin Compoundsa 

Property Tetraoctylstannane 

Molecular weight 571.59b 

Color No data 

Physical state No data 

Melting point No data 

Boiling point 268 °C at 10 mm Hgb 

Density (g/cm3) 0.9605b 

Odor No data 

Odor threshold: 

Water No data 

Air No data 

Solubility: 

Water No data 

Other solvents No data 

Partition coefficients: 

Log octanol/water No data 

Log Koc No data 

Vapor pressure No data 

Henry’s law constant No data 

Autoignition No data 

temperature 

Flashpoint No data 

Flammability limits No data 

Explosive limits No data 

a

All information obtained from HSDB 2003, except where noted. b

Weast 1980 

c

Aldrich 2003-2004 

d

Ashford 1994 

e

Lewis 1997 

f

Blunden et al. 1984 

TIN AND TIN COMPOUNDS 243 

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

5.1 PRODUCTION 

No information is available in the TRI database on facilities that manufacture or process tin or tin 

compounds because these chemicals are not required to be reported under Section 313 of the Emergency 

Planning and Community Right-to-Know Act (Title III of the Superfund Amendments and 

Reauthorization Act of 1986) (EPA 1997). 

The earth's crust contains about 2–3 ppm tin, comprising 0.0006% of the earth's crust (Budavari 2001; 

Bulten and Meinema 1991). The most important tin containing mineral is cassiterite, SnO2. Other tin 

minerals are stannite, teallite, cylindrite, and canfieldite. After tin-containing ores are mined, they 

undergo further separation processing resulting in concentrates containing 70–77% tin by weight, which 

is almost pure cassiterite, and are ready for smelting (Gaver 1997). 

The world's largest producer of tin in 2003 was Indonesia (33% of the world total), followed by China 

(24%), Peru (19%), Bolivia (7%), Brazil (7%), and Australia (3%). Of the 20 countries that mine tin, 

these six account for 93% of the world total of 2.09x105

 metric tons. Tin has not been mined in the 

United States since 1993. Production of tin stopped in 1989 at the only U.S. tin smelter at Texas City, 

Texas. However, the United States is believed to be the world's largest producer of secondary tin. In 

2003, about 11,000 metric tons of tin from old and new scrap were recycled at 3 detinning plants and 

70 secondary nonferrous-metal processing plants. The Defense Logistics Agency, which manages the 

National Defense Stockpile, sold 8,876 metric tons of pig tin from the stockpile in 2003. The Steel 

Recycling Institute stated that the steel can (tin-plated) recycling rate in the United States in 2003 was 

60%. Tin is recovered, in addition to steel, in can recycling (Carlin 2003b, 2004). Production of 

organotin compounds was 5,000 tons in 1955 and approximately 35,000 tons in 1985 (Fent 1996). More 

recent production numbers for organotin compounds could not be located. Thirty one organotin 

compounds (e.g., bis(tributyltin) oxide, triphenyltin hydroxide, dibutyltin dichloride) are included on the 

U.S. High Production Volume (HPV) chemicals lists for 1990 and 1994. HPV chemicals are those that 

are manufactured in or imported into the United States in quantities one million pounds per year (EPA 

2004). Current U.S. manufacturers of selected tin compounds are given in Table 5-1. 
TIN AND TIN COMPOUNDS 244 

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

Table 5-1. Current U.S. Manufacturers of Selected Tin Compoundsa 

Company Location 

Inorganic tin compounds 

Tin(II) chloride 

ATOFINA Chemicals, Inc. Specialty Chemicals Division Carrollton, Kentucky 

Tin(II) fluoride 

Ozark Fluorine Specialties, Inc. Tulsa, Oklahoma 

Tin(IV) oxide 

Engelhard Corporation, Appearance and Performance - Technologies Elyria, Ohio 

Ferro Corporation, Coatings, Colors, and Ceramics Group - Electronic Penn Yan, New York 

Materials Division 

Tin(II) fluoroborate 

Atotech USA Inc. Rock Hill, South Carolina 

General Chemical Corporation Claymont, Delaware 

OMG Fidelity, Inc. Newark, New Jersey 

Solvay Fluorides Inc. St. Louis, Missouri 

Methyltin compounds 

Dimethyltin dineodecanoate 

Gelest, Inc. Tullytown, Pennsylvania 

Tetramethyltin 

Clariant Life Science Molecules (America) Inc. Gainesville, Florida 

Gelest, Inc. Tullytown, Pennsylvania 

Butyltin compounds 

Dibutyltin acetylacetonate 

MacKenzie Company Bush, Louisiana 

Dibutyltin bis(2,4-pentanedionate) 

Gelest, Inc. Tullytown, Pennsylvania 

Dibutyltin bis(2-ethylhexanoate); Dibutyltin bis(isooctyl) maleate; Dibutyltin 

bis(isooctyl mercaptoacetate); Dibutyltin bis(isopropyl maleate); Dibutyltin 

bis(n-lauryl mercaptide); Dibutyltin dibutoxide; Dibutyltin dimethoxide; 

Dibutyltin disalicylate; Dibutyltin mercaptopropionate; Dibutyltin sulfide; 

Tributyltin fluoride 

ATOFINA Chemicals, Inc. Specialty Chemicals Division Carrollton, Kentucky 

Dibutyltin chloride; Dibutyltin oxide; Bis(tributyltin) oxide 

ATOFINA Chemicals, Inc. Specialty Chemicals Division Axis, Alabama; 

Carrollton, Kentucky 

Dibutyltin diacetate 

ATOFINA Chemicals, Inc. Specialty Chemicals Division Carrollton, Kentucky 

Ferro Corporation Performance and Fine Chemicals Group - Polymer Walton Hills, Ohio 

Additive Division 

Dibutyltin difluoride 

ATOFINA Chemicals, Inc. Specialty Chemicals Division Carrollton, Kentucky 

Atotech USA Inc. Rock Hill, South Carolina 
TIN AND TIN COMPOUNDS 245 

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

Table 5-1. Current U.S. Manufacturers of Selected Tin Compoundsa 

Company Location 

Dibutyltin dilaurate 

ATOFINA Chemicals, Inc. Specialty Chemicals Division Carrollton, Kentucky 

Ferro Corporation Performance and Fine Chemicals Group - Polymer Walton Hills, Ohio 

Additives Division 

Johnson Matthey, Inc. Alfa Aesar Ward Hill, 

Massachusetts 

Dibutyltin maleate 

ATOFINA Chemicals, Inc. Specialty Chemicals Division Carrollton, Kentucky 

Ferro Corporation Performance and Fine Chemicals Group - Polymer Walton Hill, Ohio 

Additive Division 

Tributyltin chloride 

ATOFINA Chemicals, Inc. Specialty Chemicals Division Axis, Alabama; 

Carrollton, Kentucky 

Tributyltin hydride 

Gelest, Inc. Tullytown, Pennsylvania 

Johnson Matthey, Inc. Alfa Aesar Ward Hill, 

Massachusetts 

Sigma-Aldrich Fine Chemicals Plant location not 

specified
 

Tetrabutyltin 

ATOFINA Chemicals, Inc. Specialty Chemicals Division Axis, Alabama 

Octyltin compounds 

Dioctyltin S,S'-bis(isooctylmercaptoacetate); Dioctyltin dichloride; Dioctyltin 

maleate 

ATOFINA Chemicals, Inc. Specialty Chemicals Division Carrollton, Kentucky 

Dioctyltin dilaurate 

ATOFINA Chemicals, Inc. Specialty Chemicals Division Carrollton, Kentucky 

Gelest, Inc. Tullytown, Pennsylvania 

Dioctyltin oxide 

ATOFINA Chemicals, Inc. Specialty Chemicals Division Carrollton, Kentucky; 

Axis, Alabama 

Tetraoctyltin 

ATOFINA Chemicals, Inc. Specialty Chemicals Division Axis, Alabama 

Phenyltin compounds 

Diphenyltin chloride; Diphenyltin oxide; Triphenyltin fluoride 

ATOFINA Chemicals, Inc. Specialty Chemicals Division Carrollton, Kentucky 

a

Derived from SRI 2004. SRI reports production of chemicals produced in commercial quantities (defined as 

exceeding 5,000 pounds or $10,000 in value annually) by the companies listed. 
TIN AND TIN COMPOUNDS 246 

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

5.2 IMPORT/EXPORT 

U.S. consumption of primary and secondary tin was 34,000 and 5,830 metric tons, respectively, in 2002, 

and is estimated as 36,000 and 8,460 metric tons, respectively, for 2003. U.S. imports of refined tin in 

2002 totaled 42,200 metric tons and were mainly from Peru, followed by China, Bolivia, Brazil, and 

Indonesia. Tin imports for 2003 are estimated at 37,000 metric tons. Major imports of tin include 

unwrought metal, waste and scrap, and unwrought tin alloys. Tin exports of refined tin were 2,940 metric 

tons in 2002, and are estimated at 4,020 metric tons for 2003 (Carlin 2004). U.S. imports for 

consumption of dibutyltin oxide, tetrabutyltin, and other organotin compounds were approximately 447, 

611, and 2,070 metric tons, respectively in 2003, and were approximately 266, 649, and 1,680 metric tons, 

respectively, through August 2004 (ITA 2004). 

5.3 USE 

The major uses of tin in 2003 were: cans and containers, 27%; electrical, 23%; construction, 10%; 

transportation, 10%; and others 30% (Carlin 2004). Tinplate is used in food packaging, aerosol 

containers, and decorative applications. Various tin alloys are important, including bronze and pewter. 

Tin readily forms alloys with other metals and imparts hardness and strength. Tin is an important 

component of solders, since it wets the base metal by alloying with it (Gaver 1997). 

Inorganic tin compounds are used in the glass industry, where they are added to strengthen the glass. 

Inorganic tin compounds also serve as the base for the formulation of colors, as catalysts, and in perfumes 

and soaps (WHO 1980). Tin(IV) oxide (SnO2) is used in the ceramics and glass industries, as well as a 

polishing agent and as a catalyst (Kroschwitz and Howe-Grant 1997). It is also used to produce milky or 

colored glass and in the formulation of fingernail polish (Windholz 1983). Tin(IV) chloride (SnCl4) is 

often used as the starting material for the production of organotin compounds. Tin(II) fluoride (SnF2) is 

added to toothpastes as an anticaries agent. Tin(II) chloride (SnCl2) is the most important inorganic tin 

compound. It is used as an industrial reducing agent and in tin electroplating. Tin(II) chloride is also 

used as a food additive, (e.g., as a preservative and a color-retention agent). Tin(II) fluoroborate 

(Sn(BF4)2), which is not isolated as a solid but is only found in solution, is an important chemical in 

electroplating. The consumption of inorganic tin compounds is lower than that of organotin compounds 

(Graf 1996; Kroschwitz and Howe-Grant 1997). 
TIN AND TIN COMPOUNDS 247 

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

Examples of commercially important organotin compounds include tetraorganotins (R4Sn), triorganotins 

(R3SnX), diorganotins (R2SnX2), and monoorganotins (RSnX3). The organotin compounds of 

commercial importance have R groups equal to methyl, butyl, octyl, cyclohexyl, phenyl, or neophyl. The 

anionic X groups are commonly halides, oxide, hydroxide, carboxylates, or mercaptides. Tetraorganotin 

compounds are mainly used in the production of tri-, di-, and monoorganotin compounds. Tri- and 

diorganotin compounds are the most important classes of organotin compounds. Triorganotin compounds 

are used as industrial biocides, agricultural chemicals, wood preservatives, and marine antifouling agents. 

Diorganotin compounds are used as polyvinyl chloride (PVC) stabilizers and as polyurethane foam and 

esterification catalysts. Monoorganotin compounds are also used as PVC stabilizers, as well as in the 

treatment of glass (Batt 2004; Kroschwitz and Howe-Grant 1997). 

The major commercial applications for which organotin compounds are used are as PVC heat stabilizers, 

biocides, catalysts, agrochemicals, and glass coatings, accounting for approximately 20,000 tons of tin 

consumption per year (Batt 2004). The major use of organotin compounds is for heat stabilization of 

PVC, which represents approximately two-thirds of the global consumption (Sadiki and Williams 1999). 

It was estimated that in 1981, the U.S. consumption of organotin compounds as PVC stabilizers was 

10,650 tons, approximately 27% of the world market (Kroschwitz and Howe-Grant 1997). Organotin 

compounds used as PVC stabilizers include butyl-, octyl-, and methyltin compounds. Octyl- and 

methyltin compounds are used in PVC for food packaging. In the United States, the organotin 

compounds that are used predominantly as PVC stabilizers are methyltins (about 50% of the market) and 

butyltins (40%), with octyltin compounds making up the remainder. In Asia, methyltins (50%) and 

octyltins (40%) and in Europe, octyltins (60%) and butyltins (30%) are the most widely used organotin 

compounds as PVC stabilizers (Leaversuch 1999). Tributyltin compounds are also used as slimicides on 

masonry, as disinfectants, and as biocides for cooling systems, power station cooling towers, pulp and 

paper mills, breweries, leather processing, and textile mills (WHO 1990). 

The use of triorganotin compounds as marine antifoulants has been restricted by the Organotin 

Antifouling Paints Control Act (June 16, 1988), which limits the type of vessel on which these paints can 

be used, and limits the use of tributyltin paints to those that have laboratory tested release rates of 

4 μg/cm2

/day (Cardwell et al. 1999a). France was the first country to adopt restrictions in 1982, and 

now the majority of industrialized countries have adopted restrictions on the use of tributyltin containing 

paints on vessels <25 meters in length, and include, in addition to France and the United States, the 

United Kingdom, Canada, New Zealand, Australia, and the European Union (Birchenough et al. 2002). 

On October 5, 2001, the International Maritime Organization (IMO) adopted the International Convention 
TIN AND TIN COMPOUNDS 248 

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

on the Control of Harmful Anti-fouling Systems on Ships, which prohibits the use of harmful organotin 

compounds in anti-fouling paints on ships and established a mechanism to prevent the potential future use 

of other harmful substances as anti-fouling systems (IMO 2004). 

5.4 DISPOSAL 

Tin-containing wastes in the form of salts, slags, and muds are generated as a result of smelting, refining, 

and detinning processes. Solid wastes containing tin are generated by both domestic and industrial users 

of containers. Tin-containing wastes may be incinerated or disposed of in landfills (WHO 1980). 

Inorganic and organic tin compounds may be disposed of in sealed containers in a secured sanitary 

landfill (NIOSH/OSHA 1981). 

Tin is not listed as a hazardous waste constituent by the EPA and therefore, its disposal is not restricted 

by federal land disposal restrictions. No data were located regarding the amounts of tin disposed of by 

any means or trends in the disposal of tin. 
TIN AND TIN COMPOUNDS 249 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.1 OVERVIEW 

Tin and organotin compounds have been identified in at least 214 and 8 sites, respectively, of the 

1,662 hazardous waste sites that have been proposed for inclusion on the EPA National Priorities List 

(NPL) (HazDat 2004). However, the number of sites evaluated for tin and organotin compounds is not 

known. The frequency of these sites can be seen in Figures 6-1 and 6-2, respectively. All sites where tin 

and organotin compounds were found are located in the United States. 

Tin occurs naturally in the earth's crust with a concentration of approximately 2–3 ppm (Budavari 2001). 

Tin compounds are found in various environmental media in both inorganic and organic forms. Tin may 

be released to the environment from natural and anthropogenic sources. Tin is a component of many soils 

and inorganic tin compounds may be released in dusts from wind storms, roads, and agricultural 

activities. Releases of tin to environmental media may occur from the production and use of tin and tin 

compounds. Gases, dusts, and fumes containing tin may be released from smelting and refining 

processes, industrial uses of tin, waste incineration, and burning of fossil fuels (Byrd and Andreae 1986; 

Senesi et al. 1999; WHO 1980). In general, organotin compounds are released to the environment from 

anthropogenic sources; however, methyltin compounds can be produced in the environment by 

biomethylation of inorganic tin and can occur naturally (Fent 1996). Antifouling paints containing 

tributyltin are applied as a finish coat to the immersed sections of boats and floating structures. As the 

paint releases tributyltin into the water, it creates an environment that repels the organisms that may 

attach to the surface of submerged objects. Use of antifouling paints represents the major source of 

tributyltin into the coastal environment (Alzieu 1998). The use of tributyltin compounds as slimicides on 

masonry, disinfectants, and biocides for cooling systems, power station cooling towers, pulp and paper 

mills, breweries, leather processing, and textile mills (WHO 1990) may result in their release to the 

environment. Triphenyltin enters the environment directly from its use as a pesticide. To a lesser extent, 

organotin compounds may also enter the environment by leaching to soil and groundwater from consumer 

products containing organotin compounds disposed of in landfills (Fent 1996). 

Tin may exist in either divalent (Sn2+) or tetravalent (Sn4+) cationic (positively charged) ions at 

environmental conditions. Tin(II) dominates in reduced (oxygen-poor) water, and will readily precipitate 

as a sulfide (SnS) or as a hydroxide (Sn(OH)2) in alkaline water. Tin(IV) readily hydrolyzes, and can 

precipitate as a hydroxide. In general, tin(IV) would be expected to be the only stable ionic species in the 
TIN AND TIN COMPOUNDS 250 

6. POTENTIAL FOR HUMAN EXPOSURE 

Figure 6-1. Frequency of NPL Sites with Tin Contamination 

Frequency of 

NPL Sites 

1-2
 

3-4
 

5-6
 

7-8
 

Derived from HazDat 2005 9-10
 
 

11-19
 
TIN AND TIN COMPOUNDS 251 

6. POTENTIAL FOR HUMAN EXPOSURE 

Figure 6-2. Frequency of NPL Sites with Organotin Contamination 

Frequency of 

NPL Sites 

1 

3 

Derived from HazDat 2005 
TIN AND TIN COMPOUNDS 252 

6. POTENTIAL FOR HUMAN EXPOSURE 

weathering cycle (Wedepohl et al. 1978). Tin in water may partition to soils and sediments. Cations such 

as Sn2+ and Sn4+ will generally be adsorbed by soils to some extent, which reduces their mobility. Tin is 

generally regarded as being relatively immobile in the environment (Gerritse et al. 1982; WHO 1980). 

Organotin compounds are generally only sparingly soluble in water and are likely to partition to soils and 

sediments. Most commercially used organotin compounds are relatively immobile in environmental 

media due to their low vapor pressures, low water solubilities, and high affinities for soil and organic 

sediments (Blunden et al. 1984). For example, nearly all of the tributyltin found in the water column is 

bound to suspended particles, with a small portion associated with dissolved organic matter and organic 

and inorganic ligands (Gadd 2000). Tributyltin that is associated with particles in the water column may 

settle out, which is an important process in its removal from the water column. Tributyltin sorption 

coefficients to sediments can range from 100 to 10,000 (Anderson et al. 2002). Degradation of organotin 

compounds involves breaking the tin-carbon bond and can occur in the environment by ultraviolet (UV) 

irradiation, or biological or chemical cleavage (Blunden et al. 1984). Rates of photodegradation and 

biodegradation of organotins in water are dependent upon environmental conditions. In sediment, 

organotins are generally persistent. Organotin compounds may be significantly bioconcentrated by 

aquatic organisms. Cleavage of the tin-carbon bond by hydrolysis is not a significant environmental fate 

process under environmental conditions (WHO 1990). 

Occupational exposure to tin may be significant in some industrial environments. Ambient environmental levels of tin are generally quite low, except in the vicinity of pollution sources. Humans may be 

exposed to tin by inhalation, ingestion, or dermal absorption. However, typical human exposure to tin is 

primarily by ingestion of food. Tin-lined cans used to package food constitute the most important 

contribution to tin intake in the diet (Biégo et al. 1999). While there is evidence that tin is essential for 

the normal growth of rats, there is no evidence that tin is essential for other animals, including humans 

(WHO 1980). Exposure to organotin compounds may occur by the ingestion of seafood and contact with 

consumer products that contain organotin compounds. Household commodities made up of polyurethane, 

plastic polymers, and silicons contain butyltin concentrations in the parts per million range (Kannan et al. 

1999). Mono- and dimethyltin and mono- and dibutyltin compounds have been detected in drinking 

water in Canada where polyvinyl chloride (PVC) pipes, containing these organotin compounds, are used 

in the distribution of drinking water (Sadiki and Williams 1996, 1999; Sadiki et al. 1996). Organotin 

compounds were detected in household dust in the United Kingdom (Santillo et al. 2003). 
TIN AND TIN COMPOUNDS 253 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.2 RELEASES TO THE ENVIRONMENT 

The Toxics Release Inventory (TRI) data should be used with caution because only certain types of 

facilities are required to report (EPA 1997). Manufacturing and processing facilities are required to report 

information to the TRI only if they employ 10 or more full-time employees; if their facility is classified 

under Standard Industrial Classification (SIC) codes 20–39; and if their facility produces, imports, or 

processes 25,000 pounds of any TRI chemical or otherwise uses >10,000 pounds of a TRI chemical in a 

calendar year (EPA 1997). 

There is no information on releases of tin and tin compounds from manufacturing and processing 

facilities because these releases are not required to be reported (EPA 1997). However, releases of tin to 

environmental media may occur from the production and use of tin and tin compounds. 

Tin and organotin compounds have been identified in a variety of environmental media (air, surface 

water, leachate, groundwater, soil, and sediment) collected at 214 and 8 sites, respectively, of the 

1,662 current or former NPL hazardous waste sites (HazDat 2004). 

6.2.1 Air 

There is no information on releases of tin and tin compounds to the atmosphere from manufacturing and 

processing facilities because these releases are not required to be reported (EPA 1997). 

Tin has been identified in air collected at 6 of the 214 current or former NPL hazardous waste sites where 

it was detected in some environmental media. No organotin compounds were found in air at the eight 

current or former NPL hazardous waste sites where organotin compounds were detected in some 

environmental media (HazDat 2004). 

Tin may be released to the atmosphere from both natural and anthropogenic sources. Tin is a component 

of many soils and may be released in dusts from wind storms, roads, and agricultural activities. Gases, 

dusts, and fumes containing tin may be released from smelting and refining processes, industrial uses of 

tin, waste incineration, and burning of fossil fuels (Byrd and Andreae 1986; Senesi et al. 1999; WHO 

1980). Davison et al. (1974) reported that the tin content of airborne fly ash from coal-burning power 

plants ranged from 7 to 19 μg/g. Worldwide emissions of tin to the atmosphere from coal and oil 

combustion, refuse incineration, and copper/nickel production facilities were estimated at 1,470– 
 

TIN AND TIN COMPOUNDS 254 

6. POTENTIAL FOR HUMAN EXPOSURE 

10,810 metric tons in 1983 (Nriagu and Pacyna 1988). Organotin compounds may be released to air by 

agricultural spraying, volatilization, antifouling paint sprays, incineration of materials treated or stabilized 

with organotin compounds, and glass coating operations. Incineration of organotin containing material is 

unlikely to be a significant source of organotin compounds to air, since these compounds will be 

decomposed to inorganic tin during combustion (Blunden et al. 1984). Releases of organotin compounds 

to air are not significant due to their low vapor pressures and rapid photodegradation (Blunden et al. 1984; 

Fent 1996). 

6.2.2 Water 

There is no information on releases of tin and tin compounds to water from manufacturing and processing 

facilities because these releases are not required to be reported (EPA 1997). 

Tin has been identified in groundwater and surface water at 78 and 36 sites, respectively, of the 214 NPL 

hazardous waste sites where it was detected in some environmental media. Organotin compounds were 

found in surface water at one of the eight current or former NPL hazardous waste sites where they were 

detected in some environmental media; organotin compounds were not found in groundwater at these 

sites (HazDat 2004). 

Releases of tin to water may occur from industrial facilities smelting, refining, or using tin (WHO 1980). 

Antifouling paints containing tributyltin are applied as a finish coat to the immersed sections of boats and 

floating structures. As the paint releases tributyltin into the water, it creates an environment that repels 

the organisms that may attach to the surface of submerged objects. Use of antifouling paints represents 

the major source of tributyltin into the coastal environment. It has been estimated that one boat releases 

1–10 μg tributyltin/cm2

 of hull surface daily to ensure antifouling protection. This corresponds to 0.2– 

2 g/day for a small sailboat and up to 50–500 g/day for an average sized merchant ship (Alzieu 1998). 

The use of triorganotin compounds as marine antifoulants has been restricted by the Organotin 

Antifouling Paints Control Act (June 16, 1988), which limits the type of vessel on which these paints can 

be used, and limits the use of tributyltin paints that have laboratory tested release rates of 4 μg/cm2

/day 

(Cardwell et al. 1999a). Most industrialized countries, in addition to the United States, have adopted 

similar restrictions on the use of tributyltin containing paints. These countries include the United 

Kingdom, Canada, France, New Zealand, Australia, and the European Union (Birchenough et al. 2002). 
TIN AND TIN COMPOUNDS 255 

6. POTENTIAL FOR HUMAN EXPOSURE 

Organotin compounds may also be released to water from overspray and land runoff from agricultural 

applications, industrial processes, and leaching from organotin-stabilized polyvinyl chloride (PVC) 

(Blunden et al. 1984). The use of tributyltin compounds as slimicides on masonry, disinfectants, and 

biocides for cooling systems, power station cooling towers, pulp and paper mills, breweries, leather 

processing, and textile mills may result in their release to the environment (WHO 1990). Triphenyltin 

acetate and triphenyltin hydroxide are used as fungicides, algicides, and molluscicides (WHO 1999). 

Timber treatment facilities can be as a significant source of tributyltin in freshwater systems from 

seepage, accidental spills, and intentional releases. Minor sources of organotin compounds in freshwater 

can be seepage from landfill sites and agricultural runoff, due to the use of contaminated sewage sludge or 

organotin containing pesticides (Demora and Pelletier 1997). Monthly samples of influent, effluent, and 

sludges were collected from July 1990 to January 1991 from sewage treatment plants in five Canadian 

cities. Monobutyltin was detected in all influent samples. Dibutyl- and tributyltin were only detected 

infrequently, and octyltin species were not detected. A significant reduction, 40% on average, in the 

concentration of monomethyltin was found after passage through the sewage treatment plants, due to 

degradation and adsorption to sludge. No butyltin or octyltin species were found in five landfill leachate 

samples in southern Ontario, Canada (Chau et al. 1992). 

6.2.3 Soil 

There is no information on releases of tin and tin compounds to soil from manufacturing and processing 

facilities because these releases are not required to be reported (EPA 1997). 

Tin has been identified in soil at 121 sites and in sediment at 49 sites collected from 214 NPL hazardous 

waste sites, where it was detected in some environmental media. Organotin compounds were found in 

sediment and soil at four sites and one site, respectively, of the eight current or former NPL hazardous 

waste sites where they were detected in some environmental media (HazDat 2004). 

Tin may be released to soil from organotin pesticide usage and landfilling of tin-containing wastes, 

including used cans and organotin-containing plastics (WHO 1980). The application of pre-treated 

municipal sludge and urban refuse as soil amendments may also introduce tin to soils. Concentrations of 

tin in sewage sludges from countries in Europe and North America ranged from 40 to 700 mg/kg dry 

weight. Manures and poultry wastes contained tin at concentrations of 3.7–7.4 and 2.0–4.1 mg/kg dry 

weight, respectively. Other incidental point sources that may introduce tin to soil are corrosion of metal 

objects and dispersion of metallic ores during transport (Senesi et al. 1999). Organotin compounds may 
TIN AND TIN COMPOUNDS 256 

6. POTENTIAL FOR HUMAN EXPOSURE 

be released to soil through agricultural applications and burial of organotin-containing waste material 

(Blunden et al. 1984). An estimated 5,200 tons of organotin compounds were released, primarily to 

landfills in the United States in 1976 (Laughlin and Linden 1985). No current data were found regarding 

releases of organotin compounds to soil. 

6.3 ENVIRONMENTAL FATE 

6.3.1 Transport and Partitioning 

Tin may be transported in the atmosphere by the release of particulate matter derived from the 

combustion of fossil fuels and solid wastes. The vapor pressure of elemental tin is negligible (Cooper and 

Stranks 1966), and inorganic tin compounds are nonvolatile at environmental conditions. Airborne 

particles may travel long distances before deposition depending on the type of emitting source, physical 

form and properties (e.g., size, density), physical or chemical changes that may occur during transport, 

adsorption processes, and meteorological conditions (Senesi et al. 1999). 

Tin may exist in either divalent (Sn2+) or tetravalent (Sn4+) cationic (positively charged) ions at 

environmental conditions. Tin(II) dominates in reduced (oxygen-poor) water, and will readily precipitate 

as a sulfide (SnS) or as a hydroxide (Sn(OH)2) in alkaline water. Tin(IV) readily hydrolyzes, and can 

precipitate as a hydroxide. The solubility product of Sn(OH)4 has been measured at approximately 

10-56 g/L at 25 °C. In general, tin(IV) would be expected to be the only stable ionic species in the 

weathering cycle (Wedepohl et al. 1978). 

Tin in water may partition to soils and sediments. Cations such as Sn2+ and Sn4+ will generally be 

adsorbed by soils to some extent, which reduces their mobility. Tin is generally regarded as being 

relatively immobile in the environment (Gerritse et al. 1982; WHO 1980). However, tin may be 

transported in water if it partitions to suspended sediments (Cooney 1988), but the significance of this 

mechanism has not been studied in detail. Transfer coefficients for tin in a soil-plant system were 

reported to be 0.01–0.1 (Senesi et al. 1999). 

A bioconcentration factor (BCF) relates the concentration of a chemical in plants and animals to the 

concentration of the chemical in the medium in which they live. It was estimated that the BCFs of 

inorganic tin were 100, 1,000, and 3,000 for marine and freshwater plants, invertebrates, and fish, 

respectively (Thompson et al. 1972). Marine algae can bioconcentrate tin(IV) ion by a factor of 

1,900 (Seidel et al. 1980). 
 

TIN AND TIN COMPOUNDS 257 

6. POTENTIAL FOR HUMAN EXPOSURE 

Approximately 95% of tributyltin in the water column was found to be bound to suspended particles and 

the remainder was associated with dissolved organic matter and organic and inorganic ligands (Gadd 

2000). Tributyltin that is associated with particles in the water column may settle out, which is an 

important process in the removal of tributyltin from the water column. Tributyltin sorption coefficients to 

sediments can range from 100 to 10,000 (Anderson et al. 2002). A partition coefficient of about 2,180 at 

20 °C was calculated by Maguire et al. (1985) to estimate the adsorption of tributyltin ions by lake 

sediments. These investigations also concluded that the half-life of the desorption reaction was about 

10 months, indicating that tributyltin can be strongly retained by sediments. The adsorption behavior of 

Sn4+ ion and eight organotin species (tri-, di-, and monobutyltin; tri-, di-, and monomethyltin; and tri- and 

diphenyltin) were studied in a water-sediment system using artificial seawater and estuarine sediment. 

Adsorption coefficients varied from 100.5 to 104.5 and showed the trend of Sn4+ > mono > di > tri in the 

same substituent series. Larger absorption coefficients were found for aromatic compounds than for 

aliphatic compounds (Sun et al. 1996). Sediment-water partition coefficients for tributyltin ranged from 

240 to 65,000 in sediments of the coast of southwestern Spain. Similar values were found for 

monobutyltin. Dibutyltin was found to have higher affinity for sediment (Gomez-Ariza et al. 2001). 

At ambient temperatures, the solubilities of organotin compounds range from 0.0001 to about 50 mg/L 

(Laughlin and Linden 1985; WHO 1980). Organotin compounds may partition from water to aquatic 

organisms. An octanol/water partition coefficient (Kow) describes the partitioning of an organic chemical 

between octanol and water. Octanol is believed to best imitate the fatty structures in plant and animal 

tissues (Kenaga and Goring 1980). The Kow of tributyltin at pH 6 was reported to be about 1,585 by 

Maguire et al. (1983). The most accurate Kow for tributyltin in seawater was 5,500 (Laughlin and Linden 

1985). 

There is no evidence of biomagnification of tributyltin in marine ecosystems, but accumulation may 

occur, resulting in high tissue concentrations in some organisms (Meador 2000). Rüdel (2003) reported 

that, based on a review of the literature, the bioavailability of organotin compounds via the food chain 

appears to be of minor importance for tributyltin and triphenyltin when compared to uptake via the water 

phase. Measured BCF values for bis(tributyltin)oxide with marine oysters were found to range from 

2,300 to 11,400 (Waldock and Thain 1983). A BCF of 30,000 was estimated by Maguire et al. (1984) for 

the bioconcentration of tributyltin cation by freshwater green algae. Seven-day BCF values were derived 

for dibutyltin dichloride, dibutyltin dilaurate, tributyltin chloride, bis(tributyltin) oxide, and triphenyltin 

chloride for muscle, liver, kidney, and vertebra tissue of round crucian carp. The BCF values ranged 
TIN AND TIN COMPOUNDS 258 

6. POTENTIAL FOR HUMAN EXPOSURE 

from 12 in muscle to 5,012 in liver. For all organotin compounds, liver had the highest BCF values. The 

highest BCFs were found for the tributyltin compounds (Tsuda et al. 1986). BCF values for 

bis(tributyltin) oxide for red sea bream (Pagrus major), mullet (Mugil cephalus), and filefish (Rudarius 

erodes) were 9,400–11,000, 2,400–3,000, and 3,200–3,600, respectively, determined in an 8-week flowthrough aquarium system. Larger BCF values were obtained when fish were reared in seawater 

containing lower concentrations of tributyltin. BCF values for triphenyltin chloride for P. major and 

R. erodes were 3,100–3,300 and 4,100, respectively, and were independent of the concentration of 

triphenyltin in the rearing water (Yamada and Takayanagi 1992). The log BCFs for tributyltin in fish 

from the Port of Osaka and the Yodo River, Japan were 3.6–4.2 and 2.9–3.5, respectively (Harino et al. 

2000). After 50 days of exposure to water containing a constant concentration of tributyltin (500 ng/L), 

whole body concentrations in tilapia did not reach a plateau, and the 50-day BCF was 12,300. 

Enrichment of tributyltin was highest in the viscera, followed by gill, and then muscle (Hongxia et al. 

1998). A BCF of 10,500 was found for tributyltin uptake from seawater in marine mussels (Mugil 

graynus) during the 56-day accumulation phase (Suzuki et al. 1998). BCFs were 17,000–350,000, 2,000– 

70,000, and 1,000–70,000 for tri-, di-, and monobutylin, respectively, in mollusks living in southwest 

Spain, showing a decrease in BCF with decreasing lipophilicity for the butyltin compounds (GomezAriza et al. 2001). 

Bioconcentration as a function of pH was studied for triphenyltin and tributyltin in a freshwater sediment 

organism, Chironomus ripaius. At pH 5 and 8, respectively, the BCFs were 310 and 170 for tributyltin, 

and 680 and 510 for triphenyltin. While the difference in BCF at the two pHs was statistically significant 

for tributyltin, it was not for triphenyltin. This may be explained by the speciation differences for each of 

these compounds as pH varies. The acid dissociation constant (pKa) of tributyltin is 6.25, and at pH 5, the 

fraction of tributyltin hydroxide is approximately 5%, with the tributyltin cation as the predominant 

species in solution. The pKa for triphenyltin is 5.2, and at pH 5, approximately 40% is present as 

triphenyltin hydroxide with the remainder as triphenyltin cation. The differences in the observed pH 

dependence between triphenyltin and tributyltin may indicate that the neutral hydroxide species is the 

predominant form taken up by the organism. BCF values of 1,500 and 1,200 at pH 5 and 8, respectively, 

were determined for tetrabutyltin ion, which cannot undergo ionization and was used as a control 

compound. The difference between these BCF values for tetrabutyltin at pH 5 and 8 was not statistically 

significant (Looser et al. 1998). 

Releases of organotin compounds to air from various surfaces are, in general, not significant due to their 

low vapor pressures and rapid photodegradation at surfaces (Fent 1996). It has been reported that 
TIN AND TIN COMPOUNDS 259 

6. POTENTIAL FOR HUMAN EXPOSURE 

methylation of inorganic and organotin compounds, such as di- and tributyltin, are likely to occur in 

sediments, producing potentially volatile organotin compounds. This process may lead to mobilization of 

tin species into the water column and possibly into the atmosphere. However, there is currently no 

significant evidence of losses of organotin compounds to the atmosphere (Amouroux et al. 2000). There 

was no indication that tributyltin in water partitioned to the air during a 62-day period, whereas 20% of 

the water evaporated (Maguire et al. 1983). 

6.3.2 Transformation and Degradation 

6.3.2.1 Air 

No information was located on the transformation or degradation of tin compounds in the atmosphere. 

6.3.2.2 Water 

Inorganic tin cannot be degraded in the environment, but may undergo oxidation-reduction, ligand 

exchange, and precipitation reactions (HSDB 2003). It has been established that inorganic tin can be 

transformed into organometallic forms by microbial methylation (Hallas et al. 1982). Inorganic tin may 

also be converted to stannane (H4Sn) in extremely anaerobic (oxygen-poor) conditions by macroalgae 

(Donard and Weber 1988). 

The speciation of organotin compounds is pH-dependent. At lower pHs, the cationic form will be the 

primary form, and as the pH is increased, the neutral hydroxide compounds will be the predominant 

species. In the environmentally relevant pH range (pH 5–9), the predominant organotin species will be 

the neutral hydroxide compounds (i.e., R3SnOH, R2Sn(OH)2, and RSn(OH)3). High concentrations of 

chloride favor the formation of chloro species. The pKa values for trimethyltin, triethyltin, tributyltin, and 

triphenyltin cations are approximately 6.60, 6.81, 6.25, and 5.2, respectively (Blunden et al. 1984; Fent 

1996; Meador 2000). 

Degradation of organotin compounds involves the breaking of the tin-carbon bond, which may occur by 

UV irradiation, or by biological or chemical cleavage (Blunden et al. 1984). In water, tributyltin can be 

degraded by photochemical and biological processes relatively rapidly; however, adsorption onto 

suspended particulate material in water followed by sedimentation is a key removal process (De Mora and 

Pelletier 1997). The half-life of tributyltin in seawater varies, depending on pH, temperature, turbidity, 
TIN AND TIN COMPOUNDS 260 

6. POTENTIAL FOR HUMAN EXPOSURE 

and light; it is generally estimated to be in the range of 1 day to a few weeks (Alzieu 1998). 

Biodegradation is the major process in seawaters rich in suspended solids, but photolysis, in surface 

waters, exceeds biodegradation in clean seawater. Calculated half-lives range from 6 days in summertime waters rich in suspended particles to 127 days in clean winter waters (Watanabe et al. 1992). 

Tributyltin can be degraded by microbial, microalgal, and fungal populations, as well as by some higher 

organisms, such as fish (Anderson et al. 2002). Cleavage of the tin-carbon bond by hydrolysis is not an 

important fate process under environmental conditions (WHO 1990). 

6.3.2.3 Sediment and Soil 

Inorganic tin cannot be degraded in the environment, but may undergo oxidation-reduction, ligand 

exchange, and precipitation reactions (HSDB 2003). Degradation of organotin compounds in sediments 

is much slower than in water, and half-lives have been estimated to be several years (Alzieu 1998). In 

addition to dealkylation of organotin compounds, methylation of tin and organotin compounds by 

chemical and/or biological means may occur. The contribution of methylation by biotic and abiotic 

mechanisms is not clear. This pathway may result in fully substituted and volatile tin compounds. 

Methylated butyltin compounds, such as tributylmethyltin and dibutyldimethyltin, have been found in 

contaminated harbor sediments and in surface waters (Amouroux et al. 2000; Cooney 1988). Methylation 

of tin in sediments was found to be positively correlated with increasing organic content in sediment and 

to follow predominately a biotic pathway (Hadjispyrou et al. 1998). 

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT 

Reliable evaluation of the potential for human exposure to tin and tin compounds depends in part on the 

reliability of supporting analytical data from environmental samples and biological specimens. 

Concentrations of tin and tin compounds in unpolluted atmospheres and in pristine surface waters are 

often so low as to be near the limits of current analytical methods. In reviewing data on tin and tin 

compounds levels monitored or estimated in the environment, it should also be noted that the amount of 

chemical identified analytically is not necessarily equivalent to the amount that is bioavailable. The 

analytical methods available for monitoring tin and tin compounds in a variety of environmental media 

are detailed in Chapter 7. 

Environmental monitoring studies may report concentrations of organotin compounds in various 

environmental media in two formats, either as mass of tin per unit mass or volume of media, or as mass of 
TIN AND TIN COMPOUNDS 261 

6. POTENTIAL FOR HUMAN EXPOSURE 

organotin ion per unit mass or volume of media. To convert mass on a tin basis to mass on an organotin 

cation basis, multiply by the ratio of the formula weight of the organotin cation to the atomic weight of 

tin. Conversions are provided in Table 6-1 for various organotin cations. For example, a tributyltin 

(TBT) concentration in sediment reported as 122 ng TBT/g would correspond to 50 ng Sn/g, since 

tributyltin ion has a mass that is 2.44 times greater than that of tin. 

6.4.1 Air 

Tin is detected in air infrequently and at low concentrations, except in the vicinity of industrial sources. 

Air concentrations in U.S. cities ranged from below the detection limit to 0.8 μg/m3

 in several studies. 

Average concentrations are generally <0.1 μg/m3

, with higher concentrations near some industrial 

facilities (EPA 1982a; WHO 1980). In some studies, tin was not detected in 40–>50% of samples. 

Atmospheric tin is associated with particulate matter, and peak concentrations were found on smaller 

respirable particles (1–3 μm) (WHO 1980). Samples of airborne inhalable particulate matter were 

collected in two urban/industrial areas in Illinois, southeast Chicago and East St. Louis, over a 2-year 

period. Average tin concentrations in the fine (<2.5 μm) and coarse (2.5–10 μm) particulate fractions 

were <0.007 and 0.012 μg /m3

 for East St. Louis, respectively, and <0.007 μg /m3 for both the fine and 

course fractions in samples from southeast Chicago and a rural site in Bondville, Illinois (Sweet and 

Vermette 1993). The average tin concentration in highway tunnel exhaust aerosol in the Elbtunnel in 

Hamburg, Germany between August 1988 and January 1989 was 10.9 μg/m3

 (Dannecker et al. 1990). 

Tin concentrations in the particulate matter in the ambient air at art glass manufacturing plants measured 

by personal samples from oven-charger and batch-mixer workers ranged from 0.1 to 3.5 μg/m3

 from three 

plants that use arsenic as a fining agent (a fining agent is added to disperse air bubbles in glass). Tin was 

not detected in the particulate matter in the air at three other plants that use antimony compounds instead 

of arsenic (Apostoli et al. 1998). No monitoring data for concentrations of organotin compounds in air 

were found. 

6.4.2 Water 

Tin occurs in trace amounts in natural waters. However, it is seldom measured and only infrequently 

detected, since concentrations are often below the detection limit (NAS 1977; WHO 1980). In surface 

waters, tin was detected in only 3 of 59 samples from 15 U.S. and Canadian rivers at concentrations 

ranging from 1.3 to 2.1 μg/L, and not detected in 119 samples from 28 U.S. rivers. A mean tin 

concentration of 0.038 μg/L was reported for surface water in Maine (NAS 1977; WHO 1980). Tin 
TIN AND TIN COMPOUNDS 262 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-1. Conversion Between Mass on a Tin Basis to 

Mass on an Organotin Cation Basis 

To convert from mass on a tin To: Multiple by: 

basis: 

mass on a TBT cation 2.44 

basis 

mass on a DBT cation 1.96 

basis 

mass on a MBT cation 1.48 

basis 

mass on a TMT cation 1.38 

basis 

mass on a DMT cation 1.25 

basis 

mass on a MMT cation 1.13 

basis 

mass on a TPT cation 2.95 

basis 

mass on a DPT cation 2.30 

basis 

mass on a MPT cation 1.65 

basis 

DBT = dibutyltin; DMT = dimethyltin; DPT = diphenyltin; MBT = monobutyltin; MMT = monomethyltin; 

MPT = monophenyltin TBT = tributyltin; TMT = trimethyltin; TPT = triphenyltin 
TIN AND TIN COMPOUNDS 263 

6. POTENTIAL FOR HUMAN EXPOSURE 

concentrations in public water supplies ranged from 1.1 to 2.2 μg/L in 42 U.S. cities and from 0.8 to 

30 μg/L in 32 of 175 water supplies in Arizona (NAS 1977; WHO 1980). Tin concentrations in drinking 

water have been reported at <10 μg/L (WHO 2003). Tin is present in seawater at about 0.2–3 μg/L (NAS 

1977; WHO 1980). Tin concentration in fresh snow from the French Alps collected in 1998 at different 

altitudes ranged from 157 to 436 pg/g (Veysseyre et al. 2001). 

Concentrations of tributyltin (TBT) were found to range from 20 to 1,800 ng TBT/L in the Chesapeake 

Bay area, Maryland (Hall 1988). In surface waters from San Diego Bay, California in 1986–1989, 

tributyltin levels averaged 4.7–13 ng TBT/L in the north bay, 1.3–9.9 ng TBT/L in the south bay, 3.5– 

14 ng TBT/L in U.S. Navy pier regions, and 19–120 ng TBT/L in yacht harbors. Tributyltin 

concentrations in bottom waters in the San Diego Bay area ranged from 8.8 to 61 ng TBT/L. The mean 

tributyltin concentrations in regional surface waters from Pearl Harbor, Hawaii from 1986 to 1989 were: 

0.0–6.8 ng TBT/L in channels; 0.0–4.9 ng TBT/L in outlying regions; 2.4–31 ng TBT/L in Southeast 

Loch; and 6.7–130 ng TBT/L in a small marina. Tributyltin concentrations in bottom waters in Pearl 

Harbor ranged from 0.0 to 9.7 ng TBT/L. In Honolulu harbor, surface and bottom water tributyltin 

concentrations were 4.8–580 and 2.6–170 ng TBT/L, respectively (Grovhoug et al. 1996). Tributyltin 

concentrations in surface water from the harbor area of Osaka City, Japan ranged from 2 to 33 ng TBT/L 

(Harino et al. 1998). Butyltin compounds were detected in 32 of the 63 seawater samples (0.5 m depth) 

that were collected from 18 areas along the Japanese coast from 1997 to 1999. Average butyltin 

concentrations were 4.6 ng MBT/L, 4.5 ng DBT/L, and 6.8 ng TBT/L from sampling stations for each of 

the four areas: the Pacific coast of northern Japan, the coast along the Sea of Japan, Tokyo Bay and the 

adjacent area, and western Japan. The highest concentrations in these four areas were found in western 

Japan with concentrations of 5.9 ng MBT/L, 6.9 ng DBT/L, and 20.1 ng TBT/L (Takeuchi et al. 2004). 

The seasonal variations in tributyltin concentrations in marinas on Lake Ontario were studied from April 

to December 1998. The marinas were at Toronto, Mississauga, Oakville, Hamilton, and Fifty Point, 

Canada. Approximately 150–200 pleasure boats were in each marina in the summer. Tributyltin 

concentrations increased with increased boat activity, with a maximum concentration of 14 ng Sn/L 

reported in late August at Fifty Point. Concentrations of tributyltin varied at the marinas, peaking 

between June and September, but were always higher in the marinas compared to a reference site, 

Burlington, Canada, that was far from any marinas (Yang and Maguire 2000). Similar seasonal variations 

were seen in seawater collected from marinas and harbors from southwestern Spain. Tri-, di-, and 

monobutyltin concentrations were significantly higher in water collected in May and August compared to 

water collected in November and February. The highest concentrations were found in waters in enclosed 
 

TIN AND TIN COMPOUNDS 264 

6. POTENTIAL FOR HUMAN EXPOSURE 

areas with poor water turnover. Tributyltin concentrations ranged from <0.5 to 31 ng Sn/L. Analysis for 

phenyltin compounds was performed, but none were found (Gomez-Ariza et al. 2001). 

While many studies reported on the occurrence of organotin compounds in marine environments fewer 

studies reported the occurrence of organotin compounds in freshwater. A study investigating the levels of 

di- and tributyltin in fresh surface waters from nine sites across the United States found that, at most sites, 

di- and tributyltin were not detected (detection limits were 970 and 180 ng butyltin ion/L for dibutyltin 

and tributyltin, respectively). The highest dibutyltin concentrations were found in water sampled in 1998 

from the Neuse River, North Carolina and Contentnea Creek, North Carolina at 140 and 160 ng DBT/L, 

respectively. Tributyltin was only detected in the Little Missouri River, North Dakota and Flat River, 

North Carolina at concentrations of 265 and 600 ng TBT/L, respectively (Jones-Lepp et al. 2004). 

Bancon-Montigny et al. (2004) reported a monitoring study involving sampling along 11 rivers in 

southwest France from February to October 2001. Sites were chosen to represent specific industrial or 

agricultural activities. Organotin compounds were detected in most water samples; butyltin compounds 

were most frequently detected with concentrations generally ranging from below the detection limit 

(0.2 ng Sn/L) to 30 ng Sn/L. Phenyltin compounds were also detected at concentrations generally ranging 

from below the detection limit (0.2 ng Sn/L) to 20 ng Sn/L. High phenyltin concentrations were detected 

during the spring and the end of the summer and likely are derived from agricultural sources. 

Monophenyltin concentrations from over 400 up to 700 ng Sn/L were detected at four sampling sites. 

Octyltin compounds were detected as well; however, concentrations were generally lower, ranging from 

below the detection limit (0.2 ng Sn/L) to 15 ng Sn/L (Bancon-Montigny et al. 2004). 

Mono- and dimethyltin and mono- and dibutyltin compounds have been detected in Canadian drinking 

water. Drinking water in Canada is distributed through PVC pipes stabilized with methyl- and butyltin 

compounds. Methyl- and butyltin compounds were detected at concentrations up to 22 and 43.6 ng Sn/L, 

respectively, in distributed water samples from six municipalities in Canada (Sadiki and Williams 1996). 

Tap water in 10 of 22 homes collected in February 1995 from five Canadian municipalities contained 

monomethyltin and dimethyltin compounds at concentrations of 0.5–257 and 0.5–6.5 ng Sn/L, 

respectively. No organotin compounds were detected in the tap water from the other 12 houses. No 

organotin compounds were detected in raw water or in water just after leaving the treatment plant, 

suggesting that the source of these organotin compounds was from some component of the distribution 

system (Sadiki et al. 1996). Canadian drinking water samples collected during the winter–spring 1996 

from 28 sites and autumn 1996 from 21 sites were found to contain monomethyltin, dimethyltin, 

monobutyltin, and dibutyltin in ranges of <0.5–290.6, <0.5–49.1, <0.5–28.5, and <0.5–52.3 ng Sn/L, 
 

TIN AND TIN COMPOUNDS 265 

6. POTENTIAL FOR HUMAN EXPOSURE 

respectively. These compounds were detected with a frequency of 84, 80, 16, and 12% in the winter– 

spring survey and 100, 57, 7, and 7% in the autumn survey, respectively. A summer 1996 survey of 

locations with the highest organotin concentrations in the winter–spring survey showed a decrease in 

mono- and dimethyltin concentration in 89% of the samples. This finding was consistent with laboratory 

studies that showed organotin release from PVC into water decreases after a few days. PVC pipe/tubing 

contains organotin compounds consistent with the organotin patterns found in the distributed water 

samples. Octyltin compounds, which are not used as stabilizers in the PVC used to distribute drinking 

water, were not detected in drinking water samples. Octyltin compounds are used instead as heat 

stabilizers in PVC for food packaging. Except for one treated water sample, no organotin compounds 

were detected in raw or treated water collected at the water treatment plant or in distributed water 

supplied through polyethylene pipes (Sadiki and Williams 1999). 

Organotin compounds were measured in precipitation and fog in the forested catchment in Northeast 

Bavaria, Germany during 2001–2002. Mono-, di-, and tri methyl and butyl derivatives, as well as monoand dioctyltin compounds were detected in precipitation samples collected in this study. The median total 

organotin concentrations in bulk precipitation, throughfall, and fog were 5.83, 14.6, and 57.1 ng Sn/L, 

respectively, over the year-long monitoring study. Monoalkyl tin compounds were the dominant species 

found in precipitation, with concentrations up to 192 ng Sn/L for monobutyltin in fog (Huang et al. 2004). 

6.4.3 Sediment and Soil 

Tin concentrations in soil are generally low, except in areas where tin containing minerals are present 

(Bulten and Meinema 1991). Tin concentrations in the earth's crust are approximately 2–3 mg/kg 

(Budavari 2001). Tin concentrations in soil can range from 2 to 200 mg/kg, but in areas of high tin 

deposits, levels of 1,000 mg/kg may occur (Schafer and Fembert 1984; WHO 1980). The mean 

background soil concentration in the United States is 0.89 mg/kg (Eckel and Langley 1988). Tin 

concentrations in topsoil (0–7.6 cm) from the western end of East St. Louis, Illinois ranged from <13 to 

1,130 mg/kg. East St. Louis has a history of industrial facilities including smelters of ferrous and 

nonferrous metals, a coal-fired power plant, chemical producing companies, and petroleum refineries 

(Kaminski and Landsberger 2000a). Sediment cores collected in January 1996 from Central Park Lake in 

New York City, New York contained average tin concentrations ranging from 4.0 mg/kg at 44–47 cm 

depth to 67 mg/kg at 22–24 cm depth. The average tin concentration in surface sediments (0–2 cm depth) 

in Central Park Lake was 32 mg/kg. The similarities between the history of municipal solid waste 

incineration in New York City and the accumulation of trace metals in the Central Park Lake sediments 
TIN AND TIN COMPOUNDS 266 

6. POTENTIAL FOR HUMAN EXPOSURE 

appear to be consistent with incineration being the major source of several metals to the New York City 

atmosphere (Chillrud et al. 1999). Tin concentrations in sediments from the Wah Chang Ditch and the 

northeast corner of Swan Lake, an area that received runoff from a Texas tin smelter during the 1940s and 

1950s, were found to be as high as 8,000 mg/kg (Park and Presley 1997). 

Organotin concentrations in sediment are summarized in Table 6-2. While tributyltin concentrations in 

water have declined since restrictions on tributyltin use in paints have been in place, concentrations of 

tributyltin in sediments have remained relatively high. Degradation of tributyltin in sediment is much 

slower than in the water column. Recent surveys of tributyltin concentrations in harbors and marinas in 

various countries show concentrations ranging from hundreds of parts per billion (μg/kg) to low parts per 

million (mg/kg) (Meador 2000). Tributyltin concentrations in sediment samples from the harbor area of 

Osaka City, Japan ranged from 0.002 to 0.966 mg TBT/kg dry weight (Harino et al. 1998). Sediment in 

southwestern Spain during November 1993–February 1994 and May–August 1994 were analyzed for the 

presence of butyl- and phenyltin compounds. No phenyltin species were found in sediment, but mono-, 

di-, and tributyltin were found at all stations sampled, with concentrations of tributyltin ranging from 

<0.0006 to 0.16 mg Sn/kg dry weight. Increased concentrations of organotin concentration during 

summer months were not observed in the sediment, as they were in water and biota, and may be due to 

vertical mixing of the sediment layers by natural and boating activities (Gomez-Ariza et al. 2001). Tri-, 

di-, and monobutyltin were detected in superficial sediment samples from five river estuaries (Deba, 

Urola, Oria, Oiartzun, and Bidasoa) of Gipuzkoa, North Spain at concentrations of 0.05–5.48, 0.15–0.71, 

and 0.86–2.87 mg Sn/kg dry weight, respectively. Except for one sampling point, monobutyltin, a 

degradation product of tributyltin, accounted for the largest percentage of total butyltin (>47%) 

(Arambarri et al. 2003). Sediments collected in November 1997 from three sites near Nuuk, Greenland 

contained tributyltin concentrations ranging from <0.001 to 0.171 mg Sn/kg dry weight (Jacobsen and 

Asmund 2000). Tributyltin concentrations were measured in sediment collected in 1997 and 1999 from 

transects along and perpendicular to the shipping lanes in the Sound (Øresund) and the 

Kattegat/Skagerrak region, an important shipping strait between Denmark and Sweden. Tributyltin 

concentrations ranged from 0.0015 to 0.0188 mg TBT/kg dry weight in the Sound and were below the 

detection limit (<0.001 mg TBT/kg dry weight) in the Kattegat region. A strong correlation was observed 

between tributyltin concentration and the organic fraction in sediment samples from the Sound (Strand et 

al. 2003). 

Bancon-Montigny et al. (2004) reported a monitoring study involving sampling along 11 rivers in 

southwest France from February to October 2001. Sites were chosen to represent specific industrial or 
TIN AND TIN COMPOUNDS 267 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-2. Organotin Levels in Sediment 

Nature/location of Concentration of organotin Reported 

sediment compound Units as Reference 

Central-west Greenland, near Nuuk Harbor, surface sediment 

TBT DBT MBT mg Sn/kg dw Mean 

Sandkaj 0.0097 0.0039 <0.001 Jacobsen and 

Asmund 2000 

Havnen 0.171 0.0096 <0.001 

Hundeøen <0.001 <0.001 <0.001 

St. Lawrence River in the Quebec City area, surface sediments 

TBT DBT MBT DPT mg Sn/kg dw Mean Regoli et al. 2001 

Portneuf 0.097 0.286 0.989 <0.001 

Sillery 0.146 0.165 0.087 <0.001 

Quai Lévis 0.173 0.496 0.123 0.015 

Bassin Louise 0.888 0.997 0.203 <0.001 

Outside Bassin 0.807 0.634 0.185 <0.001 

Louise 

St. Charles River 0.330 0.579 0.165 <0.001 

St. Lawrence Marina 0.209 0.389 0.004 0.101 

Île d'Orléans East 0.211 0.045 0.006 <0.001 

Superficial sediments from five river estuaries (Deba, Urola, Oria, Oiatzun, and Bidasoa) of Gipuzkoa, 

North Spain, October 2000 

TBT DBT MBT mg Sn/kg dw Range Arambarri et al. 

2003 

0.05–5.48 0.15–0.71 0.86–2.87 

Huelva coast, southwest Spain 

(November 1993– TBT DBT MBT mg Sn/kg dw Average Gomez-Ariza et 

February 1994) al. 2001 

Canela 0.0067 0.017 0.0032 

Pinillos 0.0009 0.0026 0.0015 

Carreras River 0.0140 0.080 0.015 

Idla Cristana harbor 0.090 0.090 0.035 

Cantil marina 0.100 0.270 0.080 

Punta Caiman 0.0028 0.0037 0.0012 

Isla Cristina <0.0006 <0.0007 0.0034 

breakwater (inner 

part) 

Terron harbor 28.0 46.0 45.0 

Palo 2.0 3.6 8.0 

Rompido marina 130.0 40.0 24.0 

Pino 0.8 0.7 0.9 

Punta Umbria harbor 16.0 69.0 13.0 
TIN AND TIN COMPOUNDS 268 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-2. Organotin Levels in Sediment 

Nature/location of Concentration of organotin Reported 

sediment compound Units as Reference 

Six sites from the lowermost Tennessee River and Kentucky Lake, United States, 

surface sediments (0–5 cm) 

MBT DBT TBT mg/kg dwa Range Loganathan et al. 

1999 

<0.003– <0.001– 0.0053– 

0.320 0.014 0.356 

Thirteen sites in the Sound (Øresund) between Denmark and Sweden, surface sediments, 1997 

NR NR 0.0015– mg/kg dwa Range Strand et al. 

0.0188 2003 

Twenty-four sites from Coddington Cove, Newport, Rhode Island, United States, 

surface sediments (0–2 cm), 1993 and 1994 

NR NR 0.032–0.372 mg Sn/kg dw Range Wade et al. 2004 

Eighteen sites from 11 rivers in southwest France, surface sediments, July 2001 

0.016– 0.001– 0.0013– mg Sn/kg dw Range Bancon-Montigny 

0.125 0.087 0.089 et al. 2004 

Eighteen sites from 11 rivers in southwest France, surface sediments, September 2001 

0.001– ND– ND–0.020 mg Sn/kg dw Range Bancon-Montigny 

0.048 0.037 et al. 2004 

a

Concentration reported as mg butyltin ion/kg sediment. 

DBT = dibutyltin; DPT = diphenyltin; dw = dry weight; MBT = monobutyltin; ND = not detected; NR = no data 

reported; SD = standard deviation; TBT = tributyltin; TPT = triphenyltin 
 

TIN AND TIN COMPOUNDS 269 

6. POTENTIAL FOR HUMAN EXPOSURE 

agricultural activities. Mono-, di-, and tributyltin were present in nearly all surface sediment samples 

with concentrations ranging from 0.001 to 0.125, not detected to 0.087, and not detected to 

0.089 mg Sn/kg dry weight, respectively. Mono-, di-, and triphenyltin and mono-, di-, and trioctyltin 

were also detected in some sediment samples, but with less frequency and generally at lower 

concentrations than the butyltin compounds (Bancon-Montigny et al. 2004). 

Tri-, di-, and monobutyltin were detected in all sediment samples collected in the Quebec City harbor area 

of the St. Lawrence River with concentrations of 0.097–0.888, 0.045–0.997, and 0.004–0.989 mg Sn/kg 

dry weight, respectively. Diphenyltin was detected in two sites at concentrations of 0.015 and 0.101 mg 

Sn/kg dry weight. The organotin contamination found in this study was more comparable to levels 

reported for Canadian marine harbor sites than to freshwater harbor sites (Regoli et al. 2001). Tributyltin 

and dibutyltin concentrations in surface sediments (0–2 cm) collected in 1990 and 1992 from intertidal 

sites in Portland and Boothbay Harbor, Maine ranged from 0.024 to 12.4 mg TBT/kg and from 0.015 to 

2.23 mg DBT/kg dry weight (Page et al. 1996). Tributyltin was detected in all 24 surface sediment (0– 

20 cm) samples collected from Coddington Cove, Newport, Rhode Island on November 3, 1993 and June 

13, 1994; concentrations ranged from 0.032 to 0.372 mg Sn/kg dry weight with a mean concentration of 

0.146 mg Sn/kg dry weight. Sediment cores of varying depth (up to 18 cm) were obtained from seven 

stations. Tributyltin was detected in all of these samples and ranged from 0.0073 to 0.225 mg Sn/kg dry 

weight. No consistent trends were observed in the tributyltin concentrations with depth, suggesting that 

mixing is an important process in the sediment column (Wade et al. 2004). Kentucky Lake constitutes the 

northernmost end of a shipping route for large barges and small ships between the Gulf of Mexico and the 

Ohio River. The lowermost Tennessee River receives industrial waste water from several industries in 

the Calvert City Industrial Complex. Total butyltin (BT) concentrations in the sediments of the 

lowermost Tennessee River and Kentucky Lake ranged from 0.0068 to 0.356 mg BT/kg dry weight 

(Loganathan et al. 1999). 

6.4.4 Other Environmental Media 

Tin and tributyltin concentrations found in foods are summarized in Tables 6-3 and 6-4, respectively. Tin 

concentrations of vegetables, fruits and fruit juices, nuts, dairy products, meat, fish, poultry, eggs, 

beverages, and other foods not packaged in metal cans are generally <2 mg/kg. Tin concentrations in 

pastas and breads have been reported to range from <0.003 to 0.03 mg/kg. Mean tin concentrations 

ranging from <1 to 1,000 mg/kg have been found in foods packaged in unlacquered or partially lacquered 

cans, while the average tin concentration in foods in lacquered cans has been reported to be 0–6.9 mg/kg 
TIN AND TIN COMPOUNDS 270 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-3. Tin Levels in Fooda 

Food item Concentration (mg/kg) Reported as 

Dietary intake in a French adult 

Preserved foods in unlacquered cans 

Tomatoes (n=3) 84 (46–156) Mean, range
 

Artichoke (n=1) 106
 

Mushrooms (n=3) 34 (24–45) 

Pineapples (n=5) 82 (44–136) 

Fruit cocktail (n=2) 97 (88–107) 

Peaches (n=3) 44 (27–71) 

Pears (n=2) 47 (35–60) 

Apricot (n=1) 114
 

Stewed fruit (n=1) 30
 

Grapefruit (n=1) 128
 

Preserved foods in lacquered cans 

Bean (n=1) 2.4 Mean, range 

Tomatoes (n=2) 6.0 (3.2–8.8) 

Asparagus (n=2) 3.9 (1.4–6.5) 

Garden peas (n=1) 1.0 

Mushrooms (n=2) 6.9 (0.4–13.4) 

Apricot (n=1) 5.8 

Cherry (n=1) 0.5 

Strawberry (n=1) 0.6 

Papaya (n=1) 2.9 

Meats (n=4) 4.5 (1.1–9.4) 

Fishes (n=4) 0.7 (0.3–0.9) 

Fresh foods 

Carrots (n=4) 0.08 (0.07–0.09) Mean, range
 

Cabbage (n=1) 0.06
 

Endive (n=1) 0.1
 

Spinach (n=4) <0.003 

Bean (n=1) 0.05
 

Leek (n=1) 0.03
 

Potatoes (n=5) 0.1 (0.1–0.2) 

Salad (n=4) 0.02 (0.01–0.03) 

Tomatoes (n=4) 0.05 (0.04–0.06) 

Lentils (n=2) 0.13 (0.09–0.17) 

Bananas (n=3) <0.003 

Oranges (n=3) 0.07 (0.06–0.08) 

Pears (n=3) 0.07 (0.06–0.08) 

Apples (n=4) 0.04 (0.02–0.07) 

Apricots (n=2) 0.07 (0.06–0.08) 

Alcoholic beverages (n=10) <0.003 
TIN AND TIN COMPOUNDS 271 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-3. Tin Levels in Fooda 

Food item Concentration (mg/kg) Reported as 

Mineral waters (n=5) <0.003 

Nonalcoholic beverages (n=10) 0.04 (<0.003–0.13) 

Fishes and crustaceans (n=10) <0.003 

Breads (n=6) <0.003 

Pasta (n=12) <0.003 

Meats (n=15) <0.003 

Cooked pork meats (n=10) <0.003 

Milk (n=10) <0.003 

Dairy products (n=10) <0.003 

Sugar (n=5) <0.003 

Chocolate (n=1) <0.003 

Oil (n=4) <0.003 

a

Source: Biego et al. 1999 
TIN AND TIN COMPOUNDS 272 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-4. Tributyltin (TBT) Levels in Food 

Food item Concentration (ng TBT/g) wet weight 

Seafood from eight markets worldwidea Reported as mean 

Ulsan, Korea 

Mussel, soft tissue 115
 

Shrimp, whole body 33
 

Squid, muscle 23
 

Shrimp, tail only 19
 

Chub mackerel, muscle 12
 

Flounder, muscle 9.4
 

Marseille, France 

European squid, muscle 655
 

European squid, common cuttlefish, elegant 376
 

cuttlefish, muscle 

Mediterranean mussel, soft tissue 87 

Red tuna, muscle 56 

Common cuttlefish, muscle 14 

Elegant cuttlefish, muscle 13 

Green crab, muscle 3.6 

Lemon sole, Senegalse sole, muscle Not detected 

Galveston, Texas, United States 

Pacific oyster, American oyster, soft tissue 72
 

Squid, muscle 16
 

Shrimp, whole body 12
 

Shrimp, tail only 11
 

Southern flounder, tropical flounder, muscle 6
 

Oyster, soft tissue 4.6
 

Blue runners, Atlantic bonito, muscle 4.5
 

Singapore 

Mackerel, muscle 23
 

Bigeye tuna, muscle 20
 

Mitre squid, muscle 12
 

Short-necked clam, soft tissue 5.6
 

Indian halibut, muscle 3.9
 

Crab, muscle 3.1
 

Silver pomfret, muscle 2.8
 

Stockholm, Sweden 

Atlantic herring, muscle 36
 

Common mussel, blue mussel, soft tissue 22
 

European eel, muscle 2.8
 

Plaice, muscle 2.5
 

Atlantic salmon, muscle Not detected 
TIN AND TIN COMPOUNDS 273 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-4. Tributyltin (TBT) Levels in Food 

Food item Concentration (ng TBT/g) wet weight 

Sydney, Australia 

Slimy mackerel, muscle 13
 

Sydney rock oyster, soft tissue 9.2
 

Butterfly fan lobster, muscle (tail) 7.2
 

Arrow squid, cuttlefish, muscle 7
 

Tiger flathead, muscle 6
 

Yellowtail kingfish, muscle 5.3 

Largetooth flounder, muscle 4.2
 

Halifax, Canada 

Longfin inshore squid, muscle 8.9
 

Cock shrimp, whole body 7.7
 

Common mussel, soft tissue 5.6
 

Witch flounder, muscle 2.7
 

Atlantic salmon, muscle Not detected 

Cock shrimp, tail only Not detected 

London, England 

Oyster, soft tissue 43
 

Shrimp, muscle 13.9
 

Atlantic herring, muscle 11
 

Squid, muscle 7.9
 

Mackerel, muscle 7.3
 

Mussel, soft tissue 5.9
 

Seafood from six markets in the United Statesb Reported as mean summer, winter 

San Pedro, California 

Bottom fish 7.1, 1.7 

Crustaceans 1.2, 1.1 

Mollusks 13, 1.5 

Pensacola, Florida 

Bottom fish 2.1, 1.4 

Crustaceans 1.0, 1.4 

Mollusks 2.0, no data 

Chicago, Illinois 

Freshwater fish 5.9, 3.2 

Boston, Massachusetts 

Bottom fish 1.3, 1.2 

Mollusks 3.1, 0.70 

Baltimore, Maryland 

Bottom fish 1.3, 23 

Crustaceans 1.2, 1.0 

Mollusks 3.3, 0.54 
TIN AND TIN COMPOUNDS 274 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-4. Tributyltin (TBT) Levels in Food 

Food item 

Seattle, Washington 

Bottom fish 

Crustaceans 

Pen-reared fish 

Concentration (ng TBT/g) wet weight 

0.98, 1.0 

2.4, 1.2 

5.2, 14 

a

Keithly et al. 1999 

b

Cardwell et al. 1999b 
TIN AND TIN COMPOUNDS 275 

6. POTENTIAL FOR HUMAN EXPOSURE 

(WHO 2003). Data from the Can Manufacturers Institute (CMI 1988) indicate that >90% of tin-lined 

cans used for food today are lacquered. Only light colored fruit and fruit juices are packed in unlacquered 

cans, since tin helps maintain the color of the fruit. Tin content in foods stored in opened metal cans 

increases over time, since tin can rapidly dissolve in the presence of oxygen. Acidic foods are more 

aggressive to the tin coating in metal cans, and canned acidic foods have higher tin contents. Tin 

concentrations of canned foods increase with storage time and temperature (WHO 2003). 

Tin concentrations in various foods were determined in a dietary tin intake study for adults in France. 

Foods in lacquered cans generally were found to contain tin concentrations below 10 mg/kg, and tin 

concentrations ranged from 24 to 156 mg/kg in food from unlacquered cans. The average tin 

concentration in fresh foods was 0.03 mg/kg (Biégo et al. 1999). Canned vegetables and fruit products 

were found to have mean tin concentrations of 44 and 17 mg/kg fresh weight, respectively, in a 1994 total 

diet study in the United Kingdom (Ysart et al. 1999). A study of metal concentration in canned milk 

products in Lithuania showed that the content of tin in canned milk exceeded the concentration in raw 

milk, which, in 1990–1992, was on average 0.22 mg/kg. Mean tin concentrations in evaporated sterilized 

milk, concentrated sterilized milk, and sweetened condensed milk were 85, 89, and 40 mg/kg, 

respectively. Tin concentrations in canned milk were shown to increase during storage (Ramonaiytơ

2001). Local and imported edible seaweeds obtained in British Columbia were found to contain tin in 

concentrations ranging from 0.01 to 0.46 mg/kg dry weight (van Netten et al. 2000). 

Samples of fish, crustaceans, cephalopods (i.e., squid), and bivalve mollusks were purchased from 

markets in Stockholm, Sweden; London, England; Marseille, France; Singapore; Ulsan, Korea; Sydney, 

Australia; Galveston, United States; and Halifax, Canada during August and September 1997 and 

analyzed for tributyltin content. Average tributyltin concentrations for bivalves, pelagic fish, pelagic 

invertebrates, and flatfish were 40, 16, 7.4, and 4.6 μg TBT/kg, respectively. It was noted that the high 

concentrations in bivalves were expected. The lower concentrations of tributyltin found in flatfish were 

unexpected, since flatfish live on sediment and consume mostly benthic prey. Sediment is considered a 

sink for tributyltin in aquatic environments (Keithly et al. 1999). In a similar study, seafood was 

purchased in August 1989 and January 1990, representing a summer and winter sample, from Boston, 

Massachusetts; Baltimore, Maryland; Seattle, Washington; Pensacola, Florida; San Pedro, California; and 

Chicago, Illinois. These locations represented major fishing and aquaculture areas on the coasts of the 

United States and the Great Lakes. Categories of seafood sampled were bottom fish, crustacea, 

freshwater fish, mollusks, and maricultured fish. Tributyltin was detected in 35% of samples analyzed. 

Seafood purchased during the summer was found to have slightly higher tributyltin concentrations 
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6. POTENTIAL FOR HUMAN EXPOSURE 

compared to seafood purchased in the winter in 10 of the 15 instances where the same or similar species 

were sampled from the same location during the summer and winter surveys. Elevated tributyltin 

concentrations in seafood sampled during the summer were believed to be consistent with increased 

recreational boat activity in the summer. Mean tributyltin summer concentrations for bottom fish, 

crustaceans, and mollusks were 0.98–7.1, 1.0–2.4, and 2.0–13 μg TBT/kg, respectively. Mean tributyltin 

winter concentrations for the same seafood categories were 1.0–23, 1.0–1.4, and 0.54–6.3 μg TBT/kg, 

respectively. The respective summer and winter mean concentrations of tributyltin were 5.9 and 3.2 μg 

TBT/kg in freshwater fish from Chicago, Illinois and 5.2 and 14 μg TBT/kg for pen-reared fish from 

Seattle, Washington (Cardwell et al. 1999b). 

Tributyltin and triphenyltin concentrations were determined in foods in a market basket study. About 

100 kinds of foods were purchased every year in 1990–1993 in Shiga Prefecture, Japan. Foods were 

divided into 13 groups: I, rice; II, cereals, grains, and potatoes; III, sugar and cakes; IV, fats and oils; V, 

bean products; VI, fruits; VII, green vegetables; VIII, other vegetables and seaweeds; IX, seasonal 

beverages; X, fish, mollusks, and crustaceans; XI, meats and eggs; XII, milk and dairy products; and XIII, 

cooked meats (curry and hash). Tributyltin and triphenyltin (TPT) were only detected in group X (fish, 

mollusks, and crustaceans) and group VIII (vegetables and seaweeds), with higher levels in group X 

(5.2 μg TBT and 0.4 μg TPT), than in group VIII (0.2 μg TBT and 0 μg TPT) (Tsuda et al. 1995). 

Twenty-two samples of gin, martini, cognac, red wine, and sherry that were stored in plastic containers, 

used in Canada for storage of alcoholic beverages, were analyzed for dioctyltin compounds, dioctyltin 

bis(maleate), and dioctyltin S,S'-bis(isooctyl mercaptoacetate). Beverages tested contained <40 μg/L tin. 

While these plastic containers contained up to 1,700 μg Sn/g, and these dioctyltin compounds were 

soluble in alcohol (64.7 and 150 μg/mL, respectively), there was no evidence of leaching in any samples 

analyzed (Méranger 1975). 

Tin and organotin concentrations found in human tissues and fluids are summarized in Table 6-5. Tin 

was detected in nine human adipose tissue samples during the 1982 National Human Adipose Tissue 

Survey at concentrations ranging from 4.6 to 15 μg/g (Stanley 1986). Urine samples were selected from 

the available archived urine specimens from participants in the National Health and Nutrition 

Examination Survey (NHANES) III, conducted from 1988 to 1994. The 500 samples were chosen to 

represent a broad range of the U.S. population. Tin was detected in 89% of samples (detection limit, 

0.1 μg/L) and had a 95th upper percentile concentration of 20.1 μg/L (Paschal et al. 1998). Tissue samples 

from various organs were obtained from 20 deceased individuals (15 men and 5 women), who, at the time 

of their death, lived in Terragona, Spain and the surrounding areas for at least 10 years. No known 
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6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-5. Tin and Organotin Levels in Human Tissues and Fluids 

Human tissue or fluid Concentration Units Reported as Reference 

Tin 

Adipose tissue, (n=9) 4.6–15 μg/g Range Stanley 1986 

Urine, NHANES, (n=500) 20.1 μg/L 95th upper Paschal et al. 1998 

percentile 

Urine (n=14) occupationally 1.8 (1.0–2.7) μg/L Mean (range) Schramel et al. 1997 

non-exposed men and women, 

Germany 

Terragona, Spain (n=20) 

Brain 0.98 (0.28–4.57) μg/g ww Mean (range) Llobet et al. 1998 

Bone 6.18 (2.72–17.32) 

Kidney 1.54 (0.68–3.04) 

Liver 4.44 (1.84–10.16) 

Lung 1.74 (0.67–6.54) 

Terragona, Spain (n=78) 

Brain 0.27 (0.23–0.74) μg/g ww Mean (range) García et al. 2001 

Bone 0.47 (0.45–0.76) 

Kidney 0.25 (0.23–0.43) 

Liver 0.16 (0.09–0.27) 

Lung 0.24 (0.23–0.31) 

Organotin compounds 

Blood (n=32) 

Central Michigan 

Monobutyltin 0.00817 μg/mLa Mean Kannan et al. 1999 

Dibutyltin 0.00494 

Tributyltin 0.00818 

Liver 

Poland (n=9) 

Total butyltin 0.0024–0.0110 μg/g wwa Range Kannan and Falandysz 

(MBT+DBT+TBT) 1997 

Denmark (n=18) 

Monobutyltin 0.0003–0.0047 μg/g wwa Range Nielsen and Strand 

2002 

Dibutyltin 0.0008–0.0283 

Tributyltin <0.0003 

Triphenyltin <0.003 

Japan (n=4) 

Monobutyltin 0.018 (0.012–0.022) μg/g wwa Mean (range) Takahashi et al. 1999 

Dibutyltin 0.066 (0.045–0.078) 

Tributyltin <0.0020 

a

Concentrations of organotins are reported in μg organotin species/g or mL. 

DBT = dibutyltin; MBT = monobutyltin; TBT = tributyltin; ww = wet weight 
 

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6. POTENTIAL FOR HUMAN EXPOSURE 

occupational exposure to metals was found for these subjects based on a questionnaire sent to relatives. 

Tin concentrations were lowest in brain tissue and highest in bone at 0.98 and 6.18 μg/g wet weight, 

respectively. No significant differences in tin concentrations were noted based on gender or age (Llobet 

et al. 1998). In a similar study, samples of liver, lung, kidney, brain, and bone were collected from 

78 adult subjects (57 men and 21 women) autopsied between 1997 and 1999 who at the time of death 

lived in Tarragona County, Spain or in the surroundings for the last 10 years. Autopsy records included 

data on gender, age, occupation, residence, and smoking and drinking habits. No occupational exposure 

to heavy metals was found in this group. Ages ranged from 36 to 76 years, 55% were considered 

smokers, and 24% were considered drinkers. An individual was considered a smoker if he or she smoked 

more than one pack of cigarettes per day for at least 1 year of his or her life. Men who consumed more 

than 280 g of alcohol per week (168 g for women) were considered drinkers. Place of residence was 

divided into three areas: (a) near the petrochemical industry, (b) near the petroleum refineries and 

municipal solid waste incinerator, and (c) urban area (downtown). For tin concentrations in the tissues 

studied, no significant differences between sex, smoking and drinking habits, or places of residence were 

found. One exception was in the kidney, where tin concentrations were slightly higher in drinkers (García 

et al. 2001). 

Butyltin compounds were measured in human blood collected in July 1998 in central Michigan from 

17 male and 15 female individuals. Mono-, di-, and tributyltin were detected in 53, 81, and 70% of the 

samples. Mono-, di-, and tributyltin concentrations ranged from below the detection limit to maximum 

concentrations of 0.027, 0.016, and 0.085 μg organotin ion/mL, respectively. Total butyltin 

concentrations ranged from below the detection limit to 0.101 μg BT/mL (Kannan et al. 1999). Human 

liver samples from nine individuals, aged 45–83, obtained from the Gdansk School of Medicine, Poland 

in March 1994, were found to contain total butyltin (mono-, di-, and tributyltin) concentrations ranging 

from 0.0024 to 0.011 μg BT/g wet weight (Kannan and Falandysz 1997). Four human liver samples 

obtained by autopsy in Ehime University Hospital, Japan in 1997 and 1998 were found to contain average 

concentrations of mono-, di-, tributyltin, and total butyltin of 0.018, 0.066, <0.002, and 0.084 μg 

organotin ion/g wet weight, respectively (Takahashi et al. 1999). Liver samples from 18 deceased Danish 

men aged 21–82 were collected from December 1999 to January 2000 at the Institute for Forensic 

Medicine, SDU, Odense University. Concentrations of tributyltin and triphenyltin were all below the 

detection limit, <0.0003 μg TBT/g and <0.003 μg TPT/g. Mean concentrations (and ranges) of monoand dibutyltin were 0.0016 (0.0003–0.0047) μg MBT/g and 0.009 (0.0008–0.0283) μg DBT/g wet weight. 

A large interperson variability was noted for this sample with a more than 25-fold difference between the 

lowest and highest dibutyltin liver concentration (Nielsen and Strand 2002). 
 

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6. POTENTIAL FOR HUMAN EXPOSURE 

Ten individual indoor dust samples were collected from 10 regions from the United Kingdom in 2002. 

Samples were collected primarily from private households, but also included some businesses. Samples 

were analyzed for various chemicals including eight organotin compounds, mono-, di-, tri-, and 

tetrabutyltin, mono- and dioctyltin, tricyclohexyltin, and triphenyltin. Mono-, di- and tributyltin, and 

mono- and dioctyltin were found in all pooled regional samples, and mean concentrations were 1.375, 

0.563, 0.1445, 0.4506, and 0.1292 μg organotin ion/g, respectively. Triphenyltin was found in only one 

pooled sample, at a concentration of 0.0069 μg TPT/g. Tetrabutyltin and trihexyltin were not detected. 

Detection limits were 0.001 μg organotin ion/g dry weight. Possible sources of these organotin 

compounds in the home may be from the use of butyl- and octyltin compounds as stabilizers in PVC. In 

addition, tributyltin is used as a fungicide and as treatment against dust-mites in carpets and textiles. Dust 

samples from Denmark, Finland, France, Spain, and Sweden showed similar patterns of organotin 

contents as found in the United Kingdom samples (Santillo et al. 2003). 

Tin concentrations in the kidneys of mink collected from the Kootenay River and lower Fraser River in 

British Columbia, Canada were 6.25 and 5.5 μg/g dry weight. Tin concentrations in the livers of mink 

from the upper and lower Fraser River were 5.53 and 5.17 μg/g dry weight, respectively. Tin 

concentrations in the livers of otters were <4 μg/g dry weight collected from the Kootenay, lower and 

upper Columbia, and upper Fraser Rivers, and 2.67 μg/g from the lower Fraser River (Harding et al. 

1998). Tin concentrations in mantle muscle and liver samples of juvenile Japanese common squid, 

Todarodes pacificus, collected from three locations in and near Japanese coasts, were 0.042–0.050 and 

0.077–0.13 μg/g wet weight, respectively (Ichihashi et al. 2001). 

Concentrations of butyltin (mono-, di-, and tributyltin) compounds were determined in the kidney and 

liver of 18 species of seabirds collected between the mid-1980s and mid-1990s from Japan, Korea, the 

North Pacific Ocean, and the southern Indian Ocean. The highest mean total butyltin concentrations were 

found in the kidney and liver of inland and coastal birds. The highest mean concentrations of butyltins 

(BT) were found in common cormorants from Lake Biwa, Japan at 0.300 and 0.280 μg BT/g wet weight, 

in kidney and liver, respectively. Among the open sea birds, the Laysan albatross from the North Pacific 

Ocean had the highest total butyltin concentrations in the liver at 0.043 μg BT/g wet weight (Guruge et al. 

1997). 

Concentrations of tributyltin and triphenyltin were measured in the muscle of 11 species of fish from the 

Port of Osaka and Yodo River, Japan. Concentrations of tributyltin and triphenyltin were found ranging 
 

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6. POTENTIAL FOR HUMAN EXPOSURE 

from 0.011 to 0.182 μg TBT/g and from <0.001 to 0.130 μg TPT/g wet weight. In addition, mono- and 

dibutyltin and diphenyltin were detected in all samples. Monophenyltin was detected in all but one 

sample from the Port of Osaka and none of the samples from the Yoda River (<0.001 μg MPT/g wet 

weight). Concentrations of organotin compounds were higher in fish from sea areas than those from the 

river (Harino et al. 2000). Ueno et al. (2004) determined butyltin concentrations in the liver of skipjack 

tuna (Katsuwonus pelamis) collected from Asian offshore waters, off-Seychelles (west African coast), 

off-Brazil (west South American coast), and in open seas (North Pacific) during 1996–2001. High 

concentrations of butyltins were found in skipjack tuna from offshore waters around Japan with 

concentrations up to 0.400 μg BT/g wet weight. Tributyltin was detected a relatively higher 

concentrations in all locations, with mean concentrations ranging from 0.0049 to 0.200 μg TBT/g wet 

weight in the North Pacific and the East China Sea, respectively. Monobutyltin concentrations were 

below the detection limit (0.0018 μg MBT/g) for four samples from the South China Sea, off-Indonesia, 

off-Seychelles, and off-Brazil, and ranged up to 0.017 μg MBT/g wet weight in the East China Sea (Ueno 

et al. 2004). 

Concentrations of di- and tributyltin were studied in whole-body fish samples from six freshwater sites 

across the United States (Jones-Lepp et al. 2004). Di- and tributyltin were not detected in 8 and 9 of the 

13 fish samples, respectively, that were collected from these sites (detection limits were 0.00097 and 

0.0018 μg/g for di- and tributyltin, respectively). The highest concentrations were reported in largemouth 

bass (Micropterus salmoides) from Red Bank Creek, South Carolina at 0.221 μg DBT/g , and in 

shorthead rosehorse (Moxostoma macrolepidotum) from the Little Missouri River, North Dakota at 

0.389 μg TBT/g (Jones-Lepp et al. 2004). 

Strand and Asmund (2003) studied the concentrations of butyltins in bivalves collected between 1999 and 

2000 from six areas along the west coast of Greenland. The highest tributyltin concentration, 0.254 μg 

TBT/g wet weight, was found in mussels (Mytilus edulis) sampled inside Nuuk harbor, the largest harbor 

in West Greenland. Tributyltin could only be detected in two of the six areas outside of the harbor areas 

at concentrations of 0.001 and 0.0027 μg TBT/g wet weight, in Chlamys islandica and Nuculana pernula, 

respectively. Di- and monobutyltin concentrations ranged from <0.0005 to 0.025 and from <0.0005 to 

0.0041 μg organotin ion/g wet weight, respectively, in M. edulis in the harbor sites. Di- and monobutyltin 

were not detected in C. islandica from open water sites, and were detected in N. pernula from open water 

at 0.0016 and 0.0012 μg organotin ion/g wet weight, respectively. Triphenyltin could not be detected in 

any samples (<0.005 μg TPhT/g wet weight) (Strand and Asmund 2003). M. edulis, clams (Mercenaria 

mercenaria), and fish (Tautogolabrus adspersus) collected in 1995 from Coddington Cove, Newport, 
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6. POTENTIAL FOR HUMAN EXPOSURE 

Rhode Island were found to contain tributyltin concentrations ranging from 0.0092 to 0.977 μg Sn/g wet 

weight. Tributyltin concentrations in lobsters from the same area were all below the detection limit 

(<0.006 μg Sn/g) (Wade et al. 2004). Tributyltin concentrations were measured in benthic mollusks 

(N. pernula, Nucula sulcata, Nucula tenuis, Artica islandica, Musculus niger, Cardium echinatum, 

Buccinum undatum, and Neptunea antiqua) collected in 1997 and 1999 from transects along and 

perpendicular to the shipping lanes in the Sound (Øresund) and the Kattegat/Skagerrak region, an 

important shipping strait between Denmark and Sweden. Di- and tributyltin were detected in all mollusk 

samples, and ranged from 0.011 to 0.267 μg DBT/g and from 0.0081 to 1.316 μg TBT/g dry weight 

(Strand et al 2003). Tributyltin was found in mussels (Mytilus galloprovincialis) from Portuguese coastal 

waters at concentrations of 0.011–0.789 μg Sn/g dry weight and was detected at all 17 sites sampled 

between May and July 2000. Mono- and dibutyl tin were also found in most samples with concentrations 

ranging from not quantifiable to 0.605 and from not quantifiable to 0.345 μg Sn/g dry weight, 

respectively. Di- and triphenyltin concentrations were not quantifiable in all but one sample, with a 

triphenyltin concentration of 0.016 μg Sn/g dry weight (Barroso et al. 2004). 

Tributyltin, dibutyltin, and monobutyltin concentrations were determined in the liver, kidney, and brain 

tissues of adult southern sea otters (Enhydra lutris nereis) found dead along the coast of California during 

1992–1996. The mean and range of liver, kidney, and brain concentrations for total butyltin compounds 

were 1.320 (0.040–9.2), 0.160 (0.004–0.43), and 0.061 (0.0027–0.14) μg BT/g wet weight, respectively. 

The accumulation of butyltin compounds in sea otters was explained by their bottom-feeding habit and a 

diet that consists exclusively of invertebrates such as mollusks and gastropods (Kannan et al. 1998a). 

Butyltin concentrations in the liver, kidney, and brain tissues of southern sea otters (E. lutris nereis) found 

dead on the California coast during 1992–1996 were 0.040–5.3, 0.004–0.265, and 0.0039–0.140 μg BT/g 

wet weight, respectively (Kannan et al. 2004). 

Berge et al. (2004) studied the concentrations of organotin compounds in samples of harbor porpoise 

(Phocoena phocoena), common seal (Phoca vitulina), ringed seal (Phoca hispida), and glaucous gull 

(Larus hyperboreus) from Norwegian territories without any obvious point sources of tributyltin. Most 

samples were collected between 1998 and 2000; however, some of the porpoise samples were collected in 

1988, which is prior to the restriction on the use of tributyltin on smaller boats. The highest 

concentrations of mono-, di-, and tributyltin were found in harbor porpoise samples in Northern Norway 

in 1988, especially in liver tissue with mean concentrations of 0.0345, 0.285, and 0.098 μg Sn/g wet 

weight, respectively. In general, mono-, di-, and tributyltin concentrations were lower in harbor porpoise 

tissues sampled in 1999 than in 1988. No phenyltins were found in ringed seals from Spitsbergen or in 
 

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6. POTENTIAL FOR HUMAN EXPOSURE 

glaucous gulls from Bear Island. Concentrations of phenyltins in blubber, kidney, and brain of common 

seals were below the detection limit (generally <0.001 μg Sn/g wet weight). Mono-, di-, and triphenyltin 

were detected in the liver, muscle, and kidney of harbor porpoises samples in 1999; mono- and 

diphenyltin were dominant in liver and muscle with mean concentrations of 0.0164 and 0.0192 μg Sn/g 

wet weight, respectively (Berge et al. 2004). 

Ciesielski et al. (2004) measured the organotin concentrations in liver tissue of marine mammals found 

between 1999 and 2003 from the Polish coast of the Baltic Sea. The mammals studied included 14 harbor 

porpoises (P. phocoena), 2 striped dolphins (species not specified), 1 ringed seal (P. hispida), and 2 grey 

seals (Halichoerus grypus). Tributyltin was detected in all samples and ranged from 0.044 to 1.488 μg 

Sn/g dry weight in grey seal and striped dolphin, respectively. Dibutyltin was not detected in the two 

grey seal liver samples, but was detected in all other samples ranging from 0.071 to 3.295 μg Sn/g dry 

weight in ringed seal and striped dolphin, respectively. Monobutyltin was not detected in one of the grey 

seal samples, but was detected in all other samples ranging from 0.021 to 2.915 μg Sn/g dry weight for 

grey seal and striped dolphin, respectively (Ciesielski et al. 2004). 

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE 

Human exposure to tin may occur by inhalation, ingestion, or dermal contact. However, exposure of the 

general population occurs primarily by ingestion of food (NAS 1977; WHO 1980). The daily intake from 

air is unlikely to exceed 0.5 μg based on concentrations of tin in air that have been estimated to be in the 

range of 0.002–0.03 μg/m3

 (Biégo et al. 1999). Tinplate, which is steel coated with a thin layer of 

metallic tin, has been used to line cans for food. Some of these cans are also coated with a lacquer. 

While new canning techniques have decreased the amount of tin contamination of foods over the years, 

metal cans still are the main source of tin in the diet (WHO 2003). Tin(II) chloride is used as a food 

additive and has U.S. FDA Generally Regarded As Safe (GRAS) approval. It is used as a preservative for 

canned soda water, a color retention agent in canned asparagus, and a component in food packaging 

materials (Kroschwitz and Howe 1997). Tin exposure may occur from dental preparations, since tin(II) 

fluoride (0.41%) is an approved fluoride source in dentifrices (Pader 1993). In a laboratory study to 

determine the amount of tin and other metals leached into water from copper piping with four types of 

lead-free solders, which contain 94–95.5% tin, no significant leaching of tin was observed (Subramanian 

et al. 1991). 
 

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6. POTENTIAL FOR HUMAN EXPOSURE 

Estimates of daily dietary tin intake ranged from 1 mg, for diets consisting mainly of fresh meats, 

vegetables, and cereals, to 38 mg for diets including a high proportion of canned foods (Schafer and 

Femfert 1984; WHO 1980). The average daily tin intake of an adult in the United States was estimated at 

4.003 mg (4 mg from food and 0.003 mg from air), and with undetectable levels contributed by drinking 

water (EPA 1987a; WHO 1980). Other estimates of human daily intake range from 0.2 to 17 mg 

(Klaassen et al. 1986; Krigman and Silverman 1984). Tin levels in drinking water have been reported at 

<0.010 mg/L. If daily intake of water is assumed to be 2 L/day, then intake of tin from water would be 

0.012–0.020 mg/day (WHO 2003). The tin contents in fresh food or food packaged in lacquered or 

unlacquered cans were determined to estimate the daily tin intake in an adult in France. From this study, 

it was found that canned foods, while representing 6–7% of the daily consumed foods, represented >95% 

of the total tin intake. The estimated tin intake by an adult in France was determined to be 0.04 mg/kg 

body weight (Biégo et al. 1999). In a 1994 total diet study in the United Kingdom, the canned vegetables 

group and fruit product group contributed 66 and 31%, respectively, to the total average exposure of tin, 

which was estimated as 2.4 mg/day. From this study, an upper range exposure to tin of 7.9 mg/day was 

estimated. Population dietary exposure to tin from total diet studies in the United Kingdom from 1976 to 

1994 ranged from 1.7 mg/day in 1985 to 5.4 mg/day in 1991 (Ysart et al. 1999). 

Little is known about the extent of exposure of humans to butyltin compounds (Kannan et al. 1999). 

Occupational exposure represents the greatest exposure to tributyltin; nonoccupational exposure to 

tributyltin is usually slight, with diet as the most important means of exposure (Demora and Pelletier 

1997). Dermal absorption is a significant route of occupational exposure for certain organotin 

compounds (Stewart and Lassiter 2001). Household commodities made of polyurethane, plastic 

polymers, and silicons contain butyltin concentrations in the ppm range. Butyltin compounds are also 

found in seafood (Cardwell et al. 1999b; Kannan et al. 1999; Keithly et al. 1999). The daily intakes of 

tributyltin and triphenyltin in Japan were estimated to be 4.7 and 0.7 μg in 1991 and 2.2 and 0.7 μg in 

1992, respectively, based on a duplicate portion study. In this study, cooked meals were collected for 

3 days from women in Shiga Prefecture, Japan in 1991 and 1992, and were homogenized and frozen. In a 

separate market basket study in Shiga Prefecture, Japan, daily intakes of tributyltin and triphenyltin in 

Japan were estimated to be 6.9 and 5.4 μg in 1991 and 6.7 and 1.3 μg in 1992, respectively. Of the food 

groups analyzed in the market basket study, 95% of the daily intakes of tributyltin and triphenyltin came 

from the fish, mollusks, and crustaceans food group (Tsuda et al. 1995). Human dietary exposure to 

butyltins by food in order of importance may be regarded as: marine food > animal-origin foods (dairy 

and meat) > farm products (rice, and sunflower and peanut oil) (Kannan et al. 1995). Other routes of 

exposure to organotin compounds may include leaching of organotin compounds from PVC and related 
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6. POTENTIAL FOR HUMAN EXPOSURE 

materials, which have led to contamination of food, drinking water, and municipal sewage sludges, as 

suggested in some studies. Dibutyltin and octyltin compounds have been found in some textiles products. 

It has been demonstrated that butyltin compounds in siliconized baking parchment can be transferred to 

food baked on this type of baking parchment (Takahashi et al. 1999). Organotin compounds were found 

in household dust in a U.K. study (Santillo et al. 2003). 

Occupational exposures to tin may be substantial. Inhalation or dermal exposure to triphenyltin leachate, 

used in fungicides and insecticides, may occur during both manufacturing and application (NAS 1977; 

WHO 1980). Workers in the numerous industries producing or using inorganic tin or organotin 

compounds (Section 5.3) may also be exposed. NIOSH estimated that 730,000 workers in the United 

States were potentially exposed to tin in the workplace in 1980 (NOES 1989). The National Occupational 

Exposure Survey (NOES) database does not contain information on the frequency, concentration, or 

duration of exposure to workers to tin or any of its compounds. These surveys provide only estimates of 

number of workers potentially exposed to chemicals in the workplace. 

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 Section 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). 

Exposure to tin and tin compounds for children will be similar to adults and will occur primarily through 

the diet. In a 7-day duplicate diet study of 97 pre-school aged (1.75–2.2 years) children from the 

Birmingham area in the United Kingdom, the average daily intake of tin was 1.78 mg/kg. In this study, 

mothers were asked to collect and weigh duplicate samples of all food and drink (including water) 

consumed by their children in and outside of the home. There was a significant correlation between the 
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6. POTENTIAL FOR HUMAN EXPOSURE 

amount of canned food consumed and the concentration of tin in the diet (Smart et al. 1987). Children 

living in institutional settings may be served more canned foods due to their ease of storage and 

economical price, and may be exposed to higher levels of tin than the general population (WHO 2003). 

In a joint World Health Organization (WHO) and International Atomic Energy Agency (IAEA) 

collaborative study published in 1989 on minor and trace elements in breast milk, median tin 

concentrations were 2.81 and 0.24 μg/L in breast milk from women in Guatemala and Zaire, respectively, 

3 months after giving birth (WHO/IAEA 1989). No data were located regarding current concentrations of 

tin or tin compounds in human breast milk in the United States. Other possible exposures to tin by 

children may occur from the clothing of other household members with occupational exposure (Rinehart 

and Yanagisawa 1993). 

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES 

People eating a high percentage of their diet from canned foods will be exposed to higher amounts of tin 

than the general population. For example, people living in intuitional settings, such as nursing homes, 

boarding schools, or prisons, or people with lower incomes may be served or choose canned foods due to 

their ease of storage and economical price (WHO 2003). 

Potentially high inhalation exposures to tin and its compounds may occur in the workplace or from 

agricultural uses of tin compounds. A study of the tin and lead concentrations in house dust from the 

homes of nine electrical-cable splicers employed by a large power company found higher tin 

concentrations in house dust from the splicers' homes compared to house dust from control homes. Tin 

concentrations in house dust from the homes of splicers and the controls were 117 and 14 ppm in laundry 

areas, and in other areas concentrations were 66 ppm and not detected (<10 ppm), respectively. In one of 

the control homes occupied by a person who soldered copper water pipes in his home using lead-tin 

solder, tin concentrations in dust were 5 times higher than levels found in dust from homes of either the 

control or splicer groups (Rinehart and Yanagisawa 1993). In a 1994 study of heavy metal exposure in a 

Bolivian smelter, personal breathing zone air samples were collected by 15 workers, representing 12 job 

categories during one shift according to NIOSH Method 7300. Tin exposure was below the occupational 

exposure criterion and was considered not hazardous (Sussell et al. 1996). 
 

TIN AND TIN COMPOUNDS 286 

6. POTENTIAL FOR HUMAN EXPOSURE 

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 tin and tin compounds is available. Where adequate 

information is not available, ATSDR, in conjunction with 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 tin and tin compounds. 

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. 

6.8.1 Identification of Data Needs 

Physical and Chemical Properties. Table 4-2 and Section 4.2 summarize many of the relevant 

physical and chemical properties of tin and many of its compounds. There are adequate data for the 

physical and chemical properties of tin and inorganic tin compounds. The chemical behavior of most of 

the common organotin compounds in environmentally-relevant media is not well known. There is a need 

to measure the solubility and vapor pressure of the more important organotin compounds in order to 

provide a more reliable basis for predicting their fate in the environment. 

Production, Import/Export, Use, Release, and Disposal. 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 the EPA. The TRI, which contains this 

information for 2001, became available in May of 2004. This database is updated yearly and should 

provide a list of industrial production facilities and emissions. 

Production volumes and uses of tin are well-documented (Carlin 2003b, 2004). While data were 

available on the uses of many organotin compounds, current production volumes could not be located. 

Data on releases, disposal practices, and possible environmental contamination from uses of tin and its 

compounds are limited. Since tin is not on the TRI and is not listed as an EPA hazardous waste 
TIN AND TIN COMPOUNDS 287 

6. POTENTIAL FOR HUMAN EXPOSURE 

constituent, current data are not available on industrial releases or disposal practices. Information on 

releases or disposal practices, and current quantitative data on leaching of inorganic and organic forms of 

tin into foods from tin-lined cans and PVC packaging materials would be useful in assessing potential 

human exposure to tin compounds. 

Environmental Fate. From the information available, it appears likely that both inorganic and 

organotin will partition to soils and sediments, and will not volatilize from water (Blunden et al. 1984; 

Cooney 1988; Fent 1996; Maguire et al. 1983, 1985; WHO 1980). Research on physical and biological 

processes in water and at sediment-water interfaces would be particularly helpful to more accurately 

predict the fate of tin compounds released to the environment. Methyltin compounds can be produced in 

the environment by biomethylation of inorganic tin (Fent 1996). It has been suggested that methylation 

of butyltin compounds in sediment may lead to mobilization of tin species into the water column and 

possibly to the atmosphere. However, there is currently no significant evidence of losses of organotin 

compounds to the atmosphere (Amouroux et al. 2000). 

Bioavailability from Environmental Media. Inorganic tin is not well absorbed after inhalation, 

oral, and dermal exposure. Organotin compounds are somewhat better absorbed by both the inhalation 

and oral routes (Hiles 1974; Mori et al. 1984). Dermal absorption is a significant route of occupational 

exposure for certain organotin compounds (Stewart and Lassiter 2001). The daily intakes of tin from air, 

food, and water are small (WHO 1980). Further study of human intake of organotin compounds from 

food and water would also be useful. The pH may be an important consideration for the bioavailability of 

organotin compounds. Bioconcentration studies by Looser et al. (1998) indicated that as pH increases, 

uptake of organotin compounds increases. 

Food Chain Bioaccumulation. It has been established that organotins can be bioconcentrated by 

aquatic organisms in marine environments (Gomez-Ariza et al. 2001; Harino et al. 2000; Hongxia et al. 

1998; Laughlin and Linden 1985; Looser et al. 1998; Maguire et al. 1984; Meador 2000; Suzuki et al. 

1998; Tsuda et al. 1986; Waldock and Thain 1983; Yamada and Takayanagi 1992). Similar information 

for terrestrial ecosystems would be useful. Inorganic tin compounds may also be bioconcentrated, but 

data are limited (Seidel et al. 1980; Thompson et al. 1972). There is no information available on the 

potential transfer of inorganic tin or organotin compounds from lower trophic levels to higher levels. 

This information would be useful because studies have shown that organotin can be bioconcentrated 

significantly. 
TIN AND TIN COMPOUNDS 288 

6. POTENTIAL FOR HUMAN EXPOSURE 

Exposure Levels in Environmental Media. Reliable monitoring data for the levels of tin and tin 

compounds in contaminated media at hazardous waste sites are needed so that the information obtained 

on levels of tin and tin compounds in the environment can be used in combination with the known body 

burden of tin and tin compounds to assess the potential risk of adverse health effects in populations living 

in the vicinity of hazardous waste sites. 

Data were obtained regarding tin levels in air (Dannecker et al. 1990; EPA 1982a, 1988c; NAS 1977; 

Sweet and Vermette 1993; WHO 1980). No monitoring data for concentrations of organotin compounds 

in air were found. Inorganic tin levels in water are limited to data obtained in the early 1980s (NAS 1977; 

WHO 1980) and more recent data were not found. Due to its use in marine paints, tributyltin levels, as 

well as di- and monobutyltin, levels are monitored in water (Gomez-Ariza et al. 2001; Grovhoug et al. 

1996; Hall 1988; Harino et al. 1998; Sadiki and Williams 1996, 1999; Sadiki et al. 1996; Yang and 

Maguire 2000). There have only a few surveys reported that monitor the occurrence of organotin 

compounds in U.S. freshwaters (Bancon-Montigny et al. 2004; Jones-Lepp et al. 2004). Additional 

information on inorganic and organotin concentrations in all media, especially air, water, and soil at 

hazardous waste sites, determined by the most sensitive analytical methods, would be useful in evaluating 

human exposure to tin. 

Several estimates concerning the human daily intake of tin have been reported (Biégo et al. 1999; EPA 

1987c; Klaassen et al. 1986; Krigman and Silverman 1984; WHO 1980; Ysart et al. 1999). Data on the 

intake of organotin compounds from food are limited (Cardwell et al. 1999b; Keithly et al. 1999; 

Méranger 1975; Tsuda et al. 1995). 

Exposure Levels in Humans. Tin has been detected in human adipose tissue (Stanley 1986), urine 

(Paschal et al. 1998; Schramel et al. 1997), and brain, bone, kidney, liver, and lung (García et al. 2001; 

Llobet et al. 1998). Butyltin compounds have been detected in blood (Kannan et al. 1999) and liver 

(Kannan and Falandysz 1997; Nielsen and Strand 2002; Takahashi et al. 1999). These reports are for 

populations without documented high exposures to tin and tin compounds and should represent 

background levels in human tissues. Biological monitoring data, especially for populations near 

hazardous waste sites, would help to assess human exposure to tin and tin compounds. 

This information is necessary for assessing the need to conduct health studies on these populations. 
TIN AND TIN COMPOUNDS 289 

6. POTENTIAL FOR HUMAN EXPOSURE 

Exposures of Children. Very little data were found regarding the exposure of children to tin and tin 

compounds (Smart et al. 1987; WHO 2003; WHO/IAEA 1989). Like adults, the major route of exposure 

to tin will be through the diet, particularly a diet high in canned foods. Levels of tin and organotin 

compounds in the tissue and body fluids of children have not been found. Levels of tin in human breast 

milk have been reported (WHO/IAEA 1998); however, more recent tin concentrations in human breast 

milk have not been found. 

Child health data needs relating to susceptibility are discussed in Section 3.12.2, Identification of Data 

Needs: Children’s Susceptibility. 

Exposure Registries. No exposure registries for tin and tin compounds were located. Tin and tin 

compounds are not currently substances for which a sub-registry has been established in the National 

Exposure Registry. Tin and tin compounds will be considered in the future when chemical selection is 

made for sub-registries 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 these substances. 

6.8.2 Ongoing Studies 

The Federal Research in Progress (FEDRIP 2004) database provides additional information obtainable 

from a few ongoing studies that may fill in some of the data needs identified in Section 6.8.1. These 

studies are summarized in Table 6-6. 

The Organotin Environmental Programme (ORTEP) Association is an international non-profit 

organization of producers of organotin compounds established in 1978 by companies from the United 

States, Europe, and Japan. The goals of the ORTEP Association include the promotion and 

encouragement of the dissemination of scientific and technical information on the environmental effects 

of organotin compounds (ORTEP 2004). The International Tin Research Institute (ITRI) tin producers 

announced, in October 20, 2004, a project that will begin in January 2005 that will generate information 

to increase the understanding of the tin industry, and the applications of tin, as well as the interactions of 

tin with humans and the environment, including increased scientific understanding of the environmental 

fate of tin during its use and recycling (Tin Technology 2004). 
TIN AND TIN COMPOUNDS 290 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-6. Ongoing Studies on Organotin Compoundsa 

Investigator Affiliation Research description Sponsor 

Eng G University of the 

District of 

Columbia 

Investigation of the environmental fate of triorganotins 

that leach in the aerobic and anaerobic sediments of 

D.C. waterways and determination of the toxicity of 

these compounds on the aquatic biota. 

Department of 

Agriculture 

Pannell KH University of 

Texas at El Paso 

The investigators propose to continue their initially 

successful study concerning the synthesis and 

biocidal evaluation of new organotin materials and 

compounds. 

National 

Institutes of 

Health 

a

FEDRIP 2004 
 

TIN AND TIN COMPOUNDS 291 

7. ANALYTICAL METHODS 

The purpose of this chapter is to describe the analytical methods that are available for detecting, 

measuring, and/or monitoring tin and tin compounds, their metabolites, and other biomarkers of exposure 

and effect to tin and tin compounds. 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. 

Tin is usually determined as the total metal, but it may also be measured as specific organotin 

compounds. Flame atomic absorption analysis is the most widely used and straightforward method for 

determining tin; furnace atomic absorption analysis is used for very low analyte levels and inductively 

coupled plasma atomic emission analysis is used for multianalyte analyses that include tin. 

The preferred separation technique for organotin compounds is gas chromatography (GC) due to its high 

resolution and detector versatility. Analysis of organotin compounds usually consists of four steps: 

(1) extraction; (2) formation of volatile derivative; (3) separation; and (4) detection and quantification. 

First, the organotin compounds must be extracted from the sample using organic solvents, ion exchange 

resins, or adsorption onto a solid support. For biological materials, a general clean-up step is needed, 

such as purification using Florisil, silica gel, alumina, or ion exchange resin. The extracted organotin 

compounds must then undergo derivatization to a volatile form to be able to separate them by GC. 

Derivatization methods include the formation of alkyl (methyl or pentyl) derivatives using a Grinard 

reagent, formation of ethyl derivatives using sodium tetraethylborate, or by formation of hydrides 

(RnSnH4-n) using sodium borohydride. Separation of these derivatives may be done using differences in 

their boiling points or by GC. Finally, detection and quantification can be performed using a flame 

photometric detector, atomic absorption spectroscopy (AAS), or mass spectrometry (MS) (Takeuchi et al. 

2000; WHO 1990). 

High performance liquid chromatography (HPLC) has also been used in the analysis of organotin 

compounds. The advantage of HPLC over GC is that no derivatization step is needed after extraction. 
 

TIN AND TIN COMPOUNDS 292 

7. ANALYTICAL METHODS 

Most separations are based on ion exchange or reversed phase separations using gradient elution. AAS, 

inductively coupled plasma mass spectrometry (ICP-MS), and fluorometric detection can be used. HPLC 

coupled with AAS is commonly used for speciation of organotin compounds (Takeuchi et al. 2000). 

7.1 BIOLOGICAL MATERIALS 

Tin and its compounds can enter the human body through inhalation, ingestion, or penetration through the 

skin. Levels of tin and tin compounds in the body can be estimated by analysis of body fluids, excreta, or 

tissues. Methods for the determination of tin in biological materials are summarized in Table 7-1. 

Normally, for determination in biological samples, the sample is digested in an oxidizing acid mixture 

followed by atomic spectrometric determination. Determination of organotin compounds in biological 

materials will require extraction, derivatization, separation, and detection, as described above. Human 

exposure to elemental tin and organotin compounds may be determined by analysis of blood or urine. 

Whole blood samples are typically analyzed by spectrophotometry and photometry. Urine samples may 

be acid digested to destroy organic matter and to oxidize tin to the tin(IV) state (Stewart and Lassiter 

2001). 

7.2 ENVIRONMENTAL SAMPLES 

Methods for determination of tin in environmental samples are summarized in Table 7-2. 

Tin is readily measured in multielement analyses of air, water, and solid waste samples by inductively 

coupled plasma-atomic emission spectroscopy (ICP-AES). For samples that are free of particulate matter, 

such as drinking water, direct aspiration atomic absorption spectroscopy, such as EPA Method 7870, may 

be used. Other samples, such as groundwater, industrial wastes, soils, sediments, sludges, and other solid 

wastes, require digestion prior to analysis to determine total and acid leachable metal (EPA 1992). EPA 

Method 3050B, which describes acid digestion of sediments, sludges, and soils, does not list tin as an 

analyte; however, it states other elements and matrices may be analyzed by this method if performance is 

demonstrated for that analyte in that matrix at the concentrations of interest (EPA 1996b). 

The APHA methods using either a flame atomic absorption method (3111B) or electrochemical atomic 

absorption method (3113B) may be used for analysis of tin in water, depending on the sensitivity desired. 
TIN AND TIN COMPOUNDS 293 

7. ANALYTICAL METHODS 

Table 7-1. Analytical Methods for Determining Inorganic Tin and Organotin 

Compounds in Biological Materials 

Sample 

matrix Preparation method 

Analytical 

method 

Sample 

detection limit 

Percent 

recovery Reference 

Total inorganic tin 

Biological 

materiala 

Urine 

Digestion of 

biological materials 

Digest in oxidizing 

acid, extract ketone 

as the cupferon 

chelate 

Atomic 

spectrometric 

Colorimetry 

No data 

<50 μg/Lb 

No data 

98–106% 

Angerer and 

Schaller 1988 

Baselt 1988 

Urine Extraction with 

polydithiocarbamate 

resin, which is ashed 

ICP-AES 2 μg/L 100±10% 

recovery 

Kneip and Crable 

1988 

Urine Extract with resin, 

ash resin 

ICP-AES 0.1 μg 100±10% NIOSH 1984a 

Food Digest in oxidizing 

acid 

AAS No data No data AOAC 1990a 

Urine Extract with resin, 

ash resin 

ICP-AES 0.1 μg/sample 100% NIOSH 1994a 

Blood Wet ashing with nitric 

and perchloric acids 

AAS 2.5 ng/mL No data Chiba et al. 1994 

Urine Acidified with nitric 

acid 

ICP-MS 0.05 μg/L 95.5% Schramel et al. 

1997 

Organotins and metabolites 

Biological 

materials, 

tissue 

Homogenized, 

hydrochloric acid 

added, extracted with 

ethyl acetate 

HPLC/ 

fluorescencec 

0.1–1 ng 

depending on 

the dialkyltin 

species 

91–100% Yu and Arakawa 

1983 

Biological 

materials 

Elution stepwise on 

silica gel column 

AAS 1.5 ng Sn 72.7±9.3% Iwai et al. 1981 

Human liver Acidified tissue 

extracted with 0.1% 

tropolone-acetone, 

derivatization with 

GC-FPD 5 ng/g (TBT) 

1 ng/g (DBT, 

MBT) 

No data Kannan and 

Falandysz 1997 

propyl magnesium 

bromide 

Human liver Homogenized with 

0.1% tropoloneacetone/HCl, 

dervatized with 

GC-FPD 4.0 ng/g (TBT) 

3.0 ng/g (DBT) 

2.0 ng/g (MBT) 

No data Takahashi et al. 

1999 

propyl magnesium 

bromide 
TIN AND TIN COMPOUNDS 294 

7. ANALYTICAL METHODS 

Table 7-1. Analytical Methods for Determining Inorganic Tin and Organotin 

Compounds in Biological Materials 

Sample Analytical Sample Percent 

matrix Preparation method method detection limit recovery Reference 

Human liver Acid digestion, GC-PFPD 0.3 ng/g (TBT) No data Nielson and 

derivatization with 3 ng/g (DBT, Strand 2002 

sodium MBT) 

tetraethylborate 

a

A digestion procedure for metals in biological materials applicable to most metals, including tin. 

b

Estimated from sensitivity and linearity data. 

c

Fluorescence detection after derivitization with Morin reagent. 

AAS = atomic absorption spectroscopy; DBT = dibutyltin; FPD = flame photometric detector; GC = gas 

chromatography; HCl = hydrochloric acid; HPLC = high performance liquid chromatography; ICP-AES = inductively
 

coupled plasma-atomic emission spectroscopy; ICP-MS = inductively coupled plasma mass spectrometryl; 

MBT = monobutyltin; PFPD = pulsed flame photometric detector; TBT = tributyltin 
TIN AND TIN COMPOUNDS 295 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Inorganic Tin and Organotin 

Compounds in Environmental Samples 

Sample 

Analytical detection Percent 

Sample matrix Preparation method method limit recovery Reference 

Total inorganic tin 

Environmental Digested in oxidizing acid ICP-MS 0.04–50 ng/g 103±3% BrzezinskaPaudyn and 

Van Loon 1988 

Water Generate hydride with AAS 0.02 μg/L No data Rains 1982 

sodium borohydride or 

electrolytically, sweep into 

silica cell heated to 700 °C 

Water Generate hydride with AAS 0.5 μg/L No data Thompson and 

(aqueous sodium borohydride or Thomerson 

solution) electrolytically, sweep into 1974 

silica cell heated to 700 °C 

Water Acidify with nitric acid AAS (direct 0.8 mg/L No data APHA 1998a 

aspiration) 

Water Acidify with nitric acid AAS (furnace 5 μg/L No data APHA 1998b 

technique) 

Watera Acidify with nitric acid ICP-AES No data No data APHA 1998c 

Water Acidify with nitric acid AAS (direct 0.8 mg/L No data EPA 1986b, 

aspiration) 1992, 1996b 

Pesticide Form volatile organotin GC-FID No data No data Basters et al. 

formulations derivatives 1978 

Organotins 

Pesticide Derivatize butylmagnesium GC-FID No data No data AOAC 1990a 

formulations chloride, extract with 

toluene 

Air Adsorbed onto GC-FID 0.05 μg/m3 93.3±9.3% Zimmerli and 

Chromosorb 102 Zimmermann 

desorption with ethereal 1980 

hydrochloric acid, 

methylated 

Airb Adsorption on filter and HPLC-AAS 1 μg/sample No data NIOSH 1994b 

XAD-2 resin, desorption (furnace 

technique) 

Airc Adsorption on filter and GC-FPD 0.01 μg No data NIOSH 2002 

XAS-2 resin, desorption, 

derivatization with sodium 

tetraethylborate 

Water Acidified, extracted with GC-FPD 100 pg 96±4 to Maguire and 

tropolone benzene, 103±8% Huneault 1981 

derivatized 
TIN AND TIN COMPOUNDS 296 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Inorganic Tin and Organotin 

Compounds in Environmental Samples 

Sample 

Analytical detection Percent 

Sample matrix Preparation method method limit recovery Reference 

Water Generate hydrides with AAS 2 ng No data Hodge et al. 

sodium borohydride, 1979 

separate hydrides by 

boiling point 

Water Generate hydride AAS <0.1 μg/L No data Lee et al. 1989 

derivatives tributyltin 

Water Extract in n-hexane, Fluorescence 0.001– 91.3±0.6 to Arakawa et al. 

produce fluorescent morin 0.5 nmol/mL 99.7±0.5% 1983 

derivative recovery 

Sediment Organotin compounds are GC-MS 0.07 ng Sn/g 80–90% Muñoz et al. 

complexed with NaDCC (MBT); (MBT); 85– 2004 

and retained on a C60 0.09 ng Sn/g 95% (DBT 

column; complexes are (DBT); and TBT) 

eluted with EtOAc 0.10 ng Sn/g 

containing NaBPr4 (TBT) 

a

Tin not listed specifically as an analyte, but can be determined by ICP-AES. 

b

Method was validated with tetrabutyltin, tributyltin chloride, tricyclohexyltin hydroxide, and dibutyltin 

bis(isooctylmercaptoacetate).

c

This method was developed for air monitoring of methyltin chlorides. 

AAS = atomic absorption spectroscopy; DBT = dibutyltin; EtOAc = ethyl acetate; GC-FID = gas chromatographyflame ignition detector; GC-FPD = gas chromatography-flame photometric detector; GC-MS = gas chromatography
 

mass spectrometry; ICP-AES = inductively coupled plasma-atomic emission spectroscopy; ICP-MS = inductively
 

coupled plasma-mass spectrometry; MBT = monobutyltin; NaBPr4 = sodium tetra-n-propylborate; NaDCC = sodium 

diethyldithiocarbamate; TBT = tributyltin 
TIN AND TIN COMPOUNDS 297 

7. ANALYTICAL METHODS 

While tin is not specifically listed as an analyte for the ICP-MS method (3125), it may also be used in 

most cases and has lower detection limits (APHA 1998a, 1998b, 1998c). 

Organotin can be extracted from environmental samples and determined by AAS or GC methods, usually 

after derivatization and separation. NIOSH Method 5504 allows for analysis of organotin compounds (as 

tin) in air and was validated using tetrabutyltin, tributyltin chloride, tricyclohexyltin hydroxide, and 

dibutyltin bis(isooctylmercaptoacetate) (NIOSH 1994b). NIOSH Method 5526 was developed for air 

monitoring of monomethyltin trichloride, dimethyltin dichloride, and trimethyltin chloride (NIOSH 

2002). 

Muñoz et al. (2004) described a new method for the speciation of butyltin compounds where the 

compounds were complexed with sodium diethyldithiocarbamate and retained on a fullerene C60 sorbent 

column. The neutral butyltin complexes were then eluted with ethyl acetate containing sodium tetran-propylborate as a derivatizing agent, and the eluent was then analyzed using GC/MS. By 

preconcentrating the organotin compounds on the C60 sorbent, this method allows for determination of 

mono-, di-, and tributyltin in the ng/g range. Detection limits of 0.07, 0.09, and 0.10 ng Sn/g for mono-, 

di-, and tributyltin, respectively, were reported. Recoveries were reported to be 80–90% for monobutyltin 

and 85–95% for di- and tributyltin. Validation of this method was carried out by the analysis of a 

standard reference sediment (Muñoz et al. 2004). 

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 tin and tin compounds is available. Where adequate 

information is not available, ATSDR, in conjunction with 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 tin and tin compounds. 

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. 
TIN AND TIN COMPOUNDS 298 

7. ANALYTICAL METHODS 

7.3.1 Identification of Data Needs 

Methods for Determining Biomarkers of Exposure and Effect. Sensitive and selective 

methods are available for the detection and quantitative measurement of tin after the sample matrix in 

which it is contained has been properly treated. Atomic spectrometric techniques provide methods for the 

determination of tin with low detection limits that are highly specific are readily available (Angerer and 

Schaller 1988; AOAC 1984b; Kneip and Crable 1988; NIOSH 1984a). Methods for the determination of 

specific compounds that contain tin are more difficult and less well developed than are methods for the 

determination of total tin, but determination of specific tin compounds is an important concern because of 

the widespread use of organotin compounds as preservatives in industry and in other applications. 

Exposure. Methods exist to determine inorganic and organic tin levels in environmental samples and 

human tissues. However, no methods have been identified that can be used to correlate the level and 

extent of exposure to tin and specific tin compounds with levels of tin in biological materials such as 

human tissues or fluids. It would be useful to have such methods to make these correlations; however, it 

is not likely that such a method will be developed. 

Effect. No methods have been identified that can be used to directly associate levels of tin and specific 

tin compounds in biological samples with the onset of adverse health effects. If such methods were 

available, it would be possible to correlate the level or severity of effects with the level and extent of 

exposure. 

Methods for Determining Parent Compounds and Degradation Products in Environmental 

Media. Methods for determining tin in water, air, and waste samples with excellent selectivity and 

sensitivity are well developed and undergoing constant improvement. 

Sampling methodologies for very low level elemental pollutants such as tin continue to pose problems, 

including nonrepresentative samples, insufficient sample volumes, contamination, and labor-intensive, 

tedious extraction, and purification procedures (Green and LePape 1987). 
TIN AND TIN COMPOUNDS 299 

7. ANALYTICAL METHODS 

7.3.2 Ongoing Studies 

No ongoing studies involving analytical techniques of tin or tin compounds were found in a search of 

Federal Research in Progress (FEDRIP 2004). 

TIN AND TIN COMPOUNDS 301 

8. REGULATIONS AND ADVISORIES 

The international, national, and state regulations and guidelines regarding tin and tin compounds in air, 

water, and other media are summarized in Table 8-1. 

ATSDR derived an intermediate-duration oral MRL for inorganic tin of 0.3 mg Sn/kg/day (as stannous 

chloride) based on a NOAEL of 32 mg/kg/day for hematological effects in rats in a 90-day feeding study 

(De Groot et al. 1973). An uncertainty factor of 100 was applied to the NOAEL (10 for animal to human 

extrapolation and 10 for human variability). 

ATSDR derived an intermediate-duration oral MRL of 0.005 mg/kg/day for dibutyltin chloride based on a 

LOAEL of 5 mg/kg/day for immunological effects in rats in a 4–6-week feeding study (Seinen et al. 

1977b). An uncertainty factor of 1,000 was applied to the LOAEL (10 for animal to human extrapolation, 

10 for the use of a LOAEL, and 10 for human variability). 

ATSDR derived an intermediate-duration oral MRL of 0.0003 mg/kg/day for tributyltin oxide based on a 

NOAEL of 0.025 mg/kg/day for immunological effects in rats in a 4.5–6-month dietary study in rats (Vos 

et al. 1990). An uncertainty factor of 100 was applied to the NOAEL (10 for animal to human 

extrapolation and 10 for human variability). 

ATSDR derived a chronic-duration oral MRL of 0.0003 mg/kg/day for tributyltin oxide based on a 

NOAEL of 0.025 mg/kg/day for immunological effects in rats in an 18-month dietary study in rats (Vos 

et al. 1990). An uncertainty factor of 100 was applied to the NOAEL (10 for animal to human 

extrapolation and 10 for human variability). 

EPA (IRIS 2005) derived an oral reference dose (RfD) of 0.0003 mg/kg/day for tributyltin oxide using a 

benchmark dose analysis of immunological effects in rats in an 18-month dietary study (Vos et al. 1990). 

A 10% relative change was chosen as the benchmark response (BMR). 

EPA (IRIS 2005) has assigned tributyltin oxide to group D weight-of-evidence classification: not 

classifiable as to human carcinogenicity, or to a group for which there is “inadequate information to 

assess carcinogenic potential,” according to updated guidelines (EPA 2003g). 
 

 

TIN AND TIN COMPOUNDS 302 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Tin and Tin Compounds 

Agency Description	 Information Reference 

INTERNATIONAL 

Guidelines: 

IARC Carcinogenicity classification 

WHO Drinking water guideline 

Tin and inorganic tin compounds 

NATIONAL 

Regulations and Guidelines: 

a. Air: 

ACGIH TLV (8-hour TWA) 

Tin (as Sn) 

Metal 

Oxide and inorganic compounds, 

except tin hydride 

Organic compoundsa

 STEL 

NIOSH REL (10-hour TWA) 

Tin (as Sn) 

Inorganic compounds, except tin 

oxides

 IDLH 

Organic compounds, except 

cyhexatinb

 IDLH 

 Stannous oxide 

OSHA PEL (8-hour TWA) for general 

industry 

Tin (as Sn) 

Inorganic compounds, except 

oxides 

Organic compounds 

PEL (8-hour TWA) for 

construction industry 

Tin (as Sn) 

Inorganic compounds, except 

oxides 

Organic compounds 

OSHA PEL (8-hour TWA) for shipyard 

industry 

Tin (as Sn) 

Inorganic compounds, except 

oxides 

Organic compounds 

Tin oxide (as Sn) 

Total dust 

Respirable fraction 

No data 

No numerical value based 

on low toxicity 

2.0 mg/m3 

2.0 mg/m3 

0.1 mg/m3 

0.2 mg/m3 

2.0 mg/m3 

100 mg/m3 

0.1 mg/m3 

25 mg/m3 

2.0 mg/m3 

2.0 mg/m3 

0.1 mg/m3 

2.0 mg/m3 

0.1 mg/m3 

2.0 mg/m3 

0.1 mg/m3 

15 mg/m3 

5.0 mg/m3 

WHO 1993 

ACGIH 2003 

NIOSH 2003a, 2003b 

OSHA 2003a 

29 CFR 1910.1000, 

Table Z-1 

OSHA 2003c 

29 CFR 1926.55, 

Appendix A 

OSHA 2003b 

29 CFR 1915.1000 
 

 

 

 

TIN AND TIN COMPOUNDS 303 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Tin and Tin Compounds 

Agency Description Information Reference 

NATIONAL (cont.)

 USNRC Occupational values 

Oral ingestion for Class Dc 

110Tin 

111Tin 

ALI (μCi) 

4.0x103 

7.0x104 

USNRC 2003 

10 CFR 20, 

Appendix B 

113Tin (LLI wall)d 

113Tin 

2.0x103 

2.0x103 

117mTin (LLI wall)d 

117mTin 

2.0x103 

2.0x103 

119mTin (LLI wall)d 

119mTin 

3.0x103 

4.0x103 

121Tin (LLI wall)d 

121Tin 

6.0x103 

6.0x103 

121mTin (LLI wall)d 

121mTin 

3.0x103 

4.0x103 

123Tin (LLI wall)d 

123Tin 

5.0x102 

6.0x102 

123mTin 5.0x104 

125Tin (LLI wall)d 

125Tin 

4.0x102 

5.0x102 

126Tin 3.0x102 

127Tin 7.0x103 

128Tin 9.0x103 

Occupational values

 Inhalatione

 for Class Dc 

110Tin 

111Tin 

ALI (μCi) 

1.0x104 

2.0x105 

DAC (μCi/mL) 

5.0x10-6 

9.0x10-5 

USNRC 2003 

10 CFR 20, 

Appendix B 

113Tin 1.0x103 5.0x10-7 

117mTin (bone and surf)d 

117mTin 

1.0x103 

2.0x103 

No data 

5.0x10-7 

119mTin 2.0x103 1.0x10-6 

121Tin 2.0x104 6.0x10-6 

121mTin 9.0x102 4.0x10-7 

123Tin 6.0x102 3.0x10-7 

123mTin 1.0x105 5.0x10-5 

125Tin 9.0x102 4.0x10-7 

126Tin 6.0x101 2.0x10-8 

127Tin 2.0x104 8.0x10-6 

128Tin 3.0x104 1.0x10-5 
 

TIN AND TIN COMPOUNDS 304 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Tin and Tin Compounds 

Agency Description Information Reference 

NATIONAL (cont.)

 USNRC Occupational values 

Inhalatione

 for Class Wf 

110Tin 

111Tin 

113Tin 

117mTin 

119mTin 

121Tin 

121mTin 

123Tin 

123mTin 

125Tin 

126Tin 

127Tin 

128Tin 

b. Water 

EPA Drinking water standards 

c. Food 

FDA Direct food substances affirmed 

as GRAS in accordance with 

good manufacturing practices; 

stannous chloride (anhydrous 

and dehydrated) 

Food additives permitted for 

direct addition to food for human 

consumption; stannous chloride 

(food additive) may be safely 

used for color retention in 

asparagus packed in glass, with 

lids lined with an inert material 

Indirect food additives; 

adhesives; bis(tributyltin)oxide 

Indirect food additives; polymers; 

polyurethane resins 

Indirect food additives; resinous 

and polymeric coatings 

Indirect food additives; rubber 

articles intended for repeated 

use; stannous chloride 

Substances GRAS in 

accordance with good 

manufacturing or feeding 

practices; stannous chloride 

d. Other 

ACGIH Carcinogenicity classification 

EPA Carcinogenicity classification 

 Bis(tributyltin oxide) 

ALI (μCi) 

1.0x104 

DAC (μCi/mL) 

5.0x10-6 

3.0x105 1.0x10-4 

5.0x102 2.0x10-7 

1.0x103 6.0x10-7 

1.0x103 4.0x10-7 

1.0x104 5.0x10-6 

5.0x102 2.0x10-7 

2.0x102 7.0x10-8 

1.0x105 6.0x10-5 

4.0x102 1.0x10-7 

7.0x101 3.0x10-8 

2.0x104 8.0x10-6 

4.0x104 1.0x10-5 

No data 

Not to exceed 0.0015% 

calculated as tin for all food 

categories 

Not to exceed 20 pmm 

calculated as tin 

For use as a preservative 

only 

Dibutyltin chloride 

Stannous chloride 

Activators (total not to 

exceed 5% by weight of 

rubber product) 

Not to exceed 0.0015% 

calculated as tin 

A4g 

Dh 

USNRC 2003 

10 CFR 20, 

Appendix B 

FDA 2003a 

21 CFR 184.1845 

FDA 2003b 

21 CFR 172.180 

FDA 2003d 

21 CFR 175.105(c)(5) 

FDA 2003e 

21 CFR 177.1680(b) 

FDA 2003c 

21 CFR 175.300 

FDA 2003f 

21 CFR 

177.2600(c)(4) 

FDA 2003g 

21 CFR 582.3845 

ACGIH 2003

IRIS 2005 
 

 

 

 

TIN AND TIN COMPOUNDS 305 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Tin and Tin Compounds 

Agency Description Information Reference 

NATIONAL (cont.)

 EPA RfD

 Bis(tributyltin oxide) 

RfC

 Bis(tributyltin oxide) 

Community right-to-know; 

release reporting; effective date 

of reporting 

Bis(tributyltin)oxide 

 Triphenyltin chloride 

Emergency release notification 

Extremely hazardous 

 Trimethyltin chloride 

Reportable quantity 

Threshold planning quantity

 Triphenyltin chloride 

Reportable quantity 

Threshold planning quantity 

Municipal solid waste landfills; 

hazardous constituent; tin (total) 

Notification requirements of 

releases 

Standards for owners and 

operators of hazardous waste 

TSD facilities; groundwater 

monitoring; tin (total) 

USNRC Effluent concentrations for 

Class Dc 

110Tin 

111Tin 

113Tin (LLI wall)d 

113Tin 

117mTin 

119mTin (LLI wall)d

 19mTin 

121Tin (LLI wall)d 

121Tin

 121mTin (LLI wall)d

 121mTin 

123Tin (LLI wall)d 

123Tin 

123mTin 

125Tin (LLI wall)d 

125Tin 

126Tin 

127Tin 

128Tin 

IRIS 2005 

IRIS 2005 

EPA 2003f 

40 CFR 372.65 

EPA 2003c 

40 CFR 355.40 

EPA 2003d 

40 CFR 355, 

Appendix A 

EPA 2003a 

40 CFR 258, 

Appendix II 

EPA 2003b 

40 CFR 302.6 

EPA 2003e 

40 CFR 264, 

Appendix IX 

USNRC 2003 

10 CFR 20, 

Appendix B 

3x10-4 mg/kg/day 

No data 

01/01/95 

01/01/95 

Tin 

500 pounds 

500/10,000 pounds 

500 pounds 

500/10,000 pounds 

Method 

6010 

Tin 

Method 

7870 

Air (μCi/mL) 

2.0x10-8 

3.0x10-7 

2.0x10-9 

No data 

3.0x10-9 

3.0x10-9 

No data 

2.0x10-8 

No data 

1.0x10-9 

No data 

9.0x10-10 

No data 

2.0x10-7 

1.0x10-9 

No data 

8.0x10-11 

3.0x10-8 

4.0x10-8 

PQL 

40 μg/L 

PQL 

8x103 μg/L 

Water (μCi/mL) 

5.0x10-5 

1.0x10-3 

No data 

3.0x10-5 

3.0x10-5 

No data 

6.0x10-5 

No data 

8.0x10-5 

No data 

5.0x10-5 

No data 

9.0x10-6 

7.0x10-4 

No data 

6.0x10-6 

4.0x10-6 

9.0x10-5 

1.0x10-4 
TIN AND TIN COMPOUNDS 306 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Tin and Tin Compounds 

Agency Description Information Reference 

NATIONAL (cont.) 

USNRC Effluent concentrations for USNRC 2003 

Class Wf 

110Tin 

111Tin 

Air (μCi/mL) 

2.0x10-8 

4.0x10-7 

10 CFR 20, 

Appendix B 

113Tin 8.0x10-10 

117mTin 2.0x10-9 

119mTin 1.0x10-9 

121Tin 2.0x10-8 

121mTin 8.0x10-10 

123Tin 2.0x10-10 

123mTin 2.0x10-7 

125Tin 5.0x10-10 

126Tin 9.0x10-11 

127Tin 3.0x10-8 

128Tin 5.0x10-8 

Release to sewers for Class Dc; USNRC 2003 

monthly average concentration 110Tin 

111Tin 

113Tin 

117mTin 

119mTin 

121Tin

 121mTin 

123Tin 

123mTin 

125Tin 

126Tin 

127Tin 

128Tin 

5.0x10-4 μCi/mL 

1.0x10-2 μCi/mL 

3.0x10-4 μCi/mL 

3.0x10-4 μCi/mL 

6.0x10-4 μCi/mL 

8.0x10-4 μCi/mL 

5.0x10-4 μCi/mL 

9.0x10-5 μCi/mL 

7.0x10-3 μCi/mL 

6.0x10-5 μCi/mL 

4.0x10-5 μCi/mL 

9.0x10-4 μCi/mL 

1.0x10-3 μCi/mL 

10 CFR 20, 

Appendix B 

STATE 

a. Air No data 

b. Water 

Florida Drinking water guideline HSDB 2003 

Tin 4.2 mg/L 

Minnesota Drinking water guideline HSDB 2003 

Tin 4.0 mg/L 
TIN AND TIN COMPOUNDS 307 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Tin and Tin Compounds 

Agency Description Information Reference 

STATE (cont.) 

c. Food No data 

d. Other No data 

a

Skin notation: refers to the potential significant contribution to the overall exposure by the cutaneous route, including
 

mucous membranes and the eyes, either by contact with vapors or, of probable greater significance, by direct skin 

contact with the substance. 

b

Skin designation 

c

Class D: refers to the retention (clearance half-times of <10 days) for all compounds except those given for W. d

When an ALI is defined by the stochastic dose limit, this value alone, is given. When an ALI is determined by the 

non-stochastic dose limit to an organ, the organ or tissue to which the limit applies is shown, and the ALI for the 

stochastic limit is shown in parentheses. (Abbreviated organ or tissue designations are used: LLI wall = lower large 

intestine wall; St. wall = stomach wall; Blad wall = bladder wall; and Bone surf = bone surface.) e

The ALIs and DACs for inhalation are given for an aerosol with an activity median aerodynamic diameter (AMAD) of 

1 μm and for class D and W of radioactive material, which refers to their retention (clearance half-times of <10 days 

and 10–100 days, respectively) in the pulmonary region of the lung. 

f

Class W: refers to the retention (clearance half-times of 10–100 days) for sulfides, oxides, hydroxides, halides, 

nitrates, and stannic phosphate. 

g

A4: not classifiable as a human carcinogen 

h

D: not classifiable as to human carcinogenicity
 

ACGIH = American Conference of Governmental Industrial Hygienists; ALI = annual limits on intakes; CFR = Code of 

Federal Regulations; DAC = derived air concentration; EPA = Environmental Protection Agency; FDA = Food and 

Drug Administration; GRAS = generally recognized as safe; HSDB = Hazardous Substances Data Bank;
 

IARC = International Agency for Research on Cancer; IDLH = immediately dangerous to life or health; 

IRIS = Integrated Risk Information System; LLI = lower large intestine; NIOSH = National Institute for Occupational 

Safety and Health; OSHA = Occupational Safety and Health Administration; PEL = permissible exposure limit; 

PQL = practical quantitation limit; REL = recommended exposure limit; RfC = inhalation reference concentration; 

RfD = oral reference dose; STEL = short-term exposure level; TLV = threshold limit values; TSD = treatment, 

storage, and disposal; TWA = time-weighted average; USNRC = Nuclear Regulatory Commission; WHO = World 

Health Organization 

 

 

_______________________ 

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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 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 that 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. 
TIN AND TIN COMPOUNDS 372 

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 of people that 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. 

Immunologic Toxicity—The occurrence of adverse effects on the immune system that may result from 

exposure to environmental agents such as chemicals. 
TIN AND TIN COMPOUNDS 373 

10. GLOSSARY 

Immunological Effects—Functional changes in the immune response. 

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. 

Intermediate Exposure—Exposure to a chemical for a duration of 15–364 days, as specified in the 

Toxicological Profiles. 

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 that 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 that 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. 
TIN AND TIN COMPOUNDS 374 

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) that 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 OR of greater than 1 is considered to indicate greater risk of disease in the 

exposed group compared to the unexposed group. 

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 dynamic behavior of a material in the body, used to predict 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, whereas the 

physiologically-based model compartments represent real anatomic regions of the body. 

Physiologically Based Pharmacodynamic (PBPD) Model—A type of physiologically based doseresponse model that 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. 

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 
TIN AND TIN COMPOUNDS 375 

10. GLOSSARY 

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) concentration 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. 

Risk—The possibility or chance that some adverse effect will result from a given exposure to a chemical. 
 

TIN AND TIN COMPOUNDS 376 

10. GLOSSARY 

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 group. 

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 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 1 can be used; 

however, a reduced UF of 3 may be used on a case-by-case basis, 3 being the approximate logarithmic 

average of 10 and 1. 

Xenobiotic—Any chemical that is foreign to the biological system. 
TIN AND TIN COMPOUNDS 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. 

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 
TIN AND TIN COMPOUNDS A-2 

APPENDIX A 

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 100-fold 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 F-32, Atlanta, Georgia 30333. 
 

 

 

 

TIN AND TIN COMPOUNDS A-3 

APPENDIX A 

MINIMAL RISK LEVEL WORKSHEET 

Chemical Name: Tin 

CAS Numbers: 7440-31-5 

Date: April 2005 

Profile Status: Final Post-Public Comment 

Route: [ ] Inhalation [X] Oral 

Duration: [ ] Acute [X] Intermediate [ ] Chronic 

Graph Key: 13 

Species: Rat 

Minimal Risk Level: 0.3 [X] mg/kg/day [ ] ppm 

Reference: De Groot AP, Feron VJ, Til HP. 1973. Short-term toxicity studies on some salts and oxides 

of tin in rats. Food Cosmet Toxicol 11:19-30. 

Experimental design: The effect of stannous chloride was studied in male and female Wistar rats 

(10/sex/dose level) for 13 weeks at dietary levels of 0, 300, 1,000, 3,000, and 10,000 ppm. Using a 

conversion dietary factor of 0.05 kg food/kg body weight/day and the molecular weight of 118.69 for tin, 

it can be estimated that the diet provided approximate doses of 0, 9.5, 32, 95, or 315 mg Sn/kg/day. End 

points monitored included: survival, body weight, food intake, hematology (hemoglobin, hematocrit, total 

erythrocytes, total and differential leukocytes), serum chemistry (transaminases, alkaline phosphatase, 

bilirubin), urinalysis, organ weights (nine organs), and gross and microscopic pathology. Tin in the 

standard diet was not determined, but the concentrations of calcium, phosphorus, iron, copper, and zinc 

were known. The concentrations of these minerals were consistent with the concentrations in standard 

rat’s diets, except for the amount of zinc, which was about 50% of that found in the standard diet. 

Effect noted in study and corresponding doses: The highest dietary level (315 mg Sn/kg/day) caused 

reduced food consumption and abdominal distension on week 1. At week 8, loss of body weight occurred 

in males and females, and one male died. At week 9 another three males died and the group was 

discontinued. Rats in the 95 mg/kg/day level showed poor appetite and abdominal distension the first 

2 weeks; this was associated with decreased food consumption, but they kept growing. At termination, no 

significant differences in body weights were seen. Food consumption was low also at 32 mg/kg/day, but 

only on week 1. Hemoglobin concentration was significantly reduced starting at week 4 at 95 and 

315 mg/kg/day (about 12 and 20%, respectively) and only at week 4 in 32 mg/kg/day males (3% 

reduction). Terminal hemoglobin and hematocrit were significantly reduced only in high-dose males 

(6 and 4%, respectively). Tin had no noticeable effect on osmotic resistance of the erythrocytes or on the 

number of reticulocytes. Serum alkaline phosphatase was significantly decreased at termination in both 

sexes but there was no significant effect on transaminases or in bilirubin. Terminal urine samples were 

unremarkable, as were relative organ weights. Rats from the high-dose group which had to be terminated 

early showed distended intestines, slight edema of the pancreas, and grayish-brown livers. There was 

moderate testicular degeneration, severe pancreatic atrophy, spongy white matter in the brain, acute 

bronchopneumonia, enteritis and liver changes characterized by homogeneous appearance of the liver cell 

cytoplasm and mild proliferation of the bile duct epithelium. In the other groups at termination, 

treatment-related effects included bile duct epithelium proliferation and homogeneous cytoplasm at 

95 mg/kg/day. The 95 mg/kg/day dose level is considered a minimal LOAEL based on the unknown 

biological significance of a transient 12% reduction in hemoglobin concentration. 

Dose and end point used for MRL derivation: 32 mg/kg/day; decreased hemoglobin concentration. 

[X] NOAEL [ ] LOAEL 
TIN AND TIN COMPOUNDS A-4 

APPENDIX A 

Uncertainty Factors used in MRL derivation: 

[ ] 10 for use of a LOAEL 

[X] 10 for extrapolation from animals to humans 

[X] 10 for human variability 

Was a conversion factor used from ppm in food or water to a mg/body weight dose? 

Yes. 

If an inhalation study in animals, list conversion factors used in determining human equivalent dose: NA 

Was a conversion used from intermittent to continuous exposure? 

No 

Other additional studies or pertinent information that lend support to this MRL: The effects of the 

administration of stannous chloride, stannous orthophosphate, stannous sulfate, and stannous tartrate at 

the same dietary levels as above in the diet of rats for 4 weeks are in agreement with the data from the 

13-week study (De Groot et al. 1973). The LOAELs for body weight gain, depressed hemoglobin and 

hematocrit values, and liver histopathology at 4 weeks were seen with the 3,000 ppm diet in males. The 

NOAEL was the 1,000 ppm diet. With the orthophosphate and tartrate salts, the differences in 

hemoglobin and hematocrit were not significant with the 3,000 ppm diet, but were significant with the 

10,000 ppm diet. 

Janssen et al. (1985) reported a LOAEL of 7.9 mg/kg/day for significant decreases in hemoglobin in rats 

fed a diet containing stannous chloride for 28 days. However, the standard diet contained only 20% of the 

copper reported for the diet in the De Groot et al. (1973) study. The lower concentrations of these 

minerals may have made the rats in the Jenssen et al. (1985) study more susceptible to the effects of tin on 

hematopoiesis. Transient hemolytic anemia was also reported in rabbits administered 10 mg tin/kg/day 

(as stannous chloride), the only dose level tested, by gavage for 4 months (Chmielnicka et al. 1993). 

However, no information was provided in that study regarding the trace mineral composition of the diet. 

Agency Contact (Chemical Manager): Carolyn Harper, Ph.D. 
 

 

 

 

TIN AND TIN COMPOUNDS A-5 

APPENDIX A 

MINIMAL RISK LEVEL WORKSHEET 

Chemical Name: Dibutyltin dichloride 

CAS Number: 683-18-1 

Date: April 2005 

Profile Status: Final Post-Public Comment 

Route: [ ] Inhalation [X] Oral 

Duration: [ ] Acute [X] Intermediate [ ] Chronic 

Graph Key: 28 

Species: Rat 

Minimal Risk Level: 0.005 [X] mg/kg/day [ ] ppm 

Reference: Seinen W, Vos JG, van Krieken R, et al. 1977b. Toxicity of organotin compounds. III. 

Suppression of thymus-dependent immunity in rats by di-n-butyltindichloride and di-n-octyltindichloride. 

Toxicol Appl Pharmacol 42:213-224. 

Experimental design: Groups of male and female weanling Wistar rats (5–10/group) were fed diets 

containing 0, 50, or 150 ppm of the test material (>98% pure) for 4–6 weeks. Based on a body weight of 

0.2 kg, it can be estimated that these levels provided doses of dibutyltin dichloride of approximately 0, 5, 

and 15 mg/kg/day (EPA 1988). End points examined included body weight and parameters of humoral 

and cellular immune responses. The humoral immune response was assessed by measuring formation of 

antibodies against SRBC and E. coli lipopolysaccharide. Rats were immunized intraperitoneally with 

SRBC 5 days before termination of the experiments. The cellular immune response was assessed by 

examining allograft rejection (rats were grafted at week 7). 

Effects noted in study and corresponding doses: Final body weight after 4 weeks of exposure was not 

significantly altered relative to controls, but it was 28% lower than controls in the high-dose group after 

6 weeks of exposure. Allograft rejection time was significantly delayed in the high-dose group relative to 

controls. In the tests for humoral response, the number of antibody-producing cells per million spleen 

cells was not affected, but the number per whole spleen was significantly decreased in a dose-related 

manner. This response was associated with a decreased hemagglutination titer in the high-dose group. 

The antibody titers against E. coli lipopolysaccharide were slightly but not significantly lower in treated 

groups than in controls. The dose of 5 mg/kg/day is the study LOAEL based on the reduction in 

hemagglutinating antibodies against SRBC. 

Dose and end point used for MRL derivation: 5.0 mg/kg/day; immunological effects. 

[ ] NOAEL [X] LOAEL 

Uncertainty Factors used in MRL derivation: 

[X] 10 for use of a LOAEL 

[X] 10 for extrapolation from animals to humans 

[X] 10 for human variability 

Was a conversion factor used from ppm in food or water to a mg/body weight dose?
 

Yes. A food factor of 0.1 kg food/day/kg body weight was calculated using a body weight of 0.2 kg 

(from study) in an allometric equation (EPA 1988). 

If an inhalation study in animals, list conversion factors used in determining human equivalent dose: NA 
TIN AND TIN COMPOUNDS A-6 

APPENDIX A 

Was a conversion used from intermittent to continuous exposure? 

No 

Other additional studies or pertinent information that lend support to this MRL: Limited additional 

information was available for dibutyltin dichloride from intermediate-duration studies. Gaunt et al. 

(1968) conducted a 90-day dietary general toxicity and histopathology study in rats and found no 

significant effects other than a slight reduction in hemoglobin with the highest dose tested 

(5.7 mg/kg/day); no effect was seen at 3.4 mg/kg/day. Although the Gaunt et al. (1968) study defined a 

NOAEL and, possibly a minimal LOAEL, the immunological alterations reported in the Seinen et al. 

(1977b) study are preferred as basis for the intermediate-duration oral MRL because of the known 

immunotoxic properties of dibutyltins (i.e., Seinen et al. 1977a) and tributyltins (dibutyltin is a metabolite 

of tributyltin; Matsuda et al. 1993; Ueno et al. 1994). In two acute-duration oral studies in rats, serious 

LOAELs were described at or below the 5 mg/kg/day intermediate-duration LOAEL from Seinen et al. 

(1977b). In Ema et al. (1991b), 5 mg/kg/day was a serious developmental LOAEL and in Ema and 

Harazono (2000), 3.8 mg/kg/day was a serious reproductive LOAEL. However, in these two studies, the 

rats were treated with dibutyltin dichloride by gavage in oil, and the bolus administration may have 

contributed to the severity of the effects. 

Agency Contact (Chemical Manager): Carolyn Harper, Ph.D. 
 

 

 

 

TIN AND TIN COMPOUNDS A-7 

APPENDIX A 

MINIMAL RISK LEVEL WORKSHEET 

Chemical Name: Tributyltin oxide 

CAS Number: 56-35-9 

Date: April 2005 

Profile Status: Final Post-Public Comment 

Route: [ ] Inhalation [X] Oral 

Duration: [ ] Acute [X] Intermediate [ ] Chronic 

Graph Key: 66 

Species: Rat 

Minimal Risk Level: 0.0003 [X] mg/kg/day [ ] ppm 

Reference: Vos JG, De Klerk A, Krajnc EI, et al. 1990. Immunotoxicity of bis(tri-n-butyltin)oxide in 

the rat: effects on thymus-dependent immunity and on nonspecific resistance following long-term 

exposure in young versus aged rats. Toxicol Appl Pharmacol 105:144-155. 

Experimental design: Groups of male Wistar rats were fed a diet containing 0, 0.5, 5, or 50 ppm 

tributyltin oxide (95.3% pure) for 4.5–6 months. This diet provided approximately 0, 0.025, 0.25, and 

2.5 mg/kg/day of the tin compound. Parameters of specific resistance evaluated included IgM and IgG 

response to ovalbumin and delayed-type hypersensitivity (DTH) response to ovalbumin and tuberculin 

after 6 months of treatment; resistance to Trichinella spiralis infection after 5.5 months; mitogenic 

response of thymus and spleen cells after 4.5 months; and surface marker analysis of mesenteric lymph 

nodes after 6 months. Parameters of nonspecific resistance examined included clearance of Listeria 

monocytogenes from the spleen after injection at 5 months and natural cell-mediated cytotoxicity of 

spleen and peritoneal cells after 4.5 months. 

Effects noted in study and corresponding doses: Neither body weight nor spleen weight were 

significantly altered after 4.5 months of treatment, but thymus weight was reduced by 17% relative to 

controls in the high-dose group. Neither the IgM nor IgG response to ovalbumin and T. spiralis were 

altered after 5.5 months of exposure. The immunoglobulin E (IgE) responses to T. spiralis, as determined 

by the passive cutaneous anaphylaxis reaction, were suppressed in a dose-related manner (significant in 

the mid- and high-dose groups). The DTH reactions to ovalbumin and tuberculin were not significantly 

altered after 6 months of dosing. There was an increase in the number of larvae T. spiralis in muscle after 

infection in the mid- and high-dose groups after 5.5 months of exposure to the tin compound. No 

significant effect was observed on the response of spleen cells to T- and B-mitogens after 4.5 months. 

The cell surface marker analysis of mesenteric lymph node cells showed a reduction in the relative count 

of T-lymphocytes and an increase in the percentage of B-lymphocytes in the mid- and high-dose groups 

after 6 months of treatment. The in vivo clearance of L. monocytogenes was impaired in the high-dose 

group after 5 months of treatment. Treatment with tributyltin oxide did not induce a consistent effect on 

the natural killer cell activity of spleen and peritoneal cells after 4.5 months of exposure (decreased in the 

low- and high-dose groups, and increased in the mid-dose group). Based on the depression of IgE titers 

and increased T. spiralis in muscle after 5.5 months of exposure to tributyltin oxide, the study LOAEL is 

0.25 mg/kg/day and the NOAEL is 0.025 mg/kg/day. 

Dose and end point used for MRL derivation: 0.025 mg/kg/day; immunological effects. 

[X] NOAEL [ ] LOAEL 
 

TIN AND TIN COMPOUNDS A-8 

APPENDIX A 

Uncertainty Factors used in MRL derivation: 

[ ] 10 for use of a LOAEL 

[X] 10 for extrapolation from animals to humans 

[X] 10 for human variability 

Was a conversion factor used from ppm in food or water to a mg/body weight dose? 

Yes, conversions were done by the study authors. 

If an inhalation study in animals, list conversion factors used in determining human equivalent dose: NA 

Was a conversion used from intermittent to continuous exposure? 

No 

Other additional studies or pertinent information that lend support to this MRL: Numerous studies in 

animals have demonstrated that the main target for some alkyltin compounds, tributyltin among them, is 

the immune system, particularly the thymus (Boyer 1989; Seinen et al. 1977a, 1977b; Snoeij et al. 1985). 

Therefore, it is expected that additional intermediate-duration studies, which did not focus on the immune 

system, identified higher NOAELs. For example, a 4-week dietary study with tributyltin oxide in rats 

observed slight hematological abnormalities at 0.25 mg/kg/day and hepatic and body weight NOAELs at 

1 mg/kg/day (Krajnc et al. 1984). That same study found a 17% in thymus weight at 1 mg/kg/day and a 

35% decrease at 4 mg/kg/day. An additional study with tributyltin oxide reported reduced natural killer 

cell activity in rats at 1 mg/kg/day following 6 weeks of treatment (Van Loveren et al. 1990). In yet 

another rat study, Verdier et al. (1991) reported slight impairment in host resistance to L. monocytogenes 

following exposure to tributyltin oxide for 28 days at 5 mg/kg/day, but not at 1 mg/kg/day. 

The NOAEL of 0.025 mg/kg/day of Vos et al. (1990) is supported by recent developmental studies with 

tributyltin chloride that evaluated systemic and immunologic parameters in the offspring of rats exposed 

to tributyltin chloride in utero (Gds 8-21), through the mother’s milk, and directly as young adults until 

the age of 90 days (Cooke et al. 2004; Tryphonas et al. 2004). The doses tested were 0, 0.025, 0.25, and 

2.5 mg/kg/day. Neither body weights nor food consumption was affected in the dams. No effects were 

observed on litter size, pup weight at birth, sex ratio, or survival until weaning. Growth of the treated 

pups after weaning was slightly reduced (<10%) relative to controls and analysis of food consumption 

and weight gain showed that male pups converted feed into weight gain less effectively than females. No 

effects were seen on the weights of pup's brain, kidney or adrenals, but there was a decrease in absolute 

and relative liver weight in 60-day-old females at 0.025 and 2.5 mg/kg/day, a decrease in absolute and 

relative liver weight in 90-day-old males at 2.5 mg/kg/day, decrease in absolute spleen weight in 30-dayold males at 2.5 mg/kg/day and in relative spleen weight in 60-day-old females at 2.5 mg/kg/day, and a 

decrease in relative thymus weight in 60-day-old females at 0.25 and 2.5 mg/kg/day and in absolute 

thymus weight in 30-day-old males at 2.5 mg/kg/day. No consistent treatment-related gross or 

microscopic lesions were observed in dams and pups. Clinical chemistry changes of potential biological 

importance included a decrease in serum amylase in 90-day-old males at 0.25 and 2.5 mg/kg/day and 

decreased T4, also in 90-day-old males at 2.5 mg/kg/day. Based on the changes in pup's organ weights 

and in clinical chemistry parameters, the 0.25 mg/kg/day dose is a LOAEL and 0.025 mg/kg/day a 

NOAEL. The reduced weight gain of the pups is not considered adverse because the difference with 

controls was less than 10%. 

In the study of immunological parameters (Tryphonas et al. 2004), the only significant change in serum 

immunoglobulin levels that appeared dose-related was an increase in IgG at 0.25 and 2.5 mg/kg/day in 

90-day-old males. Flow cytometric analysis of splenocytes showed a significant increase mean percent 

and absolute NK cell numbers in high-dose 30-day-old males and females, a decrease in the percentage, 
TIN AND TIN COMPOUNDS A-9 

APPENDIX A 

but not in absolute numbers of CD4+8+ T cells in 60-day-old females, and an increase in the percentage 

of NK cells in 90-day-old males. The anti-SRBC IgM response was not affected by exposure to 

tributyltin. No significant alterations were observed in the lymphoproliferative activity of splenocytes in 

response to mitogen stimulation. The delayed-type hypersensitivity response (DTH) was not affected in 

60-day-old females, but 90-day-old males showed a significant trend toward a decrease in DTH response 

with increasing doses of tributyltin. The assays for L. monocytogenes infectivity and NK cell activity did 

not give dose-related responses. Cytokine levels in serum were not affected. Gross examination of 

lymphoid tissues was unremarkable. The most consistent histological finding was mild to moderate 

cortical atrophy of the thymus, characterized by decreased numbers of cortical lymphocytes at 

2.5 mg/kg/day at all ages. 

Agency Contact (Chemical Manager): Carolyn Harper, Ph.D. 
 

 

 

 

TIN AND TIN COMPOUNDS A-10 

APPENDIX A 

MINIMAL RISK LEVEL WORKSHEET 

Chemical Name: Tributyltin oxide 

CAS Number: 56-35-9 

Date: April 2005 

Profile Status: Final Post-Public Comment 

Route: [ ] Inhalation [X] Oral 

Duration: [ ] Acute [ ] Intermediate [X] Chronic 

Graph Key: 79 

Species: Rat 

Minimal Risk Level: 0.0003 [X] mg/kg/day [ ] ppm 

Reference: Vos JG, De Klerk A, Krajnc EI, et al. 1990. Immunotoxicity of bis(tri-n-butyltin)oxide in 

the rat: Effects on thymus-dependent immunity and on nonspecific resistance following long-term 

exposure in young versus aged rats. Toxicol Appl Pharmacol 105:144-155. 

Experimental design: Groups of male Wistar rats were fed a diet containing 0, 0.5, 5, or 50 ppm 

tributyltin oxide (95.3% pure) for 18 months. This diet provided approximately 0, 0.025, 0.25, and 

2.5 mg/kg/day of the test material. Parameters of specific resistance evaluated included IgM and IgG 

response to sheep red blood cells (SRBC) after 16 months; IgM and IgG response to ovalbumin and the 

delayed-type hypersensitivity (DTH) response to ovalbumin and tuberculin after 15 months of treatment; 

resistance to T. spiralis infection after 16.5 months; mitogenic response of thymus and spleen cells after 

16.5 months; and surface marker analysis of mesenteric lymph nodes after 18 months. Parameters of 

nonspecific resistance examined included clearance of L. monocytogenes from the spleen after injection at 

17 months and natural cell-mediated cytotoxicity of spleen and peritoneal cells after 16 months. 

Effects noted in study and corresponding doses: No information was provided regarding body weight or 

weight of the thymus and spleen at termination. Exposure to tributyltin oxide did not affect the primary 

IgM or the secondary response to SRBC after 16 months of dosing. Neither the IgM nor IgG response to 

ovalbumin and T. spiralis were altered after 15 months of treatment, but the IgE responses to T. spiralis, 

as determined by the passive cutaneous anaphylaxis reaction, was suppressed in a dose-related manner 

(significant in the mid- and high-dose groups). The DTH reactions to ovalbumin and tuberculin were not 

significantly altered after 16 months of dosing. There was an increase in the number of larvae T. spiralis 

in muscle after infection in the mid- and high-dose groups after 16.5 months of exposure to the test 

material. No significant effect was observed on the response of spleen cells to T- and B-mitogens after 

16 months. The cell surface marker analysis of mesenteric lymph node cells showed a reduction in the 

relative count of T-lymphocytes and an increase in the percentage of B-lymphocytes in the mid- and highdose groups after 18 months of treatment. The in vivo clearance of L. monocytogenes was impaired in the 

high-dose group after 17 months of treatment. Treatment with tributyltin oxide for 16 months 

significantly reduced the natural killer cell activity of spleen and peritoneal cells, but there was no doseresponse relationship. Based on the depression of IgE titers and increased T. spiralis in muscle after 

16.5 months of exposure to tributyltin oxide, the study LOAEL is 0.25 mg/kg/day and the NOAEL is 

0.025 mg/kg/day. 

Dose and end point used for MRL derivation: 0.025 mg/kg/day; immunological effects. 

[X] NOAEL [ ] LOAEL 
TIN AND TIN COMPOUNDS A-11 

APPENDIX A 

Uncertainty Factors used in MRL derivation: 

[ ] 10 for use of a LOAEL 

[X] 10 for extrapolation from animals to humans 

[X] 10 for human variability 

Was a conversion factor used from ppm in food or water to a mg/body weight dose? 

Yes, conversions were done by the study authors. 

If an inhalation study in animals, list conversion factors used in determining human equivalent dose: NA 

Was a conversion used from intermittent to continuous exposure? 

No 

Other additional studies or pertinent information that lend support to this MRL: The findings from the 

intermediate-duration portion of the Vos et al. (1990) study support the longer-term observations. A 

2-year bioassay with tributyltin oxide in rats described hepatic, renal, endocrine, and body weight effects 

with a dose level of 2.1 mg/kg/day and NOAELs for these effects are approximately 0.2 mg/kg/day 

(Wester et al. 1990). In that study there also were changes in immunoglobulin levels at 2.1 mg/kg/day 

throughout the study, namely: increase in IgA after 12 and 24 months, decrease in IgG in females after 

3 and 13 months, and increase in IgM after 3, 12, and 24 months. No additional chronic-duration studies 

were located for tributyltin oxide. 

Agency Contact (Chemical Manager): Carolyn Harper, Ph.D. 

TIN AND TIN COMPOUNDS 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 that they appear within the Discussion of Health Effects 

by Route of Exposure section, by route (inhalation, oral, and 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. 

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. 

Interpretation of Minimal Risk Levels 

Where sufficient toxicologic information is available, ATSDR has derived 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. 
 

TIN AND TIN COMPOUNDS B-2 

APPENDIX B 

MRLs 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 that the Environmental Protection Agency (EPA) 

provides (Barnes and Dourson 1988) to determine reference doses (RfDs) for lifetime exposure. 

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 no-observed-adverse-effect 

level (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 levels of significant exposure 

(LSE) tables. 

Chapter 3 

Health Effects 

Tables and Figures for Levels of Significant Exposure (LSE) 

Tables and figures 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, 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 NOAELs, LOAELs, or Cancer Effect Levels (CELs). 

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. 
TIN AND TIN COMPOUNDS B-3 

APPENDIX B 

LEGEND 

See Sample LSE Table 3-1 (page B-6) 

(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. Typically 

when sufficient data exist, 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 Tables 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 two "18r" data points in sample 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 

regimens 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 “Chemical x” via inhalation 

for 6 hours/day, 5 days/week, for 13 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, one systemic effect (respiratory) was 

investigated. 

(8)	 NOAEL. A 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"). 
TIN AND TIN COMPOUNDS B-4 

APPENDIX B 

(9)	 LOAEL. A 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 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 that the NOAEL of 3 ppm in key number 18 was used to 

derive an MRL of 0.005 ppm. 

LEGEND 

See Sample Figure 3-1 (page B-7) 

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 acute and intermediate 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). 

(17) CEL. Key number 38m is one of three studies for which CELs were derived. The diamond 

symbol refers to a CEL for the test species-mouse. The number 38 corresponds to the entry in the 

LSE table. 
TIN AND TIN COMPOUNDS B-5 

APPENDIX B 

(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. 
B-6 

3 

4 

TIN AND TIN COMPOUNDS 

APPENDIX B 

SAMPLE
 

1 o Table 3-1. Levels of Significant Exposure to [Chemical x] – Inhalation 

Key to 

figurea 

Exposure 

frequency/ 

Species duration System 

NOAEL 

(ppm) 

LOAEL (effect) 

Less serious 

(ppm) 

Serious (ppm) 

Reference 

2 o
 

o
 

o
 

INTERMEDIATE EXPOSURE
 

5 6 7 8 9 10 

Systemic p p p p p p

18 Rat 13 wk Resp 3b 10 (hyperplasia) 

5 d/wk 

6 hr/d 

Nitschke et al. 1981 

CHRONIC EXPOSURE 

Cancer 11 

p

38 Rat 18 mo 20 (CEL, multiple Wong et al. 1982 

5 d/wk 

7 hr/d 

organs) 

39 Rat 89–104 wk 10 (CEL, lung tumors, NTP 1982 

5 d/wk 

6 hr/d 

nasal tumors) 

40 Mouse 79–103 wk 10 (CEL, lung tumors, NTP 1982 

5 d/wk hemangiosarcomas) 

6 hr/d 

12 o	 a

 The number corresponds to entries in Figure 3-1. 

b

 Used to derive an intermediate inhalation Minimal Risk Level (MRL) of 5x10-3 ppm; dose adjusted for intermittent exposure and divided 

by an uncertainty factor of 100 (10 for extrapolation from animal to humans, 10 for human variability). 
B-7 TIN AND TIN COMPOUNDS 

APPENDIX B 

TIN AND TIN COMPOUNDS C-1 

APPENDIX C. ACRONYMS, ABBREVIATIONS, AND SYMBOLS 

ACGIH American Conference of Governmental Industrial Hygienists 

ACOEM American College of Occupational and Environmental Medicine 

ADI acceptable daily intake 

ADME absorption, distribution, metabolism, and excretion 

AED atomic emission detection 

AFID alkali flame ionization detector 

AFOSH Air Force Office of Safety and Health 

ALT alanine aminotransferase 

AML acute myeloid leukemia 

AOAC Association of Official Analytical Chemists 

AOEC Association of Occupational and Environmental Clinics 

AP alkaline phosphatase 

APHA American Public Health Association 

AST aspartate aminotransferase 

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 

BMD benchmark dose 

BMR benchmark response 

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 
 

TIN AND TIN COMPOUNDS 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 

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 

kkg metric ton 

Koc organic carbon partition coefficient 

Kow octanol-water partition coefficient 

L liter 

LC liquid chromatography 

LC50 lethal concentration, 50% kill 

LCLo lethal concentration, low 

LD50 lethal dose, 50% kill 

LDLo lethal dose, low 

LDH lactic dehydrogenase 

LH luteinizing hormone 

LOAEL lowest-observed-adverse-effect level 

LSE Levels of Significant Exposure 

LT50 lethal time, 50% kill 

m meter 

MA trans,trans-muconic acid 

MAL maximum allowable level 

mCi millicurie 

MCL maximum contaminant level 
TIN AND TIN COMPOUNDS C-3 

APPENDIX C 

MCLG maximum contaminant level goal 

MF modifying factor 

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 

NHANES National Health and Nutrition Examination Survey 

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 

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 

OPPT Office of Pollution Prevention and Toxics, EPA 

OPPTS Office of Prevention, Pesticides and Toxic Substances, EPA 

OR odds ratio 

OSHA Occupational Safety and Health Administration 

OSW Office of Solid Waste, EPA 

OTS Office of Toxic Substances 

OW Office of Water 
TIN AND TIN COMPOUNDS C-4 

APPENDIX C 

OWRS Office of Water Regulations and Standards, EPA 

PAH polycyclic aromatic hydrocarbon 

PBPD physiologically based pharmacodynamic 

PBPK physiologically based pharmacokinetic 

PCE polychromatic erythrocytes 

PEL permissible exposure limit 

pg picogram 

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 

REL recommended exposure level/limit 

RfC reference concentration 

RfD reference dose 

RNA ribonucleic acid 

RQ reportable quantity 

RTECS Registry of Toxic Effects of Chemical Substances 

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 

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 

TWA time-weighted average 

UF uncertainty factor 

U.S. United States 

USDA United States Department of Agriculture 

USGS United States Geological Survey 

VOC volatile organic compound 

WBC white blood cell 

WHO World Health Organization 
TIN AND TIN COMPOUNDS C-5 

APPENDIX C 

> greater than  greater than or equal to 

= equal to 

< less than  less than or equal to 

% percent Į alpha ȕ beta Ȗ gamma į delta μm micrometer μg microgram q1

* cancer slope factor 

– negative 

+ positive 

(+) weakly positive result 

(–) weakly negative result 

TIN AND TIN COMPOUNDS D-1 

APPENDIX D. INDEX 

AAS .......................................................................................................... 291, 292, 293, 294, 295, 296, 297 

absorbed dose............................................................................................................................................204 

active transport..........................................................................................................................................205 

adipose tissue ............................................................................................................................ 176, 276, 288 

adrenal gland.............................................................................................................................................151 

adrenals ............................................................................................................................................. 127, 147 

adsorbed ............................................................................................................................................ 252, 256 

adsorption.................................................................................................................. 255, 256, 257, 259, 291 

aerobic.......................................................................................................................................................290 

alanine aminotransferase (see ALT) .........................................................................................................123 

ALT................................................................................................................................................... 123, 155 

ambient air ................................................................................................................................................261 

anaerobic........................................................................................................................................... 259, 290 

anemia....................................................................................................................... 5, 13, 16, 118, 206, 207 

antiandrogenic...........................................................................................................................................196 

antifouling agent .......................................................................................................................................247 

aspartate aminotransferase (see AST).......................................................................................................123 

AST................................................................................................................................................... 123, 155 

atomic absorption spectroscopy (see AAS) ...................................................................... 291, 292, 294, 296
 

bioavailability ........................................................................................................................... 215, 257, 287 

bioconcentration................................................................................................................................ 256, 257 

bioconcentration factor .............................................................................................................................256 

biodegradation................................................................................................................................... 252, 260 

biomarker .......................................................................................................................................... 203, 204 

biomarkers ................................................................................................................ 203, 204, 220, 223, 291 

blood cell count.........................................................................................................................................119 

body weight effects ...................................................................................................................................130 

breast milk............................................................................................................. 7, 175, 202, 284, 285, 289 

cancer .................................................................................... 5, 6, 13, 36, 149, 150, 158, 196, 201, 215, 224 

carcinogen.................................................................................................................................................307 

carcinogenic ................................................................................ 13, 14, 16, 23, 24, 150, 151, 152, 215, 301 

carcinogenicity........................................................................................ 6, 13, 151, 152, 158, 215, 301, 307 

carcinomas ........................................................................................................................................ 149, 215 

cardiovascular ............................................................................................................................. 30, 115, 155 

cardiovascular effects................................................................................................................................115 

chromosomal aberrations .................................................................................................................. 161, 167 

clearance ....................................................................................................................... 21, 22, 134, 185, 307 

cleft palate................................................................................................................................... 15, 145, 148 

crustaceans .................................................................................................................. 12, 271, 275, 276, 283 

death........................................................................................ 15, 23, 25, 112, 136, 152, 193, 212, 276, 278 

deoxyribonucleic acid (see DNA)..................................................................................................... 162, 168 

dermal effects.............................................................................................................................. 33, 129, 156 

desorption.......................................................................................................................................... 257, 295 

DNA.................................................................................................................. 161, 162, 167, 168, 193, 203 

dopamine........................................................................................................................................... 139, 147 

elimination half-time................................................................................................................. 182, 183, 185 

elimination rate .........................................................................................................................................221 

endocrine..................................................... 15, 126, 127, 128, 195, 196, 197, 199, 202, 214, 217, 218, 223 
TIN AND TIN COMPOUNDS D-2 

APPENDIX D 

endocrine effects .......................................................................................................................................126 

erythema....................................................................................................................................................156 

estrogen receptor.......................................................................................................................................196 

estrogenic ..................................................................................................................................................196 

fetus....................................................................................................................... 6, 174, 196, 200, 217, 223 

fractional absorption .................................................................................................................................169 

FSH ................................................................................................................................... 127, 197, 198, 206 

gas chromatography (see GC)................................................................................................... 291, 294, 296 

gastrointestinal effects .................................................................................................... 5, 31, 116, 117, 223 

GC..................................................................................................................... 291, 293, 294, 295, 296, 297 

general population................................................................................. 12, 15, 173, 203, 213, 220, 282, 285 

genotoxic............................................................................................................... 13, 23, 161, 167, 212, 216 

genotoxicity....................................................................................................................................... 161, 216 

groundwater .............................................................................................................. 249, 253, 254, 292, 305 

half-life...................................................................................................................................... 203, 257, 259 

hematological effects .................................................................................. 13, 14, 16, 17, 32, 118, 119, 301 

hepatic effects ............................................................................................. 32, 120, 121, 122, 125, 155, 213 

high performance liquid chromatography (see HPLC).............................................................................294
 

hippocampus ............................................................... 15, 136, 138, 147, 159, 177, 191, 192, 201, 219, 225 

HPLC ................................................................................................................................ 291, 293, 294, 295 

hydrolysis.......................................................................................................................................... 252, 260 

ICP .................................................................................................................... 292, 293, 294, 295, 296, 297 

immune system ....................................................................................................................... 5, 19, 205, 218 

immunological ...................... 14, 19, 21, 22, 23, 34, 131, 132, 135, 147, 151, 157, 201, 213, 214, 218, 301 

immunological effects......................................................... 14, 19, 21, 22, 34, 131, 132, 135, 201, 213, 301 

inductively coupled plasma (see ICP)............................................................................... 291, 292, 294, 296 

Kow ............................................................................................................................................................257 

LD50........................................................................................................................................... 113, 114, 152 

leukemia....................................................................................................................................................161 

limbic system ...................................................................................................................................... 15, 191 

lymphoreticular................................................................................................................................. 132, 157 

mass spectrometry (see MS) ............................................................................................. 291, 292, 294, 296 

methylation ............................................................................................................................... 259, 260, 287 

micronuclei ....................................................................................................................................... 161, 167 

milk ................................................................................... 147, 202, 208, 218, 222, 223, 275, 276, 285, 289 

MS............................................................................................................. 291, 292, 293, 294, 295, 296, 297 

musculoskeletal effects ....................................................................................................................... 30, 120 

myelin ......................................................................................................................... 14, 137, 189, 190, 193 

neonatal..................................................................................................................... 137, 170, 175, 176, 199 

neurobehavioral................................................................................................................... 34, 196, 212, 220 

neurochemical...........................................................................................................................................202 

neurodevelopmental.......................................................................................................................... 146, 202 

norepinephrine ..........................................................................................................................................192 

nuclear.......................................................................................................................................................225 

ocular effects....................................................................................................... 33, 114, 129, 152, 157, 213 

partition coefficients .................................................................................................................................257 

pharmacodynamic.....................................................................................................................................184 

pharmacokinetic.................................................................................. 13, 184, 185, 186, 200, 202, 219, 223 

photolysis ..................................................................................................................................................260 

pKa.................................................................................................................................................... 258, 259 

placenta ......................................................................................................................... 6, 199, 202, 217, 223 
TIN AND TIN COMPOUNDS D-3 

APPENDIX D 

pyriform cortex ........................................................................................................................... 15, 138, 139 

renal effects......................................................................................................... 32, 124, 125, 126, 155, 214 

retention ...................................... 16, 123, 146, 170, 171, 178, 180, 189, 198, 205, 206, 246, 282, 304, 307 

salivation...................................................................................................................................................139 

solubility ........................................................................................................................................... 256, 286 

spermatogonia................................................................................................................................... 142, 197 

T3...................................................................................................................................................... 128, 196 

T4...................................................................................................................................... 127, 147, 196, 197 

thymocytes .................................................................................................................................. 14, 193, 194 

thyroid....................................................................................................... 126, 127, 128, 149, 193, 196, 197 

thyroxine ............................................................................................................................................. 21, 127 

toxicokinetic................................................................................................................ 23, 194, 220, 221, 222 

tremors ...................................................................................................................................... 113, 138, 139 

triiodothyronine.........................................................................................................................................196 

TSH................................................................................................................................................... 127, 197 

tumors ....................................................................................................................... 149, 150, 151, 194, 215 

UV..................................................................................................................................................... 252, 259 

vapor pressure ........................................................................................................... 252, 254, 256, 258, 286 

volatilization .............................................................................................................................................254 

weanling......................................................................................................................................................19