TOXICOLOGICAL PROFILE FOR 

1,1,2,2-TETRACHLOROETHANE 


 


 


 


 

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
 

Public Health Service
 

Agency for Toxic Substances and Disease Registry
 

September 2008 
 

1,1,2,2-TETRACHLOROETHANE 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. 
 

 

1,1,2,2-TETRACHLOROETHANE iii 

UPDATE STATEMENT 

A Toxicological Profile for 1,1,2,2-tetrachloroethane, Draft for Public Comment, was released in 

September 2006. 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 and Environmental Medicine/Applied Toxicology Branch
 

1600 Clifton Road NE
 

Mailstop F-32
 

Atlanta, Georgia 30333
 
1,1,2,2-TETRACHLOROETHANE iv 

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1,1,2,2-TETRACHLOROETHANE v 

FOREWORD 

This toxicological profile is prepared in accordance with guidelines developed by the Agency for Toxic 

Substances and Disease Registry (ATSDR) and the Environmental Protection Agency (EPA). The 

original guidelines were published in the Federal Register on April 17, 1987. Each profile will be revised 

and republished as necessary. 

The ATSDR toxicological profile succinctly characterizes the toxicologic and adverse health effects 

information for the hazardous substance described therein. Each peer-reviewed profile identifies and 

reviews the key literature that describes a hazardous substance’s toxicologic properties. Other pertinent 

literature is also presented, but is described in less detail than the key studies. The profile is not intended 

to be an exhaustive document; however, more comprehensive sources of specialty information are 

referenced. 

The focus of the profiles is on health and toxicologic information; therefore, each toxicological profile 

begins with a public health statement that describes, in nontechnical language, a substance’s relevant 

toxicological properties. Following the public health statement is information concerning levels of 

significant human exposure and, where known, significant health effects. The adequacy of information to 

determine a substance’s health effects is described in a health effects summary. Data needs that are of 

significance to protection of public health are identified by ATSDR and EPA. 

Each profile includes the following: 

(A) The examination, summary, and interpretation of available toxicologic information and 

epidemiologic evaluations on a hazardous substance to ascertain the levels of significant human 

exposure for the substance and the associated acute, subacute, and chronic health effects; 

(B) A determination of whether adequate information on the health effects of each substance 

is available or in the process of development to determine levels of exposure that present a 

significant risk to human health of acute, subacute, and chronic health effects; and 

(C) Where appropriate, identification of toxicologic testing needed to identify the types or 

levels of exposure that may present significant risk of adverse health effects in humans. 

The principal audiences for the toxicological profiles are health professionals at the Federal, State, and 

local levels; interested private sector organizations and groups; and members of the public. 

This profile reflects ATSDR’s assessment of all relevant toxicologic testing and information that has been 

peer-reviewed. Staff of the Centers for Disease Control and Prevention and other Federal scientists have 

also reviewed the profile. In addition, this profile has been peer-reviewed by a nongovernmental panel 
 

 

 

 

1,1,2,2-TETRACHLOROETHANE vi 

and was made available for public review. Final responsibility for the contents and views expressed in 

this toxicological profile resides with ATSDR. 

Howard Frumkin M.D., Dr.P.H. Julie Louise Gerberding, M.D., M.P.H. 

Director Administrator 

National Center for Environmental Health/ Agency for Toxic Substances and 

Agency for Toxic Substances and Disease Registry 

Disease Registry 

*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 December 7, 2005 (70 FR 72840). For prior 

versions of the list of substances, see Federal Register notices dated 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); February 28, 1994 (59 FR 9486); 

April 29, 1996 (61 FR 18744); November 17, 1997 (62 FR 61332); October 21, 1999(64 FR 56792); 

October 25, 2001 (66 FR 54014) and November 7, 2003 (68 FR 63098). Section 104(i)(3) of CERCLA, 

as amended, directs the Administrator of ATSDR to prepare a toxicological profile for each substance on 

the list. 
 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 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: 1-800-CDC-INFO (800-232-4636) Fax: (770) 488-4178 

1-888-232-6348 (TTY) 

E-mail: cdcinfo@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 
 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE viii 

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

Toxicity; and numerous chemical-specific case studies. 

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, 25 Northwest Point Boulevard, Suite 700, Elk 

Grove Village, IL 60007-1030 • Phone: 847-818-1800 • FAX: 847-818-9266. 
 

1,1,2,2-TETRACHLOROETHANE ix 

CONTRIBUTORS 

CHEMICAL MANAGER(S)/AUTHOR(S): 

Jessilynn Taylor, M.S.
 

Henry Abadin, M.S.P.H.
 

Eugene Demchuk, Ph.D.
 

ATSDR, Division of Toxicology and Environmental Medicine, Atlanta, GA
 

Stephen Bosch, B.S.
 

David Wohlers, Ph.D.
 

Daniel Plewak, B.S.
 

Syracuse Research Corporation, North Syracuse, NY
 

THE PROFILE HAS UNDERGONE THE FOLLOWING ATSDR INTERNAL REVIEWS: 

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

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

end points. 

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

substance-specific Minimal Risk Levels (MRLs), reviews the health effects database of each 

profile, and makes recommendations for derivation of MRLs. 

3.	 Data Needs Review. The Applied Toxicology 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. 
1,1,2,2-TETRACHLOROETHANE x 

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1,1,2,2-TETRACHLOROETHANE xi 

PEER REVIEW
 

A peer review panel was assembled for 1,1,2,2-tetrachloroethane. The panel consisted of the following 

members: 

1.	 Paul C. Chrostowski, Ph.D., Principal, CPF Associates, Inc., Takoma Park, Maryland; 

2.	 Jeffrey Fisher, Ph.D., Department Head and Professor, Department of Environmental Health 

Sciences, College of Public Health, University of Georgia, Athens, Georgia; and 

3.	 Gary Ginsberg, Ph.D., Consultant in Environmental Toxicology and Risk Assessment, West 

Hartford, Connecticut. 

These experts collectively have knowledge of 1,1,2,2-tetrachloroethane '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. 
1,1,2,2-TETRACHLOROETHANE xii 

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1,1,2,2-TETRACHLOROETHANE 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 IS 1,1,2,2-TETRACHLOROETHANE? .........................................................................2
 

1.2 WHAT HAPPENS TO 1,1,2,2-TETRACHLOROETHANE WHEN IT ENTERS THE
 

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

1.3 HOW MIGHT I BE EXPOSED TO 1,1,2,2-TETRACHLOROETHANE?.................................3
 

1.4 HOW CAN 1,1,2,2-TETRACHLOROETHANE ENTER AND LEAVE MY BODY?..............3
 

1.5 HOW CAN 1,1,2,2-TETRACHLOROETHANE AFFECT MY HEALTH?...............................4
 

1.6 HOW CAN 1,1,2,2-TETRACHLOROETHANE AFFECT CHILDREN? ..................................5
 

1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO 

1,1,2,2-TETRACHLOROETHANE?...........................................................................................5
 

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

1,1,2,2-TETRACHLOROETHANE?...........................................................................................6
 

1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO 

PROTECT HUMAN HEALTH?..................................................................................................6
 

1.10 WHERE CAN I GET MORE INFORMATION? ........................................................................7
 

2. RELEVANCE TO PUBLIC HEALTH ...................................................................................................9
 

2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO 1,1,2,2-TETRACHLOROETHANE IN THE UNITED STATES.........................................................................................9
 

2.2 SUMMARY OF HEALTH EFFECTS.......................................................................................10
 

2.3 MINIMAL RISK LEVELS (MRLs) ..........................................................................................14
 

3. HEALTH EFFECTS..............................................................................................................................21
 

3.1 INTRODUCTION......................................................................................................................21
 

3.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE.................................... 21
 

3.2.1 Inhalation Exposure ..............................................................................................................22
 

3.2.1.1 Death ............................................................................................................................22
 

3.2.1.2 Systemic Effects...........................................................................................................23
 

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

3.2.1.4 Neurological Effects.....................................................................................................35
 

3.2.1.5 Reproductive Effects....................................................................................................36
 

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

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

3.2.2 Oral Exposure........................................................................................................................38
 

3.2.2.1 Death ............................................................................................................................38
 

3.2.2.2 Systemic Effects...........................................................................................................39
 

3.2.2.3 Immunological and Lymphoreticular Effects...............................................................60
 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE xiv 

3.2.2.4 Neurological Effects.....................................................................................................61
 

3.2.2.5 Reproductive Effects....................................................................................................61
 

3.2.2.6 Developmental Effects .................................................................................................62
 

3.2.2.7 Cancer...........................................................................................................................62
 

3.2.3 Dermal Exposure...................................................................................................................63
 

3.2.3.1 Death ............................................................................................................................63
 

3.2.3.2 Systemic Effects...........................................................................................................64
 

3.2.3.3 Immunological and Lymphoreticular Effects...............................................................64
 

3.2.3.4 Neurological Effects.....................................................................................................65
 

3.2.3.5 Reproductive Effects....................................................................................................65
 

3.2.3.6 Developmental Effects .................................................................................................65
 

3.2.3.7 Cancer...........................................................................................................................65
 

3.3 GENOTOXICITY ......................................................................................................................65
 

3.4 TOXICOKINETICS...................................................................................................................69
 

3.4.1 Absorption.............................................................................................................................69
 

3.4.1.1 Inhalation Exposure......................................................................................................69
 

3.4.1.2 Oral Exposure...............................................................................................................70
 

3.4.1.3 Dermal Exposure..........................................................................................................71
 

3.4.2 Distribution ...........................................................................................................................71
 

3.4.3 Metabolism............................................................................................................................72
 

3.4.4 Elimination and Excretion.....................................................................................................75
 

3.4.4.1 Inhalation Exposure......................................................................................................76
 

3.4.4.2 Oral Exposure...............................................................................................................77
 

3.4.4.3 Dermal Exposure..........................................................................................................77
 

3.4.4.4 Other Routes of Exposure ............................................................................................77
 

3.4.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models.............78
 

3.5 MECHANISMS OF ACTION ...................................................................................................79
 

3.5.1 Pharmacokinetic Mechanisms...............................................................................................79
 

3.5.2 Mechanisms of Toxicity........................................................................................................81
 

3.5.3 Animal-to-Human Extrapolations.........................................................................................84
 

3.6 TOXICITIES MEDIATED THROUGH THE NEUROENDOCRINE AXIS ...........................85
 

3.7 CHILDREN’S SUSCEPTIBILITY............................................................................................86
 

3.8 BIOMARKERS OF EXPOSURE AND EFFECT .....................................................................88
 

3.8.1 Biomarkers Used to Identify or Quantify Exposure to 1,1,2,2-Tetrachloroethane ...............89
 

3.8.2 Biomarkers Used to Characterize Effects Caused by 1,1,2,2-Tetrachloroethane .................89
 

3.9 INTERACTIONS WITH OTHER CHEMICALS .....................................................................90
 

3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE................................................90
 

3.11 METHODS FOR REDUCING TOXIC EFFECTS....................................................................91
 

3.11.1 Reducing Peak Absorption Following Exposure..............................................................92
 

3.11.2 Reducing Body Burden.....................................................................................................92
 

3.11.3 Interfering with the Mechanism of Action for Toxic Effects ...........................................93
 

3.12 ADEQUACY OF THE DATABASE.........................................................................................93
 

3.12.1 Existing Information on Health Effects of 1,1,2,2-Tetrachloroethane..............................94
 

3.12.2 Identification of Data Needs .............................................................................................96
 

3.12.3 Ongoing Studies..............................................................................................................107
 

4. CHEMICAL AND PHYSICAL INFORMATION..............................................................................109
 

4.1 CHEMICAL IDENTITY..........................................................................................................109
 

4.2 PHYSICAL AND CHEMICAL PROPERTIES.......................................................................109
 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE xv 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL..........................................................113
 

5.1 PRODUCTION ........................................................................................................................113
 

5.2 IMPORT/EXPORT ..................................................................................................................116
 

5.3 USE...........................................................................................................................................116
 

5.4 DISPOSAL...............................................................................................................................117
 

6. POTENTIAL FOR HUMAN EXPOSURE .........................................................................................119
 

6.1 OVERVIEW.............................................................................................................................119
 

6.2 RELEASES TO THE ENVIRONMENT .................................................................................122
 

6.2.1 Air .......................................................................................................................................122
 

6.2.2 Water...................................................................................................................................124
 

6.2.3 Soil ......................................................................................................................................124
 

6.3 ENVIRONMENTAL FATE.....................................................................................................125
 

6.3.1 Transport and Partitioning...................................................................................................125
 

6.3.2 Transformation and Degradation ........................................................................................126
 

6.3.2.1 Air...............................................................................................................................126
 

6.3.2.2 Water ..........................................................................................................................127
 

6.3.2.3 Sediment and Soil.......................................................................................................128
 

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT ................................130
 

6.4.1 Air .......................................................................................................................................130
 

6.4.2 Water...................................................................................................................................131
 

6.4.3 Sediment and Soil ...............................................................................................................133
 

6.4.4 Other Environmental Media................................................................................................133
 

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE ......................................134
 

6.6 EXPOSURES OF CHILDREN................................................................................................135
 

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES ............................................135
 

6.8 ADEQUACY OF THE DATABASE.......................................................................................136
 

6.8.1 Identification of Data Needs ...............................................................................................136
 

6.8.2 Ongoing Studies..................................................................................................................140
 

7. ANALYTICAL METHODS................................................................................................................141
 

7.1 BIOLOGICAL MATERIALS..................................................................................................141
 

7.2 ENVIRONMENTAL SAMPLES.............................................................................................144
 

7.3 ADEQUACY OF THE DATABASE.......................................................................................152
 

7.3.1 Identification of Data Needs ...............................................................................................153
 

7.3.2 Ongoing Studies..................................................................................................................155
 

8. REGULATIONS AND ADVISORIES ...............................................................................................157
 

9. REFERENCES ....................................................................................................................................161
 

10. GLOSSARY ...................................................................................................................................... 189
 
 

 

 

 

1,1,2,2-TETRACHLOROETHANE 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
 
 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE xvii 

LIST OF FIGURES
 

3-1. Levels of Significant Exposure to 1,1,2,2-Tetrachloroethane - Inhalation......................................... 29
 

3-2. Levels of Significant Exposure to 1,1,2,2-Tetrachloroethane - Oral.................................................. 53
 

3-3. Suggested Metabolic Pathways of 1,1,2,2-Tetrachloroethane............................................................73
 

3-4. Conceptual Representation of a Physiologically Based Pharmacokinetic (PBPK) Model for a
 

Hypothetical Chemical Substance......................................................................................................80
 

3-5. Existing Information on Health Effects of 1,1,2,2-Tetrachloroethane ...............................................95
 

6-1. Frequency of NPL Sites with 1,1,2,2-Tetrachloroethane Contamination.........................................120
 

6-2. Anaerobic Degradation Pathways for 1,1,2,2-Tetrachloroethane.....................................................129
 
1,1,2,2-TETRACHLOROETHANE xviii 

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1,1,2,2-TETRACHLOROETHANE xix 

LIST OF TABLES
 

3-1. Levels of Significant Exposure to 1,1,2,2-Tetrachloroethane - Inhalation........................................ 24
 

3-2. Levels of Significant Exposure to 1,1,2,2-Tetrachloroethane - Oral.................................................. 40
 

3-3. Genotoxicity of 1,1,2,2-Tetrachloroethane In Vitro ...........................................................................66
 

3-4. Genotoxicity of 1,1,2,2-Tetrachloroethane In Vivo ............................................................................67
 

4-1. Chemical Identity of 1,1,2,2-Tetrachloroethane...............................................................................110
 

4-2. Physical and Chemical Properties of 1,1,2,2-Tetrachloroethane......................................................111
 

5-1. Facilities that Produce, Process, or Use 1,1,2,2-Tetrachloroethane..................................................114
 

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

1,1,2,2-Tetrachloroethane..................................................................................................................123
 

7-1. Analytical Methods for Determining 1,1,2,2-Tetrachloroethane in Biological Materials................142
 

7-2. Analytical Methods for Determining 1,1,2,2-Tetrachloroethane in Environmental Materials.........145
 

8-1. Regulations and Guidelines Applicable to 1,1,2,2-Tetrachloroethane .............................................159
 
1,1,2,2-TETRACHLOROETHANE xx 

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1,1,2,2-TETRACHLOROETHANE 1 

1. PUBLIC HEALTH STATEMENT 

This public health statement tells you about 1,1,2,2-tetrachloroethane and the effects of exposure to it. 

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. 1,1,2,2-Tetrachloroethane has been found in at least 329 of the 1,699 current 

or former NPL sites. Although the total number of NPL sites evaluated for this substance is not known, 

the possibility exists that the number of sites at which 1,1,2,2-tetrachloroethane is 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 this substance may be harmful. 

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 1,1,2,2-tetrachloroethane, 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 it. 

You must also consider any other chemicals you are exposed to and your age, sex, diet, family traits, 

lifestyle, and state of health. 
1,1,2,2-TETRACHLOROETHANE 2 

1. PUBLIC HEALTH STATEMENT 

1.1 WHAT IS 1,1,2,2-TETRACHLOROETHANE? 

Description 1,1,2,2-Tetrachloroethane is a synthetic, colorless, dense liquid that does not 

burn easily. 

It has a penetrating, sweet odor similar to chloroform. 

Uses 

 • Manufacturing 

1,1,2,2-Tetrachloroethane production has decreased significantly in the 

United States. In the past, it was used in large amounts to produce other 

chemicals and as an industrial solvent. 

1,1,2,2-Tetrachloroethane was also used to separate fats and oils from other 

substances, to clean and degrease metals, and in paints and pesticides. 

Less toxic chemicals are now available to replace this solvent, and largescale commercial production has stopped, although some production still 

occurs. 

It is presently used as a chemical intermediate, and information about this 

use is limited. 

For more information on the physical and chemical properties of 1,1,2,2-tetrachloroethane and its 

production, disposal and use, see Chapters 4 and 5. 

1.2 WHAT HAPPENS TO 1,1,2,2-TETRACHLOROETHANE WHEN IT ENTERS THE 

ENVIRONMENT? 

Sources Most 1,1,2,2-tetrachloroethane released into the environment eventually 

moves into the air or groundwater. Most of the 1,1,2,2-tetrachloroethane 

released to soil or land will evaporate back to the air. 

If released on the land, 1,1,2,2-tetrachloroethane does not tend to attach to 

soil particles. When released to surface water, much of the chemical will 

evaporate back to the air, while the remainder may break down due to 

reactions with water. Similar reactions can take place in soils and sediments.

How 

1,1,2,2-tetrachloroethane 

breaks down 

Most 1,1,2,2-tetrachloroethane is expected to disappear from groundwater 

and air in about 1 year. 

1,1,2,2-Tetrachloroethane breaks down by losing chlorine atoms. The 

resulting chemicals may also pose a health hazard. 

It has been estimated that 1,1,2,2-tetrachloroethane should not build up 

significantly in the bodies of fish or other aquatic organisms. 

For more information on 1,1,2,2-tetrachloroethane in the environment, see Chapter 6. 
1,1,2,2-TETRACHLOROETHANE 3 

1. PUBLIC HEALTH STATEMENT 

1.3 HOW MIGHT I BE EXPOSED TO 1,1,2,2-TETRACHLOROETHANE? 

General 

population 

Exposure of the general population to 1,1,2,2-tetrachloroethane is expected 

to be very low based on the low concentrations reported for this substance in 

the environment. 

Individuals located near hazardous waste sites and facilities where this 

substance is used may be exposed to 1,1,2,2-tetrachloroethane in 

contaminated air, water, or soil. 

Workplace When a chemical such as 1,1,2,2-tetrachloroethane is used in making other 

chemicals, it is generally contained in closed automatic systems, which are 

not open to the air. Therefore, workers are not usually exposed to high 

levels of 1,1,2,2-tetrachloroethane. 

For more information on human exposure to 1,1,2,2-tetrachloroethane, see Chapter 6. 

1.4 HOW CAN 1,1,2,2-TETRACHLOROETHANE ENTER AND LEAVE MY BODY? 

Enter your body 

 • Inhalation 

 • Ingestion 

 • Dermal contact 

1,1,2,2-Tetrachloroethane can enter your body through the lungs. 

Most of the 1,1,2,2-tetrachloroethane in food or water will rapidly enter the 

body through the digestive tract. 

1,1,2,2-Tetrachloroethane can also enter your body through the skin. 

Leave your body Once in your body, 1,1,2,2-tetrachloroethane is transformed into other 

chemicals called metabolites. Most of these other chemicals leave the body 

in the breath or urine within few days. 

For more information on how 1,1,2,2-tetrachloroethane enters and leaves the body, see Chapter 3. 
1,1,2,2-TETRACHLOROETHANE 4 

1. PUBLIC HEALTH STATEMENT 

1.5 HOW CAN 1,1,2,2-TETRACHLOROETHANE AFFECT MY HEALTH? 

This section looks at studies concerning potential health effects in animal and human studies.

General 

population 

 • Inhalation 

 • Oral 

Breathing concentrated fumes of 1,1,2,2-tetrachloroethane (enough so that 

you notice its sickeningly sweet smell) can rapidly cause drowsiness, 

dizziness, nausea, and vomiting. Most people recover from these effects 

once they are in fresh air. 

Breathing high levels of 1,1,2,2-tetrachloroethane for a long time can cause 

liver damage. 

Drinking very large amounts of 1,1,2,2-tetrachloroethane can cause shallow 

breathing, faint pulse, decreased blood pressure, and possibly 

unconsciousness. 

Laboratory 

animals 

 • Oral Oral exposure to very high doses of 1,1,2,2-tetrachloroethane can result in 

fatigue, difficulty breathing, and unconsciousness. 

Lower dose levels can result in liver damage. 

Cancer An increase in liver tumors was observed in mice following oral exposure. 

The EPA determined that 1,1,2,2-tetrachloroethane is a possible human 

carcinogen. The International Agency for Research on Cancer (IARC) 

determined that 1,1,2,2-tetrachloroethane is not classifiable as to human 

carcinogenicity. 

Further information on the health effects of 1,1,2,2-tetrachloroethane in humans and animals can be found 

in Chapters 2 and 3. 
1,1,2,2-TETRACHLOROETHANE 5 

1. PUBLIC HEALTH STATEMENT 

1.6 HOW CAN 1,1,2,2-TETRACHLOROETHANE AFFECT CHILDREN? 

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

conception to maturity at 18 years of age. 

Effects in children There are no studies evaluating the effect of 1,1,2,2-tetrachloroethane 

exposure on children or immature animals. It is likely that children would 

have the same health effects as adults. We do not know whether children 

would be more sensitive than adults to the effects of 

1,1,2,2-tetrachloroethane. 

It is possible that children are less strongly affected than adults because the 

ability of their body to convert 1,1,2,2-tetrachloroethane into more harmful 

products is immature. 

Birth defects Some effects have been observed in laboratory animals born to females 

exposed to 1,1,2,2-tetrachloroethane during pregnancy. This occurred at 

exposure levels that were also toxic to the mothers. 

Breast milk There is no information on levels of 1,1,2,2-tetrachloroethane in human 

breast milk. 

1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO 1,1,2,2-TETRACHLOROETHANE? 

Consumer 

products 

Families are not likely to be exposed to amounts of 1,1,2,2-tetrachloroethane that are high enough to be a health concern because the chemical is 

no longer used in household products. 

It is possible that some old household products (such as cleaners, 

degreasers, and paints) contain small amounts of 1,1,2,2-tetrachloroethane; 

these products should be kept out of reach from children and used 

according to manufacturer’s instructions. 
1,1,2,2-TETRACHLOROETHANE 6 

1. PUBLIC HEALTH STATEMENT 

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

1,1,2,2-TETRACHLOROETHANE? 

Detecting 

exposure 

1,1,2,2-Tetrachloroethane breakdown products (metabolites) can be 

measured in blood and urine; however, these metabolites are common to 

several types of compounds. 

Measuring 

exposure 

The detection of 1,1,2,2-tetrachloroethane and/or its metabolites in your 

urine cannot be used to predict the kind of health effects that might develop 

from that exposure. 

Information about tests for detecting 1,1,2,2-tetrachloroethane in the body is given in Chapters 3 and 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 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-toexceed 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. 
1,1,2,2-TETRACHLOROETHANE 7 

1. PUBLIC HEALTH STATEMENT 

Some regulations and recommendations for 1,1,2,2-tetrachloroethane include the following: 

Drinking water The EPA has determined that exposure to 1,1,2,2-tetrachloroethane in 

drinking water at a concentration of 0.04 mg/L for up to 10 days is not 

expected to cause any adverse effects in a child. 

The EPA has determined that lifetime exposure to 0.0003 mg/L 

1,1,2,2-tetrachloroethane in drinking water is not expected to cause any 

adverse effects. 

Workplace air OSHA set a legal limit of 5 ppm 1,1,2,2-tetrachloroethane in air averaged 

over an 8-hour work day. 

For more information on regulations and advisories, see Chapter 8. 

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 1-800-CDC-INFO (1-800-232-4636), by e-mail at cdcinfo@cdc.gov, or by writing 

to: 

 Agency for Toxic Substances and Disease Registry 

 Division of Toxicology and Environmental Medicine 

 1600 Clifton Road NE 

 Mailstop F-32 

 Atlanta, GA 30333 

 Fax: 1-770-488-4178 
1,1,2,2-TETRACHLOROETHANE 8 

1. PUBLIC HEALTH STATEMENT 

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/ 
 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 9 

2. RELEVANCE TO PUBLIC HEALTH
 

2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO 1,1,2,2-TETRACHLOROETHANE IN THE UNITED STATES 

1,1,2,2-Tetrachloroethane is currently used as a chemical intermediate in the production of chlorinated 

hydrocarbons. In the past, this substance was used as an industrial solvent and extractant and was even a 

component of a few pesticide formulations; however, its manufacture and use as an end-product appears 

to have ceased in the United States. Present sources of 1,1,2,2-tetrachloroethane are largely attributable 

to fugitive emissions or discharges when it is generated as a byproduct and to emissions or discharges 

stemming from its production and use as a chemical intermediate. 

1,1,2,2-Tetrachloroethane released onto soil is expected to partly volatilize, with the remainder leaching 

into the subsurface soil profile and, possibly, groundwater. Most of the 1,1,2,2-tetrachloroethane released 

to surface water is expected to volatilize, with the remainder dissolving in water where it would undergo 

degradation through hydrolysis and biodegradation. Degradation products include 1,1,2,2-trichloroethylene, 1,2-dichloroethylene, 1,1,2-trichloroethane, 1,2-dichloroethane, and vinyl chloride. In the 

ambient air, the dominant process for removal of 1,1,2,2-tetrachloroethane is the reaction with 

photochemically generated hydroxyl radicals. The half-life of this reaction is 54 days. Some 

1,1,2,2-tetrachloroethane may diffuse upward into the stratosphere where it can participate in reactions 

that produce ozone-destroying chlorine radicals. However 1,1,2,2-tetrachloroethane is not expected to 

contribute significantly to the destruction of the ozone layer since <1% of the tropospheric 1,1,2,2-tetrachloroethane is predicted to reach the stratosphere. 

Reported average concentrations of 1,1,2,2-tetrachloroethane measured in ambient air from both urban 

and rural locations across the United States are generally <10 ppt. However, average urban air 

concentrations as high as 57 ppb have been reported during the 1980’s. More recent data are not 

available, but would be expected to be lower. As reported in the EPA STORET database for 1999–2006 

(www.epa.gov/storet/dw_home.html), 1,1,2,2-tetrachloroethane was detected in approximately 43% of 

12,476 water samples (surface water and groundwater), but only 3% of the samples contained 

1,1,2,2-tetrachloroethane above the quantifiable limit. The range of quantifiable concentrations in these 

water samples was 0.1–25 ppb, with a mean of 0.6 ppb. 1,1,2,2-Tetrachloroethane was detected in 
 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 10 

2. RELEVANCE TO PUBLIC HEALTH 

<0.001% of 166,599 public water system samples collected in the United States between 1993 and 1997. 

1,1,2,2-Tetrachloroethane has not been detected in table-ready foods. 

Based on the low levels of 1,1,2,2-tetrachloroethane measured in the environment and the decreased use 

of this substance in non-industrial settings, exposure of the general population to 1,1,2,2-tetrachloroethane 

is expected to be very low. However, individuals located near hazardous waste sites or facilities where 

1,1,2,2-tetrachloroethane is used as a chemical intermediate may be exposed to this substance by 

inhalation of contaminated air, by ingestion of contaminated drinking water, or by dermal contact with 

contaminated soil. Contaminated air is the most likely source of potential exposure of the general 

population due to the relatively high volatility of 1,1,2,2-tetrachloroethane released to soil and surface 

water. Detection of 1,1,2,2-tetrachloroethane in the vicinity of an abandoned organic chemical 

manufacturing facility provides evidence for significant exposure from contaminated drinking water. 

Children are likely to be exposed to 1,1,2,2-tetrachloroethane by the same routes that affect adults. 

Occupational exposures are expected to occur primarily via inhalation and dermal contact. 

1,1,2,2-Tetrachloroethane is well absorbed from the respiratory and gastrointestinal tracts in humans and 

laboratory animals, and absorption through the skin after dermal exposure has been demonstrated in 

animals. Following oral or inhalation exposure, 1,1,2,2-tetrachloroethane is extensively metabolized and 

excreted mainly as metabolites in the urine and breath. In rats and mice, 1,1,2,2-tetrachloroethane is 

metabolized to trichloroethanol, trichloroacetic acid, and dichloroacetic acid, which is then broken down 

to glyoxalic acid, oxalic acid, and carbon dioxide; a small percentage of the dose is exhaled in the breath 

as the parent compound. Both reductive and oxidative metabolism occurs, producing reactive radical and 

acid chloride intermediates, respectively. 

2.2 SUMMARY OF HEALTH EFFECTS 

A limited amount of information is available on the health effects of 1,1,2,2-tetrachloroethane in humans. 

The information in humans is generally very dated and incomplete and provides no information on doseresponse. There has been only one epidemiological study involving this chemical and this study did not 

report on or classify exposure levels. However, the human database does suggest that 1,1,2,2-tetrachloroethane can target certain systems (nervous system, liver, mucous membranes) following high-dose 

exposure; it is also possible that more modern studies would be able to detect other types of effects in 

exposed populations. Reports of inhaled and ingested 1,1,2,2-tetrachloroethane indicate that central 

nervous system depression is the predominant effect of high-level acute exposure. Irritation of the 
 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 11 

2. RELEVANCE TO PUBLIC HEALTH 

mucous membranes also has been observed following acute exposure to high concentrations of 

1,1,2,2-tetrachloroethane vapor. Occupational studies suggest that repeated inhalation exposures can 

affect the liver as well as the nervous system; hepatic effects that have been reported include liver 

enlargement and jaundice. 

Animal studies have clearly demonstrated that the central nervous system and liver are the main targets of 

1,1,2,2-tetrachloroethane toxicity following acute- and intermediate-duration inhalation and oral 

exposure. Neurotoxicity has mainly been associated with near-lethal to lethal exposures; typical effects 

include a progression of clinical signs ranging from lethargy and incoordination to respiratory depression 

and loss of consciousness. Hepatic effects are prevalent at lower levels of exposure and include increases 

in serum enzymes and liver fat content, increased hepatic deoxyribonucleic acid (DNA) synthesis and 

mitotic activity, hepatocellular cytoplasmic vacuolation and other mild histological alterations, fatty 

degeneration, and hepatocellular necrosis. Chronic oral exposure to 1,1,2,2-tetrachloroethane induced 

liver cancer (hepatocellular carcinoma) in mice. 

Little information is available on other effects of 1,1,2,2-tetrachloroethane. Reduced body weight gain 

and weight loss are effects of repeated oral exposures in rats and mice that generally occurred at high dose 

levels and, in dietary studies, were partly due to decreased food consumption from taste aversion. 

Intermediate-duration inhalation and oral exposures have been reported to cause hematological and 

immunological alterations in rats and rabbits. Chronic oral exposure to high doses induced kidney lesions 

(chronic inflammation and acute toxic nephrosis) in mice. Reproductive and developmental toxicity have 

not been adequately evaluated. Intermediate-duration oral exposure to doses that caused body weight loss 

also caused atrophy in reproductive tissues in male and female rats; alterations in sperm motility and 

estrus cycle of unclear toxicological significance were observed at lower doses. There were no effects on 

reproductive function in male rats following intermediate-duration inhalation of a low concentration of 

1,1,2,2-tetrachloroethane, but testing of reproductive performance in female animals has not been 

conducted. Gestational exposure to 1,1,2,2-tetrachoroethane caused fetotoxicity in rats (decreased fetal 

body weight) and mice (litter resorptions) at oral doses that were maternally toxic, but fetuses were not 

examined for malformations. 

A greater detailed discussion of 1,1,2,2-tetrachloroethane-induced neurological effects, hepatic effects 

and cancer follows. The reader is referred to Section 3.2, Discussion of Health Effects by Route of 

Exposure, for additional information on these effects and other health effects. 
 

 

 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 12 

2. RELEVANCE TO PUBLIC HEALTH 

Neurological Effects. Acute inhalation exposure to high levels of 1,1,2,2-tetrachloroethane caused 

clinical signs of neurotoxicity in humans that included drowsiness, nausea, headache, and weakness, and 

at extremely high concentrations, unconsciousness and respiratory failure. A limited experimental study 

found similar effects (vertigo and fatigue) in two volunteers who were exposed to 146 ppm for 30 minutes 

or 336 ppm for 10 minutes, which are levels that also caused irritation of the mucous membranes. 

In animals that inhaled 1,1,2,2-tetrachloroethane, clinical signs of neurotoxicity (e.g., incoordination, loss 

of reflexes, labored respiration, prostration, and loss of consciousness) typically preceded death, which 

occurred at concentrations as low as 1,000–1,168 ppm for 1.5–4 hours in rats and mice. A sublethal 

exposure of 576 ppm for 30 minutes caused reduced activity and alertness in rats and guinea pigs. The 

effective concentration for a 50% decrease in spontaneous motor activity in rats was 360 ppm for a 6-hour 

exposure. Intermediate-duration intermittent exposure to high concentrations of 1,1,2,2-tetrachloroethane 

caused neurological effects in mice similar to those observed in acute studies. Data on the neurotoxicity 

of single or repeated daily exposures to low levels of 1,1,2,2-tetrachloroethane vapor were not located. 

Information on the neurotoxicity of oral exposure to 1,1,2,2-tetrachloroethane in humans is available from 

case reports. People who intentionally ingested a lethal amount usually lost consciousness within 

approximately 1 hour and died 3–20 hours postingestion. No deaths occurred in patients who were 

accidentally given an estimated oral dose of 68–118 mg/kg as medicinal treatment for hookworm, 

although they experienced loss of consciousness and other clinical signs of narcosis that included shallow 

breathing, faint pulse, and pronounced lowering of blood pressure. In animals, lethargy and central 

nervous system depression occurred in rats gavaged with 270–300 mg/kg/day for 1–12 days or 

208 mg/kg/day for 21 days. Information on neurological effects of lower acute oral doses are limited to a 

poorly reported rat study in which a single gavage dose of 100 mg/kg caused ataxia and 50 mg/kg caused 

decreased passive avoidance to an electric shock, possibly due to an increased threshold of shock 

perception due to a subtle anesthetic effect. In studies of dietary (nonbolus) exposure, no clinical signs of 

neurotoxicity occurred in rats and mice that were exposed to 320 and 1,400 mg/kg/day, respectively, for 

14 weeks. Comprehensive neurobehavioral evaluations (functional observational batteries, FOBs) in 

these studies showed no effects at doses as high as 80 mg/kg/day in the rats and 700 mg/kg/day in the 

mice (higher doses not evaluated). 

Hepatic Effects and Cancer. Some humans exposed to 1,1,2,2-tetrachloroethane vapors in the 

workplace have developed jaundice and an enlarged liver. Specific clinical signs were not associated 

with specific exposure levels, although vapor concentrations in one study ranged from 1.5 to 248 ppm. 
 

 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 13 

2. RELEVANCE TO PUBLIC HEALTH 

Liver cirrhosis was not increased in an epidemiological study of men occupationally exposed to 

unmeasured levels of 1,1,2,2-tetrachloroethane fumes in a clothing plant. Liver congestion and necrosis 

were observed in the autopsies of three humans who died following inhalation or oral exposure to 

1,1,2,2-tetrachloroethane. 

Information on the hepatotoxicity of inhaled 1,1,2,2-tetrachloroethane includes gross observations of fatty 

degeneration in rats, mice, and guinea pigs that died following acute- or intermediate-duration 

intermittent exposures to ≥1,000 ppm concentrations. Studies in which rats were exposed to lower 

concentrations of 1,1,2,2-tetrachloroethane for 4 hours, 4 hours/day for 8 of 10 days, or 5 days/week for 

15 weeks found generally mild hepatic effects as indicated by clinical chemistry and histological 

alterations, but reporting limitations, insufficient quantitative data, and other study inadequacies preclude 

identification of reliable effects levels. Effects in these studies included increases in serum enzymes, 

increases in serum and liver triglycerides, changes in serum protein fractions, and fine droplet fatty 

degeneration and cytoplasmic vacuolation. 

Hepatic effects of oral exposure included hepatocellular degeneration in mice exposed to a lethal dietary 

dose of 2,394 mg/kg/day for 6 days, increased serum aspartate aminotransferase (AST) in rats given a 

single gavage dose of 574 mg/kg, and increased liver cell DNA synthesis, mitotic activity, and 

centrilobular swelling in rats and/or mice exposed to 75–300 mg/kg/day by gavage for 4 days. Liver 

effects in intermediate-duration studies included cytoplasmic vacuolation in rats exposed to 

104 mg/kg/day by gavage for 21 days, and hepatocellular degeneration in mice exposed to 

337.5 mg/kg/day by gavage for 16 days or 599 mg/kg/day in the diet for 15 days. Comprehensive 

14-week dietary studies showed that the liver was the most sensitive target of 1,1,2,2-tetrachloroethane 

toxicity for intermediate-duration exposure in rats and mice. Hepatic effects in the rats included 

biologically significant increases in serum alanine aminotransferase (ALT), sorbitol dehydrogenase 

(SDH), alkaline phosphatase (ALP) and bile acids, hepatocyte necrosis, bile duct hyperplasia, and liver 

pigmentation at 170–320 mg/kg/day. Hepatic effects in the mice included biologically significant 

increases in serum ALT and SDH, and necrosis, pigmentation, and bile duct hyperplasia at 

≥300 mg/kg/day. 

In the only chronic study of 1,1,2,2-tetrachloroethane, rats were exposed to time-weighted average 

(TWA) doses of 0, 62, or 108 mg/kg/day (males) or 0, 43, or 76 mg/kg/day (females) by gavage on 

5 days/week for 78 weeks, followed by an observation period of 32 weeks. Fatty degeneration of the liver 

occurred at 108 mg/kg/day, but no significant increases in tumor incidences were observed. Mice of both 
 

 

 

 

1,1,2,2-TETRACHLOROETHANE 14 

2. RELEVANCE TO PUBLIC HEALTH 

sexes were similarly exposed to TWA doses of 0, 142, or 284 mg/kg/day for 78 weeks followed by 

12 weeks of observation. Significant, dose-related increases in the incidence of hepatocellular carcinoma 

were observed in males (3/36, 13/50, and 44/49 in the control, low-dose, and high-dose groups, 

respectively) and females (1/40, 30/48, and 43/47, respectively). Based mainly on the results of this 

study, in an assessment conducted in 1994, the EPA has classified the carcinogenicity of 1,1,2,2-tetrachloroethane as Group C, possible human carcinogen. The International Agency for Research on Cancer 

(IARC) cancer classification for 1,1,2,2-tetrachloroethane is Group 3, not classifiable with regard to its 

carcinogenicity to humans. The National Toxicology Program (NTP) has not classified 1,1,2,2-tetrachloroethane for human carcinogenicity. 

The mode of action of the hepatocarcinogenicity of 1,1,2,2-tetrachloroethane is incompletely 

characterized. It is likely that liver tumor formation by 1,1,2,2-tetrachloroethane involves its metabolism 

to one or more active compounds, although there is no direct evidence linking one or more metabolites to 

its carcinogenic effects. Genotoxicity studies provide only limited evidence of a genotoxic mode of 

action. 1,1,2,2-Tetrachloroethane has weak genotoxic activity, with in vitro genotoxicity tests generally 

reporting negative results except for assays of sister chromatid exchange (SCE) and cell transformation; 

in vivo tests of genotoxicity have shown a similar pattern. 

2.3 MINIMAL RISK LEVELS (MRLs) 

Estimates of exposure levels posing minimal risk to humans (MRLs) have been made for 1,1,2,2-tetrachloroethane. An MRL is defined as an estimate of daily human exposure to a substance that is likely to 

be without an appreciable risk of adverse effects (noncarcinogenic) over a specified duration of exposure. 

MRLs are derived when reliable and sufficient data exist to identify the target organ(s) of effect or the 

most sensitive health effect(s) for a specific duration within a given route of exposure. MRLs are based 

on noncancerous health effects only and do not consider carcinogenic effects. MRLs can be derived for 

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

methodology does not exist to develop MRLs for dermal exposure. 

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 
 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 15 

2. RELEVANCE TO PUBLIC HEALTH 

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 acute-duration inhalation MRL has been derived for 1,1,2,2-tetrachloroethane due to insufficient data. 

Reports in humans indicate that high-dose acute inhalation exposure to 1,1,2,2-tetrachloroethane can 

cause central nervous system depression and mucous membrane irritation (Coyer 1944; Hamilton 1917; 

Lehmann and Schmidt-Kehl 1936), but exposure-response data are lacking or insufficient. The 

preponderance of information on the acute inhalation toxicity of 1,1,2,2-tetrachloroethane in animals 

pertains to neurological and hepatic effects of near-lethal to lethal exposures to concentrations above 

approximately 1,000 ppm (Carpenter et al. 1949; Horiuchi et al. 1962; NIOSH 1978; Pantelitsch 1933; 

Schmidt et al. 1980b). The lowest effective concentration for a serious neurotoxic effect (50% decrease 

in spontaneous motor activity) was 360 ppm for 6 hours in rats (Horvath and Frantik 1973). No 

information is available on neurotoxicity at lower concentrations, precluding identification of a lessserious lowest-observed-adverse-effect level (LOAEL) or no-observed-adverse-effect level (NOAEL). 

Hepatic effects that include histological alterations and serum and liver biochemical changes have been 

reported in studies of rats exposed to concentrations as low as 60 ppm for 4 hours (Schmidt et al. 1980b) 

and 2.2 ppm for 4 hours/day for 8 of 10 days (Gohlke and Schmidt 1972; Schmidt et al. 1972), but these 

studies are inadequate for identifying a reliable NOAEL or LOAEL and deriving an acute inhalation 

MRL due to insufficient data on incidence, magnitude, and/or severity of effects. 

No intermediate-duration inhalation MRL has been derived for 1,1,2,2-tetrachloroethane due to 

insufficient data. Intermittent intermediate-duration exposure to lethal concentrations of 1,1,2,2-tetrachloroethane (7,000–9,000 ppm) caused central nervous system depression and fatty liver degeneration in 

rats and mice (Horiuchi et al. 1962). Information on effects of lower concentrations of 1,1,2,2-tetrachloroethane is available from poorly reported studies in rats and rabbits (Kulinskaya and Verlinskaya 

1972; Schmidt et al. 1972; Shmuter 1977; Truffert et al. 1977; Union Carbide Corporation 1947). 

Findings in these studies included transient histological alterations in the liver of rats exposed to 560 ppm 

for 5 hours/day, 5 days/week for 15 weeks (Truffert et al. 1977), hematological alterations and increased 

liver fat content in rats exposed to 1.9 ppm for 4 hours/day for 265 days (Schmidt et al. 1972), alterations 

in serum acetylcholinesterase activity in rabbits exposed to 1.5 ppm for 3 hours/day, 6 days/week for 7– 

8.5 months (Kulinskaya and Verlinskaya 1972), and immunological alterations in rabbits exposed to 0.3– 

14.6 ppm for 3 hours/day, 6 days/week for 8–10 months (Shmuter 1977). None of these studies are 
 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 16 

2. RELEVANCE TO PUBLIC HEALTH 

adequate for identification of reliable NOAELs or LOAELs or MRL derivation due to insufficient data on 

incidence, magnitude, and/or severity of effects and other reporting limitations. 

No chronic-duration inhalation MRL has been derived for 1,1,2,2-tetrachloroethane due to insufficient 

data. Information on the chronic inhalation toxicity of 1,1,2,2-tetrachloroethane in humans is available 

from several occupational studies (Jeney et al. 1957; Lobo-Mendonca 1963; Minot and Smith 1921; 

Norman et al. 1981) that are inadequate for identification of effect levels due to limitations that include 

insufficient characterization of exposure levels, lack of control data, dermal exposures, and/or mixed 

chemical exposures. Although not sufficient for identification of effect levels or MRL derivation, the 

occupational studies provide limited supporting information on the neurotoxicity and hepatotoxicity of 

1,1,2,2-tetrachloroethane. Chronic inhalation studies in animals have not been performed. 

Oral MRLs 

No acute-duration oral MRL has been derived for 1,1,2,2-tetrachloroethane due to insufficient data. 

Single oral doses in the range of 68–118 mg/kg are estimated to be serious LOAELs for neurotoxicity in 

humans based on unconsciousness and other clinical signs observed in case reports (Hepple 1927; 

Lilliman 1949; Mant 1953; Sherman 1953; Ward 1955). The preponderance of information on the acute 

oral toxicity of 1,1,2,2-tetrachloroethane in animals is provided by gavage studies in rats and mice 

exposed to near-lethal to lethal dose levels. Rats were more sensitive than mice and the nervous system 

was more sensitive than the liver. Central nervous system depression and death, but no clearly adverse 

effects in the liver, occurred in rats exposed to gavage doses as low as 270–300 mg/kg/day for 1–4 days 

or 208 mg/kg/day for 13–14 days (Hanley et al. 1988; NTP 1993a, 1993b, 1996). Information on effects 

of lower acute oral doses in animals is limited to a rat study in which a single gavage dose of 100 mg/kg 

caused ataxia and 50 mg/kg caused decreased passive avoidance to an electric shock, possibly due to an 

increased threshold of shock perception due to a subtle anesthetic effect (Wolff 1978). The possible 

anesthetic effect suggests that 50 mg/kg is a LOAEL for neurotoxicity in rats, but evaluation of the study 

and the significance of the effect level is complicated by incomplete reporting and insufficient 

quantitative data. Derivation of an acute MRL is precluded by the uncertain reliability of the 

50 mg/kg/day LOAEL in rats and, particularly, its proximity to the 68–118 mg/kg doses causing serious 

neurotoxicity in humans. 
 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 17 

2. RELEVANCE TO PUBLIC HEALTH 

•	 An MRL of 0.5 mg/kg/day has been derived for intermediate-duration (15–364 days) oral 

exposure to 1,1,2,2-tetrachloroethane. 

Liver effects data from a comprehensive 14-week study in rats were used as the basis for an intermediateduration oral MRL. In this study (NTP 2004a), groups of 10 male and 10 female F344 rats were exposed 

to diet containing 1,1,2,2-tetrachloroethane in reported average daily doses of 0, 20, 40, 80, 170, or 

320 mg/kg/day for 14 weeks. The study was comprehensive in scope and included extensive evaluations 

of histology, clinical chemistry, and neurotoxicity (FOBs). Effects included increases in hepatic 

cytoplasmic vacuolization at 20 mg/kg/day, liver weight at 40 mg/kg/day, and hepatocellular hypertrophy 

at 80 mg/kg/day. These hepatic effects are not considered adverse because the severity of the vacuolation 

was minimal to mild and did not increase with dose, and the increases in liver weight and hepatocellular 

hypertrophy are considered adaptive responses to chemical exposure. Increases in serum ALT and SDH 

and decreases in serum cholesterol also occurred at ≥80 mg/kg/day, but the magnitudes of these changes 

were biologically significant only at ≥170 mg/kg/day. Other effects that occurred at 170 and 

320 mg/kg/day included increases in serum ALP and bile acids, hepatocyte necrosis, bile duct 

hyperplasia, hepatocellular mitotic alterations, foci of cellular alterations, and liver pigmentation. As 

discussed by NTP (2004a), increases in serum ALT and SDH are specific markers of hepatocellular 

necrosis or increased cell membrane permeability (leakage) in rodents; increases in bile acids are markers 

of cholestasis, impaired hepatocellular function, or hepatocellular injury; increased ALP is another marker 

of cholestasis; and decreased serum cholesterol is possibly indicative of liver dysfunction (impaired 

cholesterol biosynthesis). There was no evidence of neurotoxicity, as shown by negative FOB testing at 

doses as high as 80 mg/kg/day (higher doses not tested) and lack of clinical signs in all dose groups. 

Additional information regarding the design and results of this study is presented in Appendix A. This 

study identified a NOAEL of 80 mg/kg/day and a LOAEL of 170 mg/kg/day for systemic toxicity based 

on adverse liver-related serum chemistry changes and histological manifestations of hepatocellular 

damage. This LOAEL is lower than or equal to the LOAELs for reproductive effects in males 

(320 mg/kg/day) and females (170 mg/kg/day). A LOAEL for neurotoxicity was not identified because 

there were no clinical signs of neurotoxicity or exposure-related findings in the FOB at doses as high as 

80 mg/kg/day (highest tested dose in the FOB). 

NTP (2004a) also tested mice in a similarly designed 14-week dietary study that supports the rat data in 

showing that the liver was the most sensitive target of 1,1,2,2-tetrachloroethane toxicity. Hepatic effects 

in the mice included minimal hepatocellular hypertrophy, increases in serum SDH, ALT, and bile acids, 

and decreased serum cholesterol at 160–200 mg/kg/day, and increases in serum ALP and 5’-nucleotidase, 

necrosis, pigmentation, and bile duct hyperplasia at 300–370 mg/kg/day. The magnitudes of the serum 
 

 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 18 

2. RELEVANCE TO PUBLIC HEALTH 

chemistry changes were biologically significant at ≥300 mg/kg/day in females and ≥370 mg/kg/day in 

males. Based on the adverse serum chemistry and histopathological changes at 300 mg/kg/day and higher 

doses, this study identifies a LOAEL of 300 mg/kg/day for liver toxicity in mice; the corresponding 

NOAEL is 200 mg/kg/day. Additional information on the intermediate-duration oral toxicity of 

1,1,2,2-tetrachloroethane is available from a 21-day gavage study in rats (NTP 1996), a 16-day gavage 

study in mice (NTP 1993d), 6-week gavage studies in rats and mice (NCI 1978), and 15-day diet studies 

in rats and mice (NTP 2004a). These studies are mainly dose range-finding studies that used small 

numbers of animals and had limited or no evaluations of clinical chemistry and histology. The lowest 

LOAELs in these studies were 100–104 mg/kg/day for reduced body weight gain and hepatocyte 

cytoplasmic vacuolation in rats exposed by gavage (NCI 1978; NTP 1996) and 337.5 mg/kg/day for 

hepatocellular degeneration in mice exposed by gavage (NTP 1993d). The NTP (2004a) 14-week dietary 

study is the best basis for MRL derivation because it tested wider ranges of doses and varieties of end 

points, identified lower LOAELs, and used a more relevant method of oral exposure than the other 

intermediate-duration studies. 

The NTP (2004a) study found that the rat was more sensitive than the mouse, as reflected by the liver 

toxicity findings identifying a LOAEL and NOAEL that were lower in the rats (80 and 40 mg/kg/day) 

than in the mice (170 and 80 mg/kg/day). Potential points of departure for the intermediate-duration 

MRL were derived by benchmark dose (BMD analysis) of NTP (2004a) rat liver data. Data for liver 

weight, hepatocyte necrosis, and serum ALT, SDH, bile acids, and cholesterol in one or both sexes were 

selected for modeling because these end points showed statistically significant changes and best reflected 

the progression and spectrum of hepatotoxic effects. All available dichotomous models in the EPA 

Benchmark Dose Software (BMDS version 1.3.2) were fit to the incidence data for hepatocyte necrosis. 

The continuous-variable models in the software were applied to the data for changes in relative liver 

weight and serum ALT, SDH, bile acids, and cholesterol. 

Appropriate model fits were obtained for the hepatocyte necrosis and serum bile acids data in both sexes 

and serum ALT and SDH data in males. A summary of the predicted BMDs and 95% lower confidence 

limits (BMDLs) using the best fitting models for these end points, as well as details of the BMD 

modeling, are presented in Appendix A. For the hepatocyte necrosis incidence data, predicted doses 

associated with 30, 20, 10, 5, and 1% extra risks were calculated as possible alternative benchmark 

responses (BMRs) for the best fitting model. Conventionally, a 10% extra risk has served as a point of 

departure for MRL determination. However, because the NTP (2004a) study examined only 10 animals 

per group, the limit of detection is above the 10% level, likely in the 20–30% range. For the continuous 
 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 19 

2. RELEVANCE TO PUBLIC HEALTH 

data, the calculated BMDs and BMDLs are estimates of the doses associated with a change of 1 standard 

deviation from the control. Predicted doses associated with an increase of 100% (i.e., 2-fold) were also 

calculated for the best fitting model for the changes in liver enzymes (serum ALT and SDH), as an 

increase of this magnitude is sometimes considered to be an indicator of clinical significance for these 

effects. 

The lowest BMDLs were calculated for the male rat serum ALT and SDH data using 1 standard deviation 

below the control mean as the BMR. The BMDLs for serum ALT (26.56 mg/kg/day) and serum SDH 

(25.13 mg/kg/day) are approximately half of the BMDL of 53.88 mg/kg/day calculated using the female 

rat hepatocyte necrosis incidence data and a BMR of 10%. The BMDLs for the serum enzyme changes 

appear to be overly conservative predictions that have questionable biological plausibilty because they are 

substantially below the study NOAEL of 80 mg/kg/day. Effects occurring at the NOAEL included 

increases in serum ALT and SDH that were not adverse and hepatocyte necrosis in 1/10 females. The 

BMDL10 of 53.88 mg/kg/day for minimal hepatocyte necrosis in female rats was selected as the point of 

departure for the MRL because it is reasonably consistent with the observed findings. The intermediateduration oral MRL of 0.5 mg/kg/day was derived by dividing the BMDL by a composite uncertainty 

factor of 100 (10 for extrapolation from humans and 10 for human variability). 

No chronic-duration oral MRL has been derived for 1,1,2,2-tetrachloroethane due to insufficient data. 

Information on the chronic oral toxicity of 1,1,2,2-tetrachloroethane is limited to a 78-week 

carcinogenicity bioassay in rats and mice that were exposed by gavage (NCI 1978). Interpretation of the 

rat study is confounded by high incidences of endemic chronic murine pneumonia, although this is 

unlikely to have contributed to effects observed in the liver; based on an increased incidence of hepatic 

fatty changes, a NOAEL of 62 mg/kg/day and LOAEL of 108 mg/kg/day were identified in the rats. The 

mouse study identified a serious LOAEL of 284 mg/kg/day for reduced survival and lethal kidney lesions 

(acute toxic tubular nephrosis), but high incidences of hepatocellular tumors in all exposed groups 

(142 and 284 mg/kg/day) precluded evaluation of noncancer effects in the liver and identification of a 

NOAEL or less-serious LOAEL in the mice. No chronic oral MRL was derived because lower LOAELs 

were identified in the more comprehensive and sensitive 14-week dietary study (NTP 2004a) used to 

derive the intermediate-duration MRL. 
1,1,2,2-TETRACHLOROETHANE 20 

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1,1,2,2-TETRACHLOROETHANE 21 

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 1,1,2,2-tetrachloroethane. 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. 

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 

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 
 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 22 

3. HEALTH EFFECTS 

"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 1,1,2,2-tetrachloroethane are indicated in Table 3-2 and Figure 3-2. Because cancer effects could occur at lower 

exposure levels, Figure 3-2 also shows a range for the upper bound of estimated excess risks, ranging 

from a risk of 1 in 10,000 to 1 in 10,000,000 (10-4 to 10-7), as developed by EPA. 

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. 

As discussed below, the database on health effects of 1,1,2,2-tetrachloroethane is limited by a paucity of 

studies in humans. The information in humans is generally very dated, incomplete, and unsuitable for 

determination of reliable effect levels. 

3.2.1 Inhalation Exposure 

3.2.1.1 Death 

A few human deaths have been reported following excessive inhalation exposure to 1,1,2,2-tetrachloroethane. Immediately after World War I, gastrointestinal and neurological distress were reported 

following occupational exposure to a varnish containing 1,1,2,2-tetrachloroethane that was used to cover 

fabric airplane wings. Although workers generally recovered, at least 4 of 14 workers later became 

confused, delirious, comatose, and finally died (Willcox et al. 1915). Autopsies revealed extreme liver 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 23 

3. HEALTH EFFECTS 

destruction and fatty degeneration of the liver. The levels of 1,1,2,2-tetrachloroethane in the air were not 

measured, so inhaled concentrations that may cause death in humans are not known. 

Inhalation of 1,1,2,2-tetrachloroethane has also been shown to cause death in animals. Mortality resulted 

from exposure to concentrations of 1,000–1,253 ppm for 4–6 hours in rats (Carpenter et al. 1949; Deguchi 

1972; Schmidt et al. 1980b; Smyth et al. 1969), 1,168–5,900 ppm for 1.5–3 hours in mice (Horiuchi et al. 

1962; Pantelitsch 1933), and 5,050–6,310 ppm for 30 minutes in rats and guinea pigs (NIOSH 1978). 

Mortality was reported in rats and mice repeatedly exposed to 1,1,2,2-tetrachloroethane vapors (Horiuchi 

et al. 1962). For example, exposure of six male rats at a concentration of 9,000 ppm (2 hours/day, 

once/week for a total of five exposures) resulted in 100% mortality; three of the six rats died following 

the first exposure period. All nine male mice exposed to 1,1,2,2-tetrachloroethane vapors at a 

concentration of 7,000 ppm for 2 hours once a week died during a 29-day study. All exposures from 

reliable studies that caused death in rats, mice, and guinea pigs are recorded in Table 3-1 and plotted in 

Figure 3-1. 

3.2.1.2 Systemic Effects 

No studies were located regarding musculoskeletal or dermal effects in humans or animals following 

inhalation exposure to 1,1,2,2-tetrachloroethane. The systemic effects observed in humans and animals 

after inhalation exposure to 1,1,2,2-tetrachloroethane are discussed below. The highest NOAEL and all 

LOAEL values from each reliable study for systemic end points in each species and duration category are 

recorded in Table 3-1 and plotted in Figure 3-1. 

Respiratory Effects. Minor effects on the respiratory system are caused by 1,1,2,2-tetrachloroethane 

in humans. At a concentration of 13 ppm, but not 2.9 ppm, mucosal irritation occurred in two humans 

exposed for 10–30 minutes. Odor was noticed at the lowest concentration tested (2.9 ppm) (Lehmann and 

Schmidt-Kehl 1936). 

Labored respiration was observed in rats and guinea pigs exposed to 1,1,2,2-tetrachloroethane vapors at 

lethal concentrations (5,050 or 6,310 ppm) for 30 minutes; histological examinations showed no 

treatment-related lesions in the lungs (NIOSH 1978). There was no histopathological evidence of 

exposure-related effects on the respiratory system of a monkey exposed to a time-weighted average 

(TWA) concentration of 1,974 ppm for 2 hours/day, 6 days/week for 9 months (Horiuchi et al. 1962), 

although the monkey study is limited by only one test animal and no control. 
60

1000

61

5050

118

1253

72

5900

188

1168

65

6310

Table 3-1 Levels of Significant Exposure to 1,1,2,2-Tetrachloroethane - Inhalation 

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) 

ACUTE EXPOSURE Death 

1 Rat 

(Sherman) 

4 hr 

System 

NOAEL 

(ppm) 

Less Serious 

(ppm) 

LOAEL 

Serious 

(ppm) 

1000 (2/6 died) 

Reference Chemical Form 

Carpenter et al. 1949 

2 Rat 

(SpragueDawley) 

30 min 5050 (3/10 died) NIOSH 1978 

3 Rat 

(Wistar) 

4 hr 1253 M (LC50) Schmidt et al. 1980b 

4 Mouse 

(NS) 

3 hr 5900 M (3/10 died) Horiuchi et al. 1962 

5 Mouse 

(NS) 

1.5-2 hr 1168 (3/3 died) Pantelitsch 1933 

6 Gn Pig 

(Hartley) 

30 min 6310 (3/10 died) NIOSH 1978 
69

576 50506310631063106310576 50506310

73

5900

91

600

92

800

Table 3-1 Levels of Significant Exposure to 1,1,2,2-Tetrachloroethane - Inhalation (continued) 

a 

Key to Species 

Figure (Strain) 

Systemic 

7 Rat 

(SpragueDawley) 

8 Mouse 

(NS) 

9 Mouse 

(Cb) 

10 Mouse 

(Cb) 

Exposure/ 

Duration/ 

Frequency 

(Route) 

30 min 3 hr 3 hr 3 hr 

System 

Resp 

Cardio Hepatic Renal Endocr Ocular Bd Wt Hepatic Hepatic Hepatic 

LOAEL 

NOAEL 

(ppm) 

Less Serious 

(ppm) 

Serious 

(ppm) 

Reference Chemical Form 

576 5050 (labored respiration) NIOSH 1978 

6310 6310 6310 6310 

576 

6310 

5050 (lacrimation) 5900 M (congestion and fatty 

degeneration of the liver) 

Horiuchi et al. 1962 

600 F (increased triglycerides 

and total lipids and decreased ATP in liver) 

Tomokuni 1969 

800 F (increased triglycerides 

and decreased phospholipids in liver) 

Tomokuni 1970 
68

576 50506310631063106310

576

6310

93

360

62

576

5050

798

1022

66

576 5050

Table 3-1 Levels of Significant Exposure to 1,1,2,2-Tetrachloroethane - Inhalation (continued) 

a 

Key to Species 

Figure (Strain) 

11 Gn Pig 

(Hartley) 

Neurological 

12 Rat 

(NS) 

13 Rat 

(SpragueDawley) 

14 Mouse 

(NS) 

15 Gn Pig 

(Hartley) 

Exposure/ 

Duration/ 

Frequency 

(Route) System NOAEL (ppm) Less Serious (ppm) 

LOAEL 

Serious 

(ppm) 

Reference Chemical Form 

30 min Resp 576 5050 (labored respiration) NIOSH 1978 

Cardio Hepatic Renal Endocr Ocular 

6310 6310 6310 6310 

576 (lacrimation, squinting, 

eye closure) 

Bd Wt 6310 

6 hr 360 (50% decreased motor 

activity) 

Horvath and Frantik 197

30 min 576 (reduced activity and 

alertness) 

5050 (narcosis) NIOSH 1978 

1.5-2 hr 1022 (prostration, loss of 

reflexes) 

Pantelitsch 1933 

30 min 576 (reduced activity) 5050 (narcosis and tremors) NIOSH 1978 
801

9000

799

7000

80

1974

76

90009000

9000

800

7000

802

1974

Table 3-1 Levels of Significant Exposure to 1,1,2,2-Tetrachloroethane - Inhalation (continued) 

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) 

INTERMEDIATE EXPOSURE Death 

16 Rat 

(NS) 

29 d 2-3 d/wk 2 hr/d 

System 

NOAEL 

(ppm) 

Less Serious 

(ppm) 

LOAEL 

Serious 

(ppm) 

9000 M (6/6 died) 

Reference Chemical Form 

Horiuchi et al. 1962 

17 Mouse 

(NS) 

29 d 1 d/wk 2 h/d 

7000 M (9/9 died) Horiuchi et al. 1962 

Systemic 

18 Monkey 

(Macaca cynomolga) 

9 mo 6 d/wk 2 hr/d 

Hepatic 1974 M (fatty degeneration) Horiuchi et al. 1962 

19 Rat 

(NS) 

29 d 2-3 d/wk 2 hr/d 

Hemato 9000 M (decreases red cell count 

and hemoglobin content) 

Horiuchi et al. 1962 

Hepatic 9000 M (congestion and fatty 

degeneration) 

Bd Wt 9000 M 

20 Mouse 

(NS) 

29 d 1 d/wk 2 h/d 

Hepatic 7000 M (congestion and fatty 

degeneration) 

Horiuchi et al. 1962 

Neurological 

21 Monkey 

(Macaca cynomolga) 

9 mo 6 d/wk 2 hr/d 

1974 M (near unconsciousness) Horiuchi et al. 1962 
807

9000

809

1.9

Table 3-1 Levels of Significant Exposure to 1,1,2,2-Tetrachloroethane - Inhalation (continued) 

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System NOAEL (ppm) Less Serious (ppm) 

LOAEL 

Serious 

(ppm) 

Reference Chemical Form 

22 Rat 

(NS) 

29 d 2-3 d/wk 2 hr/d 

9000 M (ataxia and loss of 

consciousness) 

Horiuchi et al. 1962 

Reproductive 

23 Rat 

(NS) 

9 mo 4 hr/d 1.9 M Schmidt et al. 1972 

a The number corresponds to entries in Figure 3-1. ATP = adenosine tri-phosphate; Bd Wt = body weight; Cardio = cardiovascular; d = day(s); Endocr = endocrine; F = Female; Gastro = gastrointestinal; Gn pig = gui

hematological; hr = hour(s); Immuno = immunological; LC50 = lethal concentration, 50% kill, LOAEL = lowest-observed-adverse-effect level; M = male; min = minutmonth(s); NOAEL = no-observed-adverse-effect level; NS = not specified; occup = occupational; Resp = respiratory; wk = week(s) 
Death 

Respiratory Cardiovascular Hepatic Renal Endocrine Ocular Body Weight Neurological 

Figure 3-1 Levels of Significant Exposure to 1,1,2,2-Tetrachloroethane - Inhalation
	

Acute (≤14 days)
	

Systemic 

ppm 

10000 

6g 11g 7r 11g 7r 11g 7r 11g 7r 11g 7r 4m 8m 

2r 11g 7r 7r 15g 13r 

3r 5m 

1000 1r 14m

10m 

11g 7r 9m 11g 7r 15g 13r 

12r 

100 

1,1,2,2-TETRACHLOROETHANE

3. HEALTH EFFECTS

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 

29
Death 

Hematological Hepatic Body Weight Neurological Reproductive 

Figure 3-1 Levels of Significant Exposure to 1,1,2,2-Tetrachloroethane - Inhalation (Continued)

Intermediate (15-364 days) 

Systemic 

ppm 

10000 16r 19r 19r 19r 22r 

17m 20m 

18k 21k 

1000 

100 

10 

23r 

1 

1,1,2,2-TETRACHLOROETHANE

3. HEALTH EFFECTS

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 

30
 

 

 

 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 31 

3. HEALTH EFFECTS 

Cardiovascular Effects. Humans exposed to 1,1,2,2-tetrachloroethane in factories showed few, if 

any, effects on the cardiovascular system. World War II army workers who were exposed to unknown 

levels of 1,1,2,2-tetrachloroethane during its use as a solvent in a clothing impregnation process showed 

no increase in deaths due to cardiovascular diseases in a 30-year follow-up period (Norman et al. 1981). 

When compared with cause-, age-, race-, and calendar year-specific U.S. mortality rates, the standard 

mortality ratio (SMR) for cardiovascular disease was 0.79 (confidence intervals not reported); additional 

information on this study is presented in Section 3.2.1.7. Workers exposed to 1,1,2,2-tetrachloroethane in 

a chemical plant in Italy showed no important clinical changes in cardiovascular function (Gobbato and 

Bobbio 1968). Exposure levels were not measured in either of these studies. 

No pathological changes in rat hearts were found after a 6-hour exposure to 100 ppm (Deguchi 1972). 

Myocardial damage was found in 1 of 10 rats following exposure to 6,310 ppm for 30 minutes; no such 

effect occurred in a guinea pig subjected to this same exposure (NIOSH 1978). 

No histopathological changes were seen in the heart of a monkey that was exposed to a TWA 

concentration of 1,974 ppm 1,1,2,2-tetrachloroethane for 2 hours/day, 6 days/week for 9 months 

(Horiuchi et al. 1962). However, only one monkey was studied, and a control was not included. 

Gastrointestinal Effects. Humans exposed to 1,1,2,2-tetrachloroethane in the workplace often 

developed gastric distress including pain, nausea, vomiting, loss of appetite, and loss of body weight. 

Such symptoms were found in workers in the fabric airplane wing varnish industry in World War I 

(Coyer 1944; Willcox et al. 1915), in a penicillin factory in Czechoslovakia (Jeney et al. 1957), and in a 

jewelry factory in India (Lobo-Mendonca 1963). Although specific complaints were not associated with 

specific levels of exposure, the exposure levels in the facilities ranged from 1 to 248 ppm. The adverse 

health effects generally disappeared when the workers left their employment. 

Two volunteers who inhaled 1,1,2,2-tetrachloroethane fumes for 10–30 minutes experienced nausea and 

vomiting after exposure to 2.9 ppm for 20 minutes (Lehmann and Schmidt-Kehl 1936). 

Data regarding gastrointestinal effects in animals following inhalation exposure to 1,1,2,2-tetrachloroethane are limited. One monkey exposed to 1,974 ppm for 2 hours/day, 6 days/week for 9 months had 

diarrhea and anorexia between the twelfth and fifteenth exposures and subsequently recovered (Horiuchi 

et al. 1962). However, no control monkey was included. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 32 

3. HEALTH EFFECTS 

Hematological Effects. An increase in the number of large mononuclear cells, white blood cells, 

and platelets, and slight anemia, were found in workers in an artificial silk factory who were exposed to 

1,1,2,2-tetrachloroethane vapors (Minot and Smith 1921). 1,1,2,2-Tetrachloroethane levels were not 

accurately measured. 

Two of three male rats that were intermittently exposed to 9,000 ppm for 29 days showed decreases in red 

blood cells and hemoglobin content (Horiuchi et al. 1962). A monkey exposed to 1,974 ppm 

intermittently for 9 months showed sporadic changes in hematocrit, red blood cell, and white blood cell 

counts, but these changes showed no clear trend and only one animal was tested (Horiuchi et al. 1962). 

Hepatic Effects. One of the most significant systemic effects of 1,1,2,2-tetrachloroethane is on the 

liver. Some humans exposed to 1,1,2,2-tetrachloroethane vapors in the workplace have developed 

jaundice and an enlarged liver (Coyer 1944; Horiuchi et al. 1962; Jeney et al. 1957; Koelsch 1915; 

Willcox et al. 1915). Specific clinical signs were not associated with specific exposure levels. Vapor 

concentrations were reported in one study to range from 1.5 to 248 ppm (Jeney et al. 1957). 

Liver degeneration, as evidenced by liver congestion and necrosis, was observed in the autopsies of two 

humans who died after exposure to 1,1,2,2-tetrachloroethane (Willcox et al. 1915). World War II army 

workers who were exposed to unknown levels of 1,1,2,2-tetrachloroethane during its use as a solvent in a 

clothing impregnation process showed no increase in deaths due to cirrhosis of the liver in a 30-year 

follow-up period (Norman et al. 1981). When compared with cause-, age-, race-, and calendar yearspecific U.S. mortality rates, the SMR for liver cirrhosis was 0.48 (confidence intervals not reported). 

Additional information on this study is presented in Section 3.2.1.7. 

The liver is also the major target organ for 1,1,2,2-tetrachloroethane toxicity in animals. Fine droplet 

fatty degeneration of the liver was observed in rats following a single exposure to 60 ppm for 4 hours or 

exposure to 2 ppm for 4 hours/day for 8 of 10 days, but there were no clear changes in serum or liver 

chemistry indices at these exposure levels (Gohlke and Schmidt 1972; Schmidt et al. 1972). This 

histological alteration appeared to be mild and was accompanied by clear or suggestive increases in 

hepatic ascorbic acid and serum glutamate dehydrogenase and decreases in serum triglycerides at 

102 ppm, increases in serum triglycerides and hexobarbital sleep time at 307 ppm, and increases in serum 

alanine aminotransferase and leukin aminopeptidase at 613 ppm (Schmidt et al. 1972), suggesting that 

102 ppm was a minimal LOAEL for acute hepatic effects. No treatment-related histological effects were 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 33 

3. HEALTH EFFECTS 

found in the liver of rats or guinea pigs exposed to 6,310 ppm of 1,1,2,2-tetrachloroethane for 30 minutes 

(NIOSH 1978), although rats that were exposed to 9,000 ppm for 2 hours/day, 2 days/week for 4 weeks 

showed fatty livers (Horiuchi et al. 1962). Hepatic lipids and triglycerides were increased in mice 

exposed to 600–800 ppm for 3 hours (Tomokuni 1969, 1970), and fatty degeneration of the liver occurred 

in mice exposed to a lethal concentration of 5,900 ppm for 3 hours (Horiuchi et al. 1962). Rabbits that 

were exposed to 15 ppm for 7–11 months showed early signs of liver degeneration at necropsy 

(Navrotskiy et al. 1971). A single monkey exposed to a TWA concentration of 1,974 ppm of 

1,1,2,2-tetrachloroethane for 2 hours/day, 6 days/week for 9 months also showed fatty degeneration of the 

liver (Horiuchi et al. 1962). 

Additional information on liver effects following intermediate-duration exposure to 1,1,2,2-tetrachloroethane is available from poorly reported studies that cannot be used to identify reliable effect levels. For 

example, Truffert et al. (1977) reported unquantified increases in relative liver weights and 

histopathological liver alterations in female rats exposed to 1,1,2,2-tetrachloroethane vapors at a reported 

concentration of 560 mL/m3

, for 5 or 6 hours/day, 5 days/week for up to 15 weeks. The histological liver 

alterations were observed after nine exposures and included granular appearance, cytoplasmic 

vacuolization, and evidence of hyperplasia (increase in number of binuclear cells and appearance of 

mitosis), but the alterations regressed after 19 exposures and were no longer observed after 39 exposures. 

Incidences and severity of the liver lesions were not reported. Reliable effect levels cannot be established 

for this study due to the lack of information regarding incidence and severity of effects and exposureresponse (due to the use of a single exposure level), as well as uncertainty regarding the actual exposure 

concentration. If it is assumed that mL/m3 is a volume/volume vapor concentration, then the reported 

concentration is equivalent to 560 ppm. If it is assumed that 560 mL is the volume of liquid volatilized in 

1 m3 of air, then the reported concentration is equivalent to 130,325 ppm, a level over 100 times higher 

than the acute LC50. 

Renal Effects. No recent studies were located regarding renal effects in humans following inhalation 

exposure to 1,1,2,2-tetrachloroethane. Fatty degeneration and congestion of the kidney were found in one 

female who had died following inhalation of 1,1,2,2-tetrachloroethane over a 2–3-month period (Willcox 

et al. 1915), but exposure concentrations were not defined. 

No treatment-related histological effects were found in the kidneys of rats or guinea pigs exposed to 

6,310 ppm for 30 minutes (NIOSH 1978), rats exposed to 613 ppm for 4 hours (Schmidt et al. 1972), or 

rats exposed to 2 ppm for 4 hours/day for 8 of 10 days (Gohlke and Schmidt 1972). Similarly, no 
 

 

 

 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 34 

3. HEALTH EFFECTS 

treatment-related histopathological lesions in the kidney were found in one monkey exposed to a TWA 

concentration of 1,974 ppm for 2 hours/day, 6 days/week for 9 months (Horiuchi et al. 1962), although 

this study is limited by the use of a single animal. 

Endocrine Effects. No studies were located regarding endocrine effects in humans following 

inhalation exposure to 1,1,2,2-tetrachloroethane. 

No treatment-related histological effects were found in the adrenals of rats or guinea pigs exposed to 

6,310 ppm for 30 minutes (NIOSH 1978) or pancreas of one monkey exposed to a TWA concentration of 

1,974 ppm for 2 hours/day, 6 days/week for 9 months (Horiuchi et al. 1962). There were no changes in 

thyroid histology, morphometry (diameter and number of follicles and epithelial nuclei, height of 

follicular epithelium), or absorption of injected 131I in rats exposed to 2 ppm for 4 hours/day for 8 of 

10 days (Gohlke and Schmidt 1972). 

Ocular Effects. Humans exposed to 1,1,2,2-tetrachloroethane vapors (130 ppm) for 10 minutes 

experienced ocular mucosal irritation (Lehmann and Schmidt-Kehl 1936). Similarly, guinea pigs exposed 

to 576 ppm for 5 minutes exhibited eye closure and squinting; by 15 minutes, lacrimation was common 

(NIOSH 1978). Rats showed these effects at 5,050 ppm. These ocular effects are due to direct contact of 

the eyes with the vapors, rather than a true systemic effect due to inhalation of the vapor. 

Body Weight Effects. Humans exposed to 1,1,2,2-tetrachloroethane vapors in an occupational 

setting experienced a 5–15-pound weight loss (Parmenter 1921). However, this weight loss was probably 

attributable to gastrointestinal disturbances (i.e., nausea, diarrhea, and vomiting) (Parmenter 1921). 

No effects on body weight were found in several inhalation studies in animals (Horiuchi et al. 1962; 

NIOSH 1978; Schmidt et al. 1972, 1980b). 

3.2.1.3 Immunological and Lymphoreticular Effects 

No studies were located regarding immunological or lymphoreticular effects in humans following 

inhalation exposure to 1,1,2,2-tetrachloroethane. 

Rabbits were exposed 0, 0.3, 1.5, or 14.6 ppm of 1,1,2,2-tetrachloroethane for 3 hours/day, 6 days/week 

for 8–10 months (Shmuter 1977). Animals were vaccinated with typhoid vaccine 1.5, 4.5–5, and 7.5– 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 35 

3. HEALTH EFFECTS 

8 months after the initiation of 1,1,2,2-tetrachloroethane exposure. Significant increases and decreases in 

total antibody levels were observed in the 0.3 and 14.6 ppm groups, respectively. No significant changes 

in 7S-typhoid antibody levels were observed. Significant alterations in the levels of “normal hemolysins 

to the Forssmann antigen of sheep erythrocytes” were observed in the 1.5 and 14.6 ppm groups; levels 

were increased at 1.5 ppm after 1.5, 2, and 2.5 months of exposure and decreased after 4 months of 

exposure, and decreased at 14.6 ppm3 during the first 6 months of exposure. Increases in the 

electrophoretic mobility of specific antibodies were also reported. Exposure to 14.6 ppm resulted in a 

decrease in the relative content of antibodies in the  globulin fraction and an increase in the α and 

 fractions. This is a poorly reported study that provides inadequate quantitative data. The reporting 

limitations, end points of uncertain toxicological significance, and inconsistent patterns of response 

preclude assessing biological significance and identification of a NOAEL or LOAEL. No 

histopathological changes were noted in the spleens of rats that inhaled 100 ppm 1,1,2,2-tetrachloroethane 

for 6 hours (Deguchi 1972). The significance of this finding is unclear due to a lack of immune function 

tests. 

3.2.1.4 Neurological Effects 

Volunteers who inhaled 1,1,2,2-tetrachloroethane (116 ppm and higher for 10–30 minutes) reported being 

dizzy. These effects did not occur when the exposure was 13 ppm (Lehmann and Schmidt-Kehl 1936). 

Humans exposed to 1,1,2,2-tetrachloroethane fumes in the workplace showed symptoms such as 

headache, tremors, dizziness, numbness, and drowsiness (Hamilton 1917; Jeney et al. 1957; LoboMendonca 1963; Minot and Smith 1921; Parmenter 1921). Length of exposure was not specifically 

noted, but the reports seem to indicate that the exposures were generally for a period of about 18 months 

or less. Exposure levels were only noted in one study, and these ranged from 9 to 98 ppm, with 

significant skin exposure in addition to the inhalation exposure (Lobo-Mendonca 1963). 

In acute-duration experiments, rats showed a 50% decrease in spontaneous motor activity after being 

exposed to 360 ppm for 6 hours (Horvath and Frantik 1973). As the concentration of, or duration of 

exposure to, 1,1,2,2-tetrachloroethane increased, mice, rats, and guinea pigs showed some combination of 

a loss of reflexes, loss of spontaneous motor activity, ataxia, prostration, and narcosis (Lazarew 1929; 

Pantelitsch 1933; NIOSH 1978). Rats and guinea pigs that were exposed for 30 minutes had reduced 

activity at 576 ppm and narcosis at 5,050 ppm (NIOSH 1978), and mice showed prostration and loss of 

reflexes after being exposed to 1,022–1,091 ppm for 2 hours (Lazarew 1929; Pantelitsch 1933). Narcosis 

was observed in a cat exposed to 8,300 ppm for 5 hours (Lehmann 1911). Rats exposed to 9,000 ppm for 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 36 

3. HEALTH EFFECTS 

2 hours/day, twice a day for 4 weeks exhibited hyperactivity, ataxia, and then unconsciousness (Horiuchi 

et al. 1962). One monkey exposed to a TWA of 1,974 ppm of 1,1,2,2-tetrachloroethane for 2 hours/day, 

6 days/week for 9 months exhibited unconsciousness after each 2-hour exposure, starting at the 15th 

exposure (Horiuchi et al. 1962). 

The highest NOAEL and all LOAEL values from each reliable study for neurological end points in each 

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

3.2.1.5 Reproductive Effects 

No studies were located regarding reproductive effects in humans following inhalation exposure to 

1,1,2,2-tetrachloroethane. 

Male rats were exposed to 0 or 2.2 ppm of 1,1,2,2-tetrachloroethane 4 hours/day for up to 8 days in a 

10-day period (Gohlke and Schmidt 1972; Schmidt et al. 1972). Reproductive function was not tested, 

but evaluations included histological examinations of the testes in groups of seven control and seven 

treated males following the second, fourth, and eighth exposures. This study is limited by imprecise and 

incomplete reporting of results. It was noted that testicular histopathology, described as atrophy of the 

seminal tubules with strongly restricted or absent spermatogenesis, was observed in five exposed animals 

following the fourth exposure; data for the other time periods and the control group were not reported. 

The biological significance of the testicular histological changes is unclear because these changes 

apparently were not observed at the end of the study, and there were no effects on reproductive function 

in male rats that were chronically exposed to a similar concentration of 1,1,2,2-tetrachloroethane 

(1.9 ppm) (Schmidt et al. 1972). 

Male rats were exposed to 0 or 1.9 ppm of 1,1,2,2-tetrachloroethane 4 hours/day for 265 days. One week 

before the end of the exposure period, each of 7 control and 7 exposed males was mated with 5 unexposed 

virgin females, yielding corresponding groups of 35 mated females. The offspring were observed for 

84 days and were examined macroscopically for malformations. Other reported study end points were 

percentage of mated females having offspring, littering interval, time to 50% littered, total number of 

pups, pups per litter, average birth weight, postnatal survival on days 1, 2, 7, 14, 21, and 84, and sex ratio 

and average body weight on postnatal day 84. No macroscopic malformations or significant group 

differences in the other indices were found, indicating that 1.9 ppm was a NOAEL for male reproductive 

toxicity in rats. 
 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 37 

3. HEALTH EFFECTS 

Rats and guinea pigs that were exposed to 6,310 ppm (43,350 mg/m3

) 1,1,2,2-tetrachloroethane for 

30 minutes had no exposure-related organ weight or gross or histological changes in the testes, 

epididymides, ovaries, or uterus when examined 14 days post-exposure (NIOSH 1978). There were no 

histopathological changes in the testes of one monkey that was exposed to a TWA concentration of 

1,974 ppm for 2 hours/day, 6 days/week for 9 months (Horiuchi et al. 1962). Lack of histopathology, 

however, does not necessarily indicate that these male and female animals could produce appropriate 

numbers of healthy offspring. Since no mating studies with rats, guinea pigs, or monkeys exposed to high 

levels of 1,1,2,2-tetrachloroethane vapors have been conducted, no reproductive effect levels are indicated 

in Table 3-1 or Figure 3-1. 

3.2.1.6 Developmental Effects 

No studies were located regarding developmental effects in humans following inhalation exposure to 

1,1,2,2-tetrachloroethane. 

The potential for 1,1,2,2-tetrachloroethane-induced developmental effects in animals was assessed in a 

study that included inhalation exposure of male rats to 1.9 ppm 1,1,2,2-tetrachloroethane 4 hours/day, for 

an unspecified number of times during a 9-month period (Schmidt et al. 1972). One week before the end 

of the exposure period, exposed males and control males were mated with unexposed females and the 

F1 generation was observed for 12 weeks. There was no effect on the number of offspring per litter, 

neonatal body weight, viability of the offspring, sex ratios, and body weight on day 84. No gross 

malformations were observed in the offspring. 

3.2.1.7 Cancer 

Mortality experience was evaluated in 1,099 white male World War II army workers who were exposed 

to 1,1,2,2-tetrachloroethane in 10 plants during its use as a solvent for impregnating clothing with 

N-dichloro-hexachloro-diphenyl-urea as a protectant against mustard gas (Norman et al. 1981). Exposure 

could have included the dermal route and was not measured, estimated, or documented on a man-for-man 

basis, but wasbased on job category (processing, laundry, or dry cleaning duties). Information from seven 

of the companies indicated that exposure to the solvent ranged from 5 weeks to 1 year (average 

approximately 5 months), and the workers were followed for 31 years. When compared with cause-, 
 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 38 

3. HEALTH EFFECTS 

age-, race-, and calendar year-specific U.S. mortality rates, the SMR for all malignancies was 

0.96 (confidence intervals not reported). When the exposed group was compared with 1,319 workers in 

29 other plants that used a water suspension instead of 1,1,2,2-tetrachloroethane in the impregnating 

process, there were slight increases for mortality from leukemia and aleukemia (relative risk [RR]=2.72, 

90% confidence interval [CI] 0.96–7.70) and cancer of the genital organs (RR=1.58, 90% CI 0.58–4.83). 

This comparison showed no increases for the following cancer sites: all malignancies, buccal cavity and 

pharynx, digestive organs and peritoneum, respiratory system, urinary organs, and other lymphatic. Since 

the numbers of deaths were small (four from leukemia and aleukemia and three from gential organ 

cancers in the solvent-exposed group), the increases in risk were small, no significant excesses were 

found, and other confounding factors may have been present (i.e., exposure to other chemicals and a lack 

of occupational histories following exposure), the authors concluded that the results are difficult to 

interpret and the observed increases in cancer mortality may not have been due to 1,1,2,2-tetrachloroethane exposure. This information is inconclusive as to whether 1,1,2,2-tetrachloroethane causes cancer 

in humans. 

No other studies were located regarding carcinogenicity in animals following inhalation exposure to 

1,1,2,2-tetrachloroethane. 

3.2.2 Oral Exposure 

3.2.2.1 Death 

A number of human suicides from drinking 1,1,2,2-tetrachloroethane have been reported. In reports of 

intentional ingestion of lethal amounts of 1,1,2,2-tetrachloroethane (Elliott 1933; Forbes 1943; Hepple 

1927; Lilliman 1949; Mant 1953; Sherman 1953), subjects usually lost consciousness within 

approximately 1 hour and died 3–20 hours postingestion, depending on the amount of food in the 

stomach. Postmortem examinations showed gross congestion in the esophagus, stomach, kidneys, spleen, 

and trachea, gross congestion and edema in the lungs, and histological effects of congestion and cloudy 

swelling in the lungs, liver, and/or kidneys (Hepple 1927; Mant 1953). Amounts of 1,1,2,2-tetrachloroethane recovered from the stomach and intestines of these deceased subjects included 12 mL (Hepple 

1927), 25 g (Lilliman 1949), 48.5 mL (Mant 1953), and 425 mL (Mant 1953). Assuming a density of 

1.594 g/mL and an average body weight of 70 kg, the approximate minimum doses ingested in these 

cases are estimated to be approximately 273, 357, 1,100, and 9,700 mg/kg, respectively, although the 

actual doses are likely higher because the estimates are based on amounts of chemical recovered from the 
 

 

 

 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 39 

3. HEALTH EFFECTS 

gastrointestinal tract. No deaths occurred in eight patients (six males and two females) who were 

accidentally given 3 mL (68 mg/kg, using the above assumptions), or three patients (one young man, one 

young woman, one 12-year-old girl) accidentally administered 2 or 3 mL (98–118 mg/kg, using the 

assumed density and reported body weights), as medicinal treatment for hookworm (Sherman 1953; Ward 

1955). 

Mortality following oral exposure to 1,1,2,2-tetrachloroethane has been assessed in rats and mice. Single 

dose gavage LD50 values in rats range from 250 to 800 mg/kg (Gohlke et al. 1977; NTP 2004a; Schmidt et 

al. 1980a; Smyth et al. 1969). Gavage exposure to 540 mg/kg/day for 3–5 days (NTP 1993a, 1993b), 

300 mg/kg/day for 3 days (Hanley et al. 1988), or 208 mg/kg/day for 13–21 days (NTP 1996) also caused 

mortality in rats. In mice, a gavage dose of 1,350 mg/kg/day for 3 days was lethal (NTP 1993d). Dietary 

exposure caused moribundity or death in rats at 558 mg/kg/day for 11 days (NTP 2004a), pregnant mice 

at 2,120 mg/kg/day for 14 days (NTP 1991b), and mice at 2,394 mg/kg/day for 6 days (NTP 1993c, 

2004). NCI (1978) performed 6-week range-finding gavage studies that appear to have used mortality 

and body weight as the only end points to assess toxicity. The 316 mg/kg treatment level resulted in 

reported mortality in rats, but not mice. There was no treatment-related mortality in rats or mice 

administered 1,1,2,2-tetrachloroethane in the diet for 14 weeks at concentrations resulting in reported 

daily doses as high as 320 and 1,400 mg/kg/day, respectively (NTP 2004a). 

Significantly decreased survival was observed in male and female mice administered 1,1,2,2-tetrachloroethane via oral gavage for 78 weeks at a reported TWA dose of 284 mg/kg/day (NCI 1978). Male and 

female rats were also administered 1,1,2,2-tetrachloroethane at TWA doses of 62 and 108 mg/kg/day 

(males) and 43 and 76 mg/kg/day (females) for 78 weeks (NCI 1978). Reduced survival was reported in 

the high-dose female rats, but survival in the female rats may have been influenced by high incidences of 

chronic murine pneumonia in controls and treatment groups alike; there was no apparent effect on 

survival in the male rats. 

All reliable LOAEL values from each reliable study for death in each species and duration category are 

recorded in Table 3-2 and plotted in Figure 3-2. 

3.2.2.2 Systemic Effects 

No studies were located regarding musculoskeletal effects in humans or animals following oral exposure 

to 1,1,2,2-tetrachloroethane. The highest NOAEL and all LOAEL values from each reliable study for 
23

273

52

357

13

1100

200

9700

781

300

34

250

767

540

771

540

785

208

Table 3-2 Levels of Significant Exposure to 1,1,2,2-Tetrachloroethane - Oral 

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) 

ACUTE EXPOSURE Death 

1 Human once 

(IN) 

System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

273 M (death) 

Reference Chemical Form 

Hepple 1927 

2 Human once 

(IN) 357 (death) Lilliman 1949 

3 Human once 

(IN) 1100 M (death) Mant 1953 

4 Human once 

(IN) 9700 M (death) Mant 1953 

5 Rat 

(OsborneMendel) 

3 d 1 x/d (GO) 

300 M (1/5 died) Dow 1988 

6 Rat 

(NS) 

once (GO) 250 M (LD50) Gohlke et al. 1977 

7 Rat 

(Fischer- 344) 

3 d 1 x/d (GO) 

540 M (5/5 males died) NTP 1993a 

8 Rat 

(Fischer- 344) 

3-5 d 1 x/d (GO) 

540 (5/5 males and 5/5 

females died) 

NTP 1993b 

9 Rat 

(Fischer- 344) 

13-14 d 7 d/wk 1 x/d (GO) 

208 M (5/5 moribund or dead) NTP 1996 
761

558

778

800

26

330

28

319

795

2120

775

1350

763

2394

53

357357

Table 3-2 Levels of Significant Exposure to 1,1,2,2-Tetrachloroethane - 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 

10 Rat 

(Fischer- 344) 

11 d ad lib (F) 

558 F (moribund) NTP 2004a 

11 Rat 

(NS) 

once (G) 800 (LD50) NTP 2004a 

12 Rat 

(Wistar-C) 

once (GO) 330 M (LD50) Schmidt et al. 1980a 

13 Rat 

(CarnworthWistar) 

once (G) 319 M (LD50) Smyth et al. 1969 

14 Mouse 

(CD-1) 

11 d Gd 6-16 ad lib (F) 

2120 F (2/10 maternal deaths) NTP 1991b 

15 Mouse 

(B6C3F1) 

3 d 1 x/d (GO) 

1350 (5/5 males and 5/5 

females moribund or dead) 

NTP 1993d 

16 Mouse 

(B6C3F1) 

6 d ad lib (F) 

Systemic 

17 Human once 

(IN) Gastro 

2394 M (2/5 died) 

357 (congestion of stomach 

lining) 

NTP 2004a Lilliman 1949 

Hepatic 357 (slight liver congestion) 
12

9600

9600

15

11001100

1100

11001100

779

287

574

810

300150

300

Table 3-2 Levels of Significant Exposure to 1,1,2,2-Tetrachloroethane - Oral (continued) 

a 

Key to Species 

Figure (Strain) 

18 Human 19 Human 20 Rat 

(SpragueDawley) 

21 Rat 

(OsborneMendel) 

Exposure/ 

Duration/ 

Frequency 

(Route) 

once (IN) once (IN) once (GO) 3 d 1 x/d (GO) 

LOAEL 

System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

Serious 

(mg/kg/day) 

Reference Chemical Form 

Resp 9600 M (lung collapse) Mant 1953 

Gastro 9600 M (congestion of 

esophagus and stomach) 

Resp 1100 M (extreme lung congestion Mant 1953

and edema) 

Cardio 1100 M (epicardial and 

endocardinal anoxic petechial hemorrhage) 

Gastro 1100 M (pronounced congestion 

of gastric mucosa) 

Hepatic Renal 

1100 M 1100 M 

Hepatic 287 M 574 M (increased serum AST 

and ALT) 

Cottalasso et al. 1998 

Hepatic 300 M Dow 1988 

Bd Wt 150 M 300 M (16% reduced body 

weight) 
816

34

768

135

270

774

135

270

2

300300

815

987

765

2394

54

68

Table 3-2 Levels of Significant Exposure to 1,1,2,2-Tetrachloroethane - 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 

22 Rat 

(SpragueDawley) 

11d GD 6-16 ad lib (F) 

Bd Wt 34 F NTP 1991a 

23 Rat 

(Fischer- 344) 

12 of 14 d 1 x/d (GO) 

Bd Wt 135 M 270 M (55% reduced body 

weight gain) 

NTP 1993a 

24 Rat 

(Fischer- 344) 

12 of 14 d 1 x/d (GO) 

Bd Wt 135 270 (17-22% decreased final 

body weight) 

NTP 1993b 

25 Mouse 

(B6C3F1) 

4 d 1 x/d (GO) 

Hepatic Bd Wt 

300 M 300 M 

Dow 1988 

26 Mouse 

(CD-1) 

11 d Gd 6-16 ad lib (F) 

Bd Wt 987 F (14% decreased 

maternal body weight gain during treatment) 

NTP 1991b 

27 Mouse 

(B6C3F1) 

Neurological 

28 Human 

6 d ad lib (F) once (IN) 

Hepatic 2394 (hepatocellular 

degeneration) 

68 (unconsciousness and 

other signs of narcosis) 

NTP 2004a Sherman 1953 
29

98

783

300

769

135 270

773

135 270

812

591558

55

25

50

100

784

300

766

4788

Table 3-2 Levels of Significant Exposure to 1,1,2,2-Tetrachloroethane - Oral (continued) 

a 

Key to 

Figure 

29 30 31 32 33 34 35 36 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System NOAEL (mg/kg/day) 

LOAEL 

Less Serious 

(mg/kg/day) 

Serious 

(mg/kg/day) 

Reference Chemical Form 

Human once 

(IN) 98 (unconsciousness and Ward 1955 other signs of narcosis) 

Rat (OsborneMendel) 

3-4 d 1 x/d (GO) 

300 M (CNS depression and Dow 1988

debilitation) 

Rat (Fischer- 344) 

12 of 14 d 1 x/d (GO) 

135 M 270 M (lethargy) NTP 1993a

Rat (Fischer- 344) 

1 d (GO) 135 270 (lethargy) NTP 1993b

Rat (Fischer- 344) 

11 d ad lib (F) 

591 M (lethargy) NTP 2004a 

558 F (lethargy) 

Rat (Wistar) 

once (G) 25 F 50 F (increased electric shock Wolff 1978 perception threshold) 100 F (ataxia) 

Mouse (B6C3F1) 

4 d 1 x/d (GO) 

300 M Dow 1988 

Mouse (B6C3F1) 

4 d ad lib (F) 

4788 M (lethargy) NTP 2004a 
814

98

794

987

35

316

36

100

178

56

100

786

104

104104

Table 3-2 Levels of Significant Exposure to 1,1,2,2-Tetrachloroethane - 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 

37 Rat 

(SpragueDawley) 

11d GD 6-16 ad lib (F) 

98 F NTP 1991a 

38 Mouse 

(CD-1) 

11 d Gd 6-16 ad lib (F) 

INTERMEDIATE EXPOSURE Death 

39 Rat 

(OsborneMendel) 

6 wk 5 d/wk (GO) 

Systemic 

40 Bd Wt Rat (OsborneMendel) 6 wk 5 d/wk (GO) 

987 F 

316 F (5/5 died) 

100 M 178 M (38% reduced body 

weight gain) 

NTP 1991b NCI 1978 NCI 1978 

56 F 100 F (24% reduced body 

weight gain) 

41 Hepatic Rat (Fischer- 344) 21 d 7 d/wk 1 x/d 

(GO) 

104 M (increased liver weight, 

cytoplasmic vacuolation) 

NTP 1996 

Renal Bd Wt 

104 M 104 M 
751

32032032032032040

80

32032080

170

762

400

500

300

38

316

Table 3-2 Levels of Significant Exposure to 1,1,2,2-Tetrachloroethane - Oral (continued) 

Exposure/ 

Duration/ 

a 

Key to Species Frequency 

Figure (Strain) (Route) 

42 Rat 14 wk 

ad lib (Fischer- 344) 

(F) 

43 Rat 15 d 

ad lib (Fischer- 344) 

(F) 

44 Mouse 6 wk 

5 d/wk (B6C3F1) 

(GO) 

System 

Resp 

Cardio Gastro Hemato Musc/skel Hepatic Renal Endocr Bd Wt 

Dermal 

Bd Wt Bd Wt 

LOAEL 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

Serious 

(mg/kg/day) 

Reference Chemical Form 

320 NTP 2004a 

320 

320 320 320 

b

40 80 (increased serum ALT 

and SDH, decreased serum cholesterol) 

320 

320 

80 170 (29% reduced final body 

weight) 

400 F 500 F (alopecia and 

acanthosis) 

NTP 2004a 

300 (25-29% reduced final 

body weight) 

316 NCI 1978 
776

337.5

675

755

13601360136080

160

13601360200

370

764

599599

Table 3-2 Levels of Significant Exposure to 1,1,2,2-Tetrachloroethane - 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 

45 Mouse 

(B6C3F1) 

12 of 16 d 1 x/d (GO) 

Hepatic 337.5 F (hepatocellular 

degeneration) 

NTP 1993d 

Bd Wt 675 

46 Mouse 

(B6C3F1) 

14 wk ad lib (F) 

Cardio 1360 NTP 2004a 

Gastro 1360 Musc/skel Hepatic 

1360 

80 F 160 F (increased serum ALT, 

SDH and 5'-nucleotidase; decreased serum cholesterol) 

Renal 1360 Endocr 1360 Bd Wt 200 M 370 M (12% reduced body 

weight gain) 

47 Mouse 

(B6C3F1) 

15 d ad lib (F) 

Hepatic 599 (hepatocellular 

degeneration) 

NTP 2004a 

Bd Wt 599 (10-14% reduced final 

body weight) 
811

104 208

752

80

777

337.5 675

758

1360

813

599

753

17080

320170

Table 3-2 Levels of Significant Exposure to 1,1,2,2-Tetrachloroethane - 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 

48 Rat 

(Fischer- 344) 

21 d 7 d/wk 1 x/d (GO) 

104 M 208 M (lethargy) NTP 1996 

49 Rat 

(Fischer- 344) 

14 wk ad lib (F) 

80 NTP 2004a 

50 Mouse 

(B6C3F1) 

12 of 16 d 1 x/d (GO) 

337.5 675 (lethargy) NTP 1993d 

51 Mouse 

(B6C3F1) 

14 wk ad lib (F) 

1360 NTP 2004a 

52 Mouse 

(B6C3F1) 

15 d ad lib (F) 

599 (hyperactivity) NTP 2004a 

Reproductive 

53 Rat 

(Fischer- 344) 

14 wk ad lib (F) 

170 M 80 F 

320 M (atrophy of prostate 

gland, seminal vesicle and testicular germinal epithelium) 

170 F (uterine atrophy and 

changes in lengths of estrus cycle stages) 

NTP 2004a 
760

1360

45

284

44

10810862 1081081081086243

10876

Table 3-2 Levels of Significant Exposure to 1,1,2,2-Tetrachloroethane - 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 

54 Mouse 

(B6C3F1) 

14 wk ad lib (F) 

CHRONIC EXPOSURE Death 

55 Mouse 

(B6C3F1) 

78 wk 5 d/wk (GO) 

1360 

284 (reduced survival in both 

sexes; 55% in females) 

NTP 2004a NCI 1978 

Systemic 

56 Rat 

(OsborneMendel) 

78 wk 5 d/wk (GO) 

Cardio 108 M NCI 1978 

Gastro 108 M Hepatic 62 M 108 M (fatty metamorphosis) Renal 108 M Endocr 108 M Dermal 108 M Bd Wt 62 M 

43 F 

108 M (18% depressed body 

weight) 

76 F (14% depressed body 

weight) 
603

284284284284142

284

284284284

789

10876

791

284

Table 3-2 Levels of Significant Exposure to 1,1,2,2-Tetrachloroethane - 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 

57 Mouse 

(B6C3F1) 

78 wk 5 d/wk (GO) 

Resp 284 NCI 1978 

Cardio 284 Gastro 284 Hepatic Renal 

284 142 284 M (acute toxic tubular 

nephrosis) 

Endocr 284 Dermal 284 

Reproductive 

58 Rat 

(OsborneMendel) 

78 wk 5 d/wk (GO) 

Bd Wt 284 

108 M 

76 F 

NCI 1978 

59 Mouse 

(B6C3F1) 

78 wk 5 d/wk (GO) 

284 NCI 1978 
792

142

60 

Table 3-2 Levels of Significant Exposure to 1,1,2,2-Tetrachloroethane - Oral (continued) 

Exposure/ LOAEL 

Duration/ 

a 

Key to Species Frequency NOAEL Less Serious Serious Reference 

Figure (Strain) (Route) System (mg/kg/day) (mg/kg/day) (mg/kg/day) Chemical Form 

Cancer 

Mouse 78 wk 142 (CEL: hepatocellular NCI 1978 5 d/wk (B6C3F1) carcinoma) (GO) 

a The number corresponds to entries in Figure 3-2. b Benchmark dose (BMD) analysis of the serum ALT data was used to calculate a benchmark dose limit (BMDL) of 26.6 mg/kg/day. An intermediate-duration oral m(MRL) of 0.3 mg/kg/day was derived by dividing the BMDL by a composite uncertainty factor of 100 (10 for extrapolation from animals to humans and 10 for human ad lib = ad libitum; ALT = alanine aminotransferase; AST = aspartate aminotransferase; Bd Wt = body weight; Cardio = cardiovascular; CEL = cancer effect level; Cnervous system; d = day(s); Endocr = endocrine; (F) = feed; F = Female; (G) = gavage; Gastro = gastrointestinal; gd = gestational day; (GO) = gavage in oil; Hemahr = hour(s); Immuno = immunological; (IN) = ingestion; LD50 = lethal dose, 50% kill; LOAEL = lowest-observed-adverse-effect level; M = male; min = minute(s); mMetab = metabolic; Musc/skel = musculoskeletal; NOAEL = no-observed-adverse-effect level; NS = not specified; occup = occupational; Resp = respiratory; SDH = dehydrogenase; x = time(s); wk = week(s) 
Death 

Respiratory Cardiovascular Gastrointestinal Hepatic Renal Body Weight Neurological Developmental 

Figure 3-2 Levels of Significant Exposure to 1,1,2,2-Tetrachloroethane - Oral 

Acute (≤14 days) 

Systemic 

mg/kg/day 

10000 4 18 18 

36m 

16m 27m

14m 

15m 

3 19 19 19 19 19 1000 26m 38m 

11r 

20r 33r 10r 33r 

2 

7r 8r 

17 17 12r 13r 5r 25m 21r 25m 21r 35m 30r 20r 1 23r 24r 31r 32r 6r 

9r 

21r 23r 24r 31r 32r
	

100
	 34r 

28 

34r 

22r 

29 

37r 

34r 

10 

1,1,2,2-TETRACHLOROETHANE

3. HEALTH EFFECTS

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 

53
Death 

Systemic Respiratory Cardiovascular Gastrointestinal Hematological Musculoskeletal Hepatic Renal Endocrine Dermal Body Weight Neurological Reproductive 

Figure 3-2 Levels of Significant Exposure to 1,1,2,2-Tetrachloroethane - Oral (Continued)

Intermediate (15-364 days) 

Systemic 

mg/kg/day 

10000 

46m 46m 46m 46m 46m 51m 54m
	

1000
	

45m 50m 47m 47m 52m 43r 

43r 

39r 42r 42r 42r 42r 42r 45m 42r 42r 44m 46m

43r 50m 53r

46m 48r

46m 40r 42r 53r 53r

41r 41r 41r 

46m 

42r 

48r 

42r 

100 40r 40r 

42r 49r 53r 

40r 

10 

1 

0.1 

1,1,2,2-TETRACHLOROETHANE

3. HEALTH EFFECTS

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 

54
Death 

Respiratory Cardiovascular Gastrointestinal Hepatic Renal Endocrine Dermal Body Weight Reproductive Cancer * 

 

 

Figure 3-2 Levels of Significant Exposure to 1,1,2,2-Tetrachloroethane - Oral (Continued)
 

Chronic (≥365 days)
	

Systemic 

mg/kg/day 

1000
	

55m 57m 57m 57m 57m 57m 57m 57m 57m 59m 

57m 60m 100
	 56r 56r 56r 56r 56r 56r 56r 58r 56r 58r 56r 56r 56r

10
	

1
	

0.1 

0.01 

0.001
	 -4 10
	

Estimated
	

0.0001
	 Upper-Bound

-5 10
	 Human Cancer 

Risk Levels 

1E-5 

-6 10
	

1E-6 *Doses represent the lowest dose tested per study that produced a tumorigenic
	

response and do not imply the existence of a threshold for the cancer endpoint. 10-7
	

1E-7 

1,1,2,2-TETRACHLOROETHANE

3. HEALTH EFFECTS

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 

55
 

 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 56 

3. HEALTH EFFECTS 

systemic end points in each species and duration category are recorded in Table 3-2 and plotted in 

Figure 3-2. 

Respiratory Effects. Autopsy reports in humans following suicidal ingestion of at least 1,100 mg/kg 

of 1,1,2,2-tetrachloroethane revealed congestion and edema in the lungs (Hepple 1927; Mant 1953), but 

this did not appear to be the primary cause of death. A case of exposure at 9,600 mg/kg was reported to 

have caused lung collapse (Mant 1953). African men and women accidentally given oral doses of 

undiluted 1,1,2,2-tetrachloroethane (approximately 70–117 mg/kg) experienced shallow breathing during 

ensuing unconsciousness (Sherman 1953; Ward 1955). 

Labored respiration, wheezing, and/or nasal discharge were observed in rats administered 1,1,2,2-tetrachloroethane in the diet for 78 weeks at reported TWA doses ranging from 43 to 108 mg/kg/day (NCI 

1978). However, these effects may be at least partially attributable to the development of chronic murine 

pneumonia in controls and treatment groups alike. Mice treated for the same duration at concentrations 

resulting in daily 1,1,2,2-tetrachloroethane doses as high as 284 mg/kg/day experienced no respiratory 

effects (NCI 1978). 

Cardiovascular Effects. African men and women accidentally given oral doses (approximately 70– 

117 mg/kg undiluted) experienced pronounced lowering of blood pressure (to 60/46) and faint pulse 

during ensuing unconsciousness (Sherman 1953; Ward 1955). A lethal oral dose (suicide) of 

1,100 mg/kg produced epicardial and endocardial anoxic hemorrhage (Mant 1953). 

Rats receiving up to 108 mg/kg/day and mice receiving 284 mg/kg/day orally for 78 weeks showed no 

gross or histological alterations of the heart (NCI 1978). 

Gastrointestinal Effects. Single doses of 357 mg/kg or more caused mucosal congestion of the 

esophagus and upper stomach of humans (Lilliman 1949; Mant 1953). Rats receiving up to 

108 mg/kg/day and mice receiving 284 mg/kg/day oral doses for 78 weeks showed no gross or 

microscopic histological alterations of the stomach, colon, pancreas, or bile duct (NCI 1978). 

Hematological Effects. No information was located regarding 1,1,2,2-tetrachloroethane-induced 

hematological effects following oral exposure in humans. 1,1,2,2-Tetrachloroethane did not appear to 

cause hematological effects in male or female rats administered the chemical in the diet for 14 weeks at 

TWA doses as high as 320 mg/kg/day (NTP 2004a). 
 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 57 

3. HEALTH EFFECTS 

Hepatic Effects. Autopsy reports showed no evidence of damage to the livers of humans who 

ingested suicidal doses of 1,1,2,2-tetrachloroethane (Mant 1953). The lack of effect in the liver can be 

ascribed to the rapid lethality. In another autopsy report, slight congestion of the liver was reported from 

an accidental poisoning or suicide attempt with 1,1,2,2-tetrachloroethane (Lilliman 1949). 

Rats administered a single gavage dose of 1,1,2,2-tetrachloroethane had toxicologically significant 

increases (>2-fold greater than controls) in serum AST at ≥574mg/kg and serum ALT at 1,148 mg/kg 

(Cottalasso et al. 1998), but this study is limited by a lack of liver histology examinations; the NOAEL 

was 287 mg/kg. Hepatocellular degeneration occurred in mice exposed to a lethal dietary dose of 

2,394 mg/kg/day for 6 days (NTP 2004a). Rats and mice that were exposed by gavage for 4 days had 

increased liver cell DNA synthesis (as shown by increased incorporation of [3

H]-thymidine) and 

increased mitotic activity at 75–300 mg/kg/day, but the only hepatic histological changes were 

centrilobular swelling and decreased periportal hepatocyte size in the mice at ≥75 mg/kg/day (Hanley et 

al. 1988). Because increased DNA synthesis and mitosis are not necessarily indicative of hepatotoxicity 

and the histological examinations showed no accompanying degenerative or other adverse liver lesions, 

this study identified a NOAEL of 300 mg/kg/day for hepatic effects. Rats that were exposed to a single 

100 mg/kg gavage dose had no clearly adverse changes in serum ALT or other clinical chemistry indices, 

but the study was limited by inadequately reported liver histology data (Schmidt et al. 1980a). This study 

includes a general statement implying that the 100 mg/kg dose induced liver lesions, including necrosis 

and fatty degeneration, but the significance of the statement cannot be assessed because incidences and 

other specific histology data were not reported. These findings are not necessarily inconsistent with the 

lack of degenerative liver lesions in the rats exposed to gavage doses of 75–300 mg/kg/day for 4 days 

(Hanley et al. 1988), because 1,1,2,2-tetrachlorethane could have acted as a suicide substrate (see Section 

3.4.3) in the single dose study (i.e., inactivated the metabolic enzymes needed to activate subsequent 

doses). 

Hepatocellular degeneration was noted in mice exposed to 1,1,2,2-tetrachloroethane at levels of 

599 mg/kg/day in the diet for 15 days (NTP 2004a) or 337.5 mg/kg/day by gavage for 16 days (NTP 

1993d). Exposure to 104 mg/kg/day by gavage for 21 days caused mild to moderate hepatocellular 

cytoplasmic vacuolation in rats (NTP 1996), but no degenerative or other liver lesions. Hepatic effects in 

rats receiving 1,1,2,2-tetrachloroethane in the diet for 14 weeks included increases in hepatic cytoplasmic 

vacuolization at 20 mg/kg/day (lowest tested dose), liver weight at 40 mg/kg/day, and hepatocellular 

hypertrophy at 80 mg/kg/day (NTP 2004a). These hepatic effects are not considered adverse because the 
 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 58 

3. HEALTH EFFECTS 

severity of the vacuolation was minimal to mild and did not increase with dose, and the increases in liver 

weight and hepatocellular hypertrophy are considered adaptive responses to chemical exposure. Increases 

in serum ALT and SDH and decreases in serum cholesterol also occurred at ≥80mg/kg/day, but the 

magnitudes of these changes were biologically significant only at 170 and 320 mg/kg/day. Other effects 

that occurred at 170 and 320 mg/kg/day included increases in serum ALP and bile acids, hepatocyte 

necrosis, bile duct hyperplasia, hepatocellular mitotic alterations, foci of cellular alterations, and liver 

pigmentation. This 14-week rat study (NTP 2004a) identified a NOAEL of 80 mg/kg/day and a LOAEL 

of 170 mg/kg/day based on adverse liver-related serum chemistry changes and histological manifestations 

of hepatocellular damage and was used as the basis for deriving an intermediate-duration oral MRL for 

1,1,2,2-tetrachloroethane. NTP (2004a) similarly exposed mice to 1,1,2,2-tetrachloroethane in the diet for 

14 weeks. Effects in the mice included minimal hepatocellular hypertrophy, increases in serum SDH, 

ALT, and bile acids, and decreased serum cholesterol at 160–200 mg/kg/day, but the magnitudes of these 

changes were biologically significant only at 300–370 mg/kg/day. Other effects that occurred in the mice 

at 300–370 mg/kg/day included increases in serum ALP and 5’-nucleotidase, necrosis, pigmentation, and 

bile duct hyperplasia. Based on the adverse serum chemistry and histopathological changes at 

300 mg/kg/day and higher doses, this study identified a NOAEL of 200 mg/kg/day and a LOAEL of 

300 mg/kg/day for liver toxicity in mice. 

In the only chronic oral study, gavage exposure to 108 mg/kg/day for 78 weeks caused fatty degeneration 

in the liver of rats (NCI 1978). Interpretation of the results is confounded by high incidences of endemic 

chronic murine pneumonia, but this is unlikely to have contributed to effects observed in the liver. 

Renal Effects. Autopsy reports showed no evidence of damage to the kidney of humans who ingested 

suicidal doses of 1,1,2,2-tetrachloroethane (Mant 1953). The lack of effect can be ascribed to the rapid 

lethality. No other studies were located regarding renal effects in humans following oral exposure to 

1,1,2,2-tetrachloroethane. 

No treatment-related renal effects were seen in rats or mice administered 1,1,2,2-tetrachloroethane in the 

diet for 14 weeks at concentrations resulting in doses as high as 320 and 1,400 mg/kg/day, respectively 

(NTP 2004a). In studies conducted by the NCI (1978), rats treated with up to 108 mg/kg/day for 

78 weeks showed no gross or histopathological changes in the kidney. Mice treated for the same duration 

at 142 mg/kg/day also showed no changes, but at 284 mg/kg/day, toxic tubular nephrosis was determined 

to be the probable cause of death in male mice. However, this renal effect may have been secondary to 

hepatocellular carcinoma noted in most of these high-dose (284 mg/kg/day) male mice. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 59 

3. HEALTH EFFECTS 

Endocrine Effects. No studies were located regarding endocrine effects in humans after oral 

exposure to 1,1,2,2-tetrachloroethane. No treatment-related histopathological effects were seen in major 

endocrine tissues, including pituitary, thyroid, parathyroid, and adrenals of rats or mice administered 

1,1,2,2-tetrachloroethane in the diet for 14 weeks at concentrations resulting in doses as high as 320 and 

1,400 mg/kg/day, respectively (NTP 2004a) or in other rats or mice chronically administered the chemical 

(5 days/week for 78 weeks) via oral gavage at doses as high as 108 and 284 mg/kg/day, respectively (NCI 

1978). 

Dermal Effects. No studies were located regarding dermal effects in humans after oral exposure to 

1,1,2,2-tetrachloroethane. No changes were noted in the gross appearance of skin or subcutaneous tissues 

in rats or mice exposed to 1,1,2,2-tetrachloroethane at doses up to 284 mg/kg/day for 78 weeks (NCI 

1978). 

Ocular Effects. No studies were located regarding ocular effects in humans after oral exposure to 

1,1,2,2-tetrachloroethane. Squinted or reddened eyes with a reddish-brown discharge were noted in male 

and female rats at all dose levels treated with 1,1,2,2-tetrachloroethane for 78 weeks (NCI 1978). 

Body Weight Effects. No studies were located regarding body weight effects in humans after oral 

exposure to 1,1,2,2-tetrachloroethane. 

No treatment-related effects on body weight were seen in rats administered 1,1,2,2-tetrachloroethane in 

daily gavage doses up to 104 mg/kg for 21 days (NTP 1996). In a study that employed higher dose 

levels, oral gavage administration of 1,1,2,2-tetrachloroethane for 3–14 days in the range of 270– 

300 mg/kg/day resulted in body weights that were 17–55% lower than controls; no adverse body weight 

effects were seen at the lower doses ranging from 135 to 150 mg/kg/day (Hanley et al. 1988; NTP 1993a, 

1993b). No adverse body weight effects were seen in mice administered 1,1,2,2-tetrachloroethane via 

oral gavage at doses as high as 300 mg/kg/day for 4 days (Hanley et al. 1988) or other mice receiving up 

to 1,350 mg/kg/day for 12 of 16 days (NTP 1993d). Daily doses of 178 mg/kg/day, 5 days/week for 

6 weeks resulted in 38–41% depressed body weight gains in male and female rats, relative to controls; at 

100 mg/kg/day, respective body weight gains were 9 and 24% less than controls (NCI 1978). In contrast, 

no effects on body weight gain were seen in mice similarly exposed at doses as high as 316 mg/kg/day. 
 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 60 

3. HEALTH EFFECTS 

Similar effect levels were reported following dietary exposure. A dietary concentration resulting in a 

daily dose of 300 mg/kg for 15 days resulted in a 25–29% depressed final body weights in rats (NTP 

2004a). In a 14-week dietary study in rats, concentrations of 1,1,2,2-tetrachloroethane resulting in a dose 

level of 170 mg/kg/day caused a 29% depression in final body weight; at a dose level of 320 mg/kg/day, 

actual body weight loss was noted (NTP 2004a). In mice, dosing at 599 mg/kg/day for 15 days resulted 

in a 10–14% depressed final body weight (NTP 2004a). A 12% depression in final body weight was 

noted in mice receiving 370 mg/kg/day for 14 weeks; the 200 mg/kg/day level did not elicit treatmentrelated body weight effects (NTP 2004a). Approximately 14–18% depressed body weight was noted in 

male and female rats administered 1,1,2,2-tetrachloroethane via oral gavage at doses of 108 and 

76 mg/kg/day, respectively; no body weight effects were seen at the lower dose (62 and 43 mg/kg/day in 

males and females, respectively) (NCI 1978). No treatment-related adverse body weight effects were 

elicited by similar treatment of male and female mice for 78 weeks at doses of 142 or 284 mg/kg/day 

(NCI 1978). 

3.2.2.3 Immunological and Lymphoreticular Effects 

One investigator reported that the results of an autopsy showed an enlarged and congested spleen in a 

case of intentional or accidental ingestion of 1,1,2,2-tetrachloroethane (Hepple 1927), while another 

autopsy study reported that the gross appearance of the spleen was normal (Elliott 1933). 

Limited information is available regarding the potential for 1,1,2,2-tetrachloroethane-induced 

immunological or lymphoreticular effects following oral exposure. In a 14-week dietary study of rats, 

pigmentation of the spleen was increased in males receiving 1,1,2,2-tetrachloroethane at doses of 

≥80 mg/kg/day and in females receiving doses of ≥170 mg/kg/day; high incidences (70–100%) of atrophy 

in the spleen (red pulp and lymphoid follicle) of both sexes were noted at 320 mg/kg/day (NTP 2004a). 

Relative thymus weights were reduced in rats that were exposed to 400 mg/kg/day for 15 days or 

320 mg/kg/day for 14 weeks, and in mice exposed to 599 mg/kg/day for 15 days (NTP 2004a). No gross 

or histological alterations were seen in the spleen or lymph nodes of rats and mice exposed to 

1,1,2,2-tetrachloroethane for 78 weeks at doses up to 108 and 284 mg/kg/day, respectively (NCI 1978). 
 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 61 

3. HEALTH EFFECTS 

3.2.2.4 Neurological Effects 

Information on the neurotoxicity of oral exposure to 1,1,2,2-tetrachloroethane in humans is available from 

several case reports. People who intentionally ingested lethal amounts usually lost consciousness within 

approximately 1 hour and died 3–20 hours postingestion (Elliott 1933; Forbes 1943; Hepple 1927; 

Lilliman 1949; Mant 1953; Sherman 1953). Patients who were accidentally given an estimated oral dose 

of 68–118 mg/kg as medicinal treatment for hookworm experienced loss of consciousness and other 

clinical signs of narcosis that included shallow breathing, faint pulse, and pronounced lowering of blood 

pressure (Sherman 1953; Ward 1955). In animals, lethargy and central nervous system depression 

occurred in rats gavaged with 270–300 mg/kg/day for 1–12 days (Hanley et al. 1988; NTP 1993a, 1993b) 

or 208 mg/kg/day for 21 days (NTP 1996). Information on neurological effects of lower acute oral doses 

is limited to a rat study in which a single gavage dose of 100 mg/kg caused ataxia and 50 mg/kg caused 

decreased passive avoidance to an electric shock, possibly due to an increased threshold of shock 

perception due to a subtle anesthetic effect (Wolff 1978). Evaluation of this study is complicated by 

incomplete reporting and insufficient quantitative data, but the possible anesthetic effect suggests that 

50 mg/kg is a LOAEL for neurotoxicity in rats. The LOAEL values for each reliable study for 

neurological effects after acute-duration exposure are recorded in Table 3-2 and plotted in Figure 3-2. 

3.2.2.5 Reproductive Effects 

No studies were located regarding reproductive effects in humans following oral exposure to 1,1,2,2-tetrachloroethane. No gross or histological alterations in the reproductive organs of male or female rats or 

mice administered 1,1,2,2-tetrachloroethane by oral gavage 5 days/week for 78 weeks at doses as high as 

108 and 76 mg/kg/day in male and female rats, respectively, and 284 mg/kg/day in mice (NCI 1978). 

Atrophy of prostate gland, seminal vesicle, and testicular germinal epithelium was noted in male rats 

administered 1,1,2,2-tetrachloroethane in the diet for 14 weeks at a concentration resulting in a dose level 

of 320 mg/kg/day; similar treatment of female rats at a dose level of 170 mg/kg/day resulted in uterine 

atrophy and changes in lengths of estrus cycle stages (NTP 2004a). 

The highest NOAEL and all LOAEL values from all reliable studies for reproductive effects in each 

species and duration category are recorded in Table 3-2 and plotted in Figure 3-2. 
 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 62 

3. HEALTH EFFECTS 

3.2.2.6 Developmental Effects 

No studies were located regarding developmental effects in humans following oral exposure to 

1,1,2,2-tetrachloroethane. In a developmental toxicity report submitted to NTP (1991a), no changes in 

numbers of live fetuses per litter, dead fetuses per litter, resorptions per litter, or implants per litter were 

seen following dietary exposure of pregnant rats to 1,1,2,2-tetrachloroethane during gestation days 6–16 

at maternal doses ranging from 34 to 330 mg/kg/day. One dam in the 98 mg/kg/day group and four of 

nine dams in the 330 mg/kg/day group completely resorbed their litters. At scheduled sacrifice, average 

fetal weights were statistically significantly decreased in all dose groups except the 34 mg/kg/day group 

(4.9, 4, 12.8, 10.6, and 20.7% decrease in the 34, 98, 180, 278, and 330 mg/kg/day groups, respectively). 

However, in this study, 1,1,2,2-tetrachloroethane treatment resulted in dose-related significantly 

decreased maternal body weight (9.3, 11.6, 13.8, and 24% lower than controls in the 98, 180, 278, and 

330 mg/kg/day groups, respectively) and dose-related decreased food consumption ranging in magnitude 

from 16 to 60% less than that of controls. Because complete resorptions occurred only at doses resulting 

in significantly reduced food consumption and serious maternal body weight effects, the results of this 

developmental toxicity study (NTP 1991a) are not included in Table 3-2 or Figure 3-2. In a similar study 

report of dietary exposure of pregnant mice (NTP 1991b), the lowest exposure level (0.5% in the food; 

dose of approximately 987 mg/kg/day) resulted in 14% decreased maternal body weight gain during the 

treatment period, but no indications of developmental effects with respect to number of implantation sites, 

number of resorptions, numbers of dead and live fetuses, or gravid uterine weight. Exposure at higher 

levels resulted in maternal death, precluding assessment of treatment-related developmental toxicity at the 

higher doses. 

3.2.2.7 Cancer 

No studies were located regarding carcinogenic effects in humans following oral exposure to 

1,1,2,2-tetrachloroethane. 

A study in humans evaluated the possible carcinogenic effects of 1,1,2,2-tetrachloroethane in clothingtreatment workers (Norman et al. 1981). Inhalation exposure concentrations and durations were not 

reported, and coexposures to other chemicals and dermal exposures were likely. No increases in standard 

mortality ratios were found for total mortality, cardiovascular disease, cirrhosis of the liver, or cancer of 

the digestive and respiratory systems. The mortality ratio for lymphatic cancers was increased, although 

the number of deaths was small (4 cases observed compared to 0.85 expected). 
 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 63 

3. HEALTH EFFECTS 

Carcinogenicity of 1,1,2,2-tetrachloroethane in animals was evaluated in chronic oral studies in rats and 

mice (NCI 1978). The purity of the 1,1,2,2-tetrachloroethane was approximately 90% (contaminants not 

identified). Male and female rats were exposed to time-weighted average (TWA) doses of 0, 62, or 

108 mg/kg/day (males) or 0, 43, or 76 mg/kg/day (females) by gavage 5 days/week for 78 weeks, 

followed by a 32-week period during which the rats were not exposed. There was a high prevalence of 

endemic chronic murine pneumonia in both sexes that likely contributed to early mortality that occurred 

in 20% of the females. No significant increases in tumor incidences were observed in the rats. Male and 

female B6C3F1 mice were similarly exposed to TWA doses of 0, 142, or 284 mg/kg/day for 78 weeks, 

followed by a 12-week period during which the mice were not exposed. Survival was markedly 

decreased after 45 weeks of exposure in the high-dose male and female mice; the cause of death appeared 

to be acute toxic tubular nephrosis in the males but was not reported in the females. Significant, doserelated increases in the incidence of hepatocellular carcinoma were observed in the male mice (3/36, 

13/50, and 44/49 in the control, low-dose, and high-dose groups, respectively) and female mice (1/40, 

30/48, and 43/47, respectively). 

The EPA has classified the carcinogenicity of 1,1,2,2-tetrachloroethane as Group C, possible human 

carcinogen (IRIS 2006). The EPA (IRIS 2006) calculated an oral slope factor of 0.2 (mg/kg/day)-1 for 

1,1,2,2-tetrachloroethane (verified June 26, 1986), based on the NCI (1978) study showing increased 

hepatocellular carcinomas in female mice. This q1* corresponds to upper bound individual lifetime 

cancer risks ranging from 5x10-4 mg/

kg/day (10-4 risk level) to 5x10-7 mg/kg/day (10-7 risk level). These 

risk levels are indicated on Figure 3-2. 

3.2.3 Dermal Exposure 

3.2.3.1 Death 

One human death was reported when a man cleaned up a 1,1,2,2-tetrachloroethane spill with his bare 

hands (Coyer 1944). He was also exposed to unmeasured levels of 1,1,2,2-tetrachloroethane vapors. 

The dermal LD50 (lethal dose, 50% kill) for 1,1,2,2-tetrachloroethane in rabbits is 6,360 mg/kg (Smyth et 

al. 1969). 
 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 64 

3. HEALTH EFFECTS 

3.2.3.2 Systemic Effects 

Since humans dermally exposed to 1,1,2,2-tetrachloroethane invariably were reported to have 

considerable inhalation exposure as well, separation of effects due solely to dermal exposure could not be 

determined. Those exposed to 1,1,2,2-tetrachloroethane in the workplace showed cardiovascular, gastric, 

hematological, and hepatic disturbances as noted in the discussion on systemic effects due to inhalation 

exposure discussed in Section 2.2.1.2 (Coyer 1944; Lobo-Mendonca 1963; Minot and Smith 1921). Total 

exposure levels and effects due to inhalation versus dermal exposure were not determined in these studies, 

but air concentrations were reported to vary from 9 to 98 ppm in one study (Lobo-Mendonca 1963). 

No studies were located regarding respiratory, cardiovascular, gastrointestinal, hematological, 

musculoskeletal, hepatic, and renal effects in animals after dermal exposure to 1,1,2,2-tetrachloroethane. 

Dermal Effects. Direct application of 514 mg/cm2 of 1,1,2,2-tetrachloroethane for 16 hours damaged 

the skin of guinea pigs, causing karyopyknosis and pseudoeosinophilic infiltration (Kronevi et al. 1981). 

Application of 1,1,2,2-tetrachloroethane (concentration not reported) to the shaved abdomen of rabbits 

caused hyperemia, edema, and severe blistering (Dow 1944). Smyth et al. (1969) similarly found that 

application of 1,1,2,2-tetrachloroethane to the uncovered abdomen of rabbits caused local skin irritation 

(severity of 6 on a scale of 1–10). 

Ocular Effects. Humans exposed to 1,1,2,2-tetrachloroethane vapors (130 ppm) for 10 minutes 

experienced mucosal irritation around the eyes (Lehmann and Schmidt-Kehl 1936). Similarly, guinea 

pigs exposed to 576 ppm for 5 minutes demonstrated eye closure and squinting; by 15 minutes, 

lacrimation was common (NIOSH 1978). Rats showed these effects at 5,050 ppm. These ocular effects 

are due to direct contact of the eyes with the vapors rather than a true systemic effect due to inhalation of 

the vapor. No studies were located in which liquid 1,1,2,2-tetrachloroethane was instilled directly into the 

eye. 

3.2.3.3 Immunological and Lymphoreticular Effects 

Data on the immunological and lymphoreticular effects in humans and animals following dermal 

exposure are limited. One person who died following dermal exposure to 1,1,2,2-tetrachloroethane had 

an enlarged spleen with nodular areas on its surface (Coyer 1944). This individual cleaned up a spill with 

his bare hands, and the nature and extent of the exposure were poorly defined. 
 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 65 

3. HEALTH EFFECTS 

No dermal hypersensitivity tests in guinea pigs or other kinds of studies were located regarding 

immunological or lymphoreticular effects in animals after dermal exposure to 1,1,2,2-tetrachloroethane. 

3.2.3.4 Neurological Effects 

Workers in India's bangle industry who dipped their hands into 1,1,2,2-tetrachloroethane and inhaled it 

had tremors and vertigo in addition to gastric disturbances (Lobo-Mendonca 1963). Specific exposure 

levels were not measured, but air concentrations were measured at between 9 and 98 ppm. The incidence 

of tremors was higher among factory workers exposed to higher concentrations, suggesting a doseresponse relationship. Workers in an artificial silk plant experienced fatigue, irritability, headache, and 

coma (Minot and Smith 1921). Exposure levels were not estimated. 

No studies were located regarding neurological effects in animals following dermal application of 

1,1,2,2-tetrachloroethane. 

No studies were located regarding the following effects in humans or animals following dermal exposure 

to 1,1,2,2-tetrachloroethane: 

3.2.3.5 Reproductive Effects 

3.2.3.6 Developmental Effects 

3.2.3.7 Cancer 

3.3 GENOTOXICITY 

No studies were located regarding genotoxic effects in humans following inhalation, oral, or dermal 

exposure to 1,1,2,2-tetrachloroethane. In vitro and in vivo tests of genotoxicity of 1,1,2,2-tetrachloroethane have produced mixed results, as discussed below and summarized in Tables 3-3 and 3-4. 

1,1,2,2-Tetrachloroethane has been shown to be predominantly inactive in reverse mutation assays in 

Salmonella typhimurium (strains TA97, TA98, TA100, TA1530, TA1535, TA1537, and TA1538), either 

with or without the addition of S9 metabolic activating mixture, even at concentrations that lead to 
 

1,1,2,2-TETRACHLOROETHANE 66 

3. HEALTH EFFECTS 

Table 3-3. Genotoxicity of 1,1,2,2-Tetrachloroethane In Vitro 

Results 

Species With Without 

(test system) End point activation activation References 

Salmonella 

typhimurium 

Saccharomyces 

cerevisiae 

Escherichia coli 

Aspergillus nidulans 

L5178Y mouse 

lymphoma cells 

Chinese hamster 

ovary cells 

Chinese hamster 

ovary cells 

BALB/c 3T3 mouse 

cells 

Rat hepatocytes 

Mouse hepatocytes 

Human embryonic 

intestinal cells 

Reverse mutation 

Forward mutation 

Gene mutation 

DNA growth, repair, or 

synthesis 

Mitotic cross-over 

Aneuploidy 

Gene mutation 

Chromosomal aberrations 

Sister chromatid 

exchange 

Sister chromatid 

exchange 

Cell transformation 

Promotion of cell 

transformation 

DNA growth, repair, or 

synthesis 

DNA growth, repair, or 

synthesis 

DNA growth, repair, or 

synthesis 

– 

–a 

a,b –

–c 

– 

–a 

–a 

Not tested 

Not tested 

+d 

b –

Not tested 

Not tested 

Not tested 

Not tested 

+d 

Not tested 

Not tested 

b –

b –

b –

+b 

+b 

+b 

Not tested 

Not tested 

–a 

+b 

Not tested 

Not tested 

Not tested 

Not tested 

Not tested 

– 

– 

–a 

a,b –

–c 

– 

–a 

–a 

+a,c 

+a,c 

+d 

b –

+b 

– 

+a,d 

+a,d 

d –

b –

+b 

b –

b –

b –

+b 

+b 

+b 

a,b –

a,b –

–a 

+b 

b –

a,b –

a,b –

a,b –

a,b –

Not tested 

Haworth et al. 1983 

Milman et al. 1988 

Nestmann et al. 1980 

NTP 2004a 

Ono et al. 1996 

Mitoma et al. 1984 

Warner et al. 1988 

Brem et al. 1974 

Rosenkranz 1977 

Strobel and Grummt 1987 

Roldan-Arjona et al. 1991 

Callen et al. 1980 

Nestmann and Lee 1983 

Brem et al. 1974 

Rosenkranz 1977 

DeMarini and Brooks, 1992 

Crebelli et al. 1988 

Crebelli et al. 1988 

NTP 2004a 

Galloway et al. 1987 

NTP 2004a 

Galloway et al. 1987 

NTP 2004a 

Colacci et al. 1992 

Arthur D. Little Inc. 1983 

Tu et al. 1985 

Milman et al. 1988 

Colacci et al. 1990 

Colacci et al. 1996 

Milman et al. 1988 

Naylor Dana Institute 1983 

Milman et al. 1988 

Naylor Dana Institute 1983 

NIOSH 1980 

a

Adjusted for volatility

b

Tested up to cytotoxic concentrations 

c

Not adjusted for volatility d

Cytotoxic concentrations not included 

– = negative result; + = positive result 
 

1,1,2,2-TETRACHLOROETHANE 67 

3. HEALTH EFFECTS 

Table 3-4. Genotoxicity of 1,1,2,2-Tetrachloroethane In Vivo 

Species/test system End point	 Result Reference 

Drosophila melanogaster Sex-linked recessive lethal mutation –	 NIOSH 1980; NTP 

2004a; Woodruff et al. 

1985 

Mitotic recombination – Vogel and Nivard 1993 

Mouse hepatocytes Unscheduled DNA synthesis + Miyagawa et al. 1995 

Mouse hepatocytes, male Unscheduled DNA synthesis – Mirsalis et al. 1989 

S-Phase DNA synthesis – Mirsalis et al. 1989 

Mouse hepatocytes, female Unscheduled DNA synthesis – Mirsalis et al. 1989 

S-Phase DNA synthesis +/– Mirsalis et al. 1989 

Rat bone marrow cells, male Chromosomal aberrations – NIOSH 1980 

Rat bone marrow cells, female Chromosomal aberrations + NIOSH 1980 

Mouse peripheral blood Micronucleus formation + NTP 2004a 

erythrocytes 

+ = active; – = inactive; +/– = equivocal 
 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 68 

3. HEALTH EFFECTS 

cytotoxicity (Haworth et al. 1983; Milman et al. 1988; Mitoma et al. 1984; Nestmann et al. 1980; NTP 

2004a; Ono et al. 1996; Warner et al. 1988). However, a few studies reported reverse mutation activity in 

S. typhimurium (Brem et al. 1974; Rosenkranz 1977; Strobel and Grummt 1987). Results of studies 

employing methods to prevent volatilization were not notably different from those that did not use those 

methods. 1,1,2,2-Tetrachloroethane also did not induce forward mutations (L-arabinose resistance) in 

S. typhimurium strain BA13 (Roldan-Arjona et al. 1991). Assays with Escherichia coli indicated that 

1,1,2,2-tetrachloroethane induced DNA damage, as shown by growth inhibition in DNA polymerase 

deficient E. coli (Brem et al. 1974; Rosenkranz 1977) and induction of prophage lambda (DeMarini and 

Brooks 1992). In Saccharomyces cerevisiae, 1,1,2,2-tetrachloroethane induced gene conversion, 

reversion, and recombination in one study (Callen et al. 1980), whereas another study found no 

conversion or reversion (Nestmann and Lee 1983). In Aspergillus nidulans, 1,1,2,2-tetrachloroethane 

induced aneuploidy, but no crossing over (Crebelli et al. 1988). 

1,1,2,2-Tetrachloroethane did not induce trifluorothymidine resistance in L5178Y mouse lymphoma cells, 

with or without S9, at concentrations up to those producing lethality (NTP 2004a). Primary hepatocytes 

from rats and mice exposed in vitro to 1,1,2,2-tetrachloroethane did not show altered DNA repair at 

concentrations that were not cytotoxic (Milman et al. 1988; Naylor Dana Institute 1983). NIOSH (1980) 

reported no increase in unscheduled DNA synthesis (UDS) in human embryonic intestinal fibroblasts 

exposed to 1,1,2,2-tetrachloroethane. Treatment of Chinese hamster ovary (CHO) cells with up to 

653 μg/mL (which was cytotoxic) did not result in increased induction of chromosomal aberrations, but 

did produce an increased frequency of sister chromatid exchanges (SCEs) at concentrations of 

55.8 μg/mL or higher (Galloway et al. 1987; NTP 2004a). SCEs were also induced in BALB/c-3T3 cells 

treated in vitro with high concentrations (500 μg/mL or higher) of 1,1,2,2-tetrachloroethane, either with or 

without S9 activating mixture (Colacci et al. 1992). 

In BALB/c-3T3 cells, 1,1,2,2-tetrachloroethane exposure of up to 250 μg/mL in the absence of exogenous 

metabolic activation did not result in increased numbers of transformed cells (Arthur D. Little Inc. 1983; 

Colacci et al. 1992; Milman et al. 1988; Tu et al. 1985); survival was generally 70% or higher. Higher 

doses (500 μg/mL or more) were capable of transforming the cells, but also showed higher levels of 

cytotoxicity (Colacci et al. 1990). In the presence of exogenous metabolic activation, however, even 

relatively low levels (31.25 μg/mL) of 1,1,2,2-tetrachloroethane used as an initiating agent, followed by 

promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA), resulted in increased numbers of 

transformed cells (Colacci et al. 1992). 1,1,2,2-Tetrachloroethane did not act as a promoter in 

BALB/c-3T3 cells in vitro without metabolic activation (Colacci et al. 1996). 
 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 69 

3. HEALTH EFFECTS 

1,1,2,2-Tetrachloroethane tested negative for sex-linked recessive lethal mutations and mitotic 

recombination in Drosophila melanogaster (NIOSH 1980; NTP 2004a; Vogel and Nivard 1993; 

Woodruff et al. 1985). Replicative DNA synthesis was increased in hepatocytes isolated from male 

B6C3F1 mice exposed to a single gavage dose of 200 mg/kg (24 and 48 hours postexposure) or 

400 mg/kg (24, 39, and 48 hours postexposure) relative to hepatocytes from unexposed mice (Miyagawa 

et al. 1995). Hepatocytes isolated from mice following a single gavage dose of up to 1,000 mg/kg did not 

show an increase in UDS or S-phase DNA synthesis (Mirsalis et al. 1989). Inhalation exposure to 5 or 

50 ppm (34.3 or 343 mg/m3

) for 7 hours/day, 5 days/week did not result in increased frequency of 

chromosomal aberrations in bone marrow cells isolated from male rats (NIOSH 1980); female rats 

exposed to 50 ppm (343 mg/m3

), but not to 5 ppm (34.3 mg/m3), showed an increase in bone marrow cell 

aberrations other than gaps (NIOSH 1980). Covalent binding of radiolabeled 1,1,2,2-tetrachloroethane to 

DNA, ribonucleic acid (RNA), and protein in the liver, kidney, lung, and stomach occurred in rats and 

mice exposed to a single intravenous dose and analyzed 22 hours postexposure (Colacci et al. 1987). 

3.4 TOXICOKINETICS 

In both humans and laboratory animals, 1,1,2,2-tetrachloroethane is well absorbed from the respiratory 

and gastrointestinal tracts, and is absorbed through the skin of animals after dermal exposure. When 

administered by oral or inhalation routes, 1,1,2,2-tetrachloroethane is extensively metabolized and 

excreted chiefly as metabolites in the urine and breath. In rats and mice, 1,1,2,2-tetrachloroethane is 

metabolized to trichloroethanol, trichloroacetic acid, and dichloroacetic acid, which is then broken down 

to glyoxylic acid, oxalic acid, and carbon dioxide; a small percentage of the dose is expired in the breath 

as the parent compound and as carbon dioxide. In reductive and oxidative metabolism, 1,1,2,2-tetrachloroethane is known to produce reactive radical and acid chloride intermediates, respectively. 

3.4.1 Absorption 

3.4.1.1 Inhalation Exposure 

While studies of the systemic toxicity of 1,1,2,2-tetrachloroethane following inhalation in humans are 

indicative of some level of systemic absorption, comparatively few studies have quantitatively addressed 

this issue. A study in volunteers was carried out in which a bulb containing [38Cl]-labeled 1,1,2,2-tetrachloroethane was inserted into their mouths; they immediately inhaled deeply, held their breaths for 
 

 

 

 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 70 

3. HEALTH EFFECTS 

20 seconds, and then exhaled through a trap containing granulated charcoal. The study showed that 97% 

of a single breath of 1,1,2,2-tetrachloroethane was absorbed systemically (Morgan et al. 1970). The 

accuracy of this value is unclear because the procedure used to measure uptake is unorthodox and high 

retention of volatile organic compounds on the charcoal was not validated. Additionally, there were other 

potential sources of 1,1,2,2-tetrachloroethane loss and inexact measurements (e.g., volume of air exhaled 

across the trap) that could affect the results. Two subjects were reported to retain approximately 40–60% 

of inspired 1,1,2,2-tetrachloroethane after a 30-minute exposure of up to 2,300 mg/m3 (Lehmann and 

Schmidt-Kehl 1936), but additional details were not provided. 

The total body burden of radioactivity in male Osborne-Mendel rats and B6C3F1 mice exposed to 

10 ppm (68.7 mg/m3

) of 14C-1,1,2,2-tetrachloroethane vapor for 6 hours (Hanley et al. 1988) was 

38.7 μmol equivalents per kg in rats (9.50 μmol equivalents and using a body weight of 245 g from the 

study) and 127 μmol equivalents per kg in mice (3.059 μmol equivalents and using a body weight of

24.1 g from the study), indicating that the mice absorbed proportionally more 1,1,2,2-tetrachloroethane on 

a per-body-weight basis. Between 92 and 98% of the body burdens were recovered as metabolites, 

indicating that very high uptake of the 10 ppm exposure occurred in both species. Ikeda and Ohtsuji 

(1972) detected metabolites in the urine of rats exposed to 200 ppm (1,370 mg/m3

) of 1,1,2,2-tetrachloroethane, indicating that absorption had occurred, but did not provide a quantitative estimate of absorption 

rate or fraction. Similarly, Gargas and Andersen (1989) followed the elimination of 1,1,2,2-tetrachloroethane from the blood after a 6-hour exposure to 350 ppm (2,400 mg/m3

), but did not provide quantitative 

estimates of absorption. 

3.4.1.2 Oral Exposure 

Studies that quantify absorption following oral exposure in humans were not available. The profound 

effect of ingestion of large amounts of 1,1,2,2-tetrachloroethane indicates that appreciable amounts are 

absorbed. 

Observations in animals also indicate that the oral absorption of 1,1,2,2-tetrachloroethane is rapid and 

extensive. Cottalasso et al. (1998) reported hepatic effects only 15–30 minutes following a single oral 

exposure in rats. Following a single oral exposure of male Osborne-Mendel rats and B6C3F1 mice to 

150 mg/kg of radiolabeled 1,1,2,2-tetrachloroethane in corn oil, only 4–6% of the activity was recovered 

in the feces 72 hours postexposure, while >90% of the administered activity was found in both species as 

metabolites, indicating that the compound was nearly completely absorbed in both rats and mice within 
 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 71 

3. HEALTH EFFECTS 

72 hours (Hanley et al. 1988). Mitoma et al. (1985) exposed groups of male Osborne-Mendel rats to 

25 or 100 mg/kg and B6C3F1 mice to 50 or 200 mg/kg of 1,1,2,2-tetrachloroethane, 5 days/week for 

4 weeks followed by a single radiolabeled dose of the compound, and evaluated its disposition over the 

next 48 hours. While absorption was not quantified, 79% of the dose was metabolized in rats and 68% 

was metabolized in mice, suggesting that at least those levels of compound had been absorbed within 

48 hours. In an abstract, Milman et al. (1984) noted that rats and mice that received 1,1,2,2-tetrachloroethane orally absorbed most of the dose; no further details were available on this study. 

3.4.1.3 Dermal Exposure 

No studies were located regarding absorption following dermal exposure in humans. 

Up to 1 mL of 1,1,2,2-tetrachloroethane applied to the skin of mice or guinea pigs was absorbed within a 

half hour (dose site sealed to prevent evaporation) (Jakobson et al. 1982; Tsuruta 1975). 

3.4.2 Distribution 

No studies were located regarding distribution in humans following inhalation, oral, or dermal exposure 

to 1,1,2,2-tetrachloroethane. 

Following absorption in animals, 1,1,2,2-tetrachloroethane appears to be distributed throughout the body, 

but may selectively accumulate to a degree in certain cells and tissues. The human blood-air partition 

coefficient for 1,1,2,2-tetrachloroethane has been reported to be in the range of 72.6–116 (Gargas et al. 

1989; Meulenberg and Vijverberg 2000; Morgan et al. 1970). The large blood-air partition coefficient 

contributes to low exhaled breath concentrations of unmetabolized 1,1,2,2-tetrachloroethane 

(Section 3.4.4). Although 1,1,2,2-tetrachloroethane is well metabolized (Section 3.4.3), the fraction that 

is metabolized would be less if the blood-air partition coefficient was less. The tissue:air partition 

coefficients for 1,1,2,2-tetrachloroethane in rats have been reported to be 142 (blood), 3,767 (fat), 

196 (liver), and 101 (muscle) (Gargas et al. 1989), indicating that 1,1,2,2-tetrachloroethane is likely to 

partition into fatty tissues, consistent with its low water solubility. 

A high level of hepatic protein-binding radioactivity was seen in mice administered 1,1,2,2-tetrachloroethane by gavage, followed by a single dose of 14C-1,1,2,2-tetrachloroethane. The amount of 
 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 72 

3. HEALTH EFFECTS 

1,1,2,2-tetrachloroethane-derived radioactivity covalently bound to liver protein was about 2 times that 

seen in rats (Mitoma et al. 1985). The difference in toxicity of 1,1,2,2-tetrachloroethane in rats and mice 

may well be due to the higher metabolic rate in mice. 

Following a single intravenous injection of radiolabeled 1,1,2,2-tetrachloroethane, Eriksson and Brittebo 

(1991) reported that a high and selective uptake of nonvolatile radioactivity occurred in the mucosal 

tissues of olfactory and tracheobronchial regions of the respiratory tract and in the mucosae of the oral 

cavity, tongue, nasopharynx, esophagus, and cardiac region of the forestomach. High levels of activity 

were also found in the liver, bile, inner zone of the adrenal cortex, and interstitium of the testis, although 

the levels were not quantified. 

3.4.3 Metabolism 

No studies were located regarding metabolism of 1,1,2,2-tetrachloroethane in humans following 

inhalation, oral, or dermal exposure. 

Information regarding 1,1,2,2-tetrachloroethane metabolism in animals is summarized below, and a 

metabolic scheme based on in vivo and in vitro data in rodents is presented in Figure 3-3. In vivo and 

in vitro studies indicate that the metabolism of 1,1,2,2-tetrachloroethane proceeds via multiple pathways 

in rodents (Casciola and Ivanetich 1984; Halpert 1982; Halpert and Neal 1981; Ikeda and Ohtsuji 1972; 

Koizumi et al. 1982; Mitoma et al. 1985; Yllner 1971). The predominant pathway appears to involve 

production of dichloroacetic acid, formed as an initial metabolite via stagewise hydrolytic cleavage of 

1,1,2,2-tetrachloroethane (nonenzymatic degradation yielding dichloroacetyl chloride and dichloroacetaldehyde as intermediates), or by cytochrome P450-based oxidation of 1,1,2,2-tetrachloroethane 

(Halpert and Neal 1981; Yllner 1971). Dichloroacetic acid was identified as the major urinary metabolite 

in mice treated with 1,1,2,2-tetrachloroethane by intraperitoneal injection (Yllner 1971) and in in vitro 

systems with rat liver microsomal and nuclear cytochrome P450 (Casciola and Ivanetich 1984; Halpert 

1982; Halpert and Neal 1981). Dichloroacetic acid can be further metabolized to glyoxylic acid, formic 

acid, and carbon dioxide (Yllner 1971), with carbon dioxide a potential major component of the end 

products (Mitoma et al. 1985; Yllner 1971). Other pathways involve the formation of trichloroethylene or 

tetrachloroethylene as initial metabolites, with subsequent reactions yielding trichloroethanol, 

trichloroacetic acid, and oxalic acid as important end products (Ikeda and Ohtsuji 1972; Mitoma et al. 

1985; Yllner 1971). 
 

 

 

1,1,2,2-TETRACHLOROETHANE 73 

3. HEALTH EFFECTS 

Figure 3-3. Suggested Metabolic Pathways of 1,1,2,2-Tetrachloroethane 

Covalent binding and lipid peroxidation 

• 

CHCl2CHCl 

free radicals 

e d a
 

CCl2:CHCl
 CHCl2CHCl2 CHCl 2CHO 

trichloroethylene b dichloroacetaldehyde 

c 

CCl3CHO CCl2:CCl2 CHCl2COOH 

trichloroacetaldehyde tetrachloroethylene dichloroaceticacid 

CCl3CH2OH CCl3COOH HOOC•COOH CHO COOH CH2NH2COOH 

trichloroethanol trichloroacetic oxalic acid glyoxylic acid glycine 

acid 

CO2 + HCOOH CO2 

formic acid 

Key 

single metabolic step 

multiple metabolic steps 

a stagewise hydrolytic cleavage 

b P450-dependent oxidation 

c non-p450 oxidation 

d non-enzymatic dehydrochlorination 

e reductivedechlorination 
 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 74 

3. HEALTH EFFECTS 

Metabolism of 1,1,2,2-tetrachloroethane is generally extensive, with 68% or more of a total administered 

dose found as metabolites (Hanley et al. 1988; Mitoma et al. 1985; Yllner 1971). Mice that were given a 

single 0.16–0.32 g/kg intraperitoneal dose of 14C-labeled 1,1,2,2-tetrachloroethane eliminated 45–61% of 

the administered radioactivity as carbon dioxide in the expired air and 23–34% of the radioactivity in 

urine in the following 3 days (Yllner 1971). Dichloroacetic acid, trichloroacetic acid, trichloroethanol, 

oxalic acid, glyoxylic acid, and urea accounted for 27, 4, 10, 7, 0.9, and 2% (mean) of the urinary 

radioactivity excreted in 24 hours, respectively. In rats, trichloroethanol appeared to be present as a 

urinary metabolite at approximately 4-fold greater levels than trichloroacetic acid following a single 

8-hour inhalation exposure (Ikeda and Ohtsuji 1972). Several studies have reported that metabolism of 

1,1,2,2-tetrachloroethane is greater in mice than in rats; the magnitudes of the reported differences are 

generally in the range of a 1.1–3.5-fold greater metabolic activity, on a per-kg basis, in mice (Hanley et 

al. 1988; Milman et al. 1984; Mitoma et al. 1985). 

As indicated above, cytochrome P450-based metabolism of 1,1,2,2-tetrachloroethane to dichloroacetic 

acid has been demonstrated in vitro. Multiple P450 isozymes are likely to be involved, as demonstrated 

by studies reporting increased metabolism and covalent binding of metabolites following pretreatment 

with phenobarbital (Casciola and Ivanetich 1984; Halpert 1982), xylene (Halpert 1982), or ethanol (Sato 

et al. 1980); isozymes induced by these chemicals include members of the CYPIIA, CYPIIB, CYPIIE, 

and CYPIIIA subfamilies (Nebert et al. 1987; Omiecinski et al. 1999). Pretreatment with acetone did not 

appear to alter the toxicity of 1,1,2,2-tetrachloroethane, although cytochrome P450 levels were not 

evaluated (Charbonneau et al. 1991). 1,1,2,2-Tetrachloroethane also has been reported to cause 

inactivation of cytochrome P450. 1,1,2,2-Tetrachloroethane effectively inactivated the major 

phenobarbital-inducible P450 isozyme, but not the major P450 isozyme induced by β-naphthoflavone, in 

rat liver in vitro (Halpert et al. 1986). Rat liver nuclear cytochrome P450 activity was reduced following 

in vitro incubation with 1,1,2,2-tetrachloroethane and a NADPH-generating system (Casciola and 

Ivanetich 1984). In an in vivo study, cytochrome P450 activity was evaluated in male and female Swiss 

Albino mice 24 hours after a single 0, 300, or 600 mg/kg intraperitoneal dose of 1,1,2,2-tetrachloroethane 

(Paolini et al. 1992). 1,1,2,2-Tetrachloroethane treatment reduced total cytochrome P450 activity 

significantly in both sexes at both dose levels, suggesting that it may act as a suicide inhibitor of the 

enzyme. Treatment with 600 mg/kg reduced the microsomal activity of P450 isozymes IIIA, IIE1, IA2, 

IIB1, and IA1 in both sexes, and 300 mg/kg reduced the activity of P450IIIA in both sexes and P450IIB1 

in males. The only evidence of a significant role for glutathione was the observation of a 17% reduction 
 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 75 

3. HEALTH EFFECTS 

in glutathione S-transferase (GST) activity toward 1-chloro-2,4-dinitrobenzene (a general GST substrate) 

in mice of the 600 mg/kg dose group. 

Following an intravenous injection of radiolabeled 1,1,2,2-tetrachloroethane, parts of the radioactivity 

could not be extracted from liver, adrenal cortex, and testis, indicating the presence of covalently bound 

metabolites (Eriksson and Brittebo 1991) and implicating the formation of free radical intermediates 

during the metabolic process; the formation of free radicals from 1,1,2,2-tetrachloroethane metabolism 

has been demonstrated in spin-trapping experiments (Paolini et al. 1992; Tomasi et al. 1984). The 

observation of covalent binding to tissues is supported by the studies of Hanley et al. (1988), which 

reported significant levels of covalent binding in hepatic tissues after inhalation of radiolabeled 

1,1,2,2-tetrachloroethane; mice were found to have approximately a 1.9-fold greater extent of hepatic 

covalent binding than rats, which the study authors noted was consistent with the greater metabolism, on 

a per-kg basis, in mice compared to rats. Other findings suggested that at least a portion of the binding of 

radiolabel in liver DNA in mice exposed to a single 150 mg/kg oral dose of 14C-1,1,2,2-tetrachloroethane 

may have been from metabolic breakdown (Hanley et al. 1988). After a 4-week oral exposure of 

unlabeled 1,1,2,2-tetrachloroethane followed by a single oral dose of labeled 1,1,2,2-tetrachloroethane, 

Mitoma et al. (1985) also reported greater levels of tissue covalent binding in mice compared to rats; the 

differences were on the order of 2-fold greater binding in mice, which would be consistent both with the 

Hanley et al. (1988) studies and with the observed differences in metabolism of the two species discussed 

above. This may also be related to the 3.2–3.5-fold greater absorption, on a per-kg basis, following 

inhalation exposure to mice than to rats (Hanley et al. 1988). 

The kinetic constants of 1,1,2,2-tetrachloroethane metabolism in rats exposed to 350 ppm of the chemical 

for 6 hours were determined in gas uptake studies performed by Gargas and Andersen (1989). The rate of 

exhalation of 1,1,2,2-tetrachloroethane was measured and, combined with previously published values for 

partition coefficients for blood/air, liver/blood, muscle/blood, and fat/blood, allowed the successful 

estimation of the disposition of the chemical in rat (Gargas et al. 1989). A Km of 4.77 μM and a Vmax of 

12 mg/hour (scaled to a l-kg rat) were measured. 

3.4.4 Elimination and Excretion 

Available animal data indicate that following absorption into the body, 1,1,2,2-tetrachloroethane is 

eliminated mainly as metabolites in urine and carbon dioxide and unchanged compound in expired air 

(Gargas and Andersen 1989; Hanley et al. 1988; Ikeda and Ohtsuji 1972; Mitoma et al. 1985; Yllner 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 76 

3. HEALTH EFFECTS 

1971). The patterns of elimination in rats and mice are qualitatively similar (Hanley et al. 1988; Mitoma 

et al. 1985), although covalent binding is somewhat greater in mice than rats. Elimination is fairly rapid, 

with significant amounts present in the urine and expired air at 48–72 hours postexposure (Hanley et al. 

1988; Ikeda and Ohtsuji 1972; Mitoma et al. 1985; Yllner 1971). 

Covalent binding of metabolites of 1,1,2,2-tetrachloroethane may result in delays in elimination, as 

reflected in high levels of compound detected in the carcass of animals. Milman et al. (1984) reported in 

an abstract that 45% of the activity from a single radiolabeled oral dose of 1,1,2,2-tetrachloroethane was 

recovered in the carcass, although the evaluation time was not reported. A later study by the same authors 

(Mitoma et al. 1985) reported a 30.75% retention in the carcass of rats and a 27.44% retention in the 

carcass of mice 48 hours after exposure to a single labeled dose of 1,1,2,2-tetrachloroethane. Hanley et 

al. (1988) reported 30% retention in the carcass in rats exposed to 10 ppm by inhalation, 25% in mice 

exposed to 10 ppm by inhalation, 23% in rats exposed to 150 mg/kg by gavage, and 17.3% in mice 

exposed to 150 mg/kg by gavage. Colacci et al. (1987) reported covalent binding of radiolabeled 

1,1,2,2-tetrachloroethane to DNA, RNA, and protein in the liver, kidney, lung, and stomach of rats and 

mice exposed to a single intravenous dose and analyzed 22 hours postexposure. In vitro binding to calf 

thymus DNA was found to be greatest when the microsomal fraction was present, and was inhibited by 

SKF-525A, indicating that metabolic activation was likely required for DNA binding (Colacci et al. 

1987). 

3.4.4.1 Inhalation Exposure 

A study on volunteers showed that 3% of inhaled 1,1,2,2-tetrachloroethane was excreted in the breath, 

and that the urinary excretion rate was 0.015% of the absorbed dose/minute (Morgan et al. 1970). 

The excretion of 1,1,2,2-tetrachloroethane was tracked for 72 hours following exposure of rats and mice 

to vapor concentrations of 10 ppm 14C-1,1,2,2-tetrachloroethane for 6 hours (Hanley et al. 1988). More 

than 90% of the absorbed dose was metabolized in both species. The percentage of the recovered 

radioactivity was reported as follows: in rats, 33% in breath (25% as CO2 and 8% as unchanged 

compound), 19% in urine, and 5% in feces; in mice, 34% in breath (32% as CO2 and 2% as unchanged 

compound), 26% in urine, and 6% in feces. Radioactivity in urine and feces was nonvolatile (inferred by 

the researchers to be product(s) of metabolism), but was not otherwise characterized. 
 

 

 

 

1,1,2,2-TETRACHLOROETHANE 77 

3. HEALTH EFFECTS 

3.4.4.2 Oral Exposure 

No studies were located regarding excretion in humans following oral exposure to 1,1,2,2-tetrachloroethane. 

The excretion of 1,1,2,2-tetrachloroethane was followed for 72 hours following oral administration of 

150 mg/kg doses to rats and mice (Hanley et al. 1988). Greater than 90% of the absorbed dose was 

metabolized in both species. In rats, 41% was excreted in breath (32% as CO2 and 9% as unchanged 

compound), 23% in urine, and 4% in feces. In mice, 51% was excreted in breath, 22% in urine, and 6% 

in feces. Radioactivity in urine and feces was nonvolatile (inferred by the researchers to be product(s) of 

metabolism), but was not otherwise characterized. 

Mice given an oral dose of 1,1,2,2-tetrachloroethane excreted about 10% of the dose unchanged in the 

breath. The rest was metabolized and excreted in the breath as CO2 (10%), in the urine and feces (30%, 

measured together), and retained in the carcass (27%) after 48 hours. Rats showed similar patterns of 

excretion (Mitoma et al. 1985). 

3.4.4.3 Dermal Exposure 

No studies were located regarding excretion in humans following dermal exposure to 1,1,2,2-tetrachloroethane. 

A study describing the elimination of 1,1,2,2-tetrachloroethane in guinea pigs demonstrated that, 

following dermal absorption, about half of the 1,1,2,2-tetrachloroethane in the blood is eliminated in 

2 hours (Jakobson et al. 1982). 

3.4.4.4 Other Routes of Exposure 

The most comprehensive study of the metabolism and excretion of 1,1,2,2-tetrachloroethane was an 

intraperitoneal study in mice using 14C-labeled 1,1,2,2-tetrachloroethane. This study showed that after 

72 hours, about 4% of the radioactivity was expired unchanged in the breath, 50% was expired as CO2, 

28% was excreted in the urine, 1% was in the feces, and 16% remained in the carcass (Yllner 1971). 
 

 

 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 78 

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 and 

Krishnan 1994; Andersen et al. 1987). 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 parameterization, (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 

adequately described, however, this simplification is desirable because data are often unavailable for 
 

 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 79 

3. HEALTH EFFECTS 

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 3-4 shows a conceptualized representation of a PBPK model. 

If PBPK models for 1,1,2,2-tetrachloroethane 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. 

Gargas and Andersen (1989) described using a modified PBPK model for styrene (Ramsey and Anderson 

1984) and measurements of parent compound in exhaled breath of previously-exposed rats to estimate 

in vivo kinetic constants for 1,1,2,2-tetrachloroethane. However, no PBPK models specific to 

1,1,2,2-tetrachloroethane were located. 

3.5 MECHANISMS OF ACTION 

3.5.1 Pharmacokinetic Mechanisms 

Based upon its physical and chemical properties (a low molecular weight and highly lipophilic volatile 

organic compound), 1,1,2,2-tetrachloroethane is likely to be rapidly and extensively absorbed following 

both oral and inhalation exposures. This expectation is consistent with reported absorption of 70–100% 

in oral animal studies (Hanley et al. 1988; Mitoma et al. 1985) and 40–97% in human inhalation studies 

(Lehmann and Schmidt-Kehl 1936; Morgan et al. 1970), although the human data are uncertain due to 

unorthodox and dated study protocols that were used to assess uptake. Because 1,1,2,2-tetrachloroethane 

is a volatile, lipophilic molecule of small molecular size that appears to be readily absorbed from the 

respiratory and gastrointestinal tracts, passive diffusion is the most likely mechanism of absorption. 
 

 

1,1,2,2-TETRACHLOROETHANE 80 

3. HEALTH EFFECTS 

Figure 3-4. Conceptual Representation of a Physiologically Based
 

Pharmacokinetic (PBPK) Model for a 

Hypothetical Chemical Substance
 

Lungs 

Liver 

Fat 

Slowly 

perfused 

tissues 

Richly 

perfused 

tissues 

Kidney 

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 

Vmax 

Km 

Ingestion 

Inhaled chemical Exhaled chemical 

GI 

Tract 

Feces 

Urine

 Chemicals 

contacting skin 

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. 

Source: adapted from Krishnan and Andersen 1994 
 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 81 

3. HEALTH EFFECTS 

Following absorption, 1,1,2,2-tetrachloroethane is readily distributed throughout the body, although the 

high tissue:air partition coefficient for fat (Gargas et al. 1989) suggests that 1,1,2,2-tetrachloroethane may 

accumulate more in lipid-rich tissues. Distribution likely occurs predominantly via passive diffusion. 

Metabolism of 1,1,2,2-tetrachloroethane is extensive, with 68% or more of a total administered dose 

generally found as metabolites (Hanley et al. 1988; Mitoma et al. 1985; Yllner 1971). The metabolism of 

1,1,2,2-tetrachloroethane, as well as covalent binding of reactive metabolites to protein and DNA, is 

likely to be most prominent in the liver. 

Urinary elimination occurs mainly as metabolites, including glyoxalic acid, formic acid, trichloroethanol, 

and trichloroacetic acid, while a fraction of an absorbed dose may be eliminated in the expired air as 

parent compound or carbon dioxide (Gargas and Andersen 1989; Hanley et al. 1988; Ikeda and Ohtsuji 

1972; Mitoma et al. 1985; Yllner 1971). Passive diffusion is the most likely major mechanism of 

excretion. Covalent binding of metabolites of 1,1,2,2-tetrachloroethane (Colacci et al. 1987; Hanley et al. 

1988; Milman et al. 1984; Mitoma et al. 1985) may result in delays in elimination. 

3.5.2 Mechanisms of Toxicity 

Metabolism of 1,1,2,2-tetrachloroethane to reactive products is likely to play a key role in its toxicity. 

Both nuclear and microsomal cytochrome P450 enzymes have been implicated in the metabolism of the 

compound, possibly releasing a number of biologically active compounds, including aldehydes, alkenes, 

acids, and free radicals (see Figure 3-3 in Section 3.3) that may react with biological tissues. Evidence 

for metabolism to reactive compounds comes from studies of binding of radiolabeled 1,1,2,2-tetrachloroethane to tissues that was enhanced by pretreatment with phenobarbital, xylene, or ethanol; the variety of 

inducers capable of influencing this effect suggests that multiple P450 isozymes may be involved. 

Additionally, mice are known to metabolize 1,1,2,2-tetrachloroethane at a 1.1–3.5-fold greater rate than 

rats (Hanley et al. 1988; Milman et al. 1984; Mitoma et al. 1985) and have been demonstrated to have 

approximately 2-fold greater covalent binding to tissues (Mitoma et al. 1985), further implicating 

metabolic activation as a possible mode of action. Thus, for tissues high in metabolic capacity, such as 

the liver, the formation of active metabolites is a likely mechanism for the toxicity of 1,1,2,2-tetrachloroethane. 

The presence of the functional group consisting of a terminal dichloromethyl moiety in a molecule, as 

typified by the drug chloramphenicol, is known to confer toxicity. Chloramphenicol and other 

dichloromethyl compounds are hydroxylated to form, after spontaneous dehydrohalogenation, reactive 
 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 82 

3. HEALTH EFFECTS 

acyl chloride intermediates (Halpert 1981; Halpert et al. 1986), which subsequently bind to crucial 

proteins to exert their effects. Alternately, these acid chlorides can hydrolyze to form their respective 

acids. There was clear evidence in the literature reviewed that these pathways were operant for 

1,1,2,2-tetrachloroethane. Cytochrome P-450 was found to catalyze the formation of both 

dichloroacetylated protein adducts (Halpert 1982) and dichloroacetic acid (Halpert 1981). These 

biotransformation reactions were increased by chronic ethanol consumption and fasting, preconditions 

that are known to induce the levels of cytochrome P-450 isoenzyme IIE1 (Johansson et al. 1988; Soucek 

and Gut 1992). Significantly, a number of low molecular weight volatile halocarbons are metabolized by 

this isoform, suggesting that it may be the major contributor to the metabolism of 1,1,2,2-tetrachloroethane as well (Guengerich et al. 1991). 

As part of an investigation into the reductive metabolism of 1,1,2,2-tetrachloroethane in mice, Paolini and 

coworkers trapped a carbon-centered radical formed in vivo by reductive dehalogenation of 1,1,2,2-tetrachloroethane, a reaction presumably mediated by cytochrome P-450 (Paolini et al. 1992). Tomasi et al. 

(1984) demonstrated the formation of free radicals from 1,1,2,2-tetrachloroethane metabolism as well. 

Paolini et al. (1992) also identified conjugated diene hydroperoxides formed in endoplasmic reticulum of 

mice that had been exposed to 600 mg/kg 1,1,2,2-tetrachloroethane. Collectively, these findings are 

indicative of a mechanism of action whereby 1,1,2,2-tetrachloroethane metabolism could result in the 

reductive formation of radical products, leading to the stimulation of lipid peroxidation and its attendant 

hepatotoxic effects, a scenario that has been demonstrated for the structurally-related chlorinated 

alkane,carbon tetrachloride. Additionally, both dichloro- and trichloroacetic acids are known to cause 

proliferation of peroxisomes (DeAngelo et al. 1986). In the work presented by Hanley et al. (1988), this 

property of the acid metabolites of 1,1,2,2-tetrachloroethane was noted, and suggested as a possible 

mechanism by which the halocarbon could elicit hepatotoxic responses. 

The mechanism behind the neurological effects of high-dose exposures to 1,1,2,2-tetrachloroethane has 

not been well characterized. While it is possible that metabolic activation may play a role in causing 

these effects, studies of similar compounds suggest that the parent compound may be the causative agent. 

In general, the highly lipophilic nature of chlorinated hydrocarbons, such as 1,1,2,2-tetrachloroethane, 

allows them to cross the blood-brain barrier readily and partition into lipids in neuronal membranes. This 

property allows them to interfere with neural membrane function, bringing about central nervous system 

depression, behavioral changes, and anesthesia (Klaassen 1996). Recent studies indicate that most 

compounds used as general anesthetics are capable of modulating neurotransmitter-gated ion channels, 

particularly receptors for GABA and glutamate, at clinical concentrations (Hemmings et al. 2005). It is 
 

 

 

 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 83 

3. HEALTH EFFECTS 

feasible that 1,1,2,2-tetrachloroethane could act in a similar manner, although studies describing the 

mechanism of 1,1,2,2-tetrachloroethane-induced neurological effects are not available. 

The mode of action of the carcinogenic effects of 1,1,2,2-tetrachloroethane is incompletely characterized. 

Genotoxicity studies provide only limited evidence of a genotoxic mode of action. 1,1,2,2-Tetrachloroethane has weak genotoxic activity, with in vitro genotoxicity tests generally reporting negative results 

except for assays of SCE and cell transformation; in vivo tests of genotoxicity have shown a similar 

pattern. 1,1,2,2-Tetrachloroethane has been shown to bind to DNA in the liver and several other organs 

organs in rats and mice in vivo (Colacci et al. 1987; Hanley et al. 1988), indicating that this mechanism 

may contribute to the carcinogenic process. Several studies of 1,1,2,2-tetrachloroethane toxicity have 

reported increases in the number of hepatocytes in mitosis, but the possible role these effects may have on 

the carcinogenicity of 1,1,2,2-tetrachloroethane has not been evaluated. The results of rat liver 

preneoplastic foci and mouse BALB/c-3T3 cell neoplastic transformation assays suggest that 

1,1,2,2-tetrachloroethane may have initiating and promoting activity (Colacci et al. 1992, 1996; Milman 

et al. 1988; Story et al. 1986), but tumor initiation and promotion studies have not been conducted to 

elucidate these potential modes of action. 

It is likely that tumor formation by 1,1,2,2-tetrachloroethane involves metabolism to one or more active 

compounds, that in turn result in carcinogenicity. 1,1,2,2-Tetrachloroethane is metabolized extensively 

following absorption, presumably at least in part by cytochrome P450 enzymes. Urinary metabolites of 

1,1,2,2-tetrachloroethane include dichloroacetic acid, trichloroacetic acid, trichloroethylene, and 

tetrachloroethylene (Section 3.4.3). Chronic exposure of rats and mice to trichloroacetic acid, 

trichloroethylene, and tetrachloroethlyene had similar effects as were reported in the NCI (1978) 

carcinogenicity study of 1,1,2,2-tetrachloroethane, with hepatic tumors in male and female mice but not in 

rats of either sex (Bull et al. 1990; Herren-Freund et al. 1987; NCI 1976, 1977; NTP 1986, 1990; Pereira 

1996; Pereira and Phelps 1996). Dichloroacetic acid has also been demonstrated to cause hepatocellular 

tumors in both male and female mice (Bull et al. 1990; Daniel et al. 1992; DeAngelo et al. 1991, 1999; 

Pereira 1996; Pereira and Phelps 1996); dichloroacetic acid has been shown to cause liver tumors in rats 

as well, but the results are not as striking as in mice (DeAngelo et al. 1996; Richmond et al. 1995). 

Dichloroacetic acid, trichloroacetic acid, trichloroethylene, and tetrachloroethylene have similar 

genotoxicity profiles as 1,1,2,2-tetrachloroethane, adding further support to the possibility that 

metabolism to one or more of these compounds may be involved in the carcinogenicity of 1,1,2,2-tetrachloroethane. Mice are known to metabolize 1,1,2,2-tetrachloroethane to a greater extent than rats, which 

may in part account for the fact that liver tumors occurred in mice, but not in rats, following chronic oral 
 

 

 

 

 

 

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exposure. Although it is plausible that the carcinogenicity of 1,1,2,2-tetrachloroethane involves 

metabolism to one or more active compounds, there is no direct evidence linking one or more metabolites 

to its carcinogenic effects. 

In addition to being metabolized to carcinogenic compounds, 1,1,2,2-tetrachloroethane may be 

metabolized to form free radicals, which can, in turn, covalently bind to tissues, including DNA. 

Formation of free radicals during 1,1,2,2-tetrachloroethane metabolism has been demonstrated in spintrapping experiments (Paolini et al. 1992; Tomasi et al. 1984). Both nuclear and microsomal forms of 

cytochrome P450 enzymes have been implicated in this process, as increased metabolism and covalent 

binding of metabolites following pretreatment with phenobarbital (Casciola and Ivanetich 1984; Halpert 

1982), xylene (Halpert 1982), or ethanol (Sato et al. 1980) have been reported. The presence of 

covalently bound label has been reported following inhalation (Hanley et al. 1988), oral (Mitoma et al. 

1985), and intravenous (Eriksson and Brittebo 1991) administration of radiolabeled 1,1,2,2-tetrachloroethane. 

3.5.3 Animal-to-Human Extrapolations 

Limited information is available regarding the pharmacokinetic properties of 1,1,2,2-tetrachloroethane in 

humans. Species-specific differences in pharmacokinetic properties of 1,1,2,2-tetrachloroethane have 

been demonstrated in rats and mice. Results of Hanley et al. (1988) indicate a 3.2–3.5-fold greater 

absorption of 1,1,2,2-tetrachloroethane (on a per-kg basis) in mice than rats following inhalation 

exposure. Several studies have reported that metabolism of 1,1,2,2-tetrachloroethane is greater in mice 

than in rats; the magnitudes of the reported differences are generally in the range of a 1.1–3.5-fold greater 

metabolic activity in mice (Hanley et al. 1988; Milman et al. 1984; Mitoma et al. 1985). After a 4-week 

oral exposure of unlabeled 1,1,2,2-tetrachloroethane followed by a single oral dose of labeled 

1,1,2,2-tetrachloroethane, Mitoma et al. (1985) also reported greater levels of tissue covalent binding in 

mice compared to rats; the differences were on the order of 2-fold greater binding in mice. 

Based on pharmacokinetic differences between rats and mice and limited human pharmacokinetic data for 

1,1,2,2-tetrachloroethane, animal-to-human extrapolations include considerable uncertainty. Because 

metabolism of 1,1,2,2-tetrachloroethane is greater in mice than rats, it is reasonable to expect that mice 

might be more susceptible than rats to 1,1,2,2-tetrachloroethane toxicity. In general, the order of 

metabolic rates for other chlorinated solvents is mice>rats>humans. 
 

 

 

 

 

 

 

 

 

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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 Thomas and Colborn (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, 

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). 

No human data were located regarding the potential for 1,1,2,2-tetrachloroethane to affect the endocrine 

system. Based on available animal data, the endocrine system does not appear to be a target of 

1,1,2,2-tetrachloroethane toxicity (Gohlke and Schmidt 1972; Horiuchi et al. 1962; NCI 1978; NIOSH 

1978; NTP 2004a). However, it should be noted that test data for classical and emerging neuroendocrine 

endpoints (e.g., hormone levels, receptor binding/mediated assays, etc.) are not presently available for 
 

 

 

 

 

 

 

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1,1,2,2-tetrachloroethane. Furthermore, available animal data are limited due to relatively crude 

assessment of reproductive and endocrinological endpoints (i.e., histopathology of reproductive and 

endocrine tissues and effects on sperm parameters). 

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 
 

 

 

 

 

 

 

 

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Kearns 1997; NRC 1993; Vieira et al. 1996). Whether differences in xenobiotic metabolism make the 

child more or less susceptible also depends on whether the relevant enzymes are involved in activation of 

the parent compound to its toxic form or in detoxification. There may also be differences in excretion, 

particularly in newborns who all have a low glomerular filtration rate and have not developed efficient 

tubular secretion and resorption capacities (Altman and Dittmer 1974; NRC 1993; West et al. 1948). 

Children and adults may differ in their capacity to repair damage from chemical insults. Children also 

have a longer remaining lifetime in which to express damage from chemicals; this potential is particularly 

relevant to cancer. 

Certain characteristics of the developing human may increase exposure or susceptibility, whereas others 

may decrease susceptibility to the same chemical. For example, although infants breathe more air per 

kilogram of body weight than adults breathe, this difference might be somewhat counterbalanced by their 

alveoli being less developed, which results in a disproportionately smaller surface area for alveolar 

absorption (NRC 1993). 

Studies in humans and animals have not examined the effect of 1,1,2,2-tetrachloroethane exposure on the 

immature organism. The limited data evaluating the effect of 1,1,2,2-tetrachloroethane on developing rats 

and mice have not indicated effects on the offspring at levels that did not also cause maternal effects 

(NTP 1991a, 1991b; Schmidt et al. 1972). Because metabolism of 1,1,2,2-tetrachloroethane to reactive 

products is likely to play a key role in 1,1,2,2-tetrachloroethane toxicity, potential age-related differences 

in metabolism could result in age-related differences in susceptibility to the toxic effects of exposure to 

1,1,2,2-tetrachloroethane. For example, the well-recognized metabolic immaturity of hepatic enzymes 

during infancy (Ginsberg et al. 2002, 2004) might be protective against 1,1,2,2-tetrachloroethane-induced 

liver effects since these effects appear to require hepatic metabolism. How this would ultimately affect 

risk is difficult to predict since the ability to remove toxic metabolites may also be immature. 

The mechanism behind the neurological effects of high-dose exposures to 1,1,2,2-tetrachloroethane is not 

well characterized, but studies of similar compounds suggest that the parent compound may be the causal 

agent (Section 3.5.2). The amount of parent 1,1,2,2-tetrachloroethane that has the opportunity to reach 

the central nervous system and produce neurotoxicity may be greater in infants than adults. Reasons for 

this include immaturity in hepatic metabolism (which could lead to longer-half life of parent compound, 

higher blood levels and thus greater amounts reaching the central nervous system), and immaturity of the 

blood-brain barrier (which could result in increased distribution into the central nervous system). 
 

 

 

 

 

 

 

 

 

 

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Children may be more vulnerable to 1,1,2,2-tetrachloroethane since intake dose per kilogram of body 

weight may be greater in early life than in mature humans, because children eat more food, drink more 

water, breathe more air, and ingest more soil/house dust per kilogram body weight than older age groups 

(EPA 2002; NRC 1993). There are no reports on levels of 1,1,2,2-tetrachloroethane in breast milk 

(Section 6.6). PBPK models for similar chlorinated solvents (e.g., Fisher et al. 1997) suggest that 

1,1,2,2-tetrachloroethane may not present a particularly large breast milk concern for nursing infants, 

largely because of its rapid metabolism by the maternal system. 

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, 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 1,1,2,2-tetrachloroethane 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 
 

 

 

 

 

 

 

 

 

 

 

 

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3. HEALTH EFFECTS 

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 1,1,2,2-tetrachloroethane are discussed in Section 3.8.2. 

A biomarker of susceptibility is an indicator of an inherent or acquired limitation of an organism's ability 

to respond to the challenge of exposure to a specific xenobiotic substance. It can be an intrinsic genetic or 

other characteristic or a preexisting disease that results in an increase in absorbed dose, a decrease in the 

biologically effective dose, or a target tissue response. If biomarkers of susceptibility exist, they are 

discussed in Section 3.10, Populations That Are Unusually Susceptible. 

3.8.1 Biomarkers Used to Identify or Quantify Exposure to 1,1,2,2-Tetrachloroethane 

There currently are no specific biomarkers available to quantify exposure to 1,1,2,2-tetrachloroethane. 

Metabolites of 1,1,2,2-tetrachloroethane, including trichloroacetic acid, trichloroethanol, and 

trichloroethanol glucuronide, may be measured in blood and urine (Breimer et al. 1974; Christensen et al. 

1988; Koppen et al. 1988) (see Chapter 7). However, these metabolites are produced by other common 

chlorinated alkanes and would not be specifically indicative of exposure to 1,1,2,2-tetrachloroethane. 

Also, available animal data indicate that 1,1,2,2-tetrachloroethane is rapidly metabolized and excreted, 

primarily within the first 3 days postexposure (Yllner 1971). Therefore, tests for the presence of 

1,1,2,2-tetrachloroethane or its metabolites would only be useful if performed shortly following exposure. 

3.8.2 Biomarkers Used to Characterize Effects Caused by 1,1,2,2-Tetrachloroethane 

There currently are no biomarkers available to characterize effects caused by 1,1,2,2-tetrachloroethane. 

However, since 1,1,2,2-tetrachloroethane has the potential to cause liver damage at high doses, it may be 

possible to correlate changes in urinary metabolites with serum indicators of liver malfunction, although 

the metabolites would not be specific for 1,1,2,2-tetrachloroethane. 1,1,2,2-Tetrachloroethane has been 

shown to bind to DNA in the liver (and to a lesser extent the kidney, lung, and stomach) of rats and mice 

in vivo (Colacci et al. 1987; Hanley et al. 1988), suggesting that it may be plausible to use DNA adducts 

in peripheral blood lymphocytes as a biomarker of effects (as has been done for numerous genotoxic 

agents). 
 

 

 

 

 

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3.9 INTERACTIONS WITH OTHER CHEMICALS 

In efforts to find treatments for acute-duration 1,1,2,2-tetrachloroethane poisoning, various substances 

have been tested to determine if they altered the toxicity of 1,1,2,2-tetrachloroethane in rats 

(Laass 1973a, 1973b, 1974a, 1974b). The survival times were increased when 1,1,2,2-tetrachloroethane 

was administered with castor oil, but decreased when administered orally with milk. Survival time was 

also decreased when 1,1,2,2-tetrachloroethane was given with mineral oil or with paraffin. 

Alcohol, an inducer of cytochrome P-450 form IIE1, increased the metabolism of 1,1,2,2-tetrachloroethane (Sato et al. 1980) and intensified the effects of 1,1,2,2-tetrachloroethane in rats (Gohlke and 

Schmidt 1972). This indicates that humans who consume alcohol may be at increased risk for toxic 

effects from 1,1,2,2-tetrachloroethane. This is also the case for several other chlorinated aliphatic 

hydrocarbons. However, although alcohol combined with 1,1,2,2-tetrachloroethane increased the relative 

weight of the testes in rats (Schmidt et al. 1972), it did not alter the effects of 1,1,2,2-tetrachloroethane on 

the histopathology or function in the liver, nor was there damage to the kidneys, spleen, adrenals, brain, or 

thyroid. 

The potentiation of haloalkane-induced liver injury by acetone is a well-known phenomenon, as readily 

demonstrated in acetone-pretreated rats exposed to trichloroethylene-carbon tetrachloride mixture. 

Charbonneau et al. (1991) assessed the influence of acetone pretreatment on the severity of liver injury in 

rats administered various other haloalkane mixtures intraperitoneally. Acetone pretreatment did not 

increase the severity of liver injury induced by binary mixtures that included 1,1,2,2-tetrachloroethane. 

Whereas apparent additive hepatotoxicity was elicited by some of the tested binary mixtures that did not 

include 1,1,2,2-tetrachloroethane, binary mixtures of 1,1,2,2-tetrachloroethane and either 1,1-dichloroethylene or tetrachloroethylene appeared to be less hepatotoxic than 1,1-dichloroethylene or tetrachloroethylene alone, possibly due to competitive inhibition of metabolism. 

3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE 

A susceptible population will exhibit a different or enhanced response to 1,1,2,2-tetrachloroethane than 

will most persons exposed to the same level of 1,1,2,2-tetrachloroethane 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 1,1,2,2-tetrachloroethane, or compromised function of organs affected by 1,1,2,2-tetrachloroethane. Populations who 
 

 

 

 

 

 

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are at greater risk due to their unusually high exposure to 1,1,2,2-tetrachloroethane are discussed in 

Section 6.7, Populations with Potentially High Exposures. 

As metabolism is believed to play an important role in the toxicity of 1,1,2,2-tetrachloroethane, 

particularly in the liver, individuals with elevated levels of cytochrome P450 enzymes may have an 

increased susceptibility to the compound. Halpert (1982) reported an increase in in vitro metabolite 

formation and in covalently bound metabolites following pretreatment with xylene or phenobarbital, both 

of which increased cytochrome P450 activity. Sato et al. (1980) similarly reported an increased 

metabolism of 1,1,2,2-tetrachloroethane in rats following ethanol pretreatment. Since 1,1,2,2-tetrachloroethane has been demonstrated to inhibit cytochrome P450 enzymes (Halpert 1982; Paolini et al. 1992), 

presumably through a suicide inhibition mechanism, it is also possible that people coexposed to chemicals 

that are inactivated by cytochrome P450 enzymes will be more susceptible to those compounds. Because 

the liver and nervous system are the main targets of 1,1,2,2-tetrachloroethane toxicity, individuals with 

compromised function of liver or nervous system may be at increased risk from exposure to 1,1,2,2-tetrachloroethane. 

Studies directly evaluating sex-related differences in toxicity following exposure to 1,1,2,2-tetrachloroethane are not available. Toxicity studies that evaluated both sexes in the same study did not show 

consistent sex-related differences. 

3.11 METHODS FOR REDUCING TOXIC EFFECTS 

This section will describe clinical practice and research concerning methods for reducing toxic effects of 

exposure to 1,1,2,2-tetrachloroethane. 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 

1,1,2,2-tetrachloroethane. When specific exposures have occurred, poison control centers and medical 

toxicologists should be consulted for medical advice. The following texts provide specific information 

about treatment following exposures to 1,1,2,2-tetrachloroethane: 

Ellenhorn MJ, Schonwald S, Ordog G, et al. 1997. 1,1,2,2-Tetrachloroethane. Ellenhorn’s medical 

toxicology: Diagnosis and treatment of human poisoning. 2nd ed. Baltimore, MD: Williams and 

Wilkins, 1436-1440. 

Goldfrank LR, Flomenbaum NE, Lewin NA, et al. 2002. Hydrocarbons. In: Goldfrank's toxicologic 

emergencies. New York, NY: McGraw Hill, 1303-1322. 
 

 

 

 

 

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Haddad LM, Shannon MW, Winchester JF. 1998. Clinical management of poisoning and drug overdose. 

3rd edition. Philadelphia, PA: W.B Saunders Company, 931-939. 

Parraga M, West JM. 1998. Hydrocarbons. In: Viccellio P, ed. Emergency toxicology. 2nd edition. 

Philadelphia, PA: Lippincott-Raven Publishers, 299-313. 

3.11.1 Reducing Peak Absorption Following Exposure 

Human exposure to 1,1,2,2-tetrachloroethane may occur by inhalation, ingestion, or dermal contact. 

Concentrated vapors are irritating to the eyes and upper respiratory tract, and once absorbed can cause 

central nervous system and respiratory depression. Unprotected skin exposure can cause defatting and 

subsequent dermatitis. Suggested treatment for exposed individuals includes moving them to fresh air 

and administering 100% humidified supplemental oxygen. The potential risk of rapid central nervous 

system and respiratory depression usually outweighs the potential risk (e.g., aspiration of vomitus) of 

administering syrup of ipecac to induce emesis (TOMES 1993). Once in the care of a health professional, 

gastric lavage is suggested if it can be performed within minutes of the exposure to reduce the amount of 

absorbed solvent. 

Following acute high-level exposure to some chlorinated solvents by any route, hypotension and cardiac 

arrhythmias due to myocardial sensitization to catecholamines have led to ventricular fibrillation and 

death (TOMES 1993). There is no specific treatment for 1,1,2,2-tetrachloroethane exposure except for 

supportive measures to combat the effects of central nervous system and respiratory depression, and 

cardiac arrhythmias. 

3.11.2 Reducing Body Burden 

The body does not retain significant amounts of 1,1,2,2-tetrachloroethane. Currently, there is no 

recognized treatment to enhance elimination. The orthodox treatment for ingestion is entirely supportive. 

One potential method for enhancing elimination is to increase the ventilation rate, thereby enhancing 

elimination via the lung. In a 6-year-old boy who had ingested 12–16 g of tetrachloroethylene, controlled 

hyperventilation over a 5-day period enhanced pulmonary excretion of the chemical (Koppel et al. 1985). 

This technique may be applicable to other volatile solvents like 1,1,2,2-tetrachloroethane, although its 

effectiveness for clearing 1,1,2,2-tetrachloroethane from the body is likely to be lower than for tetrachloroethylene, because tetrachloroethylene is particularly slowly metabolized (providing a better 

opportunity for clearance via exhalation) and has a much lower human blood-air partition coefficient 
 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 93 

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(10.3–19.8 [Agency for Toxic Substances and Disease Registry 1997] compared to 72.6– 

116 [Section 3.4.2]). 

Stimulation of the metabolism of 1,1,2,2-tetrachloroethane may also lead to enhanced elimination, but it 

can also result in formation of larger amounts of toxic metabolites. Thus, the risks of this approach may 

outweigh the benefits. 

3.11.3 Interfering with the Mechanism of Action for Toxic Effects 

Clinical effects caused by acute 1,1,2,2-tetrachloroethane exposure include central nervous system 

depression, nephritis, and toxic hepatitis (HSDB 2006). Other effects include malaise, dizziness, fatigue, 

headache, and lightheadedness, all of which may disappear rapidly after the exposure ceases. The 

mechanism of action for the central nervous system effects has not been clearly established, but it is 

probable that it is related to solvent effects on neuronal membranes exerted by many halogenated 

aliphatic hydrocarbons. 

Ethanol in alcoholic beverages may compete with or enhance the metabolic activation of solvents and 

could possibly increase the severity of health effects, particularly liver toxicity. Alcoholic beverages 

should be avoided by persons exposed to 1,1,2,2-tetrachloroethane and other solvents of this nature. 

Mechanisms have been proposed for the hepatotoxic action of this halocarbon (Halpert 1981; Halpert et 

al. 1986; Hanley et al. 1988). These include generation of reactive free radicals and acid chlorides. 

Dietary antioxidants may modulate the toxicity caused by the former, but no established treatments are 

available for the latter. It is concluded that avoiding co-exposures to substances that enhance the 

activation of 1,1,2,2-tetrachloroethane (e.g., acetone and ethanol) provide the best means of interfering 

with the toxification of the absorbed chemical. 

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 1,1,2,2-tetrachloroethane is available. Where adequate 

information is not available, ATSDR, in conjunction with the National Toxicology Program (NTP), is 
 

 

 

 

 

 

 

 

 

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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 1,1,2,2-tetrachloroethane. 

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 1,1,2,2-Tetrachloroethane 

The existing data on health effects of inhalation, oral, and dermal exposure of humans and animals to 

1,1,2,2-tetrachloroethane are summarized in Figure 3-5. The purpose of this figure is to illustrate the 

existing information concerning the health effects of 1,1,2,2-tetrachloroethane. 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. 

As seen in Figures 3-5, data exist for inhalation exposure of humans for death, systemic effects of acute-, 

intermediate-, and chronic-duration exposure, neurological effects, and cancer. A few human deaths have 

been reported following excessive inhalation exposure to 1,1,2,2-tetrachloroethane in occupational 

settings. Effects reported in humans exposed in the workplace consist of gastric distress including pain, 

nausea, vomiting, loss of appetite, and loss of body weight; increases in the number of white blood cells; 

jaundice, enlarged liver, liver degeneration, and cirrhosis; neurological symptoms such as headache, 

tremors, dizziness, numbness, and drowsiness; and possibly genital cancer and leukemia or lymphoma. 

In one experimental inhalation study, male volunteers experienced mucosal irritation, nausea, vomiting, 

and dizziness upon exposure to high levels of 1,1,2,2-tetrachloroethane. Data for oral exposure of 

humans consist mainly of case reports of suicidal or accidental ingestion of 1,1,2,2-tetrachloroethane, 

with data for death, systemic effects of acute-duration exposure, immunological/lymphoreticular, and 

neurological effects. Autopsy findings in suicide cases included congestion and edema in the lungs and 
 

1,1,2,2-TETRACHLOROETHANE 95 

3. HEALTH EFFECTS 

Figure 3-5. Existing Information on Health Effects of 1,1,2,2-Tetrachloroethane 

Death

Acute 

Intermediate 

Chronic 

Immunologic/Lymphoretic 

Neurologic 

Reproductive 

Developmental 

Genotoxic 

Cancer 

Systemic 

Inhalation 

Oral 

Dermal 

Human 

Death

Acute 

Intermediate 

Chronic 

Immunologic/Lymphoretic 

Neurologic 

Reproductive 

Developmental 

Genotoxic 

Cancer 

Systemic 

Inhalation 

Oral 

Dermal 

Animal 

Existing Studies 
 

 

 

 

1,1,2,2-TETRACHLOROETHANE 96 

3. HEALTH EFFECTS 

lung collapse, mucosal congestion of the esophagus and upper stomach, and epicardial and endocardial 

anoxic hemorrhage. In cases of humans accidentally given oral doses of 1,1,2,2-tetrachloroethane for 

parasite treatment, effects consisted of shallow breathing, pronounced lowering of blood pressure, and 

faint pulse during ensuing unconsciousness. One death was reported when a man cleaned up a 

1,1,2,2-tetrachloroethane spill with his bare hands. Workers in India's bangle industry who dipped their 

hands in 1,1,2,2-tetrachloroethane, as well as inhaled it, had tremors, headache, and dizziness in addition 

to gastric disturbances. Mucosal irritation of the eyes has also been observed in humans exposed to 

1,1,2,2-tetrachloroethane in air by direct contact of the concentrated vapor with the eyes. 

For animals exposed by inhalation, data exist for death; systemic effects of acute- and intermediateduration; and immunological/lymphoreticular, neurological, reproductive, and developmental effects. 

Systemic effects consisted of labored respiration, hematological effects, and hepatic effects. 

Immunological effects consisted of a decrease in titer and an increase in the electrophoretic mobility of 

specific antibodies to typhoid in rabbits and are considered of questionable toxicological significance. 

Neurological effects included decreased motor activity, loss of reflexes, ataxia, prostration, and narcosis. 

Limited information is available regarding reproductive or developmental endpoints in animals following 

inhalation of 1,1,2,2-tetrachloroethane. Data for oral exposure of animals exist for death; systemic effects 

of acute-, intermediate-, and chronic-duration exposure; immunological/lymphoreticular, neurological, 

and reproductive effects; and cancer. Systemic effects consisted of hepatic, thyroid, and adrenal effects, 

and decreases in body weight gain. Information on immunological/lymphoreticular effects is limited to 

histopathological effects on the spleen. Neurological effects consisted of central nervous system 

depression, debilitation, and decreased avoidance learning. An oral study in rats indicated an effect on 

spermatogenesis; however, the interpretation of the study was confounded by the fact that the rats had 

been maintained at a high temperature (35 °C). Cancer data consist of a significantly increased incidence 

of hepatocellular carcinoma in mice exposed orally. Existing data in animals exposed dermally to 

1,1,2,2-tetrachloroethane are limited to an LD50 in rabbits; karyopyknosis and pseudoeosinophilic 

infiltration in guinea pigs; and eye closure, squinting, and lacrimation in guinea pigs and rats acutely 

exposed to the vapors. 

3.12.2 Identification of Data Needs 

Acute-Duration Exposure. Numerous studies are available regarding the effects of acute-duration 

exposures to 1,1,2,2-tetrachloroethane, both in humans (Coyer 1944; Hepple 1927; Lehmann and 

Schmidt-Kehl 1936; Lilliman 1949; Mant 1953; Sherman 1953; Ward 1955) and animals (Cottalasso et 
 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 97 

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al. 1998; Deguchi 1972; Hanley et al. 1988; Horiuchi et al. 1962; Horvath and Frantik 1973; NTP 1991a, 

1991b, 1993a, 1993b, 2004a; Pantelitsch 1933; NIOSH 1978; Schmidt et al. 1980a; Tomokuni 1969, 

1970; Wolff 1978). These studies have identified the liver and central nervous system as the major organ 

systems affected in both humans and animals following inhalation and oral exposure. 

Information on the toxicity of acute inhalation exposure to 1,1,2,2-tetrachloroethane in humans comes 

from a poorly reported experimental study in which two volunteers self-inhaled various concentrations of 

the chemical for up to 30 minutes (Lehmann and Schmidt-Kehl 1936). The results of this study suggest 

that 3 ppm was the odor detection threshold, 13 ppm was tolerated without effect for 10 minutes, and 

146 ppm for 30 minutes or 336 ppm for 10 minutes caused irritation of the mucous membranes, pressure 

in the head, vertigo, and fatigue. Other early reports similarly indicate that common symptoms of highdose acute inhalation exposure to 1,1,2,2-tetrachloroethane include drowsiness, nausea, headache, and 

weakness, and at extremely high concentrations, jaundice, unconsciousness, and respiratory failure 

(Coyer 1944; Hamilton 1917). 

The preponderance of information on the acute inhalation toxicity of 1,1,2,2-tetrachloroethane in animals 

pertains to neurological and hepatic effects of near-lethal to lethal exposures (Carpenter et al. 1949; 

Horiuchi et al. 1962; Pantelitsch 1933; NIOSH 1978; Schmidt et al. 1980b). Death was typically 

preceded by signs of central nervous system toxicity (e.g., incoordination, loss of reflexes, labored 

respiration, prostration, and loss of consciousness), and postmortem examinations mainly showed 

congestion and fatty degeneration of the liver. Hepatotoxicity (Gohlke and Schmidt 1972; Schmidt et al. 

1972, 1980a; Tomokuni 1969, 1970) and neurotoxicity (Horvath and Frantik 1973; NIOSH 1978) have 

been reported in animals acutely exposed to nonlethal concentrations of 1,1,2,2-tetrachloroethane vapors. 

Information on the acute oral toxicity of 1,1,2,2-tetrachloroethane in humans is available from several 

case reports. In reports of intentional ingestion of lethal amounts of 1,1,2,2-tetrachloroethane (Elliott 

1933; Forbes 1943; Hepple 1927; Lilliman 1949; Mant 1953; Sherman 1953), subjects usually lost 

consciousness within approximately 1 hour and died 3–20 hours postingestion, depending on the amount 

of food in the stomach. Postmortem examinations showed gross congestion in the esophagus, stomach, 

kidneys, spleen, and trachea, gross congestion and edema in the lungs, and histological effects of 

congestion and cloudy swelling in the lungs, liver, and/or kidneys (Hepple 1927; Mant 1953). 

The preponderance of information on the acute-duration oral toxicity of 1,1,2,2-tetrachloroethane in 

animals is provided by gavage studies of rats and mice in which lethality was one of the end points 
 

 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 98 

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evaluated. LD50 values in rats range from 250 to 800 mg/kg (Gohlke et al. 1977; NTP 2004a; Schmidt et 

al. 1980a; Smyth et al. 1969). Lethality data are available for repeated gavage exposure in rats (NTP 

1993a, 1996) and mice (NTP 1993d). Dietary exposure for acute and intermediate exposure durations 

caused moribundity or death in rats (NTP 2004a) and mice (NTP 1991b, 2004a). Information is available 

on acute neurological, body weight, and liver effects in animals following acute-duration oral exposure to 

1,1,2,2-tetrachloroethane (Cottalasso et al. 1998; Hanley et al. 1988; NTP 1993a, 1993b, 2004a; Schmidt 

et al. 1980a; Wolff 1978), but most adverse changes were observed at near-lethal to lethal dose levels. 

In summary, derivation of acute-duration inhalation and oral MRLs for 1,1,2,2-tetrachloroethane are 

precluded by the lack of information regarding threshold response levels for less serious effects. 

Well designed studies that assess less serious threshold effects following acute-duration inhalation and 

oral exposure to 1,1,2,2-tetrachloroethane would facilitate the development of acute-duration MRL values 

for 1,1,2,2-tetrachloroethane. Data for dermal exposure routes are limited, but this is not a primary route 

of human exposure for persons living near hazardous waste sites where 1,1,2,2-tetrachloroethane may be 

found. 

Intermediate-Duration Exposure. Reports of intermediate-duration exposures to humans by the 

inhalation and oral routes have been somewhat anecdotal and dated, and their interpretations complicated 

by uncertainties in levels of exposure to 1,1,2,2-tetrachloroethane and other chemicals (Jeney et al. 1957; 

Koelsch 1915; Lobo-Mendonca 1963; Minot and Smith 1921; Parmenter 1921; Willcox et al. 1915). 

Though mostly qualitative, these studies have confirmed that the same organ systems are affected as those 

for acute-duration exposure. 

Intermediate-duration inhalation exposure of animals to intermittent high concentrations of 1,1,2,2-tetrachloroethane caused mortality and neurological and liver effects that are essentially acute in nature 

(Horiuchi et al. 1962). Information on effects of intermediate-duration inhalation exposure to lower 

concentrations of 1,1,2,2-tetrachloroethane is available from poorly reported studies in rats and rabbits 

(Kulinskaya and Verlinskaya 1972; Union Carbide Corporation 1947; Schmidt et al. 1972; Shmuter 1977; 

Truffert et al. 1977). These studies provide information on hepatic, reproductive, and other nonneurological effects. With the exception of the reproductive effects (Schmidt et al. 1972), these studies 

are inadequate for identifying a NOAEL or LOAEL due to insufficient data on incidence, magnitude, 

and/or severity of effects. 
 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 99 

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Intermediate-duration oral toxicity studies of 1,1,2,2-tetrachloroethane include a 21-day gavage study in 

rats (NTP 1996), a 16-day gavage study in mice (NTP 1993d), 6-week gavage studies in rats and mice 

(NCI 1978), and 15-day diet studies in rats and mice (NTP 2004a). These studies are mainly dose rangefinding studies that used small numbers of animals and had limited or no evaluations of clinical chemistry 

and histology. Additional information on the intermediate-duration oral toxicity of 1,1,2,2-tetrachloroethane is available from comprehensive 14-week dietary studies in rats and mice (NTP 2004a) that tested 

wider ranges of doses and varieties of end points than the studies summarized above. The NTP (2004a) 

study in rats found liver-related serum chemistry changes at 80 mg/kg/day and hepatocellular necrosis at 

170 mg/kg/day (NTP 2004a). Mice exposed for 14 weeks in the diet had similar liver effects at higher 

doses than the rats (NTP 2004a). Comprehensive neurological testing in the 14-week studies showed no 

effects in either species, indicating that the liver was more sensitive than the nervous system for 

intermediate-duration dietary exposure. The NTP (2004a) study in rats served as the basis for deriving an 

intermediate-duration oral MRL for 1,1,2,2-tetrachloroethane, as described in detail in Chapter 2 and 

Appendix A. 

Additional intermediate-duration oral studies are not necessary at this time. An intermediate-duration 

inhalation study in laboratory animals could be designed to provide information necessary to derive an 

intermediate-duration inhalation MRL for 1,1,2,2-tetrachloroethane. 

Chronic-Duration Exposure and Cancer. Information on the chronic inhalation toxicity of 

1,1,2,2-tetrachloroethane in humans is available from several occupational studies (Jeney et al. 1957; 

Lobo-Mendonca 1963; Minot and Smith 1921; Norman et al. 1981) that are inadequate for identification 

of effect levels due to limitations that include insufficient characterization of exposure levels, lack of 

control data, dermal exposures, and/or mixed chemical exposures. Although not sufficient for 

identification of effect levels or MRL derivation, the occupational studies provide limited supporting 

information on the neurotoxicity and hepatotoxicity of 1,1,2,2-tetrachloroethane. Chronic inhalation 

studies in animals have not been performed. 

The systemic effects of long-term repetitive oral exposure of mice and rats to 1,1,2,2-tetrachloroethane 

have been studied via gavage using several dose levels (NCI 1978). The NCI (1978) study identified 

LOAELs of 108 mg/kg/day for liver lesions in rats and a serious LOAEL of 284 mg/kg/day for lethal 

kidney lesions and reduced survival in mice. Derivation of a chronic oral MRL is precluded because 

lower LOAELs are identified in the more comprehensive and sensitive 14-week diet study in these 

species (NTP 2004a) used to derive the intermediate-duration MRL. 
 

 

 

 

 

 

 

 

 

 

 

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There is one study on the possible carcinogenic effect of 1,1,2,2-tetrachloroethane on humans via 

inhalation exposure (Norman et al. 1981), and there are oral studies of the effects on rats and mice (NCI 

1978). The human study was inconclusive and in the NCI (1978) study, liver tumors were found in mice 

after long-term oral exposure. Although this species has a high rate of spontaneous incidence of these 

tumors, the results in the mice are indicative of a potential carcinogenic risk in humans. 

There are no studies of the effect of chronic-duration dermal administration of 1,1,2,2-tetrachloroethane 

in humans or animals. Determination of the effect of chronic-duration dermal administration of 

1,1,2,2-tetrachloroethane to animals would be methodologically problematic due to inadvertent oral 

and/or inhalation exposures. Additionally, chronic-duration dermal exposure is unlikely for humans. 

Therefore, chronic-duration studies by this route are not recommended. 

Since humans are most likely to be exposed via the inhalation or oral routes, long-term animal studies that 

include a range of exposure levels for inhalation and oral exposure should be designed to better assess 

cancer and noncancer end points. Such studies would provide support to existing oral cancer data and 

facilitate derivation of an inhalation unit risk as well as chronic-duration inhalation and oral MRLs for 

1,1,2,2-tetrachloroethane. 

Genotoxicity. Information on the in vivo genotoxic effects of 1,1,2,2-tetrachloroethane is lacking for 

humans and limited for animals (see Table 3-4), although there are a number of in vitro tests of the 

mutagenicity of 1,1,2,2-tetrachloroethane (see Table 3-3). This type of data is not sufficient to determine 

if 1,1,2,2-tetrachloroethane is genotoxic in humans. In vivo testing and in vitro testing on human cell 

lines would help determine if 1,1,2,2-tetrachloroethane is genotoxic in humans. The known metabolism 

of 1,1,2,2-tetrachloroethane to reactive acid chlorides and/or free radical products suggests that genotoxic 

effects in humans and other mammals are possible. Based on observations of the mixed nature of results 

from available in vivo and in vitro genotoxicity tests and carcinogenicity bioassays and positive DNA 

binding data, additional well-designed genotoxicity testing is warranted. 

Reproductive Toxicity. There were no human reproductive toxicity studies reported for 

1,1,2,2-tetrachloroethane. The reproductive toxicity of 1,1,2,2-tetrachloroethane has not been adequately 

evaluated in animals because reproductive toxicity has not adequately been assessed using standard 

multiple-generation reproductive toxicity studies. After acute-duration inhalation exposure at 6,310 ppm, 

no effects on the testes, epididymes, ovaries, or uteruses were found in rats (NIOSH 1978). Similarly, an 
 

 

 

 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 101 

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intermediate-duration study by inhalation (Horiuchi et al. 1962) reported no effects on the testes in one 

monkey. Inhalation exposure to 1.9 ppm for 4 hours/day for 9 months had no reproductive effects in male 

mice; when mated with unexposed females, there were no significant changes in percentage of females 

having offspring, littering times, or offspring numbers, sex ratio, birth weight, or postnatal survival 

(Schmidt et al. 1972). The effect of oral exposure on male or female reproductive function has not been 

tested. Male rats that were exposed to 1,1,2,2-tetrachloroethane in the diet for 14 weeks had no adverse 

changes in sperm number or motility at 80 mg/kg/day (highest tested dose), although minimal to 

moderate atrophy of the testicular germinal epithelium, prostate gland, and seminal vesicle occurred at 

320 mg/kg/day (NTP 2004a). Reproductive effects in similarly exposed female rats included estrus 

alterations and minimal to mild uterine atrophy at 170 mg/kg/day, and clitoral gland atrophy and ovarian 

interstitial cell cytoplasmic alterations at 320 mg/kg/day (NTP 2004a). Body weight loss at 

320 mg/kg/day and reduced body weight gain at lower dose levels could have contributed to the effects 

observed in the male and female rats. There were no clear effects on histology of male or female 

reproductive tissues, sperm indices, or estrus cycle in mice exposed to dietary doses as high as 1,360– 

1,400 mg/kg/day for 14 weeks (NTP 2004a). Chronic-duration oral administration of 1,1,2,2-tetrachloroethane to rats and mice caused no increase in histological alterations in reproductive organs (NCI 1978). 

Due to apparently equivocal results from studies that examined various aspects of reproductive endpoints 

in 1,1,2,2-tetrachloroethane-exposed animals, and the lack of information regarding possible reproductive 

toxicity in humans, a well designed multiple-generation reproductive toxicity study in laboratory animals 

is needed to adequately assess the potential for 1,1,2,2-tetrachloroethane-induced reproductive toxicity. 

Developmental Toxicity. The developmental toxicity of 1,1,2,2-tetrachloroethane has not been 

adequately assessed. Information regarding the potential for 1,1,2,2-tetrachloroethane-induced 

developmental toxicity following inhalation or oral exposure is restricted to a single rat study by the 

inhalation exposure route (Schmidt et al. 1972) and one set of rat (NTP 1991a) and mouse (NTP 1991b) 

studies using oral administration. In the inhalation study, male rats were exposed to 1,1,2,2-tetrachloroethane and mated with unexposed females, and the F1 generation was observed for 12 weeks. No effects 

on the number of offspring per litter, neonatal body weight, offspring viability, or sex ratios were 

observed. No gross malformations in offspring were detected (Schmidt et al. 1972). In the oral (dietary) 

rat study, completely resorbed litters and significantly decreased fetal weights were reported (NTP 

1991a). However, because the oral treatment also resulted in dose-related significantly reduced food 

consumption and serious maternal body weight effects, a direct treatment-related developmental effect 

could not be discerned. Fetuses were not examined for malformations. In the oral (dietary) mouse study 

(NTP 1991b), the lowest exposure level (0.5% in the food; dose of approximately 987 mg/kg/day) 
 

 

 

 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 102 

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resulted in 14% decreased maternal body weight gain during the treatment period, but there were no 

indications of developmental effects with respect to number of implantation sites, number of resorptions, 

numbers of dead and live fetuses, or gravid uterine weight. Exposure at higher levels resulted in maternal 

death, precluding assessment of treatment-related developmental toxicity at the higher doses. 

Additional well-designed developmental toxicity studies that include comprehensive assessment of 

developmental toxicity end points at exposure levels below those resulting in serious maternal toxicity are 

needed to provide a better understanding of the potential developmental toxicity of 1,1,2,2-tetrachloroethane. 

Immunotoxicity. There is a lack of useful information on the effects of 1,1,2,2-tetrachloroethane on 

the immune system in humans, and the information available from animal studies in this area is very 

limited. The human studies were dated, lacked information on the dose received and duration of 

exposure, and reported only gross effects on the appearance of the spleen following acute ingestion 

(Coyer 1944; Elliott 1933; Hepple 1927). No histopathological changes were noted in the spleens of rats 

that inhaled 100 ppm 1,1,2,2-tetrachloroethane for 6 hours (Deguchi 1972). In a 14-week dietary study of 

rats, pigmentation of the spleen was increased in males receiving 1,1,2,2-tetrachloroethane at doses 

≥80 mg/kg/day and in females receiving doses ≥170 mg/kg/day; high incidences (70–100%) of atrophy in 

the spleen (red pulp and lymphoid follicle) of both sexes were noted at 320 mg/kg/day (NTP 2004a). No 

gross or histological alterations were seen in the spleen or lymph nodes of rats and mice exposed to 

1,1,2,2-tetrachloroethane at doses up to 284 mg/kg/day for 78 weeks. Rabbits intermittently exposed to 

1.5 ppm of 1,1,2,2-tetrachloroethane vapor for 8 months and then immunized with a typhoid vaccine 

showed a decrease in titers and an increase in the electrophoretic mobility of the specific antibodies 

(Shmuter 1977); however, these results are considered of questionable toxicological significance and 

study details were poorly reported. Since immunological end points are known to be very sensitive 

indicators of the toxicity of many chemicals, a battery of immunological function tests in animals would 

be helpful in clarifying whether 1,1,2,2-tetrachloroethane is an immunotoxicant. 

There are no data on sensitization as a result of exposure to 1,1,2,2-tetrachloroethane by any route in 

humans or animals. Dermal sensitization tests in animals may be useful based on potential for dermal 

exposure from soil and water near hazardous waste sites. 

Neurotoxicity. Information on the neurotoxicity of acute inhalation exposure to 1,1,2,2-tetrachloroethane in humans comes from a poorly reported experimental study in which two volunteers self-inhaled 
 

 

 

 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 103 

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various concentrations of the chemical for up to 30 minutes (Lehmann and Schmidt-Kehl 1936). The 

results of this study suggest that 3 ppm was the odor detection threshold, 13 ppm was tolerated without 

effect for 10 minutes, and 146 ppm for 30 minutes or 336 ppm for 10 minutes caused irritation of the 

mucous membranes, pressure in the head, vertigo, and fatigue. Other early human reports similarly found 

that clinical signs of high-dose acute inhalation exposure to 1,1,2,2-tetrachloroethane include drowsiness, 

nausea, headache, and weakness, and at extremely high concentrations, unconsciousness and respiratory 

failure (Coyer 1944; Hamilton 1917). In animals, signs of acute central nervous system toxicity (e.g., 

incoordination, loss of reflexes, labored respiration, prostration, and loss of consciousness) typically 

proceeded death, which occurred at concentrations of 1,000–1,253 ppm for 4–6 hours in rats (Carpenter et 

al. 1949; Schmidt et al. 1980b), 1,168–5,900 ppm for 1.5–3 hours in mice (Horiuchi et al. 1962; 

Pantelitsch 1933), and 5,050–6,310 ppm for 30 minutes in rats and guinea pigs (NIOSH 1978). Exposure 

to 576 ppm for 30 minutes caused reduced activity and alertness in rats and guinea pigs (NIOSH 1978). 

The effective concentration for a 50% decrease in spontaneous motor activity in rats was 360 ppm for a 

6-hour exposure (Horvath and Frantik 1973). Intermediate-duration inhalation exposure to intermittent 

high concentrations of 1,1,2,2-tetrachloroethane caused neurological effects that are essentially acute in 

nature. Rats that were exposed to 9,000 ppm for 2 hours/day 2–3 times/week for 29 days became 

hyperactive within the first few minutes of each exposure, followed by ataxic gait within approximately 

20 minutes and eventual near-complete loss of consciousness within 1–1.5 hours (Horiuchi et al. 1962). 

A monkey that was exposed to 1,974 ppm for 2 hours/day, 6 days/week for 190 exposures in 9 months 

developed, beginning at the fifteenth exposure, near-complete unconsciousness for 20–60 minutes after 

each exposure (Horiuchi et al. 1962). 

Information on the neurotoxicity of oral exposure to 1,1,2,2-tetrachloroethane in humans is available from 

several case reports. People who intentionally ingested lethal amounts usually lost consciousness within 

approximately 1 hour and died 3–20 hours postingestion (Elliott 1933; Forbes 1943; Hepple 1927; 

Lilliman 1949; Mant 1953; Sherman 1953). No deaths occurred in 11 patients who were accidentally 

given an estimated oral dose of 68–118 mg/kg as medicinal treatment for hookworm, although they 

experienced loss of consciousness and other clinical signs of narcosis that included shallow breathing, 

faint pulse, and pronounced lowering of blood pressure (Sherman 1953; Ward 1955). In animals, lethargy 

and central nervous system depression occurred in rats gavaged with 270–300 mg/kg/day for 1–12 days 

(Hanley et al. 1988; NTP 1993a, 1993b) or 208 mg/kg/day for 21 days (NTP 1996). Information on 

neurological effects of lower acute oral doses is limited to a poorly reported rat study in which a single 

gavage dose of 100 mg/kg caused ataxia and 50 mg/kg caused decreased passive avoidance to an electric 

shock, possibly due to an increased threshold of shock perception due to a subtle anesthetic effect (Wolff 
 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 104 

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1978). No clinical signs of neurotoxicity were observed in 14-week dietary studies in which rats and 

mice were exposed to doses as high as 320 and 1,400 mg/kg/day, respectively (NTP 2004a). 

Comprehensive neurological evaluations (functional observational batteries) in the 14-week studies 

showed no effects in either species, although 80 mg/kg/day was the highest tested dose in the rats. 

Tests to show the site of action would be helpful in determining exactly how 1,1,2,2-tetrachloroethane 

affects the nervous system of humans. 

Epidemiological and Human Dosimetry Studies. Available epidemiological data are restricted 

to a limited report in which the cancer mortality of service men exposed to 1,1,2,2-tetrachloroethane 

during World War II was assessed (Norman et al. 1981). The exposure was presumed to be mostly by 

inhalation, but dermal exposure was also possible and precise dosimetry was unknown. Over 

1,000 subjects were used in each of the control and exposed groups. There were only very slightly 

elevated incidences (not statistically significant) of cancer of the genital organs, as well as leukemia and 

lymphoma. Because environmental levels of 1,1,2,2-tetrachloroethane measured in the United States are 

relatively low (<10 ppt in ambient air and <25 ppb in water), exposure of the general population is 

expected to be very low. It is possible that humans who live near hazardous waste sites or facilities that 

produce or use 1,1,2,2-tetrachloroethane may be exposed to higher levels of this substance in the air, 

water, and soil. If populations with higher levels of exposure to 1,1,2,2-tetrachloroethane are identified, 

epidemiological and biomonitoring studies should be conducted to assess exposure levels and 

neurological, liver, and kidney effects, as well as potential reproductive, developmental, and cancer 

endpoints, with particular emphasis on effects of chronic-duration low-level exposures. 

Biomarkers of Exposure and Effect. 

Exposure. Since the metabolites of 1,1,2,2-tetrachloroethane are known, and can be measured in the 

urine of rats (Yllner 1971), it is possible to measure these metabolites in urine to see if a person has been 

exposed to 1,1,2,2-tetrachloroethane. However, these metabolites are common to several types of 

chlorinated ethanes and would not be specific for exposure to 1,1,2,2-tetrachloroethane. Also, 

1,1,2,2-tetrachloroethane is metabolized and excreted rather quickly, and the test might only indicate 

whether the person had been exposed in the last few days. It would be useful to ascertain if 

measurements of parent compounds and metabolites in excreta or in biopsy samples (e.g., adipose) could 

be used to quantitate the body burden associated with exposures to known concentrations of 1,1,2,2-tetrachloroethane. 
 

 

 

 

 

 

 

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Effect. 1,1,2,2-Tetrachloroethane may cause liver damage. In cases where humans have been exposed to 

high levels of 1,1,2,2-tetrachloroethane, it may be possible to correlate urinary metabolites with serum 

indicators of liver malfunction. Although this is a data need, the metabolites would not be specific for 

1,1,2,2-tetrachloroethane. 

Absorption, Distribution, Metabolism, and Excretion. In both humans (Lehmann and SchmidtKehl 1936; Morgan et al. 1970) and laboratory animals (Hanley et al. 1988), 1,1,2,2-tetrachloroethane is 

well absorbed after acute-duration inhalation exposure. While studies in which the quantitation of 

absorption following oral exposure was measured in humans were not available, the profound effects 

following ingestion of 1,1,2,2-tetrachloroethane indicate that appreciable amounts are absorbed by this 

route also. This is consistent with the data from animal studies, which indicate that oral doses are mostly 

absorbed (Milman et al. 1984; Mitoma et al. 1985). No studies were located regarding absorption 

following dermal exposure in humans. Only limited information was found regarding the distribution of 

1,1,2,2-tetrachloroethane following inhalation, oral, or dermal exposure in humans and animals. High 

levels of binding of 1,1,2,2-tetrachloroethane equivalents to hepatic proteins were found in rats and mice 

following oral dosing. 1,1,2,2-Tetrachloroethane is extensively metabolized in animals and excreted 

chiefly as metabolites in urine and breath (Ikeda and Ohtsuji 1972; Mitoma et al. 1985; Yllner 1971). 

Modern techniques employing mass spectrometry and/or nuclear magnetic resonance coupled with high 

resolution chromatographic methods to provide unambiguous structural identification were used only in a 

few recent studies. Unfortunately, the emphasis in those studies was the elucidation of particular 

mechanisms of reactive intermediate metabolite formation. A more broadly based evaluation of the 

formation of nontoxic or less toxic metabolites was not fully pursued. Fuller studies, such as that of 

Yllner (1971), employed less rigorous characterization methodology and structural assignments of 

metabolites made are not definitive. Metabolic pathways, and rates and patterns of distribution and 

excretion may be different following oral exposure than following inhalation or dermal exposure. 

Differences in metabolism may account for differences in toxicity following exposure by these routes. 

Thus, further studies in animals of the rate and extent of absorption and excretion, of distribution, and of 

metabolism following exposure by all three routes, and in vitro studies to elucidate metabolic pathways, 

would provide the information to fully characterize the pharmacokinetics of 1,1,2,2-tetrachloroethane in 

animals. 
 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 106 

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Comparative Toxicokinetics. PBPK modeling of the kinetics of 1,1,2,2-tetrachloroethane in rats 

exposed by inhalation has been performed by Gargas and Andersen (1989). Data on comparative 

toxicokinetics in rats and mice exposed to 1,1,2,2-tetrachloroethane by intermediate-duration inhalation 

exposure are available (Mitoma et al. 1985). Mice metabolized 1,1,2,2-tetrachloroethane at roughly twice 

the rate of rats given similar doses, and the amount of protein bound equivalents were higher. Further 

studies in these and other species may provide information to account for differences in toxicity among 

animal species. There are limited human metabolism and excretion data. A single study has shown that 

3% of inhaled 1,1,2,2-tetrachloroethane was excreted in the breath, and that the urinary excretion rate was 

0.015% absorbed dose/minute (Morgan et al. 1970). Analysis of levels of metabolites in the urine of 

people with known exposure is a data need that could provide knowledge of metabolic pathways in 

humans. Additionally, biochemically viable human tissues, including liver, are now routinely available 

for metabolism studies. In this way, the metabolism of 1,1,2,2-tetrachloroethane in humans of differing 

genetic background and life style (e.g., consumers of alcohol or tobacco) can be determined in 

microsomes and precision-cut tissue slices. This information may allow accurate prediction of the 

metabolism of 1,1,2,2-tetrachloroethane in humans. Qualitative comparisons of human metabolites with 

those of animals could help to fill a data need by identifying the most appropriate animal species to serve 

as a model for predicting toxic effects in humans and studying the mechanism of action. PBPK models 

could be developed and used to estimate 1,1,2,2-tetrachloroethane target tissue levels following 

environmentally-relevant exposures. These PBPK models would be useful tools for dose-response health 

assessments. 

Methods for Reducing Toxic Effects. No studies were located regarding the mechanism of 

absorption in humans or animals after inhalation, oral, or dermal exposure to 1,1,2,2-tetrachloroethane. 

Carbon and castor oil have been shown to increase the survival times in rats administered oral doses of 

1,1,2,2-tetrachloroethane (Laass 1973a, 1973b, 1974a, 1974b), but data are needed on the actual 

mechanisms of absorption and distribution of this chemical in the body. 1,1,2,2-Tetrachloroethane is 

metabolized to reactive toxic acyl chlorides and to free radicals. No treatments were described that 

mitigate the health effects that result from exposure to the compound. However, alcohol and acetone, 

inducers of cytochrome P-450 isoenzyme 2E1 increased the metabolism of 1,1,2,2-tetrachloroethane and 

intensified the toxic effects (Gohlke and Schmidt 1972; Sato et al. 1980). Studies to determine methods 

for blocking the absorption or increasing the excretion of 1,1,2,2-tetrachloroethane would be helpful to 

better define methods to reduce the toxic effects of the chemical. 
 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 107 

3. HEALTH EFFECTS 

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. 

No information was located regarding potential age-related differences in susceptibility to 1,1,2,2-tetrachloroethane in humans or animals. A well-designed animal study would provide valuable information 

regarding the potential for age-related susceptibility to 1,1,2,2-tetrachloroethane. Such a study could be 

designed to assess developmental neurotoxicity since the nervous system is one of the known targets of 

1,1,2,2-tetrachloroethane toxicity. 

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 

No ongoing studies pertaining to 1,1,2,2-tetrachloroethane were located in a search of the Federal 

Research in Progress database (FEDRIP 2006). 
 

1,1,2,2-TETRACHLOROETHANE 108 

3. HEALTH EFFECTS 

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1,1,2,2-TETRACHLOROETHANE 109 

4. CHEMICAL AND PHYSICAL INFORMATION 

4.1 CHEMICAL IDENTITY 

Information regarding the chemical identity of 1,1,2,2-tetrachloroethane is located in Table 4-1. 

4.2 PHYSICAL AND CHEMICAL PROPERTIES 

Information regarding the physical and chemical properties of 1,1,2,2-tetrachloroethane is located in 

Table 4-2. 
 

1,1,2,2-TETRACHLOROETHANE 110 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-1. Chemical Identity of 1,1,2,2-Tetrachloroethane 

Characteristics Information References 

Chemical name 1,1,2,2-Tetrachloroethane Lide 2005 

Synonyms Tetrachloroethane; acetylene ChemID 2004 

tetrachloride; dichloro-2,2­

dichloroethane; 

s-tetrachloroethane 

Trade names Bonoform, Cellon, Westron, ChemID 2004; HSDB 2006 

Acetosol 

Chemical formula C2H2Cl4 O’Neil et al. 2001 

Chemical structure Cl Cl Lide 2005 

Cl Cl 

Identification numbers: 

CAS registry 79-34-5 ChemID 2004 

NIOSH RTECS KI8575000 RTECS 2006 

EPA hazardous waste U209 RTECS 2006 

OHM/TADS 8100014 HSDB 1995 

DOT/UN/NA/IMDG shipping UN 1702; IMDG 6.1 HSDB 2006 

HSDB 123 HSDB 2006 

NCI NCI-C03554 RTECS 2006 

CAS = Chemical Abstracts Service; DOT/UN/NA/IMDG -Department of Transportation/United Nations/North 

America/ Intergovernmental Maritime Consultive Organization; EPA = Environmental Protection Agency; 

HSDB = Hazardous Substance Data Bank; NCI = National Cancer Institute; NIOSH = National Institute for 

Occupational Safety and Health; OHM/TADS = Oil and Hazardous Materials/Technical Assistance Data Base; 

RTECS = Registry of Toxic Effects of Chemical Substances 
 

 

1,1,2,2-TETRACHLOROETHANE 111 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of 1,1,2,2-Tetrachloroethane 

Property Tetrachloroethane References 

Molecular weight 167.85 O’Neil et al. 2001 

Color Colorless Lewis 2001 

Physical state Liquid Lewis 2001 

Melting point -42.4 °C O’Neil et al. 2001 

Boiling point 145.2 °C Lide 2005 

Density (20 °C) 1.6 Lewis 2001 

Odor Sweetish, suffocating, chloroform-like O’Neil et al. 2001 

Odor threshold 

Water 0.5 ppm Amoore and Hautala 1983 

Air 1.5 ppm Amoore and Hautala 1983 

Solubility 

Water at 25 °C 2.83x103 mg/L Horvath et al. 1999 

Organic solvents Miscible with methanol, ethanol, 

benzene, ether, petroleum ether, 

carbon tetrachloride, chloroform, 

carbon disulfide, dimethylformamide, 

oils 

O’Neil et al. 2001 

Partition coefficients 

Log octanol/water 2.39 Hansch et al. 1995 

Koc 46, 83, 118, 173, 216, 240 Borisover and Graber 1997; 

Chiou et al. 1979; Chu and Chan 

2000; Valsaraj et al. 1999 

Vapor pressure 

25 °C 4.62 mmHg AIChE 1995 

Henry’s law constant 

atm/m3-molecule at 25 °C 3.67x10-4 atm-m3/mol Leighton and Calo 1981 

Conversion factors 

ppm (v/v) to mg/m3 in air 

(20 °C) 

mg/m3 to ppm (v/v) in air 

(20 °C) 

1 ppm=6.98 mg/m3 

1 mg/m3=0.14 ppm 

Verschueren 2001 

Verschueren 2001 

Bioconcentration factor 

BCF 8, 2 ASTER 1995; Barrows et al. 

1980 
1,1,2,2-TETRACHLOROETHANE 112 

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1,1,2,2-TETRACHLOROETHANE 113 

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

5.1 PRODUCTION 

1,1,2,2-Tetrachloroethane as an end-product was formerly produced in the United States only by the 

Specialty Materials Division of Eagle-Picher Industries in Lenexa, Kansas (SRI 1988). By the late 1980s, 

this facility had been sold to the Vulcan Materials Company, and production was discontinued at the 

Kansas facilities (Montgomery and Welkom 1990; SRI 1992, 1993). Approximately 440 million pounds 

(199.5 million kg) of 1,1,2,2-tetrachloroethane were produced in the United States in 1967 (Konietzko 

1984). Production declined markedly thereafter, falling to an estimated 34 million pounds (15.4 million 

kg) by 1974. The production volumes of 1,1,2,2-tetrachloroethane reported by U.S. manufacturers in 

1986, 1990, 1994, and 1998 have fluctuated within a range of <1 million to 50 million pounds (IUR 

2002). The production volume reported in 2002 was within the range of <1 million to 10 million pounds 

(IUR 2002). 

Commercial production of 1,1,2,2-tetrachloroethane as an end-product has apparently ceased in the 

United States. This parallels patterns in Canada, where the last plant to manufacture 1,1,2,2-tetrachloroethane as an end-product ceased operations by 1985 (CEPA 1993). Any remaining production in the 

United States or Canada at the present time would involve 1,1,2,2-tetrachloroethane generated for on-site 

uses as a chemical intermediate, as a trace constituent with other chemicals, or as part of a waste stream in 

releases to the environment. 

1,1,2,2-Tetrachloroethane can be produced by the catalytic addition of chlorine to acetylene (Rossberg et 

al. 2005); it may also be produced by the direct chlorination or oxychlorination of ethylene or 

1,2-dichloroethane (Archer 1979; Rossberg et al. 2005). In most cases, 1,1,2,2-tetrachloroethane was not 

isolated to form an end-product, but was immediately thermally cracked to yield desired chemicals such 

as trichloroethylene, tetrachloroethylene, and 1,2-dichloroethylene (Archer 1979). 1,1,2,2-Tetrachloroethane may be produced as a by-product in the manufacture of chemicals such as 1,1,1- and 

1,1,2-trichloroethane (Rossberg et al. 2005). Section 5.3 summarizes information on several chemicals 

with which 1,1,2,2-tetrachloroethane can appear as a trace constituent. 

Table 5-1 lists the facilities in each state that process 1,1,2,2-tetrachloroethane, the intended use, and the 

range of maximum amounts of 1,1,2,2-tetrachloroethane that are stored on site. Current production is for 
 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 114 

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

Table 5-1. Facilities that Produce, Process, or Use 1,1,2,2-Tetrachloroethane 

Minimum Maximum 

Number of amount on site amount on site 

Statea facilities in poundsb in poundsb Activities and usesc 

AR 3 1,000 99,999 10, 12 

CA 2 100 999,999 9, 11 

CO 7 1,000 99,999 1, 2, 5, 6, 11, 12, 13 

CT 1 1,000 9,999 12 

FL 2 100 99,999 12 

KS 3 100 9,999 1, 5, 9, 12 

KY 4 10,000 9,999,999 1, 3, 5, 6 

LA 29 100 49,999,999 1, 2, 3, 4, 5, 6, 12, 13 

MI 2 0 99,999 5, 7, 12 

MN 1 10,000 99,999 11 

MO 1 1,000 9,999 12 

NC 1 100,000 999,999 7 

NE 2 1,000 99,999 12 

NJ 2 1,000 99,999 10 

NY 1 10,000 99,999 12 

OH 2 1,000 999,999 7, 9, 12 

PA 1 10,000 99,999 10 

SC 3 10,000 99,999 2, 3, 4, 7, 9 

TN 6 10,000 99,999 2, 3, 4, 7, 8, 10, 12 

TX 25 0 9,999,999 1, 2, 3, 5, 6, 11, 12, 13, 14 

VA 1 100 999 12 

AR 3 1,000 99,999 10, 12 

CA 2 100 999,999 9, 11 

CO 7 1,000 99,999 1, 2, 5, 6, 11, 12, 13 

CT 1 1,000 9,999 12 

FL 2 100 99,999 12 

KS 3 100 9,999 1, 5, 9, 12 

KY 4 10,000 9,999,999 1, 3, 5, 6 

LA 29 100 49,999,999 1, 2, 3, 4, 5, 6, 12, 13 

MI 2 0 99,999 5, 7, 12 

MN 1 10,000 99,999 11 

MO 1 1,000 9,999 12 

NC 1 100,000 999,999 7 

NE 2 1,000 99,999 12 

NJ 2 1,000 99,999 10 

NY 1 10,000 99,999 12 

OH 2 1,000 999,999 7, 9, 12 

PA 1 10,000 99,999 10 
 

 

 

1,1,2,2-TETRACHLOROETHANE 115 

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

Table 5-1. Facilities that Produce, Process, or Use 1,1,2,2-Tetrachloroethane 

Statea 

Number of 

facilities 

Minimum 

amount on site 

in poundsb 

Maximum 

amount on site 

in poundsb Activities and usesc 

SC 

TN 

3 

6 

10,000 

10,000 

99,999 

99,999 

2, 3, 4, 7, 9 

2, 3, 4, 7, 8, 10, 12 

TX 25 0 9,999,999 1, 2, 3, 5, 6, 11, 12, 13, 14 

VA 1 100 999 12 

a

Post office state abbreviations used b

Amounts on site reported by facilities in each state 

c

Activities/Uses: 

1. Produce 

2. Import 

3. Onsite use/processing 

4. Sale/Distribution 

5. Byproduct 

6. Impurity 

7. Reactant 

8. Formulation Component 

9. Article Component 

10. Repackaging 

11. Chemical Processing Aid 

12. Manufacturing Aid 

13. Ancillary/Other Uses 

14. Process Impurity 

Source: TRI05 2007 (Data are from 2005) 
 

 

 

 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 116 

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

on-site uses or as a by-product, so that the phrase "manufacture" in the table heading does not imply 

production for sale as a commercial end-product. The data listed in Table 5-1 are derived from the Toxics 

Release Inventory (TRI) and refer to facilities operating in 2005 (TRI05 2007). Only certain types of 

facilities are legally required to report, and therefore, this is not an exhaustive list (TRI05 2007). 

5.2 IMPORT/EXPORT 

Limited data pertaining to the import or export of 1,1,2,2-tetrachloroethane were located in the available 

literature. Imports in 1982 totaled 65,500 kg (144,100 pounds) (HSDB 1996). Present tariff-setting and 

record-keeping practices combine 1,1,2,2-tetrachloroethane with other chemicals (USITC 1994). Total 

U.S. imports and exports of hexachloroethane and tetrachloroethane combined were 128,865 kg 

(283,503 pounds) and 11,282,409 kg (24,821,300 pounds) in 2005, respectively (U.S. Department of 

Commerce 2006). 

5.3 USE 

In the past, the major use for 1,1,2,2-tetrachloroethane was in the production of trichloroethylene, 

tetrachloroethylene, and 1,2-dichloroethylene (Archer 1979). It was also used as a solvent, in cleaning 

and degreasing metals, in paint removers, in varnishes and lacquers, in photographic films, and as an 

extractant for oils and fats (Lewis 2001). Although at one time, it could be used as an insecticide, 

fumigant, and weed killer (Lewis 2001), it presently is not registered for any of these purposes. It was 

once used as an ingredient in an insect repellent, but registration was canceled in the late 1970s. With the 

availability of less toxic solvents and the development of new processes for manufacturing chlorinated 

ethylenes, the manufacture of 1,1,2,2-tetrachloroethane as a commercially marketed end-product has 

steadily declined in the United States and now appears to have ceased (HSDB 2006). A similar trend is 

reported in Canada (CEPA 1993). 

1,1,2,2-Tetrachloroethane can still appear as a chemical intermediate in the production of a variety of 

other common chemicals. Trace amounts of 1,1,2,2-tetrachloroethane may be introduced into the 

environment as these other chemicals are produced, or it may appear as a minor impurity in the endproducts. Therefore, it is helpful to know how some of these other chemicals are related to 1,1,2,2-tetrachloroethane (e.g., CEPA 1993; Harte et al. 1991). Several of these chemicals, including 

trichloroethylene (TCE); 1,1,2-trichloroethane; 1,2-dichloroethene (DCE or vinylidene chloride); 
 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 117 

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

tetrachloroethylene (perchloroethylene, PCE, or PERC); vinyl chloride; 1,2-dichloroethane (ethylene 

dichloride [EDC]); and 1,1,1-trichloromethane (methyl chloroform), are the subjects of separate ATSDR 

profiles, which are available through the internet (http://www.atsdr.cdc.gov/toxpro2.html). 

5.4 DISPOSAL 

1,1,2,2-Tetrachloroethane disposal should follow the Resource Conservation and Recovery Act (RCRA) 

regulations appropriate for halogenated organic compound (HOC) wastes, which are likely to contain 

>1,000 ppm of HOCs (EPA 2006d, 2006e). Selection of an appropriate technology for waste treatment 

and disposal depends on the RCRA waste code number. RCRA defines five main categories of wastes. 

Waste code U209 is specifically assigned to 1,1,2,2-tetrachloroethane, but wastes containing 1,1,2,2-tetrachloroethane could be assigned to one or more of 25 halogenated organic wastes under the RCRA U and 

P waste series. 

For these U and P series wastes, the EPA has proposed three treatment technologies as alternative Best 

Demonstrated Available Technology (BDAT) treatment standards: (1) wet air oxidation followed by 

carbon adsorption; (2) chemical oxidation followed by carbon adsorption; or (3) incineration of waste 

waters. The BDAT for these HOC waste types is incineration. Industrial boilers or furnaces that function 

like waste disposal incinerators (e.g., cement kilns) may also substitute the combustible wastes for their 

normal fuel stocks. However, EPA does not believe that fuel substitution is a viable alterative for the 

majority of class U ("off-spec" materials that may contain impurities or mixtures of other wastes) HOC 

products. Chapter 8 of this profile provides a comprehensive overview of federal or state laws and 

regulations related to 1,1,2,2-tetrachloroethane. 

The following categories of hazardous wastes include 1,1,2,2-tetrachloroethane as a hazardous 

constituent: 

•	 process waste from the production of certain chlorinated aliphatic hydrocarbons (containing 

chains of one to five carbons); 

•	 distillation light ends, spent filters, and spent desiccant generated in the production of certain 

chlorinated aliphatic hydrocarbons; 

•	 wastes from the production of ethylene dichloride, vinyl chloride, trichloroethylene, 

perchloroethylene, chlorine, and 1,1,1-trichloroethane; and 
 

 

1,1,2,2-TETRACHLOROETHANE 118 

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

•	 off-specification 1,1,2,2-tetrachloroethane (i.e., 1,1,2,2-tetrachloroethane that does not meet 

desired chemical purity). 

Only one of these categories of wastes (process waste from the production of chlorinated aliphatic 

hydrocarbons) has an EPA-prescribed treatment standard before land disposal. Such wastes must be 

treated by incineration to comply with the restrictions. The other waste categories have concentrationbased standards that must be achieved before being sent to a RCRA-permitted land disposal facility (EPA 

2006e). The waste streams generated from the manufacture of vinyl chloride and ethylene dichloride 

have been noted in studies in both the United States and Canada to contain high levels of 1,1,2,2-tetrachloroethane (CEPA 1993). These waste streams are currently treated to recover and recycle many types 

of organic products prior to incineration, but trace amounts of 1,1,2,2-tetrachloroethane will remain, 

contributing to atmospheric emissions during the incineration disposal process, even assuming rates of 

destruction in excess of 99% (CEPA 1993). 
 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 119 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.1 OVERVIEW 

1,1,2,2-Tetrachloroethane has been identified in at least 329 of the 1,699 hazardous waste sites that have 

been proposed for inclusion on the EPA National Priorities List (NPL) (HazDat 2008). However, the 

number of sites evaluated for 1,1,2,2-tetrachloroethane is not known. The frequency of these sites can be 

seen in Figure 6-1. 

1,1,2,2-Tetrachloroethane is a synthetic chemical and is not known to occur naturally in the environment 

(IARC 1979). This chemical has been used as an intermediate in the production of chlorinated ethenes, as 

an industrial solvent and extractant, and as an ingredient in a few pesticide preparations. Its production as 

an end-product declined markedly after the late 1960s, and by the early 1990s, its manufacture as an endproduct had ceased both in the United States and in Canada (CEPA 1993). Therefore, current releases of 

1,1,2,2-tetrachloroethane are limited to fugitive emissions or discharges during its production and use as a 

chemical intermediate or during its formation as a byproduct. 

1,1,2,2-tetrachloroethane is released primarily to the atmosphere and to surface water; very small amounts 

are now being land-applied. If released onto soil, some of the chemical would be expected to volatilize, 

with the remainder leaching into the subsurface soil profile and, possibly, into groundwater. 

1,1,2,2-Tetrachloroethane is not expected to adsorb to soils and sediments based on measured Koc values 

ranging from 46 to 240 (Borisover and Graber 1997; Chiou et al. 1979; Chu and Chan 2000; Swann et al. 

1983; Valsaraj et al. 1999). If 1,1,2,2-tetrachloroethane is released to surface water, most of it would 

volatilize based on estimated volatilization half-lives of 6.9 hours to 6.1 days (Leighton and Calo 1981; 

Thomas 1990), with the remainder dissolving in water where it would undergo degradation through 

hydrolysis. In groundwater, the major degradation processes involve anaerobic biodegradation and 

chemical hydrolysis. Chemical hydrolysis is very sensitive to pH and is much faster under basic or 

neutral conditions. 1,1,2,2-Trichloroethylene is the primary metabolite of chemical hydrolysis. Measured 

half-lives for the chemical hydrolysis of 1,1,2,2-tetrachloroethane at neutral pHs range from 29 to 

102 days. Anaerobic biodegradation proceeds by hydrogenolysis, dichloroelimination, or dehydrochlorination; products of biodegradation include 1,2-dichloroethylene, 1,1,2-trichloroethane, 1,2-dichloroethane, and the highly toxic vinyl chloride. Bioconcentration of this substance in aquatic organisms is 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 121 

6. POTENTIAL FOR HUMAN EXPOSURE 

expected to be low based on measured BCF values of 2 and 8 (ASTER 1995; Barrows et al. 1980; Franke 

et al. 1994). 

In the atmosphere, 1,1,2,2-tetrachloroethane is removed primarily via reaction with photochemically 

generated hydroxyl radicals. The half-life of this reaction is 54 days, calculated using a measured rate 

constant (Tosato et al. 1991). Atmospheric removal may also occur through washout by precipitation; 

however, most 1,1,2,2-tetrachloroethane removed by this mechanism will likely reenter the atmosphere 

by volatilization. Slow diffusion into the stratosphere will also occur, where 1,1,2,2-tetrachloroethane 

may participate in reactions that generate ozone-destroying chlorine radicals. However, this chemical is 

not expected to contribute significantly to the destruction of the ozone layer since <1% of the 

tropospheric 1,1,2,2-tetrachloroethane is expected to reach the stratosphere (EPA 1979; WHO 1998). 

Reported average concentrations of 1,1,2,2-tetrachloroethane measured in ambient air from both urban 

and rural locations across the United States are generally <10 ppt (Brodzinsky and Singh 1982; Class and 

Ballschmiter 1986; EPA 1988c; Pratt et al. 2000). However, average urban air concentrations as high as 

57 ppb have been reported (Harkov et al. 1981, 1983; Lioy et al. 1985; Singh et al. 1981, 1982). 

1,1,2,2-Tetrachloroethane was detected in approximately 43% of 12,476 water samples (surface water and 

groundwater) listed in the STORET database (EPA 2006f). However, only 3% of the samples contained 

1,1,2,2-tetrachloroethane above the quantitation limit (unspecified). The range, mean, and median of 

quantifiable 1,1,2,2-tetrachloroethane concentrations were 0.1–25, 0.6, and 0.5 ppb, respectively. 

1,1,2,2-Tetrachloroethane was detected in <0.001% of 166,559 public water system samples collected in 

the United States between 1993 and 1997 (EPA 2001b). Limited monitoring data are available for 

1,1,2,2-tetrachloroethane in soil or sediment. The existing data indicate that this substance is not widely 

detected in these media (EPA 2006f; Krill and Sonzogni 1986; Shilling 1985; Westrick et al. 1984). 

1,1,2,2-Tetrachloroethane has not been detected in table-ready foods (FDA 2005b). 

Based on the low levels of 1,1,2,2-tetrachloroethane measured in the environment and the decreased use 

of this substance in nonindustrial settings, exposure of the general population to 1,1,2,2-tetrachloroethane 

is expected to be very low. However, individuals located near hazardous waste sites or facilities where 

1,1,2,2-tetrachloroethane is used as a chemical intermediate may be exposed to this substance by 

inhalation of contaminated air, by ingestion of contaminated drinking water, or by dermal contact with 

contaminated soil. Occupational exposures are expected to occur primarily via inhalation and dermal 

contact. 
 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 122 

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 2005). This is not an exhaustive list. 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 included in Standard Industrial Classification (SIC) Codes 10 (except 1011, 

1081, and 1094), 12 (except 1241), 20–39, 4911 (limited to facilities that combust coal and/or oil for the 

purpose of generating electricity for distribution in commerce), 4931 (limited to facilities that combust 

coal and/or oil for the purpose of generating electricity for distribution in commerce), 4939 (limited to 

facilities that combust coal and/or oil for the purpose of generating electricity for distribution in 

commerce), 4953 (limited to facilities regulated under RCRA Subtitle C, 42 U.S.C. section 6921 et seq.), 

5169, 5171, and 7389 (limited S.C. section 6921 et seq.), 5169, 5171, and 7389 (limited to facilities 

primarily engaged in solvents recovery services on a contract or fee basis); 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 2005). 

6.2.1 Air 

Estimated releases of 3,170 pounds (1.4 metric tons) of 1,1,2,2-tetrachloroethane to the atmosphere from 

20 domestic manufacturing and processing facilities in 2005, accounted for about 90% of the estimated 

total environmental releases from facilities required to report to the TRI (TRI05 2007). These releases are 

summarized in Table 6-1. 

1,1,2,2-Tetrachloroethane is expected to be released into the air during the process of manufacturing 

trichloroethylene and other chlorinated hydrocarbons (WHO 1998). It may also be emitted from 

hazardous waste landfills (Harkov et al. 1987). In the past, 1,1,2,2-tetrachloroethane may have been 

released to the air during its use as a metal degreasing agent; as a paint, varnish, and rust remover; and as 

an extractant, solvent, and chemical intermediate (Lewis 2001). However, these are no longer expected to 

be important sources of release since the use of 1,1,2,2-tetrachloroethane as an end-product appears to 

have ceased in the United States. 

1,1,2,2-Tetrachloroethane was one of the 10 most prevalent chlorinated chemicals found in solvent wastes 

that were incinerated each year prior to 1980 (Travis et al. 1986). A study was performed to ascertain the 

annual emissions of these chlorinated chemicals from a hypothetical 4,400 kw rotary kiln incinerator, 
 

 

1,1,2,2-TETRACHLOROETHANE 123 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-1. Releases to the Environment from Facilities that Produce, Process, or
 

Use 1,1,2,2-Tetrachloroethanea
 

Reported amounts released in pounds per yearb 

Total release 

Statec RFd Aire Waterf UIg Landh Otheri On-sitej Off-sitek On- and off-site 

AR 1 54 No data 0 0 0 54 0 54 

CO 1 0 No data 0 0 0 0 0 0 

KY 1 122 0 0 0 0 122 0 122 

LA 8 1,986 5 0 35 0 1,991 35 2,026 

NY 1 0 No data 0 No data 0 No data 0 0 

OH 1 5 0 0 255 0 5 255 260 

SC 1 0 No data 0 0 0 0 0 0 

TX 6 1,003 1 0 18 0 1,022 0 1,022 

Total 20 3,170 6 0 308 0 3,194 290 3,484 

a

The TRI data should be used with caution since only certain types of facilities are required to report. This is not an 

exhaustive list. Data are rounded to nearest whole number.
 b

Data in TRI are maximum amounts released by each facility.
 c

Post office state abbreviations are used.
 d

Number of reporting facilities.

e

The sum of fugitive and point source releases are included in releases to air by a given facility.
 f

Surface water discharges, waste water treatment-(metals only), and publicly owned treatment works (POTWs) (metal
 

and metal compounds).

g

Class I wells, Class II-V wells, and underground injection. h

Resource Conservation and Recovery Act (RCRA) subtitle C landfills; other on-site landfills, land treatment, surface 

impoundments, other land disposal, other landfills.

i

Storage only, solidification/stabilization (metals only), other off-site management, transfers to waste broker for
 

disposal, unknown

j

The sum of all releases of the chemical to air, land, water, and underground injection wells. k

Total amount of chemical transferred off-site, including to POTWs.
 

RF = reporting facilities; UI = underground injection 

Source: TRI05 2007 (Data are from 2005) 
 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 124 

6. POTENTIAL FOR HUMAN EXPOSURE 

with each chemical being represented according to its fraction in the stack of the incinerator. Annual 

stack emissions of 1,1,2,2-tetrachloroethane from such an incinerator were estimated to be 7.1 kg, 

assuming a standard destruction and removal efficiency of 99.99% and a waste throughput of 

2.76x107 kg/year. Current information on incinerator-related generation of 1,1,2,2-tetrachloroethane 

could not be identified. Tam and Neumann (2004) reported that 607 pounds of 1,1,2,2-tetrachloroethane 

were emitted into the air in Portland, Oregon during 1996. 

1,1,2,2-Tetrachloroethane has been identified in air samples collected at 20 of the 1,699 NPL hazardous 

waste sites where it was detected in some environmental media (HazDat 2008). 

6.2.2 Water 

Estimated releases of 6 pounds (0.002 metric tons) of 1,1,2,2-tetrachloroethane to surface water from 

20 domestic manufacturing and processing facilities in 2005, accounted for <1% of the estimated total 

environmental releases from facilities required to report to the TRI (TRI05 2007). These releases are 

summarized in Table 6-1. 

1,1,2,2-Tetrachloroethane may be released into water through effluent from manufacturing facilities that 

use this substance as a chemical intermediate. Though no longer representing current conditions, a 

comprehensive waste water survey conducted by the Effluent Guidelines Division of the EPA 

(Shackelford et al. 1983) documented that 1,1,2,2-tetrachloroethane has been detected in a variety of 

waste water discharges. Approximately 4,000 samples of waste water from a broad range of industrial 

facilities and publicly owned treatment works (POTWs) were analyzed in this survey. 

1,1,2,2-Tetrachloroethane has been identified in groundwater and surface water samples collected at 

218 and 43 of the 1,699 NPL hazardous waste sites, respectively, where it was detected in some 

environmental media (HazDat 2008). 

6.2.3 Soil 

Estimated releases of 308 pounds (0.1 metric tons) of 1,1,2,2-tetrachloroethane to soils from 20 domestic 

manufacturing and processing facilities in 2005, accounted for about 9% of the estimated total 
 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 125 

6. POTENTIAL FOR HUMAN EXPOSURE 

environmental releases from facilities required to report to the TRI (TRI05 2007). These releases are 

summarized in Table 6-1. 

1,1,2,2-Tetrachloroethane may be released to soil when it is disposed of in landfills. Another possible 

mode of release to soil is from accidental spills of products or wastes containing 1,1,2,2-tetrachloroethane 

during overland transportation. 

1,1,2,2-Tetrachloroethane has been identified in soil and sediment samples collected at 112 and 22 of the 

1,699 NPL hazardous waste sites, respectively, where it was detected in some environmental media 

(HazDat 2008). 

6.3 ENVIRONMENTAL FATE 

6.3.1 Transport and Partitioning 

Most of the 1,1,2,2-tetrachloroethane that is released to the environment enters the atmosphere, where it is 

expected to be degraded by reaction with photochemically produced hydroxyl radicals. The half-life for 

this reaction is approximately 54 days based on a measured rate constant of 2.50x10-13 cm3

/moleculesecond (Tosato et al. 1991). 1,1,2,2-Tetrachloroethane that is not degraded in the troposphere may be 

transported to the stratosphere by processes such as diffusion, where it will then photodegrade rapidly. 

However, based on an estimated half-life and a tropospheric-to-stratospheric turnover time of 30 years 

(EPA 1979), it has been predicted that <1% of tropospheric 1,1,2,2-tetrachloroethane would eventually 

reach the stratosphere. Removal of 1,1,2,2-tetrachloroethane from the atmosphere may also occur 

through washout by precipitation; however, most 1,1,2,2-tetrachloroethane removed by this mechanism 

will likely reenter the atmosphere by volatilization. 

1,1,2,2-Tetrachloroethane that is released into surface water will be lost by volatilization in a period of 

days to weeks. Based on a measured Henry's law constant of 3.67x10-4 atm-m3

/mol (Leighton and Calo 

1981), the volatilization half-life of 1,1,2,2-tetrachloroethane (assuming first-order decay kinetics) is 

estimated to be 6.9 hours from a model river 1 m deep flowing 1 m/second with a wind of 3 m/second and 

6.1 days from a model lake 1 m deep flowing 0.05 m/second with a wind of 0.5 m/second (Thomas 1990). 

In waste water treatment plants that receive volatile compounds such as 1,1,2,2-tetrachloroethane from 

industrial discharges or other sources, air stripping is an important mechanism for transferring the 

chemical from the water into the air. Air stripping technologies involve cascading waste waters over 
 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 126 

6. POTENTIAL FOR HUMAN EXPOSURE 

trickling towers, the use of spray devices to convert the fluids into droplets or aerosols, and other 

techniques to increase the ordinary volatilization processes across liquid surfaces. In stripping, as 

opposed to ordinary volatilization, the liquid and gas phases are dispersed. As a result, the interfacial 

surface area is much greater and liquid/gas mass transfer is greatly enhanced. Stripping, not 

biodegradation, was found to be responsible for removing 96% of the 1,1,2,2-tetrachloroethane in tests 

performed with activated sludge reactors (Kincannon et al. 1983). The half-disappearance time for 

1,1,2,2-tetrachloroethane removal by stripping was 0.3 hours. In view of its moderate vapor pressure and 

low adsorptivity to soil, 1,1,2,2-tetrachloroethane would be expected to readily volatilize from soil 

surfaces. However, 1,1,2,2-tetrachloroethane may also leach into groundwater as indicated by its 

presence in aquifer discharge (Lorah and Voytek 2004). 

The Koc of 1,1,2,2-tetrachloroethane is 46 in a silt loam soil (Chiou et al. 1979). Valsaraj et al. (1999) 

reported Koc values of 240, 216, and 173 for 1,1,2,2-tetrachloroethane in sandy soil (0.11% organic 

carbon), clay soil (0.25% organic carbon), and silty clay soil (1.13% organic carbon), respectively. Koc 

values of 118 and 83 have also been reported (Borisover and Graber 1997; Chu and Chan 2000). These 

Koc values suggests that 1,1,2,2-tetrachloroethane will not adsorb appreciably to soil, suspended solids, 

and sediment (Swann et al. 1983). 

The bioconcentration factor (BCF) of 1,1,2,2-tetrachloroethane measured in bluegill sunfish was 8 in a 

14-day experiment (Barrows et al. 1980). A bioconcentration factor of 2 for 1,1,2,2-tetrachloroethane in 

fathead minnows has also been reported (ASTER 1995). According to a classification scheme, these BCF 

values suggest that the potential for bioconcentration of 1,1,2,2-tetrachloroethane in aquatic organisms is 

low (Franke et al. 1994). 

6.3.2 Transformation and Degradation 

6.3.2.1 Air 

The primary reaction of 1,1,2,2-tetrachloroethane in the atmosphere is expected to be with photochemically produced hydroxyl radicals. Based on a measured rate constant of 2.50x10-13 cm3

/moleculeseconds at 25 °C and a hydroxyl radical concentration of 5.00x105 molecules/cm3

, the half-life for this 

reaction is 64 days (Tosato et al. 1991). 1,1,2,2-Tetrachloroethane that reaches the stratosphere is 

expected to be photolyzed by the shorter wavelength ultraviolet light present at these altitudes to produce 

chlorine radicals (EPA 1979; Spence and Hanst 1978). These chlorine radicals can destroy ozone 
 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 127 

6. POTENTIAL FOR HUMAN EXPOSURE 

molecules found in the stratosphere. However, since <1% of tropospheric 1,1,2,2-tetrachloroethane is 

expected to reach the stratosphere, release of this chemical into the atmosphere is not expected to 

contribute significantly to the depletion of the ozone layer (EPA 1979; WHO 1998). 

6.3.2.2 Water 

1,1,2,2-Tetrachloroethane undergoes base-catalyzed hydrolysis in water at environmental pH to form 

trichloroethylene (Cervini-Silva 2003; Cooper et al. 1987; Haag and Mill 1988). Investigators have 

measured the hydrolysis rate over a range of pHs. A second-order hydrolysis half-life of 102 days at 

25 °C and pH 7.0 has been reported (Cooper et al. 1987). In solutions of a much lower ionic strength 

more typical of groundwater, empirical half-disappearance times of 573 days at pH 6.05 and 36 days at 

pH 7.01 were obtained for 1,1,2,2-tetrachloroethane (Haag and Mill 1988). Similarly, researchers at Dow 

Chemical Company found that at ppm concentrations, 1,1,2,2-tetrachloroethane undergoes abiotic 

transformation to trichloroethylene in a sterile, anaerobic solution at pH 7.0 (Klečka and Gonsior 1983). 

After 28 days, 25% of the chemical had degraded. Hydrolysis of 1,1,2,2-tetrachloroethane was not 

affected by contact with the low-carbon aquifer materials associated with groundwater. 1,1,2,2-Tetrachloroethane in pore-water extracted from sediments showed a 29.1-day half-life at pH values between 

7.0 and 7.5 (Haag and Mill 1988). In an anoxic sediment-water system (pH unreported) the half-life of 

1,1,2,2-tetrachloroethane was 6.6 days (Jafvert and Wolfe 1987). Chemical hydrolysis and 

biodegradation were competing processes. 1,1,2,2-Tetrachloroethane (8.4 mg/L) was degraded by 100% 

after 4 days in anaerobic cell free extract with a reducing agent included and by approximately 35% after 

13 days in this extract without a reducing agent (Chen et al. 1996). 

Lorah and Olsen (1999a, 1999b) reported that 1,1,2,2-tetrachloroethane (300 μg/L) in groundwater from a

contaminated aquifer was anaerobically degraded to levels below detection within a 1.0 m vertical 

distance in the upward discharge through wetland sediment under increasingly reducing conditions. 

1,1,2,2-Tetrachloroethane (approximately 200 μg/L) was completely degraded 16 days after it was added 

to a wetland sediment and groundwater microcosm under methanogenic conditions. In contrast, only 

60% of 1,1,2,2-tetrachloroethane added to a sterile microcosm was degraded after 34 days, which 

indicates that both biotic and abiotic processes contributed to the degradation of this substance in these 

microcosms. The metabolites trichloroethylene, 1,2-dichloroethylene, 1,1,2-trichloroethane, 1,2-dichloroethane, and vinyl chloride were also degraded to below detectable levels within the 1.0 m vertical distance 

during the field study and within 34 days after addition of 1,1,2,2-tetrachloroethane during the microcosm 

tests (Lorah and Olsen 1999a, 1999b; Lorah and Voytek 2004). Further environmental fate and transport 
 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 128 

6. POTENTIAL FOR HUMAN EXPOSURE 

information for these degradation products can be found in their separate ATSDR profiles, which are 

available through the internet (http://www.atsdr.cdc.gov/toxpro2.html). The anaerobic biodegradation of 

1,1,2,2-tetrachloroethane can proceed through hydrogenolysis, dichloroelimination, or dehydrochlorination (Chen et al. 1996; Ferguson and Pietari 2000; Lorah and Olsen 1999b). Probable anaerobic 

degradation pathways for 1,1,2,2-tetrachloroethane are shown in Figure 6-2. 

Results of aerobic biodegradability tests are conflicting. One study, in which 5 and 10 ppm of the 

chemical were incubated with sewage seed for 7 days, followed by 3 successive 7-day subcultures, found 

no significant degradation under aerobic conditions (Tabak et al. 1981). Other investigators reported that 

1,1,2,2-tetrachloroethane (4.4 ppm) was degraded by 41% after 24 days in an unacclimated 

biodegradability test while no degradation of this substance (0.85 ppm) occurred after 5 days in a test 

using an acclimated seed (Mudder and Musterman 1982). A 19% loss of 1,1,2,2-tetrachloroethane (initial 

concentration 17.3 ppm) was obtained in a 5-day river die-away test using an acclimated system. None of 

the other chlorinated ethanes and ethenes in the study were found to be biodegradable. Many researchers, 

however, would attribute most losses involved with sewage treatment to air-stripping processes and not 

biodegradation (Kincannon et al. 1983). 

6.3.2.3 Sediment and Soil 

Based on limited information identified in the literature, both hydrolysis and anaerobic biodegradation 

appear to be significant transformation processes in soils and sediments. 

In a study of the transformation of various chlorinated ethenes and ethanes under conditions simulating 

soil conditions of landfills, 1,1,2,2-tetrachloroethane was transformed into such products as 1,1,2-trichloroethane, trichloroethene, cis-1,2-dichloroethene, trans-1,2-dichloroethene, 1,1-dichloroethene, and 

vinyl chloride. Samples were incubated for six weeks under anaerobic conditions after inoculation with a 

microorganism culture obtained from the anaerobic digester of a municipal waste water treatment facility 

(Hallen et al. 1986). These transformations were attributed in large measure to the anaerobic 

microorganisms. In another study, the transformation of 1,1,2,2-tetrachloroethane in sterilized, sedimentextracted pore water was investigated (Haag and Mill 1988). After a 6-day period, approximately 34% of 

the original 1,1,2,2-tetrachloroethane had been transformed at pH 6.05 and a temperature of 25 °C; at the 

same temperature and a pH of 7.01, 74% of the 1,1,2,2-tetrachloroethane was converted. In this 

experiment, the transformation was attributed primarily to hydrolysis. There was little observed sorption 

of 1,1,2,2-tetrachloroethane to the sediment, a low-carbon sandy material. 
 

 

1,1,2,2-TETRACHLOROETHANE 129 

6. POTENTIAL FOR HUMAN EXPOSURE 

Figure 6-2. Anaerobic Degradation Pathways for 1,1,2,2-Tetrachloroethane 

H H abiotic H Cl
 

Cl C C Cl
 C C
 

Cl Cl Cl Cl
 

1,1,2,2-tetrachloroethane 

H H 

trichloroethylene 

H H H Cl H Cl 
 

C C C C
 C C H C C Cl 

Cl Cl Cl H H Cl 

Cl Cl 

cis-1,2- trans-1,2- 1,1­

dichloroethylene dichloroethylene dichloroethylene 

H H
 H H
 

1,1,2-trichloroethane 

H C C H C C
 

Cl Cl
 H Cl
 

1,2-dichloroethane
 vinyl chloride 

H H H H 

H C C H C C 

Cl H H H

ethylene chloroethane 

H H
 

H C C H
 

H H
 

ethane
 

Hydrogenolysis 

Dichloroelimination 

Dehydrochlorination 

Source: adapted from Lorah and Olsen 1999b 
 

 

 

 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 130 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT 

Reliable evaluation of the potential for human exposure to 1,1,2,2-tetrachloroethane depends in part on 

the reliability of supporting analytical data from environmental samples and biological specimens. 

Concentrations of 1,1,2,2-tetrachloroethane 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 1,1,2,2-tetrachloroethane 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 1,1,2,2-tetrachloroethane in a variety of environmental media 

are detailed in Chapter 7. 

6.4.1 Air 

Background levels of 1,1,2,2-tetrachloroethane measured in the troposphere have ranged from ≤0.1 to 

0.4 ppt (Class and Ballschmiter 1986). Two air samples from rural areas of the United States did not 

contain detectable levels of the chemical (Brodzinsky and Singh 1982). In data collected in the late 1970s 

to early 1980s at 853 urban/suburban sites in the United States, the median sample concentration of 

1,1,2,2-tetrachloroethane was 5.4 ppt, with values ranging from less than detection limits to a maximum 

of 4,800 ppt (Brodzinsky and Singh 1982). More information has subsequently been added to this 

database, bringing the sample size for 1,1,2,2-tetrachloroethane to 1,011 monitoring records (EPA 1988c). 

With the addition of the new data, the overall median was computationally at or below the database lower 

detection limit value of zero; 75% of the samples showed concentrations ≤8 ppt. 1,1,2,2-Tetrachloroethane was found infrequently in the air of New Jersey cities; it was found in 9 of 38 samples in Newark, 

1 of 37 samples in Elizabeth, and 4 of 35 samples in Camden in the summer of 1981 (Harkov et al. 1983), 

and in 4 out of 105 samples from the same 3 cities in the winter of 1982 (Harkov et al. 1987). 

1,1,2,2-Tetrachloroethane concentrations were <1 ppbV in urban air samples from 13 sites located in 

Louisiana, Texas, Vermont, and New Jersey collected from September, 1996 to August, 1997 (Mohamed 

et al. 2002). 1,1,2,2-Tetrachloroethane was detected above 0.07 μg/m3 (9.8 ppt) in 609 out of 2,507 air 

samples collected from 25 sites across the state of Minnesota over a period of 8 years (1991–1998) (Pratt 

et al. 2000). The mean, median, and maximum concentrations were 0.06, 0.03, and 6.87 μg/m3 (8.4, 4.2, 

and 962 ppt), respectively. Mean concentrations of 1,1,2,2-tetrachloroethane in major U.S. cities listed in 
 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 131 

6. POTENTIAL FOR HUMAN EXPOSURE 

other reports ranged from trace levels below detection limits to 57 ppb (Harkov et al. 1981, 1983; Lioy et 

al. 1985; Singh et al. 1981, 1982; Spicer et al. 1996). 

The only data on indoor levels of 1,1,2,2-tetrachloroethane were contained in a study of eight homes in 

Knoxville, Tennessee, obtained during the winter (Gupta et al. 1984). Ten of 16 samples (detection limits 

were not reported) contained 1,1,2,2-tetrachloroethane, with a mean concentration of 13.0 μg/m3 

(1.8 ppb). Although the source of the chemical was not investigated, the contamination might be 

attributed to consumer products used in the home or to outgassing of the chemical from construction 

material or household furnishings. 

An EPA study of the indoor-air pollution potential associated with 1,159 common household products 

(Sack et al. 1992) included 1,1,2,2-tetrachloroethane as one of 31 volatile organic compounds selected for 

analysis. 1,1,2,2-Tetrachloroethane was found in 216 of these products. It was especially common, in 

trace amounts, in adhesives, oils, greases, and lubricants. Concentrations in the products were uniformly 

near detection limits (detection limits not reported). Although trace amounts were present in a wide 

variety of products, Sack et al. (1992) concluded that 1,1,2,2-tetrachloroethane has a low potential to pose 

unacceptable human exposure risks in indoor air. 

The ranges of mean and maximum air concentrations of 1,1,2,2-tetrachloroethane in air at five NPL 

hazardous waste sites in New Jersey were 0.01–0.59 and 0.17–11.38 ppb, respectively, while the 

corresponding values for an urban landfill receiving municipal waste and nonhazardous industrial waste 

were 0.01 and 0.19 ppb (LaRegina et al. 1986). Samples of air surrounding the Kin-Buc waste disposal 

site near Edison, New Jersey contained up to 2.1 ppb of 1,1,2,2-tetrachloroethane. Air concentrations of 

0.226 ppb of 1,1,2,2-tetrachloroethane were found in Iberville Parish, Louisiana along the Mississippi 

River, where many organic chemical production and storage facilities are located (Pellizzari 1982). 

1,1,2,2-Tetrachloroethane was detected in air samples collected over the western Pacific Ocean between 

43 and 4 °N; however, concentrations were not specified (Quack and Suess 1999). 

6.4.2 Water 

Representative samples of surface water from New Jersey were analyzed during 1977–1979 (Page 1981). 

These samples were collected from urban, suburban, and rural areas showing every type of land use 

common in the state. Sixty-seven of the 608 surface water samples (11%) contained 1,1,2,2-tetrachloro-
 

 

 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 132 

6. POTENTIAL FOR HUMAN EXPOSURE 

ethane in concentrations as high as 3.0 ppb. Concentrations of 1,1,2,2-tetrachloroethane in U.S. surface 

waters reported in several studies range up to 9 ppb (EPA 1977, 1980; Konasewich et al. 1978; Ohio 

River Valley Sanitation Commission 1980; Page 1981). According to 1999–2006 nationwide U.S 

monitoring data from the STORET database, 1,1,2,2-tetrachloroethane was detected in 5,343 out of 

12,476 water samples (includes surface water and groundwater); however, only 391 of these detections 

were above the quantitation limit (unspecified). The mean, median, and range of quantifiable 

concentrations were 0.6, 0.5, and 0.1–25 μg/L (ppb), respectively (EPA 2006f). 

Representative samples of groundwater from New Jersey were also analyzed during 1977–1979 in a 

project summarized in Page (1981). Sixty-four of the 1,072 groundwater samples (6%) contained 

1,1,2,2-tetrachloroethane, with concentrations as high as 2.7 ppb. An example of groundwater pollution 

by an industrial source is the case of an abandoned organic chemical manufacturing facility in Salem, 

Ohio that operated from 1961 to 1973 (Khourey et al. 1984). Maximum concentrations of 1,1,2,2-tetrachloroethane were 0.501–43.0 ppm in five on-site monitoring wells and 0.556 ppm in an off-site private 

well. 1,1,2,2-Tetrachloroethane was detected in 5 out of 15 groundwater wells located at a landfill in 

Niagara Falls, New York that was contaminated with chlorinated solvents (Lee et al. 1995). 

1,1,2,2-Tetrachloroethane concentrations in these wells were 1.3, 250, 14, 1.6, and 1.1 ppm. The 

concentration of 1,1,2,2-tetrachloroethane during 4 bimonthly analyses of a surficial aquifer at Beach 

Point which is located in the Edgewood Area of the U.S. Army Garrison, Aberdeen Proving Ground, 

Maryland ranged from 9,000 to 17,000 μg/L (ppb) (Burton et al. 2002). The water from the aquifer

discharges into the Bush River, a tributary of the Chesapeake Bay. The concentration of 1,1,2,2-tetrachloroethane were below the detection limit of 0.09 μg/L (ppb) in 30 randomly distributed monitoring 

wells located in Wichita, Kansas during the High Plains Regional Ground-Water Study conducted in 2000 

as part of the U.S. Geological Survey’s National Water Quality Assessment Program (USGS 2002). The 

concentration of 1,1,2,2-tetrachloroethane was below 0.13 μg/L (ppb) in 34 wells (including 5 public use 

wells) in Cook Inlet Basin, Alaska sampled during 1999 (USGS 2001). 

In the only study of rainwater located in the literature, 1,1,2,2-tetrachloroethane was not found in nine 

rain events in Portland, Oregon, during the spring and fall of 1982 (Pankow et al. 1984). 

There is limited information on the occurrence of 1,1,2,2-tetrachloroethane in ambient surface water or 

groundwater used as drinking water supplies for community water supply systems. A study of 

30 Canadian public water treatment facilities did not show levels of 1,1,2,2-tetrachloroethane above a 

1 ppb detection limit (Otson et al. 1982). In a United States Groundwater Supply survey, none of the 
 

 

 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 133 

6. POTENTIAL FOR HUMAN EXPOSURE 

945 water supplies derived from tested groundwater sources contained 1,1,2,2-tetrachloroethane at the 

sensitivity limit of 0.5 ppb (Westrick et al. 1984). It was detected in 1 of 13 drinking water wells in 

Tacoma, Washington (Shilling 1985). It was not found in any of the 1,174 community wells and 

617 private wells in a Wisconsin survey conducted in the early 1980s (Krill and Sonzogni 1986). 

According to Round 2 data (1993–1997) reported under the EPA Unregulated Contaminant Monitoring 

Program (UCM), 1,1,2,2-tetrachloroethane was detected in 81 out of 166,599 samples collected from 

public water systems across the United States with a mean concentration of 5.0 ppb and a range of 0.05– 

200.00 ppb (EPA 2001b). 

6.4.3 Sediment and Soil 

Limited information was located on general background levels of 1,1,2,2-tetrachloroethane in soils and 

sediments, with most studies focusing on problems associated with the remediation of waste sites. In an 

analysis of test wells around RCRA disposal sites, 1,1,2,2-tetrachloroethane was documented at levels 

above detection limits at 25 of 479 sites from a national sample (Plumb 1991). At one waste disposal site 

in Pennsylvania (Sabel and Clark 1984), the concentration of 1,1,2,2-tetrachloroethane in a soil sample 

was 2.4 ppm. Reported concentrations of 1,1,2,2-tetrachloroethane in sediment collected from the 

Calcasieu River estuary in Louisiana ranged from 0 to 13.0 mg/kg (Redmond et al. 1996). According to 

1999–2006 nationwide U.S. monitoring data from the STORET database, 1,1,2,2-tetrachloroethane was 

detected in 6 out of 635 soil samples. The mean, median, and range of 1,1,2,2-tetrachloroethane 

concentrations in the six samples were 0.06, 0.02, and 0.0012–0.21 mg/kg, respectively (EPA 2006f). 

According to STORET data, 1,1,2,2-tetrachloroethane was detected in 142 out of 335 sediment samples; 

however, only 3 of these detections were above the quantitation limit (unspecified). Concentrations in the 

three samples were 160, 130, and 180 μg/kg.

6.4.4 Other Environmental Media 

The data on 1,1,2,2-tetrachloroethane in fish or other biotic tissue samples are very limited. Examination 

of EPA’s Fish Consumption Advisory Database (EPA 1995) showed an advisory in effect for all species 

of fish on the lower Ashtabula River. Such fish consumption advisories are issued by states if there is 

some concern over the management of risks from the public eating fish caught in rivers and other water 

bodies. While the pollution issues in the Ashtabula River have led to cautionary warnings in the 

consumption of locally caught fishes, available information on bioconcentration factors summarized in 
 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 134 

6. POTENTIAL FOR HUMAN EXPOSURE 

Section 6.3.1 above does not suggest a tendency for 1,1,2,2-tetrachloroethane to bioconcentrate, 

biomagnify, or bioaccumulate in the tissues of fish or shellfish. 

1,1,2,2-Tetrachloroethane was analyzed for but not detected in approximately 90 foods during the U.S. 

Food and Drug Administration’s Total Diet Study (TDS) (FDA 2005b). During a study of organic 

compounds in tobacco smoke, the concentrations of 1,1,2,2-tetrachloroethane in ultra low tar, full flavor 

low tar, and full flavor cigarette brands were 6.00, 3.78, and 3.19 μg/cigarette, respectively (Bi et al. 

2005). 

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE 

Exposure of the general population to 1,1,2,2-tetrachloroethane is expected to be very low based on the 

low concentrations reported for this substance in environmental media and the fact that it is no longer 

used as an end product. Individuals located near hazardous waste sites and facilities where this substance 

is used as a chemical intermediate may be exposed to 1,1,2,2-tetrachloroethane via inhalation of 

contaminated air, ingestion of contaminated drinking water, or dermal contact with contaminated soil. 

Exposures are also possible in areas around incinerators or cement kilns. Modeling estimates were made 

of 1,1,2,2-tetrachloroethane exposure due to inhalation and ingestion of contamination produced by 

incinerating chlorinated solvent waste at incinerator facilities at sites in southern California, the central 

Midwest, and the northern Midwest (Travis et al. 1986). For the California site, the average individual 

inhalation and ingestion intake was 774 and 285 μg/year, respectively. While food intake accounted for

27% of the total individual dose at the California site, this contribution was 60 and 65% for the two 

Midwestern sites. 

A National Occupational Exposure Survey (NOES) conducted by NIOSH from 1981 to 1983 estimated 

that 4,145 workers are potentially exposed to 1,1,2,2-tetrachloroethane in the United States (NIOSH 

2006). Of these estimated exposures, 3,666 were in occupations involving work in chemical research and 

development laboratories with the other exposures involving jobs in industrial chemical plants. The 

estimate is provisional since all the data for trade name products which may contain 1,1,2,2-tetrachloroethane have not been analyzed. The NOES study was based on field surveys of 4,490 facilities and was 

designed as a nationwide survey based on a statistical sample of virtually all workplace environments in 

the United States where 8 or more persons are employed (based on all Standard Industrial Classification 

(SIC) code workplace types except mining and agriculture) (Sieber et al. 1991). The NOES database does 
 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 135 

6. POTENTIAL FOR HUMAN EXPOSURE 

not contain information on the frequency, concentration, or duration of exposure; the survey provides 

only estimates of workers potentially exposed to chemicals in the workplace. 

According to OSHA (1991), the current 8-hour TWA permissible exposure level for 1,1,2,2-tetrachloroethane is 1 ppm. According to NIOSH (1992), the recommended exposure level for a 10-hour TWA is 

1 ppm (7 mg/m3

) 1,1,2,2-tetrachloroethane. 

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). 

Data regarding the exposure of children to 1,1,2,2-tetrachloroethane (including body burden data, 

detection in breast milk, dietary exposure data, pathways of exposure, differences in intake compared to 

adults, and secondary exposure data) are not available in the literature. However, based on human breast 

milk/blood partition coefficients of 2.26-3.55 calculated for other chlorinated alkanes (Fisher et al. 1997), 

it is assumed that 1,1,2,2-tetrachloroethane would readily partition to breast milk. Children who live near 

areas where 1,1,2,2-tetrachloroethane is released may be exposed by breathing contaminated air, by 

touching or eating contaminated soil, or by contact with or drinking contaminated water. 

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES 

Exposures are possible for individuals living near waste disposal facilities where 1,1,2,2-tetrachloroethane 

site contamination has occurred. Higher exposures may occur for workers at facilities where 
 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 136 

6. POTENTIAL FOR HUMAN EXPOSURE 

1,1,2,2-tetrachloroethane is still used as a chemical intermediate. Other populations with higher 

exposures would include people living close to NPL or other waste sites where leachates or runoff from 

contaminated soils could affect groundwater used for drinking water. In at least one instance, pollution 

from a large NPL site in Ohio has resulted in a fish consumption advisory for local recreational and 

subsistence fishers. Higher concentrations of 1,1,2,2-tetrachloroethane have been found in groundwater 

at a few locations in the United States. Individuals who use or drink the groundwater from these locations 

may have higher exposures to 1,1,2,2-tetrachloroethane. 

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 1,1,2,2-tetrachloroethane 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 1,1,2,2-tetrachloroethane. 

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. The physical and chemical properties of 1,1,2,2-tetrachloroethane are well characterized and allow prediction of the environmental fate of the compound (see 

Table 4-2). No additional studies are required at this time. 

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 
 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 137 

6. POTENTIAL FOR HUMAN EXPOSURE 

information for 2004, became available in May of 2006. This database is updated yearly and should 

provide a list of industrial production facilities and emissions. 

Production methods and uses for 1,1,2,2-tetrachloroethane are documented (Archer 1979; IARC 1979), 

but there is no recent detailed breakdown of the percentage of production consumed by each use category. 

Figures on current exports are also lacking. Approximately 440 million pounds (199 million kg) of 

1,1,2,2-tetrachloroethane were produced in the United States in 1967 (Konietzko 1984). Production 

declined markedly thereafter, falling to an estimated 34 million pounds (15 million kg) by 1974. While 

1,1,2,2-tetrachloroethane is apparently no longer produced as a final product, it may occur as a chemical 

intermediate or waste product in the manufacture of other chemicals (CEPA 1993). Better quantitative 

measures of current production, including production for export, is a data need for estimating the potential 

for environmental releases from various industries, as well as potential concentrations in the environment. 

Knowledge of which consumer products contain 1,1,2,2-tetrachloroethane is also a data need for 

estimating general population exposure. Unfortunately, this type of detailed information is difficult to 

obtain since companies consider it to be confidential information. While monitoring information on 

discharges was gathered during the 1970s and early 1980s when the EPA was developing criteria and 

effluent guidelines for a number of priority pollutant toxics (Shackelford et al. 1983), the TRI now 

constitutes the only major broad-based survey of releases to the environment. According to the most 

recent TRI information (TRI04 2006), releases to the air and water still continue from processing facilities 

in the United States. At present, the TRI data only cover major industrial sectors, so some releases may 

go unreported. Possible expansions of the types of facilities required to submit information under the TRI 

reporting requirements could help make this source of information more comprehensive. 

While regulatory coverage for halogenated organic wastes has become increasingly more well defined 

(EPA 1989), record keeping under RCRA procedures works best when a chemical is a major constituent 

in a waste. Since 1,1,2,2-tetrachloroethane is now usually a minor component in other waste materials, 

there is often little documentation of the amounts of 1,1,2,2-tetrachloroethane entering waste disposal 

sites. 

Environmental Fate. Half-lives and degradation rates for the atmospheric photooxidation, aqueous 

hydrolysis, and biodegradation of 1,1,2,2-tetrachloroethane are available. 1,1,2,2-Tetrachloroethane is 

quite volatile, but the highest potential for persistent pollution is when the chemical has been introduced 

into sediments and groundwater (Atkinson 1987; HSDB 1996; Mackay and Shiu 1981). While the 

chemical can be biodegraded under anaerobic conditions (Bouwer and McCarty 1983), there are major 
 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 138 

6. POTENTIAL FOR HUMAN EXPOSURE 

differences under aerobic conditions (Tabak et al. 1981). Further investigation would be helpful to 

resolve the discrepancies in the aerobic degradation data for 1,1,2,2-tetrachloroethane and would rank as a 

major data need. 

Bioavailability from Environmental Media. Based on available animal studies (Mitoma et al. 

1985; Morgan et al. 1970; Yllner 1971) and inferences from studies of similar low molecular weight 

chlorinated alkanes in humans, inhalation, ingestion, and dermal exposure are the major routes of 

exposure (Pellizzari et al. 1982). 1,1,2,2-Tetrachloroethane in air and/or water can be expected to be 

absorbed readily into the systemic circulation, and 1,1,2,2-tetrachloroethane in soil may be absorbed to 

some extent through the skin. Analyses of 1,1,2,2-tetrachloroethane and its stable metabolites in body 

fluids and tissues of people exposed to the chemical is a data need to improve the knowledge base on the 

bioavailability of 1,1,2,2-tetrachloroethane. 

Food Chain Bioaccumulation. Given its tendency to either volatilize to the atmosphere (Atkinson 

1987; Mackay and Shiu 1981) or become transformed into such other chemicals as TCE (Cooper et al. 

1987; Haag and Mill 1988), 1,1,2,2-tetrachloroethane shows little potential for bioaccumulation. Based 

on measured bioconcentration factors (ASTER 1995; Barrows et al. 1980), 1,1,2,2-tetrachloroethane is 

not expected to bioconcentrate and is not considered to show significant potential to bioaccumulate in 

food chains. No major data needs are apparent for this information category. 

Exposure Levels in Environmental Media. Reliable monitoring data for the levels of 

1,1,2,2-tetrachloroethane in contaminated media at hazardous waste sites are needed so that the 

information obtained on levels of 1,1,2,2-tetrachloroethane in the environment can be used in 

combination with the known body burden of 1,1,2,2-tetrachloroethane to assess the potential risk of 

adverse health effects in populations living in the vicinity of hazardous waste sites. 

In studies based on monitoring data from the late 1970s and early 1980s, 1,1,2,2-tetrachloroethane 

concentrations in receiving waters (primarily rivers) of at least 10 ppb were documented in approximately 

10% of the samples collected in a national study of runoff from urban areas, with a maximum reported 

concentration of 1,400 ppb (Cole et al. 1984). In soils and sediments, information from NPL sites shows 

detections at 112 and 22 of 1,699 sites, respectively. Since the treatment, storage, and distribution 

processes used in large community drinking water systems will generally release volatile chemicals to the 

air, 1,1,2,2-tetrachloroethane concentrations in public drinking water are generally very low. The 

chemical has been detected in untreated groundwater formations used for private wells in some parts of 
 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 139 

6. POTENTIAL FOR HUMAN EXPOSURE 

New Jersey (Page 1981). The highest levels have been found in groundwater in the vicinity of waste 

disposal sites (Khourey et al. 1984). Background levels of 1,1,2,2-tetrachloroethane in the air are 

typically <0.4 ppt (Brodzinsky and Singh 1982; Class and Ballschmiter 1986). Limited data collected in 

the vicinity of waste disposal sites has shown ambient air levels considerably higher (from >1 ppb to as 

high as 2.1 ppb) (Gupta et al. 1984; LaRegina et al. 1986). 

Although commercial use of this substance appears to have ceased, it is still produced and used in large 

amounts as a chemical intermediate; therefore, the potential exists for this substance to be released in 

large amounts into the environment. More recent data concerning the levels of this chemical in the 

atmosphere as well as in soils, sediment, groundwater, and surface water are needed for determining 

current background concentrations and exposure levels. Reliable monitoring data for the levels of 

1,1,2,2-tetrachloroethane in contaminated media at hazardous waste sites are needed, so that the 

information obtained on levels of 1,1,2,2-tetrachloroethane in the environment can be used in 

combination with the known body burdens of 1,1,2,2-tetrachloroethane to assess bioavailability and 

potential risks of adverse health effects in populations living in the vicinity of hazardous waste sites. 

Monitoring of 1,1,2,2-tetrachloroethane levels in the air of homes and buildings located near areas where 

this substance is released would be helpful. Although 1,1,2,2-tetrachloroethane does not appear to be 

present in food, additional information would be helpful in verifying this. Monitoring data on the 

concentrations of this substance in plants and animals in the environment are needed. 

Exposure Levels in Humans. Information on exposure levels in humans is extremely limited, with 

most conclusions on health effects being based on inferences from animal studies (Yllner 1971). General 

population and occupations exposure levels have been based on models (Travis et al. 1986) or provisional 

estimation techniques (NIOSH 2006). Improved information on human exposure levels is therefore a 

data need. Information on known populations with unusually high exposures to 1,1,2,2-tetrachloroethane 

would be helpful. 

This information is necessary for assessing the need to conduct health studies on these populations. 

Exposures of Children. Data regarding the exposure of children to 1,1,2,2-tetrachloroethane 

(including body burden data, detection in breast milk, dietary exposure data, pathways of exposure, 

differences in intake compared to adults, and secondary exposure data) are not available and would be 

helpful in satisfying this data need. In addition, means of decreasing exposure of children to this 

substance should be identified. 
 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 140 

6. POTENTIAL FOR HUMAN EXPOSURE 

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 1,1,2,2-tetrachloroethane were located. This 

substance is not currently one of the compounds for which a sub-registry has been established in the 

National Exposure Registry. The substance 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 this substance. 

6.8.2 Ongoing Studies 

No information was found to indicate that there are studies in progress that relate to the environmental 

fate of 1,1,2,2-tetrachloroethane (FEDRIP 2006). Similarly, no ongoing monitoring or exposure studies 

were identified. 
 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 141 

7. ANALYTICAL METHODS 

The purpose of this chapter is to describe the analytical methods that are available for detecting, 

measuring, and/or monitoring 1,1,2,2-tetrachloroethane, its metabolites, and other biomarkers of exposure 

and effect to 1,1,2,2-tetrachloroethane. 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. 

7.1 BIOLOGICAL MATERIALS 

A few studies were found in the literature that report the determination of this compound in biological 

matrices. The discussion about the method that may be most sensitive for the determination of 

tetrachloroethane levels in environmental samples and the advantages and disadvantages of the commonly 

used methods (see Section 7.2) are also applicable to biological samples. Because of its higher boiling 

point and the possibility of its loss through chemical reactions (Yasuda and Loughran 1977), the recovery 

of this compound from complex biological samples by most analytical methods is expected to be lower 

than the recoveries from air and water samples. The analytical methods for the determination of 

1,1,2,2-tetrachloroethane in biological matrices are given in Table 7-1. Information about methods for 

metabolites of 1,1,2,2-tetrachloroethane in animal samples is given in Section 7.3.1; these methods should 

be applicable to human samples. 

Chen et al. (1993) have reported a method for 1,1,2,2-tetrachloroethane in blood and several types of 

tissue from rats. Samples were homogenized with saline and isooctane, and an aliquot of the isooctane 

was transferred to a sampling vial for headspace/gas chromatography (GC) analysis. Fairly low detection 

limits (400 ng/g) and good recoveries (90–100%) were reported. Another method for volatile compounds 

in blood, urine, and tissues that should be applicable to the analysis of 1,1,2,2-tetrachloroethane was 

reported by Streete et al. (1992). In this case, headspace analysis was used to determine 1,1,2,2-tetrachloroethane in blood, urine, and tissue (after treatment with a proteolytic enzyme). The authors stress 
 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 142 

7. ANALYTICAL METHODS 

Table 7-1. Analytical Methods for Determining 1,1,2,2-Tetrachloroethane in 

Biological Materials
 

Sample 

matrix Preparation method 

Analytical 

method 

Sample 

detection 

limit 

Percent 

recovery Reference 

Exhaled 

air 

Collection of exhaled air through 

valved, Teflon spirometer in Tedlar 

bag; organics adsorbed onto Tenax 

as air is pulled through adsorbent; 

thermal desorption of Tenax 

Cryofocussing 

HRGC/MS 

No data No data Hartwell et al. 

1987 

Whole 

blood 

Analyte adsorbed onto Tenax during 

purge and trap; thermal desorption 

onto GC column 

GC/MS 500 ppt 

(500 ng/L) 

22–27 at 

1 ppb 

Cramer et al. 

1988 

Blood Purge and trap of 10 mL blood that 

was collected into specially prepared 

vacutainers; quantitation based on 

isotopically-labeled internal standards 

GC/HRMS 0.005 ppb 

(5 ng/L) 

116 at 

0.063 ppb to 

76 at 

0.41 ppb 

Ashley et al. 

1992 

Liver, 

brain, 

kidney, 

fat, heart, 

lung, 

muscle, 

blood 

Placement of tissue into chilled 20 mL 

glass vials containing 2 mL ice-cold 

saline and 8 mL isooctane; 

homogenization (3–20 s depending 

on tissue), vortexing and 

centrifugation; transferring 20 μL of 

isooctane to 8 mL headspace vial, 

equilibration for 10 minutes/100 °C 

and injection of aliquot of headspace 

into GC 

GC/ECD 400 ng/g 

(400 ppb) 

assuming 

1 g of tissue 

90–100 

(average % 

RSD=1.7%) 

depending 

on tissue 

Chen et al. 

1993 

Blood, 

urine, 

tissues, 

consumer 

products 

Blood/urine: Equilibration of sample 

with internal standard in 7 mL vial at 

65 °C for 15 minutes. Injection of 

0.1–0.3 mL of headspace into GC 

using gas tight syringe 

GC then 

split to both 

FID and 

ECD 

No data No data Streete et al. 

1992 

Blood, 

urine, 

tissues, 

Tissue: Placement of 20–50 mg wet 

mass (removed while it is frozen) into 

7 mL vial with internal standard and 

GC then 

split to both 

FID and 

No data No data Streete et al. 

1992 

consumer 

products 

1 mg Subtilisin A; equilibration and 

analysis as for blood 

ECD 

Blood, 

urine, 

tissues, 

Product: Analysis of headspace after 

placing small volume of product into 

vial 

GC then 

split to both 

FID and 

No data No data Streete et al. 

1992 

consumer ECD 

products 
 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 143 

7. ANALYTICAL METHODS 

Table 7-1. Analytical Methods for Determining 1,1,2,2-Tetrachloroethane in 

Biological Materials
 

Sample 

matrix Preparation method 

Analytical 

method 

Sample 

detection 

limit 

Percent 

recovery Reference 

Blood, 

urine 

Blood: 400 μL placed in a 4-mL vial 

fitted with a septum and placed on the 

heater for 30 minutes at 50 °C. The 

SPME then 

GC/MS 

0.5 μg/L No data Guidotti et al. 

2001 

septum was pierced with the SPME 

syringe needle and the fiber was 

exposed to the headspace for 

10 minutes. The fiber was then 

thermally desorbed for 1 minute. 

Blood, 

urine 

Urine: 2 mL placed in a 4-mL vial 

with a septum and placed on the 

heater for 30 minutes at 50 °C. The 

SPME then 

GC/MS 

4 ng/L No data Guidotti et al. 

2001 

septum was pierced with the SPME 

syringe needle and the fiber was 

exposed to the headspace for 

10 minutes. The fiber was then 

thermally desorbed for 1 minute. 

ECD = electron capture detector; FID = flame ionization detector; GC = gas chromatography; HRGC = high 

resolution gas chromatography; HRMS = high resolution mass spectrometry; MS = mass spectrometry; 

RSD = relative standard deviation; SPME = solid phase microextraction 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 144 

7. ANALYTICAL METHODS 

the importance of collecting liquid samples in a container with no headspace and keeping tissue samples 

frozen until a 20–50 mg piece is placed into the headspace-sampling vial. The most sensitive method 

found is based on purge and trap isotope dilution GC in conjunction with high resolution mass 

spectrometry (GC/HRMS). This method from the Centers for Disease Control and Prevention laboratory 

in Atlanta (Ashley et al. 1992) reported a limit of detection (LOD) for 1,1,2,2-tetrachloroethane in blood 

of 0.005 ppb with recoveries ranging from 116% at 0.063 ppb to 76% at 0.41 ppb. Great effort was 

devoted to the clean-up of collection and analysis equipment to make such LODs possible. Additional 

information about the mass spectrometric (MS) aspects of the method was reported by Bonin et al. 

(1992). Guidotti et al. (2001) describes a solid-phase microextraction (SPME) method that can be used to 

determine 1,1,2,2-tetrachloroethane in blood and urine. In this method, a fiber made of a fused silica 

support coated with the appropriate phase is exposed to sample headspace. After the appropriate amount 

of time has passed, the fiber is removed and thermally desorbed. Separation and detection of analytes is 

accomplished by GC-MS. 

7.2 ENVIRONMENTAL SAMPLES 

Methods for the analysis of 1,1,2,2-tetrachloroethane in environmental samples are presented in 

Table 7-2. There are two common methods used for the concentration of 1,1,2,2-tetrachloroethane from 

air. One is the direct collection of organics in a cryogenically cooled trap in line with a GC; the other 

method is concentration of the organic via adsorption on a sorbent column followed by thermal or solvent 

desorption. An advantage of the direct sampling approach is that it can be very simple. The 

disadvantages of the cryogenic cooling approach are that the method is cumbersome and that 

condensation of moisture from air may block the passage of further air flow through the trap. The 

sorbent-based concentration methods permit very large concentration factors and, as a result, good LODs. 

The disadvantages of sorbent tubes are that the sorption and desorption efficiencies may not be 100% 

(breakthrough during collection and poor recovery during analyte desorption) and that the background 

impurities in the sorbent tubes might elevate the method detection limit (Cox 1983). An additional 

problem with sorbent tubes is that analyte can be lost if the tube is improperly stored after sample 

collection. For example, Atlas and Schauffler (1991) reported losses for 1,1,2,2-tetrachloroethane of 50% 

when the charcoal sorbent tube was stored at room temperature for 2 days before desorption and analysis. 

The recoveries from the same type of tubes were very good when the tubes were stored frozen for up to 

30 days after sample collection. Chemical transformation of 1,1,2,2-tetrachloroethane to 

trichloroethylene has been reported (NIOSH 1994) on certain types of charcoal sorbents. It is also 

important to note that water introduced to the GC after both cryogenic and sorbent-based collection 
 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 145 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining 1,1,2,2-Tetrachloroethane in 

Environmental Materials
 

Sample 

matrix Preparation method 

Analytical 

method 

Sample 

detection limit 

Percent 

recovery Reference 

Air Sample preconcentration in liquid 

oxygen-cooled trap 

GC/ECD <1 ppt 

(<6.98 ng/m3) 

85 Singh et al. 

1981 

Breathing 

zone air 

Sample collection by 

adsorption onto Tenax 

followed by thermal 

desorption 

Cryofocussing 

HRGC-MS 

No data 80–120 Hartwell et al. 

1987; Krost et 

al. 1982; 

Air Sample adsorption 

onto Tenax followed by 

thermal desorption 

HRGC-ECD 0.1 ppt 

(0.698 ng/m3

) for 

1 L 

No data Class and 

Ballschmiter 

1987 

Air Preconcentration of 

analyte onto TenaxGC followed by 

thermal desorption 

onto GC column (EPA 

Method TO1) 

GC/MS No data No data EPA 1984b 

Air Collection of an aliquot 

of the air into a 

SUMMA passivated 

canister followed by 

pumping an aliquot of 

the air through a 

cryogenic trap to focus 

volatile organics; 

thermal desorption 

onto GC column (EPA 

Method TO14) 

GC/MS (full 

scan or 

selected ion 

monitoring); 

GC/FID/ECD/ 

PID 

No data; depends 

on air aliquot size 

and mode of 

detection 

No data; 

generally very 

good for nonpolar volatile 

organics 

EPA 1984c 

Air Preconcentration of 

analyte onto adsorbent 

trap containing 5 mg 

charcoal followed by 

immediate elution of 

GC/ECD Low parts per 

trillion in 20 L 

sample 

85 Atlas and 

Schauffler 

1991 

traps with 30–50 μL of 

redistilled benzene in 

3–5 aliquots 

Air Passive collection onto 

carbon-based badge 

(3M OVM 3500); 

extraction with carbon 

GC/MS (SIM) <1 μg/m3 

(0.14 ppb) 

89.3 Otson et al. 

1994 

disulphide containing 

internal standard 
 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 146 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining 1,1,2,2-Tetrachloroethane in 

Environmental Materials
 

Sample Analytical Sample Percent 

matrix Preparation method method detection limit recovery Reference 

Air	 Equilibration of air with GC/MS 0.06 ppbv 70–98 Chai and 

polymer-coated fiber (1.5% RSD) depending on Pawliszyn 

for analyte concen- how fiber is 1995 

tration followed by stored after 

thermal desorption of collection 

fiber (SPME) 

Air	 Direct injection of 1 mL High speed 2 ppb (14 μg/m3) No data Mouradian et 

air into GC and GC/FID (depends on al. 1991 

cryogenic focusing retention time) 

(-150 °C) of volatiles 

followed by rapid 

heating to +150 °C in 

20 minutes. 

Occupational	 Preconcentration of GC/FID 0.01 mg/sample 106 NIOSH 1994 

air	 analyte from air onto (0.3 mg/m3 for 

solid sorbent tube 30 L sample 

(petroleum charcoal); volume) 

desorption with CS2 

and injection of 5 μL 

into GC. Working 

range is 1.5–15 ppm
 

(10–100 mg/m3

) for a 

10 L air sample.
 

(NIOSH Method 1019)
 

Air from Adsorption of analyte Cryofocussing 0.01–0.1 ppb No data Gianti et al.
 

waste and onto Tenax followed by HRGC-MS or (0.07–0.7 μg/m3

) 1984;
 

landfill sites thermal desorption HRGC-ECD LaRegina et al.
 

1986 

Treated and Purge and trap GC/MS <1.0 μg/L 90 Otson 1987 

raw source followed by thermal 

water desorption 

Treated and Purging of sample and GC/FID and 1 μg/L (FID); 24 (HECD) Otson and 

raw source on-column trapping GC/HECD 0.5 μg/L (HECD) Williams 1982 

water 

Finished Purge and trap onto Subambient 0.28–0.41 μg/L 111 at 1 μg/L EPA 1986c 

drinking/raw Tenax/silica/charcoal programsource water followed by thermal mable HRGCdesorption	 MS (EPA 

Method 

524.1)
 

Finished Purge and trap onto Cryofocussing 0.04 μg/L (wide 91 at 0.4– EPA 1986d 

drinking/raw Tenax/silica/charcoal (wide or bore), 0.20 μg/L 10 μg/L (wide 

source water followed by thermal narrow bore) (narrow bore) bore), 100 at 

desorption	 HRGC-MS 0.5 μg/L 

(EPA Method (narrow bore) 

524.2) 
 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 147 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining 1,1,2,2-Tetrachloroethane in 

Environmental Materials
 

Sample Analytical Sample Percent 

matrix Preparation method method detection limit recovery Reference 

Finished Purging of organics GC/PID 0.01 μg/L with 99 (6.8% RSD) EPA 1988b 

drinking from water using inert (10.0 eV ELCD (no 

water, raw gas and trapping onto nominal)/ response from 

source water, a sorbent; thermal ELCD PID) 

or drinking desorption onto GC 

water in any (EPA Method 502.2) 

treatment 

stage 

Drinking Purging of organics GC/ 0.01 μg/L 95 (n=18) at EPA 1988a 

water, raw from water using inert electrolytic 0.40 μg/L 

source water, gas and trapping onto conductivity 

or drinking a sorbent; thermal or GC/microwater in any desorption of coulometric 

treatment compounds onto GC detector 

stage (EPA Method 502.1) 

Water Purge and trap GC/MS 0.02–0.2 μg/L 100 (12% RSD APHA 1989a 

(Standard Methods for n=7) at 

6210D; equivalent to 0.5 μg/L 

EPA Method 524) (narrow bore 

capillary 

column) 

Water Purge and trap GC/PID/ 0.1–0.05 μg/L 99 at 10 μg/L; APHA 1989b 

(Standard Methods ELCD or SD=6.8 μg/L 

6230D; equivalent to microEPA Method 502.2) coulometric 

detector 

Water Addition of isotopically GC/MS 10 μg/L Not available EPA 2001 

labeled analogs of 

compounds of interest 

to the water sample 

followed by purge and 

trap (EPA-EAD 

Method 1624) 

Water Purge and trap GC/MS 0.19 μg/L 101 NEMI 2001 

(ASTM Method D5790) 

Water Purge and trap GC/MS 0.06 μg/L 104 NEMI 1997a 

(Standard Methods 

6200B) 

Water Purge and trap GC/ELCD 0.03 μg/L 88 NEMI 1997b 

(Standard Methods 

6200C) 

Water Purge and trap GC/MS 3 μg/L Not available USGS 1983 

followed by thermal 

desorption 

(USGS-NWQL Method 

O-3115) 
 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 148 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining 1,1,2,2-Tetrachloroethane in 

Environmental Materials
 

Sample Analytical Sample Percent 

matrix Preparation method method detection limit recovery Reference 

Water	 Purge and trap 

(USGS-NWQL Method 

O-4127-96) 

Municipal and Purging of organics 

industrial from water using inert 

waste water gas and trapping onto 

a sorbent. Thermal 

desorption of 

compounds onto GC. 

(EPA Method 601) 

Groundwater Purge and trap (EPA 

and solid Method 8240) 

wastes 

Waste water	 Purge and trap onto 

Tenax/silica followed 

by thermal desorption 

Groundwater Cryogenic trapping of 

and surface analyte released into 

water reduced pressure 

headspace 

(modification of 

vacuum distillation) 

Groundwater	 Purge and trap onto 

Tenax/silica followed 

by thermal desorption 

Fish	 Vacuum distillation and 

cryogenic trapping 

GC/MS 

GC/ 

electrolytic 

conductivity 

or GC/microcoulometric 

detector 

GC/MS 

GC/MS (EPA 

Method 624) 

GC/ECD 

GC/MS (EPACLP Method) 

HRGC/MS 

0.077 μg/L 

30 ng/L 

(depending on 

interferences) 

Groundwater: 

5 μg/L; soil/ 

sediment: 

5 μg/kg. Both 

values for fairly 

clean matrix; 

LODs much worse 

for complex 

wastes 

6.9 μg/L 

1 ng/L 

5 μg/L 

No data 

95–116.7	 USGS 1998 

0.95 c+0.19 EPA 1984a 

where c=true 

value for 

concentration 

in μg/L 

0.93 c+1.76 EPA 1986a 

where c is 

concentration 

in μg/L 

102 at 10– EPA 1982a 

1,000 μg/L 

48	 Comba and 

Kaiser 1983 

No data	 EPA 1987 

No data	 Hiatt 1983 
 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 149 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining 1,1,2,2-Tetrachloroethane in 

Environmental Materials
 

Sample Analytical Sample Percent 

matrix Preparation method method detection limit recovery Reference 

Various fatty Extraction of clear GC/ECD or No data Florisil treated: Daft 1989 

and non-fatty beverages with GC/ELCD 38–122 

foods and isooctane. (mean=80%, 

beverages Homogenization of CV=23%); noncomposited food with Florisil treated: 

>70% fat or oil and 8–89 

direct dilution or (mean=57%, 

melting followed by CV=38%) 

dilution with isooctane. 

Preparation of other 

foods with solid or 

pulpy consistency via 

extraction with 20% 

acetone -5% NaCl in 

25% phosphoric acid 

and isooctane. 

Isooctane analyzed 

directly by GC. 

Extracts from samples 

containing 21–70% fat 

had fat removed using 

Florisil. 

Soil and Purging of sample GC/MS 5 μg/kg No data EPA 1987 

sediment	 suspension in water, 

adsorption of volatiled 

compounds onto 

Tenax/silica followed 

by thermal desorption 

Sediment	 Purge and trap with HRGC/ECD 1 μg/kg 60–82 Amin and 

collection of released Narang 1985 

compounds onto 

Porapak followed by 

desorption with 

methanol 

Sediment	 Extraction of sediment GC/ECD/FID 0.05 μg/g (ppm) 84–86 Amaral et al. 

with methanol followed (7% RSD) 1994 

by transfer of an 

aliquot of methanol 

extract to water for 

purge and trap 

analysis 

Sewage Extraction with GC/ECD 0.08 μg/L (wet) 111 Wilson et al. 

sludge pentane, addition of (10.6% RSD) 1994 

internal standard, 

filtration 
 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 150 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining 1,1,2,2-Tetrachloroethane in 

Environmental Materials
 

Sample Analytical Sample Percent 

matrix Preparation method method detection limit recovery Reference 

Liquid and 

solid waste 

Solid and 

liquid waste 

Groundwater 

and solid 

waste 

Air, water, 

solid waste 

Dispersion of solid and 

viscous samples in a 

glycol followed by 

purge and trap using 

Tenax/silica/ charcoal 

and thermal desorption 

Dispersion of solid and 

viscous samples in a 

glycol followed by 

purge and trap using 

Tenax/silica/ charcoal 

and thermal desorption 

Purge and trap direct 

injection, vacuum 

distillation, or head 

space (EPA-OSW 

8021B) 

Purge and trap 

(aqueous, solid, and 

waste oil), direct 

injection (waste oil), 

automatic static 

headspace (solid), 

closed system vacuum 

distillation (aqueous, 

solid, oil, and tissue), 

or desorption from 

trapping media (air) 

(EPA-OSW 8260B) 

GC/HECD 

(EPA Method 

5030 and 

8010) 

GC/HECD 

and PID in 

series 

GC/HECD 

and/or PID 

GC/MS 

0.3 μg/L 

(groundwater); 

0.3 μg/kg (soil); 

15 μg/L (liquid 

waste); 37.5 μg/kg 

(sludge or solid 

waste) 

0.9 μg/L (water 1– 

5 mg/kg (soil) 

0.01 μg/L 

(HECD); not 

available (PID) 

0.04 μg/L (widebore capillary 

column); 

0.20 μg/L (narrowbore capillary 

column) 

0.95 c+0.19 

where c is 

actual 

concentration 

93 at 6 μg/L 

(water) 

99 (HECD); not 

available (PID) 

91 (wide-bore 

capillary 

column); 

100 (narrowbore capillary 

column) 

EPA 1982b, 

1986b 

Lopez-Avila et 

al. 1987 

EPA 1996b 

EPA 1996a 

a

For liquid samples: ppm = mg/L; ppb = μg/L; ppt = ng/L; for air samples: ppbv = nmoles analyte:liter air 

ECD = electron capture detector; ELCD = electrolytic conductivity detector; FID = flame ionization detector; 

GC = gas chromatography; HECD = hall electrolytic conductivity detector; HRGC = high resolution gas 

chromatography; MC = microcoulometry; MS = mass spectrometry; PID = photoionization detector; RSD = relative 

standard deviation (coefficient of variation); SD = standard deviation; SIM = selected ion monitoring; SPME = solid 

phase microextraction 
 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 151 

7. ANALYTICAL METHODS 

methods can result in shifts in GC retention times and in the alteration of instrumental response in MS 

detection that results from pressure changes in the ion source during elution of the water. 

The most common method for the determination of 1,1,2,2-tetrachloroethane levels in water, sediment, 

soil, and other high solid samples is to purge the compound with an inert gas from the sample directly or 

after suspension of the sample in water, and to trap the purged vapors onto a sorbent trap (purge and trap). 

Subsequent thermal desorption is used for the determination of the analyte concentration. Different 

purging methods have been compared by Melton et al. (1981). Purge and trap methods for source and 

drinking water have also been described by Otson (1987) and Otson and Williams (1982). A purge and 

trap method has even been adapted and applied to highly radioactive waste samples (Tomkins et al. 

1989). Dynamic thermal stripping is a variation of the purge and trap method. It has been shown to 

extend the range of analyte molecular weights that can be accessed using this type of methodology 

(Lesage 1991). The determination of 1,1,2,2-tetrachloroethane can be accomplished by both the purge 

and trap and dynamic thermal stripping methods. Matz and Kesners (1993) have described a "spray and 

trap" method in which the sample is continuously sprayed into a container that is swept with gas to 

transport the volatilized organics to a sorbent trap. Unlike the bubble stripping of purge and trap, the 

spray extraction offers a continuous analyte flux of constant concentration for optimum trapping 

conditions. A publication by Daft (1989) demonstrates the poor accuracy that can result when 

liquid/liquid extraction approaches are applied to samples containing volatile organic compounds. 

Standardized methods used for detection of 1,1,2,2-tetrachloroethane in water samples by purge and trap 

followed by GC/MS include EPA Methods 524.2, 624, and 1624, Standard Methods 6200B and 6200C, 

ASTM Method D5790, and USGS-NWQL Methods O-4127-96 and O-3115 (EPA 1982a, 1986b, 2001a; 

NEMI 1997a, 1997b, 2001; USGS 1983, 1998). Detection limits and percent recoveries for 

determination of this substance in water are 0.02–10 ppb and 88–116.7%, respectively, using these 

methods. EPA-OSW Methods 8021B and 8260B can be applied to solid waste samples. Method 8021B 

uses GC followed by a photoionization detector (PID) and a Hall electron capture detector (HECD) 

connected in series (EPA 1996a, 1996b). 

The two routine quantification methods that provide the lowest detection limits are halogen-specific 

detection (e.g., Hall electrolytic conductivity detector) and MS. Since the compound has four chlorine 

atoms, electron capture detection (ECD) is also very sensitive for this compound. The advantages of 

halogen-specific detectors are they are not only very sensitive, but are also selective for halogencontaining compounds. The mass spectrometer, on the other hand, provides additional confirmation of 
 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 152 

7. ANALYTICAL METHODS 

the presence of a compound through the compound's characteristic fragmentation pattern, and this 

selectivity can be very desirable when the simultaneous quantification of many compounds is required. 

The inability of halogen-specific detectors to detect and quantify nonhalogen compounds can be 

overcome by using other detectors (e.g., photoionization detector) in series (Driscoll et al. 1987; LopezAvila et al. 1987). Atomic emission detectors can provide signals from many elements within the 

molecule (C, H, and Cl for 1,1,2,2-tetrachloroethane) simultaneously (Ryan et al. 1990; Yieru et al. 

1990a, 1990b). A detection limit of 10 pg 1,1,2,2-tetrachloroethane was reported using a helium 

discharge detector in conjunction with GC (Ryan et al. 1990). 

High-resolution gas chromatography (HRGC) with capillary columns is a better method for volatile 

compounds than packed columns because capillary columns provide better resolution of closely eluting 

compounds and increase the sensitivity of detection. Sample purge and on-column cryotrapping can 

eliminate the need for the conventional purge and trap unit and can reduce the time of analysis (Pankow 

and Rosen 1988). Although this approach is most easily accomplished using packed columns, capillary 

columns can provide better separation and method sensitivity. The plugging of the trap (or column) by 

moisture condensation during cryotrapping in an open tubular column can be avoided through the use of a 

very wide bore capillary column; the chromatographic resolution of such a column is inferior to narrow 

bore capillary columns (Mosesman et al. 1987; Pankow and Rosen 1988) and limits the method 

sensitivity. 

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 1,1,2,2-tetrachloroethane 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 1,1,2,2-tetrachloroethane. 

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. 
 

 

 

 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 153 

7. ANALYTICAL METHODS 

7.3.1 Identification of Data Needs 

Methods for Determining Biomarkers of Exposure and Effect. A few methods were found for 

the determination of 1,1,2,2-tetrachloroethane levels of biological matrices. The most sensitive method 

found was that of Ashley et al. (1992) in which the LOD for 1,1,2,2-tetrachloroethane in human blood 

was reported to be 0.005 ppb with a recovery of 116% at 0.063 ppb. Chen et al. (1993) reported methods 

for the determination of this compound in blood and tissues from rats that were used to study the 

toxicokinetics of 1,1,2,2-tetrachloroethane after intra-arterial administration. The LOD reported was 

400 ng/g, depending on the tissue, with 90–100% recovery and an average precision of 1.7% relative 

standard deviation (RSD). The methods for rat tissues should be applicable to human tissues, but have 

not been evaluated. The study of the levels of the parent compound in human blood, urine, or other 

biological matrices can be useful in deriving a correlation between levels of this compound in the 

environment and those in human tissue or body fluid. Such controlled correlation studies are unavailable 

for this compound. 

No metabolite or biomarker of 1,1,2,2-tetrachloroethane from human exposure specific to this compound 

has yet been identified (see Section 3.8). The changes in metabolite concentrations with time in human 

blood, urine, or other appropriate biological medium may be useful in estimating its rate of metabolism in 

humans. In some instances, a metabolite or a biomarker might be useful in correlating the exposure doses 

to the human body burden but, as previously noted, the metabolites are not specific to 1,1,2,2-tetrachloroethane. Such studies on the levels of metabolites/biomarkers in human samples are not available for this 

compound, although metabolic products of this compound from animal and in vitro studies have been 

identified (see Chapter 3) and analytical methods for their quantification are available. The metabolites, 

chloral hydrate, trichloroethanol, trichlorethanol glucuronide, and trichloroacetic acid, have all been 

determined using variations of headspace analysis (Breimer et al. 1974; Christensen et al. 1988; Koppen 

et al. 1988). These compounds are metabolites of TCE that can be formed from 1,1,2,2-tetrachloroethane. 

Reported sensitivities were approximately 20 ng/mL (20 ppb). Assuming a greater abundance in urine of 

metabolites relative to parent compound, these methods might be adequate but this has not been 

demonstrated. Additional methods need to be validated or developed to detect metabolites of 

1,1,2,2-tetrachloroethane after exposures at the MRLs. 

Methods for Determining Parent Compounds and Degradation Products in Environmental 

Media. The occurrence of this compound in environmental media can be used to indicate possible 
 

 

 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 154 

7. ANALYTICAL METHODS 

exposure of humans to this compound through the inhalation of air and ingestion of drinking water and 

foods containing 1,1,2,2-tetrachloroethane. The MRL for intermediate-duration inhalation exposure is 

0.4 ppm (see Section 2.3). Methods for the measurement of 1,1,2,2-tetrachloroethane in air at the ppt 

level and at least 85% accuracy are available (Atlas and Schauffler 1991; Class and Ballschmiter 1987; 

Singh et al. 1981). No new methods are needed for this compound in air. Methods for the measurement 

of 1,1,2,2-tetrachloroethane in drinking water are sensitive to sub-ppb (sub-μg/L) and ppt (ng/L) levels

with 91–100% accuracy (APHA 1989a, 1989b; EPA 1986c, 1988b). No new methods are needed for 

drinking water. Very little information was found for 1,1,2,2-tetrachloroethane in food; additional 

detection methods are needed for foods. 

Although the products of biotic and abiotic processes of this compound in the environment are adequately 

known, no systematic study is available that measures the concentrations of its reaction products in the 

environment. In instances where the product(s) of an environmental reaction is more toxic than the parent 

compound, it is important to know the level of the reaction products in the environment. It is known that 

1,1,2,2-tetrachloroethane degrades under anaerobic conditions (e.g., in anaerobic landfills, leading to 

contamination of groundwater) and via hydrolysis to trichloroethylene (see Section 6.3.2, and Cooper et 

al. [1987] and Haag and Mill [1988]). Hallen et al. (1986) also reported isolating 1,1,2-trichloroethane, 

cis-1,2-dichloroethylene, trans-1,2-dichloroethylene, 1,1-dichloroethylene, and vinyl chloride after 

6 weeks of incubation of 1,1,2,2-tetrachloroethane in a simulated landfill. The analytical methods for the 

determination of the levels of these environmental reaction products of 1,1,2,2-tetrachloroethane are 

available. Drinking water would be expected to be the main route of oral exposure. All of these 

compounds can be measured in drinking water using EPA Method 502.2 (EPA 1988b). Method detection 

limits (μg/L) are stated to be 0.01 for trichloroethylene, not determined for 1,1,2-trichloroethane, 0.01 for 

cis-1,2-dichloroethylene, 0.05 for trans-1,2-dichloroethylene, 0.07 for 1,1-dichloroethylene, and 0.02 for 

vinyl chloride. Precisions were reported to be between 2 and 4% RSD. All of the stated degradation 

products except cis- and trans-1,2-dichloroethylene can be measured in soils and solid wastes using EPA 

method 8240 (EPA 1986a) with practical quantitation limits (PQLs) of approximately 5 μg/L in 

groundwater, 5 μg/kg in soils/sediments, and 0.5 mg/kg in wastes. All of the degradation products except 

cis-1,2-dichloroethylene can be measured in municipal and industrial wastes with PQLs ranging from 

0.02 μg/L for 1,1,2-trichloroethane to 0.18 μg/L for vinyl chloride. Assuming that the concentrations of 

these degradation products are much less than the concentration of 1,1,2,2-tetrachloroethane and knowing 

that the methods for the parent compound are sufficiently sensitive to measure background levels, no 

additional methods are needed at the present time. 
 

 

 

 

1,1,2,2-TETRACHLOROETHANE 155 

7. ANALYTICAL METHODS 

7.3.2 Ongoing Studies 

The Environmental Health Laboratory Sciences Division of the National Center for Environmental 

Health, Centers for Disease Control and Prevention, is developing methods for the analysis of 

1,1,2,2-tetrachloroethane and other volatile organic compounds in blood. These methods use purge and 

trap methodology, HRGC, and magnetic sector MS, which gives detection limits in the low ppt range. 

No other ongoing studies related to analytical methods were identified. 
1,1,2,2-TETRACHLOROETHANE 156 

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1,1,2,2-TETRACHLOROETHANE 157 

8. REGULATIONS AND ADVISORIES
 

The international and national regulations and guidelines regarding 1,1,2,2-tetrachloroethane in air, water, 

and other media are summarized in Table 8-1. 

ATSDR has derived an intermediate-duration oral MRL of 0.5 mg/kg/day for 1,1,2,2-tetrachloroethane 

based on a liver effect (minimal hepatocyte necrosis) in female rats administered the chemical in the diet 

for 14 weeks (NTP 2004a). The MRL was derived using benchmark dose modeling of the critical end 

point. The BMD corresponding to a BMR of 10% extra risk is 82.89 mg/kg/day; the corresponding 

BMDL10 is 53.88 mg/kg/day. An uncertainty factor of 100 (10 for interspecies extrapolation and 10 for 

human variability) was applied to the BMDL10 to calculate the MRL. 

An EPA oral reference dose (RfD) and inhalation reference concentration (RfC) for 1,1,2,2-tetrachloroethane have not been derived. 

The IARC classification for 1,1,2,2-tetrachloroethane is Group 3, not classifiable with regard to its 

carcinogenicity to humans (IARC 2004). The EPA cancer classification for 1,1,2,2-tetrachloroethane is 

Group C, possible human carcinogen (IRIS 2006). The National Toxicology Program has not classified 

1,1,2,2-tetrachloroethane for human carcinogenicity (NTP 2004b). The American Conference of 

Governmental Industrial Hygienists (ACGIH) has classified 1,1,2,2-tetrachloroethane as an 

A3 carcinogen (confirmed animal carcinogen with unknown relevance to humans) (ACGIH 2005). 

OSHA requires employers of workers who are occupationally exposed to 1,1,2,2-tetrachloroethane to 

institute engineering controls and work practices to reduce and maintain employee exposure at or below 

permissible exposure limits (PEL) (OSHA 2006c). The employer must use engineering and work practice 

controls to reduce exposure to or below an 8-hour time-weighted average (TWA) of 5 ppm (OSHA 

2006c). Respirators must be provided and used during the time period necessary to install or implement 

feasible engineering and work practice controls (OSHA 2006c). ACGIH (2005) and NIOSH (2005) 

recommend a TWA exposure limit of 1 ppm for occupational exposure. 

1,1,2,2-Tetrachloroethane is regulated by the Clean Water Effluent Guidelines as stated in Title 40, 

Section 400–475, of the Code of Federal Regulations. For each point source category, 1,1,2,2-tetrachloroethane may be regulated as one of a group of chemicals controlled as Total Toxic Organics, or may 
 

1,1,2,2-TETRACHLOROETHANE 158 

8. REGULATIONS AND ADVISORIES 

have a Zero Discharge Limitation. The point source categories for which 1,1,2,2-tetrachloroethane is 

controlled as a Total Toxic Organic include electroplating, metal finishing, and coil coating; see 

electronic Code of Federal Regulations for a complete listing (NARA 2006). 

EPA regulates 1,1,2,2-tetrachloroethane under the Clean Air Act (CAA) and has designated it as a 

hazardous air pollutant (HAP) (EPA 2006a). 1,1,2,2-Tetrachloroethane is on the list of chemicals 

appearing in "The Emergency Planning and Community Right-to-Know Act of 1986" (EPCRA) (EPA 

2006c) and has been assigned a reportable quantity (RQ) limit of 100 pounds (EPA 2006b). The RQ 

represents the amount of a designated hazardous substance which, when released to the environment, 

must be reported to the appropriate authority. 
 

 

 

1,1,2,2-TETRACHLOROETHANE 159 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to 1,1,2,2-Tetrachloroethane 

Agency Description Information Reference 

INTERNATIONAL 

Guidelines: 

IARC Carcinogenicity classification Group 3a IARC 2004 

WHO Air quality guidelines No data WHO 2000 

Drinking water quality guidelines No data WHO 2004 

NATIONAL 

Regulations and 

Guidelines: 

a. Air 

ACGIH TLV (8-hour TWA) 1 ppmb ACGIH 2005 

EPA AEGL No data EPA 2006h 

Hazardous air pollutant Yes EPA 2006a 

42 USC 7412 

NIOSH REL (10-hour TWA) 1 ppmc,d NIOSH 2005 

IDLH 100 ppmc 

OSHA PEL (8-hour TWA) for general industry 5 ppme OSHA 2006c 

29 CFR 1910.1000 

PEL (8-hour TWA) for construction 5 ppme OSHA 2006b 

industry 29 CFR 1926.55, 

Appendix A 

PEL (8-hour TWA) for shipyard industry 5 ppme OSHA 2006a 

29 CFR 1915.1000 

b. Water 

DOT Marine pollutant Yes DOT 2005 

9 CFR 172.101, 

Appendix B 

EPA Drinking water standards and health EPA 2006i 

advisories 

1-day health advisory for a 10-kg 0.04 mg/L 

child 

10-day health advisory for a 10-kg 0.04 mg/L 

child 

DWEL 

Lifetime 

10-4 Cancer risk 

0.002 mg/L 

3x10-4 mg/L 

0.02 mg/L 

National primary drinking water No data EPA 2003 

standards 

National recommended water quality EPA 2006j 

criteria 

Human health for consumption of 0.17 μg/L 

water + organism 

Human health for consumption of 4.0 μg/L 

organism only 

Toxics criteria for those states not EPA 2006g 

complying with Clean Water Act 40 CFR 131.36 

Section 303(c)(2)(B) for human health 

(10-6 risk for carcinogens) for 

consumption of: 

Water + organism 0.17 μg/L 

Organism only 11 μg/L 
 

 

 

 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 160 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to 1,1,2,2-Tetrachloroethane 

Agency Description Information Reference 

NATIONAL (cont.) 

c. Food 

FDA Bottled drinking water No data FDA 2005a 

21 CFR 165.110 

d. Other 

ACGIH Carcinogenicity classification A3f ACGIH 2005 

EPA Carcinogenicity classification 

Oral slope factor 

Inhalation unit risk 

Group Cg 

2x10-1 per mg/kg/day 

5.8x10-5 per μg/m3 

IRIS 2006 

RfC No data 

RfD No data 

Identification and listing of hazardous U209 EPA 2006k 

waste; hazardous waste number 40 CFR 261, 

Appendix VIII 

Superfund, emergency planning, and 

community right-to-know 

Designated CERCLA hazardous Yes EPA 2006b 

substance 40 CFR 302.4 

Reportable quantity 100 pounds 

Effective date of toxic chemical 01/01/87 EPA 2006c 

release reporting 40 CFR 372.65 

NTP Carcinogenicity classification No data NTP 2004b 

a

Group 3: not classifiable as to carcinogenicity to humans

b

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, liquids, or solids. 

c

Potential occupational carcinogen

d

Skin designation: indicates the potential for dermal absorption; skin exposure should be prevented as necessary 

through the use of good work practices, gloves, coveralls, goggles, and other appropriate equipment.

e

Skin designation 

f

A3: confirmed animal carcinogen with unknown relevance to humans 

g

Group C: possible human carcinogen 

ACGIH = American Conference of Governmental Industrial Hygienists; AEGL = Acute Exposure Guideline Level; 

CERCLA = Comprehensive Environmetnal Response, Compensation, and Liability Act; CFR = Code of Federal 

Regulations; DOT = Department of Transportation; DWEL = drinking water equivalent level; EPA = Environmental 

Protection Agency; FDA = Food and Drug Administration; IARC = International Agency for Research on Cancer; 

IDLH = immediately dangerous to life or health; IRIS = Integrated Risk Information System; MCL = maximum 

contaminant level; MCLG = maximum contaminant level goal; NIOSH = National Institute for Occupational Safety 

and Health; NTP = National Toxicology Program; OSHA = Occupational Safety and Health Administration; 

PEL = permissible exposure limit; REL = recommended exposure limit; RfC = inhalation reference concentration; 

RfD = oral reference dose; STEL = short-term expsoure limit; TLV = threshold limit values; TWA = time-weighted 

average; USC = United States Code; WHO = World Health Organization 
 

 

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1,1,2,2-TETRACHLOROETHANE 189 

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. 
1,1,2,2-TETRACHLOROETHANE 190 

10. GLOSSARY 

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. 

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. 
1,1,2,2-TETRACHLOROETHANE 191 

10. GLOSSARY 

Immunologic Toxicity—The occurrence of adverse effects on the immune system that may result from 

exposure to environmental agents such as chemicals. 

Immunological Effects—Functional changes in the immune response. 

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. 
1,1,2,2-TETRACHLOROETHANE 192 

10. GLOSSARY 

Mortality—Death; mortality rate is a measure of the number of deaths in a population during a specified 

interval of time. 

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. 
1,1,2,2-TETRACHLOROETHANE 193 

10. GLOSSARY 

Physiologically Based Pharmacokinetic (PBPK) Model—Comprised of a series of compartments 

representing organs or tissue groups with realistic weights and blood flows. These models require a 

variety of physiological information: tissue volumes, blood flow rates to tissues, cardiac output, alveolar 

ventilation rates, and possibly membrane permeabilities. The models also utilize biochemical 

information, such as air/blood partition coefficients, and metabolic parameters. PBPK models are also 

called biologically based tissue dosimetry models. 

Prevalence—The number of cases of a disease or condition in a population at one point in time. 

Prospective Study—A type of cohort study in which the pertinent observations are made on events 

occurring after the start of the study. A group is followed over time. 

q1*—The upper-bound estimate of the low-dose slope of the dose-response curve as determined by the 

multistage procedure. The q1* can be used to calculate an estimate of carcinogenic potency, the 

incremental excess cancer risk per unit of exposure (usually μg/L for water, mg/kg/day for food, and 

μg/m3

 for air). 

Recommended Exposure Limit (REL)—A National Institute for Occupational Safety and Health 

(NIOSH) time-weighted average (TWA) 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. 
1,1,2,2-TETRACHLOROETHANE 194 

10. GLOSSARY 

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. 

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. 
1,1,2,2-TETRACHLOROETHANE 195 

10. GLOSSARY 

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. 
1,1,2,2-TETRACHLOROETHANE 196 

10. GLOSSARY 

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1,1,2,2-TETRACHLOROETHANE 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. 
 

 

1,1,2,2-TETRACHLOROETHANE A-2 

APPENDIX A 

MRLs are intended only to serve as a screening tool to help public health professionals decide where to 

look more closely. They may also be viewed as a mechanism to identify those hazardous waste sites that 

are not expected to cause adverse health effects. Most MRLs contain a degree of uncertainty because of 

the lack of precise toxicological information on the people who might be most sensitive (e.g., infants, 

elderly, nutritionally or immunologically compromised) to the effects of hazardous substances. ATSDR 

uses a conservative (i.e., protective) approach to address this uncertainty consistent with the public health 

principle of prevention. Although human data are preferred, MRLs often must be based on animal studies 

because relevant human studies are lacking. In the absence of evidence to the contrary, ATSDR assumes 

that humans are more sensitive to the effects of hazardous substance than animals and that certain persons 

may be particularly sensitive. Thus, the resulting MRL may be as much as 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 and Environmental Medicine, 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 and 

Environmental Medicine, Agency for Toxic Substances and Disease Registry, 1600 Clifton Road NE, 

Mailstop F-32, Atlanta, Georgia 30333. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE A-3 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical Name: 1,1,2,2-Tetrachloroethane 

CAS Numbers: 79-34-5 

Date: June 2008 

Profile Status: Post-Public Third Draft 

Route: [ ] Inhalation [X] Oral 

Duration: [ ] Acute [X] Intermediate [ ] Chronic 

Graph Key: 39 

Species: Rat 

Minimal Risk Level: [0.5] mg/kg/day [ ] ppm 

Reference: NTP. 2004a. NTP technical report on the toxicity studies of 1,1,2,2-tetrachloroethane (CAS 

No. 79-34-5) administered in microcapsules in feed to F433/N rats and B6C3F1 mice. Research Triangle 

Park, NC: National Toxicology Program. TR-49. NIH Publication No. 04-4414. 

Experimental design: Groups of 10 male and 10 female F344/N rats were fed diets containing 0, 268, 

589, 1,180, 2,300, or 4,600 ppm of microencapsulated 1,1,2,2-tetrachloroethane for 14 weeks. The 

reported average daily doses were 0, 20, 40, 80, 170, or 320 mg/kg/day; vehicle control (feed with empty 

microcapsules) and untreated control groups were used for both sexes. End points evaluated throughout 

the study included clinical signs, body weight, and feed consumption. Hematology (12 indices) and 

clinical chemistry (10 indices) were assessed on days 5 and 21 and at the end of the study; urinalyses 

were not performed. Necropsies were performed on all animals and selected organs (liver, heart, right 

kidney, lung, right testis, and thymus) were weighed. Comprehensive histological examinations were 

performed on untreated control, vehicle control, and high dose groups. Tissues examined in the lower 

dose groups were limited to bone with marrow, clitoral gland, liver, ovary, prostate gland, spleen, testis 

with epididymis and seminal vesicle, and uterus. Functional observational batteries (FOBs) 

(21 parameters) were performed on rats in both control groups and the 20, 40, and 80 mg/kg/day groups 

during weeks 4 and 13. Sperm evaluations and vaginal cytology evaluations were performed at 0, 40, 80, 

and 170 mg/kg/day. The sperm evaluations consisted of spermatid heads per testis and per gram testis, 

spermatid counts, and epididymal spermatozoal motility and concentration. The vaginal cytology 

evaluations consisted of percentage of time spent in the various estrus stages and estrous cycle length. 

Effects noted in study and corresponding doses: All rats survived to the end of the study, but clinical 

signs of thinness and pallor were observed in all animals in the 170 and 320 mg/kg/day groups. Final 

body weights were statistically significantly lower than vehicle controls in males at 80, 170, and 

320 mg/kg/day (7, 29, and 65% lower, respectively) and females at 40, 80, 170, and 320 mg/kg/day (3, 9, 

29, and 56% lower, respectively); at 320 mg/kg/day, rats of both sexes lost weight. Feed consumption 

decreased with increasing dose level at 170 and 320 mg/kg/day and may have contributed to the reduced 

body weight gain and weight loss. Results of the FOBs showed no exposure-related findings of 

neurotoxicity. The hematology evaluations indicated that 1,1,2,2-tetrachloroethane affected the 

circulating erythroid mass in both sexes (Table A-1). There was evidence of a transient erythrocytosis, as 

shown by increases in hematocrit values, hemoglobin concentration, and erythrocyte counts on days 5 and 

21 at ≥170 mg/kg/day. The erythrocytosis was not considered clinically significant and disappeared by 

week 14, at which time it was replaced by minimal to mild, dose-related anemia, as shown by decreases 

in hematocrit and hemoglobin at ≥40 mg/kg/day. For example, although males exposed to 40 mg/kg/day 

showed a statistically significant decrease in hemoglobin at week 14, the magnitude of the change was 

small (3.8%). The anemia was characterized as microcytic based on evidence suggesting that the 

circulating erythrocytes were smaller than expected; this included decreases in mean cell volumes, mean 

cell hemoglobin values, and mean cell hemoglobin concentration in both sexes at ≥80mg/kg/day at 
 

1,1,2,2-TETRACHLOROETHANE A-4 

APPENDIX A 

various time points. At week 14, there were no changes in reticulocyte counts, suggesting that there was 

no erythropoietic response to the anemia; this was supported by bone marrow atrophy observed 

microscopically. As discussed by NTP (2004a), the erythrocytosis suggested a physiological response 

consistent with the hemoconcentration of dehydration, and compromised nutritional status due to the 

reduced weight gain and food consumption may have contributed to the development of the anemia. 

Table A-1. Body Weight, Liver Weight, and Selected Serum Chemistry and
 

Hematology Changes in Rats Exposed to 1,1,2,2-Tetrachloroethane in the
 

Diet for 14 Weeksa
 

Vehicle Dose (mg/kg/day) 

End point control 20 40 80 170 320 

Males (10/group) 

Body weight (g) 366±5 354±9 353±6 341±6b 259±9b 127±5b 

Liver weight 

absolute (g) 12.74±0.26 12.99±0.35 14.47±0.44 15.54±0.39 11.60±0.44b 6.57±0.18b 

relative (%) 34.79±0.42 36.72±0.44 41.03±0.85b 45.61±0.52b 44.68±0.45b 52.23±1.42b 

Serum total protein 

(g/dL) 7.2±0.1 7.3±0.1 7.3±0.1 7.3±0.1 6.7±0.1b 6.0±0.1b 

Serum cholesterol 

(mg/dL) 73±2 74±3 76±2 67±2 68±2 65±2b 

ALT (IU/L) 48±2 49±2 53±2 69±3b 115±8b 292±18b 

ALP (IU/L) 256±7 260±5 248±5 245±6 353±12b 432±24b 

SDH (IU/L) 23±1 27±1b 26±2 31±1b 47±2b 74±4b 

Bile acids (μmol/L) 29.2±2.9 27.5±2.7 27.2±2.7 35.9±3.9 92.0±16.6b 332.4±47.4b 

Hematocrit (%) 

(automated) 45.2±0.5 44.9±0.4 44.0±0.9 43.3±0.7 43.1±0.6b 39.0±1.1b 

Hemoglobin (Hb) (g/dL) 15.8±0.1 15.6±0.1 15.2±0.3b 14.9±0.1b 14.6±0.1b 13.6±0.3b 

Mean cell volume (fL) 50.7±0.1 51.8±0.3 52.3±0.2 51.3±0.2 49.4±0.2 44.4±0.4b 

Mean cell Hb (pg) 17.7±0.1 18.1±0.1 18.0±0.1 17.7±0.2 16.8±0.1b 15.5±0.2b 

Platelets (103/μL) 728.4±12.3 707.0±5.8 727.0±25.2 716.3±9.7 692.8±12.6b 773.4±23.2b 
 

 

 

 

1,1,2,2-TETRACHLOROETHANE A-5 

APPENDIX A 

Table A-1. Body Weight, Liver Weight, and Selected Serum Chemistry and
 

Hematology Changes in Rats Exposed to 1,1,2,2-Tetrachloroethane in the
 

Diet for 14 Weeksa
 

Veh Dose (mg/kg/day) icle 

End point control 20 40 80 170 320 

Females (10/group) 

Body weight (g) 195±4 192±4 189±2 177±2b 139±4b 85±3b
 

Liver weight
 

absolute (g) 6.84±0.17 7.03±0.12 7.14±0.16 7.80±0.08b 6.66±0.21 4.94±0.12b 

relative (%) 35.07±0.56 36.69±0.36 37.84±0.51b 44.20±0.27b 48.03±0.89b 58.40±1.42b 

Serum total protein 

(g/dL) 7.2±0.1 7.3±0.0 7.3±0.1 6.9±0.1 6.4±0.1b 5.6±0.1b 

Serum cholesterol 

(mg/dL) 104±4 105±3 98±1 81±2b 64±3b 55±3b 

ALT (IU/L) 46±2 42±1 41±2 49±2 112±7b 339±18b 

ALP (IU/L) 227±5 216±4 220±3 225±11 341±7b 468±22b 

SDH (IU/L) 27±1 27±1 28±2 25±1 45±3b 82±3b 

Bile acids (μmol/L) 37.0±7.1 46.6±6.5 39.1±5.6 36.3±3.9 39.3±7.9 321.5±50.6b 

Hematocrit (%) 

(automated) 42.8±0.4 43.2±0.4 42.1±0.4 40.1±0.5b 42.8±0.7 34.7±0.7b 

Hb (g/dL) 15.2±0.1 15.3±0.1 14.9±0.1 14.2±0.2b 14.5±0.2b 12.5±0.2b 

Mean cell volume (fL) 55.4±0.1 56.1±0.1 55.8±0.1 53.3±0.2b 49.0±0.2b 44.4±0.4b 

Mean cell Hb (pg) 19.7±0.1 19.8±0.1 19.7±0.1 18.9±0.1b 16.6±0.2b 16.0±0.2b 

Platelets (103/μL) 742.1±20.4 725.9±12.7 733.9±8.8 727.4±14.2 639.4±9.9b 662.5±19.4b 

a

Mean±standard error.
 b

Significantly different (p≤0.05) from control value by William’s test (body and liver weight data) or Dunn’s or Shirley’s
 

test (clinical chemistry and hematology data).
 

ALP = alkaline phosphatase; ALT = alanine aminotransferase; SDH = sorbitol dehydrogenase 

Source: NTP 2004a 

Statistically significant increases in absolute and relative liver weights were observed in males and 

females exposed to ≥40 mg/kg/day (Table A-1). Significant alterations in absolute and/or relative 

weights were also observed in several other organs, but these changes likely reflected the decreased body 

weight gain associated with reduced food intake. Changes in serum clinical chemistry parameters 

indicative of liver damage were observed in both sexes, generally occurring at all time points (day 5, 

day 21, and week 14) and generally increasing in magnitude with increasing dose and time. At week 14 

(Table A-1), these effects included statistically significant increases in ALT and SDH in males at 

≥80 mg/kg/day and females at ≥170 mg/kg/day, increases in ALP in both sexes at ≥170 mg/kg/day, 

increases in bile acids in males at ≥170mg/kg/day and females at 320 mg/kg/day, and decreases in serum 

cholesterol in females at ≥80 mg/kg/day and males at 320 mg/kg/day. There were no exposure-related 

changes in serum 5’-nucleotidase at week 14, although increases occurred on day 5 in females at 

≥20 mg/kg/day and on day 21 in males and females at 80, 170, and/or 320 mg/kg/day. As discussed by 

NTP (2004a), increases in ALT and SDH are specific markers of hepatocellular necrosis or increased cell 

membrane permeability (leakage) in rodents; increases in bile acids are markers of cholestasis, impaired 
 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE A-6 

APPENDIX A 

hepatocellular function, or hepatocellular injury; increases in ALP and 5’-nucleotidase are other markers 

of cholestasis; and decreases in serum cholesterol could be indicative of liver dysfunction (impaired 

cholesterol biosynthesis). The LOAEL for serum chemistry effects is 170 mg/kg/day because the 

magnitude of the changes in serum ALT, SDH, and cholesterol at 80 mg/kg/day were less than 2-fold 

different from controls and not considered to be biologically significant. 

Histological evaluation presented further evidence of the liver as the primary target of 1,1,2,2-tetrachloroethane toxicity; a summary of histological changes is presented in Table A-2. Hepatic cytoplasmic 

vacuolization was noted in males exposed to 20 mg/kg/day or more and females exposed to 40 mg/kg/day 

or more. Although the incidence of this alteration was high in affected groups, severity was only 

minimal-to-mild and did not increase with dose. Females exposed to 80 mg/kg/day showed an increase in 

the incidence of hepatocyte hypertrophy, which increased in severity and incidence with increasing 

exposure level; similar results were seen in males, but were not statistically significant below 

170 mg/kg/day. At ≥170 mg/kg/day, additional effects in the liver in both sexes were hepatocyte 

necrosis, pigmentation, mitotic alteration and mixed cell foci, and bile duct hyperplasia. Pigmentation of 

the spleen was increased in male rats exposed to ≥80mg/kg/day and in female rats exposed to 

≥170 mg/kg/day. Other histological effects included high incidences (70–100%) of atrophy in the spleen 

(red pulp and lymphoid follicle) of both sexes at 320 mg/kg/day, bone (metaphysis) and bone marrow in 

females at ≥170 mg/kg/day and males at 320 mg/kg/day, and male and female reproductive tissues at 

320 mg/kg/day. The reductions in body weight gain at 170 mg/kg/day and body weight losses at 

320 mg/kg/day may have contributed to the atrophy of the bone, bone marrow, and reproductive tissues. 

Table A-2. Incidences of Selected Histopathological Lesions in Rats Exposed to 

1,1,2,2-Tetrachloroethane in the Diet for 14 Weeks 

Vehicle Dose (mg/kg/day) 

End point control 20 40 80 170 320 

Males (10/group)a 

Hepatocyte cytoplasmic 

vacuolization 0 

Hepatocyte hypertrophy 0 

Hepatocyte necrosis 0 

Hepatocyte pigmentation 0 

Hepatocyte mitotic alteration 0 

Mixed cell foci 0 

7b (1.3) 

0 

0 

0 

0 

0 

9b (2.0) 

0 

0 

0 

0 

0 

10b (1.9) 8b (1.4) 

1 (1.0) 9b (1.3) 

0 8b (1.0) 

0 7b (1.0) 

0 0 

0 3 

0 

10b (3.2) 

10b (1.6) 

10b (1.9) 

6b (2.0) 

5b 

Bile duct hyperplasia 

Spleen pigmentation 

Spleen red pulp atrophy 

0 

0 

0 

0 

0 

0 

0 

1 (1.0) 

0 

0 0 

9b (1.0) 9b (1.0) 

0 5b (1.0) 

10b (1.7) 

9b (1.6) 

9b (1.4) 

Spleen lymphoid follicle 

atrophy 0 0 0 0 0 5b (1.0) 
 

 

 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE A-7 

APPENDIX A 

Table A-2. Incidences of Selected Histopathological Lesions in Rats Exposed to 

1,1,2,2-Tetrachloroethane in the Diet for 14 Weeks 

Vehicle Dose (mg/kg/day) 

End point control 20 40 80 170 320 

Females (10/group)a 

Hepatocyte cytoplasmic 

vacuolization 0 0 10b (1.7) 10b (2.2) 4b (1.3) 0 

Hepatocyte hypertrophy 0 0 0 4b (1.0) 10b (1.7) 10b (2.8) 

Hepatocyte necrosis 0 0 0 1 (1.0) 7b (1.0) 10b (1.1) 

Hepatocyte pigmentation 0 0 0 0 10b (1.3) 10b (2.0) 

Hepatocyte mitotic alteration 0 0 0 0 3 (2.0) 10b (1.9) 

Mixed cell foci 0 0 0 0 8b 1 

Bile duct hyperplasia 0 0 0 0 5b (1.0) 10b (1.9) 

Spleen pigmentation 1 (1.0) 0 0 4 (1.0) 8b (1.1) 8b (1.3) 

Spleen, red pulp atrophy 0 0 0 0 0 9b (1.6) 

Spleen lymphoid follicle 

atrophy 0 0 0 0 0 3 (1.0) 

a

Values represent number of animals with the lesion, with the severity score in parenthesis; severity grades are as
 

follows: 1=minimal, 2=mild, 3=moderate, 4=severe.

b

Significantly different (p≤0.01) from vehicle control group by the Fisher Exact Test.
 

Source: NTP 2004a 

Reproductive effects in the males included statistically significant reductions in sperm motility at 

≥40 mg/kg/day (18–22% less than vehicle controls), reductions in absolute epididymis weight at 

≥80 mg/kg/day and absolute left cauda epididymis weight at 170 mg/kg/day (relative organ weights not 

reported), and increases in incidences (90–100%) of minimal to moderate atrophy of the prostate gland, 

seminal vesicle, and testicular germinal epithelium at 320 mg/kg/day. Reproductive effects in the females 

included statistically significant increases in incidences (70–100%) of minimal to mild uterine atrophy at 

≥170 mg/kg/day, clitoral gland atrophy at 320 mg/kg/day, and ovarian interstitial cell cytoplasmic 

alterations at 320 mg/kg/day. The vaginal cytology evaluations indicated that the females in the 

170 mg/kg/day group (320 mg/kg/day not evaluated) spent more time in diestrus and less time in 

proestrus, estrus, and metestrus than did the vehicle controls. The body weight loss at 320 mg/kg/day and 

reduced body weight gain at the lower dose levels could have contributed to the atrophy and other effects 

in both sexes. The LOAEL for male rat reproductive effects is 320 mg/kg/day based on atrophy in the 

prostate gland, seminal vesicle, and testicular germinal epithelium. The effects in males at lower doses 

are not judged to be adverse, indicating that the male reproductive NOAEL is 170 mg/kg/day. In 

particular, the male reproductive organ weight decreases at 80 and 170 mg/kg/day are not considered 

adverse due to a lack of accompanying histopathology. The reductions in sperm motility at 

≥40 mg/kg/day are not considered adverse because the decreases are small, not dose-related, not 

accompanied by decreased sperm counts, and of unclear reproductive significance. The LOAEL for 

female rat reproductive effects is 170 mg/kg/day based on uterine atrophy and estrus cycle alterations; the 

corresponding NOAEL is 80 mg/kg/day. 

In summary, this study provides evidence that the liver was the primary target of 1,1,2,2-tetrachloroethane 

toxicity in rats. At the lowest dose tested, 20 mg/kg/day, there was a significant increase in the incidence 

of hepatic cytoplasmic vacuolization in males; this minimal effect, which did not increase in severity with 
 

 

 

 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE A-8 

APPENDIX A 

dose, was not considered adverse by NTP (2004a). At 40 mg/kg/day, significant increases in relative 

liver weights were observed. Hepatocellular hypertrophy, spleen pigmentation, and decreases in body 

weight gain (<10%) were observed at 80 mg/kg/day, although these changes were generally of minimal 

severity or adaptive in nature. Increases in serum ALT and SDH and decreases in serum cholesterol also 

occurred at ≥80 mg/kg/day, but the magnitudes of these changes were biologically significant only at 

≥170 mg/kg/day. Other effects that occurred at 170 and 320 mg/kg/day included increases in serum ALP 

and bile acids, hepatocyte necrosis, bile duct hyperplasia, hepatocellular mitotic alterations, foci of 

cellular alterations, and liver pigmentation. This study identified a NOAEL of 80 mg/kg/day and a 

LOAEL of 170 mg/kg/day for systemic toxicity based on adverse liver-related serum chemistry changes 

and histological manifestations of hepatocellular damage. This LOAEL is lower than or equal to the 

LOAELs for reproductive effects in males (320 mg/kg/day) and females (170 mg/kg/day). A LOAEL for 

neurotoxicity was not identified because there were no clinical signs of neurotoxicity or exposure-related 

findings in the FOB at doses as high as 80 mg/kg/day (highest tested dose in the FOB). These findings 

suggest that the nervous system is less sensitive than the liver for intermediate-duration dietary exposure. 

Dose and end point used for MRL derivation: 

[ ] NOAEL [ ] LOAEL [X] BMDL 

Based on benchmark dose analysis of dose-response data for various liver effects, a BMDL10 of 

53.88 mg/kg/day for hepatocyte necrosis was selected as the point of departure for the MRL. The BMD 

analysis and basis for selection of the point of departure are presented in the last section of this worksheet. 

Uncertainty Factors used in MRL derivation: 

[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? Average daily doses 

were reported by the investigators. 

If an inhalation study in animals, list conversion factors used in determining human equivalent dose: Not 

applicable. 

Was a conversion used from intermittent to continuous exposure? Not applicable (ad libitum dietary 

exposure). 

Other additional studies or pertinent information that lend support to this MRL: The NTP (2004a) study 

also tested mice that were exposed to 1,1,2,2-tetrachloroethane in the diet for 14 weeks. As detailed 

below, this study found that the mice were less sensitive than the rats, as reflected by the liver toxicity 

findings, which identified LOAELs and NOAELs that were higher in the mice (300 and 200 mg/kg/day) 

than in the rats (170 and 80 mg/kg/day). Groups of 10 male and 10 female B6C3F1 mice were exposed to 

diets containing 0, 589, 1,120, 2,300, 4,550, or 9,100 ppm of microencapsulated 1,1,2,2-tetrachloroethane 

for 14 weeks. The reported average daily doses were 0, 100, 200, 370, 700, or 1,360 mg/kg/day for males 

and 80, 160, 300, 600, or 1,400 mg/kg/day for females; vehicle and untreated control groups were used 

for each sex. End points evaluated throughout the study included clinical signs, body weight, and feed 

consumption. Clinical chemistry (10 indices) was assessed at the end of the study; hematology 

evaluations and urinalyses were not performed. Necropsies were conducted on all animals and selected 

organs (liver, heart, right kidney, lung, right testis, and thymus) were weighed. Comprehensive 

histological examinations were performed on untreated control, vehicle control, and high dose groups. 

Tissues examined in the lower dose groups were limited to the liver, spleen, and thymus in both sexes, 
 

 

 

 

1,1,2,2-TETRACHLOROETHANE A-9 

APPENDIX A 

preputial gland in males, and lungs in females. FOBs (21 parameters) were performed on mice in both 

control and 160/200, 300/370, and 600/700 mg/kg/day groups during weeks 4 and 13. Sperm motility, 

vaginal cytology, estrous cycle length, and percentage of time spent in the various estrus stages were 

evaluated in both control and 160/200, 600/700, and 1,360/1,400 mg/kg/day groups. 

All mice survived to the end of the study. A clinical sign of thinness was observed at 300/370 mg/kg/day 

(3/10 males, 1/10 females), 600/700 mg/kg/day (9/10 males, 2/10 females), and 1,360/1,400 mg/kg/day 

(10/10 males, 10/10 females). Final body weights were significantly lower than vehicle controls in male 

mice at 370, 700, and 1,360 mg/kg/day (12, 16, and 33% reduced, respectively) and female mice at 300, 

600, and 1,400 mg/kg/day (4, 10, and 11% reduced, respectively) (Table A-3). Feed consumption was 

slightly less than controls in males at ≥700 mg/kg/day, but similar to controls in females. Significant 

increases in absolute and relative liver weights were observed in the male mice exposed to 200 mg/kg/day 

or higher and in female mice exposed to 80 mg/kg/day or higher (Table A-3). Other organ weight 

changes (increased kidney weights in males at ≥370 mg/kg/day and increased thymus weights in both 

sexes at 1,360/1,400 mg/kg/day) were considered to be secondary to the body weight changes. Results of 

the FOBs showed no exposure-related neurotoxicity. 

Table A-3. Body Weight, Liver Weight, and Selected Clinical Chemistry Changes 

in Mice Exposed to Microencapsulated 1,1,2,2-Tetrachloroethane in the Diet for 

14 Weeksa 

Vehicle Dose (mg/kg/day) 

End point control 100 200 370 700 1,360 

Males (10/group) 

Body weight 

(g) 30.1±0.6 30.6±0.6 30.0±0.3 26.5±0.4b 25.2±0.2b 23.1±0.5b 

Liver weight 

absolute (g) 1.47±0.02 1.56±0.04 1.70±0.02b 1.61±0.04b 1.53±0.05 1.56±0.04 

relative (%) 48.84±1.17 50.94±0.93 56.82±0.63b 60.63±1.20b 60.71±1.76b 67.43±1.83b 

Serum total 

protein (g/dL) 5.4±0.1 5.2±0.1 5.1±0.1b 5.1±0.1b 5.1±0.1b 5.1±0.1b 

Serum 

cholesterol 

(mg/dL) 131±7 125±4 94±3b 110±5 112±4 126±5 

ALT (IU/L) 66±8 62±19 74±8 207±18b 172±18b 296±24b 

ALP (IU/L) 85±2 78±2 89±2 130±3b 143±7b 184±11b 

SDH (IU/L) 55±3 53±2 76±3b 288±20b 288±29b 448±25b 

5’-Nucleotidase (IU/L) 18±1 16±1 18±0 30±2b 37±3b 62±7b 

Bile acids 

(μmol/L) 25.3±1.2 22.8±1.5 24.8±0.6 56.5±5.1b 63.3±7.5b 108.7±8.1b 
 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE A-10 

APPENDIX A 

Table A-3. Body Weight, Liver Weight, and Selected Clinical Chemistry Changes 

in Mice Exposed to Microencapsulated 1,1,2,2-Tetrachloroethane in the Diet for 

14 Weeksa 

Vehicle Dose (mg/kg/day) 

End point control 80 160 300 600 1,400 

Females (10/group) 

Body weight 

(g) 24.3±0.5 24.2±0.2 24.3±0.6 23.3±0.4 21.7±0.2b 21.5±0.6b 

Liver weight 

absolute (g) 1.05±0.03 1.16±0.02b 1.36±0.06b 1.34±0.04b 1.28±0.03b 1.39±0.05b 

relative (%) 43.26±1.05 47.90±0.85b 55.54±1.17b 57.39±0.84b 58.73±1.23b 64.42±1.14b 

Serum total 

protein (g/dL) 5.6±0.1 5.6±0.1 5.5±0.0 5.4±0.1b 5.4±0.0b 5.1±0.1b 

Serum 

cholesterol 

(mg/dL) 109±2 109±3 85±3b 68±2b 64±3b 92±4b 

ALT (IU/L) 34±5 50±15 65±5b 189±33b 197±21b 351±35b 

ALP (IU/L) 131±5 126±2 139±5 150±3b 161±7b 195±6b 

SDH (IU/L) 36±1 44±3b 76±4b 197±15b 243±23b 461±59b 

5’-Nucleotidase (IU/L) 59±3 71±2 84±5b 62±2 62±3 83±4b 

Bile acids 

(μmol/L) 27.2±1.2 26.1±1.9 30.9±1.1b 44.2±3.9b 51.5±3.6b 101.7±12.0b 

a

Mean±standard error.
 b

Statistically significantly different from control value.
 

ALP = alkaline phosphatase; ALT = alanine aminotransferase; SDH = sorbitol dehydrogenase 

Source: NTP 2004a 

Clinical chemistry findings in the mice are summarized in Table A-3 and included statistically significant 

decreases in serum total protein in males at ≥200mg/kg/day, serum total protein in females at 

≥300 mg/kg/day, and serum albumin in females at 1,400 mg/kg/day. Decreased serum albumin could not 

fully account for the decreased total protein concentrations, suggesting that other factors (e.g., changes in 

other protein fractions, hydration status, and/or hepatic function) contributed to the hypoproteinemia 

(NTP 2004a). Other serum chemistry changes were indicative of dose-related liver effects beginning at 

160 mg/kg/day; these included statistically significant increased SDH in both sexes at ≥160/

200 mg/kg/day, decreased serum cholesterol in females at ≥160 mg/kg/day, increased ALT and total bile 

acids in females at ≥160 and males at ≥370 mg/kg/day, increased ALP in both sexes at 300/ 

370 mg/kg/day, and increased 5’-nucleotidase in males at ≥370 mg/kg/day. As previously discussed for 

the rat study, these serum indices are markers of hepatocellular damage, cholestasis, and/or impaired 

hepatic function (NTP 2004a). The magnitudes of the serum chemistry changes were biologically 

significant (e.g., greater than 2-fold increases in serum ALT and SDH) at ≥300 mg/kg/day in females and 

≥370 mg/kg/day in males. 

Histopathological findings are consistent with the serum chemistry data in indicating that the liver is the 

most sensitive target of 1,1,2,2-tetrachloroethane toxicity in the mice. As summarized in Table A-4, 
 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE A-11 

APPENDIX A 

minimal hepatocyte hypertrophy was observed at ≥160 mg/kg/day in females and ≥200 mg/kg/day in 

males. This effect is likely to be an adaptive non-adverse hepatic response. Degenerative and other 

adverse liver lesions, including necrosis, pigmentation, and bile duct hyperplasia, occurred at 

≥300 mg/kg/day in females and ≥370 mg/kg/day in males. Other histological findings included increased 

incidences of preputial gland atrophy in the 100, 700, and 1,360 mg/kg/day male groups (Table A-4), but 

this effect was not clearly dose-related and is possibly associated with decreased body weight gain. 

Based on the adverse serum chemistry and histopathological changes at 300 mg/kg/day and higher doses, 

this study identifies a LOAEL of 300 mg/kg/day for liver toxicity in mice; the corresponding NOAEL is 

200 mg/kg/day. 

Table A-4. Incidences of Selected Histopathological Lesions in Mice Exposed to
 

Microencapsulated 1,1,2,2-Tetrachloroethane in the Diet for
 

14 Weeks 

Vehicle 

End point control 

Males (10/group)a 

Hepatocyte hypertrophy 0 

Hepatocyte necrosis 0 

Liver focal pigmentation 0 

Bile duct hyperplasia 0 

Preputial gland atrophy 0 

100 

0 

0 

0 

0 

4b (2.0) 

Dose (mg/kg/day) 

200 370 700 

7b (1.0) 10b (2.2) 10b (2.8) 

1 (2.0) 8b (1.1) 8b (1.0) 

0 10b (1.2) 10b (1.4) 

0 7b (1.4) 9b (1.3) 

2 (1.0) 0 4b (2.5) 

1,360 

10b (3.1) 

9b (1.0) 

8b (1.3) 

10b (2.0) 

5b (2.2) 

Vehicle 

End point control 

Females (10/group)a 

Hepatocyte hypertrophy 0 

Hepatocyte necrosis 0 

Liver focal pigmentation 0 

Bile duct hyperplasia 0 

80 

2 (1.5) 

0 

0 

0 

Dose (mg/kg/day) 

160 300 600 

9b (1.0) 10b (1.9) 10b (2.5) 

0 3 (1.0) 7b (1.0) 

2 (1.0) 9b (1.0) 8b (1.0) 

0 8b (1.0) 10b (1.4) 

1,400 

10b (3.0) 

4b (1.0) 

7b (1.1) 

10b (2.0) 

a

Values represent number of animals with the lesion, with the severity score in parenthesis; severity grades are as
 

follows: 1=minimal, 2=mild, 3=moderate, 4=severe.

b

Significantly different from vehicle control group.
 

Source: NTP 2004a 

Additional information on the intermediate-duration oral toxicity of 1,1,2,2-tetrachloroethane is available 

from a 21-day gavage study in rats (NTP 1996), a 16-day gavage study in mice (NTP 1993d), 6-week 

gavage studies in rats and mice (NCI 1978), and 15-day diet studies in rats and mice (NTP 2004a). These 

studies are mainly dose range-finding studies that used small numbers of animals and had limited or no 

evaluations of clinical chemistry and histology. Key findings include reduced body weight gain in rats 

exposed to 100 mg/kg/day by gavage for 6 weeks (NCI 1978) or 300 mg/kg/day in the diet for 15 days 

(NTP 2004a), cytoplasmic vacuolation in the liver at 104 mg/kg/day and clinical signs of neurotoxicity 

and mortality at 208 mg/kg/day in rats exposed by gavage for 21 days (NTP 1996), and hepatocellular 

degeneration in mice exposed to 337.5 mg/kg/day by gavage for 16 days (NTP 1993d) or 599 mg/kg/day 

in the diet for 15 days (NTP 2004a). The lowest LOAELs in these studies were 100–104 mg/kg/day for 

reduced body weight gain and hepatocyte cytoplasmic vacuolation in rats exposed by gavage (NCI 1978; 

NTP 1996) and 337.5 mg/kg/day for hepatocellular degeneration in mice exposed by gavage (NTP 
 

 

 

 

1,1,2,2-TETRACHLOROETHANE A-12 

APPENDIX A 

1993d). The NTP (2004a) 14-week dietary study is the best basis for MRL derivation because it tested 

wider ranges of doses and varieties of end points, and identified lower LOAELs, than the other 

intermediate-duration studies. 

Potential points of departure for the intermediate-duration oral MRL were derived by BMD analysis of 

the NTP (2004a) rat liver data in Table A-5. All available dichotomous models in the EPA Benchmark 

Dose Software (BMDS version 1.3.2) were fit to the incidence data for hepatocyte necrosis. The 

continuous-variable models in the software were applied to the data for changes in relative liver weight 

and serum ALT, SDH, bile acids, and cholesterol. 

Table A-5. Selected Liver Effects in Rats Exposed to 1,1,2,2-Tetrachloroethane 

in the Diet for 14 weeks 

Dose (mg/kg/day) 

End point 0 20 40 80 170 320 

Males (10/group) 

Liver weight 

relative (%) 34.79±0.42 36.72±0.44 41.03±0.85b 45.61±0.52b 44.68±0.45b 52.23±1.42b 

Hepatocyte 0 0 0 0 8b 10b 

necrosis 

Serum ALT (IU/L) 48±2 49±2 53±2 69±3b 115±8b 292±18b 

Serum SDH (IU/L) 23±1 27±1b 26±2 31±1b 47±2b 74±4b 

Bile acids 29.2±2.9 27.5±2.7 27.2±2.7 35.9±3.9 92.0±16.6b 332.4±47.4b 

(μmol/L) 

Females (10/group) 

Liver weight 

relative (%) 35.07±0.56 36.69±0.36 37.84±0.51b 44.20±0.27b 48.03±0.89b 58.40±1.42b 

Hepatocyte 0 0 0 1 7b 10b 

necrosis 

Serum ALT (IU/L) 46±2 42±1 41±2 49±2 112±7b 339±18b 

Serum SDH (IU/L) 27±1 27±1 28±2 25±1 45±3b 82±3b 

Bile acids 37.0±7.1 46.6±6.5 39.1±5.6 36.3±3.9 39.3±7.9 321.5±50.6b 

(μmol/L) 

Serum cholesterol 

(mg/dL) 104±4 105±3 98±1 81±2b 64±3b 55±3b 

a

Mean±standard error.
 b

Statistically significantly different from control value.
 

ALT = alanine aminotransferase; SDH = sorbitol dehydrogenase 

Source: NTP 2004a 

For the incidence data, predicted doses associated with 30, 20, 10, 5, and 1% extra risks were calculated 

as possible alternative BMRs for the best fitting model. Conventionally, a 10% extra risk has served as a 

point of departure for MRL determination. However, for a study that examined only 10 animals per 

group, the limit of detection is above the 10% level, likely in the 20–30% range. For the continuous data, 

the BMDs and the 95% lower confidence limits (BMDLs) calculated are estimates of the doses associated 

with a change of 1 standard deviation from the control. Predicted doses associated with an increase of 
 

 

 

 

1,1,2,2-TETRACHLOROETHANE A-13 

APPENDIX A 

100% (i.e., 2-fold) were also calculated for the best fitting model for the changes in liver enzymes (ALT, 

SDH) in the serum, as an increase of this magnitude is sometimes considered to be an indicator of clinical 

significance for these effects. A summary of the predicted BMDs and BMDLs for all of the end points is 

shown in Table A-6. 

Table A-6. Summary of BMD Model Predictions for Rats Exposed to 

1,1,2,2-Tetrachloroethane in the Diet for 14 Weeks 

(Best Fitting Models)
 

End point BMR BMD (mg/kg/day) BMDL (mg/kg/day) 

Males 

Hepatocyte necrosis 10% extra risk 139.31 77.95 

1% extra risk 121.94 46.26 

5% extra risk 133.65 66.47 

20% extra risk 145.73 92.04 

30% extra risk 150.16 102.14 

Relative liver weight 1 control standard deviation No adequate fit to the data 

Serum ALT 1 control standard deviation 38.23 26.56 

100% relative deviation 134.06 121.35 

Serum SDH 1 control standard deviation 36.71 25.13 

100% relative deviation 179.61 152.27 

Bile acids 1 control standard deviation 72.45 57.17 

Females 

Hepatocyte necrosis 10% extra risk 82.89 53.88 

1% extra risk 51.02 22.51 

5% extra risk 70.55 40.85 

20% extra risk 99.76 72.51 

30% extra risk 113.30 87.38 

Relative liver weight 1 control standard deviation No adequate fit to the data 

Serum ALT 1 control standard deviation No adequate fit to the data 

Serum SDH 1 control standard deviation No adequate fit to the data 

Bile acids 1 control standard deviation 216.74 177.00 

Serum cholesterol 1 control standard deviation No adequate fit to the data 

ALT = alanine aminotransferase; BMD = benchmark dose; BMDL = lower confidence limit (95%) on the benchmark 

dose; BMR = benchmark response; SDH = sorbitol dehydrogenase 

Source: NTP 2004a 

The lowest BMDLs were calculated for the male rat serum ALT and SDH data using 1 standard deviation 

below the control mean as the BMR. The BMDLs for serum ALT (26.56 mg/kg/day) and serum SDH 

(25.13 mg/kg/day) are approximately half of the BMDL of 53.88 mg/kg/day calculated using the female 

rat hepatocyte necrosis incidence data and a BMR of 10%. The BMDLs for the serum enzyme changes 

appear to be overly conservative predictions that have questionable biological plausibilty because they are 

substantially below the study NOAEL of 80 mg/kg/day. Effects occurring at the NOAEL included 

increases in serum ALT and SDH that were not biologically significant and hepatocyte necrosis in 

1/10 females. The BMDL of 53.88 mg/kg/day for hepatocyte necrosis was selected as the point of 
 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE A-14 

APPENDIX A 

departure for the MRL because it is reasonably consistent with the observed findings. The intermediateduration oral MRL of 0.5 mg/kg/day was derived by dividing the BMDL by a composite uncertainty 

factor of 100 (10 for extrapolation from humans and 10 for human variability). 

Details of Benchmark Dose Analysis for the Intermediate-duration Inhalation MRL 

Hepatocyte necrosis 

All available dichotomous models in the EPA Benchmark Dose Software (BMDS version 1.3.2) were fit 

to the incidence data for hepatocyte necrosis in male and female rats (Table A-5). Predicted doses 

associated with 30, 20, 10, 5, and 1% extra risks were calculated for the best fitting models. 

As assessed by the chi-square goodness-of-fit test, several models in the software provided adequate fits 

to the data for the incidence of hepatocyte necrosis in male rats (x2 p-value ≥0.1) (Table A-2). Comparing 

across models, a better fit is indicated by a lower Akaike’s Information Criteria value (AIC) (EPA 2000). 

The log-logistic model was determined to be the best-fitting model, as indicated by the AIC for the male 

rat data (Table A-7, Figure A-1), and the gamma model was determined to be the best fit to the female 

data (Table A-8, Figure A-2). Benchmark doses (BMDs and BMDLs) associated with an extra risk of 

10% were calculated for all models. Alternative BMRs of 1, 5, 20, and 30% were calculated from the 

best fitting model for each data set. These are shown in Table A-6. 

Table A-7. Goodness of Fit Statistics and BMD10s and BMDL10s from Models Fit 

to Incidence Data for Hepatocyte Necrosis in Male Rats Exposed to 

1,1,2,2-Tetrachloroethane in the Diet for 14 Weeks 

Degrees of X2 test X2 BMD10 BMDL10 

Model freedom statistic p-valuea AIC (mg/kg/day) (mg/kg/day) 

Gammad 5 12.30 0.9995 12.30 102.95 74.23 

Logistic 4 0.00 1.0000 14.01 154.00 81.87 

Log-Logisticb,e 5 0.00 1.0000 12.01 139.31 77.95 

Multistagec,f 4 0.86 0.9304 13.59 88.60 65.67 

Probit 4 0.00 1.0000 14.01 140.74 78.18 

Log-probite 4 0.00 1.0000 14.01 133.48 76.77 

Quantal-linear 5 12.79 0.0255 32.82 20.50 13.77 

Quantal-quadratic 5 4.56 0.4718 19.68 53.11 41.50 

Weibulld 4 0.00 1.0000 14.01 144.11 76.51 

a

Values <0.1 fail to meet conventional goodness-of-fit criteria b

Best-fitting model c

2-degree polynomial; lowest degree polynomial with adequate fit d

Power restricted to >=1 

e

Slope restricted to >=1 

f

Betas restricted to >=0 

AIC = Akaike’s Information Criteria; BMD = benchmark dose; BMDL = lower confidence limit (95%) on the 

benchmark dose 

Source: NTP 2004a 
 

 

1,1,2,2-TETRACHLOROETHANE A-15 

APPENDIX A 

Figure A-1. Observed and Predicted Incidences of Hepatocyte Necrosis in Male 

Rats Exposed to 1,1,2,2-Tetrachloroethane in the Diet for 14 Weeks*
 

Log-Logistic Model with 0.95 Confidence Level 

Fraction Affected 

1 

0.8 

0.6 

0.4 

0.2 

0 

BMDL BMD 

Log-Logistic 

0 50 100 150 200 250 300 350 

dose 

09:46 04/11 2006 

*BMDs and BMDLs indicated are for a 10% extra risk and are in units of mg/kg/day. 

Source: NTP 2004a 
 

1,1,2,2-TETRACHLOROETHANE A-16 

APPENDIX A 

Table A-8. Goodness of Fit Statistics and BMD10s and BMDL10s from Models Fit 

to Incidence Data for Hepatocyte Necrosis in Female Rats Exposed to 

1,1,2,2-Tetrachloroethane in the Diet for 14 Weeks 

Degrees of X2 test X2 BMD10 BMDL10 

Model freedom statistic p-valuea AIC (mg/kg/day) (mg/kg/day) 

Gammab,d 4 0.11 0.9986 22.89 82.89 53.88 

Logistic 4 0.47 0.9765 23.39 92.95 62.34 

Log-Logistice 4 0.36 0.9853 23.30 84.90 56.41 

Multistagec,f 4 0.14 0.9978 22.95 84.75 49.88 

Probit 4 0.24 0.9933 23.08 87.79 58.48 

Log-probit e 4 0.20 0.9953 23.03 82.69 56.27 

Quantal-linear 5 8.84 0.1156 34.83 20.87 14.04 

Quantal-quadratic 5 1.80 0.8755 23.60 54.34 42.71 

Weibulld 4 0.12 0.9983 22.92 84.37 51.46 

a

Values <0.1 fail to meet conventional goodness-of-fit criteria b

Best-fitting model c

2-degree polynomial; lowest degree polynomial with adequate fit d

Power restricted to >=1 e

Slope restricted to >=1 

f

Betas restricted to >=0 

AIC = Akaike’s Information Criteria; BMD = benchmark dose; BMDL = lower confidence limit (95%) on the 

benchmark dose 

Source: NTP 2004a 
 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE A-17 

APPENDIX A 

Figure A-2. Observed and Predicted Incidences of Hepatocyte Necrosis in
 

Female Rats Exposed to 1,1,2,2-Tetrachloroethane in the Diet for
 

14 Weeks*
 

Gamma Multi-Hit Model with 0.95 Confidence Level 

Fraction Affected 

1 

0.8 

0.6 

0.4 

0.2 

0 

BMDL BMD 

Gamma Multi-Hit 

0 50 100 150 200 250 300 350 

dose 

10:00 04/11 2006 

*BMDs and BMDLs indicated are for a 10% extra risk and are in units of mg/kg/day. 

Source: NTP 2004a 

Continuous Data 

Available continuous-variable models in the EPA Benchmark Dose Software (linear, polynomial, power, 

and Hill models; BMDS version 1.3.2) were fit to the data shown in Table A-5, for changes in relative 

liver weight and serum ALT, SDH, bile acids and cholesterol in male and female rats. The BMDs and the 

95% lower confidence limits (BMDLs) calculated are estimates of the doses associated with a change of 

1 standard deviation from the control. Predicted doses associated with an increase of 100% were also 

calculated for the changes in serum liver enzymes. For the continuous data, the simplest model (linear) 

was applied to the data first while assuming constant variance. If the data were consistent with the 

assumption of constant variance (p-value ≥0.1), then the fit of the linear model to the means was 

evaluated. If the linear model adequately fit the means (p-value ≥0.1), then it was selected as the model

for BMD derivation. If the linear model did not adequately fit the means, then the more complex models 

were fit to the data while assuming constant variance. Among those providing adequate fit to the means 

(p-value ≥0.1), the one with the lowest AIC for the fitted model was selected for BMD derivation. If the

test for constant variance was negative, the linear model was run again while applying the power model 

integrated into the BMDS to account for non-homogenous variance. If the non-homogenous variance 

model provided an adequate fit (p-value ≥0.1) to the variance data, then the fit of the linear model to the
 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE A-18 

APPENDIX A 

means was evaluated. If the linear model did not provide adequate fit to the means while the variance 

model was applied, then the polynomial, power, and Hill models were fit to the data and evaluated while 

the variance model was applied. Among those providing adequate fit to the means (p-value ≥0.1), the one

with the lowest AIC for the fitted model was selected for BMD derivation. If the test for constant 

variance was negative and the non-homogenous variance model did not provide an adequate fit to the 

variance data, then the data set was considered not to be suitable for BMD modeling. 

Relative liver weight 

Statistical tests indicated that variances were not constant across exposure groups (this is reflected in the 

standard errors listed in Table A-5). The non-homogeneous variance model did not adequately fit the 

variance data for either males or females; therefore, there was no good fit to the data for change in relative 

liver weight in either male or female rats (Table A-9). 

Table A-9. Model Predictions for Changes in Relative Liver Weight in Rats 

Exposed to 1,1,2,2-Tetrachloroethane in the Diet for 14 Weeks
 

Variance Means BMD1sd BMDL1sd 

Model p-valuea p-valueb (mg/kg/day) (mg/kg/day) 

Male 

Linear (constant variance) <0.0001 <0.0001 68.02 56.64 

Linear (modeled variance) 0.0255 <0.0001 55.05 37.77 

Female 

Linear (constant variance) <0.0001 0.0063 36.16 30.95 

Linear (modeled variance) 0.0076 0.0004 22.21 14.61 

a

Values <0.05 fail to meet conventional goodness-of-fit criteria b

Values <0.10 fail to meet conventional goodness-of-fit criteria 

BMD = benchmark dose; BMDL = lower confidence limit (95%) on the benchmark dose 

Source: NTP 2004a 

Serum ALT 

For the serum ALT data, the assumption of constant variance did not hold for either the male or female 

data. The non-homogeneous variance model was applied and provided adequate fit to the variance for 

both the male and female data. With the variance model applied, the linear model did not provide 

adequate fit to the means for either the male or female data. For the males, both the polynomial and 

power models provided adequate fit to the means while the variance model was applied. The AIC was 

slightly lower for the polynomial model, which was selected as the best fitting model. Doses associated 

with a 100% change from the control (2-fold) from the polynomial model were also calculated 

(Table A-10, Figure A-3). For the females, none of the models were able to provide adequate fit to the 

means while the variance model was applied. 
 

 

1,1,2,2-TETRACHLOROETHANE A-19 

APPENDIX A 

Table A-10. Model Predictions for Changes in Serum ALT in Rats Exposed to 

1,1,2,2-Tetrachloroethane in the Diet for 14 Weeks 

Variance Means BMD BMDL 

Model BMR p-valuea p-valueb AIC (mg/kg/day) (mg/kg/day) 

Male 

Linear (constant variance) 1 sd <0.0001 <0.0001 484.88 43.91 37.37 

Linear (modeled variance) 1 sd 0.7223 <0.0001 412.89 12.72 10.07 

Polynomialc,d (modeled 

variance) 1 sd 0.7223 0.7302 367.955 38.23 26.56 

100% 0.7223 0.7302 367.955 134.06 121.35 

Powere (modeled variance) 1 sd 0.6731 0.7945 367.956 41.97 32.24 

Hillf (modeled variance) NA 

Female 

Linear (constant variance) 1 sd <0.0001 <0.0001 511.01 44.94 38.22 

Linear (modeled variance) 1 sd 0.1849 <0.0001 447.29 17.59 13.50 

Polynomialg (modeled 

variance) 1 sd 0.1849 <0.0001 370.32 49.47 45.00 

Powere (modeled variance) 1 sd 0.1782 0.0074 358.41 64.68 56.13 

Hillf (modeled variance) NA 

a

Values <0.05 fail to meet conventional goodness-of-fit criteria b

Values <0.10 fail to meet conventional goodness-of-fit criteria c

Best-fitting model d

2-degree polynomial; lowest degree polynomial with adequate fit e

Power restricted to >=1 

f

N restricted to >1 

g

2-degree polynomial; no adequate fit with any polydegree 

AIC = Akaike’s Information Criteria; BMD = benchmark dose; BMDL = lower confidence limit (95%) on the benchmark 

dose; NA = not available (BMD software could not generate a model output); sd = standard deviation 

Source: NTP 2004a 
 

 

 

 

1,1,2,2-TETRACHLOROETHANE A-20 

APPENDIX A 

Figure A-3. Changes in Serum ALT in Male Rats Exposed to 1,1,2,2-Tetrachloroethane in the Diet for 14 Weeks* 

Polynomial Model with 0.95 Confidence Level 

350 

300 

250 

200 

150 

100 

50 

Mean Response 

BMDL BMD 

Polynomial 

0 50 100 150 200 250 300 350 

dose 

08:17 04/13 2006 

*BMDs and BMDLs indicated are associated with a change of 1 standard deviation from the control, and are in units 

of mg/kg/day. 

Source: NTP 2004a 

Serum SDH 

For the serum SDH data, the assumption of constant variance did not hold for either the male or female 

data. The non-homogeneous variance model was applied and provided marginally adequate fit to the 

variance for both the male and female data. With the variance model applied, the linear model did not 

provide adequate fit to the means for either the male or female data. For the males, both the polynomial 

and power models provided adequate fit to the means while the variance model was applied. The AIC 

was slightly lower for the polynomial model, which was selected as the best fitting model. Doses 

associated with a 100% change from the control (2-fold) from the polynomial model were also calculated 

(Table A-11, Figure A-4). For the females, none of the models were able to provide adequate fit to the 

means while the variance model was applied. 
 

 

 

1,1,2,2-TETRACHLOROETHANE A-21 

APPENDIX A 

Table A-11. Model Predictions for Changes in Serum SDH in Rats Exposed to 

1,1,2,2-Tetrachloroethane in the Diet for 14 Weeks 

Model 

Male 

BMR 

Variance 

p-valuea 

Means 

p-valueb AIC 

BMD 

(mg/kg/day) 

BMDL 

(mg/kg/day) 

Linear (constant variance) 1 sd <0.0001 0.1889 291.96 41.70 35.55 

Linear (modeled variance) 

Polynomialc,d (modeled 

variance) 

1 sd 

1 sd 

0.0499 

0.0499 

0.0471 

0.3259 

274.89 

270.72 

23.86 

36.70 

19.11 

25.13 

100% 0.0499 0.3259 270.72 179.61 152.27 

Powere (modeled variance) 

Hillf (modeled variance) 

1 sd 

NA 

0.0499 0.3044 270.89 44.40 28.51 

Female 

Linear (constant variance) 1 sd <0.0001 <0.0001 319.64 47.70 40.47 

Linear (modeled variance) 1 sd 0.0429 <0.0001 310.32 34.45 26.54 

Polynomialg (modeled 

variance) 

Powere (modeled variance) 

Hillf (modeled variance) 

1 sd 

1 sd 

NA 

0.0429 

0.0429 

0.0018 

0.0018 

283.22 

285.20 

92.47 

90.68 

69.39 

70.92 

a

Values <0.05 fail to meet conventional goodness-of-fit criteria b

Values <0.10 fail to meet conventional goodness-of-fit criteria c

Best-fitting model d

2-degree polynomial; lowest degree polynomial with adequate fit e

Power restricted to >=1 

f

N restricted to >1 

g

2-degree polynomial; no adequate fit with any polydegree 

AIC = Akaike’s Information Criteria; BMD = benchmark dose; BMDL = lower confidence limit (95%) on the benchmark 

dose; NA = not available (BMD software could not generate a model output); sd = standard deviation 

Source: NTP 2004a 
 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE A-22 

APPENDIX A 

Figure A-4. Changes in Serum SDH in Male Rats Exposed to 1,1,2,2-Tetrachloroethane in the Diet for 14 Weeks* 

Polynomial Model with 0.95 Confidence Level 

Mean Response 

80 

70 

60 

50 

40 

30 

20 

BMDL BMD 

Polynomial 

0 50 100 150 200 250 300 350 

dose 

23:37 04/17 2006 

*BMDs and BMDLs indicated are associated with a change of 1 standard deviation from the control, and are in units 

of mg/kg/day. 

Source: NTP 2004a 

Bile acids 

For the serum bile acids data, the assumption of constant variance did not hold for either the male or 

female data. The non-homogeneous variance model was applied and provided adequate fit to the variance 

for both the male and female data. With the variance model applied, the Linear and Hill models did not 

provide adequate fit to the means for either the male or female data, and the Polynomial model did not 

provide adequate fit to the mean for the female data. For the males, both the Polynomial and Power 

models provided adequate fit to the means while the variance model was applied. The Power model was 

selected as the best fitting model for the male data because it had a slightly lower AIC than the 

Polynomial model (Table A-12, Figure A-5). For the females, the Power model was the only model that 

provided adequate fit to the means while the variance model was applied (Table A-12, Figure A-6). 
 

1,1,2,2-TETRACHLOROETHANE A-23 

APPENDIX A 

Table A-12. Model Predictions for Changes in Bile Acids in Rats Exposed to 

1,1,2,2-Tetrachloroethane in the Diet for 14 Weeks 

Variance Means BMD BMDL 

Model BMR p-valuea p-valueb AIC (mg/kg/day) (mg/kg/day) 

Male 

Linear (constant variance) 1sd <0.0001 0.0013 577.11 79.44 61.93 

Linear (modeled variance) 1sd 0.7661 <0.0001 464.43 24.81 20.06 

Polynomialc (modeled 

variance) 1sd 0.7661 0.1194 428.95 58.37 49.57 

Powerd,e (modeled variance) 1sd 0.7661 0.4582 427.70 72.45 57.17 

Hillf (modeled variance) NA 

Female 

Linear (constant variance) 1sd <0.0001 <0.0001 594.57 101.36 81.28 

Linear (modeled variance) 1sd 0.4663 <0.0001 576.14 NA 54.83 

Polynomialg (modeled 

variance) 1sd 0.4663 <0.0001 487.96 149.50 106.40 

Powerd,e (modeled variance) 1sd 0.4663 0.3751 466.68 216.74 177.00 

Hillf (modeled variance) NA 

a

Values <0.05 fail to meet conventional goodness-of-fit criteria b

Values <0.10 fail to meet conventional goodness-of-fit criteria c

2-degree polynomial; lowest degree polynomial with adequate fit d

Best-fitting model e

Power restricted to >=1 

f

N restricted to >1 

g

2-degree polynomial; no adequate fit with any polydegree 

AIC = Akaike’s Information Criteria; BMD = benchmark dose; BMDL = lower confidence limit (95%) on the benchmark 

dose; NA = not available (BMD software could not generate a model output) 

Source: NTP 2004a 
 

 

 

1,1,2,2-TETRACHLOROETHANE A-24 

APPENDIX A 

Figure A-5. Changes in Bile Acids in Male Rats Exposed to 1,1,2,2-Tetrachloroethane in the Diet for 14 Weeks* 

Power Model with 0.95 Confidence Level 

400
 

300
 

200
 

100
 

0
 

dose
 

19:25 04/18 2006
 

*BMDs and BMDLs indicated are associated with a change of 1 standard deviation from the control, and are in units 

of mg/kg/day. 

Source: NTP 2004a Mean Response 

BMDL BMD 

Power 

0 50 100 150 200 250 300 350
 
 

 

 

1,1,2,2-TETRACHLOROETHANE A-25 

APPENDIX A 

Figure A-6. Changes in Bile Acids in Female Rats Exposed to 1,1,2,2-Tetrachloroethane in the Diet for 14 Weeks* 

Power Model with 0.95 Confidence Level 

450
 

400
 

350
 

300
 

250
 

200
 

150
 

100
 

50
 

0
 

Mean Response 

BMDL BMD 

Power 

0 50 100 150 200 250 300 350 

dose 

19:08 04/18 2006 

*BMDs and BMDLs indicated are associated with a change of 1 standard deviation from the control, and are in units 

of mg/kg/day. 

Source: NTP 2004a 

Serum cholesterol (females only) 

Statistical tests indicated that variances were not constant across exposure groups (this is reflected in the 

standard deviations listed in Table A-5). The non-homogeneous variance model did not adequately fit the 

variance data; therefore, there was no good fit to the data for change in serum cholesterol in female rats 

(Table A-13). 
 

1,1,2,2-TETRACHLOROETHANE A-26 

APPENDIX A 

Table A-13. Model Predictions for Changes in Serum Cholesterol in Female Rats
 

Exposed to 1,1,2,2-Tetrachloroethane in the Diet for 14 Weeks
 

Variance Means BMD1sd BMDL1sd 

Model p-valuea p-valueb (mg/kg/day) (mg/kg/day) 

Female 

Linear (constant variance) 0.0044 <0.0001 63.66 53.24 

Linear (modeled variance) 0.0019 <0.0001 56.37 39.96 

a

Values <0.05 fail to meet conventional goodness-of-fit criteria b

Values <0.10 fail to meet conventional goodness-of-fit criteria 

BMD = benchmark dose; BMDL = lower confidence limit (95%) on the benchmark dose 

Source: NTP 2004a 

Agency Contacts (Chemical Managers): Jessilynn Taylor, Henry Abadin, and Eugene Demchuk 
 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 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 
 

 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE B-2 

APPENDIX B 

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. 

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. 
 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE 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, 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE B-4 

APPENDIX B 

which was used to derive an intermediate exposure, inhalation MRL of 0.005 ppm (see 

footnote "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. 
 

 

1,1,2,2-TETRACHLOROETHANE 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. 
SAMPLE

1 → Table 3-1. Levels of Significant Exposure to [Chemical x] – Inhalation 

LOAEL (effect) Exposure 

Key to frequency/ NOAEL Less serious Serious (ppm) figurea Species duration System (ppm) (ppm) Re

2 3 4 

→ INTERMEDIATE EXPOSURE 

5 6 7 8 9 10 

→ Systemic ↓ ↓ ↓ ↓ ↓ ↓

18 Rat 13 wk Resp 3b 10 (hyperplasia) 

→ 5 d/wk Nit

6 hr/d 

CHRONIC EXPOSURE 

Cancer 11 

↓

38 Rat 18 mo 20 (CEL, multiple Wo

5 d/wk organs) 7 hr/d 

39 Rat 89–104 wk 10 (CEL, lung tumors, NT

5 d/wk nasal tumors) 6 hr/d 

40 Mouse 79–103 wk 10 (CEL, lung tumors, NT

5 d/wk hemangiosarcomas) 6 hr/d 

12 → 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 ex

by an uncertainty factor of 100 (10 for extrapolation from animal to humans, 10 for human variability). 

1,1,2,2-TETRACHLOROETHANE B-8 

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1,1,2,2-TETRACHLOROETHANE 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 
 

 

1,1,2,2-TETRACHLOROETHANE C-2 

APPENDIX C 

DOT/UN/ Department of Transportation/United Nations/ 

NA/IMDG North America/Intergovernmental 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 
 

 

1,1,2,2-TETRACHLOROETHANE 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 
 

 

 

1,1,2,2-TETRACHLOROETHANE 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 
 

1,1,2,2-TETRACHLOROETHANE C-5 

APPENDIX C 

> greater than ≥ greater than or equal to 

= equal to 

< less than ≤ less than or equal to 

% percent α alpha β beta γ gamma δ delta 

μm micrometer 

μg microgram q1

* cancer slope factor 

– negative 

+ positive 

(+) weakly positive result 

(–) weakly negative result 
1,1,2,2-TETRACHLOROETHANE C-6 

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1,1,2,2-TETRACHLOROETHANE D-1 

APPENDIX D. INDEX
 

absorbed dose.................................................................................................................... 76, 77, 81, 89, 106
 

acetylcholinesterase ....................................................................................................................................15
 

adrenals ........................................................................................................................................... 34, 59, 90
 

adsorbed....................................................................................................................................................142
 

adsorption.......................................................................................................................... 117, 144, 145, 149
 

aerobic............................................................................................................................................... 128, 138
 

alanine aminotransferase (see ALT) ..................................................................................................... 13, 32
 

ALT (see alanine aminotransferase) ............................................................................. 13, 17, 18, 19, 57, 58
 

ambient air ............................................................................................................................ 9, 104, 121, 139
 

anaerobic................................................................................................................... 119, 127, 128, 137, 154
 

anemia.........................................................................................................................................................32
 

aspartate aminotransferase (see AST).........................................................................................................13
 

AST (see aspartate aminotransferase)................................................................................................... 13, 57
 

bioaccumulation........................................................................................................................................138
 

bioavailability ................................................................................................................................... 138, 139
 

bioconcentration factor ............................................................................................................. 126, 133, 138
 

biodegradation....................................................................................................... 9, 119, 126, 127, 128, 137
 

biomarker .............................................................................................................................. 88, 89, 141, 153
 

blood cell count...........................................................................................................................................32
 

body weight effects........................................................................................................... 34, 59, 60, 62, 101
 

breast milk............................................................................................................................... 5, 88, 135, 139
 

cancer.................................................................................. 11, 14, 22, 38, 62, 63, 87, 94, 96, 100, 104, 157
 

carcinogen......................................................................................................................... 4, 14, 63, 157, 160
 

carcinogenic .......................................................................................................... 14, 21, 22, 62, 83, 84, 100
 

carcinogenicity........................................................................................ 4, 14, 19, 38, 63, 83, 100, 157, 160
 

carcinoma............................................................................................................................ 11, 14, 58, 63, 96
 

cardiac arrhythmia ......................................................................................................................................92
 

cardiovascular ................................................................................................................................. 31, 62, 64
 

cardiovascular effects............................................................................................................................ 31, 56
 

chromosomal aberrations...................................................................................................................... 68, 69
 

clearance .....................................................................................................................................................92
 

death.................................................................... 12, 16, 21, 23, 39, 56, 58, 62, 63, 92, 94, 96, 98, 102, 103
 

deoxyribonucleic acid (see DNA)...............................................................................................................11
 

dermal effects.................................................................................................................................. 23, 59, 64
 

developmental effects ............................................................................................... 37, 62, 65, 96, 102, 107
 

DNA (see deoxyribonucleic acid)............................... 11, 13, 57, 66, 67, 68, 69, 75, 76, 81, 83, 84, 89, 100
 

endocrine......................................................................................................................................... 34, 59, 85
 

endocrine effects................................................................................................................................... 34, 59
 

fetus.............................................................................................................................................................86
 

gastrointestinal effects .......................................................................................................................... 31, 56
 

general population............................................................................................. 3, 10, 88, 104, 121, 134, 137
 

genotoxic..................................................................................................................... 14, 21, 65, 83, 89, 100
 

genotoxicity............................................................................................................................. 14, 65, 83, 100
 

germinal epithelium ............................................................................................................................ 61, 101
 

groundwater .............................................. 2, 9, 119, 121, 124, 126, 127, 132, 136, 137, 138, 139, 150, 154
 

half-life.................................................................................................................... 9, 88, 121, 125, 126, 127
 

hematological effects ...................................................................................................................... 32, 56, 96
 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1,1,2,2-TETRACHLOROETHANE D-2 

APPENDIX D 

hepatic effects ....................................................................................... 11, 12, 13, 15, 17, 32, 57, 70, 96, 97
 

hydrolysis.............................................................................................................. 9, 119, 127, 128, 137, 154
 

hydroxyl radical .................................................................................................................... 9, 121, 125, 126
 

immune system .........................................................................................................................................102
 

immunological .................................................................................... 11, 15, 21, 34, 60, 64, 65, 94, 96, 102
 

LD50........................................................................................................................................... 39, 63, 96, 98
 

leukemia........................................................................................................................................ 38, 94, 104
 

lymphatic .............................................................................................................................................. 38, 62
 

lymphoreticular............................................................................................................. 34, 60, 64, 65, 94, 96
 

milk ........................................................................................................................................... 5, 88, 90, 135
 

musculoskeletal effects...............................................................................................................................39
 

neonatal............................................................................................................................................... 37, 101
 

neoplastic ....................................................................................................................................................83
 

neurobehavioral..................................................................................................................................... 12, 85
 

neurological effects............................................................................. 11, 12, 35, 61, 65, 82, 87, 94, 98, 103
 

neurotransmitter ..........................................................................................................................................82
 

nuclear............................................................................................................................... 72, 74, 81, 84, 105
 

ocular effects................................................................................................................................... 34, 59, 64
 

partition coefficients ..................................................................................................................... 71, 75, 135
 

pharmacodynamic.......................................................................................................................................78
 

pharmacokinetic.......................................................................................................... 78, 79, 80, 84, 86, 105
 

rate constant .............................................................................................................................. 121, 125, 126
 

renal effects..................................................................................................................................... 33, 58, 64
 

reproductive effects............................................................................................... 17, 36, 61, 65, 96, 98, 101
 

respiratory effects.................................................................................................................................. 23, 56
 

retention ................................................................................................................................ 70, 76, 146, 151
 

solubility .....................................................................................................................................................71
 

systemic effects....................................................................................................... 23, 32, 39, 64, 94, 96, 99
 

T3.......................................................................................................................................................... 24, 40
 

thyroid....................................................................................................................................... 34, 59, 90, 96
 

toxicokinetic................................................................................................................................ 21, 106, 153
 

tremors ...................................................................................................................................... 35, 65, 94, 96
 

tumors ....................................................................................................................................... 4, 19, 83, 100
 

vapor pressure ...........................................................................................................................................126
 

volatility................................................................................................................................................ 10, 66
 

volatilization ....................................................................................................................... 68, 119, 121, 125