TOXICOLOGICAL PROFILE FOR 

1,2-DICHLOROETHANE 

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
 

Public Health Service
 

Agency for Toxic Substances and Disease Registry
 

September 2001 
1,2-DICHLOROETHANE 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. 
1,2-DICHLOROETHANE iii 

UPDATE STATEMENT
 

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

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

Agency for Toxic Substances and Disease Registry
 

Division of Toxicology/Toxicology Information Branch
 

1600 Clifton Road NE, E-29
 

Atlanta, Georgia 30333
 


1,2-DICHLOROETHANE vi 

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 prepared toxicological profiles for hazardous substances most commonly 

found at facilities on the CERCLA National Priorities List and that pose the most significant potential 

threat to human health, as determined by ATSDR and the EPA. The availability of the revised priority 

list of 275 hazardous substances was announced in the Federal Register on November 17, 1997 (62 FR 

61332). For prior versions of the list of substances, see Federal Register notices dated April 29, 1996 (61 

FR 18744); April 17, 1987 (52 FR 12866); October 20, 1988 (53 FR 41280); October 26, 1989 (54 FR 

43619); October 17, 1990 (55 FR 42067); October 17, 1991 (56 FR 52166); October 28, 1992 (57 FR 

48801); and February 28, 1994 (59 FR 9486). Section 104(i)(3) of CERCLA, as amended, directs the 

Administrator of ATSDR to prepare a toxicological profile for each substance on the list. 
 

 

1,2-DICHLOROETHANE vii 

QUICK REFERENCE FOR HEALTH CARE PROVIDERS 

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

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

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

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

answers to often-asked questions. 

Primary Chapters/Sections of Interest 

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

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

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

the general health effects observed following exposure. 

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

assesses the significance of toxicity data to human health. 

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

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

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

reported in this section. 

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

the clinical setting. Please refer to the Public Health Statement to identify 

general health effects observed following exposure. 

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

issues: 

Section 1.6 How Can (Chemical X) Affect Children? 

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

Section 3.7 Children’s Susceptibility 

Section 6.6 Exposures of Children 

Other Sections of Interest: 

Section 3.8 Biomarkers of Exposure and Effect 

Section 3.11 Methods for Reducing Toxic Effects 

ATSDR Information Center 

Phone: 1-888-42-ATSDR or (404) 639-6357 Fax: (404) 639-6359 

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

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

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

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

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

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

Toxicity; and numerous chemical-specific case studies. 
1,2-DICHLOROETHANE viii 

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

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

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

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

Guidelines for Acute Chemical Exposures—is a guide for health care professionals treating patients 

exposed to hazardous materials. 

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

Other Agencies and Organizations 

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

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

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

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

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

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

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

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

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

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

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

• Phone: 800-35-NIOSH. 

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

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

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

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

Referrals 

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

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

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

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

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

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

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

60005 • Phone: 847-228-6850 • FAX: 847-228-1856. 
1,2-DICHLOROETHANE ix 

CONTRIBUTORS 

CHEMICAL MANAGER(S)/AUTHORS(S):
 

Malcolm Williams, D.V.M., Ph.D.
 

ATSDR, Division of Toxicology, Atlanta, GA
 

Stephen Bosch, M.S.
 

Mario Citra, Ph.D.
 

Syracuse Research Corporation, North Syracuse, NY
 

THE PROFILE HAS UNDERGONE THE FOLLOWING ATSDR INTERNAL REVIEWS:
 

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

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

end points. 

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

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

profile, and makes recommendations for derivation of MRLs. 

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

consistency across profiles and adherence to instructions in the Guidance. 

1,2-DICHLOROETHANE xi 

PEER REVIEW
 

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

members: 

1.	 Dr. G.A. Shakeel Ansari, Department of Human Biological Chemistry & Genetics and Pathology, 

University of Texas Medical Branch, Galveston, TX; 

2.	 Dr. John L. Egle, Department of Pharmacology and Toxicology, Medical College of Virginia, 

Virginia Commonwealth University, Richmond, VA; 

3.	 Dr. F. Peter Guengerich, Center in Molecular Toxicology, Department of Biochemistry, Vanderbilt 

University School of Medicine, Nashville, TN; and 

4.	 Mr. Lyman K. Skory, Skory Consulting, Inc., Health, Environmental and Regulatory Consulting, 

Midland, MI. 

These experts collectively have knowledge of 1,2-dichloroethane's physical and chemical properties, 

toxicokinetics, key health end points, mechanisms of action, human and animal exposure, and 

quantification of risk to humans. All reviewers were selected in conformity with the conditions for peer 

review specified in Section 104(I)(13) of the Comprehensive Environmental Response, Compensation, 

and Liability Act, as amended. 

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

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

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

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

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

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

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

1,2-DICHLOROETHANE xiii 

CONTENTS
 

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

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

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

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

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

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

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

1.1	 WHAT IS 1,2-DICHLOROETHANE? ........................................... 1 
 

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

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

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

1.4	 HOW CAN 1,2-DICHLOROETHANE ENTER AND LEAVE MY BODY? ............. 4 
 

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

1.6	 HOW CAN 1,2-DICHLOROETHANE AFFECT CHILDREN? ........................ 6 
 

1.7	 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO 

1,2-DICHLOROETHANE? .................................................... 7 
 

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

TO 1,2-DICHLOROETHANE? ................................................. 8 
 

1.9	 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO
 

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

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

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

2.1	 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO 1,2-DICHLOROETHANE 

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

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

2.3 	 MINIMAL RISK LEVELS ................................................... 18 
 

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

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

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

3.2.1 Inhalation Exposure .................................................. 23 
 

3.2.1.1 Death ..................................................... 37 
 

3.2.1.2 Systemic Effects ............................................ 38 
 

3.2.1.3 Immunological and Lymphoreticular Effects ...................... 44 
 

3.2.1.4 Neurological Effects ......................................... 45 
 

3.2.1.5 Reproductive Effects ......................................... 46 
 

3.2.1.6 Developmental Effects ....................................... 47 
 

3.2.1.7 Cancer .................................................... 48 
 

3.2.2 Oral Exposure ...................................................... 49 
 
1,2-DICHLOROETHANE xiv 

3.2.2.1 Death ..................................................... 50 
 

3.2.2.2 Systemic Effects ............................................ 72 
 

3.2.2.3 Immunological and Lymphoreticular Effects ...................... 79 
 

3.2.2.4 Neurological Effects ......................................... 80 
 

3.2.2.5 Reproductive Effects ......................................... 82 
 

3.2.2.6 Developmental Effects ....................................... 82 
 

3.2.2.7 Cancer .................................................... 83 
 

3.2.3 Dermal Exposure .................................................... 86 
 

3.2.3.1 Death ..................................................... 86 
 

3.2.3.2 Systemic Effects ............................................ 86 
 

3.2.3.3 Immunological and Lymphoreticular Effects ...................... 87 
 

3.2.3.4 Neurological Effects ......................................... 87 
 

3.2.3.5 Reproductive Effects ......................................... 87 
 

3.2.3.6 Developmental Effects ....................................... 87 
 

3.2.3.7 Cancer .................................................... 87 
 

3.3 GENOTOXIC EFFECTS ..................................................... 87 
 

3.4 TOXICOKINETICS ......................................................... 94 
 

3.4.1 Absorption ......................................................... 95 
 

3.4.1.1 Inhalation Exposure .......................................... 95 
 

3.4.1.2 Oral Exposure .............................................. 96 
 

3.4.1.3 Dermal Exposure ............................................ 97 
 

3.4.2 	 Distribution ........................................................ 98 
 

3.4.2.1 Inhalation Exposure .......................................... 98 
 

3.4.2.2 Oral Exposure .............................................. 99 
 

3.4.2.3 Dermal Exposure ........................................... 100 
 

3.4.2.4 Other Routes of Exposure .................................... 100 
 

3.4.3 	 Metabolism ........................................................ 101 
 

3.4.3.1 Inhalation Exposure ......................................... 103 
 

3.4.3.2 Oral Exposure ............................................. 103 
 

3.4.3.3 Intraperitoneal Exposure ..................................... 104 
 

3.4.3.4 Other Routes of Exposure .................................... 104 
 

3.4.4 	 Elimination and Excretion ............................................ 105 
 

3.4.4.1 Inhalation Exposure ......................................... 105 
 

3.4.4.2 Oral Exposure ............................................. 106 
 

3.4.4.3 Dermal Exposure ........................................... 107 
 

3.4.4.4 Other Routes of Exposure .................................... 108 
 

3.4.5	 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) 

Models ........................................................... 108 
 

3.5 MECHANISMS OF ACTION ................................................ 111 
 

3.5.1 	 Pharmacokinetic Mechanisms ......................................... 111 
 

3.5.2 	 Mechanisms of Toxicity .............................................. 112 
 

3.5.3 	 Animal-to-Human Extrapolations ...................................... 113 
 

3.6 ENDOCRINE DISRUPTION ................................................ 114 
 

3.7 CHILDREN’S SUSCEPTIBILITY ............................................ 114 
 

3.8 BIOMARKERS OF EXPOSURE AND EFFECT ................................. 119 
 

3.8.1 Biomarkers Used to Identify or Quantify Exposure to 1,2-Dichloroethane ....... 120 
 

3.8.2 Biomarkers Used to Characterize Effects Caused by 1,2-Dichloroethane ........ 121 
 

3.9 INTERACTIONS WITH OTHER CHEMICALS ................................. 122 
 

3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE ...................... 125 
 

3.11 METHODS FOR REDUCING TOXIC EFFECTS ................................ 126 
 

3.11.1 Reducing Peak Absorption Following Exposure ........................... 127 
 
1,2-DICHLOROETHANE xv 

3.11.2 Reducing Body Burden .............................................. 127 
 

3.11.3 Interfering with the Mechanism of Action for Toxic Effects .................. 128 
 

3.12 ADEQUACY OF THE DATABASE ........................................... 129 
 

3.12.1 Existing Information on Health Effects of 1,2-Dichloroethane ................ 129 
 

3.12.2 Identification of Data Needs .......................................... 131 
 

3.12.3 Ongoing Studies .................................................... 151 
 

4. CHEMICAL AND PHYSICAL INFORMATION ...................................... 153 
 

4.1 CHEMICAL IDENTITY .................................................... 153 
 

4.2 PHYSICAL AND CHEMICAL PROPERTIES ................................... 153 
 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL ............................ 157 
 

5.1 PRODUCTION ........................................................... 157 
 

5.2 IMPORT/EXPORT ........................................................ 157 
 

5.3 USE ..................................................................... 160 
 

5.4 DISPOSAL ............................................................... 160 
 

6. POTENTIAL FOR HUMAN EXPOSURE ........................................... 161 
 

6.1 OVERVIEW .............................................................. 161 
 

6.2 RELEASES TO THE ENVIRONMENT ........................................ 163 
 

6.2.1 Air .............................................................. 163 
 

6.2.2 Water ............................................................ 163 
 

6.2.3 Soil .............................................................. 166 
 

6.3 ENVIRONMENTAL FATE .................................................. 166 
 

6.3.1 Transport and Partitioning ............................................ 166 
 

6.3.2 Transformation and Degradation ....................................... 168 
 

6.3.2.1 Air ...................................................... 168 
 

6.3.2.2 Water .................................................... 168 
 

6.3.2.3 Sediment and Soil .......................................... 169 
 

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT ............... 170 
 

6.4.1 Air .............................................................. 170 
 

6.4.2 Water ............................................................ 172 
 

6.4.3 Sediment and Soil .................................................. 174 
 

6.4.4 Other Environmental Media ........................................... 174 
 

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE .................. 175 
 

6.6 EXPOSURES OF CHILDREN ............................................... 178 
 

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES ...................... 179 
 

6.8 ADEQUACY OF THE DATABASE ........................................... 179 
 

6.8.1 Identification of Data Needs .......................................... 180 
 

6.8.2 Ongoing Studies .................................................... 183 
 

7. ANALYTICAL METHODS ....................................................... 185 
 

7.1 BIOLOGICAL MATERIALS ................................................ 185 
 

7.2 ENVIRONMENTAL SAMPLES .............................................. 187 
 

7.3 ADEQUACY OF THE DATABASE ........................................... 192 
 

7.3.1 Identification of Data Needs .......................................... 193 
 

7.3.2 Ongoing Studies .................................................... 193 
 

8. REGULATIONS AND ADVISORIES .............................................. 195 
 

9. REFERENCES ................................................................. 201 
 
1,2-DICHLOROETHANE xvi 

10. GLOSSARY .................................................................. 247 
 

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 
 
1,2-DICHLOROETHANE xvii 

LIST OF FIGURES 

3-1. Levels of Significant Exposure to 1,2-Dichloroethane - Inhalation ........................ 33 
 

3-2. Levels of Significant Exposure to 1,2-Dichloroethane - Oral ............................. 67 
 

3-3. Proposed Pathways for 1,2-Dichloroethane Metabolism ................................ 102 
 

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

Hypothetical Chemical Substance ................................................ 110 
 

3-5. Existing Information on Health Effects of 1,2-Dichloroethane ........................... 130 
 

6-1. Frequency of NPL Sites with 1,2-Dichloroethane Contamination ........................ 162 
 

1,2-DICHLOROETHANE xix 

LIST OF TABLES 

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

3-2. Levels of Significant Exposure to 1,2-Dichloroethane - Oral ............................. 51 
 

3-3. Genotoxicity of 1,2-Dichloroethane In Vivo .......................................... 89 
 

3-4. Genotoxicity of 1,2-Dichloroethane In Vitro ......................................... 92 
 

4-1. Chemical Identity of 1,2-Dichloroethane ........................................... 154 
 

4-2. Physical and Chemical Properties of 1,2-Dichloroethane .............................. 155 
 

5-1. United States Production of 1,2-Dichloroethane ...................................... 158 
 

5-2. Facilities that Produce, Process, or Use 1,2-Dichloroethane ............................. 159 
 

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

1,2-Dichloroethane ............................................................ 164 
 

6-2. Estimated Population Exposure to 1,2-Dichloroethane Through Releases to Ambient Air From a
 

Number of Specific Emission Sources ............................................. 177 
 

7-1. Analytical Methods for Determining 1,2-Dichloroethane in Biological Samples ............. 186 
 

7-2. Analytical Methods for Determining 1,2-Dichloroethane in Environmental Samples ......... 188 
 

8-1. Regulations and Guidelines Applicable to 1,2-Dichloroethane ........................... 196 
 

1,2-DICHLOROETHANE 1 

1. PUBLIC HEALTH STATEMENT
 

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

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

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

long-term federal cleanup activities. 1,2-Dichloroethane has been found in at least 570 of the 

1,585 current or former NPL sites. However, the total number of NPL sites evaluated for 

1,2-dichloroethane is not known. As more sites are evaluated, the sites at which 

1,2-dichloroethane is found may increase. This information is important because exposure to 

1,2-dichloroethane may harm you and because these sites may be sources of exposure. 

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

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

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

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

If you are exposed to 1,2-dichloroethane, many factors determine whether you’ll be harmed. 

These factors include the dose (how much), the duration (how long), and how you come in 

contact with it. You must also consider the other chemicals you’re exposed to and your age, sex, 

diet, family traits, lifestyle, and state of health. 

1.1 WHAT IS 1,2-DICHLOROETHANE? 

1,2-Dichloroethane is a clear, manufactured liquid that is not found naturally in the environment. 

It evaporates quickly at room temperature and has a pleasant smell and a sweet taste. 

1,2-Dichloroethane burns with a smoky flame. At this time, the most common use of 

1,2-dichloroethane is to make vinyl chloride, which is used to make a variety of plastic and vinyl 

products including polyvinyl chloride (PVC) pipes and other important construction materials, 

packaging materials, furniture and automobile upholstery, wall coverings, housewares, and 

automobile parts. 1,2-Dichloroethane is also used as a solvent and is added to leaded gasoline to 
1,2-DICHLOROETHANE 2 

1. PUBLIC HEALTH STATEMENT 

remove lead. In the past, it was also found in small amounts in products that industries used to 

clean cloth, remove grease from metal, and break down oils, fats, waxes, resins, and rubber. In 

the household, 1,2-dichloroethane was formerly a component of some cleaning solutions and 

pesticides; some adhesives, such as those used to glue wallpaper or carpeting; and some paint, 

varnish, and finish removers. Although large amounts of 1,2-dichloroethane are produced today, 

most is used to make other chemical products. 

Small amounts of 1,2-dichloroethane that were released into water or soil evaporate into the air. 

1,2-Dichloroethane that remains in soil from a spill or improper disposal can travel through the 

ground into water. The chemical may remain in water or soil for more than 40 days. 

Chapter 4 contains more chemical and physical information about 1,2-dichloroethane. 

Chapter 5 has more information on its uses, and Chapter 6 tells about its presence in the 

environment. 

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

ENVIRONMENT? 

1,2-Dichloroethane can enter the environment when it is made, packaged, shipped, or used. 

Most 1,2-dichloroethane is released to the air, although some is released to rivers or lakes. 

1,2-Dichloroethane could also enter soil, water, or air in large amounts in an accidental spill. 

1,2-Dichloroethane evaporates into the air very fast from soil and water. In the air, it breaks 

down by reacting with other compounds formed by the sunlight. 1,2-Dichloroethane will stay in 

the air for more than 5 months before it is broken down. It may also be removed from air in rain 

or snow. Since it stays in the air for a while, the wind may carry it over large distances. 

In water, 1,2-dichloroethane breaks down very slowly and most of it will evaporate to the air. 

Only very small amounts are taken up by plants and fish. We do not know exactly how long 

1,2-dichloroethane remains in water, but we do know that it remains longer in lakes than in 

rivers. 
1,2-DICHLOROETHANE 3 

1. PUBLIC HEALTH STATEMENT 

In soil, 1,2-dichloroethane either evaporates into the air or travels down through soil and enters 

underground water. Small organisms living in soil and groundwater may transform it into other 

less harmful compounds, although this happens slowly. If a large amount of 1,2-dichloroethane 

enters soil from an accident, hazardous waste site, or landfill, it may travel a long way 

underground and contaminate drinking water wells. 

More information on what happens to 1,2-dichloroethane in the environment can be found in 

Chapters 5 and 6. 

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

Humans are exposed to 1,2-dichloroethane mainly by breathing air or drinking water that 

contains 1,2-dichloroethane. Human exposure usually happens where the chemical has been 

improperly disposed of, or spilled onto the ground. However, low levels of 1,2-dichloroethane 

have also been found in the air near industries where it is made or used in manufacturing. 

Humans can be exposed to low levels of 1,2-dichloroethane through the skin or air by contact 

with old products made with 1,2-dichloroethane, such as cleaning agents, pesticides, and 

adhesives used to glue wallpaper and carpets. Such exposure is probably not enough to cause 

harmful health effects. 

1,2-Dichloroethane has been found in U.S. drinking water at levels ranging from 0.05 to 64 parts 

of 1,2-dichloroethane per billion (ppb) parts of water. An average amount of 175 ppb has been 

found in 12% of the surface water and groundwater samples taken at 2,783 hazardous wastes 

sites. 1,2-Dichloroethane has also been found in the air near urban areas at levels of 

0.10–1.50 ppb and near hazardous waste sites at levels of 0.01–0.003 ppb. Small amounts of 

1,2-dichloroethane have also been found in foods. 

Humans may also be exposed to 1,2-dichloroethane through its use as a gasoline additive to 

reduce lead content, but these small levels are not expected to affect human health. This is 

probably not an important way that people are exposed to 1,2-dichloroethane in the United 

States, since leaded gasolines are rarely used today. 
1,2-DICHLOROETHANE 4 

1. PUBLIC HEALTH STATEMENT 

Additional information on levels in the environment and potential for human exposure are 

presented in Chapter 6. 

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

1,2-Dichloroethane can enter the body when people breathe air or drink water that contains 

1,2-dichloroethane. Studies in animals also show that 1,2-dichloroethane can enter the body 

through the skin. Humans are most likely to be exposed at work and outside the workplace by 

drinking water that contains 1,2-dichloroethane, or by breathing 1,2-dichloroethane that has 

escaped from contaminated water or soil into the air. 

Experiments in animals show that 1,2-dichloroethane that is breathed in or swallowed goes to 

many organs of the body, but usually leaves in the breath within 1 or 2 days. The breakdown 

products of 1,2-dichloroethane in the body leave quickly in the urine. Soil near hazardous waste 

sites probably does not have high amounts of 1,2-dichloroethane because it evaporates quickly 

into the air. This suggests that exposure near a hazardous waste site would most likely occur by 

breathing contaminated air rather than by touching contaminated soil. 

Further information on how 1,2-dichloroethane can enter and leave the body is presented in 

Chapter 3. 

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

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

who have been harmed, scientists use many tests. 

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

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

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

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

to protect public health. Scientists have the responsibility to treat research animals with care and 
1,2-DICHLOROETHANE 5 

1. PUBLIC HEALTH STATEMENT 

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

with strict animal care guidelines. 

People who were accidentally exposed to large amounts of 1,2-dichloroethane in the air or who 

swallowed 1,2-dichloroethane by accident or on purpose often developed nervous system 

disorders and liver and kidney disease. Lung effects were also seen after a large amount of 

1,2-dichloroethane was inhaled. People often died from heart failure. We do not know what 

levels of 1,2-dichloroethane caused these effects, but they are probably high. Studies in 

laboratory animals also found that breathing or swallowing large amounts of 1,2-dichloroethane 

produced nervous system disorders, kidney disease, or lung effects. Reduced ability to fight 

infection was also seen in laboratory animals who breathed or swallowed 1,2-dichloroethane, but 

we do not know if this also occurs in humans. Longer-term exposure to lower doses also caused 

kidney disease in animals. 

So far, exposure to 1,2-dichloroethane has not been associated with cancer in humans. One 

study showed a relationship between increased cancer and exposure to pollutants in 

groundwater, including 1,2-dichloroethane, but the people were probably exposed to many other 

chemicals at the same time. Cancer was found in laboratory animals who were fed large doses 

of 1,2-dichloroethane. When 1,2-dichloroethane was put on the skin of laboratory animals, they 

developed lung tumors. We are not sure whether breathing 1,2-dichloroethane causes cancer in 

animals. Because of the cancer findings in animals, the possibility of cancer in humans cannot 

be ruled out. The Department of Health and Human Services (DHHS) has determined that 

1,2-dichloroethane may reasonably be expected to cause cancer. The International Agency for 

Research on Cancer (IARC) has determined that 1,2-dichloroethane can possibly cause cancer in 

humans. EPA has determined that 1,2-dichloroethane is a probable human carcinogen. 

Additional information regarding the health effects of 1,2-dichloroethane can be found in 

Chapter 3. 
1,2-DICHLOROETHANE 6 

1. PUBLIC HEALTH STATEMENT 

1.6 HOW CAN 1,2-DICHLOROETHANE AFFECT CHILDREN? 

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

to maturity at 18 years of age in humans. 

Children can be exposed to 1,2-dichloroethane by breathing contaminated air, and possibly by 

drinking contaminated water. In the past, 1,2-dichloroethane had been used in certain household 

items, such as cleaning products and adhesives, but is no longer used in these products. There is 

a possibility that using of one of these older household products containing 1,2-dichloroethane to 

clean floors or glue carpets could result in exposure, since children often crawl on floors and 

play on carpets. Such exposures would probably last a few days or less, since 1,2-dichloroethane 

evaporates very quickly. Children are not likely to be exposed to 1,2-dichloroethane from 

parents’ clothing or other items removed from the workplace. Because 1,2-dichloroethane has 

been detected in human milk, it is possible that young children could be exposed to 1,2-dichloroethane from breast-feeding mothers who had been exposed to sources of 1,2-dichloroethane. 

There have been no studies of health effects in children exposed to 1,2-dichloroethane, and we 

have no reliable information on whether 1,2-dichloroethane causes birth defects in children. One 

study broadly suggests that heart problems could occur in the human fetus from mothers being 

exposed to 1,2-dichloroethane along with some other chemicals, but the information is not 

reliable enough for us to be sure whether 1,2-dichloroethane is responsible for the defects. 

Studies of pregnant laboratory animals indicate that it probably does not produce birth defects or 

affect reproduction. We do know, however, that when the pregnant animal is exposed to 

1,2-dichloroethane, the fetus is probably also exposed. 

It is likely that children exposed to 1,2-dichloroethane after birth would show the same health 

effects that are expected to occur in adults, especially liver and kidney disease. There is no 

information to determine whether children differ from adults in their sensitivity to the health 

effects of 1,2-dichloroethane. 
1,2-DICHLOROETHANE 7 

1. PUBLIC HEALTH STATEMENT 

More information regarding children’s health and 1,2-dichloroethane can be found in 

Section 3.7. 

1.7	 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO 

1,2-DICHLOROETHANE? 

If your doctor finds that you have been exposed to significant amounts of 1,2-dichloroethane, ask 

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

department to investigate. 

In the past, 1,2-dichloroethane was used in small amounts in household products such as 

cleaning agents, pesticides, and wallpaper and carpet glue. It is possible that you may have old 

containers of such products in your home. Risk of exposure from this source could be eliminated 

if these older products were immediately discarded. Otherwise, household chemicals should be 

stored out of reach of young children to prevent accidental poisonings. Always store household 

chemicals in their original labeled containers. Never store household chemicals in containers 

that children would find attractive to eat or drink from, such as old soda bottles. Keep your 

Poison Control Center’s number next to the phone. Sometimes older children sniff household 

chemicals in an attempt to get high. Your children may be exposed to 1,2-dichloroethane by 

inhaling products containing it. Talk with your children about the dangers of sniffing chemicals. 

The exposure of your family to 1,2-dichloroethane can be reduced by throwing away any 

household products that contain it. You may wish to contact your county health department for 

appropriate disposal methods. 

1,2-Dichloroethane has been found in drinking water in the United States. Most of the time, 

1,2-dichloroethane has been found in small amounts that do not pose a major health risk. You 

may want to contact your water supplier or local health department to get information about the 

levels of 1,2-dichloroethane in the drinking water. 
1,2-DICHLOROETHANE 8 

1. PUBLIC HEALTH STATEMENT 

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

EXPOSED TO 1,2-DICHLOROETHANE? 

1,2-Dichloroethane has been found in the breath, blood, breast milk, and urine of exposed 

people. Because breath samples are easily collected, testing breathed-out or exhaled air is now a 

possible way to find out whether someone has recently been exposed to 1,2-dichloroethane. 

However, tests that measure small amounts in human breath, tissues, and fluids may not be 

available at your doctor's office because they require special equipment. Your physician can 

refer you to a facility where these tests are done. Although these tests can show that you have 

been exposed to 1,2-dichloroethane, it is not possible to tell if you will experience any harmful 

health effects. Because 1,2-dichloroethane leaves the body fairly quickly, these methods are best 

for finding exposures that occurred within the last several days. Exposure to 1,2-dichloroethane 

at hazardous waste sites will probably include exposure to other organic compounds at the same 

time. Therefore, levels of 1,2-dichloroethane measured in the body by these methods may not 

show exposure to 1,2-dichloroethane only. Medical tests available at a doctor's office include 

lung-, liver-, and kidney-function tests, but these tests look for damage that has already occurred 

from general chemical exposure and do not determine the cause of damage. Damage could also 

be the result of lifestyle (e.g., drinking alcohol, smoking) or general exposure to environmental 

agents. Other methods to measure the effects of exposure to 1,2-dichloroethane (such as 

abnormal enzyme levels) do not measure the effects of exposure to 1,2-dichloroethane only, but 

measure effects of other chemicals as well. 

1.9	 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO 

PROTECT HUMAN HEALTH? 

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

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

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

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

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

law. Federal organizations that develop recommendations for toxic substances include the 
1,2-DICHLOROETHANE 9 

1. PUBLIC HEALTH STATEMENT 

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

Occupational Safety and Health (NIOSH). 

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

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

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

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

studies, or other factors. 

Recommendations and regulations are also periodically updated as more information becomes 

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

provides it. Some regulations and recommendations for 1,2-dichloroethane include the 

following: 

The federal government has developed regulatory standards and guidelines to protect people 

from the possible health effects of 1,2-dichloroethane in air. OSHA has set a limit of 50 parts of 

1,2-dichloroethane per million parts of air (ppm, 1 ppm is 1,000 times more than 1 ppb) in the 

workplace for an 8-hour day, 40-hour week. NIOSH recommends that a person not be exposed 

daily in the workplace to more than 1 ppm 1,2-dichloroethane for a 10-hour day, 40-hour week. 

NIOSH calls 1,2-dichloroethane a possible occupational carcinogen. EPA also calls the 

compound a probable human cancer-causing agent, based on experiments in animals. 

The federal government has also set regulatory standards and guidelines to protect people from 

the possible health effects of 1,2-dichloroethane in drinking water. EPA has set a limit in water 

of 0.005 milligrams of 1,2-dichloroethane per liter (5 ppb). 
1,2-DICHLOROETHANE 10 

1. PUBLIC HEALTH STATEMENT 

1.10 WHERE CAN I GET MORE INFORMATION? 

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

environmental quality department or 

Agency for Toxic Substances and Disease Registry
 

Division of Toxicology
 

1600 Clifton Road NE, Mailstop E-29
 

Atlanta, GA 30333
 

* Information line and technical assistance 

Phone: 1-888-42-ATSDR (1-888-422-8737) or (404) 639-6357
 

Fax: (404) 639-6359
 

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

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

hazardous substances. 

* To order toxicological profiles, contact 

National Technical Information Service
 

5285 Port Royal Road
 

Springfield, VA 22161
 

Phone: (800) 553-6847 or (703) 605-6000
 
1,2-DICHLOROETHANE 11 

2. RELEVANCE TO PUBLIC HEALTH
 

2.1	 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO 1,2-DICHLOROETHANE IN 

THE UNITED STATES 

1,2-Dichloroethane, also called ethylene dichloride, is a volatile, clear, manufactured liquid that is not 

found naturally in the environment. It has a pleasant smell and a sweet taste and burns with a smoky 

flame. 1,2-Dichloroethane is readily soluble in water and several organic solvents such as alcohol, 

chloroform, and ether. 1,2-Dichloroethane is one of the most widely produced chemicals in the world. 

Its predominant use is in the manufacture of vinyl chloride. 1,2-Dichloroethane was formerly used in 

varnish and finish removers, soaps and scouring compounds, organic synthesis for extraction and cleaning 

purposes, metal degreasers, ore flotation, and paints, coatings, and adhesives. 

1,2-Dichloroethane is a widespread contaminant released to the environment during its production and 

use, with the vast majority of the fugitive emissions going into the air. Vapor-phase 1,2-dichloroethane is 

photochemically degraded in the atmosphere with an estimated reaction half-life of about 73 days. If 

released to soil, 1,2-dichloroethane is not expected to adsorb strongly and may leach into groundwater. 

Volatilization is expected to be an important environmental fate process for 1,2-dichloroethane in soil and 

bodies of water. Biodegradation is expected to occur slowly in both water and soil surfaces. Hydrolysis 

and photolysis are not expected to be important fate processes, and the potential for bioconcentration in 

aquatic organisms appears to be low. 

The general population is exposed to 1,2-dichloroethane primarily from inhalation of ambient air, 

particularly near point sources. Other potential routes of exposure for the general population include 

ingestion of 1,2-dichloroethane in contaminated drinking water or food items and dermal absorption. In 

addition, inhalation exposure may occur from 1,2-dichloroethane that has volatilized from water during 

activities such as cooking, bathing, showering, and dishwashing, if 1,2-dichloroethane is in the water 

supply. Occupational exposure to 1,2-dichloroethane occurs through inhalation and dermal contact with 

the compound at workplaces where it is produced or used. Children are expected to be exposed to 

1,2-dichloroethane by the same routes as adults. 1,2-Dichloroethane has been detected in human milk, 

indicating that infants could possibly be exposed to 1,2-dichloroethane from breast-feeding mothers. The 

importance of this route of child exposure is unclear because current data on the concentration of 

1,2-dichloroethane in breast milk are not available. 
1,2-DICHLOROETHANE 12 

2. RELEVANCE TO PUBLIC HEALTH 

Median daily atmospheric concentrations of 1,2-dichloroethane are typically in the 0.01–0.1 ppb range for 

urban, suburban, rural, and remote sites, and slightly higher near point sources such as factories, treatment 

plants, and hazardous waste sites. The estimated daily intake of 1,2-dichloroethane in Japan attributed to 

food ingestion is 0.004 mg/day, a level well below ATSDR’s intermediate oral MRL of 0.2 mg/kg/day for 

1,2-dichloroethane. Since the levels of 1,2-dichloroethane in food products of Japan are similar to those 

in the United States, the daily intake value may also be similar. 

Populations residing near hazardous waste disposal sites or municipal landfills may be subject to higher 

than average levels of 1,2-dichloroethane in ambient air and drinking water since 1,2-dichloroethane is 

volatile and is mobile in soil and may leach into drinking water supplies. 1,2-Dichloroethane is included 

in the priority list of hazardous substances identified by ATSDR and the Environmental Protection 

Agency (EPA), and has been found in at least 570 of the 1,585 current or former National Priorities List 

(NPL) sites. However, the total number of NPL sites evaluated for 1,2-dichloroethane is not known. As 

more sites are evaluated, the sites at which 1,2-dichloroethane is found may increase. 

2.2 SUMMARY OF HEALTH EFFECTS 

Short-, intermediate-, and long-term health effects can result from inhalation or ingestion of, or dermal 

contact to, 1,2-dichloroethane. Main targets of mammalian toxicity include the liver, kidneys, and 

neurological, cardiovascular, and immune systems. A limited amount of information is available 

regarding effects in humans, most coming from case reports of people who died following acute exposure 

to high levels by inhalation or ingestion. Symptoms and signs in these people included central nervous 

system depression, nausea and vomiting, corneal opacity, bronchitis, respiratory distress, lung congestion, 

myocardial lesions, hemorrhagic gastritis and colitis, increased blood clotting time, hepatocellular 

damage, renal necrosis, and histopathological changes in brain tissue. Death was most often attributed to 

cardiac arrhythmia. Inhalation and oral studies in animals have found similar effects, as well as 

immunological, genotoxic, and carcinogenic effects not reported in humans. Animal data further indicate 

that 1,2-dichloroethane is unlikely to cause reproductive or developmental toxicity at doses below those 

that are maternally toxic. 

Route-related differences in some toxic and carcinogenic responses have been observed between gavage 

and drinking water or inhalation exposure in animal studies of 1,2-dichloroethane. The differences in 

response may be due to saturation of the detoxification/excretion mechanism due to bolus gavage dosing. 

As discussed in Chapter 3 (Section 3.5, Mechanisms of Action), effects of 1,2-dichloroethane in various 
 

 

1,2-DICHLOROETHANE 13 

2. RELEVANCE TO PUBLIC HEALTH 

tissues appear to be largely mediated by reactive intermediates formed by conjugation with glutathione. 

The reaction of 1,2-dichloroethane and glutathione is unusual in that it results in activation rather than 

detoxification (i.e., the typical consequence of conjugation of xenobiotics with glutathione). Toxicity 

may occur when the biotransformation processes are saturated, thereby allowing higher levels of 

1,2-dichloroethane to circulate throughout the body and conjugate with glutathione instead of being 

detoxified and eliminated. Therefore, even though certain health effects might be expected in humans 

ingesting sufficient doses of 1,2-dichloroethane, it is uncertain whether the effects would occur following 

typical drinking water and inhalation exposures. 

Hepatic Effects. Liver effects have been observed in cases of humans who died following acute 

inhalation or ingestion of 1,2-dichloroethane. Hepatotoxicity was indicated by an increase in levels of 

serum markers of liver dysfunction, an enlarged liver, and extensive centrilobular necrosis in a man who 

was exposed to concentrated 1,2-dichloroethane vapors for 30 minutes and subsequently died. Necrosis 

and cirrhosis were reported in people following acute high-level oral exposure to $570 mg/kg/day. 

Evidence from animal studies supports the conclusion that the liver is a target organ for 1,2-dichloroethane. Hepatic effects in exposed animals were not limited to any specific route or duration of exposure 

and included increased levels of serum markers of liver dysfunction, increased liver weight, and fatty 

degeneration. For inhalation exposure, the lowest concentrations producing hepatic effects were 400 ppm 

for acute-duration exposure and 100 ppm for intermediate-duration exposure. As discussed in 

Section 2.3, liver histopathology is the basis of the chronic-duration minimal risk level (MRL) for 

inhalation oral exposure. For oral exposure, the lowest dose producing hepatic effects was 18 mg/kg/day 

for intermediate-duration exposure. 

Renal Effects. 1,2-Dichloroethane is acutely nephrotoxic in humans following both inhalation and 

ingestion. Renal effects observed in individuals who died following acute high-level exposure were 

diffuse necrosis, tubular necrosis, and kidney failure. Renal effects seen in experimental animals include 

increased kidney weight, cloudy swelling of the tubular epithelium, tubular degeneration and 

regeneration, karyomegaly, dilatation, protein casts, and mineralization. The effects in animals were not 

limited to any specific route or duration of exposure and support the conclusion that the kidney is a target 

organ for 1,2-dichloroethane. For inhalation exposure, the lowest concentration reported to produce renal 

effects was 400 ppm for durations of 8–12 days and 8 months. For oral exposure, the lowest dose 

producing renal effects was 58 mg/kg/day for 13 weeks. Increased kidney weight, considered to be an 

early-stage adverse effect because it leads to histopathological changes at higher doses, was used to derive 

the intermediate-duration MRL for oral exposure to 1,2-dichloroethane as discussed in Section 2.3. 
 

 

1,2-DICHLOROETHANE 14 

2. RELEVANCE TO PUBLIC HEALTH 

Immunological and Lymphoreticular Effects. Immunological effects have not been reported in 

humans exposed to 1,2-dichloroethane. In mice, however, this chemical had immunosuppressive effects 

following both acute inhalation exposure and acute oral exposure. A single 3-hour inhalation exposure to 

5–11 ppm increased susceptibility of mice to bacterial infection, although no changes in bactericidal 

activity or other immune function end points were found in rats after a single 5-hour exposure to 200 ppm 

or 12 5-hour exposures to 100 ppm. Effects observed in mice following gavage administration of 4.9 or 

49 mg/kg/day for 14 days included reduced humoral immunity (immunoglobulin response to sheep red 

blood cells) and cell-mediated immunity (delayed-type hypersensitivity response to sheep erythrocytes). 

The immune system was the most sensitive target for short-term exposure to 1,2-dichloroethane by both 

the inhalation and oral routes in mice. Because of the apparent interspecies differences in 

immunotoxicity; however, it is unclear whether the immune system could be a target of 1,2-dichloroethane in humans following acute exposure by inhalation or ingestion. 

Immune function has not been evaluated in intermediate- or chronic-duration inhalation studies of 

1,2-dichloroethane. Immune function also has not been evaluated after chronic oral exposure, although 

mice given up to 189 mg/kg/day of 1,2-dichloroethane in drinking water for 90 days had no treatmentrelated effects on either the antibody-forming cell response or the delayed-type hypersensitivity response 

after immunization with sheep erythrocyte antigens. Leucocyte counts were not affected in intermediateduration drinking water and gavage studies in rats, and intermediate and chronic oral exposures did not 

produce histological changes in immune system tissues in rats and mice. Although immunological effects 

might be expected in humans ingesting sufficient doses of undiluted 1,2-dichloroethane, it is uncertain 

whether the effects would occur in people exposed via drinking water from wells located near hazardous 

waste sites. 

Neurological Effects. Neurological symptoms and signs in people acutely exposed to high levels of 

1,2-dichloroethane by inhalation or ingestion included headache, irritability, drowsiness, tremors, partial 

paralysis, and coma. Autopsies of people who died revealed effects in the brain including hyperemia, 

hemorrhage, myelin degeneration, diffuse changes in the cerebellum, shrunken appearance and pyknotic 

nuclei in the Purkinje cell layer of the cerebellum, and parenchymous changes in the brain and spinal 

cord. 

The results of animal inhalation studies confirm that the central nervous system is a target of high 

concentrations of 1,2-dichloroethane. Symptoms similar to those reported in humans, such as tremors, 

abnormal posture, uncertain gait, and narcosis were observed after high-level acute vapor exposures. In 
 

 

1,2-DICHLOROETHANE 15 

2. RELEVANCE TO PUBLIC HEALTH 

addition, clinical signs of neurotoxicity and mild necrosis in the cerebellum were found in rats 

administered 240–300 mg/kg/day of 1,2-dichloroethane by gavage for 13 weeks. In contrast, no clinical 

signs or neurological lesions were seen in rats exposed through their drinking water up to 492 mg/kg/day 

or mice exposed up to 4,210 mg/kg/day for 13 weeks, and no brain lesions were seen in rats intermittently 

exposed to 50 ppm for 2 years. The effects seen in the gavage study at a level lower than the NOAEL in 

the drinking water study might be attributable to the method of dosing. These data do not sufficiently 

characterize the potential for 1,2-dichloroethane to induce more subtle neurotoxic effects following lowlevel prolonged exposure by inhalation, oral, or dermal exposure. Acute exposure levels high enough to 

produce neurological effects would not be expected to occur at hazardous waste sites or in the workplace, 

but might result from accidental occupational exposure or accidental or intentional ingestion. 

Cardiovascular Effects. Cardiac arrhythmia was given as the cause of death of a man briefly 

exposed to 1,2-dichloroethane as a concentrated vapor. Autopsy revealed diffuse degenerative changes in 

the myocardium (fragmentation, interstitial edema, loss of nuclei from myocardial fibers). In addition, 

cardiovascular insufficiency and hemorrhage were major factors contributing to death in people following 

acute high-level oral exposure to $570 mg/kg/day. In laboratory animals, myocardial inflammation was 

reported following acute inhalation of lethal concentrations, and fatty infiltration of the myocardium was 

observed in guinea pigs that died following exposure to 200 ppm for 25 weeks and in monkeys that 

survived the same exposure regimen. These findings in animals were based upon a very limited number 

of observations and in some cases did not include comparison to controls. More complete animal studies 

did not report cardiovascular histopathologic effects following high-level intermediate-duration oral 

exposure or low-level chronic-duration inhalation exposure. Overall, the data suggest that the heart could 

be a target of 1,2-dichloroethane following acute high-level exposure and possibly longer-term inhalation 

exposure as well. Levels that might produce cardiovascular effects are not likely to be found at hazardous 

waste sites or a well-regulated workplace. 

Developmental Effects. The only studies regarding developmental effects in humans are 

epidemiologic investigations of adverse birth outcomes that found increased odds ratios for exposure to 

1,2-dichloroethane in public drinking water and major cardiac defects (but not neural tube defects), and 

for residence within the census tract of NPL sites contaminated with 1,2-dichloroethane and neural tube 

defects (but not heart defects). Primary routes of exposure in these epidemiologic studies may have been 

both oral and inhalation, including inhalation of 1,2-dichloroethane volatilized from household water. It 

has been previously shown that taking a 10-minute shower is equivalent to drinking 1–3 liters of the same 

water contaminated with some volatile organic compounds. In these studies, the study populations were 
 

1,2-DICHLOROETHANE 16 

2. RELEVANCE TO PUBLIC HEALTH 

also simultaneously exposed to elevated levels of other contaminants. Because of the mixed chemical 

exposure, lack of dose-response information, and inconsistency between the findings of the two studies, 

the associations with 1,2-dichloroethane are only suggestive and do not establish a cause-and-effect 

relationship. 

The weight of evidence from available inhalation and oral studies in rats, mice, and rabbits indicates that 

1,2-dichloroethane is not fetotoxic or teratogenic, although indications of embryolethality at maternally 

toxic doses have been reported. (There are reports of increased embryo and pup mortality following 

intermediate-duration inhalation of lower [not maternally toxic] concentrations of 1,2-dichloroethane, but 

the reliability of the results is uncertain due to the lack of statistical analysis and inadequate description of 

methods.) The possibility of induction of cardiac malformations in human offspring by 1,2-dichloroethane, as suggested by the epidemiologic data, was not confirmed in available animal studies because the 

teratology protocols did not include detailed examinations of dissected hearts. Studies of dichloroethylene and trichloroethylene, which are metabolized to some of the same reactive intermediates as 

1,2-dichloroethane, have also shown evidence of heart malformations in humans as well as animal cardiac 

teratogenicity. Overall, the available information does not indicate that 1,2-dichloroethane is a 

developmental toxicant in animals at doses below those that cause other toxic effects. 

Reproductive Effects. A single study on reproductive effects of exposure to 1,2-dichloroethane in 

humans is suggestive of a reduction in gestation duration, but co-exposure to other chemicals occurred in 

most cases, and the adequacy of the study design could not be evaluated because of reporting 

deficiencies. Results of animal studies indicate that 1,2-dichloroethane is unlikely to cause reproductive 

impairment at doses that are not maternally toxic. Some inhalation studies found that exposure of dams to 

1,2-dichloroethane prior to mating and continuing into gestation caused pre-implantation loss and 

embryolethality in rats, although the study methods were not well reported and the reliability of the data 

is uncertain. In contrast to these findings, a well-designed study of reproductive toxicity found no 

adverse effects on the fertility of rats exposed by inhalation to 10-fold higher concentrations of 

1,2-dichloroethane in a one-generation reproduction study. One- and two-generation reproduction studies 

found no chemical-related effects on fertility indices in long-term oral studies in mice and rats, but 

exposure to higher oral doses caused increases in nonsurviving implants and resorptions in rats that also 

experienced maternal toxicity. Histological examinations of the testes, ovaries, and other male and 

female reproductive system tissues were performed in intermediate- and chronic-duration inhalation and 

oral animal studies with negative results, but reproductive function was not evaluated in these studies. 

Although 1,2-dichloroethane appears to have induced embryotoxic effects in some animal studies, the 
 

1,2-DICHLOROETHANE 17 

2. RELEVANCE TO PUBLIC HEALTH 

overall indication of the data is that this chemical is unlikely to impair reproduction at doses that do not 

also cause other toxic manifestations. 

Cancer. Epidemiological studies that have investigated associations between occupational or oral 

exposure to 1,2-dichloroethane and increased incidences of cancer are inadequate for assessing 

carcinogenicity in humans, due to complicating co-exposures to various other chemicals. In animals, no 

tumors were produced in rats and mice exposed to 1,2-dichloroethane via inhalation. The inhalation data 

are limited by use of a single, subthreshold exposure level in one study, and exceedance of the maximum 

tolerated dose in rats, less-than-lifetime study duration, and poor survival in mice in the other study. 

1,2-Dichloroethane induced a clear positive carcinogenic response in animals after gavage administration, 

causing statistically significant increases in forestomach squamous cell carcinomas, hemangiosarcomas, 

and subcutaneous fibromas in male rats; mammary gland adenocarcinomas and hemangiosarcomas in 

female rats; hepatocellular carcinomas and alveolar/bronchiolar adenomas in male mice; and 

alveolar/bronchiolar adenomas, mammary carcinomas, and endometrial tumors in female mice. Other 

animal bioassays provide supportive or suggestive evidence for the carcinogenicity of 1,2-dichloroethane. 

One study showed compound-related lung papillomas following lifetime dermal exposure of female mice. 

Two additional studies found that pulmonary adenomas were induced in mice by intraperitoneal injection. 

The positive and suggestive carcinogenicity results from animal bioassays, along with data indicating that 

1,2-dichloroethane and some metabolites are mutagenic and capable of forming DNA adducts (see 

Chapter 3, Section 3.3), provide sufficient evidence to suggest that 1,2-dichloroethane is a probable 

human carcinogen. Because oral, dermal, and intraperitoneal exposure of experimental animals to 

1,2-dichloroethane is associated with the induction of tumors remote from the site of administration, 

1,2-dichloroethane should be considered potentially carcinogenic by the inhalation route of exposure as 

well. The Department of Health and Human Services (DHHS) has determined that 1,2-dichloroethane 

may reasonably be anticipated to be a human carcinogen. The International Agency Research on Cancer 

(IARC) has placed 1,2-dichloroethane in Group 2B (possibly carcinogenic to humans), and the EPA has 

classified 1,2-dichloroethane as a Group B2 carcinogen (probable human carcinogen). 
1,2-DICHLOROETHANE 18 

2. RELEVANCE TO PUBLIC HEALTH 

2.3 MINIMAL RISK LEVELS 

Inhalation MRLs 

An acute-duration inhalation MRL has not been derived for 1,2-dichloroethane. The lowest effect level 

for acute inhalation exposure is 5.4 ppm for significantly increased mortality in mice from streptococcal 

(Streptococcus zooepidemicus) bacterial challenge following a single 3-hour exposure to 

1,2-dichloroethane. Significantly increased mortality from streptococcal challenge in addition to 

decreased bactericidal activity after challenge with Klebsiella pneumoniae were seen in mice at 10.8 ppm. 

The no-observed-adverse-effect-level (NOAEL) for susceptibility to streptococcal challenge in mice was 

2.3 ppm after a single 3-hour exposure or five 3-hour exposures on consecutive days. In the same study, 

rats did not show decreased bactericidal activity from K. pneumoniae challenge following single 

exposures of up to 200 ppm, or multiple 5-hour exposures of up to 100 ppm of 1,2-dichloroethane. 

Sherwood et al. indicated that the clear interspecies difference in immunotoxic susceptibility suggests 

against extrapolating from animals to humans. The MRL Workgroup concluded that the massive 

streptococcal challenge to mice, consisting of whole-body, 30-minute exposures to aerosols of bacteria 

for an estimated challenge exposure of 2x104

 inhaled viable streptococci, is unlikely to be relevant to 

normal human immunological challenge and that, therefore, the increased mortality in mice observed in 

the Sherwood et al. study is not a suitable basis for an acute inhalation MRL. Immune function has not 

been evaluated in intermediate- or chronic-duration inhalation studies of 1,2-dichloroethane, although 

immunosuppressive effects have been reported in mice that were orally exposed to 1,2-dichloroethane for 

14 days. 

C	 An MRL of 0.6 ppm has been derived for chronic-duration inhalation exposure (>365 days) to 

1,2-dichloroethane. This chronic MRL is also expected to be protective for intermediateduration inhalation exposure (15–364 days). 

The MRL was derived by dividing a NOAEL of 50 ppm for liver histopathology in rats exposed for 

7 hours/day, 5 days/week for 2 years by an uncertainty factor of 90 (3 for interspecies extrapolation after 

dosimetric adjustment; 10 for human variability; and 3 as a modifying factor for database deficiencies). 

Although other concentrations of 1,2-dichloroethane were not tested, confidence in the NOAEL is high 

due to the group size (50 of each sex) and scope of the study. Additionally, the liver is a documented 

target of 1,2-dichloroethane toxicity in several acute- and intermediate-duration inhalation studies, as well 

as in a number of studies of orally exposed animals. Limitations in the acute and intermediate inhalation 

studies preclude considering them as the basis for MRL derivation, but the weight of evidence indicates 
19 

C

1,2-DICHLOROETHANE 

2. RELEVANCE TO PUBLIC HEALTH 

that NOAELs for hepatotoxicity in the intermediate-duration studies are higher than the chronic liver 

NOAEL. Consequently, the chronic-duration inhalation MRL of 0.6 ppm is also expected to be 

protective of toxic effects after intermediate-duration inhalation exposures to 1,2-dichloroethane. 

Oral MRLs 

An MRL has not been derived for acute-duration oral exposure (#14 days) to 1,2-dichloroethane. The 

lowest effect level that can be identified for acute oral toxicity is a lowest-observed-adverse-effect level 

(LOAEL) of 4.9 mg/kg/day for immunosuppression from a mouse study. Doses lower than 

4.9 mg/kg/day were not tested, precluding identification of a NOAEL. Male mice that were treated with 

4.9 or 49 mg/kg/day by gavage for 14 days showed a significant dose-related reduction in humoral 

immune response (IgM response to sheep erythrocytes). The number of antibody-forming cells (AFCs) 

was dose-related and statistically significantly reduced at both dose levels; when adjusted to AFC/106 

cells, there was an apparent negative trend with dose, but a significant reduction occurred only in the 

high-dose group. The cell-mediated immune response (delayed-type hypersensitivity response to sheep 

erythrocytes) was significantly reduced in both dose groups, but not in a dose-related manner. There was 

also a depression in leukocytes in the high dose group. However, because administration of 

1,2-dichloroethane in the drinking water at doses as high as 189 mg/kg/day for 90 days failed to induce 

immunosuppressive effects in mice, it was determined that it may not be appropriate to base an MRL on 

an effect level from a gavage oil study due to toxicokinetic considerations (e.g., possible bolus saturation 

of the detoxification/excretion mechanism). 

An MRL of 0.2 mg/kg/day was derived for intermediate-duration oral exposure (15–364 days) 

to 1,2-dichloroethane. 

This MRL was derived by dividing a LOAEL of 58 mg/kg/day for increased absolute and relative kidney 

weights in rats that were exposed to 1,2-dichloroethane in drinking water for 13 weeks by an uncertainty 

factor of 300 (3 for use of minimal LOAEL; 10 for interspecies extrapolation; and 10 for human 

variability). Doses lower than 58 mg/kg/day were not tested, precluding identification of a NOAEL. The 

increases in kidney weight were dose-related and were considered to be an early-stage adverse effect in a 

known target organ, because histopathological changes were manifested in the kidney at higher doses in 

the rats as well as in similarly exposed mice in the same study. Tissue examinations showed dose-related, 

increased incidences of minimal-to-moderate renal regeneration in rats at $102 mg/kg/day and mice at 

$249 mg/kg/day. These changes are indicative of previous tubular injury with subsequent repair. More 
1,2-DICHLOROETHANE 20 

2. RELEVANCE TO PUBLIC HEALTH 

severe kidney effects including karyomegaly, dilatation, protein casts, and mineralization occurred in 

male mice exposed to 4,210 mg/kg/day. Observations of increased relative kidney weight in rats that 

were treated with $75 or 90 mg/kg/day by gavage for 90 days are supportive of the 58 mg/kg/day 

LOAEL. 

An MRL has not been derived for chronic oral exposure ($365 days) to 1,2-dichloroethane, because an 

appropriate study was not identified. The only chronic oral study tested rats and mice that were treated by 

gavage 5 days/week for up to 78 weeks. This study had several limitations such as dosage adjustments, 

possible contamination by other chemicals tested in the same laboratory, poor survival, and small 

numbers of control animals. Additionally, it may not be appropriate, in this case, to base an MRL on an 

effect level from a gavage oil study due to toxicokinetic considerations (e.g., possible bolus saturation of 

the detoxification/excretion mechanism). 
1,2-DICHLOROETHANE 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 

1,2-dichloroethane. 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 

lowest-observed-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 

"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 
1,2-DICHLOROETHANE 22 

3. HEALTH EFFECTS 

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 1,2-dichloroethane are indicated in Tables 3-1 and 3-2 and Figures 3-1 and 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. 

Estimates of exposure levels posing minimal risk to humans (Minimal Risk Levels or MRLs) have been 

made for 1,2-dichloroethane. 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 

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. 
1,2-DICHLOROETHANE 23 

3. HEALTH EFFECTS 

A User's Guide has been provided at the end of this profile (see Appendix B). This guide should aid in 

the interpretation of the tables and figures for Levels of Significant Exposure and the MRLs. 

3.2.1 Inhalation Exposure 

Adverse health effects in humans associated with acute and occupational inhalation exposure to 

1,2-dichloroethane vapor were described in a number of studies. A case study reported by Nouchi et al. 

(1984) detailed the clinical effects, blood chemistry, and autopsy findings of a 51-year-old man who died 

after being exposed to 1,2-dichloroethane vapor for 30 minutes while removing 1,2-dichloroethane 

residue from the hold of an oil tanker. Exposure is likely to have occurred both by the inhalation and 

dermal routes. No estimate of the exposure concentration was available, although exposure conditions 

were described as a “thick vapor of dichloroethane.” This study, considered a reliable description of the 

manifestations of 1,2-dichloroethane-induced toxic effects in humans, is the source for much of the 

discussion of human data in this section. The available information suggests that massive, acute 

inhalation exposure to 1,2-dichloroethane can induce neurotoxic, nephrotoxic, and hepatotoxic effects in 

humans, as well as respiratory distress, cardiac arrhythmia, nausea, and vomiting. The possibility that 

existing medical conditions contributed to the observed symptoms and autopsy findings could not be 

evaluated because the individual’s medical and behavioral histories were not reported. No information 

was located regarding immunological, reproductive, or developmental effects in humans following 

inhalation exposure to 1,2-dichloroethane. 

Although considerable information is available on the effects of 1,2-dichloroethane following inhalation 

exposure in laboratory animals, many of the short-term studies used only a limited number of animals and 

are, therefore, of only limited utility. Targets of 1,2-dichloroethane inhalation toxicity in animals include 

the immune system, central nervous system, liver, and kidney. Limited evidence suggests that the heart 

may also be a target organ. 1,2-Dichloroethane has also produced genotoxic effects in animals exposed 

by inhalation (see Section 3.3). 

Table 3-1 and Figure 3-1 describe the health effects observed in experimental animals associated with 

exposure level and exposure duration. Effects of 1,2-dichloroethane in humans are not included in the 

LSE table and figure because exposure levels were not reported and the effects investigated were not 

subtle. 













1,2-DICHLOROETHANE 37 

3. HEALTH EFFECTS 

3.2.1.1 Death 

Exposure to concentrated 1,2-dichloroethane vapor can be lethal to humans. A 51-year-old man who 

inhaled concentrated vapor for only 30 minutes died 5 days later from cardiac arrhythmia (Nouchi et al. 

1984). No attempt was made to estimate the actual exposure concentration, although it was described as a 

“thick vapor of dichloroethane.” An autopsy revealed congestion of the lungs, degenerative changes in 

the myocardium, liver necrosis, renal tubular necrosis, and shrunken nerve cells in the brain. 

In animals, acute inhalation exposure to 1,2-dichloroethane in sufficient concentrations also causes death. 

Heppel et al. (1945, 1946) and Spencer et al. (1951) examined the toxic effects of inhaled 1,2-dichloroethane in a number of species. Acute intermittent exposure (#14 days) resulted in death in rabbits at 

100 ppm, in rats and guinea pigs at 400 ppm, and in mice, and dogs at 1,500 ppm. These were the lowest 

exposure concentrations that produced death in animals. Gross observations at necropsy revealed liver 

and kidney effects ranging from increased organ weight to necrosis, pulmonary congestion, and fatty 

infiltration and degeneration of the myocardium (Heppel et al. 1945, 1946; Spencer et al. 1951). An LC50 

of 1,000 ppm was determined for an 8-hour exposure in rats; shorter exposure durations resulted in higher 

LC50 values (Spencer et al. 1951). Necropsy of these rats revealed histopathological changes in the liver 

and kidney. High mortality (10/16 died) was seen in rat dams exposed to 300 ppm for 7 hours/day on 

9 consecutive days during gestation (Rao et al. 1980; Schlacter et al. 1979). 

Intermediate-duration intermittent exposures (6–25 weeks) caused deaths in guinea pigs, rats, and mice 

exposed to 200 ppm, rats and rabbits exposed to 400 ppm, and dogs, cats, and monkeys exposed to 

1,000 ppm (Heppel et al. 1946). Necropsy of these animals showed liver, kidney, heart, and lung effects 

similar to those observed following acute exposure. In a chronic inhalation study, there was no exposurerelated effect on survival in rats that were intermittently exposed to 50 ppm of 1,2-dichloroethane for 

2 years (Cheever et al. 1990). 

The LC50 value and LOAEL values from each reliable study for death in each species and duration 

category are presented in Table 3-1 and plotted in Figure 3-1. 
 

 

1,2-DICHLOROETHANE 38 

3. HEALTH EFFECTS 

3.2.1.2 Systemic Effects 

The systemic effects of 1,2-dichloroethane in humans and animals after inhalation exposure are discussed 

below. The highest NOAEL values and all LOAEL values from each reliable study for all systemic end 

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

Respiratory Effects. Short-term exposure to concentrated 1,2-dichloroethane in air may produce 

adverse respiratory effects in humans. In the case study reported by Nouchi et al. (1984), respiratory 

distress was reported 20 hours after the initial exposure; autopsy revealed that the lungs were severely 

congested and edematous. Chronic bronchitis and a dry pharynx were reported in a packing plant 

employee following 5 months of repeated exposures to unreported air concentrations of 

1,2-dichloroethane (McNally and Fostvedt 1941), but the authors regarded the symptoms as transitory. 

In animals, acute exposure to high concentrations of 1,2-dichloroethane was also associated with 

pulmonary congestion. A single 7-hour exposure to 3,000 ppm of 1,2-dichloroethane produced death 

with accompanying pulmonary congestion in mice, rats, rabbits, and guinea pigs (Heppel et al. 1945). 

Lower concentrations of 1,2-dichloroethane did not produce lung lesions. 

No pulmonary lesions were found by histological examination in rats and mice exposed to 100 ppm 

intermittently for 4–15 weeks, rabbits and monkeys exposed to 200 ppm intermittently for 25 weeks, or 

dogs exposed to 400 ppm intermittently for 8 months (Heppel et al. 1946). A limited number of rabbits, 

monkeys, and dogs were exposed, and not all of these animals were histologically examined. Similarly, 

there were no histopathological changes in the lung following intermittent exposures to 200 ppm for 

28–35 weeks in rats and guinea pigs, or 400 ppm for 33–35 weeks in rabbits (Spencer et al. 1951). 

Chronic intermittent exposure to 50 ppm of 1,2-dichloroethane for 2 years caused no histological 

alterations in respiratory tract of rats (Cheever et al. 1990). 

Cardiovascular Effects. Autopsy findings in a 51-year-old man included diffuse degenerative 

changes of the myocardium such as fragmentation, loss of nuclei of myocardial fibers, and interstitial 

edema (Nouchi et al. 1984); death was attributed to cardiac arrhythmia. However, since Nouchi et al. 

(1984) did not report on the medical and behavioral history of the individual, data were insufficient to 

conclude that these cardiac effects were due exclusively to 1,2-dichloroethane. Blood pressure was 

within the normal range in two packing plant employees subsequent to repeated occupational exposures 
 

 

1,2-DICHLOROETHANE 39 

3. HEALTH EFFECTS 

to unreported air concentrations of 1,2-dichloroethane over 2- or 5-month periods (McNally and Fostvedt 

1941). 

Cardiac lesions have also been reported in animals exposed to 1,2-dichloroethane. Acute lethal 

concentrations produced myocarditis in rats, dogs, and monkeys (Heppel et al. 1946). Guinea pigs that 

died following intermittent exposure to $200 ppm for 25 weeks had fatty infiltration and degeneration of 

the heart (Heppel et al. 1946). Among animals that survived intermediate-duration exposure to 

1,2-dichloroethane, cardiac changes were observed only in monkeys. Fat droplets were found in the 

myocardium of 2 monkeys intermittently exposed to 200 ppm for 25 weeks; no control animals were used 

(Heppel et al. 1946). No cardiovascular lesions were seen upon gross or microscopic examination in rats 

and mice intermittently exposed to 100 ppm for 4–15 weeks, in rabbits intermittently exposed to 200 ppm 

for 25 weeks, or in dogs intermittently exposed to 400 ppm for 8 months (Heppel et al. 1946). However, 

only two to six rabbits and three dogs per exposure level were tested, and histopathology was conducted 

on only a few animals. Similarly, there were no histopathological changes in the heart following 

intermittent exposures to 200 ppm for 28–35 weeks in rats and guinea pigs, or 400 ppm for 33–35 weeks 

in rabbits (Spencer et al. 1951). In a chronic study, intermittent exposure to 50 ppm of 1,2-dichloroethane 

for 2 years failed to produce cardiovascular lesions in rats (Cheever et al. 1990). 

Gastrointestinal Effects. A 51-year-old man who inhaled a thick vapor of 1,2-dichloroethane for 

30 minutes vomited periodically immediately following exposure (Nouchi et al. 1984). He died 5 days 

later. Nausea and vomiting were reported shortly following a single 4-hour occupational exposure in 

three knitting factory workers who wrung out yarn that had soaked in an open vat of 1,2-dichloroethane 

(Wirtschafter and Schwartz 1939). Two packing plant employees who were repeatedly exposed to 

unreported air concentrations of 1,2-dichloroethane on the job for 2 to 5 months experienced periods of 

epigastric pain, nausea, and vomiting (McNally and Fostvedt 1941). 

In animal studies, gastrointestinal effects, including emesis and passing of red watery stools, preceded 

death in dogs intermittently exposed to 1,500 ppm of 1,2-dichloroethane for 6 days (Heppel et al. 1945). 

Congestion of the gastrointestinal tract was noted in these animals at necropsy. Gastrointestinal lesions 

were not found in rats exposed to 50 ppm of 1,2-dichloroethane for 2 years (Cheever et al. 1990). 

Hematological Effects. Transient leukocytosis was reported during 5 days subsequent to a single 

4-hour occupational exposure in three knitting factory workers who wrung out yarn that had soaked in an 

open vat of 1,2-dichloroethane (Wirtschafter and Schwartz 1939). McNally and Fostvedt (1941) 
 

 

1,2-DICHLOROETHANE 40 

3. HEALTH EFFECTS 

indicated that hematological parameters (hemoglobin concentration, erythrocyte count, leukocyte count, 

and differential counts) in packing plant workers were not adversely affected subsequent to repeated 

occupational exposures to unreported (but potentially occasionally high) air concentrations of 

1,2-dichloroethane over 2- or 5-month periods. 

Only one study provided any indication of hematological effects in animals. Increased plasma 

prothrombin clotting time was reported in 2 monkeys exposed to 400 ppm of 1,2-dichloroethane 

intermittently for 8–12 days (Spencer et al. 1951). This study was limited because only two monkeys 

were examined and one moribund monkey was killed after eight exposures. Intermediate-duration studies 

of 1,2-dichloroethane found no hematological changes in rats, guinea pigs, rabbits, or dogs following 

intermittent exposures to 200–400 ppm for .32–35 weeks (Heppel et al. 1946; Spencer et al. 1951). 

Chronic exposure to 50 ppm for 2 years did not produce indications of blood cell changes in rats as 

detectable by histological examination of the spleen and bone marrow (Cheever et al. 1990); blood 

parameters were not monitored, limiting the usefulness of the study for assessing hematological effects. 

Musculoskeletal Effects. No studies were located regarding musculoskeletal effects in humans 

following inhalation exposure to 1,2-dichloroethane. 

Histological examination of skeletal muscle and skin showed no effects in rats that were intermittently 

exposed to 50 ppm of 1,2-dichloroethane for 2 years (Cheever et al. 1990). 

Hepatic Effects. The liver may be a target of 1,2-dichloroethane toxicity following inhalation 

exposure in humans. Nouchi et al. (1984) found an enlarged liver, high serum levels of lactate and 

ammonia, and increased serum levels of aspartate amino transferase (AST; also known as glutamic 

oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT; also known as glutamic pyruvic 

transaminase [SGPT]), 2 enzymes routinely used as indicators of liver damage, in a man exposed to 

concentrated 1,2-dichloroethane vapors for 30 minutes. The man died 5 days after exposure, and 

postmortem histopathological examination of the liver revealed extensive centrilobular necrosis and the 

presence of very few vacuolated cells, although it is not known to what degree this condition was preexisting. Mixed workplace exposure to 1,2-dichloroethane and vinyl chloride (exposure levels ranging up 

to 5.3 and 23.5 ppm, respectively, by area sampling, and up to 334 and 6.2 ppm, respectively, by personal 

sampling) was associated with a combined exposure-related increase in the prevalence of abnormal levels 

of ALT in a group of 251 male workers in a vinyl chloride manufacturing facility (Cheng et al. 1999); the 

contribution of 1,2-dichloroethane to the observed effect is uncertain. 
 

1,2-DICHLOROETHANE 41 

3. HEALTH EFFECTS 

There are also reports of hepatic effects in animals following acute-duration inhalation exposure to 

1,2-dichloroethane. Serum levels of enzymes used as indicators of hepatic damage (e.g., AST, ALT, 

sorbitol dehydrogenase [SDH]) were significantly elevated in rats exposed to $850 ppm for 4 hours 

(Brondeau et al. 1983). No effect was seen at 618 ppm. No histopathology was performed in this study 

to verify the occurrence of damage to the liver, but other studies have reported liver lesions in animals 

acutely exposed to lower concentrations. Monkeys intermittently exposed to 400 ppm for 8–12 days had 

marked fatty degeneration of the liver (Spencer et al. 1951). Monkeys exposed to 100 ppm did not show 

this effect. Slight parenchymatous degradation of the liver was found in guinea pigs exposed to 400 ppm 

for #14 days (Spencer et al. 1951). This study was limited by the use of a small number of animals. 

Longer-term exposure to 1,2-dichloroethane vapor produced hepatic effects in guinea pigs, dogs, and 

monkeys. Guinea pigs intermittently exposed to 100 ppm of 1,2-dichloroethane for 246 days exhibited 

increased liver weight and hepatic fatty infiltration (Spencer et al. 1951). Monkeys exposed to 200 ppm 

for 25 weeks and dogs exposed to 400 ppm for 8 months also exhibited fatty degeneration of the liver 

(Heppel et al. 1946). However, no hepatic effects were observed upon gross and microscopic 

examination in mice, rats, or rabbits intermittently exposed to concentrations of 100–400 ppm for 

4–30 weeks (Heppel et al. 1946; Spencer et al. 1951). There were a number of deficiencies in the studies 

of Heppel et al. (1946) and Spencer et al. (1951); many of the tests used a limited number of animals, and 

no control monkeys were examined by Heppel et al. (1946). 

In the only chronic inhalation study of 1,2-dichloroethane, groups of 50 male and 50 female rats were 

intermittently exposed to 50 ppm for 2 years (Cheever et al. 1990). No histological changes were found 

in the liver, bile duct, or any other tissues, indicating that the exposure concentration is a NOAEL. Based 

on the NOAEL of 50 ppm for liver effects, and considering the other evidence for hepatotoxicity of 

1,2-dichloroethane following longer-term vapor exposures, a chronic inhalation MRL of 0.6 ppm was 

calculated as described in the footnote to Table 3-1 and in Appendix A. 

Renal Effects. 1,2-Dichloroethane is acutely nephrotoxic in humans following inhalation exposure. 

In the case study reported by Nouchi et al. (1984), a man who inhaled 1,2-dichloroethane fumes for 

30 minutes had hepatic dysfunction and eventually exhibited kidney failure, as part of general organ 

failure, followed by cardiac arrest and death. Microscopic examination revealed acute tubular necrosis. 

Acute-duration inhalation exposure to 1,2-dichloroethane also produced renal effects in animals. Cloudy 

swelling of the renal tubular epithelium and increased kidney weight were reported in guinea pigs, and 
 

1,2-DICHLOROETHANE 42 

3. HEALTH EFFECTS 

degeneration of the tubular epithelium was reported in monkeys following intermittent exposure to 

400 ppm for 8–12 days (Spencer et al. 1951). No renal effects were noted in monkeys exposed to 

100 ppm for 8–12 days. These were the only species examined for renal effects following acute 

exposure, and only a small number of animals was examined in each case. 

Kidney lesions have also been reported following longer-term exposure of animals to 1,2-dichloroethane. 

Dogs intermittently exposed to 400 ppm for 8 months exhibited fatty changes in the kidney (Heppel et al. 

1946). In guinea pigs, degeneration of the kidney was observed, but only at lethal concentrations (Heppel 

et al. 1946). Renal effects were not detected in rats, mice, guinea pigs, or rabbits intermittently exposed 

to 100–400 ppm of 1,2-dichloroethane for 4–30 weeks (Heppel et al. 1946; Spencer et al. 1951). In all of 

these studies, a limited number of animals were exposed, and only a few of those were examined for 

histopathology. In a chronic study, no histopathological changes developed in the kidneys of rats 

exposed to 50 ppm of 1,2-dichloroethane intermittently for 2 years (Cheever et al. 1990). 

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

exposure to 1,2-dichloroethane. 

Endocrine function has not been evaluated in inhalation toxicity studies in animals. Histological 

examinations of endocrine system tissues were performed in several studies with essentially negative 

results, but lack of histopathology does not necessarily indicate that there were no functional 

endocrinologic changes. Acute intermittent exposure to 1,2-dichloroethane caused congestion of the 

adrenal cortex in guinea pigs exposed to 1,500 ppm for 4 days (Heppel et al. 1945, 1946), but this 

exposure was lethal in most animals. An intermediate-duration study noted calcification of the adrenal 

medulla in 1 of 2 monkeys intermittently exposed to 200 ppm for 25 weeks (Heppel et al. 1946), but the 

evidence for this effect is inconclusive because only 2 monkeys were studied, no control animals were 

examined, and adrenal effects have not been reported in other long-term inhalation studies by Heppel et 

al. (1946) or other investigators. Histopathological examinations failed to detect changes in endocrine 

tissues following intermittent exposures to 100 ppm for 4 or 15 weeks in rats and mice (Heppel et al. 

1946), 200 ppm for .25–35 weeks in rats, guinea pigs, and rabbits (Heppel et al. 1946; Spencer et al. 

1951), 200 or 400 ppm for .32–35 weeks in rabbits (Heppel et al. 1946; Spencer et al. 1951), or 400 ppm 

for 8 months in dogs (Heppel et al. 1946). The histological examinations in these studies were limited to 

the adrenal gland and/or pancreas. 
 

 

 

1,2-DICHLOROETHANE 43 

3. HEALTH EFFECTS 

The only chronic inhalation study of 1,2-dichloroethane found that intermittent exposure to 50 ppm for 

2 years induced a slight increase in the incidence of unspecified basophilic focal changes in the pancreas 

in female rats, but no histological alterations in the adrenal, thyroid, parathyroid, or pituitary glands 

(Cheever et al. 1990). The toxicological significance of the pancreatic changes is unclear because the 

incidence was not reported, the effect was induced in only one sex (females), additional exposure levels 

were not tested, and the study was designed to evaluate carcinogenicity. 

The highest NOAEL values and all LOAEL values from each reliable study for endocrine effects in each 

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

Dermal Effects. No studies were located regarding dermal effects in humans after inhalation 

exposure to 1,2-dichloroethane. 

Histological examinations showed no changes in the skin of rats exposed to 50 ppm of 1,2-dichloroethane 

intermittently for 2 years (Cheever et al. 1990). 

Ocular Effects. No studies were located regarding ocular effects in humans after inhalation exposure 

to 1,2-dichloroethane. 

Ocular effects reported in animals acutely exposed to 1,2-dichloroethane by inhalation were corneal 

clouding and lacrimation (Heppel et al. 1945, 1946). These effects probably resulted from direct ocular 

contact with 1,2-dichloroethane vapor and are discussed in more detail in Section 3.2.3. In a chronic 

study, rats that were exposed to 50 ppm of 1,2-dichloroethane intermittently for 2 years had no 

histological changes in the eyes (Cheever et al. 1990). 

Body Weight Effects. No studies were located regarding effects on body weight in humans after 

acute inhalation exposure to 1,2-dichloroethane. A weight loss of 10 pounds was reported in a packing 

plant employee who was repeatedly exposed to unreported, but potentially high, air concentrations of 

1,2-dichloroethane for 9 weeks, although the period over which the weight was lost relative to the 

exposure period was not reported (McNally and Fostvedt 1941). 

Adverse changes in body weight (decreased gain or weight loss) occurred in maternal rats that were 

intermittently exposed to 300 or 329 ppm of 1,2-dichloroethane during gestation, although these effects 

were not observed at 100 or 254 ppm (Payan et al. 1995; Rao et al. 1987; Schlacter et al. 1979). No 
1,2-DICHLOROETHANE 44 

3. HEALTH EFFECTS 

changes in body weight gain were caused by intermittent exposures to 200 ppm for 28–35 weeks in rats 

and guinea pigs (Spencer et al. 1951), 400 ppm for 33–35 weeks in rabbits (Spencer et al. 1951), or 

50 ppm for 2 years in rats (Cheever et al. 1990). 

3.2.1.3 Immunological and Lymphoreticular Effects 

No studies were located regarding immunological effects in humans after inhalation exposure to 

1,2-dichloroethane. 

Acute intermittent exposure to 1,2-dichloroethane caused chronic splenitis in rats exposed to 1,000 ppm 

for 14 days (Heppel et al. 1946), but this exposure was lethal in most of the animals tested. 

There is evidence that acute exposure to 1,2-dichloroethane affects the ability to fight infection arising 

from inhaled microbial pathogens in animals. Female mice (4–5 weeks old) exposed to 5.4–10.8 ppm of 

1,2-dichloroethane for 3 hours exhibited increased susceptibility to Streptococcus zooepidemicus (i.e., 

increased mortality following infection), suggesting reduced pulmonary defenses in the exposed mice 

(Sherwood et al. 1987); male mice were not evaluated. No effect was observed at 2.3 ppm. Additionally, 

female mice that were similarly exposed to 10.8 ppm had reduced bactericidal activity in the lungs 

3 hours after exposure to Klebsiella pneumoniae. Male rats exposed to #100 ppm for 5 hours/day for 

12 days, or to a single 5-hour exposure to #200 ppm, did not exhibit reduced bactericidal activity after 

K. pneumoniae challenge (female rats were not evaluated); mortality following S. zooepidemicus 

challenge was not evaluated in rats. In addition, no effects on lymphocyte function (as indicated by 

blastogenesis to T- and B-cell mitogens) were seen in rats exposed to #100 ppm 5 hours/day for 12 days. 

Results reported in Sherwood et al. (1987) suggest that rats may be less susceptible to the detrimental 

immunological effects of 1,2-dichloroethane than mice and/or that male rodents are less susceptible than 

females. The relevance of the immunological effects in mice to human immunotoxicity is uncertain, since 

the massive bacterial challenges given to mice in the study are unlikely to be representative of normal 

immunological challenges in humans. In addition, Sherwood et al. (1987) concluded that the interspecies 

differences in immunotoxicity observed in the study suggest against extrapolating from animals to 

humans. 

Immune function has not been evaluated in intermediate- or chronic-duration inhalation studies of 

1,2-dichloroethane, although histopathological examinations failed to detect lesions in immune system 

tissues following intermittent exposure to 200 ppm for 212–246 days in rats and guinea pigs (Spencer et 
1,2-DICHLOROETHANE 45 

3. HEALTH EFFECTS 

al. 1951), to 400 ppm for 232–248 days in rabbits (Spencer et al. 1951), or to 50 ppm for 2 years in rats 

(Cheever et al. 1990). 

The highest NOAEL values and all LOAEL values from each reliable study for immunological effects in 

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

3.2.1.4 Neurological Effects 

Inhalation of high concentrations of 1,2-dichloroethane can affect the nervous system of humans. It has 

been reported that 1,2-dichloroethane is an anesthetic narcotic in humans, and that it is as potent an 

anesthetic as gasoline, benzene, carbon tetrachloride, and chloroform when inhaled for periods of an hour 

or more (Garrison and Leadingham 1954). A 51-year-old sailor exposed to a concentrated vapor of 

1,2-dichloroethane for 30 minutes suffered central nervous system effects, such as irritability and periodic 

vomiting, immediately following exposure (Nouchi et al. 1984). Twenty hours later, he was drowsy and 

became delirious and tremulous; he lapsed into a coma 4 hours later, with a generalized continuous clonic 

jerk. His electroencephalogram showed slow wave abnormality. He died 5 days after exposure. Upon 

autopsy, the Purkinje cell layer of his cerebellum showed a shrunken appearance with pyknotic nuclei. 

Weakness, dizziness, and trembling were reported shortly following a single 4-hour occupational 

exposure in three knitting factory workers who wrung out yarn that had soaked in an open vat of 

1,2-dichloroethane (Wirtschafter and Schwartz 1939). Two packing plant employees who were 

repeatedly exposed to unreported air concentrations of 1,2-dichloroethane on the job for 2–5 months 

reported drowsiness during work hours or sleeplessness, and upon physical examination, they exhibited 

nervousness, “marked” nystagmus, tremor of the tongue, or sluggish patellar reflex (McNally and 

Fostvedt 1941). 

Acute-duration exposure to concentrated 1,2-dichloroethane also produces neurological effects in 

animals. Rats experienced central nervous system depression after exposure to $12,000 ppm for 

30 minutes (Spencer et al. 1951); the authors did not conclusively attribute apparent neurological effects 

of inactivity, stupor, and “slowness of response to handling” observed at #3,000 ppm to central nervous 

system depression. Exposure to 20,000 ppm for 15 minutes resulted in central nervous system depression 

sufficient to cause death; no histopathology was conducted on the brain or peripheral nerves. Uncertain 

gait, narcosis, prostration, or unconsciousness were seen in rats, guinea pigs, and rabbits exposed once to 

3,000 ppm for 7 hours, but were not reported at 1,500 ppm; 7-hour exposures to 1,500 ppm on 

5 consecutive days induced transitory tremors, convulsions, or coma in rats and dogs (Heppel et al. 1945). 
1,2-DICHLOROETHANE 46 

3. HEALTH EFFECTS 

Longer-term exposure to lower concentrations of 1,2-dichloroethane did not appear to produce 

neurological effects, although sensitive indicators of subtle neurological effects were not examined. 

Negative results were obtained by physical examination (without histopathology) of dogs intermittently 

exposed to 400 ppm for 8 months (Heppel et al. 1946) and by histopathological examination of the brain 

from rats intermittently exposed to 50 ppm for 2 years (Cheever et al. 1990). The highest NOAEL values 

for neurological effects in each species and duration category are recorded in Table 3-1 and plotted in 

Figure 3-1. 

3.2.1.5 Reproductive Effects 

Studies regarding reproductive effects in humans after inhalation exposure to 1,2-dichloroethane are 

limited to a single account of increased rates of premature births in female workers and in wives of male 

workers who were exposed in a Chinese synthetic fiber factory (Zhao et al. 1989). Concentrations of 

1,2-dichloroethane ranged from 0.4 to 384 ppm at two locations. Female subjects were exposed 

throughout pregnancy, and male workers were exposed for at least 1 year before their wives became 

pregnant. These results should be treated with caution because the study evaluated a small number of 

subjects (44 male and 54 female exposed workers), the authors indicated that co-exposure to other 

chemicals occurred in most cases, and the study was generally deficient in reporting the study design 

including accounting for possible confounding environmental and behavioral factors. 

Some studies in rodents (Vozovaya 1974, 1977; Zhao et al. 1989) found that inhalation exposure to 

1,2-dichloroethane either prior to mating and continuing into gestation or throughout gestation caused 

pre-implantation loss and embryolethality, although the reliability of these studies is unclear because of 

deficiencies in reporting study design and results. Pre-implantation loss was reportedly increased (31.0% 

compared to 10.2% in controls, p<0.05) in unspecified rodents that were exposed to 51.9 ppm “during the 

entire pregnancy period”; one account of the study indicated that a 2-week pre-mating exposure also 

occurred (Zhao et al. 1997), although this could not be corroborated from the original study (Zhao et al. 

1989). Intermittent exposure of rats to 4.7±7 ppm for 4 months prior to the mating period, followed by 

inhalation exposure during pregnancy, produced a statistically significant (p<0.01) increase in embryo 

mortality (Vozovaya 1977). Fertility was decreased, and stillbirths and perinatal mortality were increased 

in the first generation of a two-generation reproduction study in rats that were intermittently exposed to 

14 ppm of 1,2-dichloroethane over a period of 6 months (Vozovaya 1974). In contrast to the studies 

summarized above, a well-designed study by Rao et al. (1980) showed no adverse effects on the fertility, 

gestation, or survival in pups of male and female rats intermittently exposed to #150 ppm for 60 days pre­
1,2-DICHLOROETHANE 47 

3. HEALTH EFFECTS 

mating, then throughout mating, gestation, and lactation (excluding gestation day 21 through postpartum 

day 4). No gross or histopathological lesions were observed in reproductive organs of rats exposed to 

50 ppm intermittently for 2 years (Cheever et al. 1990). 

The highest NOAEL values and all LOAEL values from each reliable study for reproductive effects in 

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

3.2.1.6 Developmental Effects 

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

1,2-dichloroethane. 

The overall evidence from inhalation studies in rats and rabbits indicates that 1,2-dichloroethane is not a 

developmental toxicant. 1,2-Dichloroethane was not fetotoxic or teratogenic in the offspring of rats that 

were intermittently exposed to 100 ppm on days 6–15 of gestation (Rao et al. 1980; Schlacter et al. 1979). 

Exposure to 300 ppm produced high maternal mortality with fetolethality, and one rat had a total 

resorption of the litter. Another study similarly found that exposure to 1,2-dichloroethane during 

gestation days 6–20 was not fetotoxic or teratogenic to rats at concentrations as high as those producing 

maternal toxicity (329 ppm) (Payan et al. 1995). There were no exposure-related changes in numbers of 

implantations, resorptions, and live fetuses, fetal sex ratio or body weights, or external, visceral, or 

skeletal development, although maternal body weight gain was 24% reduced at 329 ppm; no maternal 

effects occurred at lower concentrations (150–254 ppm). Developmental toxicity was reported in one 

study in rats, but the reliability of the data is unclear (Vozovaya 1977). Exposure to 4.7±7 ppm of 

1,2-dichloroethane for 4 months before mating followed by exposure during pregnancy was embryotoxic 

and caused hematomas in the head and neck region and anterior extremities of the fetuses. The reliability 

of the Vozovaya (1977) data cannot be assessed due to lack of statistical analysis and uncertainties in the 

reported results. Zhao (1984) reported no developmental changes in F1 and F2 generations of mice after 

the parental dams were exposed by inhalation for 4 hours per day to up to 62.5 ppm on gestation days 

6–15, or to 250 ppm on gestation days 9 and 10. The F1 generation was not postnatally exposed to 

1,2-dichloroethane. No changes were observed in the following parameters: fetal survival, length, or 

weight; external, skeletal, or visceral appearance; pup survival; onset of pup physical changes and reflex 

acquisition; or pup weight gain. In spite of reporting deficiencies leading to critical uncertainties in the 

adequacy of the study design, the results are suggestive that 1,2-dichloroethane is not developmentally 

toxic in mice under reported study conditions. 
1,2-DICHLOROETHANE 48 

3. HEALTH EFFECTS 

Rabbits that were intermittently exposed to 100 or 300 ppm of 1,2-dichloroethane on days 6–18 of 

gestation experienced some maternal deaths, but there were no chemical-related fetotoxic or teratogenic 

effects as indicated by pregnancy and resorption incidences, litter size, fetal body measurements, and softtissue and skeletal examinations (Rao et al. 1980). 

The highest NOAEL values from each reliable study for developmental effects in each species and 

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

3.2.1.7 Cancer 

Specific evidence associating inhalation exposure to 1,2-dichloroethane with the occurrence of cancer in 

humans was not found in the literature reviewed. Several epidemiological studies have been conducted 

on workers in the chemical industry to investigate the high incidence of brain tumors observed among 

workers employed in petrochemical plants (Austin and Schnatter 1983a, 1983b; Reeve et al. 1983; Teta et 

al. 1989; Waxweiler et al. 1983), the incidence of stomach cancer and leukemia at a plant that used 

1,2-dichloroethane in the production of ethylene oxide (Hogstedt et al. 1979), and the increased deaths 

due to pancreatic cancer and lymphatic and hematopoietic cancers in a cohort of workers in chlorohydrin 

production plants where 1,2-dichloroethane was a production byproduct (Benson and Teta 1993). 

Increased risk of primary breast cancer (odds ratio [OR]=2.2; 95% confidence interval [CI]=1.4–3.6; no 

latency) was observed in Danish men who were occupationally exposed to unreported levels of gasoline 

and combustion products containing 1,2-dichloroethane, compared to workers who were not exposed 

(according to job type and trade code) (Hansen 2000). The OR increased to 2.5 (95% CI=1.3–4.5) among 

workers with a latency of >10 years (Hansen 2000). Male residents in areas near a municipal solid waste 

site in Montreal, Quebec, which emitted airborne 1,2-dichloroethane (among a number of other volatile 

substances) showed increased risk of stomach cancers (relative risk [RR]=1.3; 95% CI=1.0–1.5), liver and 

intrahepatic bile duct cancers (RR=1.3; 95% CI=0.9–1.8), and cancers of the trachea, bronchus, and lung 

(RR=1.1; 95% CI=1.0–1.2) (Goldberg et al. 1995). Female residents showed increased risk of stomach 

cancer (RR=1.2; 95% CI=0.9–1.5) and cervix uteri cancer (RR=1.2; 95% CI=1.0–1.5). None of these 

epidemiology studies dealt with 1,2-dichloroethane exposure exclusively, and the concurrent exposure to 

other chemicals or solvents confounded the results. None of these studies could specifically link chemical 

exposure with the excess cancer incidence. 

The carcinogenicity of inhaled 1,2-dichloroethane has been evaluated in chronic experiments in both rats 

and mice. Maltoni et al. (1980) exposed Sprague-Dawley rats and Swiss mice to 1,2-dichloroethane at 
1,2-DICHLOROETHANE 49 

3. HEALTH EFFECTS 

concentrations of #250 ppm 7 hours/day, 5 days/week, for 78 weeks; no treatment-related increase in the 

incidence of tumors was observed in treated rats or mice. However, this study is limited for a number of 

reasons. Chemical administration and study duration were less than lifetime. Furthermore, the maximum 

tolerated dose was exceeded at the highest dose tested (250 ppm), and survival in mice was poor. 

Therefore, only a small number of surviving animals were at risk for late-developing tumors. The 

plausible explanations for the negative results obtained in this study may include the differences in the 

metabolic pathways and the amount of toxic metabolites reaching the target tissues (see Section 3.5.1). A 

chronic study in which rats were exposed to 50 ppm of 1,2-dichloroethane intermittently for 2 years also 

failed to find carcinogenic effects (Cheever et al. 1990). However, this study was limited by the use of a 

single dose level that may have been considerably lower than the maximum tolerated dose (MTD) (the 

relatively low exposure concentration of 50 ppm was chosen because it was the U.S. occupational 

standard at the time the experiment was initiated). An abstract reported that inhalation exposure to 

1,2-dichloroethane at unreported levels for 6 hours/day, 5 days/week, for 2 years induced mammary gland 

fibroadenomas and subcutis fibromas in both sexes of F344 rats, mammary gland adenocarcinomas/ 

adenomas in female rats, peritoneal mesotheliomas in male rats, hepatic hemangiosarcomas in male BDF1 

mice, and bronchio-alveolar carcinomas/adenomas, mammary gland adenocarcinomas, and uterine 

endometrial stromal polyps in female mice (Matsushima et al. 1998). The full study report was not 

located and, thus, adequacy of the study design and conduct could not be evaluated. 

3.2.2 Oral Exposure 

Information concerning the toxic effects of ingested 1,2-dichloroethane in humans was derived primarily 

from case reports of individuals who accidentally or intentionally ingested 1,2-dichloroethane. Only 

crude estimates of ingested dose were available, limiting the value of the data. The available information 

indicates that 1,2-dichloroethane can cause death from cardiac arrhythmia after a sufficient single oral 

dose (Garrison and Leadingham 1954; Hueper and Smith 1935; Martin et al. 1969; Schönborn et al. 

1970). Other symptoms reported include bronchitis, hemorrhagic gastritis and colitis, hepatocellular 

damage, renal tubular necrosis and calcification, central nervous system depression, and histological 

changes in brain tissue (Hueper and Smith 1935; Lochhead and Close 1951; Przezdziak and Bakula 1975; 

Yodaiken and Babcock 1973). No studies were located regarding immunological, reproductive, or 

developmental effects in humans following oral exposure to 1,2-dichloroethane. 

The toxicity of ingested 1,2-dichloroethane has been well studied in animals. Targets of 1,2-dichloroethane toxicity in orally exposed animals included the immune system, central nervous system, liver, and 
1,2-DICHLOROETHANE 50 

3. HEALTH EFFECTS 

kidney. 1,2-Dichloroethane also produced genotoxic effects (see Section 3.3) and carcinogenic effects in 

animals exposed by this route. 

Table 3-2 and Figure 3-2 describe the health effects observed in laboratory animals associated with oral 

exposure levels at varying time and exposure durations. 

3.2.2.1 Death 

Ingestion of large amounts of 1,2-dichloroethane may be lethal to humans. Hueper and Smith (1935) 

reported a case in which a 63-year-old man accidentally swallowed approximately 2 ounces (60 mL) of 

1,2-dichloroethane and died 22 hours later of circulatory failure. A 50-year-old man mistakenly ingested 

approximately 30 mL of 1,2-dichloroethane and died after 10 hours (Lochhead and Close 1951). A 

14-year-old boy died 5 days after ingesting 15 mL of 1,2-dichloroethane (Yodaiken and Babcock 1973). 

A 30-year-old man ingested approximately 40 mL of 1,2-dichloroethane and died 28 hours later (Garrison 

and Leadingham 1954). Another man who drank 50 mL of 1,2-dichloroethane died 22 hours later of 

circulatory failure (Hueper and Smith 1935). Schönborn et al. (1970) reported a case of an 18-year-old 

man who became drowsy and cyanotic, and exhibited bradycardia after drinking approximately 50 mL of 

Marament (a pharmaceutical formulation), which was equivalent to 50 g of 1,2-dichloroethane 

(714 mg/kg, assuming 70 kg body weight); he died 17 hours later in a state of circulatory shock. A 

hospital patient accidentally ingested a “small” quantity of 1,2-dichloroethane and died 18 hours later 

after intensive supportive measures were taken; the immediate cause of death was not reported (Hubbs 

and Prusmack 1955). In two other cases of 1,2-dichloroethane poisoning, the patients drank 15–20 mL 

Marament; they suffered gastrointestinal disorders and were discharged from the hospital in a few days 

(Schönborn et al. 1970). These patients received prophylactic heparinization 3–4 days before the 

appearance of blood coagulation disorders. Only crude estimates of ingested dose were available, 

limiting the value of the data. 

Death has also occurred in animals following oral exposure to 1,2-dichloroethane. An acute oral LD50 

value of 680 mg/kg has been reported for rats (McCollister et al. 1956); treatment was by gavage, but the 

dosage levels tested and the time of death after administration were not reported. Daily gavage doses of 

300 mg/kg for 10–14 days caused 80–100% mortality in rats (Daniel et al. 1994; van Esch et al. 1977). 

Munson et al. (1982) used log probability analysis to determine LD50 values of 489 and 413 mg/kg for 

male and female mice, respectively; the mice died over a 48-hour period following gavage. 





















 

1,2-DICHLOROETHANE 72 

3. HEALTH EFFECTS 

Intermediate-duration studies in animals indicate that the lethality of 1,2-dichloroethane is much higher 

by gavage than by ingestion in drinking water. Complete mortality occurred at 398 mg/kg/day in male 

mice and at 631 mg/kg/day in female mice exposed to 1,2-dichloroethane by gavage for 6 weeks (NCI 

1978). Similarly, in rats exposed by gavage for 6 or 13 weeks, doses $240 mg/kg/day caused deaths in 

all animals (NTP 1991a). However, much higher dose levels were required to produce death following 

drinking water exposure. No deaths occurred among rats exposed to doses #727 mg/kg/day in the 

drinking water for 13 weeks (NTP 1991a). Mice that were exposed to 1,2-dichloroethane in drinking 

water for 13 weeks experienced mortality only at the high dose of 4,930 mg/kg/day (NTP 1991a). The 

mortality in the NTP (1991a) drinking water studies began to increase during the first 2 weeks of 

exposure and approached or reached 100% after 13 weeks (NTP 1991a). In the 13-week gavage study, 

240 and 480 mg/kg/day produced 100% mortality in male rats within 13 weeks and 3 days, respectively 

(NTP 1991a). 

Chronic exposure to 1,2-dichloroethane by gavage caused reduced survival in rats and mice. Treatment 

with 95 mg/kg/day for 78 weeks caused 84% mortality in rats (NCI 1978). The mortality was seen as 

early as week 2 and became substantial after 15 weeks. The data suggest that the dose levels tested might 

be lethal to rats under both acute and chronic conditions. In mice, 72% mortality occurred in females 

exposed to 299 mg/kg/day by gavage for 78 weeks; mortality became evident after .10 weeks (NCI 

1978). 

The LD50 values and all LOAEL values from each reliable study for death in each species and duration 

category are presented in Table 3-2 and plotted in Figure 3-2. 

3.2.2.2 Systemic Effects 

The systemic effects of 1,2-dichloroethane in humans and animals after oral exposure are discussed 

below. The highest NOAEL values and all LOAEL values from each reliable study for systemic end 

points in each species and duration category are recorded in Table 3-2 and plotted in Figure 3-2. 

Respiratory Effects. The respiratory effects exhibited by individuals who died following acute oral 

exposure to 1,2-dichloroethane include congestion, pulmonary edema (at 570 mg/kg/day), dyspnea, and 

bronchitis (Hubbs and Prusmack 1955; Hueper and Smith 1935; Lochhead and Close 1951; Martin et 

al. 1969; Yodaiken and Babcock 1973). The pulmonary edema reported in the case report by Yodaiken 

and Babcock (1973) may have been chemical pneumonitis due to aspiration of 1,2-dichloroethane. 
 

 

1,2-DICHLOROETHANE 73 

3. HEALTH EFFECTS 

The literature reviewed provided no evidence that 1,2-dichloroethane induces adverse effects on the 

respiratory system following acute, intermediate, or chronic oral exposure in animals. Gross and 

histological examinations showed no effects in the respiratory tract following gavage exposure in rats 

treated with #100 mg/kg/day for 10 or 14 days (Daniel et al. 1994; van Esch et al. 1977), rats treated with 

#480 mg/kg/day for #90 days (Daniel et al. 1994; NTP 1991a; van Esch et al. 1977), or rats and mice 

treated with #95 and #299 mg/kg/day, respectively, for #78 weeks (NCI 1978). Similarly, no 

histopathological changes in the respiratory tract were found in rats and mice that ingested 

1,2-dichloroethane in the drinking water at doses of #492 and #4,210 mg/kg/day, respectively, for 

#90 days (NTP 1991a). The histological examinations performed by NTP (1991a) were more complete 

than in the other studies because they included the nasal cavity and turbinates in addition to the lungs and 

bronchi. Other studies in mice found no changes in lung weight or gross appearance following exposure 

to #49 mg/kg/day by gavage for 14 days or #189 mg/kg/day in drinking water for #90 days (Munson et 

al. 1982), but these results are limited by lack of histological examinations. 

Cardiovascular Effects. Clinical investigation of patients who died following acute ingestion of 

1,2-dichloroethane determined that cardiovascular insufficiency and hemorrhage were major factors 

contributing to death (Garrison and Leadingham 1954; Hueper and Smith 1935; Martin et al. 1969; 

Schönborn et al. 1970). Numerous surficial petechial hemorrhages of the heart were observed at autopsy 

in a man who died from ingesting a “small” quantity of 1,2-dichloroethane (Hubbs and Prusmack 1955). 

Cardiovascular histopathological effects were not found in animals orally exposed to 1,2-dichloroethane, 

even at lethal doses. Histological examinations showed no cardiovascular effects following gavage 

exposure in rats treated with #100 mg/kg/day for 10 days (Daniel et al. 1994), rats treated with 

#480 mg/kg/day for #90 days (Daniel et al. 1994; NTP 1991a; van Esch et al. 1977), or rats and mice 

treated with #95 and #299 mg/kg/day, respectively, for #78 weeks (NCI 1978). Similarly, no 

histopathological changes in the heart were found in rats and mice that ingested 1,2-dichloroethane in the 

drinking water at doses of #492 and #4,210 mg/kg/day, respectively, for #90 days (NTP 1991a). 

Gastrointestinal Effects. Gastrointestinal symptoms have been observed in humans prior to death 

following oral exposure to 570 or 714 mg/kg/day of 1,2-dichloroethane. These symptoms included 

nausea, vomiting, and diarrhea (Hueper and Smith 1935; Lochhead and Close 1951; Martin et al. 1969; 

Schönborn et al. 1970; Yodaiken and Babcock 1973). Hemorrhagic colitis, hemorrhagic gastritis, and 

focal hemorrhages of the gastrointestinal tract have also been reported upon autopsy (Garrison and 
 

1,2-DICHLOROETHANE 74 

3. HEALTH EFFECTS 

Leadingham 1954; Hubbs and Prusmack 1955; Hueper and Smith 1935; Lochhead and Close 1951; 

Martin et al. 1969; Schönborn et al. 1970). 

Gastrointestinal lesions have also been found in animals given bolus doses of 1,2-dichloroethane. 

Forestomach lesions developed in rats given gavage doses of 100 mg/kg/day for 10 days (minimal 

mucosal and submucosal inflammation), $240 mg/kg/day for #13 weeks (mild hyperplasia and 

inflammation), or $47 mg/kg/day for #78 weeks (acanthosis and hyperkeratosis) (Daniel et al. 1994; NCI 

1978; NTP 1991a). Similar lesions were not found in rats exposed to corresponding doses 

(#492 mg/kg/day) in the drinking water for 13 weeks or mice exposed to much higher doses 

(#4,210 mg/kg/day) in the drinking water for 13 weeks (NTP 1991a). No increase in histopathologies in 

the stomach or intestines was observed in rats after intermittent gavage doses of up to 90 mg/kg/day over 

a 90-day period (van Esch et al. 1977). The incidences of non-neoplastic lesions of the stomach, large 

intestine, and colon were also not increased in mice intermittently administered up to 299 mg/kg/day by 

gavage for 78 weeks (NCI 1978). The gastrointestinal lesions observed in humans and animals ingesting 

bolus doses are probably produced by direct contact with concentrated 1,2-dichloroethane; the 

concentration in drinking water (8,000 mg/L) tested by NTP (1991a), although close to the solubility limit 

for this chemical (9,000 mg/L), was apparently too low to have this effect. 

Hematological Effects. Adverse hematological effects, such as increased prothrombin time and 

reduction in blood clotting factors, were observed in 18- and 57-year-old men who had ingested 

approximately 40 mL ($570 mg/kg) of 1,2-dichloroethane (Martin et al. 1969; Schönborn et al. 1970) and 

in a 14-year-old boy who had ingested approximately 15 mL (360 mg/kg, using an approximate body 

weight of 51.3 kg [EPA 1988d]) of 1,2-dichloroethane (Yodaiken and Babcock 1973). These are only 

crude estimates of the ingested doses. The alterations in coagulation parameters described above may 

have been associated to some degree with liver dysfunction. The liver plays an important role in blood 

clotting homeostasis, and hepatic disorders may result in abnormalities in coagulation tests. The liver is 

the site of production of most of the plasma coagulant factors such as fibrinogen, prothrombin, and 

factors V, VII, IX, and X. 

Similar effects have not been reported in animals following oral exposure. However, a 30% decrease in 

leukocytes was reported in mice given daily gavage doses of 49 mg/kg of 1,2-dichloroethane for 2 weeks 

(Munson et al. 1982). This effect may have had some relation to immunosuppressive effects reported in 

the same study. Mice that ingested #189 mg/kg/day in the drinking water for 90 days did not exhibit any 

differences from control animals with regard to hemoglobin, hematocrit, red or white blood cell counts, or 
 

 

1,2-DICHLOROETHANE 75 

3. HEALTH EFFECTS 

platelets (Munson et al. 1982). Similarly, there were no hematological changes in mice exposed to 

#4,210 mg/kg/day in the drinking water for up to 13 weeks (NTP 1991a). In order to explain the 

apparent contradiction in their results, Munson et al. (1982) suggested that more 1,2-dichloroethane may 

enter systemic circulation when the animals are given a concentrated solution in bolus form, than when 

they are allowed to drink water containing lower concentrations of 1,2-dichloroethane. They also 

suggested that, during the longer exposure time, 1,2-dichloroethane might induce its own metabolism and 

therefore be removed from the blood and other organs more rapidly. In rats, hematological parameters 

were unaffected by exposure to #100 mg/kg/day by gavage for 10 or 14 days (Daniel et al. 1994; van 

Esch et al. 1977), #480 mg/kg/day by gavage for #90 days (Daniel et al. 1994; NTP 1991a; van Esch et 

al. 1977), or #492 mg/kg/day in drinking water for 90 days (NTP 1991a). 

Musculoskeletal Effects. No studies were located regarding musculoskeletal effects in humans after 

oral exposure to 1,2-dichloroethane. 

There is no indication that ingested 1,2-dichloroethane produces musculoskeletal effects in animals. 

Histological changes in muscle and bone were not observed in rats administered #100 mg/kg/day by 

gavage for 10 days (Daniel et al. 1994), in rats administered #480 mg/kg/day by gavage for #90 days 

(Daniel et al. 1994; NTP 1991a; van Esch et al. 1977), or in rats and mice exposed at #492 and 

#4,210 mg/kg/day, respectively, in drinking water for #90 days (NTP 1991a). 

Hepatic Effects. 1,2-Dichloroethane has been implicated as a hepatotoxin in humans after acute oral 

poisoning (Przezdziak and Bakula 1975). Ingestion of $570 mg/kg/day of 1,2-dichloroethane resulted in 

severe hepatocellular damage and liver atrophy (Martin et al. 1969) and necrosis (Schönborn et al. 1970), 

although the degree to which these conditions were pre-existing is unknown. No gross changes were 

reported in the liver of a man who died from ingesting a “small” quantity of 1,2-dichloroethane, but 

hepatocellular fatty vacuolation and inflammation, “engorged” hepatic vasculature, and mild lymphocytic 

infiltration of portal spaces were observed microscopically (Hubbs and Prusmack 1955). 

Studies in orally exposed animals have not found serious liver effects like those reported in humans. 

Hepatic biochemical changes consisting of a 15% increase in fat accumulation and increases in total 

triglycerides (indicative of liver damage), were observed in rats fed 80 mg/kg/day of 1,2-dichloroethane 

in the diet for 5–7 weeks (Alumot et al. 1976). Histological examinations were not performed, although 

liver weight was unchanged. The NOAEL for liver changes in this study was 30 mg/kg/day. Increased 

liver weight with no hepatic histological alterations occurred in intermediate-duration studies conducted 
 

1,2-DICHLOROETHANE 76 

3. HEALTH EFFECTS 

by NTP (1991a) in rats and mice. Following a 13-week gavage exposure in rats, both liver weight and 

liver-to-body-weight ratio were elevated in a dose-related fashion. The increase over controls was 

significant at 18–150 mg/kg/day in females and 120 mg/kg/day in males (liver weight was not measured 

in higher-dose animals because of mortality). Following a 13-week drinking water exposure, liver weight 

increases were noted at 60 mg/kg/day in rats (liver-to-body-weight ratio was significantly elevated at 

60–518 mg/kg/day in Sprague-Dawley males without corresponding decreases in body weight), and at 

249 mg/kg/day in mice (liver-to-body-weight ratio was significantly elevated in a dose-related manner at 

249–4,210 mg/kg/day in males without corresponding decreases in body weight). Similarly, relative liver 

weights were increased with no accompanying histopathological changes in rats administered 

#150 mg/kg/day by gavage for #90 days (Daniel et al. 1994; van Esch et al. 1977). In the absence of 

histopathological or biochemical changes in the liver, the changes in liver weight are not considered to be 

adverse effects. Based on these findings, the liver does not appear to be a sensitive target organ for 

1,2-dichloroethane toxicity in animals. 

Other animal studies of 1,2-dichloroethane did not find hepatic effects. No changes in liver weight were 

observed in mice exposed to #49 mg/kg/day by gavage for 14 days or #189 mg/kg/day in drinking water 

for 90 days (Munson et al. 1982); histology was not evaluated. Rats administered single gavage doses 

(80 mg/kg) of 1,2-dichloroethane showed no effect on liver triglyceride, SDH, and ALT levels (Aragno et 

al. 1992; Danni et al. 1992). Chronic exposure of rats to 25 mg/kg/day in food for 2 years did not result 

in abnormalities in liver function, as measured by transaminases and cholesterol values (Alumot et al. 

1976). In this chronic feeding study, the animals were not evaluated grossly or microscopically for liver 

lesions. There also were reported losses of 1,2-dichloroethane due to volatilization from the food; 

consequently, actual exposures would probably have been less than nominal exposures. No histological 

changes were observed in the liver of rats and mice that were administered #95 and #299 mg/kg/day, 

respectively, by gavage for #78 weeks (NCI 1978). 

Renal Effects. Acute renal damage resulting from ingestion of 1,2-dichloroethane has been observed 

in humans. Bleeding and hyperemia of the kidney were observed in an 18-year-old man who ingested a 

single dose of 714 mg/kg (Schönborn et al. 1970), and in a male hospital patient who died after 

accidentally ingesting a “small” quantity of 1,2-dichloroethane (Hubbs and Prusmack 1955). 

Observations upon microscopic examination included swelling, vacuolation, and degeneration of the renal 

tubule epithelial cells and sloughing of the glomerular capsular epithelium, and nearly complete loss of 

the bladder epithelium (Hubbs and Prusmack 1955). In one case study, renal damage that resulted from 

acute oral poisoning of a 25-year-old man was not considered severe or permanent, and the patient fully 
1,2-DICHLOROETHANE 77 

3. HEALTH EFFECTS 

recovered (Przezdziak and Bakula 1975). The amount of 1,2-dichloroethane ingested was not reported. 

However, individuals who died following ingestion of 15–30 mL of 1,2-dichloroethane had severe kidney 

damage, primarily in the form of diffuse renal necrosis (Hueper and Smith 1935; Lochhead and Close 

1951; Yodaiken and Babcock 1973). These are only crude estimates of ingested dose. 

Renal effects reported in animals were limited to increases in kidney weight and minimal-to-moderate 

histopathological changes after longer-term exposures. Relative kidney weight was increased without 

altered histology in rats that were treated with 75–90 mg/kg/day by gavage for 90 days (Daniel et al. 

1994; van Esch et al. 1977). An NTP (1991a) 13-week gavage study in rats found significant doserelated increases in kidney weight and kidney-to-body-weight ratio at 30–120 mg/kg/day in males and 

75–150 mg/kg/day in females (kidney weight was not measured in higher-dose animals because of 

mortality). Exposure to 1,2-dichloroethane in the drinking water for 13 weeks caused significant doserelated increases in kidney weight and kidney-to-body-weight ratio in rats at $58 mg/kg/day and mice at 

$244 mg/kg/day (NTP 1991a). The increase in kidney weight is considered to be an early-stage adverse 

effect in a known target tissue because renal histopathological changes occurred at higher doses. 

Histopathological examination of the animals in the drinking water study showed dose-related increased 

incidences of minimal-to-moderate renal regeneration in female rats at $102 mg/kg/day and male mice at 

$249 mg/kg/day. These changes are indicative of previous tubular injury with subsequent repair. More 

severe renal effects including karyomegaly, dilation, protein casts, and mineralization occurred in male 

mice exposed at 4,210 mg/kg/day. Based on these results, NTP (1991a) concluded that the kidney was a 

target organ for 1,2-dichloroethane in mice. Using a LOAEL of 58 mg/kg/day based on kidney effects, 

an intermediate oral MRL of 0.2 mg/kg/day was calculated as described in the footnote in Table 3-2 and 

in Appendix A. 

Other studies in animals failed to find evidence of kidney damage produced by 1,2-dichloroethane. Acute 

(10–14 days) gavage administration of up to 100 mg/kg/day did not result in treatment-related changes in 

kidney weight or in the incidence of gross or histopathological changes in the kidney in rats (Daniel et al. 

1994; van Esch et al. 1977). There were no changes in kidney weight in mice after administration of 

49 mg/kg/day by gavage for 14 days or exposure to 189 mg/kg/day in drinking water for 90 days 

(Munson et al. 1982), and kidney function, as measured by changes in serum levels of urea and uric acid, 

was normal in rats exposed to 25 mg/kg/day in food for 2 years (Alumot et al. 1976). Histological 

examination of the kidney was not performed in either of these studies. No histological changes were 

observed in the kidneys of rats and mice that were administered #95 and #299 mg/kg/day, respectively, 

by gavage for #78 weeks (NCI 1978). The discrepancy between the negative results of this bioassay and 
 

 

 

1,2-DICHLOROETHANE 78 

3. HEALTH EFFECTS 

the finding of kidney effects in the NTP (1991a) 13-week study may be related to animal strain. NTP 

(1991a) found compound-related renal changes in F344/N rats, whereas Osborne-Mendel rats were tested 

by NCI (1978); tests of Osborne-Mendel and Sprague-Dawley rats by NTP (1991a) were also negative. 

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

exposure to 1,2-dichloroethane. 

Endocrine function has not been evaluated in oral toxicity studies in animals. Histological examinations 

of endocrine system tissues were performed in several studies with essentially negative results, but lack of 

histopathology does not necessarily indicate that there were no functional endocrinologic changes. 

Histopathological examinations failed to detect changes in endocrine tissues in rats administered 

#100 mg/kg/day by gavage for 10 or 14 days (Daniel et al. 1994; van Esch et al. 1977), in rats 

administered #480 mg/kg/day by gavage for #90 days (Daniel et al. 1994; NTP 1991a; van Esch et al. 

1977), in rats and mice exposed to #492 and #4,210 mg/kg/day, respectively, in drinking water for 

#90 days (NTP 1991a), or in rats and mice exposed to #95 and #299 mg/kg/day, respectively, by gavage 

for #78 weeks (NCI 1978). The examinations in the NCI (1978) and NTP (1991a) studies were the most 

extensive and included tissues from the adrenal, pancreas, pituitary, thyroid, and parathyroid glands. 

The highest NOAEL values and all LOAEL values from each reliable study for endocrine effects in each 

species and duration category are recorded in Table 3-2 and plotted in Figure 3-2. 

Dermal Effects. No studies were located regarding dermal effects in humans after oral exposure to 

1,2-dichloroethane. 

Histological examinations showed no changes in the skin of rats administered #100 mg/kg/day by gavage 

for 14 days (Daniel et al. 1994), in rats administered #480 mg/kg/day by gavage for #90 days (Daniel et 

al. 1994; NTP 1991a; van Esch et al. 1977), or in rats and mice exposed to #492 and #4,210 mg/kg/day, 

respectively, in drinking water for #90 days (NTP 1991a). 

The highest NOAEL values and all LOAEL values from each reliable study for dermal effects in each 

species and duration category are recorded in Table 3-2 and plotted in Figure 3-2. 

Ocular Effects. No studies were located regarding ocular effects in humans after oral exposure to 

1,2-dichloroethane. 
 

1,2-DICHLOROETHANE 79 

3. HEALTH EFFECTS 

Ophthalmoscopic examinations showed no effects in rats that were treated with #150 mg/kg/day of 

1,2-dichloroethane by gavage in a 90-day study; the exams were performed prior to treatment and during 

the last week of the study (Daniel et al. 1994). Other 90-day studies similarly found no gross ocular 

changes in the eyes of rats treated with #480 mg/kg/day by gavage, or in rats and mice exposed to 

#492 and #4,210 mg/kg/day, respectively, in drinking water (NTP 1991a). 

The highest NOAEL values and all LOAEL values from each reliable study for ocular effects in each 

species and duration category are recorded in Table 3-2 and plotted in Figure 3-2. 

Body Weight Effects. No studies were located regarding effects on body weight in humans after oral 

exposure to 1,2-dichloroethane. 

Acute-duration animal studies found no effects on body weight in rats administered #100 mg/kg/day by 

gavage for 10 or 14 days (Daniel et al. 1994; van Esch et al. 1977), although gavage treatment with 

198 mg/kg/day (but not #158 mg/kg/day) for 14 days during pregnancy caused a 30% reduction in 

maternal body weight gain (Payan et al. 1995). Reduced growth (10–30% decreases in body weight gain) 

has been observed in animals following intermediate- and chronic-duration oral exposures, including rats 

administered $90 mg/kg/day by gavage for 90 days (Daniel et al. 1994; NTP 1991a; van Esch et al. 

1977), rats and mice exposed to $259 and 4,210 mg/kg/day, respectively, in drinking water for 90 days 

(NTP 1991a), and mice administered 299 mg/kg/day by gavage for #78 weeks (NCI 1978). No effect on 

body weight was seen in rats administered up to 95 mg/kg/day by gavage for 78 weeks (NCI 1978). 

The highest NOAEL values and all LOAEL values from each reliable study for body weight effects in 

each species and duration category are recorded in Table 3-2 and plotted in Figure 3-2. 

3.2.2.3 Immunological and Lymphoreticular Effects 

Limited information was located regarding immunological effects in humans after oral exposure to 

1,2-dichloroethane. Gross findings at autopsy of a male patient who ingested a “small” quantity of 

1,2-dichloroethane included a dark appearance of the spleen; hemorrhaging and congestion of the red 

pulp were observed microscopically (Hubbs and Prusmack 1955). 

Evidence from animal studies suggests that the immune system is a target of 1,2-dichloroethane toxicity 

after oral exposure. In 5-week-old mice exposed for 14 days by gavage to 4.9 and 49 mg/kg/day, there 
1,2-DICHLOROETHANE 80 

3. HEALTH EFFECTS 

was a significant dose-related reduction in humoral immunity (measured by immunoglobulin M [IgM] 

response to sheep erythrocytes), and a significant, but not dose-related, reduction in cell-mediated 

immunity (measured by delayed-type hypersensitivity response to sheep erythrocytes) (Munson et al. 

1982). In mice given 49 mg/kg/day, these effects were accompanied by a 30% decrease in total leukocyte 

number. 

Mice given drinking water containing up to 189 mg/kg/day of 1,2-dichloroethane for 90 days displayed 

no treatment-related effects on either the antibody-forming cell response or the delayed-type 

hypersensitivity response after immunization with sheep erythrocyte antigens (Munson et al. 1982). The 

authors suggested that the conflicting results in mice treated by gavage and those exposed to 1,2-dichloroethane in drinking water may reflect differences in compound administration and exposure duration, as 

discussed earlier (see the discussion of hematological effects in Section 3.2.2.2). No increase in the 

incidences of gross or histopathological changes were observed in the spleen, lymph nodes, or thymus in 

rats administered up to 100 mg/kg/day by gavage for 10 days (Daniel et al. 1994). 

Immune system function tests were not included in intermediate- and chronic-duration studies conducted 

by NTP (1991a). However, immune system tissues were examined for histopathological lesions in some 

of these studies. Thymic necrosis was observed in rats given $240 mg/kg/day of 1,2-dichloroethane by 

gavage #13 weeks (NTP 1991a). Because this lesion was found only in moribund animals, the study 

authors concluded that it was a result of generalized stress rather than a target organ effect. 1,2-Dichloroethane did not produce lesions in immune system tissues in rats and mice exposed to #492 mg/kg/day and 

#4,210 mg/kg/day, respectively, in drinking water for 13 weeks (NTP 1991a), in rats exposed by gavage 

to 150 mg/kg/day for 90 days (Daniel et al. 1994), or in rats and mice exposed to #95 and 

#299 mg/kg/day, respectively, by gavage for #78 weeks (NCI 1978). 

The highest NOAEL values and all LOAEL values from each reliable study for immunological effects in 

each species and duration category are recorded in Table 3-2 and plotted in Figure 3-2. 

3.2.2.4 Neurological Effects 

Neurological effects, such as central nervous system depression, have been reported in humans following 

acute oral intoxication with 1,2-dichloroethane (Hubbs and Prusmack 1955; Lochhead and Close 1951; 

Yodaiken and Babcock 1973). Morphological alterations in the nervous system were observed in patients 

who died of acute oral poisoning by 1,2-dichloroethane. These alterations included vascular disorders, 
1,2-DICHLOROETHANE 81 

3. HEALTH EFFECTS 

diffuse changes in cerebellar cells, parenchymatous changes in brain and spinal cord, myelin 

degeneration, and hyperemia, swelling, edema, and hemorrhage of the brain (Hubbs and Prusmack 1955; 

Hueper and Smith 1935; Lochhead and Close 1951). The morphological changes observed in the 

cerebellum may affect the coordination of muscular movements. 

Neurological effects have also been observed in animals exposed to 1,2-dichloroethane by ingestion. 

Clinical signs in rats exposed to $240 mg/kg/day by gavage for #13 weeks included tremors, salivation, 

emaciation, abnormal posture, ruffled fur, and dyspnea (NTP 1991a). Upon microscopic examination, 

mild necrotic lesions were observed in the cerebellum of rats dosed with 240 or 300 mg/kg/day. These 

lesions were not found in rats dosed with 480 mg/kg/day, but these rats all died after only 3 days of 

treatment and may not have had time to develop the lesion. Intermittent gavage exposure to 

90 mg/kg/day in female rats over a 90-day period induced a slight increase in relative brain weight (+8%) 

in female rats, but no clinical signs or histological changes in the brain or spinal cord were observed, and 

no neurological effects of any kind were seen in males at 90 mg/kg/day or in either sex at lower exposure 

levels (van Esch et al. 1977). Similarly, gavage administration of 75 and 150 mg/kg/day induced a 

significant increase in brain weight (+8 and +22%, respectively) in male rats without increases in the 

incidences of neurological clinical signs or lesions of the brain or sciatic nerve; no neurological effects of 

any kind were reported in females at $75 mg/kg/day or in either sex at lower exposure levels (Daniel et 

al. 1994). In the Daniel et al. (1994) study, the increase in relative brain weight may have been due to an 

observed dose-related decrease in body weight in the male rats, and may not necessarily be due to an 

actual change in brain weight; absolute organ weights were not reported. Exposure to 1,2-dichloroethane 

in the drinking water for 13 weeks did not produce increased brain weights, abnormal clinical signs, or 

lesions in nervous system tissues in rats (#492 mg/kg/day) or mice (#4,210 mg/kg/day) (NTP 1991a). 

(See the discussion of hematological effects in Section 3.2.2.2 regarding why effects that occur following 

bolus exposure might not occur following drinking water exposure). A 10-day gavage exposure to up to 

100 mg/kg/day did not induce an increase in brain weight or an increase in the incidences of gross or 

microscopic lesions in nervous system tissues of rats (Daniel et al. 1994), and a single gavage exposure to 

170 mg/kg in rats did not significantly alter neurotransmitter levels in various parts of the brain (Kanada 

et al. 1994). 

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

each species and duration category are recorded in Table 3-2 and plotted in Figure 3-2. 
1,2-DICHLOROETHANE 82 

3. HEALTH EFFECTS 

3.2.2.5 Reproductive Effects 

No studies were located regarding reproductive effects in humans after oral exposure to 1,2-dichloroethane. 

Studies in animals suggest that reproductive effects of 1,2-dichloroethane may be induced at oral doses 

that are maternally toxic. One-and two-generation reproduction studies showed no dose-dependent 

effects on fertility, gestation, viability, or lactation indices in mice exposed to doses of 5–50 mg/kg/day in 

drinking water for 24–49 weeks (Lane et al. 1982). Similarly, there were no effects on fertility indices 

(e.g., percentage pregnant, percent bearing litters, and litter size) in five pregnancies throughout a 2-year 

study during which rats ingested dietary doses of 21.3 or 42.5 mg/kg/day (Alumot et al. 1976). In a study 

using higher doses of 1,2-dichloroethane, rats that were treated with $198 mg/kg/day for 14 days during 

gestation showed 30% reduced body weight gain and dose-related increased percentages of nonsurviving 

implants per litter (resorptions plus dead fetuses) and resorption sites per litter (Payan et al. 1995). These 

effects did not occur at #158 mg/kg/day, and no changes in mean number of implantation sites or live 

fetuses per litter were observed. 

Histological examinations showed no changes in male or female reproductive tissues in rats administered 

#100 mg/kg/day by gavage for 10 days (Daniel et al. 1994), in rats administered #480 mg/kg/day by 

gavage for #90 days (Daniel et al. 1994; NTP 1991a; van Esch et al. 1977), in rats and mice exposed to 

#492 and #4,210 mg/kg/day, respectively, in drinking water for #13 weeks (NTP 1991a), or in rats and 

mice exposed to #95 and #299 mg/kg/day, respectively, by gavage for #78 weeks (NCI 1978). 

Reproductive performance was not evaluated in these studies. 

The highest NOAEL values from each reliable study for reproductive effects in each species and duration 

category are recorded in Table 3-2 and plotted in Figure 3-2. 

3.2.2.6 Developmental Effects 

No studies were located regarding developmental effects in humans exposed solely to 1,2-dichloroethane 

by ingestion. A cross-sectional epidemiologic study investigated whether elevated levels of routinely 

sampled organic contaminants in New Jersey public water systems, including 1,2-dichloroethane, were 

associated with increased prevalences of adverse birth outcomes (Bove 1996; Bove et al. 1995). The 

study population consisted of all live births and fetal deaths that occurred during 1985–1988 to residents 
1,2-DICHLOROETHANE 83 

3. HEALTH EFFECTS 

of 75 towns in a four-county area where some municipal water supplies were contaminated. A total of 

80,938 live births and 594 fetal deaths, excluding plural births, fetal deaths due to therapeutic abortions, 

and chromosomal anomalies, were studied. The comparison group comprised 52,334 (all) live births 

from the study population that had no birth defects and were not low birth weight, small for gestational 

age, or pre-term. A number of associations between various chemicals and birth outcomes were found, 

including a positive association between 1,2-dichloroethane and major cardiac defects for exposure levels 

>1 ppb compared to #1 ppb (OR=2.11). The odds ratio increased to 2.81 when exposure was 

recategorized as detected versus not detected. Croen et al. (1997) reported an increased crude odds ratio 

(OR=2.8; 95% CI 1.0–7.2; 14 exposed cases) for neural tube defects in offspring of residents within the 

census tract of NPL sites contaminated with 1,2-dichloroethane. The OR for residence within 1 mile of 

the NPL site was elevated, but was not significant (OR=1.7; 95% CI 0.8–3.6; 18 exposed cases). 

Although an association between 1,2-dichloroethane in drinking water and major birth defects was found 

in these epidemiological studies, concurrent mixed chemical exposures indicate that the results are only 

suggestive, do not establish a cause-and-effect relationship, and should be interpreted with caution. 

Primary routes of exposure in these epidemiological studies may have been both oral and inhalation 

(including inhalation of 1,2-dichloroethane volatilized from household water). 

Developmental toxicity studies in animals have not shown 1,2-dichloroethane to be fetotoxic or 

teratogenic following oral exposure, although indications of embryolethality at maternally toxic doses 

have been reported. Drinking water studies in mice found no increased incidences of fetal visceral and 

skeletal abnormalities following exposure to 50 mg/kg/day on gestation days 0–18 (Lane et al. 1982) or 

#510 mg/kg/day on gestation days 7–14 (Kavlock et al. 1979). Rats that were treated with 

$198 mg/kg/day by gavage on gestation days 6–20 showed 30% reduced body weight gain and some 

embryolethal effects (increased nonsurviving implants and resorption sites per litter), but no fetotoxicity 

or teratogenicity as indicated by fetal sex ratio, fetal body weight, and incidences of visceral and skeletal 

variations and malformations (Payan et al. 1995). The highest NOAEL values from each reliable study 

for developmental effects in mice after acute and intermediate exposure are recorded in Table 3-2 and 

plotted in Figure 3-2. 

3.2.2.7 Cancer 

Little information is available concerning the development of cancer in humans following ingestion of 

1,2-dichloroethane. Isacson et al. (1985) used indices of drinking water contamination to examine the 

relationship between cancer incidence and exposure to environmental pollutants in groundwater and 
1,2-DICHLOROETHANE 84 

3. HEALTH EFFECTS 

surface water samples. A statistically significant association was observed between the presence of 

1,2-dichloroethane in drinking water and an increased incidence of colon (p=0.009) and rectal (p=0.02) 

cancer in men aged 55 years or older. However, it is highly likely that the study population was 

concomitantly exposed to other chemicals. 

1,2-Dichloroethane was found to be carcinogenic in rats and mice that were exposed by gavage for up to 

78 weeks (NCI 1978). Statistically significant increases in multiple tumor types (malignant and benign) 

were noted in treated animals of both species. An increased incidence of fibromas of the subcutaneous 

tissue and hemangiosarcomas of the spleen, liver, pancreas, and adrenal gland (as well as other organs 

and tissues) occurred in male rats of both exposure groups (47 and 95 mg/kg/day). In the high-dose 

group (95 mg/kg/day), male rats had increased squamous cell carcinomas of the forestomach, and female 

rats had increased frequencies of adenocarcinomas and fibroadenomas of the mammary gland. In mice, 

the incidence of hepatocellular carcinomas and pulmonary adenomas increased in males given 

195 mg/kg/day. In female mice from both the 149- and 299-mg/kg/day exposure groups, there were 

increased incidences of pulmonary adenomas, adenocarcinomas of the mammary gland, and endometrial 

polyps and sarcomas. In conclusion, 1,2-dichloroethane administered by gavage produced tumors in rats 

and mice in tissues distant from the site of administration. The NCI (1978) study has a number of 

limitations including dosage adjustments throughout the course of the bioassay (because of the toxicity of 

1,2-dichloroethane), testing of other volatile organic chemicals in the same room, small numbers of 

concurrent controls, poor survival of treated animals, imprecise reporting of 1,2-dichloroethane purity, 

and use of a corn oil vehicle, which can alter the disposition of lipophilic compounds and the incidence of 

some spontaneous tumors. Despite these study limitations, it is prudent to consider the possibility of 

tumor induction when the chemical is administered via other routes and absorbed into systemic 

circulation as well. 

In another study, 1,2-dichloroethane was administered to B6C3F1 mice in their drinking water using a 

two-stage (initiation/promotion) treatment protocol; no increase in tumorigenicity was found (Klaunig et 

al. 1986). In this study, mice were initiated with diethylnitrosamine (DENA) for 4 weeks and 

subsequently treated with 159 or 475 mg/kg/day 1,2-dichloroethane for 52 weeks. 1,2-Dichloroethane 

did not increase the incidence of lung or liver tumors either alone or as a tumor promoter following 

DENA initiation. However, severe study limitations (including short duration, high liver-tumor incidence 

in untreated controls [20%] and in DENA-initiated [100%] mice after 52 weeks, lack of positive controls, 

and failure to specify the compound purity) invalidate any conclusions about the lack of carcinogenicity 

of 1,2-dichloroethane. A shorter-term initiation/promotion study in rats, based on the use of enzyme­
1,2-DICHLOROETHANE 85 

3. HEALTH EFFECTS 

altered liver foci as a marker for preneoplastic changes, also failed to confirm the carcinogenic potential 

of 1,2-dichloroethane (Milman et al. 1988), but was limited by use of a single dose level (100 mg/kg), 

short exposure duration (single dose in initiation study and 7 weeks in promotion study), and monitoring 

of an end point not firmly established as proof of carcinogenicity. 

In another two-stage oral cancer assay (Pott et al. 1998), a 16-week co-administration of 1,2-dichloroethane and arsenic (in drinking water) with vinyl chloride and trichloroethylene (administered by gavage) 

(all of which are chemicals commonly found at hazardous waste sites) produced dose-related inhibition of 

the promotion of preneoplastic hepatic lesions and bronchoalveolar hyperplasia and pulmonary adenomas 

in male Fisher 344 rats, after a 4-week initiation with a series of three broad-spectrum initiators. The 

drinking water concentrations of 1,2-dichloroethane ranged from 3 ppm (approximately 0.47 mg/kg/day) 

in the low exposure group (with relatively low levels of the other test substances) to 300 ppm 

(approximately 47 mg/kg/day) in the high exposure group (with relatively high levels of the other test 

substances). The study has limited usefulness for understanding lifetime risk of cancer from 

1,2-dichloroethane exposure because of co-exposure with other known carcinogens, the use of a short 

promotion exposure period (16 weeks), small numbers of test animals (15 per exposure group), and 

evaluation of effects to only one sex (males). 

CEL values from the chronic NCI (1978) study in rats and mice are recorded in Table 3-2 and plotted in 

Figure 3-2. 

EPA has derived a slope (potency) factor (q1*) of 0.091 (mg/kg/day)-1 for cancer risk associated with oral 

exposure to 1,2-dichloroethane based on the study by NCI (1978) in rats (IRIS 2001). This slope factor 

corresponds to a drinking water unit risk of 2.6x10-6 (μg/L)-1 and an inhalation unit risk of 

2.6x10-5 (μg/m3

)

-1. Based on this potency factor, oral doses of 1,2-dichloroethane associated with excess 

human lifetime cancer risks of 10-4, 10-5, 10-6, and 10-7 are 1x10-3, 1x10-4, 1x10-5, and 1x10-7 mg/kg/day, 

respectively. These risk levels correspond to one excess cancer death in 10,000, 100,000, 1 million, and 

10 million persons, respectively, and are derived based on the assumption that individuals are exposed 

continuously for their entire lifetime (estimated as 70 years) to these oral doses of 1,2-dichloroethane. 

The range of doses associated with excess lifetime cancer risks of 10-4 to 10-7 is plotted in Figure 3-2. The 

estimated excess cancer risks are upper-bound risks (i.e., the true risks are not likely to exceed the upperbound risk estimate and may be lower). 
 

 

1,2-DICHLOROETHANE 86 

3. HEALTH EFFECTS 

3.2.3 Dermal Exposure 

No studies were located regarding effects after dermal exposure to 1,2-dichloroethane in humans. In 

animals, ocular effects were produced by direct contact between the eye and 1,2-dichloroethane vapor in 

the air. Skin lesions and benign pulmonary tumors were reported in animals exposed to liquid 

1,2-dichloroethane dermally. 

3.2.3.1 Death 

No studies were located regarding death in humans or animals after dermal exposure to 1,2-dichloroethane. 

3.2.3.2 Systemic Effects 

No studies were located regarding respiratory, cardiovascular, gastrointestinal, hematological, 

musculoskeletal, hepatic, renal, endocrine, or body weight effects in humans or animals after dermal 

exposure to 1,2-dichloroethane. Dermal and ocular effects in animals dermally exposed to 

1,2-dichloroethane are discussed below. 

Dermal Effects. No studies were located regarding effects on the skin in humans after dermal 

exposure to 1,2-dichloroethane. 

A single animal study was located that investigated dermal effects following direct application of 

1,2-dichloroethane to the skin as a liquid. In guinea pigs, dermal exposure to unspecified amounts for 

4 hours applied to the skin under a cover slip resulted in skin changes, including karyopyknosis 

(shrinkage of cell nuclei), perinuclear edema, spongiosis, and junctional separation (Kronevi et al. 1981); 

however, only one dose was tested and no control data were presented. 

Ocular Effects. No studies were located regarding ocular effects in humans after dermal exposure to 

1,2-dichloroethane. 

Studies in animals reported direct-contact effects following exposure to 1,2-dichloroethane as a vapor in 

the air. Dogs exposed to 1,2-dichloroethane as a vapor in the air developed corneal opacity. This corneal 

clouding was observed in 3 dogs that died following intermittent exposure to 1,500 ppm for 6 days 
1,2-DICHLOROETHANE 87 

3. HEALTH EFFECTS 

(Heppel et al. 1945). Corneal opacity was not reported in other similarly exposed species studied by 

Heppel et al. (1945, 1946). However, lacrimation was reported in guinea pigs exposed to 1,500 ppm of 

1,2-dichloroethane vapor in air intermittently for 4 days (Heppel et al. 1945). 

No studies were located regarding the following health effects in humans or animals after dermal 

exposure to 1,2-dichloroethane: 

3.2.3.3 Immunological and Lymphoreticular Effects 

3.2.3.4 Neurological Effects 

3.2.3.5 Reproductive Effects 

3.2.3.6 Developmental Effects 

3.2.3.7 Cancer 

No studies were located regarding cancer in humans after dermal exposure to 1,2-dichloroethane. 

The carcinogenicity of 1,2-dichloroethane following dermal exposure has been evaluated in mice (Van 

Duuren et al. 1979). In this study, a statistically significant increase (p<0.0005) in pulmonary papillomas 

was observed in mice treated with 126 mg of 1,2-dichloroethane 3 times/week for 428–576 days. These 

results, which indicate a significant increase in benign tumors remote from the site of application, provide 

suggestive or supportive evidence that 1,2-dichloroethane is carcinogenic and that it can penetrate 

through the skin into the circulatory system. 

3.3 GENOTOXIC EFFECTS 

No studies were located regarding genotoxic effects in humans after inhalation exposure to 1,2-dichloroethane. Inhalation of 1,2-dichloroethane has produced genotoxic effects in animals. Exposure to 

1,000 ppm for 4 hours produced irreversible deoxyribonucleic acid (DNA) damage in mice as evidenced 

by single-stranded breaks in hepatocytes. This genetic damage was seen at a concentration that produced 

mortality in 80–100% of treated mice within 24 hours (Storer et al. 1984). A brief account of a mouse 

dominant lethal assay reported reduced impregnation rate, increased preimplantation loss, and increased 

ratio of total embryonic loss to number of corpora lutea compared to controls in female mice mated to 

males that had been exposed by inhalation to 200 ppm 1,2-dichloroethane for 4 hours/day for 2 weeks 

(Zhao et al. 1989). No effects were observed after exposure to 6.3 ppm for 2 weeks, nor at any 
1,2-DICHLOROETHANE 88 

3. HEALTH EFFECTS 

concentration after exposure durations of 1, 3, or 4 weeks. The reliability of the results is uncertain 

because of reporting deficiencies in the study design. In a study investigating the relationship between 

inhalation exposure to 1,2-dichloroethane and covalent binding to liver and lung DNA, female 

Fischer-344 rats were exposed either to 80 ppm of 1,2-dichloroethane for 4 hours ("constant-low" 

exposure) or 4,400 ppm for a few minutes ("peak" exposure) (Baertsch et al. 1991). The DNA covalent 

binding index was elevated, compared to controls, after both exposure scenarios. However, in both the 

liver and the lung, the effect was much greater (approximately 35 times greater) after peak exposure, 

suggesting that acute exposure to highly concentrated 1,2-dichloroethane may pose a greater genotoxic 

hazard than protracted low-level exposure. The results of this study support the hypothesis that toxicity 

of 1,2-dichloroethane is associated with saturation of mixed function oxidation (MFO) enzymes (see 

Section 3.4, Mechanisms of Action). Also consistent with this hypothesis is the fact that oral doses were 

more potent than comparable inhalation doses, and that a route-of-administration effect has been reported 

for 1,2-dichloroethane carcinogenicity. 

No studies were located regarding genotoxicity in humans after oral exposure to 1,2-dichloroethane, 

although oral exposure has produced genotoxic effects in animals. A single oral dose of 100 mg/kg of 

1,2-dichloroethane produced irreversible DNA damage in mice, as revealed by single-stranded breaks in 

hepatocytes (Storer et al. 1984). Hepatocytic DNA damage was also induced in female rats receiving two 

oral gavage doses of 1,2-dichloroethane (in corn oil) at 134 mg/kg each, but not in rats receiving two 

doses of 13.4 mg/kg (Kitchin and Brown 1994). A single oral dose of 150 mg/kg produced high levels of 

DNA binding in the liver of rats (Cheever et al. 1990). The level of binding produced was similar in rats 

that had previously been exposed via inhalation to 50 ppm of 1,2-dichloroethane vapor for 2 years, and in 

rats that had served as controls in the 2-year study. 

No studies were located regarding genotoxic effects in humans or animals after dermal exposure to 

1,2-dichloroethane. 

The results of in vivo genotoxicity studies by all routes of exposure are summarized in Table 3-3. As 

indicated in the table, the ability of 1,2-dichloroethane to bind DNA in rodents in vivo has been well 

established in the liver as well as in other organs such as the kidney and lung. DNA binding has been 

observed not only after inhalation and oral exposures, but also in rats (Banerjee 1988; Prodi et al. 1986) 

and mice (Banerjee 1988; Hellman and Brandt 1986; Prodi et al. 1986) administered a single 

intraperitoneal injection of 1,2-dichloroethane at dose levels as low as 6.35 μmol/kg (0.00635 mg/kg) 

(Prodi et al. 1986). Actual structural damage to DNA, in the form of single-stranded breaks and 
Table 3-3. Genotoxicity of 1,2-Dichloroethane In Vivo 

Species (test system) End point Results Reference Mammalian assays: 

Mouse/spot test Mouse bone marrow Mouse Mouse Mouse, Eμ-PIM-1 Mouse liver, kidney, lung, and stomach Mouse forestomach and kidney Mouse liver Rat liver, kidney, lung, and stomach Rat liver and kidney Rat liver and lung Rat liver Rat liver Mouse liver Mouse liver

 Mouse liver, kidney, bladder, lung, brain, bone marrow Insect assays: 

Drosophila melanogaster//somatic mutation D. melanogaster/somatic mutation 

D. melanogaster/somatic mutation D. melanogaster/somatic mutation D. melanogaster/somatic mutation 

D. melanogaster/sex-linked recessive 

D. melanogaster/sex-linked recessive D. melanogaster/recessive lethal 

D. melanogaster D. melanogaster/chromosome loss 

D. melanogaster 

Gene mutation (+)

Sister chromatid exchange +Micronuclei –Micronuclei –Micronuclei –DNA binding +DNA binding +DNA binding +DNA binding +DNA binding +DNA binding +DNA binding +DNA binding +DNA damage + DNA damage +DNA damage + Gene mutation +Gene mutation +Gene mutation +Gene mutation +Gene mutation +Gene mutation +Gene mutation +Gene mutation + Chromosomal recombination (+)Chromosomal aberration +DNA binding + 

Gocke et al. 1983 Giri and Hee 1988 Jenssen and Ramal 198Sasaki et al. 1994 Armstrong and Galloway Prodi et al. 1986 Hellman and Brandt 198Banerjee 1988 Prodi et al. 1986 Inskeep et al. 1986 Baertsch et al. 1991 Banerjee 1988 Cheever et al. 1990 Storer and Conolly 1983Storer et al. 1984 Taningher et al. 1991 Sasaki et al. 1998 Nylander et al. 1978 Romert et al. 1990 Kramers et al. 1991 Ballering et al. 1994 Vogal and Nivard 1993 King et al. 1979 Kramers et al. 1991 Ballering et al. 1993 Rodriguez-Arnaiz 1998 Ballering et al. 1993 Fossett et al. 1995 
Table 3-3. Genotoxicity of 1,2-Dichloroethane In Vivo (continued) 

Species (test system) End point Results Reference Host-mediated assays: 

Escherichia coli K12/343/113 mouse host-mediated assay 

Gene mutation – King et al. 1979 

– = negative result; + = positive result; (+) = weakly positive result; DNA = deoxyribonucleic acidtable 3-3 
 

1,2-DICHLOROETHANE 91 

3. HEALTH EFFECTS 

unwinding of the DNA molecule, has also been demonstrated in mice after single intraperitoneal 

injections of 45–360 mg/kg (Sasaki et al. 1998; Storer and Conolly 1983, 1985; Storer et al. 1984; 

Taningher et al. 1991). In one study, DNA binding was associated with decreased rates of DNA synthesis 

and transcription (Banerjee 1988). However, the results of this study are questionable. Genotoxicity 

assays for clastogenic effects obtained mixed results, with a positive effect on sister chromatid exchange 

(believed to be caused by strand breakage) in mouse bone marrow cells of mice administered a single 

intraperitoneal injection of up to 16 mg/kg, but no effect on micronucleus formation in mice after 

14 weeks of daily gavage administrations of up to 300 mg/kg/day or in mice after a single intraperitoneal 

injection of between 45–400 mg/kg (Jenssen and Ramel 1980; King et al. 1979; Sasaki et al. 1994). The 

only in vivo assay for mutagenicity in mammalian cells produced only a marginal response after a single 

intraperitoneal injection of an unreported dose. However, there is abundant evidence that 1,2-dichloroethane produces both somatic and sex-linked recessive lethal mutations in Drosophila melanogaster in 

vivo. 

The results of in vitro genotoxicity studies are presented in Table 3-4. The evidence from these studies 

overwhelmingly indicates that 1,2-dichloroethane is capable of interacting with DNA to produce 

genotoxic effects in vitro. Results were positive in assays for point mutations in human cells, animal 

cells, and bacteria, unscheduled DNA synthesis (i.e., DNA repair activity) in human and animal cells, 

DNA binding in animal cells, and mitotic segregation aberrations leading to aneuploidy in fungi. The 

results in bacterial mutagenicity assays suggest that 1,2-dichloroethane is a very weak, direct-acting 

mutagen that can be activated to a more effective species by glutathione and glutathione S-transferases 

(DeMarini and Brooks 1992). The presence of an exogenous mammalian metabolic system was not 

required, but increased mutagenic activity was observed in tests with a metabolic activation system 

supplemented with glutathione. Mutagenicity was increased in TA100 strain Salmonella typhimurium 

expressing the alpha class of human glutathione S-transferase via regulatable tac promoter expression, but 

not in bacteria expressing the pi class of human glutathione S-transferase (Simula et al. 1993). 

S-(Chloroethyl)-cysteine, an analog of the proposed intermediate product of the conjugation of 

1,2-dichloroethane with glutathione, was a potent inducer of unscheduled DNA synthesis and 

micronucleus formation in mammalian cells in vitro (Vamvakas et al. 1988, 1989). S-(2-Chloroethyl)­

glutathione itself was found to be a potent mutagen in S. typhimurium. Although it produced only 

intermediate levels of alkylation, the results indicate that the guanyl adduct that is formed appears to be 

unusually mutagenic (Humphreys et al. 1990). 1,2-Dichloroethane was found to be nonmutagenic in 

somatic cells and mature spermatozoa in D. melanogaster, further suggesting the lack of genotoxicity 

through a direct mechanism (Ballering et al. 1993). 
Table 3-4. Genotoxicity of 1,2-Dichloroethane In Vitro 

Results 

With Without 

Species (test system) End point activation activation Referen

Prokaryotic organisms: 

Salmonella typhimurium S. typhimurium S. typhimurium S. typhimurium S. typhimurium S. typhimurium S. typhimurium S. typhimurium S. typhimurium S. typhimurium S. typhimurium S. typhimurium S. typhimurium/spot test S. typhimurium/spot test S. typhimurium/Ara test (standard) S. typhimurium/Ara test (liquid) Escherichia coli K12/343/113 E. coli WP2 

E. coli WP2 E. coli Pol A Bacillus subtilis/rec-assay 

Gene mutation Gene mutation Gene mutation Gene mutation Gene mutation Gene mutation Gene mutation Gene mutation Gene mutation Gene mutation Gene mutation Gene mutation Gene mutation Gene mutation Gene mutation Gene mutation Gene mutation Gene mutation Gene mutation DNA damage DNA damage

 + + + + + + + + + – No data No data No data No data + (+) – No data – No data No data

 + + + + + + No data – – – + + (+) – – (+) – (+) – (+) – 

Milman eBarber et Kanada aNestmanRannug eVan BladRannug aCheh et aMoriya et King et aThier et aSimula eBrem et aBuijs et aRoldan-ARoldan-AKing et aHemminkMoriya et Brem et aKanada a
Table 3-4. Genotoxicity of 1,2-Dichloroethane In Vitro (continued) 

Results 

With Without 

Species (test system) End point activation activation Referen

Eukaryotic organisms: Fungi: 

Aspergillus nidulans A. nidulans A. nidulans 

 Animal cells: 

Hamster CHO/HGPRTHamster Chinese SP5Rat hepatocytesMouse hepatocytesMouse liver DNACalf thymus DNASalmon sperm DNAMouse BALB/c-3T3 

Human cells: 

Human lymphoblasts AHH-1Human lymphoblasts TK6Human lymphoblasts AHH-1Human lymphoblasts MCL-5Human lymphoblasts h2E1Human embryo epithelial-like EUE cellsHuman peripheral lymphocytesHuman peripheral lymphocytesHuman peripheral lymphocytes

Gene mutation Mitotic segregation aberrations Aneuploidy induction Gene mutation Intrachromosomal recombination Unscheduled DNA synthesis Unscheduled DNA synthesis DNA binding DNA binding DNA binding Cell transformationGene mutation Gene mutation Micronuclei Micronuclei Micronuclei Gene mutation Unscheduled DNA synthesis Micronuclei DNA damage 

No data No data No data + – No data No data + + + No data No data No data No data No data No data No data + – –

 – + + (+) No data + + No data No data – – + + + + + + – + + 

Crebelli aCrebelli eCrebelli eTan and Zhang anWilliams Milman eBanerjee Prodi et aBanerjee 1979; BaMilmann Crespi et Crespi et Doherty eDoherty eDoherty eFerreri et Perocco Tafazoli eTafazoli e

– = negative result; + = positive result; (+) = weakly positive result; DNA = deoxyribonucleic acid 
1,2-DICHLOROETHANE 94 

3. HEALTH EFFECTS 

3.4 TOXICOKINETICS 

1,2-Dichloroethane is well absorbed through the lungs following inhalation exposure, the gastrointestinal 

tract following oral exposure, and the skin following dermal exposure in humans. In animal studies, 

equilibrium blood concentrations of 1,2-dichloroethane were obtained 2–3 hours after inhalation 

exposure, 15–60 minutes after oral exposure, and 1–2 hours after aqueous dermal exposure. Absorption 

probably occurs by passive diffusion for all three routes of exposure. Upon absorption, 1,2-dichloroethane is widely distributed within the body. Experiments in animals exposed orally or by inhalation 

showed that the highest concentrations of 1,2-dichloroethane (7–17 times that of the blood) were found in 

adipose tissue. The liver and lung contained lower equilibrium levels of 1,2-dichloroethane than the 

blood. 

1,2-Dichloroethane is readily metabolized in the body. The primary metabolic pathways for this chemical 

are MFO and glutathione conjugation. Oxidation products include chloroacetaldehyde, 2-chloroethanol, 

and 2-chloroacetic acid. MFO metabolism of 1,2-dichloroethane appears to be saturable at oral gavage 

doses $25 mg/kg and inhalation concentrations of $150 ppm (.500 mg/kg), both of which correspond to 

blood levels of 5–10 μg/mL. Glutathione conjugation becomes relatively more important at larger doses, 

and increased metabolism by this pathway may be responsible for the toxic effects noted at these high 

doses. 

Excretion of 1,2-dichloroethane and metabolites is rapid; in animal studies, excretion was essentially 

complete 48 hours after acute exposure. Following inhalation exposure to labeled 1,2-dichloroethane, 

excretion of 1,2-dichloroethane was primarily in the form of metabolites (thiodiglycolic acid and 

thiodiglycolic acid sulfoxide) in the urine (84%), and as carbon dioxide (CO2) in the exhaled air (7%). 

Following oral exposure to labeled 1,2-dichloroethane, the amount of radioactivity excreted by these 

routes was reduced, and a large percentage of the dose (29%) was excreted as unchanged 1,2-dichloroethane in the exhaled air. The increased exhalation of unchanged 1,2-dichloroethane may reflect the 

saturation of biotransformation enzymes. 
1,2-DICHLOROETHANE 95 

3. HEALTH EFFECTS 

3.4.1 Absorption 

3.4.1.1 Inhalation Exposure 

1,2-Dichloroethane is readily absorbed through the lungs following inhalation exposure in both humans 

and experimental animals. This is expected, based on 1,2-dichloroethane's high vapor pressure and high 

serum/air partition coefficient. Thus, absorption occurs most likely via passive diffusion across alveolar 

membranes. Nursing women exposed to 15.6 ppm of 1,2-dichloroethane in the workplace air (with 

concurrent dermal exposure) accumulated the chemical in breast milk (Urusova 1953). The concentration 

of the chemical in milk gradually increased, reaching the maximum level 1 hour after work ended, 

although the validity of the results could not be assessed because of a lack of sufficient detail in reported 

methods and because the sample size was not provided. EPA (1980a) also found 1,2-dichloroethane in 

the milk of lactating women. These results indicate that 1,2-dichloroethane is absorbed through the lungs 

by humans and accumulates (because of its high lipid-water partition coefficient) in the breast milk of 

nursing women. Concurrent levels of 1,2-dichloroethane in blood were not measured (EPA 1980a; 

Urusova 1953). 

Nouchi et al. (1984) reported a fatal case of 1,2-dichloroethane poisoning in a man exposed to 

1,2-dichloroethane vapors for approximately 30 minutes in an enclosed space (concentration in air not 

specified), providing further evidence that this chemical is readily absorbed through the lungs by humans. 

However, adverse effects were seen at 20 hours postexposure, prompting the authors to suggest that the 

formation of reactive metabolites is a necessary first step in the expression of 1,2-dichloroethane-induced 

toxicity. An alternative explanation is that the 1,2-dichloroethane is, in part, slowly released from adipose 

tissue or other compartments after an initial rapid release (see Section 3.4.3) 

The rapid absorption of 1,2-dichloroethane following inhalation exposure has also been demonstrated in 

experimental animals. Reitz et al. (1980, 1982) found that peak blood levels were constant 1–2 hours 

after the onset of a 6-hour inhalation exposure to 150 ppm of 1,2-dichloroethane in rats. The plateau 

concentration in blood was approximately 8 μg/mL and was reached within 2 hours. Similar results were 

obtained by Spreafico et al. (1980) at inhalation exposures of 50 ppm of 1,2-dichloroethane. However, at 

250 ppm of 1,2-dichloroethane, equilibrium was not achieved until 3 hours from the start of exposure. It 

is likely that as the concentration of inspired 1,2-dichloroethane increases, the time required to reach an 

equilibrium concentration of 1,2-dichloroethane in the blood also increases. In rats that had been exposed 

to 1,2-dichloroethane vapor (50 ppm) intermittently for 2 years, blood levels of 1,2-dichloroethane 
1,2-DICHLOROETHANE 96 

3. HEALTH EFFECTS 

15 minutes after the end of a 7-hour exposure to 50 ppm were 0.26–0.28 μg/mL (Cheever et al. 1990). 

Blood levels were not increased, but rather only slightly reduced after an additional 2 hours, which 

suggests that equilibrium had been reached during the exposure period. 

3.4.1.2 Oral Exposure 

No studies were located regarding absorption in humans following oral exposure to 1,2-dichloroethane. 

However, it can be inferred from case studies, which described toxic effects (including death) subsequent 

to accidental (Hueper and Smith 1935) or intentional (Lochhead and Close 1951; Yodaiken and Babcock 

1973) ingestion of 1,2-dichloroethane by humans, that 1,2-dichloroethane is rapidly absorbed into the 

systemic circulation following exposure by the oral route. 1,2-Dichloroethane is lipophilic and is 

expected, therefore, to be absorbed largely via passive diffusion across the mucosal membranes of the 

gastrointestinal tract. 

Studies in experimental animals indicate that the oral absorption of 1,2-dichloroethane is rapid, complete, 

and essentially linear (Reitz et al. 1980, 1982; Spreafico et al. 1980). Reitz et al. (1982) reported that 

peak blood levels of 1,2-dichloroethane were reached within 15 minutes after oral administration of 

150 mg/kg by gavage in corn oil to male Osborne-Mendel rats, attesting to the rapid nature of oral 

absorption. These investigators reported complete recovery of orally administered radioactivity (from 

[

14C]-1,2-dichloroethane) in exhaled air, urine, and carcass, thereby demonstrating that absorption of 

1,2-dichloroethane from the gastrointestinal tract of rats is virtually complete (Reitz et al. 1980). The 

percentage of recovered radioactivity found in the feces following inhalation or oral exposure to 

[

14C]-1,2-dichloroethane was 1.7–2.1%; 7.0–7.7% of the recovered dose was found in the expired air 

following exposure by either route (Reitz et al. 1980). This implies that at least 90% of the inhaled or 

orally administered 1,2-dichloroethane was absorbed. 

Data reported by Spreafico et al. (1980) supported the observation that absorption of 1,2-dichloroethane is 

rapid and complete. In Sprague-Dawley rats, peak blood levels were achieved within 30–60 minutes of 

oral administration at doses of 25, 50, and 150 mg/kg in corn oil. One-half of the low dose was absorbed 

within 3.3 minutes, and one-half of the high dose was absorbed within 6.4 minutes (Spreafico et al. 1980). 

Peak blood levels achieved were proportional to the dose administered, thus providing evidence that 

1,2-dichloroethane is absorbed by passive transport across the gastrointestinal tract. Furthermore, 

comparison of blood levels attained after intravenous (i.e., reflective of 100% absorption) and oral 
1,2-DICHLOROETHANE 97 

3. HEALTH EFFECTS 

administration of 1,2-dichloroethane in rats indicates that oral absorption is 100%, if first-pass effects 

through the liver and lung are taken into consideration (Spreafico et al. 1980). 

The vehicle used in oral administration studies appears to play a role in the time course of absorption. 

Withey et al. (1983) found that 1,2-dichloroethane is absorbed more readily by the gastrointestinal tract 

when administered in water than in corn oil. Peak blood concentrations of 1,2-dichloroethane were about 

four times higher following oral administration in water than when given in corn oil. This may relate to 

higher solubility vehicles regarding the absorption of xenobiotics. Furthermore, the time taken to reach 

peak levels was approximately three times longer when administered in corn oil, compared to water. This 

may have important implications with regard to human exposure to 1,2-dichloroethane. Since animal data 

and the available information in humans indicate that oral absorption of 1,2-dichloroethane in aqueous 

solutions is rapid and complete, ingestion of water contaminated with high levels of 1,2-dichloroethane is 

of particular concern and could result in adverse health effects in humans. However, no unequivocal 

information was available concerning health effects in humans after long-term exposure to low levels of 

1,2-dichloroethane in drinking water. 

3.4.1.3 Dermal Exposure 

Urusova (1953) reported a gradual increase in the concentration of 1,2-dichloroethane in the breast milk 

of nursing women following both dermal and inhalation exposure to 1,2-dichloroethane at the workplace. 

Maximum levels were reached within 1 hour (2.8 mg/100 mL of milk) after skin contact and decreased 

over time. Eighteen hours later, the concentration of 1,2-dichloroethane in milk ranged between 

0.195 and 0.63 mg/100 mL of milk. The findings of Urusova (1953) indicate that percutaneous 

absorption via contact with contaminated water or the chemical itself may be a significant route of 

exposure to 1,2-dichloroethane in humans. No details of analytical methodology were reported, and the 

sample size was not provided, and thus, the validity of these results cannot be assessed. 

Studies in animals have shown that 1,2-dichloroethane is well absorbed through the skin following dermal 

exposure. Male rats exposed to 2 mL of 1,2-dichloroethane under cover on a shaved area of the back had 

blood 1,2-dichloroethane levels of 25 μg/mL after 30 minutes (Morgan et al. 1991). After 24 hours, 

blood levels were 135 μg/mL and a total of 1.08 mL had been absorbed. The continued build-up of blood 

levels throughout the 24-hour exposure period shows that the rate of absorption exceeded that of 

distribution and elimination throughout this entire period. When the experiment was repeated using 

solutions of 1,2-dichloroethane in water, blood levels peaked after 1–2 hours (at concentrations of 
1,2-DICHLOROETHANE 98 

3. HEALTH EFFECTS 

0.35–1.4 μg/mL, depending on degree of saturation of the applied solution) and then declined to control 

levels within 24 hours. Analysis of the aqueous solutions remaining in the exposure chamber after 

24 hours showed that they contained <1% of the initial 1,2-dichloroethane concentration. This result 

suggests that 1,2-dichloroethane in water was rapidly and completely absorbed from solution, thus 

allowing elimination processes to reduce blood concentration to control levels within the 24-hour 

exposure period. 1,2-Dichloroethane was among the best absorbed of the 14 volatile organic compounds 

tested in this experiment. 

Supporting data for the time course of absorption following neat exposure were obtained by Jakobson et 

al. (1982), who studied the dermal absorption of 1,2-dichloroethane in anesthetized guinea pigs. Blood 

concentrations rose rapidly during the first half-hour after application, followed by steadily increasing 

blood levels throughout the 12-hour exposure period. Tsuruta (1975) estimated the rate of percutaneous 

absorption of 1,2-dichloroethane. After a 15-minute exposure, the absorption rate through the abdominal 

skin of mice was 480 nmol/minute/cm2

. In contrast to the results of Morgan et al. (1991), comparisons of 

this absorption rate with those of other chlorinated hydrocarbons tested in the same study did not support 

the conclusion that 1,2-dichloroethane is among the more rapidly absorbed of these chemicals. 

3.4.2 Distribution 

3.4.2.1 Inhalation Exposure 

1,2-Dichloroethane was detected in the breath (14.3 ppm) and breast milk (0.54–0.64 mg % [per 

100 mL]) of nursing mothers 1 hour after leaving factory premises containing 15.6 ppm 1,2-dichloroethane in the air (Urusova 1953). This observation suggests a rapid distribution of 1,2-dichloroethane in 

humans following inhalation exposure. 

The distribution of 1,2-dichloroethane in rats following a 6-hour inhalation exposure to 50 or 250 ppm 

occurred readily throughout body tissues; levels achieved in tissues were dose-dependent (Spreafico et al. 

1980). The investigators measured 1,2-dichloroethane in blood, liver, lung, and fat, and found that blood 

and tissue levels reached equilibrium by 2 hours after exposure to 50 ppm and 3 hours after exposure to 

250 ppm. Concentrations of 1,2-dichloroethane in liver and lung were lower than those in blood. The 

highest concentration of 1,2-dichloroethane was found in fat (8–9 times that seen in blood). 

1,2-Dichloroethane was found in maternal blood (83.6±20.2 mg %), placental tissue (43.0±9.6 mg %), 

amniotic fluid (55.5±11.1 mg %), and fetal tissue (50.6±11.5 mg %) after inhalation exposure of female 
1,2-DICHLOROETHANE 99 

3. HEALTH EFFECTS 

rats to 247±10 ppm 1,2-dichloroethane during pregnancy (Vozovaya 1977), but the reliability of the data 

is unclear. The geometric mean concentration of 1,2-dichloroethane in maternal blood and in fetuses of 

rats that inhaled 150–2,000 ppm for 5 hours increased linearly with increasing exposure level (Withey 

and Karpinski 1985), indicating transplacental distribution of 1,2-dichloroethane. The slope and intercept 

of the relation between fetal concentration of 1,2-dichloroethane (μg/g) and exposure level were 

0.035 and -3.95, respectively, and for concentration in maternal blood (μg/g), they were 0.092 and -10.4, 

respectively. However, details of the methods used to detect 1,2-dichloroethane and quantify its 

concentration in tissues were not provided in Withey and Karpinski (1985), so the validity of the results 

cannot be confirmed. 

3.4.2.2 Oral Exposure 

No studies were located regarding distribution in humans after oral exposure to 1,2-dichloroethane. 

However, the wide variety of effects noted in humans following oral exposure suggest a wide distribution. 

1,2-Dichloroethane was distributed readily throughout the body following oral administration of single 

doses to rats (Spreafico et al. 1980). As was seen following inhalation exposure, peak tissue levels were 

dose-dependent. Spreafico et al. (1980) reported that 1,2-dichloroethane absorbed through the 

gastrointestinal tract reached peak concentrations in the liver within 10 minutes. Again, equilibrium 

levels in liver and lung (achieved by 2 hours postexposure) were lower than in blood, while levels in fat 

were 7–17 times greater than in blood. This difference in tissue levels decreased with increasing dose. 

Thus, there is little difference between oral and inhalation exposure with regard to tissue distribution in 

animals, and specific target organ toxicity cannot be explained by differential distribution of 1,2-dichloroethane. 

Payan et al. (1995) evaluated [14C]-1,2-dichloroethane distribution in maternal rats following a single 

bolus dose of approximately 160 mg/kg on gestation day 12. At 1 hour after exposure, 50% of the orally 

administered dose was in gastrointestinal tract tissues, falling to 0.2% of the administered dose by 

48 hours after exposure, while less than 1% was accounted for in the feces. Aside from the absorptive 

tissues, the liver and kidney accounted for most of the distributed radioactivity throughout the 48-hour 

postexposure observation period, although adipose tissue and brain and spinal cord tissues, possible sites 

of accumulation, were not included in the evaluation. The highest tissue concentrations were found in the 

liver, ovary, and kidney. Transplacental distribution of radiocarbon was demonstrated by the presence of 

radioactivity in the developing conceptus at 1 hour postexposure, with the highest amount in the 
1,2-DICHLOROETHANE 100 

3. HEALTH EFFECTS 

conceptus (0.057% of administered dose) occurring at approximately 4 hours postexposure. At 48 hours 

postexposure, most of the residual radioactivity was located in the liver (0.215% of administered dose). 

When 160 mg/kg was administered on gestation day 18, the pattern of distribution was similar, except 

greater accumulation occurred in the developing fetus and placenta. At 48 hours postexposure (the 

20th day of gestation), the majority of residual radioactivity burden was located in the fetus (0.167% of 

administered dose) and the liver (0.156% of administered dose). 

Spreafico et al. (1980) studied the distribution of 1,2-dichloroethane in rats following repeated oral 

administration (11 daily doses). They demonstrated that there was no difference between blood or tissue 

levels following either single or repeated exposure. This finding suggests that bioaccumulation of 

1,2-dichloroethane does not occur with repeated oral exposure. 

3.4.2.3 Dermal Exposure 

1,2-Dichloroethane was detected in the breast milk of nursing mothers following dermal exposure (with 

probable concurrent inhalation exposure) to liquid 1,2-dichloroethane at the workplace (Urusova 1953). 

The concentration in milk gradually increased, with the maximum level (2.8 mg %) reached 1 hour after 

work ended. Eighteen hours later, the levels in milk ranged from 0.195 to 0.63 mg %. This study did not 

report the dermal exposure concentration of 1,2-dichloroethane. Because of the lack of details on 

methodology, the validity of these findings cannot be assessed. 

No studies regarding distribution in animals following dermal exposure to 1,2-dichloroethane were 

located. Since the tissue distribution of this chemical did not appear to be route-dependent after either 

inhalation or oral exposure, and since it is well absorbed through the skin, the distribution pattern of 

1,2-dichloroethane following percutaneous application may possibly resemble that observed following 

exposure via other routes. 

3.4.2.4 Other Routes of Exposure 

No studies were located regarding distribution in humans after parenteral exposure to 1,2-dichloroethane. 

Mice exposed to radiolabeled 1,2-dichloroethane by a single intravenous injection had high levels of 

tightly bound radioactivity in the nasal mucosa and tracheo-bronchial epithelium within 1 minute of 

exposure; these levels persisted throughout the 4-day observation period (Brittebo et al. 1989). Lower 
1,2-DICHLOROETHANE 101 

3. HEALTH EFFECTS 

levels of radioactivity were bound to epithelia of the upper alimentary tract, eyelid, and vagina, as well as 

the liver, kidney, adrenal cortex, and submaxillary gland. The bound radioactivity was considered to 

represent nonvolatile reactive metabolites formed in the tissues where it was found. A study of tissue 

kinetics of 1,2-dichloroethane in rats after a single intravenous dose of 15 mg/kg reported preferential 

initial distribution to fat (Withey and Collins 1980) and first-order elimination from each tissue studied 

(except blood). The estimated initial concentration in fat was 36.9 μg/g, while for other soft tissues 

(including heart, lung, liver, spleen, kidney, and brain), the initial concentrations were relatively uniform, 

with estimates ranging from 4.2 to 9.2 μg/g. The study also showed that distributed 1,2-dichloroethane 

remained in fat longer than in other soft tissues, as indicated by a lower estimated elimination coefficient 

in fat (0.0088 min-1) relative to other tissues (ranged from 0.0226 to 0.0514 minute-1). 

3.4.3 Metabolism 

No studies regarding metabolism in humans following inhalation, oral, or dermal exposure to 

1,2-dichloroethane were located. The biotransformation of 1,2-dichloroethane has been studied 

extensively in rats and mice both in vivo and in vitro. Proposed metabolic pathways for 1,2-dichloroethane are shown in Figure 3-3. The results of the in vivo studies indicate that 1,2-dichloroethane is 

readily metabolized in the body, the primary route of biotransformation involves conjugation with 

glutathione to yield nonvolatile urinary metabolites, and the enzymes involved in the biotransformation of 

1,2-dichloroethane are saturable at approximately 25 mg/kg/day (gavage) and 150 ppm (inhalation) 

(D'Souza et al. 1988; Reitz et al. 1982). Metabolic saturation appears to occur sooner after oral (gavage) 

administration than after inhalation exposure. This will be discussed further below. A proposed 

physiological pharmacokinetic model explains the route-of-exposure difference in quantifying the amount 

of 1,2-dichloroethane-glutathione conjugate produced in target organs after oral and inhalation exposures 

(D'Souza et al. 1987, 1988). 

No studies were located regarding metabolism specifically in children. However, the expression of 

certain enzymes is known to be developmentally regulated. An N-acetyltransferase (NAT) is thought to 

be involved in 1,2-dichloroethane metabolism at a step subsequent to a glutathione (GSH) conjugation 

(see Figure 3-3). There are two NATs (NAT1 and NAT2) that are expressed in humans (Parkinson 1996) 

and one, NAT2, is known to be developmentally regulated (Leeder and Kearns 1997). Some NAT2 

activity is present in the fetus at 16 weeks. Activity is low in virtually 100% of infants, and reaches adult 

activity at 1 to 3 years of age (Leeder and Kearns 1997). 
Cytochrome P 450 

1,2 O -Dichloroethane Glutathione-S-transferase 2.NADPH 

GSH 

Cl 

Cl 

Cl Cl 

OH GS 

S-(2 -Chloroethyl)-glutathione 

gem-Chlorohydrin (Half-Mustard) GSH 

CH2=CH2 

Cellular ethene 

O NADH OH + macromolecular GSSG, HCl Cl adducts NAD+ Cl Cl + GS 

2 -Chloroacetaldehyde 2 -Chloroethanol 

+ 

Cl 

Aldehyde
 

dehydrogenase
 GSH -OH 

NAD(P)H
 

OH
 OH O 

Cl GS GS

O S-(2 S-(2-Hydroxyethyl)-glutathione -Formylmethyl)-glutathione 

2 -Chloroacetic acid 

Aldehyde 

NAD(P)H GSH dehydrogenase 

Urine metabolites 

Glutathione episulfonium ion 

Protein 

DNA 

RNA 

GSH 

Cellular 

macromolecular 

adducts 

OH SG 

GS GS 

O S,S' -Ethene bisglutathione 

S-Carboxymethyl glutathione 

y-Glutamyl * transpeptidase 

H2O 

O S,S '-Ethene bis-L-cysteine
 

HO
 OH
 

N
 S 

Urine metabolites 

O H NH2 O 

S-Carboxymethyl-L-cysteinylglycine 

Dipeptidase H2O 

O O HO OH OH OH Acetyl CoA HO S S

HO S N-Acetyltransferase O O HN CH3 O NH2 O Thiodiacetic acid 

S-Carboxymethyl-L-cysteine (thiodiglycolic acid) 

O 

N-Acetyl-S-carboxymethyl-L-cysteine 

Derived from NTP 1991a 

1,2-DICHLOROETHANE 102 

3. HEALTH EFFECTS 

Figure 3-3. Proposed Pathways for 1,2-Dichloroethane Metabolism* 
1,2-DICHLOROETHANE 103 

3. HEALTH EFFECTS 

3.4.3.1 Inhalation Exposure 

Reitz et al. (1982) studied the metabolism of 1,2-dichloroethane in male rats following a 6-hour exposure 

to 150 ppm of [14C]-1,2-dichloroethane. The exact metabolic pathways were not determined, but an 

observed depression of hepatic nonprotein sulfhydryl groups may indicate that glutathione plays a major 

role in the metabolism of 1,2-dichloroethane following inhalation exposure. Saturation of 

biotransformation enzymes was not apparent at this dose since 84% of the administered 14C was recovered 

as urinary metabolites and only 2% of the administered 14C was recovered as parent compound in the 

expired air. However, the data of Spreafico et al. (1980) suggest that saturation does occur after 

inhalation exposure in rats, since peak blood levels of 1,2-dichloroethane rose 22-fold when the exposure 

concentration was increased from 50 to 250 ppm. Based on the data of these 2 groups of investigators, it 

appears that saturation of 1,2-dichloroethane metabolism occurs when blood levels reach 5–10 μg/mL 

blood or after exposure to 150–250 ppm 1,2-dichloroethane. When blood concentrations of 1,2-dichloroethane exceed these levels (i.e., at exposure concentrations $150 ppm), manifestations of toxicity became 

more apparent. For example, Maltoni et al. (1980) reported that most of the toxicity associated with 

inhalation exposure to 250 ppm 1,2-dichloroethane in rats and mice was alleviated when exposure levels 

were reduced to 150 ppm, and no treatment-related effects were noted at 50 ppm. These findings suggest 

that 1,2-dichloroethane-induced toxicity occurs once a threshold blood level has been exceeded. 

3.4.3.2 Oral Exposure 

Reitz et al. (1982) also studied the metabolism of 1,2-dichloroethane following the administration of 

single oral doses of 150 mg/kg [14C]-1,2-dichloroethane. Again, the exact metabolic pathways were not 

determined, but the observation that hepatic nonprotein sulfhydryl groups were depressed indicated that 

glutathione may also play a major role in the metabolism of 1,2-dichloroethane following oral exposure. 

Saturation of biotransformation enzymes was apparent at this dose since only 60% of the administered 

radiolabel was recovered as urinary metabolites, and 29% of the administered radiolabel was associated 

with unchanged parent compound in the expired air. As with inhalation, it appeared that saturation of 

1,2-dichloroethane metabolism occurred when blood levels reached 5–10 μg/mL blood or after 

administration of $25 mg/kg 1,2-dichloroethane (D'Souza et al.1988; Reitz et al. 1982; Spreafico et al. 

1980). This blood threshold level again correlated with observed toxicity in animal studies (NCI 1978), 

as discussed above. 
 

1,2-DICHLOROETHANE 104 

3. HEALTH EFFECTS 

Although the saturable pathways appear to be the same for both oral and inhalation exposure, oral 

administration of 1,2-dichloroethane by gavage results in saturation at lower administered doses than 

inhalation exposure. Reitz et al. (1982) demonstrated that administration of 150 mg/kg 1,2-dichloroethane by gavage resulted in a 1.3-fold higher absolute dose to the animals than 150 ppm via inhalation 

(which is approximately equal to 502 mg/kg). Gavage administration produced approximately twice as 

much total metabolite as inhalation, and peak levels of 1,2-dichloroethane in blood were almost five times 

higher following gavage versus inhalation. Gavage administration may not represent typical oral 

exposure in humans. Gavage administration results in large bolus doses absorbed at one time thereby 

leading to spikes in blood levels and a more pronounced expression of toxicity. Oral exposure to 

1,2-dichloroethane by humans will most likely occur via ingestion of contaminated drinking water in 

small doses spread out over the course of a day. In such instances, biotransformation processes will 

probably not become saturated; thus, the risk for adverse effects is not as high as would be predicted from 

gavage administration of equivalent doses. 

3.4.3.3 Intraperitoneal Exposure 

In female albino mice given 1,2-dichloroethane intraperitoneally, the metabolism of 1,2-dichloroethane 

appeared to be initiated by hydrolytic dehalogenation followed by reduction to yield 2-chloroethanol 

(Yllner 1971b). This was then converted to 2-chloroacetic acid by microsomal oxidation. Final 

metabolites identified in the urine of these animals in percent radioactivity recovered included 

S-carboxymethyl-L-cysteine (44–46% free; 0.5–5% conjugated), thiodiacetic acid (33–34%), 

S,S'-ethylene-bis-cysteine (1.0%), which are indicative of glutathione conjugation, in addition to 

chloroacetic acid (6–23%) and 2-chloroethanol (0–0.8%) (see Figure 3-3). 

3.4.3.4 Other Routes of Exposure 

The pathways of 1,2-dichloroethane metabolism have been elucidated primarily by in vitro studies in 

isolated rat hepatic microsomes. 

In one in vitro study, 1,2-dichloroethane was metabolized mainly to chloroacetaldehyde by hepatic 

nuclear cytochrome P-450 (Casciola and Ivanetich 1984). Guengerich et al. (1980) proposed a pathway 

involving microsomal cytochrome P-450 (in the presence of oxygen and nicotinamide adenine 

dinucleotide phosphate [reduced form] [NADPH]) and MFO to explain the production of 

chloroacetaldehyde. 1,2-Dichloroethane undergoes oxygen insertion to yield an unstable chlorohydrin, 
1,2-DICHLOROETHANE 105 

3. HEALTH EFFECTS 

which spontaneously dechlorinates to form 2-chloroacetaldehyde that can react with macromolecules. 

2-Chloroacetaldehyde can also be reduced to chloroethanol or be further oxidized to chloroacetic acid. 

Guengerich et al. (1991) demonstrated that cytochrome P-450 2E1 is the primary oxidation catalyst of 

1,2-dichloroethane in humans. 

Conjugation of 1,2-dichloroethane with glutathione is proposed to be a major metabolic pathway in vivo 

(Yllner 1971b); this has been confirmed by the in vitro studies of Livesey and Anders (1979), Anders and 

Livesey (1980), and Jean and Reed (1989). This pathway is outlined on the right side of Figure 3-3. The 

depletion of hepatic glutathione by 1,2-dichloroethane has been demonstrated in vitro (Albano et al. 

1984). Johnson (1967) demonstrated that, in vitro, conjugation of 2-chloroacetic acid with glutathione 

also proceeded by a nonenzymatic process, yielding S-carboxymethylglutathione. This compound 

subsequently degraded to yield glycine, glutamic acid, and S-carboxymethylcysteine. S-carboxymethylcysteine may then be further oxidized to thiodiglycolic acid. Both S-carboxymethylcysteine and 

thiodiglycolic acid were found as urinary metabolites in rats and mice given 1,2-dichloroethane in vivo 

(Spreafico et al. 1980; Yllner 1971b). This scheme is also supported by studies with 1,2-dibromoethane 

(Nachtomi et al. 1966; Van Bladeren 1983). 

3.4.4 Elimination and Excretion 

3.4.4.1 Inhalation Exposure 

Women inhaling approximately 15.6 ppm 1,2-dichloroethane present in the workplace air eliminated the 

compound unchanged in the expired air. Similar observations were also reported in women exposed via 

dermal contact to liquid 1,2-dichloroethane. In both cases, the amount of 1,2-dichloroethane in the 

expired air was greater immediately following exposure and decreased gradually with time (Urusova 

1953). 

Elimination of 1,2-dichloroethane following inhalation exposure in rats occurred primarily via the 

excretion of soluble metabolites and unchanged parent compound in the urine and carbon dioxide in the 

expired air (Reitz et al. 1982; Spreafico et al. 1980). Urinary metabolites accounted for 84% of the 

absorbed dose, unchanged fecal 1,2-dichloroethane accounted for 2%, and carbon dioxide accounted for 

7% of the absorbed dose following the inhalation of 150 ppm by rats (Reitz et al. 1982). The primary 

urinary metabolites identified in rats following inhalation exposure were thiodiacetic acid (70%) and 

thiodiacetic acid sulfoxide (26–28%). The rapidity of elimination is demonstrated by the fact that a few 
1,2-DICHLOROETHANE 106 

3. HEALTH EFFECTS 

hours after exposure, 1,2-dichloroethane was not detected in blood and was detected only to a small 

extent 48 hours after exposure in various tissues (liver, kidney, lung, spleen, forestomach, stomach, 

carcass) (Reitz et al. 1982). 

Spreafico et al. (1980) studied the kinetics of 1,2-dichloroethane excretion in rats following inhalation 

exposure of 50 or 250 ppm 1,2-dichloroethane for 5 hours. They determined that elimination was 

monophasic with the half-times of 12.7 and 22 minutes at 50 and 250 ppm exposure, respectively. The 

disappearance of 1,2-dichloroethane was dose-dependent since the percentage of parent compound 

recovered in the expired air increased exponentially with dose. This was presumably a reflection of the 

saturable metabolic processes. Spreafico et al. (1980) also determined that elimination of 1,2-dichloroethane from adipose tissue was slower than elimination of 1,2-dichloroethane from the blood, liver, and 

lung. 

3.4.4.2 Oral Exposure 

No studies were located regarding excretion in humans after oral exposure to 1,2-dichloroethane. 

Elimination of 1,2-dichloroethane following oral administration in rats was also rapid and occurred 

primarily via excretion of soluble metabolites in the urine, and unchanged parent compound and carbon 

dioxide in the expired air (Mitoma et al. 1985; Payan et al. 1993; Reitz et al. 1982; Spreafico et al. 1980). 

Reitz et al. (1982) conducted a complete 14C-balance study in male Osborne-Mendel rats and found that 

urinary metabolites accounted for 60% of the radioactivity administered as a single oral dose of 150 mg 

14C-1,2-dichloroethane/kg body weight. Unchanged 1,2-dichloroethane in the breath accounted for 29% 

and carbon dioxide in the breath accounted for 5% of the administered radioactivity. The remaining 6% 

of the administered radioactivity was recovered in the carcass, feces, and cage washes. The primary 

urinary metabolites identified were the same as those seen following inhalation exposure—thiodiacetic 

acid (70%) and thiodiacetic acid sulfoxide (26–28%). Elimination of 1,2-dichloroethane was 96% 

complete within 48 hours. The results were similar in rats given a single gavage dose of 150 mg/kg 

following 2 years of intermittent inhalation exposure to 50 ppm of 1,2-dichloroethane (Cheever et al. 

1990). 

Mitoma et al. (1985) studied the elimination of single gavage doses of 14C-labeled 1,2-dichloroethane 

from rats and mice (doses of 100 and 150 mg/kg, respectively, in corn oil) after pretreatment with 

unlabeled compound 5 days per week for 4 weeks. At 48 hours after administration of the radiolabeled 
1,2-DICHLOROETHANE 107 

3. HEALTH EFFECTS 

compound, expired volatile metabolites, CO2, excreta (feces and urine), and the carcass accounted for 

approximately 11.5, 8.2, 69.5, and 7% of administered radioactivity in rats, and 7.7, 18.2, 81.9, and 2.4% 

of the administered dose in mice. 

Spreafico et al. (1980) studied the kinetics of 1,2-dichloroethane excretion in rats following the oral 

administration of 50 mg/kg 1,2-dichloroethane (in corn oil), and found that kinetics were best described 

by a two-compartment model. Withey et al. (1983) reported that administration in water resulted in a 

shorter elimination half-time than administration in vegetable oil. Reitz et al. (1982) also reported a 

two-compartment model of elimination following the gavage administration of 150 mg/kg 1,2-dichloroethane. The initial elimination phase had a half-time of .90 minutes, but elimination became more rapid 

when blood levels fell to 5–10 μg/mL, characterized by a half-life of approximately 20–30 minutes. This 

is in contrast, however, to what was observed following inhalation exposure. Spreafico et al. (1980) 

suggested that the oral profile represented both an absorption-distribution phase and an elimination phase, 

whereas the inhalation profile reflected only elimination. This elimination of 1,2-dichloroethane was also 

dose-dependent following oral administration in rats, as the percentage of parent compound recovered in 

the expired air increased exponentially with dose. Again, this is a reflection of saturable metabolic 

processes. The rate of elimination from adipose tissue was similar to that from blood and other tissues, in 

contrast to the results for inhalation exposure. 

These results indicate that 1,2-dichloroethane will most likely not accumulate in nonlipid components of 

the human body following repeated exposure by any route, as elimination of the compound is rapid and 

complete. Available data also suggest that 1,2-dichloroethane is not particularly persistent in adipose 

tissue following oral exposure (Spreafico et al. 1980), but it may accumulate to some extent in adipose 

tissue after inhalation exposure (Spreafico et al. 1980) and/or in breast milk of nursing women (Urusova 

1953). 

3.4.4.3 Dermal Exposure 

1,2-Dichloroethane was eliminated unchanged in the expired air following dermal exposure of nursing 

mothers to liquid 1,2-dichloroethane in the workplace (Urusova 1953). The amount of 1,2-dichloroethane 

in the expired air was greatest immediately after skin contact and gradually decreased with time. 

No studies were located regarding excretion in animals after dermal exposure to 1,2-dichloroethane. 
1,2-DICHLOROETHANE 108 

3. HEALTH EFFECTS 

3.4.4.4 Other Routes of Exposure 

Studies conducted in animals in which 1,2-dichloroethane was administered via other routes (e.g., 

intraperitoneal or intravenous) support the findings of the studies discussed above; excretion of 

1,2-dichloroethane via urine and expired air was rapid and complete, and the route of excretion as well as 

the form of the chemical excreted were dose-dependent (Spreafico et al. 1980; Yllner 1971b). 

Estimates of an elimination constant (ke) for 1,2-dichloroethane were similar between two- and threecompartment pharmacokinetic models fitted to a time-series of blood concentration data that were 

obtained from rats given single intravenous doses (Withey and Collins 1980). The ke values for 

elimination from blood were roughly inversely related to dose; mean values of 0.143, 0.122, 0.091, 0.096, 

or 0.097 were obtained at dose levels of 3, 6, 9, 12, or 15 mg/kg, respectively. 

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

Physiologically based pharmacokinetic (PBPK) models use mathematical descriptions of the uptake and 

disposition of chemical substances to quantitatively describe the relationships among critical biological 

processes (Krishnan et al. 1994). PBPK models are also called biologically based tissue dosimetry 

models. PBPK models are increasingly used in risk assessments, primarily to predict the concentration of 

potentially toxic moieties of a chemical that will be delivered to any given target tissue following various 

combinations of route, dose level, and test species (Clewell and Andersen 1985). Physiologically based 

pharmacodynamic (PBPD) models use mathematical descriptions of the dose-response function to 

quantitatively describe the relationship between target tissue dose and toxic end points. 

PBPK/PD models refine our understanding of complex quantitative dose behaviors by helping to 

delineate and characterize the relationships between: (1) the external/exposure concentration and target 

tissue dose of the toxic moiety, and (2) the target tissue dose and observed responses (Andersen et al. 

1987; Andersen and Krishnan 1994). These models are biologically and mechanistically based and can 

be used to extrapolate the pharmacokinetic behavior of chemical substances from high to low dose, from 

route to route, between species, and between subpopulations within a species. The biological basis of 

PBPK models results in more meaningful extrapolations than those generated with the more conventional 

use of uncertainty factors. 
1,2-DICHLOROETHANE 109 

3. HEALTH EFFECTS 

The PBPK model for a chemical substance is developed in four interconnected steps: (1) model 

representation, (2) model parametrization, (3) model simulation, and (4) model validation (Krishnan and 

Andersen 1994). In the early 1990s, validated PBPK models were developed for a number of 

toxicologically important chemical substances, both volatile and nonvolatile (Krishnan and Andersen 

1994; Leung 1993). PBPK models for a particular substance require estimates of the chemical substancespecific physicochemical parameters, and species-specific physiological and biological parameters. The 

numerical estimates of these model parameters are incorporated within a set of differential and algebraic 

equations that describe the pharmacokinetic processes. Solving these differential and algebraic equations 

provides the predictions of tissue dose. Computers then provide process simulations based on these 

solutions. 

The structure and mathematical expressions used in PBPK models significantly simplify the true 

complexities of biological systems. If the uptake and disposition of the chemical substance(s) is 

adequately described, however, this simplification is desirable because data are often unavailable for 

many biological processes. A simplified scheme reduces the magnitude of cumulative uncertainty. The 

adequacy of the model is, therefore, of great importance, and model validation is essential to the use of 

PBPK models in risk assessment. 

PBPK models improve the pharmacokinetic extrapolations used in risk assessments that identify the 

maximal (i.e., the safe) levels for human exposure to chemical substances (Andersen and Krishnan 1994). 

PBPK models provide a scientifically sound means to predict the target tissue dose of chemicals in 

humans who are exposed to environmental levels (for example, levels that might occur at hazardous waste 

sites) based on the results of studies where doses were higher or were administered in different species. 

Figure 3-4 shows a conceptualized representation of a PBPK model. 

A PBPK model has been developed that quantitates the amount of 1,2-dichloroethane and its metabolites 

that reach the blood and target tissues following different exposure routes (D'Souza et al. 1987, 1988). As 

discussed in Section 3.4.3, 1,2-dichloroethane is metabolized by a saturable oxidation pathway and direct 

conjugation with glutathione. The model predicts that inhalation exposures to 1,2-dichloroethane produce 

less glutathione-conjugate metabolites in the liver and lung of rats than equivalent oral exposures. This 

prediction offers a possible explanation for why 1,2-dichloroethane is carcinogenic in rats by the oral 

route (NCI 1978), but not following inhalation exposures (Maltoni et al. 1980). This may have important 

implications for extrapolating cancer risk from high doses (above MFO saturation) to environmental 

exposures (below MFO saturation). The PBPK model may also be useful for extrapolating toxicity data 
3. HEALTH EFFECTS 

Figure 3-4. Conceptual Representation of a Physiologically Based
 

Pharmacokinetic (PBPK) Model for a 

Hypothetical Chemical Substance
 

Inhaled chemical Exhaled chemical 

Ingestion 

Skin 

Kidney 

Richly 

perfused 

tissues 

Slowly 

perfused 

tissues 

Fat 

Liver 

Lungs 

V 

E 

N 

O 

U 

S 

B 

L 

O 

O 

D 

GI 

Tract 

Vmax Km 

Urine 

Chemicals in air 

contacting skin 

Feces 

A
 

R
 

T
 

E
 

R
 

I
 

A
 

L
 

B 

L 

O 

O 

D 

1,2-DICHLOROETHANE 110 

Source: adapted from Krishnan et al. 1994 

Note: This is a conceptual representation of a physiologically based pharmacokinetic 

(PBPK) model for a hypothetical chemical substance. The chemical substance is 

shown to be absorbed via the skin, by inhalation, or by ingestion, metabolized in the 

liver, and excreted in the urine or by exhalation. 
1,2-DICHLOROETHANE 111 

3. HEALTH EFFECTS 

from animals to humans because the level of glutathione in the liver appears to modulate the toxic effects 

of 1,2-dichloroethane (see discussion in Section 3.5). However, this model needs to be tested and 

validated. 

3.5 MECHANISMS OF ACTION 

3.5.1 Pharmacokinetic Mechanisms 

The physical properties of 1,2-dichloroethane, particularly its lipophilic nature, high vapor pressure, and 

high serum/air partition coefficient, suggest that it is likely to be absorbed across the alveolar membranes 

of the lung, mucosal membranes of the gastrointestinal tract, and the skin by passive diffusion. Once in 

the body, it is widely distributed, with the greatest amounts accumulating in the more lipophilic tissues; 

this probably also occurs by passive diffusion. 

There is compelling evidence that the toxicity and carcinogenicity of 1,2-dichloroethane are associated 

with its metabolism to active intermediates. Studies in rats and mice indicate that 1,2-dichloroethane is 

metabolized to 2-chloroacetaldehyde, S-(2-chloroethyl)glutathione, and other putative reactive 

intermediates capable of binding covalently to cellular macromolecules (Fabricant and Chalmers 1980; 

Jean and Reed 1989). The ability of a chemical to bind covalently to cellular macromolecules is often 

correlated with the induction of toxic and carcinogenic effects. In addition, 1,2-dichloroethane has been 

shown to promote lipid peroxidation in vitro (Sano and Tappel 1990; Tse et al. 1990). Lipid peroxidation 

is also associated with tissue damage. The lag time between inhalation exposure and onset of effects 

reported by Nouchi et al. (1984) in an occupationally exposed 51-year-old male may have been a 

reflection, in part, of the time required to metabolize 1,2-dichloroethane to active intermediates. 

The level of glutathione present in the liver appears to modulate effects of 1,2-dichloroethane in animals. 

Glutathione is believed to be heavily involved in the biotransformation of 1,2-dichloroethane (Anders and 

Livesey 1980; Yllner 1971b). The metabolic pathway of 1,2-dichloroethane is linear at low doses, but at 

higher concentrations, as the P-450 enzymes become saturated, the amount of glutathione conjugate 

produced rises disproportionately with increasing administered dose; at very high doses, the GSH 

pathway is also saturated, and the glutathione conjugate produced declines disproportionately with 

increasing dose (D'Souza et al. 1987). It has been suggested that 1,2-dichloroethane-induced toxicity 

occurs when the biotransformation processes are saturated, thereby allowing higher levels of 
1,2-DICHLOROETHANE 112 

3. HEALTH EFFECTS 

1,2-dichloroethane to circulate throughout the body and conjugate with glutathione instead of being 

detoxified and eliminated (D'Souza et al. 1987; Reitz et al. 1982). 

This might explain the observation that large drinking water doses fail to produce the same toxic effects 

as smaller gavage doses (Munson et al. 1982). Gavage administration involves the placement of large 

bolus doses in the stomach that are absorbed at one time, thereby leading to spikes in blood levels and the 

subsequent expression of toxicity. However, drinking water exposure results in ingestion of contaminated 

water in small doses spread out over the course of a day. In such instances, biotransformation processes 

are not as likely to become saturated, and the risk of adverse effects is not as high as would be predicted 

from gavage administration of equivalent doses. The time required for saturation of biotransformation 

processes to occur might have contributed to the lag time, observed by Nouchi et al. (1984), between 

exposure and onset of toxic effects in an exposed human male, since the exposure dose (unknown) was 

undoubtedly high. 

3.5.2 Mechanisms of Toxicity 

Specific mechanisms for 1,2-dichloroethane-induced toxicity have not been elucidated. Studies in rats 

and mice indicate that 1,2-dichloroethane may be metabolized to 2-chloroacetaldehyde, 

S-(2-chloroethyl)glutathione, and other putative reactive intermediates capable of binding covalently to 

cellular macromolecules in the liver, kidney, and other tissues (Fabricant and Chalmers 1980; Jean and 

Reed 1989; Lock 1989). 1,2-Dichloroethane promoted lipid peroxidation in rat liver cells (Sano and 

Tappel 1990) and arterial endothelial and aortic smooth muscle cells (Tse et al. 1990) in vitro, suggesting 

another possible mechanism by which this chemical might produce toxic effects. 

Available evidence suggests that toxicity of 1,2-dichloroethane in various tissues is largely mediated by 

reactive intermediates formed by conjugation with glutathione (Lock 1989). High levels of glutathioneS-transferases, the family of enzymes that catalyze the conjugation of xenobiotics with glutathione, are 

present in liver, kidney, intestine, testis, adrenal, and lung, primarily (>95%) in the cytoplasm (Parkinson 

1996). Putative glutathione-dependent metabolites, such as S-(2-chloroethyl)glutathione and 

S-(2-chloroethyl)-L-cysteine, are thought to spontaneously rearrange to form electrophilic episulfonium 

ions that can bind to cellular macromolecules (Peterson et al. 1988). Rapid depletion of hepatocellular 

glutathione and binding of S-(2-chloroethyl)glutathione and S-(2-chloroethyl)-L-cysteine to liver DNA 

and protein have been demonstrated in vitro (Jean and Reed 1989). Similarly, the renal cortex contains 

substantial amounts and high activity of glutathione S-transferases that perform the initial conjugation 
1,2-DICHLOROETHANE 113 

3. HEALTH EFFECTS 

reaction (Lock 1989), and the conjugates S-(2-chloroethyl)glutathione and S-(2-chloroethyl)-L-cysteine 

have been identified as nephrotoxic in rats. Cytochrome P-450, which catalyzes competing metabolic 

reactions, has relatively low activity in the kidney, thus shifting the metabolism of 1,2-dichloroethane in 

the kidney toward production of toxic metabolites. 

Differences in carcinogenic response have been observed between the positive oral gavage study (NCI 

1978) and the negative inhalation study (Maltoni et al. 1980) summarized in Sections 3.2.1.7 and 3.2.2.7. 

These inconsistent cancer findings could be attributed to a number of factors, including different strains 

of rats and inhalation study limitations, including intermittent exposures, an MTD that was exceeded at 

the highest dose tested, and poor survival rates. The route-related difference in carcinogenic response 

may also be explained on the basis of metabolic differences and the saturation of the detoxification/ 

excretion mechanism occurring between the gavage dose and the longer-term inhalation dose, as proposed 

by Reitz et al. (1982) and discussed in Section 3.5.1. At lower doses, metabolic saturation appeared to 

occur sooner after oral administration than after inhalation exposure. Reitz et al. (1982) also suggested 

that the expression of 1,2-dichloroethane-induced toxicity occurred when the biotransformation processes 

were saturated, thereby allowing higher levels of 1,2-dichloroethane to circulate throughout the body 

instead of being detoxified and eliminated. The 1,2-dichloroethane inhalation study therefore may not 

have produced peak blood levels high enough to saturate the detoxification mechanisms and produce a 

detectable incidence of tumors. Route-related differences in immunologic and several other toxic 

responses have similarly been observed, which may also be due to the saturation of the detoxification/ 

excretion mechanism as a result of the bolus gavage dosing. 

3.5.3 Animal-to-Human Extrapolations 

The metabolism of 1,2-dichloroethane has not been studied in humans. The lack of this information 

precludes a nonspeculative attempt to discuss potential interspecies differences or similarities in the 

toxicity of 1,2-dichloroethane, as well as a determination of which animal species is the most appropriate 

model for humans. Extrapolations of 1,2-dichloroethane oral toxicity data from animals to humans 

should consider the type of exposure because, as discussed in Section 3.5.1, some of the differences in 

toxic and carcinogenic responses in animal studies can be explained on the basis of saturation of the 

detoxification/excretion mechanism due to bolus (gavage) administration. 
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3.6 ENDOCRINE DISRUPTION 

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, or otherwise 

interfere with the normal function of the endocrine system. Chemicals with this type of activity are most 

commonly referred to as endocrine disruptors. Some scientists believe that chemicals with the ability to 

disrupt the endocrine system are a potential threat to the health of humans, aquatic animals, and wildlife. 

Others believe that endocrine disrupting chemicals do not pose a significant health risk, particularly in 

light 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 

compounds are derived from plants and are similar in structure and action as endogenous estrogen. While 

there is some controversy over the public health significance of endocrine disrupting chemicals, it is 

agreed that the potential exists for these compounds to affect the synthesis, secretion, transport, binding, 

action, or elimination of natural hormones in the body that are responsible for the maintenance of 

homeostasis, reproduction, development, and/or behavior (EPA 1997). As a result, endocrine disruptors 

may play a role in the disruption of sexual function, immune suppression, and neurobehavioral function. 

Endocrine disruption is also thought to be involved in the induction of breast, testicular, and prostate 

cancers, as well as endometriosis (Berger 1994; Giwercman et al. 1993; Hoel et al. 1992). 

No studies regarding endocrine disruption in humans and animals after exposure to 1,2-dichloroethane 

were located. 

No in vitro studies regarding endocrine disruption of 1,2-dichloroethane were located. 

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. 
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Children are not small adults. They differ from adults in their exposures and may differ in their 

susceptibility to hazardous chemicals. Children’s unique physiology and behavior can influence the 

extent of their exposure. Exposures of children are discussed in Section 6.6 Exposures of Children. 

Children sometimes differ from adults in their susceptibility to hazardous chemicals, but whether there is 

a difference depends on the chemical (Guzelian et al. 1992; NRC 1993). Children may be more or less 

susceptible than adults to health effects, and the relationship may change with developmental age 

(Guzelian et al. 1992; NRC 1993). Vulnerability often depends on developmental stage. There are 

critical periods of structural and functional development during both prenatal and postnatal life and a 

particular structure or function will be most sensitive to disruption during its critical period(s). Damage 

may not be evident until a later stage of development. There are often differences in pharmacokinetics 

and metabolism between children and adults. For example, absorption may be different in neonates 

because of the immaturity of their gastrointestinal tract and their larger skin surface area in proportion to 

body weight (Morselli et al. 1980; NRC 1993); the gastrointestinal absorption of lead is greatest in infants 

and young children (Ziegler et al. 1978). Distribution of xenobiotics may be different; for example, 

infants have a larger proportion of their bodies as extracellular water and their brains and livers are 

proportionately larger (Altman and Dittmer 1974; Fomon 1966; Fomon et al. 1982; Owen and Brozek 

1966; Widdowson and Dickerson 1964). The infant also has an immature blood-brain barrier (Adinolfi 

1985; Johanson 1980) and probably an immature blood-testis barrier (Setchell and Waites 1975). Many 

xenobiotic metabolizing enzymes have distinctive developmental patterns. At various stages of growth 

and development, levels of particular enzymes may be higher or lower than those of adults, and 

sometimes unique enzymes may exist at particular developmental stages (Komori et al. 1990; Leeder and 

Kearns 1997; NRC 1993; Vieira et al. 1996). Whether differences in xenobiotic metabolism make the 

child more or less susceptible also depends on whether the relevant enzymes are involved in activation of 

the parent compound to its toxic form or in detoxification. There may also be differences in excretion, 

particularly in newborns who all have a low glomerular filtration rate and have not developed efficient 

tubular secretion and resorption capacities (Altman and Dittmer 1974; NRC 1993; West et al. 1948). 

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 while 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 
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alveoli being less developed, which results in a disproportionately smaller surface area for alveolar 

absorption (NRC 1993). 

Data on the health effects of 1,2-dichloroethane exposure in children are limited to a single case report of 

a 14-year-old boy who swallowed 15 mL of the compound (Yodaiken and Babcock 1973). The most 

immediate signs of toxicity were headache and staggering gait within 2 hours of exposure, followed soon 

after by lethargy and vomiting. During the next few days, the boy developed symptoms of toxicity, 

increasing in variety and severity, that involved several organ systems, including adverse hematological 

effects, pulmonary edema, cardiac arrest (he was resuscitated), and eventual death on the 5th day after 

exposure from massive hepatic necrosis and renal tubular necrosis. Data from this case report and from 

reports of adult humans who died following acute exposure to high levels by inhalation or ingestion are 

consistent with animal studies indicating that the main targets of acute toxicity include the central nervous 

system, respiratory tract, stomach, liver, and kidneys. Considering the consistency of effects in acutely 

exposed humans and animals, and data showing that the liver, kidney, and immune system are sensitive 

targets of lower-dose and longer-term inhalation and oral exposures in animals, it is reasonable to assume 

that effects in these tissues would also be seen in similarly exposed adults and children. 

No studies that provide reliable information on adverse developmental effects in humans exposed to 

1,2-dichloroethane are available. A cross-sectional epidemiologic study that investigated whether 

elevated levels of routinely sampled organic contaminants in New Jersey public water systems, including 

1,2-dichloroethane, were associated with increased prevalences of adverse birth outcomes (Bove 1996; 

Bove et al. 1995) was located. A number of associations between various chemicals and birth outcomes 

were found, including a positive association between ingestion of 1,2-dichloroethane in drinking water 

and major cardiac birth defects; however, the mixed chemical exposures indicate that the results are only 

suggestive, do not establish a cause-and-effect relationship, and should be interpreted with caution. 

Studies in rats, mice, and rabbits indicate that 1,2-dichloroethane is not developmentally toxic following 

inhalation or oral gestational exposure, although indications of embryolethality at maternally toxic doses 

have been reported (Kavlock et al. 1979; Lane et al. 1982; Payan et al. 1995; Rao et al. 1980). 

Evidence from mouse studies suggests that the specific nature of oral exposure may play a role in the 

degree of immunotoxicity expressed in young animals. Bolus doses of 1,2-dichloroethane appear to be 

more effective in eliciting an immunotoxic response than drinking-water exposures in 5-week-old mice. 

There was a significant, dose-related reduction in IgM response to sheep erythrocytes, and a significant, 
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3. HEALTH EFFECTS 

but not dose-related, reduction in delayed-type hypersensitivity response to sheep erythrocytes in 

5-week-old CD-1 mice exposed for 14 days by gavage to 4.9 and 49 mg/kg/day (Munson et al. 1982). In 

mice provided 49 mg/kg/day, these effects were accompanied by a 30% decrease in total leukocyte 

number. In contrast, mice given drinking water containing 189 mg/kg/day of 1,2-dichloroethane for 

90 days beginning at 5 weeks of age displayed no treatment-related effects on either the antibody-forming 

cell response or the delayed-type hypersensitivity response after immunization with sheep erythrocyte 

antigens (Munson et al. 1982). The fact that the animal evidence for oral immunotoxicity of 

1,2-dichloroethane includes decreased immune responses in 5-week-old mice provides a limited 

indication of the potential susceptibility of children to immunotoxic effects, particularly after bolus 

ingestion by children, that could occur, for example, with accidental ingestion of older household 

products that contain 1,2-dichloroethane. 

Young mice were also susceptible to reduced immune function after brief inhalation exposure to 

1,2-dichloroethane. A single 3-hour exposure to 5–11 ppm of 1,2-dichloroethane induced increased 

susceptibility to S. zooepidemicus (i.e., increased mortality following infection) in 4- to 5-week-old 

female mice, suggesting reduced pulmonary immunological defenses in the exposed mice (Sherwood et 

al. 1987). No immunological effects were observed at 2.3 ppm. Young female mice exposed to 11 ppm 

also had reduced bactericidal activity in the lungs 3 hours after inhalation challenge with K. pneumoniae. 

In contrast, young male rats (ages ranging from 4 to 5 weeks) that were exposed once to 200 ppm for 

5 hours or 100 ppm 5 hours/day for 12 days did not exhibit any increased susceptibility to infection from 

these microbes, suggesting that rats may be less susceptible to the detrimental immunological effects of 

1,2-dichloroethane than mice and/or that male rodents are less susceptible than females (Sherwood et al. 

1987). The relevance of the young mouse inhalation data to child susceptibility is unknown, particularly 

in the light of the observed interspecies differences. However, the data do suggest that it would be 

prudent to prevent 1,2-dichloroethane inhalation exposures in children such as those that might occur 

during, and for several days after, using old wallpaper or carpet adhesives that contain 1,2-dichloroethane. 

No studies that evaluated for the distribution of 1,2-dichloroethane or its metabolites across the placenta 

in humans were located. However, there is some evidence that 1,2-dichloroethane and/or its metabolites 

crosses the placenta after inhalation and oral exposures in animals. 1,2-Dichloroethane was found in 

maternal blood (83.6±20.2 mg %), placental tissue (43.0±9.6 mg %), amniotic fluid (55.5±11.1 mg %), 

and fetal tissue (50.6±11.5 mg %) after inhalation exposure of female rats to 247±10 ppm 1,2-dichloroethane during pregnancy (Vozovaya 1977). Additional evidence of transplacental distribution of 

1,2-dichloroethane after inhalation exposure is provided by Withey and Karpinski (1985), who found that 
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3. HEALTH EFFECTS 

the geometric mean concentration of 1,2-dichloroethane in the fetuses of rats that inhaled 150–2,000 ppm 

for 5 hours increased linearly with increasing exposure level. However, the reliability of the Vozovaya 

data is unclear, and the methods for evaluating 1,2-dichloroethane tissue concentrations were not reported 

in Withey and Karpinski (1985). 

There is clearer evidence for transplacental distribution of 1,2-dichloroethane and/or its metabolites after 

maternal oral exposure. Payan et al. (1995) evaluated [14C]-1,2-dichloroethane distribution in maternal 

rats following a single oral bolus dose of approximately 160 mg/kg on gestation day 12 or 18. In both 

cases, transplacental distribution of radiocarbon was demonstrated by the presence of radioactivity in the 

developing conceptus. A greater accumulation occurred in the developing fetus and placenta 48 hours 

after the gestation-day 18 administration than after the gestation-day 12 administration. At 48 hours after 

the gestation-day 18 dosing, the majority of residual radioactivity burden was located in the fetus 

(0.167% of administered dose) and the liver (0.156% of administered dose). 

No studies regarding 1,2-dichloroethane metabolism in children were located. The metabolism of 

1,2-dichloroethane is well described (see Figure 3-3), and it is reasonable to assume that the metabolic 

pathways are, for the most part, the same between adults and children. However, the expression of 

certain enzymes is known to be developmentally regulated, and one of these enzymes may be involved in 

1,2-dichloroethane metabolism. NAT is involved in 1,2-dichloroethane metabolism at a step subsequent 

to GSH conjugation (see Figure 3-3). NAT performs the N-acetylation of S-carboxymethyl-L-cysteine to 

N-acetyl-S-carboxymethyl-L-cysteine, a major urinary metabolite. There are, however, two NATs 

(NAT1 and NAT2) that are expressed in humans with separate but overlapping substrate specificities 

(Parkinson 1996). NAT2 is apparently expressed only in the liver and the gut (Parkinson 1996), and is 

known to be developmentally regulated (Leeder and Kearns 1997). Some NAT2 activity is present in the 

fetus at 16 weeks, but NAT2 activity is low in virtually 100% of infants, not reaching adult activity levels 

until 1 to 3 years of age (Leeder and Kearns 1997). It is not clear in NTP (1991a), the source of the 

metabolism information in Figure 3-3, whether the NAT involved in 1,2-dichloroethane metabolism is 

NAT1 or NAT2, although both enzymes N-acetylate some xenobiotics equally well (Parkinson 1996). 

1,2-Dichloroethane has been detected in human milk (EPA 1980a; Urusova 1953), indicating that 

developing children could possibly be exposed to 1,2-dichloroethane from breast-feeding mothers. The 

importance of this route of developmental exposure is unclear because current data on the concentration 

of 1,2-dichloroethane in breast milk are not available. 1,2-Dichloroethane also accumulated in the 

adipose tissue of rats after inhalation exposure and was eliminated from fat more slowly than from blood, 
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3. HEALTH EFFECTS 

liver, and lung (Spreafico et al. 1980), suggesting the possibility that the maternal body burden of 

1,2-dichloroethane in fat could be available for exposure to the fetus or nursing infant for a somewhat 

extended period after maternal exposure. Supporting data for relatively slow elimination of 1,2-dichloroethane from fat are provided in an intravenous exposure study in rats (Withey and Collins 1980). 

3.8 BIOMARKERS OF EXPOSURE AND EFFECT 

Biomarkers are broadly defined as indicators signaling events in biologic systems or samples. They have 

been classified as markers of exposure, markers of effect, and markers of susceptibility (NAS/NRC 1989). 

Due to a nascent understanding of the use and interpretation of biomarkers, implementation of biomarkers 

as tools of exposure in the general population is very limited. A biomarker of exposure is a xenobiotic 

substance or its metabolite(s) or the product of an interaction between a xenobiotic agent and some target 

molecule(s) or cell(s) that is measured within a compartment of an organism (NAS/NRC 1989). The 

preferred biomarkers of exposure are generally the substance itself or substance-specific metabolites in 

readily obtainable body fluid(s), or excreta. However, several factors can confound the use and 

interpretation of biomarkers of exposure. The body burden of a substance may be the result of exposures 

from more than one source. The substance being measured may be a metabolite of another xenobiotic 

substance (e.g., high urinary levels of phenol can result from exposure to several different aromatic 

compounds). Depending on the properties of the substance (e.g., biologic half-life) and environmental 

conditions (e.g., duration and route of exposure), the substance and all of its metabolites may have left the 

body by the time samples can be taken. It may be difficult to identify individuals exposed to hazardous 

substances that are commonly found in body tissues and fluids (e.g., essential mineral nutrients such as 

copper, zinc, and selenium). Biomarkers of exposure to 1,2-dichloroethane are discussed in Section 3.8.1. 

Biomarkers of effect are defined as any measurable biochemical, physiologic, or other alteration within an 

organism that, depending on magnitude, can be recognized as an established or potential health 

impairment or disease (NAS/NRC 1989). This definition encompasses biochemical or cellular signals of 

tissue dysfunction (e.g., increased liver enzyme activity or pathologic changes in female genital epithelial 

cells), as well as physiologic signs of dysfunction such as increased blood pressure or decreased lung 

capacity. Note that these markers are not often substance specific. They also may not be directly 

adverse, but can indicate potential health impairment (e.g., DNA adducts). Biomarkers of effects caused 

by 1,2-dichloroethane are discussed in Section 3.8.2. 
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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 1,2-Dichloroethane 

Levels of 1,2-dichloroethane in breath, blood, and urine may be used to indicate exposure to this 

chemical. However, these measurements would have to be made soon after exposure, since 1,2-dichloroethane is rapidly eliminated from the body (see Section 3.4.4). In addition, it is not possible to establish 

from such measurements the precise environmental levels of 1,2-dichloroethane to which these 

individuals were exposed. A number of studies have investigated the relationship between tissue and 

environmental levels of 1,2-dichloroethane. In general, small amounts of 1,2-dichloroethane detected in 

the breath and urine (trace–0.2 ppb and 50–140 ng/L, respectively) were associated with exposure to 

1,2-dichloroethane in air and water (Barkley et al. 1980; Conkle et al. 1975). In 2 studies conducted by 

Wallace et al. (1984, 1986), levels of 1,2-dichloroethane in breath samples from 350 residents of New 

Jersey were consistently below the detection limit; therefore, no conclusions could be drawn from these 

studies. 1,2-Dichloroethane was also detected in the breath (14.3 ppm) and breast milk (0.54–0.64 mg %) 

of nursing women working in factory premises containing 15.6 ppm 1,2-dichloroethane in air (Urusova 

1953). These data are insufficient to characterize the relationship between environmental exposure to 

1,2-dichloroethane and resultant tissue and fluid levels. 

Urinary excretion of thioethers is another potentially useful biomarker of exposure to 1,2-dichloroethane. 

Payan et al. (1993) showed that total excreted urinary thioethers increased linearly with increasing oral 

dose (for doses between 0.25 and 4.04 mmol/kg [11.9 mg/kg/d and 400 mg/kg/d, respectively]) in male 

Sprague-Dawley rats during a 24-hour postadministration period, at a rate of 0.028 mmol thiol group 

eliminated per millimole of 1,2-dichloroethane administered. This occurred in spite of the fact that the 

total percentage of orally administered radioactivity excreted in the urine decreased with increasing dose 

(possibly due to saturation of certain metabolic pathways leading to urinary metabolites). Thioethers are 

commonly produced by conjugation reactions involving glutathione and comprise the primary urinary 

metabolites of 1,2-dichloroethane (see Sections 3.4.3 and 3.4.4). Increased urinary excretion of thioethers 

following exposure to 1,2-dichloroethane has been demonstrated in rats (Igwe et al. 1988; Payan et al. 

1993), showing that this end point is sensitive to 1,2-dichloroethane exposure. As discussed above for the 
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parent compound, rapid excretion of 1,2-dichloroethane and metabolites (essentially complete after 

48 hours in animal studies) means that measurements would have to be made soon after exposure to be of 

any value. There is an additional problem with use of increased urinary thioether excretion as a 

biomarker for 1,2-dichloroethane exposure. Since many xenobiotics form conjugates with glutathione, 

exposure to any number of compounds may increase urinary excretion of total thioethers (Monster 1986). 

Therefore, its use as a biomarker of 1,2-dichloroethane exposure is limited unless exposure to other 

compounds can be ruled out. Payan et al. (1993), however, found that urinary thiodiglycolic acid 

(measured by gas chromatography), a thioether compound that is not extractable by alkaline hydrolysis, is 

a more sensitive marker of 1,2-dichloroethane exposure than total thioethers. 

Kim and Guengerich (1989) found that urinary mercapturic acid was linearly dose-related to 

intraperitoneally injected 1,2-dibromoethane in rats, and the urinary excretion of mercapturic acid was 

correlated with formation of hepatic and renal DNA adducts. It is possible that a similar relationship 

exists for relevant 1,2-dichloroethane exposures, although the methods proposed by Kim and Guengerich 

(1989) would not discriminate between the halogens. 

Erve et al. (1996) investigated whether human hemoglobin, alkylated with the episulfonium ion of 

S-(2-chloroethyl)glutathione (a 1,2-dichloroethane metabolite via the glutathione-conjugation metabolic 

pathway), could be a useful biomarker for human exposure to 1,2-dichloroethane. They found that the 

method was not a very sensitive indicator for exposure, since an approximately 100-fold molar excess of 

S-(2-chloroethyl)glutathione over the hemoglobin concentration was required before alkylation was 

detectable in vitro. 

3.8.2 Biomarkers Used to Characterize Effects Caused by 1,2-Dichloroethane 

The health effects observed in humans exposed to 1,2-dichloroethane are all nonspecific effects and may 

be produced from any number of causes, including other causes that do not involve environmental 

exposure to xenobiotics such as 1,2-dichloroethane. Therefore, these effects would not be useful as 

indicators of exposure to 1,2-dichloroethane. Even if other causes could be ruled out, the specific levels 

that produce the various effects in humans are not known, so it would not be possible to quantify 

exposure based on the observed effects. 

The primary targets of 1,2-dichloroethane identified in humans are probably the central nervous system, 

liver, and kidney (for a detailed description of the health effects of 1,2-dichloroethane, see Section 3.2). 
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3. HEALTH EFFECTS 

Another likely target is the immune system, for which very limited information was available in humans 

but was the most sensitive target of 1,2-dichloroethane in animals. The effect on the immune system is 

immunosuppression. The observed biomarkers for this effect are reduced ability to fight induced 

bacterial infection, reduced immunoglobulin response to sheep erythrocytes, and reduced delayed-type 

hypersensitivity response to sheep erythrocytes, all of which show reduced immune system response to a 

challenge. The neurological effects observed included a variety of symptoms such as headache, 

irritability, drowsiness, tremors, partial paralysis, and coma. These effects were accompanied by 

histopathological changes in the brain in both humans and animals. The symptoms that occur at the 

lowest levels (such as headache, irritability, drowsiness, and tremors) may be considered biomarkers for 

the neurological effects of 1,2-dichloroethane. However, these suggested biomarkers of effects are 

nonspecific to 1,2-dichloroethane-induced toxicity. 

Liver damage is a prominent feature of 1,2-dichloroethane exposure. Biomarkers for hepatotoxicity 

observed in humans and animals were alkylation of hepatocellular macromolecules, increased liver 

weight, and elevated levels of serum enzymes (ALT, AST, SDH). Kidney damage is another major effect 

of 1,2-dichloroethane; kidney failure has been reported in humans following high-level exposure. 

Biomarkers of renal effects in humans and animals included binding of macromolecules in renal cells and 

increased kidney weight. Glomerular involvement may be indicated by urinary excretion of the 

glomerular structural protein fibronectin (Bundschuh et al. 1993). Discussions of additional biomarkers 

of immunological, neurological, hepatic, and renal effects that may be relevant for 1,2-dichloroethaneinduced toxicity can be found in the CDC/ATSDR (1990) and OTA (1990) reports referenced in 

Chapter 9. 

3.9 INTERACTIONS WITH OTHER CHEMICALS 

No studies regarding interactions of 1,2-dichloroethane with other chemicals in humans were located. 

Based on metabolic data resulting from animal studies, various interactions can be expected to occur. 

Inducers and inhibitors of cytochrome P-450 enzymes, glutathione precursors and depleting agents, and 

dietary/nutritional status can all influence the rate of formation and excretion of the various toxic 

intermediates resulting from exposure to 1,2-dichloroethane. 

Induction of hepatic cytochrome P-450 enzymes by phenobarbital and/or Aroclor 1254 increases the rate 

of MFO metabolism of 1,2-dichloroethane in vitro (Hayes et al. 1973; Sipes and Gandolfi 1980). 

Alterations in metabolism could potentially produce profound effects on toxicity. Enhanced enzymatic 
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metabolism of 1,2-dichloroethane also occurs after treatment with ethanol in vitro (Sato et al. 1981). 

Ethanol is an inducer of cytochrome P-450 2E1, the major MFO enzyme involved in 1,2-dichloroethane 

metabolism (Guengerich et al. 1991). However, the effect of the consumption of ethanol before in vitro 

exposure to 1,2-dichloroethane varies greatly depending on the actual tissue concentration of ethanol 

reached during the metabolism of 1,2-dichloroethane (Sato et al. 1981). At low tissue ethanol 

concentration, cytochrome P-450 activity is stimulated. At high tissue ethanol concentrations, especially 

just before exposure to 1,2-dichloroethane, suppression of 1,2-dichloroethane metabolism occurs (Sato et 

al. 1981). Metabolism of 1,2-dichloroethane (50 ppm in air) was unaffected by chronic co-exposure to 

ethanol (5% in drinking water) in a 2-year study in rats (Cheever et al. 1990). Toxicity was also 

unaffected in this study. 

Concurrent administration of 0.15% disulfiram in the diet and inhaled 1,2-dichloroethane (10, 153–304, 

455 ppm) in animals markedly increased hepatotoxicity much more than would occur with exposure to 

1,2-dichloroethane alone (Igwe et al. 1986a, 1988). Similarly, after chronic co-treatment with 50 ppm of 

1,2-dichloroethane by inhalation and 0.05% disulfiram in the diet for 2 years, a series of neoplastic 

lesions were produced in rats that were not produced by 1,2-dichloroethane (or disulfiram) alone 

(Cheever et al. 1990). The lesions included intrahepatic bile duct cholangiomas, subcutaneous fibromas, 

hepatic neoplastic nodules, interstitial cell tumors in the testes, and mammary adenocarcinomas. 

Metabolism studies on rats co-exposed to 1,2-dichloroethane and disulfiram for 2 years showed that 

following a 7-hour exposure, blood levels of 1,2-dichloroethane were elevated five-fold by co-treatment 

with disulfiram (Cheever et al. 1990). In addition, the amount of 14C eliminated as unchanged 

1,2-dichloroethane in the breath was elevated by disulfiram co-treatment, with a corresponding decrease 

in the amount of radioactivity excreted as metabolites in the urine. These results support the suggestion 

that disulfiram reduces the MFO metabolism of 1,2-dichloroethane, leading to accumulation of 

1,2-dichloroethane in the blood and toxic effects. Diethyldithiocarbamate, the reduced form of 

disulfiram, is a relatively selective inhibitor of cytochrome P-450 2E1, the primary MFO enzyme 

involved in 1,2-dichloroethane metabolism (Guengerich et al. 1991). 

Conjugation with glutathione is an important metabolic pathway for 1,2-dichloroethane. However, 

glutathione conjugation with 1,2-dichloroethane has also been hypothesized to produce reactive sulfur 

half-mustard metabolites, such as S-(2-chloroethyl) glutathione (D'Souza et al. 1987; Igwe et al. 1986b; 

Jean and Reed 1989; Lock 1989; Reitz et al. 1982). There is considerable evidence supporting the 

hypothesis that reactive intermediates formed by glutathione conjugation are responsible for 1,2-dichloro­
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ethane toxicity. However, studies also show a protective effect of glutathione. The administration of 

glutathione, precursors of glutathione, or amino acids capable of donating a sulfhydryl group for the 

biosynthesis of glutathione all decrease the toxic effects and mortality in rats given 1,2-dichloroethane 

orally (Heppel et al. 1947). This protective action of glutathione and precursors also occurs in young rats 

exposed to 1,2-dichloroethane by inhalation (Johnson 1967). It is not clear how the protective effect of 

glutathione reported in these studies may be reconciled with the hypothesis that reactive intermediates 

formed by glutathione conjugation are responsible for 1,2-dichloroethane-induced toxicity. By analogy 

to 1,2-dibromoethane, however, the protective effect of co-administered glutathione in 1,2-dichloroethane 

exposures might be explained by the reaction of S-(2-chloroethyl)glutathione with glutathione, which is a 

nonenzymatic reaction occurring at physiological glutathione concentrations (Cmarik et al. 1990), 

although work with 1,2-dibromoethane indicates that levels of DNA adducts are correlated with 

glutathione content (Kim and Guengerich 1990). Methionine, p-aminobenzoic acid, aniline, and 

sulfanilamide have been shown to protect against toxicity of 1,2-dichloroethane (Heppel et al. 1945). A 

good correlation has been found between the urinary excretion of mercapturic acid and the formation of 

DNA adducts in liver and kidney DNA of 1,2-dibromoethane-treated rats (Kim and Guengerich 1989). 

This finding suggests that the extent of formation of adducts may be correlated with the toxic effects of 

1,2-dichloroethane. 

Nutritional status affects the rate of metabolic formation of toxic intermediates; liver from fasted animals 

showed an increased rate of 1,2-dichloroethane metabolism in vitro (Nakajima and Sato 1979) because 

fasting induces the formation of cytochrome P-450 2E1 (Johansson et al. 1988), the primary MFO 

enzyme involved in oxidation of 1,2-dichloroethane (Guengerich et al. 1991). Fasting also may lower 

hepatic levels of glutathione. According to the hypothesis that reactive intermediates formed by 

glutathione conjugation are responsible for 1,2-dichloroethane-induced toxicity, toxicity would be 

reduced under these conditions. However, the actual effect of fasting on 1,2-dichloroethane toxicity is 

unknown. 

A few studies that investigated the toxic interactions between 1,2-dichloroethane and other xenobiotic 

toxicants were located. Pretreatment with orally administered 2-hexanone did not potentiate the 

nephrotoxicity of 1,2-dichloroethane administered by intraperitoneal injection in rats (Raisbeck et al. 

1990). Co-treatment with 1,1-dichloroethylene produced only a slightly greater-than-additive effect on 

lipid droplet changes in rat hepatocytes (EPA 1989b). A mixture of 1,2-dichloroethane (80 mg/kg) and 

carbon tetrachloride (200 mg/kg) administered in a single oral dose to rats produced lower liver 

triglyceride levels than observed with carbon tetrachloride alone. These levels were still increased above 
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1,2-dichloroethane-only levels (Aragno et al. 1992). Studies of in vitro interactions produced more 

positive results. tert-Butyl hydroperoxide potentiated lipid peroxidation induced by 1,2-dichloroethane in 

rat liver slices in vitro (Sano and Tappel 1990). The occurrence of lipid peroxidation is associated with 

physical damage to tissues. There was a synergistic inactivation of plasma alpha-1 proteinase inhibitor 

when 1,2-dichloroethane was tested together with the cigarette smoke components acrolein and pyruvic 

aldehyde in vitro (Ansari et al. 1988b). Inactivation of plasma alpha-1 proteinase inhibitor has been 

proposed as an important factor in the development of lung emphysema. 

Oral administration of 1,2-dichloroethane in drinking water for 16 weeks together with 3 other chemical 

carcinogens commonly found at hazardous waste sites (arsenic, vinyl chloride, and trichloroethylene) 

resulted in inhibition of the promotion of preneoplastic hepatic lesions and pulmonary hyperplasia and 

adenomas (Pott et al. 1998). The four chemicals, including 1,2-dichloroethane, have been shown to be 

individually carcinogenic in laboratory animals, yet they interacted antagonistically to inhibit promotion 

of precancerous lesions. The study is limited, however, by a short exposure duration, small numbers of 

test animals, and the use of only male rats; the interactive effect of lifetime exposure to the four chemicals 

cannot be inferred with confidence from these results. The mechanism for this interactive effect has not 

been elucidated, but Pott et al. (1998) hypothesized that decreased cell proliferation, increased apoptosis, 

or enhanced remodeling of preneoplastic lesions may play a role. 

3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE 

A susceptible population will exhibit a different or enhanced response to 1,2-dichloroethane than will 

most persons exposed to the same level of 1,2-dichloroethane 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 1,2-dichloroethane, or 

compromised function of organs affected by 1,2-dichloroethane. Populations who are at greater risk due 

to their unusually high exposure to 1,2-dichloroethane are discussed in Section 6.7, Populations With 

Potentially High Exposures. 

The synergistic effect of disulfiram (tetraethylthiuram disulfide) on 1,2-dichloroethane hepatotoxicity and 

carcinogenicity in animal studies suggests that individuals exposed concurrently to 1,2-dichloroethane 

and disulfiram, either in the rubber industry or medically (disulfiram is used as an anti-alcohol-abuse 

drug), have increased risk for liver toxicity (Cheever et al. 1990; Igwe et al. 1986a). Disulfiram and its 

reduced form, diethyldithiocarbamate, are known inhibitors of microsomal MFO enzyme, particularly 
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3. HEALTH EFFECTS 

cytochrome P-450 2E1 (Guengerich et al. 1991; Igwe et al. 1985). It is possible that people exposed to 

other MFO inhibitors of like specificity would be at similar risk. 

Inactivation of plasma alpha-1-proteinase inhibitor has been proposed to be an important factor in the 

development of lung emphysema. The occurrence of a synergistic inactivation of plasma alpha-1 

proteinase inhibitor by 1,2-dichloroethane and cigarette smoke components (acrolein and pyruvic 

aldehyde) in vitro suggests that smokers as well as those exposed to passive smoke may be more 

susceptible to lung emphysema following repeated exposure to 1,2-dichloroethane (Ansari et al. 1988b). 

Further, those with genetically reduced plasma alpha-1-proteinase inhibitor, who are predisposed to 

emphysema, may be at increased risk. 

3.11 METHODS FOR REDUCING TOXIC EFFECTS 

This section will describe clinical practice and research concerning methods for reducing toxic effects of 

exposure to 1,2-dichloroethane. 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 1,2-dichloroethane. 

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 1,2-dichloroethane: 

Ellenhorn, M.J. 1997. Ellenhorn’s Medical Toxicology: Diagnosis and Treatment of Human 

Poisons. (2nd ed). Williams and Wilkins, Baltimore. 2047 pp. 

The following discussion is based on suggested treatments provided in Ellenhorn (1997) for patients who 

were exposed to halogenated solvents, including 1,2-dichloroethane. Treatment is largely supportive. 

After dermal or ocular exposure, the exposed surface should be washed immediately with large amounts 

of water; for the eye, a 15- to 20-minute rinse is suggested. Appropriate and timely administration of 

ipecac to induce vomiting may help to reduce absorption from the gut if administered within 1 or 2 hours 

after the halogenated solvent is ingested. However, the risk of aspiration of the chemical during vomiting 

should be considered, particularly for infants and small children. After inhalation exposure, provide 

oxygen and watch for the need to provide mechanical respiration. 

After exposures to high levels of a halogenated solvent, including 1,2-dichloroethane, the patient should 

be monitored for respiratory depression, hypoxic encephalopathy, cardiac dysrhythmias, hepatotoxicity, 

and renal toxicity (Ellenhorn 1997). Blood gases should be monitored and good ventilation maintained. 
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3. HEALTH EFFECTS 

Observe for cardiac arrhythmias for a minimum of 24 hours. In the event of a ventricular arrhythmia, 

lidocaine or beta-blockers could be administered. Monitor serum creatinine, hepatic aminotransferase, 

electrolytes, and fluid balance for signs of hepatic or renal failure. Dialysis may be helpful in the event of 

renal failure. Hepatic failure may be treated with fresh frozen plasma, vitamin K, low protein diet, 

neomycin, and lactulose. 

A major metabolic pathway of 1,2-dichloroethane involves conjugation with glutathione. In apparent 

opposition to the observation that conjugation with glutathione mediates 1,2-dichloroethane toxicity, 

some evidence from animal studies (Heppel et al. 1947; Johnson 1967) suggests that, after acute oral or 

inhalation exposure to 1,2-dichloroethane, prompt oral administration of glutathione, precursors of 

glutathione, or amino acids involved in donating a sulfhydryl group for the biosynthesis of glutathione 

may help to reduce the toxic effects of 1,2-dichloroethane exposure (further details of the animal studies 

are provided in Section 3.9). Ellenhorn (1997) suggested that treatment with N-acetylcysteine may help 

to restore depleted glutathione after exposure to a halogenated solvent, although he noted that no clinical 

trials had been conducted to confirm the efficacy or safety of this treatment. 

3.11.1 Reducing Peak Absorption Following Exposure 

Methods for reducing peak absorption of 1,2-dichloroethane after oral exposure include gastric lavage 

with activated charcoal, administration of ipecac to induce emesis, and the use of cathartics (Ellenhorn 

and Barceloux 1988). No information regarding ways to reduce absorption after exposure by other routes 

was located. 

3.11.2 Reducing Body Burden 

1,2-Dichloroethane is rapidly eliminated from the body after exposure. In animals, excretion of 

1,2-dichloroethane and its metabolites was essentially complete within 48 hours of exposure (see 

Section 3.4.4). Following inhalation or oral exposure, elimination of 1,2-dichloroethane occurred 

primarily via excretion of soluble metabolites in the urine and excretion of unchanged parent compound 

and carbon dioxide in the expired air (Reitz et al. 1982). Increasing the volume of urine production by 

consuming a large volume of fluids beginning shortly after exposure may enhance the rate of urinary 

excretion of soluble 1,2-dichloroethane metabolites. The available data suggest that 1,2-dichloroethane 

will not accumulate in nonlipid components of the human body, but that it may accumulate to some extent 

in adipose tissue and in the breast milk of nursing women. Excretion of 1,2-dichloroethane may be 
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3. HEALTH EFFECTS 

facilitated in nursing women by removing milk using either manual expression or a breast pump. The 

expressed breast milk should be discarded and not fed to infants. Methods (not specified) to enhance 

removal of 1,2-dichloroethane from the body have not been successful (Ellenhorn and Barceloux 1988). 

3.11.3 Interfering with the Mechanism of Action for Toxic Effects 

The mechanism by which 1,2-dichloroethane produces toxic effects is not entirely understood. The two 

important metabolic pathways for 1,2-dichloroethane both lead to the formation of potentially reactive 

intermediates—chloroacetaldehyde by MFO and S-(2-chloroethyl)glutathione by glutathione conjugation 

(see Section 3.4.3). These reactive intermediates could produce toxic effects by binding covalently to 

cellular macromolecules. The MFO biotransformation pathway is saturable, and it has been suggested 

that 1,2-dichloroethane-induced toxicity occurs when MFO metabolism is saturated and large amounts of 

1,2-dichloroethane conjugate with glutathione (see Section 3.5.1). 

If this hypothesis is correct, then stimulation of MFO metabolism might prove effective in reducing 

toxicity. Cytochrome P-450 2E1 is the specific MFO enzyme that catalyzes metabolism of 1,2-dichloroethane (Guengerich et al. 1991). Theoretically, a drug that very rapidly induces this enzyme and is 

administered in a timely manner might have the ultimate effect of reducing 1,2-dichloroethane toxicity. 

Although experimental data are lacking that show that rapid P-450 2E1 induction by another chemical 

reduces 1,2-dichloroethane toxicity, available data do provide indirect support of this argument. Cotreatment with disulfiram, an inhibitor of MFO metabolism (especially P-450 2E1), enhances the toxicity 

of 1,2-dichloroethane (see Section 3.10). Alternatively, administration of drugs that would compete for 

glutathione and reduce the amount of glutathione available to conjugate with 1,2-dichloroethane might 

also mitigate the toxicity of 1,2-dichloroethane. 

However, as evidence of the complexity of 1,2-dichloroethane biotransformation and uncertainty 

regarding toxic mechanisms, it may be noted that co-administration of glutathione and precursors with 

1,2-dichloroethane had a protective effect (Heppel et al. 1947; Jaeger et al. 1974; Johnson 1967). These 

results are the opposite of those expected from the hypothesis that glutathione-dependent metabolites are 

responsible for 1,2-dichloroethane-induced toxicity. Clearly, a greater understanding of 1,2-dichloroethane bioactivation is necessary to develop methods to interfere with the process. 
1,2-DICHLOROETHANE 129 

3. HEALTH EFFECTS 

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 1,2-dichloroethane is available. Where adequate 

information is not available, ATSDR, in conjunction with the National Toxicology Program (NTP), is 

required to assure the initiation of a program of research designed to determine the health effects (and 

techniques for developing methods to determine such health effects) of 1,2-dichloroethane. 

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 1,2-Dichloroethane 

The existing data on health effects of inhalation, oral, and dermal exposure of humans and animals to 

1,2-dichloroethane are summarized in Figure 3-5. The purpose of this figure is to illustrate the existing 

information concerning the health effects of 1,2-dichloroethane. 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 (ATSDR 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. 

Limited information is available on the effects of inhaled 1,2-dichloroethane in humans. Most of the 

information consists of case reports of accidental or occupational exposure to 1,2-dichloroethane vapor. 

These studies are difficult to interpret because exposure concentration usually was not quantified, dermal 

exposure to 1,2-dichloroethane was also likely to occur concurrently with inhalation exposure, thereby 

contributing to total dose, or co-exposure to other chemicals occurred. The human health effects 

associated with ingested 1,2-dichloroethane are reported in case studies of individuals who drank 

1,2-dichloroethane either intentionally or accidentally. In almost all of the case studies, death occurred 
1,2-DICHLOROETHANE 130 

3. HEALTH EFFECTS 

Figure 3-5. Existing Information on Health Effects of 1,2-Dichloroethane 
 

1,2-DICHLOROETHANE 131 

3. HEALTH EFFECTS 

within a few days following exposure, and many of the systemic effects observed were found upon 

autopsy. No evidence of a relationship between 1,2-dichloroethane and cancer has been reported in 

epidemiological studies of petrochemical and other chemical industry workers, but the relevance of these 

studies to 1,2-dichloroethane is limited because exposure to various other chemicals also occurred. 

Similarly, evidence that 1,2-dichloroethane in drinking water is associated with colon and rectal cancer is 

also limited by the co-exposure to other chemicals. No information regarding human health effects 

following dermal exposure to 1,2-dichloroethane, except for ocular effects produced by direct contact 

with the vapor during inhalation exposure was located. 

The lethal and systemic effects of 1,2-dichloroethane following acute- and intermediate-duration 

inhalation exposures have been studied in a variety of species. Excessive mortality was noted in most 

species examined under these exposure durations. Health effects associated with chronic-duration 

inhalation exposure to 1,2-dichloroethane have been investigated only in rats. Lethal and systemic effects 

of oral exposure have been studied mainly in rats and mice exposed for acute, intermediate, and chronic 

durations. Animal health effects data for dermal exposure to 1,2-dichloroethane are only available for 

acute-duration exposure. The carcinogenic effects of 1,2-dichloroethane have been investigated in rats 

and mice following inhalation, oral, and dermal exposure. Based on the results of available animal 

studies, EPA has classified 1,2-dichloroethane as a possible human carcinogen (Group B2) (IRIS 2001). 

3.12.2 Identification of Data Needs 

Acute-Duration Exposure. A data need to conduct additional studies via inhalation, oral, and 

dermal exposure has been identified. Information on 1,2-dichloroethane toxicity in humans comes 

primarily from a few case reports of humans who died following acute exposure to high levels of 

1,2-dichloroethane by inhalation or ingestion (Garrison and Leadingham 1954; Hubbs and Prusmack 

1955; Hueper and Smith 1935; Lochhead and Close 1951; Martin et al. 1969; Nouchi et al. 1984; 

Schönborn et al. 1970; Yodaiken and Babcock 1973). Information that may be obtained from such 

studies is limited, but for 1,2-dichloroethane, the data were sufficient to identify the central nervous 

system, liver, kidney, and possibly cardiovascular system as target organs of high-level exposure from 

both oral and inhalation exposure. Results from acute inhalation and oral exposure studies in animals 

generally support the observations in humans. The dose spacing in these animal studies, however, was 

wide and resulted in identification of NOAELs and serious LOAELs for these effects. 
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3. HEALTH EFFECTS 

The immune system was identified as the most sensitive target in mice for acute gavage exposure 

(Munson et al. 1982) and acute inhalation exposure (Sherwood et al. 1987) to 1,2-dichloroethane, but was 

not affected in rats by acute inhalation exposure to up to 20-fold higher concentrations of 1,2-dichloroethane (Sherwood et al. 1987). The lack of species concordance in the inhalation study in mice and rats 

(Sherwood et al. 1987) suggested that extrapolation from animals to humans is uncertain. The massive 

streptococcal challenge and lethality end point used to measure immune response in the mice exposed by 

inhalation does not appear to be suitable as the basis for MRL derivation. Therefore, an acute-duration 

inhalation MRL was not derived. Only one end point showed a significant dose-related immunotoxic 

effect in the acute gavage study in mice (Munson et al. 1982), and the higher doses of 1,2-dichloroethane 

administered in the drinking water for 90 days were not immunosuppressive in mice (Munson et al. 

1982). These findings precluded acute-duration oral MRL derivation. Additional studies are needed to 

characterize the thresholds for acute immunologic effects and for other end points (e.g., central nervous 

system, liver, kidney, cardiovascular) to determine the most sensitive effects of inhalation and oral 

exposure and to investigate whether the immunologic effects in mice can be extrapolated across species. 

The additional data would establish the most appropriate basis for deriving an acute inhalation or oral 

MRL. 

In addition, the reason for the discrepancy in results for immunotoxicity between the acute gavage and the 

intermediate drinking water study (Munson et al. 1982) is unknown. Although the discrepancy may have 

been related to the methods of dosing (gavage versus drinking water), another possible explanation is that 

younger mice are more susceptible than fully adult mice. As discussed in more detail in the section on 

children’s susceptibility, the mice in the acute study were much younger at the time of immune testing 

than were the mice in the intermediate study. 

The primary exposure routes for populations surrounding hazardous waste sites are ingestion of 

contaminated water and inhalation of air contaminated by volatilization of 1,2-dichloroethane from waste 

sites and from contaminated water used as household water. Studies to determine acute thresholds for 

effects induced by oral exposure, especially via drinking water instead of gavage, and to determine acute 

thresholds for effects of inhalation exposure are needed as populations near hazardous waste sites may be 

exposed to this chemical for brief periods by these routes. 

Very little information was located regarding acute toxicity following dermal exposure in humans or 

animals. 1,2-Dichloroethane is well absorbed by this route, both as undiluted chemical and from aqueous 

solution (Morgan et al. 1991), and is expected to produce effects in the same tissues affected by exposure 
 

1,2-DICHLOROETHANE 133 

3. HEALTH EFFECTS 

via other routes. Acute dermal toxicity data are needed because acute dermal exposure to 1,2-dichloroethane (in household water used for bathing and showering) is a likely route of exposure for humans who 

live near hazardous waste sites. 

Intermediate-Duration. A data need to conduct additional studies via inhalation and dermal 

exposure has been identified. There is no information on the health effects of intermediate-duration 

exposure to 1,2-dichloroethane in humans. Available inhalation studies in animals (Heppel et al. 1946; 

Spencer et al. 1951) are adequate for identifying main target organs (essentially the same as those affected 

by acute inhalation and oral exposure in humans and animals), but do not provide a fully adequate basis 

for identifying the most sensitive end points. Limitations in the intermediate-duration inhalation studies 

preclude considering them in MRL derivation. Additional studies to identify toxicity thresholds 

following intermediate-duration inhalation exposure are needed to derive an inhalation MRL specifically 

for intermediate-duration exposure. 

The MRL for intermediate oral exposure is based on a LOAEL of 58 mg/kg/day for kidney effects in rats 

from an adequate 13-week drinking water study in rats and mice (NTP 1991a). In the same drinking 

water study, the most sensitive effect in mice was also renal, but it occurred at a much higher exposure 

level, 249 mg/kg/day (NTP 1991a). A 90-day immunotoxicity study in mice of 1,2-dichloroethane in 

drinking water found no effects on the immune system and no effects on liver or kidney weight at the 

highest exposure level, 189 mg/kg/day. Thus, the rat appears to be more sensitive than the mouse to 

1,2-dichloroethane exposure in drinking water. Although few immune-related end points were evaluated 

in the rat subchronic drinking water study (leukocyte counts, thymus histology), acute inhalation 

exposure did not result in immune effects in rats at exposure levels as much as 20-fold higher than the 

effect levels in mice in the same study (Sherwood et al. 1987). Additional oral studies could identify a 

NOAEL, as well as determine if the kidney is the most sensitive target for intermediate-duration exposure 

to 1,2-dichloroethane (see data needs sections for acute-duration exposure and for immunotoxicity). 

Because the data were adequate for derivation of an intermediate oral MRL, a data need is not identified 

for this route and duration. 

Dermal data were not located, but are needed because absorption by this route is expected (Morgan et al. 

1991), and intermediate-duration dermal exposure is a likely exposure scenario for humans who live in 

the vicinity of a hazardous waste site. 
 

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3. HEALTH EFFECTS 

Chronic-Duration Exposure and Cancer. A data need to conduct additional studies via oral and 

dermal exposure has been identified. There is no information on the noncancer health effects of chronicduration exposure to 1,2-dichloroethane by any route in humans. Chronic studies in animals are limited 

to one inhalation study in rats (Cheever et al. 1990) and one oral study in rats and mice (NCI 1978) that 

were primarily designed to assess carcinogenicity, but provided some information on systemic toxicity. 

The inhalation study (Cheever et al. 1990) was used to derive an MRL for chronic-duration exposure but 

is limited by the use of a single exposure level (a NOAEL), use of a single species, and lack of sensitive 

immunotoxicity end points. Because the inhalation information was considered adequate for MRL 

derivation, there is no data need for additional chronic inhalation studies. 

The oral study (NCI 1978) provided an insufficient basis for derivation of an MRL due to limitations such 

as dosage adjustments, possible contamination by other chemicals tested in the same laboratory, and poor 

survival and small numbers of control animals, as well as concerns regarding the method of exposure, 

since it may not be appropriate to base an MRL on an effect level from a gavage oil study due to 

toxicokinetic considerations (bolus saturation of the detoxification/excretion mechanism, discussed 

elsewhere in this document). Additional chronic oral toxicity studies are needed because they could 

identify critical targets that are different than those detected in shorter-term studies and because toxicity 

levels may be considerably lower than in shorter-term studies. 

The only chronic dermal study in animals was a carcinogenicity study that did not investigate noncancer 

end points (Van Duuren et al. 1979). 

Epidemiological studies that have investigated associations between occupational or oral exposure to 

1,2-dichloroethane and increased incidences of cancer are inadequate for assessing carcinogenicity of 

1,2-dichloroethane in humans due to complicating co-exposures to various other chemicals, as discussed 

in the section on epidemiology. The carcinogenic potential of 1,2-dichloroethane has been examined in 

rats and mice following inhalation, oral, and dermal exposure. No tumors were produced in rats and mice 

exposed to 1,2-dichloroethane via inhalation (Cheever et al. 1990; Maltoni et al. 1980). Limitations of 

the inhalation studies included the use of a single, subthreshold exposure level in one study (Cheever et 

al. 1990) and exceedance of the maximum tolerated dose in rats, less-than-lifetime study duration, and 

poor survival in mice in the other study (Maltoni et al. 1980). 
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3. HEALTH EFFECTS 

1,2-Dichloroethane was carcinogenic after gavage administration (of 97–195 mg/kg/day to rats and 

97–299 mg/kg/day to mice), inducing statistically significant increases in forestomach squamous cell 

carcinomas, hemangiosarcomas, and subcutaneous fibromas in male rats; mammary gland 

adenocarcinomas and hemangiosarcomas in female rats; hepatocellular carcinomas and 

alveolar/bronchiolar adenomas in male mice; and alveolar/bronchiolar adenomas, mammary carcinomas, 

and endometrial tumors in female mice (NCI 1978). Limitations of this oral study include the nonnatural 

method of administration (gavage) and dosage adjustments during the study. 

1,2-Dichloroethane induced lung papillomas following lifetime dermal exposure of female mice (Van 

Duuren et al. 1979). The results showed an apparent dose-response, with statistical significance at the 

high dose. This study appears adequate to demonstrate the carcinogenic potential of dermal exposure to 

1,2-dichloroethane. In addition, pulmonary adenomas have been induced in mice by intraperitoneal 

injection (Stoner 1991; Theiss et al. 1977), and, as discussed previously, by oral administration of 

1,2-dichloroethane. 

It has been suggested that the route-related differences in carcinogenicity between inhalation and oral 

exposure may be associated with saturation of the detoxification/excretion mechanism by gavage dosing. 

Reitz et al. (1982) proposed that 1,2-dichloroethane-induced toxicity occurred when the biotransformation 

processes were saturated, thereby allowing higher levels of 1,2-dichloroethane to circulate throughout the 

body instead of being detoxified and eliminated. The 1,2-dichloroethane inhalation study, therefore, may 

not have produced peak blood levels that were high enough to saturate the detoxification mechanisms and 

produce a detectable incidence of tumors. Metabolic saturation apparently occurs at lower doses after 

oral administration (particularly by gavage) than after inhalation exposure. Additional information on 

1,2-dichloroethane from well-conducted animal bioassays using the natural routes of exposure expected 

for populations surrounding hazardous waste sites (i.e., drinking water ingestion and inhalation exposure) 

are needed to better predict the likelihood of carcinogenicity in humans. 

The positive and suggestive carcinogenicity results from animal bioassays (NCI 1978; Stoner 1991; 

Theiss et al. 1977; Van Duuren et al. 1979), along with data indicating that 1,2-dichloroethane and certain 

metabolites are mutagenic and capable of forming DNA adducts as discussed in the preceding section, 

provide sufficient evidence to suggest that 1,2-dichloroethane is a probable human carcinogen. Because 

oral, dermal, and intraperitoneal exposure of experimental animals to 1,2-dichloroethane is associated 

with the induction of tumors remote from the site of administration, 1,2-dichloroethane should be 

considered potentially carcinogenic by the inhalation route of exposure as well. The DHHS has 
 

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3. HEALTH EFFECTS 

determined that 1,2-dichloroethane may reasonably be anticipated to be a human carcinogen (NTP 2000). 

IARC has placed 1,2-dichloroethane in Group 2B (possibly carcinogenic to humans) (IARC 2001). EPA 

has classified 1,2-dichloroethane as a Group B2 carcinogen (probable human carcinogen) (IRIS 2001). 

This EPA category applies to chemical agents for which there is sufficient evidence of carcinogenicity in 

animals. 

Genotoxicity. A data need to conduct additional genotoxicity studies has been identified. No 

information regarding the genotoxicity of 1,2-dichloroethane in humans following oral, inhalation, 

dermal, or parenteral exposure is available. However, a great deal of data are available regarding the 

genotoxic effects of 1,2-dichloroethane in human cells in vitro; prokaryotic organisms, fungi, and 

nonhuman mammalian cells in vitro; and insects, rats, and mice in vivo. 

The ability of 1,2-dichloroethane to bind to DNA in rats and mice in vivo has been well established, not 

only in the liver, but also in other organs such as the kidney and lung (Baertsch et al. 1991; Banerjee 

1988; Cheever et al. 1990; Hellman and Brandt 1986; Inskeep et al. 1986; Prodi et al. 1986). DNA 

binding has also been reported in D. melanogaster in vivo (Fossett et al. 1995). DNA damage has been 

demonstrated in vivo in mice (Sasaki et al. 1998; Storer and Conolly 1983, 1985; Taningher et al. 1991). 

Genotoxicity assays for clastogenic effects in mice in vivo obtained mixed results, with a positive effect 

on sister chromatid exchange in bone marrow cells (Giri and Hee 1988), but no effect on micronucleus 

formation (Armstrong and Galloway 1993; Jenssen and Ramel 1980; King et al. 1979; Sasaki et al. 1994), 

and in D. melanogaster, gave positive results for chromosomal aberration (Ballering et al. 1993) and a 

marginally positive response for chromosomal recombination (Rodriguez-Arnaiz 1998). Negative results 

were obtained in a cell transformation assay (Milmann et al. 1988). 

The only in vivo assay for the mutagenicity of 1,2-dichloroethane in mammalian cells (mouse/spot test) 

produced a marginal response (Gocke et al. 1983), and a mouse host-mediated assay produced negative 

results in Escherichia coli (King et al. 1979). However, there is abundant evidence that 1,2-dichloroethane produces both somatic and sex-linked recessive lethal mutations in D. melanogaster in vivo 

(Ballering et al. 1994; King et al. 1979; Kramers et al. 1991; Nylander et al. 1978; Romert et al. 1990; 

Vogel and Nivard 1993). In addition, in vitro studies provide strong support for the mutagenicity of 

1,2-dichloroethane. Results of in vitro assays for point mutations were positive in human cells (Crespi et 

al. 1985; Ferreri et al. 1983), marginally positive in a single assay in animal cells (Tan and Hsie 1981), 

and positive in nearly all of the assays in bacteria, with or without metabolic activation (Barber et al. 

1981; Brem et al. 1974; Buijs et al. 1984; Cheh et al. 1980; Hemminki et al. 1980; Kanada and Uyeta 
1,2-DICHLOROETHANE 137 

3. HEALTH EFFECTS 

1978; King et al. 1979; Milman et al. 1988; Moriya et al. 1983; Nestmann et al. 1980; Rannug and Beije 

1979; Rannug et al. 1978; Roldan-Arjona et al. 1991; Simula et al. 1993; Thier et al. 1993; Van Bladeren 

et al. 1981), although not in a single assay in fungi (Crebelli and Carere 1988). The results of these 

bacterial mutagenicity assays suggest that 1,2-dichloroethane is a very weak, direct-acting mutagen that 

can be activated to a more effective species by glutathione and glutathione S-transferases (DeMarini and 

Brooks 1992). 

Additional evidence from in vitro studies supports the in vivo results regarding the DNA binding, DNA 

damaging, and clastogenic effects of 1,2-dichloroethane. Results were positive for DNA binding in 

animal cells (Banerjee 1988; Banerjee and Van Duuren 1979; Banerjee et al. 1980; Prodi et al. 1986), 

unscheduled DNA synthesis (i.e., DNA repair activity) in human (Perocco and Prodi 1981) and animal 

cells (Milman et al. 1988; Williams et al. 1989), and mitotic segregation aberrations leading to aneuploidy 

in fungi (Crebelli et al. 1984). Negative results were obtained for intrachromosomal recombination in a 

single assay in animal cells (Zhang and Jenssen 1994, but positive results were reported for micronucleus 

formation in human cells (Doherty et al. 1996; Tafazoli et al. 1998). Thus, both in vitro and in vivo 

genotoxic effects of 1,2-dichloroethane include gene mutations, DNA binding and damage, and 

clastogenic effects. 

The DNA binding is an alkylation of DNA that occurs following biotransformation of 1,2-dichloroethane. 

Inhalation exposure of rats to very high concentrations of 1,2-dichloroethane for short durations produced 

greater amounts of DNA binding in liver and lung than do longer-duration inhalation to low 

concentrations (Baertsch et al. 1991), and oral gavage doses were more potent in causing DNA damage in 

liver than were comparable inhalation doses in mice (Storer et al. 1984). These observations are 

consistent with the hypothesis that the toxicity of 1,2-dichloroethane is associated with saturation of MFO 

enzymes. The major identified DNA adduct is S-[2-(N7

-guanyl)ethyl]glutathione in rat liver following a 

single intraperitoneal injection of 14C-1,2,-dichloroethane, and it is one of several DNA adducts found in 

the kidney, after a single intraperitoneal injection (Inskeep et al. 1986). 

Although genotoxicity in humans could be investigated directly by examining peripheral lymphocytes 

obtained from exposed workers for clastogenic effects, the utility of such studies is likely to be limited 

due to the workers’ exposures to other chemicals. Additional in vivo studies examining the importance of 

the route of administration on 1,2-dichloroethane-induced quantitative genotoxicity data (i.e., adducts) in 

animals are needed since the available information indicates route-dependent effects (inhalation doses are 

less potent than oral gavage) (Storer et al. 1984). DNA adduct and monoclonal antibody dosimetry work 
 

 

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also are needed to provide quantitative genotoxicity data, and perhaps could be used as a biomarker of 

exposure to 1,2-dichloroethane. 

Reproductive Toxicity. A data need to conduct additional reproductive studies via dermal exposure 

has been identified. A single study on reproductive effects of exposure to 1,2-dichloroethane in humans 

is suggestive of a decrease in duration of gestation (Zhao et al. 1989), but should be interpreted with 

caution since co-exposure to other chemicals occurred in most cases and the adequacy of the study design 

could not be evaluated because of reporting deficiencies. Results of animal studies indicate that this 

chemical is unlikely to cause female reproductive impairment at doses that are not maternally toxic. 

Although some inhalation studies found that exposure to 1,2-dichloroethane prior to mating and 

continuing into gestation caused pre-implantation loss and embryolethality in rats (Vozovaya 1974, 1977; 

Zhao et al. 1989), the methods used by these investigators were not well reported and the reliability of the 

data is uncertain. In contrast to these findings, a well-designed and reported study of reproductive 

toxicity found no adverse effects on the fertility of rats exposed by inhalation to 10-fold higher 

concentrations of 1,2-dichloroethane in a one-generation reproduction study (Rao et al. 1980). In the 

absence of an apparent explanation for the discrepancy, greater credence should be given to the welldesigned and reported study. One- and two-generation reproduction studies found no chemical-related 

effects on fertility indices in long-term oral studies in mice and rats (Alumot et al. 1976; Lane et al. 1982), 

but exposure to higher oral doses caused increases in nonsurviving implants and resorptions in rats that 

also experienced maternal toxicity (30% decreased body weight gain) (Payan et al. 1995). Histological 

examinations of the testes, ovaries, and other male and female reproductive system tissues were 

performed in intermediate- and chronic-duration inhalation and oral animal studies with negative results 

(Cheever et al. 1990; Daniel et al. 1994; NCI 1978; NTP 1991a; van Esch et al. 1977), although 

reproductive performance was not evaluated in these studies. 

Although 1,2-dichloroethane appears to have induced embryotoxic effects in one adequate animal study 

conducted by the oral route, the overall indication of the data is that this chemical is unlikely to impair 

reproduction at doses that are not highly toxic. No data are available regarding the potential reproductive 

toxicity of dermal exposure, so there is a need for studies. 

Developmental Toxicity. A data need to conduct additional developmental studies via inhalation, 

oral, and dermal exposure has been identified. The only studies regarding developmental effects in 

humans are epidemiologic investigations of adverse birth outcomes that found increased OR for exposure 

to 1,2-dichloroethane in public drinking water and major cardiac defects (but not neural tube defects) 
 

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(Bove 1996; Bove et al. 1995), and for residence within the census tract of NPL sites contaminated with 

1,2-dichloroethane and neural tube defects (but not heart defects) (Croen et al. 1997). Primary routes of 

exposure in these epidemiologic studies may have been both oral and inhalation (including inhalation of 

1,2-dichloroethane volatilized from household water). The OR for cardiac defects for 1,2-dichloroethane 

(detected versus not detected in drinking water) was 2.8 (95% CI 1.11–6.65; 6 exposed cases) (Bove 

1996; Bove et al. 1995). The crude odds ratio for neural tube defects was 2.8 (95% CI 1.0–7.2; 

14 exposed cases) (Croen et al. 1997). In these studies, the study populations were also simultaneously 

exposed to elevated levels of other contaminants. Because of the mixed chemical exposure, lack of doseresponse information, and inconsistency between the findings of the two studies, the associations with 

1,2-dichloroethane are only suggestive, do not establish a cause-and-effect relationship, and should be 

interpreted with caution. 

The weight of evidence from available inhalation and oral studies in rats, mice, and rabbits indicates that 

1,2-dichloroethane is not fetotoxic or teratogenic, although indications of embryo and fetal lethality at 

maternally toxic doses have been reported (Kavlock et al. 1979; Lane et al. 1982; Payan et al. 1995; Rao 

et al. 1980). The reliability of the reports of increased embryo and pup mortality following intermediateduration inhalation of lower (not maternally toxic) concentrations of 1,2-dichloroethane (Vozovaya 1977; 

Zhao et al. 1989) is uncertain, due to the lack of statistical analysis, inadequate description of methods, 

and uncertainties in the reported results. The possibility of induction of cardiac malformations by 

1,2-dichloroethane, as suggested by the epidemiologic data, was not adequately addressed in the animal 

studies because their conventional teratology protocols did not include detailed examinations of dissected 

hearts. Given the suggestive evidence of an association between exposure to 1,2-dichloroethane in 

drinking water and major cardiac defects in human offspring, and evidence of heart malformations in 

epidemiology and animal cardiac teratogenicity studies of dichloroethylene and trichloroethylene 

(Dawson et al. 1993; Goldberg et al. 1990), which are metabolized to some of the same reactive 

intermediates as is 1,2-dichloroethane, it would be informative to have studies specifically designed to 

investigate the potential for induction of developmental heart malformations by 1,2-dichloroethane. In 

addition, the possibility of neurodevelopmental effects, also suggested by the epidemiological data, needs 

to be investigated, particularly because 1,2-dichloroethane is known to affect the central nervous system. 

Immunotoxicity. A data need to conduct additional immunotoxicity studies via inhalation, oral, and 

dermal exposure has been identified. Immunological effects reported in humans exposed to 1,2-dichloroethane are limited to splenic lesions in a single case of accidental ingestion (Hubbs and Prusmack 1955). 

In mice, this chemical had immunosuppressive effects following both acute inhalation and acute oral 
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3. HEALTH EFFECTS 

exposure. A single 3-hour inhalation exposure to 5 or 11 ppm increased the susceptibility of female mice 

to bacterial infection, and to 11 ppm decreased the bactericidal activity of the lungs. No change in 

bactericidal activity was seen in male rats after a single 5-hour inhalation exposure to 200 ppm or 

12 5-hour exposures to 100 ppm (Sherwood et al. 1987). Other immune function end points studied in 

the rats were also negative. The relevance of the end point (lethality due to massive streptococcal 

challenge) in mice to immune function is known, but its suitability as a basis for MRL derivation is 

uncertain. Gavage administration of 4.9 and 49 mg/kg/day of 1,2-dichloroethane to mice for 14 days 

reduced humoral (immunoglobulin response to sheep red blood cells) and cell-mediated (delayed-type 

hypersensitivity response to sheep erythrocytes) immunity. Only the humoral response was dose-related. 

In addition, the leukocyte number was decreased by 30% at the high dose (Munson et al. 1982). The 

immune system was the most sensitive target for short-term exposure to 1,2-dichloroethane by both the 

inhalation and gavage routes in mice, as compared with end points in other studies in mice and in other 

species. The other studies, however, had limitations including wide spacing of the exposure 

concentrations, such that only NOAELs and serious LOAELs were identified. 

In contrast to the acute oral study, higher doses of 1,2-dichloroethane (189 mg/kg/day) administered to 

mice in their drinking water for 90 days did not affect humoral and cell-mediated immunity (Munson et 

al. 1982), as assessed by some of the Tier I and Tier II procedures from the immunotoxicity testing 

battery (Luster et al. 1988). Immune function has not been evaluated in chronic-duration studies of 

1,2-dichloroethane, but histopathological examinations failed to detect immune system lesions or 

immune-related changes in rats and mice exposed to 1,2-dichloroethane by inhalation or oral (gavage or 

drinking water) routes for intermediate or chronic durations (Cheever et al. 1990; NCI 1978; NTP 1991a). 

Leucocyte counts were not affected in intermediate-duration drinking water and gavage studies in rats 

(NTP 1991a). The acute data provide limited evidence that the immune system is a sensitive target of 

1,2-dichloroethane in mice, but not rats. Because of the apparent interspecies differences in animal 

immunotoxicity, it is unclear whether the immune system could be a target of 1,2-dichloroethane in 

humans following acute exposure by inhalation or ingestion. 

The mechanism by which 1,2-dichloroethane may produce immunological effects is not known, but it is 

possible that these effects were produced by reactive intermediates resulting from conjugation with 

glutathione (Reitz et al. 1982). Glutathione conjugation and MFO metabolism are the two primary 

pathways of 1,2-dichloroethane metabolism. It has been shown that MFO metabolism of 1,2-dichloroethane is saturable and that direct glutathione conjugation occurs to a much greater extent after saturation 

of MFO metabolism. Gavage administration, which involves the placement of large bolus doses in the 
 

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3. HEALTH EFFECTS 

stomach that are absorbed at one time, could lead to saturation of MFO metabolism and the subsequent 

expression of toxicity. Drinking water exposure, which results in multiple daily ingestions of small 

doses, may not provide large enough doses to saturate MFO metabolism, even when the aggregate daily 

dose is fairly large. Therefore, even though immunological effects might be expected in humans 

ingesting large doses of undiluted 1,2-dichloroethane, it is uncertain whether immunological effects 

would occur in humans exposed to 1,2-dichloroethane in the drinking water at hazardous waste sites. 

Another possible explanation for the different outcomes of acute and intermediate oral exposure is that 

1,2-dichloroethane may induce its own metabolism during the longer exposure period, thus reducing the 

dose to the immune cells. An additional possibility, related to age of the mice at the time of immune 

function testing, was mentioned in the section on acute exposure and is discussed in detail in the section 

on children’s susceptibility. 

Both the oral and the inhalation acute immunotoxicity studies found immunosuppressive effects at levels 

of 1,2-dichloroethane low enough to enable identification of the immune system as the most sensitive 

target for acute exposure by both routes of exposure, but neither study provided the data sufficient for 

deriving an MRL (the lethality assay in the inhalation study was not considered suitable, and the oral 

study showed a dose-response in only one end point and was limited by use of gavage). In addition, 

dose-response information for other potential targets of toxicity was not adequate. Additional studies are 

needed to determine the immunologic potential of acute inhalation and oral (drinking water) exposure and 

to better characterize the threshold for immunologic effects by both routes of exposure relative to 

thresholds for other effects in order to provide the data needed to establish the most appropriate basis for 

deriving acute inhalation and oral MRLs. 

No data were located regarding the potential immunotoxicity of dermal exposure. 

Neurotoxicity. A data need to conduct additional neurotoxicity studies via inhalation, oral, and 

dermal exposure has been identified. Neurological symptoms and signs in people acutely exposed to high 

levels of 1,2-dichloroethane by inhalation (Nouchi et al. 1984) or ingestion (Hubbs and Prusmack 1955; 

Lochhead and Close 1951; Yodaiken and Babcock 1973) included headache, irritability, drowsiness, 

tremors, partial paralysis, and coma. Autopsies of people who died following acute exposure to this 

chemical revealed morphological changes in the brain, such as hyperemia, edema, hemorrhage, myelin 

degeneration, diffuse changes in the cerebellum, shrunken appearance and pyknotic nuclei in the Purkinje 

cell layer of the cerebellum, and parenchymous changes in the brain and spinal cord (Hubbs and 
 

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3. HEALTH EFFECTS 

Prusmack 1955; Hueper and Smith 1935; Lochhead and Close 1951; Nouchi et al. 1984). The results of 

animal studies confirm that the central nervous system is a target of high concentrations of 1,2-dichloroethane. Symptoms similar to those reported in humans, such as tremors, abnormal posture, uncertain gait, 

and narcosis, were observed after high-level acute vapor exposures (Heppel et al. 1945; NTP 1991a; 

Spencer et al. 1951). In addition, clinical signs of neurotoxicity and mild necrosis in the cerebellum were 

found in rats administered 240–300 mg/kg/day of 1,2-dichloroethane by gavage for 13 weeks (NTP 

1991a). No clinical signs or neurological lesions were seen in rats exposed through their drinking water 

up to 492 mg/kg/day or mice exposed up to 4,210 mg/kg/day for 13 weeks (NTP 1991a), and no brain 

lesions were seen in rats intermittently exposed to 50 ppm for 2 years (Cheever et al. 1990). No studies 

regarding the potential neurotoxicity of dermal exposure were located. The discrepancy in results 

between gavage and drinking water administration may be due to saturation of the detoxification/ 

excretion mechanism by the bolus gavage dosing. These data do not sufficiently characterize the 

potential for 1,2-dichloroethane to induce more subtle neurotoxic effects following low-level prolonged 

exposure by inhalation, oral, or dermal exposure. Intermediate-duration neurotoxicity studies in animals, 

using sensitive functional and neuropathological tests at inhalation and oral exposure levels significantly 

lower than those resulting in morbidity and death, would assist in the characterization of the neurotoxic 

potential of 1,2-dichloroethane. 

Epidemiological and Human Dosimetry Studies. A data need has been identified. Most of the 

available information on the adverse noncancer effects of 1,2-dichloroethane in humans comes from cases 

of acute poisoning by inhalation or ingestion (Garrison and Leadingham 1954; Hubbs and Prusmack 

1955; Hueper and Smith 1935; Lochhead and Close 1951; Martin et al. 1969; Nouchi et al. 1984; 

Schönborn et al. 1970; Yodaiken and Babcock 1973) and epidemiological studies of exposure to drinking 

water contaminants, residence near hazardous waste sites, or employment in the chemical industry 

(discussed later in this section). Limitations inherent in the case studies include unquantified exposure 

and the high-dose nature of the exposures. Despite their inadequacies, the available human case studies 

indicate that 1,2-dichloroethane can cause neurotoxic, nephrotoxic, and hepatotoxic effects, and death due 

to cardiac arrhythmia. These observations are similar to those in high-dose animal studies, but other, 

more sensitive effects seen in animals at low levels of exposure have not been investigated in humans. 

Epidemiologic investigations of adverse birth outcomes found an increased OR for exposure to 

1,2-dichloroethane in public drinking water and major cardiac defects (but not neural tube defects) (Bove 

1996; Bove et al. 1995), and an increased OR for residence within the census tract of NPL sites 

contaminated with 1,2-dichloroethane and neural tube defects (but not heart defects) (Croen et al. 1997). 
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The study populations also were simultaneously exposed to elevated levels of other contaminants. 

Because of the mixed chemical exposure, lack of dose-response information, and inconsistency between 

the findings of the two studies, the associations with 1,2-dichloroethane are only suggestive, and do not 

establish a cause-and-effect relationship. The animal data do not indicate that 1,2-dichloroethane is 

teratogenic, but conventional teratology protocols were used that do not include detailed examinations of 

dissected hearts. Increased rates of premature births were reported in workers exposed in a Chinese 

synthetic fiber factory (Zhao et al. 1989). The study included women exposed throughout pregnancy and 

unexposed wives of men exposed for at least 1 year before their wives became pregnant, and included 

relatively small numbers of exposed workers. It was generally deficient in reporting of study design and 

accounting for possible confounders, including other chemicals in the factory. In general, the adequate 

one- and two-generation reproductive studies in animals did not report effects except at high, 

maternotoxic exposure levels. 

Epidemiological studies of workers in the chemical industry suggest that exposure to chemical 

manufacturing processes that involve 1,2-dichloroethane is associated with an increased incidence of 

brain tumors (Austin and Schnatter 1983a, 1983b; Reeve et al. 1983; Teta et al. 1989; Waxweiler et al. 

1983), nonlymphatic leukemia (Ott et al. 1989), stomach cancer, and leukemia (Hogstedt et al. 1979), and 

with increased deaths due to pancreatic cancer and lymphatic and hematopoietic cancers (Benson and 

Teta 1993) among chemical plant workers. Increased risk of breast cancer was reported among men 

working at jobs associated with exposure to gasoline or gasoline combustion products containing 

1,2-dichloroethane (Hansen 2000), and the risk of several cancer types was increased in residents living 

proximal to a Montreal municipal waste site that emitted volatile organic substances including 

1,2-dichloroethane (Goldberg et al. 1995). These studies involved exposure to other chemicals and did 

not deal with 1,2-dichloroethane exposure exclusively. Isacson et al. (1985) reported an association 

between the presence of 1,2-dichloroethane in drinking water and an increased incidence of colon and 

rectal cancer in men aged 55 years or older, but other organic chemicals were present in the drinking 

water. Studies in animals are adequate to support the determination that 1,2-dichloroethane may 

reasonably be anticipated to be a human carcinogen. 

Well-controlled epidemiological studies of people living in areas where 1,2-dichloroethane has been 

detected in water or near industries or hazardous waste sites releasing 1,2-dichloroethane, and/or of 

people exposed in the workplace, could add to and clarify the existing database on 1,2-dichloroethaneinduced human health effects. In the United States, however, about 98% of the 1,2-dichloroethane 

produced is used (usually captively) to manufacture vinyl chloride (Anonymous 1998), which is a more 
 

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3. HEALTH EFFECTS 

potent toxicant and carcinogen than is 1,2-dichloroethane. Other uses of 1,2-dichloroethane also involve 

manufacture of other chemicals. Therefore, it may not be possible to identify a cohort of workers 

exposed predominantly to 1,2-dichloroethane. Previous studies of 1,2-dichloroethane from hazardous 

waste sites or drinking water have not been able to establish anything more than a weak association 

between a health effect and 1,2-dichloroethane due to the presence of many other chemicals at the sites or 

in the water, small numbers of cases with the health effect, and difficulties in controlling for all of the 

variables that may confound the results for a general population study. At present, the only known health 

effects of 1,2-dichloroethane in humans, seen in cases of acute high exposure, are neurotoxicity, 

nephrotoxicity, hepatotoxicity, and effects on the cardiovascular system. A particularly sensitive end 

point of acute inhalation or gavage exposure to 1,2-dichloroethane in mice (but not rats) is immunological 

effects. No data regarding this end point are available for humans. 

Biomarkers of Exposure and Effect. 

Exposure. A data need has been identified. Proposed biomarkers for exposure to 1,2-dichloroethane 

include levels of parent compound in the breath, blood, urine, and breast milk; levels of thioethers in the 

urine; and levels of thiodiglycolic acid in the urine (Igwe et al. 1988; Payan et al. 1993; Spreafico et al. 

1980; Urusova 1953). However, use of the parent compound as a biomarker would only be possible soon 

after exposure, and the other proposed biomarkers are not specific for 1,2-dichloroethane. If 

epidemiological studies are conducted in which there is a correlation between 1,2-dichloroethane 

exposure and specific adverse health effects, then it may be possible to correlate these health effects 

quantitatively with changes in tissue and/or body levels of 1,2-dichloroethane. 

Effect. Biomarkers of effect for 1,2-dichloroethane include serum enzyme levels indicative of liver 

damage (ALT, AST, SDH), increased liver or kidney weight (size), and DNA adduct formation for liver 

and kidney effects (Brondeau et al. 1983; Inskeep et al. 1986; Nouchi et al. 1984; Prodi et al. 1986). 

Another potential biomarker would be tests for immunosuppression, but immune effects have been 

demonstrated only in mice in acute exposure studies (Munson et al. 1982; Sherwood et al. 1987). 

Because they have not been seen in humans, rats, or even mice exposed for an intermediate duration, the 

relevance of these effects to humans is uncertain. None of these biomarkers are specific for 1,2-dichloroethane. These biomarkers are indicative of effects, but dosimetry has not been worked out for any of 

them. Because immunological effects of 1,2-dichloroethane have been seen only in mice, it is uncertain 

whether immunosuppression would occur in humans exposed to this chemical. 
 

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Absorption, Distribution, Metabolism, and Excretion. A data need to assess the toxicokinetics 

of 1,2-dichloroethane following inhalation, oral, and dermal exposure has been identified. Case reports of 

toxic effects subsequent to inhalation or oral exposure suggest that 1,2-dichloroethane is absorbed 

following exposure by these routes (Garrison and Leadingham 1954; Hueper and Smith 1935; Lochhead 

and Close 1951; Martin et al. 1969; Nouchi et al. 1984; Schönborn et al. 1970; Yodaiken and Babcock 

1973). Inhalation exposure of lactating women in the workplace resulted in distribution of 1,2-dichloroethane to their milk (Urusova 1953). Animal studies were sufficient to characterize the rate and extent of 

absorption following inhalation, oral, and dermal exposure (Morgan et al. 1991; Reitz et al. 1980, 1982; 

Spreafico et al. 1980). Distribution, metabolism, and excretion have also been well studied in animals 

exposed by the inhalation or oral routes (D'Souza et al. 1987, 1988; Reitz et al. 1982; Spreafico et al. 

1980), and are qualitatively similar across these routes. Metabolism is saturable in animals, but the 

precise levels at which saturation phenomena come into play have not been determined and appear to 

differ between oral (gavage) and inhalation exposures (Reitz et al. 1982). Additional studies investigating 

the saturation of MFO metabolism by inhaled and ingested 1,2-dichloroethane would enable better 

understanding of the metabolism of this compound. Based on the elimination of virtually all radiolabel 

from inhalation or gavage administration of 1,2-dichloroethane to rats within 48 hours, Reitz et al. (1982) 

concluded that the potential for 1,2-dichloroethane to accumulate with repeated exposure is minimal. The 

rate of elimination of the parent compound from adipose tissue was similar to that from blood following 

gavage administration to rats, but was slower following a single inhalation exposure or intravenous 

injection (Spreafico et al. 1980; Withey and Collins 1980), raising the possibility that 1,2-dichloroethane 

may accumulate to some extent in adipose tissue and in breast milk of nursing women. More quantitative 

information on the presence of 1,2-dichloroethane in fat and breast milk would be useful to assess the 

ability of 1,2-dichloroethane to accumulate in fat and the potential hazard to nursing infants. Further 

study into the long-term fate of low-level 1,2-dichloroethane exposure in humans and animals and the 

potential for accumulation in humans would also provide valuable information. 

Toxicity data in humans and animals suggest similar target organs in each. Toxicokinetic studies have 

not been performed in humans. The database with regard to comparative toxicokinetics across species is 

limited as most studies have been performed in rats (D'Souza et al. 1987, 1988; Morgan et al. 1991; Reitz 

et al. 1980, 1982; Spreafico et al. 1980). Only one set of studies included mice (D’Souza et al. 1987, 

1988), and these studies were conducted to validate PBPK modeling, primarily for levels of the direct 

GSH conjugate in selected tissues of concern for carcinogenicity (liver and lung). More information on 

the toxicokinetics of 1,2-dichloroethane in other animal species would be useful for more fully assessing 

interspecies differences and the implications for human exposure. The database with regard to 
 

 

 

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3. HEALTH EFFECTS 

comparative toxicokinetics across routes does include comparative toxicokinetics across acute inhalation 

and gavage (oil) administration (Reitz et al. 1980; Spreafico et al. 1980). The vehicle used in oral 

administration studies appears to play a role in the time course of absorption. Withey et al. (1983) 

reported that 1,2-dichloroethane is absorbed more rapidly by the gastrointestinal tract following gavage 

administration in water than in corn oil; the estimated area under the curve (based on data for up to 

300 minutes postdosing) was also much greater for the water than the oil vehicle). Information on 

toxicokinetics for repeated or longer-term continuous exposure is not available. 

Comparative Toxicokinetics. Toxicity data in humans and animals suggest similar target organs in 

each. Toxicokinetic studies have not been performed in humans. The database with regard to 

comparative toxicokinetics consists primarily of studies in rodents (D'Souza et al. 1987, 1988; Morgan et 

al. 1991; Reitz et al. 1980, 1982; Spreafico et al. 1980). More information on the toxicokinetics of 

1,2-dichloroethane in other animal species would be useful for more fully assessing interspecies 

differences and the implications for human exposure. 

Methods of Reducing Toxic Effects. A data need has been identified. It appears that 

1,2-dichloroethane is absorbed across the alveolar membrane, gastrointestinal epithelium, and skin by 

passive means. Methods to reduce absorption following oral and dermal exposure are available, but must 

be applied soon after exposure (Ellenhorn and Barceloux 1988). The available data suggest that 

1,2-dichloroethane does not accumulate in the nonlipid components of the human body, but that it may 

accumulate to some extent in adipose tissue and in the breast milk of nursing women. Methods to 

enhance removal of 1,2-dichloroethane from the body have not been successful (Ellenhorn and Barceloux 

1988); determination of successful methods is needed. The mechanism of action of 1,2-dichloroethane is 

not clearly understood but involves complex toxifying and detoxifying reactions with glutathione (Jaeger 

et al. 1974; NTP 1991a). Reactive metabolites of P-450 metabolism are detoxified by conjugation with 

glutathione, but direct conjugation of unmetabolized 1,2-dichloroethane with glutathione produces 

reactive and toxic intermediates, which are in turn detoxified through additional reaction or conjugation 

with glutathione. Nevertheless, limited evidence that administration of glutathione and its precursors may 

have a protective effect against 1,2-dichloroethane toxicity in animals has been reported (Heppel et al. 

1947; Jaeger et al. 1974; Johnson 1967). Further elucidation of the toxic mechanisms might enable 

identification of methods for reducing the toxic effects. 

Endocrine Disruption. A data need to conduct additional studies on the endocrine system via dermal 

exposure has been identified. 
 

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A human study that reported increased rates of premature births in female workers and in wives of male 

workers at a Chinese synthetic fiber factory (Zhao et al. 1989) should be viewed with caution because of 

the deficient reporting of design, apparent lack of control for possible confounding environmental and 

behavioral factors, small number of subjects, and co-exposure to other chemicals. No assays of endocrine 

function are available. Some studies in animals, however, provide data regarding a lack of effect of 

1,2-dichloroethane on the histology of endocrine tissues and on reproduction. Histological examinations 

of endocrine tissues were performed in animals exposed by inhalation or oral administration with 

essentially negative results (Cheever et al. 1990; Daniel et al. 1994; Heppel et al. 1946; NCI 1978; NTP 

1991a; Spencer et al. 1951; van Esch et al. 1977). The examinations in these studies were generally 

limited to the adrenal gland and/or pancreas, although the pituitary, thyroid, and parathyroid glands were 

also evaluated following chronic inhalation and oral exposures. The only endocrine-related finding was 

calcification of the adrenal medulla in one of two monkeys exposed to 1,2-dichloroethane by inhalation in 

an intermediate-duration study (Heppel et al. 1946), but no controls were examined, and adrenal effects 

have not been reported in other long-term inhalation studies by these and other investigators. Histological 

examinations of pertinent reproductive tissues in animals in inhalation and oral studies revealed no 

changes (Cheever et al. 1990; Daniel et al. 1994; NCI 1978; NTP 1991a; van Esch et al. 1977), and 

adequately conducted studies of reproductive function in animals exposed to 1,2-dichloroethane by 

inhalation or oral routes (Alumot et al. 1976; Lane et al. 1982; Rao et al. 1980), although not definitive, 

strongly indicate that 1,2-dichloroethane is unlikely to impair reproduction at levels that are not 

maternally toxic. In an early NCI (1978) bioassay that had a number of limitations including dosage 

adjustments, possible contamination by other chemicals tested in the same laboratory, poor survival, and 

small control groups, gavage treatment with 1,2-dichloroethane in corn oil was associated with 

statistically significant increases in multiple tumor types, including mammary gland adenocarcinoma in 

female rats and mice and endometrial tumors in female mice. The finding of tumors in two endocrinesensitive tissues is suggestive. On the other hand, the mechanism of carcinogenicity for 1,2-dichloroethane appears to involve alkylation of DNA, and statistically significant increased incidences were also 

observed for tumors of the forestomach, circulatory system, subcutaneous tissue, liver, and lung in the 

NCI (1978) study. The oral and inhalation data for noncancer effects in animals do not suggest that 

1,2-dichloroethane has endocrine disrupting activity. No data are available for the dermal route, so there 

is a need for screening data (e.g., reproductive and other endocrine histopathology in a dermal study). 

Children’s Susceptibility. A data need to conduct additional studies relevant to children’s 

susceptibility via oral, inhalation, and dermal exposure has been identified. Data on the effects of 

1,2-dichloroethane exposure in children are limited to a single case report of a 14-year-old boy who 
1,2-DICHLOROETHANE 148 

3. HEALTH EFFECTS 

swallowed 15 mL of the compound (Yodaiken and Babcock 1973). The most immediate signs of toxicity 

were headache and staggering gait within 2 hours of exposure, followed soon after by lethargy and 

vomiting. During the next few days, the boy developed symptoms of toxicity, increasing in variety and 

severity, that involved several organ systems, including adverse hematological effects, pulmonary edema, 

cardiac arrest (he was resuscitated), and eventual death on the 5th day after exposure from massive hepatic 

necrosis and renal tubular necrosis. Data from this case report and from reports of adult humans who died 

following acute exposure to high levels by inhalation or ingestion are consistent with animal studies 

indicating that main targets of acute toxicity include the central nervous system, respiratory tract, 

stomach, liver, and kidneys. Considering the consistency of effects in acutely exposed humans and 

animals, and data showing that the liver and kidney are sensitive targets of lower-dose and longer-term 

inhalation and oral exposures in animals, it is reasonable to assume that effects in these tissues would also 

be seen in similarly exposed adults and children. 

Evidence from mouse studies suggests that the specific nature of oral exposure or the age of the animals 

at the time of the immune testing may play a role in the degree of immunotoxicity expressed in young 

animals. Repeated gavage administration for 14 days of 1,2-dichloroethane appears to be more effective 

in eliciting an immunotoxic response than 90-day drinking-water exposure in 5-week-old mice (Munson 

et al. 1982). While this difference could be due to the saturation of detoxifying/excretion pathways by 

bolus gavage dosing, an alternative explanation is that young mice may be more sensitive to 1,2-dichloroethane than adult mice. The mice used for both the acute (14-day) and the 90-day studies were 5 weeks 

old at the start of dosing, so at the time of testing, the mice in the 14-day study were 7 weeks old, but the 

mice in the 90-day study were 17 weeks old. The decreased immune response in mice exposed at 

5–7 weeks of age provides a limited indication of the potential susceptibility of children to immunotoxic 

effects. Because no immunotoxic effects were seen in young rats exposed to much higher inhalation 

concentrations of 1,2-dichloroethane than those that produced immunosuppression in mice (Sherwood et 

al. 1987), and because there are no reports of immune effects in humans exposed to this chemical, the 

relevance of the data in young mice to children is uncertain. Studies that also evaluate for other 

toxicological end points after exposures in immature animals are needed, particularly for known targets of 

toxicity such as the liver and kidney. Appropriate comparative studies are needed to document the 

toxicological potential and metabolism of 1,2-dichloroethane and to assess whether children and adults 

are equally susceptible, especially after longer-term exposures. 

No studies that provide reliable information on adverse developmental effects in humans exposed to 

1,2-dichloroethane are available. A cross-sectional epidemiologic study that investigated whether 
1,2-DICHLOROETHANE 149 

3. HEALTH EFFECTS 

elevated levels of routinely sampled organic contaminants in New Jersey public water systems, including 

1,2-dichloroethane, were associated with increased prevalences of adverse birth outcomes (Bove 1996; 

Bove et al. 1995) was located. A number of associations between various chemicals and birth outcomes 

were found, including a positive association between ingestion of 1,2-dichloroethane in drinking water 

and major cardiac birth defects (but not neural tube defects). Similarly, a study that investigated 

residence within the census tract of NPL sites contaminated with 1,2-dichloroethane reported an 

association with neural tube (but not heart defects) (Croen et al. 1997). The mixed chemical exposures in 

these studies, and the lack of concordance on end point, indicate that the results are only suggestive, do 

not establish a cause-and-effect relationship, and should be interpreted with caution. 

Studies in rats, mice, and rabbits indicate that 1,2-dichloroethane is not developmentally toxic following 

inhalation or oral gestational exposure, although fetolethality has been reported at maternolethal exposure 

levels following inhalation exposure (Kavlock et al. 1979; Lane et al. 1982; Payan et al. 1995; Rao et al. 

1980). Embryolethality was reported at relatively low exposure levels in another inhalation study 

(Vozovaya 1977), but the reliability of these results cannot be evaluated due to limitations in reporting 

and data analysis. 

No studies that evaluated for the distribution of 1,2-dichloroethane or its metabolites across the placenta 

in humans were located. However, there is some evidence that 1,2-dichloroethane and/or its metabolites 

crosses the placenta after inhalation and oral exposures in animals. 1,2-Dichloroethane was found in 

maternal blood (83.6±20.2 mg %), placental tissue (43.0±9.6 mg %), amniotic fluid (55.5±11.1 mg %), 

and fetal tissue (50.6±11.5 mg %) after inhalation exposure of female rats to 247±10 ppm 1,2-dichloroethane during pregnancy (Vozovaya 1977). Additional evidence of transplacental distribution of 

1,2-dichloroethane after inhalation exposure is provided by Withey and Karpinski (1985), who found that 

the geometric mean concentration of 1,2-dichloroethane in the fetuses of rats that inhaled 150–2,000 ppm 

for 5 hours increased linearly with increasing exposure level. However, the reliability of the Vozovaya 

data is unclear, and the methods for evaluating 1,2-dichloroethane tissue concentrations were not reported 

in Withey and Karpinski (1985). 

There is clearer evidence for transplacental distribution of 1,2-dichloroethane and/or its metabolites after 

maternal oral exposure. Payan et al. (1995) evaluated [14C]-1,2-dichloroethane distribution in maternal 

rats following a single oral bolus dose of approximately 160 mg/kg on gestation day 12 or 18. In both 

cases, transplacental distribution of radiocarbon was demonstrated by the presence of radioactivity in the 

developing conceptus. A greater accumulation occurred in the developing fetus and placenta 48 hours 
1,2-DICHLOROETHANE 150 

3. HEALTH EFFECTS 

after the gestation day 18 administration than after the gestation day 12 administration. At 48 hours after 

the gestation day 18 dosing, the majority of residual radioactivity burden was located in the fetus (0.167% 

of administered dose) and the liver (0.156% of administered dose). 

No studies regarding 1,2-dichloroethane metabolism in children were located. The metabolism of 

1,2-dichloroethane is well described (NTP 1991a; WHO 1995), and it is reasonable to assume that the 

metabolic pathways are, for the most part, the same between adults and children. However, the 

expression of certain enzymes is known to be developmentally regulated, and one of these enzymes may 

be involved in 1,2-dichloroethane metabolism. NAT is involved in 1,2-dichloroethane metabolism at a 

step subsequent to GSH conjugation. NAT performs the N-acetylation of S-carboxymethyl-L-cysteine to 

N-acetyl-S-carboxymethyl-L-cysteine, a major urinary metabolite. There are, however, two NATs 

(NAT1 and NAT2) that are expressed in humans with separate but overlapping substrate specificities 

(Parkinson 1996). NAT2 is apparently expressed only in the liver and the gut (Parkinson 1996), and is 

known to be developmentally regulated (Leeder and Kearns 1997). Some NAT2 activity is present in the 

fetus at 16 weeks, but NAT2 activity is low in virtually 100% of infants, not reaching adult activity levels 

until 1–3 years of age (Leeder and Kearns 1997). It is not clear in NTP (1991a) or WHO (1995) whether 

the NAT involved in 1,2-dichloroethane metabolism is NAT1 or NAT2, although both enzymes 

N-acetylate some xenobiotics equally well (Parkinson 1996). The impact of lower rates of N-acetylation 

of S-carboxymethyl-L-cysteine in terms of potential health effects also is unclear. 

1,2-Dichloroethane has been detected in human milk (EPA 1980a; Urusova 1953), indicating that 

developing children could possibly be exposed to 1,2-dichloroethane from breast-feeding mothers. The 

importance of this route of developmental exposure is unclear because current data on the concentration 

of 1,2-dichloroethane in breast milk are not available. 1,2-Dichloroethane was also accumulated in the 

adipose tissue of rats after inhalation exposure and was eliminated from fat more slowly than from blood, 

liver, and lung (Spreafico et al. 1980), suggesting the possibility that the maternal body burden of 

1,2-dichloroethane in fat could be available for exposure to the fetus or nursing infant for a somewhat 

extended period after maternal exposure. Supporting data for relatively slow elimination of 1,2-dichloroethane from fat are provided in an intravenous exposure study in rats (Withey and Collins 1980). 

Nevertheless, 1- and 2-generation reproductive studies of 1,2-dichloroethane, administered by inhalation 

or drinking water exposure to rats and mice, in which the pups were exposed through the milk of the 

treated dams, showed no adverse effects on survival, body weight, gross appearance of tissues and organs 

(Lane et al. 1982; Rao et al. 1980), or histological appearance of the liver, kidneys, ovaries, uterus, and 

testes (Rao et al. 1980) in the pups at 21 days of age. 
1,2-DICHLOROETHANE 151 

3. HEALTH EFFECTS 

Child health data needs relating to exposure are discussed in 6.8.1 Identification of Data Needs: 

Exposures of Children. 

3.12.3 Ongoing Studies 

The role of 1,2-dichloroethane and two other common groundwater contaminants, individually and in 

combination, in the development of hepatic angiosarcoma will be studied by Dr. Wendy A. Pott at the 

Foothills Campus of Colorado State University (FEDRIP 2000). The long-term objectives of this project 

are (1) to evaluate the carcinogenic effects of subchronic exposure to 1,2-dichloroethane, arsenic, and 

vinyl chloride, which are implicated as etiologic agents in the development of angiosarcoma; and (2) to 

use data from these studies with PBPK/PD models and statistical and mathematical modeling techniques 

for the purpose of health-risk characterization. Specific aims of the project include (1) evaluating whether 

synergistic carcinogenic activity may result when arsenic is combined with 1,2-dichloroethane; (2) 

developing PBPK/PD models for target tissue dosimetry of single chemicals and combinations of 

chemicals following exposure to arsenic, vinyl chloride, and/or 1,2-dichloroethane; and (3) developing 

cell turnover and carcinogenesis models and integrating them with PBPK/PD models to characterize 

cancer risks associated with exposure to arsenic, vinyl chloride, and/or 1,2-dichloroethane. These goals 

will be accomplished using a medium-term angiosarcoma bioassay to investigate the effects of each of the 

chemicals, alone and in combination, in inducing hepatic angiosarcoma. Data gathered from these 

experiments will be used to develop models to determine cancer risks and safe drinking-water levels of 

these chemicals. 

1,2-DICHLOROETHANE 153 

4. CHEMICAL AND PHYSICAL INFORMATION
 

4.1 CHEMICAL IDENTITY
 

The chemical formula, structure, synonyms, and identification numbers for 1,2-dichloroethane are listed 

in Table 4-1. 

4.2 PHYSICAL AND CHEMICAL PROPERTIES 

The physical and chemical properties of 1,2-dichloroethane are located in Table 4-2. 
1,2-DICHLOROETHANE 154 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-1. Chemical Identity of 1,2-Dichloroethane 

Characteristic Information Reference 

Chemical Name 1,2-Dichloroethane Budavari et al. 1996
 

Synonym(s) Ethylene dichloride; Budavari et al. 1996
 

dichloroethane; EDC;
 

Dutch liquid
 

Registered trade name(s) No data
 

Chemical formula C2H4Cl2 Budavari et al. 1996
 

Chemical structure Budavari et al. 1996
 H H 

Cl C C Cl 

H H 

Identification numbers:
 

CAS registry 107-06-2 Lide 1998
 

NIOSH RTECS KI0525000 HSDB 2001
 

EPA hazardous waste U077 HSDB 2001
 

OHM/TADS 7216717 HSDB 2001
 

DOT/UN/NA/IMCO shipping 1184 HSDB 2001
 

HSDB 65 HSDB 2001
 

NCI C00511 HSDB 2001
 

CAS = Chemical Abstracts Services; DOT/UN/NA/IMCO = Department of Transportation/United 

Nations/North America/International Maritime Dangerous Goods Code; EPA = Environmental Protection 

Agency; HSDB = Hazardous Substances Data Bank; NCI = National Cancer Institute; NIOSH = National 

Institute for Occupational Safety and Health; OHM/TADS = Oil and Hazardous Material/Technical 

Assistance Data system; RTECS = Registry of Toxic Effects of Chemical Substances 
1,2-DICHLOROETHANE 155 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of 1,2-Dichloroethane 

Property Information Reference 

Molecular weight 98.96 Lide 1998 

Color Colorless Lewis 1993 

Physical state Heavy liquid Budavari et al. 1996 

Melting point -35.5 EC Lide 1998 

Boiling point 83.5 EC Lide 1998 

Density:

 at 20 EC 1.23 g/cm3 Lide 1998 

Odor Pleasant odor Budavari et al. 1996 

Odor threshold:

 Water 20 mg/L Verschueren 1996

 Air 12 ppm Verschueren 1996 

50 ppm Torkelson and Rowe 1981 

100 ppm Weiss 1980 

Solubility:

 Water at 20 EC 8.69x103

 mg/L Verschueren 1996

 Organic solvent(s) Miscible with alcohol, Budavari et al. 1996 

chloroform and ether 

Partition coefficients:

 Log Kow 1.48 Hansch et al. 1995

 Log Koc 1.28 Chiou et al. 1980 

1.52 Sabljic et al. 1995 

1.62 Borisover and Graber 1997 

Vapor pressure 79.1 mmHg at 25 EC Daubert et al. 1989 

Henry’s law constant 1.1x10-3atm-m3

/mol Staudinger and Roberts 1996 

at 20 EC 

Autoignition temperature 413 EC Weiss 1980 
1,2-DICHLOROETHANE 156 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of 1,2-Dichloroethane (continued) 

Property Information Reference 

Flashpoint 13 EC (closed cup) 

18 EC (open cup) 

Budavari et al. 1996 

Budavari et al. 1996 

Conversion factors:

 ppm (v/v) to mg/m3

 in air (25 EC) 

ppm(v/v)x4.05 = mg/m3 Torkelson 1994

 mg/m3 to ppm (v/v)

 in air (25 EC) 

mg/m3x0.247 = ppm(v/v) Torkelson 1994 

Explosive limits 6-16% v/v in air Lewis 1993 
1,2-DICHLOROETHANE 157 

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

5.1 PRODUCTION 

1,2-Dichloroethane does not occur naturally (IARC 1979). It is produced commercially either by direct 

chlorination or by oxychlorination. Direct chlorination is carried out in the liquid or vapor phase over 

iron, aluminum, copper, or antimony chloride catalysts at 60 EC. Oxychlorination is carried out in a fixed 

or fluidized bed reactor at 220 EC with a suitable solid chloride catalyst (Sundaram et al. 1994). 

Currently, there are 12 domestic manufacturers of 1,2-dichloroethane; production occurs at 16 sites 

located predominantly in Texas, Kentucky, and Louisiana (Anonymous 1998; SRI 1998). Domestic 

producers and their annual capacities as of February 16, 1998 are listed in Table 5-1 (Anonymous 1998). 

U.S. production totals for 1,2-dichloroethane in 1984, 1985, 1986, 1990, 1992, 1993, and 1994 were 7.3, 

12.1, 12.9, 13.8, 15.2, 17.9, and 16.8 billion pounds, respectively (USITC 1985, 1986, 1987, 1991, 1993, 

1994, 1995). In 1986, sales were nearly 800 million pounds and were valued at .66 million dollars 

(USITC 1987). By 1994, sales had reached 2.8 billion pounds and were valued at .317 million dollars 

(USITC 1995). Sales of 1,2-dichloroethane on the open market in 1986 were .6% of the total 

1,2-dichloroethane produced (USITC 1987), indicating that the producers captively consumed >90% of 

production (EPA 1985a). Currently, .85% of total production is used captively (USITC 1995). 

According to the Toxics Release Inventory (TRI), 41 facilities manufactured or processed 

1,2-dichloroethane in 1999 (TRI99 2001). All of these facilities reported the range of the maximum 

amounts of 1,2-dichloroethane that they have on site. A summary of these data are presented in 

Table 5-2. The data listed in the TRI should be used with caution since only certain types of facilities are 

required to report. This is not an exhaustive list. 

5.2 IMPORT/EXPORT 

In 1996, 2.5 billion pounds of 1,2-dichloroethane were exported while 316 million pounds were imported 

to the United States (Anonymous 1998). This trend in import/export volume was also observed from 

1992 to 1996 when the average amount of 1,2-dichloroethane exported was 2.1 billion pounds annually 

and the average amount imported was 267 million pounds annually (Anonymous 1998). 
1,2-DICHLOROETHANE 158 

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

Table 5-1. United States Production of 1,2-Dichloroethanea,b 

Annual capacity 

Manufacturer Location (millions of pounds) 

Borden Chemicals and Plastics Geismar, Louisiana 745 

CONDEA Vista Company Lake Charles, Louisiana 1,400 

Dow Chemical U.S.A. Freeport, Texas 4,500 

Plaquemine, Louisiana 2,300 

Formosa Plastics Corporation U.S.A. Baton Rouge, Louisiana 525 

Point Comfort, Texas 1,900 

Geon Company LaPorte, Texas 4,000 

Georgia Gulf Corporation Plaquemine, Louisiana 1,760 

Occidental Chemical Corporation Convent, Louisiana 1,500 

Electrochemicals and Deer Park, Texas 1,950

Proprietary Products Division 

Electrochemicals Ingleside, Texas 1500 

Oxymar Ingleside, Texas 3,000 

PHH Monomers Lake Charles, Louisiana 1,400 

PPG Industries, Inc. Lake Charles, Louisiana 1,600 

Chemicals Group 

Vulcan Materials Company Geismar, Louisiana 500 

Vulcan Chemicals Division 

Westlake Monomers Corporation Calvert City, Kentucky 1,950 

Total 30,530 

a

Derived from Anonymous 1998

b

Estimates as of February 16, 1998 
1,2-DICHLOROETHANE 159 

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

Table 5-2. Facilities that Produce, Process, or Use 1,2-Dichloroethane 

Range of maximum 

Number of amounts on site in 

Statea facilities poundsb Activities and usesc 

CA 2 100–99,999 10 

IA 1 1,000–9,999 1 

KY 3 1,000–49,999,999 1, 2, 3 

LA 11 1,000–999,999,999 1, 3, 4, 10 

MI 3 1,000–99,999 1, 8 

MO 3 100–9,999,999 1, 3, 8 

PA 2 10,000–999,999 1 

PR 2 10,000–99,999 2, 3 

SC 1 100,000–999,999 1 

TX 13 0–999,999,999 1, 2, 3, 4, 8, 10 

Source: TRI99 2001 

a

Post office state abbreviations used 

b

Range represents maximum amounts on site reported by facilities in each state c

Activities/Uses: 

1. Produce 6. Impurity 10. Repackaging 

2. Import 

3. Onsite use/processing 

7. Reactant 

8. Formulation Component 

11. Chemical Processing Aid 

12. Manufacturing Aid 

4. Sale/Distribution 

5. Byproduct 

9. Article Component 13. Ancillary/Other Uses 
1,2-DICHLOROETHANE 160 

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

5.3 USE 

1,2-Dichloroethane is currently used as a chemical intermediate and as a solvent in closed systems (Dow 

Chemical Company 1989b). It is also added to leaded gasoline as a lead scavenger; however, this use has 

declined significantly as leaded gasoline use has attenuated (Vulcan Materials Company 1989). In the 

United States, about 98% of the 1,2-dichloroethane produced is used to manufacture vinyl chloride 

(Anonymous 1998). Smaller amounts of 1,2-dichloroethane are used in the synthesis of vinylidene 

chloride, 1,1,1-trichloroethane, trichloroethene, tetrachloroethene, aziridines, and ethylene diamines and 

in chlorinated solvents (Anonymous 1998; EPA 1985a). 

Formerly, 1,2-dichloroethane was used in varnish and finish removers, in soaps and scouring compounds, 

in organic synthesis for extraction and cleaning purposes, in metal degreasers, in ore flotation, and in 

paints, coatings, and adhesives (Archer 1979; Budavari et al. 1996; Dow Chemical Company 1989b; EPA 

1985a). It was also formerly used as a grain, household, and soil fumigant (Archer 1979; CMA 1989; 

Dow Chemical Company 1989b; EPA 1985a; Vulcan Materials Company 1989). 

5.4 DISPOSAL 

1,2-Dichloroethane can be removed from water by treatment with granulated activated carbon, by 

aeration (air stripping), and by boiling. One of the main drawbacks of granulated activated carbon 

removal is that the spent carbon must be further processed by desorbing the chemical with steam or 

thermal carbon regeneration and concomitant incineration of the desorbed chemicals. Recently, 

granulated active carbon treatment has been combined with bioremediation technologies to increase the 

removal capacity of 1,2-dichloroethane from groundwater (Stucki and Thuer 1994). Boiling is an 

effective treatment on a short-term emergency basis when low concentrations are spilled in water. Air 

stripping removes 1,2-dichloroethane simply and inexpensively from water. However, these processes 

should be used with caution, as they result in the transfer of the contaminant directly to air (EPA 1985a, 

1987d). 
1,2-DICHLOROETHANE 161 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.1 OVERVIEW 

1,2-Dichloroethane’s production, storage, and use as a synthetic feedstock (Anonymous 1998; EPA 

1985a), as a lead scavenger in leaded gasoline, and as a solvent in closed systems (Dow Chemical 

Company 1989b) may result in its release to the environment. The use of 1,2-dichloroethane as a lead 

scavenger has decreased significantly in recent years as leaded gasoline use has declined. The largest 

environmental releases of 1,2-dichloroethane occur to air. 1,2-Dichloroethane released to surface water 

and soil is expected to volatilize rapidly to the atmosphere where it will be degraded by photochemicallyproduced hydroxyl radicals. The half-life for this reaction is about 73 days, calculated from its measured 

rate constant (Arnts et al. 1989; Atkinson et al. 1989), and the overall atmospheric lifetime of 

1,2-dichloroethane is >5 months (EPA 1993). Hydrolysis and photolysis do not appear to be significant 

in determining the environmental fate of 1,2-dichloroethane. Although biodegradation occurs slowly, it is 

the primary degradation process for 1,2-dichloroethane in soils and waters. 1,2-Dichloroethane has been 

detected in ambient air, surface water, groundwater, drinking water, human breath, urine, and milk 

samples. Concentrations in environmental media are generally greatest near source areas (e.g., industrial 

point sources, hazardous waste sites). 

1,2-Dichloroethane has been identified in at least 570 of the 1,585 hazardous waste sites that have been 

proposed for inclusion on the EPA National Priorities List (NPL) (HazDat 2001). However, the number 

of sites evaluated for 1,2-dichloroethane is not known. The frequency of these sites can be seen in 

Figure 6-1. Of these sites, 569 are located within the United States and 1 is located in the Commonwealth 

of Puerto Rico (not shown). 

Inhalation of 1,2-dichloroethane in ambient or workplace air is generally the main route of human 

exposure to the compound. Estimates of populations potentially exposed to 1,2-dichloroethane in 

workplace environments range from 80,000 to 1.4 million workers (NIOSH 1976a, 1984a). The 

estimated size of the general population potentially exposed to low levels of the compound through 

inhalation of polluted ambient air around industrial sites was .15 million people (Kellam and Dusetzina 

1980). Ingestion of contaminated drinking water and food may also be important routes of exposure. 
Figure 6-1. Frequency of NPL Sites with 1,2-Dichloroethane Contamination 

1-5 6-114-22-39-63 

Frequency of

NPL Sites 

Derived from HazDat 2001 
1,2-DICHLOROETHANE 163 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.2 RELEASES TO THE ENVIRONMENT 

There are no known natural sources of 1,2-dichloroethane. Releases of this compound to the environment 

may result from the manufacture, use, storage, distribution, and disposal of 1,2-dichloroethane. Older 

consumer goods containing 1,2-dichloroethane that are still in use or have been discarded as waste also 

represent potential emission sources. 1,2-Dichloroethane may also be released to the environment from 

the microbial degradation of other chlorinated alkanes. For example, 1,2-dichloroethane is a known 

product of the anaerobic biodegradation of 1,1,2,2-tetrachloroethane (Chen et al. 1996; Lorah and Olsen 

1999). 

6.2.1 Air 

Emissions to the atmosphere comprise the largest component of all releases of 1,2-dichloroethane to the 

environment. According to the Toxics Release Inventory (TRI) (Table 6-1), an estimated total of 

546,039 pounds of 1,2-dichloroethane, amounting to 88.8% of the total on-site environmental release, 

was discharged to air from manufacturing and processing facilities in the United States in 1999 

(TRI99 2001). The TRI data should be used with caution because only certain types of facilities are 

required to report. This is not an exhaustive list. 

1,2-Dichloroethane has been identified in air samples collected at 39 of the 570 NPL hazardous waste 

sites where it was detected in some environmental media (HazDat 2001). 

6.2.2 Water 

Industrial releases of 1,2-dichloroethane to surface waters are relatively minor compared to releases to the 

atmosphere. According to the TRI (Table 6-1), an estimated total of 904 pounds of 1,2-dichloroethane, 

amounting to 0.1% of the total on-site environmental release, was discharged to water from 

manufacturing and processing facilities in the United States in 1999 (TRI99 2001). The TRI data should 

be used with caution because only certain types of facilities are required to report. This is not an 

exhaustive list. 

In England and Wales, 1,2-dichloroethane was detected in 17% of industrial waste water effluent samples 

at an average concentration of 117 μg/L, and in 9.5% of treated sewage at an average concentration of 

1.39 μg/L (Stangroom et al. 1998). 1,2-Dichloroethane has been identified in surface water samples 
Table 6-1. Releases to the Environment from Facilities that Produce, Process, or Use 1,2-D

Stateb 

Number of facilities Airc 

Reported amounts released in pounds per yeara 

Water 

Underground injection Land 

Total on-site released 

Total off-sitreleas

AL 2 18 No data No data No data 18 10,453 

AR 4 10,143 70 0 0 10,213 150,5CA 2 264 No data No data No data 264 83 

GA 1 No data No data No data No data No data No da

IA 2 307 No data No data No data 307 No da

IL 4 20,529 No data No data 0 20,529 147 IN 2 26,070 5 No data 5 26,080 No da

KS 1 3,549 38 No data No data 3,587 No da

KY 3 21,557 47 No data 0 21,604 255 

LA 19 222,595 343 51,116 2,972 277,026 2,472 

MA 1 1,178 No data No data No data 1,178 No da

MI 3 162 No data No data No data 162 No daMO 3 28,815 25 No data 5 28,845 No da

MS 1 7,420 No data 1,040 No data 8,460 No da

NC 2 5,466 1 No data No data 5,467 952 
Table 6-1. Releases to the Environment from Facilities that Produce, Process, or Use 1,2-D

(continued) 

Reported amounts released in pounds per yeara 

Total 

Stateb 

Number of 

facilities Airc Water 

Underground injection Land 

Total on-site released 

site releas

NE 1 255 No data No data 0 255 No da

NJ 1 18 0 No data 0 18 2 

NY 2 524 255 No data No data 779 72,446 

OH 3 86 1 No data No data 87 49 

PA 6 25,244 No data No data No data 25,244 No da

PR 3 470 No data No data No data 470 No da

SC 2 27,661 No data No data No data 27,661 0 

TX 18 143,703 119 13,309 1 157,132 445,87

VA 1 5 No data No data No data 5 No da

WI 1 No data No data No data No data No data No da

Total 89 546,039 904 65,465 2,983 615,391 683,30

Source: TRI99 2001 aData in TRI are maximum amounts released by each facility.bPost office state abbreviations are used.cThe sum of fugitive and stack releases are included in releases to air by a given facility. dThe sum of all releases of the chemical to air, land, water, and underground injection wells. eTotal amount of chemical transferred off-site, including to publicly owned treatment works (POTW).
1,2-DICHLOROETHANE 166 

6. POTENTIAL FOR HUMAN EXPOSURE 

collected at 89 sites and groundwater samples collected at 492 of the 570 NPL hazardous waste sites 

where it was detected in some environmental media (HazDat 2001). 

6.2.3 Soil 

Industrial releases of 1,2-dichloroethane to soil are relatively minor compared to releases to the 

atmosphere. According to the TRI (Table 6-1), an estimated total of 2,983 pounds of 1,2-dichloroethane, 

amounting to 0.5% of the total on-site environmental release, was discharged to land from manufacturing 

and processing facilities in the United States in 1999 (TRI99 2001). An additional 65,465 pounds of 

1,2-dichloroethane, amounting to 10.6% of the total on-site environmental release, was injected 

underground. The TRI data should be used with caution because only certain types of facilities are 

required to report. This is not an exhaustive list. 

1,2-Dichloroethane has been identified in soil samples at 166 sites and sediment samples at 42 of the 

570 NPL hazardous waste sites where it was detected in some environmental media (HazDat 2001). 

6.3 ENVIRONMENTAL FATE 

1,2-Dichloroethane released to the environment partitions to the atmosphere. Reaction with 

photochemically produced hydroxyl radicals is the primary degradation mechanism of 1,2-dichloroethane 

in the atmosphere. 1,2-Dichloroethane released to soil or water surfaces is expected to volatilize quickly. 

Biodegradation occurs slowly in water and soil surfaces. Hydrolysis and photolysis are not expected to 

be important environmental fate processes for 1,2-dichloroethane. 

6.3.1 Transport and Partitioning 

Releases of 1,2-dichloroethane to the environment as a result of industrial activity are primarily to the 

atmosphere (see Section 6.2). 1,2-Dichloroethane released to the atmosphere may be transported long 

distances before being washed out in precipitation or degraded. For example, Pearson and McConnell 

(1975) attributed the presence of chlorinated organic compounds, including 1,2-dichloroethane, in upland 

waters to long-range aerial transport and deposition in precipitation. 

Based on a Henry’s law constant of 1.1x10-3 atm-m3

/mol at 20 EC (Staudinger and Roberts 1996), 

1,2-dichloroethane is expected to volatilize rapidly from water surfaces. An estimated volatilization 
1,2-DICHLOROETHANE 167 

6. POTENTIAL FOR HUMAN EXPOSURE 

half-life of 28–29 minutes was reported for 1,2-dichloroethane present at a concentration of 1 mg/L in an 

open water column held at 25 EC and stirred at 200 revolutions per minute (Dilling 1977; Dilling et al. 

1975). Removal of 90% of the compound under the same conditions occurred in 96 minutes. However, 

an evaporation half-life of 10 days was estimated using the EXAMS model for a eutrophic lake. 

Volatilization losses were shown to be the dominant fate process following a chemical spill in the Rhine 

River in Germany (Brüeggemann et al. 1991). 

No information was found regarding partitioning of 1,2-dichloroethane from the water column onto 

sediments. However, structural analogs of the compound (i.e., dichloromethane, trichloromethane, and 

1,1,1-trichloroethane) do not concentrate selectively onto sediments (Dilling et al. 1975; Pearson and 

McConnell 1975). Based on log Koc values of 1.28–1.62 (Borisover and Graber 1997; Chiou et al. 1980; 

Sabljic et al. 1995), 1,2-dichloroethane is not expected to adsorb to suspended solids and sediment in the 

water column. An experimental bioconcentration factor of 2 indicates that 1,2-dichloroethane will not 

bioconcentrate in fish and aquatic organisms (Banerjee and Baughman 1991) and is not expected to 

bioaccumulate in the food chain (Farrington 1991). 

1,2-Dichloroethane released to land surfaces is expected to volatilize rapidly to the atmosphere or leach 

into groundwater. Volatilization losses occur at a much slower rate for 1,2-dichloroethane present in subsurface soil. Jury et al. (1990) modeled the rate of volatilization of 1,2-dichloroethane from soil at a 

depth of 1 m to mimic the type of contamination that may occur from landfill leachate. When water 

evaporation was not taken into account, the yearly loss of 1,2-dichloroethane amounted to 7.1% from a 

sandy soil. Yearly volatilization losses increased to 30% when water evaporation was considered. Based 

on log Koc values of 1.28–1.62 (Borisover and Graber 1997; Chiou et al. 1980; Sabljic et al. 1995), 

1,2-dichloroethane is expected to have very high mobility in soil surfaces and should be available for 

transport into groundwater. In a laboratory experiment conducted with a sandy loam, approximately 50% 

of an initial concentration of 0.81 mg/L of 1,2-dichloroethane applied to the soil surface was volatilized. 

The remainder percolated through the soil column to a depth of 140 cm, suggesting that leaching into 

groundwater may occur (Wilson et al. 1981). Environmental surveys conducted by EPA have detected 

1,2-dichloroethane in groundwater sources in the vicinity of contaminated sites (EPA 1985a). Large 

spills of 1,2-dichloroethane may contaminate groundwater because of the high density of this compound, 

which makes it sink into the aquifer in a vertical gravity-driven process (Corapcioglu and Hossain 1990). 
1,2-DICHLOROETHANE 168 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.3.2 Transformation and Degradation 

6.3.2.1 Air 

In the atmosphere, 1,2-dichloroethane is degraded by reaction with photochemically produced hydroxyl 

radicals. An experimental rate constant of 2.2x10-13 cm3

/molecule-second at 25 EC (Arnts et al. 1989; 

Atkinson et al. 1989) corresponds to a half-life of 73 days using an average atmospheric hydroxyl radical 

concentration of 5x105

 molecule/cm3. The estimated atmospheric lifetime of 1,2-dichloroethane was 

reported to be >5 months with formyl chloride, chloroacetyl chloride, hydrogen chloride, and 

chloroethanol reported as degradation products (EPA 1993). 1,2-Dichloroethane is not expected to 

undergo significant atmospheric removal by oxidation with ozone or nitrate radicals, and it will not 

undergo removal by direct photolysis. 

6.3.2.2 Water 

In groundwater and surface water, biodegradation is the primary degradation process for the removal of 

1,2-dichloroethane. Abiotic degradation processes, such as oxidation and hydrolysis, are too slow to be 

environmentally significant. 

Bacteria isolated from a mixture of activated sludge from waste water treatment plants and 1,2-dichloroethane-polluted soils have used 1,2-dichloroethane as a sole carbon source (Janssen et al. 1984; Stucki 

et al. 1983). Approximately 14% degradation of 5 mg/L 1,2-dichloroethane occurred after 14 days 

incubation in laboratory experiments using a domestic waste water inoculum (Tabak et al. 1981). The 

reported loss was corrected for 27% volatilization loss in 10 days from control flasks. Reported 

degradation losses (corrected for volatilization) for 10 mg/L of the compound were 15% at 7 days and 

30% at 14 days. Following a 24-hour incubation at 25 EC under aerobic conditions, 1,2-dichloroethane 

was degraded (approximately 10%) by a strain of Pseudomonas fluorescens bacteria isolated from soil 

and water contaminated with various chlorinated hydrocarbons, including 1,2-dichloroethane 

(Vandenbergh and Kunka 1988). 1,2-Dichloroethane was not biodegraded after 35 days under anaerobic 

conditions in sediment-water test systems (Jafvert and Wolfe 1987) and was not biodegraded by bacteria 

isolated from groundwater after 8–16 weeks incubation (Wilson et al. 1983). However, recent reviews 

indicate that the biodegradation of 1,2-dichloroethane to ethene in anaerobic waters is a probable fate 

process (Kuhn and Suflita 1989; Saint-Fort 1991). The biodegradation half-life of 1,2-dichloroethane in 

aerobic water was reported as 100 days and the half-life in anaerobic water was reported as 400 days, but 
1,2-DICHLOROETHANE 169 

6. POTENTIAL FOR HUMAN EXPOSURE 

no details on the kinetic experiments used to establish these half-lives were reported (Capel and Larson 

1995). The half-life represents the calculated time for loss of the first 50% of the substance, but the time 

required for the loss of half of that which remains may be substantially longer, and the rate of 

disappearance may decline further as time progresses. 1,2-Dichloroethane was 97% biodegraded in 

laboratory studies using aerobic groundwater microcosms obtained from a Superfund site in California 

over a 6-day incubation period (Cox et al. 1998). In the field, however, the biodegradation half-life of 

1,2-dichloroethane in groundwater can range from less than a year to 30 years depending on the 

conditions (Bosma et al. 1998). 

A growing body of evidence indicates that the co-metabolism of 1,2-dichloroethane (the biodegradation 

of 1,2-dichloroethane from which the degrading organism gains no energetic benefit) occurs under 

aerobic conditions (see Section 6.3.2.3). Pure cultures of methanotrophic (methane using) bacteria 

obtained from both polluted and nonpolluted sources degraded 1,2-dichloroethane in the presence of 

methane and oxygen (Oldenhuis et al. 1989). Aquifer solids obtained at an in situ biorestoration field 

study mineralized 1,2-dichloroethane to carbon dioxide in the presence of dissolved oxygen and methane 

(Lanzarone and McCarty 1990). Concentrated cell suspensions of methanogenic bacteria incubated at 

37 or 55 EC for 24–96 hours reductively dechlorinated 1,2-dichloroethane to ethene, chloroethane, and 

ethane (Holliger et al. 1990). 

The experimental first-order rate constants for the hydrolysis of 1,2-dichloroethane under neutral 

conditions were reported as 2.1x10-8 second-1 and 1.8x10-8 second-1 at 25 EC (Barbash and Reinhard 1989; 

Jeffers et al. 1989). These values correspond to half-lives of 65 and 72 years. A more recent study 

determined that the hydrolysis half-life of 1,2-dichloroethane was 4.9x104

 years at pH 9 and 15 EC 

(Miyamoto and Urano 1996). Barbash and Reinhard (1989) found that the presence of 5.1x10-4 molar 

(16 ppm) solution of hydrogen sulfide anion decreased the hydrolytic half-life to 6 years. Although still a 

slow process, this latter reaction may occur in hypoxic groundwater where hydrogen sulfide occurs 

naturally. 

6.3.2.3 Sediment and Soil 

As in surface water, direct photolysis of 1,2-dichloroethane on soil surfaces and hydrolysis in moist soil 

and sediment are not expected to be important environmental fate processes. The primary transformation 

process for 1,2-dichloroethane in sediment and soil is biodegradation. 
1,2-DICHLOROETHANE 170 

6. POTENTIAL FOR HUMAN EXPOSURE 

Incubation of 1,2-dichloroethane at a starting concentration of 100 ppb with an unsaturated calcareous 

soil resulted in 15–23% mineralization to carbon dioxide after 4 weeks, under aerobic conditions, and 

3.3–3.4% mineralization under anaerobic conditions (Watwood et al. 1991). 1,2-Dichloroethane (2 μmol) 

was completely dechlorinated to ethane by anaerobic microcosms and enrichment cultures derived from 

river sediment over a 2-week incubation period (Loffler et al. 1997). A first-order biodegradation rate 

constant of 0.013 day-1 was determined for 1,2-dichloroethane in an anaerobic sediment slurry 

(Peijnenburg et al. 1998). This rate constant corresponds to a biodegradation half-life of about 52 days. 

It was noted that degradation followed first-order kinetics for at least two successive half-lives in this 

study. 

The presence of methane or increasing the proportion of methanotrophs can increase the rate of aerobic 

biodegradation of 1,2-dichloroethane in soil. In laboratory experiments conducted with different soil 

types (sand, sandy clay, silty loam, clay, and Lincoln fine sand), soils exposed to methane biodegraded 

1,2-dichloroethane to carbon dioxide (Henson et al. 1988; Speitel and Closmann 1991). Based on these 

results, it was estimated that the bioremediation of soil contaminated with 100 ppm 1,2-dichloroethane 

could be complete within several months if methane is present (Speitel and Closmann 1991). Methane 

oxidizing cultures from soil of a California landfill readily biodegraded 1,2-dichloroethane, but toluene 

and phenol oxidizing cultures were not able to degrade this compound (Chang and Alvarez-Cohen 1995). 

As the concentration of 1,2-dichloroethane increases in a soil surface, the degree of biodegradation that 

takes place may decrease due to microbial toxicity at the enhanced contaminant level. In a respirometer 

study of microbial toxicity to an agricultural soil, it was determined that a concentration of 0.51 mg of 

1,2-dichloroethane per gram of soil resulted in a 50% respiratory inhibition (Regno et al. 1998). 

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT 

1,2-Dichloroethane has been detected at low levels (ppb) in ambient urban and rural air, in indoor air 

samples of residences located near hazardous waste disposal sites, and in surface water, groundwater, and 

drinking water. Quantitative concentration information is presented in the following sections. 

6.4.1 Air 

1,2-Dichloroethane has been detected in ambient air samples taken over the north Atlantic Ocean at 

concentrations of 0.061–0.12 μg/m3

 (0.015–0.030 ppb) (Class and Ballschmiter 1986) and in trace 
1,2-DICHLOROETHANE 171 

6. POTENTIAL FOR HUMAN EXPOSURE 

amounts in the southern Black Forest in southwestern Germany (concentration unspecified) (Juttner 

1986). The reported average surface level background concentration of the compound in ambient air at 

mid-latitudes is 0.168 μg/m3

 (Singh et al. 1982). 

1,2-Dichloroethane has been found at higher concentrations in ambient air samples from urban areas of 

the United States. In a review of .950 potential papers on volatile organic compounds (VOCs) in air 

published from 1970 to 1987, a database of median daily atmospheric concentrations by site type was 

compiled (EPA 1988b). The median daily atmospheric concentration of 1,2-dichloroethane in urban sites 

was 0.049 μg/m3

 (0.012 ppb) (1,214 samples) and 1.0 μg/m3 (0.26 ppb) (182 samples) for sourcedominated samples; it was not detected in 648 samples from suburban, rural, or remote sites. 

1,2-Dichloroethane was detected at 83 urban locations across the United States at a median concentration 

of 0.04 μg/m3

 (0.01 ppb) (Kelly et al. 1994). The average concentration of 1,2-dichloroethane in seven 

urban locations in 1980–1981 ranged from 0.405 to 6.07 μg/m3

 (0.100 to 1.50 ppb) (Singh et al. 1982). 

The mean concentrations of 1,2-dichloroethane in 1,412 samples of ambient air from 23 sites in 

12 Canadian cities from 1988–1990 ranged from 0.070 to 0.28 μg/m3

 (0.017 to 0.069 ppb) with an overall 

mean of 0.13 μg/m3

 (0.032 ppb) (WHO 1995). Mean urban air concentrations of 1,2-dichloroethane 

measured during field experiments in March 1984 in Downey, California, Houston, Texas, and Denver, 

Colorado were 0.40 μg/m3

 (0.010 ppb), 1.82 μg/m3 (0.45 ppb), and 0.089 μg/m3 (0.022 ppb), respectively 

(Singh et al. 1992). In a 1987 survey of 35 homes in the Kanawha Valley, West Virginia, the mean 

concentration of 1,2-dichloroethane was 20.8 μg/m3

 (5.15 ppb) with a maximum concentration of 

140 μg/m3

 (34.6 ppb) (Cohen et al. 1989). A component of the Total Exposure Assessment Methodology 

(TEAM) compared the outdoor concentration of toxic substances to the corresponding overnight indoor 

concentration. The results of this monitoring study indicated that 1,2-dichloroethane was detected in 30% 

of the indoor samples (median concentration: 0.025 μg/m3

) and 37% of the outdoor samples (median 

concentration: 0.025 μg/m3

) in Greensboro, North Carolina (fall, 1980); 89% of the indoor samples 

(3.6 μg/m3

) and 100% of the outdoor samples (2.2 μg/m3) in Baton Rouge, Louisiana (winter, 1981); 18% 

of the indoor (0.04 μg/m3

) and 40% of the outdoor samples (0.045 μg/m3) in Houston, Texas (summer, 

1981); 64% of the indoor (0.22 μg/m3

) and 54% of the outdoor samples (0.21 μg/m3) in Los Angeles, 

California (winter, 1984); 4.3% of the indoor samples (0.03 μg/m3

) and none of the outdoor samples in 

Los Angeles, California (summer, 1984); 20% of the indoor (0.12 μg/m3

) and none of the outdoor 

samples in Antioch/Pittsburgh, California (summer, 1984) (Pellizzari et al. 1986). 1,2-Dichloroethane 

was detected in only 1 of the 349 samples drawn from 11 cities in the 1990 Urban Air Toxics Monitoring 

Program (UATMP) at a concentration of 0.32 μg/m3

 (0.080 ppb) (EPA 1991c). In a survey of homes in 

North Carolina, 1,2-dichloroethane was detected at a concentration of 0.40 μg/m3

 (0.10 ppb) in 1 out of 
1,2-DICHLOROETHANE 172 

6. POTENTIAL FOR HUMAN EXPOSURE 

25 homes of smokers and was not detected in the homes of nonsmokers (Heavner et al. 1995). In a 

survey of New Jersey and Pennsylvania residences, 1,2-dichloroethane was detected in the homes of 

nonsmokers at a mean concentration of 0.03 μg/m3

 (0.007 ppb) and in the homes of smokers at a mean 

concentration of 0.32 μg/m3

 (0.079 ppb) (Heavner et al. 1996). The maximum concentration of 

1,2-dichloroethane reported in nonsmoking households was 0.54 μg/m3 (0.13 ppb), while the maximum 

concentration in households where at least one family member smoked was 9.72 μg/m3

 (2.40 ppb). 

1,2-Dichloroethane has also been detected in samples of ambient air collected in the vicinity of hazardous 

waste disposal sites. Trace amounts of 1,2-dichloroethane were found in samples of outdoor ambient air 

from two of nine residences in the Love Canal area of Niagara, New York (Barkley et al. 1980). It was 

also detected in indoor ambient air samples from two of the nine residences surveyed, at concentrations of 

0.10 μg/m3

 (0.025 ppb) and 0.13 μg/m3 (0.032 ppb). In addition, it has been found in ambient air samples 

from three of five hazardous waste sites surveyed in New Jersey at average concentrations of 0.04, 1.1, 

and 0.12 μg/m3

 (0.01, 0.28, and 0.030 ppb) (LaRegina et al. 1986). Another possible source of indoor air 

pollution is through volatilization from contaminated potable water in domestic shower and bath systems 

(Andelman 1985). 1,2-Dichloroethane was detected at concentrations of 146 μg/m3

 (36 ppb) and 

81 μg/m3

 (20 ppb) in the ambient air at municipal landfill sites in Canada (Brosseau and Heitz 1994). 

1,2-Dichloroethane was detected in 11.4% of the vented air samples obtained from the Fresh Kills landfill 

in New York at an average concentration of 0.77 mg/m3

 (0.19 ppm) (EPA 1996). 

6.4.2 Water 

In a survey of 14 heavily industrialized river basins in the United States, 1,2-dichloroethane was detected 

at a frequency of 53% in 204 surface water samples collected (EPA 1977a); reported concentrations in 

domestic surface waters used as drinking water sources ranged from trace amounts to 4.8 μg/L (Brown 

et al. 1984). 1,2-Dichloroethane has also been found in samples of urban runoff from Eugene, Oregon, at 

a concentration of 4 μg/L (Cole et al. 1984). 1,2-Dichloroethane was detected in 26% of the river 

samples obtained from Osaka, Japan, at a mean concentration of 0.09 μg/L (Yamamoto et al. 1997). 

1,2-Dichloroethane was detected in the Tees estuary in England in 1992 at concentrations of 

0.72–4.02 μg/L, with the highest levels measured near an industrialized area where 1,2-dichloroethane 

and vinyl chloride monomer were produced (Dawes and Waldock 1994). 

Groundwater samples taken from 178 hazardous waste disposal sites contained 1,2-dichloroethane at 

29.1% frequency (Plumb 1987). 1,2-Dichloroethane was detected in the groundwater of the Du Pont 
1,2-DICHLOROETHANE 173 

6. POTENTIAL FOR HUMAN EXPOSURE 

Necco Park Landfill in Niagara Falls, New York at concentrations of 14–4,250 μg/L (Lee et al. 1995). 

Reported concentrations of 1,2-dichloroethane in domestic groundwater supplies used for drinking water 

ranged from trace amounts to 400 μg/L (Brown et al. 1984). 1,2-Dichloroethane was detected in 10 of 

943 groundwater samples across the United States at concentrations that ranged from 0.95 to 9.80 μg/L 

with median concentrations ranging from 0.57 to 2.9 μg/L (Westrick et al. 1984). The disposal of organic 

chemicals in trenches at a waste disposal site near Ottawa, Canada resulted in 1,2-dichloroethane 

groundwater concentrations ranging from 3.9 to 58.0 μg/L in 30% of samples taken from a 37-well 

monitoring network in 1988 (Lesage et al. 1990). The concentration of 1,2-dichloroethane in the leachate 

samples from hazardous waste landfills in Germany ranged from 40 to 830 μg/L (Först et al. 1989). 

1,2-Dichloroethane was identified, not quantified, in groundwater wells of Eau Claire, Wisconsin (Canter 

and Sabatini 1994). 1,2-Dichloroethane was detected in 17% of groundwater samples obtained from 

479 waste disposal sites in the United States (Barbee 1994). 1,2-Dichloroethane was detected in 27 of 

82 samples of groundwater at the Darling Hill Dump, Vermont at an average concentration of 3.7 μg/L 

and a maximum concentration of 240 μg/L (EPA 1992a). The maximum concentration of 1,2-dichloroethane in groundwater at the Fallon Naval Air Station, Fallon, Nevada was 1,400 μg/L (Kelley et al. 

1998). Groundwater from a former petro-chemical refinery in California contained 1,2-dichloroethane at 

concentrations ranging from 1 to 9 μg/L (EPA 1992b). 1,2-Dichloroethane was detected at 

concentrations of 0.8–32.8 μg/L in groundwater near the Lower Llobregat aquifer in Spain (Ventura et al. 

1997). 

1,2-Dichloroethane was found in drinking water samples from a number of urban and rural locations in 

the United States. This compound has been detected in drinking water samples from New Orleans, 

Miami, Philadelphia, and Cincinnati (Clark et al. 1986; Suffet et al. 1980). Private drinking water wells 

in Wisconsin contained >7 μg/L 1,2-dichloroethane in 2 of 7 wells surveyed (Krill and Sonzogni 1986); 

in Iowa, 3 public well water supplies contained concentrations of 4–19 μg/L (EPA 1985g), and in Kansas, 

1 of 103 farmstead wells contained 1,2-dichloroethane at an average concentration of 1.25 μg/L during 

1985–1986 (Steichen et al. 1988). 1,2-Dichloroethane was detected at concentrations of 1–64 μg/L in 

56 private drinking water wells in Rhode Island (Rhode Island Department of Health 1989). It was also 

detected at 0.050 μg/L in drinking water samples from three of nine residences surveyed in the Love 

Canal area of Niagara, New York (Barkley et al. 1980). 1,2-Dichloroethane was detected in 0.5% of the 

drinking water wells studied between 1984 and 1990 in California at a maximum concentration of 

24 μg/L (Lam et al. 1994b). 
1,2-DICHLOROETHANE 174 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.4.3 Sediment and Soil 

The concentration of 1,2-dichloroethane in sediment samples obtained from the Southampton Water 

estuary, England over an 18-month period ranged from 0.070 to 11 ppb (Bianchi et al. 1991). 

1,2-Dichloroethane was not detected in sediment downstream from two facilities in Canada that 

manufactured this compound (Oliver and Pugsley 1986). The mean concentration of 1,2-dichloroethane 

in soil near 20 homes in the Netherlands was 11 mg/kg, while samples in the vicinity of a garage and 

waste site contained <5 and 30 mg/kg, respectively (WHO 1995). 1,2-Dichloroethane was detected in 

soil from Claire, Michigan near seven industrial facilities at concentrations of 6–19 μg/kg (EPA 1992c). 

6.4.4 Other Environmental Media 

In a market basket survey of over 500 samples of table-ready and prepared foods (including cereals, 

oils/dressings, vegetables, baked goods, nuts, dairy products, jams/candy, meats/meat dishes, fruits, 

infant/toddler blends, and beverages), 1,2-dichloroethane was detected in a whiskey sample at a 

concentration of 30 ng/g (Daft 1988, 1989, 1991). 1,2-Dichloroethane has been detected in plain granola 

samples at 0.31 and 12 ng/g, shredded wheat cereal samples at 8.2 ng/g (Heikes 1987), wheat grain 

samples at 0–180 ng/g, and bleached flour samples at 0–6.5 ng/g (Heikes and Hopper 1986). 

1,2-Dichloroethane has also been qualitatively detected as a volatile component in chickpeas (Rembold 

et al. 1989). 

1,2-Dichloroethane was formerly used as a fumigant, but is not currently registered for use in agricultural 

products in the United States, Canada, and the United Kingdom. 1,2-Dichloroethane was not detected in 

24 samples of rice analyzed in 1992 (WHO 1995) and was not detected in an FDA survey of 234 table 

ready foods (Heikes et al. 1995). In a survey of foods from Tokyo, Japan, 1,2-dichloroethane was not 

detected in bean sprouts, colas, juice, rice, lactic beverages, plain yogurt, tofu, or ice milk (Miyahara et al. 

1995). It was detected at mean concentrations of 1.3 ng/g in butter, 0.2 ng/g (ppb) in cake, 0.03 ng/g in 

ice cream, and 0.03 ng/g in store-bought milk (Miyahara et al. 1995). 
1,2-DICHLOROETHANE 175 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE 

The greatest source of exposure to 1,2-dichloroethane for most of the U.S. population is inhalation of the 

compound in contaminated air. Other potential routes of human exposure include ingestion of 

1,2-dichloroethane in contaminated drinking water or food items and dermal absorption (EPA 1985a; 

Gold 1980). Since 1,2-dichloroethane is not currently registered for use in agricultural products in the 

United States, the potential exposure from ingesting contaminated food sources has likely decreased. 

Ingestion of drinking water contaminated with 1,2-dichloroethane is expected to be an important route of 

exposure for only 4–5% of the population (HSDB 2001). However, for populations with drinking water 

supplies containing >6 μg/L of the compound, oral and dermal routes are expected to be more important 

than inhalation (EPA 1985a). The estimated daily intake of 1,2-dichloroethane in Japan attributed to food 

ingestion is 0.004 mg/day (Miyahara et al. 1995). Since the levels of 1,2-dichloroethane in food products 

of Japan are similar to those in the United States, the daily intake value may also be similar. 

The National Occupational Hazard Survey (NOHS), conducted by NIOSH from 1972 to 1974, estimated 

that 1.35 million workers in 111,222 plants were potentially exposed to 1,2-dichloroethane in the 

workplace in 1970 (NIOSH 1976a). These estimates were derived from observations of the actual use of 

1,2-dichloroethane (5% of total estimate), the use of trade-name products known to contain 1,2-dichloroethane (3%), and the use of generic products suspected of containing the compound (92%). The largest 

numbers of exposed workers were employed in medical and other health services, automotive dealerships 

and service stations, and wholesale trade industries. The occupational groups with the largest numbers of 

exposed workers were automobile mechanics, registered nurses, heavy equipment mechanics, janitors, 

and machinists. 

Preliminary data from a second workplace survey, the National Occupational Exposure Survey (NOES), 

conducted by NIOSH from 1980 to 1983, indicated that 77,111 workers (including 32,891 females) in 

1,526 plants were potentially exposed to 1,2-dichloroethane in the workplace in 1980 (NIOSH 1984a). 

The largest numbers of exposed workers were employed in the apparel and other textile products, 

chemical and allied products, business services, and petroleum and coal products industries as machine 

operators, assemblers, production inspectors, checkers, and examiners. The estimates were based on 

direct observation by the surveyor of the actual use of the compound (68%) and observation of the use of 

trade name products known to contain 1,2-dichloroethane (32%). 
1,2-DICHLOROETHANE 176 

6. POTENTIAL FOR HUMAN EXPOSURE 

Neither the NOHS database nor the NOES database contains information on the frequency, level, or 

duration of exposure of workers to any of the chemicals listed therein. They provide only estimates of 

workers potentially exposed to the chemicals. There was a large potential for exposure to 1,2-dichloroethane in the workplace during its previous use as a grain fumigant, solvent, and diluent in open-system 

operations (NIOSH 1978a). 

1,2-Dichloroethane was detected at a mean concentration of 0.09 μg/m3

 in workplaces where smoking is 

not permitted and at a mean concentration of 0.03 μg/m3

 in workplaces where smoking is permitted 

(Heavner et al. 1996). These data are in contrast with the findings from the same study that showed a 

significantly higher concentration of 1,2-dichloroethane in the air of homes in which at least one family 

member smoked (see Section 6.4.1). 

Exposure of the population to 1,2-dichloroethane through releases to ambient air from a number of 

specific emission sources has been estimated (Kellam and Dusetzina 1980). The estimates, which are 

probably too high because of the current limited use of leaded fuels, are presented in Table 6-2. The EPA 

Total Exposure Assessment Methodology (TEAM) studies measured personal and outdoor exposures of 

about 800 people to 25 volatile organic compounds, including 1,2-dichloroethane (Wallace 1991). The 

people were selected to represent more than one million residents in a wide variety of urban, suburban, 

and rural areas. The mean measured exposure to 1,2-dichloroethane, which was based on a 24-hour 

exposure of .750 people in 6 urban areas, was reported to be 0.5 μg/m3

. The outdoor air concentration 

based on backyard measurements in 175 homes in 6 urban areas was 7 μg/m3

 (Wallace 1991). 

In addition to industrial releases of 1,2-dichloroethane to ambient air, the general population may have 

been exposed to this compound in indoor air through volatilization from consumer products and from 

potable water (Andelman 1985). 1,2-Dichloroethane was detected in the volatile emissions of cleaning 

agents and pesticides, recently glued wallpaper, and recently glued carpet at concentrations of 

236 μg/m3

 (58.2 ppb), 48±7.3 μg/m3 (12±1.8 ppb), and 15±1 μg/m3 (3.7±0.25 ppb), respectively (Wallace 

et al. 1987). Since 1,2-dichloroethane is no longer used in consumer products like cleaning agents and 

adhesives, this route of exposure is expected to be low today. 

1,2-Dichloroethane has been detected in the expired breath and urine of humans in a number of studies, 

following exposure of the test subjects to the compound in ambient air and drinking water (Barkley et al. 

1980; EPA 1982a; Wallace et al. 1984). 
1,2-DICHLOROETHANE 177 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-2. Estimated Population Exposure to 1,2-Dichloroethane Through 

Releases to Ambient Air From a Number of Specific Emission Sourcesa
 

Emission source Estimated population exposed Ambient air concentration (ppb) 

1,2-Dichloroethane 12,500,000 0.01 to $10 

manufacturing plants 

Chemical production 2,621,000 0.01–0.99 

facilities 

Gasoline service stationsb 1,000,000 0.01–0.029 

Automobile emissions 13,000,000 0.01–0.029 

Automobile refueling 30,000,000 <0.01 

a

Derived from Kellam and Dusetzina 1980 

b

Emissions from gasoline stations are in decline. 
 

1,2-DICHLOROETHANE 178 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.6 EXPOSURES OF CHILDREN 

This section focuses on exposures from conception to maturity at 18 years in humans. Differences from 

adults in susceptibility to hazardous substances are discussed in 3.7 Children’s Susceptibility. 

Children are not small adults. A child’s exposure may differ from an adult’s exposure in many ways. 

Children drink more fluids, eat more food, breathe more air per kilogram of body weight, and have a 

larger skin surface in proportion to their body volume. A child’s diet often differs from that of adults. 

The developing human’s source of nutrition changes with age: from placental nourishment to breast milk 

or formula to the diet of older children who eat more of certain types of foods than adults. A child’s 

behavior and lifestyle also influence exposure. Children crawl on the floor, put things in their mouths, 

sometimes eat inappropriate things (such as dirt or paint chips), and spend more time outdoors. Children 

also are closer to the ground, and they do not use the judgment of adults to avoid hazards (NRC 1993). 

There are no exposure studies or body burden measurements of 1,2-dichloroethane in children. 

1,2-Dichloroethane has been detected in both ambient outdoor and indoor air as discussed in 

Section 6.4.1 and inhalation of contaminated air likely represents the greatest route of potential exposure 

for children. 1,2-Dichloroethane has also been detected in drinking water, and therefore, ingestion of 

contaminated water is a possible source of exposure. 1,2-Dichloroethane been detected in human milk at 

concentrations ranging from 0.195 to 0.63 mg/100 mL of milk (EPA 1980a; Urusova 1953). Therefore, it 

is possible that children may be exposed to 1,2-dichloroethane from breast-feeding mothers, although no 

details of the analytical methodology were reported and, the sample size was not provided in this study. 

Current data on the concentration of 1,2-dichloroethane in breast milk are not available. 1,2-Dichloroethane was formerly used in certain consumer household products such as cleaning agents and adhesives. 

The use of any household products that contained 1,2-dichloroethane to clean floors or glue carpets may 

result in exposure since children often crawl on floors and play on carpets. The potential for exposure is 

expected to diminish with time since 1,2-dichloroethane volatilizes fairly rapidly. This is expected to be a 

relatively minor route of exposure since most of these products have probably been used up or discarded 

from the majority of households. 

1,2-Dichloroethane has been detected in several food products as discussed in Section 6.4.4, but 

consumption of these products should not disproportionately affect children. No data are available 

regarding the weight-adjusted intake of 1,2-dichloroethane. 1,2-Dichloroethane was formerly used as a 

fumigant, but is not currently registered for use in agricultural products in the United States, Canada, or 
1,2-DICHLOROETHANE 179 

6. POTENTIAL FOR HUMAN EXPOSURE 

the United Kingdom. Therefore, it is expected that exposure to 1,2-dichloroethane through food sources 

will continue to decrease. 

Children are unlikely to be exposed to 1,2-dichloroethane from parents’ clothing or other objects removed 

from the workplace because of its volatility. It is possible that exposure may arise from the exhaled 

breath of parents who are occupationally exposed to 1,2-dichloroethane, but no quantitative data are 

available to confirm this. 1,2-Dichloroethane has been detected in humans in a number of studies, 

following exposure of the test subjects to the compound in ambient air and drinking water (Barkley et al. 

1980; EPA 1982a; Wallace et al. 1984). 

There have been no documented exposures of children to1,2-dichloroethane from pica. Children are 

unlikely to be exposed to 1,2-dichloroethane from pica since the majority of 1,2-dichloroethane released 

to the environment is emitted to the atmosphere. Furthermore, much of the 1,2-dichloroethane released to 

soil is expected to volatilize to air or leach into subsurface soil and groundwater. 

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES 

Human exposure to 1,2-dichloroethane is expected to be highest among certain occupational groups (e.g., 

chemical and allied products industry workers) (NIOSH 1984a) and members of the general population 

living in the vicinity of industrial point emission sources (EPA 1985a) and hazardous waste sites. 

1,2-Dichloroethane has been detected in both ambient air and water in low concentrations (Fusillo et al. 

1985; Isacson et al. 1985; Juttner 1986; McDonald et al. 1988; Singh et al. 1982). No information was 

found regarding the number of people potentially exposed around hazardous waste sites. It was estimated 

that .15 million people living in the vicinity of manufacturing and formulation plants were potentially 

exposed to concentrations ranging from 0.01 to $10 ppb 1,2-dichloroethane in ambient air in the late 

1970s (Kellam and Dusetzina 1980). 

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 1,2-dichloroethane is available. Where adequate 

information is not available, ATSDR, in conjunction with the National Toxicology Program (NTP), is 
 

 

 

1,2-DICHLOROETHANE 180 

6. POTENTIAL FOR HUMAN EXPOSURE 

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 1,2-dichloroethane. 

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 1,2-dichloroethane
 

are well characterized to permit estimation of its environmental fate (see Chapter 4). No additional
 

studies are needed at this time.
 

Production, Import/Export, Use, Release, and Disposal. Information on the production and
 

use of 1,2-dichloroethane is available (Anonymous 1998; Archer 1979; Dow Chemical Company 1989b;
 

SRI 1998). Import and export data on 1,2-dichloroethane are also available (Anonymous 1998). More
 

information regarding the amount of 1,2-dichloroethane that is disposed of at hazardous waste sites or
 

abandoned would be useful. No current data are available on the amount of 1,2-dichloroethane disposed
 

of annually.
 

According to the Emergency Planning and Community Right-to-Know Act of 1986, 42 U.S.C.
 

Section 11023, industries are required to submit chemical release and off-site transfer information to the
 

EPA. The TRI, which contains this information for 1999, became available in 2001. This database will
 

be updated yearly and should provide a list of industrial production facilities and emissions.
 

Environmental Fate. The partitioning of 1,2-dichloroethane into air, water, and soil is well
 

established (Brüeggemann et al. 1991; Chiou et al. 1980; Dilling 1977; Dilling et al. 1975; EPA 1981,
 

1985a; Jeng et al. 1992; Jury et al. 1990; Pearson and McConnell 1975; Wilson et al. 1981). 

1,2-Dichloroethane is highly mobile in soil and is expected to leach into groundwater. Available
 

laboratory data are sufficient to estimate its atmospheric lifetime, but information on degradation rates in
 

soil and water are limited. Recent data indicates that 1,2-dichloroethane will biodegrade slowly in soil,
 

water, and groundwater under both aerobic and anaerobic conditions. Additional data regarding the
 
 

 

 

1,2-DICHLOROETHANE 181 

6. POTENTIAL FOR HUMAN EXPOSURE 

degradation rates of 1,2-dichloroethane in soil and water would be helpful in assessing its environmental 

fate. 

Bioavailability from Environmental Media. 1,2-Dichloroethane has been measured in the breath, 

blood, urine, and adipose tissue of humans (Barkley et al. 1980; EPA 1980a, 1982a; Wallace et al. 1989). 

Thus, it can be concluded that 1,2-dichloroethane is bioavailable from the environment. Good 

quantitative data that correlate varying levels in the environment with levels in the body and associated 

health effects are lacking. Data are lacking regarding the extent to which 1,2-dichloroethane can be 

absorbed from various media (e.g., soil). 

The health effects observed in humans following exposure to 1,2-dichloroethane are those generally 

associated with exposure to chlorinated hydrocarbons. Therefore, it may not be possible to correlate the 

exact levels of 1,2-dichloroethane in the environment with observed health effects in humans. The 

methodology to predict exposure levels of 1,2-dichloroethane from observed health effects is lacking. 

Food Chain Bioaccumulation. The limited experimental data on bioconcentration of 1,2-dichloroethane in aquatic organisms (Banerjee and Baughman 1991; Farrington 1991) and the physical and 

chemical properties of this compound indicate that bioconcentration and biomagnification are not likely 

to occur. However, experimental data on food chain biomagnification will aid in determining the 

potential for human exposure to 1,2-dichloroethane. 

Exposure Levels in Environmental Media. 1,2-Dichloroethane has been detected at low levels 

(ppb) in ambient urban and rural air (Class and Ballschmiter 1986; Cohen et al. 1989; EPA 1988b, 1991c; 

Juttner 1986; Kelly et al. 1994; Pellizzari et al. 1986; Singh et al. 1982, 1992), in outdoor and indoor air 

samples of residences located near hazardous waste disposal sites (Andelman 1985; Barkley et al. 1980; 

Heavner et al. 1996; LaRegina et al. 1986), and in surface water (Brown et al. 1984; EPA 1977a; 

Yamamoto et al. 1997), groundwater (Barbee 1994; Brown et al. 1984; Lesage et al. 1990; Plumb 1987; 

Westrick et al. 1984), drinking water (Barkley et al. 1980; Clark et al. 1986; Kelley 1985; Krill and 

Sonzogni 1986; Lam et al. 1994b; Steichen et al. 1988; Suffet et al. 1980), sediment (Bianchi et al. 1991; 

Oliver and Pugsley 1986), and food stuffs (Draft 1988, 1989, 1991; Gold 1980; Heikes and Hopper 1986, 

Heikes 1987; Miyahara et al. 1995; Rembold et al. 1989). Data on estimated human intake from all 

media have not been located. 
 

 

 

1,2-DICHLOROETHANE 182 

6. POTENTIAL FOR HUMAN EXPOSURE 

Reliable monitoring data for the levels of 1,2-dichloroethane in contaminated media at hazardous waste 

sites are needed so that the information obtained on environmental levels of 1,2-dichloroethane can be 

used in combination with the known body burden of 1,2-dichloroethane to assess the potential risk of 

adverse health effects in populations living in the vicinity of hazardous waste sites. 

Exposure Levels in Humans. Recent estimates of the size of the population occupationally 

exposed to 1,2-dichloroethane are not available, and monitoring data on workplace exposure levels 

(NIOSH 1984a) are generally inadequate. General population exposure estimates have been prepared by 

the EPA (1985a) for inhalation of the compound in ambient air, which is believed to be the most 

important route of exposure. However, the general population may also be exposed to low concentrations 

of 1,2-dichloroethane through ingestion of contaminated water and/or food. The use of old consumer 

products that contained 1,2-dichloroethane represents a possible, but most likely inconsequential potential 

exposure route. Quantitative information about the size of the exposed populations and the levels of 

exposure are generally incomplete. This information is necessary for assessing the need to conduct health 

studies on these populations. 

Exposures of Children. There is no information available on the exposure of children to 

1,2-dichloroethane. Children are most likely to be exposed to 1,2-dichloroethane via inhalation of 

ambient air. Ingestion of drinking water and food may also yield childhood exposures. Contact with 

older household products that contained 1,2-dichloroethane is possible, but is unlikely to be a major 

source of exposure since 1,2-dichloroethane is no longer used in most consumer products. Children are 

unlikely to be exposed to 1,2-dichloroethane from pica. Accurate data on the levels of 1,2-dichloroethane 

in children are needed to identify ways to reduce the potential exposure risks. 

Child health data needs relating to susceptibility are discussed in 3.12.2 Identification of Data Needs: 

Children’s Susceptibility. 

Exposure Registries. No exposure registries for 1,2-dichloroethane were located. This substance is 

not currently one of the compounds for which a subregistry has been established in the National Exposure 

Registry. The substance will be considered in the future when chemical selection is made for 

subregistries to be established. The information that is amassed in the National Exposure Registry 

facilitates the epidemiological research needed to assess adverse health outcomes that may be related to 

exposure to this substance. 
1,2-DICHLOROETHANE 183 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.8.2 Ongoing Studies 

A spectroscopic investigation of the factors that affect the mobility of 1,2-dichloroethane in soil and clay 

surfaces is being conducted by Dr. Farmer of the University of California, Riverside (FEDRIP 1999). 

This project, which is sponsored by the U.S. Department of Agriculture, should provide additional 

information regarding the movement and leaching potential of 1,2-dichloroethane in soil surfaces. No 

long-term research projects or other ongoing studies of occupational or general population exposures 

were identified. 

As part of the Third National Health and Nutrition Evaluation Survey, the Environmental Health 

Laboratory Sciences Division of the National Center for Environmental Health and Injury Control, 

Centers for Disease Control, will be analyzing human blood samples for 1,2-dichloroethane and other 

volatile organic compounds. These data will give an indication of the frequency of occurrence and 

background levels of these compounds in the general population. 

1,2-DICHLOROETHANE 185 

7. ANALYTICAL METHODS 

The purpose of this chapter is to describe the analytical methods that are available for detecting, 

measuring, and/or monitoring 1,2-dichloroethane, its metabolites, and other biomarkers of exposure and 

effect to 1,2-dichloroethane. 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 

Table 7-1 lists the analytical methods used for determining 1,2-dichloroethane in biological fluids and 

tissues. Gas chromatography/mass spectrophotometry (GC/MS) is the most commonly used analytical 

method for measuring 1,2-dichloroethane in breath, blood, and urine samples (Ashley et al. 1992; Barkley 

et al. 1980; Wallace et al. 1984, 1986). Sensitivity is in the low- to sub-ppb range. For blood samples, 

recovery is >74% (Ashley et al. 1992). Precision is adequate (<30% relative standard deviation [RSD]) 

(Ashley et al 1992). Recovery data were not reported for breath or urine samples. 

Glutathione-S-transferase (GST) was suggested as a biological marker to detect 1,2-dichloroethane in 

human erythrocytes (Ansari et al. 1987). 1,2-Dichloroethane inactivates GST in human erythrocytes. A 

dose-dependent reduction in GST with levels of 1,2-dichloroethane in human erythrocytes in situ was 

reported. However, because a similar response is also reported for acrolein, propylene oxide, styrene 

oxide, and ethylene dibromide, it is not possible to use measurement of GST activity in human 

erythrocytes to monitor exposure to 1,2-dichloroethane alone (Ansari et al. 1987). 

The presence of metabolites of 1,2-dichloroethane, such as 2-chloroethanol and monochloroacetic acid, in 

blood and urine could be used as an indicator of exposure to 1,2-dichloroethane (Monster 1986). 

However, similar metabolites may be found following exposure to other volatile organic compounds. 

This method is not presently used to determine exposure to 1,2-dichloroethane. Levels of thioethers 

could be determined analytically in the urine. No analytical measurement for these metabolites are given. 
Table 7-1. Analytical Methods for Determining 1,2-Dichloroethane in Biological Sa

Sample matrix Preparation method 

Analytical method 

Sample detection limit 

Percent recovery 

Breath Collect exhaled air in Tenax 

cartridge 

GC/MS-thermal desorption in a fused silica 

1 μg/m3 No data 

capillary column 

Breath Collect exhaled air in Tenax 

cartridge 

GC/MS-thermal desorption 

0.12 μg/m3 No data 

Human erythrocytes Separate erythrocytes from 

blood; wash and hemolyze; collect GST enzyme 

GST activity; not specified 

No data No data 

Blood/urine Heat at 50 EC; purge with 

helium; trap on Tenax GC sorbent 

GC/MS No data No data 

Blood Purge-and-trap blood sample GC/MS 0.012 ppb 74–116 

GC = gas chromatography; GST = glutathione-S-transferase; MS = mass spectrophotometry 
1,2-DICHLOROETHANE 187 

7. ANALYTICAL METHODS 

A pilot study attempted to show a correlation between the levels of halogenated compounds found in the 

environment and levels measured in blood and urine. The results, however, were not statistically 

significant (Barkley et al. 1980). The lack of correlation was attributed to differences in body metabolism 

between the individuals and small sample size. However, the applicability of GC/MS towards correlating 

environmental levels with body burden levels, given a large enough sample size, was demonstrated. 

More information on methods for the analysis of 1,2-dichloroethane in biological materials, including 

sample preparation techniques can be found in the references cited in Table 7-1. 

7.2 ENVIRONMENTAL SAMPLES 

Table 7-2 lists the methods used for analyzing 1,2-dichloroethane in environmental samples. GC/MS and 

GC combined with electron capture detection (ECD) are the most commonly used analytical methods for 

detecting 1,2-dichloroethane in air (Class and Ballschmiter 1986; Driss and Bouguerra 1991; EPA 1999d; 

Grimsrud and Rasmussen 1975; Hoyt and Smith 1991; Hsu et al. 1991; Jonsson and Berg 1980; Kessels 

et al. 1992; Kirshen and Almasi 1992; McClenny et al. 1991; NIOSH 1994; Pleil et al. 1988; Wallace et 

al. 1984), water, including drinking water, waste water, and tap water (EPA 1982b, 1984c, 1997; Garcia 

et al. 1992; Otson and Williams 1982; Wallace et al. 1984), sediment (Hiatt 1981), fish (Easley et al. 

1981; Hiatt 1981), and food (Daft 1987, 1988, 1989, 1991; Heikes 1987; Heikes and Hopper 1986). Air 

samples are generally collected on filters and desorbed or collected in canisters. For measuring 

1,2-dichloroethane in air samples, sensitivity is in the sub-ppb to low-ppt range for both GC/MS and 

GC/ECD. Recovery (>90%) and precision (3% RSD) are good (Hsu et al. 1991; Jonsson and Berg 1980). 

Purge-and-trap extraction methods are generally used when measuring volatile compounds such as 

1,2-dichloroethane in water samples. Sensitivity is in the low-to-sub-ppb and low-ppt range for GC/MS 

and GC/ECD. High performance gas chromatography (HRGC)/MS has also been used to measure the 

compound in water with similar sensitivity. Recovery and precision data were not reported. HRGC, with 

dual detection by ECD and flame ionization detectors (FID) or GC/FID can also be used to measure 

1,2-dichloroethane in drinking water and tap water (Driss and Bouguerra 1991; Kessels et al. 1992). 

Sensitivity for HRGC/ECD-FID is in the sub-ppb range with excellent recovery (100%) (Kessels et al. 

1992). Sensitivity data were not reported for GC/FID; however, recoveries were adequate (77.5%) (Driss 

and Bouguerra 1991). For both methods, precision was good (3.1-21% RSD) (Driss and Bouguerra 1991; 

Kessels et al. 1992). 
Table 7-2. Analytical Methods for Determining 1,2-Dichloroethane in Environmental S

Analytical Sample detection Percent 

Sample matrix Preparation method method limit recovery 

Air Collect whole air sample in GC/MS 0.3 ppb No data 

canister; preconcentrate volatile organics from air; treatment of water vapor 

Air Draw ambient air through a GC/MS In general the No data 

cartridge containing detection limit should 

approximately 1–2 g of Tenax. be 20 ng or less Certain volatile organic compounds are trapped on the Tenax while highly volatile organic compounds and most inorganic atmospheric constituents pass through the cartridge 

Air Draw ambient air through a GC/MS No data 85 

cartridge containing approximately 0.4 g of a carbon molecular sieve (CMS) adsorbant. Volatile organic compounds are captured on the adsorbant while major inorganic atmospheric constituents pass through (or are only partially retained) 

Air Purge-and-trap GC/ECD/FID For many compounds 100 

detection limits of 1–5 ng are found using FID 
Table 7-2. Analytical Methods for Determining 1,2-Dichloroethane in Environmental Sampl

Analytical Sample detection Percent 

Sample matrix Preparation method method limit recovery 

Air Workplace air Air and soil gas Drinking water Drinking water Water and waste water Water and waste water 

Draw a sample of ambient air 

through a sampling train comprised of components that regulate the rate and duration of sampling into a pre-evacuated SUMMA passivated canister 

Place the front and back sorbent 

sections of the sampler tube in separate vials. Discard the glass wool and foam plugs. Add 1 mL carbon disulfide to each vial 

Collect air or soil gas sample in 

evacuated canister or Tedlar bag through a cryogenically cooled trap to freeze out and preconcentrate volatile compounds; heat trap and transfer volatile analyte to cryogenically cooled column 

Purge-and-trap 

Liquid-liquid extraction using 

n-pentane Purge-and-trap Purge-and-trap 

GC/MS GC/FID HRGC/PID-ECD or ELCD 

GC/MS 

HRGC/ECD 

GC 

GC/PID 

>1 ppb 

0.2 mg/m3 

0.05 ppb (ELCD); 0.19 ppb (ECD) 

5 ng/L 

2.6 μg/L 

0.03 μg/L 

0.03 μg/L 

90–110 

No data No data 

No data 

No data 

1.04–1.06C 

97.8 

No data 
Table 7-2. Analytical Methods for Determining 1,2-Dichloroethane in Environmental Sampl

Analytical Sample detection Percent 

Sample matrix Preparation method method limit recovery 

Water and waste Purge-and-trap GC/MS 0.06 μg/L No data 

water Water and waste Grab sample GC/MS 4.7 μg/L 1.02+0.45C 

water 99 Water and waste Purge-and-trap GC/MS 10 μg/L 7.7 μg/L water Water and waste Modified purge-and-trap GC/HECD and 0.1 μg/L (FID); 78 (FID); 

water FID simultaneous <0.1 μg/L (HECD) 79 (HECD) Water, waste water, Purge-and-trap GC/MS 5 μg/kg No data 

and solid waste (soil/sediment); 

0.5 μg/kg (wastes); 5 μg/L (water) 

Water and waste Purge-and-trap GC 0.002μg/L No data water Drinking water Purge-and-trap extraction HRGC/ECD-FID 0.03 μg/L (ECD); 100 (ECD); 

technique 0.07 μg/L (FID) 104–116 (FID) 

Tap Water Purge-and-trap extraction GC/FID No data 77.5 

technique 

Water, solid waste, Vacuum distillation extraction GC/MS No data No data 

and tissue technique 
Table 7-2. Analytical Methods for Determining 1,2-Dichloroethane in Environmental Sampl

Sample matrix Preparation method 

Analytical method 

Sample detection limit 

Percent recovery 

Fish Add fish tissue to reagent grade 

water; disrupt cells ultrasonically; analyze sample by a purge-and ­trap method 

GC/MS 10 μg/kg 85±11 

Fish Spiked samples of ground fish 

tissue; vaporize VOCs from fish under vacuum and condense in 

GC/MS No data 85±11a 

purge-and-trap 

Fish Homogenize fish sample; 

remove residual moisture by vacuum distillation 

GC/MS-fused silica capillary column 

No data No data 

Sediment Spiked samples; vaporize VOCs 

under vacuum and condense in 

GC/MS No data 96±17a 

purge-and-trap 

Grains, legumes, spices, citrus fruits, beverages, dairy products, meat 

Acidified acetone-water extraction; isooctane back extraction 

GC/ECD No data 14–75 

Table ready foods Stirred with water; purge-andtrap on Tenax GC; hexane 

desorption 

GC/ECD 6 ppb 85–104 

aReported as percent spike recoveries for 25 ppb spikes ECD = electron capture detector; ELCD = electrolytic conductivity detector; FID = flame ionization detector; GC = gas chroHECD = Hall electron capture detector; HRGC = high resolution gas chromatography; MS = mass spectrometry; PID = phoVOCs = volatile organic carbon compounds
1,2-DICHLOROETHANE 192 

7. ANALYTICAL METHODS 

The EPA recommends GC/MS for the determination of 1,2-dichloroethane in water and waste water; this 

method can detect 1,2-dichloroethane levels of $0.03 μg/L (EPA 1997). Under EPA's Contract 

Laboratory Program, all contract laboratories are required to maintain certain levels of performance to 

meet specific quantitation levels (EPA 1988c). For volatiles such as 1,2-dichloroethane, the Contract 

Required Quantitation Level (CRQL) for water and low soil/sediment is 5 μg/L (EPA 1986a). Complete 

descriptions of these techniques can be found in the references cited in Table 7-2. 

GC/MS is adequate for measuring 1,2-dichloroethane in fish samples with sensitivities in the low-ppb 

range. Good recoveries (>85%) were achieved (Easley et al. 1981; Hiatt 1981). Sensitivity data were not 

reported for measuring 1,2-dichloroethane in sediment; however, good recovery (96%) was obtained 

(Hiatt 1981). 

GC/ECD is generally used to measure 1,2-dichloroethane in foodstuffs (Daft 1987, 1988, 1989, 1991; 

Heikes 1987; Heikes and Hopper 1986). For table-ready foods, sensitivity is in the low-ppb range with 

good recoveries achieved (>85%) (Heikes 1987; Heikes and Hopper 1986). Precision data were not 

reported. 

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 1,2-dichloroethane is available. Where adequate 

information is not available, ATSDR, in conjunction with the National Toxicology Program (NTP), is 

required to assure the initiation of a program of research designed to determine the health effects (and 

techniques for developing methods to determine such health effects) of 1,2-dichloroethane. 

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. 
 

 

1,2-DICHLOROETHANE 193 

7. ANALYTICAL METHODS 

7.3.1 Identification of Data Needs 

Methods for Determining Biomarkers of Exposure and Effect. The activity of the biomarker 

GST in blood (Ansari et al. 1987) cannot be used reliably as an indication of exposure to 1,2-dichloroethane because similar effects have been noted following exposure to other organic compounds. No 

method is routinely used to monitor 1,2-dichloroethane metabolites in human urine. Although it has been 

suggested that measurement of 2-chloroethanol and monochloroacetic acid in urine may provide evidence 

of exposure to chlorinated hydrocarbons (Monster 1986), these metabolites are not specific to 

1,2-dichloroethane. Methods are available to detect and quantify 1,2-dichloroethane in human breath, 

blood, and urine (Ashley et al. 1992; Barkley et al. 1980; Wallace et al. 1984). There are no quantitative 

techniques available to correlate the concentration of 1,2-dichloroethane measured in expired air, blood, 

or urine to levels of environmental exposure or health effects. 

Methods for Determining Parent Compounds and Degradation Products in Environmental 

Media. Methods are available to detect 1,2-dichloroethane in air (Class and Ballschmiter 1986; Driss 

and Bouguerra 1991; EPA 1999d; Grimsrud and Rasmussen 1975; Hoyt and Smith 1991; Hsu et al. 1991; 

Jonsson and Berg 1980; Kessels et al. 1992; Kirshen and Almasi 1992; McClenny et al. 1991; NIOSH 

1994; Pleil et al. 1988; Wallace et al. 1984), water, including drinking water, waste water, and tap water 

(EPA 1997; Garcia et al. 1992; Otson and Williams 1982; Wallace et al. 1984), sediment (Hiatt 1981), 

fish (Easley et al. 1984; Hiatt 1981), and food (Daft 1987, 1988, 1989, 1991; Heikes 1987; Heikes and 

Hopper 1986). The standardized methods can detect 1,2-dichloroethane levels of $5 ppt in air and of 

$2 ng/L in water. In addition, numerous techniques for the analysis of 1,2-dichloroethane are reported in 

the open literature. 

The known degradation products of 1,2-dichloroethane that contain chlorine are volatile organic 

compounds and are often detected and quantified along with 1,2-dichloroethane in monitoring 

experiments (although they probably arose from anthropogenic sources). Thus, experimental methods 

used to detect 1,2-dichloroethane are sufficient to quantify its chlorinated degradation products. 

7.3.2 Ongoing Studies 

No ongoing studies were located regarding techniques for measuring or detecting 1,2-dichloroethane in 

biological materials or environmental samples. 
1,2-DICHLOROETHANE 194 

7. ANALYTICAL METHODS 

The Environmental Health Laboratory Sciences Division of the National Center for Environmental Health 

and Injury Control, Centers for Disease Control, is developing methods for the analysis of 1,2-dichloroethane and other volatile organic compounds in blood. These methods use purge and trap methodology, 

high resolution gas chromatography, and magnetic sector mass spectrometry that permit detection limits 

in the low parts per trillion (ppt) range. 
1,2-DICHLOROETHANE 195 

8. REGULATIONS AND ADVISORIES
 

The international, national, and state regulations and guidelines pertaining to 1,2-dichloroethane in air, 

water, and food are summarized in Table 8-1. 

MRLs for inhalation and oral exposure to 1,2-dichloroethane were derived by ATSDR (see Section 2.5 of 

this toxicological profile). An MRL of 0.6 ppm for chronic-duration inhalation exposure (15–364 days) 

is based on a NOAEL for liver histopathology in rats (Cheever et al. 1990). An MRL of 0.2 mg/kg/day 

for intermediate-duration oral exposure (15–364 days) to 1,2-dichloroethane is based on a LOAEL for 

increased absolute and relative kidney weights in rats (NTP 1991a). 

No oral RfD or inhalation RfC toxicity values have been derived for 1,2-dichloroethane by the EPA (IRIS 

1999). EPA has determined that 1,2-dichloroethane is a probable human carcinogen (B2 classification) 

and derived a slope factor (q1*) of 0.091 (mg/kg/day)-1 for cancer risk associated with exposure to 

1,2-dichloroethane (IRIS 1999). Similarly, the International Agency for Research on Cancer (IARC) has 

classified 1,2-dichloroethane as a Group 2B carcinogen (possibly carcinogenic to humans) (IARC 1987). 

1,2-Dichloroethane is on the list of chemicals appearing in "Toxic Chemicals Subject to Section 313 of 

the Emergency Planning and Community Right-to-Know Act of 1986" (EPA 1987a). 
 

 

1,2-DICHLOROETHANE 196 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to 1,2-Dichloroethane 

Agency Description	 Information References 

INTERNATIONAL 

Guidelines: 

IARC Carcinogenicity classification Group 2Ba IARC 2001 

WHO Inhalation carcinogenic potency 0.36–2.0 μg/m3 WHO 2001a 

(50,000-fold less than the 

estimated carcinogenic potential) 

Drinking water (lifetime cancer 30 μg/L WHO 2001b
 

risk of 10-5)
 

NATIONAL 

Regulations and 

Guidelines: 

a. Air 

ACGIH TLV–TWA 10 ppm ACGIH 2000 

NIOSH REL (10-hour TWA) 1 ppm NIOSH 2001 

STEL 2 ppm 

IDLH 50 ppm 

Potential occupational carcinogen 

OSHA	 PEL (8-hour TWA) 50 ppm OSHA 2001b 

PEL (ceiling) 100 ppm 

PEL (maximum peak above 200 ppm 

ceiling concentration for an
 

8-hour shift for a maximum
 

duration of 5 minutes in any
 

3-hours)
 

PEL (8-hour TWA) for 50 ppm OSHA 2001c 

construction industry 29CFR1926.55 

PEL (8-hour TWA) for shipyard 50 ppm OSHA 2001a 

industry 29CFR1915.1000 

USC	 HAP USC 2001
 

42USC7412
 

b. Water 

EPA	 Drinking water standard 5x10-3 mg/L EPA 2001g 

40CFR141.32 
1,2-DICHLOROETHANE 197 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to 1,2-Dichloroethane 

(continued) 

Agency Description Information References 

NATIONAL (cont.) 

EPA Groundwater monitoring 

Suggest method 

PQL 

8010 8240 

0.5 μgL 5 μgL 

EPA 2001f 

40CFR264 

Appendix IX 

MCLG 0 mg/L EPA 2001h 

40CFR141.50 

MCL 5x10-3 mg/L EPA 2001i 

40CFR141.61 

Water pollution—hazardous 

substance designation 

EPA 2001m 

40CFR116.4 

Water programs—determination 

of reportable quantity 

100 pounds EPA 2001n 

40CFR117.3 

Water quality criteria for human 

health for consumption of: 

Water and organism 

Organism only 

0.38 μg/Lb 

99 μg/Lb 

EPA 2001a 

c. Food 

FDA Bottled water—concentration limit 5x10-3 mg/L FDA 2000d 

21CFR165.110 

Chemicals used to wash or to not to exceed FDA 2000f 

assist in the peeling of fruits and 

vegetables 

0.2 ppm 21CFR173.315 

(a)(3) 

Food additives permitted for 

direct addition—adjuvants for 

pesticide use dilutions 

FDA 2000b 

21CFR172.710 

Food additives permitted in feed 

and drinking water of animals: 

Used as a solvent in the 

FDA 2000e 

21CFR573.440 

extraction processing of 

animal byproducts for use 

in animal feeds 

Maximum quantity of the 

additive permitted to remain 

on the extracted byproducts 

not to exceed 

300 ppm 

Extracted animal byproduct 

added as a source of protein 

to all rations consistent with 

not to exceed 13% 

of the total ration 

good feeding practices 
1,2-DICHLOROETHANE 198 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to 1,2-Dichloroethane 

(continued) 

Agency Description	 Information References 

NATIONAL (cont.) 

FDA	 Indirect food additives FDA 2000g 

—adhesives and components of 21CFR175.105 

coatings (c)(5) 

Indirect food additives FDA 2000c 

—polycarbonate resins 21CFR177.1580(b) 

Secondary direct food additive for 30 ppm FDA 2000a 

human consumption 21CFR173.230 

d. Other 

ACGIH	 Carcinogenicity classification A4c ACGIH 2000 

DOT Reportable quantity 100 pounds	 DOT 2001 

49CFR172.101 

Appendix A 

EPA	 Carcinogenicity classification Group B2d EPA 2001b 

Cancer slope factor (oral) 9.1x10-2	 IRIS 2001 

Carcinogenic drinking water unit 6.7x10-3 (μg/L)-1 

risk 

Carcinogenic inhalation unit risk 2.6x10-5 (μg/m3

)

-1 

Chemical information rules EPA 2001c 

—chemical lists and reporting 40CFR712.30 

periods 

Effective date	 08/04/95 

Reporting date	 10/03/95 

Community Right-to-Know; toxic 01/01/87 EPA 2001d 

chemical release reporting 40CFR372.65 

—effective date 

Health and environmental EPA 2001e 

protection standards at uranium 40CFR192 

and thorium mill tailings—listed Appendix I 

constituent 

Identification and listing of U077 EPA 2000 

hazardous waste 40CFR261.33(f) 

Reportable quantity 100 pounds	 EPA 2001j 

40CFR302.4 

RfC not established	 IRIS 2001 

RfD	 not established 
1,2-DICHLOROETHANE 199 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to 1,2-Dichloroethane 

(continued) 

Agency Description Information References 

NATIONAL (cont.) 

EPA Risk specific doses 

Unit risk 

RsD 

2.6x10-5 μg/L 

3.8x10-1 μg/L 

EPA 2001k 

40CFR266 

Appendix V 

TSCA—health and safety data 

reporting 

Effective date 

Sunset date 

06/01/87 

06/01/87 

EPA 2001l 

40CFR716.120 

STATE 

Regulations and 

Guidelines: 

a. Air 

California Toxic air contaminant California 2001 

California REL 95 μg/m3 

Colorado Fence line air quality criteria for 

remediation: 

Cancer 

Noncancer 

0.10 μg/m3 

4.9 μg/m3 

Colorado 2000 

Kansas Ambient air quality standard 0.8 tons/year CDC 1999b 

New Jersey Required use of a MSHA/NIOSH 

approved supplied-air respirator 

$1 ppm New Jersey 

Department of 

Health 1994 

b. Water 

Alabama MCL 0.5 mg/L ADEM 2000 

Alaska MCL 0.005 mg/L ADEC 2000 

Groundwater clean-up level 0.005 mg/L 

Arizona Drinking water guideline 0.38 μg/L HSDB 2001 

Arkansas MCL 0.5 mg/L APCEC 2000 

California Drinking water standard 0.5 μg/L HSDB 2001 

Connecticut Notification threshold 

concentration: 

Drinking water well 

Groundwater 

1 μg/L 

1 μg/L 

CDEP 2000b 

Florida Drinking water standard 3 μg/L HSDB 2001 
1,2-DICHLOROETHANE 200 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to 1,2-Dichloroethane 

(continued) 

Agency Description Information References 

STATE (cont.) 

Georgia Instream concentration 98.6 μg/L GDNR 2000 

Hawaii MCL 0.005 mg/L Hawaii Department 

of Health 1997 

Maine Drinking water guideline 5 μg/L HSDB 2001 

Massachusetts MCL 0.05 mg/L FSTRAC 1999a 

Minnesota Drinking water guideline 4 μg/L HSDB 2001 

New Jersey Drinking water standard 2 μg/L HSDB 2001 

South Dakota Human health standards 5x10-3 mg/L FSTRAC 1999b 

contaminant level 

c. Other 

California Carcinogenicity classification California 2001 

Cancer potency factor (oral) 7.0x10-2 mg/kg/day 

Cancer potency factor 2.2x10-5 (μg/m3

)

-1 

(inhalation) 

Colorado Chronic fence line criteria Colorado 2000 

Cancer 0.1 μg/m3 

Noncancer 4.9 μg/m3 

Hazardous air pollutant (HAP) list 1.000 fm305e Colorado 2001 

Connecticut Hazardous waste contaminant 0.5 mg/L CDEP 1996 

level 

a

Group 2B: possible human carcinogen

b

This criterion is based on carcinogenicity of 10-6 risk. Alternate risk levels may be obtained by moving the decimal 

point (e.g., for a risk level of 10-5, move the decimal point in the recommended criterion one place to the right). c

A4: not classifiable as a human carcinogen

d

Group B2: not classifiable as a human carcinogen 

e

fm305: method 305 fraction measure factor 

ACGIH = American Conference of Governmental Industrial Hygienists; ADEC = Alaska Department of Environmental 

Conservation; ADEM = Alabama Department of Environmental Management; APCEC = Arkansas Pollution Control 

and Ecology Commission; CDC = Center for Disease Control; CDEP = Connecticut Department of Environmental 

Protection; CFR = Code of Federal Regulations; DOT = Department of Transportation; EPA = Environmental 

Protection Agency; FDA = Food and Drug Administration; FSTRAC = Federal–State Toxicology Risk Analysis 

Committee; GDNR = Georgia Department of Natural Resources; HAP = hazardous air pollutant; HSDB = Hazardous 

Substances Data Bank; IARC = International Agency for Research on Cancer; IDLH = immediately dangerous to life 

and health; IRIS = Integrated Risk Information System; MCL = maximum contaminant level; MCLG = maximum 

contaminant level goal; MSHA = Mining Safety and Health Administration; NIOSH = National Institute of Occupational 

Safety and Health; OSHA = Occupational Safety and Health Administration; PEL = permissible exposure limit; 

PQL = practical quantity limit; REL = recommended exposure limit; RfC = oral reference concentration; RfD = oral 

reference dose; RsD = risk specific dose; STEL = short-term exposure limit; TLV = threshold limit value; 

TSCA = Toxic Substances Control Act; TWA = time-weighted average; USC = United States Code; WHO = World 

Health Organization 
______________ 

1,2-DICHLOROETHANE 201 

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1,2-DICHLOROETHANE 247 

10. GLOSSARY 

Absorption—The taking up of liquids by solids, or of gases by solids or liquids. 

Acute Exposure—Exposure to a chemical for a duration of 14 days or less, as specified in the 

Toxicological Profiles. 

Adsorption—The adhesion in an extremely thin layer of molecules (as of gases, solutes, or liquids) to the 

surfaces of solid bodies or liquids with which they are in contact. 

Adsorption Coefficient (Koc)—The ratio of the amount of a chemical adsorbed per unit weight of organic 

carbon in the soil or sediment to the concentration of the chemical in solution at equilibrium. 

Adsorption Ratio (Kd)—The amount of a chemical adsorbed by a sediment or soil (i.e., the solid phase) 

divided by the amount of chemical in the solution phase, which is in equilibrium with the solid phase, at a 

fixed solid/solution ratio. It is generally expressed in micrograms of chemical sorbed per gram of soil or 

sediment. 

Benchmark Dose (BMD)—Usually defined as the lower confidence limit on the dose that produces a 

specified magnitude of changes in a specified adverse response. For example, a BMD10 would be the 

dose at the 95% lower confidence limit on a 10% response, and the benchmark response (BMR) would be 

10%. The BMD is determined by modeling the dose response curve in the region of the dose response 

relationship where biologically observable data are feasible. 

Benchmark Dose Model—A statistical dose-response model applied to either experimental toxicological 

or epidemiological data to calculate a BMD. 

Bioconcentration Factor (BCF)—The quotient of the concentration of a chemical in aquatic organisms at 

a specific time or during a discrete time period of exposure divided by the concentration in the 

surrounding water at the same time or during the same period. 

Biomarkers—Broadly defined as indicators signaling events in biologic systems or samples. They have 

been classified as markers of exposure, markers of effect, and markers of susceptibility. 

Cancer Effect Level (CEL)—The lowest dose of chemical in a study, or group of studies, that produces 

significant increases in the incidence of cancer (or tumors) between the exposed population and its 

appropriate control. 

Carcinogen—A chemical capable of inducing cancer. 

Case-Control Study—A type of epidemiological study which examines the relationship between a 

particular outcome (disease or condition) and a variety of potential causative agents (such as toxic 

chemicals). In a case-controlled study, a group of people with a specified and well-defined outcome is 

identified and compared to a similar group of people without outcome. 

Case Report—Describes a single individual with a particular disease or exposure. These may suggest 

some potential topics for scientific research but are not actual research studies. 
1,2-DICHLOROETHANE 248 

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 which examines the 

relationship between exposure and outcome to a chemical or to chemicals at one point in time. 

Data Needs—Substance-specific informational needs that if met would reduce the uncertainties of human 

health assessment. 

Developmental Toxicity—The occurrence of adverse effects on the developing organism that may result 

from exposure to a chemical prior to conception (either parent), during prenatal development, or 

postnatally to the time of sexual maturation. Adverse developmental effects may be detected at any point 

in the life span of the organism. 

Dose-Response Relationship—The quantitative relationship between the amount of exposure to a 

toxicant and the incidence of the adverse effects. 

Embryotoxicity and Fetotoxicity—Any toxic effect on the conceptus as a result of prenatal exposure to a 

chemical; the distinguishing feature between the two terms is the stage of development during which the 

insult occurs. The terms, as used here, include malformations and variations, altered growth, and in utero 

death. 

Environmental Protection Agency (EPA) Health Advisory—An estimate of acceptable drinking water 

levels for a chemical substance based on health effects information. A health advisory is not a legally 

enforceable federal standard, but serves as technical guidance to assist federal, state, and local officials. 

Epidemiology—Refers to the investigation of factors that determine the frequency and distribution of 

disease or other health-related conditions within a defined human population during a specified period. 

Genotoxicity—A specific adverse effect on the genome of living cells that, upon the duplication of 

affected cells, can be expressed as a mutagenic, clastogenic or carcinogenic event because of specific 

alteration of the molecular structure of the genome. 

Half-life—A measure of rate for the time required to eliminate one half of a quantity of a chemical from 

the body or environmental media. 

Immediately Dangerous to Life or Health (IDLH)—The maximum environmental concentration of a 

contaminant from which one could escape within 30 minutes without any escape-impairing symptoms or 

irreversible health effects. 
1,2-DICHLOROETHANE 249 

10. GLOSSARY 

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. 

Immunologic Toxicity—The occurrence of adverse effects on the immune system that may result from 

exposure to environmental agents such as chemicals. 

Immunological Effects—Functional changes in the immune response. 

In Vitro—Isolated from the living organism and artificially maintained, as in a test tube. 

In Vivo—Occurring within the living organism. 

Lethal Concentration(LO) (LCLO)—The lowest concentration of a chemical in air which has been reported 

to have caused death in humans or animals. 

Lethal Concentration(50) (LC50)—A calculated concentration of a chemical in air to which exposure for a 

specific length of time is expected to cause death in 50% of a defined experimental animal population. 

Lethal Dose(LO) (LDLO)—The lowest dose of a chemical introduced by a route other than inhalation that 

has been reported to have caused death in humans or animals. 

Lethal Dose(50) (LD50)—The dose of a chemical which has been calculated to cause death in 50% of a 

defined experimental animal population. 

Lethal Time(50) (LT50)—A calculated period of time within which a specific concentration of a chemical is 

expected to cause death in 50% of a defined experimental animal population. 

Lowest-Observed-Adverse-Effect Level (LOAEL)—The lowest exposure level of chemical in a study, or 

group of studies, that produces statistically or biologically significant increases in frequency or severity of 

adverse effects between the exposed population and its appropriate control. 

Lymphoreticular Effects—Represent morphological effects involving lymphatic tissues such as the 

lymph nodes, spleen, and thymus. 

Malformations—Permanent structural changes that may adversely affect survival, development, or 

function. 

Minimal Risk Level (MRL)—An estimate of daily human exposure to a hazardous substance that is 

likely to be without an appreciable risk of adverse noncancer health effects over a specified route and 

duration of exposure. 

Modifying Factor (MF)—A value (greater than zero) that is applied to the derivation of a minimal risk 

level (MRL) to reflect additional concerns about the database that are not covered by the uncertainty 

factors. The default value for a MF is 1. 

Morbidity—State of being diseased; morbidity rate is the incidence or prevalence of disease in a specific 

population. 
1,2-DICHLOROETHANE 250 

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) which represents the best estimate of relative risk (risk as a ratio of the 

incidence among subjects exposed to a particular risk factor divided by the incidence among subjects who 

were not exposed to the risk factor). An odds ratio of greater than 1 is considered to indicate greater risk 

of disease in the exposed group compared to the unexposed. 

Organophosphate or Organophosphorus Compound—A phosphorus containing organic compound and 

especially a pesticide that acts by inhibiting cholinesterase. 

Permissible Exposure Limit (PEL)—An Occupational Safety and Health Administration (OSHA) 

allowable exposure level in workplace air averaged over an 8-hour shift of a 40-hour workweek. 

Pesticide—General classification of chemicals specifically developed and produced for use in the control 

of agricultural and public health pests. 

Pharmacokinetics—The science of quantitatively predicting the fate (disposition) of an exogenous 

substance in an organism. Utilizing computational techniques, it provides the means of studying the 

absorption, distribution, metabolism and excretion of chemicals by the body. 

Pharmacokinetic Model—A set of equations that can be used to describe the time course of a parent 

chemical or metabolite in an animal system. There are two types of pharmacokinetic models: data-based 

and physiologically-based. A data-based model divides the animal system into a series of compartments 

which, in general, do not represent real, identifiable anatomic regions of the body whereby the 

physiologically-based model compartments represent real anatomic regions of the body. 

Physiologically Based Pharmacodynamic (PBPD) Model—A type of physiologically-based doseresponse model which quantitatively describes the relationship between target tissue dose and toxic end 

points. These models advance the importance of physiologically based models in that they clearly 

describe the biological effect (response) produced by the system following exposure to an exogenous 

substance. 
1,2-DICHLOROETHANE 251 

10. GLOSSARY 

Physiologically Based Pharmacokinetic (PBPK) Model—Comprised of a series of compartments 

representing organs or tissue groups with realistic weights and blood flows. These models require a 

variety of physiological information: tissue volumes, blood flow rates to tissues, cardiac output, alveolar 

ventilation rates and, possibly membrane permeabilities. The models also utilize biochemical information 

such as air/blood partition coefficients, and metabolic parameters. PBPK models are also called 

biologically based tissue dosimetry models. 

Prevalence—The number of cases of a disease or condition in a population at one point in time. 

Prospective Study—A type of cohort study in which the pertinent observations are made on events 

occurring after the start of the study. A group is followed over time. 

q1

*—The upper-bound estimate of the low-dose slope of the dose-response curve as determined by the 

multistage procedure. The q1* can be used to calculate an estimate of carcinogenic potency, the 

incremental excess cancer risk per unit of exposure (usually μg/L for water, mg/kg/day for food, and 

μg/m3

 for air). 

Recommended Exposure Limit (REL)—A National Institute for Occupational Safety and Health 

(NIOSH) time-weighted average (TWA) concentrations for up to a 10-hour workday during a 40-hour 

workweek. 

Reference Concentration (RfC)—An estimate (with uncertainty spanning perhaps an order of magnitude) 

of a continuous inhalation exposure to the human population (including sensitive subgroups) that is likely 

to be without an appreciable risk of deleterious noncancer health effects during a lifetime. The inhalation 

reference concentration is for continuous inhalation exposures and is appropriately expressed in units of 

mg/m3 or ppm. 

Reference Dose (RfD)—An estimate (with uncertainty spanning perhaps an order of magnitude) of the 

daily exposure of the human population to a potential hazard that is likely to be without risk of deleterious 

effects during a lifetime. The RfD is operationally derived from the no-observed-adverse-effect level 

(NOAEL-from animal and human studies) by a consistent application of uncertainty factors that reflect 

various types of data used to estimate RfDs and an additional modifying factor, which is based on a 

professional judgment of the entire database on the chemical. The RfDs are not applicable to 

nonthreshold effects such as cancer. 

Reportable Quantity (RQ)—The quantity of a hazardous substance that is considered reportable under the 

Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA). Reportable 

quantities are (1) 1 pound or greater or (2) for selected substances, an amount established by regulation 

either under CERCLA or under Section 311 of the Clean Water Act. Quantities are measured over a 

24-hour period. 

Reproductive Toxicity—The occurrence of adverse effects on the reproductive system that may result 

from exposure to a chemical. The toxicity may be directed to the reproductive organs and/or the related 

endocrine system. The manifestation of such toxicity may be noted as alterations in sexual behavior, 

fertility, pregnancy outcomes, or modifications in other functions that are dependent on the integrity of 

this system. 

Retrospective Study—A type of cohort study based on a group of persons known to have been exposed at 

some time in the past. Data are collected from routinely recorded events, up to the time the study is 

undertaken. Retrospective studies are limited to causal factors that can be ascertained from existing 

records and/or examining survivors of the cohort. 
1,2-DICHLOROETHANE 252 

10. GLOSSARY 

Risk—The possibility or chance that some adverse effect will result from a given exposure to a chemical. 

Risk Factor—An aspect of personal behavior or lifestyle, an environmental exposure, or an inborn or 

inherited characteristic, that is associated with an increased occurrence of disease or other health-related 

event or condition. 

Risk Ratio—The ratio of the risk among persons with specific risk factors compared to the risk among 

persons without risk factors. A risk ratio greater than 1 indicates greater risk of disease in the exposed 

group compared to the unexposed. 

Short-Term Exposure Limit (STEL)—The American Conference of Governmental Industrial Hygienists 

(ACGIH) maximum concentration to which workers can be exposed for up to 15 min continually. No 

more than four excursions are allowed per day, and there must be at least 60 min between exposure 

periods. The daily Threshold Limit Value - Time Weighted Average (TLV-TWA) may not be exceeded. 

Target Organ Toxicity—This term covers a broad range of adverse effects on target organs or 

physiological systems (e.g., renal, cardiovascular) extending from those arising through a single limited 

exposure to those assumed over a lifetime of exposure to a chemical. 

Teratogen—A chemical that causes structural defects that affect the development of an organism. 

Threshold Limit Value (TLV)—An American Conference of Governmental Industrial Hygienists 

(ACGIH) concentration of a substance to which most workers can be exposed without adverse effect. 

The TLV may be expressed as a Time Weighted Average (TWA), as a Short-Term Exposure Limit 

(STEL), or as a ceiling limit (CL). 

Time-Weighted Average (TWA)—An allowable exposure concentration averaged over a normal 8-hour 

workday or 40-hour workweek. 

Toxic Dose(50) (TD50)—A calculated dose of a chemical, introduced by a route other than inhalation, 

which is expected to cause a specific toxic effect in 50% of a defined experimental animal population. 

Toxicokinetic—The study of the absorption, distribution and elimination of toxic compounds in the 

living organism. 

Uncertainty Factor (UF)—A factor used in operationally deriving the Minimal Risk Level (MRL) or 

Reference Dose (RfD) or Reference Concentration (RfC) from experimental data. UFs are intended to 

account for (1) the variation in sensitivity among the members of the human population, (2) the 

uncertainty in extrapolating animal data to the case of human, (3) the uncertainty in extrapolating from 

data obtained in a study that is of less than lifetime exposure, and (4) the uncertainty in using lowestobserved-adverse-effect level (LOAEL) data rather than no-observed-adverse-effect level (NOAEL) data. 

A default for each individual UF is 10; if complete certainty in data exists, a value of one can be used; 

however a reduced UF of three may be used on a case-by-case basis, three being the approximate 

logarithmic average of 10 and 1. 

Xenobiotic—Any chemical that is foreign to the biological system. 
1,2-DICHLOROETHANE A-1 

APPENDIX A
 

ATSDR MINIMAL RISK LEVEL 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. 
1,2-DICHLOROETHANE A-2 

APPENDIX A 

MRLs are intended only to serve as a screening tool to help public health professionals decide where to 

look more closely. They may also be viewed as a mechanism to identify those hazardous waste sites that 

are not expected to cause adverse health effects. Most MRLs contain a degree of uncertainty because of 

the lack of precise toxicological information on the people who might be most sensitive (e.g., infants, 

elderly, nutritionally or immunologically compromised) to the effects of hazardous substances. ATSDR 

uses a conservative (i.e., protective) approach to address this uncertainty consistent with the public health 

principle of prevention. Although human data are preferred, MRLs often must be based on animal studies 

because relevant human studies are lacking. In the absence of evidence to the contrary, ATSDR assumes 

that humans are more sensitive to the effects of hazardous substance than animals and that certain persons 

may be particularly sensitive. Thus, the resulting MRL may be as much as a hundredfold below levels 

that have been shown to be nontoxic in laboratory animals. 

Proposed MRLs undergo a rigorous review process: Health Effects/MRL Workgroup reviews within the 

Division of Toxicology, expert panel peer reviews, and agencywide MRL Workgroup reviews, with 

participation from other federal agencies and comments from the public. They are subject to change as 

new information becomes available concomitant with updating the toxicological profiles. Thus, MRLs in 

the most recent toxicological profiles supersede previously published levels. For additional information 

regarding MRLs, please contact the Division of Toxicology, Agency for Toxic Substances and Disease 

Registry, 1600 Clifton Road, Mailstop E-29, Atlanta, Georgia 30333. 
1,2-DICHLOROETHANE A-3 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEETS 

Chemical name: 1,2-Dichloroethane 

CAS number(s): 107-06-2 

Date: May 11, 2001 

Profile status: Draft 3 

Route: [X ] Inhalation [ ] Oral 

Duration: [ ] Acute [ ] Intermediate [X] Chronic 

Key to figure: 48 

Species: Rat 

MRL: 0.6 [ ] mg/kg/day [X] ppm [ ] mg/m3 

Reference: Cheever KL, Cholakis JM, el-Hawari AM, et al. 1990. Ethylene dichloride: The influence of 

disulfiram or ethanol on oncogenicity, metabolism, and DNA covalent binding in rats. Fundam Appl 

Toxicol 14: 243-261. 

Experimental design: Groups of 50 male and 50 female Sprague-Dawley rats were exposed to 50 ppm 

1,2-dichloroethane for 7 hours/day, 5 days/week for 2 years. Additional rats were similarly exposed to 

50 ppm with either 0.05% disulfiram in the diet or 5% ethanol in the drinking water. Signs of toxicity, 

body weight and food consumption were evaluated during the study, and comprehensive gross and 

histological examinations were performed at the end of the exposure period. 

Effects noted in study and corresponding doses: The only effect associated with exposure to 

1,2-dichloroethane alone was a slight increase in the incidence of unspecified basophilic focal cellular 

changes in the pancreas in female rats. The significance of the pancreatic changes is unclear because the 

incidence was not reported, dose-response cannot be assessed because only one exposure level was tested, 

the effect was induced in only one sex, and the study was designed to evaluate carcinogenicity. 

Effects due to combined exposure to 1,2-dichloroethane and disulfuram included increased kidney lesions 

(chronic nephropathy, calculi of the renal pelvis, and hyperplasia of the pelvic epithelium) in males, 

increased liver lesions (mostly bile duct cysts) in both sexes, and increased tumor incidences in both sexes 

(intrahepatic bile duct cholangiomas in males and females, mammary neoplasms in females, testicular 

interstitial cell tumors in males). No significant increases in tumor incidences were found after exposure 

to either 1,2-dichloroethane alone or in combination with ethanol. Congestion of the mesenteric lymph 

node was reported in both disulfuram-only and disulfuram/1,2-dichloroethane combined treatment groups 

to a similar extent and appears to be related to disulfuram exposure. Disulfuram, a known inhibitor of the 

microsomal aldehyde dehyderogenase system, apparently produced an overall decrease in the rate of 

biotransformation, leading to increased blood levels of 1,2-dichloroethane which may have contributed to 

the carcinogenic effect of combined exposure. 

Dose and end point used for MRL derivation: 

The 50 ppm exposure concentration is a NOAEL for histopathology in the liver and other tissues. 

[X ] NOAEL [ ] LOAEL 
1,2-DICHLOROETHANE A-4 

APPENDIX A 

Uncertainty factors used in MRL derivation: 

[X]	 3 for interspecies extrapolation since a dosimetric adjustment was applied to the exposure 

concentration 

[X]	 10 for human variability 

[X] 3 used as a modifying factor to account for database deficiencies 

Was a conversion factor used from ppm in food or water to a mg/body weight dose?
 

Not applicable. 

Was a conversion used from intermittent to continuous exposure?
 

No conversion from intermittent to continuous exposure was used since blood levels of
 

1,2-dichloroethane reach equilibrium within 2 to 3 hours of the onset of inhalation exposure (see 

Section 2.3.1.1). 

If an inhalation study in animals, list conversion factors used in determining human equivalent dose: 

The human equivalent concentration (NOAEL[HEC]) was determined following U.S. EPA (1994; Methods 

for Derivation of Inhalation Reference Concentrations and Application of Inhalation Dosimetry), Section 

4.3.6.2 (Remote (Extrarespiratory) Effects) for exposure to Category 3 gases. The equation used for 

obtaining the NOAEL[HEC] from the NOAEL (50 ppm) is as follows: 

NOAEL[HEC] = NOAEL[ADJ] x [(Hb/g)A)/(Hb/g)H )] 

where, 

NOAEL[HEC] = human equivalent NOAEL (ppm) 

NOAEL[ADJ] = exposure-adjusted NOAEL (ppm) [no adjustment was used] 

(Hb/g)A and (Hb/g )H = blood/gas partition coefficient for animals (A) and humans (H) 

(unitless) 

The following default value was used: 

(Hb/g)A / (Hb/g)H = 1 (unitless). 

Empirical blood/gas partition coefficients were available for rats and humans (Gargas et al. 1989). 

However, the default value of 1 was used for both rat and human blood/gas partition coefficients, since
 

(Hb/g)A > (Hb/g)H (U.S. EPA 1994).
 

The NOAEL[HEC] was calculated as follows:
 

NOAEL[HEC] = 50 ppm x (1) = 50 ppm 

Application of an uncertainty factor of 90 (3 for interspecies extrapolation, 10 for human variability, and 

3 for database deficiencies) results in a chronic duration inhalation MRL of 0.6 ppm. 
1,2-DICHLOROETHANE A-5 

APPENDIX A 

Other additional studies or pertinent information that lend support to this MRL: 

The MRL is based on a free-standing NOAEL for liver histopathology. Although other concentrations of 

1,2-dichloroethane were not tested, there is confidence in the NOAEL due to the number of animals 

(50/sex) and scope of histological examinations. Additionally, the liver is a documented target of 

1,2-dichloroethane toxicity in several acute and intermediate-duration inhalation studies (Heppel et al. 

1946; Spencer et al. 1951), as well as in a number of studies of orally-exposed animals. Limitations in 

the acute and intermediate inhalation studies preclude considering them as the basis for derivation of an 

MRL for intermediate-duration inhalation exposure, but the weight-of-evidence indicates that NOAELs 

for hepatotoxicity in the intermediate-duration studies are higher than the chronic liver NOAEL. 

Consequently, the chronic-duration inhalation MRL of 0.6 ppm is also expected to be protective of toxic 

effects after intermediate duration inhalation exposures to 1,2-dichloroethane. 

Agency Contact (Chemical Manager): Malcolm Williams 
 

 

1,2-DICHLOROETHANE A-6 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEETS 

Chemical name: 1,2-Dichloroethane 

CAS number(s): 107-06-2 

Date: May 11, 2001 

Profile status: Draft 3 

Route: [ ] Inhalation [X] Oral 

Duration: [ ] Acute [X] Intermediate [ ] Chronic 

Key to figure: 25 

Species: Rat 

MRL: 0.2 [X] mg/kg/day [ ] ppm [ ] mg/m3 

Reference: NTP. 1991a. Toxicity studies of 1,2-dichloroethane (ethylene dichloride) (CAS No. 

107-06-2) in F344/N rats, Sprague Dawley rats, Osborne-Mendel rats and B6C3F1 mice (drinking water 

and gavage studies). Research Triangle Park, NC: U.S. Department of Health and Human Services, 

Public Health Service, National Institute of Health, National Toxicology Program. NIH Publication No. 

91-3123. 

Experimental design: Groups of F344/N rats, Sprague-Dawley rats, Osborne-Mendel rats, and B6C3F1 

mice (10 animals/sex/strain) were exposed to drinking water containing 0, 500, 1,000, 2,000, 4,000, or 

8,000 ppm of 1,2-dichloroethane for 13 weeks. The high concentration was close to the solubility limit 

for 1,2-dichloroethane in water. Reported estimates of intake from the water were 0, 49-60, 86-99, 

146-165, 259-276, and 492-518 mg/kg/day in the male rats and 0, 58-82, 102-126, 172-213, 311-428, and 

531-727 mg/kg/day in the female rats. Intake estimates in the mice were 0, 249, 448, 781, 2,710, and 

4,207 mg/kg/day in males and 0, 244, 647, 1,182, 2,478, and 4,926 mg/kg/day in females. Additional 

groups of F344/N rats (10/sex) were administered 1,2-dichloroethane by gavage on 5 days/week for 

13 weeks to compare toxicity resulting from bolus administration with that of the continuous exposure in 

drinking water. Gavage doses were 0, 30, 60, 120, 240, and 480 mg/kg in the male rats and 0, 18, 37, 75, 

150, and 300 mg/kg in the female rats. Signs of toxicity, body weight, food and water consumption, 

hematology, and serum chemistry were evaluated throughout the study, and comprehensive gross and 

histological examinations were performed at the end of the exposure period. 

Effects noted in study and corresponding doses: Rat drinking water studies: Dose-related decreased 

water consumption occurred in all strains and both sexes. There was >10% reduction in body weight gain 

at $259 mg/kg in male F344/N rats, 518 mg/kg in male Sprague-Dawley rats, and 492 mg/kg in male 

Osborne-Mendel rats. There were no significant reductions in body weight gain in female rats of any 

strain. Liver weight and/or liver:body weight ratio significantly increased at $147 mg/kg in F344/N 

males and 102, 320, and 601 mg/kg in females; at $60 mg/kg in Sprague-Dawley males and 531 mg/kg in 

females; and at $88 mg/kg in Osborne-Mendel males. Kidney weight and/or kidney:body weight ratio 

significantly increased at $58 and $86 mg/kg in F344/N females and males, respectively; at $60 and 

$76 mg/kg in Sprague-Dawley males and females, respectively; and at $82 and $88 mg/kg in 

Osborne-Mendel females and males, respectively. There was a dose-related increase in the incidence of 

renal tubular regeneration (minimal to mild) in F344/N females at $58 mg/kg/day; incidences 

progressively increased from 1/10 at 102 mg/kg/day to 9/10 at 601 mg/kg/day. 

Mouse drinking water study: No mortality except in 90% of high-dose females. Body weight gain 

significantly reduced in high-dose males. Increased liver weight/liver:body weight ratio, significant at 

$249 mg/kg/day in males and $647 mg/kg/day in females. Increased kidney weight and kidney:body 

weight ratio, significant at $448 mg/kg/day in males and $244 mg/kg/day in females. Increased tubular 
 

1,2-DICHLOROETHANE A-7 

APPENDIX A 

regeneration (minimal to moderate) in males, increasing in incidence from 1/10 at 249 mg/kg/day to 

9/10 at $4,207 mg/kg/day. Karyomegaly, dilatation, protein casts, and mineralization in kidneys also 

occurred in males at 4,207 mg/kg/day. 

Rat gavage study: Deaths occurred in all males at $240 mg/kg and 90% of females at 300 mg/kg; clinical 

signs preceding death included tremors, salivation, and emaciation. Pathology in moribund/dead animals 

included necrosis in the thymus and cerebellum. Small but significant changes in various hematological 

parameters occurred in higher dose groups and were considered to be indicative of dehydration and 

attributed to significantly reduced in water consumption (60% compared to controls). No effects on 

growth at sublethal doses. Other effects included minimal to mild hyperplasia and inflammation of the 

forestomach epithelium (sometimes with foci of necrosis and mineralization) in 5/10 males at 240 mg/kg, 

3/10 males at 480 mg/kg, and 3/10 females at 300 mg/kg. Liver weight and liver:body weight ratio 

significantly increased in males at 120 mg/kg (no data from higher doses due to mortality) and females at 

all doses (appears dose-related). Kidney weight and/or kidney:body weight ratio significantly increased 

in males at $30 mg/kg and $75 mg/kg in females. Kidney weight changes appeared to be dose-related, 

but no renal histopathological changes were observed. 

Dose and end point used for MRL derivation: 

The lowest dose in female rats, 58 mg/kg/day, is a LOAEL for kidney effects. The increased kidney 

weight is considered to be an early-stage adverse effect because dose-related renal histopathology (tubular 

regeneration, indicative of previous tubular injury with subsequent repair) developed at higher doses in 

the same strain of rats. 

[X ] NOAEL [ ] LOAEL 

Uncertainty factors used in MRL derivation: 

[X] 3 for use of a minimal LOAEL 

[X] 10 for interspecies extrapolation 

[X] 10 for human variability 

Was a conversion factor used from ppm in food or water to a mg/body weight dose? 

Estimated daily doses were reported by the investigators. 

Was a conversion used from intermittent to continuous exposure? 

Not applicable. 

If an inhalation study in animals, list conversion factors used in determining human equivalent dose: 

Not applicable. 
1,2-DICHLOROETHANE A-8 

APPENDIX A 

Other additional studies or pertinent information that lend support to this MRL: 

1,2-Dichloroethane is acutely nephrotoxic in humans following both inhalation and ingestion; renal 

effects observed in people who died following acute high-level exposure included diffuse necrosis, 

tubular necrosis, and kidney failure (Hueper and Smith 1935; Lochhead and Close 1951; Nouchi et al. 

1984; Yodaiken and Babcock 1973). Renal effects (e.g., increased kidney weight and tubular epithelial 

degeneration) were also found in animals following high-level acute- and intermediate-duration inhalation 

exposure (Heppel et al. 1946; NTP 1991a; Spencer et al. 1951). Reports of increased relative kidney 

weight in rats that were treated with $75 or 90 mg/kg/day by gavage for 90 days (Daniel et al. 1994; van 

Esch et al. 1977) are supportive of the 58 mg/kg/day LOAEL used to derive the MRL. 

Agency Contact (Chemical Manager): Malcolm Williams 
1,2-DICHLOROETHANE 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, 

weight-of-evidence discussions for human health end points by addressing the following questions. 

1.	 What effects are known to occur in humans? 

2.	 What effects observed in animals are likely to be of concern to humans? 

3.	 What exposure conditions are likely to be of concern to humans, especially around hazardous 

waste sites? 

The chapter covers end points in the same order they appear within the Discussion of Health Effects by 

Route of Exposure section, by route (inhalation, oral, dermal) and within route by effect. Human data are 

presented first, then animal data. Both are organized by duration (acute, intermediate, chronic). In vitro 

data and data from parenteral routes (intramuscular, intravenous, subcutaneous, etc.) are also considered 

in this chapter. If data are located in the scientific literature, a table of genotoxicity information is 

included. 

The carcinogenic potential of the profiled substance is qualitatively evaluated, when appropriate, using 

existing toxicokinetic, genotoxic, and carcinogenic data. ATSDR does not currently assess cancer 

potency or perform cancer risk assessments. Minimal risk levels (MRLs) for noncancer end points (if 

derived) and the end points from which they were derived are indicated and discussed. 

Limitations to existing scientific literature that prevent a satisfactory evaluation of the relevance to public 

health are identified in the Chapter 3 Data Needs section. 
1,2-DICHLOROETHANE B-2 

APPENDIX B 

Interpretation of Minimal Risk Levels 

Where sufficient toxicologic information is available, we have derived minimal risk levels (MRLs) for 

inhalation and oral routes of entry at each duration of exposure (acute, intermediate, and chronic). These 

MRLs are not meant to support regulatory action; but to acquaint health professionals with exposure 

levels at which adverse health effects are not expected to occur in humans. They should help physicians 

and public health officials determine the safety of a community living near a chemical emission, given the 

concentration of a contaminant in air or the estimated daily dose in water. MRLs are based largely on 

toxicological studies in animals and on reports of human occupational exposure. 

MRL users should be familiar with the toxicologic information on which the number is based. Chapter 2, 

"Relevance to Public Health," contains basic information known about the substance. Other sections such 

as Chapter 3 Section 3.9, "Interactions with Other Substances,” and Section 3.10, "Populations that are 

Unusually Susceptible" provide important supplemental information. 

MRL users should also understand the MRL derivation methodology. MRLs are derived using a 

modified version of the risk assessment methodology the Environmental Protection Agency (EPA) 

provides (Barnes and Dourson 1988) to determine reference doses for lifetime exposure (RfDs). 

To derive an MRL, ATSDR generally selects the most sensitive end point which, in its best judgement, 

represents the most sensitive human health effect for a given exposure route and duration. ATSDR 

cannot make this judgement or derive an MRL unless information (quantitative or qualitative) is available 

for all potential systemic, neurological, and developmental effects. If this information and reliable 

quantitative data on the chosen end point are available, ATSDR derives an MRL using the most sensitive 

species (when information from multiple species is available) with the highest NOAEL that does not 

exceed any adverse effect levels. When a NOAEL is not available, a lowest-observed-adverse-effect 

level (LOAEL) can be used to derive an MRL, and an uncertainty factor (UF) of 10 must be employed. 

Additional uncertainty factors of 10 must be used both for human variability to protect sensitive 

subpopulations (people who are most susceptible to the health effects caused by the substance) and for 

interspecies variability (extrapolation from animals to humans). In deriving an MRL, these individual 

uncertainty factors are multiplied together. The product is then divided into the inhalation concentration 

or oral dosage selected from the study. Uncertainty factors used in developing a substance-specific MRL 

are provided in the footnotes of the LSE Tables. 

Chapter 3 

Health Effects 

Tables and Figures for Levels of Significant Exposure (LSE) 

Tables (3-1, 3-2, and 3-3) and figures (3-1 and 3-2) are used to summarize health effects and illustrate 

graphically levels of exposure associated with those effects. These levels cover health effects observed at 

increasing dose concentrations and durations, differences in response by species, minimal risk levels 

(MRLs) to humans for noncancer end points, and EPA's estimated range associated with an upper- bound 

individual lifetime cancer risk of 1 in 10,000 to 1 in 10,000,000. Use the LSE tables and figures for a 

quick review of the health effects and to locate data for a specific exposure scenario. The LSE tables and 

figures should always be used in conjunction with the text. All entries in these tables and figures 

represent studies that provide reliable, quantitative estimates of No-Observed-Adverse-Effect Levels 

(NOAELs), Lowest-Observed-Adverse-Effect Levels (LOAELs), or Cancer Effect Levels (CELs). 
1,2-DICHLOROETHANE B-3 

APPENDIX B 

The legends presented below demonstrate the application of these tables and figures. Representative 

examples of LSE Table 3-1 and Figure 3-1 are shown. The numbers in the left column of the legends 

correspond to the numbers in the example table and figure. 

LEGEND 

See LSE Table 3-1 

(1)	 Route of Exposure One of the first considerations when reviewing the toxicity of a substance using 

these tables and figures should be the relevant and appropriate route of exposure. When sufficient 

data exists, three LSE tables and two LSE figures are presented in the document. The three LSE 

tables present data on the three principal routes of exposure, i.e., inhalation, oral, and dermal (LSE 

Table 3-1, 3-2, and 3-3, respectively). LSE figures are limited to the inhalation (LSE Figure 3-1) 

and oral (LSE Figure 3-2) routes. Not all substances will have data on each route of exposure and 

will not therefore have all five of the tables and figures. 

(2)	 Exposure Period Three exposure periods - acute (less than 15 days), intermediate (15–364 days), 

and chronic (365 days or more) are presented within each relevant route of exposure. In this 

example, an inhalation study of intermediate exposure duration is reported. For quick reference to 

health effects occurring from a known length of exposure, locate the applicable exposure period 

within the LSE table and figure. 

(3)	 Health Effect The major categories of health effects included in LSE tables and figures are death, 

systemic, immunological, neurological, developmental, reproductive, and cancer. NOAELs and 

LOAELs can be reported in the tables and figures for all effects but cancer. Systemic effects are 

further defined in the "System" column of the LSE table (see key number 18). 

(4)	 Key to Figure Each key number in the LSE table links study information to one or more data points 

using the same key number in the corresponding LSE figure. In this example, the study represented 

by key number 18 has been used to derive a NOAEL and a Less Serious LOAEL (also see the 2 

"18r" data points in Figure 3-1). 

(5)	 Species The test species, whether animal or human, are identified in this column. Chapter 2, 

"Relevance to Public Health," covers the relevance of animal data to human toxicity and 

Section 3.4, "Toxicokinetics," contains any available information on comparative toxicokinetics. 

Although NOAELs and LOAELs are species specific, the levels are extrapolated to equivalent 

human doses to derive an MRL. 

(6)	 Exposure Frequency/Duration The duration of the study and the weekly and daily exposure 

regimen are provided in this column. This permits comparison of NOAELs and LOAELs from 

different studies. In this case (key number 18), rats were exposed to 1,1,2,2-tetrachloroethane via 

inhalation for 6 hours per day, 5 days per week, for 3 weeks. For a more complete review of the 

dosing regimen refer to the appropriate sections of the text or the original reference paper, i.e., 

Nitschke et al. 1981. 

(7)	 System This column further defines the systemic effects. These systems include: respiratory, 

cardiovascular, gastrointestinal, hematological, musculoskeletal, hepatic, renal, and dermal/ocular. 

"Other" refers to any systemic effect (e.g., a decrease in body weight) not covered in these systems. 

In the example of key number 18, 1 systemic effect (respiratory) was investigated. 
1,2-DICHLOROETHANE B-4 

APPENDIX B 

(8)	 NOAEL A No-Observed-Adverse-Effect Level (NOAEL) is the highest exposure level at which no 

harmful effects were seen in the organ system studied. Key number 18 reports a NOAEL of 3 ppm 

for the respiratory system which was used to derive an intermediate exposure, inhalation MRL of 

0.005 ppm (see footnote "b"). 

(9)	 LOAEL A Lowest-Observed-Adverse-Effect Level (LOAEL) is the lowest dose used in the study 

that caused a harmful health effect. LOAELs have been classified into "Less Serious" and 

"Serious" effects. These distinctions help readers identify the levels of exposure at which adverse 

health effects first appear and the gradation of effects with increasing dose. A brief description of 

the specific end point used to quantify the adverse effect accompanies the LOAEL. The respiratory 

effect reported in key number 18 (hyperplasia) is a Less serious LOAEL of 10 ppm. MRLs are not 

derived from Serious LOAELs. 

(10)	 Reference The complete reference citation is given in Chapter 9 of the profile. 

(11)	 CEL A Cancer Effect Level (CEL) is the lowest exposure level associated with the onset of 

carcinogenesis in experimental or epidemiologic studies. CELs are always considered serious 

effects. The LSE tables and figures do not contain NOAELs for cancer, but the text may report 

doses not causing measurable cancer increases. 

(12)	 Footnotes Explanations of abbreviations or reference notes for data in the LSE tables are found in 

the footnotes. Footnote "b" indicates the NOAEL of 3 ppm in key number 18 was used to derive an 

MRL of 0.005 ppm. 

LEGEND 

See Figure 3-1 

LSE figures graphically illustrate the data presented in the corresponding LSE tables. Figures help the 

reader quickly compare health effects according to exposure concentrations for particular exposure 

periods. 

(13)	 Exposure Period The same exposure periods appear as in the LSE table. In this example, health 

effects observed within the intermediate and chronic exposure periods are illustrated. 

(14)	 Health Effect These are the categories of health effects for which reliable quantitative data exists. 

The same health effects appear in the LSE table. 

(15)	 Levels of Exposure concentrations or doses for each health effect in the LSE tables are graphically 

displayed in the LSE figures. Exposure concentration or dose is measured on the log scale "y" axis. 

Inhalation exposure is reported in mg/m3

 or ppm and oral exposure is reported in mg/kg/day. 

(16)	 NOAEL In this example, 18r NOAEL is the critical end point for which an intermediate inhalation 

exposure MRL is based. As you can see from the LSE figure key, the open-circle symbol indicates 

to a NOAEL for the test species-rat. 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 38r is 1 of 3 studies for which Cancer Effect Levels were derived. The diamond 

symbol refers to a Cancer Effect Level for the test species-mouse. The number 38 corresponds to 

the entry in the LSE table. 
1,2-DICHLOROETHANE B-5 

APPENDIX B 

(18)	 Estimated Upper-Bound Human Cancer Risk Levels This is the range associated with the 

upper-bound 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. 
2 

SAMPLE 

6 Table 3-1. Levels of Significant Exposure to [Chemical x] – Inhalation 1 

3 4 

Key to figurea Species 

Exposure frequency/ duration System 

NOAEL (ppm) 

6 INTERMEDIATE EXPOSURE 

5 6 7 8 

6 Systemic 9 9 9 96 18 Rat 13 wk 

5 d/wk 6 hr/d 

Resp 3b 

CHRONIC EXPOSURE Cancer 38 Rat 18 mo 

5 d/wk 7 hr/d 

39 Rat 89–104 wk 

5 d/wk 6 hr/d 

40 Mouse 79–103 wk 

5 d/wk 6 hr/d 

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

LOAEL (effect) 

Less serious (ppm) Serious (ppm) 

9 

9 

10 (hyperplasia) 

11 

9

20 (CEL, multiple 

organs) 

10 (CEL, lung tumors

nasal tumors) 

10 (CEL, lung tumors

hemangiosarcom

b Used to derive an intermediate inhalation Minimal Risk Level (MRL) of 5 x 10-3 ppm; dose adjusted for intermittent ex

an uncertainty factor of 100 (10 for extrapolation from animal to humans, 10 for human variability). 12 6


1,2-DICHLOROETHANE C-1 

APPENDIX C 

ACRONYMS, ABBREVIATIONS, AND SYMBOLS 

ACGIH American Conference of Governmental Industrial Hygienists 

ADI Acceptable Daily Intake 

ADME Absorption, Distribution, Metabolism, and Excretion 

AFID alkali flame ionization detector 

AFOSH Air Force Office of Safety and Health 

AML acute myeloid leukemia 

AOAC Association of Official Analytical Chemists 

atm atmosphere 

ATSDR Agency for Toxic Substances and Disease Registry 

AWQC Ambient Water Quality Criteria 

BAT Best Available Technology 

BCF bioconcentration factor 

BEI Biological Exposure Index 

BSC Board of Scientific Counselors 

C Centigrade 

CAA Clean Air Act 

CAG Cancer Assessment Group of the U.S. Environmental Protection Agency 

CAS Chemical Abstract Services 

CDC Centers for Disease Control and Prevention 

CEL Cancer Effect Level 

CELDS Computer-Environmental Legislative Data System 

CERCLA Comprehensive Environmental Response, Compensation, and Liability Act 

CFR Code of Federal Regulations 

Ci curie 

CL ceiling limit value 

CLP Contract Laboratory Program 

cm centimeter 

CML chronic myeloid leukemia 

CNS central nervous system 

CPSC Consumer Products Safety Commission 

CWA Clean Water Act 

d day 

Derm dermal 

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 

DOT/UN/ Department of Transportation/United Nations/ 

NA/IMCO North America/International Maritime Dangerous Goods Code 

DWEL Drinking Water Exposure Level 

ECD electron capture detection 

ECG/EKG electrocardiogram 
 

1,2-DICHLOROETHANE C-2 

APPENDIX C 

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 

ft foot 

FR Federal Register 

g gram 

GC gas chromatography 

Gd gestational day 

gen generation 

GLC gas liquid chromatography 

GPC gel permeation chromatography 

HPLC high-performance liquid chromatography 

hr hour 

HRGC high resolution gas chromatography 

HSDB Hazardous Substance Data Bank 

IDLH Immediately Dangerous to Life and Health 

IARC International Agency for Research on Cancer 

ILO International Labor Organization 

in inch 

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 

LCLo lethal concentration, low 

LC50 lethal concentration, 50% kill 

LDLo lethal dose, low 

LD50 lethal dose, 50% kill 

LT50 lethal time, 50% kill 

LOAEL lowest-observed-adverse-effect level 

LSE Levels of Significant Exposure 

m meter 

MA trans,trans-muconic acid 

MAL Maximum Allowable Level 

mCi millicurie 

MCL Maximum Contaminant Level 

MCLG Maximum Contaminant Level Goal 

mg milligram 

min minute 

mL milliliter 
1,2-DICHLOROETHANE C-3 

APPENDIX C 

mm millimeter 

mm Hg millimeters of mercury 

mmol millimole 

mo month 

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 

NCI National Cancer Institute 

NIEHS National Institute of Environmental Health Sciences 

NIOSH National Institute for Occupational Safety and Health 

NIOSHTIC NIOSH's Computerized Information Retrieval System 

NFPA National Fire Protection Association 

ng nanogram 

NLM National Library of Medicine 

nm nanometer 

NHANES National Health and Nutrition Examination Survey 

nmol nanomole 

NOAEL no-observed-adverse-effect level 

NOES National Occupational Exposure Survey 

NOHS National Occupational Hazard Survey 

NPD nitrogen phosphorus detection 

NPDES National Pollutant Discharge Elimination System 

NPL National Priorities List 

NR not reported 

NRC National Research Council 

NS not specified 

NSPS New Source Performance Standards 

NTIS National Technical Information Service 

NTP National Toxicology Program 

ODW Office of Drinking Water, EPA 

OERR Office of Emergency and Remedial Response, EPA 

OHM/TADS Oil and Hazardous Materials/Technical Assistance Data System 

OPP Office of Pesticide Programs, EPA 

OPPTS Office of Prevention, Pesticides and Toxic Substances, EPA 

OPPT Office of Pollution Prevention and Toxics, EPA 

OSHA Occupational Safety and Health Administration 

OSW Office of Solid Waste, EPA 

OTS Office of Toxic Substances 

OW Office of Water 

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 

PID photo ionization detector 
1,2-DICHLOROETHANE C-4 

APPENDIX C 

pg picogram 

pmol picomole 

PHS Public Health Service 

PMR proportionate mortality ratio 

ppb parts per billion 

ppm parts per million 

ppt parts per trillion 

PSNS Pretreatment Standards for New Sources 

REL recommended exposure level/limit 

RfC Reference Concentration 

RfD Reference Dose 

RNA ribonucleic acid 

RTECS Registry of Toxic Effects of Chemical Substances 

RQ Reportable Quantity 

SARA Superfund Amendments and Reauthorization Act 

SCE sister chromatid exchange 

sec second 

SIC Standard Industrial Classification 

SIM selected ion monitoring 

SMCL Secondary Maximum Contaminant Level 

SMR standard 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 Compound 

TPQ Threshold Planning Quantity 

TRI Toxics Release Inventory 

TSCA Toxic Substances Control Act 

TRI Toxics Release Inventory 

TWA time-weighted average 

U.S. United States 

UF uncertainty factor 

VOC Volatile Organic Compound 

yr year 

WHO World Health Organization 

wk week 

> 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 
1,2-DICHLOROETHANE C-5 

APPENDIX C 

μg microgram q1

* cancer slope factor 

– negative 

+ positive 

(+) weakly positive result 

(–) weakly negative result 

1,2-DICHLOROETHANE D-1 

APPENDIX D
 

INDEX 

absorption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11, 94-98, 107, 115, 116, 126, 127, 133, 145, 146, 172
 

ACGIH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 192, 194, 196
 

acute dermal exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133 
 

acute inhalation exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14, 18, 23, 37, 43, 132, 133
 

acute oral exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14, 72, 140 
 

adenocarcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147 
 

adipose tissue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94, 95, 99, 106, 107, 118, 127, 145, 146, 150, 178
 

aerobic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165-167, 177
 

Agency for Toxic Substances and Disease Registry (see ATSDR) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9, 10 
 

AHH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93 
 

air . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-6, 8, 9, 11, 12, 38-40, 43, 45, 86, 87, 94-96, 98, 103, 105-108, 111, 115, 120, 123, 127, 

132, 154, 155, 159, 160, 162, 165, 167-170, 172-179, 182-185, 189, 191, 192, 195, 196
 

ALT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40, 41, 76, 122, 144
 

ambient air . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11, 12, 160, 167-169, 173, 174, 176, 179, 184, 185, 195
 

anaerobic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162, 165, 167, 177
 

AST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40, 41, 122, 144
 

ATSDR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9, 10, 12, 21, 22, 122, 129, 176, 177, 188, 191
 

bioaccumulation ................................................................................. 100, 178
 

bioavailability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178 
 

bioconcentration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11, 164, 178
 

biomagnification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178 
 

biomarker . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119-121, 138, 144, 189
 

birth weight . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 
 

blood . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8, 12, 14, 23, 38, 40, 50, 74, 75, 94-101, 103, 104, 106-109, 112, 113, 115, 117-120, 

123, 126, 135, 140, 144, 145, 149, 150, 178, 180-183, 189, 190
 

body weight effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43, 79, 86 
 

breast milk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8, 11, 95, 97, 98, 100, 107, 118, 120, 127, 128, 144-146, 150, 175
 

cancer . . . . . . . . . . . . . . . . . . . . . . . . . . 4, 5, 9, 17, 22, 48, 83-85, 87, 109, 113, 115, 131, 134, 143, 151, 153, 191, 192, 194-196
 

carcinogen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5, 9, 17, 131, 135, 136, 143, 191, 192, 196
 

carcinogenic . . . . . . . . . . . . . . . . . . . . . . 12, 17, 21, 22, 49, 50, 84, 85, 87, 109, 111, 113, 125, 131, 134-136, 151, 191, 192, 194
 

carcinogenicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17, 43, 48, 84, 85, 87, 88, 111, 125, 134-136, 145, 147, 192, 194, 196
 

cardiovascular effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15, 38, 73 
 

children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6, 7, 11, 101, 115-118, 126, 147, 148, 150, 151, 175, 176, 179
 

Department of Health and Human Services (see DHHS) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5, 17 
 

dermal effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43, 78, 86 
 

DHHS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5, 17, 135 
 

diet . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1, 75, 123, 127, 175
 

DNA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17, 87-93, 112, 119, 121, 124, 135-137, 144, 147
 

drinking water . . . . . . . . . . 3, 4, 7, 9, 11-15, 19, 72-85, 97, 104, 112, 116, 117, 123, 125, 131-133, 135, 138-144, 149, 150, 160,
 

167, 169, 170, 172, 173, 175, 176, 178, 179, 183, 185, 186, 189, 192-196
 

endocrine effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42, 43, 78 
 

endometriosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114 
 

Environmental Protection Agency (see EPA) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1, 8, 12, 153, 196
 

EPA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1, 5, 8, 9, 12, 17, 22, 85, 95, 114, 118, 124, 129, 131, 136, 150, 153, 156, 159, 

160, 164, 165, 168-173, 175-179, 181, 183-186, 188, 189, 191-196
 

exposure levels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15, 22, 23, 40, 43, 50, 81, 83, 103, 133, 142, 143, 149, 178, 179
 

FDA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8, 171, 193, 194, 196
 

Fedrip . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151, 180
 

fiber . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46, 143, 147
 

fish . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2, 164, 183, 186-189
 

Food and Drug Administration (see FDA) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8, 196 
 

gas chromatography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121, 181-183, 187, 190
 

gastrointestinal effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39, 73 
 

general population . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11, 119, 144, 160, 172, 173, 176, 179, 180
 

genotoxic effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23, 50, 87, 88, 91, 136, 137
 
1,2-DICHLOROETHANE D-2 

APPENDIX D 

gestational age . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 
 

half-life . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11, 107, 119, 160, 165-167
 

hematological effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39, 40, 74, 80, 81, 116, 148
 

Henry’s law . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154, 163
 

hepatic effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13, 40, 41, 75, 76 
 

hepatocellular carcinomas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17, 84, 135 
 

hydrolysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11, 121, 160, 163, 165, 166
 

hydroxyl radical . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165 
 

IARC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5, 17, 136, 156, 191, 192, 196
 

IgM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19, 116 
 

immunoglobulin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14, 80, 122, 140
 

immunological effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14, 44, 45, 79, 80, 117, 139-141, 144
 

insects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136 
 

Integrated Risk Information System (see IRIS) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 196 
 

intermediate oral exposure ......................................................................... 133, 141
 

International Agency for Research on Cancer (see IARC) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5, 191, 196
 

IRIS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85, 131, 136, 191, 194, 196
 

kidney disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5, 6 
 

kidney effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20, 37, 77, 78, 133, 144
 

LD50 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50, 72 
 

leukemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48, 143 
 

liver . . . . . . . . . . . . . . . . . . . . . . . . . . . 5, 6, 8, 12, 13, 18, 19, 23, 37, 40, 41, 48, 49, 74-76, 84, 85, 88, 89, 93, 94, 97-101, 106, 

109-112, 116, 118, 119, 121, 122, 124, 125, 131-133, 136, 137, 144, 145, 147, 148, 150, 191
 

lung . . . . . . . . 5, 8, 12, 17, 37, 38, 48, 73, 84, 88, 89, 94, 97-99, 101, 106, 109, 111, 112, 119, 125, 126, 135-137, 145, 147, 150
 

lymph . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80 
 

lymphatic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48, 143 
 

lymphoreticular effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14, 44, 79, 87 
 

mass spectrometry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 187, 190
 

metabolites . . . . . . . . . . . . . . . . . . . 17, 49, 94, 95, 101, 103-107, 109, 112, 113, 117-121, 123, 127, 128, 135, 146, 149, 181, 189
 

milk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6, 8, 11, 95, 97, 98, 100, 107, 118, 120, 127, 128, 144-146, 150, 160, 171, 175
 

Minimal Risk Level (see MRL) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 
 

monkey . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40 
 

MRL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12, 13, 18-20, 22, 41, 77, 132-134, 140, 141, 191
 

musculoskeletal effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40, 75 
 

NAS/NRC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119 
 

National Priorities List (see NPL) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1, 12, 160 
 

National Toxicology Program (see NTP) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129, 176, 188
 

neoplastic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74, 123 
 

neurobehavioral . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114 
 

neurodevelopmental . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139 
 

neurotransmitter . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81 
 

NIOSH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9, 153, 160, 172, 173, 176, 179, 181, 183, 185, 189, 192, 195, 196
 

NOAEL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15, 18, 19, 21, 38, 41, 43, 45-48, 72, 75, 78-83, 133, 134, 191
 

NOES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 172, 173
 

NPL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1, 12, 15, 83, 139, 142, 149, 160-163
 

NTP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72-82, 102, 118, 129, 133, 136, 138, 140, 142, 146, 147, 150, 176, 177, 188, 191
 

Occupational Safety and Health Administration (see OSHA) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8, 196 
 

ocean . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167 
 

ocular effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43, 78, 79, 86, 131 
 

odds ratio (see OR) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48, 83, 139 
 

OR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-23, 38-49, 72-84, 86-88, 91, 94-98, 100, 101, 103, 105-110, 113-120, 122-129, 

131-134, 136, 138-151, 156, 158-160, 162-168, 171-173, 175-177, 179-181, 183-185, 189, 191, 193
 

OSHA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8, 9, 192, 196
 

partition coefficients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154 
 

PBPD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108 
 

PBPK . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108-110, 145, 151
 

pharmacodynamic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108 
 

pharmacokinetic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101, 108-111
 

photolysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11, 160, 163, 165, 166
 

precipitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163 
 

produce . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6, 13-15, 38-40, 46, 72, 80, 81, 91, 109, 112, 113, 121-123, 128, 132, 135, 140, 158
 
1,2-DICHLOROETHANE D-3 

APPENDIX D 

reference dose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 196 
 

regulations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8, 9, 191-193, 195, 196
 

renal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12, 13, 19, 37, 41, 42, 49, 76-78, 86, 112, 116, 121, 122, 126, 127, 133, 148
 

renal effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13, 41, 42, 76, 77, 122 
 

reportable quantity ............................................................................... 193, 194
 

RfD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191, 194, 196
 

salmon . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93 
 

sediment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163-167, 171, 178, 183, 186-189
 

serum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13, 40, 41, 77, 95, 111, 122, 127, 144
 

sheep . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14, 19, 80, 116, 117, 122, 140
 

sheep red blood cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14, 140 
 

soil . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-4, 9, 11, 12, 159, 160, 163-167, 171, 176-178, 180, 185, 186, 188
 

solubility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74, 97, 154 
 

Superfund . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 166 
 

time-weighted average (see TWA) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 196 
 

toxicokinetic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19-21, 134, 145, 146
 

Toxics Release Inventory (see TRI) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156, 162
 

TRI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156, 162, 163, 177
 

triglycerides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75 
 

tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5, 17, 48, 49, 84, 86, 87, 113, 123, 134, 135, 143, 147
 

TWA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 192, 196
 

urine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4, 8, 94, 96, 104-108, 110, 120, 123, 127, 144, 160, 173, 178, 181-183, 189
 

vapor phase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156 
 

vapor pressure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95, 111, 154
 

vegetables . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171, 193
 

volatility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 176 
 

volatilization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11, 76, 132, 163-165, 169, 173
 

WHO . . . . . . . . . . . . . . . . . . . . . . . 4-6, 12-14, 23, 37, 39, 41, 43, 45, 46, 48-50, 72-77, 79, 80, 98, 109, 115-117, 125, 126, 129, 

131, 133, 141, 147-150, 168, 171, 175, 176, 192, 196 

World Health Organization (see WHO) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 196