## DRAFT

TOXICOLOGICAL PROFILE FOR 1,1

- DICHLOROETHANE

PUBLIC COMMENT PERIOD ENDS September 30, 2013

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES

Public Health Service Agency for Toxic Substances and Disease Registry

April 2013ii 1,1

- DICHLOROETHANE



### DISCLAIMER

Use of trade names is for identification only and does not imply endorsement by the Agency for Toxic Substances and Disease Registry, the Public Health Service, or the U.S. Department of Health and Human

Services.

This information is distri buted solely for the purpose of pre dissemination public comment under applicable information quality guidelines. It has not been formally disseminated by the Agency for Toxic Substances and Disease Registry. It does not represent and should not be const rued to represent any agency determination or policy.

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### UPDATE STATEMENT

A Toxicological Profile for 1,1-Dichloroethane was released in 1990. This present edition supersedes any previously released draft or final profile.

Toxicological profiles are r evised and republished as necessary. For information regarding the update status of previously released profiles, contact ATSDR at:

Agency for Toxic Substances and Disease Registry Division of Toxicology and Human Health Sciences Environmental Toxicolog y Branch

1600 Clifton Road NE Mailstop F-57 Atlanta, Georgia 30333

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### FOREWORD

This toxicological profile is prepared in accordance with guidelines developed by the Agency for Toxic Substances and Disease Registry (ATSDR) and the Environmental Protection Agency (EPA). The original guidelines were published in the Federal Register on April 17, 1987. Each profile will be revised and republished as necessary.

The ATSDR toxicological profile succinctly characterizes the toxicologic and adverse health effects information for these toxic substances described therein. Each peer-reviewed profile identifies and reviews the key literature that describes a substance's toxicologic properties. Other pertinent literature is also presented, but is described in less detail than the key studies. The profile is not intended to be an exhaustive document; however, more comprehensive sources of specialty information are referenced.

The focus of the profiles is on health and toxicologic information; therefore, each toxicological profile begins with a public health statement that describes, in nontechnical language, a substance's relevant toxicological properties. Following the public health statement is information concerning levels of significant human exposure and, where known, significant health effects. The adequacy of information to determine a substance's health effects is described in a health effects summary. Data needs that are of significance to protection of public health are identified by ATSDR and EPA.

Each profile includes the following:

(A) The examination, summary, and interpretation of available toxicologic information and epidemiologic evaluations on a toxic substance to ascertain the levels of significant human exposure for the substance and the associated acute, subacute, and chronic health effects;

(B) A determination of whether adequate information on the health effects of each substance is available or in the process of development to determine levels of exposure that present a significant risk to human health of acute, subacute, and chronic health effects; and

( C) Where appropriate, identification of toxicologic testing needed to identify the types or levels of exposure that may present significant risk of adverse health effects in humans.

The principal audiences for the toxicological profiles are health professionals at the Federal, State, and local levels; interested private sector organizations and groups; and members of the public. We plan to revise these documents in response to public comments and as additional data become available. Therefore, we encourage comments that will make the toxicological profile series of the greatest use.

Electronic comments may be submitted via: www.regulations.gov. Follow the on-line instructions for submitting comments.

Written comments may also be sent to: Agency for Toxic Substances and Disease Registry Division of Toxicology and Human Health Sciences Environmental Toxicology Branch

Regular Mailing Address: Physical Mailing Address:

1600 Clifton Road, N.E. 4770 Buford Highway Mail Stop F-57 Building 106, 3 rd floor, MS F-57 Atlanta, Georgia 30333 Chamblee, Georgia 30341

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The toxicological profiles are developed under the Comprehensive Environmental Response, Compensation, and Liability Act of 1980, as amended (CERCLA or Superfund). CERCLA section 104(i)(1) directs the Administrator of ATSDR to “...effectuate and implement the health related authorities” of the statute. This includes the preparation of 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. Section 104(i)(3) of CERCLA, as amended, directs the Administrator of ATSDR to prepare a toxicological profile for each substance on the list. In addition, ATSDR has the authority to prepare toxicological profiles for

substances not found at sites on the National Priorities List, in an effort to “...establi sh and maintain inventory of literature, research, and studies on the health effects of toxic substances” under CERCLA Section 104(i)(1)(B), to respond to requests for consultation under section 104(i)(4), and as otherwise necessary to support the site-specific response actions conducted by ATSDR.

This profile reflects ATSDR ’ s assessment of all relevant toxicologic testing and information that has been peer-reviewed. Staffs of the Centers for Disease Control and Prevention and other Federal

scientists ha ve also reviewed the profile. In addition, this profile has been peer-reviewed by a nongovernmental panel and is being made available for public review. Final responsibility for the contents and views expressed in this toxicological profile resides with ATSDR.

Robin M. Ikeda, MD, MPH Acting Assistant Administrator Agency for Toxic Substances and Disease Registry

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### QUICK REFERENCE FOR HEALTH CARE PROVIDERS

Toxicological Profiles are a unique compilation of toxicological information on a given hazardous substance. Each prof ile 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 fol lowing 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 hazar dous 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 Relev ance 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 necessaril y observed in the clinical setting. Please refer to the Public Health Statement to identify general health effects observed following exposure.

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

issues:

Section 1.6 How Can (Chemical X) Affect Children?

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

Section 3.7 Children’s Susceptibility

Section 6.6 Exposures of Children

Other Sections of Interest:

Section 3.8 Biomarkers of Exposure and Effect

Section 3.11 Methods for Reducing Toxic Effects

ATSDR Information Center

Phone: 1-800- CDC

- INFO (800 -232-4636) or 1-888-232-6348 (TTY) Fax: (770) 488-4178

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

Th e 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.

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Man aging 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 respond ers and hospital emergency department personnel in planning for incidents that involve hazardous materials. Volume III— Medical Management Guidelines for Acute Chemical Exposure s— is a guide for health care professionals treating patients exposed to hazardo us 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 d isability 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 Occupat ional 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 ch emical, 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 Environ mental Clinics (AOEC) has developed a network of clinics in the United States to provide expertise in occupational and environmental issues. Contact: AOEC, 1010 Vermont Avenue, NW, #513, Washington, DC 20005 • Phone: 202-347-4976

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

The American College of Occupational and Environmental Medicine (ACOEM) is an association of physicians and other health care providers specializing in the field of occupational and environmental medicine. Contact: ACOEM, 25 Northwest Point Boulevard, Suite 700, Elk Grove Village, IL 60007-1030 • Phone: 847-818-1800 • FAX: 847-818-9266.

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### CONTRIBUTORS

CHEMICAL MANAGER(S)/AUTHOR(S):

Malcolm Williams, DVM, Ph.D. Annette Ashizawa, Ph.D.

G. Daniel Todd, Ph.D. Eugene Demchuk, Ph.D. ATSDR, Division of Toxicology and Human Health Sciences, Atlanta, GA

Lisa Ingerman, Ph.D., DABT

Chris tina Coley , B.S. Mario Citra, Ph.D.

SRC

, Inc.

, 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 Environmental Tox icology Branch reviews data needs sections to assure consistency across profiles and adherence to instructions in the Guidance.

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

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### PEER REVIEW

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

members:

1. Gary Stoner, Ph.D., Department of Medicine, Division of Hematology and Oncology, Medical College of Wisconsin

, Milwaukee, Wisconsin;

2. G.A. Shakeel Ansari, Ph.D., Department of Human Biological Chemistry & Genetics and Pathology

, University of Texas Medical Branch

, Galveston T exas;

3. Hermann Bolt, Ph.D., Institut für Arbeitsphysiologie an der Universität Dortmund (IfADo),

Leibniz R esearch Centre for Working Environment and Human Factors, Dortmund, Germany.

These experts collectively have knowledge of 1,1- 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.

The citation of the peer review panel should not be understood to imply its approval of the profile's final content. The responsi bility for the content of this profile lies with the ATSDR.

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### CONTENTS

DISCLAIMER

................................................................................................ .............................................. ii

UPDATE STATE MENT

............................................................................................................................. iii

FOREWORD

................................................................................................ ................................................ v QUICK REFERENCE FOR HEALTH CARE PROVIDERS

.................................................................... vii

CONTRIBUTORS

................................................................................................ ....................................... ix

PEER REVIEW

................................................................................................ ........................................... xi

CONTENTS

................................................................................................ ............................................... xiii

LIST OF FIGURES

................................................................................................ .................................. xvii

LIST OF TABLES

................................................................................................ ..................................... xix

1. PUBLIC HEALTH STATEMENT FOR 1,1

- DICHLOROETHANE

..................................................... 1

2. RELEVANCE TO PUBLIC HEALTH

................................................................................................... 9

2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO 1,1

- DICHLOROETHANE IN

THE UNITED STATES

................................................................................................................. 9

2.2 SUMMARY OF HEALTH EFFECTS

........................................................................................... 9

2.3 MINIMAL RISK LEVELS (MRLs)

............................................................................................ 13

3. HEALTH EFFECTS

.............................................................................................................................. 15

3.1 INTRODUCTION

........................................................................................................................ 15

3.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE

..................................... 15

3.2.1 In halation Exposure

.............................................................................................................. 16

3.2.1.1 Death

.............................................................................................................................. 16

3.2.1.2 Systemic Effects

............................................................................................................. 21

3.2.1.3 Immunological and Lymphoreticular Effects

................................................................ 22

3.2.1.4 Neurological Effects

...................................................................................................... 22

3.2.1.5 Reproductive Effects

...................................................................................................... 22

3.2.1.6 Developmental Effects

................................................................................................... 22

3.2.1.7 Cancer

............................................................................................................................ 23

3.2.2 Oral Exposure

........................................................................................................................ 23

3.2.2.1 Death

.............................................................................................................................. 23

3.2.2.2 Systemic Effects

............................................................................................................. 28

3.2.2.3 Immunological and Lymphoreticular Effects

................................................................ 29

3.2.2.4 Neurological Effects

...................................................................................................... 29

3.2.2.5 Reproductive Effects

...................................................................................................... 29

3.2.2.6 Developmental Effects

................................................................................................... 29

3.2.2.7 Cancer

............................................................................................................................ 30

3.2.3 Derm al Exposure

................................................................................................................... 31

3.2.3.1 Death

.............................................................................................................................. 31

3.2.3.2 Systemic Effects

............................................................................................................. 31

3.2.3.3 Immunological and Lymphoreticular Effects

................................................................ 31

3.2.3.4 Neurological Effects

...................................................................................................... 31

3.2.3.5 Reproductive Effects

...................................................................................................... 31

3.2.3.6 Developmental Effects

................................................................................................... 31

3.2.3.7 Cancer

............................................................................................................................ 31

3.3 GENOTOXI CITY

........................................................................................................................ 32

3.4 TOXICOKINETICS

..................................................................................................................... 34

3.4.1 Absorption

............................................................................................................................. 34

3.4.1.1 Inhalation Exposure

....................................................................................................... 34

***DRAFT FOR PUBLIC COMMENT***3.4.1.2 Oral Exposure

................................................................................................................ 34

3.4.1.3 Dermal Exposure

........................................................................................................... 35

3.4.2 Distribution

........................................................................................................................... 35

3.4.2.1 Inhalation Exposure

....................................................................................................... 35

3.4.2.2 Oral Exposure

................................................................................................................ 35

3.4.2.3 Dermal Exposure

........................................................................................................... 35

3.4.2.4 Other Routes of Exposure

.............................................................................................. 36

3.4.3 Metabolism

............................................................................................................................ 36

3.4.4 Elimination and Excretion

..................................................................................................... 40

3.4.4.1 Inhalation Exposure

....................................................................................................... 40

3.4.4.2 Oral Exposure

................................................................................................................ 40

3.4.4.3 Dermal Exposure

........................................................................................................... 40

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

............. 40

3.5 MECHANISMS OF ACTION

..................................................................................................... 43

3.5.1 Pharmacokinetic Mechanisms

............................................................................................... 43

3.5.2 Mechanisms of Toxicity

........................................................................................................ 43

3.5.3 Animal

- to -Human Extrapolations

......................................................................................... 43

3.6 TOXICITIES MEDIATED THROUGH T HE NEUROENDOCRINE AXIS

............................. 43

3.7 CHILDREN’S SUSCEPTIBILITY

.............................................................................................. 44

3.8 BIOMARKERS OF EXPOSURE AND EFFECT

....................................................................... 46

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

.......................... 48

3.8.2 Biomarkers Used to Characterize Effects Caused by 1,1

- Dichlo roethane

............................ 48

3.9 INTERACTIONS WITH OTHER CHEMICALS

....................................................................... 48

3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE

.................................................. 48

3.11 METHODS FOR REDUCING TOXIC EFFECTS

...................................................................... 49

3.11.1 Reducing Peak Absorption Following Exposure

............................................................... 49

3.11.2 Reducing Body Burden

..................................................................................................... 49

3.11.3 Interfering w ith the Mechanism of Action for Toxic Effects

............................................ 49

3.12 ADEQUACY OF THE DATABASE

.......................................................................................... 50

3.12.1 Existing Information on Health Effects of 1,1- Dichloroethane

......................................... 50

3.12.2 Identification of Data Needs

.............................................................................................. 52

3.12.3 Ongoing Studies

................................................................................................................ 57

4. CHEMICAL AND PHYSICAL INFORMATION

................................................................................ 59

4.1 CHEMICAL IDENTITY

.............................................................................................................. 59

4.2 PHYSICAL AND CHEMICAL PROPERTIES

........................................................................... 59

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

............................................................ 63

5.1 PRODUCTION

............................................................................................................................ 63

5.2 IMPORT/EXPORT

...................................................................................................................... 65

5.3 U SE

................................................................................................ .............................................. 65

5.4 DISPOSAL

................................................................................................ ................................... 65

6. POTENTIAL FOR HUMAN EXPOSURE

........................................................................................... 67

6.1 OVERVIEW

................................................................................................ ................................. 67

6.2 RELEASES TO THE ENVIRONMENT

..................................................................................... 67

6.2.1 Air

................................................................................................ ......................................... 70

6.2.2 Water

................................................................................................ ..................................... 72

6.2.3 Soil

................................................................................................ ........................................ 72

6.3 ENVIRONMENTAL FATE

........................................................................................................ 73

6.3.1 Transport and Partitioning

..................................................................................................... 73 xiv 1,1

- DICHLOROETHANE

***DRAFT FOR PUBLIC COMMENT***6.3.2 Transformation and Degradation

.......................................................................................... 75

6.3.2.1 Air

................................................................................................ .................................. 75

6.3.2.2 Water

.............................................................................................................................. 75

6.3.2.3 Sediment and Soil

.......................................................................................................... 76

6.4 LEVELS MONITORED OR ESTIMATED IN THE EN VIRONMENT

.................................... 76

6.4.1 Air

................................................................................................ ......................................... 76

6.4.2 Water

................................................................................................ ..................................... 78

6.4.3 Sediment an d Soil

................................................................................................................. 80

6.4.4 Other Environmental Media

.................................................................................................. 80

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE

.......................................... 81

6.6 EXPOSURES OF CHILDREN

.................................................................................................... 83

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES

................................................ 83

6.8 A DEQUACY OF THE DATABASE

.......................................................................................... 83

6.8.1 Identification of Data Needs

................................................................................................. 84

6.8.2 Ongoing Studies

.................................................................................................................... 87

7. ANALYTICAL METHODS

.................................................................................................................. 89

7.1 BIOLOGICAL MATERIALS

...................................................................................................... 89

7.2 ENVIRONMENTAL SAMPLES

................................................................................................ 95

7.3 ADEQUACY OF THE DATABASE

.......................................................................................... 98

7.3.1 Identification of Data Needs

................................................................................................. 98

7.3.2 Ongoing Studies

.................................................................................................................... 99

8. REGULATIONS, ADVISORIES, AND GUIDELINES

..................................................................... 101

9. REFERENCES

................................................................................................ .................................... 105

10. GLOSSARY

................................................................................................ ...................................... 129

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 xv 1,1

- DICHLOROETHANE

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### LIST OF FIGURES

2-1. Health Effects for Following I nhalation Exposure to 1,1-Dichloroethane

......................................... 11

2-2. Health Effects for Following Oral Exposure to 1,1-Dichloroethane

.................................................. 12

3-1. Levels of Significant Exposure to 1,1-Dichloroethane

– Inhalation

................................................... 19

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

– Oral

............................................................ 26

3-3. Proposed Metabolic Scheme for 1,1-Dichloroethane

......................................................................... 39

3-4. Conceptual Representation of a Physiologically Based Phar macokinetic (PBPK) Model for a Hypothetical Chemical Substance

...................................................................................................... 42

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

.......................................................... 51

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

..................................................... 68 xvii 1,1

- DICHLOROETHANE

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### LIST OF TABLES

3-1. Levels of Significant Exposure for 1,1-Dichloroethane – I nhalation

................................................. 17

3-2. Levels of Significant Exposure for 1,1-Dichloroethane

– Oral

.......................................................... 24

3-3. Genotoxicity of 1,1- Dichloroethane In Vitro

...................................................................................... 33

3-4. Production of Metabolites from 1,1- Dichloroethane with Hepati c Microsomes from

Phenobarb ital -Induced Rats

............................................................................................................... 38

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

........................................................................................... 60

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

- Dichloroethane

.................................................................. 61

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

.............................................................. 64

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

...... 71

7-1. Analytical Methods for Determining 1,1-Dichlor oethane in Biological Materials

............................ 90

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

....................... 91

8-1. Regulations, Advisories, and Guidelines Applicable to 1,1- Dichlor oethane

................................... 102 xix 1,1

- DICHLOROETHANE

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## 1. PUBLIC HEALTH STATEMENT FOR 1,1-DICHLOROETHANE

Overview

We define a public health statement and show how it can help you learn about 1,1-dichloroethane.

Introduction A public health statement summarizes information about a hazardous substance. The information is taken from a toxicological profile developed by ATSDR’s Division of Toxicology and Human Health Sciences (DTHHS)

. A toxicological profile is a thorough review of a hazardous substance.

This toxicological profile examines 1,1 -dichloroethane. This public health

statement summarizes the D THHS ’s findings on 1,1-diochloroethane, describes the effects of exposure to it, and describes what you can do to limit

that ex posure.

1,1

- Dichloroethane

at hazardous waste The U.S. Environmental Protection Agency (EPA) identifies the most serious

hazardous waste sites in the nation. U.S. EPA then includes these sites the

sites National Priorities List (NPL) and targets them fo r federal clean

- up activities. U.S. EPA has found 1,1- dichloroethane in at least 673 of the 1,69 9 current or

former NPL sites.

The total number of NPL sites evaluated for 1,1-dichloroethane is not known.
However, the possibility remains that as more sit es are evaluated, the number of sites at which 1,1-dichloroethane is found may increase. This information is important; these future sites may be sources of exposure, and exposure to 1,1

- dichloroethane may be harmful.

Why a 1,1- dichloroethane When a contaminant 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.

release ca n be

harmful However, such a release doesn’t always lead to exposure. You can only be exposed to a contaminant when you come in contact with it. That contact

— and therefore that exposure—can occur when you breathe, eat, or drink the contaminant, or when it touches your skin.

Even if you’re exposed to 1,1-dichloroethane, you might not be harmed. Whether you are harmed will depend on such factors as the dose (how much), the duration (how long), and how you happen to contact it. Harm might also depend on whether you’ve been exposed to any other chemicals, as well as your age, sex, diet, family traits, lifesty le, and state of health.

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- DICHLOROETHANE

1. PUBLIC HEALTH STATEMENT



## A Closer Look at 1,1- Dichloroethane

Overview

This section describes 1,1- dichloroethane in detail and how you can be exposed to it.

What is 1,1

- Dichloroethane is a colorless oily liquid with a chloroform

1,1- dichloroethane? like odor.

How is 1,1

- Dichloroethane is a chemical used mostly as an intermediate in the
1,1- dichloroethane manufacture of 1,1,1-trichloroethane, and to a lesser extent, vinyl chloride and

used? high vacuum rubber

.

Where is 1,1

- di

- 1,1

- Dichloroethane can be released into the air, water, and soil at

chloroethane places where it is produced or used as a solvent.

found?

Possible Sources Outcome

Air: Levels of 1,1

- dichloroethane in air samples have been measured at concentrations ranging from parts per tril lion to parts per million, depending upon the location

. In the air, 1,1

- dichloroethane is slow to break down and has the potential for long- range transport.

Water: 1,1

- Dichloroethane is infrequently detected in drinking water. Analyses of 13,347 Calif ornia groundwater sources of drinking water found 1,1- dichloroethane in 68 samples, ranging from 0.51 to 30 parts per billion (ppb )

. 1,1

- Dichloroethane is not expected to rapidly break down in water. It can evaporate from the water into the air

.

Soil: Very little information was

found on the ambient concentrations of 1,1-dichloroethane in soil, or on the current disposal of waste products containing the compound in

landfills. 1,1

- Dichloroethane released to land surfaces in spills would rapidly

volati lize to the atmosphere, but 1,1-dichloroethane remaining on soil

surfaces would be available for transport into groundwater, since the compound does not bind to soil particulates unless the organic content of the soil is high.

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- DICHLOROETHANE

1. PUBLIC HEALTH STATEMENT

Other Media: Little infor mation

was found on the levels of
1,1- dichloroethane in other media. In a survey of 234 table ready foods evaluated for the presence of volatile organic compounds (VOC s), 1,1-dichloroethane was not found in any of the samples . It was detected in three

p eanut butter samples at levels of 1.1, 1.9, and 3.7 micro grams per kilogram (μg/kg); however, the compound was

not found in several other foods that were analyzed

.



## How 1,1-Dichloroethane Can Affect Your Health

Overview

This section looks at how 1,1-dichloroethane enters your body and potential 1,1-dichloroethane health

effects found in human and animal studies.

How 1,1

- dichloro

- 1, 1

- Dichloroethane can enter your body from the air, water or consumer

ethane products.

Possible Sources Possible Exposure Pathway

Air If you breathe air containing 1,1-dichloroethane, it will enter your body through your lungs

. Water 1,1

- Dichloroethane in your drinking water will enter your body through the digestive tract

.

How 1,1

- dichloro

- 1,1

- Dichloroethane leaves your body in the breath or is broken down into other ethane leaves your chemicals and these chemicals leave your body in the breath or in the urine

. bod y

Introduction to 1,1- dichloroethane

health effects The health effects of 1,1

- dichloroethane depe nds on how much 1,1

- dichloro

ethane you are exposed to and the length of that exposure. Environmental monitoring data are limited. However, they do suggest that any 1,1-dichloroethane levels the public might encounter through contact, through air, water , or soil are generally much lower than animal

- study levels.

Effects in humans No information is available in humans on the health effects associated with exposure to 1,1-dichloroethane.

***DRAFT FOR PUBLIC COMMENT***4 1,1

- DICHLOROETHANE

1. PUBLIC HEALTH STATEMENT

Long

- term exposure effects Kidney effects have been observed i n cats exposed to 1,1

- dichloroethane in air for long periods . However, kidney effects have not been observed in other animal species following long

- term inhalation or oral exposure

.

1,1

- Dichloroethane

and cancer A study in rats and mice found sugges tive evidence that 1,1

- dichloroethane may cause cancer. However, the study had several flaws and the results are not conclusive. Another long- term study in mic e drinking water containing 1,1

- dichloroethane did not find cancer.

Some cancer findings b y government and other agencies • The U.S. Department of Health and Human Services (HHS) and The International Agency for Research on Cancer (IARC) have not evaluated the carcinogenic potential of 1,1 -dichloroethane.

• The U.S. EPA has determined that 1,1-dichloroethane is a possible human carcinogen

.

See Chapters 2 and 3 for more information on 1,1

- dichloroethane health effects.



## Children and 1,1-Dichloroethane

Overview

This section discusses potential health effects of 1,1 -dichloroethane exposure in humans from when they’re first conceived to 18 years of age, and how you might protect against such effects.

Exposure effects in No data describe the effects of exposure to 1,1

- dichloroethane on children or

children young animals. Although we think that chil dren would likely show the same health effects as adults, we don’t know whether children are more susceptible than are adults to 1,1

- dichloroethane effects.

What about birth We don’t know whether 1,1

- dichloroethane can harm an unborn child. Min or defects? skeletal problems were observed in the fetuses of rats breathing 1,1 -dichloroethane; decreases in body weight were also observed in the mothers

.



## Medical Tests to Determine 1,1- Dichloroethane Exposure

Overview

We identify medical tests that can detec t whether 1,1-dichloroethane is in your body, and we recommend

safe toxic

- substance practices.

***DRAFT FOR PUBLIC COMMENT***5 1,1

- DICHLOROETHANE

1. PUBLIC HEALTH STATEMENT

1,1

- Dichloroethane

can be measured in 1,1

- D ichloroethane and its breakdown products (metabolites) can be measured

in blood and urine

. However, the detection of 1,1- dichoroethane or its

blood and urine metabolites cannot predict the kind of health effects that might develop from that exposure. Because 1,1- dichloroethane and its metabolites leave the body fairly rapidly, the tests need to be conducted within day s after exposure.

For more information on the different substances formed by 1,1-dichloroethane breakdown and on tests to detect these substances in the body, see Chapters 3

and 7.



## Federal Government Recommendations to Protect Human

Health

Overview

One way the federal government promotes public health is by regulating toxic substances or recommending ways to handle or to avoid toxic substances.

The federal
government regulates toxic

substances Regulations are enforceable by law. The U.S. EPA, the Occu pational Safety and

H ealth Administration (OSHA), and the Food and Drug Administration (FDA) are some federal agencies that have adopted toxic substances regulations.

The federal
government

recommends safe

toxic substance practices The Agency for Toxic S ubstances and Disease Registry (ATSDR) and the

N ational Institute for Occupational Safety and Health (NIOSH) have made recommendations about toxic substances. Unlike enforceable regulations, these recommendations are advisory only.

Toxic substance

regu lations Regulations and recommendations can be expressed as “not

- to

- exceed” levels ; that is, levels of a toxic substance in air, water, soil, or food that do not exceed a critical value usually based on levels that affect animals; levels are then adjusted to help protect humans. Sometimes these not

- to

- exceed levels differ among federal organizations. Different organizations use different exposure times (an 8-hour workday or a 24-hour day), different animal studies, or emphasize some factors over others, d epending on their mission.

Check for Recommendations and regulations are also updated periodically as more regulation updates information becomes available. For the most current information, check with the federal agency or organization that issued the regulation or recommendation.

***DRAFT FOR PUBLIC COMMENT***6 1,1

- DICHLOROETHANE

1. PUBLIC HEALTH STATEMENT

Some regulations and recommendations for 1,1

- dichloroethane include :

Federal Organization Regulation or Recommendation

U.S. EPA The U.S. EPA has included 1,1- dichloroethane as a priority

contaminan t in the drinking wate r

program

. Occupational Safety and Health

Administration (OSHA) OSHA set a legal limit of 100 ppm
1,1- dichloroethane in air averaged over

an 8

- hour work day

. NIOSH NIOSH recommends a limit of 100 ppm 1,1- dichloroethane in air averaged over

a 10

- hour work day

.



## Additional Information

Overview

Where to find more information about 1,1-dichloroethane.

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

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

Additional ATSDR can also tell you the location of occupational and environmental health

information clinics. These clinics specialize in recognizing, evaluating, and treating illnesses

from ATSDR th at result from exposure to hazardous substances.

Where to

obtain toxicological profile copies Toxicological profiles are also available online at www.atsdr.cdc.gov and on

CD

- ROM. Request a copy of the ATSDR ToxProfiles TM CD

- ROM by

• Calling the toll

- free information and technical assistance number at

1-800- CDCINFO (1 -800-232-4636),

• E- mailing cdcinfo@cdc.gov, or

• Writing to

Agency for Toxic Substances and Disease Registry Division of Toxicology and Human Health Sciences

1600 Clifton Road NE Mailstop F

- 57 Atlanta, GA 30333

Fax: 1

- 770

- 488

- 4178

***DRAFT FOR PUBLIC COMMENT***7 1,1

- DICHLOROETHANE

1. PUBLIC HEALTH STATEMENT

For

- profit organizations should request final toxicological profile copies from

National Technical Information Service (NTIS) 5285 Port Royal Road Springfield, VA 22161

Phone: 1

- 800

- 553

- 6847 or 1

- 703

- 60 5

- 6000

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

***DRAFT FOR PUBLIC COMMENT***8 1,1

- DICHLOROETHANE

1. PUBLIC HEALTH STATEMENT



### This page is intentionally blank.

***DRAFT FOR PUBLIC COMMENT***9 1,1

- DICHLOROETHANE



### 2. RELEVANCE TO PUBLIC HE ALTH

2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO 1,1

- DICHLOROETHANE IN

THE UNITED STATES

T he production and use of 1,1- dichloroethane as a solvent, cleaning agent, and degreaser, and in the

manufacture of 1,1,1-trichloroethane, vinyl chloride, and h igh vacuum rubber may result in its release to

the environment . Volatilization is expected to be high based on its vapor pressure and Henry’s Law

constant. Atmospheric photooxidation occurs slowly in the environment, as does biodegradation and

hydrolysis. 1,1- Dichloroethane has high mobility in soil and has the potential to leach from surface soils

into groundwater. The bioaccumulation potential of 1,1- dichloroethane is low.

Monitoring data indicate that the general population may be exposed to 1,1-dichloroethane via inhalation

for people living near source areas, ingestion of contaminated drinking water, and use of consumer

products such as paint removers, which may contain this compound. Ingestion of food sources

contaminated with 1,1 -dichloroethane is not an important exposure pathway.

A National Health and Nutrition Survey of the U.S. population in 2003–2004 screened for 1,1-dichloroethane in blood from 1,367 participants in the age range of 20–59 years old, about half females (n=679)

and half males (n=670). The portion of the data below the limit of detection (LOD) was too high to

provide valid results.

2.2 SUMMARY OF HEALTH EFFECTS

R elatively little information is available on the health effects of 1,1 -dichloroethane in humans or animals.

Chlorinated aliphatics as a class are known to cause central nervous system depression and respiratory

tract and dermal irritation when humans are exposed by inhalation to sufficiently high levels. In the past,

1,1- dichloroethane was used as an anesthe tic; however, this use was discontinued due to the risk of

cardiac arrhythmia induction in humans at anesthetic doses (approximately 26,000 ppm). A small number

of animal studies have examined the toxicity and carcinogenicity of 1,1- dichloroethane; these studies

have failed to conclusively identify the critical targets of toxicity. Nonneoplastic effects are limited to

renal toxicity in cats, maternal and fetal toxicity in rats, and alterations in body weight gain. Crystal

precipitations and obstruction in the renal tubule lumina and increases in serum urea and creatinine were

observed in cats exposed to 500 ppm for 13 weeks followed by a 13-week exposure to 1,000 ppm for

13 weeks. However, these effects were not observed in rats, guinea pigs, or rabbit s similarly exposed to

***DRAFT FOR PUBLIC COMMENT***10 1,1

- DICHLOROETHANE

2. RELEVANCE TO PUBLIC HEALTH

1,1-dichloroethane, and renal effects have not been observed following gavage administration of 764 or

950 mg/kg/day in rats or 2 ,885 or 3,331 mg/kg /day in mice 5 days/week for 78 weeks or in mice exposed

to 465 mg/kg/day 1,1-dichloroethane in drinking water for 52 weeks . Kidney effects have also been

observed in mice administered a lethal intraperitoneal injection of 1,1-dichloroethane ; the effects included

increased glucose and protein in the urine and tubular swelling. The tox icological significance of the

nephrotoxicity observed in cats and the mice with regard to human health is not known given the small

number of animals tested (cats), the lack of a nephrotoxic effect in other species and in other studies

where 1,1-dichloroethane was administered orally.

The liver is the only other organ that has been examined in multiple studies; no hepatic effects have been

reported following intermediate-duration inhalation exposure of rats, guinea pigs, rabbits, or cats,

intermediate -duration oral exposure of mice , or chronic -duration exposure of rats and mice. The

reproductive, immunotoxicity, and neurotoxicity of 1,1-dichloroethane has not been examined following

inhalation, oral, or dermal exposure. A single developmental toxicity study reported retarded fetal

development (delayed ossification of vertebrae) in rats at 6 ,000 ppm (7 hours/day on gestation days 6–

15); an 11% decrease in maternal body weight gain and a decrease in maternal food consumption were

also reported at this concentration. There is inconclusive evidence that 1,1 -dichloroethane may be

carcinogenic in rodents. A significant positive dose

- related trend was observed for the incidence of

hemangiosarcomas and mammary adenocarcinomas in female rats, hepatocellular carcinomas in male

mice, and endometrial stromal polyps in female mice. However, only the incidence of endometrial

stromal polyps in female mice was significantly increased over the corresponding control animals.

Limitations in this study, particularly the poor survival in both treated and control animals, preclude the

consideration of these results as conclusive evidence of carcinogenicity . A 52-week drinking water study,

testing much lower doses, did not find increases in the incidence of lung, live r, or kidney tumors in mice.

Based on the available carcinogenicity data for 1,1-dichloroethane and supporting data on 1,2-dichloroethane, the EPA has classified 1,1 -dichloroethane as a possible human carcinogen (group C). Neither the

Department of Health and Human Services nor the International Agency for Research on Cancer have

classified the carcinogenic potential of 1,1 -dichloro ethane.

An overview of these data is pr esented in Fig ures 2 -1 and 2-2

.

***DRAFT FOR PUBLIC COMMENT***

### Figure 2-1

. Health Effects for Following Inhalation Exposure to 1,1

- Dichloroethane

Dose ( ppm ) Effects in Animals

6 ,000

750 (TWA) Maternal and developm ental effects a

Renal effects in cats b ; no liver or kidney effects in rats, guinea pigs, or rabbits 11 1,1

- DICHLOROETHANE

2. RELEVANCE TO PUBLIC HEALTH

a 11% decrease in maternal body weight gain and increased incidence of fetuses with delayed

ossification

b Increased serum urea and creatinine levels, crystal precipitations and obstruction in tubule

lum ina and dilatation of proximal section of renal tubules

TWA = tim e

- weighted average

***DRAFT FOR PUBLIC COMMENT***

### Figure 2-2

. Health Effects for Following Oral Exposure to 1,1

- Dichloroethane

Dose (mg/kg/day) a Effects in Animals

2,061 (males); 2,379 (f emales)

546 (males); 679 (f emales)

401 ( males) Highest no

- effect level in mice following chronic exposure

Highest no

- effect level in rats following chronic exposure

Decreases in body weight gain following 5 week exposure

a Doses adjusted for intermittent exposure (5 days/week) 12 1,1

- DICHLOROETHANE

2. RELEVANCE TO PUBLIC HEALTH

***DRAFT FOR PUBLIC COMMENT***13 1,1

- DICHLOROETHANE

2. RELEVANCE TO PUBLIC HEALTH

2.3 MINIMAL RISK LEVELS (MRLs)

Inhalation MRLs

There are limited data to derive inhalation MRLs for 1,1 -dichloroethane; the da tabase consists of two

inhalation studies. Hofmann et al. (1971) examined the potential for 1,1-dichloroethane to induce liver

and/or kidney effects in rats, guinea pigs, rabbits, and cats exposed to 500 ppm 6 hours/day, 5 days/week

for 13 weeks followed by a second 13-week exposure period to 1, 000 ppm. No adverse effects were

observed in the rats, guinea pigs, or rabbits. In three of four cats, increases in serum urea and creatinine

levels and renal tubular effects (crystalline precip it ates, obstruction of lumina, and dilatation) were

observed at the end of the 26-week period. Tubular degeneration and periglomerular fibrosis were also

noted; however, it is not known if this was observed in all affected cats. In a developmental toxicity

study (Schwetz e t al. 1974), decreases in maternal body weight gain and decreases in maternal food

consumption were observed in rats exposed to 3,800 or 6, 000 ppm 1,1 -dichloroethane on gestation

days 6–15 (7 hours/day); the magnitude of the decrease in weight gain was 8 and 11%, respectively.

Increases in the incidence of fetuses with delayed ossification of sternebrae were also observed at

6,000 ppm. No other developmental effects, including alterations in fetal resorptions, fetal growth, or

incidences of gross or soft tissue anomalies, were observed.

These studies examined a limited number of end points and there is a great deal of uncertainty regarding

the primary targets of toxicity following inhalation exposure. The lowest adverse effect level that has

been identi fied is 750 ppm (time- weighted average) for renal effects in cats following a 26

- week exposure

(Hofmann et al. 1971). However, this effect has not been corroborated in other species following

inhalation (Hofmann et al. 1971) or oral (Klaunig et al. 1986; NCI 1977) exposure. Additionally, it is not

known if cats are a good model for 1,1-dichloroethane-induced crystal formation and tubular damage and

there is uncertainty regarding the threshold concentration for these renal effects due to the exposure

protocol, which involved increasing the exposure concentration mid-way through the study. Both

maternal and fetal growth retardation w ere observed at 6,000 ppm in an acute-duration study; however, it

is not known if systemic or neurological effects would occur at lower concentrations. 1,1-Dichloroethane

has anesthetic properties at fairly high concentrations (approximately 26,000 ppm) (Miller et al. 1965), a

concentration also associated with cardiac arrhythmias ( Reid and Muianga 2012 ). It is not known if

exposure to lower concentrations would also result in central nervous system depressive effects or

cardiotoxic effects because these end points have not been examined. Uncertainties associated with

***DRAFT FOR PUBLIC COMMENT***14 1,1

- DICHLOROETHANE

2. RELEVANCE TO PUBLIC HEALTH

identification of the most sensitive target and the associat ed concentration -response relationships,

precludes deriving inhalation MRLs for 1,1-dichloroethane.

Oral MRLs

Two studies have examined the oral toxicity of 1,1- dichloroethane following intermediate - or chronicduration exposure. No lung, liver, or kidn ey effects were observed in mice exposed to doses as high as

465 mg/kg/day 1,1-dichloroethane in drinking water for 52 weeks (Klaunig et al. 1986); no other potential

targets were examined. Similarly, no nonneoplastic effects were noted in major tissues a nd organs of rats

and mice administered 1,1-dichloroethane in corn oil 5 days/week for 78 weeks (NCI 1977). The highest

doses tested were 764 and 950 mg/kg /day, respectively, in male and female rats and 2

, 885 and

3,331 mg/kg/day , respectively, in male and female mice. A 6 -week study found decreases in body weight

gain (>16%) in male rats administered 562 mg/kg/day and female rats administered 1 ,780 mg/kg/day

1,1-dichloroethane 5 days/week in corn oil (NCI 1977). No additional information was reported

, an d the

cause of the decreased weight gain is not known. The chronic-duration rat study did not find significant

alterations in body weight gain at higher concentrations in the male rats. Thus, the oral studies have not

identified a target of toxicity, precluding the derivation of oral MRLs for 1,1-dichloroethane.

***DRAFT FOR PUBLIC COMMENT***15 1,1

- DICHLOROETHANE



### 3. HEALTH EFFECTS

3.1 INTRODUCTION

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

oth er interested individuals and groups with an overall perspective on the toxicology of

1,1-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 D ISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE

To h elp public health professio nals 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 se rious" 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" ef fects and "serious" effects is

considered to be important because it helps the users of the profiles to identify levels of exposure at which

major health effects start to appear. LOAELs or NOAELs should also help in determining whether or not

***DRAFT FOR PUBLIC COMMENT***16 1,1

- DICHLOROETHANE

3. HEALTH EFFECTS

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 t he 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 b elow 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.

3.2.1 Inhalation Exposure

Ve ry little informatio n is available regarding the health effects of 1,1 -dichloroethane following inhalation

exposure in humans or animals. 1,1- Dichloroethane was used in the past as an anesthetic at a pressure of

0.026 atm, which is approximately equivalent to a concentration of 105,000 mg/m 3 (26,000 ppm) (Miller

et al. 1965). This use was discontinued when it was discovered that this compound induced cardiac

arrhythmias at anesthetic doses ( Reid and Muianga 2012 ).

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

inhala tion exposure levels at varying time and exposure durations.

3.2.1.1 D eath

No s tudies were located regarding death in humans following inhalation exposure to 1,1-dichloroethane.

In a review paper, Smyth (1956) reported that no deaths were observed in rats exposed to 4,000 ppm for

8 hours, but an 8-hour exposure to 16,000 ppm was lethal. It has been reported in the early literature that

the lethal exposure level of 1,1- dichloroethane in mice was 17,500 ppm (Reid and Muianga 2012 ). These

values were reported in a secondary source and it is therefore impossible to assess their validity.

Subchronic intermittent exposure to 500 ppm of 1,1-dichloroethane for 13 weeks followed by 1,000 ppm

of 1,1-dichloroethane for an additional 13 weeks was not lethal to rats, rabbits, guinea pigs, or cats

(Hofmann et al. 1971).

The highest NOAEL values for death in each species and duration category are recorded in Table 3-1 and

plotte d in Figure 3-1

.

***DRAFT FOR PUBLIC COMMENT***258600025730006800272750750750274750750750273750750750Table 3-1 Levels of Significant Exposure to 1,1-dichloroethane - InhalationaKey toFigureSpecies(Strain)Exposure/Duration/Frequency(Route)ACUTE EXPOSURESystemic1Rat(SpragueDawley)7 hr/d10 dDevelopmental2Rat(SpragueDawley)7 hr/dGd 6-15SystemHepaticNOAEL(ppm)6000 F3000 FLOAELLess Serious(ppm)Serious(ppm)6800 F (Increased incidence ofdelayed ossification)ReferenceChemical FormSchwetz et al. 1974Schwetz et al. 1974CommentsINTERMEDIATE EXPOSURESystemic3Rat(SpragueDawley)6 hr/d5 d/wk26 wkHepatic 750Hofmann et al. 19711,1-DCERenal 750Bd Wt 7504Gn Pig(FirbrightWhite)6 hr/d5 d/wk26 wkHepatic 750Hofmann et al. 19711,1-DCERenal 750Bd Wt 7505Rabbit(Brunte)6 hr/d5 d/wk26 wkHepatic 750Hofmann et al. 19711,1-DCERenal 750Bd Wt 750275750750750Table 3-1 Levels of Significant Exposure to 1,1-dichloroethane - Inhalation(continued)aKey toFigureSpecies(Strain)Exposure/Duration/Frequency(Route)SystemNOAEL(ppm)Less Serious(ppm)LOAELSerious(ppm)ReferenceChemical FormComments6Cat(NS)6 hr/d5 d/wk26 wkHepatic750Hofmann et al. 19711,1-DCERenal750 (crystal precipitation andobstruction in tubulelumina)Bd Wt750a The number corresponds to entries in Figure 3-1.Bd Wt = body weight; d = day(s); F = Female; Gd = gestational day; Gn pig = guinea pig; hr = hour(s); LOAEL = lowest-observed-adverse-effect level; NOAEL =no-observed-adverse-effect level; NS = not specified; wk = week(s)Hepatic Developmental

10000 

### Figure 3-1 Levels of Significant Exposure to 1,1-Dichloroethane - Inhalation

Acute (≤14 days)

Sy stem ic

ppm

2r

1r

2r

Cancer Effect Level-Animals LOAEL, More Serious-Animals LOAEL, Less Serious-Animals NOAEL - Animals Cancer Effect Level-Humans LOAEL, More Serious-Humans LOAEL, Less Serious-Humans NOAEL - Humans LD50/LC50 Minimal Risk Level for effects other than Cancer r-Rat 1000Hepatic Renal Body Weight 

### Figure 3-1 Levels of Significant Exposure to 1,1-Dichloroethane - Inhalation (Continued)

Intermediate (15-364 days)

Systemic

ppm

100 1000

6c 4g 3r 5h 6c 4g 3r 5h 6c 4g 3r 5h

c-Cat
r-Rat h-Rabbit g-Guinea Pig Cancer Effect Level-Animals LOAEL, More Serious-Animals LOAEL, Less Serious-Animals NOAEL - Animals Cancer Effect Level-Humans LOAEL, More Serious-Humans LOAEL, Less Serious-Humans NOAEL - Humans LD50/LC50 Minimal Risk Level for effects other than Cancer21 1,1

- DICHLOROETHANE

3. HEALTH EFFECTS

3.2.1.2 Systemic Effects

No studies were located regarding respiratory, gastrointestinal, hematological, musculoskeletal, or

dermal/ocular effects in humans or animals following inhalation exposure to 1,1- dichloroethane.

Cardiovascular Effects. A cardiost imulatory effect resulting in arrhythmias prompted the

discontinuance of the use of 1,1- dichloroethane as an anesthetic in humans ( Reid and Muianga 2012).

This effect was noted at the relatively high dose used to induce anesthesia (0.026 atm, which is

approximately equivalent to 105,000 mg/m 3 , or 26,000 ppm) (Miller et al. 1965). No studies were located

regarding cardiovascular effects in animals following inhalation exposure to 1,1

- dichloroethane.

Hepatic Effects. No studies were located regarding he patic effects in humans following inhalation

exposure to 1,1 -dichloroethane. Rats, rabbits, guinea pigs, and cats experienced no change in serum

alanine aminotransferase or aspartate aminotransferase activity after intermittent 6

- hour inhalation

exposure to 500 ppm 1,1-dichloroethane for 13 weeks followed by 13 weeks of exposure 6 hours/day to

1,000 ppm 1,1-dichloroethane (Hofmann et al. 1971). Furthermore, no treatment-related histopathological lesions were noted in the livers of these animals after thi s 26

- week exposure regimen. Six days

after termination of a 10-day exposure to 6,000 ppm 1,1-dichloroethane (7 hours/day), a slight but

statistically significant increase in relative liver weight (26% higher than controls) was observed in female

Sprague-D awley rats (Schwetz et al. 1974). However, there was no increase in aspartate amino

transferase activity over control values, and no changes in the gross appearance of the liver were noted at

necropsy in these animals; the slight increase in liver weight was not considered adverse

.

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

exposure to 1,1

- dichloroethane. Renal injury was apparent in cats intermittently exposed 6 hours/day to

1,000 ppm 1,1-dichloroe thane for 13 weeks following 13 weeks of intermittent exposure to 500 ppm

1,1- dichloroethane (Hofmann et al. 1971). Serum urea and creatinine were increased in these animals.

One cat was so severely affected that it had to be removed from the study. His topathological lesions in

the kidney tubules (including crystalline precipitates and dilation) were noted in three of four cats at

necropsy ; renal tubular degenerations without preliminary lumen displacement and periglomerular

fibrosis and tubule destruction were also observed. The ill health of these animals was also manifest by a

progressive decrease in body weight. Rats, rabbits, and guinea pigs similarly exposed to 1,1-dichloroethane exhibited no adverse effects.

***DRAFT FOR PUBLIC COMMENT***22 1,1

- DICHLOROETHANE

3. HEALTH EFFECTS

3.2.1.3 Immunological and Lymphoreticular Effects

No studies were located regarding immunological effects in humans or animals after inhalation exposure

to 1,1-dichloroethane.

3.2.1.4 N eurological Effects

Si nce 1,1

- dichloroethane was once used as a gaseous anesthetic, it can be inferred that it causes central

nervous system depression upon acute exposure. No information is available on the long-term neurologic

effects of inhaled 1,1

- dichloroethane in humans.

No studies were located regarding neurologic effects in animals after inhalation exposure to 1,1-dichloroethane.

3.2.1.5 R eproductive Effects

No studies were located regarding developmental effects in humans or animals following inhalation

exposure to 1,1

- dichloroethane.

3.2.1.6 D evelopmental Effects

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

1,1-dichloroethane.

One study examined the developmental toxic potential of 1,1- dichloroet hane following inhalation

exposure. No alterations in litter size, fetal resorptions, fetal growth, or incidences of gross or soft tissue

anomalies were observed in the offspring of Sprague

- Dawley rats exposed to 3 ,800 or 6,000 ppm

7 hours/day on gestation days 6–15 (Schwetz et al. 1974). A significant increase in the incidence of

f etuses with delayed ossification of sternebrae was observed at 6,000 ppm. Maternal food consumption

and body weight were significantly reduced in the treated animals during the exposure period but returned

to normal by day 21 of gestation; on gestation da y 3, da ms in the 3,800 and 6, 000 ppm groups weighed

8 and 11% less than controls, respectively. No other adverse effects were noted in the dams. Based on

the observed effects, the LOAEL value for the developmental toxicity of 1,1- dichloroethane in rats was

6,000 ppm; the NOAEL was 3,800 ppm. These values are listed in Table 3-1 a nd plotted in Figure 3-1

.

***DRAFT FOR PUBLIC COMMENT***23 1,1

- DICHLOROETHANE

3. HEALTH EFFECTS

3.2.1.7 Cancer

No studies were located regarding cancer in humans or animals after inhalation exposure to 1,1-dichloroethane.

3.2.2 Oral Exposu re

Tw o studies were located that investigated the health effects associated with oral exposure to 1,1 -dichloroethane in rats and mice (Klaunig et al. 1986; NCI 1977). With the exception of body weight

depression observed in one subchronic range-finding study, neither one provided any conclusive evidence

of adverse toxic effects associated with oral exposure to 1,1-dichloroethane.

Table 3-2 and Figure 3- 2 describe the health effects observed in laboratory animals associated with oral

exposu re levels at varying time and exposure durations. No MRLs to humans for adverse effects (other

than cancer) were calculated for the oral route of exposure because of the limited database.

3.2.2.1 D eath

No s tudies were located regarding death in humans following o ral exposure to 1,1 -dichloroethane.

Secondary sources report the following oral LD 50 values in rats: 725 mg/kg (Lewis 2004) and 14.1 g/kg

( Archer 1978). Since these values were obtained from secondary sources, no details were available to

assess the qu ality of these data. Survival was poor in both treated and control rats and mice in the chronic

bioassay conducted by the National Cancer Institute (NCI 1977), but a significant dose- related trend for

mortality was noted in the male rats and mice. The de aths could not be attributed to cancer or any other

non- neoplastic lesions, although pneumonia was observed in a large percentage of the rats, and this was

thought to be related to the increased mortality (NCI 1977).

The highest NOAEL values and all relia ble LOAE L values for death in each species and duration

category are recorded in Table 3-2 and plotted in Figure 3-2

.

***DRAFT FOR PUBLIC COMMENT***2653160268562026456210002694654654654652672885Table 3-2 Levels of Significant Exposure to 1,1-dichloroethane - OralaKey toFigureSpecies(Strain)Exposure/Duration/Frequency(Route)INTERMEDIATE EXPOSUREDeath1Rat(OsborneMendel)5 d/wk6 wk(GO)SystemNOAEL(mg/kg/day)Less Serious(mg/kg/day)LOAELSerious(mg/kg/day)3160 F (2/5 rats died)ReferenceChemical FormNCI 19771,1-DCEComments2Mouse(B6C3F1)Systemic3Rat(OsborneMendel)5 d/wk6 wk(GO)5 d/wk6 wk(GO)Bd Wt562 M (16% decreased bodyweight gain)5620 (4/10 deaths)1000 M (29% decreased bodyweight gain)NCI 19771,1-DCENCI 19771,1-DCE4Mouse(B6C3F1)daily52 wk(W)Resp465 MKlaunig et al. 19861,1-DCEHepaticRenal465 M465 MBd Wt465 M5Mouse(B6C3F1)5 d/wk6 wk(GO)Bd Wt2885 MNCI 19771,1-DCE259764764764764764764764764764261288528852885288528852885288528852885Table 3-2 Levels of Significant Exposure to 1,1-dichloroethane - Oral(continued)Exposure/Duration/aKey to SpeciesFrequencyFigure (Strain)(Route)CHRONIC EXPOSURESystemic6Rat 5 d/wk78 wk(OsborneMendel)(GO)7Mouse5 d/wk78 wk(B6C3F1)(GO)SystemRespCardioHematoMusc/skelHepaticRenalEndocrDermalBd WtRespCardioGastroMusc/skelHepaticRenalEndocrDermalBd WtLOAELNOAEL(mg/kg/day)Less Serious(mg/kg/day)Serious(mg/kg/day)ReferenceChemical FormComments764 MNCI 19771,1-DCE764 M764 M764 M764 M764 M764 M764 M764 M2885 MNCI 19771,1-DCE2885 M2885 M2885 M2885 M2885 M2885 M2885 M2885 Ma The number corresponds to entries in Figure 3-2.Bd Wt = body weight; Cardio = cardiovascular; d = day(s); Endocr = endocrine; F = Female; Gastro = gastrointestinal; (GO) = gavage in oil; Hemato = hematological; hr = hour(s);LOAEL = lowest-observed-adverse-effect level; M = male; Musc/skel = musculoskeletal; NOAEL = no-observed-adverse-effect level;NS = not specified; Resp = respiratory; (W) =drinking water; wk = week(s)Death Respiratory Hepatic Renal Body Weight 

### Figure 3-2 Levels of Significant Exposure to 1,1-Dichloroethane - Oral

Intermediate (15-364 days)

Systemic

mg/kg/day

100 1000 10000

2m

1r

4m 4m 4m 4m 5m

3r

3r

r-Rat m-Mouse Cancer Effect Level-Animals LOAEL, More Serious-Animals LOAEL, Less Serious-Animals NOAEL - Animals Cancer Effect Level-Humans LOAEL, More Serious-Humans LOAEL, Less Serious-Humans NOAEL - Humans LD50/LC50 Minimal Risk Level for effects other than CancerRespiratory Cardiovascular Gastrointestinal Hematological Musculoskeletal Hepatic Endocrine Dermal Body Weight Renal 

### Figure 3-2 Levels of Significant Exposure to 1,1-Dichloroethane - Oral (Continued)

Chronic (≥365 days)

Systemic

mg/kg/day

100 1000 10000

7m

6r 7m

6r 7m

6r 7m

6r 7m

6r 7m

6r 7m

6r 7m

6r 7m

6r

r-Rat m-Mouse Cancer Effect Level-Animals LOAEL, More Serious-Animals LOAEL, Less Serious-Animals NOAEL - Animals Cancer Effect Level-Humans LOAEL, More Serious-Humans LOAEL, Less Serious-Humans NOAEL - Humans LD50/LC50 Minimal Risk Level for effects other than Cancer28 1,1

- DICHLOROETHANE

3. HEALTH EFFECTS

3.2.2.2 Systemic Effects

N o studies were located regarding systemic effects in humans following oral exposure to 1,1-dichloroethane.

There were no treatment

- related histopathological changes in the liver, kidneys, or other tissues of the rats

examined in the NCI (1977) study. Similarly, no histopathological alterations were noted in the liver,

kidneys, or lungs of m ale mice that ingested relatively high levels of 1,1 -dichloroethane in drinking water

(up to 2500 mg/L) for 52 weeks (Klaunig et al. 1986).

Respiratory Effects. No histological alterations were observed in the lungs of mice exposed to

465 mg/kg/day 1, 1-dichloroethane in drinking water for 52 weeks (Klaunig et al. 1986). Similarly, no

significant alterations in respiratory tract lesions were observed in rats or mice chronically exposed to

1,1-dichloroethane for 78 weeks (NCI 1977). The highest gavage doses were 764 and 950 mg/kg/day

(5 days/week) in male and female rats , respectively, and 2 ,885 and 3,331 mg/kg (5 days/week) in male

and female mice , respectively

.

Cardiovascular Effects. The NCI (1977) chronic-duration gavage study did not find signi ficant

alterations in the incidence of lesions in the cardiovascular system.

Gastrointestinal Effects. No gastrointestinal effects were reported in rats or mice administered

gavage doses of 1,1 -dichloroethane for 78 weeks (NCI 1977).

Hematological Eff ects. No histological alterations were observed in hematological tissues in rats or

mice chronically exposed to 1,1-dichloroethane (NCI 1977); however, the study did not examine the

potential for alterations in erythrocyte or leukocyte counts or hemoglo bin levels.

Musculoskeletal Effects. No musculoskeletal alterations were reported in the NCI (1977) chronic

study of rats and mice.

Hepatic Effects. No nonneoplastic alterations were observed in mice exposed to 465 mg/kg/day via

drinking water for 52 weeks (Klaunig et al. 1986) or in rats or mice administered 764/950 mg/kg/day or

***DRAFT FOR PUBLIC COMMENT***29 1,1

- DICHLOROETHANE

3. HEALTH EFFECTS

2,885/3,331 mg/kg/day 1,1- dichloroethane, respectively, via gavage 5 days/week for 78 weeks (NCI

1977).

Renal Effects. Intermediate -duration drinking exposure of mice (Klaunig et al. 1986) or chronic

gavage administration to rats and mice (NCI 1977) did not result in significant alteration in the occurrence

of renal lesions.

Endocrine Effects. No histological alterations in endocrine tissues were observed in rats or mice

chronically administered 1,1 -dichloroethane (NCI 1977).

Dermal Effects. No dermal effects were noted in rats or mice administered 1,1 -dichloroethane for

78 weeks (NCI 1977).

Ocular Effects. No eye damage was noted in rats or mice following c hronic administration of

1,1- dichloroethane (NCI 1977).

Body Weight Effects. Administration of doses as high as 562 mg/kg/day in male rats and

1,780 mg/kg /day in female rats 5 days/week for 6 weeks resulted in decreases in body weight gain

(≥16%) (NCI 1977); no alterations in body weight were observed in mice similarly exposed to doses as

high as 10,000 mg/kg /day (NCI 1977). This study did not find significant decreases in body weight gain

following 78 week s of exposure (5 days/week) to 764 and 950 mg/kg /day, respectively, in male and

female rats and 2,885 and 3,331 mg/kg /day, respectively, in male and female mice (NCI 1977).

Similarly, no alterations in body weight gain were observed in mice exposed to 465 mg/kg/day in

drinking water for 52 weeks (Klaunig et al. 1986).

No studies were located regarding the following health effects in humans or animals following oral

exposure to 1,1

- dichloroethane:

3.2.2.3 Immunological and Lymphoreticular Effects

3.2.2.4 Neurological Effects

3.2.2.5 Reproduct ive Effects

3.2.2.6 Developmental Effects

***DRAFT FOR PUBLIC COMMENT***30 1,1

- DICHLOROETHANE

3. HEALTH EFFECTS

3.2.2.7 Cancer

N o studies were located regarding carcinogenic effects in humans following oral exposure to

1,1-dichloroethane. The results of the bioassay conducted by NCI (1977) suggest carcinogenic effe cts

induced by 1,1- dichloroethane in rats and mice. A significant positive dose

- related trend was observed

for the incidence of hemangiosarcomas and mammary adenocarcinomas in female rats, hepatocellular

carcinoma in male mice, and endometrial stromal pol yps in female mice. However, only the incidence of

endometrial stromal polyps in female mice exposed to 3 ,331 mg/kg /day, 5 days/week was significantly

increased over the corresponding control animals. When only male mice surviving at least 52 weeks were

examined, there was a significant increase in the incidence of hepatocellular carcinomas in the

2,885 mg/kg /day group. There are several limitations to this study. Survival was poor in both treated and

control animals, thereby limiting the validity of th ese results. Although survival was significantly lower

in the exposed groups , it is not clear that the increase in mortality was treatment -related. Furthermore,

there were no other treatment -related effects on body weight, clinical signs, or the incidence of nonneoplastic lesions. Because of the high mortality in both the treated and control animals, the authors

concluded that not enough animals survived to be at risk for late-developing tumors. Thus, though the

results of this bioassay suggest that 1, 1- dichloroethane is carcinogenic to rats and mice, the evidence is

not conclusive.

The carcinogenicity of 1,1- dichloroethane was also examined in mice exposed to 155 or 465 mg/kg/day

of the compound in the drinking water for 52 weeks (Klaunig et al. 1986) . A two

- stage carcinogenesis

protocol was also employed in this study to assess the ability of 1,1-dichloroethane to act as a tumor

promoter. Neither 1,1-dichloroethane- treated animals initiated with diethylnitrosamine (DENA) or

animals treated with 1,1- dichloroethane without initiation showed a significant increase in the incidence

of lung or liver tumors over their corresponding controls. However, the conclusion that 1,1-dichloroethane is not a tumor promoter may not be entirely justified since a maxi mal response was observed in

terms of tumor incidence in the DENA-alone-treated mice (100% tumor incidence at 52 weeks).

Therefore, an increase in the incidence of liver tumors due to 1,1 -dichloroethane following DENA

initiation, if it existed, could not have been detected. Furthermore, since measurement of water

consumption and replenishment were only done once a week, there was no way to determine the extent, if

any, evaporation contributed to loss of the test chemical and affected the reported level of exposure.

However, precautions were taken to minimize the loss of test chemical during the 1

- week period; amber

bottles with Teflon stoppers and double sipper tubes were used. Since 1,1-dichloroethane is a volatile

***DRAFT FOR PUBLIC COMMENT***31 1,1

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3. HEALTH EFFECTS

chemical, this may present a limitatio n to the interpretation of results obtained from drinking water

administration.

The difference in results (e.g., induction of liver tumors) between the NCI (1977) and Klaunig et

al. (1986) studies may be due to the method of administration, vehicle, and/or doses used. The

pharmacokinetics of 1,1-dichloroethane may vary considerably when administered in drinking water ad

libitum over a week as compared to bolus doses given in corn oil. Evidence obtained with carbon

tetrachloride indicates that corn oil li kely acts as a reservoir in the gut to delay and diminish the systemic

absorption of the lipophilic chemical, while such a chemical is probably rapidly absorbed when ingested

in water (Kim et al. 1990a, 1990b). Furthermore, the doses given to mice by gava ge were approximately

6 times higher than the drinking water concentrations. Sufficient information is not available to assess the

contributions of these factors to the apparently disparate responses.

Milman et al. (1988) examined the carcinogenic potent ial of 1,1

- dichloroethane in initiation and

promotion assays. In partially hepatectomized Osborne- Mendel rats receiving a single gavage dose of

700 mg/kg 1,1-dichloroethane in corn oil followed by dietary exposure to phenobarbitol for 7 weeks,

there were no alterations in gamma

- glutamyltranspeptidase (GGT)

- altered foci. However, in the

promotion assay in which partially hepatecomized Osborne- Mendel rats received an intraperitoneal dose

of diethylnitrosamine followed by gavage administration of 700 mg/kg 1,1- dichloroethane in corn oil

5 days/week for 7 weeks , there was an increase in the total number of GGT- altered foci.

3.2.3 Dermal Exposure

N o studies were located regarding the following health effects in humans or animals after dermal

exposure to 1, 1- dichloroethane:

3.2.3.1 Death

3.2.3.2 Systemic Effects

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

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3.3 GENOTOXICITY

A l imited number of studies have examined the genotoxicity of 1,1-dichloroethane. No studies were

loca ted regarding in vivo genotoxic effects in humans. The genotoxic potential of 1,1- dichloroethane has

been investigated in vitro in bacteria, fungus, and m ammalian systems; the results of these studies are

summarized in Table 3-3

. 1,1- Dichloroethane did not result in an increase in reverse mutations in

Salm onella typhimurium strains with or without metabolic activation in Ames assays (Nohmi et al. 1985;

Sim mon et al. 1977). In contrast, Riccio et al. (1983 , as reported in an abstract ) and Milman et al. (1988)

reported positive mutagenic alterations in S. typhimurium exposed to 1,1-dichloroethane vapor in a

desiccator assay in the presence and absence of S9 mix. Negative findings for mutagenicity were

observed in Saccharomyes cerevisiae exposed to 1,1

- dichloroethane, with or without metabolic activation

(Bronzetti et al. 1987).

Simil arly, negative genotoxicity results have been observed in mammalian cell assays. In vitro exposure

to 1,1-dichloroethane did not induce increases in cell transformations in BALB/C- 3T3 cells (Milman et al.

1988; Tu et al. 1985) or chromosomal aberrations in Chinese hamster lung fibroblasts (Matsuoka et al.

1998). However, an inc rease in Simian adenovirus (SA7)

- induced transformations was observed in

Syrian hamster embryo cells (Hatch et al. 1983) and an increase in DNA repair was found in hepatocytes

from Osborne-Mendel rats and B6C3F1 mice (Milman et al. 1988).

In an in vivo st udy by Colacci et al. (1985), 1,1-dichloroethane (98% purity) was found covalently bound

to nucleic acids and proteins from liver, lung, kidney, and stomach of male rats and mice 22 hours

following a single intraperitoneal injection of approximately 1.2 mg/kg. In vitro binding of

1,1- dichloroethane to nucleic acids and proteins was mediated by liver P -450 dependent microsomal

mixed function oxidase system. Glutathione-S- transferase (GSH) shifted the equilibrium of the

enzymatic reaction and thereby decrea sed binding, presumably by reducing the amount of toxic

metabolite available for binding to macromolecules. On the other hand, phenobarbitone increased

binding by increasing cytochrome P-450 activity, thus generating more toxic metabolites available for

b inding to macromolecules. Presumably, the metabolites generated from P -450 enzymatic action on

1,1-dichloro ethane bind to cellular macromolecules. Lung microsomes were weakly effective whereas

kidney and stomach microsomal fractions were ineffective. Therefore, the binding to macromolecules of

various organs detected in vivo may have been due to a stable hepatic metabolite that was circulated to

reach extrahepatic organs. Pretreatment with phenobarbitone enhanced the binding to DNA, microsomal

RNA and proteins while addition of glutathione-s- transferase to the microsomal systems caused

***DRAFT FOR PUBLIC COMMENT***Results

With Without Species (test system) End point activation activation Reference

Prokaryotic organis ms: Salmonella typhimuriu,m strains TA97, TA98, TA100, and TA102 (Ames ass a y)

S. typhimurium, strains TA1535, TA1537, TA1538, TA98, and TA100 (Ames ass a y)

S. typhimurium, strai ns TA1537, TA98, TA100, and TA1535 (dessicator assay; vapor exposure)

S. typhimurium, strains TA1535, TA98, and TA100 (Ames ass ay ; dessicator )

Eukaryotic organisms:

Saccharomy ces cerevisiae D7

Mammalian cells

Syrian hamster embryo (cell transformation assay; vapor exposure)

Osborne

- Mendel rat and B6C3F1 mouse hepatocytes

BALB/C

- 3T3 (cell transformation assay; exposure in sealed chamber)

BALB/C

- 3T3 (cell transformation assay; exposure in sealed chamber)

Chinese hamster lung fibroblasts (chromosomal aberration assay; exposure in sealed chamber) Gene mutation

Gene mutation

Gene mutation

Gene mutation

Gene mutation

DNA viral

transformation

DNA repa ir

Cell transformation

Cell transformation

Chromosomal

aberrations – – Nohmi et al. 1986

– – Simmon et al. 1977

+ + Riccio et al. 1983

+ + Milman et al. 1988

– – Bronzetti et al. 1987

No data + Hatch et al. 1983

No data + Milman et al. 1988

No data
– Tu et al. 1985

No data
– Milman et al. 1998

– – Matsuoka et al. 1998) 

### Table 3

- 3. Genotoxicity of 1,1

- Dichloroethane **In Vitro**

C = negative result; + = positive result; ± = weakly positive 33 1,1

- DICHLOROETHANE

3. HEALTH EFFECTS

***DRAFT FOR PUBLIC COMMENT***34 1,1

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suppression of binding. Because only rad ioactivity was measured it is difficult to determine whether the

μmole bound represents 1,1-dichloroethane or its metabolite(s). However, the fact that binding is

enhanced with induction of P

- 450 suggests that it represents the metabolite(s). Thus, GSH a ppears to

play a detoxification role in the metabolism of 1,1 -dichloroethane. The fact that 1,1-dichloroethane binds

to nucleic acid suggests that it may have a potential to produce mutation in a mammalian system.

3.4 TOXICOKINETICS

3.4.1 Absorption

3.4.1.1 Inhalation Exposure

N o studies were located in humans or animals regarding the absorption of inhaled 1,1-dichloroethane.

However, its use as a gaseous anesthetic agent in humans provides evidence of its absorption.

Furthermore, the volatile and lipophilic nature of 1,1-dichloroethane favors pulmonary absorption.

Structurally related chlorinated aliphatics and gaseous anesthetics are known to be rapidly and extensively

absorbed from the lung. The total amount absorbed from the lungs will be directly proportional to the

concentration in inspired air, the duration of exposure, the blood/air partition coefficient of

1,1-dichloroethane, its solubility in tissues, and the individual's ventilation rate and cardiac output. One

of the most important factors controlling pulmonary absorption is the blood/air partition coefficient of the

chemical. The concentration of the chemical and the duration of exposure are also important

determinants of the extent of systemic absorption.

It is known that an isomer of 1,1-dichloroethane, 1,2- dichloroethane, is well

- absorbed following

inhalation exposure. However, the blood/air partition coefficient for 1,2- dichloroethane is approximately

4 times that of 1,1

- dichloroethane. This suggests that 1,1 -dichloroethane would not be absorbed into the

blood from air as readily as 1,2-dichloroethane, but it will still be well absorbed from the lung (Sato and

Nakajima 1987).

3.4.1.2 Oral Exposure

N o studies were located that quantitated the absorption of ingested 1,1-dichloroethane in humans or

animals. However, when 700 mg [ 14 C] -1,1-dichloroethane/kg was orally administered to rats and mice,

absorption was evidenced by the presence of radiolabel in expired air and the presence of radiolabeled

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metabolites in urine, although there was no quantitative assessment made of the extent or rate of

absorption (Mitoma et al. 1985).

3.4.1.3 Dermal Exposure

N o studies were located regarding the absorption of 1,1-dichloroethane in humans or animals following

dermal exposure. However, Reid and Muianga (2012) reported evidence that 1,1- dichloroethane

penetrates the skin. 1,1-Dichloroethane was applied to the shaved abdominal skin of rabbits that were

fitted with masks to prevent inhalation of the compound. Exhaled air from the rabbits was passed into

pure alcohol, and the presence of halogen was tested by flaming a copper wire introduced into it. The

green color observed after 1 hour indicated that the halogen ion was absorbed into the bloodstream,

although no quantitative assessment of the extent or rate of absorption was possible.

3.4.2 Distribution

3.4.2.1 Inhalation Exposure

N o studies were located in humans or animals regarding the distribution of 1,1- dichloroethane following

inhalation exposure. However, sin ce this chemical was once used as a gaseous anesthetic, it can be

assumed that it is distributed to the central nervous system as well as to the other tissues of the body.

Tissue uptake of halocarbons such as 1,1 -dichloroethane is governed by the affinity of each tissue for the

lipophilic chemical (i.e., the higher the lipid content of a tissue, the greater its uptake of 1,1-dichloroethane) (Sato and Nakajima 1987).

3.4.2.2 Oral Exposure

N o studies were located regarding the distribution of 1,1-dichloroethane following oral exposure in

humans or animals.

3.4.2.3 Dermal Exposure

N o studies were located regarding the distribution of 1,1-dichloroethane following dermal exposure in

humans or animals.

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3.4.2.4 Other Routes of Exposure

R ats and mice were intraperitoneally injected with 1.2 mg [ 14 C] -1,1- dichloroethane/kg and sacrificed

22 hours later. 1,1-Dichloroethane was covalently bound to proteins, RNA, and DNA of liver, kidney,

lung, and stomach. The extent of binding was greatest in the tiss ue proteins and least in the DNA.

Binding to rat and mouse DNA was greatest in the stomach and liver, respectively (Colacci et al. 1985).

Although distribution of 1,1-dichloroethane very likely occurs to other tissues, the liver, kidney, lung, and

stomach were the only tissues analyzed in this study.

3.4.3 Metabolism

T he metabolism of 1,1- dichloroethane has not been extensively characterized. In vivo studies of the

metabolism of 1,1- dichloroethane in humans and animals are very limited. Elucidatio n of 1,1 -dichloroethane's metabolic scheme to date is primarily based on in vitro studies. In general, the identification of

specific metabolites and the monitoring of enzyme activities indicate that the biotransformation of

1,1- dichloroethane is mediate d by hepatic microsomal cytochrome P-450 system.

In rats and mice orally administered 700 or 1,800 mg/kg, respectively, 1,1-dichloroethane (5 days/week

for 4 weeks followed by a single dose of radiolabelled 1,1- dichloroethane), most of the radiolabel wa s

detected in expired air; the investigators assumed that this was parent compound (Mitoma et al. 1985).

Forty -eight hours after oral administration, 7.4 and 29.3% of the radiolabel was detected in the urine,

carcass, or expired carbon dioxide. The inves tigators assumed that this represented metabolized

1,1- dichloroethane; however, only radiolabel was measured in the carcass. It is likely that the ingested

radiolabeled 1,1- dichloroethane underwent first

- pass extraction by the liver. It is possible that high doses

used in this study exceeded the capacity of the animals to metabolize 1,1 -dichloroethane . The

radiolabeled compound that was not excreted unchanged in the expired air was probably largely

metabolized in the liver, followed by subsequent redistribution of labeled metabolites to other organs

prior to their excretion.

An in vitro study demonstrated cytochrome P450 metabolism of 1,1-dichloroethane. McCall et al. (1983)

demonstrated 1,1-dichloroethane binding to hepatic microsomal cytochrome P450 f rom rats; as compared

to microsomes from untreated rats, cytochrome P450 binding was 2.25 times higher, per mole of

cytochrome, in microsomes from phenobarbital- stimulated rats. Administration of β-naphthaflavone had

no effect on the extent of 1,1 -dichloroethane binding to cytochrome P450 binding. In vitro exposure of

hepatic microsomal to 1,1-dichloroethane also stimulated NADPH oxidation. The rate and extent of

***DRAFT FOR PUBLIC COMMENT***37 1,1

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1,1- dichloroethane metabolism was increased 6.3 times in the hepatic microsomes of rats that were

induced by chronic ethanol consumption (Sato et al. 1980). .

Metabolism of 1,1- dichl oroethane by hepatic microsomes resulted in the production of acetic acid as the

major metabolite and 2,2-dichloroethanol, mono- , and dichloroacetic acid as minor metabolites

( Table 3- 4 ) (McCall et al. 1983). On the basis of these results, pathways for the metabolism of

1,1-di chloroethane were proposed ( Fig ure 3-3 ). The initial steps in the metabolism of 1,1-dichloroethane

we re proposed to involve cytochrome P-450-dependent hydroxylations at either carbon. Hydroxylation at

C-1 would result in the production of an unstable alpha- haloalcohol, which can lose HCl to yield acetyl

chloride. An alternative, but less favorable reaction, would be a chlorine shift to yie ld chloroacetyl

chloride. These acyl chlorides can react with water to generate free acids or react with cellular

constituents. Hydroxylation at C-2 would produce 2,2-dichloroethanol, which would undergo subsequent

oxidation to dichloroacetaldehyde and dichloroacetic acid (McCall et al. 1983).

Chlor oe thanes have been shown to undergo dechlorination by an enzyme system that is similar to the

hepatic microsomal mixed function oxidase system (Van Dyke and Wineman 1971). Dechlorination was

inducible by phenobarbital and required oxygen and NADPH. However, dechlorination also required a

factor from the cytosolic fraction of the liver homogenate for optimal dechlorinating activity. In terms of

structural requirements, dechlorination was enhanced if the car bon atom containing the chlorine had only

one hydrogen. In a microsomal incubation, 13.5% of the 36 Cl of 1,1 -dichloroethane was enzymatically

removed after 30 minutes, while <0.5% of the 36 Cl of 1,2 -dichloroethane was removed (Van Dyke and

Wineman 1971).

Under hypoxic conditions, 1,1- dichloroethane gives rise to free radicals. However, its ability to develop

free radicals is much less when compared to other chlorinated hydrocarbons like trichloroethane and

carbon tetrachloride. It has been suggested th at these free radicals possess the potential to induce toxic

and carcinogenic effects. There is no correlation between the ease of free radical activation, covalent

binding formation, or carcinogenic potency (Tomasi et al. 1984).

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### Table 3 -4 . Production of Metabolites from 1,1

- Dichloroethane with Hepatic

Microsomes from Phenobarbital

- Induced Rats

Metabolic production a

Metabolites (nmoles/mg microsomal protein/20 minutes)

Acetic acid 179 (15)

2,2

- Dichloroethane 0.12 (0.02)

Chloroacetic acid 0.22 (0. 08)

Dichloroacetic acid 0.048 (0.005)

Chloroacetaldehyde <0.07 (0.03)

a Values represent means (standard deviation) for determinations in triplicate on three to five separate preparations of hepatic microsomes.

Source: McCall et al. 1983 38 1,1

- DICHLOROETHANE

3. HEALTH EFFECTS

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- DICHLOROETHANE

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### Figure 3 -3 . Proposed Metabolic Scheme for 1,1

- Dichloroethane

Cl 2 HCCH 3 Cl 2 HCCH 2 OH

P450 (C-1) 2,2-dichloroethanol C

O Cl 2 HC H

dichloroacetaldehyde C

O OH Cl 2 HC

dichloroacetic acid

[HOCl 2 CCH 3 ]

alpha-haloalcohol chlorine
shift

C

O [ClCH 2 Cl]

chloroacetyl

chloride -HCl H 2 O C O

ClCH 2 OH

monochloroacetic

acid

-HCl C

O [Cl CH 3 ]

acetyl

chloride -HCl H 2 O CH 3 COOH

acetic

acid

Source: McCall et al. 1983 P450 (C-2)

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3.4.4 Elimination and Excretion

3.4.4.1 Inhalation Exposure

No empirical data on the elimination of excretion of 1,1- dichloroethane in humans or animals were

identified. Sato and Nakajima (1987) predicted that 59% of inhaled 1,1-dichloroethane would be

metabolized and excreted in the urine and 41% w ould be eliminated in expired air.

3.4.4.2 O ral Exposure

Mi toma et al. (1985) examin ed excretion of 1,1-dichloroethane in rats and mice administered

1,1-dichloroethane via gavage 700 or 1,800 mg/kg, respectively, 5 days/week for 4 weeks followed by a

single dose of radiolabelled 1,1-dichloroethane. In the rats, 86% of the administered do se was excreted in

expired air 5% expired as carbon dioxide and 0.9% was detected in the urine

. In mice , 70% was excreted

in expired air , 2 5% was expired as car bon dioxide, and 1.6% was detected in urine

. Because rats and

mice were administered different doses, a determination cannot be made as to whether the differences in

excretion and metabolism a re due to species differences or are a reflection of different doses.

.

3.4.4. 3 Dermal Exposure

No studies were located in humans or animals regarding ex cretion of 1,1-dichloroethane following dermal

exposure

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

Ph ysiologically based pharmacokinetic (PBPK) models use mathematical descriptions of the uptake and

disposition of c hemical 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, pri marily 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

phar macodynamic (PBPD) models use mathematical descriptions of the dose

- response function to

quantitatively describe the relationship between target tissue dose and toxic end points.

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PBPK/PD models refine our understanding of complex quantitative dose behav iors by helping to

delineate and characterize the relationships between: (1) the external/exposure concentration and target

tissue dose of the toxic moiety, and (2) the target tissue dose and observed responses (Andersen and

Krishnan 1994; Andersen et al. 1987). These models are biologically and mechanistically based and can

be used to extrapolate the pharmacokinetic behavior of chemical substances from high to low dose, from

route to route, between species, and between subpopulations within a species. The biological basis of

PBPK models results in more meaningful extrapolations than those generated with the more conventional

use of uncertainty factors.

The PBPK model for a chemical substance is developed in four interconnected steps: (1) model

repres entation, (2) model parameterization, (3) model simulation, and (4) model validation (Krishnan and

Andersen 1994). In the early 1990s, validated PBPK models were developed for a number of

toxicologically important chemical substances, both volatile and no nvolatile (Krishnan and Andersen

1994; Leung 1993). PBPK models for a particular substance require estimates of the chemical substance

specific physicochemical parameters, and species

- specific physiological and biological parameters. The

numerical estimates of these model parameters are incorporated within a set of differential and algebraic

equations that describe the pharmacokinetic processes. Solving these differential and algebraic equations

provides the predictions of tissue dose. Computers then provide process simulations based on these

solutions.

The structure and mathematical expressions used in PBPK models significantly simplify the true

complexities of biological systems. If the uptake and disposition of the chemical substance(s) are

adequa tely 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

maxi mal (i.e., the safe) levels for human exposure to chemical substances (A ndersen 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 resu lts of studies where doses were higher or were administered in different species.

Figur e 3-4 shows a conceptualized representation of a PBPK model.

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### Figure 3

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

Hyp othetical Chemical Substance

Inhaled chemic

Lungs

Liver

Fat

Slowly perfused

tissues

Richly perfused

tissues

Kidney

Skin V

E

N

O

U

S

B

L

O

O

D A

R

T

E

R

I

A

L

B

L

O

O

D V
max

K
m Ingestion

GI

Tract

Feces

Urine

Chemicals contacting skin

Note: This is a conceptual representation of a physiologically based pharmacokinetic (PBPK) model for a hypothetical chemical substance. The chemical substance is shown to be absorbed via the skin, by inhalation, or by ing estion, metabolized in the liver, and excreted in the urine or by exhalation.

Source: adapted from Krishnan and Andersen 1994

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If PBPK models for 1,1 -dichloroethane exist, the overall results and individual models are discussed in

this section in ter ms of their use in risk assessment, tissue dosimetry, and dose, route, and species

extrapolations.

No PBPK models were identified for 1,1- dichloroethane.

3.5 M ECHANISMS OF ACTION

3.5.1 Pharmacokinetic Mechanisms

No i nformation was identified on t he pharmacokinetic mechanisms of action of 1,1 -dichloroethane.

3.5.2 Mechanisms of Toxicity

Th ere are limited data to identify the critical targets of 1,1

- dichloroethane toxicity or to elucidate the

mode of action for the observed effects.

3.5.3 An imal

- to

- Human Extrapolations

The inhalation study by Hofmann et al. (1971) found species differences in the renal toxicity of

1,1-dichloroethane. Crystaline precipitations and tubular obstruction were observed in cats, but not in

rats, rabbits, or guin ea pigs. There are insufficient data to determine whether this would also be a relevant

end point in humans and whether humans would be as sensitive to this effect as cats.

3.6 T OXICITIES MEDIATED THROUGH THE NEUROENDOCRINE AXIS

Recen tly, attention h as focused on the potential hazardous effects of certain chemicals on the endocrine

system because of the ability of these chemicals to mimic or block endogenous hormones. Chemicals

with this type of activity are most commonly referred to as endocrine dis ruptors . However, appropriate

terminology to describe such effects remains controversial. The terminology endocrine disruptors

, initially used by Thomas and Colborn (1992), was also used in 1996 when Congress mandated the EPA to

develop a screening program for “...certain substances [which] may have an effect produced by a

naturally occurring estrogen, or other such endocrine effect[s]...”. To meet this mandate, EPA convened a

panel called the Endocrine Disruptors Screening and Testing Advisory Committee (EDSTAC), and in

1998, the EDSTAC completed its deliberations and made recommendations to EPA concerning endocrine

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disruptors . In 1999, the National Academy of Sciences released a report that referred to these same types

of chemicals as hormonally active agents . The terminology endocrine modulators has also been used to

convey the fact that effects caused by such chemicals may not necessarily be adverse. Many scientists

agree that chemicals with the ability to disrupt or modulate the endocrine system ar e a potential threat to

the health of humans, aquatic animals, and wildlife. However, others think that endocrine- active

chemicals do not pose a significant health risk, particularly in view of the fact that hormone mimics exist

in the natural environment. Examples of natural hormone mimics are the isoflavinoid phytoestrogens

(Adlercreutz 1995; Livingston 1978; Mayr et al. 1992). These chemicals are derived from plants and are

similar in structure and action to endogenous estrogen. Although the public h ealth significance and

descriptive terminology of substances capable of affecting the endocrine system remains controversial,

scientists agree that these chemicals may affect the synthesis, secretion, transport, binding, action, or

elimination of natural h ormones in the body responsible for maintaining homeostasis, reproduction,

development, and/or behavior (EPA 1997). Stated differently, such compounds may cause toxicities that

are mediated through the neuroendocrine axis. As a result, these chemicals may play a role in altering,

for example, metabolic, sexual, immune, and neurobehavioral function. Such chemicals are also thought

to be involved in inducing breast, testicular, and prostate cancers, as well as endometriosis (Berger 1994;

Giwercman et al. 1 993; Hoel et al. 1992).

No studies were located regarding endocrine disruption in [humans and/or animals] after exposure to

1,1-dichloroethane.

No in vitro studies were located regarding endocrine disruption of 1,1 -dichloroethane.

3.7 CHI LDREN’S SUSCE PTIBILITY

Th is section discusses potential health effects from exposures during the period from conception to

maturity at 18 years of age in humans, when all biological systems will have fully developed. Potential

effects on offspring resulting from exposures of parental germ cells are considered, as well as any indirect

effects on the fetus and neonate resulting from maternal exposure during gestation and lactation.

Relevant animal and in vitro models are also discussed.

Children are not small adults. They differ from adults in their exposures and may differ in their

susceptibility to hazardous chemicals. Children’s unique physiology and behavior can influence the

extent of their exposure. Exposures of children are discussed in Section 6.6, Exposures of Children.

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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 childre n 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 fetus/infant has an immature (developing) blood-brain

barrier that past literature has often described as being leaky and poorly intact (Costa et al. 2004).

However, current evidence suggests that the blood

- brain barrier is anatomically and physically intact at

this stage of development, and the restrictive intracellular junctions that exist at the blood

- CNS interface

are fully formed, intact, and functionally effective (Saunders et al. 2008, 2012).

However, during development of the blood- brain barrier, there are differences between fetuses/infants and

adults which are toxicologically important. These differences mainly involve variatio ns in physiological

transport systems that form during development (Ek et al. 2012). These transport mechanisms (influx and

efflux) play an important role in the movement of amino acids and other vital substances across the

blood- brain barrier in the deve loping brain; these transport mechanisms are far more active in the

developing brain than in the adult. Because many drugs or potential toxins may be transported into the

brain using these same transport mechanisms —the developing brain may be rendered mor e vulnerable

than the adult. Thus, concern regarding possible involvement of the blood-brain barrier with enhanced

susceptibility of the developing brain to toxins is valid. It is important to note however, that this potential

selective vulnerability of the developing brain is associated with essential normal physiological

mechanisms; and not because of an absence or deficiency of anatomical/physical barrier mechanisms.

The presence of these unique transport systems in the developing brain of the fetus/i nfant is intriguing; as

it raises a very important toxicological question as to whether these mechanisms provide protection for

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3. HEALTH EFFECTS

the developing brain or do they render it more vulnerable to toxic injury. Each case of chemical exposure

should be assessed on a case

- by

- case basis. Research continues into the function and structure of the

blood-brain barrier in early life (Kearns et al. 2003; Saunders et al. 2012; Scheuplein et al. 2002).

Many xenobiotic metabolizing enzymes have distinctive developmental pat terns. 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 als o be differences in excretion,

particularly in newborns who 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 d iffer in their capacity to repair damage from chemical insults. Children also

have a longer remaining lifetime in which to express damage from chemicals; this potential is particularly

relevant to cancer.

Certain characteristics of the developing human may increase exposure or susceptibility, whereas others

may decrease susceptibility to the same chemical. For example, although infants breathe more air per

kilogram of body weight than adults breathe, this difference might be somewhat counterbalanced by t heir

alveoli being less developed, which results in a disproportionately smaller surface area for alveolar

absorption (NRC 1993).

Information on children’s susceptibility to the toxic effects of 1,1 -dichloroethane is limited to a

developmental toxicity st udy in rats (Schwetz et al. 1974) that found an increase in the incidence of

delayed ossifications in the fetuses of dams exposed to 6 ,000 ppm 1,1-dichloroethane on gestation

days 6–15. An in vitro study (Andrews et al. 2002; only available as an abstract ) utilizing rat whole

embryo cultures reported eye defects in at 17.9 mM; this concentration also reported in 35%

embryolethality.

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).

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The National Report on Human Exposure to Environmental Chemicals provides an ongoing assessment

of the exposure of the U.S. population to environmental chemicals using biomonitoring. This report is

available at http://www.cdc.gov/exposurereport/. The biomonitoring data for 1,1

- dichloroethane from

this report is discussed in Section 6.5. A biomarker of exposure is a xenobiotic s ubstance 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 su bstance itself, substance

- specific metabolites in readily

obtainable body fluid(s), or excreta. However, several factors can confound the use and interpretation of

biomarkers of exposure. The body burden of a substance may be the result of exposures from more than

one source. The substance being measured may be a metabolite of another xenobiotic substance (e.g.,

high urinary levels of phenol can result from exposure to several different aromatic compounds).

Depending on the properties of the substance (e.g., biologic half-life) and environmental conditions (e.g.,

duration and route of exposure), the substance and all of its metabolites may have left the body by the

time samples can be taken. It may be difficult to identify individuals exposed to hazardo us substances

that are commonly found in body tissues and fluids (e.g., essential mineral nutrients such as copper, zinc,

and selenium). Biomarkers of exposure to 1,1- 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 1,1-dichloroethane are discussed in Section 3.8.2.

A biomarker of susceptibility is an indicator of an inherent or acquired limitation of an organism's ability

to respond to the challenge of exposure to a specific xenobiotic substance. It can be an intrinsic genetic or

other characteristic or a preexisting disease that results in an increase in absorbed dose, a decrease in the

biologically effective dose, or a target tissue response. If biomarkers of susceptibility exist, they are

discussed in Section 3.10, Populations That Are Unusually Susceptible.

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3.8.1 Biomarkers Used to Identify or Q uantify Exposure to 1,1

- Dichloroethane

As summarized in Section 6.5, 1,1-dichloroethane was not detected in blood samples collected from the

National Health and Nutrition Examination Survey (2003–2004). No other biomarkers that could be used

to iden tify or quantify exposure to 1,1- dichloroethane were identified.

3.8.2 Biomarkers Used to Characterize Effects Caused by 1,1

- Dichloroethane

1,1- Di chloroethane was used as an anesthetic in the early part of the 20 th century (Konietzko 1984 ; Reid

and M uianga 2012 ). No information was available on blood levels associated with anesthesia or the

occurrence of anesthesia

- induced cardiac arrhythmias.

3.9 I NTERACTIONS WITH OTHER CHEMICALS

No i nformation was located regarding toxic interactions of 1,1-dichloroethane with other xenobiotics.

Evidence exists to indicate that 1,1

- dichloroethane is detoxified by glutathione (Colacci et al. 1985).

Thus, it is likely that other substances that deplete glutathione stores such as other chlorinated

hydrocarbons ( e.g., 1,1- dichloroethene and 1,2 -dichloroethane), acetaminophen, and bromobenzene may

enhance the toxicity of 1,1- dichloroethane. Substances that alter the activity of the microsomal enzymes

that are responsible for the metabolism of 1,1 -dichloroethane ma y also affect the toxicity of this chemical.

For example, it has been shown that ethanol increases the metabolism of 1,1-dichloroethane in vitro (Sato

et al. 1980).

3.10 PO PULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE

A s usceptible population will exhibit a different or enhanced response to 1,1-dichloroethane than will

most persons exposed to the same level of 1,1-dichloroethane in the environment. Reasons may include

genetic makeup, age, health and nutritional status, and exposure to other toxic substan ces (e.g., cigarette

smoke). These parameters result in reduced detoxification or excretion of 1,1-dichloroethane, or

compromised function of organs affected by 1,1-dichloroethane. Populations who are at greater risk due

to their unusually high exposure to 1,1 -dichloroethane are discussed in Section 6.7, Populations with

Potentially High Exposures.

No populations unusually susceptible to 1,1- dichloroethane or chlorinated ethanes in general have been

identified. NIOSH (1978) has identified the following individuals as possibly being at increased risk

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3. HEALTH EFFECTS

from exposure to 1,1- dichloroethane: (1) individuals with skin disease because of the purported dermal

irritant effects induced by 1,1 -dichloroethane; ( 2) individuals with liver disease because of the role o f this

organ in the biotransformation and detoxification of xenobiotics such as 1,1-dichloroethane;

(3) Individuals with impaired renal function because of the limited evidence that 1,1- dichloroethane is

nephrotoxic in animals; and (4) individuals with chr onic respiratory disease because of the purported

respiratory irritant effects induced by 1,1 -dichloroethane. Although there are no data to substantiate this,

additional populations that may be unusually susceptible to 1,1- dichloroethane include children and the

elderly because of immature or compromised metabolic capabilities, and phenobarbital or alcohol

consumers because of the ability of these substances to alter the activity of the cytochrome P -450 system.

It should be noted that no reliable data we re found regarding dermal or respiratory irritant effects of

1,1-dichloroethane.

3.11 M ETHODS FOR REDUCING TOXIC EFFECTS

Th is section will describe clinical practice and research concerning methods for reducing toxic effects of

exposure to 1,1-dichlor oethane . However, because some of the treatments discussed may be experimental

and unproven, this section should not be used as a guide for treatment of exposures to 1,1 -dichloroethane

. When specific exposures have occurred, poison control centers and medical toxicologists should be

consulted for medical advice. No texts providing specific information about treatment following

exposures to 1,1 -dichloroethane were identified.

3.11.1 Reducing Peak Absorption Following Exposure

No i nformation specific to 1,1 -dichloroethane was identified.

3.11.2 Reducing Body Burden

No i nformation specific to 1,1 -dichloroethane was identified.

3.11.3 Interfering with the Mechanism of Action for Toxic Effects

Th e mechanism s of toxicity have not been identified for 1,1-dichloroethane.

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3.12 ADEQUACY OF THE DATABASE

Section 104(I)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with the

Administrator of EPA and agencies and programs of the Public Health Service) to assess whether

adequate information on the health effects of 1,1-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 de signed to determine the health effects (and

techniques for developing methods to determine such health effects) of 1,1-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 1,1

- Dichloroethane

Th e existing data on health effects of inhalation, oral , and derm al exposure of humans and animals to

1,1-dichloroethane are summarized in Figur e 3-5

. The purpose of this figure is to illustrate the existing

infor mation concerning the health effects of 1,1-dichloroethane. Each dot in the figure indicates tha t one

or more studies provide information associated with that particular effect. The dot does not necessarily

imply anything about the quality of the study or studies, nor should missing information in this figure be

interpreted as a “data need”. A data need, as defined in ATSDR’s Decision Guide for Identifying

Substance-Specific Data Needs Related to Toxicological Profiles (Agency for Toxic Substances and

Disease Registry 1989), is substance

- specific information necessary to conduct comprehensive public

health assessments. Generally, ATSDR defines a data gap more broadly as any substance

- specific

information missing from the scientific literature.

Figure 3 -5 graphically depicts the information that currently exists on the health effects of

1,1-dichl oro ethane. The literature reviewed concerning the health effects of 1,1

- dichloroethane in

humans consisted solely of an anecdotal report describing the occurrence of cardiac arrhythmias when

this compound was used as a gaseous anesthetic. Chlorinated alipha tics as a class are known to cause

central nervous system depression, and respiratory tract and dermal irritation when humans are exposed

by inhalation to sufficiently high levels. It has been inferred that 1,1- dichloroethane causes these effects,

but no reliable data were found that verified this activity.

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3 . H E A L TH E FFE C TS



### Figure 3

- 5. Existing Information on Health Effects of 1,1

- Dichloroethane

Inhalation

Oral

Dermal Death Acute Intermediate Chronic Immunologic/Lymphoretic Neurologic Reproductive Developmental Genotoxic Cancer Systemic

Human

Animal

Existing Studies Inhalation

Oral

Dermal Death Acute Intermediate Chronic Immunologic/Lymphoretic Neurologic Reproductive Developmental Genotoxic Cancer Systemic

* * * DRA F T F O R P UB L I C CO M M E NT * * *52 1,1

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3. HEALTH EFFECTS

The database for the health effects of 1,1-dichloroethane in experimental animals is lacking, and the

studies reviewed co nsisted primarily of one subchronic inhalation study, one inhalation developmental

toxicity study, and two oral chronic bioassays. No information is available on the effects of

1,1-dichloroethane following dermal exposure. The limited information availab le in animals suggests that

1,1-dichloroethane may be nephrotoxic, fetotoxic, and possibly carcinogenic. The data also indicate that

1,1-dichloroethane is considerably less toxic than 1,2- dichloroethane and the tetrachlorinated aliphatics.

3.12.2 Ident ification of Data Needs

Ac ute

- Duration Exposure. No reliable information is available on the effects of acute exposure to

1,1-dichloroethane in humans. Information on the lethality of 1,1-dichloroethane following inhalation or

oral exposure of animal s comes from secondary sources ( Archer 1978; Smyth 1956). One study

examined the nonlethal toxicity of 1,1-dichloroethane following inhalation exposure (Schwetz et al.

1974); this study reported decreases in maternal weight gain and delayed ossification i n the fetuses.

Because the potential systemic toxicity of 1,1

- dichloroethane has not been evaluated following acute

inhalation exposure, the database was not considered adequate for derivation of an acute-duration

inhalation MRL. The lack of oral data precluded derivation of an oral MRL for 1,1-dichloroethane.

Since the chlorinated aliphatics in general are known to cause central nervous system depression and

irritation of respiratory and ocular mucosal epithelium following single high- level exposures, more

information on the effects of acute -duration exposures to 1,1- dichloroethane by all routes would be useful

to assess more fully the acute hazards of this chemical.

Intermediate

- Duration Exposure. No reliable information is available on the effe cts of repeated

exposure in humans. Limited information is available on the effects of repeated inhalation and oral

exposures to 1,1

- dichloroethane in animals. The studies reviewed indicate that 1,1

- dichloroethane is

possibly nephrotoxic, but this effect has only been demonstrated at high doses in cats, but not in rats,

guinea pigs, or rabbits (Hofmann et al. 1971). No other toxic effects have been attributed to

1,1- dichloroethane following intermediate

- duration inhalation exposures in animals. The lack of

supporting toxicity or mechanistic data precluded using this study as the basis on an intermediate -duration

inhalation MRL

. More information on the systemic effects of repeated

- dose exposures in animals,

particularly by the inhalation route since this is the most likely route of human exposure, would be useful

to determine whether nephrotoxic effects observed in one study are an actual result of exposure to

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- DICHLOROETHANE

3. HEALTH EFFECTS

1,1-dichloroethane, to determine if 1,1- dichloroethane reacts like other chlorinated aliphatics (e.g., causes

neurotoxicity and liver toxicity), and to more fully assess potential human health hazards from repeated

exposure to 1,1 -dichloroethane. Two studies have examined the intermediate-duration oral toxicity of

1,1-dichloroethane. In a limited reported study, NCI (1977) found alterations in body weight gain in rats,

but not mice, administered 1,1

- dichloroethane for 6 weeks. In the second study, no adverse effects were

observed in mice exposed to 1,1-dichloroethane in drinking water for 52 weeks (Klaunig et al. 1986).

Additional oral studies are needed to identify sensitive targets of toxicity and establish dose -response

relationships. D ermal studies are also necessary to evaluate the toxicity of this compound.

Chronic

- Duration Exposure and Can cer. No information is available on the effects of chronic

exposure to 1,1 -dichloroethane in humans. No chronic -duration inhalation or dermal exposure studies

were identified. In chronic- duration oral exposure studies in rats and mice ( NCI1977), no nonneoplastic

alterations were observed. Without information on the targets of toxicity and dose-response relationships,

inhalation and oral MRLs cannot be derived. Additional chronic toxicity studies particularly by the

inhalation route would be useful to fully assess potential human health hazard from long-term exposure to

1,1-dichloroethane.

Two bioassays were reviewed that investigated the potential carcinogenic effect of 1,1 -dichloroethane by

the oral route of exposure in animals. One study provide d suggestive evidence of carcinogenicity, but

because there was poor survival in this study and the statistical significance of the cancer incidence is

uncertain, the results could not be considered conclusive (NCI 1977) . The other bioassay yielded

negati ve results for 1,1 -dichloroethane (Klaunig et al. 1986) . Given the limitations (high mortality)

present in the NCI (1977) study and the observations that 1,1- dichloroethane possibly forms DNA

adducts and metabolizes to free radicals, more information obta ined from well -conducted carcinogenicity

studies would be useful to assess more fully the carcinogenic potential of 1,1

- dichloroethane in humans

and animals. Studies conducted by the inhalation route would be useful.

Genotoxicity. The genotoxic pote ntial of 1,1

- dichloroethane has been investigated in in vitro assays ;

in vivo genotoxicity studies are necessary to evaluate the genotoxic potential of this chemical. In general,

these studies provide suggestive evidence that 1,1- dichloroethane is not gen otoxic. 1,1-Dichloroethane

has been observed to enhance cell transformation in Syrian hamster embryo cells (Hatch et al. 1983) and

results suggest that 1,1

- dichloroethane or a metabolite can bind to cellular macromolecules such as DNA

(Colacci et al. 1985 ). More information on the genotoxic effects of 1,1-dichloroethane in animals both in

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3. HEALTH EFFECTS

vitro and in vivo would be useful to resolve the discrepancies in the present data and to assess the

genotoxic hazard of this chemical in humans.

Reproductive Toxicity. No information on the reproductive effects of 1,1- dichloroethane in humans

or animals is available. Reproductive toxicity studies in animals would be useful particularly by the

inhalation route since this is the most likely route of human exposure.

Developmental Toxicity. No information on the developmental effects of 1,1- dichloroethane in

humans is available. One study was located that investigated the developmental effects of inhaled

1,1- dichloroethane in animals (Schwetz et al. 1974) . The re sults from this study indicated that

1,1- dichloroethane is fetotoxic in rats, causing retarded fetal development (i.e., delayed ossification of the

vertebrae) in the presence of decreases in maternal food consumption and body weight gain.

Additionally, we ll -conducted developmental toxicity studies on 1,1-dichloroethane, particularly by the

inhalation route since this is the most likely route of human exposure, would be useful to verify the data

from the single study that suggest this compound may cause adv erse developmental effects.

Immunotoxicity. No information is available on the immunotoxic effects of 1,1- dichloroethane in

humans or animals. Immunotoxicity studies in animals, particularly by the inhalation route since this is

the most likely rout e of human exposure, would be useful to assess the potential risk for

1,1-dichloroethane-induced adverse immunologic effects in humans.

Neurotoxicity. Chlorinated aliphatics as a class are known to cause central nervous system depression

in humans exposed by inhalation to sufficiently high levels. 1,1- Dichloroethane can also cause this effect,

evidenced by its former use as an anesthetic. However, no reliable data were found that indicated a

threshold level for this effect. No data (behavioral, histopathological, neurochemical, or

neurophysiological) are available on possible neurotoxic effects of long- term low level exposures to

1,1-dichloroethane. More information on potential short- and long-term neurotoxic effects of inhaled

1,1-dichloroethane would be useful to determine whether this compound can produce neurotoxic effects

following low-level, long-term exposures, and to determine the threshold exposure level for

1,1-dichloroethane- induced central nervous system depression.

Epidemiological and Human Dosimetry Studies. No epidemiological studies were located on

1,1- dichloroethane. Well -controlled epidemiological studies of people living in close proximity to areas

where 1,1-dichloroethane contamination of surface water and groundwater or air is known to have

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3. HEALTH EFFECTS

occurred, people living near hazardous waste sites, and of occupationally exposed people could add to the

limited database and clarify health effects in humans induced by 1,1-dichloroethane. However, while this

information would be useful, it is unlikely that it could be easily obtained from occupational studies.

Other short

- chain halogenated hydrocarbons are usually encountered in the same facilities where

1,1-dichloroethane is manufactured or used, thus confounding the results obtained in such a study.

Biomarkers of Exposure and Effect. For high exposure to 1,1- dichloroethane, the levels of this

compound in the blood, urine, and breath may be used for biomarkers of exposure. However, these

methods should be more sensitive and quan titative. The formation of DNA adducts has been suggested,

and if they do occur in vivo , they may serve to identify long-term exposure to 1,1- dichloroethane. The

development of methods for detecting metabolites in the fluids and tissue of humans is neede d to indicate

1,1- dichloroethane exposure.

Biomarkers of effect would be useful for identifying 1,1-dichloroethane- specific injury (e.g.,

hepatotoxicity, renal toxicity, neurotoxicity) for short-, intermediate-, and long-term exposure. Presently,

no biom arkers of effect are available; however, DNA adducts may be useful for indicating

carcinogenicity in animals or humans following chronic exposure to 1,1-dichloroethane.

Absorption, Distribution, Metabolism, and Excretion. Studies of the toxi cokinetics of

1,1-dichloroethane are very limited. Much of the information regarding the disposition of 1,1-dichloroethane is based on indirect evidence. Toxi cokinetic data are useful for providing information on

mechanisms of toxicity and can often support findin gs of toxicity studies.

Absorption of 1,1- dichloroethane occurs following exposure via all routes. The presence of a

1,1-dichloro ethane metabolite in urine and expired air and its binding to tissue macromolecules provide

evidence of its absorption. Stu dies regarding the direct analysis of the extent and rate of

1,1-dichloroethane absorption are lacking and would provide useful information on the potential health

hazards associated with exposure to 1,1-dichloroethane via inhalation of contaminated air or ingestion of

contaminated water.

Studies in humans and animals regarding tissue distribution of 1,1- dichloroethane are not available. Its

lipophilicity suggests that the compound would be well absorbed and distributed to tissues according to

their lipid content. Binding studies conducted in rats following intraperitoneal injection indicate that

1,1- dichloroethane localizes in the liver, kidney, lung, and stomach. However, analysis has been limited

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to these tissues. Distribution studies using routes of administration relevant to human exposure

(inhalation, oral) would provide useful information on potential target organs of 1,1-dichloroethaneinduced toxicity in humans.

Characterization of 1,1

- dichloroethane's metabolism relies heavily on in vitro data

. These studies reveal

that the biotransformation process is mediated by cytochrome P-450 with hepatic microsomes being the

most effective. Identification of products in these microsomal studies allows for the prediction of

metabolic pathways. However, exposure to 1,1 -dichloroethane under in vivo conditions may alter

substrate availability and consequently alter the metabolic scheme. In vivo studies would provide a better

understanding of the rate and extent of 1,1- dichloroethane metabolism and a more r ealistic perspective of

its metabolic fate. This information would allow more accurate prediction of the potential of

1,1-dichloroethane to induce toxic effects, and aid in devising methods to detoxify exposed persons.

Studies regarding the excretion of 1,1

- dichloroethane by humans were not available. One study was

located in animals regarding the extent or rate of 1,1-dichloroethane excretion. Studies monitoring levels

in blood and excretion would be useful to estimate pharmacokinetic parameters.

Com parative Toxicokinetics. The absorption, distribution, metabolism, and excretion data for

1,1-dichloroethane are all derived from animal studies. It is likely that human disposition would follow a

scheme similar to that found in animals, but this concl usion is highly speculative. However, similar

results obtained in vivo across several animal species would provide supportive evidence for the

assumption that 1,1 -dichloroethane is handled in a similar manner in humans.

Methods for Reducing Toxic Effects

. Limited information regarding methods for reducing the

toxic effects of 1,1-dichloroethane were identified. Additional information regarding the toxicity of

1,1-dichloroethane is needed prior to research on mitigating the toxicity of this compound.

Children’s Susceptibility. Data needs relating to both prenatal and childhood exposures, and

developmental effects expressed either prenatally or during childhood, are discussed in detail in the

Developmental Toxicity subsection above.

No data were ide ntified on children’s susceptibility to the toxic effects of 1,1-dichloroethane and whether

there are toxicokinetic differences in the metabolism of this chemical between adults and children. As

noted previously, one developmental toxicity study (Schwetz et al. 1974) reported altered fetal growth.

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Child health data needs relating to exposure are discussed in Section 6.8.1, Identification of Data Needs:

Exposures of Children.

3.12.3 Ongoing Studies

N o ongoing studies sponsored by NIH, NTP, or EPA wer e identified for 1,1 -dichloroethane.

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### 4. CHEMICAL AND PHYSICAL INFORMATION

4.1 CHEMICAL IDENTITY

The synonyms, and identification numbers for 1,1- dich loroethane are listed in Table 4- 1

.

4.2 PHYSICAL AND CHEMICA L PROPERTIES

Important physical and chemical properties of 1,1- dich loroethane are listed in Table 4- 2

.

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### Table 4

- 1. Chemical Identity of 1,1

- Dichloroethane

Characteristic Information a Reference

Chemical nam e 1,1

- Dichloroethane b

Synonym(s) Alpha,alpha

- dichloroethane; asymmetrical dichloroethane;

S- dichloroethene; Dutch oil; ethane, 1,1

- dichloro

- ; ethylidene chloride; ethylidene dichloride; 1,1

- ethylidene dichloride c

Registered trade name(s) No data

Chemica l formula C2H4Cl2 b

Chemical structure 

### Cl H

Cl C C H

H H

Identification numbers:

CAS registry 75

- 34

- 3 b

NIOSH RTECS KI0175000

EPA hazardous waste U076

OHM/TADS No data

DOT/UN/NA/IMDG shipping DOT 2362; UN 2362; IMO 3.2

HSDB 64

NCI C04 535 d

a All information obtained from HSDB 2012, except where noted

b O’Neil et al

. 2006

c Archer 1978; Weiss 1986

d ChemIDPlus Lite 2012

CAS = Chemical Abstracts Service; DOT/UN/NA/IMDG = Department of Transportation/United Nations/North

America/Internation al Maritime Dangerous Goods Code; EPA = Environmental Protection Agency;

HSDB = Hazardous Substances Data Bank; NCI = National Cancer Institute; NIOSH = National Institute for Occupational Safety and Health; OHM/TADS = Oil and Hazardous Materials/Technical Assistance Data System; RTECS = Registry of Toxic Effects of Chemical Substances

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### Table 4

- 2. Physical and Chemical Properties of 1,1

- Dichloroethane

Property Information Reference

Molecular weight 98.97 HSDB 2012

Color Colorle ss Physical state Oily liquid O’Neil et al

. 2006

Melting point

- 96.9 °C HSDB 2012

Boiling point 57.3 °C O’Neil et al

. 2006

Density at 20 °C 1.175 g/cm 3 HSDB 2012

Odor Aromatic ethereal; chloroform

- like

Odor threshold:

Water No data

Air 120 p pm; 200 ppm Verschueren 1983

Solubility:

Water at 20 °C 0.55 g/100 g HSDB 2012

Organic solvents Miscible with oxygenated and chlorinated

solvents

Partition coefficients:

Log K

ow 1.79 HSDB 2012

Log K

oc 1. 48 HSDB 2012

Vapor pressure at 25 °C 230 mmHg HSDB 2012

Henry's law constant at 24 °C 5.62x10 - 3 atm

- m 3 /mol HSDB 2012

5.51x10 -3 atm

- m 3 /mol Chen et al. 2012

Autoignition temperature 457.8 °C HSDB 2012

Flashpoint Closed cup

- 12 °C; open cup 14 °C HSDB 2012

Flammability limits Lower 5.4%; up per 11.4% HSDB 2012

Conversion factors 1 ppm x 4.05 = 1 mg/m 3
1 mg/m 3 x 0.25 = 1 ppm

Explosive limits Lower explosive limit: 5.6%; moderate HSDB 2012 explosion hazard when exposed to heat or

flame

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

5.1 PRODUCTION

T able 5

- 1 lists the number of facilities in each state that manufacture or process 1,1

- dichlor oethane, the

activities and uses, and the range of maximum amounts of 1,1- dichloroethane that are stored on site. The

data listed in Table 5 -1 are derived from the Toxics Release Inventory (TRI10 2012). Based on the TRI

information from 2010, there are 204 facilities that produce or process 1,1-dichloroethane in the United

States. The TRI data should be used with caution since only certain types of facilities were required to

report. This is not an exhaustive list.

1,1-Dichl oroethane is produced commercially through the reaction of hydrogen chlo ride and vinyl

chloride at 20 –55 °C in the presence of an aluminum, ferric, or zinc chloride catalyst (HSDB 2012).

Other production methods include the direct chlorination of ethane, addition of hydrogen chloride to

acetylene, the reaction of ethylene and chlorine in the presence of calcium chloride, and the reaction of

phosphorus chloride and acetaldehyde (HSDB 2012). 1,1-Dichloroethane can also be produced as a

byproduct during the manufacture of chloral, as a byproduct in the production of vinyl chlori de via

ethylene oxychlorination (HSDB 2012; Marshall 2003), and as an intermediate in the production of

1,1,1-trichloroethane by thermal or photochemical chlorination of vinyl chloride (Cowfer 2006). It has

been reported that 1,1- dichloroethane often occu rs as an unwanted byproduct in numerous chlorination

and oxychlorination processes of C2 hydrocarbons (HSDB 2012).

Information regarding the production volume of 1,1-dichloroethane in the United States is not reported in

SRI Directory of Chemical Producers (SRI 2011). Additionally, no data are reported for U.S. production

volume in the Hazardous Substance Data Bank (HSDB 2012).

According to EPA Inventory Update Rule (IUR) records, in 2006, two companies in the United States

produced 1,1- dichloroethane in 2006: Oxy Vinyls in La Porte, Texas and The Dow Chemical Company

in Plaquemine, Louisiana ( EPA 2010a). Both of these companies manufactured 1,1-dichloroethane

primarily to be used as an intermediate. Production volume data were not provided for each sp ecific

company. Aggregated national production volumes reported in 2006 were in the range of 500,000–

<1 million pounds ( EPA 2010a ).

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### Table 5

- 1. Facilities that Produce, Process, or Use 1,1

- Dichloroethane

Minimum Maximum

Number of amount on s ite amount on site

State a facilities in pounds b in pounds b Activities and uses c

AL 1 1,000 9,999 12

AR 8 1,000 99,999 12

CA 2 100 999 12

FL 1 10,000 99,999 12

KS 1 10,000 99,999 1, 4

KY 6 10,000 99,999 1, 3, 6

LA 102 0 9,999,999 1, 2, 3, 4, 5, 6, 10, 12, 13

MI 1 10,000 99,999 7, 12

MO 2 1,000 999,999 9, 12

MS 3 1,000 99,999 12

OH 12 100 9,999 12

PA 2 100 9,999 12

SC 1 100 999 12

TX 62 0 9,999,999 1, 2, 3, 4, 5, 6, 12, 13, 14

a Post office state abbreviations used.

b Amounts on site reported by facilitie s in each state.

c Activities/Uses:

1. Produce 6. Impurity 11. Chemical Processing Aid 2. Import 7. Reactant 12. Manufactur ing Aid 3. Onsite use/processing 8. Formulation Component 13. Ancillary/Other Uses

4. Sale/Distribution 9. Article Component 14. Process Impurity 5. Byproduct 10. Repackaging

Source: TRI10 2012 (Data are from 2010)

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5. PRODUCTION, IMPO RT/EXPORT, USE, AND DISPOSAL

5.2 IMPORT/EXPORT

N o information was found concerning U.S. imports and exports of 1,1-dichloroethane.

5.3 USE

T he largest individual use of 1,1- dichloroethane is as an intermediate in the manufacture of

1,1,1- trichloro ethane, and to a lesser extent, vinyl chloride and high vacuum rubber (Cowfer 2006; HSDB

2012; Marshall 2003). 1,1

- Dichloroethane also has limited use as a solvent for plastics, oils, and fats, and

is thus employed as both a cleaning agent and a degreaser ( O’Neil et al . 2006). In the past, 1,1-dichloroethane was used as an anesthetic (HSDB 2012; O’Neil et al . 2006). Other uses of 1,1-dichloroethane

include fabric spreading, var nish and finish removers, organic synthesis, ore flotation, and as a fumigant

and insecticide spray (HSDB 2012). 1,1- Dichloroethane is also used in the manufacture of plastic wrap,

adhesives, and synthetic fiber (USGS 2006a ). No information is available regarding the use proportions

among these categories.

5.4 DISPOSAL

1,1- Dichloroethane may be disposed of by atomization within a combustion chamber equipped with an

appropriate effluent gas cleaning device, by high -temperature incineration with a hydrochloric acid

scrubber, or by placing product residues and sorbent media into 17H epoxy-lined drums and disposing of

them at an EPA

- approved site. However, the criteria for treatment or sanitary landfill disposal practices

are currently undergoing revisio n. Waste water treatment technologies investigated by the EPA include

concentration processes such as stripping, solvent extraction, activated carbon, and resin adsorption.

Consultation with environmental regulatory agencies is advised (HSDB 2012; Marsha ll 2003; NIOSH

1978 ).

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### 6. POTENTIAL FOR HUMAN EXPOSURE

6.1 OVERVIEW

1,1- Dichloroethane has been identified in at least 673 of the 1,699 hazar dous waste sites that have been

proposed for incl usion on the EPA National Priorities List (NPL) (HazDat 2007). However, the number

of sites evaluated for 1,1-dichloroethane is not known. The frequency of these sites can be seen in

Figur e 6-1

.

1,1- Dichloroethane in the environment is mainly related to the production, storage, consumption,

transport, and disposal of 1,1

- dichloroethane used as a chemical intermediate, solvent, finish remover, and

degreaser. In addition, 1,1-dichloroethane may occur in the environment as a biodegradation product of

1,1,1- trichloroethane. Releases from industrial processes are almost exclusively to the atmosphere.

Releases of the compound to surface waters and soils are expected to partition rapidly to the atmosphere

through volatilization. Hydrolysis, photolysis, and biodegradation do not appear to be important

processes in determining the environmental fate of 1,1- dichloroethane. It has been detected at generally

low levels in ambient air, surface water, groundwater, drinking water, and human breath. Concentrations

in environmental media are greatest near source areas (e.g., industrial point sources, hazardous waste

sites).

Inhalation of 1,1 -dichloroethane in ambient or workplace air is generally the main route of human

exposure to the compound. Estimates of populations potentially exposed to 1,1-dichloroethane in

workplace environments in the 1980s ranged from 715 to 1,957 workers (EPA 2001c). Ingestion of

contaminated drinking water may also be an important route of exposure for populations living near

industria l facilities and hazardous waste sites. Boman and Maibach (1996) concluded that exposure to

skin results in very little absorption due to the compound’s volatility; in addition, the levels greatly

diminish in properly ventilated areas.

6.2 RELEASES TO THE ENVIRONMENT

T he Toxics Release Inventory (TRI) data should be used with caution because only certain types of

facilities are required to report (EPA 2005). This is not an exhaustive list. Manufacturing and processing

facilities are required to repo rt information to the TRI only if they employ 10 or more full- time

employees; if their facility is included in Standard Industrial Classification (SIC) Codes 10 (except 1011,

1081, and 1094), 12 (except 1241), 20–39, 4911 (limited to facilities that combus t coal

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### Figure 6-1. Frequency of NPL Sites wi th 1,1-Dichloroethane Contamination

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6. POTENTIAL FOR HUMAN EXPOSURE

and/or oil for the purpose of generating electricity for distribution in commerce), 4931 (limited to

facilities that combust coal and/or oil for the purpose of generat ing electricity for distribution in

commerce), 4939 (limited to facilities that combust coal and/or oil for the purpose of generating

electricity for distribution in commerce), 4953 (limited to facilities regulated under RCRA Subtitle C, 42

U.S.C. section 6921 et seq.), 5169, 5171, and 7389 (limited S.C. section 6921 et seq.), 5169, 5171, and

7389 (limited to faciliti es primarily engaged in solvents recovery services on a contract or fee basis); and

if their facility produces, imports, or processes ≥25,000 pounds of any TRI chemical or otherwise uses

>10,000 pounds of a TRI chemical in a calendar year (EPA 2005).

Sect ion 112 of the Clean Air Act (CAA) lists 1,1-dicloroethane as one of 188 hazardous air pollutants

(HAPs) known to cause or suspected of causing cancer or other serious human health effects or ecosystem

damage (EPA 2000). EPA's National Emission Inventory (NEI) database contains data regarding sources

that emit criteria air pollutants and their precursors, and HAPs for the 50 United States, Washington DC,

Puerto Rico, and the U.S. Virgin Islands (prior to 1999, criteria pollutant emission estimates were

mai ntained in the National Emission Trends [NET] database and HAP emission estimates were

maintained in the National Toxics Inventory [NTI] database). The NEI database derives emission data

from multiple sources including: state and local environmental agencies; the TRI database; computer

models for on -road and off- road emissions; databases related to EPA's Maximum Achievable Control

Technology (MACT) programs to reduce emissions of hazardous air pollutants

. Using composite data

from the NTI database from 1990 to 1993, it was estimated that the annual emissions of 1,1-dichloroethane in the United States was approximately 274 tons per year during that time frame (EPA 2000).

Data downloaded from the 2005 NEI indicated that the total emission of 1,1-dichloroet hane was

approximately 387 tons, with the biggest source arising from point source waste disposal (EPA 2012d ).

There are no known natural sources of 1,1-dichloroethane. It has been reported that 1,1,1-trichloroethane

is rapidly biodegraded in anaerobic methanogenic environments, such as those found in landfills, to form

1,1-dichloroethane as the major product, with slow, yet complete anaerobic degradation of 1,1-dichloroethane to carbon dioxide also indicated (deBest et al . 1997; v an Eekert et al. 1999; Vogel and McCarty

1987). 1,1,1

- Trichloroethane occurs in the environment as a result of accidental spills, industrial

manufacturing, and use processes. Laboratory studies designed to elucidate the degradation reactions of

chloroethenes and chloroethanes have been described by Hallen et al. (1986) and Vogel and McCarty

(1987). Hallen et al. (1986) observed that dechlorination reactions appear to be reversible, and

chlorinated ethanes can be converted to chlorinated ethenes. Releases of 1,1

- dichloroetha ne to the

environment are a result of industrial manufacturing use processes and from the degradation of

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1,1,1- trichloroethane. Additional sources of environmental release are fugitive emissions from storage,

distribution, and disposal; use as an extraction solvent and fumigant or insecticide spray and in paints,

varnish, and paint removers; as a constituent of medicines and stone, clay, and glass products; and in ore

floatation (EPA 2001c; Infante and Tsongas 1982).

6.2.1 Air

E stimated releases of 8, 470 pounds (~ 3.84 metric tons) of 1,1-dichloroethane to the atmosphere from

14 domestic manufacturing and processing facilities in 2010, accounted for about 98.8% of the estimated

total environmental releases from facilities required to report to the TRI ( TRI10 2012). These releases are

summarized in Table 6

- 1

.

Emissions to the atmosphere comprise >98% of all releases of 1,1

- dichloroethane to the environment

(TRI10 2012). 1,1-Dichloroethane released in the production of 1,1,1- trichloroethane accounts for about

52% of the atmospheric releases, with the production of 1,2-dichloroethane accounting for about 35%.

Pellizzari (1982) reported the presence of low levels of 1,1- dichloroethane in ambient air of the Baton

Rouge industrial area and at the Kin

- Buc wa ste disposal site outside Edison, New Jersey. Eitzer (1995)

observed low levels of 1,1-dichloroethane (≤1 μg/m 3 ) in at least one of eight municipal solid waste sites

sampled in the United States.

Approximately 52,000 kg of 1,1- dichloroethane are released to the atmosphere by privately owned

treatment work facilities (POTWs) each year (EPA 1980).

In 2002, air emissions from point, area, and mobile sources in the Great Lakes region were calculated.

Data from Illinois, Indiana, Michigan, Minnesota, New York, Ontario, Pennsylvania, and Wisconsin were

evaluated. Total emissions of 1,1- dichloroethane in the Great Lakes region were calculated to be

27,110 pounds from point sources and 1,360 pounds from area sources. All states reported only point

source emiss ions for the compound with the exception of Minnesota, which reported 341 pounds from

point sources and 1,360 pounds from area sources. Ontario and Illinois accounted for the majority of the

emissions (41 and 33%, respectively). The other states each acc ounted for 1– 9% of the emissions (Great

Lakes Commission 2006).

1,1- Dichloroethane was detected in air samples at two current or former NPL hazardous waste sites where

it was detected in some environmental media (HazDat 2007).

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### Table 6

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

- Dichloroethane a

Reported amounts released in pounds per year b

Total release

State c RF d Air e Water f UI g Land h Other i On

- site j Off

- site k On

- and off

- site

KY 1 56 0 0 0 0 56 0 56

LA 7 8,186 72 0 9 0 8,258 9 8,267

OH 1 4 0 0 22 0 4 22 26

TX 4 223 3 0 0 0 226 0 226

Total 14 8,470 75 0 31 0 8,544 31 8,575

a The TRI data should be used with caution since only certain types of facilities are required to report. This is not an

exhaustive list. Data are rounded to nearest whole number.

b Data in TRI are maximum amounts released by each facility.

c Post office state abbreviations are used.

d Number of reporting facilities.

e The sum of fugitive and point source releases are included in releases to air by a given facility.

f Surface water discharges, waste water treatment

- (metals only), and publicly owned treatment works ( POTWs) (metal and metal compounds).

g Class I wells, Class II

- V wells, and underground injection.

h Resource Conservation and Recovery Act (RCRA) subtitle C landfills; other onsite landfills, land treatment, surface impoundments, other land disposal, other landfills.

i Storage only, solidification/stabilization (metals only), other off

- site management, transfers to waste broker for disposal, unknown
j The sum of all releases of the chemical to air, land, water, and underground injection wells.

k Total amount of chemical transferred off

- site, including to POTWs.

RF = reporting facilities; UI = underground injection

Source: TRI10 2012 (Data are from 2010)

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6.2.2 Water

E stimated releases of 75 pounds (~0.034 metric tons) of 1,1- dichl oroethane to surface water from

11 domestic manufacturing and processing facilities in 2010, accounte d for <1% of the estimated total

environmental releases from facilities required to report to the TRI (TRI10 2012). This estimation

includes surface water discharges, waste water treatment (metal only), and POTWs (metal and metal

compounds) (TRI10 2012). These releases are summarized in Table 6

- 1

.

Industrial releases of 1,1- dichloroethane to surface waters are minor in comparison to releases to the

atmosphere. Releases from solvent use and POTWs account for only 2,000 kg annually ( EPA 1982b ).

Industrial processes involving the use of 1,1- dichloroethane as a chemical intermediate or cleaning

solvent are believed to be the largest sources of surface water releases. Young et al. (1983) reported

1,1-dichloroethane in the primary, secondary, and final efflu ents from municipal wastewater treatment

plants. Approximately 1,000 kg of 1,1- dichloroethane are discharged in effluent from POTWs each year

(EPA 1980).

1,1- Dichloroethane was detected in groundwater samples at 106 current or former NPL hazardous waste

sites where it was detected in some environmental media (HazDat 2007). It was detected in surface water

at 27 current or former NPL hazardous waste sites where it was detected in some environmental media

(HazDat 2007).

6.2.3 Soil

E stimated releases of 31 pounds (~0.014 metric tons) of 1,1- dichl oroethane to soils from eight domestic

manufacturing and processing facilities in 2010, accounted for <0.5% of the estimated total

environmental releases from facili ties required to report to the TRI (TRI10 2012). These releases are

summarized in Table 6

- 1

.

Little information was found regarding releases of 1,1 -dichloroethane to soils. Solvent use and POTWs

are the only identified sources of 1,1-dichloroethane releases to the land, with 6,000 kg released in 1978

( EPA 1982b). Approximately 4,000 kg of 1,1-dichloroethane from POTWs are dispersed on land each

year as sludge (EPA 1980).

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1,1- Dichloroethane was detected in soil samples at 170 current or former NPL hazardous waste sites

where it was detected in some environmental media (HazDat 2007). It was detected in sediment at

37 current or former NPL hazardous waste sites where it was detected in some environmental media

(HazDat 2007).

6.3 ENVIRONMENTAL FATE

6.3.1 Transport and Partitioning

R eleases of 1,1

- dichloroethane to the environment as a result of industrial activity are expected to be

primarily to the atmosphere (see Section 6.2). 1,1- Dichloroethane rele ased to the atmosphere may be

transported long distances before being washed out in precipitation. For example, Pearson and

McConnell (1975) attributed the presence of chlorinated organic compounds, including 1,1-dichloroethane, in upland waters to long-range aerial transport and deposition in precipitation. EPA (1982b )

discussed the atmospheric fate of 1,1

- dichloroethane in the Gulf Coast area, where there is a high

percentage of cloudy days. Increased atmospheric losses due to washout in frequent, hea vy rains could

occur, although much of the 1,1- dichloroethane could be revolatilized. Dichloroethanes released in this

area could be transported north by the prevailing winds to populated areas before significant

photochemical degradation could occur.

Cu pitt (1980), however, considered the loss of 1,2-dichloroethane from the atmosphere by dissolution

into rain drops or adsorption onto aerosols insignificant compared with loss from chemical degradation

based on mathematical calculations. Since 1,1-dichloroethane has higher volatility and lower aqueous

solubility than the 1,2-isomer, physical removal of 1,1-dichloroethane from the atmosphere would be

even less likely to be important. Pellizzari et al. (1979) measured actual concentrations of airborne

contaminants in the vicinity of known emission sources of 1,1-dichloroethane, making aerial transport the

logical source of downwind concentrations.

The Henry's law constant value for 1,1- dichloroethane (5.51x10 -3 atm -m 3 /mol) suggests that it should

partition rapidly to the atmosphere. The evaporation half-life depends on a number of factors; wind speed

and mixing conditions of the receiving waters are particularly important. Dilling et al. (1975) and Dilling

(1977) estimated a volatilization half

- life of 22 minutes for 1,1-dichloroethane present at 1 ppm

concentration in an open water column held at 25 °C and stirred at 200 rpm. Under these conditions, 90%

of the compound was removed within 109 minutes. Volatilization half- lives determined in the laboratory

are related to actual environmental situations by a correction factor that takes into account the oxygen re

-

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6. POTENTIAL FOR HUMAN EXPOSURE

aeration rate ratio. The re-aeration rate ratio has been determined to be 0.55 for 1,1-dichloroethane

(Cadena et al. 1984). Using the values of Mabey et al. (1981) for oxygen re- aeration rates in ponds and

rivers (0.19 and 0.96 day -1 , respectively), the evaporation half -life of 1,1- dichloroethane is estimated to be

approximately 5 times longer for ponds than for rivers (>1 day for river water and >6 days for pond

water).

Little information was found regarding partitioning of 1,1-dichloroethane from the water column onto

sediments. According to DeWulf et al. (1996), 1,1- dichloroethane does not really accumulate on marine

sediment and it will ther efore not be an important sink for this compound. Analogs of the compound (i.e.,

dichloromethane, trichloromethane, and 1,1,1 -trichloroethane) have not been found to concentrate

selectively onto sediments (Dilling et al. 1975; Pearson and McConnell 1975). The K

oc values for these

compounds are similar to the K

oc for 1,1 -dichloroethane; therefore, partitioning to sediment from the

water column is not likely to be an important environmental fate process for 1,1-dichloroethane.

1,1- Dichloroethane released t o land surfaces in spills would rapidly volatilize to the atmosphere, but

1,1-dichloroethane remaining on soil surfaces would be available for transport into groundwater, since the

compound does not sorb to soil particulates unless the organic content of t he soil is high. Experimentally

derived K

oc values for a silt loam soil also indicate that little sorption of 1,1-dichloroethane to low organic

content soil is expected . Goodin and Webber (1992) conducted studies of several volatile organic

compounds (VO Cs), including 1,1

- dichloroethane, to determine their fate in soils. It was determined that

the compounds were lost from the soils mainly by volatilization, with first- order disappearance half

- lives

ranging from 1 to 949 hours. Wilson et al. (1981) found that although 50% of the applied 1,1-dichloroethane volatilized to the atmosphere, the remainder percolated rapidly through a sandy soil, suggesting

ready availability to groundwater transport processes. .

Gossett et al. (1983) analyzed the tissues of several species of aquatic organisms for 1,1 -dichloroethane

near the discharge of the Los Angeles County waste water treatment plant. The concentration of

1,1-dichloroethane in the effluent was 3.5 ppb; however, none was found in the animal tissues (dete ction

limit of 0.3 –0.5 ppb). These results may be evidence that the potential for 1,1- dichloroethane to

bioconcentrate is low in aquatic organisms. An estimated bioconcentration factor of 5 indicates that

bioconcentration would be low (HSDB 2012).

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6.3.2 Transformation and Degradation

6.3.2.1 Air

I n the atmosphere, 1,1-dichloroethane is oxidized by reaction with hydroxyl radicals. The rate constant

for the vapor -phase reaction is 2.74x10 -13 cm 3 /molecule-second at 25 °C (HSDB 2012). The residence

time of the compound in the atmosphere has been estimated to be 49 days (HSDB 2012).

6.3.2.2 Water

1,1- Dichloroethane in surface water is expected to be lost to the atmosphere through volatilization before

undergoing any significant chemical or biological degradation. The hydrolytic half-life of 1,1-dichloroethane at pH 7 and 25 °C has been estimated to be 60 years (Jeffers et al. 1989).

As summarized in Klecka et al. (1990), 1,1-dichloroethane is produced by biodegradation of

1,1,1- trichloroet hane in groundwater. Further degradation could also occur. In the absence of oxygen

and in the presence of anaerobic, methane -producing bacteria, halo carbons are transformed by reductive

dehydrohalogenation in a step -wise manner: 1,1,1-trichloroethane → 1,1-dichloroethane → chloroethane.

v an Eeker et al. (1999) reported 31.1% anaerobic degradation of 1,1-dichloroethane to mainly

chloroethane (14.5%) in living sludge after 25 days. Under aerobic conditions, Tabak et al. (1981)

reported about 50% degradation of 1,1-dichloroethane by unadapted microorganisms isolated from

municipal waste water inoculum after 7 days, which was increased to 78% degradation by adapted

organisms in the same time period. 1,1-Dichloroethane has been reported to be resistant to biological

degradation by bacteria isolated from shallow aquifer aerobic groundwater after 8–16 weeks incubation

(Wilson et al. 1983).

Data from landfi ll sites with a documented contamination history were examined by Cline and Viste

(1985). They observed that 1,1-dichloroethane was detected in groundwater at sites where the compound

had not been handled or disposed of and concluded that 1,1-dichloroethane had been produced by

anaerobic degradation of other compounds present, particularly 1,1,1-trichloroethane. Washington and

Cameron (2001) used well monitoring data, from a landfill with a contamination history, to calculate a

degradation rate constant for 1,1-dichloroethane. Under sulfate-reducing conditions at 10 °C, the rate

constant was found to be 6.0x10 -3 L/day with a half -life of 115 days.

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6.3.2.3 Sediment and Soil

1,1- Dichloroethane in soils is expected to volatilize to the atmosphere or be transported to groundwater

before undergoing significant abiotic transformation; the compound is not expected to sorb to soils of low

organic content. As in surface waters, direct photolysis of 1,1

- dichloroethane on soil surfaces is not

expected. The rat e of biodegradation of 1,1-dichloroethane in soils is unknown. In subsurface soil, the

loss of 1,1

- dichloroethane through biodegradation is expected to be insignificant (Wilson et al. 1983).

The biodegradation half-life of 1,1,1- trichloroethane under ana erobic conditions has been reported to be

about 16 days, whereas the half-life of 1,1- dichloroethane has been reported to be >30 –60 days (Wood et

al. 1985).

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT

R eliable evaluation of the potential for human exposure to 1,1- dichloroethane depends in part on the

reliability of supporting analytical data from environmental samples and biological specimens.

Concentrations of 1,1-dichloroethane in unpolluted atmospheres and in pristine surface waters are o ften

so low as to be near the detection limits of analytical methods. In reviewing data on 1,1-dichloroethane

levels monitored or estimated in the environment, it should also be noted that the amount of chemical

identified analytically is not necessarily equivalent to the amount that is bioavailable. The analytical

methods available for monitoring 1,1-dichloroethane in a variety of environmental media are detailed in

Chapter 7.

1,1-Dichloroethane has been detected in ambient urban and rural air, in waste gas generated from garbage

dumps, and in surface water, groundwater, and drinking water. Quantitative concentration information is

presented in the following sections by environmental medium.

6.4.1 Air

1,1- D ichloroethane was not seen at a detection limit of 5 ppt in ambient rural air samples taken in

southeastern Washington state (Grimsrud and Rasmussen 1975). It has been found at higher

concentrations in ambient air samples from urban areas of the United States. EPA (1983b ) tabulated

atmospheric l evels at urban, rural, and industrial sites across the United States and reported a median

concentration of 55 ppt. Pellizzari (1982) reported the detection of low levels (unspecified

concentrations) of the compound in the vicinity of the Baton Rouge indu strial area. EPA (1983a )

reported that the average concentration of the compound in the air of seven urban locations in 1980–1981

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6. POTENTIAL FOR HUMAN EXPOSURE

ranged from 0.1 to 1.5 ppb. It has also been detected in samples of ambient air collected in the vicinity of

hazardous waste disposal sites, such as the Kin

- Buc site near Edison, New Jersey, at a level of 23 μg/m 3

(5.68 ppm) (Pellizzari 1982). EPA (1978) tabulated analytical results for 1,1

- dichloroethane in the

ambient air of various locations generally in close proximity to industrial plants, including Magna, Utah

(0.082 ppb); Iberville, Louisiana (0.12 ppm); Deer Park, Texas (0.14 ppb); and Baton Rouge (0.058 ppb)

and Geismar, Louisiana (0.14 ppb).

Barkley et al. (1980) found no 1,1-dichloroethane in the ambient air surrounding nine houses bordering

the old Love Canal. Gupta et al. (1984) found 1,1- dichloroethane at higher levels indoors (mean

concentration of 3.2 ppb) than outdoors (not detected) in residences in suburban Knoxville, Tennessee,

and concluded that there must be a source of the compound inside the home. Possible sources were not

identified except to suggest building materials or chlorinated water.

Air monitoring data from 22 tire fire incidents across the United States were evaluated. 1,1 -Dichloroethane was detected at low levels in the vicinity of several of the fires. It was noted that the source may

be from something other than the burning tires (EPA 1993).

Air was monitored over a 3-week period at the Fresh Kills Landfill of Staten Island, New York. The

overall air emission rate for 1,1 -dichloroethane was 0.216 g/second (EPA1996a ).

In 1994, 1,1-dichloroethane was not detected in six spatial sites around the Columbus metro area.

Detection limits of the analysis were 0.05 ppb (Spicer 1996).

In 1996, Mohamed et al. (2002) monitored VOCs in air at 13 urban locations in the United States for

1 year. Monitoring sites were located in Louisiana, Texas, Vermont, and New Jersey. TRI reporting

facilities near the monitoring sites ranged from 0 to 38 faciliti es. 1,1- Dichloroethane was detected at all

13 of the monitoring stations at levels <1 ppb by volume (ppbv). The detection limit of the analytical

method was <0.5 ppbv.

1,1-Dichloroethane was detected in the headspace of five out of eight household bleach products at levels

ranging from 0.7 to 176 μg/m 3 . It was concluded that the compound was formed by the reaction of

hypochlorite and the organic matter of the product’s additives. In addition, 1,1- dichloroethane levels of

indoor air increased during the use of bleach products, from 0.004– 0.01 μg/m 3 before use, to 0.01–

0.62 μg/m 3 during use, and then to 0.01– 0.29 μg/m 3 after use (Odabasi 2008).

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6.4.2 Water

EPA ( 1982b ) summarized data from EPA's STORET database, where reported concentrations of

1,1-dichloroethane range from undetected (<10 ppb) to 1,900 ppb, with the highest reading in the Upper

Mississippi River basin at Alton, Illinois. However, they observed that monitoring results reported for

1,1- dichloroethane in surface waters are almost always below the detection limit (generally 10 ppb). The

compound has also been found in samples of urban runoff from Long Island, New York, and Eugene,

Oregon, at concentrations of 1.5 and 3 ppb, respectively (Cole et al. 1984). Coniglio et al. (1980)

summari zed groundwater monitoring data obtained by numerous state agencies and reported that

1,1-dichloroethane was found in 18% of the wells tested, with a maximum concentration of 11,330 ppb.

They cautioned that the state data may have been biased since the m onitoring was generally conducted by

the states in areas where contamination was suspected. However, 1,1 -dichloroethane has been detected in

groundwater sampled during random testing of water supplies (see further discussion).

Finished water supplies obt ained from groundwater sources were tested by EPA for contaminants. It was

reported that up to 10.8% of 158 nonrandom sample sites from across the United States contained

detectable levels of 1,1- dichloroethane. The maximum concentration was 4.2 ppb (Westrick et al. 1984).

Drinking water samples from a number of urban and rural locations in the United States have been

reported to be contaminated with 1,1- dichloroethane. Unspecified levels of the compound have been

detected in drinking water samples ta ken from Philadelphia (Suffet et al. 1980). Private drinking water

wells in Wisconsin were found to contain unspecified levels of 1,1 -dichloroethane in 11 of 617 wells

surveyed (Krill and Sonzogni 1986). Concentrations of 1–3 ppb were reported in four public well water

supplies in Iowa (EPA 1985b ).

Groundwater samples taken from 178 hazardous waste disposal sites were found to contain 1,1-dichloroethane at 18% frequency (Plumb 1987), with an average concentration of 0.31 ppm and a maximum

concentration of 56.1 ppm (Yang and Rauckman 1987). Using the STORET database, Staples et al.

(1985) reported median concentrations of <0.1 ppb in 8,716 samples of ambient water (3% detectable

values), <1.0 ppb in 1,375 effluent samples (5% detectable values), <5.0 ppb in 354 sediment samples

(0.6% detectable values), and <0.05 ppb in 94 biota samples (no detectable values). Also using the

STORET database, EPA (1982b ) reported that 1,1 -dichloroethane was not found in the sediment of the

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6. POTENTIAL FOR HUMAN EXPOSURE

lower Mississippi or the western Gulf of Mexico; however, a maximum concentration of 5 ppb was

detected in sediment samples from the Pacific Northwest.

Nine shallow groundwater sa mples contained 1,1 -dichloroethane with a maximum concentration of

2.2 μg/L, in 5.3% of 208 urban wells sampled in the United States (Kolpin et al. 1997).

1,1-Dichloroethane was detected above background levels in groundwater beneath Savannah River Site’s

Interim Sanitary Landfill. Several wells at the site were sampled twice each in 2005. The site was in

operation from 1992 to 1998 (DOE2005).

The Aerojet

- General Corporation reports that 1,1 -dichloroethane is present as a groundwater contaminant

just ou tside Sacramento, California, in varying concentrations in several separate domestic and industrial

well water samples and test borings. Additionally, a 1996 study indicated the presence of the compound

in groundwater from the Glassboro region of Southern New Jersey at a detection frequency of 5% and a

concentration of >0.1 μg/L (HSDB 2012).

The Solid Waste Management Unit 12 in South Carolina was in use from the 1970s until 1981. In

September 1999, water sampled from an excavation hole that contained a leaking underground storage

tank (UST) contained 1,1-dichloroethane at a concentration of 84,300 μg/L. Monitoring efforts of wells

surrounding the site from August 2000 to November 2007 detected 1,1-dichloroethane as a consistent

contaminant in the groundwater. Groundwater samples from August 2001 indicated that the highest

concentrations of contaminants in groundwater were near the UST, indicating that it was the source area.

Maximum measured concentrations of 1,1-dichloroethane of 155,000 μg/L were fou nd at that time.

Natural and engineered remediation efforts have contributed to the irregular decline of contaminants. On

the northern side of the facility, concentrations of 1,1-dichloroethane in groundwater at one of the wells

declined from >100 μg/L in 2000 to approximately 20–30 μg/L in 2003, remained relatively unchanged in

2003–2005, and declined in 2006–2007 (USGS 2006b ).

The National Water Quality Assessment Program (NAWQA) evaluated 3,496 wells nationwide for the

presence of VOCs from 1985 to 2001. 1,1-Dichloroethane had an overall detection frequency of 0.86% at

an assessment level of 0.2 μg/L; a detection frequency of 0.17% at an assessment level of 1 μg/L; and a

detection frequency of 0.029% at an assessment level of 5 μg/L. The compound was also detected as a

mixture with 1,1,1-trichloroethane in 0.71% of the samples (USGS 2006a). According to the report, there

were 30 detections of 1,1- dichloroethane in 3,496 aquifer samples. More specifically, 7 detections

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occurred in 2,400 domestic well samples, 22 detections occurred in 1,096 public well samples,

20 detections occurred in 847 urban area shallow groundwater samples, and 1 detection occurred in

723 agricultural area shallow groundwater samples. Reported concentrations ranged from approxi mately

0.007 to 9 μg/L, with the bulk of the samples falling in the range of 0.02– 0.2 μg/L (USGS 2006a).

From May 3, 1999 through October 23, 2000, random samples from 954 water sources across the United

States were collected. The sources included 579 g roundwater and 375 surface water samples.

1,1-Dichloroethane was detected in 11 groundwater samples at levels between 0.1 and 10 μg/L (USGS

2003).

The CALEPA (2003) a nalys is of 13,347 California groundwater sources of drinking water found

1,1-dichloroetha ne in 68 samples, ranging from 0.51 to 30 ppb. 1,1-Dichloroethane was not found in any

of the 754 surface water sources of drinking water sampled.

Samples from 2,948 wells across the United States were sampled between 1985 and 1995. The sources

consiste d of both drinking water and non-drinking water in 406 urban wells and 2,542 rural wells. The

detection frequency of 1,1 -dichloroethane was 6.4% in urban wells and 0.7% in rural wells. Reported

concentrations were approximately 0.2 –60 μg/L with a median of approximately 0.45 μg/L, and

approximately 0.2–8 μg/L with a median of about 0.7 μg/L, respectively (Squillace et al. 1999).

6.4.3 Sediment and Soil

V ery little information was found on the ambient concentrations of 1,1-dichloroethane in soil, or o n the

current disposal of waste products containing the compound in landfills. 1,1- Dichloroethane was

detected, yet not quantified, in soil samples of Love Canal, New York. At a detection limit of 0.5 ppb,

1,1- dichloroethane was not detected in sediment of the submarine outfall region of the Los Angeles

County (Joint Water Pollution Control Plant [JWPCP]) municipal waste water treatment plant (HSDB

2012). The compound has more commonly been detected in ambient air and groundwater samples taken

at hazardo us waste sites, and it is expected that the lack of available soil monitoring data is at least in part

due to rapid partitioning of 1,1- dichloroethane released to soils to these other media.

6.4.4 Other Environmental Media

L ittle information was found on the levels of 1,1-dichloroethane in other media. Ferrario et al. (1985)

measured 33 ppb wet weight of 1,1- dichloroethane in oysters from Lake Pontchartrain near New Orleans,

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Louisiana; however, 1,1- dichloroethane was not detected in two types of clams . Kallonen et al. (1985)

detected 1,1-dichloroethane in the effluent gases of burning polyester fiber fill. Data on concentrations in

human breath are presented in Section 6.5. 1,1-Dichloroethane was not found in any samples in a survey

of 234 table

- ready foods evaluated for the presence of VOCs (Heikes et al. 1995). Page and Lacroix

(1995) found 1,1-dichloroethane in three peanut butter samples at levels of 1.1, 1.9, and 3.7 μg/kg;

however, the compound was not found in several other foods that were an alyzed.

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE

T he greatest source of exposure to 1,1-dichloroethane for most of the U.S. population is inhalation of the

compound in contaminated air, especially near source areas. Another potential route of human exposure

is ingestion of the compound in contaminated drinking water, and use of consumer products that may

contain 1,1-dichloroethane. Occupational exposure to 1,1- dichloroethane may occur via inhalation or

dermal contact at workplaces where it is produced or used (HSDB 2012).

The National Occupational Hazard Survey (NOHS), conducted by NIOSH from 1972 to 1974, estimated

that 715 workers in 143 plants were potentially exposed to 1,1-dichloroethane in the workplace in 1970

(NIOSH 1976). These esti mates were derived from observations of the actual use of 1,1 -dichloroethane

(90% of total estimate) and the use of trade name products known to contain 1,1-dichloroethane (10%).

The exposed workers were in the rubber and plastic, chemical and allied prod ucts, electrical equipment

and supply, medical and other health services, miscellaneous business services, and oil and gas extraction

industries. The occupational groups with exposed workers were assemblers, agricultural and biological

technicians, chemis ts, electrical and electronic engineering technicians, therapists, geologists, and

machine operators.

Preliminary data from a second workplace survey, the National Occupational Exposure Survey (NOES),

conducted by NIOSH from 1980 to 1983, indicated that 1,957 workers, including 272 women, were

potentially exposed to 1,1-dichloroethane in the workplace in 1980 (NIOSH 1984). The exposed workers

were employed in the chemical and allied products and business service industries, as chemical

technicians; plumbers, pipefitters, and steamfitters; supervisors in production occupations; electricians;

machinists; chemical engineers; and welders and cutters. The estimates were based on direct observation

by the surveyor of the actual use of the compound (100%).

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Neit her the NOHS nor the NOES databases contain 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.

NIOSH (1978) noted that there was a large potential for exposure to 1,1- dichloroethane in the workplace

during its use as a dewaxer of mineral oils, extractant for heat -sensitive substances, or fumigant, and in

the manufacture of vinyl chloride and high-vacuum rubber and silic on grease.

The EPA (1982) and Wallace et al. (1982) conducted a study of the levels of 1,1- dichloroethane in the

inhaled and exhaled air and drinking water of college students in Texas and North Carolina. Low levels

(<0.49 ppb) of 1,1

- dichloroethane were found in the personal air quality monitors of the Texas students,

whose campus bounded a petrochemical manufacturing area, but none was detected in the exhaled breath

samples. 1,1-Dichloroethane was not detected in the breathing zone air of the North Car olina students.

Barkley et al. (1980) found a trace of 1,1- dichloroethane in the expired breath of one resident whose

home bordered the old Love Canal, but none was detected in ambient air. Wallace et al. (1984) found a

trace of 1,1- dichloroethane in the expired breath and drinking water of one resident of New Jersey).

Assuming a median ambient air level of 55 pptv reported by EPA (1983b ) and a theoretical average

inhalation of 20 m 3 air/day, the average inhalation exposure to 1,1-dichloroethane for an i ndividual in the

United States is estimated at 4 μg/day.

Buckley et al. (1997) reported the detection of 1,1-dichlorethane in 1 of 16 blood samples at a

concentration of 0.01 μg/L. 1,1-Dichloroethane was detected in <10% of blood samples from

1,000 people between the years 1988 and 1994 (Needham et al. 1995). In October 2001, Edelman et al.

(2003) analyzed blood and urine samples from World Trade Center firefighters for V OCs, including

1,1-dichloroethane; detection of the compound was insignificant. A National Health and Nutrition

Survey of the U.S. population in 2003–2004 screened for 1,1-dichloroethane in blood samples at a limit

of detection (LOD) concentration of 0.01 ng/mL ( CDC 2009). Th e samples were taken from

1,367 participants in the age range of 20 –59 years old, about half females (n=679) and half males

(n=670). The survey included Mexican Americans (n=267), non-Hispanic blacks (n=300), and nonHispanic whites (n=695). The portion of the data below the LOD for 1,1-dichloroethane was too high to

provide valid results ( CDC 2009).

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6.6 EXPOSURES OF CHILDREN

This section focuses on exposures from conception to maturity at 18 years in humans. Differences from

adults in susceptibility to hazardous substances are discussed in Section 3.7, Childr en’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 proportio n 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 1,1-dichloroethane in children.

1,1-Dichloro ethane has been detected in air, as discussed in Section 6.4. 1, and inhalation of contaminated

air likely represents the greatest route of potential exposure for children. 1,1-Dichloroethane has also

been detected in drinking water, and therefore, ingestion of contaminated water is a possible source of

exposure. Dichloroethane (isomer not specified) has been detected in human milk (Urusova 1953);

however, these data are not current.

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES

H uman exposure to 1,1-dichloroethane is expected to be highest among certain occ upational groups (e.g.,

chemical and allied products industry workers) and members of the general population living in the

vicinity of industrial point emission sources (EPA 2001c) and hazardous waste sites. The compound has

been detected in both ambient air and water in low concentrations, with substantially higher

concentrations in localized areas around industrial and disposal sites. No information was found

regarding the number of people potentially exposed around hazardous waste sites.

6.8 ADEQUAC Y OF THE DATABASE

S ection 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 effe cts of 1,1- dichloroethane is available. Where adequate

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6. POTENTIAL FOR HUMAN EXPOSURE

information is not available, ATSDR, in conjunction with NTP, is required to assure the initiation of a

program of research designed to determine the health effects (and techniques for developing meth ods to

determine such health effects) of 1,1-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 m et 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

P hysical and Chemical Properties. The physical/chemical properties of 1,1-dichloroethane are

sufficiently well characterized to enable assessment of the envi ronmental fate of this compound.

Production, Import/Export, Use, Release, and Disposal. According to the Emergency

Planning and Community Right- to -Know Act of 1986, 42 U.S.C. Section 11023, industries are required

to submit substance release and off

- si te transfer information to the EPA. The TRI, which contains this

information for 2010, became available in February of 2012. This database is updated yearly and should

provide a list of industrial production facilities and emissions.

Based on its indust rial use, 1,1

- dichloroethane is primarily released to the atmosphere, and humans are

potentially exposed to this chemical through the inhalation or ingestion of contaminated air or water.

However, because the data available on production, import, export, use, and disposal are limited, it is

difficult to estimate whether or not the potential for human exposure to 1,1-dichloroethane may be

substantial. Data concerning the production and use of 1,1-dichloroethane both within the United States

and worldwide are extremely limited. Information regarding possible disposal methods, criteria, and

regulations are available; however, the present criteria may undergo revision in the near future.

Information on current production levels, quantities imported and expor ted, proportions allocated to

various uses, and proportions and efficiencies associated with differing modes of disposal is limited. This

information would be useful in identifying potential sources and levels of exposure, thus enabling

identification of exposed populations.

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6. POTENTIAL FOR HUMAN EXPOSURE

Environmental Fate. Releases from industrial processes are almost exclusively to the atmosphere,

and releases of the compound to surface waters and soils are expected to partition rapidly to the

atmosphere through volatilization. 1,1

- Dichloroethane released to the atmosphere may be transported

long distances before being washed out in precipitation. Although 1,1- dichloroethane released to land

surfaces in spills would rapidly volatilize to the atmosphere, the 1,1 -dichloroethane remaining on soil

surfaces would be available for transport into groundwater. The atmospheric residence time of

1,1-dichloroethane is about 44 days. The dominant removal mechanism is reaction with hydroxyl free

radicals. Hydrolysis and biodegradation do not appear to be important processes in the environmental

fate of this compound. Data are lacking on the partitioning of 1,1- dichloroethane from the water column

onto sediments. Additional information on the atmospheric transformation and on the rate of

biodegradation of 1,1-dichloroethane in soils would be useful in the determination of its environmental

fate.

Bioavailability from Environmental Media. Data are incomplete on the bioavailability of

1,1-dichloroethane from environmental media. Animal d ata on 1,1 -dichloroethane exposure via

inhalation and oral administration in drinking water suggest that the compound is bioavailable following

inhalation of ambient air and ingestion of drinking water. Additional information on the bioavailability of

1,1-dichloroethane from air, water, soil, and sediment would be useful in determining actual risks

associated with exposure to environmental levels of 1,1 -dichloroethane.

Food Chain Bioaccumulation. The information located on the potential for bioconcentration of

1,1- dichloroethane in plants, aquatic organisms, or animals is limited. An analysis of animal tissues from

several species of aquatic organisms near the discharge of a waste water treatment plant did not detect

1,1- dichloroethane in the animal ti ssues, although the compound was found in the effluent. However,

1,1-dichloroethane has been detected in oysters (33 ppb wet weight). An estimated bioconcentration

potential of <1 from the K

ow suggests that bioconcentration would not be expected. Very l ittle

information was found regarding the biomagnification of 1,1-dichloroethane among food chain trophic

levels. Additional information on bioconcentration and biomagnification would be useful in determining

whether food chain bioaccumulation is an impor tant source of human exposure.

Exposure Levels in Environmental Media. Reliable monitoring data for the levels of

1,1- dichloroethane in contaminated media at hazardous waste sites are needed so that the information

obtained on levels of 1,1-dichloroethane in the environment can be used in combination with the known

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6. POTENTIAL FOR HUMAN EXPOSURE

body burden of 1,1-dichloroethane to assess the potential risk of adverse health effects in populations

living in the vicinity of hazardous waste sites.

Limited information is available rega rding ambient concentrations of 1,1- dichloroethane in soils. Based

on a median ambient air level reported in 1982, the average inhalation expos ure to 1,1

- dichloroethane for

an individual in the United States has been estimated to be 4 μg/day. The information on foodstuffs is

limited to the detection of 1,1 -dichloroethane in oysters (33 ppb wet weight). Additional site- specific

concentration dat a for ambient air, drinking water, soil, and biota would be helpful in estimating potential

exposure of the general population as well as populations in the vicinity of hazardous waste sites.

Exposure Levels in Humans. Although relatively recent esti mates of the size of the population

occupationally exposed to 1,1 -dichloroethane are available from NIOSH, monitoring data on workplace

exposures are generally limited, with a few observations about 1,1 -dichloroethane included in detailed

studies of 1,2 -dichloroethane. A study of the levels of 1,1- dichloroethane in the inhaled and exhaled air

and drinking water of college students in Texas and North Carolina found low levels (<0.49 ppb) of

1,1-dichloroethane in the personal air quality monitors of the Texas students, whose campus bounded a

petrochemical manufacturing area, but none in samples of their exhaled breath. Additional information

on the availability of biomarkers that could be used to indicate human exposure to 1,1 -dichloroethane

would be helpful

.

This information is necessary for assessing the need to conduct health studies on these populations.

Exposures of Children. A data need has been identified to conduct body burden studies of

1,1- dichloroethane in children. Measurements of 1,1

- dichlo roethane in blood samples for a population of

adults was conducted in 2003–2004 as part of the National Health and Nutrition Examination Survey

(CDC 2009). Most of the samples were below the detection limit of 0.01 ng/mL. Similar results among a

group of children would demonstrate that exposure to 1,1 -dichloroethane is low for both children and

adults.

Child health data needs relating to susceptibility are discussed in Section 3.12.2, Identification of Data

Needs: Children’s Susceptibility.

Exposure Re gistries. No exposure registries for 1,1

- dichloroethane were located. This substance is

not currently one of the compounds for which a sub- registry has been established in the National

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6. POTENTIAL FOR HUMAN EXPOSURE

Exposure Registry. The substance will be considered in the future when chemical selection is made for

sub- registries to be established. The information that is amassed in the National Exposure Registry

facilitates the epidemiological research needed to assess adverse health outcomes that may be related to

exposure to th is substance.

6.8.2 Ongoing Studies

No ongoing studies regarding sponsored by NIH or EPA were identified for 1,1-dichloroethane.

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6. POTENTIAL FOR HUMAN EXPOSURE



### This page is intentionally blank.

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### 7. ANALYTICAL METHODS

The purpose of this chapter is to descr ibe the analytical methods that are available for detecting,

measuring, and/or monitoring 1,1-dichloroethane, its metabolites, and other biomarkers of exposure and

effect to 1,1 -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 Associ ation

(APHA). Additionally, analytical methods are included that modify previously used methods to obtain

lower detection limits and/or to improve accuracy and precision.

The analytical methods used to quantify 1,1- dichlo roethane in biological and enviro nmental samples are

summarized below. Table 7 -1 lists the applicable analytical methods used for determining 1,1-dichloroethan e in biological fluids and tissues, and Table 7-2 lists the methods used for determining 1,1-dichloroethane in environmental samples.

7.1 BIOLOGICAL MATERIALS

T he determination of trace levels of 1,1

- dichloroethane in biological tissues and fluids has been restricted

to gas chromatography (GC) equipped with mass spectrometry (MS) or flame ionization detection (FID).

Work conducted by Cramer and co-workers (1988) showed that 1,1- dichloroethane can be detected at

nanogram per liter (ppt) levels in whole human blood using a dynamic headspace analyzer and GC/MS

technique. A disadvantage of the GC/MS technique is that only limite d mass scanning can be employed

to obtain better sensitivity of target VOCs at ppt levels. This is because of the inherent differences in

sensitivity between the full- scan MS and the limited mass scanning MS techniques (Cramer et al. 1988).

Uehori et al. (1987) developed a retention index in GC to screen and quantify VOCs in blood. A dynamic

headspace analyzer and GC/FID with retention indices were employed for the detection of 1,1-dichloroethane at nanogram levels. Uehori et al. (1987) noted that this method is simple and reliable, and requires

little or no sample preparation.

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### Table 7

- 1. Analytical Methods for Determining 1,1

- Dichloroethane in Biological

Materials

Sample matrix Preparation method Analytical

method Sample

det ection limit Percent

recovery Reference

Blood Vaporize blood sample in a headspace vial and inject into

GC column GC/FID ng range No data Uehori et al.

1987

Whole blood Purge

- and

- trap on Tenax

adsorbent GC/MS 100 ng/L 76

– 110 Cramer et

al. 1988

Blood an d urine Heat biological sample;

purge

- and

- trap volatile compounds on Tenax GC

adsorbent GC/MS No data No data Barkley et

al. 1980

Whole blood Collect by venipuncture, store cold; inject sample into purge

and

- trap apparatus GC/MS 0.013 ppb 102

– 118 Ashley e t al.

1992

Breath Collect human breath sample by means of a spirometer and analyze GC/MS Not detected No data Barkley et

al. 1980

Breath Collect human breath sample by means of a spirometer and analyze GC/MS Not reported No data Raymer et

al. 1990

FID = flame ionization detector; GC = gas chromatography; MS = mass spectrometry

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7. ANALYTICAL METHODS



### Table 7

- 2. Analytical Methods for Determining 1,1

- Dichloroethane in Environmental Samples

Sample Analytical Sample Percent

matrix Preparation method method de tection limit recovery Reference

Groundwater, Purge

- and

- trap (EPA GC/MS 5 μ g/L 59

– 155% EPA 1994a Method

aqueous method 624) or direct (groundwater; 8240 B sludges, injection (EPA Method 5 μ g/kg

caustic 5030) (soil/sediment) liquors, soils,

sediments

G roundwater, Purge

- and

- trap (EPA GC with 0.002 μ g/L 47

– 132 EPA 1994b Method surface water, method 624) or direct HECD 8010B

waste water injection (EPA Method 5030)

Groundwater Purge

- and

- trap on GC/MS 0.0001
– <±5 Lopez

- Avila et al.

absorbent 0.02 μg/sample relative 1987a

standard

deviation

Groundwater Purge

- and

- trap on GC/FID

- FID No data No data Driscoll et al. 1987

absorbent

Groundwater Purge

- and

- trap on GC/EICD

- FID Water=0.1
– 83

– 102 Lopez

- Avila 1987b

and soil absorbent 0.9 μg/L;

soil=1

– 5 μg/L

Drinking water Heat water sample; GC/MS Not detected No data Barkley et al. 1980

purge

- and

- trap volatile compounds on Tenax

GC absorbent

Drinking water Pass sample through GC/MS <1 μg/L No data Suffet et al. 1986

XAD

- 2 macroreticular

resin and extract continuously with ether

Drinking water Purge

- and

- trap water GC/MS 0.2 μg/L 94 Otson and Chan sample 1987

Drinking water Extract sample in GC

- EICD <1 μg/L No data Otson and Chan hexane and analyze

Drinking water Purge

- and

- trap on GC

- EICD

- FID <1 μg/ L >75 Otson and W illiams

Tenax absorbent 1982

Drinking water Purge

- and

- trap water GC/EICD 80 μg/L 84 Comba and Kaiser sample 1983

Drinking water Purge

- and

- trap water GC/EICD

- FID 0.1

– 0.5 μg/L No data Kingsley et al. 1983 sample

Water (river; Inject 1 mL into flow MIMS/ITD 0.2 ppb No data Bauer and Solyom sea) injection analysis 1994 system

Waste water Collect water sample GC/FID μg/L (ppb) <6 relative Blanchard and through a permeation range standard Hardy 1986

cell membrane and deviation

direct into GC

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### Table 7

- 2. Analytical Methods for Determining 1,1

- Dichloroethane in Environmental Samples

***DRAFT FOR PUBLIC COMMENT*** Sample Analytical Sample Percent

matrix Preparation method method de tection limit recovery Reference

Waste water Co llect sample through a permeation cell membrane; adsorb onto charcoal; extract with

carbon disulfide

Waste water Purge

- and

- trap (EPA (municipal method 601) w ith direct

and industrial aque o us injection; the discharges) t rap is backflushed and

heated to desorb compounds o nto column

Waste water Purge

- and

- trap (EPA (municipal method 624) ; the trap is

and industrial bac kflushed and heated discharges) t o desorb compounds

ont o column

Waste water Purge

- and

- trap w ith isotopic dilution (EPA method 1624); stable isotopes are added; the trap is backflushed and

heated to desorb compounds o nto column

Waste water Purge

- and

- trap on and sludge adsorbent

Drinking, Purge and trap water ground, and sample

surface water

Air (ambient) Purge

- and

- trap on

charcoal abs orbent;

extract with carbon

disulfide

Air (ambient) Collect air sample on Tenax adsorbent; vaporize thermally and analyze

Air (ambient) Collect air particulates on a glass fiber filter and Tenax GC adsorbent;

extract with MeOH pentane

Air (ambient) Adsorb air sample onto charcoal tube; extract

with carbon disulfide GC/FID 74
– 16,800 μg/L

GC/MS 0.07 μg/L

GC/MS 4.7 μ/L

GC/MS 10 μg/L

GC/MS No data

GC/AED 0.17 μg/L

GC/ECD 0.001 ppm

range

GC/MS 23 μg/m 3

GC/MS Not detected

GC/FID ppm range No data Blanchard and Hardy 1985

47

– 132 EPA 2001a

59

– 155 EPA 1999

Labeled EPA 2 001b compound

recovery: 23

– 1 91

No data Giabbaie et al. 1983

No data Silgoner et al. 1997

No data Bruner et al. 1978

No data Pellizari 1982

No data Barkley et al. 1980

No data NIOSH 2003 (method 1003)93 1,1

- DICHLOROETHANE

7. ANALYTICAL METHODS



### Table 7

- 2. Analytical Methods for Determining 1,1

- Dichloroethane in Environmental Samples

***DRAFT FOR PUBLIC COMMENT*** Sample Analytical Sample Percent

matrix Preparation method method de tection limit recovery Reference

Air (s pace Dehydrohalogenate air cabin) sample with lithium hydroxide and analyze

Air (high Collect vapor sample in humidity a Tedlar gas bag atmosphere)

Air Air collected in cooled trap; heated upon injection

Air (ambient) Collection on multiadsorbent traps;

automated preconcentration

Air Sample collected on

Tenax GC/carboxene 1000 trap, separated by capillary column

Various food Food containing >70% (e.g., dairy fat: dissolve sample in products, isooctane and shake ; meat, cleanup on florisil vegetables, column and soda)

Various food Cold liquid (4 °C) and (e.g., fruit aqueous flour

- based juices, soda, samples injected; coffees, plunge sampling tube or cream, peanut needle into dry/visc ous butter, and foods for injection; butter) steam distillation; purge and trap

Compound Prepare dilute solution

formulation of sample in MeOH;

introduce into headspace trap

Fish tissu e Add water to fish sample; homogenize

and extract ultrasonically; purge

and

- trap on adsorbent

Fish tissue Freeze fish sample; homogenize in liquid nitrogen; distill in

vacuum GC/MS 0.5

– 4.0 ppm

Portable 25 ppm organic vapor analyzer with

PID

GC/IMS No data

Capillary 0.71 ppbv

GC/MS

GC/PID/EICD 0.1 ppb

GC/ECD

- ng/g range

EICD

SD/PT/GC 0.003 μg/kg

GC/PID 20 pg

GC/MS 0.01 μg/g

GC/MS No data equipped with

fused

- silica capillar y column No data Spain et al. 1985

0.998 Barsky et al. 1985

correlation

coefficient

No data Simpson et al. 1996

Oliver et al. 199 6

Maeda et al. 1998

~70 Daft 1988

95.2 Page and Lacroix

1995

No data Jerpe and Davis

1987

77 Easley et al. 1981

No data Hiatt 198394 1,1

- DICHLOROETHANE

7. ANALYTICAL METHODS



### Table 7

- 2. Analytical Methods for Determining 1,1

- Dichloroethane in Environmental Samples

Sample Analytical Sample Percent

matrix Preparation method method de tection limit recovery Reference

Fish tissue Warm sample; purge

- GC/FID No data ~32 Reinert et al. 1983

and

- trap volatiles on

activated carbon adsorbent; extract with

carbon disulfide

Fish tissue Edible tissue and liver GC/EICD 5 pg/g 115±25 Roose and homogenized in blender; Brinkman 1998 organic

- free water and standard added; vial sealed and placed in ultrasonic bath; purge and trap

Whole fish Freeze fish sample and GC/MS 7.5x10 - 4 μg/g 6.2 relative Dreisch and homogenize; add MeOH equ ipped with standard Munson 1983

and extract fused

- silica deviation ultrasonically; purge

- capillary

and

- trap on adsorbent column

Fish and Add water containing GC/MS 0.025 μg/g Sediment Hiatt 1981

sediment acrolein and acrylonitrile matrix 1 01; to sample; freeze fish matrix sample; extract in 90

vacuum

AED = atomic emission detection; ECD = electron captive detector; EICD = electrolytic conductivity detector;

FID = flame ionization detector; GC = gas chromatography; HECD = Hall electrolytic conductivity detector; IMS = ion mobility spectrometry; ITD = ion trap detector; MIMS = membrane introduction mass spectrometry; MS = mass spectrometry; PID = photoionization detector; PT = purge

- and

- trap; SD = steam distillation

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Gas purging-and-trapping on a Tenax GC adsorbent and GC/MS technique has been employed by

Barkley et al. (1980) and Ashley et al. (1992) for the determination of trace levels of volatile halogenated

compounds (including 1,1-dichloroethane) in water, human blood, and urine.

7.2 ENVIRONMENTAL SAMPLES

A GC e quipped with an appropriate detector is the most frequently used analytical technique for

determining the concentrations of 1,1 -dichloroethane in air, water, soil, fish, dairy products, and various

foods. Volatile organic compounds in environmental sample s may exist as complex mixtures or at very

low concentrations (ppt to ppb range). Subsequently, the GC technique must be supplemented by some

method of sample preconcentration.

Gas purging-and-trapping is the generally accepted method for the isolation, concentration, and

determination of VOCs in water and various environmental samples (Bellar et al. 1979 ; EPA 1994,

1996b, 1999, 2001a, 2001b; Lopez-Avila et al. 1987a, 1987b; Page and Lacroix 1995; Reding 1987;

Wylie 1988). This method appears to be most adaptable for use with almost any GC detector

— MS, FID,

electron capture detector (ECD), and electrolytic conductivity detector (EICD). In addition, the method

offers an important preliminary separation of highly volatile compounds from often highly complex

samples prior to GC analysis. Det ection limits at <1 μg 1,1-dichloroethane/L of sample have been

achieved by this method (Dreisch and Munson 1983; Kingsley et al. 1983; Lopez- Avila et al. 1987a,

1987b; Otson and Williams 1982). Page and Lacroix (1995) successfully coupled purge-and-trap

procedures with steam distillation collection methods to yield an analytical method, for various foods,

with a detection limit of 0.003 μg/kg for 1,1-dichloroethane. Bruner et al. (1978) employed purge-andtrap technique on charcoal adsorbent and GC/ECD for determination at ppt levels of volatile halo organic

compounds in air. A major problem is that some of the halocarbons in the atmosphere are present as

ultra

- trace impurities in highly pure commercial inert gases. Subsequently, these impurities may interfere

with the quantitative and qualitative analysis of 1,1 -dichloroethane in environmental samples.

A purge-and-trap method with cryogenic trapping (cryofocusing) for concentrating VOCs from water

samples into the headspace

, for analysis by capillary G C, was described by Pankow and Rosen (1988).

The purge-and- trap technique offers advantages over other techniques in that it allows easy isolation and

concentration of target compounds, which reduces interference, thereby improving overall limits of

detec tion and recovery of sample (Otson and Chan 1987). Among the other advantages of the purge-andtrap technique with cryofocusing are its simplicity and therefore its reliability; the low background

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7. ANALYTICAL METHODS

contamination since no sorbent traps are needed; and the relatively short time of sample analysis (Pankow

and Rosen 1988). Roose and Brinkman (1998) capitalized on these techniques to analyze fish samples in

a rapid, selective, and sensitive manner. An automated GC system with dual multi

- adsorbent traps was

suc cessfully operated in a mobile laboratory to collect and analyze ambient air samples. The system

continuously collects air samples, uses a pre -concentration approach (cryofocusing), and recovers

analytes using thermal desorption. The detection limit for 1,1 -dichloroethane was reported as 0.71 ppbv

(Oliver et al. 1996).

Purge -and-trap techniques have been successfully coupled with atomic emission detection (AED) for the

analysis of water (Silgoner et al. 1997). Solutes eluting from the GC are atomized in a microwave

induced plasma, and individual wavelengths are measured using a photodiode array. The detection limit

of this method for 1,1-dichloroethane is 0.17 μg/L. While some improvement is still needed, the purgeand- trap technique coupled with AED offers some advantages over other methods. Dynamic headspace

analyzer GC has been used for the analysis and identification of 1,1 -dichloroethane in water and fish

tissue (Comba and Kaiser 1983; Mehran et al. 1986; Otson and Williams 1982; Reinert et al. 1 983;). The

analytic sample is placed in a sealed flask connected to the headspace analyzer, which is directly

interfaced with the injection port of the GC system. This arrangement allows for a greater proportion of

compound contained in a sample to be analyzed. Detection limits of <1 μg 1,1- dichloroethane/L water

and <1 μg 1,1-dichloroethane/g fish tissue were achieved (Mehran et al. 1986; Otson and Williams 1982;

Reinert et al. 1983; Trussel et al. 1983). A disadvantage of this technique is that the inherent vo latility of

the halo organic compounds gives rise to an excessive foaming in the headspace system, thereby forming

low yields and causing interference with the GC quantification. The typical yield of 1,1-dichloroethane

was approximately 32% (Reinart et al . 1983). The authors indicated that use of an antifoaming agent

such as silicone surfaces greatly reduced the foam, but extraneous chromatographic components and peak

masking problems were encountered.

Bauer and Solyom (1994) and Wong et al. (1995) reported that membrane introduction mass spectrometry

(MIMS) offers measurements of trace -level organics in environmental media, including polluted

seawater, without sample preparation, using a non-porous silicon membrane. A detection limit of 0.2 ppb

was repo rted for 1,1 -dichloroethane (Bauer and Solyom 1994).

Pellizzari (1982) initiated the development and evaluation of trace levels of VOCs in industrial and

chemical waste disposal sites. Ambient air samples were collected by a sampler equipped with Tenax G C

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7. ANALYTICAL METHODS

adsorbent cartridges. Compounds were thermally removed from the adsorbent and analyzed by capillary

GC/MS. The detection limit was at the μg/m 3 level (Pellizzari 1982).

Simpson et al. (1996) developed a method that has potential for on- site monitoring of vapor- phase

organics in air. GC is coupled with ion mobility spectrometry to offer high sensitivity and the ability to

operate at ambient pressure. While a detection limit for 1,1-dichloroethane was not reported, detection

limits for several other EP A priority pollutants ranged from 0.05 to 140 pg/second. Maeda et al. (1998)

also investigated analytical methods that may be applied to on-site monitoring techniques of HAPs. The

analytical methods that they employed included a Tenax GC and Carboxene 1000 trap, followed by

capillary separation and either photo ionization detector (PID) or EICD detection methods. The detection

limit of the system was reported as 0.1 ppb. Another method for sampling and analyzing VOCs in air is

proposed to have some adva ntages for use in field situations and may provide satisfactory results. The

method uses teraglyme as a sample enrichment tool and employs purge -and-trap methods along with

GC/MS (Huybrechts et al . 2001).

Blanchard and Hardy (1985, 1986) developed a method that allows for continuous monitoring or

intermittent analysis of volatile organic priority pollutants in environmental media. The method is based

on permeation of VOCs through a silicone polycarbonate membrane from wastewater sample matrix, into

an inert gas stream and directed into a capillary GC/FID via a sampling loop (Blanchard and Hardy 1986).

Advantages of this procedure are that it is simple, it does not require time -consuming preconcentration

steps, and it can be used either in the field or in the laboratory.

The liquid-liquid extraction procedure provides a simple, rapid, screening method for semiquantitative

determination of 1,1-dichloroethane in aqueous samples containing limited number of VOCs. It is less

effective for aqueous samples containing large numbers of VOCs. Furthermore, interference from the

organic (hexane) extraction solvent makes it more difficult to identify completely all compounds (Otson

and Williams 1981). GC/EICD was employed by Otson and Williams (1981) for the de tection of trace

amounts (<1 μg/L of sample) of 1,1-dichloroethane in drinking water.

Daft (1988) employed a photoionization detector and an electrolytic conductivity detector connected in

series to a capillary GC to detect 1,1

- dichloroethane at ng/g leve ls in fumigants and industrial chemical

residues of various foods (e.g., dairy products, meat, vegetables, and soda). Typically, foods were

extracted with isooctane and injected in GC column for analysis. However, foods containing lipid and fat

were subjected to further clean -up on micro-florisil column prior to GC analysis.

***DRAFT FOR PUBLIC COMMENT***98 1,1

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7. ANALYTICAL METHODS

A procedure was developed by Hiatt (1983) and Dreisch and Munson (1983) to identify and quantify

1,1- dichloroethane in fish tissue samples by GC/MS, employing a fused

- silica capillar y column (FSCC)

and vacuum distillation (extraction). An advantage of the vacuum extraction is that the system does not

require elevated temperatures or the addition of reagents, which could produce unwanted degradation

products (Hiatt 1981). The FSCC pr ovides a more attractive approach than packed column for

chromatographic analysis of VOCs, because FSCC can be heated to a higher -temperature (350 °C) than

that recommended for packed column thereby improving the resolution (at the ng/g level) of compounds

at a lesser retention time. A physical limitation for compounds that can be detected, however, is that the

vapor pressure of the compounds must be >0.78 torr (approximately 50 °C) in the sample chamber (Hiatt

1983).

7.3 ADEQUACY OF THE DATABASE

S ect ion 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with the

Administrator of EPA and agencies and programs of the Public Health Service) to assess whether

adequate information on the health effects of 1,1-dichloroethan e is available. Where adequate

information is not available, ATSDR, in conjunction with NTP, is required to assure the initiation of a

program of research designed to determine the health effects (and techniques for developing methods to

determine such he alth effects) of 1,1 -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 re search agenda will be proposed.

7.3.1 Identification of Data Needs

M ethods for Determining Biomarkers of Exposure and Effect. Reliable methods are available

for detecting and quantifying 1,1-dichloroethane in the tissues and body fluids of humans. GC/MS or

GC/FID has been employed to detect 1,1-dichloroethane at nanogram to picogram levels in blood and

tissue samples of humans. No additional analytical methods for determining trace levels of 1,1 -dichloroethane in the blood of humans are needed. Also, no detection limits for detecting 1,1- dichloroethane in

urine samples by GC/MS were indicated by Barkley et al. (1980). Therefore, additional research and

***DRAFT FOR PUBLIC COMMENT***99 1,1

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7. ANALYTICAL METHODS

development of sensitive and selective methods for detecting and quantifying the levels of

1,1-dichloroethane and its metabolites in the tissues and urine of humans would be useful. If methods

were available, it would assist investigators in determining whether specific levels of 1,1 -dichloroethane

found in the tissues/fluids of exposed persons c orrelate with any adverse health effects.

Methods for Determining Parent Compounds and Degradation Products in Environmental

Media. Analytical methods are available to detect 1,1

- dichloroethane in environmental samples.

Purge -and- trap or direct inject ion followed by analysis with GC/ECD and GC/MS have been used to

detect and quantify 1,1-dichloroethane in water samples at ppt and ppb levels (methods 5030, 8240,

8010B [EPA 1994a, 1994b, 1996b]; method 601, 624, 1624 [EPA 1999, 2001a, 2001b]). GC equipp ed

with FID, PID, or EICD has also been used to detect and quantify 1,1-dichloroethane in air, water, milk,

vegetables, and fish at ppb levels NIOSH (method 1003 [NIOSH 2003 ]). No additional analytical

methods for determining trace levels of 1,1

- dichloroe thane in environmental media are needed.

7.3.2 Ongoing Studies

No ongoing studies regarding sponsored by NIH or EPA were identified for 1,1-dichloroethane.

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7. ANALYTICAL METHODS



### This page is intentionally blank.

***DRAFT FOR PUBLIC COMMENT***101 1,1

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### 8. REGULATIONS, ADVISORIES, AND GUIDELINES

MRLs are substance specific estimates, which are intended to serve as screening levels, are used by

ATSDR health assessors and other responders to identify contaminants and potential health effects that

may be of concern at hazardous waste sites.

No inhalation or ora l MRLs were derived for 1,1 -dichloroethane.

The EPA (IRIS 2012) has not derived an oral reference dose (RfD) or an inhalation reference

concentration (RfC) for 1,1 -dichloroethane.

1,1- Dichloroethane appears on the list of chemicals in “The Emergency Plan ning and Community Rightto -Know Act of 1986” and has been assigned a reportable quantity (RQ) limit of 1,000 pounds (EPA

2011g). The RQ represents the amount of a designated hazardous substance which, when released to any

environmental media, must be reported to the appropriate authority. 1,1-Dichloroethane also appears on

the EPA’s list as a priority candidate for the drinking water contaminant list (EPA 1998a).

The international and national regulations, advisories, and guidelines regarding 1,1-dichlo roethane in air,

water, and other media are summarized in Table 8

- 1

.

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8. REGULATIONS, ADVISORIES, AND GUIDELINES



### Table 8

- 1. Regulations, Advisories, and Guidelines Applicable to 1,1

- Dichloroethane

Agency Description Information Reference

INTERNATIONAL

Guidelines:

IARC Carcinogenicity classification No data IARC 2012

WHO Air quality guidelines

Drinking water quality guidelines No data

No data a WHO 2010

WHO 2008

NATIONAL

Regulations and

Guidelines:

a. Air

ACGIH TLV (8

- hour TWA) 100 ppm ACGIH 2011

AIHA ERPGs No data A IHA 2011

DOE PAC

- 1 and PAC

- 2 b

PAC

- 3 b 160 ppm

4,000 ppm DOE 2012

EPA AEGLs No data EPA 2011a

Second AEGL chemical priority list Yes EPA 2012a

Hazardous air pollutant Yes EPA 2012b

42 USC 7412

NIOSH NAAQS

REL (10

- hour TWA) No data

10 0 ppm c EPA 2010b

NIOSH 201 1

IDLH 3,000 ppm

OSHA PEL (8

- hour TWA) for general industry 100 ppm OSHA 2012 29 CFR 1910.1000,

Table Z

- 1

b. W ater

EPA Designated as hazardous substances in

accordance with Section 311(b)(2)(A) of

the Clean Water Act No data EPA 2011b

40 CFR 116.4

Drinking water contaminant candidate

list Yes EPA 1998a

63 FR 10274

Drinking water standards and health

advisories No data EPA 2011c

Master Testing List Yes d EPA 2012c

National primary drinking water

standards No data EPA 2009a

National recommended water quality

criteria: human health for the consumption of No data EPA 2009b

Reportable quantities of hazardous substances designated pursuant to

Section 311 of the Clean Water Act No data EPA 2011f

40 CFR 117.3

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8. REGULATIONS, ADVISORIES, AND GUIDELINES



### Table 8

- 1. Regulations, Advisories, and Guidelines Applicable to 1,1

- Dichloroethane

Agency Description Information Reference

NATIONAL (cont.)

c. Food

FDA EAFUS e No data FDA 2012

d. Other

ACGIH Carcinogenicity classification A4 f ACGIH 2011

EPA Carcinogenicity classification C g IRIS 2012

RfC No data

RfD No data

Identification and listing of hazardous

waster U076 EPA 2011d

4 0 CFR 261, Appendix VIII

Inert pesticide ingredients in pesticide products No data EPA 2011e

RCRA waste minimization PBT priority

chemical list Yes EPA 1998b

63 FR 60332

Standards for owners and operators of hazardous waste TSD facilities; groundwat er monitoring list Yes EPA 2011j 40 CFR 264, Appendix IX

Superfund, emergency planning, and community right

- to

- know

Designated CERCLA hazardous substance and reportable quantity 1,000 pounds h EPA 2011g

40 CFR 302.4

Effective date of toxic chemica l release reporting 01/01/1994 EPA 2011h

40 CFR 372.65

Extremely hazardous substances and its threshold planning quantity No data EPA 2011i 40 CFR 355, Appendix A

TSCA chemical lists and reporting periods EPA 2011k

40 CFR 712.30

Effective date 03/ 11/1994

Reporting date 05/10/1994

TSCA health and safety data reporting

Effective date 06/01/1987 EPA 2011l

40 CFR 716.120

Reporting date 06/01/1997

NTP Carcinogenicity classification No data NTP 2011

a In view of the very limited databa se on toxicity and carcinogenicity, the Guidelines concluded that no guideline value for 1,1

- dichloroethane should be proposed.

b PAC- 1: mild, transient health effects. PAC- 2: irreversible or other serious health effects that could impair the ability

to ta ke protective action. PAC- 3: life

- threatening health effects.

c NIOSH recommends that 1,1

- dichloroethane be treated in the workplace with caution because of their structural similarity to the four chloroethanes (ethylene dichloride, hexachloroethane, 1,1,2 ,2

- tetrachloroethane, and 1,1,2

- trichloroethane) shown to be carcinogenic in animals.

d 1,

- Dichloroethane was recommended to the MTL by the EPA’s Office of Water and Office of Drinking Water in 1990

and was later removed in 1995. The initial chemical testi ng program was for prechronic toxicity (14

– 28 day) and subchronic toxicity (90 day) health effects.

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8. REGULATIONS, ADVISORIES, AND GUIDELINES



### Table 8

- 1. Regulations, Advisories, and Guidelines Applicable to 1,1

- Dichloroethane

Agency Description Information Reference

e The EAFUS list of substances contains ingredients added directly to food that FDA has either approved as food

additives or listed or affirmed as GRAS.

f A4: not classifiable as a human carcinogen

g C: possible human carcinogen

h Designated CERCLA hazardous substance pursuant to Section 307(a)of the Clean Water Act, Section 112 of the Clean Air Act, and Section 3001 of RCRA.

ACGIH = American Conference of Governmental Industrial Hygienists; AEGL = acute exposure guideline levels;

AIHA = American Industrial Hygiene Association; CERCLA = Comprehensive Environmental Response, Compensation, and Liability Act; CFR = Code of Federal Regulations; DOE = Department of En ergy; EAFUS = Everything Added to Food in the United States; EPA = Environmental Protection Agency;

ERPG = emergency response planning guidelines; FDA = Food and Drug Administration; FR = Federal Register;

GRAS = Generally Recognized As Safe; IARC = Intern ational Agency for Research on Cancer; IDLH = immediately dangerous to life or health; IRIS = Integrated Risk Information System; MTL = Master Testing List; NAAQS = National Ambient Air Quality Standards; NIOSH = National Institute for Occupational Safety and Health; NTP = National Toxicology Program; OSHA = Occupational Safety and Health Administration; PAC = Protective Action Criteria;

PBT = Persistent, Bioaccumulative, and Toxic; PEL = permissible exposure limit; RCRA = Resource Conservation and Recovery Act; REL = recommended exposure limit; RfC = inhalation reference concentration; RfD = oral reference dose; TLV = threshold limit values; TSCA = Toxic Substances Control Act; TSD = treatment, storage, and disposal; TWA = time

- weighted average; USC = Unite d States Code; WHO = World Health Organization

***DRAFT FOR PUBLIC COMMENT***_______________________ 105 1,1

- DICHLOROETHANE



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### 10. GLOSSARY

Absorption

— The taking up of liquids by solids, or of gases by solids or liquids.

Acute Exposure

— Exposure to a chemical for a duration of 14 days or less, as specified in the Toxicological Profiles.

Adsorption

— The adhesion in an extremely thin layer of molecules (as of gases, solutes, or liquids) to the surfaces of solid bodies or liquids with which they are in contact.

Adsorption Coefficient (K

oc )— The ratio of the amount of a chemical adsorbed per unit weight of organic carbon in the soil or sediment to the concentration of the chemical in solution at equilibrium.

Adsorption Ratio (Kd)

— The amount of a chemical adsorbed by sediment or soil (i.e., the solid phase) divided by the amount of chemical in the solution phase, which is in equilibrium with the solid phase, at a

fixed solid/solution ratio. It is generally expressed in micrograms of chemical sorbed per gram of soil or

sediment.

Benchmark Dose (BMD)

— Usually defined as the lower confidence limit on the dose that produces a specified magnitude of changes in a specified adverse response. For example, a BMD 10 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 chemica l 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 inci dence of cancer (or tumors) between the exposed population and its appropriate control.

Carcinogen

— A chemical capable of inducing cancer.

Case

- Control Study

— A type of epidemiological study that examines the relationship between a particular outcome (disease or condition) and a variety of potential causative agents (such as toxic chemicals). In a case -controlled study, a group of people with a specified and well-defined outcome is identified and compared to a similar group of people without outcome.

Case Report

— Describes a single individual with a particular disease or exposure. These may suggest some potential topics for scientific research, but are not actual research studies.

Case Series

— Describes the experience of a small number of individuals with the same disease or exposure. These may suggest potential topics for scientific research, but are not actual research studies.

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10. GLOSSARY

Ceiling Value

— A concentration of a substance that should not be exceeded, even instantaneously.

Chronic Exposure

— Exposure to a chemical for 365 days or more, as specified in the Toxicological

Profiles.

Cohort Study

— A type of epidemiological study of a specific group or groups of people who have had a common insult (e.g., exposure to an agent suspected of causing disease or a common disease) and are followed forward from exposure to outcome. At least one exposed group is compared to one unexposed

group.

Cross

- sectional Study

— A type of epidemiological study of a group or groups of people that examines the relationship between exp osure 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 ex posure 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 sp ecific 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 w ithin 30 minutes without any escape-impairing symptoms or

irreversible health effects.

Immunologic Toxicity— The occurrence of adverse effects on the immune system that may result from exposure to environmental agents such as chemicals.

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10. GLOSSARY

Immunological Effe cts

— Functional changes in the immune response.

Incidence

— The ratio of individuals in a population who develop a specified condition to the total number of individuals in that population who could have developed that condition in a specified time period.

Intermediate Exposure

— Exposure to a chemical for a duration of 15– 364 days, as specified in the Toxicological Profiles.

In Vitro

— Isolated from the living organism and artificially maintained, as in a test tube.

In Vivo

— Occurring within the living organi sm.

Lethal Concentration (LO) (LC LO )— The lowest concentration of a chemical in air that has been reported

to have caused death in humans or animals.

Lethal Concentration (50) (LC 50 )— A calculated concentration of a chemical in air to which exposure for

a sp ecific length of time is expected to cause death in 50% of a defined experimental animal population.

Lethal Dose (LO) (LD Lo )— 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) (LD 50 )— The dose of a chemical that has been calculated to cause death in 50% of a defined experimental animal population.

Lethal Time (50) (LT 50 )— A calculated period of time within which a specific concentration of a chemical

is e xpected 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 increase s 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— Perma nent structural changes that may adversely affect survival, development, or

function.

Minimal Risk Level (MRL)

— An estimate of daily human exposure to a hazardous substance that is likely to be without an appreciable risk of adverse noncancer health effects over a specified route and duration of exposure.

Modifying Factor (MF)

— A value (greater than zero) that is applied to the derivation of a Minimal Risk Level (MRL) to reflect additional concerns about the database that are not covered by the uncertainty

factors. The default value for a MF is 1.

Morbidity

— State of being diseased; morbidity rate is the incidence or prevalence of disease in a specific population.

Mortality— Death; mortality rate is a measure of the number of deaths in a population during a specified

interval of time.

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10. GLOSSARY

Mutagen

— A substance that causes mutations. A mutation is a change in the DNA sequence of a cell’s DNA. Mutations can lead to birth defects, miscarriages, or cancer.

Necropsy

— The gross examination of the organs and tissues of a dead body to determine the cause of death or pathological conditions.

Neurotoxicity— The occurrence of adverse effects on the nervous system following exposure to a

chemical.

No

- Observed

- Adverse

- Effect Level (NOAEL)

— The dose of a chemical at which the re 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 (K

ow )— The equilibrium ratio of the concentrations of a chemical

in n -octanol and water, in dilute solution.

Odds Ratio (OR)

— A means of measuring the association between an exposure (such as toxic substances and a disease or condition) that represents the best estimate of relative risk (risk as a ratio of the incidence among subjects exposed to a particular risk factor divided by the incidence among subjects who were not exposed to the risk factor). An OR of greater than 1 is considered to indicate greater risk of disease in the exposed group compared to the unexposed group.

Organophosphate or Organophosphorus Compound

— A phosphorus-containing organic compound and especially a pesticide that acts by inhibiting cholinesterase.

Permissible Exposure Limit (PEL)

— An Occupational Safety and Health Administration (OSHA) allowable exposure level in workplace air averaged over an 8 -hour shift of a 40-hour workweek.

Pesticide

— General classification of chemicals specifically develop ed and produced for use in the control of agricultural and public health pests.

Pharmacokinetics

— The dynamic behavior of a material in the body, used to predict the fate (disposition) of an exogenous substance in an organism. Utilizing computational tech niques, it provides the means of studying the absorption, distribution, metabolism, and excretion of chemicals by the body.

Pharmacokinetic Model

— A set of equations that can be used to describe the time course of a parent chemical or metabolite in an animal system. There are two types of pharmacokinetic models: data

- based and physiologically-based. A data- based model divides the animal system into a series of compartments, which, in general, do not represent real, identifiable anatomic regions of the body, whereas the physiologically-based model compartments represent real anatomic regions of the body.

Physiologically Based Pharmacodynamic (PBPD) Model

—A type of physiologically based doseresponse model that quantitatively describes the relationship bet ween 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.

Physiol ogically 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

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10. GLOSSARY

variety of physiological information: tissue volumes, blood flow rates t o 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 bas ed 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 s tudy. A group is followed over time.

q 1 *— The upper-bound estimate of the low-dose slope of the dose-response curve as determined by the multistage procedure. The q 1 * can be used to calculate an estimate of carcinogenic potency, the

incremental excess ca ncer risk per unit of exposure (usually μg/L for water, mg/kg/day for food, and μg/m 3 for air).

Recommended Exposure Limit (REL)

— A National Institute for Occupational Safety and Health (NIOSH) time

- weighted average (TWA) concentration for up to a 10 -hour workday during a 40-hour

workweek.

Reference Concentration (RfC)

— An estimate (with uncertainty spanning perhaps an order of magnitude) of a continuous inhalation exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious noncancer health effects during a lifetime. The inhalation reference concentration is for continuous inhalation exposures and is appropriately expressed in units of mg/m 3 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

- adver se

- 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 d atabase 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 Li ability 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.

Re productive Toxicity

— The occurrence of adverse effects on the reproductive system that may result from exposure to a chemical. The toxicity may be directed to the reproductive organs and/or the related endocrine system. The manifestation of such toxicity may be noted as alterations in sexual behavior, fertility, pregnancy outcomes, or modifications in other functions that are dependent on the integrity of this system.

Retrospective Study

— A type of cohort study based on a group of persons known to have been exposed at some time in the past. Data are collected from routinely recorded events, up to the time the study is undertaken. Retrospective studies are limited to causal factors that can be ascertained from existing records and/or examining survivors of the cohort.

Risk

— The possibility or chance that some adverse effect will result from a given exposure to a chemical.

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10. GLOSSARY

Risk Factor

— An aspect of personal behavior or lifestyle, an environmental exposure, or an inborn or

inherited characteristic that is ass ociated 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 ind icates greater risk of disease in the exposed group compared to the unexposed group.

Short

- Term Exposure Limit (STEL)

— The American Conference of Governmental Industrial Hygienists (ACGIH) maximum concentration to which workers can be exposed for up to 15 minutes continually. No more than four excursions are allowed per day, and there must be at least 60 minutes between exposure periods. The daily Threshold Limit Value- Time Weighted Average (TLV

- TWA) may

not be exceeded.

Standardized Mortality Ratio (SMR)— A ratio of the observed number of deaths and the expected number of deaths in a specific standard population.

Target Organ Toxicity

— This term covers a broad range of adverse effects on target organs or physiological systems (e.g., renal, cardiovascular) extending from those arising through a single limited exposure to those assumed over a lifetime of exposure to a chemical.

Teratogen

— A chemical that causes structural defects that affect the development of an organism.

Threshold Limit Value (TLV)

— An Ame rican 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 a s 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) (TD 50 )— A calculated dose of a chemical, introduced by a route other than inhalation,

which i s expected to cause a specific toxic effect in 50% of a defined experimental animal population.

Toxicokinetic

— The absorption, distribution, and elimination of toxic compounds in the living organism.

Uncertainty Factor (UF)

— A factor used in operationally deriving the Minimal Risk Level (MRL) or Reference Dose (RfD) or Reference Concentration (RfC) from experimental data. UFs are intended to account for (1) the variation in sensitivity among the members of the human population, (2) the uncertainty in extra polating animal data to the case of human, (3) the uncertainty in extrapolating fromdata obtained in a study that is of less than lifetime exposure, and (4) the uncertainty in using lowestobserved

- adverse

- effect level (LOAEL) data rather than no

- observed

- adverse

- effect level (NOAEL) data. A default for each individual UF is 10; if complete certainty in data exists, a value of 1 can be used; however, a reduced UF of 3 may be used on a case -by- case basis, 3 being the approximate logarithmic average of 10 a nd 1.

Xenobiotic

— Any chemical that is foreign to the biological system.

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### APPENDIX A. ATSDR MINIMAL RISK LEVELS AND WORKSHEETS

The Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) [42 U.S.C.

9601 et seq.], as amended by the Superfund Amendments and Reauthorization Act (SARA) [Pub. L. 99–

499], requires that the Agency for Toxic Substances and Disease Registry (ATSDR) develop jointly with

the U.S. Environmental Protection Agency (EPA), in order of priority, a list of hazardous substances most

commonly found at facilities on the CERCLA National Priorities List (NPL); prepare toxicological

profiles for each substance included on the priority list of hazardous substances; and assure the i nitiation

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

gi ven 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 t o 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 occ ur.

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

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APPENDIX A

are not expected to cause adverse health effects. Most MRLs contain a degree of uncertainty because of

the lack of precise toxicological information on the people who might be most sensitive (e.g., infants,

elderly, nutritionally or immunologically compromised) to the effects of hazardous substanc es. ATSDR

uses a conservative (i.e., protective) approach to address this uncertainty consistent with the public health

principle of prevention. Although human data are preferred, MRLs often must be based on animal studies

because relevant human studies are lacking. In the absence of evidence to the contrary, ATSDR assumes

that humans are more sensitive to the effects of hazardous substance than animals and that certain persons

may be particularly sensitive. Thus, the resulting MRL may be as much as 100

- fold below levels that

have been shown to be nontoxic in laboratory animals.

Proposed MRLs undergo a rigorous review process: Health Effects/MRL Workgroup reviews within the

Division of Toxicology and Human Health Sciences , expert panel peer reviews, and agency

- wide MRL

Workgroup reviews, with participation from other federal agencies and comments from the public. They

are subject to change as new information becomes available concomitant with updating the toxicological

profiles. Thus, MRLs in the most recent toxicological profiles supersede previously published levels.

For additional information regarding MRLs, please contact the Division of Toxicology and Human

Health Sciences , Agency for Toxic Substances and Disease Registry, 1600 Clifton Road NE, M ailstop

F-57, Atlanta, Georgia 30333.

MRLs were not derived for 1,1-dichloroethane, as discussed in Section 2.3.

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### APPENDIX B. USER'S GUIDE

Chapter 1

Public Health Statement

T his 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 t he 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 ev aluations of existing toxicologic,epidemiologic, and toxicokinetic information. This summary is designed to present interpretive, weightof-evidence discussions for human health end points by addressing the following questions:

1. What effects are know n 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 orde r that they appear within the Discussion of Health Effects by Route of Exposure section, by route (inhalation, oral, and dermal) and within route by effect. Human data are presented first, then animal data. Both are organized by duration (acute, intermed iate, chronic).

In vitro data and data from parenteral routes (intramuscular, intravenous, subcutaneous, etc.) are also considered in this chapter.

The carcinogenic potential of the profiled substance is qualitatively evaluated, when appropriate, using existing toxicokinetic, genotoxic, and carcinogenic data. ATSDR does not currently assess cancer potency or perform cancer risk assessments. Minimal Risk Levels (MRLs) for noncancer end points (if derived) and the end points from which they were derived are indicated and discussed.

Limitations to existing scientific literature that prevent a satisfactory evaluation of the relevance to public health are identified in the Chapter 3 Data Needs section.

Interpretation of Minimal Risk Levels

Where sufficie nt toxicologic information is available, ATSDR has derived MRLs for inhalation and oral routes of entry at each duration of exposure (acute, intermediate, and chronic). These MRLs are not meant to support regulatory action, but to acquaint health professi onals with exposure levels at which adverse health effects are not expected to occur in humans.

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APPENDIX B

MRLs should help physicians and public health officials determine the safety of a community living near a chemical emission, given the concentration of a conta minant 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. Cha pter 2, "Relevance to Public Health," contains basic information known about the substance. Other sections such as Chapter 3 Section 3.9, "Interactions with Other Substances,” and Section 3.10, "Populations that are Unusually Susceptible" provide important supplemental information.

MRL users should also understand the MRL derivation methodology. MRLs are derived using a modified version of the risk assessment methodology that the Environmental Protection Agency (EPA) provides (Barnes and Dourson 1988) to determine reference doses (RfDs) for lifetime exposure.

To derive an MRL, ATSDR generally selects the most sensitive end point which, in its best judgement, represents the most sensitive human health effect for a given exposure route and duration. ATS DR 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 ar e available, ATSDR derives an MRL using the most sensitive species (when information from multiple species is available) with the highest no

- observed

- adverse

- effect level (NOAEL) that does not exceed any adverse effect levels. When a NOAEL is not available, a

lowest

- observed

- adverse

- effect level (LOAEL) can be used to derive an MRL, and an uncertainty factor (UF) of 10 must be employed. Additional uncertainty factors of 10 must be used both for human variability to protect sensitive subpopulations (people who are most susceptible to the health effects caused by the substance) and for interspecies variability (extrapolation from animals to humans). In deriving an MRL, these individual uncertainty factors are multiplied together. The product is then

divide d into the inhalation concentration or oral dosage selected from the study. Uncertainty factors used in developing a substance- specific MRL are provided in the footnotes of the levels of significant exposure (LSE) tables.

Chapter 3

Health Effects

Ta ble s and Figures for Levels of Significant Exposure (LSE)

Tables and figures are used to summarize health effects and illustrate graphically levels of exposure associated with those effects. These levels cover health effects observed at increasing dose

conc entrations and durations, differences in response by species, MRLs to humans for noncancer end points, and EPA's estimated range associated with an upper- bound individual lifetime cancer risk of 1 in 10,000 to 1 in 10,000,000. Use the LSE tables and figu res 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 reliab le, quantitative estimates of NOAELs, LOAELs, or Cancer Effect Levels (CELs).

The legends presented below demonstrate the application of these tables and figures. Representative examples of LSE Table 3 -1 and Figure 3-1 are shown. The numbers in the left column of the legends correspond to the numbers in the example table and figure.

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APPENDIX B

LEGEND See Sample LSE Table 3

- 1 (page B -6)

(1) Route of Exposure . One of the first considerations when reviewing the toxicity of a substance using these tables and figure s should be the relevant and appropriate route of exposure. Typically when sufficient data exist, three LSE tables and two LSE figures are presented in the document. The three LSE tables present data on the three principal routes of exposure, i.e., inhalation, oral, and dermal (LSE Tables 3 -1, 3-2, and 3- 3, respectively). LSE figures are limited to the inhalation (LSE Figure 3 -1) and oral (LSE Figure 3- 2) routes. Not all substances will have data on each route of exposure and will not, therefore, have a ll 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 defi ned in the "System" column of the LSE table (see key number 18).

(4) Key to Figure . Each key number in the LSE table links study information to one or more data points using the same key number in the corresponding LSE figure. In this example, the study represented by key number 18 has been used to derive a NOAEL and a Less Serious LOAEL (also see the two "18r" data points in sample Figure 3-1).

(5) Species . The test species, whether animal or human, are identified in this column. Chapter 2, "Relevance to Public Health," covers the relevance of animal data to human toxicity and

Section 3.4, "Toxicokinetics," contains any available information on comparative toxicokinetics. Although NOAELs and LOAELs are species specific, the levels are extrapolated to equivalent

human doses to derive an MRL.

(6) Exposure Frequency/Duration . The duration of the study and the weekly and daily exposure regimens are provided in this column. This permits comparison of NOAELs and LOAELs from

different studies. In this ca se (key number 18), rats were exposed to “Chemical x” via inhalation for 6 hours/day, 5 days/week, for 13 weeks. For a more complete review of the dosing regimen, refer to the appropriate sections of the text or the original reference paper (i.e., Nitschke et al. 1981).

(7) System . This column further defines the systemic effects. These systems include respiratory, cardiovascular, gastrointestinal, hematological, musculoskeletal, hepatic, renal, and dermal/ocular. "Other" refers to any systemic effect (e.g., a decrease in body weight) not covered in these systems. In the example of key number 18, one systemic effect (respiratory) was investigated.

(8) NOAEL . A NOAEL is the highest exposure level at which no harmful effects were seen in the

organ syst em 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").

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APPENDIX B

(9) LOAEL . A LOAEL is the lowest dose used in the study that caused a harmful health effect. LOAELs have been classified into "Less Serious" and "Serious" effects. These distinctions help readers identify the levels of exposure at which adverse health effects first appear and the gradation of effects with increasing dose. A br ief 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) Referen ce . The complete reference citation is given in Chapter 9 of the profile.

(11) CEL . A CEL is the lowest exposure level associated with the onset of carcinogenesis in experimental or epidemiologic studies. CELs are always considered serious effects. Th e 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. Foo tnote "b" indicates that the NOAEL of 3 ppm in key number 18 was used to

derive an MRL of 0.005 ppm.

LEGEND

Se e Sample Figure 3

- 1 (page B

- 7)

L SE figures graphically illustrate the data presented in the corresponding LSE tables. Figures help the

reader quickly compare health effects according to exposure concentrations for particular exposure periods.

(13) Exposure Period . The same exposure periods appear as in the LSE table. In this example, health

effects observed within the acute and intermediate e xposure 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 hea lth 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/m 3 or ppm and oral exposure is reported in mg/kg/day.

(16) NOAEL . In this example, the open circle designated 18r identifies a NOAEL critical end point in the rat upon which an intermediate inhalation exposure MRL is based. The key number 18 corresponds to the entry in the LSE table. The dashed descending arrow indicates the extrapolation from the exposure level of 3 ppm (see entry 18 in the table) to the MRL of

0.005 ppm (see footnote "b" in the LSE table).

(17) CEL . Key number 38m is one of three studies for which CELs were derived. The diamond symbol refers to a CEL for the test species -mouse. The number 38 corresponds to the entry in the

LSE table.

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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. Thes e 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 (q 1 *).

(19) Key to LSE Figure . The Key explains the abbreviations and symbols used in the figure.

***DRAFT FOR PUBLIC COMMENT***1234→SAMPLETable 3-1. Levels of Significant Exposure to [Chemical x]–Inhalation→→Exposurefrequency/durationSpeciesKey tofigureaINTERMEDIATE EXPOSURE↓6↓5SystemicSystem↓7NOAEL(ppm)↓8LOAEL (effect)Less serious(ppm)↓9Serious (ppm)Reference↓10→→Nitschke et al. 1981CHRONIC EXPOSUREWong et al. 1982NTP 1982NTP 1982(CEL, multipleorgans)(CEL, lung tumors,nasal tumors)(CEL, lung tumors,hemangiosarcomas)10 (hyperplasia)11↓2010103bResp13 wk5 d/wk6 hr/d18 mo5 d/wk7 hr/d89–104 wk5 d/wk6 hr/d79–103 wk5 d/wk6 hr/dRatRatRatMouse18Cancer383940aThe number corresponds to entries in Figure 3-1.bUsed to derive an intermediate inhalation Minimal Risk Level (MRL) of 5x10-3ppm; dose adjusted for intermittent exposure and dividedby an uncertainty factor of 100 (10 for extrapolation from animal to humans, 10 for human variability).12 B-6 1,1

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APPENDIX B

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### APPENDIX C. ACRONYMS, ABBREVIATIONS, AND SYMBOLS

ACGIH American Conference of Governmental Industrial Hygienists

ACOEM American College of Occupational and Environmental Medicine

ADI acceptable daily i ntake

ADME absorption, distribution, metabolism, and excretion

AED atomic emission detection

AFID alkali flame ionization detector

AFOSH Air Force Office of Safety and Health

ALT alanine aminotransferase

AML acute myeloid leukemia

AOAC Association of Offic ial Analytical Chemists

AOEC Association of Occupational and Environmental Clinics

AP alkaline phosphatase

APHA American Public Health Association

AST aspartate aminotransferase

atm atmosphere

ATSDR Agency for Toxic Substances and Disease Registry AWQC Amb ient Water Quality Criteria

BAT best available technology

BCF bioconcentration factor

BEI Biological Exposure Index

BMD/C benchmark dose or benchmark concentration

BMD X dose that produces a X% change in response rate of an adverse effect

BMDL X 95% lower co nfidence limit on the BMD X BMDS Benchmark Dose Software

BMR benchmark response

BSC Board of Scientific Counselors

C centigrade

CAA Clean Air Act

CAG Cancer Assessment Group of the U.S. Environmental Protection Agency

CAS Chemical Abstract Services

CDC Ce nters for Disease Control and Prevention

CEL cancer effect level

CELDS Computer- Environmental Legislative Data System

CERCLA Comprehensive Environmental Response, Compensation, and Liability Act

CFR Code of Federal Regulations

Ci curie

CI confidence interv al

CL ceiling limit value

CLP Contract Laboratory Program

cm centimeter

CML chronic myeloid leukemia

CPSC Consumer Products Safety Commission

CWA Clean Water Act

DHEW Department of Health, Education, and Welfare

DHHS Department of Health and Human Services

DNA deoxyribonucleic acid

DOD Department of Defense

DOE Department of Energy

DOL Department of Labor

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APPENDIX C

DOT Department of Transportation

DOT/UN/ Department of Transportation/United Nations/

NA/IMDG North America/Intergovernmental Maritime Dangerous G oods Code

DWEL drinking water exposure level

ECD electron capture detection

ECG/EKG electrocardiogram

EEG electroencephalogram

EEGL Emergency Exposure Guidance Level

EPA Environmental Protection Agency

F Fahrenheit

F 1 first

- filial generation

FAO Food and Agricultural Organization of the United Nations

FDA Food and Drug Administration

FEMA Federal Emergency Management Agency

FIFRA Federal Insecticide, Fungicide, and Rodenticide Act

FPD flame photometric detection fpm feet per minute

FR Federal Register

FSH f ollicle stimulating hormone

g gram GC gas chromatography gd gestational day

GLC gas liquid chromatography

GPC gel permeation chromatography

HPLC high -performance liquid chromatography

HRGC high resolution gas chromatography

HSDB Hazardous Substance Data Ba nk

IARC International Agency for Research on Cancer

IDLH immediately dangerous to life and health

ILO International Labor Organization

IRIS Integrated Risk Information System

Kd adsorption ratio kg kilogram kkg metric ton

K

oc organic carbon partition co efficient

K

ow octanol- water partition coefficient

L liter

LC liquid chromatography

LC 50 lethal concentration, 50% kill

LC Lo lethal concentration, low

LD 50 lethal dose, 50% kill

LD Lo lethal dose, low

LDH lactic dehydrogenase

LH luteinizing hormone

LOAEL low est

- observed

- adverse

- effect level

LSE Levels of Significant Exposure

LT 50 lethal time, 50% kill

m meter

MA trans,trans -muconic acid

MAL maximum allowable level

mCi millicurie

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APPENDIX C

MCL maximum contaminant level

MCLG maximum contaminant level goal

MF modifying factor

MFO mixed function oxidase

mg milligram

mL milliliter

mm millimeter mmHg millimeters of mercury

mmol millimole mppcf millions of particles per cubic foot

MRL Minimal Risk Level MS mass spectrometry NAAQS National Ambient Air Quality Sta ndard

NAS National Academy of Science

NATICH National Air Toxics Information Clearinghouse

NATO North Atlantic Treaty Organization

NCE normochromatic erythrocytes

NCEH National Center for Environmental Health

NCI National Cancer Institute

ND not detected

N FPA National Fire Protection Association

ng nanogram NHANES National Health and Nutrition Examination Survey

NIEHS National Institute of Environmental Health Sciences

NIOSH National Institute for Occupational Safety and Health

NIOSHTIC NIOSH's Computerized Information Retrieval System

NLM National Library of Medicine

nm nanometer
nmol nanomole

NOAEL no- observed

- adverse

- effect level

NOES National Occupational Exposure Survey

NOHS National Occupational Hazard Survey

NPD nitrogen phosphorus detection

NPDES Nat ional 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 O ffice of Drinking Water, EPA

OERR Office of Emergency and Remedial Response, EPA

OHM/TADS Oil and Hazardous Materials/Technical Assistance Data System

OPP Office of Pesticide Programs, EPA

OPPT Office of Pollution Prevention and Toxics, EPA

OPPTS Office of Prevention, Pesticides and Toxic Substances, EPA

OR odds ratio

OSHA Occupational Safety and Health Administration

OSW Office of Solid Waste, EPA

OTS Office of Toxic Substances

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OW Office of Water

OWRS Office of Water Regulations and Standards, EPA

PAH poly cyclic aromatic hydrocarbon

PBPD physiologically based pharmacodynamic

PBPK physiologically based pharmacokinetic

PCE polychromatic erythrocytes

PEL permissible exposure limit

pg picogram

PHS Public Health Service

PID photo ionization detector pmol picomole

PMR proportionate mortality ratio ppb parts per billion ppm parts per million

ppt parts per trillion

PSNS pretreatment standards for new sources

RBC red blood cell

REL recommended exposure level/limit

RfC reference concentration

RfD reference dose

RNA ribonucleic acid RQ reportable quantity

RTECS Registry of Toxic Effects of Chemical Substances

SARA Superfund Amendments and Reauthorization Act

SCE sister chromatid exchange

SGOT serum glutamic oxaloacetic transaminase

SGPT serum glutamic pyruvic transaminase

SIC standard industrial classification

SIM selected ion monitoring

SMCL secondary maximum contaminant level

SMR standardized mortality ratio

SNARL suggested no adverse response level

SPEGL Short- Term Public Emergency Guidance Level

STEL short term exp osure limit

STORET Storage and Retrieval

TD 50 toxic dose, 50% specific toxic effect

TLV threshold limit value

TOC total organic carbon TPQ threshold planning quantity

TRI Toxics Release Inventory

TSCA Toxic Substances Control Act

TWA time

- weighted average

UF uncertainty factor

U.S. United States

USDA United States Department of Agriculture

USGS United States Geological Survey

VOC volatile organic compound

WBC white blood cell

WHO World Health Organization

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APPENDIX C

> greater than

≥ greater than or equal to

= equal to

< less than

≤ less than or equal to

% percent

α alpha β beta

γ gamma δ delta

μm micrometer

μg microgram

q 1 * cancer slope factor

– negative

+ positive (+) weakly positive result (–) weakly negative result

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APPENDIX C



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### APPENDIX D. INDEX

absorbed dose

................................................................................................ .............................................. 47

adenocarcinomas 30

................................................................................................ ................................... 10, adsorption

................................................................................................ .............................................. 65, 73

aerobic

................................................................................................ ......................................................... 75

alanine aminotransferase

............................................................................................................................. 21

ambient air 96

............................................................................................ 67, 70, 76, 77, 80, 82, 83, 85, 86,

anaerobic 76

................................................................................................ ......................................... 69, 75, aspartate aminotransferase

.......................................................................................................................... 21

bioaccumulation 85

................................................................................................ ...................................... 9, bioavailability

................................................................................................ ............................................. 85

biocon centration factor

................................................................................................ ............................... 74 biodegradation

....................................................................................................................... 9, 67, 75, 76, 85

biomarker 89

............................................................................................................................ 47, 48, 55, 86, body w eight e ffects

................................................................................................ ..................................... 29

breast milk

................................................................................................ ................................................... 83

cancer 69

................................................................................................ .................................... 4, 23, 46, 53, carcinogen

................................................................................................ ....................................... 4, 10, 103 carcinogenic

................................................................................................ 4, 10, 15, 30, 31, 37, 52, 53, 103 carcinogenicity

.............................................................................................................. 9, 10, 30, 53, 55, 103

carcinoma 30

................................................................................................ .............................................. 10, cardiac arrhythmia

................................................................................................................ 9, 13, 16, 48, 50

cardiovascular 28

................................................................................................ ....................................... 21,

cardiovascular effects 28

............................................................................................................................ 21,

chromosomal aberrations

............................................................................................................................ 32

death 23

................................................................................................ ................................................ 15, 16,

dermal effects

................................................................................................ .............................................. 29 developmental effects

................................................................................................... 13, 22, 29, 31, 54, 56

endocrine 44

................................................................................................ ......................................... 29, 43,

endocrine e ffects

................................................................................................ ......................................... 29

fe tus 45

................................................................................................ ....................................................... 44, gastrointestinal effects

................................................................................................ ................................ 28 general population

............................................................................................................................. 9, 83, 86 genotoxic

................................................................................................ ......................................... 15, 32, 53 genotoxicity

................................................................................................ ........................................... 32, 53 groundwater

.................................................................... 2, 9, 54, 67, 72, 74, 75, 76, 78, 79, 80, 85, 91, 103 growth retardation

................................................................................................ ....................................... 13

half- life 76

................................................................................................ ...................................... 47, 73, 75,

h ematological e ffects

................................................................................................ .................................. 28 hepatic e ffects

................................................................................................ ................................. 10, 21, 28 hydrolysis

................................................................................................ ...................................................... 9 hydroxyl radical

................................................................................................ .......................................... 75 immunological

................................................................................................ ...................................... 15, 22 immunological effects

................................................................................................ ................................. 22

K

ow ................................................................................................ ........................................................ 61, 85

LD 50

................................................................................................ ............................................................. 23

milk 99

................................................................................................ ....................................................... 83,

m

usculoskeletal e ffects

................................................................................................ ............................... 28 neoplastic

................................................................................................ .............................................. 23, 30

neurobehavioral

................................................................................................ ........................................... 44

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APPENDIX D

neurochemical

................................................................................................ ............................................. 54 neurological effects

................................................................................................................... 13, 22, 29, 31 neurophysio logical

................................................................................................ ...................................... 54

ocular effects

................................................................................................ ......................................... 21, 29 pharmacodynamic ....................................................................................................................................... 40 pharmacokinetic ...................................................................................................... 31, 40, 41, 42, 43, 45, 56 photolysis .............................................................................................................................................. 67, 76

rate constant

................................................................................................ ................................................ 75

renal effects

................................................................................................ ............................... 10, 13, 21 , 29 reproductive effects................................................................................................................... 22, 29, 31, 54

r espiratory e ffects

................................................................................................ ........................................ 28

retention

................................................................................................ ................................................ 89, 98 solubility

................................................................................................ ............................................... 34, 73

sys temic effects

......................................................................................................................... 21, 28, 31, 52

T3

................................................................................................ .......................................................... 17, 24 toxicokinetic.................................................................................................................................... 15, 55, 56
tumors ............................................................................................................................................. 10, 30, 31 vapor pressure ......................................................................................................................................... 9, 98 volatility

................................................................................................ .......................................... 67, 73, 96

volatilization

....................................................................................................................... 67, 73, 74, 75, 85

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