TOXICOLOGICAL PROFILE FOR
 

CHLOROETHANE
 

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
 

Public Health Service
 

Agency for Toxic Substances and Disease Registry
 

December 1998 
CHLOROETHANE II 

DISCLAIMER 

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

Agency for Toxic Substances and Disease Registry. 
CHLOROETHANE III 

UPDATE STATEMENT
 

A Toxicological Profile for chloroethane was released in December 1989. This edition supersedes any 

previously released draft or final profile. 

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

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

Agency for Toxic Substances and Disease Registry
 

Division of Toxicology/Toxicology Information Branch
 

1600 Clifton Road NE, E-29
 

Atlanta, Georgia 30333
 


vi 

*Legislative Background 

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

Reauthorization Act (SARA) of 1986 (Public Law 99-499) which amended the Comprehensive 

Environmental Response, Compensation, and Liability Act of 1980 (CERCLA or Superfund). This 

public law directed ATSDR to prepare toxicological profiles for hazardous substances most 

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

significant potential threat to human health, as determined by ATSDR and the EPA. The availability 

of the revised priority list of 275 hazardous substances was announced in the Federal Register on 

November 17, 1997 (62 FR 61332). For prior versions of the list of substances, see Federal Register 

notices dated April 29, 1996 (61 FR 18744); April 17, 1987 (52 FR 12866); October 20, 1988 (53 FR 

41280); October 26, 1989 (54 FR 43619); October 17,199O (55 FR 42067); October 17, 1991 (56 FR 

52166); October 28, 1992 (57 FR 48801); and February 28, 1994 (59 FR 9486). Section 104(i)(3) of 

CERCLA, as amended, directs the Administrator of ATSDR to prepare a toxicological profile for 

each substance on the list. 
CHLOROETHANE vii 

QUICK REFERENCE FOR HEALTH CARE PROVIDERS 

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

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

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

providers treating patients potentially exposed to hazardous substances will find the following 

information helpful for fast answers to often-asked questions. 

Primary Chapters/Sections of Interest 

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

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

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

general health effects observed following exposure. 

Chapter 2: Health Effects: Specific health effects of a given hazardous compound are reported by 

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

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

this section. 

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

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

health effects observed following exposure. 

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

issues:
 

Section 1.6 How Can (Chemical X) Affect Children?
 

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

Section 2.6 Children’s Susceptibility
 

Section 5.6 Exposures of Children
 

Other Sections of Interest:
 

Section 2.7 Biomarkers of Exposure and Effect
 

Section 2.10 Methods for Reducing Toxic Effects
 

ATSDR Information Center 

Phone: l-800-447-1544 (to be replaced by l-888-42-ATSDR in 1999)
 

or 404-639-6357 Fax: 404-639-6359
 

E-mail: atsdric@cdc.gov Internet: http://atsdrl.atsdr.cdc.gov:8080
 

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

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

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

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

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

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

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

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

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

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

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

to hazardous materials. 

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

Other Agencies and Organizations 

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

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

workplace. Contact: NCEH, Mailstop F-29,4770 Buford Highway, NE, Atlanta, GA 30341-3724 

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

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

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

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

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

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

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

Taft Laboratory, Mailstop C-19,4676 Columbia Parkway, Cincinnati, OH 45226-1998 • Phone: 800­

35-NIOSH. 

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

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

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

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

Referrals 

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

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

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

202-347-4950 • e-mail: aoec@dgs.dgsys.com • AOEC Clinic Director: 

http://occ-env/med.mc.duke.edu/oem/aoec.htm. 

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

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

medicine. Contact: ACOEM, 55 West Seegers Road, Arlington Heights, IL 60005 • Phone: 847-228­

6850 • FAX: 847-228-1856. 
CHLOROETHANE ix 

CONTRIBUTORS 

CHEMICAL MANAGER(S)/AUTHOR(S): 

G. Daniel Todd, Ph.D.
 

ATSDR, Division of Toxicology, Atlanta, GA
 

Carol Eisenmann, Ph.D.
 

Sciences International, Inc., Alexandria, VA
 

Kara B. Altshuler, Ph.D.
 

Sciences International, Inc., Alexandria, VA
 

THE PROFILE HAS UNDERGONE THE FOLLOWING ATSDR INTERNAL REVIEWS:
 

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

of each profile for consistency and accuracy in interpreting health effects and classifying end points. 

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

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

and makes recommendations for derivation of MRLs. 

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

consistency across profiles and adherence to instructions in the Guidance. 

CHLOROETHANE xi 

PEER REVIEW 

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

1. Dr. Martin Alexander, Cornell University, Ithaca, NY. 

2. Dr. Syed GhiasUddin, Toxicologist, Indiana Department of Environmental Management, Indianapolis, IN. 

3. Dr. Shane Que Hee, UCLA School of Public Health, Los Angeles, CA. 

These experts collectively have knowledge of chloroethane’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(1)( 13) of the Comprehensive Environmental Response, Compensation, 

and Liability Act, as amended. 

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

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

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

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

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

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

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









CHLOROETHANE 1 

1. PUBLIC HEALTH STATEMENT 

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

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

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

federal cleanup activities. Chloroethane has been found in at least 282 of the 1,467 current or former 

NPL sites. However, the total number of NPL sites evaluated for this substance is not known. As 

more sites are evaluated, the sites at which chloroethane is found may increase. This information is 

important because exposure to this substance may harm you and because these sites may be sources 

of exposure. 

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

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

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

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

If you are exposed to chloroethane, many factors determine whether you’ll be harmed. These 

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

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

traits, lifestyle, and state of health. 

1.1 WHAT IS CHLOROETHANE? 

Chloroethane, also called ethyl chloride, is a colorless gas at room temperature and pressure, with 

a characteristically sharp odor. People can smell chloroethane in the air at levels above 4 parts 
CHLOROETHANE 2 

1. PUBLlC HEALTH STATEMENT 

chloroethane in a million parts of air by volume (ppm). It can be smelled in water at levels above 0.02 

parts chloroethane in a million parts of water (ppm). In pressurized containers, chloroethane exists as 

a liquid. However, the liquid evaporates quickly when exposed to air. It catches fire easily and is very 

dangerous when exposed to heat or flame. Chloroethane does not occur naturally in the environment. 

It is present in the environment as a result of human activity. 

In the past, the largest single use for chloroethane was for the production of tetraethyl lead, which is a 

gasoline additive. However, production of chloroethane has decreased dramatically as a result of 

stricter government regulations controlling lead in gasoline. Other applications include use in the 

production of ethyl cellulose, dyes, medicinal drugs, and other commercial chemicals, and use as a 

solvent and refrigerant. It is used to numb skin prior to medical procedures such as ear piercing and 

skin biopsies, and it is used in the treatment of sports injuries. 

1.2 WHAT HAPPENS TO CHLOROETHANE WHEN IT ENTERS THE 

ENVIRONMENT? 

Most of the chloroethane released to the environment ends up as a gas in the atmosphere, while much 

smaller amounts enter groundwater as a result of passage through soil. Once in the atmosphere, 

chloroethane breaks down fairly rapidly by reaction with substances in the air. It takes about 40 days 

for half of any given amount of chloroethane that is released to the atmosphere to disappear. In 

groundwater, chloroethane changes slowly to ethanol and a chloride salt as a result of reaction with 

water. In addition, some types of bacteria present in the water may break down chloroethane to 

smaller compounds. However, not enough is known about chloroethane to be sure if this occurs or 

how long it may remain in groundwater. For more information, see Chapters 3,4, and 5. 

1.3 HOW MIGHT I BE EXPOSED TO CHLOROETHANE? 

Humans can be exposed to chloroethane from environmental, occupational, and consumer sources. 

During the mid-to-late 1970s and the early 1980s chloroethane was detected in samples of outdoor 

air. Air samples collected in urban and suburban areas contained 
CHLOROETHANE 3 

1. PUBLIC HEALTH STATEMENT 

chloroethane at an average level of 41-140 parts of chloroethane in a trillion parts of air (ppt; 

1 ppt is l,000,000 times less than 1 ppm). Rural air samples contained less than 5 ppt. Current 

levels of chloroethane in the air are expected to be even lower than levels found in the past 

because of the sharp decrease in chloroethane production in the United States and the decrease in 

chloroethane release. Occurrences of chloroethane in air can be attributed to releases from 

factories that manufacture or use chloroethane; evaporation from some landfills, solvents, 

refrigerants, and anesthetics; and releases in fumes from the burning of plastics and other materials 

found in trash. Based on the limited amount of information available on the occurrence of 

chloroethane in drinking water, it can be concluded that extremely low levels of chloroethane may 

occur in some drinking water supplies as a result of formation during chlorination, contamination of 

rivers and lakes used as drinking water supplies, or seepage into groundwater resulting from storage 

of chemical wastes or disposal at waste sites. However, there is not enough information available to 

indicate what levels of chloroethane occur in drinking water under these circumstances. No data were 

located that indicate that chloroethane is found in food. 

Exposure may also result from contact with various consumer products including some solvents, 

paints, and refrigerants. People may be exposed to chloroethane through skin contact as the 

result of its use as an agent to numb skin before ear piercing, before skin biopsy, as a treatment 

for sports injury, and for other medical reasons. Occupational exposure may result from 

inhalation or skin contact. Workers who may be exposed to chloroethane include physicians, 

nurses, and other medical workers, automobile mechanics, office machine mechanics, household 

appliance and accessory installers, assemblers, professional painters, heavy-equipment mechanics, 

diesel mechanics, plumbers, and pipe fitters. According to a National Institute for Occupational 

Safety and Health (NIOSH) survey conducted between 1981 and 1983, au estimated 49,212 workers 

in the United States were exposed to chloroethane in the workplace. More recent data are not 

available to determine how many workers might be exposed to chloroethane per year in the United 

States. For further information, see Chapter 5. 
CHLOROETHANE 4 

1. PUBLIC HEALTH STATEMENT 

1.4 HOW CAN CHLOROETHANE ENTER AND LEAVE MY BODY? 

Chloroethane can enter the body when a person breathes air containing chloroethane vapor. 

Chloroethane may also enter the body through the skin, although most of it quickly evaporates 

from the skin’s surface. When a person drinks water containing chloroethane, it enters the body 

through the digestive tract. After chloroethane enters the body, it may leave the body through the 

lungs. Some chloroethane may also be changed to acetate, which is normally found in the body. 

Other chemicals formed from chloroethane leave the body in the urine. 

People who happen to be near hazardous waste sites containing chloroethane are most likely to be 

exposed to the compound by breathing potentially contaminated air. People may also be exposed 

to chloroethane by drinking potentially contaminated water. See Chapter 2 for more information. 

1.5 HOW CAN CHLOROETHANE AFFECT MY HEALTH? 

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

who have been harmed, scientists use many tests. 

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

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

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

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

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

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

strict animal care guidelines. 

Brief exposure to high levels of chloroethane vapor can produce temporary feelings of drunkenness, 

and at still higher levels, lack of muscle coordination and unconsciousness. Adults have felt dizzy and 

have suffered decreased reaction times as a result of inhaling chloroethane. They have 
CHLOROETHANE 5 

1. PUBLIC HEALTH STATEMENT 

also experienced stomach cramps, nausea, vomiting, and eye irritation after breathing high 

concentrations of chloroethane for a short time. 

Workers who breathed chloroethane vapors for 1.5 to 3 years (levels of chloroethane unknown) 

had significantly decreased defensive responses against illness. Inhalant abusers who intentionally 

breathe chloroethane vapors at much higher concentrations than those found in any work environment 

or near any hazardous waste site have experienced these neurological effects. Long term abuse of 

high chloroethane concentrations causes the most adverse effects of chloroethane exposure, namely, 

those to the nervous system. In the worst recorded cases of chloroethane abuse by sniffing, the 

abusers have had severe symptoms including jerking eye movements, an inability to control muscles 

in voluntary movements, difficulty in speaking clearly, an inability to perform finger tapping 

exercises, sluggish lower limb reflexes, seizures, difficulties in walking, disorientation, short-term 

memory loss, and hallucinations affecting their sight and hearing. In one case, damage to motor and 

sensory nerves occurred. 

Human patients have died after breathing chloroethane concentrations high enough to induce 

anesthesia. Dogs have suffered irregular heart rhythms, followed by death, when given anesthetic 

doses of chloroethane. Due to the risk of accidental death, chloroethane is no longer medically 

used as a general anesthetic during major surgery. Chloroethane can, however, be applied to the 

skin in the form of chloroethane spray as a numbing agent prior to minor surgery. If this spray is 

applied for too long, frostbite can result. Some adults have had allergic reactions to the 

chloroethane spray while others experienced mild pain after being sprayed for 10 seconds. 

Studies have shown that chloroethane can enhance the effects of alcohol in rats. It is unknown if 

similar interactions between chloroethane and alcohol occur in humans. 

It is not known whether chloroethane produces cancer in humans. However, long-term exposure 

to high levels of chloroethane vapor has been shown to produce cancer in mice. There have been 

no animal or human studies involving the ability of chloroethane to cause cancer when either eaten or 

applied to the skin. The International Agency for Research on Cancer (IARC) has reviewed 
CHLOROETHANE 6 

1. PUBLIC HEALTH STATEMENT 

the information available concerning the abiIity of chloroethane to cause cancer. They concluded 

that chloroethane is not classifiable as to its carcinogenicity in humans. See Chapter 2 for more 

information. 

1.6 HOW CAN CHLOROETHANE AFFECT CHILDREN? 

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

to maturity at 18 years of age in humans. Potential effects on children resulting from exposures of 

the parents are also considered. 

There are no known unique exposure pathways by which children may be exposed to chloroethane. 

In children, there have been few recorded reports of exposures to chloroethane or adverse health 

effects resulting from this exposure. Brief inhalation exposure of children to very high 

concentrations of chloroethane has resulted in stimulation of certain nerves followed by a decrease in 

heart rate. One teenager died from lung paralysis during general anesthesia with chloroethane. In 

addition to these health effects seen specifically in children, the observed adverse effects of 

chloroethane exposure in adults are also expected in children. It is unknown whether children differ 

from adults in their susceptibility to health effects from chloroethane exposure. 

We do not know whether chloroethane exposure can affect development in humans. There is not 

enough information to know whether chloroethane affects development in animals. Only one 

developmental study has been done in animals. This study with mice showed that exposure to 

high levels of chloroethane during pregnancy delayed bone development in the offspring. 

We do not know whether chloroethane or its breakdown products within the body can reach and 

cross the mother’s placenta into her developing baby. One study has shown that chloroethane can 

be found in mother’s milk, but we do not know if the mothers were exposed to the compound by 

breathing it, eating it, or having it sprayed on their skin. 
CHLOROETHANE 7 

1. PUBLIC HEALTH STATEMENT 

1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO

 CHLOROETHANE? 

If your doctor finds that you have been exposed to significant amounts of chloroethane, ask if 

children may also be exposed. When necessary your doctor may need to ask your state 

Department of Public Health to investigate. 

Little information exists concerning the concentrations of chloroethane that might be present in 

drinking water. However, past data indicate that chloroethane is not a frequent contaminant in 

drinking water, and therefore the risk to families from drinking water containing chloroethane is 

low. 

Chloroethane is found in common household products such as paints, solvents, air fresheners, and 

deodorant sprays. Inhaling or ingesting toxic amounts of chloroethane from these products is 

possible. Therefore, household products such as these should be stored out of reach of young 

children to prevent accidental poisonings. Always store household chemicals in their original 

labeled containers; never store household chemicals in containers children would find attractive to eat 

or drink from, such as old soda bottles. Keep your Poison Control Center’s number by the 

phone. 

Sometimes older children sniff household chemicals in an attempt to get high. Chloroethane is 

sold in drug paraphernalia shops as Ethyl Gaz, Ethyl Four Star, Black Jac, and Maximum Impact. 

Your children may be exposed to chloroethane by inhaling products containing it and are putting 

their health at serious risk if they do so. Talk with your children about the dangers of sniffing 

chemicals. 

When household products that contain chloroethane are used properly and are not abused, the 

concentrations of chloroethane within them are not high enough to pose a risk of significant 

exposure to children. 
CHLOROETHANE 8 

1. PUBLIC HEALTH STATEMENT 

The tendency of chloroethane to evaporate upon contact with air makes it highly unlikely that the 

compound could be taken home on the parents’ work clothes. 

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

 EXPOSED TO CHLOROETHANE? 

Although there are complex analytical tests that chemists use to measure chloroethane in the 

blood, milk, or urine, there are no commonly used medical tests available to determine whether or 

not a person has been exposed to chloroethane. A breath test to determine exposure may be 

possible but is not commonly used. 

1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT

 MADE TO PROTECT HUMAN HEALTH? 

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

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

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

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

provide valuable guidelines to protect public health but cannot be enforced by law. Federal 

organizations that develop recommendations for toxic substances include the Agency for Toxic 

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

Health (NIOSH). 

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

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

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

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

other factors. 
CHLOROETHANE 9 

1. PUBLIC HEALTH STATEMENT 

Recommendations and regulations are also periodically updated as more information becomes 

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

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

Chloroethane levels in the workplace are regulated by QSHA. The occupational exposure limit 

for an g-hour work day of a 40-hour work week is 1,000 ppm. The EPA requires industry to 

report discharges or spills of 100 pounds or more. See Chapter 7 for more information. 

1.10 WHERE CAN I GET MORE INFORMATION? 

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

environmental quality department or 

Agency for Toxic Substances and Disease Registry 

Division of Toxicology 

1600 Clifton Road NE, Mailstop E-29 

Atlanta, GA 30333 

* Information line and technical assistance 

Phone: l-800-447- 1544
 

Fax: (404) 639-6359
 

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

These clinics specialize in recognizing, evaluating, and treating illnesses resulting from 

exposure to hazardous substances. 

* To order toxicological nrofnes. contact 

National Technical Information Service
 

5285 Port Royal Road
 

Springfield, VA 22161
 

Phone: (800) 553-6847 or (703) 487-4650
 

CHLOROETHANE 11 

2. HEALTH EFFECTS 

2.1 INTRODUCTION 

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

other interested individuals and groups with an overall perspective of the toxicology of chloroethane. 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. 

2.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE 

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

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

oral, and dermal; and then by health effect-death, systemic, immunological, neurological, reproductive, 

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

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

Levels of significant exposure for each route and duration are presented in tables and illustrated in figures. The points 

in the figures showing no-observed-adverse-effect levels (NOAELs) or lowest-observed-adverseeffect levels 

(LOAELs) reflect the actual doses (levels of exposure) used in the studies. LOAELS have been classified into “less 

serious” or “serious” effects. “Serious” effects are those that evoke failure in a biological system and can lead to 

morbidity or mortality (e.g., acute respiratory distress or death). “Less serious” effects are those that are not expected 

to cause significant dysfunction or death, or those whose significance to the organism is not entirely clear. ATSDR 

acknowledges that a considerable amount of judgment may be required in establishing whether an end point should be 

classified as a NOAEL, “less serious” LOAEL, or “serious” LOAEL, and that in some cases, there will be insufficient 

data to decide whether the effect is indicative of significant dysfunction. However, the Agency has established 

guidelines and policies that are used to classify these end points. ATSDR believes that there is sufficient merit in this 

approach to warrant anattempt at distinguishing between “less serious” and “serious” effects. The distinction 

between “less serious” effects and “serious” effects is considered to be important because it helps the users of the 

profiles to identify levels of exposure at which major health effects start to appear LOAELs or NOAELs should also 

help in 
CHLOROETHANE 12 

2. HEALTH EFFECTS 

determining whether or not the effects vary with dose and/or duration, and place into perspective the 

possible significance of these effects to human health. 

The significance of the exposure levels shown in the Levels of Significant Exposure (LSE) tables and 

figures may differ depending on the user’s perspective. Public health officials and others concerned with 

appropriate actions to take at hazardous waste sites may want information on levels of exposure associated 

with more subtle effects in humans or animals (LOAEL) or exposure levels below which no adverse 

effects (NOAELs) have been observed. Estimates of levels posing minimal risk to humans (Minimal Risk 

Levels or MRLs) may be of interest to health professionals and citizens alike. 

Levels of exposure associated with carcinogenic effects (Cancer Effect Levels, CELs) of chloroethane are 

indicated in Table 2- 1 and Figure 2-l. 

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

made for chloroethane. An MRL is defined as an estimate of daily human exposure to a substance that is 

likely to be without an appreciable risk of adverse effects (noncarcinogenic) over a specified duration of 

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

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

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

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

methodology does not exist to develop MRLs for dermal exposure. 

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

uncertainties are associated with these techniques. Furthermore, ATSDR acknowledges additional 

uncertainties inherent in the application of the procedures to derive less than lifetime MRLs. As an 

example, acute inhalation MRLs may not be protective for health effects that are delayed in development 

or are acquired following repeated acute insults, such as hypersensitivity reactions, asthma, or chronic 

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

significant human exposure improve, these MRLs will be revised. 

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

interpretation of the tables and figures for Levels of Significant Exposure and the MRLs. 
CHLOROETHANE 13 

2. HEALTH EFFECTS 

2.2.1 Inhalation Exposure 

Some of the data on the health effects of chloroethane following inhalation exposure were taken from a 

study by Troshina (1966). This report does not provide an adequate description of experimental methods 

or results. Consequently, the results of the study are not included in Table 2-l or plotted in Figure 2-l as 

levels of significant exposure. 

2.2.1.2 Death 

Use of chloroethane as a general anesthetic has occasionally resulted in the death of human patients 

(Konietzko 1984; Kuschinsky 1970; Lawson 1965; Lehman and Flury 1943). In the years between 1945 

and 1964, there were 71 deaths attributed to chloroethane inhalation in the United Kingdom (Dawkins 

1964). Only chloroform has been blamed for more anesthetic deaths than chloroethane (Lawson 1965). 

Death from respiratory paralysis (Kuschinsky 1970) and toxic injury to the heart (Lehman and Flury 1943) 

have been reported following anesthesia with chloroethane. Death of a man following abuse of 

chloroethane has also been reported (Yacoub et al. 1993). Although the blood concentration of 

chloroethane was 65 mg/dL in this man shortly after death, the study authors believed that because of 

resuscitation attempts for about 65 minutes, concentrations of chloroethane resulting in death were 

actually greater than the measured concentration. Levels of significant exposure are not reported in Table 

2- 1 or plotted in Figure 2- 1 because concentrations of chloroethane lethal to humans are not known. 

Mortality produced by inhalation of high concentrations of chloroethane vapor has been studied 

quantitatively in animals. The minimum lethal concentration of chloroethane in a 2-hour exposure study in 

mice was 56,860 ppm (Lazarew 1929). In another 2-hour exposure test, the minimum lethal concentration 

was 54,948 ppm in rats and mice (Troshina 1966). In this case, death was probably caused by 

asphyxiation. Exposure to 19,000 ppm chloroethane for 4 hours did not produce mortality in rats or mice 

(NTP 1989). The lethal concentration of chloroethane increased as the duration of exposure decreased in 

guinea pigs exposed to chloroethane concentrations ranging from 0 to 241,000 ppm for 5 minutes to 13.5 

hours (Sayers et al.1929). Exposure to 20,000 ppm chloroethane for 9 hours was not lethal to guinea pigs 

in this study. Death was reported during or after exposure of guinea pigs to 40,000 ppm for 9 hours (2/6), 

87,000 ppm for 4.5 hours (6/6), 76,000 ppm for 90 minutes (4/4), and 51,000 ppm for 40 minutes (l/3). 















CHLOROETHANE 29 

2. HEALTH EFFECTS 

Studies in which animals were repeatedly exposed to chloroethane for 14 days or less did not report deaths 

resulting from inhalation of this compound. No mortality was reported in rats exposed to 436 ppm 4 

hours/day for 8 exposures in 10 days (Gohlke and Schmidt 1972; Schmidt et al. 1972), in mice exposed to 

4,843 ppm 23 hours/day for 11 days (Landry et al. 1987, 1989), in rats and dogs exposed to 9,980 ppm 6 

hours/day, 5 days/week for 2 weeks (Landry et al. 1982) or in rats and mice exposed to 19,000 ppm 6 

hours/day, 5 days/week for 2 weeks (NTP 1989). 

Mortality was not increased significantly by chloroethane exposure in studies of intermediate duration 

(15-364 days). Mortality was not observed in rats or mice exposed to chloroethane at 19,000 ppm 

6 hours/day, 5 days/week for 13 weeks (NTP 1989). At 10,000 ppm, 1 male mouse died. No discussion 

was provided on whether or not this death was exposure related. Therefore, this death is not included in 

Table 2-l or Figure 2- 1. 

In a chronic inhalation study, rat survival was not reduced compared to controls following exposure to 

15,000 ppm chloroethane 6 hours/day, 5 days/week for 1102 weeks (NTP 1989). The concurrent controls, 

however, had abnormally low survival rates after week 90 of the study. Survival was significantly reduced 

in mice following exposure to 15,000 ppm chloroethane for 100 weeks; the effect was found in males after 

330 days and in females after 574 days (NTP 1989). An ascending urinary tract infection may have 

contributed to the reduced survival in male mice. The decreased survival in female mice was attributed to 

uterine cancer. 

All LOAEL values from each reliable study for death in each species and duration category are recorded in 

Table 2-l and plotted in Figure 2-l. 

2.2.1.2 Systemic Effects 

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

species and duration category are recorded in Table 2-l and plotted in Figure 2-l. The results of the study 

by Troshina (1966) were not used as levels of significant exposure because experimental methods and 

results were not described in sufficient detail. 
CHLOROETHANE 30 

2. HEALTH EFFECTS 

Respiratory Effects. Chloroethane in combination with nitrous oxide and oxygen was used to 

maintain anesthesia in human patients previously made unconscious by administration of either 

thiopentone (thiopental), nitrous oxide, or a mixture of nitrous oxide, chloroethane, and oxygen (Cole 

1956). A concentration of 20,000 ppm chloroethane was initially required to maintain anesthesia, but this 

could slowly be reduced to as low as 5,000 ppm in some cases. Respiration usually remained smooth and 

even, but some cases of tachypnea were seen. Respiratory rate was stimulated in 16 of 23 patients tested in 

a second similar study using 36,000 ppm chloroethane (Cole 1967). This study was not reported in Table 

2-l or plotted in Figure 2- 1 as a NOAEL or LOAEL for the acute respiratory effects of chloroethane in 

humans because the compound was administered in conjunction with other anesthetic agents. Respiratory 

paralysis was reported to be the cause of death of a 14-year-old child who died during anesthesia with 

chloroethane (Kuschinsky 1970). A level of significant exposure was not based on this report because the 

concentration of chloroethane administered was not known. 

Studies in animals also indicate that inhalation of chloroethane may affect respiration. Exposure to 10 ppm 

chloroethane for 10 minutes had no consistent effect on the respiratory rate of rabbits (Watanabe 1983). 

This study was not used as the basis for a NOAEL because changes in respiratory rate occurred, even 

though no trend was found. Inhalation of 20,000 ppm chloroethane for 9 hours resulted in only very mild 

tissue changes, but congestion, hemorrhage, and edema were found in the lungs of guinea pigs that died 

following exposure to 40,000 ppm or more (Sayers et al. 1929). 

Hypertrophic bronchial tubes and interstitial pneumonia were found in rats given eight 4-hour exposures to 

436 ppm chloroethane; however, these effects were also present to a lesser extent in controls (Gohlke and 

Schmidt 1972). Consequently, these results were not considered to be indicative of adverse respiratory 

effects produced by chloroethane. The only other respiratory effect reported by this study was a mild 

transitory increase in relative lung weight, which was also not considered adverse (Schmidt et al. 1972). 

Absolute and relative lung weights were not affected in rats or mice exposed to chloroethane at 15,000 

ppm 6 hours/day for 5 days (Fedtke et al. 1994a). Histopathological changes were not observed in the 

respiratory tracts of mice exposed to chloroethane at 4,843 ppm 23 hours/day for 11 days (Landry et al. 

1987,1989). Histopathological examinations of respiratory organs and tissues were performed following 

inhalation of chloroethane for 6 hours/day, 5 days/week for 2 weeks at a concentration of 9,980 ppm in 

rats and dogs (Landry et al. 1982) and 19,000 ppm in rats and mice (NTP 1989). No effects were reported 

in either study 
CHLOROETHANE 31 

2. HEALTH EFFECTS 

The NTP (1989) study is limited in that organs of only 3 of 10 exposed rats and 3 of 10 exposed mice were 

examined microscopically. Therefore, this study is not presented in Table 2-l or Figure 2-l for respiratory 

effects. 

In an intermediate-duration study, inhalation of 19,000 ppm cbloroethane for 13 weeks (6 hours/day, 

5 days/week) failed to produce lesions in the respiratory tissue of rats or mice as documented by complete 

histopathological examinations (NTP 1989). Inhalation of 216 ppm chloroethane for 6 months (4 

hours/day, 6 days/week) caused thickening of the alveolar septa in the lungs of rats; the effect was 

produced by an increase in the number of macrophages (Troshina 1966). No respiratory effects were 

reported at 22.7 ppm. 

Chronic exposure to 15,000 ppm chloroethane for approximately 2 years (6 hours/day, 5 days/week) had 

no non-neoplastic histopathological effects on the respiratory system in rats or mice (NTP 1989). 

Cardiovascular Effects. There is some evidence that inhalation of chloroethane has cardiovascular 

effects in humans. Vagal stimulation followed by direct depression of cardiac tissues was reported in 

children exposed briefly to high concentrations of chloroethane (Bush et al. 1952). This study was not 

reported in Table 2-l or plotted in Figure 2-l because the effective concentration of chloroethane was not 

reported. A mixture of chloroethane, nitrous oxide, and oxygen was used to maintain anesthesia in patients 

previously made unconscious by administration of thiopentone (thiopental), or nitrous oxide, or the 

mixture described above (Cole 1956). A concentration of 20,000 ppm chloroethane was initially required 

to maintain anesthesia, but this could slowly be reduced to concentrations as low as 5,000 ppm in some 

cases. Pulse rate remained strong and no clinically detectable arrhythmias or changes in heart rate were 

observed. A similar study using 36,000 ppm chloroethane found increased systolic blood pressure and 

pulse rate in 16 of 25 patients tested, but again no cardiac arrhythmias were detected (Cole 1967). This 

study was not reported in Table 2-l or plotted in Figure 2- 1 as a NOAEL or LOAEL for the acute 

cardiovascular effects of chloroethane in humans because the compound was administered in conjunction 

with other anesthetic agents. 

The cardiovascular effects of chloroethane have also been studied in animals. In dogs, acute exposure to 

anesthetic concentrations of chloroethane resulted in cardiac irregularities, including ventricular 

tachycardia and asystole (Haid et al. 1954; Morris et al. 1953). Chloroethane also sensitized the heart to 

the effects of epinephrine (Haid et al. 1954; Morris et al. 1953). Bush et al. (1952) found that cardiac 

depression occurred in dogs given anesthetic doses of chloroethane. This depression was initially due to 

stimulation of the vagus 
CHLOROETHANE 32 

2. HEALTH EFFECTS 

nerve and occurred within 2 minutes of the onset of anesthesia. Direct depression of the cardiac tissue 

followed and was succeeded by ventricular fibrillation and asystole, which resulted in death. None of the 

above studies are presented in Table 2-1 or plotted in Figure 2-l because effective chloroethane 

concentrations were not reported. 

Rabbits exposed to 10 ppm chloroethane for 10 minutes did not experience consistent changes in blood 

pressure or heart rate (Watanabe 1983). Although changes in these variables did occur, this study was not 

used as the basis for a NOAEL because no trend was found. The occurrence of undescribed “vascular 

disarrangements” was reported in rats and mice killed by exposure to over 54,948 ppm chloroethane for 2 

hours (Troshina 1966). Degeneration of heart muscle was found in guinea pigs that died following 

exposure to 40,000 ppm chloroethane for 9 hours (Sayers et al. 1929). No effects were reported at lower 

concentrations. 

Multiple-exposure studies of acute duration reported no significant cardiovascular effects. Rat heart weight 

was not affected by eight 4-hour exposures to 436 ppm chloroethane over a 10-day period (Schmidt et 

al.1972). When histopathological examination of rats and dogs exposed to 9,980 ppm chloroethane for 2 

weeks (6 hours/day, 5 days/week) was done, no cardiovascular effects were found (Landry et al. 1982). 

Changes in heart weights and microscopic changes in the heart were not observed in mice exposed to 

chloroethane at 4,843 ppm 23 hours/day for 11 days (Landry et al. 1987,1989). Microscopic examination 

of the heart in 3 of 10 rats and 3 of 10 mice exposed to chloroethane at 19,000 ppm 6 hours/day, 5 

days/week for 2 weeks, did not reveal any effects (NTP 1989). Because histopathological examinations 

were completed on only a few animals, this study is not presented in Table 2-l and Figure 2-l for 

cardiovascular effects. 

Inhalation of 19,000 ppm chloroethane 6 hours/day, 5 days/week for 13 weeks, had no histopathological 

effect on the cardiovascular system of rats or mice (NTP 1989). Arterial blood pressure 24 mmHg below 

controls was reported in rats exposed 4 hours/day, 6 days/week for 6 months, to 2 16 ppm chloroethane 

(Troshina 1966). No effects on blood pressure were noted at 22.7 ppm. 

In the only chronic inhalation study of chloroethane, histopathological examinations of the heart did not 

reveal any effects in rats or mice exposed to 15,000 ppm 6 hours/day, 5 days/week for approximately 2 

years (NTP 1989). 
CHLOROETHANE 33 

2. HEALTH EFFECTS 

Gastrointestinal Effects. Gastrointestinal effects have been reported in humans exposed to 

chloroethane by inhalation. Sayers et al. (1929) reported that mild abdominal cramps occurred in healthy 

human subjects who inhaled 2 breaths of 40,000 ppm chloroethane or 2-4 breaths of 20,000 ppm 

chloroethane. Exposure to 33,600 ppm chloroethane caused nausea and vomiting in human subjects after 

approximately 8 minutes; subjects exposed to 25,000 ppm did not become nauseated even after 21 minutes 

(Davidson 1925). Vomiting occurred in 10 of 23 patients who were anesthetized with 36,000 ppm 

chloroethane combined with nitrous oxide and oxygen (Cole 1967). A LOAEL was not reported in Table 

2-l or plotted in Figure 2-l because chloroethane was administered in conjunction with other anesthetic 

agents. 

Gastrointestinal effects in animals were studied by necropsy and histopathological examination. 

Congestion of the intestines was found in guinea pigs that died following exposure to 80,000 ppm for up to 

4.5 hours (Sayers et al. 1929). Chloroethane concentrations below 40,000 ppm did not produce 

gastrointestinal effects in this study. 

Exposure to 9,980 ppm chloroethane for 2 weeks had no histopathological effects on the gastrointestinal 

organs of rats or dogs (Landry et al. 1982). Histopathological changes were not observed in the 

gastrointestinal tracts of mice exposed to chloroethane at 4,843 ppm 23 hours/day for 11 days (Landry et 

al.1987, 1989), or in rats or mice exposed to 19,000 ppm 6 hours/day, 5 days/week for 2 weeks (NTP 

1989). The NTP (1989) study is not presented in Table 2-l or Figure 2-l for gastrointestinal effects because 

histopathological examinations were completed on only 3 of 10 exposed rats and 3 of 10 exposed mice. 

No gastrointestinal effects were found by histopathological examination in longer term studies. 

Chloroethane concentrations of 19,000 ppm for 13 weeks (6 hours/day, 5 days/week) in rats and mice and 

15,000 ppm for approximately 2 years (6 hours/day, 5 days/week) in rats and mice (NTP 1989) were all 

without effect on this organ system. 

Hematological Effects. There was a single report of a hematological effect following chloroethane 

inhalation in humans. A human subject exposed to 33,600 ppm chloroethane developed cyanosis within 

8.5 minutes but only when the chloroethane was not mixed with oxygen (Davidson 1925). Therefore, this 

effect was probably due to lack of oxygen, and this result was not used as the basis for a LOAEL. 

No effects on hematologic parameters (packed cell volume, hemoglobin, red blood cell counts, platelet 

counts, differential leukocyte counts, mean corpuscular volume, mean corpuscular hemoglobin) were 

noted in 
CHLOROETHANE 34 

2. HEALTH EFFECTS 

mice exposed to chloroethane at 4,843 ppm 23 hours/day for 11 days (Landry et al. 1987, 1989), or in rats 

or dogs exposed to 9,980 ppm 6 hours/day, 5 days/week for 2 weeks (Landry et al. 1982). Hematologic 

effects were not examined in other inhalation studies of chloroethane. 

Musculoskeletal Effects. No studies were located regarding musculoskeletal effects in humans 

following inhalation exposure to chloroethane. 

Histopathological examination of muscle and bone following exposure of mice to chloroethane at 4,843 

ppm 23 hours/day for 11 days did not reveal any effects (Landry et al. 1987, 1989). Histopathologic 

changes in muscle and bone were also not observed in rats or dogs exposed to chloroethane at 9,980 ppm 6 

hours/day, 5 days/week for 2 weeks (Landry et al. 1982). Rats and mice exposed to 15,000 ppm 

chloroethane 6 hours/day, 5 days/week for approximately 2 years, were also examined; no increase in the 

occurrence of bone lesions was found (NTP 1989). The National Toxicology Program (NTP) studies of 

shorter duration did not include examination of bone or muscle tissue. 

Hepatic Effects. In a case report of a woman who sniffed chloroethane (about 200-300 ml/day) for 

4 months, an enlarged liver and mild transient disturbance of liver function which was not further 

described were noted (Hes et al. 1979). The woman had previously used other drugs but was reported to be 

free of addiction for 2 years before starting to use chloroethane. Moderately elevated serum alanine 

aminotransferase was observed in a man who abused chloroethane for 30 years (Nordin et al. 1988). 

During the 4 months before the man was examined he inhaled at least 100 ml/day chloroethane (Nordin et 

al. 1988). This subject also had a history of alcohol and sedative abuse, so it is not known for certain if the 

liver effects were a result of the chloroethane abuse. 

Hepatic effects in animals have been studied by a number of researchers. A single 5minute exposure to an 

unspecified concentration of chloroethane produced an increase in the ratio of adenosine 

triphosphate/adenosine diphosphate (ATP/ADP) in the livers of mice (Oura et al. 1966). The effective 

concentration of chloroethane in this study was not reported, so no level of significant exposure was 

determined. Pale appearance, edema, congestion, and degeneration were seen in the livers of guinea pigs 

exposed to at least 20,000 ppm chloroethane for up to 9 hours (Sayers et al. 1929). Liver non-protein 

sulfhydryl (NPSH) concentration was reduced in both rats and mice following a single 6-hour exposure to 

chloroethane concentrations of 9,980 ppm for rats and 4,000 ppm for mice, but the study authors 

considered this effect to 
CHLOROETHANE 35 

2. HEALTH EFFECTS 

be more adaptive than toxicologic since the change was small and no associated liver lesions were found 

(Landry et al. 1982). 

Following 5 daily 6-hour exposures to chloroethane at 15,000 ppm, glutathione levels in the liver were 

reduced in male rats but not in female rats or in mice of either sex (Fedtke et al. 1994b). Liver weights 

were not affected in rats or mice following 5 daily 6-hour exposures to chloroethane at 15,000 ppm 

(Fedtke et al.1994a). 

Serum amino transaminase activity (alanine and aspartate), liver enzyme activity, lipid content, 

histopathology, and liver weight were not significantly altered in rats given eight 4-hour exposures to 

436 ppm chloroethane (Gohlke and Schmidt 1972; Schmidt et al. 1972). Histopathological effects were 

reported but apparently only in groups pre-treated with ethanol. It did not appear that significant tissue 

changes occurred in rats exposed to chloroethane alone. Mice exposed to 4,843 ppm chloroethane 23 

hours/day for 11 days had increased relative liver weight and slightly increased hepatocellular vacuolation 

(Landry et al. 1987, 1989). The study authors considered these effects to be mild and not indicative of 

significant toxicity. No changes in liver weight were noted in mice exposed to chloroethane at 4,946 ppm 

6 hours/day on gestation days 6-15 and sacrificed on gestation day 18 (Scortichini et al. 1986). There was 

a slight increase in relative liver weight in male rats exposed to 3,980 ppm or more for 6 hours/day, 5 

days/week for 2 weeks, but since no other hepatic effects were reported, this effect was not thought to 

indicate significant liver toxicity (Landry et al. 1982). There were no hepatic effects in dogs exposed to 

9,980 ppm chloroethane 6 hours/day, 5 days/week for 2 weeks (Landry et al. 1982). No significant 

hepatotoxicity was observed in rats or mice examined histopathologically following exposure to 19,000 

ppm chloroethane 6 hours/day, 5 days/week for 2 weeks (NTP 1989). The NTP (1989) study is not 

presented in Table 2-l or Figure 2-l for hepatic effects because histopathological examinations were 

completed on only 3 of 10 exposed rats and 3 of 10 exposed mice. 

Liver weight and histopathologic changes in the liver were not observed in mice exposed to 15,000 ppm 

chloroethane 6 hours/day for 21 days (Bucher et al. 1995). Relative liver weights were significantly 

(p<0.05) increased in male rats but not female rats or mice of either sex exposed to 19,000 ppm 

chloroethane 6 hours/day, 5 days/week for 13 weeks (NTP 1989). Because histopathological changes were 

not observed, the increased relative liver weight is not considered adverse. Interference with hepatic 

function in rats, as indicated by reduced hippuric acid elimination following sodium benzoate loading, 

occurred following both a 60-day exposure to 5,305 ppm chloroethane and a 6-month exposure to 216 

ppm (Troshina 1966). Fatty 
CHLOROETHANE 36 

2. HEALTH EFFECTS 

degeneration of hepatocytes also occurred following a 6-month exposure to 216 ppm chloroethane 

(Troshina 1966). 

Chronic exposure to 15,000 ppm chloroethane 6 hours/day, 5 days/week for approximately 2 years, 

produced no increase in the incidence of non-neoplastic hepatic lesions in rats or mice (NTP 1989). 

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

exposure to chloroethane. 

Inhalation of chloroethane has been shown to produce renal effects in animals. Pale appearance, 

congestion, and degeneration were seen in the kidneys of guinea pigs exposed to 40,000 ppm or more for 

up to 9 hours (Sayers et al. 1929). No effects were found following exposure to 20,000 ppm for 9 hours. 

Exposure to 436 ppm chloroethane for 4 hours/day for 8 days had no effect on rat kidney histopathology, 

fat content, or weight (Gohlke and Schmidt 1972; Schmidt et al 1972). Inhalation of 4,843 ppm 23 

hours/day for 11 days did not produce renal effects detectable by serum chemistry analysis or 

histopathological examination in mice (Landry et al. 1987, 1989). Absolute and relative kidney weights 

were not affected in rats or mice exposed to 15,000 ppm chloroethane for 5 daily 6-hour exposures (Fedtke 

et al. 1994a). Blood urea nitrogen (BUN) was decreased slightly in female rats following inhalation of at 

least 3,980 ppm for 2 weeks (Landry et al. 1982). However, the study authors did not consider this effect 

to be toxicologically significant since BUN is not a direct indicator of toxicity and no associated 

pathological lesions were found. No other renal effects were found in rats or dogs exposed to 9,980 ppm 

chloroethane 6 hours/day, 5 days/week for 2 weeks (Landry et al. 1982). Histopathological examination of 

3 of 10 exposed rats and 3 of 10 exposed mice showed no evidence of nephrotoxicity after exposure to 

19,000 ppm 6 hours/day, 5 days/week for 2 weeks (NTP 1989). Because of the small number of animals 

examined microscopically, this study is not presented in Table 2-l or Figure 2-l for renal effects. 

Exposure to 19,000 ppm chloroethane 6 hours/day, 5 days/week for 13 weeks, had no effect on the 

occurrence of kidney lesions in rats or mice (NTP 1989). Inhalation of chloroethane for 6 months 

increased urinary amino acid levels in the rat (Troshina 1966). The concentration at which this effect 

occurred is not stated. Therefore, a concentration is not presented in Table 2-l or Figure 2-l. 
CHLOROETHANE 37 

2. HEALTH EFFECTS 

Chloroethane vapor at a concentration of 15,000 ppm produced signs of mild nephrotoxicity in mice 

exposed 6 hours/day, 5 days/week for 100 weeks (NTP 1989). There was an increase in the incidence of 

scattered foci of tubular regeneration and minimal glomerulosclerosis in treated female mice, while treated 

male mice exhibited only slight enlargement of renal tubular cell nuclei. No renal effects were found in 

rats exposed to 15,000 ppm chloroethane 6 hours/day, 5 days/week for 102 weeks (NTP 1989). 

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

inhalation exposure to chloroethane. 

No effects on thyroid weight, thyroid histopathology, or adrenocorticotropic hormone activity were noted 

in rats exposed to 436 ppm chloroethane 4 hours/day for 8 exposures over 10 days (Gohlke and Schmidt 

1972;Schmidt et al. 1972). Histopathologic changes were not observed in the adrenals, pancreas, 

parathyroid, pituitary, or thyroid glands of mice exposed to 4,843 ppm chloroethane 23 hours/day for 11 

days (Landry et al. 1987, 1989), or rats or dogs exposed to 9,980 ppm chloroethane 6 hours/day, 5 

days/week for 2 weeks (Landry et al. 1982). Microscopic examination of the adrenals, pancreas, 

parathyroid, pituitary, and thyroid glands from 3 of 10 rats and 3 of 10 mice exposed to 19,000 ppm 

chloroethane 6 hours/day, 5 days/week for 2 weeks, did not reveal any effects (NTP 1989). Because 

histopathological examinations were completed on only a few animals, this study is not presented in Table 

2-l and Figure 2-l for endocrine effects. 

Histopathologic changes were not observed in the adrenals, pancreas, parathyroid glands, pituitary, or 

thyroid glands of rats or mice exposed to 19,000 ppm chloroethane 6 hours/day, 5 days/week for 13 

weeks, or those exposed to 15,000 ppm 6 hours/day, 5 days/week for approximately 2 years (NTP 1989). 

Dermal Effects. No studies were located regarding dermal effects in humans following inhalation 

exposure to chloroethane. 

Dermal effects following inhalation exposure to chloroethane were not reported in animal studies. No 

histopathological effects on the skin were found in mice exposed to 4,843 ppm 23 hours/day for 11 days 

(Landry et al. 1987, 1989); in rats or dogs exposed to 9,980 ppm 6 hours/day, 5 days/week for 2 weeks 

(Landry et al. 1982); or rats or mice exposed 6 hours/day, 5 days/week to 19,000 ppm for 2 weeks (NTP 

1989), 19,000 ppm for 13 weeks (NTP 1989), or 15,000 ppm for approximately 2 years. The 2-week NTP 

(1989) study is not presented in Table 2-1 or Figure 2-B for dermal effects because histopathological 

examinations were completed on only 3 of 10 exposed rats and 3 of 10 exposed mice. 
CHLOROETHANE 38 

2. HEALTH EFFECTS 

Ocular Effects. Mild eye irritation occurred in volunteers exposed briefly to 40,000 ppm 

chloroethane (Sayers et al. 1929). No eye irritation was reported followmg exposure to 20,000 ppm. 

Additional reports of eye irritation in humans during exposure to cbloroethane vapor were not identified. 

Histopathological examinations of the eyes did not reveal any effects in mice exposed to 4,843 ppm 

chloroethane 23 hours/day for 11 days (Landry et al. 1987,1989), or in rats or dogs exposed to 9,980 ppm 

chloroethane 6 hours/day, 5 days/week for 2 weeks (Landry et al. 1982). Ophthalmoscopic examination of 

the eyes of the chloroethane-exposed dogs also did not reveal any effects. 

Body Weight Effects. No studies were located regarding body weight effects in humans following 

inhalation exposure to chloroethane. Body weight gain was not significantly affected by exposures to 

15,000 ppm chloroethane for 5 daily 6-hour exposures in rats or mice (Fedtke et al. 1994a); to 436 ppm 4 

hours/day for 8 of 10 days in rats (Schmidt et al. 1972); to 4,843 ppm 23 hours/day for 11 days in mice 

(Landry et al. 1987, 1989); to 9,980 ppm 6 hours/day, 5 days/week for 2 weeks, in rats or dogs (Landry et 

al.1982); or 19,000 ppm 6 hours/day, 5 days/week for 2 weeks, in rats or mice (NTP 1989). Exposure to 

4,946 ppm chloroethane 6 hours/day on gestation days 6-l 5 did not affect body weight gain of pregnant 

mice (Scortichini et al. 1986). 

Following longer duration exposures to chloroethane, body weight gain was not significantly affected in 

rats or mice by exposures to 19,000 ppm 6 hours/day, 5 days/week for 13 weeks, or 15,000 ppm 6 

hours/day, 5 days/week for approximately 2 years (NTP 1989). Body weight gain of 62 g less than 

controls was reported in rats exposed to 216 ppm chloroethane for 6 months (Troshina 1966). Because 

experimental methods were not described in detail, the Troshina (1966) study is not presented in Table 2-l 

or Figure 2-l. 

2.2.1.3 Immunological and Lymphoreticular Effects 

One study of immunological effects in humans exposed to chloroethane was found. Troshina (1966) 

compared the leukocyte phagocytic activity of 25 workers who may have been exposed to chloroethane 

vapors for 1.5-3 years with that of 25 control workers and found a significant decrease in phagocytic 

activity in the exposed workers. Levels of chloroethane in the plant were not reported. This study was not 

used as the source of a LOAEL value because it did not contain an adequate description of either methods 

or results. 

There were no reliable reports of immunological effects in animals after inhalation of chloroethane. 
CHLOROETHANE 39 

2. HEALTH EFFECTS 

Rat spleen and thymus weight were not affected by exposure to 436 ppm chloroethane for 4 hours/day for 

8 days (Schmidt et al. 1972). White blood cell counts were also unaffected in this study (Schmidt et al. 

1972). Histological changes in the thymus, spleen, and lymph nodes were not observed in mice exposed to 

4,843 ppm chloroethane 23 hours/day for 11 days (Landry et al. 1987,1989). There were no 

compoundrelated effects on organs or tissues of the immune system after exposure to 9,980 ppm 6 

hours/day, 5 days/week for 2 weeks, in rats or dogs (Landry et al. 1982), 19,000 ppm 6 hours/day, 5 

days/week for 2 weeks, in rats or mice (NTP 1989), 19,000 ppm 6 hours/day, 5 days/week for 13 weeks, in 

rats or mice (NTP 1989), or 15,000 ppm 6 hours/day, 5 days/week for approximately 2 years, in rats or 

mice (NTP 1989). 

Slightly congested or anemic spleens were observed in guinea pigs exposed to 40,000 ppm chloroethane 

for 90 minutes (Sayers et al. 1929). Reduced leukocyte phagocytic activity was reported in rats following 

both 60-day exposure to 5,305 ppm chloroethane and 6-month exposure to 2 16 ppm (Troshina 1966). 

These concentrations were not used as levels of significant exposure, however, because no experimental 

details were provided. 

The highest NOAEL values for immunological effects from each reliable study in each species and 

duration category are recorded in Table 2- 1 and plotted in Figure 2- 1. 

2.2.1.4 Neurological Effects 

There are numerous reports of neurological effects in humans exposed to chloroethane by inhalation. 

Marked dizziness was reported in volunteers who were given 3 breaths of 20,000 ppm chloroethane 

(Sayers et al. (1929). A subjective feeling of intoxication and decreased reaction times were reported in 

persons during exposure to 13,000 ppm for 12 minutes (Davidson 1925). At 19,000 ppm, slight 

intoxication was recorded within 1 minute of exposure. This effect progressed to distinct intoxication and 

mild analgesia within 12 minutes. At higher concentrations, more pronounced effects appeared, such as 

slight incoordination within 15 minutes at 25,000 ppm and marked incoordination within 8 minutes at 

33,600 ppm. Inhalation of 33,600 ppm chloroethane in oxygen produced unconsciousness in 13-17 

minutes (Davidson 1925). The number of subjects exposed at each concentration was not clearly stated in 

this study, and there was no discussion regarding how long it took for the subjects to recover fully from 

the effects of chloroethane. 
CHLQROETHANE 40 

2. HEALTH EFFECTS 

Chloroethane, combined with nitrous oxide and oxygen, was used to maintain anesthesia in patients 

previously made unconscious by administration of either thiopentone (thiopental), nitrous oxide, or a 

mixture of nitrous oxide, chloroethane, and oxygen (Cole 1956). A concentration of 20,000 ppm 

chloroethane was initially required to maintain anesthesia, but this could slowly be reduced to as low as 

5,000 ppm in some cases. Anesthesia could be maintained up to an hour using chloroethane in this 

manner. In a similar study using 36,000 ppm chloroethane, the length of time required to recover from 

anesthesia varied from 3 to 15 minutes in 33 subjects (Cole 1967). This result was not used as a level of 

significant exposure because chloroethane was administered in combination with other anesthetic agents. 

Unconsciousness is not the only neurological effect reported in humans following exposure to anesthetic 

concentrations of chloroethane. Anesthetic concentrations of chloroethane also produced vagus nerve 

stimulation leading to cardiac depression in subjects studied by Bush et al. (1952). A LOAEL was not 

taken from this study because the effective concentration of chloroethane was not reported. As indicated in 

Section 2.2.1.2, gastrointestinal effects (nausea, vomiting, mild abdominal cramps) have been reported in 

people recovering from chloroethane anesthesia (Cole 1967). Because these effects are thought to have a 

neurological basis, the NOAEL and LOAEL associated with the gastrointestinal effects in humans in the 

Davidson (1925) study are also presented in Table 2-l and plotted in Figure 2-l under neurological effects. 

A woman who inhaled chloroethane daily as a narcotic for 4 months had several signs and symptoms 

indicating cerebellar dysfunction. A neurological examination revealed ataxia, nystagmus (rapid eye 

movement), scanning dysarthria (imperfect speech articulation), dysdiadochokinesia (inability to perform 

alternating movements) of the arm, and sluggish lower limb reflexes (Hes et al. 1979). After 1 month 

without chloroethane, her neurological condition returned to normal. The woman had previously used 

other drugs but was reported to be free of addiction for 2 years before starting to use chloroethane (Hes et 

al. 1979). In a second case of chloroethane abuse, neurological signs and symptoms observed during the 

withdrawal period included a grand mal seizure, ataxia, difficulties in walking, disorientation, short-term 

memory impairment, and visual hallucinations (Nordin et al. 1988). Electroneurography indicated 

neuropathy of motor and sensory neurons (Nordin et al. 1988). Because it provided a euphoric effect, this 

male subject had abused chloroethane for about 30 years, and during the 4 months before he was admitted 

to the hospital, inhaled at least 100 ml/day. This subject also had a history of alcohol and sedative abuse, 

although no ethanol was in his breath on hospital admission. After approximately 6 weeks, the 

neurological and mental changes regressed without any residual symptoms. The study authors indicated 

that it was not possible to determine if the nervous system effects were toxic effects of chloroethane or 

withdrawal 
CHLOROETHANE 41 

2. HEALTH EFFECTS 

symptoms. Levels of significant exposure were not based on these reports because the effective 

concentration of chloroethane was not reported. 

Only one study of chloroethane exposure in an industrial setting was found. Seventy-six workers in a butyl 

rubber plant possibly exposed to chloroethane vapors for 2 months to 3 years were examined; 

approximately half had autonomic nervous system dysfunction in the form of intensified parasympathetic 

tonus (Troshina 1966). The study author indicated that autonomous nervous system function was 

measured with a battery of tests, including Ashner’s test, a synapse test, and a white spot test, but 

additional details were not provided. Concentrations of chloroethane in the plant were not reported. 

Neurological effects of chloroethane inhalation have also been studied in animals. Guinea pigs exposed to 

20,000 ppm chloroethane were unsteady, sluggish, and dizzy during a 9-hour exposure (Sayers et al. 

1929). Those exposed to 40,000 ppm were unsteady and dizzy after 3 minutes of exposure. At higher 

concentrations (>51,000 ppm), these effects were seen after shorter exposure durations, and more severe 

effects were found such as inability to stand, lying on the side, convulsions, and unconsciousness. Twohour inhalation of 54,948 ppm produced nervous excitation and convulsions followed by narcosis in mice 

and rats (Troshina 1966). Respiratory paralysis also occurred in some cases, leading to death. 

Histopathological examination revealed degeneration of nerve cells in the medulla oblongata and 

subcortical stratum of the brain (Troshina 1966). In dogs, concentrations of chloroethane that produced 

anesthesia also produced stimulation of the vagus nerve and, consequently, cardiac depression (Bush et al. 

1952). Premeditation with anticholinergic drugs inhibited vagal stimulation (Bush et al. 1952). Muscle 

twitching and tremors have also been observed in dogs during chloroethane anesthesia (Morris et al. 

1953). LOAELs were not taken from these studies because the effective concentrations of chloroethane 

were not reported. 

There were few reports of neurological effects in studies of longer duration. Brain histopathology and 

weight in the rat were unaffected by eight 4-hour exposures to 436 ppm chloroethane (Gohlke and 

Schmidt 1972; Schmidt et al. 1972). Slight lethargy was observed in rats, and hyperactivity was observed 

in 1 of 2 dogs exposed to 9,980 ppm chloroethane 6 hours/day, 5 days/week for 2 weeks (Landry et al. 

1982). Brain weight and brain or peripheral nerve histopathology were not affected. Evaluation of the dogs 

for gait, posture, cranial nerve reflexes, postural reactions, spinal cord reflexes, muscle tone, and pain 

perception also did not reveal any chloroethane-related effects (Landry et al. 1982). When mice received 

11 days of near-continuous exposure to 4,843 ppm chloroethane, no neurological effects were found by 

function testing or histopathological examination (Landry et al. 1987, 1989). No compound-related 

neurological effects were 
CHLOROETHANE 42 

2. HEALTH EFFECTS 

found in histopathological examinations of rats and mice exposed to 19,000 ppm chloroethane 6 

hours/day, 5 days/week for 2 or 13 weeks (NTP 1989). No increase in the occurrence of non-neoplastic 

lesions was found in nervous system organs or tissues following exposure of rats and mice to 15,000 ppm 

chloroethane 6 hours/day, 5 days/week for approximately 2 years (NTP 1989). This study did, however, 

report hyperactivity of female mice during the daily exposure period. A temporary increase in the 

threshold of electrodermal excitability occurred in rats after 60 days of exposure to 5,305 ppm, but not 

after 6 months of exposure to 216 ppm (Troshina 1966). 

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

each species and duration category are recorded in Table 2-l and plotted in Figure 2-l. The results of the 

study by Troshina (1966) were not used as levels of significant exposure because experimental methods 

and results were not described in sufficient detail. 

2.2.1.5 Reproductive Effects 

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

chloroethane. 

Several studies investigated reproductive endpoints in animals. In dogs anesthetized with chloroethane, 

high concentrations resulted in decreased uterine motility and muscle tonus (Van Liere et al. 1966). This 

study was not used as the basis for a LOAEL because the effective concentration of chloroethane was not 

reported. In addition, the relevance of this endpoint to other reproductive effects is unclear. No effects on 

uterine weights were observed in rats exposed to 15,000 ppm chloroethane 6 hours/day for 5 days (Fedtke 

et al. 1994a). Compared to unexposed controls, absolute and relative uterine weights were decreased by 

approximately 35% in mice exposed to 15,000 ppm chloroethane 6 hours/day for 5 days (Fedtke et al. 

1994a). Significant decreases in uterine glutathione levels were observed in both rats and mice (Fedtke et 

al. 1994b). The decreases in glutathione in the uterus were greater than the decreases in glutathione 

observed in the liver, lungs, and kidneys. A small increase in the average duration of the estrous cycle was 

observed in mice exposed to 15,000 ppm chloroethane 6 hours/day for 21 days (Bucher et al. 1995). 

Before the exposure, estrous cycle duration was 5.15±0.15 days, while during the exposure, estrous cycle 

duration was 5.52±0.19 days. Measurement of serum estradiol and progesterone did not reveal any 

consistent statistically significant changes attributable to chloroethane exposure. 
CHLOROETHANE 43 

2. HEALTH EFFECTS 

Testes weights were not affected in rats exposed to 436 ppm chloroethane 4 hours/day for 8 days during a 

l0-day time period (Schmidt et al. 1972). Sperm motility in rats was reduced after exposure to 

chloroethane for 6 months (Troshina 1966). At 22.7 ppm, the effect subsided after the exposure period 

ended, but at 216 ppm no recovery occurred during the month after exposure. Methods and results were 

inadequately reported in this study, so it was not used for a LOAEL. 

Histopathological changes in reproductive organs were not observed in mice exposed to 4,843 ppm 

chloroethane 23 hours/day for 11 days (Landry et al. 1987, 1989), or in rats and dogs exposed to 9,980 

ppm chloroethane 6 hours/day, 5 days/week for 2 weeks (Landry et al. 1982). Microscopic examination of 

the reproductive organs of 3 of 10 rats and 3 of 10 mice exposed to 19,000 ppm chloroethane 6 hours/day, 

5 days/week for 2 weeks, did not reveal any effects (NTP 1989). Because histopathological examinations 

were completed on only a few animals, this study is not presented in Table 2-l or Figure 2-l for 

reproductive effects. No compound-related histopathological changes were found in the reproductive 

organs of rats or mice exposed to 19,000 ppm chloroethane 6 hours/day, 5 days/week for 13 weeks, or to 

15,000 ppm 6 hours/day, 5 days/week for approximately 2 years (NTP 1989). 

No effects on the number of live and dead fetuses or on the number and position of resorption sites were 

observed in mice exposed to 4,946 ppm chloroethane 6 hours/day on gestation days 6-15 (Scortichini et al. 

1986). Additional studies of reproductive outcome in animals following inhalation exposure to 

chloroethane were not identified. 

The highest NOAEL values and all LOAEL values from each reliable study for reproductive effects in 

each species and duration category are recorded in Table 2-l and plotted in Figure 2-l. 

2.2.1.6 Developmental Effects 

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

chloroethane. 

Only one study of the developmental effects of chloroethane in animals was found. In mice, 6-hour 

inhalation exposure to 4,946 ppm chloroethane on gestation days 6-15 resulted in minimal evidence of 

fetotoxicity (Scortichini et al. 1986). A small, statistically significant (p=0.05) increase in the incidence of 

foramina of the skull bones (small centers of unossified bone) was observed. This effect was observed in 

5,4,4, and 
CHLOROETHANE 44 

2. HEALTH EFFECTS 

23% of the litters at 0, 491, 1,504, and 4,946 ppm, respectively. An increase in supernumerary ribs was 

also found, although this effect was not indicated as statistically significant. The incidences of litters with 

supernumerary ribs were 9,4, 19, and 18% at 0, 491, 1,504, and 4,946 ppm, respectively. No effects were 

observed on maternal body or liver weights, reproductive parameters, fetal body weight, or the incidence 

of external or visceral malformations in the fetuses The NOAEL and LOAEL for fetotoxic effects in mice 

are recorded in Table 2-l and plotted in Figure 2-l 0 Based on the NOAEL of 1,504 ppm for developmental 

effects in mice (Scortichini et al. 1986), an acute-duration inhalation MRL of 15 ppm was calculated, as 

described in the footnote to Table 2-1. 

2.2.1.7 Genotoxic Effects 

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

chloroethane. 

Chloroethane did not increase the number of micronuclei in bone marrow cells or affect DNA synthesis in 

mice exposed nose-only to 25,000 ppm chloroethane 6 hours/day for 3 days (Ebert et al. 1994). The 

investigators indicated that the exposure concentration used in this study was about 66% of the 

flammability limit and that it was the highest concentration that could be safely administered. 

Other genotoxicity studies are discussed in Section 2.5. 

2.2.1.8 Cancer 

No studies were located regarding cancer in humans following inhalation exposure to chloroethane. 

A study of the carcinogenicity of chloroethane vapor in animals has been completed. Inhalation exposure 

to 15,000 ppm chloroethane 6 hours/day, 5 days/week for 102 weeks, produced evidence of 

carcinogenicity in both male and female rats (NTP 1989). The combined incidence of skin 

trichoepitheliomas, sebaceous gland adenomas, and basal cell carcinomas was 10% (5/50) in treated male 

rats and 0% (0/50) in concurrent controls. This increase was statistically significant when compared to the 

mean historical inhalation control incidence of 0.7% (n=300) and the historical untreated control incidence 

of 2% (n=1,936). It is reasonable to combine incidence data of these neoplasms because they are 

morphologically similar (all are epithelial tumors arising from the epidermis or associated structures). 

Malignant brain astrocytomas were found in 6% (3/50) of the treated female rats and 0% (0/50) of the 

concurrent controls. This increase was statistically significant 
CHLOROETHANE 45 

2. HEALTH EFFECTS 

compared to the historical inhalation control incidence of 0.3% (n=297) and the historical untreated glial 

cell tumor incidence of 1.2% (n=l,969). All three affected rats died before the end of the study and it was 

suggested that the brain tumors may have been the cause of death. The NTP (1989) concluded that this 

study provides equivocal evidence of the carcinogenicity of chloroethane in both male and female rats. A 

CEL of 15,000 ppm for rats is reported in Table 2-1 and plotted in Figure 2-l. 

There was a highly significant increase in the incidence of uterine carcinomas of endometrial origin in 

female mice exposed to 15,000 ppm chloroethane 6 hours/day, 5 days/week for 100 weeks (NTP 1989). 

These tumors, which were highly malignant and metastasized to a wide variety of organs, were found in 

86% (43/50) of treated females and 0% (0/49) of concurrent controls. In addition, there was a significant 

increase in hepatocellular carcinomas, which occurred in treated female mice at an incidence of 15% 

(7/48) and concurrent controls at 6% (3/49). A significant increase in the occurrence of lymphomas in 

treated female mice was discounted because concurrent control values were abnormally low compared to 

historical control values. In males, the combined incidence of alveolar and bronchiolar adenomas was 17% 

(8/48), a significant increase compared to the 6% (3/50) incidence in concurrent controls. The combined 

incidence of adenomas and carcinomas was 21% (10/48) in exposed mice and 10% (5/50) in concurrent 

controls. The study authors concluded that this study provides clear evidence of the carcinogenicity of 

chloroethane in female mice but that the study was inadequate for male mice because of low survival. A 

CEL of 15,000 ppm for mice is reported in Table 2- 1 and plotted in Figure 2- 1. 

2.2.2 Oral Exposure 

No studies were located regarding the following effects in humans or animals after oral exposure to 

chloroethane. 

2.2.2.1 Death 

2.2.2.2 Systemic Effects 

2.2.2.3 Immunological and Lymphoreticular Effects 

2.2.2.4 Neurological Effects 
CHLOROETHANE 46 

2. HEALTH EFFECTS 

2.2.2.5 Reproductive Effects 

2.2.2.6 Developmental Effects 

2.2.2.7 Genotoxic Effects 

Genotoxicity studies are discussed in Section 2.5. 

2.2.2.6 Cancer 

No studies were located regarding cancer in humans or animals after oral exposure to chloroethane. 

2.2.3 Dermal Exposure 

2.2.3.1 Death 

No studies were located regarding death in humans or animals following dermal exposure to chloroethane. 

2.2.3.2 Systemic Effects 

No studies were located regarding respiratory, cardiovascular, gastrointestinal, hematological, hepatic, 

renal, or ocular effects in humans or animals following dermal exposure to chloroethane. 

Musculoskeletal Effects. No studies were located regarding musculoskeletal effects in humans 

following dermal exposure to chloroethane. 

One study investigated the musculoskeletal effects of dermally applied chloroethane in animals. 

Chloroethane sprayed onto a l-2-cm2

 area on the thighs of rats until the skin was blanched produced local 

infiltration and disintegration of muscle fibers (Kenig 1956). This study, available only as an abstract, was 

not used as the basis for a LOAEL because the effective dose of chloroethane was not reported and few 

experimental details were provided. 
CHLOROETHANE 47 

2. HEALTH EFFECTS 

Dermal Effects. Dermally applied chloroethane is used as a local anesthetic in humans (Nielsen 

1980; Noble 1979; Ott 1969; Van Ketel 1976). When sprayed on the skin, chloroethane rapidly evaporates 

and causes the skin to freeze, which produces a numbing sensation. It is used for procedures such as skin 

biopsy and ear piercing that require short periods of surface anesthesia in a small area (Ott 1969). It is also 

used topically to relieve pain in facial muscles during physical therapy for those suffering from 

temperomandibular pain and dysfunction syndrome (also known as temperomandibular joint syndrome, or 

TMJ) (Marbach 1996). When used as a topical anesthetic, chloroethane is usually applied for 30 seconds 

or less. Symptoms of frostbite can result from prolonged exposures. Three children who had their earlobes 

sprayed with chloroethane for several minutes all developed chemical frostbite on their ears and necks 

(Noble 1979). This report was not used as the basis for a LOAEL because the effective dose of 

chloroethane was not reported. As discussed in Section 2.2.3.3, humans can develop dermal contact 

sensitivity reactions to chloroethane (Bircher et al. 1994; Kriechbaumer et al. 1998; Van Ketel 1976). 

Dermal effects have also been reported in animals Chloroethane has the same topical anesthetic qualities 

in animals as it does in humans (Dobkin and Byles 1971). Chloroethane applied to a l-2-cm2

 area on the 

thighs of rats until the skin was blanched produced edema in the subcutaneous tissue of the application site 

(Kenig 1956). This study, available only as an abstract, was not used as the basis for a LOAEL because the 

effective dose of chloroethane was not reported and few experimental details were provided. 

2.2.3.3 Immunological and Lymphoreticular Effects 

Dermal exposure to chloroethane can result in contact sensitivity. Patch tests performed on two patients 

with eczema were strongly positive for chloroethane, while a third patient suffered an eczematous reaction 

after the use of chloroethane as a local anesthetic, indicating that allergy to chloroethane can occur. Patch 

tests on 15 control volunteers were negative (Van Ketel 1976). A punch biopsy taken from a woman with 

a positive patch test to chloroethane revealed observations consistent with a T-cell-mediated allergic 

reaction (Bircher et al. 1994). Microscopic examination showed marked spongiosis and a 

lymphohistocytic infiltrate. There was a marked dermal infiltrate of CD3+

 T cells (pan T cells), with a 

predominance of CD4+ T cells (helper/suppressor cell subtypes). Most of the cells expressed lymphocyte 

function-associated antigen. A considerable number of CDl+

 Langerhans cells were also found in the 

epidermis. 

No studies were located regarding immunological and lymphoreticular effects in animals following dermal 

exposure to chloroethane. 
CHLOROETHANE 48 

2. HEALTH EFFECTS 

2.2.3.4 Neurological Effects 

Mild pain was reported when chloroethane was sprayed on a small area of 1 hand each of 40 women 

(Selby and Bowles 1995). The chloroethane was sprayed for 10 seconds, from a height of 20 cm. This 

procedure was used as analgesia for venous cannulation, a procedure that was reported to be more painful 

without pretreatment with chloroethane. 

There is one study of the neurological effects of dermally applied chloroethane in animals. Rats were 

sprayed with chloroethane until their skin was blanched, and examination of the nerve fibers at the site of 

application (a 1-2-cm2

 area of the thigh) revealed thickening of the fibers and swelling of the Schwann cell 

nuclei (Kenig 1956). These effects subsided within 10 days of application. This study, available only as an 

abstract, was not used as the basis for a LOAEL because the effective dose of chloroethane was not 

reported and few experimental details were provided. 

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

to chloroethane. 

2.2.3.5 Reproductive Effects 

2.2.3.6 Developmental Effects 

2.2.3.7 Genotoxic Effects 

Genotoxicity studies are discussed in Section 2.5. 

2.2.3.8 Cancer 

No studies were located regarding cancer in humans or animals after dermal exposure to chloroethane. 

2 . 3 TOXICOKINETICS 

Chloroethane is readily absorbed following inhalation exposure. Data regarding the absorption of 

chloroethane following oral exposure were not identified. Based on physical properties, a dermal flux rate of 
CHLOROETHANE 49 

2. HEALTH EFFECTS 

0.99 mg/cm2 hour has been estimated. Partition coefficients indicate that chloroethane, once absorbed, 

would have a greater affinity for fat than for muscle or the liver. 

The metabolism of chloroethane has not been studied in humans. In rats and mice, the two major pathways 

of chloroethane metabolism are the production of acetaldehyde by cytochrome P450, and conjugation of 

chloroethane with glutathione to form S-ethyl-glutathione. Acetaldehyde is rapidly metabolized to acetic 

acid. The glutathione metabohtes are further metabolized to S-ethyl-L-cysteine in mice, and S-ethyl-Nacetyl-L-cysteine in both rats and mice. Glutathione conjugate metabolites of chloroethane are excreted in 

the urine, while unmetabolized chloroethane is exhaled. 

2.3.1 Absorption 

2.3.1.1 Inhalation Exposure 

Chloroethane is readily absorbed through the lungs in humans and animals (Konietzko 1984; Lehman and 

Flury 1943; Torkelson and Rowe 1981). The rapidity of anesthesia in humans and animals following 

inhalation exposure supports this contention (Dobkin and B yles 197 1; Finer 1966; Lawson 1965). Human 

subjects were exposed to about 5 mg 38Cl-labeled chloroethane for 30 seconds by taking 1 breath through 

the mouth and then holding it for 30 seconds (Morgan et al. 1970). Approximately 18% of the 

radioactivity was exhaled in the first 2 breaths indicating that about 82% was retained. 

No data are available to indicate that absorption of chloroethane would be different in children as 

compared to adults. Exposure to chloroethane is most likely via inhalation. Since infants and adolescents 

breathe more air per kilogram than adults, it is possible that children could inhale more chloroethane 

relative to their body weight than adults. However, infants have less developed alveoli than adults, which 

may result in a smaller surface area for absorption (NRC 1993). 

2.3.1.2 Oral Exposure 

No studies were located regarding absorption in humans or animals following oral exposure to 

chloroethane. 
CHLOROETHANE 50 

2. HEALTH EFFECTS 

2.3.1.3 Dermal Exposure 

A dermal flux rate of 0.99 mg/cm2/hour was estimated based on the physical properties of chloroethane 

(Fiserova-Bergerova et al. 1990). Based on physical properties, the study authors considered chloroethane 

to have no significant dermal absorption potential. No quantitative studies were located regarding 

absorption in humans or animals following dermal exposure to chloroethane. 

2.3.2 Distribution 

Partition coefficients for human blood and serum measured in vitro at 40 °C were 1.9 for blood/air and 1.2 

for serum/air (Morgan et al. 1970). A blood/air partition coefficient for humans of 2.69±0.2 has also been 

determined in vitro at 37°C (Gargas et al. 1989). Rat tissue/air partition coefficients of 38.6±0.7, 

4.08±0.39, 3.61±0.32, and 3.22±0.68 for fat, blood, liver, and muscle, respectively, suggest that 

chloroethane has a higher affinity for fat than for blood, liver, or muscle (Gargas et al. 1989). These 

partition coefficients were determined in vitro at 37 °C using tissues from F344 rats. 

No concrete data are available to indicate that distribution of chloroethane is different in children. 

Physical-chemical properties of chloroethane indicate that it would be readily soluble in fat. In the 

newborn and young infant, fat tissue is relatively scarce (15% of body weight; Morselli et al. 1980) as 

compared to an adult, indicating that distribution of lipophilic chloroethane will differ in infants and young 

children relative to adults. In addition, infants and younger children have much more total body and 

extracellular water relative to body weight than adults (Altman and Dittmer 1974), indicating that 

distribution of water-soluble compounds, such as chloroethane metabolites, will differ in children as 

compared with adults (Morselli et a1.1980). 

The brain of a child is much larger, relative to body weight, than in the adult (Guzelian et al. 1992). 

Further, cerebral blood flow is greater, relative to brain weight, in the child than in the adult (Guzelian et 

al. 1992). Therefore, chloroethane present in the blood after exposures (such as inhalation) will more 

readily reach the brain of a child due to this increased blood flow. Since the central nervous system is the 

target organ for chloroethane’s narcotic effects, the larger relative brain size of the child indicates that a 

child might experience a much larger exposure dose relative to body weight than an adult. 
CHLOROETHANE 51 

2. HEALTH EFFECTS 

It is unknown if chloroethane can reach and cross the placenta or its precursors. However, based on 

physical-chemical characteristics of the compound, it is likely that it can. In addition, it is known that 

some chloroethane metabolites such as ethanol (Guzelian et al. 1992), can cross the placental barrier. 

One study to date (Pellizari et al. 1982) determined that chloroethane does enter the milk of a lactating 

woman and can be detected. However, this study did not qluantify the chloroethane in milk, few women 

were tested, and the route of exposure to chloroethane was not determined. Therefore, it is impossible to 

estimate what percentage of exposed nursing mothers would be expected to excrete the compound in milk 

and what the significance of the compound in mother’s milk would be for a nursing infant. 

No data are available to indicate that females store chloroethane or its metabolites in their tissues. Data 

indicate that chloroethane is rapidly cleared within the body; therefore, it is unlikely that any of the 

compoundwould be stored in tissues, and it would not likely be available to be mobilized at a later time 

during pregnancy or lactation. 

No data are available concerning the possibility of chloroethane entering into and adversely affecting 

parental germ cells. 

2.3.2.1 Inhalation Exposure 

No studies were located regarding distribution in humans or animals following inhalation exposure to 

chloroethane. Reviews of the effects of chloroethane (Konietzko 1984; Lehman and Flury 1943) provide 

some general information about the distribution of chloroethane. The species in which the information was 

obtained was not stated. In the blood, approximately 75% of the chloroethane is bound to red blood cells, 

and 25% is in the plasma (Konietzko 1984). The highest concentration of chloroethane in the animal body 

was found in fatty tissue around the kidney, and the lowest was found in the cerebrospinal fluid 

(Konietzko 1984). The brain was said to accumulate a concentration two times that of the blood. Lehman 

and Flury (1943) reported that chloroethane content in the brain and medulla oblongata was especially 

high. 

2.3.2.2 Oral Exposure 

No studies were located regarding distribution of chloroethane in humans or animals following oral 

exposure. 
CHLOROETHANE 52 

2. HEALTH EFFECTS 

2.3.2.3 Dermal Exposure 

No studies were located regarding distribution of chloroethane in humans or animals following dermal 

exposure. 

2.3.3 Metabolism 

No studies were located regarding metabolism of chloroethane by humans. A review indicates that a small 

amount of chloroethane was metabolized to ethanol via dechlorination in animals following administration 

of high anesthetic doses (Konietzko 1984). The species was not identified. 

Less than 0.5% of the dose was dechlorinated by rat liver microsomes in vitro (Van Dyke and Wineman 

1971). 

The metabolic rates for chloroethane were estimated for male F344 rats using a gas uptake method 

(Gargas et al. 1990). The rats were exposed to an initial concentration of 100, 535, 1,200, or 2,350 ppm, 

and the disappearance of the gas was studied for about 5 hours. A physiologically based pharmacokinetic 

(PBPK) model that assumed metabolism occurred exclusively in the liver was used to analyze the data. 

The metabolism of chloroethane was best described by a combination of a saturable pathway and a firstorder pathway. The Vmaxc which is the maximum velocity (Vmax) scaled for a 1-kg animal, was determined 

to be 4 mg/hour (to calculate a Vmax for an animal of any body weight [body weight in kg] use Vmax = 

Vmaxc[BW]0.7). The rate constant for the saturable pathway (Km was estimated to be 0.1 mgL. The firstorder rate constant, kfc which is the rate constant (Kf scaled for a l-kg animal, was 1 hr-1 (to calculate a kf 

for any body weight use kf = kfc[BW]-0.3). 

The proposed metabolic pathways for chloroethane in rats and mice (Fedtke et al. 1994b) are shown in 

Figure 2-2. The two major pathways are the production of acetaldehyde by cytochrome P450, and 

conjugation of chloroethane with glutathione to form S-ethyl-glutathione. The metabolism of chloroethane 

to acetaldehyde was studied in vitro using livers from rats and mice exposed to chloroethane at 0 or 15,000 

ppm 6 hours/day for 5 days (Fedtke et al. 1994a). The amounts of acetaldehyde detected ranged from 26.9 

to 49.3% of the chloroethane metabolized, depending on pre-exposure to chloroethane, for the individual 

microsome preparations from rats and mice. The investigators found that exposure to chloroethane 

induced its own metabolism by approximately 100% in mice and female rats, with no effect in male rats. 

Based on 
CHLOROETHANE 53 

2. HEALTH EFFECTS 

studies using specific P450 enzyme inducers and inhibitors, the investigators concluded that the P450 

enzyme DE1 (CYP2El) was responsible for chloroethane metabolism. CYP2E1 also metabolizes alcohols, 

aldehydes, and ketones, and plays a role in gluconeogenesis within the body (Vieira et al. 1996). 

Acetaldehyde is rapidly metabolized to acetic acid by aldehyde dehydrogenase. Therefore, increased 

acetaldehyde relative to normal levels was not detected in the serum of chloroethane-exposed rats or mice 

(15,000 ppm), or in the urine of exposed rats (Fedtke et al. 1994a). Small increases in acetaldehyde were 

detected in the urine of chloroethane-exposed mice. Acetaldehyde concentrations in the urine of male and 

female mice were 7.9-20.3 and 0-l 8.1 μmol/L, respectively, in unexposed mice, and 15.4-70.1 and 11.6­

17 μmol/L, respectively, in chloroethane-exposed mice. Except for the approximately threefold greater 

metabolism of chloroethane in mice compared to rats, there was little difference between the species. The 

study authors concluded that the production of acetaldehyde from chloroethane was unlikely to have a role 

in the induction of uterine carcinomas in mice. 

Glutathione levels were studied in rats and mice exposed to chloroethane at 0 or 15,000 ppm 6 hours/day 

for 5 days (Fedtke et al. 1994b). The animals were sacrificed immediately after the last exposure. 

Compared to controls, glutathione concentrations were significantly (p<0.05) decreased in the livers of 

male rats, in the kidneys of female rats, in the lungs of both sexes of rats and mice, and in the uteri of both 

rats and mice. The decreases in glutathione levels were most dramatic in the uterus, in which levels were 

approximately two-thirds lower than in controls. In vitro studies of chloroethane conjugation to 

glutathione, using liver cytosolic fractions from control and chloroethane-exposed rats and mice, indicated 

that the conjugation was catalyzed by glutathione-S-transferase enzymes (Fedtke et al. 1994b). 

Glutathione conjugation rates, in nmol chloroethane conjugated/minute mg protein, were greater in mice 

(0.71±0.19 in males; 1.01±0.19 in females) than in rats (0.17±0.19 in males; 0.16±0.03 in females). 

Chloroethane exposure had no effect on these rates in rats and slightly decreased the rates in mice. When 

urine was analyzed for glutathione metabolites, S-ethyl-N-acety-L-cysteine was detected in both rats and 

mice. S-Ethyl-L-cysteine was detected only in the urine of mice. The total amount of glutathione 

metabolites excreted during the 5-day exposure period was about fivefold higher in mice than in rats. The 

study authors concluded that rats completely metabolize S-ethyl-L-cysteine to more hydrophilic 

metabolites before urinary excretion, while these metabolic pathways were not available to the same extent 

in mice under the conditions of this study. 

No data are currently available to indicate that the metabolism of chloroethane is different in children 

when compared to adults; however, some of the enzymes in the chloroethane metabolism scheme 

belong to enzyme 

CHLOROETHANE 55 

2. HEALTH EFFECTS 

families that are developmentally regulated to some extent either in humans or animals. Chloroethane is 

metabolized by both cytochrome P450 and by glutathione S-transferase. Studies have shown that liver 

glutathione S-transferase activities are low in prepubertal male and female rats, but as the rats reach sexual 

maturity (at around 30-50 days of age), glutathione-conjugating activity toward dichloronitrobenzene is 

two to threefold higher in males than females (Lamartiniere and Lucier 1983). The difference in 

glutathione S-transferase activity was dependent on pituitary secretions. Further research on 

hypophysectomized male and female rats revealed that growth hormones may contribute to the 

establishment of glutathione S-transferase activities (Lamartiniere 1981). No data are available to indicate 

that glutathione S-transferase activity is developmentally or sexually expressed in humans. 

After glutathione conjugation of chloroethane, three other enzymes convert the conjugate to a more 

hydrophilic form to be excreted by the body. These enzymes are γ-glutamyltranspeptidase, cysteinyl 

glycinase, and N-acetyltransferase, NAT (Amdur et al. 1991). These three enzymes convert elatively 

hydrophobic glutathione conjugates to their respective mercapturic acids, which can be excreted more 

readily. There are two N-acetyltransferase enzyme families, NAT1 and NAT2. Of these enzymes, only 

NAT2 is developmentally regulated. It is unknown which NAT enzyme metabolizes chloroethane; 

therefore, it is unknown whether chloroethane is developmentally regulated by this metabolic pathway. 

Studies have shown that the other enzyme metabolizing chloroethane, cytochrome P45OIIEl (CYP2El), is 

developmentally regulated in humans (Vieira et al. 1996). This enzyme is not detectable from livers of 

fetuses at 14-40 gestational weeks. However, the level of the protein rises sharply in the first day after 

birth ( 1 unit/mg protein) and continues to increase until it reaches adult values in children from 1 to 10 

years of age, approximately 5 units/mg protein (Vieira et al. 1996). 

2.3.4 Elimination and Excretion 

2.3.4.1 Inhalation Exposure 

Excretion of chloroethane by the lungs is rapid in humans and animals (Adriani 1986; Konietzko 1984; 

Lehman and Flury 1943; Torkelson and Rowe 1981). In humans exposed briefly by inhalation to 

chloroethane, 30% of the retained dose was excreted in the breath within 1 hour (Morgan et al. 1970). 

Excretion over a longer period of time could not be measured because of the short half-life of the 38Cl 
CHLOROETHANE 56 

2. HEALTH EFFECTS 

radioisotope used in this study. Morgan et al. (1970) found that the rate of excretion of radioactivity in the 

urine of humans was very slow (i.e., <0.01% per minute) I hour after inhalation. 

Small increases in acetaldehyde were detected in the urine of chloroethane-exposed mice but not rats 

(Fedtke et al. 1994a). Acetaldehyde concentrations in the urine of male and female mice were 7.9-20.3 and 

0-l 8.1 μmol/L, respectively, in unexposed mice, and 15.4-70.1 and 11.6-17 μmol/L,respectively, in 

chloroethane-exposed mice. Acetaldehyde is rapidly metabolized to acetic acid; therefore it would be 

difficult to detect in whole animal studies. Glutathione conjugates have also been detected in the urine of 

rats and mice exposed to chloroethane (Fedtke et al. 1994b). Rats excreted the more hydrophilic S-ethylN-acetyl-L-cysteine, while mice excreted both S-ethyl-N-acetyl-L-cysteine and S-ethyl-L-cysteine. During 

the 5 days that rats and mice were exposed to chloroethane at 15,000 ppm for 6 hours/day, the total 

amount of glutathione metabolites excreted in the urine was about fivefold higher in mice than in rats. 

2.3.4.2 Oral Exposure 

No studies were located regarding excretion of chloroethane and metabolites in humans or animals 

following oral exposure. 

2.3.4.3 Dermal Exposure 

No studies were located regarding excretion of chloroethane and metabolites in humans or animals 

following dermal exposure. 

No data are available to indicate that excretion of chloroethane is different in children, 

2.3.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic 

(PD) Models 

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

disposition of chemical substances to quantitatively describe the relationships among critical biological 

processes (Krishnan et al. 1994). PBPK models are also called biologically based tissue dosimetry models. 

PBPK models are increasingly used in risk assessments, primarily to predict the concentration of 

potentially toxic moieties of a chemical that will be delivered to any given target tissue following various 

combinations of route, dose level, and test species (Clewell and Andersen 1985). Physiologically based 

pharmacodynamic 
CHLOROETHANE 57 

2. HEALTH EFFECTS 

(PBPD) models use mathematical descriptions of the dose-response function to quantitatively describe the 

relationship between target tissue dose and toxic end points. 

PBPK/PD models refine our understanding of complex quantitative dose behaviors by helping to delineate 

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

of the toxic moiety, and (2) the target tissue dose and observed responses (Andersen et al. 1987; Andersen 

and Krishnan 1994). These models are biologically and mechanistically based and can be used to 

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

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

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

uncertainty factors. 

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

representation, (2) model parametrization, (3) model simulation, and (4) model validation (Krishnan and 

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

toxicologically important chemical substances, both volatile and nonvolatile (Krishnan and Andersen 

1994; Leung 1993). PBPK models for a particular substance require estimates of the chemical substancespecific physicochemical parameters, and species-specific physiological and biological parameters. The 

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

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

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

solutions. 

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

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

described, however, this simplification is desirable because data are often unavailable for many biological 

processes. A simplified scheme reduces the magnitude of cumulative uncertainty. The adequacy of the 

model is, therefore, of great importance, and model validation is essential to the use of PBPK models in 

risk assessment. 

PBPK models improve the pharmacokinetic extrapolations used in risk assessments that identify the 

maximal (i.e., the safe) levels for human exposure to chemical substances (Andersen and Krishnan 1994). 

PBPK models provide a scientifically-sound means to predict the target tissue dose of chemicals in 

humans who are exposed to environmental levels (for example, levels that might occur at hazardous waste 

sites) based on the results of studies where doses were higher or were administered in different species. 

Figure 2-3 shows a conceptualized representation of a PBPK model. 

CHLOROETHANE 59 

2. HEALTH EFFECTS 

If PBPK models for chloroethane exist, the overall results and individual models are discussed in this 

section in terms of their use in risk assessment, tissue dosimetry, and dose, route, and species 

extrapolations. 

See Section 2.3.3 for discussion of a study that used a PBPK model to estimate the metabolic parameters 

for chloroethane in rats (Gargas et al. 1990). This study was not used for risk assessment, tissue dosimetry, 

or dose, route, or species extrapolation. Therefore, it is not discussed in this section. 

There are no PBPK models for children, fetuses, pregnant women, infants or lactating women, or any 

other appropriate age group with which to make predictions concerning the pharmacokinetics of 

chloroethane in humans. In addition, these models are lacking in animals. 

2.4 MECHANISMS OF ACTION 

The exact mechanism of action for chloroethane toxicity has not been defined. It is generally accepted 

that chloroethane’s ability to target the central nervous system and the heart is based on its 

physicalchemical characteristics and similarity to other volatile halogenated organics with anesthetic 

properties. These currently accepted beliefs do not suggest that differences exist between children and 

adults in regards to the mechanism of toxicity of chloroethane. 

2.4.1 Pharmacokinetic Mechanisms 

Because chloroethane is a small lipophilic compound, simple diffusion accounts for its absorption across 

membranes, and its higher affinity for lipids determines its distribution. A review regarding the kinetics of 

chloroethane indicates that 75% of the compound in blood is bound to red blood cells, and 25% is in 

plasma (Konietzko 1984). This is consistent with the lipophilic nature of chloroethane. The metabolism of 

chloroethane has been studied in vitro using liver microsomal preparations from rats and mice (Fedtke et 

al. 1994a). The observations that inhibitors of the P450 enzyme IlEI reduce chloroethane metabolism, and 

that inducers of P450 IIEI enhance metabolism of the compound to acetaldehyde, provide evidence that 

P450 IIEI is the principal P450 enzyme involved in the metabolism of chloroethane. In vitro studies using 

hepatic cytosolic fractions from the livers of rats and mice have shown that the conjugation of 

chloroethane with glutathione is catalyzed by glutathione -S-transferase enzymes (Fedtke et al. 1994b). In 

mice, both S-ethyl-N-acetyl-L-cysteine and S-ethyl-L-cysteine are formed and excreted in the urine, while 

in rats, only S-ethyl-N-acetyl-L-cysteine is formed and excreted in the urine. 
CHLOROETHANE 60 

2. HEALTH EFFECTS 

2.4.2 Mechanisms of Toxicity 

Chloroethane has a general anesthetic effect when inhaled at high concentrations by humans and animals. 

The anesthetic effect is thought to be produced by the compound itself. Although the specific mechanism 

of action is unknown, it is generally believed that chloroetbane’s ability to induce anesthesia is related to 

the solubility of the compound in oils or fats. The lipophilicity of the nonpolar compound suggests that 

chloroethane is dissolved within and acts upon the lipid layer of cellular membrane or the hydrophobic 

areas of specific membrane-bound cellular proteins (Goodman and Gilman 1993). This hypothesis is 

supported by the findings of Balasubramanian and Wetlaufer (1966) who showed that chloroethane and 

other volatile anesthetics produced reversible structural changes in globular proteins in vitro. They 

proposed that the anesthetic activity of these compounds may be a result of their ability to produce 

structural changes in protein or lipoprotein structures. 

Volatile anesthetics affect voltage-gated calcium channels (Langmoen et al. 1995). Using a guinea pig 

heartlung preparation, Doring (1975) found that volatile general anesthetics including chloroethane 

interfere with the calcium-mediated process of excitation-contraction coupling leading to a reduction in 

high energy phosphate (ATP) utilization. Extra calcium, cardiac glycosides, or β-adrenergic 

catecholamines did not reverse the effects. Doring (1975) indicated that, because of their lipophilic nature, 

volatile anesthetics may alter the lipid arrangement of the transverse tubule walls, resulting in permanent 

impairment of excitationcontraction coupling. In studies using chloroform, Doring (1975) was able to 

show ultrastructural changes in the transverse tubules, especially vacuolization and dilatation Electron 

microscopic examinations of hearts similarly exposed to chloroethane were not presented, but 

chloroethane would be expected to act in a manner similar to chloroform. 

Chloroethane has been shown to have cardiotoxic effects in several studies (Bush et al. 1952; Cole 1967; 

Haid et al. 1954; Morris et al. 1953). At levels adequate to induce anesthesia, chloroethane sensitizes the 

heart to the effects of catecholamines (Haid et al. 1954; Morris et al. 1953). Catecholamine release can be 

induced by euphoria and excitement resulting from the effects of chloroethane on the central nervous 

system (Benowitz 1992). The myocardium can be sensitized to the effects of the catecholamines. This 

sensitization, along with asphyxia and hypoxia, which can also result from high concentrations of inhaled 

chloroethane, can cause arrhythmias, which can result in death (Benowitz 1992). It is possible that 

chloroethane and similar solvents may depress atrioventricular nodal conduction, causing atrioventricular 

block. Bradyarrhythmias 
CHLOROETHANE 61 

2. HEALTH EFFECTS 

(abnormally slow hearth rhythms) may then occur to prevent ventricular arrhythmias, or asystole (lack of 

electrical or mechanical activity in the heart) may result. 

Analysis of structure-activity relationships predicts that chloroethane is carcinogenic. The alerting 

substructure is the Cl-CH2 group, which results in chloroethane being an alkylating agent and a mutagen to 

Salmonella (Tennant and Ashby 1991). It is not known why chloroethane does not cause respiratory 

cancers following inhalation exposure, or why it acts as a selective carcinogen resulting in uterine tumors 

in mice. Based on a lack of differences in P450 metabolism of chloroethane between rats and mice, 

decreased uterine glutathione levels in rats and mice following chloroethane exposure, and the urinary 

excretion of S-ethyl-Lcysteine in mice but not rats, Fedtke et al. (1994b) suggested that uterine tumor 

production is a result of the glutathione conjugation pathway, rather than a result of chloroethane 

metabolism by P450 enzymes. The study authors did not state which compound in the glutathione 

conjugation pathway was responsible for the carcinogenic effect of chloroethane. 

2.4.3 Animal-to-Human Extrapolations 

The metabolism of chloroethane has not been studied in humans. Therefore, it is not possible to determine 

which species of animal is the most appropriate model for humans exposed to chloroethane. Studies by 

Fedtke et al. (1994a, 1994b) indicate that compared to rats, mice have a greater capacity to metabolize 

chloroethane by both the P450 and glutathione conjugation pathways. 

2.5 RELEVANCE TO PUBLIC HEALTH 

Issues relevant to children are explicitly discussed in 2.6 Children’s Susceptibility and 5.6 Exposures of 

Children. 

Overview 

Although chloroethane has been used as a general anesthetic in humans, very little is known about the 

effects of inhalation exposure to lower concentrations. The concentrations required to produce anesthesia, 

approximately 40,000 ppm, are near the explosion limit of this compound. Chloroethane is also used as a 

local anesthetic in humans. When chloroethane is sprayed on the skin, it rapidly evaporates and causes the 

skin to freeze, producing a numbing sensation. Oral exposure of humans to chloroethane has not been 
CHLOROETHANE 62 

2. HEALTH EFFECTS 

studied. Because chloroethane is a gas, substantial oral exposure of humans to this compound is not 

expected. 

Animal studies regarding the effects of chloroethane are predominantly focused on the inhalation route of 

exposure. At high concentrations for short periods of time, chloroethane clearly results in neurological 

effects producing unsteadiness followed by unconsciousness. A number of toxicity studies have not clearly 

identified a target organ of toxicity for chloroethane (Eandry et al. 1982, 1987,1989; NTP 1989). 

One target of chloroethane toxicity in animals exposed to high concentrations is the uterus. Chloroethane 

has been shown to decrease uterine weight by 35% in mice exposed to 15,000 ppm chloroethane 6 

hours/day for 5 days (Fedtke et al. 1994a). Significant decreases in uterine glutathione levels were also 

observed in both rats and r-nice (Fedtke et al. 1994b). Chloroethane has also been shown to produce 

uterine cancer in mice but not rats exposed to 15,000 ppm chloroethane for approximately 2 years (NTP 

1989). The relevance of these uterine effects in animals to humans is not known. 

In addition to uterine effects, limited studies of reproduction and development in mice have shown effects. 

A small increase in the average duration of the estrous cycle was observed in mice exposed to 15,000 ppm 

chloroethane 6 hours/day for 21 days (Bucher et al. 1995). Before the exposure, estrous cycle duration was 

5.15±0.15 days, while during the exposure, estrous cycle duration was 5.52±0.19 days. Measurement of 

serum estradiol and progesterone did not reveal any consistent statistically significant changes attributable 

to chloroethane exposure. Evidence of fetotoxicity, a statistically significant increase in small centers of 

unossified bones of the skull, was observed in the offspring of mice exposed to 4,946 ppm chloroethane 

during gestation days 6-15 (Scortichini et al. 1986). Further studies are needed to confirm the reproductive 

and developmental toxicity of chloroethane and to determine that the effects are observed in another 

species in addition to mice. 

Chloroethane is an alkylating agent and is mutagenic to Samonella (NTP 1989). Chloroethane has not 

been shown to cause genotoxic effects in in vivo assays in mice (Ebert et al. 1994). In a single highconcentration (15,000 ppm) study, chloroethane clearly caused uterine cancer in female mice, with 

equivocal evidence of carcinogenicity in rats (increased skin tumors in male rats and astrocytomas in the 

brains of female rats) (NTP 1989). Because only one concentration was tested, it cannot be determined 

whether or not the carcinogenic effect of chloroethane is a high-concentration phenomenon. 
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Minimal Risk Levels for Chloroethane 

Inhalation MRLS 

•	 An MRL of 15 ppm has been derived for acute-duration inhalation exposure (14 days or less) to 

chloroethane. 

This MRL is based on the developmental study by Scortichini et al. (1986) in which minimal 

fetotoxicity (a significant increase in the incidence of foramina of the skull bones) was observed in the 

offspring of mice exposed to 4,946 ppm chloroethane during gestation days 6-15. Fetotoxicity was not 

observed at 1,504 ppm, the NOAEL concentration that serves as the basis of the MRL. No additional 

developmental studies of chloroethane were identified. 

Intermediate- and chronic-duration inhalation MRLs were not derived. The only concentration that 

resulted in adverse effects in longer duration studies was 15,000 ppm (NTP 1989). At this concentration in 

studies of about 2 years in duration, hyperactivity, renal effects, and decreased survival were observed in 

mice. In 13-week studies, no adverse effects were observed in rats or mice at 19,000 ppm (NTP 1989). 

Since the acuteduration inhalation MRL is based on a concentration much lower than those resulting in 

effects in longer duration studies, it should also be protective for intermediate- and chronic-duration 

inhalation exposure. 

Oral MRLS 

Oral data concerning the effects of chloroethane were not identified. Therefore, no oral MRLs were 

derived. 

Death. Acute inhalation of high concentrations of chloroethane vapor is lethal to humans (Dawkins 

1964; Konietzko 1984; Kuschinsky 1970; Lawson 1965; Lehman and Flury 1943; Yacoub et al. 1993) and 

animals (Lazarew 1929; Sayers et al. 1929; Troshina 1966). Death appears to be caused by asphyxiation, 

as well as effects on the heart and nervous system. The nervous system seems to be involved because 

neurological effects such as unsteadiness, loss of muscle coordination, and unconsciousness precede death 

in animals. Similar effects are seen in humans exposed to chloroethane. In addition, effects such as 

respiratory paralysis and cardiac depression, which have been reported during chloroethane exposure in 

both humans and animals, are at least partly neurological in origin. For example, cardiac depression can be 

caused by stimulation of the vagus nerve or by direct effect on the cardiac tissue. Bush et al. (1952) found 

that in dogs anesthetized with chloroethane, cardiac depression occurred first by vagal stimulation and 

then by direct effect on the heart. Upon overdose, the dogs died from cardiac arrest. Most human deaths 

caused by chloroethane were the result of overdose while under anesthesia. There is also one report of a 

death following abuse of chloroethane 
CHLOROETHANE 64 

2. HEALTH EFFECTS 

(Yacoub et al. 1993). The specific level of exposure that causes death in humans is not known, but it 

probably exceeds 40,000 ppm, which is the concentration that was typically used to produce clinical 

anesthesia. Chloroethane is no longer used as a general anesthetic in the United States. 

The long-term survival of mice was reduced by chronic exposure to 15,000 ppm chloroethane vapor (NTP 

1989). An ascending urinary tract infection may have contributed to the reduced survival in male mice. 

The decreased survival in female mice was attributed to uterine cancer. Decreased survival was not 

observed in rats, but control survival was abnormally low for this species which obscured the results (NTP 

1989). There is no evidence that humans would respond to chronic chloroethane exposure in a manner 

similar to the mouse, but these data suggest the possibility that sub-anesthetic concentrations of 

chloroethane may be potentially hazardous to humans if inhaled for an extended period of time. 

Reliable information regarding death of humans or animals following oral consumption of chloroethane 

was not found. Because chloroethane is a gas, accidental oral exposure to doses of chloroethane large 

enough to result in deaths is highly unlikely. Although no studies of the acute lethality of dermally-applied 

chloroethane were located, it is unlikely that brief dermal exposure is lethal to humans since chloroethane 

is in widespread use as a topical anesthetic, and reports of accidental death from this use were not found. 

Further, as previously discussed, chloroethane is expected to evaporate quickly from the skin since its 

standard state is a gas. Therefore, it is unlikely to remain on the skin long enough to be absorbed at a dose 

that would result in death. 

Systemic Effects. The systemic effects of chloroethane, which is a gas, have not been studied by the 

oral route of exposure. Few studies regarding dermal exposure to chloroethane were identified. Therefore, 

in the following discussion, unless stated otherwise, exposure is via inhalation. 

Respiratory Effects. When used as a general anesthetic, chloroethane sometimes increases the respiratory 

rate of humans (Cole 1956, 1967). Respiratory paralysis was reported to be the cause of death of a 14-year 

old who died during anesthesia (Kuschinsky 1970). Mild lung effects have also been reported in animals 

exposed to very high concentrations of chloroethane for short periods of time (Gohlke and Schmidt 1972; 

Sayers et al. 1929). Histopathological changes in the lungs of animals were not observed in studies of 

longer duration (Landry et al. 1982, 1987,1989; NTP 1989). 
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The exposure concentrations (up to 19,000 ppm) used in the inhalation studies are much higher than one is 

likely to encounter in occupational settings or in the vicinity of hazardous waste sites. Therefore, 

respiratory effects resulting from chloroethane exposure are highly unlikely. 

Cardiovascular Effects. Chloroethane has been shown to interfere with cardiac function in animals when 

inhaled at anesthetic concentrations. Cardiac depression, ventricular tachycardia, ventricular fibrillation, 

asystole, and sensitization to endogenous and exogenous epinephrine have all been observed in 

dogsanesthetized with chloroethane (Bush et al. 1952; Haid et al. 1954; Morris et al. 1953). Severe, 

irreversible, contractile failure of the heart occurred in a guinea pig heart-lung preparation after exposure 

to chloroethane vapor, and elevated ratios of ATP/ADP and creatine-P/inorganic-P were found in the 

heart, indicating that a reduction in high-energy phosphate utilization had taken place (Doring 1975). 

These results, together with the previously reported finding of cardiac depression in humans exposed 

briefly to high concentrations of chloroethane (Bush et al. 1952), suggest that high levels of chloroethane 

vapor in the air may be potentially hazardous to humans because of effects on the heart. Longer studies at 

lower concentrations have not reported any histopathological changes in the heart (Landry et al. 1982, 

1987,1989; NTP 1989). Cardiovascular effects are unlikely to occur at concentrations of chloroethane 

normally found at occupational settings or in the environment, including hazardous waste sites. 

Gastrointestinal Effects. Abdominal cramps and nausea have been reported by persons exposed to 

chloroethane at very high concentrations for short periods of time (Davidson 1925; Sayers et al. 1929). 

Vomiting has also been reported in patients as they recovered from chloroethane anesthesia (Cole 1967). It 

is not clear if gastrointestinal effects are a direct irritant effect of chloroethane or if they are secondary to 

nervous system effects. Histopathological changes in the gastrointestinal tract of animals were not 

observed in longer studies (Landry et al. 1982, 1987, 1989; NTP 1989). Gastrointestinal tract effects are 

unlikely to occur at concentrations of chloroethane normally found at occupational settings or in the 

environment, including hazardous waste sites. 

Hematological Effects. Cyanosis has been reported in humans following inhalation exposure to 

chloroethane at very high concentrations (Davidson 1925). Since this effect was observed when 

chloroethane was not mixed with oxygen, it is very likely that it was the result of a lack of oxygen rather 

than a direct effect of chloroethane. Hematological effects were not observed in mice exposed to 

chloroethane for 11 days (Landry et al. 1987, 1989) or in rats or dogs exposed to chloroethane for 2 weeks 

(Landry et al. 1982). 
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Based on the available animal data, hematological effects in humans are unlikely to occur at 

concentrations of chloroethane normally found at occupational settings or in the environment, including 

hazardous waste sites. 

Musculoskeletal Effects. No studies were located regarding musculoskeletal effects in humans following 

exposure to chloroethane. Histopathological changes in the muscle and bone have not been observed in 

animals following inhalation exposure (Landry et al. 1982, 1987, 1989; NTP 1989). Disintegration of 

muscle fibers has been observed in rats after chloroethane was applied dermally until the skin was 

blanched (Kenig 1956). This study suggests that improper use of chloroethane as a topical anesthetic could 

result in adverse effects on the underlying muscle. Musculoskeletal effects in humans are unlikely to occur 

at concentrations of chloroethane normally found at occupational settings or in the environment, including 

hazardous waste sites. 

Hepatic Effects. An enlarged liver and mild transient disturbance of liver function were reported in a 

woman who sniffed chloroethane for 4 months (Hes et al. 1979). Moderately elevated serum alanine 

aminotransferase was observed in a man who abused chloroethane for 30 years (Nordin et al. 1988). Liver 

effects reported in animals exposed to high concentrations of chloroethane include an increase in the liver 

ATP/ADP ratio (Oura et al. 1966), decreased liver glutathione (Fedtke et al. 1994b), and decreased liver 

non-protein sulfhydryl concentrations (Landry et al. 1982). Increased liver weights have also been reported 

(Landry et al. 1982,1987, 1989). These mild liver effects may be considered an adaptive response to 

chloroethane exposure rather than a toxicologic effect. Other studies have not reported liver weight 

changes or histopathological changes in the liver (Bucher et al. 1995; NTP 1989). Based on the available 

data, hepatic effects in humans are unlikely to occur at concentrations of chloroethane normally found at 

occupational settings or in the environment, including hazardous waste sites. 

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

chloroethane. Mild signs of nephrotoxicity were observed in mice exposed to relatively high 

concentrations for 100 weeks (NTP 1989), while no renal effects were observed in rats exposed at the 

same concentrations for 102 weeks (NTP 1989). Additional acute- and intermediate-duration studies have 

not reported significant renal effects in animals (Fedtke et al. 1994a; Landry et al. 1982, 1987, 1989; NTP 

1989; Schmidt et al. 1972). Based on the available animal data, renal effects in humans are unlikely to 

occur at concentrations of chloroethane normally found at occupational settings or in the environment, 

including hazardous waste sites. 
CHLOROETHANE 67 

2. HEALTH EFFECTS 

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

chloroethane. Endocrine gland effects have not been observed in animals exposed to chloroethane (Gohlke 

and Schmidt 1972; Landry et al. 1982, 1987, 1989; NTP 1989; Schmidt et al. 1972). Based on the 

available animal data, endocrine effects in humans are unlikely to occur at concentrations of chloroethane 

normally found at occupational settings or in the environment, including hazardous waste sites. 

Dermal Effects. No studies were located regarding dermal effects in humans following inhalation exposure 

to chloroethane. Following inhalation exposure of animals to chloroethane, dermal effects have not been 

reported (Landry et al. 1982, 1987, 1989; NTP 1989). Chloroethane has a local anesthetic effect in humans 

and animals following dermal application. It rapidly evaporates and draws heat from the skin, causing the 

skin to freeze. Application for too long a time can result in frostbite. Noble (1979) reported frostbite in 

three children sprayed with chloroethane for several minutes. Contact dermal sensitivity has also been 

reported in persons exposed to chloroethane (Bircher et al. 1994; Kriechbaumer et al. 1998; Van Ketel 

1976). Chloroethane applied to rats until the skin was blanched caused edema in the subcutaneous tissue 

at the site of application (Kenig 1956). Because chloroethane is used as a topical anesthetic, many people 

may be at risk of developing sensitivity to chloroethane or of the hazard of freezing of the skin if 

chloroethane is used incorrectly. Sensitized individuals may react to chloroethane in the environment or at 

hazardous waste sites. 

Ocular Effects. Mild eye irritation has been reported in volunteers exposed briefly to very high 

concentrations of chloroethane (Sayers et al. 1929). Effects on the eyes have not been reported in animals 

exposed to chloroethane (Landry et al. 1982, 1987,1989). Based on the available data, ocular effects in 

humans are unlikely to occur at concentrations of chloroethane normally found at occupational settings 

and in the environment, including hazardous waste sites. 

Body Weight Effects. Body weight effects have not been reported in animals exposed to chloroethane 

(Fedtke et al. 1994a; Landry et al. 1982,1987,1989; NTP 1989; Schmidt et al. 1972; Scortichini et al. 

1986). Based on the available animal data, body weight effects in humans are unlikely to occur at 

concentrations of chloroethane normally found at occupational settings and in the environment, including 

hazardous waste sites. 
CHLOROETHANE 68 

2. HEALTH EFFECTS 

Immunological and Lymphoreticular Effects. No immunological effects were reported in 

humans (Troshina 1966) or animals (Landry et al. 1982, 1987, 1989; NTP 1989; Schmidt et al. 1972) after 

inhalation exposure to chloroethane, but contact dermatitis has been found in humans treated dermally 

with chloroethane (Bircher et al. 1994; Van Ketel 1976). This effect is notable because of the widespread 

use of chloroethane as a topical anesthetic. Sensitized individuals may react to chloroethane in the 

environment or at hazardous waste sites. 

Neurological Effects. Chloroethane has a general anesthetic effect when inhaled at high 

concentrations by humans and animals. The severity of the effect increases with the concentration of 

chloroethane and the duration of exposure. In humans, unconsciousness was produced by inhalation of 

33,600 ppm chloroethane for approximately 15 minutes (Davidson 1925). Cbloroethaue is no longer used 

as a general anesthetic in the United States, but in the past, concentrations of approximately 40,000 ppm 

were used clinically to produce anesthesia (Lawson 1965). The gastrointestinal effects reported in patients 

as they recovered from chloroethane anesthesia (Cole 1967; Davidson 1925; Sayers et al. 1929) may be 

secondary to the neurological effects. In animals, clinically effective anesthetic concentrations range from 

30,000 to 45,000 ppm (Dobkin and Byles 1971). Induction of anesthesia using chloroethane is rapid, and 

so is recovery. The anesthetic effect is thought to be produced by the compound itself; however, its 

mechanism of action is unknown. Balasubramanian and Wetlaufer (1966) showed that the vapors 

produced from pure liquid chloroethane and other volatile anesthetics produced reversible structural 

changes in globular proteins in vitro. They proposed that the anesthetic activity of these compounds might 

be due to their ability to produce structural changes in protein or lipoprotein structures in cell membranes. 

Following abuse of chloroethane, ataxia, nystagmus, scanning dysarthria, dysdiadochokinesia of the arm, 

and sluggish lower limb reflexes were reported (Hes et al. 1979). These effects were reversible after 1 

month without chloroethane exposure. In a second case of chloroethane abuse, neurological and mental 

changes (grand ma1 seizure, ataxia, difficulties in walking, disorientation, short-term memory impairment, 

visual hallucinations) were observed following recovery after 30 years of chloroethane abuse (Nordin et al. 

1988). The study authors indicate that it was not possible to determine whether the nervous system effects 

were toxic effects of chloroethane or withdrawal symptoms. 

Animal studies examining the histology of nervous system tissue have not revealed any adverse effects 

following inhalation exposure (Gohlke and Schmidt 1972; Landry et al. 1982, 1987, 1989; NTP 1989; 

Schmidt et al. 1972). Except for observations during exposure, neurological function has not been studied 

in animals following intermediate or chronic inhalation exposure. 
CHLOROETHANE 69 

2. HEALTH EFFECTS 

Chloroethane is still used as a local anesthetic It is applied to the skin, and its rapid evaporation results in 

cooling. Mild pain has been reported during the dermal application of chloroethane to the skin of humans 

(Selby and Bowles 1995). Application of chloroethane to the skin of rats has been reported to result in 

thickening of nerve fibers and swelling of Schwann cell nuclei (Kenig 1956). 

The nervous system is a target of chloroethane exposure, and functional effects of chloroethane exposure 

have not been well studied. Therefore, it is not known if neurological effects may occur in humans at 

concentrations of chloroethane normally found at occupational settings and in the environment, including 

hazardous waste sites. 

Reproductive Effects. Studies of reproductive effects in humans exposed to chloroethane were not 

identified. Several studies investigated reproductive endpoints in animals. In dogs anesthetized with 

chloroethane, high concentrations resulted in decreased uterine motility and muscle tone (Van Liere et al. 

1966). Uterine weight was decreased by approximately 35% in mice exposed to high concentrations of 

chloroethane (Fedtke et al. 1994a). Significant decreases in uterine glutathione levels have also been 

reported in rats and mice exposed to chloroethane (Fedtke et al. 1994b). The decreases in glutathione in 

the uterus were greater than the decreases in glutathione observed in the liver, lungs, and kidneys. A small 

increase in the average duration of the estrous cycle was observed in mice exposed to high concentrations 

of chloroethane 6 hours/day for 2 1 days (Bucher et al. 1995). Measurement of serum estradiol and 

progesterone did not reveal any consistent statistically significant changes attributable to chloroethane 

exposure. Sperm motility in rats was reduced after exposure to chloroethane for 6 months (Troshina 1966). 

Histopathological effects have not been observed in reproductive organs of animals exposed to 

chloroethane (Landry et al. 1982, 1987, 1989; NTP 1989). No effects on the number of live and dead 

fetuses or the number and position of resorption sites were observed in mice exposed to chloroethane 

during gestation days 6-15 (Scortichini et al. 1986). Additional studies of reproductive outcome in animals 

following inhalation exposure to chloroethane were not identified. 

Based on decreases in uterine glutathione in rats and mice, decreases in uterine weight in mice, and the 

development of uterine cancer in mice exposed to chloroethane (NTP 1989) (see Cancer discussion in 

Section 2.5), the uterus appears to be a target of chloroethane exposure in mice; rats are apparently less 

sensitive to these effects. Further studies are required to determine the mechanism of uterine toxicity in 

mice and to determine the relevance of these effects to humans exposed to chloroethane at concentrations 

normally found at occupational settings and in the environment, including hazardous waste sites. 
CHLOROETHANE 70 

2. HEALTH EFFECTS 

Developmental Effects. No studies were located regarding developmental effects in humans 

following exposure to chloroethane. Only one study of the developmental effects of chloroethane in 

animals was found. In this mouse study, minimal evidence of fetotoxicity (increase in small centers of 

unossified bones of the skull) was observed at the highest concentration tested (Scortichini et al. 1986). 

This study serves as the basis for the acute-duration inhalation MRL. Further study is required to 

determine the relevance of developmental effects in animals to humans exposed to chloroethane at 

concentrations normally found at occupational settings and in the environment, including hazardous waste 

sites. 

Genotoxic Effects. Results of mutagenicity tests performed in vivo and in vitro are shown in Tables 

2-2 and 2-3, respectively. Chloroethane did not increase the number of micronuclei in bone marrow cells 

or affect DNA synthesis in mice exposed nose-only to 25,000 ppm chloroethane 6 hours/day for 3 days 

(Ebert et al. 1994). The investigators indicated that the exposure concentration used in this study was 

about 66% of the flammability limit and that it was the highest concentration that could be safely 

administered. Using a desiccator for exposure to the gas, positive rest&s in reverse mutation assays using 

Salmonella typhimurium strain TA1535 with and without activation were reported by NTP (1989). In 

strain TAl00, the results were positive only with metabolic activation, while the results were negative in 

strain TA98 both with and without metabolic activation. NTP (1989) indicated that the mutagenic activity 

of chloroethane in S. typhimurium was consistent with an alkylating agent. Chloroethane was positive for 

gene mutation in Chinese hamster ovary cells exposed in vitro (Ebert et al. 1994). Negative results were 

reported for chloroethane in a cell transformation assay using mouse BALB/c-3T3 cells (Tu et al. 1985). 

Although chloroethane is mutagenic in in vitro assays, negative results were observed in in vivo studies, 

and the data are insufficient to predict that chloroethane poses a genotoxic threat to humans. 

Existing data are inconclusive concerning the genotoxicity of chloroethane. Despite this lack of data, the 

volatility of chloroethane, its rapid clearance from the body, and its quick metabolism within the body 

indicate it is unlikely that it would reach germ cells to result in any potential genotoxic effect. 

Cancer. No studies were located regarding the carcinogenicity of chloroethane in humans, but 

chloroethane has been shown to be carcinogenic in animals. In a study by the NTP (1989), 86% of female 

mice chronically exposed to chloroethane vapor developed highly malignant uterine carcinomas. Uterine 

tumors were not observed in any of the control mice. The incidence of hepatocellular carcinomas also 

increased significantly in female mice. Male mice had an increased incidence of alveolar and bronchiolar 

adenomas, but because male survival was substantially reduced toward the end of the study these results 

are not conclusive. Male 


CHLOROETHANE 73 

2. HEALTH EFFECTS 

rats had marginally increased incidences of skin tumors, and female rats had marginally increased 

incidences of brain astrocytomas, providing equivocal evidence that chloroethane is carcinogenic in rats 

(NTP 1989). The fact that chloroethane is carcinogenic in mice and may be carcinogenic in rats as well 

suggests the possibility that this compound may also be carcinogenic in humans. Based on limited 

evidence of carcinogenicity in animals and no human data, IARC (1991) considers chloroethane to be in 

Group 3, not classifiable as to its carcinogenicity to humans. The carcinogenicity of chloroethane has not 

been classified by EPA (IRIS 1997) or NTP (DHHS 1994). The data are not sufficient to predict whether 

chloroethane is carcinogenic at concentrations that occur in the environment or at hazardous waste sites. 

OSHA has recommended that ethyl chloride be treated in the workplace with caution because of the 

structural similarity to the four confirmed halogenated animal carcinogens: ethylene dichloride; 

hexachloroethane; 1,1,2,2-tetrachloroethane; and 1,1,2-trichloroethane (NIOSH 1997). 

2.6 CHILDREN’S SUSCEPTIBILITY 

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

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

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

effects on the fetus and neonate due to 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 5.6 Exposures of Children. 

Children sometimes differ from adults in their susceptibility to hazardous chemicals, but whether there is a 

difference depends on the chemical (Guzelian et al. 1992; NRC 1993). Children may be more or less 

susceptible than adults to health effects and the relationship may change with developmental age 

(Guzelian et al. 1992; NRC 1993). Vulnerability often depends on developmental stage. There are critical 

periods of structural and functional development during both pre-natal and post-natal life and a particular 

structure or function will be most sensitive to disruption during its critical period(s). Damage may not be 

evident until a later stage of development. There are often differences in pharmacokinetics and metabolism 

between children and adults. For example, absorption may be different in neonates because of the 

immaturity of their gastrointestinal tract and their larger skin surface area in proportion to body weight 

(Morselli et al. 1980; 
CHLOROETHANE 74 

2. HEALTH EFFECTS 

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 (Widdowson and 

Dickerson 1964; Foman et al. 1982; Owen and Brozek 1966; Altman and Dittmer 1974; Foman 1966). 

The infant also has an immature blood-brain barrier (Adinolfi 1985; Johanson 1980) and probably an 

immature blood-testis barrier (Setchell and Waites 1975). Many xenobiotic metabolizing enzymes have 

distinctive developmental patterns and 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 (Leeder and Kearns 1997; Komori 1990; Vieira et al. 1996; NRC 1993). 

Whether differences in xenobiotic metabolism make the child more or less susceptible also depend on 

whether the relevant enzymes are involved in activation of the parent compound to its toxic form or in 

detoxification. There may also be differences in excretion, particularly in the newborn who has a low 

glomerular filtration rate and has not developed efficient tubular secretion and resorption capacities 

(Altman and Dittmer 1974; West et al. 1948; NRC 1993). Children and adults may differ in their capacity 

to repair damage from chemical insults. Children also have a longer lifetime in which to express damage 

from chemicals; this potential is particularly 

relevant to cancer. 

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

decrease susceptibility to the same chemical. For example, the fact that infants breathe more air per 

kilogram of body weight than adults may be somewhat counterbalanced by their alveoli being less 

developed, so there is a disproportionately smaller surface area for absorption (NRC 1993). 

Children have infrequently been observed for health effects following exposure to chloroethane. Effects 

observed in humans exposed to chloroethane have resulted primarily from inhalation exposure. 

Respiratory paralysis was reported to be the cause of death of a 14-year-old child who died during 

anesthesia with chloroethane (Kuschinsky 1970); however, the concentration of chloroethane administered 

was not known. Another study reported vagal stimulation, followed by depression of cardiac tissues in 

children exposed briefly to reportedly high concentrations of chloroethane; the specific levels were not 

indicated (Bush et al. 1952). 

Chloroethane has also been used and sometimes misused as a topical anesthetic in both children and adults 

(Nielsen 1980; Noble 1979; Ott 1969; Van Ketel 1976). Misuse occurs when excessive amounts of 

chloroethane are sprayed on the skin for long periods of time. Three children suffered frostbite on the 
CHLOROETHANE 75 

2. HEALTH EFFECTS 

exposed skin of their ears and necks after having their earlobes sprayed with chloroethane for several 

minutes (Noble 1979). 

Effects seen in adults exposed to chloroethane are also expected in children. In particular, the nervous 

system is likely to be a sensitive target of chloroethane, as it is in adults. Since infants and young children 

have a larger proportion of their bodies as brain mass, and since blood flow is greater to this organ in 

children, one might predict on pharmacokinetic grounds that these ages of children would be more 

susceptible to the anesthetic effects of chloroethane than adults In addition, chloroethane distribution may 

be very different in children relative to adults due to the difference in fat and water content and lean body 

mass in children. 

No studies were identified that reported effects caused by chloroethane in adults exposed as children and 

there is no information on the health effects of exposures in immature animals. There are no data 

concerning the effects of chloroethane exposure on human development and there is only one 

developmental study in animals. This study (Scortichini et al. 1986) reported that at the highest 

concentration administered to mice, delayed ossification of skull bones occurred. However, no other 

developmental parameters were affected, and no maternal toxicity was reported. 

There are no data available concerning the pharmacokinetics of chloroethane in children. There are no 

human or animal studies available concerning the ability of chloroethane or its metabolites to reach and 

cross the placenta. One study determined that chloroethane can be detected in the breast milk of nursing 

mothers (Pelizzari et al. 1982), but the study was not quantitative and did not offer data concerning the 

percentage of nursing mothers that might excrete the compound in milk after exposure, nor did it provide a 

range of concentrations of the compound in this medium. No studies were identified that determined if 

chloroethane was stored in maternal tissues. However, the rapid clearance of chloroethane, as well as its 

volatility, suggest that it would not be stored within the body for an extended period of time, so preconception maternal exposure is not likely to result in exposure to children during gestation or lactation. 

See Section 2.3 for further information. 

No data are currently available to indicate that the metabolism of chloroethane is different in children 

when compared to adults; however, some of the enzymes in the chloroethane metabolism scheme belong 

to enzyme families that are developmentally regulated to some extent either in humans or animals. 

Chloroethane is metabolized by both cytochrome P450 and by glutathione S-transferase. Studies have 

shown that liver glutathione S-transferase activities are low in prepubertal male and female rats, but as the 

rats reach sexual 
CHLOROETHANE 76 

2. HEALTH EFFECTS 

maturity (at around 30-50 days of age), glutathione-conjugating activity toward dichloronitrobenzene is 

two to threefold higher in males than females (Lamartiniere and Lucier 1983). The difference in 

glutathione S-transferase activity was dependent on pituitary secretions. Further research on 

hypophysectomized male and female rats revealed that growth hormones may contribute to the 

establishment of glutathione S-transferase activities (Lamartiniere 198 1). No data are available to indicate 

that glutathione S-transferase activity is also developmentally or sexually expressed in humans. 

After glutathione conjugation of chloroethane, three other enzymes convert the conjugate to a more 

hydrophilic form to be excreted by the body. These enzymes are γ-glutamyltranspeptidase, cysteinyl 

glycinase, and N-acetyltransferase, NAT (Amdur et al. 1991). These three enzymes convert relatively 

hydrophobic glutathione conjugates to their respective mercapturic acids, which can be excreted more 

readily. There are two N-acetyltransferase enzyme families, NAT 1 and NAT2. Of these enzymes, only 

NAT2 is developmentally regulated. It is unknown which NAT enzyme metabolizes chloroethane; 

therefore, it is unknown whether chloroethane is developmentally regulated by this pathway. 

Studies have shown that cytochrome P450 IIEl is developmentally expressed in humans (Vieira et al. 

1996). This enzyme is not detectable from livers of fetuses at 14-40 gestational weeks. However, the level 

of the protein rises sharply in the first day after birth (1 unit/mg protein), and continues to increase until it 

reaches adult values of approximately 5 units/mg protein, in children from 1 to 10 years of age (Vieira et 

al 1996). 

It is unknown whether children differ from adults in their susceptibility to chloroethane, despite the 

theoretical reasons for which they might potentially differ, as discussed above. 

There are no data concerning parental exposure affecting children, including pre-conception exposure. 

There are no data concerning pre-conception exposure of either parent to germ line mutations, 

developmental defects, childhood cancer, or other health effects. Chloroethane is positive in in vitro 

mutagenicity studies in bacterial and mammalian cells, but is negative in in vivo mammalian cell tests. 

These inconclusive results do not allow the prediction of chloroethane genotoxicity in humans. 

2.7 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). 
CHLOROETHANE 77 

2. HEALTH EFFECTS 

Due to a nascent understanding of the use and interpretation of biomarkers, implementation of biomarkers 

as tools of exposure in the general population is very limited. A biomarker of exposure is a xenobiotic 

substance or its metabolite(s), or the product of an interaction between a xenobiotic agent and some target 

molecule(s) or cell(s) that is measured within a compartment of an organism (NAS/NRC 1989). The 

preferred biomarkers of exposure are generally the substance itself or substance-specific metabolites in 

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

interpretation of biomarkers of exposure. The body burden of a substance may be the result of exposures 

from more than one source. The substance being measured may be a metabolite of another xenobiotic 

substance (e.g., high urinary levels of phenol can result from exposure to several different aromatic 

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

conditions (e.g., duration and route of exposure), the substance and all of its metabolites may have left the 

body by the time samples can be taken. It may be difficult to identify individuals exposed to hazardous 

substances that are commonly found in body tissues and fluids (e.g., essential mineral nutrients such as 

copper, zinc, and selenium). 

Biomarkers of exposure to chloroethane are discussed in Section 2.7.1. 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 chloroethane 

are discussed in Section 2.7.2. 

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 2.9, Populations That Are Unusually Susceptible. 

There are no known biomarkers of exposure or effect that have been validated in children or adults 

exposed as children. There are no known biomarkers of exposure and effect that are unique to children. 

Further, there are no known biomarkers of exposure and effect in adults that could identify childhood 

exposure. Since 
CHLOROETHANE 78 

2. HEALTH EFFECTS 

chloroethane is rapidly metabolized in the body, biomarkers for adults or children would be limited to 

current exposures. 

2.7.1 Biomarkers Used to Identify or Quantify Exposure to Chloroethane 

Studies of the association of environmental concentrations of chloroethane with levels of chloroethane in 

the breath, fluids, and body tissues were not identified. Because a portion of the chloroethane inhaled is 

exhaled, measurement of chloroethane in breath may serve as a useful biomarker of exposure. In rats and 

mice, chloroethane is metabolized to acetaldehyde and the glutathione conjugates, S-ethyl-N-acetyl-Lcysteine and S-ethyl-L-cysteine (Fedtke et al. 1994a, 1994b). Further research is required to determine if 

urinary excretion of glutathione conjugates would serve as a useful biomarker following exposure of 

humans to chloroethane. The glutathione conjugates S-ethyl-N-acetyl-E-cysteine and S-ethyl-L-cysteine 

would not be biomarkers unique to chloroethane exposure. Acetaldehyde forms adducts with plasma 

proteins. Because ethanol is also metabolized to acetaldehyde, it has been suggested that the measurement 

of these adducts, or of antibodies produced in response to these adducts, may serve as a biomarker of 

ethanol exposure (Won-all et al. 1994). The measurement of acetaldehyde protein adducts, or the 

associated antibodies, may also serve as a biomarker of chloroethane exposure. It should be noted that 

formation of antibodies to these compounds can result from exposure to chemicals other than 

chloroethane. 

2.7.2 Biomarkers Used to Characterize Effects Caused by Chloroethane 

Anesthesia is rapidly produced in humans by inhalation of chloroethane at a concentration of 

approximately 40,000 ppm. Other effects reported at anesthetic concentrations include cardiac 

irregularities, respiratory paralysis, and nausea. A blood concentration of 20-30 mg percent was reported 

for this exposure level (Adriani 194 1). No other studies were located regarding levels of chloroethane in 

human tissues and fluids associated with effects. Because these effects occur following exposure to many 

chemicals, they would not serve as useful biomarkers for chloroethane exposure. 

For more information on biomarkers for renal and hepatic effects of chemicals see ATSDR/CDC 

Subcommittee Report on Biological Indicators of Organ Damage (1990), and for information on 

biomarkers for neurological effects see OTA (1990). 
CHLOROETHANE 79 

2. HEALTH EFFECTS 

2.8 INTERACTIONS WITH OTHER CHEMICALS 

The interaction between chloroethane and ethanol was studied by Schmidt et al. (1972) and Gohlke and 

Schmidt (1972), who found that chloroethane enhanced the effects of ethanol in rats. Inhalation of 

chloroethane 4 hours/day for 8 of 10 days in conjunction with ethanol treatment led to greater changes in 

liver enzyme levels (decreased succinate dehydrogenase and nonspecific esterase and increased acid 

phosphatase) than were produced by ethanol alone. In addition, inflammation of the liver and fatty 

degeneration of hepatocytes were most prominent in rats given chloroethane in addition to ethanol. These 

results, although limited, are interesting because both ethanol and chloroethane are metabolized by 

CYP2El to acetaldehyde. Therefore, one compound could compete for active sites in CYP2E1, resulting 

in delayed metabolism of the other compound. However, ethanol, as well as chloroethane, induces 

CYP2El to expression, so more enzyme should be produced to handle a metabolic challenge (Leeder and 

Kearns 1997). 

A study in cats demonstrated that the extent of methemoglobinemia induced by intravenous administration 

of aniline was significantly reduced in cats anesthetized with chloroethane compared to unanesthetized 

cats (McLean et al. 1967). The rate at which the methemoglobin disappeared, however, was also 

significantly reduced in the anesthetized cats compared with unanesthetized cats. The results suggest that 

concurrent exposure to aniline and chloroethane may induce less methemoglobin than exposure to aniline 

alone, but the methemoglobin induced by the combined exposure would persist longer than that induced 

by exposure to aniline alone. A similar effect was not observed when cats were anesthetized with 

chloralose and treated with phenylhydroxylamine, the aniline metabolite that results in methemoglobin 

formation. Therefore, the study authors concluded that chloralose acts by inhibiting the metabolism of 

aniline. It is not known if chloroethane acts in the same manner. 

No studies were available investigating the interactions of chloroethane with other chemicals in children or 

in adults. 

2.9 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE 

A susceptible population will exhibit a different or enhanced response to chloroethane than will most 

persons exposed to the same level of chloroethane in the environment. Reasons may include genetic 

makeup, age, health and nutritional status, and exposure to other toxic substances (e.g., cigarette smoke). 

These parameters may result in reduced detoxification or excretion of chloroethane, or compromised 

function of 
CHLOROETHANE 80 

2. HEALTH EFFECTS 

target organs affected by chloroethane. Populations who are at greater risk due to their unusually high 

exposure to chloroethane are discussed in Section 5.7, Populations with Potentially High Exposure. 

Persons with prior exposure to ethanol may be at higher risk from chloroethane exposure because 

chloroethane has been shown to enhance the effects of ethanol in rats (Gohlke and Schmidt 1972; Schmidt 

et al. 1972). Because chloroethane is metabolized by the liver (Fedtke et al. 1994a, 1994b), and minimal 

liver effects have been observed in animals following inhalation exposure (Landry et al. 1987, 1989; Oura 

et al. 1966; Sayers et al. 1929; Troshina 1966), persons with compromised liver function may be at greater 

risk following exposure to chloroethane. 

It is unknown whether children differ in their susceptibility to chloroethane from adults. This is discussed 

in detail in 2.6 Children’s Susceptibility. 

2.10 METHODS FOR REDUCING TOXIC EFFECTS 

This section will describe clinical practice and research concerning methods for reducing toxic effects of 

exposure to chloroethane. 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 chloroethane. When 

specific exposures have occurred, poison control centers and medical toxicologists should be consulted for 

medical advice. The following texts provide specific information about treatment following exposures to 

chloroethane: Bronstein AC, Currance PL. 1988. Emergency Care for Hazardous Materials Exposure; 

Haddad LM, Winchester H. 1990. Clinical Management of Poisoning and Drug Overdose; Stutz DR, Ulin 

S. 1992. Hazardous Materials Injuries. 

There are no known pediatric-specific methods for reducing peak absorption following exposure or 

reducing body burden. None of the methods for reducing peak absorption or body burden are 

contraindicated in children. No data were available to indicate that the methods used in adults have been 

validated in children. 

2.10.1 Reducing Peak Absorption Following Exposure 

Because chloroethane is a gas, human exposure is most likely to occur by inhalation. Moving the subject 

to fresh air is the best way to reduce absorption of chloroethane following inhalation exposure (Haddad 

and Winchester 1990). 
CHLOROETHANE 81 

2. HEALTH EFFECTS 

2.10.2 Reducing Body Burden 

Animal studies suggest that the body does not retain significant amounts of chloroethane (Fedtke et al. 

1994a, l994b). Because some of the absorbed chloroethane is exhaled, increasing the ventilation rate once 

the subject is removed from exposure may help to enhance elimination. 

2.10.3 Interfering with the Mechanism of Action for Toxic Effects 

No methods for interfering with the mechanism of action of chloroethane were identified. 

2.11 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 chloroethane is available. Where adequate information is not available, 

ATSDR, in conjunction with the National Toxicology Program (NTP), is required to assure the initiation 

of a program of research designed to determine the health effects (and techniques for developing methods 

to determine such health effects) of chloroethane. 

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. 

2.11.1 Existing Information on Health Effects of Chloroethane 

The existing data on health effects of inhalation, oral, and dermal exposure of humans and animals to 

chloroethane are summarized in Figure 2-4. The purpose of this figure is to illustrate the existing 

information concerning the health effects of chloroethane. Each dot in the figure indicates that one or more 

studies provide information associated with that particular effect. The dot does not necessarily imply 

anything about the quality of the study or studies, nor should missing information in this figure be 

interpreted as a “data need.” A data need, as defined in ATSDR’s Decision Guide for Identifying 

Substance-Specific Data Needs 

CHLOROETHANE 83 

2. HEALTH EFFECTS 

Related to Toxicological Profiles (ATSDR 1989), is substance-specific information necessary to conduct 

comprehensive public health assessments. Generally, ATSDR defines a data gap more broadly as any 

substance-specific information missing from the scientific literature. As can be seen from the figure, 

chloroethane exposure by the inhalation route in animals has been well studied; however, there are few 

studies of the health effects of chloroethane exposure by other routes. The lack of studies of oral and 

dermal exposure is consistent with the fact that chloroethane is a gas at room temperature. 

2.11.2 Identification of Data Needs 

Acute-Duration Exposure. Tests of the acute toxicity of chloroethane by inhalation exposure have 

provided information on the levels of chloroethane that produce neurological effects in humans (Davidson 

1925; Sayers et al. 1929) and animals (Landry et al. 1982; Sayers et al. 1929) and the levels that produce 

death in animals (Sayers et al. 1929). Other toxic effects, such as those on the heart, have been reported 

(Bush et al. 1952; Haid et al. 1954), but the precise levels at which they occur have not been identified. 

Studies that carefully examine tissues histologically and look for other subtle effects are needed. They 

might provide information on the mechanisms of chloroethane lethality and neurotoxicity and provide 

further information on other toxic effects. The acute-duration inhalation MRL is based on an acuteduration developmental study in which minimal fetotoxicity was observed in the offspring of mice 

exposed to chloroethane on gestation days 6-15 (Scortichini et al. 1986). 

No reliable studies of the oral or dermal toxicity of chloroethane were located. Reliable oral exposure 

studies are needed. Many people are exposed to chloroethane through its use as a topical anesthetic. 

Frostbite has occurred following prolonged skin application (Noble 1979). Studies of the acute dermal 

toxicity of chloroethane are needed to estimate safe application times. There is one report of eye irritation 

in humans caused by exposure to high concentrations of chloroethane vapor (Sayers et al. 1929), but skin 

irritation has not been studied for any exposure route. 

Intermediate-Duration Exposure. Repeated-dose studies of the toxicity of chloroethane by inhalation 

exposure have been performed in rats (Landry et al. 1982; NTP 1989), mice (Landry et al. 1987, 1989; 

NTP 1989), and dogs (Landry et al. 1982) at several dosage levels and for several durations of exposure. 

Reports indicate that inhalation abuse of chloroethane by adults and children may be increasing (Hersh 

199 1; Walker 1993). Human studies involving chloroethane abusers or animal studies using doses 

comparable to those sniffed from household products are needed to help elucidate the systemic effects 

caused by the compound. 
CHLOROETHANE 84 

2. HEALTH EFFECTS 

Reliable studies of repeated-dose exposure to chloroethane are not available for other routes of exposure. 

Reliable oral exposure studies are needed. Chloroethane is also repeatedly used as a local anesthetic to 

treat sports injuries and in the treatment of musculoskeletal facial pain (Marbach 1996). Repeated-dose 

dermal studies are needed to provide information on whether repeated dermal exposure of humans is 

hazardous. 

Chronic-Duration Exposure and Cancer. A 2-year bioassay on inhaled chloroethane was 

performed in rats and mice by the National Toxicology Program (NTP 1989). Survival of mice was 

reduced compared to controls as a result of ascending urinary tract infections in males and uterine cancer 

in females. The only systemic effects noted were in the kidney (scattered foci of tubular regeneration, 

minimal glomerulosclerosis) in female mice. Female mice were also hyperactive during the exposures. 

Chloroethane was carcinogenic in female mice resulting in uterine cancer (NTP 1989). Because of reduced 

survival of male mice, the study was considered inadequate, although there was an increased incidence of 

alveolar/bronchiolar neoplasms of the lungs. In exposed rats, there was equivocal evidence of 

carcinogenicity based on skin trichoepitheliomas, sebaceous gland adenomas, or basal cell carcinomas in 

males, and malignant astrocytomas in the brain of females. A chronic study in which several exposure 

levels are tested is needed to provide more information on the danger to humans at lower exposure levels. 

Studies of chronic toxicity and carcinogenicity do not exist for other routes of exposure. Therefore, studies 

on chronic oral exposure to chloroethane are needed. 

Genotoxicity. The available genotoxicity studies indicate that chloroethane is mutagenic in bacteria 

(NTP 1989) and in mammalian cells in vitro (Ebert et al. 1994) but not clastogenic in mammalian cells in 

vivo (Ebert et al. 1994). Additional genotoxicity tests are needed to determine whether it is possible that 

chloroethane is genotoxic in humans. 

Reproductive Toxicity. Several studies investigated reproductive endpoints in animals. Uterine 

weight was decreased by approximately 35% in mice exposed to high concentrations of chloroethane 

(Fedtke et al. 1994a). Significant decreases in uterine glutathione levels have also been reported in rats and 

mice exposed to chloroethane (Fedtke et al. 1994b). A small increase in the average duration of the estrous 

cycle was observed in mice exposed to high concentrations of chloroethane (Bucher et al. 1995). 

Measurement of serum estradiol and progesterone did not reveal any consistent statistically significant 

changes attributable to chloroethane exposure. Sperm motility in rats was reduced after exposure to 

chloroethane for 6 months (Troshina 1966). Histopathological effects have not been observed in 

reproductive organs of animals 
CHLOROETHANE 85 

2. HEALTH EFFECTS 

exposed to chloroethane (Landry et al. 1982, 1987, 1989; NTP 1989). No effects on the number of live and 

dead fetuses or on the number and position of resorption sites were observed in mice exposed to 

chloroethane on gestation days 6-15 (Scortichini et al. 1986). 

Based on decreases in uterine glutathione in rats and mice (Fedtke et al. 1994b), decreases in uterine 

weight in mice (Fedtke et al. 1994a), and the development of uterine cancer in mice exposed to 

chloroethane (NTP 1989) (see Cancer discussion in this Section 2.11.2), the uterus appears to be a target 

of chloroethane exposure in mice; rats are apparently less sensitive to these effects. The relevance of 

uterine effects in animals to human chloroethane exposure is not known, and further studies to examine the 

mechanisms of uterine effects observed in chloroethane-exposed mice are needed. A multigeneration study 

to determine if uterine effects, estrous cycle effects, and effects on sperm motility impact reproductive 

performance is also needed. 

Developmental Toxicity. Only one study of the developmental effects of chloroethane in mice 

was 

found. In this study, minimal evidence of fetotoxicity (increase in small centers of unossified bones of the 

skull) was observed at the highest concentration tested (Scortichini et al. 1986). This study serves as the 

basis for the acute-duration inhalation MRL. Additional developmental studies in other species are needed 

Because chloroethane is a neurotoxin, studies of the developmental neurotoxicity of chloroethane are also 

needed to assess the potential risk to humans. 

Immunotoxicity. Several studies included histopathological examinations of immunological organs 

and tissues following inhalation exposure to chloroethane (Landry et al. 1982, 1987, 1989; NTP 1989) but 

found no effects. Studies in which tests of immune function were performed are needed to provide more 

useful information on the immunotoxicity of chloroethane. Three reports on sensitization produced by 

dermally applied chloroethane in humans (Bircher et al. 1994; Kriechbaumer et al. 1998; Van Ketel 1976) 

were found. Because many people are dermally exposed to chloroethane as a topical anesthetic, studies of 

this phenomenon are needed. 

Neurotoxicity. Studies of chloroethane inhalation in humans and animals have provided information 

on the neurological effects produced by acute exposure to chloroethane and the levels at which they occur. 

Most repeated-exposure studies involved only behavioral observations and histopathological examinations 

of neurological organs and tissues; one case report involved a neurological examination of an adult male, 

which revealed marked nystagmus, ataxia and vertigo, but nothing abnormal upon evaluation of the brain, 

brain 
CHLOROETHANE 86 

2. HEALTH EFFECTS 

stem, or spine upon MRI (Walker 1993). In addition, two studies in mice (Landry et al. 1987, 1989) and 

one in dogs (Landry et al. 1982) were identified, neither of which reported signs of neurotoxicity. Reliable 

studies of neurotoxicity following exposure by other routes do not exist. Controlled studies regarding the 

neurological effects of chloroethane are needed. 

Epidemiological and Human Dosimetry Studies. No epidemiological or human dosimetry studies 

of chloroethane have been performed. High inhalation concentrations of chloroethane are anesthetic in 

humans and overdose can be lethal because of cardiovascular or respiratory effects. Chronic inhalation 

exposure has produced cancer in animals (NTP 1989). The general population might be exposed to 

chloroethane by inhalation of contaminated ambient air or intentional use as a topical anesthetic. 

Occupational exposure may occur by inhalation or dermal contact. Epidemiological studies of people who 

live near industries releasing chloroethane or near hazardous waste sites, of people who use chloroethane 

as a topical anesthetic, and of people who are occupationally exposed to chloroethane are needed to 

provide information on whether chloroethane is carcinogenic or has other toxic effects in humans at 

environmentally relevant concentrations. If such effects are identified, human dosimetry studies may be 

able to correlate levels of chloroethane in human tissues or fluids with health effects. 

Biomarkers of Exposure and Effect 

Exposure. Studies of the association of environmental concentrations of chloroethane with levels of 

chloroethane in the breath, fluids, and body tissues were not identified. Studies examining the association 

between air and breath levels of chloroethane are needed. Further research is required to determine if 

urinary excretion of glutathione conjugate metabolites or acetaldehyde-protein adducts (Worrall et al. 

1994) would serve as a useful biomarker following exposure of humans to chloroethane. 

Effect. Unique biomarkers of effect have not been identified for exposure to chloroethane. Further 

research regarding the biochemical effects of chloroethane is needed to identify biomarkers of effect for 

chloroethane. 

Absorption, Distribution, Metabolism, and Excretion. A single breath absorption study (Morgan 

et al. 1970) is the only quantitative study regarding the absorption, distribution, metabolism, and excretion 

of chloroethane in humans. Studies in rats and mice indicate that chloroethane is readily absorbed 

following inhalation exposure and metabolized to acetaldehyde and glutathione conjugates (Fedtke et al. 

1994a, 1994b). Additional quantitative studies of the pharmacokinetics of chloroethane are needed. 
CHLOROETHANE 87 

2. HEALTH EFFECTS 

Comparative Toxicokinetics. A study that compares the metabolism of chloroethane in rats and 

miceindicates that mice have a greater capacity to metabolize chloroethane than rats (Fedtke et al. 1994a, 

1994b). An in vitro study using human liver preparations to study the metabolism of chloroethane is 

needed to determine which species is the most appropriate model for the metabolism of chloroethane. 

Methods for Reducing Toxic Effects. Other than removing the subject from exposure 

(Haddad and Winchester 1990) and increasing ventilation rate to enhance elimination after the subject is 

removed from exposure, methods for reducing toxic effects were not identified. As more information is 

learned regarding the mechanism of chloroethane toxicity, methods for reducing the toxic effects of 

chloroethane can be developed. 

Children’s Susceptibility. No studies involving exposure of children or immature animals to 

chloroethane have provided quantitative doses. There are two very qualitative studies in children 

associated with the use of chloroethane as an anesthetic (Nielsen 1980; Noble 1979). There currently 

exists a need for studies with children or immature animals exposed to the compound to investigate any 

differences in dose absorption, metabolism, excretion, and presence and severity of effects, Current 

knowledge of differences in physiology and biochemistry between children and adults indicate that 

distribution and metabolism mightdiffer between children and adults. However, experiments evaluating 

qualitative and quantitative differences in these processes would greatly facilitate the understanding of 

adverse effects of chloroethane in the developing human. 

Definitive studies do not exist evaluating whether pharmacokinetics of chloroethane are different in 

children as compared with adults. Furthermore, no PBPK models exist on any age of children or adults 

that might inform the public as to the pharmacokinetics of the compound. 

Studies are needed to determine whether chloroethane or its metabolites cross the placenta and no studies 

have evaluated placental or cord blood concentrations of chloroethane or its metabolites in humans or 

animals. It is unknown whether the delayed bone development seen in the Scortichini et al. (1986) study 

was due to chloroethane or its metabolites crossing the placenta or to some indirect effect on the fetus. 

Experiments evaluating these parameters are needed, as well as experiments to determine whether 

chloroethane significantly accumulates in breast milk. One study detected the compound in breast milk 

(Pellizari et al, 1982), but neither route of exposure of the mother nor concentration of chloroethane in the 

milk was identified. In addition, studies determining whether chloroethane would be stored in maternal 
CHLOROETHANE 88 

2. HEALTH EFFECTS 

tissues would be informative, although the volatility of the compound, as well as data indicating its rapid 

clearance from the body following inhalation exposure (Morgan et al. 1970), indicate that tissue storage is 

not expected. 

Adequate data do not exist on the effect, if any, chloroethane exposure has on fetal development. The one 

available prenatal developmental study and data needs on this topic are discussed above in the 

Developmental Effects subsection. Reliable studies of this type are needed in determining the fetotoxicity 

of chloroethane, as well as the potential of the compound for disrupting normal child development. Studies 

on postnatal exposures and their influence on development in immature animals would also be useful. 

Child health data needs relating to exposure are discussed in 5.8.1 Data Needs: Exposures of Children. 

Data Needs for Modeling 

Studies which provide information on the physiological biochemical parameters specific to chloroethane 

in human and animal tissues are needed. For instance, there are no data on organ volumes, alveolar 

ventilation,cardiac output, or organ perfusion rates, among other parameters, in humans and animals. A 

PBPK model in rats exposed to chloroethane via inhalation was developed with the assumption that 

metabolism of the compound occurred exclusively in the liver (Gargas et al. 1990). The authors 

determined a Vmaxc which is the maximum velocity (Vmax) scaled for a 1 -kg animal, the Km (rate constant 

for the saturable pathway), and the first-order rate constant, Kfc, which is the rate constant (Kf) scaled for a 

l-kg animal. 

Other biochemical parameters that affect metabolism and clearance have not been investigated. Waller et 

al. ( 1996) modeled the cytochrome P450-mediated metabolism of chloroethane using three-dimensional 

quantitative structure-activity relationships (3D-QSAR). Their models have predicted a metabolic 

clearance rate for chloroethane. Other studies, involving the experimental or modeled estimation of other 

biochemical parameters, such as excretory clearance, binding and reactivity, absorption constants, 

inhibition rate constants, first pass effects, and other parameters that may influence the rate of elimination 

and bioavailability were not available. Studies investigating these parameters using human or animal 

tissues would provide much-needed information concerning the metabolism of chloroethane. 
CHLOROETHANE 89 

2. HEALTH EFFECTS 

2.11.3 Ongoing Studies 

Ongoing studies regarding chloroethane were not identified in the CRISP (1996), FEDRIP (1998), or 

CRIS/USDA (1998) databases. 

CHLOROETHANE 91 

3. CHEMICAL AND PHYSICAL INFORMATION 

3.1 CHEMICAL IDENTITY 

Information regarding the chemical identity of chhloroethane is located in Table 3-l. 

3.2 PHYSICAL AND CHEMICAL PROPERTIES 

Information regarding the physical and chemical properties of chloroethane is located in Table 3-2. 



CHLOROETHANE 95 

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

4.1 PRODUCTION 

Table 4-l lists the facilities in each state that manufacture or process chloroethane, the intended use, and 

the range of maximum amounts of chloroethane that are stored on site. There are currently 50 facilities 

that produce or process chloroethane in the United States. The data listed in Table 4-l are derived from 

theToxics Release Inventory (TRI) (TR196 1998). Only certain types of facilities were required to report. 

Therefore, this is not an exhaustive list. 

The production of chloroethane in the United States has decreased as the use of leaded gasoline has been 

regulated. In 1960, approximately 247,000 metric tons (1 metric ton = 1,000 kg) of chloroethane were 

produced, while in 1988 production of chloroethane was approximately 69,000 metric tons (IARC 1991). 

Companies on the TRI listed as producers of chloroethane include: Degussa Corporation and Huls 

America, Inc., in Theodore, AL; Monsanto Company in Muscatine, IA, and Bridgeport, NJ; Westlake 

Monomers Corporation in Calvert City, KY; BASF Corporation in Geismar, LA; Condea Vista Company 

in Westlake, LA; Dow Chemical Company in Plaquemine, LA, and Freeport, TX; Formosa Plastics 

Corporation in Baton Rouge, LA, and Point Comfort, TX; Georgia Gulf Corporation in Plaquemine, LA; 

PPG Industries in Lake Charles, LA; Vulcan Materials Company in Geismar, LA; Dow Chemical USA in 

Midland, MI; Dow Corning Corporation in Midland, MI; Akzo Nobel Chemicals, Inc., in Edison, NJ; 

Cyanamid Agricultural in Manati, PR; Lobeco Prods., Inc., in Lobeco, SC; Zeneca Specialties in Mount 

Pleasant, TN; Eastman Chemical Company in Longview, TX; Hoechst-Celanese in Bay City, TX; 

Occidental Chemical Corporation in Deer Park, TX, and Gregory, TX; Specialtychem Prods. Corporation 

in Marinette, WI; and OS1 Specialties, Inc., in Friendly, WV (TR196 1998). 

4.2 IMPORT/EXPORT 

From 1979 to 1988, chloroethane imports were significant only in 1980, 1981, and 1982. During those 

years, imported quantities were 1,270,5,030, and 2,325 metric tons, respectively (IARC 1991). From 1990 

to 1994, US. imports of chloroethane in kilograms were 3,011,432 in 1990,4,103,072 in 1991, 14,260 in 

1992,24 in 1993, and 0 in 1994 (NTDB 1996). 

CHLOROETHANE 97 

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

From 1979 to 1988, the United States exported 8,562-13,868 metric tons, with the maximum occurring in 

1986 and the minimum occurring in 1988 (IARC 1991). From 1991 to 1995, U.S. exports of chloroethane 

in metric tons were 11.3 in 1991, 16.8 in 1992, 15.1 in 1993,38.1 in 1994, and 5.4 in 1995 (NTDB 1996). 

4.3 USE 

In the past, the single largest use of chloroethane was in the production of tetraethyl lead. As recently as 

1984, 80% of the chloroethane consumed in the United States was used in domestic production of 

tetraethyl lead, 15% was used in the production of ethyl cellulose, and 5% was used for miscellaneous 

applications including use as a solvent, refrigerant, and topical anesthetic, and use in the manufacture of 

dyes, chemicals, and pharmaceuticals (HSDB 1997; Morris and Tasto 1979). Government-mandated 

reduction in the amount of lead additives used in gasoline in the United States and a shift to the use of 

unleaded gasoline caused a drastic reduction in the amount of chloroethane required for the production of 

tetraethyl lead (CMR 1982; EPA 1985; IARC 1991). 

Chloroethane has been used as a pulp vitality tester in dentistry, as a medication to alleviate pain 

associated with insect bums, stings, and sports injuries, as an adjunct in the treatment of tinea lesions and 

creeping eruptions, as a test for regional anesthesia before Caesarean section, and as a counterirritant and 

anesthetic for relief of myofacial and visceral pain syndromes (Adriani 1986; Boume et al. 1997; Brown 

1972; Ehrmann 1977; Marbach 1996; Ott 1969). Chloroethane has recently been used as a freezing agent 

to relieve spasms in recipient arteries in microvascular transfer (Cavadas 1996). 

Chloroethane is also used as a recreational inhalant, desired for its narcotic effects. The compound is 

manufactured in pressurized canisters and sold specifically for inhalant abuse under names such as Ethyl 

Gaz, Ethyl Four Star, Black Jac, and Maximum Impact (Hersh 199 1; Walker 1993). 

4.4 DISPOSAL 

Chloroethane is listed as a toxic substance under Section 3 13 of the Emergency Planning and Community 

Right to Know Act (EPCRA) under Title III of the Superfund Amendments and Reauthorization Act 

(SARA) (EPA 1998c). Disposal of wastes containing chloroethane is controlled by a number of federal 

regulations (see Chapter 7). 
CHLOROETHANE 98 

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

Chloroethane may be disposed of by controlled incineration. It is recommended that chloroethane be 

mixed with another combustible fuel prior to incineration; however, sufficient oxygen and an adequate 

operating temperature are mandatory to avoid incomplete combustion resulting in the formation of 

phosgene. Incinerators for this compound are typically equipped with an acid scrubber to remove halo 

acids from the effluent gas (HSDB 1997; OHM/TADS 1998). In a study of the thermal destruction of 

chloroethane, the minimum temperature required for 99.99% destruction with a 1 -second residence time 

was 727 °C (Fisher and Koshland 1990). Among the chlorinated methanes and ethanes studied, 

chloroethane had the lowest temperature required for destruction. Chloroethane is also a constituent of 

some waste-water streams; it is susceptible to removal by air stripping (HSDB 1997). Placing chloroethane 

in a landfill is not recommended (HSDB 1997). 
CHLOROETHANE 99 

5. POTENTIAL FOR HUMAN EXPOSURE 

5.1 OVERVIEW 

Chloroethane has been ientified in at least 282 of the 1,467 current or former EPA National Priorities List 

(NPL) hazardous waste sites (HazDat 1998). However, the number of sites evaluated for chloroethane is 

not known. The frequency of these sites within the United States can be seen in Figure 5-1. 

Chloroethane is a compound that occurs in the euviroument as the result of anthropogenic activity. 

Sources of chloroethane exposure include process and fugitive emissions from its production and use as a 

chemical intermediate; evaporation from waste-water streams, landfills, solvents, refrigerants, and 

anesthetics; emissions from plastics, refuse, and biomass combustion; formation during water chlorination; 

formation via anaerobic biodegradation of some chlorinated solvents; and evaporation and leaching from 

landfills. Most chloroethane released in the environment eventually enters the atmosphere. 

When released to the atmosphere, the dominant removal mechanism is expected to be reaction with 

photochemically-generated hydroxyl radicals (half-life of 40 days). Potential exists for removal from the 

atmosphere in precipitation; however, most chloroethane removed by this mechanism is likely to reenter 

the atmosphere by volatilization. When released to surface water, volatilization is expected to be the 

primary fate process (half-life of 2.4 hours in a model river). When released to soil, chloroethane either 

volatilizes rapidly from soil surfaces or leaches through subsurface soil where it becomes a potential 

groundwater contaminant. In groundwater, chloroethane would probably be subject to chemical 

hydrolysis. Sufficient data are not available to establish the rate of chloroethane degradation in 

groundwater. 

The general population may be exposed to low (ppt) levels of chloroethane through inhalation of 

contaminated ambient air and consumption of contaminated drinking water. Dermal contact can occur as a 

result of the intentional use of chloroethane as a topical anesthetic. Occupational exposure may occur by 

inhalation and/or dermal contact. According to a 1981-1983 NIOSH survey, an estimated 49,212 workers 

in the United States are potentially exposed to chloroethane in the workplace (NIOSH 1991). 

CHLOROETHANE 101 

5. POTENTIAL FOR HUMAN EXPOSURE 

5.2 RELEASES TO THE ENVIRONMENT 

According to the Toxics Release Inventory (TRI), in 1996, a total of 3,242,710 pounds (1,470,617 kg) of 

chloroethane was released to the environment from 50 large processing facilities (TR196 1998). Table 5-l 

lists amounts released from these facilities. In addition, an estimated 762 pounds (346 kg) were released 

by manufacturing and processing facilities to publicly owned treatment works (POTWs) and an estimated 

688,311 pounds (312,159 kg) were transferred offsite (TR196 1998). The TRI data should be used with 

caution because only certain types of facilities are required to report. This is not an exhaustive list. 

Chloroethane has been identified in a variety of environmental media (air, surface water, groundwater, 

soil, and sediment) collected at 282 of the 1,467 NPL hazardous waste sites. 

5.2.1 Air 

According to the Toxics Release Inventory (TRI), in 1996, the estimated releases of chloroethane of 

2553,260 pounds (1,157,941 kg) to air from 50 large processing facilities accounted for about 79% of total 

environmental releases (TR196 1998). Table 5-1 lists amounts released from these facilities. The TRI data 

should be used with caution because only certain types of facilities are required to report. This is not an 

exhaustive list. 

Chloroethane may be released to the environment through process and fugitive emissions related to its 

production and use as a chemical intermediate; through evaporative losses from waste-water streams, 

landfills, solvents, refrigerants, and anesthetics; and through emissions from combustion of plastics, 

refuse, and biomass (Graedel et al. 1986; Liepins et al. 1977; Vogt and Walsh 1985; Young and Parker 

1984). Based on 1980 air monitoring data, it was estimated that 20 million pounds of chloroethane per 

year were being released into the atmosphere in the United States (Singh et al. 1981). Between 1980 and 

1988, production levels of chloroethane in the United States decreased by approximately 62% (IARC 

1991), and a proportional decrease in emissions related to its production and use as a chemical 

intermediate probably occurred. 

CHLOROETHANE 103 

5. POTENTIAL FOR HUMAN EXPOSURE 

5.2.2 Water 

According to the Toxics Release Inventory (TRI), in 1996, the estimated releases of chloroethane of 

285 pounds (129 kg) to water from 50 large processing facilities accounted for about 0.01% of total 

environmental releases (TR196 1998). Table 5-l lists amounts released from these facilities. The TRI data 

should be used with caution because only certain types of facilities are required to report. This is not an 

exhaustive list. 

Limited data are available regarding the release of chloroethane to water. This compound may be released 

to the environment as a constituent of waste-water streams from various industries, particularly those that 

use chloroethane as an intermediate. The following industries have been identified as potential sources of 

release of chloroethane: electroplating, organic chemicals, steam electric, asbestos, timber products 

processing, metal finishing, paving and roofing, paint and ink formulating, gum and wood, and carbon 

black (EPA 1988a). It is possible that chloroethane forms in some waste-water streams as a result of 

disinfection bychlorination (Gould et al. 1983; Liepins et al. 1977; Otson 1987). Because of its volatility, 

the majority of chloroethane released to surface water is expected to enter the atmosphere. This compound 

can leach into groundwater from waste disposal sites, and it may form in groundwater as an anaerobic 

biodegradation product of chlorinated solvents (e.g., 1,l ,l -trichloroethane and cis-1 ,1 -dichloroethylene) 

(Barrio-Lage et al. 1986; Vogel and McCarty 1987). 

5.2.3 Soil 

According to the Toxics Release Inventory (TRI), in 1996, there were no releases to soil from the 50 large 

processing facilities required to report (TR196 1998). 

Chloroethane can occur in soil as a result of the disposal of waste products that contain this compound and 

as a result of formation as an anaerobic biodegradation product of various chlorinated compounds (e.g., 1 

,l ,ltrichloroethane and cis- 1,2-dichloroethylene) (Barrio-Lage et al. 1986; Vogel and McCarty 1987). 
CHLOROETHANE 104 

5. POTENTIAL FOR HUMAN EXPOSURE 

5.3 ENVIRONMENTAL FATE 

5.3.1 Transport and Partitioning 

The relatively high water solubility of chloroethane suggests that potential exists for removal of this 

compound from the atmosphere via washout. However, most chloroethane removed by this mechanism is 

likely to reenter the atmosphere by volatilization. 

The dominant removal process for chloroethane in surface water is expected to be volatilization. Based on 

a measured Henry’s Law constant of 1 .11x10-2 atm-m3

/mole at 24.8 °C, the volatilization half-life of 

chloroethane from a model river 1 m deep, flowing 1 m/second with a wind speed of 3 m/second was 

estimated to be 2.4 hours (Gessett 1987; Thomas 1982). 

Bioconcentration factors (BCF) of 7 and 5 have been estimated for chloroethane using linear regression 

equations based on a log of the octanol-water partition coefficient (Kow) of 1.43 and a water solubility of 

5,678 mg/L at 20°C, respectively (Bysshe 1982; Hansch and Leo 1985; Horvath 1982). These BCF values 

indicate that this compound would not bioconcentrate significantly in aquatic organisms. 

Adsorption coefficients (Koc) of 143 and 33 were estimated for chloroethane using linear regression 

equations based on log Kow and water solubility data, respectively (Lyman 1982). These &, values suggest 

that adsorption of chloroethane to suspended solids and sediments in water would not be a significant fate 

process. 

The likely insignificant sorption of chloroethane to soil, indicated by the relatively low Koc value for the 

compound, suggests that it would be highly mobile in soil and might undergo significant leaching (Swann 

et al. 1983). The relatively high vapor pressure of chloroethane and its volatility from water suggest that it 

would evaporate rapidly from soil surfaces, and that volatilization would probably be a major removal 

process. Washington (1996) has calculated a Kc value for chloroethane. This value is the ratio of the 

concentration of the compound in the gas phase relative to the water phase and indicates the mobility of 

the compound from water in saturated soils to vapor. The calculated value of Kc, 0.347 at 17.5 °C, 

indicates that chloroethane in soil has a propensity to become dissolved in soil water and will then enter 

soil gas. The concentrations of chloroethane in soil water and the vapor phase will approach equilibrium 

(Washington 1996). 
CHLOROETHANE 105 

5. POTENTIAL FOR HUMAN EXPOSURE 

5.3.2 Transformation and Degradation 

5.3.2.1 Air 

The dominant atmospheric removal process for chloroethane is predicted to be removal by reaction with 

photochemically-generated hydroxyl radicals in the troposphere. This reaction is believed to proceed via 

hydrogen abstraction (Atkinson 1985; Howard and Evenson 1976). The half-life for this reaction has been 

estimated to be 40 days based on a reaction rate constant of 4.0x10-13

 m

3

/molecule-second at 25 °C and a 

typical hydroxyl radical concentration of 5.0x105

 molecules/m3 (Atkinson 1985; Howard and Evenson 

1976). This tropospheric half-life suggests that less than 1% of the chloroethane released to the 

atmosphere would diffuse into the stratosphere, where it would be destroyed by photolysis (Callahan et al. 

1979). Chloroethane is not expected to photolyze in the atmosphere below the ozone layer since it contains 

no chromophores that absorb light in the visible part of the spectrum (wavelengths about 400-700 nm) 

(Hubrich and Stuhl l980; Jaffe and Orchin 1962; Mabey et al. 1981). 

5.3.2.2 Water 

Chloroethane is susceptible to slow chemical hydrolysis and forms ethanol and hydrochloric acid as 

reaction products. The hydrochloric acid formed dissociates at the neutral pH of most natural waters and 

forms a chloride salt. The hydrolytic half-life of chloroethane is not known with certainty. The hydrolytic 

half-life in water at 25 °C and pH 7 was estimated to be 38 days based on a reaction rate constant 

extrapolated from experimental data at 100°C (Laughton and Robertson 1959; Mabey and Mill 1978). 

However, in another study, the hydrolytic half-life was estimated to be approximately 1.9 years based on 

an estimated first-order rate constant of 1 .18x10m-8

 s

-1 obtained from the analysis of chloroethane in a 

batch fermented at 20°C (Vogel and McCarty 1987). Both the neutral and alkaline reaction rates for the 

hydrolysis of chloroethane were determined by Jeffers and Wolf (1996). The neutral reaction measured in 

0.01 M hydrochloric acid at 25 °C was found to predominate, with a rate constant of 5.1 x 10-7, resulting in 

an estimated half-life for chloroethane of 2.6 years. Despite these conflicting data, chemical hydrolysis 

may be an important fate process in groundwater when losses from other degradation and transport 

processes are expected to be negligible. 

The high volatility of chloroethane indicates that this compound will volatilize from groundwater and enter 

soil as a gas. In addition, chloroethane is susceptible to biodegradation in groundwater and other media. 

Vogel and McCarty (1987) have shown that chloroethane, formed by the anaerobic biodegradation of 
CHLOROETHANE 106 

5. POTENTIAL FOR HUMAN EXPOSURE 

trichloroethylene in a batch fermenter, was further dechlorinated by methanogenic bacteria. This study, 

however, provided no rate constant for this reaction that could be compared to the rate for hydrolysis. 

Oxidation of chloroethane in water via reaction with singlet oxygen or peroxy radicals is too slow to be 

environmentally relevant (Mabey et al. 198 1). Direct photolysis in surface waters is not expected to be an 

environmentally relevant fate process (Mabey et al 1981). 

5.3.2.3 Sediment and Soil 

In moist subsurface soils, chloroethane is expected to be susceptible to chemical hydrolysis. However, this 

pathway is expected to be slow and other fate and transport processes may predominate. A large body of 

data exists on the biodegradation of chlorinated alkenes and alkanes under anaerobic or aerobic conditions. 

The majority of this data, however, deals with polycblorinated compounds that are biodegraded to 

chloroethane or a structurally similar alkane or alkene (Ahlert and Enzminger 1992; Barrio-Lage et al. 

1986; Chang and Alvarez-Cohen 1996; Tabak et al. I98 1; Vogel and McCarty 1987). 

Chloroethane can undergo reductive dehalogenation by methanogenic bacteria in an anaerobic cell 

suspension or packed column environment (Baek et al. 1990; Holliger et al. 1990). Ethane and 

hydrochloric acid are formed by the reductive dechlorination of chloroethane (Holliger et al. 1990). In 

addition, chloroethane can be oxidized by aerobic nitrifying bacteria (Rasche et al. 1990). Both 

acetaldehyde and 2-chloroethanol are produced from the oxidation of chloroethane, with acetaldehyde 

predominating at more than 98% of the total product (Rasche et al. 1990). 

Although these studies provided maximum product formation rates, first-order rate constants were not 

estimated; therefore, no comparisons could be made to determine which biodegradation pathway would 

more rapidly clear chloroethane from a contaminated environment. The pathways do not directly compete, 

because they occur in different environments, one in an oxygen-deficient environment and the other in an 

oxygen-rich environment. For example, methanogenic environments are found at landfills and deep 

aquifers rich in carbohydrate-like compounds. Denitrifying environments are common to agricultural land 

use as well as areas that have on-site wastewater treatment systems (Ahlert and Enzminger 1992). 

Further, optimal biodegradation of chloroethane in aquifers or saturated sediments or soils is highly 

dependent on the presence of appropriate metabolizing bacteria, the migration of the contaminant to the 

bacteria, and the availability and concentration of necessary reactants such as carbon sources, reducers, 
CHLOROETHANE 107 

5. POTENTIAL FOR HUMAN EXPOSURE 

and/or oxidizers. While laboratory studies indicate that biodegradation can be a significant pathway for 

clearance of chloroethane and other contaminants from affected media, the importance of this pathway in 

the environment is still unknown. 

5.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT 

Reliable evaluation of the potential for human exposure to chloroethane depends in part on the reliability 

of supporting analytical data from environmental samples and biological specimens. In reviewing data on 

chloroethane 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. 

5.4.1 Air 

Limited data are available regarding the detection of chloroethane in air. Monitoring data from the early 

1980s indicate that levels of chloroethane in ambient air at various urban/suburban locations in the United 

States ranged from 10 to 1,248 ppt with average concentrations ranging from 41 to 140 ppt (Shepson et al. 

1987; Singh et al. 198 1). Marine air samples collected in the Northern Hemisphere during 198 1 contained 

an average concentration of 19 ppt (Singh et al. 1983). Rural air samples collected in 1974-1975 in the 

northwest United States contained less than 5 ppt chloroethane (Grimsrud and Rasmussen 1975). Current 

ambient levels of chloroethane are believed to be markedly lower than levels found during the mid 1970s 

and early 1980s because of a substantial decrease in the production of chloroethane in the United States. 

Chloroethane has been detected in the air samples of landfill gas collected from a municipal/industrial 

landfill in the United Kingdom and a municipal landfill simulator (Young and Parker 1984; Vogt and 

Walsh 1985). These data indicate that chloroethane may be found in the air above some landfills. 

However, sufficient data are not available to determine whether elevated levels of chloroethane typically 

occur at or in the vicinity of 

waste disposal sites. 

5.4.2 Water 

Limited data are available regarding the detection of chloroethane in surface water, groundwater, drinking 

water, and waste water. Analysis of data input into the EPA STORET database during the early 1980s 

indicates that chloroethane is not a common surface water pollutant and that levels in unfiltered surface 

water samples typically fall below the detection limit (<10 mg/L) (Staples et al. 1985). Chloroethane 
CHLOROETHANE 108 

5. POTENTIAL FOR HUMAN EXPOSURE 

contamination of groundwater has occurred at various waste disposal sites throughout the United States 

(ATSDR 1989,199l; Cline and Viste 1985; EPA 1986a, 1987; Myers 1983; Sabel and Clark 1984). 

Groundwater and landfill leachate were the media in which chloroethane was most frequently found at 

NPL hazardous waste sites (HazDat 1998). Chloroethane was found in groundwater at 218 sites and in 

leachate at 43 NPL sites. Results of a 1982-1983 survey of 10 Canadian drinking water supplies suggest 

that trace levels (<0.1 mg/L) of chloroethane may occur in some finished drinking water supplies as a 

result of formation during the chlorination process (Otson 1987). During the 1975 EPA National Organics 

Reconnaissance Survey (NORS), chloroethane was qualitatively identified in drinking water samples from 

three of five finished drinking water supplies in the United States (EPA 1975). Without more recent or 

comprehensive data, the average daily intake of chloroethane by ingestion of drinking water cannot be 

estimated. Chloroethane is not a common constituent of treated waste water (EPA 198 1; Perry et al. 1979; 

Staples et al. 1985; Young et al. 1983). The maximum reported concentration for chloroethane in a waste 

stream was 10 mg/L in treated waste water from a paint and ink formulation industry (EPA 1981). A 

survey of storm water runoff samples collected from 15 cities located across the United States revealed 

that chloroethane is not a typical contaminant of stormwater runoff (Cole et al. 1984). 

5.4.3 Sediment and Soil 

Chloroethane was found in sediment at 10 NPL sites and in soil at 42 NPL sites (HazDat 1998). In a 

survey of U.S. waste-water treatment plants receiving both municipal and industrial waste streams, 

chloroethane was found in undigested sewage sludge from 2 of 13 plants at concentrations ranging from 

14.5 to 24 mg/kg dry weight. Assuming that the sludge was disposed of by land application, the 

application rate of chloroethane to soil was projected to be 0.16-0.17 kg/hectare (dry weight), and the 

resulting concentration of chloroethane in the top 15 cm of soil was predicted to be 0.08-0.085 mg/kg 

(Naylor and Loehr 1982). 

5.4.4 Other Environmental Media 

Few reports are available concerning the identification of chloroethane in other media. Traces of 

chloroethane were found in two of eight human milk samples taken from women in four urban areas of the 

United States (Pellizzari et al. 1982). Chloroethane at a mean concentration of 7.6 ng/g was found in 

oysters collected from Lake Pontchartrain, LA (Ferrario et al. 1985). 
CHLOROETHANE 109 

5. POTENTIAL FOR HUMAN EXPOSURE 

5.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE 

According to a National Occupational Exposure Survey (NOES) conducted by NIOSH between 1981 and 

1983, an estimated 49,212 workers in the United States are potentially exposed to chloroethane (NIOSH 

1991). This was a tentative estimate and extrapolating to the present, such estimates are subject to change 

depending upon whether further information on trade name compounds containing chloroethane becomes 

available. Workers may be exposed to chloroethane by inhalation and/or dermal exposure. Chloroethane 

exposure can occur in several occupational environments including: chemical manufacturing industries; 

medical and health facilities; automotive dealerships and service stations; wholesale trade, electric, gas and 

sanitary services; companies manufacturing or using machinery (except electrical); metal production 

facilities; printing and publishing companies; paint manufacturers and painting companies; companies 

manufacturing rubber and plastic products not elsewhere classified; and companies manufacturing food 

and kindred products (Fidler et al. 1987; Parker et al. 1979). Workers who may potentially be exposed 

include physicians, nurses, and other medical workers, automobile mechanics, office machine mechanics, 

household appliance and accessory installers, assemblers, professional painters, heavy-equipment 

mechanics (including diesel mechanics), and plumbers and pipe fitters (Fidler et al. 1987; Parker et al. 

1979). Limited data indicate that the general population is exposed to very low (ppt) levels of chloroethane 

by inhalation of contaminated air and ingestion of contaminated drinking water. Apparently, people 

residing in urban/suburban areas are exposed to somewhat higher levels of chloroethane in air than people 

living in rural areas (Grimsrud and Rasmussen 1975; Shepson et al. 1987; Singh et al. 1983). Medical use 

of chloroethane as a topical anesthetic results in direct dermal exposure of the general population to this 

compound. The general population is also exposed to chloroethane by dermal contact with consumer 

products that contain this compound (i.e., various paints, solvents, refrigerants) (HSDB 1997). 

5.6 EXPOSURES OF CHILDREN 

This section focuses on exposures from conception to maturity at 18 years in humans and briefly considers 

potential pre-conception exposure to germ cells. Differences from adults in susceptibility to hazardous 

substances are discussed in 2.6 Children’s Susceptibility. 

Children are not small adults. A child’s exposure may differ from an adult’s exposure in many ways. 

Children drink more fluids, eat more food, and breathe more air per kilogram of body weight, and have a 

larger skin surface in proportion to their body volume. A child’s diet often differs from that of adults. The 
CHLOROETHANE 110 

5. POTENTIAL FOR HUMAN EXPOSURE 

developing humans 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; they put things in their mouths; they 

may ingest inappropriate things such as dirt or paint chips; they spend more time outdoors. Children also 

are closer to the ground, and they do not have the judgement of adults in avoiding hazards (NRC 1993). 

Children can be exposed inadvertently to chloroethane via household products such as paints, solvents, air 

fresheners, and refrigerants. However, children are unlikely to be exposed to a significant amount of 

chloroethane during normal use of these products by adults. Children can be exposed to chloroethane by 

intentionally sniffing household products containing the compound or sniffing packaged chloroethane that 

is sold specifically for misuse as an inhalant (Hersh 1991; Walker 1993). 

Children can also be exposed to chloroethane via contaminated drinking water or foods. Chloroethane 

concentrations in drinking water are expected to be low. One study was identified that reported 

chloroethane in small amounts (7.6 ng/g) in oysters in Lake Pontchartrain, LA (Ferrario et al. 1985). 

Because children drink more fluids and eat more food per kilogram of body weight than adults, they are 

expected to be disproportionately affected by exposure to chloroethane. However, because of the low 

concentrations of chloroethane detected in food and water, dietary exposures are not expected to be 

significant in children. 

Chloroethane has been detected in human breast milk (Pellizari et al. 1982). However, the concentrations 

of chloroethane were not determined, nor was the exposure dose. Therefore, it is not possible to determine 

how much of an absorbed chloroethane dose would be excreted in the milk and ingested by a nursing 

infant. In addition, the number of women with detectable levels of chloroethane in their milk was low; data 

do not exist that could indicate what percentage of an exposed female population could be expected to 

excrete chloroethane in their breast milk. 

Parents’ work clothes, skin, hair, tools, or other objects removed from the workplace are not likely to be a 

source of exposure to children. Chloroethane is a gas at room temperature and pressure; thus, it will not 

remain on parents’ clothes, hair, skin or other items, even for those who work with liquid chloroethane. 

Therefore, secondary exposure to children is unlikely. 

It is unknown whether children are different in their weight-adjusted intake of chloroethane. 
CHLOROETHANE 111 

5. POTENTIAL FOR HUMAN EXPOSURE 

5.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES 

Humans are typically exposed to very low levels of chloroethane. Nonetheless, potentially high levels 

could result from occupational exposure, exposure at or near hazardous waste sites, and frequent contact 

with consumer products that contain chloroethane (i.e., solvents, paints, refrigerants). Inhalation and 

dermal contact are expected to be the primary routes of exposure, although ingestion via indirect contact 

(e.g., eating foods that come in contact with contaminated surfaces or swallowing mucus that becomes 

contaminated as the result of breathing air containing chloroethane) is also possible. 

5.8 ADEQUACY OF THE DATABASE 

Section 104(I)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with the 

Administrator of EPA and agencies and programs of the Public Health Service) to assess whether adequate 

information on the health effects of chloroethane is available. Where adequate information is not available, 

ATSDR, in conjunction with the NTP, is required to assure the initiation of a program of research 

designed to determine the health effects (and techniques for developing methods to determine such health 

effects) of chloroethane. 

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. 

5.8.1 Identification of Data Needs 

Physical and Chemical Properties. Data on the physical and chemical properties of 

chloroethane are available (Budavari 1989; HSDB 1997). A Koc value provides a means for predicting 

whether a compound will partition significantly into suspended solids and sediments in water or adsorb 

strongly to soil. A Koc for chloroethane was estimated using regression equations based on log Kow and 

water solubility data (Lyman 1982). This estimation technique is believed to provide a reasonable 

approximation of Koc. However, additional studies are needed in which the soil adsorption coefficient of 

chloroethane is measured in order to remove any doubt concerning the reliability of the Koc. 
CHLOROETHANE 112 

5. POTENTIAL FOR HUMAN EXPOSURE 

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 chemical release and off-site transfer information to the EPA. The Toxics Release 

Inventory (TRI), which contains this information for 1996, became available in May of 1998. This 

database will be updated yearly and should provide a list of industrial production facilities and emissions. 

Data are adequate for the production and disposal of chloroethane (IARC 199 1; TR196 1998). 

Information on the pattern of use of chloroethane is not available after 1988. Information would have to be 

supplied by the chemical industry in order to establish the percentage breakdown of the current 

chloroethane uses. This type of information is needed to establish the sources of chloroethane release and 

the potential for general population and occupational exposure. 

Environmental Fate. Conflicting data are available concerning the hydrolytic half-life of 

chloroethane in water (Jeffers and Wolf 1996; Laughton and Robertson 1959; Mabey and Mill 1978; 

Vogel and McCarty 1987). Experimental data obtained from a hydrolysis study carried out in distilled 

water under environmental conditions (at 25 °C and pH 5-9) are needed to predict the half-life of 

chloroethane (Haider 1980; Kobayashi and Rittmann 1982) in natural water and moist soil. Available data 

regarding biodegradation of chloroethane are insufficient for predicting the importance of biodegradation 

as a removal process for chloroethane. Natural water grab sample biodegradation studies and soil 

metabolism studies carried out under both aerobic and anaerobic conditions are needed to estimate the 

biodegradation half-life of chloroethane. Although volatilization from soil is expected to be an important 

fate process (Washington 1996), data pertaining to the rate of volatilization from soil surfaces were not 

located in the available literature. Studies involving the measurement of the volatilization rate of 

chloroethane from soil surfaces are needed to evaluate the persistence of this compound upon release to 

soil. The dominant removal mechanism for chloroethane in air is expected to be reaction with 

photochemically-generated hydroxyl radicals (Atkinson 1985; Howard and Evenson 1976). However, no 

data are available concerning the products of this reaction. These data are needed to understand the 

mechanism by which this compound degrades in the atmosphere. 

Bioavailability from Environmental Media. Chloroethane is readily absorbed following 

inhalation exposure, the major route of exposure (Konietzto 1984; Lehman and Flury 1943; Torkelson and 

Rowe 1981). Data regarding the bioavailability of chloroethane from different media for other routes of 

exposure were not identified. Studies examining the absorption of chloroethane from various media 

following oral and dermal exposure are needed to predict exposure to chloroethane at hazardous waste 

sites. 
CHLOROETHANE 113 

5. POTENTIAL FOR HUMAN EXPOSURE 

Food Chain Bioaccumuiation. Based on bioconcentration factors of 7 and 5 estimated from log Kow 

and water solubility (Bysshe 1982; Hansch and Leo 1985; Horvath 1982), chloroethane is not expected to 

bioconcentrate significantly in aquatic organisms. Studies in which chloroethane is measured in biota and 

environmental media are needed to determine if the predictions are correct. 

Exposure Levels in Environmental Media. Relatively large amounts of chloroethane are released to 

the environment on an annual basis (TR196 1998). However, limited data were available concerning the 

detection of chloroethane in the environment, particularly in ambient air (Shepson et al. 1987; Singh et al. 

198 1), air in the vicinity of waste disposal sites (Vogt and Walsh 1985; Young and Parker 1984), drinking 

water, groundwater downgradient from waste disposal sites (HazDat 1998), and soil at waste disposal sites 

(HazDat 1998; Otson 1987). Reliable monitoring data for the levels of chloroethane in contaminated 

media at hazardous waste sites are needed so that the information obtained on levels of chloroethane in the 

environment can be used in combination with the known body burdens of chloroethane to assess the 

potential risk of adverse health effects in populations living in the vicinity of hazardous waste sites. 

Exposure Levels in Humans. Despite the fact that chloroethane is a fairly large volume commercial 

compound, limited data are available concerning occupational exposure. Tentative results of the National 

Occupational Exposure Survey are indicative of the number of workers potentially exposed to 

chloroethane in industry (NIOSH 1991). However, there are no quantitative data relating type of 

occupation to level and route of exposure. Available data indicate that the general population may be 

exposed to chloroethane by inhalation, ingestion of drinking water, and dermal contact (HSDB 1997). 

However, data were insufficient for estimating average daily intake by these routes. Up-to-date 

comprehensive monitoring data for air, water, and soil are needed to determine the typical amount of 

chloroethane to which the general population is exposed. 

This information is necessary for assessing the need to conduct health studies on these populations. 

Exposures of Children. Children are exposed to chloroethane via many different exposure pathways. 

However, to date no studies have provided information on adverse effects observed in children as a result 

of exposure to a specific dose of the compound. Reliable exposure and body burden studies in children are 

needed to relieve this data gap. In addition, because many older children may be exposed to chloroethane 

through sniffing the compound directly, there is a need to explore the prevalence of this behavior, the 

frequency of the abuse, and resulting exposure doses. 
CHLOROETHANE 114 

5. POTENTIAL FOR HUMAN EXPOSURE 

It is currently unknown whether children differ from adults in their weight-adjusted intake of chloroethane. 

Therefore, studies investigating this issue are needed. 

Exposure Registries. No exposure registries for chloroethane were located. This substance is not 

currently one of the compounds for which a subregistry has been established in the National Exposure 

Registry. The substance will be considered in the future when chemical selection is made for subregistries 

to be established. The information that is amassed in the National Exposure Registry facilitates the 

epidemiological research needed to assess adverse health outcomes that may be related to exposure to this 

substance. 

5.8.2 Ongoing Studies 

Ongoing studies regarding the environmental fate of chloroethane were not identified in the CRISP (1996), 

PEDRIP (1998), or CRIS/USDA (1998) databases. 
CHLOROETHANE 115 

6. ANALYTICAL METHODS 

The purpose of this chapter is to describe the analytical methods that are available for detecting, and/or 

measuring, and/or monitoring chloroethane, its metabolites, and other biomarkers of exposure and effect to 

chloroethane. The intent is not to provide an exhaustive list of analytical methods. Rather, the intention is 

to identify well-established methods that are used as the standard methods of analysis. Many of the 

analytical methods used for environmental samples are the methods approved by federal agencies and 

organizations such as EPA and the National Institute for Occupational Safety and Health (NIOSH). Other 

methods presented in this chapter are those that are approved by groups such as the Association of Official 

Analytical Chemists (AOAC) and the American Public Health Association (APHA). Additionally, 

analytical methods are included that modify previously used methods to obtain lower detection limits, 

and/or to improve accuracy and precision. 

6.1 BIOLOGICAL SAMPLES 

The analytical methods for the determination of chloroethane in biological matrices are given in Table 6-1. 

The purge and trap method used for environmental samples is also commonly used for biological samples. 

The discussion regarding the methods that may be most sensitive for determining chloroethane levels in 

environmental samples and the advantages and disadvantages of the commonly used methods as given in 

Section 6.2 are also applicable for biological samples. 

6.2 ENVIRONMENTAL SAMPLES 

Analytical methods for the determination of chloroethane in environmental samples are presented in 

Table 6-2. The two common methods used for preconcentrating chloroethane in air samples are adsorption 

on a sorbent column and collection in a cryogenically cooled trap. The disadvantages of cryogenic cooling 

are that the method is cumbersome and condensation of moisture in air may block the passage of further 

air through the trap. The disadvantages of the sorption tubes are that the sorption and desorption 

efficiencies may not be 100% and that the background impurities in the sorbent tubes may interfere with 

the detection of samples containing low concentrations of chloroethane (Cox 1983). The most common 

method for determining chloroethane levels in water, sediment, soil, and aqluatic species is purging 

chloroethane vapor from the sample or its solution in water using an inert gas and then trapping the 

desorbed vapors in a sorbent 





CHLOROETHANE 121 

6. ANALYTICAL METHODS 

trap. Subsequent thermal desorption is used for the quantification of its concentration. The two analytical 

instruments that provide the lowest detection limits are the halide-specific detectors (e.g., Hall electrolytic 

conductivity detector) and the mass spectrometer (see Table 6-2). The advantages of halide-specific 

detectors are that they are not only very sensitive, but they are also specific for halide compounds. The 

mass spectrometer, however, provides an additional confirmation of the presence of a compound through 

the ionization patterns and is desirable when a variety of compounds are to be quantified. High-resolution 

gas chromatography with capillary columns is a better method for volatile compounds than 

chromatography with packed columns because capillary columns provide better resolution of closely 

eluting compounds and increase the sensitivity of detection. In addition, purge and whole column 

cryotrapping eliminates the need for the conventional purge and trap unit and reduces the time of analysis 

(Pankow and Rosen 1988). The plugging of the trap by the condensation of moisture during cryotrapping 

may be avoided by using a wide bore capillary column, although the chromatographic resolution of such a 

column is inferior to narrow bore capillary columns (Mosesman et al. 1987; Pankow and Rosen 1988). 

6.3 ADEQUACY OF THE DATABASE 

Section 104(I)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with the 

Administrator of EPA and agencies and programs of the Public Health Service) to assess whether adequate 

information on the health effects of chloroethane is available. Where adequate information is not available, 

ATSDR, in conjunction with the NTP, is required to assure the initiation of a program of research 

designed to determine the health effects (and techniques for developing methods to determine such health 

effects) of chloroethane. 

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. 
CHLOROETHANE 122 

6. ANALYTICAL METHODS 

6.3.1 Identification of Data Needs 

Methods for Determining Parent Compounds and Metabolites in Biological Materials. 

There is a relative paucity of data on the analytical methods for the determination of chloroethane levels, 

as well as levels of its metabolites, in biological matrices. Most of the limited number of publications that 

discuss the methods for the determination of organic volatiles in biological matrices (Michael et al. 1989; 

Pellizzari et al. 1979) are not specific for chloroethane. These studies analyze other structurally-similar 

chlorinated hydrocarbons and discuss the applicability of the techniques for measuring other 

hydrocarbons. Therefore, it is believed that these techniques would be useful for the detection of 

chloroethane in certain biological matrices. However, recovery data and detection limits have not been 

conclusively determined for chloroethane at this time. Further studies to develop analytical methodologies 

for the determination of chloroethane in biological matrices are needed. 

One study was identified which described the assay of a chloroethane metabolite in human urine (ESkinja 

et al. 1997). This study measured the concentration of ethylmercapturic acid (EMA), a metabolite of 

glutathione conjugation of chloroethane, in urine from subjects presumably exposed to chloroethane. 

Themethod is fairly sensitive, with detection limits in the ppb range. 

Methods for Determining Biomarkers of Exposure and Effect. No known biomarker for this 

chemical in human tissue or body fluids has been identified. Ethylmercapturic acid, a metabolite of 

glutathione conjugation of chloroethane, can be detected in human urine. However, this metabolite can be 

formed by glutathione conjugation to other structurally-similar compounds and is not specific to 

chloroethane exposure. The potential usefulness of this compound as an indicator of exposure needs to be 

investigated further. Additional studies to identify specific biomarkers and to develop analytical 

monitoring methodologies for the determination of chloroethane exposure are needed. One breath 

absorption study using inhaled radiolabeled chloroethane quantitatively measured absorption of the 

compound (Morgan et al. 1970). However, the analytical technique used is not applicable for widespread 

use because it involved quantitative analysis of the radiolabel, not the compound itself. 
CHLOROETHANE 123 

6. ANALYTICAL METHODS 

Methods for Determining Parent Compounds and Degradation Products in 

Environmental Media. Analytical methods with adequate sensitivity and specificity are available 

for the quantification of chloroethane in environmental samples (Driscoll et al. 1987; EPA 1982a, 1986b; 

Ferrario et al. 1985; Hiatt 1983; Lopez-Avila et al. 1987; Otson and Ghan 1987; Shepson et al. 1987; Vogt 

and Walsh 1985). The degradation products of chloroethane are ethanol and chloride salts (the 

hydrochloric acid initially formed dissociates to form chloride salts at the neutral pH values in most 

environmental media). Analysis for these compounds in environmental media would provide little or no 

information about chloroethane. 

6.3.2 Ongoing Studies 

No significant ongoing studies are in progress for the development of analytical methodologies for 

chloroethane and its metabolites in biological media or for chloroethane and its degradation products in 

environmental media. 

CHLOROETHANE 125 

7. REGULATIONS AND ADVISORIES
 

The international, national, and state regulations and guidelines regarding chloroethane in air and water are 

summarized in Table 7-l. 

IARC considers chloroethane to be a Group 3 carcinogen, not classifiable (IARC 1991). A carcinogenic 

assessment of chloroethane has not been completed by the EPA (IRIS 1997). ACGIH considers 

chloroethane to be an animal carcinogen of unknown relevance to humans (ACGIH 1998). 

Toxicity data for chloroethane are limited to inhalation data. Therefore, estimates of safe exposure 

concentrations are only available for air. The QSHA permissible exposure limit (PEL) for chloroethane is 

1,000 ppm (OSHA 1998). ACGIH recommends an occupational exposure threshold limit value 

timeweighted average (TLV-TWA) of 100 ppm (skin) (ACGIH 1998). 

ATSDR has derived an acute-duration inhalation MRL of 15 ppm with an uncertainty factor of 100, based 

on a NOAEL of 1,504 ppm for fetotoxicity in mice that was observed at 4,946 ppm (Scortichini et al. 

1986). The EPA reference concentration (RfC) of 10 mg/m3

 (4 ppm) is based on the same study. EPA used 

uncertainty factors of 10 to account for sensitive populations, 3 for interspecies extrapolation with 

dosimetric adjustment of the inhaled concentration, and 10 for database deficiencies (the lack of a 

multigeneration study). 



CHLOROETHANE 129 

8. REFERENCES
 

ACGIH. 1991. Documentation of the threshold limit values and biological exposure indices. 6th edition. 

American Conference of Governmental Industrial Hygienists. Cincinnati, OH. 

*ACGIH. 1998. TLVs and BEIs: Threshold limit values for chemical substances and physical 

agents-Biological exposure indices. American Conference of Governmental Industrial Hygienists. 

Cincinnati, OH. 37. 

*Adinolfi M. 1985. The development of the human blood-csf-brain barrier. Dev Med Child Neurol 

27:532-537. 

*Adriani J. 1941. The pharmacology of anesthetic drugs. Springfield, IL: Thomas, 33-34. 

*Adriani J. 1986. Selection of anesthesia. Int Anesthesiol Clin 6:96 I - 1040. 

*Ahlert RC, Enzminger JD. 1992. Anaerobic processes for the dechlorination of 1, I, 1 -trichloroethane. J 

Environ Sci Health A27: 1675- 1699. 

*Altman PK, Dittmer DS. 1974. Biological handbooks: Biology data book. Volume III, 2nd ed. Bethesda, 

MD: Federation of American Societies for Experimental Biology, 1987-2008,204l. 

*Amdur MO, Doull J, Klaassen CD, eds. 199 1. Casarett and Doull’s toxicology: The basic science of 

poisons. 4th ed. New York, NY: Pergamon Press, 108. 

*Amoore JE, Hautala E. 1983. Odor as an aid to chemical safety: Odor thresholds compared with 

threshold limit values and volatilities for 214 industrial chemicals in air and water dilution. J Appl Toxico1 

3:272-290. 

*Andersen ME, Krishnan K. 1994. Relating in vitro to in vivo exposures with physiologically-based tissue 

dosimetry and tissue response models. In: Salem H, ed. Animal test alternatives. Aberdeen Proving 

Ground, Maryland: U.S. Army Chemical Research Development and Engineering Center. 

*Andersen ME, Clewell HJ,III, Gargas ML, et al. 1987. Physiologically based pharmacokinetics and the 

risk assessment process for methylene chloride. Toxicol Appl Pharmacol 87: 185-205. 

*Atkinson R. 1985. Kinetics and mechanisms of the gas-phase reactions of hydroxyl radical with organic 

compounds under atmospheric conditions. Chem Rev 85:69-201. 

*ATSDR. 1989. Decision guide for identifying substance-specific data needs related to toxicological 

profiles. Agency for Toxic Substances and Disease Registry, Division of Toxicology, Atlanta, GA. 

*ATSDR. 199 1. Health assessment for Beacon Heights Landfill Site, Beacon Falls, Connecticut, Region 

1. Cerclis No. CTD072122062. Addendum. Agency for Toxic Substances and Disease 

Registry.PB91205666. 

*Cited in text 
CHLOROETHANE 130 

8. REFERENCES 

*ATSDIUCDC. 1990. Subcommittee report on biological indicators of organ damage. Agency for Toxic 

Substances and Disease Registry, Centers for Disease Control and Prevention, Atlanta, GA. 

*Baek NH, Jaffe PR, Shingal N. 1990. Simulating the degradation of TCE under methanogenesis. J 

Environ Sci Health A25:987-1005. 

*Balasubramanian D, Wetlaufer DB. 1966. Reversible alteration of the structure of globular proteins by 

anesthetic agents. Proc Nat1 Acad Sci USA 55:762-765. 

*Barnes DG, Dourson M. 1988. Reference dose (RfD): Description and use in health risk assessments. 

U.S. Environmental Protection Agency. Regul Toxicol Pharmacol8:47 l-486. 

*Barrio-Lage G, Parsons FZ, Nassar RS, et al. 1986. Sequential dehalogenation of chlorinated ethenes. 

Environ Sci Technol 20:96-99. 

*Benowitz NL. 1992. Hazardous materials toxicity: Clinical principles of environmental health. In: 

Sullivan JB, Krieger GR, eds. Cardiac toxicity. Baltimore, MD: Williams & Wilkins, 168178. 

*Bircher AJ, Hampl K, Hirsbrunner P, et al. 1994. Allergic contact dermatitis from ethyl chloride and 

sensitization to dichlorodifluoromethane. Contact Dermatitis 31:41-44. 

*Bos SD, Buys GA. 1994. Treatment of priapism with ethyl chloride spray after failed intracavernous 

injection with adrenaline. Br J Urol 74:677-678. 

*Bourne TM, deMelo AE, Bastianpillai BA, et al. 1997. A survey of how British obstetric anaesthetists 

test regional anaesthesia before Caesarean section. Anaesthesia 52:896-913. 

*Bronstein AC, Currance PL. 1988. Emergency care for hazardous materials exposure. St. Louis, MO: 

The C.V. Mosby Company, 143- 144. 

*Brown BR Jr. 1972. Office management of common musculoskeletal pain syndromes. Am Fam 

Physician 6:92-98. 

*Bucher JR Morgan DL, Adkins B Jr, et al. 1995. Early changes in sex hormones are not evident in mice 

exposed to ;he uterine carcinogens chloroethane or bromoethane. Toxicol Appl Pharmacol 130: 169-l 73. 

*Budavari S, O’Neil MJ, Smith A, et al., eds. 1989. The Merck Index: An encyclopedia of chemicals, 

drugs, and biologicals. Eleventh edition. Rahway, NJ: Merck & Co., Inc., 597. 

*Bush OF, Bittenbender G, Adriani J. 1952. Electrocardiographic changes during ethyl chloride and vinyl 

ether anesthesia in the dog and man. Anesthesiology 13: 197-202. 

*Bysshe SE. 1982. Bioconcentration factors in aquatic organisms. In: Lyman WJ, Reehl WF, Rosenblatt 

DH, eds. Handbook of chemical property estimation methods. New York: McGraw-Hill Book Co., 

Chapter 5. 

*Callahan MA, Slimak MW, Gavel NW, et al. 1979. Water-related environmental fate of 129 priority 

pollutants. Vol. II. EPA-440/4-79-029B. U.S. EPA Office of Water Planning and Standards, Washington, 

DC, 42-l to 42-49. 
CHLOROETHANE 131 

8. REFERENCES 

*Cavadas PC. 1996. In viva vascular freezing in clinical microvascular transfer. Microsurgery 17: 121-2.
 

*Chang HL, Alvarez-Cohen L. 1996. Biodegradation of individual and multiple chlorinated aliphatic
 

hydrocarbons by methane-oxidizing cultures. Appl Environ Microbial 62:337 1-3377.
 

C&EN. 1988. Production by the U.S. chemical industry. Chemical and Engineering News, June 20, 1988,
 

40. 

*Clewell HJ, III, Andersen ME. 1985. Risk assessment extrapolations and physiological modeling.
 

Toxico1 IndHealth 1:111-113.
 

*Cline PV, Viste DR. 1985. Migration and degradation patterns of volatile organic compounds. Waste
 

Management Research 3:35 I-360.
 

*CMR. 1982. Chemical profile: Ethyl chloride. Chemical Marketing Reporter. August 2, 1982.
 

*Cole RH, Frederick RE, Healy RP, et al. 1984. Preliminary findings of the priority pollutant monitoring
 

project of the Nationwide Urban Runoff Program. J Water Pollut Control Fed 56:898-908.
 

*Cole WH. 1956. Ethyl chloride as a gaseous anesthetic. Anesthesia 11:156-l 59.
 

*Cole WH. 1967. A re-evaluation of the pharmacology of ethyl chloride. Med J Aust 1:853-855.
 

*Cox RD. 1983. Sample collection and analytical techniques for volatile organics in air. Special
 

Conference on Measurement and Monitoring of Non-Criteria (Toxic) Contamination in Air,
 

Knickerbocker Hotel, Chicago, IL, March 22-24, 1983. Chicago, IL: Air Pollution Conrol Association,
 

10l- 112.
 

*CRIS/USDA. 1998. Current Research Information System/United States Department of Agriculture.
 

Beltsville, MD. May 13, 1998.
 

*CRISP. 1996. Computer Retrieval of Information on Science Projects. National Library of Medicine,
 

National Institutes of Health, Bethesda, MD.
 

*CT DEP. 1998. Hazardous limiting values for hazardous air pollutants, Connecticut Department of
 

Environmental Protection, Bureau of Air Management. 22a-174-29.
 

*Daubert TE, Danner RP. 1985. Data compilation tables of properties of pure compounds. Design Institute
 

for Physical Property Data. American Institute of Chemical Engineers, New York, NY.
 

*Davidson BM. 1925. Studies of intoxication: V. The action of ethyl chloride. J Pharmacol Exp Ther
 

26137-42.
 

*Dawkins CJM. 1964. Safety of vinyl ether. Br Med J 2:538.
 

*DHHS. 1994. Seventh annual report on carcinogens: Summary 1994. U.S. Department of Health and 

Human Services, National Institute of Environmental Health Sciences, Research Triangle Park, NC. 
CHLOROETHANE 132 

8. REFERENCES 

*Dobkin AB, Byles PH. 197 1. The pharmacodynamics of divinyl ether, ethylchloride, fluroxene, nitrous 

oxide and trichloroethylene. In: Soma LR ed. Textbook of veterinary anesthesia. Baltimore, MD: Williams 

& Wilkins, 94-104. 

*Doring HJ. 1975. Reversible and irreversible forms of contractile failure caused by disturbances by 

general anesthetics in myocardia.! ATP utilization. Recent Adv Stud Cardiac Struct Metab 5:395-403. 

*Driscoll JN, Duffy M, Pappas S, et al. 1987. Analysis of purgeable organics in water by capillary 

GC/PIDEICD. J Chromatogr Sci 25:369-375. 

*Ebert R, Fedtke N, Certa H, et al. 1994. Genotoxicity studies with chloroethane.Mutat Res 322:33-44 

*Ehrmann, EH. 1977. Pulp testers and pulp testing with particular reference to the use of dry ice. Aust 

Dent J 22:272-279. 

*EPA. 1975. Preliminary assessment of suspected carcinogens in drinking water. Interim report to 

Congress, June, 1975. U.S. Environmental Protection Agency, Office of Toxic Substances, Washington, 

DC., 9. 

EPA. 1979. Chloroethane. In: Water-related environmental fate of 129 priority pollutants. Volume II: 

Halogenated aliphatic hydrocarbons, halogenated ethers, monocyclic aromatics, phthalate esters, 

polycyclic aromatic hydrocarbons, nitrosamines, and miscellaneous compounds. U.S. Environmental 

Protection Agency, Office of Water Planning and Standards, Washington, DC. EPA-440/4-79-029B. 

*EPA. 1981. Treatability manual. Vol. 1. Treatability Data Revised Sept. 198 1. U.S. Environmental 

Protection Agency, Office of Research and Development, Washington, DC. 600/2-82-OOla. 1.12.5-l to 

1.12.5-4. 

*EPA. 1982a. Test methods: Methods for organic chemical analysis of municipal and industrial 

wastewater. Purgeable halocarbon method 601 and EPA No. 60014-82-057. U.S. Environmental 

Protection Agency, Environmental Monitoring and Support Laboratory, Cincinnati, OH. 601-2 to 601 - 10; 

624-l to 624- 12. 

*EPA. 1982b. Test methods for evaluating solid waste. Physical/chemical methods (SW-846). 2nd ed. 

U.S. Environmental Protection Agency, Office of Solid Waste and Emergency Response, Washington, 

DC. l-l 4. 

*EPA. 1985. Regulations of fuel and fuel additives, gasoline lead content. U.S. Environmental Protection 

Agency. Federal Register 50:9386-9399. 

*EPA. 1986a. Superfund record of decisions (EPA Region 3): Tybouts Corner Landfill, New Castle 

County, Delaware, March 1986. Report. US. Environmental Protection Agency, Washington, DC. 

EPA/ROD/R03-86-019. 

*EPA 1986b. Methods for the determination of organic compounds in finished drinking water and raw 

source water. Method Nos 502.1, 524.1 and 524.2. U.S. Environmental Protection Agency, Physical and 

Chemical Methods Branch, Environ Monitoring and Support Lab, Cincinnati, OH. 

*EPA. 1986c. Test methods for evaluating solid waste. Vol. 1B. Laboratory manual: Physical/chemical 

methods. 3rd ed., SW-846. Method No. 8010. U.S. Environmental Protection Agency, Office of Solid 

Waste and Emergency Response, Washington, DC. 8010-1 to 8010-13. 
CHLOROETHANE 133 

8. REFERENCES 

*EPA. 1987. Superfund record of decision (EPA Region 3): Blosenski Landfill, West Cain Township, 

Chester County, Pennsylvania, September 1986. Report. U.S. Environmental Protection Agency, 

Washington, DC. EPA/RODIR03-86/029. l-34. 

*EPA. 1988a. Analysis of Clean Water Act effluent guidelines pollutants. Summary of the chemicals 

regulated by industrial point source category. 40 CFR Parts 400-475. Draft. Prepared by the Industrial 

Technology Division (WH 552), Office of Water Regulations and Standards, Office of Water, U.S. 

Environmental Protection Agency, Washington, DC. 

EPA. 1988b. Summary of emissions associated with sources of ethyl chloride. U.S. Environmental 

Protection Agency, Chemical and Petroleum Branch, Emissions Standards Div., Office of Air Quality 

Planning and Standards. Research Triangle Park, NC. EPA 450/3-88-005. 

*EPA. 1990. Interim methods for development of inhalation reference doses. U.S. Environmental 

Protection Agency. EPA-600/8-90/066A. 

*EPA. 1998a. Designation of hazardous substances. U.S. Environmental Protection Agency. Code of 

Federal Regulations 40 CFR 116.4. 

*EPA. 1998b. Designation, reportable quantities, and notification. U.S. Environmental Protection Agency. 

Code of Federal Regulations 40 CFR 302.4. 

*EPA. 1998c. Toxic chemical release reportin g: Community right-to-know. U.S. Environmental 

Protection Agency. Code of Federal Regulations 40 CFR 372. 

*EPA. 1998d. Methods for organic chemical analysis of municipal and industrial wastewater, method 601. 

U.S. Environmental Protection Agency. Code of Federal Regulations 40 CFR 136 Appendix A. 

*EPA. 1998e. Methods for organic chemical analysis of municipal and industrial wastewater, method 624 

U.S. Environmental Protection Agency. Code of Federal Regulations 40 CFR 136 Appendix A. 

*EPA. 1998f. Drinking water regulations and health advisories. U.S. Environmental Protection Agency, 

Office of Water, Washington, DC. 

*Eškinja M, Lamprecht G, Scherer G, et al. 1997. Assay of S-ethyl-N-acetyl-1-cysteine in urine by 

high-performance liquid chromatography using post-column reaction detection. J Chromatogr B 

704: 159- 165. 

*FEDRIP. 1998. Federal Research in Progress. National Technical Information Service, Springfield, VA. 

May 13, 1998. 

*Fedtke N, Certa H, Ebert R, et al. 1994a. Species differences in the biotransformation of ethyl chloride: 

I.Cytochrome P450-dependent metabolism. Arch Toxicol 68: 158-l 66. 

*Fedtke N, Certa H, Ebert R, et al. 1994b. Species differences in the biotransformation of ethyl chloride: 

II. GSH-dependent metabolism. Arch Toxicol 68:217-223. 

*Ferrario JB, Lawler GC, Deleon IR, et al. 1985. Volatile organic pollutants in biota and sediments of 

Lake Pontchartrain. Bull Environ Contam Toxicol 34:246-255. 
CHLOROETHANE 134 

8. REFERENCES 

*Fidler AT, Baker EL, Letz RE. 1987. Estimation of long term exposure to mixed solvents from 

questionnaire data: A tool for epidemiological investigations. Br J Ind Med 44: 133- 14 1. 

*Finer B. 1966. Divinyl ether and ethyl chloride for outpatients. Acta Anaesthesiol Scand 25:410-412. 

*Fiserova-Bergerova V, Pierce JT, Droz PO. 1990. Dermal absorption potential of industrial chemicals: 

Criteria for skin notation. Am J Ind Med 17:6 17-635. 

*Fisher EM, Koshland CP. 1990. Numerical simulation of the thermal destruction of some chlorinated C1 

and C2 hydrocarbons. J Air Waste Manage Assoc 40: 1384-l 390. 

*Foman SJ. 1966. Body composition of the infant. Part I: The male reference infant. In: Falkner F, ed. 

Human development. Philadelphia, PA: WB Saunders, 239-246. 

*Fornan SJ, Haschke F, Ziegler EE, Nelson SE. 1982. Body composition of reference children from birth 

to age 10 years. Am J Clin Nutr 35:1169-l 175. 

*Gargas ML, Burgess RJ, Voisard DE, et al. 1989. Partition coefficients of low-molecular weight volatile 

chemicals in various liquids and tissues. Toxicol Appl Pharmacol 98:87-99. 

*Gargas ML, Clewell HJ III, Andersen ME. II 990. Gas uptake inhalation techniques and the rates of 

metabolism of chloromethanes, chloroethanes, and chloroethylenes in the rat. Inhal Toxicol 2:295-319. 

*Gohlke R, Schmidt P. 1972. [Subacute action of low concentrations of chlorinated ethanes on rats with 

and without additional ethanol-treatment. II. Histological, histochemical and morphometrical studies.] Int 

Arch Arbeitsmed 30:298-3 12. (German) 

*Goodman ES, Gilman A. 1993. The pharmacological basis of therapeutics. 8th ed. New York, NY: 

McGraw-Hill, Inc., Health Professions Division, 28 1. 

*Gossett JM. 1987. Measurement of Henry’s Law constants for C, and Cz chlorinated hydrocarbons. 

Environ Sci Technol21:202-208. 

*Gould JP, Ramsey RE, Giabbai M, et al. 1983. Formation of volatile haloorganic compounds in the 

chlorination of municipal landfill leachates. Water Chlorin Environ Impact Health Eff 4:525-539. 

*Graedel TE, Hawkins DT, Claxton LD. 1986. Atmospheric chemical compounds sources, occurrence and 

bioassay. New York: Academic Press, 461. 

*Grimsrud EP, Rasmussen RA. 1975. Survey and analysis of halocarbons in the atmosphere by gas 

chromatography-mass spectrometry. Atmos Environ 9:1014- 1017. 

*Guzelian PS, Henry CJ, Olin SS. 1992. Similarities and differences between children and adults: 

Implications for risk assessment. Washington, DC: International Life Sciences Institute Press. 

*Haddad LM, Winchester JF. 1990. Clinical management of poisoning and drug overdose, 2nd ed. 

Philadelphia, PA: W.B. Saunders Company, 1174-l 177. 
CHLOROETHANE 135 

8. REFERENCES 

*Haid B, White JM, Morris LE. 1954. Observations of cardiac rhythm during ethyl chloride anesthesia in 

the dog. Curr Res Anesth Analg 33:3 1 S-325. 

*Haider K. 1980. Degradation of chlorinated aliphatic and aromatic compounds by aerobic and anaerobic 

soil microorganisms. In: Comm Eur Communities (REP) Eur 1980 Eur 6388, Environmental Research 

Programme, 200-204. 

*Hansch C, Leo AJ. 1985. Medchem Project Issue No. 26. Claremont, CA: Pomona College. 

*Hauser TR, Bromberg SM. 1982. EPA monitoring program at Love Canal 1980. Environ Monit Assess 

2:249-271. 

*HazDat. 1996. Hazardous substances database. Agency for Toxic Substance and Disease Registry 

(ATSDR), Atlanta, GA. 

*HazDat. 1998. Hazardous substances database. Agency for Toxic Substance and Disease Registry 

(ATSDR), Atlanta, GA. 

*Hersh R. 199 1. Abuse of ethyl chloride [letter]. Am J Psychiatry 148:270-27 1. 

*Hes JP, Cohn DF, Streifler M. 1979. Ethyl chloride sniffing and cerebellar dysfunction (case report). Isr 

Ann Psychiatr Relat Discip 17: 122- 125. 

*Hiatt MH. 1983. Determination of volatile organic compounds in fish samples by vacuum distillation and 

fused silica capillary gas chromatography/mass spectrometry. Anal Chem 55:506-5 16. 

*Hollinger C, Schraa G, Stupperich E, et al. 1992. Evidence for the involvement of corrinoids and factor 

F430 in the reductive dechlorination of 1,2-dichloroethane by Methanosarcina barkeri. J Bacterial 

174:4427- 4434. 

*Horvath AL. 1982. Halogenated hydrocarbons solubility-miscibility with water. New York: Marcel 

Dekker, Inc., 494-495. 

*Howard CJ, Evenson KM. 1976. Rate constants for the reactions of OH with ethane and some halogen 

substituted ethanes at 296K. J Chem Phys 64:4303-4306. 

*HSDB. 1997. Hazardous Substances Data Bank. National Library of Medicine, National Toxicology 

Information Program, Bethesda, MD. May 11, 1998. 

*Hubrich C, Stuhl F. 1980. The ultraviolet absorption of some halogenated methanes and ethanes of 

atmospheric interest. J Photochem 12:93-107. 

*IARC. 1991. IARC monographs volume 52. Lyons, France: World Health Organization, International 

Agency for Research on Cancer. 3 15-335. 

*ID DHW. 1998. Pollution control rules for control of air pollution in Idaho. Idaho Department of Health 

and Welfare, Division of Environmental Quality. Title 01, Chapter 01.585. 
CHLOROETHANE 136 

8. REFERENCES 

*IRIS. 1997. Integrated Risk Information System. U.S. Environmental Protection Agency, Office of 

Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH. 

May 11, 1998. 

*Jaffe HH, Orchin M. 1962. Theory and application of ultraviolet spectroscopy, New York: John Wiley 

and Sons, Inc., 173-l 74. 

*Jeffers PM, Wolfe NL. 1996. Homogeneous hydrolysis rate constants-Part II: Additions, corrections, and 

halogen effects. Environ Toxicol Chem 15: 1066- 1070. 

*Johanson CE. 1980. Permeability and vascularity of the developing brain: cerebellum vs cerebral cortex. 

Brain Res 190:3- 16. 

*Kenig EE. 1956. [Changes in the peripheral nervous system through the effects of ethyl chloride.] 

[Abstract]. Biological Abstracts 35: 188 Il. (German) 

*Kobayashi H, Rittmann BE. 1982. Microbial removal of hazardous organic compounds. Environ Sd 

Technol 16: 170a- 183a. 

*Komori M, Nishio K, Kitada M, et al. 1990. Fetus-specific expression of a form of cytochrome P-450 in 

human liver. Biochemistry 29:4430-4433. 

*Konietzko H. 1984. Chlorinated ethanes: Sources, distribution, environmental impact and health effects. 

Hazard Assessment of Chemicals 3:401-448. 

*Kriechbaumer N, Hemmer W, Focke M, et al. 1998. Sensitization to ethyl chloride in a handball player. 

Contact Dermatitis 38:227-228. 

*Krishnan K, Andersen ME. 1994. Physiologically-based pharmacokinetic modeling in toxicology. In: 

Hayes W, ed. Principles and methods of toxicology. 3rd edition, New York, NY: Raven Press, Ltd. 

*Krishnan K, Andersen ME, Clewell HJ, III, et al. 1994. Physiologically-based pharmacokinetic modeling 

of chemical mixtures. In: Yang RSA, ed. Toxicology of chemical mixtures, New York, NY: Academic 

Press. 

*Kuschinsky G. 1970. [Death caused by general anesthesia with ethyl chloride.] Dtsch Med Wochenschr 

95:2499. (German) 

*Lamartiniere CA. 198 I. The hypothalamic-hypophyseal-gonadal regulation of hepatic glutathione 

Stransferases in the rat. Biochem J 198:21 l-217. 

*Lamartiniere CA, Lucier GW. 1983. Endocrine regulation of xenobiotic conjugation enzymes. Basic Life 

Sci 24:295-3 12. 

*Landry TD, Ayres JA, Johnson KA, et al. 1982. Ethyl chloride: A two-week inhalation toxicity study and 

effects on liver non-prc?in sulfhydryl concentrations. Fundam Appl Toxicol 2:230-234. 

*Landry TD, Johnson KA, Momany-Pfruender JJ, et al. 1987. Ethyl chloride: 11 -day continuous exposure 

inhalation toxicity study in B6C3Fl mice. The Dow Chemical Company, Midland, MI. NTIS no.OTS05 

17040. Doc # 86-870002250. 
CHLOROETHANE 137 

8. REFERENCES 

*Landry TD, Johnson KA, Phillips JE, et al. 1989. Ethyl chloride (EtCl): 1 l-day continuous exposure 

inhalation toxicity study in B6C3Fl mice. Fundam Appl Toxicol 135 16-522. 

*Langmoen IA, Larsen M, Berg-Johnsen J. 1995. Volatile anaesthetics: Cellular mechanisms of action. 

Eur J Anaesthesiol 125 l-59. 

*Laughton PM, Robertson RE. 1959. Solvolysis in hydrogen and deuterium oxide. Can J Chem 

37:1491-1497. 

*Lawson JIM. 1965. Ethyl chloride. Brit J Anaesth 37:667-670. 

*Lazarew NW. 1929. [Concerning the strength of the narcotic effects of the vapors of the chlorine 

derivatives of the methanes, ethanes and ethylenes.] Arch Exp Path01 Pharmakol 141: 19-24. (German) 

*Leeder JS, Kearns, GL. 1997. Pharmacogenetics in pediatrics: Implications for practice. Ped Clin North 

America 44:55-77. 

*Lehmann KB, Flury F. 1943. Toxicology and hygiene of industrial solvents. Baltimore, MD: William and 

Wilkins Co. 154- 157. 

*Leung H. 1993. Physiologically-based pharmacokinetic modeling. In: Ballantyne B, Marrs T, Turner 

P,eds. General and applied toxicology. Vol. I. New York, NY: Stockton Press, 153-I 64. 

*Lide DR, Frederikse HPR, eds. 1993. CRC handbook of chemistry and physics. 74th ed. Boca Raton, 

FL:CRC Press. 

*Liepins R, Mixon F, Hudak C, et al. 1977. Industrial process profiles for environmental use: Chapter 6. 

The industrial organic chemical industry. U.S. EPA, Research Triangle Park, NC. EPA 600/2-77-023f. 

NTIS PB28 1478. 6-303 to 6-308. 

*Lopez-Avila V, Heath N, Hu A. 1987. Determination of purgeable halocarbons and aromatics by 

photoionization and Hall electrolytic conductivity detectors connected in series. J Chromatogr Sci 

25:356-363. 

*Lyman WJ. 1982. Adsorption coefficient for soils and sediments. In: Lyman WJ, Reehl WF, Rosenblatt 

DH, eds. Handbook of chemical property estimation methods. New York: McGraw-Hill Book Co., 4-l to 

5-29. 

*Mabey W, Mill T. 1978. Critical review of hydrolysis of organic compounds in water under 

environmental conditions. J Phys Chem Ref Data 7:383-415. 

*Mabey WR, Smith JH, Pod011 RT, et al. 198 1. Aquatic fate process data for organic priority pollutants. 

U.S. Environmental Protection Agency, Office of Water Regulations and Standards, Washington, DC. 

EPA-440/4-81-014. 14 l-142. 

*Marbach JJ. 1996. Temporomandibular pain and dysfunction syndrome: History, physical examination, 

and treatment. Rheum Dis Clin North Am 22:477-98. 
CHLOROETHANE 138 

8. REFERENCES 

*McLean S, Robinson J, Starmer GA, et al. 1967. The influence of anaesthetic agents on the formation of 

methaemoglobin induced by aniline in cats. J Pharm Pharmac 19:803-809. 

*Michael LC, Erickson MD, Parks SP, et al. 1980. Volatile environmental pollutants in biological matrices 

with a headspace purge technique. Anal Chem 52: 1836- 1841. 

*Millnan AH, Story DL, Riccio ES, et al. 1988. Rat liver foci and in vitro assays to detect initiating and 

promoting effects of chlorinated ethanes and ethylenes. Ann NY Acad Sci 53452 l-530. 

*Mitre Corp. 1987. National Priority List Technical Data Base (& Base III Version). April, 1987. McLean, 

VA: Mitre Corp., Table 4. 

*Morgan A, Black A, Belcher DR. 1970. The excretion in breath of some aliphatic halogenated 

hydrocarbons following administration by inhalation. Ann Occup Hyg 13:219-233. 

*Morris LE, Noltensmeyer MH, White JM. 1953. Epinephrine induced cardiac irregularities in the dog 

during anesthesia with trichloroethylene, cyclopropane, ethyl chloride and chloroform. Anesthesiology 

14:153-158. 

*Morris TE, Tasto WD. 1979. Ethyl chloride. In: Grayson M, Eckroth D, eds. Kirk-Othmer encyclopedia 

of chemical technology. 3rd ed. Vol. 5. New York, NY: John Wiley and Sons, 714-722. 

*Morsehi PL, France-Morselli R, Bossi L. 1980. Clinical pharmacokinetics in newborns and infants. Clin 

Pharmacokin 5:485-527. 

*Mosesman NH, Sidisky LM, Corman SD. 1987. Factors influencing capillary analysis of volatile 

pollutants. J Chromatogr Sci 25:35 l-355. 

*Myers VB 1983. Remedial activity at the Miami Drum Site, Florida. In: National Conference 

Management of Uncontrolled Hazardous Waste Sites, October 3 1 -November 2, 1983. Silver Spring, MD: 

Hazardous Materials Control Research Institute, 354-357. 

*NAS/NRC. 1989. Biologic markers in reproductive toxicology. National Academy of Sciences/National 

Research Council. Washington, DC: National Academy Press, 15-35. 

*NATICH. 1994. National Air Toxics Information Clearinghouse: Data base report on acceptable ambient 

air concentration guidelines/standards concentrations, units, and averaging times report. US Environmental 

Protection Agency, Office of Air Quality Planning and Standards, Washington, DC. 

*Naylor LM, Loehr RC. 1982. Priority pollutants in municipal sewage sludge. Biocycle 23: 18-22. 

*Nielsen AJ. 1980. Precautions about ethyl chloride [letter]. Phys Ther 60:474-475. 

*NH SDES. 1998. Table containing the list naming all regulated toxic air pollutants. New Hampshire State 

Department of Environmental Services, Air Resources Division. Chapter Env-A 1400, Part Env-A 

1450.01. 

*NIOSH. 199 1. National Occupational Exposure Survey. U.S. Department of Health and Human 

Services,National Institute for Occupational Safety and Health, Cincinnati, OH. 
CHLOROETHANE 139 

8. REFERENCES 

NIOSH. 1992. Recommendations for occupational safety and health. U.S. Department of Health and 

Human Services, Public Health Service, Centers for Disease Control, National Institute for Occupational 

Safety and Health, Cincinnati, OH. NIOSH publication no. 92- 100. 

*NIOSH. 1994. NIOSH manual of analytical methods. 4th ed., NIOSH Publication No. 94-l 13, Method 

No. 2519. U.S. Department of Health and Human Services, Public Health Service, Centers for Disease 

Control, National Institute for Occupational Safety and Health, Cincinnati, OH. 

NIOSH. 1997. NIOSH pocket guide to chemical hazards. U.S. Department of Health and Human Services, 

Public Health Service, Centers for Disease Control, National Institute for Occupational Safety and Health, 

Cincinnati, OH. NIOSH publication no. 94-l 16. 134-l 35. 

*Noble DA. 1979. Another hazard of pierced ears [letter]. Br Med J 1: 125. 

*Nordin C, Rosenqvist M, Hollstedt C. 1988. Sniffing of ethyl chloride - An uncommon form of abuse 

with serious mental and neurological symptoms. Int J Addict 23:623-627. 

*NRC. 1993. Pesticides in the diets of infants and children. National Research Council, Washington DC: 

National Academy Press. 

*NTDB. 1996. National Trade Data Bank: The export connection. U.S. Department of Commerce, 

Economics and Statistics Administration, Washington, DC. (CD-ROM). 

*NTP. 1989. Toxicology and carcinogenesis studies of chloroethane (ethyl chloride) (CAS No. 75-00-3) in 

F344/N rats and B6C3Fl mice (inhalation studies). National Toxicology Program. Research Triangle Park, 

NC. NTP Technical Report Series No. 346. NTIS No. PB90-225053. 

*OHM/TADS. 1998. Oil and Hazardous Materials Technical Assistance Data System. U.S. EPA-NIH 

(National Institute of Health). May 12, 1998. 

*Oliver KD, Adams JR, Daughtrey EH Jr, et al. 1996. Technique for monitoring toxic VOCs in air: 

Sorbent preconcentration, closed-cycle cooler cryofocusing, and GC/MS analysis. Environ Sci Technol 

30: 1939-l 945. 

*OSHA. 1998. U.S. Department of Labor, Occupational Safety and Health Administration. Code of 

Federal Regulations 29 CFR 19 10.1000. 

*OTA. 1990. Neurotoxicity: Identifying and controlling poisons of the nervous system. Office of 

Technology Assessment, Washington, DC. OTA-BA-438. 

*Otson R. 1987. Purgeable organics in Great Lakes raw and treated water. Int J Environ Anal Chem 

31:41-53. 

*Otson R, Chan C. 1987. Sample handling and analysis for 5 1 volatile organics by an adapted purge and 

trap GC-MS technique. Int J Environ Anal Chem 30:275-287. 

*Ott RL. 1969. Local anesthesia in the dog. Fed Proc 28:1450-1455. 
CHLOROETHANE 140 

8. REFERENCES

 *Oura E, Raiha NC, Suomalaimen H. 1966. Influence of some alcohols and narcotics on the adenosine 

phosphates in the liver of the mouse. Ann Med Exp Biol Fenn 45:57-62. 

*Owen GM, Brozek J. 1966. Influence of age, sex, and nutrition on body composition during childhood 

and adolescence. In: Falkner, ed. Human development. Philadelphia, PA: Saunders, 222-238. 

*Pankow JF, Rosen ME. 1988. Determination of volatile compounds in water by purging directly to a 

capillary column with whole column cryotrapping. Environ Sci Technol22:398-405. 

*Parker JC, Casey GE, Bahlman LJ, et al. 1979. Chloroethanes: Review of toxicity. NIOSH Current 

Intelligence Bulletin #27. Am Ind Hyg Assoc J 40:46-60. 

*Pellizzari ED, Erickson MD, Zweidinger RA. 1979. Analytical protocols for making a preliminary 

assessment of halogenated organic compounds in man and environmental media. EPA Report No, 

560/13-79-010. NTIS PB 80109168. 115-137. 

*Pellizzari ED, Hartwell TD, Harris BSH, et al. 1982. Purgeable organic compounds in mother’s milk. 

Bull Environ Contam Toxicol 28:322-328. 

*Pellizzari ED, Perrith K, Hartwell TD, Michael LC, et al. 1987. The Total Exposure Assessment 

Methodology (TEAM) Study. Vol. II. Part I. EPA Report No. 600/6-87/002b, EPA, Office of Research 

and Development, Washington, DC. 145-153. 

*Perry DL, Chuang CC, Jungclaus GA, et al. 1979. Identification of organic compounds in industrial 

effluent discharges. USEPA Office of Research and Development. Athens, GA: EPA-600/4-79-016. NTIS 

PB-294794. 40-41; 43. 

*Rasche ME, Hicks RE, Ilyman MR, et al. 1990. Oxidation of monohalogenated ethanes and n-chlorinated 

alkanes by whole cells of Nitrosomonas europaea. J Bacterial 172:5368-5373. 

*RTECS. 1998. Registry of Toxic Effects of Chemical Substances. National Technical Information 

Service (NTIS), US. Department of Commerce, Springfield, VA. May 11, 1998. 

*Sahel GV, Clark TP. 1984. Volatile organic compounds as indicators of municipal solid waste leachate 

contamination. Waste Management and Research 2: 119- 130. 

*Sayers RR, Yant WP, Thomas BG, et al. 1929. Physiological response attending exposure to vapors of 

methyl bromide, methyl chloride, ethyl bromide and ethyl chloride. U.S. Public Health Bull No. 185: I-56. 

*SC DHEC. 1998. Air pollution control standards, Toxic air pollutants. South Carolina Department of 

Health and Environmental Control, Bureau of Air Quality. 62.5, Standard No. 8. 

*Schmidt P, Binnewies S, Gohlike R, et al. 1972. [Subacute action of low concentrations of 

chlorinatedethanes on rats with and without additional ethanol treatment. I. Subacute and chronic toxicity 

studies with 1 ,I ,2,2-tetrachloroethane.] Int Arch Arbeitsmed 38:283-298. (German) 

*Scortichini BH, Johnson KA, Momany-Pfruenderd JJ, et al. 1986. Ethyl chloride: Inhalation teratology 

study in CF-1 mice. Dow Chemical Company, Mammalian and Environmental Toxicology Research 

Laboratory, Health and Environmental Sciences, Midland, MI. NTIS no. OTS0001135. 
CHLQROETHANE 141 

8. REFERENCES 

*Selby IR, Bowles BJM. 1995. Analgesia for venous cannulation: A comparison of EMLA (5 minute 

application), lignocaine, ethyl chloride, and nothing. J R Sot Med 88:264-267. 

*Setchell BP, Waites GMH. 1975. The blood testis barrier. In: Creep RO, Astwood EB, Greiger SR, 

eds.Handbook of physiology: Endocrinology V. Washington, DC: American Physiological Society. 

*Shepson PB, Kleindiemst TE, Mcelhoe HB. 1987. A cryogenic trap/porous polymer sampling technique 

for the quantitative determination of ambient volatile organic compound concentrations. Atmos Environ 2 

1:579-587. 

*Singh HB, Salas LJ, Smith A, et al. 1981. Atmospheric measurements of selected hazardous organic 

chemicals. NTIS No. PB81-200628. 

*Singh HB Salas LJ, Stiles RE. 1983. Selected man-made halogenated chemicals in the air and oceanic 

envirbonment. J Geophys Res [Sect] C 88:3675-3683. 

*Staples CA, Werner A, Hoogheem T. 1985. Assessment of priority pollutant concentrations in the United 

States using STORET database. Environ Toxicol Chem 4: 13 l-l 42. 

*Stutz DR, Ulin S. 1992. Hazardous materials injuries. Beltsville, MD: Bradford Communications 

Corporation, 286-287. 

*Swann RL, Laskowski DA, McCall PJ, et al. 1983. A rapid method for the estimation of the 

environmental parameters octanol/water partition coefficient, soil sorption constant, water to air ratio and 

water solubility. Res Rev 85: 17-28. 

*Tabak HH, Quave SA. Mashni CI, et al. 1981. Biodegradability studies with organic priority pollutant 

compounds. J Water Pollut Control Fed 53:1503-l 5 18. 

Takano T, Miyazaki Y. 1982. Effect of chlorinated ethanes and ethylenes on electron transport in rat liver 

mitochondria. J Toxicol Sci 7: 143- 149. 

*Tennant RW, Ashby J. 1991. Classification according to chemical structure, mutagenicity to Salmonella 

and level of carcinogenicity of a further 39 chemicals tested for carcinogenicity by the U.S. National 

Toxicology Program. Mutat Res 257:209-227. 

*Thomas R. 1982. Volatilization from water. In: Lyman WJ, Reehl WF, Rosenblatt DH, eds. Handbook of 

chemical property estimation methods. New York: McGraw Hill Book Co., Chapter 15. 

*Torkelson TR, Rowe VK. 198 1. Ethyl chloride. In: Clayton GD and Clayton FE, eds. Patty’s industrial 

hygiene and toxicology Vol2B. 3rd ed. New York: John Wiley and Sons, Inc., 3480-3483. 

*TRI96. 1998. Toxics Release Inventory for 1996. U.S. Environmental Protection Agency, Office of 

Toxic Substances, Washington, DC. 

*Troshina MM. 1966. [Some materials for substantiation of the maximum admissible concentration of 

ethyl chloride in the air of work places.] Gig Tr Prof Zabol 10:37-42. (Russian) 
CHLOROETHANE 142 

8. REFERENCES 

*Tu AS, Murray TA, Hatch KM, et al. 1985. In vitro transformation of BALB/c-3T3 cells by chlorinated 

ethanes and ethylenes. Cancer Lett 28:85-92. 

USITC. 1984. United States International Trade Commission. Synthetic organic chemicals United States 

production and sales, 11983. USITC Publication 1588. Washington, DC: USITC, 259. 

USITC. 1985. United States International Trade Commission. Synthetic organic chemicals United 

Statesproduction and sales, 11984. USITC Publication 1745. Washington, DC: USITC, 258. 

USITC. 1986. United States International Trade Commission. Synthetic organic chemicals United States 

production and sales, 11985. USITC Publication 1892. Washington, DC: USITC, 268. 

USITC. 1987. United States International Trade Commission. Synthetic organic chemicals United States 

production and sales, 11986. USITC Publication 2009. Washington, DC: USITC, 2 12-213. 

*Van Dyke RA, Wineman CG. 197 1. Enzymatic dechlorination: Dechlorination of chloroethanes and 

propanes in vitro. Biochem Pharmacol20:463-470. 

*Van Ketel WG. 1976. Allergic contact dermatitis from propellants in deodorant sprays in combination 

with allergy to ethyl chloride. Contact Dermatitis 2: 115-l 19. 

*Van Liere EJ, Mazzocco TR, Northup DW. 1966. The effect of cyclopropane, trichloroethylene and ethyl 

chloride on the uterus of the dog. Am J Obstet Gynecol994:861-867. 

*Vieira I, Sonnier M, Cresteil T. 1996. Developmental expression of CYP2El in the human liver: 

Hypermethylation control of gene expression during the neonatal period. Eur J Biochem 238:476-483. 

*Vogel TM, McCarty PL. metcanogenic conditions.1987. Abiotic and biotic transformations of 1,l ,l ­

trichloroethane under Environ Sci Technol2 1: 1208-l 2 13. 

*Vogt WG Walsh JJ. 1985. Volatile organic compounds in gases from landfill simulators. Proc Air 

Pollttion Control Association Annu Meet 78:2- 17. 

*WA DE. 1998. Toxic air pollutants and acceptable source impact levels. Washington Department of 

Ecology. WAC 173-460-l 60. 

*Walker JS, Soult TA. 1993. Ethyl chloride intoxication [letter]. Am J Emerg Med 11:3 13-3 15. 

*Wailer CL, Evans MV, McKinney JD. 1996. Modeling the cytochrome P450-mediated metabolism of 

chlorinated volatile organic compounds. Drug Metab Dispos 24:203-210. 

*Washington JW. 1996. Gas partitioning of dissolved volatile organic compounds in the vadose zone: 

Principles, temperature effects and literature review. Ground Water 34:709-7 18. 

*Watanabe Y. 1983. [Studies on the biologic effects of hydrocarbons (III)-chlorinated hydrocarbons.] 

Kanagawa-ken Taiki Osen Chosa Kenkyu Hokoku 25: 146- 152. (Japanese) 

*West JR, Smith HW, Chasis H. 1948. Glomerular filtration rate, effective renal blood flow, and maximal 

tubular excretory capacity in infancy. J Ped 32a: 10- 18. 
CHLOROETHANE 143 

8. REFERENCES 

*Widdowson EM, Dickerson JWT. 1964. Chemical composition of the body. In: Comar CL, Bronner F, 

eds. Mineral metabolism: An advanced treatise, volume II, The elements part A. New York, NY: 

Academic Press. 

*Worrall S, De Jersey J, Wilce PA, et al. 1994. Studies on the usefulness of acetaldehyde-modified 

proteins and associated antibodies as markers of alcohol abuse. Alcohol Alcohol Suppl2:503-507. 

*Yacoub I, Robinson CA, Simmons GT. 1993. Death attributed to ethyl chloride. J Anal Toxicol 17:384­

385. 

*Young DR, Gossett RW, Baird RB, et al. 1983. Wastewater inputs and marine bioaccumulation of 

priority pollutant organics off southern California. In: Jolley RL, ed. Proceedings of the Fourth Conference 

on Water Chlorination-Environmental Impacts and Health Effects, October 18-23, 198 1. Ann Arbor, MI: 

Ann Arbor Science, 87 1-884. 

*Young P, Parker A. 1984. Vapors, odors and toxic gases from landfills. In: Jackson LP, Rohlik AR, 

Conway RA, eds. Hazardous and Industrial Waste Management and Testing: Third Symposium, March 7­

10, 1983. Philadelphia, PA: ASTM Technical Publication, 24-41. ASTM Publication Code Number 04­

851000-16. 

*Ziegler EE, Edwards BB, Jensen RL, et al. 1978. Absorption and retention of lead by infants. Pediatr Res 

12:29-34. 

CHLOROETHANE 145 

9. GLOSSARY
 

Acute Exposure-Exposure to a chemical for a duration of 14 days or less, as specified in the Toxicological
 

Profiles.
 

Adsorption Coefficient (Koc)-The ratio of the amount of a chemical adsorbed per unit weight of organic
 

carbon in the soil or sediment to the concentration of the chemical in solution at equilibrium.
 

Adsorption Ratio (Kd)-The amount of a chemical adsorbed by a sediment or soil (i.e., the solid phase)
 

divided by the amount of chemical in the solution phase, which is in equilibrium with the solid phase, at a
 

fixed solid/solution ratio. It is generally expressed in micrograms of chemical sorbed per gram of soil or
 

sediment.
 

Bioconcentration Factor (BCF)-The quotient of the concentration of a chemical in aquatic organisms at a
 

specific time or during a discrete time period of exposure divided by the concentration in the surrounding
 

water at the same time or during the same period.
 

Cancer Effect Level (CEL)-The lowest dose of chemical in a study, or group of studies, that produces
 

significant increases in the incidence of cancer (or tumors) between the exposed population and its
 

appropriate control.
 

Carcinogen-A chemical capable of inducing cancer.
 

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.
 

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.
 

Embryotoxicity and Fetotoxicity-Any toxic effect on the conceptus as a result of prenatal exposure to a
 

chemical; the d istinguishing feature between the two terms is the stage of development during which the
 

insult occurred. The terms, as used here, include malformations and variations, altered growth, and in
 

utero death.
 

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.
 

Immediately Dangerous to Life or Health (IDLH)-The maximum environmental concentration of a
 

contaminant from which one could escape within 30 min without any escape-impairing symptoms or
 

irreversible health effects.
 

Intermediate Exposure-Exposure to a chemical for a duration of 15-364 days, as specified in the
 

Toxicological Profiles.
 
CHLOROETHANE 146 

9. GLOSSARY 

Immunologic Toxicity-The occurrence of adverse effects on the immune system that may result from
 

exposure to environmental agents such as chemicals.
 

In Vitro-Isolated from the living organism and artificially maintained, as in a test tube.
 

In Vivo-Occurring within the living organism.
 

Lethal Concentratioq(LO) (LCLO)-The lowest concentraGon of a chemical in air which has been reported to
 

have caused death in humans or animals.
 

Lethal Concentration (50) (LC50) - A calculated concentration of a chemical in air to which exposure for a 

specific length of time is expected to cause death in 50% of a defined experimental animal population. 

Lethal Dose(50)_(LD50)-The lowest dose of a chemical introduced by a route other than inhalation that 

isexpected to have caused death in humans or animals. 

Lethal Dose(50) (LD50)-The dose of a chemical which has been calculated to cause death in 50% of a 

defined experimental animal population. 

Lethal Time(50) (LT50)-A calculated period of time within which a specific concentration of a chemical is 

expected to cause death in 50% of a defined experimental animal population. 

Lowest-Observed-Adverse-Effect Level (LOAEL)-The Aowest dose of chemical in a study, or group of 

studies, that produces statistically or biologically significant increases in frequency or severity of adverse 

effects between the exposed population and its appropriate control. 

Malformations-Permanent structural changes that may adversely affect survival, development, or function. 

Minimal Risk Level-An estimate of daily human exposure to a dose of a chemical that is likely to be 

without an appreciable risk of adverse noncancerous effects over a specified duration of exposure. 

Mutagen-A substance that causes mutations. A mutation is a change in the genetic material in a body cell. 

Mutations can lead to birth defects, miscarriages, or cancer. 

Neurotoxicity-The occurrence of adverse effects on the nervous system following exposure to chemical. 

No-Observed-Adverse-Effect Level (NOAEL)-The dose of chemical at which there were no statistically or 

biologically significant increases in frequency or severity of adverse effects seen between the exposed 

population and its appropriate control. Effects may be produced at this dose, but they are not considered to 

be adverse. 

Octanol-Water Partition Coefficient (Kow) -The equilibrium ratio of the concentrations of a chemical in noctanol and water, in dilute solution. 

Permissible Exposure Limit (PEL)-An allowable exposure level in workplace air averaged over an 8-hour 

shift. 
CHLOROETHANE 147 

9. GLOSSARY 

q1*-The upper-bound estimate of the low-dose slope of the dose-response curve as determined by the 

multistage procedure. The ql* can be used to calculate an estimate of carcinogenic potency, the 

incremental excess cancer risk per unit of exposure (usually μL for water, mg/kg/day for food, and μg/m3 

for air). 

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 NOAEL (from animal and human 

studies) by a consistent application of uncertainty factors that reflect various types of data used to estimate 

RfDs and an additional modifying factor, which is based on a professional judgment of the entire database 

on the chemical. The RfDs are not applicable to nonthreshold effects such as cancer. 

Reportable Quantity (RQ)-The quantity of a hazardous substance that is considered reportable under 

CERCLA. Reportable quantities are (1) 1 pound or greater or (2) for selected substances, an amount 

established by regulation either under CERCLA or under Sect. 311 of the Clean Water Act. Quantities are 

measured over a 24-hour period. 

Reproductive Toxicity-The occurrence of adverse effects on the reproductive system that may result from 

exposure to a chemical. The toxicity may be directed to the reproductive organs and/or the related 

endocrine system. The manifestation of such toxicity may be noted as alterations in sexual behavior, 

fertility, pregnancy outcomes, or modifications in other functions that are dependent on the integrity of this 

system. 

Short-Term Exposure Limit (STEL)-The maximum concentration to which workers can be exposed for up 

to 15 mm continually. No more than four excursions are allowed per day, and there must be at least 60 min 

between exposure periods. The daily TLV-TWA may not be exceeded. 

Target Organ Toxicity-This term covers a broad range of adverse effects on target organs or physiological 

systems (e.g., renal, cardiovascular) extending from those arising through a single limited exposure to 

those assumed over a lifetime of exposure to a chemical. 

Teratogen-A chemical that causes structural defects that affect the development of an organism. 

Threshold Limit Value (TLV)-A concentration of a substance to which most workers can be exposed 

without adverse effect. The TLV may be expressed as a TWA, as a STEL, or as a CL. 

Time-Weighted Average (TWA)-An allowable exposure concentration averaged over a normal g-hour 

workday or 40-hour workweek. 

Toxic Dose (TD50)-A calculated dose of a chemical, introduced by a route other than inhalation, which is 

expected to cause a specific toxic effect in 50% of a defined experimental animal population. 

Uncertainty Factor (UF)-A factor used in operationally deriving the RfD from experimental data. UFs are 

intended to account for (1) the variation in sensitivity among the members of the human population, (2) the 

uncertainty in extrapolating animal data to the case of human, (3) the uncertainty in extrapolating from 

data obtained in a study that is of less than lifetime exposure, and (4) the uncertainty in using LOAEL data 

rather than NOAEL data. Usually each of these factors is set equal to 10. 

CHLOROETHANE A-1 

APPENDIX A 

ATSDR MINIMAL RISK LEVELS AND WORKSHEETS 

The Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) [42 U.S.C. 

9601 et seq.], as amended by the Superfund Amendments and Reauthorization Act (SARA) [Pub. L. 

994991, requires that the Agency for Toxic Substances and Disease Registry (ATSDR) develop jointly 

with the U.S. Environmental Protection Agency (EPA), in order of priority, a list of hazardous substances 

most commonly found at facilities on the CERCLA National Priorities List (NPL); prepare toxicological 

profiles for each substance included on the priority list of hazardous substances; and assure the initiation 

of a research program to fill identified data needs associated with the substances. 

The toxicological profiles include an examination, summary, and interpretation of available toxicological 

information and epidemiologic evaluations of a hazardous substance. During the development of 

toxicological profiles, Minimal Risk Levels (MRLs) are derived when reliable and sufficient data exist to 

identify the target organ(s) of effect or the most sensitive health effect(s) for a specific duration for a given 

route of exposure. An MRL is an estimate of the daily human exposure to a hazardous substance that is 

likely to be without appreciable risk of adverse noncancer health effects over a specified duration of 

exposure. MRLs are based on noncancer health effects only and are not based on a consideration of 

cancer effects. These substance-specific estimates, which are intended to serve as screening levels, are 

used by ATSDR health assessors to identify contaminants and potential health effects that may be of 

concern at hazardous waste sites. It is important to note that MRLs are not intended to define clean-up or 

action levels. 

MRLs are derived for hazardous substances using the no-observed-adverse-effect 1eveVuncertainty factor 

approach. They are below levels that might cause adverse health effects in the people most sensitive to 

such chemical-induced effects. MRLs are derived for acute (1-14 days), intermediate (15-364 days), and 

chronic (365 days and longer) durations and for the oral and inhalation routes of exposure. Currently, 

MRLs for the dermal route of exposure are not derived because ATSDR has not yet identified a method 

suitable for this route of exposure. MRLs are generally based on the most sensitive chemical-induced end 

point considered to be of relevance to humans. Serious health effects (such as irreparable damage to the 

liver or kidneys, or birth defects) are not used as a basis for establishing MRLs. Exposure to a level above 

the MRL does not mean that adverse health effects will occur. 
CHLOROETHANE A - 2 

APPENDIX A 

MRLs are intended only to serve as a screening tool to help public health professionals decide where to 

look more closely. They may also be viewed as a mechanism to identify those hazardous waste sites that 

are not expected to cause adverse health effects. Most MRLs contain a degree of uncertainty because of 

the lack of precise toxicological information on the people who might be most sensitive (e.g., infants, 

elderly, nutritionally or immunologically compromised) to the effects of hazardous substances. ATSDR 

uses a conservative (i.e., protective) approach to address this uncertainty consistent with the public health 

principle of prevention. Although human data are preferred, MRLs often must be based on animal studies 

because relevant human studies are lacking. In the absence of evidence to the contrary, ATSDR assumes 

that humans are more sensitive to the effects of hazardous substance than animals and that certain persons 

may be particularly sensitive. Thus, the resulting MRL may be as much as a hundredfold below levels that 

have been shown to be nontoxic in laboratory animals. 

Proposed MRLs undergo a rigorous review process: Health Effects/MRL Workgroup reviews within the 

Division of Toxicology, expert panel peer reviews, and agencywide MRL Workgroup reviews, with 

participation from other federal agencies and comments from the public. They are subject to change as 

new information becomes available concomitant with updating the toxicological profiles. Thus, MRLs in 

the most recent toxicological profiles supersede previously published levels. For additional information 

regarding MRLs, please contact the Division of Toxicology, Agency for Toxic Substances and Disease 

Registry, 1600 Clifton Road, Mailstop E-29, Atlanta, Georgia 30333. 
CHLOROETHANE A - 3 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical Name: Chloroethane 

CAS Number: 75-00-3 

Date: November 1998 

Profile Status: Post-Public 

Route: [x] Inhalation [ ] Oral 

Duration: [x] Acute [] Intermediate [ ] Chronic 

Graph Key: 30 

Species: Mice (CF-1) 

Minimal Risk Level: 15 [ ] mg/day [x] ppm 

Reference: Scortichini et al. 1986 

Experimental design: Groups of 23-26 pregnant mice were exposed to 99.9% pure chloroethane at 0,49 1, 

1504, or 4,946 ppm 6 hours/day on gestation days 6-15. Body weights were recorded on gestation days 

6,9, 12, 15, and 18, and food and water intakes were measured. The animals were sacrificed on gestation 

day 18 and the following data were recorded: maternal liver weight; number and position of fetuses in 

utero; number of live and dead fetuses; number and position of resorption sites; weight and sex of each 

fetus; gross externalalterations. Half of each litter was examined for visceral alterations, half for skeletal 

alterations. 

Effects noted in study and corresponding doses: No maternal toxicity (body weight, food and water 

intake,liver weight) was observed. There were no effects on reproductive parameters, fetal body weight, or 

malformations. A small increase in the incidence of foramina of the skull bones (small centers of 

unossified bone) was observed at the high dose that was statistically significant (p = 0.05) (percent of 

litters affected 5%, 4%, 4%, 23%; percent of fetuses affected l%, l%, l%, 4% at 0,491, 1,504, and 4,946 

ppm, respectively). An increase in supernumerary ribs was also found, although the effect was not 

indicated as statistically significant. The incidence of fetuses with supernumerary ribs was 2/257 (1%) 

controls, and in increasing concentrations l/299 (0.3%), 6/311 (2%), and 2/242 (2%). The incidence in 

litters was 2/22 (9%) controls, l/25 (4%), 5/26 (19%), and 4/22 (18%). The authors indicate that the effect 

was “suggestive of, at most, very slight fetotoxicity” at the high dose. 

Dose and end point used for MRL derivation: 

[x] NOAEL [ ] LOAEL 

1,504 ppm 

Uncertainty Factors used in MRL derivation: 

[ ] 10 for use of a LOAEL 

[x] 10 for extrapolation from animals to humans 

[x] 10 for human variability 

Was a conversion used from ppm in food or water to a mg/body weight dose? No. 

If so, explain: 
CHLOROETHANE A-4 

APPENDIX A 

If an inhalation study in animals. list the conversion factors used in determining human equivalent dose: 

Because fetotoxic effects may result from peak concentrations rather than total duration of exposure, the 

NOAEL was not adjusted for intermittent exposure. 

Because chloroethane is lipid soluble it is reasonable to assume that periodicity was attained. Therefore, a 

human equivalent concentration (HEC) could be calculated by multiplying the NOAEL by the ratio of the 

human/mouse blood gas partition coefficients. The value for humans is 2.69 (Gargas et al. 1989). The 

value for mice is not known. Since the human/mouse ratio is unknown, a default value of 1 is used. 

Other additional studies or uertinent information which lend support to this MRL: 

There are no additional developmental or reproductive studies of chloroethane. A study by Bucher et al. 

(1995) reported a small increase in the average duration of the estrous cycle in female mice exposed to 

chloroethane at 15,000 ppm 6 hours/day for 21 days. No consistent effects on estradiol or progesterone 

effects were noted. No other exposure concentrations were used in this study. 

Other studies have not identified clear dose-related effects of chloroethane in animals at concentrations up 

to 19,000 ppm (Landry et al. 1982, 1987, 1989; NTP 1989). Because of an explosion hazard (chloroethane 

is explosive at 40,000 ppm), intermediate- and chronic duration toxicity studies have not examined higher 

concentrations. 
CHLOROETHANE B-l 

APPENDIX B 

USER’S GUIDE 

Chapter 1 

Public Health Statement 

This chapter of the profile is a health effects summary written in non-technical language. Its intended 

audience is the general public especially people living in the vicinity of a hazardous waste site or chemical 

release. If the Public Health Statement were removed from the rest of the document, it would still 

communicate to the lay public essential information about the chemical. 

The major headings in the Public Health Statement are useful to find specific topics of concern. The topics 

are written in a question and answer format. The answer to each question includes a sentence that will 

direct the reader to chapters in the profile that will provide more information on the given topic. 

Chapter 2 

Tables and Figures for Levels of Significant Exposure (LSE) 

Tables (2-1,2-2, and 2-3) and figures (2-l and 2-2) are used to summarize health effects and illustrate 

graphically levels of exposure associated with those effects. These levels cover health effects observed at 

increasing dose concentrations and durations, differences in response by species, minimal risk levels 

(MRLs) to humans for noncancer end points, and EPA’s estimated range associated with an upper- bound 

individual lifetime cancer risk of 1 in 10,000 to 1 in 10,000,000. Use the LSE tables and figures for a 

quick review of the health effects and to locate data for a specific exposure scenario. The LSE tables and 

figures should always be used in conjunction with the text. All entries in these tables and figures represent 

studies that provide reliable, quantitative estimates of No-Observed-Adverse- Effect Levels (NOAELs), 

Lowest-Observed-Adverse-Effect Levels (LOAELs), or Cancer Effect Levels (CELs). 

The legends presented below demonstrate the application of these tables and figures. Representative 

examples of LSE Table 2-l and Figure 2-l are shown. The numbers in the left column of the legends 

correspond to the numbers in the example table and figure. 

LEGEND 

See LSE Table 2-l 

(1) Route of Exposure One of the first considerations when reviewing the toxicity of a substance 

using these tables and figures should be the relevant and appropriate route of exposure. When 

sufficient data exists, three LSE tables and two LSE figures are presented in the document. The 

three LSE tables present data on the three principal routes of exposure, i.e., inhalation, oral, and 

dermal (LSE Table 2-1,2-2, and 2-3, respectively). LSE figures are limited to the inhalation (LSE 

Figure 2-l) and oral (LSE Figure 2-2) routes. Not all substances will have data on each route of 

exposure and will not therefore have all five of the tables and figures. 
CHLOROETHANE	 B - 2 

APPENDIX B 

(2)	 Exposure Period Three exposure periods - acute (less than 1.5 days), intermediate (15-364 days), 

and chronic (365 days or more) are presented within each relevant route of exposure. In this 

example, an inhalation study of intermediate exposure duration is reported. For quick reference to 

health effects occurring from a known length of exposure, locate the applicable exposure period 

within the LSE table and figure. 

(3)	 Health Effect The major categories of health effects included in LSE tables and figures are death, 

systemic, immunological, neurological, developmental, reproductive, and cancer. NOAELs and 

LOAELs can be reported in the tables and figures for all effects but cancer. Systemic effects are 

further defined in the “System” column of the LSE table (see key number 18). 

(4)	 Key to Figure Each key number in the LSE table links study information to one or more data 

points using the same key number in the corresponding LSE figure. In this example, the study 

represented by key number 18 has been used to derive a NOAEL and a Less Serious LOAEL 

(also see the 2 “18r” data points in Figure 2-l). 

(5)	 Species The test species, whether animal or human, are identified in this column. 

“Relevance to Public Health,” covers the relevance of animal data to human toxicity and Section 

2.3, “Toxicokinetics,” contains any available information on comparative toxicokinetics. 

Although NOAELs and LOAELs are species specific, the levels are extrapolated to equivalent 

human doses to derive an MRL. 

(6)	 Exposure Frequency/Duration The duration of the study and the weekly and daily exposure 

regimen are provided in this column. This permits comparison of NOAELs and LOAELs from 

different studies. In this case (key number 18), rats were exposed to 1,1,2,2-tetrachloroethane via 

inhalation for 6 hours per day, 5 days per week, for 3 weeks. For a more complete review of the 

dosing regimen refer to the appropriate sections of the text or the original reference paper, i.e., 

Nitschke et al. 1981. 

(7)	 System This column further defines the systemic effects. These systems include: respiratory, 

cardiovascular, gastrointestinal, hematological, musculoskeletal, hepatic, renal, and 

dermal/ocular. “Other” refers to any systemic effect (e.g., a decrease in body weight) not covered 

in these systems. In the example of key number 18, 1 systemic effect (respiratory) was 

investigated. 

(8)	 NOAEL A No-Observed-Adverse-Effect Level (NOAEL) is the highest exposure level at which 

no harmful effects were seen in the organ system studied. Key number 18 reports a NOAEL of 3 

ppm for the respiratory system which was used to derive an intermediate exposure, inhalation 

MRL of 0.005 ppm (see footnote “b”). 

(9)	 LOAEL A Lowest-Observed-Adverse-Effect Level (LOAEL) is the lowest dose used in the study 

that caused a harmful health effect. LOAELs have been classified into “Less Serious” and 

“Serious” effects. These distinctions help readers identify the levels of exposure at which adverse 

health effects first appear and the gradation of effects with increasing dose. A brief description of 

the specific endpoint used to quantify the adverse effect accompanies the LOAEL. The respiratory 

effect reported in key number 18 (hyperplasia) is a Less serious LOAEL of 10 ppm. MRLs are not 

derived from Serious LOAELs. 

(10) Reference The complete reference citation is given in chapter 8 of the profile. 
CHLOROETHANE	 B - 3 

APPENDIX B 

(11) CEL A Cancer Effect Level (CEL) is the lowest exposure level associated with the onset of 

carcinogenesis in experimental or epidemiologic studies. CELs are always considered serious 

effects, The LSE tables and figures do not contain NOAELs for cancer, but the text may report 

doses not causing measurable cancer increases. 

(12)	 Footnotes Explanations of abbreviations or reference notes for data in the LSE tables are found in 

the footnotes. Footnote “b” indicates the NOAEL of 3 ppm in key number 18 was used to derive 

an MRL of 0.005 ppm. 

LEGEND 

See Figure 2-1 

LSE figures graphically illustrate the data presented in the corresponding LSE tables. Figures help the 

reader quickly compare health effects according to exposure concentrations for particular exposure 

periods. 

(13)	 Exposure Period The same exposure periods appear as in the LSE table. In this example, health 

effects observed within the intermediate and chronic exposure periods are illustrated. 

(14) Health Effect These are the categories of health effects for which reliable quantitative data e 

exists. The same health effects appear in the LSE table. 

(15)	 Levels of Exposure concentrations or doses for each health effect in the LSE tables are 

graphically displayed in the LSE figures. Exposure concentration or dose is measured on the log 

scale “y” axis. Inhalation exposure is reported in mg/m3

 or ppm and oral exposure is reported in 

mg/kg/day. 

(16)	 NOAEL In this example, 18r NOAEL is the critical endpoint for which an intermediate inhalation 

exposure MRL is based. As you can see from the LSE figure key, the open-circle symbol 

indicates to a NOAEL for the test species-rat. The key number 18 corresponds to the entry in the 

LSE table. The dashed descending arrow indicates the extrapolation from the exposure level of 3 

ppm (see entry 18 in the Table) to the MRL of 0.005 ppm (see footnote “b” in the LSE table). 

(17)	 CEL Key number 38r is 1 of 3 studies for which Cancer Effect Levels were derived. The diamond 

symbol refers to a Cancer Effect Level for the test species-mouse. The number 38 corresponds to 

the entry in the LSE table. 

(18)	 Estimated Upper-Bound Human Cancer Risk Levels This is the range associated with the upperbound for lifetime cancer risk of 1 in 10,000 to 1 in 10,000,000. These risk levels are derived 

from the EPA’s Human Health Assessment Group’s upper-bound estimates of the slope of the 

cancer dose response curve at low dose levels (ql *). 

(19)	 Key to LSE Figure The Key explains the abbreviations and symbols used in the figure. 


CHLOROETHANE B - 6 

APPENDIX B 

Chapter 2 (Section 2.5) 

Relevance to Public Health 

The Relevance to Public Health section provides a health effects summary based on evaluations of existing 

toxicologic, epidemiologic, and toxicokinetic information. This summary is designed to present 

interpretive, weight-of-evidence discussions for human health end points by addressing the following 

questions. 

1. What effects are known to occur in humans? 

2. What effects observed in animals are likely to be of concern to humans? 

3. What exposure conditions are likely to be of concern to humans, especially around 

hazardous waste sites? 

The section covers end points in the same order they appear within the Discussion of Health Effects by 

Route of Exposure section, by route (inhalation, oral, dermal) and within route by effect. Human data are 

presented first, then animal data. Both are organized by duration (acute, intermediate, chronic). In vitro 

data and data from parenteral routes (intramuscular, intravenous, subcutaneous, etc.) are also considered in 

this section. If data are located in the scientific literature, a table of genotoxicity information is included. 

The carcinogenic potential of the profiled substance is qualitatively evaluated, when appropriate, using 

existing toxicokinetic, genotoxic, and carcinogenic data. ATSDR does not currently assess cancer potency 

or perform cancer risk assessments. Minimal risk levels (MRLs) for noncancer end points (if derived) and 

the end points from which they were derived are indicated and discussed. 

Limitations to existing scientific literature that prevent a satisfactory evaluation of the relevance to public 

health are identified in the Data Needs section. 

Interpretation of Minimal Risk Levels 

Where sufficient toxicologic information is available, we have derived minimal risk levels (MRLs) for 

inhalation and oral routes of entry at each duration of exposure (acute, intermediate, and chronic). These 

MRLs are not meant to support regulatory action; but to acquaint health professionals with exposure levels 

at which adverse health effects are not expected to occur in humans. They should help physicians and 

public health officials determine the safety of a community living near a chemical emission, given the 

concentration of a contaminant in air or the estimated daily dose in water. MRLs are based largely on 

toxicological studies in animals and on reports of human occupational exposure. 

MRL users should be familiar with the toxicologic information on which the number is based. Chapter 2.5, 

“Relevance to Public Health,” contains basic information known about the substance. Other sections such 

as 2.8, “Interactions with Other Substances,” and 2.9, “Populations that are Unusually Susceptible” 

provide important supplemental information. 

MRL users should also understand the MRL derivation methodology. MRLs are derived using a modified 

version of the risk assessment methodology the Environmental Protection Agency (EPA) provides (Barnes 

and Dourson 1988) to determine reference doses for lifetime exposure (RfDs). 
CHLOROETHANE B - 7 

APPENDIX B 

To derive an MRL, ATSDR generally selects the most sensitive endpoint which, in its best judgement, 

represents the most sensitive human health effect for a given exposure route and duration. ATSDR cannot make 

this judgement or derive an MRL unless information (quantitative or qualitative) is available for all potential 

systemic, neurological, and developmental effects. If this information and reliable quantitative data on the 

chosen endpoint are available, ATSDR derives an MRL using the most sensitive species (when information 

from multiple species is available) with the highest NOAEL that does not exceed any adverse effect levels. 

When a NOAEL is not available, a lowest-observed-adverse-effect level (LOAEL) can be used to derive an 

MRL, and an uncertainty factor (UF) of 10 must be employed. Additional uncertainty factors of 10 must be 

used both for human variability to protect sensitive subpopulations (people who are most susceptible to the 

health effects caused by the substance) and for interspecies variability (extrapolation from animals to humans). 

In deriving an MRL, these individual uncertainty factors are multiplied together. The product is then divided 

into the inhalation concentration or oral dosage selected from the study. Uncertainty factors used in developing 

a substance-specific MRL are provided in the footnotes of the LSE Tables.