National Institute on Drug Abuse

RESEARCH

MONOGRAPH SERIES

Inhalant Abuse: A

Volatile Research

Agenda

U.S. Department of Health and Human Services • Public Health Service • National Institutes of Health

129
Inhalant Abuse: A Volatile

Research Agenda

Editors:

Charles Wm. Sharp, Ph.D.

Fred Beauvais, Ph.D.

Richard Spence, Ph.D.

NIDA Research Monograph 129

1992

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES

Public Health Service

National Institutes of Health

National Institute on Drug Abuse

5600 Fishers Lane

Rockville, MD 20857
ACKNOWLEDGMENT

This monograph is based on the papers from a technical review on “Inhalant

Abuse” held in 1989. The review meeting was sponsored by the National

Institute on Drug Abuse and the Texas Commission on Alcohol and Drug

Abuse.

COPYRIGHT STATUS

The National Institute on Drug Abuse has obtained permission from the

copyright holders to reproduce certain previously published material as noted

in the text. Further reproduction of this copyrighted material is permitted

only as part of a reprinting of the entire publication or chapter. For any other

use, the copyright holder’s permission is required. All other material in this

volume except quoted passages from copyrighted sources is in the public

domain and may be used or reproduced without permission from the Institute

or the authors. Citation of the source is appreciated.

Opinions expressed in this volume are those of the authors and do not

necessarily reflect the opinions or official policy of the National Institute on

Drug Abuse or any other part of the Department of Health and Human

Services.

The U.S. Government does not endorse or favor any specific commercial

product or company. Trade, proprietary, or company names appearing in this

publication are used only because they are considered essential in the context

of the studies reported herein.

National Institute of Drug Abuse

NIH Publication No. 93-3475

Printed 1992

NIDA Research Monographs are indexed in the Index Medicus. They are

selectively included in the coverage of American Statistics Index, BioSciences

Information Service, Chemical Abstracts, Current Contents, Psychological

Abstracts, and Psychopharmacology Abstracts.

ii
In Memoriam

Sidney Cohen, M.D.

1910-1987

Throughout his distinguished career as a physician, researcher, mentor, author,

and Federal administrator, to name some of the major roles he played, Dr.

Sidney Cohen represented the highest level of integrity and commitment to

truth. Perhaps it was that essential commitment that enabled Sid to avoid

being seduced by the “psychedelic revolution” embraced so uncritically by

some of his colleagues in the early 1960s. But he also never succumbed to the

hysteria that maintained that all the problems of youths could be uncritically

attributed to their drug use. His sense of proportion, good humor, and wide

ranging knowledge of both science and history gave him a rare and wise

perspective during a troubled era.

Sid Cohen’s impressive skills as a communicator enabled him to make

important contributions to both drug abuse research and to the public’s

understanding of the drug problem. Because he liked young people and was

liked and respected by them, he was particularly effective in communicating

with youths. And, since he did not shrink from asking himself the hard

questions, he did not hesitate to ask them of the young as well. He was among

the first to debate Timothy Leary, the self-styled “psychedelic drug guru,” on

college campuses, pointing out, “A pill does not construct character, educate

the emotions, or improve intelligence. It is not a spiritual labor-saving device,

salvation, instant wisdom, or a short cut to maturity.” This was in the early

1960s when many who should have known better thought LSD and the other

hallucinogens were all those things.

Sid was a gifted writer. Through hundreds of scientific articles as well as

numerous books for lay audiences he conveyed the subtlety and complexity of

psychoactive drugs and the hazards of their abuse. Sid’s popular books

included such classics as The Beyond Within and The Drug Dilemma, both of

which went through several editions.

iii
As a psychopharmacologist, Sid was very aware of the importance of not only

the drug itself, but of its dosage and circumstances of use. Never a polemicist,

Sid felt his greatest contribution to the drug dialogue was to make the public

aware of the seductive hazards of drugs by acquainting them with the

implications of scientific research. Some felt they knew all the answers. Sid

was much more conscious of the unanswered questions. As a drug historian,

Sid was very aware of how often a new analgesic, stimulant, or “recreational

drug,” intitially thought to be nonaddictive, was later found to produce

dependency.

Sid Cohen’s energies were legendary. To the very end of his life he was

astonishingly productive as well as virtually a “commuter” between the west

and east coasts in his many roles as administrator, consultant, or member of

innumerable advisory boards on topics ranging from drug abuse to suicide

prevention and schizophrenia. Drugs, and later psychopharmacology were,

however, his basic preoccupation, beginning with his early training as a

pharmacist (at Columbia University) in the early 1930s. He received his

medical training in Germany (at Bonn University) during those

turbulent—and for him potentially perilous—years in which the Nazis rose to

power. In 1976, his alma mater, Columbia University, awarded him an

honorary Doctor of Science degree in acknowledgement of his many

contributions to psychopharmacology.

Toward the end of his life some of us sometimes wished Sid would find time

to “enjoy life” more. But we forgot that for Sid to continue to work in his

chosen field was more fun than anything else he could imagine. He had a

small plaque on his desk that said, “It is not necessary to succeed in order to

try.” Surely he succeeded far better than he knew. We continue to miss his

unfailing good humor, his wisdom, his perceptiveness, and his dedication to

truth.

Robert C. Petersen, Ph.D.

iv
Sidney Cohen and I entered the field of drug abuse at about the same

time—more than 30 years ago. We also began by studying the same class of

drugs, hallucinogens. One other point we shared was that we had both been

trained in internal medicine, not psychiatry.

Although not specifically trained as a psychiatrist, Sidney could have been cast

in such a role in any movie. His physical appearance was imposing. A leonine

mane of graying hair swept back in pompadour style from his forehead,

beneath which were a pair of piercing eyes. He conveyed an Old World charm

legitimately obtained from his origin. His slightly raspy voice and the words

he spoke showed empathy and compassion. I am sure that he must have been

a good clinician.

His research efforts in the field of substance abuse spanned many years and

were well recognized by his peers. However, his greatest service might have

been as an administrator. When the drug abuse problem showed signs of

becoming a national menace, Sidney was lured from his comfortable southern

California existence to come to Washington to administer the program that

later evolved into NIDA. As a result of his efforts, funding for drug abuse

research grew rapidly and mechanisms were established to distribute

controlled substances to qualified investigators. He was one of the first

persons to recognize the importance of inhalant abuse. When things were

finally going well, he rejoined his family in California.

Sidney was one of the most lucid lecturers I have ever heard. No fancy

language, no jargon, but just good straightforward English. He was always

careful with his facts but not afraid to slip in some sly humor. He was an

excellent spokesman for the field of drug abuse and was active in many

community activities as well as at the national level. He was a devoted

husband who took good care of his wife, Elsa, after she had the misfortune to

develop Parkinson’s disease. He had many colleagues who also became his

good friends.

No one is irreplaceable, but Sidney’s death left a void that many of us still feel.

It is entirely appropriate that this volume be dedicated to one of the pioneers

in drug abuse research—a true scholar and gentleman.

Leo E. Hollister, M.D.

v
I respectfully conclude this tribute by noting that Sidney Cohen, a valuable

colleague in the early period of the development of NIDA’s Inhalant

Program, was primary in supporting both my and the Institute’s efforts. Not

only because of his general knowledge and experience in the field of drug

abuse, but also because of his interest in those abusing inhalants, he perceived

the need for the investigation of the toxicology and drug dependence

associated with solvent intoxication. Thus, he guided both me and NIDA in

the early stages of this program and endorsed the accumulation of knowledge

in this emerging field. Our efforts culminated in the first publication,

Inhalant Abuse: Euphoria to Dysfunction, in 1977. Periodically thereafter,

conversations often focused on recent advances in the field to which he

contributed recent knowledge and relevant guidance, both of which were

invaluable. He would be proud of the advances in the field which have been

identified within this monograph, but always cognizant of, and quick to

identify, the many challenges that lie ahead. I regret that he is not with us

now to discuss the pertinent issues and thoughtfully approach and

scientifically design studies to provide the necessary data that would allow us

to reduce those tragedies associated with this state of drug dependency.

Charles W. Sharp, Ph.D.

vi
Preface

In the fall of 1989, the University of Texas, Health Sciences Center, and the

Texas Commission on Alcohol and Drug Abuse convened a meeting to review

the present state of our knowledge concerning inhalant abuse and to

stimulate increased inquiry into various aspects of this complex problem.

During this meeting it became obvious that, unlike other areas of drug abuse

research, no cohesive group of investigators has directly addressed research or

treatment in the area of inhalant abuse. The lack of cohesion of inquiry into

solvent abuse may result, in part, from both the unusual patterns shown by the

abusers and the nature of the substances themselves. Many dimensions that

differentiate inhalant abusers from other drug abusers are extensively

described in this volume. Not only does this group of abusers utilize an

enormous array of substances, the individuals themselves are a complex crosssection of many sociocultural and psychological dimensions. Many exhibit

particularly dysfunctional behavior patterns, making them especially

refractory to treatment. While volatile solvent abusers share a number of

characteristics with other drug abusers, enough differences exist to make

many researchers and treatment personnel reluctant to become involved with

these populations and their behavior. Understandably, many investigators

prefer to focus on less complex behaviors that offer greater promise for

understanding and treatment.

The National Institute on Drug Abuse was pleased to cooperate with the

Texas Commission on Alcohol and Drug Abuse in sponsoring this important

meeting. The participants included established as well as new investigators

from both the public and private sectors.

The format of the conference focused on broad fields of endeavor. Each

section was introduced by a review of the state of our knowledge in a

particular area followed by discussions and relevant short papers. Following

the meeting, the papers were revised for the NIDA Research Monograph

series and updated to present an intelligible review of the field.

vii
It is hoped that this monograph will be a beginning step in the process of

bringing more coherence to what heretofore has been an unfocused area of

inquiry.

James V. Dingell, Ph.D.

Director

Division of Preclinical Research

National Institute on Drug Abuse

viii
Contents

Introduction to Inhalant Abuse 1

Charles W. Sharp

Section I

Volatile Solvent Abuse: Trends and Patterns 13

Fred Beauvais

Epidemiology of Volatile Substance Abuse: The Texas Experience 43

Eric V. Fredlund

Epidemiology of Inhalant Abuse: A Canadian View 51

Reginald G. Smart

Section II

Psychosocial Characteristics and Their Links With Inhalants:

A Research Agenda 59

E. R. Oetting and Jay Webb

Ethnomethodology, Psychosocial Measures, and

Inhalant Abuse Research 99

Joseph E. Trimble

Comments on Psychosocial Characteristics 111

Daniel L. Creson

ix
Contents (Continued)

Section III

Solvent Toxicity: A Neurological Focus 117

Neil Rosenberg and Charles W. Sharp

Clinical/Biophysiologic Aspects of Inhalant Abuse 173

Milton Tenenbein

Death Among Inhalant Abusers 181

James C. Garriott

Sudden Sniffing Death Following Inhalation of Butane

and Propane: Changing Trends 193

Earl Siegel and Suman Wason

Section IV

Treatment of Volatile Solvent Abusers 203

Pamela Jumper-Thurman and Fred Beauvais

A Longitudinal Study of Inhalant Use: Implications

for Treatment and Prevention 215

D. Dwayne Simpson

Treatment and Prevention Research Issues 229

Leo E. Hollister

x
Contents (Continued)

Section V

Animal Research on Solvent Abuse 233

Gordon T. Pryor

Basic Science Solvent Abuse Research Issues 259

Richard A. Meisch

Animal Research as a Guide to Regulation and

Prevention of Solvent Abuse 263

Ronald W. Wood

Section VI

An Industrial/Economic Perspective of Inhalant Abuse 275

Robert P. Giovacchini

Development of Alternative Fluorocarbons 287

Henry J. Trochimowicz

Section VII

Recommendations 301

xi

Introduction to Inhalant Abuse

Charles W. Sharp

The term “inhalant abuse” is used to describe a variety of drug abuse

behaviors that cannot be classified by the associated pharmacology or toxicology, but only by the mode of administration. Yet, some other inhaled substances (e.g., tobacco, marijuana, and even heroin or “crack”) do not fall into

this classification. Leo Hollister has identified abused inhalants as groups of

volatile substances used for altering mental status that are rarely, if ever, administered by routes other than inhalation. On this basis several subcategories can be established: (a) medical anesthetic gases, such as ether, chloroform, halothane, and nitrous oxide; (b) industrial or household solvents, including paint thinners or solvents, degreasers, and solvents in glues; (c) art

and office supply solvents, including correction fluids and solvents in markers;

(d) gases used in household or commercial products, e.g., in butane lighters,

whipping cream dispensers, electronic equipment dusters and cleaners (e.g.,

for PCs), and refrigerant replenishers; (e) household aerosol propellants in

items such as paint, hair, and fabric protector sprays; and (f) aliphatic nitrites.

(There are substantive reasons for considering the nitrites as a special class.

First, they act on vascular smooth muscle rather than as anesthetic agents on

the central nervous system. Second, they are used as sexual enhancers,

primarily by specific populations.)

Volatile substances (or “inhalants”) are ubiquitous and their use as intoxicants

extends well back into history. The practice of inhalation to produce

euphoria can be traced to the ancient Greeks (Carroll 1977). As Hollister has

noted:

1
At the turn of the 18th century, Humphry Davy in England,

experimenting with the newly discovered gas, nitrous oxide,

discovered its mind-altering effects. He shared his fun with

friends at a succession of private parties. Later, charlatans

took the gas on the road, with travelling exhibitions at which

for a fee, the audience might experience the effects of the gas.

Commonly called “laughing gas,” the euphemism accurately describes one of

the recreational uses of the anesthetic nitrous oxide. In the mid-19th century,

after the discovery of the anesthetic action of ether and chloroform, these

gases were also used nonmedically—e.g., chloroform and ether parties. These

substances are still used today by inhalant abusers (Hutchens and Kung 1985;

Kringsholm 1980). That these substances are abused by middle class professionals demonstrates the diversity of the groups that abuse inhalants (Nordin

et al. 1988; Krause and McCarthy 1989; Jacob et al. 1989). Nearly all solvents

produce anesthesia if sufficient amounts are inhaled. Although this is an important property, the ability to produce anesthesia does not seem to correlate

with the extent of abuse of any given substance.

The 20th century brought on the use of gasoline and many other volatile

compounds. Hollister notes that the present period of use of inhalants probably dates from the 1920s but expanded rapidly following World War II.

These solvents can be found in numerous products that are everywhere—in

industry, in the workplace, and in the home. Thus, in our industrial society, it

is not difficult to find some substance to “get high on”—and at a bargain price.

Substances Inhaled

Despite the widespread abuse of these substances for years, it was not until

the 1950s that nationwide attention focused on what was generally referred to

as “glue sniffing” by the press (see Kerner 1988) and the judicial system. The

term is still widely (mis)used to describe an activity involving a myriad of

products that include not only glue but gasoline, paint thinner, spray paint,

cooking spray, deodorant, hair spray, correction fluid, cleaning fluid,

refrigerant gases, cooking gases, tobacco-lighter gases, anesthetics, canned

whipped cream, dust remover aerosols, and fabric protector sprays. It is important to keep in mind that there are many different chemicals in these

products, all of which have diverse physiological effects, toxicities, and

2
chemical properties. Sometimes the substances are listed on the container

with or without the proportion of each.

Because of the diversity and complex composition of different products, there

are often incorrect references to which particular solvents are being abused.

Toluene, for example, is often cited as the substance involved when other substances may also be present and may contribute to the problem, or even be the

primary substance at issue. Also, some reports associating toluene with a particular syndrome may have missed the substance that is the actual cause of

that syndrome. To correctly identify the substance, it is critical that clinical

measures of body fluids be conducted to correlate a clinical syndrome with a

particular substance(s). Clues may be derived from containers, but that is often not helpful as many products do not identify all the substances and may

often only refer to ingredients as “nontoxic hydrocarbons.”

Some of the possible substances found in different products are listed in table

1.

Sociocultural Factors

The practices of “sniffing,” “snorting,” “huffing,” “bagging,” or otherwise inhaling to get high describe various forms of inhalation abuse. If the substance

is glue or some other dissolved solid, the user will empty the product’s contents into a plastic bag, hold the bag to the nose, and inhale (“bagging”).

Another method is to soak a rag with the mixture and then stick the rag in the

mouth and inhale the fumes (“huffing”). A simple but more toxic approach is

to spray the substance directly into the oral cavity. Abusers can be identified

by various telltale clues, including organic chemical odors on the breath or

clothes, stains on the clothes or around the mouth, empty spray paint or solvent containers, and the presence of unusual paraphernalia. These telltale

clues may point to a serious problem of solvent abuse, that may, in turn, lead

to a serious health problem or death.

The bases for inhaling solvents are well described, as Sidney Cohen did a

decade and a half ago (Cohen 1977). These substances are widely available,

readily accessible, cheap, and legally obtained. As with other recreational

substances they may make users temporarily forget their problems and relieve

boredom—providing a quick high, with a rapid dissipation and a minimal

hangover. Subjects who use heavily over short periods often complain of

3
Table 1. Chemicals commonly found in inhalants

Adhesives

Airplane glue toluene, ethyl acetate

Other glues hexane, toluene, methyl chloride, acetone,

methyl ethyl ketone, methyl butyl ketone

Special cements trichloroethylene, tetrachloroethylene

Aerosols

Spray paint

Hair spray

Deodorant; air

freshener

Analgesic spray

Asthma spray

Fabric spray

PC cleaner

Anesthetics

Gaseous

Liquid

Local

Cleaning Agents

Dry cleaning

Spot remover

Degreaser

butane, propane (U.S.), fluorocarbons,

toluene, hydrocarbons, [“Texas shoe

shine,” a spray containing toluene]

butane, propane (U.S.), CFCs

butane, propane (U.S.), CFCs

chlorofluorocarbons (CFCs)

chlorofluorocarbons (CFCs)

butane, trichloroethane

dimethyl ether, hydrofluorocarbons

nitrous oxide

halothane, enflurane

ethyl chloride

tetrachloroethylene, trichloroethane

xylene, petroleum distillates,

chlorohydrocarbons

tetrachloroethylene, trichloroethane,

trichloroethylene

4
Table 1. (Continued). Chemicals commonly found in inhalants

Solvents and Gases

Nail polish

remover

Paint remover

Paint thinner

Correction fluid

and thinner

Fuel gas

Lighter

Fire extinguisher

Food Products

Whipped cream

Whippets

“Room Odorizers”

Locker Room,

Rush, Poppers

acetone, ethyl acetate

toluene, methylene chloride, methanol

acetone, ethyl acetate

petroleum distillates, esters, acetone

trichloroethylene, trichloroethane

butane, isopropane

butane, isopropane

bromochlorodifluoromethane

nitrous oxide

nitrous oxide

isoamyl, isobutyl, isopropyl or butyl

nitrite (now illegal), cyclohexyl

5
headaches. Many solvent abusers, more than other drug users, are poor, come

from broken homes, and do poorly in school (Korman et al. 1981; Oetting et

al. 1988).

Oetting et al. (1988) have usefully categorized those who use inhalants into

three groups: (1) inhalant-dependent adults, (2) polydrug users, and (3) young

inhalant users. The first group will have the most serious health problems

because they have used heavily for a long time; the last group will be those for

whom treatment is most desirable to keep them from progressing to the first

group and for whom there may be hope for successful intervention if caught in

the early phases. Although all inhalant abusers use other drugs or alcohol,

the first group predominately uses inhalants even though other drugs are

available. The second group infrequently uses inhalants primarily in instances

when they can not get their drug of choice; their problems will arise more

from the use of other drugs and not be related to those discussed in this volume. The last group, young inhalant users, generally is in the experimentation period with solvents—having started with tobacco, alcohol, and possibly

even marijuana as well as inhalants. Behavioral intervention is very important to dissuade members of this group from maturing into the first group.

One aspect of the inhalant abuse problem is often brought up but not answered to anyone’s satisfaction. That is, why are certain specific substances

inhaled? Some consider the odor to be important; others believe that the

feeling one gets is most important. It is also difficult to say with certainty

which substances are most preferred. Rankings of ever-used substances place

glue and gasoline at the top (analysis of the National Household Survey data,

1991). Gasoline still topped the list upon analysis of past-month-used, which

is followed by spray paint and other aerosols, nitrous oxide, correction fluid,

and with glue being last. Additionally a Texas school survey (Fredlund et al.

1989) ranked correction fluids at the top with glue, gasoline, and spray paint

being the next most frequent. A survey of delinquent children ranked paint

sprays as the most frequently used substance (Fredlund et al. 1990) with

nitrites also high on the list.

The now less-accessible fluorocarbons seem to be used very little (by general

disclosures from the field and as per the Texas survey), possibly because they

are available primarily only in the pressurized refrigerant replacement cans.

However, there are still numerous deaths attributed to the abuse of fluorocarbons (Litovitz et al. 1990). The addictive nature of fluorocarbons is

6
exemplified by cases of asthma inhalers who inhale beyond the point of medication (Thompson et al. 1983). This is one of the few marketable forms of

fluorocarbons in substances used by the general public other than the pressurized refrigerant refillers used for air conditioning systems. The United

States banned the use of fluorocarbons as the propellant for most commercial

applications at the onset of the 1980s because of the atmospheric pollution issue. There are new propellants being utilized in the anticipation that they will

produce limited damage to the atmosphere (see Trochimowicz, this volume);

however, little is known about their effects when used for recreational purposes. However, some of the new substitute fluorocarbons are singularly present without other ingredients in products used to clean contact points on

electronic equipment. These products are apparently desirable to solvent

abusers; this type of abuse has resulted in several reported deaths.

The more limited abuse of frying pan coaters today may suggest a lower desire

for the butane and isopropane used by some inhalant abusers to replace the

fluorocarbons. However, the abuse of butane lighter and other cooking gases

here and in England (Anderson 1990, Ramsey et al. 1989; Mathew et al. 1989;

Evans and Raistrick 1987a,b; Siegel and Wason 1990) refute that hypothesis.

The availability of the pure gas in pressurized containers (such as lighters)

nullifies the need for separating these gases from other substances in aerosols.

It is indeed unusual that these very dangerous substances are inhaled, and it is

hard to tell whether this is just a passing fancy or whether some really do like

the dizzy effect they cause and will continue to use butane and propane gases.

A recent report of deaths in the Cincinnati region (see Siegel and Wason’s

chapter, this volume) would indicate that the use of butane gas is a serious

problem. The abuse of fuel gases, whether or not it will be a short-lived form

of inhalant abuse, can be lethal (Siegel and Wason, this volume).

Evans and Raistrick (1987a,b) summarized a test group of sniffers’ perceptions of butane gas vs. toluene. Moods, thoughts, hallucinations (except tactile), and colors appeared similar under both compounds; however, time

passed slowly under butane and more rapidly under toluene. This one study

would indicate that butane may be an acceptable substitute for one of the

most widely abused substances—toluene—and will thus be a substance of

concern. In an effort to reduce the undesired exposure to cooking gases, it is

now mandatory to add thiols, a substance with an unpleasant aroma, to some

portable gas containers such as propane tanks. It has also been suggested that

7
thiols be added to all forms of gas containers in a manner similar to that for

the natural gas supply.

The bottom line is that a variety of substances are used, and the extent to

which they are used may be based more on availability than individual preference. Yet, sniffers do seem to go out of their way to get their favorite,

whether it is gold spray paint, whippets, lighter gas, “Texas shoe-shine” or

another local or current favorite. All of these products, while apparently

desirable to inhalant abusers, have resulted in deaths.

It is not the intent of this introduction to summarize the physiological, psychological, or social problems associated with this form of drug abuse; this

information is provided and extensively discussed in the following chapters.

One word of caution, however, to readers. Not all inhalants act alike. Some,

for example, cause peripheral nerve damage (hexane) while others may act

both centrally and peripherally (toluene, nitrous oxide) and others may not

cause any irreversible neurological damage (butane, chlorofluorocarbons).

Some solvents are toxic to the liver (chlorohydrocarbons) or kidneys

(probably toluene). Only benzene has been associated with leukemia or

oncogenic changes. Therefore, one should be very careful in globally stating

that “inhalants” cause all of these medical sequelae. The fact that numerous

exposures are necessary to cause any of these reactions can be reassuring to

parents of youths “caught in the act.” Time, however, will not be on the sniffer’s side when overdose occurs and results in the rapid onset of death.

It is anticipated that this introduction will pave the way for the reader to more

fully appreciate the in-depth discourse of the following chapters that enumerate our knowledge and ignorance of this subject. It is hoped that the reader

will become more knowledgeable and thus be able to conduct further research

and/or appropriate treatment that will help lead to a resolution of, and even

more importantly prevent, the many tragedies surrounding inhalant abuse.

References

Anderson, H.R. Increase in deaths from deliberate inhalation of fuel gases

and pressurised aerosols [letter] Brit Med J 301(6742):41, Jul. 7, 1990.

Carroll, E. Notes on the epidemiology of inhalants. In: Sharp, C.W., and

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Kringsholm, B. Sniffing-associated deaths in Denmark. Forensic Sci Int

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Mathew, B.; Kapp, E.; and Jones, T.R. Commercial butane abuse, a

disturbing case. Br J Addict 84(5):563-564, 1989.

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uncommon form of abuse with serious mental and neurological

symptoms. Int J Addict 23(6):623-627, 1988.

Oetting, E.R.; Edwards, R.W.; and Beauvais, F. Social and psychological factors underlying inhalant abuse. In: Crider, R., and Rouse, B., eds.

Epidemiology of Inhalant Abuse: An Update. Research Monograph 85.

DHHS Pub. No. (ADM)88-1577. Rockville, MD: National Institute on

Drug Abuse, 1988. pp. 172-203.

Ramsey, J.; Anderson, H.R.; Bloor, K.; and Flanagan, R.J. An introduction to

the practice, prevalence and chemical toxicology of volatile substance

abuse. Hum Toxicol 8(4):261-269, 1989.

Siegel, E., and Wason, S. Sudden death caused by inhalation of butane and

propane. N Engl J Med 323:1638, 1990.

Thompson, P.J.; Dhillon, P.; and Cole, P. Addiction to aerosol treatment:

The asthmatic alternative to glue sniffing. Brit Med J 287:1515, 1983.

10
Author

Charles W. Sharp, Ph.D.

National Institute on Drug Abuse

5600 Fishers Lane, Room 10A-31

Rockville, MD 20857

11

Volatile Solvent Abuse: Trends

And Patterns

Fred Beauvais

The study of the abuse of volatile solvents is hampered by a number of factors

not usually found in the study of other drugs of abuse. Consequently, the

quality of the research data is very uneven, and many contradictory findings

appear in the literature. This chapter first discusses the problems encountered in this area of inquiry, then reviews the available data on the patterns,

trends and distribution of volatile solvent abuse, and finally presents a series

of recommendations for future research.

Definition and Terminology

Most drugs of abuse are grouped according to the effects experienced by

users, and to a large extent, this is related to a specific biochemical action

within the central or peripheral nervous system. For example, recent evidence

has identified the euphoric and addictive effects of cocaine as emanating from

disturbances in the neurotransmitter balance in certain midbrain areas, more

specifically in the basic reward centers (Brown 1989). It is likely that

methamphetamine has a very similar biochemical action, and thus, the clinical

picture for its use and the use of cocaine could be similar. It is then useful to

discuss both drugs as stimulants and to look for common factors in their use

and consequences of use. In the same way, it is possible to categorize and discuss other categories of drugs, such as “downers,” psychedelics, and tranquilizers, which have similar neurological activity.

13
The term “inhalants,” however, has come to encompass a group of psychoactive chemicals that are defined by the route of administration rather than by

their experienced effects or central nervous system (CNS) action. Thus, such

diverse substances as toluene, ether, and the nitrites have been included under

the rubric of inhalants because they are all taken in through the nose. This

can lead to a great deal of confusion, since not only may the psychoactive

properties be different, but the profiles of the typical users of the various substances are quite diverse. For example, it would be difficult to reconcile the

motivational or behavioral pattern of a physician who chronically abuses

anesthetics with that of a street huffer who is addicted to spray paint.

There is usually some understanding among those in the drug abuse field that

the term “inhalant users” applies to those who use volatile commercial solvents. This convention, however, is not universal, and it is not unusual in the

literature for anything that is sniffed or huffed to be considered an inhalant.

The resulting discussion of epidemiological and clinical issues can only be

ambiguous. The most common case of overinclusion occurs with amyl and

butyl nitrites. These are very often considered the equivalent of industrial and

household solvents and little distinction is made between the users of each

type of substance. In a very large national data base collected over the past 3

years, we have been able to show significant differences between nitrite users

and those who use common household solvents. (See Oetting and Beauvais

[1990] for a description of the data base.)

The prevalence rates for nitrites and solvents for high school seniors are listed

in table 1. Although it is apparent that some youths use both nitrites and solvents, the majority use only one or the other and are likely to differ on a

number of important dimensions.

The lack of clarity as to what constitutes an inhalant leads to measurement

problems in the assessment of incidence and prevalence rates. These problems arise from poor conceptualization of the questions included on surveys

and from subsequent confusion on the part of the respondents. The inhalant

question on the National High School Senior Drug Abuse Survey (Johnston

et al. 1988), for instance, is broad enough to include the use of both solvents

and nitrites, although nitrites are not specifically referenced in the question.

From 1975 to 1979 this was the only question asking about drugs that are inhaled and was the sole basis for reporting inhalant rates. Subsequent to 1979

14
Table 1. Percentage of high school seniors (N=31,782) using volatile

solvents, nitrites, and both substances.

Ever Used in

used past 30 days

Used in

past year

Volatile solvents 11.2 1.6 4.3

Nitrites 10.2 1.0 3.0

Both substances 4.8 0.3 1.0

a separate question was added asking about nitrites. Based on responses to

this question the inhalant prevalence rates were adjusted upward. The

reasoning on the part of the survey developers was that many students were

not including nitrites when they responded to the inhalant question, so the

inhalant question response rate needed upward adjustment. Obviously, these

researchers consider inhalants to include nitrites. The net result is confusion

when the long-term trends in inhalant use are examined—the unadjusted

rates (including only volatile solvents) show gradual increases over time, but

when adjusted for nitrite use, which their data show as decreasing, the longterm trends in inhalant use appear stable (figure 1). In combining solvents

with nitrites (i.e., adjusting the solvent data), it appears that inhalant use has

not changed over the past 13 years whereas, in fact, solvent use has steadily

increased.

Poorly worded questions also lead to inaccurate results. Many surveys ask,

“Have you ever inhaled anything to get high?” Without further qualification,

many students will include the use of cocaine, powdered stimulants, or even

the sniffing of heroin when responding to this question. The results are quite

clearly confounded.

15
Figure 1. Lifetime prevalance for high school seniors for inhalants, inhalants

adjusted, and nitrites

16
Arriving at a Standard Definition

There have been several attempts to establish a convention regarding the nature of what constitutes inhalants. Beauvais and Oetting (1987) have argued

that inhalant abuse should be restricted to the use of volatile solvents and

should exclude the use of the nitrites and anesthetic gases. This is based on

differences in both the neurochemical actions and the clinical profiles of the

users of these three classes of substances. This convention is also followed in

DSM-III-R, where the diagnoses “inhalant abuse” and “inhalant induced organic mental disorder” are restricted to the use of volatile solvents (American

Psychiatric Association 1987). Abuse of nitrites and gaseous anesthetics is

given a separate diagnosis.

The most consistent attempt to arrive at a common label was in the journal

Human Toxicology. The entire July 1989 issue was devoted to various aspects

of the abuse of volatile solvents. Throughout the issue, the term “volatile solvent abuse” (VSA) was used to denote the behavior. This not only provides a

common terminology but also restricts the issue to solvents and excludes

other psychoactive substances that are inhaled, in particular, the nitrites and

anesthetic gases. This approach seems very reasonable as long as the label is

used carefully and is not applied indiscriminately to all levels of solvent use.

As is discussed later, it is very common for many young people to have a single episode, or a short period, of inhaling substances, and it would be inappropriate to refer to these as abuse. Perhaps another convention, “volatile

solvent use,” would be appropriate for these less severe patterns. As with any

convention, there will be exceptions. Butane, chloroflourocarbon propellents, and certain forms of nitrous oxide have been used quite heavily in certain populations, and technically, they are not solvents. Because of their

manner of use and the groups who use them, it would seem reasonable to

classify people abusing these substances as volatile solvent abusers. There no

doubt will be other exceptions in the future that will have to be considered on

a case-by-case basis for classification.

Variability by Location

The use of volatile solvents is often characterized by short-term episodic patterns that occur in a school, community, or region. Periodically, a “new” solvent will be discovered by a small group of young people, and its use will

quickly spread in a fashion very typical of teenage fads. The pattern of use for

17
this substance will be widespread but not very heavy for any of the individuals

involved. Just as abruptly, use will drop off and rates will return to low levels.

While episodic patterns are noted for other drugs, they do not seem to be as

dramatic as those patterns seen with solvents. The reasons for this are unclear, but they may be related to the unusual age period of solvent use, which

is discussed below.

An example of an episodic pattern is presented in figure 2. These data come

from a western U.S. community where drug use data have been available annually since 1982. For both grades (an aggregated sample of three high

schools and six junior high schools) solvent use increased through 1984, followed by a sharp decrease in 1985 and then an increase for the next 2 years.

The important pattern here is the decrease from 1984 to 1985. For the 12th

graders, the rate dropped by over one half. A number of methodological reasons for this were explored, including the wording and placement of the items

on the survey from year to year. After this examination, however, the pattern

still seems valid. As a further indication of validity, the age of first use of solvents for the various cohorts differed, suggesting that the factors influencing

use had in fact varied from year to year. Large variations from year to year

(i.e., from class to class) might be expected if the data were restricted to one

school. In this instance, however, data from several schools were aggregated,

and the lifetime prevalence rates for the other drugs asked about on the survey did not fluctuate. This suggests that attitudes toward solvents can shift

very quickly and that information regarding acceptability or sanctions is

rapidly communicated among youths.

This episodic pattern has important implications for the generalizability of

survey results, especially in studies that are very local in nature. If a survey is

conducted at the high point of an episode, it may lead to the conclusion that a

massive intervention is needed. While it may not be wise to ignore the problem, it is equally inappropriate to overreact and not let the outbreak take its

normal course. One of the problems with an overreaction is the possibility

that the use of solvents could actually be exacerbated. Brecher (1972, p. 327)

made this point 20 years ago in his description, “How To Start an Epidemic.”

In this analysis he felt that the extensive publicity given to a small outbreak of

solvent use caused it to spread far beyond where it could have normally been

contained. Many young people who were not aware that solvents could produce a euphoric effect learned the behavior through prevention activities.

18
Figure 2. Trends in lifetime prevalence of volatile solvent use among 8th and 12th graders in a

western U.S. school district
Another pattern that commonly occurs with volatile solvent abuse is localized

endemics. Once again, the reasons for this are not known but may be related

to isolation, availability, or simply a behavior that has few sanctions and that

becomes entrenched in certain areas. Once established, the pattern is passed

on from older to younger children. There is even a more insidious, intergenerational pattern consisting of parents teaching their children to use solvents

as a means of making them more docile and tractable. (To date these reports

are anecdotal and need more exploration.) If a survey happens to be conducted in one of these areas and high rates of solvent use are found, care must

be taken to avoid erroneous generalization. As an example, a study over a

decade ago in a Los Angeles barrio found that Hispanic children had rates of

solvent use 14 times that found for Anglo youths (Padilla et al. 1979). Several

subsequent studies in inner-city barrios reported similar findings, and it became well accepted that solvent abuse was a particularly serious problem

among Hispanics. More recent studies, however, have sampled Hispanic

youths in other geographic contexts and have not found these high rates

(Oetting and Beauvais 1990). It appears that the rates for Hispanics may be a

function of socioeconomic conditions, and as those conditions vary, so will the

levels of solvent use. Hispanic youths in poor barrio environments may use

solvents heavily, but Hispanic youths in less stressful environments do not.

Age Patterns of Solvent Use

Typically, lifetime prevalence rates for drug use increase with age throughout

adolescence, peaking in late adolescence and then leveling off in young adulthood. The marijuana data in figure 3 illustrate this pattern. Current use of

drugs, as measured by past 30 day prevalence, follows a similar pattern except

that it tends to become lower as people move into young adulthood. Lifetime

prevalence of solvent use has a peculiar pattern in that it peaks around age 13

and then drops off.

If a sample remains intact over a period of time, the lifetime prevalence

should never decrease as age increases. A person may stop using a drug, but

when asked whether they had ever used it, the answer should always be “yes,”

even though that use may have taken place many years before. Something

unusual, then, must be happening with solvents. One possibility is that with

school-based surveys, many of those younger students who admitted to solvent use are no longer around by the upper high school years and thus are not

surveyed—that is, they have dropped out of school. This seems plausible

20
Figure 3. Lifetime prevalence by grade for inhalants and marijuana
since a great deal of research has shown that solvent abusers are a fairly dysfunctional group with a wide range of psychological and social problems that

would include poor school adjustment and dropping out. (See Oetting and

Webb in this volume.) Our laboratory has preliminary data which suggest

that the dropout phenomenon is significant in accounting for the unusual lifetime prevalence pattern. In a project to assess drug use among school

dropouts, we found that they have rates of solvent use much higher than two

control groups. In this large-scale study, dropouts reported lifetime prevalence of 41 percent, while an in-school group defined as being at high risk of

dropping out reported rates of 40 percent and the “normal” control group of

students not at risk reported a rate of only 21 percent.

Another possible explanation for the dropoff in lifetime prevalence has to do

with the differential perception of solvents by older and younger adolescents.

Solvents may be seen as “kid” drugs, and older students who have had experience with other, more socially accepted, drugs may be unwilling to admit to

the use of solvents—i.e., this is not seen as “sophisticated” behavior. A related

factor may be the relative salience of solvent use at different age levels. An

eighth grader who has recently had an episode or two of solvent use may have

a clear memory of this and perceive those incidents as drug use. Four years

later, however, the student may have totally forgotten the experience or may

dismiss it as being unimportant in the context of a drug use survey.

Regardless of the reasons for the unusual age pattern for solvent use, it has

important implications for determining the actual rates of use in a population

and for making comparisons between populations. First, if an accurate measure of total exposure to solvents is needed, the measurement should be taken

at the age of highest use; for solvents, that would be around age 13, but for

marijuana, 17 to 18 would be more appropriate. Second, if one were to compare older students in one location with younger students in another, it would

be wrong to conclude that the latter location had higher rates of solvent use

since, in fact, the reported rates would probably decrease if older students in

this group were queried.

Gender Patterns

The rates of solvent use for males and females have been converging over the

past 20 years. In 1973 Cohen estimated that 10 times more males than females were involved with solvents. In a general review of this issue several

2 2
years later, Korman (1977) put the ratio at 3:1. One of the problems in making these types of estimates is in specifying the population being assessed. For

example, it is possible that males who use inhalants are more frequently apprehended by the police than are females. Therefore, there would appear to

be a discrepancy in use rates between the genders among police-involved

youths. However, the picture in the general population is quite different. In

1988 the National High School Senior Survey reported lifetime prevalence

rates of 19.5 percent and 14 percent for males and females, respectively

(Johnston et al. 1989), while the 1988 National Household Survey of 12- to

17-year-olds reported rates of 9.2 percent and 8.3 percent (National

Household Survey 1990).

Similar gender patterns, with males having only slightly higher rates of use

were confirmed in large-scale surveys conducted in New York State (Frank et

al. 1988) and in Texas (Fredlund et al. 1989). Interestingly, the ratio of males

to females among the older National Household Survey group (i.e., 18- to 25-

year-olds) was higher for all prevalence categories at nearly 2:1, suggesting

that males continue use into adulthood much more than females.

One of the most comprehensive surveys of Hispanics, the HHANES survey

(NIDA 1987), has shown that Mexican-American males are three times more

likely than females to use solvents at any level and Cuban American males

twice as likely. Rates for Hispanics in general are lower than those for

Anglos.

In a study of American Indian adolescents, Beauvais, Oetting, and Edwards

(1985) found nearly identical lifetime prevalence rates for males and females

(31.8 percent vs. 32.9 percent) but surprisingly higher 30-day prevalence rates

for females (9.1 percent vs. 7.6 percent).

The literature contains no data on gender differences for other United States

ethnic groups. While the data from other countries are generally too sparse

to interpret gender patterns, there is a tendency toward slightly higher use

among males (Navaratnam, V.; Edmonson, K.; Smart, R.G.; Medina-Mora,

E.; and Uchtenhagen, A.: Epidemiology section in Arif et al. 1988).

In general, it appears that females experience a little more protection from

the use of solvents. This is consistent with the conclusion by Johnston and his

colleagues with respect to drug use in general among U.S. adolescents and

young adults: “Males are more likely to use most illicit drugs, and the

23
differences tend to be largest at the higher frequency levels” (1989, p. 11).

However, they go on to say, “Insofar as there have been differential trends for

the two sexes among any of these populations, they have been in the direction

of a diminution of differences between the sexes” (p. 11).

Use of Other Drugs

It is common for volatile solvent users at any age or of any pattern of use to

also use other drugs (Edeh 1989; Oetting et al. 1988, Crites and Schuckitt

1979). Exclusive use of solvents is rare. Young children who begin to use

volatile solvents will also start experimenting with other drugs, usually alcohol

and marijuana. Adolescent solvent abusers are typically polydrug users and

are prone to use whatever is available, although they do show a preference for

solvents. Adult solvent abusers also use a variety of chemicals although their

tendency is to concentrate on volatile solvents and alcohol. There is some

evidence that many adult users of heroin were once heavy solvent users, which

is further confirmation that solvent abusers represent a particularly deviant

group (D’Amanda et al. 1977). Little is known about adult patterns, and a

great deal more research is necessary before they can be accurately

characterized.

Trends in Solvent Use Prevalence Rates

There are only a few places where rates of solvent use have been accurately

tracked over time, and by far the majority of studies have focused on adolescents. Although there seems to be general agreement that rates have increased worldwide over the past 20 years, the evidence for this is mostly anecdotal and may, in part, be a function of increased awareness and detection. In

looking at the various studies, the lack of clarity of definition discussed above

must be kept in mind.

United States

The most complete record at a national level comes from the National High

School Senior Survey in the United States, which has been in progress since

1975 (Johnston et al. 1991; Most forms of drug use decline, NIDA 1992a).

Figure 4 shows the results for lifetime and past 30-day prevalence of solvent

use for U.S. high school seniors since 1976. In both categories, use has been

24
Figure 4. Trends in lifetime prevalence (ever used) and use in past 30 days of volatile solvents for high

school seniors in the United States
gradually increasing, although there is some indication that the rates may

have leveled off in the past 2 years. The number of students using currently

(i.e., within the past 30 days) is not exceptionally high. The 2.4 percent 30-day

solvent rate for 1991 compares with 54.0 percent for alcohol, 13.8 percent for

marijuana, and 1.4 percent for cocaine.

The pattern of increasing use of solvents is confirmed in a series of studies by

Frank et a1. (1988) in New York State and Fredlund et al. (1989) in Texas.

Since 1975, Frank et al. have found a quadrupling of solvent use rates (both

lifetime and 30-day prevalence) among the State’s high school students, while

even more dramatic increases were found in the Texas study.

It is important to recognize that the trend toward the increasing use of solvents in school populations is in sharp contrast to the trends for other drugs.

The National High School Senior Survey has shown substantial reductions in

both lifetime and 30-day prevalence for nearly all drugs of abuse since 1981.

It is quite possible that with increasing sanctions for other drugs and the relative lack of attention paid to solvents, youths are substituting solvents for

other drugs.

The National High School Senior Survey results do not provide data for

youths who are not in school or for younger children. Data are available for

these groups in the United States from the biennial National Household

Survey on Drug Use given since 1972 (NIDA 1990, 1991, 1992b; USDHHS

press release 1990). The lifetime and 30-day prevalence rates are shown in

figure 5. The pattern here is for increasing use through 1979, with essentially

unchanged levels since then. The lifetime prevalence rates have been around

8 percent for the past decade. These results are not directly comparable with

the National High School Senior Survey due to methodological differences;

however, they show about the same order of magnitude of use. The lower

rates for the National Household Survey are expected since these data are

averaged for all 12- to 17-year-olds. It appears from both sets of data that a

plateau in lifetime prevalence may have been reached, although it will take a

couple of more years with the senior data to be more certain.

The peculiar age pattern for solvents, with higher use being reported at the

younger ages, is not found in the National Household Survey. This survey reports data for four separate age groups, 12-17, 18-25, 26-34, and over 34. The

lifetime prevalence rates for these groups in the 1988 survey were 8.8

26
Figure 5. Trends in lifetime prevalence (ever used) and use in past 30 days of volatile solvents for 12-

to 17-year-olds in the United States
percent, 12.5 percent, 9.8 percent and 1.8 percent respectively. Thirty-day

prevalence rates showed the same pattern. These data suggest a pattern similar to other drugs, with peak rates in the young adult groups. However, it

must be kept in mind that the National Household Survey includes dropouts

who likely have higher rates of use, and perhaps equally important, the solvent question specifically includes nitrites. The latter drugs have an older age

of first use and may well be inflating the volatile solvent figures at the older

ages. Once again, the lack of clarity in the definition of inhalants creates difficulties in interpretation of trends.

Minority Populations (United States)

Table 2 presents the lifetime prevalence rates of solvent use among minority

U.S. high school seniors. While the table shows only lifetime prevalence

rates, this statistic is the most stable across different surveys and allows an accurate comparison among groups. The Black American and Anglo samples

are from the National High School Senior Survey (Johnston et al. 1987) while

the two Hispanic-American samples and the American Indian samples are

from two NIDA-sponsored projects currently in progress (Oetting and

Beauvais 1990). The Indian and Hispanic-American studies are comprehensive for these groups and represent a highly reliable estimate of use in these

populations. In the western Hispanic samples, the students were allowed to

list their own ethnicity, with the majority calling themselves Mexican

American and the others, Spanish American. A good part of this distinction

comes from a historical pattern in which a subsample of the Hispanic people

of the Southwest trace their heritage back several centuries to the original settlers of this region. These settlers came directly from Spain; thus they refer to

themselves as Spanish-American. The more recent Hispanic-Americans of

the area arrived from Mexico.

Table 2. Lifetime Prevalence of Solvent Use in Minority Populations

African American

Anglo American Indian

(N=11,713) (N=1,649) (N=325)

17% 8 % 17%

Mexican

American

(N=1,512)

12%

Spanish

American

(N=446)

16%

28
The highest rates of solvent use occured among Anglo and American Indian

seniors, with the lowest rates found among blacks. The rates for MexicanAmerican youths were in between. This was the same basic pattern found in

New York State (Frank et al. 1988) and Texas (Fredlund et al. 1989). While

data on current use, that is use within the past 30 days, are not available, it is

likely that these rates would occur in the same relative order among the

various ethnic groups.

These findings are at variance with the commonly held belief that minority

youths, particularly Mexican Americans, are at exceptionally high risk for solvent use. Since the data in table 2 are taken from school-based surveys, they

are vulnerable to bias from excluding school dropouts. On the assumption

that minorities have higher school dropout rates, we might expect that rates

for these populations might be higher than those in table 2, and perhaps even

higher than for Anglos. Arguing in favor of the lower rates for Hispanics,

however, are data from the National Household Survey (1987) showing that

Hispanic Americans at all ages had lower rates than Anglos and the

HHANES survey (NIDA 1987) showing that Mexican Americans, specifically,

had lower rates. The National Household Survey also confirmed the low rates

for blacks.

Table 2 also shows the importance of accurately defining minority groups and

not aggregating populations that may show important differences. Note the

difference in prevalence rates for Mexican-American and Spanish-American

seniors. Spanish Americans are very similar to their Anglo counterparts in

contrast to the lower rates for Mexican Americans. If these two populations

had been aggregated under the label “Hispanic American,” potentially important information would have been lost. The significance of this pattern is unclear at this point, but the higher rates of use for Spanish Americans may well

be related to their longer tenure in the United States, during which they have

become more integrated into the Anglo culture and have adopted many of the

behaviors, including similar rates of drug use. In fact, when all drugs are considered, Spanish-American youths are very similar in pattern to Anglo youths,

whereas Mexican American youths show lower rates.

The picture for American Indians is different. While table 2 shows similar

rates for Indian and Anglo seniors, other data show that Indian youths at

other grade levels have much higher rates of solvent use. Beauvais et al.

(1985) reported that 12- to 18-year-old Indian students had rates of solvent

29
use three times higher than those found for Anglo youths in the National

Household Survey. This, however, was not the best comparison, since the

methodology of the two surveys was quite different. More recent data are

available that compare the two groups on similar surveys conducted in

schools. (These are unpublished preliminary results from our ongoing studies.) These rates by grade are reported in table 3; it is clear that the Indian

students at all grades are reporting higher lifetime prevalence rates. It is quite

possible that the discrepancies for Indian youths between tables 2 and 3 are a

function of higher school dropout rates among Indian youths.

Smart (1988) examined the available evidence regarding solvent use among

Canadian Indians, and while use varied greatly from one community to the

next, many Canadian Native bands appear to have a significant problem. In a

number of instances, surveys of youths revealed that 50 percent or more could

be classified as current sniffers. In examining the differences in conditions

among the various communities, Smart concluded that the high rates were associated with extremely poor socioeconomic conditions and a very rapid rate

of cultural change.

In summary, it appears that the findings of higher rates of solvent use for

Hispanic Americans do not hold up when general population surveys are

done, but that, indeed, Indian youths are more vulnerable to the use of solvents. One can only speculate on the reasons, but they may well be related to

socioeconomic factors, which have been shown to influence the levels of solvent use in a population. (See Oetting and Webb in this volume for a discussion of these factors.) The previous studies on Hispanic Americans,

Table 3. Lifetime prevalence of solvent use by grade for American Indian

and Anglo youths in U.S. schools.

Grade in School

7 8 9 10 11 12

Indian 22.2 31.0 25.8 20.6 20.2 16.6

Anglo 14.9 18.8 18.0 16.9 15.9 14.9

30
showing high rates of use (e.g., Padilla et al. 1979) were conducted in impoverished areas where there was a great deal of social dysfunction. Not all

Hispanic youths live in disadvantaged environments, and thus, as a group, are

not subjected to the types of conditions that spawn the use of solvents. Indian

populations, on the other hand, are more generally disadvantaged and may

thus have higher rates of solvent use. Black youths appear to have the lowest

rates of use while data on other United States minorities are too sparse to

draw strong conclusions.

Trends in Other Countries

Three Canadian studies show possibly conflicting trends; however, they cover

three different periods and were conducted in separate provinces (Smart

1988). One of the two earlier studies, covering 1970 to 1982, showed significant increases among 8th to 12th graders, while the other study during approximately the same time showed little or no increase. The most comprehensive study of this age group, although restricted to Ontario province, revealed some variance from year to year since 1977 in solvent use, but with a

generally decreasing pattern. The annual prevalence rates were in the range

of 2 percent to 5 percent.

Medina-Mora and Ortiz (1988) reported on more than two dozen studies

done in Mexico since 1972 that covered general population, school, and special population samples (e.g., youths in treatment, street youths). The

methodological differences make comparisons difficult, but it is evident that

solvent use is quite low among school youths but exceptionally high among

treatment and special populations and that use has increased since 1972.

Given that only a minority of adolescents attend school in Mexico, and that

most youths are at high risk, the authors concluded, “Solvent use is the main

drug problem in Mexico” (p.166).

Research in the remainder of Latin America is quite disparate, making comparisons and the assessment of trends difficult. A review by Medina-Mora

(1988) led to conclusions similar to those found in Mexico, with the higher

rates of solvent use, by far, found among street and special populations.

These conclusions were strongly mirrored in two studies in Brazil (CarliniCotrim and Carlini 1988a, 1988b). In the first of these studies, a sample of

low socioeconomic students had solvent use rates of 24 percent for lifetime

use and 5 percent for the past 30 days. The second study was of destitute

31
street youths, and the lifetime and 30-day rates for this group were 78 percent

and 58 percent. Most importantly, nearly one third of these youths reported

daily use.

The Latin American studies illustrate the difficulty in making sense of worldwide patterns and trends in solvent use. The age groups that are surveyed vary

widely, the surveys themselves are not comparable, and the socioeconomic

conditions of the groups studied are quite diverse.

Outside the Americas, the data become even more difficult to compare.

Ramsey et al. (1989) reviewed a number of survey studies in the United

Kingdom and concluded:

Though it is generally acknowledged that the practice waxes

and wanes in any particular area, it seems safe to conclude that

somewhere between 3.5 and 10 percent of young people in the

UK have at least experimented with VSA and that current

users comprise some 0.5-1 percent of the secondary school

population. (p. 262)

Although the survey data give no indication of trends in use, Ramsey et al. reported a dramatic increase in deaths due to solvent abuse. The numbers

ranged from 2 deaths in 1971 to 111 deaths in 1987. It is unclear, however,

how much of this increase is due to more accurate detection and increased

reporting.

Data from Europe are usually limited to local studies, although there is some

indication of a moderate epidemic of use in northern Europe in the 1960s and

1970s that has since subsided (Uchtenhagen 1988). A recent review, however,

hints at another slight upsurge (Vaille 1988). In Southern Europe the rates

have been extremely low, with one report from Spain showing a 0.11 percent

30-day prevalence rate for school children (Alvarez et al. 1989).

With the exception of Australia, where the pattern of use compares with

Western industrialized countries, the use of volatile solvents in other parts of

the world is a relatively new phenomenon (Navaratnam 1988). Use continues

to be particularly troublesome among Australian aborigines, and there may be

an emerging problem in Japan, where 40,000 arrests per year are recorded for

solvent-related offenses (Tamura 1989).

32
If any sense can be made of the international scene, it is that solvent use became known in the early 1970s and appears to be increasing (with the exception of Europe). Most use occurs among children and adolescents, local epidemics are common, and solvents are typically between the third and fifth

most common drug used by youths (Arif et al. 1988).

Solvent Use Among Adults

Although solvent use is generally seen as an adolescent phenomena, it must

be recognized that some use extends into adulthood (Hershey 1982; Streicher

et al. 1981). In the United States, the National Household Survey reports

fairly high lifetime prevalence rates in the 18- to 34-year-old range, but current use in this group is very low at around 0.5 percent (National Household

Survey 1990). It is generally felt that solvent use in adulthood is indicative of

highly dysfunctional individuals and occurs when other drugs are not available. There are also anecdotal reports of isolated instances in which groups of

adults have developed a pattern of solvent use that is extremely heavy and

seems to have become endemic in that population. Adult use of solvents is an

extremely underresearched problem and is deserving of much more attention.

The highly deviant nature of these groups and their marginal living arrangements will make this work difficult.

The other adult pattern of solvent use occurs in industry, where workers come

into contact with a wide range of commercial solvents (Parker 1989). Most of

the concern in industrial settings is for workers who are inadvertently exposed

to solvents, but it is also recognized that a small percentage of workers will

seek out opportunities for inhaling chemicals in doses far above what is normally present in the work setting. It is likely that these people are also involved with other drugs and see this as one more opportunity for intoxication.

Conclusions And Recommendations

The state of knowledge regarding the epidemiology of volatile solvent use lags

behind that of other drugs. This in part stems from lack of clarity in the definition of what are usually referred to as “inhalants.” Another reason for the

sparsity of data may lie in the relatively low rates of volatile solvent use when

compared to other drugs, leading most researchers to focus on drugs with

higher prevalence patterns. Other chapters in this volume describe the high

levels and wide range of dysfunction found among volatile solvent abusers,

3 3
and it may well be that the research community would rather concentrate on

populations with a higher probability for reduction in drug use. Solvents lack

the glamour of other drugs and do not get the attention in the papers and

news magazines afforded drugs such as crack, leaving many researchers reluctant to work in the backwaters of drug abuse.

The following recommendations derive from an assessment of the current

state of research and the clear need for more precise data.

Long-term surveillance is needed to detect and monitor trends and

patterns of volatile solvent use and abuse.

While long-term trend data may be available for certain general populations,

subpopulations may have different, and important, trends and patterns that

indicate a need for special interventions and investigation. For instance,

there is a strong indication that school dropouts and certain socioeconomic

status groups are at high risk for volatile substance abuse.

Surveillance systems, other than general population surveys, are needed to assess the levels of solvent abuse in high-risk groups. It is well known that

volatile substance abuse is more prevalent in marginal groups, which may not

be easily accessible by the usual methods of field research. For example,

monitoring emergency room admissions in public hospitals could give a more

accurate picture of volatile substance abuse in a population. Alternately, longitudinal studies of potential school dropouts (i.e., those experiencing academic problems early in school) could be useful in determining the pattern of

onset of volatile substance abuse.

It should be noted that basic epidemiology is the starting point for further investigative studies (see Oetting and Webb, this volume), and without this type

of data for both general and special populations, it is difficult to establish a

meaningful research agenda. Solid epidemiological data would also help focus attention on solvent abuse, leading to increased resources for further

studies and interventions.

Cross-national and cross-cultural studies, using comparable methodologies, would be useful in detecting conditions leading to use or nonuse of

solvents.

It is clear that there are countries, or regions, of the world, in which solvent

use is rare or may be declining. Analysis of the socioeconomic, political, or

34
other population variables in these locations could reveal factors that protect

people from the use of solvents. The need for methodological consistency is

obvious.

Studies of minority or ethnic populations should be designed to avoid broad

labels that may obscure important differences among subgroups. For instance, in studies of Hispanic populations in the United States, it is important

to distinguish between Mexican Americans, Spanish Americans, Cubans,

Puerto Ricans, and other Latinos from Central and South America. Existing

data show that there are significant differences between these groups in drug

use behavior. Cognizance of these types of distinctions will lead to more

precise and usable information.

A common terminology is needed for what is meant by “inhalant abuse.”

The lack of such conventions has hampered research in this field and has led

to conflicting findings. It is recommended that the term “volatile substance

abuse” be reserved for abuse of industrial solvents, or alternately, substances

containing volatile hydrocarbons and that the use of other substances that are

inhaled be excluded from this category (e.g., nitrites, anesthetics, and powdered stimulants that are used intranasally). The term “volatile solvent use”

should be used for less serious patterns that do not lead to physiological or

behavioral problems (e.g., patterns of experimentation or brief episodic use).

More information is needed on the nature of episodic outbreaks of solvent

use.

Although the majority of users during these outbreaks are not at risk, little is

known about the possible effect on vulnerable individuals. Do outbreaks lead

to volatile substance abuse for certain people where it otherwise would not

have occurred? What are the dynamics of episodic patterns? How is knowledge of use and use itself transmitted? Does publicizing an outbreak lead to

more widespread use? How can outbreaks be managed without exacerbation

of the problem?

What types of solvents are most commonly used?

Current research does not adequately assess the preference for different types

of solvents. Knowledge in this regard could be helpful in determining the

motivations to use solvents and could also be used to guide commercial regulation of the more popular or dangerous substances.

35
More data are needed on the economic factors associated with higher

population rates of volatile substance abuse.

The literature is very consistent in identifying poor economic conditions as

being strongly correlated with higher levels of volatile substance abuse.

However, the dimensions of poverty leading to use are unclear. Are solvents

used because they are cheap and thus more available than other drugs? Is

there a specific level of poverty associated with volatile substance abuse? Is

there less stigma attached to volatile substance abuse in poor communities by

community members? Do the law enforcement, health, and social service systems apply fewer sanctions against solvents in poorer communities? Since

volatile substance abuse can also occur at any socioeconomic level, is use in

poorer communities linked to the secondary effects of poverty, such as family

dysfunction, which can also occur at higher socioeconomic levels?

Most of the information available on prevalence rates is for adolescents.

More data on adult patterns of use are needed.

With the exception of the National Household Survey in the United States,

most of the data for adults is anecdotal, and adult use may be seriously underestimated. It is likely that adults who engage in volatile substance abuse are

highly dysfunctional and are a difficult group to access and study, thus

requiring substantial research monies.

Knowledge of the relationship between levels of volatile substance abuse

and social policy would be useful in assessing potential deterrents.

There is little consistency in national, State, and local laws regarding the use

or sale of volatile solvents. While this may be an unfortunate situation in

some respects, it does present the opportunity to study prevalence rates under

various legal conditions. This may help in establishing policy consistent with

lower levels of use.

The distinct age pattern displayed by solvent use needs a more complete

exploration.

Several explanations have been presented for why solvent use peaks at an earlier age than other drugs of abuse. However, these explanations are speculative and require more study. This is an instance where comparative studies

across different populations could be useful, since age of onset is probably

related to varying patterns of social control.

36
designing more precise epidemiological studies.

Ethnographic studies of volatile solvent abusers would be helpful in

Volatile solvent abuse is characterized by a number of anomalies when compared to other drugs of abuse. In particular, heavy users appear to be highly

alienated from society, making a good deal of information inaccessible.

Knowledge of their values, beliefs, routines, and the consequences of their

solvent use would be valuable information in conducting accurate epidemiological studies.

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Carlini-Cotrim, B., and Carlini, E. The use of solvents and other drugs among

children and adolescents from a low socioeconomic background in Sao

Paulo, Brazil. Int J Addict 23:1145-1156, 1988a.

Carlini-Cotrim, B., and Carlini, E. The use of solvents and other drugs among

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Cohen, S. The volatile solvents. Public Health Rev 2:185-214, 1973.

Crites, J., and Schuckit, M. Solvent misuse in adolescents at a community

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D’Amanda, C.; Plumg, M.; and Taintor, Z. Heroin addicts with a history of

glue sniffing: A deviant group within a deviant group. Int J Addict

12:255-270, 1977.

Edeh, J. Volatile substance abuse in relation to alcohol and illicit drugs:

Psychological perspectives. Hum Toxicol 8:313-317, 1989.

Edsondson, K. Review of the extent of volatile solvent abuse in Australia. In:

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Frank, B.; Marel, R.; and Schmeidler, J. The continuing problem of youthful

solvent abuse in New York State. In: Crider, R., and Rouse, B., eds.

Epidemiology of Inhalant Abuse: An Update. Research Monograph 85.

DHHS Pub. No. (ADM)88-1577. Rockville, MD: National Institute on

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41
Acknowledgment

Preparation of this manuscript was supported in part by funds from the

National Institute on Drug Abuse (Grant Nos. R01 DA-03371 and P50 DA

07074).

Author

Fred Beauvais, Ph. D.

Department of Psychology

C-78 Clark Building

Colorado State University

Fort Collins, CO 80523

42
Epidemiology of Volatile

Solvent Abuse:

The Texas Experience

Eric V. Fredlund

Beauvais’ synthesis of the epidemiology of volatile substance abuse highlights

two conceptual distinctions critical for understanding patterns of inhalant use.

The first differentiates volatile solvent abuse from that of nitrites and anesthetic gases. The second distinguishes acute volatile solvent abusers and

chronic volatile solvent abusers.

Beauvais argues that it is a mistake to lump volatile solvent abuse and nitrite

abuse in a single category, inhalant abuse. The two groups of substances have

disparate pharmacological properties and are used by people with dissimilar

socio-demographic characteristics and motivations. One of the primary goals

of epidemiological research is to understand the process of substance abuse.

When pharmacological characteristics, social settings, demographics, and

motivations are different, the underlying process is also likely to be different.

Yet the two primary sources of national information on substance use (the

National High School Senior Drug Abuse Survey [Johnson et al. 1991] and

the National Household Survey on Drug Abuse [NIDA 1992]) report a

prevalence of inhalant use that subsumes volatile solvent abuse, nitrite abuse

and anesthetic gas abuse.

The reporting protocols used in these surveys have tremendous influence on

the choices made by investigators who research the epidemiology of substance

43
use. When we designed the Texas School Survey in 1988 (Fredlund et al.

1989), the first question asked was, “How can we produce information comparable to national data?” Such comparability was a consideration at every stage

of the survey process from the selection of questions through protocols,

including the decision to report the prevalence of inhalant use. Fortunately,

the use of several additional questions enabled the differentiation of volatile

solvent abuse from nitrite abuse.

These Texas School Survey results clearly illustrate that students who primarily use volatile solvents are different from those who use nitrites. In 1988,

younger students were more likely to report experience with volatile solvents

than older students, and older students were more likely to report experience

with nitrites than younger students (figure 1). Very few students reported experience with both volatile solvents and nitrites, which established that different substances tend to be used by students at distinct periods in their development. Moreover, similar age patterns of use were reported in 1990 (1990

Texas School Survey), building the case that these age patterns of use tend to

persist through time.

One justification for combining nitrite use and solvent use under a single

taxon might be that the users themselves call both these respective activities

inhalant use. If this is true, one might argue that it is convenient to ask questions about inhalant use because the number of products that can be abused

by sniffing (inhaling through the nose) or huffing (inhaling through the

mouth) is very large. It is not practical to ask questions about every abused

product. However, many who sniff or huff chemical substances for purposes

of getting high have no idea they are using inhalants.

The 1990 Texas School Surveys included questions about the following substances students sometimes sniff or huff to get high:

Liquid or spray paint

Correction fluid or liquid paper

Gasoline

Freon

Shoe shine, Texas Shine

Glue

Paint thinner, toluene, other solvents

Other sprays (Pam, hair spray, etc.)

44
Figure 1. Lifetime prevalance of use of nitrites, correction fluid, glue, and

paint by grade of respondent: The 1988 Texas school survey

45
Poppers, Locker Room, Rush, Medusa,

or whippets

Other inhalants

The question included an explanation that huffing or sniffing these things for

purposes of getting high is called inhalant use. In 1990, 24 percent of seventh

graders admitted using one or more of the substances listed above. Yet of the

self-admitted users, one-half denied ever using inhalants when a general question about inhalant use was asked on the next page of the survey. The term

“inhalant” is apparently not part of the lexicon of a significant proportion of

those who abuse such substances.

These observations and experiences lead me to endorse Beauvais’ call for a

common definition of inhalant use, one that explicitly differentiates volatile

solvent abuse from nitrite abuse. But in doing so, we must be careful not to

throw out the baby, with the bath water. A significant number of individuals

use nitrites and, regardless of whether or not we call them inhalant users, they

are still a legitimate topic of epidemiological inquiry.

Volatile Solvent Users and Volatile Solvent Abusers

Beauvais distinguishes two groups of volatile solvent abusers on the basis of

acute or chronic patterns of use. These groups have dissimilar demographic

and social characteristics and manifest themselves in different ways. Different

research questions are associated with each group. School surveys can be

used to investigate acute volatile substance abusers, but this contributes little

to the understanding of chronic solvent abusers.

The most common numerically are the acute abusers. They are usually young

(13 or 14 years of age) and are experimenting infrequently with a variety of

different industrial solvents. A surprisingly large percentage of youths may

engage in this pattern of behavior. In the 1988 Texas School Survey

(Fredlund et al. 1989), 22 percent of the seventh graders admitted sniffing

correction fluid to get high, 11 percent used glue, 10 percent tried paint, and 8

percent used solvents and thinners. Additionally included in this reported

lifetime inhalant use by seventh graders, an average of 4 (out of the list of 10)

different inhalants were tried over a total of 18 different occasions.

46
Beauvais observes that outbreaks of acute volatile solvent abuse can be

episodic. Marked short-term changes in the prevalence of inhalant use among

Texas secondary students between 1988 and 1990 illustrate this point.

Overall, the percentage of secondary students who huffed or sniffed any substance within the school year decreased from 19 percent in 1988 to only 12

percent by 1990 (TCADA 1990). Reported lifetime use of volatile solvents

over all grades decreased between the 2 years with a corresponding diminution in the number of different volatile solvents used.

Beauvais also presents preliminary data associating early volatile substance

abuse with an increased risk of dropping out of school. Again, the 1988 Texas

School Survey data are consistent with these conclusions. For example, in

both 1988 and 1990 surveys, volatile solvent-abusing youth had many characteristics associated with dropping out: poor academic achievement, high rates

of truancy, and an excess of disciplinary problems. The survey results also

consistently supported several other of Beauvais’ observations about acute

volatile solvent abuse, including patterns of use by race-ethnicity and gender.

The association between inhalant use and generally at-risk youth is also apparent from a 1989 survey of youth entering the Texas Youth Commission

(Fredlund et al. 1990a). Of these youths, 39 percent admitted lifetime use of

inhalants, while 23 percent admitted use in the past month. These rates are

approximately twice as high as those reported by Texas secondary students in

1988 (controlling for age, gender, and race-ethnicity).

According to Beauvais, relatively few individuals continue to use solvents into

adulthood. Texas survey data generally support this observation. Less than

0.5 percent of Texas household adults reported current use of inhalants

(Spence et al. 1989). Most adults who admitted current inhalant use reportedly used nitrites; use of volatile solvents was very rare. However, 27 percent

of inmates entering the Texas Department of Corrections prison system

(Fredlund et al. 1990b) reported a lifetime experience with such substances.

Recommendations for Research

Beauvais makes several important suggestions for future research in the epidemiology of inhalant use. Several are methodological and based on the observation that a plethora of substances are sniffed or huffed in order to

achieve intoxication. While epidemiologists refer to substances taken in this

47
way as “inhalants” or “volatile solvents,” those engaging in such behaviors are

often unfamiliar with these terms. Ethnographic research is suggested as a

source of basic information for constructing survey questions relevant to

patterns of inhalant use.

Ethnographic research also has a potential role for helping us to understand

the process that underlies geographic, demographic, and cultural diversity in

patterns of inhalant use. Beauvais describes large differences among local

communities and race-ethnic and age groups with respect to the incidence and

prevalence of inhalant use. Moreover, patterns of inhalant use change rapidly

as compared to other drugs. While epidemiological studies document differences in patterns of use among groups and rapid change in patterns of use

through time, they contribute little with respect to understanding these

patterns of difference and change.

Inhalant research is also needed to measure the risks associated with acute

volatile solvent abuse—dropping out of school, subsequent illicit drug use,

subsequent legal involvement, and progressing to a chronic pattern of inhalant use. What, if anything, is the significance of experimenting with

volatile substances a few times at a young age? In areas where early experimentation with inhalants is common, the answer to this question has profound social and policy implications as well as scientific interest.

References

Fredlund, E.; Spence, R.; and Maxwell, J. Substance Use Among Students in

Texas Secondary Schools. Austin, Texas: Texas Commission on Alcohol

and Drug Abuse, 1989.

Fredlund, E.; Spence, R.; Maxwell, J.; and Kavinsky, J. Substance Use Among

Youth Entering Texas Youth Commission Reception Facilities. Austin,

Texas: Texas Commission on Alcohol and Drug Abuse, 1990a.

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Texas Department of Corrections Inmates, 1988. Austin, Texas: Texas

Commission on Alcohol and Drug Abuse, 1990b.

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48
Pub. No. (ADM)91-1835. Rockville, MD: National Institute on Drug

Abuse, 1991.

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Population Estimates 1991. DHHS Pub. No. (ADM)92-1887. Rockville,

MD: National Institute on Drug Abuse, 1992.

Spence, R.; Fredlund, E.; and Maxwell, J. 1988 Texas Survey of Substance Use

Among Adults Austin, Texas: Texas Commission on Alcohol and Drug

Abuse, 1989.

TCADA, The Texas Commission on Alcohol and Drug Abuse. 1990 Texas

School Survey. Austin, Texas: Texas Commission on Alcohol and Drug

Abuse, 1990.

Author

Eric Fredlund, Ph.D.

Texas Commission on Alcohol and Drug Abuse

720 Brazos, Suite 403

Austin, TX 78701

49

Epidemiology of

Inhalant Abuse:

A Canadian View

Reginald G. Smart

A review of the epidemiological literature on solvent or inhalant abuse is difficult, based on the limited subject matter. Special studies of solvent abusers

are not usually available. The ones that are may be small, highly specialized,

and based on a few cases for which results are difficult to generalize. Solvents

and inhalants are included in a few large monitoring studies such as the

National Institute on Drug Abuse National High School Senior Survey and the

National Household Survey (e.g., Johnston et al. 1991; NIDA 1992). In

Canada we include solvents at the school level but not in the household studies. When solvents are included in monitoring studies, usually relatively few

relevant questions are posed or solvents are clearly not the focus of the research. It is also difficult to understand whether the category “solvents” includes the same substances in all studies. The chapter by Beauvais makes a

good case for increasing our level of knowledge of solvents and outlines many

of the important issues. I will add to the research agenda proposed and present a few different perspectives.

From my viewpoint, it is desirable to have more information along the

following lines:

A better definition of “solvent-inhalants”

A standardization of solvent questions on surveys

51
Studies of users’ perceptions of solvent’s effects

More studies of high-risk populations of youths and adults

More clinical epidemiology

More studies of the natural history of solvent use

More studies from other countries

Problems of Definition

The area of solvent-inhalants is a confused one. The concepts of solvents and

inhalants are both too broad. The concepts could be narrowed by disaggregating and identifying all of the drugs and substances included; this may make

for very long lists of individual products. Such lists would not be acceptable in

many surveys if we attempted to get a use/nonuse response for each drug. It

would be possible to differentiate the category into anesthetic gases, nitrites,

and solvent-inhalants. Probably only the latter category is needed in most

studies of youth, although nitrites may be necessary in some places.

It would also be of interest to know whether users see differences in the effects for the various solvent-inhalants, e.g., gasoline, glue, paint thinner. In

our data from students, it is clear that glue users also use solvents. However,

we do not make any effort to see whether users see any different effects from

one substance or the other. Users seem to have definite preferences for some

inhalants and not others but we know little about this area. If they view all as

having the same effects, that would mean that they could be aggregated into

the same question.

Standardization of Solvent-Inhalant Questions

Only a few surveys regularly ask about solvent-inhalant use in North America.

Most of this research is supported by NIDA and a limited number of States.

It should be possible to standardize the solvent-inhalant questions for most

surveys and special studies. If this standardization occurred, it would be easier to rule out the possibility that students responded to the inhalant question

by including crack or nitrites or anesthetic gases. This would also make trends

easier to interpret. An assembly of researchers could propose a standard

nomenclature and a standard set of questions for solvent-inhalants. Unless

this is done by reputable scientific leaders or agencies, it would probably be

52
ignored by those doing the research. Also, it would be necessary for funding

agencies to set standards on the use of some of these solvent questions

wherever possible.

Users’ Perception of Solvent-Inhalants

Unlike some abused substances, solvent-inhalants have never been very fashionable. Other abused substances have some sort of status or prestige.

Hallucinogenic drugs and even cannabis are associated with mind expansion,

enhanced perception, or various protest movements. Cocaine promises, according to some users, to be the champagne of drugs and to enhance sexual

activities. However, solvent-inhalant abused substances have no mystique, no

cachet, and they have never become “smart” or stylish. No one extols their

virtues publicly, and yet they continue to be used by a number of young people

and adults. It would help to understand solvent-inhalant use if we knew more

about the perception of these drugs among users, such as the status that they

have, the beneficial effects that users expect, and the health risks that they see

from light and heavy use and from different products. Some psychologically

perceived beneficial effects must be experienced for solvents to continue to be

used. In our student study (Smart and Adlaf 1989), 13.7 percent of solventinhalant users who preferred glue inhaled the glue’s vapors 40 or more times

in the past year. This is much higher than for cannabis (9.7 percent), nonmedical barbiturates, stimulants, or tranquilizers (2.7 percent to 5.3 percent),

LSD (3.5 percent), or cocaine (7.8 percent). Glue users were much more

likely to be heavy users than were users of other solvents (6.4 percent vs. 13.7

percent).

Because of the relatively low status of solvent-inhalants, some users may tend

not to report use of this substance on surveys. In our own student study, the

nonresponse rate for the glue and solvent questions was rather high relative

to most other abused substances (1.5 percent and 1.4 percent compared to a

mean of about 0.8 percent). However, the retest correlations for the solvents

(and glues) question was very high. Nonreporting of the limited glue and solvent use may be greater among adults than young people, especially for recent

use. Inhalant use is disapproved of in adult society but not always among

youths.

53
Solvent-Inhalant Use in High-Risk Adult

and Young Adult Populations

In recognizing the need for more information on solvent-inhalant use by

adults, I would emphasize high-risk groups and family-based studies. General

population studies indicate that overall use rates are low, especially for recent

use (about 1 percent). However, rates of use on some Canadian Indian reservations are very high (Barnes 1979). Family patterns of solvent-inhalant use

have seldom been investigated. Some Indian reservations with poor social

and employment conditions do not seem to have the serious inhalant problems others do; the reasons for this are not well understood. Acculturation

may be one variable, but others are also likely to be important.

High-risk adult groups for solvent abuse could include the young homeless

and also skid-row populations. Most studies of the homeless that examine

solvent use appear to come from Mexico or Brazil. This youth homelessness

appears to be increasing or at least is a more recognized problem than in the

past. Estimates for the United States indicate that as many as 1.3 million

youths may become homeless at some time during the year. A recent study of

homeless youths in Hollywood, California (ages 13 to 17) showed no data on

solvent use (Robertson et al., unpublished). Our recent study of homeless

youth in Toronto found that 24 percent had used inhalants (all types combined) and about 1 percent used them daily. This is a rate 10 times as high as

for comparable youths in school. It is interesting that, in this study, about

twice as many females as males used solvents ever (35 percent vs. 18 percent)

and in the past year (25 percent and 12 percent). These data suggest that solvent-inhalant use is a serious problem for homeless youths, especially females.

We do not know why females in these groups should use more solvent-inhalants than males; further cross-tabulations are needed. This study does

suggest that solvent questions should be put in studies of the homeless and

that further study is needed to clarify the reasons for the high rates of use.

Clinical Epidemiology of Solvent-Inhalant Abusers

Most studies of solvent-inhalant abusers deal with relatively infrequent use.

General population studies and those of students usually include too few

heavy or addicted users for any serious analysis. The social and personality

characteristics of solvent-inhalant abusers appearing for treatment are not

well documented; however, solvents contribute significantly to the problems

54
among those getting drug abuse treatment. At the Addiction Research

Foundation, solvent-inhalant abusers are the primary problem for about 1

percent of approximately 4,200 patients getting treatment each year. This

may seem to be a small number; however, it is much larger than the proportions with hallucinogens, sedative-hypnotics, or amphetamines as their primary problem. Almost two-thirds of the inhalant problems arise from inhaling solvent products; about 30 percent from inhaling solvents of glue. A few

patients have problems with gasoline sniffing (from the benzene, other solvents, and additives contained therein). There is no trend toward greater solvent abuse in our treated population than in the population as a whole.

Solvent abusers in treatment are older than the alcoholics in treatment and a

greater percentage—about 80 percent—are male. Most of the solvent-abusing patients are aged 18 to 29, only a few are younger. About 10 percent are

married, living with spouses, and employed. In general, solvent-inhalant

abuse seems to occur with young, single male adults who are unemployed.

We know relatively little about the smaller, more stable population of married, employed, solvent-inhalant abusers; a further study may be of interest.

More research into clinical epidemiology might also clarify the reasons why

solvent-inhalants are chosen over the more popular drugs such as alcohol. It

is possible that these are not preferred substances but begin as stopgap measures when other substances of abuse are not available or are too expensive.

How solvent abusers progress to dependency that requires treatment is also

not understood.

Natural History of Solvent Use and Abuse

Although many people try solvent-inhalants for a short time, few continue

their use past the first few sessions. There are still many questions about why

solvent abusers stop. Probably most were only experimenting and wanted to

see what it was like. Perhaps some worried about health risks. It would be interesting to know the factors that contribute to stopping solvent use.

Beauvais has noted that use peaks and usually stops about the age of 13, but

no good explanation seems to exist for it. In our school study (Smart and

Adlaf 1989) students’ glue-and-solvents-use peaked at grade 7 (about 25-33

percent of the grade 7 level) or at the age of 12 or 13 and was lowest at the age

of 18+. Concomitant changes that we see among students between the ages

of 12 and 18 are a large increase in smoking tobacco (6.6 percent to 28.0 per55
cent), drinking alcohol (42 percent to 64.6 percent), and smoking cannabis

(0.7 percent to 12.1 percent). These are the largest changes that occur in substance use among young people. When they get to be 14 or 15, their access to

alcohol, tobacco, and cannabis increases greatly (as do their use levels) and

that may reduce interest in solvents. Perhaps interest in illicit drugs is greatly

increased around that age (tobacco and alcohol are illicit to these populations). However, physical access to drugs and peer pressure (from older

teens) probably contributes to this problem as they move from lower or primary school to high school. More understanding of how and why 13- to 15-

year-olds change their use patterns would be useful, rather than relying on

hypothetical speculation.

International Perspective on Solvent-Inhalant Use

Almost all of the studies of solvent-inhalant abuse come from six

sources—the United States, Canada, Mexico, the United Kingdom, Australia,

and Brazil. With the low cost and universal availability of solvents and inhalants, it is surprising that so few countries have reported any solvent or inhalant abuse problem. Perhaps we are wrong in thinking that such abuse does

not occur in other countries. It would be of interest to have an international

study of solvent-inhalant abuse in many countries, perhaps sponsored by the

World Health Organization or some other international body. This study

might also help to clarify some of the enigmatic aspects of solvent abuse mentioned by Beauvais and others. It should focus on levels and frequency of solvent-inhalant use, the reasons for use, effects expected from the abused substance, reasons for quitting use and reasons for progressing to heavy use as

well as use of other abused substances. This type of study could establish

whether there is any validity to the concept that solvent abuse is related on a

worldwide basis to poverty levels, low levels of acculturation among aboriginal groups, and aboriginal status. This type of study may also clarify the rates

of solvent-inhalant abuse for different types of products.

Summary

The epidemiology of solvent-inhalant abuse is still not well understood.

Problems with definition and questions about use remain. Many uncertainties

still exist about solvent-inhalant abuse by high-risk adults and youths. Also,

the clinical epidemiology of solvent abuse, especially the natural history of

56
abuse, remains to be studied. The reasons why solvent-inhalant use stops so

early is also not well understood. The origins of such abuse in poverty conditions and among aboriginal groups could be studied on an international level.

References

Barnes, G.E. Solvent abuse: a review. Int J Addict 14:1-26, 1979.

Johnston, L.; O’Malley, P.; and Bachman, J. Drug Use Among American High

School Seniors, College Students, and Young Adults, 1975-1990. DHHS

Pub. No. (ADM)91-1835. Rockville, MD: National Institute on Drug

Abuse, 1991.

National Institute on Drug Abuse. National Household Survey on Drug Abuse:

Population Estimates 1991. DHHS Pub. No. (ADM)92-1887. Rockville,

MD: National Institute on Drug Abuse, 1992.

Robertson, M.J.; Koegel, P.; and Ferguson, L. “Alcohol Use and Abuse

Among Homeless Adolescents in Hollywood.” Unpublished paper.

Alcohol Research Group, Berkeley, CA, 1990.

Smart, R.G., and Adlaf, E.M. The Ontario Student Drug Use Survey: Trends

Between 1977-1987. Toronto: Addiction Research Foundation, 1989.

Author

Reginald G. Smart, Ph.D.

Director, Prevention Studies Department

Addiction Research Foundation

33 Russell Street

Toronto, Ontario, Canada M5S2S1

57

Psychosocial Characteristics

and Their Links With Inhalants:

A Research Agenda

E. R. Oetting

Jay Webb

This chapter has two goals: (1) to assess the state of the art—to determine

what is known about the relationships between psychosocial characteristics

and inhalant use and (2) to suggest the next stages in psychosocial research.

Research Findings: The Psychosocial

Correlates of Inhalant Use

Barnes (1979) thoroughly reviewed the early inhalant literature, noting particularly high levels of use in native peoples and attributing that to acculturation stress. He also indicated that (1) inhalant users were more likely to use

other drugs, including alcohol, (2) their families were likely to be less stable,

less successful, and more alcohol or drug involved, (3) their school adjustment

may be poor, and (4) there were strong peer drug influences. The research

reported in the decade since his review has expanded on, but not greatly

altered, these conclusions.

Family Strength

One of the more frequent findings is that inhalant users have suffered from

serious family dysfunction. They are more likely to come from broken homes,

59
from families with alcohol and/or drug problems, and from families that are

marked by conflict and discord. Nearly every study that evaluated family

structure found that inhalant users were more likely to come from homes

where the primary family was not intact (Albaugh and Albaugh 1979; BerrielGonzalez et al. 1978; Carlini-Cotrim and Carlini 1988b; Crites and Schuckit

1979; Guitierrez et al. 1978; Jacobs and Ghodse 1988; Leal et al. 1978;

Massengale et al. 1963; Nurcombe et al. 1970; Schottstaedt and Bjork 1977).

The exceptions were comparisons of young inhalant users and young marijuana users on an Indian reservation (Oetting et al. 1988), young users and

nonusers in prevention programs in two Texas barrios (De Barona and

Simpson 1984), very young users and nonusers in an Indian village elementary

school (Kaufman, 1973), and low socioeconomic status (SES) users and

nonusers from a city in Brazil (Carlini-Cotrim and Carlini 1988a). In these

reports, where there were no differences in intact family structure between

inhalant users and others, the users were relatively young, and both users and

nonusers were from groups with serious socioeconomic problems. It may be

that in these situations, family breakdown was high for all groups, so inhalant

users did not stand out. It may also be that a further and more detailed examination of family intactness would have shown more subtle differences. A

study of opiate addicts in Berlin, for example, found that half of the families

of both addicts who used inhalants and those who did not were broken, but

the average age when the breakup occurred for inhalant-using addicts was

only 8-9, compared with age 14-15 for the other addicts (Altenkirch and

Kindermann 1986).

Family problems also show up in other ways. A number of studies indicate

that families of inhalant users may be marked by discord, aggression, and/or

hostility (Berriel-Gonzalez et al. 1978; Comstock 1978; Crites and Schuckit

1979; De Barona and Simpson 1984; Gilbert 1983; Korman et al. 1980;

Matthews and Korman 1981). Frank et al. (1988) asked a slightly different

question and found that the less close young people felt to their families, the

more likely they were to use inhalants.

The families of inhalant users were also more likely to be deviant in other

ways. Two studies found that more family members had prison records

(Berriel-Gonzalez et al. 1978; Jacobs and Ghodse 1988). Where family drug

or alcohol use was assessed, the families of inhalant users were more likely to

be substance involved (Albaugh and Albaugh 1979; Bachrach and Sandler

1985; Berriel-Gonzalez et al. 1978; Carlini-Cotrim and Carlini 1988a; Crites

60
and Schuckit 1979; Guitierrez et al. 1978; Smart et al. 1972; Stybel et al.

1976). In a further analysis, Bachrach and Sandler (1985) found striking differences within their sample of inhalant users as a function of whether these

individuals were from drug-using versus drug-free families. The inhalant

users with drug-using families had used more types of drugs, perceived their

friends as having a more favorable attitude toward drug use, had experienced

more poverty, and were more likely to have disrupted families and parents

who had been arrested.

Opportunity

Given the kinds of family problems that many inhalant users have, such as

criminal records, alcoholism, drug use, and broken families, all of which

should negatively influence socioeconomic status (SES), it seems surprising

that there are not large and consistent differences, with inhalant users coming

from families that are low in SES. Three studies showed no SES differences

(Gossett et al. 1971; Press and Done 1967; Stephens et al. 1978), while several others did find families of inhalant users to be lower in SES (Altenkirch

and Kindermann 1986; Berriel-Gonzalez et al. 1978; Ellison 1964; Guitierrez

et al. 1978; Korman et al. 1980; Reed and May 1984, Sokol and Robinson

1963). The lack of consistent findings in all studies may be because measures

of SES tend to be somewhat unreliable. It is more likely, however, that the

difficulty lies in the comparisons that can be made in an individual study.

Really low SES groups, for example, may be underrepresented in population

surveys or in school based surveys, and population studies, therefore, may

miss the groups lowest in SES and, possibly, highest in inhalant use. Studies

done totally within low SES populations may have the same problem. When

the majority of people involved in the study are suffering from unemployment

and lack of opportunity, it is hard for one group to be identified as having

more socioeconomic problems.

In fact, some relationship probably exists between low SES and inhalant use.

The highest rates of inhalant use, for instance, are found in barrios, in this and

in other countries, and on Indian reservations, places where unemployment,

low education, poverty, and prejudice are endemic. A study that included

both high SES and these low SES groups would almost have to show that SES

is related to inhalant use.

61
The inhalant users themselves often show problems with employment

(Berriel-Gonzalez et al. 1978; Comstock 1978; Korman et al. 1980). A seeming exception occurred in a study of low-income youths in Brazil, where more

inhalant users had jobs (Carlini-Cotrim and Carlini 1988a). This could, however, have meant that even among generally impoverished youths, the inhalant users were less involved in school and therefore more involved in jobs.

It may also have meant that they needed the jobs more.

Perhaps the most telling quote comes from an unusual study of opiate addicts

in Berlin, some of whom regularly used inhalants (Altenkirch and

Kindermann 1986). All of these subjects were addicts, but the opiate addicts

who also used inhalants could not even function well in the criminal drug

scene. Inhalant users had less illegal income and “Chronic sniffers in adulthood do not show the social agility that is necessary in order to survive in the

drug scene and procure the great amounts of money that would be needed

each day for hard drugs” (p. 103).

School

Inhalant users also have serious problems in school. Beauvais (this volume)

points out that inhalant users seem to disappear from school-based surveys

beginning with the eighth grade. One hypothesis is that they drop out. The

results of other research are strongly supportive of this hypothesis. When

compared with either nonusers or users of other drugs, inhalant users tend to

have greater difficulty in school. They are more likely to have high absenteeism, to have been suspended, to drop out, or to have been expelled

(Altenkirch and Kindermann 1986; Bachrach and Sandler 1985; BerrielGonzalez et al. 1978; Carlini-Cotrim and Carlini 1988b; Comstock 1978;

Coulehan et al. 1983; Galli 1974; Jacobs and Ghodse 1988; Matthews and

Korman 1981; Reed and May 1984; Schottstaedt and Bjork 1977; Winburn

and Hays 1974). They are also likely to have poor academic performance and

lower grades (Ackerly and Gibson 1964; Annis et al. 1971; Barker and Adams

1963; Carlini-Cotrim and Carlini 1988a; Coulehan et al. 1983; Crites and

Schuckit 1979; De Barona and Simpson 1984; Galli 1974; Guyer-Christie

1978; Kandel 1975; Korman et al. 1980, Matthews and Korman 1981;

Massengale et al. 1963; Nylander 1962; Press and Done 1967; Schottstaedt

and Bjork 1977; Smart et al. 1972; Stephens et al. 1978; Wingert and Fifield

1985). Among Australian aborigines, inhalant users showed more behavior

problems in school and may have been less able in school (Nurcombe et al.

62
1970). Frank et al. (1988), in a New York survey of school children, found

that one-third of the students in grades 7-10 who had either a “D” or an “F”

average had recently used inhalants. The consistency in these results is unusually high; whenever a study looked at school adjustment, and many studies examined this variable, the inhalant users showed higher levels of school

problems.

Deviance and Delinquency

As might be expected, since inhalant users have trouble adjusting to work and

to school, they also have trouble adjusting to society in general. Inhalant use

is drug use and is, therefore, a deviant act. But even among other drug users,

inhalant users stand out as deviant.

Drug use. Inhalant users seem to be more likely to be involved with other

drugs. Although some use inhalants exclusively or preferentially, the studies

that have looked at a range of drug use often find that inhalant users are

heavily involved with other drugs as well (Jacobs and Ghodse 1988; Mata and

Andrew 1988, Carlini-Cotrim and Carlini 1988a; Dinwiddie et al. 1987; De

Barona and Simpson 1984, Ellison 1964, Sokol and Robinson 1963). This

heavier involvement with drugs in general may help to explain some other

findings. Padilla et al. (1979), for example, found that the major predictor of

inhalant use among barrio youths was knowledge about drugs, including information about their dangers. While this finding seems paradoxical, it may

simply be a reflection of the inhalant users’ greater total involvement in the

drug scene, including involvement with other drugs.

Crime and delinquency. In most studies that look at deviant behavior, particularly in older youths, the inhalant users are not only more deviant than nondrug users, but are more deviant than users of other drugs. Bachrach and

Sandler (1985) reported on youths referred by the juvenile court for treatment of inhalant abuse. While this study did not have an adequate comparison group of other drug users, it is notable that out of 40 inhalant users, 39

had been previously arrested, with a high number of arrests for a variety of

crimes other than drug use. Among the inhalant users in a Texas youth program, chronic sniffers had been arrested an average of 9 times, 40 times more

often than nondrug users, and twice as often as occasional sniffers (Stybel et

al. 1976). In other studies: (1) of Mexican youths, two thirds of the inhalant

users who were patients in a treatment program had been arrested compared

63
with only 3 percent of a control group (Berriel-Gonzalez et al. 1978); (2)

among Mexican-American youths in Texas drug prevention programs, inhalant users were more likely to have been stopped and questioned by the police, to have been arrested, and to be on probation (De Barona and Simpson

1984); (3) among emergency room admissions, inhalant users were more

likely to have had trouble with the law than both non-drug users and polydrug

users who did not use inhalants (Korman et al. 1980); and (4) in a Seattle

study of predominantly middle class white-Americans, inhalant users had

more police problems and were more likely to be runaways (Crites and

Schuckit 1979).

Inhalant users are also likely to get into trouble with the law earlier than users

of other drugs. The Berlin opiate addicts who used inhalants had already had

three offenses by the time other opiate addicts were arrested for their first

offense (Altenkirch and Kindermann 1986). Among adolescent delinquents

in London, on the average, the first arrest of inhalant users occurred about a

year and a half before the first arrest of users of other drugs (Jacobs and

Ghodse 1988). Reed and May (1984) found that inhalant-using delinquents

from a city in the southwestern United States, when compared with other

delinquents, had been arrested almost three times as often, were arrested

more often for more serious crimes, and were younger at time of first arrest.

Psychological Characteristics

The picture thus far is that inhalant users are a group with serious social and

societal problems. Do these problems result in, or are they accompanied by,

high levels of psychopathology or other personal adjustment problems? The

research that looks at psychopathology and personal/emotional characteristics

is neither as extensive nor as consistent as that describing the social problems

of inhalant users.

Early studies suggested that inhalant users might suffer from great emotional

distress. Case studies, for example, indicated that inhalant users might be

anxious and depressed (Weise et al. 1973). Smart and his colleagues found

that inhalant users had higher scores on the Taylor Manifest Anxiety Scale,

had been treated more often for emotional problems, and that they were more

alienated (Fejer and Smart 1973; Smart et al. 1972).

A few recent studies have explored differences in emotional distress. Oetting

et al. (1988) found that young Native-American inhalant users showed more

64
emotional distress than young marijuana users or controls, including depression, anxiety, feeling blamed, and anger. Jacobs and Ghodse (1987, 1988)

found that more adolescent delinquents who used inhalants were depressed

than adolescent noninhalant users who used other drugs.

There is some evidence that inhalant users are lower in self-esteem. De

Barona and Simpson (1984) found lower self-esteem and satisfaction with social relationships. Annis et al. (1971) found inhalant users were lower in variables that would logically relate to self-esteem. A study of youths in Indian

boarding schools found that inhalant users had lower self-appraisals, although

the self-ideal difference was the same as that for other youths (Wingert and

Fifield 1985). It might, however, pay to look in more detail at these self-ideal

differences. In a study that did not examine drug use, Cole et al. (1967) found,

on average, no self-ideal differences between a seriously disturbed group of

adolescent girls and controls, but this statistical result occurred because the

disturbed girls either had very high discrepancies or very low (and unrealistic)

discrepancies; so the use of an average score covered up real and important

differences in self-ideal discrepancy. This may have occurred in Wingert and

Fifield’s study.

When the populations studied are from inpatient psychiatric units, it is not

surprising to find diagnosed psychopathology. For example, Dinwiddie et al.

(1987) found that more than half of a small number of chronic solvent abusers

met the criteria for antisocial personality disorder. Crites and Schuckit (1979)

also found that the most common diagnosis for inhalant users was antisocial

personality disorder. An exception was a Mexican study, where almost half of

the inhalant users had a diagnosis of depression, but nothing is known about

rates of diagnosed depression in other groups of Mexican drug users

(Guitierrez et al. 1978).

Almost half of a group of adolescent inhalant users who were hospitalized for

treatment in Texas were diagnosed as having adolescent adjustment reaction

(Comstock 1978). The MMPI suggested less pathology in the inhalant users

than in other drug users, but a more detailed examination of the findings suggest more pathology among inhalant users than the initial results suggested.

For example, the MMPI profiles for other drug users had peaks on scales 4

and 9, suggesting primarily hostility, rebellion, and acting out behaviors

somewhat typical of many adolescents. The profiles of the inhalant users, on

the other hand, involved scales 4, 6, and 8, suggesting the presence of more

65
thought disorders. Further, if the adolescent norms that take into account the

high levels of rebelliousness and acting out of adolescents had been used to

profile the MMPIs instead of the adult norms, the inhalant group may have

been judged to have more, instead of less, pathology. The inhalant users were

also the only group to show more indications of pathology after treatment, a

result the authors suggest may be due to uncovering of underlying pathology.

Inhalant users do seem to suffer from greater emotional distress, and some

inhalant users may indeed have serious personality disorders. The evidence

that inhalant abuse is caused by serious psychopathology, however, is not very

convincing, at least at this time. A reasonably long-standing pattern of drug

use, particularly when accompanied by other deviant behaviors—as it is in inhalant users—could, without any further information on psychological functioning, lead to a diagnosis of personality disorder or antisocial personality

disorder. An adolescent reaction to the family problems that are often associated with inhalant use (broken families, family hostilty, and aggression) could

easily lead to a diagnosis of adjustment disorder in an adolescent, another diagnosis that has been applied to inhalant users in some studies. Those diagnoses may accurately describe the behaviors, but a diagnosis of a personality

disorder or an adjustment disorder can carry the implicit message that the behavior is caused by or rooted in that psychopathology. That conclusion is not

really warranted, since the signs of emotional distress and the behaviors of inhalant users could equally be simply an outcome of the social and family

problems and social environment of the inhalant user, and not a result of personal psychopathology. This line of reasoning is expressed well by Gilbert

(1983), who argues that the “disordered existence” of inhalant users predates

their sniffing, as inferred from the enduring nature of predisposing social and

family problems more common to inhalant users.

Peer Drug Involvement

One stereotype of the heavy inhalant user is that of the social isolate or

“loner.” When people working with inhalant users get together, they often describe this kind of user, so they do exist. Research reports, however, are

highly consistent in describing most inhalant use as a group activity. In an

early report on inhalant-using youths in Texas, Stybel et al. (1976) stated that

about three fourths of inhalant use occurred with other youths. Among

London delinquents, 75 percent of users inhaled with friends (Jacobs and

Ghodse 1988). Among adolescent users in Northern Ireland, nearly 80 per66
cent inhaled with friends (Lockhart and Lennox 1983). More than 80 percent

of Brazilian “street kids” used with their friends (Carlini-Cotrim and Carlini

1988b). Among Native American children in a boarding school, sniffing was

typically done in a group (Schottstaedt and Bjork 1977). Among poor

Mexican youths, 90 percent used with their friends.

The kinds of friends that inhalant users have may be an important factor in

their inhalant use. Inhalant users may have a narrower group of friends, with

higher deviance among those friends. In one study, for instance, the friends of

inhalant users all lived within their impoverished neighborhood, while many

of the control group subjects had friends outside of the neighborhood

(Berriel-Gonzalez et al. 1978). While family sanctions against inhalant use

tend to be high, even in the families of inhalant-using youths (Bachrach and

Sandler 1985; Beauvais et al. 1985; De Barona and Simpson 1984), sanctions

against inhalant use by peers are much lower (Bachrach and Sandler 1985;

Beauvais et al. 1985). Chronic inhalant users in Texas spent more time with

their friends, and their friends were more deviant (De Barona and Simpson

1984). Friends of inhalant users may use more drugs (Mata and Andrew

1988), and the friends of inhalant users are also likely to be using inhalants

(Bachrach and Sandler 1985; Oetting et al. 1988; Stephens et al. 1978).

In general, more than three fourths of inhalant use is probably with friends.

This leaves a considerable gap, however, showing that a significant amount of

inhalant use does occur when the user is alone. From general experience of

those working with inhalant users, solitary users seem likely to be more disturbed and have more problems. Only one study compared those who use

alone with those who do not. The authors felt there was more psychopathology in those who used alone (Guitierrez et al. 1978). Consistent with this

general observation were findings from a recent case study (Mathew et al.

1989) of a young, heavy inhalant user who sniffed alone. This individual’s extreme behavioral disturbances, especially aggressiveness, resulted in rejection

by her peers and, eventually, social isolation.

Culture

The location of “hot spots” of inhalant abuse in Hispanic barrios and on

Indian reservations suggests the possibility of cultural influences. Studies that

point to differences in drug use rate related to ethnicity usually assume that

the problems are occurring because youths are caught between two cultures

67
(Gilbert 1983; Guitierrez et al. 1978; Nurcombe et al. 1970). Gilbert (1983)

expresses this clearly, stating that the Hispanic inhalant users in her study

were “disengaged from the symbols and traditions of his/her culture or origin

and concomitantly rejected by the culture of the dominant majority” (p. 82).

There are, however, almost no actual studies of the cultural identification of

minority youths and how that relates to inhalant use. The exception is a study

of Native American “child polydrug” users (Oetting et al. 1980). The child

polydrug pattern occurs in children 14 and under and involves use of both inhalants and marijuana. The study noted that children who were highly identitied with Native American culture or who were bicultural were slightly less

likely to be child polydrug users. Studies of older Indian youths, however, did

not find this relationship between cultural identification and drug use, and in

another study, these authors indicated that the relationship between cultural

identification and drug use is not strong and is highly complex (Oetting and

Beauvais 1990).

There is another application of the term “culture” that may be highly related

to inhalant use—the fact that the most serious levels of inhalant use may occur in specific drug-oriented subcultures. The evidence that inhalant use is,

predominantly, a group activity is discussed above. Perhaps the most extreme

example of a subculture is reported in Leal et al.‘s (1978) study of “street kids”

in Mexico City, youths who have essentially severed all ties with their families

and formed their own subculture, probably to replace the family, a subculture

oriented around street survival and inhalant use.

Psychosocial Characteristics and Treatment Research

Experimental research aimed at altering psychosocial characteristics, either

through prevention or treatment, could add to knowledge of the underpinnings of inhalant use. No studies have been specifically designed to address

this kind of question, but some hints that are relevant to psychosocial characteristics are in the sparse literature on treatment. Barnes (1979) reviewed the

early treatment case studies and reported mixed results. He also reviewed the

one treatment study where various methods were tried (Rubin and Babbs

1970), noting that although solid data were not provided, a program that utilized intensive work with families, school, and the peer group may have had

some success. The results agree with other literature, suggesting the importance of social environment. Carlini-Cotrim and Carlini (1988b) reported

that some of the Brazilian street kids were able to get involved in a welfare in68
stitution. It provided leisure time activities, including creative crafts that they

could sell. The youths in this program reduced their drug use, particularly

those who stayed both day and night at the institution. The children who were

able to get involved were self-selected, so alternative explanations cannot be

ruled out, but the fact that a change in social environment was related to

change in inhalant use should probably not be ignored. These studies are

weak but consistent in suggesting that the social environment may be an important factor in the maintenance of inhalant use and that changing the social

environment may be useful in treatment.

In contrast, psychotherapeutic approaches have not been notably successful

(Comstock 1978; Guyer-Christie 1978), nor have traditional drug treatment

programs. In one study, all 10 patients provided with inpatient drug rehabilitation had relapsed within 6 months (Dinwiddie et al. 1987). The ability of

short-term treatment to alter relatively well-established psychological characteristics is questionable, but equally, social, rather than psychological, factors

may be causative for inhalant use and essential for treatment.

Summary

In several ways, the research on inhalant use is remarkable. First, early research, prior to 1975, and research completed since then are essentially consistent and lead to the same conclusions about inhalant users. Considering

that drug use has changed radically over this time span, differences in findings

over time might be expected. Instead, the recent research has only expanded

on and amplified the conclusions reached by Barnes in his 1979 review.

Second, the research is remarkably consistent; within a psychosocial area, the

studies show high agreement. Third, the research results lead to similar conclusions regardless of age of the study population—inhalant users are found

among the subjects who have the fewest social resources at any age and in any

group. Fourth, results are consistent across cultures. Research results from

four continents and, within the United States, from a number of different cultural contexts, are fundamentally in agreement.

The most general conclusion is that inhalant users are likely to be marginal in

society. Inhalant use is highest where poverty, prejudice, and lack of opportunity are endemic. Inhalant users are more likely to come from families that

are unstable and dysfunctional. Youths who are failing in school, showing

lack of ability to meet the requirements of that environment, are also among

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those most susceptible to inhalant use. Inhalant users have friends who are

also marginal; they are likely to be involved with drugs and are probably also

using inhalants, since most inhalant use is a group activity. Those who do

move on to solitary use, however, are probably the ones with the most problems. With all these social problems, it is not surprising to find that inhalant

users are also likely to have problems with school authorities and to be involved in criminal behaviors. In addition, inhalant users may suffer from

great emotional distress.

A Model For Psychosocial Research

on Substance Use

A generalized model for psychosocial research can be visualized (figure 1).

The columns list psychosocial characteristics—cultural, social, and

psychological.

Culture provides a foundation of language, beliefs, values, and culturally approved or sanctioned behaviors. Social forces that affect the person include

the community, the socioeconomic opportunity structure, school, work, religion, family, and peers. Psychological characteristics, traits, attitudes, and cognitions interact with these social characteristics to alter the probabilities of

different behaviors.

The rows in figure 1 cover the types of psychosocial research and suggest a

temporal order in a research agenda from naturalistic observation through

experimental research. The general trend of research should follow this path,

but the model is not meant to specify a rigid research agenda. The ultimate

outcomes that derive from research are too unpredictable to warrant an inflexible policy. The model does suggest that, at certain stages in an overall research plan, particular types of studies may be more profitable than others.

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Figure 1. A generalized agenda for psychosocial research

Naturalistic Observation

Basic Epidemiology

Ethnographic Studies

Cross-sectional Studies

Longitudinal Studies

Experimental Research:

Analogue Studies

Prevention

Treatment

Psychosocial Characteristics

Cultural Social Psychological
It also suggests that the value of the research at later stages may depend on

progress made in different types of research at the earlier stages. The risks to

subjects also increase through the stages in this research agenda. For example,

cross-sectional research can be anonymous while longitudinal research cannot

and therefore adds risk. Prevention or treatment involves manipulation of

subjects, adding additional risk. With increasing risk there is increasing need

to make sure that research results are likely to warrant that risk, and that need

is usually met by research at an earlier stage in the agenda.

An overall planned research agenda should consider the state of scientific

knowledge at any point in time, should determine what has been achieved at

each of these stages, and then focus current efforts on filling in gaps and

moving effectively to the next stage of development of knowledge. Research

designs that fit into this overall plan at any stage of its evolution should,

therefore, be sought out and given strong consideration, while proposals for

other kinds of research should be questioned but not automatically rejected.

As the knowledge base builds from successful efforts at earlier stages, new

kinds of research become cost-effective, and the research agenda shifts and

expands, moving on to the next stages.

To illustrate this point, when this chapter was first drafted, “ice,” or smokable

methamphetamine, had received considerable publicity predicting that it

would be the next major drug problem. An expensive prevention research

study could have been proposed at that time aimed at reducing use of ice. The

model for forming a research agenda, however, would suggest caution. If prevention is undertaken before solid progress has been made in epidemiology, it

could be aimed at inappropriate groups, populations, or ages. If reliable and

valid measures of “ice” involvement and of intervening or process measures

were not developed and tested, an expensive prevention study might be

wasted because the measures it used were unstable or invalid. If data on psychosocial correlates of ice use were not available, a treatment program could

easily be aimed at altering variables that would have no relevance to use of

ice. In fact, the caution would have been well rewarded; the expected “ice age”

never did appear on a widespread basis, and a major prevention research program would have been wasted.

The following sections take each row of the model in figure 1 in turn. They

briefly discuss the nature and limitations of that type of research and how it

fits into an overall psychosocial research agenda.

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Types of Psychosocial Research

Naturalistic Observation

One stage must precede any other research—a problem has to be “noticed”

before it can be studied. This naturalistic observation stage usually cannot be

planned; it can only be identified after it has occurred. For example, Brecher

(1972, p. 321) pointed out that, while it is likely that people sniffed glue, this

practice is not mentioned in print prior to 1959. Until glue sniffing was noticed, further research could not take place. Once a problem is identified, the

next studies may also fall into the general category of naturalistic observation.

They may be case studies or studies that look at the behavior in small, not very

generalizable, subsegments of the population. Many “one school” surveys are

of this type.

From the point of view of psychosocial research, a major purpose of naturalistic observation is to identify a problem and feed that information into more

formal epidemiology studies, suggesting what to assess, how to measure it,

and what sampling frames may be important. This “we have a problem” function is not, however, the only use of naturalistic observation. It can be a powerful tool in the hands of the competent scientist, when observation leads to

theory which is then tested through further observation to alter the theory.

The most serious limitation of the method is the possibility of bias—of seeing

only those facts that confirm the emerging theory. The accompanying advantage is that the door is always open for invention, discovery, and innovation.

Naturalistic observation does not end when other types of research start. New

phenomena always need to be identified, and they point the way to further research needs. One example is a newly observed pattern in adult inhalant use.

Inhalant-dependent adults are usually socially isolated and alienated, the use

of inhalants may be obsessive and continuous, and unlike most use by younger

users, inhalants are not usually used as a “social” drug. In one location, however, a group of adult inhalant users are getting together in groups, renting a

motel room, and buying a case of spray paint for a weekend binge. This naturalistic observation clearly sets the stage for further research on a hitherto

unusual pattern of use.

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Basic Epidemiology

Once a problem has been noticed, epidemiological research needs to establish

the characteristics of the problem, identifying its nature, extent, distribution,

and how it relates to population demographics. Epidemiology may also provide an essential fuel for the research endeavor. If everyone knows that there

is a problem, there may be no difficulty in obtaining political and policy support for work on that problem. But if a problem is obscure, if there are

groups that would argue that there is no real problem, then solid data on epidemiology are needed to obtain support and funding for research.

Epidemiology forms a foundation for further research. It indicates what

groups need to be included in future studies. The base rate of a behavior determines how many subjects may need to be included to obtain adequate data

to determine the correlates of a behavior. Identification of at-risk groups or

locations determines where ethnographic research should be done.

Epidemiology studies are actually often combined with cross-sectional research on psychosocial correlates of use, a good illustration of the blurring

across categories that is inherent in presenting a model that defines separate

categories.

Use of drugs changes over time, and unless those changes are known, psychosocial research results may be confusing. Cross-sectional studies of correlates of use, for example, completed a decade apart, could easily show different relationships between inhalant use and psychosocial characteristics.

Witness marijuana. In 1970, when its use was still relatively infrequent among

younger adolescents, only the more deviant youths would be likely to have

used it. In 1980, when adolescent drug use was at its highest level, many

youths who were not particularly deviant would have used marijuana.

Without solid data on trends in drug use, studies done at different times may

appear to be in conflict, when in fact there is an underlying consistency.

Ethnographic Studies

Ethnographic studies, by their nature, can only obtain data from a limited

number of subjects and may be at their best when they examine one specific

and narrow subgroup. Until the distribution of the problem is known from

epidemiological research, it is difficult to decide where an investment in these

studies will be most valuable. There may be cogent theoretical reasons for

studying a particular group that have little to do with the overall distribution

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of the problem, and if so, those reasons provide sufficient justification for a

personal research commitment. A research policy, however, may have to be

more stringent, and those funding ethnographic research may need to be concerned with efficiency; in order to be funded, the results may have to be obviously generalizable to an “important” group, a group where the problem

seems to be concentrated or where the consequences are most serious.

Ethnographic research provides a rich source of information about detailed

behaviors, social and cultural contexts, meanings, attitudes, values, and beliefs. Certain kinds of questions can only be addressed by this type of study.

In addition, other types of research may benefit from the rich detail and examples provided by ethnography. The value of research on correlates of use,

for example, depends on the inclusion of measures of variables that are relevant to the problem, and without input from ethnographic studies, crucial

variables may not be included. As an example from our own research, in the

early stages of an ethnographic study of drug using adolescents, we found that

a major component of their beliefs and attitudes centered around distrust.

Although they tended to see anyone who used drugs as a friend, they had also

been ripped off by these friends, who stole money, drugs, and property. Based

on these interviews, measures to assess trust/mistrust are now being constructed for inclusion in our cross-sectional and longitudinal surveys.

One major limitation of ethnographic studies is the cost per subject in research time. Observations and interviewing take time, and the number of

subjects must, therefore, be low. Observations are also usually restricted to

one or two locations. To what extent will the results generalize to other

groups? Another limitation is analysis. It is hard to describe and defend the

analysis of the data, since the conclusions usually grow out of and gradually

emerge from insight into the observations. The inability to describe analyses

and predict results can prove to be a critical factor that prevents reviewers

from being sure that a study warrants funding.

This early input into the research agenda is only one potential benefit from

ethnographic studies. The ethnographer can sometimes provide information

on subgroups that cannot otherwise be studied. An example is Terry

William’s ongoing study of crack houses, whose residents probably could not

be reached in any other way (unpublished study). The ethnographer can also

provide insights into complex interactions and cultural roots and can discover

linkages between behaviors and contexts that could not be teased out of other

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forms of data. The theoretical constructs that emerge from the best ethnographers are accompanied by rich descriptive detail that is a convincing image

of real people in a real world—a balance for cold and formal drug statistics

and abstract or arcane theories.

Cross-Sectional Research

Cross-sectional studies come in a variety of forms. Some are products that

emerge from inclusion of psychosocial measures on instruments used to assess

national epidemiology. Johnston, O’Malley, and Bachman’s studies of drug

use of high school seniors provide an important example (1989). Others are

done in one location, such as Jessor and colleagues’ valuable triethnic study

(1968). Cross-sectional studies can have different purposes, such as research

designed to examine factor or cluster structures, retrospective studies to find

preliminary evidence of precursors of drug use, or path analyses that explore

the intercorrelations of variables. Studies can be limited to one population or

can compare groups, for instance by age, ethnicity and gender. The value of

these studies is that they can provide useful information on how groups differ

from each other—in this case, how inhalant users differ from other drug users

and from those who do not use drugs. They can identity potentially salient

characteristics, provide fundamental information on reliability and validity of

measures of dependent and independent variables, and can lead to theories

and hypotheses that guide further research. The studies do not have to be exploratory; cross-sectional studies can also provide confirmatory evidence for

construct validity where a theory predicts that certain specific relationships

should exist.

Their major limitation is that cross-sectional studies cannot yield direct evidence of temporal relationships. A psychosocial difference between inhalant

users and nonusers could identify a trait that was a precursor of use, that was a

result of use, or that might be a correlate of a factor that related to both that

trait and inhalant use. There might be strong theoretical reasons to believe

that a relationship does reflect a precursor of use or that it developed after

use began; but until longitudinal or experimental studies are done, it is important to remain skeptical.

The major advantages of cross-sectional research are cost, flexibility, and immediacy. Large arrays of data can be obtained rapidly and analyzed immediately. Longitudinal, prevention, or treatment research are likely to be expen76
sive and to require extended time to get results and should usually be undertaken only after a proper foundation has been laid using cross-sectional

studies.

Longitudinal Research

Longitudinal research adds a very important element. It provides direct data

on temporal relationships that cross-sectional studies cannot. This additional

information adds greatly to understanding how psychosocial characteristics

relate to behavior. Longitudinal studies are usually aimed at one of two

goals—determining the consequences of a behavior or identifying the precursors of a behavior. In some ways, a study of consequences appears to be easier; a group engaging in the behavior can be identified, a reasonably wellmatched comparison group can be obtained, and after a period of time, the

groups can be compared. The difficulty and the cost come in trying to track

people over time. Inhalant users may present a particular problem in this regard, since they may be quite deviant and are likely to drop out of school, to

be unemployed, and to move frequently.

Identifying precursors of a behavior with a relatively low base rate, such as inhalant dependence, can be difficult and costly. It requires assessing the psychosocial characteristics of large numbers of youths to be sure that, down the

road, enough inhalant-using subjects are available for analyses. The problem

is exacerbated because those few who do become inhalant dependent may not

be found on followup.

Despite their problems, longitudinal studies are of great importance.

Through longitudinal studies, it should be possible to determine whether a

particular psychosocial characteristic appears before the behavior, along with

it, or develops subsequent to the behavior. It is tempting to interpret these

sequential relationships as causative, and in general, a temporal relationship

is important evidence for causation. There are, however, other plausible alternative hypotheses that need to be considered. For example, the characteristic that appears earlier and the behavior that appears later may both be

caused by some other underlying factor. The sequencing may occur for other

reasons. For example, those who use cocaine almost always used marijuana

first. Does marijuana use, therefore, cause cocaine use? Not necessarily.

Youths with a relatively high general penchant for or attraction to drug use

may end up using both drugs. They may have started with marijuana only be77
cause it is more available, because it is believed to be less harmful, or even

because it costs less.

A historical trend could also account for results. Attitudes, beliefs, or drug

use can change in society in general, and earlier and later results may derive

from those changes. For example, a study tracking drug use in a group who

were 10 years old in 1970 might find increases with age until they were 21 in

1981 and then decreases in drug use after that. But general drug use for the

whole population shows exactly the same trends over these years, increasing

until 1981 and then declining. How much of the result is age/drug related and

how much is due to general social trends? Studying several age panels would

answer the question, but as new panels are added, costs can soar.

Another critical problem with longitudinal studies is attrition; as many as half

of the subjects may disappear over time. Would the results be different if all

the subjects could have been found? When attrition is high, pretest results for

those found and those not found are almost bound to be the same, since a

small group of “different” subjects in either group would not have much effect

on the mean scores of the large number of subjects in that group.

Nonsignificant statistical pretest differences may not mean the groups are

really equivalent.

Despite these problems, longitudinal studies are of great value. They do elucidate temporal relationships that are critical to understanding how psychosocial characteristics lead to and are influenced by drug use. The results must

simply be treated with the same caution that is appropriate to all research results, with careful consideration of possible alternative explanations.

Experimental Research

All of the methods described to this point involve observing and assessing existing characteristics and behaviors and examining existing relationships.

Experimental research involves altering or manipulating variables and determining the outcome. Three general types of psychosocial research involve

changing or manipulating variables and, therefore, fall into the category of

experimental research: (1) laboratory analog studies, (2) prevention research,

and (3) treatment research.

A major advantage of experimental research is that it adds one more link to

the chain of evidence needed to establish causation. A good experimental

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design can eliminate many of the most common alternative explanations.

Unfortunately, from the point of view of pure research, experimental psychosocial research must be done with humans, and because of ethical and

practical considerations, must often use designs that are not optimal for

eliminating alternative explanations.

Laboratory analog studies have the advantages of being relatively inexpensive

and offering immediate results. They usually provide the most control over

experimental conditions and utilize the best experimental designs, but sometimes because of this careful control, results may have minimal application

outside the conditions of the laboratory. Prevention and treatment research

programs are the most realistic; they deal with real people in real environments. They are, in one sense, “causal” research, since variables are manipulated, and outcomes of changing the independent variable can be assessed.

They are, however, much less amenable to well-controlled experimental design. Their costs are so high that it is usually impossible to include all of the

conditions that a good experimental design would suggest are needed, and

they usually have little control over extraneous variables in the lives of participants that could influence results. If they fail, there are usually too many

possible reasons for failure to allow isolating the causes. Findings can also be

delayed, particularly if expected effects are long term.

Experimental studies in general are placed at the final stage in the research

agenda, suggesting they should be strongly based on prior research. Actually,

some types of analog studies probably do not have to await progress from

other methods of research. They may be more applicable to the problem once

there is considerable information about it, but at any time they might add

small pieces to the equation that helps us understand behavior. The ethics of

manipulating subjects are not likely to be a major issue, since studies almost

always use fully informed volunteers and the procedures are unlikely to endanger subjects. More experimental studies of this kind should be done.

Prevention programs, on the other hand, need to be based on solid research

to ensure that they are targeted appropriately and aimed at characteristics

that may influence the outcome. Without a solid prior research base, prevention programs have to be based on beliefs about what ought to work, or on

programs that worked for some other problem. The failure of so many prevention programs that used drug education may be a good example of the

former; they ought to have worked, they just did not.

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An example of trying to transfer a program from one area to another is the

considerable research on prevention of smoking. One finding is that youths

will, at least temporarily, reduce smoking when they believe that it leads to

negative social consequences. But would this kind of program work for inhalant users, some of whom may be youths who see rejection by “good kids” as

an asset, not a liability? Similarly, treatment programs that are not derived

from research must be based only on prior treatment experiences with other

problems, and generalizing from that experience may be unwise. If inhalant

dependent adults, for example, have different psychosocial characteristics

from alcoholics, why should a treatment based on Alcoholics Anonymous

work for them?

Initiating prevention or treatment without a firm, data-grounded theory that

suggests why it may work is questionable. There is always the excuse that

something has to be done about the problem, but it must be remembered that

prevention and treatment involve manipulation of people, and this manipulation can result in harm. The harm may even come simply from failing to be

successful; what damage is done when prevention or treatment fails? Does it

make people feel like failures? Does it lessen the chance that future interventions will succeed? Trying to change people without relatively strong evidence suggesting that they will be helped is probably not justifiable.

An Agenda for Psychosocial Research

on Inhalant Use

Checking the published research against the model for a research agenda presented in figure 1 shows considerable effort related to early parts of the

agenda: naturalistic observation, epidemiology, and cross-sectional research.

The noticing aspect of naturalistic observation occurred some time ago and

was followed by a number of small studies that would fall in the same category. There is, however, no report of an in-depth set of naturalistic observations that involves strong theory development or hypothesis checking. In contrast, there is considerable knowledge of inhalant epidemiology, although, as

Beauvais points out (this volume), gaps still need to be filled. Nearly all of the

papers that deal with psychosocial characteristics present results from crosssectional research. A few studies have an ethnographic flavor, but none are

true ethnographic studies, and there are some minimal reports on treatment.

No longitudinal, prevention, or laboratory analog studies were found.

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A model research agenda on inhalant use is proposed. In figure 2 the rows

indicate the different types of research discussed in the introductory section of

this chapter. The columns list the three types of inhalant users (Beauvais and

Oetting 1987), showing that a research agenda needs to cover three groups:

young inhalant users, adolescent polydrug users who take inhalants, and inhalant-dependent adults. A third dimension lists the major transitions in

drug involvement, showing that different psychosocial factors could be involved in initiation, maintenance, dependence, quitting, and relapse.

Another dimension could be added, showing that psychosocial research

should explore cultural, social, and psychological characteristics. The most

consistent findings in the literature indicate that inhalant use is strongly related to being socially marginal. The emphasis in this proposed research

agenda, therefore, is placed on the social dimension. The finding that inhalant users are socially marginal across widely divergent cultures suggests

that, despite finding high rates of use in some minority populations, no specific cultural content is a major factor in use. Future research on culture

should, therefore, probably focus on marginality or lack of cultural stake

rather than on cultural content. More research is probably also needed on

psychological characteristics. Inhalant users may be more likely to suffer emotional distress, but that may be a result of their social problems rather than a

proximal cause of inhalant use. While cultural and psychological characteristics should not be ignored in a research agenda, social characteristics are the

most important definers of inhalant use and should probably be given more

immediate priority.

If the additional dimensions involving cultural, social, and psychological characteristics were added, figure 2 would have 315 cells, each defining a different

research project. Describing all of the possible research programs would be a

formidable prospect. Fortunately, major studies cut out larger blocks of figure 2 that cover a number of adjacent cells, and based on what is known about

inhalant use, some research projects emerge that should have high priority.

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Figure 2. Model for an agenda for pshycosocial research on inhalent use
The first two rows of the figure are not dealt with in further detail here. The

noticing aspect of naturalistic observation has already been accomplished,

leading to a considerable body of research on epidemiology and correlates of

use. As long as observers continue to witness new phenomena (and barring

emergence of a new Darwin), no specific research agenda in this area is

needed. The next row, basic epidemiology, has already been covered by

Beauvais (this volume). Suggestions for a research agenda, therefore, begin

with the next row in the diagram, ethnographic studies.

Ethnographic Studies

A number of possibilities exist for ethnographic studies, but the highest priorities should probably be given to studies of inhalant-dependent adults and

polydrug users who use inhalants. The primary focus of these studies should

probably be on the psychosocial factors involved in maintenance of inhalant

use.

Inhalant-dependent adults. There are strong reasons to believe that inhalantdependent adults are likely to be among the most disadvantaged and marginal

people in society. They probably cannot be examined except through ethnographic studies. They are not likely to show up in surveys, and even if

reached, many of them may not be able to accurately complete questionnaires.

The studies should cover urban nonminorities, Hispanic barrio minorities,

and Native Americans on reservations. Studies of inhalant dependent adults

in black ghettos should also be done; although inhalant use is lower among

blacks, some are inhalant dependent.

The questions that need to be answered center around the way that inhalantdependent adults exist within the broader social structure, how they fit into

the culture and the social environment. What are their patterns of substance

use? Have they moved to essentially solitary use or are they still part of drugusing social networks? What are those networks like, and how do they support inhalant use? What were the transitions in use, and when did they occur? What are their beliefs, attitudes, and preferences in relation to drug use?

Who are they? How do they survive? What social/personal interactions mark

their days? How are they viewed by others in their environments? Does this

vary by ethnicity/culture? What are the cultural roots of current attitudes of

others in their environment to these inhalant-dependent adults? Most cultures have social roles for misfits. Do inhalant users now occupy these

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niches? Are they scapegoats, the butt of jokes? Are they tolerated in certain

locations and when engaged in certain activities and not tolerated in others?

Adolescent polydrug users who use inhalants. Polydrug users are more likely to

use drugs within group contexts, and even their use when alone may be dictated by attitudes and beliefs formed in the group. Ethnographic studies of

these youths will probably need to involve both interviews and observations

of group behaviors and group dynamics. The same questions asked about inhalant-dependent adults would apply to these studies. Added would be questions about social structure and subculture of the groups. For example,

heroin users in barrio gangs can form small subgroups within a larger gang of

non-heroin users; is this true of inhalant users? Does group makeup and extent of solitary use differ on Indian reservations where travel is difficult?

What role does criminal activity play for the individuals and the group? The

probable high level of criminality in these youths suggests that the ethnographer will have to have unusual qualifications both to develop trust and to survive in a high-risk environment.

Cross-Sectional Studies

While nearly all of the existing published research is cross-sectional, there are

still numerous opportunities for important additional studies. Young inhalant users appear more frequently among those who are failing in school,

and polydrug users who use inhalants are also likely to have school problems.

More information is needed about the details of that poor school adjustment.

It might be assumed, for example, that youths who are doing badly in school

also dislike school, but only one study actually examined liking for school, and

it found no significant differences (De Barona and Simpson 1984). Since inhalant users may have high dropout rates, studies of the psychosocial characteristics that relate to inhalant use among school dropouts are also needed,

particularly Hispanic and Native American dropouts, the ethnic groups where

inhalant use is particularly prevalent.

Poor family adjustment is also a predictor of inhalant use, and there are indications that family problems when the child is younger may be particularly

damaging. Studies comparing parenting styles, discipline, and role modeling

as they relate to psychosocial characteristics and inhalant use of children

might contribute valuable information. The high rate of broken families

among inhalant users, and the importance of the extended family in the two

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ethnic groups at highest risk for inhalant use, suggest studies of the potentially protective effects of roles played by the extended family.

Deviance is a major correlate of inhalant use, but more detailed information

is needed. Among inhalant users, what kind of rebellious, hostile, or delinquent acts appear at what ages? How do tolerance of deviance and deviant

behaviors interact? What patterns of deviance are engaged in by the peers of

inhalant users? How do peer and individual attitudes and beliefs about deviance relate, and how are they related to beliefs and attitudes about inhalant

use, particularly among polydrug users who use inhalants?

Other research findings suggest areas in which no research has been done that

should be explored. The most important of these may be the role played by

violence in the lives of inhalant users. Chavez et al. (1989) found surprisingly

high levels of violence in the lives of dropouts, and this is worth exploring in

inhalant users. There is evidence of family fights and family arguments, but to

what extent are physical or sexual abuse factors that may underlie the general

marginality that precipitates inhalant use? Have inhalant users been beaten,

cut, shot, or raped? Violence could easily help create the marginal person

who is most susceptible to inhalant dependence.

Another area of importance may be cultural identification. Oetting and

Beauvais (1990) indicated that high cultural identification depends on having

a stake in that culture, on the person’s ability to obtain rewards and reinforcement from the culture. For youths, this stake is inextricably connected to

the family’s success in a culture. Identification with either minority or majority culture may be a protective factor, but the marginal families of inhalant

users may not be able to provide the foundation for a strong identification

with any culture. Oetting and Beauvais found that cultural identification is

not highly correlated with drug use in general, in either Hispanic or Native

American youths. There is, however, a high relationship between family

marginality and both cultural identification and inhalant use, and poor cultural identification could be a major factor in inhalant use.

Longitudinal Studies

The research agenda for longitudinal research has to start with some negative

considerations. Inhalant dependence is a relatively low base-rate behavior.

Some research projects that would otherwise be of great interest, therefore,

may become either too expensive or too impractical to make them worth at85
tempting. For example, initiation and maintenance of use by young inhalant

users may have its roots in early family disturbance. A longitudinal study

should obtain baseline data on family characteristics, parenting, child/adult

interactions, the extended family, family involvement, success in the minority

and majority culture, and handling of family crises. Of particular interest

would be the interaction of family characteristics and developmental stages,

since failure to complete very early developmental tasks may create the social

marginality that marks the inhalant user.

A very large baseline sample would be needed to ensure having an adequate

number of young inhalant users at followup to have sufficient power to assess

the importance of and the interactions between the large number of variables

involved. A study to determine the early markers of adolescent polydrug use

with inhalant use would be valuable, but the base rate of this behavior is even

lower. The length of these studies, and therefore their expense, would be even

greater. If there were high rates of attrition, the original samples would have

to be even larger. Convincing a funding source to support study of a sample

large enough to look at low base rate behaviors can be difficult. The answer

might be a national, multiagency, multidisciplinary, multicultural, longitudinal study of family characteristics and child development. Negotiating to

make sure that the study included adequate assessment of drug involvement

might be a problem. Multiagency studies in the past have often included only

superficial measures of substance use.

There might be greater potential in structuring longitudinal studies of highrisk groups. For example, a list of family risk factors would include (1) broken family, (2) a history of family conflict, (3) criminal arrest of family member, (4) no member of immediate family with more than 5 years of continuous

employment, and (5) a history of alcohol or drug abuse. A longitudinal study

could include a high-risk group selected to have three or more of these family

risk factors and, for comparison, a group matched only for ethnicity and

neighborhood. The rate of inhalant use in the high-risk group could be high

enough to allow the study to be completed at reasonable cost. A study following youths showing poor school performance, particularly those with

records of disciplinary actions or arrest, might include significant numbers of

youths who end up as polydrug users with inhalant use. These studies would

also be expensive, because identifying, locating, testing, tracking, and continuing to get followup data on these youths, who are likely to become dropouts

and who are on the fringes of society, would take large amounts of staff time.

86
A longitudinal study that determines the precursors of inhalant dependence

in adults is probably not feasible. The base rate is simply too low.

Followup studies of users, to determine how psychosocial characteristics are

related to consequences of inhalant use, should have a high priority and

should be done for all three types of users. The results could lead to important information about psychosocial correlates of maintenance, quitting, and

relapse. These studies would not suffer from base-rate problems. They are

costly, but only because following marginal people over time is difficult.

Inhalant users may be hard to find locally, but may not have the resources to

move. Unless attrition is inordinately high, adequate power can be obtained

with reasonable sample sizes.

A critical factor in any agenda for longitudinal research is making sure that

the baseline data include reliable and valid measures of all critical variables.

If variables have poor reliability or validity, the measurement models will not

stand up, and if a key variable is missing, the final results can lead to conclusions that are inaccurate or misleading. Cross-sectional research is economical enough so that risks can be taken, since they can be expected to be selfcorrecting over a number of studies. Longitudinal studies are expensive and

cannot be given the same latitude to err.

Laboratory Analog Studies

A useful set of studies that could lead to valuable information about inhalant

users would involve determining how inhalant users differ from other youths,

both users of other drugs and nondrug users, in their response to controlled,

laboratory-imposed conditions. Studies can be aimed at any of the three types

of inhalant users. The independent variables can range from highly theoretical to potentially practical. For example, these users are likely to be marginal

in society. Do they, therefore, have inappropriate proxemic responses? Do

they provide social nonverbal cues to others that lead to rejection or dislike?

Response to standardized laboratory conditions can provide answers to these

and other questions.

Many inhalant users have a history of family and authority conflicts. Do certain experimental conditions, therefore, such as presentations of family pictures or taped stories about family conflicts, lead to differing psychophysiological or behavioral responses? Do parents of inhalant users show different

responses to standardized presentations of family crises?

87
Inhalant users consistently show high rates of school problems. Are there

differences between inhalant users and other youths in learning style? Do

they perceive problems in different ways? Do users show evidence of perceptual or learning disabilities? Do these change or disappear with time since

the last episode of use? Do they respond accurately to some types of presentations of information and not to others? Do they differ from other youths in

response to learning tasks or social/psychological situations? Do young inhalant users perceive and respond differently to messages about drug use? Is

drug use grouped by gender, by age, by ethnicity interactions with the source

of the message, the content, the style, the intensity, and so forth?

Obviously, a very wide range of laboratory studies might shed some light on

the psychosocial characteristics of inhalant users and how they differ from

other youths. If a researcher had access to inhalant users, most of these studies would be very economical. Only a few would even need external funding.

The opportunity for an innovative and creative researcher with limited resources to make a contribution in this area of research is great.

Prevention

Simpson, and Jumper-Thurman and Beauvais (this volume) review the prevention and treatment research in detail and suggest a research agenda. Here

we are concerned only with prevention and treatment as a form of experimental research that may shed some light on psychosocial links to inhalant use.

The goal of a psychosocial prevention study would be to alter one or more

psychosocial characteristics that are theoretically causes of inhalant use. The

effect on inhalant use would then be determined.

The major psychosocial variables that the literature suggests are potential

causative agents are family conflict and poor school adjustment. Prevention

programs to alter these characteristics should probably be tried, because even

if inhalant use did not change, the potential benefits might be great. But supporting a prevention study of this kind is a problem. Demonstrating success

in preventing a low base-rate behavior would require large numbers of subjects, even more than a longitudinal study, since a control group is needed.

More subjects must be added, because a prevention program, no matter how

effective, cannot change everyone who is treated, and of those whose psychosocial characteristics are changed, only a portion will reduce inhalant use.

As with longitudinal research, identifying and treating a high-risk group with

88
a high potential base rate of future inhalant use can improve the efficiency of

the study, and psychosocial prevention research will probably have to take this

form.

A second solution might be to increase subject numbers by developing methods for systemwide prevention, for example, using media to change psychosocial characteristics for whole schools or whole communities. This method

would probably only work for prevention aimed at young inhalant users. The

two other types of users would probably not be in the school system to be

tested at followup.

Treatment

As a psychosocial experiment, treatment would look at the effects on the dependent variable, inhalant use, of altering psychosocial characteristics that either (1) maintain inhalant use, (2) enhance potential for quitting, or (3) prevent relapse. In establishing an agenda for psychosocial treatment research, a

key question is what psychosocial characteristics should become the independent variables.

The research shows that inhalant use is related to peer drug involvement, and

peers are likely to be a major factor in maintenance. Altering these peer relationships may be critical for quitting and prevention of relapse (Oetting and

Beauvais 1987). Experimental approaches to change these relationships, either by separating the subject from the group or changing the group’s behavior, probably should be tried, particularly for young inhalant users and adolescent polydrug and inhalant users.

Early and persistent family problems may be among the initial causes of susceptibility to inhalant use and may also be a factor in maintenance. Except

when family breakdown is extreme, the young inhalant user is often still in

touch with the family. Given the nature of the families of inhalant users, a

highly structured form of family therapy and continued monitoring of the

family to prevent abuse and deal with crises might alter the independent variable enough to see a result. A program like Vega’s (1990) Projecto Bienstar,

which used servidora to provide Hispanic women with cognitive-behavioral instruction on coping with family conflict, might be tried. It may be too late for

family treatment to be useful for adolescent or adult users.

89
The underlying theme of psychosocial research on inhalant users is marginality. They are almost invariably found to be poorly adjusted to and incapable

of functioning effectively in society. If an individual does not have the capacity to succeed in society, unless something can be done to alter that basic

characteristic, treatment of inhalant users may prove to be futile. Even if they

stop using, what does life have to offer? Without the capacity to adapt to and

succeed in the world, they would be likely to return to inhalant use. For example, young inhalant users have problems in meeting the requirements of

school. Even if they stop using inhalants, if they cannot succeed in school,

they will drop out and continue to be marginal in society. In that case, the

probability of relapse to inhalant use seems high. Experiments designed to alter their school adjustment should be attempted. Adolescent polydrug users

who use inhalants may have similar problems, but as they get older and work

becomes more relevant than school, alternative treatment possibilities may

need to be explored such as job training or placement. Inhalant-dependent

adults, from all reports, are likely to be unemployed and unemployable.

Building their ability to function successfully in the work environment may

also be essential if relapse is to be prevented. A treatment program to change

work adjustment should take into account the fact that these inhalant users

are likely to be very low on the work adjustment hierarchy (Oetting and

Miller, 1977). Placing them on a job will not be enough. They may need help

with many of the stages essential to developing work adjustment.

Summary: A Psychosocial Agenda

The descriptions of research show that every type of research can offer valuable potential insights into the psychosocial underpinnings of inhalant use.

No one kind of research is preferable; each type of research answers different

questions in different ways. Every type of research offers certain assets and

has specific limitations. An overall research agenda should support a variety

of studies, chosen to answer questions that are important given the current

state of the art.

Tough minded cost/benefit decisions may need to be made. A difficult

dilemma occurs because, even if a treatment program for inhalant-dependent

adults were maximally successful, they tend to be so disadvantaged that it

would likely lead only to entry level employment for a few of these people at a

relatively low wage. Given their current status, this might be a major and

beneficial outcome for them, but the result does not seem to be a major ben90
efit for society. Would the same funds lead to more societal benefits if they

were devoted to an intensive research study to determine how altering school

abilities of high-risk children changes their propensity for inhalant use?

Fortunately, since it will probably always be a costly endeavor, an investment

in psychosocial research on inhalant use has benefits far beyond the immediate ones. The characteristics that we are learning about are important aspects

of personal/social adjustment in general. Inhalant users are an extreme

group, but because they are extreme, results may stand out more clearly.

What we learn may help those who are tragically involved with inhalants. But

more important, what we learn may be fundamental lessons about how cultural, social, and personal characteristics interact, either to develop resilience

and enhance human potential or to create susceptibility to problems and

destroy human potential.

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Authors

E. R. Oetting, Ph.D

Jay Webb, M.S.

Tri-Ethnic Center for Prevention Research

Colorado State University

Fort Collins, CO 80523

97

Ethnomethodology,

Psychosocial Measures, and

Inhalant Abuse Research

Joseph E. Trimble

In their chapter, Oetting and Webb set out two fundamental and somewhat

ambitious objectives: (1) to assess and describe the psychosocial correlates of

inhalant use and (2) to recommend a long-term series of highly focused research projects. In this comprehensive chapter, two basic themes subsume the

actual thrust of his work. Specifically, Oetting and Webb emphasize the

science of inhalant abuse research and, to a lesser extent, tantalize the reader

with their emphasis on the role that culture and ethnicity play in the research.

The isolation of these two salient themes stimulated me to focus my comments on selected psychosocial issues and the ethnomethodological1

 flavor of

their writing.

Oetting and Webb, in laying out a progressive series of social and behavioral

science methodological approaches, remain somewhat faithful to their profession. They believe that psychology is a natural science and subscribe to the

1

The term “ethnomethodology” was first coined by Garfinkel (1967) and

refers to the study of the way ordinary people go about their daily lives. In

this chapter, the term has broader implications and broadens the meaning to

include the study of culture from an interdisciplinary perspective.

99
notion that the unit of analysis is the generalized individual. Unlike most of

their colleagues, their perspectives are not locked in a segregationist ideology

where culture is not viewed as a variable worthy of consideration (Pepitone

1987). Oetting and Webb are not steadfast in keeping to the fundamental

guideposts that limit most investigators in the science of the social and behavioral science disciplines. For them culture is an important variable, especially in terms of the methods one chooses to use and the importance of the

unique lifeways and thoughtways of the units of analysis. So it is no surprise

that they recommend ethnographic approaches and devote space describing

inhalant use among different ethnic groups.

Oetting and Webb jump right into the fray of the arguments surrounding appropriate substance abuse research models. They propose a model bounded

by methodological and psychosocial dimensions. As intended, the model

prompts close scrutiny and begs for analysis. The bait is not easily ignored.

The methodological dimension follows a linear progression marked by presumed increasing scientific rigor. They note that scientific inquiry begins with

naturalistic observations and ends with treatment research. The progressive

dimension resembles the levels of analysis perspective introduced by the sociologist Talcott Parsons (1960) and advanced by the social psychologists Sherif

and Sherif (1969).

The methodological dimension prompts me to make a few pointed suggestions. First, I would argue that the ethnographic method should immediately

follow naturalistic observation; epidemiological procedures tend to be more

quantitative, while ethnography and naturalistic observation lean more to the

use of qualitative procedures. In fact, the emphasis a researcher places on

quantitative and qualitative procedures fluctuates immensely as one progresses through various levels of research rigor. Second, Oetting and Webb’s

model can be readily expanded and might be made more useful since each

method can be subcategorized into a variety of alternatives. Experimental research, for example, can be subdivided into quasiexperimental studies; this

level of inquiry can be further divided into field studies, natural group experiments, etc. Third, there doesn’t appear to be room in the scheme for economic, historical, physiological, and psychopharmacological methods.

Oetting and Webb might argue that they are preparing a model for psychosocial research, but we cannot lose sight of the obvious fact that psychoactive

substances are chemical compounds that interact with the human body in

varied and complex ways that indeed influence consciousness. And we know

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all too well that each individual reacts to the substances in a multitude of ways

influenced by the history of usage, dosage levels, composition (especially for

solvents) of the drugs, metabolic rates, and the availability of the substance.

Methods are available to isolate the above listed variables. Without these additional methods of inquiry, the methodological dimension is incomplete and

represents only a partial list of those methods necessary to comprehensively

understand and predict the dynamic effects of drug use and abuse. Indeed, by

including the methodological dimension as a psychosocial method, they omit

other important aspects of human behavior.

Unfortunately, the three-part psychosocial dimension consisting of cultural,

social, and psychological elements prompts even more stringent criticism.

The social element presents very few problems and will not be discussed. The

relationship of the psychological element is a bit more confusing. Do Oetting

and Webb really mean the individual? Where is there room for the interactive roles of learning and genetics? What role does the findings of sociobiologists play in the psychological (or individual) element? Should the element be

subdivided into more refined categories to include personality, psychopathology, and development?

The third element, culture, arouses the most concern. Oetting and Webb’s

discussion of culture is somewhat inaccurate and redundant. The social and

psychological elements in the model, in themselves, are not acultural. In the

discussion on culture, Oetting and Webb place the construct in an abstract

domain; they state, “culture provides a foundation of. . .” Culture is a product

and a process, not a foundation. Culture is the result of human interaction

both at the individual and group level and therefore is inextricably woven in

the fabric of all human activity. Furthermore, Oetting and Webb argue that

major socialization forces are based on culture—they are not, as culture permeates those forces in every conceivable manner. For this and many other

reasons I prefer to use the term “enculturation” in lieu of “socialization” as it

is “the aspect of the learning experience which sets (humans) off from other

creatures, and by means which initially and in later life (one) achieves competence . . . within the limits of a given body of custom” (Herskovits, 1948, p. 39).

The concept of culture is fraught with conjecture. Just a cursive review of its

many definitions reveals its complex nature; one can find slightly over 100 attempts to define the seemingly elusive concept. But whatever definition one

chooses, social and psychological processes will somehow be embedded in its

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framework; that is, both processes will be implied by the definition or they

will be stated directly.

Oetting and Webb’s separate listing of culture also raises the inevitable research question: What research variable status should culture be given?

Eckensberger (1979) pointed out that much of the early work in cross-cultural

psychology treated culture as an antecedent and consequently provided no

strategy for the interpretation of culture as a product of human action and

behavioral change. Segall (1983) argues that social and behavioral researchers, rather than strive to comprehend culture, should “identify the various lower-order factors in the natural and man-made environments of humans which influence their behavior in a reliable manner” (p. 127). Hence,

Segall believes that “culture cannot be one of these independent variables” (p.

127). Instead they suggest that it can be given the status of an overarching independent variable. Still others argue that the products of culture should be

dependent variables, and, when that occurs, all sorts of measurement, sampling, procedural, and conceptual problems arise owing to a society’s distinctive lifeways and thoughtways.

The psychosocial model put forth by Oetting and Webb is, however, appropriate for use in outlining a psychosocial research agenda. Because of the

psychosocial domain, the model is somewhat limited in its inclusiveness.

Huba, Wingard, and Bentler (1980) proposed a drug use framework that is a

bit more comprehensive than that proposed by Oetting and Webb. The

model is divided along four progressive dimensions, viz. biological, intrapersonal, interpersonal, and sociocultural. Linkages are established between

various research element domains showing the interrelatedness of factors that

summarily influence drug use. Oetting and Webb’s measurement domains

could be added to those of Huba, Wingard, and Bentler (1980) to add some

guidance for the researcher.

While I have a partial fondness for comprehensive, ecologically grounded

models, they do present horrendous research problems. Drug abuse researchers have been struggling with isolating causal relationships, contingencies, and correlates for decades. Some of the findings make sense; others are

short lived as new, contradictory findings introduce alternative explanations.

Comprehensive models like those proffered by Oetting and Webb and others

are pushing researchers into using a potpourri of variables. We struggle to

balance the precious time we have with our respondents and the number of

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questionnaire items we can conceivably wedge in—each item or set of items is

intended to give clarity to a variable and in some research efforts they end up

as a latent variable in an intricate web of causal vectors in some recursive path

model. As the causal vectors increase, so do our attempts to establish those

significant paths that best predict drug use—in this instance inhalant abuse.

After carefully considering all of the research questions and the model,

Moncher et al. (1990) ended up with a questionnaire containing well over 200

items. The questionnaire, by prearrangement with our sampling units, could

only be administered in a 60-minute session. We had to reduce the number of

items, eliminate scales and variables, and thus erode the pretest reliability of

some of our scales. The painful process of item reduction had to be reflected

against our research agenda, commitments to research sponsors, and the integrity of our scientific mission. Some critics would argue that any predictive

model we generated from our results would be only partially valid since there

are many potent sources of causality that could not be included in our study.

For example, of necessity we were obligated to ask a series of questions about

polydrug usage—so for each drug (e.g., LSD, heroin, smokeless tobacco,

crack, cocaine, marijuana) we had to repeat a series of interrelated questions

that consumed about 60 percent of our questionnaire. Imagine a drug abuse

study involving just one ethnic group where the researchers are driven to be

inclusive of the many plausible array of interactive variables conducted with a

few of the methods recommended by Oetting and Webb. All things considered, the effort could be enormous.

Few youths experiment with single psychoactive substances such as inhalants

(e.g., solvents). Moreover, youths who integrate drugs into their lifestyle,

however vigorously, usually are using other substances. Attempting single

drug studies can obfuscate the use patterns and the accompanying vicissitudes

of other drug use and argues against single method approaches to studying

drug use. Certainly such isolated studies have merit and are worthy of consideration. As any drug researcher well knows, drug use patterns are not static

phenomena. A temporal and historical factor intrudes on the drug use process that, to a large extent, is molded by changing attitudes, morals, values,

drug availability, economics, and variable social sanctions. In a word, most

drug studies are time bound. What might have been useful data two decades

ago may only have an ounce of relevance for the last decade of the 20th century. To prevent our results from wearing out, do we wear out ourselves and

our respondents by designing massive data mining ventures to accumulate and

generate as much information as possible?

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Oetting and Webb’s chapter, especially the well written and thorough literature review, raises even more painful questions. A number of themes and

findings could be isolated for further discussion; in keeping with the theme of

this reply, emphasis will be directed toward the ethnic and cultural results.

Oetting and Webb’s summary of cross-cultural inhalant abuse findings can be

reflected against our review of the ethnic-minority drug abuse literature.

Specifically: (1) drug abuse is presented as more of a problem for nonwhite

ethnic groups; (2) these ethnics become users and abusers in response to the

prevailing disorganization of the social climate; and (3) the study of drug

abuse is only appropriate when comparing use and abuse patterns of different

ethnic groups with whites. Consequently other ethnic groups, especially

blacks, are “overrepresented,” leading to the unfortunate conclusion that

these groups have greater drug use problems than whites (Trimble and Bolek

1989). Moreover, Oetting and Webb’s review and summary also echoes the

review findings of Austin, Johnson, Carroll, and Lettieri (1977) of 13 years

ago. Austin and colleagues maintained ethnic drug abuse research lacked any

cogent theory to explain the results, that interpretations and theoretical generalizations were not convincing, and that the dimensions of the problem

were still not well understood. The two sets of summary statements are not

an indictment of Oetting and Webb’s review; after all they merely organized

and reported what was available to him. Instead, we have a series of psychosocial inhalant abuse findings that actually present more questions than

answers and thus we have large gaps in our understanding of the problem.

One of the problems identified by Oetting and Webb concerns the near absence of studies attempting to isolate the correlates between ethnic and cultural identification of minority youth and inhalant use patterns. Oetting and

Webb do summarize their own work on the identity-use relationship found in

their work among American Indians. By their own admission the results are

both mixed and highly complex. Part of the problem involves the psychometric characteristics of ethnic identification measures and the fact that most

ethnic-minority drug abuse studies fail to assess the levels of ethnic identity of

respondent populations.

More often than not, drug abuse researchers seeking ethnic and cultural explanations select respondents as though they share a common modal understanding of their own ethnicity and nationalistic identification. Oetting and

Webb’s review of the literature bears out this assumption, as does the field of

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ethnic minority substance abuse research. What we find are studies focusing

on American Indians (or Native Americans), Asian and Pacific Americans,

Blacks, Mexican Americans, Puerto Ricans, and even studies involving

“Hispanics” (Trimble 1991). For a vast majority of the studies descriptions of

ethnics tend to rely on the use of broad ethnic glosses, superficial, almost vacuous, categories that serve only to separate one group from another. Use of

such glosses gives little or no sense of the richness of cultural variations

within these groups, much less the existence of numerous subgroups characterized by distinct lifeways and thoughtways. Forbes (1990) maintains that

use of broad ethnic designations in any form is insulting. Heath (1987) offers

a more strident observation: “The insult arises from having to deal with someone else with the authority and aggressiveness to assault one’s own ability to

be one’s self” (p. 48). “Even though such gross categories bear no relation to

the reference groups with which people normally identify themselves,” they

claim, “one might expect them at least to yield useful statistics at the national

level. Unfortunately, they are utterly useless in that respect as well” (p. 106).

Use of ethnic glosses to conduct ethnic-comparative or ethnic-specific studies

is not only insulting, it is very poor science. Consider the implications for external validity and replication studies (of which there are very few indeed in

the drug abuse field).

So how do we assess ethnic-identity and marginality? The latter is a related

construct that Oetting and Webb identified as a major theme. Most importantly, respondents should be given the opportunity to self-identify, a point

emphasized by Trimble (1991) and Forbes (1990). Measuring ethnicity, however, “is not a simple all or nothing proposition. Researchers have long recognized that a person’s level or intensity of identification with a particular

ethnicity can vary from a weak-nominal association to a strong-committed

association” (Smith 1980, p. 79).

Admittedly somewhat contradictorily in light of previous comments, I am

recommending that ethnic identification be the mainstay of all studies involving ethnic groups. Self-identification by itself is not sufficient since it creates yet another variation of the ethnic gloss. Measures (which mean more

questionnaire items and therefore more time) should tap into the depth and

subtle layers of one’s ethnicity. As a possibility I suggest that the tripartite

measurement domains depicted in figure 1 serve as a guide. As currently

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Figure 1. Ethnic identification measurement domains
conceived, ethnic identity consists of the subjective, behavioral, and natal domains. Suitable variables are listed beneath each domain that when aggregated across the measures would yield a unified index. Respondent indices

most likely would vary across a continuum. Such variation permits numerous

statistical manipulations not otherwise available to the researcher who uses

ethnic glosses. Moreover, strong, reliable ethnic identification measures

would increase external validity, offering the field a more valid array of

findings (Trimble 1991).

Marginality, while an interesting concept, has not received the benefit of a

good deal of research. That is, there are very few scales to assess it. In part,

marginality is really a component of the acculturative process as determined

by social class, socioeconomic status, ethnicity, and a few other salient but distinguishing characteristics. Oetting and Webb’s claims that inhalant users are

found among the marginal ones at any age and in any group and “are marginal

in society” need more substantiation. Gist and Wright (1973) maintain that

groups are marginal when: (1) members do not ordinarily qualify for admission into another group with which it is more or less closely associated; (2)

these groups differ significantly in the nature of their cultural or racial heritage; and (3) between them there is limited cultural exchange or social interaction. Are there empirical data available to demonstrate indeed that

inhalant users are marginal? Are some users more marginal than others?

Can some form of intervention strategy be devised to chip away at the social

and psychological factors that contribute to marginality? Are the users

perennially marginal or do they sense their marginality when they feel excluded from groups to which they aspire to affiliate? Inhalant users may be at

the edge, but it seems to me that some sense of belonging occurs through peer

clustering and the correspondent use of inhalants and presumably other

drugs. Scales should be developed to assess the marginality hypothesis. The

continued use of the term without adequate substantiation provides the field

with a thin excuse to explain away the problem.

Finally, I want to draw some attention to the notion that inhalant and polydrug users have something wrong with their sense of self. Many lay people

and some researchers seem to be firmly committed to the idea that when

youths use drugs, there one will find a distorted, negatively imbalanced relationship between ideal self and real self. Oetting and Webb did not find many

studies examining the self-ideal notion among inhalant users. The ongoing

drug use research being conducted at the National Center for American

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Indian and Alaska Native Mental Health Research, which was conducted at

an American Indian boarding school, yielded no significant statistical relationship for a measure of self-esteem and drug use (S. Manson, personal

communication). In fact, self-measures are weak predictors in their regression analyses. Moreover, Moncher et al. (1990) found similar results among

Indian youths in the State of Washington. Other researchers, too, have and

continue to get mixed results in their studies relating self-perception or regard

to the causes, prevention, and intervention of drug use. There may be a relationship. However, if we are going to continue to explore its possibilities, a

good deal of solid psychometric research should be conducted. First, most

drug researchers do not use the same measures of self. What is most often

used are variations of Rosenberg’s self-esteem scale. Hence, researchers are

encouraged to settle on using comparable measures of self. Second, the concept of self is extraordinarily complex. Therefore, research is needed to isolate what self domain (e.g., esteem, understanding, control, alienation, mattering, acceptance, efficacy) is most associated with drug use. Third, we can

no longer accept drug-related self-study results that are based on very short

four to eight item scales. Whether the results are significant or not, use of

small item scales tends to obscure observed relationships and general overall

assumptions about the effectiveness of a prevention or intervention modality,

and, in the main, can lead to gross exaggerations of statistically derived mean

effects, especially if one has large samples. And, finally, a concerted, concentrated effort is needed to explore the theoretical relationship between the

sense of self and what drug use really does to the general personality makeup

of users. I have never quite understood why someone who ostensibly feels

good about one’s self would use a consciousness altering substance that would

enhance that feeling.

References

Austin, G.A.; Johnson, B.D.; Carroll, E.E.; and Lettieri, D.J., eds. Drugs and

Minorities. Research Issue 21. Rockville, MD: National Institute on Drug

Abuse, 1977.

Eckensberger, L.H. A metamethodological evaluation of psychological theories from a cross-cultural perspective. In: Eckensberger, L.H.; Lonner,

W.J.; and Poortinga, Y.H., eds. Cross-Cultural Contributions to

Psychology. Lisse: Swets and Zeitlinger, 1979. pp. 255-275.

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Forbes, J.D. The manipulation of race, caste and identity: Classifying

Afroamericans, Native Americans and red-black people. J Ethnic Studies

17(4):1-51, 1990.

Garfinkel, H. Studies in Ethnomethodology. Englewood Cliffs, NJ: PrenticeHall, 1967.

Gist, N. and Wright, R. Marginality and Identity. Leiden: Brill, 1973.

Heath, D.B. Anthropology and alcohol studies: Current issues. Ann Rev

Anthropol 16:99-120, 1987.

Hcrskovits, M.J. Man and His Work: The Science Of Cultural Anthropology.

New York, NY: Knopf, 1948.

Huba, G.J., Wingard, J.A., and Bentler, P. Framework for an interactive theory of drug use. In: Lettieri, D.J.; Sayers, M.; and Pearson, H.W., eds.

Theories on Drug Abuse: Selected Contemporary Perspectives. Research

Monograph 30. Rockville, MD: National Institute on Drug Abuse, 1980.

pp. 95-101.

Moncher, M.; Holden, G.; and Trimble, J. Substance abuse among NativeAmerican youth. J Consult Clin Psychol 58:400-415, 1990.

Parsons, T. Structure and Process in Modem Societies. New York: Free Press,

1060.

Pepitone, A. The role of culture in theories of social psychology. In:

Kagitcibasi, C., ed. Growth and Progress in Cross-Cultural Psychology.

Amsterdam: Swets & Zeitlinger, 1987. pp. 12-21.

Segall, M. On the search for the independent variable in cross-cultural psychology. In: Irvine, S.H., and Berry, J.W., eds. Human Assessment and

Cultural Factors. New York: Plenum, 1983. pp. 127-137.

Sherif, M., and Sherif, C. Social Psychology. New York: Harper and Row,

1969.

Smith, T.W. Ethnic measurement and identification. Ethnicity 7:78-95, 1980.

Trimble, J.E. Ethnic specification, validation prospects and the future of substance abuse research. Int J Addict, 1991.

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Trimble, J.E. and Bolek, C.S. “Ethnic Minority Substance Abuse Research

Perspectives: A Literature Review With Commentary.” Paper presented

at a conference sponsored by the National Institute on Drug Abuse on

the topic of conducting cross-cultural substance abuse research,

Rockville, MD, May 1989.

Author

Joseph E. Trimble, Ph.D.

Center for Cross-Cultural Research

Department of Psychology

Western Washington University

Bellingham, WA 96225

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Comments on

Psychosocial Characteristics

Daniel L. Creson

In clinical work with individuals who use and, in society’s term, “abuse” street

drugs (an interesting euphemism in itself), I am often reminded of George E.

Valliants’ words, used in a different context:

If you have not the strength to accept the terms life offers you,

you must in self-defense, force your own terms upon it

(Valliants 1977).

This maxim is not unlike that of a 14 year-old inhalant user who said, in response to my persistent curiosity, “Man, look, me and my friend do what we

do and that’s just the way it is.”

I don’t know what Vaillants meant by the word “strength” when he referred to

“strength to accept the terms life offers you.” It is most certainly a subjective

attribute, one that in human terms is needed to provide reason for why some

individuals behave in one way and others in a very different way, why some individuals use inhalants as a mode of forcing their own terms on life, and others, from the same neighborhood, the same schools, and with similar experiences, do not. My inhalant using young friend chose a concept different than

Valliants, but one just as deterministic. The use of inhalants was what he did,

but was more than that—it was what he did with his friend.

For researchers, “That’s just the way it is” and even “That’s just the way it is

with me and my friend” is just a beginning. Oetting and Webb have traced the

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paths of researchers in their attempts to go beyond that beginning. In their

comprehensive and exhaustive review of the inhalant abuse literature as we

refer to it, they have described a multiplicity of variables that correlate with

the use of inhalants, a multiplicity that is remarkably uniform from study to

study. There are a few surprises—but not many. In the process of this review,

inadvertently or perhaps with a clear intent, Oetting and Webb have done

something more. They have uncovered something about the way the social

scientist thinks about inhalant abuse. The evidence is indirect, but no more

so than most social anthropological evidence. Oetting and Webb have given

us some idea of our own preconceptions as they are implicit in: (1) the

questions we ask about the use of inhalants, (2) the words and concepts we

use in forming those questions, (3) the way those questions are asked, and (4)

the sense we attempt to make out of the answers.

It may be that our mode of thinking presupposes a nonexistent smoking gun.

The research literature Oetting and Webb have so carefully surveyed fails to

disclose such an obvious linear cause-and-effect relationship that would make

other questions redundant. I doubt seriously that they expected to find such

an ultimate answer. Nor do I believe that anyone in this field is seriously

committed to the idea that such a solution is possible.

As a direct result of these preconceptions, and sometimes even despite our

own awareness of our own preconceptions, we continue to ask the same questions and, for the most part, get the same answers.

In a recent study of inhalant abuse among adolescents in a low socioeconomic

Hispanic section of Houston, we (Creson and Welch, unpublished) were able

to again confirm the correlations between inhalant abuse and such variables

as (1) poor school performance, (2) high school dropout rates, (3) disciplinary

problems, (4) polydrug use, and (5) peer influences.

I believe this incremental and conformational process of repeated similar

findings is valuable, but I believe that Oetting and Webb’s call for a comprehensive research strategy is much more important—and certainly more exciting. The elegant and sophisticated model they propose has much to recommend it. There are problems, however, and one of these Oetting and Webb

recognize and define. It is a problem of resources. There is also a second

problem, a problem of complexity.

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With regard to resources, it seems unlikely that the talent and financial support are available for allocation to such a research effort, given the multiplicity of human dilemmas that social scientists are being asked to unravel. To

provide such resources over time as they become available would be impractical. The time frame for the research effort could not be endlessly extended.

In the rapidly changing social/cultural context of contemporary human life,

research needs to be completed in a period during which previous findings

remain relevant.

I do not believe Oetting and Webb meant the schema they proposed to be a

road map, but rather a model for structuring our thinking, and in this way, it is

extremely helpful. It is in this context that the second problem arises. It has

to do with the necessary complexity the task requires. There are omitted parameters from their schema that must, at some point, be evoked if the schema

is to organize rather than restrict our thinking. One can, for example, postulate additional second or third order categories of social variables, such as

political and economic dimensions.

Further, and more importantly, the reciprocity between environment and biology, the consequences of social life acting on genetic potential, and the mediation of such feedback, all loop through an evolving awareness of self with

attendant values and personas that contain implicit behaviors in given specific

contexts. These complexities provide the greatest potential for useful understandings of why some use inhalants and others do not.

A recent incident puts this in perspective. A staff discussion of demographic

and test data collected in a previous study (Creson and Welch, unpublished)

left me dissatisfied, feeling that we had not significantly increased our understanding of what was going on in the youth culture of the Hispanic community

in which we were working. The most significant finding was the results of

neuropsychological testing of our inhalant abusing subjects. A striking finding to us was the discrepancies between performance and verbal I.Q.s in the

inhalant abusing groups, where performance I.Q.s were significantly higher

than in the noninhalant abusing group. The testing data were incongruent

with our structured way of thinking about the problems. The demographic

data were not.

Then I read Oetting and Webb’s paper. My first thought was that only a

prospective study could get us beyond what seemed to me to be a conceptual

road block and clarify the interrelationship between the biological (presuming

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the I.Q. discrepancies to be in some degree a function of biological and sociological interaction), and the social demographic data. But I have had some

subsequent thoughts, less grandiose, but ones I want to share.

Paul Watzlawick wrote, “The belief that one’s own view of reality is the only

reality is the most dangerous of all delusions” (Watzlawick 1976). That

thought is not a new one. It is not new to mystical speculation, and it is not

new to scientific investigation.

The belief that substance abuse (in this case, the use of inhalants) “is ‘caused’”

is at the basis of much of the research that has been done. The very word

“abuse” makes the assumption explicit. Richard A. Meisch (author of a chapter in this volume) once said to me, “What is amazing is that we are not all cocaine addicts.” Much the same might be said about inhalants. Instead of exclusively looking for profound influences in the social cultural environment

that predispose one to the use of inhalants, perhaps we should allocate some

of our resources to an investigation of what may well be (based on animal

studies) the abnormal state of “nonuse”. It seems probable that the cause of

nonuse can most profitably be pursued in the interaction of socio/cultural

variables and biological processes. (Demographics interacting with the biological antecedents of I.Q. discrepancies).

It is impossible for science to answer all the questions that human creativity

can formulate about inhalant abuse. Many of them would be nonsensical and

beyond any answer. Most of them would be semantic puzzles rather than substantive issues. For this reason, scientific research strategies are necessary,

and the first step in an existence of shifting reality is to ask what does one

want to accomplish. This in no way negates basic research. Basic research

goes where no one has gone before (or perhaps only a few). It is not basic research to ask the same questions others have often asked in another place, or

with another group. In no way meaning to disparage replicating investigations, (our own included), it seems probable that there are other questions

that might be assigned a higher priority.

It seems to me that a major motivation for asking questions about inhalant

use is a desire to accomplish something, i.e., reduce the use of the inhalants.

If this is accurate, then I would propose that direction (goal or goals) also be

incorporated into Oetting and Webb’s schema, that there be a measurable end

point. One might propose a trial of successful interventions directed at social

problems other than inhalants. The sophisticated targeted merchandising

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strategies used to reduce HIV infection in the gay community of San

Francisco might, for example, be directed against inhalant use in a defined

population. This would fall into Oetting and Webb’s category of experimental research, but the preimplementation merchandising surveys and trial

would facilitate a more creative traditional research effort, including providing an impetus for studying the ethnologies that Oetting and Webb point out

are missing from the literature.

Oetting and Webb’s chapter is important. In it: (1) they provide us with a

useful and thorough survey of relevant research, (2) underscore some of the

prevalent research biases, (3) provide one heuristic model for conceptualizing

future research, and, more importantly, (4) give us a basis for a stimulating

and creative discussion that cannot help but improve our collective approach

to find a better and more useful way of understanding the behaviors involved

in the use of inhalants.

References

Creson, D.L., and Welch, G. Unpublished.

Valliants, G.E. Adoptation to Life. Boston: Little Brown, 1977.

Watzlawick, P. How Real is Real? New York: Random House, 1976.

Author

Daniel L. Creson, M.D., Ph.D.

Mental Sciences Institute

University of Texas

1300 Moursund Avenue

Houston, TX 77030

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Solvent Toxicity:

A Neurological Focus

Neil L. Rosenberg

Charles W. Sharp

Toxicology of Inhalant Abuse

Acute Intoxication

Most commercial products that are inhaled contain several distinctly different

solvents, each with its own potential distinct toxicity. In addition, most

“inhalant abusers” have inhaled a variety of products to excess before they appear in a treatment facility. One exceptional case would be a novice experiencing an overdose—usually resulting in anoxia and possibly death. The

majority of inhalant abusers never reach a hospital or outpatient facility.

Many inhalant abusers use one or two “preferred brands,” but this will change

according to availability. For example, in the inhalant-abusing population in

Denver, a clear spray lacquer of a particular company was the favored inhalant. However, when it became evident that the main use of this product

was to get high, it quickly disappeared from store shelves. The inhalant-abusing population just as quickly focused their attention on a particular gold

spray paint as the preferred brand.

To understand the solvent abuser, one can conceive of the intoxicated state as

a quick “drunk,” as many of the symptoms resemble alcohol intoxication.

These individuals display several of the following symptoms: initial excitation

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turning to drowsiness, disinhibition, lightheadedness, and agitation. With increasing intoxication individuals may develop ataxia, dizziness, and disorientation. In extreme intoxications, they may show signs of sleeplessness, general

muscle weakness, dysarthria, nystagmus, and occasionally hallucinations or

disruptive behavior. Several hours after, especially if they have slept, they are

likely to be lethargic, hung over with mild to severe headaches. Chronic abuse

is associated with more serious complications including weight loss, muscle

weakness, general disorientation, inattentiveness, and lack of coordination.

Most reports have described the acute intoxication in heavy users of toluene

vapors. Acute intoxication with toluene produces headache, euphoria, giddiness, and cerebellar ataxia. At lower levels (just over 200 ppm), fatigue,

headache, paresthesia, and slowed reflexes appear (Benignus 1981; Von

Oettingen et al. 1942). Exposure to levels over 600 ppm causes confusion or

delirium, and euphoric effects appear above 800 ppm. Although solvent

abusers have favorites, occasionally they use an unpredictable array of solvents. Multiple components in the mixtures may enhance the net toxicity in a

synergistic or additive manner. More specific syndromes and details of the

clinical features of the chronic inhalant abuser are described below and are

related as closely as possible to specific substances.

General Considerations

Although treatments are usually not specific or designed for different solvents, it is important to identify the major contributing factors in understanding the prognosis and recovery of the individual and in the design of

treatment. This is not easy, as it is difficult to identify the causative agents

even if one obtains the container or product most often used.

Labels are often insufficient to identify even the major, let alone any minor

elements, that could be contributory to the disease state. It is also common

for the labels to identify toluene and some other solvents but yet ignore other

substances. For example, one of the more toxic agents, hexane, affects the peripheral nervous system and has been identified in products that did not list it

on the product’s label. Only through an analysis of the products used (e.g., by

quantitative gas chromatography) will it be possible to determine most of the

volatile solvents in a product. Further, identification of one product sniffed

by the user does not reveal all the toxicants that should be considered in the

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user’s diagnosis. A “sniffer’s” repertoire is quite varied in the type of solvents

as well as other drugs used.

In anticipation that the physician, forensic toxicologist, or others will be able

to identify the major substances contributing to the disease state, we will attempt here to delineate the symptoms most often encountered in inhalant

abusers and hopefully on a rational basis correlate them where possible with

the substances that are most likely to be the cause. We will include where

possible any specific treatments that will be used in addition to the provision

of the usual basic supportive care.

To correlate those specific clinical symptoms that result from exposure to

various volatile chemicals is not easy, as suitable animal studies have not corroborated many clinical evaluations. Also, months to years of exposure are

often necessary for the expression of some disease states. As many inhalant

abuse subjects are not admitted to hospitals, outpatient clinics, or drug treatment program for problems associated with inhalant abuse overdose or dependency, little information has surfaced detailing many of their problems.

Therefore, this review will utilize clinical epidemiological studies of noninhalant abusers as well as retrospective clinical case studies of inhalant abusers

and other solvent-related accidents, whether from abuse or occupational exposures, along with the information derived from animal studies, to identify

particular hazards that may result from inhalation exposure.

Recognition of and Criteria for Defining Neurotoxicity

The nervous system may be affected at many levels by organic solvents as well

as other neurotoxic substances. As a general rule, resultant syndromes are

diffuse in their manifestations (Schaumburg and Spencer 1987). Because of

their nonfocal presentation, neurotoxic disorders may be confused with

metabolic, degenerative, nutritional, or demyelinating disease (Schaumburg

and Spencer 1987). This principle is illustrated in the setting of chronic

toluene abuse, which may resemble the multifocal demyelinating disease, multiple sclerosis, in the findings on neurological examination (Lazar et al. 1983;

Hormes et al. 1986; Fornazzari et al. 1983). In addition, neurotoxic syndromes rarely have specific identifying features on diagnostic tests such as computed tomography (CT), magnetic resonance imaging (MRI), or nerve conduction studies (Schaumburg and Spencer 1987). As a result, mild cases of intoxication may be very difficult to diagnose. The most reliable information, in

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fact, comes from documented cases of massive exposure, and details of low

level exposure and presymptomatic diagnosis are vague at best.

Acute, high-level exposure to most, if not all, solvents will induce short-lasting effects on brain function, most of which are reversible. Acute incidents

that are irreversible probably act by producing secondary systemic effects such

as cerebral hypoxia or a metabolic acidosis (Rosenberg 1992) and none have

been proved to act by inducing an irreversible functional abnormality. In general, both acute high-level and low-level exposure to organic solvents are associated with full reversibility, and the acute toxicity with high-level exposure

in no way predicts whether chronic low-level exposure will lead to an irreversible neurological disease.

Chronic high-level exposure to organic solvents occurs only in the inhalant

abuse setting, where levels several thousand fold higher than the occupational

setting occur frequently. Chronic neurotoxic disease related to solvent abuse

is slowly and incompletely reversible, is usually irreversible, and usually does

not progress after cessation of exposure (Hormes et al. 1986, Fornazzari et al.

1983). Both acute and chronic neurotoxicity from organic solvents are functions predominantly related to the dose and duration of exposure.

There may be no relationship between the mechanism of acute neurotoxicity

and the clinical manifestations of chronic neurotoxicity. For example, an

acute effect of a particular organic solvent may be attributable to the parent

compound, while a chronic effect may be associated with a metabolite of this

compound. In addition, in several known cases, a solvent has been reported

to either diminish or potentiate the neurotoxic potency of a second solvent

(Altenkirch et al. 1982; Altenkirch et al. 1977; Saida et al. 1976).

There is little or no apparent individual variability or altered susceptibility to

the neurotoxic effects of either acute or chronic exposure to organic solvents.

Except for other toxic exposures or illnesses that also cause neurologic sequelae, individuals will be likely to develop a similar clinical picture when exposed to solvents at equivalent doses for equivalent durations of time.

Chemical structure usually does predict the neurotoxic effects. An example of

this is seen with two closely related compounds: 2,5-hexanedione (the toxic

metabolite of n-hexane) and 2,4-hexanedione. A fixed dose of 2,5-hexanedione produces axonal degeneration in a particular species very similar to that

produced by hexane, whereas 2,4-hexanedione never produces these changes.

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Thus a small but important change in the compounds structure elicits a

change from a positive to a negative pharmacological action.

Treatment of the Inhalant Abuser

There is no accepted treatment approach for inhalant abusers. Many drug

treatment facilities refuse treatment of the inhalant abuser, because many feel

that inhalant abusers are resistant to treatment. In general, it is felt that

longer periods of treatment are needed to be able to address the complex psychosocial, economic, and biophysical issues of the inhalant abuser. When

brain injury, primarily in the form of cognitive dysfunction, is present, the rate

of progression in the treatment process is even slower.

The inhalant abuser typically does not respond to usual drug rehabilitation

treatment modalities. Several factors may be involved, particularly in situations of the chronic abuser, where significant psychosocial problems may be

present. Treatment becomes slower and progressively more difficult when the

severity of brain injury worsens as abuse progresses through transient social

use (experimenting in groups) to chronic use in isolation.

Drug screening may be useful in monitoring inhalant abusers. Routine urine

screens for hippuric acid (the major metabolite of toluene metabolism) performed two to three times weekly will detect the high level of exposure to

toluene usually seen in inhalant abusers.

Neuroleptics and other forms of pharmacotherapy are usually not useful in

the treatment of inhalant abusers. However, as alcohol is a common secondary drug of abuse among inhalant abusers, a monitored program for

alcohol abuse may be necessary.

Neurological Sequelae of Chronic Inhalant Abuse

Organic solvents are widely prevalent compounds and inadvertent exposure,

primarily industrial, as well as volitional abuse occurs primarily by inhalation,

with significantly less absorption occurring via skin or gastrointestinal routes.

These compounds are highly lipophilic, which explains their distribution to

organs rich in lipids (e.g. brain, liver, adrenal). Unexpired solvents absorbed

by the tissues are then eliminated through the kidneys following metabolism

of the solvents to more water-soluble compounds. In addition, metabolism of

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some solvents may create additional compounds that are sometimes more

toxic than the parent chemical (Allen 1979; Goetz 1985; Spencer and

Schaumburg 1980).

Although most organic solvents produce nonspecific effects following absorption of extremely high concentrations (i.e., encephalopathy), a few produce

relatively specific neurologic syndromes with low level, chronic exposure.

Table 1 lists those syndromes associated with organic solvent exposure. Most

of the early animal studies, which served as the basis for the setting of tolerance levels in industry, utilized acute studies to measure the effects, often including high level exposures that produced lethality. More recent clinical and

experimental studies have focused on chronic low-level exposures to solvents

that result in slowly developing peripheral and central nervous system syndromes. Two major neurotoxic syndromes occur in individuals chronically

exposed to select organic solvents: a peripheral neuropathy and an encephalopathy. Less commonly, a cerebellar ataxic syndrome, parkinsonism, or

a myopathy may occur alone or in combination with any of these clinical syndromes. In some instances, solvents interact and cause synergistic effects,

resulting in multifocal central and peripheral nervous system damage.

As noted above, many organic solvents are, at high levels of exposure, capable

of inducing an acute, reversible encephalopathy. Few induce chronic, longlasting, or irreversible changes in nervous system structure and/or function.

For organic solvents with proven neurotoxic properties, the type of neurological damage is often closely related to the structure of the chemical agent,

while the degree of impairment and the extent of reversibility are related to

the potency, dose, and duration of exposure (Spencer and Schuamburg 1985).

Examples include n-hexane and methyl butyl ketone, which produce peripheral neuropathy, both related to voluntary inhalation of solvents and accidental exposure in the occupational setting. Chronic inhalation abuse of toluene

produces an irreversible multifocal central nervous system syndrome characterized by dementia, cerebellar ataxia, spasticity, and brainstem dysfunction

(Hormes et al. 1986). However, similar changes have not been found in

workers exposed to toluene in the occupational setting.

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Table 1. Clinical classification of inhalant abusers

Transient Social

Short history of use

Use with friends

Petty offenses while intoxicated

Average intelligence

Possible learning disabilities

10 to 16 years of age

Chronic Social

Long history of use—over 5 years

Daily use with friends

Legal involvement—misdemeanors

Poor social skills

9th grade education

Brain damage

Mid 20s to early 30s

Mental retardation prevalent

Transient Isolate

Short history of use

Use alone

No legal involvement

Average/above intelligence

No learning disabilities

10 to 16 years of age

Chronic Isolate

Long history of use—over 5 years

Daily use alone

Legal involvement—assaults common

Poor social skills

9th grade education

Brain damage

Mid 20s

Pre-use psychopathology prevalent

Solvent Abuse in Occupational Settings

Most studies on the subject of solvent abuse focus on adolescents (Ron 1986).

It has been observed that adults at risk for solvent abuse include those whose

work brings them into contact with these substances, including shoemakers,

painters, individuals working in gas stations, those involved in the refinement

of petrochemicals, degreasers, and others. However, few attempts have been

made to identify the prevalence of solvent abuse in industry. One study reviewed the cases of industrial accidents due to exposure to chlorinated hydrocarbons. Of 384 case of industrial accidents due to either trichloroethylene,

perchloroethylene, or 1,1,1-trichloroethane, nine (2.3 percent) were in individuals identified as habitual solvent abusers by the person investigating the

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accident (Cherry et al. 1982). Although 2.3 percent seems to be a small number, one needs to consider that the number may be much higher, especially in

those industries in which solvents with higher abuse potential (e.g., toluene)

are used, such as in the paint industry. In addition, considering the millions of

individuals exposed to solvents in the workplace, even 2.3 percent represents

a large number of individuals. Finally, when discussing abuse in industry, one

needs to consider issues of personal protection. If an individual worker is instructed on the proper use of protective devices (respirators) on the particular

job being performed, and that individual chooses not to comply, the complaints of injury should be considered self-inflicted (i.e., abuse) rather than

occupational injury, provided the employer has observed its part of the rules

and instructions are in force. This last issue has been ignored in the occupational literature but needs to be addressed in a critical manner in future

studies.

Table 2. Major neurologic syndromes produced by organic solvents

A. Encephalopathy

1. Acute encephalopathy—nonspecific; high level exposure

2. Chronic Encephalopathy—seen with repeated high level exposure

over years

B. Cerebellar ataxia

C. Peripheral neuropathy—distal axonopathy

D. Cranial neuropathy—primarily cranial nerves V and VII

E. Parkinsonism

F. Visual loss—optic neuropathy

G. Multifocal

1. Central nervous system (e.g., toluene)

2. Central and peripheral

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Exposure to organic solvent mixtures either in the occupational or abuse setting is far more common than exposure to a single solvent. Numerous papers,

primarily from Denmark and other Scandinavian countries, allege that

chronic occupational exposure to organic solvents induces irreversible

changes in neurological function that has been described by various terms including psycho-organic syndrome (POS), neurasthenic syndrome, chronic

painters’ syndrome and chronic toxic encephalopathy. This syndrome is characterized by personality change, memory loss, fatigue, depression, and loss of

interest in daily activities, headache, forgetfulness, insomnia, difficulty in concentration, loss of initiative, and depression. Most studies of the POS have

utilized epidemiologic techniques to compare and contrast findings in solvent-exposed and unexposed reference groups. Methods applied have included self-administered questionnaires, neuropsychological tests, and clinical

neurophysiologic and neuroimaging tests. Most reports consider that 10 or

more years of exposure is required to produce the POS; however, one study

has suggested that only a 3-year period may be required (Flodin et al. 1984).

Few papers have even suggested either dose-effect (Gregersen et al. 1984) or

duration-effect (Lindstrom 1980) relationships, obviously critical issues in establishing a toxin-induced syndrome. Virtually all of the studies on this subject have been written by scientists and physicians from Denmark, Sweden,

and Finland, who are of the opinion that organic solvents, as a class, have

chronic neurotoxic properties. In these countries, permanent neurological

deficit of the type described as the POS is a recognized and compensatable

occupational disability. Scientists and physicians from other European and

from North American countries do not recognize this entity and have instead

attempted to understand the chronic effects of individual organic solvents.

Many of these studies were done in a retrospective fashion on individuals already diagnosed as having chronic toxic encephalopathy, psychoorganic syndrome, or solvent poisoning (Seppalainen et al. 1980; Flodin et al. 1984;

Juntunen et al., 1980b; Gregersen et al. 1987; Axelson et al. 1976). The obvious difficulties inherent in any retrospective data analysis are compounded

when individuals have been diagnosed as having the syndrome and often given

disability pensions for this problem.

Reports of this syndrome have been in workers, from various industries where

exposure to solvent mixtures is common including printers (Iregren 1982),

aviation fuel workers (Knave et al. 1979; Knave et al. 1978), and painters

(Iregren 1982; Hanninen et al. 1976; Hane et al. 1977; Linz et al. 1986; Baker

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et al. 1988; Husman and Karli 1980, Husman 1980; Elofsson et al. 1980;

Lindstrom and Wickstrom 1983; Orbaek et al. 1985; Valciukas et al. 1985;

Fidler et al. 1987). Although the majority of reports have focused on symptoms and neuropsychological testing, there have been a few uncontrolled reports showing abnormalities on vestibular function testing (Arlien-Soborg et

al. 1981; Binaschi and Cantu 1983; Hodgson et al. 1989), electroencephalography (Seppalainen et al. 1980; Seppalainen 1973, 1982), electromyography

and nerve conduction testing (Seppalainen 1982; Mutti et al. 1982), visual

evoked potentials (Seppalainen 1982; Elofsson et al. 1980), cerebral blood

flow (Hagstadius and Risberg 1983; Arlien-Soborg et al. 1982), pneumoencephalography (Juntunen et al. 1980a) and computed tomography (Jensen et

al. 1984) in both symptomatic and asymptomatic individuals.

However, recent studies have begun to cast doubt as to whether long-term occupational exposure to solvents causes any permanent neurological dysfunction (Grasso et al. 1984; Errebo-Knudsen and Olsen 1986; Juntunen et al.

1985; Triebig et al. 1988; Gade et al. 1988; Errebo-Knudsen and Olsen 1987).

A detailed review of this current literature does not support previously published studies relating chronic occupational solvent exposure to any permanent central or peripheral nervous system injury. Occupational solvent exposure literature discusses the inadvertent exposure of an individual to these

compounds; however, the issue of abuse of these substances in the workplace

is also of concern.

Specific Compounds of Interest

The listing of organic solvents, which are described in detail below, is not intended to be a complete listing of compounds with associated neurotoxicity.

Represented are those organic solvents that have been more commonly associated with abuse or where clear neurotoxicity is associated with exposure.

N-hexane and methyl butyl ketone. These two organic solvents are classified together because both n-hexane and methyl butyl ketone (MBK) are metabolized to the same neurotoxin, 2,5-hexanedione (2,5-HD) and produce a similar

peripheral neuropathy. 2,5-HD is responsible for most, if not all, of the neurotoxic effects that follow exposure to n-hexane or MBK (Spencer and

Schaumberg 1980; Spencer et al. 1980; Graham et al. 1982; Perbellini et al.

1981). Methyl ethyl ketone (MEK) alone produces neither clinical nor

pathologic evidence of a peripheral neuropathy in experimental animals

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(Spencer and Schaumberg 1980). MEK’s importance is related to a synergistic effect between MEK and MBK and MEK and n-hexane detected in experimental animals and probably in humans (Altenkirch et al. 1982;

Altenkirch et al. 1977; Saida et al. 1976). This potentiation of toxicity of one

compound (MBK or n-hexane) by an otherwise nontoxic compound (MEK)

underscores the difficulty with sorting out toxic effects of individual solvents

contained within a mixture, and suggests that occupational exposure to solvent mixtures should be minimized or avoided altogether.

Methyl butyl ketone. MBK had limited industrial use until the 1970s, when it

became more widely used as a paint thinner, clearing agent, and a solvent for

dye printing. Soon afterward, numerous outbreaks of polyneuropathy associated with chronic exposure to MBK were being reported (Menkes 1976;

Billmaier et al. 1974; McDonough 1974; Allen et al. 1975; Mallov 1976).

Originally, MEK had been used as a solvent, followed by a mixture of MEK

(90 percent)/methyl isobutyl ketone (10 percent). When the methyl isobutyl

ketone was replaced by MBK (10 percent), reports of polyneuropathy began

to appear in the literature. The route of exposure is usually inhalation, but

the oral route has also occurred by ingesting contaminated food in work areas,

and cutaneous contact has also occurred.

The clinical syndrome is characterized by the insidious onset of an initially

painless sensorimotor polyneuropathy, which begins several months after

continued chronic exposure. Even following cessation of exposure, the neuropathy may develop or may continue to progress for up to 3 months. In severe cases an unexplained weight loss may be an early symptom. Sensory and

motor disturbance begins initially in the hands and feet, and sensory loss is

primarily small fiber (i.e., light touch, pin prick, temperature) with relative

sparing of large fiber sensation (i.e., position and vibration).

Electrophysiologic studies reveal an axonal polyneuropathy and pathologically multifocal axonal degeneration, multiple axonal swellings, and neurofilamentous accumulation at paranodal areas (Spencer et al. 1975). Overlying

the axonal swellings, thinning of the myelin sheath occurs. These findings are

typical of a distal axonopathy or “dying-back” neuropathy described in other

toxic and metabolic causes of peripheral neuropathy.

Prognosis for recovery correlates directly with the intensity of the neurologic

deficit before removal from toxic exposure, with mild to moderate residual

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neuropathy seen in the most severely affected individuals up to 3 years after

exposure.

N-hexane. Until relatively recently, n-hexane has been considered an innocuous solvent. N-hexane is used in the printing of laminated products, extraction of vegetable oils, as a diluent in the manufacture of plastics and rubber,

in cabinet finishing, as a solvent in biochemical laboratories, and as a solvent

for glues and adhesives.

Cases of n-hexane polyneuropathy have been reported both after occupational exposure (Herskowitz et al. 1971) and after deliberate inhalation of vapors from products containing n-hexane, such as glues (Gonzales and Downey

1972; Shirabe et al. 1974; Goto et al. 1974; Prockop et al. 1974; Korobkin et

al. 1975; Oh and Kim 1976; Towfighi et al. 1976). Clinically and pathologically, the neuropathy occurring with n-hexane is that of a distal axonopathy

(Schaumburg and Spencer 1976), indistinguishable from that associated with

MBK.

When glues have been analyzed in past reports of polyneuropathy occurring

after glue sniffing, n-hexane has been a major component of the products’

composition (up to 50 percent by weight). Another major component of

these glues has been toluene; however, polyneuropathy does not occur from

inhalation of toluene alone, and in previous reports of n-hexane neuropathy,

the neuropathy did not appear until the subject switched to a product containing n-hexane. In contrast to toluene, n-hexane does not usually induce

significant signs of central nervous system dysfunction, except with high-level

exposures where an acute encephalopathy may occur.

Both clinical and experimental studies have shown evidence of central nervous system effects from n-hexane. Experimental animal studies have shown

n-hexane to cause axonal degeneration in the central nervous system

(Schaumburg and Spencer 1976; Frontali et al. 1981). Clinically, cranial neuropathy, spasticity and autonomic dysfunction occasionally occur (Altenkirch

et al. 1982). Abnormalities on electrophysiologic tests of central nervous system function have also been seen, including electroencephalography, visual

evoked responses, and somatosensory evoked responses (Seppalainen et al.

1979; Mutti et al. 1982). In spite of these finds, clinical effects of chronic low

level exposure to n-hexane is restricted to the peripheral nervous system.

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Toluene (methyl benzene). Toluene is one of the most widely used solvents and

is employed as a paint and lacquer thinner, and as a cleaning and drying agent

in the rubber and lumber industries, and in the motor and aviation fuels and

chemical industries. It is a major component in many paints, lacquers, glues,

and adhesives, inks and cleaning liquids. As with other solvents, inhalation is

the major route of entry, though some absorption occurs percutaneously. Of

all the solvents, toluene-containing substances seem to have the highest potential for abuse (Press and Done 1967; Fredlund et al. 1989; Spence et al.

1989).

In 1961 Grabski reported the first patient with persistent neurological consequences of chronic toluene inhalation. Since then, several reports of severe

neurotoxicity have appeared in the literature (Kelly 1975; Knox and Nelson

1966; Boor and Hurtig 1977; Keane 1978; Sasa et al. 1978; Malm and LyingTunell 1980; Streicher et al. 1981; Takeuchi et al. 1981; King 1982; Metrick

and Brenner 1982; Ehyai and Freemon 1983; Lazar et al. 1983; Fornazzari et

al. 1983; Hormes et al. 1986; Rosenberg et al. 1988a,b).

The effects of chronic exposure are even less well understood than the acute

dose-related neurotoxicity of toluene (Benignus 1981; Von Oettingen et al.

1942). Experience is still not sufficient to determine the incidence or pattern

of chronic effects of toluene and other volatile hydrocarbons. Complete resolution of signs and symptoms has been reported after chronic abuse with

prolonged abstinence and no significant treatment (Boor and Hurtig 1977;

Von Oettingen et al. 1942). Syndromes describing severe and persistent neurotoxicity include cognitive dysfunction (Knox and Nelson 1966; Streicher et

al. 1981; King 1982; Lazar et al. 1983; Fornazzari et al. 1983a,b; Hormes et al.

1986; Rosenberg et al. 1988a,b; Berry et al. 1977; Channer and Stanley 1983;

Tsushima and Towne 1977), cerebellar ataxia (Grabski 1961; Kelly 1975; Boor

and Hurtig 1977; Malm and Lying-Tunell 1980; Streicher et al. 1981;

Takeuchi et al. 1981; Lazar et al. 1983; Fornazzari et al. 1983), optic neuropathy (Keane 1978; Ehyai and Freemon 1983), sensorineural hearing loss (Ehyai

and Freemon 1983), and an equilibrium disorder (Sasa et al. 1978). The most

common syndrome is that of multifocal CNS involvement (Streicher et al.

1981; Metrick and Brenner 1982; Lazar et al. 1983; Fornazzari et al. 1983;

Hormes et al. 1986; Rosenberg et al. 1988a,b). Despite the many instances of

“persistent” neurological deficits, in only one study was abstinence documented prior to clinical evaluation (Hormes et al. 1986). This point is of

great importance, since it has already been noted that some individuals will go

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into complete remission with prolonged abstinence (Boor and Hurtig 1977;

Wiedmann et al. 1987).

In a recent study of 20 chronic abusers of spray paint, which consisted almost

entirely of toluene, abstinence was documented for at least one month prior

to evaluation (Hormes et al. 1986). In these 20 chronic solvent abusers, 65

percent showed neurological impairment. This was a small and unselected

sample, so the findings probably do not reflect the true prevalence of neurologic damage. However, there was a fairly consistent pattern of neurologic

abnormality. As others have suggested, the central nervous system is selectively vulnerable. In fact, no peripheral neuropathy was found, and there is no

convincing evidence that pure toluene or other aromatic hydrocarbons cause

peripheral neuropathy. Aliphatic hydrocarbons such as n-hexane, as noted

earlier, cause predominantly peripheral nerve damage.

Neurologic abnormalities varied from mild cognitive impairment to severe

dementia associated with elemental neurologic signs such as cerebellar ataxia,

corticospinal tract dysfunction, oculomotor abnormalities, tremor, deafness,

and hyposmia. Cognitive dysfunction was the most disabling and frequent

feature of chronic toluene toxicity and may be the earliest sign of permanent

damage. Dementia, when present, was typically associated with cerebellar

ataxia and other signs (Hormes et al. 1986).

Other investigators have found a similar syndrome after chronic exposure to

toluene (Boor and Hurtig 1977; Malm and Lying-Tunell 1980; Lazar et al.

1983; Fornazzari et al. 1983). Although some emphasized the cerebellar disorder, most cases also showed that they were impaired in a variety of cerebral

functions. In one study, there was a similar pattern of cognitive impairment

with neurologic abnormality, but the individuals were studied as soon as three

days after the last exposure and there have been no data on long-term cognitive outcome long after cessation of prolonged toluene abuse. It should be

noted, however, that many chronic toluene abusers have had no persistent

cognitive impairment, despite approximately calculated cumulative doses

equivalent to those individuals with cognitive impairment (Hormes et al.

1986; Rosenberg et al. 1988b). This suggests either that the abuse histories

obtained were not accurate or that other factors possibly play a role in those

individuals.

Other types of neurologic dysfunction can be seen in many subjects, especially

pyramidal and cerebellar signs (Hormes et al. 1986). However, in one study,

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this pattern was observed in only one patient who was not also cognitively impaired or demented (Hormes et al. 1986). Oculomotor dysfunction, deafness,

and tremor were seen only in severely affected individuals. Cranial nerve abnormalities were confirmed to olfactory and auditory dysfunction. Tolueneinduced optic neuropathy, previously reported (Keane 1978), was not reported in the larger studies (Hormes et al. 1986; Rosenberg et al. 1988a).

The clinical data suggested that the cognitive, cerebellar, corticospinal, and

brainstem signs are due to diffuse effects of toluene on the central nervous

system. In one prior report of an autopsy of a chronic solvent abuser, there

was prominent degeneration and gliosis of ascending and descending long

tracts with cerebral and cerebellar atrophy (Escobar and Aruffo 1980).

Unfortunately, as in most reports of toluene neurotoxicity, this patient was

abusing many solvents contained in several different mixtures, so the effects of

individual solvents could not be determined.

A recent report has demonstrated that chronic abuse of toluene containing

substances causes diffuse central nervous system white matter changes

(Rosenberg et al. 1988a). This was based on the findings on magnetic resonance imaging (MRI) of the brain in six individuals and the neuropathologic

changes in one abuser not studied by MRI. All individuals abused the same

toluene-containing mixture which contained primarily toluene (61 percent)

and methylene chloride (10 percent). MRI of the six individuals revealed the

following abnormalities: (1) diffuse cerebral, cerebellar, and brainstem atrophy; (2) loss of differentiation of the gray and white matter throughout the

central nervous system; and (3) increased periventricular white matter signal

intensity on T2-weighted images. The brain of the individual studied pathologically revealed diffuse, ill-defined myelin pallor, which was maximal in the

cerebellar, periventricular, and deep cerebral white matter. Neurons were

preserved throughout, axonal swelling or beading was not seen, gliosis was

minimal, and occasional, scant perivascular macrophage collections were

seen. These findings suggest that toluene is a white-matter toxin; the mechanism of action, however, remains to be explained.

Another recent study attempted to find correlation between the severity of

the clinical involvement in 11 chronic toluene abusers and the findings on

brainstem evoked responses (BAERs) and MRI (Rosenberg et al. 1988b).

Neurological abnormalities were seen in 4 of 11 individuals and included cognitive, pyramidal, cerebellar, and brainstem findings. MRI of the brain was

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abnormal in 3 of 11 individuals, and all 3 also had abnormalities on neurological examination. Abnormalities on MRI were the same as those reported

previously (Rosenberg et al. 1988a). BAERs were found to be abnormal in 5

of 11 individuals, and were similar to those previously reported in toluene

abusers (Metrick and Brenner 1982; Lazar et al. 1983). In this study

(Rosenberg et al. 1988b), all three individuals with abnormal MRI scans and

neurological examinations also had abnormal BAERs. Two of five individuals with abnormal BAERs, however, had normal neurological examinations

and MRI scans. This study suggests that BAERs may detect early CNS injury

from toluene inhalation even at a time when neurological examination and

MRI scans are normal. These results also suggest that BAERs may be a sensitive screening test to monitor individuals at risk from toluene exposure for

early evidence of central nervous system injury.

Although an exact dose-effect relationship cannot be drawn yet for chronic

toluene exposure, it is clear that all severely affected individuals have had

heavy and prolonged exposure. The lack of correlation between the type or

duration of exposure and neurologic impairment may be due to unreliable

histories or other factors, such as genetic predisposition (unlikely) or hypoxemia due to huffing or bagging. Nutritional factors and other concomitantly

used substances may also be involved. Gradual resolution of acute toxicity

and absence of withdrawal symptoms were probably due to slow elimination

of toluene from the central nervous system.

Unlike the solvents that cause peripheral neuropathy, such as n-hexane, for

which there are animal models of classical target organ neurotoxicity, no adequate animal model exists for all aspects of toluene-induced neurotoxicity.

Several recent studies have addressed the behavioral effects of both acute and

chronic toluene exposure in laboratory animals (Miyake et al. 1983;

Lorenzana-Jimenez and Salas 1983; Pryor et al. 1983, 1987; Wood et al. 1983;

Rees et al. 1987). Most noteworthy are the studies of Pryor et al., which

demonstrate persistent irreversible high-frequency hearing loss by cued behavioral responses, auditory brainstem evoked responses, and pathology.

This is produced as early as 2 weeks of exposure to 1,200 ppm or 1,400 ppm of

toluene. This was attributed to cochlear dysfunction rather than the central

conduction pathology found in the human studies noted above (Pryor et al.

1983, 1987; Rebert et al. 1983). Other studies from this group have measured

a toluene-induced motor syndrome that is characterized by a widened landing

foot splay and a short and widened gait that may relate to the cellebellar syn132
drome in humans (Pryor et al. 1991). However, as the pharmacodynamics,

distribution, and bioavailability of toluene and its metabolites have been

studied in animals but are poorly understood in humans, the basis for comparing toluene’s effects in experimental animals with those in humans is not

an easy task.

Trichloroemethylme (TCE). TCE is an important organic solvent used extensively

in industry in metal degreasing, extracting oils and fats from vegetable products, cleaning optical lenses and photographic plates, in paints and enamels,

dry cleaning, and as an adhesive in the leather industry. Although its use in

recent years has diminished somewhat due to concern that it could be a human carcinogen (Lloyd et al. 1975), NIOSH estimates the total number of

individuals exposed to TCE to be in excess of 3.5 million (NIOSH 1978).

TCE has been recognized as an industrial hazard with neurotoxic properties

for over 50 years (Feldman 1979). It was once commonly used as an anesthetic agent despite early reports of toxicity (Humphrey and McClelland 1944;

McClelland 1944; Enderby 1944; Firth and Stuckey 1945). TCE, however, was

abandoned as an anesthetic agent, apparently not because of its toxicity, but

because its anesthetic action was weak and eventually better agents became

available (Atkinson 1960). Clinical experience suggested that it was safe in

minimal concentrations, and useful because at the time, it was one of the few

nonexplosive agents that could supplement nitrous oxide and did not produce

significant respiratory depression (Atkinson 1960, Hewer 1943).

The major neurological manifestation is related to a slowly reversible

trigeminal neuropathy (Feldman 1979; Humphrey and McClelland 1944;

McClelland 1944; Buxton and Hayward 1967; Glaser 1931; Defalque 1961a;

Mitchell and Parsons-Smith 1969), although involvement of other cranial

nerves and peripheral nerves have also been described (Feldman 1979;

Gwynne 1969; Feldman et al. 1970). The trigeminal neuropathy associated

with TCE intoxication was recognized as characteristic and for a time intentional exposure was considered a useful treatment of trigeminal neuralgia

(Glaser 1931). Cranial neuropathies were noted after general anesthesia with

TCE over 40 years ago (Humphrey and McClelland 1944; McClelland 1944;

Firth and Stuckey 1945). Of 13 cases of multiple cranial nerve palsies following general anesthesia, 2 were related to TCE anesthesia. Twenty-four to

forty-eight hours after general anesthesia, individuals developed paresthesia

around the lips which then spread to involve the entire trigeminal distribution

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bilaterally over the ensuing 2 to 3 days. Motor weakness also occasionally occurred in the trigeminal distribution and other cranial nerves including facial

(VII) and optic (II) nerves; other lower cranial nerves also became affected

(Feldman 1979; Humphrey and McClelland 1944). Resolution of the

trigeminal neuropathy occurs slowly in an “onion-peel” distribution, felt to be

indicative of segmental or nuclear trigeminal involvement (Feldman 1979;

Feldman et al. 1970).

Most importantly, much of the earlier literature on the neurotoxicity of TCE

includes observations that were most likely due to decomposition products

(e.g., dichloroacetylene) rather than TCE itself (McClelland 1944; Firth and

Stuckey 1945; Defalque 1961b; Waters et al. 1977). Dichloroacetylene, produced most prominently under alkali conditions, reacts violently with air to

produce two noxious gases, phosgene and carbon monoxide (Waters et al.

1977). Dichloroacetylene disrupts the region of the brainstem where the

trigeminal nucleus is located in experimental animals and is therefore probably responsible for the neurotoxic properties of TCE (Schaumburg et al.

1983). Short-term exposure to narcotizing levels of TCE in the industrial setting has also been reported to induce a transverse myelopathy (Sagawa 1973).

This report is of interest because it has also been shown that a transverse

myelopathy can be experimentally induced in the rat with dichloracetate,

which is a possible metabolite of TCE/dichloroacetylene (Spencer and

Bischoff 1982). Attempts to experimentally reproduce the neurotoxicity associated with the industrial use of TCE have not been successful with pure

grades of TCE (Adams et al. 1951; Utesch et al. 1981; Tucker et al. 1982;

Dorfmueller et al. 1979). Recent studies of rats have identified a high-frequency hearing loss similar to that observed for toluene exposure (Rebert et

al. 1991). This is the first study of pure TCE in animals documenting a neurotoxicity that may also be peripheral, i.e., cochlear in origin.

Little data are available on the neuropathologic changes after TCE exposure.

A single autopsied case of an individual who died 51 days after industrial exposure to TCE and TCE decomposition products (probably dichloroacetylene), revealed bilaterally symmetric brainstem lesions (Buxton and Hayward

1967). These changes were most prominent in the fifth nerve nuclei, spinal

tracts, and nerve roots. The fifth nerves both within and outside the brainstem showed extensive myelin and axonal degeneration. Other neuropathologic changes were seen but were less prominent.

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Although higher level exposures to TCE and its decomposition products are

well described, reports of long-term, low-level exposure occurring in the industrial setting are relatively few. These reports have focused on neuropsychiatric and behavioral effects including a neurasthenic syndrome with subjective complaints of dizziness, headache, nausea, fatigue, anxiety, and insomnia

(Andersson 1957; Bardodej and Vyskocil 1956; Grandjean et al. 1955; Lilis et

al. 1969; Salvini et al. 1971; Smith 1970). Although these disorders reportedly

become more severe with length of employment and degree of exposure, the

neurobehavioral and neuropsychological literature on the toxic effects of TCE

is so fragmented and poorly documented that it is impossible to come to any

firm conclusions regarding low-level, chronic exposure to TCE and its neurotoxic potential (Annau 1981). Neurobehavioral disturbances to acute, highlevel exposure have included severe psychiatric presentations (Todd 1954;

Harenko 1967).

Several studies have been performed in order to study the behavioral effects

of single short-term exposure to TCE (Salvini et al. 1971; Stewart et al. 1970;

Ferguson and Vernon 1970; Winneke 1982; Vernon and Ferguson 1969).

These studies have indicated that while fatigue and sleepiness occur in humans following exposure to concentrations above 100 ppm for 2 hours, no deterioration in performance or manual dexterity occurs following exposure to

levels up to 300 ppm. In one study, adverse effects on performance were seen

at 1,000 ppm, but no significant effects were seen at lower concentrations

(Kylin et al. 1967). In a frequently cited study, detrimental effects of 8 hours

exposure to 110 ppm TCE on performing tests of perception, complex reaction time, memory, and manual dexterity were found (Salvini et al. 1971).

Others have been unable to replicate this study (Stewart et al. 1970; Vernon

and Ferguson 1969). In a study where subjects were exposed to 1,000 ppm

TCE and optokinetic nystagmus measured, minimal effects were seen and

found to persist for only up to 2 hours (Kylin et al. 1967). Somewhat increased effects are seen when ethanol ingestion is added to the TCE exposure

(Ferguson and Vernon 1970; Winneke 1982), and it has been demonstrated

that ethanol will inhibit metabolism of TCE to its breakdown products,

trichloroethanol and trichloroacetic acid, thereby increasing TCE concentration in blood (Muller et al. 1975). In general, however, these studies have

shown that the behavioral effects of ethanol are more pronounced than TCE.

In summary, there is no compelling evidence that exposure to TCE at or

below 300 ppm has an adverse neurobehavioral effect.

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Methylene chloride (dichloromethane). Methylene chloride is widely used in industry for paint stripping, as a blowing agent for foam, as solvent for

degreasing, in the manufacture of photographic film, as the carrier in rapiddry paints, and in aerosol propellants. It is also used in the diphasic treatment

of metal surfaces, in the textile and plastics industry, and for extracting heatsensitive edible fats and essential oils. It is estimated that almost 100,000 individuals are exposed to methylene chloride in the workplace alone.

As with other solvents, methylene chloride has CNS depressant properties at

high levels of exposure and may lead rapidly to unconsciousness and death

(Moskowitz and Shapiro 1952; Winek et al. 1981; Tariot 1983; Sturmann et al.

1985; Horowitz 1986). This has been reported both in industrial settings

(Moskowitz and Shapiro 1952; Tariot 1983) and as a result of solvent inhalation abuse (Sturmann et al. 1985; Horowitz 1986).

Methylene chloride has generally been considered safer than other chlorinated hydrocarbons and has not attracted the attention it deserves as a possible cause of chronic CNS dysfunction. Methylene chloride is metabolized to

carbon monoxide (Stewart and Fisher 1972; Kubic et al. 1974; Ratney et al.

1974; Astrand et al. 1975) and therefore both its hypoxia effect as well as its

narcotic actions must be considered regarding methylene chloride’s CNS-depressant effects. Carbon monoxide, at high levels, and other forms of cerebral

hypoxia are known to cause permanent neurological sequelae.

The acute effects of exposure to methylene chloride have been studied in controlled experiments in humans (Stewart et al. 1972; Gamberale et al. 1975;

Winneke 1981). In one study, 11 healthy nonsmokers were exposed to levels

of methylene chloride up to 1,000 ppm for 1 to 2 hours (Stewart et al. 1972).

Inhalation of methylene chloride at 500-1,000 ppm for this length of time was

followed promptly by a sustained (at 24 hours post-exposure) elevation of

carboxyhemoglobin. These levels, however, never reached above 10 percent

saturation. Visual evoked responses in the three subjects tested showed an

increase in peak to peak amplitudes after 2 hours of exposure and returned to

baseline 1 hour after termination of exposure. No untoward subjective symptoms occurred at levels of exposure below 1,000 ppm. At exposure to concentrations of 1,000 ppm, two of three subjects reported mild light headedness,

which promptly resolved after cessation of exposure.

The effects of methylene chloride exposure on three tests of cognitive function (reaction time, short-term memory, calculation ability) were tested in 14

136
normal subjects (Gamberale et al. 1975). Repeated tests at exposures to 870,

1,740, 2,600, and 3,470 mg/m3 methylene chloride showed no statistically significant impairment in performance of these tests, although at the highest exposure levels, a greater variation in the responses was obtained for reaction

time than under control conditions.

Controlled exposure of normal volunteers for up to 24 hours to various concentrations (up to 800 ppm) of methylene chloride in five separate studies

showed the following abnormalities: After 2.5 hours of exposure to 500 ppm,

complaints of general uneasiness were noted. After 4 hours of exposure to

300 and 800 ppm mood rating scales were noted to be significant for depression in only one experiment. There was no impairment of cognitive performance as measured by tests of short-term memory and calculation ability in

any of these studies after 2.5 hours of exposure to methylene chloride at levels

up to 1,000 ppm. Some impairment was noted in psychomotor performance

and vigilance after 3 to 4 hours of exposure to 800 ppm.

Overall, studies of controlled human exposure to methylene chloride do not

show effects of central nervous system toxicity, except at higher levels of exposure, and even then, the effects are minimal and rapidly reversible. The one

exception may be in those inhalant abusers described where methylene chloride is a major component of the compound that they are abusing (Hormes et

al. 1986; Rosenberg et al. 1988a,b).

There have been few attempts to address the issue of chronic exposure and

permanent neurological sequelae to methylene chloride. A group of 46 men

working in a factory making acetate film reported an excess of neurological

symptoms when compared to a nonexposed referent group (Cherry et al.

1981). These individuals were exposed to a methylene chloride:methanol

(9:1) mixture, and methylene chloride concentrations were below 100 ppm.

Although neurological symptoms were increased in the exposed group, no

abnormalities were detected on neuropsychological tests. No evidence was

found of long-term damage that could be attributed to exposure to methylene

chloride. In a larger study to assess the potential chronic health effects of

methylene chloride, no increase in the number of expected deaths due to diseases of the nervous system were seen among 1,013 workers chronically

exposed to methylene chloride (Hearne et al. 1987).

In summary, the evidence suggests that methylene chloride does not produce

permanent neurological sequelae except with massive acute exposures that

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are associated with hypoxic encephalopathy. No evidence exists that chronic

low-level exposure causes any long-term CNS injury.

1, 1, 1-trichloroethane. 1, 1, 1- trichloroethane is widely used as an industrial

degreasing solvent and is relatively less toxic than other solvents, although

several reports of severe toxicity and deaths exist in the literature (Jones and

Winter 1983; Silverstein 1983; McCarthy and Jones 1983; Gresham and Treip

1983). Its acute toxicity has made it unsuitable as a volatile anesthetic, and its

use as a carrier in aerosols was abandoned in the United States in 1973.

In those cases in which post-mortem examination of the brain was undertaken, the pathologic changes suggested cerebral hypoxia related either to a

primary CNS depressant effect (Jones and Winter 1983), or secondary to cardiac or respiratory arrest (Jones and Winter 1983; Gresham and Treip 1983).

The possible mechanisms of the effects of 1, 1, 1-trichloroethane have been

postulated to be related either to its effect on the autonomic nervous system

(Kobayashi et al. 1987) or central sleep apnea (Wise 1983). Chronic cardiac

toxicity and possible sensitization to other inhalation anesthetics has also

been suggested as a possible mechanism of 1, 1, 1-trichloroethane toxicity

(McLeod et al. 1987).

There are several reports of the acute behavioral and neuropsychological

changes after voluntary exposure of humans to 1, 1, 1-trichloroethane

(Stewart et al. 1969; Salvini et al. 1971b; Gamberale and Hultengren 1973;

Mackay et al. 1987). There was no impairment on a series of psychomotor

tests following several days of exposure to 500 ppm of 1, 1, 1-trichloroethane

(Stewart et al. 1969). In another study, no behavioral effects were seen after

two 4.5 hour exposures to 450 ppm of 1, 1, 1-trichloroethane (Salvini et al.

1971b). Two studies demonstrated some performance deficits (Gamberale

and Hultengren 1973; Mackay et al. 1987). In one study, after 3.5 hours of exposure to 0, 175, and 350 ppm of 1, 1, 1-trichloroethane, abnormalities were

seen on some behavioral tests, most notably those tests concerned with attention and concentration and those concerned with analysis of grammatical

statements (Mackay et al. 1987). Overall, these studies suggest mild if any

acute effects of exposure of individuals to levels of trichloroethane up to 500

ppm.

With regard to low-level, chronic exposure to 1, 1, 1-trichloroethane, a clinical, neurophysiological, and behavioral study of female workers chronically

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exposed to this agent at levels of 110 to 990 ppm found no differences when

compared to a reference solvent-unexposed group (Maroni et al. 1977).

It appears that 1, 1, 1-trichloroethane is not associated with either acute or

chronic neurotoxicity at levels below 990 ppm, and that the only permanent

neurological sequelae are related to cerebral hypoxia after massive exposure.

In contrast to trichloroethylene, equivalent doses of trichloroethane do not

produce hearing loss when administered to rats (Pryor, this volume).

Gasoline. Gasoline is a complex mixture of organic solvents and other chemicals and metals. The sniffing of gasoline is common among various solvent

abusers, especially on some remote Native American reservations. Although

some CNS or peripheral neuropathies may occur due to the solvents in gasoline, other toxicities may result from the tetraethyllead (or its metabolite

triethyllead) (Coodin et al. 1980; Remington and Hoffman 1984; Goldings

and Stewart 1982; Prockop and Karampelas 1981; Eastwell 1985; Valpey et al.

1978; Robinson 1978; Hansen and Sharp 1978). In all cases in which high

lead levels are observed, hallucinations and disorientation, dysarthria, chorea,

and convulsions have been reported. The symptoms also have included moderate to severe ataxia, insomnia, anorexia, slowed peripheral nerve conduction, limb tremors, dysmetria, and sometimes limb paralysis. In most cases

the EEG is normal but in severe states, an abnormal to severely depressed

cortical EEG is observed. Only in one lethal case was there any kidney damage noted; electrolytes are usually in the normal range. Because many of

these symptoms in the early stages of the disease can be reversed by chelation

therapy with EDTA, BAI, and/or penicillamine, it is important to check the

serum lead levels in any chronic inhalant abuser to see if this treatment

should be prescribed.

Alcohols and solvents. One interesting phenomenon has been observed following the exposure to two or more solvents. Degreaser’s flush was ascribed

to a flushing of the face when occupational workers left their degreasing vats

and drank alcohol after leaving work (Pardys and Brotman 1974; Stewart et al.

1974). Also heavy drinking has been associated with toluene exposure (AnttiPoika et al. 1985. More recently, both humans and rats have been noted to be

thirsty when exposed to toluene and alcohol (Kira et al. 1988; Pryor et al.

1985). Also, animal studies have shown that solvents alter the metabolism of

alcohol and prolong its action (Takahashi et al. 1987; Cunningham et al.

1989). This might explain the “flushing phenomenon” but may or may not

139
relate to the psychological dependence on solvents or to the development of

thirst. An attempt to study the acute effects of alcohol and toluene, at low exposures in human volunteers, failed to produce any interaction by their

behavioral measures. This may be indicative that the interaction takes some

time and/or high levels of exposure to develop.

A recent report (McCormick 1990) identifies methanol intoxication as a

problem in an individual intoxicated on a spray can of carburetor cleaner containing toluene (42 percent), methanol (23 percent), and methylene chloride

(20 percent). Although mild acidosis did occur, the main concern was the

high blood level of methanol. Ethanol therapy was utilized to prevent formation of high levels of formic acid. The above mixture is common (very similar

in composition to paint thinner) and available to and used by solvent abusers;

yet the repercussions of prolonged use are unclear.

Nitrous oxide. Although nitrous oxide is not an organic solvent, it is discussed

here because of its potential for abuse. Nitrous oxide is a commonly used

anesthetic and has been noted for some unusual toxicities. This substance is

not usually thought of when one discusses inhalants, as it is unique both

chemically and in its physiological action. Although it is abused by youthful

experimenters, it is also abused by medical personnel. This substance, nitrous

oxide (N2O), is used as an anesthetic and as a propellant primarily for

whipped cream. “Laughing gas,” as it is euphemistically called, was abused

soon after it was discovered in the late 18th century. More recently it was

shown that central and peripheral nerve damage resulted following high levels

of N2O exposure, even in the presence of adequate oxygen (Layzer 1978).

The symptoms include numbness and weakness in the limbs, loss of dexterity,

sensory loss, and loss of balance. The neurological examination indicates

sensorimotor polyneuropathy. There is also a combined degeneration of the

posterior and lateral columns of the cord that resembles B12 deficiencies

(Layzer 1978). Studies focusing on the mechanism of action indicate that

cobalamins (vitamin B12) are inactivated by N2O; more recent studies have

focused on the methionine synthase enzyme which needs vitamin B12 to function (Nunn 1987). Although vitamin B12 (or folinic acid) does not aid recovery from this disease (Chanarin 1980; Nunn 1987), dietary methionine might.

Rehabilitation proceeds with abstinence and is relative to the extent of neurological damage. Recent reviews cover many of the medical aspects of the

adverse effects of and the pros and cons of using nitrous oxide (Brodsky and

Cohen 1986; Nunn 1987). Despite the widespread distribution of this

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information to the medical community and the reduced availability of pressurized cylinders, cases are still being observed (Schwartz and Calihan 1984).

In regard to dependency, animal studies on selectively bred mice for alcohol

dependence showed a cross-dependency on nitrous oxide (Belknap et al.

1987). Belknap and colleagues also observed handling-induced convulsions

shortly after cessation of nitrous oxide, which could be prevented by either

alcohol or nitrous oxide. This might indicate a physical dependence on

nitrous oxide that needs to be dealt with in treatment of this drug abuse state.

Nonnervous System Toxicity of Inhalant Abuse

Most of the adverse clinical effects of inhalant abuse are on the nervous system. There are however, other significant adverse effects on other organ systems, including the kidney, liver, lung, heart and blood.

Renal Toxicity. Inhalant abuse has also resulted in the hospitalization of indiviuals for various kidney disorders (Streicher et al., 1981; Will and McLaren

1981; Davidman and Schmitz 1988, Lavoie et al. 1987; Patel and Benjamin

1986; Baerg and Kimberg 1970; Bennett and Forman 1980; Ravnskov 1978;

Daniell et al. 1988; Jone and Wu 1988; Sarmiento Martinez et al. 1989;

Marjot and McLeod 1989; Mizutani et al. 1989; Nelson et al. 1990; Taverner

et al. 1988). One of the primary conditions leading to hospitalization has

been such severe rhabdomyolysis that some subjects are nearly paralyzed.

These subjects often have associated gastrointestinal (GI) involvement, including nausea, vomiting, and severe abdominal cramps. Lauwerys et al. 1985

have recently reviewed the reports on nephrotoxicity in humans.

In one of the early reports, Streicher et al. (1981) examined several cases and

described them in detail. Distal renal tubular acidosis occurred in groups of

paint and/or glue sniffers from the Southwest and Hawaii. They and others

have noted the recurrence of renal dysfunction associated with solvent abuse;

the disease state reappears in many individuals who return to their habit after

release from the hospital. They develop hyperchloremic metabolic acidosis,

hypokalemia, hypocalcemia, and other electrolyte imbalances. Solvents usually cause a unique distal type tubular acidosis, but proximal tubules may also

be affected.

A slightly different kidney dysfunction, glomerulonephritis, has also been

identified in workers using solvents (Harrison et al. 1986). This has been

noted in painters (Ravnskov 1978) and has been recently reviewed (Daniell et

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al. 1988). In addition, an interstitial nephritis leading to renal failure has

been recently reported (Taverner et al. 1988). Although toluene is often proposed as the toxic agent and is present in most of the substances abused by

these subjects, there have been no animal data to verify that toluene is the

primary agent or even one of a group of substances that can cause renal

dysfunction.

There are also reports that halohydrocarbons—chloroform and others (Lock

1989); methylene chloride (Rioux and Myers 1988); trichloroethylene

(Kimbrough et al. 1985); methoxyflurane (Brown and Gandolfi 1987); and

dichloropropane (Pozzi et al. 1985)—may contribute to, if not cause renal

damage. The pathologic changes in the kidney include tubular necrosis and

calcification. The reversibility of these changes is unknown and is likely dependent on the extent of the damage. Others (Keogh et al. 1984; Nathan and

Toseland 1979) observed signs of Goodpasture’s syndrome. Animal studies

have identified the nature of some of these nephrotic changes (Lock 1989;

Kimbrough et al. 1985). Animal studies have also shown mild nephrotic

changes following exposure to hydrocarbons (Short et al. 1987). In most cases

more than one substance is present; this may indicate that the most severe

nephrotic changes occur in the presence of two or more of these substances.

Thus several kinds of solvent mixtures are associated with either glomerulonephritis, distal renal tubular acidosis, or other nephrotic changes. Usually,

these different kidney disorders do not occur in the same individual.

Although metallic spray paints are frequently used by these subjects, they also

use paint thinners and glues. It would appear reasonable to conclude that

toluene may account for some but not all of these renal abnormalities, which

are likely due to a combination of toxicants in these toluene products—possibly including the metals contained in the spray paint such as cadmium and lead, which are known to be nephrotoxic (Wedeen 1984) or concurrent alcohol use (Jone and Wu 1988; Sarmiento-Martinez et al. 1989)

and/or infections (Ravnskov 1978; Yamaguchi et al. 1985; Farrell et al. 1985).

As more cases of renal toxicity are being reported, it is important that individuals exposed to high doses of solvents be checked for renal changes and

metabolic imbalance.

For most of these subjects, correction of the electrolyte disturbance and

proper fluid management usually restores the proper renal function and

eliminates the rhabdomyolysis, even in the more severely affected patients,

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within a few days. Caution about the use of bicarbonate early in the treatment

of these subjects has been discussed by Lavoie et al. 1987. Correction of salt

and electrolyte imbalance, including potassium, calcium, magnesium, and

chloride, should be considered in the treatment of solvent abusers for muscle

fatigue even in the absence of more severe kidney disorders.

Renal toxicity in pregnancy. One report emphasizes the need to be especially

alert for solvent abuse in pregnant women in regard to nephrotoxicity.

Goodwin (1988) reported live cases of renal tubular acidosis in pregnant

women. Although these mothers responded to treatment for their metabolic

imbalance after 72 hours and abstinence of solvent abuse, other individuals

may prove more difficult to treat for this metabolic disturbance.

Hepatotoxicity. Chlorohydrocarbons (e.g., trichloroethylene, chloroform,

halothane) have been known for years to produce hepato-toxicities (Baerg

and Kimberg 1970; Clearfield 1970; Dossing 1986; Hutchens and Kung 1985;

Farrell et al. 1985; Cordes et al. 1988; McCunney 1988; Hodgson et al. 1989;

Brown and Gandolfi 1987; Benjamin et al. 1985). Any individual who is

chronically exposed to these compounds would expect to develop hepato-renal toxicities depending on the dose and length of exposure (Benjamin et al.

1985). Buring et al. (1985) evaluated the effects of low levels of exposure measured retrospectively by several investigators. They concluded there is increased risk for operating room personnel where these chlorohydrocarbon

anesthetics are used. However, Brown and Gandolfi (1987) have questioned

whether liver toxicity occurs very often after use of halothane as an anesthetic.

Shaw et al. (1989) review these rare occurrences and their etiological factors.

In addition, the situations in which halothane hepatitis occurs has been reviewed by Neuberger and Davis (1983), who have proposed a hypoxic model

to explain those occurrences of hepatitis.

The recent increase in the inhalation of typewriter correction fluids that contain trichloroethylene and tri-, tetrachloroethanes increases the likelihood of

observing more of these toxicities in inhalant abusers (Greer 1984). This disease state is exemplified in two recent reports of apparent occupational

(poorly ventilated areas) overexposure. Nephronecrosis and/or hepatotoxicity

were observed after exposure to mixtures containing methylene chloride and

other solvents (Miller et al. 1985; Mizutani et al. 1988; Cordes et al. 1988) and

trichloroethane (Keogh et al. 1984; Hodgson et al. 1989). Methylene chloride

has been considered not to be hepatotoxic (Rioux and Myers 1988).

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However, a recent report may have identified an upper limit that may occur in

inhalant abuse (Cordes et al. 1988) where hepatotoxicity does occur.

Ketones, including acetone, potentiate halocarbon hepatotoxicity (Plaa 1988).

So far there have been few inhalant abusers noted to have irreversible liver

damage. For example, subjects with altered liver function, as noted by elevated serum liver enzymes, have recovered in a few weeks (Fornazzari et al.

unpublished). The low incidence of liver damage so far noted for this group

may be due to a low rate of use of chlorinated solvents. However, the frequent heavy use of alcohol concurrently with inhalants should be of concern

for this group, especially as they become older and will have used these substances for many years. When these patterns of “drug” exposure are known, it

would be advisable to conduct liver function tests.

Hepatocellular and other carcinomas are observed at high doses of

trichloroethylene (Kimbrough et al. 1985) and halothane (Redfern 1990).

Anesthetic chlorinated hydrocarbons (halothane, trichloroethylene, chloroform) are also considered to be carcinogenic (Cohen 1979).

Cardiotoxicity. Many solvent abusers may die from direct or indirect cardiotoxic actions of solvents without note of any public or private record.

More specifically, several recent reports have identified ventricular fibrillation

and cardiac arrest in hospitalized patients (McLeod et al. 1987; Cunningham

et al. 1987; Wiseman and Banim 1987; Boon 1987; Wright and Strobl 1984;

Ong et al. 1988, Wodka and Jeong 1989). Some of the subjects had inhaled

trichloroethylene (Mee and Wright 1980) or trichloroethane containing solvents (Wodka and Jeong 1989; McLeod et al. 1987) and some were additionally compromised by anesthesia (halothane—McLeod et al. 1987).

Fluorocarbons have been shown to cause arrythmias in animals (Taylor and

Harris 1970). Chenoweth and colleagues have shown that butane, hexane,

heptanes, gasoline, some anesthetics, and toluene also produce these arrythmias (Chenoweth 1977).

More recently, two reports (Cunningham et al. 1987; Wiseman and Banim

1987) have linked glue sniffing to arrythmias and dilated cardiomyopathy.

However, the linkage of arrythmia to glue sniffing is not well supported by

animal studies. Glues usually do not contain halocarbons but do contain

toluene and other hydrocarbons. The somewhat different cardiotoxicities

noted above are not all easily explained, but congenital or other environmental causes were not ruled out. When observed, antiarrythmic therapy should

144
be used (McLeod et al. 1987). Exercise and adrenaline exacerbate these cardiotoxicities, and efforts to minimize these situations should therefore be instituted. Also, anesthesia should not be induced in patients shortly after

intoxication, and one should probably avoid the use of halogenated hydrocarbons in other circumstances where heavy solvent exposure is suspected.

Hematologic toxicity. There are three areas of concern in regard to solvent

inhalation and the hematopoietic system. Two of these relate to blood

dyscrasias as the result of the abuse of solvents. Methylene chloride exposure

can increase the carboxyhemoglobin levels (Horowitz 1986), a change that

also occurs with cigarette smoking. The levels of carboxyhemoglobin may become sufficiently high to cause brain damage (Barrowcliff and Knell 1979) or

death (Manno et al. 1989). A second group of substances, the organic nitrites,

produces methemoglobinemia and hemolytic anemia (Wason et al. 1980,

Brandes et al. 1989). A third substance, benzene, has been identified as causing aplastic anemia and acute myelocytic leukemia (Lauwerys et al. 1985,

Austin et al. 1988). Benzene is present in thinners, varnish removers, and

other solvents and in varying proportions in gasoline.

Nitrite intoxication. One group of substances, the volatile liquid “amyl” and

“butyl” nitrites, deserve special discussion. During the late 19th and early 20th

centuries amyl nitrite was used in clinical practice as a vasodilator to treat

angina pectoris. Although this use of the drug is uncommon today, it is used

for diagnostic purposes in echocardiogram examinations (Rosoff and Cohen

1986) and for cyanide poisoning (Klimmek and Krettek 1988). These drugs

are not the typical solvents previously described; however, they are often

included in the “inhalant abuse” category. As with nitrous oxide, some individuals abuse isoamyl (amyl) or isobutyl nitrites, and the propyl nitrites.

Homosexuals have been reported to use these substances for sphincter dilation and penile engorgement. Use by others for nonsexual purposes is unclear. A recent study could not correlate changes in regional blood flow with

any psychological measures or somatic changes (Mathew et al. 1989a). These

studies do not offer any explanation for why individuals become dependent on

nitrites. However, the finding by Mathew and colleagues that nitrites reduce

anger, fatigue, and depression may offer a clue.

The nitrites are not usually considered toxic during inhalation because of syncope (fainting). However, Guss et al. (1985) noted a dangerously high 37 percent methemoglobin level in a normal subject who had used isobutyl nitrite.

145
This methemoglobinemia is the major identified toxicity and is considered the

cause of several deaths (Wood and Cox 1981). There is a specific treatment

for nitrite overdose. The high and slowly reversible reduction of methemoglobin can be aided by the use of methylene blue (Smith et al. 1980).

Organic nitrites have also been reported to produce bradycardia (Rosoff and

Cohen 1986), reduce killer cell activity (Lotzova et al. 1984), produce allergic

reactions (Dax et al. 1989), and be potentially carcinogenic (Osterloh and

Goldfield, 1984). These latter effects are of special concern in the development of AIDS in that there is an association between the development of

Kaposi’s sarcoma and high amyl-butyl nitrite use (Newell et al. 1984;

Haverkos et al. 1985; Moss et al. 1987). The ability to produce nitrosamines

has fueled the speculation that nitrites are carcinogenic (Osterloh and

Goldfield, 1984; Mirvish and Haverkos 1987; Yamamoto et al. 1987). Yet, in

contrast to sodium nitrite, organic nitrites produce methemoglobin instantly

in vitro (Klimmek et al. 1988) and may therefore not be around long enough

to produce nitrosamines. Thus, the rapid oxidation of organic nitrites by

hemoglobin and the fact that detectable levels of organic nitrites in blood are

noted only briefly after administration (Osterloh and Goldfield 1985) call into

question this hypothesis. Also, organic nitrite effects only the isolated immune or bacterial cells (Dunkel et al. 1989) and in a nonspecific manner

(Lewis and Lynch 1988; Jacobs et al. 1983), and not the immune state of the

whole rodent. While mutagenicity appears possible under special conditions,

carcinogenicity is far from proven.

Neonatal syndrome. There is little direct information regarding a “fetal solvent

syndrome” or related teratogenic changes as a result of solvent exposure during pregnancy. However, authors of studies of infants of mothers who chronically abuse solvents (Hersh et al. 1985; Hersh 1989; Goodwin 1988) cite this

as a possibility. (Also note Tenenbein’s discussion of this issue in this volume.) Subjects in some of the above studies inhaled paint thinner and paint

sprays and drank various quantities of alcohol. Whether the toluene (stated

to be pure toluene in the “thinner”) and alcohol or other environmental factors are responsible is open to question. Toluene may augment the fetal alcohol syndrome such that a fetal alcohol syndrome occurs at lower than usual

levels of alcohol consumption. It is also worth noting that the mothers of the

infants in Hersh’s study showed ataxia, mild tremors, and slurred speech,

while the mothers in Goodwin’s study presented with severe renal tubular

acidosis. The concomitant influence of undernutrition, other substance

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abuse, or even genetic predisposition needs to be clarified through further

studies.

With so little knowledge, and yet with all the potential dangers, it is very important that pregnant women not be exposed to very high concentrations of

solvents. It is encouraging to know that a critical prospective study of workers

exposed to low levels of solvent showed no more abnormalities than the

carefully matched controls (Eskenazi et al. 1988). This does not, however,

diminish the need for the avoidance of exposure of pregnant women to moderate to high levels of solvent.

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Authors

Neil L. Rosenberg, M.D.

Center for Occupational Neurology

and Neurotoxicology

Colorado Neurological Institute

125 East Hampden Avenue

Englewood, CO 80150

Charles W. Sharp, Ph.D.

5600 Fishers Lane, Room 10A-31

National Institute on Drug Abuse

Rockville, MD 20857

171

Clinical/Biophysiologic Aspects

of Inhalant Abuse

Milton Tenenbein

While inhalant abuse is known to produce dysfunction and damage affecting

several of the body’s organ systems, Rosenberg and Sharp have appropriately

decided to focus upon the nervous system and have provided a comprehensive

review. My chapter will chiefly focus upon the methodologic barriers impeding research into the neurologic aspects of inhalant abuse and identify other

relative aspects of solvent toxicity. Especially, I will briefly discuss a clinical

aspect of inhalant abuse that is barely discussed in the literature, the teratogenic effects of this practice. Because there are many methodological barriers, I have chosen to conclude somewhat provocatively by suggesting a need to

prioritize inhalant abuse research by proposing that research into causation,

prevention, and rehabilitation be emphasized.

Investigating the Neurotoxicity of Inhalant Abuse

Neurotoxicity as an outcome of volatile solvent abuse is predictable. In order

for a product to be favored as an agent for inhalant abuse, it must rapidly enter the central nervous system in quantities high enough to produce the desired effect: a pleasurable change in affect. Therefore, some alteration of central nervous system function, or perhaps even structure, must be occurring.

Since the affective change is transitory, it is expected that this associated functional or structural alteration is reversible. However, it is reasonable to assume that at some point after chronic exposures, irreversible changes may occur. A stronger case for this speculation is made when one considers that a

173
major use of these chemicals is to dissolve various nonpolar organic substances. The central nervous system is richly endowed with organic lipids;

thus, from an overly simplistic perspective, there is the potential for portions

of the brain to be dissolved away over time.

Traditionally, the pathophysiology of a condition is studied and characterized

in order to devise effective treatments and perhaps even a cure. If the condition is known to be produced by a drug or a chemical, then the investigation

would include a study of the pharmacokinetics and pharmacodynamics of the

agent of concern. The former describes the rates of absorption, distribution,

metabolism, and excretion of the compounds in question, while the latter

deals more with the interrelationships of these states and with dose-effect relationships. Both require knowledge of the actual dose of the drug or chemical and accurate methods of measuring its concentration within the body.

Additionally, pharmacodynamics requires the measurement of the induced

effects.

There are several potential methods for measuring the effects of a drug or

chemical within the body. In general, these include clinical and functional assessments (often subclinical) and structural alterations. From the perspective

of the clinical and biophysiologic effects of inhalant abuse upon the human

nervous system, actual methods could include a neurologic medical history

and physical examination (clinical); various electrophysiologic and psychometric assessment modalities (functional); and advanced organ imaging techniques (structural). There is obvious overlap within this classification because

of the interrelationship between structure and function.

Assessment of the Pharmacologic Agent

Establishing the causative agent is the first priority, but for volatile solvent

abuse, this is problematic. Historically, toluene was one of the first chemicals

to be implicated (Grabski 1961) and several other convincing reports of

toluene-induced neurotoxicity have appeared (Boor and Hurtig 1977; Lazar et

al. 1983; Malm and Lying-Tunell 1980). These descriptive human examples,

especially when supported by strong controlled animal studies (Pryor et al.

1984), establish a cause-and-effect relationship between chronic toluene

abuse and neurotoxicity. This has led to considering it as the etiologic agent

whenever its presence is known, and at times just assumed, despite the presence of other potential neurotoxins. This has been commented upon else174
where (Cavanagh 1983). The gold standard for attributing neurotoxicity to

toluene in a chronic inhalant abusing patient is chemical analysis of all

inhalants abused by the individual in order to rule out other neurotoxins.

This is absent from most reports of neurotoxicity attributed to toluene

(Fornazzari et al. 1983; Kelly 1975; King 1982; Schikler et al. 1982).

While not attempting to minimize toluene as a neurotoxin, the attention paid

to it may give the impression, especially to the lay public, that the other

abused inhalants are less toxic or even nontoxic. This has resulted in specific

legislation against toluene-based products, which then further creates the

impression of relative safety of the “nonregulated” substances. Furthermore,

favored products vary from community to community and are not necessarily

toluene based in each or sometimes any area. In our catchment area we have

three distinct cohorts. In the inner city, toluene and halogenated aliphatic

hydrocarbon based products are chiefly utilized. In small settlements in a

remote area east of us, n-hexane based products are commonly abused

(Tenenbein et al. 1984), while in similar settlements to the north, gasoline is

favored (Boeckx et al. 1977). In the United Kingdom, butane is a popular

substance of inhalant abuse (Anderson et al. 1985), and this is currently

becoming prevalent in the United States. Propane is abused in the far

Canadian North and in remote areas of Australia. Significant morbidity and

mortality are not limited to toluene and also occur in these cohorts.

Thus there is a need to study other agents. Considering the virtually endless

number of chemicals involved in inhalant abuse, this becomes an impossible

task. However, a starting point would be examining some of the more common ones from each class. The goal of this endeavor would be the identification of safer agents that could then replace the more toxic ones currently in

consumer products.

The pharmacokinetics and pharmacodynamics of these abused substances at

doses that produce euphoria in humans are unknown and will almost certainly

remain so. Such data would be helpful in determining the doses and duration

of inhalant abuse required to produce chronic toxicity. This information

could also address the perplexing question as to why some individuals seem to

be more sensitive to the neurotoxic effects of chronic inhalant abuse through

the related discipline of pharmacogenetics. Some individuals metabolize

drugs and chemicals at different rates than the rest of the population (Vesell

1984).

175
Assessment of Effects

Clinical assessment includes medical history and physical examination. The

volatile solvent abuser cannot be considered as a reliable historian. Reasons

for inaccurate information regarding the types of abused products, the

amount abused over a period of time, and the frequency and duration of abuse

range from frank lack of recollection to fear of self-incrimination. Responses

to inquiries regarding potential acquired disabilities may be inaccurate

because of denial or lack of recognition. While physical examination is

straightforward, demonstrated abnormalities are only detectable late in the

clinical course. Furthermore they may not result from chronic solvent abuse

but relate to coexisting confounding variables such as the abuse of other substances and poor nutrition.

Two methodologies that have been used to assess subclinical functional

abnormalities are evoked potential and psychometric testing. There have

been many anecdotal reports of abnormal evoked potentials in patients with

frank central nervous system damage. Of perhaps even greater interest are

the findings of abnormalities in brainstem auditory evoked potentials

(Rosenberg et al. 1988) and in visual evoked potentials (Cooper et al. 1985) in

apparently neurologically normal solvent abusers. This is supported by our

own data (Tenenbein and Pillay, in press). Auditory, visual, and

somatosensory evoked potentials were obtained from 15 neurologically

normal solvent abusing children. This cohort abused a wide variety of

products, and abnormalities were found in just over one half of them. Thus

evoked potential testing may be an objective marker of early neurologic

damage with potential usefulness for counseling and intervention. While this

appears to be a promising tool, considerable work is required to determine if

it can fulfill this goal.

Much has been written regarding psychometric evaluation of solvent abusers,

and this topic has been reviewed elsewhere (Ron 1986). Some shortcomings

of the published research utilizing this method of investigation are that it is

frequently uncontrolled; there is often a lack of differentiation between acute

and chronic effects, there are concerns about the many tests used, and there

are concerns regarding the validity of these tests and the lack of normative

data for specific ethnocultural groups under study. These issues, along with

confounders frequently present in solvent abusers, such as preexisting psy176
chologic morbidity and the effects of other substances of abuse have not surprisingly led to confusing and conflicting results.

Structural central nervous system abnormalities are now simply and noninvasively assessed by modern diagnostic imaging techniques. Abnormalities in

both computerized tomography (Fornazzari et al. 1983) and magnetic resonance imaging (Rosenberg et al. 1988) have been demonstrated in solvent

abusers who were overtly neurologically abnormal. While the limitations of

the latter techniques have not been fully characterized, these modalities

would seem to be relatively insensitive for subclinical abnormalities, and their

expense is a further limiting factor.

Teratogenic Effects of Inhalant Abuse

The effects of inhalant abuse upon the unborn child are unknown. Since

chronic abuse produces functional and structural damage in the mature individual, it is reasonable to expect that the developing fetus would be at particular risk. Dysmorphic features, as well as physical and neurologic impairments have been reported (Hersh et al. 1985; Hersh 1989; Hunter et al. 1979).

Anecdotal unpublished personal observations include acute neonatal withdrawal, transient neonatal renal tubular acidosis, intrauterine growth retardation, developmental delay, and impairments of vision and hearing. Much

more information is needed to characterize the consequences of solvent abuse

during pregnancy in order to devise effective strategies for dealing with this

problem.

Clinical Effects of Inhalant Abuse: Future Research

There are many barriers for research into this problem. There are too many

chemicals and mixtures to consider. We lack the tools to reliably measure the

early subclinical effects. Controlled human volunteer studies cannot be done;

therefore, research will likely remain descriptive in nature—largely descriptions of individual cases and small groups of individuals. Case controlled

studies provide a more powerful methodology; however, when dealing with

solvent abuse, the matching of appropriate controls is particularly problematic because it is virtually impossible to verify that an individual has not

abused volatile solvents.

177
Since inhalant abuse has its beginnings in childhood, the ethical issues of

research on children compound this problem. Prospective studies are not

possible because of the need to intervene when this practice is discovered.

Retrospective studies are flawed by incomplete and inaccurate data. In the

case of volatile solvent abuse, key information that is often of questionable

accuracy includes the identity of the abused substances, and the dose, frequency, and duration of abuse.

One could take the position that research directed toward identifying specific

pathophysiology of volatile solvent abuse induced neurotoxicity is unlikely to

achieve its goal. But, perhaps this may not be so unfortunate, because the

likelihood of finding a specific treatment or cure for neurologic damage,

whatever its etiology, is not great. Efforts may be better directed toward the

early identification of those individuals at particular risk for permanent damage. A simple, noninvasive, and inexpensive screening test would be ideal. In

this way, those in need of intervention could be identified prior to the onset of

irreversible damage. It would seem that more would be gained from a better

understanding of risk factors in order to formulate preventive strategies, and

that the inhalant abuser would be better served if we gained more insight into

appropriate rehabilitative strategies prior to the onset of neurologic damage.

References

Anderson, H.R.; MacNair, R.S.; and Ramsey, J.D. Deaths from abuse of

volatile substances: A national epidemiological study. Br Med J 290:304-

307, 1985.

Boeckx, R.L.; Postl, B.; and Coodin F.J. Gasoline sniffing and tetraethyl lead

poisoning in children. Pediatrics 60:140-145, 1977.

Boor, J.W., and Hurtig H.I. Persistent cerebellar ataxia after exposure to

toluene. Ann Neurol 2:440-442, 1977.

Cavanagh, J.B. Progressive optic atrophy and sensorineural hearing loss due

to chronic glue sniffing. J Neurol Neurosurg Psychiat 46:966, 1983.

Cooper, R.; Newton P.; and Reed M. Neurophysiological signs of brain damage due to glue sniffing. Electroenceph Clin Neurophysiol 60:23-26, 1985.

178
Fornazzari, L.; Wilkinson, D.A.; Kapur, B.M.; and Carlen, P.L. Cerebellar,

cortical and functional impairment in toluene abusers. Acta Neurol

Scand 67:319-329, 1983.

Grabski, D.A. Toluene sniffing producing cerebellar degeneration. Am J

Psychiat 118:461-462, 1961.

Hersh, J.H. Toluene embryopathy: Two new cases. J Med Genet 26(5):333-

337, May 1989.

Hersh, J.H.; Podruch, P.E.; Rogers G.; and Weisskopf, B. Toluene

embryopathy. J Pediatr 106:922-927, 1985.

Hunter, A.G.W.; Thompson, D.; and Evans, J.A. Is there a fetal gasoline

syndrome? Teratology 20:75-80, 1979.

Kelly, T.W. Prolonged cerebellar dysfunction associated with paint-sniffing.

Pediatrics 56:605-606, 1975.

King, M.D. Neurological sequelae of toluene abuse. Human Toxicol 1:281-

287, 1982.

Lazar, R.B.; Ho, S.U.; Melen, O.; and Daghestani, A.N. Multifocal central

nervous system damage caused by toluene abuse. Neurology 33:1337-

1340, 1983.

Malm, G., and Lying-Tunell, U. Cerebellar dysfunction related to toluene

sniffing. Acta Neurol Scand 62:188-190, 1980.

Pryor, G.T.; Rebert, C.S.; Diekinson, J.; and Feeney, E.M. Factors affecting

toluene-induced ototoxicity in rats. Neurobehav Toxicol Teratol 6:223-

238, 1984.

Ron, M.A. Volatile substance abuse: A review of possible long-term neurological, intellectual and psychiatric sequelae. Br J Pychiat 148:235-246,

1986.

Rosenberg, N.L.; Spitz, M.C.; Filley, C.M.; Davis, K.A.; and Schaumburg,

H.H. Central nervous system effects of chronic toluene abuse—Clinical,

brainstem evoked response and magnetic resonance imaging studies.

Neurotoxicol Teratol 10:489-495, 1988.

179
Schikler, K.N.; Seitz, K.,; Rice, J.F.; and Strader, T. Solvent abuse associated

cortical atrophy. J Adolescent Health Care 3:37-39, 1982.

Tenenbein, M.; deGroot, W.; and Rajani, K.R. Peripheral neuropathy following intentional inhalation of naphtha fumes. Canad Med Assoc J

131:1077-1079, 1984.

Tenenbein, M. and Pillay, N. Sensory evoked potentials in inhalant (volatile

solvent) abuse. J Paediatr Child Health, in press.

Vesell, E.S. Pharmacogenetic perspectives: Genes, drugs and disease.

Hepatology 4:959-965, 1984.

Author

Milton Tenenbein, M.D., FRCPC, FAAP, FAACT

Professor of Pediatrics, Pharmacology, and Medicine

and Community Health Sciences

University of Manitoba

and

Children’s Hospital

840 Sherbrook Street

Winnipeg, Manitoba, Canada R3A 1S1

180
Death Among Inhalant Abusers

James C. Garriott

Inhalant abuse is a significant problem among youth in the Southwestern

United States. A number of studies have addressed the potential adverse

effects of the practice to include psychological and medical effects (Bass 1970;

Hayden et al 1977; Comstock and Comstock 1977; Bruckner and Peterson

1977; Prockop and Couri 1977; Korman 1977; Korman et al. 1978; Boeckx

and Cooding 1978; De La Garza 1978). In the late 1960s and early 1970s,

sudden death among inhalant abusers was frequently observed (Bass 1970;

Garriott and Petty 1980) and was found to be primarily related to the use of

fluorocarbons and a few solvents that were found to induce cardiac arrythmias

(Aviado 1977). After the prohibition of the use of fluorocarbons in aerosol

spray products, these agents became more difficult to obtain, and deaths

among teenagers from this source greatly diminished (Garriott and Petty

1980).

The practice of inhalant abuse has not ceased, however, and the preferred

agents in south Texas have become primarily spray paints, lacquers, or other

toluene-containing products, which are readily available to the public.

This chapter follows from an investigation of all deaths occurring in Bexar

County, Texas, between 1982 and 1988 in which recent inhalant abuse by the

decedent could be ascertained. Prior studies of inhalant-involved deaths have

focused on deaths believed to have resulted directly from inhalant abuse. This

was the focus of an early study carried out in the 1970s in Dallas County,

Texas in which 35 deaths were found to be directly caused by inhalants

(primarily fluorocarbons) (Garriott and Petty 1980). In contrast, only 18 per181
cent of the deaths in the current study were directly attributable to inhalant

abuse. Although few deaths were found to be due to inhalant toxicity, many

inhalant users met with a violent death, possibly related to but not directly

caused by these volatile substances. Suicide and homicide were the most

prevalent means of death in inhalant abusers, and the predominant method of

suicide was hanging. This new analysis demonstrates a potential association

between inhalant use and violent death and implies a new relationship to

suicide.

Most of the inhalant-related deceased were teenagers, with 21 (54 percent)

under 20 years of age (see table 1). It is interesting to note, however, that

nearly half were adults, demonstrating that inhalant abuse is not confined to

teens and adolescents. The average age was 19.3 years; the youngest was 8,

and the oldest was 32 years of age. Males outnumbered females 34:5. Also,

79 percent had Hispanic surnames but were classified as “white” by the medical examiner. (In Bexar County, it is estimated that 53 percent of the

population is of Hispanic origin.)

Table 1. Ages/sex of inhalant abusers

Age/sex No.

up to 13 2 (5%)

13-19 19 (49%)

20-29 16 (41%)

Over 30 2 (5%)

Total 39 (100%)

Males 34 (87%)

Females 5 (13%)

182
The inhalants identified in all cases are listed in table 2. As reflective of the

incidence of use in this community, the great majority (82 percent) had used

toluene-containing products; toluene was detected in their blood at autopsy.

The next most frequently used solvents were a combination of trichloroethylene plus 1,1,1-trichloroethane (10 percent), resulting from the use of typewriter correction fluids. The remaining abused substances included

dichlorodifluoromethane (Freon 12), gasoline, and nitrous oxide. If present

in sufficient amounts, the toxicological procedures would have also detected

alkane gases (e.g. butane), benzene, methylene chloride, and most anesthetic

gases (Foerster and Garriott 1981). In addition, conventional toxicological

tests determined the presence of most drugs and/or alcohol. Ethanol was

commonly observed and ranged from 0.07 to 0.28 g/dl in 49 percent of the

cases.

Table 2. Chemical agents measured at autopsy

Substances measured Possible products

Prevalence of

substances

Toluene Spray paints,

lacquers

32 (82%)

Trichloroethylene and

1,1,1-trichloroethane

Typewriter correction

fluids and solvents 4 (10%)

Dichlorodifluoromethane Refrigerants 1 (2.7%)

Gasoline Commercial gasoline 1 (2.7%)

Nitrous Oxide Nitrous Oxide tanks 1 (2.7%)

Total

Alcohol was also present in 19 (49%) of the cases.

39 (100.1%)1

1

Total does not equal 100 percent due to rounding.

183
Table 3. Elements of autopsied subjects

Manner of

death

Number

(%)

Products

used

Major

solvents

Other

drugs

Suicide:

Hanging

Gas (CO)

Accident:

Vehicle—

passenger

Pedestrian

Fall

Overdose

Train

Homicide:

Gunshot

Stabbing

Other

Accident:

Inhalant

Arrhythmia

Other

Undetermined

Total

11 (28)

10

1

10 (26)

1

3

2

3

1

9 (23)

4

3

2

7 (18)

4

3

2 (5)

39(100)

*Fluid = typewriter

and 1,1,1-trichloroethane

Spray paint Toluene

Toluene

Unknown

Spray paint

Fluid*

Unknown

Toluene

Toluene

Trichl*

Toluene

Toluene

Spray paint Toluene

Spray paint Toluene

Spray paint Toluene

Spray paint Toluene

Gasoline

Fluid*

Refrigerant

N2O tank

Gasoline

Trichl*

DichlorodiSpray paint

fluoromethane

N2O Ethanol

Toluene

Methylene

chloride

Toluene Ethanol

Ethanol

Ethanol

Heroin

Phenothiazine

Ethanol

Cannabis

Propoxyphene

Ethanol

Phenothiazine

Ethanol

Cannabis

Cocaine

Heroin

Ethanol

correction fluid; Trichl = trichloroethylene

184
Deaths Resulting From Inhalant Abuse

Among all cases where inhalants were suspected, there were 39 cases in which

solvents or gaseous inhalants were detected. In only seven cases (18 percent)

were the deaths considered to have been directly the result of inhalant toxicity

(table 3). Only one death was directly attributable to toluene exposure, probably from spray paint abuse. That product also contained methylene chloride,

a substance that could have contributed to the cause of death (arrhythmia).

Toluene has been implicated in a few deaths (Baselt and Cravey 1990); those

cases reported in the past may not all be attributable to toluene, as authors often did not critically rule out other substances. Toluene has been demonstrated to induce heart block at high concentrations in mice (Taylor and

Harris 1970), but human death from toluene abuse is quite rare. The mean

blood concentration in the 32 toluene cases reported here was 3.78 (±5.1)

mg/L. These concentrations do not appear to have been indicators of lethality

nor of any specific toxicity, as much higher concentrations of toluene have

been observed in the blood (greater than 30 mg/L) of inhalant abusers without any observable toxicity (Garriott et al. 1981).

Gasoline inhalation also has not been frequently reported to cause death, although in some studies, severe toxicity and death have been reported from the

accompanying lead poisoning (Boeckx and Cooding 1978, Poklis and Burkett

1977; Kurt et al. 1982). In this study, the death was believed to have resulted

from cardiac arrythmia due to gasoline inhalation.

Abuse of nitrous oxide also has caused deaths; the lethal mechanism here was

most likely anoxia (as is the case in most nitrous oxide related deaths), rather

than a direct toxic effect of nitrous oxide (DiMaio and Garriott 1978). This

gas can be inhaled in very high concentrations under controlled circumstances

without causing harm (Marshall and Wollman 1980).

Dichlorodifluoromethane (Freon 12) from a refrigerant regenerator was

directly responsible for one death due to cardiac arrhythmia (Aviado 1977).

The solvent combination found in typewriter correction fluid (e.g.,

trichloroethylene and 1, 1, 1-trichloroethane) was the next most frequently

detected inhalant after toluene. A much higher percentage of deaths was

attributed to toxicity from these solvents (2 of 4) than for toluene (1 of 32).

The lethal mechanism is considered to be cardiac arrythmia due to myocardial

sensitization, as described for the fluorocarbons (Aviado 1977).

185
Deaths Resulting From Suicide

The most prevalent manner of death in these inhalant abusers was suicide (28

percent) (table 3). The age range of these suicides was 12 to 32, with 7 of the

11 being teenagers. These were compared to a cohort of 38 suicides in noninhalant-abusing teenagers during the same period. In the latter group, only 7

of 38 (18 percent) died by hanging, while most (66 percent) died from gunshot

(see table 4). This contrasts with 91 percent of the inhalant abuse suicides

choosing hanging as the method of suicide.

Table 4. Type of suicides in noninhalant abusing teenagers

Gunshot 25 (66%)

Hanging 7 (18%)

Drug overdose 4 (11%)

Carbon monoxide 2 (5%)

Total 38 (100%)

Alcohol was present in 12 cases (32%)

Delta9-THC was present in 4 cases (10%).

Deaths Resulting From Accident and Homicide

Deaths resulting from accidents (26 percent) and homicides (23 percent) were

other major categories of violent deaths among inhalant abusers. These

tended to result from aberrant aggressiveness or bizarre accident-prone

behaviors (e.g., challenging auto or train traffic).

186
This analysis provides a new perspective of the consequences associated with

inhalant use, that is, an association with violent death and especially suicide.

Almost two thirds of these deaths resulted from nondrug related causes. The

majority of the individuals had used products containing the solvent, toluene,

as evidenced by its detection in bodily specimens at autopsy. This relationship

with violent death may be similar to that observed for alcohol, a central nervous system depressant that is also highly associated with violent death.

Effects such as general central nervous system depression, impaired thinking

and judgement, and slowed reaction times are common to both intoxicants.

Inhalants also have been associated with aggressive, especially self-aggressive,

behavior (Korman 1977), as with alcohol. The high proportion (28 percent)

of inhalant abusers committing suicide and the number of homicides (23 percent) may be related to that phenomenon. Suicide is a common outcome of

severe clinical depression, and chronic solvent abusers have been reported to

have higher rates of depression (Zur and Yule 1990). However, the high rate

of suicide by hanging (10 of 11 solvent abusers) is not explainable, especially

since less than 1 in 5 noninhalant abusing suicide victims chose this method

(table 4). Both the high incidence of suicides, as well as violent or bizarre behavior leading to violent death as occurred in some homicide and accident victims in this study, may be evidence of neuropathy and cerebral dysfunction in

chronic inhalant abusers, described in clinical studies (Comstock and

Comstock 1977; Filley et al. 1990; Rosenberg et al. 1988).

Future Research on Inhalants

Evaluation of Solvent Mixtures and Other Toxic Additives

Most research on inhalant abuse toxicity has focused on pure solvents and

select solvent mixtures. Although a wide variety of solvent-containing products are available, a large portion of solvent abuse involves only a few preferred products. Predominant are: (1) those that contain a high concentration of toluene with or without other solvents, (2) those that contain

trichloroethylene and/or 1,1,1-trichloroethane, and (3) less commonly used

agents such as alkyl nitrites, alkane gases (butane, propane), hydrocarbon

mixtures (e.g., gasoline, paint removers) and anesthetic gases (including

nitrous oxide).

187
Product formulators do not always provide the exact composition of the solvents on their products, and minor components, or even contaminants unknown to the manufacturer may be present and not recognized. Minor components can be extremely important, however, as exemplified by the relatively

small amounts of organic lead in leaded gasoline responsible for severe lead

encephalopathy in gasoline sniffers and the relatively low levels of hexane that

can induce polyneuropathy. Also, paint sniffers’ lung tissue at autopsy sometimes contains metal-containing pigments (Garriott and DiMaio unpublished). Since sniffers, rarely, if ever, use the pure solvent, one can not be sure

whether the neuropathies or other forms of toxicity are primarily due to the

solvent or to other substances in these abused products, or even to other

related substance abuse.

Research can be focused on those few substances most often occurring in

commonly abused products (toluene, trichloroethylene, 1,1,1-

trichloroethane), and combinations of these with or without alcohol—especially since alcohol is commonly ingested along with solvents.

Additionally, methylene chloride, another common solvent, as well as other

components uncovered in commonly abused products could be evaluated.

More comprehensive analyses of abused products should be performed, with

the goal of identifying known toxic agents, especially if and when unexplained

toxicity occurs following inhalant exposure.

Clinical Studies

Many physiologic systems are known or reported to be affected by inhalants

and can be evaluated by standard medical testing. The evaluation should

include screening for a broad range of toxic effects to include nervous system,

liver and kidney damage, effects on the blood-forming organs, respiratory system effects, and effects on the immune system.

Testing for neurological and behavioral effects should also be carried out, as

this form of toxicity may be the most serious and irreversible of all the potential toxic effects of solvents. To determine nonacute irreversible toxicity,

analyses must be done in a controlled fashion, using analytical techniques to

rule out recent use of inhalants. Toluene, for example, has an approximate

half-life of 72 hours in the body (Baselt and Cravey 1990), so some acute

effects may persist for a week or longer.

188
The role of other factors, such as noninhalant drug abuse and environmental

factors, should also be evaluated in any clinical studies. A recent study of previous inhalant abusers tested for drug abuse (other than alcohol and

inhalants) found that 81 percent were positive for one or more of the commonly abused (for nonmedical purposes) drug groups (Joe et al. 1991). These

tests can determine drug use within the past 1-5 days (depending on the drug).

Liver damage from other sources and poor nutrition may also contribute to

poor health of these subjects.

References

Aviado, D.M. Preclinical pharmacology and toxicology of halogenated solvents and propellants. In: Sharp, C.W., and Brehm, M.L., eds. Review of

Inhalants: Euphoria to Dysfunction. NIDA Research Monograph 15.

Rockville, MD: National Institute on Drug Abuse, 1977. pp. 164-184.

Baselt, R.C., and Cravey, R.H. Disposition of Toxic Drugs and Chemicals in

Man. 3rd ed. Littleton, MA: Year Book Medical Publishers, Inc., 1990. p.

82.

Bass, M. Sudden sniffing death. JAMA, 212:2075-2079, 1970.

Boeckx, R.L., and Cooding, F.U. An epidemic of gasoline sniffing. In: Sharp,

C.W., and Carroll, L.T., eds. Voluntary Inhalation of Industrial Solvents.

Rockville, MD: National Institute on Drug Abuse, 1978. pp. 137-158.

Bruckner, J.V., and Peterson, R.G. Toxicology of aliphatic and aromatic

hydrocarbons. In: Sharp, C.W., and Brehm, M.L., eds. Review of

Inhalants: Euphoria to Dysfunction. NIDA Research Monograph 15.

Rockville, MD: National Institute on Drug Abuse, 1977. pp. 124-163.

Comstock, E., and Comstock, B. Medical evaluation of inhalant abusers. In:

Sharp, C.W., and Brehm, M.L., eds. Review of Inhalants: Euphoria to

Dysfunction. NIDA Research Monograph 15. Rockville, MD: National

Institute on Drug Abuse, 1977. pp. 54-77.

De La Garza Gutierrez, F. Biomedical study of 30 patients using inhalants.

In: Sharp, C.W. and Carroll, L.T., eds. Voluntary Inhalation of Industrial

Solvents. Rockville, MD: National Institute on Drug Abuse, 1978. pp.

187-197.

189
DiMaio, V.J.M., and Garriott, J.C. Four deaths resulting from abuse of

nitrous oxide. J Forensic Sci 23(1):269-272, 1978.

Filley, C.M.; Heaton, R.K.; and Rosenberg, N.L. Neurology 40:532-539, 1990.

Foerster, E.H., and Garriott, J.C. Analysis for volatile compounds in biological samples. J Anal Toxicol 5:241-244, 1981.

Garriott, J.C.; Foerster, E.; Juarez, L.; De La Garza, F.; Mendiola, I.; and

Curoe, J. Measurements of toluene in blood and breath in cases of solvent abuse. Clin Toxicol 18(4):471-479, 1981.

Garriott, J.C.; Juarez, L.; Foerster, E.; and Curoe, J. Toluene detection in

cases of inhalant abuse. Forensic Sci Gazette 10(4):2-3, 1979.

Garriott, J.C., and Petty, C.S. Death from inhalant abuse: Toxicology and

pathological evaluation of 34 cases. Clin Toxicol 16(3):305-315, 1980.

Garriott, J.C., and DiMaio, V.J.M. Unpublished case studies.

Hayden, J.W.; Peterson, R.G.; and Bruckner, J.V. Toxicology of toluene

(methyl benzene): A review of current literature. Clin Toxicol 11(5):549-

559, 1977.

Joe, G.W.; Garriott, J.C.; and Simpson, D.D. Physical symptoms and psychological distress among inhalant abusers. Hispanic J Behav Sci 13(3):297-

314, 1991.

Korman, M.; Trimboli, F.; and Sender, I. A psychiatric emergency room study

of inhalant use. In: Sharp, C.W., and Carroll, L.T., eds. Voluntary

Inhalation of Industrial Solvents. Rockville, MD: National Institute on

Drug Abuse, 1978. pp. 137-158.

Korman, M. Clinical evaluation of psychological factors. In: Sharp, C.W., and

Brehm, M.L., eds. Review of Inhalants: Euphoria to Dysfunction. NIDA

Research Monograph 15. Rockville, MD: National Institute on Drug

Abuse, 1977. pp. 30-53.

Kurt, T.L.; McAnalley, B.H.; and Garriott, J.C. Lead encephalopathy from

gasoline sniffing: Successful treatment with chelation. Texas Med 78:52-

54, 1982.

190
Marshall, B.E., and Wollman, H. General anesthetics. In: Goodman and

Gilman’s The Pharmacological Basis of Therapeutics. 6th ed. New York:

MacMillan, 1980. p. 289.

Poklis, and Burkett, C.D. Gasoline sniffing. J Toxicol Clin Toxicol 11(1):35-

41, 1977.

Prockop, L., and Couri, D. Nervous system damage from mixed organic

solvents. In: Sharp, C.W., and Brehm, M.L., eds. Review of Inhalants:

Euphoria to Dysfunction. NIDA Research Monograph 15. Rockville,

MD: National Institute on Drug Abuse, 1977. pp. 185-199.

Rosenberg, N.L.; Kleinschmidt-DeMasters, B.K.; Davis, K.A.; Dreisbach,

J.N.; Hormes, J.T.; and Filley, C.M. Toluene abuse causes diffuse central

nervous system white matter changes. Ann Neurol 23(6):611-614, 1988.

Taylor, G., and Harris, W. Glue sniffing causes heart block in mice. Science

170:866-868, 1970.

Zur, J., and Yule, W. Chronic solvent abuse. Relationship with depression.

Child Care Health Devel 16(1):21-34, 1990.

Author

James C. Garriott, Ph.D., D-ABFT

Chief Toxicologist

Office of the Bexar County Medical Examiner

and Regional Crime Laboratory

600 N. Leona Street

San Antonio, TX 78207

and

Associate Professor

Department of Pharmacology and Pathology

University of Texas Southwestern Medical School at San Antonio

San Antonio, TX 78207

191

Sudden Sniffing Death

Following Inhalation of Butane

and Propane: Changing Trends

Earl Siegel

Suman Wason

Volatile substance abuse has been noted as a serious problem in Britain since

the 1970s (Editorial, Lancet 1988). In the United Kingdom two deaths from

solvent abuse were reported in 1971 and almost 1,000 deaths since then

(Ramsey et al. 1989; Johns 1991). One fifth of these deaths were apparently

first-time users (Johns 1991). Among products abused by the British

teenager, in order of decreasing frequency, are toluene-containing glues, chlorinated hydrocarbons (cleaning fluids, paints, varnishes, lacquers, dyes), acetone (nail polish remover, polystyrene cements), and gasoline, butane, and

propane (lighter fuels and bottled gases) (Editorial, Lancet 1988). The largest

number of deaths resulted from exposure to butane and propane (gas fuels or

propellants) (Johns 1991). In a survey from the United Kingdom, deaths due

to abuse of volatile substances occurred primarily in male teenagers (95 percent) of all social classes. Twenty-five percent were due to butane or propane.

The causes of death were direct toxic effects (51 percent), asphyxia (21 percent), aspiration of gastric contents (18 percent) and trauma (11 percent)

(Anderson et al. 1985).

The profile of American teenagers who abuse volatile substances fits a slightly

different pattern (see chapters by Beauvais, Smart, and Fredlund in this volume). A recent U.S. survey indicated almost one in five eighth-graders have

193
experimented with inhalant abuse (Johnston et al. 1992). By contrast with the

United Kingdom, experience with propane and butane inhalation appears to

be more limited in the United States. There are only limited reports of deaths

in the United States due to inhalation abuse. However, reports of the

American Association of Poison Control Centers annual data, which reflects

the experience of approximately 70 poison control centers across the United

States from 1987 to 1990, are an indicator and are summarized in table 1

(Litovitz et al, 1988, 1989, 1990, 1991). Details were provided for only four

cases (table 2). They were all young adults aged 14 to 20 years. We believe

that this and other published data underrepresent the true numbers of fatalities related to propane and butane abuse for the following reasons: (a) the

circumstances surrounding death may be misrepresented to coroners, (b)

volatiles are not easily or routinely screened for in cases of sudden sniffing

death, and (c) there, is no formalized registry of this form of drug abuse.

Death resulting from deliberately inhaled aerosol propellants for the purpose

of getting high was first reported in 1970. The cause of death was attributed

to cardiac dysrhythmia induced by the fluoroalkane propellants, trichlorofluoromethane (Freon 11) and dichlorodifluoromethane (Freon 12) (Bass 1970).

Because evidence indicated that continued discharge of these fluoropropellants would lead to a decrease in atmospheric ozone concentrations, and result in climatic changes and skin cancer, the Food and Drug Administration

called for a ban of chlorofluorocarbons in aerosol products in 1978 (Molina

and Rowland 1974). Most manufacturers replaced the Freon propellants with

isobutane, n-butane, isopropane, and isopentane. In 1986, we reported the

first human case of ventricular tachycardia after the accidental inhalation of

n-butane and isobutane, suggesting that these replacement propellants, too,

had potential for inducing fatal dysrhythmia in humans and animals (Wason

et al. 1986; Final report of the safety assessment, 1982).

Teenagers have continued to seek products other than fluorocarbons, for

their “highs.” Inhalation of gasoline, previously a well-known problem among

American Indians and lower socioeconomic teenagers, has become more

prevalent among all teenagers (Edminster and Bayer 1985). Also, the use of

194
Table 1. American Association of Poison Control Center inhalant abuse

related deaths

Year No. of inhalant abuse No. caused by

related deaths butane/propane

1987 10 1

1988 12 7

1989 25 9

1990 20 10

Table 2. Details of sudden sniffing deaths due to propane and butane

Age Sex Product Symptoms/Signs Post mortem drug

17

16

16

16

M Nail-enamel dryer Collapse Propane/

isobutane

M Air freshener Coma Not reported

Ventricular

fibrillation

M Butane lighter Collapse Butane

fluid

M Butane lighter Collapse/electro- Butane

fluid mechanical

dissociation

195
typewriter correction fluids frequently occurs and has resulted in sudden

sniffing deaths among teenagers following deliberate inhalation (King et al.

1985); this fluid contains trichloroethane and trichloroethylene.

Although not a comprehensive sample, table 3 identifies several cases brought

to the authors’ attention from the Tristate area surrounding Cincinnati, in the

latter part of 1991. These and those in table 2 compile only a portion of the

total deaths in the United States due to these replacement hydrocarbon

propellants.

Two recent fatalities attributed to propane and butane abuse serve to emphasize the potential for sudden death. The ready availability of these products

makes it imperative that health care providers and youth counselors across

the United States are aware of this problem (Siegel and Wason, 1990).

March 1990: An 11-year-old boy collapsed in a movie theater

bathroom. A butane cigarette lighter fuel container and a

plastic bag were found next to him. He also had several bottles

of typewriter correction fluid in his pocket. Cardiopulmonary

resuscitation was instituted; efforts proved unsuccessful and

he was pronounced dead shortly thereafter. Post mortem

examination showed no evidence of organic disease or

anatomic cause of death. Toxicologic analysis confirmed the

presence of butane in the patient’s blood and lung tissue.

Trichloroethane and trichloroethylene were not detected in

the patient’s blood or tissues.

April 1990: a 15-year-old boy was found unconscious in a

backyard. Three companions related that the four teenagers

had taken a 20-gallon propane tank from the family gas grill,

placed some of the gas in a plastic bag and were inhaling it in

order to get high. They also engaged in “torch breathing”

whereby they purposefully exhaled the propane gas and ignited

it. The subject collapsed soon after inhaling the gas; fumes,

ignited by a match, resulted in a flash fire. The patient did not

sustain any burns. He could not be resuscitated and died en

route to the hospital. Post mortem examination in this case,

too, failed to reveal an organic cause of death. Propane was

detected in the blood and lung tissues.

196
Table 3. Other selected Midwestern cases

Date Age Sex Origin Comments

7/91 16 M Kokomo, IN

8/91 16 M West Michigan

10/91 16 M Dayton, OH

10/91 15 M Noblesville, IN

11/91 14 M Madisonville, KY

11/91 29 M Portsmouth, OH

12/91 17 M West Michigan

Inhaling lighter fuel while driving with

friends, held his head out of the window

gasping for air and then crashed.

Autopsy showed no anatomic or

traumatic cause of death

Died after inhaling butane lighter fluid

1 of 4 boys inhaling butane lighter fuel

died

Died after inhaling aersolized* shoe

protectant

Died from inhaling aerosolized* solvent

Died after sniffing aerosolized* paint

1 of 3 boys inhaling butane lighter fuel

died

*Aerosol blends usually contain isobutane, n-butane, and propane.

Also, in January 1991 four teenagers huffing butane in a parked car in

Jefferson County, Kentucky, sustained facial and upper body burns from an

explosion ignited by a spark from the car lighter.

In addition, in October 1991 a 6-year-old boy imitating his older brother

huffing aerosolized room deodorizer was hospitalized.

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Interviews with friends and school officials revealed that sniffing of butane

lighter fuel is a common practice among many children at upper middle class

schools in Cincinnati. The second subject was avowedly antidrugs and did not

consider sniffing to be “drug abuse.” Ironically, his mother had discussed the

first fatality with him. His response was that the dead teenager was “probably

doing it wrong,” again attesting to the unfortunate, uneducated familiarity

with this form of abuse. Many empty butane canisters were subsequently

found in this teenager’s bedroom.

There are few reports of nonfatal incidents with “butane abuse”. Inhalation of

butane lighter fluid by a 15-year-old boy, reported in the British literature,

resulted in severe anterior chest pain, agitation, and collapse. In the emergency department, ventricular fibrillation occurred; this condition reverted to

sinus rhythm after cardioversion and lidocaine treatment (Gunn et al. 1989).

There is also some reported experience with “fire breathing” or “torch

breathing” after butane inhalation. Cartwright reported a 19-year-old fire

breather who inhaled butane gas from a cigarette lighter and then ignited it

after forcible exhalation (Cartwright et al. 1983). The subject suffered dyspnea, fever, malaise, and hypoxia and had extensive pulmonary infiltrates.

Marsh (1984) reported the case of a 14-year-old boy who developed hemorrhagic esophagitis and gastritis after repeated fire breathing.

A recent report details a 17-year-old adolescent’s propane abuse practices

(Wheeler et al. 1992). The authors speculate that the practice may be

widespread.

Several sudden sniffing deaths due to propane and butane have been presented. Since the abandonment of fluorocarbons, replacement fuels and propellants (such as butane and propane) probably represent the most common

sudden sniffing death hazard. Health care providers need to be aware that the

profile of the teenager who inhales volatiles does not include only the ethnic

lower socioeconomic classes. Reported investigations and many other communications lead us to believe that abuse of these readily available inhalants

has reached epidemic proportions, indicating an urgent need for preventive

efforts directed at teenagers and their parents with emphasis on the risk of

sudden sniffing death.

198
References

Anderson, H.R.; Macnair, R.S.; and Ramsey J.D. Deaths from abuse of

volatile substances: A national epidemiological study. Brit Med J

290:304-307, 1985.

Bass, M. Sudden sniffing death. JAMA 212:2075-2079, 1970.

Cartwright, T.R.; Brown, D.; and Brashear, R.E. Pulmonary infiltrates following butane fire breathing. Arch Intern Med 143:2007-2008, 1983.

Editorial: Complications of chronic volatile substance abuse. Lancet 2:431-

432, 1988.

Edminster, S.C., and Bayer, M.J. Recreational gasoline sniffing: acute gasoline intoxication and latent organolead poisoning. J Emerg Med 3:365-

370, 1985.

Final report of the safety assessment of isobutane, isopentane, n-butane, and

propane. J Am Coll Toxicol 1(4):127-142, 1982.

Gunn, J.; Wilson. J.; and Mackintosh, A.F. Butane sniffing causing ventricular fibrillation. Lancet 1:617, 1989.

Johns, A. Volatile solvent abuse and 963 deaths. Brit J Add 86:1053-1056,

1991.

Johnston, L.D.; Bachman, J.G.; and O’Malley, P. Questionnaire Response

from the Nation’s High Schools. Ann Arbor: Institute for Social

Research, 1992.

King, G.S.; Smialek, J.E.; and Troutman, W.G. Sudden death in adolescents

resulting from the inhalation of typewriter correcting fluid. JAMA

253:1604-1606, 1985.

Litovitz, T.L.; Bailey, K.M.; Schmitz, B.F.; Holm, K.C.; and Klein-Schwartz,

W. 1990 Annual report of the American Association of Poison Control

Centers National Data Collection System. Amer J Emerg Med 9:461-509,

1991.

199
Litovitz, T.L.; Schmitz, B.F.; and Bailey, K.M. 1989 Annual report of the

American Association of Poison Control Centers National Data

Collection System. Amer J Emerg Med 8:394-442, 1990.

Litovitz, T.L;, Schmitz, B.F.; and Holm, K.C. 1988 Annual report of the

American Association of Poison Control Centers National Data

Collection System. Amer J Emerg Med 7:495-545, 1989.

Litovitz, T.L.; Schmitz, B.F.; and Matyunas, N. 1987 Annual report of the

American Association of Poison Control Centers National Data

Collection System. Amer J Emerg Med 6:479-515, 1988.

Marsh, W.W. Butane firebreathing in adolescents: a potentially dangerous

practice. J Adol Health Cure 5:59-60, 1984.

Molina, M.J., and Rowland, F.S. Stratospheric sink for chlorofluoromethanes: Chlorine atomc-ata-lysed of ozone. Nature 249:810-812, 1974.

Press, E., and Done, A.K. Solvent sniffing. Pediatr 39:451-461, 1967.

Ramsey, J.; Anderson, H.R.; Bloor, K.; and Flanagan, R.J. An introduction to

the practice, prevalence and chemical toxicology of volatile substance

abuse. Hum Toxicol 8:261-269, 1989.

Siegel, E., and Wason, S. Sudden death caused by inhalation of butane and

propane. N Engl J Med 323:1638, 1990.

Wason, S.; Gibler, B.; and Hassan, M. Ventricular tachycardia associated with

non-freon aerosol propellants. JAMA 256:78-80, 1986.

Wheeler, M.G.; Rozycki, A.A.; and Smith, R.P. Recreational propane inhalation in an adolescent male. Clin Toxicol 30:135-39, 1992.

200
Authors

Earl Siegel, Pharm.D.

Associate Director

The Drug and Poison Information Center

and

Department of Emergency Medicine

University of Cincinnati

Cincinnati. OH 45229

Suman Wason, M.D., M.B.A.

Chief Toxicologist

The Drug and Poison Information Center

and

Division of Ambulatory Services

Children’s Hospital Medical Center

and

Department of Emergency Medicine

Department of Pediatrics

University of Cincinnati

Cincinnati, OH 45229

201

Treatment of Volatile Solvent

Abusers

Pamela Jumper-Thurman

Fred Beauvais

Even a cursory reading of the chapters in this volume leads to an inescapable

conclusion: Volatile solvent abusers are among the most difficult and

refractory people to deal with from a treatment perspective. The research on

background and psychosocial characteristics show this group to typically have

serious, multiple problems that lead to dysfunction in a wide range of social

and personal contexts. Most treatment programs are not equipped to deal

with the intensity of problems that solvent abusers present. Further adding to

the difficulty in the treatment of volatile solvent abuse is the lack of even a

rudimentary treatment model. Solvent abusers present a rather unusual

clinical profile, and in many respects they do not fit well within existing

treatment regimens. The lack of knowledge about solvent abuse treatment is

reflected in the routine and often frantic appeals for information from drug

abuse treatment programs. Drug abuse professionals who have an interest in

volatile solvent abuse or who have conducted even minimal research are

routinely queried for any information that would be helpful in addressing

treatment issues. These pleas are commonly from remote areas that are

experiencing extremely high rates of solvent use and are nearly devoid of

effective resources. The lack of good information,

even well-established drug abuse treatment programs are often at a loss as to

also, is widespread and

how to approach solvent abusers.

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From time to time, there is an effort to build a volatile solvent abuse treatment program that will serve these populations, but it is our estimate that

these programs rarely survive for more than 9 months. The expense of this

type of treatment, the lack of trained treatment staff (in fact, little is known

about what training should consist of), and the staff demoralization over the

ineffectiveness of treatment seem to be the major elements leading to the

failure of these program efforts. Generally volatile solvent abuse has low visibility in most communities and even among treatment professionals, resulting

in a lack of funds for targeted treatment. It is quite possible that this will

change in the coming years if the trend toward increasing use of solvents

among adolescents continues. (See Beauvais, this volume.)

In this chapter we will attempt to outline the critical elements that should be

included in volatile solvent abuse treatment. These recommendations are not

derived from any particular theory of treatment, nor are they based on a theory of volatile solvent abuse. Indeed, as already pointed out, such a theory

does not exist. The basis of what follows will be the characteristics of solvent

abusers as they have been discovered through research and upon which there

is some consensus among the various studies. It is hoped that, as more experience and knowledge are gained in volatile solvent abuse treatment, we will

arrive at a point where treatment efforts can be more theoretically grounded

and more effectively focused.

Treatment of volatile solvent abuse has a great deal of overlap with drug

abuse treatment in general, and many of the techniques and approaches used

in the usual treatment programs do have a place in volatile solvent abuse

treatment. Those general treatment approaches, however, will not be

addressed here; rather, the focus will be on the specific issues that are related

to volatile solvent abuse treatment.

Assessment and Detoxoification

Oetting and Webb (this volume) make it abundantly clear that volatile solvent

abusers are typically beset by numerous psychological and social problems in

addition to their abuse of chemicals. If treatment is to be effective it must

address each of these problem areas.

At the outset it is important to make the distinction between solvent abusers

and those individuals who may have used solvents once or twice, or who may

204
have experimented with them for a brief period of time. The ubiquity of

commercial solvents and the natural curiosity of youths make it likely that

most young people have had a least a passing encounter with inhaling chemicals for their euphoric effects. For the most part, however, this is time limited

and there are no lasting negative consequences. (The exception to this is the

naive experimenter who may die from the use of a particularly lethal solvent.)

The picture for solvent abusers, however, is much different and their lives become consumed with the obtaining and use of solvents. Oetting and Webb

(this volume) and the DSM-IIIR (American Psychiatric Association 1987)

provide some guidance in making the distinction between “benign” solvent

users and chronic solvent abusers who are in need of treatment.

While physical examinations are normally a part of the intake procedure in

most drug abuse programs, they take on added importance for solvent

abusers. There are a number of specific medical complications that must be

assessed. Sharp and Rosenberg (1991) point out that renal and hepatic

abnormalities are often associated with chronic solvent abuse and, where

leaded gasoline is still widely in use, lead poisoning is common. Furthermore,

there is also a possibility of cardiac arrhythmias and pulmonary distress.

Many solvent abusers are lacking in basic life skills, including personal

hygiene, leading to potential problems with skin diseases and poor nutrition.

In general, a thorough medical examination is needed with special attention

to those conditions resulting from chronic solvent abuse. Clients brought in

to treatment during acute intoxication may have other immediate medical

crises that need attention.

The families of abusers are quite often highly dysfunctional, and it is not

uncommon for the abuser to have been raised in a home without a father.

This raises the need for a thorough assessment of family stability, structure,

and dynamics so that treatment can be focused on such needs as therapeutic

intervention with the family or providing reparenting or social bonding skills

for the client. In many cases the family situation may be so chaotic that one of

the treatment goals may be to work toward foster care for younger abusers or

halfway house placement for older adolescents.

One of the common findings in research studies of solvent abusers is the presence of neurological impairment. Unfortunately, much of this research is

flawed in that there is no control for the possibility that these problems may

have predated the use of solvents. It would be important to know if there are

205
underlying conditions such as learning disabilities that may have contributed

to the constellation of premorbid dysfunctional behaviors. There is some

speculation that solvent abusers are self-selected in the sense that their early

neurological and behavioral problems are somehow implicated in their later

choice to use solvents. A thorough examination of records of any early neuropsychological testing and of school records would help frame the need for

the remediation of specific problems during the course of treatment.

Unfortunately, not a great deal is known about the extent and duration of

neurological damage caused by solvents. (See reviews by Rosenberg and

Sharp, and Tenenbein, this volume.) There are a number of studies that

reveal that heavy solvent users do indeed incur damage; however, the duration

and/or reversibility of this damage is unclear. The majority of volatile solvents are lipophilic, meaning that they are stored in fatty tissue in the body

and are eliminated much more slowly than most other drugs. One consequence of this is that solvent users may be experiencing residual effects from

the drugs for quite some time (due to the deposit of solvents in the white matter of brain), including altered affect and dullness of intellectual functioning.

The implication for treatment is that the period of detoxification for solvent

abusers may need to be longer than that of other drugs of abuse. It is quite

possible that much of the frustration with treating solvent users is that very

few short-term treatment gains can be achieved. Solvent abusers simply are

not able to capitalize on the therapies that are typically used in treatment

programs until the abusers have recovered sufficient cognitive and emotional

functioning. There are absolutely no data to indicate how long it will take

solvent abusers to recover to the point at which they are capable of actively

engaging in the recovery process. This no doubt will be subject to individual

differences, the level of premorbid functioning, and the duration and level of

solvent abuse. Any neurological or neuropsychological testing done early in

the course of treatment should be repeated in several months to assess the

possibility that any measured deficits have improved with time in treatment.

Peers have been consistently implicated as the most powerful influence on

adolescent use of drugs (Oetting and Beauvais 1986). This influence may be

even more salient for solvent abusers since the peer clusters (see Oetting and

Webb, this volume) of solvent abusers can be highly deviant, thus making

them more impervious to positive social influences. Assessment should take

into account both the structure and norms of the abuser’s peer cluster so that

a treatment goal can be established to break those social bonds and replace

206
the cluster with a more constructive group of peers. Achievement of this goal

can be enhanced if there is knowledge of the particular dynamics that attracted the client to the peer cluster. Leal et al. (1978), for instance, describe

groups of street children in Mexico City who have left their homes at early

ages and have joined other groups of children in a structure that basically

recreates the family. The older adolescents provide protection and direction

for the younger children, but they also direct much of the street crime that is

utilized to acquire solvents, the use of which is the norm in the group and is

quite extensive. While this is an extreme example, it does illustrate that the

peer structure has a basic meaning for these youths and that certain primary

needs are being met by the group. It should be possible to discern similar

meaning by examination of the peer cluster structure of solvent abusers in

treatment.

The role played by siblings of solvent abusers should not be overlooked. In

many instances there is a pattern of use by brothers and sisters or even

cousins, a case in which treatment must be extended to all members of the

family involved with solvents. This pattern has been found quite often among

minority children where the extended family may live within close proximity.

Older adolescent solvent abusers are also most likely using other drugs. It is

important to obtain an accurate drug use history in order to assess any problems created by this use and to understand the drug taking motivation of individuals. It is useful to know if the use of solvents has a different meaning for

the individual than the use of other drugs. The drug history should also involve as thorough a knowledge as possible of the types of solvents that have

been used. Most of the time it is not possible to link a specific solvent with a

specific neurological or behavioral symptom, but in some instances important

insights can be gained. For instance Pryor (this volume) reports essentially irreversible peripheral neuropathies from exposure to hexanes, toluene, and

other solvents. As stated, this type of assessment is very difficult due to the

wide range of solvents and solvent mixtures that may have been used as well as

denial or poor recall from the patient.

Length of Treatment

Treatment programs for solvent abusers, then, should be prepared to engage

their clients in an extended period of supportive care marked by abstinence

from solvents, nonconfrontation, and an emphasis on developing basic life

207
skills. Initial intervention should be very brief (e.g., 20-minute sessions as

opposed to 60 minutes) and concrete. Attention span and complexity of

thinking are greatly reduced for many solvent abusers when they first enter

treatment. Clients should be monitored to assess their changing level of functioning to determine at what point they are cognitively ready for increasing

levels of therapeutic intervention. Data on the optimum length of treatment

are nonexistent, although some programs are recommending as long as 2

years (Driver 1991-92).

One of the drawbacks to extended periods of treatment is the possibility of

bringing people together who are likely to form deviant peer clusters within

the treatment environment. Given a sufficient amount of time, like-minded

people will tend to coalesce and create peer clusters that can subvert treatment. Staff need to be aware of these dynamics and develop strategies for

intervening when relationships form that are detrimental to the therapy goals.

Intensive aftercare and followup are essential for volatile solvent abusers.

They need particular assistance in creating a healthy social milieu, since in all

likelihood their social contacts have been limited to other solvent abusers and

otherwise deviant peers. For younger abusers the school environment may be

especially difficult to readjust to. There they will find it difficult to avoid

many of the people they previously associated with, and it is likely that they

have developed poor relationships with the school teachers and staff. It is

important to have a school counselor or other staff person who will be

involved in discharge planning and who will act as an advocate for the client

in the school. In addition, it is advisable that someone be responsible for

closely monitoring the behavior of treated abusers so that help can be made

immediately available at the first sign of relapse into previous behavior patterns. Big Brother/Sister programs are especially helpful for previous solvent

abusers.

Inpatient Versus Outpatient Treatment

In the treatment of substance abusers, there is always the question of whether

inpatient or outpatient treatment is the most appropriate. There are no

clear-cut guidelines for this. However, there are several characteristics of solvent abusers that make inpatient treatment the most appropriate choice. The

typically chaotic family situations make it unlikely that the abuser will receive

adequate support from the family for treatment goals. Quite the opposite, it

208
is more likely that family members will subvert therapeutic efforts. In particular, these families often have very little control over the behavior of the

abuser, making abstinence from solvents very difficult.

The highly deviant and powerful peer clusters of solvent abusers also make

behavior change unlikely in an outpatient setting. The solvent abuser has

typically restricted his or her relationships to other solvent abusers, leaving

these peer clusters as the only source of socialization. The antisocial nature

of these groups makes adherence to therapeutic aims nearly impossible.

Furthermore, solvent abusers spend the great majority of their time either

obtaining solvents or being under their influence. This leaves little time for

positive or socially acceptable interactions.

As a group, solvent abusers are very impulsive and elusive, making treatment

compliance very difficult. As outpatients they may avail themselves of treatment for short periods of time but they soon “disappear” into their previous

milieu where they are extremely difficult to locate (N. Rosenberg, personal

communication, July 1990). Inpatient treatment provides the structure and

control needed to get abusers through the extended detoxification period and

to a point where they can begin to experience the positive effects of treatment.

The elusiveness of solvent abusers contributes to making them a “hidden”

population in need of treatment. They rarely volunteer to come into treatment, and their disenfranchisement from the family makes it less likely that

the family will bring them into treatment. Case finding for solvent abusers is

difficult, and a great deal of reliance must be placed on referral sources such

as the police, welfare workers, homeless shelters, hospital emergency rooms,

and runaway shelters. Hospitals are a source; however, few subjects are

referred by this process as they seldom seek or require treatment in a hospital

setting.

More so than other drug abusers, it is necessary to have some type of leverage

to keep solvent abusers in treatment. Neither the abusers nor their families

have the motivation to endure the effort and extended time that is necessary

for effective treatment. Ironically, the highly dysfunctional behavior of the

families of solvent abusers can often provide the route to treatment. These

families are quite often abusive and have a history of contact with police or

welfare agencies. This record can often provide the leverage for placing a

young person in treatment.

209
The law itself, that is, the existence of penalties for the use of solvents, is

another common source of leverage. Whether or not one believes that laws

can control drug abuse, in instances like this, legal clout can at least provide

the vehicle by which highly dysfunctional individuals can be brought into

treatment. Reed and May (1984) provide evidence that solvent abusers, even

more so than other drug abusers, have a greater history of criminal involvement. Unfortunately, the legal status of solvent inhalation is highly variable,

with some jurisdictions having no legal controls or interdiction directly

relevant to solvent abusers.

Designated Treatment Programs

Solvent abusers appear to present enough differences in their clinical profile

to suggest that they cannot be treated in the context of programs that work

with drug abusers in general. The extended period of detoxification and

recovery of neurological function, the relative unresponsiveness to early

treatment efforts, and the multitude of collateral problems dictate that, in

general, solvent abusers need to be treated in separate programs.

One of the problems in treatment of solvent abusers to this point is the frustration on the part of treatment staff over the slow rate of recovery. If staff

expectations are not appropriate to the level and pace of progress that can be

reasonably achieved, there will undoubtedly be low morale.

Specific treatment programs for solvent abusers are undoubtedly an expensive

proposition; yet, given the nature of this problem, this seems the only logical

and effective approach.

Special Emphases in Treatment

Adding to the expense of solvent abuse treatment is the broad array of intervention strategies that are required if lasting change is to be effected. Solvent

abusers are typically deficient in a variety of skills needed for effective living.

While most drug abusers needing treatment also have personal/social problems that need attending to, solvent abusers are marked by the extent and

depth of these characteristics. Following are areas where special attention is

needed in the treatment of solvent abusers.

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1. Extensive involvement of the family to ensure compliance with treatment goals after treatment. Alternate placement should be explored.

2. Remediation of academic deficits to ensure adequate posttreatment

school adjustment for younger abusers.

3. Vocational training for older abusers to promote self-sufficiency.

4. Training in basic life skills including personal hygiene and nutrition.

5. Advocacy with the justice system.

6. Restructuring of social environment to exclude peers who are detrimental and include nondeviant peers.

7. Extensive aftercare and followup.

Summary

Those contemplating treatment of solvent abusers must be prepared to work

with individuals who have a greater breadth and depth of personal and social

problems. Treatment can be expected to be long term, possibly up to 2 years

with an extended period of detoxification before any specific therapeutic

interventions can be attempted. A wide range of interventions will be necessary to address the multiple social problems experienced by the typical solvent

abuser.

The effective treatment of solvent abusers is likely to be an expensive proposition, yet, given our current level of knowledge of treatment, there is no alternative. The cost of volatile solvent abuse treatment must be weighed against

further costs for this high risk population, including incarceration, medical

expenses, and welfare support.

Research Agenda

The above discussion leads to a number of gaps in our knowledge of solvent

abuse treatment that can be addressed in future research. They are as follows:

211
1.

2.

3.

4.

5.

6.

7.

8.

Are there specific neurological deficits caused by solvents that can be

remedied with specific treatment techniques? Can these be discerned

by the type of solvent?

Can guidelines be developed that would indicate when reversibility of

neurological damage will occur? Can a timetable or list of

benchmarks be developed that would indicate when higher order

cognitive therapies would be effective?

Are there specifiable premorbid characteristics that lead to solvent

abuse? Can these be addressed in treatment?

Are there certain therapeutic approaches that are more appropriate

for solvent abusers?

What are the family characteristics that indicate that discharge back to

the family would or would not lead to continued therapeutic progress?

Are there socioeconomic factors that contribute to solvent abuse?

Are there highly structured outpatient settings where there is

sufficient control to provide treatment?

What incentives/leverage can be applied to ensure treatment

compliance?

References

American Psychiatric Association. (1987). Diagnostic and Statistical Manual

of Mental Disorders (3d. ed., rev.) Washington, DC: the Association.

Driver, D. Two year residential program designed to help solvent abusers.

The Journal (Dec. 1991-Jan. 1992). p.3.

Leal, H.; Mejia, L.; Gomez, L.; and Salinas de Valle, O. Naturalistic study of

inhalant use in a group of children in Mexico City. In: Sharp, C.W., and

212
Carroll, L.T., eds. Voluntary Inhalation of Industrial Solvents. Rockville,

MD: National Institute on Drug Abuse, 1978.

Oetting, E., and Beauvais, F. Peer cluster theory: Drugs and the adolescent. J

Counsel Devel, 65:17-22, 1986.

Reed, B., and May, P. Inhalant abuse and juvenile delinquency: A control

study in Albuquerque, New Mexico. Int J Addict, 19:789-803, 1984.

Sharp, C.W. Clinical and medical manifestations of volatile solvents. In: Arif,

A.; Grant, M.; and Navaratnam, V., eds. Abuse of Volatile Solvents and

Inhalants: Papers Presented at a W.H.O. Advisory Meeting. Penang,

Malaysia: W.H.O. Training Center, Universiti Sains Malaysia, 1988. pp.

227-282.

Sharp, C.W., and Rosenberg, N.L. Volatile substances. In: Lowinson, J.H.;

Ruiz, P.; Millman, R.B.; and Langrod, J.G., eds. Substance Abuse—A

Comprehensive Textbook. 2d ed. Baltimore: Williams & Wilkins, 1991.

pp. 303-327.

Authors

Pamela Jumper-Thurman, Ph. D.

and

Fred Beauvais, Ph. D.

Tri-ethnic Center for Prevention Research

Colorado State University

Fort Collins, CO 80523

213

A Longitudinal Study of Inhalant

Use: Implications for Treatment

and Prevention

D. Dwayne Simpson

Evaluation of prevention and treatment paradigms for dealing with inhalant

users has received limited attention. As described elsewhere in this volume

(see chapters by Octting and Webb and by Beauvais) and earlier by McSherry

(1988) and Santos de Barona and Simpson (1984) these drug users are typically young and have poor life management skills. They are at high risk for

drug use and deviant behaviors due to their low socioeconomic opportunities,

poor educational background, disrupted family environment, poor psychological and emotional adjustment, and social discrimination. Treatment

agencies face a major task in dealing with these youths, compounded further

by the common problem of disintegrated families with parents who are emotionally despondent and have “given up on their kids.” As a result, counselors

at community-based intervention programs often become friends, school

teachers/tutors, role models, and surrogate parents for their clients, but the

emotional weight of these responsibilities leads to frequent burnout. Even

though there appears to be short-term gains for many clients while the therapeutic relationship is maintained, sustained progress is difficult and long-term

outcomes are frequently poor for these youths as a whole.

Little is known also about the etiological aspects and natural history of toxicant inhalant use. Sniffing or huffing of solvents and other inhalants often

appears to be part of a broader pattern of drug use, but the duration of use

215
and its role in the general psychosocial development of youths remains largely

unknown. Prospective research on the social and psychological correlates of

inhalant use is important for examining long-range consequences and implications of these factors for intervention efforts. This chapter therefore summarizes major findings from studies conducted based on the Texas Prevention

Management and Evaluation System (Santos de Barona and Simpson 1984),

a multisite data base that included followup research on Mexican-American

youths admitted to intervention services for inhalant users (see Simpson and

Chatham 1991).1

Description of the Sample

A total of 175 Mexican-American youths aged 13 to 17 when they entered the

Youth Advocacy (YA) Program in Austin, Texas, from 1981 to 1985 were targeted for followup. Their history of preadmission inhalant use showed that 20

percent used at least weekly in the 2 months prior to entering this program,

another 24 percent used at least once a month, 19 percent had used previously

but not in the prior 2 months immediately before admission, and 37 percent

had never used inhalants. This heterogeneous mix of high-risk youths represented an appropriate sample for the longitudinal study of drug use changes

and related outcomes over time. These clients stayed in the program an average of approximately 13 months, during which time they received individual

counseling and participated in a variety of recreational activities, cultural enrichment, academic tutoring, and related life-skills training. However,

detailed client participation records were not available in this study for

specifically evaluating these services.

Private face-to-face followup interviews were conducted during October 1987

to April 1988, an average of over 4 years after admission to the YA program.

Of the 175 cases in the target sample, 150 (86 percent) were successfully

traced; 110 (63 percent) gave informed consent and were interviewed, 9 (5

percent) refused to participate, 3 (2 percent) were deceased, 13 (7 percent)

were in prison and unavailable for interview, and 15 (9 percent) had moved

1

The Texas Prevention Management and Evaluation System data collection

forms for intake and followup are available from the author; also see Simpson

and McBride 1992.

216
outside the Austin metropolitan area. The remaining 25 (14 percent) could

not be located. Of the 110 completed cases, 79 percent of the mothers were

also interviewed.

Average age at program admission was just under 15, and 65 percent were

male. Reasons for coming to the YA program showed that 35 percent were

referred by legal authorities, 22 percent by school officials, 19 percent by parents or family members, and 12 percent were self-referrals; 68 percent had

friends who had been in the program before. They came predominantly from

low socioeconomic background (less than one in four of their parents had

finished high school), and only a third reported their parents were living

together.

Behavioral Changes From Program

Intake to Followup

When followed up—at average age 19—a third of the sample was either married (10 percent) or living as married (25 percent), and 8 percent were separated or divorced. Half had one or more children (68 percent for females).

Marital relationships of their parents had become further impaired, compared

with the time of intake. This was especially true among females; only 13 percent said their natural parents were living together.

When admitted to the YA program, two thirds of the youths were in school

(most had reached the eighth grade) and one third were suspended or had

quit school. Of those still in school, however, 41 percent had mostly failing

grades on their last report card, and over half had either skipped classes or

been in trouble at least once a week. Attitudinal ratings also showed that

school was not generally considered to be a high priority by these youths.

It was therefore not surprising to find that at followup, 71 percent of this

high-risk sample had dropped out of school. Only 9 percent had graduated or

received their GED, and 15 percent were still enrolled in school or a formal

vocational training program. Only half had been employed at a full-time job

for 1 or more months in the year before followup (including 56 percent of

males and 37 percent of females).

Before entering the YA program, most youths (85 percent) had been picked

up by the police at least once, and 77 percent had been arrested (which was

217
consistent with the high rate of legal referrals to the agency). During the year

immediately prior to the followup interview, the youths still were involved in

a high level of criminal activity. Over half (54 percent) had been arrested at

least once during the year, and 26 percent were arrested two or more times; 12

percent had spent at least 30 days in jail. Approximately one third of the

youths (31 percent) admitted to having committed serious crimes such as

theft, robbery, mugging, fighting with a weapon, or rape.

Historically, marijuana was typically used first (at about age 13, on average),

followed 6 months later by alcohol and then inhalants at age 14. Cocaine use

was initiated, on the average, after turning age 16. Almost all of the sample

(93 percent) had used alcohol before entering the YA program, and information on specific drinking patterns immediately before the followup interview

suggested there was a continuation of heavy alcohol involvement. That is, one

third drank on 15 or more days of the last month before followup, 26 percent

consumed an average of 4 ounces or more of 80-proof liquor equivalent per

day, and 40 percent had been drunk in the past month.

Prevalence of marijuana and inhalant use decreased somewhat from before

YA program intake to followup, but usage of several other drugs increased.

Figure 1 shows that marijuana was the drug used most often in the first

year—referred to as year 1—after termination from the YA program.

Seventy-four percent reported using it in the first year (and about 45 percent

of the sample reported using it at least weekly); this was down from a level of

87 percent of those using marijuana in the 2 months before entering YA program. The second most frequently used drug category in year 1 was uppers

(36 percent), while hallucinogens, inhalants, and cocaine were each used by

approximately one-fourth of the sample. Opiates and downers/depressants

were the least frequently used drugs (and are not shown in figure 1).

In the last year before the followup interview—referred to as year

4—marijuana was again the most frequently used drug (74 percent).

However, cocaine and other uppers were next in prevalence of use (31 and 30

percent), which was assumed to be due in part to their increased popularity

and availability during the time of this study. On the other hand, inhalants

were used by only 6 percent, and along with opiates and downers, were the

drugs used least frequently.

218
Figure 1. Drug use in years 1 and 4 after leaving YAP
The major reasons youths gave for using inhalants were easy availability,

curiosity, and the “high” resulting from sniffing or huffing (see Joe and

Simpson 1991). Personal adjustment problems as well as parental absence

and family relations were also important. Fortunately, very few individuals

continued long-term use of inhalants, and their reasons for quitting were

found to be primarily associated with family or social pressures and attitudinal

changes about its use (including concerns about health).

Followup Outcomes in Relation to Inhalant Use at Intake

One important aspect of this study was the comparison of followup outcomes

according to level of baseline (preadmission) inhalant use. These data are

summarized in table 1, but the small sample sizes call for caution in making

interpretations. Preliminary analyses indicated these four groups were generally comparable at intake in terms of sociodemographic characteristics. Most

interestingly, the use of alcohol and other drugs as well as legal involvement

measures were directly associated with the level of inhalant use. At followup,

the data presented in table 1 show these trends remained intact; thus, the

youths who were heavier inhalant users at intake continued to have more

negative outcomes 4 years later.

In particular, the group of weekly users had lower employment rates, higher

prevalence of arrests and illegal activity, and more drug use than the other

groups. At least two thirds of each group used illegal drugs in year 4 of the

followup; this was true of 95 percent of the weekly users. Furthermore, 45

percent of this group were also heavy drinkers who on the average consumed

over 4 ounces of 80-proof liquor equivalent per day.

The only exception to the continued tendency toward more general polydrug

use by the weekly inhalant use group is cocaine. Overall, preadmission use for

cocaine was 10 percent for the total sample, and it increased to 31 percent at

followup. In contrast to all other drug categories, the preadmission group of

weekly inhalant users had the lowest level of cocaine prevalence in year 4

(although the group differences were small and statistically insignificant).

Youths with more extensive inhalant use histories reported more cognitive

problems involving clarity of thinking, decisionmaking, concentration, and

remembering details. Depression, anxiety, and thoughts of suicide were also

common (see Smith et al. 1991). Almost half of the youths, for instance,

showed evidence of clinical depression and were highly anxious. Over one

220
Table 1. Behavioral outcomes at year 4 followup by preadmission inhalant use

Outcomes in Level of preadmission inhalant use Total

past year Weekly Monthly Experimental Never N

Days Employed (%)

Over 90 Days 38

Legal Involvement (%)

Arrested

Jailed

In illegal activity

76 58 43 49 54

71 53 38 41 48

76 50 52 55 59

Alcohol and Drug Use (%)

> 4 oz./day* 45

Using any illegal drug 95

Any marijuana 90

Any cocaine 24

Any other uppers 38

Any hallucinogens 29

Any inhalants 24

Sample Sizes 21

52 48 63 54

26 30 16 26

79 67 77 79

74 62 73 74

36 29 33 31

37 24 26 30

27 24 12 20

5 0 4 6

19 21 49 110

*Refers to ounces of 80-proof liquor equivalent drunk in the past month.

221
fourth had experienced suicidal thoughts, and one fifth had made at least one

suicide attempt. Psychological problems, including depression and low selfesteem, tended to be accompanied by other health problems or symptoms.

Integrative Prediction Model of Outcomes

Several measurement domains representing major conceptual areas (often

considered important in measuring drug use among youths) were examined as

part of a general multivariate prediction model, similar to previous efforts by

Huba et al. (1980), Jessor and Jessor (1977), Kandel (1978), Kaplan (1980),

and Oetting and Beauvais (1987). In particular, Joe et al. (1991) included cultural, socioeconomic, and other factors using causal modeling procedures

(Joreskog and Sorbom 1988) with the 4-year followup data. The results

showed that a conceptual path model in which influences of drug availability,

family relations, sociodemographic, and cultural domains are assumed to operate exclusively through peer and psychological mediators to explain drug

use was inadequate. Instead, a more integrated model allowing both direct

and indirect effects on the drug use criteria provided a better fit to the data.

At the same time, however, deviant peers exerted a primary influence on inhalant and other drug use at followup; family and environmental variables

tended to operate indirectly through this link. It was also found that measures of psychological adjustment or vulnerability (such as self-esteem,

depression, self-derogation, and learned helplessness) were not directly

predictive of drug use outcomes.

With respect to inhalant use history, one of the strongest predictors was education; lower education levels were associated with more extensive inhalant

use, especially total days of lifetime use and starting at an earlier age.

Inhalant use by other family members, usually older siblings, was another predictor for heavier use. Finally, indicators of perceived availability of inhalants

and acculturative stress also failed to demonstrate significant direct or indirect effects on inhalant use (also see Barrett et al. 1991).

Evaluations of Intervention Effects

Using during-program data from the YA program and three other similar

programs primarily serving Mexican-American youths, Barrett et al. (1988)

found that favorable changes occurred on behavioral indicators for alcohol

and drug use as well as legal and school problems during the first 3 months in

222
treatment. In particular, the results reflected the positive influence of traditional social bonding—as represented by family support and commitment to

religious involvement—on reducing problem behaviors over time. Decreased

exposure to drug-using peers during treatment was even more important as a

positive influence, however, supporting the widespread evidence for the role

of peer pressure and support networks. Severity of problems at the time of intake was also associated with the outcomes 3 months later, but these effects

appeared to be moderated by the impact of positive family and peer

influences.

Another important (and therapeutically encouraging) finding was that client

interest and motivation at the time of program intake were positively related

to level of participation in treatment, which in turn was related to improved

performance during the program. The results confirmed the frequent observations in the epidemiological literature that family, friends, and religion are

related to adolescent behaviors, but more importantly, these findings indicate

that the same relationships operate in the context of a therapeutic environment as well. The implications are that intervention efforts should (1) enhance efforts to capture family involvement and emotional support for the

youths, (2) increase contacts and rapport with positive peer and role models

while diverting relations with drug-using friends, and (3) focus efforts on ways

to maximize client interest in and commitment to the therapeutic enterprise.

These are not new goals, but it is important to explore new ideas for implementing ways to reach them.

Concluding Comments

It appears that intervention efforts are increasingly difficult after youths

become more heavily enmeshed in drugs and related problems. Low cost and

easy access to toxicant inhalants facilitate and encourage their use, but educational efforts and family support seem to help change attitudes and reduce

chronic or long-term usage. It is especially important to redirect adolescent

ties with deviant peers and destructive friendships. Feelings of discrimination

and alienation by youths need to be addressed through efforts to establish better social coping skills as well as reducing educational failures and school

dropout rates (see Menon et al. 1990). This may require that attention be

given to cultural heritage and identity for enhancing self-concepts, and considering alternative cognitive learning strategies that might be more effective

with some minority youths. Care for physical health must also be emphasized,

223
along with education about the growing threat of AIDS and lowering the frequency of teenage pregnancies by unwed parents. As stressed by McSherry

(1988), much of this effort revolves around the needs for basic life management skills and should help enhance socioeconomic opportunities and expectations that are critical for long-range solutions to many of the problems

experienced by these youths.

It is important to sustain and systematically refine intervention services in

community-based agencies that have the support and confidence of the neighborhood being served. Community trust, effective social service networking,

and organizational stability are important attributes of most successful programs. To evaluate the efficacy of their services, however, clinical efforts must

be carefully coordinated with comprehensive empirical assessments of the

intervention process and longitudinal outcomes. Comprehensive data systems should include community epidemiological indicators over time, along

with client and intervention process data collected throughout treatment.

Posttreatment followup assessments are also essential components of this

longitudinal evaluation model.

Toward this end, improved strategies are especially needed for involving parents and families of inhalant users, both behaviorally and emotionally, in the

therapeutic process to create a supportive environmental atmosphere for

positive change. Efforts to accomplish such family involvement and counseling have continued to prove difficult in some Mexican-American communities

(Jesse Flores, personal communication), suggesting that culture-sensitive

approaches may be required and that this represents a serious challenge for

intervention efforts (see Szapocznik and Kurtines 1989).

These represent extremely complex sociological problems and psychotherapeutic goals, and their solution is not the unique responsibility of drug abuse

prevention and treatment programs. In order for agencies to be realistic in

the scope and focus of their intervention objectives, identification of priority

concerns for their particular community and the planning of strategies

requires careful thought, expertise, discipline, and community mobilization.

Sustained attention and financial support for the progressive development of

effective intervention efforts are required, particularly among low socioeconomic groups with limited access to drug treatment and related services.

224
References

Barrett, M.E.; Joe, G.W.; and Simpson, D.D. Acculturation influences on

inhalant use. Hispanic J Behav Sciences 13(3):276-296, 1991.

Barrett, M.E.; Simpson, D.D.; and Lehman, W.E.K. Behavioral changes of

adolescents in drug abuse intervention programs. J Clin Psychol

44(3):461-473, 1988.

Huba, G.J.; Wingard, J.A.; and Bentler, P.M. Applications of a theory of drug

use to prevention programs. J Drug Educ 10:25-38, 1980.

Jessor, R., and Jessor, S.L. Problem Behavior and Psychosocial Development:

A Longitudinal Study of Youth. New York: Academic Press, 1977.

Joe, G.W.; Barrett, M.E.; and Simpson, D.D. An integrative model for drug

use severity among inhalant users. Hispanic J Behav Sciences 13(3):324-

340, 1991.

Joe, G.W., and Simpson, D.D. Reasons for inhalant use. Hispanic J Behav

Sciences 13(3):256-266, 1991.

Joreskog, K., and Sorbom, D. LISREL 7: A Guide to the Program and

Applications. Chicago: SPSS, 1988.

Kandel, D.B., ed. Longitudinal Research On Drug Abuse. Washington, DC:

Hemisphere, 1978.

Kaplan, H. Deviant Behavior in Defense of Self. New York: Academic Press,

1980.

McSherry, T.M. Program experiences with the solvent abuser in Philadelphia.

In: Crider, R., and Rouse, B., eds. Epidemiology of Inhalant Abuse: An

Update. Research Monograph 85. DHHS Pub. No. (ADM)88-1577.

Rockville, MD: National Institute on Drug Abuse, 1988.

Menon, R.; Barrett, M.E.; and Simpson, D.D. School, peer group, and

inhalant use among Mexican-American adolescents. Hispanic J Behav

Science 12(4), 1990.

225
Oetting, E.R., and Beauvais, F. Peer cluster theory, socialization characteristics, and adolescent drug use: A path analyses. J Counseling Psychol

34:205-213, 1987.

Santos de Barona, M., and Simpson, D.D. Inhalant users in drug abuse prevention programs. Amer J Drug Alcohol Abuse 10(4):503-518, 1984.

Simpson, D.D., and Chatham, L.R., eds. Inhalant use by Mexican-American

youth: Findings from a longitudinal study. Newburg Park, CA: Sage.

(Special issue of Hispanic Journal of Behavioral Sciences), 1991.

Simpson, D.D., and McBride, A.A. Family, Friends, and Self (FFS)

Assessment Scales for Mexican American youth. Hispanic J Behav

Sciences 14(3), 1992.

Smith, S.S.; Joe, G.W.; and Simpson, D.D. Parental influences on inhalant

use. Hispanic J Behav Sciences 13(2):267-275, 1991.

Szapocznik, J., and Kurtines, W.M., eds. Breakthroughs in Family Therapy with

Drug Abusing and Problem Youth. New York: Springer Publishing

Company, 1989.

Acknowledgment

Supported by National Institute on Drug Abuse Grant No. DA04393. Drs.

George W. Joe, Mark E. Barrett, Anthony A. McBride, Stephanie S. Smith,

and Wayne E.K. Lehman assisted in the analysis of data. Jesse Flores

(Director of the Youth Advocacy Program in Austin) assisted in the longrange planning and coordination of this project, and Thereza Glover and

Vera Hernandez supervised followup staff and fieldwork operations.

226
Author

D. Dwayne Simpson, Ph.D.

Director, Institute of Behavioral Research

Professor, Department of Psychology

Texas Christian University

P.O. Box 32880

Fort Worth TX 76129

227

Treatment and Prevention

Research Issues

Leo E. Hollister

I reflect on these issues from a broad perspective as a clinical pharmacologist

studying various drugs of abuse for more than 30 years, yet with no direct

experience with inhalants. Therefore, I bring that experience to this very

important issue dealing with the prevention and/or treatment of inhalant

abuse.

Inhalants have a great appeal because of certain advantages over other drugs

of abuse. They are widely available and so important commercially that

reducing or controlling supplies has never been seriously proposed. Some are

conveniently packaged, often in ways that appear innocent. The cost for each

intoxication is low, often measured in pennies. The intoxication can be quick

in onset and relatively short-lived, allowing multiple repetitions. Peer group

influence appears to be a stronger factor in promoting inhalant use than with

other drugs.

The study reported by Dr. Simpson is one of the few systematic approaches to

gain some idea of the natural history of inhalant use. Actually, studies of the

long-term course of all drugs of abuse are unusual.

When it comes to long-term evaluations of treatment outcome, the literature

is sparse indeed. Yet such studies are basic requirements for the development

of a strategy aimed at prevention or treatment. One might try to imagine

some of the characteristics of an ideal prevention-treatment program. We

229
should like to identify for such a program youths at high risk for becoming

compulsive users.

Future Directions

The many sociological studies already accomplished, and reinforced by Dr.

Simpson’s findings, suggest various characteristics to identify such persons.

They come from low socioeconomic levels, have many problems with their

families and at school, and associate with drug- or inhalant-using peers.

Using such criteria, one might decide on the characteristics of a preventiontreatment program. It should remove the at-risk person from the proselytizing of peers and the instability of their families. At the same time, it should

try to minimize access to inhalants as well as other drugs. Education would be

important but should be directed at practical goals: vocational training to

prepare the youths for a job and provide some ray of hope in an otherwise

hopeless future. Less important, but included mainly because it is part of

most existing drug treatment programs, would bc education about the potential harm from drugs of abuse. Based on the notion that physical fitness

enthusiasts are the least likely to use drugs, emphasis should be placed on

personal hygiene, athletics, and physical fitness. Efforts should be made to

raise self-esteem, either by the learning of a new skill or by improving physical

development. One might think of many other aspects that could be incorporated into a curriculum.

The word “curriculum,” with its implications of school, was used deliberately.

I would propose that a study be established along the following basis in a

research setting. Inhalant-abusing youngsters should be separated from their

peers and their families by attending a kind of boarding school. One might

think of it as having a character between that of Marine Corps boot camp and

Outward Bound. It might be situated on one of the growing number of

underutilized military bases, which afford enough security to prevent wholesale elopements. The schooling might be of variable length, up to 2 years. If

possible, students should not be returned to their friends and family on discharge but to some semiindependent type of living. These might be the rough

elements of a formal prevention-treatment program.

Assuming that such a program might be feasible to establish, it should be

critically evaluated. Too often in the area of drug abuse, treatment programs

are used without any attempt to assess their worth. It should be possible to

230
make a controlled evaluation by randomly assigning identified at-risk youths

to either the school program or to remain in their present situation. One

would like to follow each group for at least 3 years, using a variety of endpoints of success to compare the two groups. What Dr. Simpson’s study has

shown is that it is possible to follow inhalant users for substantial periods of

time with reasonable degrees of completeness as well as obtain the kinds of

information that would permit a valid assessment of treatment.

Inasmuch as inhalant abuse might be considered, at least for those who use

these substances, as a possible “gateway” drug, such a program of preventiontreatment, were it effective, might be adapted and applied to youths in impoverished areas at risk for becoming cocaine or heroin abusers. The same principles of rehabilitation that might be used for inhalant users might be appropriate for potential users of other drugs.

Such a demonstration project would be expensive, both in terms of dollars

and time. However, the fact that we have the ability to undertake such a study

with available techniques obliges us to try to find what may help this group of

ill-fated youths. We have precious little else to offer.

Conclusions

Followup studies of inhalant abusers have been shown to be feasible for

obtaining the kinds of information that can be used to evaluate a preventiontreatment program. Enough sociological information has been gained over

the years to identify at-risk youths and to define some characteristics of a prevention-treatment program for inhalant abuse. Simple techniques can be

used to establish comparison groups to permit objective assessment of treatment. Such a treatment program for users of one of the earliest used drugs

might provide guidance in the development of similar rehabilitative efforts for

youngsters at risk for cocaine or heroin abuse. The time is propitious for

testing.

231
Author

Leo E. Hollister, M.D.

Professor of Psychiatry and Pharmacology

University of Texas Medical School, Houston

and

Harris County Psychiatric Center

2800 S. MacGregor Way, No. 3A11

Houston, TX 77030

232
Animal Research on

Solvent Abuse

Gordon T. Pryor

Many solvents have been evaluated to establish safe exposure levels and to set

industrial standards. However, in the context of solvent abuse, conclusions

reached from the results of classic toxicologic evaluations may not apply.

Indeed, even in the case of mild to moderate (and sometimes heavy) solvent

abuse, the incidence of verified persisting organ toxicity and/or functional

damage is relatively rare. Moreover, the unambiguous identification of the

agent and/or agents responsible in such cases has been very difficult because

(1) the substances involved are typically mixtures, (2) the formulations and

choices of the mixtures change over time, and (3) the history of the subjects

involved often includes a variety of factors (not the least of which may be the

use of other drugs) that might be partly or primarily responsible for any

observed disorders. Thus, laboratory experiments designed specifically to

address the issue of human solvent abuse are essential if any significant

progress is to be made in our understanding of this phenomenon and its

consequences.

The purpose of this chapter is to review some of the literature and to describe

various toxicological findings from this laboratory on the effects of exposure

of animals to those solvents most commonly found in abused products and

suspected of being involved in the neurologic consequences of heavy solvent

abuse. The discussion will focus on the evidence that implicates specific solvents in relatively severe and persisting neurologic sequelae. The discussion

will be restricted to those solvents found in abused commercial products that

233
are reportedly associated with neurologic dysfunction (anesthetics such as

halothane and the volatile nitrites will not be considered here). Issues of

physicochemical characteristics, pharmacokinetics, and biochemical/neurochemical consequences of the solvents involved, all of which are important in

understanding the mechanisms by which such agents may cause damage to the

nervous system and/or other target organs or tissues, will not be covered (see

Arlien-S borg 1992 for a recent review).

Recognition of the problem of solvent abuse began emerging in the 1960s.

However, aside from scattered case reports and the results of a few isolated

laboratory studies, very little was known about the extent of the problem or

the hazards involved. An important milestone was the monograph by Sharp

and Brehm (1977). This review was especially important because it signaled

the recognition of the problem by the newly formed National Institute on

Drug Abuse (NIDA). Subsequent reviews addressed specific solvents such as

toluene (Benignus 1981a,b), trichloroethylene (Annau 1981),

dichloromethane (Winneke 1981), methyl chloride (Repko 1981), and hexacarbons (Spencer et al. 1980). These reviews often depended heavily on scattered reports from the toxicologic literature, and definitive conclusions were

elusive (see especially Benignus 1981b, p. 413). A more recent discussion of

the problem, including an update of the relevant biologic research (Pryor

1986), was sponsored by the World Health Organization in Mexico City in

1986. By that time some experimental results more relevant to the human

abuse problem were beginning to appear.

In the Sharp and Brehm (1977) monograph the number of solvents and

chemicals that might be considered potentially hazardous in the context of

solvent abuse was relatively large. Since then studies of the solvents of major

concern have focused mainly on toluene and its related analogs xylene and

styrene; dichloromethane (DCM), trichloroethylene (TCEE), 1,1,1-

trichloroethane (TCEA), methyl ethyl ketone (MEK), n-hexane and its

related analogs, and various mixtures containing one or more of these solvents. The major focus in this chapter will be on toluene because of its central role in human solvent abuse.

Acute Behavioral Effects of Exposure to Solvents

Most solvents found in various abused commercial products are CNS

“depressants” at high concentrations and lead to unconsciousness and death

234
with prolonged exposure. However, behavioral manifestations of “excitation”

are seen after short durations of low-level exposure, and during various stages

of emergence after high levels of exposure. On the other hand, a few solvents

such as n-hexane, n-heptane, and some of their analogs (e.g., methyl cyclohexane) often found in commercial products are convulsants at high

concentrations.

The literature describing the acute behavioral effects of various solvents in

animals is not extensive and provides limited insights into the possible persisting neurologic consequences of heavy human solvent abuse that is the

major concern of this chapter. Nevertheless, in reviewing this literature, at

least one broad, albeit unsurprising, generalization emerges. That is, exposure to sufficiently high concentrations of these solvents for sufficient durations of time can markedly affect ongoing behavior and impair performance in

various species of animals, including humans. From the industrial toxicologist’s perspective, this generalization has important ramifications, and the

determination of “threshold” limits for such effects is a goal for establishing

safe exposure standards. From the perspective of solvent abuse, such lower

limits dramatically serve to reemphasize the acute hazards, in terms of potential for accidental injury, that can be associated with this practice.

Having just made this broad generalization, it is just as important to point out

that the behavioral manifestations of acute exposure to various solvents are

not uniform. This point is important for at least three reasons: First, qualitative differences are probably more important in product selection by solvent

abusers than quantitative differences. Second, such qualitative differences

may provide clues as to mechanisms of action that would not be apparent

from differences in potency. Third, classification schemes based on qualitative differences are a necessary step toward understanding the basic structureactivity relationship among various classes of solvents.

An example of the dissimilar pharmacologic effects among various solvents is

provided by the results of some early experiments investigating the effects of a

mixture containing DCM, toluene, commercial heptane (itself a complex mixture), and methanol (Pryor et al. 1977; 1978b; 1980). Acute exposure of rats

to this mixture for 10 minutes caused a concentration/time-related behavioral

syndrome characterized by ataxia, falling, hindlimb flaccid paralysis, sporadic

aimless scratching movements, head jerking, and, finally, prostration and

unconsciousness. When the components were studied alone, the hindlimb

235
flaccid paralysis and head jerking were associated exclusively with exposure to

DCM, whereas the abnormal, aimless scratching was caused by the toluene.

Exposure to the commercial heptanes caused full tonic-clonic seizures that

were subsequently found to have been blocked in the mixture by toluene.

Methanol had only sedative properties, with none of the unusual characteristics noted for the other solvents.

More recently, Rebert et al. (1989a,b,c) examined the acute, concentration/time-related effects of toluene and DCM on the spontaneous electroencephalogram (EEG) and a battery of sensory-evoked responses. Clear and

dramatic differences between the pattern of effects of the two solvents were

observed. Moreover, when the two solvents were combined in various proportions, the results were complex and generally unpredictable from the

results obtained with the separate solvents (Rebert et al. 1990).

These behavioral and electrophysiologic results serve to emphasize the

markedly different pharmacologic characteristics of various solvents, even

though they may all be generally described as CNS depressants. They also

clearly demonstrate that the effects of exposure to a solvent mixture cannot be

predicted simply from the known pharmacology of its components or vice

versa.

Why Solvents?

Various reasons have been proposed to account for why humans use and

abuse psychoactive substances, including inhalants. Whatever the reasons,

the substances selected must have pharmacologic properties that satisfy the

user’s perceived psychologic/psycho-social needs. The actual choice of a substance may depend on diverse and sometimes fortuitous factors, not the least

of which include availability and cost. Because of the complexity of human

psychosocial behavior, identification of the causative use factors and the

properties of the substance(s) involved present formidable difficulties for the

clinical researcher. Fortunately, there are animal models that can be used to

identify the properties of the substances that make them attractive to humans.

Two such models are drug self-administration and drug discrimination. These

models were developed for evaluating the abuse potential of a variety of psychoactive substances, but their application to inhalants has been very limited

thus far.

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Drug Self-Administration

The principle underlying this model is that an animal is permitted to perform

some act (e.g., pressing a lever) to deliver a substance into its body where it

can then exert a “rewarding” effect. This model is a mainstay in the evaluation

of the abuse liability of psychoactive substances such as opiates and

psychomotor stimulants.

Yanagita et al. (1970) first reported that monkeys would self-administer chloroform, toluene, and ether through intranasal cannulae, thus demonstrating

the reinforcing properties of these solvents in animals. This important observation was pursued further by Wood and colleagues who developed inhalation

methods for use in squirrel monkeys (Wood et al. 1977; Wood 1979). They

showed that nitrous oxide and toluene would serve as positive reinforcers,

thus confirming the observation of Yanagita et al. (1970). Other solvents

have not been examined for their abuse potential in this model. A more

extensive examination of a variety of solvents in this model could have important practical applications. For example, if toluene were removed from a

product and another solvent was substituted, it would be unfortunate indeed

if the substitute was as reinforcing, or more so, than toluene itself and/or had

greater toxic consequences. Moreover, this model might be used to find additives that would mask or counteract the reinforcing properties of a solvent

like toluene, either by making the product aversive (see Wood 1979) or by

antagonizing the pharmacologic effect responsible for the target solvent’s

appeal.

Drug Discrimination

This model is based on the principle that chemically induced internal stimuli

can be used to train an animal to make one response (e.g., press a lever) when

the chemical is present and to make another response (press another lever)

when it is not. This model has its roots in the concept of state-dependent

learning (e.g., Overton 1966) and, like the self-administration model, has been

used extensively (Stolerman et al. 1985; 1989 for bibliographies). Its importance is derived from the substitution of a new compound for the compound

used to train the animal. This substitution allows the investigator to determine if the subjective effects of the new compound are similar to or different

from those of the training compound. Thus, in the context of solvent abuse,

this model can be used in animals to explore the extent to which a solvent may

237
have similar subjective effects to those of another solvent or other, perhaps

better understood, psychoactive substances (e.g., opiates, barbiturates, stimulants, alcohol).

Balster and his colleagues have used this model to evaluate the discriminative

stimulus properties of toluene, 1,1,1-trichloroethane (TCEA), halothane,

isoamyl nitrite, and flurothyl and compared them with a number of psychoactive drugs (Rees et al. 1985; 1987a,b,c). They initially trained mice to discriminate pentobarbital from saline. When inhaled toluene was substituted

for the barbiturate, the mice chose the response lever associated with the barbiturate (Rees et al. 1985). They then trained mice to discriminate toluene

(injected) from saline. The cues generalized to toluene (inhaled) and pentobarbital (i.e., these compounds generated similar internal stimuli), but not to

morphine (Rees et al. 1987a). Subsequent results indicated that the pentobarbital cue also generalized to the anesthetic halothane, TCEA, and the

anxiolytic oxazepam, but not to isoamyl nitrite or the convulsant flurothyl

(Rees et al. 1987b). Similarly, mice trained to discriminate ethanol from

saline also generalized to toluene, halothane, TCEA, and oxazepam (Rees et

al. 1987c). More recently, this group reported that rats trained to discriminate ip-injected toluene from saline generalized to methohexital and

oxazepam, but not to chlorpromazine (Knisely et al. 1990).

As a result of these experiments, the authors concluded that inhalants such as

toluene, halothane, and TCEA share some of the discriminative stimulus

properties of other CNS “depressant” drugs. Thus, they suggest that humans

might abuse volatile substances for the same reasons that they abuse other

commonly abused drugs. Moreover, their experiments demonstrate that the

stimulus properties of the inhalants examined are not simply the result of discriminating something from nothing, because generalization did not occur to

other CNS depressants such as morphine and chlorpromazine.

Solvents as Therapeutic Drugs

Reports suggest that some users might inhale solvents to alleviate a perceived

psychologic disturbance by the user. For example, a 14-year-old states that

sniffing toluene relieved a state of chronic anxiety (Press and Done 1967).

Based on such statements, Geller et al. (1983) tested inhaled toluene in a

standard preclinical test in rats designed to identify potential anxiolytic drugs

and compared it with diazepam. Both agents reinstated lever pressing that

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had been suppressed by punishment (i.e., experimentally induced conflict). A

similar anxiolytic effect of toluene was reported by Wood et al. (1984). These

latter investigators also demonstrated that ip-injected toluene and m-xylene

antagonized pentylenetetrazol-induced tonic-hindlimb-extension seizures in

mice and prevented or delayed death. As noted above, we showed that

toluene effectively antagonized seizures caused by exposure to heptanes.

Thus, these results (1) suggest a possible motivation for the use of such solvents by some humans and (2) provide clues as to the acute mechanisms of

action of these solvents. Another potentially interesting report by de

Ceaurriz et al. (1983) indicated that a number of solvents, including toluene,

TCEE, TCEA, xylenes, and styrene, appeared to have antidepressant effects

in mice in a “behavioral despair” swimming test. The interpretation of these

results is difficult because the test is not very specific. Nevertheless, they suggest the need for further study in the context of solvent abuse.

Chronic Effects of Exposure to Solvents

As noted in the introduction, the toxicologic profiles of many of these abused

solvents have been fairly extensive. With few exceptions, the results of these

studies have generally been negative for those organs and tissues examined

and at the doses and routes of administration tested. For example, there was

no evidence of chronic toxicity or oncogenicity in rats exposed up to 300 ppm

toluene for 6 hr/day, 5 days/week, for up to 24 months (Gibson and Hardisty

1983). Results of various studies with xylenes and its separate isomers were

also unremarkable (reviewed by Low et al. 1989). Some evidence for liver

toxicity was reported for DCM in rats (Serota et al. 1986a) and mice (Serota

et al. 1986b), and mild nephrotoxicity was found in male, but not female, rats

exposed chronically to “white spirits” or C10-C11 isoparaffinic hydrocarbons

(Phillips and Egan 1984).

The ability of these industrial toxicologic studies to detect persisting neurologic deficits is questionable. Behavioral, electrophysiologic, and appropriate

neuropathologic measures are rarely included in such studies. Even in those

studies in which neurobehavioral tests have been included, the ability of the

tests to detect specific and/or subtle CNS deficits can be questioned (see the

discussion below). Moreover, the exposure protocols for such studies are

typically not designed to reveal effects more relevant to the human abuse

problem. A particularly striking example is provided by the results of two

studies that examined the effects of exposure for 13 weeks to n-hexane, a

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known neurotoxicant that causes severe peripheral neuropathy (Spencer et al.

1980). In the first study (Cavender et al. 1984), rats were exposed to concentrations up to 10,000 ppm n-hexane for 6 h/day, 5 days/week to simulate a

worst-case occupational exposure regimen. No clinical evidence of neuropathy was observed, and histologic examination of sections of tibial and sciatic

nerves were unrevealing. Only teased nerve preparations showed evidence of

the developing neuropathy. In the second study (Dunnick et al. 1989), mice

were exposed similarly with equally mild consequences. The failure of these

two studies to reveal any but the slightest signs of neuropathy probably can be

accounted for by the pharmacokinetics of n-hexane and the exposure schedules used (as suspected by Cavender et al. 1984 and demonstrated earlier by

Pryor et al. 1982 and Howd et al. 1982). Just as brief, high-level exposures

may not be an appropriate model for the workplace, the toxicologic studies

just mentioned, which were designed to mimic the 5-day workplace environment, may be irrelevant to the excesses seen in substance abuse and cannot be

used to draw conclusions about the potential hazards of a given solvent in the

hands of a dedicated “sniffer.”

Do Solvents Cause Brain Damage?

General concern about the possible toxic effects of chemicals on the nervous

system led to the emergence and development of behavioral toxicology in the

1970s. This concern was motivated to a great extent by the assumption that

the nervous system, because of its complexity and high metabolic demands, is

especially vulnerable to toxic insult, and that behavior, reflecting the integrated output of the nervous system, would be especially sensitive to such insults. These notions were reinforced by Scandinavian investigators who

reported that the main symptoms encountered in workers chronically exposed

to low levels of industrial solvents were psychologic in nature (e.g., fatigue,

attentional disorders, memory problems). Taken together with the scattered

case reports of “brain-damaged” heavy solvent abusers, one might have

expected an explosion of new findings from animal studies demonstrating the

neurotoxic hazards of low-level as well as high-level exposure to solvents.

Few such studies appeared.

In retrospect, some of the reasons seem obvious. First, only a few laboratories worldwide took up the challenge of intensively investigating the possible

persisting neurotoxicity of solvents—chronic inhalation studies are technically difficult, time-consuming, and expensive. Second, the exposure proto240
cols were still geared to the industrial setting and for regulatory purposes.

Third, the test methods used were generally designed for screening purposes

and, as such, could not be expected to detect any but the grossest manifestations of nervous system dysfunction.

Thus, in spite of the increased concern about the potential neurotoxic consequences of solvent exposure, these industrial-type toxicology studies have not

provided much evidence that the solvents encountered in human abuse are

especially hazardous. For example, Kulig (1987, 1989) recently examined

TCEE and styrene in well-designed chronic inhalation studies aimed specifically at detecting neurobehavioral deficits. Although behavioral deficits were

found during the exposure phase, they rapidly returned to normal during the

recovery phase. Even the n-hexane studies cited above would not have identified the severe deficits caused by n-hexane and related solvents in humans

that were well known by then. Because toluene is the solvent most often

associated with reports of neurologic deficits in human solvent abusers, several investigators attempted to demonstrate its neurotoxic effects in animals.

For example, Dyer et al. (1984), using sophisticated electrophysiologic techniques, reported a subtle effect of a 30-day exposure to toluene on the second

of two flash-evoked potentials that might represent an increase in nervous

system excitability. However, the persistence of this effect was not examined.

At about the same time the author and co-workers exposed young rats to high

concentrations (1,400 ppm) of toluene 14 h/day, 7 days/week for 14 weeks

(Pryor et al 1983a). However, using a battery of behavioral and electrophysiologic tests, no convincing evidence for persisting neurologic damage was

found. Interestingly, Naalsund (1986) reported that exposure of rats to

500 ppm toluene (8 or 16 h/day, 5 days/week) for 12 weeks caused a decrease

in the frequency of theta electrical activity recorded from the hippocampus

that was still present 1 month later. However, the reproducibility and functional significance of this effect is still unknown.

The majority of case reports of solvent-induced nervous system damage

and/or disorders have been associated with products containing large amounts

of toluene. This circumstantial evidence led many clinicians to conclude that

toluene, as the common solvent, was the responsible agent. Yet the animal

experiments did not appear to corroborate this conclusion. Also, actual measurement of the contents of the abused products has rarely been reported,

even if they were available for analysis. Therefore, the possibility exists that

some other substance in the products (another solvent or solvents, heavy met241
als, etc.) could, even in small amounts, be responsible. A few reports involving the use of pure toluene (e.g., Grabski 1961; Knox and Nelson 1966) provided stronger evidence to support the assertion that toluene was the responsible agent in the product mixtures. If the human studies were correctly identifying neurotoxic consequences of toluene, then why were they being missed

in the animal studies?

The approaches taken to study the safety of solvents and those used to study

the consequences of solvent abuse are markedly different. The author and his

co-workers have been the only investigators who have maintained a continuing program that has attempted to define the neurotoxicologic consequences

in animals of heavy solvent abuse at the laboratory level. Therefore, the

remainder of this chapter will focus on these studies conducted over the past

13 years.

Some Solvents Are Ototoxic

When these studies began there were very little scientific data on solventinduced neurotoxicities. There was considerable speculation about the solvents being used and their hazards, but mostly, solvents, especially toluene,

were guilty by association. The peripheral neuropathy seen in some industrial

workers and in some solvent abusers had been identified as being caused by nhexane and methyl-n-butyl ketone. Demonstration of the syndrome in animals soon followed, thus opening the way for a systematic investigation of the

mechanisms involved. Therefore, studies in this laboratory began by assuming

that most (if not all) solvents found in abused products were potentially capable of causing irreversible nervous system damage.

Early studies were designed to mimic the human abuse situation, i.e., brief,

repeated exposures to high concentrations. Such exposures might be more

hazardous or have different qualitative consequences than equivalent doses

administered under a low-level, continuous exposure schedule comparable to

those used by industrial toxicologists. A mixture containing dichloromethane

(DCM), toluene, heptanes, methanol, and small amounts of xylenes was

studied initially to mimic abused products. These experiments with weanling

rats employed a battery of behavioral and electrophysiologic tests (Pryor et al.

1983c; Rebert 1983) and provided a large amount of new information about

the acute pharmacologic effects of this mixture, the individual components

thereof, and their interactions (Pryor et al. 1977; 1978a,b; 1980). However,

242
with the exception of n-hexane (Pryor et al. 1982; Rebert et al. 1982; Howd et

al. 1983; Rebert and Sorenson 1983), attempts to demonstrate any progressive

and/or persisting neurotoxicity caused by repeated exposures to the mixture or

the various individual solvents were negative.

In one chronic experiment (Pryor et al. 1983a), exposures to toluene were

sufficient to cause an inhibition of weight gain, a slightly slower acquisition of

a multisensory conditioned avoidance response (MCAR) and a tone-intensity

discrimination, a depression of a component of the brainstem auditoryevoked response (BAER), and a transitory decrease in motor activity during

the exposure phase. However, these changes did not persist after the exposures ended. The slower acquisition of the MCAR was suggestive of a cognitive deficit. However, because the rats were trained during the exposure

phase, residual acute effects could have been responsible. The results of an

experiment with rats trained at various times after the last exposure demonstrated that the deficit was, indeed, transient (Pryor et al. 1983b).

Fortuitously, these rats were not sacrificed at the end of the experiment and

were used in an experiment 2 months later that required them to perform the

MCAR using a 20-kHz tone as the auditory stimulus (instead of the 4-kHz

tone used previously). The tolucne-exposed rats performed the response to

light and footshock stimuli admirably, but they showed a marked deficit in

performance of the auditory MCAR, as though they were unable to hear the

20-kHz tone! Subsequent behavioral and electrophysiologic (Rebert et al.

1983) experiments, in which the intensity and frequency of the tone were varied, confirmed a marked hearing loss at frequencies above 4 kHz. Auditory

dysfunction was also one of the symptoms reported in some workers accidentally exposed to high concentrations of toluene (e.g., Biscaldi et al. 1981) and

in some solvent abusers (e.g., Ehyai and Freeman 1983; Mctrick and Brenner

1982).

These results provided the first clear and indisputable evidence in animals

that exposure to relatively high levels of toluene (e.g., 1,000 ppm) could cause

persisting damage to the nervous system. The results of subsequent experiments (Pryor and Howd 1986; Pryor et al. 1984a,b; 1987) showed that (1)

weanling rats are more sensitive to the effect than young adults; (2) the hearing loss was frequency dependent, being greater at higher than at lower frequencies; (3) damage resulted from loss of receptor (hair) cells in the cochlea;

(4) the effect is concentration, duration, and exposure-schedule dependent;

243
(5) subcutaneous injection of toluene was as effective as inhalation exposure;

and (6) related solvents xylene and styrene also cause hearing loss. However,

this effect is not a common characteristic of solvents (see below). The major

finding of a hearing loss caused by exposure to toluene has been confirmed by

a group in Sweden (e.g., Johnson et al. 1988) and in the United States by

Sullivan et al. (1989), the latter investigators using the oral route of

administration.

A Solvent-Induced Motor Syndrome in Rats

Although the hearing loss associated with exposure to toluene and related

solvents was well established by 1987, neurologic deficits associated with solvent abuse other than hearing loss had not been demonstrated in animals.

Reports continued to appear in which groups of solvent abusers displayed

persisting neurologic symptoms that the clinical investigators attributed to

toluene. Fornazarri et al. (1983) described the symptoms of a group of solvent abusers in Toronto who mainly used a specific brand of contact cement.

The investigators attributed the deficits to toluene. Rosenberg and coworkers

(Hormes et al. 1986; Rosenberg et al. 1988) described similar, but not identical, symptoms associated with abuse of particular brands of paint thinner and

spray paints in Denver that they also attributed to toluene. The Denver reports were especially important because the sample size was relatively large

and the patients studied had been abstinent for at least 4 weeks before examination, a time when residual pharmacologic effects had most likely dissipated.

However, unambiguous assignment of toluene as the causative agent could

not be made since the contact cement from Toronto was found to contain not

only toluene but also hexanes, MEK, and a complex mixture of hydrocarbons.

The spray paint from Denver contained toluene, DCM, xylenes, and propellant gases (recognized by the investigators). Nevertheless, the common, and

major, solvent in both products was toluene. Therefore, toluene was reexamined using tests designed to reflect some of the symptoms reportedly associated with toluene abuse.

Table 1 shows a list of symptoms commonly reported in humans who have

abused various products containing toluene. Some of the symptoms do not

have obvious and measurable counterparts in rats. However, symptoms such

as “wide-based ataxic gait,” “staggering or stumbling in trying to walk,” and

“nystagmus” suggest involvement of sensory-motor systems controlled by the

cerebellum and associated pathways. Therefore, tests were selected that

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Table 1. Signs and symptoms most frequently reported in heavy, long-term

abusers of toluene-containing solvents

Short-term memory loss

Emotional instability

Cognitive impairment

Slurred and “scanning” speech

Wide-based ataxic gait

Staggering or stumbling in trying to walk

Nystagmus

Ocular flutter

Tremor

Optic neuropathy

Unilateral or bilateral hearing loss

Loss of sense of smell

Diffuse slowing of the EEG

Abnormal or absent brainstem auditory-evoked response

Diffuse cerebral, cerebellar, and brainstem atrophy

Enlarged ventricles and widening of cortical sulci,

especially in the frontal or temporal cortex

245
might be reflective of this syndrome in rats. The battery of tests selected consisted of measurements of motor strength (fore- and hindlimb grip [Meyer et

al. 1979]), locomotion (gait analysis [Jolicoeur et al. 1979]), reflexive response

to sudden loss of support [landing hindlimb foot splay (Jolicoeur et al. 1979)],

and sensorimotor balance (rotorod [Christensen 1973]).

Weanling rats were exposed to high concentrations of toluene, n-hexane, or a

mixture of toluene, n-hexane, and MEK 8 h/day, 7 days/week, for 11 weeks

(concentrations ranged from 2,000 to 5,200 ppm). The data were subjected to

discriminant function analysis to identify possible differential syndromes associated with the two solvents and the mixture (figure 1). By 7 weeks there

were clear differences among the groups. These differences were still evident

when the rats were tested 6 weeks after the last exposures.

Examination of the data from the individual tests in the battery showed that

the syndrome associated with exposure to n-hexane was, as expected, mainly

the result of decreased grip strength reflecting the emerging peripheral neuropathy. The syndrome associated with exposure to toluene was characterized

by a shortened stride length and a widened stride width resulting in a marked

increase in stride angle and an increase in landing hindlimb foot splay. The

group exposed to the mixture first took on some of the characteristics of the

group exposed to toluene, but then as the peripheral neuropathy caused by

the n-hexane in the mixture progressed, the effects on grip strength predominated. The rats were also trained and tested for visual, auditory, and

somatosensory sensitivities, and, as expected, the rats exposed to toluene, either alone or in the mixture, had a frequency-dependent hearing loss, whereas

those exposed to n-hexane did not.

The results of this and other experiments (Pryor 1991) provided the first evidence for a persisting motor syndrome in animals caused by exposure to

toluene. Moreover, the syndrome in the rat appeared to resemble the “widebased ataxic gait” described in human solvent abusers. An example of this

effect is shown in figure 2.

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Figure 1. Centroids of groups of rats exposed to toluene, n-hexane, or a

mixture of toluene, n-hexane, and MEK on the first two discriminant

functions derived from the results of a battery of behavioral tests of

motor strength and coordination

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Figure 2. Examples of patterns of locomotion by rats exposed chronically

to toluene. Measurements were made several months after the last exposure

to toluene.

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Other solvents were examined for this syndrome (table 2). Thus far, of the

solvents tested, only xylenes and TCEE have shown a motor syndrome similar

to that of toluene. From the results of this series of experiments, there is now

clear evidence that toluene can cause persisting neurologic dysfunction in

rats, thus confirming its alleged role in human solvent abuse in an animal

model. With such a model it may now be possible to identify toluene’s sites of

action and the mechanisms involved in this effect. Further examination of

other solvents may also give clues about the critical chemical structures

involved as well.

Recommendations

Most, if not all, abused psychoactive substances, including solvents and other

inhalants, may impair performance and/or result in socially unacceptable

behavior because of their acute pharmacologic effects. Compulsive use may

also result in behavior that is morally and legally unacceptable and cause a

progressive deterioration of family, work, and social relationships. However,

the issue of persisting and/or permanent damage to the nervous system

resulting from such abuse has been less clear. Spencer and Schaumburg

(1985) suggested the following criteria for definitively identifying a substance

as the causative agent suspected of being responsible for persisting nervous

system damage in humans:

1. There is a consistent pattern of neurologic dysfunction in humans

associated with well-documented exposure to the substance.

2. The syndrome (all or in part) can be mimicked in animals by appropriate exposure to the substance.

3. Neuropathologic “lesions” can be demonstrated in the nervous system

and/or the peripheral sense organs that satisfactorily account for the

dysfunction in humans and animals.

In their view, and in the author’s as well, “failure to satisfy any of these criteria

leaves room for doubt that the suspect agent is capable of impairing the structure or function of the nervous system” (p. 53). When these investigators

proposed these criteria, they were able to identify only five solvents—carbon

disulfide, n-hexane and methyl n-butyl ketone, toluene (only in terms of

abuse), and impure trichloroethylene—that minimally met their criteria based

249
Table 2. Summary of effects of various solvents on hearing and

motor coordination

Solvent Hearing loss Motor syndrome

Toluene

Xylenes

n-Hexane

Dichloromethane

Methyl ethyl ketone

Trichloroethylene

Trichloroethane

Ethanol

Yes

Yes

No

No

No

Yes

No

No

Yes

Yes

Not toluene-like*

No

No

Yes

No

No

*The peripheral neuropathy caused by n-hexane is different from the motor

syndrome caused by toluene.

on the evidence available. Indeed, their inclusion of toluene in this list was

only possible at that time by our finding of hearing loss in rats associated with

hair cell loss in the cochlea. The case against toluene now has more substance

because of the recent work described briefly above. Nevertheless, considerably more work is needed before we have a comprehensive animal model of

the biomedical consequences of toluene abuse (see table 1).

Although this review focuses on the neurotoxic consequences of solvents in

young animals, an equally important concern is the potential effects of in

utero exposure. This area was not reviewed because so little is known about

solvent abuse in pregnant humans or animals. Preliminary experiments with

toluene suggest that long-lasting motor effects occur in the offspring and are

similar to those described above. Interestingly, no hearing loss has been

observed in prenatally exposed rats, although this effect was evident in the

250
dams. Clearly the issue of in utero exposure to solvents under conditions of

human abuse during pregnancy deserves further attention.

Another area of considerable concern is that of the reported nephrotoxic effects of solvents containing toluene. Although fairly well documented in the

human abuse literature, this issue has received little attention by animal

expcrimentalists. Again, the question of the causative agent (toluene or some

other component of the abused product) can be raised. Although this may be

an acute overdose phenomenon, further work focused on mimicking the

human abuse situation in appropriate animal models will be needed to make

this identification with any confidence.

Finally, as noted above, considerably more work is needed to better define the

characteristics of solvents that make them targets of abuse. Self-administration and drug-discrimination models should be expanded to evaluate a variety

of solvents and their relative abuse potentials. Such models may also offer

opportunities to discover therapeutic measures that might be effective in

counteracting the pharmacologic effects of such solvents that make them

attractive and promote continued abuse.

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Acknowledgments

Research by the author and his colleagues reported in this chapter was supported by NIDA Contract Nos. 271-77-3402, 271-80-3712, and 271-87-3132.

Charles W. Sharp, Ph.D. served as the NIDA project officer.

Author

Gordon T. Pryor, Ph.D.

Neuroscience Department

SRI International

333 Ravenswood Avenue

Menlo Park, CA 94025

258
Basic Science Solvent Abuse

Research Issues

Richard A. Meisch

Pryor’s chapter gives an excellent overview of basic science research findings

concerning inhalant abuse. He also describes his own innovative research

program. Pryor and colleagues pioneered research in this area, and his

description of how this research evolved is very interesting. In fact it is a classic case history of the development of a research program. It is hard to

overemphasize the difficulties encountered when attempting to begin

research in a new area: Essentially no one knows how important variables

should be manipulated and no one knows what measures should be made.

Initial progress is often slow, and results can be discouraging. In spite of these

difficulties, Pryor and his colleagues persisted with their studies, and the

results are very important and form the foundation for future studies.

I want to discuss three aspects of this area of research. The first relates to the

identification of solvent abuse as a member of a larger class of behavior,

namely, drug reinforced behavior. The second suggests some differences in

emphasis on research goals, and the third reemphasizes some of Pryor’s

recommendations.

Solvent Abuse as a Drug Reinforced Behavior

There are a number of views about drug abuse. Often drug abuse is considered to be illegal behavior. If the essential feature of drug abuse is illegal

behavior, then the major approach should be law enforcement. Others con259
sider drug abuse to be immoral behavior, and if drug abuse is primarily

immoral behavior, then a change in the individual’s morals or character would

be an appropriate approach. Others see drug abuse as an outcome of poverty

or stress, and still others view drug abuse as an attempt to self-medicate a disorder such as anxiety. These different views are not simply of academic interest because each view suggests very different ways of conceptualizing and

correcting the problem.

Laboratory research over the past 30 years has led to an interpretation of drug

abuse that differs from the ones I mentioned. This interpretation is that drug

seeking behavior is an instance of operant behavior, and that abused drugs

can function as reinforcers (or less technically as rewards). The basis for this

interpretation is that in laboratory experiments a wide range of animals selfadminister the drugs that humans abuse, and they do not self-administer the

drugs that humans do not abuse.

Food and water often function as reinforcers, and the reasons for this

undoubtedly have to do with evolution. Why do drugs serve as reinforcers?

At present there is no accepted answer to this question. However, it has been

noted that drug reinforcement is a case of a normal biological process, namely

reinforcement, that has by accident gone awry much like an autoimmune

disease is a case of normal biological process that has gone off kilter and

attacked the organism’s own body. This interpretation holds that drug abuse

is a biomedical disorder, and that the appropriate approach is the same as

that in other biomedical disorders, namely, treatment and prevention based

on research in a wide range of disciplines. Such research will lead to an

understanding of etiology and will provide the rational basis for prevention

and treatment. The fact that laboratory animals routinely self-administer

abused drugs, including solvents, indicates that it is ridiculous to characterize

drug taking as simply immoral behavior, since moral concepts are

inappropriate in characterizing the behavior of laboratory animals.

Moreover, it is now unequivocally clear that cigarette smoking is an instance

of drug reinforced behavior, and yet most of us would not characterize

cigarette smoking as immoral. Like certain other chemicals, solvents can

serve as reinforcers for animals, and solvent taking should be considered drug

reinforced behavior.

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Levels of Analysis

Drug abuse is a disorder that occurs at the behavioral level, and it is at this

level that primary analysis should be done. Brains or nervous systems do not

self-administer drugs, and this level of analysis should not be the primary

focus in drug abuse studies. One can have an intact nervous system and still

have disordered behavior. In fact, toxicity at the behavioral level can result

from abnormal functioning of a variety of organ systems.

To understand the determinants of solvent self-administration, one has to

manipulate behavioral variables. Further, to adequately characterize the

adverse effects of solvent abuse, one needs to examine the resulting deficits in

behavior and then relate these deficits to possible organ pathology. It is

interesting that in Pryor’s studies, important progress resulted from careful

consideration of the clinical findings. The point is that the behavior level

should be the primary level of analysis and not the nervous system.

Animal studies of drug self-administration have frequently been described as

models of human drug abuse. I disagree with this view because the animal

studies do not fit the definition of a model: They are not a small-scale replica

or a simulation of something. In animal studies one uses real animals, real

drugs, and obtains real drug reinforced behavior. The animal studies are

more analogous to experimental preparations used in physiology such as the

heart-lung preparation. The use of the term “model” can lead to misunderstandings and to posing the wrong questions. Humans as well as other animals show drug reinforced behavior. The important question is to assess

whether similar variables act in similar ways with both humans and other

animals.

Recommendations

First, the actions of the solvents may have important similarities with the

actions of ethanol and also with those of gaseous anesthetics. Consequently,

research with solvents may have important implications for these other drugs

and vice versa. Second, in biology, genetic effects are pervasive. Such effects

need to be studied with solvents. The use of genetic tools may also be a powerful way to analyze mechanisms of solvent actions.

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I agree with most of Pryor’s recommendations for future research. Among

these are the importance of studying high levels of solvent exposure when

analyzing the consequences of solvent abuse. Pryor has noted that findings

from studies designed to evaluate acceptable exposure levels in industry may

have little relevance for understanding the effects of solvent abuse. He has

also emphasized the importance of looking at qualitative as well as quantitative differences among solvents. Studies are needed with a variety of solvents.

It is important to characterize both similarities as well as differences in the

effects of these agents, and it is also important to study their relation to other

CNS drugs. The characteristics of solvents that lead to their abuse need to be

identified, and more intensive drug self-administration and drug discrimination studies should be conducted. Such studies are necessary for developing

rational treatment and prevention strategies.

Author

Richard A. Meisch, M.D., Ph.D.

University of Texas.

Mental Sciences Institute

1300 Moursund Avenue

Houston, TX 77030

262
Animal Research as a Guide

to Regulation and Prevention

of Solvent Abuse

Ronald W. Wood

Issues of Solvent Dependency

Inhalant abuse is arguably the most toxic of all substance abuse practices.

Consequently, as discussed by several conference participants, biomedical

research has focused on the adverse consequences of this form of substance

abuse, particularly for the nervous and other organ systems. Such work is of

interest not only because of its relevance to inhalant abuse, but also because it

contributes to understanding occupational and environmental health problems, and to a basic understanding of the nervous system and its

pathophysiology.

Identification of the sequelae of inhalant abuse guides one only in the prevention and treatment of organ toxicity; it adds little guidance to prevent the substance abuse practice itself. If society can devise strategies for preventing

inhalant abuse, by definition this will prevent not only solvent-induced organ

system toxicity, but also the displacement of socially productive activities.

Youths sniffing glue are not learning skills or earning money, but are producing behavior impairment that is incompatible with productive activity and

social and intellectual development.

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To devise prevention strategies requires us to address the basic issues of abuse

potential and abuse liability. Abuse potential is that portion of a chemical’s

intrinsic pharmacologic activity, without which there would be no self-administration. Drugs vary in their ability to support self-administration—cocaine

and haloperidol being on opposite ends of this spectrum. The Controlled

Substances Act embodies this relationship between chemical structure and

biological activity in its scheduling process. Abuse liability encompasses both

the pharmacological and extrapharmacologic determinants of the substance

abuse practice; the availability of the substance, its pattern of distribution and

marketing, and social milieus that foster patterns of substance abuse.

Most inhalant products have useful functions in the home and workplace.

Although our society may be able to accomplish a reduction in the abuse of

cocaine by interdiction, we are no more likely to remove from modern life the

volatile chemicals subject to abuse than to give up our dependence on the

motor vehicle. We cannot ban gasoline in order to prevent its abuse.

However, that does not imply that inhalants are beyond regulatory interventions that might reduce both the incidence of inhalant abuse and its toxic

sequelae.

One might hope that the more toxic materials would not be marketed in consumer products and that consumer product formulation might be guided by

the intent to reduce abuse potential. Nonetheless, we still find neurotoxicants

like hexane in some consumer products. “Poppers,” butyl nitrite products,

were sold in this country from 1971 until 1988 as room odorizers even though

they were subject to abuse and smelled like dirty sweat socks (e.g. “Locker

Room, Aroma of Men”) and were toxic (Wood 1988). Despite many deaths

associated with the deliberate inhalation of chlorofluorocarbon propellants,

only the threat of stratospheric ozone depletion resulted in the removal of

chlorofluorocarbon propellants from most commercial products. Thus,

reduction of abuse potential and toxic sequelae through regulation of commercial products has not been foremost on the agenda of the Federal

Government. The difficulties in implementing these types of regulations are

apparent in the public records and hearings associated with regulation of the

volatile nitrites. Eventually, legislation removed alkyl nitrites from the market place. Unfortunately, these products have been replaced with other

“designer nitrites” that apparently fall outside the legislative definition. It

might have been easier to control volatile nitrites if the Consumer Product

Safety Commission had the discretion to weigh the benefits of the product

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against its abuse liability and risk of bodily injury, and the authority to impose

measures ranging from labeling and packaging requirements to an outright

ban of selected product formulations.

The role of scientific research is to improve our basic understanding of the

phenomena and its determinants, so that society may be able to predict and

control the substance abuse practice and its consequences. Although research

agendas are readily drawn, the institutional contexts in which such research

programs can be conducted remain limited. This is a generic problem in neurobehavioral toxicity evaluation, and was discussed in a recent Office of

Technology Assessment report on neurotoxicity (U.S. OTA 1990).

There are few academic environments that consider studies of commercial

product formulations to be an appropriate research activity. An academician

would not study a proprietary volatile polymerizing agent used in the fiberglass industry in order to determine whether or not it is neurotoxic or has

abuse potential. However, if workers have experienced neurotoxic injury by

such a material, (e.g. LUCEL7, trimethyltin, carbon disulfide, methylbutyl

ketone), then a study of the compound might lead to a new understanding of

the structure and function of the nervous system. One should not expect very

much product safety evaluation or toxicity screening to be conducted in the

university context.

Fundamental research can be conducted in universities to further our understanding of (a) why inhalants are subject to abuse; (b) the nature of their

acute and chronic effects; (c) what other drugs of abuse they resemble; (d) the

underlying mechanisms of action; and (e) whether abuse potential and toxicity

can be predicted in advance of distribution, and with what techniques.

Private research institutes and contractors can explore problems of concern to

NIDA, and Pryor’s research program is an example of how the contracting

mechanism can be used productively to focus on questions that would otherwise not be addressed in academic or industrial contexts. In addition, the contracting mechanism should be used to support projects that are sufficiently

challenging or expensive that they will not be undertaken under any other circumstances. Such a project is outlined below in the context of the sequelae of

inhalant abuse.

Finally, the corporate and regulatory sectors have a responsibility to address

these issues as well. Although the Consumer Product Safety Commission and

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the Food and Drug Administration have been able to regulate inhalants when

specific products have led to death (Federal Register Vol. 38, p. 10956, 1973),

these two agencies apparently have limited ability to regulate commercially

available solvents based on inhalant abuse properties. This is principally

because the problem of inhalant abuse has not been interpreted to be within

their jurisdiction or mandate. Perhaps this will change if Congress continues

to express concern about this problem as it did in the Anti-Drug Abuse Acts

of 1986 and 1988. The primary concern of these agencies has been on adequately labeling and packaging products.

Comprehensive premarket toxicity evaluation of commercial chemicals currently falls within the purview of the Environmental Protection Agency

(EPA) under the Toxic Substances Control Act (TSCA). The constrained activities of all of these authorities were discussed in detail in a recent U.S.

OTA report (1990). On July 18, 1981, EPA solicited comment on the need

for testing and appropriate methods for evaluating the abuse potential of an

industrial chemical (Federal Register Vol. 45, pp. 48538-48539, 1980). Later in

1981, EPA prepared a test standard for evaluating the abuse potential of

inhaled substances under the Toxic Substances Control Act. However, as of

now, little useful information has been collected for guiding consumer product formulation or for setting occupational exposure limits for this purpose.

In spite of the magnitude of the challenge to society to cope with this largely

ignored substance abuse problem, the research and testing needs are clear.

The National Research Council’s report on toxicity testing (1984) made it

clear that society is not in a position to perform even a minimal toxicity evaluation of 90 percent of the 50,000-plus chemicals in commerce. Among the

areas to be evaluated, neurotoxicity was among those of highest priority.

Most of the chemicals that are subject to abuse by inhalation fall within the

class of chemicals for which occupational exposure limit values have been

recommended by the American Conference of Governmental Industrial

Hygienists or set by the Occupational Safety and Health Administration. For

approximately 30 percent of these chemicals, the recommended exposure

limits cite the nervous system as the basis for the recommended exposure

limit values. Thus, the adverse effects of volatile chemicals on humans

remains one of the principal sources of information used to prevent subsequent injuries, despite the ready availability of techniques to screen for

adverse effects using laboratory animals. Frequently, studies in laboratory

animals follow the detection of adverse effects in humans, rather than vice

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versa. In this respect, it seems that solvent abusers, who push the dose to

extraordinary levels, serve as a special sentinel population for workers and

consumers exposed to such chemicals.

Approaches to Addressing the Problem

Solvent encephalopathy. No large-scale evaluation of the neurotoxicity of

organic solvents has been undertaken despite several important prompts,

including clear-cut injuries to the nervous system of inhalant abusers, calls for

more work by a consensus conference on solvent neurotoxicity (Cranmer and

Golberg 1986), and a report of the neurotoxicity of automotive emissions and

fuel constituents (Wood 1988b) expressing the need for further solvent neurotoxicity evaluation, the recognition of a psycho-organic syndrome by some

European authorities, and the magnitude in the exposed population. Also,

most laboratory studies evaluating chronic solvent neurotoxicity have not

conformed to the testing guidelines promulgated by EPA and have not

employed the appropriate techniques of modern neuroscience to detect and

quantify the behavioral and neurological consequences of solvent exposure.

Although appropriate first-tier evaluation of solvent neurotoxicity with

rodents would serve to steer the selection of solvent classes for more detailed

evaluation, primates are often the most appropriate subjects for detailed

study. A series of chronic studies should be considered. These could be conducted in two phases. The first phase would identity the hazards by using concentrations and durations of exposure that are maximally tolerated; then a

series of chronic studies using multiple concentrations would provide guidance on the magnitude of the risk. Primates have been recommended for such

studies (Cranmer et al. 1986). Studies should include magnetic resonance

imaging studies, brain stem auditory evoked responses, evaluation of simple

neurological function and conditioned behaviors, and post-mortem quantitative morphometry. The second phase should focus on the sensitive endpoints

demonstrated in the first studies, as well on complex conditioned performances for the assessment of “cognitive” impairments and sensory

dysfunction.

Abuse potential evaluation. Techniques exist for the evaluation of the abuse

potential of inhaled materials (Yanagita et al. 1970; Wood et al. 1977; Wood

1978 1979b; Grubman and Woods 1982). By permitting animals to self-administer solvents one can identify compounds subject to abuse by inhalation.

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These studies also identify the range of concentrations that are effective and

can permit the estimation of relative potency, a matter of particular importance in the context of incidental exposures leading to the discovery of intoxicating effects. Although simple self-administration experiments do identify

the existence of the hazard, they do not permit the evaluation of relative

reinforcing efficacy (i.e., relative risk) from simple rates of response because

of the interactions of direct effects and duration of action of the agents.

Progressive ratio or choice experiments, where animals are permitted to

choose between different concentrations and different agents, are necessary to

evaluate relative efficacy. These are slow and labor intensive experiments that

are of considerable interest and importance.

Characterizing direct effects with schedule-controlled behavior and other techniques. Techniques used for the characterization of the acute effects of psychoactive drugs can be used to further our understanding of the nature of the

effects of inhalants. This strategy relies on using experimental protocols that

have been well characterized with particular drugs of abuse, and evaluating

the effects of inhalants in a similar manner to develop a profile of action.

Using these techniques, some aromatic hydrocarbons have been demonstrated

to be anticonvulsants (Wood et al. 1984) or anxiolytics (Wood et al. 1984;

Geller et al. 1983), while others produce barbiturate like increases in the frequency of conditioned and unconditioned behavior (Wood and Colotla 1990)

and have stimulus properties that resemble barbiturates and anxiolytics (Rees

et al. 1987a,b,c).

Drug discrimination studies have proved to be rapid techniques for characterizing unknowns against reference compounds, and broad surveys of solvent

classes should be encouraged in this area, with an eye to detecting different

patterns of activity. Drug discrimination experiments do not directly address

abuse potential, but address the extent of shared stimulus properties with

such agents. Tolerance is a hallmark of most drugs with abuse potential.

Schedule-controlled operant behavior is appropriate for studying tolerance

and its determinants in the context of inhalants (Rees et al. 1989).

Conditioned stimulus effects related to persistence of substance abuse disorders

and relapse. Stimuli associated with drug administration or within the context

of drug administration can exert powerful control over behavior, both in

increasing its strength, exerting powerful control over tolerance development,

exposing individuals to exaggerated risks associated with administration in

268
unfamiliar environments, and in inducing craving and promoting relapse.

Furthermore, the drugs themselves may exert direct effects on the process by

which conditioned stimuli become effective or exert their control, e.g., effects

on stimulus control or effects on conditioned reinforcing properties.

Irritancy evaluation. Physiological (Kane et al. 1980, Nielsen and Alarie 1982)

and behavioral techniques (Wood 1979a; Wood 1981) are available to characterize the irritant potency of inhalants. The initial irritancy of materials may

correlate well with their abuse potential (Bowman 1977). Several studies

have been performed for related solvents, but major classes have not been

examined. Irritancy increases with lipophilicity within a family of related

solvents.

Structure-activity determinations. The relationship between an inhalant’s

structure, associated physicochemical properties, and its pattern of neurobehavioral activities remains poorly known, despite the passage of a century

since the promulgation of the Meyer-Overton hypothesis (Overton 1901;

Seeman 1972). Systematic research activity of this nature would be of great

benefit because it enables the prediction of relative potency and the identification of unusual activity by a solvent that merits more detailed evaluation.

By its sensitive nature, such work usually must rely on simple assay systems;

nonetheless, work of this nature can also make a significant contribution to

occupational and environmental health. Pharmacokinetic determinations

have been quite limited in this context. Attempts should be made to determine the nature of the disturbances of neuronal and synaptic function associated with solvent exposure.

Complex performances predictive of cognitive, sensory, and intellectual impairment. Techniques suitable for the detection of gross neurobehavioral toxicity

may not detect more subtle impairments produced with chronic exposure.

Therefore, research efforts need to be directed at developing procedures that

can characterize such impairments in detail, as well as techniques that can

detect their occurrence relatively inexpensively in rodents.

Adverse effects on neurobiological development. The fetal alcohol syndrome is

now a recognized entity of great concern. There have been several clinical

anecdotes suggesting the existence of a fetal solvent syndrome. This deserves

further examination to determine if such effects are related to membrane disturbances during development or are attributable to specific compounds or

metabolites.

269
Tolerance, physical dependence, and withdrawal phenomena. The nature of

repeated exposure effects, the extent of tolerance, and its dependence on environmental variables has received only limited attention (e.g., Rees et al.

1989). Withdrawal from solvents has produced only limited evidence of a

withdrawal syndrome, and this may be attributable to the duration of action of

solvents. Ethanol is illustrative of the difficulties associated with producing

sustained nervous system concentrations of inhaled agents. Some solvents

may accumulate with repeated exposure (Rees et al. 1989) and may clear

slowly enough so that withdrawal signs are not expressed. Work with benzodiazepines has indicated that significant dependence potential exists with

compounds that mask their own withdrawal (Lukas and Griffiths 1982).

Comparable phenomena are likely to occur with solvents.

Human studies of direct solvent effects. Cross-species extrapolation is of principal concern for many toxicity evaluations. By its very nature, the study of

potentially neurotoxic chemicals in humans has been quite limited, and has

been restricted to the study of smaller marginal effects. Studies of higher level

exposures characteristic of human solvent abuse have not been undertaken,

but would be of great interest, just as is the study of relatively high doses of

cocaine in human subjects. Attempts might be made to gather more information at high and low levels of exposure to relatively innocuous solvents in

human subjects.

Mechanistic studies. We have little information about the biochemical and

neuropharmacologic consequences of inhalant abuse. In the case of demonstrable ototoxicity, we have little insight into the mechanism of this injury. Is

the injury due to the parent compound or a metabolite? Is the hearing loss

attributable to an acidotic change in the inner ear overcoming the buffering

capacity of the endolymph? Mechanistic studies become of great importance

once the hazards associated with a particular solvent or solvent mixture have

been identified.

Concluding Remark

Substance abuse practices are dependent on a biological substrate of susceptibility to reinforcement by chemicals, a pharmacologic “original sin.”

Focusing on populations that are at risk is of importance because it can identify the familial, social, and cultural factors that predispose to substance

abuse. However, to characterize inhalant abuse as “perverted use” appears to

270
imply a moral or personality defect in the user. Despite the fact that the population at greatest risk is below the age of consent, such stigmatization of the

user works against the effectiveness of therapeutic interventions intended to

promote the adoption of behaviors incompatible with substance abuse and

the reintegration of the user as a useful member of society. Products with

intrinsic toxicities are regulated to minimize injuries, and that regulatory

authority should be extended to minimize inhalant abuse and its toxic

sequelae.

References

Bowman, R.E. Preclinical behavioral toxicology of inhalant solvents. In:

Sharp, C.W., and Brehm, M.L., eds. Review of Inhalants: Euphoria to

Dysfunction. NIDA Research Monograph 15. Rockville, MD: National

Instutute on Drug Abuse, 1977.

Cranmer, J.; Golberg, L.; Brown, T.D.; Gibson, J.E.; and Reiter, L.W.

Neurobehavioral effects of solvents: Proceedings of an international

conference. Neurotoxicology 7(4):1-95, 1986.

Geller, I.; Hartmann, R.J.; Mendez, V.; and Gause, E.M. Toluene inhalation

and anxiolytic activity: Possible synergism with diazepam. Pharmacol

Biochem Behav 19:899-903, 1983.

Grubman J., and Woods, J.H. Schedule-controlled behavior maintained by

nitrous oxide delivery in the rhesus monkey. In: Learning and Memory

Drugs as Reinforcer. Amsterdam: Excerpta Medica, 1982. pp. 259-274.

Kane, L.E.; Dombroske, R.; and Alarie, Y. Evaluation of sensory irritation

from some common industrial solvents. Amer Ind Hyg Assoc J 41:451-

455, 1980.

Lukas, S., and Griffiths, R. Precipitated withdrawal by a benzodiazepine

receptor antagonist (Ro 15-1788) after 7 days of diazepam. Science

217:1161-1163, 1982.

National Research Council. Toxicity Testing. Strategies to Determine Needs and

Priorities. Washington, DC: National Academy Press, 1984.

271
Nielsen, G.D., and Alarie, Y. Sensory irritation, pulmonary irritation, and

respiratory stimulation by airborne benzene and alkylbenzenes:

Prediction of safe industrial exposure levels and correlation with their

thermodynamic properties. Toxicol Appl Pharmacol 65:459-477, 1982.

Overton, E. Studien uber die Norkose Zugleich ein Beitrag zur Allegemeinen

Pharmakologie. Jena, Verlag von Gustav Fisher, 1901.

Rees, D.C.; Knisely, J.S.; Balster, R.L.; Jordan, S.; and Breen, T.J.

Pentobarbital-like discriminative stimulus properties of halothane, 1,1,1-

trichloroethane, isoamyl nitrite, flurothyl and oxazepam in mice. J

Pharmacol Exp Ther 241:507-515, 1987a.

Rees, D.C.; Knisely, J.S.; Breen, T.J.; and Balster, R.L. Toluene, halothane,

1,1,1-trichloroethane, and oxazepam produce ethanol-like discriminative stimulus effects in mice. J Pharmacol Exp Ther 243:931-937, 1987b .

Rees, D.C.; Knisely, J.S.; Jordan, S.; and Balster, R.L. Discriminative stimulus

properties of toluene in the mouse. Toxicol Appl Pharmacol 88:97-104,

1987c.

Rees, D.C.; Wood, R.W.; and Laties, V.G. Evidence of tolerance following

repeated exposure to toluene in the rat. Pharmacol Biochem Behav

32:283-291, 1989.

Seeman, P. The membrane actions of anesthetics and tranquilizers.

Pharmacol Rev 24:583-655, 1972.

U.S. Congress. Office of Technology Assessment. Neurotoxicity. Identifying and

Controlling Poisons of the Nervous System. OTA-BA-436. Washington,

DC: U.S. Govt. Print. Off., 1990. pp. 92-94.

U.S. Government. Air Contaminants; Final Rule. Federal Register

54:(12)2332-2983, 1989.

Wood, R.W. The stimulus properties of inhaled substances. Environ Health

Perspect 26:69-76, 1978.

Wood, R.W. Behavioral evaluation of sensory irritation evoked by ammonia.

Toxicol Appl Pharmacol 50:157-162, 1979a.

272
Wood, R.W. Reinforcing properties of inhaled substances. Neurobehavioral

Toxicology (1 Supp. 1):67-72. Errata: 2, 63, 1979b.

Wood, R.W. Determinants of irritant termination behavior. Toxicol Appl

Pharmacol 61:260-268, 1981.

Wood, R.W. The acute toxicity of nitrite inhalants. In: Haverkos, H., ed.

Extent of Use and Health Hazards of Nitrite Inhalants. National Institute

on Drug Abuse Monograph 83. Rockville, MD: National Institute on

Drug Abuse, 1988a. pp. 28-38.

Wood, R.W. Identifying neurobehavioral effects of automotive emissions and

fuel components. In: Kennedy, D., and Bates, R., eds. Air Pollution, the

Automobile, and Public Health. Washington, DC: National Academy

Press, 1988b. pp. 631-657.

Wood, R.W.; Coleman, J.; Schuler, R.; and Cox, C. Anticonvulsant and

antipunishment effects of toluene. J Pharmacol Exp Ther 230:407-412,

1984.

Wood, R.W., and Colotla, V.A. Biphasic changes in mouse motor activity

during toluene exposure. Fund Appl Toxicol 14:6-14, 1990.

Wood, R.W.; Grubman, J.; and Weiss, B. Nitrous oxide self-administration by

the squirrel monkey. J Pharmacol Exper Ther 202:491-499, 1977.

Wood, R.W., and Weiss, B. Volatile anesthetic self-administration by the

squirrel monkey. In: Sharp, C.W., and Carroll, L.T., eds. Voluntary

Inhalation of Industrial Solvents. Rockville, MD: National Institute on

Drug Abuse, 1978. pp. 355-362.

Yanagita, T.; Takahashi, S.; Ishida, K.; and Funamoto, H. Voluntary inhalation of volatile anesthetics and organic solvents by monkeys. Jpn J Clin

Pharm 1:13-16, 1970.

273
Acknowledgment

Supported by K02-DA00117 and RO1-DA04438 from the National Institute

on Drug Abuse.

Author

Ronald W. Wood, Ph.D.

Research Associate Professor

of Environmental Medicine

New York University Medical Center

550 First Avenue

New York, NY 10016

274
An Industrial/Economic

Perspective of Inhalant Abuse

Robert P. Giovacchini

In 1967, the problem of inhalant abuse and the related health hazards were

abruptly brought to the attention of the industrial world. At that time, the

Federal Trade Commission and the consumer products industry became

aware of seven deaths allegedly involving a consumer product, the “cocktail

chiller.” This product contained only the propellant dichlorodifluoromethane

(Propellant-12). Everyone was, therefore, at a loss to see an association, since

these propellant systems were considered to be “pharmacologically inert.”

This raised the question: Could this propellant or similar propellant systems

be pharmacologically active and cause, at some concentration or set of conditions, death? Three pharmacological concepts developed. They were: (1) the

propellant freezes the larynx, (2) the propellant replaces oxygen in the blood

stream and produces asphyxiation, and (3) the propellant possibly affects cardiac muscle and, more specifically, the cardiac conduction system (Levy 1911,

1912-13, 1913-14).

During this period there were reports in the literature that tended to demonstrate a cause-and-effect relationship with asthmatics and the increased use of

aerosol bronchial dilators (Speizer et al. 1968; Inman and Adelstein 1969;

Gandevia 1968; Scott 1971). Later in 1972, it was demonstrated that the

increased concentration of isoproterenol in the nebulizers marketed in certain countries was positively correlated with increased asthma mortality

(Stolley 1972). But, also during this period, 110 sudden sniffing deaths were

reported allegedly from the abuse of consumer products (Bass 1970).

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Immediately the question was raised: Are aerosol products safe with repeated

use? The Consumer Product Safety Commission held hearings on the subject

of consumer product safety. Sniffing was considered just aberrant behavior

(CPSC 1974). Many parents wanted such products removed from the market

or closely controlled. No one at that time realized the number and types of

products that would be involved if such an approach was taken. Also, the

industry never, at that time, focused on the abuser. Defending the safety of

the products was the issue that had to be resolved.

The Aerosol Inter-Industry Safety Committee was formed, as was a peer

review group of nonindustry scientists to answer these questions (Giovacchini

1972, 1973, 1975). Six studies were commissioned at a cost of nearly $10 million. They included: (1) human exposure to halocarbon gases under controlled conditions (Stewart et al. 1973), (2) animal exposure to halocarbon

gases to examine for possible metabolic byproducts (Blake and Mergner

1974), (3) the effect of fluorocarbon propellants on the cardiac conduction

system of the heart (Flowers et al. 1975), (4) effects of propellant gases on the

upper respiratory system’s defense mechanisms (tracheobronchial mucociliary

clearance) (Bohlen et al. 1975), (5) the effect of propellant gases on the clearance of bacteria from the lungs (Guarneri et al. 1976), and (6) an occupational health study of cosmetologists—a retrospective epidemiology study

(Disher and Hall 1979).

In addition, the Federal Trade Commission had concluded that the “cocktail

chillers” should carry a warning label. Examples of the warning were:

“Warning: use as directed—inhalation of concentrated vapors of this product

is harmful and may cause death,” or “Warning: use only as directed—misuse of

this product by inhaling its concentrated vapors is harmful and may cause

death” (Federal Trade Commission 1969). The cocktail chillers disappeared

from the market over a short period of time.

Labeling was proposed by the Food and Drug Administration and also by the

industry. It was believed that this would alert parents. But others argued that

this approach would also identify, for the sniffer, those products that would

give them a high. The FDA proposed label stated, “Do not inhale directly;

deliberate inhalation of contents can cause death” (Food and Drug

Administration 1973).

The proposed industry label stated, “Use only as directed; intentional misuse

by deliberately concentrating and inhaling the contents can be harmful or

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fatal.” The industry label was approved by the FDA (Food and Drug

Administration 1975).

During this period, the consumer products industry became aware of deterrents. The sniffing of hobby cements during the 1950s had apparently been

deterred by the addition of oil of mustard to the product. The use of deterrents had been mentioned by both regulatory and industry scientists. Here

was a situation where apparently a deterrent (a known approved food additive) appeared to work, at least in some individuals.

Several hundred chemicals were reviewed for their olfactory abilities to create

tearing, malodor, or nausea. None were really examined for any length of

time because many were either too toxic, unstable, or not effective enough.

Some companies tried to add oil of mustard to their products, where marketing of the products with deterrent was not a problem. But the majority of

companies could not or did not add a deterrent to their products. Rather,

they labeled the products.

During this period, a group from industry founded and financed the Aerosol

Education Bureau (Aerosol Education Bureau 1970, 1984). This industry

group was organized to disseminate information on aerosols to the science

departments of schools. It was believed at that time that the incidence of

sniffing would be reduced once a youngster recognized the hazards associated

with this form of aberrant behavior. We do not know what effect this educational program had, but we do know that many teachers and parents first became aware of “sniffing” through this medium (Aerosol Education Bureau

1984). Several companies also hired film companies to make movies on

sniffing and the detrimental effects it could have on the body. These films

were never released. At the time, experts believed that the films would not

deter sniffing and, in fact, might cause more youngsters to experiment with

chemicals, using this technique.

Interestingly, during this period, sales of aerosol products did not drop. The

consumer was satisfied with the products, and sniffing was seen as something

done by a very small fraction of youngsters who were on the “fringe.”

Legislation tried to deal with the symptoms of the problem. Was it product

based, abuser based, or supply based? To deal with the product, companies

used warning labels, deterrents, repackaging, and reformulation. Legislation

attempted to remedy the abuser-based issue by making it: illegal to sniff, ille277
gal to purchase to sniff, illegal to be “high” from sniffing, and a treatable offense (through referral to drug treatment centers) if caught sniffing. In regard

to the supply-based aspect of the problem, legislation was introduced and

included limitations on the purchase of these products by minors, on the sales

of certain products to minors for sniffing purposes, and on any sales of

selected products.

From the viewpoint of the consumer products companies, the period of the

later 1970s saw an end, or at least a great drop, in the abuse of their products.

Many of us believed that the labeling of the product and the education of

teachers and parents had caused the problem to retrogress. It was not until

the early 1980s that we realized that the problem had not gone away. The

abusers had found other legitimate products that they were now sniffing. The

industry also found out that what was originally thought to be a U.S., and to

some extent a Canadian problem, was, in fact, a worldwide problem. At that

time most scientists and regulators believed the problem of sniffing should

not be brought to public attention so as not to escalate the issue.

After years of working pro bono (most companies assigned one or two people

to work on this problem), we seemed to be nowhere. But several facts had

become clear: Every solvent had the ability to produce untoward effects when

inhaled under perverted conditions, and it would be impossible to remove all

products from the marketplace that could give a high. What was the answer?

Well, it was not a question of product safety. Industry had to focus on the

abuser. We had to focus on the social problem. Why would someone want to

get a high by sniffing legitimate commercially available consumer products?

But our problem is much larger than just legitimate consumer products. Our

problem is substance abuse, which is a worldwide social problem. The issue,

then, is one of people, not one of product. When the industry first realized

this in the late 1970s and early 1980s, we began to re-review our entire program and where it should be headed. This was necessary if industry was to

meaningfully help in attacking the problem.

The world of the 1960s and 1970s was different from the world of the 1980s

and 1990s. We are today facing a serious substance abuse problem that is

attacking the very marrow of the country and the world.

Thus, while many years had been spent defending the safety of consumer

products before various regulatory bodies, hindsight now demonstrates that if

278
that time and money had been spent on the societal issue, we might well be

further ahead in dealing with this problem. The questions are: How do you

stop destructive behavior? What causes destructive behavior? How do you

turn that around? Why sniffing? Why not sniffing? How does all this relate

to the abuse of either legal or illegal substances?

When I first became involved with the “sniffing” problem in 1968, the youngsters were of high school age. Today, younger individuals in the sixth and seventh grades are inhaling substances to get high, and high school age youths

are using other substances as well as inhalants. It has been suggested that solvent abuse is the “gateway,” implying that this is the highway to illegal substances. Further complicating the issue is the number of students that drop

out of school. How does this reflect on the interpretation of the levels of substance abuse measured? Also, is there a relationship between dropouts and

drug abuse?

Many have studied sniffers (Giovacchini 1985). What are their characteristics? The picture we see is one of high unemployment levels among parents,

absent parents, single parent families, and belonging to a large family at the

low end of the social economic scale. But sniffers are different from other

drug users. They are often younger, more likely to be delinquent and disruptive, and usually in conflict with the justice system because of some delinquent

or disruptive behavior. They have very low self-esteem and have a lack of

motivation. They do poorly academically and have a higher than normal

school dropout rate. They tend to come from minority low income families

with all the attendant serious problems.

However, I believe that we also see the problem in middle and higher income

families. I believe the real issue is not income, but rather the youngsters’ perception of whether or not the future is worth fighting for. Do they have a

chance of getting out of their present social situation? Where is the help that

will give them the tools and the support to supply them with the necessary

accouterments to develop positive, instead of destructive, goals—i.e., a plan

and pathway to change their future? Is the problem that they have no one to

turn to as guides to the development of the correct skills? If this is true, then

they see no answer to their problems, and it is no wonder they get high,

because they have to feel there is no future for them. Does this have anything

to do with the increased teenage suicide rate?

279
The Federal Government has spent billions of dollars to fight substance

abuse. There are basically two programs, one dealing with supply reduction

(interdiction—about 70 percent of the funds) and the other with demand

reduction (about 30 percent of the funds) (Bush 1990). The major feature of

the demand reduction program is treatment and prevention. We seem to be

recognizing that substance abuse is causing societal changes and that educational and community action programs are necessary. But the focus again is

on illegal drugs, and less on the “perverted use” of legitimate products. While

no one can disagree with approaches to deter and change illegal drug user

attitudes, it is conceivable that the illegal drug user differs from the “sniffer”

and that different approaches to prevention may be required (Mason 1979).

It has been stated that substance abuse has cost society $60 billion, $33 billion

of which is due to lack of unrealized productivity (Mulcahy 1989). Others

claim that substance abuse costs the business community as much as $100 billion annually through increased absenteeism, added health care costs, and

accident rates that are 10 times higher for abusers than for nonabusers (Bacon

1989). The amount of money spent for mental health care appears to have

risen from $34 billion in 1984 to about $70 billion in 1987 (Howard 1989). In

a survey conducted by Marsh and McLennan Co., the conclusion was reached

that substance abuse in the workplace costs employers from 1 percent to 5

percent of their payroll each year, and further, the annual cost of substance

abuse to business and to State and local government is between $60 and 65

billion (Kiltrell 1989). It has been estimated that 17 million people in the

United States have a substance abuse problem that is serious enough to warrant professional help and that if left untreated the insurance claims will cost

nearly $48 billion annually (Carels 1987). Alcoholism costs industry over $25

billion annually, and workers who smoke cost the employer $624 billion more

in annual medical costs (Williams 1986).

How much of these costs can we attribute to sniffing? I do not know, but I am

guessing that very little of these costs are directly caused by sniffing. What we

are seeing are the costs, in industry, basically due to alcohol abuse and illegal

substance use. While there have been reports in the literature of adult solvent

abuse, most of the literature suggests that solvent abuse is a problem in the

young (Hershey and Miller 1982). Therefore, what are the costs of solvent

abuse in industry? We do not know.

280
What are the costs to the Nation of solvent abuse? Why do we talk about

employee assistance programs (EAPs) in industry to help the employee solve

his or her problems, but do very little to provide programs to help the youngster? In 1985, it was reported that the costs of EAP programs, supplied by

outsider contractors contracted on an annual per capita basis, ranged from

$10 to $60 per employee per year. Further, keep in mind that such industry

programs deal with more than alcohol and substance abuse. Industry has recognized that only about half of the employee problems are due to substance

abuse (MacDonald 1985).

What are the costs to the Nation of solvent abuse in youngsters? Industry

cannot give you this figure readily. Possibly insurance companies can give us

an estimate based on the numbers and cost of incidences of alcohol, drug

abuse, and mental illness (ADM) in dependents of employees. But, more

than today’s financial costs, what are we going to do with these youngsters

when they become adults? How will they interact with society? If we allow

this destructive behavior to continue throughout their childhood, what will

they contribute to society as adults? There is the argument that we need more

money for treatment centers and that treatment centers have been underfunded—and that is why there are so many nontreated substance abusers.

That may be true, but that is not the total answer. Neither is the shortsighted

answer that many officials give—that is, we must keep these kinds of products

out of the hands of youngsters, the semi-interdiction approach.

We have to have sufficient treatment centers; there is no doubt about that.

But, more important, we must have community education programs that give

the tools to turn destructive behavior of children into positive behavior. If

industry can have Employee Assistance Programs, then maybe communities

can have Community Assistance Programs for youngsters in school in their

formative years. The industry has supported the development of the Solvent

Abuse Foundation for Education (SAFE) particularly aimed at reducing solvent abuse. A greater cooperation of the communities and industry can lead

to even greater strides in resolving this problem in our youths. In this way

local people can help solve local problems. The previously mentioned industry-supported programs are built to utilize the community as the active force

working with youngsters to give them the support and proper goal setting to

face today’s challenges and crises. If something is not done now, the financial

costs we will be reporting in the future will not only be higher, but industry

will have a reduced pool of individuals available for employment. But the

281
bigger problem is, what impact will this have on the Nation if no changes are

undertaken?

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Stolley, P. Asthma mortality. Am Rev Resp Dis 105:883, 1972.

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Administrator 31(12):68-76, Dec. 1986.

284
Author

Robert P. Giovacchini, Ph.D.

Vice President, Corporate Product Integrity

The Gillette Company

401 Professional Drive

Gaithersburg, MD 20879

and

Chairman

Solvent Abuse Foundation For Education (SAFE)

Suite 250

750 17th Street, N.W.

Washington, DC 20006

285

Development of

Alternative Fluorocarbons

Henry J. Trochimowicz

Introduction

Chlorofluorocarbons (CFCs) have been used as refrigerants, solvents, aerosol

propellants and foam blowing agents over the past 50 years. Selected physical/chemical properties and uses of common, commercial CFCs are shown in

table 1.

The main reasons for their wide acceptance in these uses were chemical stability, low toxicity, and a lack of environmental reactivity. However, CFCs

appear to have one serious problem—an environmental stability in the lower

atmosphere resulting in subsequent breakdown in the upper atmosphere,

leading to ozone depletion. Suggested requirements for CFC replacements

are shown in table 2.

Therefore, industry needs to create chemicals that are “less environmentally

stable,” and therefore more environmentally acceptable: with low ozone

depletion potential, low global warming potential, and a low photochemical

reactivity. These chemicals should still possess, however, a high degree of

chemical stability in their end uses and be relatively low in toxicity. As these

alternative fluorocarbons are introduced into the marketplace, it is important

that deliberate abuse of these new chemicals does not occur. Manufacturers

need to educate their workers and customers, but also they need to work

through interindustry groups to teach parents, teachers and youngsters about

287
Table 1. Chlorofluorocarbons—properties and applications

CFC Chemical B. pt.

No. formula °C

Vap. press.

Bar A/25°C

Principal

applications

113 CCl2FCClF2 47.6 0.45 Solvent, chemical

intermediate

11 CCl 3F 23.8 1.07 Aerosols, foams,

solvents

114 CClF2CClF2 3.8 2.18 Aerosols, foams,

refrigerants

12 CCl 2F2

-29.8 6.57 Aerosols, foams,

refrigerants

115 CClF2CF3-38.7 9.09 Refrigerants

Table 2. Requirements for alternatives to CFCs

Environmentally acceptable

- Low ozone depletion, low global warming potential, and negligible

photochemical reactivity

Low toxicity to humans and other life forms

Non- or low flammability in products or other end uses

Commercially applicable

Commercially acceptable properties for end use applications

Cost effective

288
the hazards of inhalant abuse. The education process starts with a knowledge

of what the new CFC alternatives are and some information about their toxicity potential. This information is summarized in the subsequent tables.

Fluorocarbons in general have different properties and different applications.

Therefore, when one looks for replacements, a good starting point is a comparison of the physical properties of old versus the new type of fluorocarbon

(see table 3). Some alternatives that are already available, along with their

uses, are listed in table 4. Selected chemical and physical properties of these

compounds are listed in table 5 and a brief summary of their toxicities is

shown in table 6.

There are several other chemicals under development as replacements for

CFCs. These compounds, their uses and selected chemical and physical properties are listed in tables 7 and 8. On a worldwide basis, fluorocarbon producers have sponsored a cooperative program to expedite the acquisition of toxicology data on these compounds. It is called the Program for Alternative

Fluorocarbon Toxicity Testing (PAFTT). The companies are: Akzo, ICI,

Allied-Signal, Rhone-Poulenc, Asahi Glass, Kali Chemie/Solvay, Atochem,

Montefluos, Daikin, Pennwalt, Du Pont, Hoechst, Showa-Denko, and Ulsan

Chemicals. A testing profile proposed for these new alternatives is summarized in table 9. Currently, over 50 tests are underway or are completed. The

goal is to complete these tests in about 5 years. The progress to date for compounds HCFC-123, HFC-134A, HCFC-141B, HCFC-124 and HFC-125 is

noted in tables 10, 11, 12, and 13.

A comparative toxicity profile for CFC-11 and HCFC-123 is shown in table

14. In general, the HCFC replacement is of equal or lower toxicity. Similar

findings were obtained for another alternative, HFC-134A, when compared to

CFC-12 in table 15.

It appears from research to date that the replacement compounds (HCFCs)

for the previously used aerosol propellants (or CFCs) will not only be better

for the environment but will have a relatively low order of toxicity.

Relative to inhalant abuse in particular, the chemical industry will take the

following actions:

1. Continue the development of low toxicity alternatives for CFC solvents, propellants, refrigerants, and blowing agents.

289
Table 3. CFCs and alternatives

Currently used CFCs Alternatives

Formula CFC No. Boiling Point FC No. Formula

CCl2F.CClF2 113 47.6

32.0 141B CH3CCl2F

27.8 123 CHCl2.CF3

CCl 3F 11 23.8

CClF2.CClF2 114 3.8

-9.2 142B CH3.CClF2

-12 124 CHClF.CF3

-24.5 152A CH3CHF2

-25.0 DME CH3OCH3

-26.5 134A CH2F.CF3

CCl 2F2 12 -29.8

CClF2.CF3 115 -38.7

-40.8 22 CHClF2

-49 125 CHF2.CF3

Table 4. Principal alternatives to CFCs (commercially available)

Dimethyl ether (DME)—Propellant

HCFC-22—Air conditioning agent, refrigerant, blowing

agent, propellant

HCFC-142b—Blowing agent, refrigerant blend component,

propellant

HFC-152a—Refrigerant blend component, blowing agent,

propellant

290
Table 5. Properties of commercially available alternatives

HCFC-22 DME HFC-152A HCFC-142b

Formula CHClF2

B. Pt. (°F) -41

V.P. (psig)

70 °F 121

Ozone Depletion

Potential (ODP)

(vs. CFC-11 = 1) .05

Global Warming

Potential (GWP)

(vs. CO2 = 1) .34

Volatile Organic

Compound (VOC) No

Flammable No

Workplace

Exposure Limit 1,000

(ppm by vol.) TLV

CH3OCH3 CH3CHF2 CH3CClF2

-13 -13 +14

63 63 29

0 0

Negl .03 .36

Yes No

Yes Yes

1,000 1,000

AEL AEL

.06

No

Yes

1,000

AEL

Toxicity testing

TLV = Threshold Limit Value proposed by the American Conference of

Governmental Industrial Hygienists (ACGIH)

AEL = Acceptable Exposure Limit proposed by the Du Pont Company

291
Table 6. Toxicological summary of commercially available alternatives

(DME, HCFC-22, HFC-152a, HCFC-142b)

Low order of acute and chronic inhalation toxicity

Weak cardiac sensitizers

Low order of skin and eye irritation/sensitization

Pose no hazard to humans from the viewpoint of systemic toxicity,

carcinogenicity, mutagenicity, or teratogenicity when used within their

TLVs or Du Pont AELs

TLV = Threshold Limit Value proposed by the American Conference of

Governmental Industrial Hygienists (ACGIH)

AEL = Acceptable Exposure Limit proposed by the Du Pont Company

Table 7. Principal alternatives to CFCs

(not commercially available)

HCFC-123 AND HCFC-141b

Principal candidates for replacing CFC-11 in blowing agent applications

HCFC-124

Potential candidate for specific blowing agent, refrigerant uses

HFC-125

Potential candidate for air conditioning, refrigerant uses

HFC-134a

Potential candidate for CFC-12 in refrigeration applications

292
Table 8. Properties of noncommercially available alternatives

HFC-125 HFC-134A HCFC-124 HCFC-123HCFC-141B

Formula CF3CHF2 CF3CH2F CF3CHClF CF3CHCl2 CH3CCl2F

B. Pt. (°F) -55

V.P. (psig)

70 °F 165

Ozone Depletion

Potential (ODP)

(vs. CFC-11 = 1) 0

Global Warming

Potential (GWP)

(vs. CO2 = 1) 0.84

Volatile Organic

Compound (VOC) No

— —

Flammable

Workplace

exposure

(ppm by vol.)

No

1,000

AEL

-16

70

0

0.28

No No

No No

1,000

AEL

+12

33

0.02

0.1

500

AEL

+82 +90

0.02 0.15

0.02 0.15

No No

No Yes

10 500

AEL AEL

Toxicity testing

PAFTT = Program for Alternative Fluorocarbon Toxicity Testing

AEL = Acceptable Exposure Limit proposed by The Du Pont Company

293
Table 9. PAFTT proposed toxicity testing schedule

Phase I (6-8 months)

Acute inhalation (LC50, ALC)

Dermal and eye irritation/sensitization

Dermal toxicity (LD50 in 2 species)

Cardiac sensitization

Genotoxicity (AMES, lymphocyte, micronucleus)

Other (acute oral, human patch studies)

Phase IIa (6-8 months)

Subacute inhalation (4 weeks)

Preliminary pharmacokinetics (blood levels, uptake, elimination)

Teratology probes (2 species)

Environmental toxicity

Phase IIb (1 year)

Teratology (2 species)

Phase III (1 year)

90-day inhalation

Metabolism—CNS effects

Phase IV (4 years)

Chronic inhalation toxicity/carcinogenic study

PAFTT = Program for Alternative Fluorocarbon Toxicity Testing

294
Table 10. Present toxicity testing status on HCFC-123

Low in toxicity on an acute basis

Not mutagenic—based on in vitro and in vivo studies

Not a developmental toxin—in rats or rabbits

Low in toxicity on a subchronic basis

Chronic inhalation toxicity study in rats—after 24 months exposure

- Initiated 1/89 (doses of 0, 300, 1,000, and 5,000 ppm)

- No adverse effect on survival

- Liver weight (slight decrease)

- Peroxisome proliferation (slight increase)

- Triglyceride, cholesterol, and glucose (levels decrease)

- Higher incidence of benign liver, pancreatic, and testes tumors

Table 11. Present toxicity testing status on HFC-134A

A gas of low order of toxicity (acute and repeated exposure)

Practically not metabolized; not accumulated; quickly eliminated

Nongenotoxic

Not a developmental toxic in rats or rabbits

Inhalation

- Subchronic low toxicity

- Carcinogenic/chronic toxicity study in rat is in progress (initiated 10/89)

295
Table 12. Present toxicity testing status on HCFC-141B

Not mutagenic or clastogenic

Negligible acute toxicity/irritation potential

Reversible anesthetic effects

Low order of subchronic toxicity

Not a developmental toxin in rats or rabbits

Chronic toxicitykarcinogenicity study in rats in progress (initiated 1/90)

Table 13. Present toxicity testing status on HCFC-124 and HFC-125

HCFC-124

Very low order of acute and subchronic toxicity

Minimal CNS effects at 50,000 ppm

Moderate cardiac sensitization potential

Not mutagenic (in vitro or in vivo)

Not a developmental toxin

Chronic study—to be initiated in 1992

HFC-125

Low order of acute inhalation toxicity

Not mutagenic

Subchronic inhalation toxicity studies in progress

296
Table 14. Comparative toxicity of CFC-11 and HCFC-123

CFC-11 HCFC-123

Formula

Boiling point

4-hr LC50 (Rats)

10-min EC50 (CNS, Mice)

AMES (Salmonella)

In vivo genotoxicity (rats)

Cardiac sensitization

threshold (dogs; epi i.p.)

Subchronic noel (rats)

Teratology (rats)

Teratology (rabbits)

Carcinogenicity (oral, rats)

Carcinogenicity (inhal., rats)

Metabolism (

14C-label, rats)

Occupational limits

CFC13

23.7°C

26,200 ppm

35,000 ppm

Negative

5,000 ppm

5,000 ppm

Neg. at 20,000 ppm

Negative

Neg. at 5,000 ppm

Not metabolized

TLV = 1,000 PPM C

AEL = 1,000 PPM

TWA

CF3CHCl2

27.1°C

36,000 ppm

<40,000 ppm

Negative

Negative

> 10,000 ppm

1,000 ppm

Neg. at 10,000 ppm

Neg. at 5,000 ppm

Produces benign tumors

of the liver, pancreas,

and testes

Slight metabolism

TLV - NONE

AEL = 10 PPM

(8-hr TWA)

(TVL= Threshold Limit Value [ACGIH]; AEL = Acceptable Exposure

Limit [Du Pont Company].)

297
Table 15. Comparative toxicity of CFC-12 and HFC-134A

CFC-12 HFC-134A

Formula CCl 2F2 H2CFCF3

4-hr LC50 (rats) 760,000 ppm 500,000 ppm

AMES (Salmonella) Negative Negative

In vivo genotoxicity (rats) Negative Negative

Cardiac sensitization

threshold (dogs) 50,000 ppm 75,000 ppm

Subchronic noel (rats) 10,000 ppm 50,000 ppm

Teratology (rats) Negative Negative

Carcinogenicity (oral, rats) Negative Negative

Metabolism (

14C-label, rats) None None

Occupational limits 1,000 ppm (TLV) 1,000 ppm (AEL)

(TVL = Threshold Limit Value [ACGIH]; AEL = Acceptable Exposure

Limit [Du Pont Company].)

298
2. Utilize, at all times, the most effective warning language on labels, on

material safety data sheets, and in product literature.

3. Continue to support, on an individual company basis and through

interindustry efforts, education programs on the potential hazards of

inhalant abuse for:

our own workers

our customers

parents, teachers, and young people at the earliest possible age

Author

Henry J. Trochimowicz, Sc.D.

Staff Toxicologist

Du Pont Company

Haskell Laboratory for Toxicology

and Industrial Medicine

Newark, DE 19711

299

Recommendations

The focus of the conference was to establish future areas of research worthy of

support and necessary to accomplish the goal of a reduction in inhalant abuse,

especially among young people. In preparing this set of recommendations,

several specific as well as broader recommendations, which seem to be manageable research endeavors, have been identified and organized in this section

according to the appropriate fields of research. The knowledge gained from

new research identified by these recommendations should provide us with the

needed elements to more successfully attack the inhalant abuse problem.

General Considerations

One issue was extensively discussed but not resolved. There is a need in the

field for clearer definitions of the solvent-inhalants abuse area. At a minimum, greater differential clarity is needed between (a) solvents, (b) medicinal

anesthetics, and (c) the nitrites. This is not only a problem for epidemiologists evaluating the extent of use but also for many clinical researchers. In addition, there are several recommendations that should be considered for future clinical and/or epidemiological studies. These are outlined here prior to

the listing of more specific recommendations for research.

I. Case Studies

A . Investigators need to conduct more complete and accurate histories of

drug/inhalant exposure; measure urine/blood/tissue levels where possible and apply other techniques to determine extent of exposure.

B. Researchers need to screen individuals for acute toxicity before being

evaluated so acute intoxication can be differentiated from long-term

301
or chronic irreversible changes. Toxicity (medical or psychological)

studies on humans should be conducted several days to weeks after the

subject has been abstinent from inhalant use.

C. Future toxicity studies should utilize the most recent and sophisticated techniques to assess toxicity (especially neurotoxicity) of existing

as well as newly introduced solvents and propellants. Establishment

of the initial MRI parameters and other standardizations are essential

for cross-study comparisons.

D. Researchers should perform independent chemical analyses of the

compounds under study. Manufacturers’ product ingredient labels are

often incomplete for these complex compounds.

II. Case and Cohort Studies

E. Studies of minority and ethnic populations should be careful in distinguishing differences and unique characteristics among each of these

groups. For example, in studies of Hispanic populations, differentiations should be made between Mexican Americans, Spanish

Americans, Cuban Americans, Puerto Rican Americans, and other

Latinos from Central and South America. As for any ethnographic

study, detailed definitions for subgroups within an ethnic/minority

group are needed.

F. Special attention must be paid to the role of mediator variables in

studies of the etiology of inhalant use behaviors. Consideration of

socioeconomic, political, or other population variables in different

locales are important in discerning possible mediator variables and

their effects.

G. In light of the low base rate of inhalant use compared to other drug

use, special attention should be paid to inclusion of inhalant questions

on general drug surveys. Many research endeavors fail to incorporate

inhalant-specific components in their research protocols.

H. Standardization of solvent questions on surveys is much needed. For

example, both the NIDA National Household Survey and the High

School Senior Survey could disaggregate their overly inclusive ques302
tions on inhalants. At a minimum, volatile solvents must be clearly

distinguished from nitrites. It is suggested that the appropriate agencies convene a panel of experts to aid in standardization.

I. It is important to obtain detailed histories of all the types of solvents

and drugs used—not just the street names or other jargon—and an

adequate description of the amounts used per episode and over time.

J. Special attention to cohort effects as well as historical trends is

essential.

The following identify some specific areas of solvent, or other inhalant, abuse

research identified by the participants as important to conduct.

General Studies

1 .

2.

3.

Long-term followup studies of users should be a prime focus. These

studies are relevant to epidemiology, treatment, prevention, drug

effects research, and outcome.

The development of comprehensive data systems can be useful repositories of inhalant abuse information.

Given the similarities of alcohol and toluene (and other solvents)

actions, studies are needed on the incidence of alcohol use among solvent abusers, and a measure taken of the synergistic effects of alcohol

and solvents (like toluene) when used together. Alcohol abuse may be

a confounding cofactor in resolving solvent abuse questions and

problems.

Pharmacologic and Toxicologic Studies (Animal)

4. There should be a variety of studies in different species evaluating the

long-term cognitive outcome effects of prolonged solvent abuse.

5. Studies on the pharmacodynamics, distribution, and bioavailability of

toluene and other abused solvents and their metabolites need to be

303
6.

7.

8 .

9.

10.

investigated to be able to compare the effects in experimental animals

with those in humans.

Drug interaction studies (of different solvents as well as solvents and

other drugs) are needed in light of the fact that inhalation of combinations of solvents is typical in occupational as well as drug abuse

settings.

Several different acute and chronic neurotoxic studies concentrating

on subhuman primate species as well as other animal models should

be conducted. These studies should unambiguously identify the solvent and/or solvents responsible for specific toxic effects.

Drug-discrimination studies are needed to compare subjective (user

experienced) effects across a range of abusable drugs and solvents.

Such data can shed light on whether humans abuse volatile solvents

for the same reasons they abuse other, noninhalant drugs. If so, can

one predict which new “solvents” the user might select and any alternative use of drugs when inhalants are less desirable.

The issue of in utero exposure to solvents under conditions of human

abuse during pregnancy (fetal toxicity) deserves further attention and

study. It is becoming more apparent that toxic effects occur in

neonates born of mothers who used inhalants while pregnant.

Experimental animal and retrospective human studies should be

conducted.

Studies to determine if alternatives for CFC solvents

(chlorofluorocarbons), propellants, refrigerants, and blowing agents

have suitably diminished toxicities.

Clinical Case and Cohort Studies

11. Cross-sectional and longitudinal studies on the problems associated

with human use of inhalants in natural settings are needed. Such

studies should collect information on the effects of dose, duration of

exposure, analysis of the solvent mixtures, users’ nutritional status, use

of alcohol and other drugs, head trauma, psychiatric disorder, aging,

304
and other disease factors affecting the central nervous system, as well

as more knowledge about preexposure cognitive functioning, and preexisting psychological dysfunction, with the deployment of appropriate reference, comparison, or control groups.

12. Prospective studies on neurotoxic and other toxicologic effects of solvents and other inhalants are needed. To date all studies are retrospective. Although these are difficult to visualize or design, it may be

possible to follow up controls of other studies who become inhalant

abusers.

13. More sophisticated neuroimaging studies, which combine metabolic

evaluations with imaging technology such as positron emission

tomography (PET), and single photon emission computed tomography (SPECT), should be employed to study both acute and chronic

effects of solvent inhalation.

14. Post-mortem analyses can identify links between solvents and disease

states or toxic effects on various tissues.

Psychosocial Studies

15. Studies on social marginality (viz., social problems such as poverty,

prejudice, and lack of opportunity) are essential next steps in research.

The focus on marginality may be exclusive of or inclusive of culture or

age groupings.

16. Studies on the psychological motivations for death (viz., retrospective

case histories) are needed among inhalant users. (For example, is

there a basis for hanging?) Special attention on apparent suicides may

reveal underlying inhalant use histories.

17. Exploratory studies on the motives for use of inhalants may utilize the

user’s perceived therapeutic effects of these inhalants (e.g., for their

anxiolytic and antidepressant effects). These results could establish

future research guidelines for the exploration of potential therapeutic

compounds.

305
18. Both cross-sectional and longitudinal studies are needed on such variables as school adjustment; family characteristics; deviance by age and

by peer group; violence and victims of abuse; and cultural identification factors, family risk factors, school risk factors, and psychosocial

consequences of inhalant use.

19. Laboratory analog studies are needed on such variables as social

responses of users; hostility and anger in both users and their families;

and learning and perception abilities of users.

20. Detailed and thorough ethnographic studies are needed on inhalant

dependent adults; such endeavors should encompass both intact and

broken families as well as homeless persons.

21. Studies have emphasized primary inhalant users. New studies are

needed on polydrug users who also use inhalants (secondary inhalant

users).

22. Studies are needed on specific occupations and occupational settings

and their influence on solvent abuse. For example, because of their

high level of exposure to “solvents,” tradespeople in the paint, cleaner,

and degreaser processing professions are important first groups to

study.

23. Select cultural studies are needed to focus on new solvent patterns in

vogue in special locales. For example, why are propane and butane

used by some adult populations, by some college students in the

United States, and by other groups in Great Britain, but their use is

unheard of in many other locales?

24. Studies are needed on the role of criminal activity and other deviant

behavior (including rebelliousness and influence of peer-sanctioned

deviance) in inhalant users.

25. Studies on school dropouts and the role of poor school adjustment are

needed. Studies examining the differences in learning styles between

inhalant users and others are potentially relevant for treatment and

prevention endeavors.

306
26. Studies are needed to examine the etiological relationship between

inhalant-using youths and learning disabilities.

27. The distinct age patterns displayed by solvent users need a more complete exploration. In particular, comparative studies across different

populations could be useful since age of onset may be interdependent

on varying patterns of social control.

28. More extensive studies on the role of the family and how it relates to

inhalant use among children are needed. The focus of such efforts

might include parenting styles, discipline, role modeling, family violence and abuse, and handling of family crises.

29. There is a need for more cross-national and cross-cultural studies.

30. Ethnographic studies on the user’s values, beliefs, routines, and consequences of their solvent using behaviors are needed. These should

include knowledge of the user’s perceptions of solvents and their

effects, and phenomenologic studies such as the settings, purposes,

motivations and functions of use for the user. These naturalistic

observation studies are an important prelude to epidemiological and

experimental studies.

31. Studies are needed on the types of solvents used and the motives for

use. Data from these studies may be helpful in determining the more

popular and/or dangerous substances.

Treatment and Prevention Research

Treatment and prevention approaches should be individually tailored to the

diverse inhalant-abusing target populations and should be critically evaluated

for the efficacy/outcome of these programs. Also, the best prevention programs are those based on solid research of what has worked, not what “ought”

to work. Adaptation rather than adoption of extant prevention approaches is

needed.

32. Conduct studies on how drug using groups differ from nonusers in

their perceptions and responses to drug prevention messages by

307
examining differences by age and by ethnicity, based on the content,

style, intensity, and the source of the message.

33. Comparative studies are needed to examine the prevalence rates

under various legal conditions, given that different locales have

imposed diverse laws regarding the use or sale of volatile solvents.

34. Studies should be designed using controlled evaluations of prevention

efforts with adequate comparison or control groups especially

designed for inhalant abusing populations.

35. Studies are needed to see how community-based treatment settings,

such as Community Assistance Programs (CAPS) can be adapted and

deployed for assisting inhalant abusers with special attention to the

unique needs of the target community, or target population, primarily

focusing on youngsters in school in their formative years. Employee

Assistance Programs (EAPs) may also be utilized to help the young

(not just the adult) inhalant user/abuser.

36. Studies are essential to determine “threshold” limits for exposure concentrations that markedly affect ongoing behavior and/or induce selfindulgence in “sniffing” and impair performance in animals and

humans, particularly in the workplace.

37. Evaluate the use of brainstem evoked responses (e.g., BAER’s) as a

sensitive screening test to identify individuals with early evidence of

central nervous system injury who thus may need treatment

intervention.

38. Determine if the lack of proper use of protective devices (e.g., respirators) in occupational settings encourages or relates to workers’

abuse of commercial volatile substances.

39. Investigate conditions that lead to the cessation of heavy use of

inhalants as well as initiation of inhalant use.

40. Studies to explore alternative treatments for young adult users should

include training in vocational counseling and testing, job training and

placement, training in employment interviewing skills, developing

308
methods for good work adjustment habits, and learning to conform to

the work environment.

41. Develop treatment programs that would address changing social as

well as psychological factors for the inhalant user. (Neither standard

psychotherapeutic approaches nor traditional inpatient drug rehabilitation have been notably successful for inhalant abusers).

42. Studies are needed to enhance multifaceted delivery of comprehensive

treatments for inhalant users, as inhalant users have extensive dysfunctions in many life domains.

43. Studies need to adapt treatment approaches to changing levels of

functioning, as inhalant users often experience neurological and

motor dysfunction that interfere with treatment.

Epidemiology

44. Longitudinal surveillance to detect and monitor trends and patterns of

volatile solvent abuse—especially for detecting new fad drugs, the role

of age-dependent use curves, and gender differences—are essential.

45. There is a need to study the outbreaks (endemics), the mode of

spread, and the dynamics of episodic patterns of inhalant abuse.

46. Clinical epidemiological studies, especially those related to inhalant

exposure, are essential.

47. Regional and local area epidemiological studies are desirable.

Economic Studies

48. Studies need to be conducted on the economic factors associated with

different rates of volatile solvent abuse, including the relationships to

specific levels of poverty; of availability and cost of solvents; or of

stigmatization or, in economically depressed areas, sanction associated with solvent use.

309
49. Studies on the costs to industry of volatile solvent abuse (e.g., costs

due to accidents, insurance, rehabilitation, and lowered productivity)

would aid prevention and treatment.

50. Studies on the national costs of solvent abuse are desirable.

51. Cost benefit studies for treatment and prevention where analyses of

the costs of inhalant-attendant criminal behavior should be compared

with the costs of prevention, treatment, and criminal justice

involvement.

310
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GPO Stock #017-024-1314-5 $3.75 NTIS PB #89-151989/AS $23.00

75 PROGRESS IN OPIOID RESEARCH. PROCEEDINGS OF THE 1986

INTER- NATIONAL NARCOTICS RESEARCH CONFERENCE. John W.

Holaday, Ph.D.; Ping-Yee Law, Ph.D.; and Albert Herz, M.D., eds.

GPO out of stock NCADI out of stock

Not available from NTIS

76 PROBLEMS OF DRUG DEPENDENCE, 1986. PROCEEDINGS OF THE

48TH ANNUAL SCIENTIFIC MEETING, THE COMMITTEE ON PROBLEMS

OF DRUG DEPENDENCE, INC. Louis S. Harris, Ph.D., ed.

GPO out of stock NCADI out of stock

NTIS PB #88-20811l/AS $53.00

77 ADOLESCENT DRUG ABUSE: ANALYSES OF TREATMENT

RESEARCH. Elizabeth R. Rahdert, Ph.D., and John Grabowski, Ph.D., eds.

GPO Stock #017-024-01348-0 $4.00 NCADI out of stock

NTIS PB #89-125488/AS $23.00

78 THE ROLE OF NEUROPLASTICITY IN THE RESPONSE TO DRUGS.

David P. Friedman, Ph.D., and Doris H. Clouet, Ph.D., eds.

GPO out of stock NTIS PB #88-245683/AS $31.00

79 STRUCTURE-ACTIVITY RELATIONSHIPS OF THE CANNABINOIDS.

Rao S. Rapaka, Ph.D., and Alexandros Makriyannis, Ph.D., eds.

GPO out of stock NTIS PB #89-109201/AS $31.00

312
80 NEEDLE SHARING AMONG INTRAVENOUS DRUG ABUSERS:

NATIONAL AND INTERNATIONAL PERSPECTIVES. Robert J. Battjes,

D.S.W., and Roy W. Pickens, Ph.D., eds.

GPO out of stock NTIS PB #88-236138/AS $31.00

81 PROBLEMS OF DRUG DEPENDENCE, 1987. PROCEEDINGS OF THE

49TH ANNUAL SCIENTIFIC MEETING, THE COMMITEE ON PROBLEMS

OF DRUG DEPENDENCE, INC. Louis S. Harris, Ph.D., ed.

GPO Stock #017-024-01354-4 $17.00 NTIS PB #89-109227/AS Contact

NTIS for price

82 OPIOIDS IN THE HIPPOCAMPUS. Jacqueline F. McGinty , Ph.D., and

David P. Friedman, Ph.D. eds.

GPO out of stock NTIS PB #88-245691/AS $23.00

83 HEALTH HAZARDS OF NITRITE INHALANTS. Harry W. Haverkos,

M.D., and John A. Dougherty, Ph.D., eds.

GPO out of stock NTIS PB #89-125496/AS $23.00

84 LEARNING FACTORS IN SUBSTANCE ABUSE. Barbara A. Ray, Ph.D.,

ed.

GPO Stock #017-024-01353-6 $6.00 NTIS PB #89-125504/AS $31.00

85 EPIDEMIOLOGY OF INHALANT ABUSE: AN UPDATE. Raquel A.

Crider, Ph.D., and Beatrice A. Rouse, Ph.D., eds.

GPO Stock #017-024-01360-9 $5.50 NTIS PB #89-123178/AS $31.00

86 COMPULSORY TREATMENT OF DRUG ABUSE: RESEARCH AND

CLINICAL PRACTICE. Carl G. Leukefeld, D.S.W., and Frank M. Tims,

Ph.D., eds.

GPO Stock #017-024-01352-8 $7.50 NTIS PB #89-151997/AS $31.00

87 OPIOID PEPTIDES: AN UPDATE. Rao S. Rapaka, Ph.D. and Bhola N.

Dhawan, M.D., eds.

GPO Stock #017-024-01366-8 $7.00 NTIS PB #89-158430/AS $45.00

88 MECHANISMS OF COCAINE ABUSE AND TOXICITY. Doris H. Clouet,

Ph.D., Khursheed Asghar, Ph.D., and Roger M. Brown, Ph.D., eds.

GPO Stock #017-024-01359-5 $11.00 NTIS PB #89-125512/AS $39.00

313
89 BIOLOGICAL VULNERABILITY TO DRUG ABUSE. Roy W. Pickens,

Ph.D., and Dace S. Svikis, B.A., eds.

GPO Stock #017-022-01054-4 $5.00 NTIS PB #89-125520/AS $23.00

90 PROBLEMS OF DRUG DEPENDENCE, 1988. PROCEEDINGS OF THE

50TH ANNUAL SCIENTIFIC MEETING. THE COMMITTEE ON PROBLEMS

OF DRUG DEPENDENCE, INC., Louis S. Harris, Ph.D., ed.

GPO Stock #017-024-01362-5 $17.00

91 DRUGS IN THE WORKPLACE: RESEARCH AND EVALUATION DATA.

Steven W. Gust, Ph.D.; and J. Michael Walsh, Ph.D., eds.

GPO Stock #017-024-01384-6 $10.00 NTIS PB #90-147257/AS $39.00

92 TESTING FOR ABUSE LIABILITY OF DRUGS IN HUMANS. Marian W.

Fischman, Ph.D.; and Nancy K. Mello, Ph.D., eds.

GPO Stock #017-024-01379-0 $12.00 NTIS PB #90-148933/AS $45.00

93 AIDS AND INTRAVENOUS DRUG USE: FUTURE DIRECTIONS FOR

COMMUNITY-BASED PREVENTION RESEARCH. C.G. Leukefeld, D.S.W.;

R.J. Battjes, D.S.W.; and Z. Amsel, Ph.D., eds.

GPO Stock #017-024-01388-9 $10.00 NTIS PB #90-148941/AS $39.00

94 PHARMACOLOGY AND TOXICOLOGY OF AMPHETAMINE AND

RELATED DESIGNER DRUGS. Khursheed Asghar, Ph.D.; Errol De Souza,

Ph.D., eds.

GPO Stock #017-024-01386-2 $11.00 NTIS PB #90-148958/AS $39.00

95 PROBLEMS OF DRUG DEPENDENCE, 1989. PROCEEDINGS OF THE

51st ANNUAL SCIENTIFIC MEETING. THE COMMITTEE ON PROBLEMS

OF DRUG DEPENDENCE, INC., Louis S. Harris, Ph.D., ed.

GPO Stock #017-024-01399-4 $21.00 NTIS PB #90-237660/AS $67.00

96 DRUGS OF ABUSE: CHEMISTRY, PHARMACOLOGY, IMMUNOLOGY,

AND AIDS. Phuong Thi Kim Pham, Ph.D. and Kenner Rice, Ph.D., eds.

GPO Stock #017-024-01403-6 $8 NTIS PB #90-237678/AS $31.00

97 NEUROBIOLOGY OF DRUG ABUSE: LEARNING AND MEMORY.

Lynda Erinoff, ed.

GPO Stock #017-024-01404-4 $8 NTIS PB #90-237686/AS $31.00

314
98 THE COLLECTION AND INTERPRETATION OF DATA FROM HIDDEN

POPULATIONS. Elizabeth Y. Lambert, M.S., ed.

GPO Stock #017-024-01407-9 $4.75 NTIS PB #90-237694/AS $23.00

99 RESEARCH FINDINGS ON SMOKING OF ABUSED SUBSTANCES. C.

Nora Chiang, Ph.D. and Richard L. Hawks, Ph.D., eds.

GPO Stock #017-024-01412-5 $5.00 NTIS PB #91-141119 $23.00

100 DRUGS IN THE WORKPLACE: RESEARCH AND EVALUATION

DATA. VOL II. Steven W. Gust, Ph.D.; and J. Michael Walsh, Ph.D., eds.

GPO Stock #017-024-01458-3 $8.00

101 RESIDUAL EFFECTS OF ABUSED DRUGS ON BEHAVIOR. John W.

Spencer, Ph.D. and John J. Boren, Ph.D., eds.

GPO Stock #017-024-01426-7 $6.00 NTIS PB #91-172858/AS $31.00

102 ANABOLIC STEROID ABUSE. Geraline C. Lin, Ph.D. and Lynda Erinoff,

Ph.D., eds.

GPO Stock #017-024-01425-7 $8.00 NTIS PB #91-172866/AS $31.00

103 DRUGS AND VIOLENCE; CAUSES, CORRELATES, AND

CONSEQUENCES. Mario De La Rosa, Ph.D., Elizabeth Y. Lambert, M.S., and

Bernard Gropper, Ph.D., eds.

GPO Stock #017-024-01427-3 $9.00 NTIS PB #91-172841/AS $31.00

104 PSYCHOTHERAPY AND COUNSELING IN THE TREATMENT OF

DRUG ABUSE. Lisa Simon Onken, Ph.D. and Jack D. Blaine, M.D., eds.

GPO Stock #017-024-01429-0 $4.00 NTIS PB #91-172874/AS $23.00

105 PROBLEMS OF DRUG DEPENDENCE, 1990. PROCEEDINGS OF THE

52nd ANNUAL SCIENTIFIC MEETING. THE COMMITEE ON PROBLEMS

OF DRUG DEPENDENCE, INC., Louis S. Harris, Ph.D., ed.

GPO Stock #017-024-01435-4 $22.00

106 IMPROVING DRUG ABUSE TREATMENT. Roy W. Pickens, Ph.D.; Carl

G. Leukefeld, D.S.W.; and Charles R. Schuster, Ph.D., eds.

GPO Stock #017-024-01439-7 $12.00

NTIS PB #92-105873 Paperback $50.00 Microfiche $19.00

315
107 DRUG ABUSE PREVENTION INTERVENTION RESEARCH:

METHODOLOGICAL ISSUES. Carl G. Leukefeld, D.S.W., and William J.

Bukoski, Ph.D., eds.

GPO Stock #017-024-01446-0 $9.00

NTIS PB #92-160985 Paperback $35.00 Microfiche $17.00

108 CARDIOVASCULAR TOXICITY OF COCAINE: UNDERLYING

MECHANISMS. Pushpa V. Thadani, Ph.D., ed.

GPO Stock #017-024-01446-0 $7.00

NTIS PB #92-106608 Paperback $35.00 Microfiche $17.00

109 LONGITUDINAL STUDIES OF HIV INFECTION IN INTRAVENOUS

DRUG USERS: METHODOLOGICAL ISSUES IN NATURAL HISTORY

RESEARCH. Peter Hartsock, Dr.P.H., and Sander G. Genser, M.D., M.P.H.,

eds.

GPO Stock #017-024-01445-1 $4.50

NTIS PB #92-106616 Paperback $26.00 Microfiche $12.50

110 THE EPIDEMIOLOGY OF COCAINE USE AND ABUSE. Susan Schober,

Ph.D., and Charles Schade, M.D., M.P.H., eds.

GPO Stock #017-024-01456-7 $11.00

NTIS PB #92-14624-0 Paperback $43.00 Microfiche $17.00

111 MOLECULAR APPROACHES TO DRUG ABUSE RESEARCH: VOLUME

I. Theresa N.H. Lee, Ph.D., ed.

NTIS PB #92-135743 Paperback $35.00 Microfiche $17.00

112 EMERGING TECHNOLOGIES AND NEW DIRECTIONS IN DRUG

ABUSE RESEARCH. Rao S. Rapaka, Ph.D.; Alexandros Makriyannis, Ph.D.;

and Michael J. Kuhar, Ph.D., eds.

GPO Stock #017-024-01455-9 $11.00

113 ECONOMIC COSTS, COST EFFECTIVENESS, FINANCING, AND

COMMUNITY-BASED DRUG TREATMENT. William S. Cartwright, Ph.D.,

and James M. Kaple, Ph.D., eds.

NTIS PB #92-155795 Paperback $35.00 Microfiche $17.00

114 METHODOLOGICAL ISSUES IN CONTROLLED STUDIES ON

EFFECTS OF PRENATAL EXPOSURE TO DRUG ABUSE. M. Marlyne

Kilbey, ph.D., and Khursheed Asghar, Ph.D., eds.

GPO Stock #017-024-01459-1 $12.00

316
NTIS PB #92-146216 Paperback $43.00 Microfiche $17.00

115 METHAMPHETAMINE ABUSE: EPIDEMIOLOGIC ISSUES AND

IMPLICATIONS. Marissa A. Miller, D.V.M., M.P.H., and Nicholas J. Kozel,

M.S., eds.

GPO Stock #017-024-01460-5 $4.00

116 DRUG DISCRIMINATION: APPLICATIONS TO DRUG ABUSE

RESEARCH. R.A. Glennon, Ph.D., T.U.C. Jarbe, Ph.D., and J. Frankenheim,

Ph.D., eds.

GPO Stock #017-024-01470-2 $13.00

117 METHODOLOGICAL ISSUES IN EPIDEMIOLOGY, PREVENTION,

AND TREATMENT RESEARCH ON DRUG-EXPOSED WOMEN AND

THEIR CHILDREN. M. M. Kilbey, Ph.D. and K. Asghar, Ph.D., eds.

GPO Stock #017-024-01472-9 $12.00

118 DRUG ABUSE TREATMENT IN PRISONS AND JAILS. C.G. Leukefeld,

D.S.W. and F. M. Tims, Ph.D., eds.

GPO Stock #017-024-01473-7 $16.00

119 PROBLEMS OF DRUG DEPENDENCE 1991: 53rd ANNUAL

SCIENTIFIC MEETING. The Committee on Problems of Drug Dependence,

Inc. Louis Harris, Ph.D., ed.

GPO Stock #017-024-01474-5 $22.00

120 BIOAVAILABILITY OF DRUGS TO THE BRAIN AND THE BLOODBRAIN BARRIER. Jerry Frankenheim, Ph.D., and Roger M. Brown, Ph.D.,

eds.

GPO Stock #017-024-01481-8 $10.00

121 BUPRENORPHINE: AN ALTERNATIVE TREATMENT FOR OPIOID

DEPENDENCE. Jack D. Blaine, Ph.D. ed.

GPO Stock #017-024-01482-6 $5.00

122 RESEARCH METHODS IN WORKPLACE SETTINGS. Steven W. Gust,

Ph.D., Helan Axel, M.A., and Dennis J. Crouch, M.B.A., eds.

123 ACUTE COCAINE INTOXICATION: CURRENT METHODS OF

TREATMENT. Heinz Sorer, Ph.D., ed.

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124 NEUROBIOLOGICAL APPROACHES TO BRAIN-BEHAVIOR

INTERACTION. Roger M. Brown, Ph.D., and Joseph Fracella, Ph.D., eds.

125 ACTIVATION OF IMMEDIATE EARLY GENES OF ABUSE. Reinhard

Grzanna, Ph.D., and Roger M. Brown, Ph.D., eds.

126 MOLECULAR APPROACHES TO DRUG ABUSE RESEARCH VOLUME

II: STRUCTURE, FUNCTION, AND EXPRESSION. Theresa N.H. Lee,

Ph.D., eds.

127 PROGRESS AND ISSUES IN CASE MANAGEMENT. Rebecca Sager

Ashery, D.S.W., ed.

128 STATISTICAL ISSUES IN CLINICAL TRIALS FOR TREATMENT OF

OPIATE DEPENDENCE. Ram B. Jain, Ph.D., ed.

318
National Institute on Drug Abuse

NIH Publication No. 93-3480

Printed 1992