)
FEDERAL SECURITY AGENCY, Oscar R. Ewing, Administrator
Public Health Service, Leonard A. Scheele, Surgeon General
National Institutes of Health, R. E. Dyer, Director
National Cancer Institute, John R. Heller, Director
Cancer Control Branch, Austin V. Deibert, Chief
For sale by the Superintendent of Documents, U. S. Government Printing Office, Washington 25, D. C.
Price 20 cents
ENVIRONMENTAL CANCER
W. C. HUEPER, M. D., Environmental Cancer Section
• * *
CANCER CONTROL BRANCH, NATIONAL CANCER INSTITUTE
INTRODUCTION
DEC i052
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As long as man has existed, his surroundings have been at once his chief
support and his chief enemy. The human being is not an independent organ¬
ism, imposed upon an existing environment. He is, rather, an inseparable
part of it. He grew with it and out of it; he always depends on it; and he
never can escape it. But to some extent he can control his environment.
Where it is harmful, he should do so.
In relatively modern times, the industrial activities of man have added
a number of entirely new artificial factors to his natural environment. Many
of them contribute to the comfort and the pleasures of life. Yet in the process
of their manufacture and use a whole new spectrum of environmental "poi¬
sons" has been added to the hazards with which mankind has to contend.
Some of these poisons act obviously and swiftly, and can be controlled
because of their very violence. Others pursue a slow, nearly imperceptible
course, and exhibit their virulence in end-results which often seem to bear
no relation to their origins. Of these, many cause a gradual wastage of the
individual organism by means of direct poisoning; others result in chaotic
cell growths, arising after a lengthy latent period, and causing a sudden and
sometimes inexplicable illness which, unless discovered at an early stage,
usually results in death. It is with these latter effects of an industrial
civilization that we are concerned—the effects known as environmental cancers.
The destructive growth of undifferentiated body cells which is known as
cancer has been a recognized medical problem since eight hundred years
before the birth of Christ. In the library of Nineveh there was an inscrip¬
tion, dating from about that time, which described a carcinoma of the breast.
But it was not until the sudden, explosive growth of Western technology,
2
toward the end of the last century, that medical science obtained the tools
necessary for a concentrated attack upon human disease. Because of their
more dramatically obvious lethal nature, endemic parasitical ailments came
under medical scrutiny before most other types of illness; and these con¬
tagious diseases have for the most part fallen before the organized technical
onslaught of modern medicine.
But now we are on the threshold of one of the greatest of all battles of
man against his environment: the battle against cancer. Today, less than
one percent of all cancers have a known or even a suspected cause. Yet this
etiologic fraction of one percent is the first wedge of knowledge into a hereto¬
fore impenetrable mystery, achieved after an enormous expenditure of time,
research, intelligence, and money. That specialists in cancer have been able
to identify even this small part of the causes of cancer is as great a step for¬
ward, in some ways, as was the discovery of the first pathogenic micro¬
organisms that led to the subsequent conquest of many of the most dangerous
infectious diseases.
With few exceptions, the causes of cancer thus far discovered have been
found to be of external origin. While this by no means permits the conclusion
that all cancers are of exogenous causation, it does indicate that further
research may well uncover many more external—and therefore controllable—
cancerigenic agents.
But the knowledge of a cause in medicine, and control of such a cause,
are two completely different elements of this science. The first rarely if
ever leads automatically to the second; and the second involves a much wider
variety of human activity. It includes, in addition to the purely medical
aspects, the planning, coordination and carrying out of a Nation-wide program
of remedial legislation, medical education, labor and management super¬
vision, public health controls, and citizen indoctrination.
It is the purpose of this pamphlet to present in brief form the known and
suspected environmental causes of cancer, the sources from which they arise,
the methods whereby they are discovered, and their carcinogenic dangers are
demonstrated, and the programs of control which are essential if these causes
of cancer are to be eliminated or at least greatly reduced in potency.
3
CAUSATIVE FACTORS
diet
habits
The human being may be exposed to one or more of the known or suspected
>••••••• external cancer-producing agents in a variety of ways. Medicinal prepara¬
tions and devices, dietary deficiences, certain habits, and a few of the environ¬
mental factors, all offer some cancerigenic hazards; but the greatest number
of known carcinogens are found in connection with man's occupational
activities.
medicine In the medical field, preparations containing arsenicals and coal tar have
been known to cause cancer of the skin. Medicinal exposure to X-rays and
radium, in the treatment of often nonmalignant diseases, has resulted in
cancers of the irradiated tissues in some patients.
Dietary deficiencies, particularly of proteins and vitamin B factors, are
thought to be responsible for the excessive incidence of cancer of the liver
among African Negroes and the inhabitants of Java. Thyroid cancers seem
to be related to the occurrence of endemic goiter in population groups suffer¬
ing from a dietary iodine deficiency.
Although there is no definite evidence that tobacco is carcinogenic when
smoked or chewed, there is an abnormal incidence of cancer of the mouth in
India and the Philippines, where the people chew tobacco-betel nut quids,
or place tobacco-lime quids in the groove behind the lower lip. Mouth
cancers are also unusually frequent in a certain tribe in India which smokes
cigars with the lighted end in the mouth, and thus contracts frequent burns,
as well as a concentrated dosage of tobacco tars,
environment, natural The natural environment contains only a few recognized carcinogens. Of
these, solar radiation is one of the best proved, particularly as it affects light-
skinned people who become overexposed for long periods of time to the carci¬
nogenic ultraviolet radiation in southern dry and sunny climates. An abnor¬
mally high arsenic content in drinking water has been shown to cause cancer
of the skin and of the internal organs. Infections with the parasite Schisto¬
soma hematobium, common among the fellahs of Egypt, are apparently related
to the high incidence of cancer of the bladder found there.
environment, artificial In the artificial environment which has been created by our industrial civiliza¬
tion, soot and certain waste products from the fractionation and distillation
4
chemical (inorganic)
physical agents
gamma rays
polycj^^^rbons
chemical (organic)
parasitic
schist
tobium
clonifdir^iiisis*
,
viruses
estrogens*
'"conflicting evidence
of coal and petroleum, including shale oil, have carcinogenic potentialities.
Likewise the wastes resulting from the smelting and processing of certain
metals may give carcinogenic properties to the air, water, and soil within
the "fume zone" of plants producing them. All types of radioactive emana¬
tions are similarly dangerous in the general environment.
occupations But it is in the occupational activities of an industrial society that most of the
carcinogenic dangers are found. Here workers come into close and prolonged
contact with substances which either have never before existed in the natural
environment, or have existed in such weak concentrations as to be relatively
harmless. A chart of the major known occupational carcinogens, some of
which are also active in other connections, appears herewith.
MECHANISM OF ACTION
direct primary
indirect primary
The known or suspected extrinsic carcinogens act on the human organism in
one of three different ways. Some carcinogens directly cause cancer, among
them the aromatic amines, tar, mineral oils, and their derivatives.
Other agents coming in contact with certain human tissues seem to elicit
cancers by producing endogenous carcinogenic substances within the exposed
tissues. These comprise all the physical rays and radiations, and certain
metals or metallic compounds, including arsenicals, chromates, nickel
carbonyl, and possibly asbestos.
indirect secondary A third group acts even more indirectly. The azo dyes and the suspected
chlorinated aliphated hydrocarbons, along with a few dietary imbalances,
are thought to cause metabolic disturbances in certain organs, such as the
liver, which in turn result in the formation of endogenous carcinogens.
routes of exposure All of these carcinogens may act through one or more of the following routes
of exposure: skin contact, respiratory contact, ingestion, and parenteral intro¬
duction. For example, radioactives may cause skin cancer when the skin is
overly exposed to them; lung cancer when radioactive emanations and dusts
are inhaled; and leukemic manifestations, which are a sort of cancer, when
the system is subjected to a very slight but prolonged contact with electronic
energy. Bone cancers may also be caused by the ingestion of radioactive
substances, or by medicinal overexposure to X-rays.
6
CHARACTERISTICS
statistical
There are a number of statistical and clinical characteristics of environmental
cancers which are helpful in their discovery and evaluation. Some apply to
the cancers themselves; some to the carcinogens. While not always signifi¬
cant when considered singly, these characteristics when fitted together tend to
form a pattern that is typical for environmental carcinogenesis.
Moreover, it is not necessary that all of these characteristics be found
in a given group or a given environment before an environmental origin can
be suspected. It usually is essential, however, that one or the other of the
elements mentioned below under Point One be presented before an environ¬
mental etiology can be prognosticated.
The major statistical characteristics of environmental cancers follow:
1. An excessive incidence of a certain type of cancer among members of a
given occupational group suggests the existence of an environmental carci¬
nogen. Likewise, the presence of an industry using known or suspected
carcinogens indicates that occupational cancers may be found in the working
population.
2. The rate of incidence among exposed individuals, and the length of the
average latent period found, depend on the potency of the carcinogen and
on the duration and intensity of exposure to it.
3. Where a racially mixed population exists, these relations are modified in
regard to solar cancers and to cancers caused by mineral oils and tar products,
since dark-skinned peoples are less susceptible to such carcinogens than are
the light-skinned groups.
4. Age at onset of exposure and average length of latent period determine
within reasonable bounds the manifestation age of occupational cancer.
Neither heredity nor advanced age seem to have any appreciable influence
on susceptibility to or incidence of this type of malignant tumor.
5. Occupational cancers occur predominantly in males, since more males
come in contact with industrial carcinogens than do females. The existing
differences in sex distribution of cancer are in general a reflection of this fact,
and do not indicate that there is any special susceptibility to occupational
cancer on the part of the male sex.
8
clinical There are three major clinical factors which characterize environmental
cancers:
1. The site of exogenously caused cancers in the body depends on the phys¬
ical and chemical properties of the carcinogen, and on the type, intensity, and
duration of exposure to it. Many such cancers develop at the point where
the carcinogen exerts the most intense and prolonged action, regardless of
the original route of primary contact with it. With skin cancers the contact
route and the site are usually identical, but with internal cancers they often
differ.
2. A high rate of primary multiplicity, or of two or more simultaneous cancers
not caused by metastasis, is characteristic of occupational cancer, and is the
result of the action of a potent carcinogen and of an intense and long-continued
exposure to it.
3. Characteristic occupational lesions, such as arsenic and tar dermatoses,
actinic dermatitis, and radiation osteitis, are precancerous warnings of occupa¬
tional cancers to come.
CANCER AND INDUSTRY
radioactive substances
The most significant part of the environmental cancer problem is its occupa¬
tional aspect. Fully 90 percent of the known environmental carcinogens
never existed in dangerous concentrations until industrial processes brought
workers into constant and close contact with them.
The growth of recognized exogenous cancers parallels in startling fashion the
growth of those industries and professions in which extrinsic carcinogens are
a factor. One of the most obvious is the mining, manufacture, and use of
radioactive materials, and the use of X-ray apparatus. It is estimated that
50 percent of the uranium miners at Joachimsthal, in Czechoslovakia, and up
to 80 percent of the cobalt miners in the radioactive mines at Schneeberg, die
of lung cancer, most probably as a result of radioactive poisons. From the
first recorded appearance of a recognized X-ray cancer in 1902, the spread
of radiation cancers has automatically followed new developments and new
uses of these dangerous materials and instruments. A case in point is the
9
environmental carcinogens NAME
SOOT
ARSENIC
PARAFFIN OIL
SHALE OIL
PITCH & TAR
CRUDE OILS (SOME)
SUN (ULTRAVIOLET)
AROMATIC AMINES
ROENTGEN RAYS
SCHISTOSOMA HEMATOBIUM
ROENTGEN RAYS, RADIUM
ANTHRACENE OIL
BETEL NUT, TOBACCO
DIET DEFICIENCY
RADIUM
LUBRICATING OILS
CREOSOTE
BENZOL
URANIUM
RADIOACTIVE RAYS
CHROMATES
NICKEL CARBONYL
ASBESTOS
RADIOACTIVE RAYS
TAR FUMES
DATE
1775
1822
1875
1876
DISCOVERER
Pott
Ayrton
Volkmann
Bell
1876
1879
1893
1895
1902
1911
1911
1913
1915
1919
1920
1922
1924
1928
1929
1931
1932
1932
1934
1934
1936
Manouvriez
Harting & Hesse
Unna
Rehn
Frieben
Ferguson
Von jagicz, Schwartz A Von
Siebenrock
Rambousek
Davis
Mouchet & Gerard
Leitch & Sequira
Southam & Wilson
Cookson
Delore & Bergamo
Lowy
Martland
Alwens
Stephens
Wood & Gloyne
Neitzel
Kahawata
ORGANS AFFECTED
Skin (scrotum)
Skjn
Skin
Skin
Skin
Skin
Skin
Bladder
Skin
Bladder
Bone marrow (leu-
Itfiniq)
Skin
Mouth
Liver
Skin
Skin
Skin
Bone marrow (leu-
kemia)
Lung
Bone
Lung
Nasal sinuses, lung
Lung
Lung
Lung
NATURE OF EXPOSURE*
Occ. (chimney sweeps)
Occ., env.
Occ. (lignite & shale oil indust)
Occ.
Occ.
Occ.
Occ. (farmers, sailors)
Occ. (dye industry)
Occ., med.
Env., occ. (Egypt)
Occ., med.
Occ.
Habit (India, Malay)
Env. (poverty diets, Africans, Chinese)
Occ. and med.
Occ. (mule spinners)
Occ.
Occ.
Occ.
Occ. & med.
Occ.
Occ.
Occ.
Occ. & med.
Occ.
*occ—occupational
env—environmental
med—medicinal
tragedy of the luminous dial painters in the United States, many of whom
have, since 1928, died of bone cancers resulting from their habit of wetting
the radioactive paint brushes with their lips,
dyes Similarly, bladder cancers resulting from appreciable exposure to certain
dye intermediates have closely followed the establishment of industries
making or using these chemicals. In almost every case the elapsed time
between the first possible exposure and the recognized appearance of the
cancers has borne a direct relation to the known average latent period for
the development of such lesions.
The following timetable of first reports of occupational cancers shows
how closely they are related to the original establishment of the industries
producing or using the carcinogens involved.
FUTURE OCCUPATIONAL CANCER HAZARDS
It is obvious that the environmental cancer spectrum is only partially known.
New carcinogens are discovered from time to time, and undoubtedly will
continue to be.
The most dangerous areas in our modern environment, from the point of
view of future cancer hazards, are the following:
radioactive substances
1. The field of radioactive substances—uses, scien¬
tific, medical, industrial, and military—wherever
radiations obtained from radioactive materials, from
X-rays, or from other sources, come in contact with
the human being.
11
. chemicals
2. The whole area of hydrocarbon and metallurgic
research and development. This includes the high-
temperature distillation and fractionation of petro¬
leum, the production and processing of shale oil,
bitumen, and coal by recently developed methods of
cracking and hydrogenation, and the manufacture
of new organic chemicals from these substances.
synthetic chemicals
3. More generally, the wide field of organic chem¬
istry, which is developing thousands of new synthetic
chemicals often without adequate testing for cancer-
producing properties. These, as well as the other
chemicals, are entering our environment through
an enormous number of routes, many of which
may subject workers or users to dangerous concen¬
trations of now-unknown carcinogens. Such ma¬
terials are becoming increasingly common in in¬
dustry; in agriculture as insecticides and synthetic
fertilizers; and in medicines, prepared foods, and
cosmetics, all designed for direct personal use and
consequently all presenting possible carcinogenic
hazards.
EPIDEMIOLOGY The two basic techniques of medical research, epidemiology and experimenta-
• ••••••••••••••••••••••••••• tion, provide most of the important knowledge on the existence and incidence
of environmental cancer. Epidemiological studies of such cancers are among
the most complex and difficult of all statistical operations, because of the great
number of special factors which enter each project.
12
The epidemiology of environmental cancer falls into two major divisions:
general population studies on regional, racial, sex and other very broad bases;
and special population studies, either community, industrial plant, or tribal,
usually in relation to some suspected carcinogen,
solar cancer Significant results on the relation of solar cancers to intensity and duration
of sunlight have been obtained from the first, generalized type of study. The
chart of skin cancer incidence in certain United States cities shows important
variations in proportion to differences in total annual solar radiation. Gen¬
eralized studies of this type are usually based on already existing disease
incidence figures, such as those published by the Public Health Service of the
Federal Security Agency.
RELATION OF INTENSITY OF SUNLIGHT
TO SKIN CANCERS
skin cancer rates and average annual sunlight
as percentage of total possible sunlight.
skin cancers per 100,000 popu¬
lation
city
percent of total possible sun¬
light
140
DALLAS
60%-80%
129
NEW ORLEANS
62%-64%
37
PITTSBURGH
50%-57%
24
DETROIT
40%-25%
13
aromatic amine cancer The more specialized type of epidemiological analysis results in comparative
incidence statistics such as those shown in the chart on cancer of the bladder
caused by certain aromatic amines. In this type of study the data are usually
collected by the investigator directly from hospital, public health agency,
industrial, and other local sources.
14
EXPERIMENTATION
The bladder cancer chart pictures the result of an epidemiological study
in a single plant. It differentiates very strongly between those workers most
exposed to the carcinogen and those less exposed, and also gives figures on
bladder cancer incidence in the county in which the plant exists, and in the
state as a whole.
Most of the important data on environmental cancers have been discov¬
ered through the careful, scientific use of one or the other of these two types
of statistical analysis.
Although epidemiological studies of environmental cancers are strongly indic¬
ative of the cancer-producing properties of the rays or substances involved,
they are not always conclusive. Other factors may be at work in the sample
populations studied, though it is not likely that such factors would cause the
abnormal incidence figures which often result from careful statistical
analyses.
However, conclusive evidence of the cancer-producing qualities of
suspected agents is obtained when cancers are elicited in experimental animals
after exposure to the carcinogen. This proof of carcinogenicity has been
developed for a large number of agents, the great majority of which are
products of our industrial environment.
The fact that there are a few animals in which experimental cancers
produced by certain specific carcinogens cannot be elicited is very significant.
It shows that environmental carcinogens can be as "species-specific," or as
selective in their effect upon experimental animals, as are many of the micro¬
organisms which are responsible for the spread of contagious diseases. This
selectivity is probably due to differences in metabolization in various animals,
or in their reactivity to the specific carcinogen involved.
The species specificity factor makes it obvious that no suspected carci¬
nogen can ever be absolved of dangerous possibilities merely as a result of
testing on one animal variety. It may happen that that species is refractory
to the particular carcinogen. Several species must be used before an agent's
carcinogenic properties can be clearly evaluated. The special anatomical
15
peculiarities of each species must also be taken into consideration, to assure
that proper contact with the carcinogen will be achieved for every type of
animal used.
reproduction of
occupational cancers in
experimental animals
AGENT
ORGAN
SPECIES
SUCCESSFUL
UNSUCCESSFUL
SOOT
Skin
Rabbit,* Mouse
Lung
Mouse
ARSENICALS
Skin
Mouse,* Hairless Rat*
Rabbit, Rat
PARAFFIN OIL
Skin
Mouse
SHALE OIL
Skin
Mouse
Lung
Mouse
PITCH AND TAR
Skin
Mouse, Rat, Rabbit, Dog
Monkey
CRUDE OILS
Skin
Mouse
ULTRAVIOLET RAYS (SUN)
Skin
Rat, Mouse
Rabbit
ROENTGEN RAYS
Skin
Rabbit, Mouse, Rat
Bone
Rabbit
Bone Marrow
Mouse
ANTHRACENE OIL
Skin
Mouse
DIET DEFICIENCY
Liver
Rat
RADIOACTIVE SUBSTANCES
Skin
Mouse, Rabbit
Bone
Rabbit, Guinea Pig
Lung
Mouse
Bone Marrow
LUBRICATING OILS (SOME)
Skin
Mouse
CREOSOTE
Skin
Mouse
BENZOL
Bone Marrow
Mouse*
CHROMATES
Lung
NICKEL CARBONYL
Lung
ASBESTOS
Lung
Mouse*
Guinea Pig
TAR FUMES
Lung
Mouse*
BETA-NAPHTHYL AMINE
Bladder
Dog
Rabbit,* Rat, Mouse
BENZIDINE
♦controversial evidence
Dog
'
CONTROL PROGRAM
Nearly all of the known cancer-causing agents previously listed are widely
used in America's industrial processes. Indeed, there is hardly a single
industry in which at some point one or more carcinogens are not found, and
are potentially dangerous to the people handling them unless proper
precautions are taken.
This continued exposure to the environmental cancer danger of workers,
technicians, scientists, management personnel, and even the populations of
communities near the plants, constitutes an urgent public problem. Impor¬
tant industries using carcinogenic agents are expanding, such as radiation
dye plants, processors of the various forms of hydrocarbon, metals,
users,
solvents, etc.; and new processes involving similar or new types of exposure
are constantly being developed. A program of social and technical controls
over these hazards must be worked out and put into effect at the earliest
possible moment.
An adequate program of control against environmental cancer in Amer¬
ican factories and in any American community which is exposed to extrinsic
carcinogens should include the following essential points,
technical 1. Known carcinogenic agents should either be eliminated from industrial,
civilian or military use whenever practical and possible, or the degree of
prolonged occupational or environmental exposure to them should be
depressed to a safe level.
2. Safety procedures should be introduced in all plants where carcinogenic
agents are handled. They should include not only protection of the individ¬
ual workers by enclosing the manufacturing processes, but also protection of
the whole plant and of the community at large by preventing the escape of
carcinogenic wastes into the atmosphere, the water, or the soil. All new
plants should be built with these controls constantly uppermost in the minds
of the designers and builders.
3. Adequate protective clothing, respirators, and gloves should be given
workers handling carcinogenic substances; separate lockers should be pro¬
vided for work and street clothes; shower facilities should be installed for all
workers; and a thorough indoctrination of exposed workers in the methods
17
of avoiding exposure to the carcinogens they handle should be made a part
of all personnel routines.
4. Periodic and extensive medical supervision of all exposed workers should
become standard. These examinations should continue at stated intervals
even after the individual worker is no longer in contact with the carcinogen,
whether he is still employed in the same plant or not.
social 1. All plants and laboratories manufacturing, handling or using carcinogenic
substances should be licensed by the States or the Federal Government, and
regular inspections should be made to supervise plant control methods, tech¬
nical, sanitary and medical. Regulations should cover definitions of safe
shipping techniques and of proper warning labels for shipping containers.
2. State compensation laws should be amended to cover all aspects of occupa¬
tional carcinogenesis, for the protection both of workers and of management.
3. All precancerous and cancerous lesions should be added to the list of
legally notifiable diseases. Preferably these notifications should be central¬
ized in the hands of State or Federal agencies.
4. Effective cooperation between industry and government should be estab¬
lished through an educational campaign and through conferences. Without
this, little or none of the rest of the control program can be successfully
initiated or carried out.
18
CONCLUSION Environmental carcinogenesis is the newest and one of the most ominous of
>••••••••••••••••••••••• the end-products of our industrial environment. Though its full scope and
extent are still unknown, because it is so new and because the facts are so
extremely difficult to obtain, enough is known to make it obvious that extrinsic
carcinogens present a very immediate and pressing problem in public and
individual health.
It should become one of the most urgent tasks of all medical men, public
health officials, labor and management leaders, and members of legislatures,
to become familiar with the problems of environmental cancer. They must
all work together to combat its causes at the source, before the dread disease
spreads to more and more of our people.
19
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