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AIR POLLUTION ASPECTS
OF
ORGANIC CARCINOGENS
Prepared for the
National Air Pollution Control Administration
Consumer Protection & Environmental Health Service
Department of Health, Education, and Welfare
(Contract No. PH-22-68-25)
Compiled by Douglas A. Olsen, Ph.D.
and James L. Haynes, M.S.
Litton Systems, Inc0
Environmental Systems Division
7300 Pearl Street
Bethesda, Maryland 20014
September 1969
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FOREWORD
As the concern for air quality grows, so does the con-
cern over the less ubiquitous but potentially harmful contami-
nants that are in our atmosphere. Thirty such pollutants have
been identified, and available information has been summarized
in a series of reports describing their sources, distribution,
effects, and control technology for their abatement.
A total of 27 reports have been prepared covering the
30 pollutants. These reports were developed under contract
for the National Air Pollution Control Administration (NAPCA) by
Litton Systems, Inc. The complete listing is as follows:
Aeroallergens (pollens) Ethylene
Aldehydes (includes acrolein Hydrochloric Acid
and formaldehyde) Hydrogen Sulfide
Ammonia Iron and Its Compounds
Arsenic and Its Compounds Manganese and Its Compounds
Asbestos Mercury and its Compounds
Barium and Its Compounds Nickel and Its Compounds
Beryllium and Its Compounds Odorous Compounds
Biological Aerosols Organic Carcinogens
(microorganisms) Pesticides
Boron and Its Compounds Phosphorus and Its Compounds
Cadmium and Its Compounds Radioactive Substances
Chlorine Gas Selenium and Its Compounds
Chromium and Its Compounds Vanadium and Its Compounds
(includes chromic acid) Zinc and Its Compounds
These reports represent current state-of-the-art
literature reviews supplemented by discussions with selected
knowledgeable individuals both within and outside the Federal
Government. They do not however presume to be a synthesis of
available information but rather a summary without an attempt
to interpret or reconcile conflicting data. The reports are
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necessarily limited in their discussion of health effects for
some pollutants to descriptions of occupational health expo-
sures and animal laboratory studies since only a few epidemio-
logic studies were available.
Initially these reports were generally intended as
internal documents within NAPCA to provide a basis for sound
decision-making on program guidance for future research
activities and to allow ranking of future activities relating
to the development of criteria and control technology docu-
ments. However, it is apparent that these reports may also
be of significant value to many others in air pollution control,
such as State or local air pollution control officials, as a
library of information on which to base informed decisions on
pollutants to be controlled in their geographic areas. Addi-
tionally, these reports may stimulate scientific investigators
to pursue research in needed areas. They also provide for the
interested citizen readily available information about a given
pollutant. Therefore, they are being given wide distribution
with the assumption that they will be used with full knowledge
of their value and limitations.
This series of reports was compiled and prepared by the
Litton personnel listed below:
Ralph J. Sullivan
Quade R. Stahl, Ph.D.
Norman L. Durocher
Yanis C. Athanassiadis
Sydney Miner
Harold Finkelstein, Ph.D.
Douglas A. Olsen, Ph0D.
James L. Haynes
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The NAPCA project officer for the contract was Ronald C.
Campbell, assisted by Dr. Emanuel Landau and Gerald Chapman.
Appreciation is expressed to the many individuals both
outside and within NAPCA who provided information and reviewed
draft copies of these reports. Appreciation is also expressed
to the NAPCA Office of Technical Information and Publications
for their support in providing a significant portion of the
technical literature.
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ABSTRACT
Epideitiiological studies indicate that air pollution
may play a role in lung cancer induction. Certain organic
carcinogens, normally present in polluted air, particularly
benzo(a)pyrene, have been shown to increase tumor incidence
in experimental animals. In addition, animal studies indi-
cate that other organic compounds may have synergistic or
antagonistic effects. No information has been found on the
effects of organic carcinogens on plants or materials.
Organic carcinogens fall into three main categories—
polynuclear aromatic hydrocarbons, polynuclear heterocyclic
and oxygenated compounds, and alkylating agents. The
major emission sources of organic carcinogens, particularly
of polynuclear aromatic hydrocarbons, are heat-generation
sources, such as burning coal, oil, and gas; refuse burning;
motor vehicle exhaust; and industrial processes. Of these,
heat generation accounts for more than 85 percent of the
polynuclear aromatic hydrocarbons generated, while the other
three sources each account for about 5 percent of the total.
In 1966, the average ambient air concentration of
benzo(a)pyrene in the United States was approximately 0.003
ug/m3 for urban areas and 0.0003 ug/m3 for nonurban areas.
Data indicate that benzo(a)pyrene represents only a small
percentage of the total amount of polynuclear aromatic hydro-
carbons found in the atmosphere.
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Abatement methods for organic carcinogens are
presently being studied under the hydrocarbon control pro-
grams.
The costs of premature death and the associated
costs of treatment and burial for lung cancer ascribable to
air pollution have been estimated. No information has been
found on the economic costs of the abatement of organic
carcinogen air pollution.
Methods of analysis are available which involve the
use of extraction and chromatographic techniques for separa-
tion of the compounds followed by analysis with spectral
methods.
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CONTENTS
FOREWORD
ABSTRACT
1. INTRODUCTION 1
1.1 Types of Organic Carcinogens 3
1.1.1 Polynuclear Aromatic Hydrocarbons (PAH) 3
1.1.2 Polynuclear Heterocyclics and
Oxygenated Compounds 8
1.1.3 Alkylating Agents 8
1.2 Organic Carcinogens as Cocarcinogens or
Anticarcinogens 10
2. EFFECTS 12
2.1 Effects on Humans 14
2.1.1 Particulate Matter 20
2.1.2 Particle Size 22
2.1.3 Irritants 25
2.1.4 Studies with Biological Material .... 26
2.2 Effects on Animals . 27
2.2.1 Commercial and Domestic Animals .... 27
2.2.2 Experimental Animals 28
2.2.2.1 Effects on Animal Tissue ... 39
2.3 Effects on Plants 40
2.4 Effects on Materials 40
2.5 Environmental Air Standards . . . 40
3. SOURCES 41
3.1 Natural Occurrence 41
3.2 Production Sources . . 42
3.3 Product Sources 47
3.4 Environmental Air Concentrations 51
4. ABATEMENT 53
5. ECONOMICS • 55
6. METHODS OF ANALYSIS • 59
6.1 Sampling Methods 59
6.2 Extraction Methods 59
6.3 Separation 61
60 3.1 Column Chroma to graphy 61
6.3.2 Thin-Layer Chromatography 64
6.3.3 Gas Chromatography 66
6.3.4 Other Techniques 66
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CONTENTS (Continued)
6.4 Analysis 67
6.4.1 Spectral Methods 67
6.4.2 Other Methods 68
7. SUMMARY AND CONCLUSIONS 71
REFERENCES
APPENDIX
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LIST OF FIGURES
1. Retention of Particulate Matter in Lung in Relation
to Particle Size 23
2. Benzo(a)pyrene Pyrosynthesis 99
3. Pathways for the Pyrosynthesis of Benzo(a)pyrene . 100
4. Carcinogenic Polynuclear Aromatic Hydrocarbons
Identified in Urban Air 101
5. Aza-Heterocyclics and Polynuclear Carbonyl
Compounds Identified in Urban Air 102
6. Reaction Pattern Showing the Products of
Decomposition of Unsaturated Hydrocarbons 103
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LIST OF TABLES
1. Carcinogenicity and Anticarcinogenicity of Some
Compounds Present in Polluted Air 7
2. Resource Costs Per Year of Diseases Associated
With Air Pollution 58
3. Summary of Recent Investigations in Spectral
Methods 69
4. Tumor Induction in Mice Following Cutaneous
Administration of Organic Extracts of Particulate
Atmospheric Pollutants 104
5. Tumor Incidence Following Injection of Organic
Atmospheric Pollutants to Neonatal Mice 106
6. Estimated Annual Benzo(a)pyrene (BaP) Emissions For
the United States 107
7. Benzo(a)pyrene Concentrations in Urban Sampling
Sites for January Through March 1959 110
8. Polynuclear Hydrocarbon Content of Particulate
Matter for Selected Cities 113
9. Seasonal Effect on the Benzo(a)pyrene
Concentrations of Various Urban Atmospheres .... 114
10. Concentrations of Benzo(a)pyrene in the Ambient
Air, 1966 115
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1. INTRODUCTION
According to some estimates,-1-2'108'1^8 the mortality
rate from lung cancer has increased about 30 times since
1900. This alarming increase has occasioned studies concern-
ing the cause of cancer. A portion of the organic material
present in the atmosphere, generally as suspended particulates,
has been identified as carcinogenic to experimental animals.
These organic carcinogens have been identified in the atmo-
sphere of virtually all large cities in which surveys have
been conducted. It is true, however, that in no case has a
suspected organic carcinogen been demonstrated to produce
lung cancer in humans.
i ftft
According to Sawicki, the composition of the urban
atmosphere is as yet (1967) undetermined, the vast majority
of the constituents being unknown. Certain organic compounds
present as particulates in the atmosphere have been identified,
and several of these have been found to be carcinogenic to
animals. There is also evidence that other organic compounds
may be carcinogenic.
Although there is some question as to the carcinogenicity
of selected compounds (such as those marked with an asterisk),
the major classes of organic carcinogens are as follows:
Polynuclear Aromatic Hydrocarbons (PAH)
Benzo (a)pyrene (BaP)
*Benzo (e)pyrene
Benz(a)anthracene
Benz(e)acephenanthrylene
Benzo (b) f luoranthene
-------
Benzo(j)fluoranthene
*Chrysene
Dibenzo(e,1)pyrene
Dibenzo(a,h)pyrene
Indeno(l,2,3-cd)pyrene
1,2-Benzanthracene
Polynuclear Aza-Heterocyclic Compounds
Dibenz(a,h)acrid ine
Dibenz(a,j)acridine
Polynuclear Imino-Heterocyclic Compounds
Polynuclear Carbonyl Compounds
*7H-Benz(de)anthracen-7-one
*Alkylating Agents
Aliphatic and olefinic epoxides
Peroxides
Lactones
The carcinogenicity of the above organic compounds
has been established through laboratory experimentation by
many investigators. It should be noted that, in many ex-
periments, A-strain mice particularly susceptible to tumor
development were used, and only in two studies was inhalation
used as the route of administration.125
The presence of substituent groups, particularly
alkyl groups, on some of these or other PAH compounds can
cause a profound change in their carcinogenic activity.1^8
Thus, while both benz(a)acridine and benz(c)acridine are
inactive when placed on the skin of mice, their 7-methyl
derivatives are very active (rated similar to BaP in carcino-
genic activity).228 Some of the other methyl derivatives of
228
these two compounds are also active. Furthermore, whereas
chrysene was found inactive on the subcutaneous tissue of
mice, the 4-, 5-, and 6-methyl derivatives were all active.
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The major source of atmospheric organic carcinogens
is the incomplete combustion of organic matter.9^ A secondary
source is the photochemical decomposition of noncarcinogenic
organic compounds into more active compounds. Incomplete
combustion, which generates organic carcinogens, occurs in
the process of heat generation, refuse burning, operation of
motor vehicles, and several industrial processes. Of the
compounds generated, the most extensively studied are the
polynuclear aromatic hydrocarbons (PAH), particularly benzo(a)-
pyrene (also known as 3,4-benzopyrene or BaP), which is con-
sidered the carcinogen most active to animals. Much of the
literature pertaining to the air pollution aspects of organic
carcinogens concentrates on the compound BaP, due in part to
its high relative carcinogenicity, and also in part to the
fact that its identification and quantitative determination
in air are relatively simple. Information concerning the
other known or suspected carcinogens is limited or nonexistent,
and in the words of Sawicki,-1-88 "We have no knowledge as to
whether the members of this great number of unknown trace
chemicals are innocuous, beneficial, or harmful to life in
the concentrations at which they are present in the various
nonurban, industrial, and urban atmospheres."
1.1 Types of Organic Carcinogens
1.1.1 Polynuclear Aromatic Hydrocarbons (PAH)
The majority of polynuclear aromatic hydrocarbons
(PAH) in our environment evolve from high-temperature
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4
reactions under pyrolytic conditions during incomplete
combustion of organic matter. The formation of PAH during
such processes occurs in two distinct types of reactions,
pyrolysis and pyrosynthesis. At temperatures above 400° to
500°C, organic components are partially cracked into smaller,
unstable molecules (pyrolysis). These fragments, mostly
radicals, recombine into larger, thermodynamically favored
and relatively stable PAH and heterocyclic hydrocarbons
(pyrosynthesis).103
Badger and his co-workers have studied the pyro-
synthesis of PAH.-1-0' I1 Their original working hypothesis is
illustrated in Figure 2 in the Appendix. From these data
and from information acquired by other investigators,
the following concept has been formulated: the temperature
that exists during the burning of organic matter easily
breaks single carbon and carbon-hydrogen bonds to yield free
radicals. These radicals combine and are dehydrogenated to
form aromatic ring systems that are relatively stable; only
the carbon-hydrogen bonds of these components are broken to
any significant extent. Long-chain paraffins, widely found
in fuels and plants, serve as special precursors of PAH.
Badger's original concept of PAH formation was verified by
extensive, carefully designed and carefully executed experi-
ments utilizing l^C-labeled precursors. Figure 3 in the
Appendix summarizes the steps of BaP pyrosynthesis as they
are suggested from the experimental findings. This concept
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can be extended to include hydrocarbons with uneven carbon
pc
numbers since methane also serves as a precursor of PAH.
Pyrolysis experiments like these were conducted in
a nitrogen atmosphere and have been criticized for not
accurately reflecting the conditions that prevail during
the actual burning of organic matter. As Hoffmann and
Wynder 3 point out, the fact remains that these studies
agree qualitatively with actual burning conditions of
organic matter, and the cited studies were conducted primarily
to discover the major precursors and pathways for the pyro-
synthesis of PAH rather than to compile quantitative data on
pyrosynthesis.
In studies of actual burning of organic matter, a
reducing atmosphere exists around and/or inside the burning
cone, as well as inside the combustion chamber. Newsome and
Keith-*--^ found this type of reducing atmosphere in the inner
cone of a cigarette, where it consists partially of hydrogen
(8.2 volume percent), carbon monoxide (11.8 percent), and
methane (1.3 percent), and contains only traces of oxygen
(1.4 percent). Gasoline engine exhaust gases generated
during idling may contain up to 18 volume percent carbon
monoxide, 2 percent volatile hydrocarbons, and traces of
hydrogen. The concentrations of carbon monoxide, methane,
and hydrogen and the absence or very low concentrations of
oxygen in the combustion products indicate the existence of
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a reducing atmosphere around and/or inside the flame or
combustion chamber. A reducing atmosphere is essential for
pyrosynthesis of PAH.
As indicated in Figure 3 in the Appendix, other PAH
can be formed by the preceding mechanisms. Long and his
145
co-workers at the University of Birmingham have also shown
that many PAH are formed during incomplete combustion of
ethylene and ethane. The structures of several representa-
tive PAH which have been identified in urban air are shown
in Figure 4 in the Appendix. Not all of the PAH, however,
are carcinogenic (see Table 1).
In addition to the PAH in our environment that envolves
from incomplete combustion of organic matter, a small portion of
it may derive from thermic or catalytic cracking of organic
components. The chemical mechanisms leading to the forma-
tion of trace amounts of PAH by cracking are similar to those
occurring during incomplete combustion.
PAH occur in the atmosphere primarily as adsorbed
compounds on soot particles. The biological effect of the
carcinogenic agents is critically related to the physical
characteristics of the particle. Particle size primarily
determines the extent of penetration into the tracheobronchial
tree.119' ^ To a great extent, particle size also governs
the rate and extent of the elution of carcinogenic hydro-
carbons from the soot particles on which they are adsorbed.
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TABLE 1
7
CARCINOGENICITY AND ANTICARCINOGENICITY OF SOME
p o i I 7
COMPOUNDS PRESENT IN POLLUTED AIR
Carcinogenicity Anticarcinogenicity
Compound Ref. 117 Ref. 28 Ref. 28
Benzanthracene + + +
Benzo(e)pyrene + - +
Benzo(a)pyrene +++ +++
Anthanthrene - - -
Perylene _ _ +
Benzo(g,h,i)perylene - - -
Benzo(k)fluoranthene - +
Benzo(b)fluoranthene ++ ++
Benzo(j)fluoranthene ++
Fluoranthene - -
Indeno(l,2,3-cd)pyrene +
Anthracene - +
Phenanthrene
Pyrene - - +
Benz(m,n,o)fluoranthene - +
Chrysene + + +
Benzo(c)acridine + +
Benzo(a)fluorene - +
Fluorene
Coronene - - -
Benz(a)carbazole + +
2-Naphthol - -
Inactive: -; weakly active: +; moderately active:
++; strongly active: +++.
Carcinogenic properties may be due to the impurity
5H-benzo(b)carbazole present in "commercial pure" chrysene.
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8
See Section 2.1.2 for further discussion of particle size.
1.1.2 Polynuclear Heterocyclics and Oxygenated Compounds
Large quantities of aza-heterocyclic compounds are
found in the compounds contained in some air pollution source
effluents, "' in very low concentrations in automotive ex-
haust fumes, and in moderate concentrations in the air.214
188
Sawicki states that many of these compounds and some others
have never been tested for carcinogenic activity; dibenz(a,h)-
acridine and dibenz(a,i)acridine (see Figure 5 in the Appendix),
however, are carcinogenic. Many polynuclear carbazoles have
been found to be carcinogenic. 4 In general, however, informa-
tion is scanty in this area.
In regard to polynuclear carbonyl compounds, Hoffmann
•I QO
and Wynder note that, in theory, many known nonvolatile
"oxygenated substances" may exist in our respiratory environ-
ment. However, very few chemical studies concerning these
compounds have been reported. This is surprising, since
many neutral "oxygenated" compounds have been found in
287
tobacco smoke.
The paucity of chemical data in this area may be a
consequence of a lack of biological information on the sub-
fractions containing oxygenated substances.
1.1.3 Alkylating Agents
Common alkylating agents found in the atmosphere
include epoxides, peroxides, and lactones.
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Certain epoxides and peroxy compounds have been shown
1 9 2
to be carcinogenic, ' as well as to have other
I I Q
physiological effects. A recent source of these types of
compounds is the universal use of liquid fuels, such as
gasoline and diesel fuel, in the internal combustion engine. '
In the unburned state, these liquid fuels are highly reactive
and when volatilized, undergo oxidation in the presence of
oxides of nitrogen in a photochemical reaction. The reaction
products consist of a broad group of peroxides, including
compounds with epoxidic linkages. The unburned gasoline and
other exhaust products emitted from automobiles contain
significant quantities of ethylehe, propylene, butene, and
other unsaturated hydrocarbons. Under certain meteorological
conditions, these vapors react in the presence of sunlight
and oxides of nitrogen to form a broad spectrum of hydro-
carbon oxidation products.
Interest in compounds belonging to this group has
centered primarily around the formation of epoxides because
of the demonstrated carcinogenic potency of certain classes
of these compounds .
Sato and Cvetanovic studied the decomposition of
unsaturated hydrocarbons; the products of decomposition
following photochemical reaction include compounds with
epoxidic linkages. A typical reaction is shown in Figure 6
in the Appendix. These reactions account for the major de-
composition products, which include formaldehyde and acetone
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10
as well as epoxides. Some of the latter compounds belong to
the group of experimentally verified carcinogens. Apparently,
significant quantities of epoxides are produced.
The concentration of hydrocarbons in the air from
auto exhaust is about 3.4 ppm. Of this amount, 1 ppm is
made up of saturated hydrocarbons, and the remainder consists
of olefins associated with 0.05 ppm diolefins. Ethylene,
constituting half of the olefins produced, is of special
significance. When the automotive exhaust is exposed to
light and air.- photochemical reactions occur which destroy
56 percent of the total amount of hydrocarbons in a 2-hour
interval. Two-thirds of the hydrocarbons which are destroyed
are olefinic (excluding ethylene), i.e., olefins which are
known to give a 17 percent epoxide yield. Thus, 6 percent
of the total hydrocarbons emitted from the exhaust are trans-
formed to epoxides of the type that have been found to be
28
carcinogenic to experimental animals. The controlled
reaction is equivalent to 2 hours of exposure to photochemical
reactions that occur naturally in the Los Angeles atmosphere.
The epoxide concentrations determined are conservative.119
1.2 Organic Carcinogens as Cocarcinogens or Anticarcinogens
Little information is available regarding the syner-
gistic or antagonistic effects of organic carcinogens. How-
ever, the limited animal studies available have demonstrated
that organic carcinogens do play a role as cocarcinogenic
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11
or anticarcinogenic agents. There are data that suggest
that phenols and some long-chained hydrocarbons are co-
carcinogenic. '
Table 1 in Section 1.1.1 shows some PAH that were
reported by Kotin and Falk121 to have anticarcinogenic
activity. These authors also presented data that demonstrated
that the carcinogenic properties of dibenz(a,h)anthracene, a
strong carcinogen, can be strongly inhibited by the dihydro-
and the hexahydro-derivatives of dibenz(a,h)anthracene, as well
as with benz(a)anthracene and phenanthrene. Several other
authors have reported that a weak carcinogen or noncarcinogen
can inhibit the activity of normally potent chemically
related carcinogens.40'126'132'237
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12
2. EFFECTS
According to Pybus, cancer has puzzled mankind
since it was first recognized in the fourth century B.C.
The first and most important observation of its cause was
made by a London surgeon, Percival Pott, who in 1775 des-
cribed cancer of the scrotum in chimney sweeps; he decided it
resulted from the soot lodged in the crevices of the skin
of the male genitals. This apparent causal relationship
between soot and skin cancer led to attempts to produce
cancer in animals by painting tar on their skin. The
earliest experiments, performed about 1889, failed because
they were conducted on resistant animals or because not
enough time was allowed for the cancer to develop. Thus, the
demonstration that soot or tar was actually responsible for
this form of cancer remained unproved until 1915, when skin
cancer was produced in a rabbit by means of repeated applica-
tions of extracts of tar.16^
After World War I, British investigators, under the
leadership of Sir Ernest Kennaway, demonstrated by persistent
and tedious experimentation that skin cancer could be induced
in mice by coal tar. Fractionation of the tar to isolate the
active ingredients led to the discovery that the tumor-produc-
ing constituents were also highly fluorescent. Thus, examina-
tion of fractions for fluorescence guided the separations
rather than lengthy animal tests, and rapid progress was
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13
made. A discovery followed shortly: certain PAH, such as
the now familiar BaP contained in the tar are responsible in
part for the tar's carcinogenic effect.
Numerous studies have demonstrated a worldwide
increase in the frequency of and mortality from lung cancer.
These investigations leave little doubt that the apparent
increased incidence of lung cancer is both real and, at least
until very recently, progressive. Interest in this lung
cancer increase has sparked many biological and medical
investigations. Some of the studies have been concerned with
the effect of air pollution and/or smoking. Many of the stud-
ies relating air pollution to cancer in humans are epidemio-
logical. As already noted, airborne carcinogens have been
the subject of considerable study in the laboratory.
Although cigarette smoking has been a widely publi-
cized issue for more than a decade, it is generally agreed,
however, that a history of cigarette smoking is causally
related to the risk of developing lung cancer. Any meaningful
discussion of the relation of lung cancer to cigarette smoking
is clearly beyond the scope of a survey directed toward
national air pollution control. A review of this subject by
Rigdon and Kirchoff covers the years 1930 through 1960.
More recent articles have dealt with the chemical composition
235 288
of tobacco smoke, ' the mechanism of carcinogenic action
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14
*7 1 O O £\
of tobacco smoke, smoking and oral cancer, smoking and
174
cancer of the lung, smoking and cancer of the urinary
tract, and retention of cigarette smoke by the lungs.43
In addition, the U.S. Public Health Service has issued over-
95 232
all views of smoking and health. '
{
A related area which is pertinent to this survey is
the impact of smoking as compared with air pollution on
development of lung cancer. The reports seem to indicate
that the joint effect of cigarette smoking and air pollution
is additive rather than multiplicative; however, the evidence
is still inconclusive.23'24'247'285
2.1 Effects on Humans
Although no suspected organic carcinogen has been
O
proved experimentally to cause lung cancer in humans,
an apparent association has been shown between air pollution
and human mortality rates from lung cancer. Furthermore,
organic carcinogens have been shown to increase tumor
activity in experimental animals. Data on experimental
animals is presented in Section 2.2.
The increase in the absolute mortality resulting from
cancer (especially of the lung) has been demonstrated in vari-
ous parts of the world during the past half century. Kotin
119
and Falk indicated that this increased mortality has been
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15
characterized by the following: (1) greater susceptibility to
lung cancer in urban than in rural residents; (2) greater
incidence among individuals with a history of prolonged and
excessive cigarette smoking; and (3) greater frequency of lung
cancer in males than in females.
The increased incidence of lung cancer parallels the
introduction of new etiological agents into the respiratory
environment around the turn of the century. Since lung
cancer, as other neoplasms, is not likely to result from a
single initiating or promoting experience, it is important to
evaluate the pathogenic significance of polluted air. This
evaluation is necessary both for the detection of carcinogens
and the determination of the role of air pollution in relation
119
to other environmental factors.
...... 37,42,49,51,60,61,88,102,119,
Numerous investigations
128,162,222,242,285,289 , . ,. . , , . , ., _
' have indicated a higher incidence of
lung cancer for urban residents than for rural residents.
55,56,87,88,153,219,284
Studies relating smoking to lung cancer
also show the so-called "urban factor." After correcting for
the differences in smoking habits between urban and rural
residents in the United States, the rate of lung cancer was
88
still 25 percent lower in rural areas.
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16
The nature and significance of the urban effect have
not been specifically established. It may result from occu-
pational differences, from rural patients' habit of obtaining
improved medical care in the city and reporting as urban resi-
dents, from improved accuracy of cancer reporting in urban
areas, or from a combination of these and other factors.
22
In 1964 Buck and Wicken reported an association
between the degree of air pollution and the incidence of
lung cancer and bronchitis mortality in two areas of the Eston
294
(England) urban district. However, Zeidberg .et. aJ._. reported
(also in 1964) on a study of 9,313 individuals in Nashville,
Tenn., in which they found no evidence of a relationship
between air pollution and cancer morbidity rates.
Nevertheless, exposure to polluted air is a widely accepted
explanation for the consistent observation of increased lung
cancer incidence in urban populations. Epidemiological,
physicochemical, and biological data are consistent with an
etiological role for polluted atmosphere.
121
Kotin and Falk cite the following evidence to support
the contention that air pollution may be a significant factor
in the pathogenesis of lung cancer:
(1) Carcinogenic agents have been identified and
quantified in the polluted air of essentially every city in
which they have been sought;
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17
(2) Similarly, chemical compounds with known tumor-
promoting properties have been identified and quantified in
polluted urban air;
(3) The stability and survival of carcinogenic hydro-
carbons in the atmosphere are compatible with inhalation and
a postulated biological effect in those exposed;
(4) Carcinogenic agents, as well as noncarcinogenic
respiratory epithelial irritants, occur in the atmosphere in
a state compatible with host entry and tracheobronchial
deposition;
(5) Alteration in function and structure of the respir-
atory epithelium of representative mammalian species has been
demonstrated following exposure to a broad spectrum of these
environmental irritants. The resulting changes appear to
facilitate the biological action of carcinogenic agents; and,
(6) Bioassay by skin-painting and subcutaneous-injection
techniques has established the carcinogenic properties of com-
pounds identified in and extracted from polluted air. Exposure
of both susceptible and resistant strains of mice to aerosols
of synthetically reproduced polluted urban air has resulted
in lung tumors in both strains.
^ . . ^ 5,49-51,61,62,85,
Epidemiological studies of immigrants
' indicate that air pollution may be an etiological factor
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18
which has long-term residual effects with a latent period of
induction. British immigrants to South Africa had a higher
incidence of mortality from lung cancer than the native white
South Africans, who smoked even more than the immigrants. '
This was observed in British immigrants who had resided in
South Africa even for 20 or more years. Similar studies indi-
cate that immigrants to New Zealand, ' Austria, Israel,
148
and Mexico showed a greater pattern of lung cancer than was
found in their new area of residence. In contrast, Norwegian
immigrants who moved to the United States, where the air
pollution was greater than in their home country, had a cancer
rate higher than native Norwegians but less than the native
85 86
Americans. It has been further observed in the United States
that rural residents who previously resided in an urban area
for 10 years or more had a greater risk of lung cancer, inde-
pendent of the smoking history than the corresponding rural
residents who had no urban exposure.
In a recent report based on epidemiological findings,
Stocks hypothesized that air pollution accelerates the
final stages of cancer growth in susceptible persons who have
reached an advanced point in the latent interval of the
disease.
-------
19
Attempts have been made to correlate the amount of
atmospheric BaP pollution with the development of lung cancer.
248
Stocks and Campbell observed a higher incidence of lung
cancer among persons living in an area in which BaP was known
221 222 244245
to be present in the atmosphere. Shahab, ' Stocks,
83
and Gorman observed a relationship between the increased
mortality from lung cancer and the concentration of carcino-
genic PAH in urban areas.
188,217
In contrast, Sawicki et al. in several studies
have not been able to demonstrate a correlation between lung
188
cancer death rates and the amount of atmospheric BaP- Sawicki
suggests that because airborne carcinogens are so numerous,
many have not yet been identified. He further states, "The
number and type of carcinogens found in the atmosphere indicate
that attempts to correlate carcinogenicity of the mixtures in
our chemical environment with concentrations of BaP are probably
naive in most cases and spring from our lack of knowledge of
the composition of the mixtures with which we are dealing."
109
Hueper et al. were unable to find a correlation in a com-
bined analytical and experimental bioassay study using samples
of polluted air from eight metropolitan centers in the United
States.
It is now generally accepted that usually many factors
-------
20
are involved in the initiation and promotion of cancer.
Consequently, a correlation between the incidence of cancer
and any single suspected environmental factor is extremely
difficult to establish as well as quite limited in usefulness.
2.1.1 Particulate Matter
The occurrence of gastric cancer has been linked with
the presence of suspended particulate matter in the atmosphere.
Anderson and Coffey hypothesized that the causative agent of
gastric cancer is associated with soot, winkelstein and
43
Kantor have found that mortality rates from gastric cancer
in a selected population were twice as high in areas of high
suspended particulate air pollution as in areas of low pollu-
tion in a northeastern United States industrial area. The
exact nature of the particulate was not specified; however/
in areas of high industrial air pollution, soot is usually
295 296
a significant constituent. In a Nashville study, '
soiling indices were found to correlate directly with mor-
tality from stomach cancer and with prevalence of bladder,
esophagus, and prostate cancers. No clear correlation was
found between soiling indices and mortality from lung,
bronchial, or large intestinal cancer.
144
In 1963, Litvinov et al. studied the relationship
between pulmonary cancer in man and air pollution resulting
from the discharge of carcinogens by aluminum plants. Over
10 kg of BaP were discharged into the air daily resulting in
-------
21
the deposit of an average of 9.1 ug per square mile per day
of this material on the ground in the area of the plant.
These high concentrations of BaP were implicated as a cause
of chronic morbidity of the respiratory tract.
Konstantinova and Chertova studied the effect of
dust and other airborne contaminants on lung cancer morbidity.
Two population districts of Ufa in Russia were studied. The
first area was located between two petroleum refineries and
the other was situated 20 kilometers from the refineries. The
symptoms characteristic of chronic hydrocarbon poisoning were
observed more than three times as often in the population near
the refineries than in the one 20 kilometers away. The lung
cancer mortality rates per 10,000 population were 0.8 for the
noncontaminated area and 1.28 for the contaminated area.
The carcinogenic properties of soot are believed to
248 271
result from the presence of certain adsorbed PAH. '
120
Kotin and Falk have studied the role of soot in lung cancer,
Their findings indicate that soot is a powerful carcinogenic
agent because of its ability to adsorb large quantities of
known carcinogens. In addition, certain physical properties
of the soot, such as particle size, facilitate transport into
the lungs and elution of these carcinogens by body fluids.
-------
22
2.1.2 Particle Size
PAH and other organic carcinogens are primarily pres-
ent in the atmosphere as adsorbed compounds on soot parti-
cles. The biological effect of the organic carcinogens is
critically related to the physical properties of the particle
on which it is adsorbed. Particle size largely determines the
extent to which particles can penetrate the tracheobronchial
tree. 2 Particles in the size range of 125 R to 2.5 |a are
of great biological importance. Particles larger than 2.5 p.
gaining host entry are largely retained in the mucous membranes
of the nose, oral cavity, pharynx, and nasal sinuses. Parti-
cles less than 125 A remain largely suspended in the circu-
lated air, and thus pulmonary retention of these particles is
rather small. The pulmonary retention of particulate matter
by the lung in relation to particle size has been given by
47
Dautrebande et al. Figure 1 shows the relationship between
retention of particulate matter and particle size.
The size of the particulates on which the carcinogenic
hydrocarbons are adsorbed also determines the rate and elution
70 236
of the hydrocarbons from the particles. Steiner, using
commercial carbon blacks, was able to relate the skin carcino-
genic activity of adsorbed carcinogens to the size of the soot
particle and to the presence of natural eluting substances in
-------
23
Retention
80
70
60
50
40
30
20
10
.25 .50 .75 1.0
2.0 3.0 4.0
Particle size (microns)
5.0
FIGURE 1
Retention of Particulate Matter in
Lung in Relation to Particle Size47
-------
24
the skin at the point of deposition. He concluded, "The
principles of natural and conditioned carcinogens, of solvent
elution, and of adsorption are advanced to explain some clini-
cal and epidemiological observations on human skin and lung
cancers, and on the role of preceding pathological lesions in
predisposing to pulmonary tumors." It has been suggested that
the solvent action of lipids and sebaceous secretions on the
skin exerts an eluting effect by liberating the carcinogenic
PAH from the soot particle.
In chemical studies of soot recovered from human lungs
during autopsy, Falk et al. could not demonstrate the presence
of BaP, although traces of pyrene were detected. It was possi-
ble, however, to demonstrate experimentally the entry of soot
particles of appropriate size into the cells of the respira-
tory tract of mice, rats, and rabbits, both by histological
studies and by the fluorescence of BaP (using fluorescence
120
microscopy techniques). It then became necessary to deter-
mine the effect of cellular and plasma proteins on the elution
of PAH from soot. It was found that PAH is readily eluted
from commercially prepared soot particles of 0.5 microns.
When the particle size population was mixed, the liberated
PAH from the larger particles was adsorbed by the smaller
o
particles. Thus, particles of less than 800 A in diameter
-------
25
do not yield PAH in the presence of physiological eluting
agents. Instead, they serve as scavengers for the readsorption
of the PAH eluted from larger particles.
2.1.3 Irritants
In addition to the normally recognized carcinogens,
other organic compounds usually present in polluted urban air
may act as irritants to the respiratory system, triggering
physiological responses. These responses may result in the
formation of malignant tumors or render the system more sus-
ceptible to the usual pathogenic effects of substances generally
recognized as carcinogens. Irritants in the respiratory envi-
ronment can interfere with ciliary activity and the flow of
the mucous stream in such a way that particulate matter accumu-
lates on the underlying cells. The typical response of ciliated
mucous-secreting epithelium to irritant aerosols is character-
ized by a small increase in the rate of flow, followed by a
slower flow rate that eventually returns to normal. The bio-
logical effect of the alterations in the rate of mucous flow
is one of increased particle retention, enhancing the oppor-
tunity for tumor formation. This phenomenon represents a
step in the pathogenetic sequence in which compounds that are
not in themselves carcinogenic appear to facilitate the bio-
logical activity of compounds capable of inducing cancer in
-------
26
119
the respiratory tract.
Among the compounds normally present in polluted
urban air implicated as irritants are: formaldehyde, acet-
aldehyde, acrolein, propionaldehyde, formic acid, acetyl
peroxide, peracetic acid, propylene oxide, and cyclohexene
oxide.68
2.1.4 gtudies with Biological Material
Cultures of human fetal lung tissue were exposed to
41
BaP by Lasnitzki, and to fractions of cigarette smoke con-
136 135
densate by Lasnitzki and Kennaway and by Lasnitzki alone.
Basal cell hyperplasia and metaplasia of the epithelium, pro-
liferation of bronchial units, and suppression of mesenchymal
elements occurred during 2 or more weeks of cultivation under
continuous exposure to BaP. A hydrocarbon-free fraction of
cigarette smoke condensate was also active (producing squamous
metaplasia), indicating that the effects of the condensate
could not be attributed to hydrocarbons alone.
179
Rounds et al. demonstrated that an established line
of human conjunctival cells show an increased growth rate and
undergo increased chromosomal aberrations when treated with
chloroform extracts of automobile exhaust. He also showed
that 3-methyl-4-dimethyl-amino-azobenzene induced the following
changes in human conjunctival cells in a suitable growth
-------
27
medium: growth stimulation, increased chromosomal stickiness
and scattering during mitosis, and a decrease in a positive
178
staining reaction for phospholipids.
Allison and Mallucci demonstrated that the carcinogens
BaP and 9,10-dimethyl-l,2-benzanthracene (DMBA) are concentrated
by the lysosomes. The genetic perpetuation of carcinogen-induced
metabolic changes has been explained on the basis of specific
ICO
disruptions in metabolic regulatory circuits. Experiments
which purported to show an intercalation (mutagenic interaction)
between carcinogens and deoxyribonucleic acid (DNA) have been
7R
criticized by Giovanella. °
106
Hsu _et al. described the inhibitory effect of certain
carcinogenic aromatic hydrocarbons on the replication of single
stranded ribonucleic acid (RNA) and DNA. Hsu et al. later
demonstrated the inhibition of viral nucleic acid and protein
synthesis in Escherichia coli by DMBA.
2.2 Effects on Animals
2.2.. 1 Commercial and Domestic Animals
No information is available concerning the effects of
organic carcinogens on commercial and domestic animals. How-
ever, Pybus reports that virtually every form of benign or
malignant tumor has been found among domestic animals. Cancers
of the mouth, throat, breast, and other body parts are
-------
28
relatively common among older cats and dogs.
240
Stewart examined 36 wild mammals and birds from
the Philadelphia Zoo for pulmonary cancer, pulmonary adeno-
matosis, and squamous metaplasia. Histologic material
available on 31 of the animals indicated: adenocarcinomas
in 11 birds of the family Anatidae, a silver pheasant, a
red jungle fowl, and a coypu; squamous cell carcinoma in a
North American otter; undifferentiated small-cell carcinoma
in a Java sparrow; alveologenic carcinoma in a striped skunk;
pleural mesotheliomas in a Cape hunting dog and a clouded
leopard; adenomatosis, squamous metaplasia, or both in a red
fox, puma, North American otter (which also had squamous cell
carcinoma of the lung), squirrel monkey, peafowl, African
eared vulture, Chinese myna, 2 toucan barbets, and a
rabbit-eared bandicoot; tuberculosis in a civet; pneumonia
in a kangaroo; and metastatic renal carcinoma of the lung in
a red wolf.
2.2.2 Experimental Animals
The direct effect on animals of organic carcinogens,
normally present in polluted urban air, is difficult to
evaluate. Most of the information available on the effect of
organic carcinogens on animals has been obtained under experi-
mental conditions, which are different from the conditions
-------
29
which normally constitute the natural environment of the
animal.
There has been extensive investigation of the effects
on experimental animals of specific compounds that pollute
the atmosphere. Much of the work has utilized skin painting
97 28
with extracts of chimney soots, road dusts, and vehicular
exhausts,104'124 or injections of these extracts.109'125'140'141
In general, inhalation studies have not attained the same
degree of success as those using painting and injection
techniques. The induction of bronchogenic carcinomas in
experimental animals has often required such drastic treat-
ments as transfixion of the lungs with carcinogen-impregnated
threads, intrabronchial implantation of wire pellets
impregnated with carcinogens, and the use of radioactive
134
materials.
In recent years, successful production of experimental
lung cancer has been reported through use of the following
test compounds or mixtures? "artificial smog" (ozone-treated
1 O C 1 "7 O 1 ft O 1 Q *3
gasoline vapor), ' BaP adsorbed on hematite, ' BaP
in polysorbate 80, an aerosol containing both ozonized-gaso-
123 281
line and influenza virus, ' and mixtures of phenolic and
O £\ "3
nonphenolic extracts of coal tars. The investigations of
Kotin and his co-workers, ' ' and of Tye and Stemmer,
-------
30
employed natural inhalation of the "polluted air," whereas
the other experiments used intratracheal instillation.
For test animals, investigators have often used a
strain of rodents that is genetically susceptible to "spon-
taneous" formation of the type or types of cancer being
studied.
The carcinogenicity of 14 mono-, di~, and trimethyl-
ated BaP was studied by Lacassagne et_ aJL_. using labora-
tory mice as test animals (three injections of 600 |jg each).
The majority of these compounds showed highly pronounced
sarcomagenic properties, both regarding the percentage (almost
100 percent) of animals developing tumors and the latency
period (100-150 days). Many of these homologues were more
active than nonsubstituted BaP. From this study, the authors
concluded that introduction of more than three methyl groups
into the BaP molecule would lead to a loss of carcinogenicity.
250
Stokinger and Coffin have discussed the importance
of the enhancement of organic carcinogen action (such as that
of BaP) with seemingly inert particles. Iron oxide in par-
ticular appears to have properties that possibly contribute
to cancer production. These authors cite the work of Saffiotti
180 181 184
et al., ' ' who produced a variety of malignant tumors
-------
31
in the lungs of hamsters. The animals were intratracheally
injected with a saline suspension of BaP ground together with
hematite (Fe20a) as a carrier dust in amounts equivalent to
3,000 ng of each chemical (a very high dose). Fifteen weekly
injections were given. Two important facts were revealed in
this study: a high incidence of lung cancer was produced,
up to 100 percent of the animals in some experiments; and
these lung cancers mimicked all the cell types seen in human
lung cancers, i.e., squamous cell carcinoma, anaplastic
carcinoma, adenocarcinoma, and even tracheal cancers. Dose-
response effects were indicated, as was the possibility that
a single high dose could induce cancers in the system. Ac-
181
cording to Saffiotti et al. the increased carcinogenic
action is due to the iron oxide, which penetrates the bron-
chial and alveolar walls into the lung tissue without extensive
damage or destruction of the ciliary and mucous barrier; the
iron oxide also acts as a vehicle to transport the carcinogen
airon oxide was chosen as the carrier dust because it has no
extremely irritating or toxic effects. Saffiotti believes
that in order to carry the carcinogen in high concentrations
to healthy cells, an inert carrier is required—that is, a
carrier which does not destroy the cells.
Benzo(a)pyrene alone has induced cancer in the lungs of exper-
imental animals, but usually with some difficulty and in low
yield.
-------
32
to the lung tissues. The carcinogen is then eluted from the
particulates and spreads diffusely throughout the tissue.
They surmise that the rate of removal of BaP from the respira-
tory tract is slowed by action of the inert dust as it is
stored in macrophages. Thus, the carcinogen remains in the
lung, unmetabolized in high local concentrations — an important
factor in producing cancer with BaP. They also suggest that
such a mechanism is a realistic concept of what actually
occurs in nature as man breathes the polluted air—i.e.,
carcinogens adsorb on iron oxide or other "inert" particles
which act as a vehicle to transport the carcinogens into the
lungs through the respiratory tract lining to the lung tissues,
where the carcinogens are eluted by the cell plasma. However,
it is yet to be shown that BaP is adsorbed onto iron oxide
particles in the atmosphere.
172
Rigdon and Neal studied the absorption and excre-
tion of BaP using ducks, chickens, mice, and dogs as test
animals. There was no apparent acute injury when large amounts
(e.g., 250,000 |ag for ducks) of BaP crystals and/or BaP sus-
pended in a physiologic solution of sodium chloride, with a
1 percent solution of polysorbate 80 were given orally to
ducks, chickens, mice, and dogs and intratracheally to ducks.
BaP was detected in the blood of ducks as well as in the blood
-------
33
and bile of chickens and dogs. The presence of BaP was also
detected in the skin of the chickens and mice. The mesenteric
tissue, the gallbladder and kidneys, and the urine of the
treated mice, as well as the kidneys of treated chickens and
ducks contained BaP.
173
Rigdon and Neal found that although white Swiss
mice (59 or more per group) fed commercial laboratory pellets
of BaP rarely had spontaneously occurring tumors in the stom-
ach, they did have spontaneously occurring pulmonary adenomas.
BaP crystals were added to the commercial ration in concen-
trations of 250 and 1,000 |J.g per gram of food and fed routinely
to the mice. Papillomas and squamous cell carcinomas in the
first portion of the stomach as well as an increase in the
number of pulmonary adenomas resulted. All the mice fed the
1,000 M-g BaP-containing ration for 86 days or longer developed
gastric neoplasms. When mice born of mothers fed BaP during
pregnancy and lactation were fed the control ration after
weaning, gastric tumors did not develop; however, littermates
fed BaP did develop such tumors.
154
These same investigators studied the growth of
young mice fed BaP- They found that the rate of increase in
weight of litters of young mice nursed by mothers fed BaP
was lower than that of litters from lactating mothers fed a
-------
34
normal ration. In some mice in the BaP-fed litter there was
a decrease in weight that began at 10 to 12 days of age. After
the young mice were weaned and fed a standard ration, their
weight still remained lower than normal. This diminution in
weight was attributed to a decrease in nutrition and not to a
toxic effect resulting from the BaP-
o a. T
Toth and Shubik investigated carcinogenesis in AKR
mice injected subcutaneously with BaP and dimethylnitrosoamine
(DMN). In contrast to controls, mice injected with BaP pro-
duced malignant lymphomas more rapidly; and they developed
lung adenomas. The DMN had no apparent effect on the develop-
ment of virally mediated lymphomas, but did cause both benign
and malignant liver tumors and lung adenomas.
Pylev investigated the effect of the dispersion of
soot on the deposition of BaP in the lung tissues of rats.
Two contrasting kinds of carbon black (soot) were administered
intratracheally: 5,000 |-ig channel black, with particles of 0.01 M-;
and 5,000 |j.g thermal decomposition black, with particles of
0.3 p.. He found that the coarsely dispersed decomposition
black promoted rapid disappearance of BaP from lung tissue,
whereas the finely dispersed channel black impeded the elimi-
nation of BaP and facilitated its decomposition.
Shahab .et a^.225 studied the importance of local
retention of carcinogenic agents in the pathogenesis of lung
-------
35
cancer in rats. In this experiment 280 animals were given
5,000 [ig BaP in suspensions of india ink in three doses by
intratracheal intubation. It was found that BaP retention
was a function of the number of administrations of BaP, as
the number of exposures to BaP increased, the retention in
the lung was found to increase.
1 a. C\
Tomingas found that the subcutaneous implantation
of starch-encapsulated soot on the back of rats resulted in
99
the formation of sarcoma in low yield. Herrold and Dunham
showed that repeated intratracheal instillations of BaP sus-
pended in polyoxyethylene sorbitan monostearate (Tween 60)
induced papillomas and carcinomas of the trachea, main-stem
bronchi, and bronchioles in Syrian hamsters. The mucosa of
the tracheobronchial tree showed both regenerative and atypical
epithelial changes. Neoplastic lesions were not induced in
another group of animals that received intratracheal instil-
227
lations of BaP dissolved in olive oil. Shubik reported
that bronchogenic carcinoma could be induced in hamsters by
using a colloidal suspension of 7,12-dimethylbenz(a)anthracene
administered by endotracheal intubation, but found that repeti-
tion of the study with BaP yielded uniformly negative results.
QO
Herrold studied the effects of BaP, cigarette smoke
condensate, and atmospheric pollutants on the respiratory
-------
36
system of Syrian hamsters. He observed that benign and
malignant tumors of the trachea, bronchi, and bronchioles
were induced following intratracheal instillation of BaP
suspended in Tween 60. Only atypical epithelial changes
suggestive of precancerous lesions were observed with BaP
suspended in distilled water. No significant changes were
noted in the animals that received intratracheal instillation
of BaP dissolved in olive oil. These findings suggest that the
vehicle for the carcinogen as well as the physical state of
the carcinogen are important factors in carcinogenesis.
The intratracheal instillation of cigarette smoke con-
densate and atmospheric pollutants in the hamsters produced
regenerative epithelial changes of the tracheobronchial mucosa.
These lesions included basal cell hyperplasia and peribronchial
and peribronchiolar proliferation. Atmospheric pollutants
induced extensive adenomatous proliferation involving large
areas of the lung in all of the test animals. No tumors of
the respiratory tract were induced either with cigarette smoke
condensate or atmospheric pollutants.
Bogacz and Koprowski investigated the comparative
carcinogenic properties of air pollutants, tobacco tar, and
BaP by means of correlated cytopathologic studies, utilizing
the uterine cervix of mice as a target organ. It was
-------
37
demonstrated that mice of the ZBG and C3H strains treated
intravaginally with air pollutants and tobacco tar developed
cellular abnormalities and histologic lesions that were
morphologically indistinguishable from those accompanying the
development of BaP-induced carcinoma.
The carcinogenicity of atmospheric pollutants in mice
has been demonstrated with organic extracts collected from
various sources, using various techniques (Table 4 in the
Appendix). When pollutant extracts are administered to mice,
whether by painting or by subcutaneous injection, local tumors,
papillomas, carcinomas, or sarcomas—sometimes accompanied by
multiple pulmonary adenomas—have generally resulted. Notable
exceptions were: (1) the high incidence of distant tumors,
hepatomas, and lymphomas, in addition to multiple pulmonary
adenomas; and (2) the virtual absence of local tumors following
subcutaneous injection of relatively small concentrations of
organic pollutant extracts in infant mice (Table 4 and 5 in
the Append ix).
I OO
Saffiotti et al_. ° reported that vitamin A prevented
development of tumors in hamsters. Syrian golden hamsters of
both sexes received 10 intratracheal instillations each of
BaP and hematite suspended in saline. One group received no
further treatment and developed 13 squamous tumors and 13 cases
-------
38
of squamous metaplasia in 53 exposed animals. One week after
the end of the BaP treatment, the second group began receiving
stomach tube feeding of vitamin A palmitate twice weekly (con-
tinued for life). In this group of 46 animals, only one de-
veloped a microscopic squamous tumor in the bronchus, while an-
other developed a patch of squamous metaplasia in the trachea. The
incidence of forestomach papillomas was also reduced markedly
by vitamin A treatment. The authors suggested that vitamin A
has a systemic inhibitory effect on the induction of squamous
changes (metaplasia as well as benign and malignant squamous
tumors) in the columnar mucous epithelium of the respiratory
tract.
In studying the influence of phenols in the production
O ^ O
of carcinomas, Tye and Stemmer exposed five groups of mice
(20 per group) to aerosols containing blends (120 lag/liter)
of coal tar extracts, including phenols. The mice were exposed
2 hours, three times weekly, for 55 weeks. Animals were sacri-
ficed at various intervals. The lungs and tracheas of all mice
were then examined grossly and microscopically for neoplasms
or relevant morphologic changes. After 46 weeks, among 32
survivors in two groups, which received similar aerosols con-
taining phenols, there were 4 cases of adenocarcinoma, 19 of
intrabronchial adenoma, and 10 of squamous metaplasia. In
-------
39
20 survivors of another group, which received the same tar
without phenols, there was no incidence of adenocarcinoma;
11 had intrabronchial adenoma and 2 had squamous metaplasia.
Gardner reported that laboratory mice exposed to
community photochemical smog levels for a 16-month period
showed a slight but statistically insignificant increase in lung
tumor development (adenoma) in ,the aging animals, when compared
with control animals that were exposed to filtered air.
2.2.2.1 Effects on Animal Tissue
41
Lasnitzki studied the effect of the carcinogenic
hydrocarbons 9,10-dimethyl-l,2-benzanthracene (DMBA), BaP, and
methylcholanthrene (MC) on organ cultures of suckling rat
trachea. It was found that these hydrocarbons caused loss
of differentiated tracheal epithelial cells and of mesen-
chymal elements (including chondrocytes), but not of basal
cells. The mitotic rate and the proportion of cells incorpo-
rating H -thymidine increased in response to hydrocarbons, but
the increase in H -thymidine uptake and mitotic rates was not
always proportionate, nor were these responses alike for all
hydrocarbons.
The effects of DMBA, BaP, and MC were similar in that
all produced clear-cut increases in the proportion of basal
cells undergoing DNA synthesis.
-------
40
In studying the effect of MC on prostate glands of
41
mature mice, Lasnitzki observed that hyperplasia resulted
during exposure to 2 |ag/ml and 4 |-Lg/ml for 10 days; this
process continued after withdrawal and was accompanied by
squamous metaplasia. Mitosis was increased 4 days after
exposure to MC.
Mitosis and DNA synthesis in mouse prostate gland
tissue were compared by Lasnitzki and Pelc. They con-
cluded that mitosis was stimulated before DNA synthesis.
2.3 Effects on Plants
No information on the effects of organic carcinogens
on plants has been found in the literature.
2.4 Effects on Materials
No information has been found indicating that materials
of commercial or industrial importance are affected by organic
carcinogens.
2.5 Environmental Air Standards
Recommended limits of 200 |ag/m3 for an 8-hour workday
have been adopted by the American Conference of Governmental
o CQ
Industrial Hygienists for coal tar pitch volatiles (benzene
fractions containing anthracene, BaP, phenanthrene, acridine,
chrysene, pyrene, etc.).
-------
41
3. SOURCES
3.1 Natural Occurrence
Organic carcinogens are primarily unwanted by-products
of imperfect combustion. However, a few sources of organic
carcinogens might be defined as naturally occurring.
Bituminous coal contains BaP, benz(a)anthracene, and
•p /- A
other PAH. However, studies in England reveal a lower
incidence of lung cancer among coal miners than in the popu-
lation at large. ' Consequently, although carcinogenic
agents are present in raw coal, they have no apparent bio-
264
logical effect in that form.
Asbestos miners, in comparison to coal miners, have
94
a greater potential for developing malignancy. Two of the
three types of asbestos used industrially contain appreciable
quantities of natural oils. These oils, which adhere to
asbestos particles, contain BaP- The quantities (1 to
5 |ag/100 g asbestos) are small enough that their presence
94
may play no more than a minor carcinogenic role.
Another potential naturally derived source of airborne
262
carcinogens has been reported by Troll, namely, various
molds in the environment that possibly produce toxic compounds,
some of which may be carcinogenic.
-------
42
3.2 Production Sources
Prior to the introduction of gasoline and diesel
engines, PAH were emitted primarily from the burning of coal
and other solid fuels used for home and industrial heating
as well as for the production of industrial products and
power. However, in recent times the use of gasoline and diesel
engine fuels has resulted in a new major source of PAH.
The U.S. Public Health Service, recognizing the need
for specific emission data, has obtained information concerning
those sources that involve burning conventional fuels and
90,91
certain commercial and municipal solid wastes. ' The
sources of heat generation that were tested ranged in size
from residential heaters to heavy industrial power plant
boilers and employed the following firing methods: (1) pulver-
ized coal burners, chain grate stokers, spreader stokers,
underfeed stokers, and hand-stoked coal burners; (2) steam-atom-
ized, centrifugal-atomized, and vaporized-oil burners; and (3)
premix gas burners. The incineration sources tested ranged
from small commercial incinerators to large municipal inciner-
ators. Open-burning sources and several industrial processes
were also tested. From these studies, in conjunction with the
annual consumption and production figures, sufficient emission
data were collected to reveal the probable major sources of
-------
43
carcinogenic agents as indicated in Table 6, in the Appendix.
In interpreting the significance of this information, it
should be remembered that the calculation of total emissions
involved a considerable amount of estimation, as well as a
number of assumptions, with respect to both emission rates
and annual consumption or production figures. Also, the
aggregate emissions from a number of small sources not con-
sidered in this study, although probably small, cannot be
91
estimated.
As shown in Table 6 in the Appendix, the sources were
separated into four major categories: heat generation, refuse
burning, industrial processes, and motor vehicle operation.
This study revealed that each category contributes to the
atmospheric loading of BaP. Generally, the importance of a
particular category or source has been evaluated in terms of
the United States as a whole, but the importance of a partic-
ular source, relative to concentrations found in the atmosphere,
undoubtedly varies considerably with locality; e.g., although
no coal is burned in Los Angeles County, the city of Los Angeles
has areas of exceptionally high traffic density- Other factors
may also influence the concentrations of BaP and other poly-
nuclear hydrocarbons found in the atmosphere, such as decom-
position or reaction with smog constituents in the atmosphere.
-------
44
The results and implications from these studies have
been summarized by Hangebrauck et. al.. 1 as follows:
(1) Although each process surveyed undoubtedly contrib-
utes to the amount of BaP in the atmosphere, the most important
source of BaP is the inefficient combustion of coal, typified
by residential and small industrial coal-fired furnaces.
(2 ) The efficient combustion of coal in modern
industrial-process heating boilers and power plants and the
combustion of fuel oil and natural gas do not appear to be
significant contributors.
(3) In refuse burning, as in coal burning, efficiency
of combustion governs the emission of polynuclear compounds.
Inefficient combustion in small incinerators as well as open
burning results in considerable formation of BaP and other
polynuclear hydrocarbons, whereas efficient combustion in
municipal incinerators results in very little BaP formation.
(4) Results from direct and indirect sampling of
industrial sources, although not conclusive, indicate that
the following processes are not major sources of BaP: an
asphalt air-blowing process (pyrene emissions were high),
an asphalt hot-road-mix plant, a carbon-black manufacturing
area, a steel and coke manufacturing area, and a chemical
industry complex.
-------
45
(5) Direct samples of the effluent from the catalyst
regenerators of petroleum catalytic cracking units indicate
that Houdriflow and Thermofor (air lift) units can be signifi-
cant industrial sources of BaP and other polynuclear hydro-
carbons. Emission of these compounds can be, and frequently
is, reduced to negligible amounts through the use of CO-waste
heat boilers on individual "cat-cracker" catalyst regener-
ators. Thermofor (bucket lift) and Fluid units incorporate
catalyst regenerator designs that result in minor emissions
only. Considerable additional testing would be necessary
to statistically assure the evaluation of contributions
from catalyst regenerators, as for all of the sources tested.
(6) Consideration of the emission rates determined for
gasoline-powered automobiles and trucks, as well as of their
annual fuel usage, indicates that motor vehicles are a major
contributor of BaP in the atmosphere. This is confirmed by
39
Colucci and Bregeman, who report automotive BaP contri-
butions of 5 to 42 percent, based on ratios of lead to BaP
in exhaust and in the atmosphere. Evidence indicates that
old high-mileage vehicles and those with poorly adjusted
engines have the highest emission rates.
(7) Limited data indicate higher emission rates for
gasoline-powered trucks than for automobiles. Diesel-powered
-------
46
251
trucks may also have higher rates; however, diesel fuel
usage by trucks and buses accounts for only about 4 percent
of the total petroleum consumption for motor vehicles. The
overall contribution from all trucks and buses, both gasoline
and diesel-powered, possibly exceeds that from automobiles,
although the total fuel usage for this category is about half
that for automobiles.
See Section 3.3 for further discussion of PAH emissions
from automotive exhaust.
A number of studies which deal with PAH emission from
specific types of industries have been reported and are dis-
cussed briefly in the following paragraphs.
The PAH composition of air polluted by coal-tar pitch
211
has been studied by Sawicki et al. Coal-tar pitch pollution
is characterized by much higher ratios of pyrene to BaP, BaP
to benzo(g,h,i)perylene, and BaP to coronene, when compared
213
with other types of pollution. Sawicki also suggested
that these ratios are also probably characteristic of the two
types of pollution produced from the combustion of gasoline
and coal.
Specific studies have been made of BaP levels in an
254
iron and steel works, of PAH concentrations both in a gas
139 96
works retort house and in stack gases from pulp mills,
-------
47
292
and of BaP in coke oven wastes as well as in the vicinity
of a coal briquet factory. The atmospheric emissions
produced by oil burners has been reported to be 0.04 to
2 31
0.10 pounds of BaP per million pounds of oil. Methods
for sampling from various coal-fired steam-generating instal-
54
lations are also reported. A Russian study states that the
asphalt, concrete, tar roofing, and rubber industries are
45
carcinogenic foci with regard to pollution of city air.
No detailed studies of the distribution of pollu-
91 270
tants by prevailing winds have been reported. ' However,
it can be inferred that after distribution by the winds, the
carcinogens fall back to earth. If the carcinogens fall into
water, they may spread for considerable distances. Il'nitskii
and Varshavskaya in a review article have discussed PAH
determinations in ground water, streams, and harbors. PAH
were also detected in the aquatic life of these waters.
3.3 Product Sources
As discussed earlier.- exhaust from internal combustion
engines has resulted in a significant new source of PAH. The
emission rate per gallon of fuel and the annual emission of
BaP are presented in Table 6 in the Appendix.
Carcinogenic emissions from automotive sources can
be divided into at least two major categories: PAH, and the
-------
48
photochemical pollutants that are precursors of alkylating
agents. For PAH emissions, Kotin and Falk have reviewed
the literature pertaining to analysis of exhaust prior to
approximately 1963. The primary conclusions are that a
broad spectrum of PAH, including several carcinogens, can be
detected in exhaust products; and the yield of PAH decreases
with the efficiency of the engine used. In regard to the
104
latter conclusion, Hoffmann and Wynder have quantified
the BaP yield on the basis of engine mileage and found that
the BaP concentration varied from 5 |J.g/minute sample early
in engine life (8,000-12,000 miles) to 27 |ag/minute late in
engine life (29,000-33,000 miles). When the diesel exhaust
from an engine operating inefficiently under maximum load at
varying rpm's was analyzed, BaP yield was found to vary from
876 i-ig/minute to 1,687 ng/minute.
More recent studies on automotive exhaust products
have been conducted in the following areas: (1) production
of PAH by cars and trucks, (2) contribution of automotive PAH
to total PAH, (3) carcinogenicity of automotive exhaust, and
(4) formation of carcinogens other than PAH. Each of these
areas is discussed below in greater detail.
The reports dealing with the production
of PAH have fairly uniform conclusions. For example:
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49
(1) Automobiles with properly adjusted carburetors
generated and discharged less carbon monoxide and less BaP
into the atmosphere.
(2) The highest concentrations of BaP and carbon
monoxide were discharged in exhaust gases from automobiles
operated at low rpm, usually at the time of starting or
159
accelerating. Aldehyde emissions showed a similar pattern.
(3) The concentrations of BaP and carbon monoxide
pollution in atmospheric air can be reduced substantially by
controlling carburetor operation at all times, particularly
when starting and moving into line with the traffic; keeping
the carburetor clean and well adjusted; and reducing the
number of stops and starts at crossings and light signals to
a minimum. This can be accomplished with proper regulation of
traffic, as for example through better synchronized signal
lights and use of overhead and underground auto routes which
would allow automobiles to travel without making many stops.
Several studies relating the contribution of auto-
motive PAH to total PAH have been reported. A recent test
39
was conducted in Detroit, Mich. The study showed that the
mean contributions by automobiles to the total amount of BaP
in the air at three sites were- 18 percent for freeway.-
5 percent for downtown, and 42 percent for suburbs (in winter)
-------
50
These results are based on the dilution factor of exhaust
concentration over atmospheric concentration found for lead.
Based on the carbon monoxide dilution factor, the results
were: 35 percent for freeway, 10 percent for downtown, and
32 percent for suburban areas (in winter). An earlier study
from the same laboratory had estimated the PAH concentrations
21
to be lower.
The carcinogenicity of automotive exhaust has also
been studied. ' ' Wynder and Hoffmann reviewed the
2 86
pertinent literature prior to about 1962. There is general
agreement that exhaust tars are carcinogenic to experimental
animals, the major portion of the activity is due to PAH, and
the emissions are dependent upon the type of fuel used.
Another source of PAH is cigarette smoking. (The
relation of cigarette smoking to cancer is briefly discussed
in Section 2.)
Photochemically reactive compounds, which may be pre-
cursors of carcinogenic alkylating agents, are emitted as
by-products of incomplete combustion. The major sources of
these pollutants are automobile operation and use of natural
fuels.
The foregoing discussion outlines the major product
sources of carcinogens. There are other reports in the
-------
51
O —j £-
literature of possible sources of carcinogens. The Weisburgers
have reported that nitrosamines are included in 20 patented
products. Rubber tire dust is also given as a source of BaP.
There are also several reports concerning petroleum products
229 265 290
which contain carcinogens. ' '
3.4 Environmental Air Concentrations
In a survey of 103 urban and 28 nonurban areas of the
United States in the late 1950's, the U.S. Public Health
Service found that concentrations of PAH were present in the
213 217
atmosphere of all locations studied. ' Selected values
for the winter months (January through March) of 1959 are
119 217
given in Table 7 in the Appendix. ' These values show
the striking contrast in urban and rural BaP concentrations.
109 127 214
Additional recent studies in the United States ' '
29 30 150 223 272
and other countries ' ' ' ' have shown a similar
wide distribution and urban-rural differences. The concen-
tration of nine various other PAH in particulate matter of
selected cities was measured in 1958-1959 (see Table 8, in
213
the Appendix). The data indicate that BaP is only a small
percentage of the PAH, ranging from approximately 5 to 20
percent of the nine PAH measured.
There is also a wide seasonal variation in BaP con-
centrations in urban areas. Data showing this variation are
-------
52
given in Table 9 in the Appendix.39'90'103 These data
are
relatively outdated, yet they have been presented in recent
1 88
surveys by Hoffmann and Wynder and by Sawicki . Sim-
ilar surveys have been conducted in Australia, Belgium,
Canada,150 Czechoslovakia,76'230 Denmark,29 Germany, 100' 131
Great Britain,30'249'271'273 Hungary,185 Italy,18'161'266'
the Netherlands, Norway, Poland, South Africa,
146 and Sweden.73
Concentrations of BaP in 106 urban and nonurban areas
of the United States were measured by the National Air Sampling
4
Network in 1966. These data are tabulated in Table 10 in the
Appendix. The maximum station average value reported was
0.0112 |~ig/m3 for urban areas and 0.00145 ug/m3 for nonurban
areas; the arithmetic average value was 0.00279 ug/m3 and
0.00035 |J.g/m3, respectively.
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53
4. ABATEMENT
Emissions of PAH are generally associated with con-
ditions of incomplete combustion of carbonaceous materials.
Emission sources include motor vehicles, refuse burners, and
domestic and industrial facilities that burn coal, oil, or
gas. Methods presently being studied to control these
emissions include more efficient techniques for combustion
of fuels, collection or trapping of emissions (particularly
in the form of particulates), and use of combustion treat-
ment techniques for the emissions (such as direct-flame or
catalytic afterburners). In a 1967 study of polynuclear
91
hydrocarbon sources, Hangebrauck et_ .al_. made the following
comments on abatement for particular sources:
(1) Heat generation. Replacement of inefficient
coal-fired furnaces would greatly reduce emissions attrib-
utable to heat generation.
(2) Motor vehicles. Control systems applied to
automobiles and trucks for the purpose of reducing emissions
of total gaseous hydrocarbons should reduce emissions of BaP
and other polynuclear hydrocarbons, but no data are available
to prove that this is possible.
(3) Refuse burning. The burning of all refuse
(especially that with a high ratio of hydrogen to carbon) in
-------
54
modern municipal incinerators or disposal by noncombustion
methods would almost eliminate emissions attributable to
refuse burning.
91
Hangebrauck et al. found that emissions of poly-
nuclear hydrocarbons from the catalytic regenerators of
petroleum catalytic cracking units can be reduced to negli-
gible amounts through the use of carbon monoxide-waste heater
boilers. The data (see Table 6 in the Appendix) indicate
well over 99 percent reduction upon passage through the
carbon monoxide boiler.
In addition, fuels containing BaP and other carcino-
gens may be thermally pretreated before use to remove or
292
destroy these carcinogens. Yanysheva .et_ _al_. reported
success in removing BaP from fuel bricks by heat treatment.
Heating the fuel bricks in an electric oven at 60 C for
2 hours and 15 minutes reduced the BaP content from an
average of 0.07 percent BaP to 0.0000017 percent.
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55
5. ECONOMICS
No information has been found on the economic costs
of organic carcinogen air pollution. However, in 1967,
169
Ridker estimated the cost to the economy of diseases
associated with air pollution, including cancer of the respir-
atory tract. Although this study does not indicate the rela-
tive contribution of organic carcinogens as compared with
inorganic carcinogens, occupational hazards, smoking, etc.,
the study does demonstrate that cancer as a result of air
pollution may result in significant economic losses. According
to Ridker, the costs of a disease may be classified ac-
cording to four categories: (1) those due to premature death,
(2) those associated with morbidity (i.e., burial), (3) those
incurred for treatment, and (4) those incurred for prevention
or avoidance.
For the first category, Ridker reports a model that
estimates the loss of output due to premature death. While
Ridker elaborates considerably on the assumptions (using 1958
as a base year), the mathematical model is as follows:
oo p * p^ • p^ • V
a. a a n
V = £ 123
(1 + r)n ~ a
-------
56
where
Va is the present value of the future earnings of
an individual at age a;
P is the probability that an individual at age a
1 will live to age n;
P& is the probability that an individual at age a,
2. living to age n, will be in the labor force at
age n;
Pa is the probability that an individual at age a,
3 living and in the labor force at age n, will be
employed at age n;
Y is the earnings at age n; and
r is the rate of interest.
The costs of premature death were calculated from
statistical data for the labor force.
Burial costs have been similarly calculated. If
death is postponed/ society delays using resources for burial.
The gain thereby obtained is the difference between the present
cost of burial and the present value of the expected cost of
future burial. This can be calculated from the following
formula:
c
"-a
1 - S
Pn
a
-------
57
where
Ca is the present value of the net expected gain
from delaying burial at age a;
C is the cost of burial;
n
Pa is the probability that an individual at age a
will die at age n; and
r is the discount rate.
The costs of treatment and absenteeism were esti-
mated from specific data derived from a variety of sources.
As indicated in Table 2, cancer of the respiratory
system is the most costly of these diseases.
No information has been found on the economic costs
of the abatement of organic carcinogen air pollution.
-------
TABLE 2
RESOURCE COSTS PER YEAR OF DISEASES ASSOCIATED WITH AIR POLLUTION
(Millions of Dollars)a
169
Costs Associated with Selected Diseases
Type of
Cost
Cancer
of the
Respiratory Chronic Acute Common
System Bronchitis Bronchitis Cold Pneumonia Emphysema Asthma
Premature
death
Premature
burial
Treatment
Absenteeism
518
15
35
112
18
0.7
89
52
6
0.2
b
b
b
200
131
329
13
73
75
62
b
b
59
138
60
Total
680
159.7
6.2
331
490
64
259
Using a discount rate of 5 percent.
DNot applicable.
00
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59
6. METHODS OF ANALYSIS
Several publications have compared methods and pro-
vided an overview of the role of analytical chemistry in
carcinogenesis studies.177'187'215'262'276 The methods of
analysis generally consist of the following sequence of
steps: (1) sampling, (2) extraction, (3) separation, and
(4) analysis.
6.1 Sampling Methods
Organic carcinogens are usually associated with par-
ticulates and thus are collected as "particulates." Sampling
is often accomplished with a "high-volume" air sampler, the
particulates (with which the relevant compounds are associated)
being collected on a glass-fiber filter. Collection into a
liquid (cyclohexane) absorbent has also been employed. The
collection process may continue for many days, in order to
obtain sufficient quantities of material. A technique which
has proved satisfactory for collecting BaP from high-temperature
gas streams is the use of a series of water bubblers and con-
densate traps immersed in an ice-water bath, followed by a
238
high-efficiency filter.
6.2 Extraction Methods
The organic carcinogens are generally removed from
the particulates by solid-liquid extraction, although liquid-
-------
60
liquid extraction, sublimation, and distillation (for coal-tar
1 p-y
mixtures) have also been used.
Solid-Liquid Extraction. Particulates are commonly
extracted from the atmosphere with either benzene or cyclo-
187
hexane. Other solvents used include chloroform, acetone,
isooctane, methanol, and dimethylformamide, as well as benzene
mixtures of aliphatic hydrocarbons or methanol. The solvent-
particulate mixtures can be stirred at a certain temperature
or a Soxhlet extraction can be used.
Recent studies have been concerned with the efficiency
233
of extraction. Stanley et al. showed that in the analysis
of equal weights of air particulates enriched with BaP,
benz(c)acridine, and 7H-benz(de)anthracen-7-one, the percent-
ages of these compounds extracted ranged from 50 to 100, 15
to 100, and 40 to 80, respectively. The solvents were cyclo-
hexane, benzene, methylene chloride, and acetone.
CO
In another study Dubois et al. stated that benzene
was of questionable value as an extracting agent for the
initial preparation of an air sample. The larger amounts of
material extracted by benzene, as compared with cyclohexane,
lead to analytical interferences in the subsequent analyses.
2
Aigina and Mints found somewhat similar results in that the
extinction of BaP fluorescence called for a controlled content
-------
61
of 1, 12-benzoperylene as an internal standard.
6.3 Separation
Techniques used for separating the different organic
carcinogens include column chrotnatography, thin-layer chroma-
187
tography, and gas chromatography.
6.3.1 Column Chromatography
Column chromatography is the common method for sepa-
ration of a complex mixture of PAH.
Column chromatography techniques are sufficiently
advanced that predictions can be made with regard to adsorba-
187
bility of hydrocarbons on alumina. Structural studies
have shown that adsorbability is greater for:
(1) A compound with more rings; e.g., chrysene is
adsorbed more strongly with phenanthrene;
(2) A compound with more double bonds; e.g.,
benz(a)anthracene is adsorbed more strongly than pyrene;
(3) An acene (a linearly condensed arene) than for
an isomeric phene (an angularly condensed arene); e.g.,
naphthacene is adsorbed more strongly than benz(a)anthracene;
(4) Fluorenic hydrocarbons than for pericondensed
hydrocarbons with the same number of rings and double bonds;
e.g., HH-benzo(b)fluorene is adsorbed more strongly than
pyrene;
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62
(5) The most nearly coplanar compound of a group;
e.g., the decreasing order of adsorbability, 2-phenylanthra-
cene>l-phenylanthracene>9-phenylanthracene/ follows the in-
creasing angle of twist in these molecules;
(6) A hydrocarbon substituted with an increasing
number of sterically unhindered methyl or alkylene groups
than for the hydrocarbon itself; e.g., 9-methylanthracene is
adsorbed more strongly than anthracene; and
(7) The most extensively conjugated isomer; e.g.,
l-(2-naphthyl)cyclopentene is adsorbed more strongly than
3-(2-naphthyl)cyclopentene.
It is postulated that adsorption on alumina involves
pi-type complexation where the active sites on the alumina
are relatively broad electron-attracting areas to which the
electron-donating hydrocarbon substrate is held monomolecularly
and preferentially in a planar configuration parallel to the
surface, if such arrangement is sterically possible.
In general, the columns and techniques used are com-
promises between better separations and analytical speed. ' '
195 200 209 210
' ' ' For example, the cyclohexane elution of an air
sample can take two weeks and require 500 to 600 fractions
totaling 5,000 ml. To speed up the process it is customary
to add increasing amounts of ethyl ether. This speeds the
-------
63
removal of solutes from the column but at the expense of
59
resolution. The chromatographic separation can also be
speeded by the use of alumina deactivated by the addition
of 1.6 to 1.8 percent water. If the alumina were not deacti-
vated to this extent, the PAH would come off the column too
59
slowly-
O "1 Q
Hydrocarbons are eluted in the following order:
aliphatics, olefins, benzene derivatives, naphthalene deriva-
tives, dibenzofuran fraction, anthracene fraction, pyrene
fraction, benzofluorene fraction, chrysene fraction, benzo-
pyrene fraction, benzoperylene fraction, and coronene frac-
tion. For example, with alumina containing 13.7 percent
water,- the pyrene fraction was found in the beginning of the
3 percent ether eluent; the chrysene fraction followed in the
last part of the 3 percent ether eluent; the benzopyrene
fraction appeared in the beginning of the 6 percent ether
eluent, followed by the benzoperylene fraction in the start
of the 9 percent ether eluent, and the coronene fraction
shortly afterward in the same 9 percent ether eluent. Al-
though the relative location of the fractions was always the
same, unknown variables sometimes caused the fractions to
elute sooner or later than expected. The fractions were
fairly well separated, although test tubes containing the
-------
64
tail end of one fraction usually contained small amounts of
the next fraction. Most fractions were found in three to six
tubes. However, the benzoperylene and coronene fractions were
each spread over 6 to 10 tubes.
Column chromatography studies have also been reported
195 200
by Sawicki et al.f ' in which the separation of polynuclear
aza-heterocyclic hydrocarbons and polynuclear aromatic amines
was considered. The procedures are essentially the same as
for PAH. However, the alumina does cause some decomposition
of the amines; e.g., 9-aminoanthracene is recovered in 70 per-
cent yield as anthraquinone, while 2-aminoanthracene is in
only 26 percent yield.
6.3.2 Thin-Layer Chromatography
187
In his 1964 review Sawicki noted that although
thin-layer chromatography had been applied only to a small
extent in the separation of PAH, it would find increased
use; since that time there have been a sizable number of
13—15 143
thin-layer chromatography (TLC) studies reported. ' '
1 Q1 9 OR 0 "\A. 977
±yj.-tva,tj
-------
65
of developing solvents have been evaluated for use in TLC.
Several authors ' ' ' state that the complete analysis
procedure generally consists of extraction followed by separ-
ation using either TLC or paper chromatography, and then spot
193
location by fluorescence or color development. One reagent
used for color development is 7,7,8,8-tetracyanoquinodimethan,
which reacts with polynuclear compounds to form colored pi
complexes.
277
White and Howard give R values (the ratio of the
migration distance of the substance to the migration distance
of the solvent front) for 29 PAH on cellulose and cellulose
acetate adsorbents. Such values, however, are quite specific
for a given adsorbent and developing solvent. The R values
c
alone are inadequate for characterizing polynuclear com-
pounds.207
The efficiency of separation and recovery by TLC has
also been studied.13'202'206'234 Typical results are those
O (~\O O r*\£.
reported by Sawicki et al. ' in which recoveries of
65 percent for 9-acridanone and 85 percent for BaP were ob-
tained. Assays for these same compounds were also run using
fluorometric procedures after TLC separation. It was possible
O (~\ O
to detect 9-acridanone in concentrations of .0004 p.g/m3 . For
O (~\£i
BaP the identification limit ranged between zero and .04 |Jg.
-------
66
Previously Sawicki and Johnson192 had reported the following
identification limits: anthracene, 0.01 ug; phenanthrene,
1.0 ug; fluoranthrene, 0.01 ug; chrysene, 0.01 g.g; pyrene,
0.001 |jg; and BaP, 0.001 u.g.
The separation and characterization of polynuclear
aza-heterocyclic hydrocarbons and polynuclear aromatic amines
have also been reported.14'15'204'208 The identification
limits are in the same range as for PAH; examples are: car-
bazole, 0.02 ug; llH-benzo(a )carbazole, 0.02 |ag; 1-azacarbazole,
0.2 ug; and 1,2-dinaphthylamine, 0.1 ug.
6.3.3 Gas Chromatoqraphy
A limited number of gas chromatography studies have
been conducted.31"33'53'67'279 Although the procedures are
still in the process of being worked out, the method promises
to be relatively rapid, provided the various chromatographic
peaks have been identified. As an example of the capabilities
of the method, the following amounts of PAH in soot have been
^ o
reported: acenaphthylene, 4,700 Ug/g soot; phenanthrene,
5,500 Ug/g soot; fluoranthrene, 5,200 ug/g soot; chrysene,
6,300 ug/g soot; and BaP, 2,900 Ug/g soot.
6.3.4 Other Techniques
Electrophoresis has also been considered a possible
82 212
means of separating pollutants after collection. '
-------
67
212
Reports show that separations of polynuclear phenols and
of macromolecular material82 are feasible; however, no
quantitative information is given.
6.4 Analysis
Analyses of the eluate fractions from chromatography
are conducted chiefly via ultraviolet absorption measurements
187
or fluorescence measurements. Presently, the National Air
O fc.
Pollution Control Administration analyzes airborne partic-
ulates for BaP by a fluorescence method (a modification of
210
the one described by Sawicki et al. ) using thin-layer
chromatography for separation (see References 234 and 206).
The following discussion briefly reviews the various
analytical procedures that are applicable to the study of
airborne carcinogens.
6.4.1 Spectral Methods
Methods based on ultraviolet-visible absorption spectra
and fluorescence spectra play a prominent role in the identi-
fication and determination of polynuclear hydrocarbons. The
advantages of absorption spectra are that the wavelength
maximum of a compound is unaffected by the presence of other
compounds, quenching effects are absent, and the absorption
curves of many PAH are available in the literature. The main
disadvantage, compared to fluorescence, is the lower sensi-
tivity- For many fluorescent compounds, the excitation and
-------
68
emission spectra are 10 to 10,000 times more sensitive than
their absorption spectrum. The disadvantages of fluorescence
spectra are the poorer reproducibility, the fewer available
quantitative spectra, and quenching that can drastically affect
the sensitivity and shape of the spectral curve.187
Several recent articles have dealt with spectral
methods. Of these, one was a preliminary communication con-
cerned with the detection of impurities in commercial poly-
259
cyclic hydrocarbon samples. The remaining articles are
118
concerned with the methods of ultraviolet-visible spectra '
129,156,189,216 and fluorescence spectra.194'205 The results
of these studies are summarized in Table 3.
6.4.2 Other Methods
o ~i a.
In one study, Sawicki et al. also investigated the
application of the piperonal test to the benzene-soluble
fraction of airborne particulates. Piperonal reacts with
aromatic compounds to give a colored product which obeys
Beer's law. The correlation coefficients between BaP concen-
trations and the piperonal test were 0.95 for 174 urban samples
and 0.89 for 25 nonurban samples.
Two papers deal with thermochromic tests for deter-
mining the amounts of polynuclear compounds containing the
190 . ,. . 203
fluorenic methylene group and polycyclic p-quinones.
-------
69
TABLE 3
SUMMARY OF RECENT INVESTIGATIONS IN SPECTRAL METHODS
Method
Compound(s) Procedure
Normal Range
of
Sensitivity
Refer-
ence
Ultraviolet Benzo (a )pyrene Column 1 to 6 |ag/ml 156
chroma tography
Ultraviolet DiLenz (a, j] - Hexane 0.5 to 5 l-ig/ml 118
anthracene extraction
Ultraviolet Benzo (a )pyrene Benzene 0 to 45 [ig/1,000 216
extraction /m3 air
Ultraviolet Benzo(a)pyrene Hexane 10~2 ug/ml 129
extraction
Ultraviolet Benzo (a)pyrene Modified 0.003 p, moles/ml 189
Pyrene Piperonal 0.01 p. moles/ml
Perylene tests 0.001 (J. moles/ml
Fluorescence Benzo (a)pyrene Acetophenone- 2.5 x 10~° M 205
Perylene trif luoroacetic 10~" M
acid
Fluorescence Perylene Pentane 0.3 M-g/ral 194
Anthanthrene extraction 0.3 ug/ml
Benzo(a)pyrene 0.4 |J.g/ml
-------
70
In both cases borohydrides were used at reflux temperatures
for color development. Identification limits ranged from
3 to 40 [ag. A somewhat similar study was reported in which
4-azobenzenediazonium fluoroborate was used to develop color
in the determination of aniline, naphthylamine, and anthramine
derivatives. The identification limits were in the range of
2 to 20 |jg.
A direct method of determining BaP has been devised
using its characteristic quasi-line emission spectrum at
160
liquid nitrogen temperatures. The method has been used
to determine BaP in the air of submarine crew quarters, typ-
ically about 1 ppm.
Bioassay techniques have been reported in which the
response of a microorganism is correlated with carcinogenic
activity.63'65'66'282 These techniques are based on the
phenomenon known as photodynamic action where a combination of
light energy and chemical sensitizer (in this case PAH) causes
the immobilization and death of Paramecium caudatum. Defini-
tive assay for BaP can be performed in the 0.001 to 100 ug/ml
region.
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7. SUMMARY AND CONCLUSIONS
Epidemiological studies indicate a possible relation-
ship between air pollution and lung cancer mortality in the
United States and other countries. While the role of cigarette
smoking is clearly better defined, the role of air pollution
and possibly of organic carcinogens is less certain but is
still believed to be present. The existence of urban-rural
differentials and migrant-native differentials speak of a
possible contribution of air pollution to total lung cancer
mortality.
Animal experiments indicate that under certain con-
ditions many of the organic carcinogens found in ambient air
can produce tumors. In most of the experiments, the compounds
were painted on the skin. However, these investigations have
shown that synergistic and antagonistic effects are important.
Thus, some compounds, such as phenols, have been found capable
of promoting or reinforcing the action of organic carcinogens.
Inhalation experiments indicate that benzo(a)pyrene (BaP)
adsorbed on inert particulates (iron oxide) causes a higher
incidence of lung tumors in hamsters than just BaP alone.
Moreover, these tumors were of the same types observed in
humans. In contrast, many noncarcinogenic polynuclear aro-
matic hydrocarbons (PAH) can reduce the potency of organic
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72
carcinogens, at times to such an extent that no effect is
found.
No information has been found in the literature con-
cerning the effects of airborne organic carcinogens on plants
or materials.
The atmospheric carcinogens fall into three principal
categories, namely, PAH, polynuclear heterocyclics and
oxygenated compounds, and alkylating agents. There are very
little data available on cocarcinogens and anticarcinogens
that may be present in the air.
The major sources of PAH are heat generation, refuse
burning, industrial processes, and motor vehicles. Of these,
heat generation accounts for more than 85 percent of the PAH
emitted, with the other three sources each accounting for
about 5 percent of the total. Similar figures for other
organic carcinogens have not yet been estimated.
Sources of aza-heterocyclics and polynuclear carbonyl
compounds have not been well established. Combustion prod-
ucts such as coal tar are likely sources.
Only limited data are available on the concentra-
tion of organic carcinogens in the ambient air. In 1966,
the concentrations of BaP in 106 urban and nonurban areas
were measured0 The average value was 0.00279 |_ig/m3 for
urban areas and 0.00035 |_ig/m3 for nonurban areas. Other
data indicate that BaP constitutes only a small'percentage
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73
(as low as 5 percent) of the total PAH present in the
atmosphere.
Control methods for organic carcinogens are being
studied in connection with hydrocarbon and particulate con-
trol programs.
The costs of premature death attributable to air
pollution and the associated costs of treatment and burial
have been estimated. These costs for cancer of the respira-
tory system were estimated to be $680 million per year on
the basis of 1958 data. However, no information has been
found on the economic costs of organic carcinogen air pollu-
tion or on the costs of its abatement0
Determination of organic carcinogens (mainly PAH)
commonly involves separation of the different PAH by chroma-
tographic techniques, followed by analysis by ultraviolet-
visible absorption spectra, fluorescence spectra, or phos-
phorescence spectra.
Based on the material presented in this report,
further studies are suggested in the following areas:
(1) Expansion of current efforts to determine the
atmospheric concentrations of organic carcinogens. Specific
airborne carcinogenic material as well as the composition of
hydrocarbon mixtures should be identified. Particle size
and geographical distribution should also be determined.
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74
(2) Expansion of animal research to resolve the role
of airborne carcinogens, cocarcinogens, and anticarcinogens
in pulmonary human cancer.
(3) Determine the significance of the role of
organic carcinogens in the so-called "urban factor."
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75
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-------
96
272. Waller, R.E., and B.T. Commins, Studies of the Smoke and
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-------
97
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-------
APPENDIX
-------
APPENDIX
99
HC = CH
I
H-
I
C32H66
C10H22
(plus other hydrocarbons)
(Cg - C2 unit)
Benzo(a)pyrene
FIGURE 2
Benzo(a)pyrene Pyrosynthesis (as Suggested by Badger)
103
-------
APPENDIX
100
u
FIGURE 3
Pathways for the Pyrosynthesis of Benzo(a)pyrene
103
-------
Chrysene
Benzo(e)pyrene
(1, 2-benzopyrene)
Benz(e) acephenanthrylene
(3, 4-benzofluoranthene)
Dibenzo(e, I)pyrene
(1, 2, 3, 4-dibenzopyrene)
Benz(a)anthracene
(1, 2-benzanthracene)
Benzo(a)pyrene
(3, 4-benzopyrene)
Benzo(j)fluoranthene
(10, 11-benzofluoranthene)
Dibenzo(a, h)pyrene
(3, 4, 8, 9-dibenzopyrene)
lndeno(1, 2, 3-cd)pyrene
(o-phenylenepyrene)
Dibenzo(a, i)pyrene
(3, 4, 9, 10-dibenzopyrene)
ti
td
§
H
X
FIGURE 4
Carcinogenic Polynuclear Aromatic Hydrocarbons
Identified in Urban Air103
o
-------
APPENDIX
102
N
Dibenz(a, h)acridine
(1, 2, 5, 6-dibenzacridine)
N
Dibenzla, i)acridine
(1, 2, 7, 8-dibenzacridine)
O
I
Anthanthrone
Phenalene-9-one
O
in
Xanthene-9-one
O
IV"
7H-benz(de)!anthracen-7-one
FIGURE 5
Aza-Heterocyclics and Polynuclear Carbonyl
Compounds Identified in Urban Air
103
-------
N02 + hv * NO + 0
0 H
O—0 HJD
CH2 — CH2 + O3 ^ ^ 2\ CH2
HO — CH,— O— O — CH,— OH
CH,
R - C = CH2 + 0-
r CHs -i
R —
-
C
R-(
C — CH2
\J
^>
CH3
I
1
R — C+— OO"
\^
t
+ HCHO
'H3 ^^ CH3
: — CH, R-C = o 4
V/
O
H20
FIGURE 6
Reaction Pattern Showing the Products of Decomposition of
Unsaturated Hydrocarbons. Identification Accomplished by
Infrared Spectroscopy and Gas Chromatography.-'-°°
o
co
-------
TABLE 4
TUMOR INDUCTION IN MICE FOLLOWING CUTANEOUS ADMINISTRATION OF
ORGANIC EXTRACTS OF PARTICULATE ATMOSPHERIC POLLUTANTS64
Particulates Extract
Administration
Latent
Period % Tumor Yield
(months) Local Distant
Comments
Filtration and Benzene-
precipitation ether
Large capacity Benzene
collectors
Filtration and Dichloro-
sedimentation ethane
Large volume
collectors
Ventilation
filters
Oxidation
products of
aliphatics
Filtration of
city smoke
Benzene
Benzene
and 2
fractions
Benzene
Benzene
Subcutaneous x 1 12 6
(-50,000 ug)
Subcutaneous x 1 16 8
(-50,000 ug)
Painting 3 x wkly 6 38
(10% benzene sol.)
Painting 3 x wkly 15 42
(acetone sol.)
Painting 3 x wkly ? 45
(1% benzene sol.)
Painting 3 x wkly 14 20
(acetone sol.)
Painting 6 x only 18 20
(1% benzene sol.)
Multiple
Adenomas
Multiple
Adenomas
16
Particulates from 5
urban sites
Similar tumor yields
from samples of 5
urban sites
Particulates from 3
urban sites
Particulates from
Los Angeles
Particulates from
Liverpool, England
Aromatic-free aero-
sol collected in
Shepherd traps
Particulates from
Newcastle, England
continued)
-------
APPENDIX
TABLE 4 (Continued)
TUMOR INDUCTION IN MICE FOLLOWING CUTANEOUS ADMINISTRATION OF
ORGANIC EXTRACTS OF PARTICULATE ATMOSPHERIC POLLUTANTS
Particulates
Extract
Administration
Latent
Period
(months)
% Tumor Yield
Local
Distant
Comments
Composite
NASN
samples
Composite
NASN, camp,
samples
Benzene Subcutaneous x 24 9-26
and 3 (organic ~130,000 |ag )
fractions (aromatic ~13,000-
33,000 ug) (oxygenated
-12,000 |ag) (aliphatic
-24,000 |ag); Painting
2 x wkly (aliphatic
and oxygenated)
Benzene Subcutaneous x 3 3-12
to neonates (15,000-
25,000 uq)
2-10
Hepatomas,
8-83; Lympho-
mas, 1-17;
Multiple
adenomas, 13-
75
Different tumor
yields from samples
of 8 urban sites.
In general, low
tumor yields
obtained
Different tumor
yields from samples
of 6 urban sites.
Results suggest role
of several carcino-
gens
o
Ln
-------
TABLE 5
TUMOR INCIDENCE FOLLOWING INJECTION OF ORGANIC ATMOSPHERIC POLLUTANTS TO NEONATAL MICE
64
Groups
Series
Un injected controls
Solvent controls
Chicago '63 (10024)
Cincinnati ' 63
(10025)
Los Angeles '63
(10026)
Dose (|_ig).
of Organic
Pollutants
0
0
25 , 000
25,000
25,000
No.
Neonates
Iniected
90
100
117
123
77
Sex
M
F
M
F
M
F
M
F
M
F
No.
at
Weaninq
36
37
47
42
42
37
32
31
27
22
No.
at
RiskD
30
36
44
39
22
37
16
27
11
21
o/
/o
Pulmonary ,
Solitary
13
3
11
8
27
19
25
11
36
5
Tumor Incidence3
Adenomas,
Multiple
0
0
0
0
50
19
63
74
27
10
Hepa-
tomas
7
0
2
0
14
0
31
4
9
0
Lympho-
- ma
0
0
0
0
5
8
6
15
18
5
aTests terminated at each 50 weeks.
•'-'Excluding deaths <50 weeks from unrelated causes, notably obstructive renal failure in
males, also losses due to cannibalism or autolysis.
-------
TABLE 6
ESTIMATED ANNUAL BENZO(A)PYRENE (BAP) EMISSIONS FOR THE UNITED STATES
91
Source
Estimated BaP
Emission
Rate
Estimated Annual
Consumption
or Production
Estimated Annual
BaP Emission
(tons)
Heat generation
Coal
Residential
( i ) hand- stoked
( ii ) underfeed
Commercial
Industrial
Electric generation
Oil
Gas
Total
Refuse burning
Incineration
Municipal
Commercial
Open burning
Municipal refuse
Grass, leaves
Auto components
Total
(^g/106 Btu)
1,400,000
44,000
5,000
2,700
90
200
100
( jag/ton )
5,300
310,000
310,000
310,000
26,000,000
(1015 Btu)
0.26
0.20
0.51
1.95
6.19
6.79
10.57
(106 tons)
18
14
14
14
0.20
400
9.7
2.8
5.8
0.6
1.5
1.2
421.6
0.1
4.8
4.8
4.8
5.7
20.2
(continued)
-------
TABLE 6 (Continued)
ESTIMATED ANNUAL BENZO(A)PYRENE (BAP) EMISSIONS FOR THE UNITED STATES
Source
Estimated BaP
Emission
Rate
Estimated Annual
Consumption
or Production
Estimated Annual
BaP Emission
(tons)
Industries
Petroleum catalytic
Cracking (catalyst regeneration)
(10° bl)
(i)
(ii)
HCCC
(i)
(ii)
TCCa
(i)
(ii)
cc
no Co boiler
with CO boiler
no CO boiler
with CO boiler
(air lift)
no CO boiler
with CO boiler
(bucket lift)
(i) no CO boiler
(ii) with CO boiler
Asphalt road mix
Asphalt air blowing
Carbon-black manufacturing
Steel & Coke manufacturing
Chemical complex
240
14
218,000
45
( iag/bl )
90,000
<45
<31
50 |ag/ton
<1 0,000 ug/ton
790
790
23.3
43.3
(106 bl)
131
59
119
0
187,000 tons
4,400 tons
0.21
0.012
5.6
0.0024
13.0
<0.0029
0.0041
0
0.000010
<0. 000048
Atmospheric samples indicate that BaP Emissions
from these processes are not
extremely high
Total
18.8
(continued)
o
OD
-------
TABLE 6 (Continued)
ESTIMATED ANNUAL BENZO(A)PYRENE (BAP) EMISSIONS FOR THE UNITED STATES
Source
Motor vehicles
Gasoline
Automobiles
Trucks
Diesel
Total
Total (all sources tested)
Estimated BaP
Emission
Rate
170
>460
690
Estimated Annual
Consumption
or Production
(1010 gal)
4.61
2.01
0.257
Estimated Annual
BaP Emission
(tons)
8.6
2.0
>20.6
481
d
FCC: fluid catalytic cracker.
CO boiler: carbon monoxide waste heat boiler,
"HCC: Houdriflow catalytic cracker.
TCC : Thermo for catalytic cracker.
O
-------
APPENDIX
110
TABLE 7
BENZO(A)PYRENE CONCENTRATIONS IN URBAN
SAMPLING SITES FOR JANUARY THROUGH MARCH 1959
J-iy '
State
Alabama
Alaska
Arizona
Arkansas
California
Colorado
Connecticut
Delaware
District of
Columbia
Florida
Georgia
Illinois
Indiana
Iowa
Kansas
Kentucky
Louisiana
Maine
Maryland
Massachusetts
Michigan
City
Montgomery
Anchorage
Phoenix
Little Rock
Berkeley
Glendale
San Bernardino
San Diego
San Jose
Denver
Hartford
New Britain
New Haven
Wilmington
Washington
Miami
Orlando
Tampa
Savannah
Chicago
Rockford
East Chicagoa
Indianapolis
Hammond
South Bend
Des Moines
Topeka
Wichita
Louisville
Shreveport
Portland
Baltimore
Boston
Lowell
New Bedford
Worcester
Dearborn
Flint
Grand Rapids
ng BaP/g
of Particulate
340
64
15
20
41
5.3
13
20
7.2
51
68
50
53
55
71
28
110
140
49
74
63
34
120
280
91
160
40
19
70
6.4
180
64
45
40
81
66
110
140
91
ug BaP of
Benzen,e Soluble
Fraction
2,000
540
160
230
260
38
140
150
91
290
730
450
580
650
59
250
810
1,200
480
950
660
710
1,100
2,600
200
1,600
510
310
860
150
2,100
650
730
410
1,000
700
960
1,400
1,400
lag BaP/
m3 air
.024
.0038
.0050
.0015
.0029
.0008
.0023
.0021
.00056
.0069
.0065
.0055
.0053
.010
.0093
.0019
.011
.015
.0043
.015
.0073
.0111
.026
.039
.016
.023
.0031
.0023
.016
.00065
.021
.014
.0096
.0031
.0044
.014
.0090
.015
.015
-------
APPENDIX
111
TABLE 7 (Continued)
BENZO(A)PYRENE CONCENTRATIONS IN URBAN
SAMPLING SITES FOR JANUARY THROUGH MARCH 1959
State
Minnesota
Mississippi
Missouri
Montana
Nebraska
Nevada
New Hampshire
New Jersey
New Mexico
North Carolina
North Dakota
Ohio
Oklahoma
Oregon
Pennsylvania
Rhode Island
South Carolina
South Dakota
Tennessee
Texas
City
Duluth13
Minneapolis
Jackson
Kansas City
St. Louis
Helena
Omaha
Las Vegas
Manchester
Bayonne
Jersey City
Newark
Paterson
Albuquerque
Charlotte
Raleigh
Bismarck
Cleveland
Columbus
Dayton
Hamilton
Toledo
Youngs town
Tulsa
Portland
Allen town
Altoonaa
Erie
Johnstown
Pittsburgh
Scran ton
York
Providence
Charleston
Columbia3
Sioux Falls
Chattanooga
Knoxville
Beaumont
Dallas
Galveston
Houston
San Antonio
of Particulate
110
73
24
46
200
2.4
33
16
53
33
33
46
51
15
290
180
5.8
110
70
78
83
100
190
13
96
26
280
70
58
16
33
31
24
68
120
31
120
210
13
6.1
3.4
12
5.8
ug BaP/g of
Benzene Soluble
Fraction
1,500
1,600
230
540
1,800
51
460
160
600
410
440
500
610
460
2,100
1,300
130
1,200
930
760
600
1,200
2,000
180
730
440
1,400
1,000
660
200
360
510
240
530
750
480
1,000
1,900
200
160
50
210
110
|jg BaP/
m3 air
.012
.014
.0012
.0065
.054
.00011
.0035
.0014
.0060
.0055
.0060
.0045
.0063
.0063
.039
.014
.00044
.024
.0095
.0079
.014
.011
.028
.0010
.0080
.0034
.061
.0095
.016
.0051
.0061
.0056
.0029
.0056
.024
.0040
.031
.024
.00082
.0014
.00016
.0016
.00086
(continued)
-------
APPENDIX
112
TABLE 7 (Continued)
BENZO(A)PYRENE CONCENTRATIONS IN URBAN
SAMPLING SITES FOR JANUARY THROUGH MARCH 1959
State
City
of
lag BaP/g
Particulate
ug BaP/g of
Benzene Soluble |j.g Bap/
Fraction
rrr
air
Utah
Vermont
Virginia
Washington
West Virginia
Wisconsin
Wyoming
Salt Lake City
Burlington
Norfolk
Richmond
Roanoke
Seattle
Charleston
Wheeling
Madison
Milwaukee
Cheyenne
5.4
28
59
410
160
81
40
140
80
60
36
54
39
580
1,900
1,100
790
900
1,600
830
730
340
.00052
.0010
.0084
.045
.018
.0090
.014
.021
.0049
.0085
.0012
aln respect to the cities with benzo(a)pyrene levels greater
than 11 |ag/l,000 m3 of air, five cities had a concentration of particu-
lates in the air 1.5 to 2 times higher than in the corresponding
January to March period in 1958.
The concentration of particulates in the air for this city in
January to March 1959 was half that found in the corresponding period
of 1958.
-------
TABLE 8
POLYNUCLEAR HYDROCARBON CONTENT OF PARTICULATE MATTER FOR SELECTED CITIES
213
City
Winter 1959
( |~ig/g benzene soluble
fraction)
Atlanta
Birmingham
Detroit
Los Angeles
Nashville
New Orleans
San Francisco
Seattle
Sioux Falls
South Bend
Wheeling
Youngs town
Summer 1958
( |-ig/g benzene soluble
fraction)
Atlanta
Birmingham
Cincinnati
Detroit
Los Angeles
Nashville
New Orleans
Philadelphia
San Francisco
Month
Feb.
Feb.
Feb.
Feb.
Jan.
Feb.
Jan.
Jan. -Mar .
Jan .-Mar.
Jan . -Mar .
Jan . -Mar .
Jan . -Mar .
July
July
July
July
July
July
July
July
July
Compound*
BqhiP*
830
1090
2100
510
880
760
590
1200
1000
1500
1100
1600
510
950
600
1500
200
440
530
960
720
BaP
690
1500
2000
150
1300
430
180
790
480
2000
1600
2000
160
730
390
950
43
180
230
480
69
BeP
440
610
1500
230
710
670
230
—
—
1700
—
—
150
670
400
840
54
150
360
350
150
BkF
560
800
1300
160
790
410
130
710
330
1300
990
1300
130
520
350
770
39
130
210
350
67
P
560
1000
1600
170
1400
240
150
590
480
3900
1700
2400
73
240
170
440
23
75
39
310
25
Cor
400
210
410
330
240
280
380
1300
440
480
360
240
250
270
280
290
190
160
290
410
450
Per
100
330
390
44
230
84
27
210
99
370
200
530
40
240
93
270
29
27
45
110
12
Anth
48
130
130
4.5
92
11
8.1
91
27
190
110
240
20
29
6.5
61
2.4
7.7
12
17
6.1
Total
3628
5670
9430
1599
5642
2885
1695
4891
2856
11440
6060
8310
1333
3649
2290
5121
580.4
1170
1716
2987
1499
*BghiP = Benzolg, h, ilperylene; BaP = Benzo(a)pyrene; BeP = Benzo(e)pyrene; BkF
Benzo(k)fluoranthene; P = Pyrene; Cor = Coronene; Per = Perylene; Anth = Anthanthrene
H
U)
-------
APPENDIX
114
TABLE 9
SEASONAL EFFECT ON THE BENZO(A)PYRENE CONCENTRATIONS
OF VARIOUS URBAN ATMOSPHERES
Concentrations
(Ug/m3 of air)
Location
Atlanta, Ga.
Birmingham, Ala.
Cincinnati, Ohio
Detroit, Mich.
Location I
Location II
Location III
Los Angeles, Calif.
Nashville, Tenn.
New Orleans, La.
New York, N.Y.
Herald Square
Columbus Circle
Philadelphia, Pa.
San Francisco, Calif.
South Charleston, W. Va.
Year
1958
1960
1958
1960
1958
1960
1958
1961
1961
1963
1958
1958
1958
1960
1963-64
1964
1958
1958
1960
S ummer
(low)
0.0016
0.0009
0.006
0.003
0.002
0.0012
0.0034
0.0072
0.0036
0.0002
0.0004
0.0014
0.0020
0.0006
0.0005
0.0007
0.0025
0.0003
0.0006
Winter
(high)
0.015
0.014
0.074
0.062
0.026
0.018
0.031
0.017
0.0137
0.0018
0.013
0.055
0.006
0.007
0.0094
0.0026
0.019
0.0075
0.012
-------
APPENDIX
115
TABLE 10
CONCENTRATIONS OF BENZO (A)PYRENE IN THE AMBIENT AIR, 19664
(iag/m3 )
Location
1st
Quar.
2nd
Quar.
3rd
Quar.
4th
Quar
Yearly
Avq
Alabama
Birmingham
Gadsden
Mobile
Alaska
Anchorage
Arizona
Grand Canyon
,0163
.00297
.00239
,00392
,0163
,00297
,00239
,00392
,00536
,00176
,00671
,00063
,036
,00626
,01430
,00063
.01849
.00349
.00645
.00228
National Park*
Paradise Valley
Phoenix
Tucson
Arkansas
Little Rock
Montgomery County*
Texarkana
West Memphis
California
Bur bank
Humboldt County*
Los Angeles
Oakland
Pasadena
San Diego
San Francisco
Colorado
Denver
Montezuma County*
Connecticut
Hartford
New Haven
Delaware
Kent County*
Newark
Wilmington
.00028
.00000
.00135
.0005
.00072
.00036
.00027
.0009
.00211
.00026
.0024
.00306
.00171
.00117
.00108
.00104
.00006
.00248
.00324
.00074
.00072
.00162
.00028
.00000
.00135
.0005
.00072
.00036
.00027
.0009
.00211
.00026
.0024
.00306
.00171
.00117
.00108
.00104
.00006
.00248
.00324
.00074
.00072
.00162
.00036
.00104
.00266
.00041
.00126
.00012
.00086
.00054
.0005
.00032
.00086
.00122
.0005
.00041
.00095
.00225
.00010
.00135
.00239
.00046
.00135
.00158
.00022
.00023
.00140
.00095
.00198
.00042
.00207
.00513
.00056
.00257
.00356
.00339
.0041
.00122
.00486
.00006
.0027
.00504
.00038
.00108
.00378
.00029
.00032
.00169
.00059
.00117
.00032
.0011
.00246
.00035
.00206
.00273
.00183
.00171
.00108
.00230
.00007
.00225
.00348
.00058
.00097
.00215
-------
APPENDIX
116
TABLE 10 (Continued)
CONCENTRATIONS OF BENZO(A)PYRENE IN THE AMBIENT AIR, 1966
Location
District of Columbia
Washington
Georgia
Atlanta
Hawaii
Honolulu
Idaho
Boise
Butte County*
Illinois
Chicago
Indiana
East Chicago
Hammond
Indianapolis
Monroe State Forest*
Muncie
New Albany
Parke County*
South Bend
Terre Haute
Iowa
Davenport
Delaware County*
Des Moines
Dubuque
Kansas
Kansas City
Wichita
Kentucky
Ashland
Covington
Louisville
1st
Quar.
.00090
.00113
.00009
.00266
.00010
.00266
.00752
.00572
.011
.00044
.00207
.00293
.00134
.00117
.00689
.00509
.00074
.00279
.00509
.00108
.00068
.0122
.00288
.00257
2nd
Quar.
.00090
.00113
.00009
.00266
.00010
.00266
.00752
.00572
.011
.00044
.00207
.00293
.00134
.00117
.00689
.00509
.00074
.00279
.00509
.00108
.00068
.0122
.00288
.00257
3rd
Quar.
.00068
.00144
.00023
.00167
.00010
.00306
.00707
.00248
.00707
.00048
.00257
.00099
.00026
.00284
.00806
.00158
.00216
.00171
.00149
.00032
.00657
.00225
.00167
4th
Quar.
.00693
.00185
.00023
.00680
.00495
.005
.00149
.0124
.00050
.00275
.0147
.00054
.00378
.00095
.00018
.00243
.00225
.00108
.00144
.0109
.00432
.00324
Yearly
Avq
.00235
.00139
.00016
.00345
.00333
.00678
.00385
.01037
.00047
.00237
.00539
.00087
.00224
.00318
.00254
.00354
.00118
.00078
.01047
.00308
.00251
(continued)
-------
APPENDIX
117
TABLE 10 (Continued)
CONCENTRATIONS OF BENZO(A)PYRENE IN THE AMBIENT AIR, 1966
(ug/m3 )
Location
Louisiana
New Orleans
Maine
Acadia National Park*
Portland
Maryland
Baltimore
Calvert County*
Michigan
Detroit
Minnesota
Duluth
Minneapolis
Moorhead
St. Paul
Mississippi
Jackson
Jackson County*
Missouri
Kansas City
St. Louis
Shannon County*
Montana
Helena
Glacier National
Park*
Nebraska
Omaha
Thomas County*
Nevada
Las Vegas
White Pine County*
1st
Quar.
.00203
.00012
.00180
.0023
.001
.00459
.00149
.00108
.00045
.00176
.00086
.0002
.00234
.00698
.00008
.00234
.00024
.00392
.00012
.00099
.00004
2nd
Quar.
.00203
.00012
.00180
.0023
.001
.00459
.00149
.00108
.00045
.00176
.00086
.0002
.00234
.00698
.00008
.00234
.00024
.00392
.00012
.00099
.00004
3rd
Quar.
.00158
.0004
.00171
.00171
.00024
.0027
.00396
.00099
.00063
.00126
.00099
.00006
.00122
.00167
.00004
.00018
.00046
.00131
.00008
.00041
.00002
4th
Quar.
.00347
.00008
.00177
.00473
.00022
.00702
.00198
.00342
.0014
.00243
.00239
.00014
.00108
.00563
.00008
.00077
.00028
.00167
.00026
.00266
.00008
Yearly
Avq
.00228
.00018
.00177
.00276
.00062
.00473
.00223
.00164
.00073
.00180
.00128
.00015
.00175
.00532
.00007
.00141
.00031
.00271
.00015
.00126
.00005
(continued)
-------
APPENDIX
118
TABLE 10 (Continued)
CONCENTRATIONS OF BENZO(A)PYRENE IN THE AMBIENT AIR, 1966
Location
New Hampshire
Concord
Coos County*
New Jersey
Camden
Glassboro
Jersey City
Marlton
Newark
Perth Amboy
Trenton
New Mexico
Albuquerque
Rio Arriba County*
New York
New York City
Cape Vincent*
North Carolina
Charlotte
Cape Hatteras*
Ohio
Akron
Cincinnati
Cleveland
Columbus
Dayton
Toledo
Young stown
Oklahoma
Cherokee County*
Oklahoma City
Tulsa
Oregon
Curry County*
Portland
1st
Quar.
.00054
.00024
.0027
.00081
.00509
.0014
.00225
.00189
.00216
.0023
.00018
.00491
.0002
.00509
.00016
.00468
.00432
.00356
.00405
.00275
.00221
.00567
.00024
.00176
.00086
.0001
.00293
2nd
Quar.
.00054
.00024
.0027
.00081
.00509
.0014
.00225
.00189
.00216
.0023
.00018
.00491
.0002
.00509
.00016
.00468
.00432
.00356
.00405
.00275
.00221
.00567
.00024
.00176
.00086
.0001
.00293
3rd
Quar.
.00041
.00016
.00207
.00018
.0023
.00117
.00054
.00189
.00063
.00036
.0001
.00158
.00032
.00077
.00018
.00153
.00113
.00207
.00162
.00203
.0009
.00599
.00008
.00108
.00041
.0001
.00104
4th
Quar.
.00077
.00028
.00441
.00113
.00419
.00095
.0032
.00266
.00369
.00311
.00028
.005
.00016
.0119
.00038
.00545
.00441
.00338
.00194
.00329
.00185
.0118
.00022
.00122
.00068
.00012
.00626
Yearly
Avq
.00057
.00023
.00297
.00073
.00417
.00123
.00206
.00208
.00216
.00202
.00019
.0041
.00022
.00571
.00022
.00409
.00355
.00314
.00292
.00271
.00179
.00728
.0002
.00146
.0007
.00011
.00329
-------
APPENDIX
119
TABLE 10 (Continued)
CONCENTRATIONS OP BENZO (A)PYRENE IN THE AMBIENT AIR, 1966
(ug/m3)
Location
P enn sy 1 van i a
Clarion County*
Lancaster
Philadelphia
Pittsburgh
Reading
Warm in star
Westchester
Puerto Rico
Bayamon
Guayanilla
Ponce
San Juan
Rhode Island
Providence
Washington County*
South Carolina
Columbia
Greenville
Rich land County*
South Dakota
Black Hills Forest*
Sioux Falls
Tennessee
Chattanooga
Memphis
Nashville
Texas
Dallas
Houston
Matagora County*
Pasadena
San Antonio
1st
Quar.
.0017
.00176
.0041
.00608
.00207
.0009
.0009
.0005
.00027
.0005
.00149
.00284
.00028
.00239
.005
.00212
.00012
.00095
.00621
.00081
.00545
.00113
.00099
.00028
.00041
2nd
Quar.
.0017
.00176
.0041
.00608
.00207
.0009
.0009
.0005
.00027
.0005
.00149
.00284
.00028
.00239
.005
.00212
.00012
.00095
.00621
.00081
.00545
.00113
.00099
.00028
.00041
3rd
Quar.
.00066
.00032
.00158
.00527
.00063
.00018
.00014
.00018
.0005
.00041
.00144
.00022
.00045
.00081
.00018
.00016
.00054
.00167
.00077
.00117
.00131
.00063
.00026
.00032
4th
Quar.
.00172
.00522
.00536
.00203
.00437
.00176
.00074
.0014
.00095
.0009
.00743
.00032
. 009 18
.00046
.00018
.00077
.0193
.00423
.00981
.00189
.00095
. 00044
.00122
.00104
Yearly
Avq
.00145
.00227
.00379
.00487
.00229
.00094
.00047
.00053
.00061
.00107
.00364
.00028
.005
.00122
.00015
.0008
.00835
.00166
.00541
.00137
.00089
.00032
.00055
-------
APPENDIX
120
TABLE 10 (Continued)
CONCENTRATIONS OF BENZO (A) PYRENE IN THE AMBIENT AIR, 1966
Location
Utah
Ogden
Salt Lake City
Vermont
Burlington
Orange County*
Virginia
Danville
Norfolk
Shenandoah Park*
Wisconsin
Door County*
Milwaukee
Wyoming
Cheyenne
Yellowstone Park*
1st
Quar .
.00014
.00018
.00113
.00136
.0014
.00216
.00132
.00028
.00617
.00054
.00006
2nd
Quar.
.00014
.00018
.00113
.00136
.0014
.00216
.00132
.00028
.00617
.00054
.00006
3rd
Quar.
.00041
.00005
.00050
.00036
.00086
.00041
.00032
.00131
.00037
.00002
4th
Quar.
.00149
.00455
.00041
.00068
.00905
.00662
.00068
.00275
.00063
.00008
Yearly
Avq
.00055
.00124
.00079
.00094
.00318
.00284
.00091
.00410
.00052
.00006
*Indicates nonurban areas.
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