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OCR for page 395
Table A-2 (continued)
Structural Formula Name
12 1
11 ~ 2
Chrysene
9 ~ 3
7
2 1
Benzo[a]pyrene
~,'Z ~ 3
5
sW6
Benz[e]pyrene
~Perylene
9 ~ 7
8 ~ S
1^ ~ .- I ~ 3
Molecular
Weight
228.0939 0/+
252.0939 ++
252.0939 0/+
252.0939 0
Benzo[j~fluoranthene 252.0939 ++
A-11
Carcinogenic
Activity
~... ..
OCR for page 396
Table A-2 (continued)
Structural Formula Name
2
1'~s
9 8 7
2
44
18
1l ~ 13
Molecular Carcinogenic
Weight Activity
Benz~e]acephenan-
thrylene
(Benzotbifluoranthene
252.0939 ++
Benzo~k~fluoranthene 252.0939
2
7H-Dibenzotc,g~car- 267.1048
2
5
7H-Dibenzota,g]car- 267.1048 +
bazole
11 2
4 -b Dlbenzo[a,i]car- 267.1048
A-12
A;
++
+
- . . .
OCR for page 397
Table A-2 (continued)
Structural Formula
3
~2 ~ 7
12 2
3 4
12 2
34
8 7 6
2
12 ~ 4
IO ~ 8
9
12 1
1l ~ 2
Molecular Carcinogenic
___ Weight Activity
Benzo[~]naphtho[l, 2- f ] - 279 a 1048 +
qulno. . 1ne
Dibenz[a,j]acridine 279. 1048 +
Dibenz[c,hiacridine 279.1048 +
13
Dibenz[a,h]acridine 279.1048 +
Benzo[ghi]perylene 276.0939 +
A-13
OCR for page 398
Table A-2 ~ continued ~
Structural Formula Name
. _
1l 12
9~3 _..
9~3
1~3
12
0~8
2
I `~3
'I
12
ION ,7
9 8
3
2~4
1~6
7
2 19
11 R0
Molecular
We ight
u~uenzo [clef ,mno I-276.0939
chrysene
~ Anthanthrene ~
Indeno ~ 1, 2, 3-cd ~ pyrene276.0939 +
Dibenz [a ,h ~ anthracene
~ 278.1096 +
Benzotcichrysene278.1096 +
Benzo ~ g ~ chrysene
A-14
Carc inogenic
Activity
lo
278.1096 +
OCR for page 399
Table A-2 (continued)
Molecular Carcinogenic
Structural Formula Name Weight Activity
2
3
8
10[ ~ 3
8 7 6
2
21 ~ 4
- 2
I,> ~ 14
12 2
~o~l.
8 7 6
Picene 278.1096 0
14 1
13 ~ 2 Benzotb]chrysene
278.1096 0
Benzotb~triphenylene 278.1096
(Dibenz~a,c~anthracene)
+
Pentaphene 278.1096 0
(Dibenzo[b,h]phen
anthrene)
Dibenz[a,j]anthracene 278.1096 +
A-15
OCR for page 400
Table A-2 (continued)
S tructural Formula Name
|2 ~
t0~3
Molecular
We ight
-
Coronene 300.0939
2
14 ~Benzo[rat]pentaphene 302.1096 ++
11 ~ (Dibenzo[a,i]pyrene)
9 8 7
13 14 1
12~2 Dibenzo [b, de f ] chrysene 302. 1096
IO ~ (Dibenzo[a,h~pyrene) ~
9 ~ 5
1346
12~8
11 10 9
11~2
a
NA = not available.
Care inogenic
Ac t ivity
0/+
++
Dibenzo[def,p]chrysene 302.1096 ++
( Dibenzo [ a, 1 ] pyrene ~
Naphtho[ 1,2 ,3,4-def]- 302. 1096 ++
chryeene
( Dibenzo [ a, e Jpyrene
A-16
a. .. . .
OCR for page 401
TABLE A-3
Nitroarenes Detected in Diesel-Exhaust Particulate Extracts:
Molecular Formulas and Molecular Weights
Struc
ture Molecular Molecular
No. Name Formula Weight
Mononitroarenes:
1 Nitroindene C9H7NO2 161.16
2 Nitroacenaphthylene C12H7NO2 197.19
3 N~troacenaphthene C12HgNO2 199.21
4 N~trobiphenyl C12H9NO2 199.21
5 Nitrofluorene C13H9NO2 211.22
6 Nitromethylacenaphthylene C13H9NO2 21L.22
7 Nitromethylacenap~thene C13HllNO2 213.24
8 Nitromethylbiphenyl C13HllNO2 213.24
9 Nitroanthracene C14HgNO2 223.23
10 Nitrophenanthrene C14H9NO2 223.23
11 Nitromethylflourene C14HllNO2 225.25
12 Nitromethylanthracene ClsHLlNO2 237.26
13 Nitromethylphenanthrene C15HLlNO2 237.26
14 Nitrotrimethylnap~thylene C13H13NO2 215.25
15 N~trofluoranthene C16HgNO2 247.25
16 N~tropyrene C16HgNO2 247.25
17 Nitro(C2-alkyl~anthracene C16H13NO2 251.29
18 N,tro(C2-alkyl~phenanthrene C16H13N~2 251.29
19 N~trobenzofluorene C17HllNO2 261.28
20 Nitromethylfluoranthrene C17HllNO2 261.28
21 Nitromethylpyrene C17H12NO2 262.29
22 Nitro(C3-alkyl~anthracene C17H15NO2 265.31
23 Nitro(C3-alkyl~phenanthrene C17H15NO2 265.31
24 Nitrochrysene C18HllNO2 273.29
25 Nitrobenzanthracene C18HllNO2 273.29
26 Nitronaphthacene C18HllNO2 273.29
27 Nitrotriphenylene C18HllNO2 273.29
28 Nitromethylchrysene Cl9H13NO2 287.32
29 Nitromethylbenzanthracene Cl9H13NO2 287.32
30 Nitromethyltriphenylene ClgH13NO2 287.32
31 Nitrobenzopyrene C20HllNO2 297.31
32 N~troperylene C20HllNO2 297.31
33 N~trobenzofluoranthene C20HllNO2 297.31
Polynitroarenes:
34 Dinitromethylnaphthylene CllHgN2O4 233.20
35 Dinitrofluorene C13H8N2O4 256.22
36 Dinitromethylbiphenyl C13HloN2o4 258.23
37 Din~trophenantl~rene C14H8N2O4 268.23
38 D~-nitropyrene C16H8N2O4 292.25
39 Tr~nitropyrene C16H7N3O6 337.25
40 Trinitro(C5-alkyl)fluorene C18H17N3O6 371.35
41 Dinitro(C6-alkyl~fluorene Cl9HlgN2O4 339.37
42. Dinitro(C4-alkyl~pyrene C20H16N2O4 348.36
A-17
=. ...
OCR for page 402
Table A-3 (continued)
Struc
ture Molecular Molecular
NO.a Name Formula Weight
.
Nitro-oxyarenes:
-
43 NitronapUthaquinone CloH5NO4 203.L5
44 Nitrodihydroxynap~thalene CloH8NO4 206.18
45 Nitronaphthalic acid CloH8NO4 206.18
46 Nitrofluorenone C13H7NO3 225.20
47 Nitroanthrone C14H9NO3 239.23
48 Nitrophenanthrone C14H9NO3 239.23
49 Nitroanthraquinone C14H7NO4 253.21
50 Nitrohydroxymethyliluorene C14HllNO3 241.25
51 Nitrofluoranthone C16H~NO3 262.24
52 Nitrofluoranthenequinone C16H7NO4 277.24
53 Nitropyrenequinone C16H8NO4 278.24
54 Nitropyrone C16HgNO3 263.25
55 Nitrodimethylanthracene C17H12NO3 278.29
carboxaldehyde
56 Nitrodimethylphenanthrene C17Hl2No3 278.29
carboxaldehyde
Other nitrogen compounds:
57 - Benzocinnoline C12HgN2 180.21
58 Methylbenzocinnoline C13HloN2 194.24
59 Phenyloaphthylamine C 16H13N 219. 29
6 0 ( C2-Alkyl ) phony 1 naph thylamine C 1 SHE 7N 247 . 34
aStructure numbers refer to structures in Table A-4.
A-18
~.
OCR for page 403
TABLE A-4
Struc Lures of Nitroarenesa
H H
N02 ¢
1
N 0 2~3
AS
N02~1
9J12~1 7/ 22
o
11
No2~3
H H
~7
o
.,
No2~3
11
o
~9
N02~
27,30
No7~1 I
2,6
~ H
No2~3
5.L1
N O 2
10,1~.1l,~
it,
N02
16, 2
N 0 2
2`,2
N O2-~`J
31
-
C~5 H
~3
59,60
Hi;
A-19
.
~ H
H l ,H
_ _ 1
NORM ~ ~
a,7
o
C- OH
N02~
-
N02~ J
NO 2
15,20
No2~3
N02
32
^. ... .
OCR for page 404
NO 2~--3 NO2--~X63
9 25 29
o en.
NO,-~ ,,,:
26
· ~ _~
54
it'
NO2
NO2-~ ( C~3)3
14
Nit 3 N O -~3 N O 2-~ ~ o H )2
lo
57,58
o
~C`oH
NO2
~5
NOW
0 48
,,
N O2-Id
54
o
11
NO 2-
H
~7
o
ll
N 0 2-
~6
O ,0
N 0 2- ~N 0 2--
o
" O
C-H "
NO2- ~NO2-
55 , ~53
~6
"Numbers under structures refer to compounds listed in Table A-3.
A-20
51
hi. . .
OCR for page 405
APPENDIX B
POLYCYCLIC AROMATIC HYDROCARBONS IN THE AMBIENT ATMOSPHERE
Compound
Unsubstituted:
Biphenyl
Naphthalene
Anthracene
Phenanthrene
Benz~aJanthracene
Dibenz~ac~anthracene
Benzotc~phenanthrene
Benzota~fluorene
Benzotbifluorene
Dihydrobenzo~a,b
, and c]£1uorenes
Fluoranthene
Benzotbifluoranthene
Benzo~j~fluoranthene
Benzo~kifluoranthene
Benzotghi~fluoranthene
Pyrene
Benzota~pyrene
Benzoteipyrene
Anthanthrene (dibenzo~cdjk~pyrene)
Dibenzopyrenes (4 isomers)
Indeno(1,2,3-cd~pyrene
Chrysene
Perylene
BenzotghilperyLene
Coronene
Picene
Benzotc~phenanthrene
Benzotb~chrysene
Benzotc~tetraphene
Hexahydrochrysene
Dihydrobenzo~ciphenanthrene
Dihydrobenz~aJanthracene
Dihydrochrysene
Benzacenaphthylene
Binaphthyl (3 isomers)
Quarterphenyl
DiphenylacenapUthalene
Ambient concen
tration ? ng/m3 References
a
0.05-0.35
0.07-6.15
0.04-25
0.5-22
0.03-4.5
0.04-1.0
0.8
O. 1-1. l
0.03-0.9
0.1-41
0.1-7.4
0.2-4.4
0.14-20
O . 9-9 . l
0.1-35
0.1-75
0.1-42
0.1-6
a,b
1-12.8
0.2-39
0.1-5
0.2-46
0.~-48
a
a
a
a
a
a
a
a
b
b
b
b
B-1
6
6
6
6
6
6
6
1.6
6
6
6
6
6
6
6
6
6
4,6
6
6
6
6
6
1
ll
4
4
4
4
OCR for page 406
Compound
Alkyl-substituted:
Methylanthracene 0.22-0.66 6
1-, 2-, 3-, and 9-Methylphenan
threnes b 4
1-~1ethylpyrene 0.01-0.15 6
1-, 2-, and 4-Metoylpyrenes b 4
EthylanthraceneC a 1,4
EthylphenanthreneC 1, ~
Methylfluoranthene (5 isomers) a 1,4
Methylbenz~alanthracened a 1
Methylchrysened a 1
MethYlbenzotbkifluoranthene a 1
Methylbenzo~ae~pyrene a 1
Methylbenzopyrenes or benzo
fluoranthenes (5 isomers) b 4
4H-Cyclopenta~def~phenanthrene b 4
Methyl 4H-cyclopenta~def~phen
anthrene b 4
~ ~ ~ ,
thy ~ 4H-cyclopentaldef~phenanthrene
(5 isomers) b 4
Ethylmethyl 4H-cyclopenta~def]
phenanthrene b 4
Ethylmethyl anthracene or phenan
threne b ~ 4
Ethylpyrene or fluoranthene
(4 isomers) b 4
Ethylmethylpyrene or fluoranthene
(3 isomers) b , 4
Methylbenzotciphenanthrene b 4
Methylbenzotghi~fluoranthene b 4
Ethy~chrysene or benz~aJanthracene
(7 isomers) b 4
Methylbinaphthyl (4 isomers) b 4
Methyldibenzanthracene b 4
N-Hetero (aza):
_
Acridine 0.04 6
Hethylacridine 0.007 6
Benz~aJacridine 0.9 6
Benz~c~acridine 0.1-1.5 6
Dibenz~aj~acridine 0.04 6
Dibenz~ahiacrid ine 0 . 08-0 . 1 6
Carbazole 1.9 6
Quinol ine 0. 02-0 .6 6
Me thylquino 1 ine 0.03 6
2 , 6-D imethylquinol ine 0 .03 6
Dimethylquinolines 0. 04-0.09 6
Ethylquinol ines 0. 01-0 .02 6
03 Alkylquinolines 0.01 6
B-2
Ambient concen
tration, ng/m3 References
~...
OCR for page 407
Compound
Benzo~fJquinoline
Benzoth~quinoline
11-Indenot1,2b~quinoline
Phenanthridine
Isoquinoline
Methylisoquinolines
Dimethylisoquinolines
Ethylisoquinolines
C3 Alkylisoquinolines
Benz~f~isoquinolines
4-Azafluorene
4-Azapyrene and isomers
1-Azafluoranthene
Benzotcicinnoline
2-Methylindole
Benzota] carbazole
Benzotc] carbazole
Phenoxazine
C; Alkylquinolines
Me thylphenanthr id ine s
Methylbenzoquinolines
Me thylbenzoisoquino 1 ines
Azabenzofluorenes
Methylazapyrenes
Me-thylazafluoranthenes
Azabenz~aJanthracene
Azachrysenes
Azabenzopyrenes
Azabenzofluoranthenes
Dibenzoquinolines
Dibenzoisoq~inolines
Quinones:
9,lO-Anthraquinone
Benzotaipyrene 6,12-quinone
Benzota~pyrene 1,6-quinone
Benzo~aipyrene 3,6-quinone
Dibenzo~b,def~chrysene 7,L4-quinone
Phenaten-l-one
Benzanthrone
Perinaphthanone
Carboxylic acids:
Nap~thalene carboxylic acid
Phenanthrene carboxylic acid
Anthracene carboxylic acid
Pyrene carboxylic acid
Ambient concen-
tration, ng/m3
0.01-0.2
0.01-0.3
0.1
0.02
0.14-0.18
0.17-0.31
0.06
0.07-0.16
0.03
0.03-0.11
0.005
0.02-13
trace-3
1.0
.0
a
a
a
a
a
a
a
a
a
a
a
a
a
a
a
b
b
b
b
b
0.3-17
0.6-48
a
a
B-3
References
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
1
l
1
l
ll
5,6
6
1
.. ....
OCR for page 408
Compound
Phenols:
Hydroxyanthracene
Hydroxyphenanthrene
Hydroxypyrene
Hydroxyfluoranthene
S-Hetero:
-
Benzothiazole
Dibenzothiophene
Methyldibenzothiophenes (3 isomers)
Ethyldibenzothiophene
Benzo~defidibenzothiophene
Naphthobenzothiophenes (3 isomers)
Methylnaphthobenzathiophenes
(3 isomers)
Nitro derivatives:
1-Nitropyrene
3-Nitrofluoranthene
5-Nitroacenaphthene
6-Nitrobenzota~pyrene
Ambient conce~-
tration, ng/m References
a
0.014-0.02
b
b
b
b
b
b
b
b
b
l
2
4
4
4
4
4
4
7
3
aConcentration reported in micrograms per gram of part iculate matter or
micrograms per gram of benzene-soluble fraction, but not in nanograms pe
cubic meter.
Compound identified, but no concentration reported.
CEight isomers of ethylanthracene/ethylphenanthrene identified.
drive isomers of methylbenz~aJanthracene/methylchrysene identified.
B-4
me_
OCR for page 409
REFERENCES
3.
5.
Cautreels, W., and K. Van Cau~enberghe. Determination of organic
compounds in airborne particulate matter by gas chromatography-mass
spectrometry. Atmos. Environ. 10:447-457, 1976.
2. Dong, M. W., D. C. Locke, and D. Hoffmann. Characterization of aza
arenes in basic organic portion of suspended particulate matter.
Environ. Sci. Technol. 11:612-618, 1977.
lager, J. Detection and characterization of nitro derivatives of
some polycyclic aromatic hydrocarbons by fluorescence quenching
after thin-layer chromatography. Application to air pollution
analysis. J. Chromatogr. 152:575-578, 1978.
Lee, M. L., M. Novotny, and K.~. Bartle. Gas chromatography/mass
spectrometic and nuclear magnetic resonance determination of poly
nuclear aromatic hydrocarbons in airborne particulates. Anal. Chem.
48:1566-1572, 1976.
Pierce, R. C., and M. Katz. Chromatographic isolation and spectral
analysis of polycyclic quinones. Application to air pollution
analysis. Environ. Sci. Technol. 10 :45-51, 1976.
Santodonato, J., P. Howard, D. Basu, S. Lande, J. K. Selkirk, and Pe
Sheehe. Health Assessment Document for Polycyclic Organic Matter.
EPA-600/9-79-008. Research Triangle Park, N.C.: U. S. Environmental
Protection Agency, Office of Health and Environmental Assessment,
Environmental Criteria and Assessment Office, 1979. [475] pp.
(preprint)
Tokiwa, H., R. Nakagawa, and Y. Ohnishi. Mutagenic assay of aromatic
nitro compounds with Salmonella typhimurium. Mutat. Res. 91:
321-325, 1981.
B-5
OCR for page 410
OCR for page 411
APPENDIX C
HUMAN-CANCER RISK ASSESSMENT*
Malcolm C. Pike
Epidemiologic studies, animal carcinogenesis experiments, and in
vitro mutagenesis and transformation assays all provide data relevant to
the assessment of the human-cancer risk from exposure to PAHs.
The data used in this assessment are in the main taken from epidemi-
ologic studies, because they refer directly to man. It is recognized
that an alternative approach would have been the extrapolation of experi-
mental animal data to humans, but the epidemiologic approach offers two
advantages : the avoidance of interspecies extrapolation and the
derivation of results from exposures not too different from that suffered
by the general population. Epidemiologic studies often suffer from
various inadequacies, such as imprecise dose measurements and poor
measurement of confounding factors, and exposure is invariably to ~
complex mixture of PAHs and other chemicals. Extrapolation to other
complex mixtures therefore inevitably involves making assumptions, and
evidence from in vitro and in vivo experiments must be sought to provide a
rational basis for these assumptions.
At present, the two sources of human exposure to PAHs on which data
appear reliable are work around coke ovens and cigarette-smoking. The
major known human cancer associated with exposure to chemical mixtures
containing PAHs is undoubtedly lung cancer. Although cigarette-smoking is
of overwhelming importance as a cause of lung cancers ~ 40 and cigarette
smoke does contain PAHs, this appendix is concerned with cigarette-smoking
only insofar as the information derived from epidemiologic study of the
smoking population is essential in measuring the health effects that might
be expected when Germans are exposed to other PAH-containing mixtures.
The quantitative relationship between cigarette-smoking and lung
cancer has been thoroughly explored in many epidemiologic studies-° and
is well understood.8~2 However, it is still far from established that
the PAR content of cigarette smoke is responsible for the development of
lung cancer. Epidemiologic data (mainly occupational) on the relationship
*Quantitative risk assessment is ~ developing, rather than a precise,
science. The numerical estimates in this appendix are based on a series
of assumptions. The use of different assumptions or extrapolations from
animal data could lead to very d i f ferent cone lus ions. The calculated
risk values at ambient concentrations are not meant to be absolute
indicators of risk, but rather to indicate the region between the upper
bounds of risk and the lower bound of zero risk.
C-l
OCR for page 412
between exposure to other PAH-containing mixtures and lung cancer are much
less precise. The lung-cancer risks (as well as the risks of cancer at
other sites) associated with such exposures have, in fact, always been
measured in relation to lung-cancer rates in the "nonexposed," and -
cigarette-smoking has been responsible for some 90% of the lung cancers in
these "nonexposed. "9 To measure the risk, rather than the relative
risk? associated with these other exposures, it is essential to understand
the lung-cancer risk associated wi th cigare t te-smoking .
DEFINITIONS_
The incidence rate of a disease is the number of cases of the disease
_
that are diagnosed during a specified period per specified unit of
population.2 The mortality rate of a disease is the number of deaths
from the disease during a specified period per specified unit of popuLa-
tion. In epidemiologic studies, the unit of time is usually a year and
the unit of population is usually 100, 000. All incidence (and mortality)
rates quoted here for man use a period of a year, but the unit of popula-
tion is 1, unless otherwise stated. If we write the incidence rate
without qualification (e. g., I), it is assumed to refer to the standard
condition of 1 yr and 1 person. The incidence rate is often affected by
many factors, particularly age, and, if the incidence rate is for some
particular subgroup, this is stated in referring to the incidence rate,
and the symbol, I, for incidence rate is qualified in some way, e.g., I(t)
for the incidence rate for a person of age t.
For cancers associated with a substantial cure rate or a long time
between diagnosis and death, the incidence and mortality rates may be very
different. For lung cancer--the major cancer discussed in this
chapter--the distinction is not so important, because some 75t of newly
diagnosed lung-cancer patients are dead within a year and some 90t within
3 yr.
The lifetime risk of a disease is the probability of being diagnosed
as having the disease by age 70 (a "lifetime") in the absence of other
causes of death. This measure has been found particularly useful in
comparing human data and experimental-animal data and forms the basis
of current methods of extrapolating animal data to man.3 The lifetime
risk is virtually identical with the cumulative incidence rate (to age 70)
used by the International Agency for Research on Cancer.3'39
CIGARETTE-SMOKING AS A SOURCE OF PAR EXPOSURE
Much of what has been learned about the quantitative relationship
between cigarette-smoking and lung cancer over the last 30 yr may be
summarized by the statement, "The excess lung-cancer incidence of a
smoker, compared with a nonsmoker, is proportional to the number of
cigarettes smoked per day and to the duration of smoking raised to the
C-2
OCR for page 413
power 4.5~8,40 If we write the excess incidence--or single-cause
incidence 4--of a smoker aged t years who started smoking at age w years
and who smokes c cigarettes per day as Ic~t,w), that statement may be
expressed mathematically as
Ic~t,w) = scat - w)4 5, (1)
where the constant a is approximately 1.0 x 10 11 for U.K. smokers.8
For U.S. smokers the constant a must be decreased by
25-50%.12,13,19 33 The reasons for this include the use of different
tobaccos in the two countries and the mode of cigarette-smoking--in
particular, British smokers tend to smoke their cigarettes down to a
considerably shorter butt.7343 Similar reasons probably explain the
exis fence of a range.
We may express the lung-cancer risks from cigarettes in the usual
risk-assessment terms27 of "lifetime risk" by using Equation 1.
"Lifetime" is taken as 70 yr, and exposure is taken as starting at birth.
If exposure is to c cigarettes per day, Equation 1 shows that the
lung-cancer rate at age t will be
Ic~t,O' = act4 5. (2)
The lifetime risk (cumulative incidence) can be shown to be
CIC(T) = 1 - expt-ac(705 5/5.5~. - (3)
The lifetime lung-cancer risk associated with one U.K. cigarette per day
is 2,524 per 100,000, or 2.527.
The lung-cancer risks associated with smoking depend strongly on age
at which one started to smoke, i.~., on duration of exposure (see Figure
C-1. The increase in lung-cancer incidence rate of a smoker at age 60
who started to smoke at age 20 is proportional to 404 5; if he Sad
started at age 15, the extra rate would be proportional to 45 .
Starting to smoke 5 Or earlier has thus increased the extra lung-cancer
rate by 70% [~45/40) 5], or roughly 14Z for each year. To make valid
comparisons between groups of persons exposed to different concentra-
tions of PAH-containing mixtures (e.g., different occupational groups), we
must therefore know their comparative smoking habits, not only in terms of
number of cigarettes smoked per day, but also in terms of age at starting
to smoke.
For a smoker of c cigarettes/d starting at age w and stopping at age
s, the extra lung-cancer incidence rate at age t is
Ic s~t,w) = acts - w)4 5. (4)
Equation 4 states that the lung-cancer incidence rate associated with
cigarette-smokin§ y~m4~ns constant at the value it had reached when
smoking stopped. ~ ~ If a person aged 60 who has smoked 30
cigarettes/d from age 20 to 40 (30 pack-yr in total) is compared with a
C-3
OCR for page 414
person at the same age (60) who has smoked 15 cigarettes/d from age 20 to
60 (also 30 pack-yr in total), calculations using Equation 4 show that the
latter person will have more than 11 times the lung-cancer incidence rate
of the fonder. Thus, to understand quantitatively the effect of exposure
to a PAH-containing mixture, one must know not only the total cumulative
exposure, but also the time during which it is accumulated.
Hoffmann et al.17 pointed out that the major carcinogenic activity
of cigarette smoke. resides in the particulate phase (the tar) and that
there is good experimental evidence that cigarettes with lower tar yields
are less tumorigenic to both hamster larynx and mouse skin. Lower-tar
cigarettes have also been shown to be less tumorigenic to man in all
epidemiologic studies that have investigated this question. Case-control
studies have found that people who smoke filter-tip cigarettes (in effect,
lower-tar cigarettes) have lower lung-cancer incidence rates than smokers
of plain cigarettes at the same frequency,l,44~45 and Hammond et al.14
found, in the American Cancer Society (ACS) cohort study, that persons
smoking low-tar cigarettes had lower risk of lung cancer than smokers of
high-tar cigarettes (matched for numbers of cigarettes smoked per day).
Table C-1 shows the results of the ACS study: the lung-cancer
mortality ratios are clearly not decreased in men in proportion to tar
content, but they are nearly so in women. The Latter finding suggests
that the added lung-cancer risk is close to being simply proportional to
tar content and that the failure to find a proportional reduction in men
arises from the male smokers' having switched from high-tar to low-tar
cigarettes. As Hammond et al. 1 stated: "Cigarettes with reduced tar
and nicotine were not introduced until the mid 1950' s. a . . Almost all
of the male cigarette smokers and the great majority of the female
cigarette smokers in our study began smoking cigarettes tong before that
date. Therefore the subjects classified here as low [tar] cigarette
smokers were, with few exceptions, persons who smoked high ~ tar] or medium
[tar] cigarettes for many years and then switched to low [tar]
cigarettes." These results substantiate the linear dose-response
assumption of Equation 1.
EXPOSURES TO OTHER SOURCES OF PAM-CONTAINING MIXTURES
Large-scale studies of benzo[a]pyrene in the air of the United States
were conducted between 1958 and 1959 by Sawicki et al.3 The range of3
BaP concentrations in urban air was from less than 1 to around 60 ng/m
and the median was roughly 6 ng/m . In contrast BaP concentrations in
nonurban air were almost always less than 1 ng/m3, with a median of 0.4
ng/m . BaP concentrations have since decreased by 1969, the median BaP
concentration in urban air was less than 2 ng/m .2 However3 some
cities were still experiencing average annual BaP concentrations of nearly
10 ng/m3.
BaP is not a perfect indicator of either PAR in the air or its
carcinogenicity,35 and it accounts for a much Smaller fraction of the
carcinogenicity of cigarettes than of air.il,4 It should be emphasized
C-4
Representative terms from entire chapter:
lung cancer
