EPA 680 175-001
JUNE 1975
Environmental Health Effects Research Series
SYNERGISTIC EFFECT OF POLONIUM-210
AND CIGARETTE SMOKE IN RATS
NATIONAL ENVIRONMENTAL RESEARCH CENTER
OFFICE OF RESEARCH AND DEVELOPMENT
U.S. ENVIRONMENTAL PROTECTION AGENCY
LAS VEGAS, NEVADA 89114
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RESEARCH REPORTING SERIES
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5. Socioeconomic Environmental Studies
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EFFECTS RESEARCH SERIES. This series describes projects
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ful substances or conditions. This work is generally
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and other medical specialities, study areas include bio-
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EPA-680/1-75-001
June 1975
SYNERGISTIC EFFECT OF POLONIUM-210 AND
CIGARETTE SMOKE IN RATS
by
S. C. Black
E. W. Bretthauer
National Environmental Research Center
Las Vegas, Nevada
ROAP 21AMC
Program Element 1FA082
NATIONAL ENVIRONMENTAL RESEARCH CENTER
OFFICE OF RESEARCH AND DEVELOPMENT
U,S, ENVIRONMENTAL PROTECTION AGENCY
LAS VEGAS/ NEVADA 89114
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ABSTRACT
An experimental procedure was devised to test the possible syner-
gistic effect of polonium-210 and cigarette smoke in rats. Appropriate
techniques were developed to expose the rats to cigarette smoke through
mouth-breathing and to add known amounts of polonium-210 to the cig-
arette smoke.
The findings from this experiment included: 1) lung deposition of
polonium-210 was 31 ± 2%, 2) early retention of polonium was two-
phased with half-times of 4 and 84 hours, and 3) bronchitis, emphysema
and lung tumors were observed in the experimental animals. Though the
spontaneous occurrence of two lung tumors in the number of animals at
risk was highly improbable, any conclusion that this resulted from the
exposure to cigarette smoke must be highly qualified.
iii
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CONTENTS
ABSTRACT 111
List of Figures, Plates and Table v
INTRODUCTION 1
PROCEDURES 1
RESULTS 3
DISCUSSION 8
SUMMARY AND CONCLUSIONS 10
Note added in proof 10
REFERENCES 11
IV
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LIST OF FIGURES/ PLATES AND TABLE
FIGURES
Figure 1. Retention of polonium-210 in rat lung after exposure 4
to one cigarette with added polonium-210.
Figure 2. Cumulative mortality of rats in cigarette-smoking 5
experiments.
PLATES
Plate 1. Primary pulmonary neoplasm (*140) composed of tumor 6
cells that appear to be growing by expansion.
Plate 2. Small, well-circumscribed adenoma (*140) whose 6
trabeculae are covered with cuboidal to columnar
cells.
Plate 3. Adenomatous hyperplasia (x!40) surrounding a small 7
bronchus in an area of pneumonia.
TABLE
Table 1. Non-neoplastic lung pathology detected in 8
experimental rats.
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INTRODUCTION
Many hypotheses have been proposed to explain the relationship be-
tween cigarette smoking and lung cancer in humans. Because primary lung
cancer was rarely produced in experimental animals by exposure to ciga-
rette smoke alone, most postulates included one or more co-carcinogens.
Of the multitude of co-carcinogens that may be involved in the produc-
tion of primary lung cancer, ionizing radiation has been suggested as an
important possibility. Such radiation has produced lung cancer in a
variety of experimental animals as reported at a 1970 symposium.(1) The
combination of smoking and radiation exposure has also been implicated
in the elevated incidence of lung cancer among uranium miners.(2) In
the non-mining population, lung tissue receives a substantial exposure
from naturally occurring radioactive aerosols which are present in the
atmosphere.(3) It has been suggested that volatilization of
polonium-210, a naturally occurring alpha emitter which is present in
tobacco, may add sufficient radiation exposure to lung tissue to poten-
tiate the carcinogenic effect of cigarette smoking.(4)
To investigate the possibility that potentiation occurs, a two-part
study was conducted. In the first part, the polonium-210 content of
various tobaccos was measured. In addition, the amount of polonium in
mainstream smoke under standard smoking conditions and the effect of
filters on this amount were determined.(5,6) The amounts of lead-210
and radium-226 in mainstream smoke were negligible compared to the
polonium. The second part of the study, investigating the effect of
added polonium-210 on the carcinogenic activity of cigarette smoke, is
reported herein.
PROCEDURES
Before starting the animal exposure, several problems had to be
resolved. These were: 1) the animal species; 2) the treatment groups;
3) the method of adding polonium-210 to the cigarettes; 4) the exposure
dose; and 5) the method of exposure.
The animal chosen was the albino rat. There were several reasons
for this choice which outweighed the endemic murine pneumonia charac-
teristics of this species. Firstly, a colony of the Wistar strain
females had been maintained in our laboratory with little evidence of
pneumonia. Secondly, the endpoint sought was frank lung cancer rather
than precancerous changes which might be obscured by pneumonic changes.
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Thirdly, the rat is of convenient size, and much experimental data on
its response to various stresses has been accumulated. Lastly, the
incidence of primary lung cancer in rats is very low and is well docu-
mented, namely, 0.03% for all lung tumors(7) (0.015% for squamous cell)
and 0.013% for fibrous tumors in a 5-year study.(8)
The most satisfactory method of adding polonium-210 to cigarettes
was by use of sewing thread. A solution of 210Pb-Bi-Po in equilibrium
was used which contained four microcuries per milliliter in Q.5N HC1.
Mercerized cotton thread, button, extra strong, was cut to length,
thoroughly soaked in the solution, and air dried. With a needle, one
thread was placed lengthwise through the center of regular size non-
filter cigarettes. Several cigarettes from each batch were then smoked
on the smoking machine with the mainstream smoke being trapped on
filters. Analysis of the filters yielded 12.5 ± 0.8 nanocuries of
polonium-210 in the mainstream smoke of each of cigarettes to which
polonium-210 had been added.
Fifteen of the Wistar rats were each exposed to the mainstream
smoke of one cigarette containing the added polonium-210. The rats were
sacrificed immediately after exposure and the respiratory tree analyzed
for polonium-210. The results were 270 ± 30 picocuries (n=15) in the
lungs, indicating an average deposition of 31 ± 2% of the amount in-
haled. This was calculated by using the respiratory minute-volume of
the rat,(9) the exposure time, and the picocuries per cubic centimeter
of smoke; 100% deposition would have yielded 820-920 picocuries in the
lungs per exposure. Another group of sixty rats was exposed to one
polonium-210 labeled cigarette each and then serially sacrificed to
determine retention. A least-squares analysis of lung content indicated
a two-phase decrease for the polonium-210 representing biological half-
times of 4 hours and 84 hours.
The method of exposure chosen for this study was oral inhalation
because this simulates human smoking. The apparatus used and the rea-
soning used in its development are explained in a previous publica-
tion. (10) Initially, the rats were lightly anesthetized, placed in
restrainers, their nostrils closed with collodion to force mouth breath-
ing, and inserted in the smoking machine. With this procedure, several
animals died each month. The procedure was then modified to eliminate
the use of the anesthetic by gradually acclimating the rats to the
smoking routine using a stepwise progression of the treatment. The
death rate was substantially reduced, but was still higher than for non-
smoking rats.
The amount of exposure for the rat was based on calculations using
standard values. The standard cigarette smoking procedure used in our
laboratory is 8 puffs per cigarette at the rate of 1 puff per minute
with each 35-cubic centimeter puff lasting 2 seconds for a total volume
in the mainstream smoke of 280 milliliters. For one rat, then, the
exposure to 1 cigarette smoked under these conditions results in the
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inhalation of approximately 20 milliliters of smoke. This is one-
fourteenth of the amount available per cigarette. If a heavy smoker is
assumed to smoke 40 'cigarettes per day, then he will inhale 40 x 14 =
560 times as much smoke as the rat exposed to a single cigarette. Since
the fresh weight of the adult human lung is 1169 grams(11) and that of
the adult rat is approximately 2 grams, the ratio of lung weights is
580. Therefore, it was assumed that the amount of smoke per gram of
lung for a rat exposed to one cigarette daily was the same as for a
heavy smoker.
The polonium-210 exposure of the rat lung from inhaling the smoke
of a regular-size cigarette was negligible. The average mainstream
smoke concentration is 0.1 femtocuries per milliliter(5; for the
standard smoking regimen so a 20-milliliter inhalation by the rat and an
average deposition of 31% implies only 0.6 femtocuries deposited in the
lung. Using the single exposure data from the 60 rats referred to
above, a curve of lung content following multiple exposure was con-
structed. The area under the curve was integrated and the average lung
content derived assuming 31% deposition. With this lung content and
standard conversion factors, the lung exposure of rats smoking the
cigarette having added polonium-210 would average 16 millirads per day,
based on a 7-day week with 5 days of exposure. From the constructed
multiple-exposure curve, the lung content 24 hours after the final of 25
exposures (5 exposures per week) cpuld be estimated as 77 picocuries.
The lung content of 3 rats sacrificed 24 hours after the last of 28
exposures averaged 84.5 picocuries, in reasonable agreement with the
calculations.
The original plan was to conduct a modified factorial experiment
using groups of 100 rats with daily treatment of the exposed rats. The
groups would have included 1) an environmental control, 2) a collodion-
only treatment (sham smoked), 3) a polonium-210 exposure, 4) a
cigarette-smoke exposure, and 5) a cigarette-smoke plus polonium-210
exposure. Due to the exigencies of laboratory operation and limitation
of resources, the groups were limited to 60 rats per group, exposures to
5 per week, and only treatments 1), 4), and 5) were used. The exposures
continued over a two-year period with no periodic sacrifices scheduled.
Those animals in the exposure groups that died were replaced by new rats
up to the last three months of the experiment. Those that died were
examined for gross pathology and lung sections were taken for histo-
pathology. T Those remaining at the termination of exposure were main-
tained for three months, then sacrificed-for pathological examination.
RESULTS
Because animals were entered in the experimental groups to replace
those that died, a total of 381 rats was involved plus 38 used as room
controls and another 150 used to determine exposure parameters. Reten-
tion of polonium in the rat lung following exposure to a single cigarette
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containing added polonium-210 is shown in Figure 1. Analysis of the
curve suggested in Figure 1 indicates a 2-phase retention function
with 92% being retained with a biological half-time of 4 hours and 8%
with a biological half-time of 84 hours.
1000
wo
i
£
§
(t3)
(13)
(7)
24 36 48 60 72
HOURS AFTER SMOKING
84 96
108
Figure 1. Retention of polonium-210 in rat lung after exposure to one
cigarette with added polonium-210. Number of rats
shown in parentheses.
Some of the data on the two experimental groups is shown in
Figure 2 which is a long-probability plot of cumulative mortality. Also
shown in this figure are the data for the rats exposed by the original
technique. Cumulative mortality reached 50% in only 5*i weeks with the
original technique compared to 28^ weeks with the modified technique.
Also indicated on the figure are the two lung cancers detected in the
experimental groups. One cancer was a bronchogenic carcinoma detected
in an 8-months old rat which had been exposed for 15 weeks to cigarettes
having added polonium-210, and the other a pulmonary adenoma detected in
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an 18-months old rat which had been exposed for 49 weeks to normal
cigarettes. The one other cancer discovered in lung tissue was metas-
tasized from a mammary carcinoma.
100
o
&
X
10
1.0
oo°° c
0000°
o
PULMONARY ADENOMA
BRONCHOGENIC /
CANCER /
I
I
1 I
I
•-"131 RATS SMOKED CIGARETTES WITH ADDED 210Po
Ill RATS SMOKED NORMAL CIGARETTES
140 RATS-OLD SMOKING TECHNIQUE-
NORMAL CIGARETTES
•'1
0.01
Figure 2
0.1
1
10 SO 90
CUMULATIVE % MORTALITY
98 99 99.9
Cumulative mortality of rats in cigarette-smoking experiments.
The bronchogenic carcinoma is shown in Plate 1 and the adenoma in
Plate 2. In three instances a morphology was noted that was suggestive
of an early neoplastic change (Plate 3), but was considered more likely
to be part of an inflammatory response.
Many of the lung sections exhibited other phenomena such as:
1) Lymphocytic cuffing
These are peribronchiolar accumulations of lymphoid cells,
which are thought to occur normally, but proliferate in many
disease conditions. It was possible that chronic bronchiolar
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>«•."•>•. . y.
Plate 1. Primary pulmonary neoplasm (x!40) composed of
tumor cells that appear to be growing by expansion. Some
of the cells are spindled while others are plump
epithelial-like.
*•
-
Plate 2. Small, well-circumscribed adenoma (x!40) whose
trabeculae are covered with cuboidal to columnar cells.
-------
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»• «. »> 7* ^»" * • ^ "•**''• j1* ** ^ *
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.^•;- ^;
. ••
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*-. "*v"
• '• -.-
Plate 3. Adenomatous hyperplasia (x!40) surrounding a
small bronchus in an area of pneumonia. This may be an
early neoplastic change but is more likely an inflam-
matory response.
irritation caused an increased amount of lymphocytic cuffing
in these rats.
2) Focal macrophage response
These were focal accumulations of foamy macrophages,
usually found near the pleura. These are frequently seen
in normal rodent lungs and their significance is unknown.
3) A few of the lungs were pneumonic because debris and
particles of hair were seen in bronchi; most were thought
to be aspiration pneumonia. Bronchitis was seen in a few
of the lungs examined.
4) The other changes seen in the lung were very non-
specific and consisted of edema, congestion, emphysema
and atelectasis.
Other changes detected in lung tissue of the rats exposed to
cigarette smoke and in the 38 animals used as room controls are shown in
Table 1.
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Table 1. NON-NEOPLASTIC LUNG PATHOLOGY DETECTED IN EXPERIMENTAL RATS.
Number of weeks exposure until appearance of:
Early
Group Pneumonia Bronchitis Emphysema neoplastic** Atelectasis
change
Cigarettes with 13(12)*, 35(11), 9(13), 65(21) 52(26)
added polonium 36(13)
Cigarettes only 1(4), 1(4) 5(5), 7(3) 6(9), 8(5) 38(13)
13(9)
Control (10), (10) (30)
* Number in ( ) is age in months.
** These are probably an inflammatory response to pneumonia (see text).
DISCUSSION
Before discussing the effects of cigarette smoking, it is useful to
compare the retention data from this experiment with some of the pub-
lished data. The initial lung deposition of 31 ± 2% and the half-times
of 4 and 84 hours for retention as determined during this experiment
were required to estimate the lung dose. Data from the literature are
discussed below.
For a PoCl2 solution injected into the trachea of rats, Thomas and
Stannard(12^ noted a 50% decrease in lung burden in the first few hours
which changed after 10 days to an 18-day half-time. It was difficult to
decide, on the basis of the published data, whether or not an intermedi-
ate half-time existed. Initial deposition was 100% because of the tech-
nique used. Casarett(13^ used a "nose-only" exposure of rats to a
PoCl2~NaCl aerosol (0.046 pm CMD) and estimated that initial deposition
was 33%. He noted half-times for retention of 2 hours and 3 to 4 days
(72 to 96 hours). Both the initial deposition fraction and the reten-
tion half-times agree with our data. Yuile, et al.(14) also used
chloride-type aerosols, although the CMD was 0.078 ym and the duration
of exposure was 1.4 to 3.4 hours. Based on their earlier work, they
assumed the initial deposition to be 46%. Since this was a "whole-body"
exposure, the initial deposition could have been elevated by the rats
licking their fur and paws. They observed retention half-times of "a
few days" and 50 to 60 days with no estimate of half-time the first few
hours after exposure.
8
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Considering the differences in type of exposure and type of carrier
aerosol, if any, the agreement with the data from our experiment is very
good.
Statistically the appearance of lung cancers in each of the two ex-
perimental groups represents a significant incidence since the incidence
of spontaneous lung tumors in this strain of rats would suggest <0.05
tumors for either of the groups of 131 or 111 rats involved. The fact
that one of the tumors was a bronchogenic carcinoma is particularly
noteworthy.
However, any significance which may be attached to the preceding
observations must be highly qualified. The appearance of the broncho-
genic cancer in an 8-months old rat after only 15 weeks exposure leads
one to suspect that the cause of the cancer was that exposure. Admit-
tedly these animals were subject to considerable stress, such as forced
mouth breathing, and multiple inhalation insults; i.e., either from the
collodion, tobacco smoke, or alpha radiation from the polonium-210 added
to the cigarettes; but the latent period appears too short. The radia-
tion exposure, for example, represents a cumulative alpha dose of only
1.7 rads or 17 rems if the RBE is assumed to be 10. Other experimenters
have produced cancers in rodents with relatively small amounts of
radiation dose. For example, Yuile, et al.(14) observed a 3% incidence
of lung cancer in rats (1 squamous-cell carcinoma of the trachea and 3
adenomas) after a cumulative dose df 71 rads from polonium-210 inha-
lation and Grossman, et al.,(15) observed a 43% incidence of lung
cancer in hamsters with a cumulative dose of 225 rads from polonium-210
administered by intratracheal instillation. Of particular interest,
Yuile, et al.f observed adenomas only in the low- and medium-dose
groups; not in the control animals or high-dose group.
The adenoma detected in the rat exposed to normal cigarette smoke,
however, cannot be dismissed so readily. This animal had lived nearly
half its normal lifespan and had been exposed to cigarette smoke for
nearly one-third its normal lifespan. The uncertainty arises because of
the lack of an adequate control group (sham smoking), which was not
included for the reasons mentioned in the Procedures section, and the
possibility that this tumor was spontaneous even though the probability
was extremely small.
The induction of lung cancers in rodents by exposure to tobacco
smoke has generally been unsuccessful though inhalation of a constituent
of tobacco smoke (3,4-benzopyrene) attached to hematite aerosols(16)
has produced numerous cancers. The observation of lung cancers in dogs
following cigarette smoking(17) may be qualified somewhat since the dogs
smoked cigarettes through a tracheostomy. This procedure delivers the
smoke more directly to the lung than does inhalation through the mouth,
and therefore may increase the exposure to carcinogens in the smoke.
The other effects on the rat lung which could possibly result from
cigarette smoking, bronchitis and emphysema, also cannot be attributed
-------
solely to the smoke as the contribution of the collodion vapors cannot
be assessed with the data from this experiment.
Relative to the cumulative mortality curves, apparently the added
polonium exposure did not change the mortality rate. The non-parametric
Kolmogorov-Smirnov test of the hypothesis that the two groups of rats
were representative of the same population failed to reject that hy-
pothesis.
SUMMARY AND CONCLUSIONS
A method for exposing rodents to cigarette smoke in a manner which
closely simulates human smoking was developed and tested. Two tech-
nicians trained in the procedure could expose 120 rats each day to one
cigarette-smoking experience. The cumulative mortality from the stress
of the smoking procedure reached 50% in 29 weeks, but continued expo-
sures would eventually result in a cadre of animals which could survive
a year or more.
Also tested was a method for adding polonium-210 to the cigarettes
which, when smoked by Wistar-breed rats, added an alpha-radiation expo-
sure of 116 mrad/day to the lung, based on exposure to one cigarette/day
for five days/week. About 31% of the polonium-210 was deposited in the
rat lung of which 92% was eliminated with a half-time of 4 hours and the
remainder with a half-time of 84 hours.
Lung pathology which may have been produced by exposure to ciga-
rette smoke included bronchitis, emphysema, a bronchogenic carcinoma,
and an adenoma. The small number of rats exposed suggests that spon-
taneous occurrence of the neoplasms was highly improbable. The un-
certainty in this conclusion arises because adequate control groups
could not be established with the limited resources available for this
experiment.
Note added in proof;
A recent publication (Little, J. B., A. R. Kennedy and R. B.
McGandy, Science 188;737-38, May 16, 1975) tentatively supports the
carcinogenic effect of low dose of alpha radiation on the rodent lung
reported herein. Little, et al./ report that polonium-210 delivered in
15 weekly intratracheal instillations of 250 pCi, delivering a cumu-
lative lung dose of 15 rads, resulted in 9 malignant tumors for the 83
hamsters so exposed.
10
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REFERENCES
1. Inhalation Carcinogenesis. AEC Symposium Series No. 18, CONF-
691001. Available from NTIS. 1970.
2. Lundin, Jr., F. E., J. K. Wagoner, and V. E. Archer. Radon
daughter exposure and respiratory cancer: Quantitative and
temporal aspects. NIOSH-NIEHS Joint Monograph No. 1, Public
Health Service, DHEW. 1971.
3. Jacobi, W. Dose to the human respiratory tract by inhalation of
short-lived radon-222- and radon-220-decay products. Health Phys.
10_: 1163-1174, 1964.
4. Radford, Jr., E. P., and V. R. Hunt. Polonium-210 a volatile
radioelement in cigarettes. Science 143:247-249, January 17,
1964.
5. Black, S. C. and E. W. Bretthauer. Polonium-210 in tobacco. Rad.
Health Data Rpts. 9_: 145-152, 1968.
6. Bretthauer, E. W. and S. C. Black. Polonium-210: Removal from
smoke by resin filters. Science 156:1375-1376, June 9, 1967.
7. Curtis, M. R., F. D. Bullock, and W. F. Dunning. A statistical
study of the occurrence of spontaneous tumors in a large colony of
rats. J. Cancer Res. 15_:67-121, 1931.
8. Ratcliffe, H. L. The Rat in Laboratory Investigation. E. J.
Farris and J. Q, Griffith, Eds. Hafner Publishing Co., New York.
pp. 522-523, 1963.
9. Guyton, A. C. Am. J. Physiol. 150;70, 1947.
10. Bretthauer, E. W., S. C. Black, R. L. Satterwhite, E. Compton, and
A. A. Moghissi. An inhalation device for exposing rats to ciga-
rette smoke. Arch. Environ. Health 25:456-458, 1972.
11. Task group on lung dynamics. ICRP Committee II. Health Phys. 12;
173-207, 1966.
12. Thomas, R. G. and J. N. Stannard. Distribution and excretion of
polonium-210. VI. After intratracheal administration in the rat.
Radiation Res., Suppl. 5:106-123, 1964.
11
-------
13. Casarett, L. J. Distribution and excretion of polonium-210. IX.
Deposition, retention and fate after inhalation by "nose-only"
exposure. Radiation Res., Suppl. 5:148-165, 1964.
14. Yuile, C. L., H. L. Berke, and T. Hull. Lung cancer following
polonium-210 inhalation in rats. Radiation Res. 31:760-774, 1967.
15. Grossman, B. N., J. B. Little, and W. F. O'Toole. Role of carrier
particles in the induction of bronchial cancer in hamsters by
polonium-210 alpha radiation. Presented at Radiation Research So-
ciety Annual Meeting, May 9-13, 1971.
16. Saffiotti, U., F. Cefis, and L. H. Kolb. A method for the experi-
mental induction of bronchogenic carcinoma. Cancer Res. 28;104-
124, 1968.
17. Auerbach, 0., E. C. Hammond, D. Kirkman, and L. Garfinkel. Effects
of cigarette smoking on dogs. II. Pulmonary neoplasms. Arch.
Environ. Health 21:754-768, 1970.
12
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TECHNICAL REPORT DATA
(Please read Instructions on the reverse before completing)
1. REPORT NO.
EPA-680/1-75-001
2.
3. RECIPIENT'S ACCESSION NO.
4. TITLE AND SUBTITLE
SYNERGISTIC EFFECT OF POLONIUM-210 AND CIGARETTE
SMOKE IN RATS
5. REPORT DATE
June 1975
6. PERFORMING ORGANIZATION CODE
7. AUTHOR(S)
Stuart C. Black and Erich W. Bretthauer
8. PERFORMING ORGANIZATION REPORT NO.
9. PERFORMING ORG \NIZATION NAME AND ADDRESS
Monitoring Systems Research and Development Laboratory
National Environmental Research Center
P. O. Box 15027
Las Veaas. NV 89114
10. PROGRAM ELEMENT NO.
F11082
11. CONTRACT/GRANT NO.
ROAP 21 AMC
12. SPONSORING AGENCY NAME AND ADDRESS
Office of Research and Development
U.S. Environmental Protection Agency
Washington, DC 20460
13. TYPE OF REPORT AND PERIOD COVERED
FINAL
14. SPONSORING AGENCY CODE
15. SUPPLEMENTARY NOTES
16. ABSTRACT
An experimental procedure was devised to test the possible syner-
gistic effect of polonium-210 and cigarette smoke in rats. Appropriate
techniques were developed to expose the rats to cigarette smoke through
mouth-breathing and to add known amounts of polonium-210 to the cig-
arette smoke.
The findings from this experiment included: 1) lung deposition of
polonium-210 was 31 ± 2%, 2) early retention of polonium was two-
phased with half-times of 4 and 84 hours, and 3) bronchitis, emphysema
and lung tumors were observed in the experimental animals. Though the
spontaneous occurrence of two lung tumors in the number of animals at
risk was highly improbable, any conclusion that this resulted from the
exposure to cigarette smoke must be highly qualified.
17.
KEY WORDS AND DOCUMENT ANALYSIS
DESCRIPTORS
b.lDENTIFIERS/OPEN ENDED TERMS
c. COS AT I Field/Group
Polonium-210
Cigarette smoke
Cancer
Rats
Rodents
Carcinogenic effects
Radioactivity
Tobacco
Synergistic effects
0618
1802
18. DISTRIBUTION STATEMENT
Unlimited
19. SECURITY CLASS (ThisReport)
None
21. NO. OF PAGES
20. SECURITY CLASS (Thispage)
None
22. PRICE
EPA Form 2220-1 (9-73)
GPO 693-741/61
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