Science 1966 : Lead-210 and Polonium-210 in Tissues of Cigarette Smokers

Science 9 September 1966: 
 Vol. 153 no. 3741 pp. 1259-1260
DOI: 10.1126/science.153.3741.1259

Lead-210 and Polonium-210 in Tissues of Cigarette Smokers

1. Richard B. Holtzman,
2. Frank H. Ilcewicz
   

   Abstract

   Concentrations of lead-210 and polonium-210 in rib bones taken from 13 cigarette smokers were about twice those in six nonsmokers, the polonium-210 being close to radioactive equilibrium with the lead-210. In alveolar lung tissue the concentration of lead-210 in smokers was about twice that in nonsmokers. These differences are attributed to additional intake by inhalation of lead-210.
   
    http://www.sciencemag.org/content/153/3741/1259.short

Winters-TH, Franza-JR : Radioactivity in Cigarette Smoke

Winters-TH, Franza-JR, Radioactivity in Cigarette Smoke, New England Journal of Medicine, 1982; 306(6): 364-365

To the Editor: During the 17 years since the Surgeon General’s first report on smoking, intense research activity has been focused on the carcinogenic potential of the tar component of cigarette smoke. Only one definite chemical carcinogen — benzopyrene — has been found. Conspicuous because of its absence is research into the role of the radioactive component of cigarette smoke.
The alpha emitters polonium-210 and lead-210 are highly concentrated on tobacco trichomes and insoluble particles in cigarette smoke (1). The major source of the polonium is phosphate fertilizer, which is used in growing tobacco. The trichomes of the leaves concentrate the polonium, which persists when tobacco is dried and processed.
Levels of Po-210 were measured in cigarette smoke by Radford and Hunt (2) and in the bronchial epithelium of smokers and nonsmokers by Little et al. (3) After inhalation, ciliary action causes the insoluble radioactive particles to accumulate at the bifurcation of segmental bronchi, a common site of origin of bronchogenic carcinomas.
In a person smoking 1 1/2 packs of cigarettes per day, the radiation dose to the bronchial epithelium in areas of bifurcation is 8000 mrem per year — the equivalent of the dose to the skin from 300 x-ray films of the chest per year. This figure is comparable to total-body exposure to natural background radiation containing 80 mrem per year in someone living in the Boston area.
It is a common practive to assume that the exposure received from a radiation source is distributed throughout a tissue. In this way, a high level of exposure in a localized region — e.g. bronchial epithelium — is averaged out over the entire tissue mass, suggesting a low level of exposure. However, alpha particles have a range of only 40 um in the body. A cell nucleus of 5 to 6 um that is traversed by a single alpha particle receives a dose of 1000 rems. Thus, although the total tissue dose might be considered negligible, cells close to an alpha source receive high doses. The Po-210 alpha activity of cigarette smoke may be a very effective carcinogen if a multiple mutation mechanism is involved.
Radford and Hunt have determined that 75 per cent of the alpha activity of cigarette smoke enters the ambient air and is unabsorbed by the smoker, (2) making it available for deposit in the lungs of others. Little et al. have measured levels of Po-210 in the lungs of nonsmokers that may not be accounted for on the basis of natural exposure to this isotope.
The detrimental effects of tobacco smoke have been considerably underestimated, making it less likely that chemical carcinogens alone are responsible for the observed incidence of tobacco-related carcinoma. Alpha emitters in cigarette smoke result in appreciable radiation exposure to the bronchial epithelium of smokers and probably secondhand smokers. Alpha radiation is a possible etio- logic factor in tobacco-related carcinoma, and it deserves further study.
Thomas H. Winters, M.D.
Joseph R. Di Franza, M.D.
University of Massachusetts Medical Center
Worcester, Ma 01605
Footnotes:
1. Martell EA. Radioactivity of tobacco trichomes and insoluble cigarette smoke particles. Nature. 1974; 249:215-7.
2. Radford EP Jr, Hunt VR. Polonium-210: a volatile radioelement in cigarettes. Science. 1964; 143:247-9
3. Little JB, Radford EP Jr, McCombs HL, Hunt VR. Distribution of polonium-210 in pulmonary tissues of cigarette smokers. N Engl J Med. 1965; 273:1343-51.
NEJM 307(5):309-313.
To the Editor: In a letter in the Feb 11 issue, Winters and DiFranza (1) correctly point out that alpha radiation from polonium-210 is a possible causal factor in tobacco-related carcinoma, but they incorrectly state that “inhaled” Po210 is a factor and that research on this important possibility has been neglected. I will briefly review recent pertinent research.
Radford and Hunt (2) first suggested that alpha radiation from Po210 in cigarette smoke may be important in the genesis of bronchial cancer. Little et al. (3) found surprisingly high concentrations of Po210 at single bronchial bifurcations in seven of 37 cigarette smokers. Holtzman and others (4 – 6) raised doubts about the validity of these observations because inhaled volatile Po210 is soluble and rapidly cleared. Subsequently, I determined (7) that lead-210 (a beta-emitting precursor of Po210) is highly concentrated in tobacco trichomes and that trichome combustion in burning cigarettes produces insoluble, Pb210-enriched particles in mainstream smoke. Thus, the high concentrations of Po210 observed at segmental bifurcations (4 – 6) can be explained by the persistence of insoluble, Pb210-enriched particles deposited at bifurcations and by the ingrowth of Po210 in these particles. (7,8) Radford and Martell (9) confirmed that the excess Po210 in the bronchial epithelium of smokers is accomplished by a larger excess of Pb210.
Fleischer and Parungo (10) provided experimental evidence indicating that radon decay products and Pb210 are concentrated on trichome tips. Mechanisms of accumulation of Pb210 on tobacco trichomes are discussed by Martell and Poet. (11)
Two recent studies (12,13) indicate that alpha radiation from inhaled indoor radon progeny may explain the incidence of lung cancer in nonsmokers. Martell and Sweder (14) report that indoor radon decay products that pass from the room air through burning cigarettes into mainstream smoke are present in large, insoluble smoke particles that are selectively deposited at bifurcations. Thus, the smoker receives alpha radiation at bronchial bifurcations from these three sources: from indoor radon progeny inhaled between cigarettes, from Po214 in mainstream smoke particles, and from Po210 that grows into Pb210 enriched particles that persist at bifurcations. I estimate that the cumulative alpha dose at the bifurcations of smokers who die of lung cancer is about 80rad (1600rem) — a dose sufficient to induce malignant transformations by alpha interactions with basal cells.
Edward A Martell, Ph.D.
National Center for Atmospheric Research
Boulder, CO 80307
Footnotes:
1. Winters TH, DiFranza JR. Radioactivity in Cigarette Smoke. NEJM 1982 306:364-365
2. Radford EP, Hunt VR. Polonium-210: a volatile radioelement in cigarettes. Science. 1964; 143:247-249
3. Little JB, Radford EP, McCombs HL, Hunt VR. Distribution of polonium-210 in pulminary tissues of cigarette smokers. NEJM. 1965; 273:1343-1351
4. Holtzman RB, Ilcewicz FH. Lead-210 and polonium-210 in tissues of cigarette smokers. Science. 1966; 153:1259-1260
5. Little JB, Radford EP. Polonium-210 in bronchial epithelium of cigarette smokers. Science. 1967; 155:606
6. Holtzman RB. Polonium-210 in bronchial epithelium of cigarette smokers. Science. 1967; 155:607
7. Martell EA. Radioactivity in tobacco trichomes and insoluble cigarette smoke particles. Nature. 1974; 249:215-7
8. Martell EA. Tobacco radioactivity and cancer in smokers. Am Sci. 1975; 63:404-412
9. Radford EP, Martell EA. Polonium-210: lead-210 ratios as an index of residence times of insoluble particles from cigarette smoke in bronchial epithelium. In: Walton WH, ed. Inhaled particles, part 2. Oxford: Pergamon Press, 1977:567-580
10. Fleischer RL, Parungo FP. Aerosol particles on tobacco trichomes. Nature. 1974; 250:158-159
11. Martell EA, Poet SE. Radon Progeny on Biological Surfaces and their effects. In: Vohra KG, et al., eds. Proceedings, Bombay Symposium on Natural Radiation in the Environment. New Delhi: Wiley Eastern Ltd., 1982
12. Evans RD, Harley JH, Jacobi W, Mclean AS, Mills WA, Stewart CG. Estimate risk from environmental exposure to radon-222 and its decay products. Nature. 1981;290;98-100
13. Harley NH, Pasternack BS. A model for predicting lung cancer risks induced by environmental levels of radon daughters. Health Phys. 1981; 40:307-16.
14. Martell EA, Sweder KS. The roles of polonium isotopes in the etiology of lung cancer in cigarette smokers and uranium miners. In: Gomez M, ed. Proceedings of a symposium on radiation hazards in mining. New York: American Institute of Mining Engineers, 1982:383-389.
To the Editor: The presence of Po210 and Pb210 in cigarette smoke may help to explain a paradox found in smokers of low-tar, low-nicotine cigarettes.
Hammond et al. (1) noted that the number of deaths from lung cancer was greater in subjects who smoked 20 to 39 low-tar, low-nicotine cigarettes a day than in those who smoked one to 19 high-tar, high-nicotine cigarettes a day. Thus, the number of cigarettes smoked may be more important than their tar and nicotine content.
Two features of low-tar low-nicotine cigarettes that help to reduce the amounts of tar in inhaled smoke may have little effect or adverse effects on the amounts of Po210 and Pb210 in inhaled smoke. In the first place, the use of higher porosity paper and perforated filters may enhance the completeness of combustion. Although this may decrease the tar and nicotine content in inhaled smoke, it may increase the pyrolysis of trichomes, resulting in smoke particles with higher specific activities of Pb210. Secondly, cigarette filters have been shown to have no noticeable protective effect against Po210 inhalation. (2) If Po210 and Pb210 contribute to tobacco related cancer, then the number of cigarettes smoked may be more important than the tar or nicotine content.
Although intensive effort has been successful in producing low-tar, low-nicotine cigarettes, perhaps future research should be aimed toward the development of low Po210, low Pb210 cigarettes.
Jeffrey I. Cohen M.D.
Duke University Medical Center
Durham, NC 27710
Footnotes:
1. Hammond EC, Garfinkel L, Seidman H, Lew EA. Some Recent findings concerning cigarette smoking. In: Origins of Human Cancer. New York: Cold Spring Harbor Laboratory, 1977:101-112
2. Rajewski B, Stahlholfen W. Polonium-210 activity in the lungs of cigarette smokers. Nature. 1966; 209:1312-1313
To the Editor: Contrary to the contention of Winters and DiFranza that research into the carcinogenic potential of the radioactive component of cigarette smoke is conspicuous by its absence, we and others have studied and reported on this risk since the theory was first proposed by Radford and Hunt in 1964. (1) Within five years of the initial report that the radioactive alpha emitter Po210 was present in mainstream smoke and in samples of bronchial epithelium from cigarette smokers, results from over two dozen related studies were published. The source of the Po210 and Pb210 (The beta emitter Pb210 is the long lived precursor that supports the Po210) was investigated, (2) the contents of these nuclides in various tobaccos documented, (3) the fraction transferred to the mainstream or sidestream smoke (or both) determined, (4) and the concentration in the whole lungs of smokers and nonsmokers measured. (5)
Measurements made with cigarette smoke condensate demonstrate that although radium and thorium are also present in cigarette smoke, 99% of the alpha activity is from Po210. (6) Measurements of the whole lungs of smokers and exsmokers show that the inhaled Po210 is retained in the lower lung. (7)
A relatively new detection technique using nuclear-track-etch film has allowed us to determine the amount and microdistribution of alpha activity on the bronchial mucosa in fresh autopsy specemins. (8) We examined about one-fourth of the upper respiratory tract in each of seven persons (Three smokers, two exsmokers, and two nonsmokers). A few areas of slightly elevated alpha activity were found in each of the bronchial trees examined except that of one young smoker, in which efficient bronchial clearance would be expected. The average dose rate to the basal cells of the bronchial epithelium from alpha activity in these seven persons ranged from 2.0 to 40mrem per year. For comparison, the natural background dose from inhaled radon-daughter alpha activity is about 2000mrem per year. One area of a few square millimeters, containing markedly elevated activity, was found in the bronchii of an older smoker. This area could deliver an annual dose of about 20,000mrem, comparable to the results originally reported by Bradford and Hunt. This activity can lead to a lifetime dose similar to the alpha dose that appears to yield an elevated risk of lung cancer in underground miners. However, the total dose cannot be calculated, since the residence time of such an alpha emitting spot on the bronchial tree is not known.
The importance of proper assessment of the risk to cigarette smokers from radionuclides in the smoke cannot be overstated. In view of the present knowledge, it is improbable that a single area of a few square millimeters of high alpha activity in the bronchial tree is important. Nonetheless, Po210 is the only component in cigarette smoke tar that has produced cancers by itself in laboratory animals as a result of inhalation exposure. (9)
We firmly believe that the role of alpha radiation in tobacco related carcinogenesis deserves further study. The techniques to define its role in this disease are now available.
Beverly S. Cohen, Ph.D.
Naomi H. Harley, Ph.D.
New York University School of Medicine
New York, NY 10016
Footnotes:
1. Radford EP, Hunt R. Polonium-210: a volatile radioelement in cigarettes. Science. 1964; 143:247-249
2. Tso TC, Harley NH, Alexander LT. Source of Pb210 and Po210 in tobacco. Science. 1966; 153:880-882
3. Black SC, Bretthauer EW. Polonium in tobacco. Radiat Health Data Rep. 1968;9:145
4. Ferri ES, Christiansen H. Lead-210 in tobacco and cigarette smoke. Public Health Rep. 1967; 82:828
5. Hill CR. Polonium-210 in man. Nature 1965; 208:423-428
6. Cohen BS, Eisenbud M, Harley NH. Alpha radioactivity in cigarette smoke. Radiat Res. 1979;83:190-196
7. Cohen BS, Eisenbud M, Wrenn ME, Harley NH. Distribution of polonium-210 in the human lung. Radiat Res. 1979;79:162-168
8. Cohen BS, Eisenbud M, Harley NH. Measurement of the alpha activity on the mucosal surface of the human bronchial tree. Health Phys. 1980:619-632.
9. Yuille CL, Berke HL, Hull T. Lung cancer following Pb210 inhalation in rats. Radiat Res. 1967;31:760-774
To the Editor: The letter of Winters and DiFranza has renewed the earlier suggestion that the radioisotope Po210 may have an important role in the induction of lung cancer in smokers. In particular, it is claimed that the radionuclide may be deposited very inhomogeneously in the bronchial epithelium, in the form of a limited number of relatively “hot” particles, and that such hot particles may be much more effective carcinogenically than the same amount of radioactivity would be if it were more uniformly distributed. The basis of both these claims must be questioned.
Evidence on the question of the carcinogenicity of hot particles has been reviewed by the International Commission on Radiological Protection, (1) which found the actual situation to be just the reverse of that suggested by the correspondents. The evidence cited for the actual formation of hot particles (2) comes from a study of the Po210 in a series of several very small samples of bronchial epithelium (usually less than 25mg) collected from smokers’ lungs. In these measurements, the activities in individual samples were so low that for a proportion at least, only about 20 counts were recorded in a counting period of three to seven days against a background of 40 counts. Proper analysis of the statistical validity of these observations was not given by the original authors and is not possible from their reported data. Contrary evidence, not cited by the correspondents, is provided by a somewhat earlier paper (3) that reported the results of auto radiographic examination of excised segments of bronchial epithelium; this study found no evidence of surface concentrations of alpha activity of more than 0.01pCi per square centimeter, corresponding to a mean dose rate of about 10mrem per year. Finally, the correspondents’ suggestion that the “major source of the polonium is phosphate fertilizer” is not substantiated and is at variance with published data (3,4) indicating that it originates as atmospheric fallout of the decay products of natural radon-222.
C.R. Hill, M.D.
Institute of Cancer Research
Royal Marsden Hospital
Sutton, Surrey SM2 5PX,
England
Footnotes:
1. International Commission on Radiological Protection. Biological effects of inhaled radionuclides, ICRP Publication 31, Section G, 86-92. Ann ICRP. 1980;4 (No. 1/2)
2. Little JB, Radford EP, McCombs HL, Hunt VR. Distribution of polonium-210 in pulminary tissues of cigarette smokers. NEJM 1965;273:1343-1351
3. Hill CR. Polonium-210 in man. Nature. 1965; 208:423-428
4. Hill CR. Lead-210 and polonium-210 in grass. Nature, 1960; 187:211-212
To the Editor: The Surgeon General’s recent denunciation of tobacco smoking and the American Cancer Society’s pessimistic prognosis that lung cancer will be the number one cause of death from cancer in women by 1985 (1) provide timely emphasis on the recent NEJM letter on radioactive alpha emitters in tobacco smoke. Some of the further study encouraged by Winters and DiFranza has in fact been performed, yielding results far more foreboding than expected.
In two separate studies, Little et al. (2,3) have induced respiratory tumors in hamsters by intratracheal instillation of Po210 in various amounts down to less than one-fifth that inhaled by a heavy cigarette smoker (one who consumes two packs a day) during 25 years. The incidence of tumors at the lowest dose was 13%, including borderline carcinomas, and was 11% for frankly malignant tumors.
Contrary to the expected results of most radiobiologists, dose reduction did not result in either a constant dose-response ratio (the linear response hypothesis) or a larger dose-response ratio (The threshold or sigmoid hypothesis) but instead produced a marked decrease in the dose-response ratio. In one study, a reduction in activity from 0.700microCi of Po210 instilled to 0.00375microCi of Po210 instilled — about a two hundred-fold decrease — resulted in a decrease in the incidence of tumors from 61% to 13% (including borderline cases) — only a fourfold decrease.
This decrease in the dose-response ratio with decreasing dose has also been observed in other studies of the effects of low dose alpha radiation and other radiation particles with high linear energy transfer (LET). In a study of osteosarcoma induction by alpha radiation, Muller et al. (4) had over a 100-fold decrease in the dose-response ratio from their highest dose (1500rad) to their lowest dose (15rad). For neutron radiation, Rossi et al. (5) found similar results, with leukemia induction having the smallest dose-response ratio in the lowest dose in survivors of the atomic bomb. Similarly, Hall et al. (6) found that both dose protraction and dose reduction for neutron radiation increased the cell-lethality-dose ratio of hamster cells in vitro.
The importance of these results with low dose irradiation by high LET particles should not be overlooked. Doses in the range of several thousand to 10^5 rad have generally been necessary for the experimental induction of lung cancer by beta or gamma radiation (with low LET), (7,8) as compared with the studies by Little et al., in which the lowest dose of 15rad (0.00375microCi in the lung volume for the lifetime of the hamsters) induced cancer at an incidence of about 13%.
Presumably, the high density of ionization along the track of alpha radiation (about one ion pair for every 2 Angstrom traveled) and other high-LET radiation is the prime factor causing Po210 to be an extremely efficient carcinogen.
Clearly, further work is warranted in this area, but we should not hesitate to disseminate the information already at hand — that the alpha-radiation exposure to the lungs of tobacco smokers is extremely important.
Walter L. Wagner, B.A.
Veterans Administration
Medical Center
San Francisco, CA 94121
Footnotes:
1. American Cancer Society. Ca: a cancer journal for clinicians. Jan/Feb 1981;Vol 31, No. 1
2. Little JB, Kennedy AR, McGandy RB. Lung cancer induced in hamsters by low doses of alpha radiation from polonium-210. Science. 1975; 188:737-738
3. Little JB, O’Toole WF. Respiratory tract tumors in hamsters induced by benz(a)pyrene and Po210 radiation. Cancer Res. 1974; 34:3026-3039
4. Muller WA, Gossner W, Hug O, Luz A. Late effects after incorporation of the short-lived alpha-emitters Ra224 and Th227 in mice. Health Phys. 1978; 35:33-55
5. Rossi HH, Mays CW. Leukemia risk from neutrons. Health Phys. 1978; 34:355-360
6. Hall EJ, Rossi HH, Roizin LA. Low-dose-rate irradiation of mammalian cells with radium and californium-252. Radiology. 1971; 99:445-451
7. Cember H. Radiogenic Lung Cancer. Prog Exp Tumor Res. 1964; 4:251.
8. Sanders CL, Thompson RC, Blair WJ. CITE>AEC Symp Ser. 1970; 18:285.
To the editor: The letter by Winters and DiFranza rivets much needed attention on the earlier finding of Radford and Hunt, (1) which is crucial to an understanding of the pathogenesis of smoking diseases. (2,3)

Although Winters and DiFranza tellingly describe the mechanisms by which Po210 on insoluble particles in cigarette smoke causes lung cancer, they neglect the even more important matter of how Po210 and other mutagens from tobacco smoke cause malignant neoplasms, degenerative cardiovascular diseases, and other diseases throughout the body of smokers (Table 1).
TABLE 1.
Effects of Smoking on Tissues Directly and Indirectly Exposed to Radiation in Current Cigarette Smokers*
Cause of Death Number of Deaths Observed/Expected (ratio)
Observed Expected
All causes 36,143 20,857 1.73
Emphysema 1,201 81 14.83
Cancer:
Of directly exposed tissue 3,061 296 10.34
- Of buccal cavity 110 26 4.23
- Of pharynx 92 7 13.14
- Of larynx 94 8 11.75
- Of lung and bronchus 2,609 231 11.29
- Of esophagus 156 24 6.50
Of indirectly exposed tissue 4,547 3,292 1.38
- Of stomach 390 257 1.52
- Of intestines 662 597 1.11
- Of rectum 239 215 1.11
- Of liver and biliary passages 176 75 2.35
- Of pancreas 459 256 1.79
- Of prostate 660 504 1.31
- Of kidney 175 124 1.41
- Of bladder 326 151 2.16
- Of brain 160 152 1.05
- Malignant lymphomas 370 347 1.07
- Leukemias 333 207 1.61
- All other cancers 597 407 1.47
All cardiovascular diseases 21,413 13,572 1.58
- Coronary heart disease 13,845 8,787 1.58
- Aortic aneurysm 900 172 5.23
- Cor pulmonale 44 8 5.50
- All other cardiovascular 6,624 4,605 1.44
Ulcer of stomach, duodenum or jejenum 289 93 3.10
Cirrhosis of liver 404 150 2.69
*Data adapted from Rogot and Murray. (4)

Volatilized, soluble Po210, produced at the burning temperature of cigarettes, (1) is cleared from the bronchial mucosa at the expense of the rest of the body, being absorbed through the pulmonary circulation and carried by the systemic circulation to every tissue and cell, causing mutations of cellular genetic structures, deviation of cellular characteristics from their optimal normal state, accelerated aging, and early death from a body-wide spectrum of diseases, reminiscent of the disease and mortality patterns afflicting early radiologists and others with long-term exposure to x-rays and other forms of ionizing radiation. (5,6)

The proof of circulating mutagens from smoking is that Po210 and other mutagens can be recovered not only from tobacco smoke and bronchial mucosa, but also from the blood and urine of smokers. (1,7)

R.T. Ravenholt M.D., M.P.H.
Centers For Disease Control
Washington Office
Rockville, MD 20857
Footnotes:
1. Radford EP Jr, Hunt VR. Polonium-210: a volatile radioelement in cigarettes. Science. 1964; 143:247-249
2. Ravenholt RT. Malignant cellular evolution: an analysis of the causation and prevention of cancer. Lancet. 1966; 1:523-526
3. Ravenholt RT, Lavinski MJ, Nellist D, Takenaga M. Effects of smoking upon reproduction. Am J Obstet Gynecol. 1966; 96:267-281
4. Rogot E., Murray JL. Smoking and causes of death among U.S. veterans: 16 years of observation. Public Health Rep. 1980:213-222
5. Warren S. Longevity and causes of death from irradiation in physicians. JAMA. 1956; 162:464-468
6. National Academy of Sciences-National Research Council. Long term effects of ionizing radiation from external sources. Washington D.C.: National Research Council, 1961.
7. Office on Smoking and Health. Smoking and Health: a report of the Surgeon General. Rockville, MD: Office on smoking and health, 1979. (DHEW publication no. [PHS]79-50066).
To the editor: We concur with Drs. Winters and DiFranza that the scientific and medical community as well as public health officials should be more concerned with the detrimental effects of cigarette smoking. Reviews on the carcinogenic effect of cigarette smoke are made available to United States physicians at regular intervals through the Surgeon General’s reports entitled Smoking and Health. (1) From these reports it is clear that benzo(a)pyrene is by far not the only carcinogen identified in cigarette smoke. Benzo(a)pyrene serves merely as an indicator for the wide spectrum of carcinogenic polycyclic hydrocarbons, all of which are pyro synthesized by the same mechanism during smoking. Aside from these hydrocarbons, cigarette smoke contains other carcinogens such as aza-arenes, aromatic amines (including beta-napthylamine), nickel, volatile nitrosamines, and especially tobacco-specific N-nitrosamines. (1-3) The N-nitrsamine compounds are formed by nitrosation of nicotine and other alkaloids; their concentrations in tobacco and smoke exceed those of nitrosamines found in other consumer products by at least several hundred fold. These nitrosamines are probably formed from nicotine in vivo. (2,3) Above all, one needs to consider that the carcinogenic potential of tobacco is a composite effect of tumor initiators, tumor promoters, or co-carcinogens, and organ-specific carcinogens. (1,2)
Dietrich Hoffmann, Ph.D.
Ernst L. Wynder, M.D.
American Health Foundation
New York, NY 10017
Footnotes:
1. Office on smoking and health. Smoking and Health: a report of the Surgeon General. Rockville, MD: Office on smoking and health, 1979. (DHEW Publication No. [PHS]79-50066)
2. Wynder EL, Hoffman D. Tobacco and health: a societal challenge. NEJM 1979; 300:894-903
3. Hofmann D, Adams JD, Brunnemann KD, Hecht DD. Formation, occurrence and carcinogenesity of N-nitrosamines in tobacco products. Am. Chem. Soc. Symp. Ser. 1981; 174:247-273
To the editor: We thank Dr. Martell and Drs. Cohen and Harley for their reviews of the literature. Judging by the response to our original letter, research into the radioactive component has been in progress since the early 1960′s, but the existence of this research is largely unknown outside a small segment of the scientific community. We were gratified to receive hundreds of phone calls from smokers who quit on learning about the alpha radiation in cigarette smoke.
Hill examined the lungs of only two smokers old enough to have metaplastic lesions. In addition, he analyzed whole bronchial specemins weighing 5g to 15g, of which only 2% by weight was epithelium. His result of 0.007 pCi per gram of tissue is in reasonable agreement with Little’s result of 0.012pCi per gram of whole bronchus and thus does not disprove the existence of hot spots. In addition, the accumulation of Pb210 on tobacco leaves is from natural and unnatural radon-222 decay products and from phosphate fertilizers.
We thank Dr. Wagner for pointing out that alpha radiation now appears to be 1000 times more carcinogenic than gamma radiation. Standard practice reguards alpha radiation as only 10 to 20 times as carcinogenic as gamma radiation.
The growing list of malignant diseases associated with smoking, presented by Dr. Ravenholt, begs for causal explanation. Smokers have higher levels of Po210 in the lungs, bone blood and urine. (1-3) Higher levels of Po210 have been consistently found in smokers in the liver, kidney, spleen, pancreas, and gonads. (4,5) A study with an adequate number of subjects would probably demonstrate a significant difference. The Po210 must be strongly considered as a cause of these cancers.
Drs. Cohen and Harley report finding one “hot spot” on studying the alpha activity of alpha Po210 in tracheal autopsy specemins of seven people, three of whom were smokers. (6) This supports Little and his colleagues’ previous findings of :hot spots” in 7 out of 37 smokers.
We thank Drs. Hoffmann and Wynder for correcting us about the variety of chemical carcinogens present in cigarette smoke. It is possible that chemicals and Po210 act as cocarcinogens in the following manner. Chemical and possibly physical agents create metaplastic nonciliated epithilial lesions. Auerbach demonstrated such lesions in 100% of heavy smokers. (7) The Po210 present on insoluble particles gains entrance to epithelial cells in such non-ciliated areas of mucous stagnation. Ingrowth of Po210 from the decay of Pb210 results in high doses of alpha radiation to already metaplastic cells. (8) Continued smoking ensures a steady delivery of Pb210 to these stagnant sites. Little and his co-workers have demonstrated synergism between benzo(a)pyrene and Po210 in an animal model. (9)
In view of the potential role of alpha radiation in a variety of tobacco related neoplasias, we believe that this area deserves more intense research. We find it surprising that the National Cancer Institute, with an annual budget of $500 million, has no active grants on alpha radiation as a cause of lung cancer (National Cancer Institute: personal communication).
We have found when educating smokers that more are encouraged to quit as they learn of the presence of radiation in cigarette smoke.
Joseph R. DiFranza, M.D.
Thomas H. Winters, M.D.
University of Massachusetts Medical Center
Worcester, MA 01605
Footnotes:
1. Little JB, Radford EP Jr, McCombs HL, Hunt VR. Distribution of polonium-210 in pulminary tissues of cigarette smokers. NEJM 1965; 273:1343-1351
2. Radford EP Jr, Hunt VR. Polonium-210: a volatile radioelement in cigarettes. Science. 1964; 143:247-249
3. Holtzman RB, Ilcewicz FH. Lead 210 and Po210 in tissues of cigarette smokers. Science. 1966; 153:1259-1260
4. Blanchard RL. Concentrations of Pb210 and Po210 in human soft tissues. Health Phys. 1967; 13:625-632.
5. Hill CR. Polonium 210 in man. Nature. 1965; 208:423-428
6. Cohen BS, Eisenbud M, Harley NH. Measurement of the alpha radioactivity on the mucosal surface of the human bronchial tree. Health Phys. 1980; 619-32
7. Auerbach O, Stout AP, Hammond EC, Garfinkel L. Changes in bronchial epithelium in relation to cigarette smoking and in relation to lung cancer. NEJM 1961; 265:253-67
8. Radford EP, Martell EA. Polonium 210/Lead 210 ratios as an index of residence times of insoluble particles from cigarette smoke in bronchial epithelium. In: Walton WH, ed. Inhaled Particles. IV. Part 2, Oxford, Pergamon Press, 1977:567-580
9. Little JB, McGrandy RB, Kennedy AR. Interactions between polonium 210 alpha radiation, benzo(a)pyrene, and 0.9% NaCl instillations in the induction of experimental lung cancer. Cancer Res. 1978; 38:1929-1935.

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EPA : Tobacco Smoke

http://www.epa.gov/rpdweb00/sources/tobacco.html

Tobacco Smoke

While cigarette smoke is not an obvious source of radiation exposure, it contains small amounts of radioactive materials which smokers bring into their lungs as they inhale. The radioactive particles lodge in lung tissue and over time contribute a huge radiation dose. Radioactivity may be one of the key factors in lung cancer among smokers.
On this page:

• How many people are exposed to radioactivity in cigarettes?
• How does radioactive material get into a cigarette?
• What happens when I smoke a cigarette?
• Resources

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How many people are exposed to radioactivity in cigarettes?

According to the American Lung Association, there are about 48 million adult smokers in the U.S., and 4.8 million adolescent smokers. This means that the U.S., population, directly exposed to radioactivity in cigarette smoke, is approximately 53 million.
According to the Centers for Disease Control and Prevention, 80 percent of adult tobacco users started smoking as teens; 35 percent had become daily smokers by age 18. Thirty nine percent of adult smokers smoke one pack of cigarettes per day, and 20% smoke more than a pack a day.
Smoking is the number one cause of preventable death in the U.S., with 443,000 deaths, or 1 of every 5 deaths, in the United States each year. And, there are 123,000 lung cancer deaths annually attributed to smoking cigarettes. Nearly 1 of every 5 deaths is related to smoking, more than alcohol, car accidents, suicide, AIDS, homicide, and illegal drugs combined.
In addition to smokers, those exposed to secondhand or side-stream smoke have been shown to risk disease as well. In some studies, it has been found that side-stream or secondhand smoke is two to five times more concentrated in some carcinogens than the mainstream smoke inhaled by a smoker. Each year, approximately 3,400 nonsmoking adults die of lung cancer as a result of breathing the smoke of others’ cigarettes. Environmental tobacco smoke also causes an estimated 46,000 deaths from heart disease in people who are not current smokers. Secondhand smoke contains over 4,000 chemical compounds, including 69 known carcinogens such as formaldehyde, lead, arsenic, benzene, and radioactive polonium 210.

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How does radioactive material get into a cigarette?

The tobacco leaves used in making cigarettes contain radioactive material, particularly lead-210 and polonium-210. The radionuclide content of tobacco leaves depends heavily on soil conditions and fertilizer use.
Soils that contain elevated radium lead to high radon gas emanations rising into the growing tobacco crop. Radon rapidly decays into a series of solid, highly radioactive metals (radon decay products). These metals cling to dust particles which in turn are collected by the sticky tobacco leaves. The sticky compound that seeps from the trichomes is not water soluble, so the particles do not wash off in the rain. There they stay, through curing process, cutting, and manufacture into cigarettes.Lead-210 and Polonium-210 can be absorbed into tobacco leaves directly from the soil. But more importantly, fine, sticky hairs (called trichomes) on both sides of tobacco leaves grab airborne radioactive particles.
For example, phosphate fertilizers, favored by the tobacco industry, contain radium and its decay products (including lead-210 and polonium-210). When phosphate fertilizer is spread on tobacco fields year after year, the concentration of lead-210 and polonium-210 in the soil rises.

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What happens when I smoke a cigarette?

Research indicates that lead-210 and polonium-210 are present in tobacco smoke as it passes into the lung. The concentration of lead-210 and polonium-210 in tobacco leaf is relatively low, however, this low concentration can accumulate into very high concentrations in the lungs of smokers.
As it passes into the lungs, the smoke impacts the branches of the lung passages, called bronchioles, where the branches split. Tar from tobacco smoke builds up there, and traps lead-210 and polonium-210 against the sensitive tissues of the bronchioles. Studies show filters on ordinary commercial cigarette remove only a modest amount of radioactivity from the smoke inhaled into the lungs of smokers. Most of what is deposited is lead-210, but polonium-210 (whose half life is about 138 days) quickly grows in as the lead-210 (half life = 22.3 years) decays and becomes the dominant radionuclide. Over time, the concentration of polonium-210 directly on tissues of the bronchioles grows very high, and intense localized radiation doses can occur at the bronchioles.

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Resources

Cancer Facts & Figures 2008 August 2008 - American Cancer Society

Trends in Tobacco Use July 2011 - American Lung Association

Source of Lead-210 and Polonium-210 in Tobacco August 2008

2004 Surgeon General's Report—The Health Consequences of Smoking August 2008

The Health Consequences of Involuntary Exposure to Tobacco Smoke: A Report of the Surgeon General June 2006

Statement by American Cancer Society, American Lung Association, American Heart Association and Campaign for Tobacco-Free Kids March 2009

Radioactivity in Tobacco Leaves August 2008

US EPA on radioactive Tobacco

http://www.epa.gov/radtown/tobacco.html

Radiation in Tobacco

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Radiation in Tobacco (PDF)
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This page provides a brief overview of radiation in tobacco and its effect on smokers.
On this page:

• Overview
• Who is protecting you
• What can you do to protect yourself
• Resources

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Overview

Every year 440,000 people die in the US from tobacco use and smoke-related diseases, which is approximately 20% of all deaths in the United States. Cigarettes kill more Americans than alcohol, car accidents, suicide, AIDS, homicide, and illegal drugs combined.
While not an obvious source of radiation exposure, cigarette smokers inhale radioactive material that, over time, contribute large radiation dose to the lungs. Worse, smokers are not the only ones affected by the radiation in cigarettes. Second-hand can be just as harmful to nearby non-smokers.
Naturally-occurring radioactive minerals accumulate on the sticky surfaces of tobacco leaves as the plant grows, and these minerals remain on the leaves throughout the manufacturing process. Additionally, the use of the phosphate fertilizer Apatite – which contains radium, lead-210, and polonium-210 – also increases the amount of radiation in tobacco plants.
The radium that accumulates on the tobacco leaves predominantly emits alpha and gamma radiation. The lead-210 and polonium-210 particles lodge in the smoker’s lungs, where they accumulate for decades (lead-210 has a half-life of 22.3 years). The tar from tobacco builds up on the bronchioles and traps even more of these particles. Over time, these particles can damage the lungs and lead to lung cancer.

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Who is protecting you

U.S. Environmental Protection Agency (EPA)

EPA’s Indoor Environments program has a voluntary smoke-free home campaign to increase awareness of secondhand smoke and the health risks of smoking indoors.

U.S. Department of Health and Human Services (HHS)

The Office of the Surgeon General is responsible for warning labels on cigarettes and offers programs to help people stop smoking.
The Center for Disease Control (CDC) provides information on tobacco use, promotes disease prevention, and provides educational tools for communities to take action to protect nonsmokers from second-hand tobacco smoke in public places.

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What you can do to protect yourself

To reduce the adverse effects of radiation in tobacco products:

• Do not chew tobacco or smoke (especially cigarettes without filters)
• Minimize exposure to second-hand smoke

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Resources

Smoke Free Homes and Cars Program January 2009. U.S. Environmental Protection Agency This bilingual site provides information on second-hand smoke and creating a smoke-free environment, as well as access to bilingual materials on these topics.

Cigarette Smoking November 2003. American Cancer Society This site provides information on the health effects of smoking, nicotine addiction and the benefits of quitting.

Smoking & Tobacco Use October 2009. Centers for Disease Control and Prevention This site offers links to useful information and documents on smoking and prevention.

Tobacco Smoke May 2009. U.S. Environmental Protection Agency, Radiation Protection This page answers commonly asked questions about radioactive materials in cigarettes.

Radioactive tobacco

http://www.acsa2000.net/HealthAlert/radioactive_tobacco.html

 by David Malmo-Levine (02 Jan, 2002)

It's not tobacco's tar which kills, but the radiation! image: Adbusters Cannabis is often compared to tobacco, with the damage caused by smoking tobacco given as a reason to prohibit use of cannabis. Yet most of the harms caused by tobacco use are due not to tar, but to the use of radioactive fertilizers. Surprisingly, radiation seems to be the most dangerous and important factor behind tobacco lung damage. Radioactive fertilizer It's a well established but little known fact that commercially grown tobacco is contaminated with radiation. The major source of this radiation is phosphate fertilizer.1 The big tobacco companies all use chemical phosphate fertilizer, which is high in radioactive metals, year after year on the same soil. These metals build up in the soil, attach themselves to the resinous tobacco leaf and ride tobacco trichomes in tobacco smoke, gathering in small "hot spots" in the small-air passageways of the lungs.2 Tobacco is especially effective at absorbing radioactive elements from phosphate fertilizers, and also from naturally occurring radiation in the soil, air, and water.3 To grow what the tobacco industry calls "more flavorful" tobacco, US farmers use high-phosphate fertilizers. The phosphate is taken from a rock mineral, apatite, that is ground into powder, dissolved in acid and further processed. Apatite rock also contains radium, and the radioactive elements lead 210 and polonium 210. The radioactivity of common chemical fertilizer can be verified with a Geiger-Mueller counter and an open sack of everyday 13-13-13 type of fertilizer (or any other chemical fertilizer high in phosphate content).4 Conservative estimates put the level of radiation absorbed by a pack-and-a-half a day smoker at the equivalent of 300 chest X-rays every year.5 The Office of Radiation, Chemical & Biological Safety at Michigan State University reports that the radiation level for the same smoker was as high as 800 chest X-rays per year.6 Another report argues that a typical nicotine user might be getting the equivalent of almost 22,000 chest X-rays per year.7 US Surgeon General C Everett Koop stated on national television in 1990 that tobacco radiation is probably responsible for 90% of tobacco-related cancer.8 Dr RT Ravenholt, former director of World Health Surveys at the Centers for Disease Control, has stated that "Americans are exposed to far more radiation from tobacco smoke than from any other source."9 Researchers have induced cancer in animal test subjects that inhaled polonium 210, but were unable to cause cancer through the inhalation of any of the non-radioactive chemical carcinogens found in tobacco.10 The most potent non-radioactive chemical, benzopyrene, exists in cigarettes in amounts sufficient to account for only 1% of the cancer found in smokers.9 Smoke screen Surprisingly, the US National Cancer Institute, with an annual budget of $500 million, has no active grants for research on radiation as a cause of lung cancer.1 Tobacco smoking has been popular for centuries,11 but lung cancer rates have only increased significantly after the 1930's.12 In 1930 the lung cancer death rate for white US males was 3.8 per 100,000 people. By 1956 the rate had increased almost tenfold, to 31 per 100,000.13 Between 1938 and 1960, the level of polonium 210 in American tobacco tripled, commensurate with the increased use of chemical fertilizers.14 Publicly available internal memos of tobacco giant Philip Morris indicate that the tobacco corporation was well aware of radiation contamination in 1974, and that they had means to remove polonium from tobacco in 1980, by using ammonium phosphate as a fertilizer, instead of calcium phosphate. One memo describes switching to ammonium phosphate as a "valid but expensive point."15 Attorney Amos Hausner, son of the prosecutor who sent Nazi Adolf Eichmann to the gallows, is using these memos as evidence to fight the biggest lawsuit in Israel's history, to make one Israeli and six US tobacco companies pay up to $8 billion for allegedly poisoning Israelis with radioactive cigarettes.16 image: Adbusters Organic solutions The radioactive elements in phosphate fertilizers also make their way into our food and drink. Many food products, especially nuts, fruits, and leafy plants like tobacco absorb radioactive elements from the soil, and concentrate them within themselves.17 The fluorosilicic acid used to make the "fluoridated water" most of us get from our taps is made from various fluorine gases captured in pollution scrubbers during the manufacture of phosphate fertilizers. This fluoride solution put into our water for "strong teeth" also contains radioactive elements from the phosphate extraction.18 Although eating and drinking radioactive products is not beneficial, the most harmful and direct way to consume these elements is through smoking them.19 The unnecessary radiation delivered from soil-damaging, synthetic chemical fertilizers can easily be reduced through the use of alternative phosphate sources including organic fertilizers.20 In one test, an organic fertilizer appeared to emit less alpha radiation than a chemical fertilizer.21 More tests are needed to confirm this vital bit of harm-reduction information. Organic fertilizers such as organic vegetable compost, animal manure, wood ash and seaweed have proven to be sustainable and non-harmful to microbes, worms, farmers and eaters or smokers. Chemical phosphates may seem like a bargain compared to natural phosphorous, until you factor in the health and environmental costs. To ensure that cannabis remains the safest way to get high, we must always use organic fertilizers and non-toxic pesticides. We should also properly cure the buds, take advantage of high-potency breeding and use smart-smoking devices like vaporizers and double-chambered glass water bongs. These will all help to address concern over potential lung damage far more effectively than either a jail cell or a 12-step program. Tobacco smokers can also use this information to avoid radioactive brands of tobacco. American Spirit is one of a few companies that offers an organic line of cigarettes, and organic cigars are also available from a few companies. You can also grow your own tobacco, which is surprisingly easy and fun. Until the public has an accurate understanding of how phosphate fertilizers carry radiation, and why commercial tobacco causes lung cancer but cannabis does not, there will be many needless tobacco-related deaths, and increased resistance to the full legalization of marijuana. References 1. Winters, TH and Franza, JR. 'Radioactivity in Cigarette Smoke,' New England Journal of Medicine, 1982. 306(6): 364-365, web 2. Edward A Martell, PhD. 'Letter to the Editor,' New England Journal of Medicine, 1982. 307(5): 309-313, web 3. Ponte, Lowell. 'Radioactivity: The New-Found Danger in Cigarettes,' Reader's Digest, March 1986. pp. 123-127. 4. Kilthau, GF. 'Cancer risk in relation to radioactivity in tobacco,' Radiologic Technology, Vol 67, January 11, 1996, web 5. Maryland Department of Health & Mental Hygiene. Website, 2001, web 6. Office of Environmental Health and Safety, Utah State University. 'Cigarettes are a Major Source of Radiation Exposure,' Safety Line, Issue 33, Fall 1996, web 7. Nursing & Allied Healthweek, 1996, 8. Herer, Jack. The Emperor Wears No Clothes, 11th edition, 1998. p. 110, web 9. Litwak, Mark. 'Would You Still Rather Fight Than Switch?' Whole Life Times, April/May, 1985. pp 11, web 10. Yuille, CL; Berke, HL; Hull, T. 'Lung cancer following Pb210 inhalation in rats.' Radiation Res, 1967. 31:760-774. 11. Borio, Gene. Tobacco Timeline. Website, 2001, web 12. Taylor, Peter. The Smoke Ring. Pantheon Books, NY, 1984. pp. 2-3, web 13. Smith, Lendon, MD. 'There Ought to Be a Law,' Chiroweb.com, November 20, 1992, web 14. Marmorstein, J. 'Lung cancer: is the increasing incidence due to radioactive polonium in cigarettes?' South Medical Journal, February 1986. 79(2):145-50, web 15. Phillip Morris internal memo, April 2 1980. Available online at www.pmdocs.com, web 16. Goldin, Megan. "'Radioactive' cigarettes cited in Israeli lawsuit." Reuters, June 23, 2000. 17. Health Physics Society, 'Naturally occuring radioactive materials factsheet,' 1997. see also: Watters, RL. Hansen, WR. 'The hazards implication of the transfer of unsupported 210 Po from alkaline soil to plants,' Health Physics Journal, April 1970. 18(4):409-13, web and web 18. Glasser, George. 'Fluoride and the phosphate connection.' Earth Island Journal, earthisland.org, web 19. Watson, AP. 'Polonium-210 and Lead-210 in Food and Tobacco Products: A Review of Parameters and an Estimate of Potential Exposure and Dose.' Oak Ridge National Laboratory, 1983. Florida Institute of Phosphate Research. 20. Burnett, William; Schultz, Michael; Hull, Carter. 'Behavior of Radionuclides During Ammonocarbonation of Phosphogypsum.' Florida State University, Florida Institute of Phosphate Research. March, 1995, web 21. Hornby, Paul, Dr. Personal communication, 2001. • David Malmo-Levine: email dagreenmachine@excite.com • American Spirit: 1-800-332-5595; web www.nascigs.com

INSERM

INSERM : cancer-du-poumon

Agents Classified by the IARC Monographs, Group 1

Agents Classified by the IARC Monographs, Volumes 1–104

Groupes d’évaluation – Définitions
Groupe 1 : L’agent est cancérogène pour l’homme.
Cette catégorie est utilisée lorsque l'on dispose d'indications suffisantes de cancérogénicité pour l'homme. Exceptionnellement, un agent peut être placé dans cette catégorie lorsque les indications de cancérogénicité pour l'homme sont moins que suffisantes, mais que l’on dispose d’indications suffisantes de sa cancérogénicité pour l'animal de laboratoire et de données probantes, chez l’homme exposé, selon lesquelles l'agent suit un mécanisme de cancérogénicité pertinent.

CAS No Agent Group Volume Year
000075-07-0 Acetaldehyde associated with consumption of alcoholic
beverages 1 100E 2012
Acid mists, strong inorganic 1 54, 100F 2012
001402-68-2 Aflatoxins 1 56, 82, 100F 2012
Alcoholic beverages 1 44, 96, 100E 2012
Aluminium production 1 34, Sup 7,
100F 2012
000092-67-1 4-Aminobiphenyl 1 1, Sup 7, 99,
100F 2012
Areca nut 1 85, 100E 2012
000313-67-7
Aristolochic acid
(NB: Overall evaluation upgraded to Group 1 based on
mechanistic and other relevant data)
1 82, 100A 2012
000313-67-7 Aristolochic acid, plants containing 1 82, 100A 2012
007440-38-2 Arsenic and inorganic arsenic compounds 1 23, Sup 7,
100C 2012
001332-21-4
013768-00-8
012172-73-5
017068-78-9
012001-29-5
012001-28-4
014567-73-8
Asbestos (all forms, including actinolite, amosite,
anthophyllite, chrysotile, crocidolite, tremolite)
(NB: Mineral substances (e.g. talc or vermiculite) that
contain asbestos should also be regarded as
carcinogenic to humans.)
1 14, Sup 7,
100C 2012
Auramine production 1 Sup 7, 99,
100F 2012
000446-86-6 Azathioprine 1 26, Sup 7,
100A 2012
000071-43-2 Benzene 1 29, Sup 7.
100F 2012
000092-87-5 Benzidine 1 29, Sup 7,
99, 100F 2012
Benzidine, dyes metabolized to
(NB: Overall evaluation upgraded to Group 1 based on
mechanistic and other relevant data)
1 99, 100F 2012
000050-32-8
Benzo[a]pyrene
(NB: Overall evaluation upgraded to Group 1 based on
mechanistic and other relevant data)
1 92, 100F 2012
007440-41-7 Beryllium and beryllium compounds 1 58, 100C 2012
Betel quid with tobacco 1 85, 100E 2012
Betel quid without tobacco 1 85, 100E 2012
000542-88-1
000107-30-2
Bis(chloromethyl)ether; chloromethyl methyl ether
(technical-grade) 1 4, Sup 7,
100F 2012
000055-98-1 Busulfan 1 4, Sup 7,
100A 2012
000106-99-0 1,3-Butadiene 1 97, 100F 2012
007440-43-9 Cadmium and cadmium compounds 1 58, 100C 2012
000305-03-3 Chlorambucil 1 26, Sup 7,
100A 2012
000494-03-1 Chlornaphazine 1 4, Sup 7,
100A 2012
018540-29-9 Chromium (VI) compounds 1 49, 100C 2012
Clonorchis sinensis (infection with) 1 61, 100B 2012
Coal, indoor emissions from household combustion of 1 95, 100E 2012
Coal gasification 1 92, 100F 2012
008007-45-2 Coal-tar distillation 1 92, 100F 2012
065996-93-2 Coal-tar pitch 1 35, Sup 7,
100F 2012
Coke production 1 92, 100F 2012
000050-18-0
006055-19-2 Cyclophosphamide 1 26, Sup 7,
100A 2012
059865-13-3
079217-60-0 Cyclosporine 1 50, 100A 2012
000056-53-1 Diethylstilbestrol 1 21, Sup 7,
100A 2012
Epstein-Barr virus 1 70, 100B 2012
066733-21-9 Erionite 1 42, Sup 7,
100C 2012
Estrogen therapy, postmenopausal 1 72, 100A 2012
Estrogen-progestogen menopausal therapy (combined) 1 72, 91, 100A 2012
Estrogen-progestogen oral contraceptives (combined)
(NB: There is also convincing evidence in humans that
these agents confer a protective effect against cancer in
the endometrium and ovary)
1 72, 91, 100A 2012
000064-17-5 Ethanol in alcoholic beverages 1 96, 100E 2012
000075-21-8
Ethylene oxide
(NB: Overall evaluation upgraded to Group 1 based on
mechanistic and other relevant data)
1 97, 100F 2012
033419-42-0
Etoposide
(NB: Overall evaluation upgraded to Group 1 based on
mechanistic and other relevant data)
1 76, 100A 2012
033419-42-0
015663-27-1
011056-06-7
Etoposide in combination with cisplatin and bleomycin 1 76, 100A 2012
Fission products, including strontium-90 1 100D 2012
000050-00-0 Formaldehyde 1 88, 100F 2012
Haematite mining (underground) 1 1, Sup 7,
100D 2012
Helicobacter pylori (infection with) 1 61, 100B 2012
Hepatitis B virus (chronic infection with) 1 59, 100B 2012
Hepatitis C virus (chronic infection with) 1 59, 100B 2012
Human immunodeficiency virus type 1 (infection with) 1 67, 100B 2012
Human papillomavirus types 16, 18, 31, 33, 35, 39, 45,
51, 52, 56, 58, 59
(NB: The HPV types that have been classified as
carcinogenic to humans can differ by an order of
magnitude in risk for cervical cancer)
1 64, 90, 100B 2012
Human T-cell lymphotropic virus type I 1 67, 100B 2012
Ionizing radiation (all types) 1 100D 2012
Iron and steel founding (occupational exposure during) 1 34, Sup 7,
100F 2012
Isopropyl alcohol manufacture using strong acids 1 Sup 7, 100F 2012
Kaposi sarcoma herpesvirus 1 70, 100B 2012
CAS No Agent Group Volume Year
Leather dust 1 100C 2012
Magenta production 1 57, 99, 100F 2012
000148-82-3 Melphalan 1 9, Sup 7,
100A 2012
000298-81-7 Methoxsalen (8-methoxypsoralen) plus ultraviolet A
radiation 1 24, Sup 7,
100A 2012
000101-14-4
4,4'-Methylenebis(2-chloroaniline) (MOCA)
(NB: Overall evaluation upgraded to Group 1 based on
mechanistic and other relevant data)
1 57, 99, 100F 2012
Mineral oils, untreated or mildly treated 1 33, Sup 7,
100F 2012
MOPP and other combined chemotherapy including
alkylating agents 1 Sup 7, 100A 2012
000091-59-8 2-Naphthylamine 1 4, Sup 7, 99,
100F 2012
Neutron radiation
(NB: Overall evaluation upgraded to Group 1 with
supporting evidence from other relevant data)
1 75, 100D 2012
Nickel compounds 1 49, 100C 2012
016543-55-8
064091-91-4
N'-Nitrosonornicotine (NNN) and 4-(NNitrosomethylamino)-
1-(3-pyridyl)-1-butanone (NNK)
(NB: Overall evaluation upgraded to Group 1 based on
mechanistic and other relevant data)
1 89, 100E 2012
Opisthorchis viverrini (infection with) 1 61, 100B 2012
Painter (occupational exposure as a) 1 47, 98, 100F 2012
057465-28-8
3,4,5,3’,4’-Pentachlorobiphenyl (PCB-126)
(NB: Overall evaluation upgraded to Group 1 based on
mechanistic and other relevant data)
1 100F 2012
057117-31-4
2,3,4,7,8-Pentachlorodibenzofuran
(NB: Overall evaluation upgraded to Group 1 based on
mechanistic and other relevant data)
1 100F 2012
000062-44-2
Phenacetin
(NB: Overall evaluation upgraded to Group 1 with
supporting evidence from other relevant data)
1 24, Sup 7,
100A 2012
Phenacetin, analgesic mixtures containing 1 Sup 7, 100A 2012
014596-37-3 Phosphorus-32, as phosphate 1 78, 100D 2012
007440-07-5 Plutonium 1 78, 100D 2012
Radioiodines, including iodine-131 1 78, 100D 2012
Radionuclides, alpha-particle-emitting, internally
deposited
(NB: Specific radionuclides for which there is sufficient
evidence in humans are also listed individually as
Group 1 agents)
1 78, 100D 2012
Radionuclides, beta-particle-emitting, internally deposited
(NB: Specific radionuclides for which there is sufficient
evidence in humans are also listed individually as
Group 1 agents)
1 78, 100D 2012
013233-32-4 Radium-224 and its decay products 1 78, 100D 2012
013982-63-3 Radium-226 and its decay products 1 78, 100D 2012
015262-20-1 Radium-228 and its decay products 1 78, 100D 2012
010043-92-2 Radon-222 and its decay products 1 43, 78, 100D 2012
Rubber manufacturing industry 1 28, Sup 7,
100F 2012
CAS No Agent Group Volume Year
Salted fish, Chinese-style 1 56, 100E 2012
Schistosoma haematobium (infection with) 1 61, 100B 2012
013909-09-6 Semustine [1-(2-Chloroethyl)-3-(4-methylcyclohexyl)-1-
nitrosourea, Methyl-CCNU] 1 Sup 7, 100A 2012
068308-34-9 Shale oils 1 35, Sup 7,
100F 2012
014808-60-7 Silica dust, crystalline, in the form of quartz or cristobalite 1 68, 100C 2012
Solar radiation 1 55, 100D 2012
Soot (as found in occupational exposure of chimney
sweeps) 1 35, Sup 7,
100F 2012
000505-60-2 Sulfur mustard 1 9, Sup 7,
100F 2012
010540-29-1
Tamoxifen
(NB: There is also conclusive evidence that tamoxifen
reduces the risk of contralateral breast cancer in breast
cancer patients)
1 66, 100A 2012
001746-01-6 2,3,7,8-Tetrachlorodibenzo-para-dioxin 1 69, 100F 2012
000052-24-4 Thiotepa 1 50, 100A 2012
007440-29-1 Thorium-232 and its decay products 1 78, 100D 2012
Tobacco, smokeless 1 89, 100E 2012
Tobacco smoke, second-hand 1 83, 100E 2012
Tobacco smoking 1 83, 100E 2012
000095-53-4 ortho-Toluidine 1 77, 99, 100F 2012
000299-75-2 Treosulfan 1 26, Sup 7,
100A 2012
Ultraviolet radiation (wavelengths 100-400 nm,
encompassing UVA, UVB, and UVC) 1 100D 2012
Ultraviolet-emitting tanning devices 1 100D 2012
000075-01-4 Vinyl chloride 1 97, 100F 2012
Wood dust 1 62, 100C 2012
X- and Gamma-Radiation 1