Tobacco Documents Online

r: . © Summary Epidemiologic data have long linked smoking with increased risk of cardiovascular disease, increased osteoporosis, amblyopia, and other disorders. Recent data demonstrate that smoking during pregnancy results in a greater risk of smaller birth weight and perinatal mortality among pregnant women. Smoking causes changes in plasma and leukocyte concentrations of vitamin C and impairs biochemical functions of this vitamin. Vitamin B12 is metabolized in the detoxifica- tion process of cyanide derived from smoking. Some heavy smokers develop an amblyopia which is reversed by either vitamin B,z supplementation or termination of smoking. Evidence is also presented suggesting that smoking may alter the metabolism of lipids, carbohy- drates, proteins, and other vitamins such as vitamin B6. 12-68' 0

Nutrient Interactions: References (1) AGAMANOLIS, D.P., CHESTER, E.M., VICTOR, M., KARK, J.A., HINES, J.D., HARRIS, J.W. Ncuropathology of experimental vitamin B-12 deficiency in monkeys. Neurology 26(10): 905-914„October 1976. (2) AINLEY, R.G. The Farnsworth-Munsell 100 hue test in tobacco amblyopia. Transaetions of the Ophthalmological Society of the United Kingdom 90: 765- 772, 1970. (3) ALBANESE, A.A., ORTO, L.A., WEIN„ E:H., ZAVATTARO, D.N. Effect of cigarette smoking on protein and' amino acid metabolism. I. Tryptophan. Nutrition Reports International 5(4): 245-2580 April 1972. (4), ANDREWS, J!, MCGARRY, J.M. A community study of smoking in pregnancy. The Journal of Obstetrics an& Gynaecology of the British Commonwealth 79(12): 1057-1073;,December 1972. (5) ARMSTRONG, B., LEA, A.J., ADELSTEIN, A.M., DONOVAN, J.W.,,WHITE, G.C. RUTTLE, S. Cancer mortality and saccharin consumption in diabetics. British Journal of Prevent7ve and Social Medicine 30(3); 151457, September 1976. (6) BAILEY, D.A., CARRON, A.V., TEECE, R.G., WEHNER, H.J. Vitamin C: supplementation related to physiological response to exercise in smoking and nonsmoking subjects. American Journal of Clinical Nutrition 23(7): 905-912,. July 1970. (7) , BRITISH MEDICAL JOURNALa Cigarette smoking in pregnancy. British Medical Journal2(6034)1492, August 28, 1976. (8): BRITISH MEDICAL JOURNAL. Smokers'' bones; British Medical Journal 2(8029): 201, Jnly 24; 1976. (9) BURR, M.L., ELWOOD, P.C., HOLE, D.J., HURLEY, R.J., HUGHES, R.E. Plasma and leukocyte ascorbic acid levels in the elderly. American Journal of Clinical Nutrition 27(2): 144-151~ February 1974. (10) BURR, R.G., RAJAN, K.T. Leucocyte ascorbic acid and pressure sores in paraplegia: British Journal of Nutrition 28(2): 275-281,1972. (11) CANADIAN MEDICAL ASSOCIATION JOURNAL. Tobacco amblyopia. Canadian, Medical Association Journal 102(4): 420; February 1970. (Editorial) (12) CHAMOT, A.P.H. BAZARBACHI, H~ Agents toxiques et grossesse (Toxicc agents and pregnancy). Gynaecologia 168(5): 318-327;1969. (13) CHISHOLM, I.A.,, PETTIGREW, A.R. Biochemical' observations in toxic optic neuropathy. Transactions of the Ophthalmological Society of the United Kingdom 90: 827-838, 1970. (14) CLEGG, K.M., MACDONALD, J.M. Irascorbic acid andA-isoascorbic acid in a common cold survey. American, Journal of Clinical Nutrition 28(9): 973-976, September 1975. (15) CREWS, S.J., JAMES, B., MARSTERS, 1B., WEST, R,H. Drug and nutritional factors in optic neuropathy. Transactions of the Ophthalmological Society of the United Kingdom 90: 773-794„1970. (16) CROSBY, W:M., METCOF:F, J., COSTILOE, J.P., MAMEES~fl, M., SAND- STEAD;, H.H., JACOB, R.A., MCCLAIN; P.E., JACOBSON; G., REID, W., BURNS, G. Fetal malnutrition: An appraisal of correlated factors. American Journal of Obstetrics and Gynecology 128(1): 22-31, May 1, 1977. (17) DASTUR, D;K., QUADROS, E.V., WADIA, N.H., DESAI, M.M.,,BHARUCHA, E.P. Effect of vegetarianism and smoking on vitamin~ B-12, thiocyanate, and folate levels in the blood ofi normal subjects. British Medical Journal 3: 260- 263, July 29;1972. 12-69

(18) DELAHAYE, J.P., BESSET C„TOUBOUL, P. Evolution apontanee et pronostic des arteriopathies atherosclereuses des membres inferieurs (Spontaneous evolution and prognosis of atherosclerotic arterial diseases of the lower limbs):. Archives des Maladies du Coeur et des Vaisseaux 63' (Supplement 1): 64-78, 1970. (19) DEWHURST,,F., KITCHEN„D.A. Effect of some 6-substituted benzo(a)pyrene derivatives upon liver enzymes and ascorbic acid'excretion in mice. Biochemi- cal Pharmacology22(7); 789-796, April 1973. (20) ELWOOD, P:C., HUGHES, R:E., HURLEY, R.J. Ascorbic acid and serum- cholesterol. Lancet 2(7684): 1197; December 5, 1970. (21) EL-ZOGHBY, S.M., EL-SHAFEI, A.K., ABDEL-TAWAB; G.A., KELADA, F.S. Studies om the effect'of reserpine therapy on the functional capacity, of the tryptophan-niacin pathway im smoker an& non-smoker males. Biochemical Pharmacology 19(5): 1661-1667,,May 1970. - (22) ~ FOULDS, W.S. Visual disturbances in systemic disorders, optic neuropathy, and systemic disease. Transactions of the Ophthaltnological Society of the United Kingdom„1969 Session, 89: 125-146, 1970. (28) FREEMAN, A.G. Thiocyanate metabolism in, human vitamin B-12 deficiency. British Medical Journal 1(5847)': 231-232, January 27;1973. (24) GASTARD, J., JOUBAUD,,F., FARBOS, T., LOUSSOUARN„J.,,MARION, 1 PANNIER, M.,,RENAUDET;,F., VALDAZO,.R., GOSSELIN, M. Etiology and course of primary chronic pancreatitis in Western France. Digestion 9(5): 416- 428,1973. (25) GRANT, F:W.,,COWEN, M.A., OZERENGIN, M.F., BIGELOW,,N. Nutritionali requirements in, mental illness. 1. Ascorbic acid retention in schizophrenia. A reexamination, Biological Psychiatry 5(3): 289-294, December 1972. (26): HALAWA, B., MAZUREK, W. Wplyw palenia tytoniu na poziom witaminy B-12 w surowicy u ludzi (Effect of Tobacco smoking on vitamin B-12 leveliin human serum). WiadomosciiLekarskie 29(6): 469-472, March 15, 1976. (27) HARRIS, J.O., SWENSON, E.W., JOHNSON, J.E. Human alveolar macro- phages: Comparison of' phagocytic ability, glucose utilization, an& ultrastruc- ture in smokers and nonsmokers. Journal of Clinical Investigation 49(11): 2086- 2096, November 1970. (28) HAUSER„G.A. Genussmittel in der schwangerschaft (Voluptuaries in pregnan- cy): Therapeutische Umschau 28(7) 430-434, July 1971. (29) HELMAN, N. Macrocytosis and cigarette smoking ('Letter). Annals of Internal! Medicine 79(2): 287,288, August 1973. (30) HUGH'ES,,R.E., JONES, P.R., NICHOLAS, P. Some effeets of experimentally- produced! cigarette smoke on the growth, vitamin C metabolism, and organ weights of guinea-pigs. Journal!of~ Pharmacy and Pharmacology 22(11): 823- 827, November 1970: (81) ILEBEKK, A., MILLER, N.E., MJOS, O.D. Effects of nicotine and inhalation of cigarette smoke on total body oxygen consumptioni in dogs. Scandinavian Journal of Clinical and Laboratory Investigation 35(1): 67-72, 1975. (32) JAYLE, G.E., METGE, P., CHAIX, A.,, VOLA, J!L., TASSY, A. Exploration fonctionnelle des nevrites optiques alboolo-t'abagiques (FunAional exploration of alcohol-tobacco optic neuritis): Archives D'Ophtalmoiogie 32(1); 79-86, 1972. (38), KAMPENG, V., VASINARAVONGSE, V., SIDDHIKOL„C:,Level of vitamin C in plasma in smokers and nonsmokers among medical students. Sibiraj; Hospital Gazette 25(6): 964-971, June 1973: (84)' KEITH~ M,O., PELLETIER, 0. The effect of~ nicotine on~ascorbic acid retention, by guineapigs: Canadian Journal of Physiology and 'Pharmacology 51(12): 879- 884; December 1973. 12-70

Y (85) KEVANY, J.,,JESSOP,, W., GOLDSMITH, A. The effect of smoking on ascorbic acid and serum cholesterol in adult! males. Irish Journal of Medical Science 144(12): 474-477, December 1975. (36) KNOX, D.L. Neuro-ophthalmology. Annual review. Archives of Ophthalmology 83(1): 103-127, January 1970. (39): KRISHNASWAMY, K., NADAMUNI NAIDU, A. Microsomal enzymes' in malnutrition as determined by plasma half life of antipyrine. British Medical' Journal 1(6060): 538-540, February 26, 1977. (38): LOH, H.S. Cigarette smoking an& the pathogenesis of atherosclerosis-a: hypothesis. Irish Journal ofi Medical Science 142(4): 174-178, July 1973. (8'9) LUBCHENCO, L.O. The infant who is small for gestational age. Major Problems in Clinical Pediatrics. Volume XIV. The High Risk Infant. Philadelphia, W.B. Saunders, 1976, pp. 181-201. (40): MCCLEAN, H.E:, DODDS, P.M., ABERNETHY, M.H., STEWART; A.W., BEAVEN,, D:VIF: Vitamin C concentration in plasma and leucocytes of inen~ related to age and smoking habit'. New Zealand'Medical Journal 83(561): 226- 229, ApriU14; 1976. (41) MCGARRY,, J.M., ANDREWS; J. Smoking in pregnancy and vitamin B-12 metabolism. British Medical Journal 2(5805): 74-77, April 18, 1971 (42): MITCHELL, D.A., SCHANDLa &K. Carbon monoxide, vitamin B-6, an& multiple sclerosis: a theory of interrelationship. American Journal of Clinical' Nutrition 26(8): 890-896, August 1973. (:43): MOLLER, E., KLEIN, B. Herzinfarkt und'subklinishcer diabetes (11lyocardiali infarct and subclinical diabetes). Medizinische Welt 21(26): 1191-1194, June 27;, 1970. (44) ORSETTI, A., AMARA, F., COLLARD, F., MIROUZE, J. Influence du tabac sur les hormones essentielles de 1a glycoregulation (The influence of tobacco: on~ hormones essential to glycoregulation). Nouvelle Press Medicale 4(21): 1571- 1572, May 24, 1975. (;4'5) PELLETIER, 0. Cigarette smoking and~ vitamin C. Nutrition Today 5(3): 12-15„ Autumn 1970: (46) PELLETIER, 0., Vitamin C and cigarette smokers. Annals of the New York Academy of Sciences 258: 156-168; 1975. (47) PELLETIER, 0. Vitamin C status of cigarette smokers and nonsmokers. American Journaliof ClinicaliNut'rition 23(5): 520-524; May 1970. (48) PELLETIER, 0.,,KEITH'y M.O. Bioavailability of synthetic and natural ascorbic acid. Journal of the American Dietetic Association 64(3): 271-275, March 1974. (49) PETTIGREW, A.R., FELL, G.S., CHISHOLM, LA. Red cell' gltrtathione im tobacco amblyopia. Experimental Eye Research 14(2): 87-90, 1972. (50) PHILLIPS, C.I., AINLEY, R.G., VAN PEBORGH, P.,, WATSON-WILLIAMS„ E>J.,, BOTTOMLEY„ A.C: Vitamin i B-12 content of aqueous humour. Nature 217(5123): 67-68, January 6, 1968. (51) POTTS, A.M. Tobacco amblyopia. Survey of Ophthalmology 17(5): 313-339;, March/Apri1,1973. (52) RATZMANN, K.-P.,, RIEMER, D., SPOERL, L., WEBER, L.,, WITTKOPF, E. Untersuchungen zur wirkung des zigaretten rauchens aut metaboliten des kodlenhyhrat-und fettstoffwechsels (Investigation of the effect of cigarette smoke on intermediates in carbohydrate: and lipid metabolism): Deutsche. Gesundheitswesen 34(28): 1618-1620, August 4, 1973. (58) ROBERTS, D.M. Chronic gastritis, alcohol,,and non-ulcer dyspepsia. Gut 13(10): 768-774, October 1972. (54) ROSSMANN', H. Vitamin B-12 resorption bei der sogenannten tabak-amblyopie. (Vitamin B-12 resorption in the so-called tobacco amblyopia). Deutsche Medizinische Wochenschrift 95(8): 419-420; February 20,1970:. 12-71

(55) SALAZAR, E., MORAGREGA, J.L., MAGOS, C., ZORRILLA, E„ SERRANO, P.A. Alteraciones metabolicas en sobrevivientes de infarto del miocardio (Metabolic changes in survivors of myocardial; infarction). Archivos del Instituto de Cardiologia de Mexico 43(1): 4-17, January/February 1973. (56) SCHETTLER, G., MOERL, H. Risikofaktoren der atherosklerose in beziehung zur lebenserwartung heute und den lebensaussichten morgan (Risk factors of atherosclerosis in relation to life expectancy today and in the future):, Medizinische Welt 27(46): 2201-2205, November 12,1976. (57) SCHRAUZER, G.N., LEE, L.P. The reduction of vitamin B-12a by carbon monoxide. Archives of Biochemistry and Biophysics 138(1); 16-25, May 1970. (58) SHANKAR,, R. Effect of chronic nicotine administration on the intestinal mucosal alkaline phosphatase in rats. Indian Journal of, Experimental Biology 13(4): 360-382, July 1975. (59) SILVERMAN, H.M. Fetal and newborn adverse drug reactions. A survey of the recent literature. Drug Intelligence and Clinical Pharmacy 8(12): 690-693, December 1974. (60) SIM, A.K. Ascorbic acid-a survey, past and present. Chemistry and Industry 8(4): 160-165, February 19, 1972. (61), SIMS, E.A.H. Experimental obesity, diet'ary-ind'uced thermogenesis;, and their clinical implications. Clinics in Endocrinology and Metabolism 5(2): 377-395, July 1976. (62)~ SPITTLE, C.R. The action of vitamin C on blood vessels. American Heart Journal 88(3): 387-388, September 1974. (63) SPITTLE, C.R. Atherosclerosis and vitamin C. Lancet 2(7737): 1280-1281, December 11, 1971. (64) SPRINCE, H., PARKER, C.M., SMITH, G.G., GONZALES, L.J. Protective action of ascorbic acid and'. sulfur compounds against acetaldehyde toxicity: Implications in alcoholism and smoking. Agents: and Actions 5(2): 164-173, 1975. (65) STRAUSS, L.H., SCHEER, P. Ueber die Einwirkungen des Nikotins auf den Vitamin C-Haushalt (On the influence of nicotine on the composition of vitamin C). Zeitschriflt fur Vitaminforschung 9: 39-48, 1939. (66) TAMURA, T., INOUE, H. IIDA, T., ONO, H. Studies on the antidotaliaction of drugs. Part 1. Vitamin C and its antidotal effect against alcoholic and nicotine poisoning. Journal of Nihon University Schooliof Dentistry 11: 149-151, 1969. (67) TOPORKOVA, LB. Vitamin C balance in connection with chronic exposure of tobacco industrial workers to tobacco dust. Leningradskii Sanitarno-Gigien- cheskii Meditsinskii Institut„Trudy 47: 243-?.53,1959. (68) TSARFIS, T.P.,, SVERDLOVA, P.S., ILYUSHINA, I.P., GLAZUNOV, I.S.,. METELITSA, V.I Disturbance in, tolerance to carbohydrates in males 50-59 years old. Terapevticheskii Arkhiv 41(12):,77-80;,December 1969. (69) WADIA, N.H., DESAI, M.M., QUADROS, E.V., DASTUR, D.K. Role of vegetarianism, smoking and hydroxocobalamin in optic neuritis. British Medical iJburnal 3: 264-267, July 29;,1972. (70) WELLS,, D.G., LANGMAN', M.J.S:,, WILSON, J. Thiocyanate metabolismi in human vitamin B-12 deficiency. British Medical Journal 4(5840): 588•590, December 9, 1972. + (71) WILSON, J., LINNELL, J!C., MATTHEWS, D.M. Plasma-cobalamins in neuro- ophthalmological'diseases. Lancet 1(7693): 259-261~ February 6,,1971! (72)' YEUNG„ D.L. Relationships between~ cigarette smoking, orall contraceptives,, and plasma vitamins A, E, C, and plasma: triglycerides and cholesterol.. AmericanJburnal of Clinical Nutritiom29(11); 121fr1221, November 1976. (73) YEW, M.-L.S., LO, Y. Levels of optimal vitamin C intake in individuals as estimated~ by the lingual tests. Proceedings of the Society for Experimental Biology and Medicine 144(2): 626-627, 1973. 12-72

Trace Constituents in Smoke Trace elements in~ tobacco that are sublimated at the temperature of smoking may interact with dietary components. These elements include organic compounds that are not pyrolyzed at these tempera- tures and compounds that may be formed during pyrolysis. The interaction may result because: cigarette smoke contains: (1) signifi- cant amounts of trace components normally present in the food; e:g., heavy metals, pesticides, and naturally occurring ca.rcinogens,, which may represent an important additionall source of exposure to these compounds; and (2) components that alter the metabolism of food' additives or constituents. Because of the large number of components that may occur in cigarette smoke, only those considered significant are discussed here. Trace Metals Nadkarnii (12), has reported that toxic elements in tobacco smoke include cadmium, lead, arsenic,, and selenium. Cadmium from cigarettes represents a very substantial additional burden for smokers when compared~ with that normally present in the diet and other non- industrial sources. For a person smoking two to three packs of cigarettes a day; the estimated~ respiratory cadmium intake ranges from 4 to 6 µg. The retention of cadmium via this route is high; it has been estimated that of the 4-6 µg of the cadmium in~the inhaled~ smoke, up to 2.82 µg would be absorbed. This represents a very significant exposure when compared with the proportion of cadmium retained from other sources, e.g., of 'the 50 µg/day cadmium~ ingested in food, retention may be of the order of only 3.0: µg. The significantly greater retention of cadmium by smokers is clearly reflected in greater levels of tissue cadmium in smokers compared to nonsmokers. Smokers accumulate more cadmium in the kidney cortex, liver, pancreas an& other tissues than nonsmokers (13); For a person smoking one pack of cigarettes a d'ay for 50 years, Elinder, et al. (5) estimated' an increase in body burden of cadmium of about 8 mg. In~ another study, Johnson, et all (9): estimated the body burden of cadmium~ in nonsmokers to be 10.3 mg compared'to 14.9 mg for smokers. Studies on the contribution of smoking to the body burden of other metals are limited. Cigarette smokers have been~ shown to have higher lead concentrations in the liver, pancreas, and kidney tissues, and slightly higher levels of lead in muscle and'fat than nonsmokers (6). Johnson, et al. (9) have reported that zinc and mercury concentrations were significantly higher in the pancreas and fat tissues of smokers, but lower in the kidney tissue than in the case of nonsmokers. z1oPolonium, which is present in the leaves of tobacco and volatizes at the temperature: at which cigarettes burn, is deposited in smoke particles and enters the lung with~the particles. The 210po concentration 12-73

I in cigarettes varies from 0.15 to 0.63 p Ci/g. Approximately 20 percent of the 210Po content of a: cigarette enters the lungs with the smoke stream, with one cigarette yielding about 0.08 p Ci of 210Po to the body: This is almost as much 210po as a person inhales from the atmosphere in 24 hours (14). There is no information to indicate that the increased body burden of these toxic elements results in toxic effects related to increased exposure to the elements: It is possible that subclinicali effects may occur, althoughi these effects cannot be demonstrated by the presently available methodology: Nitrosamines Tobacco smoke not only represents a source of exposure to nitrosable amines which can undergo nitrosation, but it is also a major source of exposure to preformed N-nitrosonornicotine (NNN), which is present in processed tobacco. Its concentration ranges from 0.3-90 ppm in smoking tobacco, chewing tobacco, and snuff. Hilfrich, et al. (8) have estimated exposure to NNN from tobacco smoke at 140-250 ng/cigarette. Fine (6) has estimated the exposure to nitrosamines from i tobacco smoke, primarily NNN, to be 4.1 pg/d'ay (from 20 cigarettes) compared~ to 6 µg/day (nitropyrollidine and~ other nitrosamines)~ from food! NNN induces tumors of the esophagus, pharynx, and the nasal cavity in rats, and it is possible that the increased incidence of cancer in tobacco smokers an& chewers may be related to: the carcinogenicity of this compound (5). In addition, it is not known if the possible carcinogenic action of this compound may be additive or may potentiate the effect of - nitrosamines occasionally found in the diet. Schmeltz, et al. (15) have detected NLnitrosodlethanolamine in cured tobacco at concentrations ranging from 0.1 to 173' ng/g. They postulate that it is derived from the use of diethanolamine, a solubilizing agent for the plant growth regulator, maleic hydrazide. Schmelt'z and Hoffmann (16) have reviewed the occurrence of nitrogen-containing compounds in tobacco and tobacco smoke. Included in the list of compounds reported are numerous aliphatic amines, notably secondary an& tertiary amines, as well as aromatic amines, which have the potential of being converted to nitrosamines in the presence of nitrite or nitrogen oxide. Because saliva normally contains low levels of nitrite (18), there is a potential for nitrosation of the amines to occur in vivo: In addition, nitrite in certain processed foods may represetit a source of nitrite for nitrosation of these amines. The synthesis of nitrosaminess may be further catalyzed by the presence of thiocyanate in saliva. Because thiocyanate levels are greatly increased in the saliva, as well as in t'he st'omach content, of smokers compared to that of nonsmokers, the potential for in vivo ~ nitrosation is greatly increased in smokers (5). However, other dietary components, e.g. ascorbic acid (1) or a- t S s n. 12-74

tocopherol (10), may reduce the potential for nitrosation, primariUy by reacting with the free nitrite. Nicotine is a major constituent of tobacco smoke; but Lijinsky and Singer (11) report that it is only very slowly nitrosated in aqueous solutions and thus does not provide a significant source for amines that may be nitrosated in the stoma& Pesticide Residues Atallah and Doroughi (.2) have reported on studies with cigarettes impregnated with 14Glabelled pesticides (carbaryl, carbofuran, lepto- phos, DDT, and mirex) and have provided information on, both the stability of these pesticides under smoking conditions as welli as the amount transferred to mainstream smoke. Mirex was reported to be the most stable compound (70 percent of 14C' in mainstream was unchanged mirex). Carbofuran was almost as stable as mirex. From,40 to 45 percent of the 14C' in mainstream smoke from carbaryU and DDT was in the form of the parent compound. Leptophos was the least stable, with only 21 percent of the 14C'in the mainstream smoke present as the parent compound. Rats which inhaled the 14C-labelled smoke derived from the: treated' cigarettes did not show patterns or tissue distribution of inhaled 14C-labelled pesticides which could be considered characteristic for a particular type of pesticide. In contrast, Atallah and Doroughi (2); cited a report by Guthrie (7) which states that carbamates an& organophosphate pesticides were almost completely degraded dkzring the smoking process. More information is needed' on the nature and ultimate fate of insecticide residues inhaled in tobacco smoke: Based on the information reviewed, it is not possible to assess the health significance of pesticide residues in tobacco. In addition to the active principals contained in pesticides, other subtances such as surfactants or solubiliQing, agents of inert carriers may, if transferred to tobacco smoke, interact with compounds in the diet or undergo conversion to potentially hazard'ous substances in the tobacco leaf itself, e.g., nitrosation of diethanolamine which is used as a solUbilizing agent for maleic hydrazide. Very little is known regarding these potential interactions and the effects, if any, in humans. There is also little information on the fate of N-containing agricultural chemicals after their application to tobacco. Maleic hydrazide is present in~ cured tobacco (20-30 ppm) and,a small portion (4-10 percent); is transferred unchanged to mainstream smoke. Metabolic Effects Constituents of tobacco smoke may inhibit or induce enzyme activity in human tissues and alter the rate of metabolism of food additives or food constituents. 12-75

Nicotine has been shown to cause significant reduction in rats' intestinal alkaline phosphatase activity. The significance of the reduced activity of this marker enzyme of intestinal mucosa is not known, but it may be indicative of a reduced metabolic activity of the mucosat cells. Shankar(17) has postulated that this may be one of the factors causing,sensit'ivities of mucosal i cells to acid destruction. A large number of polynuclear aromatic hydrocarbon (PNAs) have beeni identified in tobacco smoke: Wynder and Hoffmann (19)' have reported that the concentration of PNA in the smoke of one cigarette ranges from, 0.6-70.0 ng. In addition to their well-known effects as initiating carcinogens, PNAs are well-known inducers of mixed function oxidases. The effect of PNAs on the proliferation of microsomal enzymes and on subsequent increases in cytochrome P-450 has already been discussed' in detail. However, it is of interest to note that cigarettes contain substances that may depress the activity of microsomali enzymes at one site and increase them at another site, e.g., cigarette smoke depresses pulmonary aryl hydrocarbon hydroxylase (AHH) activity in guinea pigs but increases liver AHH act'ivity(3). The depression of pulmonary AHH activity may be due to the presence of carbon monoxide or cyanide in tobacco smoke combining directly with the cytochromes and rendering them unavailable for their role in, the enzymatic action. It' is not known if these metabolic changes can affect the metabolism of food chemicals or food constituents, or if the level of changes that can occur are significant in relation to the inhibition or increase of microsomal activity by normal dietary constituents or contaminants in the diet. Another area of concern relates to the possible effect of enzyme inducers of the developing fetus: Enzyme inducers that cross the placental barrier may effect changes in the enzyme patterns of the developing fetus. Such changes or biochemical imprints may persist throughout life and could possibly result in altered patterns of metabolism of food additives and contaminants. It is not known to what extent, if any, constituents of tobacco smoke may cause these changes. However, a major problem in evaluating any possible effect due to the constituents of tobacco smoke is the lack of knowledge of the quantitative aspect of the relative amounts and activities of the components in tobacco smoke compared! with those active substances normally present in the diet or present as contaminants (e.g., environmental contaminants, PCBs, DDT) of the diet„and the possible interactions betweenisuch compounds. .! Summary Although cigarette smoking will result in an additional body burden of Cd and Pb, there is little evidence that this will result in known adverse effects. The effects of nitrosamines and inhibitors and activators of enzymes in tobacco smoke have not been established. Ti ( ( ( (. (• (I (1 12-76

Trace Constituents in Smoke: References (1) ARCHER; M.C~, TANNENBAUM, S.R.,,FAN, T: Y.,,WEISMAN„M. Reactionof nitrite with ascorbate and its relation to nitrosamine formation. Journal of the National Cancer Institute, 54(5): 1203-1205, May 1975. (2) ATALLAH, Y.H., DOROUGH'y H.W. Insecticide residues in cigarette smoke. Transfer an& fate im rats.,Journal of Agriculture and Food Chemistry, 23(1)1 64-71,1975. (3) BILIMORIA, M,H., JOHNSON, J., HOGG, J.C., WITSCHI, H.P. Pulmonary aryl hydrocarbon hydroxylase: Tobacco smoke-exposed guinea pigs. Toxicology and Applied' Pharmacology 41: 433-440,1977. (4) BOYLAND, E., WALKER, S.A. Effect of thiocyanate on the nitrosation of amines. Nature, 248: 601-602; April 12,1974: (5) ELINDER„ C.G., KJELLSTROM, T., FRIBERG, L., LIND, B., LINNMAN, L. Cadmium in kidney cortex, liver, and pancreas from Swedish autopsies:. Archives of Environmental Health 31(6): 292-302, November/December 1976. (6), FINE, D.H. An assessment of human exposure to N-nitroso compounds. Presented at the Fifth meeting on Analysis and Formatiom of N-nitroso Compounds, International Agency for Research on Cancer, Durham, N.H,, August 22-24, 1977, 15 pp. (7) GUTHRIEj F.E. The nature and significance of pesticide residues on tobacco and in tobacco smoke. Beitrage zur Tabakforschung 4(6): 229-246, November 1968. (8) HILFRICH, J., HECHT, S.S,,,HOFFMANN„D. A studyof tobacco carcinogene- sis. XV. Effects of N'-nitrosonornicotine and N'-nitrosoanabasine in Syrian golden hamsters. Cancer Letters 2: 169-175, 1977: (9) JOHNSON, D.E., PREVOST,, R.J., TILLERY, J.B., THOMAS, R.E: The Distribution of Cadmium and Other Metals in Human ~ Tissue. San Antonio, Southwest Research Institute, September 1977, 231 pp. (10) KAMM, J.J., DASHMAN, T., NEWMARK, H., MERGENSi W.J. Inhibition of amine-nitrite hepatotoxicity by «-tocopheroll Toxicology and Applied Pharma- cology 41: 575-583, September 1977: (11) LIJINSKY, W., SINGER, G.M. Formation of nitrosamines from tertiary amines and nitrous acid; In: Bogovski, P. and' Walker, E.A. (Editors). N-Nitroso Compounds in the Environment. Proceedings of a Working Conference held at the International Agency for Research on Cancer, Lyon+ France, October 17- 20, 1973. Lyon, International! Agency for Research on Cancer, 1975, pp. 111- 114. (12) NADKARNI, R.A. Some considerations,of metal content of tobacco products. Chemist'ry and Industry 17: 693-696,,September 7,1974. (1S) OFFICE OF TOXIC SUBSTANCES. Multimedia Levels-Cadmium. Environ* mental Protection Agency, Office of Toxic Substances, September 1977, pp. 5- 1-5-214 6-143-14. (14) PARFENOV, Y.D. Polonium-210 in the environment and in the human organism. Atomic Energy Review 12(1): 75-143,1974. (13)i SCHMELTZ, I.,,ABIDI, S., HOFFMANN„D. Tumorigenic agents in unburned processed tobacco; N-Nitrosodiethanolamine and 1,1-Dimethylhydrazine. Cancer Letters 2: 125-131, 1977. (16) SCHMELTZ, I., HOFFMANN, D., Nitrogen-containing compounds in tobacco and tobacco smoke. ChemicaliReviews 77(3): 295-311, June 1977: (17) SHANKAR, R. Effect of chronic nicotine administration, on the intestinal mucosal alkaline phosphatase in rats: Indian Journaliof Experimental, Biology 13: !360-362, July 1975. (18) TANNENBAUM, S:R:, WEISMAN, M., FETT,, D. The effect of nitrate intake on nitrite format6on, in human saliva. Food and Cosmetics Toxicology (Oxford)~ 14: 549-552, 1976. 12-77