borderline concentrations. Still others, although potentially harm- ful, are probably not present in sufficient concentrations to con- tribute to the hazard, and some may be hazardous only Irhen they interact with other substances in the smoke. Substances and classes of substances in cigarette smoke lrhich have been judged to contribute to the hazard of cigarette smoking have been classified into three priority groups. Those compounds which are judged most likely to contribute to the health hazards of smoking are listed in table 1. Additional substances which probably contribute to the health hazards of smoking are listed in table 2. Those compounds which are suspected contributors to the health hazards of smoking in the concentrations in which they are present in tobacco smoke are listed in table 3. Nany other constituents of tobacco smoke are considered to be toxic under some conditions but probably do not present a health hazard in the concentrations in which they are generally found in cigarette smoke; these are not listed. This listing is not presented as final, and may be subject to modification as more information becomes availabIe.* In 1966, the Public Health Service prepared a technical report on "tar" and nicotine (60). Tobacco "tar" is the name given to the ag- gregate of particulate matter in cigarette smoke after subtracting nicotine and moisture. In that report it was stated : "It is clear that the overall risk associated with cigarette smoking increases as the average number of cigarettes con- sumed per day increases. In the studies which have reported other measures of exposure such as pack-years, degree of in- halation, and maximum level of cigarette consumption, the same type of relationship holds." Individuals may differ in their inherent susceptibility to diseases in which cigarette smoking plays a role and differ in their exposure to other factors which may increase the likelihood of these diseases. Within these groups of varying risk, the degree of exposure to ciga- rette smoke appears to be the most critical factor for the develop- ment of smoking related disease. Therefore, the general statement that the lower the dosage the lower the risk is the most useful guide available. It was also stated that: "It is possible for a cigarette to be altered in such a way that its `tar' and .nicotine content is reduced but certain other harmful effects, for example the effect of the gaseous phase, may be increased. Although this is a theoretical possibility, 626 there is no evidence that this has occurred to any serious degree." The consensus is that there is inadequate evidence to support a change in that view at the present time. In addition, it was concluded that "the preponderance of scientific evidence strongly suggests that the lower the `tar' and nicotine con- tent of cigarette smoke, the less harmful would be the effect." Sev- eral studies reported since that time have added strong support to this position. The present review is an attempt to identify those constituents of the "tar" as well as those constituents considered part of the gas phase which are most likely to contribute to the health hazards from cigarette smoking. TABLE l.-Compounds in cigarette smoke judged most likely to con- tribute to the health hazards of smoking. Campound RCiCPXlC~ Carbon Monoxide 6g4o-21,coo G (1. 10, 23.26, 29, 34, 35, 37, 42, 46. 49, 61, 63) Nicotine 20@-2,400 P (9) I "Tar" 3.000-33,000 P (9) It is recognized that the substances in cigarette smoke may inter- act so that the combined pathological effects of several substances may be quite different from the sum of their effects produced in isolation. An example of this type of interaction might be the car- cinogenic effects of tobacco "tar" as a tesult of the combined action of cancer initiating, cancer promoting, and cancer accelerating agents in producing the total effect. Such interactions theoretically could take place among substances within the gas phase, or sub- stances within the particulate phase, or between constituents of the gas phase and constituents of the particulate phase. In the absence of data which identify the interactions of cigarette smoke compo- nents, judgments concerning the action or identification of harmful substances in -cigarette smoke have, of necessity, been made pri- 627 TABLE 2.--Compounds in cigarette smoke judged as probable COR- tributors to the hcnith hazards of snzoking. Compound Acrolein Pr,mar~ phuc Conccntr*tioo in cl..s,ncatKm cigsrette amokc csu microgr~ms/ctp~rcrtc P--pnrticulate ?kfCrCnC" 45-140 G (12. 20, 21, 27, 36. 43. 45) Cresol (all isomers) 68-97 P 120. 40) Hydrocyanic Acid 100-400 G (26,38,43.45.46, 49,53) Nitric Oxide Nitrogen Dioxide Phenol C600 G (1.3, 15, 40,42,44, 57) O-10 G (1. 40, 44, 57) 9-202 P (7, 19,20, 32, 50, 52) marily on the basis of the action of the individual substances. Never- theless, experimental evaluation of modified cigarette smoke should be designed to take into account the possibility of such interaction. Until there is a better understanding of the relative importance of the interaction of the constituents of cigarette smoke in the de- velopment of the diseases associated with cigarette smoking, it will be difficult to assess the significance of the reduction or elimination of one or several of the constituents named in this report. However, it is reasonable to take the position that unless there is positive in- formation to the contrary, cigarettes in which overall "tar" and nicotine levels have been reduced present to the smoker lower con- centrations of the harmful substances in the particulate phase. If, at the same time, significant reductions are made in those gas phase constituents which also contribute to the hazards of smoking, the resulting product should be less hazardous to health.* The consensus is that a progressive and simultaneous reduction of all substances considewd likely to be involved in the he&h haz- ards of smoking should be encouraged as the most promising step available at the present time towards the development of a less haz- ardous cigarette. Primary emphasis should be given to the reduc- tion of the three substances or classes of substances named in the first table, and as a second priority to the reduction of those sub- stances or classes of substances in the second table before reducing 628 TDLE 3.--Compoun& in cigarette smoke judged as suspected con- tributors to the health hazards of smoX-ing. Comaaond Acetaldehyde ISO-1,440 Acetone Acetonitrile 140-200 Acrylonitrile l&l5 Ammonia 60330 Benzene 2J-Butadione 43-200 Butylamine 3 1 Carbon Dioxide 23,1OCL78,300 Crotononitrile 4 Dimethylamine lo-11 DDT cu.77 Endrin 0.06 Ethylamine 10-11 Formaldehyde 2c-41 Furfural 45-110 Hydrogen Sulphide 12-35 Hydroquinone 83 Methacrolein 9-11 Methyl Alcohol 90-300 Methylamine 2&22 Nickel compounds a-O.58 Pyridine 25-218 LB-650 12-100 c G G G G G G P G G P P P G G P G P G G G P P (4, 21, 27, 36, 43, 45,43,49, 53.59) (12, 21. 27, 36, 43, 45, 48. 49, 53) (12, 43) (12.43) (2, 22. 40, 41, 43, 64) (11, 12, 25, 43.45, 49, 53) (43, 46, 49, 53) (31,40,41) (1, 10.15, 23,26, 29,34,35,42,46,49, 63) (43) (31,40,41) (17, 39, 54) (14) (22,31,40,41) (4, 36, 43, 48, 53) (4,13,36) (10,43,51.58) (67) (12, 43) (12, 21, 43, 46. 49) (22,31,40,41) (5, 8, 47. 55, 56) (4% 62) those named in the third table. 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