Some biological aspects of air pollution

SOME BIOLOGICAL ASPECTS OF AIR POLLUTION Contrary to widely held opinion, air pollu- tion has been a problem for centuries. In ancient times, Roman citizens complained about smoke from dwellings, and 300 years ago this nuisance was the subject of a pam- phlet 1 addressed to King Charles 11 of England. By the twentieth century, it had become a major problem in many countries of the world. Until recently, atmospheric pollution seems to have been due mainly to the sulfur oxides, ash, and soot discharged from domestic fur- naces, industrial plants, power stations, and steam locomotives burning mineral fuel. Today air pollution control and abatement programmes have helped reduce the smoke problem, both in theory and in practice. In a number of countries, restrictions have been placed on the sulfur content in fuel, natural gas is being substituted for mineral fuels, industrial processes have been electrified, and a number of other measures-such as the provision of effluent cleaning devices-have been taken. At the same time, however, the development of every type of industry (parti- cularly chemical plants) and the chaotic growth of towns with an endless flow of motor traffic and no special industrial zones are intensifying other forms of air pollution. Over the past twenty years, air pollution has received constant attention from WHO, which has held a number of conferences and expert committees on the subject. In addition to studying adverse effects on human health (in the widest sense), these meetings have dealt with the monitoring and measurement of air pollution as prerequisites for its abatement. Dr Izmerov is Assistant Director-General, World Health Organization. by N. F. Izmerov WHO encourages epidemiological surveys in countries with differing air pollution prob- lems and assists them in formulating prac- tical control measures and legislation on the subject and, in general, in providing guidance on any abatement or preventivl:l measures they may wish to take. It also supports the train- ing of staff at all levels for the prevention and control of air pollution. During the past few years, the Organization has promoted the creation of international and regional reference centres for the sys- tematic collection and dissemination of data on the results of air pollution investigations and the efficacy of control measures. Some instances of air pollution Several classic examples of the health effects of acute exposure to air pollutants have been recorded. During the " pea-soup " fogs in London in 1873, 1880, 1882, 1891, and 1902, increases in the death rate were noted. Toxic fogs have occurred in London in more recent times-in 1948, 1952, 1956, 1959, and 1962-again increasing mortality among par- ticularly susceptible groups. A study of overall mortality in New York in 1962-64 showed five recurring mortality peaks following periods of intense atmos- pheric pollution and temperature inversion. Increases in morbidity as a result of fogs following periods of temperature inversion and industrial pollution of the air also oc- curred in the Meuse valley in Belgium in 1930, in Donora (USA) in 1948, and in Poza Rica (Mexico) in 1950. The urgent need to fight for clean air is clearly indicated by the increase in chronic disease of the upper respiratory tract, particularly bronchitis and emphysema, 51 and in allergic diseases, such as asthma, that has been noted in recent years in a number of countries. Epidemics of " asthma " in New Orleans and in the Tokyo-Yokohama region have undoubtedly been related to air pollu- tion. There are indications that atmospheric pollution may be a contributory factor in human lung cancer. Epidemiological data indicate a constant rise in the frequency of lung cancer in towns as compared with the country, and this cannot be entirely explained by differences in the prevalence of the smok- ing habit. Mention should also be made ofthe period- ic " smogs " caused in Los Angeles by photo- chemical reaction between hydrocarbons and oxides of nitrogen discharged in the exhaust gases from motor traffic and leading to irritation of the mucous of the ears, nose, and throat. Smogs of this kind have also been observed in San Francisco, Washington, D.C., and New York. The worldwide growth of motor transport has been accompanied by similar phenomena in countries such as Aus- tralia, Italy, and Japan. At Moscow, Baku, and Batum in the USSR, pilot studies have demonstrated the presence in the air during the summer, when solar radiation is intense, of oxidants produced by photochemical trans- formations of motor exhaust gases. In addi- tion to irritating the eyes and the upper res- piratory tract, photochemical smog has a profound effect on lung function, particularly in people suffering from chronic respiratory diseases. Genetic effects of pollution In 1963 a WHO Expert Committee on Human Genetics 2 emphasized the possibility of an increase in the frequency of mutations through the action of such environmental factors as ionizing radiation and chemical mutagens. Ionizing radiation is known to cause mutations in all organisms, and man is no exception. A large number of the most varied chemical substances and compounds have also been found to have genetic effects. Every year hundreds of new organic com- pounds are synthesized in various countries of the world. Many of them, such as pesti- 52 cides, defoliants, plastics, detergents, and drugs, are widely used, but few of them have been studied from a toxicological and phy- siological standpoint. Few facts are available on the transformations that these substances may undergo in the air, on their combined effects, or on their possible carcinogenic and teratogenic properties. The basis for legislation Atmospheric pollution is becoming a real hazard not only to human health but also to the health of plants and animals; in addition, it reduces visibility in towns and corrodes and spoils buildings and monuments. For effec- tive control that will not only interrupt pollu- tion but prevent further pollution, a legal basis is needed. On what should legislation for pollution control be based? What requirements should be laid down in regard to sources of pollu- tion? To what degree should industrial effiu- ents be purified to prevent pollution of the atmosphere? The answers to these and many other questions with a bearing on legislation depend primarily on the effect on man of various concentrations of substances dis- charged into the atmosphere. Should absolutely pure air be insisted upon? In other words, should the air have the same composition as it would have in an environ- ment uncontaminated by man? Not neces- sarily, since there are no grounds for asserting that every deviation from the natural com- position of the air will have an unfavourable effect. It is well known that a number of potentially toxic chemicals and compounds are normally found in human tissues or are formed by human metabolism. Examples are arsenic, mercury, and lead. There is no evi- dence to disprove the assertion of Lazarev 3 that for each toxicant (with the possible exception of chemical mutagens) there is a threshold of effective concentrations and doses below which no harmful effect will be ob- served. In the WHO monograph Air Pollution, Heimann 4 pointed out that to maintain health it is not at all necessary that the air we breathe should contain no impurities what- soever. What is important is not so much the presence of impurities as their concen- trations. We must know what levels of pollu- tants in the atmosphere are dangerous. It has been said that, at the present level of technical development, it is practi- cally impossible to eliminate toxic concen- trations of certain pollutants from the atmo- sphere, but there are, in fact, few questions connected with the technology of atmospheric pollution control that have not been solved from the theoretical and indeed the practical point of view. In 1963 a WHO Expert Committee on Atmospheric Pollutants 5 approved the basic conclusions of a WHO Inter-Regional Symposium on Criteria for Air Quality and Methods of Measurement and suggested, as guides to air quality, four categories of concentrations, exposure times, and corres- ponding effects: Level I. Concentrations and exposure times at or below which, according to present knowledge, neither direct nor indirect effects (including alteration of reflexes or of adaptive or protective reactions) have been observed. Level Il. Concentrations and exposure times at and above which there is likely to be irritation of the sensory organs, harmful effects on vegetation, visibility reduction, or other adverse effects on the environment. Level Ill. Concentrations and exposure times at and above which there is likely to be impairment of vital physiological functions or changes that may lead to chronic diseases or shortening of life. Level IV. Concentrations and exposure times at and above which there is likely to be acute illness or death in susceptible groups of the population. Level I is of primary practical interest for the control of atmospheric pollution, since no concentrations above that level should be permitted. Adaptation In considering the harmful effects of atmos- pheric pollution, it is essential to make a correct assessment of the significance of adap- tation. A WHO Expert Committee on Envi- ronmental Change and Resulting Impacts on Health,6 which met in 1964, noted that man's capacity for adaptation is quite high and therefore that the pessimistic forecasts often made are hardly justified. It is difficult to argue with that conclusion but, as Davy- dovski 7 has pointed out, adaptation to the environment is often purchased at the price of considerable morphological and functional changes. The same observation has been made by Rene Dubos, 8 who considers that adaptation to external conditions at any given moment will affect human well-being in the future and have social consequences. Studies of the morphological changes occur- ring in the internal organs in the course of adaptation to high altitudes 9 have revealed dystrophic manifestations in the heart, lead- ing to fragmentation and segmentation. In the lungs sloughing of the alveolar epithelium was found, with small foci of atelectasis and emphysema. Liver cells showed cloudy swelling and were often vacuolated, while in the kidneys there was degeneration and necro- sis of the convoluted tubules. It is also known that adaptation to irritant gases takes the form of a catarrhal condition of the mucosa of the upper respiratory tract which causes the sense of irritation to disap- pear. This does not mean that the irritant gases do not continue to have a harmful effect on the deeper parts of the respiratory tract. Adaptation as a result of chronic expo- sure to toxic substances is of an obviously pathological nature. It must be borne in mind first of all that air pollutants have a biological effect and that the determination of harmless concentrations involves the bio- logical problem of the physiological boun- daries of the organism's adaptation to the environment. Pavlov 10 wrote that, from a biological point of view, the functional activity of living organisms is a result of many centuries of adaptation to the environment and the hered- itary transmission of acquired morphological and physiological properties. In the course of phytogenesis, the organism has established specific and non-specific adaptive mechanisms of many different kinds. The specific mecha- 53 nisms are mainly designed to deal with envi- ronmental conditions that change rapidly, such as heat and cold, light and dark. They comprise the fine adaptive reactions of the heat regulation system, the adaptive mecha- nisms of the eye, etc. Among the mechanisms triggering off these reactions are the body's exteroceptors and interoceptors, which are constantly on guard, reacting sensitively to changing environmental conditions and trans- mitting signals to various parts of the central nervous system, which controls the adaptive reactions. However, the body may be exposed to the harmful effect of chemical irritants to an extent which, because it exceeds the capa- cities of the physiological protective mecha- nisms, requires the mobilization of defensive reserves whose role is to compensate for the disturbed functions. According to Stern,U individual organisms, including human beings, survive in polluted air because they possess physiological reserves. Any policy that in- volves accepting pollution as long as no damage to man and his environment is ap- parent is one of" brinkmanship ". It is thus extremely important to determine the boundary between physiological adaptation, which does not involve stress, and pathological reactions requiring compensation of disturbed function in order to maintain normal interrelation- ships between the organism and the environ- ment. For this purpose, the biological effects and hygienic significance of atmospheric pol- lutants must be defined with the aid of a variety of scientists-physicians, physicists, chemists, toxicologists, etc. It is impossible to accept concentrations of atmospheric pol- lutants at and above which there is likely to be irritation of the sensory organs, for such irritation can only be dangerous. Physiological reactions to pollutants The local effect of any irritant cannot be divorced from the general reflex effect, in which the organism is involved as a whole. The significance of this general reflex effect is seen with particular clarity in the case of exposure to small concentrations of chemical substances that do not directly cause gross 54 disturbances but may influence receptors and induce various reflexes. According to Pavlov:12 The animal organism as a system exists in the natural environment only by constantly bringing itself into balance with that environment, i.e., by means of definite reactions of the living system to the stimuli acting on it from outside. In the higher animals this is mainly done through the nervous system in the form of reflexes. Consequently, careful study is needed of the effect of small concentrations of poten- tially harmful substances that influence the reflex mechanisms ensuring the functioning of the body as a whole. The body surfaces that come into contact with environmental factors-the skin, the gastrointestinal tract, and the respiratory tract-are copiously supplied with sensitive receptors and act as zones in which reflexes are initiated affecting all the bodily functions without exception. They are therefore of particular concern. The surface of the respiratory tract is of most interest in that it is a reflexogenic zone acted upon by all the impurities occurring in the atmosphere. The olfactory receptors are highly sensitive to chemical substances. Man can often detect by smell the presence in the atmosphere of concentrations of some substances too small to be detected by any chemical method. Reflexes triggered off by the olfactory receptors can affect the condi- tion of the whole body. Experiments have shown that the inhalation of insignificant concentrations of highly odorous substances may cause changes in gas exchange in animals; reflexes from the olfactory nerve may change their whole rhythm of respiration. Stimu- lation of the olfactory receptors by various odorous substances brings about changes in the pulsation of the cerebral vessels and increases intracranial pressure, as has been convincingly proved by Nadzarjan.H Bari 14 demonstrated that, when the olfac- tory organ was stimulated with odorous sub- stances, changes occurred in the electrical acti- vity of the cerebral cortex as shown by a depression of the rhythms on electroencepha- lograms, the alpha waves either decreasing or disappearing. Consequently, odours and the reflexes they cause are not without importance for the organism. The body's reaction to chemical substances in the air is not limited merely to reflexes initiated by the olfactory receptors. When polluted air is inhaled, all parts of the respiratory tract are inevitably subjected to irritation, protective reactions of the respiratory organs and also of the heart immediately occur, and the whole system of adaptation to environmental conditions comes into play. Stimulation of the receptors of the olfactory analyser brings about excitation in the cere- bral cortex, and this in turn involves the organs of sight, the heart, etc. Olfactory stimuli affect the sensitivity of the eyes to light. Studies of the effect of various odours on the functional condition of the visual analyser, with a view to setting standards for maximum permissible concen- trations in the atmosphere, have been carried out by a number of Soviet hygienists, includ- ing Bustueva 15 and others, who noted that some substances brought about changes in the dark adaptation curve at concentrations not perceptible to the sense of smell. For example, the olfactory threshold for furfural is 1.0 mg/m3 and the threshold of effect on sensitivity to light is 0.3 mg/m3 • To be acceptable, concentrations of pollu- tants in air must be not only below the thresh- old of smell, but also below the threshold at which reflex reactions occur that may change the condition of the cerebral cortex. It should be noted that benzine, formaldehyde, chlor- ine, and other substances affect light sensi- tivity only in concentrations considerably above those perceptible by smell. For a long time the adaptometric method remained the most responsive and sensitive technique used by Soviet research workers in detecting reactions in the receptors of the nasal cavity and the upper respiratory tract that affect the functional condition of the cerebral cortex. In 1959, Bustueva et al,16 used the electroencephalographic method in various forms and this proved still more sensi- tive than adaptometry. For example, with the light sensitivity method, the action thresh- old for furfural was found to be 0.3 mg/m3, but when the technique of the electrocortical conditioned reflex was used the threshold was 0.08 mg/m3• The corresponding figures for methyl acetate ware 0.18 and 0.08 mg/m3, and for styrene 0.02 and 0.005 mg/m3 respectively. Electroencephalography and measurements of the olfactory threshold and the light sensi- tivity of the eye are suitable for studying the short-term biological effects of atmospheric pollutants. They make it possible to deter- mine the concentration at which the pollu- tants in the atmosphere begin to exert a bio- logical effect on the organism. However, a large variety of atmospheric pollutants-for example, lead, mercury, dust, and carcino- gens-are capable of causing only long-term effects. Animal experiments The literature contains a great deal of information on morbidity connected with atmospheric pollution. However, in morbi- dity studies, even when it is known that atmos- pheric pollution in the areas concerned is high, it is difficult to state with certainty that the polluted air is the sole cause of the ill- nesses recorded. Even in cases where evi- dence on the effects of high concentrations is available, it is difficult to determine the level of pollution that will not disturb comfort. Animal experiments help, to a considerable degree, to determine the long-term biological effects of atmospheric pollutants. The conditioned-reflex method is being suc- cessfully used in the USSR, for detecting early effects on the animal organism of small concentrations of atmospheric pollutants. This method makes it possible not only to determine the threshold concentration of a substance and its zone of toxicity, but also to establish the nature of changes in the reac- tivity of the cerebral cortex and to detect the possibility of chronic poisoning when the organism is exposed to the toxic substance over a long period. As long ago as 1908, Russian scientists were investigating the use of the conditioned-reflex method in pharma- cology. In this connexion, Pavlov wrote :17 By using small doses of different toxins, we failed to produce any visible abnormalities in the motor 55 system of the animals. They remained outwardly quite normal. The conditioned-reflex method, how- ever, showed that there was a difference: for example, conditioned reflexes disappeared. Other experiments showed that the condi- tioned-reflex method is the subtlest indicator of the effect of toxins on the complex nervous functions of the central nervous system. In 1938 the method was adopted in industrial toxicology in the USSR; the techniques have of course changed with time. In 1949-50 Kotljarevskij 18 proposed a method for studying motor- and food-condi- tioned reflexes in laboratory animals. This method is now being widely used not only in the USSR but elsewhere to study the effect of toxic substances on higher nervous activity. Novikov 19 established that the chronic exposure of white rats (six hours a day for five-and-a-half-months) to benzene in a con- centration of 64 mg/m3 caused changes in conditioned-reflex activity. These took the form of disinhibition of differentiation, alte- rations in the latent periods of the conditioned reflexes, the disappearance of such reflexes, and the appearance of equalizing and para- doxical phases. It should be noted that these changes did not occur immediately but only after two to four months of exposure. They were most marked towards the end of the experiment. The disturbances were of a func- tional nature, and once exposure had ceased function returned to normal within a month. No substantial changes in the composition of the blood were noted, nor were there any external changes in the animals, They devel- oped normally and gained weight. This and other research 20 into the conditioned-reflex activity of animals has made it possible to determine the concentrations of atmospheric pollutants that induce functional changes, i.e., that cause the body to mobilize its pro- tective mechanisms to prevent a pathological condition from arising. Evidence of the appearance of protective and adaptive reac- tions in animals following experimental long- term exposure to atmospheric pollutants is also furnished by the excretion of copropor- phyrin in the urine, changes in the degree of dispersion of the serum proteins, etc. 56 Indirect effects on man In addition to their direct effects on man, allowance must also be made for the indirect effects of atmospheric pollutants, such as the reduction of the transparency of the atmos- phere, the contamination of vegetation, fruit, vegetables, etc.-in short, their action on a variety of things influencing man's feeling of well-being. The only level of air pollution that can be permitted is one that has no direct or indirect effect on human health. This approach is not utopian, but in full agreement with the well-known definition in the Con- stitution of the World Health Organization: " Health is a state of complete physical, mental and social well-being and not merely the absence of disease and infirmity." The attainment of the highest possible level of health is the aim of all the peoples of the world, and scientists everywhere must unite their efforts not only to clean up the atmos- phere, but to prevent it being contaminated again in the future. REFERENCES 1 Evelyn, J. (1961) Fumifugium (reprinted 1968, London, National Smoke Abatement Society) 1 WHO Expert Committee on Human Genetics (1964) Human genetics and public health : Second report of the ... , Geneva (Wid Hlth Org. techn. Rep. Ser., No. 282) 1 Lazarev, N. V. (1938) [Elements of industrial toxico- logy], Moscow, Medgiz • Heimann, H. (1961) Effects of air pollution on human health. In: Air pollution, Geneva (World Health Organization: Monograph Series, No. 46), pp. 159-220 • WHO Expert Committee on Atmospheric Pollutants (1964) Report, Geneva (Wld Hlth Org. techn. Rep. Ser., No. 271) • WHO Expert Committee on Environmental Change and Resulting Impacts on Health (1964) Report, Geneva (Wid Hlth Org. techn. Rep. Ser., No. 292) 7 Davydovski, I. V. (1958) [Pathological anatomy], Moscow, Medgiz • Dubos, R. (1965) Man adapting, New Haven, Yale University Press • Rahimov, Ja. & Etinger, L. (1969) [The morphology of the internal organs under high-mountain conditions], Dusambe 10 Pavlov, I. P. (1940) [Collected works], vol. 1, Moscow, Medgiz, p. 387 " Stern, A. C. (1965) Basis for criteria and standards, J. Air Pollut. Control Ass., 15, 281 12 Pavlov, I. P. (1940) [Collected works], vol. 3, Moscow, Medgiz, p. 560 17 Pavlov, I. P. (1951) [Twenty years' experience of objective study of the higher nervous activity in animals], 7th ed., Moscow, Medgiz, p. 213 " Nadzarjan, N. A. (1948) [The effect of stimulation of the auditory, olfactory, and visual exteroceptor systems on the work of the craniocerebral vessels], Vestn. Oto-rino-laring., 1, 37 11 Kotljarevskij, L. I. (1951) [Methods of studying conditioned motor reflexes in certain small animals (squirrels, rats, and guinea-pigs)] :t. vys§. nerv. Dejat. Pavlova, 2, 5 " Bari, F. A. (1952) [Changes in the electrical activity of the cortex of the cerebral hemispheres upon stimula- tion of the olfactory organs], Vop. Nejrokhir, 16, No. 3, 47 11 Novikov, Ju. V. (1958) [Background information for establishing the maximum permissible concentration of benzene in the ambient air]. In: Rjazanov, V. A., ed. [Maximum permissible concentrations of atmos- pheric pollution], No. 3, Moscow, Medgiz, p. 85 " Bustueva, K. A. (1957) [The toxicity of sulfuric acid aerosol], Gig. i Sanit., 22, No. 2, 17 " Bustueva, K. A., Polezaev, E. F. & Semenenko, A. D. (1960) [The effects of subliminal olfactory stimuli on reflex activity], Fiziol. :t. (Mask.), 46, 452 •• Izmerov, N. F. (1961) [Pollution of the atmosphere with benzene fumes and the maximum permissible concentration of benzene]. In: Rjazanov, V. A., ed. [Maximum permissible concentrations of atmospheric pollution], No. 5. Moscow, Medgiz, p. 72 Treating drug dependence by antagonists The use of specific antagonists to drugs of the morphine type is a relatively recent development in the treatment of persons dependent on such drugs. These antagonists will precipitate abstinence phenomena when given to such dependent persons. On the other hand, when given to patients who have no physical dependence on morphine-like drugs, they tend to block the acute effects that otherwise would result from the admin- istration of drugs of this type. If antagonists are administered regularly, they help to prevent the development of dependence and reduce the chance of a fatal overdose, should the patient attempt to use such drugs. Cyclazocine, a specific opiate antagonist, has been subjected to clinical trials with individuals dependent on heroin. It is effective orally but may produce some unpleasant subjective side-effects and its antagonistic action lasts only about 24 hours. Consequently, if a patient omits only one dose he may experience major effects from drugs of the morphine type. Naloxone, another specific opiate antagonist, is free of subjective side-effects, but financially prohibitive amounts are necessary to produce effective antagonistic effects by the oral route and its duration of action is rather less than 24 hours. Work is at present proceeding on the development of a form of these drugs suitable for implantation so that a single administration will be effective for several weeks. The number of subjects treated by these drugs is small and none of the published studies has included adequate assessment of control groups. They are much more dif- ficult to use than methadone and less appealing to patients. As noted, narcotics must first be withdrawn from the patient, a process which many persons dependent on heroin are not eager to undergo, and the associated desire for narcotics may not be completely suppressed. Nevertheless, the use of antagonists has a number of potential advantages. Since they do not produce dependence of the morphine type, they can be given to persons who are experimenting with such drugs, but who have not yet become dependent. This may help to prevent the further development of such experimentation. Further, the antagonists can readily be withdrawn without causing drug-seeking behaviour. Such withdrawal may be undertaken when it is determined that there is little probability that the patient (whether a former casual or regular user) will resume his pattern of drug use. The patient would thus be freed of the necessity to take any drug. From: WHO Expert Committee on Drug Depend- ence (1970) Eighteenth Report, Geneva (Wld Hlth Org. techn. Rep. Ser., No. 460), p. 25. 57