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Aril. hig. rada toksikol., 37 (1986) 253--274. Review UDC 613.633:549.6 DISEASES ASSOCIATED WITH THE INHALATION OF ASBESTOS DUST C. N, Davies Pilcox Hail, Tendring, Essex, United Kingdom i (Received for publication February 10, 1986) C. ,'w Ij* Examination of publications about asbestosis shows that the disease is caused by breathing asbestos fibres longer than 10-- 15 m. Shorter fibres are cleared from the lungs by phagocytes. Sort chrysotile is much more ^active in the lung in causing asbe stosis than any other varieties of asbestos. The relevance of the alleged,higher solubility of chrysotile, compared with other varie ties of asbestos is uncertain because it is not toxic ;to phago- 1 cytes and the fibres can be extremely fine and difficult td detect, even with a good transmission electron microscope. Solution may result in fragmentation of fibres into short lengths rather than reduction in diameter. Lung carcinoma is also caused by long soft fibres of chrysotile and is peribronchiolar in origin because the curled, splayed fi bres do not work their way through the lungs with the aid of the cyclic respiratory movements. Hard, needle shaped, smooth fibres of the amphiboles travel through the lung tissue and, if long enough to escape phagocytosis, cause carcinoma. Mesothelioma of the pleura is caused by tong inhaled fibres of amiphibole which have travelled from the airways to the pleura. It can be caused by direct injection or application to the pleura of animals of chrysotile asbestos fibres of any length but does not result from inhalation because the curled, splayed fibres of soft chrysotile anchor themselves in lung tissue and do not travel to the pleura. Selective sampling of airborne asbestos dust is necessary to pick out the small proportion of disease-causing fibres from the considerable amount of short fibre dust which is disposed of by phagocytes before it can do any harm. A selective sampler must sample and retain fibres longer than 10--15 pm, and with diameters An the range 0.1--0.5 pm. It is useless to select on the basis of aerodynamic diameter beoause such a criterion is insensitive to the length of fibre. Some recent selective sampling systems are described. Invited paper written on the'occasion of the 35th Anniversary of the In stitute for Medical Research and Occupational Health in Zagreb when the author was awarded a plaque and a testimonial in recognition of long stand ing scientific collaboration and assistance. 253 HWBUI0001874 Davies, C. N.: Diseases Associated with the Inhalation of Asbestos Dust. Arh. hig. tafia tokslkol., Vol. 37 (1986) No. 2, pp. 253--274. 1. INTRODUCTION There as still some uncertainty about the reasons why breathing asbestos may result in three different diseases;, asbestosis, lung carci noma and mesothelioma. The following review of ^h'e last fifty years' experimental work on animals and observations of .persons who have breathed asbestos dust, shows that the differentiation of the three di seases can be accounted for, although some of the experiments could have given more help in this direction had .they .been planned intuitively rather .than statistically. The early realisation of the importance of long fibres failed to prevent lhe use of gravimetric sampling methods which persisted into the 1970's; they are useless as an' index of health risk (11 and have now been replaced by the method of counting fibres on membrane filter samp les which is sound but tedious (2). Asbestos fibres can be too fine for detection by optical microscopy. Use of scanning electron microscopy on membrane filter samples has been described by Spumy and co-workers (3) who employed electron microprobe analysis for the identification of the varieties of asbestos and other fibres. The next development, aimed at .speeding up the evaluation of samp- les, is for selective sampling on a basis of fibre length. When this has been achieved, gravimetric assessment should .be possible. Moves in this direction are described in the penultimate section of this .paper. Advances in the understanding of asbestos diseases come mainly from experimental studies of lung residues. Techniques of digestion of tissue for the recovery of inhaled, deposited and retained dust have been dis cussed by Weller (4), . i.f,.'. - . . VI*'2.'ASBESTOS: DISEASES AND HEALTH STANDARDS " ' Asbestos minerals have bean exploited on an industrial scale since 1878. Fibrosis of the lungs caused by inhaling asbestos dust was first recognized in 1900 and named asbestosis about 1927. Association of the airborne dust with lung cancer dates from 1934 and was demonstrated statistically by Doll in 1955 (5); mesothelioma was related to asbestos about 1950 (6, 7). In 1930, asbestosis was recognised as a compemsatable industrial disease. In 1968 Hygiene Standards for Chrysotile Asbestos Dust were published by the British Occupational Hygiene Society (8); they were based On a study of asbestosis due to industrial exposures and calculated on a 1% chance of a person contracting asbestosis after am accumulated exposure of 100 fibre years per cm* of air, the fibres being over 5 pm in length, diameter not being stated. Ignorance of arny quanti tative relationship between exposure to asbestos dust and risk'of cancer of the lung or of mesothelioma made it impossible to specify standards of exposure for these diseases. 254 Davies, C. N.: Diseases Associated with the Inhalation of'Asbestos Dust. Arh. hig. rada toksilxo!., VoJ. 37 C1986) No. 2, pp 253--274. In 1970, New Asbestos Regulations were imposed in the U. K., which amounted to fixing the permitted airborne concentration at not more than 2 fibres per am3, a fibre being 5 p.m or more in length and having a ratio of length to diameter of at least 3 : 1 (9). This concentration was halved in the Final Report of the Advisory Committee on Asbestos (10). Their own 1968 Standards were endorsed by the British Occupational Hygiene Society (BOHS) (11) and a similar Standard for Amositc As bestos was published at the same time. In 1983 the BOHS studied phy siological effects associated with asbestosis in more than 600 persons who had been exposed in factories for over 10 years (12). As a result, for fibres exceeding 5 pm in length, the 1968 airborne level of 100 fibre years/cm3 was reckoned to produce 17 to 20% recognizable occurrence of adverse effects, rather than the 1% chance of asbestosis given in 1968. For 25 fibre years/cm3 the chance of adverse effects was now 2% and for 50 fibre years/cms, 7%. Directives of the European Communities followed in 1983 and 1984 which were discussed by Stellingwerf (13). 3. FIBRE LENGTH AND ASBESTOSIS The fact that only fibres above a certain length would cause asbesto sis. was established by L. U. Gardner at Saranac by his classical series of animal experiments with chrysotile and other types of asbestos. He worked through the I930's but published little; his results were review ed after his death in 1946 by Vorwald and co-workers (14). They con cluded that some species of animal, on exposure to asbestos fibres from 20 to 50 pm in length, developed peribronchiolar fibrosis of the lung similar to human asbestosis. Shorter fibres did not provoke this reac tion; the upper- limit of length was not determined, but would depend on the inhalability of fibres longer than 50 pm. It was also concluded that the formation of asbestos bodies in the lung was due to the coating of fibres by blood and tissue elements, which resulted in loss of ability of the fibres to produce fibrosis. These conclusions were challenged by Beattie and Knox (15) and Beattie (16), who examined small parts of the lungs of men who had worked with asbestos; they failed to relate the severity of asbestos lesions to the mineral content of dried lung, probably .because they were unable to ascertain the weight of mineral in the fresh whole lung. They pro posed a theory of tire formation of asbestos bodies on fibres and the subsequent disintegration of the bodies with release of a fibrogenic agent; this theory is unattractive because asbestos bodies are rare in subjects exposed to chrysotile which represented about 92% of the European industrial consumption of asbestos (17) and there is no cor relation between the number of asbestos bodies found in sputum and the severity of asbestosis (18); also, asbestos bodies are rarely found in rats with asbestosis which has resulted from inhalation (19). 255 HWBUI0001875 Davies, 0. N.: Diseases Associated with the Inhalation of Asbestos Dust. Arh. hig. rada toksikol., Vol. 37 (1986) No. 2, pp. 253--274. It is fairly obvious that long fibres are dangerous 'because (phagocytes are unable to transport them (6, 20). Short fibres accumulate in the lymphatic system, where they cause only mild fibrosis (21). Conning and co-workers (22) show a correlation -between the produc tion of asbestosis in rats and the cytotoxicity in vitro of the same dust to cultured macrophages from similar rats. The chrysotile asbestos con sisted of fibres from 1--3 jum diameter and 0.5--200 jtm long; unfortu nately the dead cells were not examined so their mortality was not correlated with length of fibre. The toxic action of fibres of asbestos short enough to be engorged by macrophages is very much less than that of quartz particles; chrysotile is the most soluble variety of asbestos (not in alkali). Evidence of the handling by phagocytes of asbestos of several types, with fibres all shorter than 10 is provided by the inhalation experi ments with rats which were carried out by Morgan and co-workers (23). Fifteen to twenty percent of the fibres inhaled were deposited in the lower respiratory tract with total depositions of 30% to 75/o. The fibre median diameters were from 0.15 /cm to 0.46 /im. Of the initial deposits only about 5% remained 120 days after inhalation of the dust, either because they had been removed with the aid of phagocytes or had dis solved. These observations are paralleled by the intrapleural injection experi ments in rats by Monchanx and co-workers (24) using fibres of'chryso tile and crocidolite, over 90% being below 10 ;<m an length. Ninety days after injection fibres were recovered from the lung parenchyma and the mediastinal lymph nodes. The chrysotile migrated less readily and pro duced a greater inflammatory reaction than crocidolite, each of these factors suggesting a connection with the characteristic form of soft chrysotile. -!. `' '1 The amount of asbestos in the lungs should correlate with the amount of airborne dust. This is so for amphiboles but less chrysotile has often been found, indicating less deposition or more elimination (25). Chryso tile is the most soluble variety of asbestos and loss in this way has been given as the reason for its short lifetime in much published work. Long fibres, which become coated while in the lung and turn into asbestos bodies, sometimes appear to break into short lengths. The inability of the lung to free itself of long fibres is commented on by Timbrell (26) who compared the distributions by diameter and by length of particles of anthophylldte asbestos, in the air of a mine in Finland, with particles recovered .from the lungs of decreased em ployees of the mine. He believes that his data indicate complete clearance of short fibres with clearance decreasing as length increases, the reten tion becoming complete at about 14 /im (length since the phagocytes cannot handle fibres which are greater than themselves. There is ample evidence of the ability of occasional fine fibres as long as 100 /an to reach the finest airways of the human lungs (15, 27); 256 Davies, C. N.: Diseases Associated with the Inhalation of Asbestos Dust. Arh. hig. rada toksikol., Vol. 37 (1986) No. 2, pp. 253-274. this is because of the tendency of fibres to align themselves along the flow direction, and to stay aligned if they drift to the axis of an airway, coupled with their very small Stokes' number, that is the ratio of the fibre stop-distance to airway diameter. The stop-distance is a measure of the tendency of (the mass of a partible to (keep it moving in the same direction whilst the fluid drag of the air, which carries it along, tends to hold it in the air stream when this changes direction. Small Stokes' number means that fibres oriented along the flow lines follow their course and do not often make contact with the walls of the airways. Wagner and co-workers (25) present distributions of the fibre content of lung samples from men who had sought compensation for asbestosis. The median lung loading for chrysotile was only about 5.10" fibres/g tissue for all grades of severity of asbestosis. For the amphiboles some 40 times as many fibres were required for grade 3 asbestosis, the most severe. Ten times as many fibres were needed for grade 2 and only 0.2 times for grade 1. These ratios hint at a long term chemical activity in chrysotile. A comparison of the effects of fibres of glass, chrysotile and of crocidolite asbestos is reported by Pickrell and co-workers (28). They were administered to hamsters by intratracheal instillation, doses ranging from 2 to 21 mg, of which 0.01 to 6.2 mg (2 x 10s to over 10' fibres) had aerodynamic diameters below 5 /om. Lengths of the fibres are not given. One of the glass fibre samples (microfibre 2) had a bimodal distribu tion of diameter, 2/3 of the count had a mode at 0.1 to 0.2 /cm and 1/3 at 1 to 1.3 /cm; these fibres were of glass without binder. This sample of glass fibre produced more appreciable biological effects than othor. coarser samples. The cytotoxicity to pulmonary alveolar macrophages was less than that of crocidolite but more than chrysotile. Like asbes tos, instillation of microfibre 2 increased collagen in lung tissue, the maxi mal response being at 11 months. These observations indicate similar reactions to fine glass fibres and to asbestos. The different chemical natures of these substances suggests that their common reaction is due to their fibrous form. 4. FIBRE LENGTH, LUNG TUMOURS AND MESOTHELIOMA Wagner and co-workers (19) exposed rats to airborne dusts of UICC standard reference samples of fine varieties of asbestos 'for periods up to 24 months. The characteristics of the fibres of these dusts have been described by Timbrell (29) and Harris and Timbrell (30). Mean mass respirable dust concentrations were measured in the exposure chamber by a selective gravimetric sampler which took small account of partic les settling at more than 0.08 cm/sec (aerodynamic diameter 5 /cm). The respirable dust concentrations ranged from 10--14 mg/m3. Each kind of asbestos produced asbestosis and lung tumours. The weight of dust 257 HWBUI0001876 Davies, C. Nlr Diseases Associated with the Inhalation of Asbestos Dust, Ath. lilg. rada toksikol., Vol. 37 (1986) No. 2, pp. 253-274. iil the lungs of animals breathing the amphiboles (amosite, anthophyllite and crocidolite) increased steadily during exposure up to'24 months. The weight'off chrysotile found in the lungs Of animals breathing this variety of asbestos dust for 24 months was only dbdut 1/30, of that in the' ampbibole-breathing animals and did not change much after the first three months. The severity of asbestosis was much the same, irre spective of'which dust had been breathed, and increased more or less steadily'`with the length of exposure. Lung tumours appeared after 10 months, when asbestosis was moderate. Mesotheliomas appeared in animals breathing the amphiboles and Canadian chrysotile but not with Rhodesian chrysotile; their appearance did not correlate with length of exposure. f Mesothelipmas' have also been produced by the intrapleural injection into rats of 20 mg of fine fibred* chrysotile (31).' In this paper further inhalation experiments are also described in whith aerosols'of chryso lite having 500 fibres/cm3 longer than 5 pm (10.8 mg/m3 respirable dust) were breathed by rats for up to 12 months. Moderate asbestosis, some lung tu-moursbut no mesotheliomas, were recorded. Bolton and co-workers (32) employed lintraperitoneal injection of rats to assess the relative tendencies to produce mesotheliomas of fine chrysotiles and two amosites. The particles were collected by filtration from airborne dusts, 40/n being longer than 2--3 /tm and 2% longer than 12--20 pm. No distributions of fibre diameters are given but all were less than one third of the length. The chiysotiles were more ag gressive than the amosites apart from a sample of chrysotile which had been heated to 850 C, There was little difference in fibre length be tween the varieties so these results fail to confirm the association of length w(ith carcinogenicity by Stanton and Wrench (33). V, Gilson 11) .reviewed human exposures, resulting in lung carcinoma which., indicated that, the risk was lowest for chrysolite and was dose- -related. He pointed out that asbestos .is an absorptive,material which may pick up hydrocarbons; smoking increases the risk of lung cancer in asbestos workers (34). This effect, however, is not specific to asbes tos; uranium miners who contract cancer due to ^-radiation also have an enhanced risk ,Jf they smoke.. Mesotheliomas were rarely associated with exposure to chrysotile or anthaphiUite; crocidolite and amosite could cause mesothelioma. There are reports of this disease occurring in persons with no known exposure to asbestos. Stumphius and Meyer (35) acoept that there is a connection between asbestos and mesotheli oma but state that cases have occurred when exposure to asbestos could not be proved..... 1 A survey of lung samples from chrysotile workers (36) showed that the ratio of'tremolite to chrysotile in the lungs was 'much greater than in the inhaled-dust, indicating either less deposition or more elimina tion of chrysotile. It is really essential for the understanding of such . 258 i Davies, C. N,: Diseases Associated with -the Inhalation of Asbestos Dust. Arh. hig, rada toksikol., Vol. 37 (1986) No. 2, pp. 253-274. observations that size analyses of fibre,,, lengths should be presented. For example a great deal of short fibre (< 10 pm) chrysotile could have been eliminated -from the lungs by phagocytosis or solution leaving signi ficant tong fibres in the lungs. It j>s inadequate to define fibres, as in this paper, by an aspect ratio of 3 : 1 or greater. In a study of lung tissue from cases of mesothelioma McDonald and co-workers (37) also used this aspect ratio as a criterion. In the case of chrysotile workers no association of lung dust with -mesothelioma was detected. For subjects with amosite and crocidolite asbestos there were correlations with mesothelioma which can be regarded as well establi shed; however, there are other causes of mesothelioma which have nothing to do with asbestos. Kannerstein and Churg (38), in a review -of -mesothelioma in man and experimental animals, emphasize the similar morphology of the disease in each species; they consider it probable that the physical form, but neither the chemical constitution -nor the molecular structure of the fibres, is responsible for the lumorigenic effect on the serous membra nes, They refer to contradictory findings regarding length of fibres, especially those below 10 pm, but fail to identify an important reason for this. Most animal mesotheliomas of the -pleura have been induced by direct application of asbestos to the pleura, a procedure which gua rantees the access of fibres of all lengths. When dust is inhaled the fibres can only reach the pleura -by their mobility in moving lung tissue and by their escaping phagocytosis; two processes which depend on fibre form and -length. 5, FIBRE DIAMETER AND ASPECT RATIO Asbestos fibres cleave longitudinally down to diameters of 0.01 to 0.02 /jim. It has been suggested (6) that 90% of the -fibres in human lungs are below 0.2 f,m so that .they can only be studied by transmission elec tron microscopy which, is a time consuming process. A study -of airborne chrysotile fibres in a textile factory was carried out by Rood and Streeter (39), sampling with membrane filters which were directly examined with a transmission electron microscope. Both lengths and diameters of the fibres were distributed near to lognormal with oK about 2.4. Lengths ranged from 0.5 to 20 pm (mode 0.74, median 1.6) and diameters 0.02 to 1.0 pm (mode 0.04, median 0.08) The aspect ratios were from 4 to 100 (median 20). They reckoned that 60% of all the fibres would have been invisible to a scanning electron microscope, which would show 70% of the fibres which were longer than 5 pm. A good optical microscope would reveal only 25% of the latter. Timbrell (26) used scanning electron .microscopy to examine samples of airborne dust and of lung dust from workers at an anthophyllite mine 259 HWBUI0001877 Davies, C. N.: Diseases Associated with the Inhalation of Asbestos Dust, Arh. hig. rada toksikol., Voi; 37 (1986) No. 2, pp 253--274. in Finland which were taken before it closed down in 1975. This form of asbestos is an amphiboie of low solubility having, rigid, straight rod-shaped fibres, with clean-cut ends, an ideal type for iris magnetic align ment method. Some figures taken from his paper' are shown in Table 1. The ranges of length and diameter of fibres recovered from lung tissue arc very similar to those of the airborne fibres but the distribu tions show that Ihe tissue fibres have more `long ones and more of larger diameter. This suggests that the normal lung clearance operated better for the shorter fibres than for the longer ones. Table 1. Fibres in airborne dust and lung dust from workers at an anthophyliite mine, length and diameter distributions were approximately lognormal (26). Air borne dust Fibre length .m Range Mode Median 0,4-200 1.4--3.1 2.4--2.9 3.8-10 Fibre diameter /tm Range ' Mode Median 0.1--50 0.2--0.4 0.4--0.7 1.9--2.2 . Range Lung dust ,' 0.5-100 rrc Mode 2.7--7.0 2.2--2.6 Median _ Range Mode 0.1-4.4 ' 0.4--0.5 1,5--2.0 Median _ Ayer and Zuniwalde (40) give length and diameter distributions of airborne fibres of several varieties of asbestos associated with indus trial processes. It is claimed (31) that a super-fine chrysolite asbestos gives a high incidence of mesothelioma by intrapleural innocu'lation but no data on diameter and length are given. In the discussion it was stated that this material contained not only extremely fine fibres' but also lumps of material compacted by milling; hence mass of injected dust is mot of great significance without analysis of shape, length and diameter of fibres. This is another reason for rejecting size selection of inhaled dust by aerodynamic diameter. Timbrdl (26) presents perspective diagrams of bivariate distributions of airborne fibres, tissue fibres and lung retention related to fibre length and diameter. These emphasize the futility of the 3 : .1 aspect ratio (9, 36, 37) suggesting that a figure of 15 to 20 might be more realistic in pinpointing the most dangerous fibres. The difficulties of laboriously preparing quantities of fibres scaled in length and diameter, for experi mental purposes and of analysing lung residues over realistic ranges of length and diameter have held up progress, The use of selective-mass 260 Davies, C. N\: Diseases Associated with the Inludation of Asbestos Dust. Aril. hig. rada toksikol,, Vol. 37 (1986) No. 2, pp. 253-274. ' samplers of ^respirable dust (50% penetration at 5 pm aerodynamic diameter) is unlikely to advance the understanding of the asbestos re lated diseases. . The handling of bivariate lognormal distributions of diameter and length of fibres has been discussed by Schneider and Holst (41), Thcri is some discussion of the possibility of finding fibre length, or length to diameter ratio from a series of measurements of penetration, over a wide range of values, of the same aerosol through a filtration system (42). Attempts 'to relate the disease-causing potential in mail of inhaled asbestos to the biological activity in animals, elicited by direct applica tion of asbestos fibres to tissue, are misleading because the important features of transfer of airborne fibres to lung tissue and their motion therein are short-circuited. This was emphasised by Robock and Klosterkotter (43) who suggest that chrysotiie has a greater cytotoxic effect than crocidolite whereas the latter is the greater health hazard because ils fibres can travel through lung tissue. For example, Pott (44, 45) has pre sented 3-dimensional diagrams of fibre length, diameter and a carcino genicity factor which do not give a reliable indication of human risk. The length and diameter, which are important factors in the human dise ases because fibre transport through air and tissue is decisive, are doubt fully associated with his carcinogenicity factor which is based mainly on implantation of fibres in animals. 6. WHAT ARE THE FEATURES OF ASBESTOS DISEASES RELEVANT TO SAMPLING PRACTICE? The following conclusions can be drawn from the experiments and observations which have been selected for mention in Sections 2 to 5 above; they are backed up by a considerable number of publications many of which are referred to in the papers quoted. In a sense, the vast body of research on asbestos diseases is disappointing since the impor tant directions given by early experiments have not been followed up and there is a general confusion as a result. Perhaps this was inevitable because so many factors are involved; however, it would be advantageous for much more attention to be given to the detailed physical nature of the dusts used .in animal experiments and of dust recovered from human iungs. This factor is basic to the design of sampling apparatus which need only record a very small selected fraction of the total airborne dust which is inhaled by persons handling asbestos. The physical nature of the inhaled dust is dependent on the variety of asbestos; the dust depo sited in the lungs depends rather broadly upon particle shape, length and diameter; the dust which causes the three diseases is more specifi cally related to particle shape, length and diameter, probably in a wnv which varies with 'the particular disease. 261 HWBUI0001878 Davies, C. N.: Diseases Associated with the Inhalation o! Asbestos Dust. Arh. hl. roda toksikol., Vol. 37 (19B6) No. 2, pp. 253-274. .......................... Accordingly, the selectivity of a satisfactory dust sampling system has 'to be much stricter than the selective sampling systems currently in use for insoluble dust, like quartz and coal, consisting of particles of relatively compact shape which produce illness, only if they attain the alveolated region of the human lung. A bonus following the produc tion of selective samplers for asbestos disease-causing fractions of air borne dust would be their adaptation for use as sources of supply of fractionated dust which could be used for animal experiments. In thinking upon these lines the first consideration is the differences between the varieties of asbestos, physical rather ithan chemical because specific chemical activity takes second place to the physical factors which govern the transport of fibres to (the connective tissues of the lungs, lymphatics and pleura. There are also indications that fibrous form, obviously for completely different reasons, may toe a key factor in cytotoxicity, this being supported by recent work on glass fibres, 7- VARIETIES OF ASBESTOS AND FIBROUS HABIT , A good account of the physical nature and properties of the six varielies of asbestos has been given by Badollet (46) including photo and electron micrographs. Chrysotile (white) asbestos is a serpentine rock and crocidolite (blue) asbestos, amosite, anthophyllite, tremolite and actinolite are amphiboles. An important point made in this paper is the breakdown ' of chrysotile into three varieties. Harsh chrysotile has straight, brittle needle-like fibres which are not curved: his Russian asbestos was in this category. Soft chrysotile (Arizona) has thin curved threads, very strong and of a silky nature which, like all asbestos fibres, split longitudinally. Soft chrysotile. is the most used in industry. The amphiboles resemble harsh chrysotile. A Canadian sample was classed , as semi-harsh. Hodgson (47) and Ayer and Zumwalde (40) give information about the occurrence, production and structure of asbestos varieties but omit to mention the distinct types of chrysotile. This may be important since the experimental production of mesotheliomas has been possible with amphiboles and Canadian chrysotile, but not with Rhodesian (19). The morphological differences are not described in the paper. . In general, soft chrysotile is assumed to have been used in experiments and recovered from human lungs; the possibility that harsh chrysotile, which is close to amphibole morphology, may have gone unnoticed and could account for anomalies is a real one. No doubt each amphibole variety of asbestos must cover a range of fibrous habit, just like chrysotile. It is not enough to discuss variations of disease parameters solely in terms of variety, unbacked by fibre shape and size measurements. Chemical differentiation follows the latter. 262 Davies, C. N.: Diseases Associated with the Inhalation of Asbestos Dust. Arh. hlg, rnda toksikol'., Vol. 37 (1986) No. 2, pp. 253-274. Timbrell (48) has pointed out a considerable difference between Afri can crocidolites. Fibres from North West Cape samples are thinner and shorter than those from the Transvaal; the latter fall under gravity nine times faster than the Cape fibres. This means, amongst othereffects, that the heavier Transvaal fibres penetrate to the alveolated region of the Jungs less than do the thin, shorter North West Cape fibres. This is associated by Timbre'll with the risk of mesothelioma being greater for the thin, shorter fibres. It is doubtful if the attain ment of actual alveoli is a prerequisite for the development of meso thelioma since fibres can penetrate the walls Of lung airways; the crucial concern is ability to 'traverse the lung parenchyma, aided by the tissue movements of breathing. 8. MECHANISMS OF THE CAUSATION OF DISEASE The curved, flexible, splayed fibres of soft chrysotile are up to 40 times more effective in causing asbestosis than the straight, rigid, smooth fibres of the amphiboles (25). A few of the inhaled fibres long er than 10 to 15 pm would pass in and out of the bronchioles (diameter 500 Bin) near enough to the surface of these airways to make contact. The straight amphibole fibres would collide with the surface less fre quently than chrysotile because they tend to align along the direction of airflow which is of too low a velocity to extend soft chrysotile fibres, these therefore have a better chance than needle-likc fibres of striking and penetrating the surface of the airway, of encountering connective tissue near the surface of the airway and causing asbestosis. The experiments with rats of Wagner and co-workers (19) in which both 'kinds of asbestos were dispersed indicated that asbestosis of much the same severity was caused by chrysotile and amphibole but there was much less chrysotile in the animals' lungs, the quantity not being dose-related. Concentrations were measured by a size selecting gravi metric sampler (50% penetration at 5 pm aerodynamic diameter) and the result demonstrates that this instrument is useless for asbestos. Clearly the chrysotile which caused the disease might collect in the hori zontal elutriator and not in the respirable dust. Perhaps the chryso tile fibres were more clumped than -those of the amphiboles, or perhaps they tangled with the plaites and previously deposited fibres. Lung carcinoma correlates with asbestosis (5). Asbestosis results from fewer fibres of chrysotile than amphibole (25); however (7) :lung carci noma follows chrysotile-induced asbestosis when there are more fibres in the lung than in the case of amphitoole-induced asbestosis. Mesothelioma necessitates the penetration of fibres from the wall of the bronchiole, through the lung parenchyma to the pleura. This is manifestly more probable for the needle-like fibres of amphibole than for the curved, splayed fibres of soft chrysotile which must tend to 263 HWBUI0001879 Davies, C. N,: Diseases Associaled with the Inhalation o{ Asbestos Dust. Arh. hig. rnda tofcsllcol., Vol. 37 (1986) No. 2, pp. 253--274. anchor themselves in tissue. Cyclic movements of the lung would readi ly move amphibole fibres but not chrysotile. These conclusions are summarised in Table 2; Study of the .table (sug gests very strongly that a chemical factor is optative in the fibres which cause Jung carcinoma and mesothelioma, possibly the same chain of reaction in each case. The animal experiments of Pickrell and coworkers (28) argue against a chemical factor being involved in asbestosis. Merle Stanton, in several publications, argues in favour of the fibrous nature prevailing over biochemistry as a cause of cytoxicity. 9. IDEAS FOR THE SELECTIVE SAMPLING OF AIRBORNE ASBESTOS A gradual. appreciation of the importance of the length of fibres, since the description of Gardner's work during the 1930's by Vorwatci and co-workers (14), is leading to attempts to estimate long fibres in ' Table 2. Mechanisms of causation of asbestos disease by fibres longer than 10--15 pm with diameters 0.1--4 pm* Variety of asbestos i Disease Soft chrysotile, Harsh chrysotile, soft amphiboles amphiboles ASBESTOS!S Amount in lungs Fibre transport by lung movement Location of lesion Small No Peribronchiolar Large Yes Distributed CARCINOMA Amount in lungs Large Small Fibre transport by Jung movement No Yes Location of lesion Epithelial, bronclviolar Lobe, segments MESOTEL10MA Amount in lungs Any Fibre transport by No lung movement Disease rare (does not Location of lesion reach the pleura) Small Yes Pleura * This table is confined to asbestos fibres too long to be transported by phagocytes which clean up deposits of shorter fibres. Entry of airbone fibres into alveoli is not essential for the causation of disease. Davies, C. N.: Diseases Associated with the Inhalation ot Asbestos Dust. Arh. hig. rada toksikol., Vol. 37 (1986) No. 2, pp. 233-274. airborne clouds in which short fibres afid compact dust particles con siderably preponderate. Up to about 1974 the idea unfortunately persist ed that gravimetric sampling through a horizontal elutriator or cyclone, with a 50% out at 5 pm aerodynamic diameter, would suit asbestos dust as well as coal and quartz for which it was designed. This is not so. Aerodynamic separation of long and short fibres is not satisfactory for the selective sampling of airborne asbestos because it depends mainly on the fibre diameter, d, and relatively slightly on its length (49). This can be seen from Table 3 which indicates the small change in Table 3. Stokes' diameter of elongated particles divided by the diameter. Length diam. Theory Prolate spheroids (oriented) Motion || Motion J_ to long to long axis axis Experimental (free fall) Asbestos (Stober) Glass CrooidoUte Amosile (Timbrcll) 10 1.94 1.62 1.88 1.65 1.7 20 2.18 1.77 2.12 1.78 1.8 50 2.48 1.96 2.48 1.99 1.9 too 2.68 2.09 2.79 2.15 2.0 Stakes' diameter, dpi,, which results from a large change in the ratio of length to diameter of fibrous particles. Theoretically, for long cylinders, there is no change at all, the value of dK,/d 'being about 3, depending on the Reynolds number. Experimental proof of the aerodynamic characterisation of fibres being by diameter rather than length is provided by experiments with a rather complicated Virtual Impaclor designed and constructed by Masada and co-workers (50). This divides an aerosol into three frac tions according to the aerodynamic diameters of its particles. The re sults with asbestos clearly demonstrate separation more by fibre dia meter than fibre length. The Stokes' diameter of a fibre (or particle) is equal to the aerodyna mic diameter divided by the square root of its density (v. Table 3) which lias to be much greater than the density of air. These diameters are related to the rate of fail of the fibre under gravity and therefore depend on its orientation. In the inertial spectrometer of Prodi and co-workers (52) clean air flows round a right angle bend and along a horizontal rectangular duct. 265 j j J HWBUI0001880 Davies, C. N,: Diseases Associated with the Inhalation of Asbestos Dust, Aril. hig. rada toksikol., Vol. 37 (1986) No. 2, pp. 2S3--274, 1 Fig. 1. Inertial spectrometer of Prodi and co-workers (52). Fibres align paral lel to the air flow mainly on account of the longitudinal acceleration of the air passing into the throat. Table 4. Density of asbestos fibres ' Badollet (46) Chrysotile Anthophyllite Tremoldte Actinolite Amosite Crocidolite 2.4 --2.6 g/cm8 2,85--3.1 2.9 --3.2 3.0 --3.2 3.1 --3.25 3.2 --3.3 'Hodgson (47) 2.55 -- -- -- 3.45 2.55 266 Davies. C. N.: Diseases Associated with the Inhalation of Asbestos Dust. Arh. hig. rada toksikol., Vol. 37 (1986) No. 1, pp. 253--274. Upstream of the 'bend a thin stream of aerosol is injected and the. particles are separated according to aerodynamic diameter as they round the bend. The separation is magnified after the bend as the aero sol flows along the duct of which the lower boundary consists of a membrane filter; the particles settle on the filter, the large ones not having so far to fall as the small owing to the inertial separation at the bend. When asbestos fibres wore sampled with this device they were, as would be expected, graded by diameter in the deposit along the filter. However there was also a very complete alignment of fibres along the flow lines; both the velocity gradient normal to the filter and the acceleration of particles approaching the bend contributed to this (Fig. 1). A commercially available Aerodynamic Particle .sizer (APS 33, TSI Inc) also orients fibres in an accelerating jet of air. All particles lag be hind the air, according to the aerodynamic diameter, on account of particle inertia. The instrument times each particle between two laser beams and from its velocity lag calculates the mass/drag ratio. Again it is the aerodynamic diameter which results so that the fibres are clas sed mainly on diameter. The instrument grew out of the work of Mazumder and co-workers (S3), whose SPART analyser measured the lag Of particles in air oscillating acoustically at about 27 KHz, using iaser-Doppler velocimetry. Wilson and Liu (54) also used LDV to measure the velocity lag of particles in an accelerating jet, but LDV was aban doned in the commercial instrument in favour of the simple time of transit, Hiller and co-workers (55) used the original SPART analyser for measuring deposition in the human respiratory tract simultaneously for particles of two different sizes. It is theoretically possible to separate fibres by length as was pointed out by Ogden and Walton (56). Cylinders fall under gravity, not verti cally but at an angle to the vertical which is related to the inclination of the cylinder, which is maintained during falling, and to the length to diameter ratio. Experiments in glycerol showed that the angles agree with values predicted by theory for prolate ellipsoids of revolution. It is doubtful if this could be applied to asbestos fibres because the form is geometrically imperfect and the falling velocities of the fine fibres would be low and there would be diffusion. Optical differentiation is possible and has been discussed by Seger (57). Fibrous particles when illuminated by a narrow beam in a plane of incidence at right angles to the fibre length scatter most of the light in the same plane. In his arrangement a laser beam was used and four detectors looked for scattered light. Presence of a fibre was indi cated by a streak of scattered light in the plane of incidence. Compact particles produce equal scattering in all directions at right angles to the incident beam (Fig. 2). 267 u itiii" I'-'f 'Tirwviwifti myarj HWBUI0001881 Davies. C. N.; Diseases Associated with the Inhalation of Asbestos Dust. Arh. hig. rnda toksikol., Vol. 37 (1986) No. 2, pp. 253--274. Davies, C. N.: Diseases Associated with the Inhalation ot Asbestos Dust, Arh. hlg. rada tokslkoL Vol. 37 (19861 No. 2, pp. 253-274. t Fig. 2. Scattering of light by a fibre and by a compact particle (simplified). Light scattering used in conjunction with magnetic alignment of fibres differentiates fibres clearly, on the above basis. Magnetic align ment of asbestos fibres has been studied by Timbrell (58--60). The fi bres can only be aligned if they aire suspended in air or liquid but the direction of alignment relative to the field is variable and unpredictable. In special cases this method is useful, but not for selective sampling. It has been applied, for example, in assessing a sample of aisbestos on a membrane filter by measuring the light scattered forwards up a microscope tube while rotating the magnetically aligned fibre prepara tion (Vickers, 1788 rapid fibre counter); there have been difficulties with fibre counts below 100 mm--* (61). Selection by electrical mobility was first tried by Zebel and co-work ers (62). The aerosol was fed past a corona discharge producing positive ions which were picked up by particles. The particles then passed through a parallel plate electrical mobility spectrometer in which the Big. 3. System of Zebel and Hochrainer (63) for separating fibres and isome tric particles. The electric field (--20 kV) lines of force are marked with arrows. They cross the air flow lines which are vertically downwards and draw the charged particles from the periphery to the centre of the filter. Fibres carry greater charges than compact particles and are found closer to the centre. 269 HWBUI0001882 Davies, C. W: Diseases Associated with the Inhalation of Asbestos Dust. Arh. big. rada toksikoi., Vol. 37 (1986) No, 2, pp. 253--274: ........................... particles deposited on the negative plate. Long fibres collect more ions than short ones while passing the corona discharge, hence they deposit first in the spectrometer with shorter fibres further downstream, fol lowed by particles of compact shape carrying minimal charges. An improved version of tile apparatus was later described by Zebel and Hochrainer (63), It was now built on a cylindrical plan with improv ed charging; the charged aerosol particles were led, in a thin layer, down the inside surface of the cylinder by using a flow of dean air, very carefully introduced to avoid .mixing. The cylinder was earthed and a grid, covered with filter paper formed the base of the cylinder which was charged to --20 kV. The inhomogenous field drew ail particles towards the centre of the filter where they were spread out radially, the fibres with the highest mobility being nearest to the centre. This apparatus works well but it is doubtful how it would grade soft chrysotile (Fig. 3). Work on the automation of fibre counting by image analysis has been in progress for several years. The method which has received most development is Magiscan in which a television camera records optical microscope fields of a membrane filter sample. The picture is digitised in levels of gray and fed to a microprocessor system programmed to read out fibre length selectively. The current stage of development is described by Kenny (64). Use with an electron microscope is projected. , 10. AEROSOL GENERATORS FOR FIBROUS PARTICLES Timbrett, Hyetl and Skidmore (65) describe a piston fed disperser for putting up aerosols of the UICC reference samples of asbestos. It will cope with all varieties, subject to small adjustments. Concentrations of about 12 mg/ms in 12 I/min of air obtained of particles below 5 /<m aerodynamic diameter which represents about 80/o of the total airborne mass. Fibres up to 50 /<m long are emitted, when the charge of asbestos contains lengths up to 200 p:m as well as large floes with which the dis perser deals without difficulty; even the entwined, curved fibres of. chrysotile are separated. The output of dust is well suited to inhalation experiments. i Ilounam (66) describes a small air jet blowing over the top of a tube up which a small plug of asbestos is driven by a screw. It will deal with only a few mg of sample and disperse it over an hour or two. It is a useful means of dispersing neutron activated asbestos. Although they do not discuss asbestos, a good account of the beha viour of fluidised bed dust generators is given by Willeke and co-work ers (67). Guichard (68) gives detailed designs; also Carpenter and Yerkes (69)whose apparatus delivers steadily 125 mg/m5 in 0.28 mi'/min of air. Boucher and Lua (70) have a system yielding very high concentrations (4 g/m5) which breaks up aggregates. An alternative arrangement to a 270 Davies,'C. N.: Diseases Associated with the Inhalation ot Asbestos Dust. Arh. hig. rada toksikoL, Vol. 37 (1986) No. 2, pp. 253-274. fluidised bed, which also breaks tup aggregates, has been described by Seehars and Hochrainer (71). The behaviour of fluidised beds as a source of glass fibre aerosols has been described by Carpenter and. co-workers (12). Spurny, Gentry and Stober (73) point put that the flow velocities need ed to 'generate an aerosol of fine fibres are too low for a bed lo fluidise; hence no aerosol can be generated. In order to overcome this problem they arranged to agitate the vessel containing the bed at frequencies from 15 to 120 Hz with amplitudes of 50 to 1000 /<m. This system worked well and samples on nuclepore filters of amosite and chrysotile obtained in this way are illustrated. Spumy (74) discusses fibre generation and length classification in great detail with 82 references and some fine photographs of fibres. Pickrell and co-workers (IS) constructed a generator for glass fibres. Such fibres which are longer than 20 //>m are retained more tenaciously in the luhgs than fibres below 5 ;m in length, presumably due to frus trated phagocytosis. Commercial glass fibre mat was minced, suspend ed in polyethylene glycol, formed into blocks and frozen. The blocks were then sectioned with a microtome, suspended in water, 100 steel pellets added, dried and finally dispersed in fluidised bed gene rators. Concentrations of aerosol of 40 mg/m5 resulted of which about 2/3 was in fibres below 5 pm aerodynamic diameter. The diameter of the fibres was about 2 pim and there were some 2000/cm5 longer than 20 um. Friedrichs (1) discusses problems which arise in administering to ani mals fibres of asbestos, glass and other substances. He gives a nomo gram relating diameter, length and density of fibres to the number per mg. Citing Pott's experiments, he relates the probability of tumour for mation following intratracheal injection of rats, to the dose; thresholds and maxima are best shown by plotting against the number of fibres administered. References 1. Friedrichs, K. H.: Staub. Reinh. Luft, 38 (1978) 490--493. 2. Walton, W. H.: Ann. Occup. Hyg., 25 (1982) 117--247. 3. Spurny, K., Stober, W. et ai: Sci. Total Environ., 11 (1979) 1--40. 4. Weller, W.: Staub. Reinh. Luft, 38 (1978) 481-485. 5. Doll, R.: Br. J. Ind. Med., 12 (1955) 81--86. 6. Davies, C. N.: J. Aerosol Soi., 10 (1978) 477--513. (Ann. Occup. Hyg., 13 (1970) 241--245). 7. Gilson, J. C.: Proc. Roy. Soc. Med., 66 (1973) 395--403. 8. British Occupational Hygiene Society: Ann. Occup, Hyg., 11 (1968) 47--69. 9. Luxon, S.: Ann. Occup. Hyg., 13 (1970) 23--24. 10. Health and Safety Commission: Final Report of the Advisory Committee on Asbestos, HMSO, London, 1979. 27 V HWBUI0001883 Davies, C. N.: Diseases Associated with the Inhalation of Asbestos Dust. Arh. hig. rada loksikol., Vol. 37 (1986) No. 1, pp. 253--274. 11. British Occupational Hygiene Society: Ann. Occup. 'Hyg., 16 (1973) 1--5. 12. British Occupational Hygiene Society: Arm. Occup. 'Hyg., 27 (1983) 1--55. 13. Stellingwerf, 1.: Atm. Occup. Hyg., 28 (1984) 354--356, 14. Vorwald. A. J., Durkan, T. M., Pratt, P. C.: Arab. Isjd.rHyg. Occup. Med., 3 (1951) 1-43. 15. Beattie, J., Knox, 1. F.: In Inhaled Particles and Vapours, Ed. C. N. Davies, Pergamon Press, Oxford, 1961, pp. 419--433. 16. Beattie, J.: In Inhaled Particles and Vapours, Ed. C. N. Davies, Perga- man Press, Oxford 1961, p. 434, p. 442. 17. Zielhuis, R, L.: Public Health Risks of Exposure to Asbestos, Pergamoli Pwee Oxford 197."? 18. Wagner, J, C.: The Practitioner, 223 (1979) 29. 19. Wagner, J. C., Berry, G., Skidmore, J. W., Timbrell, V.: Br. J. Cancer, 29 (1974) 252--269. 20. Davies, C. N.: In "Annual Review of Medicine, Ed. D. A. Rytand and W. Crager, 1957, pp. 323--348. 21. Beck, E. G., Bruch, J., Friedrichs, K. H., Hilsclw:, W., Pott, F,: In "In haled Particles III, Ed. W. H. Walton, Unwins, Old Woking, 1971, pp. 477-487. 22. Conning, D. M., Hayes, M. J., Styles, J. A., Nicholas, J. A.: In '-Inhaled Particles III, Ed. W. H. Walton, Unwins, Old Woking, 1971, pp. 499--506. 23. Morgan, A., Evans, J. C., Holmes, A.: In "Inhaled Particles IV, Ed.. W. ,H. Waiiton, Pergamon Press, Oxford 1977, pp. 259--274. 24. Monchaux, G., Bignon, J. et al.: In "Inhaled Particles V, Ed. W. H. Wal-ton, Vergmnon Piress, Oxford 3982, jpp. 309--318. (Ann. Occup. Hyg., 26) 25. Wagner, J. C., Pooley, F. D. et at: In "Inhaled Particles V,'Ed. W. H. Walton, Pergamon, Oxford 1982, pp.. 423--431. (Ann. Occup. Hyg., 26) 26. Timbrell, V.: In .-Inhaled Particles V, Ed. W. II. Walton, Pergamon, Ox ford 1982, pp. 347--369. (Ann. Occup. Hyg., 26) 27. Balser, J, L.: In "Inhaled Particles III, Ed. W. H. Wa'iton, Unwins, Old Woking, 1971, p. 57. 28. Pickrell, J, A., Hill, J. O. et al: In "Inhalation Toxicity Research Institute, Annual Report, 1978--1979. National Technical Information Service, US Department of Commerce, Sprfagfiokl, 1980, pp. 509--513. 29. Timbrell, V., llyett, A. W., Skidmore, J. A.: Arm. Ocoup. Hyg., 11 (1968) 273--281. 30. Harris, R. L,, Timbrell, V.: In "Inhaled Particles IV, Ed. W. H. Walton, Pergamon Press, Oxford 1977, pp. 75--89. 31. Wagner, J. C., Berry, G. et al: In "Inhaled Particles IV, Ed. W. H. Wal ton, Pergamon Press, Oxford 1977, pp. 647--654. 32. Bolton, R. F., Davis, J. M. G., Donaldson, K., Wright, A.: In "Inhaled Par ticles V, Ed. W. H. Walton, Pergamon, Oxford 1982, pp. 569--582. (Ann. Occup. Hyg., 26) 33. Stanton, M, F., Wrench, C.: J. Natl. Cancer Inst., 48 (1972) 797--821. 34. Doll, R.: J. Roy. Statistical Soc. A., 134 (1971) 133--166,: 35. Stumphius, J., Meyer, P. B.: Ann. Occup. Hyg., 11 (1968) 283--293. 36. Rowlands, N., Gibbs, G. W., McDonald, A. D.: In "Inhaled Particles V<, Ed. W. H. Walton, Pergamon, Oxford 1982, pp. 411--415. (Ann. Occup. 37. 'McDomld, A. D., McDonald, 1. C., Pooley, F. D.: In "Inhaled. Particles V, Ed. W. H. Walton, Pergamon, Oxford 1982, pp. 417--422. (Ann. Occup. 38. ]{annerstein, M., Churg, J.: Environ. Health Perspect., 34 (1980) 31--36. 272 Davies, C. N.: Diseases Associated with the Inhalation of Asbestos Dust. Arh. hig. rada toksikel., Vol. 37 (1986) No. 2, pp. 253--274. 39. Rood, A. P., Streeter, R. R: Ann. Ocoup. Hyg., 28 (1984) 333--339. 40. Ayer, H., Zumwalde, R. D.: In "Generation of Aerosols, Ed. K. Willeke, Ann. Arbor, Michigan, 1980, pp. 235--256. 41. Schneider, T., Holst, E.: J. Aerosol. Soi., 14 (1983) 1. 42. Yu, P. Y,, Gentry, J. W.: 3. Aerosol. Soi., 13 (1982) 200--205. 43. Robock, K,, Klosterkotter, W.: In "Inhaled Particles III, Ed. W. H. Wal ton, Unwin, Old Woking 1971, pp. 465-475. 44. Pott, F.: Staub-Reinh. Luft, 38 (1978) 486--490. 45. Pott, F.: In Umwelthygiene, Girardet, Essen, 13 (1980) 31--66. 46. Badollet, M. S.: Canadian Mining and Mcttalurgical Bull, Transactions, 54 (1951) 151--160. 47. Hodgson, A. A.: Phil. Trans. Roy. Soc. London, 286 (1917) 611--624. 48. Timbrell, V.: In "Assessment of Airborne Particles Ed. T. Mercer, P. Mor row, W. Stober, Thomas, Springfield, Illinois 1972, pp. 429--445. 49. Stober, W., Flaschbart, H., Hochrainer, D.: Staub. Reinh. Luft, 30 (1970) 277--285. 50. Masuda, II., Hochrainer, D,, Stober, W.: J. Aerosol Soi., 10 (1979) 275--287. 51. Davies, C. N.: J. Aerosol Soi 10 (1978) 477--513. 52. Prodi, V., de Zaiacomo, T., Hochrainer, D., Spumy, K.: J. Aerosol Sci., 13 (1982) 49--58. 53. Mazumder, M. K., Ware, R. E., Wilson, J. D., Renninger, R. G., Hiller, R. C., McLeod, P. C., Raible, R. W., Testerman, M. K.: J. Aerosol Sci., 10 (1979) 561--569. 54. Wilson, J. C., Liu, B. Y. H.: J. Aerosol Sci., 11 .(1980) 139--150. 55. Hiller, F. C., Mazumder, M. K., Wilson, J. D., McLeod, P. C., Bone, R, C.: J. Aerosol Soi., 13 (1982) 337--343. 56. Ogden, T. L., Walton, W. H.: Ann. Occup. Hyg., 18 (1975) 157--160. 57. Seger, G.: J. Aerosol Soi., 12 (1981) 219--220. 58. Timbrell, V.: Microscope, 20 (1972) 365--368. 59. Timbrell, V.: Ann. Occup. Hyg., 18 (1975) 299--311. 60. Timbrell, V.: Filtration and Separation, 14 (1977) 242. 61. Veritl, K. J.: Ann. Ocoup. Hyg., 21 (1983) 111. 62. Zebel, G., Hochrainer, D., Boose, C.: J. Aerosol Soi., 8 (1977) 205--213. 63. Zebel, G., Hochrainer, D.: J. Aerosol Soi., 10 (1979) 245. 64. Kenny, L. C.: Ann. Occup. Hyg., 28 (1984) 401--415. 65. Timbrell, V., Hyett, A. W., Skidmore, J. A.: Ann. Ocoup. Hyg., 11 (1968) 273--281. 66. Hounam, R. F.: Ann. Ocoup. Hyg., 14 (1971) 329--335. 67. Willeke, K., Lo, C. S. K., Whitby, K. T.: J. Aerosol. Sci., 5 (1974) 449--555. 68. Guichard, J. C.: In "Fine Partioles, Ed. B. Y. H. Liu, Academic Press, New York, 1976, pp, 174--193. 69. Carpenter, R. L., Pickrell, .1. A. el al.: "Inhalation Toxicity Research Inst. Annual Report 1979--1980. National Technical Information Service, US Department of Commerce, Springfield, USA, 1980, pp. 501--505. 70. Boucher, R. F., Lua, A. C.: J. Aerosol Sci., 13 (1982) 499--511. 71. Seehars, H. D., Hochrainer, D.: Staub. Reinh. Luft, 41 (1981) 466--472. 72. Carpenter, R. L., Yerkes, K. L.: Inhalation Toxicity Research Inst. Annual Report 1978--1979. National Technical Information Service, US Depart ment of Commerce,-Springfield, USA, 1979, pp. 327--330. 73. Spumy, K. R., Gentry, J. IF., Stober, IP..* In "Fundamentals of Aerosol Science. Ed. D. T. Shaw, Wiley, New York, 1978, Chapter 5, pp. 257--324. 273 HWBUI0001884 Daviss,' C. N.i Diseases Associated with the Inhalation o! Asbestos Dust. Arh. hig. rada toksikol., Vbl. 37 (1986) No. 2, pp. 253-274. 74. Spumy, K. R.: In "Generation o Aerosols. Ed. K. Willeke, Ann Arbor, 1980 USA, Chapter 13, pp. 259--298. 75. Pickrell, J. A., Carpenter, R. L. et ai: In >>Inhal,ation Toxicity Research Institute, Annual Report, 1978--1979. National .Tecimicai Information Service, US Department of Commerce, Springfield, USA, 1979, pp. 550 --554. i j,-.. Saletak BOLESTI POVEZANE S UDISANJEM AZBESTNE PRASINE Proudavanje literature o azbestozi upuduje na to da bolest izaziva udisan.je azbestndh vlakana duitih od 10--15 pm. Krada vlakna uklanjaju se preko fagocita iz pluda. Me&l krizotil mnogo je aktivniji u pludima od biio koje druge vrste azbesta u izazivanju azbestoze. Vaznost topljivosti krizotila, navodno vede nego u drugih vrsta azbesta, niie sigurna jer krizotil nije toksidan za fagocite a vlakna mogu biti izuzetno tina i teSko ih je otkriti cak i uz pomod dobrog transmisij'skog elektronskog mikroskopa. Isliod moze rezultirati usitnjavanjean Vlakana po du2ini prije negoli smalljerajern njihova promjera. Rak pluca takoder izazivaju duga fina vlakna krizotila. Zapodinje peribron- hijalno jer se izvijesna, kosa vlakna ne probijaju kroz pluda uz pomoc rit- mldkih respiratomih pokreta. Tvrda, iglidasta, glatka amfibolna vlakna pro- laze kroz pludno tkivo i, ako su dovoljno duga da izbjegnu fagocitozu, uzro kuju karcinom. Mezoteliom pleure izaziva udisanje dugih amfibolnih vlakana koja su iz diSnih puteva doSla u pleuru. Moze biti izazvan direktnom injekcijom ili aplikacijom azbestnih krizolilnih vlakana bilo koje duiine u plcsuru Jivotin ja, ali ne nastaje udisamjcm jer sc izvijena, kosa vlakna mekog krizotila ukapaju u pludno tkivo i ne piituju do pleure. Selektivno snkupljanje uzoraka azbestne prasine iz zraka nephodno je da bi se iz znatne kohdtne'kratkih vlakana praSine koju uklanjaju fagociti prije nego izazove oStedenja, izdvojio mall dio vlakana odgovornih za izazivanje bolesti. Selektivni sakupljad uzoraka mora sakupljati i zadrzati vlakna duza od 10--15 pm, promjera u rasponu 0,1--0,5 pm. Nema svrhe selckctamrati vlak na na osnovi njihovog aerodinamiikog promjera jer je taj kriterij. neosjet- Ijiv na du&'inu vlakana. Opisani su neki noviji sistemi sakupijanja i sclekcio- riiranja uzoraka. 1 : Pilcox Hall, Tmdring, Essex, Velika Britanja Primljeno 10. II. 1986. 274 " .. rSS *. ~! Arh. hig. rada toksikol., 37 (1986) 275--284. Prikaz UDK 614.87:621.3.038.8 IDENTIFIKACIJA I MOTRENJE TOKSICKIH KOMPONENATA U FLINSKOJ FAZI POMOCU LASERSKE FOTOAKUSTICNE SPEKTROSKOPIJE D. D. Bi canid1, I. Simonov i d" /j F. Harren' Odjel za jiziku i meteorologiju, SveuciliStc Wageningen, Wageningen, Nizozemska', Zavod za nuklearnu medicinu, Medicinski jakidtat SveudiliSta u Zagrebu, Klinicki bolnicki cenlar, Zagreb* i Odjel za lasersku i molekulamu ji ziku, Sveuciliste u Nijmegenu, Nijmegen, Nizozemska3 (Primljeno 18. IV 1986) U ovom se cianku navode neki osnovni principi laserske foloakusticne spektroskopije u plins'koj fazi, kao i prim jenc 1c metode u proudavanjima problema opdenile oneciscenosli zraka. Tehnoloski razvoj na polju lasera i elektronike dosegao je razinu koja omoguduje realizaciju jednog prakticnog, ekonomicnog aparata (monitor-analizator) visoke osjctljivosti cijc se funkeioniranje zasniva na fotoakustifinom principu. Svrha ovog clanka je da zainteresiranim cilaocima pomogne pri dobivanju osnovnih uvida u korisnost upotrebe fotoakustidne spektroskopije. Britain smo se ogranicili na osnovnc fizicke princtipe i samo neke od rezultata zabiljezcnih u radu s pliimskini komponem tama. Pojava povecanih koncentracija raanih toksickih komponenata u zraku posljedica je sve veceg stupnja apde oneciscenosli atmosferc. Ovakva situaeija postaje (ovisno o Industr.ijskim i geografskim uvjetima) sve ozbiljniji zdravstveni problem izlozenog stanovnistva, pa se nekoli'ko zadnjih godina opaza postepena tendeneija ka smizavanju ntaksimalno dopustenih vrijednosti koncentracija, Usporedo s tim trendom namede se, sam po sebi, i 'sve akutnij.i pro blem potrebe za metodom kontrole atmosferskih i industrijskih polutanata. Realizacija ovakvih napora omogucila bi bolji uvid u niz fiziokih i kemijskih procesa odgovornih za fenomene kao sto su na primjer kisela kiSa, produkeija sanoga ltd. Slijecledi su faktori vazni kao kriterij prilikom izbora najprikladinije metode: -- sposobnost detektiranja sto nizeg nivoa koncentracija (l.zv. detekcijska granica); -- selektivnost ili specifidnost, tj. sposobnost detektiranja odredene supstaneije uz istodobnu prisutnost drugih interferirajucih kompo nenata; 27.5 HWBUI0001885