Document ZJRQVqeykqOn92B1BXb9pgdgp

Aw. trap Hft, Vol . No. t, pf. 1-55, JM3 Prated i* Crest main. BRITISH OCCUPATIONAL HYGIENE SOCIETY REPORT FROM THE COMMITTEE ON ASBESTOS A STUDY OF THE HEALTH EXPERIENCE IN TWO LUC. ASBESTOS FACTORIES BOHS COMMITTEE ON ASBESTOS (1977-1982) S. A. Roach (Chairman), S. Holmes (Technical Secretary), W. H. A. Beverley, 1 L. Bonsall, L. H. Capel, R. D. Hunt, M. Jacobsen. J. G. Morris, W. H. Smither, J. Steel, R. Sykes, S. J. Silk (Obs^-ver). Corresponding member H. C. Lewinsohn. Advisers C. G. Addingley,* J. C, Gilson, J. C. McDonald. Abstract - Radiological, physiological and clinical data from two asbestos factones have been examined in an effort to establish what cumulative exposure to asbestos dust is associated with the first signs of adverse pulmonary etfects. Persons it eluded in the present study had been exposed to asbestos for at least 10 yr and had ail started work with asbestos after 1950, by which time regular recording of dust concentrations bad become established The type of asbestos involved was predominantly chrvsotiie. bet in both ractories some crocidolitc had been processed at some stage during the study period Three physicians made independent assessments of 'early* and *!ate` chest radiographs from 295 men from Factory A and 351 men and women from Factory B. Lung function and other medical data were supplied by the Medical Officers of the factories concerned The dust data from Factory A made possible an assessment of the relationship ofcumulative exposure to the onset of adverse pulmonary effects The nature ofthe data from Factory B precluded such an exercise. The radiological results from Factory A showed an association between the occurrence of parenchymal changes (profusion of combined opacities I and estimates of cumulative exposure. The evidence from Factory B generally supported this finding Lung function measurements indicated that levels of FP, and FVC among men who had accumulated relatively high exposures in Factory n were lower than for thoe who had receive.1 only low exposures. The correlations with dust exposure were significant at rhe 6*. level Investigations were carried out into the relationships between dust concentrations measured by present-day methods and those used in earlier year. The estimated exposures involve many uncertainties but are probably the best available for such a retrospective study of asbestos-related disease They relate to stanc sampling, not personal sampling The results .ndicated that, at Factory A. the probability of occurrence of any one of seven defined Adverse Effects in association with a cumulative exposure ofless than 25 fibre-yr.ml was less than 2%. based on static sampling h> the membrane filter method For exposures less than SO fibre-yr/ml the fig ire was 7,, and for exposures up lo 100 fibre-yr/ml n was 17-20";. This does not necessarily imply that asbestos dust exposure caused the observed effects Cancer risks were outside the scope of this particular study The Committee wishes to recced with deep regret Ihe death of Dr C. G. Aikhmolcy in October 1978. 2 liOflS 1. INTRODUCTION The U.K. hygiene standard for cbryaotile asbestos adopted fcr use with The Asbestos Regulations (1969) was based on a report published by the British Occupational Hygiene Society (1968) describing a study on a cohort of men in an asbestos textile factors iFactory A), first employed since i January 1933 and still employed on 30 June 1966, w.th at least 10 yr service in asbestos areas The recommended standard was m the form of a total integrated exposure (dust concentration in fibres per milhhtre of air muSip!fcd b> the lime ofexposure m working years j considered to carry a I % risk of a worker exhibiting the earliest signs of the possible effect ot asbestos exposure The figure arrived at was 100 fibre-yr. mL giving an exposure of 2 fibres'ml (by the counting procedures then current! ove* a working life of 50 yr, and it is this limiting concentration which has been quoted in fhe literature of many countries, ft is unusual, of course, for any individual to be exposed for so xr.g a period in modem industrial practice This 196* standard has been the subject ofa number ofcriticisms over the years, the main ones bang the follow rag fat T he cohort wash used in that persons fulfilimg the cohort definition, i.e at least JO v r set vice since 1933. were not included if that exposure had ceased pn^r to 30 June 1966 as a result of nbesto* areas o* death (b ? Similarly, persons reacting 10 yr service after 30 June 1966. even by as little as one month were also excluded tc The earliest sign of adverse effect wav taker, to be the presence of persistent bava? :lrv but this n not always so there art ether early signs which fmgb* well precede fi'r* tn certain caw. ji The daia had been collected from one asbestos textile factory only if * Du; mg the period covered b> she stud, vorse crocidohic had been ved f. it r (actor* npovure to which mav have influenced the findings * Avhrssos^asufHsased cancer risks had m * berr- considered Mme icccnUy a food deal of evtra inroerr-Ar--'e. has become available on the ad *rrur effects of exposure to asbestos 0.kfr.<~%uc methods base tmpro'ed. in \urttcular by i he euemivr use of lung jfoivcr;;?;- measarements and the ad option of an agreed classification for the assessment of asbestos workers' X-ray nimv itvnxv*tKis*i Uwxi Omci. I92i tn *dd.v.r. constdc:abiy more experience has been gamed in dust sampling and analysis for she measurement of exposure and some additional data have become available from a second factory (Factory Bt The fust attempt to up-date the 196S dau was made by a reconstituted Sub committee between 19TI and 19 *0 using a group from Factory A extended to rnebter rrtr? v* b,'> had completed 10 yr service betwerr V June 1966 and 3! December i9'2 Mm who had left the factors between those du'.t* ere also included The results of this **. *ct described by Bi*'' r* < 19 : ; iJ! *0k * *-* *?e. eif Mi. iv ' j u c t* thf - T ni P F ; 51 % BfiMS Ct>MMn tfl t a Bf IMSComm.uee Ashevto- up ti.i `: De-:r~*>r- 19-6 The foI.oamg step* were 0uS322 Health experience ra two U K. asbestt** factory* 3 ;(aj In addition to the cohort from Factory A. (all ofthem men), a second cohort was studied comprising men and women from Factory B. Some members of the second cohort hud worked on the production of textiles and others on friction materials. (bi Both cohorts were confined to people who had not been exposed to asbestos before 1 January 1951, because no dust measurement results were available prior to that date, and who had at least 10 yr accumulated exposure by 31 December 1976. Eforts were made to trace those who had left before that date so that they could return for an X-ray and clinical examinaion and, in the case of those who had died, the cause of death was ascertained as far as possible. By doing so, it was hoped in aeei some of the criticisms of the 1968 study. It should be noted that, while chrysotile was by far the most predominant fibre used, some crocidolite was processed at both factories at some time during the study period. It is not possible to estimate what proportions of the respective cohorts were exposed to this latter fibre. (ci Efforts were made to calculate the dust exposure for each individual in each cohort, year by year, adjusted on an agreed basis to take into account the changes in dust sampling and analysis winch had taken place over the 25 yr period of the study. id i A: the outset, the object of the Committee was to review the hygiene standard for chrysotile asbestos dust, but the health experience over recent years has indicated that such a review would be of limited value if it did not take some account of maiignar.^ * Long-term, wide-ranging prospective epidemiological studies of cohorts followed throughout their lives would be needed to support a hygiene standard designed to reduce the incidence of malignancy attributed to asbestos exposure and. since malignancy has multifactor sal causes, parameters other than asbestos exposure would need also to be recorded and considered. The outstanding factor is cigarette smoking and there is evidence that smoking potentiates the risk of lung cancer m asbestos-exposed w orkers. the effects are not simply additive. In the cohorts studied by the Committee detailed mortality records were not generally available. The Committee therefore decided to confine itself to a study of morbidity data with a view to obtaining a bettei understanding of the adve rse effects of asbestos exposure during life, bearing in mmd that an ongoing mortality study had been established for many years at Factory A. Iasi reported by PtTO ei oi (19771. tej I he work of the re-conrtituted BOHS Committee was to some degree overtaken by events An Advisory Committee on Asbestos was set up by the Health and Safety Commission jHSChn 1976 and a Medical Working Group of that Committee was giver. the task of rev tew mg all the available information on asbestos and health and making appropriate recommendations Although the BOHS Committee's study was still at an early stage, it provided the HSC Medical Working Group with an interim statement in April 1978 outlining the progress which had been made up to that time and th < w js no doubt taken into account by the HSC Medical Working Group when rep. to its parent Advisory Corimtttee on Asbestos W'hcn the Adviso-* Comm :;e on Asbestos issued its I inal Report in October 1979. it recommended that the te-rr. hygiene standard' should be replaced by "control limit" for the assessment of exposure to as nest os dust, because, in its view, there is no apparent threshold below which exposure entails no risk to human health. It states that `this new concept is intended to represent a realistic level of airborne concentration of dust, closely associated with the relevant legislation, above which no persons should be occupationally exposed' (HSC. 197% 0US323 4 iOHS Commit?** ok Awettm 3. THE MEDICAL DATA The medical information which has heat analysed for the BOHS Committee is described in detail in Appendix 3. The main features were: (a) Pairs of chest radiographs comprising the earliest post-1950 film and the latest pre-1977 film for each person. These, along with 'control' films, Were presented in turn to three physicians of acknowledged expertise in this particular field who were asked to classify them independently in accordance with the 1LO U/C (1971) international Classification of Radiographs of Pneumoconioses. A more detailed study of the many other intermediate films would be necessary to pin-point the first evidence of radiological changes more dearly. At Factory A workers had chest radiographs taken every 3 yr from 1951 to 1967 and annually thereafter. At Factory B workers had chest radiographs taken every 2 yr from 1951 and in some cases more often. (b) All available information on medical examinations and Sung function measurements carried out over the period covered by the study was provided by the medical officers of the respective companies. At Factory A, lung function tests were introduced in 1967 and had been carried out every 2 yr. At Factory B, lung function tests had been carried out every 2 yr since 1960. In order to arrive at an agreed interpretation of all these data, the medical members of the Committee were asked to meet as a Working Group under the chairmanship of Dr W. J. Smither `to advise on the first medical indication or indications of adverse effects on the lungs'. A report of their deliberations is given in Appendix 1. 4 DUST CONCENTRATIONS An extensive account of the history of dust measurement techniques employed in the asbestos industry is given by Walton (1982). (a) Factory A The Cr.sella Thermal Precipitator (TP) was used at Factory A from 1951 to I960 and ail monitoring was `static'; that is, the sampling was conducted with a free-standmg sampling instrument having the air inlet at head height and the instrument placed on a stand in a fixed position, near the operative, but without interfering with his movements in carrying out his task. The samples after `ashing' of the coverslips were counted at high magnification (800-1000 x) under dark-ground reflected light using a 4 mm objective.* Fibres were not looked for specifically and all particles judged to have a projected diameter of 0.5 jxm and above were included in the count. Between 1960 and 1964, the Long Running Thermal Precipitator (LRTP) was used and. again, monitoring was static. With this instrument fibres were counted at about 500 x magnification and the results were expressed in fibres'ml, using the convention that only fibres greater than 5 jim long and having an aspect ratio greater than 3.1 were counted Later, when guidance notes on counting were published (Asbestosis Research Council, 1971). a further convention limiting the count to fibres less than In the carher report) BOHS, 196S)it *a< Mated, incorrectly, that the Thermal Precipitator samples were counted using a 2 mm objective 0uS324 Health experience in two UK. asbestos factories $ 3 #im in diameter was adopted. This latter convention is not considered to have affected the Factory A counts to any significant degree. From 1964 to 1974, static monitoring continued, but using a membrane filter sampling instrument or a Royco Automatic Particle Counter. The membrane filter samples were counted for fibres at about 500 x magnification under phase contrast conditions. The Royco instrument detects both particles and fibres but was set to produce results comparable with membrane filter fibre counts. After 1974, membrane filters were used exclusively and a change in technique was introduced in that counting was restricted to the area within a British Standard Graticule (BS 3625, 1963) mounted in the microscope eyepiece, instead of covering whole microscope fields of view. This had the effect of increasing the numbers of fibres counted per unit area of the slide by a factor of about 2 (Beckett et at, 1976), so the fibre concentrations calculated in the 1960s (used in the 1968 BOHS study) would need to be multiplied by 2 to compare them with counts taken today. In an attempt to relate the early figures to 1977 membrane filter counts, an investigation was carried out at Factory A, running ail instruments side by side (Appendix 2A). The samples obtained from the older instruments were counted using identical techniques to those employed in the factory when those instruments were in use. The following approximate relationships were found, all relating to static sampling: 1977 Membrane Filter = 0.07 TP 1977 Membrane Filler = 2.2 LRTP 1977 Membrane Filter = 2 x 1964-1974 Membrane Filter These conversion factors were used in calculating the dust exposures in the present study of Factory A and it should be realised that they are different from those used in the 1968 BOHS study. Bearing in mind that considerable extrapolation was necessary and that conditions and processes in the factory are very different today, it will be realised that considerable uncertainty must be attached to such factors. (b) Factory B The Owens Jet dust counter was in use at Factory B in 1951 and continued to be used routinely until 1959. Up to 1956, the `ashed* coverslips were counted at a magnification of 900-1000 x and no differentiation was made between fibres and particles. After this date, the count was limited to particles of size greater than 1 urn and from January 1958 fibres longer than 5 pm were recorded as welL Between 1958 and 1961 the Long Running Thermal Precipitator (LRTP) was used on an experimental basis for comparison with the Owens Jet. After trials, the membrane filter sampler came into use in July 1961 and in June 1963 phase contrast was introduced, increasing the counts by a factor of about 1.6. The use of an eyepiece graticule m the form of a 7 mm Miller Square began in 1971 and this was replaced by a circular graticule, 6 mm in diameter, in 1974. In contrast with the experience of Factory A, no increase in fibres counted per unit area was observed as compared with counting full microscope fields. In addition to membrane filters, the Royco Instrument was widely used from 1963 ' onwards. With careful calibration of the instrument against membrane filter, the Royco can be more reliable than microscope counting. 0uS325 6 . iOI*SCttirmo?iAs5s?'H 4'e) Permml sampling Towards the end or the period covered by the study, from about 1974 onwards, `personal* sampling was used increasingly instead ofstatic methods, `Personal* means that the sampling head was attached to the lapel of an individual worker. As experience was gained, it became apparent that the results from personal samples did not generally equate with the results from static samples in the same working area, even for samples taken simultaneously. The Committee therefore made a study of the information available in this held, as detailed in Appendix 2B, and came to the following conclusions: (i) When identical sampling instruments are deployed simultaneously at personal and static sampling points and the distances between them are reasonably small, most of the personal sampling results obtained in a given location are higher than those obtained from static sampling. (ii) The differences between the two types of result tend to be particularly great when the static sampling points are relatively remote from dust emission points, for example, when background static sampling is adopted. (iii) In certain cases results from personal sampling may be lower than those from static sampling, owing to factors such as the positioning of the static sampling point with respect to air extraction systems. (iv) The correlation coefficient between personal and static measurements is statistically significant but, even so, no consistent relationship of great practical utility could be found in the limited data available. In the light of the above, the Committee decided to use only the results from static samples in calculating exposures. 5 THE GROUPS STUDIED (a) Factory A Three hundred men* from Factory A met the criteria for inclusion in the study, but no medical records were available for five of them. The present study is therefore concerned with the remaining 295 men. It was recognised that the 10 yr restriction might have resulted in bias if many persons with less than 10 yr exposure had suffered adverse health effects because of such exposure. A random 5% sample was therefore taken of all those who had commenced work in the factory during the 26 yr covered by the study. This gave 850 names, but, when women and those who had never worked with asbestos were excluded, 487 men were left, 15 of whom had worked with asbestos for moie than 10 yr; 14 of these were in the study group, one having been inadvertently omitted in the original record search. Of the remaining 472, 71 % had less than 1 yr exposure up to the end of 1976 and only about 6% had worked for between 5 and 10 yr. Of 16 men who had left the factory for medical reasons, one had worked with asbestos for 3 yr and the remaining 15 had less than 1 yr exposure. The conclusion reached from this sampling exercise, therefore, was that it seemed unlikely that the criteria for admission to the study had excluded many who had adverse health effects arising from their exposure to asbestos dust at the factory. Men only. following (he pattern of earlier studies at this factory 0uS326 Health experience in two U.K. asbestoi factories 7 '-{b) Factory B - Although at least 499 persons from Factory B met the criteria for inclusion in the study, some had to be excluded because ofincomplete medical and radiological data. In the end. the 351 persons for whom two serial chest radiographs were available were considered, comprising 323 men and 28 women. Information was provided for 3361 persons who had been exposed since January 1951 but for less than 10 yr. The distribution of exposure periods in these groups was different from that of Factory A, 22 % having w orked with asbestos for less than 1 yr, as against 71 % for Factory A, and 72% for 1-5 yr, as against 22% for Factory A. There was also a considerable contrast between the factories in the sub-groups who had left asbestos areas on medical advice. In Factory B, of 171 such persons, 106 (62%) had only worked with asbestos for from i to 5 yr. One very laudable reason for this was that in Factory B a number of people were advised to leave asbestos areas in the early 1960s on the appearance ofearly suggestive signs of lung fibrosis. Some 70 people were removed from exposure between 1963 and 1965 because of adverse lung function results. Many more were recommended for transfer to non-dusty departments. They included persons with bronchitis, old TB scarring, kyphoscoliosis and persistent cough. The survivors of the 70 or so removed because of lung function abnormalities are being followed up by the company. The main reason for their exclusion from the BOHS study was that the early dust records associated with these people were not acceptable as being valid for that purpose. Nevertheless, these people were lost to the study, although some may have developed abnormalities as a result of their exposure to asbestos dust. It is also possible that some had completed more than 10 yr exposure at the time of withdrawal. 6 THE RADIOLOGICAL DATA-FACTORY A AND FACTORY B The earliest (post-1950) and latest (pre-1977) chest radiographs for the 295 men from Factory A and the 351 persons from Factory B were made available for the study. In addition, 160 chest radiographs from 160 persons employed at the factories, but with no known direct exposure to asbestos, were also provided. These, together with the 1292 films from the exposed groups, were pooled and arranged in random order before presentation to the readers. 7 THE CLINICAL DATA (a) Factory A Available lung function and anthropometric measurements, information on smoking habits and records of w hether or not chest sounds had been heard were taken from the medical records of the 295 men. There were no lung function data available for 56 of them, but all of these had attended for medical examination at least once during the stud> period. At least two sets of lung function measurements were available for 184 men in this group. (b) Factory B Similar information to the above was made available for the 351 persons in this group. No lung function data were available for 38 of them. The records indicating the 00S327 I ' IBW* : presence nr absence ofchest' sounds at the iates! medical examination were included for study, but earlier assessments of whether this condition had or had not occurred were not studied, 8. THE DUST EXPOSURE DATA fa) Factory A By using the approximate relationships described in Paragraph 4(a) the records of measured dust levels in the factory were converted to modern membrane filler values for the various job locations. Using these values and thejob histories ofthe individuals in the cohort, estimates of exposure for each year employed were derived, expressed as fibre-yr/ml, assuming static sampling only. No attempt was made to convert to personal sampling because of the uncertainties attending such conversion [see Paragraph 4(c) and Appendix 2]. Even ignoring any reservations concerning the accuracy of the conversion factors themselves, the estimates of personal exposure could not be precise, as annual average values from static measurements had to be employed and in some cases further assumptions had to be made because job histories were not complete. (b) Factory B I.iformation was available on the time worked by the persons concerned at the various factory locations and measurements of dust concentrations at some, but by no means all, of these locations were also available. However, taking into account also the uncertainties about the fibre concentration in the 1950s, a close examination showed that the information available might provide reasonably reliable estimates of cumulative dust exposure for only 16% of the group. As will be seen, this put some restriction on the analysis of the Factory B data. 9. ANALYSIS OF THE DATA (a) Radiological results (i) Parenchymal abnormalities. The distributions of film classifications by factory, reader and type of opacity for both the earlier and later films of the pairs revealed systematic differences between the three readers in their interpretation of the distinction between small rounded and small irregular opacities. Less variability was found for `combined opacities' and this parameter was therefore used in the analysis. One deviation from the general pattern was the relatively frequent assessment of abnormality by Reader 3 among" the later films from Factory B. Overall, however, parenchyma! abnormalities were noted in a higher proportion of the Factory A group than for Factory B (ii) Pleural abnormalities. Taking an average of the observations of the three readers, 4.4% of the films early and late showed obliteration of the costophrenic angle, 2 1% showed pleural thickening and 0.4% pleural calcification More abnormalities were seen on films from Factory A than from Factory B, but ii is noteworthy that the differences between readers were larger than the differences between factories. In 0u8328 Health experience in two U K. asbestos factories neither case were the results distinguishable statistically from assessments of control films. (iii) Technical quality ofradiographs. There were large differences between readers in their judgement of the quality of the radiographs, but all three were less satisfied with the films from Factory A than with those from Factory B. That the more frequent assessment of parenchymal change in the Factory A films was not due to this cause alone was confirmed by assessing separately a sub-group of film pairs of good quality. These variations in film quality did not affect the pattern of assessment of pleural abnormalities. (iv) Smalt opacities and smoking habits. All readers detected small opacities more frequently , in Factory A among smokers and ex-smokers than among non-smokers (about 11 % higher). Nevertheless, small opacities were also detected on about 12% of the non-smokers' films, indicating that the changes seen in the later films were not wholly attributable to smoking. No such information could be gleaned from the Factory B films, because Readers 1 and 2 judged only a marginally higher proportion of combined opacities in the later films than in the controls. It should be noted, however, that Reader 3 classified 18% of these films into category 0/1 or higher, compared with 6% of the controls. (b) Radiological changes and dust exposure (i) Factory A. An effort was made to relate profusion of combined small opacities with cumulated dust exposure, and for this purpose four measures of exposure were examined for each individual. The first (t) was the cumulative exposure from commencing work in asbestos areas up to the time ofthe earlier of the two films and the second (Eh) was the exposure incurred between films. The third measure (Ee) was the cumulative exposure from commencement up to the later film, i.e. , + Eb. The fourth measure (d) was an attempt to approximate the exposure up to the point when the observed change occurred and was taken to be ,+ $(*}. No association could be found between radiological change and , or Eb separately. Both e and d were associated with increasing profusion of small opacities on the radiographs studied. fit) Factory B As noted in Paragraph 8(b), the variety of methods by which the dust measurements had been made at Factory B, together with the number of changes in materials, conditions and processes at the factory which had occurred over the period of the study, ruled out any attempt to estimate cumulative dust exposures for individuals. However, reliable information on time worked over the period of the studv was available for 187 persons who had definitely worked previously in occupations with potential exposure to dust other than asbestos and for 128 persons with no such prior exposure. An assessment was made of changes in profusion of combined small opacities for both of these sub-groups, related to time in years spent working with asbestos. Readers 1 and 3 recorded more radiological change between pairs of films for persons with longer periods ot exposure to asbestos, but Reader 2 did not show this trend. 0uS329 to *OHS - - ' ".f. ' (c) Lung function changes and dust exposure _' \i) Factory d. Of the 295 men in the group, one set ofJung function measurements was available for 239 and two sets or more for 134 ef them. An attempt was made to t correlate the latest measurement recorded with the cumulative dust exposure up to that time, using a linear multiple regression mode! to take account ofage, height, weight and smoking habits. The lung function criteria considered were FE\FVC, Tico and the ratio FEVJFVC. Only for FEV{ and FVC did the dust exposures correlate significantly it the 6% level; neither with Tlco nor with FEVxjFVC was any correlation observed. (ii) Factory B. Despite the difficulty associated with the dust data, the information from Factory B was examined further in the hope that it might be possible to proceed to a case-control study. This analysis had to be abandoned, unfortunately, because the sub-set of data that might be suitable for detailed study was biased epidemiologicafly, as explained earlier [Paragraph 5(b)]. 10. THE CRITERIA FOR "ADVERSE EFFECT' Further analyses were made in response to advice from medical members of the Sub-committee on what should constitute the earliest medical indication of adverse effects on the lungs whether through exposure to asbestos dust or otherwise (Appendix 1). Despite certain difficulties in applying these recommendations, seven statistical criteria were defined. Six of them reflect approximately some of the suggestions from the Medical Working Group. The seventh (rate ofreduction in FEVt) was included, because earlier analyses indicated that this measure oflung function was more closely related to the dust exposure data than the other indices offunction under consideration. The seven criteria included two radiological criteria (parenchymal changes and pleural shadowing), four lung function criteria and one of basal rales (as used in the 1968 study). It must be remembered that none of these criteria is specific to asbestos exposure. 11. THE OCCURRENCE OF ADVERSE EFFECTS The criteria employed were as follows: A At least two leaders agreed that there were two or more steps of change on the profusion scale for combined small opacities over the interval between films. B At least two readers agreed that a pleural abnormality w as present on the later but not on the earlier film of a pair (where 'pleural abnormality' means at least one of pleural thickening, pleura! calcification, or costophrenic angle obliteration). C Unusual* rate of change in FEVX. D Unusual* rate of change in FVC. E Unusual* rate of change in Tlco. F Any one measurement of FEVJFVC<0.70. G Chest sounds which did not dear on coughing or on any subsequent examinations. `Unusual* defined in terms of distribution of residuals, see Appendix J. Paragraphs 54-56 0'jS330 Health experience in two UK. asbestos factories il Z For effects A-E the relevant exposures were assumed to be those accumulated half way between the `early' and late* examinations. Effect F accounted for 40% of all effect-occurrences in Factory A and 34% of all dTcct-occurrences in Factory B. It did not correlate with exposure (in Factory A) and this bears out ihe latest thinking that FEVJFVC <0.70 is an inappropriate criterion of an adverse effect of asbestos. It is well known, for example, that smokers develop a reduced FEVJFVC (Cotes, 1975; Parkes, 1982) and there were many smokers in the populations studied. (a) Factory A Of the 295 men in the group, the results from 163 of them met one or more of the seven criteria. The total number ofoccurrences was 274. The most frequently occurring effect was F (FEVJFVC<0.70), being present in II1 men, and in 52 of them it was accompanied by at least one of the other categories of adverse effect. Among the 163 men who met at least one of the criteria the distribution of those with one, with two and with three or more effects was 58, 26 and 16% respectively. (b) Factory B Of the 351 persons in the group, the results from 163 (154 men, 9 women) met one or more of the seven criteria. The total number of occurrences was 257. As in Factory A, the most frequently occurring effect was F, being present in 88 members of the group. Because there were fewer radiological changes recorded for Factory B, there was a smaller number with effects A and B, but among persons with at least one recording of an adverse effect the distribution of those with one, with two and with three or more was similar to that from Factory A, being 66, 19 and 15% respectively. 12. INTERPRETATION OF THE DATA ON ADVERSE EFFECTS This was possible only for Factory A, for which cumulative dust exposures were available. The probability of the occurrence of an adverse effect before the corresponding dust exposure had been accumulated was estimated using the `Product Limit' (or `Life-Table*) method. The probability-exposure results were plotted on lcgisttc-lcg scales and the patterns for adverse effects A, B, D, E, F and G are shown in Figs. 4, 6-10 of Appendix 3. The results are summarised in Fig. 11 in the form of a plot of estimated probabilities that at least one of the seven adverse effects may occur by the exposure shown When mere than one effect was present in the same man, that occurring earliest was used, it will be seen that five persons showed an adverse effect at exposures less than 25 fibre-yr/ml. In two cases the effect concerned was E (unusual rate of change in Gas Transfer Factor) with one each for C (unusual rate of change in fKj), F (FEVJFVC <0.70) and G (chest sounds). At first sight, the graphs suggest that it might be appropriate to fit straight lines to the individual observations, thus postulating a logistic model for the various adverse effect-exposure relationships, but the deviations below about iOO fibre-yr/ml (50 fibre-yr/ml by 1968 standards) argue against this. It would therefore be unwise to use such fitted lines to make predictions where exposures have been below this level. 0uS331 12 SOUS Committee m Asamm 13. CONCLUSIONS (i) As far as Factory A is concerned, it appears unlikely that the criteria for admission to the study (not less than 10 yr exposure) excluded many who had suffered serious health effects arising from their exposure. (jj) The data from Factory B must be regarded as biased for epidemiological purposes, because the medical care policy was to remove persons'from exposure whenever examination indicated early signs of lung function abnormality These persons were not incii: fed in the study of Factory B, yet some of them may have developed the signs as a result of their exposure to asbestos. (iii) The radiological results for Factory A showed an association between the occurrence of parenchymal changes and estimates of cumulative exposure to asbestos dust up to the approximate point in lime at which the changes were likely to have occurred. Although it was not possible to estimate cumulative dust exposures for most persons from Factory 3, there was some evidence that longer periods ofexposure were associated with higher chances of developing small opacities on chest radiographs. (iv) Small opacities were delected more frequently among smokers and ex smokers, but the parenchymal changes observed in the group could not be attributed wholly to smoking habits. (v) Overall, the three readers judged 5.3% of films from Factory A and 3.8% of those from Factory B as showing obliteration cf the costophrenic angle, results which were not significantly different from observations on the 160 radiographs of persons who had not been exposed to asbestos. The same was true of other pleural abnoiTnalities which were recorded even less frequently. (vij Standardized levels of FEVl and FVC among men who had accumulated relatively high exposures in Factory A were lower than the levels among those who had received only low exposures and the correlations with dust exposure were s;atisticaily significant at the 6% level. An> such apparent correlations with Gas Transfer Facto, and with FEVlfFVC could easily have arisen by chance in view of the residual variability in the data. (vii) The study period was limited to the years over which it was believed consistent estimates could be made of dust exposure when assessed by static monitoring. Technical investigations were undertaken which clarified the relationships between the various methods employe^ for sampling and counting, even though much uncertainty remains. The analysis was limited to estimates of grouped time-weighted average exposures over the penod of study It was not possible to allow for the variation in exposure between one worker and another doing the same job nor fo: the inevitable fluctuations in exoosure between one day and the next. Finally, it should be noted that the Committee concluded it was not feasible to convert the estimates from static monitoring into measurements that would have been obtained b> personal monitoring (viii | The results from Factors A suggest that, for cumulative exposures based on static sampling [sec P?.agraph 4(c)] up to about 25 fibre-yr/ml, the probability that any one of the seven defined events occurred is less than 2% For exposures less than 50 fibre-yr/ml, the estimated probability is less than 7% and for exposures up to 100 fibrtyr/ml the probability increases ,o 17-20%. It must be recognised, however, that the statistical definitions of the events concerned arc based broadly on guidelines suggested 0u3332 1 Health experience in two U.K. asbestos factories O ."1 Hby the Committee's Medical Working Group regarding `the earliest index that the chest ` of a worker was adversely affected, whether through exposure to asbestot dust or otherwise'; they do not constitute clinical diagnoses of asbestos-related disease. Furthermore, these probabilities are based on the assumption that the adverse effects A-E occurred at exposures accumulated half-way between the earliest and latest medical examinations. fix) One of the criteria of adverse effect, namely FEVJFVC< 0.70, accounted for 40% of all effect-occurrences in Factory A and 34% of all effect-occurrences in Factory B. It did not correlate with exposure and this bears out the latest thinking that FEVJFVC <0.70 is an inappropriate criterion of an adverse effect of asbestos. Acknon-Udgtmmts--The Committee wishes to record its thanks to thosewho assisted in the compiatioa of this Report as follows: (a) The Asbestos industry for providing the medical and dust exposure data; (b) Mr R. Clayton and Mr J. R Hoyes for providing Appendix 2; (c) Dr L H. Cape!. Dr i. A. Dick and Dr I. C. Gilson tor dttst&ihf thechest radiographs; (d)DrM. Jacobsen for carryingout the analysis ofthedataas detailed in Appendix 3, and the Directorof the Institute of Occupational Medicine, Edinburgh, for providing the facilities. The Chair man wishes to record hisspecial thanks to all the members,ofthe Committee who. over several years and under very trying circumstances, freeiy.gtve their time Thanksjo also to the offieereofthe Society and its Council members for their sdvice and help in thehnal Sages. ltspiicalar,tbe E<^or-tn-luef:jiisycd an important part in smoothing the passage ofthis report through its pce-pubUcation stage; Finally, thanks go to the ordinary members of the Society for their understanding and patience. REFERENCES AssrsTosis Research Council (19? 1) The measurement of airborne asbestos dust by the membrane fiber method. Technical note 1." Revised September 1971. The Asbestosb Research Council, Rochdale. - Beckett. S. T, Hey, R.K. Hirst. RvHunt, It D., Jarvis, JL. and Rickards, A. L. (1976)A comparisoo of airborne asbestos fibre counting.with and without an eyepiece graticule. Am. occup. Hyg. 19,49-76. Berry. G, Gilson, i. C, Holmes. S, Lewinsomn, H. C and Roach. S. A (1979). Aibestosis; t study, of dose-response reiaiionships is an asbestos textile factory. Br. J. mi. Mti. $&, 98^112. British Occupational HygieneSocKrv:COMMHmcmHygenzStandards (1968) Am. occup. Hyp. 11, 47-49. BS 3625 (1963) Eyepiece and screen graticules .for tbedetcnranatioa of partide size of powders. British Standards Institution. Cotes. 1. E. (1975) Lung Function. Blackwell Scientific, London. Health and Safety Commission (1979) Asbestos: Final report of the Advisory Committee, Vols I and II. HMSO. London. International Labour Office (1972) ILO U/C Internationa! Classification r Radiographs of the Pneumoconioses (1971). Occupational Safety and "Health Senes No. 22 (revised). ILO. Geneva. Parses. W. R (1982) Occupational Lung Disorders. Buttcrwonhs, London. Peto. J_ Doll. R- Howard, S. V, Kinlen, L J. and Lewinsomn, H. C (1977) A mortality study among workers in an English asbestos factory. Br. J. Ini. Med. 34, 169-173. The Asiutos Regulations, SI No. 690.1969. HMSO. Walton. W H (1982) The nature, hazards and assessment of occupational exposure to airborne asbestos dusr a review. Ann. occup. Hyg. 25, 117-247. GDS333 APPENDIX 1 REPORT OF THE MEDICAL WORKING GROUP MEMBERS Dr W. J. Smither, Dr L. H. Capel. Dr W. H. A. BEVERLEY,-Dr 3. G. Mch *is TERMS OF REFERENCE The medical working group was asked to advise on the first medical indication or indications of adverse effects on the lungs and to make recommendations. DELIBERATIONS The group re-emphasized the importance of the principle of using the records of each employee in such a way that he may act as his own biological monitor, to detect the earliest signs of adverse effects of asbestos dust exposure. This principle involves comparing a worker's clinical, radiological, and pulmonary functional findings at the time of examination with those obtained at previous examinations, especially at the initial or pre-employment examination. Deviations from the man's own norm determined by previous examinations and tests are more significant than deviations from the `average* or `general population* normal. Any such deviations that cannot be attributed to secular changes require careful consideration even in the absence of recognisable disease, disorder or disability. It is impossible to use a simple test to detect the adverse effects of inhalation of asbestos dust such as the Mantoux test for tuberculosis. No such test exists. In considering the role of`crackles, crepitations or rales* the working party agreed that these had been inadequately defined or described in the past [See Conclusions, Paragraph (ix). Section 1]. Many other conditions can cause added sounds such as crackles at the lung bases, and even those crackles characteristic of interstitial pulmonary fibrosis in liming and persistence are not unique to asbestosis. For those reasons their significance may have been over-emphasized in past surveys. Just as the presence of crackles is not diagnostic of asbestosis, so radiological changes in themselves are not necessarily caused by asbestos dust exposure. The working group discussed fully the value of lung function tests. Assessment of Forced Expiratory Volume (FEV) as a proportion of Forced Vital Capacity (FVC\ or Vital Capacity (VC) can help in the recognition of airways narrowing from whatever cause. If pulmonary asbestosis is the only lung disorder to be considered in any ore case, the Ga< Transfer Factor of the lung (Tlco) does not necessarily give more information than serially recorded changes in VC. Moreover, Tlco is more variable. If other lung disorders are present, such as emphysema, then the Gas Transfer Factor per unit of lung volume (Kco) may help in differential diagnosis. For example, Kco will drop in emphysema. 14 0u3334 Health experience in two U.K. asbestos factories--AppentSx 1 'J 15 .~i The working group felt that the change and the rate of change in VC are probably the most practically useful measurements in assessing the development of lung function change due to exposure to asbestos dust. The degree and rate ofchange depend for their determination on comparison with the worker's initial assessment. In all these matters the working party concerned itself with the diagnostic and epidemiological importance of early detection of an adverse effect rather than medico legal or prognostic aspects. They recognised the difference between evidence of the earliest signs of adverse effect possibly due to asbestos dust exposure and evidence supporting a diagnosis of asbestosis. The presence of any physical, physiological or radiological finding which could be due to asbestos exposure requires further investigation before a diagnosis of early asbestosis can be made. The diagnosis of early asbestosis rests on experienced clinical judgement. There are no standardized criteria for the diagnosis of asbestosis. CONCLUSIONS (i) Adverse effects of asbestos dust inhalation arise from any structural, functional or serological change caused by it. Such change is not necessarily recognisable as of clinical or functional importance at the time of examination and is not likely to be the same in various affected persons. (ii) it is unlikely that any single criterion would uniquely provide the earliest warning of adverse effects in all individuals. (iti) The Sub-committee is concerned with the medical and epidemiological importance of detecting adverse effects, not with the medico-legal or statutory aspects of asbestos-related disease. (iv) Examination of the pattern of serial trends in the records of an employee's physical, functional, radiological and serological findings is likely to provide the earliest warning of adverse effects of exposure to inhalation of asbestos dust. (v) Any pattern ofchanges which cannot be attributed to ageing or to co-existing disorder should provisionally be attributed to the results of asbestos dust inhalation in exposed workers. (vi) An individual employee may belong to any one of the following: Group (a) Unaffected by asbestos dust exposure but ageing normally. Group (b) Unaffected by asbestos dust exposure but affected by other disorders. Group (c) Affected by asbestos dust exposure but not affected by other disorders. Group (d) Affected by both asbestos dust exposure and other disorders. (vii) For epidemiological purposes the distribution of these groups among all employees and the probability that an individual belongs to any particular group would best be determined by comparison with matched controls. (vii!) In the absence of such matched controls the groups and any individual assigned to a particular group might be identified as follows: Group (a) Having no clinical abnormality, and with functional and radiological findings within the normal range (and serological findings unchanged).* 4 Serologwai mminaiions have am tam regularly recorded! in luona is the past; in future ihit may become a man widespread practice. 0uS335 '-if ; : t* Group serdogicat finding! taken into K^^nt) refejr4^d- r* `ft' in cv*Mu<i^'ote sham tfetmof from eteiws dust expoisire. Group (c) Having k pattern ofelfhieaf, rtdtoldgkai and funcaionalchsnfes {with, serological findings taken into account) showing one or more abnormalities in any one or more of these parameters. Group (d) Having a pattern of changes as defined in both (b)and (c) above* (ix) The important criteria for recognition of the adverse effects of exposure to asbestos dust can include the following: (1) Clinical findings. The development of end-inspiratory crackles. These are interrupted sounds occurring towards the end of a Jong, slow inspiration following a complete expiration. They do not clear with coughing or on any subsequent examination and are likely to persist throughout life. The possibility that wheeze is also important is not excluded, particularly when wheeze and crackles occur together. Clubbing of the fingers, breathlessness and cyanosis are very late findings and by no means unique to the adverse effects ofasbestos dust inhalation. (2) Radiological features. Any parenchymal or pleural change, excluding those due to conditions other than exposure to asbestos dust. (3) Lung function changes, (a) A fall in the Vital Capacity greater than that to be expected from ageing. (b) A fall in the Single Breath Gas Transfer Factor greater than expected from ageing. It is considered that any such fall would parallel a fall in the Vital Capacity. The Gas Transfer Coefficient (Kco) may prove helpful in differential diagnosis, especially in the recognition of alveolar damage from inflation and loss of alveolar walk (as in emphysema) when the value of both Coefficient and Factor will fall. (4) Serological investigations. Antinuclear, rheumatoid and HLA factors should be taken into account. It seems probable that changes in the first two of these will parallel changes in other features. Any other diagnostic use and the importance of any other serological changes remain to be discovered. (x) If there were a control population matched for age, sex, cigarette smoking and climatic exposure in which occupational exposure to asbestos dust has been excluded, then the incidence and prevalence of the adverse effects of asbestos dust inhalation in a test population could be assessed and used in the judgement of any dust exposure standard. (xi) In the individua. case, recognition of the presence of adverse effects of exposure to asbestos dust inhalation is a judgement of probability. * The evaluation of these changes would need to be based on the opinion ot a group of observers of wide clinical experience able to judge the balance of probabilities 0u3336 Health experience in two U.K. asbestos factories--Appendix i J 17 RECOMMENDATIONS The members of the Working Group agreed that, solelyfor the purpose ofthis study, the eariiest index that the lungs of a worker were adversely affected, whether through exposure to asbestos dust or otherwise, excluding early tuberculosis, would include the first appearance of one or more of the following: (i) Late inspiratory crackles m the lower third of the thorax which do not clear on coughing or on any subsequent examination. (ii) Radiological pleural shadowing {with or without calcification). (iii) Radiological parenchymal changes in the lower half of the lung fields. (iv) Vital Capacity more than 20% below the predicted value, with the FEVJFVC remaining o- ^r 0.70. (v) Vital Capacity falling faster than predicted by 20% or more without concomitant increases in the Functional Residual Capacity. (vi) Single Breath Gas Transfer Factor 20% or more below the predicted value. (vii) Gas Transfer Factor falling faster than predicted by 20% or more. (viii) FEVJFVC less than 0.70. it is recognised that the commonest cause of obstructive lung disease as measured by diminution in FEVJFVC is cigarette smoking (Parkes, 1982). It is possible that there are adverse effects of asbestos dust inhalation if one of the above eight adverse affects is present; the possibility increases with the presence of additional factors and with increasing magnitude of the abnormality in each factor. A scoring of probability should be taken into account when other conditions which might cause the abnormalities are deemed to be present in addition. REFERENCE Parks. W. R. (1982) Occupational Lung Disorders (2nd edn). Butterworths, London. 0u3337 DUST MEASUREMENTS SECTION A. WORK CARRIED OUT TO PRODUCE A CUMULATIVE EXPOSURE HISTORY FOR THE COHORT AT FACTORY A INTRODUCTION Owing to developments in instrumentation and methods of measurement, allied with a better understanding of occupational hygiene practices, present-day air sampling and sample evaluation techniques differ considerably from those used during She period from 1951 to 1964. In order to obtain a better understanding ofthe cumulative asbestos'dust exposure of the members of the Factory A cohort by static sampling, taking into consideration she various changes in methodology, a re-appraisal has been made of the available past dust data. Comparisons have been made between the results obtained from the different sampling and measuring methods used in the past with the present-day methods. Persona! sampling is discussed in Section B below. The historical development of these techniques at Factory A is summarized below and further illustrated by the calendar of events in Fig. 1. (a) Casella Thermal Precipitator 1952-1960 The first quantitative measurements were carried out from 1952 to 1960, using the Casella Thermal Precipitator (TP) as a static monitoring device. Samples were obtained on glass slides which, after incineration, were examined under dark-ground illumination at 800-1000 x magnification. All particles >0.5 pm were counted, not just fibres. The results were expressed as partides/ntl. (b) Long Running Thermal Precipitator 1960-1964 The Long Running Thermal Precipitator was used between 1960 and 1964, with static monitoring. The sample was collected over a 0.5 in. square on a glass slide and fibres were counted using 500 x total magnification and light-ground microscopy. Results were expressed as fibres/ml but with no detailed knowledge of the standard error, which can be assumed to have been high. (c) Static membrane filter and Royco 1964-1974 Between 1964 and 1974 static sampling was carried out with membrane filter techniques and by means of a Royco particle counter calibrated to five equivalent membrane filter results. Membrane filter samples were evaluated at about 500 x magnification under phase contrast conditions, utilizing the full field of view . Results were expressed as fibres/ml. Although no proper understanding of the standard error was established at the time, the standard error for this form of estimation must have been greater than the 40% experienced with the modern procedure. (d) Personal membrane filler 1974 to present day The samples after collection are analysed by a team specially trained to carry out 18 0uS338 Health experience in two U.K. asbestos factories-- Appendix 2 0u3339 JjL M SI St. si ffce-Kwl PrtrifataftB ju * PattiOn/ml (US 2Uml ! ' i 60 61 62 6J 64 Otwnj Mrs* itmiin| llenml Fittfiliia Him F&retfml |S- HMfsnel. 6S 66 6? I 66 69 111 71 72 73 Mtmbrsnt fillet Suik PtftOftirf " M 4 l^.JZZZLJr.Z "Z~Z,ZVZZ / /' / "/ ~Z"Z7: Ku^cc PmIkI* Ceumti Smite {10 emu; IZZZ1__y_ 1 v Royco(IOmtn) Fihiet/ml (l-lgaura) itc>6 bmil rs/ Penes*! {I Hr) / 2zzzzzzzzzzi OSisnl---------- 3 on Vfptt il tMMI cy.zz / z-71 r v / ?->-> -r -r-7-v--r PtMteMltnl (}4|i| Fig 1. Historical development of measurement techniques at Factory A. '' . the micr<sssoip%' ':fifere gating prooxirc *rfed JftVg_' Council Tectmfeir Note ! (1971). TWs pfdorfure ` ii^!j|ar;;iMi'.i , meaningful number of fibres greater than S ftsu in length atffitets than 1/tm dm.-are observed through a phase contrast light microscope using a 40 x. objeciive.giraig m overall magnification of 600 x. Present-day fibre counting is carried out firing a standard eyepiece graticule (BS3625, 1963) in contrast to earlier fibre counting procedures which related to full field of view observations. Results from this type of analysis are recorded as fibres/ml and are known to have a standard error of 40% of the mean from monthly observations of performance of the counting team. CORRELATION EXERCISE 1977 It is clear from the preceding history that some way of interrelating the data from the different measurement procedures was needed ifcumulative exposure histories were to be constructed. Fortunately, it was possible to assemble the various pieces of equipment used during the past and to obtain the direct involvement of a person who was involved in the past monitoring programmes. Consequently, correlations have been studied between the different measuring procedures. In all instances, conversion factors have been derived to relate past data to modem membrane filter procedures, expressed as fibres/ml. It is important, however, to appreciate that standard errors cannot be quoted for the conversion of past data without a full knowledge of all the errors associated with the original data. Static membrane filter method In order to convert the `old' membrane filter and Royco results to present day values a conversion factor of times 2.0 as derived by Beckett et al. (1976) has been used to allow for the `graticule effect'. Ottway Long Running Thermal Precipitator (LRTP) A series of samples from the LRTP has been obtained and the results compared with data obtained from membrane filler samples obtained at the same time and from the same location. The LRTP values were obtained, as originally, in fibres/ml. There are many reservations about the precision of the comparison, not least of which is that factory conditions during 1977 are quite different from those of the past The levels of fibres observed in 1977 were much lower than those recorded in the 1950s and 1960s, resulting in an extrapolation of the fitted line well beyond the range of the current experimental observations. Bearing this aspect in mind along with the approximate nature of the actual experimental data, the regression line has been used to derive an approximate conversion of LRTP data to modern membrane filter values. The correlation plot along with the mean line and its extrapolation are illustrated in Fig. 2(a). The derived conversion factor was such that 2.2 times the LRTP value is roughly equivalent to a modern membrane filter result in fibres/ml. Casella Thermal Precipitator (TP) A comparison similar to that for the LRTP has been carried out for the TP. Similar reservations about the subsequent correlation must be made and several other factors must also be considered. It is of prime importance to remember that TP results were 0u3340 Health experience in two U.K.. asbestos factories--Appendix 2 21 Thermal Preeipitoter, portleles^OS jim/mt Ftci 2(a) and (bf Relationships between membrane filter (fibres/ml) and (a) Long Running Thermal Precipitator (fibres;ml), (b) Thermal Precipitator (partidcs/ml). The boxes near the origin indicate the ranges of concentrations measured in the comparison trials, while the full figures indicate the ranges ofextrapolation to earlier concentration levels. expressed as partides/ml and not fibres/ml. Enterljne (1976) draws attention to the uncertainties of obtaining correlation between particle counts obtained by the tmpinger sample collection device and membrane filter fibre counts, which further substantiates the need for caution in interpreting these early data. A further minor confusion was introduced by some of tbe TP samples bang 'contaminated' by a bloom forming on glass collecting slides. This bloom gave rise to exaggerated particlecounts. However, subsequent repeat samples at the samelocations. " ^ "' ;5:"' ##Hreb#^ . gave lower value thin those hut obtlne4t |^*y'^|^h*;tfw hloomle^eet. The interference ofTF samples by bloom was t wdlfikuoiw'Q f^tare;dfthti instrument when it was in use. The fitted fine for the TP data-is given in Fig,.2(b),.Again, extrapolation has bees necessary well beyond the range of the experimental data. The conversion factor derived from the graph is that a modern membrane filter value if approximately 0.07 times the result from the TP sample. This is, of course, different Jrom the conversion factors employed in the 1968 BOHS study which referred to membrane filter counting as conducted in 1961. ' CUMULATIVE DUST DATA By using the approximate relationships described above, the records of measured dust levels in the factory have been converted to modern membrane filter values for the various job locations. Using these relationships the job histories of the individuals in the cohort have been related to dust exposures. Personal histories have been constructed with a `static' dust exposure value for each separate year employed within the specified period of the cohort, resulting in a cumulative exposure. Clearly, the estimated exposure is not precise. Apart from the reservations about TP, LRTP and membrane filter correlations the number of approximations is large, not least of which is that annual average values from static measurements are assessed to be the actual individual exposures. The relationship between static and personal monitoring results is discussed in Section B. Also, some of the job histories were not quite complete and further assumptions had to be made to fill in the gaps. SECTION B. A COMPARISON OF FIBRE CONCENTRATIONS DETERMINED FROM PERSONAL SAMPLING AND STATIC SAMPLING INTRODUCTION Personal sampling involves attaching a membrane filter sampling head to the lapel of the person under test. Before the advent of personal sampling, asbestos dust concentrations were determined with static sampling techniques. Consequently, much of the historical information about asbestos dust concentrations, including that considered by previous BOHS Sub-Committees, refers to static sampling. In order to translate static sampling into values that would have been obtained had personal sampling been adopted, a knowledge of the relationship, if any, between personal and static sampling is required. In this section results from personal and static sampling surveys submitted by Committee members are presented in graphical form and some tentative conclusions are drawn about the relationship between the two types of data. SOURCES OF DATA (a) Factory a Three sets of data from Factory A were presented. The first was from personal and static samples in the same work areas although they were not obtained simultaneously 0u3342 Health experience in two U.K. ubetict factories--Appendix 2 3 23 m I w t- ;os. 3(a). (b) and (c). Personal vs static sampling results from Factory A. (a) First set of data. Samples not obtained simultaneously, (b) Second set. Each point represents mean of five 20 min static samples covering 3 hr personal sample on operative nearest (1-3 m) to static site, (c) Third set. Simultaneous static samples and operatives' personal samples at various machines. Each personal and static result is the mean from two samples (4 in one case). [Fig. 3(a)], fhe pump flow rate for the static sampling was twice that for the personal sampling. The second set, shown in Fig. 3(b), refers to simultaneous personal and static results over a representative range of operations. For this second set, five 20 min static samples were taken over the 3 hr period during which personal samples were being collected in the vicinity. The distance from the static sampling position to the nearest personal sampler depended upon the nature of the work but was generally between 1 an-* 3 m. The pump flow rate for the static sampling was four times that for the personal sampling. The third set ofdata was obtained at Factory A during an investigation by the HSE into sampling and measurement errors. Personal samples were obtained from operatives tending certain machines and static samples were collected simultansousiy sd at those machines. Some personal results were also obtained when sampling during LSI shifts other than the ones during which the static samples were obtained. All the results ch are shown in Fig. 3(c). at to iai (b) Factory B An extensive set of results from textile processes at Factory B is shown in Fig. 4. ltd They are values obtained from 4 hr personal samples and 15 min static sampling Royco ng counts taken on the same day. The Royco readings are in terms of particles/ml, the ne machine being set to give results equivalent to fibres/ml for textile processes at the l<L factory. (c) Factory C These data consist cf 32 pairs of results from simultaneous persona! and static sampling undertaken during the sawing of Marinite board. The distance between the id personal sampling head and the static sampling location was between 1 and 2 m. The *> data are shown in Fig. 5. 6u3343 21 Sialic Royeo, fibres /ml Fig 4. Personal vs staiic sampling results from textile processes at Factory B. iPersonal. 4 hr MF samples Static, IS min Royeo counts taken on same day as personal samples. Fic. 5. Personal vs static sampling results from Factory C. Simultaneous sampling during sawing of Marinite hoard. Distance between instruments 1-2 m. 0'jS344 Health experience ta two U K. asbestos factories--Appendix 2 25 Ftc 6 Personal vs static sampling results from Factory D classified by asbestos type. Various operations; mostiv overlapping sampling periods; distances between instruments mostly in range 6-15 m. (d) Factory D This set refers to both chrysotiie and amosite and many different operations. There was generally some overlap of the sampling periods, although they were not strictly simultaneous. The distances between personal and static sampling locations were mostly in the range 6-15 m. the most extreme distance being 30 m. The results are shown in Fig. 6. DISCUSSION F cures 3-6 are plots of personal against static sampling results for data from difTerv.it sources. On each graph a demarcation line has been drawn between the 'personal greater than static' and the personal less than static' regions. In every case there is a tendency for the personal sample results to be greater than the static results. The relationship between personal and static sampling results obtained in a particular work area depends on; fi) the spatial distribution of dust concentrations in the area, which in turn depends on the nature of the dust emission sources, the work practices and ventilation arrangements; (H) ibe,Ix*tl6n of fhejtatic saiopll^ ' " (Si) ihe,opoiivc' position relative io&ttaffepoftMjnd bis pereonal-wciiiqt practices; - (iv) time factors, including the duration of sampUng with the two types of measurement, the frequency of sampling over a given lime period and whether or not the sampling is simultaneous; (v) inherent sampling and counting errors. ^ In the limit, where the operative wearing a personal sampler is stationary and standing next to a static sampling point, the two results obtained might be expected to differ least. However, where there are large distances between the personal and static sampling points and/or when there are large gradients in concentration and when the measurements are not simultaneous, the situation becomes increasingly more complex. The second and third set ofresults from Factory A, Figs 3(b) and (ck and the results from Factory C (Fig. 5) provide data on simultaneous sampling where the distances between the personal and static sampling sites were reasonably small. It can be seen that, although there is a great deal of variation in the personal sampling results corresponding to a given static sampling result, there is a marked tendency for the personal sampling results to be greater than those obtained from static sampling (49 out of 64). The sets ofdata for which the results are not strictly simultaneous, but for which the same type of sampling instrument was used for both variables, support the conclusion that there is a tendency for personal sampling results to be greater than those from static sampling. Indeed, in the data from Factory D (Fig. 6) nearly all the personal sampling results are higher than those obtained from static sampling. It is possible that this is due to this set ofdata including a higher proportion ofstatic sampling results that were obtained in more remote positions than those obtained at Factory A. (In some working locations, it is impractical to position a static sampler dose to a typical operative.) Discussions on past static sampling strategies between il.e staff concerned tend to support this possibility. The results from Factory B strongly support these findings, even though different types of instrument were employed for the personal and static sampling. CONCLUSIONS The relationship between static and personal sampling results varies according to the characteristics of the dust emission sources and the general and individual work practices adopted in a particular work area. The present study indicates that; (i) When identical sampling instruments are deployed simultaneously at personal and static sampling points and the distances between them are reasonably small, at least two-thirds of the personal sampling tesults obtained in a given working location are higher than those obtained from static sampling. (ii) The differences found between the two types of result tend to be particularly great where the static sampling points are relatively remote from dust emission points, as, for example, when `background' static testing is adopted fin) In certain cases, results from personal sampling may be lower than those from 0uS346 Health experience in two U K. asbestos factories--Appendix 2 n .1 - stake sampling, owing to factors such as the petitioning of the sampling point with : respect to air extraction systems. (iv) The correlation coefficient between the personal and static measurements is statistically significant, but, even so, no consistent relationship of great practical utility could be found in the limited data available. REFERENCES Asbestons Research Council (1971) The measurement of airborne asbestos dust by the membrane filter method Technical note 1. Revised September 1971. The Asbestosts Research Council Rocbdak. Beckett. S. T, Hex 1. K,, Hirst, R,, Hunt, R, D, Jarvis, J. L. and Rickards,A. L. (1976) A comparison of airborne asbestos fibre counting with and without an eyepiece graticule. Aim. oceupl Hyp: 19,69-76. Enterline, P. E. (1976) Pitfalls in epidemiological research. J. Occ. Med. 18, ISO-156. 0US347 AN ANALYSIS OF MEDICAL AND DUST EXPOSURE DATA FROM TWO asbestos factories REPORT TO THE BOHS COMMITTEE ON ASBESTOS FROMJ5R M JACOBSEN CONTENTS Introduction Definition of study groups Effect of excluding persons with less than 10 yr exposure at the factories The groups studied Available data Radiological results Correlation between lung function and dust exposure at Factory A `Adverse effects' Additional comments Summary and conclusions References Paragraph 1-2 3-4 3-15 16-19 20-26 27-42 43-45 46-74 75-81 82-94 INTRODUCTION (1) This report describes results from statistical analyses ofmaterial considered by the BOHS Committee on Asbestos during the period 1977-1979. The data are from two factories, A and B. (2) Earlier studies by the previous Sub-committee were based on related, but different, information from Factory A. The first report (BOHS, 1968) referred to a group of men who had worked at Factory A for 10 yr or more, whose exposures to asbestos had occurred only after 1 January 1933 and who were still employed at the factory on 30 June 1966. Berry et al. (1979) have described later results from the same factory, based on an extended group of men which included also those who completed 10 yr service between 30 June 1966 and 31 December 1972. DEFINITION OF STUDY GROUPS Factory A (3) The specification for inclusion in the study was, for Factory A: all men* who began work m `asbestos areas* in the factory after 31 December 1950. who had no known previous exposure to asbestos dust and who had completed at least 10 yr (not Men only, following the pattern of earlier studies at this factor) Health experience in two U.K. atbestos factories--Appendix 3 necessarily continuous) work with asbestos by 31 December 1976. This definition was designed to provide an administratively manageable number of persons for medical follow* up who had been exposed to asbestos only during a period when records ofdust concentrations at the factories were preserved. In this way it was hoped to reduce the uncertainties in estimating retrospectively cumulative exposures to dust. It was recognised, however, that the imposition of these criteria could lead to bias in the results if persons with less than 10 yr exposure (but who otherwise meet the definition) mduded many who had suffered adverse medical effects as a result oftheir exposure. An investigation was made therefore to assess approximately whether it is likely that such exclusions have influenced the findings. The results are reported below (Paragraphs 5-10). Factory B (4) Similar criteria were applied in an effort to arrange medical follow-up examinations for employees at Factory B. In this case women workers were also included. However, the data made available to the Sub-committee did not indude records from persons at Factory B who had been removed from exposure when dinical examinations indicated early signs of lung function abnormalities. In some cases such persons had been exposed for more than 10 yr. EFFECT OF EXCLUDING PERSONS WITH LESS THAN 10 YR EXPOSURE AT THE FACTORIES Factory A (5) An inspection of the Personnel Department's numbering system indicated that a total of 17 073 persons had joined the factory and might have worked with asbestos during the 26 yr period considered. It was not feasible to examine all these records individually and thus determine how many had been exposed to asbestos. A 5% random sample of the identification numbers was therefore selected. The relevant records were extracted from the files and summarized by staffin the company's Medical Department. (6) No records could be traced for 10 of the 850 numbers sampled. Seven men had worked with asbestos before 1951 and a further 150 had never worked with asbestos up to 31 December 1976. Ofthe numbers sampled, 196 referred to women employees. Thus the total number of men who had worked with asbestos in Factory A for the first time during the 26 yr is estimated to be of the order of 10000. (7) Table 1 shows the distribution of exposure times for the corresponding fraction of men sampled (487/850). Of 15 men who had been exposed for more than 10 yr. 14 are in the study-group; one had been omitted inadvertently when records were searched originally by factory medical staff to identify men meeting the criteria. (8) The sample results also indicated that 71% of the men who were not included m the study because they had worked less than 10 yr with asbestos had experienced less than i yr ofexposure up to the end of 1976. About 6% had worked between 5 and 10 yr with asbestos. If the arbi'rary 10 yr exposure period qualification for inclusion had been relaxed to, say, 8 yr, then this might have increased the number involved by about 200-400 (depending on how many of the 10 untraced records referred to men with at least 8 yr work with asbestos). j. - ? fewest T*mx i. Factory A; analysis or a tAmmmmM ncauacm^m* who m&mthmitm to nm Duration of exposure to asbestos W 10 or <1 1-5 5- 6- 7- 1- 9- more Total In study group Still working with asbestos 10 Ceased work at factory for medical reasons 15 Other leavers 313 AH men sampled with history of exposure to asbestos 338 15 1 90 106 3 8 1! 2 51 53 3 -l " ' 14 1 32 & 3 13 14 35 16 432 487 (9) One of the men sampled who left the factory for medical reasons had worked with asbestos for 3 yr; the other IS had less than ! yr exposure. It seems unlikely, therefore, that the criteria for admission to the study excluded many who had already suffered serious health effects arising from their exposure. However, Bbiry er a/. (1979) have reported that when the medical officer at Factory A considered that men were starting to develop symptoms or signs of early asbeslosis then they were advised to change to less dusty jobs. It is possible, therefore, that some of the men not eligible for study, because they had worked for less than 10 yr in asbestos areas, had demonstrated an early adverse effect of exposure. (10) Nearly 90% of the men sampled had left the factory before 1977 and most of these had experienced less than 5 yr exposure. (One of these men had died while still working with asbestos.) A rigorous medical follow-up of all such men from Factory A would have been impractical. Factory B (11) Table 2 shows the distribution of time worked with asbestos in Factory B for 3361 persons who were first exposed there after 1 January 1951 but who had not completed 10 yr exposure by 31 December 1976. The information was extracted by company staff from their files. (12) Of those excluded from the study because of failure to complete the 10 yr exposure period, 22% had worked with asbestos for less than 1 yr; 72% had been exposed for periods ranging from 1-5 yr; 6% had been exposed for at least 8 yr. This 1Tabu Factory B; duration of exposure to asbestos (yr) for 3361 persons noi qualifying for INCLUSION IN THE STUDY Duration of exposure to asbestos {yr t <1 1-5 5- 6- 7. 8- 9-10 Total Still working with asbestos 64 393 44 S3 94 74 27 Ceased work at factory for medical reasons 46 106 9 3 4 3 Other leavers 636 1399 137 97 71 54 47 All groups 746 898 190 153 169 128 77 749 171 2441 3361 G'j3350 Health experience in two U.K. asbestos factories--Appendix 3 31 indicates a different pattern from that in Factory A: the corresponding estimated figures there were 71, 22 and 6%, respectively. (13) The contrast between the factories in this respect is particularly noticeable for the sub-groups who had left the factory on medical advice. Of the 171 such.persons in Factory B, 106 (62%) had been exposed for at least one but less than 5 yr. A further 16 had been exposed for at least 5 yr; three of them for more than 9 yr. (14) Of those excluded from the Factory B study-group, 78% were no longer working there at the end of 1976. Some medical follow-up examinations have taken place in this sub-group, but this information has not been considered for the present study. (15) Of the 2441 persons no longer at Factory B on 31 December 3976,150 had died by that date. THE GROUPS STUDIED Factory A (16) From Factory A, 300 men met the criteria for inclusion in the study. No medical records were available for five of them. The remainder of this report is concerned therefore with 295 men. Of these, 137 were still employed at the factory on 31 December 1976; 130 had left; and 28 had died before that date. (All 295 men are included in the continuing mortality follow-up study by Peto el al, 1977.) f 17) Records of employment prior to joining the factory were examined for all 295 men. In 152 cases, there were references to jobs or industries which might have involved exposure to dusts or fumes, e.g. coal-mining, iron-mining, quarrying, foundry work, welding and cotton textiles. Complete previous employment records with no such references were available for only 6 men. The records for the other 137 men were incomplete in this respect and it is possible, therefore, that some of them may have been exposed to dust or fumes during periods not accounted for in their job histories. The age distributions of the two groups are shown in Table 3. Table 3. Percentage age distributions near middle of studv ferioo, according to available INFORMATION ON OCCUPATIONAL HISTORY BEFORE START OF STUDY PERIOD Exposure lo Age at t January 1965 No. of dust or fumes lyr) persons before 11 51 !9 20 25 30 35- 40- 45- SO- 55- 60- 65-70 in group Factor i A Yes Possibly tome All 0.1 3 5* 20 26 52.5 11.2 17 | 164 99 17,1 8.6 56 13 3 El 9 10 S 13 3 175 98 98 4 ! 129 n 5 139 14 9 IH 13 6 92 Factory 8 Yes No Possibly some 3l 6? n.s All 7.7 99 i; s 120 126 23 6 110 10.5 42 il 2 134 112 9.7 13.4 149 14.2 4.5 346 7.7 3.8 7.7 3.8 7.7 15.4 7,7 103 11.7 ; 514 108 88.5 81.7 82.3 4.0 3.3 4.2 37 1.6 0.7 0 t! * Includes six men with no exposure before t January 1951. 0.7 0.7 07 0 0 0 0 152 843* 295 19! 134 26 351 008351 ' i. 32 ... liS Factory B CIS) At tent 499 persons from Factory 1 met the criteria for inclusion in the study. The analyses reported here refer to 351 ofthem, for whom two serial chest radiographs were available. Of the 48 persons excluded because of incomplete medical data, 32 had died before 31 December 1976. (19) Of the 351 persons considered, 28 were women workers. There were 19 deaths among the 351 persons before 3! December 1976. At feast 191 (54%) of the study group had worked in jobs with potential exposure to dust or fumes prior tojoining the factory. Complete occupational history records (i.e. with no time-gaps) for 134 others (38%) showed no jobs in a dusty environment. Records for the remaining 26 were incomplete. These workers may have been exposed to some dust. The age distributions for the sub groups are also shown in Table 3. Those with some known prior exposure included a greater proportion in the middle age-groups and in this respect the age distributions from the two factories are similar. AVAILABLE DATA Radiological data (20) A large number ofchest radiographs were potentially available for study, since periodic medical examinations had taken place for exposed employees at both factories for many years. It was not possible to arrange for an epidemiologicaily valid re examination of all this material at the time (January 1978) when the Committee was endeavouring to supply to the HSC Advisory Committee on Asbestos a summary of the information which was then available to it. The Committee decided, therefore, to arrange for a controlled study of a limited number of the radiographs potentially available. (21) The earliest (post-1950) and latest (pre-1977) available chest radiographs for 295 men from Factory A and 351 persons from Factory B were considered. Individual dims from the 646 pairs were pooled and arranged in random order. Additionally, 160 chest radiographs from 160 persons employed at the factories, but with no known exposure to asbestos dust, were inserted randomly among the 1292 radiographs. (Each factory provided 80 of these 61ms.) The total of 1452 films were presented in turn to three physician? in February 1978. They were asked to classify them according to the 1LO U/C (1971) International Classification of Radiographs of Pneumoconioses. None of the three readers was aware of the inclusion of the 160 `control' films. This work was carried out over a period of 7 weeks early in 1978. An interim report on the results was communicated to the Medical Working Group of the HSC Advisory Committee on Asbestos in April 1978. Clinical data (22) Factory A. During the latter half of 1978, lung function and anthropometric measurements, information on smoking habits, and records of whether or not chest sounds had been heard were extracted from records of medical examinations by the medical staff at Factory A and made available to the sub-committee. The lung function measurements considered were Forced Expiratory Volume in 1 s (FE Vi}, Forced Vital Capacity (FVC) and Gas Transfer Factor (77co). There were no lung function data for 56 men from Factory A, but all had attended for medical examination at least once -C3* Health experience in two U.K.. asbestos factories--Appendix 3 33 during the study period. At least two sets of lung function measurements had been recorded during the 26 yr for 184 men. (23) Factory B. Similar information had been made available earlier for the 351 persons from Factory B. There were no Sung function data for 38 of them. The presence or absence of post-tussive chest sounds at the latest medicd examinations was recorded, but results from earlier assessments of whether this condition had occurred were not studied by the Sub-committee. Exposure to asbestos (24) Factory A. Manuscript sheets describing occupation, work area in the factory and relevant calendar dates were compiled by Factory A occupational hygiene staff for each man included in the study. Also shown were the corresponding annual averages of concentrations of asbestos dust at those work places during the calendar years concerned. The concentrations were expressed as fibres/ml of sampled air as determined from fibre counts on membrane filter samples by the counting method used at the factory since 1977 (Appendix 2). (25) Exposures to dust for portions of time in each work area were recorded on the same sheets, which were made available for the statistical analysis. The exposures were calculated as the sum of the time-weighted average fibre concentrations for years and fractions of years in the work area concerned. Cumulative exposures, expressed as fibre-yr/ml sampled air, were calculated as the sums of these work-area and time specific exposures. (The distributions of various dements in these exposures are included in Table 11J (26) Factory 8. Information was obtained on time worked during the 26 yr period at various factory locations involving exposure to asbestos at Factory B. Measurements of dust concentrations at some of these locations were also provided. However, there were many gaps in these records. A detailed study of the data showed that the material available might provide reasonably reliable estimates of cumulative dust exposures for only 55 (16%) of the 351 persons in the Factory B study group. The analysis of radiological results from Factory B therefore relates only to time periods during which persons were exposed, rather than to estimates of cumulative dust exposures. RADIOLOGICAL RESULTS Parenchymal abnormalities (27) Table 4 shows the distributions of film classifications to pneumoconiosis categories, by factory, reader, type of opacity and whether the films concerned were the earlier or later of the pairs examined. Similar distributions are shown for the 160 nonex posed controls. The mean interval between the 295 serial pairs of radiographs from Factory A was 16.9 yr (SD 5.1 >r). The mean interval between 351 serial pairs from Factory B was 10.8 yr (SD 7.1 yr). (28) A systematic difference between readers is evident m their interpretations of the distinction between small rounded and small irregular .opacities. :,leaders*, assessments of radiological abnormality in terms of `combined profusion^ Of^smail' 0uS353 t 1Q HS C d M M im t ON Assrsios 4. OimmilTlONS OF FII.M OLASSFirATION^. Factory A Factory B 0/ 0/- and as*d Category 0/D 0/1 1/0 I/I + N m 0/1 I/O 1/1 + ft Jmali opacities (Earlier films) Rounded Irregular Combined (Later films! Rounded Irregular Combined Reader 1 2 3 1 2 3 1 2 3 1 2 3 1 2 3 1 2 3 284 4 3 2 287 6 0 0 294 0 0 0 292 1 0 0 286 6 1 0 283 4 7 0 283 5 3 2 280 12 1 0 283 4 7 0 231 37 II 12 279 9 4 2 212 0 0 1 281 1 1 7 250 26 9 9 231 21 14 23 224 38 n 18 241 28 13 12 230 21 14 24 293 329 15 4 2 293 348 3 0 0 294 351 0 0 0 293 347 0 1 2 293 338 ! 1 2 0 294 325 12 10 4 293 326 15 5 4 2*1? 335 14 2 0 294 325 12 10 4 291 322 15 7 5 294 339 9 3 0 283 336 5 2 2 290 345 1 0 1 294 325 IS 6 2 289 296 26 18 91 291 321 15 7 6 294 318 22 7 4 289 287 31 20 13 350 351 351 350 351 351 350 351 351 349 351 345 347 351 351 349 351 351 S = number of films not judged `unreadable' and for which data sheets were completed according to protocol. Controls (A and B) 0/and 0/0 0/1 1/0 1/1+ M 155 3 2 0 160 S58 1 0 1 160 159 1 0 0 160 157 2 1 0 160 154 3 3 0 160 153 6 2 l 160 152 5 3 0 160 152 4 3 1 160 150 7 2 1 160 I it *?S S n O Heaith experience in two U K. asbestos factories--Appendix 3 Eorlier lilms 10 * -O o SC. f sr a%iug K Foctory A Factory B Qjl Later films Factory A Factory B Controls 1^ 23 i2 1 J (23 Reader Fig 1: Combined opacities- percentages of films classified as higher than category 0/0. 35 opacities are less variable, as is illustrated in Fig. I. The only conspicuous deviation from the general pattern there is the relatively frequent assessment of abnormality by Reader 3 among the later films from Factory B. (29) Table 5 compares readers' classifications in terms of & coefficient of consistency. This is a simple measure of the degree to which pairs of readers agree in their classifications of individual films (as distinct from an overall comparison of the proportions they judged to be other than category 0/- or 0/0). The index ranges from high consistency (97%) for earlier films with relatively little abnormality, down to 72% for later films from Factory A where the occurrence of radiological abnormalities was Table 5. Consistency |%) between pairs of readers in their classifications Of individual films Opacities I and 2 leaders I and 3 2 and 3 Factors A Pacton B Earlier Films Laier Films Earlier Films Later Films Controls Rounded irregular Combined Rounded irregular Combined Rounded Irregular Combined Rounded Irregular Combined Rounded irregular Combined 94 92 94 96 92 94 92 89 90 79 78 94 15 79 74 73 72 73 93 91 97 95 89 88 89 87 17 92 90 94 93 13 13 8? 79 SO % 94 % 94 90 88 91 IS 88 The figures shown are the numbers of concordant classifications on the 12-point scale, by two readers, expressed as a percentage of all validly recorded classifications by both the readers. M most frequent. The generally lower consistency for profusion ofcombined opacities a reflection of the higher frequency with which these signs were recorded- by Reader 1 (30) Table 6 records the numbers of men showing changes in profusion of mall opacities in the intervals between films, by factory, reade* and type of opacity. (Recall that individual films from a pair were not presented to readers at the same time, but were mixed with all other films and were arranged in random order.) (31) The difference between readers (Paragraph 28) in the wayjlbey classified the type of small opacities seen (round or irregular) affects the frequency with which changes are possible. Again, results with respect to combined opacities are less variable for Factory A, but there remains a substantial difference between Readers I and 3 in their recordings of positive changes at Factory B. (32) The columns headed `net change' in Table 6 do not reflect the amount of change recorded by a reader on the radiological scale. However, the n~t number of men found w ith positive radiological changes provides a simple index for comparing readers and factories. Note that the difference between Readers 1 and 3 in their assessments of combined opacity profusion in Factory B is reflected by a nearly six-fold difference in this index. Pleural abnormalities (33) On average, 4.4% of the films were noted as showing obliteration of the costrophrenic angle; 2.1% showed pleural thickening; and 0.4% were classified as showing pleural calcification In each case, rather more abnormalities were seen on films from Factory A as compared with Factory B, but there were bigger differences between readers than there were between factories, and there was no important difference between results from Factory B and the control films. These results are su mmarized in Table 7. One reader (3) noted pleural plaques on three radiographs from Factory A. Technical quality of radiographs (34) Readers were asked to record whether the technical quality of each film seen was acceptable. There were large differences between readers in these judgements. Reader I faulted 25% of the radiographs that be classified; Reader 2 faulted 12% and Reader 2 53 %. All three readers were less satisfied with films from Factory A than from Factory B; the average proportions faulted were 34 and 26%. respectively. Two of the independent film-readers (1 and 3) believed that on the basis of their familiarity with industrial chest radiography they were able to distinguish between films from Factories A and B. Reader 2 noticed differences in radiographic technique, but he was not aware that they were associated with one or the other factory. (35) Table 8 indicates how this factor might have affected readers'judgements of whether there had been a change in j. ofusion of small opacities in the intervals separating films in a pair. Where both films were judged as acceptable, the net proportion with at least one (positive) step of change (combined small opacities I was 17% for Factory A and 5.5% for Factory B This result (for a sub-set of'good' quality radiographs) is similar to that reported above for all the films (Table 6) It confirms thn the difference between the factories, as judged by readers' assessments of film quality, is not the sole reason for the apparently more frequent radiological changes among men from Factory A. 0uS^56 Health experience in two U K asbestos factories-Appendix 3 Taslf 6 Radiological changfs nvm IQ-26 yr intirvai.s Small opacities Reader N Factory A Number of lilm-pairs* showing radiological change! + ve -- ve lt ff) Net change (%) 100ta-bVN N Factory B Number of film-pairs9 showing radiological change! + ve - ve fa! lb) Net change (%) t00(a-byN Rounded Irregular Combined 1 2m 2 293 3 282 i 288 d1 292 3 288 1 289 2 297 3 288 St 14 1 9 44 56 64 SO 57 4 18.7 348 26 6 2.7 351 12 0 0.4 345 9 1 2.8 346 2 S 13 4 351 24 3 18.4 351 50 3 21.1 348 27 7 14.5 351 31 3 18.8 351 58 17 2.6 2 28 0 2.6 1 9.3 10 40 19 8.8 20 2.0 12 54 17 11.7 N * number oC filsn-pairs whose classifications were recorded validly by the reader concerned * Note that any two films from a pair were classified independently by any one reader. Radiological change' defined as change of one or more sub-categories on the ILO scale, ignoring changes between categories 0/- and 0/0. O C3 CD CO CJt <E fajpf.; "m Taw* 1. Wuwm &mmmut6t\. Factory A Factory!' Control ABJb No. of films: m 702 160 1452 - x %x % x% x% Costophrenic angle obliteration Pleura! thickening Pleural calcification Reader 1 41 2 22 3 31 Average 1 20 2I 3 29 Average 1 2 3 Average 2 0 7 6.9 3.7 5.3 S3 3.4 0.2 4,9 2.8 03 0 13 0.5 35 5.0 17 2.4 28 40 3.8 IS 2.! 00 14 2.0 1.4 2 03 00 5 0.7 03 9 .16 15 S.9 3 -1.9 41 29 6 -1.8 65 4,5 3.8 44 5 3.1 40 2.8 00 1 01 6 3.8 49 3,4 23 2.1 00 4 03 00 00 0 0 12 0.8 0 04 x number of films where abnormalities were recorded. The percentages tabulated are 100*. (number of films classified). Table 8. Radiological changes (combined small opacities) between hlm-faws in *elation to READERS" ASSESSMENTS Of TECHNICAL QUALITY OF FILMS IN A PAW 1st film. 2nd film: Acceptable Acceptable N x+ X- Film quality Acceptable Faulted Faulted Acceptable N x + x- N x + X- Faulted Faulted N X+ x-- Factory 4 Reader 1 14) 24 3 37 5 0 2 221 46 0 40 M 0 3 55 4 0 56 6 t Average over all readers (%) 17.7 0.7 16.5 0.8 74 9 22 6 11 13 0 2 2 16.8 2.4 40 12 51 106 34 31.1 4 1 0 33 Factory B 1 231 22 5 2 269 19 13 3 95 15 5 Average over all readers {%) 9.4 3 9 47 43 48 S4 23 50 8.7 5.1 57 3 29 5 128 26 2 3 9 15.9 6.5 16 I 5I 80 12 1 0 3 13.9 4.0 A? * number of film-pairs. x+ =number with positive radiological change, (one or more sub-category). x - - number with negative radiological change (regression, one or more sub-categorv i (36) Nevertheless, it is clear from Table 8 that the higher proportion of film-pairs in Factory A where both were faulted (19% on average, compared with 10% in pairs from Factory B) was associated with more frequent judgements of positive radiological change. The fortuitous lack of bias in the overall results recorded in Table 6 is due to the relatively few changes seen on film-pairs from Factory B where the earlier film was judged acceptable and the later film was faulted. 0GS358 Health experience in two U.K asbestos factories--Appendix 3 *59 Tabi e 9. Film quality and pleural abnormalfties PkuraJ abnormality Cosiophrtntc angle obliteration Pleural thickening Pleura] calcification Film quality Factory AB No. % No. % Control No. % All films No. % Acceptable Less than acceptable Acceptable Less than acceptable Acceptable Less than acceptable 65 5.7 6i 3.9 16 4.1 142 4.6 29 4.7 19 3.4 30 2.6 19 1.2 2 2.2 9 2.3 SO 4.0 58 1.9 20 3.3 5 0.4 4 0.7 to 1.8 2 0.1 5 0.9 2 2.2 00 00 32 2.5 7 0.2 9 07 T he numbers tabulated are the total number ofclassifications with the pleural abnormality indicated. 'Hie percentages are- (number of classifications with pleural abnormality) i00 *............ -----*--"-- 1 ........ ............. (number of classifications in film quality category) {37> Table 9 demonstrates that variations in film quality assessments did not affect the pattern of pleural abnormality assessments described in Table 7. Small opacities and smoking habits (38) Factory A. Table 10 shows that ail readers detected small opacities more frequently among smokers (and ex-smokers) than among non-smokers. Berry et at. {1979) have reported a similar finding from related data. The magnitude of the effect in terms of combined small opacity profusion is similar for the three readers, averaging nearly twice as many (combined) small opacity classifications among men who had smoked or who were still smokers at time of X-ray as compared with non-smokers. Table 10. Factory A; percentages Of latex films classified as category 0, 1 OR HIGHER, IN RELATION TO SMOKING HABITS AT TIME OF LATEX FILM Reader Percentage of films with opacity profusion greater than category 0/0 Small N rounded Irregular Combined I NS 63 16 79 94 S 185 70 162 20.5 Ex-S 46 196 19.6 2 NS 64 156 0 15.6 S 183 23 1 44 26 4 Ex-S 45 178 2.2 200 3. NS 61 0 11.1 1 i.l S 179 06 216 23.2 Ex-S 43 0 212 22.2 NS. non smoker: S. smoker; Ex-S. cx-tmoker: N. number of men (whose films were classified) in smoking category. 0uS359 ^:*r. > v ,, '`' '- ' v,, ; i' *,V`1^v: .'.'^.`^'`vp,, ' " - Fi ,, . - V* f . *. , , ' *' ,*-. *, . .-.-+ -+<f * r- r* ,; * T? -%T.. .- ^t*-t* "* . smokers' mdio^iph*. This, indicatesihat the rdioloiicIt iMps sTi from Factory AfFig. tjare not wholly attrifeutiSle ibsnioEfiff.Ait.thfet dassificitiomoflaterMmsfrom Factory B, asjudged by fteatHersl andl.showrfonly a marginally Higher proportion with combined smaH opacities than was fecordfcdfSr the control films. Note, however, that Reader 3 classified 18% of these films from Factory B into category 0/1 or higher, as compared with 6% of the control films. Radiological changes and dust exposure (40) Factory A. Table 11 refers to men from Factory A whose film-pairs showed evidence of increasing profusion of combined small opacities over the 10-26 yr intervals considered. The numbers concerned are expressed as percentages of men in sub-groups defined according to convenient but arbitrary ranges of four measures of dust exposure. The first of these measures, ,, is the cumulative exposure from start of work in asbestos areas up to the time of the earlier film. The second,' E* is the exposure during the interval between films. These quantities were estimated by direct proportion, using the detailed records of exposure up to the point nearest to the time when the films were made. The third measure, is the cumulative exposure up to the Table II. Positive radiological changes in Factory A, in relation to four MEASURES OF DUST EXPOSURE Ranges of dust exposure (fibre-yr/ml) 1 N% Reader 2 NX 3 N% <M 5-9 10-19 20 + 0-69 70-109 110-149 150-199 200-299 300 + 0-89 90-129 130-169 170-239 240-329 330+ 0-44 45-74 75-104 105-139 140 + H6 12.1 113 212 IIS 19.1 70 22.9 68 27.9 65 20.0 48 16.7 49 16.3 49 16.3 50 24.0 43 11.6 51 21.6 44 25.0 51 27.4 43 18.6 44 4.6 60 20.0 46 17.4 6T 22.2 28 32.1 44 11.4 58 172 44 25.0 63 28.6 28 25.0 44 11.4 58 20.7 44 18.2 63 19.0 28 419 50 8.0 50 20.0 49 163 54 11.1 53 113 52 11.5 52 19.2 50 24.0 so 20.0 50 24.0 49 36.7 51 25.5 49 184 29 3IO 50 20.0 29 20.7 49 16.3 29 41.4 48 83 48 18.8 47 17.0 67 9,0 66 12.1 65 13.8 56 28.6 53 17.0 S3 28.3 S3 32 1 54 20.4 53 24.5 60 25.0 61 21.3 61 26.2 The percentages shown refer to men for w hom positive changes in profusion of combined small opacities were recorded, N = number of film-pairs for which classifications were recorded by the reader concerned. The measures of exposure are: ,. cumulative exposure to lime of earlier film, E*. exposure in the interval between films. (. cumulative exposure to later film <,, + J. ,,. cumulative exposure up to a point approximate!) mid-wav m the interval beiween filmt, estimated as (,+ |h) Health experience in two U K. asbestos factories--Appendix 3 41 lime of the later X-ray. that is. the sum,+b. The final set of figures, d, is an attempt to approximate to the exposure up to the point when the observed change occurred. The estimate used for this purpose for each man was (,+ \Eb). (41) The low range of , confirms that the earlier radiographs obtained from Factory A did, in general, correspond approximately to the start of exposure to asbestos dust, and Table 11 shows no association between these early exposures and subsequent radiological changes. The mean exposure in the interval between films (b) was 163 fibre-yr/mi (SD 103 fibre-yr/ml). but, again, there is no obvious pattern of association between this measure of exposure and the grouped radiological results in Table 11. However, there is a positive correlation between percentages showing at least the earliest evidence of parenchymal changes and cumulative exposure up to the later film (.). A very similar pattern is evident in relation to d and, again, results from Readers 1 and 3 show a clearer correlation than those from Reader 2. These data are illustrated in Figs. 2(a) and (b). Readers 2 and 3 both recorded lower percentages of men with combined small opacities in the second exposure group than in the first. This apparent 'reduction* in response in the exposure group adjacent to the lowest may be attributable in part to removal from workplaces with relatively high dust concentra tions of men who showed early signs of disease after very low cumulative exposures (see 0-44 4J-M TJ-04 K-l 140 Oust pnDuir* ronqt, frttra-yr/ml Fit, 2. Percentages of men from Factory A showing positive changes in profusion of cc.nbined small opacities over 10-26 yr intervals, in relation to two estimates of dust exposure: (a) , r cumulative exposure to later ftlm.lb) * cumulative exposure up to a point approximately mid-way in the interval between films. (Data from Table II) Reader 1, 2*. 3A 41 Paragraph 9% Sinuhi! selection effect* may have distorted the rest'ftlationthiptef exposure and response at higher- levels of exposure. - (42) Factory B. information on time worked in jobs involving exposure to asbestos it Factory B was complete for 187 (98%) of those who had definitely worked in occupations with potential exposure to dust prior to 1951, and for 128 (96%) of those with no such prior exposure. Table 12 shows each reader's assessment of changes in profusion of combined small opacities for these two sub-groups in-Tdation to three categories of time worked in asbestos jobs after 1951 and up to 31 December 1976. The last column of this Table shows the amount of radiological change for each sub-group as the algebraic sum ofthe number ofsteps (positive and negativejofi the 12?point scale of radiological abnormality per 100 men in the sub-group concerned. These results arc summarized graphically in Fig. 3. Both Readers! and 3 recorded more.radiological change between films in a pair among persons with longer periods of exposure to asbestos while at the factory; the trend is clearest in the sub-groupof persons who had worked with dust or fumes before 1951. Table 12. Factory B; sms of change os the radiological scale (combined small opacity 100profusion) over 10-26 yr intervals per film-pairs classified in relation to time workh> with asbestos Exposure to dust or fumes before 1951 Exposure to asbestos after 1951 Reader Steps of change (combined small Net change/100 opacities) film-pair classified N +ve 100(<i.fcyN Some None <5 yr 5-10 yr SrlOyr < 5 yr 5-10 yr Ss 10 yr 1 76 4 2 76 10 3 76 s 1 49 7 I 3 3 0 2 49 i 10 3 48 li 1 C2 22 2 62 11 3 &: 43 7 5 2 7 1 r0 0 0 2 10 1 0 3 10 0 0 1 20 3 0 2 20 1 0 3 20 4 0 1 98 9 0 2 97 8 9 3 98 27 4 39 92 6.6 14.3 -4.2 6.2 27.4 14.5 58.1 0 10.0 0 15.0 5.0 20.0 92 -1.0 23.5 number of film-pairs classified validly. CORRELATION BETWEEN LUNG FUNCTION AND DUST EXPOSURE AT FACTORY A (43) At least one set of lung function measurements was available from 239 men, and at least t wo for 184 men out of the total of 295 men in the Factory A group. The correlation between the latest measurement recorded and estimates ofcumulative dust Health experience in two UK. asbestos factories--Appendix 3 so r- Reoder 5 43- <5 5-0 <5 5-0 <3 2-0 Durot.on of exposure to osbestos, yr Ftr; 3. Steps of change on the radiological scale (combined small opacities) over 10-26 yr intervals per 100 film-pairs classified from Factory B. tn relation to time worked with asbestos at Factory B. (a) Some prior exposure to dust or fumes, (b) No prior exposure, (c) Results of (a) and (b) combined. (Data from Table 12.) exposure up to the time of the test were examined. A linear multiple regression model was used to take account of age, height, weight and smoking habits at that time * The measures of lung function considered were FEVt, FVC, Tlco and the ratio FEVJFVC. (44) Results are summarized in Table 13. This shows that more than half of the total variability in the data remained unexplained by the variables included in the model. (45) The bigger teductions in total variability were for the FEVX and FVC (44 and 38%. respectively). These were the two response variables where the estimates of dust exposure made contributions approaching statistical sigmiicance at the 5% level (P * 0.06). Neither the Tlco nor the FEVJFVC ratio was correlated with the measure of dust exposure used. ADVERSE EFFECTS' Preliminary remarks (46) The Committee was advised that, solely for the purpose of this study, the earliest sign that the lungs of a worker were adversely affected `whether through The exposures were estimates by direct proportion, using data relevant to points nearest to the time when the lung function measurements were made. Smoking habits were represented in the regression models by dummy variables corresponding to men who smoked cigarettes only, other smokers, ex-smokers, and non-smokers. 44. B3HS Committee <rv Amqtm Table 13. Factory A; summary of results from multtflruoression analyses of the lailst long FUNCTION MEASUREMENTS AVAILABLE FOR 229 MEN < FEl\ FIC Tlco FE \\!FVC Mean 2,85 (1) 3.94 (1| 262 (m1 mm'1 mmHg'5 J 0 72 Crude correlation with dust exposure (r) . -0.271 -0.241 -0085 -0.182 Multiple regression coefficient for exposure ft.)* Standardized regression coefficient- 10 . . Percentage of total . variance accounted for -0.075 -0.090 0133 -0005 -1.88 " -1.93 0.35 -0.82 44 38 26 22 The regression coefficient with dust exposure is expressed as the change in Jung function per 100 fibre yr ml cumulative exposure. Data for explanatory variables were incomplete for 10 of the 239 men with at least one measurement of lung function exposure to asbestos dust or otherwise' would be the first appearance of one or more of eight conditions (see Appendix 1). The phrase `whether through exposure tc. asbestos dust or otherwise' reflects the difficulty in making an aetiological judgement based oniy on clinical examination of an individual. Application of these medical guidelines to an epidemiological study of the results presents a number of problems. (47) The first difficulty resides in the use of the phrase `whether through exposure to asbestos dust or otherwise" in the context of a study directed primarily at determining what level of exposure to asbestos dust is associated with the occurrence of the earliest sign of an adverse medical effect. The formulation implies that the occurrence of at least one of the nominated signs is to be regarded as a necessary but not as a sufficient condition for asserting that exposure to asbestos is responsible. Any attempt to estimate probabilities of the occurrence of these adverse effects as a function of exposure must therefore be qualified with the caveat that their occurrence may, in fact, be unrelated to asbestos exposure. (48.1 Secondly, with the exception of the radiological classifications, none of the medical data available were obtained under the kind of controlled, standardized conditions normally required in epidemiology. The lung function measurements were made, and the records of chest sounds were noied, in a clinical context. Different medical staff conducted these examinations over the years, using various conventions. No ^ata are available to estimate the variability associated with the application of the lung function tests. (49) Thirdly, determination of what constitutes `pleural shadowing" or `par enchymal changes' requires definition in terms of a standard radiological classification system and bearing in mind the variability between physicians making the classifications. (50) Fourthly, a decision on whether a particular value of lung function is `more than 20 per cent below the predicted value' is not as clear-cut in epidemiology as it might be in a clinical setting Whether or not such a discrepancy from the result predicted is statistically significant depends not only on the variability associated with the prediction but also on the variability of the data under examination. Moreover. 0u53 Health experience in two U K. asbestos factories---Appendix 3 45- choice of a suitable prediction may not be simple, because of ethnic, demographic, social-class factors affecting lung function. (51) Notwithstanding these and other difficulties, an attempt was made to apply the medical advice of the Sub-committee in an analysis of the available data. The statistical methods used are described below. Statistical methods (52) Seven criteria for determining the occurrence of an `Adverse Effect' so an individual were defined. For brevity, they will be identified by the letters A-G and will be referred to collectively as Adverse Effects (with capital letters and no qualifying quotation marks). (53) The Adverse Effects considered are listed in Table 14. The first two of these conditions (A and B) are interpretations of the medical recommendations concerning radiological abnormalities in terms of the film classifications described above. Table 14 List of Adverse Effects studied Notation Adverse Effect A At least two readers agreed that there were two or more steps ofchange on the profusion scale for combined small opacities over the interval between films B At least two readers agreed that a pleural abnormality was present on the later but not on the earlier film of a pair (where `pleural abnormality means at least one of pic. *! thickening, pleural calcification, or costophremc angle obliteration) C Unusual raie of change in FEV. 1 D Unusual rate of change in FVC V E Unusual rate of change in F/co j ,, ,, , , ,, 'Unusual defined in terms of distr.bution of residuals, see text, paras 54-58 F Any one measurement of FEVX FVC<010 C Chest sounds whicn did not dear on coughing or on any subsequent examinations Parenchymal changes were accepted as having occurred if at least two readers" independent assessments ofserial radiographs from a person showed two or more steps of change on the 12-point profusion scale for small combined opacities, irrespective of which lung zone was involved. Pleural shadowing was judged as being present if at least two readers agreed that a pleural abnormality was present on the later but not on the earlier films. (54) The letters C, D and E refer to changes in lung function. Thus, the procedures described below to determine the presence or absence of any of these Adverse Effects could be applied only to th -e persons for whom at least two serial measurements of lung function had been recorded. For each such individual, a lxast Squares estimate was made of the rate of change in the lung function measurement of interest, with a simplifying assumption that lung function falls linearly with age. The individually estimated rates of change in lung fur were then treated as the response variables in analyses which sought to relate the rate of change concerned to: (a) the initial value of lung function observed; (b) age at the time of the initial examination; (c) height as measured at the initial examination; (u) body weight as measured at the initial examination; (e) smoking habits as recorded at the initial examination. 46 fOHS CuMMtTTK ON AUKXTtK (55) A multiple linear regression mode! was used in which cigarette smokers, exsmokers, other smokers (pipe, cigar or mixed), and non-smokers were differentiated by dummy variables. The predicted value of the rate of change in Sung function for an individual (estimated from the fitted equation) was then subtracted from the rate of change as estimated from the measurements on the individual. The distributions of these differences (`residuals*), considered separately for Factories A .and B, were then used to define C. D and E arbitrarily as any value of a residual in the lower 20-percentiic of the distribution, assuming that the residuals are distributed normally with zero mean, and variance as estimated from the regression analysis. (56) If the residuals are distributed exactly normally, then this definition ensures that about 20% of them would attract classification as indicating an Adverse Effect. On the other hand, deviations from normality in the observed distributions would result in more or fewer such classifications. Thus, C, D and E refer to relatively severe rates of reduction in lung function which are not explicable simply in terms ofthe initial level of the functional measure concerned, age, height, weight or smoking habits. (57) D and E are approximations to the recommendations that Vital Capacity or Gas Transfer Factor measurements which fall faster than predicted by 20% could be regarded as an adverse effect; but note that D, referring to Vital Capacity changes, was attributed irrespective of concomitant changes in Functional Residu?*! Capacity. `Predicted' has been interpreted here as a prediction based on the internal evidence from the data, rather than on predicted `Normal* values derived from other sources. In this way it was hoped to avoid some of the difficulties referred to in Paragraph 50. (58) The definition of C (rate of reduction in FEV%) was not based on any suggestion from the Sub-committee's medical advisers. It was included because of the relatively high correlation of FEVt with dust exposure which emerged from the crosssectiona! analyses summarized in Table 13. (59) The presence or absence of F was determined for all persons for whom FEV% and F VC were recorded at least once at the same time, strictly in accordance with the advice from the medical members of the Sub-committee (Appendix 1). If the ratio FEVt/FVC was less than 0.70 then this was classified as F. (60) For Factory A. attributions of G were made io conform as closely as possible to the recommendations from the medical members of the Sub-committee regarding the occurrence of chest sounds indicative of an Adverse Effect. All serial records of medical examinations from the same man were inspected. At least two notations, at different times, were required of the presence of either `crepitations' or `crackles' or Tales' which did not clear on coughing on cither occasion, and with no subsequent record of such sounds which did clear on coughing. Where the data (from Factory A) indicated the presence of one of these chest sounds and no entry was made in the record to indicate that it did clear on coughing, then it was assumed that the sound noted had not cleared on coughing. Dated entries recording a medical examination with no reference to chest sounds were treated as `no chest sounds' on that occasion. (61) The above definition of G was not applicable to the Factor) B data, because the record cards provided to the Sub-committee contained references to the presence or ah -'re of post-tussive chest sounds only on the occasion of the latest medical examinations (see Paragraph 23). The presence of these sounds m the Factory B group is therefore symbolized by G' rather than G. (62) Collectively then, the seven Adverse Effects defined represent criteria, based 366 Health expenence in two U.K. asbestos factories --Appendix 3 .-7 on the data, which reflect, approximately, six of the eight clinical signs mentioned by the medical members of the Sub-committee. No attempt was made to interpret the absolute levels of Vital Forced Capacity or Gas Transfer Factor as Adverse Effects because of the high level of residua! variability found in the Factory A data when these measures were regressed on cumulative dust exposure, age, height, weight and smoking habits (Table 13). It was hoped that considerate , of rates of change in lung function might show a dearer association with dust exposure. Implicit in this approach was the hope that, even if an ear!} exposure-related functional disturbance is not detectable in the raw data, the associated more rapid rate of decline in function with age might be a more sensitive signal of possible severe respiratory dysfunction at a later date (Fletcher et ah, 1976). In the event, however, graphical analyses of the residuals which were used to define Adverse Effects C, D and E did not show any trend suggesting that they were correlated with dust exposure. Occurrence of Adverse Effects (63) Factory A. Table 15 shows the distribution of Adverse Effects found in the Factory A data. Results from 163 men met one or more of the seven criteria. The most frequently occurring effect was F, that is, at least one measurement of the FEVJFVC less than 70%. This result was recorded for 111 of the 239 men for whom at least one set of lung measurements was available. For 52 of them it was accompanied by at least one of the other Adverse Effects, including 16 of 26 men who also had chest sounds as defined (G). The relatively high number of occurrences of Fis consistent with the mean level of the ratio shown in Table 13 (72%). (64) Factory B. Table 16 shows similar distributions of Adverse Effects from the Factory B data. Results from 154 men and from nine women met one or more of the seven criteria. The total number of occurrences was 257. As in Factory A, the most Table 15. Factory A; distributions (a) or Adverse Effects, and <b) or men to combinations of . Adverse Effects (a) Number of Adverse Effects (b) Numbers of men with combinations of Adverse Effects shown A 22 B 25 C 23 D 33 E 34 F III C 26 Total 274 A6 B1 C2 D6 E9 F 59 G5 Tout no. of men 95 AB 2 AF 3 AG II BD l BF 7 CD 4 CE 1 CF 2 DE 3 DF 3 EF 6 EG 1 FG 8 42 ABF ADF BDF BEF CDF CFG DEG EFG 1 J l 2 6 1 1 l 14 ABDG ABEG ACEF ACFG AEFG CDEF DEFG 1 1 1 1 2 2 1 9 BCDEP 1 ACDEFG 2 t2 No Adverse Effects were recorded for 132 men. m SO^JE Cewwitrm AttMQtictt Tasu 16. Factor*.; mmmjnom fa) orAnvw* Efracrt; an #)cr mams to cqmmkations e# , Aovbw Emcn (a) Number el Advene Ejects (b) Number* of persons with combinations of Adverse Effects shown A5 B 18 C 43 D 39 E 59 F 88 G' 5 Total 257 A3 B1 C 15 D4 E 28 F 49 G- 0 Tot*!. BO. Of persons 107 AF 1 EE S IF 4 CD 1 CE 2 DE 3 DF 3 EF 8 FG' 1 3! BCD 1 BDF 1 CDE 1 CDF 4 CEF 1 CEG' 1 DEF 4 EFG' 2 15 CDEF 6 CDFG' 1 - ABCDF 1 - BCDEF 2 73 No Adverse Effects were recorded for 188 people frequently noted single Effect was F; 88 of the 313 Factory B workers lor whom lung function data were available had at least one examination where the FEVJFVC ratio was less than 70%. Tnere were fewer radiological changes recorded for Factory B (Table 6) and consequently also a much smaller number with Effects A or B. Only five records of post-tussive chest sounds were recorded, all were in men, and all occurred in the presence of one or more of the other Adverse Effects. Among those individuals whose results attracted at least one designation as an Adverse Effect (163 in both Factory A and Factory B) the distributions of persons with only one. with two, and with three or more Effects were similar (58,26 and 16%, respectively at Factory A; 66, 19 and 15% at Factory B). Derivation of probabilities of the occurrence of Adverse Effects at Factory A (65) Some of the analyses considered in Paragraphs 40-45 indicated correlations between the medical findings and the measures of dust exposure used; but there remains a high level of unexplained variability in the data. This implies that estimates of exposure-specific probabilities of the occurrence of Adverse Effects will be imprecise. If the exposures associated with the occurrence of particular Adverse Effects are known then these occurrences can be arranged in order of increasing exposure. In principle, the `Life Table' method, common!) used in actuarial science, can then be used to estimate probabilities that no Adverse Effect occurs up to particular exposures. The complement of such a `survival probability' is an estimate of the parameter of interest: the probability that an Adverse Effect occurs at an exposure less than a given value. (66) Berry et al. (1979) used this idea in their study of earlier data from Factory A. These authors referred to the results from their calculations as `observed relationships ... obtained by life-table methods'. But it is important to note that application of the method involves use of the product law of probability to generate estimates of cumulative probabilities. The results should not be confused with observed prevalences of the condition associated with increasing ranges of dust exposure (Table 11 in the present case) Gu Health experience in two U.K. asbestos factones -Appendix 3 49 (67) Application of the method to the result* reported now presents difficulties, because, as noted by Berry et al, `an unbiased analysis can be made only by using the times at which men with positive signs first reached this stage' (emphasis added). It is not enough to know that the exposure accumulated at that time was less than a particular value. (68) For effects F and G (FEVJFVC ratio <0.7 and chest sounds), use of estimated exposures to time of examination will probably introduce a relatively small error, since both F and G are associated with clinical features which are likely to have been noted by the factory medical staff soon after they occurred. (69) Changes in lung function, over several years, present a more difficult problem. The convention adopted for the analyses described below was to assume arbitrarily that the physiological disturbance which determined an abnormally severe rate of change began at a point in time mid-way between the initial and final measurement of lung function used. Estimates of the corresponding exposures were then made by direct proportion. (70) A similar convention was applied to the Adverse Effects involving radiological changes (A and B). The corresponding exposures are the Et defined in Paragraph 40. it has to be recognized that the radiologically defined events, A or B, may reflect the results of biological processes which began soon after the initial X-rays were taken. Or it may be that the changes occurred only a short while before the final radiographic examination. Use of an exposure corresponding approximately to that likely to have been accumulated in the middle of the interval concerned ensures that the (unavoidable) errors in estimating the true exposures of interest may occur on either side of the unknown true values. [Cumulative exposures up to the final examination (e), on the other hand, would certainly be biased; the errors involved could then be in one direction only--that of overestimating the required exposures.] (71) Figure 4 shows 22 estimates of probabilities of the occurrence of A, in relation to exposures Et. Figure 4 should be regarded as a convenient graphical representation of the range and distribution of the corresponding dust exposures. It should not be interpreted as graphical evidence of a real association between the Adverse Effect and dust exposure, because the ircreasing pattern of the plotted points is a consequence of the Product Limit method which generates a cumulative distribution of probabilities with respect to the time-dependent exposure levels under consideration * This property of the method used for estimating the probabilities may be illustrated by an example: Figure 5 shows results from 22 calculations of the kind which were made to generate Fig. 4; but in this case the 22 individuals whose ordered exposures were used to make !he calculations were not selected on the basis of the radiological results: they were selected at random from the whole group of (286) men considered. (72) Figures 6-10 were calculated from the observed data. They show similar representations of estimated probabilities for other Adverse Effects and they indicate the ranges of exposure measures used in their derivation (73) Figure II summarizes the results in the form of a (cumulative) plot of estimated probabilities that at least one of the seven Adverse Effects may occur In This is not to ray that there is tm real association, but only that the association is not to be inferred simply from the presentation m Fig 4. In Tact, Fig. 2 suggests strongly that the probability of finding radiological signs of parenchymal changes does increase with increasing exposure. 0uSa69 SO '10MS0bwtm*s.A*aarm Cumutotive exposure, E#, fibre-yr/ml Fig. 5. Figs. 4 aad 5. Product-limit estimites of probabilities of the occurrence of Adverse EfTeci A in 22 men (Fig. 4). and of 22 simulated events in the same group of 286 men from Factory A (Fig. S). In both cases the cumulative probabilities, on a logistic scale, are plotted against exposures E,,, defined in Paragraph 40 of the text, on a log scale. The 22 men whose exposures are shown in Fig. S were selected at random from the 286 for whom the presence or absence of Adverse Effect A was assessed. Figure 5 illustrates that graphical representations of cumulative probabilities as in Figs. 4 and 6-11 are not to be interpreted as if they were scattergrams. those cases where more than one Effect was noted in the same man, the measure used to order the event in relation to increasing exposure was that corresponding to the earliest occurrence. Again, it is assumed for this purpose that the observed radiological changes occurred at points in time corresponding approximately to the cumulation ofexposure d. Figure 11 shows that five Adverse Effects occurred before exposures amounting to 25 fibre-yr/ml had been accumulated. Two of them, including the earliest, were unusually rapid rates of reduction in Tico (Effect E; set also Fig. 8). The other three refer to Effects F (FEVJFVC<0.7), at 7 fibre-yr/ml; G (post-tussive chest sounds), at 8 fibre-yr/mi, and C (unusually rapid rate of reduction in FEV,), at 24 fibre-yr/ml. 370 Health experience in two U.K. asbestos factories--Appendix 3 31 30 20 tc 5: Is SO 1 ioo 200^300 Cumulative exposure, , f&e-p/m Fig. 6, Effect B. so : o 5 zsT" so '"Too * wo'soo ' "eoo Cumulative exposure, E,, fibre - p/m Fig. 7. Effect D. eo 3C 20 C s 82 8 ( OS y. 02 * 50 20 K) 5 -1------- 1 -i-------n--I--1. 25 50 i&O 200 400 Cumuiotive exposure, E,, fibre-yr/mt Fig 8 Effect E / i__ i iiii tO 25 5 WO 200 00 Cumulative exposure, E., fibre-yr/mt Fig. 9. Effect F. . sc , 20 HD - 5 t ....-i, --___ i_____ ___ K3 25 50 <00 200 600 0351- JL\ v_t...--_i__ i i .1___ jii * 02 5 O 25 50 IOO 200 400 Oxnutotive exposure, g, , f*re - yr/mt Cumulative exposure, E... fibre-yr /mi Fit. 10 Effect G Fig. 11 Any Effect. Fi a 6 f I Product-limit estimates of probabilities of occurrence of Adverse Effects B. D. E. F, G. and (Fig 111 of any one of the six Adverse Effects (A - G) before accumulation of the exposures indicated. N.B. (1) T he Ad *erse Effects are defined in Table 14. (2) is defined in Paragraph 40 of the text. (3) , ts an estimate of the cumulative exposure up to the mtd-potnt of the intervals over which the rates of reduction in rung function were determined (4) , and t are estimates of cumulative exposures up to the points when the Effects F and G first occurred (3) Where more than one Adverse Effect occurred in the same man. the exposure {,,,> shown in Fig. i I corresponds to the occurrence of the earliest of these Effects. (6) The interpretation of graphs of this kind is discussed in the text (Paragraphs 47, M, 71 and 74k the Factory A data suggest that improved estimates of the corresponding probabilities might be obtained by fitting straight lines to the points shows. This would be equivalent to postulating a logistic model as appropriate. Berry et a!. (1979) and Peto (1978) discuss this and alternative mathematical formulations for data of the kind considered here. Tie graphs indicate that a logistic mode! would be plausible for cumulative exposures higher than about 100 fibre-yr/ml. But the scatter of points below about 100 fibre-yr/ml show deviations which are not consistent with a straight line on the logistic-log scale, ft would therefore be unwise to use such fitted lines to estimate probabilities corresponding to exposures less than 100 fibre-yr/ml. ADDITIONAL COMMENTS (75) Paragraphs 27-42 of this Appendix describe results from a radiological study arranged by the Committee in January 1978. From an epidemiological point of view, these data are the most reliable of all those considered because they were obtained under controlled conditions. The Committee's interim statement, dated 25 April 1978, incorporated a large part of the radiological results, but it was noted that more data were being collected and that the statistical analysis was incomplete. Attention was drawn particularly to the need to document details of persons who had not completed exposure periods amounting to 10 yr or more in the interval 1 January 1951 to 31 December 1976 and who had been excluded from the study on those grounds although they had worked with asbestos for the first time after January 1951. The additional work on this matter was pursued during 1978 and 1979. The results arc reported now in Paragraphs 5-15. (76) The appendix to the Committee's interim statement included also an analysis of material describing the occurrence of Adverse Effects in the Factory A group. Those data are not reproduced here. They were based on a review by Factory A medical staff of their medical records. That review identified individuals who were considered to show evidence of having experienced an Adverse Effect, using clinical judgement and taking into consideration the views of the medical members of the Committee. (77) The Committee resolved subsequently to study the individual lung function and clinical records from Factory A in relation to the corresponding exposure data. Results from this work are described in Paragraphs 43-45. There was no evidence that the Tlco measurements or the ratios FEV}/FVC were related to the estimates of exposure to asbestos. (78) Nevertheless, the Committee had decided that the available medical data from Factory A. and that from Factory B, should be used to try to determine the occurrence of Adverse Effects as defined in the recommendations from its medical members. Implementation of that decision presented technical and conceptual difficulties from a statistical point of view. These are discussed in Paragraphs 46-50. (79) The way that these difficulties were tackled is described in Paragraphs 52-62. The methods adopted were arbitrary to some extent, of necessity, and they are therefore open to challenge However, they represent an effort to translate the essence of the items incorporated in the recommendations from the medical members of the Committee into unambiguous decision rules that could be applied to the available data. The rules were applied and the results arc reported in Paragraphs 63-64 Health experience in two U K asbestos factories--Appendix 3 S3 (80) The Committee was anxious to compare the implications of these results with those published previously (BOHS, 1968; Berry et ai, 1979). With this in mind, the available data were subjected to an analysis similar to that adopted in earlier studies, despite reservations about the validity of such presentations (Paragraphs 67 and 74), the ambiguity of how to interpret the Adverse Effects identified (Paragraph 47), and the absence of evidence that the lung function changes considered or the FEVJFVC ratios were correlated with the available data on exposure to asbestos (Paragraphs 62 and 45). (81) The results from this work are also reported above (Paragraphs 65-74), but it is appropriate at this point to reiterate two major qualifications that are attached to these findings; (i) The Adverse Effects described do not constitute diagnoses of disease. They are statistical definitions of events that might be associated with exposure to asbestds or that may occur also in the absence of such exposure. (ii) On their own the graphical representations of derived cumulative probabilities of the occurrence of these Adverse Effects cannot be interpreted as demonstrating necessarily that these Effects are correlated with cumulative exposure to asbestos dust. SUMMARY AND CONCLUSIONS (82) Radiological, physiological and clinical data from two asbestos factories have been examined in an effort to establish what cumulative exposure to asbestos dust is associated with the first signs of adverse pulmonary effects. (83) Persons included in the study had all started work with asbestos after 1950 and had then been exposed to asbestos for at least 10 yr. (84) An effort was made to assess approximately the extent to which criteria for inclusion in the study may have influenced results. As far as Factory A is concerned, it appears unlikely that the criteria for admission excluded many who had suffered serious health effects arising from their exposures (Table i). Nevertheless, it is recognized that some of those who had worked for less than 10 yr with asbestos (and who therefore were not studied) may have shown early adverse respiratory signs. (85) The data from Factory B cannot be regarded as a represenative wimple of possible adverse effects from exposure to asbestos. This is because the medical-care policy at this factory was to remove persons from exposure to abeio> whenever citmca! examination indicated early signs oflung function abnormalities. Such pcions were not included in the study, regardless of their exposure times, and some of them may have developed the functional abnormalities as a result of their work with asbestos. (86) Three physicians made independent assessments of chest radiographs from 295 men who had worked at Factory A. Collectively, the results show an association between the occurrence of parenchymal changes during 10-26 yr intervals and estimates of cumulative exposures to asbestos dust up to approximate points tn time when the changes are likely to have occurred (Table 11 and Fig. 2). (87) it was not possible to estimate cumulative dust exposures for most persons in the Factory B study group, but there was some evidence that longer periods of exposure at Factory B were associated with higher chances of developing small opacities on chest radiographs (Table 12 and Fig. 1). 0uS3?3 $4 ftOHS OiMMflm (js Amwstus (88) Small opacities were detected more frequently among smokers and ex smokers from Factory A than among non-smokers (Table 10), but the parenchyma? changes observed in the Factory A group are not wholly attributable to smoking habits. (89) Overall, readers judged 5.3% of films from Factory A and 3.8% of those from Factory B as showing obliteration of the costophrenic angle. Neither* of these results differed significantly from observations of similar abnormalities in thft.160 radiographs of persons who had not been exposed occupationally to asbestos. Other pleura! abnormalities were recorded even less frequently and their prevalence among asbestosexposed persons was not distinguishable statistically from the assessment of control films (Table 7). (90) Standardized levels of FEVl and FVC among men who had accumulated relatively high exposures in Factory A were lower than results from men who had received low exposures (Table 13). The negative correlations with dust exposure were statistically significant at the 6% level. Gas Transfer Factor measurements also showed a negative correlation with dust, but the residual variability in the date was such that the apparent relationship could easily have arisen by chance (P>0.7). (91) The radiological, physiological and clinical data from Factory A were used to identify persons who exhibited one or more ofseven statistically defined events possibly indicative of an early adverse medical effect of exposure to asbestos {Table 14). Estimates were made also of the cumulative exposures to asbestos up to the approximate times when these features were likely to have occurred. Cumulative probabilities of the occurrence of the defined events before the passage of these limes were calculated and they are expressed graphically as a function of the corresponding estimated exposures {Figs. 4, and 6-11). (92) The results suggest that for cumulative exposures up to about 25 fibre-yr/ml. the probability that any one of the seven defined events occurs is less than 2%. For exposures less than 50t fibre-yr/ml the estimated probability is less than 7%; for exposures up to 100 fibre-yr/ml the (cumulative) probability increases to about 17-20% (Fig. 11). (93) The statistical definitions of the events concerned are based broadly on guidelines suggested by medical advisers regarding `the earliest index that the chest of an asbestos worker was adversely affected from whatever cause'; they do not constitute clinical diagnoses ofdisease. The exposures refer, in the main, to dust clouds in the work areas where men are employed (`static' sampling), rather than to dust in the immediate vicinity ofindividuals'breathing zones. They approximate to time-weighted concentra tions of fibres in sampled air determined by the membrane filter counting method used at Factory A since 1977. (94) Much of the materia! used for this study originates from medical and environmental records that were not collected for epidemiological purposes. Even effort has been made in the data processing and statistical analysis to avoid pitfalls that can arise in this situation. However, a not easily quantifiable, but nonetheless important, residual uncertainty about the reliability of results is unavoidable in these circumstances. The above summary of findings reflects this uncertainty. Arknn*lrilgcmrn!< -- 1 am extremely grateful to Mrs Lir Copland and MissGinnte Henriksen who organised the arrangements for the film-reading and who helped me with data processing and staiisucal work 0GS37I Health experience in two U.K. asbestos factories--Appendix 3 55 ` REFERENCES Bexiiy. G . Guson, 1 C, Holmes, S., Lewinson, H C. and Roach, S. A. (1979) Asbestosis: a study of dose-response relationships in an asbestos textile factory, Br J. tnd. Med. 36, 98-112. British Ot cupational Hygiene Society: Committee on Hygiene Standards (1968) Hygiene standards for chrvsotile asbestos dust. Ann. occup. Hyg. 11,47-69 Fletcher. C. Peto. R., Tinker, C. and Speizer, F. E. (1976) The Natural History of Chronic Bronchitis. Oxford University Press, Oxford. Peto, J (1978) The hygiene standard for chrvsotile asbestos Lancet 1,484-489. Peto. J. Doll, R . Howard, S. V., Kinlen, L. i. and Lewinson, H. C. (1977) A mortality study among workers in an English asbestos factory Br. J. ind. Med. 34, 169-173. 00S375 Ont.iito rm*n efan Dupre, Pn.D. mu*ionef raser Mustard, M.D. ert Uffen, Ph.D., P.Eng . F.R.SC ctor of Research aid Dewens, Ph.O. |i Coun**!; n t taskm, IL.B. cuiive Co-ordinator- 3i Kann, M,P>. Royal Commission on Matters of Health and Safety Arising from the Use of Asbestos in Ontario 180 Oundas Street Wes 22nd Floor Toronto. Ontario MSG 1Z8 416/96S-1885 Our File No: The Commission has printed two background papers: "A Survey of Asbestos Policies in Canada with Particular Emphasis on Ontario"; and "A Review of Four Major Reports on the Health Hazards of Asbestos," In addition, the Commission has published several studies, including: Study No. 1 COLLECTIVE BARGAINING AND ASBESTOS DANGERS AT THE WORKPLACE, By Morley Gunderson and Katherine Swinton (ISBN: 0-7743-6834-9). Study No. 2 WORKERS' COMPENSATION AND ASBESTOS IN ONTARIO, By Peter S. Earth (ISBN: 0-7743-7024-6). Study No, 3 POLICY OPTIONS IN THE REGULATION OF ASBESTOS-RELATED HEALTH HAZARDS, By Carolyn J. Tuohy and Michael J. Trebilcock (ISBN: 0-7743-7043-2). CLITICS OF RISK: THE IDENTIFICATION OF TOXIC AND OTHER HAZARDOUS SUBSTANCES IN CANADA, By G. Bruce Doem (ISBN: 0-7743-6960-4). Study No. S LIVING WITH CONTRADICTIONS: HEALTH AND SAFETY REGULATION AND IMPLEMENTATION IN ONTARIO, By G. Bruce Doem, Michael Prince, and Garth McNaughton Study No. 6 Studv No. 7 WORKER ATTITUDES ABOUT HEALTH AND SAFETY IN THREE ASBESTOS BRAKE MANUFACTURING PLANTS, By Sally Luce and Gene Swiaaer (ISBN: 0-7743-7057-2). TOE TECHNICAL FEASIBILITY AND COST OF CONTROLLING WORKPLACE EXPOSURL TO ASBESTOS FIBRES, By Gordon M. Bragg (ISBN: 0-7743-7311-3). Study No. 8 ASBESTOS IN BUILDINGS, By Donald !'inchin (ISBN: 0-7743-7323-7). Requests for further information on publications, or other enquiries regarding the Commission, should be addressed to: Ms. Linda Kahn, Executive Co-ordinator, Rqyal Commission on Asbestos. 180 Dundas Street West, 22nd floor, Toronto, Ontario MSG IZt (*T*elephone: 416/90S-138S). ^ ^ .a. Ji, A dH * Additional copies of studies may be purchased in person at the Ontario Government Bookstore, 880 Day Street, Toronto, Ontario (Telephone: 416/96S-2054); or by contacting the Publications Mail Order Service, 880 Bay Street, Sth floor, Toronto, Ontario M7A 1N8. (Telephone: 416/97S-601S). *-4 003376nf background papers are available through the Commission.