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FILE NAME Talc TALC DATE 1979 DOC TALC141 DOCUMENT DESCRIPTION Medical Journal Article - Survey of the Term Effects of Talc and Kaolin Pleurodesis sis should psy should specimen d biopsy preliminary of pleural 106 of pleural icans Nig 1 Br J. Dis Chest 1979 73 285 A SURVEY OF THE TERM EFFECTS OF TALC AND KAOLIN PLEURODESIS RESEARCH COMMITTEE OF THE BRITISH THORACIC ASSOCIATION AND THE MEDICAL RESEARCH COUNCIL PNEUMOCONIOSIS UNIT Summary Of 210 patients who underwent pleurodesis with iodized talc or kaolin 14 to 40 years previously all but 11 were traced There was no increased incidence of lung cancer and no case of mesothelioma INTRODUCTION Exposure to high concentrations of talc dust in mining and processing in the USA has been shown to cause pulmonary fibrosis and a four increase in the incidence of malignant tumours of the lung and pleura Kleinfeld et al 1967 However this dust contained other silicates including tremolite and anthophyllite and the incidence of these malignant tumours fell and approached the expected mortality when dust levels were reduced Kleinfeld et al 1974 In a controlled study of Italian talc miners and millers exposed to a very pure type of talc Rubino et al 1976 were able to show a lower than expected incidence of lung cancer although the mortality rate amongst the miners exceeded the norm because of the high incidence of pneumoconiosis silicosis with or without tuberculosis In Great Britain Henderson et al 1971 described talc particles in association with carcinoma of the ovary and cervix confirmed later by analytical electron microscopy Henderson & Griffiths 1975 Jackson and Bennett 1973 reported a chest wall tumour of adenocarcinomatous type developing within three years of iodized talc pleurodesis for recurrent spontaneous pneumothorax but it is unlikely that the talc played any causative role in the development of this tumour Animal studies using inhalation and intrapleural injection of an Italian cosmetic talc have failed to demonstrate a carcinogenic effect Wagner et al 1977 Talc which is mainly a hydrated magnesium silicate is marketed in different grades the higher grade being used for cosmetic and pharmaceutical purposes and the others in industry Hildick 1976 Cosmetic talc consists of flake particles and is largely free of the long thin fibres of asbestos minerals such as tremolite actinolite and anthophyllite which are closely related to it in the natural state These contaminate some industrial talcs however and are possibly responsible for the fibrogenic and carcinogenic effects already referred to In Britain talc has been used by intrapleural poudrage since 1935 to induce pleurodesis usually for treatment of recurrent spontaneous pneumo- thorax A follow of such patients should reveal any possible carcinogenic effects of talc and a subcommittee was set up by the British Thoracic Association and Medical Research Council Pneumoconiosis Unit to organize a survey * Members of the subcommittee were A. G. Chappell chairman A. Johnson coordinator J. Charles J. C. Wagner R. M. E. Seal G. Berry and D. Nicholson 286 British Thoracic AssociationMRC Methods In order to obtain a large number of index cases 11 thoracic centres were approached but only three were able to participate Sully Brompton and Harefield Hospitals At each centre medical record indexes and surgical registers were reviewed and the notes scrutinized to identify patients who had received pleurodesis with talc or a like mineral such as kaolin china clay hydrated aluminium silicate before January 1961 so that a minimum observation period of 14 years was possible Tracing the patients proved a difficult and lengthy task Methods used included direct written approaches to patients and general practitioners family practitioner committees the Office of Population Censuses and Surveys OPCS and foreign embassies A large number of patients would have remained untraced without further assistance from two field workers with experience . of epidemiological studies who checked information for accuracy and made visits to discover the present state of index cases not traced by letter The results were assessed by comparing the number of observed deaths with the number expected by the subject method Case & Lea 1955 multiplying years of risk by death rates The death rates for England and Wales were taken from tables compiled for studies of this kind Institute of Cancer Research 1976 These tables give specific death rates with age in year groups and also calendar year in year groups up to 1966-70 The study extends beyond 1970 and the rates for 1966-70 were used for the later years Deaths from all causes and also from cancer of the lung and pleura have been considered Excess mortality has been tested by treating the observed number as a Poisson variable with expectation equal to the expected number RESULTS Two hundred and ten cases were collected from the three centres Table ) The Sully patients many of whom had chronic lung disease such as chronic bronchitis emphysema and pneumoconiosis received intrapleural kaolin as treatment for spontaneous pneumothorax between 1956 and 1960. All the Brompton and Harefield patients received intrapleural talc over half having been treated before 1945. In 22 Brompton and 70 Harefield patients iodized talc was used to produce pleurodesis in patients with bronchiectasis and other malignant disorders before lung resections man with a carcinoma i radiotherap significant + patients we Table II patients 36 three quinq the already for 21 of th Hospital Sully Brompton Harefield patients No. of malpeastients 63 50 43 24 104 54 210 128 Table I. Outcome of the study alive Contanadctewedllalive Untraced but believed alive 45 26 _ 81 2 152 2 Emigrated and untraced _ 3 . 6 9 Dead lung cancer in parentheses 18 14 1 15 2 47 3 One hundred and fifty patients have been contacted and are well whilst a further two are thought to be alive OPCS but have not been traced Table I Follow data are available on nine emigrants for periods ranging from 14 months to 24 years but attempts to locate them have failed There were 47 deaths including three from lung cancer Table II Two patients with lung cancer had a tumour on the side opposite to the pleurodesis with intervals of 18 months and 19 years between pleurodesis and death The third case was a year This study Later repor contaminan of carcinom only in rec ched but only centre medical entify patients clay hydrated f 14 years was ncluded direct tees the Office per of patients ith experience sits to discover 1 the number by death rates es of this kind ge in year > beyond 1970 so from cancer y treating the ber ) The Sully . emphysema us pneumoceived intra70 Harefield niectasis and Dead lung cancer in parentheses 18 14 1 15 2 47 3 1st a further ow data 4 years but atients with ervals of 18 year Talc and Kaolin Pleurodesis 287 Table II Observed and expected mortality Hospital Sex Sully Brompton Harefield Men Women Men Women Men Women All causes Obs 18 0 9 5 ' 11 4 Exp 9.1 0.8 3.4 4.0 7.1 4.6 Lung cancer Obs 0 0 1020 1020 1020 1020 Exp 0.84 0.03 0.36 0.06 0.72 0.13 Total 0.01 + 0.3 47 29 3 2.14 man with an oat cell carcinoma who died 32 years after pleurodesis The site of the carcinoma is not known and at autopsy no tumour was found but he had received radiotherapy Although lung cancer deaths were no greater than expected there was a significant excess of observed over expected mortality for all causes the two untraced patients were assumed to be alive for the purposes of this calculation Table III shows that although follow was longer than 15 years in the majority of patients 36 deaths occurred within 15 years of pleurodesis The observed deaths in these three quinquennia were significantly more than expected The probable explanation is the already high incidence of respiratory disease in these patients at the time of pleurodesis for 21 of the deaths were due to respiratory causes Table III Duration of follow after pleurodesis Duration of follow years 0-4 5-9 10-14 15-19 20-24 25-29 30-34 35-39 Deaths 16 9 11 6 2 0 2 1 Others 4 2 5+ 70 7 3 45 127 Total 47 163 * Emigrated Includes one emigrant DISCUSSION This study was devised in 1974 because of the suggestion that talc might be carcinogenic Later reports quoted in the introduction have not supported this view and asbestos contaminants were possibly responsible for the early reports of an increased incidence of carcinoma Strict standards for the manufacture of cosmetic talc have been adopted only in recent years Editorial 1977 We have been able to ascertain that talc B.P. 288 British Thoracic AssociatiMoRnC was used at Brompton and Harefield Hospitals even before 1945. Indian Finex has been used extensively for this preparation in the past and is unlikely to have contained any fibrous amphiboles but we have no idea of the composition of other B.P. talcs over the past 40 years Pooley 1978 It was decided to include patients treated with kaolin because of its chemical similarity to talc and its propensity for producing pulmonary fibrosis after prolonged and heavy exposure even though no carcinogenic effect has been ascribed to the mineral All the Sully patients received kaolin rather than talc for their pleurodesis but even if they are excluded from the analysis of lung cancer deaths Table II the ratio of the observed to expected incidence is still not significant P 0.14 Tracing of patients proved very difficult particularly those from Brompton and Harefield cases over half of whom were treated prior to 1945. No attempt was made to examine or ray the patients who were scattered throughout the country It was felt that this would prolong the study and prove unrewarding as very few asymptomatic cases of mesothelioma would have been expected for Elmes and Simpson 1976 in their study of 327 cases found a mean interval between onset of symptoms and arrival at hospital of only 3.4 months We have therefore found no increased incidence of lung cancer and no case of mesothelioma in the series of 210 patients 88 of whom have been followed for between 15 and 30 years and 75 for 30-40 years after pleurodesis ACKNOWLEDGEMENTS We are grateful to Miss C. Exall and Mrs B. Norman for their painstaking work in tracing many missing patients and Mrs B. Gamble and Mrs I. Speck for secretarial assistance REFERENCES CASE R. A. M. & LEA A. J. 1955 Mustard gas poisoning chronic bronchitis and lung cancer Br J. prev soc Med 9 62 EDITORIAL 1977 Cosmetic talc powder Lancet 1 1348 ELMES P. C. & SIMPSON M. J. C. 1976 The clinical aspects of mesothelioma Q. Jl Med 45 427 HENDERSON W. J. & GRIFFITHS K. 1975 Identifications of particles in ovarian tissue In Gynae- cological Malignancy Clinical and Experimental Studies ed M. G. Brush and R. W. Taylor pp 225-40 London Bailli^reTindall HENDERSON W. J. JOSLIN C. A. TURNBULL A. C. & GRIFFITHS K. J. 1971 Talc and carcinoma of the ovary and cervix J. obstet gynaec Br Commonw 78 266 HILDICK G. Y. 1976 The biology of talc Br J. indust Med 33 217 INSTITUTE OF CANCER RESEARCH 1976 Serial Mortality Neoplastic Diseases Vol 1. Deaths and Death Rates by Sex Age Site and Calendar Period London JACKSON J. W. & BENNETT M. H. 1973 Chest wall tumour following iodised talc pleurodesis Thorax 28 788 KLEINFELD M. MESSITE J. KOOYNAR & ZAKI M. H. 1967 Mortality among talc miners and millers in New York State Archs envir Hlth 14 663 KLEINFELD M. MESSITE J. & ZAKI M. H. 1974 Mortality experiences among talc workers a follow study J. occup Med 16 345 : POOLEY F. D. 1978 Personal communication RUBINO G. F. SCANSETTI G. PIOLATTO G. & ROMANO C. A. 1976 Mortality study of talc miners and millers J. occup Med 18 186 ; . WAGNER J. C. BERRY G. CoOKE T. J. HILL R. J. POOLEY F. D. & SKIDMORE J. W. 1977 Animal experiments with talc In Inhaled Particles IV ed W. H. Walton pp 647-54 Oxford and New York Pergamon Electron mic that the tum matory cells Fibroblasts relationship | Since the fi 1963 and : manifestation cally differer cell granulo paper the ca not followed A year solitary lesion free and 1 a sharply defir on the bronc | cytology reve | protein was 8 The patien | an shape was enca ! was no abnor necrotic areas | hospital in M radiograph