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FILE NAME Talc TALC DATE 1979 DOC TALC051 DOCUMENT DESCRIPTION Journal Article - Cosmetic Talc and Ovarian Cancer efective to to the the families families families at at of risk risk Hos- neurologist University , and the many clinicians the Welsh Once and from the Commuter to combat Huntington's Chorea acaressed to S. H. REFERENCES Hunungon's Chorea in South Wales QuartJ Med DA The social personal and economic burden furgon's Chorea in South wales wales Br Psychiairn press Controversy COSMETICTALCTALC AND OVARIANCANCER C. YOUNG Cancer Treatment National Institutes of Health Bethesda 20205 U.S.A. The causes of ovarian cancer are un- known Theincreased incidence in in- dustrialised countries suggests an environmental in- experimental Epidemiological and clinical dat stem to link asbestos and talc with ovarian cancer Direct passage of talc or contaminated talc the through female female reproductive tract to the ovarian mayplay an etiological role Further systematic evaluation of talc and asbestos as ovarian carcinogens is needed INTRODUCTION the OVARIAN cancerthe most commonly fatal gyn^cological malignancy hasbeen increasing in frequency over th past 40 years Unlike cervical and endometrial cancer for which epidemiological correlations have led to a better understanding of risk factors and patho- , little is known about the causes of ovarian A role for environmental factors in the origin of ovar- ian cancer has been inferred from its higher incidencein industrialised industrialised countries The products of industry upon which mostattention has been focused are asbestos and tals Whereas the carcinogenic properties of asbestos are undisputed undisputed there is still controversy over talc.2-4 Although conclusive data are lacking various lines of esidence make it difficult to absolve cosmetic talc as a possible carcinogen carcinogen or promoter of transformation malignant ORIGIN OF OVARIAN TUMOURS The ovarian tumours tumours metastasise epitheliumepithelium is derived from specialised peritoneal cavity Ovarian by local extension and uncom- through extension the bloodstream In this they are similar to tumours of the mesothelium of bote pleuraland peritoneal origin as well as animal tumour models of foreign tumorigenesis Often the histological distinction between between ovarian peritoneal mesothehomas and carcinomatosis epidemiological epidemiological is difficult Thus where drawn distinctions between these arbitrary because these tumours ins tumori ASBESTOS ANDTALC and The case against asbestos is persuasive Itppromiters omites bronchogenic lung carcinoma mesothelioma ed beenfound ovarian cancer has " inin increased incidence la women with with asbestosis Female asbestos workers sF the died by Newhouse had an unusually high number of peritoneal neoplasms Women exposed to asbestos lly indirectly as members of households of abertos employees have been found to have a fold incre risk of mesothelioma Direct intrapleural injection asbestosin rats produces a highfrequency ofmeso Pe- liomasStrong evidence ofalink with ovarian conve conve was found by Graham and Graham who injected rabbits mice hamsters guineapigs and Dutch with e- molite asbestos The mice and hamstersshowed w lesions presumably because ofa layer protective of toneum surrounding their ovaries whichis absent in guineapigs and rabbits Both guineapigs andrabbits te epithe veloped an atypical papillary pattern of ovarian lial hyperplasia hyperplasia which the authors suggested was simu simu simu women to early ovarian epithelial tumours in Furthe- more they observed birefringent bodies in sections of out of twelve ovarian tumours and none of mine mora controls These bodies were thought to be asbests provided although no rigorous proof was Although Although asbestos fibres can be demonstrated in lungslungs they ar difficult to identify in mesothelial tumours and their presence would not be mandatory to establish an assout ation psbes with asbestos Mineral tale is closely related toa and the two substances are often found together ay in mineral deposits The pulmonary lesions of talc miles miles and miners13 were virtually virtual y indistinguishable indistinguishablinedistinguishable indistinguishable from the peritoneal longer Pleural aand nd tumours were until three to four times the expectedfrequency exposure control measures were instituted in 1950 in the U.S.A. A follow study showed that these measures had returned risks to normal An Italian less deposit study of talc millersand miners working a less contaminated by asbestiforms showed no increase t lung or peritoneal tumours Thus epidemiological dam could be interpreted as showing that the risk of develop- ing cancer from an occupational talc exposure was to contaminating asbestos EPIDEMIOLOGICAL STUDIES The epidemiological assessment of the risk due to talc is hampered by several factors Firstly talc exposure is so widespread that control groups are difficult to Men tify Talc is used in dusting powders deodorants chik chik crayons textiles pills including two of the six comroon brands of contraceptive pills soap insulating paints asphalt filler paper and condoms extensively in tive diaphragms It is also used matermater tas Ler RE OO TEBE 0 oO here,foo THE LANCET AUGUST 14 1979 . cessing Secondly consumer consumer tale products marketed before 1973 were variably contaminated by asbestos Rohi et al studied twenty products haloff which tained detectable amounts of tremolite up to Sbres weight Two brands had detectable chrysotile chrysotile October 1975 the Cosmetic Toiletry and Fragrance Fragrance Association C.T.FA C.T.FA revised their guidelines for talc and recommended that no sample containing asbestos matous lesion Lichtman et al. found tale which been deposited there 36 years earlier They also obsered obsered tremendous variation in the response to talc of tat tissues and the same tissue in different species lesions developing central necrosis within five days the absence of a polymorphonuclear response Talvis a diffuse lung disease characterised by perime perime d'as fibrosis was an occupational pneumoconiosis unti no- detectable by ray diffraction and optical microscopy with dispersion staining should be sold Therefore data collected on populations exposed before 1976 may re- flect the hazard of contaminating asbestos rather than sure limits were enforced in the U.S.A. Tale bodies IT sections of diseased lung as with asbestos boss to asbestosis suggest that tale elicits a strong definive reaction in man Pulmonary intravascular granulomas talc Unfortunately adherence to the revised C.T.F.A. C.T.F.A. guidelines is voluntary and monitoring of samples is left to individual manufacturers so that even now commercial tulcs are not certain to be asbestos Finally the epidemiological assessment of risk of talc exposure is seriously affected by the long latency of presumed talcinduced disease A prospective study might take more than forty years Newhouse has reported no evidence of health hazard among the predominantly female employees in a British talc factory in a study which needs to be continued another ten years to be confident in the negative result Information from epidemiological studies of talc exposure thus far must be considered in- conclusive EXPERIMENTAL STUDIES caused by intravenous injection of containing formulations can lead to vascular thrombosis and osis with pulmonary hypertension Thus there is doubt that talc is not as inert in man as in some species which have been used to assert its benignancy benignancy The most provocative evidence of a specific ass CLATAN between talc and ovarian cancer was that reported by Henderson et al who found talc particles 0-1-2 in diameter deeply embedded in 75 10 of 13 of arian tumours studied as well as some cervical and doe trial tumours No asbestos fibres were identified cer tainties about applicability of the technique used time report have cast some doubt on the validity of the undings but several subsequent papers from the group27-31 lend weight to the original contentions Access of talc to the peritoneal cavity is most likel Animal studies on the effects of talc have been reviewed by Hildick Talc was not found to be mutagenic in vitro but neither is asbestos.18 vivo tests and several acute and chronic exposure models failed to show any carcinogenic potential over a wide dose range Though these studies were conducted with talcs ofundefined chemical and physical characteristics their uni- through the vagina Studies of the transport of particles in the human female reproductive tract have shown that motile inert carbon particles deposited v1 vagina can be recovered 30 to 35 min later in th . pian tubes TALC AND OVARIAN CANCER formly negative results provide the basis for Hildick- We suggest that cosmetic tale can be deposited u Smith's conclusion that concern . . . about the possible vagina through repeated application to the perineura health hazard from consumer exposure to cosmetic talc through use of a dusted diaphragm or condom Luc- is unwarranted Yet data on the cellular response to ing intercourse As it is carried through the f^mule talc are sparse Allison observed that like other agents of chronic inflammation including asbestos reproductive tract most particles are removed by defence mechanisms but an occasional particle can be ingested by macrophages with attendant release of lyso- deposited on the surface of the ovary Possibly sumu- somal hydrolases Lung fibroblasts take up talc particles lated by gonadotrophins and ovarian hormones the up to 10 um in diameter and these particles penetrate talc perhaps contaminated with asbestos alters the the cell membrane but not the nuclear membrane Chry- responsiveness of the ovarian epithelium which ulti- sy sotile asbestos fibres are handled in a similar way No mately proliferates autonomously gle studies of the effects of talc on cell metabolism have been This hypothesis seems to be consistent with the teh reported Intratracheal instillation of talc in Syrian known facts about ovarian cancer With talc exposure Laut golden hamsters has been shown not to induce respira- beginning in infancy hormonal stimulation with tory tumours though fibrosis was not uncommon Ben- menarche and assuming a 20-40 year latency period pyrene alone also failed to induce respiratory peak incidence of ovarian cancer might be expected in tumours However talc and pyrene together the 40-60 year age group This is in fact the observed induced tumours in 80 of hamsters treated Whereas group of peak incidence The hypothesis would prz- the bulk of evidence suggests that talc is not an indepen- dict the observed high incidence of bilaterality It would dent carcinogen it may act as a carcinogen or pro- moter None of the animal studies has clarified what talc does at the cellular level CLINICAL EVIDENCE also predict that anything interrupting the patency the female reproductive tract should protect against against ovarian cancer An epidemiological report from the Mayo Clinic shows that hysterectomy is associated with a lower risk of ovarian cancer Similarly patients Clinical data provide the bulk of evidence for a role for talc in human disease The development of fibrous adhesions from talc has been known since 1933 and for this reason tale has been used to obliterate pleural cavi- ties in diseases causing chronic effusions In a granulo- with a history of tubal disease e.g. scarring from pelvpielvcic inflammatory disease should have a lower incidence of ovarian cancer Although prediction has not oma directly assessed data sugsugggesteingsting a lower attack ta sexually active women may indirectly support THE LANCET AUGUST 15 1979 31 31 31 observed increased risk of ovarian primiparous and nulliparous women can uninterrupted cyclical hor- 23 23 Kuschner M. The J Burns Amberson lecture the causes lung cer wf Rev Respir Dis 1968 5x 573-97 24. Lichtman AL McDonald JR Dixon CI Mana FC Faiz granuloma bng Os Gynecol Gynecol Os 25 25 25 Hopkins GB Twlor 531-58 granulomatosis Am R 1970 101.19-3 101.19-3 26 Henderson WJ Juslin CAF Turnbull AC Griffiths K. Tale and - Kisl hee of the ovary and cervix J Obstet Gynecol Br Comm 1971 : 27 27 Henderson WJ The use of analytical electron microscopy in the stud Chies Chies eign and naturally occurring minerals in biolageal tissues Micr the removal of detectable asbestos from talc Enforcing first step to protecting consumers from potential Investigators Investigators should focus on detecting the talc most closely parallel those of women identify particles in ovarian specimens should be intensified The epidemiological study of Newhouse and her colleagues17 in Great Britain on the risks of systemic exposure in female talc workers should be repeated in another geographical location Further- of more a study on the risks local use of talc in the geni- tal region should be undertaken Finally clinicians should collect data on the use of cosmetic talc by their 3-131-3 Grths 28 Grths K Henderson WJ Chandler JA Josian CAF Ovaran some new analytical approaches Postgrad Meaf Meaf 1973 09-72 29. Henderson WJ , Chandler JA Blundell G Grifhths C Davies JD 7 2.1 oc tyet- analytical of electron cation electron microscopy to the study of diseased h yaa! tissue J Microsby 30 Henderson WJ Griffiths K. Identification of particles in ovarian tissu fa Brush MG Taylor RW eds Gynecological malignancy circu Wil iams Experimental studies Baltimore Wilkins 1975 225-4 31 Henderson WJ Hamiton TC Grifths K. transport ovarian tissue Lancet 1979 499 32 Egh GE Newton M. The transport of carbon particles in the human mal- Ster reproductive tract Fertil 1951 151-5 33 Anneges 7 Strom H Ducker DG Dockerty Dockerty MB cancer incidence and control study 34 Beral V Fraser P Chilvers C. Does pregnancy cancer Lancer1978 vr 1033-6 Round the World patients with ovarian cancer Data obtained from such an approach may justify the absolution of talc which has already been claimed But until such information is collected The Lancet's statement that it seems unlikely that future exposure to cosmetic talc of the specifications now agreed to by major manufacturers will present a health hazard must be taken on faith alone Requests for reprints should be addressed to R. C. Y. REFERENCES Dongman CH Enology of cancer of the human ovary a review J Nat Cancer Inst 1974 53 1603-13 Bjer HP Arlon R. c a possible occupational and environmental car- 3 Hck Ongen.J Occup Med 1973 15 92 7 SSmmiithth Gr The biology of tale Br J Indust Med 1976 33 2'7-29 1. 4 Anonymous Cosmetic tale powder Lancet 1977 1348-9 KG Johnson KH Buoen LC Foreign body tumorigenesis CRC Crit Toxicol 1976 353 94 4 J R. Mortality from lung cancer in asbestos workers Br Indust Med 81-6 Wagner JC Sieggs CA Marchand P. Diffuse pleural mesothelioma and asbestos exposure in North Western Cape Province Br J Indust Med 1906.17 260-71 S. Keal EE Asbestosis and abdominal neoplasms Lancet 1950 ti 1211 6 9 Newhouse ML Berry G Wagner JC Turok ME A study of the mortality Med of female asbestus workers Brindust Brindust Brindust 1972 29 134-41 10 Vianna NJ Polan AK occupational exposure to asbestos and malignant in mesothelioma females Lancet 1973: 1061-3 Mesotheliomas in rats following inoculation with Cancer Br Br Graham Graham R. Ovarian cancer and asbestos Entron Res 1967 1 Messite J Kooyman O Zaki MH Mortality among talc miners rillers in New York State Arch Environ Health 1967 14 663-7 Kl^,rtell M Messite J. Zaki MH Mortality experiences of talc workers a follow study Occup Med 1974 15 345-9 15 Rubio GF Stansett G Piolatto G Romaro CA. Mortality study of tale miners and milles J Occup Med 1975 18 186-93 in Rohl N Langer AM Selikorf IJ et al Consumer talcums and powders Funeral and chemical characterization J Toxicol Environ Health 1976 2 255-84 ML Miner BF Moore WKS Paper given at seminar on Biology in Health Products Cardiff May 1976 cited 5 BN unpublished observations 15 An An AC Paper given at seminar on Biology of Tale in Health Products Cardif May 1976 Schorlemmer HI Davies 1 Hylton W Gugig M Allison AC The selective 1 sosemal acid hydrolases from mouse peritoneal macrophages sumul of conic inflammation Br Pat,, hol 1977 58 315 26 WJ Blundell G Richards R et al Ingestion of talc particles by Res lung foroblasts Enero 1975 9 173 8 Stenback F. Rowland I. Role of tale and benzoja pyrene in respiratory tumor formation Stand Respir Dis 1978 59 130-40 From our Correspondents United States THE PUBLIC'S RIGHT TO KNOW If there is one thing that distinguishes the US from the U.K. it is the publicity that surrounds crimes and tause accused of committing them In Britain the discussione discussione discussione media of judice matters is sharply circumscribed ( 1s U.S. comment has been very free far too free some rea In a notorious or scandalous case there may be an argue mous publicity on every aspect including every detail ot toe accused before the case even comes to trial All th os defended by the media as part of the public's right to any embedded in that sacrosanct document the U.S. Constitutio But the Supreme Court has been busy in these last te weeks It decided in the Weber case that affirmative action wax inequality permitted in favour of minorities the victims of inequality the past even if other racial groups were thereby disadva taged The case differed from the Bakke case in that no specif involved The Court ordered extensive ingto ingto quota was whether the lud will enforce racial balance in schools though be available well spent another matter Finally the fury of the media and the libertarians the Court decided by a majority that a judge if both sides agreed could excinc the Press and other media from the courts in criminal and 02: cases The judgment came as so often happens from 4 tively trivial legal fracas in New York State But by implication it could have extensive repercussions Justice it is sand may certainly be done but it certainly will not be seen to b done under this dispensation and the public will not know Ve can expect considerable hubbub to develop over this decision The public right to know has been in the foreground ance the Watergate affair when the public were denied this right deliberate concealment It led to the Freedom of Information Information Law by which public access to all Government documents now permitted In theory this is admirable and scorta fingers are pointed at Britain where so much secrecy prev There are also some undesirable aspects which are now cor to the fore particularly those involving the F.B.I. and archives Every little crook and nanny as it were is searchin little nook and cranny of these archives of course the etvaexrpyayers expense for something or other Some are '* ki for the names of those who informed on them to the police or betrayed Party comrades others are looking for opportunities