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FILE NAME: Talc (TALC) DATE: 1979 DOC#: TALC051 DOCUMENT DESCRIPTION: Journal Article - Cosmetic Talc and Ovarian Cancer . HK L-.''Lii, auolm IS. 1y~9 >P able. e*_oromi:uv ',,sUHa-ke, and ef-^ctivr:, as we!! as b.v' ' a-;,eptib!e anJ heirfui to the farrihes at risk of IK ` * v ,, v ' ;/ V .,,c- Dr Chj;.=N -.ms, cor.-'ukjne neurologist, l,V.iver?hy K u y i'c-. Mr< T u j 'ncj ' ofkf, anJ the many cl.-.idana in r r-cen . .`J .n :h:-i'`<or.s. '! -, t) H w ; -,J. C.OV.. \; .j- *.,;7cr:j w *rr.in;$ for?, the Vd.-h O.hce and thtf O -irM U ie u> combat H um m gwn\ Chorea f . . - -; n n r r i P . o >h o u le ire a c a r e a d to P. S. H . ?.r. Fi RHSCcS l S-> , J l'?., ..rs R. H,_ni;.-, i ,.on'5 Chorea >n South Wales. Q 'u rt J M sJ :~`'?-25 " . i . A- turner ?S. v.a<rr L)\ The social, persorui and economic burden . : r .L r a r j:o n `s C h o rea.? S n tth 'a lev B m J Ps\-ch:M'\n pris?}. Controversy COSM ETIC TALC AND OVARIAN CANCER D. L. I.os'oo R. C. Young Mzdio.ne Branch. Division of Cancer Treatment, National Canoe'' Institute, .\ r.tiu Institutes of IIealth, Betkesdat Mar-/und 20205, U .SA . S u m m a r y The cause- of ovarian cancer are un known. The increased incidence in in- dustnak-ed countries suggests an environmental in fluence. Epidemiological, experimental,, and clinical date >eem to link asbestos and talc with ovarian cancer. Direct passage of talc or asbestos-contaminated talc through the female reproductive tract to the ovarian surface may play an Etiological role. Further s)stcmatic evaluation of talc and asbestos as ovarian carcinogens is d. .:. " INTRODUCTION Ovarian cancer, the most commonly fatal gynscologicni malignancy, has been increasing in frequency over t h : pas: 40 years. L'n'ike cervical and endometrial cancer, for which epidemiological correlations have led to a better understanding of risk factors and patho genesis, hide is known about the causes of ovarian cancer.1 A role for environmental factors in the origin of ovar ian cancer has been inferred from its higher incidence in industrialised countries. The products of industry upon which most attention has been focused are asbestos and talc. Whereas the carcinogenic properties of asbestos are undisputed, there is still controversy over talc.2-4 Akhough conclusive data are lacking, various lines of e.iderce make it difficult to absolve cosmetic talc as a possible carcinogen, co-carcinogen, or promoter of malignant transformation. O R IG IN OF O'. A R IA S TU M OU RS The ovarian epithelium is derived from specialised me.othuhal cells in the peritoneal cavity. Ovarian n r: !.!.-- tend to grow bv local extension and uncomn ;r h , metastasise through the bloodstream. In this regard they are similar to tumours of the mesothelium oi hot.', pleural and peritoneal origin as well as animal ra n e e - models of foreign-body tumorigenesis.5 Often the hi-roiogical distinction between ovarian tumi.,.;:. pemoue-.i! niewitheliomas, and carcinomatosis peri: a e: is diriicidt. Thus, where epidemiological studies !'a, drawn distinctions between these entities they :n.\, re arbitrary because these tumours may have similar orig ins. A SB E ST O S AND l.-'.I.C The case against asbestos is persuasive. It pionw.es bronchogenic lung carcinoma'' and mesothelioma,' nd ovarian cancer lias been found in increased incidence in women with asbestosisd Female asbestos workers died by New-house0 had an unusually high number of peritoneal neoplasms. Women exposed to asbestos uy indirectly as members of households of ,..-bc-''o.employees have been found to have a ten-fold mere.. ,o-_ risk of mesothelioma.10 Direct intrapleural injection of asbestos in rats produces a high frequency of rr.esc U'eliomus.'1 Strong evidence of a link with ovarian cm was found by Graham and Graham,12 who inje.'ad mice, hamsters, guineapigs, and Dutch rabbits with w.cmolite asbestos. The mice and hamsters showed w lesions, presumably because of a protective layer of peri toneum surrounding their ovaries which is absent in the guineapigs and rabbits. Both guineapigs and rabbits de veloped an atypical papillary pattern of ovarian epithe lial hyperplasia which the authors suggested was sirr.i :t to early ovarian epithelial tumours in women. F u r f '-:more, they observed birfringent bodies in sections o; w out of twelve ovarian tumours and none of rune nar.-.v,, controls. These bodies were thought to be ssbe;; although no rigorous proof was provided. Althu-i.f.i asbestos fibres can be demonstrated in lungs, they w difficult to identify in msothlial tumours, and tr.-vr prcsence would not be mandatory to establish an a.-w.;ation. The case against talc began as guilt by associa;:. with asbestos. Mineral talc is closely related to asbe-. and the two substances are of'en found together i i mineral deposits. The pulmonary lesions ot talc rndwrs and irnners13 were virtually indistinguishable from thu-r due to asbestos but the latent period was about 10 wears longer. Pleural and peritoneal tumours were fourni or three to four times the expected frequency until panicu late-exposure control measures were instituted in 1950 in the U.S.A. A follow-up study14 showed that these measures had returned risks to normal. An Itahu.n study15 of talc millers and miners working a deposit less contaminated by asbestiforms showed no netease lung or peritoneal tumours. Thus, epidemiological da;-', could be interpreted as showing that the risk of develop ing cancer from an occupational talc exposure was due to contaminating asbestos. EPIDE \H 0I.G G K :-\L STUDIES The epidemiological assessment of the risk due to talc is hampered by several factors. Firstly, talc exposure w so widespread that control groups are difficult to idea tify. I ale is used in dusting powders, deodorant.,, ck :'k. crayons, textiles, pills (including two of the six corr.von brands of contraceptive pills'), soap, insulating mater a.-, paints, asphalt filler, paper, and condoms and contra-,, ,-rtive diaphragms. It i-> also used exteasi'.cly in food , \ - ;*-s 350 THE LANCET, AUGUST in , i'-'7 9 cessing. ScCOIldU COU.,Uimer talc products marketed beton: 1973 wen: vari-ibi contai r,limited b; asbestos. Rorv et al.18 studi ed twent v produc ts, half of :which con tamed (detectable amount:s of trerrolite (up ito 14%. by v.eight) . Two bra ads had 1detectab! e chrysotilc fibres. In Ootobci-, 197u>, the Cosm etic, To: leery and Fragrance Associa [lull KC. 1. e A ) re'vised the ir guidelincs for talc and recommended that no sample containing asbestos detectable bv X - r a y diifraction and optical microscopy v,:Th. dispersion staining should be sold. Therefore, data collected on populations exposed before 1976 may re flect the hazard of contaminating asbestos rather than nlc. Unfortunately, adherence to the revised C.T.F.A. miiddmes is voluntary' and monitoring of samples is left to individual manufacturers; so that, even now, com mercial talcs arc not certain to be asbestos-free. Finally, the epidermologtcal 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. Netvhouse17 has reported no evidence oi health hazard among the predominantly female employees in a British talc factory in a study which needs to be continued another ten years4 to be confident in the negative result. Information from epidemiological studies of talc exposure thus far must be considered in conclusive. EXPHRIMKN TAL STUDIES Animal studies on the efFects of talc have been reviewed by Hildick-Smith.' Talc was not found to be mutagenic in vitro, but neither is asbestos.18In-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 of unde fined chemical and physical characteristics, their uni formly negative results provide the basis for HildickSmitli's conclusion, that "concern . . . about the possible health hazard from consumer exposure to cosmetic talc is unwarranted" . Yet data on the cellular response to talc are sparse. Allison19 observed that talc-- like other agents of chronic inflammation, including asbestos20-- is ingested by macrophages with attendant release of lyso somal hydrolases. Lung fibroblasts take up talc particles up to 10 jrm in diameter,21 and these particles penetrate the cell membrane but not the nuclear membrane. Chry solite asbestos fibres are handled in a similar way. No studies of the effects of talc on cell metabolism have been reported. Intratracheal instillation of talc in Syrian <*olden hamsters has been shown not to induce respira tory tumours, though fibrosis was not uncommon.22BenzoCripyrene alone also failed to induce respiratory-tract tumours.2-' However, talc and benzo(a)pyrene together induced tumours in 80% of hamsters treated. Whereas the bulk of evidence suggests that talc is not an indepen dent carcinogen, it may act as a co-carcinogen or pro moter. None of the animal studies has clarified what talc- does at the cellular level. C LIN ICA L EVIDENCE 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 talc has been used to obliterate pleural cavi ties in diseases causing chronic effusions. In a granulo matous lesion Lichtman et a l / ' found talc wbrni'. oad been, deposited there 36 years earlier. They also unv;; =-d tremendous variation m the response to talc ot aiu.-r tu tissues and the same tissue m different speces, a ne lesions developing central necrosis within five daw in the absence of a polymorphonuclear response. T.-.U: a diffuse lung disease characterised by pern .fo. fibrosis, was an occupational pneumoconiosis until -v.i.usure limits were enforced m the U.S.A. Talc bo*.ic, m sections of diseased lung, as with asbestos bud.e, m asbestosis, suggest that talc elicits a strong de;--:i ve reaction in man. Pulmonary intravascular granuwrnas caused by intravenous injection of talc-containing .rug formulations can lead to vascular thrombosis and osis with pulmonary hypertension.23 Thus, there is '.tile doubt that talc is not as inert in man as in some animal species which have been used to assert its fcem The most provocative evidence of a specific ass"C.jt.on between talc and ovarian cancer was that repored by Hcnderson et al.,26 who found talc particles 0-1-.1 ,e.e w diameter deeply embedded in 75% (10 of la) oi 'nan tumours studied, as well as some cervical and endome trial tumours. No asbestos fibres were identified. 1 nc.-r tainties about applicability of the technique used a that report have cast some doubt on the validity of the nr,cl ings, but several subsequent papers from the u.r.c group27" 31 lend weight to the original contentions. Access of talc to the peritoneal cavity is most hksfo through the vagina. Studies of the transport of ra rx le s in the human female reproductive tract'2 have that non-motde inert carbon particles deposited .re vagina can be recovered 30 to 35 min later in the 1Y.>- pian tubes. TALC AND OVARIAN CANCER We suggest that cosmetic talc can be deposited m. the vagina through repeated application to the perineum c.r through use of a talc-dusted diaphragm or condom d u r ing intercourse. As it is carried througn tne r-urmlc reproductive tract most particles are removed ay t.'.cai defence mechanisms, but an occasional particle can ce deposited on the surface of the ovary. Possibly stimu lated by gonadotrophins and/or ovarian hormones. '.Al taic (perhaps contaminated with asbestos) alters ore responsiveness of the ovarian epithelium, which ulti mately proliferates autonomously. This hypothesis seems to be consistent with the known facts about ovarian cancer. With talc cxpo-mie berinning in infancy, hormonal stimulation with menarche, and assuming a 20-40 year latency prtieu, peak incidence of ovarian cancer might be expected m the 40-60 year age group. This is, in fact, the observed age-group of peak incidence. The hypothesis would pre dict the observed high incidence of bilateralitv. It would also predict that anything interrupting the patency or the female reproductive tract should protect against ovarian cancer. An epidemiological report from the Mayo Clinic" shows that hysterectomy is associated with a lower risk of ovarian cancer. Similarly, oauer.-.-; with a history of tubal disease (e.g., scarring from p::w:c mflammatory disease) should have a lower incidence wt ovarian cancer. Although'this prediction has not own directly assessed, data suggesting a lower attack-raw m sexually active women may indirectly support the : Trif l a n c l t , A ro i.-'P : iS , 1 9 7 9 il; norob' '1 he obser, cd increased risk of ovarian cainear it. l.tte-pnrnEurous and nulb.parous women7' can be explained by implicating uninterrupted cyclical horir.i.ne*influences in the fteneMs of ovarian epithelial ncoplaaa. CONCLUSION The risk of cosmetic talc has not been fully evaluated. Enforcin'? the removal of detectable asbestos from talc is a first*step to protecting consumers from potential hazard. Investigators should focus on detecting the e-Tects of talc on cells in general and hormonally respon sive cells specifically. Primates should be used in experi mental studies because their hormonal cycles and epithe lial trophisms most ciosely parade! tnose Oi women. E'forts to identifv particles in ovarian-cancer specimens should be intensified. The epidemiological study of Xev.house and her colleagues17 in Great Britain on the risks of svstemte exposure in femaie talc workers should be repeated in another geographical location. Further more, a study on the risks of 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 natients with ovarian cancer. Data obtained from such sn ac-roach mav justify the absolution of talc wmen has al-ea-dv been claimed.7-'1 But until such information is collected The Lancet's statement that "it seems unlikely that future exposure to cosmetic talc of the specifica tions now agreed to by major manufacturers will present a health hazard''must be taken on faun alone. Rs.-ii;.-'. for reprints should be aJJressrd to R. C. Y. REFERENCES 1 T ;n 'in CH Fnolo.av of cancer of the hu-nan ovary- a review. J .Not Cr-.-cerl;,: 197-1,53: 1601--13. , ri.'ier HP Arlan R I lie. a possible occupational and environrreiuai car- cn.iven. 7 Oceup S fed 197.-, 15:9- 7 H-'e cf-Smilh G5 . ! i'-e biology of talc. Jir'j Indus: M ed 1976, 33: 2 '7-29. Aounvniou. Co>mei.cialc powder. Lancer 1977,i. 1343-9 Eraod KG, Johnson KH, Buoen LC. Foreign bojy tumongencsis. CRC C m ite-eTorreo; 1976;.',: 353-94. Doll R. M onahty inun luna cancer in asbestos woikers. h r J Indus: Men 1955, 12:51-6. Wa.-ner JC Slegss CA, M archand P. Diftuse pieural mesointlioma and Vibestos 'erpofTre in N orth Western Cape Province. Br J Indus: M ed 1906.17i 260--71 . K '3 lc E \bcs<rsibarniiWormnalnopUsm*. Lancet 19o0,n* 1211-6. Ntv.hou>c M L, Bern* G, V agner JC, Turo'< ME. A siudy of the mortality of femaie a>be-Uu* workers B rjir.d u sx Med 1972; 2 9:134-41 . _ \ n a n a N I, Polan AK. Son-occupittQjtal exposure to asbestos and malignant rr.oothehoma in female- L znret 193; L 1061-3 .W a rn e r JC, Berry G Mesotheliomas in rats following inoculation with asbev.os. B r j Cncer 1969; 23: 567-1 G rd h an J, Graham R. O varian cancer ar.J asbestos. Environ fes 1967; 1: 115 - 2 . , K or/eld M, Messne J, Kooyman O, Zuki MH. Mortality among talc miners ''d mdlers m New York State. Arch Environ Health 1967; 14; 663-7. K!-p!=j M, Messite j , Zaki M H Mortality experiences of talc workers' a iV.u-v-vp stud) j O .cup M ed 197-1, 15: 345-9 R .bm o G r, Star.scm G, Piolauo G, Romano CA. M ortality study of talc miners and milled j O ccupM ed 1975; 13:186-93. , Rohl \N , L an ier AM, Sehkoif IJ, ei al. Consumer talcums and powders- r-meral anJ^cheTucal characterization. J Toxicol Environ Health 1976, 2 :255-S4. ' \e ML, Miner BF, Moore V/KS Paper given at seminar on Biology of Talc to I le a ln Products, Card'.rt, May, 1976, cited m 5. \-r,cN 'BN unpublished observations. \C. Ps vemmar on F.ioloov of Talc m Health Products t ird in , Mav, 19"6. Srhoriet-rner H I D i n a P, Hyl-cm w . G ug* M, Allison AC 1 he selective r.-.eise of l.bOiOrn.d ,7CiJ hydrolases Irom mouse peritoneal mocrophjites bs -limuli of cn-.imc inflammation. r> j Eep Pa:hel 1977, 5S: 3 1 i-2 6 . , V, J, R'unde'l G, Richards R, el al Ingestion of laic particles by cui I.r.-'.i !an Vf c ro b fi'li E n f r c r R e s 1975; 9: 173-8. Strr.-'CV F, U oaiand I. Role ot talc and Feniodi pyrene in respiratory cm ,--fo m jl'O n S - S e J ] R e s p n D u : 7 3 ; 59: 130-40 23 K u.chrer.M The J B urn, Amberso.I leCurc ihe cause o fljin . cat Re: R e.prD .sP InS, St: 573-9/. , 24. l-ichiiiun Al.. McDonald JR, l - W CA . 1 C F;" - (r. nseoiU >: 1946, 53: 531-5S. , 25 ll opbns GB, 'I ltl.ir CD. l'uhnoiury u lc gtnniiloinatoMS . I n ,, - iJ-aWTO, lD M 'J -- s -- . ., , 26 Henderson W'J, jo d .n CAF, Turnbull A u, Grn.Uhs K. faic and a ..i o f the ovary and cervix J Ob.u: Csr.ueol B ' Cor-n 14, i , 27 Henderson \\ j The use of analytical electron m icrocopy in the s m -. eiyn and nar.iritiy ticcurr'ng aur.era's in luol-irca' tissues. A lie-.- 78 Growths K, Henderson WJ, Chandler JA, Jo-hn C \i : 0*..,-an some new on.ilytica! aporoaJies P.Mdr.-J \! e c j 19.j , 4 9 :oV -,'- 29. Henderson Vv , Chandler JA, Elunde'.l G, Gr.fnths C, D a.ies JO. 2 e cation of analytical electron microscopy to me study o: disetsed tissue j Hiero,-spy 1973; 99: 133-92. 30 H end.rasn WJ, Gnrths K. Identification of panicles u: osaran i.s .. Brush MG*, Tavior RW, cds Gynvcological mahgnaPk.> c u r... tx ^ n m c m l studies. 8.Uima: V.illUm- and `A 1575 225--. 31 HcnJcrson W }, Hamiiton TC , GnK'ih> K. Talc i.x normal asid m.a. ova. tan ttsyac. Lancet 19 '9, i 499. i 32 Egh GE, Newton M. T he transport u f carbon paciwdcs u\ tnc rutnao ^reproductive tract. Terr.!Seen! \ 9 6 1; 12; 151-5 33 Alineases )P, Strom H, IKcScer DG. Dauheriv MB, O'oalion MM . cancer, mcid'-rcc and ^asc-cont-'oi study. Can.Ler 19,9: 4 j : / -> -, 34 Peral V, Fraser I', Chitvers C. Dees pregnancy protect s.?am.t . Round the World fro re our Correspondents United States THE PUBLIC'S RIGHT TO KNOW If there is one thing that distinguishes the U S. irom .n= U.K. i: is the publicity that surround crimes and t. accused of committing them. In Britain the discussion. ... media of sub-judice matters is sharply circumscr.bcd. ha ; .c U.S. comment has been very free, far too free some ....... . argue. In a notorious or scandalous case there uMG ,e mous publicity on every aspect, including every detail >1 ' -e accused, before the case ever: comes to tnau ^.ul . defended by the media as part of the public's nght to .m, embedded in that sacrosanct document, the U.S. Lonstitui...... But the Supreme Court has been busy in these mu weeks It decided in the Weber case that affirmative action -m -. permitted in favour of minorities, the victims of in e q u ity the past, even if other racial groups were thereby disaGvm taved The case differed from the Bakke case m that no ueec'.rn- quota was involved. The Court ordered extensive "b u s-tv ;' m enforce racial balance in schools (though whether tne le d wu be available--or well spent-- is another matter!. F a ith /, to the furv of the media and the libertarians the Court aecureo., by a majority, that a judge, if both sides agreed, could exeme : the Press and other media from the courts in criminal arm ... m cases. The judgment came, as so often happens, com a , lively trivial legal fracas in New York State. But, by implica tion,' it could have extensive repercussions. Justice, it us s.,id. may certainly be done, but it certainly will not be seen to done under this dispensation, and the public will not know, we can expect considerable hubbub to develop over this diciHon^ The public right to know has been in the foreground am.'-- the Watergate affair, when the public were denied this ngm -y deliberate concealment. It led to the Freedom Ot Infor.. at.:,.. Law by which public access to all Government document-. now permitted. In theory this is admirable, and u o r r : .. fingers are pointed at Britain, where so much secrecy pre--' '1 There are also some undesirable aspects which are now ceir \ to the fore, particularly those involving the F.B.I. and -r-i.Mr archives. Every little crook and nanny, as it weie, is searthm. every little nook and cranny of these archives (of course, -t taxpayers' expense) for something or other. Some a,e or., for the names of those who informed on them to tne ponce or betrayed Party comrades; others are looking for opporiu.n.c>ex