Document zdEozdR6qgvj9Q2mkvyKkXrR7

CCS STIC TALC POOLER From time inirasmor+al Kan, like his evolutionary rreciece ssors, has neon exposed to airborne dusts. Such, exposure is-a 'corollary of living and survival. Not unexpectedly, therefore, the lungs have efficient naans of clearing themselves of inhaled particles and a functional reserve such that the accumulation of uncleared dust may be considerable before there is any obvious loss of work-capacity. However, it has long been recognized that heavy exposure to dusts, such as quartz and asbestos, may lead to loss of function and in the case of asbestos, to cancer of the pleura and of the lung itself.- The realization that even casual exposure to asbestos may be associated with, increased risk of mesothelioma, presently occurring at the rate of nearly 200 new cases a year in the United Kingdom1 , has brought into question the safety of othc-r coruaon dusts such as cosactic talc. There are two sain concerns: firstly that the inhalation of a c i - - v.ill cause loss of function through fibrosis or emphysema and secondly that it will predispose to cancer. Although known to be capable of giving rise to granulo.uata when introduced into the tissues or body cavities 2 , it has hitherto been widely assumed that exposure to cosmetic talc does not predispose to pulmonary fibrosis, hcv.evor, -_.:a fact that no association has been scon betweon the use ci talc and loss of lung function night theoretically be simply a reflection of the lack of nations sensitive enough to detect losses of function that are smsll compared with those due to smoking ar.d other factors and to heterogeneity in Dii-ar.tritypsin status. For sir.-.ilnr rc-:-;u.'.s any effect of talc exposure on cancer incidence is unlikely to have been noticed without deliberate study. Until recent years facilities for Studying the long tern effects of inhalation of dusts in laboratory animals have boon ir. short supply and even now the r.r.ii':r.t1vo val iia n-r ?rv-;on"i rrnrji*1s i-s o-.Tnfli:: f. Tmvc Aven -in t.lin J&J-0098692 JNJ 000038318 ? case of tobacco stioke, where the/hazard to humane is indisputable, it >A has proved difficult or impossible to duplicate the effect in laboratory animals by the inhalation route 3 , although, in the case of inhaled 4 asbestos .dust, positive results have been reported in animals Historically, the possibility that talc causes cancer dramat ically, if unfortunately, bit the headlines of the daily press when workers in Cardiff s reported finding talc particles in cancers of the ovary and uterine cervix. The report was greeted with scept icism particularly because the particles were not positively ident ified as talc, their presence did hot prove causation and it was very possible that they had found their way on th sections ns a result of contamination of tissues after removal from the body. Subsequent 6 cr/.orai analysis failed to confirm that the particles were talc and the passage of six years without the publication of confirmatory evidence suggests the early scepticism was well founded. A meeting of talc powder manufacturers and independent scientists took place at Cardiff during Kay 1975 under the chairmanship c? Dr. J.C. Gilson, Director of the nodical Research Council's Pneumoconiosis Research Unit. At that meeting the toxicology of talc was reviewed and the need for further information discussed. `The review was facilitated "by a survey of the available literature urovided by Dr. G.Y. t Hi 1cick-Sr;ith . Assessment of toxicity necessarily starts with a consideration 01 the physical and chemical specifications of the test material, and this, unfortunately, is also where much of the assessment ends in the case of cosmetic talc because most of the published literature - epidemiological, clinical and experimental - concerns exposure either to industrial talcs that are variously contaminated with minerals known to be hazardous or to talc of undefined physical ana chemical characteristics. ^ J&J-0098693 JNJ 000038319 The long thin fibrous shape of asbestos particles enables them to be carried more deeply into the lungs than spherical particles of similar mass. The fact that the normally effective clearance mechanisms have difficulty in coping with relatively large, long thin particle's deposited deeply in the lungs is an important determinant of the hazards from asbestos dust. Geologically, talc (which is nominally a hydrated magnesium silicate) and certain amphiboles - tremoite, actinolite and anthophyllite - may occur in juxta position and consequently talc may be contaminated with these minerals. Apart from this, talc may contain chlorite, quartz, carbonates, such as calcite, dolomite and magnesite, and occasionally other minerals in lesser amounts. During the last few years, major cosmetic -manufacturers in the United Kingdom and the United States of America, as represented by the Toilet Preparations Federation and the Cosmetic, Toiletry and Fragrance Association, respectively, have evolved specifications for cosmetic talc which ensure the . , . , 7, 8, 9 and 10 virtual absence of fibrous amphiboles At present there is no direct statutory control of the quality of cosmetic talc in any country and it is debatable whether such control is necessary to bring minor manu facturers into line with the standards now adoptod by the major firms. The presence of fibrous particles in talc reduces its free flow and lubricity, thereby rendering it less cosmetically desirable. Such contamination is thus self-limited. More importantly, however, is the fact that the fibrous J&J-0098694 JNJ 000038320 materials most likely to contaminate talc which Tail to comply with the specifications referred to above, namely, tremolite, anthophyllite and actinolite, are not those most clearly associated with carcinogenic hazard (i.e, crocidolite, amosite and chrysotile). Furthermore, it would be sensible to consider what controls, if any, are necessary for talc as used in foods and medicines, before introducing legislation specifically in relation to cosmetic talc. It is arguable that, if the inhalation of particles of amphibole and silica-contaminated talc dust were found to be harmless, it could reasonably he assumed that talc free from these materials iB ssfe. Kleinfeld and his colleagues have studied the incidence of cancer and respiratory diseases in talc miners and millers in New fork State. The talc concerned which is V> t-' f t v heavily contaminated with^amnhiboles and free silica was initially reported to be associated with an increased mortality from mesothelioma and cor ii pulmonale . Later the snmo_workers reported that men employed in the mine after dust levels had been reduced, had death rates from malignant diseases that were similar it- to those for white males in the U.S.A. generally i3 Also in the U.S.A., Fine and his colleagues have reported a higher prevalence of productive cough and chronic obstructive lung disease among rubber "workers exposed to a non-fibrous industrial grade talc -erfc- J&J-0098695 JNJ 000038321 5 - than among control workers. . From their data they calculated that 3 a safe exposure level would have been 0,24 tng/m mass respirable particulate talc ae a time weighted averogo. In Italy, Rubino and his colleagues ^ compared the spectra of causes of death among talc miners, talc millers and agricultural workers. The talc miners were exposed to dusts containing .596 silica at levels far in excess of threshhold limit value. Significantly more of them than of the controls died from respiratory disease, "but death rates from all'forms of cancer, including lung cancer, were significantly lower among the miners than among. the controls. By contrast, among the talc mlllerB, exposed to dusts containing 0.05J, silica, but no detectable asbestos, at concentrations of 20 million p a r t i c l e G per cubic foot, there was no excess of deaths from pulmonary disease or cancer of any site compared with the control group. The deficit of lung cancer among the talc miners is plausible in so far as a similar deficit of lung cancer among coal I** miners seems to tie real * An on--going study of over 5200 persona, mainly women, at a factory in Britain where cosmetic talc has been made and packed for over 5 0 years, has so far revealed no evidence of it health hazard , but follow-up would need to continue for at least a further decade before one could be confident of a negative result. Other less informative epidemiological studies are reviewed by t Bildick-Smith J&J-0098696 JNJ 000038322 Most studies in animals suffer the deficiency that the quality of the talc used wae not specified. An exception '7 is a recent report by Wehner and others who studied the effects in hamsters of repented exposure to aerosols of cosmetic talc up to total doses of respirable particles equal to nearly 2000 times those received by humans using cosmetic talc during baby care. Exposure had no adverse effect on body weight, survival, incidence of pathological changes In the respiratory tract or incidence Of ' neoplasia at any site. Another exception is the report by Wagner and his colleagues who saw no mesotheliomas in 4-.8 rats after the intrapleural administration of cosmetic talc, whereas 18 out of 4-8 rats similarly exposed to chrysotile asbestos developed Buch tumours. The same workers exposed rats to c o s m e t i c talc by the inhalation route on five days a week for up to 1 year. At the highest level of exposure " about three times that studied by Wehner and his colleagues ^ - there was elightly more pulmonary fibrosis than in controls, but no meaningful excess of pulmonary neoplasms. A number of l'ess .rolevant animal studies, all of which give negative results for carcinogenicity, aro reviewed by Hildick- Smith . In summary, there are at present no grounds for believing that normal consumer exposure to cosmetic talc has in the past led either to cancer at any site or to measurable loss of lung function. A fortiori, it seems unlikely that future exposure to cosmetic talc of the specifications now ngrood to by major manufacturers will present a health hazard. J&J-0098697 JNJ 000038323 REFERENCES Greenberg, M. and Lloyd Davies, T.A. Brit. J. Induatr. Med., , 91, 1974. Bluemel, G. , Piza, F. and Zischka-Konorsa, W. Wiener K l i n . Wpchschft., ? 4 , 12, 1962. Davis, B.R., Whitehead, J.K., Gill, M.E., Lee, P.N., Butterworth, A.D. and Roe, F.J.C. Brit1. J. Cancer, 31, 469, 1975 Wagner, J.C., Berry, G . , Skidmore, J.W. and Timbrel!, V., Brit. J . Cancer, 2.9, 2^2, 1974. Henderson, W.J., Joelin, C.A.F., Turnbull, A.C. and Griffiths, K., J. Obstet. Gynaec. B r . Cmwlth., 7 8 , 266, 1971 Hildick-Smith, G.Y., Brit. J. Indust. Med.. 55, 217, 1976. Toilet Preparations Federation Ltd. Cosmetic Tale; issued 1977 Specification No. 12: C.T.F.A. Specification. Talc, Cosmetic, The Cosmetic, Toilet^pand Fragrance Association, Inc., Issue 10-7 1976. Toilet Preparations Federation Ltd. Cosmetic Tale, issued 1977 Analytical Method 77: Hamer, D.H., Rolle, F.R. and Schelz, J.P., Aroer. Pndust. Hyr-*. Assoc. J., ??, 296, 1976. Kleinfeld, M., Messite, J., Kooyman, 0. and Zaki, M.H., Arch. Environ. Hlth., 1 4 . 6 6 J , 1967- Kleinfeld, M . , Messite, J. and Zaki, M.H., J- Qccup. Med,, 1 6 . 34^, 1974. Fine, L.J., Peters, J.M., S ^ b-.s <5. Archives of Environ. Health, 51 195 , 1976. i-~T' J&J-0098698 JNJ 000038324 Rubino, G., Scansetti, G., Piolatto, G. and Romano, C., J. Occup. Wed., 1 8 , 186, 1976. Goldman, K.P., Brit. J. Ind. Med.. 22, 72, 1967. Newhouse, M.L., ?rtiller, B.P. and Moore, W.K.S., Unpublished contribution to Seminar "Biology of Talc used in Health Producta", Cardiff, Wales, May 1976. W e h n e r , A.P., Zwic)cei j C.M., Cannon, W.C. , Wateon, C.R. and Car] ton , W.tf. F d . Cosmet. Toxicol., 1 9 . 121, 1977. Wagner, J.C., Berry, G., Cooke, T.J., Hill, n.j., and Skidmore, J.Vf., Animal Experiments with talc in Proceeding of 4th International Symposium on Inhaled Particles and Vapoura. Edinburgh, 1975. l-o- ho-=puhl3hed. . t'Tl . J&J-0098699 JNJ 000038325