Document 8bG5v9QMqMEp5BEVr5KYaNoZ

1348 THE LANCET, JUNE 25, 1977 subjects, whether manifest in the fasting or in the stimu lated state, is independent of coexisting obesity and glu cose intolerance although both are often contributory factors. Which is chicken and which is egg is unresolved but experimental evidence favours a causal role for hyperinsulinaemia. Long-continued administration of in sulin to animals in supra-optimal doses can give rise to histological and biochemical lesions resembling those of human atheroma13 and insulin encourages the synthesis of cholesterol and other lipids by arterial-wall tissue14'15 both in vivo and in vitro. Of the many factors known to cause exaggerated insulin secretion some, such as obesity and high sucrose consumption,16 have been implicated, on epidemiological grounds, in the pathogenesis of ath erosclerosis whilst others, such as increased consumption of sugary alcoholic drinks,17 have so far not been. Con versely, certain types of vegetable fibre, the exclusion from the diet of which have been claimed to increase the risk of atheroma,18 reduce the immediate and overall in sulin secretory response to ingested carbohydrate19with out adversely affecting glucose tolerance. The role of the insulinotropic gastrointestinal hormones in providing the link between composition of the diet and the hyperinsulinaemia of atherosclerosis is undetermined and awaits investigation by the newer methods of measuring them in blood. COSMETIC TALC POWDER Fr o m time immemorial man, like his evolutionary predecessors, has been exposed to airborne dusts. Such exposure is a corollary of living and survival. Not unex pectedly, therefore, the lungs have efficient means 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 recognised 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 observation that even casual exposure to asbestos may be associated with increased risk of mesothelioma, now occurring at the rate of nearly 200 new cases a year in the United Kingdom,1 has brought into question the safety of other common dusts such as cosmetic talc. There are two main concerns. Firstly, will inhalation of a dust cause loss of function through fibrosis or emphy sema? And, secondly, will it predispose to cancer?102*456789 10. Sloane, J. M ., Mackay, J. S., Sheridan, B. ibid. 1970, ii, 586. 11. Kaskyap, M. L., Magill, F., Rojas, L., Hoffman, M, M. Can, med. Ass. J . 1970,102,116512. Stout, R. W., Bierman, E. L., Brunzell, J. D. in Diabetes: its Physiological and Biochemical Basis (edited by J. Vallance-Owen). Lancaster, 1977. B . Stout, R. W. Br. med.J. 1970, iii, 685. 14. Stout, R. W. Lancet, 1969, ii, 467, 15. Stout, R. W., Buchanan, K. D., Vallance-Owen, J. Atherosclerosis, 1973, 18, 153. 16. Szanto, S., Yudkin, J. Postgrad. m ed.J. 1 9 6 9,45,602. 17. O'Keefe, S. J. D., Marks, V. Lancet, June 18,1977, p. 1286. 18. Cleave, T. L. The Saccharine Disease. Bristol, 1974. 19. Jenkins, D. J. A., Goff, D. V., Leeds, A. R., Alberti, K. G. M. M ., Wolever, T. M . S., Gassull, M. A., Hockaday,T. D. R. Lancet, 1976,ii, 172. 1. Greenberg, M., Lloyd Davies, T. A. Br. J. ind. Med. 1974, 31, 91. Although talc can cause granulomas when introduced into the tissues or body cavities,2 exposure to cosmetic talc has been widely assumed not to predispose to pul monary fibrosis. However, the fact that no association has been seen between the use of talc and loss of lung function might simply reflect the lack of methods sensi tive enough to detect losses of function that are small compared with those due, for example, to smoking and to heterogeneity in a,-antritypsin status. For similar rea sons any effect of talc exposure on cancer incidence would probably escape notice unless deliberately sought. Until lately facilities for studying the long-term effects of inhalation of dusts in laboratory animals have been scarce, and even now the predictive value of animal models is questionable. Thus, even in the case of tobacco smoke, where the cancer hazard to man is indisputable, duplication of the effect, by the inhalation route, in laboratory animals has proved difficult or impossible,3 although inhaled asbestos dust has given positive results in animals.4 The possibility that talc causes cancer dramatically hit the headlines of the daily Press when workers in Car diff5 reported finding talc particles in cancers of the ovary and uterine cervix. The report was greeted with scepticism because the particles were not positively iden tified as talc, because their presence did not prove causa tion, and because they might have found their way onto the sections as a result of contamination of tissues after removal from the body. Subsequent mineral analysis failed to confirm that the particles were talc6 and the passage of six years without publication of confirmatory evidence suggests that the early scepticism was wellfounded. A meeting of talc-powder manufacturers and independent scientists took place at Cardiff during May, 1976, under the chairmanship of Dr J. C. Gilson, direc tor of the Medical Research Council Pneumoconiosis Unit. At that meeting the toxicology of talc was reviewed and the need for further information discussed. Assessment of toxicity necessarily starts with a consider ation of 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 reports-- epidemiological, clinical, and experimental-- concern exposure either to industrial talcs that are variously contaminated with minerals known to be hazardous or to talc of undefined physical and chemical characteristics. 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 large, long thin particles de posited 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-- tremolite, actinolite, and anthophyllite-- may occur in juxtaposition and consequently talc may be contaminated with these minerals. Apart 2. Bluemel, G., Piza, F.s Zischka-Konorsa, W. Wien, klm. Wschr, 1962,74,12. 3. Davis, B. R., Whitehead, J. K., Gill, M. E., Lee, P. N., Butierworth, A. D., Roe, F. J. C. B r.J. Cancer, 1975, 3 1 ,469. 4. Wagner, J. C., Berry, G ., Skidmore, J. W,, Timbrell, V. ibid 1974, 29,252. 5. Henderson, W. J,, Joslin, C. A. F., Turnbull, A. C., Griffiths, K. J. Ohsut. Gyncec. Br. Commotm1. 1 9 7 1 ,7 8 ,2 6 6 . 6. Hildick-Smilh, G. Y. Br.J. ind. M ed. 1976,33,217. THE LANCET, JUNE 25, 1977 from this, talc may contain chlorite, quartz, carbonates (such as calcite, dolomite, and magnesite), and occa sionally other minerals in lesser amounts. During the past 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, have drawn up specifications for cosmetic talc which ensure the virtual absence of fibrous amphiboles.78910*234' 10 At present there is no direct statutory control of the quality of cos metic talc in any country and it is questionable whether such control is necessary to bring minor manufacturers into line with the standards now adopted by the major firms. The presence of fibrous particles in talc reduces its free flow and lubricity, thereby rendering it less cosmeti cally desirable. Such contamination is thus self-limited. More important, however, is the fact that the fibrous materials most likely to contaminate talcs which do not comply with the specifications-- namely, tremolite, anthophyllite, and actinolite-- are not those most clearly associated with carcinogenic hazard (crocidolite, amosite, and chrysotile). Furthermore, it would be sen sible to consider what controls, if any, are necessary for talc as used in medicines, before introducing legislation specifically in relation to cosmetic talc. If the inhalation of particles of amphibole and silica contaminated talc dust were found to be harmless, one might reasonably assume that talc free from these materials is safe. Kleinfeld and his colleagues have stu died the incidence of cancer and respiratory diseases in talc miners and millers in New York State. The talc con cerned, which is heavily contaminated with both amphi boles and free silica, was initially reported to be associ ated with an increased mortality from mesothelioma and cor pulmonale.11 Later the same workers reported that men employed in the mine after dust levels had been reduced had death-rates from malignant diseases that were similar to those for White males in the U.S.A. generally.12 Also in the U.S.A., Fine and his colleagues13 have reported a higher prevalence of productive cough and chronic obstructive lung disease among rubber workers exposed to a non-fibrous industrial-grade talc than among control workers. From their data they cal culated that a safe exposure level would be provided by a threshold limit value of 0'25.m g/m 3 mass-respirable particulate talc. In Italy, Rubino and his colleagues14 compared the spectra of causes of death among talc miners, talc millers, and agricultural workers. The talc miners were exposed to dusts containing 5% silica at levels far in excess of threshold limit value. Significantly more of them than of the controls died from respiratory disease, but death-rates from all forms of cancer, includ ing lung cancer, were significantly lower among the 7. Toilet Preparations Federation Ltd., specification no. 12: Cosmetic Talc. 1977. 8. C.T.F.A. Specification: Talc, Cosmetic. Cosmetic, Toiletry and Fragrance Association, Inc., issue 10--7 .1 976. 9. Toilet Preparations Federation Ltd., analytical method 77: Cosmetic Talc. 1977. 10. Hamer, D. H.} Rolle, F. R., Schelz, J. P. Am. ind. Hyg. Ass. J. 1976, 37, 296. 11-Kleinfeld, M., Messite, J., Kooyman, O., Zaki, M. H. Archs envir. Hlrh, 1967, 14, 663. 12. Kleinfeld, M., Messite, J., Zaki, M. H.J. occup. Med. 1974,16, 345. 13. Fine, L. j ., Peters, J. M., Burgess, W. A., Di Beradinis, L. J. Archs envtr. H lth, 1976,31, 195. 14. Rubmo, G,, Scansetu, G.> Piolatto, G., Romano, C. J . occup. Med. 1976,18, 186. 1349 miners than among the controls. By contrast, among the talc millers, exposed to dusts containing 0-05% silica, but no detectable asbestos, at concentrations of 20 mil lion particles per cubic foot (27 litres), 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 miners seems to be real.13 A continuing study o f over 3200 per sons, mainly women, at a factory in Britain where cos metic talc has been made and packed for over fifty years, has so far revealed no evidence of health hazard,16 but follow-up would need to be extended for at least a further decade before one could be confident o f a nega tive result. Other less informative epidemiological stu dies are reviewed by Hildick-Smith.6 In most of the work in animals the quality of the talc has not been specified. An exception is a report by Wehner and others17who studied the effects in hamsters of repeated 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 dur ing baby care. Exposure had no adverse effect on bodyweight, 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,18 who saw no mesotheliomas in 48 rats after intrapleural administration of cosmetic talc whereas 18 out of 48 rats similarly exposed to chrysotile asbestos acquired such tumours. The same workers exposed rats to cosmetic talc by the inhalation route on five days a week for up to a year. At the highest level of exposure -- about three times that studied by Wehner and his col leagues17-- there was slightly more pulmonary fibrosis than in controls, but no substantial excess of pulmonary neoplasms. A number of less relevant animal studies, all of which gave negative results for carcinogenicity, are reviewed by Hildick-Smith.6 In summary, there is no reason to believe that normal consumer exposure to cos metic talc has in the past led either to cancer at any site or to measurable loss of lung function. It seems unlikely that future exposure to cosmetic talc of the specifications now agreed to by major manufacturers will present a health hazard. H/EMOPHILUS ENDOCARDITIS Hcemophilus endocarditis is rare. Until lately the pub lished reports were small-scale and conflicting; now three substantial and independent investigations have been reported from the United States.1-3 15. Goldman, K. P. B r.J. ind.M ed. 1 9 67,22,72. 16. Newhouse, M. L., Miller, B . F., Moore, W. K . S. Paper given at seminar on Biology o f Talc Used in Health Products, Cardiff, May, 1976. 17. Wehner, A. P., Zwickei, G. M., Cannon, W. C., Watson, C. R. Carlton, W. W .FdCosmec. Tox. 1977,15,121. 18. Wagner, J. C., Berry, G ., Cooke, T. J., Hill, R. J., Skidmore, J. W. in Pn>- ceedings o f Fourth International Symposium on Inhaled Particles and Vapour. Oxford, 1977. 1. Geraci, J- E,, Wilkowske, C. J., Wilson, W. R., Washington, J. A. M ayo Clin. Proc. 1977,52,209. 2. Chunn, C. j ., Jones, S. R., McCuichan, J. A., Young, E. J., Gilbert, D. N. Medicine, Baltimore, 1977,56,99. 3. Lynn, D, J.} Kane, J. G., Parker, R. H. ibid. 19 7 7 ,5 6 ,1 1 5 . Dr. Francis J. C. Roe D.M'COxon.). D.Sc.|Lond.), F.tt. . Parti Coreulitm in Toxicology aotf AOtiser in Eipcrimcnul Pnbolsmr cod Concor Rcturch H ome Address 19 ManyaLRoad, Wimbledon Common. London, SWI 5HB Tel 01-946 4518 VAT Reg. No. 216 7350 73 Office 4 Kings Rpad Wimbledon London, SW19 8QN Tel 01-542 3013 FJCR/SR 14th June, 1977 Dr. Gavin Bildick-Smlth, Director, Medical Affairs, Johnson and Johnson, New Brunswick, N.J. 08903, .1 USA. Dear Gavin, Herewith a copy of what I have sent to the Lancet. I felt I had to shorten it. I will let you know the reaction of the Journal. Sincere thanks for your help. With best wishes. Yours sincerely, Francis J.C. Roe ! i! i Ene P.S. Thank, you for your letter of 9th. June. 1 have taken into account your two points on the original p. 8 (now p. 6) in a slightly different way from that proposed by yourself - But I think I have met your two points. J&J-0098691 JNJ 000038317 CCSSTIC TALC POTOER Iron tirse i-.tna^orisl rian, l i k e b i s e v o lu tio n a r y predecessors, has been exposed to airborne d u sts. Such exposure i s - a c o r o lla r y of l i v i n g and s u r v iv a l. Not unexpected!?/, t h e r e i o r e , the lungs have e f f i c i e n t rie&jis o f c l e a r i n g t h e m s e l v e s o f i n h a l e d p a r t i c l e s and a f u n c t i o n a l . r e s e r v e such t h a t th e a c c u m u la t io n o f u n c le a r e d d u s t m3y be considerable before- there is any obvious lo s s of w ork -cap acity. However, i t has lo n g been recognized th a t heavy ex p o su re t o d u s t s , such a s Quartz and a s b e s t o s , may le a d t o l o s s o f f u n c t io n and in the c a s e of a s b e s t o s , t o cancer c f the p le u r a and o f the lung i t s e l f . - The r e a lisa tio n that even casual exposure to asbestos nay be a sso c ia ted with, in creased r is k of m esotheliom a, p r e s e n t l y o c c u r r i n g a t t h e rate of nearly 200 new cases a year in the United Kingdom-, has brought in to question the safety of ether common dusts such as cosmetic talc. There arc- two sain concerns: firstly that the inhalation of a 6- - z will 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.mata when introduced into the tissues or body cavities 2 , it has hitherto been widely assumed that onposuro to cosmetic tale coos not predispose to pulmonary fibrosis, however, -_.:c fact that no association has been soon botweon the use cl talc and loss of lung function night theoretically bo simply a reflection of the lack of methods sensitive enough to detect lossos of function- that are snail compared with those due to smoking ar.d other factors and to heterogeneity in D;,-antritypsin status. For si.tila;- reasons any effect cf tale 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 been ir. short supply and even now the nr.if:-; r.:.:vn vr.l n.-* r-f an-innl mnn.^1 s i s t h u s ^vpn in t h e J&J-0098692 JNJ 000038318 T Ca *\Cj / cc.se of tobacco smoke, where tho/hazard to humane is indisputable, it has proved difficult or impossible to duplicate the effect in laboratory animals by the inhalation route 3 , although, in the case of inhaled asbestos dust, positivo results have bocn reported in animals 4 Historically, the possibility that talc causes cancer dramat ically, if unfortunately, hit the headlines of the daily press when workers in Cardiff reported finding talc particles in cancers of tho ovary and uterine cervix. The report was greeted with scepticisa 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 as a result of contamination of tissues after removal iron the body. Subsequent 6 ci/.oral analysis failed to confirm that the particles were talc and tho passage of six years without the publication of confirmatory evidence suggests the early scepticism was well founded. A m eetin g o f t a l c powder m anufacturers and in d e p e n d e n t s c i e n t i s t s t o o k p l a c e a t C a r d i f f d u r in g May 197S under the chairmanship o f Dr. J.C . G ilso n , D ir e c to r of the Medical Research C ouncil's Pneumoconiosis Research U n it. At th a t m eeting the t o x ic o lo g y of t a l c was review ed and th e need f o r f u r th e r in fo rm a tio n d is c u s s e d . The r e v ie w was f a c i l i t a t e d by a su rv ey o f the a v a ila b le l i t e r a t u r e provided by Dr. G.Y. liild ick -S rith . Assessment of to x ic ity n ecessa rily s t a r t s w ith a c o n s i d e r a t i o n of th e p h y s i c a l and chem ical s p e c i f i c a t i o n s o f th e t e s t m a t e r ia l, and t h i s , u n f o r t u n a t e l y , i s a l s o where much o f t h e a s s e s s m e n t ends i n t h e c a s e o f c o s m e t i c t a l c b e c a u s e most of the p u b lish e d l i t e r a t u r e -- e p id e m i o lo g ic a l, c l i n i c a l and experimental - concerns exposure eith er to in d u stria l ta lc s that are v a rio u sly contaminated with m inerals known to be hazardous or t o t a l c of u n d e fin ed p h y s i c a l and ch em ical c h a r a c t e r i s t i c s . ^ J&J-0098693 JNJ 000038319 The lo n g t h i n f i b r o u s shape o f a s b e s t o s p a r t i c l e s en a b les them to be c a r r ie d more d e e p ly i n t o th e lu n g s than sp h erica l p a r t ic le s o f sim ila r mass. The f a c t th at the norm ally e f f e c t i v e clearance mechanisms have d iffic u lty in coping with r e la tiv e ly la rg e, long th in p a r tic le s d ep osited d eep ly in the lungs i s an im portant ' determinant of the hazards from a sb esto s d u st. G eologically, ta lc (which is nominally a hydrated magnesium s i l i c a t e ) and c e r t a i n a m p h ib o les - t r e m o l i t e , a c t i n o l i t e and a n t h o p h y l l i t e - may o c c u r i n j u x t a p o s i t i o n and c o n s e q u e n t l y t a l c may be c o n ta m in a te d w it h t h e s e m i n e r a l s . Apart from t h i s , t a l c may c o n t a i n c h lo r ite , q u a r t z , c a r b o n a t e s , su ch as c a lc it e , dolom ite and m a g n e s ite , and o c c a s i o n a l l y o th e r m in e r a ls i n l e s s e r a m o u n t s . During th e l a 3 t f c v y e a r s , m a jo r cosmetic manufacturers i n th e U n ite d Kingdom and t h e U n ited S ta tes of America, as represented by the T o ile t P re p a r a tio n s F e d e r a tio n and the C o sm etic, T o i l e t r y and Fragrance A s s o c i a t i o n , r e s p e c t i v e l y , have e v o lv e d sp e c ific a tio n s for cosm etic t a lc which ensure the v i r t u a l, a b s e n c e o f f i b. r o u s a m p, h i, b o, le s 7 , 8 , 9 a n d 10 At p r e se n t th e r e i s no d i r e c t s t a t u t o r y c o n t r o l o f th e q u a lit y of co sm etic t a l c .in any country and i t i s debatable whether such control is necessary to bring minor manufacturera into line with the standards now adopted by the mnjor f i r m s . The presence of fibrous particles in talc reduces its free f lo w and l u b r i c i t y , t h e r e b y r e n d e r i n g i t l e a s c o s m e t i c a l l y d esira b le. Such contam ination i s thus s e lf - li m it e d . Kore im p o r ta n tly , how ever, i s th e f a c t t h a t th e f i b r o u s J&J-0098694 JNJ 000038320 m a teria ls most l i k e l y to contam inate talc which f a i l to comply w ith the s p e c if ic a t io n s refe rred t o a b o v e , n am ely, t r e m o l i t e , a n t h o p h y l l i t e and a c t i n o l i t e , are not th ose most c le a r ly a sso c ia ted w ith carcin ogen ic hazard ( i . e . c r o c i d o l i t e , a m o site and c h r y 6 o t i l e ) . Furthermore, it would be s e n s i b l e t o c o n s i d e r what c o n t r o l s , i f any, are n e c e s s a r y f o r t a l c as used i n fo o d s and m edicines, before introducing le g is la tio n s p e c ific a lly in rela tio n to cosmetic ta lc . It is arguable th a t, i f the in h alation of p a r tic le s o f am p h ib ole and s i l i c a - c o n t a m i n a t e d t a l c d u s t w ere found to be harm less, i t could reasonably be assumed th a t t a l c fr e e from th e s e m a te r ia ls iB s a f e . K le in f e ld and h i s c o l l e a g u e s have s t u d ie d th e in c id e n c e of c a n c e r and r e s p i r a t o r y d i s e a s e s i n t a l c m in ers and m i l l e r s i n New f o r k S t a t e . The t a l c c o n c e r n e d which is V ' h e a v ily contam inated with^aronhiboles and f r e e s ilic a was i n i t i a l l y reported to be a sso c ia te d w ith an in c r e a s e d m o r t a l i t y from m esoth eliom a and c o r ii p u lm o n a le . Later the same workers reported that men employed in th e mine a f t e r d u st l e v e l s had been red u ced , had death r a t e s from m alignant d is e a s e s th a t were s im ila r It- to th ose for white males in the U.S'.A. g e n e r a lly i3 A ls o in th e U . S . A . , F in e and h i s c o l l e a g u e s have r e p o r te d a h ig h e r p r e v a l e n c e o f p r o d u c t iv e cough and c h r o n ic o b s t r u c t i v e lu n g d i s e a s e among ru b b er w o r k e r s e x p o sed t o a n o n - f i b r o u s i n d u s t r i a l grad e t a l c -erfc- J&J-0098695 JNJ 000038321  -5 th8n among control workers. - From their data they calculated that 3 a safe exposure level would have been 0.24 rog/m mass respirable particulate talc OS a time weighted average. In Italy, Hubino and his colleagues compared the spectra of causes of death among t a l c m iner9, t a l c m i l l e r s and a g r i c u l t u r a l w orkers. The t a l c m iners were exposed t o d u sts c o n t a i n i n g 5% s i l i c a a t l e v e l s f a r in e x c e s s o f t h r e s h hold l i m i t v a lu e . S i g n i f i c a n t l y more of them than of th e c o n tr o ls died from r e s p ir a to r y d is e a s e , but death r a t e s from a l l forms of ca n cer , in c lu d in g lung c a n c e r ,- were s i g n i f i c a n t l y lower among th e m iners than among. the controls. Dy contrast, among the talc millers, exposed to dusts containing 0.05% silica, but no detectable asbeBtoa, at concentrations Of 20 million particles per cubic foot, there was no excess of deaths from pulmonary disease or cancer of any site compared w ith the c o n t r o l group. The d e f i c i t of l u n g c a n c e r among t h e t a l c m in e r s i s p l a u s i b l e i n s o f a r as a s im il a r d e f i c i t o f lu n g c a n c e r among c o a l /> miners seems to be r e a l . An o n -g o in g stu d y of over 5200 p e r so n s, nm inly women, a t a f a c t o r y in B r i t a i n where c o s m e t ic t a l c h a s b een made and p acked fo r over 50 y e a r s, has so fa r r e v e a le d no ev id en ce of /t h ea lth hazard , but follow -u p would need to continue for at le a s t a fu rth er decade before one could be confident of a negative r e s u lt . Other le s s inform ative ep id em iological s tu d ie s are reviewed by if H ild ick -S m ith J&J-0098696 JNJ 000038322 Most s t u d i e s in anim als s u f f e r th e d e f i c i e n c y thut the Quality of the talc used wee not specified. An exception <7 ia 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 tho respiratory tract or incidence Of n e o p l a s i a a t any s i t e . Another exception is the report n by Wagner and h i s c o l l e a g u e s who saw no m e s o t h e lio m a s in 48 rats a fter the intrap leural adm inistration of cosm etic t a l c , whereas 18 out of 48 r a ts s im ila r ly exposed to c h ry so tile asb estos developed such tumours. The same workers exposed r a t e t o Cosm etic t a l c by th e i n h a l a t i o n ro u te on f i v e days a week f o r up t o 1 y e a r . At the highest level of exposure - about three times that studied by Wehner and his colleagues - there was slightly more pulmonary fibrosis than in controls, but no meaningful excess of pulmonary neoplasms. A number of less .relevant animal studies, all of which give negative results for carcinogenicity, are reviewed by Hildick- Smith 6 . In summary, there are at present no grounds for believing that normal consumer exposure to cosmetic talc has in the past led cither 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 agreed to by major manufacturers will present a health hazard. . J&J-0098697 JNJ 000038323 REFERENCES * 1 . G r e e n b e r g , M. and Lloyd' D a v i e s , T. A. B r i t . J . X ndustr. Med., 3 1 . 91 1 9 7 4 . 2 . B lu e r o e l, G . , P i z a , F. and Z is c b k a - K o n o r s a , W. Wiener K lin . W pchschft., 7 4 . 12, 1962. 3. L avis, B.R., Whitehead, J .K ., G i l l , M.E., Lee, P .N ., B u t t e r w o r t h , A.D. and R oe, F . J . C . B r i t '. J . C a n c er, 3 1 , 4 6 9 1 9 7 5 4. Vi'agner, J . C . , B e r r y , G . , S k id m o re, J . W. arid T i m b r e l ! , V . f B r i t . J . C ancer, 2.9, 2 5 2 , 1 9 7 4 . 5. H enderson, W. J. , J o s l i n , C . A . F . , T u r n b u ll, A.C. and G r if f it h s , K., J. O bstet. Gynaec. Br. Cmwlth., 7 8 , 266, 1971* 6.. H i l d i c k - S m i t h , G. Y . , B r i t . J . I n d u s t. Med.. 5 5 , 2 1 7 , 1976. 7. T o ile t P reparation s F ed eration L td. S p e c if ic a t io n No. 12: C osm etic T a le; Issu ed 1977* 8 . C.T. F. A. S p e c i f i c a t i o n . T a lc , C o sm e tic , The C o sm etic, Toilet^pand F ragran ce A s s o c i a t i o n , I n c .. , I s s u e 1 0 --7 1976. 9.. T o ilet Preparations Federation Ltd. Cosmetic T ale, issued 1977- A n a l y t ic a l Method 77: 10. Hamer, L . H . , R o l l e , F . R. and S c h e l z , J . P . , Amer, T n d u st. Hyg. A sso c. J . , 3 7 . 2 9 6 , 1976. 11. K l e i n f e l d , M ., M e s s i t e , J . , Kooyman, 0 . and Z a k i, M.H., Arch. Environ. Hlth., 14. 663, 196? K l e i n f e l d , M. , M e s s it e ,' J . and Z a k i , M. H. , J. Qccup. Med., 1 6 . 345, 1974. i^. F in e , L. J . , P e t e r s , J.M., W> A .j "> A r c h iv e s o f E n v ir o n . H e a l t h , 3 1 . 195 ' , 1 9 7 6 . p(.i s L-~J~ > J&J-0098698 JNJ 000038324 R u b in o , G . , S c a n s e t t i , G . , P i o l a t t o , G. and Romano, C . , J . Occn. i . Med. , 1 8 , 1 8 6 , 1 9 7 6 . Goldman, K . P . , B r i t . J . I n d . Med.. 2 2 . 7 2 , 1 9 6 7 . N ew house, M.L., M i l l e r , B. F. and Moore, W.K.S., Unpublished con trib u tion to Seminar "Biology of T alc u s e d i n H e a lt h p r o d u c t s " , C a r d i f f , W a le s , May 1 9 7 6 . W.ehner, A.P., Zwickei, G.M., Cannon, V.C., Carlton, W.W, Fd. Cosmet, T o x ic o l., 1 ` , 121, 1977 Watson, C.R. and Wagner, J.C., Berry, G., Cooke, T. J. , Hi l l , n.j., and Skidmore, J.W., Animal Experiments with to lc in Proceedings of 4th International Symposium on Inhaled Particles and Vapours. Edinburgh, 1975. To- ba^piibiiahed. . la 'll . J&J-0098699