Document 0qQwk9oNm0p9vKm15R1NnvNJJ

DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE PUBLIC HEALTH SERVICE FOO D AND DRUG ADMINISTRATION W A S H IN G T O N , .C . ZQ2D4 /_ //- ( / ^ T i 7} f i , f s t f r A- {/& / O i &u f- , a l f Fox your in fo rm atio n . JAN 2 6 1979 'M iratila Clark & DANIELS n A . W enninger Deputy D ire cto r D iv is io n o f Cosm etics Technology Food and Drug A d m in istra tio n ,200 "C" S t r e e t , S .W . W ashington C . 20204 (2021 245 1061 PLA NT FF 5 EXHIBIT W C D -4 0 8 Goodhue WCD 000778 DEPARTMENT OF HEALTH. EDUCATION. AND WELFARE- PUBLIC H EA LTH SERVICE , FOOD AND D R U G ADMINISTRATION j R O C K V I L L E . M A R Y L A N D 20857 | J : > 1373 w, 1 Sidney M. Wolfe, M.D,, Mr. Benjamin Gordon Public Citizen Health Research Group 2000 P S tr e e t, N.W. Washington, D .C. 20036 Dear Dr. Wolfe and Mr. Gordon: Your le t te r o f August 4 , 1978, raised the question of ta lc carcino genesis based on two le tte r s submitted to the New England Journal of Med icin e e a r lie r th is year. In p a rticu la r, Dr. Marshall Deutsch stated th at t a lc is clo se ly related to the carcinogen asbestos and is lik e ly ' to contain microscopic asbestos p a r tic le s . Both ta lc and asbestos have been o f concern to the Food and Drug Administration fo r several years,- and we welcome th is opportunity to discuss our continuous work in th is area with you. We w ill preface our remarks, however, with some back ground m aterial {Sections 1-2). - 1. References Cited . The references cited in your le tte r are useful only because they ra ise an issue that deserves consideration on it s own m erits. The references themselves, however, are merely personal le tte rs to the e d ito r; th e ir claims are neither s c ie n t ific a lly controlled studies' by the authors nor reviewed by peers. Indeed the le tte r of Moorehead and Del merely refers to the one by Deutsch, who in turn quotes from a paragraph in C lin ic a l Chemistry 22(7):1141. 1976, about an oral presentation to be given by K. G r iffit h s . This . paragraph speaks only about "electron microscopic microanalysis" fo r id e n tifica tio n in tissu e o f "contaminating p article s such as asbestos or t a l c . . . Dr. Deutsch's assertion that asbestos p articles found on su rgi c a lly removed ovaries could have migrated from ta lc used to dust condoms is unsupported speculation. He further asserts that . Japanese men have more stomach cancer than men in other countries because they_ingest ric e dusted "with a mixture of ta lc and g lu c o s e .11 He gives no reference, but presumably has in mind "TalcTreated Rice and Japanese Stomach Cancer," by R.R, Merliss Science 173:1141-42, 1971. The fa c t s , however, are that most Japanese eat unpolished r ic e ; only the afflu en t can afford JAN I 8 I9T9 Goodhue WCD 000779 Page 2 - Sidney M. Wolfe, M.D. polished rice coated with glucose and t a lc . Furthermore, persons o f Japanese ancestry in Hawaii and C alifo rn ia, who do eat polished, coated r ic e , have a lower incidence of stomach cancer than the native Japanese! Apparently, the native Japanese are affected by many other environmental factors that could cause stomach cancer (see Haenszel, W., M. Kurihara, M. Segi andR .K .C . Lee, "Stomach Cancer among Japanese in Hawaii," Journal, of ( the National Cancer In stitu te 49(4)969-988, October 1972). F in a lly , Moorehead and Oei allege that FDA regulations discourage the replacement of talc in older drugs. The extent of testing to assure the adequacy of the reformulated products depends upon the drug i t s e l f . Currently, the replacement of ta lc with an accept able excipient would not change its drug status; that i s , new drug applications would not be required fo r "old1; drugs. Although new .drugs would require, a supplemental application, the firm may s t i l l market it s currently approved formulation while it s application is pending. The FDA-sanctioned hardships alleged by Moorehead and Oei appear to be without foundation. 2. Asbestos versus Talc - Talc is a naturally occurring hydrous magnesium s ilic a t e sim ilar in chemical composition to various asbestos m inerals. However, unlike the fibrous forms o f asbestos, ta lc normally exists as tabular or platy forms (attachment A). Indeed most asbestiform minerals also exist in non-fibrous forms. (See Dr. AmpianJ s a r tic le in attachment B.) Thus ta lc and asbestos are not sim ilar in morphology. As you know, such experts as Mearl F. Stanton (NIH/National Cancer In stitu te) contend, on the basis o f several stu d ies, that i t is not the chemical nature of asbestos as much as it s physical configuration--long thin fib ers--which make i t carcin ogenic (attachment C). There is to date no conclusive evidence that pure ta lc 1s carcinogenic in man or animals (attachment D). The FDA Asbestos Work Group and the OTC Panel on Antiperspirant Drug Products have reviewed the voluminous lite ra tu re on t a lc and have independently determined that the evidence.implicates ashes,, . tos contamination of ta lc as the offending exposure in " t a lc 11 carcinogenesis. Industry awareness of our concern has led to improvement in the mining and processing of ta lc to minimize asbestos contamination. In 1973, the FDA published a proposed rule to prohibit the use of ta lc contaminated at the 0.1 percent level with asbestos in foods and drugs (38 FR 27076, September 28, 1973, attachment E). Imple mentation of th is rule has been necessarily delayed until an appropriately.sensitive method for regulatory purposes could be Goodhue WCD 000780 Page 3 - Sidney M. Wolfe, M.D. developed (40 FR 11865, March 14, 1975, attachment F ), In coop eration with s c ie n tists from industry, our sc ie n tists have been making progress in the development o f such regulatory methods (attachment B). Meanwhile, the FDA Bureau of Foods has carried out several x-ray powder d iffra c tio n surveys of the asbestos contamination of cos metic t a lc (talcum powders). They found that cosmetic grades of i ta lc are usually fre e of asbestiform p a r tic le s . For example, in a 1977 investigation of 46 ta lc samples, the FDA found only three to contain asbestos (trem olite or anthophyllite; see attachment E) and even then the level was only 0.1 percent or le s s . One firm , Johnson & Johnson, has also done extensive testing fo r asbestiform p a rticle s in cosmetic-grade ta lc ; a ll results to date have been negative. Status of Current Studies on the Health Effects of Asbestos and Talc Even in the case o f asbestos-contamination, one must distinguish between the lik e ly routes of exposure: in halation , in je ctio n , and ingestion. In man, inhalation exposure to asbestos, especially when combined with cigarette smoking, has produced lung cancers. This has been well documented by S e lik o ff, by Hatirnond, and others in epidemiological studies of industrial workers (see references in attachment E). We are also aware of animal studies of asbestos inhalation which report lung tumors (attachment G). Government agencies are sponsoring to xicolo gical studies in ani mals on the e ffe c ts of ingested and injected asbestos. Two of th ese, supported by the Environmental Protection Agency and the National In s titu te of Environmental Health Sciences, involve the ingestion of various kinds of asbestos p articles by both hamsters and rats (attachment H). These studies were started only recently and FDA w ill follow their outcome c lo se ly . Two FDA in je ctio n studies using six'dose levels o f small chrysot i l e fib ers administered intravenously in both rats and mice (e sse n tia lly life tim e studies) have gone to necropsy. An excess o f lung tumors in the high dose mice, but not in ra ts , as compared to controls is suggested from preliminary, unanalyzed reports of gross necropsy fin d in g s. Histopathology and s ta tis t ic a l analyses w ill require about seven months to complete. Already, however, the use of asbestos in f ilt e r s used in the manufacture of paren te ra l drugs is restricted by FDA regulation (attachments E and F). Goodhue WCD 000781 Page 4 - Sidney M Wolfe M.D. F in a lly , there are two animal inhalation studies on ta lc i t s e l f . The completed study was negative fo r carcinogenesis (attachment I ) . The ongoing study, contracted by FDA with Lovelace Founda tio n , Albuquerque, New Mexico, and in itia te d in 1975, has shown no p ositive re s u lt thus fa r . There are, to our knowledge, no cur rent, d irect studies of ta lc ingestion or intravenous in je ctio n , since the former has not yet been shown to be a hazard--even for asbestos i t s e l f --and asbestos contamination of the la tte r is already unacceptable. In suttmary, we share your interest in the safety of ta lc m foods, drugs and cosmetics. The FDA is continuing it s study of ta lc through the sponsorship o f contracts for methods development and for animal studies; we also attempt to communicate with external s c ie n tific groups perform ing sim ilar animal or epidemiologic studies At present, we believe that i f ta lc poses any risks in the products under our control, i t is related to contamination by asbestos fib e r s . However, the FDA is pre pared to take whatever prudent additional action is indicated to protect the public h ealth , i f and when results of d e fin itiv e tests show that the kinds of ta lc in foods, drugs, or cosmetics may represent a carcinogenic hazard FDA and other governmental agencies are well aware of the dangers o f asbestos and are actively seeking the necessary information to establish enforceable lim its on these mineral p articles in products under our co n tro l. We hope th at these comments f u lly respond to your inquiry about our current e ffo r ts m th is area. I f you need further information, please contact Dr. Armand Casla, chairman of the FDA Asbestos Work Group. You may reach him by telephoning 301-443^6714, or by writing him at the Bureau o f Drugs, Division of A n ti-In fectiv e Drug Products (HFD-140). Sincerely yours, Enclosures (9) Donald Kennedy Commissioner of Food and Drugs Goodhue WCD 000782 Goodhue WCD 000783 Goodhue WCD 000784