Document 6BxO5mB2jKwXvxLMRZMbggY86

SUMMARY MINUTES OF THE OTC PANEL ON ANTIPERSPIRANT DRUG PRODUCTS Twelfth Meeting Ju ly 9 and 10, .1975 Parklawn Building 5600 Fishers Lane, R o c k v ille , MD 20852 PANEL MEMBERS E. W illiam Rosenberg, M.D..Chairman Zenona M ally, M.D. Charles Evans, M.D., Ph.D. Jane Rosenzweig, M.D. Robert Scheuplein, Ph.D. LIAISON MEMBERS Consumer Ms. Marsha Gardner Industry Robert Giovacchini, Ph.D. FDA STAFF MEMBERS Mary K. Bruch, Executive Secretary - Division of A n ti-In fe ctiv e Drug Products Lee Geismar, Panel Adm inistrator - OTC D ivision Joseph Hussion, Drug Information Analyst - OTC D ivisio n Robert Pinco, D irector - OTC Division Dr. Albert M ille r , Consultant to FDA CTFA REPRESENTATIVES G. Hi 1dick-Sm ith, M.D. - D irector, Medical A ffa ir s , Johnson & Johnson F. Pooley, Ph.D. - Department of Mineral Exploitatio n, U niversity College C a rd iff, Wales, U.K. F. R. R o lle , Ph.D. - A ssistan t Manager of A nalytical Research, Johnson & Johnson G. Lord, D.V.M., Ph.D. - D irector, Johnson & Johnson Research Foundation A. Wenner, D.M.D. - Biology Department B a tte lle P a c ific Northwest Laboratories R. Wulf, Ph.D. - A ssistan t Research D irector, Carter Products Research, Carter Wallace, In c. W. E. Smith, M.D. - D irecto r, Health Research In s titu te , Fairleig h Dickinson University j*.: .V.V .V -V /.V .'. J- V .V .V ..V r.v .v .v .v .* .* : l: ::::::: c ::::: t: h v.V .V .V .7 . \V7.*- > '/ Decisions reported herein are. provisional in nature and may be modified or revised in subsequent meetings of the Panel or in th e ir fin a l complete report to the Commissioner. Whenever there is a lack of unanimity on any given point, the vote w ill be given. Regulations do not permit voting by the Liaison Members, Consultants, or FDA S ta ff Members. Adopted_ y /j 7 l 2 L . w ho Chairman / E. Wil 1iany^osenberg, M. D. rr.Trrr.Trr r.r.r.'.v.:*.:! f.v .v .w V .v .' ir .v .r .v r .v : CZXZZUSUl r.v .v .'.v .u .'.: W rr.v .v rrr: ' f-W .V .W .V . * > -.V .V .V .'.V, ! r.`.'.v .v .v ,v . p .v :.v :: ' rrrr.v.w r: r-I'-W .iV .IV SUMMARY MINUTES The OTC Antiperspirant Panel met in the Parklawn Building on Ju ly 9 and 10, 1975. Drs. Shefter and Clayton were unable to attend the meeting. Open Session: An extensive open session was held to discuss the id e n tific a tio n and to x ic ity of ta lc . Talc and starch are used in the formulation of aerosolized an tip ersp iran ts. The Cosmetic T o ile t r ie s , Frangrance Association made an industry presentation. Dr. A lbert M ille r of Mount Sinai Hospital was present as an expert invited-by the Panel to discuss the presentation made by the industry group and to discuss his own work as part of a group at Mount Sinai doing research in Environmental Health and S afety. CTFA Presentation ! ' '1 *_ Dr. Gavin Hildick-Smith of Johnson and Johnson served as, coordinator for the presentation and introduced the speakers. He told the Panel that the subject is complex and hoped that the presentation would better help them to understand the d istin ctio n s in the types of ta lc used in cosmetic products. -2- Dr. Pooley's Presentation ' '' Dr. Pooley was present as an expert consultant to the CTFA group. He is from the Deptartment of Mineral E xp lo ita tio n 8 U n iversity College, C a rd iff, Wales, U.K. He spoke on the mineralogy of t a lc . He lis te d some of the minerals found in t a lc , exp ecially the asbestos m inerals, which are the point of concern for the Panel. There are two groups of asbestos m inerals: 1) The serpentine group and 2) The amphibole group. The serpentine group contain a mineral calle d ch ryso tile and the amphibole group contains minerals such as c ro c id o lite , amosite, antho phyllite, tre m o lite , and a c tin o lite . Talc powder refers to an in d u s tria lly used material which contains from 40 to 95 percent by weight of t a lc m ineral. The ta lc mineral i t s e l f is sheet s ilic a t e . _i In pure ta lc there is 31.7 percent magnesium oxide, 63.5 per- cent s ilic o n dioxide and 4.8 percent water, by weight. , Dr. Pooley described the formation of ta lc and pointed out that often there are intrusions of other minerals into the ta lc s it e . The minerological composition of t a lc , including the mineral fibrous (asbestiform ) and non-fibrous (non- j :::r. r t.v .v .v .v / .v . Iv .v .v .v r/ .v . i.V .'.V .V .V ..'. v.w w w w w f.'.V .'.V .V .'.*. -3- asb estifo rm ), depends on the geological formations present at the source of the t a lc . Cosmetic grade ta lc (p laty ta lc ) normally contains 90 percent ta lc with the contaminates being carbonate'and c h lo rite minerals. Dr. M ille r questioned Dr. Pooley about the asbestiform content of the cosmetic ta lc that he had analyzed. Dr. Pooley said that he had found no ch ryso tile in about 40 samples from d iffe re n t sources. There was detectible amounts of trem olite in a few samples. . Dr. M ille r commented that he believed an alysis on the fin ish ed product rather than th ta lc at the source would provide more information about possible r is k to the con sumer. : Some questions concerning the adequacy of types of analysis of ta lc components were deferred u n til a fte r Dr. R o lle's presentation. t ; Dr. R o lle's Presentation Dr. Rolle of Johnson and Johnson re ite rated some points about content o f- ta lc to distinguish in d u stria l and cosmetic r.v .- .v .v .- v . f- .T r.rr.v r.T p .'/ .r .v .;* : L v .v .v .v .v . ::::::::::: v .v .v .v .v . -4- t a lc . Because of allegations that ta lc contained asbestos8 a CTFA task force was formed on the methodology for identifying asbestos in t a lc . The committee decided that the method fo r determining fibrous and non-fibrous content must be sp ecified , have definable detection lim its and must be reproducible with c r it e r ia fo r pass or fa il., fo r a sample. r A c r it ic a l element is the d e fin itio n of a fib e r. Dr. Rolle read the d e fin itio n of the Department of Labor, Occupational Safety and Health Administration as: "must appear to be fibrous rather than c ry sta ls or s liv e r s , the maximum diameter of a fib e r to be counted is 3 microns,, the minimum length of a fib e r to be counted is 30 microns, the length to width ra tio is 5 or more to one." A fter examining procedures such as scanning electron micro scopy, in fra-re d and optical microscopy, the Task force selected x-ray d iffractio n with a detection lim it of 0.5 percent. I f amphibole p a rticle s are present, the fibrous... m aterial is examined by optical microscopy and dispersion s ta in in g . I f i t is detected as a fibrous amphibole, the talc fa ils . , '.I'.'.r .'.'.i- :::::::::::: .V .V .V .V .V iv .v .v .v .v ::::r -5 The Task force selected d iffe re n tia l thermal analysis (DTA) as the procedure for id en tifyin g c h ry s o tile . rv .v /.-.-.v .v .v r.'.v .v .r .v .* / . Dr. M ille r commented on Dr. R o lle 's t a lk . He said that the medical profession and the consumer are interested not only in c h ry so lite but in any amphibole fra c tio n . He f e lt that x-ray d iffra c tio n was a less se n sitive method than scanning electron microscopy. Dr. M ille r quoted a standard 'for asbestos in in d u strial sources from the Western Health In d u stria l Conference. This source stated that no level of asbestos minerals should be developed as a standard when considering,.carcinogenic, e ffe c ts . I f th is goal v/ere accepted, the goal would be no asbestiform p a rtic le s . crx v.so t , , L Dr. R o lle in commenting on the mineral^contamination of ta lc said that i t is incorporated as an integral p art, deep in the la t t ic e structure of the ta lc and in that position is in e rt and does not come out. tv .v .v .v .v .'r == Iv .v .v ." " : ::::::::: Presentation by Dr. Hildick-Sm ith * . *' The long and widespread use of ta lc in cosmetic products was reviewed. In the publications concerning ta lc there is \ frequently no description of the type of ta lc used and i t is therefore d if f ic u lt to assess the a c t iv it y of cosmetic grade t a lc . Published a rtic le s re late to three areas: 1. In d u strial health. Reports of miners health a fte r prolonged exposure to high le ve ls of minerals often containing asbestos. . t::.-:- , if, .................................. 2. Accidental su ffo catio n . Pulmonary in s u lt occuring often as a re su lt of s p illin g large amounts of powder on the the face of an in fan t or c h ild . 3. Misuse or excessive exposure. Reports of individ uals who have overused products. Talc has been shown not to be an allerg en . In in v itro y tissu e culture stu d ie s, various mineral dusts produced a fib ro b la s tic response while cosmetic ta lc produced no change. In a study of pulmonary macrophage function, no attenuation in function was noted with cosmetic ta lc . Presentation by Dr. Wehner Dr. Wehner is with the B ate lle P a c ific Northwest Laboratories. He described an animal study in hamsters with ta lc in which the exposed animals were allowed to liv e out rr.* :.* rrrrr.'r. IV--*.V.VV.V -7- th eir l i f e span. Hamsters were exposed for 30 days to simulate the ta lc exposure of human infants since th is period would correspond to the in fan t l i f e of the hamster Another group was exposed fo r 300 days which was considered equivalent in the hamster to the l i f e span of a woman through her child-bearing years.. The hamster was chosen because i t was shown to be an appropriate animal for testing potential carcinogens. No adverse e ffe cts from the ta lc were found in the treated animals. Both te s t and control animals showed'these random pathological e ffe cts on necropsy. Dr. Wehner was. asked about concentration procedures in order to increase the detection lim it of asbesti form p a rtic le s . - i Presentation by Dr. Wulf Dr. Wulf of Carter Products described inhalation tests with a product made by them containing t a lc , Light Powder Arrid A n tip ersp iran t.. ' The product contains 0.75 percentIt a lia n t a lc . A 90-day subacute aerosol inhalation te s t, in ra ts was performed in which animals were exposed to a 30-second burst follow by 15-minute exposure to the resu ltin g lv .v . :* .: :: : t.v .v .v .v .v h: j.- jr r tv.v.v.v-- \ -8I aerosol fo r 5 day/week f o r '13 weeks (130 exposures). No adverse e ffe cts were seen in control or te st animals. A second s im ila r test was run in monkeys with the exposure concentration estimated as 10 times higher than in the rat study. Lung function studies were performed on the monkeys. No adverse effects attrib u ta b le to the product were noted. Dr. M ille r noted that from the h isto ry of delay of the onset of adverse pulmonary function e ffe cts in in d u strial workers i t would be u n like ly to see function changes in monkeys in 90 days,.. ' Presentation by Dr. Smith i Dr. A. E. Smith of Health Research In s titu te of Farleigh Dickinson U niversity described feeding studies in hamsters. He gave hamsters asbestiform minerals in th e ir feed. Varying incidence of tumors' (mesotheliomas) were observed... in animals at 25 and 10 mg with the four major forms of asbestiform m inerals. D ifferen t minerals showed effects at varying dose le v e ls . Dr. Smith found no tumors in animals dosed with trem olite t a lc . The ta lc used in the L- . .- - .---... r.-.v -9- te st was in d u strial t a lc . When the ch ryso tile was reduced to submicroscopic p a rticle s and tested in the hamsters, no turmors Were found. . Presentation by Dr. Hi!dick-Sm ith Dr. Hi!dick-Sm ith described a study designed to examine ta lc mine workers to determine i f th e ir cause of death is d iffe re n t from a sim ila r control population. Deaths fo r a ll types of carcinogenesis, overall deaths and resp irato ry diseases were compared. Respiratory disease deaths were increased among, miners. This study was performed by Professor Rubino, of It a ly , and presented at the meeting of * the American Occupational Medical Association, Turin I t a ly , Oct. 7, 1974. Dr. M ille r pointed out some problems in epidemiologic studies when th is type of worker population is selected. He f e l t that the death' c e r t ific a t e might not be a re lia b le .source of information on the cause of death because they would be a poor source of such information in th is setting and would, in the time period studied, be u n re liab le . i Dr. Hildick-Sm ith summarized the conclusions which can be drawn from the information presented by the CTFA Group. -10- Presentation by Dr. M ille r Dr. M ille r of Mount Sinai Hospital discussed his own work . and his view of the e a r lie r presentations. He described his in te re st in' the content of ta lc and the epidemiology of eny disease caused by i t . Dr. M ille r questioned the d istin ctio n between cosmetic and in d u strial ta lc as i t is now made. He thought that perhaps this did not necessarily apply to the cosmetic ta lc s in wide use in the past as fa r as analysis of asbestos content. Dr. M ille r quoted work by Dr-. Arthur Langer of Mount Sinai Hospital in which he analyzed 50. commerical cosmetic powders by various methods including electron microscopy. He did find several powders i with up to 30 percent quartz. One powder showed 30 percent anthophyllite and trem o lite, which are asbestiform fib e rs . He emphasized that he thought i t was important to analyze the product from the sh e lf rather than at the source in the mine. Dr. M ille r quoted a study by Schepers and Durkan in the Archives of In d u strial Health (12:182-197, 1955), in which inflamatorv response was found in animals in su fflate d with true t a lc . He described another study by K lein feld et a l . (Environmental Research 6:132-143} at the New York Department of Health in which changes in pulmonary function w v .v . v .: r .v .v .v .v ;; .v .v /.v .v . :::::::::: -n- were seen in workers exposed to both fibrous and granular t a lc . The exact means of d iffe re n tia tio n of the ta lc was not d etailed . Dr. M ille r referred to several cases where pneumoconiosis or other lung effects were reported in patients who had excessive exposures to ta lc in work situ atio n s or with overuse. W. L The d if f ic u lt ie s in id en tifyin g fibrous p a rtic le s by some of the methods used in the references cited by Dr. M ille r were discussed following Dr. M ille r's summary. Closed Sessions,:, ^ * \ Discussion of T o xicity of Talc in Aerosolized Antiperspirants The Panel reviewed the presentations by CTFA and Dr. M ille r. The Panel urged that fu rth er work be undertaken to set lim its fo r asbestiform fib e rs and to reduce the lim it of detection to as low as'p o ssib le from the presently accepted 0.5 percent. The Panel accepted that there is v ir t u a lly no r is k from asbestos in aerosolized ta lc in the amounts found in an tip ersp iran ts i f the material is determined to k-W .'.-.V/.V. .V .'.V .V .V .'t ..v .v .v .v . / .`.V .'.'.'.V \ - 12- 'jl \ ' / be cosmetic ta lc free o f' asbestiform fib e rs , determined by the CTFA procedure. This procedure should pertain ' u n til more sen sitive a n a lytica l techniques are a vaila b le . They concluded that the use of ta lc in antiperspirants constituted only a small portion of the potential problem with ta lc in the environment in view, of the much larger experience accompanying the use of baby powders. They f e lt th is exposure to ta lc would not constitute a hazard. The Panel did not consider the safe ty of ta lc in products other than an tip ersp iran ts. E ffic a c y Pi scussion:^ , The Panel made a general plan of work s t i l l remaining to be done. l One large portion of the review s t i l l remaining is the review of effectiveness testing procedures. The necessity fo r te s ts , type of te sts and the procedures fo r in terp retin g them were discussed. Some Panel members thought that most te st re s u lts showed a reduction of- perspiration f e ll in a range between 20 i I :::;:::::: -13- and 40 percent based on the OTC submissions. The typeof te s t to be run and the subsequent use of the re su lts in making comparative labeling claims were discussed. The d if f ic u lt ie s in testing the effectiveness of active ingredients when they are influenced by formulation in products was discussed. Mr. Pinco of the OTC s t a f f discussed the scope of the regulations which apply to review of the ingredients rather than products. The Panel discussed the problem of attempting, to determine the e ffic a c y of antiperspirants without testing them in product form. No fin a l decisions^, were made but general ideas of Panel members concerning effectiveness were expressed and reviewed. The differences in the re su lts obtained in hot room testing and in in-use testing and the possible ways of interpreting them were outlined. The-use of a highly selected population in one case was contrasted to the use situ atio n in the wideranging population who use the product d a ily . L tw .v .v .v iv.w .v.v.v. u r .'.'U v .'.v h :: : : : : : : : : t: :::::::::::: i: jlV .-.V .'.'.'.'.V {.v .v .v .v .v . '//.V .V .'.V rrir:::r.7rTM v.r4:r,:7;r.v.;;r.v -14- The p o s s ib ility of developing a te st with sp e cificatio n s and c r it e r ia fo r in terp retatio n which would determine whether a sp e cific product met a minimum effectiveness level was ra ised . The Panel agreed to request through th e ir industry lia iso n member that industry present th e ir various procedures fo r testing and analysis of the te st re su lts at the next Panel meeting. Some of the pertinent d e ta ils to be discussed are the degree of reduction in hot room tests and its re la tio n to e ffectiven ess, type of analysis of re s u lts , number of su b jects, co n tro ls, use-tests, and label claim s. The idea that antiperspirants may not be e ffe c tiv e at a ll w ill be raised . \ The August meeting to discuss effectiveness is scheduled fo r August 14 - 15, 1975 and a meeting is scheduled for September 18 - 19, 1975 at the Parklawn Building. Prepared by: Executive S e c re te