Document 15jBYOrM7pJGQ94VgebG7xKR5

lie Cosmetic, loiletry and Fragrance Association, Inc. w /_ -J: ,'u 1625 EYE STREET, N.W., WASHINGTON, D. C. 2000S 202/393-2070 James H. Merritt Presiocnt Norman F. Estrin, Pti.D. Vice Prcsicirnt-- Science December 26, 1973 AUu X , IS O , Hearing Clerk Food & Drug Administration Department of Health, Education and Welfare Room 6-86 5600 Fishers Lane Rockville, MD 20852 Re- Proposed Order Method for Asbestos in Talc Published . ' in the Federal Register (38 F.R., No. 188, pgs. 27076-270ol) ' September 28, 1973 Dear Sir: This letter and attachment is being submitted in response co^ tne 'proposal'published on September 28, 1973 (Federal Register, Tbl. S3, No. 188, pages 27076-27031) in which a method is proposed lor the determination of asbestos particles in food and drugs._ The comments are being submitted on behalf^of The Cosmetic, Toile m y ^ and Fragrance Association, Inc., a national association represen- manufacturers and packers of cosmetic products ^as well as i_h.~ manufacturers and vendors or cosmetic produce ingredients an-- supplies. Members of the Association manufacture approximately 3 of the cosmetic products distributed in the United States. _While the Association is not directly affected by the Federal Register Proposal cited above, one of its scientiric subcommittees^ m e CTFA Talc Subcommittee, has completed a critical review o^. coni cal micro secure memcc published in this proposal. m bener that this review is reveiant for your consideration of this propose .1, the report of the CTFA Talc Subcommittee, dated December 10, 1J/3. is attached as part of this submission. As a result of round robin testing of five different types of talc, by members of the CTFA'Talc Subcommittee, the subcommittee conduct that the proDosed method does not provide a reliable means ror the detection of asbestos in talc and that it results m o m PLAINTIFFS EXHIBIT CAM-188 ITA-LG 00212 false-positive and false-negative findings. The procedure is also tedious and may consume as much time as one-half day per sample. The subcommittee has also reviewed several alternative methods to detect chrysotile and tremolite in talc including modifications of the optical microscopic method. As a result of its review the subcommittee feels confident that a feasible method can be developed, and recommends a collciborative effort between FDA and industry to develop such a method. The questions concerning asbestos detection and the relationship of asbestos to human health are indeed complexones. At a confer ence last month, sponsored by the National Institute of Environ mental Health Sciences and the Environmental Protection Agency, three serious difficulties in determining the effects of asbestos on human health were presented: 1. "The term asbestos itself is misleading, for it encom passes a whole group of minerals that are distinct from each other in chemical composition, particle size, and probably biological effect. 2. Many of these particles are so small that, detection is extremely difficult and time consuming, placing restraints on the scope of research that can be reasonably undertaken. Perhaps the most serious difficulty in asbestos research, however, is the very long period between initial exposure and evidence of biological effects."^) Other points made at this Government sponsored meeting that merit consideration were: 1. Chrysotile fibers are too small to be detected by conven tional optical microscopy. 2. Amphibole asbestos fibers are larger. But they also require sublight microscopes for careful examination and cannot be positively identified without additional microchemical or selective area diffraction analysis. 3. A question yet to be answered is the effect of low-level exposure to asbestos on the general population. . 4. Dr. Ian Webster of the National Institute for Occupational Diseases in Johannesburg, Republic of South Africa, reported at the conference that very little ingested asbestos penetrates the walls of the stomach and colon and that almost all that does is of the smaller chrysotile type. Chemical & Engineering News, December 10, 1973, pages 18-19. *>r\ ITA-LG 00213 J " Similarly, studies with inhaled asbestos also show ^that the fiber is absorbed is predominately the chrysotile ' type. .. 5. Dr. William Eisenberg of'"the Food and Drug Jvdministration v;as quoted as stating that "at present, analysis by .polarised light microscopy is used to determine purity of food and drugs, even though this method probably misses many of the smaller.and more easily absorbed asbestos fibers that may be present in these materials." In light of the perplexing questions raised at this conreience,, the Association considers it premature for FDA to impose its proposed optical method and place a limit on asbestos in talc f-or food use. ipj-jQ CTFA urges deferment of promulgation of the proposal until. 1. Determination of the standard deviation of the proposed compliance test method. . 2. Evaluation of the validity or the assumption that a single milligram sample can be taken as statistically representa tive of any lot as well as the limit size of any lot so sampled. . 3. A re-evaluation of the economic cost and practicality of the proposed Compliance Test Methods. 4. An intensive search is undertaken for an alternate procedure * that is more reliable and more practical than the proposed test methods. `' The Cosmetic, Toiletry and Fragrance Association, Inc., stands ^e=.cy to assist the Food and Drug Administration in method development _ research as well as to provide assistance in other areas discussed above where as its scientiric expertise may be o^. value. Cordially, Norman F. Estrin, Ph.D. Vice President - Science N F E :mp ... Attachment cc: CTF7\ Talc Subcommittee _ CTFA Scientific Advisory Committee Original and seven copies filed with Hearing Clerk. Copies sent to: Commissioner h. Schmidt Dr. R. Schaffner Mr. S. Fine Dr. V. Wodicka .* Mr. 'P. Hutt w ITA-LG 00214 REPORT OF CTFA TALC SUBCOMMITTEE ON METHOD TO DETECT CHRYSOTILE AND tremolite in talc. .' . - . December 10, 1973 The Scientific Advisory Committee of the Cosmetic, Toiletry & Fragrance Association, 1625 Eye Street, N.W., Washington, D.C. 20006 at a meeting held on September 2, 1973, designated that a subcommittee be set up to study the optical microscopic method proposed by the Food and Drug Administration. This method was published in the Federal Register of September 28, 1973. The present membership of the CTFA Talc-Subcommittee is shown on an attached sheet. ' . At the first meeting of the Subcommittee, it was agreed to submit several samples of talc to members who volunteered to apply the FDA proposed optical microscopic method. The following talc samples were distributed without identification - except for randomly applied and ,non-duplicated code numbers: . Italian Talc Montana Talc Montana Talc Vermont Talc Alabama Talc No. Carolina Talc . Source I Source" II . In addition, a sample of Italian Talc spiked w/w- with 1% chrysotile and 0.15% tremolite was sent to each participant. The participants were aware that the sample was spiked, but did not know the percentage of spiking. - The attached table summarizes all reports submitted: Final Report ITA-LG 00215 -2 - Sample Spiked Italian Montana- I Alabama Vermont No.Carolina Montana- II No. of Fibers ' No. of Fibers With R.I. Greater With R.I. Less Than 1590 Than 1574 Status With Regard to Pro posed FDA Method Mrs. Lucy McCrone, McCrone Associates for Chesebrough 320 120 0 0 0 0 -0 16 0 0 0 0 0' 0 Passes Passes Passes Passes Passes Passes Passes Mr. Harold Stanley of Pfizer Italian Montana- I Montana- ILAlabama Vermont No. Carolina Spiked 100 -- 100 ~100 ~100 100 100 < 1000 >100 >100 >100 >100 >100 >100 >100 Fails Chrysotile Passes trenolite Fails Chrysotile Passes tremolite Fails Chrysotile Passes tremolite Fails Chrysotile Passes tremolite Fails Chrysotile Passes tremolite Fails Chrysotile Passes tremolite Fails Chrysotile Passes tremolite Mr. David Hamer of Johnson & Johnson Italian Montana- I Montana- II Alabama Vermont No. Carolina 0 1` 25 0 0 0 ' 0 0 0 0 0 0 Passes Passes Passes Passes Passes Passes Spiked Italian Dr. John A. Reffner (U. of Conn.) for Avon 632 12,930 220 1,114 Fails Chrysotile Passes Tremolite ,Pails Chrysotile Passes Tremolite ITA-LG 00216 -3 - Sample , Montana-^ Montana-71 Alabama Vermont No. Carolina No. of Fibers ' No. of Fibers With R.I. Greater With R.I. Less Than 1590 ' Than 1574 Status With Regard to Pro- posed FDA Method Dr. John A. Reffner (U. of Conn.) for Avon Cont'd 0 ' 13 26 41 14 ' 5,844 9,281 15,125 165 . 11,852 Fails chrysotile Passes tremolite Fails chrysotile Passes tremolite Fails chrysotile Passes tremolite Fails chrysotile Passes tremolite Fails chrysotilePasses tremolite Dr. Tryggve Baak of United Sierra Spiked Italian Montanayl Montana-77 Alabama Vermont .. No. Carolina 3,000 1,000 0 0 0 o 500 . 2,000 0 0 0 0 0 0 Fails Passes Passes Passes Passes Passes Passes Richard E. Stevens of Ernest F. Fullam, Inc. for Whittaker C&D Italian Montana-7 Montana-77 Alabama Vermont No. Carolina 8,250 18,000 29,250 21,825 3,225 20,850 1,350 450 5,200 6,075 675 6,000 Fails chrysotile & :remolite Fails chrysotile & tremolire Fails chrysotile & :remolite Fails chrysotile & <.remoIits Fails chrysotile & 'remolite Fails chrysotile & iremolite Spiked sample was not run. ITA-LG 00217 -4 - Samp le No. of Fibers With R.I. Greater Than 1590 No. of Fibers With R.I. Less Than 1574 . Status With Regard to Pro posed FDA- Method Mrs. Lucy McCrone f McCrone Associates for Kolmar Italian Montana-I Montana-II Alabama Vermont *No, Carolina Spiked Sample ' 53 0 0 0 0 0 488 0 0. 0 0 0 0 16 Passes Passes Passes Passes Passes Passes Passes *Sample noted to contain some fiber bundles which are rolled up talc plus some non--fibrous tremolite . The following participants examined their samples but were unable conscientiously to count particles with confidence, therefore, did not report numbers : Miss Marie Jones for Dr. G. Cohen - Bristol-Myers Products Research Labs. Mr. Salvatore DiBianca - The Mennen Company . Liberty Mutual Insurance Co., Research Center - for Kolmar Laboratories Mr. John Facq - The Colgate Palmolive Company, Research Center The table reveals strong inconsistency between results obtained by the different scientists applying the method to the same group of coded talc samples. This inconsistency is the result of problems encountered in the methodology. 1 refractive index of talc -- one of the two indices exhibite l by talc plates standing on edge -- varies in value between 1.539 and 1.55C)1. This in combination with item 2, below, miy easily result in the mis-classification of such plates a.! fibrous, less than 1.574" and therefore chrysotile. Dr. Refiner of the University of Connecticut, in his report to Avon, admits that this factor is paramount - "counts for chrysotile are high since (talc) edges will often be mistaken for fibrous particles". -2 . The immersion method for the determination of-relative refractive index becomes unreliable when applied to extremely small (ca. 1 Jim)par tides. This is due in part to the fact that particles around 1 > TM in width approach the limit of resolution of the human eye when both size and contrast are considered, especially -when applying the Becke line technique prescribed. This will ITA-LG 00218 -5 - 2* cause eye.fatigue and resulting errors. Thus, a fine talc shard or plate on edge may be easily mistaken for an asbestos fiber. This applies to both'the chrysotile and amphibole . portions of the test. 3. It is quite likely that chlorite - a mineral of varied compo sition -commonly found in pharmaceutical grade talc - would be incorrectly Identified as tremolite. Refractive indices ' for chlorite vary in the range 1.57-1.66^. 4. The examination of a sample of one milligram dispersed on a single microscope slide presents the investigator with a * preparation which is too dense for a petrographic study. 5. The method is laborious and time consuming. Dr. Reffner quotes an analysis time of about five hours per sample and at JOHNSON & JOHNSON the investigator (D. H. Hamer) estimated at least two or three hours. 6. Dr. Walter C. MeCrone in an earlier letter to the FDA suggested that there were relatively few scientists in the country who could use the method effectively. Scientists at Bristol-Myers, The Mennen Company, Liberty Mutual and Colgate-Palmolive had great difficulty in following the method to conclusion. 7. The proposed FDA method implies that all fibrous particles in talc having optical properties similar to those of asbestos minerals are in fact asbestos. This is probably an unwarranted assumption. REFERENCES: 1. Deer, W.A., Howie, R.A., and Zussman, J . , Rock-Forming Minerals, Vol. 3, p. 121 (1962). 2. ibid, p. 131. ***************** We have concluded that the method published in the Federal Register does not provide a truly reliable means for the detection of asbestos in talc. It results in both false-positive and false-negative findings. It is also tedious and may consume as much as one half day per sample. The subcommittee urges that the Food and Drug Administration defer finalizing the proposed optical microscopic method and proceed into a Phase II program which would combine FDA and Industry in a strong effort to develop a truly reliable method for measuring chrysotile content in taile. We are confident that the detection and estimation of fibrous tremolite can also be done, if necessary, as a fringe benefit, at the same time. . ITA-LG 00219 -6 - . We estimate that a satisfactory method will take at least six months to a year to develop. We suggest a close liaison between FDA and industry in this all-out effort with updating reviews to take place as frequently as necessary. ' "' ' ` Review of Alternate Methods The CTFA Talc Subcommittee has reviewed several methods to detect chrysotile and tremolite in talc, including modifications of the optical microscopic method. These are listed with comments. ' 1 . Optical Microscopic Method - may be used with some modification. Possibly better selection of R.I. liquids and reduction of sample size per slide. 2. X-ray Step Scanning - A good method for detecting tremolite if we could accept about 0.2% as the threshold of detection. It does not distinguish fibrous from non-fibrous tremolite. The simultaneous 'detection of chlorite makes method impractical for chrysotile. X-Ray Step Scanning + Optical Microscopy - Acceptable as in #2 above but the optical method continues to present the dilemma in reliable identification of chrysotile. However, this does not rule out a major revision of the optical method to do the chrysotile identification and counting. X-Ray Scanning - The problem of chlorite interference in the detection of chrysotile is present in all x-ray procedures thus far available. It is reliable for the detection of 1% tremolite (both fibrous and non-fibrous). Differential Thermal Analysis - This procedure is capable of detecting chrysotile at the 1% level, however, it will not detect tremolite. Scanning ElectronMicrosconv - This procedure is not capable of identi fying asbestos. Even with energy dispersive analysis, completely satisfactory identification is not possible. 7 Transmission Electron Microscopy + Electron Diffraction - This appears to offer the best, most reliable method and is probably capable of detecting chrysotile and tremolite (fibrous), both at a level of 0.1%. It is estimated that an installation would cost about $130M +, and is obviously prohibitive for the small manufacturer who uses talc. The amount of talc sample examined by this procedure is miniscule. * ITA-LG 00220 *' ... -7 - .The CTFA Talc Subcommittee has completed its review of the Optical Microscopic Method for the Estimation of Chrysotile and Fibrous Tremolite in Talc, which appeared in the Federal Register, vol. 38 (No. .188),(p. 27076, September 28, 1973). It recommends postponement of the finalization of the proposed regulation oh talc. In addition, a collaborative effort between FDA & industry to resolve a satisfactory method of estimating chrysotile and tremolite in talc, is recommended, with periodic-liaison reviews to monitor the project status. A task force of industry experts has been designated to pursue alternate methods. We invite FDA to participate in collaboration with the task force. '''? a ? ./. .. George'W. Sandland Chairman CTFA Talc Subcommittee GWS:dd ITA-LG 00221