Document 2JLNvBkbm7r51qk23w9bw5yvg

c f THE COSMETIC, TOILETRY, AND FRAGRANCE ASSOCIATION April 24, 2001 Dr. C. W. Jameson National Toxicology Program Report on Carcinogens MD EC-14 P.O. Box 12233 Research Triangle Park, NC 27709 E. E DWARD K A V A N A U G H PRESIDENT RE: Call for Public Comments on 8 Nominations, Proposed for Listing in or Delisting From the Report on Carcinogens, Tenth Edition (66 Federal Register 13334): Talc Not Containing Asbestiform Fibers Dear Dr. Jameson, The Cosmetic, Toiletry, and Fragrance Association1(CTFA) appreciates the opportunity to provide comments on the above referenced topic. Talc not containing asbestiform fibers is used within the personal care products industry, and thus, the review for possible listing in the 10th Report on Carcinogens is of significant interest to CTFA members. The definition o ftalc, which was a point o f considerable debate at the Board o f Scientific Counselors (BSC) meeting in December, is addressed in these comments. Because a valid conclusion regarding carcinogenesis cannot be reached without a clear understanding o f the substance being evaluated, a clarification of the definition o f talc is provided herein. Also included in these comments is a very brief summary o f the substantial comments submitted to NTP prior to the BSC meeting. The previous comments are included in this comment by reference. NTP cited both ovarian cancer epidemiology studies and an NTP rat chronic inhalation study as the basis for proposing the listing o f "talc not containing asbestiform fibers" in its 10th Report on Carcinogens. Detailed comments addressing these issues were submitted prior to the December meeting and again, are included by reference. The comments and the discussion at the meeting, as recorded in the meeting transcript, make it clear that much consideration was given to both o f these *CTFA is the U.S. national trade association representing the personal care products industry. CTFA is comprised o f about 300 active members that produce the vast majority o f the cosmetics distributed in the U.S. and many over-the-counter drugs designed for dermal application. The association also has about 300 associate members that provide raw ingredients and supplies and services to the industry. Many o f CTFA's members are international companies that do business in foreign countries as well. 1101 17TH ST., N.W., SUITE 300 WASHINGTON, D.C. 20036-4702 202.331.1 770 fax 202.331.1 969 PLAINTIFFS EXHIBIT http://www.clfa.org SECURING THE INDUSTRY'S FUTURE SINCE 1894 CAM-215 Page 2 Dr. C.W. Jameson April 24, 2001 issues before the BSC voted 7-3 in favor o f not listing "talc not containing asbestiform fibers" in the 10thReport on Carcinogens. This is in contrast to a statement in the Federal Register notice that the ovarian cancer studies were not considered. At the BSC meeting, the motion which passed bv a vote of 7-3 was "not to list talc not containing asbestiform fibers." "Talc" and "asbestiform" definitions are presented here. A clear understanding o f the definition o f the material being evaluated is fundamental to reaching a valid conclusion as to its carcinogenicity. Technical comments by experts in the field o f mineralogy were submitted to NTP for the purpose o f clarifying the definitions of talc and asbestiform fibers.2 Consistent with those submissions, the following definitions o f "talc" and "asbestiform", as those mineralogical terms are defined and understood by professionals in the geological sciences, are presented: Talc (CAS Registry Number: 14807-96-61 Talc [Mg3Si40jo(OH)2] is a hydrous magnesium silicate consisting theoretically o f 31.7% MgO, 63.5% S i02 and 4.8% H 2O. Pure talc is a translucent mineral with a Mohs hardness o f 1 and is considered the softest and least abrasive o f minerals. Commercial high quality grades o f talc offer fine particle sizes in the range o f 1-20 yum, a very hydrophobic surface, organophilic in nature, tremendous slip as a result o f its lamellar (platy) crystal formation, heat stability up to 900C, are inert in most chemical reagents and are typically utilized in ceramic, paper, plastic, paint, roofing, rubber, cosmetic and pharmaceutical applications.3 Asbestiform The term "asbestiform" describes a mineral habit; it is a way something grows in nature, and is applied to an array o f minerals. Asbestiform is a material with the geometry o f a fiber or matted mass that is easily split into long, thin flexible fibers. The American Society for Testing and Materials (ASTM) definition o f asbestiform is as follows: "Asbestiform mineral fiber populations generally have the following characteristics when viewed by light microscopy: (1) many particles with aspect ratios ranging from 20:1 to 100:1 or higher (greater than 5 pm in length); (2) very thin fibrils generally 2 See comments submitted by Dr. Ann Wylie, Professor, University o f Maryland; and John Addison (John Addison Consultancy) and Dr. Arthur M. Langer (Professor, The City University of New York). Presentations by Dr. Wylie and Mr. Addison, and by Dan Crane, OSHA, at the BSC meeting, also provided clarification/corrections. 3Pooley, F.D. and Rowlands, N. (1977) Chemical and Physical Properties o f British Talc Powders. In: Walton, W.H. and McGovern, B., eds., Inhaled Particles, Vol. IV, Part 2, Oxford, Pergamon Press, pp. 639-646. Page 3 Dr. C.W. Jameson April 24, 2001 less than 0.5 pm in width; and (3) in addition to the mandatory fibrillar crystal growth, two or more o f the following attributes: (a) parallel fibers occurring in bundles, (b) fibers displaying splayed ends, (c) matted masses o f individual fibers, and (d) fibers showing curvature." The definitions presented above have been concurred with by Mr. Dan Crane, Occupational Safety and Health Agency, and Mr. John Addison, former Head o f the Mineralogy Section at the Institute o f Occupational Medicine, Edinburgh. The NTP background document contained erroneous information which prevented a valid assessment o f the carcinogenicity o f talc. Upon review o f the transcript from the BSC meeting, it is clear that clarification of the mineralogy, morphology and terminology o f the mineral "talc" and the mineral habit "asbestiform" was critical to the final vote on the listing o f talc in the 10thReport on Carcinogens. It should be noted that the correct information regarding the terms "talc" and "asbestiform" was not available to the RG1 and RG2 committees, which explains the inconsistent recommendations regarding the listing of talc. The documents previously submitted to NTP addressing the basis of the nomination show conclusively th a t the listing of talc not containing asbestiform fibers in the 10th R eport on Carcinogens is not scientifically justified. In response to the NTP draft report, CTFA and others submitted detailed comments addressing the basis of the proposed listing. Arguments against listing talc not containing asbestiform fibers as "reasonably anticipated to be a human carcinogen" are briefly summarized here: - The epidemiologic evidence does not support a causal association between talc use and ovarian cancer.4 The dose-response pattern among talc users is inconsistent, and overall shows an inverse trend for both duration of use and frequency of use.5 A plausible biological mechanism is lacking to explain a causal relationship. The majority o f these studies were not specifically designed to test the hypothesis that talc use contributes to ovarian cancer. 4 Three reviews o f the epidemiology studies re: talc and ovarian cancer were submitted by CTFA. The reviews were authored by Dr. Kenneth Rothman, (Professor, Department o f Epidemiology and Medicine, Boston University), Dr. Harris Pastides (Dean, School o f Public Health, University o f South Carolina), and Dr. Jonathan Samet (Chairman, Department o f Epidemiology, Johns Hopkins University); Dr. Samuel Shapiro, Emeritus Director, Boston University o f Public Health; and Joshua Muscat, M.P.H., American Health Foundation. 5 See review "Interpretation o f Epidemiologic Studies on Talc and Ovarian Cancer" by Drs. Rothman, Pastides and Samet, Dose-response trends, pages 5-7. Submitted to NTP by CTFA. Page 4 Dr. C.W. Jameson April 24, 2001 The finding o f a small increase in relative risk could be due to several potential confounding factors. Because these studies were largely retrospective studies and the applications o f concern had occurred many years earlier, the composition o f the material being used was not known and could have contained constituents and/or contaminants other than talc. A serious limitation o fthe data is that the true exposure o f ovarian tissue to talc is by necessity unknown, and can only be poorly estimated using proxy measures (i.e., self-reporting o f talc use in the perineal area). Additionally, use o f talc-dusted diaphragms, which would clearly result in female reproductive tract exposure to talc, did not result in an increased relative risk of ovarian cancer (meta-analysis resulted in a summary odds ratio o f 0.79).6 The Federal Register notice states in relation to the BSC meeting outcome for talc not containing asbestiform fibers that "(T)he Subcommittee did not consider die ovarian cancer studies in the evaluation o f talc not containing asbestiform fibers because it was unclear if the talc used in these studies might have been contaminated with asbestos." That statement does not accurately reflect the entire discussion. While the issue o f possible asbestos contamination was raised, issues such as dose-response and biological plausibility were considered and debated at length, as can be verified by the meeting transcript7 (for example, see pages 351-352). It is therefore clear that Subcommittee members did consider the ovarian cancer studies, and that questions about the interpretation o f the epidemiology studies were not limited to questions about the presence o f asbestos in talc. It is very important that this information is not lost as this nomination goes forward. The 1993 NTP chronic rat inhalation study was cited as evidence for the listing o f talc not containing asbestiform fibers in the 10thReport on Carcinogens. However, the high dose used in this study resulted in an overloading o f the rat lungs with talc particles, overwhelming lung clearance mechanisms. This ultimately resulted in the the formation o f lung tumors in females (only) at the highest dose (only). The tumor response is consistent with that observed in rats exposed by inhalation to high levels o f other low toxicity, poorly soluble particles and is not relevant to human talc exposure. These conclusions are discussed at length in submissions to NTP which were made prior to the BSC meeting.8 6 See epidemiology review by Joshua Muscat, point #1, Testing the talc hypothesis using different epidemiologic measures. Submitted to NTP by CTFA. *7 Condensed Transcript, National Toxicology Program (NTP), Board o f Scientific Counselors Report on Carcinogens (RoC) Subcommittee Meeting, December 14, 2000 g See comments submitted by Dr. Donald Dungworth, Professor (emeritus), University of California, Davis (submitted by CTFA); and by Dr. Gunter Oberdorster, Professor, University of Rochester (submitted by Colipa, the European Cosmetic, Toiletry, and Perfumery Association). Dr. Oberdorster has also published on this subject (The NTP Talc Inhalation Study: A Critical Appraisal Focused on Lung Particle Overload. Regulatory Toxicology and Pharmacology [1995] Vol. 21, p. 233-241). Page 5 Dr. C.W. Jameson April 24, 2001 The public comments submitted in response to the NTP draft report were acknowledged at the BSC meeting as providing valuable information, and were not available to the two previous committees (RG1 and RG2) reviewing talc not containing asbestiform fibers. One o f the three principle reviewers o f talc specifically noted that the scientific evidence in the public comments and presentations caused her to change her recommendation from "reasonably anticipated to be a human carcinogen" to "not list".9 In summary, talc not containing asbestiform fibers does not meet the standard as "reasonably anticipated to be a human carcinogen." The BSC agreed with this conclusion and voted 7-3 to not list talc not containing asbestiform fibers in the 10thReport on Carcinogens. CTFA appreciates the opportunity to submit comments on the proposed listing. Sincerely, Gerald N. McEwen, Jr., Ph.D., J.D. Vice President - Science 9 Condensed Transcript, National Toxicology Program (NTP), Board o f Scientific Counselors Report on Carcinogens (RoC) Subcommittee Meeting, December 14, 2000, pages 280-281. 5- -