Document 6wkg6a0nexo3OkQD8ooZ2KGo1

FILE NAME Talc TALC DATE 2002 Mar 18 DOC TALC166 DOCUMENT DESCRIPTION Letter from the CTFA to the US Dept of Health and Services with Journal Article Attached EFiled Jul 09 2013 AMEDT Transaction ID 53169396 THE COSMETIC TOILETRY AND FRAGRANCE ASSOCIATION March 18 2002 E. EDWARD KAVANAUGH PRESIDENT Dr. Kenneth Olden Director National Toxicology Program and National Institute of Environmental Health Sciences U.S. Department of Health and Human Services P.O. Box 12233 Research Triangle Park NC 27709 Dear Dr. Olden The Cosmetic Toiletry and Fragrance Association CTFA appreciates the opportunity to submit further information on talc not containing asbestiform fibers following NTP's deferral on the decision to list in the Report on Carcinogens The enclosed information is submitted in response to the offer of collaboration which you extended in your July 9 letter In an attempt to clarify issues that were raised in the initial Draft Background Document DBD in discussions at the RoC Subcommittee meeting and in your letter of July 9th we have completed an updated review and analysis of the literature Our findings include some 90 studies articles and commentaries more than 50 of which the ones preceded by an asterisk are not referenced in the initial DBD While not all of the additional references may meet NTP criteria for use in a DBD we believe that they provide useful information relevant to the subject matter A summary of our findings from this further review including the literature references is contained in the Attachment to this letter Our review during the 10th RoC proceedings together with this additional literature review indicates that the scientific literature on which the initial RoC nomination for asbestiform talc was based was incomplete and that findings in the DBD are unsupported on certain key points analysis of the pertinent literature further supports our confidence in the safety of cosmetic talc While we do not intend to represent that our literature research is totally exhaustive at this point we do believe it is balanced and that it raises or highlights significant points that deserve further attention as NTP reviews this matter 17TH ST W. SUITE 300 WASHINGTON O.C 20036-4702 202.331,1770 FAX 202 331 1969 http://www.cifa.org http://www.cifa.org http://www.cifa.org SECURING THE INDUSTRY'S FUTURE SINCE 1894 Page 2 Again CTFA appreciates the opportunity to provide input on talc We continue to be open to further discussion including meeting with you at your convenience Please let us know if there is additional information that we can provide Sincerely fTfenes-- Gerald N. McEwen Jr. Ph.D. J.D. Vice President - Science March 11 2002 CTFA ATTACHMENT A Supplemental Analysis of Cosmetic Talc Issues and Literature Evidence Regarding Ovarian Cancer Risk Cosmetic talc vs. asbestos In 1976 CTFA promulgated a specification for cosmetic talc to ensure that it is free of asbestos As a practical matter that specification is enforcing Asbestos has been listed as a known human carcinogen is highly regulated and no consumer products company would knowingly run the risk of asbestos being present in its product even in minute quantities This is a matter both of public perception and potential litigation exposure Therefore both suppliers and end users go to great lengths to assure that the CTFA specification is met In some cases cosmetic talc producers augment the quality assurance process by utilizing additional detection precautions such as transmission electron microscopy The literature clearly does not support the statements that were originally made in the DBD and in many of the epidemiologic studies that talc has a mineralogical and chemical similarity to asbestos and that this similarity supports the biological plausibility of the findings of weak associations in the epidemiologic studies of ovarian cancer E.g. DBD at 24 28. This was a central point of dispute by the commenters in the RoC Subcommittee meeting Dr. A.P.Wehner has commented Talc is as similar to asbestos as graphite is to diamond 84 detrmine Krause and Ashton by way of explaining that chemical composition does not in any way by itself determine the properties of a substance have used the metaphor that a pearl calcium carbonate is not a piece of chalk calcium carbonate 49 Rather the biological effects of a substance are determined by a combination of chemical composition morphology and molecular structure Id Zazenski et al have clearly explained and illustrated the great dissimilarities between pure talc and asbestos in terms of morphology chemical structure and surface properties 92 When considered in its totality pure talc bears little to no resemblance to asbestos The idea that talc is like asbestos repeated many times in the literature and the DBD without critical examination has done considerable harm to the industry The dissimilarities between pure talc and asbestos are borne out by the extensive literature on the biological effects of the substances Asbestos has long been listed since the 1st RoC in 1980 as a known human carcinogen and has shown clear carcinogenic action in both humans and animals Asbestos is known to induce pleural and respiratory system cancers While its exact carcinogenic mechanism has not been determined and probably involves several different effects it has demonstrated cancer promotion activity in experimental animals and in vitro including induction of chromosomal changes aneuploidy and cell transformation 4 79 These biological effects of asbestos have been attributed to its fibrous structure and dimensions as well as properties such as fiber durability and physiochemical surface properties Id and 52 Such properties differentiate asbestos from pure talc and talc associated with calcite dolomites etc. There is also epidemiologic evidence for a relationship between asbestos exposure and ovarian cancer 6 47 This evidence is consistent with the other epidemiologic and mechanistic evidence concerning asbestos carcinogencity For talc on the other hand putting aside for the moment the issue of the ovarian cancer epidemiologic studies there is a distinct lack of evidence of carcinogenic activity Talc is recognized as a fibrotic and sclerosing agent at a high enough dose in the lungs bronchia and pleura and has been implicated as causing granulomas in the peritoneum when introduced via surgeons gloves in the past In clear contrast to asbestos however pure talc has not been associated with human respiratory pleural or peritoneal cancers Nor has its use in pharmaceuticals been associated with cancer in the gastrointestinal ~fi March 11 2002 CTFA ATTACHMENT tract other organs To the contrary pure tale has been accepted in the medical community for decades as a highly effective agent for therapeutic pleurodesis i.e. with no indication of carcinogenic activity of malignant pleural effusion and pneumothorax with no observed risk of cancerous activity 86 Additionally talc has not been shown to have potential carcinogenic activity in animal or in vitro experiments While it has been hypothesized that tale fibrosis in the ovaries due to use of talc on condoms could lead to ovarian cancer 46 there have been no observations of ovarian fibrosis associated with ovarian cancer Evaluation of the Ovarian Cancer Epidemiologic Studies Several of the generally accepted Bradford Hill evaluation factors for judging the credibility of a causal relationship appear to have received insufficient attention to this point With regard to strength the statistical associations observed have been weak generally well under 2.0 with the majority of findings lacking statistical significance Also a number of commenters as well as study authors themselves have observed the distinct absence of a clear response trend in most of the studies Dr. Ernst Wynder one of the founding practitioners of epidemiology in the U.S. and a colleague Muscat JE commented specifically on this point noting that lack of a clear response is particularly significant in the case of consistently weak associations since it is likely to indicate presence of a consistent bias 54 The potential for recall bias in control studies is well recognized Id Muscat and Wynder id have pointed out that in the ovarian cancer control studies there is very wide variability in the percentage of controls reporting use of talc for perineal dusting and that this indicates a lack of reliability in the subject's recall and reporting In the ten control studies of U.S. subjects we found that the percentage of controls reporting perineal dusting ranged from % to 46 This is in line with the range found by Muscat and Barish of approximately % to 50 53 The subjects consistent reporting of slightly more use of perineal dusting than controls despite this wide variation in reported use raises a very strong suspicion of consistent recall bias The conclusion in the DBD at iii and v that bias is unlikely is not supported The failure of Cramer et al to find a trend of higher reported usage in the more recent studies given as a reason for such a conclusion DBD at 28 does not address this point made by Barish Muscat and Wynder The high amount of publicity surrounding the allegations of asbestos in tale in the 1970s and subsequent epidemiologic study reports provides a very plausible basis for such a recall bias In addition to the lack of strength lack of response trend and likelihood of bias we also believe the Hill factors of consistency and biological plausibility require more attention Consistency The discussion in the DBD and the RoC Subcommittee meeting focused almost exclusively on the consistency among a majority of epidemiologic study findings with regard to use of powders in the perineal area although the RG1 and RG2 findings of consistent association appeared to also include use of talc on sanitary napkins and diaphragms At iii and v Such a conclusion regarding those other modes of exposure is not supported The study results were far from consistent for talc on sanitary napkins talc on diaphragms and tale on condoms All of these modes of exposure would more plausibly expose the ovaries to talc than external dusting The translocation issue is discussed below For talc on sanitary napkins nine studies reported results Four reported results below the null nonsignificant 87 14 25 91 and five reported increases ranging from 1.3 to 4.8 one result significant one barely significant 12 17 19 69 56 March 11 2002 CTFA ATTACHMENT For tale on diaphragm or cervical cap eight studies reported results or conclusions Three reported results at or below the null significant 36 27 56 one relied on two previous studies for considering the risk to be significant 19 one reported a RR of 3.0 significant 69 one a RR of 1.5 nonsignificant 87 one a RR of 1.2-1.6 significant 17 and one a RR of 1.1 significant 34 For talc on condoms four studies reported results or conclusions Two of these studies reported no elevation in risk 17 27 one relied on previous studies in considering that there was no significant risk 19 while one reported a significant RR of 1.6 69 Considering all modes of exposure examined in the studies there was pronounced inconsistency in the findings Biologic plausibility As discussed above there is a notable lack of mechanistic evidence for the carcinogenicity of tale supporting the findings in the control studies of ovarian cancer and the mechanistic evidence argues strongly against biologic plausibility The absence of consideration of this point in connection with the epidemiologic data in the DBD is surprising in view of the NTP emphasis on consideration of mechanistic data in the last several years Most of the discussion in the DBD focused on the biologic plausibility of whether tale can translocate from the external perineal region to the ovaries not whether there is mechanistic evidence supporting the biologic plausibility that exposure of the ovaries to talc will cause cancer In considering the issue of translocation there are basically three components 1 Observations of the presence of talc in the ovaries or ovarian tumors 2 findings from controlled experiments designed to test for translocation and 3 findings of reduced risk of ovarian cancer in epidemiologic studies of subjects who had undergone tubal ligation or hysterectomy We will address each of these briefly 1 The observations by Henderson et al in 1971 of talc particles embedded in ovarian tumors led to the hypothesis that talc might be related to ovarian carcinogenesis although Henderson et al did not propose such a hypothesis 42 43 They also reported finding even larger quantities of talc in healthy ovaries A more recent study showed the presence of talc particles in the ovaries of all of both supposedly unexposed and perineally exposed subjects although some of the unexposed subjects appeared to have been exposed during diapering 40 Asbestos fibers have also been found in ovarian tumors and malignant peritoneal mesotheliomas of women who had no recorded asbestos exposure history 38 2 Experiments attempting to test the hypothesis that tale or other particles can translocate from the vagina to the ovaries have produced conflicting results and experimenters who have found no translocation have offered explanations for the opposing findings 21 77 3 A number of epidemiologic control studies have consistently found a reduced risk of ovarian cancer in women who have undergone tubal ligation or hysterectomy and had been exposed to cosmetic talc However at least one study has also found significantly reduced risk in cases that had not reported being exposed to cosmetic tale 31 Some have hypothesized that such surgical procedures block external environmental agents such as talc or asbestos from entering the ovaries However this has not been the sole or even the preferred hypothesis It has also been hypothesized that since there is now a considerable body of evidence indicating that ovarian cancer risk is influenced by hormonal and ovulatory factors reduced risk from such procedures could be due to disruption of ovulation and certain hormone levels 70 It has also been noted that such procedures could result in incidental removal of cancerous tissue 75 3 March 11 2002 CTFA ATTACHMENT Thus it seems clear that some talc particles as well as asbestos fibers can reach the human ovaries however how this occurs is still unclear It has not been established that talc particles can reach the human ovaries through vaginal translocation as a result of perineal exposure and there is some evidence that talc as well as other mineral particles of low toxicity and low solubility can be transported to various internal organs through the human body's systemic circulation 85 Of course the mere presence of talc in the ovaries does not indicate that it is a cause of ovarian cancer and there is not a biologically plausible explanation for cancer causation by pure talc Historical contamination of cosmetic tale with asbestos Two studies one in 1968 and one in 1976 reported finding fibrous materials and asbestos in the- shelf consumer talc products 16 68 In the latter study half the brands had detectable asbestos This occurred at a time when evidence was accumulating concerning the human carcinogencity of asbestos Although there were doubts concerning the validity of the studies 49 and given the tack of previous awareness of the dangers of asbestos it is quite possible that there was in fact asbestos contamination in some brands of cosmetic talc powders prior to 1976. Recognizing this CTFA promulgated its specification for cosmetic talc in 1976 which required a complete absence of detectable asbestos in cosmetic talc A review of the epidemiologic studies on ovarian cancer and talc exposure shows that a large portion of the exposures in all of the studies must have occurred prior to 1976. In addition none of those studies were able to characterize the composition of the powders or identify brands Thus in addition to the analytical weaknesses discussed previously the exposures might have involved exposure to asbestos making the studies essentially lacking in utility and data quality for the purpose of evaluating the safety of present cosmetic talc Conclusion Present cosmetic talc must be assumed to be free of asbestos consistent with the CTFA specification and absent evidence to the contrary It is simply a marketplace requirement The current biologic evidence is overwhelming that pure cosmetic talc is not a risk factor in inducing cancer Epidemiologic findings concerning ovarian cancer and cosmetic talc are extremely weak equivocal and cannot be considered relevant to present cosmetic tale Consequently at present we do not see any way to define cosmetic tale in a manner that would support a RoC listing nomination March 11 11 2002 CTFA ATTACHMENT REFERENCES Indicates material not referenced in the Draft Background Document * Acheson E Gardner MJ Pappard EC and Grime LP 1992. Mortality of two groups of women who manufactured gas masks from chrysotile and crocidolite asbestos A year follow BrJ Med 39 344-48 2 *4, 5 6 7 8 9 10 11 12 13 14 15 Anonymous 1977. Cosmetic talc powder editorial Lancet 1348-49 Anteby SO Mos Yosef S. and Schenker JC 1983. Ovarian cancer Geographical host and environmental factors - An overview Arch Gynecol 234 2 131-48 Barrett JC Lamb PW and Wiseman RW 1989. Multiple mechanisms for the carcinogenic effects of asbestos and other mineral fibers Environ Health Perspect 81 81-89 Barrett JC 1994. Cellular and molecular mechanisms of asbestos carcinogenicity Implications for biopersistence Environ Health Perspect 102 Supp 5 19-23 Berry G Newhouse ML and Wagner JC 2000. Mortality from all cancers of asbestos factory workers in east London 1933-80 Occup Environ Med 57 11 782-85 Blejer HP and Arlon R. 1973. Talc A possible occupational and environmental carcinogen J Occup Med 15 2 92-97 Blount AM and Vassiliou AH 1983. Identification of chlorite and serpentine in cosmetic or pharmaceutical talc Environ Health Perspect 51 379-85 Blount AM 1991. Amphibole content of cosmetic and pharmaceutical talcs Perspect 94-225-30 Environ Health Booth M Beral V Smith P. 1989. Risk factors for ovarian cancer A control study Br J Cancer 60 592-598 Campos JRM Werebe EC Vargas FS Jatene FB Light RW insufflated talc research letter Lancet 349 9047 251-52 1997. Repiratory failure due to Chang S and Risch HA 1997. Perineal talc exposure and risk of ovarian carcinoma Cancer 79 2396-2401 Chen Y Wu PC Lang JH Ge WJ Hartge P and Brinton LA 1992. Risk factors for epithelial ovarian cancer in Beijing China Int J Epidemiol 21 23-29 Cook LS Kamb ML and Weiss NL cancer Am J Epidemiol 145 459-465 1997. Perineal powder exposure and the risk of ovarian Comelison TLK Natarajan N Piver MS and Mettlin CJ ovarian carcinoma Cancer Detect Prev 21 1-6 1997. Tubal ligation and the risk of March 11 2002 ATTACHMENT 18 19 20 Cralley LJ Key MM Groth DH Lainhart WS and Ligo RM 1968. Fibrous and mineral content of cosmetic talcum products Am Ind Hyg Assoc / 29 4 350-54 Cramer DW Welch WR Scully RE and Wojciechowski CA. 1982. Ovarian cancer and tale A control study Cancer 50- 372-376 Cramer DW 1999. Perineal talc exposure and subsequent epithelial ovarian cancer letter Obstet Gynecol 94 ) 160-61 Cramer DW Liberman RF Ernstoff L Welch WR Greenberg ER Baron JA and Harlow BL 1999. Genital talc exposure and risk of ovarian cancer J Int Cancer 81 351-356 Daly M and Obrams Gl Oncol 25 255-64 1998. Epidemiology and risk assessment for ovarian cancer Semin 21 22 23 24 25 26 27 28 DeBoer CH 1972. Transport of particulate matter through the human female genital tract Reprod Fert 28 295-97 Dement JM 1984. Letter re fiber in New York talc - responding to letter from Dunn JR apparently Chairman of Schering Corp. Am Ind Hyg Assoc 45 4 B to 9 Egli GE and Newton M. 1961. The transport of carbon particles in the human female reproductive tract Fertil Steril 12 151-55 Germani D Belli S Bruno C Grignoli M Nesti M Pirastu R Comba P. 1999. Cohort mortality study of women compensated for asbestosis in Italy Am J Ind Med 36 129-34 Gertig DM Hunter DJ Cramer DW Colditz GA Speizer FE Willett WC and Hankinson SE 2000. Prospective study of talc use and ovarian cancer J Natl Cancer Inst 92 249-252 Godard B. Foulkes WD Provencher D Brunet JS Tonin PN Masson AM Narod SA and Ghadirian P. 1998. Risk factors for familial and sporadic ovarian cancer among French Canadians A control study Am J Obstet Gynecol 179 403-10 Green A Purdie D Bain C Siskind V Russell P. Quinn M and Ward B. 1997. Tubal sterilisation hysterectomy and decreased risk of ovarian cancer Int J Cancer 6 71 948-51 Grexa RW and Parmentier CJ 1979. Cosmetic tale properties and specifications Cosmetics & Toiletries 94 29-33 29 30 31 Gross AJ and Berg PH 1995. A analytical approach examining the potential relationship between talc exposure and ovarian cancer J Expo Anal Environ Epidemiol 5 181-95 Hamer DH Rolle FR and Schelz JP Am Ind Hyg Assoc J 5 37 296-304 1976. Characterization of talc and associated minerals Hankinson SE Hunter DJ Dolditz GA Willett WC Stampfer MJ Rosner B Hennekens CH and Speizer FE Tubal ligation hysterectomy and risk of ovarian cancer A prospective study 1993 JAMA 270. 2813-18 March 11 2002 CTFA ATTACHMENT 32 Comments on above article by Hankinson et al JAMA 71 16 1235-37 Myers ER and Silver LS 1994. Letter 33 Harlow BL and Weiss NS 1989. A control study of borderline ovarian tumors The influence of perineal exposure to talc Am J Epidemiol 130 390-394 Harlow BL Cramer DW Bell DA and Welch WR 1992. Perineal exposure to talc and ovarian cancer risk Obstet Gynecol 80 19-26 35 Harlow BL and Hartge PA 1995. A review of perineal talc exposure and risk of ovarian cancer Regul Toxicol Pharmacol 21 254-60 36 Hartge P. Hoover R Lesher LP and McGowan L. 1983. Talc and ovarian cancer letter JAMA 250. 1844 37 38 39 Hartge P and Stewart P. 1994. Occupation and ovarian cancer a control study in the Washington DC metropolitan area 1978-1981 J Occup Med 36 924-27 Heller DS Gordon RE Clement PB Turnnir R and Katz N. 1999. Presence of asbestos in peritoneal malignant mesotheliomas in women IntJ Gynecol Cancer 9 452-55 Heller DS Gordon RE Westhoff C. and Gerber S. burden Am J Indust Med 29 435-39 1996. Asbestos exposure and ovarian fiber 40 41 42 43 44 45 46 Heller DS Westhoff C Gordon RE and Katz N. 1996. The relationship between perineal cosmetic tale usage and ovarian talc particle burden Am J Obstet Gynecol 174 1507-1510 Heller DS Gordon RE Katz N. 1999. Correlation of asbestos fiber burdens in fallopian tubes and ovarian tissue Am J Obstet Gynecol 181 2 346-47 Henderson WJ Joslin CA Turnbull AC and Griffiths K. and cervix J Obstet Gynecol Br Commonw 78 226-72 1971. Talc and carcinoma of the ovary Henderson WJ Hamilton TC and Griffiths K. 1979. Talc in normal and malignant ovarian tissue letter Lancet 1 8114 499 Hildick GY 1976. The biology of talc BrJ Ind Med 33 4 217-29 H~-ldickG. 1977 Letter J Toxicol Environ Health 2 5 1221-22 Kasper CS and Chandler PJ 1995. J Amer Med Ass 273 846-47 Possible morbidity in women from talc on condoms letter 47 48 Keal EE 1960. Asbestos and abdominal neoplasms 2 Lancet 1211-16 Krause JB 1977. Mineralogical characterization of cosmetic talc products letter Envrion Health 2 5 1223-26 Toxicol March 11 2002 CTFA ATTACHMENT 49 50 Krause JB and Ashton WH 1978. Misidentification of asbestos in talc In National Bureau of Standards Special Publication 506 Proceedings of the Workshop on Asbestos Definitions and Measurement Methods NBS Gaithersburg MD July 180-20 1977 pp 339-52 Longo DL and Young RC 1979. Cosmetic talc and ovarian cancer Lancet ii 349 51 52 Marconi A Maccione M Rossi L. 1986. Asbesto E. Talco Determinazione del contenuto di particelle minerali fibrose in polveri di talco commerciali mediante tehcniche associate di microscopia ottica Asbestos and tale Determination of mineral fibre content in commercial tale using combined optical microscope techniques Med Lav 77 5 496-510 Mossman B Light W Wei E. 1983. Asbestos Mechanisms of toxicity and carcinogenicity in the respiratory tract Annu Rev Pharmacol Toxicol 23 595-615 53 Muscat JE and Barish M. 1998. Epidemiology of talc exposure and ovarian cancer A critical assessment Comments Toxicol Special Issue on Talc 6 5 327-35 54 Muscat JE and Wynder EL 1997 Re Perineal powder exposure and the risk of ovarian cancer letter Am J Epidemiol 146 9 786 55 Natow AJ 1986. Talc Need we beware Cutis 37 5 328-29 56 Ness RB Grisso JA Cottreau C Klapper J Vergona R Wheeler JE Morgan M and Schlesselman JJ 2000. Factors related to inflammation of the ovarian epithelium and risk of ovarian cancer Epidemiology 11 111-117 57 Ness RB and Cottreau C. 2000. Response re possible role of ovarian epithelial inflammation in ovarian cancer letter J Natl Cancer Inst 92 163 58 Newhouse ML Berry G Wagner JC and Turok ME asbestos workers Brit J Indus Med 29. 134-41 1972. A study of the mortality of female 59 Paoletti L Caiazza S Donelli G and Pocchiari F. 1984. Evaluation by electron microscopy techniques of asbestos contamination in industrial cosmetic and pharmaceutical talcs Regul Toxicol Pharmacol 4 3 222-35 60 Parazinni F Freseschi S Vecchia D and Fasoli M. review Gynecol Oncol 43 9-23 1991. The epidemiology of ovarian cancer 61 Parmentier CJ and Gill CJ 1978. Practical aspects of talc and asbestos In National Bureau of Standards Special Publication 506 Proceedings of the Workshop on Asbestos Definitions and Measurement Methods NBS Gaithersburg MD July 180-20 1977 pp 403-11 62 Phillips JC Young PJ Hardy J and Gangolli SD 1978. Studies disposition of labelled talc in the rat mouse guinea and rabbit 161-63 on the absorption and Fd Cosmet Toxicol 16 63 Phillipson IM 1980. Talc quality letter Lancet 1 8158 48 March 11 2002 CTFA ATTACHMENT 65 Purdie , Green A Bain C Siskind V Ward B. Hacker N Quinn M Wright G Russell P and Susil B. 1995. Reproductive and other factors and risk of epithelial ovarian cancer An Australian control study Survey of Women's Health Study Group Int J Cancer 62 678-684 Research Committee of the Pneumoconiosis Unit 1979. J Dis Chest 73 285-88 British Thoracic Association and the Medical Research Council A survey of the term effects of talc and kaolin pleurodesis Br 66 67 68 69 70 71 72 73 74 75 76 77 78 Rohl AN 1974. Asbestos in talc Environ Health Perspec9t 129-32 Rohl AN and Langer AM Health Perspect 9 95-109 1974. Identification and quantitation of asbestos in talc Environ Rohl AN Langer AM Selikoff I Tordini A Klimentidis R Bowes DR and Skinner DL 1976 Consumer talcums and powders Mineral and chemical characterization Toxicol Environ Health 2 2 255-84 Rosenblatt KA Szklo M and Rosesshein NB 1992 development of ovarian cancer Gynecol Oncol 45 20-25 Mineral fiber exposure and the Rosenblatt KA and Thomas DB 1996. Reduced risk of ovarian cancer in women with tubal ligation or hysterectomy The World Health Organization Collaborative Study of Neoplasia and Steroid Contraceptives Cancer Epidemiol Biomarkers Prev 5 11 933-35 Russell RS Merz RD Sherman WT and Silvertson JN 1979. particles in talcum powder Fd Cosmet Toxicol 17 117-22 The determination of respirable Shoham Z. 1994. Epidemiology etiology and fertility drugs in ovarian epithelial carcinoma Where are we today Fertil Steril 62 433-448 Shushan A Taltiel O Iscovich J Elchalkal U Peretz T and Schenker JG 1996. menopausal gonadotropin and risks of epithelial ovarian cancer Fertil Steril 65 13-18 Human Tavani A Negri E Franceschi S Parazzini F La Vecchia C. 1993. Risk factors for epithelial ovarian cancer in women under age 45. EurJ Cancer 29A 9 1297-12301 Tortolero G Mitchell MF and Rhodes H. 1994. ovarian cancer Obstet Gynecol Clinics N Amer 21 ( 1-23 Epidemiology and screening of Tzonou A. Polychronopoulou A Hsieh CC Rebelakos A Karakatsani A and Trichopoulos D. 1993. Hair dyes analgesics tranquilizers and perineal talc application as risk factors for ovarian cancer Int J Cancer 55 408-410 Venter PE and Iturralde S. 1979. Migration of a particulate radioactive tracer from the vagina to the peritoneal cavity and ovaries S Afr MedJ 55 917-19 Vigliani EC Ghezzi I Maranzana P Permis B. northern Italy Med Lav 59 8 481-85 1969. Epidemiology study of asbestos workers in March 11 2002 ATTACHMENT 79 Voytck P Anver M Thorslund T Conley J and Anderson E. 1990. Mechanisms of asbestos carcinogenicity J Am Coll Toxicol 9. 541-546 80 81 Walker C Everitt J Barrett JC 1992. Possible cellular and molecular mechanisms for asbestos carcinogenicity Am J Ind Med 21 2 253-73 Wehner AP Hall AS Weller RE Lepel EA and Schirmer RE 1985. Do particles translocate from the vagina to the oviducts and beyond Fd Chem Toxicol 23 367-72 82 83 84 Wehner AP Weller RE and Lepel EA 1986. On talc translocation from the vagina to the oviducts and beyond Fd Chem Toxicol 24 329-38 Wehner AP 1994. Biological effects of cosmetic talc Food Chem Toxicol 32 1173-84 Wehner AP 1998. 66 Is cosmetic talc safe Comments Toxicol Special Issue on Talc 5 6 336- 85 Werebe EC Pazetti R De Campos JRM Fernandez PP Capelozzi VL Jatene FB and Vargas FS 1999. Systemic distribution of talc after intrapleural administration in rats Chest 115 1 190-93 86 Weissberg D and Zeev I. Card Surg 106 4 689-95 1993. Talc pleurodesis Experience with 360 patients J Thor 87 Whittemore AS Wu ML Paffenbarger RS Jr. Sarles DL Kampert JB Grosser S Jung DL Ballon S and Hendrickson M. 1988. Personal and environmental characteristics related to epithelial ovarian cancer II Exposures to talcum powder tobacco alcohol and coffee Am J Epidemiol 128 1228-1240 88 Whittemore AS Harris R Itnyre J and the Collaborative Ovarian Cancer Group 1993 Characteristics relating to ovarian cancer risk Collaborative analysis of 12 US control studies II Invasive epithelial ovarian cancers in white women Am J Epidemiol 137 8 928- 29 89 Whysner J. and Mohan M. 2000. Perineal application of talc and cornstarch powders Evaluation of ovarian cancer risk Am J Obstet Gynecol 3 182 720-724 90 Wignall BK and Fox AJ 34-38 1982. Mortality of female gas mask assemblers Br J Indus Med 39 91 92 93 Wong C Hempling RE Piver MS Natarajan N and Mettlin CJ 1999. Perineal talc exposure and subsequent epithelial ovarian cancer A control study Obstet Gynecol 93 372-376 Zazenski R Ashton WH Briggs D Chudkowski M Kelse JW MacEachern L. McCarthy EF Nordhauser MA Roddy MT and Teetsel NM 1995. Talc Occurrence characterization and consumer applications Regul Toxicol Pharmacol 21 218-29 Zazenski RJ 1998. tale 5 6 313-26 The commercial significance of talc Comments Toxicol Special Issue on 10