Document zQndyM9woY6Ddak4jpDGjp7va

FILE NAME Talc TALC DATE 1996 DOC TALC045 DOCUMENT DESCRIPTION Journal Article - Asbestos Exposure and Ovarian Fiber Burden AMERICAN JOURNAL OF INDUSTRIAL MEDICINE 435 4319996 Asbestos Exposure and Ovarian Fiber Burden Debra S. Heller MD Ronald E. Gordon PhD Carolyn Westhoff MD and Susan Gerber MD Epidemiologic studies suggest increased risk of epithelial ovarian cancer in female asbestos workers and increased risk of malignancy in general in household contacts of asbestos workers Ovaries were studied from 13 women with household contact with men with documented asbestos exposure and from 17 women undergoing incidental oophorectomy Ovar- ian tissue was examined by analytic electron microscopy Significant asbestos fiber burdens were detected in 9 out of 13 women with household asbestos exposure 69.2 and in 6 out of 17 women who gave no exposure history 35 Three exposed women had asbestos counts over 1 million fibers per gram wet weight 23 but only 1/17 women without an exposure history had a count that high % Although asbestos has been documented as a contaminant of some older cosmetic talc preparations the chrysotile and crocidolite types of asbestos we detected are more indicative of back- ground and occupational exposure This study demonstrates that asbestos can reach the ovary Although the number of subjects is small asbestos appears to be present in ovarian tissue more frequently and in higher amounts in women with a documentable exposure history '1996 Wiley Inc KEY WORDS asbestos ovary talc environmental exposure INTRODUCTION Epidemiologic evidence suggests that there is an in- creased risk of ovarian carcinoma in female asbestos workers Acheson et al 1982 Graham and Graham 1967 Keal 1960 Newhouse et al 1972 1985 Wignall and Fox 1982 and animal data show changes resembling early ovarian carcinoma after intraperitoneal injection of asbestos Graham and Graham 1967 In addition household con- tacts of asbestos workers have been shown to be at in- creased risk of developing asbestos disease Joubert et al 1991 Roggli and Longo 1991 so female household contacts of asbestos workers may also be at risk of ovarian exposure to asbestos There is literature that supports that perineal talc exposure increases the risk of ovarian carci- noma However some of these data have been clouded by the fact that cosmetic talc was often contaminated with asbestos in the past particularly before 1976 Cramer et al 1982 Particulate matter can reach the female peritoneal cavity via the transvaginal route Egli and Newton 1961 Henderson et al 1986 Joubert et al 1991 A woman exposed to her husband's occupationally contaminated laundry may have asbestos enter the peritoneal cavity by passive transfer or even by sexual relations The purpose of this study was to determine whether women exposed to asbestos have a high asbestos fiber burden in their ovaries MATERIALS AND METHODS College of Physicians and Surgeons Columbia University New York New York O.S.H. C.W. S.G. Mount Sinai School of Medicine New York New York R.E.G. Address reprint requests to Debra S. Heller M.D. Gyn Pathology 16-404 College of Physicians & Surgeons 630 West 168th Street New York NY 10032 Accepted for publication July 5 1995 Eligible women were contacted by postcard with the assistance of a law firm specializing in asbestos claims Women with household contact to asbestos as doc- umented by interview and who had themselves previously undergone ovarian surgery were invited to participate No women with direct occupational exposure responded '1996 Wiley Inc. 436 Heller et al TABLE 1. Demographics and Pathologic Findings Among 8 Patients With Household Contacts Evaluated for Asbestos Disease Oophorectomized Between 1973-1994 and 5 Oophorectomized Patients With a History of Asbestos Exposure From the Columbia Presbyterian Medical Center Benign Neoplasm Study 1992-1993 Subject 1 2 3 4 5 Reason for surgery Papillary serous cystadenocarcinoma of ovary Mucinous cystadenocarcinoma of ovary Endometrial adenocarcinoma Atypical hyperplasia of endometrium Endometriosis of ovary Asbestos per gram wet weight 490,813 chrysotile crocidolite 12 below detectible limits 1,227,031 chrysotile crocidolite 11 74,167 chrysotile 328,913 chrysotile Limits of detection 40,901 26,267 15,338 18,542 41,114 6 7 8 9a 10 11" " " Leiomyoma uteri 3,438,636 chrysotile Serous cystadenoma of ovary fibroma of ovary Endometrial adenocarcinoma Cystadenofibroma of ovary Benign epithelial cyst of ovary Serous cystadenoma of ovary Cystadenofibroma of ovary Cystadenofibroma of ovary below detectible limits 1,513,00 chrysotile tremolite 4 49,081 chrysotile crocidolite 1.1 below detectible limits 298,618 chrysotile 788,020 crocidolite below detectible limits 42.983 42,983 37,825 24.541 37.825 | 24,885 157,604 42.983 Asbestos exposure pipefitter with asbestos Father of mesothelioma asbestosis both insulators asbestosis carpenter in a factory insulator died of tung cancer Father and worked in asbestos plant father of lung cancer aunt of asbestosis asbestosis asbestos and insulation worker insulation worker Husband of asbestosis worked as carpenter and with concrete 2 construction workers shipyard worker and school engineer Household member worker x 4 years shipyard worker Household contact -construction 3 years Subjects from Columbia Presbyterian Medical Center Benign Neoplasm Study Women with both benign and malignant disease responded Women undergoing oophorectomy for benign ovarian neoplasms at Columbia Presbyterian Medical Center who were interviewed in depth for another study were available as controls and were included after ascertaining asbestos ex- posure history and availability of nonneoplastic ovarian tissue for analysis These women were chosen for the availability of interviews as well as tissue Five of these women were found to have sustained asbestos exposure There were 13 exposed subjects and 17 women who gave no history of exposure Tissue from two stillborn ovaries was also ana- lyzed Tissue blocks of benign adjacent or contralateral ovarian tissue as available were obtained and analytic elec- tron microscopy was performed according to the subsequent protocol Hematoxylin and eosin stained sections of ana- lyzed tissue were examined There was no evidence of response to asbestos such as foreign body giant cell reactions or fibrosis in the tissue Ovarian tissue does not undergo fibrosis as does lung Analytic Electron Microscopy Protocol Ovarian tissue in blocks was deparaffinized rehydrated blotted dry and weighed Digestion with % KOH was performed at 70 for 2-4 hr After complete diges- tion the tissue was centrifuged at 12,000 rpm for 20 min The KOH was removed leaving a pellet to which approximately 20 ml of distilled water was added The pellet was resuspended by using a microultrasonic cell disrupter at 50 watts for 5 sec Centrifugation distilled water wash and Ovarian Asbestos Fiber Burden 437 TABLE II Demographics and Pathologic Findings Among 17 Oophorectomized Patients With No History of Asbestos Columbia Presbyterian Medical Center Benign Neoplasm Study 1992-1993 Control 11 subjects 1 2 3 4 56 56 Reason for surgery Asbestos fibers per gram wet weight 4 serous cystadenomas cyst 3 benign cystic teratoma ovarii 2 endometrioma 1 fibrothecoma 1 mucinous cystadenoma Endometriosis benign cystic teratoma Endometrioma of ovary Benign cystic teratoma of Ovary Endometrioma of ovary Serous cystadenoma of ovary Benign cystic teratoma of Ovary Below detectable limits 525,871 chrysotile crocidolite 2 109,069 chrysotile crocidolite 11 33,849 chrysotile 147,244 chrysotile crocidolite 12 98,163 crocidolite 2,181,388 chrysotile Limits of detection None greater than 27,267 17,529 6,817 8,462 12,270 12,270 27,267 Exposure history None None None None None None None microultrasonic cell disrupter were repeated 3 times The distilled water was removed and the pellet was resuspended in 5-10 ml of distilled water Ten drops of the final suspension were placed on nickel Formvar and carboncoated locator grids and air dried Transmission electron microscopy to identify fibers and their size was performed The identity of the fibers was determined by dispersive spectroscopy and confirmed by electron diffraction SAED Grids were viewed at both 10,000 and 19,000 diameters All fibers observed were counted Routinely as they are opened or distilled water at each filtering all solutions are checked for detectable limits of asbestos fibers All places where asbestos could have contaminated the specimen such as paraffin are also controlled for paraffin blocks from each different source All solutions are checked by passing the fluids through a m Nucleopore filter to maximize the efficiency of detecting and counting fibers present in these solutions and materials The solutions that are routinely tested are distilled water KOH and xylene If detectable levels of asbestos fibers exist in the solutions used to initially fix and process the tissue because they came from different hospitals at which it was not possible to test these solutions directly they would be detected in the paraffin controls We have yet to identify detectable levels in any of the solutions or paraffin RESULTS A summary of the results can be seen in Tables I and II Nine of the 13 women exposed to asbestos had asbestos in their ovarian tissue 69.23 with 3 23 of them having counts over 1 million fibers per gram of wet weight Among the controls 6/17 women had detectable asbestos in their ovaries 35 with only 1 % patient with a count over 1 million fibers per gram wet weight In addition talc was detected in 11/13 exposed women 85 and in all 17 controls 100 No asbestos or talc was detected in the still- born material All fibers were counted and analyzed for type and size The results of that analysis are summarized in Table III In general the fibers were relatively small with regard to length and narrow in diameter However the great majority of fibers were greater than 3 mwith a minimum aspect ratio of 10 Except for one case in which tremolite was observed the fibers were either chrysotile or crocidolite or both DISCUSSION Epithelial ovarian carcinoma is a major cause of female mortality Greene et al 1984 Epithelial ovarian cancer 438 Heller et al TABLE III Asbestos Fibers in Ovarian Tissues Type Number and Dimensions Subject No. of fibers Fiber type ...m 3-10 long long ...,,0-.1....m | 0.1-0.2 long diameter diameter um diameter 1" 4 Chrysotile 1 2 8 Crocidolite 1 7 3" 40 Chrysotile 2 28 40 Crocidolite 3 31 4" 4 Chrysotile _ 3 5 8 Chrysotile 1 6 QUA 80 Chrysotile 5 62 ga 32 Chrysotile 2 22 8 Tremolite 1 7 ga 1 Chrysotile - 1 1 Crocidolite _ 1 11" 12 Chrysotile 1 9 12 20 Crocidalite 2 14 10 10 Chrysotile - 8 20 Crocidolite 2 18 2b 8 Chrysotile 7 8 Crocidolite - 7 36 4 Chrysotile | 4 4 4 Chrysotile | 4 8 Crocidolite - 7 5b 8 Crocidolite | 8 66 80 Chrysotile ~ 58 1 4 _ 4 10 35 6 30 1 4 1 7 13 K2 8 22 | - | - | 1 2 8 4 12 1 4 _ 17 5 ed 6 ^/llll 3 ^/llll 3 ^/llll 7 ^/llll 6 ^/llll 68 _ 4 5 10 1 9 10 0 | 1 4 8 6 3 3 2 1 1 1 2 12 _ _ _ _ _ _ _ 2 wwwww _ _ www._ ~ _ _ _ _ _ - From Table 1 From Table develops from the surface epithelium of the ovary which is embryologically derived from the same tissue as the mesothelium of the abdominal cavity the celomic epithelium Falkson 1985 Thus ovarian carcinoma and malignant mesothelioma of the peritoneal cavity are believed by some to be related neoplasms Parmely and Woodruff 1974 Asbestos causes malignant mesothelioma and there is evidence to support it as an etiology in ovarian carcinoma as well Acheson et al 1982 Falkson 1985 Graham and Graham 1967 Keal 1960 Newhouse 1979 Newhouse et al 1972 1985 Whittemore et al 1988 Wignall and Fox 1982 Intraperitoneal injection of tremolite asbestos into guinea pigs and rabbits was shown to cause epithelial changes in their ovaries similar to those seen in early ovarian cancer Graham and Graham 1967 These investigators also found birefringent crystalline material near these epithelial changes but no further attempt was made to identify the material No such material was found in controls As- bestos fibers have been shown to be cytotoxic to Chinese hamster ovary CHO cells an epithelioid cell culture line Neugut et al 1978 Several investigators have cited an increased mortality from ovarian cancer in female asbestos workers exposed as gas mask assemblers or other factory workers Acheson et al 1982 Newhouse 1979 Newhouse et al 1972 1985 Wignall and Fox 1982 In addition it is known that household contacts of asbestos exposed workers are also at increased risk of developing malignant disease in general Joubert et al 1991 Roggli and Longo 1991 In study of 52 histologically confirmed malignant mesotheliomas in women most with no occupational exposure of their own a significant number were found to have husbands or fathers who worked in an asbestos industry Vianna_and Vianna_and Polan 1978 and the findings suggested indirect exposure to a husband as the most important factor The fact that exposure to a husband is more significant than exposure to a father suggests a possible role for sexual contact as a transporting vector for asbestos fibers House- hold exposure has been related to the asbestos dust on the workers clothing with risk to those who launder the clothing Joubert et al 1991 While this may be the exposure source in wives as well as in daughters it is possible that sexual contact with a male contaminated with asbestos fi- bers introduces those fibers into the vagina of his partner where they can reach the peritoneal cavity There is evi- Ovarian Asbestos Fiber Burden 439 dence of transport of particulate matter into the female peritoneum by the transvaginal route in both human and animal studies Egli and Newton 1961 Henderson et al 1986 Venter and Iturralde 1979 Whittemore et al 1988 suggested that vaginal exposure to particulate matter such as asbestos and talc was a potential risk factor for intraperitoneal ovarian exposure Her conclusion was based on finding that in exposed women a previous history of hysterectomy or tubal ligation which blocks peritoneal access was protective against ovarian cancer Talc has also been implicated as a possible etiologic agent in ovarian cancer Harlow et al 1989 1992 and this is related to the asbestos problem in several ways Aside from the chemical similarities between the two many cos- metic tales contained significant amounts of asbestos particularly prior to 1976 Cramer et al 1982 The significance of the detection of talc in the majority of the exposed women and in all women giving no exposure history is unclear and further studies are under way to further eluci- date this association CONCLUSIONS In our study the women with a positive exposure history had asbestos detected in their ovaries more frequently and in higher counts None of the exposed subjects in this study was directly occupationally exposed but all were passively exposed to a household contact It is unclear why so many of the women giving no exposure history did have detectable asbestos in their ovanes although it is known that there is a background level of asbestos in the lung tissue of nonexposed individuals All our available control patients were selected from a group of extensively interviewed women with benign ovarian neoplasms Further studies are aimed at women with no ovarian pathology The significance of the finding of asbestos in ovaries requires further investigation ACKNOWLEDGMENTS This work was supported by a grant from the Columbia Presbyterian Cancer Center The authors wish to thank Nor- man Katz for technical assistance Falkson CI 1985 Mesothelioma or ovarian carcinoma A case report S Afr Med J 676 677676 677 Graham J. Graham R 1967 Ovarian cancer and asbestos Environ Res 1.115-128 Greene MH Clark JW Blayney DW 1984 The epidemiology of ovarian cancer Semin Oncol 11 209-226 Harlow BL Cramer DW Bell DA Welch WR 1992 to talc and ovarian cancer risk Obstet Gynecol 19 Perineal exposure 26 Harlow BL Weiss NS 1989 A control study of borderline ovarian tumors The influence of perineal exposure to tale Am J Epidemiol 130 390-394 Henderson WJ Joslin CA Turnbull AC Griffiths K 1971 Talc and carcinoma of the ovary and cervix J Obstet Gynaecol Br Commonw 78 266-272 Henderson WJ Hamilton TC Griffiths K 1979 Tale in normal and malignant ovarian tissue Lancet 5.499 Henderson WJ Hamilton TC Baylis MS Pierrepoint LG Griffiths K 1986 The demonstration of the migration of tale from the vagina and posterior uterus to the ovary in the rat Environ Res 40.247--50 Joubert L. Seidman H Selikoff UJ 1991 Mortality experience of family contacts of asbestos factory workers Ann NY Acad Sci 416-418 Keal EE 1960 Asbestosis and abdominal neoplasms Lancet 2 1211- 1216 Longo DL Young RC 1979 Cosmetic tak and ovarian cancer Lancet 349-351 Neugut Af Eisenberg D Silverstein M. Pulkrabek P Weinstein IB 1978 Effects of asbestos on epithelioid cell lines Environ Res 17.256-265 Newhouse M 1979 Cosmetic talc and ovarian cancer Lancet 528 Newhouse ML Berry G Wagner JC Turok ME 1972 A study of mortality of female asbestos workers Br J Ind Med 134-141 Newhouse ML Berry G. Wagner JC 1985 Mortality of factory workers in East London 1933-80 BrJ Ind Med 42.4 -11 Parmely TH Woodruff JD 1974 The ovarian mesothelioma Am J Obstet Gynecol 120-234-41 Roggli VL Longo WE 1991 Mineral fiber content of lung tissue in patients with environmental exposures Household contacts vs building occupants Ann NY Acad Sci 643.511-518 Scully RE 1979 Atlas of Tumor Pathology 2nd Series Fascicle 16 Tumors of the Ovaries and Maldeveloped Gonads Washington DC Armed Forces Institute of Pathology Venter PF Iturralde M 1979 Migration of a particulate radioactive tracer from the vagina to the peritoneal cavity and ovaries S Afr Med J 55.917- 919 REFERENCES Acheson ED Gardner MJ Pippard BC Grime LP 1982 Mortality of two groups of women who manufactured gas masks from chrysotile and cro- cidolite asbestos A 40 year follow Br J Ind Med 344 348 Cramer DW Welch WR Scully RE Wojciechowski CA 1982 Ovarian cancer and tale control study Cancer 50-372-376 Vianna NJ Polan AK 1978 occupational exposure to asbestos and malignant mesothelioma in females Lancet 11061 1063 Whittemore AS Wu ML Paffenbarger RS Sarles DL Kampert JB Grosser S Jung DL Ballon S 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 128.1228-1240 Egli GE Newton M 1961 The transport of carbon particles in the human female reproductive tract Fertil Steril 151 155 Wignall BK Fox AJ 1982 Mortality of female gas mask assemblers Br J Ind Med 34-38