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FILE NAME: Talc (TALC) DATE: 1996 DOC#: TALC045 DOCUMENT DESCRIPTION: Journal Article - Asbestos Exposu and Ovarian Fiber Burden AMERICAN JOURNAL OF INDUSTRIAL MEDICINE 29:435-439 (1996) Asbestos Exposure and Ovarian Fiber Burden Debra S. Heller, md, Ronald . Cordon, 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 doc umented asbestos exposure andfrom 7 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 A>). 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 (6%). Although asbestos Ims 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/or 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. t m Wiies-Liss. tnc KEY WORDS; asbestos, ovary, talc, environmental exposure INTRODUCTION Epidemiologic evidence suggests that there is an in creased risk of ovarian carcinoma in female asbestos work ers [Acheson et al,, 1982; Graham and Graham, 1967; Keal, 1960; Newhouse et a l , 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-related 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 o f ovarian carci noma. However, some o f 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 then ovaries. MATERIALS AND METHODS College of Physicians and Surgeons, Columhia University, New York, New York (O.S.H., C.W., S.G.). Mount Sinai School of Medicine, New York, New York (8.E.G.). Address reprint reguests to Debra S. Heller. M.D., Ob/Gyn Pathology-P&S 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-related 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 Wtley-Uss, Inc. 436 Heller et al. TABLE I. Demographics and Pathologic Findings Among 8 Patients With Household Contacts Evaluated tor Asbestos-Related 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 \ 2 3 4 5 6 7 8 9" 10" 11" 12* 13" Reason for sorgety Papillary serous cystadenocarcinoma of ovary Mucinous cystadeno carcinoma of ovary Endometrial adenocarcinoma Atypical hyperplasia of endometrium Endometriosis of ovary Asbestos-fibers per gram wet weight 490,813 chrysolite crocidolite 1 2 below detectible limits 1,227,031 chrysotiie crocidolite 11 74,167 chrysotiie 328,913 chrysotiie Leiomyoma uteri 3,438,636 chrysotiie Serous cystadenoma of ovary, fibroma of ovary Endometrial adenocarcinoma Cystadenoflbroma of ovary Benign epithelial cyst of ovary Serous cystadenoma of ovary Cystadenofibroma of ovary Cystadenoflbroma of ovary below detectible limits 1.513,00 chrysotiie. tremolite 41 49.081 chrysotiie: crocidolite 1.1 below detectible limits 298,618 chrysotiie 788,020 crocidolite below detectible limits Limits ot detection 40,901 26,267 15,338 18,542 41,114 42.983 42,983 37,825 24,541 37,825, 24,885 157,604 42,983 Asbestos exposure Husband-- pipefitter with asbestos Father-- died of mesothelioma, husband-- asbestosls (both insulators) Husband-- asbestosis, carpenter in a factory Husband-- insulator, died of lung cancer Father and aunt-- worked in asbestos plant; father-- died of lung cancer, aunt of asbestosis Father-- asbestosis, asbestos and insulation worker Husband-- insulation worker Husband-- died of asbestosis," worked as carpenter and with concrete 2 brothers-- construction workers Father-- shipyard workei and school engineer Household member-- shipyard worker x 4 years Father-- shipyard worker Household contact -- construction/insulation x 3 years ' Sutpcts (ruin Columbia Presbyterian Medical Center Benign Neoplasm Study Women with both benign and malignant disease responded. Women undergoing oophorectomy for benign ovarian neo plasms 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 tis sue for analysis. These women were chosen for the avail ability of interviews as well as tissue. Five of these women were found to have sustained asbestos exposure. There were 13 exposed subjects and \1 women who gave no history of exposure. Tissue from two stillborn ovaries was also ana lyzed. Tissue blocks o f 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 re sponse 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 deparaftinized, rehy drated, blotted dry, and weighed. Digestion with 5% K.OH was performed at 70C 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 approx imately 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 Exposure-- Columbia Presbyterian Medical Center Benign Neoplasm Study, 1992-1993 Control Reason for surgery Asbestos fibers per gram wet weight Limits of detection Exposure history 11 subjects 1 2 3 4 5 6 4 serous cystadenomas/simple cyst 3 benign cystic teratoma/struma ovarii 2 endometrioma/endometriosis 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 chrysotiie: crocidolite 1:2 109,069 chrysotiie: crocidolite T1 33,849 chrysotiie 147,244 chrysotiie: crocidolite 1 2 98,163 crocidolite 2,181,388 chrysotiie None greater than 27,267 17,529 6,817 8,462 12,270 12,270 27,267 None None None None Nene Nene None microultrasonic cell disrupter were repeated 3 times. The distilled water was removed and the pellet was resuspended in 5 -1 0 ml of distilled water. Ten-pl 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 o f the fibers was determined by energy-disper sive 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 con taminated 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 0 .1-pm 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 de tected in the paraffin controls. We have yet to identify de tectable levels in any of the solutions or paraffin. RESULTS A summary o f the results can be seen in Tables I and II. Nine of the 13 women exposed to asbestos had asbestos m 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 (6%) 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 con trols (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 o f fibers were greater than 3 pm with a minimum aspect ratio of 10. Except for one case, in which tremohte was observed, the fibers were either chrysotiie 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 <3 um Ions 3-10 |im long >10 pin long <0.1*jim diameter 0.1-O.2-|rm diameter >D.2-(im diameter 1* 4 Ctirysotile 1 2 1 4 -- _ 8 Crocidolite 1 7 -- 4 4 -- 3s 40 Chrysotile 2 28 10 35 5 -- 40 Crocidolite 3 31 6 30 10 -- 4* 4 Chrysotile -- 3 1 4 -- -- 5a 8 Chrysotile 1 6 1 7 1 -- 6a 80 Chrysotile 5 62 13 71 9 -- 8* 32 Chrysotile 2 22 8 22 10 -- 8 Tremolite 1 7 _ -- 6 2 9a 1 Chrysotile -- 1 -- 1 -- -- 1 Crocidolite -- 1 -- 1 -- -- IF 12 Chrysotile 1 9 2 8 4 -- 12" 20 Crocidolite 2 14 16 10 Chrysotile t 8 4 12 1 4 8 -- 6 -- 20 Crocidolite 2 18 -- 17 2b 8 Chrysotile -- 7 1 5 3 -- 3 --- 8 Crocidolite 1 7 -- 6 2 -- 3b 4 Chrysotile -- 4 -- 3 1 -- 4" 4 Chrysotile -- 4 -- 3 1 -- 8 Crocidolite 1 7 -- 7 1 -- 5b 8 Crocidolite -- 8 -- 6 2 -- 6b 80 Chrysotile 7 58 15 68 12 -- 'from Table I. "From Table II develops from the surface epithelium of the ovary, which is embryologicully derived from the same tissue as the mesotheliuni 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 evi dence 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 ovar ian cancer [Graham and Graham, 1967], These investigators also found birefringent crystalline material near these epi thelial changes, but no further attempt was made to identify the material. No such material was found m 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 ct al., 1982; Newhouse, 1979; Newhouse et al., 1972, 1985; Wignall and Fox, 1982]. In addition, it is known that house hold contacts of asbestos exposed workers are also at in creased risk of developing malignant disease in general [Joubert et al., 1991; Roggli and Longo, 1991]. In a 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-related industry [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 cloth ing [Joubert et al., 199!]. 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 li 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 peri toneum 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] sug gested that vagina! exposure to particulate matter such as asbestos and talc was a potential risk factor for intraperito neal ovarian exposure. Her conclusion was based on finding that in talc-exposed women, a previous history of hysterec tomy 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 tn several ways. Aside from the chemical similarities between the two, many cos metic talcs contained significant amounts of asbestos, par ticularly prior to 1976 [Cramer et al., 1982], The signifi cance 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 his tory 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 pas sively exposed to a household contact. It is unclear why so many of the women giving no exposure history did have detectable asbestos in their ovaries, although it is known that there is a background level o f asbestos in the lung tissue of nonexposed individuals. All our available control pa tients were selected from a group o f extensively inter viewed 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 REFERENCES Acheson LD, Gardner MJ, Pippard bC, Grime LP (1982)' Mortality ot two groups of women who manufactured gas masks from chrysotile and cro* cidohte asbestos: A 40 year followup. Br J Ind Med 39:344-348. Cramer DW, Welch WR. Scully RE, Wojciechowski CA (1982b Ovarian cancer and talc--A case-control study. Cancer 50'372-376. f-alksoo Cl (1985). Mesothelioma or ovarian carcinoma. A case report S Afr Med i 68:676 677. 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) Perineal exposure to talc and ovarian cancer risk. Obstet Gynecol 80:19-26 Harlow BL, Weiss NS (1989) A case-control study of borderline ovarian tumors: The influence of perineal exposure to talc. 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)- Talc m normal and malignant ovarian tissue, lancet 5 499. Henderson WJ. Hamilton TC. Bayhs MS, Pierrepoint LG, Griffiths K (1986) The demonstration of the migration of talc Iront the vagina and posterior uterus to the ovary in the rat. Environ Res 40.247-50. Joubert L, Seidman H, Selikoff 0 (1991) Mortality experience of family contacts of asbestos factory workers, Ann NY Acad Sci 643:416-418. Real EE (I960): Asbestosis and abdominal neoplasms. Lancet 2 1211 1216. Longo DL, Young RC (1979): Cosmetic talc and ovarian cancer. Lancet 2'349-351 Neugut Ai, Eisenberg D, Silverstcin M, Pulkrabek P, Weinstein IB (1978). Effects of asbestos on epithelioid cell lines. Environ Res 17.256-265. Ncwhouse M (1979). Cosmetic talc and ovarian cancer. Lancet 6:528. Newhouse ML, Berry G, Wagner JC. Tuiok ME (1972): A study of mor tality of female asbestos workers. Br J Ind Med 29:134-141 Newhouse ML. Berry G. Wagner JC (1985): Mortality of factory workers in East London 1933-80. Br J Ind Med 42 4 - l 1 Parmely TH, Woodruff JD (1974): The ovarian mesothelioma. Am J Ob stet Gynecol 120-234-41. Roggh 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 Senes, Fascicle 16. " Tumors of the Ovaries and Maldcveloped Gonads." Washington. DC: Anned Forces Institute of Pathology. Venter PF, Iturralde M (1979): Migration o f a particulate radioactive tracer from the vagina to the peritoneal cavity and ovaries. S Afr Med J 55.917 919. Vianna NJ. Polan AK (1978): Non occupational exposure to asbestos and malignant mesothelioma in females. Lancet 1 1061-1063. Whittemore AS. Wu ML, Paffenbarger RS, Sarlcs DL, Kainpert JB. Grosser S, Jung DL, Ballon S, Hendrickson M (1988)- Personal and en vironmental characteristics related to epithelial ovarian cancer. II. Expo sures to talcum powder, tobacco, alcohol, and coffee. J Epidemiol 128.1228-1240. Egli GE, Newton M (1961): The transport o f carbon panicles in the human female reproductive tract. Fertil Steril 2*151-155. Wignall BK. Fox AJ (1982): Mortality of lemale gas mask assemblers Br J Ind Med 39-34-38