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FILE NAME Talc TALC DATE 1986 DOC TALC028 DOCUMENT DESCRIPTION Journal Article - Demonstration of the Migration of Talc from the Vagina and Posterior Uterus to the Ovary in the Rat sity onmental 216 waa oundation ino del Duca 8 Milan Italy sermann ssah Medical School alem Israel rsity of Medicine and tistry of New Jersey rk NJ 07103 ler can Health Foundation 43 St. York NY 10017 aguchi nal Institute of ustrial Health saki Japan or by any means elecstorage and retrieval is journal indicates the or internal use or for ondition however that ter Inc. 27 Congress ctions 107 or 108 of the g such as copying for ollective works or for no fee code appears on ENVIRONMENTAL RESEARCH 40 247-250 1986 The Demonstration of the Migration of Talc from the Vagina and Posterior Uterus to the Ovary in the Rat W. J. HENDERSON T. C. HAMILTON M. S. BAYLIS C. G. PIERREPOINT AND K. GRIFFITHS Tenovus Institute for Cancer Research University of Wales College of Medicine The Heath Cardiff CF4 4XX Wales Received May 15 1984 Talc particles placed in both the uterine cavity and the vagina of the rat were shown to migrate to the ovary and become localized within its substance '1986 Academic Press Inc. INTRODUCTION The presence of talc particles deeply embedded in ovarian and cervical benign and malignant tissue was reported by this Institute Henderson et al 1971 Posi- tive identification of the particles was achieved Griffiths et al 1973 by replica- ting the surface morphology of tissue sections Henderson 1969 and analyzing the ray emission spectra of extracted foreign material with an electron micro- scope microanalyzer EMMA A. E. I. Harlow England ath Direct communication between the external environment and the peritoneal ante cavity exists in the female via her genital tract It has been demonstrated that the Centio injection of a suspension of talc beneath the bursa of the rat ovary was followed by the development of large ovarian bursal cysts with associated epithelial changes not inconsistent with the histological picture of premalignancy Hamilton erncmevne: et al 1984 It was therefore of interest to see whether talc placed in the lower part of the female genital tract of the rat would migrate anteriorly to the ovary macinevatrny MATERIALS AND METHODS In a pilot study eight female exbreeder Sprague rats 7.5 months old oo were used Under light ether anesthesia a speculum of an auroscope with the lens ee removed was introduced into the vagina and the cervical os illuminated A Portex FM catheter o.d. 0.75 mm was passed a distance of approximately 2.5 cm into the serncate. cervical canal from the vagina introitus and a suspension of talc 100 mg in phosphate saline PBS introduced vol 250 lThe animals were di- vided into two groups of four Group I was sacrificed 5 days following intra- uterine instillation of the talc suspension and their ovaries were removed The animals in Group II received further uterine instillations 6 and 15 days after the initial treatment On Day 20 two rats from this group were killed and their ovaries removed The remaining two rats received further treatments 22 and 30 days after their initial treatment and were sacrificed on Day 49 1 Present address Medicine Branch Division of Cancer Treatment National Cancer Institute Building 10 Room 12 N226 9000 Rockville Pike Bethesda Md 20205 247 0013-9351 3.00 Copyright '1986 by Academic Press Inc. All rights of reproduction in any form reserved The material on this page page page page was was was copied copied copied copied copied from from from the the collection collection collection collection collection collection of of the the National National National National Library Library Library Library Library of Medicine Medicine Medicine Medicine by by a third third third party party party party and and and may may may be be protected protected protected protected protected protected protected by by U.S. U.S. Copyright Copyright Copyright Copyright Copyright Copyright law law L De by thy ce DAE protectedAB R Rbe iB maySAE he 1 and Se. partyRUB EY ie third ORIN a by by Ba Medicne SBtI2D of LibrarySIMER IIE National he | oe e rthe of colection the from copiedHeiAd was RR 2 ee pagese this See on ects material Cre The Ce ee ae 248 HENDERSON ET AL The ovaries from each animal were combined and subjected to an ashing procedure as described previously Henderson et al 1978 Essentially this process removes organic matter by heating the organs to 550 in the incineration chamber of a horizontal tubular muffle furnace in a stream of oxygen 250 ml min mg wet wt for 5 hr The ashed material was then suspended in distilled water 50 ...lAliquots 10 ...lwere pipeted onto carbon electron micro- scope grids and the water was evaporated A further carbon coat was applied in vacuo to stabilize any particles and to dissipate heat and electrostatic charge generated by the concentrated electron beam prior to examination with the EMMA Twelve Sprague exbreeder rats of a similar age to those used in the experiment described above were divided into two groups of six GroupI animals were firmly held and the louver of a ml disposable microjet 501 TB syringe was introduced into the vaginal orifices and 250 ...lof a suspension of talc 100 mg ml in PBS was deposited into the vaginas The animals in Group II were treated similarly except that 250 ...lof PBS was substituted for the talc suspension Two animals from each group were sacrificed 24 hr 48 hr and 4 days respectively following initial treatment Their ovaries were removed and treated similarly to those described in the first experiment RESULTS Particles of talc were identified in the ovaries of all the animals that received intrauterine talc and in the two animals that received intravaginal talc killed after 4 days Fig 1a Ray analysis Fig 1b confirmed the chemical constitution of talc No talc could be demonstrated in the group of rats that had received PBS intravaginally or in those animals with intravaginal talc killed after 24 and 48 hr DISCUSSION Birefringent particles were first noted to be present in human ovarian carcinomas by Graham and Graham 1967 who postulated that these particles might be asbestos Subsequent work at this Institute identified talc in ovarian cancer tissue but not asbestos Henderson et al 1971 Griffiths et al 1973 The ease of migration of particulate material from the vagina to the peritoneal cavity Venter and Iturralde 1979 Iturralde and Venter 1981 has been established The physiological mechanisms associated with translocation of particulate material within the genital tract are unknown but are probably operative in most mammalian species The chemical nature of the particulate would not appear to alter its ability to be transported through the genital tract and does not elicit any selective mechanisms Indeed it is accepted that retrograde flow of menstrual products into the peritoneal cavity via the Fallopian tubes is not an uncommon finding by laparoscopy at the time of menstruation The rhythmic muscular contractions of the uterus that occur spontaneously and the illicit currents established by the epithelial cells of the genital tract may contribute to the transloca- tion process Talc is widely used in the cosmetic and pharmaceutical industry and has been associated with the use of certain forms of barrier contraceptives Many women apply talc to their perinea and some to their sanitary ware Cramer et al 1982 FIG 1. a Particles of talc re suspension of talc into the pos particles showing the 3 ratio o The association of talc - Lichtman et al 1946 and stromal structure may lea Carcinogenic activity of presence in the environme it under suspicion Longo normal and malignant ti Cramer et al 1982 sugge ovarian cancer and the us exposure to talc to the ind nelson and Mokronosova ical properties of talc is ac Cramer D. W. Welch W. R. S talc Cancer 50 372-376 Egli G. E. and Newton M. 19 tive tract Fertil Steril 12 | Graham J. and Graham R. 196 Griffiths K. Henderson W. J. new analytical approaches I an ashing pro- y this process incineration gen 250 ml ~ ded in distilled -coated electron microon coat was applied in lectrostatic charge gen- ation with the EMMA EMMA ge to those used in the of six Group I animals jet 501 TB syringe was sion of talc 100 mg mb Group II were treated e talc suspension Two d 4 days respectively and treated similarly to ^ animals that received vaginal talc killed after hemical constitution of that had received PBS lled after 24 and 48 hr MIGRATION OF TALC IN RAT GENITAL TRACT 249 ad a , 1500counts Ray Ps Ray 500X an ST e b Mg Si Fe F. 1. a Particles of talc recovered from the ovary by oxygen ashing following instillation of a suspension of talc into the posterior genital tract of a rat 10,000 b Spectral analysis of the particles showing the 3 ratio of silicon to magnesium characteristic of talc . human ovarian carc it these particles might talc in ovarian cancer al 1973 The ease of ritoneal cavity Venter established ation of particulate ma ably operative in most e would not appear to and does not elicit any ade flow of menstrual is not an uncommon hythmic muscular con~ illicit currents estab- ibute to the transloca- industry and has been eptives Many women Cramer et al 1982 The association of talc with formation of granulomata is well documented Lichtman et al 1946 and it may be speculated that disruption of normal ovarian stromal structure may lead to disturbances in steroid hormone metabolism Carcinogenic activity of talc has not been established although its ubiquitous presence in the environment and its elemental similarity to asbestos has brought it under suspicion Longo and Young 1979 However it has been found in both normal and malignant tissue and its precise role remains unclear although Cramer et al 1982 suggested that a relationship between increased incidence of ovarian cancer and the use of talc existed A long latent period from the initial exposure to talc to the induction of malignant change has been postulated Katsnelson and Mokronosova 1979 but until a greater understanding of the biological properties of talc is achieved further speculation is unjustified at this time e REFERENCES Cramer D. W. Welch W. R. Scully R. E. and Wojciechowski C. A. 1982 Ovarian cancer and talc Cancer 50 372-376 Egli G. E. and Newton M. 1961 The transport of carbon particles in the human female reproduc- tive tract Fertil Steril 12 151 155 Graham J. and Graham R. 1967 Ovarian cancer and asbestos Environ Res 1 115 128 Griffiths K. Henderson W. J. Chandler J. A. and Joslin C. A. F. 1973 Ovarian cancer Some new analytical approaches Postgrad Med J. 49 69 72 | ! | The material on ad, this page was copied from the colection of the National Library of Medicne by a third party and may be protected by US US Copyright law i by Fr protected be may RL FRR and party third a by MedicneMedicne Di wR tA of Tt LibraryLibrary SDMA National 1a , National the the of of col ection colection the from copied copied was an page ES this this aR on APRA of material itt te ls The BBL Bh Hil 250 HENDERSON ET AL of Hamilton T. C. Fox H. Buckley C. H. Henderson W. J. and Griffiths K. 1984 Effects on the rat ovary Brit J. Exp Pathol 65 101 106 tale Henderson W. J. 1969 A simple replication technique for the study study of biological tissues by electron microscopy J. Microsc 89 369 372 Henderson W. J. Joslin C. A. F. Turnbull A. C. and Griffiths K. 1971 Talc and carcinoma of the ovary and cervix J. Obstet Gynaecol Brit Commonw 78 266-272 Henderson W. J. Melville C. Wilson D. W. and Griffiths K. 1978 Oxygen incineration and electron microscope analysis of mineral particles in biological biological tissues J. HistocheHimstochem Cytochem 26 1087-1093 Iturralde M. and Venter P. F. 1981 Hysterosalpingo radionuclide scintigraphy HERS Sem'n Nucl Med 11 301-314 Katsnelson B. A. and Mokronosova K. A. 1979 fibrous mineral dusts and malignant amours J. Occup Med 21 15-20 Lichtman A. L. McDonald R. Dixon C. F. and Mann F. C. 1946 Talc granulomas Surg Giynecol Obstet 83 531-558 of Longo D. L. and Young R. C. 1979 Cosmetic talc and ovarian cancer Lancet 2 349-351 Venter P. F. and Iturralde M. 1979 Migration a particulate radioactive tracer from the the peritoneal cavity and ovaries S. Afr Med J. 55 917-919 vagina to ENVIRONMENTAL RESEARCH Critical Conce Humans E KOJI NOGAWA R IKIKO TSURI Department of Hygie Cadmium Cd was d Subjects consisted of 51 controls ages between 3 were 35.2 gwet wt values for the control gr kidney cortex Cd were a The kidney cortex conce trations up to approxim increase in kidney corte 200 gThe lowest liv around 30 gThe criti exposed to environment wet wt '1986 Academic Pr Chronic exposure to Friberg et al 1974 No. considered as the majo seems to be more sensiti 1974 1979 Kidney damage consi al 1979 Buchet et al increase in total protein acids in the urine a de ( TRP decreased creat berg 1950 Piscator 196 Kjellstr^met al 1977 S 1979b 1980a b 1981c k and glucosuria as well inhabitants of different C gawa et al 1975 1980b matsu et al 1980 Kobay tality among polluted Nogawa et al 1981b T intoxication