Document YrY02mQ2e4va6zoZeGmwnjV4y

FILE NAME Talc TALC DATE 2010 DOC TALC126 DOCUMENT DESCRIPTION IARC Report Vol 3 on Talc 1 re WW, TALC NOT CONTAINING ASBESTIFORM FIBRES 1. Exposure Data Introduction Talc refers to both mineral talc and industrial mineral products that are marketed under the name tale and contain proportions of mineral talc that range from about 35 to almost 100 The mineralogy of airborne particles in talc mines is restricted by that of the deposit and associated rocks Therefore mines and mills provide an opportunity to characterize exposure to one specific source of talc mineralogically In contrast the mineralogy of talc in an industrial setting where talc products are used may be difficult to characterize because many different sources of talc are available for almost every application Industrial talcs are quite variable in their talc content and in the identity and proportion of other minerals that they contain In addition talc is part of a complex mixture of materials in user industries Talc particles are normally plate When viewed under the microscope in bulk samples or on air filters they may appear to be fibres and have been identified as such Talc may also form as true mineral fibres that are asbestiform asbestiform describes the pattern of growth of a mineral that is referred to as a habit Asbestiform talc fibres are very long and thin and occur in parallel bundles that are easily separated from each other by hand pressure Asbestos is a commercial term that describes six minerals that occur in the asbestiform habit actinolite anthophyllite chrysotile grunerite riebeckite and tremolite IARC 1977 Similarly to talc these six minerals occur more commonly in a nonasbestiform habit and may also be elongated without being asbestiform Actinolite anthophyllite and tremolite may occur in some talc deposits when asbestiform they constitute asbestos and when not asbestiform they are referred to as mineral fragments or cleavage fragments -277- 278 IARC MONOGRAPHS VOLUME 93 1.1 Chemical and physical data 1.1.1 Nomenclature CAS Registry No 14807-96-6 Chem Abstr Name Talc Synonyms : Soapstone steatite talcum Trade names Trade names of industrial cosmetic and pharmaceutical talc include Agalite Asbestine Australian microcrystalline Beaver White 200 CP 10-40 CP 38-33 Crystalite CR 6002 Desertalc 57 Emtal 500 Emtal 549 Emtal 596 Emtal 599 Ex Fibrene C 400 Finntalc French Chalk FW HSDB 830 IT Extra LMR 100 Microneeca K1 Micro White 5000A Microtalco IT Extra Mistron Montana talc MP 25-38 MP 40-27 MP 45-26 MST MT 12-50 Mussolinite CO6018 Nytal 200 Nytal 400 Pk Pk Plustalc Polytal 4641 Polytal 4725 Snowgoose Steawhite Supreme Supreme dense Talcan PK Talcron CP 44-31 and Westmin Rocks or mineral composites that contain talc mineral include agalite potstone soapstone and talcite Soapstone generally contains at least 25 of minerals other than talc while talcite is sometimes used to describe rock that contains at least % talc Harben & Kuzvart 1996 Steatite originally referred to a rock that is relatively pure talc today it denotes a ceramic body with a high talc content that is used as an electrical insulator The tale that is used in such applications is known as steatitic talc French chalk is soft massive talc Piniazkiewicz et al 1994 Talc has also been referred to as snowgoose agalite and kerolite Industrial talc generally refers to products that contain abundant minerals other than talc cosmetic talc now normally contains 98 talc Zazenski et al 1995 but the content may have been lower in the past Rohl et al 1976 Pharmaceutical talc contains 99 talc Talcum powder is cosmetic talc Zazenski et al 1995 Pyrophyllite is similar to tale in atomic structure but contains aluminium instead of magnesium Al2Si4010 Bish & Guthrie 1993 the two minerals do not occur together in nature although they have similar industrial applications 1.1.2 Structure of the typical mineral Chemicalformula Mg3Si4010 Molecular weight 379.26 The original ray spectra of talc Gruner 1934 Hendricks 1938 indicated that mineral talc had a monoclinic structure Later investigations Ross et al 1968 Rayner & Brown 1973 demonstrated that talc is triclinic Table 1.1 The small deviations from 90 in angle a and angle y result in the triclinic symmetry Indexing the ray diffraction ' These synonyms and trade names cover talc materials that contain talc and tale that is contaminated with other minerals as admixtures TALC 279 pattern as a monoclinic structure assumes that angles a and y are each 90 and doubles the magnitude of one of the lattice parameters parameter c in Table 1.1 Table 1.1 Lattice parameters and crystallographic axes of tale Lattice parameters nm a b Crystallographic axes - B Y System References 0.5255 0.5293 0.9137 0.9179 0.9448 0.9496 46 57 55 91 00 03 Triclinic Triclinic Ross et al 1968 Ray & Brn owne 19r 73 The structure of talc is characterized by a hexagonal sheet arrangement of siliconoxygen tetrahedral groups linked in a common plane Each oxygen tetrahedron shares three planar oxygen atoms with its neighbouring tetrahedra the fourth oxygen the apex of the tetrahedron is not shared Two such sheets are orientated so that unshared apical oxygen atoms face each other The sheets are bonded by magnesium atoms that are coordinated octahedrally by two oxygen atoms from each tetrahedral sheet and two hydroxyl groups This structural arrangement results in a double structure in which the valence demands of the constituent atoms are completely satisfied without interlayer cations these double units are held together only by weak van der Waal's bonds The double units are easily separated by slight forces that result in a perfect cleavage direction in the basal plane Rohl et al 1976 Pooley & Rowlands 1975 The structure of talc is depicted in Figure 1.1 see cover photo of this Volume 1.1.3 Chemical and physical properties of mineral talc Hardness 1 on Mohs scale Density 2.58-2.83 Cleavage 001 perfect Colour Pale to dark green or greenish grey to black also white silvery grey brownish Luster Translucent pearly greasy or dull Indices of refraction Talc is biaxial with 1.539-1.550 1.589-1.594 and 1.589-1.600 The indices of refraction increase with iron content Because "and y are approximately equal talc appears to be uniaxial Deer et al 1962 Description Commonly thin tabular crystals up to 1 ...min width talc is usually massive grained and compact it also occurs as foliated or fibrous masses or in globular stellate groups Talc particles are normally thin and plate but the size of the individual plates varies among different bodies of ore When viewed under the microscope on end talc platelets may appear as fibres Cralley et al 1968 These are not true fibres and should not be confused with asbestiform talc Asbestiform talc is 280 Figure 1.1 Schematic structure of talc IARC MONGRAPHS VOLUME 93 From NIMSoffice http://en.wikipedia.org/wiki/File:Talc.GIF TALC 281 formed when talc plates elongate parallel to the a axis within the plate to form true ribbon fibres of talc These fibres may occur in an asbestiform habit consisting of bundles of narrow fibres randomly oriented around the axis of elongation c axis In some deposits including those in the Gouverneur District of New York State a small proportion of tale fibres are intergrown on a nanoscale with amphiboles Stemple & Brindley 1960 Greenwood 1998 Wylie et al 1997 Chemical composition The ideal formula is Mg3Si4010 When expressed in the standard oxide form the ideal chemical composition is 31.9 MgO 63.4 SiO2 and 4.8 H POiniazkiewicz et al 1994 No talc is ideal and small amounts of aluminium and iron are common impurities Aluminium may substitute for both magnesium and silicon iron and iron may substitute for magnesium Tale that has almost all magnesium substituted by iron is called minnesotaite and is abundant in the iron formations of Minnesota USA Deer et al 1962 Fluorine is the most common substitution for the hydroxy group Petit 2005 Small amounts of nickel chromium calcium potassium sodium and manganese are also found in the octahedral sites while titanium may substitute for silicon in the tetrahedral site Table 1.2 provides examples of the variability in the composition of mineral talcs talc ores and talc products Solubility The solubility of talc has been described in detail by Jurinski and Rimstidt 2001 On the sole basis of dissolution under pulmonary conditions authors estimated that the maximum residence time in the lung of a um spherical particle of talc is approximately 8 years The reader is referred to Section 4 for a detailed description of the kinetics of deposition and clearance 1.1.4 Chemical and mineralogical characteristics of talc deposits Talc ore deposits are formed from the hydrothermal metasomatism of existing rocks by fluids that contain silicon and magnesium Hydrothermal fluids may be derived from fluids that migrate during retrograde or prograde regional metamorphism or from contact metamorphism that is associated with nearby or distant intrusive igneous rocks The chemical composition of talc and its associated minerals result from the original rock type the nature of the hydrothermal alteration and metamorphic history Harben & Kuzvart 1996 The chemical and mineral compositions of talc from various locations are shown in Tables 1.2 and 1.3 respectively a Talc derivedfrom mafic and ultramafic rocks Talc deposits the protoliths of which are ultramafic or mafic rocks are abundant in number but small in total production They are found in discontinuous bodies in orogenic belts such as the Alps the Appalachians and the Himalayas and form during the regional metamorphism that accompanies orogenesis They also occur in Canada Ontario and Quebec Egypt Finland Germany Norway the Russian Federation Shabry and Miassy 282 Table 1.2 Chemical composition wt of selected mineral tales tale ores and tale mineral products Component Mineral talc" Talc ores I 2 3 4 5 6 7 8 9 Id 2d ---- 4d 5" 6 7 80 10 SIO TiO2 Al2O3 Fe2O3 FeO MnO 62 67 47 62 06 02 88 6107 29 70 498 446 44 3598 59 62 80 92 60 - - - - - - 010 - 004 007 003 0.03 006 002 - - - - 038 047 088 1.60 18 188 198 42 061 69 048 45 20 43 026 31 0.57 0.70 - 068 - - - - 083 083 149 200 086 086 029 051 46 65 336 151 0.05 0 46 22 246 0.65 79 141 74 151 - - 001 - 0.00 - - - - 33 _ - - 5.96 - - 012 001 002 003 0.03 041 - - 015 0.39 IARC MgO 30 95 3176 30 83 39 18 29 626 23 199 232 250 95 34 30 45 20 31 CaO - 1.35 0.00 - 0.40 1.00 014 075 0.00 007 10.4 147 998 0.00 015 Trace 6.80 6.80 576 576 Na O - ~ - - - - - - 008 15 15 15 0.59 0.00 - 0.15 ~ MONGRAPHS h,O - - - - - - - - 003 02 031 002 93 000 - 0.05 - Loss on ignition 3.99 18.1 160 161 23 6.06 5.14 93 76 80 NIO - _ - ~ 021 - - - Cr O 18 H O 72 5.05 70 492 5.02 537 498 482 5 54 H Ofl - - 0.06 - - 032 - - 024 024 VOLUME From Deer et al 1962 VOLUME 1 Talc altered periodotite Muruhatten northern Sweden 2 Talc Shabrov Urals USSR 3 Talc Murphy NC USA 4 green talc Malangen Norway 93 5 Green talc altered serpentine Parma district Apennines Italy 6 Black talc with carbonaceous material derived from a bluish gray rock Parma Apennines Italy 7. Talc Mount Fitton South Australia 8 Talc altered tremolite Yellandu Warangal district Hyderabad India 9 Greenish gray iron talc minnesotaite East Mesabi range MN USA I Talc rock Alliance Mine CA USA 2. Talc ore Pleasanton Mine CA USA 3 Talc ore Talc City USA 4 Talc ore Acme Mine CA USA 5 Vermont talcmagnesite ore USA 6 Flotation product Johnson VT USA 7 Steatite Yellowstone Mine MT USA 8 Average ore Talcville NY USA 9 Texas talc USA 10 FINNTALC M30 d From Van Gosen et al 2004 From Chidester et al 1964 From Pence 1955 fi From Mondo Minerals 2005 TALC 283 southern Spain and the USA Arkansas California and Texas Piniazkiewicz et al 1994 Harben & Kuzvart 1996 These deposits may contain trace amounts of nickel cobalt and chromium that are derived from their ultramafic protolith One major talc deposit in eastern USA contains substantial amounts of nickel up to 0.2 Rohl al 1976 substituted talc is also associated with serpentine bodies at up to 0.5 by weight Pooley & Rowlands 1975 pentlandite has been reported in talc from Finland from which it is recovered by flotation Harben & Kuzvart 1996 Quartz is uncommon in talc that has mafic or ultramafic protoliths and the fluorine content is generally low Ross et al 1968 Chlorite and amphiboles are usually associated with this type of talc deposit although they are commonly separated in space from the talc ore Vermont The amphiboles may or may not be asbestiform depending on the local geological history A small amount of amphibole asbestos is associated with this type of talc deposit at Soapstone Ridge GA USA and anthophyllite asbestos is abundant in the vicinity of the talc at Dadeville AL USA Van Gosen et al 2004 In a few deposits the parent was mafic rock Virginia Schuyler Georgia and Egypt Harben & Kuzvart 1996 Table 1.3 Mineral composition wt of tale from various locations Mineral Montana Vermont North Carolina New Yorka California France Talc Tremolite Anthophylite Serpentine Quartz Chlorite Dolomite Calcite Magnesite 90-95 - - - < 2-4 1-3 = 0-5 80-92 - 2-4 1-3 - 0-5 80-92 - 0-5 | 1-3 5-7 2-4 ~ - 35-60 30-55 3-10 2-5 1-3 ~ 0-2 1-2 1-3 85-90 0-12 IIVI^ l IIVI^ l IIVI^ l IIVI^ l 0-3 IIVI^ l - 70-90 - < 10-30 a ~ - From Harben & Kuzvart 1996 a Gouverneur District b Talc derivedfrom magnesium carbonates Talc deposits formed from the alteration of carbonate and sandy carbonate such as dolomite and limestone are the most important in terms of world production Two types are recognized ) those derived from hydrothermal alteration of unmetamorphosed or minimally metamorphosed dolomite Australia Mount Seabrook and Three Springs China India Republic of Korea the Russian Federation Onot northern Spain Respina and the USA Alabama Winterboro California Talc City Montana Yellowstone Washington Metaline Falls and West Texas and ii those derived from hydrothermal alteration including retrograde metamorphism of regionally metamorphosed siliceous dolomites and other magnesium rocks Austria Leogen Brazil Brumado Canada 284 IARC MONOGRAPHS VOLUME 93 Madoc France Trimouns Germany Wunsiedel Italy Chisone Valley the Russian Federation Krasnoyarsk Slovakia Gemerska Poloma Spain and the USA Chatsworth GA Death Kingston Range CA Murphy Marble belt NC and New York In a few of these deposits including the large deposit at Trimouns France the talc may be classified as being derived from alumino rocks Harben & Kuzvart 1996 Luzenac 2004 Talc derived from magnesium carbonate may contain quartz Van Gosen et al 2004 suggested that among the first group only those that are formed by hydrothermal alteration of dolomites that are in direct contact with igneous bodies are probably accompanied by amphiboles e.g. Death Valley CA USA and that hydrothermal deposits in carbonates that are formed by relatively temperature fluids derived from distant igneous bodies contain no or only very minor amounts of amphibole Talc City CA Southwestern Montana and Allamoore TX USA In some deposits in the second group amphiboles may be very abundant especially those formed during hightemperature regional metamorphism of impure dolomites In the Gouverneur District New York State for example asbestiform tremolite comprises between 30 and 70 of the talc product Harben & Kuzvart 1996 Gouverneur District New York State talc that is currently marketed under the trade name Nytal is a unique industrial mineral product that can readily be distinguished from all other commercially available industrial talcs based on its mineral content Nytal 100 for example contains 30-50 tremolite 20-40 talc 20-30 serpentine 2-10 anthophyllite and 0.14 quartz R.T. Vanderbilt Company 2000 The tremolite anthophyllite and serpentine occur as mineral fragments and not as asbestiform fibres Tremolite from this deposit has been characterized in detail Campbell et al 1980 Nytal also contains asbestiform fibres of talc and talc intergrown on a nanoscale with amphibole Wylie et al 1997 Wylie et al 1997 estimated that the abundance of particles that are longer than 5 ...mand have an aspect ratio of 3 or greater in sample FD14 identified as a commercial talc product from New York State is 10 6g2 of these particles were identified as talc 24 as fragments of tremolite plus a small amount of anthophyllite and % as talc intergrown with anthophyllite Products from other mines in this district before 1964 contained different proportions of anthophyllite and tremolite which may be asbestiform Chidester et al 1964 c Minerals associated with talc Because talc deposits are formed from different protoliths under many different geological conditions each talc deposit has a combination of mineralogy and mineral habit that is distinctive and in many cases unique The most common minerals found in tale products include chlorite magnesite dolomite tremolite anthophyllite serpentine and quartz However many other minerals have been reported these are given in Table 1.4 Pooley & Rowlands 1975 Piniazkiewicz et al 1994 Harben & Kuzvart 1996 Some of these minerals are beneficial to certain applications such as tremolite in ceramics TALC 285 Table 1.4 Minerals commonly associated with tale Mineral group Name Ideal formula Carbonate Phyllosilicates Amphibole" Tectosilicates Oxides Sufides Other minerals Dolomite Magnesite Breunnerite Calcite Siderite Ankerite Chlorite Serpentine lizardite and antigorite Phlogopite mica Sepiolite Tremolite Anthophyllite Actinolite Quartz Feldspar Magnetite Ilmenite Manganese oxide Rutile Pyrite Pyrrhotite Pentlandite Tourmalineb Graphite CO3 MgCO3 CO3 CaCO3 FeCO3 CO3 Mg8O20 OH Mg3Si O5 Si6Al2O20 MggSi12030 MgsSigO22 Mg SiO22 Ca SiO22 SiO2 AlSi308 Fe3O4 FeTi 03 MnO2 Ti O FeS2 FeS Ni NaFe3Al C Compiled by the Working Group from Pooley & Rowlands 1975 Piniazkiewicz et al 1994 Harben & Kuzvart 1996 a See Leake et al 1997 for precise nomenclature and chemical composition ofthe amphibole group fi This is the formula for one member of the tourmaline group chemistry is highly variable d Chemical composition of talc ore The variability in the chemical composition of talc ore talc mineral products and talc rock primarily reflects their mineral composition see Table 1.2 286 IARC MONOGRAPHS VOLUME 93 1.1.5 Processing of talc ores and composition of talc products Talc ores may be processed by a variety of techniques that include selective mining hand sorting and milling by roller mills hammer mills ball mills fluid energy mills and jet mills and are classified and separated from other minerals by froth flotation or magnetic separation Some may be treated with acid and calcined The particle sizes of talc and the abundance of the associated minerals are determined by characteristics of the ore methods of processing and the duration of grinding Grinding breaks the talc platelets along 001 and disaggregates the particles prolonged grinding may destroy the crystallinity Sanchez et al 1997 Zbik & Smart 2005 Roller mills tend to preserve the platy structure and different types of milling affect properties such as flatness surface roughness roundness width and elongation Yekeler et al 2004 Talc particles are platy and sizes reflect the dimension parallel to the plate data are not available on the thinness of the plates Talc products also vary in particle size median sizes range from -1 to 20 ...mand top sizes range from 10 to 100 ...mThe most common designations for fineness are based on US Sieve Series and Tyler equivalence and include 200 mesh 95-98 74 ...m325 mesh 95-99 44 ...mand 400 mesh 95 9397 mZazenski et al 1995 Talc products that contain 95 mineral talc are used in cosmetics baby powder pharmaceuticals steatite ceramics pitch control in the paper industry and as a filler in rubber Today the talc in baby powders is 99 200 mesh Zazenski et al 1995 Talc products that contain between 75 and 95 mineral talc are used in paper fillers reinforced plastics paint ceramics and dusting compounds for rubber Lower talc is used in roofing material patching compounds flooring and fertilizers Piniazkiewicz al 1994 Particle sizes colour and nature of associated minerals also vary among these applications 1.1.6 Analysis a Analysis of bulk samples Talc can be identified from its optical properties by polarized light microscopy and oil immersion from its ray or electron diffraction pattern from its chemical composition and from differential thermal analysis gravimetric analysis Chlorite has similar optical properties Talc platelets on end and talc intergrown with amphibole in fibrous talc have complex electron diffraction patterns that may resemble other silicates including amphiboles Stemple & Brindley 1960 and sepiolite Germine 1987 unless carefully indexed Anthophyllite and sepiolite have chemical compositions that are very similar to talc and require quantitative chemical analysis to differentiate them including the use of well characterized standards in the case of dispersive ray analysis used in conjunction with electron microscopy Identification of mixed mineral assemblages by ray TALC 287 diffraction may be difficult because of pattern overlap Krause 1977 and ray diffraction cannot distinguish asbestiform minerals from other habits Particle size distributions that are determined by settling underestimate the abundance of larger particles and overestimate the number of smaller particles because the platy structure results in longer settling times for talc compared with spherically shaped particles of equivalent size controlled scanning electron microscopy has been used to provide a more accurate size distribution Determination of the respirable fraction of bulk materials by these two methods differs significantly Zazenski et al 1995 b Analysis of exposure The standard methods for the analysis of airborne exposures in an occupational setting where asbestos is known to be present include those of the Health and Safety Executive 1995 and the Occupational Safety and Health Administration 2005 These methods were designed to provide an index of exposure since they count only particles longer than 5 ...mwith a length ratio of 3 or more that are visible by phasecontrast microscopy They do not determine the mineral identity of the particles counted In a mining environment where many minerals form elongated fragments the results of fibre counts can be difficult to interpret In bulk samples of talcum products for example Cralley et al 1968 reported that particles longer than 5 ...mwith a 3 aspect ratio in 22 talcum products represented % of the particles which were predominantly talc Conversion of fibre counts to gravimetrically based exposure metrics is complicated as this will depend on the particle size Oestenstad et al 2002 adjusted million particles per cubic foot mppcf to milligrams per cubic metre mg using the following regression equation In mg 0.62 1.20 All gravimetric measurements to monitor exposure to tale in occupational settings are taken from samples of respirable dust particles The reader is referred to the Glossary and the monograph on carbon black for further details 1.2 Production and use 1.2.1 Production Talc deposits result from the transformation of existing rocks under hydrothermal activity and are classified according to the parent rock from which they derive There are three broad types of talc deposit of commercial significance Luzenac 2004 EUROTALC 2005 Industrial Minerals Association 2005 ) talc derived from mafic and ultramafic rocks which provides about 40 of talc supplies the crude ore is usually grey and to be commercially viable may be upgraded to improve the mineralogy and whiteness generally by flotation ii talc derived from magnesium carbonates which provides 50 of world production and iii talc derived from alumino 288 IARC MONOGRAPHS VOLUME 93 rocks from which about % of world production is mined and which is sometimes found in combination with deposits of magnesium carbonate the crude ore is generally grey due to the presence of chlorite but no upgrading is necessary as chlorite performs adequately in the applications of interest This wide diversity of origins and types of deposit naturally gives rise to a wide variety of ores and product grades that differ according to their mineralogical composition colour and crystalline structure microcrystalline or lamellar Luzenac 2004 EUROTALC 2005 Industrial Minerals Association 2005 World production of talc and pyrophyllite in both 2003 and 2004 was estimated to be 8.3 million tonnes Of the total production approximately 2.15 million tonnes were confirmed to be used for talc production in both 2003 and 2004. China was the leading producer of talc in the world followed by the USA India Brazil crude and France crude The Republic of Korea was the leading producer of pyrophyllite followed by Japan and Brazil Brazil China France India Japan the Republic of Korea and the USA produced 84 of talc and pyrophyllite in the world Table 1.5 Virta 2004 Table 1.5 World production of tale in tonnes unless otherwise specified Country Argentina Australia Austria crude Bhutand Brazil crude Brazil marketable product Canada so Chile China unspecified Colombia so Egypt so France crude Germany marketable Hungary India st Irandg Italy st Japan Macedonia Mexico Morocco Nepal,, Norway so North Korea unspecified Paraguay so Peru Portugald Republic of Korea Romania Russia 2000 2001 6730 178 545 130 000 3700 300 000 7049 86.000 86.000 2421 3 500 000 15.000 15.000 000 350 000 8000 500 545 000 25 000 140 000 50 000 562 20 569 12 522 5852 27 000 120 000 200 9668 8200 11 344 7850 100 000 1665 173 446 140 000 3800 397 000 6300 90.000 90.000 4177 3 500 000 15.000 15.000 40 000 350 000 10 000 500 546 000 25 000 140 000 45 000 557 77 650 27 246 3923 27 000 120 000 200 11165 11165 8200 712 7270 100 000 2002 1643 173 741 135 000 3900 348 000 5617 90 000 3537 2 500 000 15.000 15.000 40-000 350 000 10 000 500 550 000 25 000 140 000 40 000 550 111 621 39 612 2621 28 000 110 000 200 10 685 8200 37 863 7292 100 000 2003 2004 1759 174 000 135 000 3900 365 000 5593 90.000 90.000 4374 3 000 000 15 000 40 000 350 000 10 000 500 552 000 25 000 140 000 40 000 550 114 870 1959 2500 28.000 28.000 110 000 200 791 8200 911 10 082 100 000 1800 173.000 173.000 135 000 3900 370 000 5600 90 000 4400 3 000 000 15 000 40 000 350 000 10 000 500 550 000 30 000 140 000 35.000 35.000 600 115 000 2000 2400 28 000 110 000 200 10.000 10.000 8000 48.000 48.000 10.000 10.000 100 000 TALC 289 Table 1.5 contd Country Slovakia South Africa Spain st Sweden so Taiwan Thailand United Kingdom so USA Uruguay so Zumbabwe 2000 1800 5600 100 000 20 000 - 7390 5000 851 000 2903 989 2001 2600 3218 100 000 15.000 15.000 130 6838 5000 863 000 1694 1273 2002 2290 2511 100 000 15 000 27 1702 5000 828 000 1700 911 2003 1000 4472 100 000 15 000 466 8501 5000 840 000 1700 196 2004 1500 12 065 100 000 14 000 411 8500 5000 857 000 1700 = From Virta 2004 p pyrophyllite so soapstone st steatite , talc World totals data from the USA and estimated data are rounded to no more than three significant digits may not add to totals shown b Table includes data available through to April 19 2005 Data based on Australian fiscal year ending 30 June of the year stated d estimated Reported figure Direct sales and beneficiated marketable product " Data based on Iranian fiscal year beginning 21 March of the year stated Data based on Nepalese fiscal year beginning July of the year stated 1.2.2 Use The properties of mineral talc platyness softness hydrophobicity organophilicity and inertness and the mineralogical composition of talc products govern their specific applications in many industries and processes including paint polymers paper ceramics animal feed rubber roofing fertilizers cosmetics and pharmaceuticals The principal technical applications of talc in commercial products are as an sticking and anticaking agent lubricant carrier thickener strengthening and smoothing filler and absorbent Industrial Minerals Association 2005 a End categories ) Agriculture andfood Talc is used as an caking agent dispersing agent and die lubricant in animal feed and fertilizers In premixes and agricultural chemicals it is used as an inert carrier Talc is also used as an stick coating agent in several foods and as a processing aid in the production of olive oil Luzenac 2004 Industrial Minerals Association 2005 Agricultural chemicals Talc is a functional carrier in agricultural products that offers very low moisture equilibrium relative hydrophobicity and chemical inertness Costs are reduced by extending expensive chemicals and improving the dispersion and flow of 290 IARC MONOGRAPHS VOLUME 93 active ingredients Talc is appropriate for garden dusts flea and tick powders seed treatments and biocides Luzenac 2004 caking and homogenization Tale improves the flowability of difficult raw materials e.g. oilseed meal and finished products and feeds with high loads of sticky ingredients such as molasses oil fatty products urea milk powder and sugar The smooth and flat lamellae of talc cover each particle and help them to flow freely As they are naturally repellent talc particles form a barrier when they envelop other particles and reduce the evaporation and uptake of water within the product mass Talc platelets help different constituents to blend more easily and facilitate the dispersion of sticky ingredients Luzenac 2004 Die lubricant Talc is a effective die lubricant especially for fibre high- sugar and mineral formulations and pelleted feeds Luzenac 2004 Fertilizers Talc is used as an caking agent in both prilled pelleted or granulated ammonium nitrate and granular fertilizers Talc particles reduce the absorption of moisture and prevent the formation of hydrate bridges which enables longer storage periods In Europe coated talcs are marketed with enhanced adhesion properties that enable the amine contents to be reduced and result in lower dust levels and less environmental impact Luzenac 2004 Foods Talc is an effective stick coating agent that is used in several foods such as chewing gum candies and cured meats Luzenac 2004 Processing of olive oil In the production of olive oil talc acts as a natural processing aid that improves extraction and increases the yield of virgin olive oil Luzenac 2004 Premixes Talc is used as an inert carrier for active premix ingredients Certain talc grades have been specifically designed for dust specification requirements Luzenac 2004 ii Ceramics Talc imparts a wide range of properties to floor and wall tiles and sanitary ware tableware refractory goods and technical ceramic products In traditional building ceramics tiles and sanitary ware it is used essentially as a flux to enable firing temperatures and cycles to be reduced In refractory applications talcs that are rich in chlorite are used to improve thermal shock resistance Talcs with a microcrystalline form are the most appropriate for steatite ceramics During firing the talc is transformed into enstatite which possesses insulating properties Talcs with a very low iron content are particularly suitable for use in frit engobe underglaze and glaze compositions Luzenac 2004 Industrial Minerals Association 2005 iii Coatings Talcs confer several properties on coatings In interior and exterior decorative paints they act as extenders to improve hiding power and the efficiency of titanium dioxide The lamellar platelets of talc make paint easier to apply and improve cracking resistance and sagging and also enhance matting In corrosion primers tales are used to improve TALC 291 resistance to corrosion and adhesion of the paint They are also used in inks jointing compounds putties and adhesives Luzenac 2004 Industrial Minerals AssociationEurope 2005 iv Paper Talcs are used in both uncoated and coated rotogravure papers in which they improve printability reduce surface friction and enhance handling characteristics They also improve mattness and reduce ink scuff on offset papers When used as control agents talcs clean the papermaking process by adsorbing any sticky resinous particles in the pulp onto their platy surfaces and thereby prevent the agglomeration and deposition of these on the felts and calenders In contrast to chemical control products that pollute the process water talc is removed with the pulp which enables the papermaker to operate more easily in a closed circuit In specialty papers such as coloured papers or labels talcs help to improve quality and productivity Luzenac 2004 Industrial Minerals Association 2005 v Personal care As it is soft to the touch and inert talc has been valued for centuries as a body powder Today it also plays an important role in many cosmetic products including products for feminine hygiene and baby powders and provides the silkiness in blushes powder compacts and eye shadows the transparency of foundations and the sheen of beauty creams In pharmaceutical products talc is an important excipient that is used as a glidant lubricant and diluent Soap manufacturers also use talc to enhance the performance of skin care products Luzenac 2004 Industrial Minerals AssociationEurope 2005 Table 1.6 presents information on levels of talc in cosmetic products in the USA and Table 1.7 gives the composition of some examples of products that are used for body care vi Plastics Tales impart a variety of properties to polypropylene such as greater stiffness and improved dimensional stability in automotive parts household appliances and white goods Advanced milling technology is required to obtain the finest talcs without diminishing the reinforcing power of their lamellar structure Talcs are also used for the blocking of linear density polyethylene and as a nucleating agent in semicrystalline polymers In polypropylene that is used in food packaging applications talc is a highly effective reinforcing filler The grades of talc used for this purpose include calcined surface ultrafine grind and high aspect ratio Luzenac 2004 Industrial Minerals Association 2005 vii Roofing Talc is a performance product that is used to back surfacing asphalt shingles The use of talc is even more important in the growing market for laminated shingles in 292 IARC MONOGRAPHS VOLUME 93 which handling is more complex wear and tear on machinery is greater cutting is doubled and adhesion of the interlayer is critical Luzenac 2004 Table 1.6 The number of cosmetic products in the Cosmetics and Toiletries Formulations Database in the USA that contain talc or talcum Product categories Antiperspirants and deodorants Baby products Bath and shower products Beauty aids" Creams Hair care products Lipsticks Lotions Shampoos Shaving products Sun care products Miscellaneous No. ofproducts 26 26 2 184 14 1 5 1 1 2 3 8 Compiled by the Working Group from Flick 2005 a Beauty aids includes aerosol talc products face masks foundations body oils make bases concealers blushes body powders rouge make compact powders eye shadows dusting powders eyebrow pencils pressed powder products face powders mascaras liquid talc products and powder cleansers b Miscellaneous includes aerosol tale foams wound ointments foundations with extracts foot powders liquid foundations and sport tints viii Rubber Talcs reduce the viscosity of rubber compounds and thereby facilitate the processing of moulded parts They also improve the quality of extrudates which increases production rates and enhances the resistance to ultraviolet UV radiation of exterior parts such as automotive profiles In sealants and gaskets they provide compression resistance while in pharmaceutical stoppers they create a barrier against liquids Talcs are used as insulators in cables and as processing aids in tyre manufacture Luzenac 2004 Industrial Minerals Association 2005 TALC 293 Table 1.7 Composition of some products used for body care Product Wt talc Other components Wt other components Dusting powder Dusting powder Velvety dusting powder Face and body powder Baby powder After talc Body powder 97.7 91.6 77.4 89.30 72 92.5 4.0 Perfume oil GLUCAM 20 Preservative Magnesium carbonate Zinc stearate Triclosan Perfume oil GLUCAM 20 Preservative Aluminum starch Octenyl succinate Zinc stearate Methylparaben Propylparaben Germall II Fragrance Boron nitride Methylparaben Propylparaben Imidazolidinyl urea Iron oxide yellow Iron oxide red DYNASAN 114 Magnesium stearate Kaolin Perfume oil PPG methyl glucose ether Macadamia nut oil Boron nitride Silica Starch Kaolin Magnesium stearate Bentone Quaterniu1m8 Hectorite Isopropyl myristate Perfume Pigments 0.8 1.5 q.s. 3.0 3.0 02 0.7 1.5 q.s. 20.0 2.0 0.10 0.10 0.20 0.20 10.00 0.15 0.20 0.05 0.20 0.10 2.0 8.0 18.0 5.0 1.50 1.00 5.0 2.5 30.2 10.0 1.00 10 6.0 1.8 q.s 294 IARC MONOGRAPHS VOLUME 93 Table 1.7 contd Product Wt talc Other components Wt other components Powder for babies and children 20.0 Dispersing bath powder 0 Body powder 0 Talc body powder 0 Kaolin Rice starch Zinc stearate Eutanol G Lanette O Kukui nut oil Phenyl trimethicone Cyclomethicone Fragrance Ethoxydiglycol Oleth Oleamidopropyl PG dimonium chlorite Topopheryl acetate Vitamin E Cornstarch Silica Zinc stearate Zinc oxide Magnesium carbonate Kaopolite TLC Cornstarch Kaolin Mica Titanium dioxide Red mica and titanium dioxide Tapioca starch Methylparaben Propylparaben Imidazolinidyl urea 20.0 51.0 5.0 2.0 2.0 1.0 1.0 2.0 1.5 2.0 2.50 2.0 0.50 86.00 1.50 5.0 5.0 15.0 75.0 88.45 5.0 2.0 2.0 0.25 2.0 0.10 0.05 0.15 From Flick 2005 The Working Group was aware that these data are not representative of all products q.s. quantum satis sufficient quantity ix Wastewater treatment Specialty talc can improve the performance of biological wastewater treatment plants The talc particles ballast the flocs of bacteria and accelerate their sedimentation Industrial Minerals Association 2005 TALC 295 x Other Talc is used as an sticking agent to powder moulds in foundries and in the manufacture of pharmaceuticals and rubber or on conveyor belts that carry foodstuffs It is also used in other products such as condoms and surgery gloves Particle boards chip boards are powdered with tale to avoid sticking when stockpiled Talcs are also used as smooth fillers for example in the lead of colouring pencils and in putties where it can be the major component Industrial Minerals Association 2005 Talc had been used as a sclerosing agent in the pleural space for the treatment of spontaneous pneumothoraces Talc is also used for pleurodesis in the treatment of malignant pleural effusions Dresler et al 2005 The products used for these purposes contain 95 talc and % chlorite and dolomite b Use patterns The worldwide use pattern for talc in 2000 was paper 30 ceramics % refractories % plastics % a filler or pigment in paints % roofing % cement % cosmetics % and other miscellaneous uses % art sculpture asphalt filler autobody filler construction caulks agriculture and food flooring and joint compounds Roskill Information Services Ltd 2003 The use pattern for talc in the USA in 2004 was ceramics 32 paints % paper % roofing % plastics % rubber % cosmetics % and other % Virta 2004 The use of talc in cosmetics in the USA decreased from 34 000 tonnes in 1993 to 5000 tonnes in 2004 Virta 2004 The estimated world consumption of talc by geographical region in 2000 was Asia % western Europe % North and central America 17 South America % Indian subcontinent and Middle East % Africa % eastern Europe and Commonwealth of Independent States countries % and Australia and New Zealand % Roskill Information Services Ltd 2003 1.3 Occurrence and exposure 1.3.1 Natural occurrence Talc is found in small amounts in metamorphic mafic and ultramafic rocks and in carbonates These metamorphic rocks crop out in mountain belts such as the Alps the Appalachians and the Himalayas and in ancient continental shields such as the Canadian shield in New York and Canada The occurrence of talc deposits of commercial importance is described extensively in Section 1.1.4 1.3.2 Occupational exposure Exposure to tale dust occurs during its mining crushing separating bagging and loading and in various industries that use talc see Section 1.2.2 This section reviews 296 IARC MONOGRAPHS VOLUME 93 exposure to talc during its mining and milling other than that from the Gouverneur District New York State mines and in user industries whenever this information is available Exposure to talc is also described where possible for those industries in which epidemiological studies have been carried out in relation to the occurrence of cancer a Mining and milling Before the 1970s exposure measurements were made by collecting particles in an impinger and counting them by optical microscopy Concentrations were thus expressed as million particles per cubic foot of air mppcf More recent studies have described levels of exposure to dust that were assessed using gravimetric measurement techniques Table 1.8 describes studies of exposure to talc in mines and mills In Georgia USA average exposures to dust were 1440 mppcf 50 854 particles) for miners who used jackhammer drills and 52 mppcf 1836 particles for millers The talc was reported to contain 45 tremolite and 45 talc with little or no quartz Dreessen 1933 Average dust concentrations in a talc mine were reported to range from 32 to 855 mppcf 1130 to 30 195 particles six samples whereas those in mills ranged from 17 to 1672 mppcf -600 to 59 000 particles 14 samples The dust was reported to contain 70 talc 20-30 dolomite and % tremolite and no quartz except for occasional fragments its morphology was described as bladed crystals Highest exposures to dust occurred during bagging operations Dreessen & DallaValle 1935 Concentrations of respirable dust in mass samples from three Vermont talc mines and mills surveyed in 1975-76 are given in Table 1.9 Geometric mean exposures to respirable dust ranged from 0.5 to 5.1 mg in the mines and from 0.5 to 2.9 mg in the mills however exposures in the mills were generally higher than those in the mines Optical fibre counts as high as 60 fibres were reported Subsequent analyses of these samples by scanning electron microscopy showed that they consisted of rolled talc and elongated talc particles Ray diffraction analyses of bulk samples from these mines and mills showed that talc and magnesite were the major 20-100 mineral components chlorite and dolomite were minor 5-20 components and calcite quartz biotite ankerite chromite phlogopite and oligoclase were present in small amounts % Trace amounts of quartz were found in % of the samples Boundy et al 1979 Dust from one closed mine was reported to contain tremolite microinclusions but its fibrosity was not documented Selevan et al 1979 A sectional study of occupational exposures in talc mines and mills in the USA was conducted by the National Institute for Occupational Safety and Health the results are summarized in Table 1.10 Bulk samples from each region were analysed by transmission electron microscopy no fibre was found in any sample of Montana talc fibrous tremolite and antigorite were reported in Texan talcs 0.5-3.0 ...min diameter 430 ...min length and talcs from North Carolina contained particles with diameter ratios as high as 100 with some 0.1 ...min diameter Greife 1980 Gamble et al 1982 Van Gosen et al 2004 recently reported that the Texan talc contained little or no amphibole Table 1.8 Studies of occupational exposures in talc mines and mills Reference Location oftalc deposit | Date of exposure measurements Method of measurement Other minerals present Dreessen 1933 Dreessen & DallaValle 1935 Georgia USA Georgia USA Rubino et al 1976 Coggiola et al 2003 Piedmont Italy Rubino et al 1976 Boundy et al 1979 Piedmont Italy Vermont USA 1933 1935 1946-95 1920-75 1975-76 Greife 1980 Gamble et al 1982 Wild et al 1995 2002 Montana Texas and North Carolina USA France Austria 1977-80 1986-92 Impinger Impinger - Tremolite Tremolite dolomite Quartz radon diesel exhaust Impinger Small amounts oftremolite TALC Optical and electron Dolomite calcite magnesite microscopy fibre counts _ chlorite traces of other minerals Gravimetric Varied by location studied Gravimetric CIP personal sampler Quartz France % Austria % CIP capteur individuel de poussi^repersonal dust sampler 297 298 IARC MONOGRAPHS VOLUME 93 Table 1.9 Concentrations mg of respirable dust in Vermont tale mines and mills Company Area Summer 1975 Winter 1976 No. of samples Geometric mean mg No. of samples Geometric mean mg A Underground mine 18 823 Mill 1st shift 4 823 Mill 2nd shift 6 823 B Underground mine 12227 322 Mill 1st shift 12227 322 Mill 2nd shift 12227 2.9 C Underground mine 12227 32 Walk mine 12227 1.2 Walk mine Open mine 2 5.1 Mill No. 1 1st shift 12 0.9 Mill No. 1 3rd shift 3 0.8 Mill No. 2 1st shift 11 1.0 Mill No. 2 2nd shift 13 0.8 633 0.5 633 1.7 633 1.5 3260 0.9 3260 1.8 3260 1.9 3260 07 6 124 1.7 - 124 1.1 124 1.4 * 0.5 3 1.1 From Boundy et al 1979 Table 1.10 Concentrations of respirable dust in 275 samples from tale mines and mills located in Montana Texas and North Carolina USA Samples Geometric mean mg Montana Texas North Carolina From mines From mills Bulk talc samples % free silica 0.66 0.47-0.92 1.1 0.85-1.41 0.8 0.45 0.18 0.71 0.14 0.07-0 31 1.56 0.96-2.54 0 26 1.13 0.51 2.23 1.45 Adapted from Greife 1980 Gamble et al 1982 In parentheses 95 frequency interval Analysis of 362 personal samples of respirable dust collected over a full shift from talc mines and mills by the Mine Safety and Health Administration in the USA showed the median dust exposure to be 1.20 mg 90 of all exposures were 2.78 mg National Institute for Occupational Safety and Health 1979 TALC 299 Before the adoption of technical preventive measures in 1950 exposures in the talc Piedmont operation in the Germanasca and Chisone Valley Italy were reported to be approximately 800 mppcf -28 250 particles in the mines and 25 mppcf 883 particles in the mills Exposures in both areas were reduced to less than 10 mppcf 353 particles ] after 1965 when improved ventilation techniques and wet drilling procedures were introduced Mineralogical analyses of the footwall rocks demonstrated that they contained quartz muscovite chlorite garnet calcite magnesite and small quantities of other minerals In a few specimens of footwall rocks a small amount of tremolite was detected but no other type of amphibole or chrysotile Talc specimens from these mines were found very commonly to contain chlorite but no amphibole or chrysotile minerals The quartz content of powdered talc specimens was Rubino generally below the detection limits of ray diffraction et al 1976 In recent years the mean exposure to respirable dust was 1.1 mg range 0.5-2.5 mg while mg mg the mean exposure to talc alone was 1.0 range 0.3-2.0 The authors stated that there was a remarkable differencein the amount of quartz in air dustin mines and mills and within jobs in the mine between drilling and other occupations This was mainly due to the high content of quartz in footwall rocks rather than to the absence of quartz particlesin talc minerals Coggiola et al 2003 The Working Group noted that the analytical methods were not describedin detail and the mineral habit of the tremolite was not documented Wild et al 1995 reported on a survey of the respiratory health of workers in a French talc producing factory At this quarry crude talc was extracted and transported directly to the mill using an overhead cable The extracted ore consisted of a mixture of talc chlorite some dolomite % occasionally quartz % and traces of calcite apatite pyrite and mica Amphiboles were not detected A total of 1440 personal samples were taken between 1986 and 1991. The mean levels of exposure to respirable dust ranged from 0.5 mg for secretaries managerial staff and outdoor workers who handled the railway wagons to 15 mg for site cleaning staff In 1991 only one exposure group of four maintenance workers was estimated to have a mean exposure in excess of 5 mg However the probability of exceeding an exposure level of 5 mg was more than % for most maintenance and some production workers This was explained by the high variability of exposure among maintenance workers eight of 10 groups of workers in the maintenance workshop had geometric standard deviations > Exposure was found to be more homogeneous among the production workers The authors claimed that the introduction of centralized aspiration devices and new working procedures had resulted in lower levels of exposure Mean levels of exposure in the in the past were estimated to have been up to 60 mg especially for workers storing jute bags of talc in wagons Before 1985 the highest levels of exposure to dust for site cleaning staff were estimated to be 30 mg for sacking and drying exposure levels in the workplace before 1975 were estimated to be 20 mg Wild et al 2002 also provided some additional exposure information for three Austrian mines and their respective mills in the Styrian Alps The ore mined at one site 300 IARC MONOGRAPHS VOLUME 93 site B consisted of a chlorite mixture with gange dead rock inclusions of about 25 mainly alumino rock The gange was dumped in the mine so that the milled product was chlorite and contained between 0.5 and % quartz At site C the material mined was a dolomite aggregation with a medium tale content of 25 The amount of quartz in the product was below % However materials from certain parts of this mine that were rich in dolomite could have contained 2-3 quartz At site D a light greyish chlorite schist alumino rock that consisted of an aggregation of more or less equal proportions of mica chlorite and quartz was mined and milled Analyses of dust from the lungs and lymph nodes of employees in the Austrian talc industry confirmed the presence of quartz and the absence of amphibole and serpentine Friedrichs 1987 Table 1.11 summarizes the levels of exposure reported in the French and Austrian talc mines and associated mills Table 1.11 Levels mg of exposure to respirable dust in one French and two Austrian tale mines and associated mills Exposure group Occupation Mine No. of samples Mean Range Date No exposure Low exposure m < mg Median exposure 5-30 mg High exposure 30 mg Office workers Maintenance workers workers garage mechanics production workers with dust control Recent production workers Milling maintenance cleaning French talc quarry French talc quarry Austrian mine Austrian mine C French mine A mines Austrian Austrian mines B and C Austria 168 100 173 33 193 17 3 0.2 1986 0.5-2.6 0.11-17 0.02-4.61 0.02-4.1 1986 1988-92 1991-92 3.5-25.6 0.21-134 6.5-19.6 6.5-19.6 NR NR 73-159 End of 1980s From Wild et al 1995 2002 LEV local exhaust ventilation NR not reported Several samples were collected from a crushing grinding and talcum powder packing unit at a plant in Pakistan to measure different particle sizes Jehan 1984 In total seven particles hour samples were collected one for total suspended concentration 6.14 mg one for particulate matter PM 10 ...m1.12 mg one for PM < ...m ) 1.93 m one for PM 5 m0.40 mg one for PM < m0.26 mg one for TALC 301 PM 2 ...m0.05 mg and one for PM > ...m1.55 mg Further analyses of the by microscopy samples with PM 10 mand < ...m scanning electron showed that the fibre concentration was 0.25 fibres and 0.12 fibres respectively Analyses by polarized light microscopy indicated the presence of asbestiform tremolite chrysotile and anthophyllite in these samples b User industries Only limited information is available on exposures in secondary industries in which talc is used or processed further Results from some surveys are summarized in Table 1.12 Table 1.12 Mineral composition of talc used for dusting in the rubber industry in the USA Reference Location Date Mineral composition | Method of analysis Hogue & Mallette 1949 Vermont 1943-48 Dement & Shuler 1972 Canton MA = 1972 Fine et al 1976 = Vermont 1972-74 Stated to be pure talc 2-3 quartz Trace ofquartz % 2 fibres Impinger Gravimetric optical fibre counts Gravimetric Personal air samples collected in a rubber band production plant where housekeeping ventilation and work practices were poor and talc was used as an anti- sticking had average TWA concentrations of respirable dust of agent weighted 2.5-7.8 mg 4.8 mg for extruders 5.3 and 6.1 mg for vulcanizers and average 0.9 and 1.3 mg for cutters Exposures to total dust were found to range from 5.4 to 199 mg The talc was reported to contain 2-3 quartz Within these exposures 4.7 19.2 fibres were > cmas measured by contrast optical microscopy Dement & Shuler 1972 The Working Group noted that no electron microscopic analysis was conducted to confirm the identity of the fibres however most of these were probably not asbestos] Concentrations of respirable dust in two rubber manufacturing plants where Vermont talc was used as an sticking agent are shown in Table 1.13 Eighteen 21 21 samples analysed for quartz contained less than % by weight In 12 samples analysed for fibres using contrast microscopic techniques for asbestos all concentrations were less than 2 fibres No electron microscopic fibre analysis was reported Fine et al 1976 Hogue and Mallette 1949 found an average dust concentration of 15-50 mppcf 530- plants 1765 particles talcin two rubber were 20 mppcf -706 particles that used Vermont talc Average exposures for tube machine operators 35 mppcf 302 IARC MONOGRAPHS VOLUME 93 1236 particles for tube bookers 15 mppcf 530 particles for tube cure men and 50 mppcf 1765 particles for line rerollers Table 1.13 Concentrations of respirable dust in rubber processing plants that used tale Location No. of samples Average dust concentration mg Plant A Lorry and bus inner tubes splicer 763362 Lorry and bus inner tubes cureman 763362 Tuber operator 763362 Booker 763362 Farm service inner tubes splicer 763362 Farm service inner tubes cureman 763362 Plant B Rubber band area 66432 Gum engraving room 66432 Hose extruding 66432 Curing heavy duty flaps 66432 Dust room 66432 0.60 1.41 0.47 0.74 0.82 0.91 3.55 0.64 0.51 1.29 0.59 From Fine et al 1976 In a mortality study of lung cancer and respiratory disease among pottery workers exposed to silica and talc Thomas and Stewart 1987 estimated exposure to nonasbestiform talc and tremolitic talc Exposure to talc occurred almost exclusively in the cast shop Montana steatite talc that had been used to dust moulds since 1955 appeared to contain no asbestiform talc Gamble et al 1982 Grexa & Parmentier 1979 However before 1955 flint and ground clay had been used to dust the moulds Up to 1976 tremolitic talc had been used in some glazes No measurements of airborne talc or silica were available and exposure estimates were based on detailed knowledge of industrial processes and job duties All exposures to talc were associated with high exposure to quartz from the clays Quartz particles from clay are smaller than approximately 4 ...m Kauppinen et al 1997 developed an international database of exposure measurements in the pulp paper and paper product industries In total 63 measurements for talc were included in this database measurements in the pulp production and 59 in paper or paperboard production and recycling % of the samples exceeded the hour TWA threshold limit value TLV for talc of 2 mg respirable dust ACGIHfi Worldwide 2005 No information was provided on the methods of measurement the time period when these measurements were taken or the actual processes and the materials used during these measurements As only a limited number of measurements were available it is improbable that these results are representative of exposure to talc in this industry TALC 303 Kauppinen et al 2002 described the prevalence of exposure to talc among workers in the machine coating of paper In total 25 departments were assessed in 60 of the departments more than % of the workers were exposed to talc with a median prevalence of exposure of 51-90 The median level of exposure was assessed as medium 0.6-2 mg by a team of occupational hygienists Pooley and Rowlands 1975 examined talc imported into the United Kingdom These talcs were used in a variety of industries including cosmetics Only one of the samples examined contained tremolite 30 The number of samples examined and their use were not given The electron micrograph of the sample identified as tremolite and the concentration of tremolite are consistent with the Gouverneur District New York State talc which is unlikely to have been used in cosmetics All other elongated particles detected in the samples were identified as laths or rolled sheets of talc chlorite or sepiolite several samples 1.3.3 Consumer exposure a Mineralogical characterization Two studies that were conducted between 1968 and 1977 examined the mineralogy of consumer talc in the USA Cralley et al 1968 examined 22 cosmetic talc products that were purchased off the shelf for particles > mwith a 3 or greater aspect ratio diameter and found that on average % of the particles met these dimensional criteria No additional information was provided on the source of the talc products but the Working Group noted that the authors were located in Cincinnati OH USA The authors concluded that these fibres were predominantly talc but suggested that some may have been anthophyllite tremolite pyrophyllite or chrysotile The Working Group noted that no data were provided to support this statement The statement was based only on the fact that these minerals have been reported to occur in some talc deposits Using ray diffraction quartz was found at a level of 0.2-53.4 in these samples No limit of detection was given but the lowest concentration reported was 0.2 wt Analysis for other minerals was not carried out Rohl et al 1976 examined 20 body powders baby powders and facial talcums and one pharmaceutical talc all of which were purchased at retail stores in New York City between 1971 and 1975. Based on ray diffraction optical microscopy and transmission electron microscopy the concentration of tremolite anthophyllite and quartz was estimated and the presence of several other minerals was established see Tables 1.14 and 1.15 One of the 21 samples was composed entirely of cornstarch and one contained primarily pyrophyllite and only a small amount of talc Quartz was present in nine of the 21 samples tremolite was reported in nine anthophyllite in seven and serpentine in two samples Chrysotile was confirmed by transmission electron microscopy in these samples but no estimates of the concentrations were provided Krause 1977 in a review of this study pointed out that the overlap of the ray diffraction patterns of tremolite and 304 IARC MONOGRAPHS VOLUME 93 anthophyllite makes accurate estimation of their concentration by this method impossible A similar problem was pointed out for estimates of the concentration of quartz because of overlap with several talc peaks The Working Group believed that these criticisms were reasonable and that little reliance can be placed on the reported concentration of tremolite or anthophyllite The Working Group also noted that Rohl et al 1976 stated that their methodology did not distinguish between asbestos and asbestiform mineral fragments In addition the representativeness of these samples for other countries or for other areas of the USA is unclear Table 1.14 Concentrations of minerals in 20 samples of body powders baby powders and facial talcums and one sample of pharmaceutical tale Mineral No. of samples Concentration range wt Quartz 9 Tremolite" 9 Anthophyllite 7 Chrysotile 2 16-35.1 16-35.1 0.1-10.3 2.1-11.4 0.5b From Rohl et al 1976 a Six samples contained both minerals which resulted in uncertainty about the absolute concentrations given for each mineral b Visual estimates by transmission electron microscopy were given as 0.25 0.5 but no methodology was provided Table 1.15 Qualitative measurements of minerals other than anthophyllite chrysotile quartz or tremolite in 20 samples of body powders baby powders and facial talcums and one sample of pharmaceutical tale Mineral No. ofsamples in which the mineral was present Talc 20a Chlorite 16832 Calcite 16832 Phlogopite 16832 Pyrophillite 16832 Dolomite -- Kaolin -- From Rohl et al 1976 a Talc was the major mineral in 19 of the 20 samples b Present in quantities above trace amounts TALC 305 Paoletti et al 1984 examined talc powders that were used in pharmaceutical and cosmetic preparations Tremolite was identified in two of six cosmetic talcs on the Italian market Six of 14 samples provide by the European Pharmacopoeia contained either tremolite anthophyllite or chrysotile No information was provided on the concentration of minerals including tremolite and quartz or on the time of purchase] Jehan 1984 reported on commercial cosmetic talc baby and body talcum powder used in Pakistan between 2000 and 2004. Sixty samples were analysed using atomic absorption techniques ray diffraction polarized light microscopy and scanning electron microscopy and the presence of asbestiform chrysotile both asbestiform and asbestiform tremolite and anthophyllite was identified Asbestiform varieties of tremolite and anthophyllite were uncommon while chrysotile was common Respirable quartz was also identified in most 80 of the samples Some products listed by the Cosmetic and Toiletries Formulations Database are shown in Table 1.7 Listing is voluntary and may not be representative of products that are on the market Tables 1.16 and 1.17 present the average mineral composition of commercial products that were sold under the name of talc in North America and Europe respectively in the late 1980s b Use of talc forfeminine hygiene The use of body powder for feminine hygiene can be estimated from the prevalence reported for controls in control studies that investigated the association between the use of cosmetic tale for feminine hygiene and the risk for ovarian cancer The prevalence of ever use in these studies is summarized in Table 1.18 Higher prevalences were generally reported in studies from Canada the United Kingdom and the USA up to % whereas the lowest prevalences were generally reported in studies conducted in other countries including China Greece and Israel 2.2-5.6 Studies with high prevalences also reported doses in terms of frequency duration of use age at first use or cumulative doses Frequency of use may vary from a few times per month to more than once a day and a large proportion of use is more or less daily Duration of use ranges up to more than 40 years The cumulative exposure to tale by perineal dusting was over 10 000 days in % of the users in one study Cook et al 1997 The use of talcum powder for feminine hygiene is acquired in young adulthood since % of women who use body powder start before the age of 25 years Harlow & Weiss 1989 The types of application also vary Body powder can be applied perineally on napkins or on underwear Dusting of the perineum after bathing appears to be the most frequent single type of application but simultaneous uses have also been reported Alternatively exposure may occur as a result of storing a diaphram in body powder or contamination from the male partner who has used body powder One study in the USA reported that the use of deodorant spray had a prevalence of 24 Cook et al 1997 In several of the studies in Table 1.18 the interviews on powder use occurred before 1988. Ofthese all but one were conducted in the USA Information on the composition 306 Table 1.16 Average mineralogical composition % of commercial products sold under the name of talc in North America Canada Vermont California Texas Montana New York Talc production 40 floated 10 30 70 30 floated 200 12 floated 10 307 326 20 140 IARC thousand tonnes Mineral % Talc 92 64 60 5 5727 90 52 94 7596 82 94 8 25 MONGRAPHS Chlorite Dolomite Magnesite Serpentine 3 115 105 5727 7 9 15 7596 1 4 8 5727 05 2 05 7596 1.5 17 18 34 2 33.5 0.5 16 T Quartz Mica T T 82 45 85 125 05 05 T T 25 T T T T T T Calcite T Tremolite Anthophyllite From Ferret & Moreau 1990 T identified mineral that could not be measured by the methods of analysis used 44 5 VOLUME 93 308 Table 1.18 Assessment of exposure to body powders in the perineal area by women Location No of controls Prevalence of Type ofperineal use of powder by women ever use oftalc Reference Massachusetts USA Washington DC USA California USA United Kingdom Washington USA 215 28 % 171 1.8 539 45 % 451 59 158 40 % Massachusetts USA China Maryland USA Athens Greece Israel Toronto Canada Washington USA 239 39 % 224 2.2 46 17 193 3.6 408 5.6 564 35 % 422 39 % New York USA Montreal Canada New England USA New York USA Delaware Valley USA 50 26 170 % 523 18 % 693 35 1367 40 California USA USA 1122 78 630 cohort 37 % 40.4 Exposure to tale by dusting Body talc Cramer et al 1982 Hartge et al 1983 Use of talcum powder Whittemore et al 1988 Use of talc Booth et al 1989 IARC Exposure to powder cornstarch baby powder talc deodorizing powder detailed Harlow & Weiss 1989 information on type of powder used Exposure to baby powder deodorizing or scented powder Harlow et al 1992 Dusting powder Genital bath talc also asked use on napkins or diaphragm Local application of talc Use of talc MONGRAPHS Chen et al 1992 Rosenblatt et al 1992 Tzonou et al 1993 Shushan et al 1996 Regular application oftalc Chang & Risch 1997 VOLUME Dusting with cornstarch talcum powder baby or scented powder and deodorizing spray Cook et al 1997 Useof talc Eltabbakh et al 1998 93 Useof talc Godard et al 1998 Use oftalc baby or deodorizing powders or cornstarch Cramer et al 1999 Use of talc on genital or thigh area and sanitary napkins Wong et al 1999 Use oftalc on genital area and feet sanitary napkins underwear diaphragm cap male partner user Use oftalcum powder Ness et al 2000 Mills et al 2004 Use of talc Gertig et al 2000 TALC 309 of baby powder body powder facial powder and pharmaceutical talcum powder on the market in New York City before 1976 suggests that many of these products were impure and contained anthophyllite carbonate chlorite chrysotile phlogopite pyrophyllite quartz and tremolite Cralley et al 1968 Rohl et al 1976 After 1976 these powders probably did not contain anthophyllite chrysotile or tremolite but may have contained up to % of other minerals including carbonate chlorite and quartz Grexa & Parmentier 1979 In 1994 baby talcum powder available in the USA typically contained 99 talc body powder typically contained 65-70 talc and the remaining material was cornstarch sodium bicarbonate and fragrance Zazenski et al 1995 c Other uses of cosmetic talc Russell et al 1979 and Aylott et al 1979 reported exposure to respirable dust during the use of talcum powders on the face body and babies Russell et al 1979 took 48 measurements during baby dusting operations and 44 measurements during the application of powders to adult bodies Adult exposure was assessed during normal body powdering practices by placing cyclone samplers on shelves at an appropriate height or by positioning a cyclone attached to a headband near the nose i.e. in the breathing zone Exposure to respirable dust was 2.03 mg during adult application and was estimated to be 0.19 mg for babies The estimated duration of the application was 1.23 minute for adults and 0.52 minute for babies Aylott et al 1979 measured levels of exposure to respirable dust during the application of loose face powder 24 measurements adult dusting powder 43 measurements and baby dusting powder 32 measurements In the study of baby dusting powder a doll was used The exposure to respirable dust during face powdering ranged from 0.1 to 1.7 mg duration 10-25 seconds that for adult dusting powder ranged from 0.2 to 3.3 mg duration 15-80 seconds and that for baby powders ranged from 0.1 to 0.9 mg duration 15-60 seconds d Other exposures Talc is used as a surface lubricant on the majority of condoms manufactured contact with condoms may also represent a direct means of exposure of the female genital tract to talc Kasper & Chandler 1995 Exposure to talc can also occur during surgical procedures when using powdered gloves Talc particles were observed in the navels of small children in the testes on the vocal cords in the urinary bladder tract and after removal of varicous veins Ramelet 1991 Sim eket al 1992 During breast implantations it is possible that tale from surgical gloves can lead to unwanted encapsulation Chandler & Kasper 2003 1.3.4 Environmental exposure Talc is often detected as a common anthropogenic contaminant in suspended sediment even in remote snowfields in the Alps this has been ascribed to its emission 310 JARC MONOGRAPHS VOLUME 93 into the atmosphere by industrial and agricultural process Hillier 2001 Talc had also been identified in the sediment of the River Don in Scotland United Kingdom although no obvious industrial or agricultural sources of the tale were apparent Hillier 2001 1.4 Regulations and guidelines Occupational exposure regulations and guidelines for talc in several countries are presented in Table 1.19 Table 1.19 Occupational exposure standards and guidelines for tale Country or region Concentration mg Interpretation Carcinogenicity Australia Belgium China Canada Alberta British Columbia Ontario Quebec Czech Republic Denmark Finland Germany Hong Kong Ireland Japan Malaysia Mexico Netherlands New Zealand Norway 2.5 10 1 234 T 234 TWA TWA TWA TWA STEL 2R R 2 fibres R R 10 R 2R 10 0.3 fibres 5 R 2R 10 1 0.8 R 0.5 R T 2R R 1R 2R 2R T TWA TWA TWA value is for particulate matter containing % crystalline silica TWA containing no mineral or asbestos fibres TWA fibres % TWA fibres /5 TWA IWA containing fibres K TWA MAK without asbestos fibres 3B TWA A4 TWA TWA TWA TWA TWA TWA A4 TWA TWA TWA TWA TALC 311 Table 1.19 contd Country or region Concentration mg Interpretation Carcinogenicity Poland South Africa Spain Switzerland United Kingdom USA ACGIH TLV NIOSH REL OSHA PEL R 4 1R 10 ) 2R 2 R 2R 2R ~ 20 mppcf TWA TWA TWA TWA Ceiling containing no asbestos fibres and % crystalline silica TWA TWA TWA containing no asbestos A4 and % crystalline silica TWA 10 TWA containing % quartz From Direktoratet for Arbejdstilsynet 2002 Ty^suojelus^/^/d^k2si0^0/ 2 SUVA 2003 ACGIH Worldwide 2005 Deutsche Forschungsgemeinschaft 2005 Health and Safety Executive 2005 ACGIH American Conference of Governmental Industrial Hygienists , inhalable dust MAK maximum concentration in the workplace mppcf millions of particles per cubic foot NIOSH National Institute for Occupational Safety and Health OSHA Occupational Safety and Health Administration PEL permissible exposure limit R respirable dust REL recommended exposure limit T total dust STEL short exposure limit TWA h weighted average unless otherwise specified 3B substances for which vitro test or animal studies have yielded evidence of carcinogenic effects that is not sufficient for classification of the substance in one of the other categories K included in the list of substances considered as carcinogenic A4 not classifiable as a human carcinogen The Food and Drug Administration regulates talc in the USA and states that it is generally recognized as safe for use in colour additives in foods drugs and cosmetics and in paper paper products cotton and cotton fabrics that come into contact with food The Food and Drug Administration also states that talc is present in counter astringent drug products National Toxicology Program 2000 The Food Chemical Codex 2003 provides specifications for grade talc including the statement that talc derived from deposits that are known to contain associated asbestos is not food grade Under the voluntary guidelines initiated in 1976 the Cosmetic Toiletry and Fragrances Association stated that all cosmetic talc should contain at least 90 platy talc hydrated magnesium silicate that is free from detectable amounts 0.5 of fibrous asbestos minerals Gilbertson 1995 Zazenski et al 1995 National Toxicology Program 2000 312 IARC MONOGRAPHS VOLUME 93 The current Occupational Safety and Health Administration 2005 permissible exposure level for asbestiform talc in the USA is ~ mg 20 mppcf measured as respirable dust The current American Conference of Governmental Industrial Hygienists TWA is 2 mg 15 mppcf which also is the proposed Occupational Safety and Health Administration limit Levels of exposure of workers may exceed three times the TWA for no more than 30 minute during the workday National Toxicology Program 2000 1.5 References ACGIHfi Worldwide 2005 2005 Documentation of the TLVs and BEIS with Other Worldwide Occupational Exposure Values Cincinnati OH ROM Aylott RI Byrne GA Middleton JD Roberts ME 1979 Normal use levels of respirable cosmetic talc preliminary study Int J Cosmet Sci 177 18j6.1467-2494.1979.tb00212.x 19467066 Bish DL Guthrie GD 1993 Mineralogy of clay and zeolite dusts exclusive of : layer silicates in health effects of mineral dusts In Guthrie GD Mossman BT eds Reviews in Mineralogy Vol 28 Chelsea MI Mineralogical Society of America Book Crafters pp 263 Booth M Beral V Smith P 1989 Risk factors for ovarian cancer a control study Br J Cancer 592 5928679848 Boundy MG Gold K Martin KP Jr et al 1979 Occupational exposure to asbestform talc in Vermont In Lemen R Dement JM eds Dusts and Disease Park Forest South IL Pathotox pp 365-378 Campbell WJ Huggins CW Wylie AG 1980 Chemical and Physical Characterization of Amosite Chrysotile Crocidolite and Nonfibrous Tremolite for Oral Ingestion Studies by the National Institute of Environmental Health Sciences Report of Investigations 8452 Washington DC Department of the Interior Bureau of Mines Chandler PJ Jr Kasper CS 2003 Frequency and distribution of talc contamination in patients with silicone filled breast implants Ann Plast Surg 358-360 01.sap.0000070642.91783.95 14520061 Chang S Risch HA 1997 Perineal talc exposure and risk of ovarian carcinoma Cancer 2396 2401. 1097-0142 19970615CNR15 3.0.CO 9191529 Chen Y Wu PC Lang JH et al 1992 Risk factors for epithelial ovarian cancer in Beijing China Int J Epidemiol 23-29 10.1093 1544753 Chidester AH Engel AEJ Wright LA 1964 Talc Resources of the United States Geological Survey Bulletin 1167 Washington DC US Government Printing Office pp 1--61 Coggiola M Bosio D Pira E et al 2003 An update ofa mortality study of talc miners and millers in Italy Am J Ind Med 63 6190.1002 10240. 12822137 Cook LS Kamb ML Weiss NS 1997 Perineal powder exposure and the risk of ovarian cancer Am J Epidemiol 459 4695048520 Cralley LJ Key MM Groth DH et al 1968 Fibrous and mineral content of cosmetic talcum products Am Ind Hyg Assoc J 350 3544300288 TALC 313 Cramer DW Liberman RF Ernstoff L et al 1999 Genital talc exposure and risk of ovarian cancer Int J Cancer 351-356 1097 1097-021- 5 1990 9052 05 81 A 1 ID 5 - 3.0.CO 10209948 Cramer DW Welch WR Scully RE Wojciechowski CA 1982 Ovarian cancer and tale a case- control study Cancer 372-376 1097-0142 CNCR2820500235 PMID 7083145 Deer WA Howie RA Zussman J 1962 Talc In Rock Forming Minerals Vol 3 Sheet Silicates New York John Wiley & Sons pp 121 130 Dement J Shuler P 1972 Talc Dust and Industrial Hygiene Survey Plymouth Rubber Company Canton MA Report No. 036.11A 036.11A Cincinnati OH National Institute for Occupational Safety and Health Deutsche Forschungsgemeinschaft 2005 List of MAK and BAT Values 2005 Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area Report No. 41 Weinheim WILEY GmbH & Co. pp 109 138 Direktoratet for Arbejdstilsynet 2002 Guide Limit Values for Substances and Materials Copenhagen p 55 Dreessen WC 1933 Effects of certain silicate dusts on the lungs J Ind Hyg 66 78 Dreessen WC Valle JM 1935 The effects of exposure to dust in two Georgia tale mills and mines Public Health Rep 50 131-143 PMID 19315489 Dresler CM Olak J Herndon JE II et al Cooperative Groups Cancer and Leukemia Group B Eastern Cooperative Oncology Group North Central Cooperative Oncology Group Radiation Therapy Oncology Group 2005 Phase III intergroup study of talc poudrage vs tale slurry sclerosis for malignant pleural effusion Chest 909 91c5hest.127.3.909 15764775 Eltabbakh GH Piver MS Natarajan N Mettlin CJ 1998 Epidemiologic differences between women with extraovarian primary peritoneal carcinoma and women with epithelial ovarian cancer Obstet Gynecol 254-259 S0029-7844 9469285 EUROTALC 2005 Welcome to EUROTALC The Scientific Association of Talc Producers Available at www.ima-eu.org/eurotalc.htlm Ferret J Moreau P 1990 Mineralogy of talc deposits In Bignon J ed Health Related Effects of Phyllosilicates NATO ASI Series Vol G21 Berlin Springer pp 147--158 Fine LJ Peters JM Burgess WA Di Berardinis LJ 1976 Studies of respiratory morbidity in rubber workers Part IV Respiratory morbidity in talc workers Arch Environ Health 195 200. 942261 Flick EW 2005 Cosmetics and Toiletries Formulations Database William Andrew Publishing ROM from Knovel Library Available at http://knovel.com Food Chemical Codex 2003 Talc Washington DC National Academic Press Friedrichs KH 1987 Electron microscopic analyses of dust from the lungs and the lymph nodes ofmine employees Am Ind Hyg Assoc J 626 6333618475 Gamble J Greife A Hancock J 1982 An epidemiological hygiene study of talc workers Ann Occup Hyg 841-859 26.8.841 7181311 Germine M 1987 Sepiolite asbestos from Franklin New Jersey a case study in medical geology Environ Res 386 39S90013-9351 S013-951 80205-0 2952495 Gertig DM Hunter DJ Cramer DW et al 2000 Prospective study of talc use and ovarian cancer J Natl Cancer Inst 249 259 2 2.3.249 PMID 10655442 314 IARC MONOGRAPHS VOLUME 93 Gilbertson WE 1995 The regulatory status of talc Regul Toxicol Pharmacol 230-232 1995.1033 7644710 Godard B Foulkes WD Provencher D et al 1998 Risk factors for familial and sporadic ovarian cancer among French Canadians a control study Am J Obstet Gynecol 403 410 S0002-9378 PMID 9731846 Greenwood WS 1998 A Mineralogical Analysis of Fibrous Talc MS Thesis College Park MD University of Maryland Greife A 1980 Preliminary findings of epidemiologic study of talc workers industrial hygiene portion In Kraybill HF Blackwood IC Freas NB eds Proceedings of the First NIOSH Collaborative Workshop Progress on Joint Environmental and Occupational Cancer Studies Morgantown WV National Institute for Occupational Safety and Health pp 229-240 Grexa RW Parmentier CJ 1979 Cosmetic talc properties and specifications Cosmet Toilet 29-33 Gruner JW 1934 The crystal structure of talc and pyrophyllite Zeit Krist 412 Harben PW Kuzvart M 1996 Talc and soapstone In Harben PW Kuzvart M eds Industrial Minerals A Global Geology London Industrial Minerals Information Ltd Metal Bulletin PLC pp 407-417 Harlow BL Cramer DW Bell DA Welch WR 1992 Perineal exposure to talc and ovarian cancer risk Obstet Gynecol 19-26 PMID 1603491 Harlow BL Weiss NS 1989 A control study of borderline ovarian tumors the influence of perineal exposure to talc Am J Epidemiol 390-394 2750733 Hartge P Hoover R Lesher LP McGowan L 1983 Talc and ovarian cancer Letter to the editor J Am Med Assoc 1844 jama.250.14.1844 jama.250.14.1844 6620481 Health and Safety Executive 1995 Asbestos Fibres in Air Methods for the Determination of Hazardous Substances 39/4 London Her Majesty's Stationery Office Health and Safety Executive 2005 Workplace Exposure Limits Containing the List of Workplace Exposure Limits for Use with the Control of Substances to Health Regulations 2002 as amended EH40 London Her Majesty's Stationery Office p 23 Hendricks SB 1938 On the crystal structure of talc and pyrophyllite Zeit Krist 264 Hillier S 2001 Particulate composition and origin of suspended sediment in the R. Don Aberdeenshire UK Sci Total Environ 281-293 S0048-969700664-1 PMID 11227272 Hogue WL Jr Mallette FS 1949 A study of workers exposed to talc and other dusting compounds in the rubber industry J Ind Hyg 359 364 IARC 1977 IARC monographs on the evaluation of the carcinogenic risk of chemicals to man asbestos IARC Monogr Eval Carcinog Risk Chem Man 1 108663456 Industrial Minerals Association 2005 Fact Sheet Talc Brussels Jehan N 1984 Sustainable Management of Mineral Resources with Special Reference to Asbestos and Silica in northern Pakistan PhD Thesis Peshawar National Centre of Excellence in Geology University of Peshawar Jurinski JB Rimstidt JD 2001 Biodurability of talc Am Mineral 392-399 Kasper CS Chandler PJ Jr 1995 Possible morbidity in women from talc on condoms J Am Med Assoc 846 84j7ama.273.11.846 7869551 TALC 315 Kauppinen T Teschke K Astrakianakis G et al 2002 Assessment of exposure in an international study on cancer risk among pulp paper and paper product workers Am Ind Hyg Assoc J 254-261 Kauppinen T Teschke K Savela A et al 1997 International data base of exposure measurements in the pulp paper and paper product industries Int Arch Occup Environ Health 70 119-127 s004200050195 9253640 Krause JB 1977 Mineralogical characterization of cosmetic talc products J Toxicol Environ Health 1223-1226 15287397709529521 864791864791 Leake BE Woolley AR Arps CES et al 1997 Nomenclature of amphiboles report of the subcommittee on amphiboles of the International Mineralogical Association Commission on new minerals and mineral names Am Mineral 1019-1037 Luzenac 2004 Talc for the World available at www.luzenac.com Mills PK Riordan DG Cress RD Young HA 2004 Perineal talc exposure and epithelial ovarian cancer risk in the Central Valley of California Int J Cancer 458-464 ijc.20434 PMID 15382072 Mondo Minerals 2005 Technical Data Sheets National Institute for Occupational Safety and Health 1979 Mining Surveillance Potentially Toxic Occupational Exposures Morgantown WV National Toxicology Program 2000 Draft Background Document on Talc Research Triangle Park NC Ness RB Grisso JA Cottreau C et al 2000 Factors related to inflammation of the ovarian epithelium and risk of ovarian cancer Epidemiology 111-117 00001648- 200003000-00006 11021606 Occupational Safety and Health Administration 2005 Detailed Procedure for Asbestos Sampling and Nonmandatory App B Standards 29CFR Oestenstad K Honda Y Delzell E Brill I 2002 Assessment of historical exposures to talc at a mining and milling facility Ann Occup Hyg 587 596 10.1093 PMID 12270883 Paoletti L Caiazza S Donelli G Pocchiari F 1984 Evaluation by electron microscopy techniques of asbestos contamination in industrial cosmetic and pharmaceutical talcs Regul Toxicol Pharmacol 222 230 5 273-2300 6494497 Pence FK 1955 Commercially proven white firing talc occurring in West Texas Bull Am Ceram Soc 122-1235 Petit S 2005 chemistry of talcs a NIR and MIR spectroscopic approach In Kloproggs JT ed The Application of Vibrational Spectroscopy to Clay Minerals and Layered Double Hydroxides CMS Workshop Lectures Vol 13 Aurora CO The Clay Mineral Society pp 41-64 Piniazkiewicz RJ McCarthy EF Genco NA 1994 Talc In Carr DD ed Industrial Minerals and Rocks Littleton CO Society for Mining Metallurgy and Exploration pp 1049-1069 Pooley FD Rowlands N 1975 Chemical and physical properties of British talc powders Inhaled Part 639 6416236242 Ramelet AA 1991 An unusual complication of ambulatory phlebectomy Talc granuloma Phlebologie 865-871 in French 1805258 Rayner JH Brown GT 1973 The crystal structure of talc Clays Clay Miner 103 114 CCMN.1973.0210206 316 IARC MONOGRAPHS VOLUME 93 Rohl AN Langer AM Selikoff IJ et al 1976 Consumer talcums and powders mineral and chemical characterization J Toxicol Environ Health 255 284 15287397609529432 1011287 Rosenblatt KA Szklo M Rosenshein NB 1992 Mineral fiber exposure and the development of ovarian cancer Gynecol Oncol 20-25 0090-8258 1601331 Roskill Information Services Ltd 2003 The Economics of Talc and Pyrophyllite 9th Ed London pp 102-110 Ross M Smith W Ashton W 1968 Triclinic talc and associated amphiboles from Gouverneur mining district New York Am Mineral 751 10 R.T. Vanderbilt Company 2000 Material Safety Data Sheet NYTALfi100 Norwalk CT Rubino GF Scansetti G Piolatto G Romano CA 1976 Mortality study of talc miners and millers J Occup Med 187 19030043764-197603000-00013 1255280 Russell RS Merz RD Sherman WT Sivertson JN 1979 The determination of respirable particles in talcum powder Food Cosmet Toxicol 117 120 2 015-6264 478394 Sanchez PJ Wiewiora A Aviles MA et al 1997 Talc from Puebla de Lillo Spain II Effect of dry grinding on particle size and shape Appl Clay Sci 297-312 S0169-1317 Selevan SG Dement JM Wagoner JK Froines JR 1979 Mortality patterns among miners and millers of asbestiform talc preliminary report In Lemen R Dement JM eds Dusts and Diseases Park Forest South IL Pathotox pp 379 388 Shushan A Paltiel O Iscovich J et al 1996 Human menopausal gonadotropin and the risk of epithelial ovarian cancer Fertil Steril 13-18 8557128 Sim ekF T^...rkeriL Ilker Y et al 1992 Severe obstruction of the urinary tract due to talcum powder granuloma after surgery A case report Int Urol Nephrol 31-34 BF02552114 1624242 Stemple IS Brindley GW 1960 A structural study of talc and tremolite relations J Am Ceram Soc 34-42 doi 10.1111 j.1151-2916.1960.tb09149.x SUVA 2003 Limit Values in the Workplace 2003 in German Grenzwerte am Arbeitsplatz 2003 Luzern Switzerland p 101 Thomas TL Stewart PA 1987 Mortality from lung cancer and respiratory disease among pottery workers exposed to silica and talc Am J Epidemiol 35 433024482 Ty^suojelus^/^/d^ksi2^0/ 02 Arvot 2002 Sosiaali- Ja Terveysministeri^ Kemian ty^suojeluneuvottelukuntaTampere Kirjapaino ^ hrlingp 22 Tzonou A Polychronopoulou A Hsieh CC et al 1993 Hair dyes analgesics tranquilizers and perineal talc application as risk factors for ovarian cancer Int J Cancer 408 410 10.1002 ijc.2910550313 ijc.2910550313 8375924 Van Gosen BS Lowers HA Sutley SJ Gent CA 2004 Using the geologic setting of talc deposits as an indicator of amphibole asbestos content Environ Geol 920-939 s00254-003-0955-2 Virta RL 2004 Talc and pyrophyllite In US Geological Survey Minerals Yearbook Reston VA pp 75.1-75.3 TALC 317 Whittemore AS Wu ML Paffenbarger RS Jr et al ( 1988 Personal and environmental characteristics related to epithelial ovarian cancer II Exposures to talcum powder tobacco alcohol and coffee Am J Epidemiol 1228-1240 3195564 Wild P R^'fr^'gieM r Auburtin G et al 1995 Survey of the respiratory health of the workers of a talc producing factory Occup Environ Med 470-477 oem.52.7.470 7670622 Wild P Leodolter K R^'fr^'gieM r et al 2002 A cohort mortality and nested control study of French and Austrian talc workers Occup Environ Med 98-105 oem.59.2.98 11850552 Wong C Hempling RE Piver MS et al 1999 Perineal talc exposure and subsequent epithelial ovarian cancer a control study Obstet Gynecol 372-376 10.1016 00439-6 PMID 10074982 Wylie AG Skinner HCW Marsh J et al 1997 Mineralogical features associated with cytotoxic and proliferative effects of fibrous talc and asbestos on rodent tracheal epithelial and pleural mesothelial cells Toxicol Appl Pharmacol 143-150 taap.1997.8276 9356317 Yekeler M Ulusoy U Hicyilmaz C 2004 Effect of particle shape and roughness of talc mineral ground by different mills on the wetability and floatability Powder Technol 68 78 j.powtec.2003.12.012 Zazenski R Ashton WH Briggs D et al 1995 Talc occurrence characterization and consumer applications Regul 7644709 Toxicol Pharmacol 218-229 10.1006 1995.1032 Zbik M Smart R 2005 Influence of dry grinding on talc and kaolinite morphology Miner Eng 969-976 j.mineng.2005.01.005 318 IARC MONOGRAPHS VOLUME 93 2. Studies of Cancer in Humans 2.1 Occupational exposure 2.1.1 Talc miners and millers Table 2.1 Rubino et al 1976 conducted a study of mortality among men who had begun work in the mines and mills of a talc operation in the Germanasca and Chisone valleys Piedmont Italy between 1921 and 1950 and who had been employed for at least 1 year in a job that involved exposure to talc A total of 1514 miners and 478 millers were identified of whom 168 miners 11.1 and 40 millers 8.4 were lost to follow before the end of the study in June 1974 yielding a combined cohort of 1784 men 89.6 for analysis The talc from these mines was described as pure and was reported to have been used in the pharmaceutical and cosmetics industries However due to the presence of footwall contact rocks and type inclusions in the mines drilling operations were associated with exposure to dusts that contained high levels of silica such inclusions were removed before milling and talc products were reported to have a content of free silica below % The Working Group understood that the term silica was in fact quartz In a few instances talc samples from the area showed small amounts of tremolite when examined by ray diffraction but no amphibolic asbestos or chrysotile were detected For each worker cumulative exposure was estimated from regular measurements of respirable dust content in the air of mines and mills during the period 1948-74 and individual work histories were abstracted from files of the mining company Periods of time during which the dust level was assumed to be uniform were first selected and cumulative exposure was then calculated as the summed product of the number of years in each specific working period years and the associated dust levels million particles per cubic foot mppcf resulting in an overall measure of mppcf Once individual cumulative exposures had been assigned miners and millers were then classified separately into low medium and high levels of exposure Ranges of exposure mppcf_years for miners were 566-1699 1700-5665 and 5666-12750 respectively ranges of exposure for millers were 25-141 142-424 and 425-906 respectively For each of the 1784 workers included 1346 miners and 438 millers one unexposed control subject was chosen at random from among male inhabitants of a nearby small rural town The control was matched to the talc worker on year of birth and vital status at date of entry into the study date not specified Cause of death for 885 95.1 of 931 deceased workers and 1067 94.8 of 1126 deceased controls was obtained from regional death certificate files supplemented with information from relatives physicians and medical records Observed numbers of deaths among talc workers were compared with expected numbers calculated by the use of specific mortality rates experienced by the control cohort The standardized mortality ratio SMR for all causes combined was 0.9 95 Table 2.1 Cohort studies of mortality from and incidence of cancer in populations occupationally exposed to asbestiform tale Reference location Cohort description Exposure assessment Organ site Exposure categories No. of cases deaths Relative risk 95 CI Adjustment factors comments Rubino et al 1992 male talc Occupational history SMR 1976 workers 1514 from plant records All cancers All miners 100 Germanesca and Chisone miners 478 respirable dust millers employed measurements 1948- All millers 42 valleys Piedmont > year in talc- exposed job 1974 quantitative estimation of cumulative Miners mppcf Level 1 566-1699 38 Italy during 1921 exposure for individual Level 2 1700 5665 28 1974 hired 1921- workers expressed as Level 3 5666 12750 34 1950 mortality follow 1921 summed product of duration years and Millers mppcf Level 125 141 125 141 18 74 vital status exposure million Level 2 142 424 13 90 cause of particles per cubic foot Level 3 425-906 11 death 95 of mppcf classification of exposed workers workers into 3 levels of Lung All miners 04 95ofcontrols exposure bronchus and All millers 04 trachea 0.8 0.6 0.9 09 07-12 07-12 07-12 Adjusted for age comparison with unexposed matched controls from 2 0 8 16 neighbouring rural town controls matched on vital 0 0.7 41 9 0 6 12 status at date of entry into study miners and millers exposed TALC TALC 1 0 2 23 to a very pure formoftalc 3 0 2.9 miners also exposed to TALC 07 0.4 72 inhalable silica 5 0.2-09 0.2-09 significantly elevated SMRs for silicosis with and 0 6 0.2 16 without tuberculosis among miners estimates increased Miners mppcf Level 1 566 1699 with increasing cumulative 3 1.1 0.6 1.7 exposure no observed cases Level 1700-5665 1 5 0 7 273 23 of mesothelioma Level 3 5666 12750 5 0 4 1.3 no smoking data for Millers mppcf exposed workers or Level | 25-141 310 1.7 3 439 49 unexposed controls Level 2 142 424 310 1 25 0 07 Level 3 425 906 0 - 319 Table 2.1 contd 320 Reference location Cohort description Exposure assessment Organ site Exposure categories No of cases deaths Relative risk 95 CI Adjustment factors comments Rubino et al 1979 Germanesca and Chisone valleys Piedmont Italy 1678 male talc workers 1260 miners 418 millers mortality follow- up 1946 74 Same exposure categories as Rubino et ~ Lung al 1976 All miners 84 All millers 84 Miners mppcf_years Level 1 566 1699 215 Level 2. 1700-5665 215 Level 3 5666 12750 215 Millers mppcf Level 1 25-141 310 Level 2 142 424 310 Level 3 425 906 310 Selevan et al 392 white male Historical insufficient 1979 talc workers information to calculate All causes Total cohort 90 Vermont 163 miners cumulative exposure Millers 44 USA 225 millers histories cohort Miners 34 employed > year classified into two work between 1940 and = areas mining and All cancers Total cohort 637 1969 mortality milling Millers 637 follow date of first radiogram Miners 637 month employment anniversary or January 1940 Respiratory _ Total cohort 625 cancer Millers 625 Miners 5 whichever was later follow through 1975 vital status 99 cause of death 94 SMR analysis of cohort 0.5 0 2 0.9 reported in Rubino et al 0 7 0 2 17 1976 SMRs recalculated using national death rates instead of comparison with IARC 5 0 190 19 0.2 0 5 12 neighbouring rural population national death 0.6 0 2 41 rates available only from 1951 onward rates for 1951 2 0 0.4 508.4 58 were applied for 1946 50 MONGRAPHS 0.71.7 73 - SMR 1 2 0.9 41 Adjusted for age sex race calendar year US death 1 2 0.9 61 rates 1940-67 linear VOLUME 1.3 0.9 1.8 extrapolation for all causes of death 1967 69 [ 3 0.7 20Vermont death rates for 0.8 0.3 1specific causes of death 93 1.7 07-3.5 07-3.5 1949-75 workers selected from annual radiographic 1.6 6 53 survey ofdusty trades no 1.0 1 73 data on smoking habits for 4 1 4 1)0 millers or miners exposure to radon daughters in mine radiographic evidence of pneumoconiosis in most workers who died from non- malignant respiratory disease Table 2.1 contd Reference location Cohort description Exposure assessment Organ site Exposure categories Wergeland et 389 male talc- Subjective assessment of al 1990 exposed workers exposure by experienced northern and western Norway = 94 miners 295 millers employed > year in mine 1944 colleagues workers classified by total duration of employment in jobs with low 72 or 2 years in = medium high and mill 1935 72 unknown exposure mortality and cancer incidence follow 1953 87 All causes All cancers All cancers Total cohort Miners Millers Total cohort Miners Millers Total cohort Miners Millers Years employed 1-4 5-19 20 Years sincefirst employment 1-19 20-29 30 No of _ Relative risk cases 95 CI deaths Adjustment factors comments SMR Adjusted for age smoking 222 08 08 0.6-09 0.6-09 miners only national 222 0.8 0.5-1 death rates 1953 8m7ain 222 0 7 0 6 0.9 minerals in mined talc deposit were talc and 201 0.8 0 5 1) magnesite 90 of raw 201 1.3 6 52 = material for mill from mine 201 6 4 01 % from India no information on smoking 46 SIR 0.9 0 7 21 habits for millers smoking habits for miners above TALC 15 1.4 0 8 32 national average low levels 31 0.8 5 )1 of exposure to radon daughters 11 1 1 6-2 ) 19 0 8 0 5 12 16 0.9 0 5 1) 682 0 4 2 90 682 [ 1 7 81 22 [ 1 7 61 321 322 Table 2.1 contd Reference location Cohort description Exposure assessment Organ site Exposure categories No of cases deaths Relative risk 95 CI Adjustment factors comments Wergeland et al 1990 contd Lung Total cohort 624 09 03 2003 2003 20 Miners 624 1.6 0 2-5 7 Millers Years employed 624 0.8 0 2-2 ) IARC 1-4 0 - 5-19 33 [ 0 0 2 03 20 33 1.0 0 2-3 0 MONGRAPHS Yearssincefirst employment 1 19 20-29 30 213 1 ]4 213 0 5 1 3 82 213 1 1 0 2-3 2 Stomach Total cohort 6 1 0 4 22 VOLUME VOLUME Miners Millers 633 25 25 0 5-7 4 633 07 07 0 1-2 ) Years employed 1-4 222 20 20 0 2-7 2 93 5-19 222 0 8 0 1 62 20 222 [ 12 0 1-4 3 Years sincefirst employment 1-19 123 0.6 1.4 3.1 20-29 123 1.1 0.1-4 0 30 123 1.7 0 3-4 8 Table 2.1 contd Reference location Cohort description Exposure assessment Organ site Exposure categories No of cases deaths Relative risk 95 CI Adjustment factors comments Wild 2000 Luzenac France 1160 talc workers 1070 men 90 women actively employed in 1945 or hired during 1945-94 and employed > year mortality follow 96 vital status 97 cause of death 74 pre1968 and 98 1968 Exposures assessed for control study semi- All causes quantitative specific exposure matrix based on personal dust measurements 1986 All cancers onwards and subjective assessments by Lung experienced workers workers assigned to four categories of exposure no exposure ambient < mg medium 5 30 mg and high 30 mg exposure prior to hiring also coded = Stomach none probable exposure to quartz certain exposure to quartz exposure to other carcinogens Male talc workers 1968 national rates 101 1968 national rates 294 1968 regional rates 294 1968 regional rates 80 1968 regional rates 21 1968 national rates 21 Men 60 years of age 7 Latency period 20 years = 5 Duration of employment 8 10 years 1968 national rates 5 SMR Adjusted for age sex 08 08 06-10 06-10 smoking prior exposure to 0.8 07-09 07-09 07-09 quartz control study 9 08-1.0 08-1.0 only partial overlap of study population with 1.0 0 8 138 13 Leophonte et al 1983 and Leophonte and Didier 2 0 8 19 1990 extent of overlap 0.9 06-14 06-14 06-14 unknown national mortality TALC rates applied pre- and post- TALC 20 08-4.0 08-4.0 1968 regional mortality TALC 24 24 08-5.6 08-5.6 rates applied 1968 2 9 ]4 excess mortality from lung cancer disappeared when national rates applied 2 04-28 04-28 323 323 323 Table 2.1 contd Reference location Cohort description Exposure assessment Organ site Exposure categories 324 No of _ Relative risk cases 95 CI deaths Adjustment factors comments Wild 2000 contd Nested case- control study lung cancer non- Cumulative exposure estimates years for individual workers Lung malignant pulmonary disease and stomach cancer three randomly selected controls Unexposed 6563 100 years 6563 100 40y0 ears 6563 400-800 years 6563 800 years 6563 Per 100 years 23 Odds ratio 10 4 22 07 Unadjusted odds ratio no increasing trend with increasing cumulative exposure information on smoking habits available for 52 of cases and 09 75 of controls a Assumes linear trend IARC 0 0 9 1.1 per case lung cancer 23 cases 67 controls Wild et al 2002 Luzenac France 1 site and Styrian Alps Austria 4 sites Austrian cohort Austrian cohort semi- 542 male talc quantitative specific All causes workers exposure matrix employed > year based on personal dust during 1972 95 measurements 1988 mortality follow- and descriptions of up 1972 1995 workplaces from vital status 97 management and long- French cohort as term workers workers 92 All cancers Lung described under Wild 2000 assigned to four categories of exposure no exposure ambient < Stomach mg medium 5 30 mg and high 30 mg other exposures coded quartz other carcinogens underground work French cohort Austrian cohort French cohort Austrian cohort French cohort Austrian cohort French cohort Austrian cohort MONGRAPHS SMR Adjusted for age calendar year 294 08-10 smoking exposure to quartz 67 08 06-10 exposure to other carcinogens underground work case VOLUME 80 10 08 1308 1308 13 control study study population 17 0.4 21 overlaps with that of Wild 2000 French SMRs calculated 21 0.8 1.9 by comparison with regional 93 27 14 22rates 1968 9A5ustrian SMRS calculated by comparison with 5 2 0 4 82 regional rates 1972-1995 I 04 0-23 0-23 Austrian smoking information obtained from unpublished mortality studies on pneumoconiosis from colleagues from workers compensation records no missing information on smoking habits in Austrian cohort Table 2.1 contd Reference location Cohort description Exposure assessment Organ site Exposure categories No of cases deaths Relative risk 95 CI Adjustment factors comments Wild et al 2002 contd Nested case- control study lung cancer non- malignant respiratory disease three randomly selected controls per case lung cancer 23 cases 67 controls France 7 cases 21 controls Cumulative exposure Lung estimates m_years assigned to individual workers by occupational physician using work histories abstracted from company records Austria Unexposed 9 /10y0 ears 26753 101 40y0 ears 26753 401 80y0 ears 26753 801 years 26753 Per 100 years 30 Coggiola et al 2003 Piedmont Italy Cohort of 1974 Detailed job histories male talc workers from plant records All causes Total cohort 880 employed > year workers classified on Miners 590 in mine or mill basis of job held miner Millers 290 during 1946 95 versus miller duration of All cancers Total cohort 185 mortality follow- exposure years and time Miners 130 up 1946 9l5oss since first exposure Millers 55 to follow % years Lung cancer Total cohort 44 analysis based on 1244 miners 551 Miners 33 Millers ] millers Years since first exposure 20 808 20-30 808 30 808 Odds ratio Unadjusted odds ratio no trend 10 observed with increasing 09 cumulative exposure trend not 11 affected by adjusting for 06 smoking quartz exposure 07 underground work or by lagging the exposure estimate 09 11Assumesa linear trend TALC SMR Adjusted for age calendar 2 1 1.3 period study population 2 1.4overlaps with that of Rubino et 0 1 al 1976 1979 national death 9 )1 rates used for 1970 period 10 _ 1.3rates for early 1950s used for 0.9 0.6-1 ) 1946-49 regional rates used for 09 07-1.3 07-1.3 1970 9e5xcept for cancers of 7 1.5oral cavity oesophagus and 0.7 0 3 1.2 suicide regional rates unavailable national rates used 04-2.3 ) no information on smoking 05-18 habits no variation in lung 0.9 0.6 13 cancer by duration of exposure 325 326 Table 2.1 contd Reference location Cohort description Coggiola et al contd Exposure assessment Organ site Exposure categories Oral cavity Total cohort No of Relative risk Adjustment factors comments cases 95 CI deaths IARC SMR 3279 5 1 3.5 37 Miners 3279 2 3.9 91) MONGRAPHS Millers Oesophagus _ Total cohort Miners Millers Stomach Total cohort 3279 33 1.3 619.3 69 10 2.1 1.1 3.9 7 2.3 0.9 408.9 48 3 8 0.4 5.2 31 1.2 0.8 1.6 Miners 20 2 0.7 18 VOLUME Millers 11 1 1 0.5 2.0 CI confidence interval mppcf million parts per cubic foot SIR standardized incidence ratio SMR standardized mortality ratio 93 TALC 327 confidence interval CI 0.8 1.f0or miners and 0.9 95 CI 0.8 1.f0or millers No relationship was observed with increasing time between first exposure and death or with increasing cumulative exposure Significant increases in specific cause of death among miners were found for silicosis 62 observed SMR 2.0 95 CI 1.5-2.6 and for silicosis with superimposed tuberculosis 18 observed SMR 2.0 95 CI 1.2 3.1 These estimates were found to increase with increasing cumulative exposure A total of 100 deaths from cancers at all sites combined among miners SMR 0.8 95 CI 0.6 0.9 and 42 deaths among millers SMR 0.9 95 CI 0.7-1.2 were below those expected Nine deaths among miners SMR 0.5 95 CI 0.2-0.9 and four among millers SMR 0.6 95 CI 0.2 1.w6ere due to lung cancer No excess risk for lung cancer was found in the highest exposure category among miners cumulative exposure range 566612750 mppcf five observed SMR 1.1 95 CI 0.4-2.7 or millers cumulative exposure range 425-906 mppcf no observed deaths versus 1.3 expected No cases of mesothelioma were found The Working Group noted that the lack of comparability between the workers and the comparison groups could influence the mortality ratio estimates of this study] In a analysis of their 1976 study Rubino et al 1979 estimated relative mortality among talc workers using Italian national death rates for men instead of the control cohort As national rates were available only for the period 1951-74 end of the study rates for 1951 were applied for the follow period 1946 through to 1950. The number of workers included in this analysis was 1260 miners and 418 millers In contrast to the previous analysis the standardized mortality for all causes combined was significantly increased for miners 560 observed SMR 1.3 95 CI 1.2-1.4 as well as for millers 193 observed SMR 1.2 95 CI 1.0-1.4 Eight observed cases of lung cancer in miners yielded an SMR of 0.5 95 CI 0.2-0.9 and four cases in millers yielded an SMR of 0.7 95 CI 0.2-1.7 No trend was observed with increasing cumulative exposure for either group of workers value for trend not provided Mortality from malignant respiratory diseases was significantly increased among miners 109 observed SMR 3.3 95 CI 2.7-4.0 mainly due to 58 cases of pneumoconiosis and 23 cases of tuberculosis The number of cases of pneumoconiosis and tuberculosis among millers was three and eight respectively Katsnelson and Mokronosova 1979 conducted a study of mortality among male and female workers numbers not specified in a talc mining and processing plant in the former USSR in 1949-75 The tale of the area was reported to contain no tremolite or fibrous materials and levels of quartz ranged from 0.2 to 1.6 Very high mortality ratios were found for cancer at all sites combined relative risks 5.1 for men 6.4 for women 0.001 as well as for lung relative risks 4.5 for men P 0.02 9.3 for women P 0.05 and stomach cancer relative risks 3.7 for men P 0.02 6.3 for women P 0.05 observed numbers of deaths not specified The Working Group noted that the deaths observed among exposed workers included current and past workers but that the denominator comprised only currently employed persons] 328 IARC MONOGRAPHS VOLUME 93 Selevan et al 1979 used radiography records from the annual surveys of workers in dusty trades of the Vermont Health Department to identify all white male workers employed in the Vermont talc industry for at least 1 year between 1940 and 1969. The study covered three areas that had a total of five companies two of which ceased operations in 1952 and 1960 The talc in this region is a mixture of pure talc magnesite chlorite and dolomite Airborne dust samples and bulk materials were free of asbestiform minerals when examined by both ray diffraction and analytical electron microscopy Levels of respirable crystalline silica were below 0.25 in nearly all ore and product samples and free silica was only occasionally detectable in air samples Insufficient information was available to estimate cumulative lifetime exposures but the authors stated that historical data were sufficient to demonstrate past exposure levels for miners and millers far exceeded the standard for fibrous tale of 20 mppcf that was in force at the time of the investigation Due to the more continuous nature of the milling operation it was considered probable that exposures to dust for millers were higher than those for miners In one mine that had closed by the time of the study cobblestones of highly tremolitic serpentine rock were present but were avoided or discarded as far as possible before milling Miners were also exposed to radon daughters at mean levels ranging up to 0.12 working levels WL with single peaks of 1.0 WL The study groups comprised 163 talc miners and 225 millers Vital status of workers was ascertained through to 1975 and death certificates were obtained for 85 of 90 deceased cohort members For non- malignant respiratory disease and respiratory cancer mortality rates for white men from Vermont were used for comparison because they were considered to be more appropriate than national rates For other causes of death rates for the USA were used Some increase was noted for all malignant neoplasms combined 16 observed SMR 1.3 95 CI 0.7 2.0 and specifically for respiratory cancer six observed SMR 1.6 95 CI 0.6 3.5 The Working Group noted that the results for respiratory cancer were not analysed by latency The excess mortality from respiratory cancer was statistically significant among the miners five observed SMR 4.3 95 CI 1.4-10.1 but not among the millers two observed SMR 1.0 95 CI 0.1-3.7 A significant excess of mortality from nonmalignant respiratory disease was seen in millers seven observed SMR 4.1 95 CI 1.6-8.4 but not in miners two observed SMR 1.6 95 CI 0.2-5.9 Most workers who died from malignant respiratory disease had radiographic evidence of pneumoconiosis rounded opacities In two brief communications Leophonte et al 1983 and Leophonte and Didier 1990 reported on the mortality of workers employed in a talc quarry in Luzenac in the South of France and in the associated talc processing plant The cohort was composed of those who left employment between 1945 and 1981 and who had worked at the plant for more than 1 year The talc in this region is a mixture of pure talc chlorite and dolomite with no asbestos levels of quartz vary from 0.5 to % Of 470 workers available for study 256 were alive 209 had died and five were lost to follow Of 204 workers with a known job history and date of death 192 had worked exclusively with talc at Luzenac No significant excess of mortality from cancer in general or specifically from respiratory TALC 329 and digestive cancers was found Observed and expected numbers of specific deaths and associated relative risks were not given A significant increase in mortality was found for malignant respiratory disease especially for pneumoconiosis and obstructive lung disease No cases of mesothelioma were observed The Working Group noted the unconventional definition of the cohort and that causes of death were obtained differently for cases from local doctors hospitals or families and controls from regional or national records] Wergeland et al 1990 studied 94 male workers at a tale mine in northern Norway who had been employed in exposed jobs for at least 1 year during 1944-72 and 295 male workers at a talc mill in western Norway who had been employed for at least 2 years during 1935-72 Data on miners were gathered from the company pay rolls lists of union memberships and the central registry of workers exposed to silica in Norway data on millers were collected from the company protocol and the local occupational health service The information included name date of birth first and last date of employment and number of periods of employment According to the authors Norwegian talc contains only trace quantities of quartz tremolite and anthophyllite as determined by optical microscopy and by electron microscopic analysis The talc in the region where the mine was located is composed mainly of pure talc and magnesite Approximately 90 of the raw material in the mill came from the mine and the rest was imported from India In addition to talc dolomite and mica were also processed at the mill Personal air samples collected in the early 1980s showed that total dust levels varied greatly by job category and workplace mine 0.9-97 mg mill 1.4-54 m Peak exposures occurred during drilling in the mine 319 mg and in the store house in the mill 109 mg Ray diffractometry indicated that dust samples from both operations contained less than % quartz The mean value for concentrations of radon daughters in the mine was 3.5 pCi 0.04 WL with a range of 1.5-7.5 pCi 0.02-0.08 WL The majority of the 389 workers could be classified into one of three categories according to degree of dust exposure based on measurements and qualified assessments of dust level by experienced workers Information on tobacco smoking habits gathered during the study in 1981 was available for 63 of the 94 miners and showed that smoking rates among these workers were above the national average Follow for cancer incidence through data linkage to the national cancer registry and specific mortality through linkage to the national mortality files was begun at the date of entry into the cohort or 1 January 1953 whichever came later and ended at date of death or 31 December 1987 whichever came first National rates were used to calculate expected numbers of cancers and deaths The SMR for all causes for the total cohort was 0.8 117 observed 95 CI 0.6-0.9 which reflected a decrease among both miners 27 observed SMR 0.8 95 CI 0.5- 1.2 and millers 90 observed SMR 0.7 95 CI 0.6 0.A9n excess of deaths from all cancers was observed in miners nine observed SMR 1.3 95 CI 0.6 in either the total cohort 26 observed SMR 0.8 95 CI 0.5-1.1 or 2.b5ut not in millers 17 observed SMR 0.6 95 CI 0.4-1.0 Mortality from malignant respiratory diseases was decreased with one observed death among miners SMR 0.4 95 CI 0 330 IARC MONOGRAPHS VOLUME 93 2.2 and two observed deaths among millers SMR 0.2 95 CI 0-0.9 No deaths from pneumoconiosis were reported The standardized incidence ratio SIR for all types of cancer combined was 1.4 15 observed 95 CI 0.8-2.3 among the miners and 0.8 31 observed 95 CI 0.5 1.a1mong the millers Two cases of lung cancer were observed among miners SIR 1.6 95 CI 0.2 5.a7nd four cases among millers SIR 0.8 95 CI 0.2-2.0 The significant excess risk among the miners was confined to cancer of the stomach three observed SIR 2.5 95 CI 0.5-7.4 and cancer of the prostate four observed SIR 2.0 95 CI 0.6 5.02.6 5.2In the subgroup of 80 workers who belonged to the highest exposure category a total of six cases of cancer were observed SIR 0.4 95 CI 0.2-1.0 none of which were cancer of the lung There were no observed cases of mesothelioma Wild 2000 conducted a retrospective cohort mortality study within a nested case- control study at the same talc quarry and milling plant at Luzenac as that used by Leophonte et al 1983 and Leophonte and Didier 1990 The cohort included employees who were active in 1945 or hired in the milling plant during the period 194594 and who had been employed continuously for at least 1 year Employees who were identified from the company files comprised a total of 1070 men and 90 women The authors did not indicate the extent of overlap of the study population with that investigated by Leophonte et al 1983 and Leophonte and Didier 1990 Dust levels in the 1960s and 1970s were generally high ranging from below 5 mg to more than 30 mg Average dust levels dropped to below 5 mg in the 1990s through process changes and installation of engineering controls e.g. installation of a central vacuum follow system Overall mortality of the cohort was evaluated from 1 January 1945 to 31 December 1996. Vital status was obtained from the local population register and national mortality files which also included information on cause of death in most cases for individuals who died after 1968. Overall 32 2.8 employees were lost to Of 106 individuals who died before 1968 cause of death was ascertained for 78 cases SMRs were calculated using both regional mortality rates pre- and 1968 and national mortality rates 1968 When regional mortality rates for 1968 and later were used the SMR for all causes of death combined was 0.9 294 observed 95 CI 0.8-1.0 for men and 0.8 11 observed 95 CI 0.4-1.4 0.4-1.4 for women Eighty men died from cancer at any site SMR 1.0 95 CI 0.8-1.3 and 21 died from lung cancer specifically SMR 1.2 95 CI 0.8-1.9 Mortality from lung cancer was significantly increased in subgroups of employees who were under 60 years of age seven observed SMR 2.0 95 CI 0.8-4.0 had a latency period of less than 20 years five observed SMR 2.4 95 CI 0.8-5.6 or had a duration of employment of less than 10 years eight observed SMR 2.1 95 CI 0.9-4.1 A slightly increased risk was seen for stomach cancer five observed SMR 1.2 95 CI 0.4-2.8 Twenty men died from non- malignant respiratory diseases SMR 1.1 95 CI 0.7-1.6 three of which were pneumoconiosis SMR 5.6 95 CI 1.1 16.W2hen 1968 national reference rates were applied the overall SMR for men was 0.8 101 observed 95 CI 0.6 1.a0nd the excess mortality from lung cancer and malignant respiratory diseases disappeared Of TALC 331 the 101 deaths observed during this period one was caused by lung cancer SMR 0.3 95 CI 0.7-1.5 and five were caused by malignant respiratory diseases SMR 0.7 95 CI 0.2-1.6 A nested control study was performed to investigate further the risks for lung cancer stomach cancer and malignant respiratory diseases in the men of the cohort For the lung cancer control study 67 controls were individually matched to the 22 cases by age and sex approximately three controls per case Information on job history at the plant and tobacco consumption was collected through interviews of subjects who were alive and from experienced workers A semiquantitative specific exposure matrix for talc dust was established using dust levels measured from 1986 onwards and estimates of levels before that year Information on job history was then converted into estimates of cumulative exposure of the individual employees expressed as years Multiple logistic regression analysis with adjustment for tobacco smoking habits and exposure to quartz estimated the odds ratio for lung cancer to be 0.7 three cases and 15 controls and 0.9 three cases and 10 controls for employees with a cumulative exposure to talc dust of 400-800 years and more than 800 years respectively when compared with unexposed employees six cases and 20 controls The Working Group noted that information on smoking habits was available for only 52 of cases and 75 of controls and that no specific information was given on the proportion of subjects alive among cases and controls at the date of interview] Wild et al 2002 conducted a combined analysis of previously published cohort mortality studies among 1070 male employees at a tale quarry and milling plant in the south of France Site A Wild 2000 and 542 male employees at three talc mines and their respective mills in Austria Sites B C and D The Austrian cohort comprised workers who had been employed for at least 1 year between 1 January 1972 and 31 December 1995. Complete work histories for the Austrian workers were abstracted from company registries and from the regional social insurance Information on tobacco smoking habits was obtained from earlier unpublished studies of mortality and pneumoconiosis from colleagues and from records of the compensation claim insurance Talc from two of the three Austrian plants Sites B and C had a content of quartz that was less than % while that of the third plant Site D had higher but unspecified levels Vital status of workers was verified through to 1995 and cause of death for those who had died was obtained from national mortality files Local mortality rates yielded an overall SMR for the Austrian cohort of 0.8 67 observed 95 CI 0.6-1.0 A total of 17 deaths were due to cancer at any site SMR 0.7 95 CI 0.4-1.2 seven of which were from cancer of the lung SMR 1.1 95 CI 0.4-2.2 One death from stomach cancer SMR 0.4 95 CI 0-2.3 and no deaths from mesothelioma 0.1 expected occurred On the basis of 23 lung cancer deaths observed in the French cohort in 196896 and seven in the Austrian cohort in 1972-95 a nested control study was conducted A total of 88 control subjects were selected from the two cohorts individually matched to cases on age calendar period and company All job tasks at the companies were categorized according to measured and estimated levels of talc dust into one of four 332 IARC MONOGRAPHS VOLUME 93 exposure groups no exposure < 5 mg 5-30 mg and > 30 mg Job histories of cases and controls were converted into cumulative exposure to talc dust by summing the products of duration and level of exposure for each of the tasks held by the subject years Subjects were also categorized according to tobacco smoking habits exposure to quartz or a history of underground work on a yes basis Information on smoking habits was available for approximately 50 of the cases and 75 of the controls in the French cohort and for 100 of the Austrian cohort When the exposure category was used as the standard nine cases 23 controls the unadjusted odds ratios for lung cancer were as follows 0.9 exposure category 1-100 years six cases 18 controls 1.1 exposure category 101-400 years seven cases 15 controls 0.6 exposure category 401-800 years five cases 21 controls and 0.7 exposure category > 801 years three cases 10 controls Assuming a linear trend the odds ratio was 1.0 95 CI 0.9 1.p1er unit of 100 years Adjustment for tobacco smoking exposure to quartz or underground work or any two of these variables did not change the results Coggiola et al 2003 updated the cohort of Rubino et al 1976 1979 to include 1974 men who had worked for at least 1 year in the mine and in the factory during the period 1946-95 The mortality analysis included 1795 subjects 90.9 of the total cohort 1244 miners and 551 millers after excluding 179 workers who were lost to follow No data on smoking habits were available Follow began on 1 January 1946 or the date of first employment and ended at the date of death or 31 December 1995 during which time a total of 880 deaths occurred The expected number of deaths was calculated from national rates for 1950-69 and regional mortality rates for 1970 onwards with the exception of cancers of the oral cavity and oesophagus for which regional rates were unavailable national rates were therefore used Rates for the early 1950s were applied for the period 1946-49 Total mortality among workers was higher than expected 880 observed SMR 1.2 95 CI 1.1-1.3 mainly due to excess mortality from nonmalignant respiratory tract diseases among the subgroup of miners 105 observed SMR 3.1 95 CI 2.5-3.7 Of the 105 deaths in this category 58 were from silicosis In the combined cohort of workers there was no excess mortality for all cancers 185 observed SMR 1.0 % CI 0.9-1.1 or for lung cancer in particular 44 observed SMR 0.9 95 CI 0.7-1.3 No deaths from pleural or peritoneal mesothelioma were found A significantly elevated risk was seen for cancers of the oral cavity 31 observed SMR 5.1 95 CI 3.5 7.a3nd the oesophagus 10 observed SMR 2.1 95 CI 1.1 3.W9hen the analysis was stratified by job the SMR for lung cancer was 1.1 33 observed 95 CI 0.7-1.5 among miners and 0.7 11 observed 95 CI 0.3-1.2 among millers The slight excess found among miners seemed to be due to a slightly elevated risk in workers with less than 20 years since first exposure latency six observed SMR 1.1 95 CI 0.4 2.3 compared to that of workers with 20-30 years 10 observed SMR 1.0 95 CI 0.5 1.8 and more than 30 years 28 observed SMR 0.9 95 CI 0.6-1.3 since first exposure There was no variation in lung cancer mortality by duration of exposure Cancer of the oral cavity caused the death of 24 miners SMR 6.2 95 CI 3.9 9.a1nd TALC 333 seven millers SMR 3.3 95 CI 1.3-6.9 and oesophageal caused the death of seven miners SMR 2.3 95 CI 0.9-4.8 and three millers SMR 1.8 95 CI 0.4-5.2 Excess mortality was seen in miners for malignant respiratory tract diseases 105 observed SMR 3.1 95 CI 2.5-3.7 malignant digestive tract diseases 50 observed SMR 1.4 95 CI 1.0-1.8 and liver cirrhosis 37 observed SMR 1.8 95 CI 1.3-2.5 An increased risk for liver cirrhosis was also observed in millers 18 observed SMR 1.7 95 CI 1.0 2.7 analysis ofriskfor lung cancer Wild 2006 performed a analysis of lung cancer mortality among miners and millers from industries that produced asbestiform talc in Vermont USA Selevan et al 1979 Norway Wergeland et al 1990 Italy Coggiola et al 2003 France Wild 2000 and Austria Wild et al 2002 The purpose of the analysis was to compute risk estimates separately for talc miners who usually have some exposure to silica and radon daughters and talc millers who normally have no such exposure Previously unpublished risk estimates for the subgroup of millers in the French and Austrian cohorts were used and additional information on smoking habits was obtained for Italian French and Austrian workers Data indicated that the prevalence of smoking was higher than that in the reference populations figures not specified In the estimation of the overall risk for millers data from all five countries were used while only data from the USA Norway and Italy were included in that for miners Based on SMRs for lung cancer of 1.0 USA two cases 95 CI 0.1-3.7 0.7 Italy 11 cases 95 CI 0.3 1.12.2 France 21 cases 95 CI 0.8 1.09.7 Austria Site B three cases 95 CI 0.1-2.0 and 1.1 Austria Site C one case 95 CI 0 6.a2nd an SIR of 0.8 Norway four cases 95 CI 0.2 2.0 for talc millers a summary SMR of 0.92 42 cases 95 CI 0.7-1.3 was obtained No heterogeneity between studies was detected Similarly based on mortality ratios for lung cancer of 4.4 USA five cases 95 CI 1.4-10.2 and 1.1 Italy 33 cases 95 CI 0.7-1.5 and an incidence ratio of 1.6 Norway two cases 95 CI 0.2-5.7 for talc miners a summary SMR of 1.2 40 cases 95 CI 0.9-1.6 was found Due to a significant heterogeneity of the latter data set a random effect estimate of the overall SMR was also calculated 40 cases SMR 1.9 95 CI 0.7-5.1 2.1.2 User industries Table 2.2 Information on risk for cancer among workers exposed to talc is available from studies that were conducted in user industries However they are less informative than those conducted in talc miners and millers because the potential contamination of talc was not addressed In addition these studies provided no details about the type of talc used a Manufacture ofceramic plumbingfixtures Thomas and Stewart 1987 conducted a cohort mortality study of 2055 white men employed for at least 1 year between 1939 and 1966 at three plants of a single company in 334 Table 2.2 Cohort studies of mortality from and incidence of cancer in workers occupationally exposed to asbestiform tale in user industries Reference location Cohort description Exposure assessment Organ site Exposure categories No. of cases deaths Relative risk 95 CI Adjustment factors comments Manufacture ofceramic plumbing fixtures Thomas & 2055 white men Exposure to silica and Stewart employed > talc assessed qualitatively All causes Total cohort 587 1987 USA yearm 1939 66 by job department Lung cancer Total cohort 52 5 plants in 1 mortality follow- by industrial hygienist High silica 44 company up through to High fibrous 21 1 Jan 1981 vital talc status 96 High fibrous 5 fibrous talc High silica talc 18 Manufacture ofpulp and paper Langseth & Andersen 1999 Norway 10 paper mills 4247 women employed > year 1920 93 follow of cancer incidence 1953-93 All cancers Total cohort 380 Ovarian 37 cancer Exposure 31 y3ears Age 25-35 6 years Ovarian Paper mill workers 18 cancer SMR Crystalline silica was the 0 0 8 10 major exposure also IARC 4 1 1 19 exposure to fibrous and 1.8 1.3 2.4 fibrous talc 2.5 1 6 3.9 17 06-4.0 06-4.0 14 14 08-22 08-22 08-22 MONGRAPHS MONGRAPHS SIR Comparison with year 1.2 (1 1-13) specific rates in VOLUME 1.5 (1 1-1 2) 6 1 1 2.3 Norwegian women cancer incidence from National Cancer Registry 93 80 29 17429 17249 174 2 3 3.4 Table 2.2 contd Reference location Cohort description Exposure assessment Organ site Exposure categories No of cases deaths Relative risk 95 CI Adjustment factors comments Langseth & Kjaerheim 2004 Norway 10 paper mills Nested case- control study in cohort of Langseth & Andersen 1999 46 cases 179 matched controls 100 histologically confirmed Exposure to asbestos talc and total dust from work histories questionnaires by industrial hygienists senior employees and international database personal use oftalc 76 ofcases 57 of controls personal interviews Ovarian cancer Total dust Ever talc Ever asbestos Asbestos according to interview Rubber manufacturing industries Blum et al Nested case- Exposure to polycyclic Stomach Company A 1979 USA control study 100 hydrocarbons cancer moderate talc 22 2 rubber cases 4 controls nitrosamines carbon High talc 22 companies per case matched _ black talc high on age race sex moderate low none company 196473 from job histories Odds ratio 0.8 0 4 1.7 1.1 06-22 06-22 06-22 2.0 0.7 75 2.2 0 5 )9 Parity breastfeeding tobacco smoking habits family history of breast or ovarian cancer conditional logistic regression odds ratios unchanged after adjustment for confounders TALC 2.4 ( 4 *4 3 0 9 *2 No information on composition or purity of talc no increase in risk in Company B 90 CI 335 336 Table 2.2 contd Reference location Cohort description Exposure assessment Organ site Exposure categories Straieft al 1999 Germany 5 rubber production plants 8933 male blue- = Work histories collar workers recontructed from cost hired after | Jan. centre codes 1950 and alive 1 Jan 1981 follow 1 Jan 1981 to end of 1991 cause of death known for 97 of 1521 deceased Lung cancer Stomach cancer Straieft al 2000 Germany 5 rubber production plants Same as that of Straif al 1999 Same as Straieft al 1999 plus semiquantitative cumulative exposure low medium high to asbestos talc nitrosamines carbon black for 95 of cohort Lung cancer Stomach cancer Laryngeal cancer High talc Medium talc High talc Medium talc High talc Medium talc CI confidence interval SIR standardized incidence ratio SMR standardized mortality ratio No of cases deaths Relative risk 95 CI Adjustment factors comments SMR SMRS calculated from IARC 154 2 1 0 1.4 national death rates 44 1 2 0.8 1.6 MONGRAPHS 21 1.9 1 1 3) Unadjusted reference low VOLUME 27 1 1 0 8 168 16 exposure to talc 11 4.3 2 1 9.0 23N 2 6 42 23N 5.4 1 1 207 93 23N 28 28 05-167 05-167 05-167 TALC 337 the USA that manufactured ceramic plumbing fixtures Crystalline silica was said to be the major occupational exposure of these workers but in some parts of the plant exposure to fibrous tremolitic and fibrous tremolite talc had also occurred Vital status was ascertained for 96 of the cohort through to 1 January 1981 and observed numbers of deaths were compared with numbers expected from specific mortality rates for white men in the USA For each job department combination exposure to silica and talc were qualitatively assessed by an experienced industrial hygienist Silica exposure was categorized as none low or high high exposure to silica was further categorized on the basis of no exposure to talc exposure to fibrous talc and exposure to fibrous talc The SMR for all causes combined was 0.9 578 observed 95 CI 0.8 1.a0nd that for lung cancer was 1.4 52 observed 95 CI 1.1-1.9 The excess mortality from lung cancer was seen exclusively among workers who had been exposed to high levels of silica dust 44 observed SMR 1.8 95 CI 1.3 2.a4nd to a greater extent in the subgroup with additional exposure to fibrous tale 21 observed SMR 2.5 95 CI 1.6-3.9 than in subgroups with additional exposure to fibrous talc five observed SMR 1.7 95 CI 0.6-4.0 or no exposure to talc 18 observed SMR 1.4 95 CI 0.8-2.2 The Working Group noted that all jobs that involved exposure to talc also involved high exposure to respirable silica b Manufacture ofpulp andpaper Langseth and Andersen 1999 examined cancer incidence among a cohort of 4247 women who had been employed for at least 1 year between 1920 and 1993 in the Norwegian pulp and paper industry The women had worked mainly in paper sorting and packing departments in 10 paper mills or in administration 85 of the cohort Production was judged to involve occupational exposures that included paper dusts microbes formaldehyde talc and asbestos the latter was used as insulation material in boilers and in the breaks of various rolling machines but no measurement data were available Women were followed for cancer incidence between 1953 and 1993 and SIRS were calculated by comparing the observed incidence to the year specific incidence rates for the female population of Norway Information on cancer incidence was obtained by linkage with the National Cancer Registry and information on dates of death and emigration was obtained from the Central Bureau of Statistics of Norway Records of women who died between 1953 and 1960 were identified manually Between 1953 and 1993 535 women in the cohort had died 65 women had emigrated and 380 new cases of cancer had been diagnosed The SIR for all cancers was 1.2 380 observed 95 CI 1.1- 1.3 An excess of ovarian cancer diagnoses was observed 37 observed SIR 1.5 95 CI 1.1-2.1 In the analyses workers were also stratified by exposure into the following categories short < years versus term y3ears period of first exposure 1920-39 1940 519960 741975 9a3nd time since first exposure 3-14 years 15 29 years 30 years The excess risk was predominantly seen among women who had been employed in the industry for 3 years or more 31 observed SIR 1.6 95 CI 1.1 2.3 The excess risk for ovarian cancer was also highest for women under the age of 338 IARC MONOGRAPHS VOLUME 93 55 years at diagnosis with an SIR of 8.0 six observed 95 CI 2.9 17.f4or aged 25-35 years at diagnosis Among women who worked in the paper mills the ovarian cancer was 2.1 18 observed 95 CI 1.3-3.4 In the discussion the noted that tale is added as a filler in paper mills and may contribute to the excess ovarian cancer observed women SIR for authors risk for On the basis of an extended follow of cohort members for cancer incidence to the end of 1999 Langseth and Kjaerheim 2004 conducted a nested control study that included 46 employees who had ovarian cancer and 179 controls individually matched to cases by incidence density sampling An experienced oncologist reviewed the pathology for all cases Work histories were obtained from personnel records at each mill Exposure to asbestos talc and total dust was assessed on the basis of the work histories questionnaires on production processes completed by industrial hygienists and senior employees as well as semiquantitative exposure assessments for the 10 mills extracted from an international database of exposure in the pulp and paper industry Information on possible confounders including use of talc on sanitary napkins underwear or diapers was obtained for 76 of cases and 57 of controls through a personal interview with the study subject or next of kin Odds ratios for ovarian cancer were derived by conditional logistic regression Ever exposure to asbestos was associated with a significantly increased odds ratio for ovarian cancer of 2.0 95 CI 0.7-5.7 while ever exposure to talc odds ratio 1.1 95 CI 0.6-2.2 or to total dust odds ratio 0.8 95 CI 0.4-1.7 0.4-1.7 was associated with risks that were close to unity Among women who were interviewed the odds ratio for exposure to asbestos was 2.2 95 CI 0.5-9.1 This estimate was unchanged after adjustment for multiple potential confounders including parity breastfeeding tobacco smoking habits and family history of breast or ovarian cancer The odds ratios for occupational exposure to talc and total dust were similarly unchanged after adjustment for confounding c Rubber manufacturing industries Following the finding of an excess risk for stomach cancer in a cohort of rubber workers in the USA Blum et al 1979 carried out a nested control study of stomach cancer Cases were defined as deaths from stomach cancer in two of the rubber companies from 1 January 1964 to 31 December 1973 100 deaths in total Four controls were matched to each case on age race sex and company Using the recorded job history of each worker the investigators and a group of environmental scientists assessed the potential for exposure high moderate low or none in each job to the following substances polycyclic hydrocarbons nitrosamines carbon black and detackifiers antisticking agents which were mainly talc No information was available on the purity or composition of the talc i.e. whether it contained asbestiform materials or other fibrous or fibrous carcinogens While no clear elevation of odds ratio was reported in Company B a significantly increased relative risk of 2.4 27 observed 90 CI 1.4 4.1 was found in Company A when workers with moderate and high exposure to talc were TALC 339 pooled into one group High exposure in the latter increase in relative risk of 1.3 13 observed 90 CcIo0m.p7a-n2y.w5as associated with a modest Based on the employment files of five rubber al 1999 conducted production plants in Germany Straif et a mortality cohort study of 8933 male collar workers who hired after 1 January 1950 and who were alive on 1 January 1981. Follow was stwaretreed on the date of completion of 1 year of employment or 1 January 1981 whichever came last and ended on at death at 85 years of age at the date of loss to 31 December 1991 whichever came first Cause of death was obtained ffoorll9o7w oorf 1521 deceased workers Work histories were reconstructed from cost centre codes and were classified into six work areas SMRs were calculated from national death rates and were estimated at 1.2 154 observed 95 CI 1.0-1.4 for lung cancer and 1.2 44 observed 95 CI 0.8-1.6 0.8-1.6 for stomach cancer In a subsequent analysis Straif et al 2000 information on work history was combined with semiquantitative levels of exposure to asbestos talc nitrosamines and carbon black that were estimated by industrial hygienists to yield overall estimates of cumulative exposure low medium high for approximately 95 of the cohort Talc is widely used in rubber production and according to the authors asbestos was used in all five plants at least until the early 1980s In risk analyses that were unadjusted for exposure to asbestos or other potential workplace confounders high and medium occupational exposure to talc were associated with relative risks for lung cancer of 1.9 21 observed 95 CI 1.1-3.1 and 1.1 41 observed 95 CI 0.8 1.6respectively when workers with low exposure were used as the reference group Equivalent risk estimates were 4.3 11 observed 95 CI 2.1-9.0 and 1.2 12 observed 95 CI 0.6-2.4 for stomach cancer and 5.4 three observed 95 CI 1.1-27.0 and 2.8 two observed 95 CI 0.5-16.7 for laryngeal cancer Separate risk analyses with adjustment for potential confounders were not performed The Working Group noted that risk analyses that adjusted for estimates of exposure to asbestos were not presented] 2.1.3 Community studies Chen et al 1992 conducted a control study in Beijing China of several risk factors for ovarian cancer that included occupational exposure to talc A total of 220 cases of newly diagnosed epithelial ovarian cancer were identified between 1984 and 1986 through the Beijing Cancer Registry Of these 67 30.5 were excluded due to 37 16.8 due to unavailability of current contact information and four 1.8 ddueeattho patient refusal The analysis was carried out on 112 112 cases and 224 community controls with two matched controls per case Potential controls were excluded if they had a history of serious illness although the percentage of those excluded for this reason was not specified In addition 15 of the 224 eligible controls initially selected 6.7 refused to participate in the study and were therefore replaced by other eligible controls No information was provided on the age range of the cases and controls although the mean age at the time of interview was similar for cases 48.5 years and controls 49.0 years 340 IARC MONOGRAPHS VOLUME 93 All cases were confirmed by laparotomy and pathological review Data were collected in- person by trained interviewers Odds ratios were estimated using conditional logistic regression adjusted for education and parity Occupational exposure to talc was with an odds ratio for ovarian cancer of 0.9 95 CI 0.3 associated 2.9The Working Group noted the incomplete ascertainment of cases of ovarian cancer due to the nature of the reporting system in China the large number of cases who were excluded due to death and the exclusion of controls who had a history of serious health problems which may have resulted in selection bias] Hartge and Stewart 1994 analysed the occupational histories of 296 20-79 years who were diagnosed with ovarian cancer between 1978 and w1o9m8e 1 ninagtehde Washington DC area of the USA and 343 hospital controls matched to and race Pathology was confirmed for all cases Trained interviewers used a sctaasnedsaordniazgede questionnaire to obtain information from each participant on their lifetime job history and occupational exposure to talc An industrial hygienist blinded to the case status of each participant evaluated each industry and occupation for potential exposure to talc ionizing radiation polycyclic aromatic hydrocarbons and solvents using a scale of 0 definitely not exposed to 4 definitely exposed Women were considered to be exposed if they had an exposure rating of 2-4 possibly probably or definitely exposed Logistic regression adjusted for race age parity gynaecological surgery and duration of employment in jobs with the exposure of interest was used for the analyses Controlling for additional known and potential risk factors for ovarian cancer including parity oral contraceptive use and cigarette smoking did not change these estimates Women who were classified as been having occupationally exposed to talc had odds ratios below the null although the confidence limits were wide due to the small number of exposed women 12 cases 31 controls For women with 10 or more years of employment in an occupation with possible probable or definite exposure to talc the odds ratio was 0.5 five exposed cases 95 CI 0.2 1.5The risk for ovarian cancer was not significantly elevated for any exposure or duration of employment assessed Limitations of this analysis include the small number of women occupationally exposed to talc Industrial talc was one of the substances evaluated by the exposure assessment team in the community control study carried out in Montr^'alCanada Siemiatycki 1991 and described in detail in the monograph on carbon black About % of the 4263 study subjects was considered to be exposed to industrial talc mostly in the following occupations painters motor vehicle mechanics and farmers Exposure to talc was analysed in relation to 11 different types of cancer at two levels of exposure any or substantial No statistically significant increases in risk were observed The odds ratios for lung cancer were 0.9 35 exposed cases 90 CI 0.6 1.f4or any exposure and 0.9 nine exposed cases 90 CI 0.5 1.09.5 1.9for substantial exposure Prostate cancer was the only site with a borderline significant increased risk with an odds ratio of 1.4 29 exposed cases 90 CI 1.0-2.1 for any exposure and 1.1 seven exposed cases 90 CI 0.5-2.3 for substantial exposure The main limitation of the study was the reliance on expert opinions of exposure rather than measurements for exposure TALC 341 assessment Also exposure levels tend to be lower in such in the workplaces that are selected for community studies than cohort studies The main advantages were the availability of histologically confirmed incident cases and detailed information on tobacco smoking habits and other characteristics of the subjects ] 2.2 Cosmetic use of talc This evaluation was limited to ovarian cancer because the Working unaware of studies of other cancers associated with the cosmetic use of talc Group was The content of body powders used by women varies by product and has changed over time although data that document this are limited Before the 1970s body powders may have contained varying but usually small quantities of amphiboles After that time amphibole was voluntarily reduced to less than detectable levels at least in western Europe and the USA Other non minerals that include chlorite quartz carbonates and pyrophyllite may also be found in body powders in varying and occasionally not insignificant quantities in the past and currently Other added ingredients which depend on the product could include cornstarch and perfumes 2.2.1 Cohort studies Gertig et al 2000 carried out the only prospective cohort analysis that reported an association between perineal use of talcum baby or deodorant powder and the risk for ovarian cancer This analysis was conducted among participants in the Nurses Health Study a cohort of 121 700 female registered nurses who had been followed since 1976 All participants were between the ages of 30 and 55 years and lived in one of 11 states of the USA at study enrolment Questionnaires were mailed to participants every 2 years beginning in 1976 to obtain information on the medical history of each woman and potential risk factors for cancer heart disease and other conditions The 1982 questionnaire requested information on history and frequency of application of powder to the perineal area none daily one to six times a week less than once a week and history of application of powder to sanitary napkins yes Ever talc use was classified as ever use on either the perineal area or on sanitary napkins The study population included 78 630 women who responded to the questions on powder use in 1982 and who were not excluded from the analysis for another reason cancer other than melanoma skin cancer before 1982 bilateral oophorectomy surgery with unknown number of removed or radiation therapy and entailed 984 212 person of follow Beotvawreieens 1982 and June 1996 307 incident cases of epithelial ovarian cancer were identified by reporting in a biennial questionnaire by deaths that were reported by relatives or postal authorities or through the National Death Index Physicians blinded with respect to exposure status reviewed pathology reports to confirm each case and to determine the histological subtype for each tumour as reported by the woman's pathologist Pooled logistic regression was used to model the incidence rate ratio of ovarian cancer for the 342 IARC MONOGRAPHS VOLUME 93 exposed versus unexposed participants The reported results were adjusted for age in years parity defined as the number of pregnancies lasting 6 months or more duration of aornadl contraceptive use body mass index history of tubal ligation tobacco smoking status postmenopausal use of hormones Additional covariates considered confounders included at as potential age menarche duration of breastfeeding and age at menopause Family history of ovarian cancer was not considered to be information on this covariate a confounder since was not collected until 1992. In 1982 40.4 of the cohort reported a history of perineal talc use n 31 789 and 14.5 reported a history of daily use n = 11 411 Overall no association between ever use of talcum powder and total risk for epithelial ovarian cancer relative risk 1.1 95 CI 0.9-1.4 and no trend of increased risk for ovarian cancer with increasing frequency of talc use were observed However a modest increase in risk for serous invasive cancers was associated with history of talc use relative risk 1.4 95 CI 1.0 any 1.a9nd a borderline significant trend was found with increasing frequency of use p for trend = 0.05 Among women without a history of tubal ligation no association was observed between history of talc use and total risk for epithelial ovarian cancer relative risk 1.0 95 CI 0.7-1.3 0.7-1.3 Similarly history of tubal ligation did not modify the association between the use of talc and risk for serous invasive cancers Limitations of this analysis include the availability of information at a single point only the relatively short follow exposure period after ] exposure assessment and the lack of information on age at first use of talc duration of use of talc current use of talc in 1982 and use of talc before tubal ligation or all of which are pregnancy potentially important parameters based on previous studies 2.2.2 control studies Table 2.3 Cramer et al 1982 reported the first epidemiological study of genital talc use and the risk for ovarian cancer The analysis included 215 cases of epithelial ovarian cancer and 215 population controls matched to cases by age within 2 years race and residence All cases were Caucasian speaking residents of Massachusetts USA aged 18-80 years who had been diagnosed with epithelial ovarian cancer between November 1978 and September 1981. Cases were identified through pathology logs or tumour boards of 12 participating Boston hospitals Among 297 eligible cases identified during the time period of interest 41 were excluded from the study due to physician refusal 13 patient refusal 14 or change of address 14 An additional 41 cases were excluded because they had a ovarian primary 18 or a epithelial ovarian tumour based on a review of pathology specimens by the authors Controls were identified though annual listings of the names addresses and ages of all Massachusetts residents Among 475 women identified as potential controls 11.8 56 could not be reached 6.1 29 were ineligible due to previous bilateral oophorectomy 4.2 20 were the wrong age not Caucasian or did not speak English and 32.6 155 refused to participate All cases and controls were interviewed in person to obtain information on their medical history menstrual and reproductive histories as well as potential for exposure Table 2.3 control studies of epithelial ovarian cancer invasive or borderline and cosmetic use of talc Reference study location study period Characteristics of cases Exposure assessment and controls Exposure categories No. of Odds ratio exposed 95 CI cases Adjustment for potential confounders Comments Cramer et al 215 Caucasian 1982 speaking Boston MA women aged 18 80 USA 1978 81 years identified through pathology logs or tumour boards of 12 Boston hospitals histological confirmation of person interviews information collected on medical history menstrual and reproductive history potential or definite exposure to talc Any perineal 92 exposure to talc As dusting 32 powder on perineum and sanitary napkins diagnosis 215 population controls identified through annual listings of names ages and addresses of all Massachusetts residents matched by age -years race residence 6 0 52 Parity Distribution of tumour 3.3 1 7 menopausal status religion 6.4 marital status educational level weight age at menarche exact parity oral histologies similar for exposed and unexposed cases potential for talc exposure by way of contraceptives pelvic surgery or perineal hygiene considered no information contraceptive use on duration or frequency of postmenopausal talc use low participation use of hormones rates among controls 56 TALC tobacco smoking of cases matched with no refusals 27 matched after 1 refusal % matched after 2 or more refusals Hartge et al 1983 Washington DC USA 1974-77 135 incident cases Interviews to collect Any use of 67 treated at participating information on reproductive talc hospitals and sexual history medical Genital 7 171 population history drug use and other exposure to controls frequency- exposures exposure to talc talc matched by age race categorized as any or hospital genital includes use on genitals on sanitary napkins or on underwear 0.7 0.4 2.5 0.7 1) Age race pregnancy 10.0 Questions on talc added after study began no information on duration or frequency of exposure no controlling for other potential confounders potential for selection bias 343 344 Table 2.3 contd Reference study location study period Characteristics of cases Exposure assessment and controls Exposure categories No of Odds ratio exposed 95 CI cases Adjustment for potential confounders Comments IARC Whittemore et 188 incident cases Structured person Type of al 1988 diagnosed at interviews information application San Francisco 8 hospitals aged 18 74collected on medical history Perineum only 22 CA USA 1983 years histological menstrual and reproductive Sanitary pads 5 85 verification of history family history only diagnosis 539 controls selected from women environmental exposures talc coffee alcohol tobacco talc exposure Diaphragm only 9 Any two 67 All three 1 hospitalized for non- categorized by type of 1.5 08-26 0.6 2 Parity oral 1contraceptive use 1.5 0 6 63 1.4 0.9 2.0 0.4 0.0-29 0.0-29 No trend of increasing risk with increasing duration of exposure as measured in years of talcum powder use on the perineum prior to tubal ligation or hysterectomy statistically significant cancerous conditions 280 or from the population using random dialling 259 matched by age -years race application duration of use prior to tubal ligation or hysterectomy frequency of use Duration of use years None 103 1-9 34 10 50 Parity 1.0 1 6 1.0 2.6 1 0.7 17 MONGRAPHS trend ofincreasing risk with increasing frequency of exposure as measured in number of applications of talc to the perineum per month VOLUME hospital of Parity Frequency ofuse admission hospital Never 97 10 controls or telephone 1-20 41 3 0.8 02 area prefix month population controls 93 20 month 44 15 09-2.2 09-2.2 30 month = - 3 9 1.9 p for trend 19 co2n.3 ctondtd Reference study location study period Characteristics of cases Exposure assessment and controls Exposure categories No. of Odds ratio exposed 95 CI cases Adjustment for potential confounders Comments Booth et al 1989 London and Oxford United Kingdom 1978-83 235 incident cases from 15 hospitals aged 65 years or under at diagnosis diagnosed within 2 years of interview histological confirmation of diagnosis 451 hospital controls selected from Interviewer- administered standard questionnaire information obtained on reproductive and menstrual history on exposure to exogenous estrogens cigarettes talc talc exposure categorized by frequency of use on perineum and whether it was used to store a Frequency of use Never 76 Rarely 6 Monthly 7 Weekly 57 Daily 71 p for trend Age 1.0 socioeconomic 0.9 0 3 '2status 0.7 0 3 1.8 20 1.3 31.43 34 1 3 0 8 19 0.05 Participation rates not p_rovided questions on talc use added 3 months after start ofstudy data on talc exposure missing for 18 cases and 17 controls same 15 hospitals same age distribution diaphragm as the cases TALC Harlow & Weiss 1989 116 Caucasian women from 3 urban counties person interviews information obtained on Any perineal 49 use 7 2.1Age parity use Cases diagnosed with western captured in Seattle- reproductive sexual and of oral borderline serous or Washington State USA 1980-85 Puget Sound Cancer Surveillance System medical histories as well as perineal exposure to talc talc Type ofpowder used aged 20-79 years independent pathological review 73 of total exposure categorized as any Cornstarch only 4 perineal use by method of Baby powder 18 use and by type of powder only used Baby powder 22 histological agreement combined contraceptives 08 08 0 2 83 08 08 0.4 1.9 9 0 5 250 20 mucinous tumours study limited by incomplete information on powder use and small size no significant association between method ofpowder use and risk for borderline 94 of reviewed cases 158 white population- based controls selected by random dialling matched by Talc unspecified 13 Deodorizing 10 powder only Deodorizing 14 combined 04 5(2 2 278 2 1 117 tumours age county of residence 345 346 Table 2.3 contd Reference study location study period Characteristics of cases Exposure assessment and controls Exposure categories No. of | Odds ratio exposed 95 CI cases Adjustment for potential confounders Comments Chen et al 1992 112 women from Beijing Cancer administered questionnaire information Use on perineum 7 or lower 3.9 09 106Education parity Age range of cases and Beijing China 1984-86 Registry with mean age 4848 5 years confirmation of obtained on menstrual obstetric marital medical family and dietary histories as abdomen controls not reported IARC diagnosis by well as exposure to talc laparotomy and perineally and pathological occupationally perineal MONGRAPHS examination in all cases 224 population controls selected first on basis of area of exposure reported as yes residence of cases and VOLUME then randomly from census lists ofall women within | year ofage of identified case matched by age 93 mean age 49 0 years Table 2.3 contd Reference study location study period Characteristics of cases Exposure assessment and controls Exposure categories No of Odds ratio exposed 95 CI cases Adjustment for potential confounders Comments Harlow et al 1992 235 white women from person interviews 10 hospitals in information collected on Any perineal 114 use of talc Boston MA metropolitan Boston occupational history medical Method of Massachusetts area aged 18 7y6ears and reproductive history application USA 1984 87 independent dietary history tobacco Sanitary napkins 9 pathological smoking hygienic practices or underwear hysterectomy confirmation of including perineal exposure to only diagnosis talc exposure to talc Partner or 20 239 population categorized by type of applications to controls randomly selected from town application brand of powders duration and diaphragm Dusting on 85 registers matched by _ age -years race precinct of residence frequency of use perineum Frequency no per month no history of bilateral TALC oopherectomy None 121 < 32 5-29 24 1.0 0.4 2.1Parity education marital status religion use of 82 sanitary napkins Odds ratio for women with 10 000 lifetime applications unchanged after excluding applications that occurred after tubal 2 0.6 douching age weight 24 ligation or odds ratio 17 17 95 CI 1.0 03 significant increase in odds ratio for 7 1.1 72 women with 10 000 lifetime applications observed after excluding use of talc during non- 10 1 5 0.8 72 1 2 0.6 2.2 ovulatory periods and after surgical sterilization odds ratio 2 8 95 CI 1 4 45 30 58 8 1 1 3 p for trend 0 046 Years ofuse None 121 10 10 10-29 30 p for trend 14 1 2 0 5 265 26 49 6 0-2 51 1 6 1 0 72 007 Total applications None 121 10 1000 1000-10000 1000-10000 10 000 p for trend 18 37 2 54 5 0 9 294 24 42 8 0 30 0.09 347 348 Table 2.3 contd Reference study location study period Characteristics of cases Exposure assessment and controls Exposure categories No of Odds ratio exposed 95 CI cases Adjustment for potential confounders Comments Rosenblatt et al 1992 Baltimore MD USA 1981-85 77 women admitted to Questionnaire administered Johns Hopkins by telephone and in the Hospital as patients hospital information for treatment or collected on genital and diagnosis diagnosed respiratory exposure to fibre- within 6 months of containing substances such admission residents of _ as talc sources of genital the USA pathological exposure included Genital fibre use 67 Method of application Diaphragm use 14 with powder Genital bath talc 22 Sanitary napk~-n 22 with talc confirmation of diagnosis 46 hospital contraceptive methods diaphragm condoms dusting of perineum and exposure controls selected from sanitary products sources of female patients with respiratory exposure no gynaecological or included use of face and malignant conditions matched a posteriori by age -years race closest date of diagnostic admission body powders residential or occupational exposure to containing substances such as talc asbestos fiberglass estimation of dose by adding number of years of exposure from all sources 2 P4 arity Investigators encountered difficulty finding controls who met all of the JARC 0 8 108Parity education matching criteria For No adjustment analysis 46 matched sets 7 H3 ighest weight of which 31 sets had 2 MONGRAPHS 43 171 year prior to diagnosis cases and I control limitations include small study size broad definition of fibre exposure limited information available on perineal exposure to talc VOLUME 93 Table 2.3 contd Reference study location study period Characteristics of cases Exposure assessment and controls Exposure categories No of Odds ratio exposed 95 CI cases Adjustment for 'Comments potential confounders Tzonou et al 189 women Questionnaire administered in Talc application 1993 hospitalized for hospital by medical residents in perineum Athens Greece ovarian cancer surgery information collected on No 183 1989-91 in 2 major cancer medical and reproductive Yes 6 hospitals in Greater histories as well as personal Athens aged 75 years demographic and under histological confirmation of diagnosis socioeconomic variables qualitative assessment oftalc exposure yes use in the 200 hospital visitor perineal region controls selected from visitors to patients hospitalized in the same wards as cases not matched to cases by age Age education Study limited by very low weight age at prevalence of perineal talc 1.0 menarche use 1 3 4.0menopausal status age at menopause parity age at first birth smoking status TALC alcohol use coffee consumption use of analgesics use of tranquilizers or hypnotics use of hair dyes 349 Table 2.3 contd 350 Reference study location study period Characteristics of cases Exposure assessment and controls Exposure categories No. of Odds ratio exposed 95 CI cases Adjustment for potential confounders Comments Purdie et al 1995 Queensland 824 incident cases diagnosed and registered in all major administered standardized questionnaire ^fin clinic cases or home some Use of talc around the abdomen or 467 1.3 1.0-15 Parity other 56.7 potential New South gynaecological- Wales Victoria oncology treatment cases all controls information collected on perineum confounders e g contraceptive Australia 1990- 93 centres in 3 states aged 18-79 years independent medical reproductive family and occupational histories as well as dietary factors and use also considered IARC pathological history of talc use confirmation of diagnosis MONGRAPHS 860 population controls selected randomly from electoral rolls stratified by age and geographical region Shushan et al 1996 Israel 1990-93 200 incident cases 164 invasive 36 borderline diagnosed administered standard questionnaire information collected on Use of talc Moderate lot 21 and reported to Israel Cancer Registry aged reproductive history use of oral contraceptives and 36-64 years fertility drugs exposure to histological talc exposure to talc stratified confirmation of into seldom diagnosis moderate lot 408 population controls selected by random dialing matched by geographical area 197 197 p = 004 004 VOLUME No control for confounding Study limited by the very sparse information on talc use and the unavailability 93 of adjusted results for the association between use of talc and the risk for ovarian cancer Table 2.3 contd Reference study location study period Characteristics of cases Exposure assessment and controls Exposure categories No. of Odds ratio exposed 95 CI cases Adjustment for =Comments potential confounders Chang & Risch 1997 450 incident cases primary invasive and administered questionnaire information Any exposure 198 to talc metropolitan Toronto and _ southern of Ontario Canada 1989- 92 borderline aged 35 79 years histological confirmation of diagnosis 564 population controls identified through provincial collected on menstrual and reproductive history use of hormones and oral contraceptives and use of talc exposure to talc categorized on basis of any exposure type of exposure Type of exposure Sanitary napkins 51 After bathing 172 Frequency of after use month None records of all frequency and duration of 10 76 homeowners tenants perineal application 10-25 54 of TALC and family members 25 41 randomly selected Per 10 from same residential area matched by age applications per month within year age Duration of groups after use 1 A1ge interview Authors do not specify duration of oral whether cases were 1.3 9 0 contraceptive 20use parity n1umber full- term pregnancies duration of 1.0 lactation per 2 p2regnancy 7 h1 istory tubal 0 0.6 1ligation or 09 7 11) hysterectomy identified through a cancer registry or some other reporting mechanism Borderline significant trend observed with increasing duration ofexposure to talc but not with increasing frequency ofexposure family history of breast or ovarian cancer years None 30 60 30-40 71 40 41 Per 10 years of use 1.0 1 1.1 41 0 005 110 26 2 14 1.2 351 352 Table 2.3 contd Reference study location study period Characteristics of cases Exposure assessment a_nd controls Exposure categories No of Odds ratio exposed 95 CI cases Adjustment for potential confounders Comments IARC Cook et al 1997 Western Washington State USA 1986-1988 313 incident cases 234 invasive 79 borderline identified from records of Cancer Surveillance System ofwestern Structured person interviews information collected on medical and reproductive histories smoking habits birth control methods and use of genital Lifetime perineal application None 154 Any 159 Exclusive use of powder for Adjusted for age 10 51 1 2.0 Adjusted for age Washington white residents of three powders and deodorant sprays exposure to genital Perineal dusting 55 Diaphragm 32 counties King Pierce powders assessed on the basis storage 18 12 29 0.8 0 4 14 Snohomish aged 20- of any of anylifetime exposure Dusting sanitary 12 79 years no method of use and cumulative napkins information on whether lifetime exposure days Deodorant spray 18 MONGRAPHS diagnosiswas months or lifetime Any use of histologically applications powder for confirmed VOLUME 422 white population- based controls selected Perineal dusting 95 Diaphragm 46 storage 5 6 3.6 58 Adjusted for age 3and other methods of 61 10 06 genital powder 2application 16 VOLUME by random digit- Dusting sanitary 38 0 0.5 51 dialling part of a larger control pool for napkins Adjusted for age 93 several studies of Deodorant spray 40 1.1-31 and other Cumulative cancer in women methods of matched by age lifetime perineal genital powder dusting days application None 154 10 /2000 2001-5000 5001 10000 10 000 20 8 0.9 53 24 16 09 29 21 2 0 6 2.4 28 8 0.9 43 Table 2.3 contd Reference study location study period Characteristics of cases Exposure assessment and controls Exposure categories No of Odds ratio exposed 95 CI cases Adjustment for potential confounders Comments Eltabbakh et al 1998 Buffalo NY USA 1982-96 Study group 50 women admitted for treatment of primary ovarian administered item questionnaire completed at hospital admission peritoneal cancer to Roswell Park Cancer Institute histological confirmation of diagnosis control group 466 women treated for primary ovarian cancer at same centre pathological review of diagnosis Perineal use of talc 224 = 003 48 % No control for confounding Cases for this study were women diagnosed with primary peritoneal cancers Case definition excluded patients with diagnoses of peritoneal mesothelioma borderline tumours of peritoneum or invasive TALC ovarian cancer no healthy controls enrolled in this study Controls were women diagnosed with primary epithelial ovarian cancer Control definition excluded patients with diagnoses of epithelial ovarian cancer and ovarian cancer secondary to metastases from other sites 53 354 Table 2.3 contd Reference study location study period Characteristics of cases Exposure assessment and controls No of Odds ratio exposed 95 CI cases Adjustment for potential confounders Comments IARC Godard et al 1998 Montreal 170 incident cases with primary invasive or borderline epithelial Standardized item questionnaire telephone or person interviews Ever use oftalc 18 25 09-66 10 % Age at menarche age at Quebec tumours identified at conducted with cases no menopause Canada 1995- 96 two gynaecological clinics aged 20 84 years histological confirmation of diagnosis 170 population controls selected by a information on how controls were interviewed qualitative assessment ofperineal tale exposure never parity age at first and last childbirth duration oforal contraceptive use age at last oral MONGRAPHS modified random dialling method frequency by contraceptive VOLUME use tubal ligation alcohol age -year French Canadian ethnicity VOLUME use previous breast or abdominal 93 surgery Table 2.3 contd Reference study location study period Characteristics of cases Exposure assessment _and controls Exposure categories No of Odds ratio exposed 95 CI cases Adjustment for potential confounders Comments Cramer et al 563 incident cases person interviews using No genital 411 1999 including borderline standardized questionnaire exposure eastern tumours identified information collected on Any genital 152 Massachusetts through hospital medical and reproductive exposure and New tumour boards or histories family history and Methodof use Hampshire statewide cancer personal habits multiple No use 312 USA 1992 97 registries age range questions on potential routes genital 99 not provided of talc exposure genital areas histological genital husband's use Dusting 71 confirmation of brands used age at first use perineum 10 Age study site 6( 2 parity oral 2contraceptive use body mass index family 10 history of breast 1 8 1.5or ovarian 1.5 0 cancer history of 2tubal ligation TALC diagnosis for all cases duration and frequency of use Dusting sanitary 20 523 population napkins controls selected by random dialling and through annual Dusting 8 underwear More than one 53 listings of names ages and addressesof all method Frequency 57 3 2 4 3.6 2 1 3-3.6 Massachusetts residents women over the age of 60 years frequency by age 4 years location of residence month None 312 30 64 30-39 59 40 23 Duration ofuse 1.0 2.2 1.4 63 7 0.8 81 7 0.8 )3 years None 312 10 20 20-30 30 55 19 1 2 30 32 1.3 0 8 32 59 1,4 0 9 32 355 356 Table 2.3 contd Reference study location study period Characteristics of cases Exposure assessment a_nd controls Cramer et al 1999 contd Exposure categories No of Odds ratio exposed 95 CI cases Adjustment for potential confounders Comments Total no of applications None 312 10 3000 3000 10000 10 000 for trend Total no of applications 51 1.8 1.1 03 36 1 4 0.8 204.8 24 59 4 0 9 22 0.16 censored analysis None 312 1.0 3000 3000 10000 10 000 p for trend 59 5 10 2.4 10 2.4 51 7 1 1 82 36 1 0 23 0.02 0.02 IARC MONGRAPHS Censored analysis excludes talc applications that occurred during non- VOLUME ovulatory years or after hysterectomy or tubal ligation Includes non- genitally exposed women VOLUME 93 Table 2.3 contd Reference study location study period Characteristics of cases Exposure assessment and controls Exposure categories No of Odds ratio exposed 95 CI cases Adjustment for potential confounders Comments Wong et al 462 incident cases administered item Method of use Age parity oral Case population largely 1999 Buffalo NY admitted for treatment ofprimary extra- questionnaire completed at hospital admission Never 241 Sanitary napkin 13 10 contraceptive 4-2 use smoking that reported by Eltabbakh al 1998 32 cases USA 1982 92 ovarian peritoneal cancer to Roswell Park information collected on medical social family Genital or thigh = 157 area 0 0 8 13 family history of 39 controls did not recall ovarian cancer duration of use Cancer Institute mean dietary and occupational Both 51 7 1.7age at menarche age 54 9 years histories method of talc use = Duration of use menopausal histological never sanitary napk~-n years status income TALC confirmation of diagnosis 693 hospital genital area both assessed and duration of use None 1-9 10-19 241 10 education 39 6 g1 eographical 49 0.9-2 2 location history controls treated for 20 101 06-1.2 of tubal ligation gynaecological or hysterectomy malignancies at same cancer centre mean age 54 9 years frequency to cases by age at diagnosis -years 357 358 Table 2.3 contd Reference study location study period Characteristics of cases Exposure assessment and controls Exposure categories No of Odds ratio exposed 95 CI cases Adjustment for potential confounders Comments Ness al 767 incident cases Standardized person Method of use Age parity race Risk for ovarian cancer JARC 2000 identified at 39 interviews information Never 349 eastern hospitals in the collected on sexual activity Feet arms 335 Pennsylvania Delaware Valley use of contraceptives breasts southern New region aged 20 69 menstrual and reproductive Genital 161 10 family history of 1.1-1 ovarian cancers oral 2 2.0contraceptive compared with 50 women with primary peritoneal cancers no control for confounding analysis of MONGRAPHS Jersey diagnosis within 6 history and history and Sanitary napkin 77 Delaware USA months prior to duration oftalc use genital 'Underwear 70 1994-1998 interview pathological genital applications Diaphragm 10 review of a random exposure via male sexual cervical cap subset of cases n = partners Male partner 56 120 Duration ofuse 61 712 0.6 3 007 2.3_ use tubal 2.4 ligation 1.2hysterectomy lactation 1.4 duration examined risk for cases reporting of use talc on the feet genital and rectal areas 1367 population years controls identified Never 401 10 VOLUME through random digit dialing /6y5ears of age and Health Care < 17 2.0 1 0 4.0 1-4 76 6 1 1 2.3 5-9 40 1.2 0 8 198 19 Financing 10 233 2 0 1.5 93 Administration lists 65-69 years ofage frequency matched by age and location of residence Table 2.3 contd Reference study location study period Characteristics of cases Exposure assessment and controls Exposure categories No of Odds ratio exposed 95 CI cases Adjustment for potential confounders Comments Langseth & Kjaerheim 35 invasive and borderline tumours person interviews conducted at mills or by Ever of use talc 12 for personal 2004 selected from cohort of telephone information hygiene Norway 1953- 4247 female pulp and collected on occupational 99 paper workers cohort history household exposure follow 1953 99 to asbestos menstrual and histological review and reproductive history confirmation of hereditary risk of cancer as diagnosis well as talc use on sanitary 121 selected from the napkins underwear or diapers cohort by incidence or by husband in genital area density sampling matched by birth year 2 years controls had no ovarian cancer and had intact ovaries 24 2 3Adjusted for possible Nested control study conducted in a cohort study confounders but of 10 pulp and paper mills not explicitly many missing values stated among proxy respondents TALC 359 360 Table 2.3 contd Reference study location study period Characteristics of cases Exposure assessment and controls Exposure categories No. of Odds ratio exposed 95 CI cases Adjustment for potential confounders 'Comments Mills et al 249 incident cases Telephone interview to obtain Perineal use of Age Cumulative use calculated 2004 from 22 counties information on medical talc ethnicity as frequency categorical central diagnosed in two history menstrual and Never 143 10 duration of oral = weighting from 0 3 California regional cancer reproductive history family | Ever 106 1.4 0 19contraceptive multiplied by duration USA 2000-01 registries using rapid ~ hsistory of cancer history Frequency of use case ascertainment perineal talc exposure Never 143 10 use breastfeeding IARC procedures frequency duration and week 34 3 0.9 2Additional histological confirmation of calendar years of use cumulative use calculated week week 31 0 7-18 covariates 41 7 1 2considered to be MONGRAPHS diagnosis subset of cases 1105 population controls identified by random dialling by multiplying frequency categorical variable by duration in months p for trend Duration of use years Never 143 /3 18 0015 1.0 0 0.6 potential confounders included family history of breast 1or ovarian VOLUME frequency by age race ethnicity 4 12 13-30 32 1.2 30cancer parity 29 1.5 0.9 2.3_ history of VOLUME 30 p for trend 21 2 0.7 )2 pregnancy body 0 045 mass index Cumulative use hysterectomy 93 Never 143 1.0 tubal ligation 1st quartile 18 1.0 0.6 81 duration of post- lowest 2nd quartile menopausal use 28 18 1 30 of hormones 3rd quartile 34 7 1 27 4th quartile 20 1 1 0.6 180.6 18 highest p for trend 051 CI confidence interval TALC 361 to talc by way of contraceptives perineal hygiene or surgery Ninety cases 42.8 and 61 controls 28.4 reported a history of regular use of talc as a dusting powder to the perineum on sanitary napkins or on both After adjustment for parity yes and menopausal status post- a significant association was found between any perineal use of talcum powder and the risk for ovarian cancer odds ratio 1.9 95 CI 1.3 2.9 This association was attenuated but still significant after adjustment for additional potential confounders including religion marital status level of education weight age at menarche parity number of children oral contraceptive use menopausal use of hormones and tobacco smoking adjusted odds ratio 1.6 95 CI 1.0 2.A5 single type of perineal exposure to talc either as a dusting powder to the perineum or on sanitary napkins was associated with a borderline significantly increased risk for ovarian cancer odds ratio 1.6 95 CI 1.0 2.a5fter adjustment for parity and menopausal status while a history of both types of perineal exposure was associated with a significant increase in risk adjusted odds ratio 3.3 95 CI 1.7-6.4 No association was seen between other potential sources of exposure to talc pelvic surgery use of condoms use of diaphragm or using tale for diaphragm storage and the risk for ovarian cancer In addition the results were essentially unchanged after excluding women who had had a tubal ligation or hysterectomy odds ratio 2.8 P < 0.003 although the authors noted that these surgical procedures are usually performed at mid when substantial exposure to talc may already have occurred The distribution of tumour histologies was similar for exposed and unexposed cases 53.7 of tumours were classified as serous among the unexposed cases and 48.9 among the exposed cases with any perineal use of talc Limitations of this report include the lack of information on duration and frequency of talc use In addition participation rates among the controls were quite low 50 although the authors noted in a secondary analysis that when cases were matched to the first control selected i.e. 100 participation a positive association was also found odds ratio 2.44 P < 0.05 Hartge et al 1983 published a brief report of a study conducted between 1974 and 1977 in the Washington DC USA area The study included 197 cases treated for pathologically confirmed epithelial ovarian cancer at participating hospitals and 197 controls treated at the same hospitals for conditions other than pregnancy malignancies and gynaecological or psychiatric diseases Controls were frequencymatched to cases by age race and hospital Interviews were conducted in the hospital for controls and at home for most cases to collect information on reproductive and sexual history medical history drug use and other exposures Questions on exposure to tale were added after the study began As a result the analysis included only 135 cases and 171 controls with information on exposure to talc seven cases 49.6 and 100 controls 58.5 reported any use of talc including genital uses while seven cases 5.2 and three controls 1.8 reported genital use of talc including use on genitals on sanitary napkins or on underwear No association was observed between any use of talc and the risk for ovarian cancer odds ratio 0.7 95 CI 0.4-1.1 This estimate was unchanged after adjustment for race age and pregnancy A significant positive association was found between genital use of talc and the risk for ovarian cancer odds 362 IARC MONOGRAPHS VOLUME 93 ratio 2.5 95 CI 0.7 10.L0imitations of this study included its small size and the low prevalence of genital use of talc the lack of information on its duration and frequency and age at first use the lack of control for other potential confounders and the increased potential for selection bias due to different interviewing protocols for cases and controls In addition no information was given in this brief report on the methods used in the analysis to control for confounding] Whittemore et al 1988 analysed the association between perineal use of talc and the risk for invasive epithelial ovarian cancer among 188 cases and 539 controls in the San Francisco Bay area CA USA Cases were residents of northern California aged 1874 years who had been diagnosed with an invasive ovarian tumour between January 1983 and December 1985 at one of eight hospitals Controls were either selected from among women who had been hospitalized for a cancerous condition at one of these eight hospitals or were identified from the population using random dialling Women in each control group were matched to each case by age within 5 years and race white black other plus hospital and date of admission within 3 months for the hospital controls n = 280 and telephone area code and prefix for the population controls n = 259 Structured interviews were conducted in the homes of participants to obtain information on the history frequency and duration of perineal use of talc medical history and additional covariates of interest menstrual and reproductive histories family history and environmental exposures such as consumption of alcohol coffee and tobacco Of 317 eligible cases eight 2.5 were excluded due to physician refusal 30 9.5 due to patient refusal 44 13.9 due to death or incapacitating illness and 47 14.8 due to invasive tumours which left 188 59.3 for inclusion in the analysis Among the controls 68 of the women identified as eligible hospital controls n = 354 and 71 of the women identified by telephone as eligible population controls n = 329 agreed to participate After excluding controls matched to cases with bordeline tumours 280 hospital controls and 259 population controls were included in the analysis Wu et al 1988 Exposure to talc was categorized by type of application perineum only sanitary pads only diaphragm only any two types of application or all three types of application duration of use before tubal ligation none 1-9 years 10 years unknown and frequency of use none 1-20 applications per month > 20 applications per month unknown Conditional logistic regression was used to calculate the odds ratio for each exposure and to test for trend Ninety cases 51.6 and 247 controls 45.8 reported previous use of talcum powder on the perineum to yield an odds ratio of 1.40 P = 0.06 after adjustment for parity Since the odds ratios were similar when hospital and population controls were analysed separately analyses using the combined group of controls were reported After adjustment for parity and oral contraceptive use the odds ratio for use of talc on the perineum only was 1.5 95 CI 0.8-2.6 No significant associations were observed with either individual or multiple types of perineal talc use including the combination of use on the perineum sanitary napkins and a diaphragm odds ratio 1.4 95 CI 0.9 2.f0or any two types of use versus 0.4 95 CI 0.0 2.9for all three types combined No TALC 363 significant trend was observed with duration of talc use on the perineum before tubal ligation or hysterectomy Odds ratios were 1.6 95 CI 1.0-2.6 for 1-9 years of exposure and 1.1 95 CI 0.7-1.7 for more than 10 years of exposure A significant trend of increased risk with increasing frequency of perineal use of talc was observed with an overall odds ratio of 1.3 95 CI 0.9-1.9 P = 0.19 for 30 applications per month When stratified by history of perineal use of talc yes and history of tubal ligation or hysterectomy yes women who had used talc perineally and but had not undergone surgery for sterilization had the highest risk for ovarian cancer odds ratio 1.3 95 CI 0.9-2.0 Limitations of this study included the lack of information on talc use] Booth et al 1989 reported results of a hospital control study of the risk for ovarian cancer conducted in 15 hospitals in London and Oxford United Kingdom from October 1978 to February 1983. Women aged 65 years or under at diagnosis and who were diagnosed within 2 years of the study interview were eligible for inclusion A total of 280 potential cases were identified interviewed and classified with respect to tumour histology After excluding 45 women 235 cases were included in the analysis A total of 451 controls with the same age distribution as the cases were selected from the same 15 hospitals Controls had a range of admission diagnoses gastrointestinal disease n 105 and bone or joint disease n 70 were the most common Women were excluded as controls if they had a history of bilateral oophorectomy or if they had a condition related to oral contraceptive use or other reproductive factors Participation rates were not provided Interviewers used a standard questionnaire to obtain information on reproductive and menstrual history as well as exposure to exogenous estrogens cigarettes and talc Talc exposure was categorized according to the frequency of perineal use never rarely monthly weekly or daily and whether it was used for storage of a diaphragm Multiple logistic regression adjusted for age and socioeconomic status was conducted seven cases 24.3 and 77 controls 17.1 reported a history of weekly use of talc in the genital area while 71 cases 30.2 and 139 controls 30.8 reported daily use Weekly genital use of talc was associated with a significantly increased risk for ovarian cancer odds ratio 2.0 95 CI 1.3-3.4 while daily use was associated with a significant increase in risk odds ratio 1.3 95 CI 0.8-1.9 after adjustment for age and socioeconomic status The value for trend with increasing frequency of use was of borderline significance P 0.05 The percentage of diaphragm users who reported storing their diaphragm in tale was not significantly different between the cases 86 and controls 81 Limitations of this hospital study included the limited information on talc use As participation rates were not provided the possibility of selection bias is difficult to evaluate Although covariates such as oral contraceptive use or parity were available it was not explicitly stated if they were evaluated Harlow and Weiss 1989 conducted a study of perineal use of powder and the risk for borderline ovarian cancer in western Washington State USA Cases were 116 Caucasian women aged 20-79 years who had been diagnosed with borderline serous or mucinous epithelial ovarian cancer between 1980 and 1985 and who were identified by International Classification of Diseases codes obtained from a population 364 IARC MONOGRAPHS VOLUME 93 reporting system Controls were identified from the same counties of residence by random dialling A total of 158 women with a similar age distribution to the cases and who had not undergone a bilateral oophorectomy were included in the analysis Cases and controls were interviewed person to obtain information on reproductive sexual and medical histories as well as on perineal exposure to talc through multiple openended questions about the history of powder use of the participant Among all eligible cases and controls identified for the study 68 of the cases and 74 of the controls were interviewed The authors controlled for age 20-39 40-59 or 60-79 years parity nulliparous or parous and oral contraceptive use never Exposure to tale was broadly categorized as any perineal use of dusting powders after bathing on sanitary napkins or for diaphragm storage and further subcategorized according to method of use diaphragm storage only after bathing only sanitary napkins only after bathing and on sanitary napkins and specific combinations of the various methods and type of powder used cornstarch only baby powder only talc unspecified no combined use deodorizing powder only or combinations of powders Forty cases 42.2 and 64 controls 40.5 reported a history of any perineal exposure to powder to yield an odds ratio of 1.1 95 CI 0.7 2.W1hen analysed by the type of powder used the risk for borderline ovarian cancer was elevated only for perineal use of deodorizing powder alone odds ratio 3.5 95 CI 1.2-28.7 or in combination with other powders odds ratio 2.8 95 CI 1.1 11.N7 o association was noted for the use of baby powder alone odds ratio 0.8 95 CI 0.4-1.9 or for combined use odds ratio 0.9 95 CI 0.5-2.0 or for other unspecified use of talc odds ratio 1.0 95 CI 0.4-2.4 No significant association was found between risk for borderline tumours and any individual method of powder use including use after bathing on sanitary napkins or for diaphragm storage The authors reported no increase in risk with increasing number of days of powder use although the data were not provided in the paper Limitations of this study included the incomplete information on powder use and its small size] Chen et al 1992 described in detail in Section 2.1.2 conducted a control study in Beijing China of several risk factors for epithelial ovarian cancer that included perineal exposure to talc yes use of dusting powder to the lower abdomen or perineum for 3 or more months The analysis was carried out on 112 newly diagnosed cases identified between 1984 and 1986 through the Beijing Cancer Registry and 224 matched community controls two controls per case Seven cases 6.3 and five controls 2.2 reported use of containing powders which resulted in an odds ratio of 3.9 95 CI 0.9-10.6 after adjustment for education and parity The Working Group noted the incomplete ascertainment of cases of ovarian cancer due to the nature of the reporting system in China the large number of cases that were excluded due to death and the exclusion of controls who had a history of serious health problems which may have resulted in selection bias the limited information on perineal use of talc the lack of adjustment for other potential confounding variables the small number of cases and the low prevalence of talc use TALC 365 Harlow et al 1992 analysed perineal exposure to talc and the risk for ovarian cancer among 235 cases and 239 controls in the Boston MA metropolitan area USA Cases were diagnosed with ovarian cancer between June 1984 and September 1987 at one of 10 Boston hospitals and controls were identified from town registers listing the name age and address of all residents in Massachusetts All cases were Caucasian women aged 18 76 years at diagnosis and were similar to the controls with respect to race age and area of residence Of 397 cases identified during the study period % were not interviewed due to physician and patient refusal death or change of address After excluding women whose cancer diagnosis was not confirmed by an independent pathology review 9.4 of eligible cases 235 women were included in the analysis A total of 526 women were contacted as potential controls Of these 239 45.4 were interviewed 25 could not be reached % reported a previous bilateral oophorectomy and % did not wish to participate in the study person interviews were conducted with cases and controls to obtain information on occupational history medical and reproductive histories dietary history cigarette smoking and hygienic practices use of douches types of sanitary protection used perineal exposure to talc Exposure to talc was categorized on the basis of any exposure the method of application dusting on sanitary napkins and underwear via partner or application to diaphragm dusting on perineum the brand used age at first use duration and frequency of use Total lifetime exposure to talc was estimated by cumulating the frequency of exposure and years of use to arrive at a summary measure of the total number of applications < 1000 1000-10 000 > 10 000 Covariates evaluated as potential confounders included age education marital status religion weight use of oral contraceptives and parity of these age education < 12 years > 12 years marital status never religion Jewish Jewish weight < 140 lb 140 lb and parity 0 1-2 > 2 were included in all multivariable models A history of any perineal exposure to containing powders was reported by 48.5 of cases and 39.3 of controls to yield an odds ratio of 1.5 95 CI 1.0-2.1 When the method of application was examined only direct application to the perineum as a dusting powder was associated with a significant increase in risk odds ratio 1.7 95 CI 1.12.7 Women who reported at least 30 applications of talcum powder per month had a significant increase in risk odds ratio 1.8 95 CI 1.1-3.0 while women with fewer applications per month did not A significant positive trend was seen with number of monthly applications P = 0.046 Women with at least 10 years of perineal exposure had a borderline significant increase in risk odds ratio 1.6 95 CI 1.0-2.7 and the value for trend was also of borderline significance P = 0.07 Analyses stratified by age at first use indicated that women who first used talc genitally before the age of 20 years had the highest risk odds ratio 1.7 95 CI 1.1-2.7 those stratified by years since last use suggested that women with the most recent perineal use of talc within the previous 6 months had the highest risk odds ratio 2.3 95 CI 1.3-4.0 In an analysis stratified by use before versus after 1960 women who reported some perineal use of talc before 1960 had a significantly elevated risk for ovarian cancer odds ratio 1.7 95 CI 1.1 2.7 while women with exclusive genital use of talc after 1960 did not odds ratio 1.1 366 IARC MONOGRAPHS VOLUME 93 95 CI 0.6 2.W1 omen who had used more than 10 000 lifetime applications had a borderline significant increase in risk odds ratio 1.8 95 CI 1.0-3.0 This was unchanged after excluding applications that occurred after tubal ligation or hysterectomy odds ratio 1.7 95 CI 1.0 3.0However when use of talc during ovulatory periods and after surgical sterilization was excluded the increase in risk associated with more than 10 000 lifetime applications was significant odds ratio 2.8 95 CI 1.4 5.4 In analyses of each histological type and grade the strongest associations were seen for endometrioid tumours odds ratio 2.8 95 CI 1.2-6.4 and tumours of borderline invasiveness odds ratio 2.4 95 CI 1.2-4.5 Table 2.4 Rosenblatt et al 1992 conducted a hospital control study among 77 women who were hospitalized at Johns Hopkins Hospital in Baltimore MD USA for ovarian cancer cases and 46 who were hospitalized for gynaecological nonmalignant conditions controls The cases were newly diagnosed with pathologically confirmed epithelial ovarian cancer between 1981 and 1985 the majority of whom were aged 40-69 years Of 140 eligible cases 108 77.1 were interviewed Thirteen were subsequently excluded because no control was identified and 18 were excluded for an unspecified reason Controls were matched to cases by age race and date of diagnostic admission Information on genital and respiratory exposure to containing substances talc asbestos and fibreglass as well as potential confounders was collected using a structured questionnaire which was administered in the hospital and by telephone Covariates that were considered to be potential confounders included tobacco use ovulatory time period parity family history of cancer obesity education education of husband previous history of cancer marital status religion and the use of oral contraceptives and other methods of contraception Sources of genital fibre exposure yes included diaphragm use and dusting of either the perineum or sanitary napkins with talcum powder Potential sources of respiratory fibre exposure yes included use of face or body powders containing talc insulation installed at residence and living in the vicinity of or employment in a emitting industry such as shipyard asbestos or tale mine fibreglass processing plant A large percentage of both the cases 87 and controls 88 reported exposure to genital fibre with an odds ratio of 1.0 95 CI 0.2-4.0 after adjustment for parity A long duration of genital fibre use median duration 37.4 37.y4 ears was associated with a borderline significant increase in the risk for ovarian cancer odds ratio 2.4 95 CI 1.0-5.8 after adjustment for religion Odds ratios were also calculated for genital use of bath talc odds ratio 1.7 95 CI 0.7-3.9 use of talc on sanitary napkins odds ratio 4.8 95 CI 1.3-17.8 and use of talc on a diaphragm odds ratio 3.0 95 CI 0.8-10.8 No association was observed between risk for ovarian cancer and history of previous gynaecological or abdominal surgery that may have resulted in peritoneal exposure to talc Limitations of this study included the very small number of cases and controls the broad definition of fibre exposure used in certain exposure variables and the limited information on perineal exposure to talc] Tzonou et al 1993 conducted a hospital control study of risk factors for epithelial ovarian cancer in the Greater Athens region of Greece The cases were 189 women Table 2.4 Perineal talc use and ovarian cancer risk by tumour histology References No. of cases Histology Relative riska 95 CI Harlow et al 1992 60 17 18 Serousb Mucinous Endometrioid 1.4 0.9-2.2 1.2 0.6-2.5 2.8 1.2-6.4 Chang & Risch 1997 254 80 74 Serousb Mucinous Endometrioid 1.3 1.0-1.9 1.6 1.0-2.6 1.7 1.0-2.8 Cook et al 1997 131 Serous 43 Mucinous 36 Endometrioid 1.7 1.1-2.5 0.7 0.4-1.4 1.2 0.6-2.3 TALC Cramer et al 1999 229 83 Serous invasive Mucinous 1.7 1.2 2.4 0.8 0.4-1.4 130 Endometrioid cell 1.0 0.7 1.6 Wong et al 1999 136 11 21 Serous Mucinous Endometrioid 1.2 0.7-2.1 1.5 0.6-4.0 1.4 0.7-2.7 Gertig et al 2000 76 Serous invasive 1.4 1.0-1.9 Mills et al 2004 42 Serous invasive 10 Mucinous invasive 14 Endometrioid 1.8 1.1-2.8 1.1-2.8 2.6 0.9-7.4 1.3 0.6-2.6 CI confidence interval a Any or ever use of talc b Includes borderline and invasive serous tumours 367 368 IARC MONOGRAPHS VOLUME 93 under 75 years of age who underwent surgery for ovarian cancer at one of two cancer hospitals in Athens between June 1989 and March 1991. The controls were 200 women under 75 years of age who were residents of Greater Athens and who visited patients hospitalized in the same wards as the cases during the study period Ninety per cent of the eligible cases and 94 of the eligible controls agreed to participate hospital interviews were conducted to collect information on a range of demographic socioeconomic and reproductive factors as well as information on exposure to hair dyes analgesics tranquilizers and talc Exposure to talc was assessed qualitatively as yes application of talc in the perineal region In multivariable analyses models were adjusted for age in year groups education weight age at menarche menopausal status age at menopause parity age at first birth tobacco smoking status alcohol use coffee consumption and the other exposures of interest use of analgesics tranquilizers and hair dyes Application of talc to the perineal region was reported by six cases 3.2 and seven controls 3.5 to yield an odds ratio of 1.1 95 CI 0.3-4.0 after adjustment for the potential confounders Limitations of this hospital control study included the very low prevalence of perineal use of talc Purdie et al 1995 conducted a control study among women in the three most populous Australian Queensland New South Wales and Victoria Cases were women aged 18-79 years who had been diagnosed with epithelial ovarian cancer between August 1990 and December 1993 at gynaecological oncology treatment centres in one of these three regions Women were excluded if they had a metastatic tumour were outside the eligible age range could not be contacted were too ill or were incapable of completing the questionnaire in conjunction with a trained interviewer because of language difficulties or psychiatric conditions Each case was confirmed by an independent pathological review of tissue specimens Of 1116 cases identified during the study period 201 18 were ineligible e.g. due to a ovarian primary cancer or age at diagnosis Among the 915 eligible cases 824 90 agreed to participate and were interviewed Reasons for participation included death before interview 50 cases patient refusal 34 cases and physician refusal seven cases Controls were identified from the electoral roll and were similar to the cases in age distribution and area of residence Women were excluded as a control if they had a history of ovarian cancer or bilateral oophorectomy could not be reached or could not complete the questionnaire Among 1527 potential controls identified from the electoral roll 1178 were located and found to be eligible 77 Of these 860 agreed to participate in the study 73 of the eligible controls Reasons for ineligibility among the controls included failure to locate the individual 192 inability to complete the questionnaire due to language difficulties a psychiatric condition illness or death 105 previous bilateral oophorectomy 48 and age four Trained interviewers used a standardized questionnaire to collect information on medical reproductive family and occupational histories as well as data on dietary factors and history of talc use Questionnaires were administered face either in the clinic for cases or in the home of participant for some cases and all controls Covariates evaluated as potential confounders included parity hysterectomy tubal ligation duration TALC 369 of oral contraceptive use age education body mass index tobacco smoking status family history of cancer and multiple menstrual and reproductive factors Talc use around the abdomen or perineum was reported by 56.7 of cases and 52 of controls to yield an odds ratio of 1.3 95 CI 1.0 1.a5fter adjustment for parity Although enrolment in the electoral roll is mandatory in Australia the authors determined that 28 cases 3.4 had never enrolled and the enrolment status could not be confirmed for 46 cases 5.6 The results did not change when the analyses were limited to cases with confirmed enrolment in the electoral role Green et al 1997 evaluated the association between tubal ligation or hysterectomy and the risk for ovarian cancer using the Australian study population described by Purdie et al 1995 The analysis by Green et al 1997 used the same number of cases but five fewer controls than Purdie et al 1995 Duration of talc use was calculated as age at first reported use until age at occurrence of the earliest of any of the following events surgical sterilization reported last use of talc diagnosis or interview A modest increase in risk for ovarian cancer was observed with peritoneal use of talc odds ratio 1.3 95 CI 1.1-1.6 Neither duration of talc use nor age at first use were associated with risk for ovarian cancer although the relative risks 95 CI were not provided and the duration categories evaluated were not specified When compared with women with no history of genital exposure to talc and patent fallopian tubes women with a history of talc use and no history of surgical sterilization had the highest risk for ovarian cancer odds ratio 1.3 95 CI 1.0 1.w7hile women with a history of tubal ligation or hysterectomy and no talc use had the lowest risk odds ratio 0.6 95 CI 0.5-0.8 The primary limitation of this study was the restricted information on perineal use of talc] Shushan et al 1996 examined the association between exposure to fertility drugs and the risk for ovarian cancer among 200 cases of epithelial ovarian cancer 164 invasive and 36 borderline and 408 controls All participants were living in Israel and were 3664 years of age at enrolment into the study Cases were identified through the Israel Cancer Registry from January 1990 to September 1993. Among 287 women who met the eligibility criteria histologically confirmed diagnosis cancer diagnosed and reported during study period born between 1929 and 1957 and alive at time of interview 87 30.3 were excluded because of inability to locate the patient or physician 25 illness % refusal by the physician % or refusal by the patient % Controls were identified by random dialling and were matched to the cases by geographical area Women were eligible to be included as a control if they were born in the same period as the cases Potential controls were excluded if they had a history of bilateral oophorectomy % Of 2072 telephone calls that successfully reached a household member approximately half of the households 47.8 contacted had a potentially eligible woman who was at home Of these 16.2 refused to participate and 10.7 were excluded because the woman did not speak Hebrew Trained interviewers administered a standard questionnaire to all cases and controls The questionnaire collected detailed information on reproductive history use of oral contraceptives and fertility drugs as well as exposure to talc seldom moderate lot Although the main association of interest was use 370 IARC MONOGRAPHS VOLUME 93 of fertility drugs and the risk for ovarian cancer the authors reported that 21 cases 10.5 and 23 controls 5.6 had a history of moderate or frequent use of talc which yielded an unadjusted odds ratio of 1.97 P = 0.04 Limitations of this study included the very sparse information on talc use and the unavailability of adjusted results for the association between use of talc and the risk for ovarian cancer] Chang and Risch 1997 analysed the association between perineal use of powder and the risk for ovarian cancer among 450 cases and 564 population controls from metropolitan Toronto and southern Ontario Canada Cases were diagnosed between November 1989 and October 1992 and were between the ages of 35 and 79 years at entry into the study Of 631 cases identified during the study period 71.3 450 were interviewed and included in the analysis Reasons for participation included death 8.7 physician refusal 4.6 severe illness 4.8 loss to follow 2.7 and patient refusal 7.9 Potential controls were identified through records of the Ontario Ministry of Finance based on their residence and age were matched to cases within year age groups and were excluded from the study if they had a history of bilateral oophorectomy more than 1 year before entry into the study Among 873 eligible controls identified 309 35.4 did not participate Reasons included participant refusal 30.2 illness 1.9 or loss to follow 3.2 Interviewers administered a standard questionnaire during an home interview to obtain information on the history frequency and duration of use of talcum and cornstarch powder as well as multiple medical and reproductive covariates of interest Talc exposure was categorized on the basis of any exposure in the perineal area on the method of application directly to the perineum after bathing or showering dusting on sanitary napkins on the frequency of application < 10 10-25 25 applications per month and on the duration of exposure < 30 30-40 > 40 years of use Multiple logistic regression was used in the analyses with adjustment for age duration of oral contraceptive use parity defined as the number of term pregnancies duration of lactation for each pregnancy history of tubal ligation or hysterectomy and family history of breast or ovarian cancer Forty per cent of cases and % of controls reported any talc use in the perineal area to yield an odds ratio of 1.4 95 CI 1.1-1.9 Among the specific types of talc exposure application to the perineum after bathing was associated with a borderline significant increase in risk odds ratio 1.3 95 CI 1.0-1.7 while application on sanitary napkins a less common use in this study population was associated with an elevated but significant increase in risk odds ratio 1.3 95 CI 0.9 2.A0 borderline significant trend was seen with increasing duration of exposure to talc odds ratio per 10 years of exposure 1.1 95 CI 1.0 1.2 but not with increasing frequency of exposure An analysis of duration by category < 30 30 4>0 40 years did not suggest a response relationship odds ratios of 1.0 1.7 95 CI 1.1-2.6 1.4 95 CI 1.0-2.2 and 0.9 95 CI 0.5-1.4 respectively Use of cornstarch in the perineal area either alone or in conjunction with occasional talc was not associated with the risk for ovarian cancer although prevalence of use was low less than % of subjects To evaluate exposure pre- and 1970 as well as exposure pre- and tubal ligation or hysterectomy the authors assumed that participants initiated TALC 371 perineal use of after talc at the age of 20 years A similar significantly elevated risk for ovarian cancer was seen for use pre- and 1970 A higher odds ratio was seen for use of after talc before tubal ligation or hysterectomy odds ratio 1.1 95 CI 1.0-1.2 than for use after these surgical procedures odds ratio 1.0 95 CI 0.8-1.3 These estimates did not change when different starting ages between 15 and 24 years were used in the analysis The authors also evaluated the association between perineal use of talc and invasive and borderline cancers separately and found that the risk was elevated for both tumour types but was significant only for invasive tumours In addition risk was similar across the major histological subtypes of ovarian cancer serous mucinous endometrioid see Table 2.4 Limitations of this study included the lack of information on use of talc] Cook et al 1997 evaluated the association between use of genital powders or deodorants and the risk for ovarian cancer in a control study conducted in three counties of western Washington State USA Cases were aged 20-79 years at diagnosis were diagnosed with borderline or invasive epithelial ovarian cancer between 1986 and 1988 and were identified using the population Cancer Surveillance System of western Washington Controls were identified using random dialling were residents of the three counties of interest and were similar in age to the cases Among 512 eligible cases identified 329 were interviewed 64.3 and 313 were included in the analysis 61.1 A total of 183 eligible cases were not interviewed due to death 104 physician or patient refusal 73 or loss to follow six An additional 16 cases who were interviewed were excluded from the analysis because of white race seven and unknown genital use of powder nine Among 721 women identified as potential controls 521 were interviewed 72.3 and 422 were included in the analysis 58.5 Reasons for excluding interviewed controls from the analysis included white race 28 age greater than 79 years five history of bilateral oophorectomy 58 unknown oophorectomy status four and unknown genital use of powder four Information on powder use including the type method frequency and duration of use and the covariates of interest was collected during person interviews Covariates considered to be potential confounders in multivariable analyses included age education income marital status body mass index oral contraceptive use and parity A history of any lifetime genital powder use perineal dusting diaphragm storage use on sanitary napkins or use of deodorant spray was reported by 50.8 of cases and 39.3 of controls to yield an odds ratio of 1.5 95 CI 1.1-2.0 after adjustment for age Among the individual methods of genital use of powder risk was significantly elevated only for exclusive perineal dusting odds ratio 1.8 95 CI 1.2-2.9 after adjustment for age In analyses adjusted for age and other types of genital use of powder both perineal dusting odds ratio 1.6 95 CI 1.1-2.3 and genital deodorant spray odds ratio 1.9 95 CI 1.1-3.1 were associated with risk for ovarian cancer while use of powder on a diaphragm or on sanitary napkins was not associated with an increased risk There was no evidence of an increasing trend in risk with greater duration of perineal dusting but a significant positive trend was noted for both duration odds ratio 2.7 95 CI 1.1-6.6 for > 12 cumulative lifetime monthsp for 372 IARC MONOGRAPHS VOLUME 93 trend 0.05 and number of lifetime applications odds ratio 2.6 95 CI 0.9-7.6 for > 500 lifetime applications p for trend < 0.05 of genital deodorant spray The effect estimates did not change materially when perineal use of dusting powder after the date of tubal ligation or hysterectomy was excluded Risk was significantly elevated among women with any history of perineal dusting before 1976 odds ratio 1.8 95 CI 1.1 2.9 but the authors were unable to evaluate risk for use exclusively after 1976 due to the small number of women four cases and 10 controls who had had this exposure Among the individual types of powder evaluated cornstarch talcum powder baby powder deodorant powder scented body powder risk for ovarian cancer was non- significantly elevated for any use of talcum powder odds ratio 1.6 95 CI 0.9 2.8 and body powder use odds ratio 1.5 95 CI 0.9-2.4 after adjustment for age and other types of powder use yes The authors also evaluated the association between any genital use of powder and the risk for the major histological subtypes of ovarian cancer see Table 2.4 Risk was significantly elevated for serous tumours odds ratio 1.7 95 CI 1.1-2.5 and all other tumour types odds ratio 1.8 95 CI 1.1-2.8 but not for mucinous or endometrioid tumours Limitations of this study included the relatively low participation rates among the cases and controls Eltabbakh et al 1998 compared risk factors among 50 cases of primary extraovarian peritoneal carcinoma the study group and 503 cases of primary epithelial ovarian cancer the control group treated at Roswell Park Cancer Institute in Buffalo NY USA between October 1982 and October 1996. No healthy controls were enrolled in this study Diagnoses were reviewed by staff in the Division of Pathology study and control groups and were confirmed by a single pathologist as part of another study study group only Information on reproductive history menstrual history use of hormones and contraceptives and personal hygiene was collected through a administered item questionnaire which all patients were asked to complete during the hospital admission process All women who returned a questionnaire were eligible to be included in the study Among these patients the overall questionnaire response rate was % Response was inversely correlated with severity of disease and response rates were similar for the two diagnoses included in this study Because data on perineal talc use was missing for 37 patients in the control group only 466 ovarian cancer patients were included in the analysis Women who had primary ovarian cancer were significantly more likely to report a history of perineal use of talc compared with women who had primary peritoneal cancer 48.1 versus 26.0 crude odds ratio = 2.6 P 0.003 Among the other characteristics examined only age and age at menarche differed significantly in the two groups Limitations of this study included the minimal information on talc use the low questionnaire response rate among study participants particularly among the patients with more advanced disease the use of a administered questionnaire completed during the admissions process which may have limited the quality of the responses and the lack of a healthy comparison group Godard et al 1998 evaluated risk factors for familial and sporadic ovarian cancer in a population of French Canadian women in Montr^'alQuebec Canada Of 231 cases TALC 373 who were identified between 1995 and 1996 at two gynaecological oncology clinics in Montr^'al183 79.2 were interviewed and 170 73.6 were included in the analysis Reasons for inclusion were death 21 unavailability to participate n 12 loss to follow n = 15 and tumours were epithelial in origin n = 13 All cases were between the ages of 20 and 84 years at diagnosis with a mean age at diagnosis of 53.7 years and a mean age at interview of 55.9 years Controls were identified using a modified random dialling method and were frequency to cases by age within 1 year and French Canadian ethnicity The mean age at interview for the controls was 56.7 years Among 750 households contacted regarding participation in the study 66.7 n 500 either did not have an eligible female resident or did not reply to the researchers inquiries and 10.7 refused to participate A total of 170 women were interviewed and included in the analysis as controls A standardized item questionnaire was used to obtain information on the family medical and reproductive history of each participant Cases were interviewed either by telephone 30 or in the study clinics 70 No information was given on the methods of interview for control subjects Information on family history of cancer was collected to determine whether risk factors differed for the sporadic and familial cases of ovarian cancer Familial cases were those patients who had one or more family members first second or third degree relatives with breast cancer diagnosed before 55 years of age or ovarian cancer diagnosed at any age Sporadic cases were those patients who had no family members with breast cancer diagnosed before 55 years of age or with ovarian cancer diagnosed at any age Perineal exposure to talc was assessed qualitatively never with never as the baseline Covariates that were considered to be potential confounding variables were age at menarche age at menopause parity age at first and last childbirth duration of oral contraceptive use age at last oral contraceptive use tubal ligation alcohol use and previous breast or abdominal surgery Talc exposure was more common in cases than controls with 10.6 of the cases and 4.7 of the controls reported perineal use of talc P = 0.06 No difference between perineal use of talc was reported in the familial and sporadic cases P = 0.79 Multivariate analyses were performed comparing all cases all sporadic familial with controls In these analyses perineal use of talc was associated with a significant increase in the total risk for ovarian cancer odds ratio 2.5 95 CI 0.9 6.6 = 0.07 Risk was similarly significantly elevated for sporadic odds ratio 2.5 95 CI 0.9-7.1 and familial cases odds ratio 3.3 95 CI 0.9--12.4 compared with the controls Limitations of this study included its small size and the lack of any detailed information on perineal use of talc The control participation rates may have been low although this is not clear and it is not certain how representative the controls were] Cramer et al 1999 analysed the association between genital exposure to talc and the risk for primary epithelial ovarian cancer among 563 cases and 523 controls residing in eastern Massachusetts and New Hampshire USA Cases were identified between May 1992 and March 1997 through hospital tumour boards or statewide cancer registries Among 1080 cases diagnosed in this period including borderline tumours 203 18.8 374 IARC MONOGRAPHS VOLUME 93 were excluded due to death change of address inability to speak English no telephone in residence or a ovarian primary cancer Of the 877 eligible cases remaining after these exclusions 563 64 were included in the analysis The remaining 314 cases were excluded because of physician refusal n = 126 and patient refusal n = 136 Pathology reports were reviewed to confirm the diagnoses for all cases and slides were requested and reviewed in the case of discrepancies between the reported histology and the histology assigned based on the pathology report review Controls were identified by random dialling and town resident books to identify additional women over the age of 60 years who lived in Massachusetts and were frequency to cases by age within 4 years and location of residence Of the potentially eligible controls 72 of those identified by random dialling and 49 of those identified through town books agreed to participate All study participants were interviewed person using a standardized questionnaire to obtain information on their medical and reproductive histories family history and personal habits The questionnaire also asked multiple questions on powder use including route of exposure application to genital areas application to perineum sanitary napkins or underwear husband's use of powders in his genital area brand of powder used talc cornstarch age at first use duration and frequency of use 30 30-39 40 uses per month Participants were asked about exposures that occurred at least 1 year before the date of diagnosis cases or the date of interview controls The results were adjusted for the following potential confounding variables age state of residence body mass index parity oral contraceptive use family history of breast or ovarian cancer and history of tubal ligation The prevalence of talc use was higher among cases than controls 44.6 of cases and 36.1 of controls reported any use of talc included use in both genital and genital areas and 27.0 of cases and 18.2 of controls reported genital use of talc included dusting of perineum underwear either exclusively or in combination Talc use in genital areas was not associated with risk when compared with women who did not use personal powder odds ratio 1.1 95 CI 0.8-1.5 However genital use of talc was associated with a significant 60 increase in risk odds ratio 1.6 95 CI 1.2 2.W2 omen who reported more than one method of talc use in the genital area had an even greater risk for ovarian cancer odds ratio 2.2 95 CI 1.3 3.N6o association was observed between genital use of talc and risk for ovarian cancer among women who had undergone tubal ligation after adjustment for age odds ratio 1.0 95 CI 0.5-2.1 Because of the low prevalence of use < % of the study population of cornstarch evaluation of this product was uninformative When women who had been exposed to powder only in genital areas were excluded from the analysis no linear trend was observed between risk for ovarian cancer and age at first genital use of talc duration of use frequency of use or total number of lifetime applications However when genitally exposed women were included in the analysis a significant linear trend was observed with increasing number of lifetime applications after talc applications that occurred during ovulatory years or after tubal ligation or hysterectomy were excluded P = 0.02 Additional findings of interest included a significant increase in risk among married women with no TALC 375 personal talc use whose husbands had used talc for genital hygiene odds ratio 1.5 95 CI 0.9 2.a5nd a stronger association between genital use of talc and risk for ovarian cancer among women who had used talc before their first live birth odds ratio 1.6 95 CI 1.1-2.3 than for women who had used it exclusively after their first live birth odds ratio 1.0 95 CI 0.4-2.5 The association with genital use of talc was strongest for serous invasive tumours odds ratio 1.7 95 CI 1.2-2.4 No association was observed for endometrioid odds ratio 1.0 95 CI 0.7-1.6 or mucinous tumours odds ratio 0.79 95 CI 0.4-1.4 see Table 2.4 Wong et al 1999 reported the results of a control study conducted at Roswell Park Cancer Institute Buffalo NY USA of 499 cases treated between October 1982 and October 1992 largely those reported by Eltabbakh et al 1998 and 755 hospital controls The controls were randomly selected from a registry of patients who were being treated for gynaecological malignancies and were frequency to cases by age at diagnosis within 5 years The most common diagnoses among controls were colorectal 43.3 and skin cancers 34.5 and leukaemia 17.7 All participants completed the administered item questionnaire that all patients were asked to complete during the hospital admission process All analyses were adjusted for age at diagnosis parity oral contraceptive use tobacco smoking family history of ovarian cancer age at menarche menopausal status income education geographical location and history of tubal ligation or hysterectomy The analysis was restricted to 462 cases and 693 controls with information on perineal use of talc Ever use of talc genital or nongenital was reported by 47.8 of the cases and 44.9 of the controls while use of talc in the genital or thigh area was reported by 34.0 of the cases and 32.2 of the controls There was no association between any method of talc use and the risk for ovarian cancer after adjusting for several potentially confounding variables The adjusted odds ratio for talc use in the genital or thigh area was 1.0 95 CI 0.8 1.D3uration of talc use was similar in the cases and controls and no association between talc use and the risk for ovarian cancer was found for any duration category No significant association was observed between talc use and any of the major histological subtypes of ovarian cancer see Table 2.4 the odds ratio for serous cystadenocarcinoma was 1.2 95 CI 0.7 2.1 No evidence was found of effect modification by history of tubal ligation or hysterectomy Among women who had not undergone tubal ligation or hysterectomy the odds ratio for the association between talc use and risk for ovarian cancer was 1.2 95 CI 0.8 1.w6hile among women who had undergone tubal ligation or hysterectomy the odds ratio was 0.8 95 CI 0.5-1.2 Limitations of the study included the sparse information on talc use In addition the use of hospital controls with gynaecological malignancies may have caused selection bias As noted in the earlier report by Eltabbakh et al 1998 the response rate to the questionnaire was low in this study population particularly among the patients with more advanced disease] Ness et al 2000 examined whether factors related to an inflammatory response of the ovarian epithelium such as exposure to talc endometriosis cysts and hyperthyroidism played a role in the risk for ovarian cancer The study was conducted 376 IARC MONOGRAPHS VOLUME 93 among 767 recently diagnosed cases of epithelial ovarian cancer and 1367 based controls Cases were aged 20-69 years and were identified between 199p4opaunldat1i9o9n8- at 39 hospitals in the Delaware Valley region USA Of 1253 61.2 were interviewed and included in the potentially eligible cases the analysis Reasons for excluding women from study included diagnosis more than 6 months before the interview n 296 severe illness or death n = 69 unavailability of contact information = 15 physician refusal n 14 or patient refusal n = 92 Controls were identified through random dialling for controls /6y5ears of age and Health Care Financing Administration lists controls 65-69 years of age and were frequency to cases by age and locationfoorf residence Overall 72 of the eligible potential controls agreed to participate in the study A pathological review was conducted for a subset of the cases n = 120 When compared with the original diagnosis the central review was 95 concordant for invasiveness and 82 concordant for cell type The original pathological diagnosis was used in the for all cases A analysis standardized hour interview was conducted in the homes of the participants to collect information on menstrual and reproductive history sexual activity use of contraceptives history and duration of talc use genital and genital applications and exposure via male sexual partners Talc use was categorized according to the method of application never feet genital sanitary napkins underwear diaphragm or cervical cap or male partner and duration of exposure < 1 year 1-4 years 5-9 years > 10 years Unconditional logistic regression adjusted for age parity race family history of ovarian cancer oral contraceptive use tubal ligation hysterectomy and lactation was used in all analyses A history of talc use in the genital area was reported by 161 cases 21.0 and 219 controls 16.0 to yield an adjusted odds ratio of 1.5 95 CI 1.1-2.0 Significant associations were also observed for the use of talc on sanitary napkins odds ratio 1.6 95 CI 1.1-2.3 and on underwear odds ratio 1.7 95 CI 1.2-2.4 The use of talc on the feet arms or breasts was associated with a significant 40 increase in risk however women may also have used talc on more than one area of the body including the genital and rectal area Use of talc on diaphragms or cervical caps and use by a male sexual partner were not associated with the risk for CI ovarian cancer There was no clear trend between risk for ovarian cancer and increasing duration of use of talc on the genital and rectal area or feet Adjusted odds ratios of 2.0 95 CI 1.0-4.0 1.6 95 CI 1.1-2.3 1.2 95 CI 0.8-1.9 and 1.2 95 1.0-1.5 were observed for < 1 year 1-4 years 5-9 years and 10 10 years of use respectively Limitations of this analysis included the sparse information on talc use In ] analyses of duration the use of talc on the feet was also included as an exposure The relatively low participation rates among cases was also a limitation of the study Langseth and Kjaerheim 2004 described in detail in Section 2.1.2 evaluated the association between employment in the pulp and paper industry in Norway and the risk for ovarian cancer In addition to the assessment of occupational exposure information was collected on hygienic use of talc and potential confounders for a subset of the cases and controls during a personal interview conducted at the mills or by telephone Exposure to hygienic talc products was categorized as never for personal use on diapers TALC 377 sanitary napkins underwear or husband's use in the genital area Thirty cases and 102 of the eligible controls or their next of kin agreed to an interview and an additional 19 women who were not cases were interviewed and included in secondary analyses as supplementary controls A family member completed the interview due to the death of the case or control for 25 of the cases and 31 of the controls Use of talc on the genital area was reported by 12 cases and 53 controls to yield an odds ratio of 1.2 95 CI 0.43.2 The primary limitations of this analysis were the small number of cases the small percentage of cases and controls who were interviewed to obtain information on the covariates of interest and use of surrogate respondents to obtain information on covariates for the deceased cases and controls The Working Group noted that hygienic exposure to talc was assessed retrospectively in the nested control study] Mills et al 2004 evaluated the association between perineal exposure to talc and the risk for ovarian cancer in an ethnically diverse population from 22 counties of central California USA The study included 256 incident cases diagnosed between 1 January 2000 and 31 December 2001 and identified through two regional cancer registries using rapid case ascertainment procedures and 1122 controls identified by random dialling Controls were frequency to the cases by age and ethnicity Pathology reports were reviewed centrally for a subset of the cases to confirm the diagnosis subtype and invasiveness of each cancer Potential controls were ineligible for inclusion in the study if they were under 18 years of age were not a resident of the counties of interest or if they had a history of epithelial ovarian cancer or bilateral oophorectomy Among 652 cases identified during the study period 263 40.3 were excluded due to language or hearing difficulties n = 17 death n = 76 physician refusal n = 10 severe illness n 41 or unavailability of current contact information n = 119 Of the 389 eligible cases who were contacted regarding participation in the study 256 65.8 agreed to participate and were interviewed Of a total of 2327 potential controls 740 31.8 were excluded from the study due to age n = 80 location of residence n = 21 language difficulties n = 10 previous bilateral oophorectomy n = 252 severe illness n = 19 or change of address or telephone number or inability to contact the woman after repeated attempts n 358 Of the 1587 potential controls who were contacted and found to be eligible 1122 70.7 agreed to participate and were interviewed All cases and controls were interviewed by telephone to obtain information on their medical history covariates of interest and history of perineal exposure to talc including the frequency duration and calendar years of use Information on talc use was unavailable for seven cases and 17 controls thus the final study population for this analysis included 249 cases and 1105 controls For the final models unconditional logistic regression adjusted for age ethnicity duration of oral contraceptive use and breastfeeding was used Additional covariates considered to be potential confounders included family history of breast cancer or ovarian cancer parity history of pregnancy body mass index hysterectomy tubal ligation and duration of postmenopausal use of hormones A history of perineal talc use was reported by 42.6 of the cases and 37.1 of the controls to yield an adjusted odds ratio of 1.4 95 CI 1.0-1.9 A significant trend P = 0.015 with increasing frequency 378 IARC MONOGRAPHS VOLUME 93 of talc use was observed The greatest risk for ovarian cancer was observed among women with the highest frequency of use odds ratio 1.7 for use 4-7 times per week 95 CI 1.1 2.T6here was a borderline significant trend with increasing duration of use P = 0.045 The highest risk was observed among women with 4-12 years of use odds ratio 1.9 95 CI 1.2-3.0 and elevated but significant risks were seen among women with longer durations of use with odds ratios of 1.5 95 CI 0.9-2.3 and 1.2 95 CI 0.7 2.f1or 13-30 and > 30 years of use respectively A borderline significant trend was noted for cumulative talc use frequency times duration of use although this was also not clear P = 0.051 The highest risks were observed in the second and third quartiles of cumulative talc use When examined according to the time of use the risk was higher among women who had first used talc after 1975 odds ratio 1.9 95 CI 1.3-2.9 than among those who had first used talc before or during 1975 odds ratio 1.2 95 CI 0.8 1.R8isk was also higher among women who were aged 20 years or more at first talc use than among those who were under 20 years of age and among women who initiated talc use after their first birth than among those who had some use before their first birth When time since last use was examined women who had last used talc 1- 2 years previously had the highest risk odds ratio 2.4 95 CI 1.4-4.1 women who had last used it 3-20 years previously had an elevated but significant risk for ovarian cancer odds ratio 1.6 95 CI 0.9-2.7 Modification of the association between perineal use of talc and risk for ovarian cancer by tubal ligation hysterectomy parity oral contraceptive use postmenopausal use of hormones and body mass index was also evaluated Risk was higher among women who had not had tubal ligation odds ratio 1.5 95 CI 1.1 2.t2han among those who had odds ratio 0.9 95 CI 0.5-1.7 although the interaction was not statistically significant Risk was also higher among women who had ever been pregnant odds ratio 1.4 95 CI 1.1-2.0 than among those who had never been pregnant odds ratio 0.9 95 CI 0.4 2.a3nd among women who had no history of oral contraceptive use odds ratio 1.6 95 CI 1.0 2.t6han among those who had used oral contraceptives odds ratio 1.3 95 CI 0.9-1.8 No evidence was found of a modification of effect by hysterectomy status body mass index or postmenopausal use of hormones Limitations of this study included the low participation rate and relatively small number of cases In addition pathology was not confirmed for all cases which may have resulted in some misclassification of histological subtype] 2.3 Use of talc in pleurodesis The use of talc or iodized talc to produce pleurodesis began in the 1930s as a treatment for recurrent spontaneous pneumothorax or pleural effusions The therapy involves the introduction of 0.5-10 g talc directly into the pleura using intrapleural injection In recent decades the therapy has most commonly been restricted to use for the treatment of malignant pleural effusions An individual case report described a lung adenocarcinoma that was diagnosed 2 years after pleurodesis with iodized talc Jackson & Bennett 1973 TALC 379 a A survey was reported Research Committee of the British Thoracic Association and the Medical Research Council Pneumoconiosis Unit 1979 of the term effects of pleurodesis with talc and kaolin among series of British patients who were followed for 14-40 years The one talc mentioned BP Indian Finex was reported not to contain fibrous amphiboles but it was unclear if that was true of all the talcs used Three lung cancers were observed 2.14 expected P 0.3 among 210 talc pleurodesis patients Two of the lung cancer patients developed tumours on the opposite side from where treatment had occurred month and year intervals between treatment and death The third patient had an oat cell carcinoma site unknown and died 32 years after treatment No cases of mesothelioma were reported Viskum et al 1989 reported on 99 Danish patients who had been treated in 1954-64 by pleurodesis with talc at doses that ranged from 0.5 to 4.9 g and who were followed for at least 20 years Three deaths from lung cancer occurred expected number of cases not provided one on the side opposite from where treatment had occurred and two with no origin reported No cases of mesothelioma were reported The Working Group noted that these reports are difficult to interpret because of the high prevalence of lung disease in the patient groups which could be related to risk factors such as tobacco smoking The type or source of talc used was not clear although it was assumed to be pharmaceutical grade No case of mesothelioma was observed but the number of expected cases would probably be very low 2.4 References Blum S Arp EW Jr Smith AH Tyroler HA 1979 Stomach cancer among rubber workers an epidemiologic investigation In Lemen R. Dement JM eds Dusts and Disease Proceedings of the Conference on Occupational Exposures to Fibrous and Particulate Dust and Their Extension into the Environment Park Forest South IL Pathotox Publisher Inc. pp 325 Booth M Beral V Smith P 1989 Risk factors for ovarian cancer a control study Cancer 592 5928679848 334 Br J Chang S Risch HA 1997 Perineal talc exposure and risk of ovarian carcinoma Cancer 2396-2401 10.1002 19970615 3.0.CO M. 9191529 Chen Y Wu C Lang H et al 1992 Risk factors for epithelial ovarian cancer in Beijing China Int J Epidemiol 23-29 10.1093 21.1.23 PMID 1544753 Coggiola M Bosio D Pira E et al 2003 An update of a mortality study of talc miners and millers in Italy Am J Ind Med 63-69 10.1002 ajim 10240. PMID 12822137 Cook LS Kamb ML Weiss NS 1997 Perineal powder exposure and the risk of ovarian cancer Am J Epidemiol 459 4695048520 Cramer DW Liberman RF Ernstoff L et al 1999 Genital talc exposure and risk of ovarian cancer Int J Cancer 351 351 6 097-0215 81 AID- 3.0.CO 10209948 380 IARC MONOGRAPHS VOLUME 93 Cramer DW Welch WR Scully RE Wojciechowski CA 1982 Ovarian cancer and tale a casecontrol study Cancer 372-376 10.1002 19820715 CNCR2820500235 7083145 Eltabbakh GH Piver MS Natarajan N Mettlin CJ 1998 Epidemiologic differences between women with extraovarian primary peritoneal carcinoma and women with epithelial ovarian cancer Obstet Gynecol 254-259 10.1016 S0029-7844 9469285 Gertig DM Hunter DJ Cramer DW et al 2000 Prospective study of talc use and ovarian cancer J Natl Cancer Inst 249 2592 2.3.249 10655442 Godard B Foulkes WD Provencher D et al 1998 Risk factors for familial and sporadic ovarian cancer among French Canadians a control study Am J Obstet Gynecol 403-410 S0002-9378 9731846 Green A Purdie D Bain C et al Survey of Women's Health Study Group 1997 Tubal sterilisation hysterectomy and decreased risk of ovarian cancer Int J Cancer 948-951 1097-0215 3.0.CO 9185694 Harlow BL Cramer DW Bell DA Welch WR 1992 Perineal exposure to talc and ovarian cancer risk Obstet Gynecol 19-26 PMID 1603491 Harlow BL Weiss NS 1989 A control study of borderline ovarian tumors the influence of perineal exposure to talc Am J Epidemiol 390 3924750733 Hartge P Hoover R Lesher LP McGowan L 1983 Talc and ovarian cancer JAMA 1844 jama.250.14.1844 6620481 Hartge P Stewart P 1994 Occupation and ovarian cancer a control study in the Washington DC metropolitan area 1978-1981 J Occup Med 924-927 7807277 Jackson JW Bennett MH 1973 Chest wall tumour following iodized talc pleurodesis Thorax 788-793 thx.28.6.788 4787992 Katsnelson BA Mokronosova KA 1979 fibrous mineral dusts and malignant tumors an epidemiological study of mortality J Occup Med 15-20 215733 Langseth H Andersen A 1999 Cancer incidence among women in the Norwegian pulp and paper industry Am J Ind Med 108-113 10.1002 AJIM15 10361594 Langseth H Kjaerheim K 2004 Ovarian cancer and occupational exposure among pulp and paper employees in Norway Scand J Work Environ Health 356 36115529799 Leophonte P Basset MF Pincemin J et al 1983 Mortality of talc workers in France a retrospective epidemiological study Rev Fr Mal Respir 489-490 Leophonte P Didier A 1990 French talc pneumoconiosis In Bignon J. ed Health Effects of Phyllosilicates Berlin Heidelberg Springer pp 203--209 Mills PK Riordan DG Cress RD Young HA 2004 Perineal talc exposure and epithelial ovarian cancer risk in the Central Valley of California Int J Cancer 458 464 ijc.20434 15382072 Ness RB Grisso JA Cottreau C et al 2000 Factors related to inflammation of the ovarian epithelium and risk of ovarian cancer Epidemiology 111-117 00001648- 200003000-00006 PMID 11021606 C Purdie D Green A Bain et al Survey of Women's Health Study Group 1995 Reproductive and other factors and risk of epithelial ovarian cancer an Australian control study Int J Cancer 678-684 10.1002 ijc.2910620606 7558414 TALC 381 Research Committee of the British Thoracic Association and the Medical Research Council Pneumoconiosis Unit Research Council Pneumoconiosis U 1979 A survey of the term effects of talc and kaolin pleurodesis Br J Dis Chest 285-288 10.1016 90054-8 553661 Rosenblatt KA Szklo M Rosenshein NB 1992 Mineral fiber exposure and the development of ovarian cancer PMID 1601331 Gynecol Oncol 20-25 0090-8258 Rubino GF Scansetti G Piolatto G 1979 Mortality and morbidity among talc miners and millers in Italy In Lemen R. Dement J.M. eds Dusts and Disease Proceedings of the Conference on Occupational Exposures to Fibrous and Particulate Dust and Their Extension into the Environment Park Forest South IL Pathotox Publisher Inc. 357-363 Rubino GF Scansetti G Piolatto G Romano CA 1976 Mortality study of talc miners and millers J Occup Med 187 19030043764-197603000-00013 1255280 Selevan SG Dement JM Wagoner JK Froines JR 1979 Mortality patterns among miners and millers of asbestiform tale preliminary report J Environ Pathol Toxicol 273-284 512559 Shushan A Paltiel O Iscovich J et al ( 1996 Human menopausal gonadotropin and the risk of epithelial ovarian cancer Fertil Steril 13-18 8557128 Siemiatycki J editor 1991 Risk Factors for Cancer in the Workplace Boca Raton FL CRC Press Straif K Chambless L Weiland SK et al 1999 Occupational risk factors for mortality from stomach and lung cancer among rubber workers an analysis using internal controls and refined exposure assessment 10661645 Int J Epidemiol 1037-1043 28.6.1037 Straif Keil U Taeger D et al 2000 Exposure to nitrosamines carbon black asbestos and tale and mortality from stomach lung and laryngeal cancer in a cohort of rubber workers Am Epidemiol 297-306 152.4.297 10968374 Thomas TL Stewart PA 1987 Mortality from lung cancer and respiratory disease among pottery workers exposed to silica and talc Am J Epidemiol 35-43 3024482 Tzonou A Polychronopoulou A Hsieh C et al 1993 Hair dyes analgesics tranquilizers and perineal talc application as risk factors for ovarian cancer Int J Cancer 408 414008 410 ijc.291055031ijc3.29105 03138375924 Viskum K Lange P Mortensen J 1989 Long term sequelae after talc pleurodesis for spontaneous pneumothorax Pneumologie 105-106 2717548 Wergeland E Andersen A Baerheim A 1990 Morbidity and mortality in exposed workers Am J Ind Med 505 51a3jim.4700170408 2327417 Whittemore AS Wu ML Paffenbarger RS Jr et al 1988 Personal and environmental characteristics related to epithelial ovarian cancer II Exposures to talcum powder tobacco alcohol and coffee Am J Epidemiol 1228-1240 3195564 Wild P. 2000 An epidemiolgical mortality study in the producing industry Study Report INRS Report TMT Paris Institut National de la Recherche Scientifique in French Wild P 2006 Lung cancer risk and talc not containing asbestiform fibres a review of the epidemiological evidence Occup Environ Med 4-9 oem.2005.020750 16361399 382 IARC MONOGRAPHS VOLUME 93 Wild P Leodolter K R^'fr^'gierM et al 2002 A cohort mortality and nested control study of French and Austrian talc workers Occup Environ Med 98-105 oem.59.2.98 PMID 11850552 Wong C Hempling RE Piver MS et al 1999 Perineal talc exposure and subsequent epithelial ovarian cancer a control study Obstet Gynecol 372-376 10.1016 00439-6 PMID 10074982 Wu ML Whittemore AS Paffenbarger RS Jr et al 1988 Personal and environmental characteristics related to epithelial ovarian cancer I. Reproductive and menstrual events and oral contraceptive use Am J Epidemiol 1216-1227 3195563 TALC 383 3. Studies of Cancer in Experimental Animals The Working Group identified an issue that relates to the interpretation of several of the inhalation and intratracheal instillation studies of talc A lesion that is frequently seen in rats that have been exposed by inhalation to a range of poorly soluble particles such as talc has been described variously as proliferating squamous cyst proliferative keratinizing cyst proliferating squamous epithelioma benign cystic keratinizing squamous tumour or cystic keratinizing squamous tumour Various authors have included this lesion in tumour counts but the neoplastic nature of this lesion has been debated Kittel et al 1993 Carlton 1994 Mauderly et al 1994 Boorman & Seely 1995 Rittinghausen et al 1997 Rittinghausen & Kaspareit 1998 its relationship to pulmonary neoplasia is uncertain The Working Group noted that in many of the studies of tale described below no or limited characterization of the mineralogy of the sample employed was given and in particular that there was a lack of information on fibre content or particle size 3.1 Oral administration Rat Groups of 25 male and 25 female Wistar rats 10 weeks of age received about 50 mg body weight bw per day of commercial talc characteristics unspecified in the diet average survival 649 days or standard diet alone for life average survival 702 days No significant difference in tumour incidence was found in the treated animals compared with control animals Gibel et al 1976 Groups of 16 male and 16 female derived rats 21-26 weeks of age were fed 100 mg Italian talc grade 00000 ready milled mean particle size 25 mcontaining 92 talc % chlorite % carbonate minerals and 0.5-1 quartz per day per rat in the diet for 5 months containing diet was actually given for 101 days and were then maintained on basal diet for life average survival 614 days No differences in tumour incidence were noted between treated animals and eight male and eight female control animals fed basal diet throughout average survival 641 days Wagner et al 1977 The Working Group noted the limited exposure period and the advanced age of the animals at the start of the study 384 IARC MONOGRAPHS VOLUME 93 3.2 Inhalation exposure 3.2.1 Mouse Groups of 47-49 male and 48-50 female B6C3F mice 7 weeks of age that were fed an NIH diet were exposed by inhalation to aerosols containing 0 6 or 18 mg MP 10-52 grade talc for 6 hours per day on 5 days per week for up to 104 weeks dose equivalent 0 2 or 6 mg bw per day for male mice and 0 1.3 or 3.9 mg bw per day for female mice MP 10-52 grade is a purity microtalc from a strip mine located in Missouri State USA that has a maximal particle size of 10 ...mand is reported to contain no tremolite or any asbestiform minerals After analysis the talc was found to be free of asbestos and almost free of silica The average mass mean aerodynamic diameter MMAD and the geometric standard deviation GSD of the talc aerosols were calculated to be 3.3 -1.9 ...mand 3.6 -2.0 ...mfor the 6- and mg chambers respectively At approximately week 70 difficulties were experienced in generating the talc aerosol and the chamber concentrations were substantially lower than the target concentrations over a period of 12 weeks Survival and final mean body weights of male and female mice exposed to talc were similar to those of the controls and no clinical findings were attributed to exposure to talc No significant increases in the incidence of neoplasms were observed The incidence of pulmonary neoplasms males 27 % and % females % % and % was similar between exposed and control groups of mice The Working Group noted that the incidence of bronchiolar adenoma or carcinoma combined in historical control B6C3F mice fed an NIH diet in National Toxicology Program inhalation studies was 26.8 for males and 10.1 for females National Toxicology Program 1993 3.2.2 Rat Two groups of 12 male and 12 female derived rats 6-8 weeks of age were exposed by inhalation to a mean respirable dust concentration of 10.8 mg Italian talc grade 0000 ready milled mean particle size 25 ...min diameter containing 92 talc % chlorite % carbonate minerals and 0.5-1 quartz for 7.5 hours per day on 5 days a week for 6 or 12 months cumulative exposures 8200 and 16 400 mg h respectively Ten days after the end of each exposure period six rats per group were killed 12 rats per group died and two rats per group were unaccounted for the remaining four rats per group were killed 1 year after the end of the exposure period No differences were noted in the incidence of lung tumours compared with 24 male and 24 female untreated controls Wagner et al 1977 The Working Group noted the limited number of animals allowed to survive longer than 12 months after the end of each exposure period] Groups of 49 or 50 male and 50 female Fischer 344 rats 6-7 weeks of age were exposed by inhalation to aerosols of 0 6 or 18 mg MP 10-52 grade talc see Section 3.2.1 for 6 hours per day on 5 days per week until mortality in any exposure group TALC 385 reached 80 113 weeks for males and 122 weeks for 8.4 mg bw per day for males GSD females dose equivalent 0 2.8 or and 0 3.2 or 9.6 mg bw per day for females The average MMAD and the GSD of the talc aerosols were calculated to be 2.7 - and 3.2 ...mfor the 6- and 1.9 m mg chamber concentration for the chambers respectively At week 11 the mg 40 mg for a period of 7 weeks group varied from approximately 30 to aerosol because of difficulties with the systems used to monitor concentration In addition at approximately week 70 difficulties were significantly greater than those of controls at the 6- 11- and month interim and at the end of the lifetime study while those of female evaluations significantly greater at the 1- 11- 18- and rats exposed to 18 mg were lifetime month interim evaluations and at the end of the study Exposure to talc produced a spectrum of inflammatory reparative and proliferative processes in the lungs The principal toxic lesions observed granulomatous inflammation alveolar included chronic epithelial hyperplasia squamous metaplasia squamous cysts and interstitial fibrosis of the lung The authors considered that the carcinoma 0/50 dose 0/48 dose 13/50 carcinoma 5/50 and significantly greater P 0.001 in the dose than in was P 0.028 The incidence of group controls carcinoma that in pulmonary neoplasms in exposed male rats was similar to controls Adrenal medulla pheochromocytomas benign and malignant occurred with a significantly positive trend in males combined dose 37/47 0.007 and females control 26/49 dose 32/48 control 13/48 dose 14/47 dose ] malignant pheochromocytomas in females was 10/49 P = 0.001 Although adrenal medulla control 0/48 dose 1/47 dose among exposed and control hyperplasia occurred with similar frequency females the incidence of hyperplasia in exposed males was significantly lower than that in controls National Toxicology Program Working Group noted that some authors have indicated that stress and 1993 The to a proliferation of chromaffin cells and hypoxia may lead in the incidence of these eventually to pheochromocytomas An increase tumours was also observed in several other National Program studies that used particulates and the Toxicology incidence ofthis type of tumour same rat strain in which the background The Working Group also was quite high Ozaki et al 2002 Melnick et al 2003 noted inhalation studies that this type of tumour was not reported in particle other than those of the National Toxicology Program and hence felt that this increase may not be related to talc 386 3.2.3 Hamster IARC MONOGRAPHS VOLUME 93 In a lifetime experiment three groups of 50 male and hamsters 4 weeks of 50 female Syrian golden age were exposed by inhalation to an aerosol of talc that was prepared from Vermont talc by flotation baby powder quantities of magnesite dolomite chlorite and 95 w platy talc with trace rutile for 3 30 or 150 minute per day on and 25 females The survivors of the last two 20 months At that exposed groups were killed at the age of time 20 of the males were still alive and all females primary tumours were observed in the were dead No incidence of alveolar hyperplasia inlutnhges in any of the hamsters although the 150 minutes per day for 300 days was 25 groups given talc aerosol for 30 or Wehner et al 1977 1979 The compared with % in the control group the high mortality rate Working Group noted the short daily exposure time and 3.3 Intratracheal administration Hamster Four groups of 24 male and 24 female Syrian golden hamsters 9 weeks received 18 weekly intratracheal instillations of 3 of age % magnesium oxide 32-34 other mg talc USP grade silica oxide 61- dusts 0.85-1.06 0.85-1.06 93.3 25 min diameter in 0.2 mL saline with or without 3 mg pyrene or 0.2 mL saline alone untreated The animals were allowed to live out their or were 55 weeks No respiratory tract tumours lifespan average 50 survival 46 were observed in the treated treated or survival of the animals 3.4 Mouse Subcutaneous administration of Fifty female R3 mice 3-6 months of age were given single subcutaneous injections of 0.2 mL about 80 a mixture of 8 g tale type unspecified and 20 g peanut oil delivered dose mg and were observed for life average 50 survival 596 days No local tumour was observed Neukomm & de Trey 1961 3.5 Intraperitoneal administration 3.5.1 Mouse intraperitoneally In a study that investigatedinvestigated the to response intraperitoneally injected asbestos control groups of 12 four five six five and 12 white male mice with age unspecified were injected a mL suspension 50 of talc in saline and killed 147 170 and 343 days after injection respectively Talc 26 57 112 0000 Talc USP V no further was described as 6505-147- analysis was made Histopathological examination was treated controls Bischoff & Bryson 1976 Fourty Swiss albino mice sex unspecified 6 weeks of intraperitoneal injection of 20 age received a single saline Within 6 mg ground commercial talc type unspecified in 1 mL months 16 animals had died In the 24 survivors allowed to live normal lifespan three peritoneal mesotheliomas out their 3/46 treated controls ^ zesmi et al 1985 were observed compared with The Working Group noted the occurrence of mesotheliomas in treated animals ] 3.5.2 Rat A group of 40 female Wistar rats 8-12 weeks of injections of 25 age received four intraperitoneal mg granular talc characteristics unspecified in 2 mL saline intervals A group of 80 female rats at weekly was injected with 2 mL saline alone and served as controls The rats were observed until spontaneous death or when killed in moribund 388 IARC MONOGRAPHS VOLUME 93 3.6 Intrapleural and intrathoracic administration 3.6.1 Mouse In a study reported as an abstract male Marsh mice 3 months of age received a single intrathoracic injection of 10 mg USP talc After 18-21 months 5/47 treated mice had tumours two adenocarcinomas and three lymphoid tumours of the lung compared with none of 48 injected controls Bischoff & Bryson 1976 3.6.2 Rat In a study reported as an abstract female Evans rats 3 months of age received single intrathoracic injections of 50 mg USP talc After 18-21 months intrathoracic reticulumcell sarcomas or lymphomas were observed in 7/30 treated rats 8/32 treated rats and 7/28 untreated controls Bischoff & Bryson 1976 In a lifetime study a group of 24 male and 24 female derived rats 8-14 weeks of age received a single intrapleural injections of 20 mg Italian talc grade 00000 ready milled mean particle size 25 ...mcontaining 92 talc % chlorite % carbonate minerals and 0.5-1 quartz in 0.4 mL saline The mean survival time of the treated rats 655 days was similar to that of 24 male and 24 female controls 691 days that were injected with saline No mesothelioma was detected in either group one small pulmonary adenoma was found in one treated rat that died 25 months after injection Wagner et al 1977 Following thoracotomy groups of 30-50 female Osborne rats 12-20 weeks of age received intrapleural implantations of 40 mg of one of seven grades of refined commercial talc from separate sources in hardened gelatin The rats were followed for 2 years at which time survivors were killed The incidence of pleural sarcomas was talc 1 1/26 talc 2 1/30 talc 3 1/29 talc 4 1/29 talc 5 0/30 talc 6 0/30 talc 7 0/29 untreated controls 3/488 0.6 and controls that received implants of fibrous materials described by the authors as carcinogenic 17/598 % Stanton et al 1981 3.7 Ovary implantation Rat In a study that investigated the effect of implanted talc on the rat ovary a group of 10 female Sprague rats 10-15 weeks of age received implants of 100 Lof a tale suspension in saline 100 mL onto the surface of the ovary by intrabursal injection The talc was described as Italian 00000 particle size 0.3-14 ...mand contained no asbestos Three operated and three treated control animals were included Animals were killed after 12 months and histopathological examination of the ovaries was performed Small focal areas of papillary change that were considered to be TALC 389 preneoplastic changes were seen in the surface epithelium of 4/10 treated animals 0/6 controls No neoplasms were reported Hamilton et al 1984 The Working Group noted that groups of animals implanted for , 3 6 or 18 months were also included but no results were reported for any of these groups 3.8 References Bischoff F Bryson G 1976 Talc at the rodent intrathoracic intraperitoneal and subcutaneous sites Abstract No.1 Proc Am Assoc Cancer Res 17 Boorman GA Seely JC 1995 The lack of an ovarian effect of lifetime talc exposure in F344 rats and B6C3F1 mice Regul Toxicol Pharmacol 242-243 rtph.1995.1035 7644712 Carlton WW 1994 Proliferative keratin cyst a lesion in the lungs of rats following chronic exposure to aramid fibrils 'Fundam Appl Toxicol 304 307 10.1006 1994.1108 1994.1108 7526997 Gibel W Lohs K Horn KH et al 1976 Experimental study on cancerogenic activity of asbestos filters Arch Geschwulstforsch 437 44i2n German 999453 Hamilton TC Fox H Buckley CH et al 1984 Effects of talc on the rat ovary BrJ Exp Pathol 101 1066696826 Jagatic J Rubnitz ME Godwin MC Weiskopf RW 1967 Tissue response to intraperitoneal asbestos with preliminary report of acute toxicity of treated asbestos in mice Environ Res 217 230 0 013-9351 4303313 Kittel B Ernst H Dungworth DL et al 1993 Morphological comparison between benign keratinizing cystic squamous cell tumours of the lung and squamous lesions of the skin in rats Exp Toxicol Pathol 257-267 7508775 Mauderly JL Snipes MB Barr EB et al 1994 Pulmonary toxicity of inhaled diesel exhaust and carbon black in chronically exposed rats Part I Neoplastic and nonneoplastic lung lesions Res Rep Health Eff Inst 1-75 discussion 77 97 7 530965 Melnick RL Bucher JR Roycroft JH et al 2003 Carcinogenic and toxic effects of inhaled non- fibrous poorly soluble particulates in rats and mice contradict threshold lung cancer hypotheses that are dependent on chronic pulmonary inflammation .. EurJ Oncol 177 186 National Toxicology Program 1993 Toxicology and Carcinogenesis Studies of Talc CAS No. 14807-96-6 in F344 Rats and B6C3F Mice Inhalation Studies Tech Rep Ser 421 Research Triangle Park NC Available at http://ntp.niehs.nih.gov/ntp/htdocs/LT_rpts/tr421.pdf htp:/ntp.niehs.nih.gov/ntp/htdocs/LT_rpts/tr421.pdf Neukomm S de Trey M 1961 Study of possible carcinogenic and carcinogenic brightening agents Med Exp 298 30i6n French Ozaki K Haseman JK Hailey JR et al 2002 Association of adrenal pheochromocytoma and lung pathology in inhalation studies with particulate compounds in the male F344 rat- the National Toxicology Program experience Toxicol Pathol 263 270 doi 019262302753559605 11950170 ^ zesmiM Patiroglu TE Hillerdal G ^ zesmiC 1985 Peritoneal mesothelioma and malignant lymphoma in mice caused by fibrous zeolite Br J Ind Med 746 7429998433 390 IARC MONOGRAPHS VOLUME 93 Pott F Dolgner R Friedrichs H Huth F 1976b The oncogenic effect of fibrous dust Animal experiments and their relationship with human carcinogenesis Ann Anat Pathol 237-246 in French 970688 Pott F Friedrichs H Huth F 1976a Results of animal experiments concerning the carcinogenic effect of fibrous dusts and their interpretation with regard to the carcinogenesis in humans] Zentralbl Bakteriol Orig B 467-505 in German 185852 Pott F Huth F Friedrichs KH 1974 Tumorigenic effect of fibrous dusts in experimental animals Environ Health Perspect 313 31d5oi 3428305 4377876 Rittinghausen S Kaspareit J 1998 Spontaneous cystic keratinizing epithelioma in the of Sprague rat Toxicol Pathol 298 30010.1177 lung a 9547872 019262339802600218 Rittinghausen S Mohr U Dungworth DL 1997 Pulmonary cystic keratinizing squamous cell lesions of rats after instillation of different particles Exp Toxicol Pathol 433 446. 9495643 Stanton MF Layard M Tegeris A et al 1981 Relation of particle dimension to in amphibole asbestoses and other fibrous minerals J Natl Cancer Instcar9ci6no5genicit9y75 6946253 Stenb^/ckF Rowlands J 1978 Role of talc and pyrene in respiratory tumor formation An experimental study Scand J Respir Dis 130-140 684384 Wagner JC Berry G Cooke TJ et al 1977 Animal experiments with talc In Walton McGovern B eds Inhaled Particles Vol IV Part 2 Oxford Pergamon Press WH 647- 654 pp Wehner AP Stuart BO Sanders CL 1979 Inhalation studies with Exp Tumor Res 177-198 538242 Syrian golden hamsters Prog Wehner AP Zwicker GM Cannon WC 1977 Inhalation of talc baby powder by hamsters Food Cosmet Toxicol 121-129 10.1016 S0015-6264 873404 TALC 391 4. Mechanistic and Other Relevant Data The general principles of inhalation deposition clearance soluble particles that have low and retention of poorly in this volume toxicity are discusssed in the Monograph on carbon black 4.1 4.1.1 Humans Deposition retention and clearance tissue Yao et al 1984 Clinically intrapleural instillation of pleural adhesions in cases of talc is used to induce & Antony 1997 pleural effusion and pneumothorax Rodriguez Churg and Wiggs 1985 used transmission electron dispersive ray spectroscopy to analyse the total fibrous microscopy and energy content of the lungs of a of 14 and fibrous mineral group male smokers who had lung cancer but no twofold higher respectively in the with group cancer than in the controls Kaolinite talc mica feldspars and crystalline silica fibrous comprised the majority of fibrous and non- particles in both groups In a subsequent study Churg and Wiggs 1987 examined the distribution of death and had a smoking history that ranged from 15 24 years The primary minerals identified to 100 years mean and accounted for 64 of the were kaolinite silica and mica respectively There fibres feldspars and talc accounted for 9 and % was a significant correlation between smoking history and particle concentration number of particles per gram of tissue in the diameters standard deviation upper lobes The SD of talc lobes were 0.9 ...mand 0.9 particles in the upper and lower ...mrespectively Dumortier et al 1989 used analytical electron fibrous particle content in the microscopy to examine non- bronchoalveolar lavage fluid of 51 occupationally 392 IARC MONOGRAPHS VOLUME 93 exposed subjects six of whom were talc millers In the latter almost exclusively talc in their lavage fluid while the group two workers had 40 chlorite In other others had about 60 talc and workers talc generally accounted for % of the particles in lavage fluid It was noted that although the exposure of one of the millers had 21 years before the examination talc particles were still present in his lavage fluciedased Talc particles have been found in stomach tumours from Japanese men Henderson et al 1975 possibly due to ingestion of treated rice 1971a Talc particles but apparently no other insoluble Merliss subserosal stroma of hernia particles were found in the talc is sacs possibly due to ingestion of medications in which a present as filler Pratt et al 1985 Anani et al 1987 reported the of talc fibres in the intestinal wall of a presence and year patient who had severe intestinal pain was diagnosed with intestinal talcosis A possible source of contained in oral medications exposure was the talc against tuberculosis which the patient had taken nearly 20 years earlier over a period of 22 months total intake of talc 183 g Talc is often present as a filler in some materials used of results in wide dissemination talc by drug addicts which particles to the lungs Groth et al 1972 Lamb & Roberts 1972 Farber et al 1981 Crouch & Churg 1983 spleen kidney liver brain heart adrenal and thyroid glands Groth et al 1972 and even the retina 1972 In the lungs most of the talc AtLee particles are found within the vessels of the alveolar walls and are almost invariably associated with marked granulomas Crouch & Churg 1983 The talc particles found in the foreign after intravenous injection than after inhalation lungs are larger Abraham & Brambilla 1980 see Section 4.1.2 for a discussion of the associated toxic effects In view of epidemiological evidence of a possible association between talc use for perineal hygiene and an increased risk for ovarian studies have been conducted in cancer see Section 2 several of women to determine potential retrograde movement particles through the reproductive tract to the ovaries These studies involved women who were about to undergo gynaecological surgery mostly for diseases complications of the reproductive tract and or with regard to healthy women may be limitedorgans Therefore broad interpretations of Egli and Newton 1961 found that inert carbon particles deposited in the in two of three patients travelled to the vagina fallopian tubes in about 30 minutes De Boer 1972 concluded that Indian ink deposited below the level the cervix is travel quickly through the reproductive tract In unlikely to Iturralde contrast the findings of Venter and 1979 and Mostafa et al 1985 suggested that retrograde transport to the fallopian tubes is possible Henderson et al 1971 reported the actual in histological specimens from 10 of 13 presence of talc and five of 12 ovarian tumours 12 of 21 cervical tumours normal ovarian tissues Subsequently Henderson et al Heller et al 1996 provided further evidence of the presence of talc in the1o9va7r9iesanodf women who had purportedly had perineal exposure to talc However in the latter study no relation was found between particle counts and talc reported perineal use of TALC 393 393 393 4.1.2 Toxic effects The toxic effects of talc in humans are dependent on the route and dose of administration and the physicochemical properties of the talc In commonly contain other addition talc products potentially toxic minerals see Section ) Talc pneumoconiosis is somewhat more prevalent and severe among people who are teaxlpcowsietdh to talc that contains asbestiform minerals than among those who are exposed to no such impurities Kleinfeld et al 1963 The form of this varies widely from a simple asymptomatic type Vallyathan & Craigphneeuamdoc1o9n8io1sitso disabling conglomerate pneumoconiosis Hunt 1956 Graham & Gaensler 1965 Miller et al 1971 Mixed pneumoconiosis is asbestosis and frequently seen including silicosis occasionally other forms Kleinfeld et al 1963 Mark et al 1979 Several early reports described talcum powder granuloma that arose from the talc on surgical gloves reviewed in Eiseman use of have documented et al 1947 Subsequent reports of cases pseudotumours a variety of surgical complications including adhesions and sinus tracts that were attributable to exposure to talc Lichtman et al 1946 Eiseman et al 1947 reviewed by Hollinger 1990 Both skin granulomas and talc pneumoconiosis have been reported after liberal use of talc on the body Tye et al 1966 Nam & Gracey 1972 Wells et al 1979 Tukiainen et al 1984 Wehner 1994 Respiratory distress syndrome which can be fatal has been described in children following massive accidental inhalation of talcum powder Cless & Anger 1954 Molnar et al 1962 Lund & Rasmussen 1969 Gould & Barnardo 1972 and in adult patients after talc pleurodesis Rehse et al 1999 A variety of pathological effects arise from the intravenous use by drug addicts of products that contain talc These include micronuclear pulmonary opacities Hopkins & Taylor 1970 Arnett et al 1976 Waller et al 1980 angiothrombotic hypertension Wendt et al 1964 Par^'et al 1979 Waller et al 1980 and conpgullommoenraartye pulmonary lesions Sieniewicz & Nidecker 1980 Crouch & Churg 1983 In addition retinopathy cerebral microembolization and granulomas of the liver lymph nodes and kidneys have been reported Min et al 1974 Par^'et al 1979 Carman 1985 A series of sectional studies reported from the New York State Labour Kleinfeld et al 1955 1963 1964 1973 have documented Department of in talc miners and talc pneumoconiosis millers especially among tremolitic talc workers The associated with pleural plaques restrictive or obstructive cases were decreased vital capacity of the lungs The prevalence of diseasebrweaasthliongwerdiasmorodnegrsthaonsde with lower cumulative exposure to dust and among those who processed granular rather than fibrous talc A series of sectional studies that described talc pneumoconiosis in workers in talc mining milling and manufacture in Italy Rubino et al 1963 Tronzano found that the prevalence was related to et al 1965 extent and duration of exposure and that talcs contaminated with tremolite serpentine and quartz were associated with pneumoconiosis significant 394 IARC MONOGRAPHS VOLUME 93 One representative controlled study among 80 workers exposed in the rubber industry to Vermont talc which is reported to have a low content of silica and fibres showed significantly increased respiratory symptoms impaired ventilatory function and increased respiratory morbidity but no radiographic abnormality Fine et al 1976 There has been some concern that talc may cause adult respiratory distress syndrome when instilled into the pleural space for pleurodesis Rinaldo et al 1983 Bouchama et al 1984 Kennedy et al 1994 Rehse et al 1999 Light 2000 Relatively recent cases were observed when talc was both insufflated and used as a slurry Brant & Eaton 2001 Scalzetti 2001 However other case series did not report the development of this disease Weissberg & Zeev 1993 Rodriguez & Antony 1997 Sahn 2000 Ferrer et al 2001 2002 Cardillo et al 2006 Many of the patients in the case reports had comorbid conditions The Working Group noted that the talc used in these reports was not always characterized mineralogically and may have contained contaminants ] The role of exposure to talc in the development of ovarian cancer has raised concerns see Section 2 The normal ovarian epithelium is known to express several mucins that are protective against epithelial inflammation and injury Lalani et al 1991 Gipson et al 1997 Ness & Cottreau 1999 Papadimitriou et al 1999 Ness et al 2000 La Vecchia 2001 Several epithelial cancers such as breast and ovarian cancer express mucin MUC which is upregulated and aberrantly glycosylated in many carcinomas Papadimitriou et al 1999 Cramer et al 2005 examined the association between the characteristics of women with no previous diagnosis of ovarian cancer and levels of antibodies to MUC a protein that is expressed by normal epithelial cells and overexpressed by ovarian cancer cells The study participants were 705 controls from a control study of ovarian cancer conducted in Massachusetts and New Hampshire USA between 1998 and 2003. Plasma specimens collected from participants at enrolment into the study were analysed for antiMUC antibody levels using an enzyme immunosorbent assay Forty cases of ovarian cancer with operative blood specimens were also included in additional analyses further 668 cases of ovarian cancer were included in the analyses to evaluate risk factors for ovarian cancer Multivariable logistic regression Spearman rank correlations and generalized linear models were used in the statistical analyses to determine which characteristics were associated with MUC antibody production and which were associated with the risk for ovarian cancer Women who reported no previous genital use of talc were more likely to have antibodies to MUC than women who a had history of regular genital exposure to talc 38.1 versus 28.6 P 0.04 In addition there was a borderline significant trend between frequency of talc use and lower MUC antibody levels P 0.11 after adjustment for other characteristics that affect antibody levels Several conditions associated with increased antibody production were associated with a decreased risk for ovarian cancer The authors concluded that these findings suggest that the presence of anti MUC1 antibodies is inversely correlated with risk for ovarian cancer Limitations of this study included the potential for bias in the participants recollection of their genital use of talc due to the control study design TALC 395 In addition antibody levels in the cases and controls may not be comparable since the presence of a cancer may affect anti MUC antibody levels] 4.2 Experimental systems 4.2.1 Deposition retention and clearance The deposition translocation and clearance of talc was investigated in 44 female golden Syrian hamsters 10 weeks of age that were exposed by nose inhalation for 2 hours to 40-75 mg activated talc Johnsons's Baby Powderfilot 228p median aerodynamic diameter 6.4-6.9 mThe powder was grade cosmetic talc and consisted of 95 w platy talc mineral Wehner et al 1977a Alveolar deposition was approximately 20-80 gwhich represented 6-8 of the inhaled amount The retention time of the talc deposited in the alveoli was 7-10 days and alveolar clearance was reported to be essentially complete 4 months after exposure No translocation of talc to liver kidneys ovaries or other parts of the body was found Wehner et al 1977b The Working Group noted that the unusually short clearance time may be related to limitations in the sensitivity of the detection methods and the large size of the particles used In rats exposed for 7.5 h per day on 5 days a week to aerosols of Italian talc mean concentration of respirable dust not further defined 10.8 mg the mean amounts of talc retained in the lung were 2.5 4.7 and 12.2 mg per animal following exposures for 3 6 and 12 months respectively These levels were approximately proportional to the cumulative exposures Wagner et al 1977 In rats exposed for 6 hours per day on 5 days a week for 4 weeks to 2.3 4.3 and 17 mg respirable talc the amounts retained in the lung at the end of exposure were 77 187 and 806 gtalc lung respectively Hanson et al 1985 Lung burdens of talc were determined in groups of 10 male and 10 female Fischer 344 rats and B6C3F mice following exposure to asbestos talc for 6 hours per day on 5 days a week for 4 weeks In rats exposed to 0 2.3 4.3 and 17 mg average lung burdens were 0 0.07 0.17 and 0.72 mg talc lung respectively In mice exposed to 0 2.2 5.7 and 20.4 mg average lung burdens of 0 0.10 0.29 and 1.0 mg talc lung respectively were observed When normalized to the exposure concentration the lung burden in mice was greater than that in rats and the normalized burden in rats increased with increasing exposure concentration Pickrell et al 1989 Conflicting data exist on systemic distribution following intrapleural instillation of talc i.e. talc pleurodesis in rats Following administration of 10 or 20 mg talc particle size unspecified to rats 20 per group talc was identified in the chest wall lungs heart brain spleen and kidneys The authors concluded that talc is rapidly absorbed through the pleura and reaches the systemic circulation and organs 24 hours after administration Werebe et al 1999 However following instillation of 40 mg talc median particle size 31 ...minto 33 rats randomly assigned to autopsy 24 or 72 hours later talc particles were 396 IARC MONOGRAPHS VOLUME 93 observed in only a few extrapulmonary organs i.e. the brain spleen and liver but not the kidneys Fraticelli et al 2002 The systemic distribution of talc was investigated in rabbits following talc pleurodesis in two studies In one study Ferrer et al 2002 10 rabbits received 200 mg bw um asbestos talc particles and 10 received 200 mg bw ...mtalc particles Five animals from each group were killed after 24 hours and five at 7 days after instillation A tendency was seen for increased extrapulmonary distribution of the smaller particles which were identified in the pericardium of 0/5 and 3/5 rabbits at 24 hours and 7 days respectively For the larger particles one of five animals had talc in the pericardium at each point Particles were identified in the liver of three of five animals exposed to the smaller particles 7 days after instillation other groups had no particles in the liver Small particles were found in the kidney of only 1/5 animals 24 hours after instillation Both particle types were found in the spleen of 1/5 animals 24 hours after instillation The results indicate that talc reached the lung parenchyma by breaking the mesothelial and elastic layer and that mobility was greater for the smaller particles In the other study Montes et al 2003 performed talc pleurodesis in rabbits 20 per group at doses of 50 and 200 mg bw of the particle talc used in the study by Ferrer et al 2002 Doses were chosen to simulate treatment of a kg patient with amounts of 3 and 12 g talc The lung parenchyma of two and 14 rabbits of the dose and dose groups respectively contained talc In the dose group six of the animals had tale in the pericardium and five had talc in the liver talc was not detected in these organs in the dose group The results show that the systemic distribution of talc was dependent In studies in rats mice guinea and hamsters that used radioactive tracer techniques no intestinal absorption or translocation of ingested tale to the liver or kidneys was detected Wehner et al 1977b Phillips et al 1978 No translocation of talc into the ovaries was detected after single or multiple intravaginal applications of talc to rabbits Phillips et al 1978 or monkeys Wehner et al 1985 1986 4.2.2 Toxic effects Reviews of the literature on the biological effects of talc in experimental animals are available Lord 1978 Wehner 1994 The Working Group noted that in most of the studies of talc described below no or limited characterization of the mineralogy of the sample employed was given and in particular information on fibre content or particle size was lacking ] a Chronic toxicity Mild to marked arterial endothelial cell proliferation with cellular encroachment into the lumen the occurrence of occasional foreign giant cells within the endothelial masses and moderate thickening of the alveolar septa of the lungs were observed TALC 397 after intravenous injections of talc in rabbits and guinea Puro et al 1966 Dogra al 1977 No effect on the rat lung was observed after intravenous injection of talc Schepers & Durkan 1955b but talc granulomas were seen in rats following intrasplenic injection of talc Eger & Canaliss 1964 No chronic pathological effect was associated with oral administration of Italian talc 92 pure 100 mg per day on 101 days over 5 months to rats Wagner et al 1977 Intratracheal injections of talc total dose 150 mg into guinea induced perivascular and peribronchiolar focal accumulations of histiocytes fibrocytes plasma cells and eosinophils within 1 month After 2 years the dominant effects were bronchiolectasia bronchiolitis and marked fibrosis Schepers & Durkan 1955b Rats exposed to dust clouds of 30-383 mg industrial or pharmaceutical talc for 9 months developed chronic inflammatory changes including thickening of the walls of the pulmonary arteries and eventually emphysema Iwa ska1971 In rats exposed by inhalation to 10.8 mg Italian talc grade 00000 ready milled mean particle size 25 ...mfor 3 months minimal fibrosis was observed the degree of which did not change during the observation period after exposure Animals that were exposed for 1 year had minimal to slight fibrosis the degree of which had increased to exposure moderate within 1 year after cessation of Wagner et al 1977 In contrast Syrian golden hamsters exposed to mg aerosols of cosmeticgrade talc for up to 150 minutes per day on 5 days a week for 30 days showed no histopathological changein the lungs heart liver renal tissues stomach or uterus Wehner et al 1977c Two years afterinjection of 20 mg Italian talc see above into the right pleural cavity of rats granulomas at the injection site were common and one small pulmonary adenoma was observed but no other relevant pathology was seen in the lungs Wagner et al 1977 Groups of male and female rats 6 w7eeks old were exposed to aerosols of 0 6 or 18 mg talc until mortalityin any exposure group reached % 113 weeks for males and 122 weeks for females These exposure concentrations provided a dose equivalent of 0 2.8 or 8.4 mg bw per day for male rats and 0 3.2 or 9.6 mg bw per day for female rats The talc used for this study was MP 10-52 Grade see Section 3.2.1 and was found to be free from asbestos by polarized light microscopy and transmission electron microscopy Survival of male and female rats was similar to that of the controls Mean body weights of rats exposed to 18 mg were slightly lower than those of controls after week 65. No clinical findings were attributed to exposure to talc Absolute and relative lung weights of male rats exposed to 18 mg were significantly greater than those of controls at the 6- 11- and month interim evaluations and at the end of the lifetime study while those of female rats exposed to 18 mg were significantly greater at the 11- 18- and month interim evaluations and at the end of the study Talc produced a spectrum of inflammatory reparative and proliferative processes in the lungs The principal toxic lesions observed included chronic granulomatous inflammation alveolar epithelial hyperplasia squamous metaplasia squamous cysts and interstitial fibrosis of the lung These lesions were accompanied by impaired pulmonary function characterized 398 IARC MONOGRAPHS VOLUME 93 primarily by reduced lung volumes reduced dynamic and quasistatic lung compliance reduced exchange efficiency and uniform intrapulmonary gas distribution National Toxicology Program 1993 Groups of male and female B6C3F mice 7 weeks of age were exposed by inhalation to aerosols that contained 0 6 or 18 mg MP 10-52 grade talc see Section 3.2.1 for up to 104 weeks dose equivalents 0 2 or 6 mg bw per day for male mice and 0 1.3 or 3.9 mg bw per day for female mice Survival and final mean body weights of male and female mice exposed to talc were similar to those of the controls No clinical findings were attributed to exposure to talc Inhalation exposure to talc was associated with chronic inflammation and accumulation of macrophages in the lung Accumulations of macrophages histiocytes containing talc particles were also observed in the bronchial lymph nodes National Toxicology Program 1993 b vitro toxicity A concentration 50 mL Italian talc caused a % reduction in the forming efficiency of cultured Chinese hamster V79-4 lung cells Chamberlain & Brown 1978 The concentration of talc 99 pure required to cause 50 haemolysis of red blood cells was 6.5 mL which is more than fold that of chrysotile A concentration of 0.1 mL talc caused 35 release of Cr from Syrian hamster tracheal epithelial cells labelled with radioactive sodium chromate the concentration was twofold that required for chrysotile Woodworth et al 1982 Davies et al 1983 examined the effect of different types of talc on mouse peritoneal macrophages in vitro Macrophages were exposed to seven specimens of purity tales and the release of lactate dehydrogenase and glucuronidase was measured These enzymes are produced by macrophages after they digest materials that can induce fibrosis and chronic inflammation Enzyme release after exposure of macrophages to quartz a known fibrogenic dust and magnetite a fibrogenic dust was also measured Quartz caused the greatest cytotoxic reaction in vitro the amount of enzyme released increased with the dose Magnetite had no effect All seven talc specimens were cytotoxic to the macrophages the levels of enzymes released were related but were lower than those observed after exposure to quartz The results show that tale is cytotoxic to macrophages and may be able to induce fibrosis and chronic inflammation in animals However the macrophage response to talc appears to be weaker than that for other fibrogenic dusts such as quartz and the response of macrophages to talc may be different in vivo Talc caused the release of several cytokines including X and C chemokines from normal human pleural mesothelial cells Nasreen et al 1998 Pleural mesothelial cells exposed to tale did not undergo apoptosis whereas malignant mesothelioma cell lines ATTC CRL 5820 5915 exposed to the same dose did Nasreen et al 2000 Talc also caused the release of basic fibroblast growth factor in pleural mesothelial cells Antony et al 2004 In bone marrow macrophages from mice talc was found to stimulate DNA synthesis thymidine incorporation Hamilton et al 2001 TALC 399 4.2.3 Genetic and related effects Three samples of respirable talc failed to elicit significant unscheduled DNA synthesis 10 20 and 50 cm24 hours sister chromatid exchange or aneuploidy 2 5 10 and 15 cm48 hours in rat pleural mesothelial cells in contrast to various positive controls The three samples i.e Spanish talc No. 5725 Italian tale No. 5726 and French talc No. 7841 contained 90-95 talc the remaining contents were chlorite and dolomite Electron microscopy analysis revealed that talc particles were taken up by the rat pleural mesothelial cells but no aneuploidy was observed in metaphases EndoCapron et al 1993 4.3 References Abraham JL Brambilla C 1980 Particle size for differentiation between inhalation and injection pulmonary talcosis Environ Res 94-96 0013-9351 90011-0 7389708 Anani PA Ribaux C Gardiol D 1987 Unusual intestinal talcosis Am J Surg Pathol 890 894. 00000478-198711000-00007 00000478-198711000-00007 3674285 Antony VB Nasreen N Mohammed KA et al 2004 Talc pleurodesis basic fibroblast growth factor mediates pleural fibrosis Chest 1522-1528 126.5.1522 15539722 Arnett EN Battle WE Russo JV Roberts WC 1976 Intravenous injection of containing drugs intended for oral use A cause of pulmonary granulomatosis and pulmonary hypertension Am J Med 711-718 0002-9343 1020758 AtLee WE Jr 1972 Talc and cornstarch emboli in eyes of drug abusers J Am Med Assoc 49-51 jama.219.1.49 5066587 Berner A Gylseth B Levy F 1981 Talc dust pneumoconiosis Acta Pathol Microbiol Scand A 17-21 7223423 Iwa skaJ 1971 Pathomorphological changes of respiratory system in experimental talcosis Med Pr 45-57 in Czech Bouchama A Chastre J Gaudichet A et al 1984 Acute pneumonitis with bilateral pleural effusion after talc pleurodesis Chest 795 797pneumoits chest.86.5.795 6488927 Brant A Eaton T 2001 Serious complications with talc slurry pleurodesis Respirology 181 185. j.1440-1843.2001.00327.x PMID 11555375 Cardillo G Carleo F Giunti R et al 2006 Videothoracoscopic talc poudrage in primary spontaneous pneumothorax a institution experience in 861 cases J Thorac Cardiovasc Surg 322 32j8.jtcvs.2005.10.025 PMID 16434260 Carman CR 1985 Talc retinopathy J Am Optom Assoc 129 1330980906 Chamberlain M Brown RC 1978 The cytotoxic effects of asbestos and other mineral dust in tissue culture cell lines Br J Exp Pathol 183 186956318 Churg A Wiggs B 1985 Mineral particles mineral fibers and lung cancer Environ Res 364-372 0013-9351 90117-3 4017991401791 400 IARC MONOGRAPHS VOLUME 93 Churg A Wiggs B 1987 Types numbers sizes and distribution of mineral particles in the lungs of urban male cigarette smokers Environ Res 121-129 10.1016 80013-0 3803330 Cless D Anger R 1954 Fatal asphyxia caused by aspiration of baby powder Kinderarztl Prax 506 50i8n German 14354807 Cramer DW Ernstoff L McKolanis JR et al 2005 Conditions associated with antibodies against the associated antigen MUC1 and their relationship to risk for ovarian cancer Cancer Epidemiol Biomarkers Prev 1125-1131 1055-9965.EPI 15894662 Crouch E Churg A 1983 Progressive massive fibrosis of the lung secondary to intravenous injection of talc A pathologic and mineralogic analysis Am J Clin Pathol 520 526 6624719 Davies R Skidmore JW Griffiths DM Moncrieff macrophages in vitro Food Chem Toxicol 201 6682083 CB 1983 Cytotoxicity of talc for 2007278-6915 90237-5 De Boer CH 1972 Transport of particulate matter through the human female genital tract J Reprod Fertil 295 29j7rf.0.0280295 5061985 Dogra RKS Iyer PKR Shanker R Zaidi SH 1977 Effect of talc injected intravenously in guinea pigs Toxicology 197 200 6 300-483X 857344 Dumortier P De Vuyst P Yernault JC 1989 fibrous inorganic particles in human bronchoalveolar lavage fluids Scanning Microsc 1207-1216 discussion 1217 1218 2561220 Eger W Canaliss DA 1964 On organ- especially liver changes after a single quartz- asbestosor talc injection into the portal circulation of rats Beitr Silikoseforsch Pneumokoniose 11-42 in German 14233950 Egli GE Newton M 1961 The transport of carbon particles in the human female reproductive tract Fertil Steril 151-155 13725928 Eiseman B Seelig MG Womack NA 1947 Talcum powder granuloma a frequent and serious postoperative complication Ann Surg 820-832 00000658-194711000- 00000658-194711000- 00015. 17859035 Capron S Renier A Janson X et al 1993 In vitro response of rat pleural mesothelial cells to talc samples in genotoxicity assays sister chromatid exchanges and DNA repair Toxicol In Vitro 7-14 0887-2333 20732166 Farber HW Fairman RP Glauser FL 1981 Bronchoalveolar lavage a new technique for the diagnosis of talc granulomatosis Abstract Chest 342 Ferrer J Villarino MA Tura JM et al 2001 Talc preparations used for pleurodesis vary markedly from one preparation to another Chest 1901-1905 119.6.1901 11399721 Ferrer J Montes JF Villarino MA et al 2002 Influence of particle size on extrapleural tale dissemination after talc slurry pleurodesis Chest 1018-1027 122.3.1018 12226049 Fine LJ Peters JM Burgess WA Di Berardinis LJ 1976 Studies of respiratory morbidity in rubber workers Part IV Respiratory morbidity in talc workers Arch Environ Health 195-- 200. 942261 TALC 401 Fraticelli A Robaglia A Riera H et al 2002 intrapleural administration an experimental study 122.5.1737 12426279 Distribution of calibrated talc after in rats Chest 1737-1741 Gipson IK Ho SB Michaud SJ et al 1997 Mucin genes expressed by human female reproductive tract epithelia Biol Reprod 999-1011 biolreprod56.4.999 9096884 Gould SR Barnardo DE 1972 Respiratory distress after talc inhalation Br J Dis Chest 230- 233. 0007-0971 90034-4 5044100 Graham WGB Gaensler EA 1965 silicosis in a rubber worker Med Thorac 590 604 4955721 Groth DH Mackay GR Crable JV Cochran TH 1972 Intravenous injection of talc in a narcotics addict Arch Pathol 171 1758046803 Gylseth B Stettler L G Mow^ et al 1984 A striking deposition of mineral particles in the lungs of a farmer a case report Am J Ind Med 231-240 ajim.4700060306 6475967 Hamilton JA McCarthy macrophage survival 11438042 G Whitty G 2001 Inflammatory microcrystals induce murine and DNA synthesis Arthritis Res 242-246 10.1186 Hanson RL Benson JM Henderson TR et al 1985 Method for determining the lung burden of talc in rats and mice after inhalation exposure to talc aerosols J Appl Toxicol 283 287 jat.2550050504 4056305 Heller DS Westhoff C Gordon RE Katz N 1996 The relationship between perineal cosmetic talc usage and ovarian talc particle burden Am J Obstet Gynecol 1507-1510 S0002-9378 9065129060 5120 Henderson WJ Joslin CA Turnbull AC Griffiths K 1971 Talc and carcinoma of the ovary and cervix J Obstet Gynaecol Br Commonw 266 2752558843 Henderson WJ Evans DMD Davies JD Griffiths K 1975 Analysis of particles in stomach tumours from Japanese males Environ Res 240-249 0013-9351 90004-3 1157802 Henderson WJ Hamilton TC Griffiths K 1979 Talc in normal and malignant ovarian tissue Lancet 499 S0140-6736 PMID Hollinger MA 1990 Pulmonary toxicity of inhaled and intravenous talc Toxicol Lett 121- 127 discussion 117-119 0378-4274 2198684 Hopkins GB Taylor DG 1970 Pulmonary tale granulomatosis A complication of drug abuse Am Rev Respir Dis 101 1054410600 Hunt AC 1956 Massive pulmonary fibrosis from the inhalation of talc Thorax 287 294 11.4.287 13391835 Kennedy L Rusch VW Strange C et al 1994 Pleurodesis using talc slurry Chest 342 346. chest.106.2.342 7774299 Kleinfeld M Messite J Tabershaw IR 1955 Talc pneumoconiosis Arch Ind Health 66 72 Kleinfeld M Giel CP Majeranowski JF Messite J 1963 Talc pneumoconiosis Arch Environ Health 101-115 14047558 Kleinfeld M Messite J Shapiro J et al 1964 Lung function in tale workers A comparative physiologic study of workers exposed to fibrous and granular talc dusts Arch Environ Health 559 56164195257 402 IARC MONOGRAPHS VOLUME 93 Kleinfeld M Messite J Langer AM 1973 A study of workers exposed to asbestiform minerals in commercial talc manufacture Environ Res 132-143 10.1016 0013-9351 90026- 1. 4713673 La Vecchia C 2001 Epidemiology of ovarian cancer a summary review Eur J Cancer Prev 125 12090008469-200104000-00002 PMID 11330452 Lalani EN Berdichevsky F Boshell M et al 1991 Expression of the gene coding for a human mucin in mouse mammary tumor cells can affect their tumorigenicity J Biol Chem 15420-15426 1714457 Lamb D Roberts G 1972 Starch and talc emboli in drug addicts lungs J Clin Pathol 876881. jcp.25.10.876 4566961 Langer AM Selikoff IJ Sastre A 1971 Chrysotile asbestos in the lungs of persons in New York City Arch Environ Health 348 3651100107 Lichtman AL McDonald JR Dixon CF Mann FC 1946 Talc granuloma Surg Gynecol Obstet 531-546 Light RW 2000 Talc should not be used for pleurodesis Am J Respir Crit Care Med 2024- 2026. 11112104 Lord GH 1978 The biological effects of talc in the experimental animal a literature review Food Cosmet Toxicol 51-57 S0015-6264 PMID 631664 Lund JS Rasmussen M 1969 Accidental aspiration of talc Report of a case in a year- old child Acta 5783418 Paediatr Scand 295 29610.1111 j.1651-2227.1969.tb04721.x j.1651-2 7.196.tb04721.x Mark GJ Monroe CB Kazemi H 1979 Mixed pneumoconiosis silicosis asbestosis talcosis and berylliosis Chest 726-728 75.6.726 436529 Merliss RR 1971a treated rice and Japanese stomach cancer Science 1141-1142 science.173.4002.1141 5098957 Merliss RR 1971b Talc and asbestos contaminant of rice J Am Med Assoc 2144 jama.216.13.2144d 5108683 Miller A Teirstein AS Bader ME et al 1971 Talc pneumoconiosis Significance of sublight microscopic mineral particles Am J Med 395 40d2oi 0002-9343 71 90229-4 5553956 Min W Gyorkey F Cain GD 1974 Talc granulomata in liver disease in narcotic addicts Arch Pathol 331 333531 335PMID 4416043 Molnar JJ Nathenson G Edberg S 1962 Fatal aspiration of talcum powder by a child Report of a case N EnJgMl ed 36-37 10.1056 NEJM196201042660110 NEJM1962010426010 14475255 Montes JF Ferrer J Villarino MA et al 2003 Influence of talc dose on extrapleural talc dissemination after talc pleurodesis Am J Respir Crit Care Med 348 355 rccm.200207-7670C 12773332 Mostafa SA Bargeron CB Flower RW et al 1985 Foreign body granulomas in normal ovaries Obstet Gynecol 701-702 3903583 Nam K Gracey DR 1972 Pulmonary talcosis from cosmetic talcum powder J Am Med Assoc 492-493 jama.221.5.492 5067955 Nasreen N Hartman DL Mohammed KA Antony VB 1998 induced expression of C and X chemokines and intercellular adhesion molecule in mesothelial cells Am J Respir Crit Care Med 971-978 PMID 9731033 TALC 403 Nasreen N Mohammed KA Dowling PA et al malignant mesothelioma cells in vitro Am 10673205 2000 Talc induces J Respir Crit Care apoptosis in human Med 595 600 National Toxicology Program 1993 Toxicology and Carcinogenesis Studies of Talc CAS No. 14807-96-6 in F344 Rats and B6C3F Mice Inhalation Studies Tech Rep Ser 421 Research Triangle Park NC Available at http://ntp.niehs.nih.gov/ntp/htdocs/LT_rpts/tr421.pdf htp:/ntp.niehs.nih.gov/ntp/htdocs/LT_rpts/tr421.pdf Ness RB Cottreau C 1999 Possible role of ovarian epithelial inflammation in ovarian cancer J Natl Cancer Inst 1459-1467 91.17.1459 PMID 10469746 Ness RB Grisso JA Cottreau C et al 2000 Factors related to inflammation of the ovarian epithelium and risk of ovarian cancer Epidemiology 111-117 00001648- 200003000-00006 PMID 11021606 Par^'JAP Fraser RG Hogg JC et al 1979 Pulmonary mainline granulomatosis talcosis of intravenous methadone abuse Medicine Baltimore 229 234949659 Phillips JC Young PJ Hardy K Gangolli SD 1978 Studies on the absorption and disposition of labelled talc in the rat mouse guinea and rabbit Food Cosmet Toxicol 161-163 S0015-6264 PMID 669513 Pickrell JA Snipes MB Benson JM et al 1989 Talc deposition and effects after 20 days of repeated inhalation exposure of rats and mice to talc Environ Res 233-245 S0013-9351 80069-6 2753008 Pooley FD 1976 An examination of the fibrous mineral content of asbestos lung tissue from the Canadian chrysotile mining industry Environ Res 281 29810.1016 90038-4 1001300 Pratt PC George MH Mastin JP Roggli VL 1985 Crystalline foreign particulate material in hernia sacs Hum Pathol 1141-1146 S0046-8177 4054893 Puro HE Wolf PL Skirgaudas J Vazquez J 1966 Experimental production of human blue velvet and red devil lesions J Am Med Assoc 1100-1102 197.13.1100 5953153 Rehse DH Aye RW Florence MG 1999 Respiratory failure following talc pleurodesis Am J Surg 437 44S 0 0002-9610 PMID 10365887 Rinaldo JE Owens GR Rogers RM 1983 Adult respiratory distress syndrome following intrapleural instillation of talc J Thorac Cardiovasc Surg 523-526 6834872 Rodriguez F Antony VB 1997 Pleurodesis state of the art Eur Respir J 1648 1654. 10.1183 09031936.97.10071648 9230261 Rubino GF Maranzana P Pettinati L Scansetti G 1963 pathological and clinical aspects of talc pneumoconiosis Med Lav 496-506 in Italian Sahn SA 2000 Talc should be used for pleurodesis Am J Respir Crit Care Med 2023- 2024 discussion 2026. 11112103 Scalzetti EM 2001 Unilateral pulmonary edema after talc pleurodesis J Thorac Imaging 99 102. 00005382-200104000-00006 PMID129212 11292212 Schepers GWH Durkan TM 1955a The effects of inhaled mining dust on the human lung Arch Ind Health 182 197 Schepers GWH Durkan TM 1955b An experimental study of the effects of talc dust on animal tissue Arch Ind Health 317 328 404 IARC MONOGRAPHS VOLUME 93 Seeler AO 1959 Talc pneumoconiosis N Me J Md ed 1084-1085 NEJM195911192612115 NEJM195911192612115 14444496 Sieniewicz DJ Nidecker AC 1980 Conglomerate pulmonary disease a form of talcosis in intravenous methadone abusers Am J Roentgenol 697 7062778101 Papadimitriou J Burchell J Miles DW Dalziel M 1999 MUCI and cancer Biochim Biophys Acta 301 31130571020 Tronzano L Coscia GC Capellaro F 1965 Exposure and risk in the process of grinding talc Med Lav 744 74i5n Italian Tukiainen P Nickels J Taskinen E Nyberg M 1984 Pulmonary granulomatous reaction talc pneumoconiosis or chronic sarcoidosis Br J Ind Med 84-87 PMID 6691939 Tye MJ Hashimoto K Fox F 1966 Talc granulomas of the skin J Am Med Assoc 1370- 1372. jama.198.13.1370 5953727 Vallyathan NV Craighead JE 1981 Pulmonary pathology in workers exposed to nonasbestiform talc Hum Pathol 28-35 S0046-8177 7203452 Venter PF Iturralde M 1979 Migration of a particulate radioactive tracer from the vagina to the peritoneal cavity and ovaries S Afr Med J 917-919 472930 Wagner JC Berry G Cooke TJ et al 1977 Animal experiments with talc In Walton WH McGovern B eds Inhaled Particles Vol IV Part 2 Oxford Pergamon Press pp 647- 654 Waller BF Brownlee WJ Roberts WC 1980 induced pulmonary granulomatosis consequence of intravenous injection of drugs intended for oral use Chest 90 chest.78.1.90 chest.78.1.90 7471850 A 94 Wehner AP 1994 Biological effects of cosmetic talc Food Chem Toxicol 1173 1184 0278-6915 7813991 Wehner AP Wilkerson CL Cannon WC et al 1977a Pulmonary deposition translocation and clearance of inhaled activated talc in hamsters Food Cosmet Toxicol 213 224 S0015-6264 892677 Wehner AP Tanner TM Buschbom RL 1977b Absorption of ingested talc by hamsters Food Cosmet Toxicol 453-455 S0015-6264 598798 Wehner AP Zwicker GM Cannon WC 1977c Inhalation of tale baby powder by hamsters Food Cosmet Toxicol 121-129 S0015- S015-624 S06012 5-6 624 64 80317-9 873404 Wehner AP Hall AS Weller RE et al 1985 Do particles translocate from the vagina to the oviducts and beyond Food Chem Toxicol 367 4040089 370 2 278-6 0278-6915 99 001 735 -0 Wehner AP Weller RE Lepel EA 1986 On talc translocation from the vagina to the oviducts and beyond Food Chem Toxicol 329 3380278-6915 90011-6 3525355 Weissberg D Zeev I 1993 Talc pleurodesis Experience with 360 patients J Thorac Cardiovasc Surg 689 6985412264 Wells IP Dubbins PA Whimster WF 1979 Pulmonary disease caused by the inhalation of cosmetic talcum powder Br J Radiol 586-588 0007-1285-52-619-586 465949 Wendt VE Puro HE Shapiro J et al 1964 Angiothrombotic pulmonary hypertension in addicts Blue velvet addiction J Am Med Assoc 755 75174122687 TALC 405 Werebe EC Pazetti R Milanez intrapleural administration 9925083 de Campos JR et in rats Chest al 1999 190 Systemic distribution of talc after 193chest.115.1.190 Woodworth CD Mossman BT Craighead JE 1982 Comparative effects of fibrous and nonfibrous minerals on cells and liposomes Environ Res 190 201 5 0.1016 90070-6 6279387 Yao Y Wang N Michel RP Poulsen RS 1984 Mineral dusts in lungs with scar or scar cancer Cancer 1814-1823 1097-0142 CNCR2820540909 6478417 406 IARC MONOGRAPHS VOLUME 93 5. Summary of Data Reported 5.1 Exposure data The term talc refers to both mineral talc and industrial mineral products that contain mineral talc in proportions that range from about 35 to almost 100 and are marketed under the name talc Mineral talc occurs naturally in many regions of the world where metamorphosed mafic and ultramafic rocks or magnesium carbonates occur Mineral talc is usually platy but may also occur as asbestiform fibres Asbestiform refers to a habit pattern of mineral growth and not to the presence of other minerals Asbestiform talc must not be confused with talc that contains asbestos Together with platy talc asbestiform talc is found in the Gouverneur District of New York State USA and occasionally elsewhere it may be associated with other minerals as observed by transmission electron microscopy Talc products vary in their particle size associated minerals and talc content depending on their source and application Minerals commonly found in talc products include chlorite and carbonate Less commonly talc products contain tremolite anthophyllite and serpentine Mineral talc is valued for its softness platyness inertness and ability to absorb organic matter It is used in agricultural products ceramics paint and other coatings paper plastics roofing rubber cosmetics and pharmaceuticals and for waste treatment Cosmetic talc which contains more than 90 mineral talc is present in many cosmetic products and is used for many purposes including baby powders and feminine hygiene products The type of talc that is currently used for cosmetic purposes in the USA does not contain detectable levels of amphibole including asbestos It is not known whether this is true in other countries Workers are exposed to talc during its mining and milling Reported geometric mean exposure levels to respirable dust are typically in the range of 1-5 mg Workers may also be exposed in user industries primarily in the rubber pulp and paper and ceramics industries Due to the presence of other particulates exposure levels may be difficult to measure accurately Consumer exposure by inhalation could occur during the use of loose powders that contain tale Accurate estimates of prevalence are not available However in some series of controls from epidemiological studies of ovarian cancer the prevalence of use for feminine hygiene of body powders baby powders talcum powders and deodorizing powders most of which contain cosmetic talc in varying amounts has been reported to be as high as 50 in some countries Perineal use for such purposes seems to have been a common practice in Australia Canada the United Kingdom the USA and other countries including Pakistan Use of cosmetic talc in the USA has declined steadily since the late 1970s TALC 407 5.2 Human carcinogenicity data The carcinogenic effect of exposure to talc not contaminated by asbestos fibres has been investigated in five independent but relatively small cohort studies of talc miners and millers in Austria France Italy Norway and the USA The miners and to a lesser extent the millers in these cohorts were also exposed to quartz In a control study nested in the combined cohorts of talc workers from Austria and France there was no tendency of higher risks for lung cancer by increasing cumulative exposure of workers to talc dust In four of five studies it was explicitly stated that no case of mesothelioma was observed In the two studies from Italy and Norway which included an estimate of cumulative exposure of the cohort to talc dust the risk for lung cancer in the highest category was found to be close to or below unity In the subgroup of miners in the study in the USA an excess risk for lung cancer was found which may be have been due to exposure in the workplace to radon daughters and quartz In all the other groups of workers studied there was no increased risk for lung cancer Female workers in the Norwegian pulp and paper industry had an increased risk for ovarian cancer which however was attributed to exposure to asbestos A communitybased control study did not find an increased risk for ovarian cancer associated with occupational exposure to talc but the prevalence of exposure was low Body powder containing talc has been used by women on the perineum or genital area on sanitary napkins and on diaphragms In total data from one prospective cohort study and 19 control studies were reviewed in the evaluation of the association of cosmetic talc use and the risk for ovarian cancer The information collected on perineal talc use varied substantially by study e.g. ever use versus regular use and whether information on the mode of application frequency or duration of use was available The cohort study was conducted among nurses in the USA and included 307 cases of ovarian cancer that occurred over 900 000 person of observation and a maximum of 14 years of follow Information was collected on the frequency but not duration of regular use Perineal use of talc was not associated with a risk for ovarian cancer The 20 control studies were conducted in Australia Canada China Greece Israel Norway the United Kingdom and the USA nested control study and included between 77 and 824 cases and 46 and 1367 controls Five were hospital designs and the others were population studies The Working Group designated a subset of these studies as being more informative based on the following characteristics the study was population was of a reasonable size had acceptable participation rates and included information to allow control for potentially important confounders Eight population control studies from Australia Canada Ontario and the USA two overlapping studies in Boston MA and one each in California Delaware Valley eastern Massachusetts and New Hampshire and Washington State were thereby identified as being more informative The selected studies included at least 188 cases and had participation rates that generally ranged from 60 to 75 Among these eight studies the prevalence of use of body powder among controls ranged from 16 to 52 however 408 IARC MONOGRAPHS VOLUME 93 information on exposure was not collected in a comparable manner across studies In addition the frequency and duration of use or total lifetime applications were investigated in several studies as well as consideration of prior tubal ligation or simple hysterectomy Only sparse data were available on whether women had used body powder before or after the 1970s The relative risks for ovarian cancer among users of body powder versus users were homogenous across this relatively diverse set of eight studies each of which indicated a 30 6i0ncrease in risk Among the other 11 control studies most also reported relative risks of this magnitude or higher The subset of studies that assessed use of talc on a diaphragm were relatively uninformative due to their lack of precision Results on exposure relationships were presented in the cohort study and in seven of the more informative control studies In the cohort study no exposure- response trend was apparent Positive exposure trends were apparent in the two Boston studies that presented the most comprehensive analysis In the Canadian and Californian studies a significant weakly positive trend was observed for either duration or frequency of use but not for both In the other three control studies no consistent trend was observed and the strongest associations tended to be seen among the shorter or less frequent talc users The cohort study and four of the eight more informative control studies presented results on histological type of ovarian cancer When the analysis of the cohort study was restricted to the 160 serous invasive cases a statistically significant increase in risk of about 40 was observed The risk increased with increasing frequency of body powder use Risks for serous ovarian cancer were somewhat greater than those for other histological types in two of the four control studies in which the contrast was reported Results for other histological types were inconclusive The Working Group carefully weighed the various limitations and biases that could have influenced these findings differential misclassification of talc use given the relatively crude definitions available would have attenuated any true association Although the available information on potential confounders varied by study most investigators accounted for age oral contraceptive use and parity In most studies only the adjusted relative risks were presented however in the three studies in which both age- adjusted and fully adjusted estimates were provided relative risks did not differ materially suggesting minimal residual confounding It is possible that confounding by unrecognized risk factors may have distorted the results One or more such factors if they are causes of ovarian cancer and also associated in the population with perineal use of talc could induce the appearance of an association between the use of talc and ovarian cancer where there is none In order for such an unrecognized risk factor to induce the consistent pattern of excess risks in all of the casecontrol studies it would be necessary for the factor to be associated with perineal talc use across different countries and different decades While the range of countries and decades covered by the more informative control studies is not very broad it provides some TALC 409 diversity of social and cultural context and thereby reduces the likelihood of a hidden confounder There was a distinct pattern of excess risk discernible in all of the control studies when users were compared with users however methodological factors needed to be considered First while chance cannot be ruled out as an explanation it seemed very unlikely to be responsible for the consistent pattern of excess risks A second possible explanation would be recall bias to which control studies may be particularly susceptible This may have been the case if there had been widespread publicity about the possible association between the use of body powder and cancer In such circumstances it is possible that women who had ovarian cancer could be more likely than women who did not to remember or report a habit such as body powder use if they thought that it may have played a role in their illness There was a flurry of publicity in the USA in the 1970s concerning the possible risks for cancer posed by the use of based body powders Following an industry decision to market talc powders with no asbestos it was the opinion of the Working Group that there had not been widespread public concern about this issue at least until very recently Therefore the Working Group considered it unlikely that such a bias could explain the set of consistent findings that stretch over two decades The Working Group believed that recall bias was a possibility inherent in the control studies and could not be ruled out The Working Group also considered publication and selection biases and these were not judged to have substantially influenced the pattern of findings The Working Group searched for documentation on the presence of known hazardous minerals in based body powders There were strong indications that these products contained quartz in the 1970s and still do There were also indications that occasional small concentrations of asbestos were present in these products before the 1970s but the available information was sparse sampling methods and detection limits were not described and the range of locations where data were available was extremely limited As a result the Working Group found it difficult to identify a date before which based body powders contained other hazardous minerals and after which they did not or to have confidence that this would be applicable worldwide In addition the epidemiological studies generally do not provide information about the years during which the female subjects were exposed Consequently the Working Group could not identify studies in which an uncontaminated form of talc was the only one used by study subjects Nevertheless the Working Group noted that even in the most recent studies in the USA where exposure histories may have been much less affected by hazardous contaminants of talc the risk estimates were not different from the early studies in which the possibility of such exposure was more likely To evaluate the evidence on whether perineal use of talc causes an increased risk for ovarian cancer the Working Group noted the following The eight more informative control studies as well as most of the less informative ones provided overall estimates of excess risk that were remarkably consistent seven of these eight control studies examined exposure 410 IARC MONOGRAPHS VOLUME 93 relationships two provided evidence supporting such a relationship two provided mixed evidence and three did not support an association The cohort study neither supports nor strongly refutes the evidence from the case- control studies control studies were susceptible to recall bias which could tend to inflate risk estimates but to an unknown degree All of the studies were susceptible to other potential biases which could either increase or decrease the association * All of the studies involved some degree of differential misclassification of exposure that would tend to underestimate any true underlying association 5.3 Animal carcinogenicity data Talc of different grades was tested for carcinogenicity in mice by inhalation exposure intrathoracic intraperitoneal and subcutaneous injection in rats by inhalation exposure intrathoracic injection intraperitoneal injection oral administration and intrapleural and ovarian implantation and in hamsters by inhalation exposure and intratracheal injection In male and female rats exposed by inhalation to a defined talc the incidence of bronchiolar carcinoma or adenoma and carcinoma combined was significantly increased in female rats The incidence of adrenal medulla pheochromocytomas benign malignant or complex combined showed a significant positive trend and the incidence in dose males and females was significantly greater than that in controls The incidence of malignant pheochromocytomas was also increased in dose females The Working Group did not consider it probable that the increased incidence of pheochromocytomas was causally related to talc but based on the experimental data available neither could related effects be excluded Tumour incidence was not increased following the intrapleural or intrathoracic administration of a single dose of various talcs to rats In two studies of intraperitoneal administration in rats no increase in the incidence of mesotheliomas was observed No increased incidence of tumours was produced in rats in two studies of talc administered in the diet or in another study of the implantation of talc on to the ovary Tumour incidence was not increased in mice following the inhalation of talc in one study the intrathoracic administration of a single dose of various tales in another study or the administration of talc by intraperitoneal injections in three studies A single subcutaneous injection of talc into mice did not produce local tumours Tumour incidence was not increased following inhalation or intratracheal administration of talc to hamsters 5.4 Mechanistic considerations and other relevant data Different mechanisms are probably operative in the effects of talc on the lung and pleura depending on the route of exposure TALC 411 In humans deposition retention and clearance of talc have been insufficiently studied although talc particles have been found at autopsy in the lungs of talc workers In humans and experimental animals the effects of talc are dependent on the route of exposure and the dose and properties of the talc Talc pneumoconiosis was somewhat more prevalent and severe among miners exposed to talc containing asbestiform minerals and asbestos than among those exposed to talc without such contaminants However the role of quartz and asbestos in the observed pneumoconiosis could not be ruled out Among drug users intravenous injection of talc present as a filler in the drugs resulted in microembolization in a variety of organs and alterations in pulmonary function In animal studies talc has been shown to cause granulomas and mild inflammation when inhaled Observations of the effects that occurred in the lungs of rats exposed by inhalation to talc suggested that the operative mechanisms may be similar to those identified for carbon black and talc is known to cause the release of cytokines chemokines and growth factors from pleural mesothelial cells In humans intrapleural administration of talc as a therapeutic procedure results in pleural inflammation which leads to pleural fibrosis and symphysis Pleural fibrosis is the intended effect of intrapleural administration of talc in patients with malignant pleural effusions or pneumothorax Animal studies suggested that extrapulmonary transport of talc following pleurodesis increases with decreasing particle size and increasing administered dose Talc has been shown to cause apoptosis of malignant cells in vitro Perineal exposure to cosmetic talc in women is of concern because of its possible association with ovarian cancer Several studies have been conducted in women to assess potential retrograde movement of particles through the reproductive tract to the ovaries These have been conducted in women who were about to undergo gynaecological surgery most of whom had diseases or complications of the reproductive tract and organs that required surgery The findings reported in these studies may be confounded by the various levels of dysfunction in clearance from the female reproductive tract due to underlying pathologies In addition most of the studies had little or no further information on the use of talc products for perineal hygiene or changes in habits that may have preceded surgery On balance the Working Group believed that the evidence for retrograde transport of talc to the ovaries in normal women is weak In women with impaired clearance function some evidence of retrograde transport was found Studies in animals rodents langomorphs and human primates showed no evidence of retrograde transport of tale to the ovaries In one study predictors of the presence of antibodies to mucin protein were inversely related to the risk for ovarian cancer and exposure to powder containing talc No data were available on the genotoxic effects of exposure to talc in humans The limited number of studies available on the genetic toxicology of talc in vitro gave negative results 412 IARC MONOGRAPHS VOLUME 93 6. Evaluation and Rationale 6.1 Cancer in humans There is inadequate evidence in humans for the carcinogenicity of inhaled talc not containing asbestos or asbestiform fibres There is limited evidence in humans for the carcinogenicity of perineal use of talcbased body powder 6.2 Cancer in experimental animals There is limited evidence in experimental animals for the carcinogenicity of talc not containing asbestos or asbestiform fibres 6.3 Overall evaluation Perineal use of based body powder is possibly carcinogenic to humans Group 2B Inhaled talc not containing asbestos or asbestiform fibres is not classifiable as to its carcinogenicity Group 3 6.4 Rationale In making this evaluation the Working Group considered the human and animal evidence as well as evidence regarding the potential mechanisms through which tale might cause cancer in humans The Working Group found little or inconsistent evidence of an increased risk for cancer in the studies of workers occupationally exposed to talc The studies of talc miners and millers were considered to provide the best source of evidence but no consistent pattern was seen One study observed an excess risk for lung cancer among miners but confounding from exposure to other carcinogens made it difficult to attribute this to tale and no excess risk was seen in millers Other studies also found no increased cancer risk or no higher risk with increasing cumulative exposure Overall these results led the Working Group to conclude that there was inadequate evidence from epidemiological studies to assess whether inhaled talc not containing asbestos or asbestiform fibres causes cancer in humans For perineal use of based body powder many control studies of ovarian cancer found a modest but unusually consistent excess in risk although the impact of bias and potential confounding could not be ruled out In addition the evidence regarding exposure was inconsistent and the one cohort study did not provide support for an association between talc use and ovarian cancer Concern was also expressed that TALC 413 exposure was defined in a variety of ways and that some substances called talc may have contained quartz and other potentially carcinogenic materials A small number of Working Group members considered the evidence to be inadequate Despite these reservations the Working Group concluded that the epidemiological studies taken together provide limited evidence of an association between perineal use of based body powder and an increased risk for ovarian cancer In one study of rats that inhaled talc an excess incidence of malignant lung tumours was seen in females The same study observed an excess incidence of pheochromocytomas in the adrenal medulla in both sexes but the Working Group was divided as to whether these rare tumours could be attributed to exposure to talc Other studies in rats and mice using different routes of administration did not find an excess of cancer and two studies in rats were considered to be inadequate for evaluation Based on the one positive study the Working Group found that there was limited evidence of carcinogenicity of inhaled talc in experimental animals There was no agreement within the Working Group as to whether the evidence on pheochromocytomas should be taken into account in the evaluation of animal data