Document VJZdYx5BbKp98vp2D4z4j8e24

FILE NAME: Talc (TALC) DATE: 1973 Feb DOC#: TALC011 DOCUMENT DESCRIPTION: Medical Journal Article - Talc- A Possible Occupational and Environmental Carcinogen IIS ' Talc: A Possible Occupational and Environmental Carcinogen Hector P. Blejer, M.D., D.l.H. and Robert Arlon, Pharm. D. I ale is mineralogically closely related to three of the five major asbestos group minerals, specifically, the serpentine Chrysotile, as wejl as the first two of the amphiboles Anthophyllife, Tremolite, Amosite and Crocidolite. In certain toxicological' aspects, .talc and asbestos are also closely related- They are silicates which produce fibrosis of the lung and other tissues. Talcs and the asbestos minerals cited are hydrous magnesium silicates difficult to dif ferentiate-- except w ith special techniques such as electron microscopy with selected area diffraction-- and which form in the same as well as sim ilar geological processes. Con sequently, many talc deposits contain asbestos minerals, so that in industrial and commercial1use, .such talcs always contain varying Amounts of asbestos .fibers. Because of this asbestos con tamination of talcs, we reviewed data on: (1) The composition of talc and related asbestos minerals; (2) The toxic effects of both substances; (3) The general environmental exposures to talc; and (4) Its common uses, including those involving ingestion of talccontaining foods and drugs. Ad ditionally, (3) Mineral residues from talc-coated rice washings were analyzed for asbestos. Then we re-evaluated such data, together with new findings on the asbestos contamination of talc-coated polished white rice. As a result, we Dr Biejer is Medical 'Officer and Head, O c cupational Health, Southern California Bureau of O c cupational Health and Environmental Epidemiology, State of California Department of Public Health, Los Angeles, and Assistant Clinical Professor of Medicine, School of Medicine, University of Southern Califor nia, Los Angeles Dr Arlon-is from Kaiser Foundation Hospitals, Los Angeles Rep rint request*; to 1449 Te m p le St, Sui*e 106, lo s Angeles 90026 (Dr. Blejer). Presented in part at the 15th annual Western In dustrial Health Conference, San Francisco, October 1, 1971 92 present some new ' conclusions about than a mineral species: It includes all related possible health risks arising from gradations, from' the pure mineral to im occupational and environmental ex posures to asbestos contaminated talcs. pure massive talcose rocks, such as soapstone. In fact, some commercial talc deposits can contain a very small talc content with varying amounts of many Definitions and Composition of , accessory minerals, such as asbestos, Talc quartz, and other "impurities." In the Pure talc and the three related .United States, for example, the Saint asbestos group minerals are hydrous Lawrence County, New York State com magnesium silicates whose theoretical mercial talc deposits contain 30% or less chemical formulae are: of mineralogically pure talc The remain der consists partly of: (1) Serpentine, the True Talc Anthophyilile Asbestos Mgs Si Orn (OH)-i Mg? Sis O 22 (O H )? host mineral of chrysotile, antigorite and lizardite; (2) Trem olite; and An- Chrysotile Asbestos Mgs Su Oio (O H )s thophyllite,- which can convert naturally Tremolite Asbestos Ca2 Mgs Sis O 22 (OH) 2 to talc. Although mineralogical "im Mineralogically, there are two forms of purities," the asbestos minerals are con talc- Nonasbestiform, also called platy or sidered in many cases as an integral part nonfibrous, and Fibrous, also called of such commercial talc, whereas other trem olitic. As used com m ercially, however, the term "talc" connotes cer m ineralogical im purities, such as hematite and pyrite, are commercially tain desired physical properties rather unacceptable 1 An example is that talcs - - La b ia 1. -- Observed and Expected D eaths, B y C ause - Among 632 Asbestos In sulatio n W orkers Observed Pro sp ectively S Jan u ary 1S 43 -- 30 June 1371* - ' '" - . - - Cause of De3ch Total, Ail Causes - Deaths Number Observed Expected 418 232 1 Ratio Observed to Expected "Percent Observed 1.5 100.0 - ' Teta) Cancer (Ail Sites) - 1S7 . _ Cancer of the Lung. Pleura Trachea, Bronchus S2 Lung Cancer- ? , ^. , - 35 ' Pleural Mesothelioma - _ 7 Peritoneal MesctheJicma ' 19 --- -Cancar of Stomach, Colon, Rectum . 41 ; Cancer ct All Other Sites ' 35 51.6 3.6 - 44.7 ` - . - . ' i l . l 8.3 - 7 7 ' f ' -- ' 12.4 3.3 " . 26.1 ' '1.2 22.0 ` ' 20 3 - ' " 1.7 ` 45 ` 9.8 - . 8.4 _ Asbestosis - 32 - ' - 7.7 = ' Aif Other Causes, ' . 199 . 230.5 ' 0.9 47 6 " ' * Source Selikoff et a t 6 7 ' US data not ailaWe, but figure should be only slightly less than 11 I . -r US data not available, but these are rare causes'of death in the general population. . . ' .- : ; ` 1;/-' ' - .- '7 'C : Table 2. -- Deaths End Expected fetoriaiity from Cancer of the Lung and Pleura and Gastrointestinal-Tract - and Peritoneum Related to Age in Talc Workers* / Age ' . Group . ' Tota! Deaths -- ' Y Less tlien-40 - T ' . 91 2 40 55 -. 38 % 60 ,79 - 80 an d'O ver . ' ' . ' 47 - 4 : Deaths From - . Proportional fi/iortalityT '/ . Malignant Causes i Lung and Pleura _ G i t and Peiitonsuni " - Lung and Pleure G K and Peritoneum Observed Theoretical Observed-' Theoretical/ . 10 ' ' - 0 ' , 2- s ; - o 7 ; 0. 2 - 4 1 - 11 ' 0 5.3 17 . . " 0. .3 .2 ' -' , 5.5 3.9 ' : V - '.V ' 7 .7 5.35 ^ 0 . . 5.3 ' . . 5.5 _ 8.5 . 6.95 ' 25 :. ; 4 .3 f * After Kleinfeld et a l.s t Number of deaths in a group divided by total deaths in same group x 100 4 Gastrointestinal tract. Difference not statistically significant. II Difference statistically significant (p = < 0 .0 1). <[ Statistical analysis not done due to small number in group. for milling are often chosen preferen tially on the basis of how much "Im purity" is present, apparently because talc with larger, purer gialns is more dif ficult to mill. Also of note is that the most recent revision of the US Phar macopeia2 does not specifically exclude asbestos as an impurity In its definition of pharmaceutical grade talc. The World Health Organization3 in its 1971 re evaluation of food additives noted that asbestos is a contaminant in some talcs. All of these are factors which make.it im perative to ascertain the mineralogical type and purity of talcs in assessing their potential health effects. Toxic Effects Asbestos. -- Different forms of asbestos appear to have different biological effects. These differences are still too incompletely understood and complex to be discussed here, except as mentioned briefly below. Nevertheless, it can be stated that carcinogenicity is the most serious toxic effect of the various asbestos group minerals. In the last few decades in particular, these substances, especially some types of crocidolite, have been occupationally associated with greatly excessive incidence of pleural and peritoneal mesotheliomas, previously extremely infrequent cancers in humans.4 Moreover, a number of researchers have experimentally induced pleural mesotheliomas after intrapleural Injection of various forms of asbestos and dem onstrated the neoplastic nature of those tumors.5 As shown in Table 1, Selikoff et al6 recently reported that among a cohort cf 632 asbestos in sulation workers, of the 418 deaths ob served from January 1, 1943, to June 30, . 1971, 20% were due to bronchogenic carcinoma, 10% to cancer of the stomach, colon, and rectum, and 6% to pleuial and peritoneal mesothelioma. The asbestos forms used In the past by these workers were mostly chrysotile and amosite, w ith possibly small amounts of crocidolite. As a group, the same asbestos in sulation workers show about eight times an excess mortality from bronchogenic carcinoma. Moreover, asbestos in sulation workers who smoke have a 92 fold risk of dying from bronchogenic car cinoma, as compared with men who neither smoke nor work with asbestos.7 Thus, this type of occupational asbestos inhalation exposure points to another ef fect of asbestos, that of a cocarcinogen. The asbestos group minerals have the added toxic effect of fibrogenicity which results in: Asbestosis, the well-known occupational lung fibrosis due to chronic inhalation overexposure; Pleural plaques and calcifications, as well as the less w ell-known asbestos corns or "warts" of the skin among workers handling such materials. As mentioned, toxicological effects of different forms of asbestos appear to be different. For example, as compared with chrysotile, exposure to the amphiboies is generally more likely to produce asbestosis and bronchogenic carcinoma. Also, Inhalation of crocidolite-- es pecially of some types with shorter, finer fib e rs as m e a su re d by e le c tro n microscopy-- appears to produce more mesotheliomas than other amphiboies and chrysotile. This subject was reviewed recently and succinctly by Wagner.8 In addition, inhaled asbestos particles retained in lung tissues can be covered with a proteinaceous-iron coating which produces a type of ferruginous body commonly termed "asbestos body." Talc. -- As shown in Table 2, Klein feld et al9 demonstrated that talc miners and millers in Northern New York State have 3.4 times an excess mortality from lung and pleural carcinomas. Such ex cess was shown to be statistically significant and appeared 20 years later than among asbestos insulation workers. The New York investigators ascribed this' difference, in part, to talc being less car cinogenic than asbestos, without con sidering the fact that talc deposits in the northern part of that state contain much asbestos, as we noted above. No significant difference was found be tween the observed and expected mor tality from carcinoma of the gastroin testinal tract and peritoneum among these talc workers 9 A w ell-know n effect of talcs, especially the fibrous variety, is talcosis, another of the many occupational lung fibroses. Other toxic effects are the production of granulomas in wounds and scars, and intense mesothelial irritation, with fibrosis and adhesion in the pleural and peritoneal cavities. These occurred often in the past, due to the operated tissues being contaminated with the talc used as dusting powder for and shed from surgical gloves-- a use no longer recommended.10 Likely for similar reasons, the Kaiser Foundation Hospital in Los Angeles discontinued the use of "talcum" powders for any inpatient use. A bizarre, new and serious talc effect is that of pulm onary intravascular granulomas with vascular thrombosis and sclerosis leading to pulmonary hypertension, due to intravenous in jection of talc-containing oral tablets and talc-adulterated substances in drug misuse.11 Inhaled fibrous talc particles can also be changed by cells in the lung into another type of ferruginous body which some call "talc bodies." Hygienic Work Standards Asbestos. -- For 1972, the Committee on Threshold Lim t Values for Airborne Contaminants of the American Con ference of Governmental Industrial Journal of Occupational Medicine/Vol. 15, No. 2/February 1973 93 Hygienists (A C CIH ) has proposed a tirpe-welglqted, average limit value (for an 8-hour workday, 40-hour workweek) for all forms of asbestos of 5 fibers per milliliter longer than 5 )t in length, as determined by the membrane filter method at 430-times magnification phase-contrast illu m in a tio n .12 This Threshold Limit Value (TLV) has been developed as the air concentration of asbestos fibers which (1) should afford protection against asbestosis, and (2) reduce to an acceptably low risk the development of neoplasms. This TLV does not assure complete elimination of the carcinogenic risk because of in complete understanding of dose-effect relationships. Moreover, even though different forms of asbestos appear to have different toxic effects, a single TLV was established for all forms because of incomplete information about these dif ferences.13 In June 1972, a similarly documented but lower Time-Weighted Average (TWA) of two such fibers-- proposed earlier In the year by the National in stitute for Occupational Safety and Health, Public Health Service, US De partment of Health, Education, and Welfare-- was adopted for all forms of asbestos, effective July 1, 1976, by the Occupational Safety and Health Ad ministration (O SH A ), US Department of Labor. Until that effective date, the 5fiber TWA discussed above applies as the US standard for all forms of asbestos14 It should be noted that all these stand ards are based on the identification and quantification of all forms and types of asbestos fiber by phase-contrast (op tical) microscopy. Although evidence about their toxic effects is still not well understood, certain chrysotile, crocidolite, and other asbestos fibers are too short and/or fine to be detected ex cept by electron microscopy. Essentially the same can be said of chrysotile fibrils-- ultramicroscopic morphological units of a chrysotile fiber mentioned in the section on Environmental Exposures and illustrated In the Figure. Talc. -- For 1972, the ACGIH has a TLV for each form of talc:12 (a) Nonasbestiform Talc 20 million par ticles per cubic foot of air (mppcf), based on the Light-field dust count. (b) Fibrous Talc: The same TLV of 5 fibers discussed above. The Documentation for these TLV's takes into account the different biological ef fects of the two forms of talc and of the need to determine their type and purity.13 The revised Table G-3-- Mineral Dusts In the same OSHA standards cited15 lists only one hygienic work standard of 20 mppcf for talc. This Is an error which should be rectified. Otherwise, the 20 mppcf applies as the US Federal Stand ard for both platy and fibrous talc. Environmental Exposures to Talc T a lc is e c o lo g ic a lly v ir tu a lly ubiquitous through its many uses in modern living. Only very recently has Electronphotornicrographs of particles extracted from talc-coated rice. Left: Talc (T ) and Am phibole asbestos (A ) fibers. Right: Talc fiber (T ) with Chrysotile asbestos fibril ( C ) . Identification confirm ed with selected area dif fraction. (Electron microscopic studies by D r. A . M . Langer, Hew York. Original magnification X 45,0 0 0 .) ) -r : 94 Talc: A Possible Occupational and Environmental Carnnogen/Biejer and Arlor, < there, been some indication of its widespread environmental inhalation and other exposures to humans As reported in 1972, Langer el al16 set out through electron microscopy to identify asbestos materials in the lungs of 28 consecutive autopsy cases of New York City residents. Asbestos bodies were found in only three cases, whereas chiysotile fibers were present in 24. Moreover, chrysotile fibrils were found in all 28 cases. In addition, clay and/or talc particles were identified in the lungs of 18 of these 28 decedents, all of whom had been long-time residents of that city. None had been asbestos workers nor, from our review of the published data, talc workers. Recently, Henderson et al17 drew attention to the close association of talc and asbestos minerals when, searching for asbestos through special electron microscopic techniques, they unexpectedly identified talc particles deeply imbedded within the tissue of primary ovarian, endometrial and cer vical carcinomas. Table 3 summarizes these data and also shows that no talc particles were found in the one secon dary ovarian carcinoma thus studied. Additionally, the same investigators found talc particles also in " normal" ovarian tissues removed from' patients with breast cancer. They made no com ment, however, as to how the talc par ticles reached the ovaries and other reproductive tissues in which the talc was found; nor did they comment as to Table - " 4 . -- Tele Used in the United S ta te s *? - and Sold or Used in California 1953-1963 Averager " 1 : Table 3 . -- Tafc Particles Foun in Selecied ^ K o r m a f' ' and Cancerous Fem ale Eeprudticiivc T is su e s * - Specimen - ` .. Number Primary Tumor ' Ovary -- . 35 - . Cervix - - ' ' ?! Endometrium* ' Secondary Tumor _ - - ' -- Ovary* ' - " N o rm a r Ovary From Patient - With Breast Cancer - - '. ; ' 1 ' 1 - . ' ' t .2 . ' * Source Henderson et al 17 t Particle size range. 1000 A = 5 urn t Same patient ,, _Talc Foundr " . Number . - - Percent ' 23 ' _ . \ ' ' - ID ' , ' 12 " ? -1- r ` 66 ' 77 - ' , 57 . too . . o . 6' -> " - 5 .'y.'-; " 0 -, : ' . whether the presence of talc was ad ventitious or causative. A different study reported in mid-1971 by the Environm ental Sciences Laboratory, Mt. Sinai School of Medicine, The City University of New York, revealed that significant amounts of asbestos were present in two brands of commercial, household-use fibrous talc dusting ("talcum ") powder. As a result, the US Food and Drug Ad ministration announced that if such results were to be corroborated by an in dependent expert panel, it would ask the manufacturers to recall such "talcum" powders It is of inteiest that in dependent geologists informed the FDA that talc and asbestos can appear in the same mines, and that contamination could be caused at that source.18 18 Uses of Talc G en e ral. -- Talc is found in cosmetics; spray and dusting powder, including "talcum "; chalks and crayons; ceramics; electric and heating insulating materials, roofing materials, insecticides, foundry' facings; textiles; white shoe polishes and glove cleaners. Talc is also used as pigment in paints, varnishes, and rubber, filler for asphalt, paper, rubber, plastic, and soap; dusting powder in rubber manufacturing, and products such as inflatable toy ballons, prophylac tic condom s, and contraceptive diaphragms1 10 In Foods and Drugs. -- Talc also en ters into food processing and phar maceuticals. It is used as an excipient and filler for pills and tablets, for dusting tablet molds; in clarifying liquids by ' Use * - . _ /.To ta l - . ' Ceramics . . Z Paints - - - Rubber ?-~ Insecticides - . Paper . Roofing - V , Toilet Preparations Textiles - .V ? ` Asphalt Filler . - J * Foundry Facings . Refractories - - -Rice Coating ' ' Crayons Other Uses Percent - United States California 100 100 38 60 21 21 5 - 3 4 - 2 ' 4 2 , 7 __ . 2 ' 2 - 2 4' - _ . : 2 4 -` - ' 4 * 4 ' 2 ' 4 _ 15 8 ` 1963 US consumption- 763 x 103 short tons t Source: Weils 1 4 Less than 1 percent Area and Ethnic Group Japan' California'! issei? Nisei Black White Table 5 . -- fige-Standardized Death Rates for M alignant Kec-plasms of the Stom ach, by S e x, Japan and Various Ethnic Groups in California Rate Male Female Male,-'Female 68.6 3b 5 1.9 29 9 13.0 2.3 1 1 .7 11.3 1.0 14.6 49 30 8.0 4.0 2.0 ' 1964-1965. Source. Segi et a l.22 < 1957 1964 for issei and Nisei; 1959 1961 for Black and White. Source. Dunn and Buell.76 ' Foreign born Japanese. US-born Japanese. Journal of Occupational Medicine/Vol. 15, No. 2/February 1973 vironmenlal and consumer health risks Environmentally produced deposition and retention of talc particles in human lungs appear to be widespread. Also, talc particles have been found in some normal ovaries, as in the core of primary cancers of the ovary, endometrium, and cervix of nonoccupationally talc- or asbestos-exposed wom en in Britain. Nevertheless, the presence of talc in these tissues cannot presently be said to be more than adventitious, and a finding whose significance must aw ait corroboration by well-controlled studies, preferably from diverse geographical areas. Moreover, many talc dusting ("talcum ") powders and Californiaprocessed talc-coaled rices recently tested were found to contain significant amounts of asbestos. Such findings raise questions of possible world-wide in creased health risks to humans, arising from occupational and environmental exposures to those every-day use cosmetics, foods, drugs, and other products which contain talcs signifi cantly contaminated with asbestos. It is not the intent here to imply that all forms of talc pose an occupational or environm ental carcinogenic risk, although there are obvious instances in which certain talcs can be a source of asbestos exposure. The data presented here indicate that whenever talc ex posures are expected to occur, adequate analyses be done beforehand to deter mine that mineral's type and purity, as well as the related need for proper oc cupational and environmental controls. This approach is warranted because, in our experience, many exposed em ployees and consumers at large consider working with or using talc-containing materials essentially safe, which has not been the universal occupational ex perience. Although there is no scientific evidence of any carcinogenicity of talc per se, we would be remiss if we did not suggest a need for feasible, properly con trolled experimental animal exposure studies to ascertain any possible car cinogenicity of pure talc. The authors thank Ors A. M Langer and I J. Selikoff, Ml Sinai School of M edicine, New York, for their constructive comments and assistance; Ms Marilyn Hunter and the Communication Service Cen ter, California Department of Public Health, Berkeley, for their painstaking work on manuscript preparation, the Reference Staff, Public Health Library', University of California, Berkeley, and Mr E Hughes, Medical Librarian, Kaiser Foundation Hospital, Los Angeles, for their indispensible help in researching the literature. References 1. W ells )R: Talc, soapstone, and pyrophyllile, in Mineral Facts and Problems, 1965 ed US Bureau of Mines, US Govern ment Printing Office, 1965, pp 919-927. 2. The United Slates Pharmacopeia, 18th revision. US Pharmacopeial Convention, Inc, 1965, p 708. 3. World Health Oigamzation Technical Report Series, No. 462 Evaluation of Food Additives. Geneva, 1971, p 16. 4 Wagner |C, Sleggs CA, Marchand P: Dif fuse pleural mesothelioma and asbestos ex posure in the North Western Cape Province. Brit I Industr Med 17 260-271, 1960 5. Smith W E, Miller L, Churg |, et al Mesotheliomas in hamsters following in trapleural iniection of asbestos. ] Mount Sinai Hosp N Y 32-1-8, 1965. 6. Selikoff l|, Hammond EC, Churg |- Mor tality experience of asbestos insulation workers, 1912-1971 Presented at the IV In ternational Conference on Pneumonconiosis, Bucharest, Sept 29, 1971. 7. Selikoff Ij, Hammond EC, Churg I Asbestos exposure, smoking, and neoplasia. IAMA 204 106-112, 1968 8. Wagner ]C Cunent opinions on the asbestos cancer problem Ann O ccup Hyg 15.61-64, 1972 9 Kleinfeld M, Messite I, Kooyman O , et al. Mortality among talc miners and millers in New York State Arch Environ Health 14 663 667, 1967. 10. Merck Index, ed 8. 1968, p 1011. 11. Hopkins C B, Taylor C D Pulmonary talc granulomatosis. Amer Rev Resp Dts 101 104, 1970 12 American Conference of Governmental Industrial Hygienists Threshold Limit Values of Airborne Contaminants and Physical Agents with Intended Changes Adopted by AC CIH for 1972 Cine nnah, 1972 13 American Conference of Governmental Industrial Hygienists- Documentation of 'he Threshold Limit Values for Substances in Workroom Air, ed 3. Cincinnati, 1971 14 US Office of the Federal Register O c cupational safety and health standards. Title 29 -- Labor, Chap XVII, Section 1910.93a, as of lune 7, 1972, p 11130. 15. US Office of the Federal Register- Table G-3 -- Mineral Dusts, Section 1910 93, 1972, p 11230 16. Langer AM , Selikoff II, Sastre A- Chrysotile asbestos in Ihe lungs of persons in New York City. Arch Environ Health 22 348 361, 1971 17. Hendeison W), Jos 11n CAF, Turnbull AC, et al- Talc and carcinoma of the ovary and cervix. I Obstet Cynaec But Comm 78 266 272, 1971 18. Trade and government memos, in F-D-C Reports 33.1, luly 12, 1971 19. Trade and government memos, in E-D-C Reports 33.12, July 19, 1971 20. Feirel RE, Kohler C O , Mickus RR New rice coaling materials Rice I 69 11, 1966 21. Houslon DF, Kohler G O : Nutritional Properties of Rice Washington, National Academy of Sciences, 1970 , 22. Segi M, Kurihara M, Matsuyama T. Can cer Mortality For Selected Sites in Twenty-four Countries, No 5 (196^--1965) Sendai, lapan, Dept of Public Healih, Tohoku University School of Medicine, 1969. 23 Doll R, Payne P, Waterhouse I (eds) Cancer Incidence m Five Continents A Technical Report. International Union Against Cancer, Berlin, Springer-Veilag, 1970, vol 2 24 Merliss RR Talc-treated rice and lapanese stomach cancer Science 173 1141 1142, 1971. 25. Wynder EL, Kmel I, Dungal N, el al An epidemiological inves igalion of gastric can cer. Cancer 16 1461-1496, 1963 26. Dunn |E Jr, Buell PE- Gastro-intestinal cancer among the ethnic groups in California Epidemiology of Gastrointestinal Cancer Sym posium, Proceedings of the Third World Congress of Gaslioenterology. Recent A d vances in Castroenteiology 1:35-47, 1967. Journal of Occupational Medicine/Vol. 15, No. 2/February 1973 97