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FILE NAME Talc TALC DATE 1973 Feb DOC TALC011 DOCUMENT DESCRIPTION Medical Journal Article - Talc- A Possible Occupational and Environmental Carcinogen Talc A Possible Occupational and Environmental Hector P. Blejer M.D. D.I.H. and Robert Arlon Pharm D. Carcinogen Talc related to is mineralogically closely three of the five major about conclusions present some new related possible health risks arising from than a mineral species It includes all gradations from the pure mineral to im- asbestos group minerals specifically the occupational and environmental ex- pure massive talcose rocks such as serpentine Chrysotile as well as the first posures to asbestos contaminated talcs soapstone In fact some commercial talc two of the amphiboles Anthophyllite Tremolite Amosite and Crocidolite In deposits can contain a very small talc content with varying amounts of many 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- Definitions Talc and Composition of. accessory minerals such as asbestos quartz and other impurities In the Pure talc and the three related .United States for example the Saint asbestos group minerals are hydrous magnesium silicates whose theoretical chemical formulae are Lawrence County New York State com- . mercial talc deposits contain 30 or less of mineralogically pure talc The remain- ferentiate with special der consists partly of 1 Serpentine the techniques such as ^'lectron microscopy True Talc Mg6 S18 020 OH host mineral of chrysotile antigorite and with selected Ee thophyllite which form in area diffraction the same as well as Anthophyllite Asbestos Chrysotile Asbestos Mg7 Sia O22 OH Mg6 S14 010 OH lizardite 2 Tremolite and Anwhich can convert naturally similar geological processes Con- Tremolite Asbestos Ca2 Mgs S18 O22 OH to talc Although mineralogical im- vues sequently many talc deposits contain asbestos minerals so that in industrial Mineralogically there are two forms of talc Nonasbestiform also called platy or purities the asbestos minerals are considered in many cases as an integral part MIN and commercial use such talcs always nonfibrous and Fibrous also called of such commercial talc whereas other EMR contain varying amounts of asbestos tremolitic As used commercially mineralogical impurities such as do fibers Because of this asbestos con- however the term talc connotes cer- hematite and pyrite are commercially tamination of talcs we reviewed data tain desired physical properties rather unacceptable ' An example is that talcs 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 Additionally 5 Mineral residues from coated rice washings were analyzed for asbestos Then we evaluated such Table 1. - Observed and Expected Deaths By Cause Prospectively Among 632 Asbestos Insulation Workers Observed 1 January 1943 - 30 June 1971 Cause of Death Total All Causes ~~ Deaths Number Observed Expected 418 2321 Rado Observed to Expected . Percent Observed 1.5 100.0 data together with new findings on the __ asbestos contamination of coated polished white rice As a result we Dr Blejer is Medical Officer and Head Oc cupational Health Southern California Bureau of Oc- * Total CanAlcl eSitres Cancer of the Lung Pleura 187 Trachea Bronchus Lung Cancer- rn 2 Pleural Mesothelioma ~ : Peritoneal Mesothelioma 51.6 oo 92 35 : 7 19 11.1 i 3.6 . RETTSE RETTSE RETTSE RETTSE | 44.7 an ~ 22.0 20 ; * 1.7 _ 45 cupational Health and Environmental Epidemiology State of California Department of Public Health Los Angeles and Assistant Clinical Professor of Medicine ~ Cancer of Stomach Colon Rectum - Cancer of All Other Sites ~ 7 41 ~ 35 12.4 RETTSE 28.1 RETTSE 9.8 - 8.4 -2 : Asbestosis a School of Medicine University of Southern Califor- _ nia Los Angeles Dr Arlon from Kaiser Foundation _ aren Hospitals Los Angeles four Reprint requests to 1449 Temple St Suite 106 Los All Other Causes 2 32 199 $ 230.5 _ ~ 0.9 7.1 47 Angeles 90026 Dr. Blejer Presented in part at the 15th annual Western In- Source Selikoff et al 6 7 dustrial Health Conference San Francisco October Malet 1 1971 * US data not available but figure should be only slightly less than 111 * * US data not available but these are rare causes of death in the general population aDani 92 enoSaat Table 2 Deaths and Expected Mortality from Cancer of the Lung and Pleura and GastrointestiTrnaaclt and Peritoneum Related to Age in Talc Workers - Age Group Group : ~ Total Deaths Total 91 Less than > 2 40-59 40-59 38 Deaths From Malignant Causes Proportional Mortality = Lung and Pleura G and Peritoneum ~- || Lung and | Glf and | Pleura | Peritoneum | Observed | Theoretical 10 9 2s 7 7 -f 0 o2 11 0 5.3 3.2 a ] 5 5.5 . | Observed 7.7 . : Theoreticalfi 5.3 . | 5.37 5.5 7 80 and Over ee oe aL on eee Ceres 25 4.3 * After Kleinfeld et al + Number of deaths in a group divided by total deaths in same group x 100 * Gastrointestinal tract Difference not statistically significant 11 Difference statistically significant p = < 0.01 Statistical analysis not done due to small number in group for milling are often chosen preferentially on the basis of how much impurity is present apparently because talc with larger purer grains is more dif- ficult to mill Also of note is that the most recent revision of the US Phar- macopeiadoes not specifically exclude asbestos as an impurity in its definition of pharmaceutical grade talc The World Health Organization in its 1971 re- evaluation of food additives noted that asbestos is a contaminant in some talcs All of these are factors which makeit im- perative to ascertain the mineralogical type and purity of talcs in assessing their potential health effects sulation workers of the 418 deaths observed from January 1 1943 to June 30 . 1971 20 were due to bronchogenic carcinoma 10 to cancer of the stomach colon and rectum and % to pleural and peritoneal mesothelioma The asbestos forms used in the past by these workers were mostly chrysotile and amosite with 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 carcinoma as compared with men who neither smoke nor work with asbestos.7 Toxic Effects - Thus this type of occupational asbestos Asbestos Different forms of asbestos appear to have different Inhalation exposure points to another effect of asbestos that of a cocarcinogen biological effects These differences are The asbestos group minerals have the still too incompletely understood and added toxic effect of fibrogenicity which complex to be discussed here except as results in Asbestosis the known mentioned briefly below Nevertheless it occupational lung fibrosis due to can be stated that carcinogenicity is the chronic inhalation overexposure Pleural most serious toxic effect of the various plaques and calcifications as well as the asbestos group minerals In the last few decades in particular these substances especially some types of crocidolite less known asbestos corns or warts of the skin among workers handling such materials have been occupationally associated As mentioned toxicological effects of with greatly excessive incidence of different forms of asbestos appear to be pleural and peritoneal mesotheliomas different For example as compared with previously extremely infrequent cancers chrysotile exposure to the amphiboles is in humans.4 Moreover a number of generally more likely to produce researchers have experimentally induced asbestosis and bronchogenic carcinoma pleural mesotheliomas after intrapleural injection of various forms of asbestos and demonstrated the neoplastic nature Also inhalation of crocidolite pecially of some types with shorter finer fibers as measured by electron of those tumors As shown in Table 1 microscopy to produce more Selikoff et al recently reported that mesotheliomas than other amphiboles among a cohort of 632 asbestos in- 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 coating which produces a type of ferruginous body commonly termed asbestos body Talc - As shown in Table 2 Kleinfeld et al ,,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 these talc workers 9 among A known 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 use no longer recommended 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 pulmonary intravascular granulomas with vascular thrombosis and sclerosis leading to pulmonary hypertension due to intravenous injection of containing oral tablets and 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 Values for Airborne Contaminants of the American Conference of Governmental Industrial Journal of Occupational Medicine 15 No. February 1973 93 Hygienists ACGIH has proposed a weighted average limit value for an hour workday hour workweek for all forms of asbestos of 5 fibers per milliliter longer than 5 ... in length as determined by the membrane filter method at times magnification contrast illumination 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 incomplete understanding of 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 Weighted Average TWA of two such proposed earlier in the year by the National Institute for Occupational Safety and Health Public Health Service US Department of Health Education and Welfare adopted for all forms of asbestos effective July 1 1976 by the Occupational Safety and Health Administration OSHA US Department of Labor Until that effective date the 5- fiber TWA discussed above applies as the US standard for all forms of asbestos 14 and illustrated in the Figure Talc - For 1972 the ACGIH has a TLV for each form of talc a Nonasbestiform Talc 20 million particles per cubic foot of air mppcf based on the Light 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 effects of the two forins of talc and of the need to determine their type and It should be noted that all these standards are based on the identification and quantification of all forms and types of asbestos fiber by contrast optical microscopy Although evidence about their toxic effects is still not well understood certain chrysotile crocidolite and other asbestos fibers are too short and fine to be detected ex- purity.1puri3ty.13 The revised Table Mineral Dusts in the same OSHA standards cited 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 Standard for both platy and fibrous talc cept by electron microscopy Essentially the same can be said of chrysotile ultramicroscopic morphological units of a chrysotile fiber mentioned in the section on Environmental Exposures Environmental Exposures to Talc Talc is ecologically virtually ubiquitous through its many uses in modern living Only very recently has Electronphotomicrographs of particles extracted from coated rice Left Talc T and Amphibole asbestos A fibers Right Talc fiber T with Chrysotile asbestos fibril C Identification confirmed with selected area diffraction Electron microscopic studies by Dr. A. M. Langer New York Original magnification X 45,000 ae 94 e there been some Indication of its widespread environmental inhalation and other exposures to humans As reported in 1972 Langer et al 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 chrysotile fibers were present in 24 Moreover chrysotile fibrils were found in all 28 cases In addition clay and talc particles were identified in the lungs of 18 of these 28 decedents all of whom had been 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 cervical 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 comment 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 . Talc Used in the United - States and Sold or Used in California 7 1959-1963 Average Table 3. Talc Parcles Found in Selected <2 5 | yt. = ~ - and Cancerous Female Reproductive Tissues Specimen - ~ Primary Tumor Ovary Cervix Endometrium - _ . _ . oo Secondary Tumor Ovary _ 7 - er ne - Normal Ovary from Patient - With Breast Cancer 2-0 _; Cole - .12 " Source Henderson et al 17 + Particle size range 1000 A = 5 um * Same patient a 4 2 1 - a . _ Talc Foundr Number 7 0 23 ; 10 12 _ pvadees-P 4 . - Percent 66 : 77 fo, 57 7 100 ; || 0 a 0 : 0- 0 : : a = whether the presence of talc was adventitious or causative A different study reported in 1971 by the Environmental 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 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 interest 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 19 Uses of Talc General Talc is found in cosmetics spray and dusting powder including talcurn 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 prophylactic condoms 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 ae Use - - - Total _ Ceramics 2 Paints Rubber Insecticides a ~~ Paper Roofing 7 Toilet Preparations = Textiles Asphalt Filler - Foundry Facings Refractories Rice Coating Crayons Other Uses Percent . : United States | California 100 38 21 5 4 4 7 2 2 - 22 "ee $ ? $ 100 60 | 21 3 2 2 _ 2 to a0 _~ - 2 - 15 8 * 1963 US consumption 763 x 10 short tons Source Wells ' + Less than 1 percent Area and Ethnic Group Japan Californiat Issei Nisei Black White Table 5. - Standardized Death Rates for Malignant Neoplasms of the Stomach by Sex Japan and Various Ethnic Groups in California Male 68.6 Rate Fernale 355 Female 1.9 299 13.0 ; 2.3 11.7 11.3 1.0 . 14.6 49 30 : : 8.0 4.0 2.0 * 1964-1965 Source Segi et al.22 * 1957 1964 for Issei and Nisei 1959 1961 for Black and White Source Dunn and Buell.26 * Foreign born Japanese born Japanese Journal of Occupational Medicine 15 No. February 1973 95 vironmental 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 women 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 await corroboration by controlled studies preferably from diverse areas Moreover many geographical talc dusting talcum powders and Californiaprocessed coated rices recently tested were found to contain significant amounts of asbestos Such findings raise questions of possible world increased health risks to humans arising from occupational and environmental exposures to those every use cosmetics foods drugs and other products which contain talcs significantly contaminated with asbestos It is not the intent here to imply that all forms of talc pose an occupational or environmental 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 determine 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 employees and consumers at large consider working with or using containing materials essentially safe which has not been the universal occupational experience Although there is no scientific evidence of any carcinogenicity of talc pesrewe would be remiss if we did not suggest a need for feasible properly controlled experimental animal exposure studies to ascertain any possible carcinogenicity of pure talc The authors thank Drs A. M Langer and 1 J. Selikoff Mt Sinai School of Medicine 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 Libranan for their literature Kaiser Foundation Hospital Los Angeles indispensible help in researching the References 1. Wells R Talc soapstone and pyrophyllite in Mineral Facts and Problems 1965 ed US Bureau of Mines US Govern- ment Printing Office 1965 pp 919-927 2. The United States Pharmacopeia 18th revision US Pharmacopeial Convention Inc 1965 p 708 3. World Health Organization Technical Report Series No. 462 Evaluation of Food Additives Geneva 1971 p 16 4 Wagner JC Sleggs CA Marchand P Diffuse pleural mesothelioma and asbestos exposure in the North Western Cape Province Brit | Industr Med 17-260-271 1960 5. Smith WE Miller L Churg , et al Mesotheliomas 117 hamsters following intrapleural injection of asbestos / Mount Sinai Hosp NY 1-8 1965 6. Selikoff IJ Hammond EC Churg | Mortality experience of asbestos insulation workers 1912-1971 Presented at the IV In- ternational Conference on Pneumonconiosis Bucharest Sept 29 1971 7. Selikoff ) Hammond EC Churg I Asbestos exposure smoking and neoplasia JAMA 204 106-112 1968 8. Wagner JC Current asbestos cancer problem opinions on the Ann Occup Hyg 15.61-64 1972 9 Kleinfeld M Messite , 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 GB Taylor GD Pulmonary talc granulomatosis Amer Rev Resp Dis 101 104 1970 12 American Conference of Governmental Industrial Hygienists Threshold Limit Values of Airborne Contaminants and Physical Agents with Intended Changes Adopted by ACGIH for 1972 Cincinnati Cincinnati 1972 13 American Conference of Governmental Industrial Hygienists Documentation of the Threshold Limit Values for Substances in Workroom Air ed 3. Cincinnati 1971 14 US Office of the Federal Register Oc- cupational safety and health standards Title 29- 29- Labor Chap XVII Section 1910.93a as of June 7 1972 p 11230 15. US Office of the Federal Register Table G 3- Mineral Dusts Section 1910 93 1972 p 11230 16. Langer AM Chrysotile asbestos in New York City Arch Selikoff II Sastre A the lungs of persons in Environ Health 348- 361 1971 17. Henderson W Joslin CAF Turnbull AC et al Talc and carcinoma of the ovary and cervix | Obstet Gynaec But Comm 78 266- 272 1971 18. Trade and government memos in D Reports 33.1 July 12 1971 19. Trade and government memos in D Reports 33.12 July 19 1971 20. Ferrel RE Kohler GO Mickus RR New rice coating materials Rice / 69 11 1966 21. Houston DF Kohler GO 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 Countries No 5 1964-1965 Sendai Japan Dept of Public Health Tohoku University School of Medicine 1969 23 Doll R Payne P Waterhouse | eds Cancer Incidence in Five Continents A Technical Report International Union Against Cancer Berlin Springer 1970 vol 2 24 Merliss RR treated rice and Japanese stomach cancer Science 173 1141- 1142 1971 25. Wynder EL Kmet , Dungal epidemiological inves igation of cer Cancer 16 1461-1496 1963 N et al An gastric can- 26. Dunn JE Jr Buell PE intestinal cancer among the ethnic groups in California Epidemiology of Gastrointestinal Cancer Symposium Proceedings of the Third World Congress of Gastroenterology Recent Advances in Gastroenterology 35-47 1967 97 Journal of Occupational Medicine 15 No. February 1973