Document ZnY196X127XvJwMONz0YgOB6d

PLAINTIFFS EXHIBIT ASA-149 L.J. Cralley, Ph. D., M.M. Key, M. D., I). II. (irulh,M.D. W.S. Lainharl, At. D., and It. M. Ligo,M. D. * Reports of finding pulmonary fibrous bodies, previously referred to as "asbestos" and now as "ferruginous" bodies, in the lungs of persons coming to autopsy in hospitals in a number of cities have recently been increasing. The first report of these morphologically distinctive fibrous bodies in the sputum and lungs of asbestos workers was made in 1906 by Marchand (1). Current interest dates from 1963 when Thompson et al. found these fibrous bodies in the lungs in 26. of the autopsies in a series of examinations in Cape Town (2). Subsequent investigations (3-8) provide evidence that the occurrence of these bodies in the lungs of urban residents is not restricted to those in isolated localities and is not a one-time chance observation. The if v The fibers were r J - ----i J : ....s bn the basis of their morphological structure. In searching for the sources of these ubiquitous fibers, Cralley et al. (9) reported that t 1 *U.S. Department of Health, Education and Welfare Public Health Service National Center for Urban and Industrial Health Occupational Health Program 1014 Broadway, Cincinnati, Ohio 45202 Presented at the American Industrial Hygiene Conference May 13-17, 1968. Preprinted by permission of The American Industrial Hygiene Association Journal. i \ I HER 0000747 l -2And was a potential source of the ferruginous bodies observed in the lungs of humans. This observation led to further study to characterize cosmetic talcum products. The major purpose of the investigation reported here was to develop and present data on some of the constituents found in cosmetic talcum products and to discuss their health aspects in the light of today's knowledge. It is not our intent to make a general appraisal of health factors in the use of talcum products because of the many variables involved and the limited data available on the consumption of various "sources of talcs" in the formu lation and use of cosmetic talcum products. The potential health aspects of some of the data, however, are discussed. Twenty-two cosmetic talcum products (representing body powder, bath powder, and all purpose powder) purchased off-the-shelf, were analyzed for fibrous content, selected metals, and quartz. The data and a discussion of their possible significance follow. Analysis of Talcum Products Talc is a natural mineral, hydrous magnesium silicate, with the general formula (OH^MggS^O^Q. Talc mineral is formed by the hydrothermal alteration of serpentine and tremolite or directly from unserpentinized ultrabasic rocks. Talc may also be formed by the thermal meta morphism of silicous dolomites (10-12). The characteristics of the mineral \ HER 0000748 -3- deposits vary widely from the pure tale formula and from each other according to the mineralogy involved, r----- - ' ! ,r-r:--------- iW.it'LK.l -.-.Vr.-' w` ----------- " ' - ... 1r other basic material from which the talc may be derived. The deposits may also y- * ah. ___... ...I:'.:-.. . - --11 -j: ::TCosmetic talcum may be basically pure talc or may be a formulation of talc with other materials such as clay, chalk, stearates, etc. Zinc, titanium, manganese, and iron compounds may be added as pigments and opacifiers. The particle-size distribution and per cent by count of fibers in the talcum particulates were determined by dispersing the talcum in water, filtering the mixture through an "AAU membrane filter, and measuring with a phase contrast microscope at 430 magnification. The per cent of free silica was determined by X-ray diffraction. Cobalt, chromium, nickel, and manganese were determined by means of atomic absorption spectro photometry. Zirconium, titanium, zinc, iron, and magnesium were deter mined by means of semi-quantitative emission spectrography. Table I gives analytical data on 22 different cosmetic talcum products. Size Distribution of Talcum Particulates Seven of the twenty-two talcum products were selected for size- distribution measurements of the fibrous and non-fibrous particulate com ponents. lI \ 1 HER 0000749 ] -4in these samples The diameter of SO to 95% of all the particulatcs/was under 5. 0 microns ( u). The median of the diameter of the non-fibrous particulates in the seven products ranged from 0.7 to 2.0 jn, with a median average around 1. 0 u. / A fiber is defined as a particulate having at least a 1:3 ratio of diameter to length. The fibrous particulates in the seven products were generally under 1. 0,u in diameter, with lengths ranging from 1.5 to 6. 0 u. The 22 talcum products analyzed showed fiber contents ranging from 8 to 30% by count of the total talcum particulates with an average of 19%. Although the specific fibrous materials were not identified, they were pre dominantly fibrous talc, as shown by X-ray diffraction, with the probable presence in minor amounts of other fibrous minerals such as tremolite, anthophylite, chrysotile, and pyrophyllite. The electron microscope, with its higher power of resolution, shows a number of submicron diameter particulates not visible by means of phase contrast microscopy* as-indicated-ia-the-accompanying-electron.phot&micr.-graphs. Free Silica In 8 of the 22 talcum products (Table I), the presence of quartz ranged from 0.3 to 1. 0%; in 13 products, 1.2 to 3.0% quartz, and in 1 product, 54.4% quartz. \ , her 0000750 -5Metals With the exception of talcum products No. 4, 8, and 22 (Table I), the cobalt content of the products analyzed was under 25 parts per million (ppm), chromium under 22 ppm, nickel under 29 ppm, and manganese under 78 ppm. Product No.4 had a nickel content of 1270 ppm; chromium 340 ppm; ( and cobalt, 67 ppm. Product No. 8 contained 479 ppm nickel and 329 ppm chromium. Product No. 22 contained 1210 ppm nickel and 1170 chromium. Qualitative tests showed some of the chromium in the talcum products to be in the hexavalent state. The nickel, chromium, cobalt, and manganese in the talcum products may have come from the talc mineral deposit (10) or from the alloy metals of the pulverizing equipment used in reducing the talc (13). The zirconium content of the products were all under 10 milligrams per gram (mg/gm) except for products No. 9 and 17, which had 20 and 30 mg/gm respectively. The titanium, zinc, and iron ranged from a few tenths to 50 mg/gm of talcum and were probably present as pigments or opacifiers. The magnesium content of the products were all over 19 mg/gm, except for product No. 9 which had only 0.5 mg/gm. The magnesium was probably present as an additive \n the formulation or as a part of the talc molecule or other amphiboles in the products. The aluminum and silicas were in all probability associated either HER 0000751 \ -G- with the talc molecule, or additives such as koalin, or the base material from which the talc was derived. Known Health Effects of Talc Much of our knowledge of the health effects of talc is derived from studies of occupational exposures in its mining, milling, and industrial use. In extrapolating this knowledge to the cosmetic use of talcum powder, it must be recognized that the pattern of exposures in the use of talcum prod ucts varies markedly from person to person, not only in frequency of use but also in amount and in location. In contrast to industrial exposures where the pattern is likely to be more continuous with accompanying peaks, exposure in the use of cos metic talcum products is very intermittent with peak exposures dominating. The exposure pattern may continue a lifetime, especially if the use of talcum is established in the earlier years as a part of personal habits. The ^ c; - j i.c- ijjiQJCXoi i ircir I'.'.xv.s'.vrM ox*;; sure J " .Tcjthat have r_. *. - l^ere im_. ...y however, J " ~j w,^. ec;ic^a.irom-tiie-usa^.cosmetic .talcum products. 'j Mining. Milling, and Industrial Use U'l.- wIL'.ical entity nr rn1rLp'nPiirnjir--nmnsigf-l'talcosishas bfi^r- ') pbserved-repeatedly in^workers"vftnTong^exaosiirp m triTr in its mjnXng, ? -r.d industrial use J11^L5.16.171. Elongated, terminally clubbed pulmonary fibrous bodies, both segmented and unsegmented and similar in HER 0000752 -7 - morphology to ferruginous bodies, have been found in talc workers, but these workers had received a mixed exposure -- to talc, tremolite, >____________ anthophyllite, and silica (18,19). In_ " cc-... -v `o r .iXC.Cv wU.--.Q. 3 >::p.general pcpuiutio.t. Jin pulmonary cancer from asbestos, the role of fibers and trace metals is uncertain. Some investigators have assumed the fibers play a dominant and direct role; more recent investi gations indicate that the fibers may have been only an index concealing a spectrum of unidentified agents and relationships (13). Surgical and Cosmetic Use OortctT cuian-jous rer.ecio'.s from vi i ar^^rYvr..^'5rnms~'~and mese have~b3en rare ~(2jL, 22). Talcum powder, however, is no longer used on surgical gloves and should not be applied to broken skin. Occasionally, perfume oils used in talcum powder formulations sensitize the skin and produce dermatitis (23,24). Conclusions With the exception of 4 of the 22 cosmetic talcum products analyzed, the levels of free silica, cobalt, nickel, chromium, and manganese were generally of a low magnitude and within a narrow range. It is not known whether the four products represent a significant proportion of sales in the industry or to what extent the sources of the talc in these four formulations are the same as sources of talc specified for use in other talcum products HER 0000753 -8in the competitive market. The levels of silica, chromium, and nickel in these four products are sufficiently high, .however, to be of concern in their potential to cause disease. probably contained minor amounts of *"" `':v. . ..'.i 7 meaning of the presence of these ferruginous bodies, however, is uncertain. Industry has the know-how to safely handle fibrous material as well as toxic metals such as nickel, chromium, cobalt, and manganese once adequate criteria have been established. Unknown significant amounts of such materials in products that may be used without precautions may create an unsuspected problem. For this reason continued research and investi gations and communication of findings are necessary in this area. Acknowledgements The authors acknowledge, with appreciation, the technical assistance of Harrold B. Norris who made the free silica determinations; Patricia L. Maurer who made the atomic absorption spectrophotometric determinations for nickel, cobalt, chromium, and manganese; John R. Carlberg who made HER 0000754 -9the emission spectrographic determinations for zirconium, titanium, zinc, iron, magnesium, and aluminum; and Stephen Bayer and Ralph Zumwalde for the per cent fiber analysis. 1I- \ HER 0000755 - 10 References 1. Marchand, F.: Ubcr Eigcntumliche Pigmentkristallc in Den Lungen. Verh Dtsch Path. Ges. 10: 223 (1906). 2. Thomson, J. G., R. O. C. Kasciula, and R. R. MacDonald: Asbestosis as a Mfcrdern Urban Hazard. S. Afr.Med.J. 37: 77 (Jan. 1963). 3. Thomson, J.G., andW.M. Graves, Jr.: Asbestos as an Urban Air Contaminant. Arch, of Path. 81: 458 (May 1966). 4. Cauma, D., R.S. Totten, and P. Gross: Asbestos Bodies in Human Lungs at Autopsy. J. Amer. Med. Assoc. 192: 371 (May 1965). 5. Webster, L: Annual Report of the Pneumoconiosis Research Unit of the South African Council for Scientific and Industrial Research, Johannesburg, South Africa (1965). 6. Meurman, Lauri: Asbestos Bodies and Pleural Plaques in a Finnish Series of Autopsy Cases. Acta Path. Microbiol. Scand., Supplementum 181 (1966). 7. Anjilvel, L., andW.M. Thurlbeck: The Incidence of Asbestos Bodies in the Lungs at Random Necropsies in Montreal. Canad. Med. Assoc. J. 95: 1179 (Dec. 1965). 8. Cooper, W.C., and L Tabershaw: To be published. 9. Cralley, L.J., R.G. Keenan, J. R. Lynch, andW.S. Lainhart: Source and Identification of Respirable Fibers. Amer. Indus. Hyg. Assoc. J. 29: (Mar.-Apr. 1968). HER 0000756 -11 10. Deer, W.A., R.A. Howie, and J. Zassman: Rock-Forming Minerals. Vol. 3, Sheet Silicates, p. 126, John Wiley and Sons, Inc. 11. Kirk, R.E., D. F. Othmer: Encyclopedia of Chemical Technology. The Interscience Publishers, Inc. New York 13: 565 (1954). 12. Ibid. 6: 357 (1965). 13. Cralley, L.J., R.G. Keenan, and J.R. Lynch: Exposure to Metals in the Manufacture of Asbestos Textile Products. Amer. Indus. Hyg. Assoc. J..28: 452 (1967). 14. Hogue, W. L., Jr., and F.S. Mallette: A Study of Workers Exposed to Talc and Other Dusting Compounds in the Rubber Industry. J. Indus. Hyg. & Toxicol. SI: 359 (1949). 15. Messite, J., G. Reddin, and M. Kleinfeld: Pulmonary Talcosis, a Clinical and Environmental Study. AMA Arch. Indus. Health 20: 408 (1959). 16. Schepers, G. W. H., and T. M. Durkan: The Effects of Inhaled TalcMining Dust on the Human Lung. AMt A Arch. Indus. Health 12: 182 (1955). 17. Seder, A.O., J.S. Gryboski, andH.E. Macmahon: Talc Pneumoconiosis. AMA Arch. Indus. Health 19: 392 (1959). 18. Kleinfeld, M., C.P. Giel, J.F. Majeranowski, and J. Messite: Talc Pneumoconiosis: A Report of 6 Patients with Postmortem Findings. Arch. Environ. Health 7; 101 (1963). \ \ I HER 0000757 - 12 19. Kipling, M. D., and A. O. Bech: Talc Pneumoconiosis. Trans. Assoc. Indus. Med. Officers J10: 85 (1960). 20. Kleinfeld, M., J. Messite, M. Zaki, and O. Kooyman: Mortality Among Talc Miners and Millers in New York State. Arch. Environ. Health 14: 663 (1967). 21. Lichtman, A. L., J.R. McDonald, C.F. Dixon, and F, C. Mann: Talc Granuloma. Surg. Gynec. & Obst. 83: 531 (1946). 22. Tye, M. J., K. Hashimoto, and F. Fox: Talc Granulomas of the Skin. J. Amer. Med. Assn. 198: 1370 (1966). 23. Burks, J. W.: Dermatitis Due to Cosmetics. Southern Med. J. 55: 1006 (1963). 24. Spoor, H. J.: Skin Reactions to Cosmetics: Classifications and Diagnosis. New York J. Med. 60: 1940 (1960). I HER 0000758 Table I. Designated Analyses of Cosmetic Talcum Products Co ND ND 10 ND ND Microgram of metal per gram of sample. Milligram of element per gram of sample. J lO CD to to o o to CO o o o 03 GO O rH to rH O to rH 03 rH O O -3* o rH 3 A o rH CO A w * 2 rH to o o rH * .A cc A bO o &H o 03 o rH t- o 03 CO to rH o rH to rH 00 CM rH O to rH o rH O rH o rH 03 O 03 to rH o rH O rH rH o 03 bo s a3 z zN lO Q o === O' IA o to Q Z H os to 03 00 03 rH <s< CO 00 00 C0 03 to c- 00 CO CO oo oo o o o oo o o o oo o CM CO CM rH rH p CSJ H V oo 03 rH V Oo eo rH V 53c co H 03 03 00 C- ttoo o rH 03 rH rH to ** M* rH CO CO rH CO rH 05 rH o 03 03 03 00 rH co rH o IA CO 03 GO V s* aa. H 03 rH o H V o CM o C" CM H rH O rH 0rH o 'C o rH V 0* CM o 03 orH o rH V o rH V CrHO CD rH 05 rH Tf rH rH 03 05 CM c> rH O rH 03 rH zh o 0) o rH O rH Tf rH rH o rH 05 03 Q CM rH CM 03 03 rH o rH oiH o rH rH rH o rH 05 o rH rH 05 o 0- V V 03 V V CO V V VV VV rH rH azeo o rH o rH c- CO o rH rH Q 03 g o rH iH to 03 GO rH o H o o rH o CO o CM O rH rH rH rH rH rH 03 rH rH VV V VV V VV V V oo 03 CM 03 CO to rH CO 05 Tt* CO 6- CO 05 CM c- C* o CM co to eg 0) (4 Ph 03 o o o CM o rH CM CO C0 o rH to rH rH rH rH rH rH O rH rH CO o a H 05 rH rH 03 eo CM 05 rH o M 00 rH rH 05 rH rH CM 00 00 to 03 CO CM 00 CM GO CM 03 rH 03 rH CO rH 00 rH CO rH to CM rH o sz s 4* o o rH CM eo 73 H *D o IA C0 c 00 05 rH rH rH CM rH CO rH rH IA rH CO rH e- rH 00 rH 05 rH CM rH CM CM 03 / HER 0000759