Document jBbXBV0OG8ENQ98w0Ryx2jGZ

Asbestos Information Association/North America jeexE&ooraoaxsKaeoc 1660 l street, n. w. jNeMCXHCSXJWOMfXWRTGl Washington, D. C. 20036 PLAINTIFF'S EXHIBIT October 1, 1973 MEMORANDUM TO MEMBERS SUBJECT: FDA Proposed Rulemaking "Asbestos Particles in Food and Drugs" Attached is the announcement of the Food and Drug Administration notice of proposed rulemaking on "Asbestos Particles in Food and, Drugs as appeared in the Federal Register, Vol. 38, No. 188, Friday, September 28, 1973. The Association proposes to comment on this matter and encourages comments by individual members as well. Deadline of the FDA for receiving comments is December 27. 1973. It is requested that information to assist in tne preparation of the Association response be received by November 5. R. H. Mereness Executive Director Attachment UCC 003491 A , o ^> n received OCT 3 1973 WM C. THS53EH 27076 PROPOSED RULES DEPARTMENT OF HEALTH. EDUCATION, AND WELFARE Food and Drug^dministration [ 21 CFR Parts 121,128,133 ] ASBESTOS PARTICLES IN FOOD AND DRUGS Notice of Proposed Rulemaking The Commissioner of Food and Drugs has received a petition from the Center for Science to the Public Interest, 1779 Church Street NW,, Washington, D.C. 20036, and the Environmental Defense Fund, 1525 18th Street NTV.. Washing ton, D.C. 20036. requesting promulgation of regulations under the Federal Food, Drug, and Cosmetic Act to prohibit the adulteration of food and drugs with as bestos. Petitioners request that the Com missioner publish in the Federal Regis ter "immediately (within 30 days)" the following proposed regulations: t. Subpart P ot Part 121 Is ameoded by adding tha following section: $121.___ Fillers containing asbestos. "poods that have come Into contact with filters made wholly or partially of asbestos may reasonably be expected to become cca'laminated with asbestos panicles wench may ` by injurious to health when Ingested. Ac cordingly, any food or food additive produced, manufactured, processed or prepared using a filter made wholly or partially of asbestos aboil be deemed to be adulterated la violation of section 407(a) of the Act. 3. Part 133 is amended by adding the fol lowing sections: f\ i ij 3 U J 133.___ Filters containing a-licslns. Drugs posted tluouch filters made wholly or partially of asbestos may reasonably he expected lo breome corumnlnaied with asbestos purtlclc- which may oe Injurious to health when Injected or Invested. Accord ingly. any drop or drug comjxincnt produced, manufactured, processed or prepared using a filler made wholly or partially of asbestos shall be deemed to be adulterated In viola tion of section 401(a) of tbo Act. $ 133.___ Tele containing asbestos. Tate Is a naturally occurring hydrous magnesium silicate which may reasonably be expected to be contaminated with asbestos particles. Asbestos particles may be Injurious to health when Ingested or Injected. Accordlngly. It Is not considered good manufactur ing practice to add talc, directly or Indirectly, *4 a component In the production, manu facture, processing or preparation of any drug, unless the manufacturer or processor of the drug first demonstrates by appropriate tests tb&t the talc so used Is fret of asbestos ponlcjes. Any drug or drug com ponent containing tale which has not'been demonstrated to be free of asbestos particles shsll be deemed to be sdulteratcd In riotstlon of section 01 (a) of tbs Act. Petitioners also request that the Com missioner "immediately (within 30 days from the receipt of this petition)" promulgate as a final regulation a zero tolerance for asbestos particles in tale intended for use as a food additive, pur suant to the proposal published in the Federal Register of August 12. 1972 (37 FR 16407), and take whatever other ac tion the Commissioner deems necessary to eliminate contamination of food and drugs with asbestos. A complete copy of the petition and its attachments may be reviewed at the office of the Hearing.Clerk, Food and Drug Ad ministration. Rm. 6-86. 5600 Fishers Lane, Rockville. MD 20852, during work ing hours, Monday through Friday, The Commissioner has carefully re viewed the petition, its attachments, and other available information, and has reached the following conclusions. Each conclusion indicates the source reference upon which the conclusion is based and copies of all referenced material are available from the office of the Hearing Cleric. "Asbestos" is a generic term for a num ber of hydrated silicates that, when crushed or processed, separate into flexi ble fibers made up of fibrils. Although there are many asbestos minerals, only (lx are of commercial importance. Chrysotile, a tubular serpentine mineral, accounts for 95 percent of the world's production. The others, all amphiboles (crystals with 3 groups of metal ions), are amositc. crocidolite. anthophyiute. tremolite and actfnollte. These asbestos minerals differ in their metallic ele mental content, range of fiber diameters, flexibility, harshness, tensile strength, surface properties, and other attributes that determine their industrial uses and which may affect their rcsplrabillty. dep osition. retention, translocation and biologic reactivity (Ref. I). Many products such as cement, floor ing, shingles, pipes, filters, textiles, etc, contain asbestos of one kind or another. FEDERAL REGISTER, VOt. 3(, NO. ill--FRIDAV, SEPTEMBER 28, .1V7J UCC 003492 PROPOSED RULES 27077 There ere great variations among such products with respect to the chances of fiber release during the use of the prod uct. Tlie likelihood of such liber release depends predominantly on the ease with which the fibers can be dislodged and on the degree to which the vise of the prod uct destroys the fibers. Almost all as bestos fiber used In the United States for manufacturing products becomes tightly bound within the products and usually undergoes little actual abrasion or wear before being discarded. Asbestos cement products (accounting for most of the asbestos used in the United States), shingles and floor tiles are in this cate gory. Some asbestos-containing products, mesothelioma, occur at rates greater than in persons not so occupationally exposed, 'mere is a 5 to 7 fold increase In lung cancer In asbestos workers which is noted as early as 10 to 14 years after onset of exposure and Ls significant at 20 years (Rets. 9 through 15). Seven per cent of deaths in asbestos workers arc caused by pleural and peritoneal meso thelioma (Kefs. 1C through 33). This Is a marked increase since this tumor is ex tremely rare in the general population. There is suggestive evidence concerning an Increase m ute'ratc of gastromtesti- na) malignancies in asbestos workers (Ref. 34). There Is considerable evidence that were totally cleared by the gastrointes tinal tract In 48 hours and no asbestos was delected In the animal tissues at the end of 1 week. The gastroinstcstinal tract of the rat seemed to provide an clfective barrier to iienetration. In a published study by W. E. Smith, ef af. (Ref .41), hamsters maintained on a diet of 1 percent chrysotile or amositc through life had no gastrointestinal tumors. A report by Westlake, Spjut and Smith (Ref. 42) indicates that the rat colonic mucosa is penetrated by chryso tile after feeding a diet containing 5 per cent asbestos for 3 months. Cunningham and Pontefract (Ref. 43 such as brake linings, are subjected to great friction; their rate of wear is con siderable. and at times they are almost completely worn away. In the case of brake linings, the application of force is so Intense and the heat created so great that most chrysotile fibers are destroyed mast human lungs harbor thousands or millions of asbestos fibers although most people do not have asbestosis iRefs. 35 through 37). This is due to the ubiquity of the substance. Some of these fibers are chrysotile asbestos, and ampliiboles are probably present also. This number of and 44) injected chrysotile fibers (9.4 and 94 x 10') directly into stomachs of rats. Fibers were found in blood and other organs, 2-4 days after treatment. Control rats, although having no asbes tos in blood, also had high levels of asbestos in tissues. by being converted into another sub fibers is relatively small in most persons These workers found that, wherpas the stance which is non-flbrous. Neverthe not occupationally exposed to asbestos tap water in Ottawa (having a filter less, an appreciable percentage <1 to 3 compared with the numbers found in the plant) contained about 2 million fibers percent) remains as fibrous asbestos, occupationally exposed. The systematic per liter, the quality of fibers In soft and fiber release from products such as application of quantitative techniques, drinks and alcoholic beverages purchased asbestos, cloth, paper and sprayed fire measuring both coated and uncoatcd In the Ottawa area ranged from I to 12 proofing materials Is a serious source of fibers, is needed to define a gradient of million fibers per liter. Even with the emission. This usually occurs in densely accumulated fibers for correction with technical problems of methodology, this populated areas. Most of the pipes de incidence of disease, on the one hand, seems to indicate that in some beverages livering drinking water are of a mixture and history of environmental exposure, the asbestos content may be about the of cement and asbestos. on the other. same as in water, whereas, in others, it Solid wastes produced during manu The methodology for quantification of may be increased. Thus, it is reasonable facture of asbestos-containing products, asbestos fibers of varying sizes is such to conclude that water and many other use of such products, and demolition that the results obtained in one labora beverages for human consumption con con be emission sources. These waste ma tory may vary substantially from those tain substantial amounts of asbestos terials are usually disposed of without in another. An inter-agency govern fibers. regard to their potential as emission mental task force together with other There is some evidence that asbestos sources. Alternate methods of disposal scientists working in this field is cur filters may remove some asbestos mate often result in commingling of asbestos- rently attempting to develop standard rial. In a preliminary experiment per containing wastes with municipal wastes technology which can be applied to the formed by the Food and Drug Adminis In open dumps and thus create a long identification and qualification of asbes tration. asbestos was added to distilled term emission source. tos fibers. The Environmental Protection water and dispersed evenly by the action Asbestos fibers thus are ubiquitous In Agency is currently investigating four of an ultrasonic generator. Electron air, water and a targe percentage of the separate techniques in order to establish microscopy of this material clearly earth's crust. The amount of this ma the best method for identification, quan showed largo numbers of asbestos fibers. terial which additionally is added to the tification, sizing and typing of asbestos This material was then filtered through environment and to food and drugs by particles and fibers. At present, the Na an asbestos filter, and electron micro the use of asbestos filters is not known. tional Institute for Occupational Safety scopic examination of the filtered mate Therefore it is obyinne that, the presence and Health (NIOSH) recommends, as a rial showed a reduction in the number of or asoestos in these products is only one technique for sampling of air, a method asbestos fibers. small sum ce_oLfvpqsnrg: ' ' ASDestoslnhalation has been known to be an occupational hazard in workers in asbestos mines. The asbestos is inhaled and lodges in the lungs causing the de velopment of a fi biotic disease known as "asbestosis." Asbcstosis. or abcstotic pneumonoconiosis, was the first clearly demonstrated adverse clfcct of asbestos In man. It is characterized by a pattern of rocntgcnographic changes in the lung consistent with diffuse interstitial fi brosis of variable degree and at times with fibrosis and calcification of the pleura;.clinical changes that include line rales, finger clubbing and shortness of breath, each of which may be absent in on Individual ease: and physiologic based on counting fibers greater than 5 microns in length using phase contrast illumination at 430x magnification with a 4 millimeter objective (Refs, 38 and 39), This technique is currently recom mended for liquid materials until more accurate and sensitive practical methods are developed. However, as indicated be low, another method ls proposed for analysis of asbestos fibers in a material sucli as talc. The evidence concerning the possible hazard from ingestion of asbestos par ticles Is contradictory and inconclusive: In an unpublished study by L. M. Swinbuni tllef. 40), asbestos particles were fed once a week to SPP Wistar rats for lfi and 18 weeks. The material was Nicholson and his colleagues (Ref. 45) Investigated a number of samples of par enteral drugs and found asbestos fibers. Based on their report a study was under taken by the Food and Drug Administra tion concerning contamination of par enteral drugs with asbestos. Although the data are still preliminary, the following observations are pertinent. Parenteral drug samples were collected from a num ber of firms. Based on phase contrast microscopy. 11 of 13 Samples had clcarcut evidence of the presence of asbestos, one sample was questionably positive, and one was negative. The number of fibers ranged from 2 to 27 in the positive specimens of variable sample size. Using electron microscopy. 12 of the 12 samples chnngcs consistent with a restrictive lung ndministcrcdln butler. Although the par examined were jiosiUve. Quantitation is disorder (Refs. 2 through 8). ticles were of the size range known to not yet complete. In these workers In asbestos mines, produce tumors by oilier modes of ad In this survey, seven of 13 manufac malignancies of Utc lung and of Uie body ministration. no ttunoigenic effect was turers of parenteral drugs do not urc as lining tissues, namely lung cancer and noted. With a single large dose, the fibers bestos filters; four Anns use such idlers K0EAt MGISrtK, VOU Jt, NO, III--FttOAT, SEPIEMBM 21, W3 .fa ' f J d 7 UCC 003493 'v 27078 PROPOSED RULES ' folfo-A-cd. by final mi'tnbrnno tyre filters tone of these uses ;usl>o:;l(v fillers for ILs rfn.se water without final flltnillon of such water!: and two firms u:.n .-v;he:;U filters only for their rinse water, williout final filtration. The prcliininary reiiort of these studies Is on display at the OiHrc of the Hearing Cleric. Any other scientific data In this recard should be submitted to the Hear ing Clerk. Certain parenteral drugs, such as blood fractionation products, may be filtered several times Uirourrh asbestos filters. Thus far. it is not Unown with certainly wiietlier tlic moi-c viscous products could be successfully processed through ter minal membrane filters without com promising safety, identity, strength. . quality or purity. The precise eifect of asbestos pad duration on removal of pyrogens (Ref. 46 and 471 is not com pletely known at the present time. Currently the Pood and Drug Adminis tration Is surveying the industry for Information concerning the use of asb estos filters. Results of this survey will be incorporated in the public record. Although the major experimental studies of asbestos have involved inhala tion of fibers so as to simulate occupa tional exposure, several studies have been performed to investigate the eifect of parenteral inoculation of asbestos fibers. In 1938, Schmiihl (Ref. 48) reported that implantation of asbestos fibers and crumbs in cither the subcutaneous tissue or In the peritoneum lead to the develop ment of malignant tumors (sarcomas) in 11 of 30 rats which survived longer than' 15 months after such Implantation. Roe and his colleagues (Ref. 49, 50, 51) have performed a number of studies in which asbestos fibers were injected sub cutaneously (Ref. 49) into the flanks of mice. In the first experiments, crocidollte, omositc and chrysotiic asbestos fi bers were used and each animal was in jected twice subcutaneously in both flanks with 10 milligrams of fibers in saline with an Interval of five weeks be tween the injections. Seven of seventyone mice which survived 40 weeks or more developed Injection site tumors, fn addition, one mouse developed a meso thelioma of the peritoneum underlying the injection site. The injection site sarcomas were produced by ail three types of fibers. In addition. Roe ct cl (Ref. 49) showed that the asbestos fibers were w-idciy disseminated from the local Injection sites being deposited rather selectively on the serosal surfaces of the abdominal organs and the retroperi toneal structures as'well as on the peri cardium. diaphragm, pleura and adja cent parts of the lungs and heart. These serosal surfaces reacted vigorously to the presence of the asbestos fibers and in 10 of 71 mice, malignant mesotheliomas of the thorax and/or abdomen developed. In a later study (Ref. 51) Kanazawa ef of showed that, after subcutaneous , Injection of asbestos fibers in mice, libers could be found to have disseminated to regional and distant lymph nodes, spleen. kidneys and occ.xdonally to brain tissue suggesting that some asbestos may enter the circulation. Thus, there Is experimental evidence (hat parenteral administration of asbes tos fibers may lead to wide dissemination Of such fibers In animals and to the de velopment of local malignant tumors as well as malignant mesotheliomas of the pleura and peritoneum similar to those that occur after inhalation of asbestos fibers. The problem of asbestos in the total environment, to which the worldwide scientific community is addressing itself, is very complex. The Environmental Pro tection Agency has published in the Fedkhm. RscistE* of April 6, 1973 (38 FR 8830) national emission standards for asbestos milling and manufacturing based on the determination that asbestos is a hazardous air pollutant. This stand ard has been developed despite the fact the EPA also recognizes that a `'stand ardized reference method has not been developed to quantitatively determine the content of asbestos in a material." The present status of this problem is summarized by the report of a committee prepared subsequent to a meeting spon sored by the International Agency for Research on Cancer (Ref. 52). The Food and Drug Administration's review of this report indicates the following areas of further research are necessary: (1) Further epidemiology, particularly with respect to past exposure to asbestos and cancer of sites other than lung, pleura, and peritoneum. (a) Assessment of excess cancer risks following exposure to only one type of fiber. (b) Investigation of whether reduc tion of asbestos exposure in lungs below those causing asbestosis abolishes excess risk of carcinomx (c) Investigation of evidence of an in creased risk of cancer resulting from as bestos in water, beverages, food, or liquids used for tho administration of drugs. (2) Development of methods of quan titative assessment, size analysis and characterization of particles and fibers. Smusca 1. "Asbestos, the need and feasibility of air pollution controls," Report of the Committee on Biologic Effects of Atmospheric Pollutants. National Academy of Sciences, 1971, 3. Cooke, tV. E: "Fibrosis ot the bungs due to the Inhalation of Asbestos Dust," Bnt, A/rd. 7,, 2:147. 1024. 3. Cooke. W. E.. "Pulmonary Asbestosls," Brit. A/rd. 7,, 2:1024-1025, 1027. 4. Drcessen, W. c.. J. M. Dallavalle. T. L. Edwards, J. W. Miller, and R. Ii. Sayers. "A Study of Asbestos in the Asbestos Textile Industry." Public Iteafth unit., 241. Washing ton. U h. Government mating OUicc, 1938. 126 pp. 5. McDonald. S. "History of Pulmonary Asbestos is." Bnt. AW. j,, 2:1025-1026. 1927. 6. Mercwcther. E. re. A.. "The Occurrence of Pubnniiitry Fibres Ls and Other Pulmonary Affections In Asbestos Workers." 7. fnrt. Nyy, 72:100-223 and 72:239-257. 1030. 7. Mills, it. O., "Pulmonary Asbestosls: Re port of a ciuc," Minn. Med., 73:41)5-199, 1B30. 8. Soper, W. B, "Pulmonary Asbestoses: A report of a ea.se and a review," Am. Rrv. Tuberc, 22:571-504. 1930. 0. Lynch. K. M, and W. A. Smith, "Pul monary Ailbrstosls III: Carcinoma of lung In nsbeslo-slIlcosB." Am. 7. Cancer, 24:50-04. 1935. 10. Doll. R.. "Mortality from Lung Cancer in Asbestos Workers." Bril. J. tndustr. A/rd.. 12:81-80. 1055. 1). Buchanan, W. D, "Asbestosls and Primary Intrathoraelc Neoplasms." Ann. N. Y. Acad. Set., 732:507-518. 19G5. 12. Cordova, J. F,, if. Tcsluk and re. P. Kmidtson. "Asbestosls and Carcinomas ot the Lung," Cancer, 15:1181-1107. 19C2. 13. Gross. P,, R. T. P. dcTrcvlile. E. B. Tokcr. M. Kaschak and M. A. Babyak. "Experimental Asbestosls. The development of lung cancer in rats with pulmonary deposits of chrysotue asbestos dust." Arch. Envtrtm. Health, 75:343-355, 1967. 14. SeHkoff. I. J., J. Churg and E. C. Ham mond, "Asbestos Exposure and Neoplasia," JAMA, 166: 23-26, 1904. 15. Borow, M.. A. Conston. L. L. Llvorneie ar.d N. Schalet, "Mesothelioma and Its Asso ciation with Asbestos," JAMA, 201:587-591, 1967. Id. Elmes, P. C,, W. T. E. McCaughey and O. L. Wade. "Diffuse Mesothelioma of the Pleura and Asbestos," Brit. Med. 7, 7:350353, 1965. 17. Elmes. P. C. and O. L. Wade. "Relation ship Between Exposure to Asbestos and Pleura Malignancy la Belfast," Ann. N.Y. Acad. Sci.. 732:540-557, 1965. IS. Enticknap, J. B. and W. N. Smlther. "Peritoneal Tumor in Asbestosls." Brit. J. lnd. Med, 27:20-31. 1964. 19. Fowler, P. B. S., J. C. Sloper and E. C. Warner. "Exposure to Asbestos and Meso thelioma of the Pleura." Bril. .Wed. J., 2:211- 313. 1964. 20. Hammond-. C,, I. J. Selikoff and J. Churg. "Neoplasia Among Insulation Workers In tho United Slates with Special Reference to Intraabdominal Neoplasia," Ann. N.Y. Acad, kef, lit:519-525. 19G5. 21. Hourihane. D. O'B, "The Pathology of Mesothelioma and an Analysts of Their As sociation with Asbestos Exposure," Thorax. 79:260-278. 1964. 22. Lichen. J. and H. Plstawka. "Meso thelioma and Asbestos Exposure." Arch. Environ. Health. 74:559-583, 1967. 23. Mann. R. H_ J. L. Orosh and W. 11. O'Donnell. "Mesothelioma Associated with Asbestosls," Cancer, 79:531-528, 1968. 2*. McCaughey. W. T. E, O. L. Wade and P. C. Elmes, "Exposure to Asbestos Dust and Diffuse Pleural Mesotheliomas," Brit: Med. 7., 2:1397, 1962. 25. McDonald. A. D,, A. Harper. O. A. Elattar and 7. C. McDonald. "Epidemiology of Primary Malignant Mesotheltxl Tumors In Canada.'* Cancer, 26:914-919. 1970. 26. Newhouse. M. L. and II. Thompson, "Epidemiology of hiceolhellnl Tumors In the London Area." N.Y. Acad. Sci., 132:579-5B8. 1965. 27. Owen, W, Q, "Mcsotbellal Tumors and Exposure to Asbestos Dust," Ann. N.Y. Acad. Sci, 132:G74-679, 1905. 28. Selikoff. L. 7, 7. Churg and E. C. Ham mond, "RclaLlon Between Exposure io As bestos and Mesothelioma," New Eng. J. .`.fed, 272:560-565. 1965. 29. Wright, o. W, "Asbestos and Health In 1969," Am. Ecu. flesp. Pis., 790:407-479, 19G9. 30. Selikoff. L. J, E. C. Hammond and 7. Chum "Asbestos 7:x|K>src. .Smoking, and Neoplasia," JAMA. 204:106-112. 1908. 31. Wncner. 7. C,, C. A. Sleggs and P. Marchand, "Diffuse Pleural Mesothelioma and Asbestos Exposure In the North Western Capo * rtBESAt KEG1SIE9, VOl. 39. NO. 188--f*lt>A7, SEPTEMBER 28, t?73 * A i k1 o UCC 003494 W'.'iy.'.i eji u i ir 'ir.',m-ei e i i.p ' .....pxcev*"*;' i mw H *8'i,r evmi'.W'1 ' mine .e . ni'Wf 's^'r- wmyv.iPM.vuaM levva-uMP ynw;i,"neywnvM PROPOSED RULES 27U7i) Province," Rrtt. /. hid. Jfcd, 17:2CO-27!, | MO. 22. Champion. P., "Two Cast* of Mal1/> pant McsoMtcitncm after Fxpoauro to An- brstoa/* Am. liev. llcsp. Dii+ 1971. 33. Lellkoff. L. J. and F.. C. Hammond. "En vironmental Epidemiology. lit. coimmimiy tifcds of Non occupational Environmental Asbestos Exposure/' Am. /. Pub. Health, 58: IGSB-ICCG. 1000. 24. W&cner, J. C.. "Epidemiology of Diffuse Mcsothclfal Tumors: Evidence of un Asso ciation from Studios In South Africa and the United Kingdom," Ann. ff.Y. Acad. Sci., *32:575-578, 19G5. 35. Churc. J.. E. C. Hammond. A. M. Laoges. VV. J. Nicholson. L. J. SclikofT and Y. Suaukt. "Biological Effects of Asbestos." presented at the National Institutes of Health. Feb. 1, 1973. 30. Aavllvel. L. and W. M, 'niu.rlbcclr, "Tlie Incidence of Asbestos Bodies in the Luncs at Random Necrospaics in Montreal/' Con. Med. Astoc.J.. 35:1173-1182. 19C6. 37. Cauna, D,, R. 3. Totten and P. Gross, "Asbestos Bodies tn Human Lungs at Au topsy/' JAMA. 192: 371-373. 1965. 38. "Criteria for a Recommended Stand ard--Occupational Exposure to Asbestos/' Report of Review Committee, National fn- etltttte for Occupational Safety and Health. Publication NO. HSM 72-10107 (1972). 30. Lynch, J. R. and H. E. Ayer, "Measure ment of Asbestos Exposure." J. Occup. Med-, 10: 21-24.1968. 40. Swinburne, L. M.. "The Ingestion of as bestos by rats (unpublished data)," personal communication to Bureau of Foods. FDA. 41. Smith, W. E.. L. Miller. R. E. Elsasser and V. D. Hubert, "Tests for Carcinogenicity of Asbestos/* Ann. tf.Y. Acad. Sci^ 232-ASG-A88, 1965. 42. Westlake. G. E.. H. J. Spjut and M. N. Smith, "Penetration of Colonic Mucosa by Asbestos Particles. An Electron Microscopic Study in Rats Fed Asbestos Dust," Lob. in- c*f.# 24:2029-2033, I9G5. 43. Cunningham. H. M. and R. Pontefract: (a) **Asbest05 Fibers In Beverages and Drinking Water," Mature. 232:332-333. 1971. (b) "Symposium on Industrial Chemicals as Food Contaminants." Journal of (he AOAC. 56:976-981. 1973. 44. Pontefract. R. and TI. M. Cunningham: "Penetration of Asbestos through the Diges tive Tract of Rats/' nature. 24J:352-353, 1073. 46. Nicholson, W. J.. C. J. Migglarc and L J. Sellkoff, "Asbestos Contamination of Parenteral Drugs, Science. 177:171-173, 3972. 46. Tul, C. and A. M. Wright, "The Pene tration of Non-Pyrccen Tn/usion and Other Intravenous Fluids by Absorptive Filtration/* Annofs Surg^ 116:412-125, 1942. 47. Remington's Pharmaceutical Sciences, "Parenteral Preparations, Pyrogens/' Chap ter 62, Utb Ed. (p^. 1524), 1970. 48. Schmaht, D., "Canecrogeue Wlrkung on Asbest be! Implantation von Ratten," Zeitschrift /ur Krebsforschung, 62:561-567, 1958. f 9. Harlngton, J. S. and P. J. C. Roe. "Stud ies of Carcinogenesis of Asbestos Fibers and their Natural Fibers." Annals of the N.Y. Academy of Sciences, 132:439-450, 1905. 60. Roe. F. J. C . R. L. Carter. M. A. Walters and J. S. llnrinpton, "The Pathoioplcul Ef fects of Subcutai.ccur. Injection* of Asbestos Fibers In Mice: Migration of Fibcis to SubmesotheUat Tissues and induction of Mvsothellomata/' inf. J. of Cancer, *023-038, 1007. 51, Kanazawa, K . M. 3. C. Blrbcck. R. L. Carter Mid F. J. C. Roe. "Migration of Asbes tos Fibres from Subcutaneous Injection Sites In Mice/* Dntish Journal of cancer, 24:90106.1970. 62. "Report of the Advisory Committee on AxbeKtrut Cancers to the Director of the In ternational Arency for Ke^utrft on Cancer,** Urxl.J. Irulustr. Med., 50:1110-180, 1973. brane filters. Is also requested. Finally, comment on methods of quantitative assessment, size analysis, and char acterization of particles and fibers, is The Commissioner recognizes th.it It is essential In order to develop final not possible to eliminate all sources of methods on which accurate and fair asbestos contact with food and drugs. compliance can be based. Asbestos Is used In virtually all pipes Therefore, pursuant to provisions of carrying drinking water, in buildings In the Federal Food, Ding, and Cosmciic which food and drugs arc manufactured, Act (secs. 402. 502. 701, 52 Stat. 1046- and in many filtering systems used in the 1047, as amended, 1050-1051, ns amended. manufacture of food and drugs, and Is 1055-1056, as amended; 21 U.S.C. 342. found ift some substances, notably water 352, 371) and under authority delegated and talc, used in the manufacture and to him (21 CFR 2.120). the Commissioner processing of'food and drugs. Ncvcrthe- of Food and Drugs proposes to amend less, the Commissioner also recognizes Title 21 of the Code of Federal Regula that asbestos fibers perform no functional tions as follows; purpose in talc and are on unnecessary 1. In Part 121 by amending 3 121.101 contaminant. It is therefore reasonable (d)(8) by alphabetically adding to the to require precautions to be taken in the table a new Item and in paragraphs (h> manulncure of food and drugs, as part of good manufacturing practices, to assure that the amount of asbestos fibers in any food or drug is reduced to the minimum feasible level. Accordingly, the Commis sioner has concluded to take the follow and (1) by revising the aitry for "talc", to read as follows; 121.101 Substances dial are generally recognized a* safe. * ing action: Cd) * * 1. In view of the demonstrated hazard in animals from injection of asbestos fibers, the Commissioner is proposing that Traded Toianac* Limitations ot nsuteihns the good manufacturing practice (GMP) regulations for drugs be amended to re quire that filtration procedures for pa rental drugs shall utilize either a non- <&) Mteralla&teos and or rtacrai nurposfl loed . asbestos-containing or non-fiber-releas additive*. ing filter such as a membrane filter or, if an asbestos-containing filter is neces sary, shall also utilize an additional nonasbestos-containing or non-fiber-releas Tnlc iitt# oTnsttt-stos fibers as determinM in ing filter such as a membrane filter to reduce asbestos fiber content to the min imum level feasible unless such a subse * Id chrtrlnr pm base and as an aaiJstKkicx aytnt !n forms uv:ti m molding food hapta. quent filter will compromise the safety, identity, strength, quality or purity of (h) * * the product. Tale (fre* of asbestos fibers as determined 2. The Commissioner intends to pro In I 121.2006). mulgate a final regulation for talc under } 121.200G as soon as a method for deter mining asbestos fibers in food-grade talc Is validated. Such a method is proposed below, os part of a repubiication of the earlier proposal In which no methodology 4 (1) * * * * Talc (free of asbestos fibers as determined In | 1212006). . was specified. The Commissioner con cludes that a final regulation for talc under Part 121 cannot be promulgated until a reproducible and accurate method 2. In Part 121 by amending Subpart E by adding the following new section: 121.2006 Talc. can be specified for compliance purposes. (a) Talc Is a naturally occurring 3. The Commissioner is also proposing hydrous magnesium silicate subject to that any talc used in the manufacture or a prior sanction for use in coating pol processing of drugs meet the specifica ished rice. It is found in natural deposits tions for this substance that will be im that may be contaminated with asbestos posed by i 121.2C06. fibers. - -- - 4. The Commissioner realizes that the (b) Good manufacturing practice re Issues raised in tins notice are complex quires that talc be free from asbestos ami have widespread ramifications. Com-/ ment is requested on all aspects of the fibers to the maximum extent prac public health significance of ingestiqh ticable. Accordingly, any food or food- and injection of asbestos fibers. Sinie packaging material containing talcTiiat adoption of any new filtration require ments may require use of additional equipment, comment on the availability oi appropriate equipment, the need for use of nsbestos-coiitainin;: filters as con trasted with filters which contain no isTlOl Ircc Ifflfh asbestos fibers as deter- mined by the method set out in para graph (c> shall be deemed to be adul terated in violation of section 402(a) (1) of the act. ..______ asbestos, and the lime needed to ob- ~'-- (c> The following method shall be tain and becin using non-asbestos- used to determine compliance with this contnlnlng final filters such os mem section: No. 189--Pt. I- ffOESAt UCISTte, VOL 36, NO. ll--fRIOAr, SEPfEMBfl 26, 1971 ^ ^JUJ UCC 003495 il a I'M'J1 : t I 1 ' P PH* n rrrr 27080 PROPOSED RULES (1) The various kinds of asbestos arc distinguished from talc mid from each other by their refractive indices, other optical crystallographic properties, and morphology as determined with a polar izing microscope (Methods of the Asso ciation of Official Analytical Chemists, 11th Ed., 1970. Sections 3C.S41-36.543, p. 717-721).* Talc occurs mainly in the form of thin plates, which may appear fibrous when seen edgewise in micro scopic view. Beta and gamma indices of talc vary from about 1.575 to 1.530, beta being very close to gamma. All of the principal refractive indices of chrysotile are less than 1.500. Chrysotile asbestos is therefore distinguishable from fibrous looking talc particles in a ,1.574 refractive Index liquid and the other five amphibole types of fibrous asbestos from talc in a 1.530 refractive Index liquid. The table of optical crystal lographic properties for talc and the asbestos minerals in subparagraph (3) shows refractive indices which are usually encountered in these minerals, but occasional samples may have indices which are somewhat higher or lower. For practical measurement of optical prop erties shown in the table, particles iden tified by this method should be at least 5 /an or longer. C2) Weigh out 1 milligram of a repre sentative portion of talc on each of two microscope slides. Mix the talc with a needle to spread evenly over the suitable area on one slide with a drop of 1.574 refractive index liquid, and then the other with 1.500 liquid, and place on each a square or rectangular cover glass suffi ciently large so that the liquid will not run out from the edee (co. 18 mm. square) and will provide a uniform par ticle distribution. Fibers counted by this method should meet the following cri teria: (1) Length to width ratio of 3 or greater <il) length of 5 m or greater (111) width of 5 ;im or less. Count and record the number of asbestos fibers found in each 1 milligram as determined from a scan of both slides with a polariz ing microscope at a magnification of ap proximately 400 X. In the 1.574 refrac tive Index liquid, chrysotile fibers with Indices less than 1,5-74 In both extinction positions may be present: in the 1.590 refractive index liquid, the other five amphibole types of asbestos fibers with Indices exceeding 1.590 in both extinc tion positions may be present. Check the extinction and sign of elongation for tentative identification. For specific Identification of asbestos fibers, make ad ditional mounts in appropriate refractive Index liquids, and refer to the optical crystallographic data in the table. A count of nut more than 1000 amphibole types of asbestos libers and not more than 100 chrysotile asbestos fibers per milligram-slide constitutes the maximum 1 Copies may bo obtained from: Association of OUlclal Analytical Chemists F.O. Dol 540. ncnjainln Franklin Station Washington. DC 20044 limit for the presence of these asbestos libers in talc. Thcso limits assure a purity of laic at least 93.9 percent free of amphibole types of asbestos fibers and at least 99.99 percent free of chrysotile asbestos fibers. (3) Optical crystallographic charac teristics of asbestos minerals and talc: KxAtm-c* or nr.r>u<TiTX Ihum** (i) Oobftt&noa &A T Eittacitoo Elongation AcUcveLIU.............. AuxMlt...:......... .... .. Anlliopliyttite ... Chrysotil*., CroeldoUta.. Talc....... TrrmoUte. . ............... ... t.eit 1.630 1. Ml Inclined.................. ... PoaltUa. 1.019-1. 6SS 1.620-1.010 1.04-1. Ot `1.6*4. 1.6*0 1.679 . 1.701 . Il..6ftM . 1.023 . Paraltot............... Positive. 1.023 . L*90-1.674 L 006-1,664 1.610-1.0*7 1600 . 1.631 . i.ei* l.'6 1.610 L 010-1. CM 1.630-1-0W 1.640-1.647 L&2> 1.630 1.640 1.03 1.634 1.602 1.4 1.604 1.617 Parallel........................ Positive. 1.60} 1.613 1.622 1.099-1.669 t. MT-l. 6G7 ,, 1.63 *1.94 ; 1.643 . 1.34 -1.00 . 1.5S5 . 1.643 1.643 i&U . 1.640 1.630 1.657 . 1.640 LM TwT 1.667 L 600 S.MS s. COS 1.657 . t0. . Parallel. `loot' . xtg&dT*. 1.097 .... L 639-1. M3 , 1.700 1.703 L 073-1. W0 Parallel or 2* or 3*^... PositJvo. 1.639 1 6S9 1.659_______________ _____ . 1.639 1.689 1.609 _______________ ____ _ tin 1.689 I.AJtO _______ ______ ________ L640 na&rlv-n 1.075....................................... L6U 1.6S0 1.600 ....................................... v 1.644 1.692 1-692 ..... .............. .............. ... 1.604 UM--------- ---------------- ------- i.6a LS99 1.604 1.613 1.604 ....................................... 1.623 Inclined............. ... . PostUTa. 1.699 . 1.613 i.a____ _________________ 1.099-1.412 L613-1.63d 1.62S-L 637 ....................................... 1.600 Iv6l8 1.627 ..................... ....... 1.603 1.614 LC33....................................... 1603 1.60-1.023 1.6)6 tl ....................................... L 613-1.63* 1.&24-1&S....................................... LtM 1,612 l-KS......................... ......... 1.604 1.617 1.630 ................................... . L609 1.633 1.636 .................................... 1.609 1.623 1.030 ....................................... 1.613 1.621 L034 ....................................... Hl+n. 3. In Part 133 by adding the following new paragraph (i) to 133.6 to read as follows: 133.6 Components. <i) Talc is a naturally occurring hy drous magnesium silicate which may reasonably be expected to contain as bestos fibers which may be Injurious to health. Current methodology cannot as sure the absence of asbestos in talc. Accordingly, any drug, drug Ingredient, or drug packaging material*containing talc that fails to meet the specifications of paragraph (c) of $ 121.2006 of this chapter as determined by the method set out in that paragraph shall be deemed to be adulterated in violation of section 501(ai of the Act. 4. By adding the following new para graph (j) to 5 133.8 to read as follows: 133.8 Production and control proce dures. * * (J) Use of asbestos-containing filters: Filters used In the manufacture of a parenteral drug or parenteral drug In gredient shall not release fibers into such products. No asbestos-containing or fl ber-releaslng filter may be used in the manufacture of a parenteral drug or par enteral drug ingredient unless it is not possible to manufacture that drug or drug Ingredient without the use of such a filter. If use of such a filter is required, an additional non-asbestos-contain:::? or non-fiber-releasing filter such as a membrane filter shall subsequently be used to reduce the content of any asbes tos-form particles in the drug or drug in gredient. Evidence for reduction shall be based on the use of the metheds de scribed in "Criteria for a Recom mended Standard--Occupational Expo sure to Asbestos," Report of Review com mittee. National Institute for Occupa tional Ssiety and Health. Publication No. HSM 72-10267 (1972).' Use of an asbestos-containing filter without subsequent use of an additional non-asbcstos-con- tainlng membrane filter is permissible only upon submission of proof to the Food and Drug Administration that use of a non-asbestos-containing membrane * Copies mny bo obtained from: Superintendent of Documents UiS. Government Printing OiUce Washington, DC 20102 FEDERA! REGISTER, VOL. 30. NO. 110--FRI0AY, SEPTEMBER 20. 1972 I UCC 003496 filler will, or is likely to. compromise the safety or effectiveness of the drug. Interested persons may.'on or before December 27, 1973, file with the Hearing Clerk. Food and Drug Administration, Rjn. 6-96, 5600 Fishers Lane, Rockville, MD 20852, written comments <prefer ably In qinntupticate) regarding the pe tition and the Commissioner's proposal. Comments may bo accompanied by a memorandum or brief in support thereof. Hie petition, background information re ferred to in this proposal, and comments received may be seen in the above office during working hours, Monday through Friday. Dated September 24, 1973. A. M. Schmidt. Commissioner of Food and Drugs. ' {FRDoc.73-20711 Filed 9-27-73.8:43 junJ Social and Rehabilitation Service [45 CFR Part 221 ] FAMILIES, CHILDREN. AGED. BUND, OR DISABLED INDIVIDUALS Service Programs; Correction FR Doe. 73-19242. published at page 24872 in the issue dated Monday, Sep tember 10,1973, is corrected by changing: 1. The number "233" in item number two of the preamble, fifth line, to *,233%M* 2. The code designation "221.6(a)(3) (1)" in item number two o the preamble, seventh line, to "221.6(c) (3) (i)"; 3. The code designation "211.6(a)(3) Oil)" in item number three of the pre.amble, fourth line, to "221.6(c)(3) (til)"; 4. The code designation "211.6(a)(3) <vU) '' in item number four of the pream ble, fourth line, to "221.6(c) (3) (vii)"; 8. The code designation "211.7(b) '* in Item number five of the preamble, fourth .line, to "221.7(b)"; 6 The code designation "211.9(b) (3)" In item number seven of the preamble, sixth line, to "221.9(b) (3)''; 7. The code designation "221.6(a)(3)'' In the words of issuance, number three, first line; and in 221.6(a) (3) Itself, first line, to "221.6(c) (3)": 8. The number "8'' in 5 221.6(a)(4), (now corrected to 5 221.6(c) (4)), fourth line, to "6"; and 9. The word "secured" in 5 221.9(b) (5). fourth line, to "secure". Approved September 24, 1973. Thomas S. McFee. Deputy Assistant Secretary lor Management Planning and Technology. |rn DOC.73-2072S Filed 9-27-73:8:45 am) Ai C' .T' O J/ a | UCC 0.03497 September 20, Dr. 7. J. Sail Uhlon Carfaido Belgiua B.V. l&jy~ `Avenue TjatHBQ =-*---- Brussels 5, BSXfllQM Subjects Asbestos Fiber gaporters Caaaltteo Seer Stoat Please refer to your letter of September 13 to Hr. Dexter. Tour feeling of continuing to cooperate with tfce Asbestos Fiber toporter* Caaoitteo oecns to be about the wisest course to fallow short, as you say, of incurring cay otilgstioaa In eny ether area of aur aobastes activities. As Freak Dexter points out, it is entirely possible too seats problem will axlea elsewhere so that sturt vu leant hero aoy continue to bo useful in more ways than one. On itnrlavlcg the history and eonsspaadatics, tbs ixapresnian is eoiaed that vo have tgom quits a says tosarri meeting the objections to iwiAlias asbestos, and Z vonaer vtatbar our vast vlth pallets, paper rather than cloth bags, cardboard homes, etc. doesn't stand us in good steed. Zh brief vs suggest you cooperate with the Caralttec end keep us informed of devclopaento. Very truly yours. T.2Mfrangos/jvp cat Mr. P.D. Baxter - DTO cc; Mr. J.J, Setter - BIO cst Mr. M.?. Ballmer - DTD ec i m*. I.C. SAysrs * Inrnlao Associate Product Marketing tensger UCC 003498 CHEMICALS AND PLASTICS .'o(Nawj A.y,K> '.ecatiort Mr. T. F. Frangos 2<fth Floor ~opy to 270 PARK AVENUE. NEW YORK. NEW YORK 10017 0a>* September 20, 1967 Originating Oapt, Antwriflft Uttor datm Sufcj*cf Relative to the letters Tom Hall wrote to me dated 5 September and 13 September, I suggest we answer as follows: a. The matter of price in the 5 September letter was already answered by you although you may wish to expand upon it. b. We appreciate the efforts to establish a `68 plan and await the details with interest. c. We recognize the problems of selling Asbestos T in Europe and are looking at the possibility of making "T" in Europe. We have nothing specific on this yet and any plans will be thoroughly checked with the" European people before they are firmed up. d. In reference to the work with the Importers Committee, I would recommend that we continue to maintain an active contact with this group and work with them. Naturally, we will wish to avoid obligations on our part insofar as possible and also if we can capitalize on the fact that we ship pellets we .should do so. Under any conditions, close communications with what's going on here I regard as highly desirable since there is at least a possibility that this same type of situation will spring up elsewhere. FDD/lr F. D. Dexter A UCC 003499 ~> / UNION CARBIDE BELGIUM N.V. RECEIVED SEP 19 to/ T.F. FRANGOS vmiF. NiRsr. 1415 TJH/MLF Bruxelles s. 13 September, 1967 Mr. F. D. Dexter 45th floor Union Carbide Corporation 270 Park Avenue New York 10017 Dear Frank: ^6^ 1 am enclosing with this a <^py of a report made by Ian Sayers, our asbestos representative!!! the U. K., concerning a recent meeting he attended of the Asbestos Fiber Importers Committee. The details of the meeting are given in the report. I believe it is evident from the report that all asbestos producers are facing a very serious problem in the U. K. in getting their material handled on the docks. It appears that the situation is not going to get any better as the popular publications continue their series of exposes about the dangers of asbestos. My purpose in writing to you is to ask for your comments concerning the advisability of our continuing to work with this industrial committee. 1 am sure you are aware that we have always avoided any close connections with the conventional asbestos producers so that we could maintain a free hand in all of our production and marketing decisions. In this case, however, it appears that we may have something to gain in joining in a common fight against an emotional problem. I feel that we should continue to cooperate with this group as long as we can do so without incurring any obligations In any other area of our asbestos activities. Here I guess you will have to rely on us to keep out of any unwanted entangle* menta. I do not intend that either Ian or X proceed further until we have some comments back from you on this subject. If you are neutral then we will proceed to cooperate at "arms length". 1 will keep you fully advised. What.do you think? T. F. Frangos A ; G3^0 Best regards, I. C. N. J. Sayers Setter THOMAS J. HALL. SCHiUaeiSAM - ant N ERPCM a AVENUE wOUISE I4B - QAUKCLLCS TEL. 103) 0.4P.20 - TEutX : 31577 TELCOS*. UN1CAR0ID6 ANTWCfllN T--C. (93) 3S.BQ.90 - TtLEX S3'BO TC.<_CO. UNICARBIDE - BAU>CU9 HAHOELSDCOISTEA ANTSgMPEN I <9.33J UCC 003500 v5/>Ysres Report /ctfCtSLE. S^"/r>/9>eiy Potsoajs.- 7/ 'JnPoPtSPS. AJeaj dozaz f Ps9C7-osey Z6cu'97~'0*'-s 'piPf/sSBAJK tvOPrtr/v& tsJiru Spts-j- Oa//0aj^ j-q //r>tT- /9PP/9 op t9f/7rr>o+j $' To BEstGG o*J US/*SGf'/sr7'rtSX^r &P6S. Oa <z*zPS sn/3? u/PrJT P<j/rrt o/e Coaj rfl SMeot/1) taoAceo <Saoo To ecv^ sar- DOCaoGI<?S` frerp Coazs-c CHRYsor/te /)iS0 Mv% Prsj^lsmS *J/ flfsti&Ts sbttl/a/o btsKsrtG SPHfPsnBAfr; "0r So AnoS'T* opt cutocoov^. ^ >y D Pass Sce/n TO TM/fU/e gy /S^C/Rns/G TU /jRoS^sT) sp- u/,^c Go s*u/s9y. Q)ytr*S yysA/KS y~HE C>OC*i CPS >aJ TBA/ts Yt> Stop A-S-P. aPS&'jFSToS SM/P/tj^aJ'XS. Aa UCC 003501 C 1491 *> INTERNAL CORRESPONDENCE UNION CARBIDE CORPORATION To (Nam/ O/rfjjoo Icnltu Copy to Mr. J. L. Myers Mining & Metals Division P. 0. BOX 579 Niagara Falls, New York OrfglnottflBOopfc Atmnring Uttor dato Medical Department. y Mr. R. E, Byrne Dr. C. U. Dernehl Mr. J. W. Rawlings Dr. H. B. Rhodes Dear John: Sobft Toxicoloj^ ^ I Lrr.'r.:CAL'ORiA 'VTy ca For some time it has been rumored, if not officially stated, that asbestos would be on the first list of hazardous materials to be named by EPA. Actually the few materials named so far are only the beginning of the list, I believe there will be added lead, arsenic, selenium, chromates, manganese, some nickel compounds, chlorine, sulfur dioxide, phosphine, arsine, nitrogen dioxide and various organic compounds along with other materials that I have overlooked. As a matter of fact, if toxic response to small quantities is the criteria, then the list will be long indeed. Therefore, you can reasonably argue, I believe, that the need for control of exposure to asbestos is not greatly different from a similar need in relation to many materials that are common in our daily lives. We believe that adequate control is practically possible. Asbestos, of course, is a toxic material that must be carefully controlled to prevent over-exposure of people who handle it or live near areas where it i3 handled. This we must accept. However, we argue that it is a material of great merit in many applications and that the control required is not greatly different from that we would provide for many other materials. This will be particularly noted as the nation feels the full impact of the new Occupational Safety and Health Act that became effective April 29, 1971. I see nothing to be gained by questioning EPA on the toxicity of asbestos at this time. There has been too much publicity on it recently for their stand to be modified without strong evidence to the contrary. Actually, if we can get them and other official agencies to accept a belief that control in use and application is reasonably possible, we shall have accomplished a great deal. Very truly yours, PWM: dp Paul W. McDaniel Industrial Hygiene Engineer k0 UCfc'003502