Document wm4g5RKJzOjLGR5mdoqRnM3

27076 PROPOSED RULES the enforcement procedures otherwise ment, and a summary of steps being 133.__ Filters containing asbestos. provided, he shall inform the affected taken in the interim to protect em Drugs passed through filtors mado wholly employees and official in charge of the ployees from being injured by th e haz or partlaUy of asbestos may reasonably bo establishment of the danger and require ard. A copy of th e plan will, be sent to expected to become contaminated with immediate abatement, including with-drawal of employees from th e dangerous circumstances. 1960.26 Notices of hazards. - (a) Each agency will establish a pro the safety and health committee of the agency for appropriate comment. The head of each agency will inform the Sec retary of Labor at regular intervals to be determined by the Secretary as to the progress made in carrying out the abate asbestos particles which may bo injurious to health when injected or ingested. Accord ingly, any drug or drug component produced, manufactured, processed or prepared using a filter made whoUy or partially of asbestos shall be deemed to bo adulterated in viola tion of section 401(a) of the Act. cedure for issuing notices of hazards dis covered upon inspection. Notices will de ment plan. Any changes in the abate ment plan will require .the submission of . 133.---- Talc containing asbestos. scribe with particularity the' nature of a new plan in accordance with the pro Talc is a naturally occurring hydrous the hazard, including a reference to the. visions of this section. standard or other requirement involved. The notice will also fix a reasonable time for the abatement of the hazard. A Subpart E--Federal Agency Internal Evaluation copy of the notice will be sent to the 1960.28 Duties of Federal agencies. magnesium silicate which may reasonably bo expected to be contaminated with asbestos particles. Asbestos particles may bo injurious to health when ingested or injected. Accord ingly, it Is not considered good manufactur ing practice to add talc, directly or Indirectly, official in charge of the establishment. (b) If a notice of hazard is issued as a result of a request for inspection under 1960.24(a) or a notifiction of hazard under 1960.24(c), a copy of the notice of hazard will also be sent to the em ployee or representative of employees who made such request or notification. (c) Upon receipt of any notice of haz Each agency shall conduct an annual detailed internal evaluation of its. occu pational safety and health program. Basic guidelines for this evaluation will be is sued periodically by the Office of Federal Agency Safety Programs. These internal evaluations shall be utilized by each agency for the purposes set forth in the applicable statutes and Executive Order as a component in the production, manu facture, processing or preparation of any drug, unless th e manufacturer or processor of the drug first demonstrates by appropriate tests th a t th e talc so used is freo of asbestos particles. Any drug or drug com ponent containing talc which has n ot beon demonstrated to bo freo of asbestos particles shall be deemed to bo adulterated in viola tion of section 501 (a) of the Aot. ard, the official in charge of an estab lishment will immediately post, such no tice, or a copy thereof, unedited, a t or near each place a hazard referred to in the notice occurred, except as provided below. Where, because of the nature of the establishment operations; it is not practicable to post the notice at or near each place of hazard, such notice will be No. 11612, as described in 1960.1, and shall be maintained and made available by each agency for review by the Office of Federal Agency Safety Programs. Signed a t Washington, D.C., this 24th day of September 1973. J ohn H . S tender, Assistant Secretary of Labor. Petitioners also request th at 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 talc intended for use as a food additive, pur suant to the proposal published in tho F ederal R egister of August 12, .1972. (37 FR 16407), and. take whatever other ac posted, unedited, in a prominent place where it will be readily observable by all [FR Doc.73--20707 Filed 9-27-73;8:45 am] tion the Commissioner deems necessary to eliminate contamination of food and affected employees. For example, where establishment activities are physically dispersed, the notice may be posted at DEPARTMENT OF HEALTH, > EDUCATION, AND WELFARE drugs with asbestos. A complete copy of the petition and its attachments may be reviewed a t the offleo the location to which employees report each day. Where employees do not pri marily work at or report to a single lo Food and Drug Administration [ 2 1 CFR Parts 121,128,133 ] of the Hearing Clerk, Food and Drug Ad ministration, Rm. 6-86, 5600 Fishers Lane, Rockville, MD 20852, during work cation, the notice may be posted at the location from which the employees oper ASBESTOS PARTICLES IN FOOD AND DRUGS. ing hours, Monday through Friday. The Commissioner has carefully re ate to carry out their activities. The of ficial in charge of an establishment will Notice of Proposed Rulemaking^' viewed the petition, its attachments, and other available information, and has take steps to ensure th at the notice is not The Commissioner of Food and Drugs reached the following conclusions. Each altered, defaced, or covered by other has received a petition from the Center conclusion indicates the source reference material. . for Science in the Public Interest, 1779 upon which the conclusion is based and (d) Each notice of hazard, or a copy Church Street NW, Washington, D.C. copies of all referenced material are thereof, will remain posted until the haz 20036, and the Environmental Defense available from the office of the Hearing ard has been abated, or for 3 working Fund, 1525 18th Street NW., .Washing Clerk. days, whichever is later. ton, D.C. 20036, requesting promulgation "Asbestos" is a generic term for a num 1960.27 Correction, of hazards. (a) The procedures for correcting haz ards will include reinspection by the of fice of the designated safety and health of regulations under the Federal Food, Drug, and Cosmetic Act to prohibit the adulteration of food and drugs with as bestos. Petitioners request th at the Com 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 six are of commercial importance. official to determine whether the correc missioner publish in the F ederal R egis Chrysotile, a tubular serpentine mineral, tion was made. If upon reinspection the ter "immediately (within 30 days)'' the accounts for 95 percent of the world's correction was not made, the designated safety and.health official shall make this fact known to the head of the agency for appropriate action.- following proposed regulations: 1. Subpart F of Part 121 Is amended by adding the following section: production. The others, all amphiboles (crystals with 3 groups of metal ions), are amosite, crocidolite, anthophylllte, tremolite an d actinolite. These asbestos (b) If in the judgment of the desig 1 2 1 .___ Fillers containing asbestos. minerals differ in their metallic ele nated safety and health official abate "Foods th a t have come into contact with mental content, range of fiber diameters, ment of a safety or health hazard will filters made whoUy or partlaUy of asbestos flexibility, harshness, tensile strength, not be possible within 30 working days, may reasonably be expected to become con surface properties, and other attributes the official in charge of the establish ment will submit an abatement plan to the designated safety and health official with a copy thereof ta the head of the agency and to the Secretary of Labor. Such plan will contain an explanation of the circumstances of the delay in abate ment, a proposed timetable for the abate taminated with asbestos particles which, may be 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 shaU be deemed to be adulterated in violation of section 402 (a) of the Act. 2. Part 133 is amended by adding the fol lowing sections: th at determine their industrial uses and which may affect their respirability, dep osition, retention, translocation and biologic reactivity (Ref. 1). Many products such as cement, floor ing, shingles, pipes, filters, textiles, etc., contain asbestos of one kind or another. FEDERAI REGISTER, VOL. 38 , NO. 188-- FRIDAY, SEPTEMBER 28 , 1973 HeinOnline -- 38 Fed. Reg. 27076 1973 PROPOSED RULES <> 27077 There are great variations among such mesothelioma, occur at rates greater were totally cleared by the gastrointes products with respect to the chances of than in persons not so occupationally tinal tract in 48 hours and no asbestos fiber release during the use of the prod exposed. There is a 5 to 7 fold increase was detected in the animal tissues a t the uct. The likelihood of such fiber release In lung cancer in asbestos workers which end of 1 week. The gastroinstestinal tract depends predominantly on the ease with is noted as early as 10 to 14 years after of the ra t seemed to provide an effective which the fibers can be dislodged and on onset of exposure and is significant a t 20 barrier to penetration. the degree to which the use of the prod years (Refs. 9 through 15). Seven per In a published study by W. E. Smith, uct destroys the fibers. Almost all as cent of deaths in asbestos workers are et q.1. (Ref .41), hamsters maintained on bestos fiber used in the United States caused by pleural and peritoneal meso a diet of 1 percent chrysotile or amosite for manufacturing products becomes thelioma (Refs. 16 through 33). This is a through life had no gastrointestinal tightly bound within the products and marked increase since this tumor is ex tumors. usually undergoes little actual abrasion tremely rare in the general population. A report by Westlake, Spjut and or wear before being discarded. Asbestos There is suggestive evidence concerning Smith (Ref. 42) indicates th a t the ra t cement products (accounting for most of an increase in the rate of gastrointesti colonic mucosa is penetrated by chryso the asbestos used in the United States), nal malignancies in asbestos workers tile after feeding a diet containing 5 per shingles and floor tiles are in this cate (Ref. 34). cent asbestos for 3 months. gory. Some asbestos-bohtaining products, There is considerable evidence th at Cunningham and Pontefract (Ref. 43 such as brake linings, are subjected to most human lungs harbor thousands or and 44) injected chrysotile fibers (9.4 great friction; their rate of wear is con millions of asbestos fibers although most and 94 x 10') directly into stomachs of siderable, and at times they are almost people do not have asbestosis (Refs. 35 rats. Fibers were found in blood and completely worn away. In the case of through 37). This Is due to the ubiquity other organs, 2-4 days after treatment.. brake linings, the application of force is of the substance. Some of these fibers are Control rats, although having no asbes so intense and the heat created so great chrysotile asbestos, and amphiboles are tos in blood, also had high levels of th at most chrysotile fibers are destroyed probably present also. This number of asbestos in tissues. by bang converted into another sub fibers is relatively small in most persons These workers found that, whereas the stance which is non-fibrous. 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 uncoated in the Ottawa area ranged from 1 to 12 proofing materials is a serious source of fibers, is neede'd 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 band, seems to indicate th a t 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, i t is reasonable facture of asbestos-containing products, asbestos fibers of varying sizes is such to conclude th a t water and many other use of such products, and demolition th at the results obtained in one labora beverages for human consumption con can 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 th a t asbestos sources. Altrnate methods of disposal often result in commingling of asbestos- scientists working in this field is cur rently attempting to develop standard filters may remove some asbestos mate 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 term emission source. identification and qualification of asbes tos fibers. The Environmental Protection tration, asbestos was added to distilled water and dispersed evenly by the action Asbestos fibers thus are ubiquitous in air, water and a large percentage of the Agency is currently investigating four separate techniques in order to establish of an ultrasonic generator. Electron microscopy of this material clearly earth's crust. The amount of this ma terial which additionally is added to the environment and to food and drugs by the use of asbestos filters is not known. Therefore it is obvious th a t the presence the best method for identification, quan tification, sizing and typing of asbestos particles and fibers. At present, the Na tional Institute for Occupational Safety and Health (NIOSH) recommends, as a showed large numbers of asbestos fibers. This material was then filtered through an asbestos filter, and electron micro scopic examination of the filtered mate rial showed a reduction in the number of of asbestos in these products is only one small source of exposure. Asbestos inhalation has been known to be an occupational hazard in workers in asbestos mines. The asbestos is inhaled technique for sampling of air, a method based on counting fibers greater than 5 microns in length .using phase contrast illumination a t 430x magnification with a 4 millimeter objective (Refs. 38 and asbestos fibers. 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 and lodges in the lungs causing the de 39). This technique is currently recom taken by the Food and Drug Administra velopment of a fibrotic disease known as "asbestosis." Asbestosis, or abestoric pneumonoconiosis, was the first clearly demonstrated adverse effect of asbestos in man. I t is characterized by a pattern of roentgenographic changes in the lung consistent with diffuse interstitial fi brosis of variable degree and a t times with fibrosis and calcification of the pleura; clinical changes th at include fine rales, finger clubbing and shortness of breath, each of which may be absent in an individual case; and physiologic changes consistent w itha restrictive lung disorder (Refs. 2 through 8). mended for liquid materials until more accurate and sensitive practical methods are developed. However, as indicated be low, another method is proposed for analysis of asbestos fibers in a material such as talc. The evidence concerning the possible hazard from ingestion of asbestos par ticles is contradictory and inconclusive: In an unpublished study by 1. M. Swinbum (Ref. 40), asbestos particles were fed once a week to SPF Wistar rats for 16 and 18 weeks. The material was administered in butter. Although the par ticles were of the size range known to 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 Anns. Based on phase contrast microscopy, 11 of 13 samples had clearcut 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 th e positive specimens of variable sample size. Using electron microscopy, 12 of the 12 samples examined were positive. Quantitation is not yet complete. In these workers in asbestos mines, malignancies of the lung and of the body produce tumors by. other modes of ad ministration, no tumorgenlc effect was In this survey, seven of 13 manufac turers of parenteral drugs do not use as lining tissues, namely lung cancer and noted. With a single large dose, the fibers bestos filters; four firms use such filters FEDERAL REGISTER, V O L 38 , NO. 188-- FRIDAY, SEPTEMBER 2 8 , 1973 HeinOnline -- 38 Fed. Reg. 27077 1973 27078 PROPOSED RULES followed by final membrane type filters kidneys and occasionally to brain tissue 8. Soper, W. B., "Pulmonary Asbestosis: A (one of these uses asbestos filters for Its rinse water without final filtration of such w ater); and two firms use asbestos filters only for their rinse water, without . final filtration. suggesting th at some asbestos may enter the circulation. Thus, there is experimental evidence th a t parenteral administration of asbes tos fibers may lead to wide dissemination report of a case and a review," Am. Rev. Tuberc, 22:671-684, 1930. 9. Lynch, K. M., and W. A. Smith, "Pul monary Asbestosis m : Carcinoma of lung in asbesto-sillcosls," Am. J. Cancer, 24:60-6-1, 1935. The preliminary report of these studies of such fibers in animals and to the de 10. Doll, R., "Mortality from Lung Cancer is on display a t the Office of the Hearing velopment of local malignant tumors as In Asbestos Workers," Brit. J. Indm tr. Med., Clerk. Any other scientific data in this regard should be submitted to the Hear ing Clerk. Certain parenteral drugs, such as blood fractionation products, may be filtered several times through asbestos filters. Thus far, it is not known with certainly whether the more viscous products could be successfully processed through ter minal membrane filters without com promising safety, identity, strength, quality or purity. The precise effect of asbestos pad filtration on removal of well as malignant mesotheliomas of the pleura and peritoneum similar to those th a t 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 F ederal R egister of April 6 , 1973 (38 F R 8820) national emission standards for asbestos milling and manufacturing based on the determination th a t asbestos 12:81-86, 1955. 11. Buchanan, W. D., "Asbestosis and Primary Intrathoraclc Neoplasms," Ann. N. Y. Acad. Sci., 132:507-518, 1965. 12. Cordova, J. F., H. Tesluk and R. P. Knudtson, "Asbestosis and Carcinomas of the Lung," Cancer, 15:1181-1187, 1962. 13. Gross, P., R. T. P. doTrevlllo, E. B. Tokor, M. Kaschak and M. A. Babyak, "Experimental Asbestosis. The development of lung cancer In rats with pulmonary deposits of chrysotllo asbestos dust," Arch. Environ. Health, 15:343-355,1967. 14. Selikoff, I. J., 3. Churg and E. O. Ham mond, "Asbestos Exposure and Neoplasia," pyrogens (Ref. 46 and 47) is not com pletely known a t the present time. Currently the Food 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 effect of parenteral inoculation of asbestos fibers. In 1958, Schmahl (Ref. 48) reported th at implantation of asbestos' fibers and crumbs in either 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) is a hazardous air pollutant. This stand JAMA, 183:23-26,1964. ard has been developed despite the fact 15. Borow, M., A. Conston, L. L. Llvomeso the EPA also recognizes th a t a, "stand and N. Schalet, "Mesothelioma and Its. Asso ardized references method has not been ciation with Asbestos," JAMA, 291:687-591, 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 1967. 16. Elmes, P. C., W. T. E. McCaughoy and O. L. Wade, "Diffusa Mesothelioma of the Pleura and Asbestos,'".Brit. Med. J., 4:360 353, 1965. prepared subsequent to a meeting spon 17. Elmes, P. C. and O. L. Wade, "Relation sored by the International Agency for ship Between Exposure to Asbestos and Research on Cancer (Ref., 52). The Food Pleura Malignancy In Belfast," Ann. N.Y. and Drug Administration's review of this Acad. Sci., 132:649-567, 1966. , report indicates the following areas of further research are necessary: (1) Fufther epidemiology, particularly with respect to past exposure to asbestos and cancer of sites other than lung, 18. Enticknap, J. B. and W. N. Emlthor, "Peritoneal Tumor In Asbestosis," Brit. J. Ind. Med., 21:20-31, 1964. 19. Fowler, p . B. S., J. O. Eloper and E. C. Warner, "Exposure to Asbestos and Meso thelioma of th e Pleura," Brit. Med. J., 2:211 pleura, and peritoneum. 213, 1964. (a) following fiber. Assessment of excess cancer exposure to, only one type ` orifsksCInh2ut0hr.geH, U"aNmneimtoepodlnaSdsi,taaEtAe.smCwo.,nigtIh.In3Ss.pueSlcaeitlaiikol onRfofWfaeojnrokdnecr3os. to Intraabdominal Neoplasia," Ann. N.Y. have performed a number of studies in '(b ) Investigation of whether reduc Acad. Sci., 132:519-525, 1965. which asbestos fibers were injected sub tion of asbestos exposure in lungs below 21. Hourihane, D. O'B., "Tho Pathology of cutaneously (Ref. 49) into the flanks of mice. In the first experiments, crocidolite, amosite and chrysotile asbestos fi bers were used and each animal was in jected twice subcutaneously in both ' those causing asbestosis abolishes excess Mesothelioma and an Analysis of Their As risk of carcinoma. . ~ (c) Investigation of evidence of creased risk of cancer resulting from sociation with Asbestos Exposure," Thorax, aans i n 1th9e2:2l2i6.o8mL-2al7e8ba,ennd1,96AJ4s..beasntdos H. Plstawkft, "Meso Exposure," Arch. En bestos in water, beverages, food, or viron. Health, 14:659-663, 1967. ' flanks with 10 milligrams of fibers in liquids used for the administration of 23. Mann, R. H,, J. L. Grosh and W. M. saline with an interval of five weeks be drugs. ' O'Donnell, "Mesothelioma Associated with tween the injections. Seven of seventyone mice which survived 40 weeks or more developed injection site tumors. In addition, one mouse developed a meso thelioma of the peritoneum underlying (2) Development of methods of quan titative assessment, size analysis and characterization of particles .and fibers. References Asbestosis," Cancer, 19:621-526, 1966. 24. McCaughey, W. T. E,, O. L. Wade and P. C. Elmes, "Exposure to Asbestos Dust and Diffuse Pleural Mesotheliomas," Brit. Med. J., 2:1397,1962. 25. McDonald, A. D., A. Harper, O. A. Elat- the injection site. The injection site sarcomas were produced by all three types of fibers. In addition, Roe ef al (Ref. 49) showed th at the asbestos fibers were widely 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 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. 2. Cooke, W. E., "Fibrosis of the Lungs due to the Inhalation of Asbestos Dust," Brit. Med. J., 2:147, 1924. ta r and J. C. McDonald, "Epidemiology of Primary Malignant Mesothellal Tumors In Canada," Cancer, 25:914-919, 1970. 26. Newhouse, M. L. and H. Thompson, "Epidemiology of Mesothellal Tumors in tho London Area," N.Y. Acad. Set., 432:579-600, 1965. 3. Cooke, W. E., "Pulmonary Asbestosis," Brit. Med. J., 2:1024-1025.1927. 4. ' Dreessen, W. C., J. M. Dallavalle, T. Edwards, J. W. Miller, and R. R. Sayers, "A .Study of Asbestos In the Asbestos Textile Industry," Public Health Bull., 241, Washing ton, TJB. Government Printing Office, 1938, 126 pp. ' 27. Owen, W. G., "Mesothellal Tumors and SELcx.ip.,o4su3r2e:6t7o4-A6s7b9e,s1to9s65D. ust," Ann. > N.Y, Acad. 28. Selikoff, L. J., J. Churg and E. C. Ham mond, "Relation Between Exposure to As bestos and Mesothelioma," New Eng. J. Med., 272:660-565,1965. of 71 mice, malignant mesotheliomas of 5. McDonald, S., "History of Pulmonary 29. Wright, G. W., "Asbestos and Health In the thorax and/or abdomen developed. Asbestosis," Brit. Med. J., 2:1025-1026, 1927. 1969," Am. Rev. Resp. Die., 409:467-479, 1969. In a later study (Ref. 51) Kanazawa 6. Merewether, E. R. A., "The Occurrence 30. Selikoff, L. J., E. C. Hammond and 3. et al showed that, after subcutaneous injection of asbestos fibers in mice, fibers could be found to have disseminated to of Pulmonary Fibrosis and Other Pulmonary Affections in Asbestos Workers," J. Ind. Hyg., 12:198-222 and 12:239-257,1930. 7. Lillis, R. G., "Pulmonary Asbestosis: Re Churg, "Asbestco Exposure, Smoking, and Neoplasia," JAMA, 204:106-112,1968. 31. Wagner, 3. C., C. A. Sleggs and P. Mar chand, "Diffuse Pleural Mesothelioma and regional and distant lymph nodes, spleen, port of a case," Minn. Med., 13:495-499,1930. Asbestos Exposure In the North Western Capo FEDERAL REGISTER, VOL. 38,- NO. 188-- FRIDAY, SEPTEMBER 28 , 1973 HeinOnline -- 38 Fed. Reg. 27078 1973 PROPOSED RULES 27079 Province," Brit. J. Ind. Med., 17:260-271, 52. "Report of the Advisory Committee onbrane filters, is also requested. Finally, 1960. 32. Champion, P., "Two Cases of Malig n an t Mesothelioma after Exposure to As b e s t o s , Am. Rev. Resp. Bis., 103:821-826, 1971. 33. Selikoff, L. J. and E. C. Hammond, "En vironmental Epidemiology, m . Community Asbestos Cancers to th e Director cl the In ternational Agency fo r Research o n Cancer," Brit.J.Industr.M cd., 30:180-186,1073. The Commissioner recognizes th at It Is not possible to eliminate all sources of asbestos contact with food and drugs. comment on methods of quantitative assessment, size analysis, and char acterization of particles and fibers, is essential in order to develop final methods on which accurate and fair compliance can be based. Effects of Nonoccupational Environmental Asbestos Is used In virtually all pipes Therefore, pursuant to provisions of Asbestos Exposure," Am. J. Pub. Health, 5S: carrying drinking water, in buildings in the Federal Food, Drug, and Cosmetic 1658-1666, 1968. which food and drugs are manufactured, Act (secs. 402, 502, 701, 52 Stat. 1046 34. Wagner, J. C., "Epidemiology of Diffuse Mesothelial Tumors: Evidence of an -Asso ciation from Studies In South Africa and th e United Kingdom," Ann. N.Y. Acad. Sei., 132:575-578, 1965. 35. Churg, J., E. C. Hammond, A. M. and in many filtering systems used in the manufacture of food and drugs, and is found in some substances, notably water and talc, used in the manufacture and processing of food and drugs. Neverthe 1047, as amended, 1050-1051, as amended, 1055-1056, as amended; 21 UJS.C. 342, 352, 371) and under authority delegated to him (21CFR 2.120), the Commissioner of Food and Drugs proposes to amend Langes, W. J. Nicholson, L. J. Selikoff and less, the Commissioner also recognizes Title 21 of the Code of Federal Regula Y. Suzuki, "Biological Effects of Asbestos," th a t asbestos fibers perform no functional tions as follows: presented a t the National Institutes of Health, Peb. 1,1973. 36. Anvilvel, L. and W. M. Thurlbeck, "The Incidence of Asbestos Bodies in th e Lungs a t Random Necrospsies In Montreal," Can. Med. purpose in talc and are an unnecessary contaminant. I t is therefore reasonable to require precautions to be taken in the manufacture of food and drugs, os p art of 1. In P art 121 by amending 121.101 (d) (8) by alphabetically adding to the table a new item and in paragraphs (h> and (1) by revising the entry for "talc", Assoc. J., 95:1179-1182,1966. good manufacturing practices, to assure to read as follows: 37. Cauna, D., R. S. Totten and P. Gross, "Asbestos Bodies in Human Lungs a t Au topsy," JAMA,192: 371-373,1965. . 38. "Criteria for a Recommended Stand ard--Occupational Exposure to Asbestos," Report of Review Committee, National In th a t 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 ing action: 121.101 Substances that are generallyrecognized as safe. * * * * * <d) * * stitute for Occupational Safety and Health, 1. In view of the demonstrated hazard Publication No. HSM 72-10267 (1972). in animals from injection of asbestos 39. Lynch, J. R. and H. E. Ayer, "Measure fibers, th e Commissioner is proposing th at Prc-lEii Tckranco Lirmeoittarttitolonsiuc-r m ent of Asbestos Exposure," J. Occup. Med., 10: 21-24,1968. 40. Swinburne, L. M., "The Ingestion of as bestos by rats (unpublished d ata)," personal communication to Bureau of Foods, EDA. 41. Smith, W. E,, L. Miller, R. E. Elssser and the good manufacturing practice (GMP) regulations for drugs be amended to re quire th at filtration procedures for pa rental drugs shall utilize either a non asbestos-containing or non-fiber-releas (*) JitFCcoa'oi-d'ilrl.ktr'loncTrraCeofXoBe.coSodtI D. D. Hubert, "Tests for Carcinogenicity of ing filter such as a membrane filter or, if Asbestos," Ann. N.Y. Acad. Sei., 132:456-488, 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," Lab. In an asbestos-containing filter is neces sary, shall also utilize an additional non asbestos-containing or non-fiber-releas ing filter such as a membrane filter to reduce asbestos fiber content to the min To!r(trccoXc3bx:!c3 _________ In ctowinj gnm Ei1Li2oi1co.c2d0S3i0n0d}r.ier- - bsi3asicfassntaIEnckdsirB0c35coadngieant xcafcoaZjedsin.s feed vest., 14:2029--2033, 1965. imum level feasible unless such a subse 43. Cunningham, H. M. and R. Pontefract: quent filter will compromise the safety, (a) "Asbestos Fibers in Beverages and identity, strength, quality or purity of (h) Drinking Water," Nature, 232:332-333, 1971. (b) "Symposium o n Industrial Chemicals as Food Contaminants," Journal of the AOAC, 56:976-981,1973. the product. 2. The Commissioner intends to pro mulgate a final regulation for talc under Talc (free of asbestos libers as determined in 5 121.2006) . * a * -44. Pontefract, R. and H. M. Cunningham: "Penetration of Asbestos through the Diges tive Tract of Rats," Nature, 243:352-353, 1973. 45. Nicholson, W. J., C. J . Maggiare and I. J. Selikoff, "Asbestos Contamination of Parenteral Drugs, Science, 277:171-173, 1972. ' 46. Tui, C. and A. M. Wright, "The Pene 121.2006 as soon as a method for deter mining asbestos fibers in food-grade talc is validated. Such a method is proposed below, as part of a republication of the earlier proposal in which no methodology was specified. The Commissioner con cludes th at a final regulation for talc <!)** Tala (free of asbestos libers as determined in $ 1 2 1 .2 0 0 6 ), m* mm 2. In P art 121 by amending Subpart E by adding the following new section: tration of Non-Pyrogen Infusion and Other Intravenous Fluids by Absorptive Filtration," under T art 121 cannot be promulgated until a reproducible and accurate method 121.2006 Talc. Annals Surg., 226:412-425,1942. can be specified for compliance purposes. (a) Talc is a naturally occurring 47. Remington's Pharmaceutical Sciences, "Parenteral Preparations, Pyrogens," Chap ter 82,14th Ed. (pg. 1524), 1970. 48. SchmShl, D-, "Cancerogene Wirkung von Asbest bei Implantation von Ratten," 3. The Commissioner is also proposing that any talc used in the manufacture or processing of drugs meet the specifica tions for this substance th a t will be Im hydrous magnesium silicate subject to a prior sanction for use in coating pol ished rice. I t is found in natural deposits th at may be contaminated with asbestos Zeitschrift f r Krebsforschung, 62:561-567, posed by 121.2006. fibers. 1958. 4. The Commissioner realizes th a t the (b) Good manufacturing practice re 49. Harington, J. S. and F. J. C. Roe, "Stud ies of Carcinogenesis of Asbestos Fibers and their Natural Fibers," Annals of the N.Y. Academy o f Sciences, 232:439-450,1965. 50. Roe, F .J.C ..R .L . Carter, M. A. Walters and J. S. Harington, "The Pathological Ef fects of Subcutaneous Injections of Asbestos issues raised in this notice are complex and have widespread ramifications. Com ment is requested on all aspects of the public health significance of ingestion and injection of asbestos fibers. Since adoption of any new filtration require quires th a t talc be free from asbestos fibers to the maximum extent prac ticable. Accordingly, any food or food packaging material containing talc that is no t free from asbestos fibers as deter Fibers in Mice: Migration of Fibers to Sub- ments may require use of additional mined by th e method set out in para mesothelial Tissues and Induction of Mesotheliomata," In t. J . of Cancer, 2:628-638, 1967. , 51. Kanazawa, K., M. S. C. Birbeck, R. L. Carter andF . 3. C. Roe, "Migration of Asbes tos Fibres from Subcutaneous Injection Sites in Mice," British Journal of Cancer, 24:96 equipment, comment on the availability of appropriate equipment, the need for use of asbestos-containing filters as con trasted with filters which contain no asbestos, and the time needed to ob tain and begin using non-asbestos- graph (c) shall be deemed to be adul terated In violation of section 402(a) (1) of the act. (c) The following method shall be used to determine compliance with this 106,1970. containing final filters such as mem section: No. 188--Pt. 1- FEDERAL REGISTER, V O L 3 8 , NO. 188-- FRIDAY, SEPTEMBER 2 8 , 1973 HeinOnline -- 38 Fed. Reg. 27079 1973 27080 PROPOSED RULES (1) The various kinds of asbestos are limit for the presence of these asbestos a t least 99.99 percent free of chrysotilo distinguished from talc and from each fibers in talc. These limits assure a asbestos fibers. other by their refractive indices, other purity of talc a t least 99.9 percent free (3) Optical crystallographio charac optical crystallographic properties, and of amphibole types of asbestos fibers and teristics of asbestos minerals and talo: morphology as determined with a polar Examples or Kefkactive Indices (n) izing microscope (Methods of the Asso ciation of Official Analytical Chemists, 11th Ed., 1970, Sections 36.541-36.543, Substance nS Extinction Elongation p. 717-7211.1 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 1.590, beta being very close to gamma. All of the principal refractive indices of chrysotile are less than 1.590. Chrysotile asbestos is therefore distinguishable from fibrous looking talc particles in a ;1.574 refractive index liquid and the Actinolite__ _ Amosite-- V.:. AnthophyllltO- C h ry so tile.. : 1.614 1. 615-1.655 . 1.663 ; 1.675 . . 1.598 1.698 ; 1. 593-1.674 1.603 . 1.619 1. 619-1.633 1.629 1.633 . 1.493 1.608 1.630 1.641 In clin ed .. L 625-1.605 1.64-111,.. 63 680 702 ................... . . 1.623 . 1. 623 P arallel.. ................. . 1.605-1.635 1.615-1. 697 ................... 1. 6 31.................. E63" 1. 640 .................. 1.630-1.642 1.635 1.633 1.601 1.640-11..665170..................................... 11.. 652 617 .................. P arallel. 1.612 1.622 . Positivo. Positivo. r Positivo. other five amphibole types of fibrous asbestos from talc in a 1.590 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, Crocldolite.. 1. 529-1.659 1.530-1.664 1.537-1.667 1. 6 3 - 1.54 : 1 .5 4 -1 .5 5 1.642 . 1.655 1.642 1.543 (calo.) 1*655 ....................................... . 1.646 1.650 1.657 ....................................... 1.546 1.657 1.657 ....................................... 1.548 1.660 1.560 ....................................... 1.695 , 1.693 1.695 1.697 ....................................... 1.697 1.700 1.703 ....................................... 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 /im or longer. (2) 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 1.590 liquid, and place on each a square or rectangular cover glass suffi- Talc_____ Tremolito i. . 1.638-1.545 . 1.639 1.539 1.639 1.640 1.641 1.544 L545- . 1.699 1.699 1.699-1.612 1.600 1.602 1.602 1.602-1.623 1.601 1.601 1.609 1.609 1.575-1.690 P a ra lle l or V o r S'-- 1 689 1.5S 9...................................... 1.689 1.6S 9....................................... 1.689 1 .5 S 9....................................... n carly -n 1.675 ....................................... 1.635 1.535 ....................................... 1.692 1.592 ....................................... 1.691 1.634 11..553944 ....................................... ....................................... 1.613 1.625 In o lln cd...........: ......... 1.613 1.625 ....................................... 1.613-1.626 1.625-1.637 ....................................... 1.616 1.627 ....................................... 1.614 1.035 ....................................... 1.618 1 .6 3 1 ....................................... 1.613-1.633 1.624-1.650 .......... ............................. 1.612 1.623 ....................................... 1.617 1.630 ....................................... 1.622 1.630 ....................................... 1.623 1.630 ....................................... ciently large so th at the liquid will not 1.613 1.621 1 .6 3 4....................................... run out from the edge (ca. 18 mm. square) and will provide a uniform par n+n. ticle distribution. Fibers counted by this 2 method should meet the following cri 3. In P art 133 by adding the following ber-releasing filter may be used in tho teria: (i) Length to width ratio of 3 or new paragraph (i) to 133.6 to read as manufacture of a parenteral drag or par greater (ii) length of 5 jam or greater follows: (iii) width of 5 /im or less. Count and record the number of asbestos fibers 133.6 Components. found in each 1 milligram as determined * * * * " * enteral drag ingredient unless it is not possible to manufacture th at drug or drag ingredient without the use of such a filter. If use of such a filter is required, from a scan of both slides with a polariz (i) Talc is a naturally occurring hy an additional non-asbestos-containing ing microscope a t a magnification of ap drous magnesium silicate which may or non-fiber-releasing filter such as a proximately 400 X. In the 1.574 refrac reasonably be expected to contain as membrane filter shall subsequently bo tive index liquid, chrysotile fibers with bestos fibers which may be injurious to used to reduce the content of any asbes Indices less than 1.574 in both extinction' health. Current methodology cannot as tos-form particles in the drug or drag in positions may be present; in the 1.590 sure the absence of asbestos in talc. gredient. Evidence for reduction shall bo refractive index liquid, the other five Accordingly, any drug, drug ingredient, based on the use of the methods de amphibole types of asbestos fibers with or drug packaging material containing scribed in "Criteria for a Recom indices exceeding 1.590 in both extinc talc th at fails to meet the specifications mended Standard--Occupational Expo tion positions may be present. Check the of paragraph (c) of 121.2006 of this sine to Asbestos," Report of Review Com extinction and sign of elongation for chapter as determined by the method mittee, National Institute for Occupa 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 not more than 1000 amphibole types of asbestos fibers and not more than 100 chrysotile asbestos fibers per milligram-slide constitutes the maximum set out in th at paragraph shall be deemed to be adulterated in violation of section 501(a) of the Act. 4. By adding the following new para graph (j) to 133.8 to read as follows: 133.8 Production and control proce *dures. * * - '* * (j) Use of asbestos-containing filters: tional Safety and Health, Publication No, HSM 72-10267 (1972).3Use of an asbes tos-containing filter without subsequent use of an additional non-asbestos-con taining membrane filter is permissible only upon submission of proof to tho Food and Drag Administration th at uso of a non-asbestos-containing membrane Filters used in the manufacture of a 1Copies may be obtained from: Association of Official Analytical Chemists P.O. Box 540, Benjamin Franklin Station parenteral drug or parenteral drag in gredient shall not release fibers into such Copies may bo obtained from: Superintendent of Documents TJ.S. Government Printing Office Washington, DC 20044 products. No asbestos-containing or fi Washington, DC 20402 FEDERAL REGISTER, VOL. 38 , NO. 188-- FRIDAY, SEPTEMBER 28 , 1973 HeinOnline -- 38 Fed. Reg. 27080 1973 PROPOSED RULES 270S1 filter -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, Hood and Drug Administration, E m . 6-86, 5600 shers Lane, Rockville, MD 20852, -written comments (prefer ably in quintuplicate) regarding the pe . tition and the Commissioner's proposal. Comments may be accompanied by a ,,memorandum or brief in support thereof. The 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. F art 71 of the Federal Aviation Regu lations th at would alter several VOR Federal Airways in the vicinity of Chi cago, 111., due to the planned decommis sioning of the Naperville, HI., VOR. Interested persons may participate in the proposed rule making by submitting such written data, views or arguments as- they may desire. Communications should identify the airspace docket num ber and be submitted in triplicate to the Director, Great Lakes Region, Attention: Chief, Air Traffic Division, Federal Avia tion Administration, 2300 East Devon, Des Plaines, HI. 60018. All communica tions received on or before October 29, 1973, will be considered before action is thence via INT DuPage 346T(344`M) radials, and Oshkosh, Wis. 1370T<185 M) radials, to Oshkosh. The Naperville VOR win be decommis sioned about June of 1974 due to the in creased cost of lease renewal of the Na perville site, and the future detrimental ' effect th a t buildings planned for th e vi cinity would have on the NAVAID. The DuPage VOR win be frequency protected so th a t it can serve in the airway struc ture. Some of the airways in this vicin ity would be realigned via DuPage in lieu of Napervnie. This amendment is proposed under the authority of Sec. 307(a) of th e Federal Aviation Act of 1958 (49 TLS.C. 1348(a)) Dated September 24, 1973. taken on the proposed amendment. The and Sec. 6(c) of' the Department of A. M. S chmidt, Commissioner of Food and Drugs. [FR Doc.73-20711 F Jle 9 -2 7 -7 3 ;8 :4 5 am] proposal contained in this notice may be Transportation Act (49 TLS.C, 1655(c)). changed in the light of comments received. An official docket will be available for Issued in Washington, D.C, on Septem ber 20, 1973. examination by interested persons a t Chatxes H . Newpoe, Social and Rehabilitation Service [ 45 CFR P art 221 ] the Federal Aviation Administration, Office of the General Counsel, Attention: Rules Docket, 800 Independence Avenue Acting Chief, Airspace and Air Traffic Rules Division. [FR Doc.73-20703 Filed 0-27-73;8:45 am i FAMILIES, CHILDREN, AGED, BLIND, OR SW , Washington, D.C. 20591. An infor - DISABLED INDIVIDUALS mal docket also will be available for Service Programs; Correction . FR Doc. 73-19242, published a t page 24872 in the issue dated Monday, Sep examination a t the office of the Regional Air Traffic Division Chief. The proposed amendment would: 1. Realign V-6 from Cordova, Hi., via [ 1 4 CFR P art 7 5 ] [AirJpaco Docket Ho. 73-772-10] AREA HIGH ROUTE tember 10,1973, is corrected by changing: INT Cordova 087T(083M) and DuPage, Proposed Alteration 1. The number "233" in item number two of the preamble, fifth, line, to "233y3" ; 2. The code designation "221.6(a) (3) (i) " in item number two of the preamble, seventh line, to '"221.6(c) (3) (i) 3. The code designation "211.6(a) (3) (iii) " in item number three of the pre amble, fourth line, to "221.6(c) (3) (iii)"; 4. The code designation "211.6(a) (3) (vii) " in item number four of the pream ble, fourth line, to "221.6(c) (3) (vii) 5. The code designation "211.7(b)" in item number five ofth e preamble, fourth line, to "221.7(b) " ; 6. The code designation "211.9(b) (3)" in item number-seven of the preamble, sixthline, 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. T he number "8" in 221.6(a) (4), (now corrected to 1221.6(c) (4)), fourth line, to "6"; and 9. The word "secured" in 221.9(b) (5) .fourthline, to "secure". Approved September24,1973. T homas S. M cF ee, Deputy Assistant Secretary for Management Planning and Technology. [FR Doc.73-20726 Filed 9-27-73:8:45 am] DEPARTMENT OF TRANSPORTATION HI., 255T(253M radials to DuPage. From the INT of Chicago Heights, HI., 358tT(356M) and South Bend, Ind., 271T(271M) radials to South Bend. 2. Realign V-8 from Cordova, HI., via INT Cordova 087T(083M) and Joliet, HI., 291T(289eM) radials to Joliet. 3. Realign V-9 from Joliet, HL, via INT Joliet 329CT(327M) and Milwaukee, Wis., 209T(207M) radials to MilwaukcG* 4! Designate new VOR Federal Airway V-9 west alternate from Pontiac, HI., via INT Pontiac 345CT(343M) and Milwau kee, Wis., 209CT(207M) radials to Mil waukee. 5. a. Realign V-10 from piano, HI., in tersection direct to Chicago, O'Hare, Hi. b. Delete th a t portion of V-10 which lies between Plano intersection and Niles, HI., intersection. 6. Delete th at portion of V-10N which lies from Naperville via Neptune, Ind., intersection to South Bend. 7. Delete V-97 from Chicago Heights, HI., via Joliet, HI., to Woodstock, HI., intersection. 8. Realign V-97 from Northbrook, HI., direct to Janesville, Wis. 9. Realign V-100 from Rockford, HL, to Northbrook, HI., via INT Rockford 080T(077M) , and Northbrooks 292T (290-AD radials. , 10. Delete V-116 from Joliet, HI., to Neptune, Mich., intersection. _ 11. Delete V-116S from Naperville, HI., via Grand Beach, Ind., to Keeler, Ind. 12. Realign V-177 from DuPage, HI., The Federal Aviation Administration. (FAA) is considering an amendment to P art 75 of the Federal Aviation Regula- . tions th at would realign a segment of J-938R from Reno, Nev, to Maple, Calif. Interested parsons may patieipate in the proposed rule making by submitting such written data, views or arguments as they may desire. Communications should Identify the airspace docket number and ha submitted In triplicate to the Direc tor, Western Region, Attention: Chief, Air Traffic Division, Federal Aviation Administration, 1500 Aviation Boule vard, P.O. Box 92007, Woridway Postal Center, Los Angeles, Calif. 90009. All communications received on or before October 29, 1973, will be considered be fore action is taken on the proposed amendment. The proposal contained in this notice may be changed in the light of comments received. . An official docket will be available for examination by interested parsons a t the Federal Aviation Administration, Office of the General Counsel, Attention: Rules Docket, 800 Independence Avenue SW , Washington, D.C. 20591- An informal docket also will be available for examina tion a t the office of the Regional `Air Traffic Division Chief. As p art of this proposal relates to the navigable airspace outside the United States, this notice is submitted in con sonance with the ICAO International Standards and Recommended Practices. Applicability of international Stand Federal Aviation Administration direct to Janesville, Wis. ards and Recommended Practices by the [1 4 CFRPart 713 [Airspace DocketHo. 73-GL-44] VOR FEDERAL AIRWAYS 13. Delete V-218 from Rockford, HI., Air Traffic Service, FAA, in areas outside to Keeler, Mich. domestic airspace of th e United States 14. Realign V-227 from Pontiac, HI., Is governed by Article 12 of and Annex direct to Rockford, HL 11 to th e Convention on International Proposed Alteration 15. Realign V-429 from Joliet, HI., via Civil Aviation, which, pertain to the The Federal Aviation Administration INT Joliet 351*T(349*M) and DuPage, establishment of air navigation facilities (FAA) is considering an amendment to HI., 185T(183*M) radials, to DuPage, and services necessary to promoting the FEDERAL REGISTER, V O L 38 , NO. 188-- FRIDAY, SEPTEMBER 2 8 , 1973 HeinOnline -- 38 Fed. Reg. 27081 1973