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Laj THIS WAS NOT A RECORD OF nU s --a PE. ,GutISNDAUNSDTRCIAENISNN,,COI.NTDCBIDE ANUOTTHCEONMTE'''AFTREODM Jl_ J j.i., . * REVISED RECOMMENDED ASBESTOS STANDARD PD U. S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE Public Health Service Center for Disease Control National Institute for Occupational Safety and Health j bB 0005135^ Pi REVISED RECOMMENDED ASBESTOS STANDARD r \ U. S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE Public Health Service Center for Disease Control National Institute for Occupational Safety and Health DECEMBER 1976 For oat* by tlw Suparintandani of Docraanu, U.S. Ggnmiu Printing OMlca. Woihlnaton. D.C. 2CM03 ( | .^ 31 3 l_BB_005186 J The Division of Surveillance, Hazard Evaluations, and Field Studies, National Institute for Occupational Safety and Health (NIOSH), having primary responsibility for development of a NIOSH position paper on health effects of occupational asbestos exposure, has critiqued all available data and prepared the following document for publication and transmittal to the Occupational Safety and Health Administration (OSHA), as requested by the Assistant Secretary of Labor. Primary responsibility for development of this document was shared by Richard A. Lemen and John M. Dement, with technical consultation provided by Dr. Joseph K. Wagoner. Individuals who served as the NIOSH review committee were:* Kenneth Bridbord, M.D David H. Groth, M.D. Gerald J. Karches James B. Lucas, M.D. James H. Wills, Ph.D. DHEW (NIOSH) Publication No. 77-169 ii bb" 0005137_J REVISED RECOMMENDED ASBESTOS STANDARD Table of Contents I. INTRODUCTION II. BIOLOGIC EFFECTS OF EXPOSURE ON ANIMALS Carcinogenicity Mutagenicity References Summary Table of Asbestos-Induced Carcinogenicity In Animals Tables and Figure III. EFFECTS ON HUMANS Nonmalignant Respiratory Disease Carcinogenicity Synergism Fiber Analysis In Tissue References Tables IV. SAMPLING METHODS AND ENVIRONMENTALDATA Review of Sampling and Analysis Techniques for Asbestos Comparisons of Asbestos Mass Concentrations (mg/m3) and Fiber Number Concentrations(flbers/cc) Nonoccupatlonal Exposures - AmbientLevels References Tables V. BASIS FOR THE RECOMMENDED STANDARD VI. THE RECOMMENDED STANDARD References Table 1 3 3 12 13 17 21 26 26 30 38 39 A3 53 58 58 71 73 78 82 88 92 GG \A315_ 7B70005lBil I. INTRODUCTION When Che asbestos criteria document was first published in 1972, the National Institute for Occupational Safety and Health (NIOSH) recommended a standard of 2.0 asbestos fibers/cubic centimeter (cc) of air based on a count of fibers greater than 5 micrometers (/an) in length. This standard was recommended with the stated belief that it would "prevent" asbestosis and with the open recognition that it would not "prevent" asbestos-induced neoplasms. Furthermore, data were presented which supported the fact that technology was available to achieve that standard and that the criteria would be subject to review and revision as necessary. Since the time that the asbestos criteria were published in 1972, sufficient additional data regarding asbestos-related disease have been developed.-, . warrant, reevaluation On June 7, 1972, the Occupational . (OSHA) promulgated a standard for occupational exposure to asbestos containing an 8-hour time-weighted average (TWA) concentration exposure limit of 5 fibers longer than 5 ^m/cc of air, with a ceiling limitation against any exposure in excess of 10 such fibers/cc. The standard further provided that the 8-hour TWA was to be reduced to 2 fibers/cc on July 1, 1976 As the result of a court case, OSHA-decided that to achieve the most feasible occupational health protection, a reexamination of the standard's general premises and general structure was necessary. To this end, on October 9, 1975, OSHA announced a proposed rule-making to lower the exposure limit to an 8-hour TWA concentration of 0.5 asbestos fibers longer ; 3J 1 | BB 0005189 than 5 jm/cc of air with a ceiling concentrati n of 5 fibers/cc of air determined by a sampling period of up to 15 minutes. On December 2, 1975, OSHA requested N10SH to reevaluate the information available on the health effects of occupational exposure to asbestos fibers and to advise OSHA on the results of this study. This document contains an updated review of the available information on the health effects of exposure to asbestos. In addition, NIOSH's proposal for a new numerical exposure limit is Included. _J^\^>John F. Finklea, M.D. Director, National Institute for Occupational Safety and Health 2 II. BIOLOGIC EFFECTS OF EXPOSURE ON ANIMALS Carcinogenicity r The carcinogenicity of asbestos was studied through various routes of exposure (a) Instillation (1) Intratracheal Injection P. ' A; !-T1fi 1 H 0!D This technique has been used to study co-carcinogenesis of chrysotile asbestos with benzo(a)pyrene in hamsters (Miller et al, 1965) and rats (Vosamae, 1972; Pylev., 1972; Pylev and Shabad, 1973; Shabad et al, 1974). In both species, it was demonstrated that the effect of chrysotile was additive to that of benzo(a)pyrene for tumors of the respiratory tract. Shabad et al (1974) showed that intratracheal injection of 2 mg of Russian chrysotile on which 0.144 mg benzo(a)pyrene was absorbed (3 times . at monthly intervals), or 2 mg of Russian chrysotile together with 5 mg benzo(a)pyrene (single injection) produced lung papillomas, epidermoid carcinomas, reticulosarcomas, or pleural mesotheliomas in 6/21 and 6/11 rats, respectively, within 9-28 months. No lung tumors or mesotheliomas occurred in 49 rats given 3 doses of 2 mg chrysotile alone or in 19 rats given a single dose of 5 mg benzo(a)pyrene alone during or up to 28 months of observation. (2) Intraperitoneal (ip) Administration Reeves et al (1971) gave ip injections of 0.3, 0.5, or 1.0 ml of a solution of 20 mg/ml amosite, crocidolite or chrysotile to groups of 11, 13, and 13 Charles River CD rats, respectively. Three peritoneal mesotheliomas were observed with chrysotile, three with crocidolite, and 3 GG 14318 7 BB 000519J_| none with amosite after 7-17 months. No data on control animals were reported. Maltoni and Annoscla (1973) Injected 25 mg of crocidolite into 50 male and 50 female Sprague-Dawley rats, 18 weeks old, and later observed 65 mesothellomas-31 In males and 34 in females. Pott and Friedrichs (1972) and Pott et al (1974) injected fibrous and granular dusts into the peritoneal cavities of Wistar rats. The dosage, number of inoculations, and resul and II-2. NOT V 1 i ! After injection of powdered chrysotile, the latent period for the induction of tumors was found to be longer than that after injection of standard chrysotile. The rate of tumor occurrence was about 40% in both groups and was not distinctly influenced by the addition of benzo(a)pyrene. In another group, benzo(a)pyrene without asbestos Induced tumors in 10% of the animals. Histologically, the types of tumors observed were connected with structures of the abdominal wall, including the serosa, and in Isolated cases with those of the intestinal wall (Pott et al, 1972). (3) Intrapleural Administration All commercial types of asbestos have produced mesotheliomas in CD Wistar rats. A dose of 20 mg of the 5 UICC standard reference samples produced mesotheliomas in varying numbers - crocidolite, (61%); amosite, (36%); anthophyllite, (34%); Canadian chrysotile, (30%); Rhodesian chrysotile, (19%) (Wagner et al, 1974). The lowest dose used (0.5 mg chrysotile or crocidolite) produced mesotheliomas (Wagner et al, 1973). Stanton and Wrench (1972), using a dose of 40 mg asbestos dust on gelatin- coated fiber glass pledgets, found that three of the UICC samples, 4 rST.!2L NOT COME FROM PPG FILES (# crocidolite, amosite and Rhod sian chrysotile, all produced mesotheliomas in about 60% of the Osborne-Mendel rats. Pylev and Shabad (1973) induced mesotheliomas with 60 mg of Russian chrysotile. In all these studies there was a long latent period between inoculation and appearance of the tumors. Evidence that the response was dose-related was provided by Wagner et al (1973) and by Stanton (1973). Mesotheliomas have also been produced by other workers: in rats (Donna, 1970; Reeves et al, 1971), in hamsters (Smith et al, 1965) and in rabbits (Reeves et al, 1971). Groth et al (1975) reported no mesotheliomas or other neoplasms from chrysotile in 45 female discard-breeder albino rats, approximately 10 months old. However, all surviving tumor-free animals were killed at 90 or 150 days after injection--a time period insufficient for the development of mesotheliomas as demonstrated by the experiments of Wagner and Berry (1969), The suggestion has been made that natural oils and waxes (Harrington, 1962) and contaminant oils from milling of the asbestos fiber (Harrington and Roe, 1965; Roe et al, 1966) or from plastic storage bags (Commins and Gibbs, 1969) contributed to the incidence of pleural tumors. However, samples from which the oils had been removed gave very similar results to untreated fiber (Wagner and Berry, 1969; Wagner et al, 1973). Morgan and Holmes (1970) and Morgan et al (1971) showed that when asbestos was injected intrapleurally, the majority of the fibers were cleared from the lungs during the first 10 days; subsequently there was also a very slow elimination through the gut. In feeding experiments almost all of the fibers were eliminated. After intrapleural or subcutaneous inoculation, only a minute fraction of the finer fibers were translocated through the tissues. This finding was supported by the 5 studies of Kanazawa et al (1970). The fiber diameter, length, and shape may be important in disease production. All of the eight separate sub-samples which were pooled in the UICC Canadian chrysotile reference sample (Timbrell and Rendall, 1972), when ground separately to a finer powder, produced a higher incidence of mesothelioma than the pooled sample. The highest incidence (66%) was produced by a separate superfine chrysotile sample (20 mg dose) fractionated from fine grade asbestos by water sedimentation (Wagner et al, 1973). Using UICC crocidolite, Stanton and Wrench (1972) found that partially pulverized material gave fewer mesotheliomas than did the standard unpulverized fiber. Prolonged fine grinding is known to destroy fiber and crystalline structure (Occella and Maddalon, 1963). Stanton o CO LU Q __1 UJ aU0--%*-"?; cu 'Ol. cr '-J CZ 5 V/ ; -,i (1973) showed that fibers of other materials, including glass, could induce mesotheliomas, but only when the diameter was of the same order as that of asbestos when measured by light microscopy. In addition to the UICC standard reference samples, other fibers were injected intrapleurally into rats by Wagner et al (1973). Out of a group of 32 rats, mestheliomas occurred in 18 animals injected with a sample of brucite, 3 injected with a ceramic fiber, 1 each with barium sulphate, glass powder, and aluminum oxide. None occurred with a coarse glass fiber. Wagner et al (1976) conducted a series of experiments comparing the biologic effects of a pure asbestos-free cosmetic talc with the superfine chrysotile asbestos used in previous experiments. In an intrapleural inoculation experiment, 48 rats were inoculated with each dust. Eighteen rats of the chrysotile group developed mesotheliomas, but 6 _________ | BB 0005194^2 no tumors were seen in those given talc. Further evidence on the importance of fiber diameter was provided by Wagner et al (1976), who reported on rats injected intrapleurally with glass fiber (Table 11-3). Two samples of glass fiber were used, one with a median fiber diameter of 0.12 pm and the other with a median diameter of 1.8 pm. Four mesotheliomas were observed in 32 rats injected with the finer fiber and none with the coarser fiber. Also, the tyy degree of mesothelial cell hyperplasia was more pronounced in the rats injected with the finer fiber. the previous experiment. These results were comparable with those of 7*: ; ^ a. Shabad et al (1974) reported that when 20 mg of Russian,',. chrysotile was injected intrapleurally 3 times into 67 rats, 31 developed^ 5 mesotheliomas within 2 years. (b) Ingestion Gross et al (1974) reported the results of a series of feeding^.'/ experiments with chrysotile and crocidolite fed to rats of various origins. In groups of rats varying in number from 10 through 35, no significant differences in tumor incidence were observed in comparison with controls. Survival rates were not reported, sample sizes were small (from 10 through 35) and no pathologic details were given. In another experiment, Wagner et al (1976) fed 100 mg/day of talc (5 days/week) or chrysotile in malted milk powder for 100 days over a 6-month period to groups of 32 Wistar SPF rats; 16 controls were fed only malted milk. The mean survival from the start of feeding was 614 days for talc, 618 for chrysotile, and 641 days for the controls. The only tumors which may have been associated with ingestion were two gastric leiomyosarcomas; 7 GG I '_3j-2 I BB 0005195" on in an animal fed talc and the oth r in one fed chrysotile. None occurred in the controls. (c) Inhalation Lynch et al (1957) exposed AC/FI hybrid mice by inhalation to a commercial preparation of chrysotile asbestos and observed a higher Incidence of multiple pulmonary adenomas in the exposed group of animals, 45.72 (58/127), as compared with the 36.0% (80/222) in controls. results were reported as not statistically significant. These /"V Reeves et al (1974) exposed groups of 30 Swiss mice to dusts of crocldolite, amosite, and chrysotile for 4 hours/day, 4 days/week, for 2 years at a mean concentration of about 50 mg/m3. Two of the animals exposed to crocldolite developed papillary carcinomas of the bronchus, as did one of the nonexposed controls. * Olf -- (. Gross et al (1967) observed carcinomas of the lung in rats repeatedly exposed to chrysotile dust with a mean concentration of 86 mg/m3 for 30 hours/week. Twenty of 72 rats surviving for 16 months or longer developed adenocarcinomas and 4 developed squamous-cell carcinomas, whereas no tumors occurred in 39 controls. The authors suggested that the presence of trace metals from the hammers of the mill used to prepare the fiber was a factor in causing these tumors. However, this suggestion was not confirmed by subsequent experiments (Reeves et al, 1974; Wagner et al, 1974), thus leading Gross et al (1974) to retract the trace metal hypothesis for asbestos-induced neoplasia. Reeves et al (1971) found squamous carcinomas of the bronchus in 2 of 31 rats which survived exposure to crocidolite for 2 years at a concentration of 49 mg/m^ for 16 hours/week. Five rats in a group of 40 8 GG I -V&3 I BB 0005196 reduced to 75Z of the initial value (Evans et al, 1973). In early experiments, guinea pigs and monkeys exposed to the four commercial types'of asbestos developed fibrotic lesions of the lung and pleura similar to those seen in human cases of asbestosis (Vorvald et al, 1951; Wagner, 1963; Holt et al, 1965). In more recent experiments, this finding has been confirmed in rats (Wagner et al, 1973). The question whether asbestos fibers can move from their site of primary deposition in the body and induce cancer in other sites is still a vexing one. Volkheimer (1973) and Schreiber (1974) have reported that particles and plant fibers ingested by experimental animals and man can penetrate the wall of the gastrointestinal tract and be transported throughout the body, possibly appearing in the urine. Westlake et al (1965) fed a diet containing 6% of chrysotile to rats and reported that the animals had fibers in the wall of the colon. Cunningham and Pontefract (1973) performed a similar experiment and reported that asbestos fibers appeared in the blood and various tissues. A more recent report by Gross et al (1974) concluded, however, that there was no satisfactory evidence from their study of transmigration of fibers outside the gastrointestinal tract. In studies in which chrysotile labelled intrinsically with radioactive trace metals by neutron irradiation was injected intrapleurally into rats, Holmes and Morgan (1967) found evidence of where a small amount of the fiber passed from the pleural cavity and lungs into such other organs as the liver. In a later, similar experiment, Morgan et al (1971) reported that a population of radionuclides, consistent with that expected on the basis of the labelled chrysotile, was found in the heart, the lungs, q cn o 11 I BB 0005199 | -isV the diaphragm, and the chest muscles. Karacharova et al (1969) and Friedrichs et al (1970) found some evidence of movement of asbestos fibers from an ip site of injection into various tissues in rats. The latter group of investigators reported that movement was inversely related to the length of the fiber, becoming essentially zero for fibers 20 or more pa. long. Roe et al (1967) and Kanazawa et al (1970) found evidence of transport of asbestos fibers from subcutaneous sites of deposition to sucfi^ organs as the spleen, the liver, kidneys, and the brain of mice^, . "V' Cunningham and Pontefract (1973, 1974) reported that iv-injected asbestos t' localized mostly in the liver and the lungs. The later paper found further that chrysotile injected iv into pregnant rats crossed the placenta and. appeared in the livers and lungs of the fetuses. r Mutagenicity Sincock and Seabright ** (1975) found that chrysotile and crocidolitd'. asbestos dust in a concentration of 0.01 mg/ml in culture medium induced chromosomal aberrations in Chinese hamster cells. However, these changes were hot observed with glass fiber or glass powder. | B0 0005200 | 12 REFERENCES FOR CHAPTER II 1. Miller L, Smith WE, Berlinger SW (1965): Tests for effect of asbestos oi( benzo(a)pyrene carcinogenesis in the respiratory tract. Ann NY Acad Sci 132:489 2. Vosame A (1972): in International Agency for Research on Cancer, Annual Report 1971. Lyon, p 46 3. Pylev LN (1972): Morphological lesions in rat lungs induced by intratracheal injection of chrysotile asbestos alone and with;."benzo(a)pyrene. Vopr Onkol 18:40 4. Pylev LN, Shabad LM (1973): Some results of experimental studies in asbestos carcinogenesis, in Bogovski P, Gilson JC, Timbrell V, Wagner JC (eds): Proceedings of the Conference on Biological Effects of Asbestos. Lyon, 99 pp 5. Shabad LM, Pylev LN, Krivosheeva LV, Kulagina TF, Nemenko BA (1974):ZZp Experimental studies on asbestos carcinogenicity. J Natl Cancer Instj^ ^ 52:1175 6. Reeves AL, Puro HE, Smith RG, Vorwald AJ (1971): Experimental asbestos carcinogenesis. Environ Res 4:496 7. Maltoni C, Annoscia C (1973): Mesotheliomas in rats following the intraperitoneal injection of crocidolite, in Maltoni C, Davis W (eds): Characterization of Human Tumors. Proceedings of the Fifth International Symposium on the Biological Characterization of Human Tumors. Bologna. 4-6 April 1973, Veil, 115 pp 8. Pott F, Friedrichs KH (1972): Tumoren der Ratten Nach I. P. Injektion faser formiger Staube. Naturwissenschaften 59:318 9. Pott F, Huth F, Friedrichs KH (1974) Tumorigenic effect of Fibrous Dusts in Experimental Animals. Environ Health Pers 9: 10. Pott EF, Huth F, Friedrichs KH (1972) : Rat tumors after intraperitoneal injection of ground chrysotile asbestos and benzo(a)pyrene zentralblatt fur bakteriologic, Parasitenkunde, Infelitionskrankheiter und Hygiene I Abt Orig, Reihe B, vol 155, no 5-6, pp 463-69 11. Wagner JC, Berry G, Timbrell V (1973): Mesotheliomata in rats after inoculation with asbestos and other materials. Br J Cancer 28:173 12. Stanton MF, Wrench C (1972): Mechanisms of mesothelioma induction with asbestos and fibrous glass. J Natl Cancer Inst 48: 797 13 j BB 000520 I^J, Stanton MF (1973): Some aetiological considerations of fibre carcinogenesis, in Bogovski P, Gilson JC, Timbrell V, Wagner JC (eds): Proceedings of the Conference on Biological Effects of Asbestos.^ Lyon, 284 pp Donna A (1970): Tumori sperimentali da amianto di crisotilo, crocidolite e amosite in ratto Sprague-Dawley. Med Lav 61:1 Smith WE, Miller L, Elsasser RE, Hubert DD (1965): Tests for carcinogenicity of asbestos. Ann NY Acad Sci 132:456 Groth DH, Stokinger HE, Phipps FC, Conner WL (1975) : Carcinogenic Activity of Asbestos Coated with 3-4-Benzo-a-pyrene. Oral presentation at the AIHA meeting in Minneapolis, Minnesota, 5 June Wagner JC, Berry G (1969): Mesotheliomas in rats following^^ r _ inoculation with asbestos. Br J Cancer 23:567 .V? Harrington JS (1962): Occurrence of oils containing 3:4-benzopyrene-- and related substance in asbestos. Nature (London) 193:43 I Harrington JS, Roe FJC (1965): fibres and their natural oils. Studies of carcinogenesis of asbestos^ Ann NY Acad Sci 132:439 c Roe RJC, Walters MA, Harrington JS (1966): Tumor initiation by*L natural and contaminating asbestos oils. Int J Cancer 1:491 ' > Commins BT, Gibbs GW (1969): Contaminating organic material in~~' asbestos. Br J Cancer 23:358 PH "L-7 Morgan A, Holmes A (1970): ,\ ' C.3 Neutron activation techniques in{^| investigations of the composition and biological effects of asbestos,-j ^ in Shapiro HA (ed): Pneumoconiosis. Proceedings of the^y International Conference, Johannesburg. Cape Town, Oxford University Press, p 52 Morgan A, Holmes A, Gold C (1971): Studies of the solubility of constituents of chrysotile asbestos in vivo using radioactive tracer techniques. Environ Res 4:558 Kanazawa K, Birbeck MSC, Carter RL, Roe FJC (1970): Migration of asbestos fibres from subcutaneous injection sites in mice. Br J Cancer 24:96 Timbrell V, Rendall REG (1972): Preparation of the UICC standard reference samples of asbestos. Powder Technol 5:279 Occella E, Maddalon G (1963): X-ray diffraction characteristics of some types of asbestos in relation to different techniques of comminution. Med J Lav 54:628 14 I BB 0005202 | 27. Wagner JC, Berry Gf Cooke TJ, Hill RJ, Pooley FD, Skidmore JW (1976): Animal experiments with talc. Fourth International Symposium on Inhaled Particles and Vapors, Edinburgh, September 1975 (In press) 28. Wagner JC, Berry G, Skidmore JW (1975a): Studies of the carcinogenic effect of fibre glass of different diameters following intrapleural inoculation in experimental animals. NIOSH Symposium on Occupational Exposure to Fibrous Glass, University of Maryland, June 1974, HEW publication No. (NIOSH) 76-151. Dept of Health, Education, and Welfare, Public Health Service, Center for Disease Control, NIOSH, April 1976, pp 193-197 29. Gross P, Harley A, Swinburne LM, Davis JMG, Greene WB (1974): Ingested mineral fibers. Do they penetrate tissue or cause cancer? Arch Environ Health 29:341 30. Lynch KM, Mclver FA, Cain JR (1957): Pulmonary tumours in mice exposed to asbestos dust. Arch Ind Health 15:207 C/5 q jy 31. Reeves AL, Puro HE, Smith RG (1974): Inhalation carcinogenesis from ^ various forms of asbestos. Environ Res 8:178 *"*- n 'p 32. Gross P, deTreville RTP, Tolker B, Kaschak M, Babyak MA (1967): Experimental asbestosis. The development of lung cancer in rats with pulmonary deposits of chrysotile asbestos dust. Arch Environ Health c . ^ 15:345 '> 33. Wagner JC, Berry G, Skidmore JW, Timbrell V (1974) : The effect of f the inhalation of asbestos in rats. Br J Cancer 29:252 34. Timbrell V (1965): The inhalation of fibrous dusts. Ann NY Acad Sci, 132:255 "J 35. Timbrell V (1972): Inhalation and biological effects of asbestos, in^S Mercer TT, Morrow PE, Stober W (eds): Assessment of Airborne Particles. Proceedings of the Third Rochester International Conference on Environmental Toxicity, Rochester, Springfield, 111., Thomas, p 429 36. Langer AM, Pooley FD (1973) : Identification of single asbestos fibres in human tissues, in Bogovski P, Gilson JC, Wagner JC (eds): Proceedings of the Conference on Biological Effects of Asbestos, Lyon, p 119 37. Evans JC, Evans RJ, Holmes A, Hounam RF, Jones DM, Morgan A, Walsh M (1973): Studies on the deposition of inhaled fibrous material in the respiratory tract of the rat and its subsequent clearance using radioactive tracer techniques - I. UICC crocidolite asbestos. Environ Res 6:180-201 15 j BB 0005203_| 38. Vorwald AJ, Durkan TN, Pratt PC (1951): Experimental studies of asbestosis. Arch Ind Hyg 3:1 ,,39. Wagner JC (1963): Asbestosis in experimental animals. Br J Ind Med 20:1 r 40. Holt PF, Mills J, Young DK (1965): Experimental asbestosis with four types of fibers: Importance of small particles. Ann NY Acad Sci 132:87 41. Sincock A, Seabright M (1975): Induction of chromosome changes in Chinese hamster cells by exposure to asbestos fibres. Nature 257:56 42. Volkhelmer G (1973): Persorption. Acta Hepato-Gastroenterol 20:361 43. Schreiber G (1974): Ingested dyed cellulose in the blood and urine of man. Arch Environ Health 29:39-42 /!) UiJ 44. Westlake GE, Spjict HJ, Smith MN (1965): Penetration of coloniET mucosa by asbestos particles. Lab Invest 14:2029-33 ^ -Z. ^ 45. Cunningham HM, Pontefract RD (1973): Asbestos In beverages, drinking 1 water and tissues: their passage through the intestinal wall and movement through the body. J Assoc Agric Chem 56:976-81 46. Holmes A, Morgan A (1967): Leaching of constituents of chrysotile asbestos in vivo. Nature 215:441-42 47. Karacharova VN, Ol'Shavang RA, Kogan FM (1969): Changes in certain organs after experimental intraperitoneal injection of asbestoscontaining dust. Byull Eksp Biol Med 67:117-120 48. Friedrichs KH, Hilscher W, Setki S (1971): Fiber and tissue studies on rats after Introperitoneal injection of asbestos. Arch Arbeitsmei--28:341-54 49. Roe FJC, Cartes RL, Walters MA, Harrington JS (1967): The pathological effects of subcutaneous injections of asbestos fibers in mice: Migration of fibers to submesothelial tissues and induction of mesotheliomata. Int J Cancer 2:628-38 50. Cunningham HM, Pontefract RD (1974): Placental transfer of asbestos. Nature 249:177-78 (J, i--3' 16 ["bb"0005204_J m SUMMARY TABLE OF ASBESTOS-INDUCED CARCINOGENICITY IN ANIMALS Author Date Finding Type of AnInal Doaaga Type of FIbar INTRATRACHEAL IHSTILLATIOH Hiller Vosanae Pylev Pylev 6 Shabad Shabad et al 1965 1972 1972 1973 1974 Tumore of respiratory tract Hamster It Riti H II it Lung papillomas, epidermoid carcinomas retlculosarcomae, pleural meaotbeliomaa 6/21 and 6/11 rets within 9-28 non n Unknown 19 'i. Chryaotlle with banco (a) pyrene If If 2 ng Hubslan chryaotlle S ng banco (a) pyrene Russian chryaotlle 1HTRAPERIT0HEAL ADHIHISTRATIOH Reeves et al 1971 3/13 peritoneal mesotheliomas with chryaotlle 3/13 peritoneal mesotheliomas with croclodolite 0/11 peritoneal mesotheliomas with anoslte After 7-17 non 0.3, 0.3 or 1.0 ad of solution of 20 ng/nl. Anoslte Crocidolite Chryaotlle Halton1 I 1 Cl O Potta and Frledrlcha BB 0005205 "I c_o Pott C_- ' ro 1 1973 1972 1974 31/30 neaothellosui In sale* 34/30 mesothelioma In females Sprague-Dawley rate <18 wk old) 402 tumor occurrence Wletar rate nM T 01D ii HLS 23 mg cro cidolite 2, 6.23, 23, 73, 100 mg 2, 10, 50 mg Crocidolite Chryaotlle A H l m 00 u\ \ \s\ \s\ 0'\ U' SUMMARY TABLE OF ASBESTOS-INDUCED CARCINOGENICITY IN ANIMALS (CONTINUED) Author INTRAPLEURAL ADMINISTRATION Wagner Stanton and Wrench Pylev and Shabad Croth et al Wagner Reeves at al Reevea et al Shabad et al CD vT~> C.O OJ Data Rinding Type of Animal Dosage Type of Fiber 1973 1972 61X tumors with crocidollte Rata 361 tuaors with aaoalte 361 tuaors with anthophylllta 30X tunora with Canadian chrysotlle 19X tunora with Rhodesian chrysotila Haaothalloaaa in 60X rata H 1973 Heaothalloaaa 1* 1975 1976 1971 1971 1974 No aasothelioaas-but animala killed 90-150 d after inject Ion-Insufficient latent period Albino rats 18/40 meeothellomas0/48 aesothelioaaa-talc 1/15 aeaothelloaa with crocidollte 2/12 akeaothelloaa with chrysotila Rata II 2/13 aeaothelloaa with chrysotila Rabbit 31/67 aeeothelloaas within 2 7r Rata 0 6 t M| L US,4J 1i i ^vs i i 20 mg 40 ag 60 ag Unknown CTocldolite Amoslte Anthophylllta Canadian chrysotlle Rhodesian chrysotlle Crocidollte Aaoalte and Rhodesian cbryaotila Ruaalah chrysotila .5 al .8 al 20 ag Chrysotlle Talc Aaoalte Crocidollte Chryeotlle Chrysotila Russian chrysotila SUMMARY TABLE OF ASBESTOS-INDUCED CARCINOGENICITY IN ANIMALS (CONTINUED) Author INGESTION Gross ct si Wagner et ml INHALATION Lynch et al M3 Reeves et al Gross et al C") Reeves et al C~) CO t Data Finding Type of AnInal Dosage Type of Fiber 1974 1976 Ho significant difference in tuaor incidence observed survival rates not reported eaaple sites were aaall Rats 2 gastric leiomyosarcomas, 1 in antes1 fed talc and 1 fed chryeotile 32 Wlatar SPF rata 5X fiber by weight in food 100 ag/d/ 5 d/wk 100 d over a 6-aon period Chrysotlle and Crocidollte Chrysotlle r Talc 1957 45.7 (58/127) pulmonary adenoaas in exposed group 36.02 (80/222) pulmonary adenoaas In controla AC/F hybrid nice 1974 2/30 bronchiogenic carci noma with chryeotile Swiss nice 1967 1971 l/. . 1. 20/72 rats surviving 16 non or longer developed adeno-carclnoaas 4/72 rata developed squaaoue-cell carcinomas 0/39 tuaore in controls 2/31 rata developed carcinoma of the bronchus with crocidollte exposure 5/40 rats developed adenoaatosle with chrysotlle exposure Rats 19 'm ; _ ( ' ' -\ t ..US ; :.5L.O Dust concen Chrysotlle trations ranged from 150.000.000 to 300.000.000 particles per cc. 50 ag/a? 4 hr/d, 4 d/wk for 2 yr Crocidollte Aaoalte Chrysotlle 86 ag/a3 for 30 hr/wk Chrysotlle dust 49 ag/a? for 16 hr/wk for 2 yr Crocidollte Chrysotlle Aaoalte SUMMARY TABLE OF ASBESTOS-INDUCED CARCINOGENICITY IN ANIMALS (CONTINUED) Author IHHALATIOH Wagner et el Slncock and Seabrlght hOo rinding Type of Animal Dosage Type of Fiber Asbeatoala produced with all type* of fibers C/D Ulster rate Lung Cancer Mesothelioma Fiber 11/146 16/145 16/141 17/137 30/144 1/146 2/145 4/141 4/137 0/144 anoslte anthophylllte crocldollte chrysotlle (Canadian) chrysotlle (ShodesIan) Chromoeal abberatlon In Chinese hiwater cells Hamster 12 mg dust Chrysotlle hr/d -- Amosite d/wk for several lengths of exposure (1 d, 3 mon, 12 son, 24 mon) 0.01 mg/ml Chrysotlle Crocldollte i ;- v. - TABLE XI-1 TUMORS IN ABDOMEN AND/OR THORAX AFTER INTRAPERITONEAL INJECTION OF DIFFERENT FIBROUS AND GRANULAR DUSTS Dust Form* Dose i.p. (mg) Effective Number of Dissected Rats First Tumor After ... Days Average Survival Time of Rats with Tumors (days after inj.) Rats with Tumor (X) Chrysotile A UICC II It II If " milled Palygorscite Glass fibers S + S 106 If II Gypsum Nemalite Actinolite Biotite Haematite (precipit.) Haematite (mineral) Pectol'ite Sanidine Talc NaCl-Control f2 f 6.25 f 25 f 4 x 25 f 3 x 25 f 4 x 25 f 3 x 25 f2 f 10 f 4 x 25 f 4 x 25 f 4 x 25 g 4 x 25 g 4 x 25 g 4 x 25 g 4 x 25 g 4 x 25 g 4 x 25 g 4 x 25 4 x 2m *f fibrous g granular From Potts and Friedrichs (1972) 37 35 31 33 33 37 34 34 36 32 35 34 39 37 34 38 40 39 36 72 431 343 276 323 449 400 257 692 350 197 579 249 * -- -- " 569 579 587 - 651 501 419 361 449 509 348 692 530 325 583 315 -- " 569 579 587 - 16.2 77.1 80.6 54.5 3.0 32.4 76.5 2.9 11.1 71.9 5.7 73.5 -- -- 2.5 2.6 2.8 - NOTE: THIS DOCUMENT DID NOT COME FROM PPG FILES vis 21 I BB 0005209_| 6 TABLE II-2 TUMORS IN ABDOMEN AND/OR THORAX AFTER INTRAPERITONEAL INJECTION OF GLASS FIBERS, CROCIDOLITE AND CORUNDUM Dust Form* Dose l.p. (mg) Effective Number of Dissected Rats First Tumor After ... Days Average Survival Time of Rats with Tumors (days after inj.) Rats with Tumor (%) Glass fibers MN 104 It 11 Glass fibers MN 112 Crocldolite Corundum f f f f f g *f * fibrous g - granular From Pott et al (1974) 2 10 2 x 25 20 2 2 x 25 73 421 77 210 77 194 37 390 39 452 37 545 NOTE' NOT VjU'*45 " 703 632 367 615 761 799 27.4 53.2 71.4 37.8 38.5 8.1 * l- Bb"0O05210_^ 22 TABLE II-3 PERCENTAGE OF RATS DEVELOPING MESOTHELIOMAS AFTER INTRAPLEURAL INOCULATION OF VARIOUS MATERIALS / Material Percentage of rats with mesotheli mas SFA Chrysotile UICC crocidolite UICC amosite UICC anthopyllite UICC chrysotile (Canadian) UICC chrysotile (Rhodesian) Fine Glass Fibre (code 100) Ceramic fibre Glass powder Coarse glass fiber (code 110) 66 61 36 34 30 19 12 10 3 0 From Wagner et al (1976) NOTE: THIS DOCUMENT DID NOT COsViE FROM PPG FILES TABLE II-4 INHALATION CARCINOGENESIS FROM VARIOUS FORMS OF ASBESTOS Form of Asbestos Controls Amosite Crocidolite Crysotile From Reeves et al (1974) Number of Tumors no tumors 2 pleural mesotheliomas 3 squamous-cell carcinoma, 1 papillary carcinoma and 1 adenocarcinoma, all of lungs. 1 papillary carcinoma, 1 squamous-cell carcinoma of lungs, and 1 pleural mesothelioma. 23 \ TABLE II-5 NUMBER OF ANIMALS WITH LUNG TUMORS OR MESOTHELIOMA ACCORDING TO TYPE OF ASBESTOS Dust No. of Animals Adenocarcinoma Tumor Type Sq. Carcinoma Mesotheliomas Controls Amosite Anthopyllite Crocidolite Chrysotile (Canadian) Chrysotile (Rhodesian) 126 146 145 141 137 144 From Wagner et al (1974) 0 00 5 61 8 82 7 94 11 6 4 19 11 0 MOTE: TH'T DOCUMENT DIO ft'S F114S TABLE II-6 NUMBER OF ANIMALS WITH LUNG TUMORS OR MESOTHELIOMA ACCORDING TO LENGTH OF EXPOSURE Length of Exposure No. of Animals No. with Lung CA Controls 1d 3 mon 6 mon 12 mon 24 mon 126 219 180 90 129 95 From Wagner et al (1974) 0 3 8 7 35 37 No. with Pleural Mesotheliomas 0 2 1 0 6 2 % of Animals with Tumors 0.0 2.3 5.0 7.8 31.8 41.0 24 OOO^ll- \ Effects of Inhalation of Asbestos in Rats Weight of dust in lungs (mg) 0 10000 20000 30000 Cumulative dose (mg/m3 hours) Mean weight of dust in lungs of rats in relation to dose and time, from Wagner et al (197M FIGURE IT-1 25 V III. EFFECTS ON HUMANS Nonmalignant Respiratory Diseases (a) Historical Studies NOTE: THIS DOCUMEMT OiO not cosViE mm ??q files The use of asbestos dates back thousands of years; however, the modern industry dates from about 1880, when it was used to make heat and acid resistant fabrics, (Hendry, 1965; Hueper, 1966). With the increasing use of asbestos materials, reports of asbestos-related disease emerged. The first record of a case of asbestosis was reported in England by Montague Murray in 1906. Hoffman (1918) reported that it was the practice of American and Canadian insurance companies not to insure asbestos workers due to unhealthful conditions in that industry. Pancoast et al (1917) commented on x-ray changes resembling pneumoconiosis in 15 individuals exposed to asbestos. The first complete description of asbestosis and of the "curious bodies" seen in lung tissue appeared when Cooke (1927) reported on a case of asbestosis, and McDonald (1927) reported on the same and another case. Each author gave reasons for believing that these "curious bodies" originated from asbestos fibers that had reached the lungs. Mills (1930) reported the first case of asbestosis in the United States, and in the same year. Lynch and Smith (1930) reported on "asbestosis bodies"* found in the sputum of asbestos workers. Early studies led many investigators to conclude that people exposed to asbestos *"Ferruginous bodies" is a more descriptive term, as other inhaled fibers, eg, fibrous glass, may also become iron coated. GO I'-*' "["bT 00 0522^.1 dust developed the disease "asbestosls" If the dust concentration was high or their exposure was long (Merewether and Price, 1930; Merewether, 1934; Fulton et al 1935; Dreessen et al, 1938) j v (b) Epidemiologic Studies NOT COME FROM PPG FILES Harries (1968) reported that although first impressions would lead one to believe that only workers continuously exposed to asbestos are at risk of developing asbestosls, further consideration of the industry and processes should have suggested that many other workers were also at risk. For example, some trades worked in confined spaces where asbestos was used. Work in shipboard trades was accepted by the Pneumoconiosis Panel of the United Kingdom as associated with asbestosls. Murphy et al (1971a) found that asbestosis was 11 times more common among pipe insulators involved in new ship construction than among a control group. Asbestosis first appeared 13 years after exposure or at about 60 mppcf-years. The prevalence was 38% after 20 years. They also reported a case of extensive pleural calcification in a worker whose only known asbestos exposure was during sanding asphalt and vinyl tile floors (Murphy et al, 1971b). Lorimer et al (1976), in a study of brake repair and maintenance workers exposed to asbestos, found that 25% of the workers showed evidence of x-ray abnormalities consistent with asbestosis. One quarter also had restrictive pulmonary function test findings. Meurman et al (1973) found a three-fold risk of dyspnea and a two fold risk of cough for asbestos workers as compared with controls, after adjusting for smoking. Weill et al (1975) reported a decreased lung function in relation to 27 i'BB 00Q5215_^ Increasing cumulative dust exposure in a group of asbestos cement manufacturing workers. Ayer and Burg (1976) reported a decrease in pulmonary function in asbestos textile workers with less than ten years of exposure. ' NOTE: THIS DOCUMENT m PfiflLSIn a study of 232 former insulation pEiilibfllf reported positive x-ray findings among individuals having exposures to asbestos known to be as short as 1 day. More recently, Anderson et al (1976) reported x-ray findings consistent with asbestosis in household and family members having no known exposure to asbestos other than residing with a known asbestos worker. These two studies demonstrate the presence ' of asbestos disease in the absence of continuing new known exposures. Wagoner et al (1973) demonstrated a significantly increased risk of death from nonmalignant respiratory disease and for diseases of the heart, which in part were secondary to pulmonary disease, among a cohort of workers in a major manufacturing complex using predominately chrysotile. Among those workers observed 20 or more years after onset of employment, a four-fold Increased risk of death due to nonmalignant respiratory disease was observed. Further evaluation of these deaths revealed that the majority occurred within 1 year after termination of employment and at an average age of 53.8 years. Newhouse (1969) reported an increased risk of death from nonmalignant respiratory disease in male asbestos textile and insulation workers with low to moderate exposure. Enterline and Henderson (1973) reported that for all ages, only 18 deaths from asbestosis occurred in several asbestos plants studied from 1941 to 1969. It is significant to note, however, that the state of New GG 1-343 28 I ob 00052^16 1 Jersey alone. In the yeaxs 1969-1970, had awarded workman's compensation for asbestosis to 455' workers from one of (Heymann, 1971; Serrainc^ 1970) Selikoff (1976a) ^reported a significant excess of deaths due to asbestosis among a groups of workers in the US and Canada. Out of 17,800 . i asbestos insulation wjjjekers, there were 119 observed deaths attributed to asbestosis. Although itrewas not reported, the expected death rates from asbestosis in the gener^ population would be virtually zero. 6c) Descriptio^gof Asbestosis Asbestosis is a^chronic lung disease due to the inhalation of asbestos fibers and is characterized by diffuse interstitial fibrosis, frequently associated jwith pleural fibrosis (thickening) or pleural calcification. D, The characteristic- x-ray changes of asbestosis are small irregular opacities in the lower a^d middle lung fields, often accompanied by pleural thickening and pleural calcifications. The pulmonary fi^rotic changes develop slowly over the years--often progressively even without further exposure--and their radiographic detection is a direct^ correlate of their extent and profusion. In some cases, minor fibrosis with considerable respiratory impairment and disability can be present without equivalent x-ray changes. Conversely, extensive radiographic findings may be present with little functional impairment. t Commonly found In asbestosis are pulmonary rales, dyspnea, finger er clubbing and cyanosis, but any or all can be absent in any one case. " ,,& Pulmonary hypertension is frequently associated with advanced tt DID 29 asbestoais and the resultant cor pulmonale (right-sided heart failure) may be the cause of death. Carcinogenicity (a) Occupational Exposure NO" CO* IS (1) Historical Studies V .......... iVu .-.Ltd In 1935, 55 years after the start of large-scale usage of asbestos in industry, suspicion of an association between asbestosis and lung cancer was reported by Lynch and Smith (1935) in the USA and by Gloyne (1935) in the UK. About 10 years later, case reports of pleural and peritoneal tumors associated with asbestos appeared (Wedler, 1943, a,b; Wyers, 1946). Epidemiologic evidence from Doll (1955) showed a ten-fold excess risk of lung cancers in those UK asbestos textile workers who had been employed before 1930, before regulations produced improved dust conditions in factories. Similar findings were reported in the USA in 1961. Mesotheliomas were also detected but this fact was not published until later (Mancuso and Coulter, 1963; Selikoff et al, 1964). Possible variations in risk with different types of fiber were rarely considered in the early reports. Since 1964, following the recommendations of the UICC Working Group on Asbestos Cancers (UICC 1965) for new studies, there has been an expansion of epidemiologic studies in many parts of the world. (2) Epidemiologic Studies (A) Lung Cancer, Pleural and Peritoneal Mesotheliomas (i) Mixed Types of Fiber In most industrial processes different types of fiber are mixed, so that pure exposures to a single asbestos type are rare. Mortality studies of defined peculations of asbestos-manufacturing, 3C | QB 0005213 | w Insulating, and shipyard workers have provided the most concrete evidence concerning the association between bronchial cancer, pleural, and peritoneal mesotheliomas and exposure to asbestos. Reports have come from CO LU several countries: (UK) Newhouse, 1969; (FRG) Bohlig et al, 1970; (USA) Q Selikoff et al, 1970; (UK) Elmes and Simpson 1971; (The Netherlands) Stumphius, 1971; (Italy) Rubino et al, 1972. v A seven-fold excess of lung cancer was found in a group of insulation workers whose exposures had been to chrysotile and GO amosite but not crocidolite (Selikoff et al, 1971). Enterline and Henderson (1973) reported a 4.4 times increased risk of respiratory cancer mortality among retired men who had worked as production or maintenance employees in the asbestos industry and who had been exposed to mixed fibers. Among men with mixed exposure to crocidolite and chrysotile in the asbestos cement industry, the rate was 6.1 times the expected rate. In a British naval dockyard population, Harries (1976) showed that there had been a steep rise in mesotheliomas since 1964. However, the full biologic effects of asbestos in shipyard workers would not have been expected to be detected until the 1970's and thereafter (Selikoff, 1976a). Edge (1976) reported that shipyard workers with mixed asbestos exposure and pleural plaques (without evidence of pulmonary fibrosis) had a 2.5 times increased risk of developing carcinoma of the bronchus, when compared with matched controls without plaques. In a study of sheet metal workers (Cooper et al, 1975) with measurable and mixed asbestos exposure, an excess of deaths from malignant neoplasms (24.7* of deaths for two cohorts selected for 5 or more years worked in the trade, 19.1Z of deaths for a group with death claims where 14.5Z was expected) was 31 C-G 1134- j rr 0005219 largely attributed to an excess of malignant tumors of the respiratory tract. Of the 307 deaths In the first cohort, 32 lung cancer deaths were significantly In excess (1. was observed. association between mesotheliomas and past exposure to asbestos comes from many institutes and departments of pathology and cancer registers, eg, (France) DeLarjarte et al, 1973; (Italy) Gobbato and Ferri, 1973; (South Africa) Webster, 1973; (UK) Greenberg and Lloyd Davies 1974; (FRG) Hain et al, 1974; (Finland) Nurminen and Markku), (German Democratic Republic) Sturm, 1975; (The Netherlands) Zlelhuls et al, 1975). These studies have shown an association between asbestos and mesothelioma even with exposures as brief as 1 day; however, approximately 152 of the mesotheliomas are not known to be related to exposure to asbestos. Three studies (McDonald et al, 1973; Greenberg and Lloyd Davies, 1974; Newhouse et al, 1972) showed a poor correlation between certified cause of death and histologic diagnosis of mesothelioma. There is still a need to reduce the inter-observer variation in the diagnosis of these rare and pleomorphic tumors (McCaughey and Oldham, 1973). The ratio of pleural to peritoneal tumors appear to be associated with heavier exposures (Newhouse et al, 1973). Among a number of occupationally exposed groups studied, approximately 5 - 72 of deaths have been from mesotheliomas (Gilson, 1973; Hammond and Selikoff, 1973; Selikoff, 1976b). More recently however, an estimate has projected that 112 of asbestos workers' deaths in England will be from mesotheliomas (Newhouse and Berry, 1975). (ii) Individual Types of Fibers Crocidolite In 1956, Wagner started investigating the occurrence of pleural and peritoneal mesotheliomas In the crocidolite mining areas of the Northwest Cape Province in South Africa. It was shown that these tumors occurred in the nonmining population living in the vicinity as well as among men working in the mines and mills and In the transportation and handling of the fiber (Wagner, 1960). Asbestosis was not invariably present. The latent period between first exposure and clinical recognition of the tumor was long - a mean of 40 years. Subsequent surveillance of the mining population in all the asbestos- producing areas In South Africa has added support for a major difference in the incidence of mesotheliomas within the crocidolite mining areas of that country. (Harrington et al, 1971; Webster, 1973). The mining of crocidolite In northwest Australia has been associated with mesotheliomas (McNulty 1962). Jones et al (1976) have reported a high incidence of mesotheliomas among women who worked with crocidolite in a factory producing gas mask canisters during World War II. Chrysotile McDonald et al (1973, 1974) reported that the overall death rate among 11,500 workers born between 1891 and 1920 and employed in the chrysotile mines and mills of Quebec was lower than for Quebec Province as a whole. An increased lung cancer risk was found and considered to be dose-related, and those who had been most heavily exposed to the dust showed about a five-fold risk compared with the least exposed. Of the 3,270 deaths, 134 were from respiratory cancer, with 129 being lung cancer and 5 mesotheliomas. Recently, the authors (McDonald 33 |-SB- 0005221 1 and McDonald, 1976) have observed 3,938 total deatha among males through 1973, of which 224 were from lung cancer and 7 from mesothelioma. The authors suggested that the respiratory cancer mortality In the Quebec chrysotile industry as a whole was greater l^aa-that" expected) bn ' HeT "hasfa 1 f) of regional mortality data. Kogan et al (1972) investigated the cancer mortality among workers In asbestos mining and milling industries between 1948 and 1967. The total cancer mortality rate among workers was 1.6 times higher than that found In the general male population; for female workers the rates were 0.8 for those in mines and 1.3 for those In mills. The lung cancer risk for male miners and millers was twice that of the general male population. For females In mines and mills, the risks were 2.1 and 1.4 times that of the general female population, respectively. For those workers over 50 years of age, the risk of lung cancer was greater: for men in mining, 4.9; those in milling, 5.9; for women in mining, 9.5; and for those women in milling, 39.8 times that found in the general population. No mesotheliomas were found, but Kogan et al (1972) indicate that this might be explained by the insufficient experience of pathologists with this rare type of cancer in that geographical area. Also, the number of people in the study populations were not reported. Vagoner et al (1973) reported on the cancer risk among a cohort of workers in a major manufacturing complex utilizing predominately chrysotile asbestos in textile, friction, and packaging products. An excess of respiratory cancer occurred among asbestos workers in each duration-of-employment category down to and including 1-9 years. They observed statistically significant standard mortality ratios of 122 34 j BB 00052221 for all malignant neoplasms and 244 for malignant neoplasms of the respiratory system. The asbestos workers In this study were located In an area of predominately Amish Dutch population with known low frequencies of smoking. The authors, nevertheless, used the general white male US population as a control group, which would tend to undergot;im^t the, degreei-j* rjin MOsEi j-': .. * wu of risk* - ',1 COQ r 13 Enterline and Henderson (1973) found that for retired men who had worked as production or maintenance employees in the asbestos industry and who had reached 65 years of age, those who had been exposed only to chrysotile had a respiratory cancer risk two - four times than that expected. Among men within the asbestos cement industry exposed only to chrysotile, a one- to four-fold excess of respiratory cancer was found. Of 802 deaths, only one mesothelioma had been recorded in the several plants investigated. In contrast, a subsequent investigation by Borow et al (1973) found 70 cases of mesothelioma from only one of these plants. The discrepancy was due to methodologic variations, for example. Enterline and Henderson (1973) had limited their investigation to men age 65 or over, while many of the mesothelioma cases reported by Borow et al (1973) had died before that age. Amosite In a study of a group of miners exposed to amphibole fibers in the cummingtonite-grunerite ore series, Gillman et al (1976) demonstrated mortality from malignant respiratory disease to be three times than that found in the general population. Exposures to amosite alone in a factory making Insulation material were reported by Selikoff (1976 a & b). Ten mesotheliomas were found in addition to an increased risk of lung cancer in 35 GG l-.35n + BB QQQ5??1 I C /J workers who were observed 20 years or longer. The excess lung cancer risk In the amoslte workers was shown to Increase with duration of employment. There was a tshree-fold increase in lung cancer among those with less than 3 months employment and among those with was a 2.25-fold increase. In a retrospective study of 914 men who had worked periodically during World War II in a plant manufacturing insulating materials from amoslte for the US Navy, Seidman et al (1976) concluded that the group of 65 men who had worked for less than 1 month had experienced excess mortality, on the age-specific basis, from lung cancer during the 30 years since the beginning of their exposure, but not from all cancers or all causes of death. Men who had worked for a full month or longer had excess mortalities from all three causations examined, the risk of death from lung cancer increasing with duration of exposure. Anthophyllite - In Finland, anthophyllite mining has been associated with an excess bronchial cancer risk of 1 - 4 times the expectation overall, and about double this figure for those with more than 10 years' exposure (Meurman et al, 1974). There was also a higher prevalence of dyspnea and cough in the miners. However, no mesotheliomas were found despite the presence in Finland of an unusually high incidence of pleural thickening and calcification as detected by radiographic and pathologic surveys (Kiviluoto, 1960; Meurman, 1966). (B) Other Types jf Cancer Epidemiologic studies of the already defined populations have consistently shown n excess risk of other cancers. 36 | BB 0005224 especially of the gastrointestinal tract (Mancuso and El Attar, 1967; Elmes and Simpson, 1971; Kogan et al, 1972; Newhouse, 1973; Wagoner et al, 1973; McDonald et al, 1974; Selikoff et al, 1974); ho1 that of lung cancers. emphasis on dose-response, concluded that "good dose-response data, with quantitative estimates of dose are uncommon; however, in all the literature reviewed, only one paper did not support the conclusion that increased exposure to inhaled asbestos particles leads to increased digestive system cancer." Stell and McGill (1973) found that out of 100 men with squamous carcinoma of the larynx, 31 had known exposure to asbestos compared with only three in matched controls. Similar associations have been reported by Morgan and Shettigara (1976). Newhouse and Berry (1973) found two cases of cancer of the larynx (ICD 161) in their cohort of over 4,000 workers compared with an expected 0.4. (b) Nonoccupational Exposure Household contact with asbestos is associated with an increased mesothelioma risk. Anderson et al (1976) have recently reviewed 34 such cases of mesothelioma from nine countries and reported four new cases among the traced family members of 1,664 asbestos workers. Cases of mesotheliomas have also occurred in nonoccupationally exposed individuals living in the neighborhood of industrial sources of asbestos (Wagner et al, 1960; Newhouse and Thompson, 1966; Bohlig and Hain, 1973). Studies of the geographical distribution of cases of mesothelioma in the UK over a 10-year period indicate that the new cases are nearly all from areas in which there | BB 0005225 37 GO '"30Z has been a recognized Industrial source of asbestos (Gilson, 1970; Greenberg and Lloyd Davies, 1974). Lesions aipong nonoccupatlonally exposed persons in Finland have been reported where anthophyllite asbestos is mined. In this study, 118 cases of the total 126 cases of roentgenologically-diagnosed pleural calcification studied, excluding those individuals with hemothorax, emphysema, and tuberculosis, lived or have lived in areas immediately adjacent to asbestos mines (Kiviluoto 1960). The results of this study suggest a health hazard from community exposur SYNERGISM There is marked enhancement of the risk of lung carcinoma in those workers exposed to asbestos who also smoke cigarettes (Sellkoff et al, 1968; Doll, 1971; Berry et al, 1972; Hammond and Selikoff, 1973); Hammond and Selikoff (1973) interpret the excess lung carcinoma risk from asbestos in nonsmokers to be small. No link between cigarette smoking and mesotheliomas has been observed in a prospective study by Hammond and Selikoff (1973). A preliminary study (Lemen, 1976) on female workers employed between January 1940 and December 1967, in a predominately chrysotile asbestos textile plant, revealed 7 lung cancer deaths among 580 women when only 0.63 deaths were expected (p<0.01). One lung cancer death was observed in a smoker, two in women of undetermined smoking history, and four in "never" smokers as determined from hospital admission charts. It is important to note that the historic documentation of cigarette consumption patterns is lacking for most retrospective cohort studies of asbestos workers. It is further important to note that a sizable portion of the general population, the group us', lly selected for comparison in 38 rBB'0Q0S226j these studies, are cigarette smokers. Therefore, the risk of lung cancer demonstrated for these industrial groups exposed to asbestos is of such j r magnitude as to preclude the Identification of an independent etiologic role for cigarette smoking FIBER ANALYSIS IN TISSUE ,= - The physical characteristics of asbestos fibers which penetrate to the lung parenchyma have been studied by Timbrell (1965 and 1972) who demonstrated fiber respirability to be largely a function of fiber diameter. Two kinds of data are relevant. Timbrell et al (1971) and Timbrell (1972) have shown that the crocidolite mined in Northern Cape Province, South Africa, and in Western Australia is associated with a high incidence of pleural mesothelioma among the local populations and has finer and shorter fibers than the crocidolite or amosite mined in the Transvaal Province, which is associated with a relatively lower Incidence of pleural mesothelioma among the exposed population. As crocidolite and amosite are similar in chemical composition, there is reason to assume that the risk difference may be attributable to the differing physical characteristics of fibers. Preliminary studies (Fondimare et al, 1974) concerning diameter and length of 5,000 asbestos fibers from the lungs of 10 deceased persons who had been occupationally exposed, showed that these fibers were all less than 0.5 /an micrometer in diameter. When separated according to type of asbestos, 902 of chrysotile fibers and 702 of amphibole fibers were less 39 than. 5 fan in length. Asbestos bodies have been found In large numbers by light microscopy in occupationally exposed individuals (Ashcroft and Heppleston, 1973). Numerous asbestos fibers, either of chrysotlle or amphibole or both types, have been found by electron microscopy in lungs of industrially exposed men (Pooley, 1972, 1973; Fondimare et al, 1974). A quantitative topographic study of asbestos fibers in the lung has been carried out in 12 industrially exposed men which showed that heavily exposed cases with lung fibrosis and carcinomas had fewer fibers in the fibrotic lower lobes than in the less fibrotic type. In less exposed cases with lung cancer but without lung fibrosis, a higher concentration of asbestos fibers, mostly of the chrysotlle type, was clearly demonstrated in peripheral areas of the lung. Optical and electron microscopic study of pleural plaques revealed the presence of some coated fibers and large numbers of uncoated fibers, mostly short, ultimate fibrils of chrysotlle (Fondimare et al, 1974). Pooley (1973) found that 932 of 120 mesothelioma cases studied had asbestos fibers in their lungs visible by electron microscopy versus less than 502 of 135 nonmesothelioma cases. Higher concentrations of fibers were observed in mesothelioma than in nonmesothelioma cases. In mesothelioma cases, the fiber types were either amphibole or chrysotlle, or both, but amphibole was predominant; in nonmesothelioma cases, chrysotlle fibers were predominant. In the three cases included in the study by Fondimare et al (1974), the percentage of chrysotlle fibers was from 44 to 972 in the peripheral areas of the lung. The ratio of amphibole to chrysotlle has been found to decre ie from the central toward the OO ^ ^ 40 peripheral areas of the lung (Fondimare et al, 1974; LeBouffant et al, 1976). Coated fibers ("asbestos" or "ferruginous bodies") have been found in the lungs of most adults who have lived in urban areas (Gross et al, 1969; Bignon and Gonl, 1969; Selikoff et al, 1972; Thompson et al, 1966; Davis and Gross, 1973; Oldham, 1973). The number of coated fibers in the lung has been compared in cases with and without lung carcinoma. Meurman (1966), who took cigarette significant difference. consumption into accoupx,-- cot^dnfifltf > MG i .' >' < --`,j " * j^lQT J,jC FROM PPG FILE sVj Doniach et al (1975) found an increased incidence of asbestos bodies in men with stomach cancer and in women with breast cancer, but not in lung cancer cases. Warnock and Churg (1975) found that lung cancer cases had more coated fibers in their lungs, even though only one case had known occupational exposure. The variations in percentage are probably from methodologic differences. In general, methods involving the counting of fibers/unit of weight or volume of lung tissue have greater associations with health outcomes in epidemiologic studies. However, coated fibers are not specific to asbestos (Gross et al, 1968) and cannot be related to asbestos unless the core has been identified as such by electron diffraction and/or x-ray analytical techniques (Pooley, 1970, 1975; Langer and Pooley, 1973, 1974; Fondimare et al, 1975). Transmission electron microscopy has demonstrated the presence of chrysotile fibers or fibrils in the lungs of most consecutive autopsy cases in London (Pooley et al, 1970), New York (Langer et al, 1971) and Pittsburgh (Gross et al, 1973). Although some differences in both the fibrotic and the carcinogenic GO \ 41 J BbJq005229* responses to asbestos fibers may depend on the type of fiber administered, all types have definitely shown both these kinds of action (eg, Karacharova et al (1979), Shin and Firminger (1973), Wagner et al (1976). Godwin and Jagatic (1970), Gross et al (1973), and Taskinen et al (1973) reported finding fibers in lymph nodes and in the spleen, abdomen, and Intestinal mucosa of occupationally exposed patients with mesotheliomas and pleural nodules. These findings emphasize the practical importance of penetration and transport of the small fibers of asbestos from their initial sites of impaction. They also stress the importance of guarding against the entrance of asbestos fibers into the body by any route. 42 | BB 0005230 | REFERENCES FOR CHAPTER III 1. Hendry NW (1965): The geology, occurrences, and major uses of asbestos. Ann N Y Acad Sci 132:1-766 2. Hueper WC (1966): Occupational and environmental cancers of the respiratory system, in, Rentchnick P (ed): Recent Results in Cancer Research, 3, New York, Springer-Verlag, 1966, p 38 3. 1970 Report of the Departmental Committee on Compensation for Industrial Diseases. C.D. 3495, 3496, London. Her Majesty's Stationery Office 4. Hoffman FL (1918): Mortality from respiratory diseases industry trades (Inorganic Dust), bulletin 231. US Dept of Labor, Bureau of Labor Statistics, 1918, pp 176-80 5. Pancoast HK, Miller TG, Landis HRM (1917): A roentgenologic study of the effects of dust inhalation upon the lungs.., ^-Trana-" Assoc'- ''As?' ' Physicians 32:97-108 NU i : 6. Cooke WE (1927): Pulmonary asbestosis. Br Med J p}0)?4*-.Z5 : - - `' 7. McDonald S (1927): 2:1025-26 Histology of pulmonary asbestosis. Br Med J 8. Mills RG (1930): Pulmonary asbestosis; Report of a case. Minn Med 130:495-99 9. Lynch KM, Smith WA (1930): Asbestosis bodies in sputum and lung. JAMA 95:659-61 10. 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Presented at the Conference on Asbestos Disease, Rouen, ^ 1' -- France, October 27, 1975. 'Jj .s Newhouse ML, Berry G (1975): The risk of developing mesothelial tumors among workers in an asbestos textile factory. Presented at the XVIII International Congress on Occupational Health. Brighton, England, 14-19 Sept. 62. Wagner JC (1960): Diffuse pleural mesothelioma and asbestos exposure in the Northwestern Cape Province. Br J Ind Med 17:260-71 J 63. Harrington JS, Gibson JC, Wagner JC (1971): mesothelioma in man. Nature (L) 232:54 Asbestos and 64. Webster I (1973): Malignant pleural mesothelioma in an asbestos worker. Med J Aust 49:952 65. McNulty JC (1962): Malignant pleural mesothelioma in an asbestos worker. S Afr Med J 47:165 66. Jones JFP, Pooley FD, Smith PG (1976): Factory populations exposed to crocidolite asbestos. A continuing survey IARC regist. meeting, (in press) 67. McDonald JC (1973): Asbestosis In Chrysotile mines and mills, in Bogovski P, Gilson JC, Timbrell V, Wagner JC, (eds): Proceedings of the Conference on Biological Effects of Asbestos. Lyon, 1973, pp 312 68. McDonald JC, Becklake MR, Gibbs GW, McDonald AD, Rossiter CE (1974): The health of chrysotile asbestos mine and mill workers of Quebec. Arch Environ Health 28:61 69. McDonald AD, McDonald JC (1976): Epidemiologic studies of the illnesses due to asbestos in Canada. Rev Fr Mai Resp 4:25 (Supp 2) 47 i_^000523i~J 70. Kogan FM, Guselnlkova NA, Gulevskaya MR (1972): The cancer mortality rate among workers in the asbestos industry of the Urals. Gig Sanit 37:29 71. Enterline P, Henderson V (1973): Type of asbestos and respiratory cancer in the asbestos industry. Arch Environ Health 27:312 72. Borow M, Conston A, Livernese L, Schalet N (1973): Mesothelioma following exposure to asbestos: A review of 72 cases. Chest 64:64146 73. Gillam JD, Dement JM, Lemen RA, Wagoner JK, Archer VE, Blejer HP (1976): Mortality patterns among hard rock gold miners exposed to an asbestiform mineral. Ann NY Acad Sci 271:345-352 74. Seidman H, Lilis R, Selikoff I (1976): Short-term asbestos exposure and delayed cancer risk. Third International Symposium Detect. Prevent. Cancer, New York, 26, April - 1 May, 1976 75. Meurman L, Kiviluoto R, Hakama M (1974): Mortality and morbidity among the working population of anthophyllite asbestos miners in Finland. Br J Ind Med 31:105 O CO at '3 76. Kiviluoto R (1960): Pleural calcification as a roentgenologic sign of nonoccupational endemic anthophyllite-asbestosis. Acta Radiol Suppl 195:1 77. Meurman L (1966): Asbestos bodies and pleural plaques in a Finnish series of autopsy cases. Acta Pathol Microbiol Scand Suppl 181:1 _ 78. Selikoff IJ (1974): Epidemiology of gastrointestinal cancer._ Environ Health Pers 9:299 /j '1 . 79. 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Newhouse ML, Berry G (1973): Lancet 2:615 Asbestos and laryngeal carcinoma. 86. Anderson HA, Lilis R, Daum SM, Fischbein AS, Selikoff IJ (1976): Householdcontact asbestos neoplastic risk. Ann N Y Acad Sci 271:311,23 87. Wagner JC, Sleggs CA, Marchand P (1960): Diffuse pleural mesothellma and asbestos exposure in the North-Western Cape Province. Br J Ind Med 17:260 88. Newhouse ML, Thompson H (1966): Mesothelioma of pleura and peritoneum following exposure to asbestos in the London area. Br J ~'T Ind Med 22:261 89. Bohlig H, Hain E (1973): Cancer in relation to environmental ' exposure, type of fibre, dose, occupation and duration of exposure, in Bogovski P, Gilson JC, Timbrell V, Wagner JC, (eds): Proceedings of the Conference on Biological Effects of Asbestos. Lyon, 1973, pp ' 217 90. Gilson JC (1970): Asbestos health hazards. Recent observations in the United Kingdom, in Shapiro HA (ed): Pneumoconiosis. Proceedings of the International Conference, Johannesburg, Cape Town, Oxford University Press, 1970, pp 173 91. Greenberg M, Lloyd Davies TA (1974): Mesothelioma register 1967-:1968. Br J Ind Med 31:91 92. Selikoff IJ, Hammond EC, Churg J (1968): Asbestos exposure, smoking and neoplasis. JAMA 204:106 93. Doll R (1971): The age distribution of cancer: Implications for models of carcinogenesis. J R Stat Soc A 134:133 94. Berry G, Newhouse ML, Turok M (1972): Combined effects of asbestos exposure and smoking on mortality from lung cancer in factory workers. Lancet 2:476 95. Hammond EC, Selikoff IJ (1973): Relation of cigarette smoking to risk of death of asbestos-associated disease among insulation workers in the United States, in Bogovski P, Gilson KC, Wagner KC (eds): Proceedings of the Conference on Biological Effects of Asbestos. Lyon, 1973, pp 312 49 ? NOT COiVit THOM PPG FILES 96. Lemen RA (1976): Lung cancer in female asbestos workers. Letter to Vernon Rose, Director, Division of Criteria Documentation and Standards Development 97. Timbrell V (1965): The inhalation of fibrous dusts. Ann NY Acad Sci 132:255 ' 98. Timbrell V (1972a): Alignment of amphibole asbestos fibres by magnetic fields. Microscopy 20:365 99. .100 .101 Timbrell V, Griffiths DM, Polly FD (1971): Possible biological importance of fibre diameters of South Africa amphlboles. Nature (London) 232:55 Timbrell V, Rendall REG (1972b): Preparation of the UICC standard reference samples of asbestos. Powder Technol 5:279 Sebastian P, Fondimare A, Bignon J, Moncheax G, Desbordes J (1975): Topographic distribution of asbestos fibers in human lungs in relation to occupational and nonoccupational exposure. Presented at the Symposium on Particles and Vapors at Edinburgh, Scotland. September 1975 C2i x;-' UJ 102. Ascroft T, Heppleston AG (1973): The optical and electron microscope -O determination of pulmonary asbestos fibre concentration and its C.~- relation to the human pathological reaction. J Clin Pathol 26:224 103. Pooley FD (1972): Asbestos bodies, their formulations, composition and character. Environ Res 5:363-79 104. Pooley FD (1973): Mesothelioma in relation to exposure, in Bogovski P, Gilson JC, Timbrell V, Wagner JC (eds): Proceedings of the Conference on Biological Effects of Asbestos. Lyon, 1973, pp 99 105. Fondimare A. Desbordes J, Perrotey J (1974): Etude semi quantitative de l'empoussierage par l'amiante dans 14, Arch Anat Pathol, (Paris) 22:55 106. Le Bouffant L, Martin JC, Brueres S, Tichoux G, Normand C (l/76): Quelques observations sur les siches d'amiante et formations anomalies rencontrees dans les poumons asbestosiques, lapathologie de l'amiante symposium 27~28 Oct. 1975, Rouen, France 107. Gross P, de Treville RTP, Haller MN (1969): Pulmonary ferruginous bodies in city dweller. A study of their central river. Arch Environ Health 19:186 108. Bignon J, Goni J (1969): Pulmonary ferruginous bodies in France. Am Rev Resp Dis 101:804 hi r . -PI 50 109. .110 Selikoff IJ, Hammond EC, Churg J (1972): Carcinogenicity of amosite asbestos. Arch Environ Health 25:183 Thomson JG, Gross P (1973): Are ferruginous bodies an indication of atmospheric ppllution by asbestos? in Bogovski P, Gilson JC, Trimbrell V, Wagner JC (eds): Proceedings of the Conference on Biological Effects of Asbestos. Lyon, 1973, pp 238 111. .112 Davis JMG, Gross P (1973): Are ferruginous bodies an indication of atmospheric pollution by asbestos?, in Bogovski P, Gilson JC, Timbrell V, Wagner JC (eds): Proceedings of the Conference on Biological Effects of Asbestos. Lyon, 1973, pp 238 Oldham PD (1973): A trial of techniques for counting asbestos bodies in tissue, in Bogovski P, Gilson JC, Timbrell V, Wagner JC (eds): Proceedings of the Conference on Biological Effects of Asbestos. Lyon, 1973, pp 45 113. Meurnan LO (1968): Pleural fibrocalcific plaques and asbestos O CO exposure. Environ Res 2:30 114. 115. Doniach I, Swettenham KV, Hathorn MRS (1975): Prevalence of asbestos bodies in a necropsy series in East London: Association with disease, occupation and domiciliary address. Br J Ind Med 32:16-30 Warnock ML, Churg AM (1975): Association of asbestos and ` bronchogenic carcinoma in a popuation with low asbestos exposure. . C Cancer 35:1236-42 Li_ Qrj CL. a_ 116. Gross P, de Treville TP, Cralley J, Davis JMG (1968): Pulmonary, ferruginous bodies. Arch Pathol 85:538-46 117. Pooley F, Oldham P, Um Chang-Hynn, Wagner JC (1970): The detection. f of asbestos in tissues, in, HA Shajsiro (ed) : Pneumoconiosis, :--, Proceedings International Conference Johannesburg, Capetown, Oxford, . University Press, 1969, 108 pp --II ^ 118. Pooley FD (1975) : The identification electron microscope micro-probe analyses. 1975 (in press) of asbestos dust with an Ann Occup Hyg 18:181-86, 119. .120 Langer AM, Pooley FD (1973): Identification of single asbestos fibres in human tissues, in Bogovski P, Gilson JC, Timbrell V, Wagner JC (eds). Proceedings of the Conference on Biological Effects of Asbestos. Lyon, 1973, pp 119 Langer AM. Mackler AD, Pooley FD (1974) : Electronmicroscopical investigation of asbestos fibres. Environ Health Pers 9:63 121. Langer AM, Selikoff IJ, Sastre A (1971): Chrysotile asbestos in the lungs of persons in N.Y. City. Arch Environ Health 22:348-361 51 122. Gross P (1974): Is short-fibered asbestos dust a biological hazard? Arch Environ Health 29:115-117 123. Karacharova VN, Ol'shvang RA, Kogan FM (1969): Changes in certain organs after experimental introperltoneal injection of asbestoscontaining dusts. Byull Eksp Biol Med 67:117-120 124. Shin ML, Firminger HI (1973): Acute and chronic effects of introperltoneal injection of two types of asbestos in rats with a study of the histopathogenesis and ultra structure of resulting mesothelioma. Am J Pathol 70:291-314 125. Godwin MC, Jagatic J (1970): Asbestos and mesotheliomas. Environ Res 3:391-416 126. Gross P, Davis JMG, Harley RA, deTreville RTP (1973): Lymphatic transport of fibrous dust from the lungs. J Occup Med 15:186-189 127. Taskinen E, Ahlman K, Wiideri M (1973): A Current Hypothesis of the lymphatic transport of inspired dust to the parietal pleura. Chest 64:193-196 J\JQTP rori 'MTMJ QJQ NOT CCYi rVG TiLES 52 \ Un U> -'i ai U'M o oO II oI tr l to l CO !:i CH CO *..dLE III-l STUDIES OF HUMAN POPULATIONS-NONMALIGNANT RESPIMTORY DISEASE m Author Hlator teal Studlea Hurray Cooke McDonald Ml 11a Lynch and Smith Epidemiological Studlea Hurphy Lorlaer et al Meurman ec al Weill et al Ayer and Burg Sellkoff Anderaon ec al Wagner et al Kevhouae Enter!Ine and Henderaon SellkoK Buha Lewlnaohn Cl 1 lam at al Date Finding Croup and Exposure 1906 1927 1927 1930 1930 First reported case of asbestoala Case of asbestoala reported Two cases of asbestosIs reported First case of asbestosls reported In ll.S. Ferruginous or "asbestoala bodies" found In sputum Asbestostl workers II 91 1971 1976 1973 1975 1976 1976a 1976 1971 1969 1973 1976a 1966 Asbestosls X-ray abnormalities consistent with with asbestosls and restrictive pulmonary function testing Dyspnea and cough Decreased lung function Decrease in pulmonary function Asbestosls X-rays consistent with asbestosls Death due to nonmallgnsnt' respiratory disease and diseases of heart, In part secondary to pulmonary disease Death due to nonmallgnsnt respiratory dlaeaae Death due to asbestosls X-ray evidence of asbestos 1972 1976 X-ray abnormalities Nonaullgnant respiratory dli Pipe insulators Brake repair maintenance workers Asbestos workers Asbestos cement manufacturing workers Asbestos textile workers with less than 10 yr exposure Former Insulation plant employees with as little as one day exposure Household and family members of asbestos worker Chrysotlle workers Hale asbestos textile and Insulation workers Asbestos plant workers Insulation workers and factory workers exposed to asbestos Workers In asbestos Industry in Britain after 1933 with perponderance of less thsn 20 yr exposure Aebeetoe worker* in Brltlan Aatoelte miner* NOTE: NO i C GCLIML'NTDID ,...i PPG FILES m TABLE III-2 STUDIES OF HUMAN POPULATION CARCINOGENICITY Author Occupat tonal Exposure Historical Studies Lynch and Smith Cloyne Uedler Doll Kancusco and Coulter Sellkoff Epidemiclogical Stud lea Lung, Pleural and Peri toneum Hlxed Types of Fibers Newhouse (UK) Boh 1Ig et al (FRG) Sellkoff et al (USA) Elmes and Simpson (UK) Stumphlua (Netherlands) RubIno et al (Italy) Selikolf et al Enterllna and Henderson Harries Edge V jD l Date Finding Group and Exposure 1933 Suspicion of association Asbestos workers 1933 I943a,b Between asbestos and lung cancer Case reports of pleural and peritoneal tumors associated to asbeBtoa II (1 1955 Lung cancer Asbestos textile workers employed before 1930 1963 1966 Lung cancer and mesothelioma* *1 Asbestos workers 1 1969 1910 1970 1971 1971 1972 1973 1973 1976 1976 Bronchial cancer, pleural peritonealmesotheliomas ^ SSL oo and" - \ "'"4 ^i v' - ii Lung esneer '* ' ) > Asbestos manufacturing. Insulation and shipyard workers M II * II *1 Insulation workers, chrysotlle and amoslte asbeBtoa exposure Respiratory cancer Retired production and maintenance * - tM workers In asbestos industry Mesotheliomas Carcinoma of bronchus . ' i.. ~v'' 1-- ni Uj J Naval dockyard worksra Shipyard worksra "} `J BB 0 0 0 5 2 4 2 TABLE III-2 (CONTINUED) STUDIES OF HUMAN POPULATION CARCINOGENICITY Author Date Hliied Types of Fibers DeLajarte et al (Franca) 1973 Cobbato and Ferrl (Italy) Uebater (South Africa) Greenberg and Lloyd Davies (UK) Hatn et al (Fed. Rep. Germany) Nurmlnen (Finland) Stunn (Cer. Dem. Rep.) Zlelhula (The Ketherlanda) 1973 1973 1974 1974 1973 1973 1973 Neuhouae et al 1973 ui <_n ClIson 1973 Hammond and Sellkoff Sellkoff 1973 1976 Newhouse and Berry 1973 Single Types of Fibers Ctocldol1te Uagner 1960 i I 1 I in BB 0 0 0 5 2 4 3 1 I I I 1 I C-O I I I I II II Harrington et al Webster HcNully Jones et al 1971 1973 1961 1976 Finding Evidence of association between mesotheliomas and past exposure to asbestos H ii ii Group and Exposure Occupational exposures in some cases as brief as one day l II n Peritoneal tumors associated to heavy exposures 3Z to 7X asbestos workers' deaths due to mesotheliomas 111 asbestos workers deaths due to mesotheliomas 22 Oo . i --rn"1 Pleural and peritoneal cancer Workers In mines, mills and In - transportation and handling of j y crocldollte and population In vicinity of mines Mesotheliomas Mining population of crocldollte 3 lnM -- / 'Miners of crocldollte * . .if^Woman working with crocldollte In --pfWn.1 gas mask canister factories ~n --I rrn o-c/j o P TABLE III-2 (CONTINUED) STUDIES OF HUMAN POPULATION CARCINOGENICITY > BB 0 0 0 5 2 4 4 V..a O' i-- i ii i i i I i 1 i >i i-- i Author Date Finding Croup and Exposure Chryaot fle HcDonald et al Kogan et al Wagoner et al Enterllne and Henderaon Borov et al jUaoS11 e Gilllan et al ' c^ ___ _ .- Sellkoff et al Anthophylllte Neuman et al Other Cancer Hancuso and El Altar Elmes and Slmpaon Kogan et al Newhouse Wagoner et al HcDonald et al Sellkoffetal Stell and HcClll Morgan et al Nevhouaa and Perry 1971,1974 1972 1973 Lung cancer Total cancer Lung cancer' Reaplratory cancer 1973 n 1973 Meaothelloaas Chryaotile sine and aill workere Workers in asbestos mining snd Billing, men snd women Workers In manufacturing of textile, friction and packaging products using chrysotlle Ken 65 yr and older, retired production or maintenance eaployeea In asbestos Industry exposed only to chrysotlle Workers at plant using chrysotlle, all ages 1976 Kallgnant reaplratory dleeaae 1976a,b Kesothelloeaa, lung cancer Klners exposed to amphlbole fibers in cuaalngtonlts-grunerlts ora series Insulation worker* in factory using aaosite 1974 1967 1971 1972 1973 1973 1974 1974 1973 1976 1973 Bronchial cancer, dyepnea and cdugh -J Anthophyl llts mining employees V. - - ' i Cancer of gastrointestinal tract? ~ l n V i ........... SAsbestos workers i" }M it Squamous carclnoaa of larynx Cancer of larynx ,\ -- . .Workers with exposure to Jaabeato* ' ^ ; ^Asbestos workers f-j ji -ys* t" :;j n-1 -- 4 t/t t: IOI IO I^1 1 to \ *1$ U'l TABLE III-2 (CONTINUED) STUDIES OF HUMAN POPULATION CARCINOGENICITY Author Honoccupatlonal Exposure Anderson et el Wagner et al Newhouse and Thoapaon Bohlig and Haln Cl Ison Creenburg and Lloyd Davies Klvlluoto Other Studies Newhouse Newhouse et al Howard et al Cooper et al Da to Finding Croup and Exposure 1975 1960 1965 1973 1970 1976 1960 Meaothelloaae 19 II Pleural plaques 19691971 1976 1975 OM ----1 -* 'i Cancer, aeaothalloaa --*'"* /1 Lung cancer O -'"i pTi <Y3 O -O y* rn CD l- 1 -o I ,___ I CO Faaily aeabers of asbestos workers Individuals In neighborhood of Industrial sources of asbestos Hew esses froa areas with recognlred Industrial sourcs of asbestos Persona In faralng region of Bulgaria where alnute quantities of anthophylllte, treaollte and .seplollte In soil, and nonoccupatlonally exposed persona in anthophylllte Mining area of Finland Waaen factory workers exposed to chryaotlla, aaoslte and crocldolita Workers In asbestos Industry froa 1933 to 1950 and aftsr 1950 Sheet aatal workers with 5 or sore yaara exposure IV. SAMPLING METHODS AND ENVIRONMENTAL DATA Review of Sampling and Analysis Techniques for Asbestos A variety of sampling and analysis techniques have been used to identify asbestos fibers and determine their concentrations in air, water, mineral samples, and biologic tissue. These include optical and electron microscopy, x-ray diffraction, and differential thermal analysis. Asbestos fiber identification and quantitation in occupational and environmental air samples is difficult for a variety of reasons: 1) Asbestos fibers are generally present in low mass quantities even though fiber number concentrations may be high. 2) Many instrumental analytical techniques cannot differentiate asbestos fibers from their nonfibrous mineralogic polymorphs. CS CO -- 1-1-1 o f"* i.JL. UJ ^ 3) Many airborne asbestos fibers are generally below resolution limits of the optical microscope. These fibers may only be detected by using electron microscopic methods. A) For identification of the various asbestos fiber types by electron microscopy, electron diffraction and microchemical analyses must be performed which require expensive instrumentation and analysis time. (a) Electron Microscopy and Microchemical Analysis Both transmission and scanning electron microscopy have been used for asbestos fiber identification and quantitation. In addition to morphologic observation, selected area electron diffraction and microchemical mn58 go "bB-00 05 24 6 | analytical techniques may be used for fiber identification. In addition to superior resolution capabilities, most modern transmission electron microscopes are equipped with electron diffraction facilities. Crystalline materials scatter electrons in regular patterns related to their crystal structure. The image of the scattered electrons is mainly predicted by Bragg geometry. In the transmission electron microscope, the diffraction image is formed in the back focal plane of the objective lens and is focused in the viewing screen by defocusing the intermediate lens. Visual observation of single fiber (single crystal) electron diffraction patterns may be used to differentiate chrysotile fibers from amphibole fibers (Langer et al, 1974; Timbrell 1970). Chrysotile fibers produce streaked diffraction patterns (lattice defects), with the streaks or layer lines nearly perpendicular to the fiber length. The spacing between the layer lines denotes the fiber "a" axis of o approximately 5.3 A. Reflections along the layer lines are usually very streaked and Debye-Scherrer rings are common. With progressive electron beam bombardment, the diffraction pattern may change because of fiber damage. The "central core" of chrysotile fibers may also aid in fiber identification with the precaution that the central core is not always discernable and may disappear with the beam damage (Langer et al, 1974). Also, other fibrous minerals may have hollow cores. The amphibole minerals are generally straighter in appearance than chrysotile fibers. Moreover, light and dark banding (diffraction images) may cross the fiber at right angles (Langer et al, 1974). Diffraction contrast figures have been observed on all amphibole fiber types. Selected area diffraction patterns for the amphibole asbestos minerals are all O C/3 i ] o 3 59 J BB 0005247 similar In appearance; therefore, visual observation of these patterns is sufficient only to classify the fiber as being a fibrous amphibole (Langer et al, 1974; Cook et al, 1974). Amphibole electron diffraction patterns show layers and sometimes streaks perpendicular to the fiber length with the spacing between the layer lines or streaks representing the fiber Mc" axis (Langer et al, 1974) of approximately o 5.3 A. In contrast to chrysotile, less streaking along the layer lines is observed with the spot repeat along the lines representing one of the two remaining lattice spacings ( "b" or "a") depending on fiber orientation relative to the electron beam. Typically, approximately 30 seconds is needed to perform cn selected area electron diffraction analysis on a single fiber. izi H" LU In addition to visual observation of electron diffraction patternj^ C3 for fiber identification, photographs can be made of the diffraction^ * ^^m patterns and crystal "d" spacings measured from the plate and calculate^-k CIl using the instrument camera constant (Timbrell, 1970). Both "spot" and. . ;, , polycrystalline patterns may be measured. It must be borne in mind thatr_- ;j* intensities may not be the same as those observed for x-ray powder pattern^jj CD and additional reflections may be present. CD CD Electron beam microchemical analytical techniques may sometimes be used to identify asbestos fibers from other fibrous particles (Rubin and Maggiore, 1974; Ferrell et al, 1975; Langer et al, 1975; Maggiore and Rubin, 1973). The most common system presently in use is the energy dispersive x-ray detector in combination with a scanning or transmission electron microscope. Wavelength x-ray analyzers and the conventional electron microprobe have been used; however, their routine application is limited because of data acquisition times (Langer et al, 1975^-Q 60 L^00052U8'J other hand, data acquisition times with energy dispersive analyzers are far less, ranging from 20 to 80 seconds/analysis. Semlquantitative microchemical analysis in the electron microscope is based on the fact that a beam of high energy electrons incident on an asbestos fiber generates x-rays characteristic of the elements present in that fiber. The generated x-rays are observed by means of a detector (lithium-drifted silicon crystal) placed in the electron microscope column close to the specimen. The energy of the x-ray photon is converted to a voltage pulse which is amplified, digitized and stored in a multichannel analyzer or a minicomputer. The content of the memory is usually displayed on a CRT (Maggiore and Rubin, 1973). With the energy dispersive detector, all elements with atomic numbers of sodium or higher may be analyzed. Continuous background or brehmsstrahlung radiation is always present with the x-ray spectrum. Each of the asbestos minerals has an x-ray spectrum which is usually characteristic enough, when combined with fiber morphology, to allow Its identification (Rubin and Maggiore, 1974; Ferrell et al, 1975; Dement et al, 1975). Visual observation of the semlquantitative fiber x-ray spectra is usually sufficient for fiber identification; however, three component diagrams have been used after subtracting the continuous background from the semiquantltative x-ray spectrum (Ferrell et al, 1975). For asbestos fiber analysis, matrix corrections are rarely used. Typically, iron, magnesium, and silicon are plotted on the three component diagram and compositional boundaries for the asbestos minerals established. This technique suffers from inability to use all compositional data obtained, such as presence or absence of sodium, calcium, aluminum and manganese. which aid in identification. 61 7BB 0005249.1 With energy dispersive x-ray techniques, p ssesslon f pr per elemental Intensities may not be sufficient for positive Identification as many fibrous minerals show similar elemental Intensities. For example, chrysotile, anthophyllite, and fibrous talc, which have similar elemental compositions, may be difficult to differentiate. However, these materials may easily be distinguished by using selected area electron diffraction. In addition, unique Identification of the various fibrous amphlboles usually requires both selected area diffraction and microchemical analysis. Transmission electron microscopes equipped with an energy dispersive x-ray detector are now available which allow simultaneous morphology, crystal structure, and elemental composition. observation of o cn -- m These microscopy^""*) ^ systems have been used to study asbestos fibers in environmental material samples. (Cook et al, 1974; Dement et al, 1975) H" ij-- and'")^ ! jU ' P Quantitative analysis of asbestos fiber concentrations lit. environmental and tissue samples has been accomplished by electroii-- \/. microscopy. Environmental samples (water and air) are generally collected*, by first concentrating the sample by filtration, centrifuging, etc (Cook et. . O al, 1974; Nicholson, 1974). The filters (Millipore) and polycarbonatq^T filters (Nuclepore) are prepared for electron microscopic analysis by various methods. For scanning electron microscopy, Nuclepore filters, because of their smooth surface, may be directly coated with an appropriate metal (gold, etc) and analyzed (Porter and Berggren, 1974). Millipore filters have a rough surface texture and are not generally suitable for direct coating for scanning electron microscopy as small fibers may escape detection due to impaction below the filter surface (Nicolson, 1974). GG 1 -377 62 I BB 0005250 For transmission electron microscopy, the filter substrate must be removed and the particles mounted on suitable electron microscopy grids. A wide variety of mounting techniques have been used. The two most commonly used methods are the Jaffe Wick and condensation washing techniques. The techniques offer simplicity In addition to maintaining the original particle size distribution of the sample. Different investigators have reported particle losses up to 60% with Millipore filters while using the condensation washing method with rapid filter dissolution, whereas losses with the Jaffe Wick method have been reported to be considerably less (>10%) (Beaman and File, 1975). Lesser particle loss has been observedf^ </) with the condensation washing method when longer times for dissolution of*--* TM the filter are used. Ortiz and Loom (1974) reported that a modification off the Jaffe Wick method, whereby the filter is first coated with silicon1' monoxide and carbon by vacuum evaporation prior to dissolving the Millipore filter, minimized particle loss. Several investigators have reported minimal particle loss with Nuclepore filters when the filter is first V carbon-coated prior to dissolving the filter substrate (Cook et al, 1974; f Maggiore and Rubin, 1973). ' In addition to the so-called direct clearing/mounting techniques mentioned above, many other techniques have also been used" for preparing environmental samples. Seikoff et al (1972) have used a so-called "rub- out" technique whereby the Millipore filter is ashed in a low temperature asher to remove organic or carbonaceous material. The residue is then dispersed on a microscope slide using a solution of 1% Nitrocellulose in amyl acetate. After grinding with a watch glass to liberate individual fibers, the sample is dispersed evenly between two microscope slides to GC M373 63 Tbs' 000525 form a thin film which is transferred to standard electron microscope grids. Particle losses averaging 50Z have been reported with this technique. This technique also increases the apparent number of fibers present due to breaking up of fiber bundles. Asbestos fiber levels in environmental samples and biologic tissue are usually expressed as asbestos fibers/unit volume of sample (fibers/m3, fibers/liter, fibers/g dry lung, etc). These concentrations are determined by counting fibers within calibrated areas on the electron microscope viewing screen or counting fibers from photographs. Asbestos fiber concentrations in water samples determined by laboratories using the same mounting techniques have been reported to vary by a factor of 2-3 (Cook et al, 1974). Much larger variations have been reported between laboratories using o^ different ' techniques Asbestos mass (chrysotile) concentrations in environmental samples -' have also been determined using electron microscopy. This is accomplished ' by measuring the length and diameter (volume) of each fiber and calculating r; the mass using the appropriate density (Selikoff et al, 1972). The accuracy of this technique has not been studied in detail. Electron microscopic techniques methods for asbestos fiber analysis. represent However, '-z-iJ the "best available" - O' application of these techniques to routine samples is not practical because of extremely high analysis costs ($200~$400/sample), long analysis times, and equipment availability. limited (b) X-Ray Diffraction X-ray powder diffractometry is one of the standard mineralogic techniques used in the analysis of solid crystalline phases. X-ray 64 | BB 0005252 diffraction has been widely used for Identification and quantltatl n of asbestos fibers In bulk materials such as talc (Stanley and Norwood, 1974; Rohl and Langer, 1974) and other Industrial materials (Crable and Knott, 1968; Keenan and Lynch 1970). X-ray diffraction has also been used to study amphibole asbestos contamination of water samples (Cook et al, 1974). X-ray diffraction la generally considered more sensitive for asbestos than light microscopy, although less sensitive than electron microscopy (Rohl and Langer, 1974). Diffraction lines and relative intensities for each of the asbestos minerals have been published and may be found in the ASTM Powder Diffraction File. Variations in asbestos fiber chemical composition, Q GO i11 i especially for the amphlboles, may result in slight peak shifts from reported x-ray diffraction data. Quantitative determinations of asbestos fiber levels in material samples (talc, etc) require that particle size first be reduced to an D average of 0.1-10 fm. Preferred orientation and surface roughness must also be eliminated. A number of techniques have been used to minimize preferred orientation effects including binder and slurry mounting methods, sifting and backloading of dry powders, and several others. To minimize preferred orientation, Rohl and Langer (1974) have developed a method for filtering an aqueous slurry through Millipore filters using a filtration adapter attached to a hypodermic syringe. Other investigators have used the backloading technique with multiple x-ray diffraction scans. Using conventional scan rates (0.5 - 1 degree 2 theta/minute), lower limits of detection of asbestos by x-ray diffraction of 5% in bulk samples 65 rc \ i BB 0005253 J have been reported (Crable and Knot, 1966). Automated step scanning procedures by which diagnostic reflections are slowly scanned and Integrated counts recorded have been reported to significantly reduce detectable limits. Rohl and Langer (1974) have detected anthophyllite at 2.0Z, chrysotile at 0.25/C, and tremollte at 0.10Z by wleght in a talc matrix using external dilution standards for calibration. Similar lower detectable levels have been reported by Stanley and Norwood (1974). Application of x-ray diffraction for routine asbestos fiber analysis of environmental samples has been limited. Birks et al (1975) have reported a feasible study concerning quantitative analysis of airborne O CO " tU asbestos. Their technique Involved alignment of the asbestos fibers in an O .~4 electrostatic field to enhance counting in a specially designed diffraction diffraction intensity followed by x-ray t apparatus with two x-ray j detectors. A lower limit of detection of 0.4 - 0.5 Mg was reported. This technique has not been applied to actual environmental samples. Amphibole and cummingtonite-grunerite mass concentrations in water samples have been semiquantitatively determined using x-ray diffraction with step scanning (Cook et al, 1974). This technique involves filtering the water through 0.45-Mni Mlllipore filters followed by step scanning a major amphibole diffraction peak (110) and a peak specific to cummingtonitegrunerite (310). The integrated peak count above background is recorded and mass concentrations are determined using external dilution standards. Proper selection of diagnostic reflections to maximize detection sensitivity and minimize interference due to other mineral phases is necessary for proper use of x-ray diffraction. It must also be recognized 66 J'J I ^ BB 0005254 f that x-ray diffraction methods are not capable of differentiating between asbestos fibers and their nonflbrous mineralogic polymorphs. This fact, combined with relatively poor detection levels, suggests that alternate techniques such as electron microscopy should be combined with x-ray analysis. (c) Differential Thermal Analysis Differential thermal analysis has been used to determine asbestos fiber levels in talc samples (Schlez, 1974) Chrysotlle (serpentine minerals) shows a dehydroxylatlon endotherm at approximately 650 degrees C and an exotherm at approximately 820 degrees C, associated with the formation of forsterite. These peaks may be used for quantitative Q C/5 analysis. Using a 140-mg sample holder with an exposed loop differential thermcouple and a 10 degree C/minute heating rate, Schlez (1974) reported 'V' that a 1% concentration of chrysotlle could be detected in pharmaceutical grade talc. A dynamic helium atmosphere was maintained to sweep out gaseous mineral decomposition products and to prevent oxidative reactions. Differential thermal analysis has not been used for environmental samples as lower limits of mass detection are extremely poor. Differential thermal analysis, like x-ray diffraction, is not capable of differentiating between asbestos fibers and their nonfibrous mineralogic polymorphs. (d) Optical Microscopy A number of optical microscopic techniques have been used to identify and/or quantitate asbestos fibers in environmental samples. These include petrographic and phase contrast microscopy. Petrographic microscopic techniques may be used to identify asbestos fibers greater than approximately 0,2 - 0.3 m in diameter. Using the polarizing microscope. " JLt 67 I BB 0005255 | various optical crystallographic measurements such as refractive index, extinction angles, and sign of elongation may be measured and compared with data reported for standard asbestos reference samples. Typical optical data for selected asbestos minerals are shown in Table IV-1 (Julian and McCrone, 1970). Dispersion staining with polarized light has been used to identify asbestos fibers, as reported by Julian and McCrone (1974). With this technique, the fibers are immersed in a mounting medium with a steeper dispersion curve than the fibers. A central or annular stop is used in the objective lens back focal plant to allow either the wavelength of light at which the index of the particle matches that of the mounting media, or complements to that color to reach the observer's eye. Using plane polarized light, asbestos fibers show two characteristic dispersion staining colors; one for the light vibration parallel to and the other for that perpendicular to the fiber length. The dispersion colors depend on the refractive index media in which the fibers are mounted, as shown in Table IV-2. Dispersion staining colors may change slightly depending on the geographic area from which the asbestos was mined and subsequent treatment. Fibers less than 0.5 (m in diameter may not be identified by this technique because of difficulties in distinguishing colors. Phase contrast optical microscopy is the technique specified for determining the Occupational Safety and Health Administration asbestos standard (US Department of Labor 1975). The method consists of collecting breathing zone samples during 15-minute to 8-hour periods on membrane filters (millipore AA). Samples are analyzed by first clearing the membrane filter to make it optically transparent, then by fiber counts at ) f nr n 68 JL .; ; '<i i-- - . . .. . w i s J f i L l l S 400-5OOX magnification by phase contrast optical microscopy. Asbestos fibers are defined as those particles with a length greater than 5 pan and a length-to-diameter ratio of 3:1, or greater. This technique, by which only fibers longer than 5 /an are counted, is recognized as only an index of total fiber exposure and does not Imply that shorter fibers do not pose a health hazard. The relative proportion of airborne fibers longer than 5 /on has been shown by Dement et al (1975) to vary from 1 to approximately 50Z depending on the industrial operation and asbestos fiber type. In addition to problems of detecting short fibers, phase contrast microscopy may not be specific for asbestos fibers in industrial operation where mixed fiber types are encountered. ( Despite its limitations, phase contrast microscopy represents the only technique available that can reasonably be used for routine asbestos fiber sampling and analysis. It Is adaptable to personal sampling where low air volumes are sampled and analysis equipment is readily available. Minimum detectable fiber concentrations by phase contrast microscopy depend on a number of.factors such as air volume sampled, microscope field counting area, number of microscopic fields counted, and presence or absence of nonflbrous particles. Theoretical minimum detectable concentrations may be calculated assuming one fiber longer than 5 /an is observed per 100 microscopic fields (after filter background subtraction). Table IV-3 shows theoretical minimum detectable fiber concentrations as a function of sample period for a typical microscope arrangement. For a 15- minute sampling period, 0.04 fibers >5 /an/cc may be detected; however, with an 8-hour sample, 0.001 fibers/cc can be detected. These minimum concentrations are similar to those reported by Com and Sansone (1974). O ^__ V- H0 i L : 69 ] BB 0005257 these auth rs reported that 0.01 fibers/cc could be detected with a 2-hour sample period (40 microscopic fields counted). The above .calculations represent theoretical minimum detectable concentrations, not considering the many factors affecting precision and accuracy of the technique. There are many sources of variability in the laboratory analysis technique. The major sources of variability are as follows: 1) Variability of fiber distribution across the filter surface. O CO LiJ 2) Variability of fiber distribution on a given filter wedge being analyzed. 3) Variability due to differences between microscopes. 4) Variability due to differences between individual counters. 5) Variability in laboratories. )' Leldel and Busch (1974) found that the fiber distribution on a given ^ filter section could best be described by the Poisson-distribution.*" However, Conway and Holland (1973) found that the distribution of fibers on filters was not uniform and were more disperse than predicted by the Poisson distribution, so that concentrations between sections could vary by as much as 50-60Z. Similar results were found by Rajhans and Bragg (1975) in Series I of their study. If the Poisson distribution is taken to adequately describe fiber distributions on filter sections, the standard deviation of the fiber count may be estimated from the square root of the count. In order to maintain an acceptable Coefficient of Variation (CV) (below 20Z), a minimum of 25 fibers must be counted. For a typical industrial asbestos sample of 2 | BB 0005259 | hours (2 1pm flow), this would correspond t a concentration of 0.13 fibers/cc. The precision of the entire sampling and analysis procedure (all sources of variability) has been estimated by Leidel et al (1975). These authors estimated the total CV to be 22%. Comparisons of Asbestos Mass Concentrations (ng/rn^) and Fiber Number Concentrations (fibers/cc) In order to relate ambient asbestos levels, which are generally expressed as ng/nP, to occupational exposures, which are expressed as O CO fibers >5 im in length/cc, a conversion factor is needed. Attempts to formulate such a conversion have generally been unsuccessful because of exceptionally large variability. This is to be expected as ambient levels are generally determined using electron microscopy whereas phase contrast microscopy is used to measure occupational exposures. In addition, techniques used to prepare samples for electron microscope observation may cause alterations in fiber size (diameter and length) distributions. -:1 O .-) Lynch and Ayer (1966) presented results of environmental studies in the asbestos textile industry where fiber concentrations were determined using phase contrast optical microscopy and fiber size distributions were determined using electron microscopy. The mass of chrysotile on the filter was estimated by using atomic absorption spectroscopy to determine the magnesium content of the sample and asbestos content was calculated, assuming a 25Z magnesium content for chrysotile. These data are summarized in Table IV-4. Based on the magnesium analysis, the authors concluded that 71 | BB 0005259 | one nanogram of asbestos was roughly equivalent to five fibers greater than 5 fm in length by optical microscopy, although much variability about this value was observed. By using fiber size data determined by electron microscopy to calculate the mass of a typical fiber, the authors concluded that one nanogram of asbestos corresponded to 8 fibers (all lengths) by optical microscopy. In a subsequent paper, Lynch et al (1970) published results of count to weight comparisons for other industrial operations using the sample techniques previously described. These data are summarized in Table IV-5. Again, large variations in the relationships were observed, as evidenced by CTi large geometric standard deviations. Table IV-5 shows that one nanogram of asbestos may be roughly equivalent to 6.7 - 46.5 fibers >5 jam, depending on ij - ' the operation. In their study of asbestos contamination in commercial building, ^ Nicholson et al (1975a) compared the results of asbestos concentrations (ng/m3) determined by electron microscopy to fiber concentrations determined by phase contrast microscopy for the same samples. These data were highly variant showing no consistent relationship. One nanogram of asbestos was shown to range from none detected to 6,570 asbestos fibers >5 " m by phase contrast microscopy. By averaging data, it was calculated that one nanogram was equivalent to 52 asbestos fibers >5 ym in length. Air samples collected in communities surrounding the Reserve Mining Company, Silver Bay, Minnesota, have been analyzed by electron microscopy and concentrations expressed in ng/m3 by mass calculation and fibers/fo3 by direct counts (Nicholson, 1973). These results showed one nanogram of 72 | BB 000526CM amphibole fibers to be equivalent to 640--108*000 total amphibole fibers by electron microscopy* with an average value of 30,600 fibers/ng. A study recently published by Dement et al (1975) provides additional data for the conversion of mass concentration to fiber number for amphlboles. In this study* 22 air samples collected in an underground gold mine were analyzed by phase contrast optical microscopy and electron microscopy to determine fiber concentrations. A direct clearing technique which preserved the original fiber size distribution was used to prepare samples for electron microscopy. In addition to fiber counts by electron microscopy, each fiber was sized (length and diameter) so that the mass could be calculated (assuming a density of 2.5 g/cc). These data are summarized in Table IV-6. From these data, approximate relationships between mass concentrations and fiber count concentrations were calculated. One nanogram was calculated to be equivalent to approximately 1,200 total fibers by electron microscopy or 400 fibers >5 Aim In length by phase contrast microscopy. The above studies have not shown a consistent conversion factor for fiber mass to fiber count. Bruchman and Rubino (1975) have suggested a conversion ratio of 20 asbestos fibers >5 fm in length, as determined by optical microscopy, per nanogram of asbestos. Based on the above review, the validity of such a general conversion may be seriously questioned. Nonoccupational Exposures - Ambient Levels Asbestos air pollution in urban areas has been studied. Levels of chrysotile asbestos at various locations in New York City, Philadelphia, 73 pBB~000S26U Ridgev od, NJ, and Port Allegany, Pa, have been atudled by electron microscopy (Sellkoff et al, 1972). Sample sites were chosen which were distant from any known significant source of asbestos. Study results summarized in Table IV-7 show concentrations ranging from 11 to 100 nanograms/cublc meter of air (ng/m?). These authors point out that one nanogram of asbestos could represent a million chrysotlle fibrils. Ambient samples have been collected in the cities of Reading and Rochdale, England, Bochum and Dusseldorf, Germany, Prague and Pllsen, Czechoslovakia, Johannesburg, South Africa, and Reykjavik, Iceland (Holt and Young, 1973). Although no effort was made to quantitate levels, electron microscopy studies revealed the presence of chrysotlle asbestos In most samples. Results of electron microscopy studies of ambient samples In the United Kingdom are summarized in Table IV-8. Chrysotlle concentrations of 1/10 ng/m3 were observed (Richards, 1973). Asbestos levels In major US cities during 1969-1970 have been determined under contract with the US Environmental Protection Agency (Nicholson, 1971).Samples were collected on three or four different occasions for each city and analyzed by electron microscopy. Results are summarized in Table IV-9 and show that mean concentrations for the samples range from 0.7 to 24.3 ng/m3;however, 48Z of the cities had average concentrations less than 2.0 ng/m3. The highest mean, 24.3 ng/m^, was observed In Dayton, Ohio, where numerous plants processing asbestos are located. The highest concentration of 95 ng/m^ was also observed in Dayton. 74 | UB 0005262 1 Results of chrysotile measurements within buildings Insulated with asbestos and ambient levels in the vicinity of these buildings have been presented (Nicholson et al, 1975). Crysotile concentrations were determined using electron microscopy techniques as in previous studies (Sellkoff et al, 1972). Ambient levels were found to range from 0 to 46 ng/m3. Using phase contrast optical microscopy, fiber levels (ambient and indoor) were found to range from 0.000 to 0.027 fibers >5 jnn/cc, with an average of 0.006 fibers/cc. Average concentrations within the building sampled ranged from 2.5 to 200 ng/m3, indicating the possibility of fiber erosion from insulated air plenums. The same report indicates that TM S,jJ asbestos concentrations in excess of 100 ng/m-* may often be found in the - __ j t __ ' homes of asbestos workers, with the highest measured concentration being ., 5,000 ng/m3. These authors suggest that exposure in excess of 100 ng/m3 may be associated with an observable risk of asbestos disease. * Nicholson et al (1975a) published data indicating that 35 rooms in 17 office buildings in Boston, New York, Chicago, and San Francisco-Berkeley - had a mean concentration of asbestos fibers in their airs of 11,600/m^ whereas the intake airs for 15 of these buildings (all for Vhich such data .. ( V ,}' was given) contained a mean of 6,000 fibers/nr5. One room had a concentration of 102,800 fibers/m^, all the others having fiber counts below 60,000/m3. Samples of air from plenums in 11 of these buildings contained a mean concentration of 5,100 fibers/m . In an earlier report (1975b), the same investigators stated that two buildings in New York in which no asbestos was known to have been used as a fireproofing or anechoic material had a mean concentration of asbestos within their circulating airs considerably above that of the intake airs for these buildings. These 75 j BB 0005263 J findings indicate that, although pick-up of aabest a from linings applied t air-ducts and plenums may be a factor in the distribution of these fibers within buildings, these linings are not a major source of the asbestos fibers found in the air circulating within buildings. A survey carried out in the United Kingdom (Wagg, quoted by Meyer, 1976) has shown that 82Z of 73 buildings examined had airborne concentrations of asbestos fibers of up to 20,000/m^. Only 4Z had concentrations of asbestos in the range 50,000-80,000 flbers/m3. No higher c ncentratlons were reported. The higher concentrations were found in office buildings, residences, and miscellaneous types of buildings. Really high concentrations of asbestos in air (of the order of 1-100 ng/m^) have been found only within a few hundred meters downwind of asbestos processing plants (Richards and Badaml, 1971, 1973;Simecek, 1967; Meyer, 1976). Asbestos fiber levels in communities surrounding the Reserve Mining Company'8 milling operations in Silver Bay, Minnesota, have been reported by numerous investigators. Recent preliminary air sampling results have been reported for ten stations located between the Reserve Mining Company pollution source and several population centers (Fairless, 1974). Samples were collected each 6th day, beginning on November 6, 1974, (for a 1-year period). These samples were submitted blind to one or more of three laboratories where asbestos fibers concentrations were determined by electron microscopy. Results of these preliminary analyses are summarized in Table IV-10. Mean concentrations of amphibole fibers ranged from 2.6 to 8.9 x 10^ fibers/m3. In addition to amphibole fibers, chrysotile concentrations for individual samples ranged from none detected to 10.4 x 104 fibers/m^. Analyses of all samples collected have not been completed. O CO ttr LU Q K- ll- UU CJ? H- J-- OO ZZ ZZ 76 | BB 0005264 \ Concentrations of amphibole fibers hove also been reported near specific point emission sources of the Reserve Mining Company (Nicholson et al, 1974). Concentrations as high as 11 x 106 flbers/m3 of air were reported. NIOSH has performed two studies of fiber concentrations In the air of public buildings using the phase contrast microscopy counting technique (Wallingford et al* 1973; Zumwalde, 1973). Samples were collected over 6-8 hours at 7 - 10.5 liters/minute. These data are summarized In Table IV-11. Q CO Mean concentrations of 0.004 and 0.001 fibers >5 fim were observed, with the highest single concentration observed being 0.008 fiber >5 tm/cc. V-- In summary, ambient asbestos levels as determined by electron microscopy techniques are generally less than 10 ng/mP with occasional peaks as high as 100 ng/m^. Only a few studies of ambient levels have been C_2 o o CO performed using phase contrast optical microscopy. These studies indicate jilHit ambient levels to be generally less than 0.01 fibers >5 mlcc, with some peak values as high as 0.03 fibers >5 jnn/cc. >j j , I BB 0005265__1 77 REFERENCES FOR CHAPTER IV 1. Langer AM, Mackler AD, Pooley FD (1974): Electron microscopical Investigations of asbestos fibers. Environ Health Pers 9:63-80 .2 Tlmbrell V (1970): Characteristics of the VICC standard reference samples of asbestos. In Shapiro H (ed): Proceedings International Conference on Pneumoconiosis, Johannesburg. New York, Oxford University Press 3. Cook PM, Rubin JB, Maggiore CJ, Nicholson WJ (1974): X-ray diffraction and electron beam analysis of asbestiform minerals in Lake Superior waters crt 4. Rubin JB, Maggiore CJ (1974): Elemental analysis of asbestos fibers C2 by means of electron probe techniques. Environ Health Pers 9:81-84 |-- 5. Ferrell RE, Paulson GG, Walker CW (1974): Evaluation of any SEM-EDS LiJ method for identification of chrysotile. Scanning Electron Microsc Part II: 537-46 ZZ) . CP 6 Maggiore CJ, Rubin IB (1973): Optimization for a SEM x-ray CP spectormeter system for the identification and characterization of Cw ultramicroscope particles. Scanning Electron Microsc Part I: 129-36C ' 7. Langer AM, Rubin I, Selikoff IJ (1975): Electron microprobe analysis^..-, , : of asbestos bodies. Histochem Cytochem J 20:735-40 .. { .8 Dement JM, Zumwalde RD, Wallingford KM (19 75) : Asbestos fiber exposures in a hard rock gold mine. Ann N Y Acad Sci 271:345-52 9. Nicholson WJ (1974): Analysis of amphibole asbestiform fibers in municipal water supplies. Environ Health Pers 9:165-72 .10 Porter MC, Berggren RG (1974): Removal and detection of liquid borned asbestos fibers with nuclepore membrance. Pleasanton, Calif, Nuclepore Corporation, Dec. 24, 1974 .11 Beaman DR, File DM (1975) The quantitative determination of asbestos fiber concentrations. The Dow Chemical Company (unpublished report) .12 Ortiz LW, Loom BL (1974): Transfer technique for electron microscopy of membrane filter samples. Am Ind Hyg Assoc J: 423-25 13. Selikoff IJ, Nicholson WJ, Langer AM (1972): pollution. Arch Environ Health 25:1-13 Asbestos air ' J Jj 78 \ 14. Stanley HD, Norwo d RE (1974): The detection and Identification of asbestos and asbestlform minerals in talc. In Proceedings of the Burea of Mines Talc Symposium, Washington, D C 15. Rohl AN, tanger AM (1974): Identification and quantitation of asbestos in talc. Environ Health Pers 9:95-109 16. Crable JV, Knott MJ (1968): Application of x-ray diffraction analysis of crocidolite and amoslte in bulk or settled dust samples. Am Ind Hyg J 27:383-85 17. Crable JV, Knott MJ (1966): Quantitative determination of chrysotile amosite and crocidolite by x-ray diffraction. Am Ind Hyg J 27: 44953 18. Keenan RG, Lynch JR(1970):Techniques for the detection, identi- ,r" ;V` fication and analysis of fibers. Am Ind Hyg J 31:587-97 ; ,j 19. Birks LS, Fatemi M, Gilfrich JV, Johnson ET (1975): Quantitative analysis of airborned asbestos by x-ray diffraction: Feasibility study AD-A00753Q, Naval Res Lab, Washington, DC ' 20. Schlez JF (1974): The detection of chrysotile asbestos at low levels C in talc by differential thermal analysis. Thermochemica Acta 8:197- r!' v . 203 *- . * 21. Julian Y, McCrone WC (1970): Identification ofasbestos fibers by - microscopical dispersion staining. Microscope 18:1-10 ' 22. McCrone WC, Stewart IM (1974): Asbestos. American Laboratory, April ^ ' o c? 23. US Dept of Labor, Occupational Safety and Health Administration (1975): Occupational Safety and Health Standards. Fed Reg 29 CFR 1910.1001, 1975 24. Corn M, Sansone EC (1974): Determination of total suspended particulate matter and airborne fiber concentrations at three fibrous glass manufacturing facilities. Environ Res 8:37-52 25. Leidel NA, Busch KA (1974) : An evlauation of phase contrast micro scopes for asbestos counting. Presented at the 1974 American Industrial Hygiene Conference, Miami Beach, Florida, May 18, 1974 26. Conway RE, Holland WD (1973): Statistical evaluation of the procedures for counting asbestos fibers on membrane filters. LFE Corp., Richmond, CA. Prepared for Asbestos Information Association/North America, New York, 1973 27. Rajhans GS, Bragg GM (1975): A statistical analysis of asbestos fiber counting in the laboratory and industrial environment. Am Ind Hyg Assoc J 36:909-15 J BB 0005267 | 79 28. Leidel AL* Bayer SG, Zumwalde RD (1975): SUPHS/NIOSH Membrane Filter Method for Evaluating Airborne Asbestos Fibers. US Dept Health* Education* and Welfare* Public Health Service* Center for Disease Control* National Institute for Occupational Safety and Health* November 1975 (In print) 29. Lynch JL* Ayer HE (1966): Measurement of asbestos dust exposure In the asbestos textile industry. Am Ind Hyg Assoc J 27:43-37 30. Lynch JL, Ayer HE, Johnson DL (1970): The interrelationships of selected asbestos exposed indices. Am Ind Hyg Assoc J 31:598-604 31. Nicholson WJ, Rohl AN* Welsman I (1975a): Asbestos Contamination of the air in public buildings. Final report to the Environmental Protection Agency, Contract No. 68-02-1346 32. Nicholson, WJ (1973): Testimony, United States versus Reserve Mining Company, No. 5-72-Civil~19, Sept. 6, 1973. Exhibit No. 62. y-x 33. Bruckman L, and Burino R (1975): Asbestos--Rationale behind a proposed air quality standard. J Air Pollut Control Assoc 25: 12 (- 34. Holt PF, Young DK (1973): Asbestos fibers in the air of towns. ; Atmos Environ 7:481-83 r 35. Richards AL (1973): Estimation of submlcrogram quantities of chrysotile asbestos by electron microscopy. Anal Chem 45: 809-11 .- 36. Nicholson WJ (1971): Measurement of asbestos in ambient air. Final report to the Environmental Protection Agency, Contract EPA 70-92 37. Fairless B (1974): Asbestos fiber concentrations in air samples , taken from areas near the western arm of Lak Superior, Progress Report, US Environmental Protection Agency Region V, Chicago* Illinois. m"7" 38. Nicholson W (1973): U.S. District Court for Minnesota. United States versus Reserve Mining Company.No. 5-72-Civll-19, Sept. 6, Exhibit No. 62 39. Wallingford KM, Bierbaum PJ, Dement JM (1973): Determination of asbestos levels in a public building located in Towson, Maryland, EIB, DFSCI, NI0SH 40. Zumwalde, R.D. (1973): Asbestos survey of Federal Office Building #7, U.S. Court of Claims and Court of Customs and Patent Appeals Building, Washington, D.C. and George H. Fallon, Office Building, Baltimore, Maryland EIB, DFSCI, NIOSH GG I'335 80 | BB 0005268^2 41. Nicholson WJ, Rohl AN, Weisman I (1975b): Asbest a Contaminati n f Building Air Supply Systems. Paper given at Las Vegas, Nevada, 14-19 September, 1975 42. Meyer PD (1976): Sampling and Detection of Asbestos in Air, Food, Soil and Water. Paper prepared by RVO TNO for European Economic Community, 1976 43. Richards AL, Badaml DV (1971): Chrysotlle Asbestos in Urban Air. Nature 243:93-94 44. Simecek J (1967): Measuring Asbestos Dust. Staub - Reinhalt Luft 27:20-23 i.:\,-n 1 '$ ' f-r\ iLtO bVo \ 81  TABLE IV-1 TYPICAL OPTICAL DATA FOR ASBESTOS MINERALS Asbestos Type Crystal System Refractive Indices Extinction Angles Chrysotile Anthophyllite Amosite Crocidollte Tremolite** Actinolite ** 4 monoclinic orthorhombic monoclinic II II II 1.49-1.57 1.60-1.66 1.66-1.70 1.69-1.71 1.60-1.65 1.62-1.68 yAL* = 0 yAL * 0 yAL - 14-21 yAL 3-15 yAL - 10-21 yAL * 10-15 *L = long direction of fibers ** Tremolite and actinolite form a continuous mlneralogical series. Values shown are for end members. Sign of Elongation + 4* + -- + + TABLE IV-2 DISPERSION STAINING COLORS FOR ASBESTOS MINERALS USING PLANE POLARIZED LIGHT Asbestos Type Chrysotile Anthophyllite Amosite Crocidolite Refractive Index Liquid 1.560 1.610 1.670 1.700 Dispersion Staining Colors light blue blue-green red magenta magenta magenta golden yellow II blue magenta GG 1*39? Bb" 000527 0^2 6 TABLE IV-3 THEORETICAL MINIMUM DETECTABLE FIBER CONCENTRATIONS BY PHASE CONTRAST OPTICAL MICROSCOPY Sampling Period (Minutes) Minimum Detectable Cone, fibers >5 pm/ec 15 0.04 30 0.02 60 0.01 90 0.007 120 0.005 240 0.003 480 0.001 *Based on a sample flow rate of 2.01 1pm and a microscope counting field area of 0.0071 mm^. TABLE IV-4 -- -- d J ( | ^ NV DID! ' ' "^1 NO" V 3 * * S" l \J `i rrJ HLES ASBESTOS COUNT/WEIGHT RELATIONSHIPS FOR ASBESTOS TEXTILE PLANTS Type Count By Phase Contrast Microscopy Fibers per Nanogram of Asbestos Total Fibers 11 >5 ym Fibers 5 From Lynch and Ayer (1966) 83 I BB 0005271 | TABLE IV-5 ASBESTOS COUNT/WEIGHT RELATIONSHIPS FOR VARIOUS INDUSTRIAL OPERATIONS Product Type Fiber Count Geometric Mean Fibers/ng Geometric Standard Deviation Textile Total >5 pm Friction Total >5 pi Pipe Total ^5 fjm From Lynch and Ayer (1966) 14.5 6.7 26.3 13.9 46.5 22.5 2.5 3.3 3.4 3.6 2.8 2.9 TABLE IV-6 P6 ^ < - I. ..;*! j\0 NOT COME FROM PPG FILES SUMMARY OF FIBER COUNT/MASS RELATIONSHIPS Analysis Method Average Cone, (range) Total Fibers by Electron Microscopy 4.82 (0.66 - 11.79) Asbestos Mass by Electron Microscopy 3,900 (540 - 9600) Fibers >5 pan by Optical Microscopy 1.51 (0.16 - 2.8) Approximate Relationships: 1 ng * 1,200 total fibers by electron microscopy 1 g * 400 fibers >5 pan in length by phase contrast microscopy From Dement et al (1975) 84 Units of Measure fibers/cc ng/m3 fibers/cc GG \m I BB 0005272^1 TABLE IV-7 SUMMARY OF AMBIENT ASBESTOS LEVELS IN VARIOUS CITIES Sample Site Asbestos Cone. 10"9 gm/n>3 New York City Manhattan Bronx Queens Staten Island Philadelphia, Pa. Ridgewood, N.J. Port Allegany, Pa. 25-60 25-28 19-22 18-29 11-21 45-100 20 10-30 From Selikoff et al (1972) TABLE IV-8 ;'i j; ,,, , Old u' ~ ' ' ' V ) 3 J | l:l LtS SUMMARY OF AMBIENT CHRYS0TILE LEVELS IN THE UNITED KINGDOM Sample Site Rochdale (Factory Grounds) Rochdale (Town Center) Lancashire/Yorkshire Industrial Site (Oldbury) From Richards (1973) Chrysotile Cone. 10-9 gm/m3 1-10 10 1-10 10 85 !-B 0005273"7 TABLE 17-9 SUMMARY OF AMBIENT ASBESTOS LEVELS IN 49 CITIES FOR 1969-1970 Cone. 10^ gm/m3 Cumulative % of City Mean Cone. < Given Cone. ~ 0.1-1.9 1.0-1.9 2.0-2.9 3.0-3.9 94.0-4.9 5.0-5.9 >6.0* 12 48 64 72 86 94 6Z ^Highest Mean - 24.3 ng/m^ observed in Dayton, Ohio SUMMARY OF AMPHIBOLE FIBER CONCENTRATIONS FOR TEN SAMPLE SITES IN THE VICINITY OF RESERVE MINING Sample Site Amphibole Cone. 10"9fibers/m^ Mean Range Duluth Duluth (Residence) Silver Day (Residence) Babbit (Residence) Hoyt Lake Hibbing Cloquet Pengilly Virginia Mt. Iron Overall Mean - 7.6 X 10~yfibers/3 From Fairless (1974) 7.5 2.6 11 13 8.5 5.6 6.8 6.6 4.2 8.9 86 0-17 0- 8 0-30 0-82 0-31 0.19 0-30 0-17 0-12 0-45 BB 0005274 l r. ! TABLE IV-11 SUMMARY OF FIBER CONCENTRATION DETERMINATIONS IN THE AIR OF PUBLIC BUILDINGS USING PHASE CONTRAST OPTICAL MICROSCOPY Building Location Fibers >5 /an in Length/cc Mean and Range Baltimore, Maryland and Washington, D.C. Towson, Maryland 0.004 (0.001-0.008) 0.001 (0.000-0.003) From Wallingford et al (1973) and Zumwalde (1973) 1c . 1* i f>.it nil J_BB_0005275~y 87 Cr M4f;2 V. BASIS FOR THE RECOMMENDED STANDARD The first modern approach to the setting of an asbestos standard was proposed by the British Occupational Hygiene Society (BOHS 1968) in terms of fiber concentration. In 1968, a subcommittee of the Society evaluated data on 290 men at work in an asbestos factory. These data were provided by company sources. All the men had been employed after January 1933, following implementation of dust control measures mandated by the Factory Inspectorate in 1931. Estimates of the fiber exposure of these workmen were also provided by the company. Of the 290 individuals, 8 were stated to have x-ray evidence of asbestos disease and 16 had rales. Noteworthy in the 1968 data was the preponderance of individuals who had been employed less than 20 years. Only 118 of the 290 persons had worked for longer than 20 years and a scant 13 has been employed for 30 or more years. After a review of these data, the BOHS proposed a standard which was adopted with minor modifications by the British government in 1969, and implemented in May 1970. All fibers between 5 and 100 microns in length were counted by light microscopy. The standard required no action to be taken below 2 fibers/cc. Between 2 fibers/cc and 12 fibers/cc, control measures commensurate with the exposure circumstances (time and frequency of worker exposure) were prescribed; above 12 fibers/cc, full application of control measures, including respiratory protection, was mandatory. The BOHS predicted that the risk of being affected, to the extent of having the earliest clinical signs of asbestos exposure (rales), would be less than 1% for an accumulated exposure of 100 fiber-years/cc (2 fibers/cc for 50 Bb" 0Q05276_! 88 years, 4 fibers/cc for 25, etc). Data (Lewinsohn, 1972) from the same factory which formed the basis for the BOHS standard demonstrate that a greater prevalence of abnormalities now exist (Table V-l). These data, in addition to demonstrating a dose-response relationship for radiographically detected abnormalities consistent with asbestosis, further showed a 17Z prevalence of abnormal radiographic findings (6Z consistent with asbestosis) in individuals employed since 1950. Weill et al (1975), when considering lung function and irregular small opacities, reported that there was little evidence of a dose-response relationship below 100 mppcf-years. They further concluded that a concentration of 5 fibers/cc could be cautiously considered as "safe". Ayer and Berg (1976), however, reported data which suggest that the BOHS GO LU --J U_ CD a_ standard, of an average cumulative exposure of 100 fiber-years/cc, for chrysotile asbestos may prevent significant decreases in pulmonary function only when combined with periodic spirometry and further reduction of exposure for affected workers. Holmes (1973) has since stated that the o CD data upon which the BOHS standard was based were Inadequate to set a K- - standard to prevent asbestosis. The BOHS-recommended standard of 2 fibers/cc was based on data related only to asbestosis and the Society clearly cautioned that, since a quantitative relationship between asbestos exposure and cancer risk was not known, it was not possible at that time to specify an air concentration which was known to be free of increased cancer risk. (BOHS 1968) Howard et al (1976), in a follow-up examination of the textile workers previously studied by Doll (1955) and Knox et al (1965, 1968) for cancer, and by Lewinsohn (1972) for asbestosis, reported a statistically fiTjwilllJ-. 89 '"cc IM4 significant increase in the risk of developing lung cancer (1.8 tinea th expected) among those first entering scheduled areas from 1933 to 1950. In the same study, they also reported an excess of deaths due to lung cancer (1.9 times the expected) after 15 or more years from initial exposure among those who started work subsequent to 1950, a period of improved industrial engineering control technology and regulation. In a study of miners exposed to amphlbole fibers (amoslte) in the cummingtonite-grunerite ore series, with airborne concentrations of less ^ ( than 2.0 fibers/cc (average concentration, 0.25 fibers/cc) and 94Z of the CHS . fibers shorter than 5 fm in length, Glllam et al (1976) have demonstrated threefoldJ increases inJ _____________________ th__e__ ris_k1_s___ o_f mortality from1 both malignant and___J j.** _______________J_________________________________ __ J Z-FZ UJ nonmalignant respiratory diseases. Newhouse (1969, 1973) and Newhouse et al (1972) have shown that the cancer risk to factory workers following mixed exposure to chrysotile, amoslte, and crocidollte is dose-related. The women reported to have heavier exposures (as judged by their occupations) showed a sixfold excess of cancer following only 15 years' latency, whereas those with moderate or low exposures required 25 years' latency to demonstrate an excess. The rate of mesothelioma increased with both the severity and the length of exposure. However, even with as little as two years of asbestos exposure, six mesotheliomas occurred among female employees. McDonald (1973) stated that the risk of developing lung cancer was essentially confined to persons with a dust index above 200 mppcf-years, and Enterline et al (1973) showed no direct dose-response for respiratory cancer below 125 mppcf-years. In a review of these two papers, Schneiderman (1974) concluded that, instead of being consistent with a 90 threshold level at which no cancer risk exists, these data did not provide evidence for a threshold or for a "safe" level of exposure. He pointed out that In the paper by Enterline et al (1973) there Is no dose group for which the Standardized Mortality Ratio (SMR) is below 100 (100 normal), but that the 95Z confidence limits on the SMR's included 100 for two of the three dose groups below 125 mppcf-years. One of the dose groups (25-62.4) had a statistically significant excess mortality from lung cancer, whereas for the other two this mortality rate was insignificantly elevated above the expected values. Regarding McDonald's paper, Schnelderman stated that o crtj} O 'tj it is hard to determine what is excess since no expected numbers for each 73 group were given upon which to base this comparison. Among amoslte workers with employment of 3 months or less, Selikoff (1976) reported excess cancer risks of 3.87, 1.68, .and 1.65 times those expected for cancer of the lung, colon and rectum, and all sites, j respectively. Anderson et al (1976) have reported a significant excess of >o radiographic abnormalities of the chest characteristic of asbestos exposure (pleural and/or parenchymal) 25 - 30 years after the onset of household contamination. These abnormalities were observed in 35Z of 326 otherwise healthy workers who had household contacts with amoslte asbestos. In addition, four pleural mesotheliomas were found in this group. 91 | BB 0005279 | T VI. THE RECOMMENDED STANDARD Available studies provide conclusive evidence that exposure to asbestos fibers causes cancer and asbestosis in man. Lung cancers and asbestosis have occurred following exposure to chrysotile, crocidolite, amosite, and anthophyllite. Mesotheliomas, lung and gastrointestinal cancers have been shown to be excessive in occupationally exposed persons, while mesotheliomas have developed also in individuals living in the O </S ' - ...w neighborhood of asbestos factories and near crocidolite deposits, and in persons living with asbestos workers. Asbestosis has been identified among persons living near anthophyllite deposits. Likewise, all commercial forms of asbestos are carcinogenic in rats, producing lung carcinomas and mesotheliomas following their inhalation, and mesotheliomas after intrapleural or ip injection. Mesotheliomas and lung cancers were induced following even 1 day's exposure by inhalation. The size and shape of the fibers are important factors; fibers less than 0.5 im in diameter are most active in producing tumors. Other fibers of a similar size, including glass fibers, can also produce mesotheliomas following intrapleural or ip Injection. There are data that show that the lower the exposure, the lower the risk of developing cancer. Excessive cancer risks have been demonstrated at all fiber concentrations studied to date. Evaluation of all available human data provides no evidence for a threshold or for a "safe" level of asbestos exposure. GG V-W TiT 0005280_i In view of the above, the standard should be set at the lowest level detectable by available analytical techniques, an approach consistent with NIOSH's most recent recommendations for other carcinogens (le, arsenic and vinyl chloride). Such a standard should also prevent the development of asbestosls. Since phase contrast microscopy is the only generally available and practical analytical technique at the present time, this level is defined as 100,000 fibers >5 pm in length/m3 (0.1 fibers/cc), on an 8-hour-TWA basis with peak concentrations not exceeding 500,000 fibers >5 pm in length/m^ (0.5 fibers/cc) based on a 15-minute sample period. Sampling and c:. TMj o analytical techniques should be performed as specified by NIOSH publication USPHS/NI0SH Membrane Filter Method for Evaluating Airborne Asbestos Fibers - T.R. 84 (1976). c This recommended standard of 100,000 fibers >5 pm in length/m^ is Intended to (1) protect against the noncarcinogenic effects of asbestos, (2) materially reduce the risk of asbestos-induced cancer (only a ban can L ' 3 assure protection against carcinogenic effects of asbestos) and (3) be measured by techniques that are valid, reproducible, and available to Industry and official agencies. However, some difficulties arise in that specific work practices and innovative engineering control or process changes are needed. But because of the well-documented human carcinogenicity from all forms of asbestos, these difficulties should not be cited as cause for permitting continued exposure to asbestos at concentrations above 100,000 fibers >5 pm in length/m 3, 93 BB 00 052in_2 This standard was n t designed for the p pulation-at-large, and any extrapolation beyond general occupational exposures is not warranted. The standard was designed only for the processing, manufacturing, and use of asbestos and asbestos-containing products as applicable under the Occupational Safety and Health Act of 1970. j n \J i 0^ J i - * GG M,4i;9 94 I BB 0005232 I REFERENCES FOR CHAPTERS V AND VI 1969 Standard for asbestos dust concentration for use with the asbestos regulations. Department of Employment and Productivity, Her Majesty's Factory Inspectorate. Technical Note 13, 1970 Lewinsohn HC (1972): The medical surveillance of asbestos workers. Soc Health 92:69 Weill H, Zlskind MM, Waggenspack C, Possiter CE (1975): Lung function consequences of dust exposure In asbestos cement manufacturing plants. Arch Environ Health 30:248-52 Ayer H, Berg J (1976): Cumulative asbestos exposure and forced vital capacity. Submitted for publication to Arch Environ Health Holmes S (1973): Environmental data in industry, in Bogovski P, Timbrell V. Gilson JC, Wagner JC (eds): Proceedings of the Conference on Biological Effects of Asbestos. Lyon, pp 135 O -.... ICSS `` t ' ***** Newhouse ML (1969): A study of the mortality of workers in an asbestos factory. Br J Ind Med 26:294 Newhouse ML (1973): Cancer among workers in the asbestos textile industry, in Bogovski P, Gilson JC, Timbrell V, Wagner JC (eds): Proceedings of the Conference on Biological Effects of Asbestos. Lyon, pp 203 Newhouse ML, Berry G, Wagner JC, Turok ME (1972): A study of the mortality of female asbestos workers. Br J Ind Med 29:134 Howard S, Kimben LJ, Lewinsohn HC, Peto J, Doll R (1976); A Mortality Study among Workers in an Englosh Asbestos Factory. Oxford University, (in press) .J fC-aw 'rlar u Doll R (1955): Mortality from lung cancer in asbestos workers. Br J Ind Med 12:81-86 Knox JF, Doll RS, Hill ID (1965): Cohort analysis of changes in incidence of bronchial carcinoma in a textile asbestos factory. Am NY Acad Sci 132:526-35 Knox JF, Holms S, Doll R, Hill ID (1968) : Mortality from lung cancer and other causes among workers in an asbestos textile factory. Br J Ind Med 25:293-303 Gillam JD, Dement JM, Lemen RA, Wagoner JK, Archer VE, Beljer HP (1976): Mortality patterns among hard rock gold miners exposed to an asbestiform mineral. Ann NY Acad Sci 271:336-44 95 | BB 0005233 J TABLE VI-1 B.O.H.S. ASBESTOS STANDARD X-RAY FINDINGS IN AN ASBESTOS TEXTILE FACTORY * DECEMBER 1970 (MALES) X-ray Findings Years of Exposure No. Pleural Pulmonary Normal Fibrosis* Fibrosis 0-9 10 - 19 20 - 29 30-39 40 - 49 613 548 189 122 114 51 42 9 12 2 10 0 18 20 30 21 17 17 63 * Consistent with asbestos exposure **Including changes not considered due to asbestos exposure Adapted from reference 2 Total Abnormal** 65(11%) 67(36%) 63(55%) 33(78%) 10(83%) # ftlsAinT NOT QQUt irKoivi i U7 ^ i H ff tTlS"-"--- vv U. S. S0nWMT PIHniNS OfflO; 1977-757-057/6705 Region No. 5-11