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r /9S^^7Z>.S Editorial British Journal ofIndustrial Medicine 1989:46:681 -682^?>i, H Comparing biological effects of mineral fibres 70p. ' Careful examination of the great majority of in vitro mental Protection Agency maintain that chrysotile Hits and in vivo experimental protocols to assess the the same potential as the other asbestos fibre types, biological elfects of mineral fibres shows that com and that manmade mineral fibres have lower patho parison of the effects (in vitro cytotoxicity, fibrogen- genic potential based on animal experiments using icity, and tumour yield) has traditionally been based equal mass doses. on a gravimetric basis--that is, by comparing the Limited attempts to transform retrospectively effects produced by equal mass oftested minerals--for gravimetric doses into fibre number-doses have example, 50 /xg/105 cells; 20 mg dose by intraperi- indicated that if based on fibre number the patho toneal injection; 20 mg/m3 by inhalation, etc). genicity would show that "fibre for fibre" chrysotile The effects reported are often not consistent with would be seen as less potent than the other asbestos epidemiological observations. In recent years the fibre types, and possibly some other manmade mineral development-of sophisticated techniques for tissue fibres as well. For instance, Davis et al have reported mineral analysis has led to some possible explanations that rats submitted to dust clouds of chrysotile, for the inconsistencies between animal experimental crocidolite, and amosite showed more lung fibrosis data and epidemiological evidence, pointing to the and tumours after inhalation of chrysotile than with different durability of mineral fibres and their dif either amphiboles.3 But, they state: "... it was found ferent relative lifespan persistence between laboratory that the chrysotile dust clouds used in this study animals and man. contained many more fibres longer than 20 microns We consider that another explanation may also than either of the amphibole dust clouds." reside in the basis for reporting the observed effects-- In 1986, Peto, using animal data from Wagner,* that is, equal mass v equal number of fibres. analysed the effects per fibre rather than per unit mass Contrary to experimental data, human experience relevant to the comparison of asbestos and manmade of exposure to different asbestos fibre types and mineral fibres in the induction of pulmonary tumours manmade mineral fibres has shown an impressive by inhalation. The results shown in the table indicate difference in pathological potency, chrysotile being that a similar mass of chrysotile produced a greater much less fibrogenic and carcinogenic, and having incidence of tumour than manmade mineral fibres but little mesothelioma producing potential (if at all) that the risk per fibre may have been similar for compared with amphiboles. Recently, Wagner et al chrysotile and glass wool, and possibly greater for wrote, "We believe therefore that chrysotile is the least rock wool. (All groups had been exposed to 10 mg/m3 harmful form of asbestos in every respect and that but the fibre count was more than 10 times higher for more emphasis should be laid on different biological chrysotile than for rock wool or glass wool.) While effects of amphibole and serpentine asbestos fibre."1 there is some scepticism in the scientific community Recently, manmade mineral fibres, especially rock/ about such retrospective analysis, it would be most slag wools, have been positively correlated with excess desirable to have more relevant experimental data. incidence of lung cancer in production workers at low Also in 1986 Goldsmith indicated that "based on exposure levels, indeed at exposure levels (~ 1 f/ml) fibre or particle counts, manmade mineral fibres where chrysotile has been shown to produce no excess appear to be more potent than asbestos with regard to lung cancer. There is some uncertainty about the chronic pulmonary disease."5 . estimates ofexposure in the early production phase of Finally, in a more recently published in vitro study rock/slag, and there may have been additional con on the comparison of mass v number of fibres in the tributing factors such as the presence of polycyclic cytotoxic response of Chinese hamster lung V79 cells aromatic hydrocarbons or arsenic to die reported to erionite, crocidolite, and chrysotile, especially for excess lung cancer mortality; all these sources may fibres L >8 microns, W <0-25 microns, the UICC have contributed to the observed hazard, but as Doll chrysotile fibres emerge as the least potent.6 Their data said at the 1986 Copenhagen Symposium "... none show that both samples of erionite required fewer has produced a quantitatively similar hazard else fibres than UICC crocidolite, and that UICC where, unless exposure was both intense and pro chrysotile required a significantly higher number of longed."2 fibres than the other three tested materials to produce The problem is that despite the human data, some similar cytotoxicity. For instance, the LD values (in regulatory agencies such as the United States Environ fibre number) for V79 cytotoxicity shows the follow- K. t * # 681 HWBUI0000940 682 Lung tumour distribution related to cumulative dosage Material (no ofrats) BAH* (a) Adenomaf (b) Adenoma% (c) Adeno carcinoma (d) AU neoplasms (b + c + d) Average^ cumulative doseper rat at 12 months Tumours per 100fibres)an3 *h UICC chrysotile (48) 50 1 11 12 Glass microfibre (48) 30 0 11 Rock wool (48) ll l 02 Glass wool with resin (48) 3 0 0 11 Glass wool resin free (47) 1 1 0 01 Controls (48) l0 0 00 656 18 223 0-4 39 5 1 55 18 41 2-4 ---- 'Bronchoalveolar hyperplasia, tBenign. (Some features of malignancy. Fibres/cm'. Note: This table is reproduced from "Request from HSE for an opinion on the carcinogenic potential ofglass fibre, glass wool, slag wool and rock wool. A resume of the revelant biological properties" which was prepared for the Committee on carcinogenicity. ing: erionite samples: 'l l x 10s; crocidolite: 6-28 x IQ5; chrysotile: 348-8 x 103. For fibre lengths equal to or smaller than 5 microns the difference is even more pronounced. These observations do not rule out other important factors in possible reasons for a gradient in fibre potency, such as chemical differen ces in fibre types, durability (persistence in tissues), and possibly others. Fora similar mass, a sample with a higher number of fibres would also have a larger surface area than a sample with lower fibre number. At present, TLVs for asbestos fibre types are in fibre numbers almost everywhere, whereas gravimetric standards (from '5 to 10 mg/m3) are still the current rule for manmade mineral fibres in many countries, although some national regulatory authorities have recently adopted standards in fibre numbers. Thus it will be interesting to follow up the developments and to watch how TLVs for manmade mineral fibres will eventually compare with each asbestos fibre type. Meanwhile, carefully planned animal experimenta tion, where doses are measured in fibre numbers, and where results are expressed in effects//fibre number, would certainly help to support the contention that if chrysotile must be controlled to low levels such as 1 f/ml, manmade mineral fibres must also be con trolled at the same levels (and possibly lower levels in the case of rock wool). The manmade mineral fibres, as well as the refractory (ceramic) fibres, are used/ proposed as asbestos substitutes in many applications including friction materials, thermal insulation, fibre reinforced plastics and resins, and gaskets and joints. Currentstatus ofregulation formanmade mineral fibres Regulations governing exposure to manmade mineral fibres in many countries are still based on gravimetric measurements, from '3 to 10 mg/m3. Sweden and Poland, however, have now turned to fibre number (2-0 f/ml), and Denmark, Norway, and Sweden are considering a TLV of 1-0 f/ml. Superfine manmade mineral fibres are classified as a "suspected carcino gen" by Austria and the USSR, and are strictly regulated in the United Kingdom with a TLV of I 0 f/ml. In the United States the Occupational Safety and Health Administration is considering a recom mendation of3 f/ml made by the National Institute for Occupational Safety and Health. Methods for fibre counts are already available. The ISO has published a proposed method (Determination of the number of airborne inorganic fibres by phase contrast optical microscopy-membrane filter method) which is expec ted to be officially adopted in 1989 or 1990.' The WHO/Regional Office for Europe/Copenhagen has also published a reference method for measuring airborne manmade mineral fibres.* It seems therefore that the stage is set for an increasing trend away from gravimetric data to fibre counts, and that if TLVs are to be expressed in fibre numbers per unit volume of air such TLVs should be based on scientific data which are reported on the basis of fibre number rather than on a mass basis. Science Faculty, University ofSherbrooke, Sherbrooke, Quebec, Canada J1K2R1. jdunnigan References 1 Wagner iC, Newhouie ML, Cornu B, Rossitcr CER, Griffiths DM. Correlation between fibre content ofthe lung and disease in East London asbestos factory workers. Br J Ind Med 1988;45:305-8. 2 Doll R. Manmade mineral fibres in the working environment. Proceedings of international symposium. Arm Occup Hyg 1987;31:805-17. 3 Davis IMG, Beckett ST, Bolton RE, Collings P, Middleton AP. Mam and number of fibres in the pathogenesis of asbestosrelated disease in rats. Br J Cancer 1978;37:673-88. 4 Wagner JC. Health hazards of substitutes. In: Proceedings of the world symposium on asbestos, Montreal. 1982. Montreal: Canadian Asbestos Information Center, 1932:244-66. 5 Goldsmith JR. Comparative epidemiology of men exposed to asbestos and man-made mineral fibers. Am J lnd Med 1986:10:543-32. 6 Palckar LD, Most BM, Coffin DL Significance of mass and number of fibers in the correlation of V79 cytotoxicity with tumorigenic potential of mineral fibers. Environ Res 1988;46:142-52. 7 International Organisation for Standardisation. Determination of ihe number concentration of airborne inorganic fibres by phase contrast optical microscopy-membrane filter method. Geneva: ISO, 1986. [Doc ISO OP8672fWP5.) 8 World Health Organisation. Reference method for measuring airborne man-made mineral fibres. Copenhagen: WHO 1985. (HE4.) 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