Document XOzNZN4Bm0Bp5O7B0x87Xo62x

-.V ' * ALLOYS 111VJ SION OP UNION CARBIDE LIMITED *fiC/ve0l . Can i7 mQ . PRC: jrrrw y cjnai-ton sthkut London w.i. MAY PA I It HIOO ' CAflt.ES: VNICAflUIDE IOMDUS W.i, - TELEX Zi~0^ Dr. A.E. Pufahl, Assistant General Manager, Asbestos, Union Carbide Corporation, Minins & Metals Division, 270 Park Avenue, New York, N.Y. 10017, U.S.A. 12th January, 1966. Dear Dr. Pufahl, . You will recall that from time to time we have sent you extracts from publications which indicate concern felt in industry on the detrimental effect asbestos has on health. We tried to obtain some information for Southalls Paper Mills, who wanted to use our asbestos In a sanitary tissue of the internal type. They were concerned about possible danger to health. We were unsuccessful then in obtaining answers to their specific quest ions, arid could only deal with them in vay* general terms. However, 1 fool that we may now be able to be more specific when tho occasion arises by using the information contained in the documents, British Industrial Biological Research Association and Report of Proceedings of an International Conference on the Biological Effect of Asbestos, copies of which we enclose with this letter. ' We believe the documents are well worth having studied by the Medical Advisei1 to the Corporation, and it is our belief that we may well be able to take advantage of the fact that our material supposedly contains so little oil the dangerous trace elements that are mentioned in those documents. If this is so, then we certainly have good copy for publicity use. You will be iutorou bod to no te that 'two American medical authoritiers attended the International Conference, namely Dr. II.E. Ayer, PubLle Health Service, Cincinnati!, and Dr. I.J. Uellkoff, Mount Sinai Hospital, New York. We would appreciate your comments and conclusions in due course. , P.R. Cheston Assistant Sales Manager c.o. Mr. II. Relchard.t"Mr. T _ TVmonfiV'm Tivi JTl T tt~ii ** "" - 407059 - UCC 020758 ., / .< . ><: it ><C, I /-) (- tej- i <C / vVV,y. /t <w.t ^-ityy-if'l-L'l i'Zi f -hat the silicons fluid is devoid of silica granules. [The intense fibrous tissuo reaction and, the pros-.a so of doubly rofractilc crystals in the lesions described by V/inor c~; ai. (loc.nt-:.) have not been reported by other workers using pure liquid c.r-soi id qjliconos. Two of the throe silicone preparations, referred to by V/inor t (locjnvt.) contained animal end vegetable fatty acids, both of watch are capable of inducing' in their own right the severe granulomatous reaction observed. It is quite probable that a significant or over, major role was played by the fatty acids in the induction of the reported savers fibrous lesicr.s. If we are to believe the claim of the existence of silica granules in the silicone fluid preparation, then it is conceivable that the silica ray have boon a contributory factor in the production of the tissue reaction. However, a very reliable source of ours had no hesitation in refuting the claim that silicone fluid is contaminated with silica. Only under conditions of extremely high temperatures and high pressures and in the presence of oxygen is oxidation of silicone fluid to silica possible. For this reaction to proceed during shelf storage is not only highly improbable but well-nigh impossible,] MESOTHELIOMA AMD ASBESTOS The development of tumours (mesothelioma) following exposure to , asbestos dust tends to be insidious (SI3RA Bull. 1965, A, 31 i)- The initial obstacle to recognition of the hazard lay in correlating two episodes -- exposure to asbestos dust, however light, and subsequent - development of the tumour. Once this connexion had been established the problem assumed new and somewhat alarming dimensions since the time-lag between causa and effect rap* well extend to over half a century. Before '950 the industrial and commercial importance of asbestos in this country was still relatively small. Thus it is only now that the _ ir.oidenco of diffuse pleural or peritoneal mesothelioma can be expected to show a steady upward trend- This pattern is becoming all toe apparent. Public interost in tha problem should certainly have been alerted by a report in the Sunday Times (jl October 1S>5) on the work cf Howhouso b. Thompson (3r. .T. ind. Med. 1965, 22, 26l). Their important epidemio logical study covered *1) patients (41 mains and h2 fcunlos} with positively diagnosed diffuse pleural or peritoneal mesothelioma admit ted so the London Hospital ovor the c our so of approximately 30 yr. Hvidcr.ce of exposure to asbestos was obtained in qo of tha ?6 cases whose background histories could bo traced with relative accuracy. Of the remaining 56, 11 had lived within half a mile of an asbestos factory. In a control group of 76 in-patients, matched for-sex and age, only 14 gave histories of previous direct or domiciliary exposure to "asbestos. The rise in reported cases of asbestos bodies in the lungs may reflect either an absolute increase in. incidence or the results of more searching pathological examinations in the light of this new knowledge. 3a that as it cay, Cauna et al. (a. Am. med. Ass. 1965, 192, 571) report a 415^ incidence of asbestos bodies seen in the courso of 100 routine adult autopsies (47? in malac; 34J in females), although nono were found before the ago of 24- Ho cases of nosotholioma or aaboatoais could bo identified and primary cancor of the lung vac only proaont in two patients --one with aaboatoo bodies and ono without. The authorc draw attention to ! * ' , . ' A0706C -515 the problem of positive identification of the asbestos body and the differentiation between it and the similar structure encountered in .taloosio. They believe that the problem is cade acre difficult because of the similarity betveen asbostosis arising from exposure to treaiolite but the method used in the present study was electron-probe analysis. Nonetheless, the authors rejected findings which did not positively identify classical asbestos bodies and still produced an incidence much high'*r than-previous studies had revealed at autopsy, notably 2'j.d/o in October 1564). Preach workers have also drawn attention to the problem, and an analysis of histopsthological findings has been published (Turiaf et al. Prcsse raid. '965 12.' 2199)- Although the asbestos industry in that country is not large,- the incidence of mesothelioma is rising and concern is understandable. Recording the incidence of asbestosis and mesothelioma and standardising diagnostic techniques famed part of the terms of reference of the Vorki- j Croup convened, under the auspices of the Geographical Pathology Committee of the International Union against Cancer (I.tf.C.C.), to look into the whole question of asbestos and cancer. The comprehensive report of the Group (fr. J. lnd. Ked. 1965i 22, i65) recommends three main lines of attach: Bpideniologicc.l -- more information, is required concerning the results of exposure to particular typos of asbestos fibre (amocito, crocidolite, anthophyllite, chrycotila or tremolito} by inter- and intranational studies in specified areas. It is recommended that studies be undertaken into the relation betveen du3t dosage, the physical state of the dust and the incidence of asbestoses, carcinoma, mesothelioma ar.d other tumours. It is also proposed to widen the field of enquiry to embrace ancillary occupations, such as transport, docks, building etc., which ray involve Xcss vCtieivc r*yiT50ciJtr,r' -to r'C*4'Jz~. .0.2, cn.n,"7' cC ~~*?^2~ should bo rigorously screened to determine, .-.uy pcssiol . -- .* exposure to asbestos dust. Pathological -- it was felt necessary to standardise criteria for diagnosis under the caroful supervision of a consultative panel of pathologists. An endeavour will bo made to grade the degree of pulmonary fibrosis duo to tho presence of asbestos and routine examination of sputum, fresh lur.g or fixed tissues (where available) for asbestos bodies or fibres will be incorporated into ail pathological cxe-vinatione. Physical and. chemical -- the possibility was discussed of establish ing a centre to produce a sot of analytical standards end to investigate the biological, physical and chemical characteristics of various types of asbestos fibre. Methods of identification, of the different types of fibre ir. largo samples of tissue ar.d in lung sections were also discussed. Investigations at the Pneumoconiosis Pesearch Unit, Llandough Hospital, South Vales, were designed to resolve.the suggested association between exposure to crocidolite dust and diffuse pleural mesothelioma occurring without intervening asbestosis, and betveen asbestosis and. subsequent lung carcinoma (V'agner, Bull. Bn. int. Cancr. 1965, (2), UCC 020760 2). The following mechanism could provide a possible explanation: Heavy exposure ----------Vtsx0s aobcSt03is to dSOOStOS - Bight exposure (especially to croeidolite) Ho fibrosis, but -> aoteoios bodies or fibres in -> Pulmonary carcinoma 1 Diffuse mosothelior -> of ploura or peritoneum This pattern would go far to explain previous reports of low incidence of mesothelioma, especially where pathologists only considered the existence of this particular tumour in those cases showing frank asbestoses. The study of Nouhouso St Thompson (loc.cit.) revealed that in 47 casco from the group showing positive mcootholioma, wharo tissue from biopsy or necropsy or sputum could be obtained for examination, JO (62.y/t) showed ' evidence of either asbestos bodies or asbestosis; but ..to majority of thooo showing frank asbestosis were 'workers actively enjagcd ir. handling the raw catorial and therefore exposed to high concentrations of dust over long periods. It was also shown that the heavier and longer the exposure, the shorter was tha interval before the onset of symptoms and tho time of death. Obviously, therefore, the danger of incipient mesothelioma is present among those who are exposed through contact with a relative or who live in the vicinity of a factory and are thus subjected to only minimal exposure. Suspicion has been focussed on croeidolite as the causative agent in mesothelioma, but in most British factories a mixture of croeidolite, amosite and chrysotile is liable to be present in the atmosphere and mesothelioma may perhaps be caused by all or any of the various constituents of the dust. Studies on the organic components of asbestos are being carried out by Karington et a.. (Top. 3r. Smp. Cancer Campn 1964, Ho.42, p.2j). Two fractions of oig--tic material can be' determined: oils present naturally and oils arising from contamination during the manufacture or transport of asbestos. Extracted samples of a particular batch of amosite which had previously appeared to be noncareinogenic, or only weakly so (Wagner, Nature, Load. 1962, 1 r6, 130)7 have been found to be associated vrth the development of mesothelioma ir. hamsters (Salikoff, personal communication in 196.4 to Kurin, ;tcn o c a I. '(loc.cit.). A. r.ample of the organic extract us now being given inirnperitonoaLly to rats as part of n long-ter;:, test. Other work -in progress includes investigation of the possible tumour-initiating activity of croeidolite and amosite oil in conjunction with tha promoting agent croton oil (3I3RA Bull. 1962, 1_ (2), 37). 7. has boon shown that during a storage period of 6 months asbestos ,,osorbs 7O-05?j of the jute oil present in jute sacks (Karington, Trans. N.'f. Acad. Sci. 195; In press). One sample of extracted jute oil was shown to have tumour-promoting activity when a known carcinogenic polycyclic hydrocarbon was used as initiator. Wagner (loc.cit.) also reports on the relevance of the presence in asbestos of aromatic polycyclic hydrocarbons, including 3,4-bencopyrene. No hydrocarbons have been isolated from chrysotile (the most widely used type of asbestos), but croeidolite, which was mined in that area of South Africa with a high incidence of mesothelioma (Wagner et al 3r. J. ind. Med. i960, 1J_t 260), contained 3,4-benzopyrene in relatively high amounts. The suggestion has also been made that asbestos carcinogenicity may bo related to the metals or metal complexes contained in asbestos fibres; chrysotile contains nickel (O.53I) and chromium (O.17S), while amosite has manganese (0.75) Serum can elute a trail amounts of nickol, chromium, manganese and magnesium from chrysotile, and iron and manganese from UCC 020761 A 07062 , V . * * '\ 51? - crocidolite end arosite (Sarington et al. loc.cit.). Pleural mesotheliomas, similar to those found in human cases, can he established by intrapsritoneal injection of asbestos into hansters (Smith & Ulsasscr, Join Proc. Peon An, Saaa exp. Biol. 1965, 24, 550)* Thera io a sroat sense of uxGancy in tho coarch for a nolution. to the complex problem of the netiology of menothelloma. Cellular otudiao r.r loir,:: undertaker. ray contribute to an ur.de ra tending of the 'underlying nerkrairn. filled ar.i asbestos are both fibrcgcr.ic, 'jiving rice to aiiisocir and acbostoaia respectively, but ciiica is r.cr.-careincgcnic except when introduced into specific sites such so tho pleural cavity of experimental animals. The effect of silica and asbestos on lysosoces and phagosomes (phagocytic vacuoles) in macrophages is being studied by Harington U Allison (Hep. Br. Hap. Cancer Canpn 1964, Pa.42, 0.24). When iitrn up by the phagocytes, inert materials have negligible effect on the , wh*.silica (anti presumably asbestos) causes tM ii.i ! 1 V f' ;i a to ilie yl f ,. t-o I ,r. I 'jet octU I lie ' 1' ' 1' 1 ``.tJl ( U I I Si A ! '.t, I I , 1 * m ,. ( I ( 1. ) , ) Auluiysid follows ana, ultin* tody, coil death ami fibroiiis. ITltiii (to lion can be neutralised by polyvinylpyridine-N-oxide which is taken up by phagosomes and lysosones and apparently binds directly with the silica surface, preventing its toxic effect. Asbestos studies on similar lines are now in progress. However, awareness of the problem and willingnesn to tackle it cannot completely mack the sobering thought implicit in this quotation from the report of the Vorking Group (loc. eit.): "........... further cacos of those associated tumour: are expected tc csever for many years to cone, even if dust exposures are now greatly reduced". Bust exposures are in fact increasing, for the problem is not only confined to workers in the asbestos and contiguous industries. It concerns all of us who have ' asbestos boards in our ceilings and walls, asbestos cats on our ironing- boards or asbestos installations around the water pipes. Ultimately, some form of control over the manufacture, distribution and use of" asbestos products is to be expected, but until such time, the prognosis of mesothelioma indicates the need for restraint end care in the handling and use of this potentially dangerous substance. UCC 020762 A07063'