Document RpeM7BGXDRYz5J3BEvkmEB1wE

.. .7'*: 4*.-- 7 /). c.' dry.t .y/ /Cf .vy,,-w ^ >V j . X- . - 514 / $- /-< 7 -vat the silicone fluid is devoid of silica granules. [?ha intense fibrous tissuo reaction and tha nrc;...-.cj of doubly rafraotile crystals in tho lesions described by Winer c ; cl. ( ' ,.;- ) ds-'o not been rop-orted by other workers using p'iro liquid <.r ;;o.' 1 ; qilieo.-ica. Two .if the tiiroo siliccnu preparation:., referred to i.y lijnor ; : -.1. ('tnc.r.i j.) contu.r.O'l .jiixai rad vegetable fatty acics, boll: of v.-.ich art* cur.u.,:e of inducing in their owr. right tho severe jranulorsitous reaction oLccz-vgu. It is quite probable that a significant or over, tisjor role was played by the fatty acids in the induction of the reported severe fibrous lesicr.s. If we are to believe the claim of the existence of silica grmuics in tho siiicor.o fluid preparation, then it is conceivable that the silica my have beer, a contributory- factor in tho production of tho tissue reaction. However, a very reliable source of ours had no hesitation in refuting the claia that silicone fluid is contaminated with silica. Only under conditions of extremely high temperatures and high pressures ar.d in tho presence of oxygen is oxidation of silicono fluid to silica possible. For this reaction to proceed during shelf storage is not only highly inprobaolo but wall-niga impossible.] PLAINTIFF'S EXHIBIT MESOTHELIOMA A Ml ASBESTOS The development of tumours (mesothelioma) following exposure to asbestos dust tends to be insidious (3I3KA 3ull. 195< 4, i1!)- The initial obstacle to recognition of the harard lay in correlating two episodes -- axpos-ore to asbestos dust, however light, and subsequent development of the tumour. Once this connexion lad been established the problem assucod new ar.d somewhat alarning dimensions since the time-lag between cause and effect my well extend to over half a century. Before 1530 the industrial and commercial ir.portar.ee of asbestos in this country was still relatively oral!. Thus it is only now that the incidence of diffusa pleural or peritoneal mesothelioma can be expected to show a steady upward trend- This pattern is bococir.g all toe apparent. Public interest in tho problem should certainly have been alerted by a report in the r.unday Tiros (ji October 1915) on the work cf hcvhousc 1. Thompson (Hr. .1. ink. Med. 1063, id, 2(i1), Their iapomuLt epi.l.-r.io- logical study covereif *15 patients talcs and 42 fciiilos) with positively diagnosed diffuse pleural or peritoneal r.esothaliesa nUnittod to the London Hospital over the course of approximately 'jO yr. IVieor.ce of exposure to asbostos was obtained in 4O of the J6 cases whose background historioo could bo traced with relative accuracy. Of the remaining >6, 11 nad lived within half a r.ile of an asbestos factory'. In a control group of 76 in-patients, notched for-sex and ago, only 14 gave histories of previous direct or domiciliary exposure to'asbestos. The rise in reported cases of asbestos bodies in the lungs my reflect either an absolute increase in incidence or the results of more searching pathological examinations in the light of this r.ew knowledge. 2o that as it say. Catena et al. (j. An. med. Ass. 195j 1 92, 571) report a 41$ incidence of asbestos bodies seen in tho course of 110 routine adult autopsies (475 in unics; in fannies), although r.sno were founu before tr.o ago of 24. Ho cases of nosotholioaa or asbootosis could bo identified and primary ccncor of tho lung was only prooont in lr./o patients - ono with asboatou bodies ;md ono without. Tho authoro draw attention to UCC 020759 A0706C' . - 515 - the problem of positive identification of the asbestos body and the differentiation between it end the similar structure encounterod in talcosis. They believe that the problem is rate acre difficult because of the similarity betveen asbestosi3 arising from exposure to trenolite and talcosis. Mistochsascal differentiation is thought to be necessary, but the method used in the present study was ciectrcn-probe analysis. .Vcncihclcec, the authors rejected fiodines which did net positively identify classical asbestos bodies and still produced an incidence rush hi,"h"r Ulut previoun studies had revealed at autopsy, notably 2ri. 47* in Cape Town (Thomson ct -.1 S. Afr. r.cd. J. 19(53, V7, 77) and s7 9/5 in Pirn: (Themeor., Conference on Biological Effects of Asbestos, few 'fork, October 1964). Trench workers have also drawn attention to the problem, or.d an analysis of histcpathelogicai findings has been published (Turiaf et al. Prcs.cc nod. "'9(55, 22> 2199). Although the asbestos industry in that country is not large,- the incidence of mesothelioma is rising ana concern is understandable. Hecordirg the incidence of asbestosis and mesothelioma and standardising diagnostic techniques formed part of the terms of reference of the '.vorki ; Group convened, under the auspices of the Geographical Pathology Comities of the International Union against Cancer (I.tT.C.C.), to look into the whole nuesiion of asboatoa and cancer. The comprehensive report of the Group (ur. J. ind. Ked. 19^5, 22, 165) recommends three main linos of attack: Epidemiological -- more information is required concerning the results of exposure to particular types of asbestos fibre (ancsite, crocidolite, anthophyllito, chrysotila or tror.olito) by inter- and ir.tronational 3tudi3 in specified areas. It is recommended that studies be 'undertaken into the relation between dust dosage, the physical state of the dust and the incidence cf asbeotosis, carcinoma, mesothelioma and 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 less intensive c;rsecure to e.sb''ster. .Ml eo.str r rv kh''.w should be rigorously screened to determine. -.y ecu: i . ; exposure to asbestos dust. Pathological -- it was felt necessary to standardise criteria for diagnosis under the careful supervision of a consultative panel of pathologists. An endeavour will lie ratio to grade the degree of pulmonary fibrosis due to the presence of asbestos c.nd routine onanimtion of sputum, fresh lur.g or fined tissues (where avc.ilrble) far nsbcr.tce he-ies or fibres will be incorporated into all pathological c.xmir.ations. Physical at A chemical -- the possibility was discussei of establish ing a ccr.ur- to predv.ee a set of analytical Standards ar.d to investigate the biological, physical and chemical characteristics of various types of asbestos fibre. Methods of identification of the different typos of fibre in largo samples of tissuo and in lung sections were also discussed. Investigaticno at the Pneumoconiosis Research Unit, llandcugh Hospital, South Ve.los, were designed to resolve, the suggested association between exposure to crocidolite dust and diffuse pleural mesothelioma occurring without intervening a3bcstosis, end between asbestosis and subsequent lung carcinoma (i.'ogner. Bull. TJn. int. Car.cr. 1955, 2 (2), UCC 020760 516 - 2). The fallowing mechanism could provide a possible explanation: Heavy exposuro to asbestos Light exposure (especially to crocidolite) -> 'Prank asbcctosi3 l/o Cibrooio, but -> asbestos oooiao ---------> or fibres ir. tha lung of pleura or poriicneua "-.is pattern would go far to explain previous reports of lev incidence of rosetheliema, especially "here pathologists only considered tha existence of this particular tumour in those eases showing frank asbestoses. Che study of L'owhouso St Thompson (loc .cat.) revealed that in 47 cases iron tho group showing positive mesothelioma, whero tissue Iron biopsy or necropsy or spurns; could be obtained for exanination, JO (62.5$) showed ' evidence of either asbestos bodies or asbestosis; but ...c majority of those showing frank asbestosis were workers actively engaped ir. handling the raw catorial and therefore- exposed to high concentrations of cast over long poriodo. It was also shown that the heavier and longer the exposure, tha shorter was tha intorval before tho onset of symptoms and tho tine of death. Obviously, therefore, tho danger of incipient nasotholioma i3 present among those who aro exposed through contact with a rol.itivc or who livo in tho vicinity of a factory and aro thus subjected to only minimal exposure. Suspicion has been focussed on crocidolite as the causative agent in mesothelioma, but in cost British factories a nixture of erocidolita, anosite and chrysotiie is liable to oa present in the atmosphere and mesothelioma nay perhaps be caused by all or any of the various constituents of the dust. Studies on the organic components of asbestos are being carried out by Harington et al. (l-p. 3r. Bap. Cancer Conpr. 19c4, i'o.42, p.2j). Two fractions of material car. be determined: oils present naturally and oils arising iron contamination during the manufacture or transport of asbestos. Extracted samples of a particular batch of asiosito which had previously appeared ts be r.cncarcinogenic, or only weakly so (Vagner, Wat'ire, Lor.d. JcZ, * r6, t c,0) ~ have been found to be associated with the development of neocene-iom hamsters (Solikol'f, personal communication in 1964 to iiirington on_ . (1 Qc cl t. ). A cnnplo of tho organic extract is now it-,.r.,p ,;.vrr, pcritoruviily to rats as pari of a long-ter;:, test. Other wok: n: pro press includes investigation of the possible tumour-ini tlating activity of crocidolito and anosito oil in conjunction with tho promoting agent croton oil (BIDRA Bull. 1962, 2. (2), 37). 7. has boon shown that during a storage period of 6 months asbestos .orbs 70-05$ of the jute oil present in jute sacks (Karington, Trans. H.'S. Acad. Sci. '965; 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. Vagner (loc-cit.) also reports cn the relevance of the presence in asbestos of aromatic polycyclic hydrocarbons, including 3,4-bensopyrer.e. jfo hydrocarbons havo beer, isolated frGa chrysotiie (the cost widely used type of asbestos), but crocidolite, which was mined in that area of South Africa with a high incidence of mesothelioma (Vagner et al 3r. J. me. n6d. IJoO, 1_, 260), contained 3,4-benzopyrene in relatively high amounts. The suggestion has also been made that asbestos carcinogonicity nay bo related to tho metals or metal complexes contained in asbestos fibres; chrysotiie contains nickol (0-5$) and chromium (0.1$), while amocito has manganese (0.7$). Scrum can elute Email amounts of nickol, chromium, manganese and cagnosiun from chrysotiie, and iron and manganese from .t UCC 020761 407062