Document 0bmvMxpR8Boqozzd9kDk26gm

*? **& &;_ ,v<'M;Jfe.-.. ST0095341 AKPCtCt Of OEMKtt lKTBW defect found was not related to the appearance of bronchitic symptom*. Prospective, todies are needed, however, to confirm the situation regarding these lung-function studif Immunological action of TDI The major problem in any study of the effects of human exposure to TDT is the separa tion of its irritant from its potentially Sensitizing properties! Some indication of an immuno logical response has been obtained in animals {O'ed ut FC.T. 1965, V&45} bat attempts to demonstrate such a response in apparently scnjiii/ed workers have Onled, although com plexes of TDi with human scrum albumin stimulated the lymphoqfits in time sensitized individuals (ibid 1970, 8, 2.15). Further attempts to demonstrate Circulating antibodies in human scrum have been made in 55 worker* all with symptomsSuggesting TDI sensitivity (Taylor, Pnc. R. Soc. Med. 1970, 43, 379). lh this study, ucoipplcment fixation method, a red cell linked antiglobulin technique and a ^uxhtied passive cutaneous anaphylaxis test in monkey skin were used. Although 23 of the patients reacted positively in at lea*: one test, correlation of results between the tests was podr, indteayfig that they detected antibodies either of slightly different specificity or of different.tnubuaogiobuliaclare. Until suitable laboratory diagnostic tests for TDI sensitization kin devised, fhti Wtid?njjiiliil rrtiilmnihiji between circulating antibody and symptoms of clinku asnsltusUMaegJp|^adli^ilf4--ibtMC4*re. Immunological studies in monkeys and guinea-pigs failed to shoW whether Ibe effects of TDI on respiration in man are likely to involve Palmer, ibid 1970. 43, 380). Although exposure of the to TDlrioderettit more susceptible to subsequent exposure to tow leofft efUtt immunological techniques prevented the ^Tawing of thelnaiteiguaeyofcurrent u j whether thi greater sensitivity "" Cot.Jtukm More information is to TDi and pos&ibiy the TLV, reduced hi Future lung-functioo bnd monitoring TDi kfitim 1970,43,368)awofirtMf>. Introduction ASBESTOS: QUESTIONS STILL UNANSWERED ^ Occupational exposure toresbestos 8uy ki<d to the formation of asbestos bodies in the lungs and to the development of ikbcstosis and tumours (mcsotlwliaiiittydf^rplccra and peritoneum (Cited in F.C.T. 1970,8,207). ThcaetM>logieal relatiewhips Mtwecn asbestos oodics, asbestosis and lung tumours are poorly understood and the presence of isbestos bodies in the lungs of the general population complicates the issue stiU further. Morccever, epidemiologic*! studies are still in their infamy and the importance of the nature, severity and length of asbestos exposure in tumour development needs t be more dearly defined. Improvements in the working environment introduces relatively recently should reduce the occupational health hazard sign.ficantly, alihnujh the full benefits to be gained may be masked for a time by the experience of past exposure. tJC.T. til--" 212 ARTICLES OP OENERAL INTEREST Fxperimental and epidemiological studies Allhough epidemiological studies have attached special significance to crocidolite in the induction of mesothelioma! tumours, other forms (amositc and chrysotile) have produced tumours m expcnmeiu.il animals, and chrysotile has been claimed to produce tumours m man (//>/(/ (>, 657; ibid I*>70, X, 20X). All three forms produced mesotheliomas when administered mtr.ipleurally to SI'F or Standard rats in the form of a suspension containing 20 mg dirt (Wagner & Hcrry, Hr. J. Cancer 1969, 23, 567). The percentage incidence of mesotheliomas was 64 for chrysotile, 59"' for crocidolite, 59"' for crocidolite from which oils had been removed by extraction and 40",' from amosite in SPF rats and 69, 6X. 64 and 31 in the corresponding groups of Standard rats. In general tumour incidence was inversely related to survival times, but the group differences were more marked in SPF than in Standard rats. IX-aths from mesothelioma occurred earliest in the chrysotile group (353 days m Standard ratst. followed by the groups treated with extracted crocidolite (376 days), crocidolite (417 days) and amositc (557 days) but after this time lag there was a rapid onset of mesotheliomas. It was necessary to distinguish between mortality from mesotheliomas and from natural causes and this was achieved using life tabic methods, but a mathematical model has been tested and found suitable for analysis of experiments involving smaller groups of animals (Ifcrry & Wagner, ibid 1969, 23, 582). The study described above was initiated in I^Z and work is now in progress on several additional projects, including an attempt to establish a dose-response relationship in rats by injecting crocidolite and chryso- tilc in a range of doses anJ a study using the inhalation route, which is more relevant to human experience. Fpidcntiological studies are gradually helping to ascertain which forms of asbestos arc carcinogenic. In Australia, IS cases of pleural mesothelioma have been reported in workers exposed to asbestos for 6 months-30yr (Milne, Med. J. Aust. 1969, 2, 669). Some workers had a history of exposure to crocidolite. In an informative review, Wright {Am. Rev. resp. Pis. 1969, 100,467) cites unpublished data presented at a symposium on pneu moconiosis held in South Africa in 1969. Reference is made to the inability of anthophyllite and chrysotile to produce mesotheliomas in Finnish and Canadian workers respectively. The Finnish workers exhibited odteMsis afid i three- to fivefohl increase in the incidence of bronchial cancer, but CnnO^M,^|prkefShowcy HO evidence of an increase in bronchial cancer. Mesotheliomas workersui some but not all of the crocidolite mines in South Africa so faM^|ttN|MMihtrihutgeM!eptions being the crocidolite mines in the Transvaal. Less surpismS^M|||,!feteas*Ociatcd p the chrysotile mines in this area, hut a few mesot hetK>yS^wH8Sl>i4 ths TnHHvaal amoskc mines have been recorded. Vigliam et al. (Medna Lar. kfpuki find no evidence of increased cancer of the lungs or pleura in Italian workers' exposed to chrysotile. Wright (toe. at.) also refers to a report indicating that chrysotile penetrates to the deep lung structures less readily and is cleared from the lung faster than either amosite or crocidolite. Summing up these epidemiological findings, it would appear that crocidolite and. to a much lesser degree. amosite produce mesotheliomas, while anthophyllite and chrysotile do not. In considering some of the apparently anomalous findings, Wright (loc.cil.) suggests that asbestos acts as a cocarcinogen rather than a true carcinogen, but the justification for reaching this conclusion on ilie supporting evidence must he questioned. The possible existence of a dose response relationship between severity of exposure and hronchiat cancer is also discussed and seents a more tenable proposition. j j ] j i j | j j i ) j i i , i ST0095342 AH I l( II S 1)1 I.ISIIIM INI I HI SI 2X? I ' i . <`i die i.iiih'' i*1 tle.ith among 45()u workers in an asbestos factory during I'*1' i'"-i New house i/>. / iml \h;l. IW<. 26, 2'/4) found (hat (lie mortality rale started loevsieii i i ,e 11. i :: i ,.;ur ioyr lioin ihe lust exposure to mixtures of amosiic. croodoliic i"'h:,i so;.,e \ s,;'ii,i,s .mi esse-s oi We.itiis inun eatieer of ihe lun^* and pleura even among wo; kei s with (ew 11), oi a 2-\ r period o| sen. we and from respiratory disease m workers wit it inoie piolongeii serv iee no eonlmed to the heuv dy-cxposcd groups. A retrospective exami nation oi death ecitillsates, autopsy reports and histological specimens pertaining to 301 woieis troin an asbestos factory revealed an underestimate of mesotheliomas in the ecituicd sauses of death. 15 tiddilional eases being discovered in 84 histological rc-cxuminulions, but :ne incidence of bronchial cancer had not been greatly underestimated (Ncwhousc & Wagner. ,//./ I'mv, 26, 302). Moderate to severe asbestosis was found <n all confirmed cases oi lung carcinoma. .-Is/'t Onv-/oi/1 ftini.ulinii I ne mechanism of formation and the aetiological sigmlieance of asbestos bodies have been discussed earlier {( tied in iX'.l'. l'J7li. 8. 2<W). More light has oeen thrown on the deseiopment of an asbestos body from an asbestos fibre by elec.ronm.croseopie studies invoicing either intratracheal instillation of soft or harsh chrysotdc or amosiic into hamsters (Sii/u k i ck. (Imre. him ir. /fw. 1%`f 3. 107) or intrapleural injection of chrysotdc into guineapigs (i).i\is. I.\pl. mol ruth. i'f70, 12, 133). These and earlier studies {Cited in h.C.T. 1`hiS. 6. 65*M suggest that the process entails the coating of the asbestos libre with acid mneopoKsaccharide before its phagocytosis by the alveolar macrophages, and Che subse quent transfer into the phagosome of haemosiderin granules which have accumulated in me surrounding cytoplasm. The libre thus becomes coated with a layer, or sometimes several layers, of dense granules to form an immature and subsequently a mature asbestos boiiv. I he bodies, which are produced largely in giant cells, are first seen about 2 wk after asbestos administration and their numbers increase to a maximum at about 6 wit. Asbestos bodies are forme J from fibres longer than 5^ and the process may involve no more than 0 1 of all the fibres present. Davis (/or. cit.) also provides evidence suggesting that in guinea-pigs the surface ol the acicJ mucopolysaccharide coat serves as a depository for the laying down of calcium (in the form of apatite crystals) in the development of the fibrous lesions, w lneh. eventually calcify to produce plaques similar to those seen in human asbestosis. The sigmlieance of ashestos bodies in the development of asbestosis and malignancy remains to be defined. Dickc & Naylor (/)/>. Client l%4, 56, 122) identified asbestos bodies in scrapings of the lungs and lymph nodes Irom I*) out of 100 autopsies of members of the general population in Michigan, although the presence of asbestos fibres in the bodies was not continued. In only four of these cases were asbestos bodies found in the sections of lung tissue. Morphological evidence of asbestos bodies in the lungs of asbestos workc's with mesothelioma was obtained at each of nine autopsies but asbestos bodies were not found m mug tissue removed from similar workers at thoracotomy (Milne, loc. at.). In seven of me mne autopsy cases, the ashestos bodies were found in routinely stamed sections of lung tissue. Otto & von Iragstem (Arch. Gaecrbcputh. GewrMiyg. 1 %9. 25, l')3) observed sp.>rud.e needle-shaped particles in normal and silicotic lungs and an abundance of these particles in the lungs of men with a history of asbestos exposure. Histological similarities between asbestos bodies and these needles became evident when the needles exceeded 20 n >n length. Differences in the prevalence of these needle-shaped particles in the lungs are claimed to be of diagnostic sigmlieance. 284 ARTICLES OP GENERAL INTEREST Asbestos haemolysis Chrysotilc (but not crocidolite, amosite or anthophyllitc) haemotyses human erythrocytes in vitro {Cited in F.C.T. 1970, 8, 210). In a study of the mechanism of this phenomenon, Schmt/cr & Pundsack (F.nvir. Res. 1970, 3, I) inhibited chrysotile-induccd haemolysis of sheep erythrocytes in vitro with cthylcncdiumine' ttraacetic acid, carboxymcthylccllulose and certain polystyrene sulphonate polymers, but polyvinylpyridinc-/V-oxide proved less clle.tive. Hus pattern of inhibition is the opposite of that obtained with silica-induced haemolysis. Clirysotile is considered to owe its haemolytic activity to the surface area or dcjtrcc of opening of the fibres. The exposed surface of chrysotilc is essentially magnesium liydr ixide, while the surface of the other forms is more like that of silica, further work showed that chrysotilc heated to 1000'C still retained haemolytic activity although the pattern of its inhibition was more like that of silica haemolysis than of haemolysis by un healed chrysotilc. The significance of this hacmolysic action to the in lit o situation in man is, like several other aspects of the asbestos problem, still questionable. A COLUMN OF MLRCURY: PART II In our last issue we considered v irious ways in which man and domestic animals may be exposed to inorganic or organic mercury (Hg). It now remains foMis to look further into the fate of this element within the animal organism and to try tar relate this to its known effects. / Brain levels of //? / While contamination of food has been shown to be a formidable hazard under certain conditions {Cited in F.C.T. 1971,9, 140) inhalation is projwbly still the route which offers the greatest likelihood of intoxication. The preferential uptake of Hg by the brain following parenteral administration especially via the lungs is well known {ibid 1967, 5, 101), but further demonstrations of this effect have recently been reported. Cassano et at. {J. S'europath. exp. Neurol. 1969, 28, 308) have studied the distribution of Hg in the brain tissues of mice and rats exposed to :o3Hg-labclled vapour at/a concentration of about 8 mg/m* for 6 hr daily for 10 days. Whole-body autoradiography of mice was carried out at the end of the experiment and at intervals up to 60 days afterwards. Micro-autoradiography of mouse and rat tissues was carried out immediately, ;ihd at intervals up to 50 days after the last exposure, brain extracts being measured for J,,Ilg activity for up to 120 days. The highest Hg concentrations were found in kidney, bratn and myocardium. In brain tissues, the highest concentrations were seen in certain neurons of the cerebellum (particularly in the nucleus dentatus neurons and Purkinje cells) and in the spinal cord, medulla, pons and midbrain. The general indication was that after penetrating to the brain, inhaled Hg was preferentially retained in nerve cells in two forms, probably as free I Ig and bound to proteins. These two fractions appeared tv) be in equilibrium, since the decay of radioactivity in them showed parallel courses with time, Nordberg & Seremus (Acta pharnutc. tox. 1969, 27, 269) have reported that the Hg concentration in the brains of guinea-pigs exposed for 5 hr to radioactive Hg vapour at a concentration of 7 mg/m3 w;cs 3 9 times higher than that resulting from 0-4 mg llg kg given intravenously as labelled mercuric nitrate, a finding in close agreement with the results ul an earlier study in mice (Cited in F.C.T. 1967, 5, 101) and of another by the same