Document B7LdzY3mVag2Zv7DEBxKYeZ8

*4 *4 * . >V l: 2 ij;i LA MEDICINA DEL LAVORO VOLUME 61 - 1970 INDICE fC6nC& THIS MATERIAL may be protected by COPY RIGHT IAW iTlTLE 17 U.S. COik. MILANO DIKFXIONF E AMMINISTRAZIONF VIA 5, BARNABA. H 174 Mat. L, oro lstituto di Patologia Generate dell'Universita di Perugia Dircttorc: Prof. A. Cvputo PATHOLOGY OF VINYL CHLORIDE P. L. VIOLA During the last years a syndrome characterized by alterations of the ske leton, teguments, nervous system and hepatic function *3-4-.has been observed among the workmen associated with vinyl chloride polymerisation process. An experimental programme has been performed in order to eva luate the toxic effect of vinyl chloride on the animal organism, and in order to try to reproduce in rats the acroosteolytic lesions observed in man. Materials and Methods Twenty-five Wistar male albino rats, of average weight 150 gr., were exposed to vapours of vinyl chloride 4 hours a day for 5 days a week during 12 months. The animals were kept in a plastic air-tight container through which there was a constant flow of air containing 3 % in weight, equal to 30.000 p.p.m., of vinyl chloride. At the end of treatment the surviving animals were killed at twenty-day intervals, and the paws, brain, liver.'kidneys and thyroid were examined histolo gically after .fixation, inclusion and colouration by the ematoxylin-eosine. Van Gieson, PAS, Weighert, Bielschowsky-Gomori methods. Twenty five rats of the same breed were set aside as a control. Results During the period of exposure the animals were slightly soporific, but the first few months of treatment were well tolerated and the rats showed no change in body growth or behaviour and no organic alteration visible macroscopically or by radiological means. After ten months some of the animals began to show a decrease in weight, in agressiveness. in their reaction to external stimuli, and often a disturbed equilibrium. Thirteen animals died from cardio-respiratory complications. Two animals died from hematoperitoneum. Most of the animals showed pathological involvement of the brain, liver, kidneys and thyroid. Six rats showed histopathological alterations of the skeleton. The small metatarsal bones showed an extensive periostal proliferation of cartilage-like material apparently originating by metaplasia directly from the bone. All around the newly formed cartilage the cellular components were compressed and arranged tangentially to the cartilage itself, forming a peri chondral layer. The isogenous cartilagenous groups were irregularly arranged and their nuclei were of varying size and often number per cell. The edges of the cartilage were irregular, showing digital extroflexions resulting from a varying growth potential. There was also evidence of chondroid metaplasia in areas of mature compact bone, in which the cartilagineous elements were t l,,I *>/ I F.y i chloride s 1 V/t'(/ Z_i/t ,,t Pc; lieu )E erations of the skehas been ride polymerisation :d in order to evanism, and in order rved in man. were exposed k^Bng 12 months. gJ^Which there was 000 p.p.m., of vinyl killed at twenty-day e examined histolotoxylin-eosine. Van nty five rats of the soporific, but the e rats showed no cation visible mame of the animals their reaction to een animals died from hematoperinent of the brain, cal alterations of istal proliferation isia directly from components were . forming a periigularly arranged r cell. The edges is resulting from draid nmetaplasia ^>n<ents were [ ,,/ 61 II 3.!lOl> 01 ll\*l ( III OR[Df 175 Fit- l * Pertoxial proliferation of metatarsal bone of a rat, lfilh months old. exposed to vinyl chloride sapours fur II months (.hematoxylin and'eosin). Fiy I - Periost.1 pfniitvrjtMtn .! met.oarsjl Nnv >t a rat, U>lh months ld. exposed u* Vtml hlnride vapours !,r mi'itilis ihen\at**x\ Im and c<>xin 176 VIOl A W*. La torn I .>/. t/ L i1 s> 1 -h|F'5' 3 ' Peri"'Ial proliferation of metatarsal bunt of i rat. 16th months old. exposed lo v.nvl .hlor.de vapour, for i; month, (hematoxylin and eoiinj. inyl Fiy 5 vm>l chkir 1 i f- * . in> I u`-i, Lava yot. A/, . J, 1970 pathology of vinyl uiioridh 177 iQnths old,-exposed io vinyl " Fi#. 5 * Chondroid metaplasia in mature bone pf metatarsus of a-rat. 16th months old. exposed to vm>l chloride vapours for 12 months (hematoxylin and eosin). Fvi tt - t metapl.i'.u m mature N*nv **t mvui.O'.U' t a rat. ttnh month'* old csp.*^^ '.mis* t-hli'rvk \.ipour* it>r 12 rin*nxlt> (hcina^'s Hit jiiJ cv'ini 178 V /<'c/ Lu i <*r> grouped around a central nucleus of bone, as in typical osteochondromatosic processes. In the small bones the chondroid metaplasia was often very exten sile and the bones seemed to be impregnated with a mucoid substance which altered the characteristic disposition of the bone tissue obliterating the ce ment lines. The skin of the paws showed areas of hyperkeratosis superficial thickening of the epidermis, vacuolization and degeneration of the basal layer, disappearance of the cutaneous adnexa and modest accentuation of the papiilar layer of the derma. An almost constant state of edema was observed in the epidermic zone. The connective tissue showed dissociation of the col lagen bundles and a diminution and fragmentation of the elastic reticulum. The small arterial vessels showed signs of endothelial fibrosis with a thicke ning and dissociation of the elastic membrane, often accompanied by a partial hyaline degeneration and homogenization of the walls and proliferation of the endothelium. Some of the vessels appeared completely blocked by a pro liferation of the connective tissue in a formation not unlike that of onion skin. The small nerve bundles were often surrounded and invaded by fibrotic processes. A microscopic examination of the brain revealed diffuse degene rative lesions of the grey and white matter. The external granular layer was often reduced and in some areas this was true also of the medium sized and giant cells. Numerous examples werefound of hypercoloured, atrophic neu rons with disappearance of the nucleoli and sometimes also of the nucleus itself. At the level of the white matter there were zones of intense, reactive gliosis consisting for the most part of cytoplasmic and fibrillar astrocytes, some of which were arranged in a concentric disposition around the blood vessels. There was evidence rif neuronal phagokarvosis with satellitosis and the deposition of neuroglial elements around the altered nerve cells. There was modest proliferation of microglial elements, especially in areas of "more intense gliosis and zones of intense spongiosis showing an accumulation of astrocyte-type elements w'ith basophilic cytoplasm and abounding in gemistocytic and microglial elements similar in appearance to scavenger cells. The cerebellum showed signs of atrophy of the granular laser which was often represented only by a few isolated nuclei. The layer of Purktnje cells was in some places profoundly modified, the cells appearing us be under going intense degeneration and all the various stages of this process were observed, from the whole cell to the small homogeneous bodies with indi stinct outlines which represent the most damaged form of the cell. Except for small and limited areas, the molecular layer seemed to be well preserved. The liver was often of increased volume, sometimes subicteric in colour, with a smooth surface and somewhat more brittle consistency than normal. A histological examination showed in the majority of cases signs of diffused interstitial hepatitis with numerous hepatic cells in the grip of regressive pro cesses varying from torbid degeneration of the cytoplasm to necrosis with marked cytoplasmic and nuclear polymorphism. Some of the hepatocytes showed giant or double nuclei. In these areas of cellular necrosis a corpuscolar exudation was always present consisting of round cellular elements of the lymphocyte or plasmacellular type. There was evidence of an abnormal proliferation of the Kupffer's cells, which were often hypertrophic. The trian gular spaces appeared to be increased by the infiltration of round and polynucleated cells and eosinophilex showing marked poly morphism. The portal capillaries, centrolobular veins and sinusoids were often blocked bv numerous l ,1/ ;/ centrally steatosis necrosis of viral cases ev degeneu The treatmer sometim The rafollicu The leton or This of vinyl milar to in a ma pointed cartilagi commar of Toky ring pla limit va bv auto The chlond 1 p hoiK'-x Ml mcupldM nuP'hct x \ No rutidn vtr infiltrated in the h V101 \ P I riM.i di Pintle a quelle una inte II eonne volmenit. Jyfnu p- dini* \.r v *v*i te S4eU. Lavoro chondromatosic ften very exteniubstance which terating the ce- tosis superficial the basal layer, tion of the pa- i was observed tion of the col- lstic reticulum, with a thickeed by a partial >roliferation ef eked by a pro of onion skin, led by fibrotic iiffuse degeneular layer was iumsized and j^vhic neu- nucleus tense, reactive lar astrocytes, md the blood atellitosis and - cells. There ireas of more umulation of ig in gemistoenger cells. r which was 3urkinje cells to be under process were is with indicell. Except II preserved, ic in colour, han normal, s of diffused ;ressive proecrosis with hepatoeytes 'is a corpuar elements n abnormal . The trianIjMlpoly- Wp1ortal v nammeerous Vol. 61. n. 3. 1970 PATHOl.OtiY 0^ VINYJ CHt.OKIDI 179 centrally-located areas of partial necrosis, often accompanied by a diffuse steatosis in the form of small drops with clearly-defined areas of acidophile necrosis and the formation of elements similar to the round acidophile bodies of viral hepatitis and the * Cauncilman bodies of yellow fever. In certain cases evidence was found of an intense fibrosclerotic reaction alongside the degenerative processes. The kidneys did not appear to be eccessively altered by the prolonged treatment with vinyl chloride, although they showed signs of tubulonephrosis. sometimes accompanied by chronic interstitial nephritis. The thyroid often showed a colloid goitre and a marked increase in pa rafollicular cells. The control animals showed no histopathological alterations of the ske leton or of the various organs. Conclusions This research confirmed that the animals are sensitive to the toxic action of vinyl chloride. The lesions of the bone and the connective tissue are si milar to those noticed in experimental osteo-latyrism and to those described in a man affected with acroosteolysis of the hands (Marin). It should be pointed out that the roentgenological findings of skeleton in man rests on cartilaginous transformation of the bone tissue. Therefore according to recommandation made at XVI International Congress on Occupational Health of Tokyo (1969)7 I should like some precautions to taken in the manufactu ring plants polymerizing vinyl chloride, such as reduction of the threshold limit value of monomer, and substitution of manual cleaning of autoclaves by automatic devices. SUMMARY , The results of this investigation show th.it animals exposed to vapours of vinvl chlorid mux show degeneration of the skeleton und connective tissue with hisloputhological pictures similar to those observed in human acroostcolvsis of the hands. The bones in fact undergo processes of intense pcriostium growth and dilfuse. chondroid metaplasia. The connective tissue is dissociated into collagen bundles with a reduced number of cells, the elastic leticulum is markedly reduced and fragmentary, the small vessels of the deep layers of the derma show hyperthrophy of the walls with a dimi nution and sometimes obliteration of the lumen, the nerve endings are surrounded and infiltrated by fibrous tissue. Dcgenciutivc processes of the parenchyma were observed in the brain, in the liver and in the kidneys. R1ASSUNTO Viol \ P. L. PatnU>vw Jti ( Itiniro ill I inile. I risultati di questa indagme dimostruno che gli animuii esnosti ai vapori di eloruro di vinile presentuno munifesta7iom generative dello scheletro e del connetuvo simili a quelle osservate negli uomini atfetti da ucroosieotisi dellc mum. Le ossa presentuno una intensa prolifera/tone del penostio ed una dilfusu metaplasia eondroide multifocale. 11 connettivo e dissociaio in fasei eollagent poveri di cellule, il reticolo elastico. notevolmentc diminuito. e ndotto a del (rammenti, i piecoli vusi degli strati prot'ondi del derma presentuno ipertrotia dclle pared con diminu/ionc e talvolta oblitera/ionc del lume vusaie. le tormina/ioni nervose sono inglobate e dissociate da tessuto libroso. Manifesta/ioni degenerative del purenchmiu sono slate visservate nel ecrvello. ncl legato ISO v 101 \ Wt'i/ Li/ioro iV VIOL \ P. L. ZUSAMMENFASSUNC. Lrkrttnkiinven durelx Vinyh lilnrni. C Die Ergebmsse der vorliegenden Umersuchungen /eigen, dass hei den Versuchstieren nach Ematnuina der Dampfe von Vinylchlond Veranderungen am Skeleti und am Bindegewebe auftreten. welche denen von Menschen ahneln. die an Akroosteolyse der Hande leiden. Die knochen zeigen eine starke Proliferation am Penost und elne diffuse fleckfdrmige Metaplasie der Knochenstruktur. Das Bindegewebe ist in zellarme kollagene Strange aufgelbst. die elastischen fasern sind bis auf Fragmente vermindert Die kleinen Gefasse im Umerhautbindegewebe zeigen eine Verdickung der Wixnde mit Verengung odor gelegentlich voiliger Verlegung des Gefasslumens. die Nervenendigungen sind von fibrbsem Gewebe umgeben und durchsetzt. Degenerative Veranderungen des Parenchyms warden im Gehirn. in der Leber und in den Nieren beobachtet. IL Come in REFERENCES I) Cordier J. M . FiEvtz C.. Lefevre M. J.. Sevrin A. f 1966): Cahiers de Medecin du Travail. .4. I. 2) Chatelain A.. Motillon P. (1967); Journ. de Radiol et d Electrol.. 5. 277. .1) Marin A- StRsus.s I.. Miuufls R.. Benoit J. A.. Bai.tie R Pierre C. (1967): Rev. du Rhumat.. 6. 340 -- 4) Harris D. K. Adams W G F (l%7): Brit. Med. J,, J. 712. 5) Wilson R. H.. Me Cormk k W. F Tatum c' f' Creech J. L. (1967): J.A.M.A.. 201. 577. - 6) Suciu L. Drums* I.. Valssksi' m` (1967): Med. Lavoro. 58. 261, -- 7) Viols P. L. (1969). Proc. Int. Cong OecuDat' Health, Tokyo, ' costituisce ui piu grave, f formazione t of Noise r lire i prowe un rapporto visto nei sut cita sull uot tenuto per combattere cost delta Act 1936, e del 1960. T numerose c legge sped! Noise fin iegge: inoli multe previ cese polem tl966) e H i! National una malatt pensation A. ehe la sor ambient! l in realta. i denominat consideraz si realtzza 11 rum danneggia non orga Aeisee in i),, i l i, vt_r i