Document Ra4OgOyO9VYrmnL103p6XDLMv

- ** 0 Medicinn del Lavoro March 1970 (Vol. 61, n.3.1970) pp 174-179 Translated from the Italian Istituto di Patologia General dell'Universita di Perugia . Direttore: Prof. A. Caputo PATHOLOGY OF VINYL CHLORIDE P. L. Viola * During the last years a syndrome characterized by Iterations of the skeleton, teguments, nervous system and hepatic function^-* 2, 3, 4, 5, 6 ^as been obseived among the workmen associated with vinyl chloride polderisation process. An experimental programme has been-performed in order to evaluate the toxic effect, of vinyl chloride on the animal ciganism, and in order to try to reproduce . in rats the acroosccolytic lesions observed in man. MATEri^LS 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. Ac the end of treatment the surviving animals were killed at twenty-day intervals, and the paws, brain,- liver, kidneys and thyroid were examined histologically 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 macrosdopically or by radiological means. After ten months some of the animals began to show a decrease in weight, in agressivcncss, in their, reaction to external stimuli, and often a disturbed equilibrium. Thirteen animals died from cardio-respiratory complications. Two animals died from hematopcritoncum. Most of the animals showed pathological involvement R&S156978 ( -2- Pathology of Vinvl Chloride P. 1j. Viola of the brain, liver,`kidneys, and thyroid. Six ratrf showed histopathological alterations of the skeleton. The small metatarsal bones showed an extensive periostal proliferation of cartilage-like material apparently originating bv 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 perichondral layer. The isogenous cartilagenous groups were irreg- . ularly arranged and their nuclei were of varying size and often number per cell. The. edges of the cartilage were irregular, .. -- .showing digital extrofloxicr.s 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 grouped arourd a central nucleus of bone, as in typical osteochondromatosis processes. In the small bones the chondroid metaplasia was often very extensive and the bones seemed to be impregnated with a mucoid substance which altered the characteristic disposition of the bone tissue obliterating ihe cement lines. The skin of the paws showed areas of hyperkera.v"' tosis superficial thickening of the epidermis, vacuoliai tion and degeneration of the basal layer, disappearance of the cutaneous adnexa and modest accentuation of the papillar layer of the derma. -An almost constant state of jedema was observed in the epidermic zone. The connective tissue showed dissociation of the collagen ----------bundles and a diminution and fragmentation of the elastic retic ulum. The small arterial vessels showed signs of endothelial JEibrosis with a thickening and dissociation of the elastic membrane, often accompanied by a partial hyaline degeneration and homogeniza tion of the walls and proliferation of the endothelium. Some of the vessels appeared completely blocked by a proliferation 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 degenerative lesions of the grey and white matter. The external granular layer was often reduced and in some areas this was true also the medium sized and giant cells. Numerous examples were found of nypcrcolourcd, atrophic neurons with disappearance of the nucleoli and sometimes also of the nucleus itself. At the level of the white matter there were zones of Jitcnse, reactive gliosis consisting for the mostr part of cytoV-- plasmic and fibrillar astrocytes, some of which were arranged in a concentric disposition around the blood vessels. There was cvidcnco of neuronal phagokaryoais with satellitosis and the deposition of neuroglial elements around the altered nerve cells. R&S 156979 s 4 -3Patholoov of Vinvl Chloride P. L. Viola 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 with basophilic cytoplasm and abounding in gemistocytic and microglial elements . similar in appearance to "scavenger" cells. The cerebellum showed signs of atrophy of the granular layer which was often represented only by a few isolated nuclei. The layer of Purkinje cells was in seme places profoundly modified, the cells appearing to be undergoing intense degeneration and all the various stages of .--this process were observed, from the whole cell to the small homogeneous bodies with indistinct outlines w>-\ch 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 processes varying from torbid degeneration of the cytoplasm to necrosis with marked A-- cytoplasmic and nuclear polymorphism. Some of the hjpatocytes 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 triangular spaces appeared . to be increased by the infiltration of round and polynucleated cells and eosinophiles showing marked polymorphism. The portal capillaries, centrolobular veins and sinusoids were often blocked by numerous 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 excessively altered by the prolonged treatment with vinyl chloride, although they showed signs of tubuloncphrosis, sometimes accompanied by chronic interstitial nephritis. * The thyroid often showed a colloid goitre and a marked increase in parafollicular cells. R&S156980 < -4Patholonv of Vir.vl Chloride P. L. Viola . The control animals showed no histopathological alterations of the skeleton or of the various organs. CONCLUSIONS ^his research confirms that the animals are sensitive to the toxi action of vinyl chloride. The lesions of the bone and connective --tissue are similar 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 roentgen"ological findings of skeleton in man rests on cartilaginous transformation of the bone tissue. Therefore according to reccomendation made at XVI International Congress on occupational Health of Tokyo (1969) I should like some precautions to . be taken in the manufacturing-plants polymerizing vinyl chloride, such as reduction of- the threshold limit value of mon cier, and . substitutionof manual cleaning of autoclaves by automatic devic* es. SUMMARY The results of this investigation show that animals exposed to vapours of vinyl chloride may show degeneration of the skeleton and connective tissue with- histopathological pictures similar to those observed in human acroosteolysis of the hands. The bones in fact undergo processes of intense periostium growth and diffuse, chondroid metaplasis. The connective tissue is dissociated into collagen bundles with a reduced number of cells, the elastic reticulum is markedly reduced and fragmentary, the small vessels of the deep layers of the derma show hypertrophy of the walls with a diminution and sometimes obliteration of the lumen, _the nerve endings are surrounded and infiltrated by fibrous tissue. Degenerative processes of the parenchyma were observed in the brain, in the liver and in the kidneys. NOTE: Figures on available copy were not suitable for reproduction. They are as follows: . * Fig. 1 -- Periostal proliferation of metatarsal bone of a rat 16th months old, exposed to vinyl chloride vapours for 12 months Fig. 2 -- Periostal proliferation Df metatarsal bone of a Tat, 16th months old, exposed to vinyl chloride vapours for for 12 months