Document yryDqg4x85b6zrqGzKRY97G24

TRANSLATION Med interna 15:967-78, (1963) INVESTIGATION OF THE DISEASES PRODUCED BY VINYL CHLORIDE Dr. I. Suciu, I. Drejman and M. Valaskai (Translated into French) From the Division of Industrial Hygiene and Occupational Diseases and the Department of Industrial Hygiene of the Institute of Hygiene of Cluj. The rapid development of the polyvinyl chloride industry in our country has raised for us a problem in industrial hygiene, toxicology and occupational pathology. In the aim of investigating this problem, a group of hygienists and clinicians have examined the conditions of work and the diseases affecting the workers of two plants manufacturing polyvinyl chloride. The clinical manifestations encountered raise the, problem of interpretation of the ctiopathogenesis, of theoretical as well as practical importance, and of defining the clinical picture as well as of the necessary preventive and therapeutic measures. Our study was necessary in view of the fact that the existing scientific facts at our disposal were few and lacking in detail, especially as regards the observed clinical manifestations. Danishovskii (1) had demonstrated that the monomers, the starting products, exert an aggressive action from the -biologic point of view. They have the property of producing destruction of the skin and of the mucosa. Some of them are allergens. They act on the parenchymatous organs by producing degenerative changes and on the hematopoietic system, leading to an anemia of hemolytic type. Hervieux and Tessier (11) found, among 145 workers of a polyvinyl plastics factory, 17 cases of chemical dermatitis.** Pletsitzer, Bondar and Smirnova (cited by Danishevskii), in studying the chronic effects of the vapors of vinyl chloride, observed in man the development of toxic angionaurosis. Dr. Lefevre given the reference as Medicina interna 6, No. S:963-77, 1962} in Index Medicus (6:N-1277, 1964) the above reference is given. The original is being ordered. ** In fact, in their account, the authors speak of 17 cases of "intolerance" or only 10 cases of pruritus, without eruption, of the forearms and of the face appearing in the summer, as seeming to be due possibly to vinyl chloride. SPI -12764 Vl-.oiio few clinical studios have not permitted, ftt tho present tifr.o# tho elm rnc turir.a lion of a clinical p icture. Concerning experimental'work, Mnsiromattoo, Fischer, Christie and DniiBiger (V) In studying tho toxic action of vinyl chloride, on a croup * 5 rats, 5 mice and 5 guinea pigs, demonstrated tho appcaranco of contention, of tho livoi* ann lungs after. nijiwaiud exposure to mu'ootio done# of 10, 20 to 0p7i. In the animals that were sacrificed or that died during expocuro, a congestion of tl>o liver and Sidney, and in homo eases, oven a fatty degeneration of tho livur woro ibsorvod. Among tho toxic eubctnncoo, Lnzaroov includes vinyl chlorldo among tho mild narcotico. In pursuing tho study of tho clinical symptomatology of workers exposod to tho monomer vinyl chloride, and by moans of laboratory tests, wo concludod that our findings permit tho definition of a clinical picture which.may aid tho practicing physician in tho recognition of tho first symptoms of acuta or chronic Intoxication by vinyl chlorido and of rocommending mcasuros for prevention and treatment. Laboratory studios havo added somo data concerning tho mechanism of tho pathogonosls of thosa intoxications. Thoso clrcumstancos havo convinced us to publish our findings. Material and Method of Investigation In tho course of 4 years, we have had under observation 1G8 workers ongaged In tho manufacture of polyvinyl chlorido (PVC) in two factories: 54 workors in plant "A" and 114 in plant "b". For tho most part, tho subjects wero young, below 30 years of ago and havo novor worked in any other Industry. Pre-employment medical and detailed laboratory examinations were carried out in order to provont tho hiring of thoso who would prosont some contrain-' dications. Records wero maintained in tho porsonnel filo for each caployoo of the results obtained in tho course of routine medical examinations and on tho occasion of tho thorough examination, clinical as woll as laboratory, dono annually. In addition to tho'medical examination, tho following laboratory analysed woro dono: Bysprotoincmia test Electrophoresis of sorun proteins DSP hepatic "clearance" Cold prouaor toots Digital plotfryemography In certain casos. SPI -12765 Yho can or. that exhibited clinical nervous, digostivo, cutaneous and angioneurotic manifestations, woi'y routinely hospitalized in the clinic Tor occupai local disease:; in order "to carry out tho complox laboratory testa and. to establish therefrom, IX possiblo, tho causo o tho lntoxi" cation. Thereafter, it was necessary to examino tho clinical manifestations and tho results of tho tosts In order to characterize tho clinical picture and to Xormulnto preventive mensuruu. RCfttilts and Discussion Wo have observed that at first contact with tho poison, no:>t frequently at the time oX changing tho charges, during emptying or leakages due to various causes, particularly the nervous manifestations appeared. AXter 3 months to 1 year of employment, digestive disturbances were added to tho nervous disorders. In certain eases, the nervous manifestations changed into angioneurotic manifestations (Ilnynaud syndrome); finally, in o.thcr cases thcro was scleroderma or chemical dermatitis. At times, oil theso . disturbances appeared at the samo time (see clinical observations). In order to characterise this clinical picture nora clearly, wo a?o presenting tho objective symptomatology observed in its increasing ordor of disturbances, so that tho physician may recognize this intoxication from its Xirst symptoms. We are describing them with the frequency found for tho various clinical manifestations so that their significance may bo appreciated. In tho order of nppoarnneo of the symptomatology produced by vinyl chlorido, we shall arrange them into tho following groups of manifestationsi nervous, digestive, angioneurotic, and cutaneous. liorvous Disorders Certain workers stated that at the Xirst exposure to the monomer, or vinyl chloride, the first inspirations have an agreeable taste which thoy could not define exactly. This is compatible with the opinion of Sebit (cited by Dortishevskii) who stated that tho monomer, or vinyl chlorido, has a pleasant ethereal taste, and with tho opinion of Lazareev (4) who holds that this substance cannot bo tasted except at narcotic doses of 7 to 10%. After several inspirations, a euphoric stato sets in; 11% of the subjects xng, whistlo or laugh. (Tho euphoric stato and the pleasant taste persist for only a short time). Most often, during exposure to tho P*sontho subjects experience a heavy feeling .in tho legs, are no longer ablo to coordinate movements and become dizzy (47%). According to them, this stato Is similar to alcohol intoxication. These disturbances.occurred most frequently in tho courso of tho manufacture ing process, at tho end of the charge, during the dischargo of latox, as at other times when the monomer io released in concentrations as high as, according to Petre (9) , mg./u^'./'nich io greatly in ox-"so of tho maximum permissible limit of 0.03 mg/m'*,* -V * Translator*s notos (applicable to jiomania). In tho USA, tho TL is ,,iI.->i?.00:.-.g/n^*, or 500 ppm. SPI -12766 Subsequently, in ;TiT* of tin* cam:;, uor.u'iolcnco sots' in, wnieh <*minic alertness and can occasion wurit accmcniii. After a stay An tho open a in, tho symptoms diminish progroasivoly, then disappear. In the enso oT G woi'kcrs who wore engaged in tho repair of certain Uofectivo parts, complete narooalo ppeax*ed, which dloapponrcd after thoy were removed into the open air. After a porlorf of oovoi'nl tncmiiui oi working in vhio onvironMonz, a eta to of somnolouco poruistu aftux* working hours. At homo, tho oubjoctu exhibit a hypersomnia, sleeping between 0 and 14 hours a tiny. Ono pcroon slept, with a brief lntorval, continually for two days. Tho sloop is deep, without dreams. From this point of vlow, particular attention must bo paid to,night work, because tho workors could easily fall asloep at tho work slto. When thoro is an abundance of vinyl chlorido vapors, thoi*o arc complaints of formication of tho lower oxtremitios followed by a sensation of heat over tho entire body. s, Sinco the monomer vinyl chlorido is lighter than air, it could bo that it acts directly on tho integument; this would agreo with tho opinion of Danizewski (1). Anorexia, .attributed to tho toxin in 23% of tho casos, sots in rapidly. In 12% of tho casos loss in weight of 4 to 17 kg. occurred, Aftor repeated exposure, headaches aro reported (36% of tho cases), norvousness (9%)t faulty memory (3%), insomnia (3%) and a general asthenia (7%). Theso symptoms indicate tho establishment of a neurologic asthenia subsequent to moro prolonged exposure to tho ppison. Wo wish to point out that in most of tho casce, wo hrivo `observed theso clinical symptoms without considering tho significancot of tho rosiotanco of tho organism. *' In general, aftor the first symptoms, protective aoasurcs for tho . werkora wero instituted ao as to prevent tho appearance oi acuto intoxication. According to existing knowlcdgo, it seems that tho poison haa a momentary narcotic action,oven after ropoatod exposure. .In cortain cases, a .neurologic aathonia sot3 in. Digestive Manifestations Aftor a variable poriod of time, in tho course of whicji, tho nourologic canifcHtnilono predominate, digoutivo symptoms appear. SPI -12767 Tho first symptom which-presents itself Is anorexia (li37. of tho C.'.ooo). This indicates n general intoxication. Subsequently, Vertigo appoare (in 16% of the eases) and, more rarely, celesta. Later, pains in tho epigastric region follow (107. of the cartes), a feeling of discomfort, of heaviness, of pressure in tho right hypochondrium (7% of tho.cases) or of the left hypooiiondrium (bf, of tho eases). Tho patients present pains, of tho boring typo, which however do not osfiutic tho naturo of pancreatic attacks. All express p d is too to for .fats/ Upon objective examination, in S0..2% of tho eases, a hopatonegaly without ictorus has been established. The liver exceeds by the costal border 2 to 3-fingcr widths without a lowering of tho upper lir.lt of tho liver. Upon repented examinations we have found that tho border of the liver has an clastic consistency, then becomes harder and acqulrco tho consistency of epidemic hepatitis. Wo have found that 67. of tho hepatomegalies bccamo lator complicated by splenomegaly. After removal from exposure, without other treatment, tho hepatomegaly regressod and in the majority of tho casos, tho ovorali condition bccamo normal. . Our observations show that in many casos hopatomegaly dovolops without any association, with tho digestive symptoms. We have observed tho fact that in 6.87. of tho eases who had formerly experienced epidemic hepatitis, the hepatomegaly had appeared moro rapidly, although at tho timo of their employment in tho factory, tho livor was within normal limits. Tho enlargement of tho liver pointed out to us tho difficulty of an otiopathogcnic interpretation. Tho question arose of tho diagnosis of toxic hepatomegaly or of that duo to anicteric virus infection. This is why most of the patients afflicted with hepatomogaly wore hospitalized in tho department of occupational disoaeos. Granted that: tho hepatomegaly appears after repeated exposuro to tho poison; tho bordor of tho livor is of soft and uneven consistency; tho hepatomogaly disappeared after change in work without othor treatment; it appeared in a group of pcoplo who wero subjected to treatmont by injection among whom there woro casos of epidemic hepatitis; in spite of tho absence of thcco manifestations in tho othor sections of tho industry, it had not been supposed, nt first, that tho onlargcmont was of toxic naturo. Tho hypothcoie of an occupational origin is fnvorod also by tho fact that in patiento oubjoctod' to chronic intoxication by load or mercury, before the SPI -12768 establishment of attacks of develop is;; illnci; a (lead colics) wo cor. ohmorva A similar hepatomegaly which 'disappears afterk vi'OiiUuOflt with (^0) Laboratory tests carried out by us woro: electrophoresis .of sorum protoins. thymol ronction zinc 6ulfnto toot bremsulphaloin (DSP) toot, and liver biopsy. Electrophoresis of scrum proteins (ooo Tablo X in Appondix) shows among tho 36 eases with hepatomegaly; a diminution of albumin, bolow 537.: 11 timos; an incroaso of moro than 5% of C^-globullns: 10 times 0% of or^-globulins: 20 times 13% of 0-globulins: 9 times 21% of Y'-elobullnst 10 times. This shows that tho oloctrophorotic pattern is identical with that of viral hepatitis - in which principally tho Gt2-globulin is increased. Wo noted that tho thymol reaction, the "zinc sulfate, and the Greenstedt testswero positive only in 6 eases which shows us that in the determination of disturbances, tho olcctrophorcsis of scrum proteins is of particular valuo. Two cases of 11 showed a pathologic'chango in response to tho BSP test, indicating that tho livor.jlcsions arc not localized in tho parenchyma. tho Since we have found hepatomegaly without protein changes and with a normal BSP, ono night bo led to bclievo that the poison producos a transient congestion of tho liver, identical with that demonstrated experimentally; this in turn shows that tho hepatomegalies which wo havo observed are of toxic naturo. As a result of repeated intoxication, tho congestion can chango Into a toxic ncuto hepatitis, accompanied by olcctrophorotic changes similar to1 thoso of viral hepatitis, and finally, thoso lesions can bccomo chronic. In 2 eases in which hepatomegaly persisted for moro than a year and in which tho border of tho liver wau of firm consistency, a llvor biopsy revealed tho plcturo of chronic hopatltis. SPI -12769 .y.C- .V 4 i :?0 -patients i tli hepa tin;; the son'll aidolano v.i," found `.0 inovngeii between 0.mg, ;> ami i . i\0 i* in I / c>t(tcu ;.ui*Ci **n iiu Slrbu) l(-)j which demountraton tha L Lite a! Joint#o lovcl it; tho sensitive lout. A fact to be'kept in wind in that we have also found a codification of the protom metabolism among workers exposed to tho toxin who wore not afflicted with hepatomegaly (sco Toblo II). Of tho 2G casoa oxaminod, wo found: on OlbuBiin lovol lowor than 507.: Id timon, on lncrooso of ooro than 07 of Ct -globulins: 6 times i 9% of cro-globulinu: 16 times 137# of ;3-globulina: 8 times '25% of y^lobulins: 0 times. This shows us that disturbnnccs of tho protein metabolism can prcccdo hepatomegaly in certain eases, anti that the poison sufficiently influences." this motabolisir.. Therefore, tho hepatomegalies that we have found aro principally of toxic naturo. At first, they are in effect congestive, and lator they assumo tho forms of acuto hepatitiG, identical with anictoric viral hepatitic; cortnin onos of them can bccomo of chronic nature. h'o'wish to ernphasizn tho fact that the disturbances of the protoin aelaboiicra can appear in certain eases before tho onset of hepatomegaly. Our investigations show that olcctrophorcsis of scrum proteins and determination of aldolaso activity are of greatest importance in tho bio chemical diagnosis. At tho last examination, in 97# of the eases, a dyspeptic.syndrome of ulcerating type was demonstrated, although wo were unablo to discovor any radiologic changes to this effect. In the knowledge of the predominantly narcotic action'of tho poison, it is more probable that tho derangement of tho cortical dynamics after repeated exposuro leads to a disturbance of tho diencephalic contcrs which comes into ploy in tho pathology of theso manifestations. Y/o continue our observations. Angioneurotic Manifestations These veto domonatrablo in 67, of tho cases in tho form of tho Sayr.aucl syndrome. (TUstribution ao to sox: D/'Y of the canes wore men.) Vi'o rjl,ght mention tho fact that in 3.67. of tho casoc with Itaynr.ud'e eynuror.o, there was also sclorodorma and hopatomogaly SPI -12770 i V*> i 11 us v.iv.to i i. c clinical pic luro i.-.oro cloariy, wo v.sn to oj.to tho lullO'./vi'.|; observation: Case- 1; VV., ;.iale, ngcu ?.<> yours, .has been cn;;.`.;;co foi* It years ;r. tho i'i'ocos;; of polyi.e rl /.avion. I'nwily mid personal history, normal. Smokos .0 ^ to i'.O cigarettes dnijy. At the beginning,- the patient, observed that during the release of toxic vapors, there was first a euphoric state and then n elate similar to inebria tion. At homo, ho slept between !> and Id hours daily. At work*, his hands ii.-.morr.cd in tno latex, bo iolt formication, numbness, and then n'sensation of boat. When tho solution was white, he observed a coloration of the skin. In contact with cold water, it was obsorvcci that tho fingers became pale, then red and cyanotic. Concomitantly, the same phenomenon appeared on tho great toes. This occurred also upon exposuro to cold* air. At tho same timo, ho was affected by persistent edema of cyolids, of tho face, tho neck and chest; tho skin became glossy, the nails "unovon" and.the faco assumed tho appearance of a full moon. From tho clinical point of view, a Raynaud's syndrome was oviclcncod, hepa tomegaly with sclcrodormin of the face, neck and thorax, even of tho lowor and upper extremities, but particularly of tho fingers (dormatologic examination nado by Dr. Capusan). Musculocutaneous biopsy showed typical changes of doruatomyoaitlG (Dr. V. V. Pa'pilian) . Tho plothysmogram showed significant inhibition of tho vasomotor contorG. In addition, tho urinary 17-ketostoroids woro increased to 8.5 mg. in 2d hours. Tho lunar facies nado us think of ft thyroid insufficiency. Tho iodine uptake confirmed this belief. The dysprotoincmia tests, electrophoresis of scrum proteins and tho BS? test gavo normal results. By its narcotic action, tho poison produces firs" cortical inhibition;then appear tho disturbances of tho diencephalic centers, principally tho vasomotor and metabolic disorders. Tho symmetrical naturo of tho vascular disturbances, tho plothysuographic changes and even tho tissular disturbances and tho cclorodcrma vouch in favor of this fact. The thyroid insufficiency, evidenced by the iodine uptake, shows that tho poison has oithcr a direct influcnco on tho thyroid or an indirect ono via tho "hypothalamus-hypophysis," which prociucoa Inhibition of thyroid function. ^ After removal from exposuro, the scleroderma and tho vasomotor disturb groatly diminished. 03 / SPI -12771 In half of the cr.so.s, pi i: liiy.'.inogr y showed r.h inhibition o;` too vasomotor center:;. A;; to foe ri uir..J* *'. It S | tU <* '(!* It V * \VIi u * P *; v;w;.*u norm.-.!. Jisjitfc i.\i iy in the tfftsc.'! whore liio p i,t! iT.i.i ViWi i w r.nr.1, the dir,iurbaneos d1^appeared cor.plo 1 oi y .liter removal *ro:n the toxic exposure, but 10 the rest of the coses , they greatly diminished , which would indicate their 'connection with 1 ho toxic environment. By hc.M'.s of tho cold pressor tent and by tension oscillography, Ban ckc.' ,, Suciu nnd Disiaru have found paradoxic;.* reactions and an absence of reactivity in GG% of the canos in plant "a" and in G.V.i of the eases in plant B, vhien pointed out to uj that vinyl chlor*<io uotorjiinoo tho vasomotor disturbances in a c>`cm number oi tho cases. Only 01* oi the e&iios had clinioul man**'oi*tations (Baynaud'o syndror.io) . As concerns tho changes in arterial tension, wo found that the maxima os woll as tho minima wore icoro than 10 to 1G mm below normal valuos. Cutaneous Manifestations Pruritus, which was found in 4.8% of tho eases, without boing accompanied by skin changes, was tho earliest symptom. Later, two different categories of cutaneous manifestations could appear. Tho first noted was contact dermatitis, then sclorodorma could bo oosorved. 1. Contact Dermatitis (4.Aft). On tho face and hands (uncovered parts), pruritus followed by urticaria wore noted. Papules, microvcsiclos and largo vosiclos appeared on tho face and hands. There were eases v/aoro tho mlcrovesicics and tho scabs disappeared spontaneously, but in othors they wero torpid and, aftor `roturn to work, they reappeared with intensity. Case 2; K.I., chemical technician, 28 years old. According to his personal history, ho had suffered epidemic hepatitis in 1942. Since then, he has had frequent anginal attacks. He has been working for a yoar and 0 months in the division whero sodium mcrsolato is mixed with different substances. In December I960, micropapuics in plaquc~form appoarcci or. tho forearms and face,, then microvosicics, scabs of which remained. Tiioso eruptions wero pruriginous. Upon hospitalization in tho department of occupational diseases, zonos of microvcsiclos and areas of scabs woro noted on tho face and forearms, as well as largo vcsiclos at othor Giton, which after opening, left tho skin covorcd with largo scabs. The vcsiclos contained a serohemorrhagic 6ccrotion. Sedimentation rate, 2.4 nm/hour. .':3 Leucocytes G,000 per r.m of which 75% woro polynucioar, 10% lymphocytes, G'i monocytes, G% eosinophil a. Bed cello: 4, GOO, GCO per r.mP ilemogl'Gbin lovol: 92%. othyemography revealed an inertia of ho Vasomotor centers. SPI -12772  no es ioils disappenred after t reu i j1t .v, Ui an ointment of c.ol';" COrt lni'.c niu! wivomye i n . They immed i tely upon nts /oUM to vorlij even upon touching coi'ta in oiilji:ci;; n i/, his hond:,. This i.V.ovt. that not only the inorsoln to but vinyl chloride as well wo Poaponr.iblo.* Change ir. work brought complete ci isnppearanco of tho dorr, a tit is . 2. Scleroderma (3.G% of tho canon) In the course of work, certain worker:; note a pleasant odor, followed at tii.ioi; by omottonal and iso tor di i.turbnncou, d i .`.xiaos;; and svi'-uoloncu will eh, in tlo c.-.sc of some, persists after tho end of tho working clay. Others report ion.ucnt .on and numbness of tho extremities. Case 3: T.8., ago 20 yoars,. has worked for a year and 6 months-at tho autoclaves, iic has worked at no other sito. i'air.ily and personal history rovealed nothing remarkable. Alter a year and a half of exposure, diffuse pains developed in tho lower and upper extremities, with edema. They were interpreted to bo rheumatic pains and treatment brought r.o relief, An nmygdalcctomy was performed. After return to work, a generalized pruritus developed on tho faco, neck, chest,tho abdomen and the extremities. Dermatologic examination (Dr. Capusar.) revealed edema of tho eyelids, faco, with disappearance of ridges. Tho skin ovor the abdomen and tho chost could no longer fold. I .On tho face and chest, grayish spots woro soon, that aorgod togothor nG in tho ease of chloasma in pregnancy. This clinical picturo was interpreted as scloroderma. Tho liver was enlarged by 2 fingor-widths. Tho Takata-Ara reaction was faintly positivo. Tho thymol tOGt yioldod 14 units. Tho protoinogrnm showed: total protolns: 8.6 g% albumin: 48.70% C: -globulina: 4.85% .Cf -globulins: 10.50% p-globulins: Y'-globulins: 14.70% 21.20% Consequently, clinical and laboratory examinations demonstrated tho presence of toxic hepatitis. lAO U Z X O 1* tctwcniont np,>onrr; to bo &auiuJ.'icio;tly. cupportou.. (r.*;l`co v* T. O * \i SPI -12773 Vi*e A ; i vOl* liOi'iV.;! b ro!.!!. vi! (2v*0 u Oi tit! v i v i'(. 7* , * "* v'^ Pi e thy :....og raphy ovu'.cnco'. u .:.a dcp i on of the . Oi* Oi:r vOI*# U ! l .* * <i ]',o v r.':! pond to stimulation. Vi.oru'u test uliOWv'i a;' ai > a i*or* ;o;\ and cor. cciiti'iuioii tests normal results. Vr.u t puCiaaC Gyeamxc activity of proteins was normal. Tho iodina n p t a k o tost indicated hypofuncUioning of tho thyroid. Arterial tension vac 1*1/7 cr.i Kg. Urine was norm.nl. In this case, ns n result of exposure to tho poison, disturbances of tho vasomotor centers and of tho protein m-.-t.aholism (changes in tho protoinograw in tho dysprotcincmin tent) developed. Thyroid insufficxcncy and chronic hepatitis woro found concomitantly. Knstromattco statos thnt in polyvinyl chlorido intoxication, a thyroid insufficiency exists. It in interesting to note that in this ease, in tho period of ono year from tho timo of removal from tho toxic environment, tho sclorodorma, tho Raynaud syndrome and hepatomegaly hove disappeared. ThiG proves that a toxic source was connected with thes phenomena. In tho eases of scleroderma, the majority of the subjects presented a thyroid insufficicncy and an inhibition of the vasomotor centers. In 3 cases a dcrmomuscular biopsy was performed, which rovcaiccl chronic dermatomyosj.r.i.s. In ono case only did the manifestations of scleroderma fail to regress after removal from tho working environment. In tho other eases, these symptoms disappcarcd,which substantiates for us tho idea that these changes are operative in a reversible period. The manifostations of the scleroderma, accompanied by disturbances of tho vasomotor centers appear as a result of exposure to vinyl chloride and disappear after cessation of work in this environment, proving that this is tho poison that in this case has produced" the vasomotor disturbances and the metabolic oi the hypothalamus. Tho participation ox"tho thyroid in their production reduces the problem of this thyroid insufficiency to 2 eventualities: direct action of the poiGon on tho gland, or consequence oi thyroid inhibition of central origin. Tho manifostations of collngcr.osis, verified histologically, which occur in-cases of intoxication by narcotic substances, reveal to us that in tho.pathogono of coilngonosis there occurs at first, in these eases, a disturbance of protein metabolism duo to tho activity' of tho central norvous cystern and followed by tho appearance of an ondocrino disorder (thyroid, insufficiency). The reversibility of tho disturbances indicates in our opinion that" there is a pooexoxxity ox recovery xx tii.o/vustioa ...axes pxaco xn too initial phase. SPI -12774 Oi c*>i * OS i * * Uoi* i r. .* L t j oA O* oy< i"; i. pi* OliiCi' .SUk);i WiU'iKc \Cv. j i S *<** * * j '-"i viC 1 a**o (ic^cribo<i in vno iHornlin'o. Vina woulci conar;.. ou** O ,/..u * v.*-- t ;on!> A:; r. result of investigations into the environmental con;',ivions performed by hygicnis to n;ui physicians, recommendations were formal atod for tho protection of tho workers and for 1 onkproof i r. g the equipment. 1 a spite of these moauurcs, some cuses of the disease h..vo occurred during the past year. Thanks' to trontr.iont Instituted according to the indications of repeated clinic.'., onam 1 r.nlions, and .vtiioviii * ro.. too oav.rua..o.'..^ wo /u succeeded in controillag the oldest casco, givon that they woro unde.*taken during a period of rovorsibla disorders. Tho recognition by certain physicians of the manifestations that wo have just described ha3 permitted the detection of intoxications from tho start, and tho institution of adequate lacnourco of provontion or.d treatment. COXCI.US XOXS 1. Vinyl chloride and tho vinyl monomers possess a narcotic action and produce, depending upon concentration, in addition to characteristic neurologic manifestations, a stato of euphoria (12%), followed by a state of inebriation similar to that of alcohol intoxication. In cortain cases narcos in car. appear. After leaving tho working environment, a ctato of cotmolonco <d5r) poraists, with hypersomnia'. Vinyl chloride acts on the akin and produces a sensation of formication and of heat. 2. After repeated exposure, a neurologic asthenia 6ots in in which aoanolcnco predominates. .3. After a variable period of time, dyspeptic disturbances nro added to.the neurologic manifestations; these are at first not characteristic; they arc tho form of epigastric pains (167.), swelling, discomfort, fooling of heaviness in the right hypochondrias. (7%) or the left (5%) with anorexia, particularly for fate. In 30.27. of tho esses, congestive hepatomegaly appears, which may mimic VexiC hepatitis without Jaundice; come casos may become chronic. In G% of tho cases, the hepatomegaly is accompanied by splenomegaly. The P rot o * nog r ..m r.nc. tne r..vloiii r*oa. o ..io so..-.*, live tests one. sac..' c..sagos ito taooe o. ..cute aepa.itis; .iaioo ... g.osul.r.s a ..ci of t.*o p" SPI -12775 9LIZ lm IdS r f imoTacaooyvwtt $9 uoxx;mpo.id oqa ut zxvd o po/o^d oacu. g.Tocouos Xuta om puo opipjoTvo xjCuta mq* /[oATfJ'joop sn u.v.ou.o tAoti 'jj.toa Jo oSucip pa co.tnsoo'j! 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S u T '.'vo rX(- J LLLZI- IdS *\'?6T f ox\r.c;.-o?oo '"/I'S'S o*:oypu,av..,oo f *A*0*d vixroupqqp "t .'our.u: op ^cxpxc'/cpuc'O o u*:??/;:uoo~oox\wxrx vo^or.xaocio-<^-0 i. st\T,s<r *6 *^2 *d ' `-tu '9C *xa 'X96X '* Xqnd. *3/}{ *qux rjjro *1X^2 K SI&SIHO '*K *V HSHOSId '*2 OSii^OHiSVJfl *8 d f *.xu '`12. MA '096T ''went) ssy *5?Ah *aponpup jouo/ HsoizNva ^ 'siisiKo (,rv H2H0SI2- * *2 OSiiVKOUiSVK 'A *T96T 'p^o^o '*K*S*S t?t ojcT?oTunmoy 'optrpqo ep^psnpup uxp pp^oqpounuj er oxxoq Xnppo- p oq.trp^:?,p ooxq.daq .soXT^^ttqxna ox*? aoads xaufl o nmiis * *i NvsauriK '*i vjkvk *9 *6 <* *z ** 'X96T '(T^soanong) euox3j a m< $ *J1$bV 'Tasoancmg `sopinpoo, *ps'y#T xoA 'T^snpux uj oatoou ooxuixqo oaucqsons S. *A A2dVZV'I '*( X96X..' X'Jq~o qdos * p nxo 'oo-jurtuo poTr^qs.Tiprr? fc x-uoxSo^ToquT tfqupwrojuoQ eX oacopunwoQ 'oopqscid- ^ox^X^T-'0^"111 Ex^shpux uj Tpounu cuoxSp op ouoxqoag s Hoevo *C *S * 0HSSZN020 9 *d 't av 'g6X 'ptur *3po 'X VACX'OHO'IOd '*S *A VAOiVTCd *2 92 *d '6 *j: 'X?6X ''Aoxoqos jojx! cpp-x* -b-po *x *:: aohoou ' *s *i ixstesxxvc *M*X 'Ao.ioia ' 'IVS ' 77>:5A3ii!!7iscc " A:!cv^vr:!;;.u f* i ;> -*.0^ 0 t SUCjLU -l * , PxS^/w^U V*y *a5*V-/rXii"^T? tJL < Cercctari chinico-riaioio^ico si iciGnico-sanitaro priviv.d idbricarea rr.aoolor plasticc acrilico si vinilicc, Corr.unicaro S(S4*t/ iulio, I962. H iijSSi^,R ot -.2*\V I2UX Ai'ch. Xal. prof.t T.20, nr. 1> p. 61, 1959. 12, ?R*J??3a?. Aspects toxicolo^iquos .do lfindustrio doc ni iiiros plastilus's. Arch.; Mai. prof. ?.20, nr 1, p. 44,-1959. SPI -12778