Document NNqnV3JwJVqqMpV4dB3YQp63E

4 v / <PJL- ^CHNfCAL^^1^ OF ttediclna intorna (Bucharest) 15:057-74 (Au;.), 1053* ^^^RMatiqn^cenVer *r * {. INVESTIGATION' 0? TJiS DISEASES PilODuCS BY YIN*/- CELKIIDE Dr. 1. Suciu, I. Drojman and ii. Valaskal (Translated into Trench by Dr. Defovro) Vro* tho Division o Imiuttru. liy.tiono and Occupational S.scaooc and the Dapartmont ot Industrial Jlygicno of tho Institute of yjtono of Clu, Tha rapid development of tho polyvinyl chloride industry in our country hA* raised for us a problem in Industrial hygteno, toxicology and occupational 4. pathology. In the ain of investigating this problem, a group of hygienists ar.d clinicians have examined the conditions of work and the diseases affecting the workor* of two plants manufacturing polyvinyl chlorido. The clinical manifestations encountered raise tho problem of interpre tation of .tho otiopathogcnosls, of theoretical as wall as practical importance, and of defining the clinical picture as woll as of the necessary preventive and therapoutlc measures. Our study was necessary in view of the fact that facts at our disposal were few and lacking in dotail, * * obsorved clinical manifestations. t the oxlstir.g scientific especially as regards tho Darvishovskli (1) had demonstrated that the monomers, the starting product*, | ' exort an aggressive action from the biologic point of view. They have the * I - property of`producing destruction of tho skin and of the mucosa. Some of - them are allergens. They act on the parar.chymatous organs by producing degenerative change# and on the hematopoiotic system, leading to an anemia of hemolytic type*. . _ * I` Korvloux and Tessier (11) found, among 1<5 workers of a polyvinyl plastics factory, 17 cases of ehemlcal dermatitis.** ?lotsitzor, Bondar * and Smirnova (cited by Daniahevskii), in studying the chronic effocts of tha vapors of vinyl chloride, observed In man the development of tpxlc anglor.ourosis. * Dr. Lafevre givei the reference as Mcdlclna interna 6, Xo, 8:953-77, 1052; in Index Mcdicua <5:X-1277, 1964) the above reforonco is givon. The original is being ordored. In fact, in tholr account, the authors speak of 17 cases of "ir.tolor.'.r.co" or only 10 esaea of pruritus, without .eruption, of the foroaras and of the fae. appoaring in the summer, as seeming to bo duo possibly to vinyl ehiorldo. !*. ,.v. vl  * ; . * - . Tl^oso few clinical studio* iuvu i>; permitted, ftt tho proscftt ti*o, the .: Characterisation of a c.inlcal ;>iauri;< Concerning experimental work, i'.nntror.at ico, rischar, Christie and Danxigor (f) in xtuoying tho toxic action of v.nyl cr.lorido or. a group of ^ rat*, S mice and 5 guinea pic*; demonstrated tho appoarancc of congestion cf tho ;Ivor ana lungs after rupvAiud exposure vo n-ivoi;o uoo of i, 20 to 3C*. In tho an lamia that were sacrificed or that died iliiri;.* expoburo, a congestion of tho liver and kidney, and in some case*, oven a fatty *o;noraUon oi tho llVur wore obwoi'wtl. Among the toxic aubstancoe, Utaroev induces vinyl chloride asor.tho mild narcotics. In pursuing tho study of tho clinical eyr-ptomarology oi workers 0x7.010c to tho monomof vinyl chloride, and by means of laboratory tests, we concluded that our findings pormit tho definition of a clinical picture which.uay n.d tho practieinc physician in the recognition oi t,;o first oy=?to=* of acute or chronic intoxication by vinyl chloride and of rccomsor.dmg eeasuros for provontion and tjaataont. Laboratory studios havo added soao data concerning tho mechanism of tho pathogonesla of those intoxications. Thoso-olrcuastanceo hove convinced us to publish our findings. - ?f Material or.d Method of Investigation %r ' In tho courso of 4 yosrs, wo havo had under observation 1G8 workers engaged In ths manufacture of polyvinyl chloride (?VC) ir. two factorios: - 54 vorkors in plant "A* and 114 in plant "b", * Tor tho most part, ths subjects wero young, below 30 years of ago and havo nevor worked in any other Industry, Pre-employment medical and dctailod laboratory examinations wore carried out in order to provont tho hiring of those who would presont some cor.truln-dlcatlons. Records wore maintained in the personnel file for each employoo of tho results obtained In the courso of routine medical examinations and on . tho occasion of tho thorough examination, clinical as woll as laboratory, dono annually. In addition to the medical examination, the following laboratory analyses wore dono: Dysprotolncmla tost Electrophoroel* of somm proteins ./ L5? hepatic "clcarsnco" Cold proasor tost* Digital plothysmography in cortaln ct*oj. , \ g. ^ RSV 000^638 - ft-?-.. canes that exhibited clinical nervous, digcstivo, cutaneous angioneurotic manifestations, were routinely hospitalised m tho cltn.e fdr occupational disease* in order to carry out tho cosplox laboratory testa and to establish therefrom, if po*xiblo, the causo of the intoxi cation. Thereafter, it was ncccory to cxr.mino the clinical manifestations and thc}rcsult* of Dio tost* in order to characterise Dio clinical picture and to Xoivm.ata proven Uve mvash row * : 3eslts nnd Ductission r. , Wo hnvo observed that at firm contact v;u iiio poii.on, oost frev, at tha time of changing tho cliarjes, ticrlr,.; or..;v.or leakage* cue various causes, porticularly the nervous sen*:vstctior.s apT'carcd. At 3 months; ,to 1 year of employment, dxgostiva d i > iu'uir.cos were added t o nervous disorders. In certain eases, the nervous manifestation# char, into angioneurotic manifestations (Paynaud syndrome); finally, ir. oth,cr eases there was sclorodoraa or chemical dermatitis. At V.mcu, all t.koto disturbances appeared at the some time (;,cc c;....c;l observations). In order to characterise this clinical picture core clearly, vo ;r^ presenting the objcctivo symptomatology ousorv^u in its incroniiing o.*; J of disturbances, so that tho physician any rcec-,;;.. so this intoxication m-i froo its first symptoms. Wo are dtmcriiimj i..ce with tho frequency found i for tho various clinical manifestations >, t/..i; their significance msy bo Appreciated. In tho ordcrof oppoaranco of tho symptomatology produced by vinyl chlorido, vo shall arrange then into tho following groups of aanifostatioas: nervous, digestive, angioneurotic, and cutaneous. / Xervous Disorders Certain workers stated that at tho first exposure to the monomer, or vinyl chlorido, the first inspirations have an agrocablo taste which they -could not define exactly. This is compatible with tho opinion of Sable . (cited by Danishovskii) who stated that the monomer, or vinyl chloride, has a pleasant ethereal taste, and with the opinion of Lazarcov (4) who holds that -i this substance cannot be tasted except at narcotic dosos of 7 to 10%. After several inspirations, a euphoric stato sets in; 11% of tho subjects sing, whistle or laugh. (Tho euphoric stato and the pleasant taste persist for only a short timo). Host often, during exposure to the poison,-ho subjects experience a hoavy feeling dn the legs, are no longer ablo to coordinate movements and become dixzy (47%). According to then, this state is similar to Alcohol intoxication. Those disturbances occurred most frequently in tho courso of tho manufactur f ing process, at the ond of the ehargo, daring the discharge of latox, as at other times when tho mor.omor Is roleased in concentrations as high as, according to ?ctro (9).j.v&Ts"mg'.^a^whieh is greatly in oxc; of tho maximum pormi*.ibl*. liViVof 0.03 mg/a37 U-T hr Translator's notot (applicable to Romania). I '^l-jSOOag/m3, or 300 ppm*. it/ Zr. tho VSA, tho 71 is RSV 0008639 /iff-. A Subsequently, in <fi% o( the r. sonnolcnco tot* m, which awnlni..aiL. ilaruwic and can occasion work aec * ;; t* . . After * stay in tho open air, tho syi;p;.oa* dlcinlshvprogrosaivoly, then disappear. \x In tho cose of 6 workers wivo were engaged in tho repair of certain defective parts, coaplote narcosis sppcarco, which disappeared after they were rcaovcd into tho open air. After a porlod of icvorni aonCtu of worklr.j in this or.viror.sent, a e`.';o of esnolonco porsists afiwr working houru, At hose, tho subgoet* exhibit A hypcrsoania, sleeping between & &;.u i-i hours a One pc.'*or. vith a brief interval, continually for two days. Tho sloop is deep, without drcans. 7roa this point of view, particular attention must bo paid to r.ight 'fork, because tho vorkors could oasily fall asleep at tho work s1 to. % When there <.a an abundance of vinyl chlorido vapors, there arc cosplair.ts of formication of tho lowor oxtrcaitios followed by a sensation of hc-t ovuf tho ohwiro body. $ineo tho cono&er vinyl chloride is lighter than air, it could bo that it acts directly on tho integuoent; this would agree with tho opinion of Danlzcpskl (1). Arforexle, attributed to tho toxin in 23% of tho casos, sots in rapidly. In 12% of the esses loss In weight of 4 to 17 kg. oceurrod. p . After repeated exposure, headaches arc reported (36% of the eases), nervousness (5%), faulty aemory (3%), insoenia (3%) and a general asthenia (7%). '* Theso syoptons indiceto tho astablishccnt of a neurologic asthenia subsequent to aore prolonged exposuro to tho Poison. . Vo wish to point out that in sost of tho eases, vs havo obsorved theso clinical syaptoa* without considering the signifloanee, of the resistance of tho organises. In general, after the first syaptons, protoctive erasures for tho vorkors were instituted so as to prevent the appearance of acuto intoxication. According to existing knowledge, it scobs that tho poisci has a sonontary narcotic action,even after ropoatad exposure. In certain cases, a neurologic esthonia sets in. Digestive linnlfcststlons* ^ ii Aftor a variable period of tine, in the courso of whici> tho nourologic manifestations predoninato, digostivo ayepioBe appear. t J *1 *** 00086^0 .j -The first symptom which presents ltxcli* is anorcxii {i of the e~oo./# .Tills indicates a general intoxication. Subsequently, vertigo appear* V- id of tho eases) and, soro rnruiy, w{jvu,i. .Laser, pains In the opigniiiric region follow flCfc of Y;c case*/, i feeling of discomfort, of hcawnch*, of pressure in the right hypochondrius * tho cases) or of the left liypochonuraum (0% oi tho cases). T*o patients present pains, oi the bori.-.g typo, which however do .'.os a**uac tho nature oi pancreatic attach-. /a; express p dita*to for f-ia. * Upon objective examination, ir. oi tho car.cs, a hepatomegaly without Icterus has been cst.*.;>lishcrt. The liver exceeds by the costal border 2 to h-ftnner widths without a lowering of the `upper Halt of tho liver.- Upon repeated examinations we i.;.vo fo..nu that tho border oi the llver has an elastic consistency, then become* harder and acquiree t.w consistency oi epidermic hepatitis. Vc have iound that 6% oi the hepatomegalies bccaao liter complicated 'ey splenomegaly. Alter removal from exposure, wi-,,iout other treatment, the hepatomegaly regrassod and in the major* ty o.' the cocos, tho ovorall Condition becomo. normal our observations show that in cany cases hepatomegaly dovelops without Any association, wlth tha digestive symptom*. Vc'have observed tho fact that ir. 5.3% oi the cases who had formerly . cxporiencod epidemic hepatitis, the hepatomegaly had appeared soro rapidly, < although at tho time of their employment in cho factory, tho liver was within normal limits. Tho enlargement of tho livor pointed out to us tho difficulty of or. . stiopathogenic interpretation. . j Tno question arose of the diagnosis of toxic hepatomegaly or of that * duo to anicteric virus infection. This is why sost of tho patients afflicted with hepatomegaly were hospitalized in the dopartmont of occupational dlsoasos. Granted that: the hepatomegaly appears after repeated exposuro to the poison; tho border of the liver la of soft and ur.ovcn consistency; ^ the hepatomegaly disappeared after change in work without othor treatment; it appeared in a group of people who ware subjactod to treatment by injection and among whom there were cases of epidemic hepatitis; in spito of the absenco of theso xar.i foatat ior.s in the other sections of tho Industry, it had not boon supposed, at first, that tho enlargement was -Of toxic nature. a TV.o hypothesis of so occupational origin is favorod also by tho fact that in pationts subJoeted to chrome intoxication by load or morcury, beforo tho RSV 0008641 1: rt- - * L- ; .a > establishment of attacks of developi.,; illness (lend colic*;} vo cer. w 4 Similar hepatomegaly which d;sa;>pc;..'i, afio.* treatment with ,`wVA (!(/'/ Laboratory tegti carried out by us woro: a oleetropUorcsi* f sorum protoin* thymol reaction % sine sulfate tost bromsulphaloln (25?) tost, one liver biopsy. Electrophoresis of sc run proteins (soo Tabio I la Appendix) shows tror.j tho 3o eases with hepatomegaly; . a diminution of albuain, below S3: 11 tisos; * an incroaso of moro than * 5% of a. -globulins; A 9% ofa^-globullns: 10 times 20 times 4 13% of j3-giobulins; 9 times 21% of Y*~Clobullns: 10 times. This shows that tho elcctrophorotic pattern is identical with that of viral hepatitis - la which principally the Cf2-giobulin is increased. Vo noted that tho thymol reaction, the'zinc sulfato, and the Crocr.stcdt testsworo positive only in 6 eases which shows us that In tho determination of tho disturbances, the electrophoresis of scruo proteins is of particular value. * Two esses of 11 showed a pathologic change in response to tho 33? test, .indicating that the liver`lesions are not localized in tho parenchyma. Since we hAvo found hepatomegaly without protoln changes and with a normal BS?, ono might be led to boliovo that tho poison produces a transient congestion of the liver, identical with that demonstrated experimentally; this in turn shows that the hepatomegalies which we have observed are of toxic* naturo. * As a result of repeated intoxication, the congestion can chango into a toxic acuto hepatitis, accompanied by electrophoretic changes similar to* those of viral hepatitis, and finally, those lesions car. bccomo chronic. In 2 cases in which hepatomegaly persisted for moro then a year and in which the border of tho livor v* of firm con-iaiency, a livor biopsy rovealod tho picture of chronic hepatitis. --> i'v RSV 0008642 ni; #< Mstss* Among 20 paiiontx with !A*Ct between 0.73 fe,;. p ;,;u i .:; iy, the to;*w;i aidol.^o wan four.;. O -- 4* III / Ciitiv'u vii..'*, wui*V<i' A fact to bo kept in mind is that we have also found a tsodlf iCdiior. 0 the protom metabolism n-- wor.^c-* axpo*eo to tivo toxin vno wo/o not with hepatomegaly (see Table 11)* C tho 26 caso* oxasined, o found: an albumin lovol lovor than 53%; ic ti,cs. An incrooso of oofo than 6% or <t -;;lobul ino; 6 t.mcs 0% of C,-.7iobul in* ; 10 xiu.es 13% of p-.iiobul i;\ : 3 tinea 25% oi y*-,;lobul in*: 3 tinea This shows us that disturbances of U;c protein metabolism ear. precede hepatomegaly in eortain coses, and that tho poison sui^vcionciy influence*this motabollsm. Therefore, tho hepatomegalies that wo have found aro principally of toxic nature. At first, they are in effect congestive, and later they assume tho fora* of acuta hepatitis, lccr.ilcal with ar.ictorlc viral hepatitis; eortain onos of than can bacoao of chronic nature. Vo wish to emphasise the fact that tho disturbances of tho protoir. BOtabolisa can appear in certain cases before tho onset of hapatomogaiy. Our investigations show that electrophoresis of serum proteins and determination of aldolase activity are of greatest importance in the bio* cheaical diagnosis. ,, At the last examination, in 9% of the eases, s dyspeptic syndrome of* ulcerating type was demonstrated, although we were unablo to discovor any radiologic changes to this effect. In tho knowicdgo of the predominantly narcotic action of tho poison. Is sore probablo that the derangement of tho cortical dynamics after repoa exposure leads to s disturbance of the dior.ccphalic centers which comes into play in tho pathology of these manifestations. Vo continuo our observations. Angioneurotic Manifestations These wore domonstrablo in 6% of the caret, in tho form of the Sayr.nud syndrome. . (Distribution as to sox: 3A. of th-j c.u.oo worv *;cr*.l Vo Bi,ght mor.tion the fact that m 3.o7, of tho caioa with Raynaud's syndfomo, there was also scleroderma and hepatomegaly. RSV 0008643 Y w * Z;\ order to illustrate the clinical picture sore eloarly, we wish to cite the following observation: Case 1: W., male, aged 23 yonrs, has beer. er.;:r.*cd for 2 yoars m tha process of poiymcrisntion. Paaily and poror..*.l history, normal. Sachas lw to 20 cigarette* daily. MM the beginning, the patient observed that during the release of toxic vapors, thcro was first a euphoric stave and ther. a state similar to inabriatior.. ..*t Homo, ho slept bvVtfuwu b u;.u !; hours u.-.vly, , At work", his hands immersed ir. tii.r hv.i-x, v'ult formicr-Cion, numbness, and then a sensation of host. When the oluvior. w.-.a white, he observe- a coloration o: the skin, in contact w. th cola waver, it vas o'asorvec that the iir.jors'oecaso pale, then red ana cyanotic. Concomitantly, tho same phenomenon appeared on tho jrcat toes. This occurred also upon exposure to cold* air. At tho sr.ac timo, ho was affeeted by persistent edema of eyolids, of tho * face, the neck a*.u chest; tho skin became flossy, the nails "unovon" and the Xaco assumed tho appoaranco o a lull noon. 7roa tho clinical point of vlow, a Tlaynaud's syr.drosic was ovidencaa, hepa tomegaly with sclorodoraia of the face, neck ana thorax, even of the lover and upper extremities, but particularly of tho finders (dermatologic examination mada by Dr. Capusan). Musculocutaneous biopsy showed typical change* of doraatonyositis <Dr. V. V. Papilian). Tho plothysao^raa showed significant inhibition of tho vasomotor cor.ters. 'K In addition, tho urinary 17-kotostoroi.es waro increased to $.5 a;, in 24 hours. Tho lunar facies made us think of a thyroid insufficiency. Tho iodine . uptake confirmed this belief. Tho dysproteinomia tests, electrophoresis of sorua protoins and tho So? test gavo normal results. By .Its narcotic action, the poison produces first cortical Inhibition;* then appear tho disturbances of tho diencephalic centers, principally tho vasomotor and metabolic disorders. Tho symmetrical nature of tho vascular disturbances, tho plothysaojraphic changes and evdn tho tissular disturbances and tho scleroderma vouch in favor of. this fact. Tho thyroid insufficiency, ovldor.ecd by tho iodino uptako, shows that tho poison has olther a diroct influence on tho thyroid or an indirect or.o via tho "hypothalamus-hypophysis," which producot inhibition of thyroid function. After removal from oxposuro, tho sclorocoma and tho vasomotor disturbances greatly diminished. RSV 0008644 ' *r *tt half of iao cases, '.;/ showed an inhibition of the Vasomoior centers. A* to ;.ic u;r.,; .::.su.,, i..o rclal'.cr.ahxp.'i r?v norma. Especially lit ihe camc i.<? plc-hjr.-.y va:. normal, 4 **;o disturbance;! L isappcarod completely .`icr removal .Vo- voxxc k ; exposure, but u\ th rest of tho cn*c, they greatly diminished, which vould indicate their connection w;tu the toxic environment. K'U : T..V 31f> A* concerns the changes In artcr.il tor.^l. a* *cll as tho binxsa wore core loan 10 to 10 . Cutaneous Manifestations VO tou.-.G net tno max: below r.orti 1 Viluos. \ Pruritus, vhic.. was found in <.6% ox the eases, without hoing accompanied by skin changes, was tho earliest symptom. Hater, two different categories of eutanoou* narvifcstitions could appear. Tho first noted was contact dermatitis, then scloroacrma could be observed. . X* Contact Dermatitis (4,4%). On tho face and hands (uncovered parts), pruritus followed by urticaria wore noted. Papules, microvcsiclcs and largo vesicles appeared on tho face and hands. Tnero were esses where tho aicroveslclcs and the scabs disappeared spontaneously, but in othors they wore torpid and, after return to work, they reappeared with intensity. Case 2: X.I., chemical technician, 28 years old. According to his . personal history, he had suffered epidemic hepatitis in 1042. Since then, ho has hid frequent anginal attacks, lie has been working for a year and & months in the division whero sodium acrsolato is mixed with different substance^. 'In December 10<30, micropapuics ir. plaque-fort; appeared on the forearms And face,-then sicrovcsiclcs, scabs of which remained. Those eruptions wore pruriginous. Upon hospitalization in tho department of occupational diseases, zones of nicrovcsiclcs ar.d areas of scabs ware noted on tho face and forearms, as well as large vesicles at othor sites, which . sftsr opening, loft the skin covered with largo scabs, . Tho vesicles contained a serohemorrhagic secretion. Sedimentation rate, 2.4 na/hour. /3 Leucocytes 5,000 per mm of which o sonoeyves, 6% eosinophil*. 7o% wore polynucloar, 1C% lysphocytos, Red cells: 4,C00,000 por mm3 Kooogl'bbin lovol; 02%. Piothyscogrophy rovoalcd an inertia of tho vasomotor cor.tors. RSV 0008645 i-- Chanjo in work brought complete disappearance of tho dermatitis 2. >eldM<;gyaa (3.0% of the caiwa). In tho course of work, certain vo.*.i.rj note ;. plcaunr.t odor, followed a tlnot by ODo*on<>> &! -c t w ' uii.twi`o.....w.;, <*!. vw<>ul<.r>hv which, ir. tho cr.ac of *o~to, ',>orai*U ufie.* .ho cad of the worker.- day. Other* report foruicatxon and numbnott* of tho extremities. Case 3: T.2., a;o 20 yoora, has worked far a year and 3 ivonthc at tho autoclaves. lie ho* worked at no other n;c. 1'^c.lly and personal hta.ory rovoalcd nothin; remarkabio. After a year and a half of exposure, diffuse pains developed lr. tho lower ana upper extremities, with cue;-... They were interpreter. to be rheumatic pains and treatment brought no relief. An r.myjdalcctosy was performed. After return to work, a generalized pruritus developed on tho face, nock, cheat,the abdoaon and tho extremities. .i Dermatologic exanination (Dr. Capusan) revealed edema of the eyelids, * f face, with disappearance of ridges. Vha skir. over the abdoaon and tho el.oat 4 could no longer fold. fc* .On the face and chest, grayish spots wore soon, that sorted together jar. 't t as in tho caso of chloasma In pregnancy. This clinieal picturo was Interpreted as scleroderma. The liver was enlarged by 2 finger-widths. Tho Takata-Ara reaction was . faintly positivo. The thymol test yielded 14 units. \ Tho proteinogram showed: i .- total protoins: 9.6 g% * ' albumin: 48.7C% C^-globulins: 4.85% jOj-clobulinr: 10.50% 2-globulins: y"-;^obulins: 14.70% 21.20% Consequently, clinical and laboratory examinations dcsonatrated tho prosencoof toxic hepatitis* . Too latter ststocont appoars to bo insufficiently.supported.. (Translator'* note} RSV 0008646 ^ t The t0 titer showed norunl *c.hw'*u (1*0 w of aniiaireptoLy-ir. / ^VtMiy^mOjn'nphy evidenced n suxrkcct tie;>>VNJi*un of tho v..,.og,o.' c*jnt'-;\. / i;ial did not respond to *;i*minWoi<. Vhra'u to-; skowen u.\ ;s;.iw.;.w. idilution and concentration tot ;;.w0 normal re*ulta. * .dynamic activity of protein# was noruai. T<io iodino uptake tost indicated hypo; ur.ct ioninj of tho thyroid. Arterial tension was 14/7 ca ll*, fc* Urino was normal. *n this case, as a result of :;>o.u;ru t/.w poison, diciurbnnccj t5o vasomotor centers .*; o v.. c (change.*. in t.`.e protolnograu in the dysprotclnc-.ia to:, t) developed. Thyroid inuffic.cney and chronic hepatitis woro found coacoaxtantly. iinstromattco statos that in polyvinyl chloride intoxication, a thyroid ; insufficiency exists. 2* is intcrosting to noto that in this ease, m tho period of ono year tho time of removal ;roa tho toxic environment, tho scleroderma, tho vitffjir'... Itaynaud syndrome and hepatomegaly have disappeared. Tlx is proves that a toxic source was connected with tlxcs phenomena. In the casoa of scleroderma, the majority of tho subjects presented a thyroid lnsufficioncy and an inhibition of ihu vasomotor centers. In 3 eases a dcrmoauscular biopsy was performed, which rovcaied chronic dormatosyosltis. In ono case only did the manifestations of scleroderma fail to regross after removal from the working environment. In the other eases, these symptoms disappeared,winch substantiates for us tho icca that theso changes aro operative in a reversible period. V Tho manifestations of the scleroderma, acccr.par.icd 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 of the hypothalamus. Tho participation of`the thyroid in thoir production reduces the problem of this thyroid lnsufficioncy to 2 eventualities direct action of the poison on the gland, or consequence of thyroid innibitIon of central origin* *. > Tho manifestations of collagonosis, verified histologically, which occur in- cases of intoxication by narcotic substances, reveal to us that in the .pithagor.osis of collagonosis there occurs at first, in these eases, a disturbance cf protein motabolisa duo to tho activity of tho central nervous system and followed by tho appearance of an endocrine dlsordo r (thyroid lnsuff icioncy). Tho roversibility of tho disturbances indicates in our opinion that* there is a poaeibiliiy of recovery if i,;io.,vv..tion tuko p*aco in t.i initial phase. * .-.Jj w !M*IU J "i rSV 0008647 \* ^ "" W C.'iicn of coll.\gci\Qai,a a i v cr m u4n;;on of h',*d-/;.nir.7*hi Oi* Otnor sub*c.-.i.ccH whose notion la prcbi/uina.iwy oa thv coal*' *ioa arc described in the livornunu. Yh*: would co.u'ir- out4 tions. ** i)wiUt Vu" a5 a result of investigations into the environmental conditiona performed by hygienists and physician*, rccommenc-ticns were formulated -or ;ho protection oi the workers ;.nd for leakprooflug the cq U t -n spite or these ecasuros, so;ao c.iwco of the (i.(.c..uo i;ve occurred during the past yoar. Thanks to tro&tuent instituted according zo the indications of repeated clinical, exittoinaiiono, and removal i'ro- who working cr.viror.scr.t, we ;.ivy succeeded i; controlling tl.u oidcut casc^, g.von that thoy wgro undertake;; during a period of rovorslblo disorder*. Tho recognition by ccrtoin physicians of the oar. ifes tat ions that vo ha vo Just dosenbod has permitted the detection of intoxications f ran tho start, and thu institution o adequate ccasuroo of prevention and treatment. coxchus;oxs 1. Vinyl chloride and tho vinyl monoaors possess a narcotic action and produce, depending upon concentration, in addition to characteristic neurologic naniicstatlons, a stato of ouphoria (12%), followed by a state of inebriation si&ilar to that of alcohol intoxication. In cortain cases narcosis can appear. * + Ait or leaving tho working environment, a stato o1 5osinoler.ee (43%) . , porsists, with hypersomnia. Vinyl chloride acts on the skin and produces a sensation of fornication' And of heat. *. 2. After repeated exposure, a neurologic asthenia sets in In which t * somnolence predominates. .3. After a variable poriod of tine, dyspeptic disturbances aro added to.tho neurologic manifestations; these are at first not character!*tie; they arc InT' ^tho fora of epigastric pains (16%), swelling, discoafort, fooling of ' 1. heaviness in tho right hypochondrlum (7%) or tho loft (5%) with anorexia, * particularly for fats. > In 30.3% of the eases, congestive hepatomegaly appears, which nay mimic toxic hepatitis without Jaundice; some cases may become chronic. Xn 6% of the casos, the hepatomegaly is accompanied by splonoaegaly. Tho protoir.ograo and tho aldo--acos aro tio - o,>t aonettivo twjto and s;cv cnangoo sisilar to those of acuto hepatitis; ir.croaao in w-giobulir.a and of tho j- and,* RSV 0006648 I 6^98000 AS* \.` 596T *91 jteqneaCos ** Xloqde^O 'H ! Xq p*cT*uc.ii WTa*i*o?*q* otoqi ;o N0 9-tPn?o,T<! o~i u? s^rtf tr ppXrt<! oa?y o'oirouos xXuta qa puo op^zo^^ro tXuta act?* *eAt*T?c*p on v.?.o\y oa?^ '^.to/% ,to cTurtp pu? oo.Tncooo eAxaa.xtf ;o vxamx**vx c ,* rorro ovs ?o /zT-*o7ova *.:t r:-yo.roo(ftfosTp JtToqa puo 'TunoX X'dajzctoj: >r-v- rr C^p o'.;a *,:?T'ppATpuT T --.toy :?t *uo"?,t ATp uTua.too u* puo 'paused Tc<*oao* ;o 0*5* -a-P ^*ul v~ -* s-oTic;c o jt u cv: {f3v5 ;o ??v!vjoW auonbo.r; puo uoppn* c*i^ (uat.:epo.TP*os pvt p-oo.tpu^s tpneuXr") wvjo ova uj poonpoj<fs>j oq aouunP *,*.* u*:rs '.to ito^'.C'S s?r???:') so* op sno.toionu vf sncpoq /Tox^Vtotf Touoxa inooo U5 coyPi2ut-*s:5 aoo.ti' ;o c-c s-'vupvr; /Ijtoav/.ooox P'JC icsfutt? i*j, *l r.tf^e^oOf puo #opouo o'.;i pOAjptq uoor. ooq *SC**C vx Btt *2ct2,top ^Suo^o 'vota^ppo \I* ,r-- ' 'OJOIUOO joiowovoa q> *p vpta r^rvur vr *too vt to ;*': v-.' 'tMO'tr> /:c'v.t:'v:*/tpro^t! *uow IfunoX 0*^1 Juotsp c?-*otICc tw: eao.tpu/o pnouXotf oqa torpp oqj j *9 uj *a5o.TTvc oosoooq ooSuotp pt*T05poj anoqa?* Jopt** o *oP-.^Xa esojpuX* oopvp .y. .o *JT oanood* j jco/ c aaajY "> > no ov''/ o*.'i puo !0*2 0CO.t "*.*'* : .* T X*V PATlX^Otf PJt?' OV:u.O,lJ) *5W jOWXtr* If* ;*UTT^!OT^~-n . ;**-- . - , - Is - Ma f : :3r V- -sL . araiTOGSArvry. X- .OAtvlshcvikli, S.L Ejjovrov, X.X. 1. DA>:rs";,rs:a i. s., rcop.cv x. Cl^* !T'4d& pro* SuOo*ov, x9^-, nr 9/ p* 2w# 2, FILATOVA V. S., ?GLOKC.\GVA L. I., G?.GXZ3IRG 7. . Ci^j* Trudii^ 195^1 nr */ p 6 *3* GABOR S. PtOblfiiTiO cd *2*CHo sunc*A In AncUjwnc vOrduwOaOr p*2ww*cci^ CoiTiUiii.cro *a \#ori*or*r<u4 irwC*vc^i.or>blt A MitducPr^c c'Vm*wC^ '.' Cluj, sopto=;brio/,`196l. . '. ` *T * 4. LAZARLxV V. s. ' 1*. il- t SuosvanwQ cnln*CQ noc^vo In jni^usv7X3, vox* x,.xc*, w>#, U Bucurasti, .1954. 5 Vi'lr'ttriO: O* *'--. xgiena (Bucurssci), 1961, nr, 2, p. 97, . j 6. XAXTA X., XURSSAX X., SIR3U 0. . Unela aspects ale tulburarilor hepatico detaminato de niGciul toxic la siuncitorii din Industrie chi;aica, Oceanic ara* la .. S.S.M,, octocbriQ, 1961. - * .\ * 7. MAS73CKA7720 E, FISCHER A.K./ CRI57IE; K., DAXZIGER. ' .*: Anar* industr. Hyg. Ass. "Quart., I960, vol, *21^ nr, 5, p. 394* . ' $. KASTROWTTZO 2., FISCHER A. K,, . C3XS7I2 H. 3ull.`OIT# int. Kyg. "publ,, 1961, vol. 36, nr. 3, ? 244, 9# ?2TR2 x. Csractorizaroc 1j*cnico"C4...-iw. - ootir.orca P.G.V., Comunxcaro la ` '.. dc r<<r.c0. .w octonbrxc, ,- RSV 0008650 V v H>iuXwH c.# $uc*y i ?*S--v.vw v., Parris x* Corcocsri chinvlco-fiziclo^lcc si. i^icr.ico-s * rbricaros ruvsalor plastics scri.li.co el vinlliccj S*St*u/ ivulO| 1962* -iw: : _v. ' ' *r -. k* rTr^!s* ssrsH 4; xz?.v: Arch. Xal. prof., 7.20, r.r. 1* p. cl, 1559. l>=- "IO AitWft ^ f Aspects toxicolojicuoc .do lTiniuscrio das zic.t-i.ircc plc.cci.cucc Arch*: Xal* projT# 720j sir j.j p. 4-1/- 1959* 9. 1. ** *. .*;* i /,.' * ` * . - : * % it a : t * *. *' / - '*. 1 . . , *, 1 *.% * RSV 0006651 r <vo. " v:'rN r-;vv.x` I? ki c; 4,4 I * * ft k. ;c. v. v. i : ,, i&:*,7 4 4,.'. *.: sm.* i ,243. .7 I ( t9 i* ;' .* *. rs ` : . *. v. ! i>. ;. ! v. x. j 7 c ,v k . i* ?' Iti * *ta*Vt:. J1\ S', s. n 1 X, S. 49,'ft 2ai>3 3^il 6t.3 . .is.s I. 5.23 [ -A,.;* *7.77 3,13 | *,75 :b,5 l.uv , ;x4u ; i2. i: 6/,.: : .? 7 i i|*it | * :s.:3 Ji 2:,:*2 . S2/i3 ! 1| ,** i A i 2 fM o** 32 . *s * c;< a-.*.** 4* ?4 V. >.. V. 4,-(A 2.31 7.;s ; i2.*9 i.tM i *..*. | . ..3 1 J 1 2; 2i ,, 1>rf at. 3. 63.31 4.K6 7.:c t J..31 1 ::,27.! * s.* , 17 ;x '* 2u 2i 33 2 s\ v. <* K. SC. ' I- s\* U. N. A. V. At. :. C. 1. 3>,h l 32.S* 6:.<*i 64,2 63.r,7 S.*,4 3.*. 5>4 3.S 4.^4 4.25 2.73 -i .*. . 7,C!3 iZ.KW 6.52 ! 13.43 ' \ o.. ,* 10.23 1* S2.J7 "* 1..5U ' :o.^3 | i: : * ,2 r '; ! 2a-.,23 1 H * *4 . . . .*.*. . <o ' ! 1* t r? # 1% V. 6 3.1 X.. 1 ;2.:a ! :3.*-x ; 6 ' ? ** > #6 27 0. 1% V. 3. 1.32 i ;.:.a 4.X 4. * 13.2 12.3 . ; ::.i : **V:3 i* f ` * * 2* 27 II, >, 6i7fe v. *. - 53,13 * 4.5 . ta.i * 6.26 J ;:,i; i *:5.: , ' i * j 2..,a 1 ;. *6 * t 2M . r. it. ,si,ft; &- , lv.:2 J2.C i 2...71 J *. at 3. c. f-'-.ui j 3.6 341 * ' : i ' 22 N. 1. <*,i 5,56 .-'.5 C2t*5 . ' i V* 1 23 4 34 33 30 37 33 30 :. . ;v. c V. . V. V, C. 31. V. A. 57 42,7 66 59.1 S3.ll 54 67 3.3 o.:a 44 3,1 3.X 34 3.6 7.JI 13.5 6,3 .^e jo.: 7,4 6.2 :i*.5 5 2: ` *4, / 1 * t *4:.xi j :;,< ! 3*`.55 '. i.7 1 i*.7* ! :2.; 1 n i a.c ! :y ' 1 12.6 i `sa.x 17 * - /. ; * 5. 43 * H * , V . < L 40 X. . M. i . .. 6,11 . 10.2 <2 1i 24`31 11 * -- - / ' V| , .< Table IX. . Aceulce of tx&aicueion* of voricaro without h?&;osesely. >';C. **/. ! ' *I * - i. A No. Subjectj A.ouai.-^ ..VUJ'-m Cr^- i d-. T-.. 4 Y. V. -- * To ^ * ^ -. * '1 JJ. ,V X. c. 47 47,26 6.7 ' lfl.-s *4,1 ; li.i'ji 6.7-: 10.76 11.23 2-1 .AS 4 If. Ji. 55.97 . 4,97 10.10 j;,99 /(Mf k5 CH .V. .30,03 X. SC. 40.X7 6^46 ; 5,93 11.52 * 9.72 11,72 i i,2X 22.9? 22.56 7 M. 0. A,0 2/76 ' 6.93 10,1* 1%9S ,6 ITT, 50 . 3.7 12.3 12.02 22./.X 0 i:. v. 60 5.43 7,96. J>,79 21,77 10 51. s. 62,57 4.16 * 9,95 11.23 21.72 ;j 0. A. *2,06 3,4 * .* .JO 17.2 32 13 * V. 1*. 63 6 . 7^ .S3.* * It .til *13 . n. Y. 49,62 4,1 . 6 * 13.33 * M.6 * 24 *. 15 16 7 IX x.v. w X. M. 11. im a. *56 2,71 . 51.07 * 52.t& 57,72 3,7 .4.17 4,7 r. 5,.i7 * 3,;4 ` 6,4 9.75 SI.2 1*\3< 6.7 'K x,*-; ,*2.19 :3.3 -j 17.23 17,00 3; ?\17 27.33 S3 Si, 47,7 V.7 6,.:i *, e 20 . 2: .3. 7. * >9.35 r. 55.69 **r* ii* 3^ . 7.; ;:.:a S7.fi 23 i*. r.. 4 4I|^ ?3 H . 51. >. *6.1 4 c. 53.31 4* 5.7 -,;il 1 Aa*i ' 1 .'*4 2,25 ; ^ i ;:,2 2.". M .... i rny=o*i 2r.S04 (jr.iz*'. - 5* *- * > 26 * ** t: . *.- n\- u k 0 9* * ` . * : *32 ^ 1 35 7; V jo `ca*x V 25 . so *. *Uo , * o 13 .; :* 46 ;j*r ; ia . - 3* J4 56 ..% 7 . . 35 J t * 34.'. 5 er* % 6 35 ;? 56 . 5 # , M- 1 4* .* ' /. ,v , > ;i % . M ` v *\ ,/i. '.'7J ` rsv 10008652 . ** i-. -i\ >-.t