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R&S 109529 .BIO-MEDICAL RESEARCH DOCUMENT DESCRIPTION FORM 63 68 69 76 Duplicate in all cards:--S> / 9fC year as-1961- 0=883230 File number [Right justify [Numeric only] Author(s), as Last Name FS (No Punctuation) and coden for journal as JAMA preceeded by one blank space 1 20 21 m - - hi v -jasaas^. 40 41 77 78 VC Sub-Index Code 60 61 62 11 12 13 Title of Report; end with space-hyphen-hyphen-space. Follow with Index Terms, separated from each other with comma-space. Avoid other punctuation; do not abbreviate. 12 61 ."t-'.V /u"'' Z/'1 tr'CVu hn 1! > n ; t 1 luo/ ,'d e 21 (y 4 ' oo-'17'M n nr! fc r iJ r f\ deb in ^ .t. 22 23 24 Source (Journal, Vol., Number, Pages, Date ) 12 "Z ISr. . [Joi. dr. f\Jc. (( . icH*> nnI' 61 62 31 32 Brief Summary 12 10 SUMMARY: 61 62 61 62 63 64 R &s 109530 u^00230 #251. INTOXICATION BY VINYL CHLORIDE POLYMERS AND/OR THEIR ADDITIVES V. Misgcld, H, J. Stclpmann and Sibyllc Schulte Steglitz Clinic of the Free Universit)- of Berlin, S^in Clinic P-nd Out-Patient Department (Director: Prof. Dr. H. W. Spiek), Institute of Pathology (Director: Prof. Dr. W. Masshoffj Translation of: "Zur Intoxikation durch Vinyichlorid-Poljtierisate und/oder d eren Beglcitstotfe," Z. Haut~Gcse i Kr., Vol. 48, No. 11, 1973, pp. 425-4T6 ( #251.- -INTOXICATION BY VINYL CHLORIDE POLYMERS AND/OR THEIR ADDITIVES V, Misgcld, H. J. Stolpmann and Sibylla Schulte* Translation of: "Zur Intoxication durch Vinylchiorid-Polymerisatc und/eder dcren BcgleitstoffeZ. ilaut-Gcschl Kr. , Vol. 48, No. 11,'1973, pp. 42S-436 The complex pattern of damage as the result of handling a plastic became known to us when a situation arose involving difficulties in differential diagnosis. The synopsis of the individual findings, job history data, and ..he literature on the subject enabled us to discover an occupational disease XL caused by long-term skin contact with vinyl chloride polymers (PVC) and/or their additives. Juehe and Lange [6] published in 1972 a short article on "Skin Changes of the S-1 erodermal Type, Raynaud's Syndrome zp.d Acroosteolysis in Workers in the PVC .factoring Industry" [see also [7]). They were able to show that nothing of the kind had been reported in the German literature (see also [IS]). The case histories we have chosen as examples should contribute to propagating knowledge of damage caused by a particular set of industrial circumstances in the attempt to ensure that intoxication by vinyl chloride polymers and/or their additives', which occurs today with variegated symptoms, including extracutaneous sjmiptoms, no longer escapes diagnosis -- as we must suppose it does at the present time. R&S 109531 Patient observation: Mr. E. B., Identification No.: 22 28 06 021; telephone installer, age 50, admitted to FUR Steglitz Skin Clinic in December 1972; admission No. 1376610. Case history: First difficulties about 4 years ago on the hands: swelling mainly on the left, paresthesia, weakness; continuous intensification of these SNTiptons over the years, increasingly painful radiating sensations in the hand and forearm. Two years ago, clear tendency to hardening of the thus far edematous swellings of hands, in particular the forearms, with discomfort upon moving fingers and hands and motoricity when writing; whitish finger color after cold stimulus. Arthralgia at the lower extremities, discomfort of the upper abdomen, severe discomfort through sinistral acoustic pnenomena such as hissing and whistling, etc,, with damage to the right ear and hearing impairment which had been present since childhood. For years, symptomatic treatment under the diagnosis of a rheumatic disease. / Hospitalized for in-patient investigation with progressive scclodcrma suspected. Skin findings upon admission: Both hands with tight, pronounced, pittablc edema, more distinct on the left than on the right side, andi the skin was firmly attached to the underlying tissues; diffuse"skill patches; pileous areas unaffected. Pale u h i t i sh-ye 11 ow i sh appearance of the integument ot the hands, striking. iiUensi float i on <^t the pale color tone when the fist was clench C 1 ear -1- dcrmatosclcrosis of both forearms with relatively sharply defined ramification: of these phenomena toward the distal upper arm. Remaining i ritegument and frenulum of the tongue without striking changes; in the center face and over the check bones discrete telangiectasis which apparently had existed for some years (Figures 1 and 2). 1 *\ V? I J \_ _ _ . / \-- ' " .`I K. y. T (Of, i\ 'SL \\ \ Figure 1. Edema of the Hand V,"Filch Can Still be Pitted, Skin Attached to Underlying Tissues. Pale color of the region involved, face and frenulum of tongue without changes. Figure 2. Edema of the Hands More Noticeable on the Left Than on the Right, Diffuse Skin Patches, Pileous Regions Predominantly Intact. Dermatosclerosis on both forearms. Tentative diagnosis unon admission: Progressive scleroderma: edemotous or sclerosing stagoT Disease of the rheumatic type with pscudoscleroderma in the upper extremities. Further findings: No abnormal results or values in the following: ESR/differential blood count/clectrophoresis/IV "glucose/IS uric "acid/IS total choiesterol/IS triglyccride/IS creatinine/IS GOT/IS GPT/IS alkaline phosphatase/Quick test/IS iron/IS CPK/ urine status/total porphyrin, porphobilinogen delta-aminolevulinic acid, hydroxyyproiinc in the urine/IS sodium./IS potassium/IS total calcium/IS inorganic phosphat e/V.'assermann react ion/rheum.ato id factor/AST/Quant it at ive immunoglobulin/C. and C, complement/antinuclear antibodies/direct immuno- fluorescence investigation of the skin area involved for IgG, IgA, IgM, C_, fibrin inclusions. X-ray investicat ion: Area kymogram of hcart/thoracic organs/shoulder joints, elbow joints, knee joints, ankle joints, and iliosacral joints, esophagus/ /gastroduodenal tract/excretion urogram/kidney ,\-ray/EKG/lung function test/ /capi1laroscopy. Neurological and ophthalmological consultant investigation, Patliologic.il rcsul ts : Xmuiy 1 Tie e : 1: ion: Doth hands with striated t runs luscence near t !:e joints in the region of the proximal and middle phalanges, arteriography of R&S 109532 ii * J r the hand: all finder arteries visualized only after intra-arterial administration of PriscoJ; no morphological vascular changes. Visual 1yrnhograrhy of the upper extremities: Condition of primary lymph 3J nodes more ouvious on tne left than on the r:ght, in EMG: Somewhat myopathic form of the mb' potential of the digital flexor, o attributable to the edema. (O CwJI Histological investigation (file N'o.: 1563/72; McVvGl/tunica elastica/ w /toluTHTTuT blue/ alctaa blue/Giemsa (Figures 3 and 4): epidermis with lamellar orthohyperkeratosis, circumscribed acanth.osis and [Translator's Note: 4 words illegible] cutis and subcutis clearly edematized, occasional visualization of mctachromatized material. Impressive damage of the tunica elastica with rupture of fibers and swelling of fiber fragments. Broadening of the collagen bundle of fibers and dissociation of the connective tissue by the interstitial edema. In the subeoidermal region striated zones with incipient homogeneous visualization of the connective tissue. Striking packing of individual dermal arterioles, sometimes broadened and evident homogenized media of smaller vessels, with Unbonate prominences, [Translator's Note: half of a line illegible]. There was sometimes a perivascular round-cell proliferation, consisting mainly of lymphocytes, with infrequent histiocytes and mast cells. Dilated lymph capillaries. Pronounced swelling of dermal nerves, with clear formation of vacuoles' inside them. Appendages of the skin without change. * .M j t| N .-'-S'-- ,\ \ * * x* 1 S V ' '. V r v. .t ^V .-X-/ figure 3. Fdenntited Cerium, Dissociated and Sometimes Widened Collagen Bundles of Fibers. Thickened tunica media of smaller vessels, swollen cndothclia; peri vascular round-cell proliferation. Dilation of lyr.nh capillaries, barge increase in volume of dermal nerve cords. Mavnifieuf ion \ DO. ItT..ranslator's Note: expansion unknown. P o- * -;* V. * <,V > - -v- U V; C .V. X -_ l A1 . <?> ; t I *. i * Figure 4. Increase in Volume of Fiber Bundles, Clear Vacuolization. Magnification [Translator1s Note: a 3 digit number beginning with 7, last 2 digits arc illegible]. MSR / Electron mi croscope findings: Considerable lymph dilation with a high degree of flattening ot the endothelium and thickening of the lymph (figure 5a), High degree of interstitial protcui-rich edema with relaxation and, in parts, considerable dissociation of the previously paraplastic substances (figure 5b); interfibrillar edema of the collagen fibers, no destruction of collagen (average period approxir.ateiy 6-10 A), swelling and local destruction on and in the elastic fibers (moth-eaten appearance) and clumping of clastic,fiber material (figures 6a and bj. [Translator's bote: illegible word] blood' vessels (arterioles and capillaries) with swelling of the endothelium, sporatic small perivascular round-cell infiltrates (lymphocytes and histiocytes), also disseminated mast cells, partially triggering the typical granula. Pronounced perineural and endoneural edema (Figure 7a): axon edema in meduliated and non-medullated nerves, also local destruction and vacuoles in the axon. No destruction in the myelin sheath, no cell reactions (figures 7b and c) . J i -1 A *1 Figure 5a. Electron Microscope of a Strongly Dilated Lymph Magnification of a Section of the Capillary Filled with Thickened Corium: Considerable Protein-Rich Lymph (L) with Considerably Edema (E1V) with Dissociation of the Flattened Endothelium (E). Peri- Previously Existing Fibers and capillary slanting and diagonal Fibrils. Destruction in and on the sections of collagen fibrils (KF) , elastic fibers (EF) looking noth- moderately intense interfibri1lar -caten. Electron microscope edema. At the bottom, section of magnification X 12,800. a mescnchvnal cell (M) with nucleus (X). Electron microscope magnification X 16,000. Aud iogram: December 1072 combined bilateral hearing difficulty; late 30 8 C/3 January 1975 cleaf damage to the cochleae as well. Further x-ray investigations: vertebral block, cervical vertebrate 2/3; osteochondrosis and spondylosis deformans' C5 to C7; slight degree of scoliotic O <0 U1 CO 4* false posture, slight osteochondrous changes and spondylosis deformans of the thoracic vertebrae; marked changes in the area of 1. S to S 1; upper and lower jaw merely lacunar. Or (he ed i c. doe:.u j t ar.^_j r, vest_i_r a. _i_on: Incipient degenerative changes of the spine; no connection Could be i:ia e with the skin changes. -. t ^ .*.#** --f % 1' '* * 1 . . . / -a ) ' '.''a '. V."` ' ' * . %. *1. ' Vt -. 14. ' _-7 L *f ' y Vf>.h. t* 1 , 'J r.?> .* **- _ -- V- V-\` V-:-? # y *t z f i 4 . f. -*<. 's. *:' . *-- r# . ** l"*. * \v #* tt t t w *' *** . * .. `.I . *V.< ... < i\! /-.'jV' .'v " *' ' >X / tYvA fh- \v * - x. - * ...' V >. -x. A 3 rA'Vy ' s-"-w >: :'; ;Y;YYvY; w. * v.............. .............. -A ^,-^Y. v.-.-'-.'V . K ' A.-.;'%-v-\ r-N 'V-'- >n'\ , ' v-ssV-'\: \ V . '**' . V \ ^ >- A * .l-1 , ' v -.v N> , ,v' v. \v-^ \: -o -' v^ ;\ v-." ;\ Vh..v\ V.v. A ; \ . t\*V V L \ a `-'V -- ,V.'>r. n-N l'l.-lS {'igure 6a. (Upper Rip,!\t) u.b.2: Electron Microscope Magnification of a Section of the Coriuta: Con siderable Interstitial Edena with Dissociation of Collagen Fibrils (KF) and Elastic Fibers (EF). Cyto plasm and karyoplasn (K) of the fibrocytes (F) normal. Electron microscope magnification X 12,000. Inset: Magnification of destruc tion in and on the clastic fibers (1). Electron microscope magni fication X 19,000. - Vf . .V. '.p N " ..c. T.r--1' ./ . v:; ..-p.* 1 --v -.-r - i^ - x ? A -* ' '`C *. ' 'I A. v -i " *v *' * . / ' "k * (*" m * ;.-y i>i :\V. S * * V* N, ' `I . * a. :--i v > ./'v'F^ *S y . --?;*I*''' -Y. >- >*. .7 S ' i r- r***'.^*' /' Figure 7a. Electron Microscope Magnification of a Section of the Corium with McdullatcJ (mN) and -medullated (.V) nerves: clear perineural and endoneural edema. Schwann's cells (S) are normal. Perineurally, one normal fibrocytc (F) and collagen fibrils (XF). Electron microscope magnification X 16,000. Tentative diagnosis: Edema or dermatosclcrosis of the upper extremities, of unclear etiology. Job background: For the past ten years had been laying polyvinyl chloride (PVC)!^ Seal ing the pipe with thin fluids' (PVC glues containing c.g., butynal and tctrnhydvofuran (Tnnvit glue made by Henkel). The glue was applied with a rag held in the left hand so that the glue flowed more intensively over the left hand and forearm than the right, and a layer of adhesive film accumulated. After work, this was removed cither by rubbing or with butanol or methylene chloride. \ Final diagnosis: lutoxicalion by vinyl chloride pol^iers and/or their additivYuT ' 4 2tT,r-anslator's Note: expansion unknown. r. , I . t\ ;; - : -- ; f1 '' -- ' *. **.#v*. #, *#t* * . . w r- 7 ' *'.\) * ;> -- : *'*' . ,-r. ; r.vr; - - ' .7-: / . v* .. 1 *-7*v ;*//' > C/. ` . .p * ` J ; :^ k -* <i ' ' /-'V V\ V. . V . / f. . #* * ' : . * * ', * j. ' i- * ', / f # *.r '. ,m i - / *A Figure 7b. Electron Microscope Magnification of a Cross Section of Non-medullated Serves (N) of the Corium: Local Destruction (t) in the Axon and Marginal Thickenings. Electron micro scope magnification X 40,000. V-'-' ; /* * *.* c.. ' . lr - '%'' (, ' :* ------ *V ' ' .. / * > H.i i x.; * / .v rn. 1 .... : r< i ,/ Sf -T. . V'.-t:-.^ `` -J v.tT' . *'.*--:-- ------------------ ~L Figure 7c. Electron Microscope Magnification of Section of Non-medullated (N) and Medullated (mN) Nerve from the Corium with Axon Edema (t). Myelin sheath (My) intact. Electron microscope mag nification X 26,400. Epicrisis: The 50-year-old telephone installer fell sick about 4 years ago with swelling, paresthesia and weakness of the hands, especially the left hand; these changes became more pronounced in the course of time; painful sensa tions appeared in the hand-forearm region; tendency to edematous swelling leading to sclerosing; fingers turned whitish when scratched. For years, unsuccessful attempts at treatment with the disease of a rheumatoid disease, admitted for in-patient treatment with the tentative diagnosis of progressive scleroderma. When he was admitted to the hospital the skin cha.nges showed signs of the edematous and sclerosing stage of progressive scleroderma, they also pointed to so-called pseudoscleroderma [5] with various basic conditions, e.g,, a disease of the rheumatoid type. The laboratory diagnosis and morphological and functional findings, taken on the basis of suspected progressive scleroderma or rheumatoid disease, ruled out the tentative diagnosis pointed to damage by vinyl chloride polymers and/or their additives on the basis of job history and pertinent literature. Discussion The course and symptoms of the disease of our patient^fitted -^^to^the variegated clinical spectrum of poisoning o> _ ` J , j- . with gathered from the Utcrature on the subject (probable) depondsnee on factors niac.., ^ ;.'rk, changes (Table 1) functional (Table appear Kiel, a specific set of sub,octavo 2) anj oorpiaoiopicul changes ,( an os o s ^ acccetuation rules which arc and for overlapping of indnicual , ,PCS i.e., ascribing them to not initially clear, '"borvcct . aa;l oats o^th^ch.ub.es, ^ ^^ ^ a rheumatoid disease or piogiwssi\w (.w. jfound in tlie case history ot our patient.i precainIetaasceliooulfd thbee ploonienteldesioounts thiaarc.t, m.,, p ] it- "* st)lilellXt vunicacll llo/'clilaMti,oM;n.. 0l.al nei d.-.MHn-i' Y'-'b W uvint 10 o; U``jj v-ra\- examination from the nosology ot diabase groups) ma> I'l ^'M`,AlLu \ inti fami 1 ia'r acreost eo 1 ys i s , the id iopat hic.nl ly untrw.uliar acroos t co > , , and ' R&S 109536 -6- i ii fr.mi liar osteosclerosis with acroosteolysis [9, 10] and should -- after precise analysis of the clinical symptoms and the course of the disease taken together with job history -- in the future be classified as occupational poisoning. TABLE 1. SPECTRUM OF SUBJECTIVE SYMPTOMS (Almost exclusively in the arm and leg regions, and very little in the shoulder girdle) Sensation of cold Burning, tingling and feelings of numbness, weakness and tension Arthralgia,..pain caused by pressure, various pronounced sporadic painful sensations . Also: Discomfort of the upner abdomen, hissing in the ears, dirtiness ________ TABLE 2. SPECTRUM OF FUNCTIONAL CHANGES (Almost exclusively in the upper extremities, not always bilateral) Paling of one or more fingers (dead finger phenomenon) After cold stimuli, when clenching the fist, or in particular positions of the arm; Raynaud's syndrome or Raynaud-like syndrome Spontaneously or after cold stimuli Movement impeded Spasms of the hand arteries and/or brachial arteries Also: Visual impairment, liver function disturbances TABLE 3. SPECTRUM OF MACRCMORPHOLOGICAL SKIN CHANGES (Almost exclusively in upper extremities) Moderate bluish, pale-whitish, ivory-colored, dirty yellowish, and bright colors. Nodular, knotty, plaque-like, undulated, more or less raised and xanthoma-like infiltrations. Diffuse skin patches, pileation retained Shortened and watch-glass-1 ike nails Swelling of hands or fingers and/or forearm Extension of changes to forearm or upper arm region Drumstick fingers Impairment of skin's ability to slide over the supporting tissues Tight edematous waxy sclerotic consistency of integument Also: Bloated mask-like facial features Flattish indurations in the cheek region R&S 109537 -7t In studying the contamination of the air in the vicinity of fi` t-1.ypc driers, when d ry ins; po 1 ych 1 orov i ny l resin, vinyl chloride war. not f'.....i! m 82.3"* of the samples. In the remaining samples its content varied from 0.7 to 0.12 my/1, while the air samples in v;hich vinyl chloride was found were collected in the vicinity of the fresh resin, in areas not equipped with local exhaust fans. In areas where driers using the V. I. Stroganov system arc in operation, there is a significant contamination of the air by dust from the finished product. The dust escapes when the examination doors of tide furnace are opened (in case the technological process is disturbed), during the crushing and sifting of the resin. The dust concentrations of polycholorovinyl resin at the oven varied from 20 to 567 mg/m^, while the crushing and sifting processes as well as the bagging, produced from 25.5 to. 62,5 mg/irr. In some cases, the vicinity of shaft-type driers was found to .have a high air temperature (23-37.5 with an outside temperature of 11.5-23.5). In order to improve the sanitary working conditions for those engaged in the operation of shaft-type driers, it is necessary to equip all areas with raw materials to be dried with a local mechanical exhuast fan. It must also be provided in places where the finished product is likely to produce dust that could enter the air. Drum-type driers are used for drying coarse, fine, granular and finable materials; brown and anthracite coal, sand, clay, phosphorites, grain, granulated sugar, sawdust and the like. In the operation which we examined, the drum-type drier was used for drying crystalline salts of the sulfates of ammonium and sodium. A drum-type drier (Figure S) consists of a rotating drum, 2 m in diameter and 10 m long, connected at one end with a furnace and at the other end with a loading bunker for the dry product as well as a gas pipe for trapping the furnace gases which have been exhausted. There are metal shelves inside the drum. The drum is rotated by an electric motor, acting through a gearbox. The ammonium and sodium, sulfate salts to be dried are fed into the drier by a screw conveyor. Drying is carried out using furnace gases at temperatures up to 220. The dried salt is transported by a screw conveyor and an elevator to the bunker for storing the finished product. The operation of the apparatus consists of monitoring the instruments and adjusting the salt drying process. In the course of drying salts in a drum-type drier, the air is not con taminated by toxic substances because a vacuum is produced in the drier. Meteorological conditions in production areas near driers arc unfavor able. In winter the air temperature was 1S~32 and in summer from 21-35. The highest temperatures were recorded at the window of a drum-type furnace through which the operator checks the feed of salts into the drier. An air shower should be provided at this point. - -7- IV TVWk R&S 109538 R&s 109539 TABLE 4. SPECTRUM OF MICROMORPIIOLGG I CAL SKIN CHANGES Flattening of rete function Interstitial edema, deposition of metachromatic, fine-granular, and filamentary materials Plate-like fibrosis of the coriura near the epidermis, thickoning of collagen fibers and edematous relaxation of the collagen fiber bundle Fragmentation or circumscribed clumping of the tunic clastica Thickening of dermal arteries, hypertrophy of the tunica media, fibrosis of the intima, endarteriitis or endarteriolitis Dilation of lymph capillaries Inflammatory and predominantly lymphocytic pervascular proliferation with few histiocytes, involvement of mast cells Degeneration of finest nerve fibers____________________________ TABLE 5. SPECTRUM OF X-RAY CHANGES (Almost exclusively, phalanges of the hand -- often excluding ringed fingers) Cortical changes Circumscribed rarification Crescent-shaped defects Periarticular erosion of interphalangeal joints Striated translucence to the extent of osteolysis of the pseudo-fracture type Central osteolysis Shortening and/or swelling of the ends of the phalanges Acroosteolysis Circumscribed (reparative) structural thickening Also: Osteolysis of ulna, radius, clavicle, patella Widening of iliosacral foramina Our data and deductions on the etiology of the syndrome arc extremely scanty. PVC was synthesized by Regnault in 1S35 (see [12]), and large-scale manufacture began in 1927 [10] and the first publication reporting damage caused by handling PVC appeared in Romania in 1965 [15]. In 1957, the German literature still contained no mention to danger to the health in discussion of the syndrome [10]. Other patterns of damage are mentioned [2] especially the acutely toxic ones [4], W'eichardt [15] found in 1970 that, despite the fact that Germany produces no less PVC than other countries, no disease attributable to it has been found; in 1972 Juehe and Vcltman [7] and Juehe and Lange [6] published their observations on the topic. From the relevant publications [1, 3, 8, 10, 15, 16] it can be deduced that only long-term close skin contact with incomplete VC polymers or various nedium-to-high molecular intermediates (resins) and/or their aggressive additives such as plasticizers, stabilizers, accelerators, inhibitors, etc., lend to chronic toxicity. The characteristic pattern of damage is thus far known only in workers in the PVC mnnu far: u r i ng industry who have to scrape of: the residue, whoso exact composition is unknown, from autoclave walls- -8- (polyclcancr [16]). On the other hand, diseases of the kind described here never appeared in those working with completely depolyneri: ed inert, and physiologically harmless plastics [16]. It is found from the literature that the pattern of damage is to be interpreted as the result of factors which may be chemical, mechanical (con tinuous scratching and scraping with polycleaners) or individual (only 3.0 to 4.5*; of people doing the same kind of work are involved [1, 16]). On the basis of the job history of our patient, who for years had to spread liquid PVC in his work as a telephone installer, no decisive pathogenic roles can obviously be ascribed to the "mechanical" factor described above. For the "individual" factor it should be noted that it is probably to be seen as individual contact of various intensities with the responsible agent. The degree of strictness with which the individual observes or supervises the work instructions can also explain the varying frequency with which the syndrome is to be observed, and the differing periods (months to years) before the symptoms became patent. The job history of our patient instructively supports this interpretation of the "individual" factor: he was injured earlier and more extensively because of his special job causing his extremities to be coated v/ith the film-like "special" polymer. The mechanism by which the "chemical" industrial toxicological factor comes into play can in the first instance only be sketched: the subjective symptoms and functional changes -- supported by macromorphological and micromorphological findings --point to a (initial?) neurovascular disturbance. More details will be given on the etiology and pathogenesis of the syndrome in a Iter publication [13]. For prognosis and therapy of the disease after discontinuance of harmful contact while on the job, wc may say that the skin changes revoer spontaneously [6, S] and the latter can be promoted whenever possible by physical therapy, as observed in our patient. However the bone lesions can progress even after work is suspended, finally terminating and recovering. Summary Case histories of chronic intoxication caused by intensive, long-lasting skin contact with incomplete vinyl chloride t'olymericat ion products and resins and/or their additives arc presented. Paresthesia, functional, and macro,mor phological and micromorphologionl changes build up to a variegated pattern of symptoms. A syndrome of sc 1erederma-1 ike dermatosis, Raynaud's and dead finger syndromes and pat hognomon ic hone defects arc charnct erist ic . Ifhcn these symptoms are taken together with the occupational circumstances, this easily nisinterpretable disease can be diagnosed. R&S 109540 * Tg.-M.-v -0- R&S 109541 bibliography Ch'th vjn, A.. 'h Nt'/'si 17n S'n* th.mto tl'Acf^'C'1 .''.'"''v',,.' si'O'^-'-iv: iV.^uw <t uV C "fi: ic.i(cn ,''*v;/ w .*/ <;*> I J. vljJ.t/ L'.ttfoi. -S, 2##--2*0 O 2^. Gut?. S" : Vcr ^ rvi A.-Sou-i nil Kw"'Ufo:in. V, u;,, McJ, Vsuif. i U`, *.>3 -- <S? (1966), X )N*rii, D. K.f V W\ G. T. Ai)\v*v: Aero* ftfrolvtiv (\c. ; In Ntn Ifs.ivjyd tr* tho piitvov'/;; \m'\'.-\ o? Vifiv! ____I'ru,. MoLi-_J - \ * vy*7} f ill, 7*3 -- 7 I {. 4. > U ,s\; lit. f*. 13.. A i'.ioii* A: J i C. rlcmf: * * l*v>! J f.Cwf Hi t Crint.\!i." JuTi nSi ^;!r*f n'r :?r> A:f(' linen .** ni Urn Vmj ;d *Ct>p ', * rr-.jrv n. A rci. Tn\i*ml. 2V 62 -- 73 (PA'CV* 5. Jahonh*, S.: ('w'x'Jo^Icfr.Jwfmt'vfv. .WJ. Klin. 62, I 13;--- i (1962). M; l*>* t \* K, 1 l.; (, .'I. iTiiiviutii K`r M I.. \ t If**' p itUt, a il.v imiii no I \ii\,nnl,il* n. llinl* Jt/t (i".'u, 12\I , U*\n*i*, 11 ; t I*. <'* u. At.Hi.v. S. S3S 3 ,* Z m*. t i.m*\ <t * Ii.uuf'tin,:: Si mu ,;r (* l 'Ai6. 13, SrtNr*nv\. V. ,M/m,hi; %* Sf, \\i k\ti \<i f: /if Am*-/ uio^t .toi* tU*% 3viu(rftiM n ! \ tt. *<*( umi nut f i J IV'v nv r i' ih n i.t-J ilv*r Jvfv ii jU'Ikn ^lo Wrivroitun,;). 6. 1'jnr, 5, 2; C.*V. t ''-cr: V-I.vr^Vr-nlc- ;c /1 .it#: ;*/. >. n.;jj *s*. n- !ro-t ;i**J AUfi,`N- '**.*# l*i Afr-*s**rn tier I* V*C Kcr wlA-uS. n J f .iuvtf ;i?. i):v.h, McJ. VAJ.r. 9/, r*;2-i'/2i (! 7* Jt;ir. S-* G. Vi 'A/ r.;ns Vm v[%S!ofKl-Kr ir.^I ;tf. [ !:i:v n.llvt Synipotion 1,1. f V* i`f'.\jf/;c Ov*f Cic* (im!,V' 2/. <. l'A'2, S. Musoi ;r^ ij. S* I'*'- i. W** **c M. S. K: i/'.-x: Ac/ootU'ul^ ut. D.-rm. lC6t 2*9 -- 223 9. \U\u4on, L. 2c G* C, N!nfn; Cu:j- nn.is l.cttom in Av t**;v'oA *.i. Afh. l);nii. {Cm.-a;o)( t:*., 22-i--22? (19?;). 10. Ocrtrc. H.: Gw`\..nj;icis^;.`i jSfJur. * du:\ii K`jnHiCL>nV? 2; tp>. l*h.fi. 232, 77--132 (P ?7). H.`* M . 1.. i. i- i n*'. ** *. ! Vai i s*. m: ( Mttl ( l! III,. i< Hi . It i |l II i * H * 1 it ;#** *lu*0 it J ..(.I, if,- v Hill. IllCiflt. 1 1 * u*-1 !. ' t/K (J'K-3;. IS. V%`| It M ,ik :,r, 1 I.: 13tw- I I inf; til il.r K nimMi.f 1 m i!w\(mc. i*ortii! \ ilcr )i i-\ 11 * 'n IS. 23 -- 34 (1V 7 C)- If.. W*ii\.s'# It. M.. \V. I'., Ml c* m\iir t,, I**. 'I'a ft'M M J. I. , {^Kdi; ( tj; M i*in il I- Amor, jlvil. A\. 20* >77--SSI (1V67). \ \