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tic phosphokinase oJrich as opposed abnormal battery. :mal in 3 wi cks. : !ic results of these it SMA-12, battery, is certain that the >t in the liver. It is special procedures tne liver, indicating ..rcoma of the liver that the battery of normal SMA-12 . ,t abnormalities or rs of the employee :ocol will change as tier method for de'.*! vessel thrombosis chemical plant is upounds and resins, tilts were reviewed, .'ina and 11 cases of eloped in employees liver in the nianufacl. p.mangiography in the ..` ol. Clin. N. Am. 8; cons cholangiography. msjngubr approach to J. Med. 2*9: 227-231. .n of spleen size during .era. J. Nucl. Med. H* UNUSUAL SPLENOMEG.AL1C L.IVF.R DISEASE AS evidenced by peritoneoscopy and guided LIVER BIOPSY AMONG POLYVINYL CHLORIDE PRODUCTION WORKERS H. J. Marstcllcr and W. K. Lclbach Medizinischc Ur.ivcrsitutskiinii. D-S3 Bunn, Federal Republic uj Gcrntjny R. Muller and P. Gcdigk Pathologischcs lnstitut dee l:nicersitii: Bonn D S3 Bonn, Feilcr.il Fcpueiii of (jrrr: uiy lNTitOIH'1'IION Economic Considerations, Technology As early as 1833'" and 1S3S," respectively, RcgnaiiM in France succeeded in preparing vinyl chloride (VC) and polyvinyl chloride (PVCi. However, the road to large-scale production was not opened until vinyl chloride coulJ he synthesized from acetylene and hydrogen chloride (Klatte and Zacharias. 1912)' " and or ganic peroxides were used for catalyzing VC polymerization (Klatte and Rolled, 19I4).*1 In 1928. PVC production was started in the United States and in I93J in Germany." The enormous growth of VC anil I'VC production capacities over ihs past 45 years ran parallel to the rising economic importance of plastic materials" (Taiu.i: 1). PVC-producing industries in West Germany increased their production, parallel to the development in the United States (Ta,u l 2l. at a rate of 10-20 percent per year from 1960 (172,673 tons of PVC) to 1972 (930,701 tons of pVC and poiyvinylidenc chloride).''" Total sales of PVC amounted to 850.140 German marks in J 972."' This enormous increase in production capacity, espe cially in flexible PVC (U.S.. 1965: flexible PVC, 90 percent: rigid PVC, 10 per cent)* can be explained by the almost unlimited use that can he made of PVC Diversification of PVC markets exceeds-ih.il of any other large-volume thermo plastic and is one of the reasons for the increasingly favorable market situation (Tasi-e 3).`" Rigid PVC is-used for tubing and linings (including insulation material and drainage pipes), foils, films, and sheeting (packaging, lining, recording tapes), profiles (blinds, window frames), tiles, sounj records, and fibers. Flexible PVC jj used for cables, foils fdceoration. roof covering), profiles, tubing, artificial feather, flooring, foam rubber, paint, varnish (lacquer). and toys."' Thus, indus tries that manufacture the end product operate on a much larger scale than those producing the polymer, but the companies arc often identical.'*'11 Technologically, vinyl chloride was synthesized mainly by hydrochlorination of acetylene, a process which was almost exclusively in operation up to 1960. fcal in the Uniled States now accounts for only 7 percent of the production." Vinyl chloride can also be prnlueed by oxychlorination of ethylene to 1,2-di- chlorocthane which is then cracked to VC anil HCI by subsequent pyrolysis (now 93 percent of total production in the United States in 1972).' UnJcr 95 m 9 SPl-03078 6ioeo-idS JZ c . . ^ *- ~ J -1 3 " s' $ s .1 = -5 5 'i ? i - V S-=-S"g= c3-j^'c i ; 5 Jd a= a;-> :<*^ 53 i--=d. -a c-^ "l- = s-c 5 sr S*. !=j --3 ._ "'- > i : " -a > " X -- v"0 > = = ==;- = > I41| 1114 - >. s s 5 *i *> sf Jr cu i_7r *, 5= es..y- >** ?-- ^ --i 7 '>. '-c = -2 v 3 i - -1 5 2 s =I- " 11 s I -i -i i ^ 3 I u #2-7i ^.2 2 i 2E. = ~ - r, x 5 = - u '3ca - - 2 > Sorc-s~^iS^ t5't^;u_r1i*. fS'HiS-56 25 -5 - 2. a g t ; 5 e = 2 = - % ? g u ? 3 S .at^s .j>2 " 5 V w J- -5 ji 5 i__, i tCu J5S 8 r5 sWi e-S 8.2 3S ! g.gf 5 "s* tT. 2 O-J3 Si ei i- , 3s > y- o-<o V^ *3 ,, 22 r= .>- o 'Ss >* S* Q 2o 2 CU I oi c <c SSSS > c 3* VO Ov *t v*iPMO\or ~ -- Ooo *""< v> o O -- rt w : I c'le-5'C--Nrv.--n- cdod-d- NO--CON :Jiif- GO od 3 t> - iuO 2 U3 3 V u C O k- -- 5 *.= ~ wca2fS JiS^uOl- il.!! ii } 2. I #TNCO'0'0'nTnfH-ifl ;} it i--------- - It . I! I: 2f i; I M1 -3 Ic- iJO^ 5O. 2Wl l! ->? i II s ^ I ill II s -3 >3 u *C *H Cf iCJ Vy ' | .= cLuO* li=I = i^ : *w f "C h* i o HEoo 2 o *,*-- 2 v" Cy "c k ^y --.** J"53 wu-c3 nG q3 23 <25 '?U S o j: a c. 0 UJ > Ou, 00 i.i.U OuJ -- " J -a " c. o ?, > ilT5is-2|c3 D? 2 sS'SZ < 3 o- 3- Z^>n'zcH^'S 0 ?T .,,>, 5 >.. * : 21 c c *?15 = -3 "72 ^ ~3 z--'ISo^ssJ^ as.a-jfegSuS ji>1 o = - "*. -s- = =- 5-o >w o o y '. .$ 1./-3= - - 25 2% ES-w6 S s.r-o s; S ss O^Og^OO ocw2j*j2*jwf! -^Q>ju= E y sW- ,CS,J . T*-r^ w 2-' I E S 5 >;2 3 -a * Ss 11,3 00 s = i .S .2 S -5 > 4 - 080C0*ldS ** * Annals New York Academy of S r.c-i: Table 4 Clinical Manifestations and Fatalities among Workers in Vinyl Chloride Polymerization (PM> and Polyvinyl Chloride Processing (l'C) (Review of Literature) Autbor No. of Workers PM Pi" Actwtco* Skin T"* Phjo^-K.o ,n"n` Liver mlrbK Acute Intosiration (KauWtioj 8 Dublin and Vane (1933, 1941) Tribukh et al. (1949) Chief Inspector of Factories (1953) Harris (1953) Devigneviclle and Flucher (1953) Parmeggiani and Sassi (1955) Filatova / al. (1957, 1958) llervieux and Tessicr (1959) Danziger (1960) -Suciu el al. (1963, 1967) Filatova cl al. (1965) fusion 11965) C'urdier et til. (I9ft6; Chstelain and Motillon (1967) Marin et at. (1967) Spain Italy I M'III III ,1 ./ I I '#* / I ............................. A.I..............I N .t*I. u * t I m. < , M. 4 Mill I J-//UI I I ( IV ft Hlltl AlHOMVtl/llt'flko H'J/I / I iiiiiuan ri a! <!*>/! i Kramer and Mutchlcr (1972) l.efivre (1972) Markowitz rt til. (1972) Dugois rt al. (1972) Misgcld et al. (1973) 2 73 -t 13 145 3 168 163 3505 123 441 528 1 I H I !l It,i, |ti 1 .1,7 VI 98 780 2 I 178 i .<"iti l 1,257 1 21 -*(?) -*(?) _10 10 22 Sit 15%* 5 12 5 12 1 1 5 II 7/ 5 II ii M ) IF I "I lilimic lit i iiltstlminl imlsimiug" II 2.1 I Slight** 19 I2 2 1I I 11 1 Slight intoxication Collapse Second-degree burn 1 Slight narcosis, 2 fatalities Total 10,056 2,582 86 F x 12.724 HR 97 40 73 5 Acute intoxications 3 Fatalities number of abnormal findings not slated. 1 --, number of workers not stated. J l.iver biopsy in 2 cases--diagnosis "chronic hepatitis;" splenomegaly in 10 cases. 3 350 workers employed in the Swi rdlovsk plastics factory, number of I'VC workers contained therein not stated. * Liver disturbances in 6.57 percent (23/350) of 350 chemical plant workers, in 15 percent of I'VC wtorkers. |; Palpable liver and persistently raised serum bilirubin. ** "Some changes in liver function." with statistically significant correlation of BSP retention and exposure. M arstcller et al.: Splenomcgalic Liver Disease SPJ-03081 O Annals New Y o rk Academy of Sciences No> Table 5 Vinyl Chloride Exposure in Laboratory Animals--Acute Toxicity (Review of- Literature) Author Specie** Ctmcrttlrs'ion tp|<n) Length o! Effect Patty t'/ a!. (1930) Schaumann (1934) Schaumann (1935) Peoples and Leake (1933) Ostcr et al. (1947) Carr r; at. (1949) gt 200,000-400,000 "Very short time'' 100,000 5,000 30-60 min Several h Starling heartlung prepara tion (cai)t m + r| dt mt 230,000-300,000 ? Slight nar 4 h/5-S d: I h/ cosis J 4 v, k 100,000 3 h/7 d during 3 wk 245,000 285,000 10 min 85,000-125,000 10 min d + rbt 170,000 ? d (61 d (7) 100,000 (narcosis) > (narcosis) Fatal (lethal range) "Dangerous to life*' No severe acute dis turbances No cardiac failure Narcosis Narcosis Fatal (lethal range) Minimal anesthetic range Narcosis Serious cardiac arrhy litmias Narcosis: sensitiration of myocardium Lung: edema Liver; hyperemia Kidney: hyperemia Liver and kidney: no changes Liver and kidney: no con siderable changes No apparent untoward effects even after pro longed anesthetization1- KfAstromattco tt at. (I960) Lester e: al. (1963) m (5) r (5) g (5) m (5) r (5) g (5) nt (5) r (5) g (5) g (5) 100,000 2TO,000 300,000 400,000 ft r (2) 50.000 70.000 100,000 150.000 30 min .V) min 30 min 30 min Deep ( narcosis--side position with tremors Deep narcosis (I mouse dead) Dead; g in deep narco sis, 1 died hours alter exposure Deep narcosis, 1 died during, I after ex posure Moderate intoxiention Righting rellex lost Corneal reflex disap peared Deep narcosis, I rat died of respiratory failure Fatai outcome: Lung: vascular engorge ment with hemorrhages and edema Liver: congestion, partly fatty infiltration (g) Kidney, congestion Clotting defect Survivors: "Little diircrencc from control animals (liver, kidney, spleen, brain, heart, adrenals, lymph nodes, eyes) except for pulmonary congestion" "No visible gross pathol ogy" Lung; congestion,'edema Abbreviations used: r, rats; g, guinea pigs; rb, rabbits; d, dogs; m, mice. Number of animals stated is given in parentheses. Number of animals not stated. 1 M arstcllcr er al.: Splcnomcgalic Liver Disease SPI-03082 Uoi Annals New Y ork Academy o f Sciences Tabu 6 VrsvL Ciilorio'e Exposure in Laboratory Ammals-Chronio Toxicity (Review ok Literature) Au'brsf Sirrctei* Coaccatr^tiofl Lrnfth of Exposure Kr*(*ms pAtholocy Torkclson et al. (1961) Lester et ol. (1963) r (20) r (2d) 6 (9) rb (3) d (!) 500 7 h/d, 5 d/wk for 4.5 mo 200 7 h/d, 138-144 times in 204 d r (5) 200 4 h/d r (5) 2 h/d for 6 mo r (5) 1 and 0.5 h/d for r (5) 6 mo 100 (same procedure as in 200 ppm) r (4S) g (N) rb (6) d (2) r (IK) 50 100,000 80,000 7 h/d, 130 limes in 189 d 8 h/d for 2 d 8 h/d for 13 d r (10) 50.00 8 h/d for 19 d Normal growth Normal in appearance, mortality, and growth Normal in appearance. mortality, and growth ``Entirely normal" Normal in appearance, mortality, and growth Normal in appearance, mortality, and growth Narcosis, 10 rats died, initial loss of weight, followed by normal growth ("tolerance to the gas") Initial loss of weight. followed by normal growth ("tolerance to the gas") Liver: average weight increase, centrolobular granular degeneration Kidney: interstitial and tubular changes Liver: microscopically normal in rats, guinea p:gs, and dugs; centrolobular granular degeneration in rabbits (together with necrosis and some foamy vacuolation in male and necrosis with periportal cellular infiltration in female); weight increase of rat livers Liver: average weight increase Liver: slight increase of average weight in rats after exposure 7 h/d, 138-144 limes in 204 d and either 4 or 2 h/d for 6 mo Normal Lung: acute focal necrotizing pneumonia, edema, metaplasia Liver: parasitic cysts, moderate to marked swelling of cells, definite fine to medium or large irregular vacuoles, compression of sinusoids Spleen: lymphocytic hyperplasia in cluding most of the inters'.itium Liver: parasitic cysts, marked swelling of cells, large irregular vacuoles or clear spaces, compression of sinusoids, changes focal to diffuse Viola (1970) r (.'0) r (25) M.om 30,000 8 h d. 5 J aak for 3 mo 1 h 'J, 5 d/wk for 12 mo Norma! in appearance Slightly soporific, normal in appearance and growth After 10 mo loss of weight 13 died from carjiorespiratory complications, 2 from hematoperi toncum Spleen, kidney: no differences be tween control und experimental animals Liver: parasitic cysts, moderate to marked swelling of cells, definite fine to medium or large irregular vacuoles, compression of sinusoids Spleen: no differences between con trol and experimental animals Conclusions: 1. The only finding suggesting a specific toxic action of VC is the increase in liver weight on exposure to 50,000 ppm for 19 d and to 20.000 ppm over 92 d 2. Morphological alterations with out pathologic signilicance Liver: increased volume, smooth sur face, sometimes subictcric, some what more brittle consistency than normal Microscopically: Alteration 0/ Itepatocytes with marked cytoplasmic and nuclear polymorphism (torpid degenera tion of the cytoplasm to necrosis) Proliferation Intel hypertrophy of Knpffer-eelts Pound cell infiltration of portal I rncts lllfykutle of portal eapillaries, cent rtdnltular veins anti vtnnxnids by numerous centrally located areas of partial necrosis Intensive fihrnsrlcrotie reaction along areas of degenerative proc esses rany ehttnye Kidney: signs of tuhuloncphros'S sometimes accompanied by chronic interstitial nephritis j M arsicllcr ct at.-. Splcnomcgalic Liver Disease SP/-03083 AuiHcr Viola el of. (1971) Basalaev ei at. (1972) Table 6-- Continued CR"^mVLft;:h of Efpoiure Kn^eav r (26) r + rbf JO,000 4 h/d. S d/wk for 12 mo 11.7-15.6 ? Slightly soporific, nor mal tn appearance and growth After 10 mo development of paraauricular tu mors PatboJocy OO*. Arteries: signs of endothelial fibrosis (with thickening and dissociation of the elastic membrane), often with partial hyaline degeneration and homogenization of the walls and proliferation of endothelium Skin: superficial hyperkeratosis, thickening of epidermis, dissocia tion of collagen bundles, diminu tion and fragmentation of clastic reticulum Bones- extensive periosteal prolifera tion of cartilage-like material (small metatarsal bones) Brain: degenerative lesions of grey and while matter Nerves: surrounded and invaded by - fibrotic processes Liver: enlarged, very fragile, "severe chronic hepatitis" Kidney: swelling of parenchyma, often tubulonephrosis Lung: interstitial pneumonia Brain: degenerative lesions Tumors: skin in 17 cases; lung in 7; bone in 5 Cardiovascular disorders Changes in bioelectric activity of hypothalamus Hyperadrcnalinemia Osteoporosis and resorption of bone tissue > 2 3U. VI 2o S >or-<r > oCOpL o * Abbreviations used; r rats; g* guinea pigs; rb, rabbits; d dogs; m, mice. Number of animals stated is given in parentheses. \ Number of animals not stated. o Si w ---- , o 5CE 0m 1n ~ Id cA 5--* rr s1 5' \C Id TT Id Id < - N> mnn TTTTIo I jen In- A Bt . r* _ i. 3 *< n v 3 . rE = t 1 CL _ ft ( 3 H. S5 A . . --. < q! Zo o< 8 = * 2" 5rt O* ?cr ! Pr-i < i o ft ' I O 7' ro q 1 99 ( r*< ST. ' oc C ;3r,*i_f 2 |c| 2 5`T S Tp \ CL 3 2". A< o1' I'* * fs 35 o-A w. "A<5 Cg Is* 5 a 0._--. -- la I Icrll li= 3 a ft .. s,,. u ^ Z. 3 g s n EJ ip yfi^. . =HII l = srs?2?sS- s? ** 95 / a* *2.3 * ^ ** Hsir'-flfn at n c_ .^2r5. nr> eg So351115 Sgo-g? = s^: ?H o-Os =2n. 3P 9p5 O Jjn 5. 5- 5T-S Si5 C &IA ?i; 95. ~ 5 ^ av o* c Oz. = n ' cr. a- a* p. ^ 1 o K r; o3 < ft *1U Po d^ -wa J ;11 !1?; a?f f'g s a5. .-3 * 2*.* 1I O3 ?rf.- y ft C c <- n a r. P = 3 o 2 a ; s' II Q-- 3 n0 = ?t- o ?p =r *0 2 f " r. <2 0n C. --v ^ u m C *" c-S"w* c ^ ^55 < n"n = TJ S B ft sll t. 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O 3 r o<-) ' D SPI-03084 S800MdS Synopsis of A n a m n ls tic , C l in ic a l , B io c h e m ic a l, c o r'c > a ND* H is to lo g ic D ata of 30 I VC W orkers' " Abbreviations used are: N ationality: Gcr, German; G r, Greek; T u rk , Turk A* Palc*'M *0 broader concave posinecrolic scars; PC, patchy perihepatitis Job Classification: PM, VC polym erisation; PC, processing o i the polym er; />,, ,;inea," A, augmented; U, increased; H istology: ( + ) , m inim al; + , slight; neoscopy: U , slightly irregular or undulated: G, granular to finely nodular- j, moderate; + + + , marked, coarsely nodular; C, comma-like or stellate; K, finely to coarsely reticular; s' u j 4- 4-4- + 4- ++ + + ++ 4-4-4* +- + 4* 44 r 4-4*4-4-4- 4-4- 4-4*4- + 4*4- 4*4* 4*4 t 4-4* v*in \ its*qJc*u | 4-4- + +4* 4-4- 4+ 4 b f-4- 4+4- 4-4-4* 4* 4- 1-44- -4 4-4* 4*4-44-4-4- 4- 4- f- (IBM ,<q 9TIS >V -na C* A t -- -- Cri r*r*pa.i 9*> * ---- *" m9, -- ***' * ~ mm"' B PI C> ------------ C = -- -- f t O * m m "* " m m * "* m Oo m j~~>=; g %--~;2v:*r. *12>r*.*----*"S3.--c--^-O-- g % ?------ --*---"-"----*S*0 " Z 17. 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"O3 wc 5o 3-g -- o/, ^a Uu c n *J r,! *C o -i v 2 o s o . u<y tuS ^ 3 C^ -3 -- .* c o .> .r2r 3 cr c -3 " O = i-s J *7: n - .5 "x g 12 o < o -c * C T3 .Si o c je 5 jS i V ^ 2 j i > > -O O. e .p5 c 5 S C -E. c 3c -^o ^. s; > *c i 2 S 4 *S 9-g.i 1= nU I.S s. 8 E fg. <5 *5r 2 f.E-Si o m a" ,c 04 Cy Si e g c S-E 3 1-- o .8 ' i 5 - 5 3 21 ilH -- *- C 2 "c 3 ! % ^ s fc, ii>-C 'J -- i: 1 c u j; u s u .s ww ^J Hi! o 4> e s -= = ^ CC co *^ S---*. cc O * S'. 5*3 .cS -X ~ il * s*: < T? J f = g 5 8 o a. o fl J v> y c n !S 2 -S 8 - <J C <j I'!tu y2 ^c 2y M'3: <AJ s^ C C. - u? - 1 5 5- 5 *X Cc yu U! >;; CuO 7 it C .2 * O r c= --5 C. OO A ft -- 2^ 3E _c= Cc 7n oo 3to >v oc ! =0 il T3 3 y <a u w*2 .. c C3 - y g'S^ -svu -- - Ej f ; = y S2= u X V = 5^ A R 2 -s l y * o o Z c c < H j 2S C x il o :i . -cA nc--o>s> CC oB :-Ij o 2 5 u 5 *- .r 2 j*! u. 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"mux ~ n E ,u O -- ^ o c =5 g ^5 5^5 s ' O so ^ -. <Lri := l!3 e a2=r XA< X Ws= = -J c -- -- O ft ^ *.' 5 =-- c S 3 \a > - V a " x **Py 75i CaTT*`` co E 2J >s X X w < S .2 S' 5 ox^ C r*-5< -c2- 'w X c a 'X 880C0-ldS M arstcllcr ct al.\ Splenomcgalic Liver Disease I Annuls New Y ork Academy of Sciences o-?1 *t U> :5f a1: 3r ; i< H z- >. 5^3 s !i ! 0.T3 So 5II S- !it' =3 u !j '# lsi 3r .c5x I ";lI u m ccs ||I ecu~ , C *j U O* O eo '*S tt M *18u S9Sg` "R M .. 3| 8-o Joc '--o_eo "ri a. -- W v> M* *T " 3 r- ll . a Hi g?i " " o JuZ I <=i(J 0T4 Eo u SC'c; .= u U !> 5*0 > > : Gw---- r eft o c.oX>s->oN XA CtoXoM vM 8 = 25 s --w u u -- c Sr = -i- U ".c.c * "3 X-------- -=2 O I J/ttK 5*-v xa"t ** JE -- 2 JS- c w 3o .1 I--O sau .S5 gu eu- J*y<" u> 8 _ 23 S3 2 S- 2S 5g .O 3> --V ** J^W 5 Z' j c --y O3 7 . >o X TT c >* O 3 <*> X G. o "3> ii O 'X n y o " '3 . J5 c 2 -o " o x ooy= S " D. ,, > 2 0 ro rt '5 a= S S-S >? X <o* x>o* s-- SQ. -c c *o3 X 8-cgS . crt x *. a s >. |s? 5 u 2To cC U= "3 jj as 5> 8 > rt " -3 E 0 ` fj 5 all .2 .2S Eo S3 S'sS < C x 3VU eteo C .3 8I :jb a oe ?'r C| 0 ,,S> "o (3 " a c s _ o. * 7. "= -S 2 8 STr* wO ^c .c5.8o o g jy t o u T3 ^ '2 E'/I* 5w 5&I& s*"53* . E-S-5 a.0 u Q 0 (J fl = S >> .-Si w-i --** rCC.:.-_--x--2"3 J `Efc *3 o 5* < 5? vw >y cc --W j*z> o o 2 o'C | c 8a -- *3 >C>. crt C l *3 *3 2 *5eooc j:a=- 5 i"s CCy " e ,, s a-o wO O8 S ko. -c3 W <M i-B o o 5.3 o if c - o oo ^ 'C S f*1 E* 8 >, .3 o8e " .--5 -C" rt0 g-tf ti O g .S c C ioso0 -*-- 2c si 2X 3o ->t ioi w. */> , fL u nrt 3 > *3 o u o es 3 oN o eo o O 'c 3 J2 c o X Hw *3? o .5 3 o 52 :5.i *-- iff iH ! 2E I-8 c --u 5 oo o *os s-s .Ete oo=' x5o o X a .8-8 eft 2e *3 o ~^ X^ol o <9 X ^ o '5 0-5Uu fs-sc-^" C0^0-.3'-= wx <n c ^ V S; ^ I 8. of OX * 3 i ^ i: Z 2? > o Ci.y^ UX & c e 3 ol II 5 i l ^w n0.2 e S? - O k. 5 /Oci o 3 *5 .-- --Ee O --.>2 w <5 a o. cwc.2 >.| U X Stl" 2 ox^ i5 = 8w C.-3o _3 SX s *OoZ yx>>-35'oU 25_OoN. ii c X 3 &c X *>o c o sOu aC5 J:, ft..G 5 z % 0*5 o> 5c er 5: U. I ^ . *3 ft. ft 1ft. 3 g c = h W- _5o-2^24 "oX,X"Co0O *^o35>0xo.=IoSorafak eft c oa* x --SO > -- X s- > " X-- >%o u. *3 C O .g?_.-Soo(1 ^X X I-S5 5S 5 o ^ XJ 0 . o C X ?3 X 7 a fl '' _ 0= ^ --X Ec U o 8. .e x u-- Cc X c eft^ --G H ft. - O) so Annals New Y o rk Academy o f Sciences | M arsicllcr ct at.: Splenomegalic Liver Disease 680C0'ldS `3 8 " oc o3 o5 sN S .-.o u tfsu 3Sg c-- > cm ^ o yg* si 3 8"SI b2f>i?C5 Sg, w - y_ S.S2 W J*3 ia. 3 3 r=6 iU. *V3 P> 3=1 vU> .5mQ^S ill o J ^ -a3 a sl ils ! j- i E :o o to ?j 1 .5 t- c Xy X ; .5 E S ? | i w ^ !x o o co >4> O C ; 1L 3 2 v3i X2 a. -- c O c f~ 3 5 -a 25 $9.5 15 - S * ss .5 U) >> = 2 - _ y. V ft oc a0 0b LJ 5 8| c *? 3^ 8 g 2 > S.S s ^4 0 V x SL-g O " 'o c >> X >s -7 3 y y "n % 8 c .y 2 c c cy.. C. C 5* O* MI* 15 13!S3O ^ a 3 '3 il W U O (9 > \i V) J?3 oI*rt X) 3 = g = w <^ 3 3 = ss " ^: 0w O U lr "si 3 S>f ^ias 5 .2 3 I^| ia. "> i. c >> 41 .JO (C ^ 11 o2 iu.. Ji .g ,Ofl c 3 3 28-.325 =3 2 f CL jkS1; J <5 -If o "T3 =* II E 38 sui " S "Ml S M5 u5tf .2 >....s ~ s' S= --= 1I-s3 S8 3r2ir-3us* ^'S22 J.^o2CC "uX_"w.C5A*sL S3S3~Os=3>=i-sl lE t u 3aa 8 5 = " is Sgst ,10 3? 3m. u^ 0.0C* ,3, -* uz s ^ 30 - ^ x o32O3.5"2cC3/0JOu.-r'-XSwC==SEM=t*."M;CSI-.:335f-,*832# 4S* 2-3.Ma^ Co o8 2 s _> > 6 ~ '522 N3 = s. > .2 8 O 3 u 52 CcO -=> .J is 53- .-3 U O3 > v> O 3 fll : CU*3 5 X = 3U a 2 g6 f]3 or i " |= &Ea^ c = 2=3o LcPu --f-9* yZ s^ Ou g 3 O .3a -U<-SJ ct> uc; Bu> <OJ 3 Ow Sx* ife C, tCJJ V. -- "2 ^ 5 -- ^!cs- -- 2ft. Xc ^o .' sl|8 5-^ = 5 ~ co c N 3 w * y " y^ u- d. > .2 Cl - c . c ? ^ -3 e yx 3 s s ,, 5 . < -s t: yt 0 2. i5 ? 1 z | C r EJ ? ^? c, cu x . . ? 2 5- J y v J- 5 5V 0600-|dS M arslcllcr ct al.: Splcnomcgalic L r Disease L60G0-|dS J >x oa 5> ~ kV. --c.x :Jr Z * S2i a a a , i. -- r c. ,2 o c c -3 C "3 ^ " : 3 *; : C O' e. - X * . ! y S S. T* to v- -- -- -- 5f s O^"3 c ilf!mi e I 2= 0 fe 8 cv = -~6 &c --V ? .S 5V*J- a^^U" sT7>WrTsi *`.vZS_ 5OC O - r ci- a ^ 'j -- ^ '.Z IT 0*213' t c .2 = -7 2 ti:* i/ J c *_ X - a = -- u a ok. X 13 /i 25 r e * * .. *. >3 o kIP- w 5 ~ O "3 i -- g ^ ys 3.: y s ; E >. T3 SA -- c ' ? _32 ~y`i --c _e -- w --r * 2 2 3 x<-* a 5 s .2 Cy S v * o * _'/=-n. t... > r^ Hc ' --5 -x.c-5 -- rr ,s -- x-- 2c || tt. C3 c a O 5 -j 'z-/ w .=3 V V V - Xx 5 - ? E !J3 C~ - '. *?5- o- ' <j r c k. 55.SC 5VEe-ar C-- U ^ ^ <s C8 o= > ^ s X * . .2.2 La " ?* xw c H- S5 ^ e-s = ? - C. !J x - X~t X ^ -c-r = .1311 :>,= ;= c _ ' .X Ji 3a 5 -2..** WT i.o a --~>u 2 c'T 5 uj iil v ^3 ^ _co^il-2 S-i iD** --.C?3'Su,/. :i5) *--"*05 t* -- *".x. .3 -'.--9 / 5| C w* Xc r/s! 4XCw -^? = Co e- ?> = u 2 rC ^ 1--^ 2 ?'- = 7 2 X J U 2 I sf.SU < "5 260C0-|dS , o* > a * Oni"* jo 1; 1 m~ O 3 ri - nv !;iS 1! e li * TUSTS * T. >>!i l ; - *< 2 S-:! s <ii 0 m ;i t ;i Z to 1 V. cgu ZOS II SV S` ?N. I-- -- i:2 = / wC i: -j 0 .1 c. u ': "3 i'-ES Ill I ill ;<= 5 'i!U , . -C iif? VV o C^? it o --5 S=55 1!*;2c o* C~ afca --VJ \ ii ! wX <> -: -r /. ^1 J : x: 1 -3 I /? <1 _ I __ i V, o ; l R v i |ii 111 5< C- --: i*--2r- . = -> 5 :! = : ? > i -- ::is *:; y* c5A . "? \ * 0 o c* M .1 5;i >`\ co ; *1 "* co ?s;! 7.i. ' O ! * * * * " ., 1 .0 <*-v b>v v* / . ,>-,, *;V . ;-lP c. 3> Si d . V/tP.' <- .* i*5?r-Tk'i- iVv^f-: il 3 . " >. 111 I ! :i *N CN I 3.x! v F'- J: *,*4' V*/0> * ''.pV-'-^V - . XiCn *?>....} . *. :> ' * '" -/<, r-v:qO / '*' o ?_ E- I ?lsl= !i V- t. .>--?- V V. # ..'5v ^T O' ;* r * I 3 l| >5 I jr il 'OrsrOysC ft.o M fN >s z1 03 > Ov u1 2 J1 *-J oH Mu. :0 ho O >* 2< O-J 55 o Z ii 1 *5 < :o g S-i ? Jo 3- 2y W- u ri o 4: 2 >* 3 |i I Ji a c< 1JJ =51-3 "jto~n ;B^>-05 " jj - USgiJ ?2=j-;i23"57S if-111 * .a ^ O *9 3=ll?;=SSs -c3=^^4C"=c0=-t32== ivjCO"|2ft.Uu-y) 5c jSs>> tzc7, " c 5 s1zk3 IN = 'jCig-< =OC ui|< = U 04 'n O u i * *c ^ 11 P M s*:=l a 3 e 5o _". tA S .2 22o It-0 2^ ^ 3 2 w gS = 32 'S ^ 0 cc ca 1111 o o u> 2 n C ti . o j= c O u -o > *S m C c cfi 3 C 0S =o ^32 : c.a. o .S05 See 8.2|2 vi* e * -a 2- s -3 2 a oV oV Q, & y xw _-gc oc * s u v^n J>3N -- 3 u) .2 1 be .. U C \A * ^ >* Cu O W U ,__ ^ "3 2 2 o J? 2 ^ tU u 's 2 o -- = t: o 2^ s rt 3 k. 8 3 u y go 5S S^ sO o 3 vsl h; 3-a fi 8 eM5 ii >* toT; '' M03 OC= V0C 5.5 ^ .M i3o Mb Uy M V !0a 33 S 3 n <J c O M. X X-- . o 6i =x *-- oS js-S c i55 X3 3 * i 1.15 ~ C *3 g o *3 i ? 3 C ^ e *3 = -- '5 s -- v. a ^ h* i ^He*M 3vt MO 3: *=^.5e o 2 r- o cc o *= t ^ - O oe w . W s-.s 8 2 3O I "i ra .: = * *? 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ID tt* f3c' a3 o*3C" l3l--fo_ --* s 5. a-g x c. > 1^- s 2 0--n T*s\ 3 3 fCct'--'2^3 o _ a* foyt* =2 ~_"__ a ;ijs 2.< UlrUli * 0 c 2. 2 k 2: z= IS Zl t S 2.1 c g 5 n 5' 5 g- " aS' 3icD g2" O'^3 J lis s-5 = o r- s o *- 3 2 3 -< t -3 '-. O333 -- ,^"wo 2. =r 2 > : < H 3-< C 3 r* tO o**9 -? O - ^ o 5 O* o2 wO V$ js *r *2 *=_ * 2 O'* ^coCL?S-?-3 s 5! 2.:, !-2 j 3 S ^v ~^ I--E 3- 3~ ^ 3 5 O j 0 ^ i fr*32< c o-S ^ - <. o --S 35 r. O 3O f3c* : : rr S. 5-5* 5 jc =. ? ^;3*15 sr 5. = n *n O O fiT 3- r = 3 " s! 3- o ^ ^ ? 2. 5V i O' ^ r- 5 "* S 5 S o' 5--y o o S' * s - a3 Cl Oq _. 5^ 1 c 7> m O T . ^ 2 O O Q. 6* ^ U 2 r. t 3- -- 5* _ n " ' ft < 1 7 O ft * <ro* ls-_ -? O* *< Sfl* < rM '~i'^r S! S' * a"?. 2,q E-o :^o 2 a a. c a* sis _-* =-.S5 n rr t* r-ir r na %nn 5 S O" 0*3 . cT o .3- n"7 f S ^O 3* * E1 5 g. D < o 2H* n ft jt s5.-sft" ?t 2 5 ' = -7?i s I iir. 's-tCj - iV < CO * *1 r -5o a3 --L ^* ^ 2 = ?; ^ ^V . 2 r ii c i-'-s c S'? 2 5<s / nC L: g-* i, ?* cJS H 7*? >*' r- r C ^ = 5' ^ 5-. c* *r l?l * r il i?tu 'o 3| - a < 52 2 2 5'. 3 ?LE ` y (_ S-y l^< I7 frti ?^ 5 * ic ~ s ? r ' ' 2 r~ I '>3 S O < -. i? oO^ 5' E* fi = !,*i Zc ^^s-^ F5|d -n yr r'o 0 n v* o 1 ,, c?* 5--o ^ 2 s = |5 tS | S 5tOC s i'3.^ ;i?-i w3 s3"* io n L?2a aOu3 f<3ft t=3E, go-* 3'cof ti 2o 3-- * ft -r 3 3 O > o 3 Cl o 3 *< **m4 SPI-03093 fr60C0-ldS w - "Ti * . r y s 2 -3 o ' v j^ * Jr 2 2 "5 -3 ~ 5 c . . *j O .i .- <&J c*) ' O e*^ S 3 J2 . >1 rfl Q o i 2g > *j ^ ^ -- *5 o-S --*. s im * a e *" H353 --_<y o2M>'?aCik.-5c5O.---22;2-O.SoJ6*u,**ot2|.c?c,"' cCCvc'3i2x -5 S = C9 -* -c2 .r uy _* 5 oc s| O -C > C' >i Qsrt .X-* .a .X* !* I n =: 3 3 2 3 sj I ' e I e * . -S 8 .a 2s| 0 ?3iE"s:s 1o --'S:JoStO. 0aO-^)1^23Stcoe.S~;-^.SoC-n 'Ze=osCiO5i --->;5, s = |--3^&8Ss S**..Z2 -ro xi t* -- x uocr -5^ 3.- ES g.g' -S S= s--g 3,f * cco 2 jI=TC o?c"u2 5&.i Mt>5cC s^Ss O (N =s t"" E25o iO"sp5E58: vSc2^sc 8 3 s 55; 50 3 E S - " l** S 3 5 f:iiitii-*s 11 =5 11U c " C.S ji Src.x^-3 c = 1 S j = - 3 c ^-g ^ $>~ = ! 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J *3 *" --* Z = urS;*-** ,J c-- C- = * uw ^^ 3 >O U c'J *C CO o >* c in<o It" o *j H E ;: Cuii >.. *<5 .ci.^ y -- y 5 c f* ;1 jS-8 " 0^2:-2 'c i .i: C M 'JL a a * c.f dk . o = _ y ^ tr*3 ^ J? *">_ f- WB5 t: c ci o*I 2 v. o CC OS / m^ ~J 'm3 *- S C *rMV 4 * a * SL3- 3z 5o i- 3*- oc* *--r ^ uc u kJ5? Uo g\ UST. -- - y.1 s 3 C o w *>* -:;co '= a-5 c= --=C-- oar j > z*" S>..= . =ajCe!--.3 0c.a=J >12 3y. -I 2 " ^JJ u ys.. 5= =J "^ .1 3 X ^ Es-* 1 -=SU"i>'>X c = 7. -2 .c i 5~ ? s -|<Jx.2x=Q~ >^X . 1 C = c Ju3/C1C--W^y2.C.t c---<iJ2qoy u4"2* Ss2d--wU 3.Se>j(2 5^-4-- S-5^5- "*.2sco- s.'oU t= 5s ar-, O ^ S: --eE -.-?^> <aa --'Z 35 '_ o _ S -: -f o|: o_i j=' e * t . S? s .S /)tCXj;C ^-=.3iw:5 -*<r..77 M*3m* >>. f5? <5c = .S~^ oX <iijSo <-aZ^5- CE1^X V J9Z <% O J5 > C. (j 3 2 z c. u .j= W u -- ; .j to^4- v : o O; O' " TG ? ' C 'Z * C *C c. 2 c 5X 3^5 o t_ >, c -a c !rt 55 5< .S ^y sm -*2i ^ ui C yC ** - 9Z C 5 ^ >ii.! :/f .2 4*^3^= S g*S ^ 5 = - c.ix % -2--.t 3 . e 3- 23 E - .. .<2 .-- r "2 :r tc" oiJeK^^Tj? ~x-XOZO-j 'iT-. C.S-,-.-r,a: -r ^ o r - u- ' .fcri_- K"S 23a--2 = -;i2<--< > s 2-|J =:^ ^ = S *rj y i ^ Sao- xSjf!fd= JZ==1:=I< ,,;(? Sii.s **d f ~ S - 3 /.-3.2 ali!!l|l =: y - - ft- Z 2. > --Z' C-s T. -- * *r>V 3 o c ,c -r y ^so W?,. < 0^2 2=S ? " >r-; 5.2 K I." S 1-^ Is c 3 >. -- X *o >, c 2 C Sll a^' 2so-s,. ^*y 9600-ldS -- C -3 Vs 5= tf =o u -- ir * ^ S *' -5 -5 i i> < t; ^ = :r~ 5 -= 2Q ^ c ws "T V S d< r2 y >. cc *,r c< 'J CV ^ A i/ir-; /. r ^ s * -- 2 .H -- si 5 o'? i7! so *.sx -- r** g* ft- s>z * si -2* "" c u -3 . :.*3 (-g : S rr -t 4'G ~ jt 52 a Uj a 2 5 -yg .y .>c, " 5*-. aZ. --i_ 3 2*; 23 U? .2 = - 3=! -14 ca V-- 51! J5 3 -- = : 5 t: : *= p-s** <5 >5 S 1> _ X_A -- 0"', r5<\ ~"5Z- C- ur_E <1 s. * -n't; -J o y'"! <y > = = 2 y.u1 hl*; t a. w J g rj > 2 5 ysl-l c o O U. --n y c c - t* CO 2 LO M o Js c u v o > Z. tf> "r5 < Z60C0'ldS -i IIIuC Jj 5||-- rj u. .< c - c5= y Y*6 El V .'5 j? n~. 1l> X 5.t 0^ *x- *cV1*.jk.J. 5 ^3 ^ s jjl ;C 3 1 O e * 5 = -5S -I g -* c * i vt-X0 5*5 %l =* *y & >.*3 si W > 5 u CJ.^ > E -- =2 s c. j . U4~ X0UJ *? - h 3=0 2 OM 7 O1;?. i JO7 ,= 5s vr-tA- .sj^S ; .=*.-2 "7 ?= Se C .2"i -*o3SsS7isi 'Zijl C "* r~X-N^2^33 J 'd xc * r* ifo .. ^V - jv ..*= a. 'o a "3 W 3 C3I = `S* = .I5 ^ i: vi ~h -| <% v 5* - i =z C \ -:< or * r/.: I^2i e X < X *4 .Jiz S- .5 J l\ ^ e ~V o- vox1 1 --c J? c.y1 6i 3A J j .a -2 a: .S e: i 2i =i X'o 2,, 5. *x> co c 0 nn #xrfi * w 2* , .1 2 Ss*b.s ;u 7. - <-S fr"eLp i<s+S3i. ^52-*S:*5.u*^. 33S"! c " 1/ s S!3 sa0><*13o jl J2u4$ 2 .* U tf Z:<.ic-'|'f: 7<jc|<-|-2. ^ .*/> -3: --2 <. -35-2=or-'*;-,rz^r* ; o 2 i & e; 2w a*"; ^u J : , E a*o 1^ 2 .c Cc 5 s s 7. ib?s-ossX E* y* e -3s *ro cc5p..1*?oi9 2^' l Sv ^.:< 5 - c; =5ii *" V > ^ ti t> ' > > S'i^ s5*b SSJ5 tZi5* H.-JS-a Z5< |j 3 i/i ** y ^ -- 5^-= <^* - >Ss= _ iss sj f| SI -, v, 3=^ P* V /, s 4 Jl c 2^ .z ; * ^ Ji<? .x^Ei 2Jq,$aMi = ?.X> X ox x v - V 3-- C x U5 a- 1;^ .!7 |a= <= ** "A X ^ c - $ = c " -X ijs u. i=: ix e-'JK.S ; S- a /! y 2 3 5 *-- s si 2C^; 2-s -- UUtXn * I a^-|^ >> o w z 2 e< Cl e ^ .x z t< ~ S 13 :E xS 4h:a" 5 5k ^O O'-c 5r * tJ '1 ?>a " *TM 3 7 T X. & w :;?v*.-5 :5 ^e ^ s <-*l _ 5fl 7 .n > - ,,u mV * X 7i ^ u {`i `l if HI is "d * 0C 5ii; .5*5 "c'-f *tss.s= !3A a? ^55 3 - -"= S< s _" * , *3 v *V a ^ r !null i . -5"; 3 ~o c r-2X - lllliXee.y^ . .j? sv;^/. : c *!: t > tui//-.;j,x ^.. ^S-S1JfJgu> S" % f ^ Y u 6-5 3 ^ J J c'-t/iXfi?ae *; 5;- l; x 7* -a ia t/$ 1/) 1/1 i/i (/) <^ ^ VI W1 W ^& Vyi y'Si H |K W ^ 5y y j y C y c < ux O >% < "^.3 Ce . => o v 5v Im o > oc .;u5 * o >7=^/3 = 5:5.2^ s Z u**S*3 .3 -Q CJ C <a ^ 5-3 = 7> * OO o V-.-5 .- * 2 2 = S E | -s5i xao. '- < d M~- ^ = _ST ^- y ^ "3 c J^ . ..r. fc-X -- x= 7 ^ M^X 3S >< V;Q> os: ^cg^s ^ri. .3 e-.S5 5 ~. a J.Eu a;=t"i>> 3 y *2.& ; ; <4 P,- ; i^ CC ^ -.OC. Ss * 5-J 151. Viola, P. L. 1970. Pathology of vinyl chloride. Med. Lavoro 61: 174. 152. Viola, P. 1.., A. Bicorn & A. Cai'Uio. 1971. Oncogenic response of rat skin, lungs, and hones lo vinyl chloride. Cancer Res. 31: 516. 153. Vm kiiiimlk, G, F. S/arvas, F. Al Arssii:. H. John & S. Waciitel. 1961. Aufsaugung von Polyvinylchlorid-Pulser dureh die Diinndarmschleitnhaut und deren Abtransport durch die Chylusgel'assc. Dent. Gesundhcilsw. 16: 1727. 154. Von Oi.ttinoln, W. F. 1964. The Halogcnated Hydrocarbons of Industrial and Toxicological Importance. Elsevier Publishing Company. Amsterdam, The Netherlands. 155. Wac.ni r, H. N., Jk.. J. G. McAfee. 1. M. Weiner, M. luo. J. Martinez & W. P. Caini , Jr. 1963. The use of Hg-203 labeled bromomcrcurihydroxyprepane (UMHP) in radioisotope scanning of the spleen. J. Nucl. Med. 4: 190. 156. Wp.pler, W. 1971. 7.ur Mciphologie chroniseher Lebcrkrankheilcn. Leber Magen Darm 1: 45. 157. Wn.ilasts, G. M,, 1. M. Ei.uon A J. H. Wcisulrolr. 1973. Carcinoma after malignant conversion in vitro of epithelial-like cells from rat liver following exposme to chemical carcinogens. Cancer Res. 33: 60R. I5H. Williams, R. T. 1959. Dcloxicjlioti Mechanisms. The Melabolism and Detoxica tion of Drugs, Toxic Substances ar.d Other Organic Compounds. 2nd editChapman A Hall Ltd. London, England. 159 Wilson, R. H. it W. E. McCormick. 1960. Plastics. The toxicity of synthetic resins. A. M A. Arch. Ind. Health 21: 536. 160 Wilson. R. H.. W. F. McCormick. C. F. Tatcm A J. L. Cniroi. 1967. Occupa tional acroostcolysis. Report of 31 cases. J. Am Med Assoc. 291: 577. 161 Wirtsoi.afiek. 2. T. A M. W. Crown 1964. Free radical mechanism for solvent toxicity. Arch. Environ. Health 9: IS6. 162. Win man, I. 1966. Peritoneoscopy. Vols. I A II. Akadimiai 1C1ADO. Publishing House of the Hungarian Academy of Sciences. Budapest. Hungary. 163. Z\rr, }. A., Jr. 1962. Toxic and health effects of plastics ar.d resins. Arch. En viron. Health 4: 125. Disc hssion Dr. H. Buchter {University of Cologne. Grrm.iry); It would seem better for statistical investigations on the reported liver function tests if von could compare the results with similar tests done before the workers came into vinjl chloride manufacturing. Second, in one of the two plants in Germany with incidence of vinyl chloride disease, there is much alcohol intake in the workers- Until now no liver damage has beer, found. Third, in regard lo low lung-function tests, we have not confirmed a pathological diagnosis al all. There should be more discussion about (he cause of this disease, i.c.. whether it is vinyl chloride alone or another agent which may get together with technicJ vinyl chloride, or vinyl aceratc or additives. This may be important in the causation of angiosarcoma. Last, i! has been suggested that liver biopsy be done only after peritoneoscopy because of the risk of bleeding. Dr. M. L. Nfwhouse: May I ask Dr. lelbach how he selected his patients and boss big was tlic exposed group he selected them from? Dr. W. K. Lf.lb.acii (University oj Bonn. Germany): 1 will begin with thr answer to the second part of the question. The whole group is, as far as we know, about 1R0 workers in this plant. We were alerted in December 1972 by Dr. Vcltman's group that patients being examined for skin and bone disease also had signs of liver disease. We examined these patients. l ater wc examined all patients we could bring to the clinic. It is. of course, selected group and docs not permit us to draw conclusions as to percentages. B. Experimental PRELIMIN VIN Vinyl chloride vinyl chloride anu angiosarcoma and in workers expose Angiosarcomas, 2' rats exposed to co 5 days week for death.1 No informatio. at the present time ics of VCM and p to low levels of V< exposed via inh.da conceived the idea pathway, and if s. jugation of VCM PcctcJ. Therefore evaluating these p. Kinetic Studies ol Male Spragueg were exposed to Ppm (0.13-2.99 n depicts the closed. 4 rats were concu only the nares of t her. Expired carh absorption on an . "as removed frer manometer fitted dual syringe pump The chamber : in-line Mir.in-I in' * These studicAssociation. SPI-03098