Document 5kO17OwK38xBmMezaD2RN2oMD
o
the thrombopeny is also so caused, but it is probable that
it deals with a turnover disturbance or an increase in disih- .
tegration in the periphery.
It was observed in the anamnese tht thrto patients re-
* f* '
,
ported recidivisic pain in the left upper abdomto'and one
patient reported pain in the right upper .abdomen and a feel
ing of fullness, as earlier diseases of *fLeber tod Milz," yet
long-time intake of medicines or extreme alcoholism were nb , -
discerned* However, three patients without the sclerodera--.
like skin condition and acroosteolysis had record histories
pointing to a chronic liver ailment (Esophagus varices bleed
ing, splenoral anastomosis;portal hypertonus; esophagus
varices, splenomegaly.). The bromosulfaline retention was
clearly increased, but by comparison the values for serum-
transaminase and-phosphates were for the most ptot nothing
out of the ordinary. This discrepancy could alsb be' proiresu;
in the other ten patients. Four patients h&d esophagus
varices, and in twelve cases splenomegaly was proven scin-
tallgraphically. The laparoscopic and liver biopsy results
of five patients, which were available to us at the end of
1972, showed remarkable agreement: surface area of the liver
clearly or finely waved, capsule fibrosis, increased blood-
and lymph-vessels, histologicaly a slight to clear fibrosis
of the portal system and.indifidual cell necrosis, and slight
coarse fat droplets. The result, that we could further ver
ify at this time let us express the following theory: -Except
see
5-0596
o
7
for the slightly toxic alterations of the liver cells, this
results from the expansion of the connective tissues in the
portal system into the diffuse circulation in the liver. In
advanced stages this leads to an interhepatic block (most like
ly because of the hinderances in the height of the portal
system, possibly similar to a sinusoidal block), with esophagus
varices. It remains to be found if the splenomegaly is only
is a secondary condition or if this primarily the direct, .result
.
of toxic changes.
Of nine patients examined in the lung functions (anamnese,
x-rays, .spirometry, entire body plethysmography, and blood
gas analysis) after references pointed to .mainly restrictive
r
alterations, eight of these patients showed partial insuffi
ciencies. Further research must be undertaken to determine
i if these disturbances can be traced back to the fact that
similar changes occur in the lungs as in the collagen and
elastic supporting tissues of the skin, that is, that a
*
beginning diffuse lung fibrosis is the cause of these dis
turbances.
The Initiating Factor This paper is concerned with an industry-caused.disease,
in which the symptoms include (arranged in order of most common occurrence) thrombopeny, /splenomegaly, toxic liver dcunage, ventilation blockage, circulation obstruction, and skin and. bone alteration. This complex of symptoms has not yet been
see 5-0597
aN
been assigned to a known syndrome. It is unexplained etiologically and pathogenically.
Is it possible to obtain a certain insight in the etiology and pathogenesis by a comparison of our results with those previously recorded in literature? Y/hat is then possible to be the initiating factor?
At a simultaneous pressure and temperature increase, liquid vinylchloride is polymerized to polyvinylchloride with
4
the addition of water and various additives, depending upon the different properties desired. In different countries, independent of the additive type, the Raynaud syndrome and acroosteolysis was present in workers cleaning autoclaves. The symptoms appear so characteristic that it lead in the past year to the disease designation of "occupationallyconditioned acroosteolysis" and was advanced to a diagnosis position (28) It is not assumed that the additives, differ ing by type, country of production and methods, play an import ant role, but the harmful combination of these with the vinyl- ' chloride can not be completely excluded. Therefore vinylchloride, the substance present in the largest amount, be comes the main point of our interests. The monomer vinylchloride is pumped over a closed system of an autoclave. The exit possibilities of the gas - and thus the inhalation possibilities - consist then in more places within the pro duction process:
1. Permeability of the autoclaves (intake and offtake)
see
5-0598
d u rin g p o ly m e riz a tio n and recovery processes
w e ll as p e rip o rta l c e llu la r in filtr a tio n (26).
f"
-
CO
00
H XJ r-H H
H4>
0 E*
(0 0
d O rH 43 t> rH
VO v> 0 xJ H
W *4HH4 ,
CO > d W
0 d O C0
% rH
H > Pi
d o
rH 414
o rH rH d
o O J>> O
P 0
,i4 > Xj
0 iH 0
43 44
0 44
4? H
0 . -d
*H H. O
O ft 0
a0
CO o X*
Ho
44 ft d
d iH
C0 x* >
0
0 43
43 CQ
o
44 d Ov
<H H O o 44
to 0 d 43 aH 44 0 <H ft o o
w
ft d H O w 44
43 to X* d 3 CO 0 0 d X3 0 d H 44 d 0
CO 0 0 >1 o rH ft a
1 E5
0 43 4>
d o
d o H 44 C0 44 H ft
S
0
rl
43 0
44
d 0
H 43
* 0
44 d
4434
H
O0
ft !*
0 P
0d
H tP
> *Mri
H
xJ d 3 to d
CO (0 0 rH o CQ od do ft o
XJ C0 0 rH
O 44
0 0 43 44 d
rl O
V o
0 d ft
c ,3 o
d0
0 Tf rH d O rH
'Go to CO
*rl 0. 44 43
d
d
(0 CO to XJ
d
a >>
O 0H
43 y (0 3
0
d 'O
0 43 44
rH (0 rH 0
d 0 rH d 0 44
o rl 44 C0 44
d 0
rH 43
O 44
ft
a
0o
43 44
u Vt
>* .d. i d
44 d
43 44 d
H
0 <H rl dOd
O
a
o
d w
*
0
(0 d
CO 93
CM K'N
43 * 44 0 d0 o rH
43 0 tH u0 00
0 0 d 0 0
O
ft
d
0 1 4> HO
0
f 0 d
(Q dO
d
H
O 4> O 0 H
w 0 O H 44
0 > W
4H-> O
.43 g
0> 4-> +4 (0
0 4+3} d M
O O u d
d o ft 0
4O3 O
rA
o H 44 d o H w
o
44 p
H
<H 0
0 43 44
44
d 0 43 5
*
d 4H4 % O
CM
0 XJ
oo d * N 44
LA d o
fOf*n,
<0
0O
T-- O 44
do
0 g
0 O
tHo
0 0
43 d
0H
d H
oa
9
0 d
o d 0
to.
<0 0 d 43 44 0
O d -P d *H
o0
44 3
&
CM OJ
to &
a
`d
d rl
d 0 rH
d 0
xJ p0
d
0
0
to d
ud XJ
N
o
d
o
r| Od 0
d u 9 0
0dO
d XJ
d d
d
O a) 0 X*
S0 drl
dd
0 P
d
O 43 0
d0
d 43
o
0 to
so
0 XJ
d o
CO rl H
d
O0
.a > S
1 o "43
(0 a
d
0 0 4>
3 444) (00 ft
Xd^ 0
sdd. Od
d ft
0 dd
0 44
4> df-.
X3
0 44
d3
*
rl rH
od
44
to d d0
01
44 H 0 * d
d 4)
to d
*
H rH
00
ft >
0
0
ft d d 43
.d x3
0 d 'd 0
0o
d H
0
H 4>
C3 C3
dd rH 0
0 d
d * !* d0 H
. 0. 0 'dP H d d-
0 xi
d dd to . K
O (\J
d 0 > o d
ft.
0 43 Tj
1 o d 4-> d 0 o 0 o Xd( o d ft O 4-4
d o
*
d H
d rH 0d
0
rl O 0 4-> O & ,
> r> o rH rH H o 43
rH 4> rl 0
4d4 d 0
O X3 O
0 <
d H O
O rH
H
> d rl
d 0* o to rl d 44
W 0 O ft
0 d rH f> O 4>
0 44
d r--1
. rdH
0.
00 d XJ
d 0
0
5
d &
d
0 r*
d 0
' t
a
H
.43 44
d
d o
44
O. v H
d0 tH .0 00
0 CTN
0 0
0d
ft rl X
xi o
0 4->
d 0 43
d
3
rH
VO w
T3
0do o rH
<H H 43
d 0
a
IS XJ
tHo 0 XJ 0 dH r4H3
d0
da
0 44
*
tdo
d fat ,dri
d P> 0
O
00 d
0
|--O1
.d
0
43
30 0
0
rH >> Rrt
4H-> O d
0
d t0o -d
V Vi
0
i
1
>> d d>
1
.CM i d
0
X3 0 drl da 0 , 44 x03
0
H O ft <H O 44 H 1 1 dco
4434 4434 rl &
.
'
4->
0
0
.
to
d
to d
0H
0d
00
d
xJ 0
0p X0J
rH
43 0
d
a *0d
rrHH 0
0. >
rH
d0 ft X0 a d
0 44
tdo
0
rH Wd
O
43
P
rl
CO
rl
0 o d o 0 d
TJ
d d
d0 >rH i--I 0
43
4->
a H
do
4-H> dd 0 a
0
to X0J dd rH d
43 0
rH
M d d
0
*4rHJ d rOHH d
0
d >
10
I ;/ '
Recently, reports were made concerning skin, lung, and bone tumors and obstructions in the bone structure (27). These results, based on animal experiments, lead again in 1970 to a depression of the MAK (maximum occupation concentration) to 100 ppm (13). It is not yet known to us the regulations concerning ghs concentrations at the occupational site*
The symptoms related in the framework of this disease (Raynaud syndrome, toxic liver changes, obstruction in the . * bone compositions and prenarcotic syndrome) may then be pro duced by vinylchloride. Thus, in the knowledge of the occu pational site we can express the conjecture that long term exposure to vinylchloride is at least a, if not even the -disease-initiating factor* The fact that the name 'Occu pationally-caused acroosteolysis" hints only at a not necessarily determining sym ptom shows that a new name / should be coined* We have proposed the designation "so-called yinylchloride disease" for this syndrome because this disease, influenced by the participation of numerous organs, obtains the character of a system disease.
Pathogenesis The pathogenesis is, as before, unexplained*, On.the
basis of our research we discussed the theory that the disease as a pathogenetic principle in the furthest sense is caused by an obstruction on the connective tissue or the vessel connective tissue* In-addition, as our theory shows that the toxic agent is effective not only per inhalationem, but
see
5-0600
11 al60 perkutan, the fact exists that only uncovered main arteries exhibit scleroderma-like coatings and that the band-like os teolysis is only found on the finger phalanges. We saw sclerOderma-like skin alterations as well as acroosteolytosis only in workers who had worked a long period with the cleaning of autoclaves* This can perhaps be explained by the fact that 600-1000 ppm of vinylchloride could be measured in the area of the autoclave walls (5)* As an indication based upon the obstruction of the connective tissues, we saw the qualitative and quantitative alterations of the skin and the multipli cation of collagenic fibers in the portal system of the liver. The increase and expansion of the capillaries was visible by capillary microscopy and histology in the upper cutis, in addition to the peripheral circulation obstruction proved clinically, angiographically, and thermographicallyi Even
the alteration of the bone (osteolysis as a result of trophic obstruction by damage to the vasa nutricia) and the lung (restrictive and obstrictive ventilation blockage) can be synonomously explained. The prognosis of the disease judged quite optimistically by earlier literature-appears quite serious to us, especially with respect to thrombopeny, 'splenomegaly, and portal hypertension^ According to our observations of alterations in the bone, this disease should be judged with reserve.
Consequences for the Practice The triassic formation of this disease system, serious
see 5-0601
o 12
prognosis and relatively high mortality (from our C iv?nvestigation certainly more than 10%) has led prevailingly youn men to sol
icit ns to place the following suggestions:
1 * Execution of epidemologic and preventative medical experi
mental tests. In our opinion, it is not sufficient any more
to search for only Raynaud syndromes and knotty skin alter
ations because these symptoms , as characteristic as they are,
already show the advanced stage of disease. Perhaps more ^ -
important, controls to determine the thrombozytic count in
regular time periods should be given to all employees of PVC--
producing industries. This should take workers with a con
stant thrombopeny out of this branch of the industry, as this
appears to be the first objective symptom, before further and
more serious internal damage occurs.
2. No employment given to those with liver diseases or circu
latory problems.
3. Regular gas concentration measurements in different work
sites to avoid exceeding the MAK limit. Experienced tech
nical improvement with the goal of greatest possible automation, andimprovement of the ventilation conditions to reduce the
possibilities of gas inhalation to the lowest amount possible.
4. Compensation to diseased workers and recognition of this
disease as liable to indemnity by inclusion in the list of
BKVO.
/
5* More research, especially with animals, using vinylchloride
with special consideration to the skin, bones, lungs, liver,
and spleen.
see ^_0fe02
\
13
BIBLIOGRAPHY:
Litcntuc^
(|J Anpheles.u, l.. M. Otniu. F.. (Vbines^u, L. Hjg'?ira-chi--r>.Mc.,
c Dohniu-uu. V. r.ancj: Convidcraui
e(inico-ptr>;enme 4vianr> fcnomcnului Raynaud li muncm-rn Jin inJu<fru
puliclorurii dc -.mil. Med. interna
xirkularion. FoiKhMi>gsh*rid.e da Lan des NotJrhein-VcMfjleo. Nr. liS ('Vesrdcutsther Verlag: Koln I9M).
(1 j) Julie, 3.. C. Vcliirun: Zur KiiAik der iu|. Vnyl(.lili)nd-K.f*'c.-.erf I. internafinrulct Sfinpouam dcr 7 crlisarztc dcr chcniisAcn Industrie. 27. a. |972.
(Sue.) 21 (lH. 47).
12) Basalaev, A. V.. A. K. Vann. A. C. Kochetkov: On the pathogenesis ot change* developing due to a lungterm exposure lu the effect ot vinyl-
(IS) J'ihe S., C.-E. Lange: Sk:fodermie* artige Hautveranderunfcn. RaynaudSyndrom und Akrontrcolysen bei Arbeitem dcr PVC-hetstellendn Industrie.
OtsJs. mcd. Wtchr. 97 (1972;. 1922.
diloridc. Gig. Tr. prof. Zabvl. U (1972), 24.
(17) Jdhe S., C.-E. Lange. C. Stein. G. Veltman: Zur Klinik der sog. Vinyl-
(J) Cb'eliifl, A.. P. Monllon: Un syndrome d'acro-oitenlj se 4`uriginc
chlond-krankheit. Jahrests pang Oevcsdse Gcsdischaft fur Arbtittmnlain,
pmfeuionclle ct de conststmis nouvclle 24. 10. 1972.
cn France. J. Radiol. Electrol. 41 (19(7), 277.
(18) Lange, C.-E., S. Juhe, C. Stein, G. Veltman: Die sog. VinyUbSorid-
(4) Cordier. J. M., C. Fiwex, M. J.
KranUicit - tine b<(ufsbedgte Syateov
Lcfevre. A. Stnin: AcMoucoIrte et Ihioni cutanea auaeicet ehet deux
ouvrien afteetes is nertoyipe d'autncUvei. Cah- Med. Travail 4 (1964], 1.
sklerose? tnt. Arch. ArbcitsoecL. in Dnidt.
(19) Lange, C.-E.. S. Jflhe, H. J. Marjtejler. R. Mulier, G. Veitgran: Leber-
U) Cook, W. A., P. M. Gver, 1. D.
ichiden im Rahmen der sog. Vinyl*
Dinman, K. J. Magnuson: Occupational dilorid-Knnkhcit. Jahresstgung Deut
acrooKColytis. II. An industrial hygiene sche Gctdlschaft tiir Arbciamedizia
Rudy. Arch. environm. Hlch 22
18. J. 1973.
(I97t). 74.
(20) Mastromatteo. E.. A. M, Fisher.
(0 OiAtigef, H.r Accidental poisoning H. Christie. H. Dinaagcr. Acute inha
by vinyl chloride. Canad. med. Aasue. lation toxicity of vinyl Aloridc to
J. 12 (19(0), 825.
laboratory animals. Amcr. iadustr*
(7) Dintnan, B. D., W. A. Cook, V. M. fi'kiuhauK, H. j. Magnuson: Occupational acmotteoljsis. I. An epidemiological study. Atdi. environm. Kith 22 (1971). <1.
Hyg. Ass.'J. 21 (1960> 394; ikkrt in: Millers, K. E.. R. L. Ziebuss {ed.J: . Industrial Toxicology and Dermatology in the Production and Ptwcesneg of PUwia (Elsevier: Amsterdam 19(4).
(I) Dodson. V. N., B. D. Dinman, W. M. Whitehousc, A. N. M, Nasr, H. J. Magnuton: Occupational acrov
(211 O'Conner, R. A new occupies^ nai disease is born. J. oceup. Med.
` 12 (1970), 234.
Reolysis. ITT. A clinical study. Arch,
(22) Peoples. A. S., C. O. Leake: The
environm. HI* 22 (1971), 83. *
anesthetic action of vinly chloride.
(9) Dublin. L. 2. J. Vaner Occupa
J. PharntacoL exp. Ther. *8 (1933). 284.
tional hiaards aad diagnostic science.
(23! Stein, C., S. Jtihe, C.-E. Lange,
Bunetua No. 322 (1933). Bulletin No. 4( C. Veltman: Bandfdrmige Osrcolyien in
(1941), U.SA. Dept. Labor; xitiert in:
OaAtigtt (S).
den Endphalangen deg Hattdskeienv. Fonsichr. Rbntgenstr. Ilf (1973), (0.
(Ml Filatova, V. S.. L. J. Balakhonov*. (24) Stem. G,, S. Jlihe. C.-E- Langs,
E. S. Gronsbcrg: Hygienicconditions in C. Veltman: Skelcnveranderungea bei
the production uf vinyl chloride. Gig.
der sog. Vinylchlofid-Krankjejt
Tr. prof. Zabol 1 (19381. (-, titicrr in
Rdnrgenpraxii, tm Drudt.
FubUc Health Enpa. Abscr. 40 (19(0) No. 4, p. (.
(25) Suciu, I., J. Drcjtnis, M. Valaskai: Contributii la itudiul imbolnaviriior
(11) Harria. D. K.% Health problems in praduse de dorura de vinil. Med.
the manufacture and use ot plastics.
interna (Buc.) 15 (1>4J,. 9(7.
Brit. J. industr. Med. 10 (1933), 233; tkietf in: Mahen. K. E., R, L. Zielhuis (cd.|: Industrial Toxicology and Derma tology in the Production and Pnacrssirig of Plastics (Ets^vter: Amsterdam 1944)) 143.
(14) Torkelson, T. R.. F. Oyen. V. K. Rowe: The tuaicity of vinyl Aloride * ilcrermintd by repeated exposure to libnratury inimaks. Araer. iadustr. Hyp Ais'. J- 22119(1),'139; utrt In: Malten. K. E . R. L. Zielhais (cJ.):
(12) Karris. D. V... W. C. F. Ad*ms:
Industrial Toxicology and Dermatology
Aero-oiceciMis occurring in men eneaxcJ in the Production and Processing of
in the polymerisation of vinyl AloriJc. Plastics (Elsevier: Amsterdam 19(4).
Brit, tried. |. W7.J. 712.
(27y Viola, P. 1_. A. Bigoeti, .4. CipulO:
(U* Henschler. H. (Hng ): Cesund-
On,ug:nic response of rat slue, lungs,
beiuschadlnise Arbeitstmre. TumVuIo- and bones to vinyl chlorule. Cancer gndwrbe.ismcd t inuche brgrtinuuog von Res. Jt (1971). 3(4.
Keiai 1972).MAK-'X'errcn (1 rriag Chemie. i'cin.
04) Jacoby. H.: Periphre DurdsblurungiVcankbeirits i.n Spiegil dcr Mikto-
(28) Wilson. R. H.. W. E. McComick. C. F. Tatum, J. L. Creeds: Ocrvpjtional jcmosieolysis. J. Amer. med. As*. 201 {196D. S77.
Dr. Susannc luVic. Dr. C.-E. Lanec, Dr. G. Stein. Prof. Dr. G. Vclr^san
Ur.ivcrsicart-Hau'k'inik 5.) Bonn 1. VeiujbcrK
see
5-060