Document 10eL5j5DL1Xg2LjE05mqjJayq

> IMPERIAL CHEMICAL INDUSTRIES LIMITED PLASTICS DIVISION PVC DUST Paper for APME Meeting in Vienno, 9 June 1 Introduction Over the past 1/2 years I have from time to time given brief oral reports at CEFIC/APME VCM meetings on the work done by Dr C Wagner of the Pneumoconiosis Research Unit (PRU) of the Medical Research Council (MRC), a UK Government institution. Dr Wagner found that he could generate Kupffer cell sareomos in rats given intra-pleural injections of emulsion type PVC polymer. On 31 January 1978, the Chemical Industries Association (CIA) had o meeting with various UK Government Departments, the Trades Union Congress (TUC) Medical Adviser and the PRU represented by its new director Dr P Elmes and Dr C Wagner. Partly orising from that 31 January meeting, there was an Ad Hoc Tripartite (ie Government, Union and Industry) Medical Meeting on 5 May at which o serious attempt wos made by our Government Employment Medical Advisory Service (EMAS) to persuade industry to accept a change in the status of PVC dust for hygiene purposes. I thought you should know of this since any action by the UK Government in this field could have repercussions elsewhere. 2 Papers on PVC Dust I attach for your attention a copy of a paper I wrote for 5 May giving a summary of the CIA Meeting of 31 January 1978 (Appendix 1). I also append a copy of a literature summary by Dr M Greenberg of EMAS (Appendix 2). In case you have not seen it, there is also appended (Appendix 3) a copy of a paper by Prof, Arnaud in Thorax (1978 Vol 33 pages 19-25;, a journol whose editorial board includes Dr Elmes and Dr Wagner. (Indeed Dr Elmes drew my attention to the paper.) Dr Garlanda has also given me a copy of a summary in English of the Italian trade union epidemiological survey (Appendix 4; and you will note on page 3 reference to 23 pneumoconiosis cases alleged to have been found in men exposed to PVC dust in bagging operations etc. At the 5 May meeting, Dr D P Duffield gave on oral account of the full chest x-roy studies done by the National Cool Board's radiography unit on 324 ICI workers. He also gave an oral account of recently completed work at an ICI Paints Division plant which compounds and fabricates PVC emulsion polymer. We hope to produce so*e written reports of this work in the near Future despite the fact that we expect our Government to be critical of the work because of inadequate control populations and suggestions that the populations may be of the wrong size and moy count as selected populations. Dr D P Duffield and Dr B W Duck referred to work done by European and US companies on chest x-rays - EMAS were not much impressed since no papers l have so far been published. Dr Duffield and Dr Duck criticised the papers listed by Dr Greenberg as being utterly inadequate. Dr Duck told of his frustrations in trying to speak with Prof., Frongia. Both admitted that the Arnoud paper was the first paper we had seen which was well written and merited really close attention. We were also oware that here and there, now and ogain there UCC 010987 hove been isolated single cases of some pulmonary problems which could conceivably be associated with PVC dust. We also know of the University of Louisville's ongoing research into pleural plaque formation in a group of BF Goodrich employees who have been exposed to a number of chemicals including, we believe, VCM but we are uncertain whether they were exposed to PVC dust. We could not believe that 23 pneumoconiosis cases could have occurred in Italy without our Itolian friends having told us about them. The TUC Medical Adviser had no information on this point from Italian unions. Moreover we had not hod an opportunity so far to inspect or assess Dr Wagner's work on which we have had only interim, oral reports. Furthermore no one knew the significance of intra-pleural injection of any particulate matter as a technique for prediction of ill effects in man and Dr Wagner's latest experiments on PVC dust inhalation must be recognised os difficult work to interpret and monitor both with regard to concentrations of dust and the combination of inhalation plus ingestion which occurs. EMAS thought there had been sufficient indications over the post 4 years to cast some doubts on PVC dust. In their view there was increasing evidence that the retention of PVC polymer was not a benign process. EMAS moved awoy from their position of 31 January and suggested to us that the TLV for PVC dust should be reduced from 10 to 5 mg/m . We would not accept that there was sufficient medical or biological evidence to worront such a change. As an alternative EMAS thought that o "best practicable meons'* approach may be required to improve hygiene. Monitoring of course is a problem here - our measuring methods relate to occasional sampling ond we may have to adopt to a sequential monitoring system os for VCM, There will be further discussions on this matter in June and we can safely predict that our Government and Unions wjli not be easily satisfied. We are trying to get our work properly written up ond presented to EMAS and we will need to improve on measurement procedures. We will discuss yet again with EMAS the need for a morbidity ond or mortality study, particularly in the PVC fabrication industry. I am confident that we con take care of these motters in the PVC manufacturing industry if there is on insistence on a best practicable means approach - I am apprehensive about the ability of some ports of the PVC fabrication industry to cope with eg dust monitoring, (in the lost day or two I have heard thot EMAS have been called in to one of our larger customers and it is alleged a high level of emulsion polymer dust 40 mg/m was found.') Liver Angiosarcoma in the PVC Fabrication Industry EMAS are investigating on ASL cose in a man who was employed for over 30 years in plastics fabrication where, it is alleged he hondled polythene, polystyrene and PVC. EMAS were not in a position yet to discuss detail with us but already they were beginning to adopt a stance thot there is growing suspicion that low levels of VCM may give risk to ASL. We could not ogree that there was "growing suspicion" of this sort. I do not think this ASL ease was affecting the EMAS judgement on PVC powders. J Stafford Division Manager* Health & Environment Protection JS/KJE/DS0-107 11 May 1978 ucc 010988 IMPERIAL CHEMICAL INDUSTRIES LIMITED J PLASTICS DIVIjION 'ppe" Drv i paper tor emas meeting, 5 may 1978 at regina house PVC DUST 1 Sugary Note on Meeting with MRC Pneumoconiosis Research Unit 31 January 1V/8 Introduction Under CIA auspices, a meeting was held on 31 January 1978 with H5E, EMAS, DHSS, TUC, BIBRA and CIA representatives present to discuss the MRC work on PVC dust. The following points arose. (a) Dr Wagner of the MRC in August 1975 gave 48 rots a single intro pleural injection of 20 mgm of PVC emulsion polymer in saline. Between 12 and 18 months, 9 onimals died and of these 5 had liver tumours. Pathologists agree 3 tumours were malignant, arising from Kupffer cells. One tumour occurred at the injection site. Nothing further was found until rats 33-45 died and showed liver ond spleen fibroses and Kupffer cell damage. 3 animols still survive. In January 1977, Dj Wagner exposed 48 rots to inhale an atmosphere containing 12 mg/m'3 PVC emulsion polymer dust for 7 hrs aay/5 coys week for 5 months. In June 1977, 6 exposed rats were sacrificed ond evidence found of dust deposition in macrophages_in the alveoli, nrhg~tissue, liver ond spleen.. In Jon'uory T9767 "further 6 rats were sacrificed and found to hove interstitiol fibrosis and multiple ,gro.nyl_omoto in lungs,, aggregates of dust around splenic vessels ond occasional particles in Kupffer cells in the liver. In post mortem examinations of human cases in the Llondough Hospital, Dr Wagner found PVC particles in lungs ond liver of a man who died from Kupffer cell sarcoma, PVC in the liver of a man who died from a liver tumour, PVC porticles in liver ond spleen (and interstitial fibrosis) in a man who died from bleeding oesophagal varices and PVC particles in lungs and spleen of a South Wales factory employee who died of bronchitis and emphysema. (d) Dr Pigott of ICI's CTL described in vitro and in vivo experiments with PVC powders. In vitro, emulsion polymers were cytotoxic when some specific surfactants were left on the particles' surface. Intraperitoneal and intratracheal injection of emulsion polymers into animols showed no response after 6 months. Dr Pigott concluded the PVC powders he had tested in this way were unlikely to produce fibrosis in man. jl'i*' (e) |l ! I v t| Dr Elmes and Dr Wagner thought it was too early for Dr Pigott to drew such a conclusion. Moreover there wos scattered clinical evide~;e in tne literature to support the possibility that PVC dust may be fibrogenic but Dr Elmes agreed an epidemiological survey would be required to'prove this. All agreed that such a survey could not be warranted on the basis of the present evidence. ucc 010989 (0 Dr Elmes considers thot PVC emulsion polymer may contain a diffusible carcinogen end the toxic effects ore due to PVC particles and not VC.M. The "material" may be a potential cause of lung fibrosis and olso liver fibrosis end portal hypertension. Dr Elmes was reminded that the NCB Pneumoconiosis Unit has x-rayed 324 ICI exposed workers and found no cases of dust reticulosis. We also know that Shell and UCC inter alia have x-rayed exposed workers with the some result. Dr Wegner made reference to pleural plaque he hod been shown in Goodrich workers the University of Louisville is examining some 2 dozen coses but their task is difficult since the men seem to have been exposed to chemicals other than VCM and PVC. (g) j <1 V,! MRC would like to do further inholotion work in this area and the CIA promised all possible help. The MRC inhalation facilities are over loaded at the present time and work on another strain of rat would be difficult to accommodote. The CIA would examine what if anything they could arrange in this area. Dr Douglas thought valuable information will probably appear from the existing work in 6 months time. 00 Dr Wagner would like to have access to other samples of human tissues to check for PVC particles. He also had plans for o series of interlocking experiments to detect synergism with eg barbiturotes since many of the South Wales workers who developed liver disease were taking barbiturates or large amounts of alcohol but Dr Fairweather questioned the value of such complex protocols. a; The TLV for nuisance dusts in 10 ng/m . Mr Henning considered 1 mg/m for the respirable fraction a reasonable target and urged that it would be prudent to improve hygiene here. In fact the jespirable fraction in bagging and drying oreos averages 1 mgm/m . (Dr Wagner's experiments were done ot 12 mgm/m*) There was no cose at present to change the existing "nuisance dust" classification for PVC. ()) IT was agreed that industry would consider the motters brought up at this meeting end ot an appropriate stage discuss future action with Dr Douglas and Mr Henning. J Stafford Division Manoger Health & Environment Protection JS/MJE/DS0-107 19 April 1978 * HOC 010990 PULMONARY DISEASE IN THE VC.V/PVC INDUSTRIES INTRODUCTION 1. Three potential hazard areas can be defined based on the materials to which workers are exposed, namely 1) the polymerization process, 2) the nixing processes, 3) the fabrication processes. 2. In the polymerization processes there is the potential for a worker to be exposed to monomer and/or polymer, depending on the type of process and the stage of the process to which he is exposed. To this may be added exposure to other materials involved in the reaction and to other products of the reaction. 3. A wide range of materials may be met with in the mixing processes where FVC is compounded to produce the material for the particular --'--ation that the resin is required for. Among them may be nces that in their own right are known to be associated with : respiratory disease. In the fabrication stage, apart from moulding, there may be turning, polishing, welding, bonding, thread-tapping and milling. In these processes a hazard may result if there is thermal degradation or tber is production of fine air-borne particles. SesoisXory morbidity in polymerization workers 5. Miller et al (1975) studied pulmonary function in workers exposes to vinyl chloride and polyvinyl chloride and demonstrated high prevalence e of air-flow impairment which increased with age or years of exposure. 5. continued They commented on other possible factors and stated that furtftr study would be required to elucidate the effect of general environmental pollution* To date further studies have not been reported by then. Is a further analysis, Hiller (1975) separated the effect of occupational exposure and found it to predooinate over the effects of smoking. 6. lilis et al (1976), studying a larger group, observed chest x-ray change and pulmonary function abnormalities that did not always correspond with each other. Respiratory symptoms were also stated to be more common* 7- Vfegman (1975) in a conference discussion referred to a small population said to have a pure PVC exposure. Among abnormalities noted three had chest x-rays with fine nodular changes and four bad abnormal FF/s and three abnormal FVCs. A scientific publication has not yet been received. 8. Suciu et si (1975) described bronchitic symptoms and emphysema in workers exposed to VQi as well as adverse effects on lung vol. ventilation and radiographic abnormalities. They concluded that the pulmonary effects were not as intense as other effects and might be caused by other factors such as dust, acids or bases. I -2- T3CC 010992 9. Gamble J et al (1976) studied vinyl chloride polymeriners sod nicer workers but were unable to repeat the observation of Miller et al. They raised the points of the possible differential migration of susceptible workers from their populations and the shortcomings of the internal comparisons they had made between various work groups that were both exposed to agents that could reduce lung function to account for the disparity with Miller et al 0.975? and with Lilis et si (1976). Respiratory morbidity in PVC mixers 10. No specific studies of workers engaged on the compounding of PVC have been found, other than perhaps that by Ssende, B et al (1970) who published a case report of a granulomatous lung condition in a worker engaged in shovelling PVC dust. Respiratory morbidity and mortality in fabricators 11. Vertkia and Mamontov (1970) studying a group of 96 workers employed on I PVC fabrication reported bronchitis and emphysema and impaired ventilation. X-rays also were said to show unusual changes in an wmI number of workers. They concluded that in all probability these changes were due to the action of adverse workshop environmental factors and more especially to prolonged exposure to PVC dust in high concentrations. '> 12. A study of mortality among PVC fabricators (Chiazze L et al, 197?) does not refer to mortality from non-malignant respiratory disease, excess concentrating mainly on^neoplasas which were very likely gastro% intestinal in males and females and possibly breast and urinary organs in females. Being a proportionate mortality study the conclusions are subject to careful interpretation. -3- TYY' 010993 ( CONCLUSIONS 13* As with many studies, it is possible to pick holes in all the reports cited above. Nevertheless, the huaaa evidence on respiratory effects alone is sufficient to counsel prudence ia exposing workers to chronic inhalation of PVC dust, even if the nnimyi evidence (Popow, 1969; Frongia et al, 19?^; kicharda et al, 1975; Qylwick et nl, 1972; etc.) of respiratory and systemic effects is discounted. H GRLENBEEG BUS (E) An additional well documented case of lung disease in a man who had worked in the bagging area of a VCM polymerisation plant has been reported (Arnaud et al, 1978). X-ray changes, lung function and lung tissue changes resembled those in previous reports cited. I* TYT* 010994 1 * b;s::ct>. ?-*y ARTAUD. A., et *1 (T?*)) THORAX, 3A, "9 c-:ta:l2, ... et ni (1977) j.o.m., <^9, 623 criyicx, B., et al ('972) ROC2M. AKAD. MED. BTAL73T. ^7, 9? FSC.VGIA, N., et al ('>974) H5D. DSL. LAVOHO, 6, 3?1 1"!BLS, J., rt al ('976) 22.- 659 LILTS, R., at al ('976) CHEST, 69, 299 LTLIS D., et al (1975) AM). N.Y. ACAD. SC. 2W, 22 KILLER, A., et al (lO?*) AMM. N.Y. ACAD. SC. 2L, k2 MILLS?., A., ("'975) Errv. HEALTH PERSP. v\ PL?JW, .T., (1909) SOC7.N. AKAD. MED. BlALYST. SUPPLEMENT 2L, :!TCi:i, I -t al (9*75) AN'tr. ".Y. ACAD. SC. PM(, 53 S22?D2, B.. et nl (1970) KED. LAVORO 6^, VERTKIi;, I an- MAMONTOV, R., (1970) GIG. TRUDA FRO?. 2AB0L. W-.1SXf.rf, D ('975) Ai.-f. ff.r. ACAD. SC. 2'iA, ?o , 2? e -5- ucc 010995 \PPEV'DIX 0 //<, i. iy-.v 33, :/ :s Polyvinyl chloride pneumoconiosis1 A. ARNAUD, I*. POM MICK DE SANTI, L. GARBC, H. PAY-\N, AND J CHARP1N From the Clinique lit Pneumo-phnsinln^ie, Hfipita! Sqinte Marzuerue. Marseille and the L ahttrut.nrt tf Anutonrue Parho/oaiquc. Hopital de Is Concepcion, Munitlic, France Arnautl. A., Pommier dc Sami, P,, Carbc, L., Pavan, II., and Charpin, J. (1978). Thorax, 33, 19-25. Pol)tin,)I chloride pneumoconiosis. A 53-ycar-o)rt man. ttlio had beer. exposed for 23 years to polyvinyl chloride (PVC) in the bagping area of a tin;.! chloride polymcrisut.on plant, pres-med with a diffuse niicronodular infiltrate on his chest radiograph. Light microscopy of lung obtained by drill biopsy shotted a diffuse infiltration with histiocytes and niuhinucieated giant cells, with some collagen formation. Ultrastruutural studies showed foreign particles in the macrophages, which were identical with PVC powder viewed under the electron microscope. Incubation of PVC powder with human lung macrophages in vitro showed that the macrophages engulfed the powder to give a similar ultrastructural appearance. Pneumoconiosis due to polyvinyl chloride (PVC) was first described by Siendc tt at. (1910) Several cp'dcmiological studies have since been made, which tend to demonstrate that PVC or vinyl chloride (S'O inhalation may be responsible for abnormalities of pulmonary function and chest radiograph (l.ilis ei a!., 1975, 1975; Miller tt al., 1975, Suciu et a!., 1975). However, histopathoIrviral descriptions of this disease are infrequent. We describe here one such case and a study of the udraviriicture of a lung biopsy specimen. Owe report A Vt-year-ohl man was referred in April 1974 for mscslis.itTofi"'bf_diffjiw_micrpns'dul.ir,chejt radio* graphic abnormalities (Fiit I). Me gave a history uf ibronit productive morning cough for three tors, and for three months he had noticed mild weakness and slight exertional dyspnoea. He had smoked 2u cigarettes a day since age 22. t The patient had worked front November 1945 I| tint.I December I96S in the PVC bagging area of a sin,I chloride polymerisation factory. Since 1969 lie had worked ns a shepherd. A chest radiograph performed in 1968 as a routine factory check-up showed the same micrenodutar shadows. No fur ther invevi.fattens were done. Previous chest radiograph* were said to have been normal. Physical examination was negative. A scratch Nvvf.fk^ftcj ,i pjrt hf tl* ItttieiU ftswlldfyK* Mtlill/il tk > a tu.tt ct tist ta tuberculin skin test was weakly positive Sputum examination for Mycobacicrium tuberculosis on three specimens was negative. The red hiood cell count was: 4 19X10*/!, haemoglobin 1J 2 g/dl, leucocyte count 6 6X 1071 with 40*/. lymphocytes and 60'/, neutrophils; platelets 294X10"/I; erythrocyte sedimentation rate 6 and 2tl mm/h, cholesterol 2 II g/1; total bilirubin 6 nig/l. serurr. alkaline phosphatase 55 Wl; SGOT 25 U/l; SGPT 39 eJ/l. Pulmonary function tests showed forced vital capacity 3 32 1 (expected value 5 29 1); forced expiratory volume in 1 second 2 S2 1 (expected value 389 1). Arterial blood gases. PaOj 84 mmHg; 1`nto. 40 mrHy. pH 7 39, Carhon monoxide transfer fuctur 32 14 ml/min/mmHg (predicted value 3t 75(mi/min/ nimHg) (10 7 mtnol/min/kP.i; 10 6 mm.l/min/ kla) No abnormality was seen on bronchoscopy, A lung biopsy using Steel's pneumatic trephine was performed. i.icht MiCRoscorr The lung specimen was. for the most part, diffusely infiltrated by histiocytes, in which were seen a few alveolar duds I Fig 2) The cytoplasm of these hisdocytcs contained clear vacuoles. Gian; n..hinucicjtcJ ceils w.th vacuolated cytoplasm were also present fFic 3; PAS und i'cun blue stains w.ere negative. Polarised light revealed no intra vascular ihirefringent particles The cells were arranged in a collagen matrix, which wav of thinly fibrillar aspect; a few smooth muscle fibres veere also seen. ucc 010996 I -i , J/7'4H./!, /* /*///////. ''* W,'/f / (/,///><* h \r"n, 4 ucc 010997 X /Wniinf (hliiriiic ILFC'I NO.'S MICNOSCOPY The specimen was fixed with 3 4% glutaraldehyde in a cacodylale hufier: post-fixation was with 3% osmium-tetroxidfe 3 he specimen was then de hydrated in acetone and embedded in Araldue. The sections were cut by a Ueichert ultramicrotome, then stained with uranyl acetate and lead citrate. Examination and photographs were obtained hy Philips EM 300 electronic microscope. The cytoplasmic membrane of the macrophages had thin expansions; the nuclei were small, and chromatin was either irregularly disposed in clumps in the cytoplasm or placed against the nuclear membrane. The cytoplasm was, for the major part, infiltrated hy a non-homogenous material surrounded hy an electron dense mem brane, whose outlines were irregular. This material was either granular or of a fiulfy appearance; the granules were 03 to 0-4 microns in sue (Figs 4 and *). Between the phagosomes, thin cytoplasmic layers covered the organelles; the mitochondria were small in size and had well conserved cristi. The Golgi system was normal. These grams were connected by PVC bridges or hy the interposition of smaller granules of 0-1 micron diameter (Fig. . PitQocytoiit nj PVC powder by alveolar m^crophaits Human alveolar macrophages were obtained by bronchial la^ace. About 2 to 3XIQ1 macrophages were incubated with 0 2 ml of PVC powder for 90 minutes at 37-5C in a mixture of 20% of compound 199* and S0% of fetal calf serumJ. The macrophages were then treated and examined with the electron microscope according to the method previously described. The absorption of the PVC particles in the cytoplasm of these cells was rapidly accomplished. The particles appeared in the phagosomes ax either oval corpuscules or clusters which were variable in size (Figs 7 and g) At this stage, the particles showed no evidence of degradation. Thinly granular lysosomal material was deposited against them. The cytoplasm of the macrophages contained mitochondria, bundles of microfilaments. and multiple lyvasomes. Khtctrtm miewunpy of PVC powder The PVC powder4 was composed of oval grains, whose size varied from 1>5X0 3 to IX0-3 microns. `ArcoVYO, MOuntr. 0> A*ta, Fima Discussion \ In this case of Jiscrcte pulmonary fibrosis associ- 'tiuuivi Fstwur, 75 Fsru. Fraud I > ucc 010998 Fig. J Biopsy iptdmtn; flugy rr.ateriui with irrtgulc' onti-r.fi Surroundtd by a itr.it nt --.b'jnt (H). fkagosomts ert icnf-uent in ploett <_). <V X37 CCV) I UCC 010999 /'</> vtnvl i hi,-title pm tmu.i, -n-i'M, 2.t F.a 6 pi'C ponder made of o a! ubi.eitt o; i triable ire, they art linked toytthtr by smaller parueUs (_). (EM X *6 0001 Fig. 7 In-vitro study el Pi'C particle phagocytosis by an alveolar matrophatt showing oval bodies o/ uneven side with irregular outline, sometimes surrounded by finely granular lysosomal material (*-): mtcrofilamenis (m F). (EM X17 000) ated with a granulomatous reaction the lesions contained particles which cotild not be identified by the usual stains. We suggest that this tnay be pneumoconiosis induced bv PVC inhalation. The chest radiographic abnormalities in our patients are the same as those described by Ltlis ct at. (197a); these authors showed that 4S 6% of workers exposed in their work to PVC dust for at least 20 years have reticular and/or micronodular chest radiographic shadows. The histological lesions we describe are identical with those re corded by Szcndc tt al. (1970), who reported the case of a 31 -year-old man who had worked for 12 months in an environment containing high levels of PVC This patient had severe respiratory failure Pulmonary biopsy showed diffuse fibrosis associated with focal granulomatous lesions wncse cells contained ovoid or polygonal particles These lesions are the same as those experimentally pro voked hy Frongta et of. (1974), who exposed guir.ca-p.gi ano rats from two to seven months in a room where P\ C powder was bagged. Exam ination of me gj.nea-pics showed an earlier reac tion at alveolar level composed of macrophages anJ ji.i it multtnucleated cells. These cehs con tained minute intracytoplasmtc granules, which were not stained by the usual methods. On later examination, these lesions became focal granulo- .4 /Irnottd P. Piuntnu t tii bunli l. Ciurlw.fi Po\on. urn! J ( k^rpm Fig. f Jn*wir<> study of an alveolar macrophage in contact with P`C for 90 miuift <* Particle? of PVC art accumulated in c phagosome, ivhuh occupies almost alt of the cytoplotm (,^). Smaller phagosome? engulf oral corpusculet and smalt granules of PVC. (EM XMOO) mas. Examination of rats showed more pro nounced imtuil fibroin: lesions but later lesions were comparable with those observed in the guinea-pigs. The identical morphology of the intracellular foreign particles observed in our patient, and the microscopic appearances of the PVC powder and of the inclusions m human macrophages which have engulfed PVC powder in viiro, are convinc ing evidence that our case can he considered to be that of PVC pneumoconiosis. Clinically, the evolution of PVC pneumoconiosis is uncertain. Our patient had only a slight reduc tion in vital capacity with no reduction in gas transfer factor, suggesting that the fibrosis was not as yet of much functional significance: on the other hand. Sicnd* and co-workers (1970; reported a case with severe respiratory impairment. Occupa tional exposure to PVC dust may have been dif ferent in these two eases. Our patient was exposed to PVC dust only, while Lilts tt al <1975. 1976) showed that PVC dust inhalation induced less severe respiratory function abnormalities than simultaneous inhalation of vinyl chloride monomer and PVC. This must be compared with the results described by Prodan n ei (1975). who showed that, in the guinea-pig, two hours' inhalation each day of air containing lOy, vinyl chloride monomer Over two weeks could produce diffuse pulmonary fibrosis. Further studies of the mechanisms of this pneumoconiosis are in progress. We thank Dr. Allan Towne and Dr. Christian Capo for their help. References NF.-j.".j..i. binr.jiaolu. A., and Du-art!':. A . ,s"-i Cesium polmoiiari spcnmcntali da inaiari.me prounsaia -!i PVC in ainbicnic ili la-oro Aft-imna Jr/ imero. 4$, JII-J41 Lili-. R . Anderson. H . Nicholson. W. J.. Dsu-n S.. Fischbcin. A. S., and Sehkoff. 1. J. (1975). Pnrsa- iI ucc 011001 Pftlyvmyl ih!nrttiv pntumnt'tu Wncc f .i/tiong virtvl chloride Ami poK- I chh>rJc Morkcrv /(mui!\ ttf the .Yen* ) otL i/etnt "/ Stivtue\, 246 22 41 i.Wv H , AtuK-ruui. W , Miller. A , and Selifcoff. J. J (W76> l\il nuiur> change* *niu<i, mh>1 chloride fK`l>mcrH.'i*Kn workers ( hc\t, 6V, Miller, A., TiMcin. A, 5 . Cluing. M , SclikolT, I. J.. nd W*ishau, I (IV7J). Change* in pulmonary func* m *prk?rt c\powd to \in>l and polywnyj chloride, Anngh tf thf S`+h York Atodemy of Snenett, 246, 42-52 Prodan, L-, SuCiu, I , Pi>laru. V , Ilea. E,. and Pa>eu, L. (1975), Lxpenmenul chrome poisoning *ith vin>I chloride (Monochloruethcne), Annoh of ih* ^*`1 ) >* Atsdem\ v! Vi,''Kr' 246, 159-lf.l. hv' 1., Prolan, L . Uca T,, F,.uuraru A . and L i`474* (iu.iw.,1 nsnifvM.uion* \i\ \n.\[ p*i*ufijna' *</ Ati*- }*// + AitiCfttv t>( e1, 241*. Stende, Ji Laps' K . Nt-mw A. and I'i.-.t.-r A (iv*0i PntLmjconiO'it wl.cJ b> (fie inhafauon of pofynn'l chloride duM 4/rdiuno dtf La or3 it, 41.^4'" Reijucii' for repnni* io. Ur. A. Arnaud, Iripual Samtc Marvueruc. BP29-lj;:74, Manti'.lc C*d*\ 2. Franc*. i 1 if c UGC 011002 K VC > j* r Ci-ivi a *, I i- I VJ ! /*\\~t:!STS OF THE RESULTS of TUT 7P IDEM TO LOGICAL INVESTIGATION CCSTEP OUT IN' ITALY ON' WORKERSENPG5ED TO VCM : The investigation has started on the first days of 1975 and involved approx.two years of work. Plants concerned : - Porto Marchers - Brindisi - Terni - Rat-cnna - Ferrara - Rosignano - Ferrandina - Cagliari - Porto Torres - Bollate - Villadossola - Borgaro Torinese MONTEDISON* MONTEDISON MONTEDISON ANIC SOEVAY SOLVAY LIQUICHIMICA SIR RUMIAN'CA SIR RUMIAN'CA MONTEDISON' (pilot-plant) MONTEDISON (pilot-plant) SIR (pilot-plant) Tt has been considered "exposed" all the workers living or dead,pxposed presently or in the past to vinyl chloride for a minimum period of six months. ' 1 I` ! Vhe investigation has been carried out on 4713 workers,equal) t!o 5l of the exposed onen.lt has been possible to ascertain! the death of 64- workers,but it is not sure that it is a j question of the totality nf the deaths which happened in j workers exposed durir.x the period taken into due consideration (.from starting of production of VCM up to 1975)* Synthesis Enployeers Einploveers Contract Work Contract Work Vpcodifipd Dead * I I presently exposed ex exposed presently exposed ex exposed Total * Total 3.071 1.259 ' 4.713 64 4.787 ./. ; f | i i i I I uco 011003 f f. A i J. l! I! ,Taking into account the fact that "tine of exposure" and * I"level of exposure" change, we have been able to calculate an index of exposure and consequently divide the workers into three exposure classes to be considered indicative. Synthesis ( X of workers Exposure Class* low average high 1.068 2,416 1.107 uncalculated 70 I Clinical instrumental and laboratory investigations Lung: i Hands: i i Liver: X-ray photograph of the chest - | eytologieal examination of expectoration X-ray photograph of hands - ^ photopletismographic of the ten fingers in basis conditions and after cold tost SCOT and SGPT - gamma GT - alkaline I phosphatase - bilirubinemia Urine: 0lood: romplet examination + cytological examination of sediment in case of hematuria 1 l romplct hrmorromorytometrir examination - calculation of platelets j Endothelium: study of the vascular centre of eye bottom i The above information has beer, recorded in an epidemiological filing-card. r.-SfLis X-rav photograph of the chest Stressing of the bronchial filling Report "compatible" with neoplasia Results tbc Others >. 28 % 2 cases (in one confirmed 5,7 % 3S In the single classes of age the frequenry of report" stressing of the filling" increases with time of exposure. 4. r. ucc 011004 o3 (I;-It has been noted,in workers :'.n sacking,drying up and stores, Hi 23 cases of pneumo-oniosis in workers, which suraly have had |no further exposures to organic or inorganic dusts, Cvtolocv of spitting No significant fact has been shown. \-r.~v photograph of hands jXorr.al .Results from fractures Suspected acrostheolisis jCertain acrostheolisis I , Photonlctisnographic exaninati on 4.000 16 S 3-77 workers have followed the basis tracing and 3*666 did the tracing after cold test* I i l During the basis tracinr 150 rases showed pathological nodifieations and 742 did the sane during the cold test* 96 workers (2,55) shewed pathological modifications of the basis trarim; as well as of that eftnr cold test; their distribution in different classes showed that frequency of contemporaneous pathological modification of the two tracings increases in! accordance with the increased exposure, quantified by index as well as by time, I Examination of the eve bottom - This examination has been carried out on 4*066 workers. The more significant results are as follows : | ; sclerosis hemorrhages crossing 4SS 14 63 1 ' i Insofar sclerosis regards, there is no correspondence between ! frequency of report and index of exposure. , Vascular syndrome Among the 3.2l2 workers submitted to X-ray photograph examination 01 hands, photopletismogranhin exam*5-nation and of eye bottom, four workers (0,125) showed contemporaneous pathological modification of the three examinations. 1 * These cases can bo rs? r-cf f.r some manner to a "syndrome 1 ! of vascular type"' ^ UCC 011005 i :p ' % i i i _ 4 Hematology %' l I So signifirant findindsconcerning RBC,hemoglobin and I l/BC have been noted. | I It has been noted 339 cases (7,52) of thrombocitopenia in! statistically significantprogression with e\posurc. I ,! Anal'vsis of urine increase of , > j : l Normal Hematuria Albuminuria Hematuria + Albuminuria Clyrosuria Urobilinuria 3.822 2 37 266 22 63 1S2 83 % \ 5,2 2 ; 5.S 5 ` 9 0,5 5 1,52 40 2 The frequency of the microhematuria resulted in relation | with the index cf exposure. ; I' ' *, -L--i-v--e--r---fu--n--c--t-io--n--s J The more frequent pathological changes are the increase of the garni CT in 28,32 of rases and the presence of hepatomegalia in 44,52 ofrases. I J ; | Among whom in which an important hepatomegalia is noted, * there arc more frequent also the thrombocytopenia,arrostheolisis t j or the patologie photopletismographic value: consequently! a syndrome due to vinyl chloride is to be supposed. I \ ) ?*o rt a 1 i tv Causc| of_death | n* partial total Total Infarct myocardium Other cardiopathies Enrephalonvasculopathy Tumours Traches Lur g 1.3-hrvraal sac Esophagus Stomach Encephalon Bladder Liver ,, 9 2 6 16 1 6 1 1 1 3 4 ! } ! i < i i r 1 ucc 011006 5 Hematic angiosarcoma Adenocarcinoma cholecysts Peritonaeum Cutaneous Testes Leukemia Hodgkin 2 2 Chronic aggressive hepatopathy Renal failure Other causes 5 3 8 Not taken into due consideration (Temi plant) 2 30 16 2 64 It appears from the above that among workers exposed to vinyl chloride the cause of death "tumour" is quite more representative if compared with the expectations. i F.M/Lu 20th Febr.l?78 i- ucc 011007