Document Ne4N0ERa7Mq1gbZK2RY9nxJZQ

> PO Box NO 6 3cs30fftQr Rosd Welwyn Garden City Hertfordshire AL71HD Telephone Welwyn Garden 23400 (STD Code 07073) Telex 2642S1 From j Stafford Division Manager Health & Environment Protection To See Circulation Below CopiM to Imperial Chemical Industries Limited Plastics Division $?. e*> > Your rel. Our ref Tel ext Date JS/MJE/DS0-107 3162 12 February 1979 PVC DUST - PAPER BY FRENCH WORKS MEDICAL OFFICERS Several months ago Dr Lazard of Rhone-Poulenc gave me a copy of a paper he and his colleagues were submitting on PVC dust to a French journal. He did not give me the graphs or figures which were part of the paper. I have been waiting to find the whole paper published in print but I have given up and decided to do a rough translation of the text. You may care to hove a copy of this rough translation so that when the paper does emerge you will be able to clip it on to the French text. I hope that the graphs and figures will be self-explanatory when the French paper emerges. ji. T W t' , * **. - Circulation Dr W G F Adams Dr B Bennett Dr D P Duffield Dr G Pigott Dr M Sharratt Dr P Grosso Dr J T Carter Dr D W Plester Dr G Paddle Sir C Lawrence-Jones Dr F W Best Mr G J Sleddon Mr W Adams Mr R Hards Mr A E H Williams Mr T L Phillips Dr E Lloyd Jones Mr T W Moffitt Mr H M Clayton Mr- M J S Gibbons, ICI Americas Dr J Conbere, ICI Americas Mr A G Wheeler, ICI Americas Dr R E Davies, ICI Melbourne Mr K H White, Duperial 5AIC Dr T Bougas, AECI Dr T R Torkelson, Dow Dr M N Johnson, BFG Mr R N Wheeler, Jr, UCC Mr Waveland Davis, Goodyear Dr D B Douglas, EMAS Dr P Baxter, EMAS Dr M Greenberg, EMAS Dr R Owen, TUC JS (10) R<9Uttr*d m Engiond No. 218019 RogtrorM Other Imowtai ChwnicW Houtt. Miiioan*. London SW1R 3JF r - *, ^ - UCC 010882 ROUGH TRANSLATION PNEUMOCONIOSIS AND PVC Poper to be published soon by P Lazord, G Guigou, C Capo, P Pommier de Santi and J Berrod , Mr S A aged 53 years was admitted to hospital on 26 March 1978 in the care of Or Guigou, lung specialist (pneumophthisiologue?) in the Digne Hospital (Haute-Provence Alps) with symgtoms of moderate dyspnoea, diffuse chest pains and a slight fever of 38 which had persisted for a few days. In this man's recent history (he was a shepherd by profession), an acute pulmonary episode in August 1974 was noted but this was cured rapidly by a short course of antibiotics. He was also a long established smoker who consumed 20/30 gm of tobacco per day. There was no pathological history. The clinical examination was negative, tuberculin test positive and various biological examinations were within normal limits. The BK test was negative. Chest X-rays showed a clear but diffuse (?) reticulo-nodular image (see photo). Questioning of the patient drew attention to previous occupations. Mr S A worked for 23 years in a chemical factory. In these years, he was almost continuously employed in a VCM polymerisation unit and more especially in a workplace which had risks of exposure to powders. He left this employment to work as a shepherd for 7 years before he entered hospital. Since no precise aetiology could be obtained, MS was sent for examination to Prof Charpin at the St Marguerite Hospital in Marseilles. Because of the occupation of the invalid at the time, research was done on serum precipitins by immunoelectrophoresis and by the immuno-chemical precipitation methods of Outcherlony. The results sent from the Laboratory of Professor Molina to Clermont-Ferrand led to the discarding of the diagnosis of farmer's lung. The liaison established with the factory doctor which had previously employed MS allowed the retrieval from the systematic 1967 and 1968 x-ray examination of reticulo-nodular patches similar to those of 1975. Earlier x-ray photographs were normal. A lung puncture biopsy by Steel's pneumatic instrument was carried out; the section was examined both by optical and electron microscopes. The sections were further entrusted to Professor Payan's Laboratory. In the optical microscope one could see a diffuse infiltration with histiocytes and multi-nuclear giant cells with some collagen formation. The electron microscope study shows foreign particles in the macrophages. These particles are very like particles of PVC seen in the electron microscop and are not coloured by the usual methods. These same particles of PVC have been put in contact with human alveolar macrophages obtained by bronchial lavage. The examination by electron microscope of these macrophages shows the rapid appearance of the PVC particles in the phagosomes (slides). 2 The comparison of the pictures obtained thus with the histological sections of the pulmonary biopsy seemed sufficiently clear to suggest very strongly the diagnosis of pneumoconiosis by inhalation of PVC powder. No doubt we will have through time the confirmation of this diagnosis after the examination of sections coloured by the method of Dr Pigott, a toxicologist with ICX. The reader will find in the original article published in the review "Thorax" 1978 Vol 33 poges 19-25 by Arnaud and his colleagues, a discussion of this case and a bibliography. So far as the Works Medical Officers are concerned, we are eager to build up a picture of the career of this worker and to determine precisely the conditions of work which could have given rise to a pneumoconiosis. Mr SA was recruited in 1945 and immediately became occupied in the polymerisation unit as an operator of a drying machine, then for several years was responsible for a plate dryer, the operation of which required the frequent cleaning of powder filters; the location of this dryer put him in the bogging zone for the product. This job was clearly more exposed to risk that the job of bagging itself and a very small number of workers were thus employed. The PVC made at this time in this particular factory by the emulsion process was very finely divided and produced a lot of powder (the particles of PVC had an average size of 15 microns with "fines" of a very much smaller size viz 2 to 3 microns). There were no other compounds associated with this product in its final state. Of course there was a certain proportion of monomer. The technical means of surveillance at the time did not permit an accurate measure of these risks. This exposure lasted about 16 to 17 years. 2 to 3 years before he left the factory, this worker was engaged in maintenance work in a different part of the installation, which didn't have the same risk of powder exposure. Later on the drying and bagging units hod been quite clearly separated and automation has eliminated the work of cleaning PVC filters. It should be noted that the diffuse reticulo-nodular patches in the x-ray photographs in 1967-68 didn't appear until 1 or 2 years after stopping exposure to powder. There were no specific prior pathological symptoms found during the whole of this activity. The man's normal consumption of tobacco was around 20-30 grammes per day during his employment. It was not possible to find any trace of lung function tests. In the man's records, one notes that in 1975 he did not show any particular respiratory problems except those connected or that could be imputed to his tobacco usage. In epidemiological work, one can see how rare such observations are. In the factory in question the study of x-ray photographic records of those in drying and bagging PVC and exposed for a very long time have not shown similar features. r ucc 010884 3 The Works Medical Officers of the VCM polymerisation factories whowere consulted have not noticed lung pictures of this type among their employees. X-ray examinations are done regularly of all workers exposed to the VCM and PVC risk in these factories. In addition it should be noted that the working conditions have changed greatly, that around 10 persons in total have been exposed in the same manner as Mr SA without having given any abnormal lung pictures and that the emulsion product is particularly finely divided. Finally, consideration of the functional symptoms and the small perturbations in lung function tests leads one to think that the amount of fibrosis is very limited and difficult to dissociate from the use of tobacco. It would seem therefore a question of an additional burden. Be that as it may, it appears that x-ray examination of employees exposed in this way must be systematically pursued, more especially in the case of employees exposed to fine PVC dust and this must be done in association with lung function tests. JS/MJE/DSO-107 9 February 1979 P. LAZARD - 0. GPIGQtT - C. CAPO et P. POMMIES DE SANTI - J. BERROD PNEPMOCONIOSS et POLYCHLORPRE DE VINYLS Monsieur S... A..., Sgi de 53 ans, est hospitalise le 26 Mars 1978 dans le Service du Docteur GUIGOU, pneumophtisiologue a l'Hopital de DIGNE (Alpes de Haute-Provence) pour dyspnee raod&ree, douleurs thoraciques diffuses et febricule a 38 persistant depuis plusieurs jours. Dans les antecedents recents, on note chez cet bomme - dont la profession est cells de berger - un episode pulmonaire aigu en Aoflt 197^, rapidement gueri par nne antibiotherapie de courte duree. :; II s'agit, en outre, d'un fumeur de longue date, avec nne consommation de 20/30 grammes de tabac par jour. On ne releve pas d'antecedents pathologiques. L'examen clinique est negatif, l'intradermo-reaction a la tuberculins positive, et divers examens biolo- giques dans le3 limites de la normale. La recherche de BK est negative. La radiograpbie pulmonaire montre une image reticulo-nodulaire nette et diffuse (cliche). i L* interrogators du malade attire 1'attention sur les occupations ' professionnelles anterieures. En effet, M. S... a travaille 23 ass dans une usine de produits chimiques. Pendant ces annees, 11 a ete pratiquement continuellement affecte dans une unite de polymerisation de Chlorure de vinyle et, plus specialement, a un poste de travail comportant des risques d'empoussierage. II a quitte cet emploi pour an travail de berger 7 ans avant son hospitalisation. Accune otiologie precise ne pouvant etre retenue, M. S... est adresse pour des examens complecentaires au Service du Professeur CHARPIN A l'Hopital Sainte-Marguerite a MARSEILLE. Etant donne la profession actuelle du malade, la recherche de pricipitines seriquea est effectuee par immunoAleetrophorise et par la methods de precipitation imauno-chiaique d'OOTCHERLQNY. Les risultats transmis par le Laboratoire du Professeur MOLINA a CLERMONT-FERRAND font ecarter le diagnostic de poomon de fermier. j La liaison etablie avec le Meaecin de 1*usine ou avait ete employe M. S... nermet de retrouver a l'examen radiophotographique systematique de 1967 et 1968 des images reticulo-nodulaires semblables a celles de 1975. Les radiophctos anterieures etaient normales. Dr.e ponction biopsie pulmonaire au trepan pneumatique de Steel est pratiques; le prelevement est examine au microscope optique et electronique. Les prAlevements sent confies ensuite au Laboratoire du Professeur PAYAN. Cn note au microscope optique une infiltration diffuse avec des histiocytes et des cellules geantee multi-nucleees avec quelquea formations de collagene. / ucc 010886 -2- L' etude ultra structural# montre des particules AtrangAres dans les macro phages* Ces particules sont trAa comparables & des grains de FVC true i^^Sfe****^ au microscope Alectronique et ne sont pas colories par les methodes usuelles^^t^' v:- ... Ces mimes grains de PVC ont AtA mis au contact de macrophages alveolaires humains obtenus par lavage bronehique. L'examen au microscope Alectronique de ces macrophages montre 1'apparition rapide de particules de PTC dans les phagosomes (cliches). y * * * La comparaison des images ainsi obtenues avee les coupes histologiques de la biopsie pulmonaire paraissent suffisamment nettes pour que le diagnos tic de pneumoconiose par inhalation de poussiires de PTC soit trAa fortmeat AvoquA. Nous aurons sans doute ulterieurement la confirmation du diagnostic aprAs examen de coupes colories selon la mithode originals du Docteur PIGOTT1':toxicologue dea 1CI. . ` Le lecteur trouvera dans 1'article original publie dans la revue "THOBAX", ;'v 1973 - 33 - 19-25 par A. ARNAUD et coll'., une discussion A propos de ce cas .. . et une bibliographic. En ce qui concerne la MAdecine du Travail, nous nous sommes attaches a reconstituer la carriers de cet ouvrier et a preciaer les conditions de travail suseeptibles d'avoir provoquA une pneumoconiose. K. S... a ete embauche en 19^5 et, tout de suite, affecte dans l'unite de polymerisation corame eonductsur d'essoreuse, puis reeponsable pendant plusieurs annees d'un sAehoir a plateaux dans lequel les operations de nettoyage de flitres a poussiere se faiaaient tres frAquemoeat *, 1'implan tation de ce seehoir le situait dans la zone d'ensachage du produit. Ce poste de travail etait settement plus exposant au risque que le poste d'ensachage proprement dit et un tres petit nombre d'ouvriers y etait affecte. Le PVC, fabrlque a I'Apoque dans cet atelier par le procede ca emulsion, etait tres pulverulent et produisait un empoucsierage important (particules de PVC de dimension moyenne : 15 microns avec des "fines" de dimension bien inferieure : 2 a 3 microns). XI n'y avait pas de composants associes a ce produit au stade final. En outre, il existalt une certain# proportion de aonomdre. Les moyens techniques ds surveillance de l'Apoqu* ne permettaient pas une mesure chiffree de ces risquss. ' Cette exposition a dure environ 16 a 17 ans. 2 a 3 ans avant de quitter l'usine, cet ouvrier etait affecte A un travail d'entretiea dans une parti different# de 1'installation, ne comportant pas le m$me risque d'empoussierage. Par la suite, les unites de sAchage et d'ensachage oat ete tres nettement separAes et l'automatisation a supprimA le travail de nettoyage des flitres a PVC. II est a noter que les images radiographiques reticulo-nodulaires diffuses sigoalees en 1967-68 ne sont spparues que 1 A 2 ans aprAs la cessation de 1'exposition aux poussieres. XI n'a pas AtA retrouvA d'antAcedents patholcgiaues partieuliers pendant toute cette activit*. Coasommation habituelle de tabac, environ 20 a 30 grammes par jour depuis 1'embauche. *../... ucc 010887 5- II n'a pas eta possible de retrouver trace d'examens spirometriques. Sur le plan clinique, on note qu'en`1975 eet homme ne priaento qua das troubles respiratoires diserats difficiles a dissooier de ea qui peut tre impute & son tabagisme. Sur le plan Spidemiologique, on peut noter la rarete de pmreilles obser vations* Dana l'usine consideree, 1'etude de 150 dossiers radiophotographiquee de responsables du s&ehage ou d'ensacheurs de PVC, longtemps exposesi n'a pas montr6 d'images semblables. Las Medecins du Travail des usines de polymerisation de CV eonsultes n'ont pas relevi d'images pulmonaires evocatrices de ce type parmi le personnel surveille. La pratique des examens radiophotographiques eat systimatique dans ces usines pour tons las ouvriera exposes au risque CV II faut noter, par ailleurs, qua lea conditions de travail ont notablement evolue, qu'une dizaine de personnes au total se sont trouvees exposees de la mSme maniere qua M* S... sans avoir pr4sente d'images pulmonaires anornales et que le produit fabrique en emulsion est particulierement fin, avec de tres petits grains de PVC. Enfin, la discretion des signea fonetionnels et les faibles perturbations des epreuves respiratoires fonctionnelles laissent a penser que la part de la fibrose est tres moderee, difficilement dissociable du tabagisme. II semblerait done plutdt s'agir d'une image de surcharge. Quoi qu'il en soit, il apparait que l'examen radiophotographique des personnels ainsi exposes doive 4tre systeoatiquement poursuivi, plus specialement pour le personnel expose a des produits a grains tres fins de PVC, associe a dss epreuves fonctionnelles respiratoires simples. Travail r&alise en collaboration avec : les laboratoires d'Anatomie Fathologique (Prof. H. PATAU) d'lmmunologie (Prof. R. DEPIEDS) et la clinique de Pneumo-Phtisiologle (Prof. J. CHARPIN) de l'U.E.R. medicals de MARSEILLE ./ UCC 010888 iconoghaphie FIGURE- 1 Radiograpbie pulmonaire. FIGURE 5 Plages d'histiocytes a oytoplasme finement vacnollse, associes a un element plasmodial au oytoplasme identique (Hemalun-Phloxine-Safran. Cr X 250). FIGURE 4 - Le noyau de l'bistiocyte est petit, excentre; le cytoplasms est en majeure partie occupe par des phagosomes a contours irrtguliers, contenant une substance d'aspect floeonneux ou granuleux; des fibres de collagens se voient au contact du macrophage (E.M. X 12200). FIGU3E 5 - Ut.- l* Etude "in vitro" d'un macrophage alveolaire mis au contact du PVC pendant 90 minutes. Des particules se sont accumulees dims un phagosome occupant la plus grande partie du cytoplasms; des phagolysosomes plus petitH englobent des corpuscules ovalaires et des granulations reduites de PVC; T* certaines out tendance a fusionner (E.M. X 6800). FIGURE 6 - Poudre de PVC constitute de sous-unitts ovalaires de tallies variees et reliees entre elles par des particules plus petites (E.M. X 46000). FIGURE 8 - Prelivement biopsique: materiel floeonneux, i contours irreguliers, cernes par une membrane dense; phagolysosomes parfois fusionnes (E.M. X 37000). HV if. ucc 010889