Document qdzz2wjZ3kk5vBmv57VXka29R

R&S 108715 BIO-MEDICAL RESEARCH DOCUMENT DESCRIPTION FORM 63 68 69 76 Duplicate in all cards:--^ ffjp' | 000019TT year as-1961- File number [Right justify [Numeric only] Author(s), as Last Name FS (No Punctuation) and coden for journal as JAMA preceeded by one blank space 1 A AA ^ t -T-v/Tb / 20 21 40 c---z-r/ fa - &-- s# hf>fi/L/D , - ! 4160 C^rf'c <'l 7778 VS Sub-Index Code 61 62 Title of Report; end with space-hyphen-hyphen-space. Follow with Index Terms, separated from each other with comma-space. Avoid other punctuation; do not abbreviate. 12 61 62 21 r v-xc/c'y Z !/ S '-- / /'"a..--!/.A? /7>,v 22 ----'-'-"-'X---,---/ --/.-----------`-f---X---'m--^S' ^ I'- . AC 7 23 24 Source (Journal, Vol., Number, Pages, Date ) 12 /' // / / A A-.i.l/V'-// A ;/ 61 62 A 31 / 32 Brief Summary 12 10 SUMMARY: 61 62 61 62 63 64 g V iB O V Welwyn Garden City Hertfordshire AL7 1HD Telephone Welwyn Garden 23400 (STD Code 07073) Telex 264251 From J Stafford Division Manager Health & Environment Protection To See Circulation Selow copies to IV^i ^nemicai Industries Limited Plastics Division Your ref. Our ref Tel ext ~ Date JS/MJE/DSO-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 have 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. Circulation Dr W G F Adams Dr B Bennett Dr D P Duffield Dr G Pigott Dr M Sharratt Dr P Grasso 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 SAIC 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) ROUGH TRANSLATION PNEUMOCONIOSIS AND PVC On00; 90 Paper to be published soon by P Lazard, G Guigou, C Capo, P Pommier de Sar and J Berrod Mr S A aged 53 years was admitted to hospital on 26 March 1978 in the care of Dr Guigou, lung specialist (pneumophthisiologue?) in the Digne Hospitc (Haute-Provence Alps) with symgtoms of moderate dyspnoea, diffuse chest pains and a slight fever of 38 which had persisted for a few days. R&S 108717 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-rayexamination 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 microscope 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). 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 ICI. The reader will find in the original article published in the review "Thorax" 1978 Vol 33 pages 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 bagging 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 had 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. H &S lU ttM B R&S 108719 ----------"- The Works Medical Officers of the VCM polymerisation factories who were 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. LAZAP.D - G. GUIGOU - C. CAPO et P. POMHIER DE SANT PNEUMOCONIOSE et POLYCHLORPRE DE VINYLS J. BERROD 30 </) o CD o Monsieur S... A..., age de 53 ans, est hospitalise le 26 Mars 1973 dans le Service du Docteur GUIGOU, pneuraophtisiologue a l'Hopital de DIGNE (Alpes de Haute-Provence) pbur dyspnee moderee, douleurs thoraciques diffuses et febricule a 33 persistant depuis plusieurs jours. Dans les antecedents recents, on note chez cet homme - dont la profession est celle de berger - un episode pulmonaire aigu en Aout 197^> rapidement gueri par une antibiotkerapie de courte duree. II s'agit, en outre, d'un fumeur de longue date, avec une consoramation de 20/30 grammes de tabac par jour. On ns releve pas d'antecedents pathologiques. L'exaraen clinique est negatif 1*intradermo-reaction a la tuberculine positive, et divers examens biologiques dans les limites de la normale. La recherche de 3K est negative. La radiographie pulmonaire montre une image reticulo-nodulaire nette et diffuse (cliche). L1 interrogatoire du malade attire 1*attention sur les occupations professionnelles anterieures. En effet, M. S... a travaille 23 ans dans une usine de produits chimiques. Pendant ces annees, il a ete pratiquement cor.tinuellement affects 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 un travail de berger 7 ans avant son hospitalisation. Aucune etiologie precise ne pouvant etre retenue, M. S... est adresse pour des examens compiecentaires au Service du Professeur CKARPIN a l'Hopital Sainte-Marguerite a MARSEILLE. Etant donne la profession actuelle du malade, la recherche de precipitines seriques est effectuee par immunoelectrophorese et par la raethcde de_ precipitation immuno-chinique d'OUTCHERLONY. Les resultats transmis par le Laboratoire du Professeur MOLINA a CLERMONT-FERRAND font ecarter le diagnostic de pouraon de fermier. La liaison etablie avec le Medecin de l'usine ou avait ete employe M. S... permet de retrouver a l'examen radiophotographiaue systematiaue de 19o7 et 1963 des images reticulc-nodulaires semblables a celles de 1975. Les radiophotos anterieures etaient normales. Une ponction biopsie pulmonaire au trepan pneumatique de Steel est pratiquee; le preleveraent est examine au microscope optique et electronicue. Les prelevements sont confies ensuite au Laboratoire du Professeur PAYAN. On note au microscope optique une infiltration diffuse avec des histiocytes et des cellules geantes multi-nucleees avec quelques formations de collagene /... R&S 108721 2- * L' etude ultra structurale mor.tre des particules etrangeres dans les macro phages. Ces particules sont tres comparables a des grains.de PVC vus au microscope electronique et ne sont pas colorees par les methodes usj^^l Ces -ernes grains de PVC ont ete mis au contact de macrophages alveolaires humains obtenus par lavage bronchiaue. L'examen au microscope electronique de ces macrophages montre 1'apparition rapide de particules de PVC dans les phagosomes (cliches). -- La comparaison des images ainsi obtenues avec les coupes histologiques de la biopsie pulmonaire paraissent suffisamment nettes pour aue le diagno tic de pneumoconiose par inhalation de poussieres de PVC soit tres forteme. evoqu-5. Nous aurons sans doute ulterieurement la confirmation du diagnosti acres examen ds coupes colorees selon la methode originale du Docteur PIGO toxicologue des ICI. Le lecteur trouvera dans 1'article original publie dans la revue "TEOPAX", 197S - 33 - 19-25 par A. APIJAUD et coll-. , une discussion a propos de ce ca; et une bibliographie. En ce qui concerne la Medecine du Travail, nous nous sommes attaches a reconstituer la carriers de cet ouvrier et a preciser les conditions de travail susceptibles d'avoir provoque une pneumoconiose. ; M. S... a ete embauche en 19^5 et, tout de suite, affects dans 1'unite de polymerisation comae conducteur d'essoreuse, puis reeponsable pendant : plusieurs annees d'un sechoir a plateaux dans lequel les operations de nettoyage de filtres a poussiere se faisaient tres frequemment; l'impls^ tation de ce sechoir le situait dans la zone d'ensachage du produit. Ce poste de travail etait nettement plus exposant au risque que le poste d'ensachage proprement dit et un tres petit nombre d'ouvriers y etait affects. Le PVC, fabrique a i'epoque dans cet atelier par le procede en emulsion, etait tres pulverulent et produisait un empoussierage importax (particules de PVC de dimension moyenne : 15 microns avec des "fines" de dimension bien inferieure : 2 a 3 microns). II n'y avait pas de composants associes a ce produit au stade final. En outre, il existait une certaine proportion de monomere. Les moyens techniques de surveillance de I'epoque ne permettaient pas une mesure chiffree de ces risques. Cette exposition a dure environ l6 a 17 ans. 2 a 3 ans avant de quitter l'usine, cet ouvrier etait affecte a un travail d'entretien dans une partie differente de 1'installation, ne comportant pas le meme risque d'empoussierage. Par la suite, les unites de sechage et d'ensachage out ete tres nettement ssparees et 1'automatisation a supprime le travail de nettoyage des filtres a PVC. II est a noter aue les images radiographiques reticulo-nodulaires diffuses signalees en 1967-68 ne sont apparues que 1 a 2 ans apres la cessation de l'exposition aux poussieres. II n'a pas ete retrouve d'antecedents patho^^ lcgiques particuliers pendant toute cette activite. Consommation habitu^Je de tabac, environ 20 a 50 grammes par jour depuis 1'embauche. .../... -3- II n'a pas ete possible de retrouver trace d'examens spirometriques. Sur le plan clinique, on note qu'en'1975 cet homme ne presente que des troubles respiratoires discrets difficiles a dissocier de ce qui peut etre impute a son tabagisme. Sur le plan epidemiologiaue, on peut noter la rarete de petreilles obser vations. Dans l'usine consideree, 1'etude de 150 dossiers radiophotographiques de responsables au sechage ou d'ensacheurs de PVC, longtemps exposes, n'a pas rnontre d'images semblables. Les Kedecins du Travail des usines de polymerisation de CV consultes n'ont pas releve d*images pulmonaires evocatrices de ce type parmi le personnel surveille. La pratique des examens radiophotographiques est systematique dans ces usines pour tous les ouvriers exposes au risque CV et PVC. II faut noter, par ailleurs, que les conditions de travail ont notablement evolue, qu'une dizaine de personnes au total se sont trouvees exposees de la meme maniere que M. S... sans avoir presente d1images pulmonaires anornales et que le produit fabrique en emulsion est particulierement fin, avec de tres petits grains de PVC. Enfin, la discretion des signes fonctionnels et les faibles perturbations des epreuves respiratoires fonctionnelles laissent a penser que la part de la fibrose est tres moderee, difficilsment dissociable du tabagisme. II semblerait done plutot s'agir d'une image de surcharge. Quoi qufil en soit, il apparait que l'examen radiophotographique des personnels ainsi exposes doive etre systematiquement poursuivi, plus speci lement pour le personnel expose a des proauits a grains tres fins de PVC, associe a dss epreuves fonctionnelles respiratoires simples. -T---r--a--v---a--i-l----r--e--a---l-i-s---e-----e--n----c---o---l-l-a--b---o---r-a---t-i--o--n-----a---v--e--c- : - les laboratoires d'Anatomie Pathologique (Prof. H. PAYAN) d'Xmmunolcgie (Prof. R. DEPIEDS) - et la clinique de Pneumo-Phtisiologie (Prof. J. CEARPIN) de I'E.E.R. medicale de MARSEILLE 2 CO >ao1> ro to .../... r &S 108723 ICONOGRAPHIE FIGURE- 1 Radiographie pulmonaire. FIGURE 3 - Plages d'histiocytes a cytoplasme finement vacuolise, associes a un element plasmodial au cytoplasme identique (Hemalun-Phloxine-Safran. Cr X 50). FIGURE 4 - Le noyau de 1'histiocyte est petit, excentre; le cytoplasme est en majeur< partie occupe par des phagosomes a contours irreguliers, contenant une substance d'aspect floconneux ou granuleux; des fibres de collagene se voient au contact du macrophage (E.M. X 12200). FIGURE 5 - Etude f,in vitro1' d'un macrophage alveolaire mis au contact du PVC pendant 90 minutes. Des particules se sont accumulees dans un phagoso occupant la plus grande partie du cytoplasme; des phagolysosomes plus pet: englobent des corpuscules ovalaires et des granulations reduites de PVC; certaines ont tendance a fusionner (E.M. X 6800). FIGURE 6 - Poudre de PVC constitute de sous-unites ovalaires de tailles variees et reliees entre elles par des particules plus petites (E.M. X 46000). FIGURE 8 - Prelevement biopsique: materiel floconneux, a contours irreguliers, cernes par une membrane dense; phagolysosomes parfois fusionnes (E.M. X 37000).