Document zdY5350OdZMjnBM8LL0rB9pNn

4/ Ergebnisse der Inneren Medizin und Kinderheilkunde Advances in Internal Medicine and Pediatrics Neue Folge Herausgegeben von P Frick G.-A.von Harnack K.Kochsiek G. A. Martini A. Prader Mit 24 Abbiidungen und 23TabeIIen ir i Springer-Verlag Berlin Heidelberg New York 1981 N HK O o nr:: BFG09633 Vinyl Chloride-Associated Disease W.K. LELBACH and H J. MARSTEtLER ' 1 Introduction 2 Tewhnolopcal Details.................................................................................................. 2.1 Vinvl'Chlonde Monomer (VCM)................................................................... 2.1.1 History........................................................................................................ 2..2 Production of VCM........................................................................... 2.2 Production of Polyvinyl Cltlonde iPV'C)...................................................... 2.2.1 Technology of Polymerization........................................................... 2-2.2 Methods of Polymerization............................................................... 2.2.3 Compounding................................................................................... 2.2-4 Sources of Exposure to VCM :n PVC Production......................... 2.2.5 The Explosion Hazard....................................................................... 2.2.5 The Odour Threshold \.................................................................... 2.2.7 VCM as an Anaesthetic Agent........................................................... 2.2.8 Effects of Acute Overexposure in Man............................................ 2.2.9 Monitonng VCM Concentrations in Working Areas....................... 2.2.10 Exposure to VCM in PVOProcessing (-Fabricating) Plants.......... 2.2.11 National Standards for the Control of Exposure.................... 2.2.12 Exposure to VCM Outside the Working Area................................. 4 4 a 5 6 6 7 S 8 9 10 10 11 13 15 17 18 3 Toxicology of VCM.............................................................................~........... 3.1 Acute Toxicity.................................................................................... 3.2 Chronic Toxicity.................................................................................. 3.3 Oneopnic Properties.......................................................................... 3.4 Toxicodynamics..................... ......................................................... 3.4.J Uptake and Distribution.................................... ................ 3.4.2 Metabolism.......... .................................................................. 3.4.2.1 Relation between Chemical Structure. Reactivity and Mutatenic or Carcinogenic Effect.................. 3 .4 2.2 Metabolic Pathways................................................. 21 21 21 24 25 26 26 26 4 Clinical Spectrum.................................................................................................... 4. | The Triad: Raynaud's Phenomenon. Pseudoscicroderma and Acroosteolysis................................................................................................. 4.1.1 Familial and Idiopathic Acroosteoiysis............................................ 4.1.2 Epidemiology of Occupational Aeroaetcoiyss............................ . 4.1 J Clinical end Roentgenological Fearures........................................... 4.1.3.1 Occupational Acroosteolysis.............................................. 4.1 Pseudoscicroderma.............................................................. 4.J.4 Histology.............................................................................................. 4.1.4.1 Cutaneous Lesions................................................................ 4.1.4.2 Bone Lesions....................................................................... 4.1.5 Arteriography. CapOlaroscopy. Infrared Thermography............... 4. | .6 Immunological Studies....................................................................... 29 31 34 34 36 36 38 39 39 39 40 421 1 Department of Medicine. Director Prof. Dr. HJ. Dcnglcr. University of Bonn. KRG w K. Lelbach and H.J. Manteller Vinyl Chlonde-Assu.. 4 1 7 Pathogenetic Considerations............................................ 4.2 Non-malignant Liver Disease in Vinyl Chlocide/Poly vinyl Chloride Production Workers.............................................................................. 4.2.1 Clinical Manilestaiions oi Non-malignant Liver Disease . . 4.2.2 Laboratory Findings............................................................... 4.2.2 Gross Inspection oi the Liver and Spleen 4.2.4 Histology................................................................... 4.2.4.1 Hepatic Fibrosis......................................... ............. 4.2.4.2 Sinusoidal Lining Cells............................................ 4.2.4 J Hepatocytes.............................................................. 4.2.4.4 Histology of the Spleen.......................................... 4.2.5 Pathophysiology of Portal Hypertension............................. 4.2.6 FoUow-up of Non-malignant VCNt-induced Liver Disease . 4.3 Angiosarcoma of the Liver................................................................. 4.3.1 Epidemiology........................................................................... 4.3.2 Clinical Manifestations......................................................... 4.3 J Peritoneoscopy......................................................................... 4 J .4 Gross and Histological Morphology....................................... 4.3J Therapy. .................................................................................... 44 44 43 49 50 51 55e14i <4 54 55 57 57 57 74 76 78 SO one of the least harm)' later turned out. had r evaluation of acute efl to reveal its carcinoge;. might have continued ' place, considering that vapour phase unde: an*. reactive double-bond. Today vinyl chlond formation and data on cisely a quarter of a cei tributabie to this new c with the shocking disci. tion workers heavily ex Lng that the monomer t pound did not alert the 4.3.6 Risk Assessment...................................................................... 4.3.7 Mortality and Cancer Morbidity Studies............................. 4.4 Miscellaneous Aspects......................................................................... 4.4 i Thrombocytopenia and Platelet Function Tests................ 4.4.2 Central and Penpheral Nervous System................................ 4.4.3 Pulmonary Changes................................................................. 4.4,a Genetic Effects of VCM......................................................... SO SI 982 84 85 87 in workers engaged in ; tished in 1949 (Tribute- Ultimately, it was tl curred in workers expo a causal relationship: (J pseudosierodenna;(2) 5 Conclusion and Outlook............................................................................. 88 liver. Particularly, the J. nancy among a compar.: References........................................................................................................... 69 alarming experience wit a connection between V Key words: Acroosreolysis - Angiosarcoma of the Liver -- Portal Fibrosis and Portal Hypertension -- Pscudosclerodtrma - Raynaud's Phenomenon - Vinyl Chloride lungs or the gastrotnt*.: the prolonged latency p sarcoma of the liver, r-v these tw6 fatal consequ the conclusion that V;v 1 Introduction cancer meeting in Hous. to VCM was a very sen. It should be stresses The history ofvinyl chloride-associated disease, its recognition and prophylaxis is a precise, an intermediate classic example of shutting the stable door after the hone has bolted. It should help to mainly in the mammal, emphasize the need to shift our attention to preventing exposure from occurring rather mefixation products 0^ D than to reparative measures. In view of the large number of new and potentially hazard* ous chemicals introduced each year into the workplace and the environment, this ac cated from the polymer, they contain umacted - count should again alert us to the necessity of pretesting chemicals adequately for PVC (thermal decompo* r their potential health effects, even at the risk that technological progress will develop toxicity of pyrolysis prv- l. at a more modest rate. Large-scale production of the synthetic resin polyvinyl chloride (PVC), a thermo plastic material suitable for the most widely diversified industrial use. was begun around 1930 in the United States and in Germany. The monomer, vinyl chloride K N1 C mainly due to the relea.1 A bar 1969\Dyer and E; and only very small or n (OTlfara et ai. 1971 cite (VCM), a rather simple aliphatic compound, was believed until the early 1960s to be CO tu Li BFG09634 Mantriic: 49 50 51 5i < 54 55 57 57 74 "6 78 80 80 81 8i:2 8Si 3* 3S 8> / Ponei ~#Ui Jxcjiia ''uld help to irring rather TiaUy hazard* nt. this acuiy for .ill develop a thermobegun iloride - `>60* to be Vin> I ColonJe-4s<ocut4 Disease > one of the lea: harmful chlorinated hydrocarbons. Early animal experiments, a it later turned out. had indeed been earned out with dosages sufficiently high for the evaluation of acute effects, but chrome exposure had not been of sufficient duration co reveal tu carcinogenic properties. On purely heorericai grounds, however, one might have connnued to feel uneasy wuh this compound as a pollutant of the work place. considering that it is (li a halogenated hydrocarbon which f Z) exists in its vapour phase under ambient conditions finhalauve exposure) and i31 contains a highly reactive double-bond. Today vuiyl chtoride-tssoaated pathology is wU documented. A large body of in formation and dau on this topic has been accumulated, notably since 1974, but pre cisely a quarter of a century had to pass before the full range of symptomatology at* tnbutable to this new occupational health hazard became recognized in January 1974 with the shocking discovery that haemangiosarcoma of the liver occurred in produc tion workers heavily exposed to PVC. Early and not easily accessible reports suggest ing that the monomer might be an environmental risk for workers handling this com pound did not alert the experts sufficiently. The earliest indication of adverse effects in workers enpged in the production and processing of ?VC, a Russian study pub lished in 1949 (Tribukh et al. 1949), received little attention. Ultimately, it was the exceptional chancier of the three major lesions which oc curred in workers exposed to VCM that contributed most to the final appreciation of a causal relationship: (1) the syndrome of acroosteolysis, Raynaud's phenomenon and pscudosleroderma: (2) non-cirrhotic portal hypertension; and (3) angiosarcoma of the liver. Particularly, the discovery of a cluster of four cases of this extremely rare malig nancy among a comparatively small group of workers (Orec/i et ai. 1974a) was an alarming experience which ealled for immediate action. It can easily be imagined that a connection between VCM and the more common malignancies, such as cancer of me lungs or the gastrointestinal tract, might still have gone unnoticed. On the other hand, the prolonged latency periods of both non-curhode portal hypertension and angio sarcoma of the liver, roughly 10 and 20 yean respectively, delayed the recognition of these two fatal consequences of chronic exposure to VCM. But one can hardly escape the conclusion that Viola's discovery ofcancer in experimental animals, presented at a cancer meeting In Houston in 1970. was sufficient evidence to indicate that exposure to VCM was a very serious occupational hazard (Perm 1976). It should be stressed that the noxious agent is solely the monomer, or to be more precise, an intermediate of the monomer's metabolic bioactivation, which takes place mainly in the mammalian liver and yields certain highly reactive epoxides. The poly merization products (PVC), L** the solid plastic and the plastic consumer goods fabri cated from the polymer, are chemically inert articles which carry no health risk unless they contain uarescttd residual monomer. Even the combustion of snides made from PVC (thermal decomposition in fires) docs not yield free vinyl chloride monomer; the toxicity of pyrotytis products of potyvfeyt chloride polymers and formulations is mainly due to the release of hydrochloric add and carbon monoxide (Cornish and Abar l969iDytr zndteh 1976;Sortnjon 1976;Moser 1976: Cbferrfyn etaL 1976) and only very small or no quantities of phosgene derived from residual monomer (O'Man et al. 1971 dted by Colardyn et al. 1976). ***. ,4/Ft BFG09635 mi if r 4 2 Technological Details 2.1 Vinyl Chloride Monomer i VCM) W.K. Lelbach jnd H.J ManreMer At standard (ambient) conditions of temperature And pressure, vinyl chloride ICH; CHChchJoroethylene.chloroethene) is a non-tfriuting, colourless gas wuU a faintly sweet odour, inflammable at concentrations above 3.8% by volume a\ ji.\ which is only slightly soluble in water, soluble in ethyl alcohol and easily soluble in ether ami carbon tetrachloride. VCM is mainly used as an intermediate in the manufacture of plastics, as a refrigerant and in organic synthesis. It was formerly aho employed as a propellant for aerosoles. It is easily liquefied under pressure and is usually handled and shipped as a liquid. Caseous VCM condenses at --13.8*C and 760 Torr (* 10U kPa) to a colourless liquid of low viscosity (Le/aux 1966). Its physical properties are listed in Table 1, the most important of which are its low boiling point, its high specific grav ity (gaseous VCM is 2.15 times heavier than air), its low solubility in water and the half-life in air. ranging from 3 to 20 h. Table 1. Physical properties of VCM Mol. wi.: B.p.: F.p.: Flash point: Limits of flammability: AutoignitioR temperature: 62.503 *-l3.89C t--13.7 to -15.9) --153.7*C -78.5*C (Cleveland open cup) 3.5%--29.3% bv volume in air above --78.5 C (. 38 000-293 000 ppm) 4?2*C Vapour pressure: mm Hg 10 100 692 2300 -87.5 -SJ.8 -15.8 *20 2b60 * 25 Vapour density: 2.15 g/litre (calculated at 25*C and 760 mroHg (air* 1) Sp. ft. of liquid VCM: 0.9121 at -20*C/4*C 0.99 at --25*Cf4*C________________________ Sources: Fcirhall 1957;/nA \963.Zapp 1964-J,efeux I9b6:Ostermayer 19o7. Roubal 1972. 2.1.1 History The French chemist,Regnault (1835) was apparently the first to study systematically the synthesis and analysis of vinyl chloride. Liebig, who had done some earlier prelim inary experiments, encouraged Reptault to investigate this compound when Regnault spent several months in Liebig'% laboratories. All compounds containing the vinyl group (CH*CH--) polymerize readily (FairfiaU 1957). Spontaneous polymerization of vioyi chloride to a white opaque solid mass under the influence of sunlight was first described by Baumann in 1872; heaho quotesa paper by Soyner and Glinsky (who Vinyl CM- succeed^ izmg subsi 2.1.2 Pro. Large-scai by emplo\ 1) Convers CH=CH 2) Convers chloroe: ch; cr CHjCl- VCM vi Thus, any 1< tians in the in the rane (IARC 197when VC.V ntayer 196" in commer 1966; Dm-, In the ' conjecture-, retrieved Vi yses carriesum of all ii genatet)*., reacted mor in prepolyn the concern that even lr* methyl ehl: isobutane, n ference in p "T -- BFG09636 inj H J Nfjr*rtf-;rr 'I chloride (CH: * .is with a fainih :n air.*'hich s funic in ether and - manuuciure ot *<o employed as i usually handled md fort( 101-3 kPa) roperties ire listed i< high specific grav. ji water and the Vtf --73.5*C : 2300 M + 20 2660 * IS 'OmaKp t-rmgftr 1967; - Tiudy systematically ; some earlier prelim* otmd when Renault icining the vinyl .ms polymerization of -t' sDfdight was first - ami Glinsky (who Vin\l Cu!urtdc-A*ojtsd Di'cjw succeeded in decomposing vinyl chlonde co nionocliioroaJdciiyde with the ltd Of OXJJiZing subs'ances such as li> poclilorous jcia. 3.1.3 Production of VCM Large-scale commercial synthesis of VCM with a high yield was mads possible much later by empioymg two principle methods, the second having non largely replaced Use first: l) Conversion of acetylene to VCM by hydrochlortnation: CH^H + HQ -- CHj^HG (catalyst: HfCI; on charcoal) (.lurroi 1974) 3) Conversion of ethylene by vapour-phase or liquid-phase oxychlorutation to l .2-dichioroechane and subsequent pyrolysis (thermal cracking) to VCM {Albnpxt 1967a): CH:<H; 2HCIM.'2 0, - CH:G-CH-a + H,0; CH;Cl-CH:G 4a0*C^y10^^ CH;-CHG *KG pumice catalyst (pyrolysatthermai cracking,Aurrm 1974). VCM was usually manufactured in dosed systems and stored in outdoor tadiities. Tlius. any leakage of the gas was readily diluted in the ambient air. VCM concentre* lions in the atmosphere at some distance from manufacturing plants were found to be in the range 1-2 ppm. In close proximity, the concentration ranged up to 50 ppm (1ARC 1974). Spontaneous polymerization in light has also been repeatedly observed when VCM comes into contact with atmospheric air due to container leakage (Ostermover 1967). A prerequisite for the polymerization process is a high degree of purity in commercially produced VCM. Impurities retard the polymerization process (Lcfetx 1966; Ostamayer 1967). In the early discussion about the cause of vinyl chloride-associated disease it was conjectured that other compounds or impurities contained in prepolymerization or in retrieved VCM might have been the causative agentls) (ftrfes and I'ersen 1974). Anal yses carried out by rix West German manufacturers of PVC, however, showed that the sum of all impurities (such as saturated or unsaturated hydrocarbons and their halogenares) was 01)177 by volume for prepolymerization VCM and 0.1% for retrieved unreaeted monomer. Only methyl chloride was found in concentrations of 50--300 ppm in prepolymerization VCM and 100-500 ppm in retrieved VCM (in one instance only, the concentration ranged between 1000 and 3000 ppm). But it should be kept in mind that eves 1000 ppm methyl chloride in VCM would mean, at 500 ppm VCM in air. a methyl chloride concentration in air ofonly 0.5 ppm. All other impurities (propylene, tsobutane, /i4uone etc.) would then be in the ppb range. Besides, no significant dif ference in purity could be found between VCM from acetylene and from ethylene. 21108006 BFG09637 2.2 Production of Polyvinyl Chloride IPVC) W.K. LfiJbJth and H.J. 2-2.1 Technology of Polymerization The following description is meant to serve merely as a rough sketch of the procedures and technological details involved in (he production of polyvinyl chJonde. Vinyl chloride monomer is polymerized in large autoclaves (reactors) at remperatures between 40*C and SO'C and pressures of 6--16 (8--12) atmospheres. Th-re are usually several reactors (up to 10-30) located in one building. The reactivity of the monomer is a function of its double-bond. The second functional site of the vinyl chloride molecule, the chlorine atom, does not react easily. The double-bond of VCM is not only the site from which the polymerization originates but is also the source of the toxicity and carcinogenicity of this compound when it is being metabolized in the body. The polymerization of VCM, which is a strongly exothermic reaction {Struct 1976), is initiated with the aid of compounds soluble in VCM that form free radicals at relatively low temperatures. Initiators are such compounds as lauroyl peroxide, isopro pyl percarbonate, azo-bts-isobutyronitride, and others. The free radicals react with the double-bond of the monomer, transforming it in turn into a free radical and thus prop agating the growth of a chain of molecules with a terminal free radical. Chain growth is interrupted by saturation of the terminal free radical which often involves a reaction between two growing chains {Molten and Ziclhuis l964;</four 1966:Albnghr 1967 2-cfiominitisftaus 1972 .Slater 1972). The random character of such termination steps accounts for the production of chains of different length and hence different de grees of polymerization, with molecular weights of the finished PVC being statistically distributed around a mean value. Commercial PVC polymers have average molecular weights that vary from about 50 000 to !50 000daltons(4&fl!rA' 1967b). Degree and velocity of polymerization, which are influenced by temperature and the concentration of initiators, determine the specific type ofPVC produced {Jrny 1973). During polymerization considerable amounts of the monomer are at first dissolved in the polymer, but most of this is later also transformed to PVC as polymerization progresses. The polymer which is not sol uble in the liquid monomer precipitates out. The process of polymerization slows down towards the end of the reaction. It is terminated, depending on the method used, when approximately 80%--90% of VCM is polymerized. The timing of this termina tion of the process is essential for the physical properties of the resins produced. The heat generated during the exothermic process of polymerization must be removed to keep the temperature of the reaction under control. Mechanical agiution aids in trans ferring the heat across the colloidal system to the cooling jacket of the reactor. During the process of polymerization certain quantities of the polymer adhere to the walls of the reactor and form a slowly thickening continuous film or crust. This polymer crust on the inner surface of the reactor vessel, which contains cavities Ailed with unreacted monomer, impedes the conductance ofheat; it has, therefore, to be cleaned away after termination of the bateh process (Bama 1976). After completion of the polymerization process, the slurry is released from the re actor into a dump tank. Residual unreacted vinyl chloride monomer is partly solvated in the polymer (about 10%); the remainder is dispersed in the water phase or is present Vinyl Chlorde-' in the vapour ph. VC monomer is t is then punned b the finished poh and must diffuse Raw PVC resin, l1 (VKE 1975). Ap proximately 500 The slurry fro large enough to h are then pumped wet polymer, a er drying methods, i merization, yield; fine solid panicle drying temperatu; polymer. A cydo The solid polymer storage bins or *Lidried powder con 2.2.2 Methods o Four different inPVC {Frey 1973' Suspension Solyn which monomer (such as polyvini * conduction with b this method wh;. Emulsion Potym. was added in the except that large. are added. Emubemulsifiers cannc Bulk (Mass) Poly the additonof oil The first reactor second one is use. solid state, to ess<reaches a level of characterized by' good optical clan i H.J. Manteller >( the procedure? ride. >rs) at tempera* eres. There are activity of the of the vinyl le*boad of VCM >so the source of etaboozed in the action (Samn rm free radicals a: ' peroxide, isoproais react with the cal and thus prop* ti. Chain groweft cs olves a reaction ^'.AJbnght 1967 h termination cnee different debeing statistically jn from about poiymenzaf.m, determine `^n^ooBderable this is later uhicn is not sol* trzacon slows the method used, of this terrmnrns produced. The -u be removed to .ition aids in tnmhe reactor. During ere to the walls of i his polymer crust >cd with utueacted cleaned away after a*d from the rcT a partly solvated phase or is present Vinyl Chlonde*Associawd Disease T in the vapour phase above the slurry-. 'Vlule a batch is in rhe dump tank, this unreacted VC monomer is retrieved by pumping it off into a VCM storage tank. Retncved VCM is then purified by subsequent distillation for recycling purposes. Monomer solvated in liic finished polymer cannot easily be extracted since it has a strong affinity for PVC and must diffuse through the particles: tlus diffusion depends on time and temperature. Raw PVC resin, therefore, still contains certain quantities of unreacted monomer IVKE 19*5j. Barnes 11976> reported that the polymer in the slurry suU contains ap* proxrmately 500 ppm of vmyi chionde. The slurry from the dump tank u pumped into a storage tank (blend tank) which is large enough to hold several batches of the product. The contents of the blend tanic are then pumped into a centrifuge which separates the wee solids from the water. The wet polymer, a granular mass, is dried either in rotating tubular dryers or by spray* drying methods, the latter being used mainly for products formed by emulsion poly* menzanon. yielding a polymer which is similar to a very fine white flour. These very fine solid particles are fed directly into a spraydrying column without dewatering. The drying temperature should not exceed 60*C to prevent thermal decomposition of the polymer. A cyclon separator at the exit end of the dryers removes coarser particles. The solid polymer particles are then sized by multiple-layer screens, air-conveyed to storage bins or silos and finally packaged for shipment (Albright 1967d). The resultant dried powder contains about SO ppm of monomer (Same? 1976). 2.1.2 Methods of Polymerization Four different methods of polymerization are used for the commercial production of PVC (Frey 1973), the first two now being the most widely used: Suspension Polymerization. Polymerization is earned our in an aqueous system in which monomer droplets art maintained in suspension by means of protective colloids (such as polyvinyl alcohol, gelatin, substituted celluloses) under heat and pressure in conjucdon with brisk agitation. Reiiriveiy large polymer particles can be obtained by this method which `dry biend* well. Emulsion Polymerization is the oldest technique, to which suspension polymerization was added in the 1950s. The process is similar to that in suspension polymerization, except that large amounts of emulsifying agents (such as soaps or other surfactants) arc added. Emulsion polymerization yields resins of a very small particle size. The emulsifiers cannot be completely removed. Bttlk (Moss) Polymerization. In this proecss VCM is polymerized in two stages without the additon of other liquids. The two reactors are operated batch-wise and in series. The first reactor (a `prepolymefixer) provides for the Initial liquid phase. while the second one is used for agitating the slurry, which Is transformed, through a sticky solid state. to essentially dry particles until the conversion from monomer to polymer reaches a level of about 75%-SO%. The resins obtained by bulk polymerization are characterized by high purity and particle uniformity, resulting in an end-product of good optical clarity. I i i ;r ;! il saae&irz BFG09639 *'-J . _ m S W.K. Lvlbjvti jnJ H J 'laruiU-r Strlueto'i Polymerization. This type of precipitation polymerization is earned out in organic solvents such as 'i-butane or cyclohexane. It accounts for only a small percent age ot the toui amount of all PVC resins produced and it is used for the production of copolymers. Copolymers arc mixtures of comonomers (such as vinyl ace talc, vinylstearate. vinyiidene chloride, propylene, acrylonitrile etc.) and vinyl chloride. The co monomers tend to improve flexibility and limited solubility of the product in solvents and exert an influence on the temperatures required for compounding. 2.2J Compounding As a next step, depending on the end use, the dried polymer, a whitish powdery or granular product, is then compounded (or dry blended) under pressure at fusion tem perature with the aid of plasticizers (mainly phthalate ot other organic esters) and light and heat stabilizers (heavy metal salts, organotin compounds, and other stabilizers). Lubricants or dyes can be added. Plasticizers are added for the production of flexible PVC: rigid PVC contains little or no plasticizer. These additives can also be a source of toxicity. The plasticizers may slowly diffuse out of the final product depending on its compatibility. Lead-containing stabilizers may also pollute the working atmosphere (Smotcic 1966; Tola 1975). Compounding is carried out by hot mixing at fusion tem peratures below or within the softening range (120*C-- 16G*C). Diversified compound ing and processing technologies were developed aboui 1950. The compounded polymers are used for the production of diverse end-products. The final conversion of the thermoplastic PVC resins into consumer end-products is accomplished by such procedures as extruding, calendering, injection or compression moulding, blow moulding, dipping (coating) and hut spraying. Temperatures used in these processes range from 10Q*C to 300'C. End-products include a vast number of articles used in almost every sphere of daily life. The temperatures during the fabrica tion operations (compounding and conversion of compound polymer into consumer articles) drive off part of the small concentrations of residual monomer still contained in the polymer. Barnes (1976) calculated that the final fabricated articles contained approximately 5 ppm VCM and those for foodstuff packaging (bottles, films, foils) even less. 2.2.4 Sources of Exposure to VCM in PVC Production Both polymerization of VCM and subsequent processing (centrifuging, dry ing, screen ing. bagging) are usually earned out in closed buildings. Exceptions can be found in hot climates {Aryanpur 1977). Polymerization is of necessity a batch process that re quires a large number of single operations. Therefore, valves, gaskets, shaft-openings and control gear are subject to heavy wear and thus to leakage. Other sources of pollu tion of the working atmosphere are exchange of parts and repair jobs. Tire degree of pollution also depends to a large extent on the quality and effeetivity of monitoring equipment and special exhaust systems. Opening of autoclave vats for cleaning and control purposes resulted in larger spill-over of the tank atmosphere into the work en vironment. Numerous reports of workers with prenarcotic symptoms (dizziness etc.) Vinyl 1 i permit t' in the pr The: clave va: walls ('p tors, haj degassed and lar^-. were opr ed the fr. tion still manly, tl those wt(centrifu ties of - ventilattc shipmer.* nomer. v. are drive- Table 2. 1-ppr I m (Pei; 1 mg/hii I mg.m* 1 pptn XT- 223 T In the rv nant mon coven j (Le/aux I lect as 2 . opened . became k BFG09640 '.jrJtelttf mi m i percent- The co* volvents ry or run tem* i and light flexible source of >ig on its <7here in temnpound- ducts, nets :s "* "ion tvd in .!* *f - ncu- Vm>i CJii-?ndc*A*.v:jieJ Di'ea** permit the conclusion that episodes of acute overexposure to VCM were not rare events in the past. There is no doubt, however, that those workers who manually cleaned the auto* clave vats by scraping away or chipping off the poi> mar skin' tunned on the reactor walls Cpoi> cleaners'), and who tn the past had co spend several hours in<td< the reac tors. had been exposed to the highest concentrations of VCM. Although the vats were Jcgcise- prior to entry, unreacted monomer remained trapped m the polymer skin, and larger amounts of VCM were released when cavmes formed tn the polymer crust were opened by chipping. Use later introduction of automatic cleaning systems reduc ed the frequency of entry' into the reactors, but some manual cleaning of shorter dura tion still had to be done after every 20th-30th run. It is. therefore, plausible that, pri marily. Use most severe advene effects of exposure to VCM were fully recognized in those workers who had been employed m this job category. But the subsequent steps (centrifuging, drying, screening) also involve the release of some of the terser quanti ties of unreacted residual monomer from the panicles to pollute the environment if ventilation. notably of the drying facilities, is inadequate. Finished polymer, ready for shipment or subsequent compounding. still contains small quantities of unreacted mo nomer. which either slowly diffuse out and pollute the bagging areas during storage or are driven out by the high temperatures necessary for compounding. Table 2. Conventon cable for concentration of VCM in ambient air screenmd in that re* minsp f poilu^reeof Miorntg 5 and work en- i etc.) ctqsqttz BFG09641 10 W.K. Lelbacli and H.J Marsieller States *as almost completely destroyed when VCM escaping front a leak detonated {Albnjht 1967a). Another explosion in one of the two Rumanian factories operating at that time was mentioned by Suciu et al. (1975). Monitoring of VCM concentrations polluting the work environment was then directed largely towards preventing VCM from reaching the flammability limit. 2.2.6 The Odour Threshold Unfortunately, gaseous VCM has no irritating or unpleasant warning properties. Its mild odour is described as faintly pleasant, sweet or ethereal. Some of the PVC workers we interviewed reported that they had even enjoyed `sniffing the gas', which soon resulted in a feeling of light-headedness. For the early days of PVC production, when appropriately sensitive monitoring equipment was not yet available, workers' re* ports about perception of the odour of VCM can be taken as circumstantial evidence for a rough estimate of the actual degree of exposure. It should be kept in mind, how* ever, that in chemical production units the presence of other odoriferous chemicals and the possibility of olfactory fatigue, as well as different levels of individual sensitiv* ity. may render it very difficult to determine the factual odour threshold of a certain gaseous substance unless it possesses irritating warning properties. In \929,Schmidr andSchaumann declared that the faintly sweet gas is practically odourless at concentrations of 5%~10% by volume. Veltman and Lange (J977a. b) assumed an odour threshold of 5 000-10 000 ppm. Volunteers exposed to VCM detected a slight odour at 4 100 ppm; a distinct odour was noted at 6 600 ppm for 30 min and this was accompanied by subjective symptoms of dizziness and sleepiness (Irish 1963). Gehringet al. (1979) recently mentioned a threshold of approximately 3500 ppm. Others have claimed that a concentration of400--500 ppm is the lower limit for detection of VCM by its odour (Baretta et al. 1969; Cook et al. 1971 -.Marko witz et al. 197V.Lcfcvre 1975,cited by Hublct 1975). Baretta et al.(1969) conducted experiments with concentrations of 50.250 and 500 ppm in an exposure chamber, in which 13 volunteers participated. At 500 ppm only some of them chimed that they were able to detect the odour, but this was inconstant. Table 3 shows that differences between the various estimates are at least one order of magnitude. The close proximity between the perception of the odour of VCM and incipient CNS symptoms as reported by Irish (1963), however, makes it likely that the actual odour threshold ean be as* sumed at or above 4000 ppm. In contrast to VCM, the comonomer vinyl acetate, for instance, has distinct warn* ing properties and can be detected by its odour at a level as low as 0.4 ppm; eye and throat irritation begin upward of 5 ppm and are noted by all test subjects at a concen* trationofZ)^ ppm (Dees* and Joyner 1969). 2.2.7 VCM as an Anaesthetic Agent VCM was once even considered for use as an anaesthetic agent. In 1929. Schmids and Schoumonn speculated about using VCM as a supplementary narcotic at concentra tions of 3%--S% (v/v) ( 30 000--50 000 ppm) in combined nitrogen oxide oxygen Vinyl Chior; Table 3. Otfs- Lower limit . 5 000-10 Of 5 O' 4K 3 51 w|. 400--5v 40 40' anaesthesia be tic and lethal oxygen; cone.however, that eluded. In.to* 10* VCM to: several hours i commented u: mined about >. 3-5-5 mmol { mmol (244 0C Osreretal., in cardiotoxicity man because c like other hale amines (Iriih i the past for an. 2-2.8 Effects Some individu. listed in Table without acute * symptoms sue! adequate warm exposure to hi?; A 21-year-old . 10 min after en which had bee cardiac enlarge: have been acut. which occurred doubt that he:* found dead wk. BFG09642